Oncologists' non-verbal behavior and analog patients' recall of information.

Science.gov (United States)

Hillen, Marij A; de Haes, Hanneke C J M; van Tienhoven, Geertjan; van Laarhoven, Hanneke W M; van Weert, Julia C M; Vermeulen, Daniëlle M; Smets, Ellen M A

2016-06-01

Background Information in oncological consultations is often excessive. Those patients who better recall information are more satisfied, less anxious and more adherent. Optimal recall may be enhanced by the oncologist's non-verbal communication. We tested the influence of three non-verbal behaviors, i.e. eye contact, body posture and smiling, on patients' recall of information and perceived friendliness of the oncologist. Moreover, the influence of patient characteristics on recall was examined, both directly or as a moderator of non-verbal communication. Material and methods Non-verbal communication of an oncologist was experimentally varied using video vignettes. In total 194 breast cancer patients/survivors and healthy women participated as 'analog patients', viewing a randomly selected video version while imagining themselves in the role of the patient. Directly after viewing, they evaluated the oncologist. From 24 to 48 hours later, participants' passive recall, i.e. recognition, and free recall of information provided by the oncologist were assessed. Results Participants' recognition was higher if the oncologist maintained more consistent eye contact (β = 0.17). More eye contact and smiling led to a perception of the oncologist as more friendly. Body posture and smiling did not significantly influence recall. Older age predicted significantly worse recognition (β = -0.28) and free recall (β = -0.34) of information. Conclusion Oncologists may be able to facilitate their patients' recall functioning through consistent eye contact. This seems particularly relevant for older patients, whose recall is significantly worse. These findings can be used in training, focused on how to maintain eye contact while managing computer tasks.

The relationship between oncologists and peripheral hospital radiologists in the north-west of England

International Nuclear Information System (INIS)

Bungay, Peter M.; Carrington, Bernadette M.; Corgie, Delphine; Eardley, Anne

2002-01-01

AIM: To audit the relationship between Cancer Centre oncologists visiting peripheral hospitals and peripheral hospital radiologists by assessing (i) oncologists' knowledge of local radiological services; (ii) oncologists' perceptions of peripheral radiological services; (iii) peripheral radiologist's perceptions of oncologists; (iv) barriers to communication. MATERIALS AND METHODS: A postal questionnaire was sent to all radiology departments visited by an oncologist, and to all medical and clinical oncologists from two regional oncology centres. RESULTS: The response rate was 100% (21 peripheral hospital radiology departments and all 35 oncologists). (i) Oncologists' knowledge of peripheral hospital imaging modalities was limited (especially MRI and intervention). (ii) 72% of oncologists rated the peripheral hospital radiology service as excellent or good, 46% rated the radiology report quality excellent to good. Deficiencies in oncological reports were identified. (iii) 44% of radiologists thought the oncologist did not relate well with the local radiology department. 50% of radiologists did not know the visiting oncologist's specialist interest. (iv) 69% of oncologists did not regularly attend peripheral hospital clinico-radiological meetings. Lack of written and oral information was hampering both specialities. CONCLUSION: Communication between oncologists and the local radiology department should include: (1) information about local radiology services for visiting oncologists (including trainees) and on the oncology team for radiologists; (2) standardized report content; (3) improved clinical information for radiologists; (4) regular clinico-radiological meetings. Bungay, P.M. et al. (2002)

Community Oncologists' Decision-Making for Treatment of Older Patients With Cancer.

Science.gov (United States)

Mohile, Supriya G; Magnuson, Allison; Pandya, Chintan; Velarde, Carla; Duberstein, Paul; Hurria, Arti; Loh, Kah Poh; Wells, Megan; Plumb, Sandy; Gilmore, Nikesha; Flannery, Marie; Wittink, Marsha; Epstein, Ronald; Heckler, Charles E; Janelsins, Michelle; Mustian, Karen; Hopkins, Judith O; Liu, Jane; Peri, Srihari; Dale, William

2018-03-01

Background: This study's objectives were to describe community oncologists' beliefs about and confidence with geriatric care and to determine whether geriatric-relevant information influences cancer treatment decisions. Methods: Community oncologists were recruited to participate in 2 multisite geriatric oncology trials. Participants shared their beliefs about and confidence in caring for older adults. They were also asked to make a first-line chemotherapy recommendation (combination vs single-agent vs no chemotherapy) for a hypothetical vignette of an older patient with advanced pancreatic cancer. Each oncologist received one randomly chosen vignette that varied on 3 variables: age (72/84 years), impaired function (yes/no), and cognitive impairment (yes/no). Other patient characteristics were held constant. Logistic regression models were used to identify associations between oncologist/vignette-patient characteristics and treatment decisions. Results: Oncologist response rate was 61% (n=305/498). Most oncologists agreed that "the care of older adults with cancer needs to be improved" (89%) and that "geriatrics training is essential" (72%). However, decision to treat: younger age (adjusted odds ratio [aOR], 5.01; 95% CI, 2.73-9.20), normal cognition (aOR, 5.42; 95% CI, 3.01-9.76), and being functionally intact (aOR, 3.85; 95% CI, 2.12-7.00). Accounting for all vignettes across all scenarios, 161 oncologists (52%) said they would offer chemotherapy. All variables were independently associated with prescribing single-agent over combination chemotherapy (older age: aOR, 3.22; 95% CI 1.43-7.25, impaired cognition: aOR, 3.13; 95% CI, 1.36-7.20, impaired function: aOR, 2.48; 95% CI, 1.12-5.72). Oncologists' characteristics were not associated with decisions about providing chemotherapy. Conclusion: Geriatric-relevant information, when available, strongly influences community oncologists' treatment decisions. Copyright © 2018 by the National Comprehensive Cancer Network.

Responding to family requests for nondisclosure: the impact of oncologists' cultural background.

Science.gov (United States)

Chittem, Mahati; Butow, Phyllis

2015-01-01

Nondisclosure of cancer diagnosis is common in many Eastern countries. Consequently, immigrant families often approach oncologists with requests for nondisclosure in Western countries. To explore differences in the attitudes and practices of Western-born and nonWestern born oncologists in Australia when faced with a nondisclosure request. Using a cross-sectional design, oncologists were interviewed over the telephone. Using the snowball method, 14 Australian (Western = 9, non-Western = 5) oncologists were recruited. Oncologists participated in a semi-structured interview exploring their experiences of, and response to, a request for nondisclosure, and their perceptions of how their cultural background influenced these attitudes and responses. The interviews were transcribed and analyzed using interpretative phenomenological analysis. Six main themes emerged from the study: (1) Barriers to truthful communication, (2) an ethical and moral dilemma, (3) high costs of nondisclosure, (4) cultural influences on interpretation and understanding of requests for nondisclosure, (5) emotional impact of bad news on patients, families and oncologists, and (6) truthful disclosure as a gentle balancing act. All oncologists felt that the family request for nondisclosure was difficult, with many cultural and emotional nuances to take into consideration. Some immigrant Australian oncologists who had a similar cultural background as the patient/family, felt they could better understand the desire for nondisclosure. Irrespective of their cultural background, all oncologists acknowledged that breaking bad news had to be done in a gentle, gradual manner. The study suggests a need to develop a culturally sensitive cancer communication model.

Experiences and attitudes of Dutch rheumatologists and oncologists with regard to their patients' health-related Internet use

NARCIS (Netherlands)

Kraan, C.F.; Drossaert, Constance H.C.; Taal, Erik; Smit, Willem A.; Seydel, E.R.; van de Laar, Mart A F J

2010-01-01

The objective of this study is to explore the experiences and attitudes of rheumatologists and oncologists with regard to their patients’ health-related Internet use. In addition, we explored how often physicians referred their patients to health-related Internet sites. We sent a questionnaire to

Evaluation of the Relative Citation Ratio, a New National Institutes of Health-Supported Bibliometric Measure of Research Productivity, among Academic Radiation Oncologists.

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Rock, Calvin B; Prabhu, Arpan V; Fuller, C David; Thomas, Charles R; Holliday, Emma B

2018-03-01

Publication metrics are useful in evaluating academic faculty for awarding grants, recruitment, and promotion. A new metric, the relative citation ratio (RCR), was recently released by the National Institutes of Health (NIH); however, no benchmark data yet exist. We sought to create benchmark data for physician faculty in academic radiation oncology (RO) and analyze correlations associated with increased academic productivity. Citation database searches were performed for all US radiation oncologists affiliated with academic RO programs. Gender, NIH funding, career duration, academic rank, RCR, and weighted RCR were collected for each faculty. RCR and weighted RCR were calculated and compared between each subgroup of interest. RCR percentiles were also created for reference. A total of 1,299 RO physician faculty members from 75 institutions were included in the analysis. Overall, RO physician were very productive and influential with a mean RCR of 1.57 ± 1.53 SD and median RCR (interquartile range) of 1.32 (0.87-1.94). Academic rank, career duration, and NIH funding were associated with increased mean RCR and weighted RCR. Male gender and having a PhD were associated with an increased weighted RCR but not an increased mean RCR. Current academic radiation oncologists have a high mean RCR value relative to the benchmark NIH RCR value of 1. All subgroups analyzed had an RCR value above 1 with professor or chair and previous NIH funding having the highest RCR and weighted RCR values overall. These data may be useful for self-evaluation of ROs as well as evaluation of faculty by institutional and departmental leaders. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Oncologists' negative attitudes towards expressing emotion over patient death and burnout.

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Granek, Leeat; Ben-David, Merav; Nakash, Ora; Cohen, Michal; Barbera, Lisa; Ariad, Samuel; Krzyzanowska, Monika K

2017-05-01

The aims of this study were to examine the relationship between negative attitudes towards expressing emotion following patient death and burnout in oncologists and to explore oncologists' preferences for institutional interventions to deal with patient death. The participants included a convenience sample of 177 oncologists from Israel and Canada. Oncologists completed a questionnaire package that included a sociodemographic survey, a burnout measure, a survey assessing negative attitudes towards expressing emotion, and a survey assessing desired interventions to cope with patient death. To examine the association between burnout and negative attitudes while controlling for the effect of sociodemographic variables, a hierarchical linear regression was computed. Higher burnout scores were related to higher negative attitudes towards perceived expressed emotion (partial r = .25, p training) helpful in coping with patient death. Our findings suggest that high burnout scores are associated with negative attitudes towards expressing emotion and that there is a wide variation in oncologist preferences in coping with patient death. Institutions should promote interventions that are varied and that focus on the needs of oncologists in order to reduce burnout. Interventions that legitimize expression of emotion about patient death may be useful. Another way to reduce stigma would be to require oncologists to "opt out" rather than "opt in" to accessing a selection of social and/or individual interventions.

Coordination of Breast Cancer Care Between Radiation Oncologists and Surgeons: A Survey Study

International Nuclear Information System (INIS)

Jagsi, Reshma; Abrahamse, Paul; Morrow, Monica; Hamilton, Ann S.; Graff, John J.; Katz, Steven J.

2012-01-01

Purpose: To assess whether radiation oncologists and surgeons differ in their attitudes regarding the local management of breast cancer, and to examine coordination of care between these specialists. Methods and Materials: We surveyed attending surgeons and radiation oncologists who treated a population-based sample of patients diagnosed with breast cancer in metropolitan Detroit and Los Angeles. We identified 419 surgeons, of whom 318 (76%) responded, and 160 radiation oncologists, of whom 117 (73%) responded. We assessed demographic, professional, and practice characteristics; challenges to coordinated care; and attitudes toward management in three scenarios. Results: 92.1% of surgeons and 94.8% of radiation oncologists indicated access to a multidisciplinary tumor board. Nevertheless, the most commonly identified challenge to radiation oncologists, cited by 27.9%, was failure of other providers to include them in the treatment decision process early enough. Nearly half the surgeons (49.7%) stated that few or almost none of the breast cancer patients they saw in the past 12 months had consulted with a radiation oncologist before undergoing definitive surgery. Surgeons and radiation oncologists differed in their recommendations in management scenarios. Radiation oncologists were more likely to favor radiation than were surgeons for a patient with 3/20 lymph nodes undergoing mastectomy (p = 0.03); surgeons were more likely to favor more widely clear margins after breast conservation than were radiation oncologists (p = 0.001). Conclusions: Despite the widespread availability of tumor boards, a substantial minority of radiation oncologists indicated other providers failed to include them in the breast cancer treatment decision-making process early enough. Earlier inclusion of radiation oncologists may influence patient decisions, and interventions to facilitate this should be considered.

Coordination of Breast Cancer Care Between Radiation Oncologists and Surgeons: A Survey Study

Energy Technology Data Exchange (ETDEWEB)

Jagsi, Reshma, E-mail: rjagsi@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States); Abrahamse, Paul [Department of Internal Medicine, University of Michigan, Ann Arbor, MI (United States); Morrow, Monica [Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Hamilton, Ann S. [Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA (United States); Graff, John J. [Department of Radiation Oncology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ (United States); Katz, Steven J. [Department of Internal Medicine, Division of General Medicine and Department of Health Management and Policy, School of Public Health, University of Michigan Health System, Ann Arbor, MI (United States)

2012-04-01

Purpose: To assess whether radiation oncologists and surgeons differ in their attitudes regarding the local management of breast cancer, and to examine coordination of care between these specialists. Methods and Materials: We surveyed attending surgeons and radiation oncologists who treated a population-based sample of patients diagnosed with breast cancer in metropolitan Detroit and Los Angeles. We identified 419 surgeons, of whom 318 (76%) responded, and 160 radiation oncologists, of whom 117 (73%) responded. We assessed demographic, professional, and practice characteristics; challenges to coordinated care; and attitudes toward management in three scenarios. Results: 92.1% of surgeons and 94.8% of radiation oncologists indicated access to a multidisciplinary tumor board. Nevertheless, the most commonly identified challenge to radiation oncologists, cited by 27.9%, was failure of other providers to include them in the treatment decision process early enough. Nearly half the surgeons (49.7%) stated that few or almost none of the breast cancer patients they saw in the past 12 months had consulted with a radiation oncologist before undergoing definitive surgery. Surgeons and radiation oncologists differed in their recommendations in management scenarios. Radiation oncologists were more likely to favor radiation than were surgeons for a patient with 3/20 lymph nodes undergoing mastectomy (p = 0.03); surgeons were more likely to favor more widely clear margins after breast conservation than were radiation oncologists (p = 0.001). Conclusions: Despite the widespread availability of tumor boards, a substantial minority of radiation oncologists indicated other providers failed to include them in the breast cancer treatment decision-making process early enough. Earlier inclusion of radiation oncologists may influence patient decisions, and interventions to facilitate this should be considered.

Nature of Medical Malpractice Claims Against Radiation Oncologists

Energy Technology Data Exchange (ETDEWEB)

Marshall, Deborah; Tringale, Kathryn [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Connor, Michael [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); University of California Irvine School of Medicine, Irvine, California (United States); Punglia, Rinaa [Department of Radiation Oncology, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Recht, Abram [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts (United States); Hattangadi-Gluth, Jona, E-mail: jhattangadi@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States)

2017-05-01

Purpose: To examine characteristics of medical malpractice claims involving radiation oncologists closed during a 10-year period. Methods and Materials: Malpractice claims filed against radiation oncologists from 2003 to 2012 collected by a nationwide liability insurance trade association were analyzed. Outcomes included the nature of claims and indemnity payments, including associated presenting diagnoses, procedures, alleged medical errors, and injury severity. We compared the likelihood of a claim resulting in payment in relation to injury severity categories (death as referent) using binomial logistic regression. Results: There were 362 closed claims involving radiation oncology, 102 (28%) of which were paid, resulting in $38 million in indemnity payments. The most common alleged errors included “improper performance” (38% of closed claims, 18% were paid; 29% [$11 million] of total indemnity), “errors in diagnosis” (25% of closed claims, 46% were paid; 44% [$17 million] of total indemnity), and “no medical misadventure” (14% of closed claims, 8% were paid; less than 1% [$148,000] of total indemnity). Another physician was named in 32% of claims, and consent issues/breach of contract were cited in 18%. Claims for injury resulting in death represented 39% of closed claims and 25% of total indemnity. “Improper performance” was the primary alleged error associated with injury resulting in death. Compared with claims involving death, major temporary injury (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.29-5.85, P=.009), significant permanent injury (OR 3.1, 95% CI 1.48-6.46, P=.003), and major permanent injury (OR 5.5, 95% CI 1.89-16.15, P=.002) had a higher likelihood of a claim resulting in indemnity payment. Conclusions: Improper performance was the most common alleged malpractice error. Claims involving significant or major injury were more likely to be paid than those involving death. Insights into the nature of liability claims against

ONCOLOGISTS' BARRIERS AND FACILITATORS FOR ONCOTYPE DX USE: QUALITATIVE STUDY.

Science.gov (United States)

Roberts, Megan C; Bryson, Amy; Weinberger, Morris; Dusetzina, Stacie B; Dinan, Michaela A; Reeder-Hayes, Katherine; Wheeler, Stephanie B

2016-01-01

Oncotype DX (ODX), a tumor gene profiling test, has been incorporated into clinical guidelines to aid in adjuvant chemotherapy decision making for early-stage, hormone receptor positive breast cancer patients. Despite United States (U.S.) guidelines, less than half of eligible women receive testing. Reasons for low usage are unclear: Our objective was to better understand U.S. oncologists' ODX uptake and how they use ODX during adjuvant chemotherapy decision making. We conducted semi-structured, ~30-minute phone interviews with medical and surgical oncologists in one U.S. State using purposive sampling. Oncologists were included if they saw greater than or equal to five breast cancer patients per week. Recruitment ended upon thematic saturation. Interviews were recorded, transcribed, and double-coded using template analysis. During analysis, themes emerged across three domains. First, organizational factors (i.e., departmental structure, ODX marketing, and medical/insurance guidelines) influenced ease of ODX use. Second, oncologists referenced the influence of interpersonal factors (e.g., normative beliefs and peer use of ODX) over their own practices and recommendations. Third, intrapersonal factors (e.g., oncologist attitudes, perceived barriers, and research gaps) were discussed: although oncologists largely held positive attitudes about ODX, they reported challenges with interpreting intermediate scores for treatment decisions and explaining test results to patients. Finally, oncologists identified several research gaps. As more tumor gene profiling tests are incorporated into cancer care for treatment decision making, it is important to understand their use in clinical practice. This study identified multi-level factors that influence ODX uptake into clinical practice, providing insights into facilitators and modifiable barriers that can be leveraged for improving ODX uptake to aid treatment decision making.

ROS Hexapod

Science.gov (United States)

Davis, Kirsch; Bankieris, Derek

2016-01-01

As an intern project for NASA Johnson Space Center (JSC), my job was to familiarize myself and operate a Robotics Operating System (ROS). The project outcome converted existing software assets into ROS using nodes, enabling a robotic Hexapod to communicate to be functional and controlled by an existing PlayStation 3 (PS3) controller. Existing control algorithms and current libraries have no ROS capabilities within the Hexapod C++ source code when the internship started, but that has changed throughout my internship. Conversion of C++ codes to ROS enabled existing code to be compatible with ROS, and is now controlled using an existing PS3 controller. Furthermore, my job description was to design ROS messages and script programs that enabled assets to participate in the ROS ecosystem by subscribing and publishing messages. Software programming source code is written in directories using C++. Testing of software assets included compiling code within the Linux environment using a terminal. The terminal ran the code from a directory. Several problems occurred while compiling code and the code would not compile. So modifying code to where C++ can read the source code were made. Once the code was compiled and ran, the code was uploaded to Hexapod and then controlled by a PS3 controller. The project outcome has the Hexapod fully functional and compatible with ROS and operates using the PlayStation 3 controller. In addition, an open source software (IDE) Arduino board will be integrated into the ecosystem with designing circuitry on a breadboard to add additional behavior with push buttons, potentiometers and other simple elements in the electrical circuitry. Other projects with the Arduino will be a GPS module, digital clock that will run off 22 satellites to show accurate real time using a GPS signal and an internal patch antenna to communicate with satellites. In addition, this internship experience has led me to pursue myself to learn coding more efficiently and

The Effects of Interruptions on Oncologists' Patient Assessment and Medication Ordering Practices

Directory of Open Access Journals (Sweden)

Patricia L. Trbovich

2013-01-01

Full Text Available Interruptions are causal factors in medication errors. Although researchers have assessed the nature and frequency of interruptions during medication administration, there has been little focus on understanding their effects during medication ordering. The goal of this research was to examine the nature, frequency, and impact of interruptions on oncologists' ordering practices. Direct observations were conducted at a Canadian cancer treatment facility to (1 document the nature, frequency, and timing of interruptions during medication ordering, and (2 quantify the use of coping mechanisms by oncologists. On average, oncologists were interrupted 17 % of their time, and were frequently interrupted during safety-critical stages of medication ordering. When confronted with interruptions, oncologists engaged/multitasked more often than resorting to deferring/blocking. While some interruptions are necessary forms of communication, efforts must be made to reduce unnecessary interruptions during safety-critical tasks, and to develop interventions that increase oncologists' resiliency to inevitable interruptions.

Negative emotions in cancer care: do oncologists' responses depend on severity and type of emotion?

Science.gov (United States)

Kennifer, Sarah L; Alexander, Stewart C; Pollak, Kathryn I; Jeffreys, Amy S; Olsen, Maren K; Rodriguez, Keri L; Arnold, Robert M; Tulsky, James A

2009-07-01

To examine how type and severity of patients' negative emotions influence oncologists' responses and subsequent conversations. We analyzed 264 audio-recorded conversations between advanced cancer patients and their oncologists. Conversations were coded for patients' expressions of negative emotion, which were categorized by type of emotion and severity. Oncologists' responses were coded as using either empathic language or blocking and distancing approaches. Patients presented fear more often than anger or sadness; severity of disclosures was most often moderate. Oncologists responded to 35% of these negative emotional disclosures with empathic language. They were most empathic when patients presented intense emotions. Responding empathically to patients' emotional disclosures lengthened discussions by an average of only 21s. Greater response rates to severe emotions suggest oncologists may recognize negative emotions better when patients express them more intensely. Oncologists were least responsive to patient fear and responded with greatest empathy to sadness. Oncologists may benefit from additional training to recognize negative emotions, even when displayed without intensity. Teaching cancer patients to better articulate their emotional concerns may also enhance patient-oncologist communication.

Audit with feedback (AWF) as a CME tool for radiation oncologists (ROs): evaluation of efficacy, perception, and cost-effectiveness

International Nuclear Information System (INIS)

Shakespeare, T.P.; Mukherjee, R.K.; Lu, J.J.; Wynne, C.J.; Back, M.F.

2003-01-01

Meta-analyses demonstrate Audit with Feedback (AWF) is effective CME, however educational efficacy for ROs is unknown. We evaluated an AWF CME intervention for ROs, determining efficacy, cost-effectiveness and participant satisfaction. CME program: CME incorporated fortnightly random patient chart audit, scoring management adequacy via checklist. Scores were presented at a same-day institutional meeting, and case management discussed. Senior peers provided educational feedback. RO behavior/performance was evaluated via chart review of new patients seen 2 months before commencement of CME (T0), and after 12 months of CME (T1). A validated instrument scored 19 items as '0' (inadequate/inappropriate) or '1' (adequate/appropriate). Comparisons of mean point-score for 10 behaviour items targeted by the CME AWF checklist, 3 non-targeted behaviour items, and 6 performance items were made; also percent charts achieving a '1' for each item at T0 and T1. A 14-item participant questionnaire measured satisfaction before and after efficacy results were known. Responses scored from 0 (very dissatisfied) to 5 (very satisfied), then averaged. Annual cost and cost-per-point gained incorporated salaries of organizers/ participants, and consumables. 113 and 118 charts were evaluated at T0 and T1. Mean score of targeted behavior improved between T0 and T1 (8.7 to 9.2 out of 10,p=0.0001), with no significant improvement for non-targeted behavior/performance items. Improvement occurred for 'Decision for treatment' (non-targeted; percent charts scoring '1' increased from 84% to 92%,p=0.08), and targeted items 'Letter to referrer' (53% to 66%,p=0.04), 'Treatment intent' (54 to 77%,p=0.0002), 'Laterality doublet' (91 to 98%, p=0.04), and 'Isodose-plan signed' (94 to 100%,p=0.006). Improvements varied between ROs. Participant satisfaction was positive, increasing from 3.2 to 3.7 after efficacy result distribution (p=0.0001). Annual costs and cost-per-point gained were $AUD13,820 and $27

Satisfaction with work-life balance and the career and retirement plans of US oncologists.

Science.gov (United States)

Shanafelt, Tait D; Raymond, Marilyn; Kosty, Michael; Satele, Daniel; Horn, Leora; Pippen, John; Chu, Quyen; Chew, Helen; Clark, William Benton; Hanley, Amy E; Sloan, Jeff; Gradishar, William J

2014-04-10

To evaluate satisfaction with work-life balance (WLB) and career plans of US oncologists. The American Society of Clinical Oncology conducted a survey of US oncologists evaluating satisfaction with WLB and career plans between October 2012 and March 2013. The sample included equal numbers of men and women from all career stages. Of 2,998 oncologists contacted, 1,490 (49.7%) returned surveys. From 1,117 oncologists (37.3% of overall sample) completing full-length surveys, we evaluated satisfaction with WLB and career plans among the 1,058 who were not yet retired. The proportion of oncologists satisfied with WLB (n = 345; 33.4%) ranked lower than that reported for all other medical specialties in a recent national study. Regarding career plans, 270 oncologists (26.5%) reported a moderate or higher likelihood of reducing their clinical work hours in the next 12 months, 351 (34.3%) indicated a moderate or higher likelihood of leaving their current position within 24 months, and 273 (28.5%) planned to retire before 65 years of age. Multivariable analyses found women oncologists (odds ratio [OR], 0.458; P hour, 0.977; P work hours and leave current position on multivariable analysis. Satisfaction with WLB among US oncologists seems lower than for other medical specialties. Dissatisfaction with WLB shows a strong relationship with plans to reduce hours and leave current practice. Given the pending US oncologist shortage, additional studies exploring interactions among WLB, burnout, and career satisfaction and their impact on career and retirement plans are warranted.

Closing the patient-oncologist communication gap: a review of historic and current efforts.

Science.gov (United States)

Pham, A Khoa; Bauer, Marianne T; Balan, Stefan

2014-03-01

Effective communication is essential in developing any relationship--this is particularly true between oncologists and their patients. The patient-oncologist relationship is one of the most delicate in medicine, and given the strong emotions associated with cancer, successful communication plays a paramount role in the wellbeing of patients and oncologists. Significant advances to close the communication gap have occurred over the past several decades, largely by addressing deficiencies in the various stages of an oncologist's lengthy training: undergraduate medical education, residency and fellowship, and continuing medical education. Stemming from several milestones achieved by highly motivated groups of individuals, including the creation of consensus statements and guidelines by communication education experts, progress has been made to improve patient-oncologist communication. This progress is marked by the development of evidence-based communication skills training programs, such as Oncotalk and Comskil, in addition to the creation of distant-learning modalities, such as the Studying Communication in Oncologist-Patient Encounters trial. This review article outlines the history of communication education during medical education and training, and brings to light more recent efforts to promote competent, communication-minded physicians necessary for effective cancer care.

Oncologists' strategies and barriers to effective communication about the end of life.

Science.gov (United States)

Granek, Leeat; Krzyzanowska, Monika K; Tozer, Richard; Mazzotta, Paolo

2013-07-01

Communicating about the end of life with patients has been reported as one of the most difficult and stressful part of the work of oncologists. Despite this fact, oncologists receive little training in this area, and many do not communicate effectively with patients. The purpose of this analysis, part of a larger study examining oncologists' experiences of patient loss, was to explore oncologists' communication strategies and communication barriers when discussing end-of-life issues with patients. Twenty oncologists were interviewed at three hospitals about their communication strategies on end-of-life issues with patients. The data were analyzed using the grounded theory method. The findings revealed the strategies to effective communication about the end of life included: being open and honest; having ongoing, early conversations; communicating about modifying treatment goals; and balancing hope and reality. Barriers to implementing these strategies fell broadly into three domains, including physician factors, patient factors, and institutional factors. Physician factors included difficulty with treatment and palliation, personal discomfort with death and dying, diffusion of responsibility among colleagues, using the "death-defying mode," lack of experience, and lack of mentorship. Patient factors included, patients and/or families being reluctant to talk about the end of life, language barriers, and younger age. Institutional factors included stigma around palliative care, lack of protocol about end-of-life issues; and lack of training for oncologists on how to talk with patients about end-of-life issues. We conclude by drawing implications from our study and suggest that further research and intervention are necessary to aid oncologists in achieving effective communication about end-of-life issues.

Education of Radiation Oncologists. Chapter 15

International Nuclear Information System (INIS)

Rosenblatt, E.; Leer, J.W.; Haffty, B.

2017-01-01

The availability of trained staff in adequate numbers is one of the main obstacles to the development of modern radiotherapy in developing countries. While radiation oncologists practising in affluent environments may not be aware of this reality, limited number of positions, low wages, limited access to sources of evidence and ‘brain drain’ are common in countries with limited resources. Epidemiological predictions of an increase in the crude incidence of cancer that will affect predominantly developing countries represent an alarming situation in which the countries that will face the steepest increase are those most poorly prepared to cope with it. Modern cancer radiotherapy is characterized by team work in which different professionals have different roles and responsibilities. The radiation oncologist is the physician who has been trained to participate in diagnosis, staging, prescription of the radiotherapy dose and patient follow-up.

Overcoming communication challenges in integrative supportive cancer care: The integrative physician, the psycho-oncologist, and the patient.

Science.gov (United States)

Ben-Arye, Eran; Shavit, Efrat; Wiental, Haya; Schiff, Elad; Agour, Olga; Samuels, Noah

2016-12-01

Complementary/integrative medicine (CIM) services are increasingly being integrated into conventional supportive cancer care, presenting a number of challenges to communication between healthcare professionals (HCPs). The purpose of the present study was to explore the impact of the communication between integrative physicians (IPs) trained in CIM and social workers (SWs) working as psycho-oncologists in the same oncology setting. We examine whether IP-SW communication correlates with the number of patient-SW sessions, as provided within the oncology department. SW-IP communication, defined as a summary of the IP consultation sent to the patient's SW, was compared to SW-patient communication, defined as the number of psycho-oncology treatment sessions. Of 344 patients referred by their oncology HCP for IP consultation, 91 were referred by an SW and 253 by an oncologist or nurse. IP-to-SW summaries were provided for 150 patients referred by a non-SW HCP (43.6%), and for 91 of SW-referred patients (26.5%). In all, 32 patients referred to the IP had no psycho-oncology interaction with an SW; 58 only one meeting; and 254 with ≥2 interactions, with 119 having >6 sessions. SW-patient interactions were greater with higher rates of IP-SW communication, for both patients referred by an SW (79.1%) and those referred by a non-SW HCP (77.3%) when compared to patients for whom no summary was provided (64.1%; p= 0.02). A greater level of IP-SW communication, measured by the provision of an IP summary to the patient's SW, was found to correlate with a higher rate of SW-patient interactions. The use of a structured two-way referral-summary between IPs and SWs has the potential to advance the SW-patient psycho-oncology interaction, within an integrative supportive cancer care setting. Copyright © 2016 Elsevier Ltd. All rights reserved.

How Radiation Oncologists Would Disclose Errors: Results of a Survey of Radiation Oncologists and Trainees

International Nuclear Information System (INIS)

Evans, Suzanne B.; Yu, James B.; Chagpar, Anees

2012-01-01

Purpose: To analyze error disclosure attitudes of radiation oncologists and to correlate error disclosure beliefs with survey-assessed disclosure behavior. Methods and Materials: With institutional review board exemption, an anonymous online survey was devised. An email invitation was sent to radiation oncologists (American Society for Radiation Oncology [ASTRO] gold medal winners, program directors and chair persons of academic institutions, and former ASTRO lecturers) and residents. A disclosure score was calculated based on the number or full, partial, or no disclosure responses chosen to the vignette-based questions, and correlation was attempted with attitudes toward error disclosure. Results: The survey received 176 responses: 94.8% of respondents considered themselves more likely to disclose in the setting of a serious medical error; 72.7% of respondents did not feel it mattered who was responsible for the error in deciding to disclose, and 3.9% felt more likely to disclose if someone else was responsible; 38.0% of respondents felt that disclosure increased the likelihood of a lawsuit, and 32.4% felt disclosure decreased the likelihood of lawsuit; 71.6% of respondents felt near misses should not be disclosed; 51.7% thought that minor errors should not be disclosed; 64.7% viewed disclosure as an opportunity for forgiveness from the patient; and 44.6% considered the patient's level of confidence in them to be a factor in disclosure. For a scenario that could be considerable, a non-harmful error, 78.9% of respondents would not contact the family. Respondents with high disclosure scores were more likely to feel that disclosure was an opportunity for forgiveness (P=.003) and to have never seen major medical errors (P=.004). Conclusions: The surveyed radiation oncologists chose to respond with full disclosure at a high rate, although ideal disclosure practices were not uniformly adhered to beyond the initial decision to disclose the occurrence of the error.

All eyes on the patient: the influence of oncologists? nonverbal communication on breast cancer patients? trust

OpenAIRE

Hillen, Marij A.; de Haes, Hanneke C. J. M.; van Tienhoven, Geertjan; Bijker, Nina; van Laarhoven, Hanneke W. M.; Vermeulen, Dani?lle M.; Smets, Ellen M. A.

2015-01-01

Trust in the oncologist is crucial for breast cancer patients. It reduces worry, enhances decision making, and stimulates adherence. Optimal nonverbal communication by the oncologist, particularly eye contact, body posture, and smiling, presumably benefits patients? trust. We were the first to experimentally examine (1) how the oncologist?s nonverbal behavior influences trust, and (2) individual differences in breast cancer patients? trust. Analogue patients (APs) viewed one out of eight vers...

Seeking informed consent to Phase I cancer clinical trials: identifying oncologists' communication strategies.

Science.gov (United States)

Brown, Richard; Bylund, Carma L; Siminoff, Laura A; Slovin, Susan F

2011-04-01

Phase I clinical trials are the gateway to effective new cancer treatments. Many physicians have difficulty when discussing Phase I clinical trials. Research demonstrates evidence of suboptimal communication. Little is known about communication strategies used by oncologists when recruiting patients for Phase I trials. We analyzed audio recorded Phase I consultations to identify oncologists' communication strategies. Subjects were consecutive cancer patients from six medical oncologists attending one of three outpatient clinics at a major Cancer Center in the United States. Sixteen patients signed informed consent for audio recording of their consultations in which a Phase I study was discussed. These were transcribed in full and analyzed to identify communication strategies. Six communication themes emerged from the analysis: (1) orienting, (2) educating patients, (3) describing uncertainty and prognosis, (4) persuading, (5) decision making, and (6) making a treatment recommendation. As expected, although there was some common ground between communication in Phase I and the Phase II and III settings, there were distinct differences. Oncologists used persuasive communication, made explicit recommendations, or implicitly expressed a treatment preference and were choice limiting. This highlights the complexity of discussing Phase I trials and the need to develop strategies to aid oncologists and patients in these difficult conversations. Patient centered communication that values patient preferences while preserving the oncologist's agenda can be a helpful approach to these discussions. Copyright © 2010 John Wiley & Sons, Ltd.

Differences in oncologist communication across age groups and contributions to adjuvant decision outcomes.

Science.gov (United States)

Step, Mary M; Siminoff, Laura A; Rose, Julia H

2009-11-01

The objective of this study was to assess potential age-related differences in oncologist communication during conversations about adjuvant therapy decisions and subsequent patient decision outcomes. Communication was observed between a cross-section of female patients aged 40 to 80 with early-stage breast cancer (n=180) and their oncologists (n=36) in 14 academic and community oncology practices in two states. Sources of data included audio recordings of visits, followed by post-visit patient interviews. Communication during the visit was assessed using the Siminoff Communication Content and Affect Program. Patient outcome measures included self-reported satisfaction with decision, decision conflict, and decision regret. Results showed that oncologists were significantly more fluent and more direct with older than middle-aged patients and trended toward expressing their own treatment preferences more with older patients. Satisfaction with treatment decisions was highest for women in their 50s and 60s. Decision conflict was significantly associated with more discussion of oncologist treatment preferences and prognosis. Decision regret was significantly associated with patient age and education. Older adults considering adjuvant therapy may find that oncologists' communication accommodations to perceived deficiencies in older adult cognition or communication challenge their decision-making involvement. Oncologists should carefully assess patient decision-making preferences and be mindful of accommodating their speech to age-related stereotypes.

Characteristics of attitude and recommendation of oncologists toward exercise in South Korea: a cross sectional survey study.

Science.gov (United States)

Park, Ji-Hye; Oh, Minsuk; Yoon, Yong Jin; Lee, Chul Won; Jones, Lee W; Kim, Seung Il; Kim, Nam Kyu; Jeon, Justin Y

2015-04-10

The purpose of the present study was to examine 1) characteristics and attitudes of oncologists toward exercise and toward recommending exercise to their patients, 2) association among oncologists' own physical activity levels, exercise recommendations, and their attitudes toward recommending exercise. A total of 167 oncologists participated in this survey study (41 surgeons, 78 medical oncologists, 25 radiation oncologists, and 21 others). Most oncologists included in the study treat more than one type of cancer, including colorectal, gastric, breast, lung, and liver cancer. To analyze the data, the one-way ANOVA, and t-test were used. All data were indicated for mean, SD, and proportions. Most oncologists agreed that exercise is beneficial (72.8%) and important (69.6%), but only 39.2% of them agreed that exercise is safe, and only 7.2% believed that cancer patients manage to exercise during cancer treatment. Forty-six percentage of the surveyed oncologists recommended exercise to their patients during the past month. The average amount of participation in physical activity by oncologists who participated in the study was 139.5 ± 120.3 min per week, and 11.4% of the study participants met the American College of Sports Medicine (ACSM) guidelines. Oncologists' own physical activity levels were associated with their attitudes toward recommending exercise. Belief in the benefits of exercise in the performance of daily tasks, improvement of mental health, and the attenuation of physical decline from treatment were the three most prevalent reasons why oncologists recommend exercise to their patients. Barriers to recommending exercise to patients included lack of time, unclear exercise recommendations, and the safety of patients. Oncologists have favorable attitudes toward exercise and toward recommending exercise to their patients during treatment. However, they also experience barriers to recommending exercise, including lack of time, unclear exercise guidelines

Knowledge, attitudes and awareness regarding fertility preservation among oncologists and clinical practitioners in Lebanon.

Science.gov (United States)

Ghazeeri, Ghina; Zebian, Dina; Nassar, Anwar H; Harajly, Sally; Abdallah, Alain; Hakimian, Stephanie; Skaiff, Bassem; Abbas, Hussein A; Awwad, Johnny

2016-06-01

Fertility preservation (FP) aims to help individuals overcome the infertility associated with cancer treatments such as chemotherapy and radiation. The objective of this study was to assess the awareness, attitudes and knowledge of oncologists' and clinical practitioners' (CPs) about fertility preservation and its options in Lebanon. This was a cross-sectional study with surveys carried out between March 2012 and February 2013 on CPs at the American University of Beirut Medical Centre and Saint Jude's Children Cancer Centre as well as all registered oncologists in Lebanon. Ninety percent of CPs (n = 88) and 94% of oncologists (n = 53) agreed that fertility preservation should be discussed with patient before their cancer treatment. Our data showed a gender bias in relation to patients being informed of their FP options, as well as conflicting knowledge of FP options available in Lebanon among oncologists. The CPs were more likely to have accurate knowledge of FP options and treatment than oncologists. A proactive approach is required to: (1) increase the awareness and knowledge of FP; (2) improve attitudes towards FP; and (3) encourage its communication between CPs, oncologists and patients in Lebanon. Increased education programs, awareness campaigns and development of dedicated FP centres are needed.

Discrepant Views of Oncologists and Cancer Patients on Complementary and Alternative Medicine in a Chinese General Hospital.

Science.gov (United States)

Yang, Geliang; Zhang, Huiqing; Gan, Zheng; Fan, Yifu; Gu, Wei; Ling, Changquan

2018-06-01

Complementary and alternative medicine (CAM) has been widely used by cancer patients but rarely discussed by oncologists. This study was designed to evaluate the communication gap between China's oncologists and cancer patients on CAM. Two parallel cross-sectional studies assessed 83 oncologists and 402 cancer patients on CAM communication between patients and oncologists, and attitudes toward CAM use and clinical decisions about CAM. A majority (75.1%) of the cancer patients (302/402) were identified as CAM users within the most recent three months while 77.6% of the cancer patients (312/402) were identified as CAM users since diagnosis of cancer. Oncologists and patients responded differently ( P effectiveness of CAM, cancer patients were more likely to believe that CAM was effective while oncologists had more concerns about adverse effects of CAM use. CAM use by patients was predicted by disease duration (≥9 months) in the multivariable logistic regression model. China's oncologists and cancer patients may hold discrepant views on CAM. China's oncologists are encouraged to improve their knowledge on CAM and to initiate more discussions with their patients regarding effective and the safe use of CAM.

How attachment style and locus of control influence patients' trust in their oncologist

NARCIS (Netherlands)

Hillen, Marij A.; de Haes, Hanneke C. J. M.; Stalpers, Lukas J. A.; Klinkenbijl, Jean H. G.; Eddes, Eric-Hans; Verdam, Mathilde G. E.; Smets, Ellen M. A.

2014-01-01

Cancer patients need to trust their oncologist. How the oncologist communicates probably contributes to patients' trust. Yet, patient characteristics such as their attachment style and health locus of control may influence how such communication is perceived. We examined how these personality

How attachment style and locus of control influence patients' trust in their oncologist

NARCIS (Netherlands)

Hillen, M.A.; de Haes, H.C.J.M.; Stalpers, L.J.A.; Klinkenbijl, J.H.G.; Eddes, E.-H.; Verdam, M.G.E.; Smets, E.M.A.

2014-01-01

Objective: Cancer patients need to trust their oncologist. How the oncologist communicates probably contributes to patients' trust. Yet, patient characteristics such as their attachment style and health locus of control may influence how such communication is perceived. We examined how these

The well-being and personal wellness promotion strategies of medical oncologists in the North Central Cancer Treatment Group.

Science.gov (United States)

Shanafelt, Tait D; Novotny, Paul; Johnson, Mary E; Zhao, Xinghua; Steensma, David P; Lacy, Martha Q; Rubin, Joseph; Sloan, Jeff

2005-01-01

The well-being of oncologists is important to the well-being of their patients. While much is known about oncologist distress, little is known about oncologist well-being. We set out to evaluate oncologist well-being and the personal wellness promotion strategies used by oncologists. We performed a cross-sectional survey of medical oncologists in the North Central Cancer Treatment Group using a validated instrument to measure quality of life. Study-specific questions explored stressors, wellness promotion strategies and career satisfaction. Of 241 responding oncologists (response rate 61%), 121 (50%) reported high overall well-being. Being age 50 or younger (57 vs. 41%; p = 0.01), male (53 vs. 31%; p = 0.01) and working 60 h or less per week (50 vs. 33%; p = 0.005) were associated with increased overall well-being on bivariate analysis. Ratings of the importance of a number of personal wellness promotion strategies differed for oncologists with high well-being compared with those without high well-being. Developing an approach/philosophy to dealing with death and end-of-life care, using recreation/hobbies/exercise, taking a positive outlook and incorporating a philosophy of balance between personal and professional life were all rated as substantially more important wellness strategies by oncologists with high well-being (p values career satisfaction. Half of medical oncologists experience high overall well-being. Use of specific personal wellness promotion strategies appears to be associated with oncologist well-being. Further investigations of the prevalence, promotion, causes, inequities and clinical impact of physician well-being are needed. .

Grief symptoms and difficult patient loss for oncologists in response to patient death.

Science.gov (United States)

Granek, Leeat; Ben-David, Merav; Shapira, Shahar; Bar-Sela, Gil; Ariad, Samuel

2017-07-01

The study aimed to explore oncologist's grief symptoms over patient death and to identify why and which losses are particularly challenging when patients die. The grounded theory method was used to collect and analyze the data. Twenty-two oncologists were interviewed between March 2013 and June 2014 from three adult oncology centers in the north, center, and south of Israel. Oncologists were at different stages of their careers and varied in their sub-specialties, gender, and personal and professional backgrounds. Grief begun when the patient died, in anticipation of the patient's death, many days after the death, or when the patient received a poor prognosis. The phenomenological experience of grief for oncologists included behavioral, cognitive, physical, and emotional symptoms in response to patient death. Behavioral symptoms included crying and difficulties sleeping. Cognitive symptoms included self-doubt and rumination about the patient and the care the patient had received before death. Physical symptoms included chest pain, fatigue, and general physical discomfort. Emotional symptoms included sadness, anxiety, helplessness, guilt, relief, irritability, and loss. Difficult patient loss was caused by patient-related factors, family-related factors, and disease-related factors. Patient deaths result in behavioral, cognitive, physical, and emotional symptoms of grief in oncologists. These symptoms become particularly intense in the context of patient, family, and disease-related factors. Educational and supportive interventions for managing grief related to patient death are needed in order to support oncologists in their emotionally and mentally taxing work. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

ROS-IGTL-Bridge: an open network interface for image-guided therapy using the ROS environment.

Science.gov (United States)

Frank, Tobias; Krieger, Axel; Leonard, Simon; Patel, Niravkumar A; Tokuda, Junichi

2017-08-01

With the growing interest in advanced image-guidance for surgical robot systems, rapid integration and testing of robotic devices and medical image computing software are becoming essential in the research and development. Maximizing the use of existing engineering resources built on widely accepted platforms in different fields, such as robot operating system (ROS) in robotics and 3D Slicer in medical image computing could simplify these tasks. We propose a new open network bridge interface integrated in ROS to ensure seamless cross-platform data sharing. A ROS node named ROS-IGTL-Bridge was implemented. It establishes a TCP/IP network connection between the ROS environment and external medical image computing software using the OpenIGTLink protocol. The node exports ROS messages to the external software over the network and vice versa simultaneously, allowing seamless and transparent data sharing between the ROS-based devices and the medical image computing platforms. Performance tests demonstrated that the bridge could stream transforms, strings, points, and images at 30 fps in both directions successfully. The data transfer latency was bridge could achieve 900 fps for transforms. Additionally, the bridge was demonstrated in two representative systems: a mock image-guided surgical robot setup consisting of 3D slicer, and Lego Mindstorms with ROS as a prototyping and educational platform for IGT research; and the smart tissue autonomous robot surgical setup with 3D Slicer. The study demonstrated that the bridge enabled cross-platform data sharing between ROS and medical image computing software. This will allow rapid and seamless integration of advanced image-based planning/navigation offered by the medical image computing software such as 3D Slicer into ROS-based surgical robot systems.

All eyes on the patient: the influence of oncologists' nonverbal communication on breast cancer patients' trust.

Science.gov (United States)

Hillen, Marij A; de Haes, Hanneke C J M; van Tienhoven, Geertjan; Bijker, Nina; van Laarhoven, Hanneke W M; Vermeulen, Daniëlle M; Smets, Ellen M A

2015-08-01

Trust in the oncologist is crucial for breast cancer patients. It reduces worry, enhances decision making, and stimulates adherence. Optimal nonverbal communication by the oncologist, particularly eye contact, body posture, and smiling, presumably benefits patients' trust. We were the first to experimentally examine (1) how the oncologist's nonverbal behavior influences trust, and (2) individual differences in breast cancer patients' trust. Analogue patients (APs) viewed one out of eight versions of a video vignette displaying a consultation about chemotherapy treatment. All eight versions varied only in the oncologist's amount of eye contact (consistent vs. inconsistent), body posture (forward leaning vs. varying), and smiling (occasional smiling vs. no smiling). Primary outcome was trust in the observed oncologist (Trust in Oncologist Scale). 214 APs participated. Consistent eye contact led to stronger trust (β = -.13, p = .04). This effect was largely explained by lower educated patients, for whom the effect of consistent eye contact was stronger than for higher educated patients (β = .18, p = .01). A forward leaning body posture did not influence trust, nor did smiling. However, if the oncologist smiled more, he was perceived as more friendly (rs = .31, p < .001) and caring (rs = .18, p = .01). Older (β = .17, p = .01) and lower educated APs (β = -.25, p < .001) were more trusting. Trust was weaker for more avoidantly attached APs (β = -.16, p = .03). We experimentally demonstrated the importance of maintaining consistent eye contact for breast cancer patients' trust, especially among lower educated patients. These findings need to be translated into training for oncologists in how to optimize their nonverbal communication with breast cancer patients while simultaneously managing increased time pressure and computer use during the consultation.

American Society of Clinical Oncology Policy Statement: The Role of the Oncologist in Cancer Prevention and Risk Assessment

Science.gov (United States)

Zon, Robin T.; Goss, Elizabeth; Vogel, Victor G.; Chlebowski, Rowan T.; Jatoi, Ismail; Robson, Mark E.; Wollins, Dana S.; Garber, Judy E.; Brown, Powel; Kramer, Barnett S.

2009-01-01

Oncologists have a critical opportunity to utilize risk assessment and cancer prevention strategies to interrupt the initiation or progression of cancer in cancer survivors and individuals at high risk of developing cancer. Expanding knowledge about the natural history and prognosis of cancers positions oncologists to advise patients regarding the risk of second malignancies and treatment-related cancers. In addition, as recognized experts in the full spectrum of cancer care, oncologists are afforded opportunities for involvement in community-based cancer prevention activities. Although oncologists are currently providing many cancer prevention and risk assessment services to their patients, economic barriers exist, including inadequate or lack of insurance, that may compromise uniform patient access to these services. Additionally, insufficient reimbursement for existing and developing interventions may discourage patient access to these services. The American Society of Clinical Oncology (ASCO), the medical society representing cancer specialists involved in patient care and clinical research, is committed to supporting oncologists in their wide-ranging involvement in cancer prevention. This statement on risk assessment and prevention counseling, although not intended to be a comprehensive overview of cancer prevention describes the current role of oncologists in risk assessment and prevention; provides examples of risk assessment and prevention activities that should be offered by oncologists; identifies potential opportunities for coordination between oncologists and primary care physicians in prevention education and coordination of care for cancer survivors; describes ASCO's involvement in education and training of oncologists regarding prevention; and proposes improvement in the payment environment to encourage patient access to these services. PMID:19075281

Nuclear disasters: current plans and future directions for oncologists.

Science.gov (United States)

Goffman, Thomas E

2008-01-01

To show that there is a significant role for oncologists in the event of a terrorist nuclear disaster. Professionals need data on current political issues regarding a nuclear attack already put in place by the administration and the military. Review of what actually occurs during a fission bomb's explosion helps to point out what medical care will be most needed. The author contends that those trained in the oncologies could play a major part. Modern-day America. Potential civilian survivors. Large gaps noted in statewide disaster plans in the public domain. Oncologists must get involved now in disaster planning; statewide plans are necessary throughout the nation; the public needs to know the basics of what to do in the advent of a nuclear bomb explosion.

Oncologists' perspectives on post-cancer treatment communication and care coordination with primary care physicians.

Science.gov (United States)

Klabunde, C N; Haggstrom, D; Kahn, K L; Gray, S W; Kim, B; Liu, B; Eisenstein, J; Keating, N L

2017-07-01

Post-treatment cancer care is often fragmented and of suboptimal quality. We explored factors that may affect cancer survivors' post-treatment care coordination, including oncologists' use of electronic technologies such as e-mail and integrated electronic health records (EHRs) to communicate with primary care physicians (PCPs). We used data from a survey (357 respondents; participation rate 52.9%) conducted in 2012-2013 among medical oncologists caring for patients in a large US study of cancer care delivery and outcomes. Oncologists reported their frequency and mode of communication with PCPs, and role in providing post-treatment care. Seventy-five per cent said that they directly communicated with PCPs about post-treatment status and care recommendations for all/most patients. Among those directly communicating with PCPs, 70% always/usually used written correspondence, while 36% always/usually used integrated EHRs; telephone and e-mail were less used. Eighty per cent reported co-managing with PCPs at least one post-treatment general medical care need. In multivariate-adjusted analyses, neither communication mode nor intensity were associated with co-managing survivors' care. Oncologists' reliance on written correspondence to communicate with PCPs may be a barrier to care coordination. We discuss new research directions for enhancing communication and care coordination between oncologists and PCPs, and to better meet the needs of cancer survivors post-treatment. © 2017 John Wiley & Sons Ltd.

Satisfaction with work-life balance among U.S. gynecologic oncologists, a cross-sectional study

Science.gov (United States)

Szender, J Brian; Grzankowski, Kassondra S; Eng, Kevin H; Lele, Shashikant B; Odunsi, Kunle; Frederick, Peter J

2016-01-01

Objectives To evaluate the satisfaction with work-life balance (WLB) and career satisfaction of gynecologic oncologists. Methods In August 2014, members of the Society of Gynecologic Oncology (SGO) were sent an anonymous, cross-sectional survey evaluating demographic variables, practice characteristics, career satisfaction, fatigue, and satisfaction with WLB. Fatigue was assessed using a visual-analog scale. Career satisfaction and WLB were assessed with a Likert scale. Inferential statistics were computed with type I error rates of 0.05. Results Out of the 1002 gynecologic oncologists surveyed, 290 (28.9%) responded. Only 18.6% of respondents were satisfied with WLB and there were significant associations between gender (P = 0.0157), time spent in work related activities at home (P = 0.0024), on weekends (P = 0.0017), and in the hospital (P = 0.0001). More than 84% of physicians reported they would choose medicine as a career again and of those 90% would choose to be a gynecologic oncologist again. Fatigue was strongly associated with dissatisfaction with WLB in univariate and multivariate analysis (P < 0.0001). Conclusions Although gynecologic oncologists indicated they are satisfied with their careers, most are not satisfied with their WLB. Given the forecast shortage of gynecologic oncologists and projected increased cancer rates, understanding the factors associated with career satisfaction may assist the SGO in meeting future gynecologic cancer care needs. PMID:27088113

Biosimilars 101: considerations for U.S. oncologists in clinical practice

International Nuclear Information System (INIS)

Camacho, Luis H; Frost, Craig P; Abella, Esteban; Morrow, Phuong K; Whittaker, Sadie

2014-01-01

Biosimilars of biologics used for cancer treatment and supportive care are expected to enter the U.S. market soon. Biosimilars will be highly similar to their reference products, but unlike generic drugs, not identical. Differences between a biosimilar and its reference product may arise because of the complexity of biologics, and differences in the cell lines and processes used during manufacturing. Biosimilars will be approved in the United States through a regulatory pathway based on comparative analytical and clinical studies for their characterization and demonstration of no clinically meaningful differences from their reference products. Unlike generics, initial approval may not include interchangeability, as additional evidence may be required before a biosimilar could be approved as interchangeable with its reference product; interchangeable designation could allow pharmacy-level substitution without prescriber intervention. In some cases, the U.S. Food and Drug Administration (FDA) may extrapolate an indication that has not been formally investigated for the biosimilar but that is approved for the reference product. Robust safety monitoring of all biologics is important to track and accurately attribute adverse events, particularly because their inherent complexity and manufacturing differences make them susceptible to structural changes that can affect safety (e.g., immunogenicity). Accuracy of postapproval safety reports will partly depend on the biosimilar naming approach. Potential cost savings should be evaluated in the context of differences in manufacturers' patient-assistance programs, copayments, and institutional costs. A manufacturer's ability to ensure reliable supply of high-quality biosimilars should also be considered. Broad understanding of these issues is critical for oncologists preparing for their use in clinical practice

Pushing up daisies: implicit and explicit language in oncologist-patient communication about death.

Science.gov (United States)

Rodriguez, Keri L; Gambino, Frank J; Butow, Phyllis; Hagerty, Rebecca; Arnold, Robert M

2007-02-01

Although there are guidelines regarding how conversations with patients about prognosis in life-limiting illness should occur, there are little data about what doctors actually say. This study was designed to qualitatively analyze the language that oncologists and cancer patients use when talking about death. We recruited 29 adults who had incurable forms of cancer, were scheduled for a first-time visit with one of six oncologists affiliated with a teaching hospital in Australia, and consented to having their visit audiotaped and transcribed. Using content analytic techniques, we coded various features of language usage. Of the 29 visits, 23 (79.3%) included prognostic utterances about treatment-related and disease-related outcomes. In 12 (52.2%) of these 23 visits, explicit language about death ("terminal," variations of "death") was used. It was most commonly used by the oncologist after the physical examination, but it was sometimes used by patients or their kin, usually before the examination and involving emotional questioning about the patient's future. In all 23 (100%) visits, implicit language (euphemistic or indirect talk) was used in discussing death and focused on an anticipated life span (mentioned in 87.0% of visits), estimated time frame (69.6%), or projected survival (47.8%). Instead of using the word "death," most participants used some alternative phrase, including implicit language. Although oncologists are more likely than patients and their kin to use explicit language in discussing death, the oncologists tend to couple it with implicit language, possibly to mitigate the message effects.

Rosácea fulminante: relato de caso

Directory of Open Access Journals (Sweden)

José Otávio Alquezar Gozzano

2016-10-01

Full Text Available Introdução: Rosácea fulminante (RF ou pioderma facial é uma doença rara, descrita em 1940 por Kierland e O’Leary. É considerada uma variante extrema de rosácea conglobata, esta, consiste em formação de placas e abscessos hemorrágicos na pele. A RF tem sua etiologia desconhecida, porém há teorias que relacionam seu acometimento com a variação de hormônios femininos e a ingestão de vitamina B12. A RF é frequente em mulheres, principalmente pós- adolescentes. Apresenta-se abruptamente na face, amiúde na região mento- mandibular, através de pápulas inflamatórias, pústulas, cistos e nódulos com comedões escassos ou inexistentes, além de abcessos, sem manifestações sistêmicas e com a recidiva rara. Seu diagnóstico é fundamentalmente clínico, apenas com a história do paciente, sem necessidade de exames complementares. Para o tratamento, são utilizados corticoides orais, isotretinoína oral e antibióticos a fim de minimizar as sequelas físicas e psicológicas. Objetivo: Relatar caso de paciente com diagnóstico de rosácea fulminante. Metodologia: Paciente diagnosticada com rosácea fulminante atendida em serviço ambulatorial e revisão de literatura. Relato de caso: Paciente do sexo feminino, 19 anos, refere lesões súbitas em face há uma semana. Nega quadro acneico anterior, histórias de alergias e outras comorbidades. Relata ausência de uso de anticoncepcionais orais há 5 meses e data de última menstruação há 3 semanas, sem atraso menstrual. Ao exame: pápulas eritematosas e pústulas, além de pequenos nódulos inflamatórios na face. Hipótese diagnóstica: RF. Como conduta, foi prescrito tetraciclina. Conclusões: A RF é uma forma infrequente de rosácea, sendo importante o diagnóstico precoce e tratamento eficaz, a fim de melhorar a qualidade de vida do paciente.

ROS (Robot Operating System) für Automotive

OpenAIRE

Bubeck, Alexander

2014-01-01

- Introduction into the Robot Operating System - Open Source in the automotive industries - Application of ROS in the automotive industry - ROS navigation - ROS with real time control - ROS in the embedded world - Outlook: ROS 2.0 - Summary

ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis.

Science.gov (United States)

Kim, Young-Mee; Kim, Seok-Jo; Tatsunami, Ryosuke; Yamamura, Hisao; Fukai, Tohru; Ushio-Fukai, Masuko

2017-06-01

Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) and mitochondria play a critical role in growth factor-induced switch from a quiescent to an angiogenic phenotype in endothelial cells (ECs). However, how highly diffusible ROS produced from different sources can coordinate to stimulate VEGF signaling and drive the angiogenic process remains unknown. Using the cytosol- and mitochondria-targeted redox-sensitive RoGFP biosensors with real-time imaging, here we show that VEGF stimulation in human ECs rapidly increases cytosolic RoGFP oxidation within 1 min, followed by mitochondrial RoGFP oxidation within 5 min, which continues at least for 60 min. Silencing of Nox4 or Nox2 or overexpression of mitochondria-targeted catalase significantly inhibits VEGF-induced tyrosine phosphorylation of VEGF receptor type 2 (VEGFR2-pY), EC migration and proliferation at the similar extent. Exogenous hydrogen peroxide (H 2 O 2 ) or overexpression of Nox4, which produces H 2 O 2 , increases mitochondrial ROS (mtROS), which is prevented by Nox2 siRNA, suggesting that Nox2 senses Nox4-derived H 2 O 2 to promote mtROS production. Mechanistically, H 2 O 2 increases S36 phosphorylation of p66Shc, a key mtROS regulator, which is inhibited by siNox2, but not by siNox4. Moreover, Nox2 or Nox4 knockdown or overexpression of S36 phosphorylation-defective mutant p66Shc(S36A) inhibits VEGF-induced mtROS, VEGFR2-pY, EC migration, and proliferation. In summary, Nox4-derived H 2 O 2 in part activates Nox2 to increase mtROS via pSer36-p66Shc, thereby enhancing VEGFR2 signaling and angiogenesis in ECs. This may represent a novel feed-forward mechanism of ROS-induced ROS release orchestrated by the Nox4/Nox2/pSer36-p66Shc/mtROS axis, which drives sustained activation of angiogenesis signaling program. Copyright © 2017 the American Physiological Society.

All eyes on the patient: the influence of oncologists' nonverbal communication on breast cancer patients' trust

NARCIS (Netherlands)

Hillen, Marij A.; de Haes, Hanneke C. J. M.; van Tienhoven, Geertjan; Bijker, Nina; van Laarhoven, Hanneke W. M.; Vermeulen, Daniëlle M.; Smets, Ellen M. A.

2015-01-01

Trust in the oncologist is crucial for breast cancer patients. It reduces worry, enhances decision making, and stimulates adherence. Optimal nonverbal communication by the oncologist, particularly eye contact, body posture, and smiling, presumably benefits patients' trust. We were the first to

ROS Installation and Commissioning

CERN Multimedia

Gorini, B

The ATLAS Readout group (a sub-group of TDAQ) has now completed the installation and commissioning of all of the Readout System (ROS) units. Event data from ATLAS is initially handled by detector specific hardware and software, but following a Level 1 Accept the data passes from the detector specific Readout Drivers (RODs) to the ROS, the first stage of the central ATLAS DAQ. Within the final ATLAS TDAQ system the ROS stores the data and on request makes it available to the Level 2 Trigger (L2) processors and to the Event Builder (EB) as required. The ROS is implemented as a large number of PCs housing custom built cards (ROBINs) and running custom multi-threaded software. Each ROBIN card (shown below) contains buffer memories to store the data, plus a field programmable gate array ( FPGA ) and an embedded PowerPC processor for management of the memories and data requests, and is implemented as a 64-bit 66 MHz PCI card. Both the software and the ROBIN cards have been designed and developed by the Readout g...

Quantitative evaluation of radiation oncologists' adaptability to lower reimbursing treatment programs.

Science.gov (United States)

Gill, Beant S; Beriwal, Sushil; Rajagopalan, Malolan S; Wang, Hong; Hodges, Kimberly; Greenberger, Joel S

2015-01-01

Rapid development of sophisticated modalities has challenged radiation oncologists to evaluate workflow and care delivery processes. Our study assesses treatment modality use and willingness to alter management with anticipated limitations in reimbursement and resources. A web-based survey was sent to 43 radiation oncologists in a National Cancer Institute-designated comprehensive cancer center network. The survey contained 7 clinical cases with various acceptable treatment options based on our institutional clinical pathways. Each case was presented in 3 modules with varying situations: (1) unlimited resources with current reimbursement, (2) restricted reimbursement (bundled payment), and (3) both restricted reimbursement and resources. Reimbursement rates were based on the 2013 Medicare fee schedule. Adoption of lower reimbursing options (LROs) was defined as the percentage of scenarios in which a respondent selected an LRO compared with baseline. Forty-three physicians completed the survey, 11 (26%) at academic and 32 (74%) at community facilities. When bundled payment was imposed (module 1 vs 2), an increase in willingness to adopt LROs was observed (median 11.1%). When physicians were limited to both bundled payment and resource restriction, adoption of LROs was more pronounced (module 1 vs 3; median 22.2%, P 25 years, P = .02). Radiation oncologists were more likely to choose lower reimbursing treatment options when both resource restriction and bundled payment were presented. Those with fewer years of clinical practice were less inclined to alter management, perhaps reflecting modern residency training. Future cost-utility analyses may help to better guide radiation oncologists in selection of LROs. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Co-authorship patterns and networks of Korean radiation oncologists

International Nuclear Information System (INIS)

Choi, Jin Hyun; Kang, Jin Oh; Park, Seo Hyun; Kim, Sang Ki

2011-01-01

This research aimed to analyze the patterns of co-authorship network among the Korean radiation oncologists and to identify attributing factors for the formation of networks. A total of 1,447 articles including contents of 'Radiation Oncology' and 'Therapeutic Radiology' were searched from the KoreaMed database. The co-authorship was assorted by the author's full name, affiliation and specialties. UCINET 6.0 was used to figure out the author's network centrality and the cluster analysis, and KeyPlayer 1.44 program was used to get a result of key player index. Sociogram was analyzed with the Netdraw 2.090. The statistical comparison was performed by a t-test and ANOVA using SPSS 16.0 with p-value < 0.05 as the significant value. The number of articles written by a radiation oncologist as the fi rst author was 1,025 out of 1,447. The pattern of coauthorship was classified into fi ve groups. For articles of which the fi rst author was a radiation oncologist, the number of single author articles (type-A) was 81; single-institution articles (type-B) was 687; and multiple-author articles (type-C) was 257. For the articles which radiation oncologists participated in as a co-author, the number of single-institution articles (type-D) was 280 while multiple-institution articles (type-E) were 142. There were 8,895 authors from 1,366 co-authored articles, thus the average number of authors per article was 6.51. It was 5.73 for type-B, 6.44 for type-C, 7.90 for type-D, and 7.67 for type-E (p 0.000) in the average number of authors per article. The number of authors for articles from the hospitals published more than 100 articles was 7.23 while form others was 5.94 (p = 0.005). Its number was 5.94 and 7.16 for the articles published before and after 2001 (p = 0.000). The articles written by a radiation oncologist as the fi rst author had 5.92 authors while others for 7.82 (p = 0.025). Its number was 5.57 and 7.71 for the Journal of the Korean Society for Therapeutic Radiology

ROS signalling - specificity is required

DEFF Research Database (Denmark)

Møller, Ian M; Sweetlove, Lee J

2010-01-01

Reactive oxygen species (ROS) production increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 might induce a general stress response, but it does not have...... the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g. in chloroplasts or mitochondria. Here we argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS messengers...... and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. Likewise, unmodified peptides deriving from the breakdown of redundant proteins could help coordinate organellar and nuclear gene expression...

Young adult cancer survivors' follow-up care expectations of oncologists and primary care physicians.

Science.gov (United States)

Hugh-Yeun, Kiara; Kumar, Divjot; Moghaddamjou, Ali; Ruan, Jenny Y; Cheung, Winson Y

2017-06-01

Young adult cancer survivors face unique challenges associated with their illness. While both oncologists and primary care physicians (PCPs) may be involved in the follow-up care of these cancer survivors, we hypothesized that there is a lack of clarity regarding each physician's roles and responsibilities. A self-administered survey was mailed to young adult cancer survivors in British Columbia, Canada, who were aged 20 to 39 years at the time of diagnosis and alive at 2 to 5 years following the diagnosis to capture their expectations of oncologists and PCPs in various important domains of cancer survivorship care. Multivariate logistic regression models that adjusted for confounders were constructed to examine for predictors of the different expectations. Of 722 young cancer survivors surveyed, 426 (59%) responded. Among them, the majority were White women with breast cancer. Oncologists were expected to follow the patient's most recent cancer and treatment-related side effects while PCPs were expected to manage ongoing and future cancer surveillance as well as general preventative care. Neither physician was perceived to be responsible for addressing the return to daily activities, reintegration to interpersonal relationships, or sexual function. Older survivors were significantly less likely to expect oncologists (p = 0.03) and PCPs (p = 0.01) to discuss family planning when compared to their younger counterparts. Those who were White were significantly more likely to expect PCPs to discuss comorbidities (p = 0.009) and preventative care (p = 0.001). Young adult cancer survivors have different expectations of oncologists and PCPs with respect to their follow-up care. Physicians need to better clarify their roles in order to further improve the survivorship phase of cancer care for young adults. Young adult cancer survivors have different expectations of their oncologists and PCPs. Clarification of the roles of each physician group during follow-up can

A mixed-methods examination of communication between oncologists and primary care providers among primary care physicians in underserved communities.

Science.gov (United States)

Shen, Megan Johnson; Binz-Scharf, Maria; D'Agostino, Tom; Blakeney, Natasha; Weiss, Elisa; Michaels, Margo; Patel, Shilpa; McKee, M Diane; Bylund, Carma L

2015-03-15

Research has demonstrated that communication and care coordination improve cancer patient outcomes. To improve communication and care coordination, it is important to understand primary care providers' (PCPs') perceptions of communication with oncologists as well as PCPs' communication needs. A mixed-methods approach was used in the present study. In the qualitative phase of the study, 18 PCPs practicing in underserved, minority communities were interviewed about their experiences communicating with oncologists. In the quantitative phase of the study, 128 PCPs completed an online survey about their preferences, experiences, and satisfaction with communication with oncologists. Results indicated a PCP-oncologist gap in communication occurred between diagnosis and treatment. PCPs wanted more communication with oncologists, updates on their patients' prognosis throughout treatment, and to be contacted via telephone or email and saw their role as crucial in providing supportive care for their patients. Although PCPs recognize that they play a critical, proactive role in supporting patients throughout the continuum of their cancer care experience, existing norms regarding postreferral engagement and oncologist-PCP communication often hinder activation of this role among PCPs. Expected standards regarding the method, frequency, and quality of postreferral communication should be jointly articulated and made accountable between PCPs and oncologists to help improve cancer patients' quality of care, particularly in minority communities. © 2014 American Cancer Society.

Global curriculum in research literacy for the surgical oncologist.

Science.gov (United States)

Are, C; Yanala, U; Malhotra, G; Hall, B; Smith, L; Cummings, C; Lecoq, C; Wyld, L; Audisio, R A; Berman, R S

2018-01-01

The ability to provide optimal care to cancer patients depends on awareness of current evidence-based practices emanating from research or involvement in research where circumstances permit. The significant global variations in cancer-related research activity and its correlation to cancer-specific outcomes may have an influence on the care provided to cancer patients and their outcomes. The aim of this project is to develop a global curriculum in research literacy for the surgical oncologist. The leadership of the Society of Surgical Oncology and European Society of Surgical Oncology convened a global curriculum committee to develop a global curriculum in research literacy for the Surgical Oncologist. A global curriculum in research literacy is developed to incorporate the required domains considered to be essential to interpret the published research or become involved in research activity where circumstances permit. The purpose of this curriculum is to promote research literacy for the surgical oncologist, wherever they are based. It does not mandate direct research participation which may not be feasible due to restrictions within the local health-care delivery environment, socio-economic priorities and the educational environment of the individual institution where they work. A global curriculum in research literacy is proposed which may promote research literacy or encourage involvement in research activity where circumstances permit. It is hoped that this will enhance cancer-related research activity, promote awareness of optimal evidence-based practices and improve outcomes for cancer patients globally. Copyright © 2017 Society of Surgical Oncology, European Society of Surgical Oncology. Published by Elsevier Ltd.. All rights reserved.

Medical oncology future plan of the Spanish Society of Medical Oncology: challenges and future needs of the Spanish oncologists.

Science.gov (United States)

Rivera, F; Andres, R; Felip, E; Garcia-Campelo, R; Lianes, P; Llombart, A; Piera, J M; Puente, J; Rodriguez, C A; Vera, R; Virizuela, J A; Martin, M; Garrido, P

2017-04-01

The SEOM Future Plan is aimed at identifying the main challenges, trends and needs of the medical oncology speciality over the next years, including potential oncologist workforce shortages, and proposing recommendations to overcome them. The estimations of the required medical oncologists workforce are based on an updated Medical Oncologist Register in Spain, Medical Oncology Departments activity data, dedication times and projected cancer incidence. Challenges, needs and future recommendations were drawn from an opinion survey and an advisory board. A shortage of 211 FTE medical oncologist specialists has been established. To maintain an optimal ratio of 158 new cases/FTE, medical oncology workforce should reach 1881 FTE by 2035. Main recommendations to face the growing demand and complexity of oncology services include a yearly growth of 2.5% of medical oncologist's workforce until 2035, and development and application of more accurate quality indicators for cancer care and health outcomes measure.

Experiences and Opinions Related to End-of-Life Discussion: From Oncologists' and Resident Physicians' Perspectives.

Science.gov (United States)

Koh, Su-Jin; Kim, Shinmi; Kim, JinShil; Keam, Bhumsuk; Heo, Dae Seog; Lee, Kyung Hee; Kim, Bong-Seog; Kim, Jee Hyun; Chang, Hye Jung; Baek, Sun Kyung

2018-04-01

The aims of this study were to explore how oncologists and resident physicians practice end-of-life (EOL) discussions and to solicit their opinions on EOL discussions as a means to improve the quality of EOL care. A survey questionnaire was developed to explore the experiences and opinions about EOL discussions among oncologists and residents. Descriptive statistics, the t test, and the chisquare test were performed for the analyses. A total of 147 oncologists and 229 residents participated in this study. The study respondents reported diverse definitions of "terminal state," and mostrespondents tried to disclose the patient's condition to the patient and/or family members. Both groups were involved in EOL care discussions, with a rather low satisfaction level (57.82/100). The best timing to initiate discussionwas consideredwhen metastasis or disease recurrence occurred orwhen withdrawal of chemotherapy was anticipated. Furthermore, the study respondents suggested that patients and their family members should be included in the EOL discussion. Medical, legal, and ethical knowledge and communication difficulties along with practical issues were revealed as barriers and facilitators for EOL discussion. This study explored various perspectives of oncologists and resident physicians for EOL discussion. Since the Life-Sustaining-Treatment Decision-Making Act will be implemented shortly in Korea, now is the time for oncologists and residents to prepare themselves by acquiring legal knowledge and communication skills. To achieve this, education, training, and clinical tools for healthcare professionals are required.

Targeting TRPM2 in ROS-Coupled Diseases

Directory of Open Access Journals (Sweden)

Shinichiro Yamamoto

2016-09-01

Full Text Available Under pathological conditions such as inflammation and ischemia-reperfusion injury large amounts of reactive oxygen species (ROS are generated which, in return, contribute to the development and exacerbation of disease. The second member of the transient receptor potential (TRP melastatin subfamily, TRPM2, is a Ca2+-permeable non-selective cation channel, activated by ROS in an ADP-ribose mediated fashion. In other words, TRPM2 functions as a transducer that converts oxidative stress into Ca2+ signaling. There is good evidence that TRPM2 plays an important role in ROS-coupled diseases. For example, in monocytes the influx of Ca2+ through TRPM2 activated by ROS contributes to the aggravation of inflammation via chemokine production. In this review, the focus is on TRPM2 as a molecular linker between ROS and Ca2+ signaling in ROS-coupled diseases.

Targeting TRPM2 in ROS-Coupled Diseases.

Science.gov (United States)

Yamamoto, Shinichiro; Shimizu, Shunichi

2016-09-07

Under pathological conditions such as inflammation and ischemia-reperfusion injury large amounts of reactive oxygen species (ROS) are generated which, in return, contribute to the development and exacerbation of disease. The second member of the transient receptor potential (TRP) melastatin subfamily, TRPM2, is a Ca(2+)-permeable non-selective cation channel, activated by ROS in an ADP-ribose mediated fashion. In other words, TRPM2 functions as a transducer that converts oxidative stress into Ca(2+) signaling. There is good evidence that TRPM2 plays an important role in ROS-coupled diseases. For example, in monocytes the influx of Ca(2+) through TRPM2 activated by ROS contributes to the aggravation of inflammation via chemokine production. In this review, the focus is on TRPM2 as a molecular linker between ROS and Ca(2+) signaling in ROS-coupled diseases.

The ROS Workshop

CERN Multimedia

Francis, D.

The first week of February saw the taking place of the ReadOut Subsystem (ROS) workshop. The ROS is the subsystem of the Trigger, DAQ & DCS project which receives and buffers data from the detector ReadOut Drivers (RODs). On request it then provides a subset of this buffered data, the so-called Regions of Interest (RoI), to the Level 2 trigger. Using the subsequent Level 2 trigger decision, the ROS either removes the buffered event data from its buffers or sends the full event data to the Event Filter for further processing. The workshop took place over a four-day period at a location in the Jura. The average daily attendance was twenty people, which mainly represented the five main ATLAS institutes currently engaged in this Trigger, DAQ & DCS activity. The aim of the workshop was to bring to an end the current prototyping activities in this area and launch the next, final, phase of prototyping. This new phase of prototyping will build on the successful activities of the previous phase and will focus...

Chaos theory: A fascinating concept for oncologists

International Nuclear Information System (INIS)

Denis, F.; Letellier, C.

2012-01-01

The oncologist is confronted daily by questions related to the fact that any patient presents a specific evolution for his cancer: he is challenged by very different, unexpected and often unpredictable outcomes, in some of his patients. The mathematical approach used today to describe this evolution has recourse to statistics and probability laws: such an approach does not ultimately apply to one particular patient, but to a given more or less heterogeneous population. This approach therefore poorly characterizes the dynamics of this disease and does not allow to state whether a patient is cured, to predict if he will relapse and when this could occur, and in what form, nor to predict the response to treatment and, in particular, to radiation therapy. Chaos theory, not well known by oncologists, could allow a better understanding of these issues. Developed to investigate complex systems producing behaviours that cannot be predicted due to a great sensitivity to initial conditions, chaos theory is rich of suitable concepts for a new approach of cancer dynamics. This article is three-fold: to provide a brief introduction to chaos theory, to clarify the main connecting points between chaos and carcinogenesis and to point out few promising research perspectives, especially in radiotherapy. (authors)

ROS-related redox regulation and signaling in plants.

Science.gov (United States)

Noctor, Graham; Reichheld, Jean-Philippe; Foyer, Christine H

2017-07-18

As sessile oxygenic organisms with a plastic developmental programme, plants are uniquely positioned to exploit reactive oxygen species (ROS) as powerful signals. Plants harbor numerous ROS-generating pathways, and these oxidants and related redox-active compounds have become tightly embedded into plant function and development during the course of evolution. One dominant view of ROS-removing systems sees them as beneficial antioxidants battling to keep damaging ROS below dangerous levels. However, it is now established that ROS are a necessary part of subcellular and intercellular communication in plants and that some of their signaling functions require ROS-metabolizing systems. For these reasons, it is suggested that "ROS processing systems" would be a more accurate term than "antioxidative systems" to describe cellular components that are most likely to interact with ROS and, in doing so, transmit oxidative signals. Within this framework, our update provides an overview of the complexity and compartmentation of ROS production and removal. We place particular emphasis on the importance of ROS-interacting systems such as the complex cellular thiol network in the redox regulation of phytohormone signaling pathways that are crucial for plant development and defense against external threats. Copyright © 2017 Elsevier Ltd. All rights reserved.

Awareness and behavior of oncologists and support measures in medical institutions related to ongoing employment of cancer patients in Japan.

Science.gov (United States)

Wada, Koji; Ohtsu, Mayumi; Aizawa, Yoshiharu; Tanaka, Hiroshi; Tagaya, Nobumi; Takahashi, Miyako

2012-04-01

Improved outcomes of cancer treatment allow patients to undergo treatment while working. However, support from oncologists and medical institutions is essential for patients to continue working. This study aimed to clarify oncologists' awareness and behavior regarding patients who work during treatment, support in medical institutions and their association. A questionnaire was mailed to all 453 diplomates and faculty of the subspecialty board of medical oncology in the Japanese Society of Medical Oncology and all 1016 surgeons certified by the Japanese Board of Cancer Therapy living in the Kanto area. The questionnaire assessed demographics, oncologist awareness and behavior regarding patient employment and support measures at their medical institutions. Logistic regression analysis was used to examine the association of awareness and behavior of oncologists with support measures at their institutions. A total of 668 individuals participated. The overall response rate was 45.5%. Only 53.6% of respondents advised patients to tell their supervisors about prospects for treatment and ask for understanding. For medical institutions, 28.8% had a nurse-involved counseling program and adjustments in radiation therapy (28.0%) and chemotherapy (41.9%) schedules to accommodate patients' work. There was a significant correlation between awareness and behavior of oncologists and medical institutions' measures to support employed cancer patients. There is room for improvement in awareness and behavior of oncologists and support in medical institutions for cancer patients continuing to work. Oncologists could support working patients by exerting influence on their medical institutions. Conversely, proactive development of support measures by medical institutions could alter the awareness and behavior of oncologists.

Awareness and behavior of oncologists and support measures in medical institutions related to ongoing employment of cancer patients in Japan

International Nuclear Information System (INIS)

Wada, Koji; Aizawa, Yoshiharu; Ohtsu, Mayumi; Tanaka, Hiroshi; Tagaya, Nobumi; Takahashi, Miyako

2012-01-01

Improved outcomes of cancer treatment allow patients to undergo treatment while working. However, support from oncologists and medical institutions is essential for patients to continue working. This study aimed to clarify oncologists' awareness and behavior regarding patients who work during treatment, support in medical institutions and their association. A questionnaire was mailed to all 453 diplomates and faculty of the subspecialty board of medical oncology in the Japanese Society of Medical Oncology and all 1016 surgeons certified by the Japanese Board of Cancer Therapy living in the Kanto area. The questionnaire assessed demographics, oncologist awareness and behavior regarding patient employment and support measures at their medical institutions. Logistic regression analysis was used to examine the association of awareness and behavior of oncologists with support measures at their institutions. A total of 668 individuals participated. The overall response rate was 45.5%. Only 53.6% of respondents advised patients to tell their supervisors about prospects for treatment and ask for understanding. For medical institutions, 28.8% had a nurse-involved counseling program and adjustments in radiation therapy (28.0%) and chemotherapy (41.9%) schedules to accommodate patients' work. There was a significant correlation between awareness and behavior of oncologists and medical institutions' measures to support employed cancer patients. There is room for improvement in awareness and behavior of oncologists and support in medical institutions for cancer patients continuing to work. Oncologists could support working patients by exerting influence on their medical institutions. Conversely, proactive development of support measures by medical institutions could alter the awareness and behavior of oncologists. (author)

Learning ROS for robotics programming

CERN Document Server

Martinez, Aaron

2013-01-01

The book will take an easy-to-follow and engaging tutorial approach, providing a practical and comprehensive way to learn ROS.If you are a robotic enthusiast who wants to learn how to build and program your own robots in an easy-to-develop, maintainable and shareable way, ""Learning ROS for Robotics Programming"" is for you. In order to make the most of the book, you should have some C++ programming background, knowledge of GNU/Linux systems, and computer science in general. No previous background on ROS is required, since this book provides all the skills required. It is also advisable to hav

A mixed methods analysis of experiences and expectations among early-career medical oncologists in Australia.

Science.gov (United States)

Wong, W K Tim; Kirby, Emma; Broom, Alex; Sibbritt, David; Francis, Kay; Karapetis, Christos S; Karikios, Deme; Harrup, Rosemary; Lwin, Zarnie

2018-01-26

A viable and sustainable medical oncology profession is integral for meeting the increasing demand for quality cancer care. The aim of this study was to explore the workforce-related experiences, perceptions and career expectations of early-career medical oncologists in Australia. A mixed-methods design, including a survey (n  =  170) and nested qualitative semistructured interviews (n  =  14) with early-career medical oncologists. Recruitment was through the Medical Oncology Group of Australia. Qualitative data were thematically analyzed and for the survey results, logistic regression modeling was conducted. Early-career medical oncologists experienced uncertainty regarding their future employment opportunities. The competitive job market has made them cautious about securing a preferred job leading to a perceived need to improve their qualifications through higher degree training and research activities. The following themes and trends were identified from the qualitative and quantitative analyses: age, career stage and associated early-career uncertainty; locale, professional competition and training preferences; participation in research and evolving professional expectations; and workload and career development opportunities as linked to career uncertainty. Perceived diminished employment opportunities in the medical oncology profession, and shifting expectations to be "more qualified," have increased uncertainty among junior medical oncologists in terms of their future career prospects. Structural factors relating to adequate funding of medical oncology positions may facilitate or inhibit progressive change in the workforce and its sustainability. Workforce planning and strategies informed by findings from this study will be necessary in ensuring that both the needs of cancer patients and of medical oncologists are met. © 2018 John Wiley & Sons Australia, Ltd.

Contemporary management of stage i testicular seminoma: a survey of Canadian radiation oncologists

Science.gov (United States)

Samant, R.; Alomary, I.; Genest, P.; Eapen, L.

2008-01-01

Recently published studies clearly indicate that there are now several acceptable options for managing stage i testicular seminoma patients after orchiectomy. We therefore decided to survey Canadian radiation oncologists to determine how they currently manage such patients and to compare the results with previous surveys. Our results demonstrate that adjuvant single-agent chemotherapy is being considered as an option by an increasing proportion of radiation oncologists (although it is not considered the preferred option), the routine use of radiotherapy is declining, and surveillance is becoming increasingly popular and is recommended most often. PMID:18769613

Stress, satisfaction and burnout amongst Australian and New Zealand radiation oncologists.

Science.gov (United States)

Leung, John; Rioseco, Pilar; Munro, Philip

2015-02-01

The aim of this study was to determine the self-reported prevalence of stress, job satisfaction and burnout among radiation oncologists in Australia and New Zealand. A secondary aim was to determine the association between stress and satisfaction parameters with burnout. An anonymous online survey was distributed to all radiation oncologists listed on Royal Australian and New Zealand College of Radiologists membership database. There were 37 Likert scale questions on stress, 17 Likert scale questions on job satisfaction and burnout assessed by the Maslach Burnout Inventory - Human Services Survey (MBI-HSS). A principal component analysis was done for stress and satisfaction to identify specific areas. Independent samples t-tests and analysis of variances were done. There were 220 responses out of 348 eligible respondents (63.2% response rate).For stress, a principal component analysis identified five areas: delivery demands, demands on time, continuing professional development (CPD), value and security, and interpersonal/teaching demands. Specialist radiation oncologists were more stressed by value and security than generalists (P stress associated with delivery demands, demands on time and CPD compared with others (P = 0.01). Those over 60 years were less stressed by delivery demands (P = 0.02), demands on time (P = 0.01) and CPD (P = 0.01) than their younger colleagues. Four satisfaction factors were identified in the principal component analysis: resources/remuneration, status/security, delivery of services and professional activities. [Correction added on 15 August 2014, after first online publication: stress/security was replaced with status/security.] Males and Australian radiation oncologists were more satisfied with professional activities (P = 0.02). Brachytherapy specialists were more satisfied with status/security (P = 0.01) while those interested in urology were more satisfied with resources/renumeration (P = 0.01) and

Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

Energy Technology Data Exchange (ETDEWEB)

Baldini, Elizabeth H., E-mail: ebaldini@partners.org [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Bosch, Walter [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Roberge, David [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Haas, Rick L.M. [Department of Radiotherapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Catton, Charles N. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Indelicato, Daniel J. [Department of Radiation Oncology, University of Florida Medical Center, Jacksonville, Florida (United States); Olsen, Jeffrey R. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States); Deville, Curtiland [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Chen, Yen-Lin [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Finkelstein, Steven E. [Translational Research Consortium, 21st Century Oncology, Scottsdale, Arizona (United States); DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Wang, Dian [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States)

2015-08-01

Purpose: The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials: Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions: For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed.

Retroperitoneal Sarcoma Target Volume and Organ at Risk Contour Delineation Agreement Among NRG Sarcoma Radiation Oncologists

International Nuclear Information System (INIS)

Baldini, Elizabeth H.; Abrams, Ross A.; Bosch, Walter; Roberge, David; Haas, Rick L.M.; Catton, Charles N.; Indelicato, Daniel J.; Olsen, Jeffrey R.; Deville, Curtiland; Chen, Yen-Lin; Finkelstein, Steven E.; DeLaney, Thomas F.; Wang, Dian

2015-01-01

Purpose: The purpose of this study was to evaluate the variability in target volume and organ at risk (OAR) contour delineation for retroperitoneal sarcoma (RPS) among 12 sarcoma radiation oncologists. Methods and Materials: Radiation planning computed tomography (CT) scans for 2 cases of RPS were distributed among 12 sarcoma radiation oncologists with instructions for contouring gross tumor volume (GTV), clinical target volume (CTV), high-risk CTV (HR CTV: area judged to be at high risk of resulting in positive margins after resection), and OARs: bowel bag, small bowel, colon, stomach, and duodenum. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: Ten radiation oncologists contoured both RPS cases, 1 contoured only RPS1, and 1 contoured only RPS2 such that each case was contoured by 11 radiation oncologists. The first case (RPS 1) was a patient with a de-differentiated (DD) liposarcoma (LPS) with a predominant well-differentiated (WD) component, and the second case (RPS 2) was a patient with DD LPS made up almost entirely of a DD component. Contouring agreement for GTV and CTV contours was high. However, the agreement for HR CTVs was only moderate. For OARs, agreement for stomach, bowel bag, small bowel, and colon was high, but agreement for duodenum (distorted by tumor in one of these cases) was fair to moderate. Conclusions: For preoperative treatment of RPS, sarcoma radiation oncologists contoured GTV, CTV, and most OARs with a high level of agreement. HR CTV contours were more variable. Further clarification of this volume with the help of sarcoma surgical oncologists is necessary to reach consensus. More attention to delineation of the duodenum is also needed

Patient-oncologist cost communication, financial distress, and medication adherence.

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Bestvina, Christine M; Zullig, Leah L; Rushing, Christel; Chino, Fumiko; Samsa, Gregory P; Altomare, Ivy; Tulsky, James; Ubel, Peter; Schrag, Deborah; Nicolla, Jon; Abernethy, Amy P; Peppercorn, Jeffrey; Zafar, S Yousuf

2014-05-01

Little is known about the association between patient-oncologist discussion of cancer treatment out-of-pocket (OOP) cost and medication adherence, a critical component of quality cancer care. We surveyed insured adults receiving anticancer therapy. Patients were asked if they had discussed OOP cost with their oncologist. Medication nonadherence was defined as skipping doses or taking less medication than prescribed to make prescriptions last longer, or not filling prescriptions because of cost. Multivariable analysis assessed the association between nonadherence and cost discussions. Among 300 respondents (86% response), 16% (n = 49) reported high or overwhelming financial distress. Nineteen percent (n = 56) reported talking to their oncologist about cost. Twenty-seven percent (n = 77) reported medication nonadherence. To make a prescription last longer, 14% (n = 42) skipped medication doses, and 11% (n = 33) took less medication than prescribed; 22% (n = 66) did not fill a prescription because of cost. Five percent (n = 14) reported chemotherapy nonadherence. To make a prescription last longer, 1% (n = 3) skipped chemotherapy doses, and 2% (n = 5) took less chemotherapy; 3% (n = 10) did not fill a chemotherapy prescription because of cost. In adjusted analyses, cost discussion (odds ratio [OR] = 2.58; 95% CI, 1.14 to 5.85; P = .02), financial distress (OR = 1.64, 95% CI, 1.38 to 1.96; P financial burden than expected (OR = 2.89; 95% CI, 1.41 to 5.89; P financial distress were associated with medication nonadherence, suggesting that cost discussions are important for patients forced to make cost-related behavior alterations. Future research should examine the timing, content, and quality of cost-discussions. Copyright © 2014 by American Society of Clinical Oncology.

Patient-oncologist alliance as protection against suicidal ideation in young adults with advanced cancer.

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Trevino, Kelly M; Abbott, Caroline H; Fisch, Michael J; Friedlander, Robert J; Duberstein, Paul R; Prigerson, Holly G

2014-08-01

Young adults with cancer are at an increased risk of suicidal ideation. To the authors' knowledge, the impact of the patient-oncologist alliance on suicidal ideation has not been examined to date. The current study examined the relationship between the patient-oncologist therapeutic alliance and suicidal ideation in young adults with advanced cancer. A total of 93 young adult patients (aged 20 years-40 years) with incurable, recurrent, or metastatic cancer were evaluated by trained interviewers. Suicidal ideation was assessed with the Yale Evaluation of Suicidality scale, dichotomized into a positive and negative score. Predictors included diagnoses of major depressive disorder and posttraumatic stress disorder, physical quality of life, social support, and use of mental health and supportive care services. The Human Connection Scale, dichotomized into a strong (upper third) and weak (lower two-thirds) therapeutic alliance, assessed the strength of the patients' perceived oncologist alliance. Approximately 22.6% of patients screened positive for suicidal ideation. Patients with a strong therapeutic alliance were found to be at reduced risk of suicidal ideation after controlling for confounding influences of cancer diagnosis, Karnofsky performance status, number of physical symptoms, physical quality of life, major depressive disorder, posttraumatic stress disorder, and social support. A strong therapeutic alliance was also associated with a reduced risk of suicidal ideation after controlling for mental health discussions with health care providers and use of mental health interventions. The patient-oncologist alliance was found to be a robust predictor of suicidal ideation and provided better protection against suicidal ideation than mental health interventions, including psychotropic medications. Oncologists may significantly influence patients' mental health and may benefit from training and guidance in building strong alliances with their young adult patients. �

Crizotinib-Resistant ROS1 Mutations Reveal a Predictive Kinase Inhibitor Sensitivity Model for ROS1- and ALK-Rearranged Lung Cancers.

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Facchinetti, Francesco; Loriot, Yohann; Kuo, Mei-Shiue; Mahjoubi, Linda; Lacroix, Ludovic; Planchard, David; Besse, Benjamin; Farace, Françoise; Auger, Nathalie; Remon, Jordi; Scoazec, Jean-Yves; André, Fabrice; Soria, Jean-Charles; Friboulet, Luc

2016-12-15

The identification of molecular mechanisms conferring resistance to tyrosine kinase inhibitor (TKI) is a key step to improve therapeutic results for patients with oncogene addiction. Several alterations leading to EGFR and anaplastic lymphoma kinase (ALK) resistance to TKI therapy have been described in non-small cell lung cancer (NSCLC). Only two mutations in the ROS1 kinase domain responsible for crizotinib resistance have been described in patients thus far. A patient suffering from a metastatic NSCLC harboring an ezrin (EZR)-ROS1 fusion gene developed acquired resistance to the ALK/ROS1 inhibitor crizotinib. Molecular analysis (whole-exome sequencing, CGH) and functional studies were undertaken to elucidate the mechanism of resistance. Based on this case, we took advantage of the structural homology of ROS1 and ALK to build a predictive model for drug sensitivity regarding future ROS1 mutations. Sequencing revealed a dual mutation, S1986Y and S1986F, in the ROS1 kinase domain. Functional in vitro studies demonstrated that ROS1 harboring either the S1986Y or the S1986F mutation, while conferring resistance to crizotinib and ceritinib, was inhibited by lorlatinib (PF-06463922). The patient's clinical response confirmed the potency of lorlatinib against S1986Y/F mutations. The ROS1 S1986Y/F and ALK C1156Y mutations are homologous and displayed similar sensitivity patterns to ALK/ROS1 TKIs. We extended this analogy to build a model predicting TKI efficacy against potential ROS1 mutations. Clinical evidence, in vitro validation, and homology-based prediction provide guidance for treatment decision making for patients with ROS1-rearranged NSCLC who progressed on crizotinib. Clin Cancer Res; 22(24); 5983-91. ©2016 AACR. ©2016 American Association for Cancer Research.

What advice are oncologists and surgeons in the United Kingdom giving to breast cancer patients about physical activity?

Directory of Open Access Journals (Sweden)

Daley Amanda J

2008-09-01

Full Text Available Abstract Evidence has shown that physical activity may attenuate the negative physical, psychological and functional effects of treatment in women diagnosed with breast cancer. Physical activity levels also decline substantially during and after completion of treatment for cancer, highlighting the importance of strategies to promote participation in regular physical activity in this population. Oncologists and surgeons may serve as an influential source of motivation to be physically activity in cancer patients, by conveying the importance of a healthy lifestyle. The primary purpose of the present study was to investigate whether oncologists and surgeons routinely discuss physical activity with their breast cancer patients and to investigate the nature of any information/advice provided during consultations. A secondary aim was to examine whether physically active oncologists and surgeons were more likely to provide advice about physical activity to patients, than inactive oncologists and surgeons. A brief postal questionnaire was sent to 710 consultant breast cancer oncologists and surgeons throughout the UK and 102 responded (response rate = 14.4%. Of responders, most (55.9% did not routinely discuss physical activity with their patients. Amongst oncologists/surgeons (clinicians who did offer advice, most focussed on discussing the benefits of physical activity for physical and functional health gains and for facilitating weight control and maintenance. A number of clinicians indicated they advised patients that physical activity may decrease risk of recurrence and improve survival, despite the lack of evidence from RCTs to support this suggestion. There was no significant association between the physical activity status of oncologists/surgeons and the likelihood that they discussed physical activity with patients. Educational strategies aimed at encouraging clinicians to promote physical activity in consultations need to be targeted widely

Attitudes Toward Family Involvement in Cancer Treatment Decision Making: The Perspectives of Patients, Family Caregivers, and Their Oncologists.

Science.gov (United States)

Shin, Dong Wook; Cho, Juhee; Roter, Debra L; Kim, So Young; Yang, Hyung Kook; Park, Keeho; Kim, Hyung Jin; Shin, Hee-Young; Kwon, Tae Gyun; Park, Jong Hyock

2017-06-01

To investigate how cancer patients, family caregiver, and their treating oncologist view the risks and benefits of family involvement in cancer treatment decision making (TDM) or the degree to which these perceptions may differ. A nationwide, multicenter survey was conducted with 134 oncologists and 725 of their patients and accompanying caregivers. Participant answered to modified Control Preferences Scale and investigator-developed questionnaire regarding family involvement in cancer TDM. Most participants (>90%) thought that family should be involved in cancer TDM. When asked if the oncologist should allow family involvement if the patient did not want them involved, most patients and caregivers (>85%) thought they should. However, under this circumstance, only 56.0% of oncologists supported family involvement. Patients were significantly more likely to skew their responses toward patient rather than family decisional control than were their caregivers (P family decisional control than caregivers (P family involvement is helpful and neither hamper patient autonomy nor complicate cancer TDM process. Oncologists were largely positive, but less so in these ratings than either patients or caregivers (P family caregivers, and, to a lesser degree, oncologists expect and valued family involvement in cancer TDM. These findings support a reconsideration of traditional models focused on protection of patient autonomy to a more contextualized form of relational autonomy, whereby the patient and family caregivers can be seen as a unit for autonomous decision. Copyright © 2016 John Wiley & Sons, Ltd.

The effect of artichoke (Cynara scolymus L.) extract on ROS generation in HUVEC cells.

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Juzyszyn, Z; Czerny, B; Pawlik, A; Droździk, M

2008-09-01

The effect of an artichoke extract on induced reactive oxygen species (ROS) generation in cultured human umbilical endothelial cells (HUVECs) and its reductive properties were evaluated. Preincubation of HUVEC cells with the artichoke extract at concentrations of 25-100 microg/mL for 24 h abolished ROS generation induced by LPS and oxyLDL as evaluated by the fluorescence intensity of 2',7'-dichlorofluorescein (DCF). Potent, concentration-dependent reductive properties of the artichoke extract were demonstrated by the reduction kinetics of cytochrome c in reference to ascorbate were also revealed. The results of the present study the warrant application of artichoke extracts as endothelium protecting agents.

Optimal ROS Signaling Is Critical for Nuclear Reprogramming

Directory of Open Access Journals (Sweden)

Gang Zhou

2016-05-01

Full Text Available Efficient nuclear reprogramming of somatic cells to pluripotency requires activation of innate immunity. Because innate immune activation triggers reactive oxygen species (ROS signaling, we sought to determine whether there was a role of ROS signaling in nuclear reprogramming. We examined ROS production during the reprogramming of doxycycline (dox-inducible mouse embryonic fibroblasts (MEFs carrying the Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc [OSKM] into induced pluripotent stem cells (iPSCs. ROS generation was substantially increased with the onset of reprogramming. Depletion of ROS via antioxidants or Nox inhibitors substantially decreased reprogramming efficiency. Similarly, both knockdown and knockout of p22phox—a critical subunit of the Nox (1–4 complex—decreased reprogramming efficiency. However, excessive ROS generation using genetic and pharmacological approaches also impaired reprogramming. Overall, our data indicate that ROS signaling is activated early with nuclear reprogramming, and optimal levels of ROS signaling are essential to induce pluripotency.

Oncologists' non-verbal behavior and analog patients' recall of information

NARCIS (Netherlands)

Hillen, Marij A.; de Haes, Hanneke C. J. M.; van Tienhoven, Geertjan; van Laarhoven, Hanneke W. M.; van Weert, Julia C. M.; Vermeulen, Daniëlle M.; Smets, Ellen M. A.

2016-01-01

Background Information in oncological consultations is often excessive. Those patients who better recall information are more satisfied, less anxious and more adherent. Optimal recall may be enhanced by the oncologist's non-verbal communication. We tested the influence of three non-verbal behaviors,

Digestive oncologist in the gastroenterology training curriculum

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Mulder, Chris Jacob Johan; Peeters, Marc; Cats, Annemieke; Dahele, Anna; Droste, Jochim Terhaar sive

2011-01-01

Until the late 1980s, gastroenterology (GE) was considered a subspecialty of Internal Medicine. Today, GE also incorporates Hepatology. However, Digestive Oncology training is poorly defined in the Hepatogastroenterology (HGE)-curriculum. Therefore, a Digestive Oncology curriculum should be developed and this document might be a starting point for such a curriculum. HGE-specialists are increasingly resisting the paradigm in which they play only a diagnostic and technical role in the management of digestive tumors. We suggest minimum end-points in the standard HGE-curriculum for oncology, and recommend a focus year in the Netherlands for Digestive Oncology in the HGE-curriculum. To produce well-trained digestive oncologists, an advanced Digestive Oncology training program with specific qualifications in Digestive Oncology (2 years) has been developed. The schedule in Belgium includes a period of at least 6 mo to be spent in a medical oncology department. The goal of these programs remains the production of well-trained digestive oncologists. HGE specialists are part of the multidisciplinary oncological teams, and some have been administering chemotherapy in their countries for years. In this article, we provide a road map for the organization of a proper training in Digestive Oncology. We hope that the World Gastroenterology Organisation and other (inter)national societies will support the necessary certifications for this specific training in the HGE-curriculum. PMID:21556128

[Chaos theory: a fascinating concept for oncologists].

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Denis, F; Letellier, C

2012-05-01

The oncologist is confronted daily by questions related to the fact that any patient presents a specific evolution for his cancer: he is challenged by very different, unexpected and often unpredictable outcomes, in some of his patients. The mathematical approach used today to describe this evolution has recourse to statistics and probability laws: such an approach does not ultimately apply to one particular patient, but to a given more or less heterogeneous population. This approach therefore poorly characterizes the dynamics of this disease and does not allow to state whether a patient is cured, to predict if he will relapse and when this could occur, and in what form, nor to predict the response to treatment and, in particular, to radiation therapy. Chaos theory, not well known by oncologists, could allow a better understanding of these issues. Developed to investigate complex systems producing behaviours that cannot be predicted due to a great sensitivity to initial conditions, chaos theory is rich of suitable concepts for a new approach of cancer dynamics. This article is three-fold: to provide a brief introduction to chaos theory, to clarify the main connecting points between chaos and carcinogenesis and to point out few promising research perspectives, especially in radiotherapy. Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

The role of mitochondrial ROS in the aging brain.

Science.gov (United States)

Stefanatos, Rhoda; Sanz, Alberto

2018-03-01

The brain is the most complex human organ, consuming more energy than any other tissue in proportion to its size. It relies heavily on mitochondria to produce energy and is made up of mitotic and postmitotic cells that need to closely coordinate their metabolism to maintain essential bodily functions. During aging, damaged mitochondria that produce less ATP and more reactive oxygen species (ROS) accumulate. The current consensus is that ROS cause oxidative stress, damaging mitochondria and resulting in an energetic crisis that triggers neurodegenerative diseases and accelerates aging. However, in model organisms, increasing mitochondrial ROS (mtROS) in the brain extends lifespan, suggesting that ROS may participate in signaling that protects the brain. Here, we summarize the mechanisms by which mtROS are produced at the molecular level, how different brain cells and regions produce different amounts of mtROS, and how mtROS levels change during aging. Finally, we critically discuss the possible roles of ROS in aging as signaling molecules and damaging agents, addressing whether age-associated increases in mtROS are a cause or a consequence of aging. © 2017 Federation of European Biochemical Societies.

Future Supply and Demand for Oncologists : Challenges to Assuring Access to Oncology Services

Science.gov (United States)

Erikson, Clese; Salsberg, Edward; Forte, Gaetano; Bruinooge, Suanna; Goldstein, Michael

2007-01-01

Purpose To conduct a comprehensive analysis of supply of and demand for oncology services through 2020. This study was commissioned by the Board of Directors of ASCO. Methods New data on physician supply gathered from surveys of practicing oncologists, oncology fellows, and fellowship program directors were analyzed, along with 2005 American Medical Association Masterfile data on practicing medical oncologists, hematologists/oncologists, and gynecologic oncologists, to determine the baseline capacity and to forecast visit capacity through 2020. Demand for visits was calculated by applying age-, sex-, and time-from-diagnosis-visit rate data from the National Cancer Institute's analysis of the 1998 to 2002 Surveillance, Epidemiology and End Results (SEER) database to the National Cancer Institute's cancer incidence and prevalence projections. The cancer incidence and prevalence projections were calculated by applying a 3-year average (2000–2002) of age- and sex-specific cancer rates from SEER to the US Census Bureau population projections released on March 2004. The baseline supply and demand forecasts assume no change in cancer care delivery and physician practice patterns. Alternate scenarios were constructed by changing assumptions in the baseline models. Results Demand for oncology services is expected to rise rapidly, driven by the aging and growth of the population and improvements in cancer survival rates, at the same time the oncology workforce is aging and retiring in increasing numbers. Demand is expected to rise 48% between 2005 and 2020. The supply of services provided by oncologists during this time is expected to grow more slowly, approximately 14%, based on the current age distribution and practice patterns of oncologists and the number of oncology fellowship positions. This translates into a shortage of 9.4 to 15.0 million visits, or 2,550 to 4,080 oncologists—roughly one-quarter to one-third of the 2005 supply. The baseline projections do not

Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling.

Science.gov (United States)

Wang, Ying; Branicky, Robyn; Noë, Alycia; Hekimi, Siegfried

2018-04-18

Superoxide dismutases (SODs) are universal enzymes of organisms that live in the presence of oxygen. They catalyze the conversion of superoxide into oxygen and hydrogen peroxide. Superoxide anions are the intended product of dedicated signaling enzymes as well as the byproduct of several metabolic processes including mitochondrial respiration. Through their activity, SOD enzymes control the levels of a variety of reactive oxygen species (ROS) and reactive nitrogen species, thus both limiting the potential toxicity of these molecules and controlling broad aspects of cellular life that are regulated by their signaling functions. All aerobic organisms have multiple SOD proteins targeted to different cellular and subcellular locations, reflecting the slow diffusion and multiple sources of their substrate superoxide. This compartmentalization also points to the need for fine local control of ROS signaling and to the possibility for ROS to signal between compartments. In this review, we discuss studies in model organisms and humans, which reveal the dual roles of SOD enzymes in controlling damage and regulating signaling. © 2018 Wang et al.

Sources and resources for oncologists to help answer the question: is PET/CT appropriate for my patient?

Science.gov (United States)

Karantanis, Dimitrios; Allen-Auerbach, Martin; Czernin, Johannes

2012-01-01

Positron emission tomography (PET)/computed tomography (CT)-subsequently referred to as PET/CT is emerging as a critically important diagnostic tool in oncology. There has been a substantial increase in the utilization of this modality over the last decade. The optimal imaging protocols are, however, still not established which results in considerable confusion and uncertainty among referring physicians and providers. Oncologists, hematologists and other physicians managing oncologic patients frequently face the dilemma of whether or not to order a PET/CT scan for their patients. The large body of evidence from clinical research often overwhelms the ability of physicians to stay adequately informed on the disease specific performance of PET/CT. Moreover, regulatory agencies have changed their requirements for reimbursement of PET/CT scans in an effort to curtail health care expenditures. In this article we attempt to inform users and providers about the appropriate use of this technology.

The impact of physician burnout on clinical and academic productivity of gynecologic oncologists: A decision analysis.

Science.gov (United States)

Turner, Taylor B; Dilley, Sarah E; Smith, Haller J; Huh, Warner K; Modesitt, Susan C; Rose, Stephen L; Rice, Laurel W; Fowler, Jeffrey M; Straughn, J Michael

2017-09-01

Physician burnout is associated with mental illness, alcohol abuse, and job dissatisfaction. Our objective was to estimate the impact of burnout on productivity of gynecologic oncologists during the first half of their career. A decision model evaluated the impact of burnout on total relative value (RVU) production during the first 15years of practice for gynecologic oncologists entering the workforce from 2011 to 2015. The SGO practice survey provided physician demographics and mean annual RVUs. Published data were used to estimate probability of burnout for male and female gynecologic oncologists, and the impact of depression, alcohol abuse, and early retirement. Academic productivity was defined as annual PubMed publications since finishing fellowship. Without burnout, RVU production for the cohort of 250 gynecologic oncologists was 26.2 million (M) RVUs over 15years. With burnout, RVU production decreased by 1.6 M (5.9% decrease). Disproportionate rates of burnout among females resulted in 1.1 M lost RVUs for females vs. 488 K for males. Academic production without burnout was estimated at 9277 publications for the cohort. Burnout resulted in 1383 estimated fewer publications over 15years (14.9%). The impact of burnout on clinical and academic productivity is substantial across all specialties. As health care systems struggle with human resource shortages, this study highlights the need for effective burnout prevention and wellness programs for gynecologic oncologists. Unless significant resources are designated to wellness programs, burnout will increasingly affect the care of our patients and the advancement of our field. Copyright © 2017 Elsevier Inc. All rights reserved.

National survey on prophylactic cranial irradiation: differences in practice patterns between medical and radiation oncologists

International Nuclear Information System (INIS)

Cmelak, Anthony J.; Choy, Hak; Shyr, Yu; Mohr, Peter; Glantz, Michael J.; Johnson, David H.

1999-01-01

Purpose: Prophylactic cranial irradiation (PCI) in the treatment of small cell lung cancer (SCLC) patients remains controversial in the oncology community because of its potential for long-term toxicity and unproven survival benefit in randomized trials. A national survey of 9176 oncologists was conducted to characterize the use of PCI with regard to physician demographics, patient characteristics, and oncologists' beliefs. Methods: Data was collected via a questionnaire letter survey. Biographical data, treatment patterns, and clinical impressions were analyzed by the generalized linear model and generalized estimating equations method. Results: There were 1231 responders overall (13.4% of those surveyed), including 628 (51%) radiation oncologists (RO), 587 (48%) medical oncologists (MO), 8 (0.6%) surgical oncologists, and 8 (0.6%) from other oncology subspecialties. Of respondents, 74% overall recommend PCI in limited-stage patients, including 65% of MO and 82% RO (p = 0.001). Of responders who recommend PCI in limited-stage patients, 67% do so only after complete response to initial therapy. Only 30% of respondents recommend PCI for extensive-stage SCLC patients (p = 0.001), and 94% of these recommend PCI only when those patients have a complete response after initial therapy. Interestingly, 38% of responding MO feel that PCI improves survival of limited-stage patients, but only 11% believe PCI improves quality of life. Of the RO, 48% believe PCI improves survival in limited-stage SCLC, and 36% feel PCI improves quality of life (p < 0.05 and p < 0.01, respectively). MO responders believe PCI causes late neurological sequelae more often than do RO responders (95% vs. 84%, p < 0.05), with impaired memory (37%), chronic fatigue (19%), and loss of motivation (13%) as most commonly seen side effects. Only 1.5% overall, however, routinely obtain neuropsychiatric testing in PCI patients, and 42% overall never obtain them. Conclusion: Results confirm that oncologic

[Comparison of set-up control for head and neck patients between radiation oncologist and therapists with the aim of partial delegation].

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Garcia-Ramirez, M; Maugey, S; Burgaud, L; Carpentey, F; Parezys, E; Carricaburu, M

2014-11-01

The aim of this prospective study was to evaluate daily set-up by a radiation oncologist and by radiation therapists using on-board imaging of patients with head and neck cancer in order to calculate margin to PTV (planning target volume) and intent partial delegation of positioning images control. The files of 11 patients with head and neck cancer treated on a Synergy™ (Elekta™) accelerator with on-board imaging system were evaluated. Daily kV-kV images were double-blind reviewed by radiation therapists (7 participants) and by one radiation oncologist. The radiation oncologist's measures were used for margin calculation from CTV to PTV. The difference of measures and the concordance of decisions between radiation therapists and the radiation oncologist were calculated. The 325 measures made by the radiation oncologist resulted in a margin of 5mm to be applied to the CTV in each direction. Nine hundred seventy-seven measures were made by the radiation oncologist and radiation therapists with a difference of 3mm or less in 98.46%. The concordance of decision for a 4mm difference or less to the isocenter was 96.7%. This study confirms the 5mm PTV margin mostly used in ORL. The small gap between the radiation oncologist's and therapists' measures allows a partial delegation of positioning images control. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Neoadjuvant long-course chemoradiation remains strongly favored over short-course radiotherapy by radiation oncologists in the United States.

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Mowery, Yvonne M; Salama, Joseph K; Zafar, S Yousuf; Moore, Harvey G; Willett, Christopher G; Czito, Brian G; Hopkins, M Benjamin; Palta, Manisha

2017-04-15

Short-course radiotherapy (SC-RT) and long-course chemoradiotherapy (LC-CRT) are accepted neoadjuvant treatments of rectal cancer. In the current study, the authors surveyed US radiation oncologists to assess practice patterns and attitudes regarding SC-RT and LC-CRT for patients with rectal cancer. The authors distributed a survey to 1701 radiation oncologists regarding treatment of neoadjuvant rectal cancer. Respondents were asked questions regarding the number of patients with rectal cancer treated, preference for SC-RT versus LC-CRT, and factors influencing regimen choice. Of 1659 contactable physicians, 182 responses (11%) were received. Approximately 83% treated at least 5 patients with rectal cancer annually. The majority of responding radiation oncologists (96%) preferred neoadjuvant LC-CRT for the treatment of patients with locally advanced rectal cancer and 44% never used SC-RT. Among radiation oncologists using SC-RT, respondents indicated they would not recommend this regimen for patients with low (74%) or bulky tumors (70%) and/or concern for a positive circumferential surgical resection margin (69%). The most frequent reasons for not offering SC-RT were insufficient downstaging for sphincter preservation (53%) and a desire for longer follow-up (45%). Many radiation oncologists indicated they would prescribe SC-RT for patients not receiving chemotherapy (62%) or patients with a geographic barrier to receiving LC-CRT (82%). Patient comorbidities appeared to influence regimen preferences for 79% of respondents. Approximately 20% of respondents indicated that altered oncology care reimbursement using capitated payment by diagnosis would impact their consideration of SC-RT. US radiation oncologists rarely use neoadjuvant SC-RT despite 3 randomized controlled trials demonstrating no significant differences in outcome compared with LC-CRT. Further research is necessary to determine whether longer follow-up coupled with the benefits of lower cost, increased

Po2 cycling protects diaphragm function during reoxygenation via ROS, Akt, ERK, and mitochondrial channels.

Science.gov (United States)

Zuo, Li; Pannell, Benjamin K; Re, Anthony T; Best, Thomas M; Wagner, Peter D

2015-12-01

Po2 cycling, often referred to as intermittent hypoxia, involves exposing tissues to brief cycles of low oxygen environments immediately followed by hyperoxic conditions. After experiencing long-term hypoxia, muscle can be damaged during the subsequent reintroduction of oxygen, which leads to muscle dysfunction via reperfusion injury. The protective effect and mechanism behind Po2 cycling in skeletal muscle during reoxygenation have yet to be fully elucidated. We hypothesize that Po2 cycling effectively increases muscle fatigue resistance through reactive oxygen species (ROS), protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and certain mitochondrial channels during reoxygenation. Using a dihydrofluorescein fluorescent probe, we detected the production of ROS in mouse diaphragmatic skeletal muscle in real time under confocal microscopy. Muscles treated with Po2 cycling displayed significantly attenuated ROS levels (n = 5; P ROS, Akt, ERK, as well as chemical stimulators to close mitochondrial ATP-sensitive potassium channel (KATP) or open mitochondrial permeability transition pore (mPTP). All these blockers or stimulators abolished improved muscle function with Po2 cycling treatment. This current investigation has discovered a correlation between KATP and mPTP and the Po2 cycling pathway in diaphragmatic skeletal muscle. Thus we have identified a unique signaling pathway that may involve ROS, Akt, ERK, and mitochondrial channels responsible for Po2 cycling protection during reoxygenation conditions in the diaphragm. Copyright © 2015 the American Physiological Society.

Decitabine induces delayed reactive oxygen species (ROS) accumulation in leukemia cells and induces the expression of ROS generating enzymes.

Science.gov (United States)

Fandy, Tamer E; Jiemjit, Anchalee; Thakar, Manjusha; Rhoden, Paulette; Suarez, Lauren; Gore, Steven D

2014-03-01

Azanucleoside DNA methyltransferase (DNMT) inhibitors are currently approved by the U.S. Food and Drug Administration for treatment of myelodysplastic syndrome. The relative contributions of DNMT inhibition and other off-target effects to their clinical efficacy remain unclear. Data correlating DNA methylation reversal and clinical response have been conflicting. Consequently, it is necessary to investigate so-called off-target effects and their impact on cell survival and differentiation. Flow cytometry was used for cell cycle, apoptosis, and reactive oxygen species (ROS) accumulation analysis. Gene expression analysis was performed using real-time PCR. DNA methylation was detected by methylation-specific PCR. Mitochondrial membrane potential was analyzed using JC-1 dye staining. Western blotting was used for quantitative protein expression analysis. 5-Aza-2'-deoxycytidine (DAC) induced cell-cycle arrest and apoptosis in leukemia cells. p53 expression was dispensable for DAC-induced apoptosis. DAC induced delayed ROS accumulation in leukemia cells but not in solid tumor cells and p53 expression was dispensable for ROS increase. ROS increase was deoxycytidine kinase dependent, indicating that incorporation of DAC into nuclear DNA is required for ROS generation. ROS accumulation by DAC was caspase-independent and mediated the dissipation of the mitochondrial membrane potential. Concordantly, ROS scavengers diminished DAC-induced apoptosis. DAC induced the expression of different NADPH oxidase isoforms and upregulated Nox4 protein expression in an ATM-dependent manner, indicating the involvement of DNA damage signaling in Nox4 upregulation. These data highlight the importance of mechanisms other than DNA cytosine demethylation in modulating gene expression and suggest investigating the relevance of ROS accumulation to the clinical activity of DAC. ©2014 AACR

Demodicidosis en pacientes con rosácea

Directory of Open Access Journals (Sweden)

Edhizon Trejo Mucha

2007-01-01

Full Text Available Objetivo: Determinar la frecuencia de demodicidosis y sus características clínicas en pacientes con rosácea. Materiales y métodos: Estudio de casos y controles en 42 pacientes con rosácea y 42 controles para describir la presencia y densidad de D. folliculorum. El estudio se realizó en el Hospital Nacional Cayetano Heredia entre marzo y setiembre del 2004, utilizándose la técnica de Tello. Resultados: Demodex folliculorum fue encontrado en los 42 pacientes con rosácea (100% y en 13 (31,0% del grupo control, (p= 0,000. La exposición a gatos, la crianza de roedores y cerdos, la seborrea y el uso de corticoides tópicos fueron mas frecuentes en los pacientes con rosácea. Conclusiones: La presencia de Demodex folliculorum fue más frecuente en los pacientes con rosácea. (Rev Med Hered 2007;18:15-21.

Satisfaction with work-life balance among U.S. gynecologic oncologists, a cross-sectional study.

Science.gov (United States)

Szender, J Brian; Grzankowski, Kassondra S; Eng, Kevin H; Lele, Shashikant B; Odunsi, Kunle; Frederick, Peter J

To evaluate the satisfaction with work-life balance (WLB) and career satisfaction of gynecologic oncologists. In August 2014, members of the Society of Gynecologic Oncology (SGO) were sent an anonymous, cross-sectional survey evaluating demographic variables, practice characteristics, career satisfaction, fatigue, and satisfaction with WLB. Fatigue was assessed using a visual-analog scale. Career satisfaction and WLB were assessed with a Likert scale. Inferential statistics were computed with type I error rates of 0.05. Out of the 1002 gynecologic oncologists surveyed, 290 (28.9%) responded. Only 18.6% of respondents were satisfied with WLB and there were significant associations between gender (P = 0.0157), time spent in work related activities at home (P = 0.0024), on weekends (P = 0.0017), and in the hospital (P = 0.0001). More than 84% of physicians reported they would choose medicine as a career again and of those 90% would choose to be a gynecologic oncologist again. Fatigue was strongly associated with dissatisfaction with WLB in univariate and multivariate analysis (P satisfaction may assist the SGO in meeting future gynecologic cancer care needs.

Endogenous mechanisms of reactive oxygen species (ROS generation

Directory of Open Access Journals (Sweden)

Agata Sarniak

2016-11-01

Full Text Available The main cellular source of reactive oxygen species (ROS is mitochondrial respiratory chain and active NADPH responsible for “respiratory burst” of phagocytes. Whatsmore ROS are produced in endoplasmic reticulum, peroxisomes, with the participation of xanthine and endothelial oxidase and during autoxidation process of small molecules. Mitochondrial respiratory chain is the main cellular source of ROS. It is considered that in aerobic organisms ROS are mainly formed during normal oxygen metabolism, as byproducts of oxidative phosphorylation, during the synthesis of ATP. The intermembranous phagocyte enzyme – activated NADPH oxidase, responsible for the “respiratory burst” of phagocytes, which is another source of ROS, plays an important role in defense of organism against infections.The aim of this article is to resume actuall knowledge about structure and function of the mitochondrial electron transport chain in which ROS are the byproducts and about NADPH oxidase as well as the function of each of its components in the “respiratory burst” of phagocytes.

A reaction-diffusion model of ROS-induced ROS release in a mitochondrial network.

Directory of Open Access Journals (Sweden)

Lufang Zhou

2010-01-01

Full Text Available Loss of mitochondrial function is a fundamental determinant of cell injury and death. In heart cells under metabolic stress, we have previously described how the abrupt collapse or oscillation of the mitochondrial energy state is synchronized across the mitochondrial network by local interactions dependent upon reactive oxygen species (ROS. Here, we develop a mathematical model of ROS-induced ROS release (RIRR based on reaction-diffusion (RD-RIRR in one- and two-dimensional mitochondrial networks. The nodes of the RD-RIRR network are comprised of models of individual mitochondria that include a mechanism of ROS-dependent oscillation based on the interplay between ROS production, transport, and scavenging; and incorporating the tricarboxylic acid (TCA cycle, oxidative phosphorylation, and Ca(2+ handling. Local mitochondrial interaction is mediated by superoxide (O2.- diffusion and the O2.(--dependent activation of an inner membrane anion channel (IMAC. In a 2D network composed of 500 mitochondria, model simulations reveal DeltaPsi(m depolarization waves similar to those observed when isolated guinea pig cardiomyocytes are subjected to a localized laser-flash or antioxidant depletion. The sensitivity of the propagation rate of the depolarization wave to O(2.- diffusion, production, and scavenging in the reaction-diffusion model is similar to that observed experimentally. In addition, we present novel experimental evidence, obtained in permeabilized cardiomyocytes, confirming that DeltaPsi(m depolarization is mediated specifically by O2.-. The present work demonstrates that the observed emergent macroscopic properties of the mitochondrial network can be reproduced in a reaction-diffusion model of RIRR. Moreover, the findings have uncovered a novel aspect of the synchronization mechanism, which is that clusters of mitochondria that are oscillating can entrain mitochondria that would otherwise display stable dynamics. The work identifies the

ROS - Robotiikan tutkimustyökalusta kohti kaupallista menestystarinaa

OpenAIRE

Ahonen, Mika

2017-01-01

Avoimen lähdekoodin ROS-käyttöjärjestelmä on yleisesti tutkimushankkeissa käytetty robotiikan kehitysalusta. Tutkielman tavoitteena on ollut arvioida onko ROS järjestelmä, joka tulee yleistymään myös robotiikan kaupallisissa ratkaisuissa. ROS-pohjaisia kaupallisia tuotteita on jo olemassa ja sen käyttöä on pilotoitu runsaasti erilaisilla sovellusalueilla. Erityisesti palvelu- ja pilvirobotiikan alueilla ROSilla on kasvavaa potentiaalia. ROS on vielä kehittyvä järjestelmä ja ei nykyisellään...

Survey of Medical Oncology Status in Korea (SOMOS-K): A National Survey of Medical Oncologists in the Korean Association for Clinical Oncology (KACO).

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Kim, Do Yeun; Lee, Yun Gyoo; Kim, Bong-Seog

2017-07-01

This study was conducted to investigate the current role of medical oncologists in cancer care with a focus on increasing the recognition of medical oncology as an independent specialty. Questionnaires modified from the Medical Oncology Status in Europe Survey dealing with oncology structure, resources, research, and patterns of care given by medical oncologists were selected. Several modifications were made to the questionnaire after feedback from the insurance and policy committee of the Korean Association for Clinical Oncology (KACO). The online survey was then sent to KACO members. A total of 214 medical oncologists (45.8% of the total inquiries), including 71 directors of medical oncology institutions, took the survey. Most institutions had various resources, including a medical oncology department (94.1%) and a department of radiation oncology (82.4%). There was an average of four medical oncologists at each institution. Medical oncologists were involved in various treatments from diagnosis to end-of-life care. They were also chemotherapy providers from a wide range of institutions that treated many types of solid cancers. In addition, 86.2% of the institutions conducted research. This is the first national survey in Korea to show that medical oncologists are involved in a wide range of cancer treatments and care. This survey emphasizes the contributions and proper roles of medical oncologists in the evolving health care environment in Korea.

Optimizing the Universal Robots ROS driver

DEFF Research Database (Denmark)

Andersen, Thomas Timm

improvement both in terms of faster reaction as well as making it possible to control the robot using either ros_control or ordinary joint speed commands, which is required for many types of sensory based control like visual servoing. The developed driver is compared to the drivers already existing in the ROS...

Professional Burnout in European Young Oncologists

DEFF Research Database (Denmark)

Banerjee, Sutanuka; Califano, R; Corral, Javier

2017-01-01

≤40 (YOs). Methods: A survey was conducted using the validated Maslach Burnout Inventory (MBI) and additional questions exploring work/lifestyle factors. Statistical analyses were performed to identify factors associated with burnout. Results: 737 surveys (all ages) were collected from 41 European......Background: Burnout in health care professionals could have serious negative consequences on quality of patient care, professional satisfaction and personal life. Our aim was to investigate the burnout prevalence, work and lifestyle factors potentially affecting burnout amongst European oncologists...... = 0.0001 ) and low accomplishment was highest in the 26-30 age group ( p work/life balance, access to support services, living alone and inadequate vacation time remained independent burnout factors ( p 

Impact of poster presentations on academic knowledge transfer from the oncologist perspective in Turkey.

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Arslan, Deniz; Koca, Timur; Tastekin, Didem; Basaran, Hamit; Bozcuk, Hakan

2014-01-01

Currently poster presentations offer a common visual medium for knowledge transfer by a wide range of health professionals. Our study aimed to determine the scientific importance of poster presentations for Medical and Radiation Oncologists. A survey form including 40 questions was distributed to a total of 131 oncologists experienced in poster presentations. One hundred completed survey forms were included in the study. Descriptive statistics and modified thematic analyses were performed on the responses. Overall 64% of the participants agreed that posters were a good medium for knowledge transfer. Some 88% agreed that concise and clear styled presentations would increase appealing interests for poster contents. Visual appearance was cited more influential than content of the subject; 70% of participants agreed that appearances of posters could help to draw more viewer attention. Of respondents, 63% believed that posters accompanied by their author were more attractive for congress attendees, and 33% of them declared that the halo effect of the poster presenter was also important. The present study indicated that intelligibility, appearance and visuality of posters are most important factors from the aspect of oncologist participants. Presenters must take into account these important points when preparing their academic posters.

Controversies in oncologist-patient communication: a nuanced approach to autonomy, culture, and paternalism.

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Cherny, Nathan I

2012-01-01

Difficult dialogues with patients facing life-changing decisions are an intrinsic part of oncologic practice and a major source of stress. Having a sophisticated approach to the concepts of autonomy, paternalism, and culture can help in addressing difficult dilemmas that arise around the issues of disclosure and decision making. This article addresses some of the most common major challenges in oncologist-patient communication with a nuanced approach to the concepts of autonomy, paternalism, and culture. It introduces the new concept of"voluntary diminished autonomy" and describes the implications this concept has for the consent process. It also attempts to bring clarity to common problems and misconceptions relating to culture, paternalism, and therapeutic privilege as these pertain to the communication practices of oncologists.

SkiROS

DEFF Research Database (Denmark)

Rovida, Francesco; Schou, Casper; Andersen, Rasmus Skovgaard

During the last decades, the methods for intuitive task level programming of robots have become a fundamental point of interest for industrial application. The paper in hand presents SkiROS (Skill-based Robot Operating System) a novel software architecture based on the skills paradigm. The skill ...... of a flexible, highly modular system for the development of cognitive robot tasks....

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

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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.

Survey of Michigan dentists and radiation oncologists on oral care of patients undergoing head and neck radiation therapy.

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Patel, Yoshita; Bahlhorn, Hannah; Zafar, Saniya; Zwetchkenbaum, Samuel; Eisbruch, Avraham; Murdoch-Kinch, Carol Anne

2012-07-01

Oral complications of radiation therapy for head and neck cancer (HNC) are associated with a significant decline in oral health-related quality of life (OHQOL). The dentist, working with the radiation oncologist and the rest of the health care team, plays an important role in the prevention and management of these complications, but patients do not always receive care consistent with current guidelines. This study investigated barriers to recommended care. There is variability in knowledge and practice among dentists and radiation oncologists regarding the dental management of patients treated with head and neck radiotherapy (HNRT), and inadequate communication and collaboration between members of the patient's health care team contribute to inconsistencies in application of clinical care guidelines. There is on interest and need for continuing dental (CDE) and medical education (CME) on this topic. A questionnaire was developed to assess dentists' knowledge and practice of dental management of HNC patients and their interest in CDE on this topic. All members of the Michigan Dental Association (MDA) with email addresses were asked to complete the survey online, and a random sample of MDA members without email addresses was invited to complete a paper version of the same survey. All Michigan members of the American Society for Radiation Oncology (ASTRO) were invited to complete an online version of the survey modified for radiation oncologists. The response rate for dentists was 47.9% and radiation oncologists was 22.3%. Of the dentists who responded, 81% reported that a major barrier to providing dental treatment before radiotherapy was a lack of time between initial dental consultation and the start of radiation; inadequate communication between health care providers was blamed most frequently for this. Ten percent of the dentists and 25% of the radiation oncologists reported that they did not treat HNC patients because they lacked adequate training, and 55% of

A Qualitative Study of Medical Oncologists' Experiences of Their Profession and Workforce Sustainability.

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Alex Broom

Full Text Available Medical oncology is a steadily evolving field of medical practice and professional pathway for doctors, offering value, opportunity and challenge to those who chose this medical specialty. This study examines the experiences of a group of Australian medical oncologists, with an emphasis on their professional practice, career experiences, and existing and emerging challenges across career stages.In-depth qualitative interviews were conducted with 22 medical oncologists, including advanced trainees, early-career consultants and senior consultants, focusing on: professional values and experiences; career prospects and pathways; and, the nexus of the characteristics of the profession and delivery of care.The following themes were emergent from the interviews: the need for professional reinvention and the pressure to perform; the importance, and often absence, of mentoring and feedback loops; the emotional labour of oncology; and, the impact of cascading workload volume on practice sustainability.Understanding professional experiences, career trajectories and challenges at the workforce level are crucial for understanding what drives the oncological care day-to-day. The results indicate that there are considerable potential tensions between the realities of professional, workforce demands and expectations for patient care. Such tensions have real and significant consequences on individual medical oncologists with respect to their futures, aspirations, satisfaction with work, caring practices, interactions with patients and potentially therapeutic outcomes.

Literature-based discovery of diabetes- and ROS-related targets

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Pande Manjusha

2010-10-01

Full Text Available Abstract Background Reactive oxygen species (ROS are known mediators of cellular damage in multiple diseases including diabetic complications. Despite its importance, no comprehensive database is currently available for the genes associated with ROS. Methods We present ROS- and diabetes-related targets (genes/proteins collected from the biomedical literature through a text mining technology. A web-based literature mining tool, SciMiner, was applied to 1,154 biomedical papers indexed with diabetes and ROS by PubMed to identify relevant targets. Over-represented targets in the ROS-diabetes literature were obtained through comparisons against randomly selected literature. The expression levels of nine genes, selected from the top ranked ROS-diabetes set, were measured in the dorsal root ganglia (DRG of diabetic and non-diabetic DBA/2J mice in order to evaluate the biological relevance of literature-derived targets in the pathogenesis of diabetic neuropathy. Results SciMiner identified 1,026 ROS- and diabetes-related targets from the 1,154 biomedical papers (http://jdrf.neurology.med.umich.edu/ROSDiabetes/. Fifty-three targets were significantly over-represented in the ROS-diabetes literature compared to randomly selected literature. These over-represented targets included well-known members of the oxidative stress response including catalase, the NADPH oxidase family, and the superoxide dismutase family of proteins. Eight of the nine selected genes exhibited significant differential expression between diabetic and non-diabetic mice. For six genes, the direction of expression change in diabetes paralleled enhanced oxidative stress in the DRG. Conclusions Literature mining compiled ROS-diabetes related targets from the biomedical literature and led us to evaluate the biological relevance of selected targets in the pathogenesis of diabetic neuropathy.

Polymorphic ROS scavenging revealed by CCCP in a lizard

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Olsson, Mats; Wilson, Mark; Isaksson, Caroline; Uller, Tobias

2009-07-01

Ingestion of antioxidants has been argued to scavenge circulating reactive molecules (e.g., free radicals), play a part in mate choice (by mediating access to this important resource), and perhaps increase life span. However, recent work has come to question these relationships. We have shown elsewhere in the polychromatic lizard, Ctenophorus pictus, that diet supplementation of carotenoids as antioxidants does not depress circulating natural reactive oxygen species (ROS) levels and leads to no corresponding improvement of color traits. However, a much stronger test would be to experimentally manipulate the ROS levels themselves and assess carotenoid-induced ROS depression. Here, we achieve this by using carbonyl cyanide 3-chlorophenylhydrazone, which elevates superoxide (SO) formation approximately threefold at 10 μM in this model system. We then look for depressing effects on ROS of the carotenoids in order to assess whether ‘super-production’ of SO makes carotenoid effects on elevated ROS levels detectable. The rationale for this treatment was that if not even such elevated levels of SO are reduced by carotenoid supplementation, the putative link carotenoids, ROS depression, and mate quality (in terms of antioxidant capacity) is highly questionable. We conclude that there is no significant effect of carotenoids on mean SO levels even at the induced ROS levels. However, our results showed a significant interaction effect between carotenoid treatment and male color, with red males having higher ROS levels than yellow males. We suggest that this may be because different pigments are differently involved in the generation of the integumental colors in the two morphs with concomitant effects on ROS depletion depending on carotenoid uptake or allocation to coloration and antioxidation.

The reality of economics for oncologists.

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Taylor, David

2017-06-01

This article outlines the historical development of health economics and its present role in oncology related health technology assessments (HTAs). Despite concerns about the prices and immediate costs of new anticancer medicines for indications such as breast cancer overall spending on such treatments is affordable and offers long term value for money in countries such as the US, Canada and those of Western Europe. Oncologists wishing to protect the interests of current and future patients with both advanced and earlier stage cancers may be regarded as having a responsibility to understand the nature of health economic evaluations, and to be actively involved in decisions affecting access to current treatments and future levels of investment in incrementally improving therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Perceptions of Radiation Oncologists and Urologists on Sources and Type of Evidence to Inform Prostate Cancer Treatment Decisions

International Nuclear Information System (INIS)

Han, Leona C.; Delpe, Sophia; Shah, Nilay D.; Ziegenfuss, Jeanette Y.; Tilburt, Jon C.; Karnes, R. Jeffrey; Nguyen, Paul L.; Gross, Cary P.; Yu, James B.; Trinh, Quoc-Dien; Sun, Maxine; Ranasinghe, Weranja K.B.; Kim, Simon P.

2014-01-01

Purpose: To perform a national survey of radiation oncologists and urologists about the type of resources used and the level of evidence needed to change clinical practice in localized prostate cancer. Methods and Materials: From a random sample, 1422 physicians were mailed a survey assessing the types of information used and what level of evidence could alter their clinical practice in prostate cancer. Multivariable logistic regression models were used to identify differences in physician characteristics for each outcome. Results: Survey response rates were similar for radiation oncologists and urologists (44% vs 46%; P=.46). Specialty-specific journals represented the most commonly used resource for informing the clinical practice for radiation oncologists (65%) and urologists (70%). Relative to radiation oncologists, urologists were less likely to report utilizing top-tier medical journals (25% vs 39%; adjusted odds ratio [OR] 0.50; P=.01) or cancer journals (22% vs 51%; adjusted OR 0.50; P<.001) but more likely to rely on clinical guidelines (46% vs 38%; adjusted OR 1.6; P=.006). Both radiation oncologists and urologists most commonly reported large randomized, clinical trials as the level of evidence to change treatment recommendations for localized prostate cancer (85% vs 77%; P=.009). Conclusions: Both specialties rely on their own specialty-specific journals and view randomized, clinical trials as the level of evidence needed to change clinical practice. Our study provides a context on meaningful ways of disseminating evidence for localized prostate cancer

Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction.

Science.gov (United States)

Resseguie, Emily A; Staversky, Rhonda J; Brookes, Paul S; O'Reilly, Michael A

2015-08-01

High levels of oxygen (hyperoxia) are often used to treat individuals with respiratory distress, yet prolonged hyperoxia causes mitochondrial dysfunction and excessive reactive oxygen species (ROS) that can damage molecules such as DNA. Ataxia telangiectasia mutated (ATM) kinase is activated by nuclear DNA double strand breaks and delays hyperoxia-induced cell death through downstream targets p53 and p21. Evidence for its role in regulating mitochondrial function is emerging, yet it has not been determined if mitochondrial dysfunction or ROS activates ATM. Because ATM maintains mitochondrial homeostasis, we hypothesized that hyperoxia induces both mitochondrial dysfunction and ROS that activate ATM. In A549 lung epithelial cells, hyperoxia decreased mitochondrial respiratory reserve capacity at 12h and basal respiration by 48 h. ROS were significantly increased at 24h, yet mitochondrial DNA double strand breaks were not detected. ATM was not required for activating p53 when mitochondrial respiration was inhibited by chronic exposure to antimycin A. Also, ATM was not further activated by mitochondrial ROS, which were enhanced by depleting manganese superoxide dismutase (SOD2). In contrast, ATM dampened the accumulation of mitochondrial ROS during exposure to hyperoxia. Our findings suggest that hyperoxia-induced mitochondrial dysfunction and ROS do not activate ATM. ATM more likely carries out its canonical response to nuclear DNA damage and may function to attenuate mitochondrial ROS that contribute to oxygen toxicity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma

International Nuclear Information System (INIS)

Lee, Kyung-Hun; Lee, Kyoung-Bun; Kim, Tae-Yong; Han, Sae-Won; Oh, Do-Youn; Im, Seock-Ah; Kim, Tae-You; Yi, Nam-Joon; Lee, Kwang-Woong; Suh, Kyung-Suk; Jang, Ja-June; Bang, Yung-Jue

2015-01-01

More knowledge about genetic and molecular features of cholangiocarcinoma is needed to develop effective therapeutic strategies. We investigated the clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma. One hundred ninety-four patients with curatively resected intrahepatic cholangiocarcinoma were included in this study. Tumor tissue specimens were collected and analyzed for ROS1 gene rearrangement using fluorescence in situ hybridization (FISH) and ROS1 protein expression using immunohistochemistry (IHC). ROS1 immunohistochemistry was positive (moderate or strong staining) in 72 tumors (37.1 %). ROS1 protein expression was significantly correlated with well differentiated tumors, papillary or mucinous histology, oncocytic/hepatoid or intestinal type tumors, and periductal infiltrating or intraductal growing tumors (vs. mass-forming cholangiocarcinoma). ROS-expressing tumors were associated with better disease-free survival (30.1 months for ROS1 expression (+) tumors vs. 9.0 months for ROS1 (−) tumors, p = 0.006). Moreover, ROS1 expression was an independent predictor of better disease-free survival in a multivariate analysis (HR 0.607, 95 % CI 0.377–0.976; p = 0.039). Although break-apart FISH was successfully performed in 102 samples, a split pattern indicative of ROS1 gene rearrangement was not found in the examined samples. ROS1 protein expression was associated with well-differentiated histology and better survival in our patients with resected intrahepatic cholangiocarcinoma. ROS1 gene rearrangement by break-apart FISH was not found in the examined samples

The role of ASTRO and the radiation oncologist in preparedness

International Nuclear Information System (INIS)

Daly, N.

2003-01-01

The events on September 11, 2001 were unpredictable and tragic, however it is not inconceivable that a similar terrorist event could occur again, this time involving radiologic or nuclear material. In order to prepare for this American Society for Therapeutic Radiology and Oncology (ASTRO) convened a task force. Initially the task force worked with the American College of Radiology (ACR)and the American Society of Physicists in Medicine (AAPM)to publish a PRIMER entitled 'Disaster Preparedness for Radiology Professionals'. The PRIMER serve as a quick reference in the event of a radiation disaster and is available on the ASTRO Web site (www.astro.org). The task force has also developed a detailed and extensive training program, in partnership with the U.S. Department of Energy's Radiation Emergency Assistance Center/Training Site (REAC/TS) in Oak Ridge (TN), that will equip radiation oncologists with the necessary expertise to train hospital radiation oncology departments and other healthcare personnel who are responsible for implementing and carrying out hospital planning for disasters involving radioactive materials. This presentation will outline the effort ASTRO has been involved with since September 11, 2001 to prepare the professional community it represent in the event of a radiation/nuclear disaster

Managing an Older Adult with Cancer: Considerations for Radiation Oncologists

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Sanders Chang

2017-01-01

Full Text Available Older adults with cancer present a unique set of management complexities for oncologists and radiation oncologists. Prognosis and resilience to cancer treatments are notably dependent on the presence or risk of “geriatric syndromes,” in addition to cancer stage and histology. Recognition, proper evaluation, and management of these conditions in conjunction with management of the cancer itself are critical and can be accomplished by utilization of various geriatric assessment tools. Here we review principles of the geriatric assessment, common geriatric syndromes, and application of these concepts to multidisciplinary oncologic treatment. Older patients may experience toxicities related to treatments that impact treatment effectiveness, quality of life, treatment-related mortality, and treatment compliance. Treatment-related burdens from radiotherapy are increasingly important considerations and include procedural demands, travel, costs, and temporary or permanent loss of functional independence. An overall approach to delivering radiotherapy to an older cancer patient requires a comprehensive assessment of both physical and nonphysical factors that may impact treatment outcome. Patient and family-centered communication is also an important part of developing a shared understanding of illness and reasonable expectations of treatment.

Screening for ROS1 gene rearrangements in non-small cell lung cancers using immunohistochemistry with FISH confirmation is an effective method to identify this rare target

Science.gov (United States)

Selinger, Christina I; Li, Bob T; Pavlakis, Nick; Links, Matthew; Gill, Anthony J; Lee, Adrian; Clarke, Stephen; Tran, Thang N; Lum, Trina; Yip, Po Yee; Horvath, Lisa; Yu, Bing; Kohonen-Corish, Maija RJ; O’Toole, Sandra A; Cooper, Wendy A

2016-01-01

Aims To assess the prevalence of ROS1 rearrangements in a retrospective and prospective diagnostic Australian cohort and evaluate the effectiveness of immunohistochemical screening. Methods A retrospective cohort of 278 early stage lung adenocarcinomas and an additional 104 prospective NSCLC cases referred for routine molecular testing were evaluated. ROS1 immunohistochemistry (IHC) was performed (D4D6 clone, Cell Signaling Technology) on all cases as well as fluorescence in situ hybridisation (FISH) using the ZytoVision and Abbott Molecular ROS1 FISH probes, with ≥15% of cells with split signals considered positive for rearrangement. Results Eighty eight cases (32%) from the retrospective cohort showed staining by ROS1 IHC, and one case (0.4%) showed ROS1 rearrangement by FISH. Nineteen of the prospective diagnostic cases showed ROS1 IHC staining of which 12 (12%) cases were confirmed as ROS1 rearranged by FISH. There were no ROS1 rearranged cases that showed no expression of ROS1 with IHC. The ROS1 rearranged cases in the prospective cohort were all EGFR wildtype and ALK rearrangement negative. The sensitivity of ROS1 IHC in the retrospective cohort was 100% and specificity was 76%. Conclusions ROS1 rearrangements are rare events in lung adenocarcinomas. Selection of cases for ROS1 FISH testing, by excluding EGFR/ALK positive cases and use of IHC to screen for potentially positive cases can be used to enrich for the likelihood of a identifying a ROS1 rearranged lung cancer and prevent the need to undertake expensive and time consuming FISH testing in all cases. PMID:27599111

Recovery opportunities, work-home conflict, and emotional exhaustion among hematologists and oncologists in private practice.

Science.gov (United States)

Nitzsche, Anika; Neumann, Melanie; Groß, Sophie E; Ansmann, Lena; Pfaff, Holger; Baumann, Walter; Wirtz, Markus; Schmitz, Stephan; Ernstmann, Nicole

2017-04-01

Hematologists and oncologists in private practice play a central role in the care provided for cancer patients. The present study analyzes stress and relaxation aspects in the work of hematologists and oncologists in private practice in Germany in relation to emotional exhaustion, as a core dimension of burnout syndrome. The study focuses on the opportunities for internal recovery using breaks and time out during the working day, the frequency of working on weekends and on vacation, and the physician's work-home and home-work conflict. Postulated associations between the constructs were analyzed using a structural equation model. If work leads to conflicts in private life (work-home conflict), it is associated with greater emotional exhaustion. Working frequently at the weekend is associated with greater work-home conflict and indirectly with greater emotional exhaustion. By contrast, the availability of opportunities to relax and recover during the working day is associated with less work-home conflict and indirectly with less emotional exhaustion. These results underline the importance of internal recovery opportunities during the working day and a successful interplay between working and private life for the health of outpatient hematologists and oncologists.

Pediatric oncologist willingness to offer germline TP53 testing in osteosarcoma.

Science.gov (United States)

Shaul, Eliana; Roth, Michael; Lo, Yungtai; Geller, David S; Hoang, Bang; Yang, Rui; Malkin, David; Gorlick, Richard; Gill, Jonathan

2018-03-15

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by mutations in the tumor-suppressor gene TP53. Osteosarcoma is a sentinel cancer in LFS. Prior studies using Sanger sequencing platforms have demonstrated that 3% of individuals with osteosarcoma harbor a mutation in TP53. New data from next-generation sequencing have demonstrated that 3.8% of patients with osteosarcoma have a known pathogenic variant, and an additional 5.7% carry exonic variants of unknown significance in TP53. Pediatric oncologists were e-mailed an anonymous 18-question survey assessing their willingness to offer TP53 germline testing to a child with osteosarcoma with or without a family history, and they were evaluated for changes in their choices with the prior data and the new data. One hundred seventy-seven pediatric oncologists (22%) responded to the survey. Respondents were more likely to offer TP53 testing to a patient with a positive family history (77.4% vs 12.4%; P offer TP53 testing once they were provided with the new data (25.4% vs 12.4%; P = .0038). The proportion of providers who responded that they were unsure increased significantly when they were presented with the new data (25.4% vs 10.2%; P = .0002). Potential implications for other family members and the possibility that surveillance imaging would detect new malignancies at an earlier stage were important factors influencing a provider's decision to offer TP53 testing. Recent data increase the proportion of providers willing to offer testing, and this suggests concern on the part of pediatric oncologists that variants of unknown significance may be disease-defining in rare cancers. Cancer 2018;124:1242-50. © 2018 American Cancer Society. © 2018 American Cancer Society.

Regulation of ROS in transmissible gastroenteritis virus-activated apoptotic signaling

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Ding, Li [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China); College of Life Sciences, Hainan Normal University, Haikou, Hainan 571158 (China); Zhao, Xiaomin; Huang, Yong; Du, Qian; Dong, Feng; Zhang, Hongling; Song, Xiangjun; Zhang, Wenlong [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China); Tong, Dewen, E-mail: dwtong@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China)

2013-12-06

Highlights: •TGEV infection induced ROS accumulation. •ROS accumulation is involved in TGEV-induced mitochondrial integrity impairment. •ROS is associated with p53 activation and apoptosis occurrence in TGEV-infected cells. -- Abstract: Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, causes severe lethal watery diarrhea and dehydration in piglets. Previous studies indicate that TGEV infection induces cell apoptosis in host cells. In this study, we investigated the roles and regulation of reactive oxygen species (ROS) in TGEV-activated apoptotic signaling. The results showed that TGEV infection induced ROS accumulation, whereas UV-irradiated TGEV did not promote ROS accumulation. In addition, TGEV infection lowered mitochondrial transmembrane potential in PK-15 cell line, which could be inhibited by ROS scavengers, pyrrolidinedithiocarbamic (PDTC) and N-acetyl-L-cysteine (NAC). Furthermore, the two scavengers significantly inhibited the activation of p38 MAPK and p53 and further blocked apoptosis occurrence through suppressing the TGEV-induced Bcl-2 reduction, Bax redistribution, cytochrome c release and caspase-3 activation. These results suggest that oxidative stress pathway might be a key element in TGEV-induced apoptosis and TGEV pathogenesis.

Key diagnostic information for the oncologist

International Nuclear Information System (INIS)

Zlatareva, D.

2012-01-01

Full text: The radiologists use many modalities for imaging of oncologic patients. In order to get the most out of these imaging studies oncologist have to provide with precise information: what is the working diagnosis, what treatment the patients has had and what is the clinical question should be answered by imaging study. The main indications for imaging are confirmation of diagnosis, evaluation of the patient for surgery or assessment of response to the therapy. These will influence the choice of the test, the protocol and interpretation of the results. Imaging plays a vital role in the management of patients with cancer. It is important not only for diagnosis, indicating sites of abnormality, and guiding biopsies, but it is also crucial in assessing disease extent and thereby determining treatment. The stage of cancer at the time of diagnosis is a key factor to define prognosis and is important element in determining appropriate treatment. The most clinically used cancer staging system is tumor node metastasis (TNM). Stage is determined from information on the tumor, regional nodes, and metastases and by grouping cases with similar prognosis. The criteria for defining anatomic extent of disease are specific for tumors at different anatomic sites and of different histologic types. Therefore, the criteria for T, N and M are defined separately for each tumor and histologic type. For Hodgkin and other lymphomas, a different system for the extent of disease and prognosis is used. It is mandatory for the radiologist to learn TNM system to provide the oncologist with key diagnostic information. Learning objectives: To understand TNM staging system for the most common malignancies To review the changes from the sixth to the seven edition of the American Joint committee on cancer staging manual To describe diagnostic information provided by CT and MRI in preoperative planning and after therapy To discuss the role of PET/CT imaging in oncology

Oncologists' communication about end of life: the relationship among secondary traumatic stress, compassion satisfaction, and approach and avoidance communication.

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Granek, Leeat; Nakash, Ora; Cohen, Michal; Ben-David, Merav; Ariad, Samuel

2017-11-01

Oncologists must communicate effectively with patients and their families about end of life (EOL). Despite the importance of communicating on this topic, many oncologists avoid these conversations. The objective of this study was to examine the associations between secondary traumatic stress and compassion satisfaction and approach and avoidant communication about EOL with cancer patients. A convenience sample of 79 oncologists (n = 27 men, n = 52 women) participated in the study. Oncologists completed a survey that included a sociodemographic and clinical information questionnaire, the Professional Quality of Life Scale, and Communication about End of Life Survey. To examine the effect of secondary traumatic stress and compassion satisfaction on approach and avoidant communication, while controlling for gender and age, 2 hierarchical linear regression analyses were computed. Oncologists reported high levels of secondary traumatic stress and high compassion satisfaction. Scores on the approach and avoidant communication scales were in the mid-range of the scale. Lower reports of secondary traumatic stress and higher compassion satisfaction were associated with higher approach communication strategies: however, only higher secondary traumatic stress was associated with higher avoidant communication strategies. Our findings indicate that there is an association between emotional factors and approach communication. The findings have clinical implications in designing effective communication skills training. Further research and training should take secondary traumatic stress and compassion satisfaction into consideration to be able to ensure that terminal patients and their families receive the best quality EOL care. Copyright © 2016 John Wiley & Sons, Ltd.

ROS and myokines promote muscle adaptation to exercise

DEFF Research Database (Denmark)

Scheele, Camilla; Nielsen, Søren; Pedersen, Bente K

2009-01-01

in skeletal muscle. In fact, it seems that exercise-induced ROS are able to stimulate cytokine production from skeletal muscle. Despite the initial view that ROS were potentially cell damaging, it now seems possible that these substances have important roles in the regulation of cell signaling. Muscle......-derived cytokines, so-called 'myokines', are distinguished from inflammation and instead possess important anti-inflammatory and metabolic properties. In this opinion piece, we suggest that both ROS and myokines are important players in muscle adaptation to exercise....

Implications of Patient Portal Transparency in Oncology: Qualitative Interview Study on the Experiences of Patients, Oncologists, and Medical Informaticists.

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Alpert, Jordan M; Morris, Bonny B; Thomson, Maria D; Matin, Khalid; Brown, Richard F

2018-03-26

Providing patients with unrestricted access to their electronic medical records through patient portals has impacted patient-provider communication and patients' personal health knowledge. However, little is known about how patient portals are used in oncology. The aim of this study was to understand attitudes of the portal's adoption for oncology and to identify the advantages and disadvantages of using the portal to communicate and view medical information. In-depth semistructured interviews were conducted with 60 participants: 35 patients, 13 oncologists, and 12 medical informaticists. Interviews were recorded, transcribed, and thematically analyzed to identify critical incidents and general attitudes encountered by participants. Two primary themes were discovered: (1) implementation practices influence attitudes, in which the decision-making and execution process of introducing portals throughout the hospital did not include the input of oncologists. Lack of oncologists' involvement led to a lack of knowledge about portal functionality, such as not knowing the time period when test results would be disclosed to patients; (2) perceptions of portals as communication tools varies by user type, meaning that each participant group (patients, oncologists, and medical informaticists) had varied opinions about how the portal should be used to transmit and receive information. Oncologists and medical informaticists had difficulty understanding one another's culture and communication processes in their fields, while patients had preferences for how they would like to receive communication, but it largely depended upon the type of test being disclosed. The majority of patients (54%, 19/35) who participated in this study viewed lab results or scan reports via the portal before being contacted by a clinician. Most were relatively comfortable with this manner of disclosure but still preferred face-to-face or telephone communication. Findings from this study indicate that

Endoplasmic Reticulum Stress and Associated ROS

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Hafiz Maher Ali Zeeshan

2016-03-01

Full Text Available The endoplasmic reticulum (ER is a fascinating network of tubules through which secretory and transmembrane proteins enter unfolded and exit as either folded or misfolded proteins, after which they are directed either toward other organelles or to degradation, respectively. The ER redox environment dictates the fate of entering proteins, and the level of redox signaling mediators modulates the level of reactive oxygen species (ROS. Accumulating evidence suggests the interrelation of ER stress and ROS with redox signaling mediators such as protein disulfide isomerase (PDI-endoplasmic reticulum oxidoreductin (ERO-1, glutathione (GSH/glutathione disuphide (GSSG, NADPH oxidase 4 (Nox4, NADPH-P450 reductase (NPR, and calcium. Here, we reviewed persistent ER stress and protein misfolding-initiated ROS cascades and their significant roles in the pathogenesis of multiple human disorders, including neurodegenerative diseases, diabetes mellitus, atherosclerosis, inflammation, ischemia, and kidney and liver diseases.

YARP-ROS Inter-Operation in a 2D Navigation Task

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Marco Randazzo

2018-02-01

Full Text Available This paper presents some recent developments in YARP middleware, aimed to improve its integration with ROS. They include a new mechanism to read/write ROS transform frames and a new set of standard interfaces to intercommunicate with the ROS navigation stack. A novel set of YARP companion modules, which provide basic navigation functionalities for robots unable to run ROS, is also presented. These modules are optional, independent from each other, and they provide compatible functionalities to well-known packages available inside ROS framework. This paper also discusses how developers can customize their own hybrid YARP-ROS environment in the way it best suits their needs (e.g., the system can be configured to have a YARP application sending navigation commands to a ROS path planner, or vice versa. A number of available possibilities is presented through a set of chosen test cases applied to both real and simulated robots. Finally, example applications discussed in this paper are also made available to the community by providing snippets of code and links to source files hosted on github repository https://github.com/robotology.1

Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals.

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Prasad, Sahdeo; Gupta, Subash C; Tyagi, Amit K

2017-02-28

Extensive research over the past half a century indicates that reactive oxygen species (ROS) play an important role in cancer. Although low levels of ROS can be beneficial, excessive accumulation can promote cancer. One characteristic of cancer cells that distinguishes them from normal cells is their ability to produce increased numbers of ROS and their increased dependence on an antioxidant defense system. ROS are produced as a byproduct intracellularly by mitochondria and other cellular elements and exogenously by pollutants, tobacco, smoke, drugs, xenobiotics, and radiation. ROS modulate various cell signaling pathways, which are primarily mediated through the transcription factors NF-κB and STAT3, hypoxia-inducible factor-1α, kinases, growth factors, cytokines and other proteins, and enzymes; these pathways have been linked to cellular transformation, inflammation, tumor survival, proliferation, invasion, angiogenesis, and metastasis of cancer. ROS are also associated with epigenetic changes in genes, which is helpful in diagnosing diseases. This review considers the role of ROS in the various stages of cancer development. Finally, we provide evidence that nutraceuticals derived from Mother Nature are highly effective in eliminating cancer cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prevalence of the burnout syndrome among Brazilian medical oncologists

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João Glasberg

2007-02-01

Full Text Available INTRODUCTION: Burnout syndrome which is prevalent among oncologists is characterized by three aspects: emotional exhaustion, depersonalization and low personal accomplishment. The purpose was to evaluate prevalence of the burnout syndrome among Brazilian medical oncologists and the variables that correlate with its presence. METHODS: A survey was conducted with members of the Brazilian Society of Medical Oncology (SBOC who received three questionnaires (general, Maslach burnout questionnaire and an opinion survey mailed to all 458 members. RESULTS: Response rate was of 22.3%. According to the criteria proposed by Grunfeld, which consider burnout present when at least one of the aspects is severely abnormal, prevalence of this syndrome was 68.6% (95% confidence interval, CI: 58.68% to 77.45%. By multivariate analysis having a hobby/physical activity, a religious affiliation, older age, living with a companion and rating vacation time as sufficient were correlated significantly and independently with burnout syndrome. CONCLUSIONS: The burnout syndrome is prevalent among Brazilian oncologists. Oncologists having sufficient personal and social resources to engage in a hobby, physical activity, have enough vacation time and religious activities are at lower risk of developing burnout.INTRODUÇÃO: A Síndrome da Estafa Profissional (SEP é considerada uma doença caracterizada por três componentes básicos: exaustão emocional (EE, despersonalização (DP e reduzida realização pessoal (RP, sendo identificada em oncologistas. OBJETIVO: Analisar a prevalência da SEP entre oncologistas clínicos e possíveis fatores relacionados. MÉTODOS: Foram enviados três questionários (Questionário Geral, Questionário Maslach de Burnout e Questionário de Opinião para 458 cancerologistas cadastrados na Sociedade Brasileira de Oncologia Clínica (SBOC. RESULTADOS: A taxa de resposta foi de 20%. 43,3% dos entrevistados demonstraram nível baixo de EE, 57

ROS and RNS in plant physiology: an overview.

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Del Río, Luis A

2015-05-01

The production of reactive oxygen species (ROS) is the unavoidable consequence of aerobic life. ROS is a collective term that includes both oxygen radicals, like superoxide (O 2. -) and hydroxyl (·OH) radicals, and other non-radicals such as hydrogen peroxide (H2O2), singlet oxygen ((1)O2 or (1)Δg), etc. In plants, ROS are produced in different cell compartments and are oxidizing species, particularly hydroxyl radicals and singlet oxygen, that can produce serious damage in biological systems (oxidative stress). However, plant cells also have an array of antioxidants which, normally, can scavenge the excess oxidants produced and so avoid deleterious effects on the plant cell bio-molecules. The concept of 'oxidative stress' was re-evaluated in recent years and the term 'oxidative signalling' was created. This means that ROS production, apart from being a potentially harmful process, is also an important component of the signalling network that plants use for their development and for responding to environmental challenges. It is known that ROS play an important role regulating numerous biological processes such as growth, development, response to biotic and environmental stresses, and programmed cell death. The term reactive nitrogen species (RNS) includes radicals like nitric oxide (NO· ) and nitric dioxide (NO2.), as well as non-radicals such as nitrous acid (HNO2) and dinitrogen tetroxide (N2O4), among others. RNS are also produced in plants although the generating systems have still not been fully characterized. Nitric oxide (NO·) has an important function as a key signalling molecule in plant growth, development, and senescence, and RNS, like ROS, also play an important role as signalling molecules in the response to environmental (abiotic) stress. Similarly, NO· is a key mediator, in co-operation with ROS, in the defence response to pathogen attacks in plants. ROS and RNS have been demonstrated to have an increasingly important role in biology and medicine

Heme-induced ROS in Trypanosoma cruzi activates CaMKII-like that triggers epimastigote proliferation. One helpful effect of ROS.

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Natália Pereira de Almeida Nogueira

Full Text Available Heme is a ubiquitous molecule that has a number of physiological roles. The toxic effects of this molecule have been demonstrated in various models, based on both its pro-oxidant nature and through a detergent mechanism. It is estimated that about 10 mM of heme is released during blood digestion in the blood-sucking bug's midgut. The parasite Trypanosoma cruzi, the agent of Chagas' disease, proliferates in the midgut of the insect vector; however, heme metabolism in trypanosomatids remains to be elucidated. Here we provide a mechanistic explanation for the proliferative effects of heme on trypanosomatids. Heme, but not other porphyrins, induced T. cruzi proliferation, and this phenomenon was accompanied by a marked increase in reactive oxygen species (ROS formation in epimastigotes when monitored by ROS-sensitive fluorescent probes. Heme-induced ROS production was time- and concentration-dependent. In addition, lipid peroxidation and the formation of 4-hydroxy-2-nonenal (4-HNE adducts with parasite proteins were increased in epimastigotes in the presence of heme. Conversely, the antioxidants urate and GSH reversed the heme-induced ROS. Urate also decreased parasite proliferation. Among several protein kinase inhibitors tested only specific inhibitors of CaMKII, KN93 and Myr-AIP, were able to abolish heme-induced ROS formation in epimastigotes leading to parasite growth impairment. Taken together, these data provide new insight into T. cruzi- insect vector interactions: heme, a molecule from the blood digestion, triggers epimastigote proliferation through a redox-sensitive signalling mechanism.

Perceptions and practices regarding women's vaginal health following radiation therapy: A survey of radiation oncologists practicing in the United States.

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Kachnic, Lisa A; Bruner, Deborah W; Qureshi, Muhammad M; Russo, Gregory A

Vaginal stenosis (VS) is a recognized complication of pelvic and vaginal radiation therapy (RT). A 26-item survey assessing the signs/symptoms, risk factors, diagnosis, prevention, treatment, and impact of VS on women's sexual health was distributed to radiation oncologists. Descriptive statistics were calculated. Chi-square tests examined differences in categorical responses. A total of 233 (10.5%) participants completed the entire survey. Twelve percent, 21%, and 68% report treating gynecologic (GYN) tumors only, non-GYN pelvic tumors only, or both, respectively. Regarding risk factors, 78% believed that VS can be caused by pelvic RT alone, 91% by vaginal brachytherapy alone, and 98% by combined pelvic RT and vaginal brachytherapy. Approximately one-half of respondents felt that being postmenopausal and having a hysterectomy before radiation therapy were risk factors for VS, whereas the other half felt that these were not risk factors. All respondents agreed that VS is a clinical diagnosis. Respondents indicated that VS symptoms include dyspareunia, vaginal pain, dryness, and/or bleeding (100%, 90%, 85%, and 72%, respectively); 65% indicated all 4. The most commonly recommended treatment for VS is vaginal dilator use. Radiation oncologists who treat GYN-only versus non-GYN cancers were more likely to perform a vaginal examination, to distribute written instructions regarding vaginal dilator use (P = .002), to have vaginal bleeding reported after RT (P = .001), and to refer patients to a sexual counselor (P = .007). Most providers (73%) expressed willingness to participate in prospective research on the diagnosis and treatment of VS. This is the first large-scale survey of radiation oncologists' perceptions and practices regarding VS. There is agreement among providers regarding the signs/symptoms of VS and strategies for its prevention/treatment using vaginal dilators. Further prospective and observational research is needed. This survey shows a willingness on

Middleware Interoperability for Robotics: A ROS-YARP Framework

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Plinio Moreno

2016-10-01

Full Text Available Middlewares are fundamental tools for progress in research and applications in robotics. They enable the integration of multiple heterogeneous sensing and actuation devices, as well as providing general purpose modules for key robotics functions (kinematics, navigation, planning. However, no existing middleware yet provides a complete set of functionalities for all robotics applications, and many robots may need to rely on more than one framework. This paper focuses on the interoperability between two of the most prevalent middleware in robotics: YARP and ROS. Interoperability between middlewares should ideally allow users to execute existing software without the necessity of: (i changing the existing code, and (ii writing hand-coded ``bridges'' for each use-case. We propose a framework enabling the communication between existing YARP modules and ROS nodes for robotics applications in an automated way. Our approach generates the ``bridging gap'' code from a configuration file, connecting YARP ports and ROS topics through code-generated YARP Bottles. %%The configuration file must describe: (i the sender entities, (ii the way to group and convert the information read from the sender, (iii the structure of the output message and (iv the receiving entity. Our choice for the many inputs to one output is the most common use-case in robotics applications, where examples include filtering, decision making and visualization. %We support YARP/ROS and ROS/YARP sender/receiver configurations, which are demonstrated in a humanoid on wheels robot that uses YARP for upper body motor control and visual perception, and ROS for mobile base control and navigation algorithms.

The role of mechanical force and ROS in integrin-dependent signals.

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Kathrin S Zeller

Full Text Available Cells are exposed to several types of integrin stimuli, which generate responses generally referred to as "integrin signals", but the specific responses to different integrin stimuli are poorly defined. In this study, signals induced by integrin ligation during cell attachment, mechanical force from intracellular contraction, or cell stretching by external force were compared. The elevated phosphorylation levels of several proteins during the early phase of cell attachment and spreading of fibroblast cell lines were not affected by inhibition of ROCK and myosin II activity, i.e. the reactions occurred independently of intracellular contractile force acting on the adhesion sites. The contraction-independent phosphorylation sites included ERK1/2 T202/Y204, AKT S473, p130CAS Y410, and cofilin S3. In contrast to cell attachment, cyclic stretching of the adherent cells induced a robust phosphorylation only of ERK1/2 and the phosphorylation levels of the other investigated proteins were not or only moderately affected by stretching. No major differences between signaling via α5β1 or αvβ3 integrins were detected. The importance of mitochondrial ROS for the integrin-induced signaling pathways was investigated using rotenone, a specific inhibitor of complex I in the respiratory chain. While rotenone only moderately reduced ATP levels and hardly affected the signals induced by cyclic cell stretching, it abolished the activation of AKT and reduced the actin polymerization rate in response to attachment in both cell lines. In contrast, scavenging of extracellular ROS with catalase or the vitamin C analog Asc-2P did not significantly influence the attachment-derived signaling, but caused a selective and pronounced enhancement of ERK1/2 phosphorylation in response to stretching. In conclusion, the results showed that "integrin signals" are composed of separate sets of reactions triggered by different types of integrin stimulation. Mitochondrial ROS and

Burnout syndrome in the practice of oncology: results of a random survey of 1,000 oncologists.

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Whippen, D A; Canellos, G P

1991-10-01

Burnout, the end result of stress, can occur in any profession. We set out to determine the extent of burnout among a representative group of American oncologists. A questionnaire with 12 specific points was designed and prepared by the authors. It was mailed to 1,000 randomly selected physician subscribers to the Journal of Clinical Oncology. Five hundred ninety-eight completed surveys (60%) were returned before the cut-off date and included in the analysis. Overall, 56% of the respondents reported experiencing burnout in their professional life. No significance was found between the incidence of burnout and specialty within oncology, year medical training ended, or practice location. Significance was found, however, between type of practice and the incidence of burnout; institution- or university-based oncologists reported a lower incidence of burnout (47%) versus all other types of practice (66% burnout rate for oncology plus internal medicine, 63% for private adult oncology only, 39% for pediatric oncologists [there were too few pediatric oncologists for this rate to be significant], and 64% for others; P = .0003). Frustration or a sense of failure was the most frequently chosen (56%) description of burnout, and insufficient personal and/or vacation time was the most frequent reason (57%) chosen to explain the existence of burnout. To alleviate burnout, the majority (69%) of respondents indicated the need for more vacation or personal time. Administering palliative or terminal care, reimbursement issues, and a heavy work load were identified as contributing factors to burnout. Given the high response to the questionnaire and a 56% incidence of burnout in the surveyed population, it is concluded that further research on this issue is required.

A "miracle" cancer drug in the era of social media: A survey of Brazilian oncologists' opinions and experience with phosphoethanolamine.

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Rêgo, Juliana Florinda M; Lopes, Gilberto; Riechelmann, Rachel P; Sternberg, Cinthya; Ferrari, Claudio; Fernandes, Gustavo

2017-01-01

Patients who are treating cancer have often used alternative therapies. In the internet era, information can be broadcasted widely, and this happened with phosphoethanolamine in Brazil, where this substance was claimed by the population to be the "cure for cancer." This is a cross-sectional study developed by the Brazilian Society of Clinical Oncology (SBOC). An objectively structured questionnaire was sent by e-mail and SMS to active MDs members of the SBOC. Descriptive statistics was used to evaluate the data. Statistical significance between the variables was tested by Pearson's Chi-squared test (p<0.05 was considered significance). The survey was sent to 1,072 oncologists, and 398 (37.1%) answered at least part of it. One hundred and fifteen (28.9%) had followed patients who had used phosphoethanolamine. Among these, 14 (12.2%) observed adverse events and four (3.5%) attributed clinical benefit to the substance. Most of the oncologists (n=331; 83.2%) believe that it should only be used as part of a clinical trial protocol. Most physicians did not recommend this drug to their patients (n=311; 78.1%). Oncologists in Southeast, South and Midwest Brazil were more likely to have patients taking the drug compared to the Northern and Northeastern regions. This is the first survey to assess the opinion and experience of oncologists about this alternative therapy. Most oncologists in Brazil do not believe that synthetic phosphoethanolamine is active in cancer treatment, do not recommend its use without proper evaluation, and state that it should only be available to patients in the context of clinical trials.

Examination of Industry Payments to Radiation Oncologists in 2014 Using the Centers for Medicare and Medicaid Services Open Payments Database

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Jairam, Vikram [Yale School of Medicine, New Haven, Connecticut (United States); Yu, James B., E-mail: james.b.yu@yale.edu [Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut (United States)

2016-01-01

Purpose: To use the Centers for Medicare and Medicaid Services Open Payments database to characterize payments made to radiation oncologists and compare their payment profile with that of medical and surgical oncologists. Methods and Materials: The June 2015 release of the Open Payments database was accessed, containing all payments made to physicians in 2014. The general payments dataset was used for analysis. Data on payments made to medical, surgical, and radiation oncologists was obtained and compared. Within radiation oncology, data regarding payment category, sponsorship, and geographic distribution were identified. Basic statistics including mean, median, range, and sum were calculated by provider and by transaction. Results: Among the 3 oncologic specialties, radiation oncology had the smallest proportion (58%) of compensated physicians and the lowest mean ($1620) and median ($112) payment per provider. Surgical oncology had the highest proportion (84%) of compensated physicians, whereas medical oncology had the highest mean ($6371) and median ($448) payment per physician. Within radiation oncology, nonconsulting services accounted for the most money to physicians ($1,042,556), whereas the majority of the sponsors were medical device companies (52%). Radiation oncologists in the West accepted the most money ($2,041,603) of any US Census region. Conclusions: Radiation oncologists in 2014 received a large number of payments from industry, although less than their medical or surgical counterparts. As the Open Payments database continues to be improved, it remains to be seen whether this information will be used by patients to inform choice of providers or by lawmakers to enact policy regulating physician–industry relationships.

Effect of a Patient-Centered Communication Intervention on Oncologist-Patient Communication, Quality of Life, and Health Care Utilization in Advanced Cancer

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Epstein, Ronald M.; Duberstein, Paul R.; Fenton, Joshua J.; Fiscella, Kevin; Hoerger, Michael; Tancredi, Daniel J.; Xing, Guibo; Gramling, Robert; Mohile, Supriya; Franks, Peter; Kaesberg, Paul; Plumb, Sandy; Cipri, Camille S.; Street, Richard L.; Shields, Cleveland G.; Back, Anthony L.; Butow, Phyllis; Walczak, Adam; Tattersall, Martin; Venuti, Alison; Sullivan, Peter; Robinson, Mark; Hoh, Beth; Lewis, Linda; Kravitz, Richard L.

2018-01-01

IMPORTANCE Observational studies demonstrate links between patient-centered communication, quality of life (QOL), and aggressive treatments in advanced cancer, yet few randomized clinical trials (RCTs) of communication interventions have been reported. OBJECTIVE To determine whether a combined intervention involving oncologists, patients with advanced cancer, and caregivers would promote patient-centered communication, and to estimate intervention effects on shared understanding, patient-physician relationships, QOL, and aggressive treatments in the last 30 days of life. DESIGN, SETTING, AND PARTICIPANTS Cluster RCT at community- and hospital-based cancer clinics in Western New York and Northern California; 38 medical oncologists (mean age 44.6 years; 11 (29%) female) and 265 community-dwelling adult patients with advanced nonhematologic cancer participated (mean age, 64.4 years, 146 [55.0%] female, 235 [89%] white; enrolled August 2012 to June 2014; followed for 3 years); 194 patients had participating caregivers. INTERVENTIONS Oncologists received individualized communication training using standardized patient instructors while patients received question prompt lists and individualized communication coaching to identify issues to address during an upcoming oncologist visit. Both interventions focused on engaging patients in consultations, responding to emotions, informing patients about prognosis and treatment choices, and balanced framing of information. Control participants received no training. MAIN OUTCOMES AND MEASURES The prespecified primary outcome was a composite measure of patient-centered communication coded from audio recordings of the first oncologist visit following patient coaching (intervention group) or enrollment (control). Secondary outcomes included the patient-physician relationship, shared understanding of prognosis, QOL, and aggressive treatments and hospice use in the last 30 days of life. RESULTS Data from 38 oncologists (19 randomized

Practice Patterns, Attitudes, and Barriers to Palliative Care Consultation by Gynecologic Oncologists.

Science.gov (United States)

Buckley de Meritens, Alexandre; Margolis, Benjamin; Blinderman, Craig; Prigerson, Holly G; Maciejewski, Paul K; Shen, Megan J; Hou, June Y; Burke, William M; Wright, Jason D; Tergas, Ana I

2017-09-01

We sought to describe practice patterns, attitudes, and barriers to the integration of palliative care services by gynecologic oncologists. Members of the Society of Gynecologic Oncology were electronically surveyed regarding their practice of incorporating palliative care services and to identify barriers for consultation. Descriptive statistics were used, and two-sample z-tests of proportions were performed to compare responses to related questions. Of the 145 respondents, 71% were attending physicians and 58% worked at an academic medical center. The vast majority (92%) had palliative care services available for consultation at their hospital; 48% thought that palliative care services were appropriately used, 51% thought they were underused, and 1% thought they were overused. Thirty percent of respondents thought that palliative care services should be incorporated at first recurrence, whereas 42% thought palliative care should be incorporated when prognosis for life expectancy is ≤ 6 months. Most participants (75%) responded that palliative care consultation is reasonable for symptom control at any stage of disease. Respondents were most likely to consult palliative care services for pain control (53%) and other symptoms (63%). Eighty-three percent of respondents thought that communicating prognosis is the primary team's responsibility, whereas the responsibilities for pain and symptom control, resuscitation status, and goals of care discussions were split between the primary team only and both teams. The main barrier for consulting palliative care services was the concern that patients and families would feel abandoned by the primary oncologist (73%). Ninety-seven percent of respondents answered that palliative care services are useful to improve patient care. The majority of gynecologic oncologists perceived palliative care as a useful collaboration that is underused. Fear of perceived abandonment by the patient and family members was identified as a

Correlates of oncologist-issued referrals for psycho-oncology services: what we learned from the electronic voluntary screening and referral system for depression (eVSRS-D).

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Lee, Joo-Young; Jung, Dooyoung; Kim, Won-Hyoung; Lee, Hyuk-Joon; Noh, Dong-Young; Hahm, Bong-Jin

2016-02-01

Depression in cancer patients is under-recognized and under-treated. To better identify depression, we designed a voluntary depression screening system. Based on its data, we examined trends in oncologist-issued referrals for the psycho-oncology service (POS). The Electronic Voluntary Screening and Referral System for Depression (eVSRS-D) comprises self-screening, automated reporting, and referral guidance. Using touch-screen kiosks at a tertiary hospital in Korea, participants with cancer completed the Patient Health Questionnaire-9 at their convenience, received the results, and reported their willingness to participate in POS. At oncology appointments, oncologists received the screening reports and issued referrals following pre-recommended guidelines. The correlates of actual referrals were examined across all participants and within the willing and non-willing groups. Among the 838 participants, 56.3% reported severe depression symptoms, 30.5% wanted a referral, and 14.8% were actually referred. The correlates of participants' desire for referral were more severe depression symptoms, being unmarried, and being metastasis and recurrence free. Among all participants, the correlates of actual referrals were unemployment, less severe depression symptoms, poorer performance, treatment status, and wanting a referral. The sole correlate of actual referrals within the non-willing group was poorer performance, and no significant correlates existed within the willing group. The non-referrals were mostly (87.1%) because of postponed decisions. The eVSRS-D cannot definitively diagnose major depression but may efficiently self-select a population with significant depression symptoms. The patients' willingness to engage the POS most strongly predicted the actual referrals. Oncologist reviews of screening reports may not result in further depression severity-specific referrals. Copyright © 2015 John Wiley & Sons, Ltd.

Patient and oncologist perceptions regarding symptoms and impact on quality-of-life of oral mucositis in cancer treatment: results from the Awareness Drives Oral Mucositis PercepTion (ADOPT) study.

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Kanagalingam, Jeevendra; Wahid, Mohamed Ibrahim A; Lin, Jin-Ching; Cupino, Nonette A; Liu, Edward; Kang, Jin-Hyoung; Bazarbashi, Shouki; Bender Moreira, Nicole; Arumugam, Harsha; Mueller, Stefan; Moon, Hanlim

2018-07-01

This descriptive cross-sectional survey aims to assess the level of concordance between the perspectives of oncologists and those of patients regarding oral mucositis (OM) symptoms, and the impact of OM on various aspects of daily living and concurrent cancer management. Oncologists involved in OM management (n = 105), and patients who developed OM during cancer treatment (n = 175), were recruited from seven Asian countries. Oncologists completed a face-to-face, quantitative interview; patients completed a face-to-face interview, and a self-reported questionnaire. Oncologists and patients ranked treatment-induced OM among the three most important toxicities of cancer therapy requiring intervention. The most frequent OM symptoms reported by patients were oral ulcers (74%), dry mouth (73%), and difficulty swallowing (62%). Oncologists expected mild OM symptoms to last slightly longer than 1 week, whereas patients reported mild symptoms for more than 2 weeks. In mild-to-moderate OM, oncologists underestimated patients' pain experience. Overall, only 45% of oncologists said they would initiate OM prophylaxis when cancer therapy started. Of the 87% of patients who said they used their prescribed medications, only 16% reported using prophylactically prescribed medication. While oncologists' concerns related to the delays and interruptions of cancer treatment, patients tended to focus on the effects of OM on eating, drinking, and talking. Oncologists' and patients' perceptions about treatment-induced OM differ. To overcome discordant perspectives, there is a need to raise general awareness and improve proactive management of OM. As noted in recent guidelines, supportive cancer care is critical for ensuring optimal therapy and for improving the patient's experience.

Calcium and ROS: A mutual interplay

Science.gov (United States)

Görlach, Agnes; Bertram, Katharina; Hudecova, Sona; Krizanova, Olga

2015-01-01

Calcium is an important second messenger involved in intra- and extracellular signaling cascades and plays an essential role in cell life and death decisions. The Ca2+ signaling network works in many different ways to regulate cellular processes that function over a wide dynamic range due to the action of buffers, pumps and exchangers on the plasma membrane as well as in internal stores. Calcium signaling pathways interact with other cellular signaling systems such as reactive oxygen species (ROS). Although initially considered to be potentially detrimental byproducts of aerobic metabolism, it is now clear that ROS generated in sub-toxic levels by different intracellular systems act as signaling molecules involved in various cellular processes including growth and cell death. Increasing evidence suggests a mutual interplay between calcium and ROS signaling systems which seems to have important implications for fine tuning cellular signaling networks. However, dysfunction in either of the systems might affect the other system thus potentiating harmful effects which might contribute to the pathogenesis of various disorders. PMID:26296072

Adjuvant chemotherapy in node negative breast cancer: patterns of use and oncologists' preferences

NARCIS (Netherlands)

Stiggelbout, A. M.; de Haes, J. C.; van de Velde, C. J.

2000-01-01

BACKGROUND: A worldwide variation in policy is seen regarding adjuvant systemic treatment for node negative breast cancer (NNBC). After the first presentations of the 10-year EBCTCG results, a study was carried out in the Netherlands to assess patterns of care and to obtain the views of oncologists

Detection of ROS Induced Proteomic Signatures by Mass Spectrometry

Directory of Open Access Journals (Sweden)

Brian McDonagh

2017-07-01

Full Text Available Reversible and irreversible post-translational modifications (PTMs induced by endogenously generated reactive oxygen species (ROS in regulatory enzymes and proteins plays an essential role in cellular signaling. Almost all cellular processes including metabolism, transcription, translation and degradation have been identified as containing redox regulated proteins. Specific redox modifications of key amino acids generated by ROS offers a dynamic and versatile means to rapidly alter the activity or functional structure of proteins in response to biochemical, environmental, genetic and pathological perturbations. How the proteome responds to these stimuli is of critical importance in oxidant physiology, as it can regulate the cell stress response by reversible and irreversible PTMs, affecting protein activity and protein-protein interactions. Due to the highly labile nature of many ROS species, applying redox proteomics can provide a signature footprint of the ROS species generated. Ideally redox proteomic approaches would allow; (1 the identification of the specific PTM, (2 identification of the amino acid residue that is modified and (3 the percentage of the protein containing the PTM. New developments in MS offer the opportunity of a more sensitive targeted proteomic approach and retrospective data analysis. Subsequent bioinformatics analysis can provide an insight into the biochemical and physiological pathways or cell signaling cascades that are affected by ROS generation. This mini-review will detail current redox proteomic approaches to identify and quantify ROS induced PTMs and the subsequent effects on cellular signaling.

ROS inhibitor N-acetyl-L-cysteine antagonizes the activity of proteasome inhibitors.

Science.gov (United States)

Halasi, Marianna; Wang, Ming; Chavan, Tanmay S; Gaponenko, Vadim; Hay, Nissim; Gartel, Andrei L

2013-09-01

NAC (N-acetyl-L-cysteine) is commonly used to identify and test ROS (reactive oxygen species) inducers, and to inhibit ROS. In the present study, we identified inhibition of proteasome inhibitors as a novel activity of NAC. Both NAC and catalase, another known scavenger of ROS, similarly inhibited ROS levels and apoptosis associated with H₂O₂. However, only NAC, and not catalase or another ROS scavenger Trolox, was able to prevent effects linked to proteasome inhibition, such as protein stabilization, apoptosis and accumulation of ubiquitin conjugates. These observations suggest that NAC has a dual activity as an inhibitor of ROS and proteasome inhibitors. Recently, NAC was used as a ROS inhibitor to functionally characterize a novel anticancer compound, piperlongumine, leading to its description as a ROS inducer. In contrast, our own experiments showed that this compound depicts features of proteasome inhibitors including suppression of FOXM1 (Forkhead box protein M1), stabilization of cellular proteins, induction of ROS-independent apoptosis and enhanced accumulation of ubiquitin conjugates. In addition, NAC, but not catalase or Trolox, interfered with the activity of piperlongumine, further supporting that piperlongumine is a proteasome inhibitor. Most importantly, we showed that NAC, but not other ROS scavengers, directly binds to proteasome inhibitors. To our knowledge, NAC is the first known compound that directly interacts with and antagonizes the activity of proteasome inhibitors. Taken together, the findings of the present study suggest that, as a result of the dual nature of NAC, data interpretation might not be straightforward when NAC is utilized as an antioxidant to demonstrate ROS involvement in drug-induced apoptosis.

Expert Radiation Oncologist Interpretations of Involved-Site Radiation Therapy Guidelines in the Management of Hodgkin Lymphoma

Energy Technology Data Exchange (ETDEWEB)

Hoppe, Bradford S. [University of Florida Health Proton Therapy Institute, Jacksonville, Florida (United States); Hoppe, Richard T., E-mail: rhoppe@stanford.edu [Stanford Cancer Institute, Stanford, California (United States)

2015-05-01

Purpose: Recently, involved-site radiation therapy (ISRT) guidelines have been developed and published to replace the previous concept of involved-field radiation therapy for patients with lymphoma. However, these ISRT guidelines may be interpreted in different ways, posing difficulties for prospective clinical trials. This study reports survey results regarding interpretation of the ISRT guidelines. Methods and Materials: Forty-four expert lymphoma radiation oncologists were asked to participate in a survey that included 7 different cases associated with 9 questions. The questions pertained to ISRT contouring and asked respondents to choose between 2 different answers (no “correct” answer) and a third write-in option allowed. Results: Fifty-two percent of those surveyed responded to the questionnaire. Among those who responded, 72% have practiced for >10 years, 46% have treated >20 Hodgkin lymphoma cases annually, and 100% were familiar with the ISRT concept. Among the 9 questions associated with the 7 cases, 3 had concordance among the expert radiation oncologists of greater than 70%. Six of the questions had less than 70% concordance (range, 56%-67%). Conclusions: Even among expert radiation oncologists, interpretation of ISRT guidelines is variable. Further guidance for ISRT field design will be needed to reduce variability among practicing physicians.

Burnout among psychosocial oncologists in Israel: The direct and indirect effects of job demands and job resources.

Science.gov (United States)

Shinan-Altman, Shiri; Cohen, Miri; Rasmussen, Victoria; Turnell, Adrienne; Butow, Phyllis

2017-12-19

Psychosocial oncologists may be particularly vulnerable to burnout. This study aimed to assess burnout among Israeli psychosocial oncologists in relation to the Job Demands-Resources model and the coping strategies model. Participants included 85 of 128 listed psychosocial oncologists currently working with cancer patients. They completed a questionnaire assessing emotional exhaustion, depersonalization, job demands, job resources, work engagement, overcommitment, and perceived value of work. The mean level of burnout was low, whereas 16.3% experienced high levels of emotional exhaustion and only 2.4% experienced high levels of depersonalization. According to mediation analysis, overcommitment, partially mediated job demands-burnout associations, and work engagement mediated the perceived value-burnout association. Job resources and burnout were not related, either directly or indirectly. Significance of results The study extended the Job Demands-Resources model to include perceived value as an additional resource, and work-engagement and overcommitment as coping strategies. Two distinct patterns of associations were found between work characteristics and burnout: the positive-protective pattern (perceived value and work engagement) and the negative pattern (job demands and overcommitment). These two patterns should be considered for further research and for implementing preventive interventions to reduce burnout in the workplace setting.

Towards Interactive, Incremental Programming of ROS Nodes

DEFF Research Database (Denmark)

Adam, Marian Sorin; Schultz, Ulrik Pagh

Writing software for controlling robots is a complex task, usually demanding command of many programming languages and requiring significant experimentation. We believe that a bottom-up development process that complements traditional component- and MDSD-based approaches can facilitate...... experimentation. We propose the use of an internal DSL providing both a tool to interactively create ROS nodes and a behaviour-replacement mechanism to interactively reshape existing ROS nodes by wrapping the external interfaces (the publish/subscribe topics), dynamically controlled using the Python command line...

MAP17, a ROS-dependent oncogene

International Nuclear Information System (INIS)

Carnero, Amancio

2012-01-01

MAP17 is a small 17 kDa non-glycosylated membrane protein previously identified as being overexpressed in carcinomas. Breast tumor cells that overexpress MAP17 show an increased tumoral phenotype with enhanced proliferative capabilities both in the presence or the absence of contact inhibition, decreased apoptotic sensitivity, and increased migration. MAP17-expressing clones also grow better in nude mice. The increased malignant cell behavior induced by MAP17 is associated with an increase in reactive oxygen species (ROS) production, and the treatment of MAP17-expressing cells with antioxidants results in a reduction in the tumorigenic properties of these cells. The MAP17-dependent increase in ROS and tumorigenesis relies on its PDZ-binding domain because disruption of this sequence by point mutations abolishes the ability of MAP17 to enhance ROS production and tumorigenesis. MAP17 is overexpressed in a great variety of human carcinomas, including breast tumors. Immunohistochemical analysis of MAP17 during cancer progression demonstrates that overexpression of the protein strongly correlates with tumoral progression. Generalized MAP17 overexpression in human carcinomas indicates that MAP17 can be a good marker for tumorigenesis and, especially, for malignant progression.

Questionnaire survey to assess the pattern and characteristics of cell-phone usage among Indian oncologists

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Anusheel Munshi

2016-01-01

Conclusion: The results of the first such questionnaire based study have been presented. Most oncologists consider cell-phones a useful tool in patient care. More RO are aware of potential cell-phone hazards compared to non-RO's.

Pediatric oncologists' attitudes towards involving adolescents in decision-making concerning research participation.

Science.gov (United States)

de Vries, Martine C; Wit, Jan M; Engberts, Dirk P; Kaspers, Gertjan J L; van Leeuwen, Evert

2010-07-15

Various regulations and guidelines stipulate the importance of involving adolescents in decision-making concerning research participation. Several studies have shown that in the context of pediatric oncology this involvement is difficult to achieve due to emotional stress, the complexity of research protocols and limited time. Still, up to 80% of adolescents with cancer enter onto a trial during their illness. The aim of this study was to determine clinicians' views and attitudes towards enrolling adolescents in research, considering the difficulties surrounding their involvement in decision-making. A qualitative multicenter study was performed, using in-depth semi-structured interviews on the informed consent process with 15 pediatric hemato-oncologists. Four central themes emerged that characterize clinicians' attitudes towards involving adolescents in the decision-making process: (1) clinicians regard most adolescents as not capable of participating meaningfully in discussions regarding research; (2) clinicians do not always provide adolescents with all information; (3) proxy consent from parents is obtained and is deemed sufficient; (4) clinician-investigator integrity: clinicians judge research protocols as not being harmful and even in the best interest of the adolescent. Clinicians justify not involving adolescents in research discussions by referring to best interest arguments (adolescents' incompetence, proxy consent, and investigator integrity), although this is not in line with legal regulations and ethical guidelines.

Oncologist burnout and compassion fatigue: investigating time pressure at work as a predictor and the mediating role of work-family conflict.

Science.gov (United States)

Kleiner, Sibyl; Wallace, Jean E

2017-09-11

Oncologists are at high risk of poor mental health. Prior research has focused on burnout, and has identified heavy workload as a key predictor. Compassion fatigue among physicians has generally received less attention, although medical specialties such as oncology may be especially at risk of compassion fatigue. We contribute to research by identifying predictors of both burnout and compassion fatigue among oncologists. In doing so, we distinguish between quantitative workload (e.g., work hours) and subjective work pressure, and test whether work-family conflict mediates the relationships between work pressure and burnout or compassion fatigue. In a cross-sectional study, oncologists from across Canada (n = 312) completed questionnaires assessing burnout, compassion fatigue, workload, time pressure at work, work-family conflict, and other personal, family, and occupational characteristics. Analyses use Ordinary Least Squares regression. Subjective time pressure at work is a key predictor of both burnout and compassion fatigue. Our results also show that work-family conflict fully mediates these relationships. Overall, the models explain more of the variation in burnout as compared to compassion fatigue. Our study highlights the need to consider oncologists' subjective time pressure, in addition to quantitative workload, in interventions to improve mental health. The findings also highlight a need to better understand additional predictors of compassion fatigue.

Managing a national radiation oncologist workforce: A workforce planning model

International Nuclear Information System (INIS)

Stuckless, Teri; Milosevic, Michael; Metz, Catherine de; Parliament, Matthew; Tompkins, Brent; Brundage, Michael

2012-01-01

Purpose: The specialty of radiation oncology has experienced significant workforce planning challenges in many countries. Our purpose was to develop and validate a workforce-planning model that would forecast the balance between supply of, and demand for, radiation oncologists in Canada over a minimum 10-year time frame, to identify the model parameters that most influenced this balance, and to suggest how this model may be applicable to other countries. Methods: A forward calculation model was created and populated with data obtained from national sources. Validation was confirmed using a historical prospective approach. Results: Under baseline assumptions, the model predicts a short-term surplus of RO trainees followed by a projected deficit in 2020. Sensitivity analyses showed that access to radiotherapy (proportion of incident cases referred), individual RO workload, average age of retirement and resident training intake most influenced balance of supply and demand. Within plausible ranges of these parameters, substantial shortages or excess of graduates is possible, underscoring the need for ongoing monitoring. Conclusions: Workforce planning in radiation oncology is possible using a projection calculation model based on current system characteristics and modifiable parameters that influence projections. The workload projections should inform policy decision making regarding growth of the specialty and training program resident intake required to meet oncology health services needs. The methods used are applicable to workforce planning for radiation oncology in other countries and for other comparable medical specialties.

Under fungal attack on a metalliferous soil: ROS or not ROS? Insights from Silene paradoxa L. growing under copper stress

International Nuclear Information System (INIS)

Taiti, Cosimo; Giorni, Elisabetta; Colzi, Ilaria; Pignattelli, Sara; Bazihizina, Nadia; Buccianti, Antonella; Luti, Simone; Pazzagli, Luigia; Mancuso, Stefano; Gonnelli, Cristina

2016-01-01

We investigated how the adaptation to metalliferous environments can influence the plant response to biotic stress. In a metallicolous and a non-metallicolous population of Silene paradoxa the induction of oxidative stress and the production of callose and volatiles were evaluated in the presence of copper and of the PAMP fungal protein cerato-platanin, separately and in combination. Our results showed incompatibility between the ordinary ROS-mediated response to fungal attack and the acquired mechanisms of preventing oxidative stress in the tolerant population. A similar situation was also demonstrated by the sensitive population growing in the presence of copper but, in this case, with a lack of certain responses, such as callose production. In addition, in terms of the joint behaviour of emitted volatiles, multivariate statistics showed that not only did the populations respond differently to the presence of copper or biotic stress, but also that the biotic and abiotic stresses interacted in different ways in the two populations. Our results demonstrated that the same incompatibility of hyperaccumulators in ROS-mediated biotic stress signals also seemed to be exhibited by the excluder metallophyte, but without the advantage of being able to rely on the elemental defence for plant protection from natural enemies. - Highlights: • Silene paradoxa plants from metalliferous and nonmetalliferous soil were studied. • Plants were exposed to Cerato-platanin in presence/absence of Cu in culture media. • ROS response was fully present in nonmetallicolous plants only in the absence of Cu. • Similar ROS response in metallicolous plants with or without Cu. - The adaptation to high concentrations of copper was found to interfere with the ordinary ROS-mediated response to fungal attack in an excluder metallophyte.

Career opportunities and benefits for young oncologists in the European Society for Medical Oncology (ESMO)

DEFF Research Database (Denmark)

Morgan, Gilberto; Lambertini, Matteo; Kourie, Hampig Raphael

2016-01-01

The European Society for Medical Oncology (ESMO) is one of the leading societies of oncology professionals in the world. Approximately 30% of the 13 000 ESMO members are below the age of 40 and thus meet the society's definition of young oncologists (YOs). ESMO has identified the training...... and development of YOs as a priority and has therefore established a comprehensive career development programme. This includes a leadership development programme to help identify and develop the future leaders in oncology. Well-trained and highly motivated future generations of multidisciplinary oncologists...... are essential to ensure the optimal evolution of the field of oncology with the ultimate goal of providing the best possible care to patients with cancer. ESMO's career development portfolio is managed and continuously optimised by several dedicated committees composed of ESMO officers and is directly...

Ionized gas (plasma) delivery of reactive oxygen species (ROS) into artificial cells

International Nuclear Information System (INIS)

Hong, Sung-Ha; Jenkins, A Toby A; Szili, Endre J; Short, Robert D

2014-01-01

This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine. (fast track communication)

Ionized gas (plasma) delivery of reactive oxygen species (ROS) into artificial cells

Science.gov (United States)

Hong, Sung-Ha; Szili, Endre J.; Jenkins, A. Toby A.; Short, Robert D.

2014-09-01

This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine.

ROS and trehalose regulate sclerotial development in Rhizoctonia solani AG-1 IA.

Science.gov (United States)

Wang, Chenjiaozi; Pi, Lei; Jiang, Shaofeng; Yang, Mei; Shu, Canwei; Zhou, Erxun

2018-05-01

Rhizoctonia solani AG-1 IA is the causal agent of rice sheath blight (RSB) and causes severe economic losses in rice-growing regions around the world. The sclerotia play an important role in the disease cycle of RSB. In this study, we report the effects of reactive oxygen species (ROS) and trehalose on the sclerotial development of R. solani AG-1 IA. Correlation was found between the level of ROS in R. solani AG-1 IA and sclerotial development. Moreover, we have shown the change of ROS-related enzymatic activities and oxidative burst occurs at the sclerotial initial stage. Six genes related to the ROS scavenging system were quantified in different sclerotial development stages by using quantitative RT-PCR technique, thereby confirming differential gene expression. Fluorescence microscopy analysis of ROS content in mycelia revealed that ROS were predominantly produced at the hyphal branches during the sclerotial initial stage. Furthermore, exogenous trehalose had a significant inhibitory effect on the activities of ROS-related enzymes and oxidative burst and led to a reduction in sclerotial dry weight. Taken together, the findings suggest that ROS has a promoting effect on the development of sclerotia, whereas trehalose serves as an inhibiting factor to sclerotial development in R. solani AG-1 IA. Copyright © 2018 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Survey of tyrosine kinase signaling reveals ROS kinase fusions in human cholangiocarcinoma.

Directory of Open Access Journals (Sweden)

Ting-Lei Gu

Full Text Available Cholangiocarcinoma, also known as bile duct cancer, is the second most common primary hepatic carcinoma with a median survival of less than 2 years. The molecular mechanisms underlying the development of this disease are not clear. To survey activated tyrosine kinases signaling in cholangiocarcinoma, we employed immunoaffinity profiling coupled to mass spectrometry and identified DDR1, EPHA2, EGFR, and ROS tyrosine kinases, along with over 1,000 tyrosine phosphorylation sites from about 750 different proteins in primary cholangiocarcinoma patients. Furthermore, we confirmed the presence of ROS kinase fusions in 8.7% (2 out of 23 of cholangiocarcinoma patients. Expression of the ROS fusions in 3T3 cells confers transforming ability both in vitro and in vivo, and is responsive to its kinase inhibitor. Our data demonstrate that ROS kinase is a promising candidate for a therapeutic target and for a diagnostic molecular marker in cholangiocarcinoma. The identification of ROS tyrosine kinase fusions in cholangiocarcinoma, along with the presence of other ROS kinase fusions in lung cancer and glioblastoma, suggests that a more broadly based screen for activated ROS kinase in cancer is warranted.

Attitudes of medical oncologists in Qatar toward palliative care.

Science.gov (United States)

Zeinah, Ghaith F Abu; Al-Kindi, Sadeer G; Hassan, Azza Adel

2013-09-01

The first and only palliative care (PC) unit in Qatar was established in 2008 to serve adult patients with cancer. As PC was only recently introduced to oncology practice in Qatar and the region, raising awareness among physicians is crucial. This survey study is designed to outline the level of awareness and knowledge of oncologists in Qatar toward PC. In this cross-sectional survey study, copies of a self-constructed questionnaire were distributed to 49 physicians at the National Center for Cancer Care and Research in Qatar during January 2012 and collected for data analysis. The physician response rate was 100%. Less than half of the responders (36.7%) had official training in PC, but the majority (89.8%) showed interest in the field. Only 57.8% of the physicians reported self-competence in providing good PC to the dying patient. On the other hand, up to 69.4% are aware of the guidelines for pain relief and 58.7% apply them in their clinical practice. The concept of PC hospice was familiar to 77.1% of participants. On one hand, 85.7% of the physicians advocated that every medical center should have PC service, while up to 70.8% preferred that patients with short survival expectancy die in the community, rather than in a hospital setting. There is relatively good awareness and knowledge among health care providers specialized in cancer treatment in our hospital, despite the lack of formal training. Further training and informative sessions are required to raise awareness among oncologists and encourage utilization of PC services and thus optimize patient accessibility to PC.

Communication Challenges of Oncologists and Intensivists Caring for Pediatric Oncology Patients: A Qualitative Study.

Science.gov (United States)

Odeniyi, Folasade; Nathanson, Pamela G; Schall, Theodore E; Walter, Jennifer K

2017-12-01

The families of oncology patients requiring intensive care often face increasing complexity in communication with their providers, particularly when patients are cared for by providers from different disciplines. The objective of this study was to describe experiences and challenges faced by pediatric oncologists and intensivists and how the oncologist-intensivist relationship impacts communication and initiation of goals of care discussions (GCDs). We conducted semi-structured interviews with a convenience sample of 10 physicians, including pediatric oncology and intensive care attendings and fellows. We identified key themes (three barriers and four facilitators) to having GCDs with families of oncology patients who have received intensive care. Barriers included challenges to communication within teams because of hierarchy and between teams due to incomplete sharing of information and confusion about who should initiate GCDs; provider experiences of internal conflict about how to engage parents in decision-making and about the "right thing to do" for patients; and lack of education and training in communication. Facilitators included team preparation for family meetings; skills for partnering with families; the presence of palliative care specialists; and informal education in communication and willingness for further training in communication. Notably, the education theme was identified as both a barrier and resource. We identified barriers to communication with families both within and between teams and for individual physicians. Formal communication training and processes that standardize communication to ensure completeness and role delineation between clinical teams may improve oncologists' and intensivists' ability to initiate GCDs, thereby fulfilling their ethical obligations of decision support. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Protective effects of andrographolide analogue AL-1 on ROS-induced RIN-mβ cell death by inducing ROS generation.

Directory of Open Access Journals (Sweden)

Guang-Rong Yan

Full Text Available Oxidative stress is considered to be a major factor contributing to pathogenesis and progression of many diseases. A novel andrographolide-lipoic acid conjugate (AL-1 could protect pancreatic β-cells from reactive oxygen species (ROS-induced oxidative injury. However, its protective mechanism is still unclear. In this work, we used proteomics to identify AL-1-regulated proteins in β-cells and found that 13 of the 71 proteins regulated by AL-1 were closely associated with antioxidation. These differential proteins were mainly involved in the ERK1/2 and AKT1 signaling pathways. Functional investigation demonstrated that AL-1 exerted its protective effects on H2O2-induced cell death of β-cells by generating NADPH oxidase-dependent ROS to activate ERK1/2 and AKT1 signaling pathways. As a consequence, the expressions of antioxidant proteins including Trx1, Prx1 and Prx5, and anti-apoptotic proteins including PDCD6IP, prohibitin, galectin-1 and HSP were upregulated. AL-1 probably worked as a "vaccinum" to activate the cellular antioxidant system by inducing the generation of low concentration ROS which then reciprocally protected β-cells from oxidative damage caused by high-level ROS from H2O2. To the best of our knowledge, this is the first comprehensive proteomic analysis illustrating a novel molecular mechanism for the protective effects of antioxidants on β-cells from H2O2-induced cell death.

Chemotherapy treatment decision-making experiences of older adults with cancer, their family members, oncologists and family physicians: a mixed methods study.

Science.gov (United States)

Puts, Martine T E; Sattar, Schroder; McWatters, Kara; Lee, Katherine; Kulik, Michael; MacDonald, Mary-Ellen; Jang, Raymond; Amir, Eitan; Krzyzanowska, Monika K; Leighl, Natasha; Fitch, Margaret; Joshua, Anthony M; Warde, Padraig; Tourangeau, Ann E; Alibhai, Shabbir M H

2017-03-01

Although comorbidities, frailty, and functional impairment are common in older adults (OA) with cancer, little is known about how these factors are considered during the treatment decision-making process by OAs, their families, and health care providers. Our aim was to better understand the treatment decision process from all these perspectives. A mixed methods multi-perspective longitudinal study using semi-structured interviews and surveys with 29 OAs aged ≥70 years with advanced prostate, breast, colorectal, or lung cancer, 24 of their family members,13 oncologists, and 15 family physicians was conducted. The sample was stratified on age (70-79 and 80+). All interviews were analyzed using thematic analysis. There was no difference in the treatment decision-making experience based on age. Most OAs felt that they should have the final say in the treatment decision, but strongly valued their oncologists' opinion. "Trust in my oncologist" and "chemotherapy as the last resort to prolong life" were the most important reasons to accept treatment. Families indicated a need to improve communication between them, the patient and the specialist, particularly around goals of treatment. Comorbidity and potential side-effects did not play a major role in the treatment decision-making for patients, families, or oncologists. Family physicians reported no involvement in decisions but desired to be more involved. This first study using multiple perspectives showed neither frailty nor comorbidity played a role in the treatment decision-making process. Efforts to improve communication were identified as an opportunity that may enhance quality of care. In a mixed methods study multiple perspective study with older adults with cancer, their family members, their oncologist and their family physician we explored the treatment decision making process and found that most older adults were satisfied with their decision. Comorbidity, functional status and frailty did not impact the

The interplay between autophagy and ROS in tumorigenesis

Energy Technology Data Exchange (ETDEWEB)

Kongara, Sameera [Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ (United States); The Cancer Institute of New Jersey, New Brunswick, NJ (United States); Karantza, Vassiliki, E-mail: karantva@umdnj.edu [Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ (United States); The Cancer Institute of New Jersey, New Brunswick, NJ (United States); Division of Medical Oncology, Department of Internal Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ (United States)

2012-11-21

Reactive oxygen species (ROS) at physiological levels are important cell signaling molecules. However, aberrantly high ROS are intimately associated with disease and commonly observed in cancer. Mitochondria are primary sources of intracellular ROS, and their maintenance is essential to cellular health. Autophagy, an evolutionarily conserved process whereby cytoplasmic components are delivered to lysosomes for degradation, is responsible for mitochondrial turnover and removal of damaged mitochondria. Impaired autophagy is implicated in many pathological conditions, including neurological disorders, inflammatory bowel disease, diabetes, aging, and cancer. The first reports connecting autophagy to cancer showed that allelic loss of the essential autophagy gene BECLIN1 (BECN1) is prevalent in human breast, ovarian, and prostate cancers and that Becn1{sup +/-} mice develop mammary gland hyperplasias, lymphomas, lung and liver tumors. Subsequent studies demonstrated that Atg5{sup -/-} and Atg7{sup -/-} livers give rise to adenomas, Atg4C{sup -/-} mice are susceptible to chemical carcinogenesis, and Bif1{sup -/-} mice are prone to spontaneous tumors, indicating that autophagy defects promote tumorigenesis. Due to defective mitophagy, autophagy-deficient cells accumulate damaged mitochondria and deregulated ROS levels, which likely contribute to their tumor-initiating capacity. However, the role of autophagy in tumorigenesis is complex, as more recent work also revealed tumor dependence on autophagy: autophagy-competent mutant-Ras-expressing cells form tumors more efficiently than their autophagy-deficient counterparts; similarly, FIP200 deficiency suppresses PyMT-driven mammary tumorigenesis. These latter findings are attributed to the fact that tumors driven by powerful oncogenes have high metabolic demands catered to by autophagy. In this review, we discuss the relationship between ROS and autophagy and summarize our current knowledge on their functional interactions

The interplay between autophagy and ROS in tumorigenesis

International Nuclear Information System (INIS)

Kongara, Sameera; Karantza, Vassiliki

2012-01-01

Reactive oxygen species (ROS) at physiological levels are important cell signaling molecules. However, aberrantly high ROS are intimately associated with disease and commonly observed in cancer. Mitochondria are primary sources of intracellular ROS, and their maintenance is essential to cellular health. Autophagy, an evolutionarily conserved process whereby cytoplasmic components are delivered to lysosomes for degradation, is responsible for mitochondrial turnover and removal of damaged mitochondria. Impaired autophagy is implicated in many pathological conditions, including neurological disorders, inflammatory bowel disease, diabetes, aging, and cancer. The first reports connecting autophagy to cancer showed that allelic loss of the essential autophagy gene BECLIN1 (BECN1) is prevalent in human breast, ovarian, and prostate cancers and that Becn1 +/- mice develop mammary gland hyperplasias, lymphomas, lung and liver tumors. Subsequent studies demonstrated that Atg5 -/- and Atg7 -/- livers give rise to adenomas, Atg4C -/- mice are susceptible to chemical carcinogenesis, and Bif1 -/- mice are prone to spontaneous tumors, indicating that autophagy defects promote tumorigenesis. Due to defective mitophagy, autophagy-deficient cells accumulate damaged mitochondria and deregulated ROS levels, which likely contribute to their tumor-initiating capacity. However, the role of autophagy in tumorigenesis is complex, as more recent work also revealed tumor dependence on autophagy: autophagy-competent mutant-Ras-expressing cells form tumors more efficiently than their autophagy-deficient counterparts; similarly, FIP200 deficiency suppresses PyMT-driven mammary tumorigenesis. These latter findings are attributed to the fact that tumors driven by powerful oncogenes have high metabolic demands catered to by autophagy. In this review, we discuss the relationship between ROS and autophagy and summarize our current knowledge on their functional interactions in tumorigenesis.

PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

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Zuo, Li; Diaz, Philip T; Chien, Michael T; Roberts, William J; Kishek, Juliana; Best, Thomas M; Wagner, Peter D

2014-01-01

Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ∼30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses.

PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

Directory of Open Access Journals (Sweden)

Li Zuo

Full Text Available Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr followed by a high oxygen level (550 Torr, can reduce intracellular reactive oxygen species (ROS as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ∼30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses.

End-of-Life Care for Blood Cancers: A Series of Focus Groups With Hematologic Oncologists

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Odejide, Oreofe O.; Salas Coronado, Diana Y.; Watts, Corey D.; Wright, Alexi A.; Abel, Gregory A.

2014-01-01

Purpose: Hematologic cancers are associated with aggressive cancer-directed care near death and underuse of hospice and palliative care services. We sought to explore hematologic oncologists' perspectives and decision-making processes regarding end-of-life (EOL) care. Methods: Between September 2013 and January 2014, 20 hematologic oncologists from the Dana-Farber/Harvard Cancer Center participated in four focus groups regarding EOL care for leukemia, lymphoma, multiple myeloma, and hematopoietic stem-cell transplantation. Focus groups employed a semistructured format with case vignettes and open-ended questions and were followed by thematic analysis. Results: Many participants felt that identifying the EOL phase for patients with hematologic cancers was challenging as a result of the continuing potential for cure with advanced disease and the often rapid pace of decline near death. This difficulty was reported to result in later initiation of EOL care. Barriers to high-quality EOL care were also reported to be multifactorial, including unrealistic expectations from both physicians and patients, long-term patient-physician relationships resulting in difficulty conducting EOL discussions, and inadequacy of existing home-based EOL services. Participants also expressed concern that some EOL quality measures developed for solid tumors may be unacceptable for patients with blood cancers given their unique needs at the EOL (eg, palliative transfusions). Conclusion: Our analysis suggests that hematologic oncologists need better clinical markers for when to initiate EOL care. In addition, current quality measures may be inappropriate for identifying overly aggressive care for patients with blood cancers. Further research is needed to develop effective interventions to improve EOL care for this patient population. PMID:25294393

Definitive Stereotactic Body Radiotherapy (SBRT) for Extracranial Oligometastases: An International Survey of >1000 Radiation Oncologists.

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Lewis, Stephen L; Porceddu, Sandro; Nakamura, Naoki; Palma, David A; Lo, Simon S; Hoskin, Peter; Moghanaki, Drew; Chmura, Steven J; Salama, Joseph K

2017-08-01

Stereotactic body radiotherapy (SBRT) is often used to treat patients with oligometastases (OM). Yet, patterns of SBRT practice for OM are unknown. Therefore, we surveyed radiation oncologists internationally, to understand how and when SBRT is used for OM. A 25-question survey was distributed to radiation oncologists. Respondents using SBRT for OM were asked how long they have been treating OM, number of patients treated, organs treated, primary reason for use, doses used, and future intentions. Respondents not using SBRT for OM were asked reasons why SBRT was not used and intentions for future adoption. Data were analyzed anonymously. We received 1007 surveys from 43 countries. Eighty-three percent began using SBRT after 2005 and greater than one third after 2010. Eighty-four percent cited perceived treatment response/durability as the primary reason for using SBRT in OM patients. Commonly treated organs were lung (90%), liver (75%), and spine (70%). SBRT dose/fractionation schemes varied widely. Most would offer a second course to new OM. Nearly all (99%) planned to continue and 66% planned to increase SBRT for OM. Of those not using SBRT, 59% plan to start soon. The most common reason for not using SBRT was lack of clinical efficacy (48%) or lack of necessary image guidance equipment (34%). Radiation oncologists are increasingly using SBRT for OM. The main reason for not using SBRT for OM is a perceived lack of evidence demonstrating clinical advantages. These data strengthen the need for robust prospective clinical trials (ongoing and in development) to demonstrate clinical efficacy given the widespread adoption of SBRT for OM.

ROS signaling and stomatal movement in plant responses to drought stress and pathogen attack.

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Qi, Junsheng; Song, Chun-Peng; Wang, Baoshan; Zhou, Jianmin; Kangasjärvi, Jaakko; Zhu, Jian-Kang; Gong, Zhizhong

2018-04-16

Stomata, the pores formed by a pair of guard cells, are the main gateways for water transpiration and photosynthetic CO 2 exchange, as well as pathogen invasion in land plants. Guard cell movement is regulated by a combination of environmental factors including water status, light, CO 2 levels and pathogen attack, as well as endogenous signals such as abscisic acid and apoplastic reactive oxygen species (ROS). Under abiotic and biotic stress conditions, extracellular ROS are mainly produced by plasma membrane-localized NADPH oxidases, whereas intracellular ROS are produced in multiple organelles. These ROS form a sophisticated cellular signaling network, with the accumulation of apoplastic ROS an early hallmark of stomatal movement. Here, we review recent progress in understanding the molecular mechanisms of the ROS signaling network, primarily during drought stress and pathogen attack. We summarize the roles of apoplastic ROS in regulating stomatal movement, ABA and CO 2 signaling, and immunity responses. Finally, we discuss ROS accumulation and communication between organelles and cells. This information provides a conceptual framework for understanding how ROS signaling is integrated with various signaling pathways during plant responses to abiotic and biotic stress stimuli. This article is protected by copyright. All rights reserved.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography-Based Radiotherapy Target Volume Definition in Non-Small-Cell Lung Cancer: Delineation by Radiation Oncologists vs. Joint Outlining With a PET Radiologist?

International Nuclear Information System (INIS)

Hanna, Gerard G.; Carson, Kathryn J.; Lynch, Tom; McAleese, Jonathan; Cosgrove, Vivian P.; Eakin, Ruth L.; Stewart, David P.; Zatari, Ashraf; O'Sullivan, Joe M.; Hounsell, Alan R.

2010-01-01

Purpose: 18 F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has benefits in target volume (TV) definition in radiotherapy treatment planning (RTP) for non-small-cell lung cancer (NSCLC); however, an optimal protocol for TV delineation has not been determined. We investigate volumetric and positional variation in gross tumor volume (GTV) delineation using a planning PET/CT among three radiation oncologists and a PET radiologist. Methods and Materials: RTP PET/CT scans were performed on 28 NSCLC patients (Stage IA-IIIB) of which 14 patients received prior induction chemotherapy. Three radiation oncologists and one PET radiologist working with a fourth radiation oncologist independently delineated the GTV on CT alone (GTV CT ) and on fused PET/CT images (GTV PETCT ). The mean percentage volume change (PVC) between GTV CT and GTV PETCT for the radiation oncologists and the PVC between GTV CT and GTV PETCT for the PET radiologist were compared using the Wilcoxon signed-rank test. Concordance index (CI) was used to assess both positional and volume change between GTV CT and GTV PETCT in a single measurement. Results: For all patients, a significant difference in PVC from GTV CT to GTV PETCT exists between the radiation oncologist (median, 5.9%), and the PET radiologist (median, -0.4%, p = 0.001). However, no significant difference in median concordance index (comparing GTV CT and GTV FUSED for individual cases) was observed (PET radiologist = 0.73; radiation oncologists = 0.66; p = 0.088). Conclusions: Percentage volume changes from GTV CT to GTV PETCT were lower for the PET radiologist than for the radiation oncologists, suggesting a lower impact of PET/CT in TV delineation for the PET radiologist than for the oncologists. Guidelines are needed to standardize the use of PET/CT for TV delineation in RTP.

18F-fluorodeoxyglucose positron emission tomography/computed tomography-based radiotherapy target volume definition in non-small-cell lung cancer: delineation by radiation oncologists vs. joint outlining with a PET radiologist?

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Hanna, Gerard G; Carson, Kathryn J; Lynch, Tom; McAleese, Jonathan; Cosgrove, Vivian P; Eakin, Ruth L; Stewart, David P; Zatari, Ashraf; O'Sullivan, Joe M; Hounsell, Alan R

2010-11-15

(18)F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has benefits in target volume (TV) definition in radiotherapy treatment planning (RTP) for non-small-cell lung cancer (NSCLC); however, an optimal protocol for TV delineation has not been determined. We investigate volumetric and positional variation in gross tumor volume (GTV) delineation using a planning PET/CT among three radiation oncologists and a PET radiologist. RTP PET/CT scans were performed on 28 NSCLC patients (Stage IA-IIIB) of which 14 patients received prior induction chemotherapy. Three radiation oncologists and one PET radiologist working with a fourth radiation oncologist independently delineated the GTV on CT alone (GTV(CT)) and on fused PET/CT images (GTV(PETCT)). The mean percentage volume change (PVC) between GTV(CT) and GTV(PETCT) for the radiation oncologists and the PVC between GTV(CT) and GTV(PETCT) for the PET radiologist were compared using the Wilcoxon signed-rank test. Concordance index (CI) was used to assess both positional and volume change between GTV(CT) and GTV(PETCT) in a single measurement. For all patients, a significant difference in PVC from GTV(CT) to GTV(PETCT) exists between the radiation oncologist (median, 5.9%), and the PET radiologist (median, -0.4%, p = 0.001). However, no significant difference in median concordance index (comparing GTV(CT) and GTV(FUSED) for individual cases) was observed (PET radiologist = 0.73; radiation oncologists = 0.66; p = 0.088). Percentage volume changes from GTV(CT) to GTV(PETCT) were lower for the PET radiologist than for the radiation oncologists, suggesting a lower impact of PET/CT in TV delineation for the PET radiologist than for the oncologists. Guidelines are needed to standardize the use of PET/CT for TV delineation in RTP. Copyright © 2010 Elsevier Inc. All rights reserved.

Involvement of reactive oxygen species (ROS) in the induction of genetic instability by radiation

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Tominaga, Hideyuki; Kodama, Seiji; Suzuki, Keiji; Watanabe, Masami; Matsuda, Naoki

2004-01-01

Radiation generates reactive oxygen species (ROS) that interact with cellular molecules, including DNA, lipids, and proteins. To know how ROS contribute to the induction of genetic instability, we examined the effect of the anti-ROS condition, using both ascorbic acid phosphate (APM) treatment or a low oxygen condition, on the induction of delayed reproductive cell death and delayed chromosome aberrations. The primary surviving colonies of mouse m5S-derived cl. 2011-14 cells irradiated with 6 Gy of X-rays were replated and allowed to form secondary colonies. The anti-ROS treatments were applied to either preirradiation culture or postirradiation cultures for primary or secondary colony formation. Both anti-ROS conditions relieved X-ray-induced acute cell killing to a similar extent. These anti-ROS conditions also relieved genetic instability when those conditions were applied during primary colony formation. However, no effect was observed when the conditions were applied during preirradiation culture and secondary colony formation. We also demonstrated that the amounts of ROS in X-ray-irradiated cells rapidly increase and then decrease at 6 hr postirradiation, and the levels of ROS then gradually decrease to a baseline within 2 weeks. The APM treatment kept the ROS production at a lower level than an untreated control. These results suggest that the cause of genetic instability might be fixed by ROS during a 2-week postirradiation period. (author)

Nanomedicine in the ROS-mediated pathophysiology: Applications and clinical advances.

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Nash, Kevin M; Ahmed, Salahuddin

2015-11-01

Reactive oxygen species (ROS) are important in regulating normal cell physiological functions, but when produced in excess lead to the augmented pathogenesis of various diseases. Among these, ischemia reperfusion injury, Alzheimer's disease and rheumatoid arthritis are particularly important. Since ROS can be counteracted by a variety of antioxidants, natural and synthetic antioxidants have been developed. However, due to the ubiquitous production of ROS in living systems, poor in vivo efficiency of these agents and lack of target specificity, the current clinical modalities to treat oxidative stress damage are limited. Advances in the developing field of nanomedicine have yielded nanoparticles that can prolong antioxidant activity, and target specificity of these agents. This article reviews recent advances in antioxidant nanoparticles and their applications to manage oxidative stress-mediated diseases. Production of reactive oxygen species (ROS) is a purely physiological process in many disease conditions. However, excessive and uncontrolled production will lead to oxidative stress and further tissue damage. Advances in nanomedicine have provided many novel strategies to try to combat and counteract ROS. In this review article, the authors comprehensively highlighted the current status and future developments in using nanotechnology for providing novel therapeutic options in this field. Copyright © 2015 Elsevier Inc. All rights reserved.

The Role of Reactive Oxygen Species (ROS in the Biological Activities of Metallic Nanoparticles

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Ahmed Abdal Dayem

2017-01-01

Full Text Available Nanoparticles (NPs possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS. The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices.

Management of Cervical Cancer: Strategies for Limited-Resource Centres - A Guide for Radiation Oncologists

International Nuclear Information System (INIS)

2013-01-01

Cervical cancer remains a significant cause of morbidity and mortality among women globally, even though it is the cancer with the greatest demonstrated potential for secondary prevention. In some regions of the world the incidence is alarmingly high, such as in sub-Saharan Africa, some countries in Latin America, India and South-East Asia. This disease is highly preventable and curable at a relatively low risk and low cost when screening of asymptomatic women is available, together with appropriate diagnosis, treatment and follow-up. In developing clinical guidelines, the International Atomic Energy Agency (IAEA) has selected forms of cancer or clinical situations that are very common in low and middle income Member States and for which radiation oncologists consistently express a need for guidance. Clinical guidelines for the management of cervical cancer do exist in the published literature. However, these guidelines have usually been developed in and for affluent environments where all modern diagnosis and treatment modalities are available for the practitioner. In limited resource environments, the radiation oncologist is faced with the question, what would be the minimally acceptable line of action with the limited resources available? Clinical guidelines focusing on low and middle income countries provide a practical tool to these practitioners. This publication is aimed at the radiation oncologist working in centres with limited resources and treating a large number of patients with cervical cancer on a daily basis. The approach and techniques are intended to be simple, feasible and resource sparing to the extent that this is possible when dealing with a complex treatment modality. The Division of Human Health is placing special emphasis on the subject of cervical cancer, which is addressed not only in this guide but also in regional training courses and coordinated research projects on the subject

ROS1 Expression in Invasive Ductal Carcinoma of the Breast Related to Proliferation Activity

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Eom, Minseob; Lkhagvadorj, Sayamaa; Oh, Sung Soo; Han, Airi; Park, Kwang Hwa

2013-01-01

Purpose ROS1 is an oncogene, expressed primarily in glioblastomas of the brain that has been hypothesized to mediate the effects of early stage tumor progression. In addition, it was reported that ROS1 expression was observed in diverse cancer tissue or cell lines and ROS1 is associated with the development of several tumors. However, ROS1 expression has not been studied in breast cancer to date. Therefore, we investigated ROS1 expression at the protein and gene level to compare expression pa...

Differences in treatment patterns among patients with castration-resistant prostate cancer treated by oncologists versus urologists in a US managed care population

International Nuclear Information System (INIS)

Engel-Nitz, Nicole M; Alemayehu, Berhanu; Parry, David; Nathan, Faith

2011-01-01

Differences in treatment patterns, health care resource utilization, and costs between patients with castration-resistant prostate cancer (CRPC) treated by oncologists and those treated by urologists were examined. Patients aged ≥40 with CRPC were identified using claims from a large US managed health care plan between July 2001 and December 2007. A 6-month baseline period was used to assess patient characteristics. Patients with visits to an urologist, without visits to an oncologist, were assigned to the urology cohort, and patients with visits to an oncologist, with or without visits to an urologist, were assigned to the oncology cohort. Treatment patterns, health care resource utilization, and costs during a variable follow-up period were compared between cohorts using descriptive statistics and Lin’s regression. The urology cohort had fewer comorbid illnesses (P < 0.001) and patients were less likely to have other cancers during baseline (P < 0.001) or to die during follow-up (P = 0.004) compared with the oncology cohort. The oncology cohort patients were significantly more likely to have a claim for hormones (74.5% vs 61.1%; P < 0.001), chemotherapy (46.9% vs 10.2%, P < 0.001), and radiation (22.3% vs 3.7%, P < 0.0001) over follow-up. Mean unadjusted health care costs were higher in the oncology vs the urology cohort (US$31,896 vs US$15,318, respectively; P < 0.001). At 6 years follow-up, cumulative adjusted CRPC-specific costs were significantly higher among patients treated by oncologists with chemotherapy than among patients treated by urologists. CRPC patients treated by oncologists had greater use of hormones, chemotherapy, and radiation; higher percentages of patients with inpatient stays, emergency room, and ambulatory visits; and higher health care costs, than patients treated by urologists

Identification and characterisation of ROS modulator 1 in Lampetra japonica.

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Zhao, Chunhui; Feng, Bin; Cao, Ying; Xie, Peng; Xu, Jie; Pang, Yue; Liu, Xin; Li, Qingwei

2013-08-01

Reactive oxygen species (ROS) are a heterogeneous group of highly reactive molecules that oxidise targets in biological systems. ROS are also considered important immune regulators. In this study, we identified a homologue of reactive oxygen species modulator 1 (Romo1) in the Japanese lamprey (Lampetra japonica). The L japonica Romo1 (Lj-Romo1) gene shares high sequence homology with the Romo1 genes of jawed vertebrates. Real-time quantitative PCR demonstrated the wide distribution of Lj-Romo1 in lamprey tissues. Furthermore, after the lampreys were stimulated with lipopolysaccharide (LPS), the level of Lj-Romo1 mRNA was markedly up-regulated in the liver, gill, kidney, and intestine tissues. Lj-Romo1 was localised to the mitochondria and has the capacity to increase the ROS level in cells. The results obtained in the present study will help us to understand the roles of Romo1 in ROS production and innate immune responses in jawless vertebrates. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lysosome-controlled efficient ROS overproduction against cancer cells with a high pH-responsive catalytic nanosystem

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Fu, Jingke; Shao, Yiran; Wang, Liyao; Zhu, Yingchun

2015-04-01

Excess reactive oxygen species (ROS) have been proved to damage cancer cells efficiently. ROS overproduction is thus greatly desirable for cancer therapy. To date, ROS production is generally uncontrollable and outside cells, which always bring severe side-effects in the vasculature. Since most ROS share a very short half-life and primarily react close to their site of formation, it would be more efficient if excess ROS are controllably produced inside cancer cells. Herein, we report an efficient lysosome-controlled ROS overproduction via a pH-responsive catalytic nanosystem (FeOx-MSNs), which catalyze the decomposition of H2O2 to produce considerable ROS selectively inside the acidic lysosomes (pH 5.0) of cancer cells. After a further incorporation of ROS-sensitive TMB into the nanosystem (FeOx-MSNs-TMB), both a distinct cell labeling and an efficient death of breast carcinoma cells are obtained. This lysosome-controlled efficient ROS overproduction suggests promising applications in cancer treatments.Excess reactive oxygen species (ROS) have been proved to damage cancer cells efficiently. ROS overproduction is thus greatly desirable for cancer therapy. To date, ROS production is generally uncontrollable and outside cells, which always bring severe side-effects in the vasculature. Since most ROS share a very short half-life and primarily react close to their site of formation, it would be more efficient if excess ROS are controllably produced inside cancer cells. Herein, we report an efficient lysosome-controlled ROS overproduction via a pH-responsive catalytic nanosystem (FeOx-MSNs), which catalyze the decomposition of H2O2 to produce considerable ROS selectively inside the acidic lysosomes (pH 5.0) of cancer cells. After a further incorporation of ROS-sensitive TMB into the nanosystem (FeOx-MSNs-TMB), both a distinct cell labeling and an efficient death of breast carcinoma cells are obtained. This lysosome-controlled efficient ROS overproduction suggests

Breast cancer biology for the radiation oncologist

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Strauss, Jonathan [Northwestern Univ., Chicago, IL (United States). Dept. of Radiation Oncology; Small, William [Loyola Univ. Chicago, Maywood, IL (United States). Stritch School of Medicine, Cardianl Bernardin Cancer Center; Woloschak, Gayle E. (ed.) [Northwestern Univ. Feinberg, Chicago, IL (United States). School of Medicine

2015-10-01

This is the first textbook of its kind devoted to describing the biological complexities of breast cancer in a way that is relevant to the radiation oncologist. Radiation Oncology has long treated breast cancer as a single biological entity, with all treatment decisions being based on clinical and pathologic risk factors. We are now beginning to understand that biological subtypes of breast cancer may have different risks of recurrence as well as different intrinsic sensitivity to radiotherapy. Multi-gene arrays that have for years been used to predict the risk of distant recurrence and the value of systemic chemotherapy may also have utility in predicting the risk of local recurrence. Additionally, the targeted agents used to treat breast cancer may interact with radiotherapy in ways that can be beneficial or undesirable. All of these emerging issues are extensively discussed in this book, and practical evidence-based treatment recommendations are presented whenever possible.

Breast cancer biology for the radiation oncologist

International Nuclear Information System (INIS)

Strauss, Jonathan; Small, William; Woloschak, Gayle E.

2015-01-01

This is the first textbook of its kind devoted to describing the biological complexities of breast cancer in a way that is relevant to the radiation oncologist. Radiation Oncology has long treated breast cancer as a single biological entity, with all treatment decisions being based on clinical and pathologic risk factors. We are now beginning to understand that biological subtypes of breast cancer may have different risks of recurrence as well as different intrinsic sensitivity to radiotherapy. Multi-gene arrays that have for years been used to predict the risk of distant recurrence and the value of systemic chemotherapy may also have utility in predicting the risk of local recurrence. Additionally, the targeted agents used to treat breast cancer may interact with radiotherapy in ways that can be beneficial or undesirable. All of these emerging issues are extensively discussed in this book, and practical evidence-based treatment recommendations are presented whenever possible.

Attitudes toward end-of-life situations other than euthanasia and assisted suicide among Portuguese oncologists.

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Gonçalves, José António Ferraz

2010-10-01

The aim of this study was to determine the attitude of Portuguese oncologists toward end-of-life situations other than euthanasia and assisted suicide. This study used a survey of 450 Portuguese oncologists by postal means and personal contact. The response rate was 33% (143). Only 7.7% doctors would give lethal doses of drugs to someone with an incurable, advanced, and progressive disease that is unable to make decisions, at the request of a family member or other close person. However, 30 doctors (21.3%) would prefer, in the event they were in such a situation, that the drugs be given them at their request. None of the 12.4% who have received such requests admitted to committing any of those acts. Almost 70% of the doctors would withdraw life support measures at the patient's request if the same had an incurable, advanced, and progressive disease, and a further 14% would do it in certain circumstances, but only 41% would withdraw measures such as nutrition and hydration. Fewer doctors would withdraw such measures including nutrition and hydration at a family member's request or on their own initiative. Religion has a major influence on the doctors' opinion. Most doctors (96.5%) agreed with the administration of drugs for symptom control even foreseeing that they could shorten life. Most Portuguese oncologists respect patients' autonomy, favoring the withdrawal of life support treatment at the patients' request when appropriate and much less do so on the request of others or by their own initiative. They appropriately do not confuse those practices with symptom relief even when hastened death can be envisaged.

Investigation and analysis of oncologists' knowledge of morphine usage in cancer pain treatment

Directory of Open Access Journals (Sweden)

Liu W

2014-05-01

Full Text Available Weiran Liu,1,* Shumin Xie,2,* Lin Yue,3,* Jiahao Liu,2 Stephanie Mu-Lian Woo,4 Weilin Liu,2 Adam R Miller,5 Jing Zhang,6 Lijun Huang,7 Lei Zhang8,*1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Department of Anesthesia, Tianjin, People's Republic of China; 2The Xiangya Medical School of Central-South University, Changsha, People's Republic of China; 3Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Outpatient Service, Tianjin, People's Republic of China; 4Harvard University, Cambridge, MA, USA; 5Indiana University School of Medicine, Indianapolis, IN, USA; 6Tianjin Medical University, Tianjin, People's Republic of China; 7Hunan Provincial Tumor Hospital, Department of Lymphoma and Hematology, Changsha, People's Republic of China; 8Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Department of Thoracic Surgery, Tianjin, People's Republic of China *These authors contributed equally to this paperPurpose: To examine oncologists' knowledge of cancer pain and morphine's clinical application in the People's Republic of China. In addition, this study analyzes and discusses the negative factors that currently affect the clinical application of morphine.Patients and methods: A questionnaire survey was given to a random sample of 150 oncologists from Tianjin Medical University Cancer Institute and Hospital. The statistical results were analyzed and processed using SPSS version 21.0 and Matlab version 2012a statistical software. Single-factor analysis of variance, Kruskal–Wallis nonparametric test, and independent samples t-test were adopted to analyze the difference in knowledge scores of morphine usage. The study

Recent advances in intracellular and in vivo ROS sensing: focus on nanoparticle and nanotube applications.

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Uusitalo, Larissa M; Hempel, Nadine

2012-01-01

Reactive oxygen species (ROS) are increasingly being implicated in the regulation of cellular signaling cascades. Intracellular ROS fluxes are associated with cellular function ranging from proliferation to cell death. Moreover, the importance of subtle, spatio-temporal shifts in ROS during localized cellular signaling events is being realized. Understanding the biochemical nature of the ROS involved will enhance our knowledge of redox-signaling. An ideal intracellular sensor should therefore resolve real-time, localized ROS changes, be highly sensitive to physiologically relevant shifts in ROS and provide specificity towards a particular molecule. For in vivo applications issues such as bioavailability of the probe, tissue penetrance of the signal and signal-to-noise ratio also need to be considered. In the past researchers have heavily relied on the use of ROS-sensitive fluorescent probes and, more recently, genetically engineered ROS sensors. However, there is a great need to improve on current methods to address the above issues. Recently, the field of molecular sensing and imaging has begun to take advantage of the unique physico-chemical properties of nanoparticles and nanotubes. Here we discuss the recent advances in the use of these nanostructures as alternative platforms for ROS sensing, with particular emphasis on intracellular and in vivo ROS detection and quantification.

Crosstalk between Rac1-mediated actin regulation and ROS production.

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Acevedo, Alejandro; González-Billault, Christian

2018-02-20

The small RhoGTPase Rac1 is implicated in a variety of events related to actin cytoskeleton rearrangement. Remarkably, another event that is completely different from those related to actin regulation has the same relevance; the Rac1-mediated production of reactive oxygen species (ROS) through NADPH oxidases (NOX). Each outcome involves different Rac1 downstream effectors; on one hand, events related to the actin cytoskeleton require Rac1 to bind to WAVEs proteins and PAKs that ultimately promote actin branching and turnover, on the other, NOX-derived ROS production demands active Rac1 to be bound to a cytosolic activator of NOX. How Rac1-mediated signaling ends up promoting actin-related events, NOX-derived ROS, or both is poorly understood. Rac1 regulators, including scaffold proteins, are known to exert tight control over its functions. Hence, evidence of Rac1 regulatory events leading to both actin remodeling and NOX-mediated ROS generation are discussed. Moreover, cellular functions linked to physiological and pathological conditions that exhibit crosstalk between Rac1 outcomes are analyzed, while plausible roles in neuronal functions (and dysfunctions) are highlighted. Together, discussed evidence shed light on cellular mechanisms which requires Rac1 to direct either actin- and/or ROS-related events, helping to understand crucial roles of Rac1 dual functionality. Copyright © 2018 Elsevier Inc. All rights reserved.

Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing.

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Janda, Jaroslav; Nfonsam, Valentine; Calienes, Fernanda; Sligh, James E; Jandova, Jana

2016-05-01

Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured ρ(0) fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds.

Role of Mitochondrial Reverse Electron Transport in ROS Signaling: Potential Roles in Health and Disease

Directory of Open Access Journals (Sweden)

Filippo Scialò

2017-06-01

Full Text Available Reactive Oxygen Species (ROS can cause oxidative damage and have been proposed to be the main cause of aging and age-related diseases including cancer, diabetes and Parkinson's disease. Accordingly, mitochondria from old individuals have higher levels of ROS. However, ROS also participate in cellular signaling, are instrumental for several physiological processes and boosting ROS levels in model organisms extends lifespan. The current consensus is that low levels of ROS are beneficial, facilitating adaptation to stress via signaling, whereas high levels of ROS are deleterious because they trigger oxidative stress. Based on this model the amount of ROS should determine the physiological effect. However, recent data suggests that the site at which ROS are generated is also instrumental in determining effects on cellular homeostasis. The best example of site-specific ROS signaling is reverse electron transport (RET. RET is produced when electrons from ubiquinol are transferred back to respiratory complex I, reducing NAD+ to NADH. This process generates a significant amount of ROS. RET has been shown to be instrumental for the activation of macrophages in response to bacterial infection, re-organization of the electron transport chain in response to changes in energy supply and adaptation of the carotid body to changes in oxygen levels. In Drosophila melanogaster, stimulating RET extends lifespan. Here, we review what is known about RET, as an example of site-specific ROS signaling, and its implications for the field of redox biology.

Rosé wine volatile composition and the preferences of Chinese wine professionals.

Science.gov (United States)

Wang, Jiaming; Capone, Dimitra L; Wilkinson, Kerry L; Jeffery, David W

2016-07-01

Rosé wine aromas range from fruity and floral, to more developed, savoury characters. Lighter than red wines, rosé wines tend to match well with Asian cuisines, yet little is known about the factors driving desirability of rosé wines in emerging markets such as China. This study involved Chinese wine professionals participating in blind rosé wine tastings comprising 23 rosé wines from Australia, China and France in three major cities in China. According to the sensory results, a link between the preference, quality and expected retail price of the wines was observed, and assessors preferred wines with prominent red fruit, floral, confectionery and honey characters, and without developed attributes or too much sweetness. Basic wine chemical parameters and 47 volatile compounds, including 5 potent thiols, were determined. Correlations between chemical components, sensory attributes and preference/quality/expected price were visualised by network analysis, revealing relationships that are worthy of further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of prostate-specific membrane antigen positron emission tomography on the decision-making of radiation oncologists.

Science.gov (United States)

Shakespeare, Thomas P

2015-11-18

Positron emission tomography (PET) imaging is routinely used in many cancer types, although is not yet a standard modality for prostate carcinoma. Prostate-specific membrane antigen (PSMA) PET is a promising new modality for staging prostate cancer, with recent studies showing potential advantages over traditional computed tomography (CT), magnetic resonance imaging (MRI) and nuclear medicine bone scan imaging. However, the impact of PSMA PET on the decision-making of radiation oncologists and outcomes after radiotherapy is yet to be determined. Our aim was to determine the impact of PSMA PET on a radiation oncologist's clinical practice. Patients in a radiation oncology clinic who underwent PSMA PET were prospectively recorded in an electronic oncology record. Patient demographics, outcomes of imaging, and impact on decision-making were evaluated. Fifty-four patients underwent PSMA PET between January and May 2015. The major reasons for undergoing PET included staging before definitive (14.8%) or post-prostatectomy (33.3%) radiotherapy, and investigation of PSA failures following definitive (16.7%) or post-prostatectomy (33.3%) radiotherapy. In 46.3% of patients PSMA was positive after negative traditional imaging, in 9.3% PSMA was positive after equivocal imaging, and in 13.0% PSMA was negative after equivocal imaging. PSMA PET changed radiotherapy management in 46.3% of cases, and hormone therapy in 33.3% of patients, with an overall change in decision-making in 53.7% of patients. PSMA PET has the potential to significantly alter the decision-making of radiation oncologists, and may become a valuable imaging tool in the future.

A preliminary cyber-physical security assessment of the Robot Operating System (ROS)

Science.gov (United States)

McClean, Jarrod; Stull, Christopher; Farrar, Charles; Mascareñas, David

2013-05-01

Over the course of the last few years, the Robot Operating System (ROS) has become a highly popular software framework for robotics research. ROS has a very active developer community and is widely used for robotics research in both academia and government labs. The prevalence and modularity of ROS cause many people to ask the question: "What prevents ROS from being used in commercial or government applications?" One of the main problems that is preventing this increased use of ROS in these applications is the question of characterizing its security (or lack thereof). In the summer of 2012, a crowd sourced cyber-physical security contest was launched at the cyber security conference DEF CON 20 to begin the process of characterizing the security of ROS. A small-scale, car-like robot was configured as a cyber-physical security "honeypot" running ROS. DEFFCON-20 attendees were invited to find exploits and vulnerabilities in the robot while network traffic was collected. The results of this experiment provided some interesting insights and opened up many security questions pertaining to deployed robotic systems. The Federal Aviation Administration is tasked with opening up the civil airspace to commercial drones by September 2015 and driverless cars are already legal for research purposes in a number of states. Given the integration of these robotic devices into our daily lives, the authors pose the following question: "What security exploits can a motivated person with little-to-no experience in cyber security execute, given the wide availability of free cyber security penetration testing tools such as Metasploit?" This research focuses on applying common, low-cost, low-overhead, cyber-attacks on a robot featuring ROS. This work documents the effectiveness of those attacks.

Supporting patients in obtaining and oncologists in providing evidence-based health-related quality of life information prior to and after esophageal cancer surgery

OpenAIRE

Jacobs, M.

2015-01-01

The overall aim of this thesis was to support patients in obtaining and oncologists in providing evidence-based HRQL data prior to and following esophageal cancer surgery. This thesis is divided in two parts. In Part I, we addressed the information needs of esophageal cancer patients prior to and following esophageal surgery, the barriers and facilitators patients experienced when discussing their information needs with their oncologist, and the development of a web-based question prompt shee...

The importance of good death components among cancer patients, the general population, oncologists, and oncology nurses in Japan: patients prefer "fighting against cancer".

Science.gov (United States)

Miyashita, Mitsunori; Kawakami, Sachiko; Kato, Daiki; Yamashita, Hideomi; Igaki, Hiroshi; Nakano, Kimiko; Kuroda, Yujiro; Nakagawa, Keiichi

2015-01-01

The objectives of this study were to compare the importance of components of a good death among cancer patients, the general population, oncologists, and oncology nurses, and explore which patients preferred "fighting against cancer." We conducted a cross-sectional anonymous self-reported survey of cancer patients who visited a radiation oncology outpatient clinic, oncologists, and oncology nurses at the Tokyo University Hospital and a random sample of the general population in the Tokyo metropolitan area. The outcomes were 18 previously developed components of a good death in Japanese cancer care consisting of 57 attributes. Three hundred ten patients, 353 subjects from the general population, 109 oncologists, and 366 oncology nurses participated. The desire to "fight against cancer" was highly significantly different between patients and oncologists (effect size [ES] = -1.40; P = 0.001) and patients and oncology nurses (ES = -1.12; P = 0.001). "Physical and cognitive control" was, similarly, highly significantly different between patients and oncologists (ES = -1.30; P = 0.001) and patients and oncology nurses (ES = -1.06; P = 0.001). Patients who emphasized "maintaining hope and pleasure" (P = 0.0001), "unawareness of death" (P = 0.0001), and "good relationship with family" (P = 0.004) favored "fighting against cancer." The patients, however, who emphasized "physical and psychological comfort" did not significantly favor "fighting against cancer" (P = 0.004). The importance of good death components differed between groups. Medical professionals should be aware of the diversity of values surrounding death and assess the patient's values and discuss them to support his or her quality of life. In addition, the development of care and a medical/social system to maintain hope and pleasure after failure of anticancer treatment is necessary.

Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases

Directory of Open Access Journals (Sweden)

Zhong-Wei Zhang

2016-01-01

Full Text Available Reactive oxygen species (ROS play a crucial role in the inflammatory response and cytokine outbreak, such as during virus infections, diabetes, cancer, cardiovascular diseases, and neurodegenerative diseases. Therefore, antioxidant is an important medicine to ROS-related diseases. For example, ascorbic acid (vitamin C, VC was suggested as the candidate antioxidant to treat multiple diseases. However, long-term use of high-dose VC causes many side effects. In this review, we compare and analyze all kinds of mitochondrion-permeable antioxidants, including edaravone, idebenone, α-Lipoic acid, carotenoids, vitamin E, and coenzyme Q10, and mitochondria-targeted antioxidants MitoQ and SkQ and propose astaxanthin (a special carotenoid to be the best antioxidant for ROS-burst-mediated acute diseases, like avian influenza infection and ischemia-reperfusion. Nevertheless, astaxanthins are so unstable that most of them are inactivated after oral administration. Therefore, astaxanthin injection is suggested hypothetically. The drawbacks of the antioxidants are also reviewed, which limit the use of antioxidants as coadjuvants in the treatment of ROS-associated disorders.

Current Practice Patterns Surrounding Fertility Concerns in Stage I Seminoma Patients: Survey of United States Radiation Oncologists.

Science.gov (United States)

Post, Carl M; Jain, Aditya; Degnin, Catherine; Chen, Yiyi; Craycraft, Mike; Hung, Arthur Y; Jaboin, Jerry J; Thomas, Charles R; Mitin, Timur

2018-01-16

Patients with testicular seminoma may face fertility issues because of their underlying disease as well as treatments they undergo. The current patterns of practice among U.S. radiation oncologists aimed at assessing and preserving fertility in patients with Stage I seminoma are unknown. We surveyed practicing U.S. radiation oncologists via an Institutional Review Board-approved online questionnaire. Respondents' characteristics and perceived patient infertility rates were analyzed for association with treatment recommendations. We received 353 responses, of whom one quarter (23%) consider themselves experts. A vast majority (84%) recommend observation as a default strategy. Fifty-two percent routinely advise fertility assessment for patients before observation or chemotherapy, and 74% routinely do so before adjuvant radiation therapy (RT). Forty-one percent and 43% believe that 10% and 30% of patients are infertile following orchiectomy, respectively. Thirty-seven percent and 22% believe infertility rates following para-aortic RT to be 30% and 50%, respectively. Eighty percent routinely use clamshell scrotal shielding. Responders with higher perceived infertility rates are more likely to recommend fertility assessment/sperm banking (Fisher's exact p < 0.0001). Responders who routinely advised fertility assessment were more likely to use clamshell shielding (Cochran-Armitage trend test p = 0.0007). Clamshell use was positively correlated with higher perceived infertility rates following para-aortic RT (Spearman's correlation coefficient = 0.006). Despite a clear knowledge of fertility issues in men diagnosed with seminoma, there is no universal adoption of fertility assessment among U.S. radiation oncologists.

Menadione 処理した Candida albicans ROS 生産機構の解析

OpenAIRE

上野, 将明; 小笠原, 綾子; 渡部, 俊彦; 三上, 健; 松本, 達二; ウエノ, ユキヒロ; オガサワラ, アヤコ; ワタナベ, トシユキ; ミカミ, タケシ; マツモト, タツジ; Yukihiro, UENO; Ayako, OGASAWARA; Toshihiko, WATANABE; Takeshi, MIKAMI; Tatsuji, MATSUMOTO

2008-01-01

Menadione shows anti Condida activity by promoting ROS production. However, the ROS production mechanism has not been clarifield. Thus, in this study, we studied thr relation between anti Candida activity of menadione and ROS production. Menadione inhibited the growth of C. albicans BWP17 strain, the growth of C. albicans JM02 strain was not inhibited. ROS production in C. albicans BWP17 strain was enhanced by addition of menadione. The ROS production in C. albicans JM02 strain was also enhan...

Prostate positioning using cone-beam computer tomography based on manual soft-tissue registration. Interobserver agreement between radiation oncologists and therapists

Energy Technology Data Exchange (ETDEWEB)

Jereczek-Fossa, B.A.; Pobbiati, C.; Fanti, P. [European Institute of Oncology, Department of Radiation Oncology, Milan (Italy); University of Milan, Milan (Italy); Santoro, L. [European Institute of Oncology, Department of Epidemiology and Biostatistics, Milan (Italy); Fodor, C.; Zerini, D. [European Institute of Oncology, Department of Radiation Oncology, Milan (Italy); Vigorito, S. [European Institute of Oncology, Department of Medical Physics, Milan (Italy); Baroni, G. [Politecnico di Milano, Department of Electronics Information and Bioengineering, Milan (Italy); De Cobelli, O. [European Institute of Oncology, Department of Urology, Milan (Italy); University of Milan, Milan (Italy); Orecchia, R. [European Institute of Oncology, Department of Radiation Oncology, Milan (Italy); National Center for Oncological Hadrontherapy (CNAO) Foundation, Pavia (Italy); University of Milan, Milan (Italy)

2014-01-15

To check the interobserver agreement between radiation oncologists and therapists (RTT) using an on- and off-line cone-beam computer tomography (CBCT) protocol for setup verification in the radiotherapy of prostate cancer. The CBCT data from six prostate cancer patients treated with hypofractionated intensity-modulated radiotherapy (IMRT) were independently reviewed off-line by four observers (one radiation oncologist, one junior and two senior RTTs) and benchmarked with on-line CBCT positioning performed by a radiation oncologist immediately prior to treatment. CBCT positioning was based on manual soft-tissue registration. Agreement between observers was evaluated using weighted Cohen's kappa statistics. In total, 152 CBCT-based prostate positioning procedures were reviewed by each observer. The mean (± standard deviation) of the differences between off- and on-line CBCT-simCT registration translations along the three directions (antero-posterior, latero-lateral and cranio-caudal) and rotation around the antero-posterior axis were - 0.7 (3.6) mm, 1.9 (2.7) mm, 0.9 (3.6) mm and - 1.8 (5.0) degrees, respectively. Satisfactory interobserver agreement was found, being substantial (weighted kappa > 0.6) in 10 of 16 comparisons and moderate (0.41-0.60) in the remaining six comparisons. CBCT interpretation performed by RTTs is comparable to that of radiation oncologists. Our study might be helpful in the quality assurance of radiotherapy and the optimization of competencies. Further investigation should include larger sample sizes, a greater number of observers and validated methodology in order to assess interobserver variability and its impact on high-precision prostate cancer IGRT. In the future, it should enable the wider implementation of complex and evolving radiotherapy technologies. (orig.)

TiO{sub 2} nanoparticle-induced ROS correlates with modulated immune cell function

Energy Technology Data Exchange (ETDEWEB)

Maurer-Jones, Melissa A.; Christenson, Jenna R.; Haynes, Christy L., E-mail: chaynes@umn.edu [University of Minnesota, Department of Chemistry (United States)

2012-12-15

Design of non-toxic nanoparticles will be greatly facilitated by understanding the nanoparticle-cell interaction mechanism on a cell function level. Mast cells are important cells for the immune system's first line of defense, and we can utilize their exocytotic behavior as a model cellular function as it is a conserved process across cell types and species. Perturbations in exocytosis can also have implications for whole organism health. One proposed mode of toxicity is nanoparticle-induced reactive oxygen species (ROS), particularly for titanium dioxide (TiO{sub 2}) nanoparticles. Herein, we have correlated changes in ROS with the perturbation of the critical cell function of exocytosis, using UV light to induce greater levels of ROS in TiO{sub 2} exposed cells. The primary culture mouse peritoneal mast cells (MPMCs) were exposed to varying concentrations of TiO{sub 2} nanoparticles for 24 h. ROS content was determined using 2,7-dihydrodichlorofluorescein diacetate (DCFDA). Cellular viability was determined with the MTT and Trypan blue assays, and exocytosis was measured by the analytical electrochemistry technique of carbon-fiber microelectrode amperometry. MPMCs exposed to TiO{sub 2} nanoparticles experienced a dose-dependent increase in total ROS content. While there was minimal impact of ROS on cellular viability, there is a correlation between ROS amount and exocytosis perturbation. As nanoparticle-induced ROS increases, there is a significant decrease (45 %) in the number of serotonin molecules being released during exocytosis, increase (26 %) in the amount of time for each exocytotic granule to release, and decrease (28 %) in the efficiency of granule trafficking and docking. This is the first evidence that nanoparticle-induced ROS correlates with chemical messenger molecule secretion, possibly making a critical connection between functional impairment and mechanisms contributing to that impairment.

High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.

Science.gov (United States)

Pailler, E; Auger, N; Lindsay, C R; Vielh, P; Islas-Morris-Hernandez, A; Borget, I; Ngo-Camus, M; Planchard, D; Soria, J-C; Besse, B; Farace, F

2015-07-01

Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged patients show considerable heterogeneity of ROS1-gene

Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft Tissue Sarcoma of the Extremity

Energy Technology Data Exchange (ETDEWEB)

Bahig, Houda [Department of Radiation Oncology, Centre Hospitalier de l' Université de Montréal, Montreal, QC (Canada); Roberge, David, E-mail: david.roberge.chum@ssss.gouv.qc.ca [Department of Radiation Oncology, Centre Hospitalier de l' Université de Montréal, Montreal, QC (Canada); Bosch, Walter [Department of Radiation Oncology, Washington University, St Louis, Missouri (United States); Levin, William [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Petersen, Ivy; Haddock, Michael [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Freeman, Carolyn [Division of Radiation Oncology, McGill University Health Centre, Montreal, QC (Canada); DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Indelicato, Danny J. [Department of Radiation Oncology, University of Florida Medical Center, Jacksonville, Florida (United States); Baldini, Elizabeth H. [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Hitchcock, Ying [Department of Radiation Oncology, University of Utah Medical Center, Salt Lake City, Utah (United States); Kirsch, David G. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Kozak, Kevin R. [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Wolfson, Aaron [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); and others

2013-06-01

Purpose: Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Methods and Materials: Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm{sup 3} (7-413 cm{sup 3}), 280 cm{sup 3} and 360 cm{sup 3}. The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm{sup 3} (24-565 cm{sup 3}) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm{sup 3} (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm{sup 3}, respectively. There were 3 large tumors with >30 cm{sup 3} of SE not included in the CTV3cm volume. Conclusion: Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant

Agreement among RTOG sarcoma radiation oncologists in contouring suspicious peritumoral edema for preoperative radiation therapy of soft tissue sarcoma of the extremity.

Science.gov (United States)

Bahig, Houda; Roberge, David; Bosch, Walter; Levin, William; Petersen, Ivy; Haddock, Michael; Freeman, Carolyn; Delaney, Thomas F; Abrams, Ross A; Indelicato, Danny J; Baldini, Elizabeth H; Hitchcock, Ying; Kirsch, David G; Kozak, Kevin R; Wolfson, Aaron; Wang, Dian

2013-06-01

Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm(3) (7-413 cm(3)), 280 cm(3) and 360 cm(3). The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm(3) (24-565 cm(3)) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm(3) (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm(3), respectively. There were 3 large tumors with >30 cm(3) of SE not included in the CTV3cm volume. Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE. Copyright © 2013 Elsevier Inc. All rights

Agreement Among RTOG Sarcoma Radiation Oncologists in Contouring Suspicious Peritumoral Edema for Preoperative Radiation Therapy of Soft Tissue Sarcoma of the Extremity

International Nuclear Information System (INIS)

Bahig, Houda; Roberge, David; Bosch, Walter; Levin, William; Petersen, Ivy; Haddock, Michael; Freeman, Carolyn; DeLaney, Thomas F.; Abrams, Ross A.; Indelicato, Danny J.; Baldini, Elizabeth H.; Hitchcock, Ying; Kirsch, David G.; Kozak, Kevin R.; Wolfson, Aaron

2013-01-01

Purpose: Peritumoral edema may harbor sarcoma cells. The extent of suspicious edema (SE) included in the treatment volume is subject to clinical judgment, balancing the risk of missing tumor cells with excess toxicity. Our goal was to determine variability in SE delineation by sarcoma radiation oncologists (RO). Methods and Materials: Twelve expert ROs were provided with T1 gadolinium and T2-weighted MR images of 10 patients with high-grade extremity soft-tissue sarcoma. Gross tumor volume, clinical target volume (CTV)3cm (3 cm longitudinal and 1.5 cm radial margin), and CTV2cm (2 cm longitudinal and 1 cm radial margin) were contoured by a single observer. Suspicious peritumoral edema, defined as abnormal signal on T2 images, was independently delineated by all 12 ROs. Contouring agreement was analyzed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. Results: The mean volumes of GTV, CTV2cm, and CTV3cm were, respectively, 130 cm 3 (7-413 cm 3 ), 280 cm 3 and 360 cm 3 . The mean consensus volume computed using the STAPLE algorithm at 95% confidence interval was 188 cm 3 (24-565 cm 3 ) with a substantial overall agreement corrected for chance (mean kappa = 0.71; range: 0.32-0.87). The minimum, maximum, and mean volume of SE (excluding the GTV) were 4, 182, and 58 cm 3 (representing a median of 29% of the GTV volume). The median volume of SE not included in the CTV2cm and in the CTV3cm was 5 and 0.3 cm 3 , respectively. There were 3 large tumors with >30 cm 3 of SE not included in the CTV3cm volume. Conclusion: Despite the fact that SE would empirically seem to be a more subjective volume, a substantial or near-perfect interobserver agreement was observed in SE delineation in most cases with high-grade soft-tissue sarcomas of the extremity. A median of 97% of the consensus SE is within the CTV2cm (99.8% within the CTV3cm). In a minority of cases, however, significant expansion of the CTVs is required to cover SE

Intracellular Redox Compartmentation and ROS-Related Communication in Regulation and Signaling.

Science.gov (United States)

Noctor, Graham; Foyer, Christine H

2016-07-01

Recent years have witnessed enormous progress in understanding redox signaling related to reactive oxygen species (ROS) in plants. The consensus view is that such signaling is intrinsic to many developmental processes and responses to the environment. ROS-related redox signaling is tightly wedded to compartmentation. Because membranes function as barriers, highly redox-active powerhouses such as chloroplasts, peroxisomes, and mitochondria may elicit specific signaling responses. However, transporter functions allow membranes also to act as bridges between compartments, and so regulated capacity to transmit redox changes across membranes influences the outcome of triggers produced at different locations. As well as ROS and other oxidizing species, antioxidants are key players that determine the extent of ROS accumulation at different sites and that may themselves act as signal transmitters. Like ROS, antioxidants can be transported across membranes. In addition, the intracellular distribution of antioxidative enzymes may be modulated to regulate or facilitate redox signaling appropriate to the conditions. Finally, there is substantial plasticity in organellar shape, with extensions such as stromules, peroxules, and matrixules playing potentially crucial roles in organelle-organelle communication. We provide an overview of the advances in subcellular compartmentation, identifying the gaps in our knowledge and discussing future developments in the area. © 2016 American Society of Plant Biologists. All Rights Reserved.

Troglitazone induced apoptosis via PPARγ activated POX-induced ROS formation in HT29 cells.

Science.gov (United States)

Wang, Jing; Lv, XiaoWen; Shi, JiePing; Hu, XiaoSong; DU, YuGuo

2011-08-01

In order to investigate the potential mechanisms in troglitazone-induced apoptosis in HT29 cells, the effects of PPARγ and POX-induced ROS were explored. [3- (4, 5)-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay, Annexin V and PI staining using FACS, plasmid transfection, ROS formation detected by DCFH staining, RNA interference, RT-PCR & RT-QPCR, and Western blotting analyses were employed to investigate the apoptotic effect of troglitazone and the potential role of PPARγ pathway and POX-induced ROS formation in HT29 cells. Troglitazone was found to inhibit the growth of HT29 cells by induction of apoptosis. During this process, mitochondria related pathways including ROS formation, POX expression and cytochrome c release increased, which were inhibited by pretreatment with GW9662, a specific antagonist of PPARγ. These results illustrated that POX upregulation and ROS formation in apoptosis induced by troglitazone was modulated in PPARγ-dependent pattern. Furthermore, the inhibition of ROS and apoptosis after POX siRNA used in troglitazone-treated HT29 cells indicated that POX be essential in the ROS formation and PPARγ-dependent apoptosis induced by troglitazone. The findings from this study showed that troglitazone-induced apoptosis was mediated by POX-induced ROS formation, at least partly, via PPARγ activation. Copyright © 2011 The Editorial Board of Biomedical and Environmental Sciences. Published by Elsevier B.V. All rights reserved.

TOR Complex 2-Ypk1 Signaling Maintains Sphingolipid Homeostasis by Sensing and Regulating ROS Accumulation

Directory of Open Access Journals (Sweden)

Brad J. Niles

2014-02-01

Full Text Available Reactive oxygen species (ROS are produced during normal metabolism and can function as signaling molecules. However, ROS at elevated levels can damage cells. Here, we identify the conserved target of rapamycin complex 2 (TORC2/Ypk1 signaling module as an important regulator of ROS in the model eukaryotic organism, S. cerevisiae. We show that TORC2/Ypk1 suppresses ROS produced both by mitochondria as well as by nonmitochondrial sources, including changes in acidification of the vacuole. Furthermore, we link vacuole-related ROS to sphingolipids, essential components of cellular membranes, whose synthesis is also controlled by TORC2/Ypk1 signaling. In total, our data reveal that TORC2/Ypk1 act within a homeostatic feedback loop to maintain sphingolipid levels and that ROS are a critical regulatory signal within this system. Thus, ROS sensing and signaling by TORC2/Ypk1 play a central physiological role in sphingolipid biosynthesis and in the maintenance of cell growth and viability.

Integration of early specialist palliative care in cancer care: Survey of oncologists, oncology nurses, and patients

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Naveen Salins

2016-01-01

Conclusion: Oncologists, oncology nurses, and patients felt that integration of early specialist palliative care in cancer improves symptom control, end-of-life care, health-related communication, and continuity of care. The perceptions of benefit of the palliative care intervention in the components surveyed, differed among the three groups.

SUSTANCIAS OXÍGENO REACTIVAS (ROS EN SEMEN CONGELADO-DESCONGELADO DE PORCINO

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Diana Vasco Mora

2008-06-01

Full Text Available La generación de ROS fue medida por citometría de flujo en muestras espermáticas descongeladas incubadas sin (niveles basales o con (niveles inducidos un inductor de ROS (1 mM de tert-butyl hidroperóxido por 30 min a 39 °C y 5% de CO2. Además, fueron simultáneamente teñidas con 2’, 7’-diacetato de diclorodihidrofluoresceína, acetil ester (1 mM, CM-H2DCFDA, para estimar la producción de ROS e, ioduro de propidio (1.5 mM para excluir la población espermática muerta. Los eyaculados de nueve verracos fueron congelados con 3% de glicerol y descongelados a ≈1200 ó ≈1800 ºC min-1. La producción de ROS fue medida a los 0, 60, 120, 240 y 360 min en muestras mantenidas a 21-23 °C (no incubadas, o a 39 ºC y 5% de CO2 (incubadas. La velocidad de descongelación no registró influencia (P>0.05 sobre la producción de ROS. La generación de ROS fue constante (P>0.05 en el tiempo en las muestras no incubadas, pero mostró un incremento progresivo en las muestras incubadas, siendo significativa (P<0.05 desde los 120 min en niveles basales ó 60 min de incubación en niveles inducidos. Además, una significativa variabilidad eyaculado/verraco fue evidente, tanto en niveles basales como inducidos en las muestras incubadas. La producción de ROS basal e inducida estuvo significativamente (P<0.01 correlacionada con la calidad espermática. La técnica utilizada es de gran utilidad para evaluar capacidad funcional en espermatozoides congelados-descongelados; sin embargo, se requieren estudios adicionales para estandarizar la misma y establecer umbrales indicativos de pérdida de calidad espermática.

Impact of social media for the hematologist/oncologist.

Science.gov (United States)

Abuhadra, Nour; Majhail, Navneet S; Nazha, Aziz

2017-10-01

In the era of modern communication, the physician and patient relationship has evolved to include an entirely new dimension-social media. This new dimension offers several opportunities for patient education, research and its dissemination, and professional development for health care providers; it can also serve as a platform for addressing important public health issues. However, these advantages come with challenges such as threats to patient and professional privacy. In this article, we dissect the benefits and drawbacks of this social evolution on the practicing hematologist-oncologist. We also perform a review of the current literature on the integration of social media in the practice of hematology/oncology; examine available guidelines for information exchange between health care professionals, industry, pharmaceutical companies, advocacy groups, and patients; and offer ways to create its seamless integration into clinical hematology-oncology practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of the prevalence of burnout and psychological morbidity among radiation oncologist members of the Kyoto Radiation Oncology Study Group (KROSG)

International Nuclear Information System (INIS)

Mampuya, Wambaka Ange; Matsuo, Yukinori; Nakamura, Akira; Hiraoka, Masahiro

2017-01-01

This study aimed to evaluate the self-reported prevalence of burnout and psychological morbidity among radiation oncologists members of the Kyoto Radiation Oncology Study Group (KROSG) and to identify factors contributing to burnout. We mailed an anonymous survey to 125 radiation oncologists members of the KROSG. The survey included; the demographic data, the Maslach Burnout Inventory – Human Services Survey (MBI-HSS) and the 12-item General Health Questionnaire (GHQ-12). There were 87 responses out of 125 eligible respondents (69.6% response rate). In terms of burnout, three participants (3.4%) fulfilled the MBI-HSS criteria of having simultaneously high emotional exhaustion (EE), high depersonalization (DP) and low sense of personal accomplishment (PA). Eighteen (20.6%) reported a high score for either EE or DP meeting the alternative criteria for burnout with three of these simultaneously having high EE and high DP. The prevalence of psychological morbidity estimated using GHQ-12 was 32%. A high level of EE and low level of PA significantly correlated with high level of psychological morbidity with P < 0.001 and <0.01 respectively. Having palliative care activities other than radiotherapy and number of patients treated per year were the only factors associated with burnout. This is the first study investigating the prevalence of burnout and psychological morbidity among radiation oncologists in Japan. Compared with other studies involving radiation oncologists, the prevalence of low personal accomplishment was particularly high in the present study. The prevalence of psychological morbidity was almost the double that of the Japanese general population and was significantly associated with low PA and high EE.

JS-K promotes apoptosis by inducing ROS production in human prostate cancer cells.

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Qiu, Mingning; Chen, Lieqian; Tan, Guobin; Ke, Longzhi; Zhang, Sai; Chen, Hege; Liu, Jianjun

2017-03-01

Reactive oxygen species (ROS) are chemical species that alter redox status, and are responsible for inducing carcinogenesis. The purpose of the present study was to assess the effects of the glutathione S transferase-activated nitric oxide donor prodrug, JS-K, on ROS accumulation and on proliferation and apoptosis in human prostate cancer cells. Cell proliferation and apoptosis, ROS accumulation and the activation of the mitochondrial signaling pathway were measured. The results demonstrated that JS-K may inhibit prostate cancer cell growth in a dose- and time-dependent manner, and induce ROS accumulation and apoptosis in a dose-dependent manner. With increasing concentrations of JS-K, expression of pro-apoptotic proteins increased, but Bcl-2 expression decreased. Additionally, the antioxidant N-acetylcysteine reversed JS-K-induced cell apoptosis; conversely, the pro-oxidant glutathione disulfide exacerbated JS-K-induced apoptosis. In conclusion, the data suggest that JS-K induces prostate cancer cell apoptosis by increasing ROS levels.

Elucidating hormonal/ROS networks during seed germination: insights and perspectives

DEFF Research Database (Denmark)

Diaz-Vivancos, Pedro; Barba Espin, Gregorio; Hernández, José Antonio

2013-01-01

” technologies together with physiological and biochemical approaches have revealed that seed germination is a very complex process that depends on multiple biochemical and molecular variables. The pivotal role of phytohormones in promoting germination now appears to be interdependent with ROS metabolism......While authors have traditionally emphasized the deleterious effects of reactive oxygen species (ROS) on seed biology, their role as signaling molecules during seed dormancy alleviation and germination is now the focus of many studies around the world. Over the last few years, studies using “-omics......, involving mitogen-activated protein kinase cascade activation, gene expression and post-translational protein modifications. This review is, thus, an attempt to summarize the new discoveries involving ROS and seed germination. The study of these interactions may supply markers of seed quality that might...

Perspectives of medical oncologists regarding music therapy for patients with cancer in Turkey - can musicology be integrated into psycho-oncology?

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Tanriverdi, Ozgur; Aydemir, Nil Fatma

2014-01-01

Music therapy is a common complementary and alternative therapy in addition to medical treatment for patients with cancer. If music therapy, which is known has a positive effect on human emotions and behaviors, is a useful additional therapy, it should be more integrated into pyscho-oncology. In this study, we aimed to determine medical oncologist attitudes to music therapy for patients with cancer and knowledge about musicology and music therapy in Turkey. This survey study included questions about participant attitudes and knowledge regarding music therapy as well as demographic characteristics. The population of the study were 402 physicians working in medical oncology in Turkey and the sample covered 112 participants in the the survey. For statistical analyses the chi-square test, Fischer exact test, and Mann-Whitney U analysis are applied. In our study the rate for medical oncologists who were interested in music therapy was 28% (n=112). Some 30% (n=34) of medical oncologists recommended music therapy for their patients and 55% (n=61) recommended music therapy to prevent anxiety in patients with cancer. In this study, for more harmony with patients and in order to ensure management of adverse effect, it was concluded that music therapy should be regrded as an additional therapy in oncology clinics.

A pedagogia do Rosário, conteúdo educativo da festa: estudo do potencial pedagógico contido na festa de Nossa Senhora do Rosário

OpenAIRE

Maria das Merces Bonfim Ambrosio

1989-01-01

Elaborado como dissertação de Mestrado em educação, "A Pedagogia do Rosário-caráter educativo da Festa", objetivou desvendar os conteúdos educativos presentes na Festa de Nossa Senhora do Rosário, em Sete Lagoas-MG. Através da participação nesses eventos, nos anos de 1981 e 1982 e de entrevistas com membros das guardas de Nossa Senhora do rosário naquela cidade- além de leitura orientada-foi possível traçar as linhas dessa pedagogia, presentes neste trabalho. Trata-se de uma manifestação cult...

Reactive oxygen species (ROS – a family of fate deciding molecules pivotal in constructive inflammation and wound healing

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N Bryan

2012-09-01

Full Text Available Wound healing requires a fine balance between the positive and deleterious effects of reactive oxygen species (ROS; a group of extremely potent molecules, rate limiting in successful tissue regeneration. A balanced ROS response will debride and disinfect a tissue and stimulate healthy tissue turnover; suppressed ROS will result in infection and an elevation in ROS will destroy otherwise healthy stromal tissue. Understanding and anticipating the ROS niche within a tissue will greatly enhance the potential to exogenously augment and manipulate healing.Tissue engineering solutions to augment successful healing and remodelling of wounded or diseased tissue rely on a controlled balance between the constructive and destructive capacity of the leukocyte secretome, including ROS.This review comprehensively considers leukocyte derived ROS in tissue repair with particular interest in surgical intervention with inclusion of a biomaterial. The article considers ROS fundamental chemistry, formation, stimulation and clearance before applying this to discuss the implications of ROS in healing tissue with and without a biomaterial. We also systematically discuss ROS in leukocyte signalling and compare and contrast experimental means of measuring ROS.

ROS evaluation for a series of CNTs and their derivatives using an ESR method with DMPO

International Nuclear Information System (INIS)

Tsuruoka, S; Noguchi, T; Endo, M; Tristan, F; Terrones, M; Takeuchi, K; Koyama, K; Usui, Y; Matsumoto, H; Saito, N; Porter, D W; Castranova, V

2013-01-01

Carbon nanotubes (CNTs) are important materials in advanced industries. It is a concern that pulmonary exposure to CNTs may induce carcinogenic responses. It has been recently reported that CNTs scavenge ROS though non-carbon fibers generate ROS. A comprehensive evaluation of ROS scavenging using various kinds of CNTs has not been demonstrated well. The present work specifically investigates ROS scavenging capabilities with a series of CNTs and their derivatives that were physically treated, and with the number of commercially available CNTs. CNT concentrations were controlled at 0.2 through 0.6 wt%. The ROS scavenging rate was measured by ESR with DMPO. Interestingly, the ROS scavenging rate was not only influenced by physical treatments, but was also dependent on individual manufacturing methods. Ratio of CNTs to DMPO/ hydrogen peroxide is a key parameter to obtain appropriate ROS quenching results for comparison of CNTs. The present results suggest that dangling bonds are not a sole factor for scavenging, and electron transfer on the CNT surface is not clearly determined to be the sole mechanism to explain ROS scavenging.

ROS evaluation for a series of CNTs and their derivatives using an ESR method with DMPO.

Science.gov (United States)

Tsuruoka, S; Takeuchi, K; Koyama, K; Noguchi, T; Endo, M; Tristan, F; Terrones, M; Matsumoto, H; Saito, N; Usui, Y; Porter, D W; Castranova, V

Carbon nanotubes (CNTs) are important materials in advanced industries. It is a concern that pulmonary exposure to CNTs may induce carcinogenic responses. It has been recently reported that CNTs scavenge ROS though non-carbon fibers generate ROS. A comprehensive evaluation of ROS scavenging using various kinds of CNTs has not been demonstrated well. The present work specifically investigates ROS scavenging capabilities with a series of CNTs and their derivatives that were physically treated, and with the number of commercially available CNTs. CNT concentrations were controlled at 0.2 through 0.6 wt%. The ROS scavenging rate was measured by ESR with DMPO. Interestingly, the ROS scavenging rate was not only influenced by physical treatments, but was also dependent on individual manufacturing methods. Ratio of CNTs to DMPO/ hydrogen peroxide is a key parameter to obtain appropriate ROS quenching results for comparison of CNTs. The present results suggest that dangling bonds are not a sole factor for scavenging, and electron transfer on the CNT surface is not clearly determined to be the sole mechanism to explain ROS scavenging.

A Prediction Model for ROS1-Rearranged Lung Adenocarcinomas based on Histologic Features

OpenAIRE

Zhou, Jianya; Zhao, Jing; Zheng, Jing; Kong, Mei; Sun, Ke; Wang, Bo; Chen, Xi; Ding, Wei; Zhou, Jianying

2016-01-01

Aims To identify the clinical and histological characteristics of ROS1-rearranged non-small-cell lung carcinomas (NSCLCs) and build a prediction model to prescreen suitable patients for molecular testing. Methods and Results We identified 27 cases of ROS1-rearranged lung adenocarcinomas in 1165 patients with NSCLCs confirmed by real-time PCR and FISH and performed univariate and multivariate analyses to identify predictive factors associated with ROS1 rearrangement and finally developed predi...

ROS accumulation by PEITC selectively kills ovarian cancer cells via UPR-mediated apoptosis

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Yoon-hee eHong

2015-07-01

Full Text Available Unfolded protein response (UPR is crucial for both survival and death of mammalian cells, which is regulated by reactive oxygen species (ROS and nutrient depletion. In this study, we demonstrated the effect of ROS-accumulation, induced by β-phenethyl isothiocyanate (PEITC, on UPR mediated apoptosis in ovarian cancer cells. We used ovarian cancer cell lines, PA-1 and SKOV-3, with different p53 status (wild- and null- type, respectively. PEITC caused increased ROS-accumulation and inhibited proliferation selectively in ovarian cancer cells, and glutathione (GSH depletion in SKOV-3. However, PEITC did not cause any effect in normal ovarian epithelial cells and peripheral blood mononuclear cells. After 48 h of PEITC treatment (5 µM, apoptotic cell death was shown to increase significantly in the ovarian cancer cells and not in the normal cells. The key regulator of UPR-mediated apoptosis, CHOP/GADD153 and ER resident chaperone BiP/GRP78 were parallely up-regulated with activation of two major sensors of the UPR (PERK and ATF-6 in PA-1; PERK, and IRE1α in SKOV-3 in response to ROS accumulation induced by PEITC (5 µM. ROS scavenger, N-acetyl-cysteine (NAC, attenuated the effect of PEITC on UPR signatures (P-PERK, IRE1α, CHOP/GADD153, and BiP/GRP78, suggesting the involvement of ROS in UPR-mediated apoptosis. Altogether, PEITC induces UPR-mediated apoptosis in ovarian cancer cells via accumulation of ROS in a cancer-specific manner.

River recreation experience opportunities in two recreation opportunity spectrum (ROS) classes

Science.gov (United States)

Duane C. Wollmuth; John H. Schomaker; Lawrence C. Merriam

1985-01-01

The Recreation Opportunity Spectrum (ROS) system is used by the USDA Forest Service and USDI Bureau of Land Management for inventorying, classifying, and managing wildlands for recreation. Different ROS classes from the Colorado and Arkansas Rivers in Colorado were compared, using visitor survey data collected in 1979 and 1981, to see if the different classes offered...

Projected requirements for radiation oncologists and trainees in Australia and New Zealand to 2007

International Nuclear Information System (INIS)

Morgan, G.; Wigg, D.; Childs, J.

2000-01-01

Workloads in radiation oncology facilities in Australia and New Zealand have been increasing steadily for many years and it is anticipated that this trend will continue. In the present paper the projected number of radiation oncologists required to meet this demand to the year 2007 are estimated, along with the number of trainees required. The estimates are based on data from regular surveys by the Royal Australian and New Zealand College of Radiologists (RANZCR) for the years 1988-97 (inclusive). From these surveys profiles of numbers, age and gender of specialists and trainees are documented together with increases from the training programme and losses from retirement. It is concluded that if the current trainee numbers are increased by 12 in Australia and two in New Zealand, there will be approximately 10 radiation oncologists per million of population by the year 2007. This number is considered appropriate vue the anticipated increase in demands and complexity of treatment. Because projections too far forward are unreliable, careful monitoring of progress is essential to obtain the appropriate balance between requirement and supply. Comparisons are made with other estimates of needs including the 1998 Australian Medical Workforce Advisory Committee (AMWAC) Report and the New Zealand Clinical Agency Workforce Project Report in 1997. Copyright (1999) Blackwell Science Pty Ltd

Mitochondria and Mitochondrial ROS in Cancer: Novel Targets for Anticancer Therapy.

Science.gov (United States)

Yang, Yuhui; Karakhanova, Svetlana; Hartwig, Werner; D'Haese, Jan G; Philippov, Pavel P; Werner, Jens; Bazhin, Alexandr V

2016-12-01

Mitochondria are indispensable for energy metabolism, apoptosis regulation, and cell signaling. Mitochondria in malignant cells differ structurally and functionally from those in normal cells and participate actively in metabolic reprogramming. Mitochondria in cancer cells are characterized by reactive oxygen species (ROS) overproduction, which promotes cancer development by inducing genomic instability, modifying gene expression, and participating in signaling pathways. Mitochondrial and nuclear DNA mutations caused by oxidative damage that impair the oxidative phosphorylation process will result in further mitochondrial ROS production, completing the "vicious cycle" between mitochondria, ROS, genomic instability, and cancer development. The multiple essential roles of mitochondria have been utilized for designing novel mitochondria-targeted anticancer agents. Selective drug delivery to mitochondria helps to increase specificity and reduce toxicity of these agents. In order to reduce mitochondrial ROS production, mitochondria-targeted antioxidants can specifically accumulate in mitochondria by affiliating to a lipophilic penetrating cation and prevent mitochondria from oxidative damage. In consistence with the oncogenic role of ROS, mitochondria-targeted antioxidants are found to be effective in cancer prevention and anticancer therapy. A better understanding of the role played by mitochondria in cancer development will help to reveal more therapeutic targets, and will help to increase the activity and selectivity of mitochondria-targeted anticancer drugs. In this review we summarized the impact of mitochondria on cancer and gave summary about the possibilities to target mitochondria for anticancer therapies. J. Cell. Physiol. 231: 2570-2581, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Assessment of a Standardized ROS Production Profile in Humans by Electron Paramagnetic Resonance

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Simona Mrakic-Sposta

2012-01-01

Full Text Available Despite the growing interest in the role of reactive oxygen species (ROS in health and disease, reliable quantitative noninvasive methods for the assessment of oxidative stress in humans are still lacking. EPR technique, coupled to a specific spin probe (CMH: 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine is here presented as the method of choice to gain a direct measurement of ROS in biological fluids and tissues. The study aimed at demonstrating that, differently from currently available “a posteriori” assays of ROS-induced damage by means of biomolecules (e.g., proteins and lipids spin-trapping EPR provides direct evidence of the “instantaneous” presence of radical species in the sample and, as signal areas are proportional to the number of excited electron spins, lead to absolute concentration levels. Using a recently developed bench top continuous wave system (e-scan EPR scanner, Bruker dealing with very low ROS concentration levels in small (50 μL samples, we successfully monitored rapid ROS production changes in peripheral blood of athletes after controlled exercise and sedentary subjects after antioxidant supplementation. The correlation between EPR results and data obtained by various enzymatic assays (e.g., protein carbonyls and thiobarbituric acid reactive substances was determined too. Synthetically, our method allows reliable, quick, noninvasive quantitative determination of ROS in human peripheral blood.

Unravelling how plants benefit from ROS and NO reactions, while resisting oxidative stress.

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Considine, Michael J; Sandalio, Luisa Maria; Foyer, Christine Helen

2015-09-01

Reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO), play crucial roles in the signal transduction pathways that regulate plant growth, development and defence responses, providing a nexus of reduction/oxidation (redox) control that impacts on nearly every aspect of plant biology. Here we summarize current knowledge and concepts that lay the foundations of a new vision for ROS/RNS functions – particularly through signalling hubs – for the next decade. Plants have mastered the art of redox control using ROS and RNS as secondary messengers to regulate a diverse range of protein functions through redox-based, post-translational modifications that act as regulators of molecular master-switches. Much current focus concerns the impact of this regulation on local and systemic signalling pathways, as well as understanding how such reactive molecules can be effectively used in the control of plant growth and stress responses. The spectre of oxidative stress still overshadows much of our current philosophy and understanding of ROS and RNS functions. While many questions remain to be addressed – for example regarding inter-organellar regulation and communication, the control of hypoxia and how ROS/RNS signalling is used in plant cells, not only to trigger acclimation responses but also to create molecular memories of stress – it is clear that ROS and RNS function as vital signals of living cells.

How Does a Shared Decision-Making (SDM) Intervention for Oncologists Affect Participation Style and Preference Matching in Patients with Breast and Colon Cancer?

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Bieber, Christiane; Nicolai, Jennifer; Gschwendtner, Kathrin; Müller, Nicole; Reuter, Katrin; Buchholz, Angela; Kallinowski, Birgit; Härter, Martin; Eich, Wolfgang

2018-06-01

The aims of this study are to assess patients' preferred and perceived decision-making roles and preference matching in a sample of German breast and colon cancer patients and to investigate how a shared decision-making (SDM) intervention for oncologists influences patients' preferred and perceived decision-making roles and the attainment of preference matches. This study is a post hoc analysis of a randomised controlled trial (RCT) on the effects of an SDM intervention. The SDM intervention was a 12-h SDM training program for physicians in combination with decision board use. For this study, we analysed a subgroup of 107 breast and colon cancer patients faced with serious treatment decisions who provided data on specific questionnaires with regard to their preferred and perceived decision-making roles (passive, SDM or active). Patients filled in questionnaires immediately following a decision-relevant consultation (t1) with their oncologist. Eleven of these patients' 27 treating oncologists had received the SDM intervention within the RCT. A majority of cancer patients (60%) preferred SDM. A match between preferred and perceived decision-making roles was reached for 72% of patients. The patients treated by SDM-trained physicians perceived greater autonomy in their decision making (p < 0.05) with more patients perceiving SDM or an active role, but their preference matching was not influenced. A SDM intervention for oncologists boosted patient autonomy but did not improve preference matching. This highlights the already well-known reluctance of physicians to engage in explicit role clarification. German Clinical Trials Register DRKS00000539; Funding Source: German Cancer Aid.

Artemisinin induces ROS-mediated caspase3 activation in ASTC-a-1 cells

Science.gov (United States)

Xiao, Feng-Lian; Chen, Tong-Sheng; Qu, Jun-Le; Liu, Cheng-Yi

2010-02-01

Artemisinin (ART), an antimalarial phytochemical from the sweet wormwood plant or a naturally occurring component of Artemisia annua, has been shown a potential anticancer activity by apoptotic pathways. In our report, cell counting kit (CCK-8) assay showed that treatment of human lung adenocarcinoma (ASTC-a-1) cells with ART effectively increase cell death by inducing apoptosis in a time- and dose-dependent fashion. Hoechst 33258 staining was used to detect apoptosis as well. Reactive oxygen species (ROS) generation was observed in cells exposed to ART at concentrations of 400 μM for 48 h. N-acetyl-L-cysteine (NAC), an oxygen radical scavenger, suppressed the rate of ROS generation and inhibited the ART-induced apoptosis. Moreover, AFC assay (Fluorometric assay for Caspase3 activity) showed that ROS was involved in ART-induced caspase3 acitvation. Taken together, our data indicate that ART induces ROS-mediated caspase3 activation in a time-and dose-dependent way in ASCT-a-1 cells.

ROS Are Required for Mouse Spermatogonial Stem Cell Self-Renewal

OpenAIRE

Morimoto, Hiroko; Iwata, Kazumi; Ogonuki, Narumi; Inoue, Kimiko; Ogura, Atsuo; Kanatsu-Shinohara, Mito; Morimoto, Takeshi; Yabe-Nishimura, Chihiro; Shinohara, Takashi

2013-01-01

Reactive oxygen species (ROS) generation is implicated in stem cell self-renewal in several tissues but is thought to be detrimental for spermatogenesis as well as spermatogonial stem cells (SSCs). Using cultured SSCs, we show that ROS are generated via the AKT and MEK signaling pathways under conditions where the growth factors glial cell line-derived neurotrophic factor and fibroblast growth factor 2 drive SSC self-renewal and, instead, stimulate self-renewal at physiological levels. SSCs d...

Variations in Oncologist Recommendations for Chemotherapy for Stage IV Lung Cancer: What Is the Role of Performance Status?

Science.gov (United States)

Tisnado, Diana; Malin, Jennifer; Kahn, Katherine; Landrum, Mary Beth; Fletcher, Robert; Klabunde, Carrie; Clauser, Steven; Rogers, Selwyn O; Keating, Nancy L

2016-07-01

Chemotherapy prolongs survival in patients with advanced non-small-cell lung cancer. However, few studies have included patients with poor performance status. This study examined rates of oncologists' recommendations for chemotherapy by patient performance status and symptoms and how physician characteristics influence chemotherapy recommendations. We surveyed medical oncologists involved in the care of a population-based cohort of patients with lung cancer from the CanCORS (Cancer Care Outcomes Research and Surveillance) study. Physicians were queried about their likelihood to recommend chemotherapy to patients with stage IV lung cancer with varying performance status (Eastern Cooperative Oncology Group performance status 0 [good] v 3 [poor]) and presence or absence of tumor-related pain. Repeated measures logistic regression was used to estimate the independent associations of patients' performance status and symptoms and physicians' demographic and practice characteristics with chemotherapy recommendations. Nearly all physicians (adjusted rate, 97% to 99%) recommended chemotherapy for patients with good performance status, and approximately half (adjusted rate, 38% to 53%) recommended chemotherapy for patients with poor performance status (P factors, physician and practice characteristics were less strongly associated with chemotherapy recommendations in adjusted analyses. Strong consensus among oncologists exists for chemotherapy in patients with advanced non-small-cell lung cancer and good performance status. However, the relatively high rate of chemotherapy recommendations for patients with poor performance status despite the unfavorable risk-benefit profile highlights the need for ongoing work to define high-value care in oncology and to implement and evaluate strategies to align incentives for such care. Copyright © 2016 by American Society of Clinical Oncology.

Current status of brachytherapy in Korea: a national survey of radiation oncologists.

Science.gov (United States)

Kim, Haeyoung; Kim, Joo Young; Kim, Juree; Park, Won; Kim, Young Seok; Kim, Hak Jae; Kim, Yong Bae

2016-07-01

The aim of the present study was to acquire information on brachytherapy resources in Korea through a national survey of radiation oncologists. Between October 2014 and January 2015, a questionnaire on the current status of brachytherapy was distributed to all 86 radiation oncology departments in Korea. The questionnaire was divided into sections querying general information on human resources, brachytherapy equipment, and suggestions for future directions of brachytherapy policy in Korea. The response rate of the survey was 88.3%. The average number of radiation oncologists per center was 2.3. At the time of survey, 28 centers (36.8%) provided brachytherapy to patients. Among the 28 brachytherapy centers, 15 (53.5%) were located in in the capital Seoul and its surrounding metropolitan areas. All brachytherapy centers had a high-dose rate system using (192)Ir (26 centers) or (60)Co (two centers). Among the 26 centers using (192)Ir sources, 11 treated fewer than 40 patients per year. In the two centers using (60)Co sources, the number of patients per year was 16 and 120, respectively. The most frequently cited difficulties in performing brachytherapy were cost related. A total of 21 centers had a plan to sustain the current brachytherapy system, and four centers noted plans to upgrade their brachytherapy system. Two centers stated that they were considering discontinuation of brachytherapy due to cost burdens of radioisotope source replacement. The present study illustrated the current status of brachytherapy in Korea. Financial difficulties were the major barriers to the practice of brachytherapy.

Particulate matter exposure exacerbates high glucose-induced cardiomyocyte dysfunction through ROS generation.

Directory of Open Access Journals (Sweden)

Li Zuo

Full Text Available Diabetes mellitus and fine particulate matter from diesel exhaust (DEP are both important contributors to the development of cardiovascular disease (CVD. Diabetes mellitus is a progressive disease with a high mortality rate in patients suffering from CVD, resulting in diabetic cardiomyopathy. Elevated DEP levels in the air are attributed to the development of various CVDs, presumably since fine DEP (<2.5 µm in diameter can be inhaled and gain access to the circulatory system. However, mechanisms defining how DEP affects diabetic or control cardiomyocyte function remain poorly understood. The purpose of the present study was to evaluate cardiomyocyte function and reactive oxygen species (ROS generation in isolated rat ventricular myocytes exposed overnight to fine DEP (0.1 µg/ml, and/or high glucose (HG, 25.5 mM. Our hypothesis was that DEP exposure exacerbates contractile dysfunction via ROS generation in cardiomyocytes exposed to HG. Ventricular myocytes were isolated from male adult Sprague-Dawley rats cultured overnight and sarcomeric contractile properties were evaluated, including: peak shortening normalized to baseline (PS, time-to-90% shortening (TPS(90, time-to-90% relengthening (TR(90 and maximal velocities of shortening/relengthening (±dL/dt, using an IonOptix field-stimulator system. ROS generation was determined using hydroethidine/ethidium confocal microscopy. We found that DEP exposure significantly increased TR(90, decreased PS and ±dL/dt, and enhanced intracellular ROS generation in myocytes exposed to HG. Further studies indicated that co-culture with antioxidants (0.25 mM Tiron and 0.5 mM N-Acetyl-L-cysteine completely restored contractile function in DEP, HG and HG+DEP-treated myocytes. ROS generation was blocked in HG-treated cells with mitochondrial inhibition, while ROS generation was blocked in DEP-treated cells with NADPH oxidase inhibition. Our results suggest that DEP exacerbates myocardial dysfunction in isolated

The endogenous nitric oxide mediates selenium-induced phytotoxicity by promoting ROS generation in Brassica rapa.

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Yi Chen

Full Text Available Selenium (Se is suggested as an emerging pollutant in agricultural environment because of the increasing anthropogenic release of Se, which in turn results in phytotoxicity. The most common consequence of Se-induced toxicity in plants is oxidative injury, but how Se induces reactive oxygen species (ROS burst remains unclear. In this work, histofluorescent staining was applied to monitor the dynamics of ROS and nitric oxide (NO in the root of Brassica rapa under Se(IV stress. Se(IV-induced faster accumulation of NO than ROS. Both NO and ROS accumulation were positively correlated with Se(IV-induced inhibition of root growth. The NO accumulation was nitrate reductase (NR- and nitric oxide synthase (NOS-dependent while ROS accumulation was NADPH oxidase-dependent. The removal of NO by NR inhibitor, NOS inhibitor, and NO scavenger could alleviate Se(IV-induced expression of Br_Rbohs coding for NADPH oxidase and the following ROS accumulation in roots, which further resulted in the amelioration of Se(IV-induced oxidative injury and growth inhibition. Thus, we proposed that the endogenous NO played a toxic role in B. rapa under Se(IV stress by triggering ROS burst. Such findings can be used to evaluate the toxic effects of Se contamination on crop plants.

Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS-driven DNA damage and apoptosis

Energy Technology Data Exchange (ETDEWEB)

Gundala, Sushma Reddy; Yang, Chunhua [Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Mukkavilli, Rao [Advinus Therapeutics, Karnataka (India); Paranjpe, Rutugandha; Brahmbhatt, Meera; Pannu, Vaishali; Cheng, Alice [Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Reid, Michelle D. [Department of Pathology, Emory University School of Medicine, Atlanta, GA (United States); Aneja, Ritu, E-mail: raneja@gsu.edu [Department of Biology, Georgia State University, Atlanta, GA 30303 (United States)

2014-10-01

Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, significantly inhibits growth and proliferation via ROS generation in human prostate cancer, PC-3 cells. HC perturbed cell-cycle kinetics and progression, reduced clonogenicity and mediated cytotoxicity by ROS-induced DNA damage leading to activation of several pro-apoptotic molecules. In addition, HC treatment elicited a novel autophagic response as evidenced by the appearance of acidic vesicular organelles and increased expression of autophagic markers, LC3-IIb and beclin-1. Interestingly, quenching of ROS with tiron, an antioxidant, offered significant protection against HC-induced inhibition of cell growth and down regulation of caspase-3, suggesting the crucial role of ROS in mediating cell death. The collapse of mitochondrial transmembrane potential by HC further revealed the link between ROS generation and induction of caspase-mediated apoptosis in PC-3 cells. Our data showed remarkable inhibition of prostate tumor xenografts by ∼ 72% upon daily oral administration of 150 mg/kg bw HC by quantitative tumor volume measurements and non-invasive real-time bioluminescent imaging. HC was well-tolerated at this dosing level without any observable toxicity. This is the first report to demonstrate the anti-prostate cancer efficacy of HC in vitro and in vivo, which is perhaps attributable to its selective prooxidant activity to eliminate cancer cells thus providing compelling grounds for future preclinical studies to validate its potential usefulness for prostate cancer management. - Highlights: • HC perturbs cell-cycle progression by induction of reactive oxygen species (ROS). • HC mediated cytotoxicity by ROS-induced DNA damage leading to

Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS-driven DNA damage and apoptosis

International Nuclear Information System (INIS)

Gundala, Sushma Reddy; Yang, Chunhua; Mukkavilli, Rao; Paranjpe, Rutugandha; Brahmbhatt, Meera; Pannu, Vaishali; Cheng, Alice; Reid, Michelle D.; Aneja, Ritu

2014-01-01

Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, significantly inhibits growth and proliferation via ROS generation in human prostate cancer, PC-3 cells. HC perturbed cell-cycle kinetics and progression, reduced clonogenicity and mediated cytotoxicity by ROS-induced DNA damage leading to activation of several pro-apoptotic molecules. In addition, HC treatment elicited a novel autophagic response as evidenced by the appearance of acidic vesicular organelles and increased expression of autophagic markers, LC3-IIb and beclin-1. Interestingly, quenching of ROS with tiron, an antioxidant, offered significant protection against HC-induced inhibition of cell growth and down regulation of caspase-3, suggesting the crucial role of ROS in mediating cell death. The collapse of mitochondrial transmembrane potential by HC further revealed the link between ROS generation and induction of caspase-mediated apoptosis in PC-3 cells. Our data showed remarkable inhibition of prostate tumor xenografts by ∼ 72% upon daily oral administration of 150 mg/kg bw HC by quantitative tumor volume measurements and non-invasive real-time bioluminescent imaging. HC was well-tolerated at this dosing level without any observable toxicity. This is the first report to demonstrate the anti-prostate cancer efficacy of HC in vitro and in vivo, which is perhaps attributable to its selective prooxidant activity to eliminate cancer cells thus providing compelling grounds for future preclinical studies to validate its potential usefulness for prostate cancer management. - Highlights: • HC perturbs cell-cycle progression by induction of reactive oxygen species (ROS). • HC mediated cytotoxicity by ROS-induced DNA damage leading to

SMG-1 kinase attenuates mitochondrial ROS production but not cell respiration deficits during hyperoxia.

Science.gov (United States)

Resseguie, Emily A; Brookes, Paul S; O'Reilly, Michael A

Supplemental oxygen (hyperoxia) used to treat individuals in respiratory distress causes cell injury by enhancing the production of toxic reactive oxygen species (ROS) and inhibiting mitochondrial respiration. The suppressor of morphogenesis of genitalia (SMG-1) kinase is activated during hyperoxia and promotes cell survival by phosphorylating the tumor suppressor p53 on serine 15. Here, we investigate whether SMG-1 and p53 blunt this vicious cycle of progressive ROS production and decline in mitochondrial respiration seen during hyperoxia. Human lung adenocarcinoma A549 and H1299 or colon carcinoma HCT116 cells were depleted of SMG-1, UPF-1, or p53 using RNA interference, and then exposed to room air (21% oxygen) or hyperoxia (95% oxygen). Immunoblotting was used to evaluate protein expression; a Seahorse Bioanalyzer was used to assess cellular respiration; and flow cytometry was used to evaluate fluorescence intensity of cells stained with mitochondrial or redox sensitive dyes. Hyperoxia increased mitochondrial and cytoplasmic ROS and suppressed mitochondrial respiration without changing mitochondrial mass or membrane potential. Depletion of SMG-1 or its cofactor, UPF1, significantly enhanced hyperoxia-induced mitochondrial but not cytosolic ROS abundance. They did not affect mitochondrial mass, membrane potential, or hyperoxia-induced deficits in mitochondrial respiration. Genetic depletion of p53 in A549 cells and ablation of the p53 gene in H1299 or HCT116 cells revealed that SMG-1 influences mitochondrial ROS through activation of p53. Our findings show that hyperoxia does not promote a vicious cycle of progressive mitochondrial ROS and dysfunction because SMG-1-p53 signaling attenuates production of mitochondrial ROS without preserving respiration. This suggests antioxidant therapies that blunt ROS production during hyperoxia may not suffice to restore cellular respiration.

ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

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Pierpaola Davalli

2016-01-01

Full Text Available The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS and/or Reactive Nitrosative Species (RNS. Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging.

Reactive oxygen species (ROS) and the heat stress response of Daphnia pulex: ROS-mediated activation of hypoxia-inducible factor 1 (HIF-1) and heat shock factor 1 (HSF-1) and the clustered expression of stress genes.

Science.gov (United States)

Klumpen, Eva; Hoffschröer, Nadine; Zeis, Bettina; Gigengack, Ulrike; Dohmen, Elias; Paul, Rüdiger J

2017-01-01

Heat stress in ectotherms involves direct (e.g. protein damage) and/or indirect effects (temperature-induced hypoxia and ROS formation), which cause activation of the transcription factors (TF) heat shock factor 1 (HSF-1) and/or hypoxia-inducible factor 1 (HIF-1). The present study focused on the links between stress (ROS) signals, nuclear (n) and cytoplasmic (c) HSF-1/HIF-1 levels, and stress gene expression on mRNA and protein levels (e.g. heat-shock protein 90, HSP90) upon acute heat and ROS (H 2 O 2 ) stress. Acute heat stress (30°C) evoked fluctuations in ROS level. Different feeding regimens, which affected the glutathione (GSH) level, allowed altering the frequency of ROS fluctuations. Other data showed fluctuation frequency to depend also on ROS production rate. The heat-induced slow or fast ROS fluctuations (at high or low GSH levels) evoked slow or fast fluctuations in the levels of nHIF-1α, nHSF-1 and gene products (mRNAs and protein), albeit after different time delays. Time delays to ROS fluctuations were, for example,shorter for nHIF-1α than for nHSF-1 fluctuations, and nHIF-1α fluctuations preceded and nHSF-1 fluctuations followed fluctuations in HSP90 mRNA level. Cytoplasmic TF levels either changed little (cHIF-1α) or showed a steady increase (cHSF-1). Applying acute H 2 O 2 stress (at 20°C) revealed effects on nHIF-1α and mRNA levels, but no significant effects on nHSF-1 level. Transcriptome data additionally showed coordinated fluctuations of mRNA levels upon acute heat stress, involving mRNAs for HSPs and other stress proteins, with all corresponding genes carrying DNA binding motifs for HIF-1 and HSF-1. This study provided evidence for promoting effects of ROS and HIF-1 on early haemoglobin, HIF-1α and HSP90 mRNA expressions upon heat or ROS stress. The increasing cHSF-1 level likely affected nHSF-1 level and later HSP90 mRNA expression. Heat stress evoked ROS fluctuations, with this stress signal forwarded via nHIF-1 and nHSF-1

UPP mediated Diabetic Retinopathy via ROS/PARP and NF-κB inflammatory factor pathways.

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Luo, D-W; Zheng, Z; Wang, H; Fan, Y; Chen, F; Sun, Y; Wang, W-J; Sun, T; Xu, X

2015-01-01

Diabetic retinopathy (DR) is a leading cause of blindness in adults at working age. Human diabetic retinopathy is characterized by the basement membrane thick, pericytes loss, microaneurysms formation, retina neovascularization and vitreous hemorrhage. To investigate whether UPP activated ROS/PARP and NF-κB inflammatory factor pathways in Diabetic Retinopathy, human retinal endothelial cells (HRECs) and rats with streptozotocin-induced diabetes were used to determine the effect of UPP on ROS generation, cell apoptosis, mitochondrial membrane potential (ΔΨm) and inflammatory factor protein expression, through flow cytometry assay, immunohistochemistry, Real-time PCR, Western blot analysis and ELISA. The levels of ROS and apoptosis and the expressions of UPP (Ub and E3) and inflammatory factor protein were increased in high glucose-induced HRECs and retina of diabetic rats, while ΔΨm was decreased. The UPP inhibitor and UbshRNA could attenuate these effects through inhibiting the pathway of ROS/PARP and the expression of NF-κB inflammatory factors, and the increased UPP was a result of high glucose-induced increase of ROS generation and NF-κBp65 expression, accompanied with the decrease of ΔΨm. Clinical study showed the overexpression of UPP and detachment of epiretinal membranes in proliferative DR (PDR) patients. It has been indicated that the pathogenic effect of UPP on DR was involved in the increase of ROS generation and NF-κB expression, which associated with the ROS/PARP and NF-κB inflammatory factor pathways. Our study supports a new insight for further application of UPP inhibitor in DR treatment.

European contribution to the study of ROS

DEFF Research Database (Denmark)

Egea, Javier; Fabregat, Isabel; Frapart, Yves M

2017-01-01

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better u...

A stochastic step model of replicative senescence explains ROS production rate in ageing cell populations.

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Conor Lawless

Full Text Available Increases in cellular Reactive Oxygen Species (ROS concentration with age have been observed repeatedly in mammalian tissues. Concomitant increases in the proportion of replicatively senescent cells in ageing mammalian tissues have also been observed. Populations of mitotic human fibroblasts cultured in vitro, undergoing transition from proliferation competence to replicative senescence are useful models of ageing human tissues. Similar exponential increases in ROS with age have been observed in this model system. Tracking individual cells in dividing populations is difficult, and so the vast majority of observations have been cross-sectional, at the population level, rather than longitudinal observations of individual cells.One possible explanation for these observations is an exponential increase in ROS in individual fibroblasts with time (e.g. resulting from a vicious cycle between cellular ROS and damage. However, we demonstrate an alternative, simple hypothesis, equally consistent with these observations which does not depend on any gradual increase in ROS concentration: the Stochastic Step Model of Replicative Senescence (SSMRS. We also demonstrate that, consistent with the SSMRS, neither proliferation-competent human fibroblasts of any age, nor populations of hTERT overexpressing human fibroblasts passaged beyond the Hayflick limit, display high ROS concentrations. We conclude that longitudinal studies of single cells and their lineages are now required for testing hypotheses about roles and mechanisms of ROS increase during replicative senescence.

A stochastic step model of replicative senescence explains ROS production rate in ageing cell populations.

Science.gov (United States)

Lawless, Conor; Jurk, Diana; Gillespie, Colin S; Shanley, Daryl; Saretzki, Gabriele; von Zglinicki, Thomas; Passos, João F

2012-01-01

Increases in cellular Reactive Oxygen Species (ROS) concentration with age have been observed repeatedly in mammalian tissues. Concomitant increases in the proportion of replicatively senescent cells in ageing mammalian tissues have also been observed. Populations of mitotic human fibroblasts cultured in vitro, undergoing transition from proliferation competence to replicative senescence are useful models of ageing human tissues. Similar exponential increases in ROS with age have been observed in this model system. Tracking individual cells in dividing populations is difficult, and so the vast majority of observations have been cross-sectional, at the population level, rather than longitudinal observations of individual cells.One possible explanation for these observations is an exponential increase in ROS in individual fibroblasts with time (e.g. resulting from a vicious cycle between cellular ROS and damage). However, we demonstrate an alternative, simple hypothesis, equally consistent with these observations which does not depend on any gradual increase in ROS concentration: the Stochastic Step Model of Replicative Senescence (SSMRS). We also demonstrate that, consistent with the SSMRS, neither proliferation-competent human fibroblasts of any age, nor populations of hTERT overexpressing human fibroblasts passaged beyond the Hayflick limit, display high ROS concentrations. We conclude that longitudinal studies of single cells and their lineages are now required for testing hypotheses about roles and mechanisms of ROS increase during replicative senescence.

The Affordance Template ROS Package for Robot Task Programming

Science.gov (United States)

Hart, Stephen; Dinh, Paul; Hambuchen, Kimberly

2015-01-01

This paper introduces the Affordance Template ROS package for quickly programming, adjusting, and executing robot applications in the ROS RViz environment. This package extends the capabilities of RViz interactive markers by allowing an operator to specify multiple end-effector waypoint locations and grasp poses in object-centric coordinate frames and to adjust these waypoints in order to meet the run-time demands of the task (specifically, object scale and location). The Affordance Template package stores task specifications in a robot-agnostic XML description format such that it is trivial to apply a template to a new robot. As such, the Affordance Template package provides a robot-generic ROS tool appropriate for building semi-autonomous, manipulation-based applications. Affordance Templates were developed by the NASA-JSC DARPA Robotics Challenge (DRC) team and have since successfully been deployed on multiple platforms including the NASA Valkyrie and Robonaut 2 humanoids, the University of Texas Dreamer robot and the Willow Garage PR2. In this paper, the specification and implementation of the affordance template package is introduced and demonstrated through examples for wheel (valve) turning, pick-and-place, and drill grasping, evincing its utility and flexibility for a wide variety of robot applications.

ROS Mediates Radiation-Induced Differentiation in Human Lung Fibroblast

International Nuclear Information System (INIS)

Park, Sa Rah; Ahn, Ji Yeon; Kim, Mi Hyeung; Lim, Min Jin; Yun, Yeon Sook; Song, Jie Young

2009-01-01

One of the most common tumors worldwide is lung cancer and the number of patients with lung cancer received radiotherapy is increasing rapidly. Although radiotherapy may have lots of advantages, it can also induce serious adverse effects such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of smooth muscle actin-alpha (a-SMA) and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-b), tumor necrosis factor (TNF), IL-6, platelet-derived growth factor (PDGF) and reactive oxygen species are related to fibrosis. It is also reported that reactive oxygen species (ROS) can be induced by radiation and can act as a second messenger in various signaling pathways. Therefore we focused on the role of ROS in radiation induced fibrosis. Here, we suggest that irradiation generate ROS mainly through NOX4, result in differentiation of lung fibroblast into myofibroblast

The oncologist as coordinator of the nutritional approach.

Science.gov (United States)

Bozzetti, Federico

2015-04-01

Although the nutritional approach, especially when delivered through a gastric or jejunal tube or in a central vein, is handled by the nutritional support team or a specialist in nutrition, it is the responsibility of the oncologist, who knows the natural history of the disease and the impact of the oncologic therapy, to identify the potential candidates for the nutritional support, to recommend the nutritional strategy and to integrate it within the oncologic program. If gastrointestinal function is preserved, the initial nutritional approach should be through oral supplementation, followed by tube feeding if previous attempts are unsuccessful or upper gastrointestinal tract is not accessible. Parenteral nutrition is the obligatory resort when patients are (sub)obstructed but it may also be a practical way to integrate an insufficient oral nutrient intake (so called "supplemental" parenteral nutrition). Depending on the patient's condition and the disease's stage, artificial nutrition may have a "permissive" role in patients receiving aggressive oncologic therapy or represent just a supportive treatment in patients likely to succumb from starvation sooner than from tumor progression. Copyright © 2015 Elsevier Inc. All rights reserved.

Variability Among Breast Radiation Oncologists in Delineation of the Postsurgical Lumpectomy Cavity

International Nuclear Information System (INIS)

Landis, Daniel M.; Luo Weixiu; Song Jun; Bellon, Jennifer R.; Punglia, Rinaa S.; Wong, Julia S.; Killoran, Joseph H.; Gelman, Rebecca; Harris, Jay R.

2007-01-01

Purpose: Partial breast irradiation (PBI) is becoming more widely used. Accurate determination of the surgical lumpectomy cavity volume is more critical with PBI than with whole breast radiation therapy. We examined the interobserver variability in delineation of the lumpectomy cavity among four academic radiation oncologists who specialize in the treatment of breast cancer. Methods and Materials: Thirty-four lumpectomy cavities in 33 consecutive patients were evaluated. Each physician contoured the cavity and a 1.5-cm margin was added to define the planning target volume (PTV). A cavity visualization score (CVS) was assigned (1-5). To eliminate bias, the physician of record was eliminated from the analysis in all cases. Three measures of variability of the PTV were developed: average shift of the center of mass (COM), average percent overlap between the PTV of two physicians (PVO), and standard deviation of the PTV. Results: Of variables examined, pathologic resection volume was significantly correlated with CVS, with larger volumes more easily visualized. Shift of the COM decreased and PVO increased significantly as CVS increased. For CVS 4 and 5 cases, the average COM shift was 3 mm and 2 mm, respectively, and PVO was 77% and 87%, respectively. In multiple linear regression, pathologic diameter >4 cm and CVS ≥3 were significantly associated with smaller COM shift. When CVS was omitted from analysis, PVO was significantly larger with pathologic diameter ≥5 cm, days to planning <36, and older age. Conclusions: Even among radiation oncologists who specialize in breast radiotherapy, there can be substantial differences in delineation of the postsurgical radiotherapy target volume. Large treatment margins may be prudent if the cavity is not clearly defined

Which benefits and harms of preoperative radiotherapy should be addressed? A Delphi consensus study among rectal cancer patients and radiation oncologists

International Nuclear Information System (INIS)

Kunneman, Marleen; Pieterse, Arwen H.; Stiggelbout, Anne M.; Marijnen, Corrie A.M.

2015-01-01

Background and purpose: We previously found considerable variation in information provision on preoperative radiotherapy (PRT) in rectal cancer. Our aims were to reach consensus among patients and oncologists on which benefits/harms of PRT should be addressed during the consultation, and to assess congruence with daily clinical practice. Materials and methods: A four-round Delphi-study was conducted with two expert panels: (1) 31 treated rectal cancer patients and (2) 35 radiation oncologists. Thirty-seven possible benefits/harms were shown. Participants indicated whether addressing the benefit/harm was (1) essential, (2) desired, (3) not necessary, or (4) to be avoided. Consensus was assumed when ⩾80% of the panel agreed. Results were compared to 81 audio-taped consultations. Results: The panels reached consensus that six topics should be addressed in all patients (local control, survival, long term altered defecation pattern and faecal incontinence, perineal wound healing problems, advice to avoid pregnancy), three in male patients (erectile dysfunction, ejaculation disorder, infertility), and four in female patients (vaginal dryness, pain during intercourse, menopause, infertility). On average, less than half of these topics were addressed in daily clinical practice. Conclusions: This study showed substantial overlap between benefits/harms that patients and oncologists consider important to address during the consultation, and at the same time poor congruence with daily clinical practice

Estrogen-induced DNA synthesis in vascular endothelial cells is mediated by ROS signaling

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Felty Quentin

2006-04-01

Full Text Available Abstract Background Since estrogen is known to increase vascular endothelial cell growth, elevated estrogen exposure from hormone replacement therapy or oral contraceptives has the potential to contribute in the development of abnormal proliferative vascular lesions and subsequent thickening of the vasculature. How estrogen may support or promote vascular lesions is not clear. We have examined in this study whether estrogen exposure to vascular endothelial cells increase the formation of reactive oxygen species (ROS, and estrogen-induced ROS is involved in the growth of endothelial cells. Methods The effect of estrogen on the production of intracellular oxidants and the role of estrogen-induced ROS on cell growth was studied in human umbilical vein endothelial cells. ROS were measured by monitoring the oxidation of 2'7'-dichlorofluorescin by spectrofluorometry. Endothelial cell growth was measured by a colorimetric immunoassay based on BrdU incorporation into DNA. Results Physiological concentrations of estrogen (367 fmol and 3.67 pmol triggered a rapid 2-fold increase in intracellular oxidants in endothelial cells. E2-induced ROS formation was inhibited to basal levels by cotreatment with the mitochondrial inhibitor rotenone (2 μM and xanthine oxidase inhibitor allopurinol (50 μM. Inhibitors of NAD(PH oxidase, apocynin and DPI, did not block E2-induced ROS formation. Furthermore, the NOS inhibitor, L-NAME, did not prevent the increase in E2-induced ROS. These findings indicate both mitochondria and xanthine oxidase are the source of ROS in estrogen treated vascular endothelial cells. E2 treated cells showed a 2-fold induction of BrdU incorporation at 18 h which was not observed in cells exposed to vehicle alone. Cotreatment with ebselen (20 μM and NAC (1 mM inhibited E2-induced BrdU incorporation without affecting the basal levels of DNA synthesis. The observed inhibitory effect of NAC and ebselen on E2-induced DNA synthesis was also shown

Characterization of structure and coagulation behaviour of refractory organic substances (ROS) using small-angle neutron scattering (SANS), small-angle x-ray scattering (SAXS) and x-ray microscopy; Charakterisierung von Struktur und Koagulationsverhalten von Refraktaeren Organischen Saeuren (ROS) mit Hilfe von Neutronenkleinwinkelstreuung (SANS), Roentgenkleinwinkelstreuung (SAXS) und Roentgenmikroskopie

Energy Technology Data Exchange (ETDEWEB)

Pranzas, P.K. [GKSS-Forschungszentrum Geesthacht GmbH (Germany). Inst. fuer Werkstofforschung

1999-07-01

In this work structure, coagulation and complexation behaviour of aquatic refractory organic substances (ROS) (humic and fulvic acids) were characterized. For this purpose a structural analytical system with the methods small-angle neutron scattering (SANS), small-angle x-ray scattering (SAXS) and X-ray microscopy with synchrotron radiation was developed and established. Size distributions of ROS of different origin were calculated from the scattering curves. Spherical ROS units were obtained, which coagulated by forming chainlike structures or disordered ROS agglomerates at higher concentrations. Additionally the average molecular weights of several ROS were calculated. Studies of the coagulation behaviour of ROS towards copper ions resulted in larger ROS-agglomerates besides the spherical ROS units. A linear relation between the addition of Cu{sup 2+} and the formation of the ROS-Cu{sup 2+}-agglomerates was found. With X-ray microscopy an extensive ROS-Cu{sup 2}-network structure could be registrated. For mercury and cadmium ions such coagulation interactions were not found. Investigations with X-ray microscopy of the coagulation behaviour of ROS towards the cationic surfactant DTB resulted in micel-like structures of equal size, which were spread throughout the solution. With increasing concentrations of DTB larger agglomerates up to network structures were obtained. (orig.) [German] In dieser Arbeit wurden Struktur, Koagulations- und Komplexierungsverhalten von aquatischen refraktaeren organischen Saeuren (ROS) (Humin- und Fulvinsaeuren) charakterisiert. Zu diesem Zweck wurde ein strukturanalytisches Gesamtsystem mit den Methoden Neutronenkleinwinkelstreuung (SANS), Roentgenkleinwinkelstreuung (SAXS) und Roentgenmikroskopie mit Synchrotronstrahlung entwickelt und etabliert. Fuer ROS unterschiedlicher Herkunft in Loesung wurden Groessenverteilungen aus den Streukurven berechnet. Es wurden kugelfoermige ROS-Einheiten gefunden, die bei hoeheren ROS

Detection of ROS1 Gene Rearrangement in Lung Adenocarcinoma: Comparison of IHC, FISH and Real-Time RT-PCR

OpenAIRE

Shan, Ling; Lian, Fang; Guo, Lei; Qiu, Tian; Ling, Yun; Ying, Jianming; Lin, Dongmei

2015-01-01

Aims To compare fluorescence in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative real-time reverse transcription-PCR (qRT-PCR) assays for detection of ROS1 fusion in a large number of ROS1-positive lung adenocatcinoma (ADC) patients. Methods Using IHC analysis, sixty lung ADCs including 16 cases with ROS1 protein expression and 44 cases without ROS1 expression were selected for this study. The ROS1 fusion status was examined by FISH and qRT-PCR assay. Results Among 60 ca...

DspA/E contributes to apoplastic accumulation of ROS in nonhost A. thaliana

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Alban eLaunay

2016-04-01

Full Text Available The bacterium Erwinia amylovora is responsible for the fire blight disease of Maleae, which provokes necrotic symptoms on aerial parts. The pathogenicity of this bacterium in hosts relies on its type three-secretion system (T3SS, a molecular syringe that allows the bacterium to inject effectors into the plant cell. E. amylovora-triggered disease in host plants is associated with the T3SS-dependent production of reactive oxygen species (ROS, although ROS are generally associated with resistance in other pathosystems. We showed previously that E. amylovora can multiply transiently in the nonhost plant Arabidopsis thaliana and that a T3SS-dependent production of intracellular ROS occurs during this interaction. In the present work we characterize the localization and source of hydrogen peroxide accumulation following E. amylovora infection. Transmission electron microscope (TEM analysis of infected tissues showed that hydrogen peroxide accumulation occurs in the cytosol, plastids, peroxisomes, and mitochondria as well as in the apoplast. Furthermore, TEM analysis showed that an E. amylovora dspA/E-deficient strain does not induce hydrogen peroxide accumulation in the apoplast. Consistently, a transgenic line expressing DspA/E accumulated ROS in the apoplast. The NADPH oxidase-deficient rbohD mutant showed a very strong reduction in hydrogen peroxide accumulation in response to E. amylovora inoculation. However, we did not find an increase in bacterial titers of E. amylovora in the rbohD mutant and the rbohD mutation did not suppress the toxicity of DspA/E when introgressed into a DspA/E-expressing transgenic line. Co-inoculation of E. amylovora with cycloheximide (CHX, which we found previously to suppress callose deposition and allow strong multiplication of E. amylovora in A. thaliana leaves, led to a strong reduction of apoplastic ROS accumulation but did not affect intracellular ROS. Our data strongly suggest that apoplastic ROS accumulation is

micROS: a morphable, intelligent and collective robot operating system.

Science.gov (United States)

Yang, Xuejun; Dai, Huadong; Yi, Xiaodong; Wang, Yanzhen; Yang, Shaowu; Zhang, Bo; Wang, Zhiyuan; Zhou, Yun; Peng, Xuefeng

2016-01-01

Robots are developing in much the same way that personal computers did 40 years ago, and robot operating system is the critical basis. Current robot software is mainly designed for individual robots. We present in this paper the design of micROS, a morphable, intelligent and collective robot operating system for future collective and collaborative robots. We first present the architecture of micROS, including the distributed architecture for collective robot system as a whole and the layered architecture for every single node. We then present the design of autonomous behavior management based on the observe-orient-decide-act cognitive behavior model and the design of collective intelligence including collective perception, collective cognition, collective game and collective dynamics. We also give the design of morphable resource management, which first categorizes robot resources into physical, information, cognitive and social domains, and then achieve morphability based on self-adaptive software technology. We finally deploy micROS on NuBot football robots and achieve significant improvement in real-time performance.

ROS-TMS and Big Sensor Box: Platforms for Informationally Structured Environment

OpenAIRE

倉爪, 亮; ユンソク, ピョ; 辻, 徳生; 河村, 晃宏

2017-01-01

This paper proposes new software and hardware platforms for an informationally structured environment named ROS-TMS and Big Sensor Box. We started the development of a management system for an informationally structured environment named TMS (Town Management System) in Robot Town Project in 2005. Since then we are continuing our efforts for the improvement of the performance and the enhancement of the functions of the TMS. Recently, we launched a new version of TMS named ROS-TMS, which resolv...

Development of an in vitro photosafety evaluation method utilizing intracellular ROS production in THP-1 cells.

Science.gov (United States)

Toyoda, Akemi; Itagaki, Hiroshi

2018-01-01

Photoreactive compounds that may experience exposure to ultraviolet (UV) radiation can lead to the intracellular production of reactive oxygen species (ROS), which may cause phototoxic and photoallergenic responses. Here, we developed a novel in vitro photosafety assay and investigated whether it could be used to predict phototoxicity and photosensitivity by measuring changes in intracellular ROS production. THP-1 cells that had previously taken up 5-(and-6)-carboxy-2',7'-difluorodihydrofluorescein diacetate (carboxy-H 2 DFFDA), a ROS-sensitive fluorescent reagent, were exposed to photoreactive substances such as phototoxic and photoallergenic materials and then subjected to with UV-A irradiation (5 J/cm 2 ). The fluorescence intensity was subsequently measured using a flow cytometer, and the intracellular ROS production was calculated. A statistically significant increase in ROS following treatment with photoreactive substances was observed in cells irradiated with UV-A. In contrast, no significant increase was observed for non-photoreactive substances in comparison to the control solution. Next, to confirm the impact of intracellular ROS on the photosensitive response, changes in CD86 and CD54 expression were measured following quencher addition during the photo human cell line activation test (photo h-CLAT). The results confirmed the reduction of CD86 and CD54 expression in response to photoallergenic substances following quencher addition. Together, these findings suggest that intracellular ROS production is involved in photosensitizing reactions. Therefore, we suggest that the developed method utilizing intracellular ROS production as an index may be useful as a novel in vitro evaluation tool for photoreactive substances.

Endogenous cytokinin overproduction modulates ROS homeostasis and decreases salt stress resistance in Arabidopsis thaliana

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Yanping eWang

2015-11-01

Full Text Available Cytokinins in plants are crucial for numerous biological processes, including seed germination, cell division and differentiation, floral initiation and adaptation to abiotic stresses. The salt stress can promote reactive oxygen species (ROS production in plants which are highly toxic and ultimately results in oxidative stress. However, the correlation between endogenous cytokinin production and ROS homeostasis in responding to salt stress is poorly understood. In this study, we analyzed the correlation of overexpressing the cytokinin biosynthetic gene AtIPT8 (adenosine phosphate-isopentenyl transferase 8 and the response of salt stress in Arabidopsis. Overproduction of cytokinins, which was resulted by the inducible overexpression of AtIPT8, significantly inhibited the primary root growth and true leaf emergence, especially under the conditions of exogenous salt, glucose and mannitol treatments. Upon cytokinin overproduction, the salt stress resistance was declined, and resulted in less survival rates and chlorophyll content. Interestingly, ROS production was obviously increased with the salt treatment, accompanied by endogenously overproduced cytokinins. The activities of CAT and SOD, which are responsible for scavenging ROS, were also affected. Transcription profiling revealed that the differential expressions of ROS-producing and scavenging related genes, the photosynthesis-related genes and stress responsive genes were existed in transgenic plants of overproducing cytokinins. Our results suggested that broken in the homeostasis of cytokinins in plant cells could modulate the salt stress responses through a ROS-mediated regulation in Arabidopsis.

Intracellular ROS protection efficiency and free radical-scavenging activity of curcumin.

Directory of Open Access Journals (Sweden)

Abolfazl Barzegar

Full Text Available Curcumin has many pharmaceutical applications, many of which arise from its potent antioxidant properties. The present research examined the antioxidant activities of curcumin in polar solvents by a comparative study using ESR, reduction of ferric iron in aqueous medium and intracellular ROS/toxicity assays. ESR data indicated that the steric hindrance among adjacent big size groups within a galvinoxyl molecule limited the curcumin to scavenge galvinoxyl radicals effectively, while curcumin showed a powerful capacity for scavenging intracellular smaller oxidative molecules such as H₂O₂, HO•, ROO•. Cell viability and ROS assays demonstrated that curcumin was able to penetrate into the polar medium inside the cells and to protect them against the highly toxic and lethal effects of cumene hydroperoxide. Curcumin also showed good electron-transfer capability, with greater activity than trolox in aqueous solution. Curcumin can readily transfer electron or easily donate H-atom from two phenolic sites to scavenge free radicals. The excellent electron transfer capability of curcumin is because of its unique structure and different functional groups, including a β-diketone and several π electrons that have the capacity to conjugate between two phenyl rings. Therfore, since curcumin is inherently a lipophilic compound, because of its superb intracellular ROS scavenging activity, it can be used as an effective antioxidant for ROS protection within the polar cytoplasm.

The role of 12/15-lipoxygenases in ROS-mediated neuronal cell death

OpenAIRE

Tobaben, Svenja

2011-01-01

Oxidative stress has been established as a key trigger of neuronal dysfunction and death in age-related neurodegenerative diseases and in delayed neuronal death after acute brain injury by ischemic stroke or brain trauma. Despite increasing knowledge on the toxicity of reactive oxygen species (ROS) and oxidized reaction products that may further accelerate neuronal cell death, the major sources of ROS formation and the mechanisms ...

ROS generation and multiple forms of mammalian mitochondrial glycerol-3-phosphate dehydrogenase

Czech Academy of Sciences Publication Activity Database

Mráček, Tomáš; Holzerová, Eliška; Drahota, Zdeněk; Kovářová, Nikola; Vrbacký, Marek; Ješina, Pavel; Houštěk, Josef

2014-01-01

Roč. 1837, č. 1 (2014), s. 98-111 ISSN 0005-2728 R&D Projects: GA ČR(CZ) GPP303/10/P227; GA MŠk(CZ) LL1204 Grant - others:Univerzita Karlova(CZ) 750213 Institutional support: RVO:67985823 Keywords : mitochondrial glycerol-3-phosphate dehydrogenase * ROS production * supercomplex * in-gel ROS detection Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.353, year: 2014

Effects of quantum dots on the ROS amount of liver cancer stem cells.

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Li, Kunmeng; Xia, Chunhui; Wang, Baiqi; Chen, Hetao; Wang, Tong; He, Qian; Cao, Hailong; Wang, Yu

2017-07-01

Liver cancer (LC) is a serious disease that threatens human lives. LC has a high recurrence rate and poor prognosis. LC stem cells (LCSCs) play critical roles in these processes. However, the mechanism remains unclear. Reactive oxygen species (ROS) can be used to determine cell apoptosis and proliferation. However, studies of the effects of exogenous nanomaterials on LCSC ROS changes are rarely reported. In this work, quantum dots (QDs) were prepared using a hydrothermal method, and QDs were further modified with polyethylene glycol (PEG) and bovine serum albumin (BSA) using a chemical approach. The effects of QDs, PEG-modified QDs (PEG@QDs) and BSA-modified QDs (BSA@QDs) on the amounts of ROS in liver cancer PLC/PRF/5 (PLC) cells and liver cancer stem cells (LCSCs) were principally investigated. The results showed that when the concentration of QDs, PEG@QDs, and BSA@QDs were 10nM and 90nM, the ROS amount in PLC cells increased by approximately 2- to 5-fold. However, when the concentrations of these nanomaterials were 10nM and 90nM, ROS levels in LCSCs were reduced by approximately 50%. This critical path potentially leads to drug resistance and recurrence of LC. This work provides an important indication for further study of LC drug resistance and recurrence. Copyright © 2017 Elsevier B.V. All rights reserved.

Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

Energy Technology Data Exchange (ETDEWEB)

Jeong, Seung Min, E-mail: smjeong@catholic.ac.kr [Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Hwang, Sunsook; Seong, Rho Hyun [School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742 (Korea, Republic of)

2016-03-11

The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. - Highlights: • Pancreatic ductal adenocarcinoma (PDAC) exhibits an elevated transferrin receptor (TfR1) expression in comparison with non-transformed pancreatic cells. • TfR1 is required for PDAC growth by regulating mitochondrial respiration and ROS production. • TfR1 functions as a determinant of cell viability to oxidative stress in PDAC cells.

Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

International Nuclear Information System (INIS)

Jeong, Seung Min; Hwang, Sunsook; Seong, Rho Hyun

2016-01-01

The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. - Highlights: • Pancreatic ductal adenocarcinoma (PDAC) exhibits an elevated transferrin receptor (TfR1) expression in comparison with non-transformed pancreatic cells. • TfR1 is required for PDAC growth by regulating mitochondrial respiration and ROS production. • TfR1 functions as a determinant of cell viability to oxidative stress in PDAC cells.

Šiuolaikinės architektūros orientyrai: ikoniški pastatai hierarchinės klasifikacijos sistemoje

Directory of Open Access Journals (Sweden)

Almantas Bružas

2011-06-01

Full Text Available Architektūros orientyrai dažnai aptariami bendrai su gamtinės aplinkos elementais ir nenagrinėjami atsietai. Tačiau pastarųjų metų miestų vystymo tendencijos, nuolat didėjantis antropogeninių orientyrų skaičius miestovaizdyje bei auganti jų svarba reikalauja atidesnio požiūrio į šiuos miestų urbanistinės struktūros elementus. Straipsnyje aptariamas ikoniškų pastatų fenomenas bei kiti šiuolaikiniai architektūros orientyrai – aplinkoje savo fizinėmis bei estetinėmis savybėmis išsiskiriantys pastatai, urbanistiniai elementai bei šių kompleksai. Atsižvelgiant į pastarųjų metų miestų raidos kryptis bei urbanizuotos erdvės suvokimo sampratos pokyčius, siūloma šiuolaikinės architektūros orientyrus skirstyti į ikoniškos architektūros, erdvinės struktūros dominančių ir išsiskiriančių ženklų hierarchinius tipus. Aptariamos skirtingų tipų architektūros orientyrų skiriamosios savybės.Straipsnis lietuvių kalba

Development of an in vitro skin sensitization test based on ROS production in THP-1 cells.

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Saito, Kazutoshi; Miyazawa, Masaaki; Nukada, Yuko; Sakaguchi, Hitoshi; Nishiyama, Naohiro

2013-03-01

Recently, it has been reported that reactive oxygen species (ROS) produced by contact allergens can affect dendritic cell migration and contact hypersensitivity. The aim of the present study was to develop a new in vitro assay that could predict the skin sensitizing potential of chemicals by measuring ROS production in THP-1 (human monocytic leukemia cell line) cells. THP-1 cells were pre-loaded with a ROS sensitive fluorescent dye, 5-(and 6-)-chloromethyl-2', 7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA), for 15min, then incubated with test chemicals for 30min. The fluorescence intensity was measured by flow cytometry. For the skin sensitizers, 25 out of 30 induced over a 2-fold ROS production at more than 90% of cell viability. In contrast, increases were only seen in 4 out of 20 non-sensitizers. The overall accuracy for the local lymph node assay (LLNA) was 82% for 50 chemicals tested. A correlation was found between the estimated concentration showing 2-fold ROS production in the ROS assay and the EC3 values (estimated concentration required to induce positive response) of the LLNA. These results indicated that the THP-1 cell-based ROS assay was a rapid and highly sensitive detection system able to predict skin sensitizing potentials and potency of chemicals. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hyperthermia enhances radiosensitivity of colorectal cancer cells through ROS inducing autophagic cell death.

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Ba, Ming-Chen; Long, Hui; Wang, Shuai; Wu, Yin-Bing; Zhang, Bo-Huo; Yan, Zhao-Fei; Yu, Fei-Hong; Cui, Shu-Zhong

2018-04-01

Hyperthermia (HT) enhances the anti-cancer effects of radiotherapy (RT), but the precise biochemical mechanisms involved are unclear. This study was aim to investigate if mild HT sensitizes colorectal cancer cells to RT through reactive oxygen species (ROS)-inducing autophagic cell death in a mice model of HCT116 human colorectal cancer. HCT116 mice model were randomly divided into five groups: mock group, hyperthermia group (HT), radiotherapy group (RT), HT + RT group, and HT + RT +N-acetyl L-cysteine (NAC) group (HT + CT + NAC). After four weeks of treatment, cancer growth inhibition, rate and mitochondrial membrane potential were measured with MTT and JC-1 assays, respectively, while ROS were estimated fluorimetrically. The relationship of these parameters to expressions of autophagy-related genes Beclin1, LC3B, and mTOR was analyzed. Gene expression was measured by Real-Time polymerase chain reaction (RT-PCR). There were significant increases in ROS levels and mitochondrial membrane potential in the HT + RT group. ROS levels in the HT + RT group increased more significantly than in any other group. In contrast, ROS levels in the HT + RT + NAC group were significantly decreased relative to the HT + RT group. The number of autophagic bodies in HT + RT group was higher than that of mock group. There were significant increases in the expression of Beclin1 and LC3B genes, while mTOR expression was significantly decreased in the HT + CT group. Treatment with NAC reversed the pattern of these changes. These results indicate that HT enhances the radiosensitivity of colorectal cancer cells to RT through ROS inducing autophagic cell death. © 2017 Wiley Periodicals, Inc.

Is Whole-Exome Sequencing an Ethically Disruptive Technology? Perspectives of Pediatric Oncologists and Parents of Pediatric Patients With Solid Tumors.

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McCullough, Laurence B; Slashinski, Melody J; McGuire, Amy L; Street, Richard L; Eng, Christine M; Gibbs, Richard A; Parsons, D William; Plon, Sharon E

2016-03-01

It has been anticipated that physician and parents will be ill prepared or unprepared for the clinical introduction of genome sequencing, making it ethically disruptive. As a part of the Baylor Advancing Sequencing in Childhood Cancer Care study, we conducted semistructured interviews with 16 pediatric oncologists and 40 parents of pediatric patients with cancer prior to the return of sequencing results. We elicited expectations and attitudes concerning the impact of sequencing on clinical decision making, clinical utility, and treatment expectations from both groups. Using accepted methods of qualitative research to analyze interview transcripts, we completed a thematic analysis to provide inductive insights into their views of sequencing. Our major findings reveal that neither pediatric oncologists nor parents anticipate sequencing to be an ethically disruptive technology, because they expect to be prepared to integrate sequencing results into their existing approaches to learning and using new clinical information for care. Pediatric oncologists do not expect sequencing results to be more complex than other diagnostic information and plan simply to incorporate these data into their evidence-based approach to clinical practice, although they were concerned about impact on parents. For parents, there is an urgency to protect their child's health and in this context they expect genomic information to better prepare them to participate in decisions about their child's care. Our data do not support the concern that introducing genome sequencing into childhood cancer care will be ethically disruptive, that is, leave physicians or parents ill prepared or unprepared to make responsible decisions about patient care. © 2015 Wiley Periodicals, Inc.

Is Whole Exome Sequencing an Ethically Disruptive Technology? Perspectives of Pediatric Oncologists and Parents of Pediatric Patients with Solid Tumors

Science.gov (United States)

McCullough, Laurence B.; Slashinski, Melody J.; McGuire, Amy L.; Street, Richard L.; Eng, Christine M.; Gibbs, Richard A.; Parsons, D. Williams; Plon, Sharon E.

2016-01-01

Background Some anticipate that physician and parents will be ill-prepared or unprepared for the clinical introduction of genome sequencing, making it ethically disruptive. Procedure As part of the Baylor Advancing Sequencing in Childhood Cancer Care (BASIC3) study, we conducted semi-structured interviews with 16 pediatric oncologists and 40 parents of pediatric patients with cancer prior to the return of sequencing results. We elicited expectations and attitudes concerning the impact of sequencing on clinical decision-making, clinical utility, and treatment expectations from both groups. Using accepted methods of qualitative research to analyze interview transcripts, we completed a thematic analysis to provide inductive insights into their views of sequencing. Results Our major findings reveal that neither pediatric oncologists nor parents anticipate sequencing to be an ethically disruptive technology, because they expect to be prepared to integrate sequencing results into their existing approaches to learning and using new clinical information for care. Pediatric oncologists do not expect sequencing results to be more complex than other diagnostic information and plan simply to incorporate these data into their evidence-based approach to clinical practice although they were concerned about impact on parents. For parents, there is an urgency to protect their chil's health and in this context they expect genomic information to better prepare them to participate in decisions about their chil's care. Conclusion Our data do not support concern that introducing genome sequencing into childhood cancer care will be ethically disruptive, i.e., leave physicians or parents ill-prepared or unprepared to make responsible decisions about patient care. PMID:26505993

Serotonin-promoted elevation of ROS levels may lead to cardiac pathologies in diabetic rat

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Ali Tahir

2015-01-01

Full Text Available Patients with diabetes mellitus (DM develop tendencies toward heart disease. Hyperglycemia induces the release of serotonin from enterochromaffin cells (EC. Serotonin was observed to elevate reactive oxygen species (ROS and downregulate antioxidant enzymes. As a result, elevated levels of serotonin could contribute to diabetic complications, including cardiac hypertrophy. In the present study, diabetes mellitus was induced in rats by alloxan administration; this was followed by the administration of serotonin to experimental animals. ROS, catalase (CAT, superoxide dismutase (SOD, B-type natriuretic peptide (BNP expression, and histopathological assessments were performed. Elevated ROS concentrations and decreased antioxidant enzyme activities were detected. Further, we observed an increase in cell surface area and elevated BNP expression which suggests that events associated with cardiac hypertrophy were increased in serotonin-administered diabetic rats. We conclude that serotonin secretion in diabetes could contribute to diabetic complications, including cardiac hypertrophy, through enhanced ROS production.

NADPH oxidase AtrbohD and AtrbohF genes function in ROS-dependent ABA signaling in Arabidopsis

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Kwak, June M.; Mori, Izumi C.; Pei, Zhen-Ming; Leonhardt, Nathalie; Torres, Miguel Angel; Dangl, Jeffery L.; Bloom, Rachel E.; Bodde, Sara; Jones, Jonathan D.G.; Schroeder, Julian I.

2003-01-01

Reactive oxygen species (ROS) have been proposed to function as second messengers in abscisic acid (ABA) signaling in guard cells. However, the question whether ROS production is indeed required for ABA signal transduction in vivo has not yet been addressed, and the molecular mechanisms mediating ROS production during ABA signaling remain unknown. Here, we report identification of two partially redundant Arabidopsis guard cell-expressed NADPH oxidase catalytic subunit genes, AtrbohD and AtrbohF, in which gene disruption impairs ABA signaling. atrbohD/F double mutations impair ABA-induced stomatal closing, ABA promotion of ROS production, ABA-induced cytosolic Ca2+ increases and ABA- activation of plasma membrane Ca2+-permeable channels in guard cells. Exogenous H2O2 rescues both Ca2+ channel activation and stomatal closing in atrbohD/F. ABA inhibition of seed germination and root elongation are impaired in atrbohD/F, suggesting more general roles for ROS and NADPH oxidases in ABA signaling. These data provide direct molecular genetic and cell biological evidence that ROS are rate-limiting second messengers in ABA signaling, and that the AtrbohD and AtrbohF NADPH oxidases function in guard cell ABA signal transduction. PMID:12773379

BMP2 induces PANC-1 cell invasion by MMP-2 overexpression through ROS and ERK.

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Liu, Jun; Ben, Qi-Wen; Yao, Wei-Yan; Zhang, Jian-Jun; Chen, Da-Fan; He, Xiang-Yi; Li, Lei; Yuan, Yao-Zong

2012-06-01

The emerging roles of bone morphogenetic proteins (BMPs) in the initiation and progression of multiple cancers have drawn great attention in cancer research. We hypothesized that BMP2 promotes cancer metastasis by modulating MMP-2 secretion and activity through intracellular ROS regulation and ERK activation in human pancreatic cancer. Our data show that stimulation of PANC-1 cells with BMP2 induced MMP-2 secretion and activation, associated with decreased E-cadherin expression, resulting in epithelial-to-mesenchymal transformation (EMT) and cell invasion. Blockade of ROS by the ROS scavenger, 2-MPG, abolished cell invasion, inhibited the EMT process and decreased MMP-2 expression, suggesting ROS accumulation caused an increase in MMP-2 expression in BMP2-stimulated PANC-1 cell invasion. Furthermore, treatment of PANC-1 cells with 2-MPG or ERK inhibitor PD98059 reduced the phosphorylation of ERK, resulting in attenuation of BMP2-induced cell invasion and MMP-2 activation. Taken together, these results suggest that BMP2 induces the cell invasion of PANC-1 cells by enhancing MMP-2 secretion and acting through ROS accumulation and ERK activation.

Improving patient emotional functioning and psychological morbidity: evaluation of a consultation skills training program for oncologists.

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Girgis, Afaf; Cockburn, Jill; Butow, Phyllis; Bowman, Deborah; Schofield, Penelope; Stojanovski, Elizabeth; D'Este, Catherine; Tattersall, Martin H N; Doran, Christopher; Turner, Jane

2009-12-01

To evaluate whether a consultation skills training (CST) program with oncologists and trainees would improve skills in detecting and responding to patient distress, thereby improving their patients' emotional functioning and reducing psychological distress. Randomized-controlled trial with 29 medical and radiation oncologists from Australia randomized to CST group (n=15) or usual-care group (n=14). The CST consisted of a 1.5-day face-to-face workshop incorporating presentation of principles, a DVD modelling ideal behaviour and role-play practice, and four 1.5h monthly video-conferences. At the CST conclusion, patients of participating doctors were recruited (n=192 in CST group, n=183 in usual-care group), completing telephone surveys at baseline, 1 week and 3 months to assess quality of life, anxiety, depression and unmet psychosocial needs. Despite high patient functioning at baseline, anxiety significantly improved at 1-week follow-up in the CST group, compared to the control group. There were no statistically significant differences in emotional functioning, depression or unmet supportive care need between the groups. Consistent trends for greater improvements were observed in intervention compared to control group patients, suggesting the CST program deserves wider evaluation. Video-conferencing after a short training course may be an effective strategy for delivering CST.

Chelerythrine induced cell death through ROS-dependent ER stress in human prostate cancer cells

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Wu S

2018-05-01

Full Text Available Songjiang Wu, Yanying Yang, Feiping Li, Lifu Huang, Zihua Han, Guanfu Wang, Hongyuan Yu, Haiping Li Department of Urology, Enze Hospital of Taizhou Enze Medical Center (Group, Taizhou, China Introduction: Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer-related mortality worldwide and the third in USA in 2017. Chelerythrine (CHE, a naturalbenzo[c]phenanthridine alkaloid, formerly identified as a protein kinase C inhibitor, has also shown anticancer effect through a number of mechanisms. Herein, effect and mechanism of the CHE-induced apoptosis via reactive oxygen species (ROS-mediated endoplasmic reticulum (ER stress in prostate cancer cells were studied for the first time. Methods: In our present study, we investigated whether CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a dose-dependent manner in PC-3 cells. In addition, we showed that CHE increases intracellular ROS and leads to ROS-dependent ER stress and cell apoptosis. Results: Pre-treatment with N-acetyl cysteine, an ROS scavenger, totally reversed the CHE-induced cancer cell apoptosis as well as ER stress activation, suggesting that the ROS generation was responsible for the anticancer effects of CHE. Conclusion: Taken together, our findings support one of the anticancer mechanisms by which CHE increased ROS accumulation in prostate cancer cells, thereby leading to ER stress and caused intrinsic apoptotic signaling. The study reveals that CHE could be a potential candidate for application in the treatment of prostate cancer. Keywords: chelerythrine, reactive oxygen species, endoplasmic reticulum stress, apoptosis, prostate cancer

The 28. Congress of the Scientific Society of US radiologists and oncologists

International Nuclear Information System (INIS)

Pereslegin, I.A.; Zolotkov, A.G.

1987-01-01

Some reports of the 28th Congress of the Scientific Society of US Radiologists and Oncologists are reviewed. Promising effect of hyperthermia and irradiation in case of superficial tumors (recurrences and metastases of mammary gland carcinoma in thoracic wall) and limited potentialities in case of internal tumors are pointed out. A matter of interest is a series of reports on ten-year controlled clinical investigations and radiotherapy in comparison with radical mastectomy at early stages of mammary gland carcinoma. The reports contain information on application of principally new methods of X-ray, combined, complex and medicinal treatment of tumor of many localizations. Some radiotherapeutic methods were renewed, in particular, method of high dose interoperational irradiation

Spatio-temporal Model of Endogenous ROS and Raft-Dependent WNT/Beta-Catenin Signaling Driving Cell Fate Commitment in Human Neural Progenitor Cells

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Haack, Fiete; Lemcke, Heiko; Ewald, Roland; Rharass, Tareck; Uhrmacher, Adelinde M.

2015-01-01

Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it is also connected to a number of cancers and developmental disorders. Here we apply a combined in-vitro and in-silico approach to investigate the spatio-temporal regulation of WNT/β-catenin signaling during the early neural differentiation process of human neural progenitors cells (hNPCs), which form a new prospect for replacement therapies in the context of neurodegenerative diseases. Experimental measurements indicate a second signal mechanism, in addition to canonical WNT signaling, being involved in the regulation of nuclear β-catenin levels during the cell fate commitment phase of neural differentiation. We find that the biphasic activation of β-catenin signaling observed experimentally can only be explained through a model that combines Reactive Oxygen Species (ROS) and raft dependent WNT/β-catenin signaling. Accordingly after initiation of differentiation endogenous ROS activates DVL in a redox-dependent manner leading to a transient activation of down-stream β-catenin signaling, followed by continuous auto/paracrine WNT signaling, which crucially depends on lipid rafts. Our simulation studies further illustrate the elaborate spatio-temporal regulation of DVL, which, depending on its concentration and localization, may either act as direct inducer of the transient ROS/β-catenin signal or as amplifier during continuous auto-/parcrine WNT/β-catenin signaling. In addition we provide the first stochastic computational model of WNT/β-catenin signaling that combines membrane-related and intracellular processes, including lipid rafts/receptor dynamics as well as WNT- and ROS-dependent β-catenin activation. The model’s predictive ability is demonstrated under a wide range of varying conditions for in-vitro and in-silico reference data sets. Our in-silico approach is realized in a multi-level rule-based language, that facilitates the extension and modification of the

Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS-driven DNA damage and apoptosis

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Gundala, Sushma Reddy; Yang, Chunhua; Mukkavilli, Rao; Paranjpe, Rutugandha; Brahmbhatt, Meera; Pannu, Vaishali; Cheng, Alice; Reid, Michelle D.; Aneja, Ritu

2015-01-01

Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, significantly inhibits growth and proliferation via ROS generation in human prostate cancer, PC-3 cells. HC perturbed cell-cycle kinetics and progression, reduced clonogenicity and mediated cytotoxicity by ROS-induced DNA damage leading to activation of several pro-apoptotic molecules. In addition, HC treatment elicited a novel autophagic response as evidenced by the appearance of acidic vesicular organelles and increased expression of autophagic markers, LC3-IIb and beclin-1. Interestingly, quenching of ROS with tiron, an antioxidant, offered significant protection against HC-induced inhibition of cell growth and down regulation of caspase-3, suggesting the crucial role of ROS in mediating cell death. The collapse of mitochondrial transmembrane potential by HC further revealed the link between ROS generation and induction of caspase-mediated apoptosis in PC-3 cells. Our data showed remarkable inhibition of prostate tumor xenografts by ~72% upon daily oral administration of 150 mg/kg bw HC by quantitative tumor volume measurements and non-invasive real-time bioluminescent imaging. HC was well-tolerated at this dosing level without any observable toxicity. This is the first report to demonstrate the anti-prostate efficacy of HC in vitro and in vivo, which is perhaps attributable to its selective prooxidant activity to eliminate cancer cells thus providing compelling grounds for future preclinical studies to validate its potential usefulness for prostate cancer management. PMID:25064160

Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS-driven DNA damage and apoptosis.

Science.gov (United States)

Gundala, Sushma Reddy; Yang, Chunhua; Mukkavilli, Rao; Paranjpe, Rutugandha; Brahmbhatt, Meera; Pannu, Vaishali; Cheng, Alice; Reid, Michelle D; Aneja, Ritu

2014-10-01

Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, significantly inhibits growth and proliferation via ROS generation in human prostate cancer, PC-3 cells. HC perturbed cell-cycle kinetics and progression, reduced clonogenicity and mediated cytotoxicity by ROS-induced DNA damage leading to activation of several pro-apoptotic molecules. In addition, HC treatment elicited a novel autophagic response as evidenced by the appearance of acidic vesicular organelles and increased expression of autophagic markers, LC3-IIb and beclin-1. Interestingly, quenching of ROS with tiron, an antioxidant, offered significant protection against HC-induced inhibition of cell growth and down regulation of caspase-3, suggesting the crucial role of ROS in mediating cell death. The collapse of mitochondrial transmembrane potential by HC further revealed the link between ROS generation and induction of caspase-mediated apoptosis in PC-3 cells. Our data showed remarkable inhibition of prostate tumor xenografts by ~72% upon daily oral administration of 150mg/kg bw HC by quantitative tumor volume measurements and non-invasive real-time bioluminescent imaging. HC was well-tolerated at this dosing level without any observable toxicity. This is the first report to demonstrate the anti-prostate cancer efficacy of HC in vitro and in vivo, which is perhaps attributable to its selective prooxidant activity to eliminate cancer cells thus providing compelling grounds for future preclinical studies to validate its potential usefulness for prostate cancer management. Copyright © 2014 Elsevier Inc. All rights reserved.

ROS and RNS Signaling in Heart Disorders: Could Antioxidant Treatment Be Successful?

Directory of Open Access Journals (Sweden)

Igor Afanas'ev

2011-01-01

Full Text Available There is not too much success in the antioxidant treatment of heart deceases in humans. However a new approach is now developed that suggests that depending on their structures and concentrations antioxidants can exhibit much more complicated functions in many pathological disorders. It is now well established that physiological free radicals superoxide and nitric oxide together with their derivatives hydrogen peroxide and peroxynitrite (all are named reactive oxygen species (ROS and reactive nitrogen species (RNS play a more important role in heart diseases through their signaling functions. Correspondingly this work is dedicated to the consideration of damaging signaling by ROS and RNS in various heart and vascular disorders: heart failure (congestive heart failure or CHF, left ventricular hypertrophy (LVH, coronary heart disease, cardiac arrhythmias, and so forth. It will be demonstrated that ROS overproduction (oxidative stress is a main origin of the transformation of normal physiological signaling processes into the damaging ones. Furthermore the favorable effects of low/moderate oxidative stress through preconditioning mechanisms in ischemia/reperfusion will be considered. And in the last part we will discuss the possibility of efficient application of antioxidants and enzyme/gene inhibitors for the regulation of damaging ROS signaling in heart disorders.

The hormesis effect of plasma-elevated intracellular ROS on HaCaT cells

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Szili, Endre J.; Harding, Frances J.; Hong, Sung-Ha; Herrmann, Franziska; Voelcker, Nicolas H.; Short, Robert D.

2015-12-01

We have examined the link between ionized-gas plasma delivery of reactive oxygen species (ROS) to immortalized keratinocyte (HaCaT) cells and cell fate, defined in terms of cell viability versus death. Phospholipid vesicles were used as cell mimics to measure the possible intracellular ROS concentration, [ROSi], delivered by various plasma treatments. Cells were exposed to a helium cold atmospheric plasma (CAP) jet for different plasma exposure times (5-60 s) and gas flow rates (50-1000 ml min-1). Based upon the [ROSi] data we argue that plasma-generated ROS in the cell culture medium can readily diffuse into real cells. Plasma exposure that equated to an [ROSi] in the range of 3.81  ×  10-10-9.47  ×  10-8 M, measured at 1 h after the plasma exposure, resulted in increased cell viability at 72 h; whereas a higher [ROSi] at 1 h decreased cell viability after 72 h of culture. This may be because of the manner in which the ROS are delivered by the plasma: HaCaT cells better tolerate a low ROS flux over an extended plasma exposure period of 1 min, compared to a high flux delivered in a few seconds, although the final [ROSi] may be the same. Our results suggest that plasma stimulation of HaCaT cells follows the principle of hormesis.

Arabidopsis GRI is involved in the regulation of cell death induced by extracellular ROS.

Science.gov (United States)

Wrzaczek, Michael; Brosché, Mikael; Kollist, Hannes; Kangasjärvi, Jaakko

2009-03-31

Reactive oxygen species (ROS) have important functions in plant stress responses and development. In plants, ozone and pathogen infection induce an extracellular oxidative burst that is involved in the regulation of cell death. However, very little is known about how plants can perceive ROS and regulate the initiation and the containment of cell death. We have identified an Arabidopsis thaliana protein, GRIM REAPER (GRI), that is involved in the regulation of cell death induced by extracellular ROS. Plants with an insertion in GRI display an ozone-sensitive phenotype. GRI is an Arabidopsis ortholog of the tobacco flower-specific Stig1 gene. The GRI protein appears to be processed in leaves with a release of an N-terminal fragment of the protein. Infiltration of the N-terminal fragment of the GRI protein into leaves caused cell death in a superoxide- and salicylic acid-dependent manner. Analysis of the extracellular GRI protein yields information on how plants can initiate ROS-induced cell death during stress response and development.

Toward real-time regional earthquake simulation II: Real-time Online earthquake Simulation (ROS) of Taiwan earthquakes

Science.gov (United States)

Lee, Shiann-Jong; Liu, Qinya; Tromp, Jeroen; Komatitsch, Dimitri; Liang, Wen-Tzong; Huang, Bor-Shouh

2014-06-01

We developed a Real-time Online earthquake Simulation system (ROS) to simulate regional earthquakes in Taiwan. The ROS uses a centroid moment tensor solution of seismic events from a Real-time Moment Tensor monitoring system (RMT), which provides all the point source parameters including the event origin time, hypocentral location, moment magnitude and focal mechanism within 2 min after the occurrence of an earthquake. Then, all of the source parameters are automatically forwarded to the ROS to perform an earthquake simulation, which is based on a spectral-element method (SEM). A new island-wide, high resolution SEM mesh model is developed for the whole Taiwan in this study. We have improved SEM mesh quality by introducing a thin high-resolution mesh layer near the surface to accommodate steep and rapidly varying topography. The mesh for the shallow sedimentary basin is adjusted to reflect its complex geometry and sharp lateral velocity contrasts. The grid resolution at the surface is about 545 m, which is sufficient to resolve topography and tomography data for simulations accurate up to 1.0 Hz. The ROS is also an infrastructural service, making online earthquake simulation feasible. Users can conduct their own earthquake simulation by providing a set of source parameters through the ROS webpage. For visualization, a ShakeMovie and ShakeMap are produced during the simulation. The time needed for one event is roughly 3 min for a 70 s ground motion simulation. The ROS is operated online at the Institute of Earth Sciences, Academia Sinica (http://ros.earth.sinica.edu.tw/). Our long-term goal for the ROS system is to contribute to public earth science outreach and to realize seismic ground motion prediction in real-time.

Pre-treatment of soybean plants with calcium stimulates ROS responses and mitigates infection by Sclerotinia sclerotiorum.

Science.gov (United States)

Arfaoui, Arbia; El Hadrami, Abdelbasset; Daayf, Fouad

2018-01-01

Considering the high incidence of white mold caused by Sclerotinia sclerotiorum in a variety of field crops and vegetables, different control strategies are needed to keep the disease under economical threshold. This study assessed the effect of foliar application of a calcium formulation on disease symptoms, oxalic acid production, and on the oxidative stress metabolism in soybean plants inoculated with each of two isolates of the pathogen that have contrasting aggressiveness (HA, highly-aggressive versus WA, weakly-aggressive). Changes in reactive oxygen species (ROS) levels in soybean plants inoculated with S. sclerotiorum isolates were assessed at 6, 24, 48 and 72 h post inoculation (hpi). Generation of ROS including hydrogen peroxide (H 2 O 2 ), anion superoxide (O 2 - ) and hydroxyl radical (OH) was evaluated. Inoculation with the WA isolate resulted in more ROS accumulation compared to the HA isolate. Pre-treatment with the calcium formulation restored ROS production in plants inoculated with the HA isolate. We also noted a marked decrease in oxalic acid content in the leaves inoculated with the HA isolate in presence of calcium, which coincided with an increase in plant ROS production. The expression patterns of genes involved in ROS detoxification in response to the calcium treatments and/or inoculation with S. Sclerotiorum isolates were monitored by RT-qPCR. All of the tested genes showed a higher expression in response to inoculation with the WA isolate. The expression of most genes tested peaked at 6 hpi, which preceded ROS accumulation in the soybean leaves. Overall, these data suggest that foliar application of calcium contributes to a decrease in oxalic acid production and disease, arguably via modulation of the ROS metabolism. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Aluminium-induced excessive ROS causes cellular damage and metabolic shifts in black gram Vigna mungo (L.) Hepper.

Science.gov (United States)

Chowra, Umakanta; Yanase, Emiko; Koyama, Hiroyuki; Panda, Sanjib Kumar

2017-01-01

Aluminium-induced oxidative damage caused by excessive ROS production was evaluated in black gram pulse crop. Black gram plants were treated with different aluminium (Al 3+ ) concentrations (10, 50 and 100 μM with pH 4.7) and further the effects of Al 3+ were characterised by means of root growth inhibition, histochemical assay, ROS content analysis, protein carbonylation quantification and 1 H-NMR analysis. The results showed that aluminium induces excessive ROS production which leads to cellular damage, root injury, stunt root growth and other metabolic shifts. In black gram, Al 3+ induces cellular damage at the earliest stage of stress which was characterised from histochemical analysis. From this study, it was observed that prolonged stress can activate certain aluminium detoxification defence mechanism. Probably excessive ROS triggers such defence mechanism in black gram. Al 3+ can induce excessive ROS initially in the root region then transported to other parts of the plant. As much as the Al 3+ concentration increases, the rate of cellular injury and ROS production also increases. But after 72 h of stress, plants showed a lowered ROS level and cellular damage which indicates the upregulation of defensive mechanisms. Metabolic shift analysis also showed that the black gram plant under stress has less metabolic content after 24 h of treatment, but gradually, it was increased after 72 h of treatment. It was assumed that ROS played the most important role as a signalling molecule for aluminium stress in black gram.

Environment exploration and SLAM experiment research based on ROS

Science.gov (United States)

Li, Zhize; Zheng, Wei

2017-11-01

Robots need to get the information of surrounding environment by means of map learning. SLAM or navigation based on mobile robots is developing rapidly. ROS (Robot Operating System) is widely used in the field of robots because of the convenient code reuse and open source. Numerous excellent algorithms of SLAM or navigation are ported to ROS package. hector_slam is one of them that can set up occupancy grid maps on-line fast with low computation resources requiring. Its characters above make the embedded handheld mapping system possible. Similarly, hector_navigation also does well in the navigation field. It can finish path planning and environment exploration by itself using only an environmental sensor. Combining hector_navigation with hector_slam can realize low cost environment exploration, path planning and slam at the same time

Kuula : Sigur Ros rokiklubis. Kammemuusikat Tallinnas. Loomade reekviem

Index Scriptorium Estoniae

2008-01-01

23. aug. esineb Tallinna rokiklubis Rock Café islandi bänd Sigur Ros. Pille Lille muusikute toetusfondi korraldatavast Tallinna Kammermuusika festivalist 17.-23. aug. Tallinna Rootsi Mihkli kirikus, Raekojas ja Jaani kirkus (vt. www.plmf.ee). Kontserdist Nargen Festivali raames 30. ja 31. aug. Tallinna loomaaias

Biomarkers for ALK and ROS1 in Lung Cancer: Immunohistochemistry and Fluorescent In Situ Hybridization.

Science.gov (United States)

Luk, Peter P; Selinger, Christina I; Mahar, Annabelle; Cooper, Wendy A

2018-06-14

- A small proportion of non-small cell lung cancers harbor rearrangements of ALK or ROS1 genes, and these tumors are sensitive to targeted tyrosine kinase inhibitors. It is crucial for pathologists to accurately identify tumors with these genetic alterations to enable patients to access optimal treatments and avoid unnecessary side effects of less effective agents. Although a number of different techniques can be used to identify ALK- and ROS1-rearranged lung cancers, immunohistochemistry and fluorescence in situ hybridization are the mainstays. - To review the role of immunohistochemistry in assessment of ALK and ROS1 rearrangements in lung cancer, focusing on practical issues in comparison with other modalities such as fluorescence in situ hybridization. - This manuscript reviews the current literature on ALK and ROS1 detection using immunohistochemistry and fluorescence in situ hybridization as well as current recommendations. - Although fluorescence in situ hybridization remains the gold standard for detecting ALK and ROS1 rearrangement in non-small cell lung cancer, immunohistochemistry plays an important role and can be an effective screening method for detection of these genetic alterations, or a diagnostic test in the setting of ALK.

ROS dependent copper toxicity in Hydra-biochemical and molecular study.

Science.gov (United States)

Zeeshan, Mohammed; Murugadas, Anbazhagan; Ghaskadbi, Surendra; Rajendran, Ramasamy Babu; Akbarsha, Mohammad Abdulkader

2016-01-01

Copper, an essential microelement, is known to be toxic to aquatic life at concentrations higher than that could be tolerated. Copper-induced oxidative stress has been documented in vitro, yet the in vivo effects of metal-induced oxidative stress have not been extensively studied in the lower invertebrates. The objective of the present study has been to find the effect of ROS-mediated toxicity of environmentally relevant concentrations of copper at organismal and cellular levels in Hydra magnipapillata. Exposure to copper at sublethal concentrations (0.06 and 0.1mg/L) for 24 or 48h resulted in generation of significant levels of intracellular reactive oxygen species (ROS). We infer that the free radicals here originate predominantly at the lysosomes but partly at the mitochondria also as visualized by H2-DHCFDA staining. Quantitative real-time PCR of RNA extracted from copper-exposed polyps revealed dose-dependent up-regulation of all antioxidant response genes (CAT, SOD, GPx, GST, GR, G6PD). Concurrent increase of Hsp70 and FoxO genes suggests the ability of polyps to respond to stress, which at 48h was not the same as at 24h. Interestingly, the transcript levels of all genes were down-regulated at 48h as compared to 24h incubation period. Comet assay indicated copper as a powerful genotoxicant, and the DNA damage was dose- as well as duration-dependent. Western blotting of proteins (Bax, Bcl-2 and caspase-3) confirmed ROS-mediated mitochondrial cell death in copper-exposed animals. These changes correlated well with changes in morphology, regeneration and aspects of reproduction. Taken together, the results indicate increased production of intracellular ROS in Hydra on copper exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

Philip Glass, Scott Walker ja Sigur Ros! / Immo Mihkelson

Index Scriptorium Estoniae

Mihkelson, Immo, 1959-

2007-01-01

Pimedate Ööde 11. filmifestivali muusikafilme - Austraalia "Glass: Philipi portree 12 osas" (rež. Scott Hicks), Islandi "Sigur Ros kodus" (rež. Dean DeBois), Suurbritannia "Scott Walker: 30 Century Man" (rež. Stephen Kijak)

Association between ROS production, swelling and the respirasome integrity in cardiac mitochondria.

Science.gov (United States)

Jang, Sehwan; Javadov, Sabzali

2017-09-15

Although mitochondrial Ca 2+ overload and ROS production play a critical role in mitochondria-mediated cell death, a cause-effect relationship between them remains elusive. This study elucidated the crosstalk between mitochondrial swelling, ROS production, and electron transfer chain (ETC) supercomplexes in rat heart mitochondria in response to Ca 2+ and tert-butyl hydroperoxide (TBH), a lipid-soluble organic peroxide. Results showed that ROS production induced by TBH was significantly increased in the presence of Ca 2+ in a dose-dependent manner. TBH markedly inhibited the state 3 respiration rate with no effect on the mitochondrial swelling. Ca 2+ exerted a slight effect on mitochondrial respiration that was greatly aggravated by TBH. Analysis of supercomplexes revealed a minor difference in the presence of TBH and/or Ca 2+ . However, incubation of mitochondria in the presence of high Ca 2+ (1 mM) or inhibitors of ETC complexes (rotenone and antimycin A) induced disintegration of the main supercomplex, respirasome. Thus, PTP-dependent swelling of mitochondria solely depends on Ca 2+ but not ROS. TBH has no effect on the respirasome while Ca 2+ induces disintegration of the supercomplex only at a high concentration. Intactness of individual ETC complexes I and III is important for maintenance of the structural integrity of the respirasome. Copyright © 2017 Elsevier Inc. All rights reserved.

Desarrollo de un robot móvil compacto integrado en el middleware ROS

Directory of Open Access Journals (Sweden)

André Araújo

2014-07-01

Full Text Available Resumen: En este trabajo se presenta el robot TraxBot y su integración completa en el Robot Operating System (ROS. El TraxBot es una plataforma de robótica móvil, desarrollada y ensamblada en el Instituto de Sistemas y Robótica (ISR Coimbra. El objetivo de este trabajo es reducir drásticamente el tiempo de desarrollo, proporcionando abstracción de hardware y modos de operación intuitiva, permitiendo a los investigadores centrarse en sus motivaciones principales de investigación, por ejemplo, la búsqueda y rescate con múltiples robots o robótica de enjambres. Se describen las potencialidades del TraxBot, que combinado con un controlador de ROS específicamente desarrollado, facilita el uso de varias herramientas para el análisis de datos y la interacción entre múltiples robots, sensores y dispositivos de teleoperación. Para validar el sistema, se llevaron a cabo diversas pruebas experimentales utilizando robots reales y virtuales. Abstract: This paper presents the TraxBot robot and its full integration in the Robotic Operating System (ROS. The TraxBot is a compact mobile robotic platform developed and assembled at the Institute of Systems and Robots (ISR Coimbra. The goal in this work is to drastically decrease the development time, providing hardware abstraction and intuitive operation modes, allowing researchers to focus in their main research motivations, e.g., search and rescue, multi-robot surveillance or swarm robotics. The potentialities of the TraxBot are described which, combined with the ROS driver developed, provide several tools for data analysis and easiness of interaction between multiple robots, sensors and tele-operation devices. To validate the approach, diverse experimental tests using real and virtual simulated robots were conducted. Palabras clave: ROS, robot móvil, sistemas embebidos, diseño, middleware, montaje y test., Keywords: ROS, mobile robot, Arduino, embedded system, design, assembling and testing.

Pectins, ROS homeostasis and UV-B responses in plant roots.

Science.gov (United States)

Yokawa, Ken; Baluška, František

2015-04-01

Light from the sun contains far-red, visible and ultra violet (UV) wavelength regions. Almost all plant species have been evolved under the light environment. Interestingly, several photoreceptors, expressing both in shoots and roots, process the light information during the plant life cycle. Surprisingly, Arabidopsis root apices express besides the UVR8 UV-B receptor, also root-specific UV-B sensing proteins RUS1 and RUS2 linked to the polar cell-cell transport of auxin. In this mini-review, we focus on reactive oxygen species (ROS) signaling and possible roles of pectins internalized via endocytic vesicle recycling system in the root-specific UV-B perception and ROS homeostasis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Establishing the subcellular localization of photodynamically-induced ROS using 3,3′-diaminobenzidine: A methodological proposal, with a proof-of-concept demonstration

DEFF Research Database (Denmark)

Stockert, Juan Carlos; Blazquez-Castro, Alfonso

2016-01-01

The critical involvement of reactive oxygen species (ROS) in both physiological and pathological processes in cell biology makes their detection and assessment a fundamental topic in biomedical research. Established methodologies to study ROS in cell biology take advantage of oxidation reactions...... is proved in a photodynamic model of ROS generation, the principle is applicable to many different scenarios of intracellular ROS production. As a consequence this proposed methodology should greatly complement other techniques aiming at establishing a precise subcellular localization of ROS generation....... between the ROS and a reduced probe. After reacting the probe reveals the presence of ROS either by the appearance of colour (chromogenic reaction) or fluorescence (fluorogenic reaction). However current methodologies rarely allow for a site-specific detection of ROS production. Here we propose...

Qualitative and Quantitative Analysis of ROS-Mediated Oridonin-Induced Oesophageal Cancer KYSE-150 Cell Apoptosis by Atomic Force Microscopy.

Directory of Open Access Journals (Sweden)

Jiang Pi

Full Text Available High levels of intracellular reactive oxygen species (ROS in cells is recognized as one of the major causes of cancer cell apoptosis and has been developed into a promising therapeutic strategy for cancer therapy. However, whether apoptosis associated biophysical properties of cancer cells are related to intracellular ROS functions is still unclear. Here, for the first time, we determined the changes of biophysical properties associated with the ROS-mediated oesophageal cancer KYSE-150 cell apoptosis using high resolution atomic force microscopy (AFM. Oridonin was proved to induce ROS-mediated KYSE-150 cell apoptosis in a dose dependent manner, which could be reversed by N-acetylcysteine (NAC pretreatment. Based on AFM imaging, the morphological damage and ultrastructural changes of KYSE-150 cells were found to be closely associated with ROS-mediated oridonin-induced KYSE-150 cell apoptosis. The changes of cell stiffness determined by AFM force measurement also demonstrated ROS-dependent changes in oridonin induced KYSE-150 cell apoptosis. Our findings not only provided new insights into the anticancer effects of oridonin, but also highlighted the use of AFM as a qualitative and quantitative nanotool to detect ROS-mediated cancer cell apoptosis based on cell biophysical properties, providing novel information of the roles of ROS in cancer cell apoptosis at nanoscale.

Regional meeting of south Oncologist.Third day of Oncologic nursing

International Nuclear Information System (INIS)

2010-12-01

The organization of the Uruguayan Congress represents the greatest effort Oncology Society Medical and Pediatric Uruguay (Sompu) to contribute to the prevention, diagnosis and treatment of cancer in Uruguay. It has developed a program that includes a wide range of topics presenting the latest developments and their significance in clinical practice, through lectures, round tables, and panels-course forum. Selected scientific papers were also discussed sessions for oral and poster presentation way. To ensure a high scientific and educational level to a select group of domestic and foreign experts were invited. The 8th Congress incorporates a panel-led forum for residents and young oncologists Prevention Cancer. Furthermore Course was held on hereditary predispositions to cancer under the Continuing Medical Education Program developed by the Sompu and accredited by the Graduate School. A special meeting in the context of the Latin American Federation of Cancer Societies (FLASCA) Therapeutic Research on Cancer in .In Region Parallel Days also included third Oncology Nursing also developed

The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore.

Science.gov (United States)

Rottenberg, Hagai; Hoek, Jan B

2017-10-01

Excessive production of mitochondrial reactive oxygen species (mROS) is strongly associated with mitochondrial and cellular oxidative damage, aging, and degenerative diseases. However, mROS also induces pathways of protection of mitochondria that slow aging, inhibit cell death, and increase lifespan. Recent studies show that the activation of the mitochondrial permeability transition pore (mPTP), which is triggered by mROS and mitochondrial calcium overloading, is enhanced in aged animals and humans and in aging-related degenerative diseases. mPTP opening initiates further production and release of mROS that damage both mitochondrial and nuclear DNA, proteins, and phospholipids, and also releases matrix NAD that is hydrolyzed in the intermembrane space, thus contributing to the depletion of cellular NAD that accelerates aging. Oxidative damage to calcium transporters leads to calcium overload and more frequent opening of mPTP. Because aging enhances the opening of the mPTP and mPTP opening accelerates aging, we suggest that mPTP opening drives the progression of aging. Activation of the mPTP is regulated, directly and indirectly, not only by the mitochondrial protection pathways that are induced by mROS, but also by pro-apoptotic signals that are induced by DNA damage. We suggest that the integration of these contrasting signals by the mPTP largely determines the rate of cell aging and the initiation of cell death, and thus animal lifespan. The suggestion that the control of mPTP activation is critical for the progression of aging can explain the conflicting and confusing evidence regarding the beneficial and deleterious effects of mROS on health and lifespan. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Shift in aggregation, ROS generation, antioxidative defense, lysozyme and acetylcholinesterase activities in the cells of an Indian freshwater sponge exposed to washing soda (sodium carbonate).

Science.gov (United States)

Mukherjee, Soumalya; Ray, Mitali; Ray, Sajal

2016-09-01

Washing soda, chemically identified as anhydrous sodium carbonate, is a popular cleaning agent among the rural and urban populations of India which often contaminates the freshwater ponds and lakes, the natural habitat of sponge Eunapius carteri. Present investigation deals with estimation of cellular aggregation, generation of ROS and activities of antioxidant enzymes, lysozyme and acetylcholinesterase in the cells of E. carteri under the environmentally realistic concentrations of washing soda. Prolonged treatment of washing soda inhibited the degree of cellular aggregation. Experimental exposure of 8 and 16mg/l of sodium carbonate for 48h elevated the physiological level of reactive oxygen species (ROS) generation in the agranulocytes, semigranulocytes and granulocytes of E. carteri, whereas, treatment of 192h inhibited the ROS generation in three cellular morphotypes. Activities of superoxide dismutase, catalase and glutathione-S-transferase were recorded to be inhibited under prolonged exposure of washing soda. Washing soda mediated inhibition of ROS generation and depletion in the activities of antioxidant enzymes were indicative to an undesirable shift in cytotoxic status and antioxidative defense in E. carteri. Inhibition in the activity of lysozyme under the treatment of sodium carbonate was suggestive to a severe impairment of the innate immunological efficiency of E. carteri distributed in the washing soda contaminated habitat. Washing soda mediated inhibition in the activity of acetylcholinesterase indicated its neurotoxicity in E. carteri. Washing soda, a reported environmental contaminant, affected adversely the immunophysiological status of E. carteri with reference to cellular aggregation, oxidative stress, antioxidative defense, lysozyme and acetylcholinesterase activity. Copyright © 2016 Elsevier Inc. All rights reserved.

ROS-activated calcium signaling mechanisms regulating endothelial barrier function.

Science.gov (United States)

Di, Anke; Mehta, Dolly; Malik, Asrar B

2016-09-01

Increased vascular permeability is a common pathogenic feature in many inflammatory diseases. For example in acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS), lung microvessel endothelia lose their junctional integrity resulting in leakiness of the endothelial barrier and accumulation of protein rich edema. Increased reactive oxygen species (ROS) generated by neutrophils (PMNs) and other inflammatory cells play an important role in increasing endothelial permeability. In essence, multiple inflammatory syndromes are caused by dysfunction and compromise of the barrier properties of the endothelium as a consequence of unregulated acute inflammatory response. This review focuses on the role of ROS signaling in controlling endothelial permeability with particular focus on ALI. We summarize below recent progress in defining signaling events leading to increased endothelial permeability and ALI. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Roles of ROS and Caspases in TRAIL-Induced Apoptosis and Necroptosis in Human Pancreatic Cancer Cells.

Directory of Open Access Journals (Sweden)

Min Zhang

Full Text Available Death signaling provided by tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL can induce death in cancer cells with little cytotoxicity to normal cells; this cell death has been thought to involve caspase-dependent apoptosis. Reactive oxygen species (ROS are also mediators that induce cell death, but their roles in TRAIL-induced apoptosis have not been elucidated fully. In the current study, we investigated ROS and caspases in human pancreatic cancer cells undergoing two different types of TRAIL-induced cell death, apoptosis and necroptosis. TRAIL treatment increased ROS in two TRAIL-sensitive pancreatic cancer cell lines, MiaPaCa-2 and BxPC-3, but ROS were involved in TRAIL-induced apoptosis only in MiaPaCa-2 cells. Unexpectedly, inhibition of ROS by either N-acetyl-L-cysteine (NAC, a peroxide inhibitor, or Tempol, a superoxide inhibitor, increased the annexin V-/propidium iodide (PI+ early necrotic population in TRAIL-treated cells. Additionally, both necrostatin-1, an inhibitor of receptor-interacting protein kinase 1 (RIP1, and siRNA-mediated knockdown of RIP3 decreased the annexin V-/PI+ early necrotic population after TRAIL treatment. Furthermore, an increase in early apoptosis was induced in TRAIL-treated cancer cells under inhibition of either caspase-2 or -9. Caspase-2 worked upstream of caspase-9, and no crosstalk was observed between ROS and caspase-2/-9 in TRAIL-treated cells. Together, these results indicate that ROS contribute to TRAIL-induced apoptosis in MiaPaCa-2 cells, and that ROS play an inhibitory role in TRAIL-induced necroptosis of MiaPaCa-2 and BxPC-3 cells, with caspase-2 and -9 playing regulatory roles in this process.

Nox2-dependent ROS signaling protects against skeletal ageing

Science.gov (United States)

Bone remodeling is age-dependently regulated and changes dramatically during the course of development. Progressive accumulation of reactive oxygen species (ROS), including superoxide, hydrogen peroxide, and hydroxyl radicals, has been suspected to be the leading cause of many inflammatory and degen...

Mitochondrial reactive oxygen species: which ROS signals cardioprotection?

Czech Academy of Sciences Publication Activity Database

Garlid, A. O.; Jabůrek, Martin; Jacobs, J. P.; Garlid, K. D.

2013-01-01

Roč. 305, č. 7 (2013), H960-H968 ISSN 0363-6135 R&D Projects: GA MŠk(CZ) ME09018; GA ČR(CZ) GAP301/11/0662 Institutional support: RVO:67985823 Keywords : KATP channels * ROS signaling * cardiac ischemia * cardioportection * mitochondria Subject RIV: ED - Physiology Impact factor: 4.012, year: 2013

Sensitivity of the green algae Chlamydomonas reinhardtii to gamma radiation: Photosynthetic performance and ROS formation

Energy Technology Data Exchange (ETDEWEB)

Gomes, Tânia, E-mail: tania.gomes@niva.no [Norwegian Institute for Water Research (NIVA), Section of Ecotoxicology and Risk Assessment, Gaustadalléen 21, N-0349, Oslo (Norway); Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432 Ås (Norway); Xie, Li [Norwegian Institute for Water Research (NIVA), Section of Ecotoxicology and Risk Assessment, Gaustadalléen 21, N-0349, Oslo (Norway); Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432 Ås (Norway); Brede, Dag; Lind, Ole-Christian [Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432 Ås (Norway); Department for Environmental Sciences, Faculty of Environmental Science & Technology, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432, Ås (Norway); Solhaug, Knut Asbjørn [Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432 Ås (Norway); Department of Ecology and Natural Resource Management, Norwegian University of Life Sciences (NMBU), Postbox 5003, N-1432, Ås (Norway); Salbu, Brit [Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432 Ås (Norway); Department for Environmental Sciences, Faculty of Environmental Science & Technology, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432, Ås (Norway); and others

2017-02-15

Highlights: • Chlorophyll fluorescence parameters affected at higher dose rates. • Changes in PSII associated with electron transport and energy dissipation pathways. • Dose-dependent ROS production in algae exposed to gamma radiation. • Decrease in photosynthetic efficiency connected to ROS formation. - Abstract: The aquatic environment is continuously exposed to ionizing radiation from both natural and anthropogenic sources, making the characterization of ecological and health risks associated with radiation of large importance. Microalgae represent the main source of biomass production in the aquatic ecosystem, thus becoming a highly relevant biological model to assess the impacts of gamma radiation. However, little information is available on the effects of gamma radiation on microalgal species, making environmental radioprotection of this group of species challenging. In this context, the present study aimed to improve the understanding of the effects and toxic mechanisms of gamma radiation in the unicellular green algae Chlamydomonas reinhardtii focusing on the activity of the photosynthetic apparatus and ROS formation. Algal cells were exposed to gamma radiation (0.49–1677 mGy/h) for 6 h and chlorophyll fluorescence parameters obtained by PAM fluorometry, while two fluorescent probes carboxy-H{sub 2}DFFDA and DHR 123 were used for the quantification of ROS. The alterations seen in functional parameters of C. reinhardtii PSII after 6 h of exposure to gamma radiation showed modifications of PSII energy transfer associated with electron transport and energy dissipation pathways, especially at the higher dose rates used. Results also showed that gamma radiation induced ROS in a dose-dependent manner under both light and dark conditions. The observed decrease in photosynthetic efficiency seems to be connected to the formation of ROS and can potentially lead to oxidative stress and cellular damage in chloroplasts. To our knowledge, this is the first

Sensitivity of the green algae Chlamydomonas reinhardtii to gamma radiation: Photosynthetic performance and ROS formation

International Nuclear Information System (INIS)

Gomes, Tânia; Xie, Li; Brede, Dag; Lind, Ole-Christian; Solhaug, Knut Asbjørn; Salbu, Brit

2017-01-01

Highlights: • Chlorophyll fluorescence parameters affected at higher dose rates. • Changes in PSII associated with electron transport and energy dissipation pathways. • Dose-dependent ROS production in algae exposed to gamma radiation. • Decrease in photosynthetic efficiency connected to ROS formation. - Abstract: The aquatic environment is continuously exposed to ionizing radiation from both natural and anthropogenic sources, making the characterization of ecological and health risks associated with radiation of large importance. Microalgae represent the main source of biomass production in the aquatic ecosystem, thus becoming a highly relevant biological model to assess the impacts of gamma radiation. However, little information is available on the effects of gamma radiation on microalgal species, making environmental radioprotection of this group of species challenging. In this context, the present study aimed to improve the understanding of the effects and toxic mechanisms of gamma radiation in the unicellular green algae Chlamydomonas reinhardtii focusing on the activity of the photosynthetic apparatus and ROS formation. Algal cells were exposed to gamma radiation (0.49–1677 mGy/h) for 6 h and chlorophyll fluorescence parameters obtained by PAM fluorometry, while two fluorescent probes carboxy-H 2 DFFDA and DHR 123 were used for the quantification of ROS. The alterations seen in functional parameters of C. reinhardtii PSII after 6 h of exposure to gamma radiation showed modifications of PSII energy transfer associated with electron transport and energy dissipation pathways, especially at the higher dose rates used. Results also showed that gamma radiation induced ROS in a dose-dependent manner under both light and dark conditions. The observed decrease in photosynthetic efficiency seems to be connected to the formation of ROS and can potentially lead to oxidative stress and cellular damage in chloroplasts. To our knowledge, this is the first report

Advanced Query and Data Mining Capabilities for MaROS

Science.gov (United States)

Wang, Paul; Wallick, Michael N.; Allard, Daniel A.; Gladden, Roy E.; Hy, Franklin H.

2013-01-01

The Mars Relay Operational Service (MaROS) comprises a number of tools to coordinate, plan, and visualize various aspects of the Mars Relay network. These levels include a Web-based user interface, a back-end "ReSTlet" built in Java, and databases that store the data as it is received from the network. As part of MaROS, the innovators have developed and implemented a feature set that operates on several levels of the software architecture. This new feature is an advanced querying capability through either the Web-based user interface, or through a back-end REST interface to access all of the data gathered from the network. This software is not meant to replace the REST interface, but to augment and expand the range of available data. The current REST interface provides specific data that is used by the MaROS Web application to display and visualize the information; however, the returned information from the REST interface has typically been pre-processed to return only a subset of the entire information within the repository, particularly only the information that is of interest to the GUI (graphical user interface). The new, advanced query and data mining capabilities allow users to retrieve the raw data and/or to perform their own data processing. The query language used to access the repository is a restricted subset of the structured query language (SQL) that can be built safely from the Web user interface, or entered as freeform SQL by a user. The results are returned in a CSV (Comma Separated Values) format for easy exporting to third party tools and applications that can be used for data mining or user-defined visualization and interpretation. This is the first time that a service is capable of providing access to all cross-project relay data from a single Web resource. Because MaROS contains the data for a variety of missions from the Mars network, which span both NASA and ESA, the software also establishes an access control list (ACL) on each data record

The alternative Medicago truncatula defense proteome of ROS – defective transgenic roots during early microbial infection

Directory of Open Access Journals (Sweden)

Leonard Muriithi Kiirika

2014-07-01

Full Text Available ROP-type GTPases of plants function as molecular switches within elementary signal transduction pathways such as the regulation of ROS synthesis via activation of NADPH oxidases (RBOH-respiratory burst oxidase homologue in plants. Previously, we reported that silencing of the Medicago truncatula GTPase MtROP9 led to reduced ROS production and suppressed induction of ROS-related enzymes in transgenic roots (MtROP9i infected with pathogenic (Aphanomyces euteiches and symbiotic microorganisms (Glomus intraradices, Sinorhizobium meliloti. While fungal infections were enhanced, S. meliloti infection was drastically impaired. In this study, we investigate the temporal proteome response of M. truncatula MtROP9i transgenic roots during the same microbial interactions under conditions of deprived potential to synthesize ROS. In comparison with control roots (Mtvector, we present a comprehensive proteomic analysis using sensitive MS protein identification. For four early infection time-points (1, 3, 5, 24 hpi, 733 spots were found to be different in abundance: 213 spots comprising 984 proteins (607 unique were identified after S. meliloti infection, 230 spots comprising 796 proteins (580 unique after G. intraradices infection, and 290 spots comprising 1240 proteins (828 unique after A. euteiches infection. Data evaluation by GelMap in combination with a heatmap tool allowed recognition of key proteome changes during microbial interactions under conditions of hampered ROS synthesis. Overall, the number of induced proteins in MtROP9i was low as compared with controls, indicating a dual function of ROS in defense signaling as well as alternative response patterns activated during microbial infection. Qualitative analysis of induced proteins showed that enzymes linked to ROS production and scavenging were highly induced in control roots, while in MtROP9i the majority of proteins were involved in alternative defense pathways such as cell wall and protein

MaROS Strategic Relay Planning and Coordination Interfaces

Science.gov (United States)

Allard, Daniel A.

2010-01-01

The Mars Relay Operations Service (MaROS) is designed to provide planning and analysis tools in support of ongoing Mars Network relay operations. Strategic relay planning requires coordination between lander and orbiter mission ground data system (GDS) teams to schedule and execute relay communications passes. MaROS centralizes this process, correlating all data relevant to relay coordination to provide a cohesive picture of the relay state. Service users interact with the system through thin-layer command line and web user interface client applications. Users provide and utilize data such as lander view periods of orbiters, Deep Space Network (DSN) antenna tracks, and reports of relay pass performance. Users upload and download relevant relay data via formally defined and documented file structures including some described in Extensible Markup Language (XML). Clients interface with the system via an http-based Representational State Transfer (ReST) pattern using Javascript Object Notation (JSON) formats. This paper will provide a general overview of the service architecture and detail the software interfaces and considerations for interface design.

Integración del brazo robot IRB120 en entorno ROS-MATLAB

OpenAIRE

Gómez Cuadrado, José Manuel

2017-01-01

Este proyecto usa el entorno ROS (Robot Operating System) para desarrollar el control del brazo robot IRB 120 y su implementación en el entorno de trabajo MATLAB. Se explicará la creación del modelo del robot, la planificación de trayectorias y la comunicación con dicho robot. This project uses the ROS (Robot Operating System) environment for developing the control of the IRB 120 robotic arm and its implementation in the MATLAB working environment. It will explain the creation of the...

REGINALDO, Lucilene. Os Rosários dos Angolas: Irmandades de africanos e crioulos na Bahia setecentista.

Directory of Open Access Journals (Sweden)

Ênio José da Costa Brito

2013-06-01

Full Text Available Os Rosários dos Angolas realiza um estudo da Irmandade de Nossa Senhora do Rosário dos Pretos das Portas do Carmo( Bahia A novidade do estudo está nos subsidios coletados na Africa, Portugal e Brasil , no resgate da presença banto na Bahia e na abertura para um dialogo das cosmovisões banto e cristã.REGINALDO, Lucilene. Os Rosários dos Angolas: Irmandades de africanos e crioulos na Bahia setecentista. São Paulo: Alameda, 2011. 416p. ISBN 978-85-7939-082-1 

Deliberate ROS production and auxin synergistically trigger the asymmetrical division generating the subsidiary cells in Zea mays stomatal complexes.

Science.gov (United States)

Livanos, Pantelis; Galatis, Basil; Apostolakos, Panagiotis

2016-07-01

Subsidiary cell generation in Poaceae is an outstanding example of local intercellular stimulation. An inductive stimulus emanates from the guard cell mother cells (GMCs) towards their laterally adjacent subsidiary cell mother cells (SMCs) and triggers the asymmetrical division of the latter. Indole-3-acetic acid (IAA) immunolocalization in Zea mays protoderm confirmed that the GMCs function as local sources of auxin and revealed that auxin is polarly accumulated between GMCs and SMCs in a timely-dependent manner. Besides, staining techniques showed that reactive oxygen species (ROS) exhibit a closely similar, also time-dependent, pattern of appearance suggesting ROS implication in subsidiary cell formation. This phenomenon was further investigated by using the specific NADPH-oxidase inhibitor diphenylene iodonium, the ROS scavenger N-acetyl-cysteine, menadione which leads to ROS overproduction, and H2O2. Treatments with diphenylene iodonium, N-acetyl-cysteine, and menadione specifically blocked SMC polarization and asymmetrical division. In contrast, H2O2 promoted the establishment of SMC polarity and subsequently subsidiary cell formation in "younger" protodermal areas. Surprisingly, H2O2 favored the asymmetrical division of the intervening cells of the stomatal rows leading to the creation of extra apical subsidiary cells. Moreover, H2O2 altered IAA localization, whereas synthetic auxin analogue 1-napthaleneacetic acid enhanced ROS accumulation. Combined treatments with ROS modulators along with 1-napthaleneacetic acid or 2,3,5-triiodobenzoic acid, an auxin efflux inhibitor, confirmed the crosstalk between ROS and auxin functioning during subsidiary cell generation. Collectively, our results demonstrate that ROS are critical partners of auxin during development of Z. mays stomatal complexes. The interplay between auxin and ROS seems to be spatially and temporarily regulated.

Platinum nanozymes recover cellular ROS homeostasis in an oxidative stress-mediated disease model

Science.gov (United States)

Moglianetti, Mauro; de Luca, Elisa; Pedone, Deborah; Marotta, Roberto; Catelani, Tiziano; Sartori, Barbara; Amenitsch, Heinz; Retta, Saverio Francesco; Pompa, Pier Paolo

2016-02-01

In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide dismutase, catalase, and peroxidase enzymes, with similar or even superior performance than natural enzymes, along with higher adaptability to the changes in environmental conditions. We then exploited their potent activity as radical scavenging materials in a cellular model of an oxidative stress-related disorder, namely human Cerebral Cavernous Malformation (CCM) disease, which is associated with a significant increase in intracellular ROS levels. Noteworthily, we found that Pt nanozymes can efficiently reduce ROS levels, completely restoring the cellular physiological homeostasis.In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide

Rod and cone photoreceptor cells produce ROS in response to stress in a live retinal explant system.

LENUS (Irish Health Repository)

Bhatt, Lavinia

2010-01-01

PURPOSE: The production of reactive oxygen species (ROS) can lead to oxidative stress, which is a strong contributory factor to many ocular diseases. In this study, the removal of trophic factors is used as a model system to investigate the effects of stress in the retina. The aims were to determine if both rod and cone photoreceptor cells produce ROS when they are deprived of trophic factor support and to demonstrate if the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzymes are responsible for this ROS production. METHODS: Retinas were explanted from mice aged between postnatal days 8-10 and cultured overnight. The following morning, confocal microscopy combined with various fluorescent probes was used to detect the production of ROS. Each time peanut agglutinin (PNA), a cone photoreceptor marker, was used to facilitate orientation of the retina. Dihydroethidium and dihydrorhodamine 123 (DHR123) were used to determine which cells produce ROS. Subsequently, western blots of retinal serial sections were used to detect the presence of Noxs in the different retinal layers. The Nox inhibitor apocynin was then tested to determine if it altered the production of ROS within these cells. RESULTS: Live retinal explants, viewed at high magnifications using confocal microscopy, displayed an increase in the fluorescent products of dihydroethidium and DHR123 upon serum removal when compared to controls. DHR123 fluorescence, once oxidized, localized to mitochondria and was found in the same focal plane as the PNA staining. This showed that cones and rods produced ROS when stressed. Retinal serial sectioning established that the photoreceptor layer expressed Nox4, dual oxidase (Duox) 1, and Duox2 at varying levels. Finally, the Nox inhibitor apocynin decreased the burst stimulated by the stress of serum removal. CONCLUSIONS: Confocal microscopy and PNA staining allowed differentiation of cell types within the outermost layers of the retina, demonstrating

Gynecologic oncologists' attitudes and practices relating to integrative medicine: results of a nationwide AGO survey.

Science.gov (United States)

Klein, Evelyn; Beckmann, Matthias W; Bader, Werner; Brucker, Cosima; Dobos, Gustav; Fischer, Dorothea; Hanf, Volker; Hasenburg, Annette; Jud, Sebastian M; Kalder, Matthias; Kiechle, Marion; Kümmel, Sherko; Müller, Andreas; Müller, Myrjam-Alice T; Paepke, Daniela; Rotmann, Andre-Robert; Schütz, Florian; Scharl, Anton; Voiss, Petra; Wallwiener, Markus; Witt, Claudia; Hack, Carolin C

2017-08-01

The growing popularity and acceptance of integrative medicine is evident both among patients and among the oncologists treating them. As little data are available regarding health-care professionals' knowledge, attitudes, and practices relating to the topic, a nationwide online survey was designed. Over a period of 11 weeks (from July 15 to September 30, 2014) a self-administered, 17-item online survey was sent to all 676 members of the Research Group on Gynecological Oncology (Arbeitsgemeinschaft Gynäkologische Onkologie) in the German Cancer Society. The questionnaire items addressed the use of integrative therapy methods, fields of indications for them, advice services provided, level of specific qualifications, and other topics. Of the 104 respondents (15.4%) using integrative medicine, 93% reported that integrative therapy was offered to breast cancer patients. The second most frequent type of tumor in connection with which integrative therapy methods were recommended was ovarian cancer, at 80% of the participants using integrative medicine. Exercise, nutritional therapy, dietary supplements, herbal medicines, and acupuncture were the methods the patients were most commonly advised to use. There is considerable interest in integrative medicine among gynecological oncologists, but integrative therapy approaches are at present poorly implemented in routine clinical work. Furthermore there is a lack of specific training. Whether future efforts should focus on extending counseling services on integrative medicine approaches in gynecologic oncology or not, have to be discussed. Evidence-based training on integrative medicine should be implemented in order to safely guide patients in their wish to do something by themselves.

Methylcholanthrene-Induced Sarcomas Develop Independently from NOX2-Derived ROS.

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Maarten A Ligtenberg

Full Text Available Reactive oxygen species (ROS produced by the inducible NADPH oxidase type 2 (NOX2 complex are essential for clearing certain infectious organisms but may also have a role in regulating inflammation and immune response. For example, ROS is involved in myeloid derived suppressor cell (MDSC- and regulatory T cell (T(reg mediated T- and NK-cell suppression. However, abundant ROS produced within the tumor microenvironment, or by the tumor itself may also yield oxidative stress, which can blunt anti-tumor immune responses as well as eventually leading to tumor toxicity. In this study we aimed to decipher the role of NOX2-derived ROS in a chemically (by methylcholanthrene (MCA induced sarcoma model. Superoxide production by NOX2 requires the p47(phox (NCF1 subunit to organize the formation of the NOX2 complex on the cell membrane. Homozygous mutant mice (NCF1*/* have a functional loss of their super oxide burst while heterozygous mice (NCF1*/+ retain this key function. Mice harboring either a homo- or a heterozygous mutation were injected intramuscularly with MCA to induce sarcoma formation. We found that NOX2 functionality does not determine tumor incidence in the tested MCA model. Comprehensive immune monitoring in tumor bearing mice showed that infiltrating immune cells experienced an increase in their oxidative state regardless of the NOX2 functionality. While MCA-induced sarcomas where characterized by a T(reg and MDSC accumulation, no significant differences could be found between NCF1*/* and NCF1*/+ mice. Furthermore, infiltrating T cells showed an increase in effector-memory cell phenotype markers in both NCF1*/* and NCF1*/+ mice. Tumors established from both NCF1*/* and NCF1*/+ mice were tested for their in vitro proliferative capacity as well as their resistance to cisplatin and radiation therapy, with no differences being recorded. Overall our findings indicate that NOX2 activity does not play a key role in tumor development or immune cell

Implementation of a mobile base with evasion of obstacles using ROS navigation

International Nuclear Information System (INIS)

Arauz Villegas, Carolina

2013-01-01

A mobile base is implemented with evasion of obstacles using ROS Navigation. The simulation of that mobile base is performed with the 2D Stage simulator, firstly; and once understanded the operation of Navigation has proceeded to build the mobile base. The mobile base has had two DC motors, an Asus Xtion sensor, a netbook and a stm32f4-discovery microcontroller. ROS in the netbook was installed and then serial communication over USB was achieved between the netbook and the microcontroller. The microcontroller has received the velocity data sent by move_base of navigation through that communication and sends the odometry data back. A PWM control is implemented for the driving and for the speed of the motors having a control PI for the cycle of work of the same. The encoder interface of the microcontroller was used for the data acquisition of odometry. The communication between ROS and the mobile base was integrated to the navigation, which has allowed to generate mapping, location and move safely from a starting point to a point of arrival sending speed messages. (author) [es

Carbon black nanoparticles promote endothelial activation and lipid accumulation in macrophages independently of intracellular ROS production

DEFF Research Database (Denmark)

Cao, Yi; Roursgaard, Martin; Danielsen, Pernille Høgh

2014-01-01

, the concentrations of CB to induce lipid accumulation were lower than the concentrations to promote intracellular ROS production in THP-1a cells. In conclusion, exposure to nano-sized CB induced endothelial dysfunction and foam cell formation, which was not dependent on intracellular ROS production....... and WST-1 assays, especially in THP-1 and THP-1a cells. The CB exposure decreased the glutathione (GSH) content in THP-1 and THP-1a cells, whereas GSH was increased in HUVECs. The reactive oxygen species (ROS) production was increased in all cell types after CB exposure. A reduction of the intracellular...... GSH concentration by buthionine sulfoximine (BSO) pre-treatment further increased the CB-induced ROS production in THP-1 cells and HUVECs. The expression of adhesion molecules ICAM-1 and VCAM-1, but not adhesion of THP-1 to HUVECs or culture dishes, was elevated by CB exposure, whereas these effects...

Stanniocalcin-1 Protects a Mouse Model from Renal Ischemia-Reperfusion Injury by Affecting ROS-Mediated Multiple Signaling Pathways.

Science.gov (United States)

Liu, Dajun; Shang, Huiping; Liu, Ying

2016-07-12

Stanniocalcin-1 (STC-1) protects against renal ischemia-reperfusion injury (RIRI). However, the molecular mechanisms remain widely unknown. STC-1 inhibits reactive oxygen species (ROS), whereas most ROS-mediated pathways are associated with ischemic injury. Therefore, to explore the mechanism, the effects of STC-1 on ROS-medicated pathways were studied. Non-traumatic vascular clamps were used to establish RIRI mouse models. The serum levels of STC-1, interleukin-6 (IL-6), interferon (IFN) γ, P53, and capase-3 were measured by ELISA kits. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by fluorescence spectrofluorometer. All these molecules changed significantly in a RIRI model mouse when compared with those in a sham control. Kidney cells were isolated from sham and model mice. STC-1 was overexpressed or knockout in these kidney cells. The molecules in ROS-medicated pathways were measured by real-time quantitative PCR and Western blot. The results showed that STC-1 is an effective ROS scavenger. The serum levels of STC-1, MDA and SOD activity were increased while the serum levels of IL-6, iIFN-γ, P53, and capase-3 were decreased in a model group when compared with a sham control (p ROS-mediated molecules. Therefore, STC-1 maybe improve anti-inflammation, anti-oxidant and anti-apoptosis activities by affecting ROS-mediated pathways, especially the phospho-modifications of the respective proteins, resulting in the increase of SOD and reduce of capase-3, p53, IL-6 and IFN-γ.

Studies on antibacterial activity of ZnO nanoparticles by ROS induced lipid peroxidation.

Science.gov (United States)

Dutta, R K; Nenavathu, Bhavani P; Gangishetty, Mahesh K; Reddy, A V R

2012-06-01

Recent studies indicated the role of ROS toward antibacterial activity. In our study we report ROS mediated membrane lipid oxidation of Escherichia coli treated with ZnO nanoparticles (NPs) as supported by detection and spectrophotometric measurement of malondialdehyde (MDA) by TBARS (thiobarbituric acid-reactive species) assay. The antibacterial effects of ZnO NPs were studied by measuring the growth curve of E. coli, which showed concentration dependent bacteriostatic and bacteriocidal effects of ZnO NPs. The antibacterial effects were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Further, antibacterial effect of ZnO NPs was found to decrease by introducing histidine to the culture medium treated with ZnO NPs. The ROS scavenging action of histidine was confirmed by treating histidine to the batch of Escherichia coli+ZnO NPs at the end of the lag phase of the growth curve (Set-I) and during inoculation (Set-II). A moderate bacteriostatic effect (lag in the E. coli growth) was observed in Set-II batch while Set-I showed no bacteriostatic effect. From these evidences we confirmed that the antibacterial effect of bare as well as TG capped ZnO NPs were due to membrane lipid peroxidation caused by the ROS generated during ZnO NPs interaction in culture medium. Copyright © 2012 Elsevier B.V. All rights reserved.

Critical role of mitochondrial ROS is dependent on their site of production on the electron transport chain in ischemic heart.

Science.gov (United States)

Madungwe, Ngonidzashe B; Zilberstein, Netanel F; Feng, Yansheng; Bopassa, Jean C

2016-01-01

Reactive oxygen species (ROS) generation has been implicated in many pathologies including ischemia/reperfusion (I/R) injury. This led to multiple studies on antioxidant therapies to treat cardiovascular diseases but paradoxically, results have so far been mixed as ROS production can be beneficial as a signaling mechanism and in cardiac protection via preconditioning interventions. We investigated whether the differential impact of increased ROS in injury as well as in protection could be explained by their site of production on the mitochondrial electron transport chain. Using amplex red to measure ROS production, we found that mitochondria isolated from hearts after I/R produced more ROS than non-ischemic when complex I substrate (glutamate/malate) was used. Interestingly, the substrates of complex II (succinate) and ubiquinone (sn-glycerol 3-phosphate, G3P) produced less ROS in mitochondria from I/R hearts compared to normal healthy hearts. The inhibitors of complex I (rotenone) and complex III (antimycin A) increased ROS production when glutamate/malate and G3P were used; in contrast, they reduced ROS production when the complex II substrate was used. Mitochondrial calcium retention capacity required to induce mitochondrial permeability transition pore (mPTP) opening was measured using calcium green fluorescence and was found to be higher when mitochondria were treated with G3P and succinate compared to glutamate/malate. Furthermore, Langendorff hearts treated with glutamate/malate exhibited reduced cardiac functional recovery and increased myocardial infarct size compared to hearts treated with G3P. Thus, ROS production by the stimulated respiratory chain complexes I and III has opposite roles: cardio-deleterious when produced in complex I and cardio-protective when produced in complex III. The mechanism of these ROS involves the inhibition of the mPTP opening, a key event in cell death following ischemia/reperfusion injury.

ROS are critical for endometrial breakdown via NF-κB-COX-2 signaling in a female mouse menstrual-like model.

Science.gov (United States)

Wu, Bin; Chen, Xihua; He, Bin; Liu, Shuyan; Li, Yunfeng; Wang, Qianxing; Gao, Haijun; Wang, Shufang; Liu, Jianbing; Zhang, Shucheng; Xu, Xiangbo; Wang, Jiedong

2014-09-01

Progesterone withdrawal triggers endometrial breakdown and shedding during menstruation. Menstruation results from inflammatory responses; however, the role of reactive oxygen species (ROS) in menstruation remains unclear. In this study, we explored the role of ROS in endometrial breakdown and shedding. We found that ROS levels were significantly increased before endometrial breakdown in a mouse menstrual-like model. Vaginal smear inspection, morphology of uterine horns, and endometrial histology examination showed that a broad range of ROS scavengers significantly inhibited endometrial breakdown in this model. Furthermore, Western blot and immunohistochemical analysis showed that the intracellular translocation of p50 and p65 from the cytoplasm into the nucleus was blocked by ROS scavengers and real-time PCR showed that cyclooxygenase-2 (COX-2) mRNA expression was decreased by ROS scavengers. Similar changes also occurred in human stromal cells in vitro. Furthermore, Western blotting and real-time PCR showed that one ROS, hydrogen peroxide (H2O2), promoted translocation of p50 and p65 from the cytoplasm to the nucleus and increased COX-2 mRNA expression along with progesterone maintenance. The nuclear factor κB inhibitor MG132 reduced the occurrence of these changes in human stromal cells in vitro. Viewed as a whole, our results provide evidence that certain ROS are important for endometrial breakdown and shedding in a mouse menstrual-like model and function at least partially via nuclear factor-κB/COX-2 signaling. Similar changes observed in human stromal cells could also implicate ROS as important mediators of human menstruation.

NADPH Oxidase-Mediated ROS Production Determines Insulin's Action on the Retinal Microvasculature.

Science.gov (United States)

Kida, Teruyo; Oku, Hidehiro; Horie, Taeko; Matsuo, Junko; Kobayashi, Takatoshi; Fukumoto, Masanori; Ikeda, Tsunehiko

2015-10-01

To determine whether insulin induces nitric oxide (NO) formation in retinal microvessels and to examine the effects of high glucose on the formation of NO. Freshly isolated rat retinal microvessels were incubated in normal (5.5 mM) or high (20 mM) glucose with or without insulin (100 nM). The levels of insulin-induced NO and reactive oxygen species (ROS) in the retinal microvessels were determined semiquantitatively using fluorescent probes, 4,5-diaminofluorescein diacetate, and hydroethidine, respectively, and a laser scanning confocal microscope. The insulin-induced changes of NO in rat retinal endothelial cells and pericytes cultured at different glucose concentrations (5.5 and 25 mM) were determined using flow cytometry. Nitric oxide synthase (NOS) protein levels were determined by Western blot analysis; intracellular levels of ROS were determined using fluorescence-activated cell sorting (FACS) analysis of ethidium fluorescence; and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase RNA expression was quantified using real-time PCR. Exposure of microvessels to insulin under normal glucose conditions led to a significant increase in NO levels; however, this increase was significantly suppressed when the microvessels were incubated under high glucose conditions. Intracellular levels of ROS were significantly increased in both retinal microvessels and cultured microvascular cells under high glucose conditions. The expression of NOS and NADPH oxidase were significantly increased in endothelial cells and pericytes under high glucose conditions. The increased formation of NO by insulin and its suppression by high glucose conditions suggests that ROS production mediated by NADPH oxidase is important by insulin's effect on the retinal microvasculature.

Exogenous ROS-induced cell sheet transfer based on hematoporphyrin-polyketone film via a one-step process.

Science.gov (United States)

Koo, Min-Ah; Lee, Mi Hee; Kwon, Byeong-Ju; Seon, Gyeung Mi; Kim, Min Sung; Kim, Dohyun; Nam, Ki Chang; Park, Jong-Chul

2018-04-01

To date, most of invasive cell sheet harvesting methods have used culture surface property variations, such as wettability, pH, electricity, and magnetism, to induce cell detachment. These methods that rely on surface property changes are effective when cell detachment prior to application is necessary, but of limited use when used for cell sheet transfer to target regions. The study reports a new reactive oxygen species (ROS)-induced strategy based on hematoporphyrin-incorporated polyketone film (Hp-PK film) to transfer cell sheets directly to target areas without an intermediate harvesting process. After green LED (510 nm) irradiation, production of exogenous ROS from the Hp-PK films induces cell sheet detachment and transfer. The study suggests that ROS-induced cell detachment property of the Hp-PK film is closely related to conformational changes of extracellular matrix (ECM) proteins. Also, this strategy with the Hp-PK film can be applied by regulating production rate of exogenous ROS in various types of cells, including fibroblasts, mesenchymal stem cells and keratinocytes. In conclusion, ROS-induced method using the Hp-PK film can be used for one-step cell sheet transplantation and has potential in biomedical applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of exposure to high glucose on primary cultured hippocampal neurons: involvement of intracellular ROS accumulation.

Science.gov (United States)

Liu, Di; Zhang, Hong; Gu, Wenjuan; Zhang, Mengren

2014-06-01

Recent studies showed that hyperglycemia is the main trigger of diabetic cognitive impairment and can cause hippocampus abnormalities. The goal of this study is to explore the effects of different concentrations of high glucose for different exposure time on cell viability as well as intracellular reactive oxygen species (ROS) generation of primary cultured hippocampal neurons. Hippocampal neurons were exposed to different concentrations of high glucose (50, 75, 100, 125, and 150 mM) for 24, 48, 72 and 96 h. Cell viability and nuclear morphology were evaluated by MTT and Hoechst assays, respectively. Intracellular ROS were monitored using the fluorescent probe DCFH-DA. The results showed that, compared with control group, the cell viability of all high glucose-treated groups decreased significantly after 72 h and there also was a significant increase of apoptotic nuclei in high glucose-treated groups from 72 to 96 h. Furthermore, 50 mM glucose induced a peak rise in ROS generation at 24 h and the intracellular ROS levels of 50 mM glucose group were significantly higher than the corresponding control group from 6 to 72 h. These results suggest that hippocampal neurons could be injured by high glucose exposure and the neuronal injury induced by high glucose is potentially mediated through intracellular ROS accumulation.

Response to crizotinib in a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant

Science.gov (United States)

Zhao, Zheng; Song, Zhangjun; Wang, Xuwei; Sun, Haifeng; Yang, Xiaomin; Yuan, Yong; Yu, Pan

2017-01-01

ROS1 fusion is a common genetic alteration in non-small-cell lung cancer. Crizotinib, an anaplastic lymphoma kinase inhibitor, shows efficacy in the treatment of lung cancer cases with ROS1 translocation. We report the response to crizotinib of a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant, which was different from the two common SLC34A2-ROS1 fusion types reported in the literature. After crizotinib administration, overall recovery was good in this patient; the primary lesion was successfully treated, the lymph node metastases had disappeared, and the metabolism was normal. PMID:28860822

Ny forskning: Derfor virker ros ikke mod stress

DEFF Research Database (Denmark)

Pedersen, Pernille

2015-01-01

Ny forskning peger på, at stressede medarbejdere overhører din ros og anerkendelse, hvis de føler skam. Skam over ikke at kunne slå til på arbejdet. Vil du hjælpe en stresset medarbejder, skal du forebygge, at de føler sig skamfulde. Læs her anbefalinger til, hvordan du bedst hjælper din stressed...

Iron overload promotes erythroid apoptosis through regulating HIF-1a/ROS signaling pathway in patients with myelodysplastic syndrome.

Science.gov (United States)

Zheng, Qing-Qing; Zhao, You-Shan; Guo, Juan; Zhao, Si-da; Song, Lu-Xi; Fei, Cheng-Ming; Zhang, Zheng; Li, Xiao; Chang, Chun-Kang

2017-07-01

Erythroid apoptosis increases significantly in myelodysplastic syndrome (MDS) patients with iron overload, but the underlying mechanism is not fully clear. In this study, we aim to explore the effect of HIF-1a/ROS on erythroid apoptosis in MDS patients with iron overload. We found that iron overload injured cellular functions through up-regulating ROS levels in MDS/AML cells, including inhibited cell viability, increased cell apoptosis and blocked cell cycle at G0/G1 phase. Interestingly, overexpression of hypoxia inducible factor-1a (HIF-1a), which was under-expressed in iron overload models, reduced ROS levels and attenuated cell damage caused by iron overload in MDS/AML cells. And gene knockdown of HIF-1a got the similar results as iron overload in MDS/AML cells. Furthermore, iron overload caused high erythroid apoptosis was closely related with ROS in MDS patients. Importantly, the HIF-1a protein levels of erythrocytes elevated obviously after incubation with desferrioxamine (DFO) from MDS patients with iron overload, accompanied by ROS levels inhibited and erythroid apoptosis reduced. Taken together, our findings determine that the HIF-1a/ROS signaling pathway plays a key role in promoting erythroid apoptosis in MDS patients with iron overload. Copyright © 2017 Elsevier Ltd. All rights reserved.

Palmitate induces VSMC apoptosis via toll like receptor (TLR)4/ROS/p53 pathway.

Science.gov (United States)

Zhang, Yuanjun; Xia, Guanghao; Zhang, Yaqiong; Liu, Juxiang; Liu, Xiaowei; Li, Weihua; Lv, Yaya; Wei, Suhong; Liu, Jing; Quan, Jinxing

2017-08-01

Toll-like receptor 4 (TLR4) has been implicated in vascular inflammation, as well as in the pathogenesis of atherosclerosis and diabetes. Vascular smooth muscle cell (VSMC) apoptosis has been shown to induce plaque vulnerability in atherosclerosis. Previous studies reported that palmitate induced apoptosis in VSMCs; however, the role of TLR4 in palmitate-induced apoptosis in VSMCs has not yet been defined. In this study, we investigated whether or not palmitate-induced apoptosis depended on the activation of the TLR4 pathway. VSMCs were treated with or without palmitate, CRISPR/Cas9z-mediated genome editing methods were used to deplete TLR4 expression, while NADPH oxidase inhibitors were used to inhibit reactive oxygen species (ROS) generation. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, ROS was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method, the mRNA and protein expression levels of caspase 3, caspase 9, BCL-2 and p53 were studied by real-time polymerase chain reaction (RT-PCR) and ELISA. Palmitate significantly promotes VSMC apoptosis, ROS generation, and expression of caspase 3, caspase 9 and p53; while NADPH oxidase inhibitor pretreatment markedly attenuated these effects. Moreover, knockdown of TLR4 significantly blocked palmitate-induced ROS generation and VSMC apoptosis accompanied by inhibition of caspase 3, caspase 9, p53 expression and restoration of BCL-2 expression. Our results suggest that palmitate-induced apoptosis depends on the activation of the TLR4/ROS/p53 signaling pathway, and that TLR4 may be a potential therapeutic target for the prevention and treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Benzoquinone activates the ERK/MAPK signaling pathway via ROS production in HL-60 cells

International Nuclear Information System (INIS)

Ruiz-Ramos, Ruben; Cebrian, Mariano E.; Garrido, Efrain

2005-01-01

Benzene (BZ) is a class I carcinogen and its oxidation to reactive intermediates is a prerequisite of hematoxicity and myelotoxicity. The generated metabolites include hydroquinone, which is further oxidized to the highly reactive 1,4-benzoquinone (BQ) in bone marrow. Therefore, we explored the mechanisms underlying BQ-induced HL-60 cell proliferation by studying the role of BQ-induced reactive oxygen species (ROS) in the activation of the ERK-MAPK signaling pathway. BQ treatment (0.01-30 μM) showed that doses below 10 μM did not significantly reduce viability. ROS production after 3 μM BQ treatment increased threefold; however, catalase addition reduced ROS generation to basal levels. FACS analysis showed that BQ induced a fivefold increase in the proportion of cells in S-phase. We also observed a high proportion of Bromodeoxyuridine (BrdU) stained cells, indicating a higher DNA synthesis rate. BQ also produced rapid and prolonged phosphorylation of ERK1/2 proteins. Simultaneous treatment with catalase or PD98059, a potent MEK protein inhibitor, reduced cell recruitment into the S-phase and also abolished the ERK1/2 protein phosphorylation induced by BQ, suggesting that MEK/ERK is an important pathway involved in BQ-induced ROS mediated proliferation. The prolonged activation of ERK1/2 contributes to explain the increased S-phase cell recruitment and to understand the leukemogenic processes associated with exposure to benzene metabolites. Thus, the possible mechanism by which BQ induce HL-60 cells to enter the cell cycle and proliferate is linked to ROS production and its growth promoting effects by specific activation of regulating genes known to be activated by redox mechanisms

Integrating Smart Resources in ROS-based systems to distribute services

Directory of Open Access Journals (Sweden)

Eduardo MUNERA

2017-03-01

Full Text Available Mobile robots need to manage a lot of sensors and actuators using micro-controllers.To do complexes tasks, a highly computation central unit is also needed. In many cases, a robot is a intelligent distributed system formed with a central unit, which manages and distributes several specific tasks to some micro-controller embedded systems onboard.Now these embedded systems are also evolving to more complex systems that are developed not only for executing simple tasks but offering some advanced algorithmsjust as complex data processing, adaptive execution, or fault-tolerance and alarm rising mechanisms. To manage these types of embedded systems a paradigm, calledSmart Resource has been developed. Smart Resources topology has been raised to manage resources which execution relies on a physical embedded hardware. TheseSmart Resources are defined as a list of distributed services that can configure its execution in order to accomplish a context and quality requirements. In order to provide a more general implementation Smart Resources are integrated into the RobotOperating System (ROS. Paper presents a solution based on the Turtlebot platformrunning ROS. The solution shows how robots can make use of all the functions andmechanisms provided by the ROS and the distribution, reliability and adaptability ofthe Smart Resources. In addition it is also addressed the flexibility and scalability ofimplementation by combining real and simulated devices into the same platform

Effects of skin maceration time on the phenolic and sensory characteristics of Bombino Nero rosé wines

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Serafino Suriano

2015-03-01

Full Text Available Rosé wines consumption has reached the highest level in present years and it is still an ongoing trend in several countries. Therefore, the production of rosé wines with improved sensory qualities and colour stability would be greatly appreciated. Today, although rosé wines are no longer considered to be less valuable than red and white ones, anyway, because of the past rosé’s reputation the scientific state of art lacks of specific studies concerning the effects of pre-fermentation maceration times on rosé wines. In this study, different pre fermentation maceration times (3, 6 and 8 h during production of original location certified and guaranteed rosé wine from Bombino Nero variety (Vitis vinifera L. were investigated. In all wines standard and specific wine chemical parameters, such as polyphenols, anthocyanins, flavonoids, hydroxycinnamoyl tartaric acids, volatile compounds and colour parameters were determined. A sensory descriptive analysis together with chemical analyses performed revealed that the maceration time significantly affected the aroma, the flavour and the colour of wines. The results showed that, although a longer maceration time is positively correlated to the colour stability of wine over time, however, a lengthener of the maceration is not favourable to enrich the wine with pleasant fruity and flowery aroma compounds, as both the gas chromatography and the sensory analyses showed. It was decided to perform the experimental winemaking processes in an actual winery instead of a laboratory in order to develop a practical winemaking management procedure directly usable for wine producers. The results obtained contribute to improve the knowledge about the importance of selecting the winemaking technique in order to elaborate high quality rosé wines.

ROS generation and MAPKs activation contribute to the Ni-induced testosterone synthesis disturbance in rat Leydig cells.

Science.gov (United States)

Han, Aijie; Zou, Lingyue; Gan, Xiaoqin; Li, Yu; Liu, Fangfang; Chang, Xuhong; Zhang, Xiaotian; Tian, Minmin; Li, Sheng; Su, Li; Sun, Yingbiao

2018-06-15

Nickel (Ni) can disorder testosterone synthesis in rat Leydig cells, whereas the mechanisms remain unclear. The aim of this study was to investigate the role of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) in Ni-induced disturbance of testosterone synthesis in rat Leydig cells. The testosterone production and ROS levels were detected in Leydig cells. The mRNA and protein levels of testosterone synthetase, including StAR, CYP11A1, 3β-HSD, CYP17A1 and 17β-HSD, were determined. Effects of Ni on the ERK1/2, p38 and JNK MAPKs were also investigated. The results showed that Ni triggered ROS generation, consequently resulted in the decrease of testosterone synthetase expression and testosterone production in Leydig cells, which were then attenuated by ROS scavengers of N-acetylcysteine (NAC) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), indicating that ROS are involved in the Ni-induced testosterone biosynthesis disturbance. Meanwhile Ni activated the ERK1/2, p38 and JNK MAPKs. Furthermore, Ni-inhibited testosterone synthetase expression levels and testosterone secretion were all alleviated by co-treatment with MAPK specific inhibitors (U0126 and SB203580, respectively), implying that Ni inhibited testosterone synthesis through activating ERK1/2 and p38 MAPK signal pathways in Leydig cells. In conclusion, these findings suggest that Ni causes testosterone synthesis disorder, partly, via ROS and MAPK signal pathways. Copyright © 2018 Elsevier B.V. All rights reserved.

Butyrate-Loaded Chitosan/Hyaluronan Nanoparticles: A Suitable Tool for Sustained Inhibition of ROS Release by Activated Neutrophils

DEFF Research Database (Denmark)

Sacco, Pasquale; Decleva, Eva; Tentor, Fabio

2017-01-01

that butyrate inhibits neutrophil ROS release in a dose and time-dependent fashion. Given the short half-life of butyrate, chitosan/hyaluronan nanoparticles are next designed and developed as controlled release carriers able to provide cells with a long-lasting supply of this SCFA. Notably, while the inhibition...... of neutrophil ROS production by free butyrate declines over time, that of butyrate-loaded chitosan/hyaluronan nanoparticles (B-NPs) is sustained. Additional valuable features of these nanoparticles are inherent ROS scavenger activity, resistance to cell internalization, and mucoadhesiveness. B-NPs appear...

Generation of reactive oxygen species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate

International Nuclear Information System (INIS)

Arana, Lide; Gangoiti, Patricia; Ouro, Alberto; Rivera, Io-Guané; Ordoñez, Marta; Trueba, Miguel; Lankalapalli, Ravi S.; Bittman, Robert; Gomez-Muñoz, Antonio

2012-01-01

We previously demonstrated that ceramide 1-phosphate (C1P) is mitogenic for fibroblasts and macrophages. However, the mechanisms involved in this action were only partially described. Here, we demonstrate that C1P stimulates reactive oxygen species (ROS) formation in primary bone marrow-derived macrophages, and that ROS are required for the mitogenic effect of C1P. ROS production was dependent upon prior activation of NADPH oxidase by C1P, which was determined by measuring phosphorylation of the p40phox subunit and translocation of p47phox from the cytosol to the plasma membrane. In addition, C1P activated cytosolic calcium-dependent phospholipase A 2 and protein kinase C-α, and NADPH oxidase activation was blocked by selective inhibitors of these enzymes. These inhibitors, and inhibitors of ROS production, blocked the mitogenic effect of C1P. By using BHNB-C1P (a photolabile caged-C1P analog), we demonstrate that all of these C1P actions are caused by intracellular C1P. It can be concluded that the enzyme responsible for C1P-stimulated ROS generation in bone marrow-derived macrophages is NADPH oxidase, and that this enzyme is downstream of PKC-α and cPLA 2 -α in this pathway. -- Highlights: ► Ceramide 1-phosphate (C1P) stimulates reactive oxygen species (ROS) formation. ► The enzyme responsible for ROS generation by C1P in macrophages is NADPH oxidase. ► NADPH oxidase lies downstream of cPLA 2 -α and PKC-α in this pathway. ► ROS generation is essential for the stimulation of macrophage proliferation by C1P.

Professional burnout in European young oncologists: results of the European Society for Medical Oncology (ESMO) Young Oncologists Committee Burnout Survey.

Science.gov (United States)

Banerjee, S; Califano, R; Corral, J; de Azambuja, E; De Mattos-Arruda, L; Guarneri, V; Hutka, M; Jordan, K; Martinelli, E; Mountzios, G; Ozturk, M A; Petrova, M; Postel-Vinay, S; Preusser, M; Qvortrup, C; Volkov, M N M; Tabernero, J; Olmos, D; Strijbos, M H

2017-07-01

Burnout in health care professionals could have serious negative consequences on quality of patient care, professional satisfaction and personal life. Our aim was to investigate the burnout prevalence, work and lifestyle factors potentially affecting burnout amongst European oncologists ≤40 (YOs). A survey was conducted using the validated Maslach Burnout Inventory (MBI) and additional questions exploring work/lifestyle factors. Statistical analyses were carried out to identify factors associated with burnout. Total of 737 surveys (all ages) were collected from 41 European countries. Countries were divided into six regions. Results from 595 (81%) YOs were included (81% medical oncologists; 52% trainees, 62% women). Seventy-one percent of YOs showed evidence of burnout (burnout subdomains: depersonalization 50%; emotional exhaustion 45; low accomplishment 35%). Twenty-two percent requested support for burnout during training and 74% reported no hospital access to support services. Burnout rates were significantly different across Europe (P women (60% versus 45% P = 0.0001) and low accomplishment was highest in the 26-30 age group (P balance, access to support services, living alone and inadequate vacation time remained independent burnout factors (P balance, access to support services and adequate vacation time may reduce burnout levels. Raising awareness, support and interventional research are needed. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Particle-bound reactive oxygen species (PB-ROS) emissions and formation pathways in residential wood smoke under different combustion and aging conditions

Science.gov (United States)

Zhou, Jun; Zotter, Peter; Bruns, Emily A.; Stefenelli, Giulia; Bhattu, Deepika; Brown, Samuel; Bertrand, Amelie; Marchand, Nicolas; Lamkaddam, Houssni; Slowik, Jay G.; Prévôt, André S. H.; Baltensperger, Urs; Nussbaumer, Thomas; El-Haddad, Imad; Dommen, Josef

2018-05-01

Wood combustion emissions can induce oxidative stress in the human respiratory tract by reactive oxygen species (ROS) in the aerosol particles, which are emitted either directly or formed through oxidation in the atmosphere. To improve our understanding of the particle-bound ROS (PB-ROS) generation potential of wood combustion emissions, a suite of smog chamber (SC) and potential aerosol mass (PAM) chamber experiments were conducted under well-determined conditions for different combustion devices and technologies, different fuel types, operation methods, combustion regimes, combustion phases, and aging conditions. The PB-ROS content and the chemical properties of the aerosols were quantified by a novel ROS analyzer using the DCFH (2',7'-dichlorofluorescin) assay and a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). For all eight combustion devices tested, primary PB-ROS concentrations substantially increased upon aging. The level of primary and aged PB-ROS emission factors (EFROS) were dominated by the combustion device (within different combustion technologies) and to a greater extent by the combustion regimes: the variability within one device was much higher than the variability of EFROS from different devices. Aged EFROS under bad combustion conditions were ˜ 2-80 times higher than under optimum combustion conditions. EFROS from automatically operated combustion devices were on average 1 order of magnitude lower than those from manually operated devices, which indicates that automatic combustion devices operated at optimum conditions to achieve near-complete combustion should be employed to minimize PB-ROS emissions. The use of an electrostatic precipitator decreased the primary and aged ROS emissions by a factor of ˜ 1.5 which is however still within the burn-to-burn variability. The parameters controlling the PB-ROS formation in secondary organic aerosol were investigated by employing a regression model, including the fractions of

Role of ROS in Aβ42 Mediated Activation of Cerebral Endothelial Cells

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Andrey Tsoy

2014-12-01

Full Text Available Introduction. There is substantial evidence that the deposition of aggregated amyloid-beta peptide (Aβ in brain parenchyma and brain vessels is the main cause of neuronal dysfunction and death in Alzheimer’s disease (AD. Aβ exhibits multiple cytotoxic effects on neurons and glial cells and causes dysfunction of the blood brain barrier (BBB. In AD brains, an increased deposition of Aβ in the cerebral vasculature has been found to be correlated with increased transmigration of blood-borne inflammatory cells and neurovascular inflammation. However, regulatory mediators of these processes remain to be elucidated. In this study, we examined the role of ROS in actin polymerization and expression of adhesion molecules (P-selectin on the surface of the cerebral endothelial cells (CECs that are activated by Aβ42.Materials and methods. Mouse BEnd3 line (ATCC was used in this research. BEnd3 cells respond to Aβ treatment similarly to human primary CECs and are a common model to investigate CECs’ function. We used immortalized bEnd3 cells as the following: controls; cells incubated with Aβ42 for 10, 30, and 60 minutes; cells incubated with 30 mM of antioxidant N-acetylcysteine (NAC for 1 hr; and, cells pre-treated with NAC followed by Aβ42 exposure. We measured DHE fluorescence to investigate intracellular ROS production. Immunofluorescent microscopy of anti-P-selectin and oregon green phalloidin was used to quantify the surface P-selectin expression and actin polymerization, and Western blot analysis was used to analyze total P-selectin expression.Results. The results of this study have demonstrated a significant time-dependent ROS accumulation after 10 minutes, 30 minutes, and 60 minutes of Aβ42 treatment, while Aβ42 stimulated ROS production in CECs was attenuated by pre-treatment with the NAC antioxidant. We also found that Aβ42 increased P-selectin fluorescence at the surface of bEnd3 cells in a time dependent manner in parallel to ROS

Attitudes of Oncologists, Oncology Nurses, and Patients from a Women's Clinic Regarding Medical Decision Making for Older and Younger Breast Cancer Patients.

Science.gov (United States)

Beisecker, Analee E.; And Others

1994-01-01

Administered Beisecker Locus of Authority in Decision Making: Breast Cancer survey to 67 oncologists, 94 oncology nurses, and 288 patients from women's clinic. All groups believed that physicians should have dominant role in decision making. Nurses felt that patients should have more input than patients or physicians felt they should. Physicians…

ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function

International Nuclear Information System (INIS)

Pi Jingbo; Zhang Qiang; Fu Jingqi; Woods, Courtney G.; Hou Yongyong; Corkey, Barbara E.; Collins, Sheila; Andersen, Melvin E.

2010-01-01

This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H 2 O 2 , act as metabolic signaling molecules for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Particular emphasis is placed on the potential inhibitory role of endogenous antioxidants, which rise in response to oxidative stress, in glucose-triggered ROS and GSIS. We propose that cellular adaptive response to oxidative stress challenge, such as nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant induction, plays paradoxical roles in pancreatic beta-cell function. On the one hand, induction of antioxidant enzymes protects beta-cells from oxidative damage and possible cell death, thus minimizing oxidative damage-related impairment of insulin secretion. On the other hand, the induction of antioxidant enzymes by Nrf2 activation blunts glucose-triggered ROS signaling, thus resulting in reduced GSIS. These two premises are potentially relevant to impairment of beta-cells occurring in the late and early stage of Type 2 diabetes, respectively. In addition, we summarized our recent findings that persistent oxidative stress due to absence of uncoupling protein 2 activates cellular adaptive response which is associated with impaired pancreatic beta-cell function.

Human Leukemic Cells performing Oxidative Phosphorylation (OXPHOS Generate an Antioxidant Response Independently of Reactive Oxygen species (ROS Production

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Abrar Ul Haq Khan

2016-01-01

Full Text Available Tumor cell metabolism is altered during leukemogenesis. Cells performing oxidative phosphorylation (OXPHOS generate reactive oxygen species (ROS through mitochondrial activity. To limit the deleterious effects of excess ROS, certain gene promoters contain antioxidant response elements (ARE, e.g. the genes NQO-1 and HO-1. ROS induces conformational changes in KEAP1 and releases NRF2, which activates AREs. We show in vitro and in vivo that OXPHOS induces, both in primary leukemic cells and cell lines, de novo expression of NQO-1 and HO-1 and also the MAPK ERK5 and decreases KEAP1 mRNA. ERK5 activates the transcription factor MEF2, which binds to the promoter of the miR-23a–27a–24-2 cluster. Newly generated miR-23a destabilizes KEAP1 mRNA by binding to its 3′UTR. Lower KEAP1 levels increase the basal expression of the NRF2-dependent genes NQO-1 and HO-1. Hence, leukemic cells performing OXPHOS, independently of de novo ROS production, generate an antioxidant response to protect themselves from ROS.

Piroxicam, a traditional non-steroidal anti-inflammatory drug (NSAID) causes apoptosis by ROS mediated Akt activation.

Science.gov (United States)

Rai, Neha; Sarkar, Munna; Raha, Sanghamitra

2015-12-01

Piroxicam (Px) belongs to the oxicam group of the non-steroidal anti-inflammatory drugs (NSAIDs) and have been shown to exert chemopreventive and chemotherapeutic effects in animal models and cultured animal cells. However, little is known about the mode of action of Px and its cellular targets. We explored the role of Px, in triggering apoptosis and examined the involvement of upstream cellular mechanisms in apoptosis induction by Px. Our studies with human breast cancer cells MCF-7 show that Px induces reactive oxygen species (ROS) generation along with apoptotic cell death. ROS release lead to Akt activation. On evaluation it became evident that ROS mediated apoptosis induction was due to Akt activation (hyper phosphorylation). Silencing the expression of Akt using siRNA and a specific Akt inhibitor, triciribine further confirmed the findings. However Px failed to cause ROS generation, cell death or Akt phosphorylation in another human breast cancer cells MDA-MB-231 which is estrogen receptor negative and more aggressive compared to MCF-7 cells. This suggests that Px has cell type specific effects. Thus we revealed for the first time that Px can induce apoptosis by ROS mediated Akt hyperphosphorylation/activation. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Incorporació de funcions a la plataforma robòtica RosPiBot

OpenAIRE

Fernández Vuelta, Adrián

2015-01-01

RosPiBot és una plataforma robòtica de quatre rodes que va sorgir de la restauració del robot Wifibot en un projecte recent. Es caracteritza per la seva capacitat d’adaptació a múltiples terrenys. En l’actual projecte, en primer lloc es presenta el moviment del robot i el comportament dels sensors que seran necessaris en tasques de localització. En segon lloc, es mostra la incorporació de ROS, un marc de treball àmpliament emprat en robòtica, juntament amb el desenvolupament...

The WOPR Protein Ros1 Is a Master Regulator of Sporogenesis and Late Effector Gene Expression in the Maize Pathogen Ustilago maydis.

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Marie Tollot

2016-06-01

Full Text Available The biotrophic basidiomycete fungus Ustilago maydis causes smut disease in maize. Hallmarks of the disease are large tumors that develop on all aerial parts of the host in which dark pigmented teliospores are formed. We have identified a member of the WOPR family of transcription factors, Ros1, as major regulator of spore formation in U. maydis. ros1 expression is induced only late during infection and hence Ros1 is neither involved in plant colonization of dikaryotic fungal hyphae nor in plant tumor formation. However, during late stages of infection Ros1 is essential for fungal karyogamy, massive proliferation of diploid fungal cells and spore formation. Premature expression of ros1 revealed that Ros1 counteracts the b-dependent filamentation program and induces morphological alterations resembling the early steps of sporogenesis. Transcriptional profiling and ChIP-seq analyses uncovered that Ros1 remodels expression of about 30% of all U. maydis genes with 40% of these being direct targets. In total the expression of 80 transcription factor genes is controlled by Ros1. Four of the upregulated transcription factor genes were deleted and two of the mutants were affected in spore development. A large number of b-dependent genes were differentially regulated by Ros1, suggesting substantial changes in this regulatory cascade that controls filamentation and pathogenic development. Interestingly, 128 genes encoding secreted effectors involved in the establishment of biotrophic development were downregulated by Ros1 while a set of 70 "late effectors" was upregulated. These results indicate that Ros1 is a master regulator of late development in U. maydis and show that the biotrophic interaction during sporogenesis involves a drastic shift in expression of the fungal effectome including the downregulation of effectors that are essential during early stages of infection.

Reference: 729 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available eated mutant lines were re-exposed to light, they showed elevated levels of reactive oxygen species (ROS) and a higher mortality... rate compared with wild-type plants. Interestingly, the level of ROS and mortality coul

Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis

Directory of Open Access Journals (Sweden)

Yachun Han

2018-06-01

Full Text Available NLRP3/IL-1β activation via thioredoxin (TRX/thioredoxin-interacting protein (TXNIP following mitochondria ROS (mtROS overproduction plays a key role in inflammation. However, the involvement of this process in tubular damage in the kidneys of patients with diabetic nephropathy (DN is unclear. Here, we demonstrated that mtROS overproduction is accompanied by decreases in TRX expression and TXNIP up-regulation. In addition, we discovered that mtROS overproduction is also associated with increases in NLRP3/IL-1β and TGF-β expression in the kidneys of patients with DN and db/db mice. We reversed these changes in db/db mice by administering a peritoneal injection of MitoQ, an antioxidant targeting mtROS. Similar results were observed in human tubular HK-2 cells subjected to high-glucose (HG conditions and treated with MitoQ. Treating HK-2 cells with MitoQ suppressed the dissociation of TRX from TXNIP and subsequently blocked the interaction between TXNIP and NLRP3, leading to the inhibition of NLRP3 inflammasome activation and IL-1β maturation. The effects of MitoQ were enhanced by pretreatment with TXNIP siRNA and abolished by pretreatment with monosodium urate (MSU and TRX siRNA in vitro. These results suggest that mitochondrial ROS-TXNIP/NLRP3/IL-1β axis activation is responsible for tubular oxidative injury, which can be ameliorated by MitoQ via the inhibition of mtROS overproduction. Keywords: Diabetic nephropathy, Mitochondria, Reactive oxygen species (ROS, TRX/TXNIP, NLRP3 inflammasome, MitoQ

Regional variation in identified cancer care needs of early-career oncologists in China, India, and Pakistan.

Science.gov (United States)

Lyerly, H Kim; Fawzy, Maria R; Aziz, Zeba; Nair, Reena; Pramesh, C S; Parmar, Vani; Parikh, Purvish M; Jamal, Rozmin; Irumnaz, Azizunissa; Ren, Jun; Stockler, Martin R; Abernethy, Amy P

2015-05-01

Cancer incidence and mortality is increasing in the developing world. Inequities between low-, middle-, and high-income countries affect disease burden and the infrastructure needs in response to cancer. We surveyed early-career oncologists attending workshops in clinical research in three countries with emerging economies about their perception of the evolving cancer burden. A cross-sectional survey questionnaire was distributed at clinical trial concept development workshops held in Beijing, Lahore, Karachi, and Mumbai at major hospitals to acquire information regarding home-country health conditions and needs. A total of 100 respondents participated in the workshops held at major hospitals in the region (India = 29, China = 25, Pakistan = 42, and other = 4). Expected consensus on many issues (e.g., emergence of cancer as a significant health issue) was balanced with significant variation in priorities, opportunities, and challenges. Chinese respondents prioritized improvements in cancer-specific care and palliative care, Indian respondents favored improved cancer detection and advancing research in cancer care, and Pakistani respondents prioritized awareness of cancer and improvements in disease detection and cancer care research. For all, the most frequently cited opportunity was help in improving professional cancer education and training. Predominantly early-career oncologists attending clinical research workshops (in China, India, and Pakistan) identified needs for increasing clinical cancer research, professional education, and public awareness of cancer. Decision makers supporting efforts to reduce the burden of cancer worldwide will need to factor the specific needs and aspirations of health care providers in their country in prioritizing health policies and budgets. ©AlphaMed Press.

Effect of prostate-specific membrane antigen positron emission tomography on the decision-making of radiation oncologists

International Nuclear Information System (INIS)

Shakespeare, Thomas P.

2015-01-01

Positron emission tomography (PET) imaging is routinely used in many cancer types, although is not yet a standard modality for prostate carcinoma. Prostate-specific membrane antigen (PSMA) PET is a promising new modality for staging prostate cancer, with recent studies showing potential advantages over traditional computed tomography (CT), magnetic resonance imaging (MRI) and nuclear medicine bone scan imaging. However, the impact of PSMA PET on the decision-making of radiation oncologists and outcomes after radiotherapy is yet to be determined. Our aim was to determine the impact of PSMA PET on a radiation oncologist’s clinical practice. Patients in a radiation oncology clinic who underwent PSMA PET were prospectively recorded in an electronic oncology record. Patient demographics, outcomes of imaging, and impact on decision-making were evaluated. Fifty-four patients underwent PSMA PET between January and May 2015. The major reasons for undergoing PET included staging before definitive (14.8 %) or post-prostatectomy (33.3 %) radiotherapy, and investigation of PSA failures following definitive (16.7 %) or post-prostatectomy (33.3 %) radiotherapy. In 46.3 % of patients PSMA was positive after negative traditional imaging, in 9.3 % PSMA was positive after equivocal imaging, and in 13.0 % PSMA was negative after equivocal imaging. PSMA PET changed radiotherapy management in 46.3 % of cases, and hormone therapy in 33.3 % of patients, with an overall change in decision-making in 53.7 % of patients. PSMA PET has the potential to significantly alter the decision-making of radiation oncologists, and may become a valuable imaging tool in the future

Academic and Resident Radiation Oncologists' Attitudes and Intentions Regarding Radiation Therapy near the End of Life.

Science.gov (United States)

Lloyd, Shane; Dosoretz, Arie P; Yu, James B; Evans, Suzanne B; Decker, Roy H

2016-02-01

There has been increasing scrutiny about cancer treatment for patients very near the end of life (EoL), yet a substantial number receive palliative radiation therapy (RT) in this setting. Our aim was to document the attitudes and intentions of thought leaders and trainees in giving RT near the EoL. We distributed an anonymous survey to 473 radiation oncologists and residents. The survey examined the clinical and psychosocial factors considered as well as intentions and expectations in the delivery of RT near the EoL. Factors surrounding unfinished treatment courses, and the formative factors that shape opinions about RT at the EoL were also explored. We received 139 responses (29%). Eighty-nine percent of respondents worked at academic institutions. The factors that respondents most often consider very or extremely important to offer RT near the EoL were the preference of the patient to be treated (94%), the ability to tolerate treatment (88%), and palliative intent (70%). After instances when their patients were unable to complete treatment near the EoL, 42% of respondents said they would prescribe a shorter treatment the next time they see a similar patient. Personal experience (71%) was most often listed as very or extremely important in shaping their opinions about RT near the EoL. Survey respondents, 89% of whom were academic radiation oncologists, have a positive view of palliative RT near the EoL. They favor shorter fractionation for patients near the EoL. Personal experience is most important in shaping practices and attitudes.

Rhizobium leguminosarum bv. trifolii rosR is required for interaction with clover, biofilm formation and adaptation to the environment

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Piersiak Tomasz

2010-11-01

Full Text Available Abstract Background Rhizobium leguminosarum bv. trifolii is a symbiotic nitrogen-fixing bacterium that elicits nodules on roots of host plants Trifolium spp. Bacterial surface polysaccharides are crucial for establishment of a successful symbiosis with legumes that form indeterminate-type nodules, such as Trifolium, Pisum, Vicia, and Medicago spp. and aid the bacterium in withstanding osmotic and other environmental stresses. Recently, the R. leguminosarum bv. trifolii RosR regulatory protein which controls exopolysaccharide production has been identified and characterized. Results In this work, we extend our earlier studies to the characterization of rosR mutants which exhibit pleiotropic phenotypes. The mutants produce three times less exopolysaccharide than the wild type, and the low-molecular-weight fraction in that polymer is greatly reduced. Mutation in rosR also results in quantitative alterations in the polysaccharide constituent of lipopolysaccharide. The rosR mutants are more sensitive to surface-active detergents, antibiotics of the beta-lactam group and some osmolytes, indicating changes in the bacterial membranes. In addition, the rosR mutants exhibit significant decrease in motility and form a biofilm on plastic surfaces, which differs significantly in depth, architecture, and bacterial viability from that of the wild type. The most striking effect of rosR mutation is the considerably decreased attachment and colonization of root hairs, indicating that the mutation affects the first stage of the invasion process. Infection threads initiate at a drastically reduced rate and frequently abort before they reach the base of root hairs. Although these mutants form nodules on clover, they are unable to fix nitrogen and are outcompeted by the wild type in mixed inoculations, demonstrating that functional rosR is important for competitive nodulation. Conclusions This report demonstrates the significant role RosR regulatory protein plays in

Reaction-based small-molecule fluorescent probes for dynamic detection of ROS and transient redox changes in living cells and small animals.

Science.gov (United States)

Lü, Rui

2017-09-01

Dynamic detection of transient redox changes in living cells and animals has broad implications for human health and disease diagnosis, because intracellular redox homeostasis regulated by reactive oxygen species (ROS) plays important role in cell functions, normal physiological functions and some serious human diseases (e.g., cancer, Alzheimer's disease, diabetes, etc.) usually have close relationship with the intracellular redox status. Small-molecule ROS-responsive fluorescent probes can act as powerful tools for dynamic detection of ROS and redox changes in living cells and animals through fluorescence imaging techniques; and great advances have been achieved recently in the design and synthesis of small-molecule ROS-responsive fluorescent probes. This article highlights up-to-date achievements in designing and using the reaction-based small-molecule fluorescent probes (with high sensitivity and selectivity to ROS and redox cycles) in the dynamic detection of ROS and transient redox changes in living cells and animals through fluorescence imaging. Copyright © 2017. Published by Elsevier Ltd.

Ros-gazebo. una valiosa Herramienta de Vanguardia para el Desarrollo de la Robótica

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Cristian Camilo Cuevas Castañeda

2016-03-01

Full Text Available El Sistema Operativo Robótico – ROS (de aquí en adelante ROS representa un significativo avance en la tecnología robótica, ya que constituye un verdadero modelo colaborativo de desarrollo, abierto al público en general y con una gama de posibilidades aún por descubrir. ROS permite contar con estructuras ya diseña- das y programadas que luego se pueden modificar, evitando, de esta manera, comenzar de cero con cada diseño y superando la pérdida de tiempo inherente a la construcción de algoritmos de piezas comunes, como brazos y ruedas, entre otras. Tal plataforma se complementa con las herramientas de Rviz y Gazebo, que brindan simulaciones 3D del modelo robótico diseñado.

Data from a professional society placement service as a measure of the employment market for radiation oncologists

International Nuclear Information System (INIS)

Bhargavan, Mythreyi; Sunshine, Jonathan H.; Schepps, Barbara

2002-01-01

Purpose: To aid in understanding the employment market for radiation oncologists, we present annual data for 1991 to 2000 from the American College of Radiology's placement service, the Professional Bureau. This data series is twice as long as any previously available. Secondarily, we compare these data with other data on the employment market. Methods and Materials: The trends in job listings, job seekers, and listings per seeker in the Bureau are tabulated and graphed. We calculate correlations and graph relationships between the last of these and measures of the job market calculated from annual surveys. Results: Bureau data show listings per job seeker declined from 0.53 in 1991 to a nadir of 0.30 in 1995 and then recovered to 1.48 in 2000. Bureau listings and job seekers, each considered separately, show a similar pattern of job market decline and then eventual recovery to better than the 1991 situation. Bureau listings per job seeker correlate 0.895 with a survey-derived index of program directors' perceptions of the job market, but statistical significance is limited (p=0.04), because very few years of survey data are available. Conclusions: The employment market for radiation oncologists weakened in the first half of the 1990s, as had been widely reported; we present the first systematic data showing this. Data from a professional society placement service provide useful and inexpensive information on the employment market

An Innovative Tool for Intraoperative Electron Beam Radiotherapy Simulation and Planning: Description and Initial Evaluation by Radiation Oncologists

Energy Technology Data Exchange (ETDEWEB)

Pascau, Javier, E-mail: jpascau@mce.hggm.es [Unidad de Medicina y Cirugia Experimental, Hospital General Universitario Gregorio Maranon, Madrid (Spain); Departamento de Bioingenieria e Ingenieria Aeroespacial, Universidad Carlos III de Madrid, Madrid (Spain); Santos Miranda, Juan Antonio [Servicio de Oncologia Radioterapica, Hospital General Universitario Gregorio Maranon, Madrid (Spain); Facultad de Medicina, Universidad Complutense de Madrid, Madrid (Spain); Calvo, Felipe A. [Servicio de Oncologia Radioterapica, Hospital General Universitario Gregorio Maranon, Madrid (Spain); Facultad de Medicina, Universidad Complutense de Madrid, Madrid (Spain); Departamento de Oncologia, Hospital General Universitario Gregorio Maranon, Madrid (Spain); Bouche, Ana; Morillo, Virgina [Consorcio Hospitalario Provincial de Castellon, Castellon (Spain); Gonzalez-San Segundo, Carmen [Servicio de Oncologia Radioterapica, Hospital General Universitario Gregorio Maranon, Madrid (Spain); Facultad de Medicina, Universidad Complutense de Madrid, Madrid (Spain); Ferrer, Carlos; Lopez Tarjuelo, Juan [Consorcio Hospitalario Provincial de Castellon, Castellon (Spain); and others

2012-06-01

Purpose: Intraoperative electron beam radiation therapy (IOERT) involves a modified strategy of conventional radiation therapy and surgery. The lack of specific planning tools limits the spread of this technique. The purpose of the present study is to describe a new simulation and planning tool and its initial evaluation by clinical users. Methods and Materials: The tool works on a preoperative computed tomography scan. A physician contours regions to be treated and protected and simulates applicator positioning, calculating isodoses and the corresponding dose-volume histograms depending on the selected electron energy. Three radiation oncologists evaluated data from 15 IOERT patients, including different tumor locations. Segmentation masks, applicator positions, and treatment parameters were compared. Results: High parameter agreement was found in the following cases: three breast and three rectal cancer, retroperitoneal sarcoma, and rectal and ovary monotopic recurrences. All radiation oncologists performed similar segmentations of tumors and high-risk areas. The average applicator position difference was 1.2 {+-} 0.95 cm. The remaining cancer sites showed higher deviations because of differences in the criteria for segmenting high-risk areas (one rectal, one pancreas) and different surgical access simulated (two rectal, one Ewing sarcoma). Conclusions: The results show that this new tool can be used to simulate IOERT cases involving different anatomic locations, and that preplanning has to be carried out with specialized surgical input.

European contribution to the study of ROS : A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)

NARCIS (Netherlands)

Egea, Javier; Fabregat, Isabel; Frapart, Yves M; Ghezzi, Pietro; Görlach, Agnes; Kietzmann, Thomas; Kubaichuk, Kateryna; Knaus, Ulla G; Lopez, Manuela G; Olaso-Gonzalez, Gloria; Petry, Andreas; Schulz, Rainer; Vina, Jose; Winyard, Paul J; Abbas, Kahina; Ademowo, Opeyemi S; Afonso, Catarina B; Andreadou, Ioanna; Antelmann, Haike; Antunes, Fernando; Aslan, Mutay; Bachschmid, Markus M; Barbosa, Rui M; Belousov, Vsevolod; Berndt, Carsten; Bernlohr, David; Bertrán, Esther; Bindoli, Alberto; Bottari, Serge P; Brito, Paula M; Carrara, Guia; Casas, Ana I; Chatzi, Afroditi; Chondrogianni, Niki; Conrad, Marcus; Cooke, Marcus S; Costa, João G; Cuadrado, Antonio; My-Chan Dang, Pham; De Smet, Barbara; Debelec-Butuner, Bilge; Dias, Irundika H K; Dunn, Joe Dan; Edson, Amanda J; El Assar, Mariam; El-Benna, Jamel; Ferdinandy, Péter; Fernandes, Ana S; Fladmark, Kari E; Förstermann, Ulrich; Giniatullin, Rashid; Giricz, Zoltán; Görbe, Anikó; Griffiths, Helen L; Hampl, Vaclav; Hanf, Alina; Herget, Jan; Hernansanz-Agustín, Pablo; Hillion, Melanie; Huang, Jingjing; Ilikay, Serap; Jansen-Dürr, Pidder; Jaquet, Vincent; Joles, Jaap A; Kalyanaraman, Balaraman; Kaminskyy, Danylo; Karbaschi, Mahsa; Kleanthous, Marina; Klotz, Lars-Oliver; Korac, Bato; Korkmaz, Kemal Sami; Koziel, Rafal; Kračun, Damir; Krause, Karl-Heinz; Křen, Vladimír; Krieg, Thomas; Laranjinha, João; Lazou, Antigone; Li, Huige; Martínez-Ruiz, Antonio; Matsui, Reiko; McBean, Gethin J; Meredith, Stuart P; Messens, Joris; Miguel, Verónica; Mikhed, Yuliya; Milisav, Irina; Milković, Lidija; Miranda-Vizuete, Antonio; Mojović, Miloš; Monsalve, María; Mouthuy, Pierre-Alexis; Mulvey, John; Münzel, Thomas; Muzykantov, Vladimir; Nguyen, Isabel T N; Oelze, Matthias; Oliveira, Nuno G; Palmeira, Carlos M; Papaevgeniou, Nikoletta; Pavićević, Aleksandra; Pedre, Brandán; Peyrot, Fabienne; Phylactides, Marios; Pircalabioru, Gratiela G; Pitt, Andrew R; Poulsen, Henrik E; Prieto, Ignacio; Rigobello, Maria Pia; Robledinos-Antón, Natalia; Rodríguez-Mañas, Leocadio; Rolo, Anabela P; Rousset, Francis; Ruskovska, Tatjana; Saraiva, Nuno; Sasson, Shlomo; Schröder, Katrin; Semen, Khrystyna; Seredenina, Tamara; Shakirzyanova, Anastasia; Smith, Geoffrey L; Soldati, Thierry; Sousa, Bebiana C; Spickett, Corinne M; Stancic, Ana; Stasia, Marie José; Steinbrenner, Holger; Stepanić, Višnja; Steven, Sebastian; Tokatlidis, Kostas; Tuncay, Erkan; Turan, Belma; Ursini, Fulvio; Vacek, Jan; Vajnerova, Olga; Valentová, Kateřina; Van Breusegem, Frank; Varisli, Lokman; Veal, Elizabeth A; Yalçın, A Suha; Yelisyeyeva, Olha; Žarković, Neven; Zatloukalová, Martina; Zielonka, Jacek; Touyz, Rhian M; Papapetropoulos, Andreas; Grune, Tilman; Lamas, Santiago; Schmidt, Harald H H W; Di Lisa, Fabio; Daiber, Andreas

2017-01-01

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better

Supporting patients in obtaining and oncologists in providing evidence-based health-related quality of life information prior to and after esophageal cancer surgery

NARCIS (Netherlands)

Jacobs, M.

2015-01-01

The overall aim of this thesis was to support patients in obtaining and oncologists in providing evidence-based HRQL data prior to and following esophageal cancer surgery. This thesis is divided in two parts. In Part I, we addressed the information needs of esophageal cancer patients prior to and

Skin Aging-Dependent Activation of the PI3K Signaling Pathway via Downregulation of PTEN Increases Intracellular ROS in Human Dermal Fibroblasts

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Eun-Mi Noh

2016-01-01

Full Text Available Reactive oxygen species (ROS play a major role in both chronological aging and photoaging. ROS induce skin aging through their damaging effect on cellular constituents. However, the origins of ROS have not been fully elucidated. We investigated that ROS generation of replicative senescent fibroblasts is generated by the modulation of phosphatidylinositol 3,4,5-triphosphate (PIP3 metabolism. Reduction of the PTEN protein, which dephosphorylates PIP3, was responsible for maintaining a high level of PIP3 in replicative cells and consequently mediated the activation of the phosphatidylinositol-3-OH kinase (PI3K/Akt pathway. Increased ROS production was blocked by inhibition of PI3K or protein kinase C (PKC or by NADPH oxidase activating in replicative senescent cells. These data indicate that the signal pathway to ROS generation in replicative aged skin cells can be stimulated by reduced PTEN level. Our results provide new insights into skin aging-associated modification of the PI3K/NADPH oxidase signaling pathway and its relationship with a skin aging-dependent increase of ROS in human dermal fibroblasts.

Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells.

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Zeng, Wei; Xiao, Tao; Cai, Anlie; Cai, Weiliang; Liu, Huanhuan; Liu, Jingling; Li, Jie; Tan, Miduo; Xie, Li; Liu, Ying; Yang, Xiangcheng; Long, Yi

2017-01-01

Autophagy modulation has been considered a potential therapeutic strategy for human chondrosarcoma, and a previous study indicated that salidroside exhibits significant anti-carcinogenic activity. However, the ability of salidroside to induce autophagy and its role in human chondrosarcoma cell death remains unclear. We exposed SW1353 cells to different concentrations of salidroside (0.5, 1 and 2 mM) for 24 h. RT-PCR, Western-blotting, Immunocytofluorescence, and Luciferase Reporter Assays were used to evaluate whether salidroside activated the TFEB-dependent autophagy. We show that salidroside induced significant apoptosis in the human chondrosarcoma cell line SW1353. In addition, we demonstrate that salidroside-induced an autophagic response in SW1353 cells, as evidenced by the upregulation of LC3-II and downregulation of P62. Moreover, pharmacological or genetic blocking of autophagy enhanced salidroside -induced apoptosis, indicating the cytoprotective role of autophagy in salidroside-treated SW1353 cells. Salidroside also induced TFEB (Ser142) dephosphorylation, subsequently to activated TFEB nuclear translocation and increase of TFEB reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes. Importantly, we found that salidroside triggered the generation of ROS in SW1353 cells. Furthermore, NAC, a ROS scavenger, abrogated the effects of salidroside on TFEB-dependent autophagy. These data demonstrate that salidroside increased TFEB-dependent autophagy by activating ROS signaling pathways in human chondrosarcoma cells. These data also suggest that blocking ROS-TFEB-dependent autophagy to enhance the activity of salidroside warrants further attention in treatment of human chondrosarcoma cells. © 2017 The Author(s). Published by S. Karger AG, Basel.

Generation of ROS mediated by mechanical waves (ultrasound) and its possible applications.

Science.gov (United States)

Duco, Walter; Grosso, Viviana; Zaccari, Daniel; Soltermann, Arnaldo T

2016-10-15

The thermal decomposition of 9,10 diphenylanthracene peroxide (DPAO 2 ) generates DPA and a mix of triplet and singlet molecular oxygen. For DPAO 2 the efficiency to produce singlet molecular oxygen is 0.35. On the other hand, it has shown that many thermal reactions can be carried out through the interaction of molecules with ultrasound. Ultrasound irradiation can create hydrodynamic stress (sonomechanical process), inertial cavitation (pyrolitic process) and long range effects mediated by radicals or ROS. Sonochemical reactions can be originated by pyrolytic like process, shock mechanical waves, thermal reactions and radical and ROS mediated reactions. Sonolysis of pure water can yield hydrogen or hydroxyl radicals and hydrogen peroxide (ROS). When DPAO 2 in 1,4 dioxane solution is treated with 20 or 24kHz and different power intensity the production of molecular singlet oxygen is observed. Specific scavengers like tetracyclone (TC) are used to demonstrate it. The efficiency now is 0.85 showing that the sonochemical process is much more efficient that the thermal one. Another endoperoxide, artemisinin was also studied. Unlike the concept of photosensitizer of photodynamic therapy, in spite of large amount of reported results in literature, the term sonosensitizer and the sonosensitization process are not well defined. We define sonosensitized reaction as one in which a chemical species decompose as consequence of cavitation phenomena producing ROS or other radicals and some other target species does undergo a chemical reaction. The concept could be reach rapidly other peroxides which are now under experimental studies. For artemisinin, an important antimalarian and anticancer drug, was established that ultrasound irradiation increases the effectiveness of the treatment but without any explanation. We show that artemisinin is an endoperoxide and behaves as a sonosensitizer in the sense of our definition. Copyright © 2016 Elsevier Inc. All rights reserved.

Uudised : Fääri ooper Tallinnas. Sigur Ros Tallinnas

Index Scriptorium Estoniae

2008-01-01

10.-12. septembrini mängitakse Tallinnas Kultuurikatlas fääri helilooja Sunleif Rasmusseni ooperit "Hullu mehe aias", lavastajaks Robert Annus. 23. augustil annab Rock Cafés kontserdi Islandi eksperimentaalrocki ansambel Sigur Ros, kes esitleb oma viiendat albumit "Med sud i eyrum vid spilum endalaust" (mida võiks tõlkida "Mängime lõppematult, sumin kõrvus"

Best medical practice: viewpoint of a UK oncologist.

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Stoll, B

1989-01-01

In a clinician's view, best medical practice has two distinct meanings in a tax-funded health system: optimal management as expected by the individual patient; or, the best possible within the economic limits dictated by the society. Based on this viewpoint, this article represents an oncologist's perspective on the meaning of best medical practice in the management of patients suffering from cancer, the extent to which it is achieved in the UK health system, and how far some of the present deficiencies may be overcome. There is urgent need for medical audit in the management of cancer patients in the UK because the traditional clinical freedom of doctors can lead to wide variations in management without corresponding differences in outcome as measured by benefit to the patient. We need consensus by physicians on the guidelines for optimal management of different types of cancer at various stages, both to avoid overtreatment of the individual patient and also to direct scarce resources to their most effective use. Physicians also need to agree on guidelines for giving priority to one patient over another when resources are limited, and such criteria need to be approved by society at large. The public must accept that in a non-explicit rationing system, each individual competes with every other. In the case of even more difficult ethical choices, a multidisciplinary national committee is required to advise on decision-making and its views need to be debated by the general public.

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS

Directory of Open Access Journals (Sweden)

Javier Egea

2017-10-01

Full Text Available The European Cooperation in Science and Technology (COST provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.

Arabidopsis ABI5 plays a role in regulating ROS homeostasis by activating CATALASE 1 transcription in seed germination.

Science.gov (United States)

Bi, Chao; Ma, Yu; Wu, Zhen; Yu, Yong-Tao; Liang, Shan; Lu, Kai; Wang, Xiao-Fang

2017-05-01

It has been known that ABA INSENSITIVE 5 (ABI5) plays a vital role in regulating seed germination. In the present study, we showed that inhibition of the catalase activity with 3-amino-1,2,4-triazole (3-AT) inhibits seed germination of Col-0, abi5 mutants and ABI5-overexpression transgenic lines. Compared with Col-0, the seeds of abi5 mutants showed more sensitive to 3-AT during seed germination, while the seeds of ABI5-overexpression transgenic lines showed more insensitive. H 2 O 2 showed the same effect on seed germination of Col-0, abi5 mutants and ABI5-overexpression transgenic lines as 3-AT. These results suggest that ROS is involved in the seed germination mediated by ABI5. Further, we observed that T-DNA insertion mutants of the three catalase members in Arabidopsis displayed 3-AT-insensitive or -hypersensitive phenotypes during seed germination, suggesting that these catalase members regulate ROS homeostasis in a highly complex way. ABI5 affects reactive oxygen species (ROS) homeostasis by affecting CATALASE expression and catalase activity. Furthermore, we showed that ABI5 directly binds to the CAT1 promoter and activates CAT1 expression. Genetic evidence supports the idea that CAT1 functions downstream of ABI5 in ROS signaling during seed germination. RNA-sequencing analysis indicates that the transcription of the genes involved in ROS metabolic process or genes responsive to ROS stress is impaired in abi5-1 seeds. Additionally, expression changes in some genes correlative to seed germination were showed due to the change in ABI5 expression under 3-AT treatment. Together, all the findings suggest that ABI5 regulates seed germination at least partly by affecting ROS homeostasis.

Oleic, Linoleic and Linolenic Acids Increase ROS Production by Fibroblasts via NADPH Oxidase Activation

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Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

2013-01-01

The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts. PMID:23579616

Oleic, linoleic and linolenic acids increase ros production by fibroblasts via NADPH oxidase activation.

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Elaine Hatanaka

Full Text Available The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47 (phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47 (phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts.

Adherence of Primary Care Physicians to Evidence-Based Recommendations to Reduce Ovarian Cancer Mortality

Science.gov (United States)

Stewart, Sherri L.; Townsend, Julie S.; Puckett, Mary C.; Rim, Sun Hee

2017-01-01

Ovarian cancer is the deadliest gynecologic cancer. Receipt of treatment from a gynecologic oncologist is an evidence-based recommendation to reduce mortality from the disease. We examined knowledge and application of this evidence-based recommendation in primary care physicians as part of CDC gynecologic cancer awareness campaign efforts and discussed results in the context of CDC National Comprehensive Cancer Control Program (NCCCP). We analyzed primary care physician responses to questions about how often they refer patients diagnosed with ovarian cancer to gynecologic oncologists, and reasons for lack of referral. We also analyzed these physicians’ knowledge of tests to help determine whether a gynecologic oncologist is needed for a planned surgery. The survey response rate was 52.2%. A total of 84% of primary care physicians (87% of family/general practitioners, 81% of internists and obstetrician/gynecologists) said they always referred patients to gynecologic oncologists for treatment. Common reasons for not always referring were patient preference or lack of gynecologic oncologists in the practice area. A total of 23% of primary care physicians had heard of the OVA1 test, which helps to determine whether gynecologic oncologist referral is needed. Although referral rates reported here are high, it is not clear whether ovarian cancer patients are actually seeing gynecologic oncologists for care. The NCCCP is undertaking several efforts to assist with this, including education of the recommendation among women and providers and assistance with treatment summaries and patient navigation toward appropriate treatment. Expansion of these efforts to all populations may help improve adherence to recommendations and reduce ovarian cancer mortality. PMID:26978124

Blood meal-derived heme decreases ROS levels in the midgut of Aedes aegypti and allows proliferation of intestinal microbiota.

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Jose Henrique M Oliveira

2011-03-01

Full Text Available The presence of bacteria in the midgut of mosquitoes antagonizes infectious agents, such as Dengue and Plasmodium, acting as a negative factor in the vectorial competence of the mosquito. Therefore, knowledge of the molecular mechanisms involved in the control of midgut microbiota could help in the development of new tools to reduce transmission. We hypothesized that toxic reactive oxygen species (ROS generated by epithelial cells control bacterial growth in the midgut of Aedes aegypti, the vector of Yellow fever and Dengue viruses. We show that ROS are continuously present in the midgut of sugar-fed (SF mosquitoes and a blood-meal immediately decreased ROS through a mechanism involving heme-mediated activation of PKC. This event occurred in parallel with an expansion of gut bacteria. Treatment of sugar-fed mosquitoes with increased concentrations of heme led to a dose dependent decrease in ROS levels and a consequent increase in midgut endogenous bacteria. In addition, gene silencing of dual oxidase (Duox reduced ROS levels and also increased gut flora. Using a model of bacterial oral infection in the gut, we show that the absence of ROS resulted in decreased mosquito resistance to infection, increased midgut epithelial damage, transcriptional modulation of immune-related genes and mortality. As heme is a pro-oxidant molecule released in large amounts upon hemoglobin degradation, oxidative killing of bacteria in the gut would represent a burden to the insect, thereby creating an extra oxidative challenge to the mosquito. We propose that a controlled decrease in ROS levels in the midgut of Aedes aegypti is an adaptation to compensate for the ingestion of heme.

Alanine Enhances Aminoglycosides-Induced ROS Production as Revealed by Proteomic Analysis

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Jin-zhou Ye

2018-01-01

Full Text Available Metabolite-enabled killing of antibiotic-resistant pathogens by antibiotics is an attractive strategy to manage antibiotic resistance. Our previous study demonstrated that alanine or/and glucose increased the killing efficacy of kanamycin on antibiotic-resistant bacteria, whose action is through up-regulating TCA cycle, increasing proton motive force and enhancing antibiotic uptake. Despite the fact that alanine altered several metabolic pathways, other mechanisms could be potentially involved in alanine-mediated kanamycin killing of bacteria which remains to be explored. In the present study, we adopted proteomic approach to analyze the proteome changes induced by exogenous alanine. Our results revealed that the expression of three outer membrane proteins was altered and the deletion of nagE and fadL decreased the intracellular kanamycin concentration, implying their possible roles in mediating kanamycin transport. More importantly, the integrated analysis of proteomic and metabolomic data pointed out that alanine metabolism could connect to riboflavin metabolism that provides the source for reactive oxygen species (ROS production. Functional studies confirmed that alanine treatment together with kanamycin could promote ROS production that in turn potentiates the killing of antibiotic-resistant bacteria. Further investigation showed that alanine repressed the transcription of antioxidant-encoding genes, and alanine metabolism to riboflavin metabolism connected with riboflavin metabolism through TCA cycle, glucogenesis pathway and pentose phosphate pathway. Our results suggest a novel mechanism by which alanine facilitates kanamycin killing of antibiotic-resistant bacteria via promoting ROS production.

Hyperglycemia regulates TXNIP/TRX/ROS axis via p38 MAPK and ERK pathways in pancreatic cancer.

Science.gov (United States)

Li, Wei; Wu, Zheng; Ma, Qingyong; Liu, Jiangbo; Xu, Qinhong; Han, Liang; Duan, Wanxing; Lv, Yunfu; Wang, Fengfei; Reindl, Katie M; Wu, Erxi

2014-01-01

Approximately 85% of pancreatic cancer patients suffer from glucose intolerance or even diabetes because high glucose levels can contribute to oxidative stress which promotes tumor development. As one of the reactive oxygen species (ROS)-regulating factors, thioredoxin-interacting protein (TXNIP), is involved in the maintenance of thioredoxin (TRX)-mediated redox regulation. In this study, we demonstrated that high glucose levels increased the expression of TXNIP in time- and concentration-dependent manners and modulated the activity of TRX and ROS production in pancreatic cancer cells, BxPC-3 and Panc-1. We also found that glucose activated both p38 MAPK and ERK pathways and inhibitors of these pathways impaired the TXNIP/TRX/ROS axis. Knockdown of TXNIP restored TRX activity and decreased ROS production under high glucose conditions. Moreover, we observed that the integrated optical density (IOD) of TXNIP staining as well as the protein and mRNA expression levels of TXNIP were higher in the tumor tissues of pancreatic cancer patients with diabetes. Taken together, these results indicate that hyperglycemia-induced TXNIP expression is involved in diabetes-mediated oxidative stress in pancreatic cancer via p38 MAPK and ERK pathways.

Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling.

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Cao, Yang; Wei, Wei; Zhang, Nan; Yu, Qing; Xu, Wen-Bin; Yu, Wen-Jun; Chen, Guo-Qiang; Wu, Ying-Li; Yan, Hua

2015-04-10

Retinoic acid receptor alpha (RARα) plays an essential role in the regulation of many biological processes, such as hematopoietic cell differentiation, while abnormal RARα function contributes to the pathogenesis of certain diseases including cancers, especially acute promyelocytic leukemia (APL). Recently, oridonin, a natural diterpenoid isolated from Rabdosia rubescens, was demonstrated to regulate RARα by increasing its protein level. However, the underlying molecular mechanism for this action has not been fully elucidated. In the APL cell line, NB4, the effect of oridonin on RARα protein was analyzed by western blot and real-time quantitative RT-PCR analyses. Flow cytometry was performed to detect intracellular levels of reactive oxygen species (ROS). The association between nuclear factor-kappa B (NF-κB) signaling and the effect of oridonin was assessed using specific inhibitors, shRNA gene knockdown, and immunofluorescence assays. In addition, primary leukemia cells were treated with oridonin and analyzed by western blot in this study. RARα possesses transcriptional activity in the presence of its ligand, all-trans retinoic acid (ATRA). Oridonin remarkably stabilized the RARα protein, which retained transcriptional activity. Oridonin also moderately increased intracellular ROS levels, while pretreatment with the ROS scavenger, N-acetyl-l-cysteine (NAC), dramatically abrogated RARα stabilization by oridonin. More intriguingly, direct exposure to low concentrations of H2O2 also increased RARα protein but not mRNA levels, suggesting a role for ROS in oridonin stabilization of RARα protein. Further investigations showed that NAC antagonized oridonin-induced activation of NF-κB signaling, while the NF-κB signaling inhibitor, Bay 11-7082, effectively blocked the oridonin increase in RARα protein levels. In line with this, over-expression of IκΒα (A32/36), a super-repressor form of IκΒα, or NF-κB-p65 knockdown inhibited oridonin or H2O2-induced

Endoplasmic reticulum-derived reactive oxygen species (ROS) is involved in toxicity of cell wall stress to Candida albicans.

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Yu, Qilin; Zhang, Bing; Li, Jianrong; Zhang, Biao; Wang, Honggang; Li, Mingchun

2016-10-01

The cell wall is an important cell structure in both fungi and bacteria, and hence becomes a common antimicrobial target. The cell wall-perturbing agents disrupt synthesis and function of cell wall components, leading to cell wall stress and consequent cell death. However, little is known about the detailed mechanisms by which cell wall stress renders fungal cell death. In this study, we found that ROS scavengers drastically attenuated the antifungal effect of cell wall-perturbing agents to the model fungal pathogen Candida albicans, and these agents caused remarkable ROS accumulation and activation of oxidative stress response (OSR) in this fungus. Interestingly, cell wall stress did not cause mitochondrial dysfunction and elevation of mitochondrial superoxide levels. Furthermore, the iron chelator 2,2'-bipyridyl (BIP) and the hydroxyl radical scavengers could not attenuate cell wall stress-caused growth inhibition and ROS accumulation. However, cell wall stress up-regulated expression of unfold protein response (UPR) genes, enhanced protein secretion and promoted protein folding-related oxidation of Ero1, an important source of ROS production. These results indicated that oxidation of Ero1 in the endoplasmic reticulum (ER), rather than mitochondrial electron transport and Fenton reaction, contributed to cell wall stress-related ROS accumulation and consequent growth inhibition. Our findings uncover a novel link between cell wall integrity (CWI), ER function and ROS production in fungal cells, and shed novel light on development of strategies promoting the antifungal efficacy of cell wall-perturbing agents against fungal infections. Copyright © 2016 Elsevier Inc. All rights reserved.

MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion.

Science.gov (United States)

Park, Woo Hyun; Kim, Suhn Hee

2012-04-01

MG132 as a proteasome inhibitor can induce apoptotic cell death in lung cancer cells. However, little is known about the toxicological cellular effects of MG132 on normal primary lung cells. Here, we investigated the effects of N-acetyl cysteine (NAC) and vitamin C (well known antioxidants) or L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) on MG132-treated human pulmonary fibroblast (HPF) cells in relation to cell death, reactive oxygen species (ROS) and glutathione (GSH). MG132 induced growth inhibition and death in HPF cells, accompanied by the loss of mitochondrial membrane potential (MMP; ∆ψm). MG132 increased ROS levels and GSH-depleted cell numbers in HPF cells. Both antioxidants, NAC and vitamin C, prevented growth inhibition, death and MMP (∆ψm) loss in MG132-treated HPF cells and also attenuated ROS levels in these cells. BSO showed a strong increase in ROS levels in MG132-treated HPF cells and slightly enhanced the growth inhibition, cell death, MMP (∆ψm) loss and GSH depletion. In addition, NAC decreased anonymous ubiquitinated protein levels in MG132-treated HPF cells. Furthermore, superoxide dismutase (SOD) 2, catalase (CTX) and GSH peroxidase (GPX) siRNAs enhanced HPF cell death by MG132, which was not correlated with ROS and GSH level changes. In conclusion, MG132 induced the growth inhibition and death of HPF cells, which were accompanied by increasing ROS levels and GSH depletion. Both NAC and vitamin C attenuated HPF cell death by MG132, whereas BSO slightly enhanced the death.

Protocolo de actuación ante la rosácea en la farmacia comunitaria

Directory of Open Access Journals (Sweden)

Espinosa Suances A

2016-06-01

Full Text Available La rosácea es una dermatosis facial inflamatoria, recidivante y crónica, que con frecuencia demanda consulta en la farmacia comunitaria. Orientado hacia la práctica clínica del farmacéutico comunitario, este artículo revisa y sintetiza los conceptos clásicos y los avances más recientes en la comprensión y el tratamiento de esta enfermedad cutánea. Finalmente, propone un protocolo para la asistencia de pacientes con rosácea en la farmacia comunitaria.

Women with breast cancer report substantially more disease- and treatment-related side or late effects than registered by clinical oncologists: a cross-sectional study of a standard follow-up program in an oncological department.

Science.gov (United States)

Ellegaard, Mai-Britt Bjørklund; Grau, Cai; Zachariae, Robert; Jensen, Anders Bonde

2017-08-01

Follow-up after breast cancer treatment is standard due to the risk of development of new primary cancers and recurrent disease. The aim of the present study was to evaluate a standard follow-up program in an oncological department by assessing: (1) Symptoms or signs of new primary cancer or recurrent disease, (2) Disease- and treatment-related physical and psychosocial side or late effects, and (3) relevant actions by oncology staff. In a cross-sectional study, 194 women who came for follow-up visit after treatment for primary surgery were included. The clinical oncologists registered symptoms and signs of recurrent disease or new primary cancer. Side or late effects were both assessed by patient and the clinical oncologists. Loco-regional or distant signs of recurrent disease were suspected in eight (5%) patients. Further examinations revealed no disease recurrence. Most patients (93%) reported some degree of side or late effects. Statistically significant more side or late effects were reported by the women (average: 6.9) than registered by the clinical oncologists (average: 2.4), p effects were hot flushes (35%), fatigue (32%), and sleep disturbance (31%). None of the scheduled or additional visits resulted in detection of recurrent disease. Furthermore, the majority of patients reported side or late effects. Statistically significant more women reported side or late effects than registered by the clinical oncologists. This suggests the need for rethinking of the follow-up programs with more emphasis upon side or late effects of the treatment.

Sensitivity of the green algae Chlamydomonas reinhardtii to gamma radiation: Photosynthetic performance and ROS formation.

Science.gov (United States)

Gomes, Tânia; Xie, Li; Brede, Dag; Lind, Ole-Christian; Solhaug, Knut Asbjørn; Salbu, Brit; Tollefsen, Knut Erik

2017-02-01

The aquatic environment is continuously exposed to ionizing radiation from both natural and anthropogenic sources, making the characterization of ecological and health risks associated with radiation of large importance. Microalgae represent the main source of biomass production in the aquatic ecosystem, thus becoming a highly relevant biological model to assess the impacts of gamma radiation. However, little information is available on the effects of gamma radiation on microalgal species, making environmental radioprotection of this group of species challenging. In this context, the present study aimed to improve the understanding of the effects and toxic mechanisms of gamma radiation in the unicellular green algae Chlamydomonas reinhardtii focusing on the activity of the photosynthetic apparatus and ROS formation. Algal cells were exposed to gamma radiation (0.49-1677mGy/h) for 6h and chlorophyll fluorescence parameters obtained by PAM fluorometry, while two fluorescent probes carboxy-H 2 DFFDA and DHR 123 were used for the quantification of ROS. The alterations seen in functional parameters of C. reinhardtii PSII after 6h of exposure to gamma radiation showed modifications of PSII energy transfer associated with electron transport and energy dissipation pathways, especially at the higher dose rates used. Results also showed that gamma radiation induced ROS in a dose-dependent manner under both light and dark conditions. The observed decrease in photosynthetic efficiency seems to be connected to the formation of ROS and can potentially lead to oxidative stress and cellular damage in chloroplasts. To our knowledge, this is the first report on changes in several chlorophyll fluorescence parameters associated with photosynthetic performance and ROS formation in microalgae after exposure to gamma radiation. Copyright © 2016 Elsevier B.V. All rights reserved.

Cadmium-induced glutathionylation of actin occurs through a ROS-independent mechanism: Implications for cytoskeletal integrity

Energy Technology Data Exchange (ETDEWEB)

Choong, Grace; Liu, Ying; Xiao, Weiqun; Templeton, Douglas M., E-mail: doug.templeton@utoronto.ca

2013-10-15

Cadmium disrupts the actin cytoskeleton in rat mesangial cells, and we have previously shown that this involves a complex interplay involving activation of kinase signaling, protein translocation, and disruption of focal adhesions. Here we investigate the role that glutathionylation of actin plays in Cd{sup 2+}-associated cytoskeletal reorganization. Low concentrations of Cd{sup 2+} (0.5–2 μM) caused an increase in actin glutathionylation by 6 h, whereas at higher concentrations glutathionylation remained at basal levels. Although oxidation with diamide increased glutathionylation, reactive oxygen species (ROS) were not involved in the Cd{sup 2+}-dependent effect, as only Cd{sup 2+} concentrations above 2 μM were sufficient to increase ROS. However, low [Cd{sup 2+}] increased total glutathione levels without affecting the ratio of reduced/oxidized glutathione, and inhibition of glutathione synthesis suppressed actin glutathionylation. Cadmium increased the activity of the enzyme glutaredoxin, which influences the equilibrium between glutathionylated and deglutathionylated proteins and thus may influence levels of glutathionylated actin. Together these observations show that cadmium-dependent effects on actin glutathionylation are affected by glutathione metabolism and not by direct effects of ROS on thiol chemistry. In vitro polymerization assays with glutathionylated actin show a decreased rate of polymerization. In contrast, immunofluorescence of cytoskeletal structure in intact cells suggests that increases in actin glutathionylation accompanying increased glutathione levels occurring under low Cd{sup 2+} exposure are protective in vivo, with cytoskeletal disruption ensuing only when higher Cd{sup 2+} concentrations increase ROS levels and prevent an increase in actin–glutathione conjugates. - Highlights: • Cadmium disrupts the actin cytoskeleton in mesangial cells. • Cadmium induces glutathionylation of actin at low concentrations. �

Cadmium-induced glutathionylation of actin occurs through a ROS-independent mechanism: Implications for cytoskeletal integrity

International Nuclear Information System (INIS)

Choong, Grace; Liu, Ying; Xiao, Weiqun; Templeton, Douglas M.

2013-01-01

Cadmium disrupts the actin cytoskeleton in rat mesangial cells, and we have previously shown that this involves a complex interplay involving activation of kinase signaling, protein translocation, and disruption of focal adhesions. Here we investigate the role that glutathionylation of actin plays in Cd 2+ -associated cytoskeletal reorganization. Low concentrations of Cd 2+ (0.5–2 μM) caused an increase in actin glutathionylation by 6 h, whereas at higher concentrations glutathionylation remained at basal levels. Although oxidation with diamide increased glutathionylation, reactive oxygen species (ROS) were not involved in the Cd 2+ -dependent effect, as only Cd 2+ concentrations above 2 μM were sufficient to increase ROS. However, low [Cd 2+ ] increased total glutathione levels without affecting the ratio of reduced/oxidized glutathione, and inhibition of glutathione synthesis suppressed actin glutathionylation. Cadmium increased the activity of the enzyme glutaredoxin, which influences the equilibrium between glutathionylated and deglutathionylated proteins and thus may influence levels of glutathionylated actin. Together these observations show that cadmium-dependent effects on actin glutathionylation are affected by glutathione metabolism and not by direct effects of ROS on thiol chemistry. In vitro polymerization assays with glutathionylated actin show a decreased rate of polymerization. In contrast, immunofluorescence of cytoskeletal structure in intact cells suggests that increases in actin glutathionylation accompanying increased glutathione levels occurring under low Cd 2+ exposure are protective in vivo, with cytoskeletal disruption ensuing only when higher Cd 2+ concentrations increase ROS levels and prevent an increase in actin–glutathione conjugates. - Highlights: • Cadmium disrupts the actin cytoskeleton in mesangial cells. • Cadmium induces glutathionylation of actin at low concentrations. • Glutathionylation requires glutathione

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

Science.gov (United States)

Egea, Javier; Fabregat, Isabel; Frapart, Yves M; Ghezzi, Pietro; Görlach, Agnes; Kietzmann, Thomas; Kubaichuk, Kateryna; Knaus, Ulla G; Lopez, Manuela G; Olaso-Gonzalez, Gloria; Petry, Andreas; Schulz, Rainer; Vina, Jose; Winyard, Paul; Abbas, Kahina; Ademowo, Opeyemi S; Afonso, Catarina B; Andreadou, Ioanna; Antelmann, Haike; Antunes, Fernando; Aslan, Mutay; Bachschmid, Markus M; Barbosa, Rui M; Belousov, Vsevolod; Berndt, Carsten; Bernlohr, David; Bertrán, Esther; Bindoli, Alberto; Bottari, Serge P; Brito, Paula M; Carrara, Guia; Casas, Ana I; Chatzi, Afroditi; Chondrogianni, Niki; Conrad, Marcus; Cooke, Marcus S; Costa, João G; Cuadrado, Antonio; My-Chan Dang, Pham; De Smet, Barbara; Debelec-Butuner, Bilge; Dias, Irundika H K; Dunn, Joe Dan; Edson, Amanda J; El Assar, Mariam; El-Benna, Jamel; Ferdinandy, Péter; Fernandes, Ana S; Fladmark, Kari E; Förstermann, Ulrich; Giniatullin, Rashid; Giricz, Zoltán; Görbe, Anikó; Griffiths, Helen; Hampl, Vaclav; Hanf, Alina; Herget, Jan; Hernansanz-Agustín, Pablo; Hillion, Melanie; Huang, Jingjing; Ilikay, Serap; Jansen-Dürr, Pidder; Jaquet, Vincent; Joles, Jaap A; Kalyanaraman, Balaraman; Kaminskyy, Danylo; Karbaschi, Mahsa; Kleanthous, Marina; Klotz, Lars-Oliver; Korac, Bato; Korkmaz, Kemal Sami; Koziel, Rafal; Kračun, Damir; Krause, Karl-Heinz; Křen, Vladimír; Krieg, Thomas; Laranjinha, João; Lazou, Antigone; Li, Huige; Martínez-Ruiz, Antonio; Matsui, Reiko; McBean, Gethin J; Meredith, Stuart P; Messens, Joris; Miguel, Verónica; Mikhed, Yuliya; Milisav, Irina; Milković, Lidija; Miranda-Vizuete, Antonio; Mojović, Miloš; Monsalve, María; Mouthuy, Pierre-Alexis; Mulvey, John; Münzel, Thomas; Muzykantov, Vladimir; Nguyen, Isabel T N; Oelze, Matthias; Oliveira, Nuno G; Palmeira, Carlos M; Papaevgeniou, Nikoletta; Pavićević, Aleksandra; Pedre, Brandán; Peyrot, Fabienne; Phylactides, Marios; Pircalabioru, Gratiela G; Pitt, Andrew R; Poulsen, Henrik E; Prieto, Ignacio; Rigobello, Maria Pia; Robledinos-Antón, Natalia; Rodríguez-Mañas, Leocadio; Rolo, Anabela P; Rousset, Francis; Ruskovska, Tatjana; Saraiva, Nuno; Sasson, Shlomo; Schröder, Katrin; Semen, Khrystyna; Seredenina, Tamara; Shakirzyanova, Anastasia; Smith, Geoffrey L; Soldati, Thierry; Sousa, Bebiana C; Spickett, Corinne M; Stancic, Ana; Stasia, Marie José; Steinbrenner, Holger; Stepanić, Višnja; Steven, Sebastian; Tokatlidis, Kostas; Tuncay, Erkan; Turan, Belma; Ursini, Fulvio; Vacek, Jan; Vajnerova, Olga; Valentová, Kateřina; Van Breusegem, Frank; Varisli, Lokman; Veal, Elizabeth A; Yalçın, A Suha; Yelisyeyeva, Olha; Žarković, Neven; Zatloukalová, Martina; Zielonka, Jacek; Touyz, Rhian M; Papapetropoulos, Andreas; Grune, Tilman; Lamas, Santiago; Schmidt, Harald H H W; Di Lisa, Fabio; Daiber, Andreas

2017-10-01

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Thymosin β10 expression driven by the human TERT promoter induces ovarian cancer-specific apoptosis through ROS production.

Directory of Open Access Journals (Sweden)

Young-Chae Kim

Full Text Available Thymosin β(10 (Tβ(10 regulates actin dynamics as a cytoplasm G-actin sequestering protein. Previously, we have shown that Tβ(10 diminishes tumor growth, angiogenesis, and proliferation by disrupting actin and by inhibiting Ras. However, little is known about its mechanism of action and biological function. In the present study, we establish a new gene therapy model using a genetically modified adenovirus, referred to as Ad.TERT.Tβ(10, that can overexpress the Tβ(10 gene in cancer cells. This was accomplished by replacing the native Tβ(10 gene promoter with the human TERT promoter in Ad.TERT.Tβ(10. We investigated the cancer suppression activity of Tβ(10 and found that Ad.TERT.Tβ(10 strikingly induced cancer-specific expression of Tβ(10 as well as apoptosis in a co-culture model of human primary ovarian cancer cells and normal fibroblasts. Additionally, Ad.TERT.Tβ(10 decreased mitochondrial membrane potential and increased reactive oxygen species (ROS production. These effects were amplified by co-treatment with anticancer drugs, such as paclitaxel and cisplatin. These findings indicate that the rise in ROS production due to actin disruption by Tβ(10 overexpression increases apoptosis of human ovarian cancer cells. Indeed, the cancer-specific overexpression of Tβ(10 by Ad.TERT.Tβ(10 could be a valuable anti-cancer therapeutic for the treatment of ovarian cancer without toxicity to normal cells.

An update on clinical oncology for the non-oncologist.

Science.gov (United States)

Kaliks, Rafael Aliosha

2016-01-01

ABSTRACTRecent advances in the understanding of tumor driver mutations, signaling pathways that lead to tumor progression, and the better understanding of the interaction between tumor cells and the immune system are revolutionizing cancer treatment. The pace at which new treatments are approved and the prices at which they are set have made it even more difficult to offer these treatments in countries like Brazil. In this review we present for the non-oncologist these new treatments and compare their availability in Brazilian public health system and private health system with that of developed countries.RESUMOAvanços recentes na compreensão de mutações promotoras de desenvolvimento do câncer, sinalização que leva à progressão de tumores, e o avanço no entendimento da interação entre as células tumorais e o sistema imunológico estão revolucionando o tratamento do câncer. A velocidade com que novos tratamentos são aprovados e o alto custo das medicações dificultam a disponibilização de terapêuticas em países como o Brasil. Nesta revisão, apresentamos ao não oncologista esses novos tratamentos e comparamos sua disponibilidade nos sistemas público e privado de saúde no Brasil com os países desenvolvidos.

Mechanism of Anti-glioblastoma Effect of Temzolomide Involved in ROS-Mediated SIRT 1 Pathway

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Yuan Jiang

2014-03-01

Full Text Available Objective: To explore the new molecular mechanism of anti-tumor effect of temzolomide (TMZon glioblastoma cell strain. Methods: MTT methods and Hoechst 33342 staining method were applied to determine the effect of TMZ on the proliferation and apoptosis of glioblastoma cell strains U251 and SHG44, while flow cytometry was used to detect the impact of TMZ on cellular cycles. Additionally, DCFH-DA probe was adopted to test intracellular reactive oxygen species (ROS level while Real-time PCR and Western blot tests were applied to determine the influence of TMZ on SIRT1 expression. Results: TMZ in different concentrations added into glioblastoma cell strain for 72 h could concentration-dependently inhibit the proliferation of glioblastoma cells, 100 μmol/L of which could also block cells in phase G2/M and improve cellular apoptosis. In addition, TMZ could evidently increase intracellular ROS level so as to activate SIRT1. Conclusion: The mechanism of anti-tumor effect of TMZ on glioblastoma may be associated with ROS-induced SIRT1 pathway, providing theoretical basis for the clinical efficacy of TMZ.

Low Interrater Reliability in Grading of Rectal Bleeding Using National Cancer Institute Common Toxicity Criteria and Radiation Therapy Oncology Group Toxicity Scales: A Survey of Radiation Oncologists

International Nuclear Information System (INIS)

Huynh-Le, Minh-Phuong; Zhang, Zhe; Tran, Phuoc T.; DeWeese, Theodore L.; Song, Daniel Y.

2014-01-01

Purpose: To measure concordance among genitourinary radiation oncologists in using the National Cancer Institute Common Toxicity Criteria (NCI CTC) and Radiation Therapy Oncology Group (RTOG) grading scales to grade rectal bleeding. Methods and Materials: From June 2013 to January 2014, a Web-based survey was sent to 250 American and Canadian academic radiation oncologists who treat prostate cancer. Participants were provided 4 case vignettes in which patients received radiation therapy and developed rectal bleeding and were asked for management plans and to rate the bleeding according to NCI CTC v.4 and RTOG late toxicity grading (scales provided). In 2 cases, participants were also asked whether they would send the patient for colonoscopy. A multilevel, random intercept modeling approach was used to assess sources of variation (case, respondent) in toxicity grading to calculate the intraclass correlation coefficient (ICC). Agreement on a dichotomous grading scale (low grades 1-2 vs high grades 3-4) was also assessed, using the κ statistic for multiple respondents. Results: Seventy-two radiation oncologists (28%) completed the survey. Forty-seven (65%) reported having either written or been principal investigator on a study using these scales. Agreement between respondents was moderate (ICC 0.52, 95% confidence interval [CI] 0.47-0.58) when using NCI CTC and fair using the RTOG scale (ICC 0.28, 95% CI 0.20-0.40). Respondents who chose an invasive management were more likely to select a higher toxicity grade (P<.0001). Using the dichotomous scale, we observed moderate agreement (κ = 0.42, 95% CI 0.40-0.44) with the NCI CTC scale, but only slight agreement with the RTOG scale (κ = 0.19, 95% CI 0.17-0.21). Conclusion: Low interrater reliability was observed among radiation oncologists grading rectal bleeding using 2 common scales. Clearer definitions of late rectal bleeding toxicity should be constructed to reduce this variability and avoid ambiguity in both

Organizacijos kultūros veiksnių įtaka AB "Pieno žvaigždės" darbuotojų motyvacijai

OpenAIRE

Gykaraitė, Reda

2010-01-01

Magistro baigiamajame darbe analizuojama Lietuvos ir užsienio autorių teoriniai teiginiai organizacijos kultūros ir darbuotojų motyvavimo klausimais, išryškinamos pagrindinės privataus sektoriaus darbuotojų motyvavimo priemonės, nagrinėjami pagrindiniai organizacijos kultūros veiksniai ir organizacijos kultūros pokyčiai. Tyrime dalyvavo 134 respondentai dirbantys įmonės AB „Pieno žvaigždės“ filiale „Mažeikių pieninė“. Remiantis anketinės apklausos rezultatais buvo identifikuota, kad daugiausi...

Strategies for the Management of Localized Prostate Cancer: A Guide for Radiation Oncologists

Energy Technology Data Exchange (ETDEWEB)

NONE

2014-09-15

Prostate cancer is a serious health issue, especially considering the recent epidemiological trend and its corresponding socioeconomic impact. Challenges encountered by treating physicians include the long natural history of the disease, the fact that it is more prevalent in the elderly and the difficulty in performing a complete critical review of medical evidence due to the plethora of available information. In addition, the difficulty in deciding if and when therapeutic intervention should be initiated is an important issue pertaining to this type of malignancy. However, there is one area where there is a uniform consensus: the applicability of the multidisciplinary approach in the management of prostate cancer. Clinical guidelines are systematically developed statements designed to help practitioners, managers and patients make decisions about appropriate health care for specific circumstances. Clinicians need simple, patient specific, user friendly guidelines. The main purposes of clinical guidelines are to: (a) provide recommendations for the treatment of individual patients by practitioners; (b) help develop standards to assess the individual practice of health professionals; (c) be used in the education and training of health professionals; (d) assist patients in making informed decisions; and (e) improve communication between patients and health professionals. Clinical guidelines for the management of prostate cancer exist in the published literature. However, these guidelines have usually been developed in and for affluent health care environments where all modern diagnostic and treatment modalities are available. In limited resource environments, the radiation oncologist is faced with the question of what the minimum acceptable (evidence based) line of action would be, considering the limited resources available. Clinical guidelines focusing on low to middle income countries aim to provide these practitioners with a practical tool. This publication is

Strategies for the Management of Localized Prostate Cancer: A Guide for Radiation Oncologists

International Nuclear Information System (INIS)

2014-01-01

Prostate cancer is a serious health issue, especially considering the recent epidemiological trend and its corresponding socioeconomic impact. Challenges encountered by treating physicians include the long natural history of the disease, the fact that it is more prevalent in the elderly and the difficulty in performing a complete critical review of medical evidence due to the plethora of available information. In addition, the difficulty in deciding if and when therapeutic intervention should be initiated is an important issue pertaining to this type of malignancy. However, there is one area where there is a uniform consensus: the applicability of the multidisciplinary approach in the management of prostate cancer. Clinical guidelines are systematically developed statements designed to help practitioners, managers and patients make decisions about appropriate health care for specific circumstances. Clinicians need simple, patient specific, user friendly guidelines. The main purposes of clinical guidelines are to: (a) provide recommendations for the treatment of individual patients by practitioners; (b) help develop standards to assess the individual practice of health professionals; (c) be used in the education and training of health professionals; (d) assist patients in making informed decisions; and (e) improve communication between patients and health professionals. Clinical guidelines for the management of prostate cancer exist in the published literature. However, these guidelines have usually been developed in and for affluent health care environments where all modern diagnostic and treatment modalities are available. In limited resource environments, the radiation oncologist is faced with the question of what the minimum acceptable (evidence based) line of action would be, considering the limited resources available. Clinical guidelines focusing on low to middle income countries aim to provide these practitioners with a practical tool. This publication is

Contemporary management of prostate cancer: a practice survey of Ontario genitourinary radiation oncologists

International Nuclear Information System (INIS)

Rodrigues, George; D'Souza, David; Crook, Juanita; Malone, Shawn; Sathya, Jinka; Morton, Gerard

2003-01-01

Objective: To survey radiation oncology practice in the utilization of hormonal and radiation therapy in the primary, adjuvant and salvage treatment of localized prostate cancer. Materials and methods: Genitourinary radiation oncologists practicing in Ontario were invited to participate in a practice survey examining staging, hormonal and radiation management, and radiation technique for a variety of common clinical scenarios. Background demographic information was collected on all respondents. The survey consisted of three cases relating to the hormonal/radiation management of low-, intermediate-, and high-risk prostate cancer as well as two adjuvant and one salvage post-prostatectomy scenarios. The survey response rate was 70% (26/37). Results: Clinicians were more likely to utilize laboratory and imaging studies for staging as the risk categorization increased. Low-risk disease was managed with radiation alone in 26/26 (70 Gy in 65%, 74-79.8 Gy in 35%). Intermediate-risk disease was managed with radiation (70 Gy in 46%, 74-79.8 Gy in 54%) with neoadjuvant hormones in 58%. All respondents managed high-risk disease with adjuvant hormones in addition to radiation therapy (70-71 Gy in 85%, and 76 Gy in 15%). In the pT3a, margin negative (PSA undetectable) scenario, most individuals would not recommend adjuvant radiation (73%). If margins were positive, 30% would still not recommend adjuvant radiation. In the salvage scenario (slowly rising PSA 4 years post-prostatectomy for pT2a close margin disease), all respondents would manage with radiation therapy. Hormones were not routinely recommended in the initial management of the adjuvant and salvage scenarios. Radiation doses utilized for both adjuvant and salvage treatment ranged from 60-70 Gy (median 66 Gy). Conclusions: General agreement exists for the management of low- and high-risk disease and in the post-prostatectomy salvage setting. Use of dose-escalation and neoadjuvant hormones in the intermediate

Ethanol stimulates ROS generation by mitochondria through Ca2+ mobilization and increases GFAP content in rat hippocampal astrocytes.

Science.gov (United States)

González, Antonio; Pariente, José A; Salido, Ginés M

2007-10-31

We have employed rat hippocampal astrocytes in culture to investigate the effect of ethanol on reactive oxygen species (ROS) production as well as its effect on [Ca2+]c and GFAP expression. Cells were loaded with the fluorescent probes fura-2 and H2DCFDA for the determination of changes in [Ca2+]c and ROS production respectively, employing spectrofluorimetry. GFAP content was determined by immunocytochemistry and confocal scanning microscopy. Our results show ROS production in response to 50 mM ethanol, that was reduced in Ca2+-free medium (containing 0.5 mM EGTA) and in the presence of the intracellular Ca2+ chelator BAPTA (10 microM). The effect of ethanol on ROS production was significantly reduced in the presence of the alcohol dehydrogenase inhibitor 4-methylpyrazole (1 mM), and the antioxidants resveratrol (100 microM) or catalase (300 U/ml). Preincubation of astrocytes in the presence of 10 microM antimycin plus 10 microM oligomycin to inhibit mitochondria completely blocked ethanol-evoked ROS production. In addition, ethanol led to a sustained increase in [Ca2+]c that reached a constant level over the prestimulation values. Finally, incubation of astrocytes in the presence of ethanol increased the content of GFAP that was significantly reduced in the absence of extracellular Ca2+ and by resveratrol and catalase pretreatment. The data obtained in the present study suggest that astrocytes are able to metabolize ethanol, which induces two effects on intracellular homeostasis: an immediate response (Ca2+ release and ROS generation) and later changes involving GFAP expression. Both effects may underline various signaling pathways which are important for cell proliferation, differentiation and function.

From hunting-based to nomadic reindeer herding in Røros and surrounding areas (In Norwegian with Summary in English

Directory of Open Access Journals (Sweden)

Sverre Fjellheim

2005-04-01

Full Text Available Until today most researchers have named central Sweden and the Arjeplog area as the cradle of reindeer nomadism. However, there are reasons to believe that the practice of nomadic reindeer herding goes at least as far back in Røros and surrounding areas. The transition was probably initiated by large-scale climatic changes during the 16th and 17th century. Local historian, Anders Reitan, characterises the end of the 16th and the beginning of the 17th century as very difficult for the Røros district, with cold weather and crop failure. He refers to the year 1591 as the "black year", when "the grass didn't turn green north of Dovre", and in 1599 there was "general crop failure throughout northern Europe". 1635 was ostensibly as bad as the "black year", and it was told that in 1647 several people died right next to the trees they had stripped for bark to eat. The cold climate is confirmed by today's climate researchers. In the sources the period from 1550 to 1850 is referred to as "the little ice-age". For the Trøndelag area this meant regular north-westerly and north-easterly winds during the spring, causing later snow-melting and more frequent snowfall and periods of frost than we have today. Summers were shorter and colder, and there was less sun and more rain than in our days. Under such circum¬stances there must have been a good market for meat, which must have put considerable pressure on the wild reindeer stock. However, the cold climate with shortage of food and famine during the 16th and 17th century did not only lead to an increase in the hunting of wild reindeer, but it must also have had a direct influence on the wild reindeer population. Researchers have found that the spring in particular was getting colder during the "little ice-age". And spring weather is of crucial importance to the dynamics of population and the procreative powers of wild reindeer. According to Julie Axman the weather was bad and conditions for the reindeer

Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

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Sada, Kiminori; Nishikawa, Takeshi; Kukidome, Daisuke; Yoshinaga, Tomoaki; Kajihara, Nobuhiro; Sonoda, Kazuhiro; Senokuchi, Takafumi; Motoshima, Hiroyuki; Matsumura, Takeshi; Araki, Eiichi

2016-01-01

We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

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Kiminori Sada

Full Text Available We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs, cellular hypoxia increased after incubation with high glucose (HG. A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1, a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

Global inhibition of reactive oxygen species (ROS inhibits paclitaxel-induced painful peripheral neuropathy.

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Mehmet Fidanboylu

Full Text Available Paclitaxel (Taxol® is a widely used chemotherapeutic agent that has a major dose limiting side-effect of painful peripheral neuropathy. Currently there is no effective therapy for the prevention or treatment of chemotherapy-induced painful peripheral neuropathies. Evidence for mitochondrial dysfunction during paclitaxel-induced pain was previously indicated with the presence of swollen and vacuolated neuronal mitochondria. As mitochondria are a major source of reactive oxygen species (ROS, the aim of this study was to examine whether pharmacological inhibition of ROS could reverse established paclitaxel-induced pain or prevent the development of paclitaxel-induced pain. Using a rat model of paclitaxel-induced pain (intraperitoneal 2 mg/kg paclitaxel on days 0, 2, 4 & 6, the effects of a non-specific ROS scavenger, N-tert-Butyl-α-phenylnitrone (PBN and a superoxide selective scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL were compared. Systemic 100 mg/kg PBN administration markedly inhibited established paclitaxel-induced mechanical hypersensitivity to von Frey 8 g and 15 g stimulation and cold hypersensitivity to plantar acetone application. Daily systemic administration of 50 mg/kg PBN (days -1 to 13 completely prevented mechanical hypersensitivity to von Frey 4 g and 8 g stimulation and significantly attenuated mechanical hypersensitivity to von Frey 15 g. Systemic 100 mg/kg TEMPOL had no effect on established paclitaxel-induced mechanical or cold hypersensitivity. High dose (250 mg/kg systemic TEMPOL significantly inhibited mechanical hypersensitivity to von Frey 8 g & 15 g, but to a lesser extent than PBN. Daily systemic administration of 100 mg/kg TEMPOL (day -1 to 12 did not affect the development of paclitaxel-induced mechanical hypersensitivity. These data suggest that ROS play a causal role in the development and maintenance of paclitaxel-induced pain, but such effects cannot be attributed to superoxide radicals

NADPH oxidase-2 derived ROS dictates murine DC cytokine-mediated cell fate decisions during CD4 T helper-cell commitment.

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Meghan A Jendrysik

Full Text Available NADPH oxidase-2 (Nox2/gp91(phox and p47(phox deficient mice are prone to hyper-inflammatory responses suggesting a paradoxical role for Nox2-derived reactive oxygen species (ROS as anti-inflammatory mediators. The molecular basis for this mode of control remains unclear. Here we demonstrate that IFNγ/LPS matured p47(phox-/--ROS deficient mouse dendritic cells (DC secrete more IL-12p70 than similarly treated wild type DC, and in an in vitro co-culture model IFNγ/LPS matured p47(phox-/- DC bias more ovalbumin-specific CD4(+ T lymphocytes toward a Th1 phenotype than wild type (WT DC through a ROS-dependent mechanism linking IL-12p70 expression to regulation of p38-MAPK activation. The Nox2-dependent ROS production in DC negatively regulates proinflammatory IL-12 expression in DC by constraining p38-MAPK activity. Increasing endogenous H(2O(2 attenuates p38-MAPK activity in IFNγ/LPS stimulated WT and p47(phox-/- DC, which suggests that endogenous Nox 2-derived ROS functions as a secondary messenger in the activated p38-MAPK signaling pathway during IL-12 expression. These findings indicate that ROS, generated endogenously by innate and adaptive immune cells, can function as important secondary messengers that can regulate cytokine production and immune cell cross-talk to control during the inflammatory response.

Involvement of CAT in the detoxification of HT-induced ROS burst in rice anther and its relation to pollen fertility.

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Zhao, Qian; Zhou, Lujian; Liu, Jianchao; Cao, Zhenzhen; Du, Xiaoxia; Huang, Fudeng; Pan, Gang; Cheng, Fangmin

2018-05-01

HT-induced ROS burst in developing anther is closely related to the lowered CAT activity as the result of the markedly suppressed OsCATB transcript, thereby causing severe fertility injury for rice plants exposed to HT at meiosis stage. The reproductive stage of rice plants is highly sensitive to heat stress. In this paper, different rice cultivars were used to investigate the relationship of HT-induced floret sterility with reactive oxygen species (ROS) detoxification in rice anthers under well-controlled climatic conditions. Results showed that high temperature (HT) exposure significantly enhanced the ROS level and malondialdehyde (MDA) content in developing anther, and the increase in ROS amount in rice anther under HT exposure was closely associated with HT-induced decline in the activities of several antioxidant enzymes. For various antioxidant enzymes, SOD and CAT were more susceptible to the ROS burst in rice anther induced by HT exposure than APX and POD, in which SOD and CAT activity in developing anther decreased significantly by HT exposure, whereas APX activity was relatively stable among different temperature regimes. HT-induced decrease in CAT activity was attributable to the suppressed transcript of OsCATB. This occurrence was strongly responsible for HT-induced increase in ROS level and oxidative-damage in rice anther, thereby it finally caused significant reduction in pollen viability and floret fertility for the rice plants exposed to HT during meiosis. Exogenous application of 1000 µM salicylic acid (SA) may alleviate HT-induced reduction in pollen viability and floret fertility, concomitantly with the increased CAT activity and reduced ROS level in rice anther.

Caenorhabditis elegans as a model for understanding ROS function in physiology and disease

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Antonio Miranda-Vizuete

2017-04-01

Full Text Available ROS (reactive oxygen species are potentially damaging by-products of aerobic metabolism which, unchecked, can have detrimental effects on cell function. However, it is now widely accepted that, at physiological levels, certain ROS play important roles in cell signaling, acting as second messengers to regulate cell choices that contribute to the development, adaptation and survival of plants and animals. Despite important recent advances in the biochemical tools available to study redox-signaling, the molecular mechanisms underlying most of these responses remain poorly understood, particularly in multicellular organisms. As we will review here, C. elegans has emerged as a powerful animal model to elucidate these and other aspects of redox biology.

Singlet oxygen and ROS in a new light: low-dose subcellular photodynamic treatment enhances proliferation at the single cell level.

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Blázquez-Castro, Alfonso; Breitenbach, Thomas; Ogilby, Peter R

2014-09-01

Two-photon excitation of a sensitizer with a focused laser beam was used to create a spatially-localized subcellular population of reactive oxygen species, ROS, in single HeLa cells. The sensitizer used was protoporphyrin IX, PpIX, endogenously derived from 5-aminolevulinic acid delivered to the cells. Although we infer that singlet oxygen, O2(a(1)Δg), is one ROS produced upon irradiation of PpIX under these conditions, it is possible that the superoxide ion, O2(-˙), may also play a role in this system. With a "high" dose of PpIX-sensitized ROS, the expected death of the cell was observed. However, under "low dose" conditions, clear signs of cell proliferation were observed. The present results facilitate studies of ROS-mediated signalling in imaging-based single cell experiments.

A natural antioxidant, tannic acid mitigates iron-overload induced hepatotoxicity in Swiss albino mice through ROS regulation.

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Basu, Tapasree; Panja, Sourav; Shendge, Anil Khushalrao; Das, Abhishek; Mandal, Nripendranath

2018-05-01

Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron-overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron-overload triggered hepatotoxicity, followed by oral administration of TA for remediation. After treatment, liver, spleen, and blood samples were processed from sacrificed animals. The liver iron, serum ferritin, serum markers, ROS, liver antioxidant status, and liver damage parameters were assessed, followed by histopathology and protein expression studies. Our results show that TA is a prominent ROS and RNS scavenger as well as iron chelator in vitro. It also reversed the ROS levels in vivo and restricted the liver damage parameters as compared to the standard drug, desirox. Moreover, this natural polyphenol exclusively ameliorates the histopathological and fibrotic changes in liver sections reducing the iron-overload, along with chelation of liver iron and normalization of serum ferritin. The protective role of TA against iron-overload induced apoptosis in liver was further supported by changed levels of caspase 3, PARP as well as Bax/BCl-2 ratio. Thus, TA can be envisaged as a better orally administrable iron chelator to reduce iron-overload induced hepatotoxicity through ROS regulation. © 2018 Wiley Periodicals, Inc.

Peroxisomal Polyamine Oxidase and NADPH-Oxidase cross-talk for ROS homeostasis which affects respiration rate in Arabidopsis thaliana

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Efthimios A. Andronis

2014-04-01

Full Text Available Homeostasis of reactive oxygen species (ROS in the intracellular compartments is of critical importance as ROS have been linked with nearly all cellular processes and more importantly with diseases and aging. PAs are nitrogenous molecules with an evolutionary conserved role in the regulation of metabolic and energetic status of cells. Recent evidence also suggests that polyamines (PA are major regulators of ROS homeostasis. In Arabidopsis the backconversion of the PAs spermidine (Spd and spermine (Spm to putrescine (Put and Spd, respectively is catalyzed by two peroxisomal PA oxidases (AtPAO. However, the physiological role of this pathway remains largely elusive. Here we explore the role of peroxisomal PA backconversion and in particular that catalyzed by the highly expressed AtPAO3 in the regulation of ROS homeostasis and mitochondrial respiratory burst. Exogenous PAs exert an NADPH-oxidase dependent stimulation of oxygen consumption, with Spd exerting the strongest effect. This increase is attenuated by treatment with the NADPH-oxidase blocker diphenyleneiodonium iodide (DPI. Loss-of-function of AtPAO3 gene results to increased NADPH-oxidase-dependent production of superoxide anions (O2.-, but not H2O2, which activate the mitochondrial alternative oxidase pathway (AOX. On the contrary, overexpression of AtPAO3 results to an increased but balanced production of both H2O2 and O2.-. These results suggest that the ratio of O2.-/H2O2 regulates respiratory chain in mitochondria, with PA-dependent production of O2.- by NADPH-oxidase tilting the balance of electron transfer chain in favor of the AOX pathway. In addition, AtPAO3 seems to be an important component in the regulating module of ROS homeostasis, while a conserved role for PA backconversion and ROS across kingdoms is discussed.

Extract from Edible Red Seaweed (Gelidium amansii) Inhibits Lipid Accumulation and ROS Production during Differentiation in 3T3-L1 Cells.

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Seo, Min-Jung; Lee, Ok-Hwan; Choi, Hyeon-Son; Lee, Boo-Yong

2012-06-01

Gelidium (G.) amansii is a red alga widely distributed in the shallow waters around East Asian countries. We investigated the effect of G. amansii on lipid accumulation and ROS (Reactive Oxygen Species) production in 3T3-L1 cells. G. amansii extracts dose-dependently inhibited lipid formation and ROS generation in cultured cells. Our results showed that anti-adipogenic effect of G. amansii was due to the reduction in mRNA expressions of PPARγ peroxisome proliferator-activated receptor-γ and aP2 (adipocyte protein 2). G. amansii extracts significantly decreased mRNA levels of a ROS-generator, NOX4 (nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4), and increased the protein levels of antioxidant enzymes including SOD1/2 (superoxide dis-mutases), Gpx (glutathione peroxidase), and GR (glutathione reductase), which can lead to the reduction of ROS in the cell. In addition, the G. amansii extract enhanced mRNA levels of adiponectin, one of the adipokines secreted from adipocytes, and GLUT4, glucose uptake protein. Taken together, our study shows that G. amansii extract inhibited lipid accumulation and ROS production by controlling adipogenic signals and ROS regulating genes.

Vaikas – reklamos auka ar vartotojiškos kultūros produktas: teorinio diskurso konceptualizavimas

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Ponelienė, Reda

2011-01-01

Straipsnyje teoriniu lygmeniu grindžiamas šiandienos visuomenėje egzistuojantis vaiko vartotojo (arba vartotojiškos kultūros produkto) ir vaiko kaip reklamos aukos (arba to, kurį vartoja) diskursas. Remiantis Lietuvos ir užsienio mokslininkų atliktų tyrimų rezultatais, aptariami įvairūs nagrinėjamos problemos aspektai: vieni autoriai dėmesį skiria vaiko ir reklamos santykiui, kiti – vaikų vartojimo kultūros sudėtingumui aptarti, treti – metodų, kaip susilpninti į vaikus, kaip nesąmoningus var...

ROS-dependent anticandidal activity of zinc oxide nanoparticles synthesized by using egg albumen as a biotemplate

International Nuclear Information System (INIS)

Shoeb, M; Singh, Braj R; Khan, Javed A; Khan, Wasi; Naqvi, Alim H; Singh, Brahma N; Singh, Harikesh B

2013-01-01

Zinc oxide nanoparticles (ZnO NPs) have attracted great attention because of their superior optical properties and wide application in biomedical science. However, little is known about the anticandidal activity of ZnO NPs against Candida albicans (C. albicans). This study was designed to develop the green approach to synthesize ZnO NPs using egg white (denoted as EtZnO NPs) and investigated its possible mechanism of antimicrobial activity against C. albicans 077. It was also notable that anticandidal activity of EtZnO NPs is correlated with reactive oxygen species (ROS) production in a dose dependent manner. Protection of histidine against ROS clearly suggests the implication of ROS in anticandidal activity of EtZnO NPs. This green approach based on egg white-mediated synthesis of ZnO NPs paves the way for developing cost effective, eco-friendly and promising antimicrobial nanomaterial for applications in medicine. (paper)

Observer variation in target volume delineation of lung cancer related to radiation oncologist-computer interaction: A 'Big Brother' evaluation

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Steenbakkers, Roel J.H.M.; Duppen, Joop C.; Fitton, Isabelle; Deurloo, Kirsten E.I.; Zijp, Lambert; Uitterhoeve, Apollonia L.J.; Rodrigus, Patrick T.R.; Kramer, Gijsbert W.P.; Bussink, Johan; Jaeger, Katrien De; Belderbos, Jose S.A.; Hart, Augustinus A.M.; Nowak, Peter J.C.M.; Herk, Marcel van; Rasch, Coen R.N.

2005-01-01

Background and purpose: To evaluate the process of target volume delineation in lung cancer for optimization of imaging, delineation protocol and delineation software. Patients and methods: Eleven radiation oncologists (observers) from five different institutions delineated the Gross Tumor Volume (GTV) including positive lymph nodes of 22 lung cancer patients (stages I-IIIB) on CT only. All radiation oncologist-computer interactions were recorded with a tool called 'Big Brother'. For each radiation oncologist and patient the following issues were analyzed: delineation time, number of delineated points and corrections, zoom levels, level and window (L/W) settings, CT slice changes, use of side windows (coronal and sagittal) and software button use. Results: The mean delineation time per GTV was 16 min (SD 10 min). The mean delineation time for lymph node positive patients was on average 3 min larger (P=0.02) than for lymph node negative patients. Many corrections (55%) were due to L/W change (e.g. delineating in mediastinum L/W and then correcting in lung L/W). For the lymph node region, a relatively large number of corrections was found (3.7 corr/cm 2 ), indicating that it was difficult to delineate lymph nodes. For the tumor-atelectasis region, a relative small number of corrections was found (1.0 corr/cm 2 ), indicating that including or excluding atelectasis into the GTV was a clinical decision. Inappropriate use of L/W settings was frequently found (e.g. 46% of all delineated points in the tumor-lung region were delineated in mediastinum L/W settings). Despite a large observer variation in cranial and caudal direction of 0.72 cm (1 SD), the coronal and sagittal side windows were not used in 45 and 60% of the cases, respectively. For the more difficult cases, observer variation was smaller when the coronal and sagittal side windows were used. Conclusions: With the 'Big Brother' tool a method was developed to trace the delineation process. The differences between

Comparison of detection methods and follow-up study on the tyrosine kinase inhibitors therapy in non-small cell lung cancer patients with ROS1 fusion rearrangement

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Wu, Jieyu; Lin, Yunen; He, Xinming; Yang, Haihong; He, Ping; Fu, Xinge; Li, Guangqiu; Gu, Xia

2016-01-01

The screening of ROS proto-oncogene 1, receptor tyrosine kinase(ROS1) fusion rearrangement might be potentially beneficial for an effective therapy against non-small cell lung cancer (NSCLC). However, the three main ROS1 rearrangement detection methods have limitations, and no routine protocol for the detection of ROS1 rearrangement in NSCLC is available. In this study, our aims were to compare immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qRT-PCR) in their ability to detect ROS1 rearrangement in NSCLC, and discuss the clinical characteristics and histopathology of the patients with ROS1 rearrangement. Moreover, the effects of tyrosine kinase inhibitors (TKIs) therapy on the patients with ROS1 rearrangement and advanced stage disease (III b–IV) were investigated. Patients with a previously diagnosed NSCLC were recruited in this study from November 2013 to October 2015. IHC was performed using the D4D6 monoclonal antibody (mAb) in an automatic IHC instrument, while FISH and qRT-PCR were carried out to confirm the IHC results. FISH and qRT-PCR positive cases underwent direct sequencing. After detection, patients with advanced ROS1 rearranged NSCLC had received TKI therapy. Two hundred and thirty-eight patients were included in this study. ROS1 rearrangement was detected in 10 patients. The concordant rate of FISH and qRT-PCR results was 100 %, while in the FISH and IHC results high congruence was present when IHC showed a diffusely (≥60 % tumor cells) 2–3+ cytoplasmic reactivity pattern. Patients harboring ROS1 rearrangement were mostly young (8/10), females (7/10) and non-smokers (7/10) with adenocarcinoma (10/10) and acinar pattern. Most of their tumor were in intermediate grade (6/8). Among these 10 patients, three of them in stage IV with ROS1 rearrangement gained benefits from ROS1 TKI therapy. IHC, FISH and qRT-PCR can reliably detect ROS1 rearrangement in NSCLC, while IHC can be

Fusobacterium nucleatum-Induced Impairment of Autophagic Flux Enhances the Expression of Proinflammatory Cytokines via ROS in Caco-2 Cells.

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Bin Tang

Full Text Available Fusobacterium nucleatum (F. nucleatum plays a critical role in gastrointestinal inflammation. However, the exact mechanism by which F. nucleatum contributes to inflammation is unclear. In the present study, it was revealed that F. nucleatum could induce the production of proinflammatory cytokines (IL-8, IL-1β and TNF-α and reactive oxygen species (ROS in Caco-2 colorectal adenocarcinoma cells. Furthermore, ROS scavengers (NAC or Tiron could decrease the production of proinflammatory cytokines during F. nucleatum infection. In addition, we observed that autophagy is impaired in Caco-2 cells after F. nucleatum infection. The production of proinflammatory cytokines and ROS induced by F. nucleatum was enhanced with either autophagy pharmacologic inhibitors (3-methyladenine, bafilomycin A1 or RNA interference in essential autophagy genes (ATG5 or ATG12 in Caco-2 cells. Taken together, these results indicate that F. nucleatum-induced impairment of autophagic flux enhances the expression of proinflammatory cytokines via ROS in Caco-2 Cells.

Perceptions of Oncologists, Healthcare Policy Makers, Patients and the General Population on the Value of Pharmaceutical Treatments in Oncology.

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Sacristán, José A; Lizan, Luís; Comellas, Marta; Garrido, Pilar; Avendaño, Cristina; Cruz-Hernández, Juan J; Espinosa, Javier; Dilla, Tatiana

2016-11-01

The purpose of this study was to explore the main factors explaining the relative weight of the different attributes that determine the value of oncologic treatments from the different perspectives of healthcare policy makers (HCPM), oncologists, patients and the general population in Spain. Structured interviews were conducted to assess: (1) the importance of the attributes on treatment choice when comparing a new cancer drug with a standard cancer treatment; (2) the importance of survival, quality of life (QoL), costs and innovation in cancer; and (3) the most worrying side effects related to cancer drugs. A total of 188 individuals participated in the study. For all participants, when choosing treatments, the best rated characteristics were greater efficacy, greater safety, treatment adaptation to patients' individual requirements and the rapid reincorporation of patients to their daily activities. There were important differences among participants in their opinion about survival, QoL and cost. In general, oncologists, patients, and the general population gave greater value to gains in QoL than healthcare policy makers. Compared to other participants healthcare policy makers gave greater importance to the economic impact related to oncology treatments. Gains in QoL, survival, safety, cost and innovation are perceived differently by different groups of stakeholders. It is recommended to consider the perspective of different stakeholders in the assessment of a new cancer drugs to obtain more informed decisions when deciding on the most appropriate treatment to use. Eli Lilly & Co, Madrid (Spain).

TMEPAI regulates EMT in lung cancer cells by modulating the ROS and IRS-1 signaling pathways.

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Hu, Ying; He, Kai; Wang, Dongmei; Yuan, Xinwang; Liu, Yi; Ji, Hongbin; Song, Jianguo

2013-08-01

The epithelial-mesenchymal transition (EMT) has been implicated in various pathophysiological processes, including cancer cell migration and distal metastasis. Reactive oxygen species (ROS) and insulin receptor substrate-1 (IRS-1) are important in cancer progression and regulation of EMT. To explore the biological significance and regulatory mechanism of EMT, we determined the expression, the biological function and the signaling pathway of prostate transmembrane protein, androgen induced-1 (TMEPAI), during the induction of EMT and cell migration. Transforming growth factor (TGF)-β1 significantly upregulated the expression of TMEPAI during EMT in human lung adenocarcinoma. Depletion of TMEPAI abolished TGF-β1-induced downregulation of ferritin heavy chain and the subsequent generation of ROS, thus suppressing TGF-β1-induced EMT and cell migration. In addition, increased ROS production and overexpression of TMEPAI downregulated the level of IRS-1. Both the addition of H2O2 and IRS-1 small interfering RNA rescued the ability of TGF-β1 to induce EMT in TMEPAI-depleted cells. Remarkably, the levels of TMEPAI in lung tumor tissues are very high, whereas its expression in normal lung epithelium is very low. Moreover, TMEPAI expression was positively correlated with the cell mesenchymal phenotype and migration potential. Our work reveals that TMEPAI contributes to TGF-β1-induced EMT through ROS production and IRS-1 downregulation in lung cancer cells.

Overload training inhibits phagocytosis and ROS generation of peritoneal macrophages: role of IGF-1 and MGF.

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Xiao, Weihua; Chen, Peijie; Wang, Ru; Dong, Jingmei

2013-01-01

We tested the hypothesis that overload training inhibits the phagocytosis and the reactive oxygen species (ROS) generation of peritoneal macrophages (Mϕs), and that insulin-like growth factor-1(IGF-1) and mechano-growth factor (MGF) produced by macrophages may contribute to this process. Rats were randomized to two groups, sedentary control group (n = 10) and overload training group (n = 10). The rats of overload training group were subjected to 11 weeks of experimental training protocol. Blood sample was used to determine the content of hemoglobin, testosterone, and corticosterone. The phagocytosis and the ROS generation of Mϕs were measured by the uptake of neutral red and the flow cytometry, respectively. IGF-1 and MGF mRNA levels in Mϕs were determined by real-time PCR. In addition, we evaluated the effects of IGF-1 and MGF peptide on phagocytosis and ROS generation of Mϕs in vitro. The data showed that overload training significantly decreased the body weight (19.3 %, P overload training significantly decreased the phagocytosis (27 %, P overload training group increased significantly compared with the control group (21-fold and 92-fold, respectively; P overload training inhibits the phagocytosis and the ROS generation of peritoneal macrophages, and that MGF produced by macrophages may play a key role in this process. This may represent a novel mechanism of immune suppression induced by overload training.

Non-thermal plasma induces mitochondria-mediated apoptotic signaling pathway via ROS generation in HeLa cells.

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Li, Wei; Yu, K N; Ma, Jie; Shen, Jie; Cheng, Cheng; Zhou, Fangjian; Cai, Zhiming; Han, Wei

2017-11-01

Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. Although increasing evidence suggests that NTP selectively induces apoptosis in some types of tumor cells, the molecular mechanisms underlying this phenomenon remain unclear. In this study, we further investigated possible molecular mechanisms for NTP-induced apoptosis of HeLa cells. The results showed that NTP exposure significantly inhibited the growth and viability of HeLa cells. Morphological observation and flow cytometry analysis demonstrated that NTP exposure induced HeLa cell apoptosis. NTP exposure also activated caspase-9 and caspase-3, which subsequently cleaved poly (ADP- ribose) polymerase. Furthermore, NTP exposure suppressed Bcl-2 expression, enhanced Bax expression and translocation to mitochondria, activated mitochondria-mediated apoptotic pathway, followed by the release of cytochrome c. Further studies showed that NTP treatment led to ROS generation, whereas blockade of ROS generation by N-acetyl-l-cysteine (NAC, ROS scavengers) significantly prevented NTP-induced mitochondrial alteration and subsequent apoptosis of HeLa cells via suppressing Bax translocation, cytochrome c and caspase-3 activation. Taken together, our results indicated that NTP exposure induced mitochondria-mediated intrinsic apoptosis of HeLa cells was activated by ROS generation. These findings provide insights to the therapeutic potential and clinical research of NTP as a novel tool in cervical cancer treatment. Copyright © 2017. Published by Elsevier Inc.

PERK pathway is involved in oxygen-glucose-serum deprivation-induced NF-kB activation via ROS generation in spinal cord astrocytes.

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Liu, Jinbo; Du, Lijian

2015-11-13

Mitochondrial dysfunction is a direct target of hypoxic/ischemic stress in astrocytes, which results in the increased production of reactive oxygen species (ROS). Previous reports showed that ROS can activate NF-kB in spinal cord astrocytes, which occurs as a secondary injury during the pathological process of spinal cord injury (SCI). Protein kinase RNA (PKR)-like ER kinase (PERK) plays an important role in mitochondrial dysfunction. To elucidate the specific role of PERK in hypoxic/ischemic-induced NF-kB activation in spinal astrocytes, we utilized an in vitro oxygen-glucose deprivation (OGD) model, which showed an enhanced formation of ROS and NF-kB activation. Knockdown of PERK resulted in reduced activation of PERK and ROS generation in astrocytes under OGD conditions. Notably, the knockdown of PERK also induced NF-kB activation in astrocytes. These data suggest that PERK is required for the hypoxic/ischemic-induced-dependent regulation of ROS and that it is involved in NF-kB activation in the astrocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

Autophagy Inhibition Contributes to ROS-Producing NLRP3-Dependent Inflammasome Activation and Cytokine Secretion in High Glucose-Induced Macrophages.

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Dai, Jiezhi; Zhang, Xiaotian; Li, Li; Chen, Hua; Chai, Yimin

2017-01-01

Type 2 diabetes is a persistent inflammatory response that impairs the healing process. We hypothesized that stimulation with high glucose following a pro-inflammatory signal would lead to autophagy inhibition, reactive oxygen species (ROS) production and eventually to the activation of the Nod-like receptor protein (NLRP) -3. Macrophages were isolated from human diabetic wound. We measured the expression of NLRP3, caspase1 and interleukin-1 beta (IL-1β) by western blot and real-time PCR, and the surface markers on cells by flow cytometry. THP-1-derived macrophages exposed to high glucose were applied to study the link between autophagy, ROS and NLRP3 activation. LC3-II, P62, NLRP3 inflammation and IL-1β expression were measured by western blot and real-time PCR. ROS production was measured with a Cellular Reactive Oxygen Species Detection Assay Kit. Macrophages isolated from diabetic wounds exhibited a pro-inflammatory phenotype, including sustained NLRP3 inflammasome activity associated with IL-1β secretion. Our data showed that high glucose inhibited autophagy, induced ROS production, and activated NLRP3 inflammasome and cytokine secretion in THP-1-derived macrophages. To study high glucose-induced NLRP3 inflammasome signalling, we performed studies using an autophagy inducer, a ROS inhibitor and a NLRP3 inhibitor and found that all reduced the NLRP3 inflammasome activation and cytokine secretion. Sustained NLRP3 inflammasome activity in wound-derived macrophages contributes to the hyper-inflammation in human diabetic wounds. Autophagy inhibition and ROS generation play an essential role in high glucose-induced NLRP3 inflammasome activation and cytokine secretion in macrophages. © 2017 The Author(s). Published by S. Karger AG, Basel.

The current and future role of the medical oncologist in the professional care for cancer patients: a position paper by the European Society for Medical Oncology (ESMO).

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Popescu, R A; Schäfer, R; Califano, R; Eckert, R; Coleman, R; Douillard, J-Y; Cervantes, A; Casali, P G; Sessa, C; Van Cutsem, E; de Vries, E; Pavlidis, N; Fumasoli, K; Wörmann, B; Samonigg, H; Cascinu, S; Cruz Hernández, J J; Howard, A J; Ciardiello, F; Stahel, R A; Piccart, M

2014-01-01

The number of cancer patients in Europe is rising and significant advances in basic and applied cancer research are making the provision of optimal care more challenging. The concept of cancer as a systemic, highly heterogeneous and complex disease has increased the awareness that quality cancer care should be provided by a multidisciplinary team (MDT) of highly qualified healthcare professionals. Cancer patients also have the right to benefit from medical progress by receiving optimal treatment from adequately trained and highly skilled medical professionals. Built on the highest standards of professional training and continuing medical education, medical oncology is recognised as an independent medical specialty in many European countries. Medical oncology is a core member of the MDT and offers cancer patients a comprehensive and systemic approach to treatment and care, while ensuring evidence-based, safe and cost-effective use of cancer drugs and preserving the quality of life of cancer patients through the entire 'cancer journey'. Medical oncologists are also engaged in clinical and translational research to promote innovation and new therapies and they contribute to cancer diagnosis, prevention and research, making a difference for patients in a dynamic, stimulating professional environment. Medical oncologists play an important role in shaping the future of healthcare through innovation and are also actively involved at the political level to ensure a maximum contribution of the profession to Society and to tackle future challenges. This position paper summarises the multifarious and vital contributions of medical oncology and medical oncologists to today's and tomorrow's professional cancer care.

Intracellular ROS mediates gas plasma-facilitated cellular transfection in 2D and 3D cultures

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Xu, Dehui; Wang, Biqing; Xu, Yujing; Chen, Zeyu; Cui, Qinjie; Yang, Yanjie; Chen, Hailan; Kong, Michael G.

2016-01-01

This study reports the potential of cold atmospheric plasma (CAP) as a versatile tool for delivering oligonucleotides into mammalian cells. Compared to lipofection and electroporation methods, plasma transfection showed a better uptake efficiency and less cell death in the transfection of oligonucleotides. We demonstrated that the level of extracellular aqueous reactive oxygen species (ROS) produced by gas plasma is correlated with the uptake efficiency and that this is achieved through an increase of intracellular ROS levels and the resulting increase in cell membrane permeability. This finding was supported by the use of ROS scavengers, which reduced CAP-based uptake efficiency. In addition, we found that cold atmospheric plasma could transfer oligonucleotides such as siRNA and miRNA into cells even in 3D cultures, thus suggesting the potential for unique applications of CAP beyond those provided by standard transfection techniques. Together, our results suggest that cold plasma might provide an efficient technique for the delivery of siRNA and miRNA in 2D and 3D culture models. PMID:27296089

Acetylcholine Attenuates Hypoxia/ Reoxygenation-Induced Mitochondrial and Cytosolic ROS Formation in H9c2 Cells via M2 Acetylcholine Receptor

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Yi Miao

2013-02-01

Full Text Available Background: The anti-infammatory and cardioprotective effect of acetylcholine (ACh has been reported; nevertheless, whether and how ACh exhibits an antioxidant property against ischemia/reperfusion (I/R-induced oxidative stress remains obscure. Methods: In the present study, H9c2 rat cardiomyocytes were exposed to hypoxia/reoxygenation (H/R to mimic I/R injury. We estimated intracellular different sources of reactive oxygen species (ROS by measuring mitochondrial ROS (mtROS, mitochondrial DNA (mtDNA copy number, xanthine oxidase (XO and NADPH oxidase (NOX activity and expression of rac 1. Cell injury was determined by lactate dehydrogenase (LDH release and cleaved caspase-3 expression. The siRNA transfection was performed to knockdown of M2 acetylcholine receptor (M2 AChR expression. Results: 12-h hypoxia followed by 2-h reoxygenation resulted in an abrupt burst of ROS in H9c2 cells. Administration of ACh reduced the levels of ROS in a concentration-dependent manner. Compared to the H/R group, ACh decreased mtROS, recovered mtDNA copy number, diminished XO and NOX activity, rac 1 expression as well as cell injury. Co- treatment with atropine rather than hexamethonium abolished the antioxidant and cardioprotective effect of ACh. Moreover, knockdown of M2 AChR by siRNA showed the similar trends as atropine co-treatment group. Conclusions: ACh inhibits mitochondria-, XO- and NOX-derived ROS production thus protecting H9c2 cells against H/R-induced oxidative stress, and these benefcial effects are mainly mediated by M2 AChR. Our findings suggested that increasing ACh release could be a potential therapeutic strategy for treatment and prevention of I/R injury.

ROS mediates interferon gamma induced phosphorylation of Src, through the Raf/ERK pathway, in MCF-7 human breast cancer cell line.

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Zibara, Kazem; Zeidan, Asad; Bjeije, Hassan; Kassem, Nouhad; Badran, Bassam; El-Zein, Nabil

2017-03-01

Interferon gamma (IFN-ɣ) is a pleiotropic cytokine which plays dual contrasting roles in cancer. Although IFN-ɣ has been clinically used to treat various malignancies, it was recently shown to have protumorigenic activities. Reactive oxygen species (ROS) are overproduced in cancer cells, mainly due to NADPH oxidase activity, which results into several changes in signaling pathways. In this study, we examined IFN-ɣ effect on the phosphorylation levels of key signaling proteins, through ROS production, in the human breast cancer cell line MCF-7. After treatment by IFN-ɣ, results showed a significant increase in the phosphorylation of STAT1, Src, raf, AKT, ERK1/2 and p38 signaling molecules, in a time specific manner. Src and Raf were found to be involved in early stages of IFN-ɣ signaling since their phosphorylation increased very rapidly. Selective inhibition of Src-family kinases resulted in an immediate significant decrease in the phosphorylation status of Raf and ERK1/2, but not p38 and AKT. On the other hand, IFN-ɣ resulted in ROS generation, through H 2 O 2 production, whereas pre-treatment with the ROS inhibitor NAC caused ROS inhibition and a significant decrease in the phosphorylation levels of AKT, ERK1/2, p38 and STAT1. Moreover, pretreatment with a selective NOX1 inhibitor resulted in a significant decrease of AKT phosphorylation. Finally, no direct relationship was found between ROS production and calcium mobilization. In summary, IFN-ɣ signaling in MCF-7 cell line is ROS-dependent and follows the Src/Raf/ERK pathway whereas its signaling through the AKT pathway is highly dependent on NOX1.

Mitogen-activated protein kinase kinase kinase (MAPKKK) 4 from rapeseed (Brassica napus L.) is a novel member inducing ROS accumulation and cell death

Energy Technology Data Exchange (ETDEWEB)

Li, Liang, E-mail: 18710470987@163.com; Ye, Chaofei, E-mail: yechaofei001@163.com; Zhao, Rui, E-mail: 571828628@qq.com; Li, Xin, E-mail: 1458272138@qq.com; Liu, Wu-zhen, E-mail: happywuzhenliu@163.com; Wu, Feifei, E-mail: 283915941@qq.com; Yan, Jingli, E-mail: yanjingli512@163.com; Jiang, Yuan-Qing, E-mail: jiangyq@nwafu.edu.cn; Yang, Bo, E-mail: yangwl@nwafu.edu.cn

2015-11-27

MAPKKK is the largest family of MAPK cascade, which is known to play important roles in plant growth, development and immune responses. So far, only a few have been functionally characterized even in the model plant, Arabidopsis due to the potential functional redundancy of MAPKKK. We previously identified and cloned a few MAPKKK family genes from rapeseed. In this study, BnaMAPKKK4 was characterized as a member in eliciting accumulation of reactive oxygen species (ROS) and hypersensitive response (HR)-like cell death. This is accompanied with accumulation of malondialdehyde (MDA), anthocyanin as well as nuclear DNA fragmentation. The transcript abundance of a series of ROS accumulation, cell death, and defense response related genes were up-regulated by the expression of MAPKKK4. Further investigation identified BnaMAPKKK4 elicited ROS through the downstream MPK3. These results indicate that BnaMAPKKK4 and its downstream components function in the ROS-induced cell death. - Highlights: • Expression of rapeseed MAPKKK4 induced ROS accumulation and cell death in leaves. • Cell death induced by MAPKKK4 is associated with membrane lipid peroxidation and DNA fragmentation. • MAPKKK4 interacts with MKK5 and MPK3. • MAPKKK4-induced ROS accumulation and cell death require downstream WIPK and SIPK. • MAPKKK4 is a novel MAPKKK modulating ROS accumulation and cell death.

Mitogen-activated protein kinase kinase kinase (MAPKKK) 4 from rapeseed (Brassica napus L.) is a novel member inducing ROS accumulation and cell death

International Nuclear Information System (INIS)

Li, Liang; Ye, Chaofei; Zhao, Rui; Li, Xin; Liu, Wu-zhen; Wu, Feifei; Yan, Jingli; Jiang, Yuan-Qing; Yang, Bo

2015-01-01

MAPKKK is the largest family of MAPK cascade, which is known to play important roles in plant growth, development and immune responses. So far, only a few have been functionally characterized even in the model plant, Arabidopsis due to the potential functional redundancy of MAPKKK. We previously identified and cloned a few MAPKKK family genes from rapeseed. In this study, BnaMAPKKK4 was characterized as a member in eliciting accumulation of reactive oxygen species (ROS) and hypersensitive response (HR)-like cell death. This is accompanied with accumulation of malondialdehyde (MDA), anthocyanin as well as nuclear DNA fragmentation. The transcript abundance of a series of ROS accumulation, cell death, and defense response related genes were up-regulated by the expression of MAPKKK4. Further investigation identified BnaMAPKKK4 elicited ROS through the downstream MPK3. These results indicate that BnaMAPKKK4 and its downstream components function in the ROS-induced cell death. - Highlights: • Expression of rapeseed MAPKKK4 induced ROS accumulation and cell death in leaves. • Cell death induced by MAPKKK4 is associated with membrane lipid peroxidation and DNA fragmentation. • MAPKKK4 interacts with MKK5 and MPK3. • MAPKKK4-induced ROS accumulation and cell death require downstream WIPK and SIPK. • MAPKKK4 is a novel MAPKKK modulating ROS accumulation and cell death.

Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.

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Liu, Zhong-wei; Wang, Jun-kui; Qiu, Chuan; Guan, Gong-chang; Liu, Xin-hong; Li, Shang-jian; Deng, Zheng-rong

2015-03-01

Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

The ROS/SUMO Axis Contributes to the Response of Acute Myeloid Leukemia Cells to Chemotherapeutic Drugs

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Guillaume Bossis

2014-06-01

Full Text Available Chemotherapeutic drugs used in the treatment of acute myeloid leukemias (AMLs are thought to induce cancer cell death through the generation of DNA double-strand breaks. Here, we report that one of their early effects is the loss of conjugation of the ubiquitin-like protein SUMO from its targets via reactive oxygen species (ROS-dependent inhibition of the SUMO-conjugating enzymes. Desumoylation regulates the expression of specific genes, such as the proapoptotic gene DDIT3, and helps induce apoptosis in chemosensitive AMLs. In contrast, chemotherapeutics do not activate the ROS/SUMO axis in chemoresistant cells. However, pro-oxidants or inhibition of the SUMO pathway by anacardic acid restores DDIT3 expression and apoptosis in chemoresistant cell lines and patient samples, including leukemic stem cells. Finally, inhibition of the SUMO pathway decreases tumor growth in mice xenografted with AML cells. Thus, targeting the ROS/SUMO axis might constitute a therapeutic strategy for AML patients resistant to conventional chemotherapies.

Enterococcus faecalis Infection Causes Inflammation, Intracellular Oxphos-Independent ROS Production, and DNA Damage in Human Gastric Cancer Cells

DEFF Research Database (Denmark)

Strickertsson, Jesper A. B; Desler, Claus; Martin-Bertelsen, Tomas

2013-01-01

therefore wanted to study the impact of E. faecalis infection on inflammatory response, reactive oxygen species (ROS) formation, mitochondrial respiration, and mitochondrial genetic stability in gastric mucosal cells. Methods To separate the changes induced by bacteria from those of the inflammatory cells...... intracellular ROS production through a pathway independent of oxidative phosphorylation (oxphos). Furthermore, E. faecalis infection induced mitochondrial DNA instability. Following infection, genes coding for inflammatory response proteins were transcriptionally up-regulated while DNA damage repair and cell...... cycle control genes were down-regulated. Cell growth slowed down when infected with viable E. faecalis and responded in a dose dependent manner to E. faecalis lysate. Conclusions Infection by E. faecalis induced an oxphos-independent intracellular ROS response and damaged the mitochondrial genome...

Emodin enhances the chemosensitivity of endometrial cancer by inhibiting ROS-mediated Cisplatin-resistance.

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Ding, Ning; Zhang, Hong; Su, Shan; Ding, Yumei; Yu, Xiaohui; Tang, Yujie; Wang, Qingfang; Liu, Peishu

2017-12-18

Background Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure. Objective Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied. Method CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting. Results Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drug-resistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin. Conclusion This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Silver Nanoparticles Induce HePG-2 Cells Apoptosis Through ROS-Mediated Signaling Pathways

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Zhu, Bing; Li, Yinghua; Lin, Zhengfang; Zhao, Mingqi; Xu, Tiantian; Wang, Changbing; Deng, Ning

2016-04-01

Recently, silver nanoparticles (AgNPs) have been shown to provide a novel approach to overcome tumors, especially those of hepatocarcinoma. However, the anticancer mechanism of silver nanoparticles is unclear. Thus, the purpose of this study was to estimate the effect of AgNPs on proliferation and activation of ROS-mediated signaling pathway on human hepatocellular carcinoma HePG-2 cells. A simple chemical method for preparing AgNPs with superior anticancer activity has been showed in this study. AgNPs were detected by transmission electronic microscopy (TEM) and energy dispersive X-ray (EDX). The size distribution and zeta potential of silver nanoparticles were detected by Zetasizer Nano. The average size of AgNPs (2 nm) observably increased the cellular uptake by endocytosis. AgNPs markedly inhibited the proliferation of HePG-2 cells through induction of apoptosis with caspase-3 activation and PARP cleavage. AgNPs with dose-dependent manner significantly increased the apoptotic cell population (sub-G1). Furthermore, AgNP-induced apoptosis was found dependent on the overproduction of reactive oxygen species (ROS) and affecting of MAPKs and AKT signaling and DNA damage-mediated p53 phosphorylation to advance HePG-2 cells apoptosis. Therefore, our results show that the mechanism of ROS-mediated signaling pathways may provide useful information in AgNP-induced HePG-2 cell apoptosis.

[Clinical utility of real-time fluorescent PCR for combined detection of anaplastic lymphoma kinase and c-ros oncogene 1 receptor tyrosine kinase in non-small cell lung cancer].

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Bai, D Y; Zhang, H P; Zhong, S; Suo, W H; Gao, D H; Ding, Y; Tu, J H

2016-12-23

Objective: To investigate the clinical application value of combined detection of ALK fusion gene and c-ros oncogene 1 receptor tyrosine kinase (ROS1) fusion gene in non-small cell lung cancer (NSCLC) using real-time fluorescent PCR. Methods: A kit for combined detection of ALK fusion gene and ROS1 fusion gene based on fluorescent PCR was used to simultaneously detect the two fusion genes in 302 cases of NSCLC specimens. The results were validated through Sanger sequencing. The consistency of the two detection methods was analyzed. Results: All 302 cases of NSCLC specimens were successfully analyzed through fluorescent PCR (302/302). 12 cases (4.0%) were found to contain ALK fusion gene, including 3 cases with ALK-M1, 3 with ALK-M2, 3 with ALK-M3, 1 with ALK-M4, and 2 with ALK-M6 fusion gene.12 cases (4.0%) were found to contain ROS1 fusion gene, including 1 case with ROS1-M7, 8 cases with ROS1-M8, 1 case with ROS1-M12, 1 case with ROS1-M14, and 1 case with double-positive ROS1-M3 and ROS1-M8 fusion genes. The total detection rate of ALK fusion gene and ROS1 fusion gene was 7.9% (24/302) and 278 cases showed to be negative for ALK fusion gene and ROS1 fusion gene. The successful detection rates for Sanger DNA sequencing were also 100%. The positive, negative and total coincidence rates obtained by real-time fluorescent PCR and by Sanger DNA sequencing were all 100%. Conclusions: The results of Sanger DNA sequencing demonstrate that the real-time fluorescent PCR assay is equally effective in detecting ALK and ROS1 fusion genes in NSCLC tissues. Furthermore, real-time fluorescent PCR assay can be used to detect trace ALK and ROS1 fusion gene simultaneously in tiny samples, and can save time and avoid repeated sampling. It is worthy of recommendation as a rapid and reliable detection technique.

Protectin DX, a double lipoxygenase product of DHA, inhibits both ROS production in human neutrophils and cyclooxygenase activities

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Liu, Miao; Boussetta, Tarek; Makni-Maalej, Karama; Fay, Michèle; Driss, Fathi; El-Benna, Jamel; Lagarde, Michel; Guichardant, Michel

2014-01-01

Neutrophils play a major role in inflammation by releasing large amounts of reactive oxygen species (ROS) produced by NADPH oxidase (NOX) and myeloperoxidase (MPO). This ROS overproduction is mediated by phosphorylation of the NOX subunits with an uncontrolled manner. Therefore, targeting neutrophil subunits would represent a promising strategy to moderate NOX activity, lower ROS, and other inflammatory agents, such as cytokines and leukotrienes, produced by neutrophils. For this purpose, we investigated the effects of protectin DX (PDX) - a docosahexaenoic acid (DHA) di-hydroxylated product which inhibits blood platelet aggregation - on neutrophil activation in vitro. We found that PDX decreases ROS production, inhibits NOX activation and MPO release from neutrophils. We also confirm, that PDX is an anti-aggregatory and anti-inflammatory agent by inhibiting both cyclooxygenase-1 and -2 (COX-1 and COX-2, E.C. 1.14.99.1) as well as COX-2 in lipopolysaccharides (LPS)-treated human neutrophils. However, PDX has no effect on the 5-lipoxygenase pathway that produces the chemotactic agent leukotriene B4 (LTB4). Taken together, our results suggest that PDX could be a protective agent against neutrophil invasion in chronic inflammatory diseases. PMID:24254970

N-acetylcysteine attenuates hexavalent chromium-induced hypersensitivity through inhibition of cell death, ROS-related signaling and cytokine expression.

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Yu-Hsuan Lee

Full Text Available Chromium hypersensitivity (chromium-induced allergic contact dermatitis is an important issue in occupational skin disease. Hexavalent chromium (Cr (VI can activate the Akt, Nuclear factor κB (NF-κB, and Mitogen-activated protein kinase (MAPK pathways and induce cell death, via the effects of reactive oxygen species (ROS. Recently, cell death stimuli have been proposed to regulate the release of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α and interleukin-1 (IL-1. However, the exact effects of ROS on the signaling molecules and cytotoxicity involved in Cr(VI-induced hypersensitivity have not yet been fully demonstrated. N-acetylcysteine (NAC could increase glutathione levels in the skin and act as an antioxidant. In this study, we investigated the effects of NAC on attenuating the Cr(VI-triggered ROS signaling in both normal keratinocyte cells (HaCaT cells and a guinea pig (GP model. The results showed the induction of apoptosis, autophagy and ROS were observed after different concentrations of Cr(VI treatment. HaCaT cells pretreated with NAC exhibited a decrease in apoptosis and autophagy, which could affect cell viability. In addition, Cr (VI activated the Akt, NF-κB and MAPK pathways thereby increasing IL-1α and TNF-α production. However, all of these stimulation phenomena could be inhibited by NAC in both of in vitro and in vivo studies. These novel findings indicate that NAC may prevent the development of chromium hypersensitivity by inhibiting of ROS-induced cell death and cytokine expression.

Chemically Regulated ROS Generation from Gold Nanoparticles for Enzyme-Free Electrochemiluminescent Immunosensing.

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Higashi, Yui; Mazumder, Joyotu; Yoshikawa, Hiroyuki; Saito, Masato; Tamiya, Eiichi

2018-04-17

In the present work, we report on an enzyme-free electrochemiluminescent (ECL) immunosensing scheme utilizing the catalytic generation of reactive oxygen species (ROS) from gold nanoparticles (AuNPs) (diameter ≥5 nm) dispersed in aqueous solutions of trishydroxymethylaminomethane (Tris). First, to examine this catalytic pathway in detail, the effects of various factors such as the AuNP size and concentration, dispersant type and concentration, and dissolved oxygen were investigated using the electrochemiluminescence (ECL) of luminol. It was found that the catalytic generation of ROS from AuNPs can be regulated chemically by altering conditions such as the type, concentration, and pH of the solution that the AuNPs are dispersed in. Under the best conditions studied in this work, the AuNPs displayed high catalytic activity toward ROS generation, with an estimated apparent turnover number per AuNP of 0.1 s -1 , comparable to those of several common peroxide-producing enzymes. Following these studies, this phenomenon was applied to develop a one-step enzyme-free ECL immunosensor based on sandwiching the target analyte using antibody-conjugated magnetic beads (MB) and AuNPs. Using IgA as a model analyte, the developed immunosensor was able to detect the target in the range of 1 ng/mL to 10 μg/mL, with the lower detection limit being comparable to those of commercial assays for the same target. Altering the antibodies used to modify the MB and AuNPs could further improve the detection limit as well as expand the applicability of this immunoassay to the detection of other analytes.

Edaravone, an ROS Scavenger, Ameliorates Photoreceptor Cell Death after Experimental Retinal Detachment

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Roh, Mi In; Murakami, Yusuke; Thanos, Aristomenis; Miller, Joan W.

2011-01-01

Purpose. To investigate whether edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, would be neuroprotective against photoreceptor cell death in a rat model of retinal detachment (RD). Methods. RD was induced in adult Brown Norway rats by subretinal injection of sodium hyaluronate. Edaravone (3, 5, or 10 mg/kg) or physiologic saline was administered intraperitoneally once a day until death on day 3 or 5. Oxidative stress in the retina was assessed by 4-hydroxynonenal staining or ELISA for protein carbonyl content. Photoreceptor death was assessed by TUNEL and measurement of the outer nuclear layer thickness. Western blot analysis and caspase activity assays were performed. Inflammatory cytokine secretion and inflammatory cell infiltration were evaluated by ELISA and immunostaining, respectively. Results. RD resulted in increased generation of ROS. Treatment with 5 mg/kg edaravone significantly reduced the ROS level, along with a decrease in TUNEL-positive cells in the photoreceptor layer. A caspase assay also confirmed decreased activation of caspase-3, -8, and -9 in RD treated with edaravone. The level of the antiapoptotic Bcl-2 was increased in detached retinas after edaravone treatment, whereas the levels of the stress-activated p-ERK1/2 were decreased. In addition, edaravone treatment resulted in a significant decrease in the levels of TNF-α, MCP-1, and macrophage infiltration. Conclusions. Oxidative stress plays an important role in photoreceptor cell death after RD. Edaravone treatment may aid in preventing photoreceptor cell death after RD by suppressing ROS-induced photoreceptor damage. PMID:21310909

Potential Use of Spin Traps to Control ROS in Antipollution Cosmetics—A Review

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Prashant D. Sawant

2018-01-01

Full Text Available Pollution from air and sunlight has adverse effects on human health, particularly skin health. It creates oxidative stress, which results in skin diseases, including skin cancer and aging. Different types of antioxidants are used as preventative actives in skin-care products. However, they have some limitations as they also scavenge oxygen. Recently, spin traps are being explored to trap free radicals before these radicals generating more free radicals (cascading effect and not the oxygen molecules. However, not all spin traps can be used in the topical cosmetic skin-care products due to their toxicity and regulatory issues. The present review focuses on the different pathways of reactive oxygen species (ROS generation due to pollution and the potential use of spin traps in anti-pollution cosmetics to control ROS.

Practical consensus recommendations on management of HR + ve early breast cancer with specific reference to genomic profiling

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S Aggarwal

2018-01-01

Full Text Available Breast cancer is a heterogeneous disease and patients are managed clinically based on ER, PR, HER2 expression, and key risk factors. The use of gene expression assays for early stage disease is already common practice. These tests have found a place in risk stratifying the heterogeneous group of stage I–II breast cancers for recurrence, for predicting chemotherapy response, and for predicting breast cancer-related mortality. Most guidelines for hormone receptor (HR–positive early breast cancer recommend addition of adjuvant chemotherapy for most women, leading to overtreatment, which causes considerable morbidity and cost. Expert oncologist discussed about strategies of gene expression assays and aid in chemotherapy recommendations for treatment of HR + ve EBC and the expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer.

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Zou, Peng; Chen, Minxiao; Ji, Jiansong; Chen, Weiqian; Chen, Xi; Ying, Shilong; Zhang, Junru; Zhang, Ziheng; Liu, Zhiguo; Yang, Shulin; Liang, Guang

2015-11-03

Gastric cancer (GC) is one of the leading causes of cancer mortality in the world. In addressing the need of treatments for relapsed disease, we report the identification of an existing U.S. Food and Drug Administration-approved small-molecule drug to repurpose for GC treatment. Auranofin (AF), clinically used to treat rheumatic arthritis, but it exhibited preclinical efficacy in GC cells. By increasing intracellular reactive oxygen species (ROS) levels, AF induces a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in cultured GC cells. Blockage of ROS production reversed AF-induced ER stress and mitochondrial pathways activation as well as apoptosis. In addition, AF displays synergistic lethality with an ROS-generating agent piperlongumine, which is a natural product isolated from the long pepper Piper longum L. Taken together, this work provides a novel anticancer candidate for the treatment of gastric cancer. More importantly, it reveals that increased ROS generation might be an effective strategy in treating human gastric cancer.

Can Orthopedic Oncologists Predict Functional Outcome in Patients with Sarcoma after Limb Salvage Surgery in the Lower Limb? A Nationwide Study

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Sjoerd Kolk

2014-01-01

Full Text Available Accurate predictions of functional outcome after limb salvage surgery (LSS in the lower limb are important for several reasons, including informing the patient preoperatively and, in some cases, deciding between amputation and LSS. This study aimed to elucidate the correlation between surgeon-predicted and patient-reported functional outcome of LSS in the Netherlands. Twenty-three patients (between six months and ten years after surgery and five independent orthopedic oncologists completed the Toronto Extremity Salvage Score (TESS and the RAND-36 physical functioning subscale (RAND-36 PFS. The orthopedic oncologists made their predictions based on case descriptions (including MRI scans that reflected the preoperative status. The correlation between patient-reported and surgeon-predicted functional outcome was “very poor” to “poor” on both scores (r2 values ranged from 0.014 to 0.354. Patient-reported functional outcome was generally underestimated, by 8.7% on the TESS and 8.3% on the RAND-36 PFS. The most difficult and least difficult tasks on the RAND-36 PFS were also the most difficult and least difficult to predict, respectively. Most questions had a “poor” intersurgeon agreement. It was difficult to accurately predict the patient-reported functional outcome of LSS. Surgeons’ ability to predict functional scores can be improved the most by focusing on accurately predicting more demanding tasks.

Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase-derived prostanoids.

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Diniz, Mariana C; Olivon, Vania C; Tavares, Lívia D; Simplicio, Janaina A; Gonzaga, Natália A; de Souza, Daniele G; Bendhack, Lusiane M; Tirapelli, Carlos R; Bonaventura, Daniella

2017-05-01

To determine the role of reactive oxygen species (ROS) on sodium nitroprusside (SNP)-induced tolerance. Additionally, we evaluated the role of ROS on NF-κB activation and pro-inflammatory cytokines production during SNP-induced tolerance. To induce in vitro tolerance, endothelium-intact or -denuded aortic rings isolated from male Balb-c mice were incubated for 15, 30, 45 or 60min with SNP (10nmol/L). Tolerance to SNP was observed after incubation of endothelium-denuded, but not endothelium-intact aortas for 60min with this inorganic nitrate. Pre-incubation of denuded rings with tiron (superoxide anion (O 2 - ) scavenger), and the NADPH oxidase inhibitors apocynin and atorvastatin reversed SNP-induced tolerance. l-NAME (non-selective NOS inhibitor) and l-arginine (NOS substrate) also prevented SNP-induced tolerance. Similarly, ibuprofen (non-selective cyclooxygenase (COX) inhibitor), nimesulide (selective COX-2 inhibitor), AH6809 (prostaglandin PGF 2 α receptor antagonist) or SQ29584 [PGH 2 /thromboxane TXA 2 receptor antagonist] reversed SNP-induced tolerance. Increased ROS generation was detected in tolerant arteries and both tiron and atorvastatin reversed this response. Tiron prevented tolerance-induced increase on O 2 - and hydrogen peroxide (H 2 O 2 ) levels. The increase onp65/NF-κB expression and TNF-α production in tolerant arteries was prevented by tiron. The major new finding of our study is that SNP-induced tolerance is mediated by NADPH-oxidase derived ROS and vasoconstrictor prostanoids derived from COX-2, which are capable of reducing the vasorelaxation induced by SNP. Additionally, we found that ROS mediate the activation of NF-κB and the production of TNF-α in tolerant arteries. These findings identify putative molecular mechanisms whereby SNP induces tolerance in the vasculature. Copyright © 2017 Elsevier Inc. All rights reserved.

IAEA Syllabus for the Education and Training of Radiation Oncologists. Endorsed by the American Society for Radiation Oncology (ASTRO) and the European Society for Therapeutic Radiology and Oncology (ESTRO)

International Nuclear Information System (INIS)

2009-01-01

Cancer is one of the leading causes of death globally and cancer incidence is predicted to increase, especially in developing countries. Almost 13% of all deaths worldwide are caused by cancer. In 2005, there were more than 7.6 million cancer deaths worldwide and 10 million newly diagnosed cases of cancer. Today there are more new cancer cases every year in lowmiddle income (LMI) countries than in industrialized countries, and cancer rates are projected to increase significantly in developing countries. By 2020, two-thirds of the projected 10 million annual cancer deaths will be in developing countries. Radiotherapy plays a fundamental role in the continuum of cancer care. However, this technology is not comprehensively provided and in some countries not provided at all. According to the IAEA's Directory of Radiotherapy Centers (DIRAC), as of January 2004 there were about 2000 radiotherapy centres in the developing world with fewer than 2500 teletherapy machines dedicated to cancer therapy. The deficit is not just one of machines - each radiotherapy facility needs trained staff (radiation oncologists, medical physicists, technologists, radiation oncology nurses and maintenance engineers) as well as appropriate arrangements for radiation protection, safety, security and a continuing and ongoing effort to ensure the quality of the radiotherapy process. Strengthening the capability of ministries of health and other health sector institutions for assessing options, formulating policies, and setting priorities is also crucial. The International Atomic Energy Agency (IAEA) has been assisting its Member States in the establishment, operation and upgrading of radiation oncology facilities for many years. Human resource development, which includes training of radiation oncologists, medical physicists, radiation therapy technologists and radiation oncology nurses, is an integral part of the assistance as shortage of such trained professionals would be a serious obstacle to

A semiautomatic CT-based ensemble segmentation of lung tumors: comparison with oncologists' delineations and with the surgical specimen.

Science.gov (United States)

Rios Velazquez, Emmanuel; Aerts, Hugo J W L; Gu, Yuhua; Goldgof, Dmitry B; De Ruysscher, Dirk; Dekker, Andre; Korn, René; Gillies, Robert J; Lambin, Philippe

2012-11-01

To assess the clinical relevance of a semiautomatic CT-based ensemble segmentation method, by comparing it to pathology and to CT/PET manual delineations by five independent radiation oncologists in non-small cell lung cancer (NSCLC). For 20 NSCLC patients (stages Ib-IIIb) the primary tumor was delineated manually on CT/PET scans by five independent radiation oncologists and segmented using a CT based semi-automatic tool. Tumor volume and overlap fractions between manual and semiautomatic-segmented volumes were compared. All measurements were correlated with the maximal diameter on macroscopic examination of the surgical specimen. Imaging data are available on www.cancerdata.org. High overlap fractions were observed between the semi-automatically segmented volumes and the intersection (92.5±9.0, mean±SD) and union (94.2±6.8) of the manual delineations. No statistically significant differences in tumor volume were observed between the semiautomatic segmentation (71.4±83.2 cm(3), mean±SD) and manual delineations (81.9±94.1 cm(3); p=0.57). The maximal tumor diameter of the semiautomatic-segmented tumor correlated strongly with the macroscopic diameter of the primary tumor (r=0.96). Semiautomatic segmentation of the primary tumor on CT demonstrated high agreement with CT/PET manual delineations and strongly correlated with the macroscopic diameter considered as the "gold standard". This method may be used routinely in clinical practice and could be employed as a starting point for treatment planning, target definition in multi-center clinical trials or for high throughput data mining research. This method is particularly suitable for peripherally located tumors. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

SirT1 knockdown potentiates radiation-induced bystander effect through promoting c-Myc activity and thus facilitating ROS accumulation

International Nuclear Information System (INIS)

Xie, Yuexia; Tu, Wenzhi; Zhang, Jianghong; He, Mingyuan; Ye, Shuang; Dong, Chen; Shao, Chunlin

2015-01-01

Highlights: • γ-Irradiation induced bystander effects between hepatoma cells and hepatocyte cells. • SirT1 played a protective role in regulating this bystander effect. • SirT1 contributed to the protective effects via elimination the accumulation of ROS. • The activity of c-Myc is critical for maintaining the protective role of SirT1. - Abstract: Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the bystander signaling processes, especially under hypoxic condition, are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 and SK-Hep-1 cells under either normoxia or hypoxia. This bystander response was dramatically diminished or enhanced when the SirT1 gene of irradiated hepatoma cells was overexpressed or knocked down, respectively, especially under hypoxia. Meanwhile, SirT1 knockdown promoted transcriptional activity for c-Myc and facilitated ROS accumulation. But both of the increased bystander responses and ROS generation due to SirT1-knockdown were almost completely suppressed by c-Myc interference. Moreover, ROS scavenger effectively abolished the RIBE triggered by irradiated hepatoma cells even with SirT1 depletion. These findings provide new insights that SirT1 has a profound role in regulating RIBE where a c-Myc-dependent release of ROS may be involved

SirT1 knockdown potentiates radiation-induced bystander effect through promoting c-Myc activity and thus facilitating ROS accumulation

Energy Technology Data Exchange (ETDEWEB)

Xie, Yuexia [Institute of Radiation Medicine, Fudan University, Shanghai (China); Central Laboratory, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai (China); Tu, Wenzhi; Zhang, Jianghong; He, Mingyuan; Ye, Shuang; Dong, Chen [Institute of Radiation Medicine, Fudan University, Shanghai (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, Shanghai (China)

2015-02-15

Highlights: • γ-Irradiation induced bystander effects between hepatoma cells and hepatocyte cells. • SirT1 played a protective role in regulating this bystander effect. • SirT1 contributed to the protective effects via elimination the accumulation of ROS. • The activity of c-Myc is critical for maintaining the protective role of SirT1. - Abstract: Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the bystander signaling processes, especially under hypoxic condition, are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 and SK-Hep-1 cells under either normoxia or hypoxia. This bystander response was dramatically diminished or enhanced when the SirT1 gene of irradiated hepatoma cells was overexpressed or knocked down, respectively, especially under hypoxia. Meanwhile, SirT1 knockdown promoted transcriptional activity for c-Myc and facilitated ROS accumulation. But both of the increased bystander responses and ROS generation due to SirT1-knockdown were almost completely suppressed by c-Myc interference. Moreover, ROS scavenger effectively abolished the RIBE triggered by irradiated hepatoma cells even with SirT1 depletion. These findings provide new insights that SirT1 has a profound role in regulating RIBE where a c-Myc-dependent release of ROS may be involved.

From will to live to will to die: oncologists, nurses, and social workers identification of suicidality in cancer patients.

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Granek, Leeat; Nakash, Ora; Ariad, Samuel; Chen, Wendy; Birenstock-Cohen, Shira; Shapira, Shahar; Ben-David, Merav

2017-12-01

The purpose of this research was to examine how oncologists, nurses, and social workers identify suicidality in cancer patients. Sixty-one healthcare professionals (23 oncologists, 18 social workers, and 20 nurses) at two academic cancer centers were interviewed using an in-depth interview guide. This was a qualitative study based on grounded theory methodology. Analysis involved line-by-line coding, with categories and themes emerging from participants' narratives. Suicidality in cancer patients exists on a wide spectrum that ranges from an active will to live to an active will to die. Four phases were identified that included: (A) a strong will to live expressed in themes of active treatments, seeking second opinions, overtreatment, and alternative treatments; (B) a decreasing will to live indicated in themes of mental health distress and physical pain and suffering; (C) a readiness to die expressed in themes of mental health distress, previous mental health diagnoses, physical pain, avoiding more suffering, preserving quality of life in old age, nearing end of life, lack of social support, and maintaining a sense of control; and (D) a will to die indicated in themes of euthanasia and active suicidality. Suicidality in cancer patients exists on a continuum. Cancer patients fluctuate on this spectrum depending on circumstances such as degree of suffering, their personalities and life circumstances, and whether they are nearing the end of life. Results of the study emphasize the need to collect more context specific data on suicidality among cancer patients and the importance of early integration of psychosocial and palliative care in the cancer treatment trajectory.

Asperlin induces G2/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells

International Nuclear Information System (INIS)

He, Long; Nan, Mei-Hua; Oh, Hyun Cheol; Kim, Young Ho; Jang, Jae Hyuk; Erikson, Raymond Leo; Ahn, Jong Seog; Kim, Bo Yeon

2011-01-01

Highlights: → A new anti-cancer effect of an antibiotics, asperlin, is exploited. → Asperlin induced human cervical cancer cell apoptosis through ROS generation. → Asperlin activated DNA-damage related ATM protein and cell cycle associated proteins. → Asperlin could be developed as a new anti-cancer therapeutics. -- Abstract: We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.

Mechanism of Cisplatin-Induced Cytotoxicity Is Correlated to Impaired Metabolism Due to Mitochondrial ROS Generation.

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Choi, Yong-Min; Kim, Han-Kyul; Shim, Wooyoung; Anwar, Muhammad Ayaz; Kwon, Ji-Woong; Kwon, Hyuk-Kwon; Kim, Hyung Joong; Jeong, Hyobin; Kim, Hwan Myung; Hwang, Daehee; Kim, Hyung Sik; Choi, Sangdun

2015-01-01

The chemotherapeutic use of cisplatin is limited by its severe side effects. In this study, by conducting different omics data analyses, we demonstrated that cisplatin induces cell death in a proximal tubular cell line by suppressing glycolysis- and tricarboxylic acid (TCA)/mitochondria-related genes. Furthermore, analysis of the urine from cisplatin-treated rats revealed the lower expression levels of enzymes involved in glycolysis, TCA cycle, and genes related to mitochondrial stability and confirmed the cisplatin-related metabolic abnormalities. Additionally, an increase in the level of p53, which directly inhibits glycolysis, has been observed. Inhibition of p53 restored glycolysis and significantly reduced the rate of cell death at 24 h and 48 h due to p53 inhibition. The foremost reason of cisplatin-related cytotoxicity has been correlated to the generation of mitochondrial reactive oxygen species (ROS) that influence multiple pathways. Abnormalities in these pathways resulted in the collapse of mitochondrial energy production, which in turn sensitized the cells to death. The quenching of ROS led to the amelioration of the affected pathways. Considering these observations, it can be concluded that there is a significant correlation between cisplatin and metabolic dysfunctions involving mROS as the major player.

Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis.

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Xingxing Kong

2010-07-01

Full Text Available Sirtuin 3 (SIRT3 is one of the seven mammalian sirtuins, which are homologs of the yeast Sir2 gene. SIRT3 is the only sirtuin with a reported association with the human life span. Peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha plays important roles in adaptive thermogenesis, gluconeogenesis, mitochondrial biogenesis and respiration. PGC-1alpha induces several key reactive oxygen species (ROS-detoxifying enzymes, but the molecular mechanism underlying this is not well understood.Here we show that PGC-1alpha strongly stimulated mouse Sirt3 gene expression in muscle cells and hepatocytes. Knockdown of PGC-1alpha led to decreased Sirt3 gene expression. PGC-1alpha activated the mouse SIRT3 promoter, which was mediated by an estrogen-related receptor (ERR binding element (ERRE (-407/-399 mapped to the promoter region. Chromatin immunoprecipitation and electrophoretic mobility shift assays confirmed that ERRalpha bound to the identified ERRE and PGC-1alpha co-localized with ERRalpha in the mSirt3 promoter. Knockdown of ERRalpha reduced the induction of Sirt3 by PGC-1alpha in C(2C(12 myotubes. Furthermore, Sirt3 was essential for PGC-1alpha-dependent induction of ROS-detoxifying enzymes and several components of the respiratory chain, including glutathione peroxidase-1, superoxide dismutase 2, ATP synthase 5c, and cytochrome c. Overexpression of SIRT3 or PGC-1alpha in C(2C(12 myotubes decreased basal ROS level. In contrast, knockdown of mSIRT3 increased basal ROS level and blocked the inhibitory effect of PGC-1alpha on cellular ROS production. Finally, SIRT3 stimulated mitochondrial biogenesis, and SIRT3 knockdown decreased the stimulatory effect of PGC-1alpha on mitochondrial biogenesis in C(2C(12 myotubes.Our results indicate that Sirt3 functions as a downstream target gene of PGC-1alpha and mediates the PGC-1alpha effects on cellular ROS production and mitochondrial biogenesis. Thus, SIRT3 integrates cellular energy

Arctigenin induces apoptosis in colon cancer cells through ROS/p38MAPK pathway.

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Li, Qing-chun; Liang, Yun; Tian, Yuan; Hu, Guang-rui

2016-01-01

In the current study the antiproliferative effect of arctigenin, plant lignin, was evaluated on human colon cancer cell line HT-29. Furthermore, attempts were made to explore the signaling mechanism which may be responsible for its effect. Cell growth inhibition was assessed by MTT and LDH assays. Flow cytometric analysis was performed to determine cell arrest in the cell cycle phase and apoptosis. Furthermore, to confirm the apoptotic activity of arctigenin, caspase-9 and -3 activities analysis was performed. The levels of reactive oxygen species (ROS) and p38 mitogen activated protein kinase (MAPK) were investigated to determine their role in inducing apoptosis in arctigenin-treated HT-29 colon cancer cell line. MTT and LDH results demonstrated significant cell growth inhibitory effect of arctigenin on HT-29 cells in a dose-dependent manner. Furthermore, increase in cell number arrested at G2/M phase was observed in flow cytometric analysis upon arctigenin treatment. In addition, arctigenin increased the apoptotic ratio in a dose-dependent manner. The involvement of intrinsic apoptotic pathway was indicated by the activation of caspase-9 and -3. Moreover, increased ROS production, activation of p38 MAPK and changes in mitochondrial membrane potential (ΔΨm) also revealed the role of intrinsic apoptotic signaling pathway in cell growth inhibition after arctigenin exposure. Arctigenin induces apoptosis in HT-29 colon cancer cells by regulating ROS and p38 MAPK pathways.

Role of ROS-mediated autophagy in radiation-induced bystander effect of hepatoma cells.

Science.gov (United States)

Wang, Xiangdong; Zhang, Jianghong; Fu, Jiamei; Wang, Juan; Ye, Shuang; Liu, Weili; Shao, Chunlin

2015-05-01

Autophagy plays a crucial role in cellular response to ionizing radiation, but it is unclear whether autophagy can modulate radiation-induced bystander effect (RIBE). Here, we investigated the relationship between bystander damage and autophagy in human hepatoma cells of HepG2. HepG2 cells were treated with conditioned medium (CM) collected from 3 Gy γ-rays irradiated hepatoma HepG2 cells for 4, 12, or 24 h, followed by the measurement of micronuclei (MN), intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and protein expressions of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 in the bystander HepG2 cells. In some experiments, the bystander HepG2 cells were respectively transfected with LC3 small interfering RNA (siRNA), Beclin-1 siRNA or treated with 1% dimethyl sulfoxide (DMSO). Additional MN and mitochondrial dysfunction coupled with ROS were induced in the bystander cells. The expressions of protein markers of autophagy, LC3-II/LC3-I and Beclin-1, increased in the bystander cells. The inductions of bystander MN and overexpressions of LC3 and Beclin-1 were significantly diminished by DMSO. However, when the bystander cells were transfected with LC3 siRNA or Beclin-1 siRNA, the yield of bystander MN was significantly enhanced. The elevated ROS have bi-functions in balancing the bystander effects. One is to cause MN and the other is to induce protective autophagy.

Beyond the polymerase-γ theory: Production of ROS as a mode of NRTI-induced mitochondrial toxicity.

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Reuben L Smith

Full Text Available Use of some HIV-1 nucleoside reverse transcriptase inhibitors (NRTI is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to specific NRTIs has predominantly been assigned to mitochondrial polymerase-γ inhibition by NRTIs. However, an increasing amount of data suggests that this is not the sole mechanism. Many NRTI induced adverse events have been linked to the incurrence of oxidative stress, although the causality of events leading to reactive oxygen species (ROS production and their role in toxicity is unclear. In this study we show that short-term effects of first generation NRTIs, which are rarely discussed in the literature, include inhibition of oxygen consumption, decreased ATP levels and increased ROS production. Collectively these events affect fitness and longevity of C. elegans through mitohormetic signalling events. Furthermore, we demonstrate that these effects can be normalized by addition of the anti-oxidant N-acetylcysteine (NAC, which suggests that ROS likely influence the onset and severity of adverse events upon drug exposure.

Macranthoidin B Modulates Key Metabolic Pathways to Enhance ROS Generation and Induce Cytotoxicity and Apoptosis in Colorectal Cancer

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Xing Fan

2018-04-01

Full Text Available Background/Aims: Induction of oxidative stress and reactive oxygen species (ROS mediated-apoptosis have been utilized as effective strategies in anticancer therapy. Macranthoidin B (MB is a potent inducer of ROS-mediated apoptosis in cancer, but its mechanism of action is poorly understood. Method: Superoxide production with MB exposure in colorectal cancer (CRC cells was measured using lucigenin chemiluminescence and real-time PCR. MB’s inhibitory effect on proliferation and viability of CRC cells was determined by proliferation assays. MB’s effect on apoptosis of CRC cells was determined by Western blotting and annexin V-FITC/PI staining. MB’s effect on the growth of CRC xenografts in mice was assessed. An established metabolomics profiling platform combining ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS with gas chromatography-mass spectrometry (GC-MS was performed to determine MB’s effect on total metabolite variation in CRC cells. Results: We found that MB increases ROS generation via modulating key metabolic pathways. Using metabolomics profiling platform combining LC-MS with GC-MS, a total of 236 metabolites were identified in HCT-116 cells in which 31 metabolites were determined to be significantly regulated (p ≤ 0.05 after MB exposure. A number of key metabolites revealed by metabolomics analysis include glucose, fructose, citrate, arginine, phenylalanine, and S-adenosylhomocysteine (SAH, suggesting specific modulation of metabolism on carbohydrates, amino acids and peptides, lipids, nucleotide, cofactors and vitamins in HCT-116 CRC cells with MB treatment highly associated with apoptosis triggered by enhanced ROS and activated caspase-3. Conclusion: Our results demonstrate that MB represses CRC cell proliferation by inducing ROS-mediated apoptosis.

Macranthoidin B Modulates Key Metabolic Pathways to Enhance ROS Generation and Induce Cytotoxicity and Apoptosis in Colorectal Cancer.

Science.gov (United States)

Fan, Xing; Rao, Jun; Zhang, Ziwei; Li, Dengfeng; Cui, Wenhao; Zhang, Jun; Wang, Hua; Tou, Fangfang; Zheng, Zhi; Shen, Qiang

2018-01-01

Induction of oxidative stress and reactive oxygen species (ROS) mediated-apoptosis have been utilized as effective strategies in anticancer therapy. Macranthoidin B (MB) is a potent inducer of ROS-mediated apoptosis in cancer, but its mechanism of action is poorly understood. Superoxide production with MB exposure in colorectal cancer (CRC) cells was measured using lucigenin chemiluminescence and real-time PCR. MB's inhibitory effect on proliferation and viability of CRC cells was determined by proliferation assays. MB's effect on apoptosis of CRC cells was determined by Western blotting and annexin V-FITC/PI staining. MB's effect on the growth of CRC xenografts in mice was assessed. An established metabolomics profiling platform combining ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS) with gas chromatography-mass spectrometry (GC-MS) was performed to determine MB's effect on total metabolite variation in CRC cells. We found that MB increases ROS generation via modulating key metabolic pathways. Using metabolomics profiling platform combining LC-MS with GC-MS, a total of 236 metabolites were identified in HCT-116 cells in which 31 metabolites were determined to be significantly regulated (p ≤ 0.05) after MB exposure. A number of key metabolites revealed by metabolomics analysis include glucose, fructose, citrate, arginine, phenylalanine, and S-adenosylhomocysteine (SAH), suggesting specific modulation of metabolism on carbohydrates, amino acids and peptides, lipids, nucleotide, cofactors and vitamins in HCT-116 CRC cells with MB treatment highly associated with apoptosis triggered by enhanced ROS and activated caspase-3. Our results demonstrate that MB represses CRC cell proliferation by inducing ROS-mediated apoptosis. © 2018 The Author(s). Published by S. Karger AG, Basel.

T3SS effector VopL inhibits the host ROS response, promoting the intracellular survival of Vibrio parahaemolyticus.

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Marcela de Souza Santos

2017-06-01

Full Text Available The production of antimicrobial reactive oxygen species by the nicotinamide dinucleotide phosphate (NADPH oxidase complex is an important mechanism for control of invading pathogens. Herein, we show that the gastrointestinal pathogen Vibrio parahaemolyticus counteracts reactive oxygen species (ROS production using the Type III Secretion System 2 (T3SS2 effector VopL. In the absence of VopL, intracellular V. parahaemolyticus undergoes ROS-dependent filamentation, with concurrent limited growth. During infection, VopL assembles actin into non-functional filaments resulting in a dysfunctional actin cytoskeleton that can no longer mediate the assembly of the NADPH oxidase at the cell membrane, thereby limiting ROS production. This is the first example of how a T3SS2 effector contributes to the intracellular survival of V. parahaemolyticus, supporting the establishment of a protective intracellular replicative niche.

Development and validation of a medical chart review checklist for symptom management performance of oncologists in the routine care of patients with advanced cancer.

Science.gov (United States)

Blum, David; Rosa, Daniel; deWolf-Linder, Susanne; Hayoz, Stefanie; Ribi, Karin; Koeberle, Dieter; Strasser, Florian

2014-12-01

Oncologists perform a range of pharmacological and nonpharmacological interventions to manage the symptoms of outpatients with advanced cancer. The aim of this study was to develop and test a symptom management performance checklist (SyMPeC) to review medical charts. First, the content of the checklist was determined by consensus of an interprofessional team. The SyMPeC was tested using the data set of the SAKK 96/06 E-MOSAIC (Electronical Monitoring of Symptoms and Syndromes Associated with Cancer) trial, which included six consecutive visits from 247 patients. In a test data set (half of the data) of medical charts, two people extracted and quantified the definitions of the parameters (content validity). To assess the inter-rater reliability, three independent researchers used the SyMPeC on a random sample (10% of the test data set), and Fleiss's kappa was calculated. To test external validity, the interventions retrieved by the SyMPeC chart review were compared with nurse-led assessment of patient-perceived oncologists' palliative interventions. Five categories of symptoms were included: pain, fatigue, anorexia/nausea, dyspnea, and depression/anxiety. Interventions were categorized as symptom specific or symptom unspecific. In the test data set of 123 patients, 402 unspecific and 299 symptom-specific pharmacological interventions were detected. Nonpharmacological interventions (n = 242) were mostly symptom unspecific. Fleiss's kappa for symptom and intervention detections was K = 0.7 and K = 0.86, respectively. In 1003 of 1167 visits (86%), there was a match between SyMPeC and nurse-led assessment. Seventy-nine percent (195 of 247) of patients had no or one mismatch. Chart review by SyMPeC seems reliable to detect symptom management interventions by oncologists in outpatient clinics. Nonpharmacological interventions were less symptom specific. A template for documentation is needed for standardization. Copyright © 2014 American Academy of Hospice and

Human Mut T Homolog 1 (MTH1): a roadblock for the tumor-suppressive effects of oncogenic RAS-induced ROS.

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Rai, Priyamvada

2012-01-01

Oncogenic RAS-induced reactive oxygen species (ROS) trigger barriers to cell transformation and cancer progression through tumor-suppressive responses such as cellular senescence or cell death. We have recently shown that oncogenic RAS-induced DNA damage and attendant premature senescence can be prevented by overexpressing human MutT Homolog 1 (MTH1), the major mammalian detoxifier of the oxidized DNA precursor, 8-oxo-dGTP. Paradoxically, RAS-induced ROS are also able to participate in tumor progression via transformative processes such as mitogenic signaling, the epithelial-mesenchymal transition (EMT), anoikis inhibition, and PI3K/Akt-mediated survival signaling. Here we provide a preliminary insight into the influence of MTH1 levels on the EMT phenotype and Akt activation in RAS-transformed HMLE breast epithelial cells. Within this context, we will discuss the implications of MTH1 upregulation in oncogenic RAS-sustaining cells as a beneficial adaptive change that inhibits ROS-mediated cell senescence and participates in the maintenance of ROS-associated tumor-promoting mechanisms. Accordingly, targeting MTH1 in RAS-transformed tumor cells will not only induce proliferative defects but also potentially enhance therapeutic cytotoxicity by shifting cellular response away from pro-survival mechanisms.

Utilizing Robot Operating System (ROS) in Robot Vision and Control

Science.gov (United States)

2015-09-01

Palmer, “Development of a navigation system for semi-autonomous operation of wheelchairs,” in Proc. of the 8th IEEE/ASME Int. Conf. on Mechatronic ...and Embedded Systems and Applications, Suzhou, China, 2012, pp. 257-262. [30] G. Grisetti, C. Stachniss, and W. Burgard, “Improving grid-based SLAM...OPERATING SYSTEM (ROS) IN ROBOT VISION AND CONTROL by Joshua S. Lum September 2015 Thesis Advisor: Xiaoping Yun Co-Advisor: Zac Staples

Tunicamycin promotes apoptosis in leukemia cells through ROS generation and downregulation of survivin expression.

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Lim, Eun Jin; Heo, Jeonghoon; Kim, Young-Ho

2015-08-01

Tunicamycin (TN), one of the endoplasmic reticulum stress inducers, has been reported to inhibit tumor cell growth and exhibit anticarcinogenic activity. However, the mechanism by which TN initiates apoptosis remains poorly understood. In the present study, we investigated the effect of TN on the apoptotic pathway in U937 cells. We show that TN induces apoptosis in association with caspase-3 activation, generation of reactive oxygen species (ROS), and downregulation of survivin expression. P38 MAPK (mitogen-activated protein kinase) and the generation of ROS signaling pathway play crucial roles in TN-induced apoptosis in U937 cells. We hypothesized that TN-induced activation of p38 MAPK signaling pathway is responsible for cell death. To test this hypothesis, we selectively inhibited MAPK during treatment with TN. Our data demonstrated that inhibitor of p38 (SB), but not ERK (PD) or JNK (SP), partially maintained apoptosis during treatment with TN. Pre-treatment with NAC and GSH markedly prevented cell death, suggesting a role for ROS in this process. Ectopic expression of survivin in U937 cells attenuated TN-induced apoptosis by suppression of caspase-3 cleavage, mitochondrial membrane potential, and cytochrome c release in U937 cells. Taken together, our results show that TN modulates multiple components of the apoptotic response of human leukemia cells and raise the possibility of a novel therapeutic strategy for hematological malignancies.

RosUkrEnergo lubas piiluda rahamasina hämarasse sisemusse / Krister Paris

Index Scriptorium Estoniae

Paris, Krister, 1977-

2006-01-01

Ukrainasse gaasi vahendava RosUkrEnergo omanikke hoiti viimase ajani saladuses, nüüd on omanikering avalikustatud. Firmat seostatakse Venemaa väidetava esikurjategijaga. Briti mõttekoda Global Witness kutsub oma raportis Ukraina valitsust firmat põhjalikult uurima. Lisa: Salapärane miljardär ja gaasimängud

Adiponectin protects palmitic acid induced endothelial inflammation and insulin resistance via regulating ROS/IKKβ pathways.

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Zhao, Wenwen; Wu, Chuanhong; Li, Shaojing; Chen, Xiuping

2016-12-01

Endothelial inflammation and insulin resistance (IR) has been closely associated with endothelial dysfunction. Adiponectin (APN), an adipocyte-secreted hormone from adipose tissues, showed cardioprotective effects. Here, the protective effect of APN on palmitic acid (PA)-induced endothelial inflammation and IR was investigated. Cultured human umbilical vein endothelial cells (HUVECs) were treated with PA without or without APN pretreatment. The expression of inflammatory cytokines TNF-α, IL-6, adhesion molecule ICAM-1 were determined by western blotting, ELISA, and real-time PCR. The protein expression and protein-protein interaction were determined by western blotting and immunoprecipitation. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) production were monitored with fluorescence probes. PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1 at protein and mRNA levels, which was significantly inhibited by APN. PA treatment caused increase of ROS generation, NOX2, p-IKKβ, p-IκBα, p-p65 expression, and p-IκBα-IKKβ interaction, which were all partly reversed by APN. ROS scavenger N-acetylcysteine (NAC) and NF-κB inhibitor PDTC showed similar effect on PA-induced secretion of TNF-α, IL-6, and expression of ICAM-1. Furthermore, APN and NAC pretreatment restored PA-induced increase of p-IRS-1(S307), decrease of p-IRS-1(Tyr). In addition, insulin-triggered expression of p-IRS-1(Tyr), p-PI3K, p-AKT, p-eNOS and NO generation were inhibited by PA, which were also restored by both APN and NAC. These results suggested that APN ameliorated endothelial inflammation and IR through ROS/IKKβ pathway. This study shed new insights into the mechanisms of APN's cardiovascular protective effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

ROS enhancement by silicon nanoparticles in X-ray irradiated aqueous suspensions and in glioma C6 cells

International Nuclear Information System (INIS)

David Gara, Pedro M.; Garabano, Natalia I.; Llansola Portoles, Manuel J.; Moreno, M. Sergio; Dodat, Diego; Casas, Oscar R.; Gonzalez, Mónica C.; Kotler, Mónica L.

2012-01-01

The capability of silicon nanoparticles to increase the yield of reactive species upon 4 MeV X-ray irradiation of aqueous suspensions and C6 glioma cell cultures was investigated. ROS generation was detected and quantified using several specific probes. The particles were characterized by FTIR, XPS, TEM, DLS, luminescence, and adsorption spectroscopy before and after irradiation to evaluate the effect of high energy radiation on their structure. The total concentration of O 2 •− /HO 2 • , HO • , and H 2 O 2 generated upon 4-MeV X-ray irradiation of 6.4 μM silicon nanoparticle aqueous suspensions were on the order of 10 μM per Gy, ten times higher than that obtained in similar experiments but in the absence of particles. Cytotoxic 1 O 2 was generated only in irradiation experiments containing the particles. The particle surface became oxidized to SiO 2 and the luminescence yield reduced with the irradiation dose. Changes in the surface morphology did not affect, within the experimental error, the yields of ROS generated per Gy. X-ray irradiation of glioma C6 cell cultures with incorporated silicon nanoparticles showed a marked production of ROS proportional to the radiation dose received. In the absence of nanoparticles, the cells showed no irradiation-enhanced ROS generation. The obtained results indicate that silicon nanoparticles of 1 O 2 upon X-ray irradiation opens novel approaches in the design of therapy strategies.

d,l-Sulforaphane Induces ROS-Dependent Apoptosis in Human Gliomablastoma Cells by Inactivating STAT3 Signaling Pathway

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Ziwei Miao

2017-01-01

Full Text Available d,l-Sulforaphane (SFN, a synthetic analogue of broccoli-derived isomer l-SFN, exerts cytotoxic effects on multiple tumor cell types through different mechanisms and is more potent than the l-isomer at inhibiting cancer growth. However, the means by which SFN impairs glioblastoma (GBM cells remains poorly understood. In this study, we investigated the anti-cancer effect of SFN in GBM cells and determined the underlying molecular mechanisms. Cell viability assays, flow cytometry, immunofluorescence, and Western blot results revealed that SFN could induced apoptosis of GBM cells in a dose- and time-dependent manner, via up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2. Mechanistically, SFN treatment led to increase the intracellular reactive oxygen species (ROS level in GBM cells. Meanwhile, SFN also suppressed both constitutive and IL-6-induced phosphorylation of STAT3, and the activation of upstream JAK2 and Src tyrosine kinases, dose- and time-dependently. Moreover, blockage of ROS production by using the ROS inhibitor N-acetyl-l-cysteine totally reversed SFN-mediated down-regulation of JAK2/Src-STAT3 signaling activation and the subsequent effects on apoptosis by blocking the induction of apoptosis-related genes in GBM cells. Taken together, our data suggests that SFN induces apoptosis in GBM cells via ROS-dependent inactivation of STAT3 phosphorylation. These findings motivate further evaluation of SFN as a cancer chemopreventive agent in GBM treatment.

A High-Throughput UHPLC-QqQ-MS Method for Polyphenol Profiling in Rosé Wines

Directory of Open Access Journals (Sweden)

Marine Lambert

2015-04-01

Full Text Available A rapid, sensitive and selective analysis method using Ultra High Performance Liquid Chromatography coupled to triple-quadrupole Mass Spectrometry (UHPLC-QqQ-MS has been developed for the quantification of polyphenols in rosé wines. The compound detection being based on specific MS transitions in Multiple Reaction Monitoring (MRM mode, the present method allows the selective quantification of up to 152 phenolic and two additional non-phenolic wine compounds in 30 min without sample purification or pre-concentration, even at low concentration levels. This method was repeatably applied to a set of 12 rosé wines and thus proved to be suitable for high-throughput and large-scale metabolomics studies.

Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly (ADP-ribose) polymerase-1

OpenAIRE

Wang, Feng; Zhou, Xixi; Liu, Wenlan; Sun, Xi; Chen, Chen; Hudson, Laurie G.; Liu, Ke Jian

2013-01-01

Arsenic enhances genotoxicity of other carcinogenic agents such as ultraviolet radiation and benzo[a]pyrene. Recent reports suggest that inhibition of DNA repair is an important aspect of arsenic co-carcinogenesis, and DNA repair proteins such as poly (ADP ribose) polymerase (PARP)-1 are direct molecular targets of arsenic. Although arsenic has been shown to generate reactive oxygen/nitrogen species (ROS/RNS), little is known about the role of arsenic-induced ROS/RNS in the mechanism underlyi...

Dreams, themes and particle beams--an oncologist's perspective on technology trickle-down from the LHC.

Science.gov (United States)

Jena, R

2014-04-01

11 years ago, the European Network for Light Ion Therapy (ENLIGHT) was established as a multidisciplinary network of engineers, physicists and clinicians with a common interest in the development of hadron therapy in Europe. ENLIGHT is coordinated from the European Centre for Nuclear Research (CERN), the home of the Large Hadron Collider. The network has evolved into a mature platform for research, with more than 100 researchers working in CERN and its allied research centres. One of the benefits of hosting this network at CERN is the ability to translate hardware and software developments, originally developed in the High Energy Physics domain, into clinical applications. From the perspective of a clinical radiation oncologist within the network, this commentary reviews the ways in which leading edge technological developments in detectors and solid state physics, Monte-Carlo simulation, grid computing and accelerator design have trickled down into real-world clinical applications.

Trace amounts of Cu{sup 2+} ions influence ROS production and cytotoxicity of ZnO quantum dots

Energy Technology Data Exchange (ETDEWEB)

Moussa, Hatem [CNRS and Université de Lorraine, Laboratoire Réactions et Génie des Procédés (LRGP), CNRS UMR 7274, 1 rue Grandville, 54001 Nancy (France); Laboratoire de Biosurveillance de l' Environnement, Université de Carthage, Faculté des Sciences de Bizerte, 7021 Jarzouna, Bizerte (Tunisia); Merlin, Christophe [CNRS and Université de Lorraine, Laboratoire de Chimie Physique et Microbiologie pour l' Environnement (LCPME), CNRS UMR 7564, 15 Avenue du Charmois, 54500 Vandoeuvre-lès-Nancy (France); Dezanet, Clément [CNRS and Université de Lorraine, Laboratoire Réactions et Génie des Procédés (LRGP), CNRS UMR 7274, 1 rue Grandville, 54001 Nancy (France); Balan, Lavinia [Institut de Science des Matériaux de Mulhouse (IS2M), CNRS UMR 7361, 15 rue Jean Starcky, 68093 Mulhouse (France); Medjahdi, Ghouti [CNRS and Université de Lorraine, Institut Jean Lamour (IJL), UMR CNRS 7198, BP 70239, 54506 Vandoeuvre-lès-Nancy Cedex (France); Ben-Attia, Mossadok [Laboratoire de Biosurveillance de l' Environnement, Université de Carthage, Faculté des Sciences de Bizerte, 7021 Jarzouna, Bizerte (Tunisia); and others

2016-03-05

Highlights: • Chemisorbed Cu{sup 2+} ions on ZnO QDs enhance ROS production. • A mechanism combining excited electrons and holes and Fenton reactions is proposed. • ZnO@APTMS/Cu QDs were found to be the most deleterious to E. coli cells. - Abstract: 3-Aminopropyltrimethoxysilane (APTMS) was used as ligand to prepare ZnO@APTMS, Cu{sup 2+}-doped ZnO (ZnO:Cu@APTMS) and ZnO quantum dots (QDs) with chemisorbed Cu{sup 2+} ions at their surface (ZnO@APTMS/Cu). The dots have a diameter of ca. 5 nm and their crystalline and phase purities and composition were established by X-ray diffraction, transmission electron microscopy, UV-visible and fluorescence spectroscopies and by X-ray photoelectron spectroscopy. The effect of Cu{sup 2+} location on the ability of the QDs to generate reactive oxygen species (ROS) under light irradiation was investigated. Results obtained demonstrate that all dots are able to produce ROS (·OH, O{sub 2}·{sup −}, H{sub 2}O{sub 2} and {sup 1}O{sub 2}) and that ZnO@APTMS/Cu QDs generate more ·OH and O{sub 2}·{sup −} radicals and H{sub 2}O{sub 2} than ZnO@APTMS and ZnO:Cu@APTMS QDs probably via mechanisms associating photo-induced charge carriers and Fenton reactions. In cytotoxicity experiments conducted in the dark or under light exposure, ZnO@APTMS/Cu QDs appeared slightly more deleterious to Escherichia coli cells than the two other QDs, therefore pointing out the importance of the presence of Cu{sup 2+} ions at the periphery of the nanocrystals. On the other hand, with the lack of photo-induced toxicity, it can be inferred that ROS production cannot explain the cytotoxicity associated to the QDs. Our study demonstrates that both the production of ROS from ZnO QDs and their toxicity may be enhanced by chemisorbed Cu{sup 2+} ions, which could be useful for medical or photocatalytic applications.

Measurement of OH, NO, O and N atoms in helium plasma jet for ROS/RNS controlled biomedical processes

Science.gov (United States)

Yonemori, Seiya; Kamakura, Taku; Ono, Ryo

2014-10-01

Atmospheric-pressure plasmas are of emerging interest for new plasma applications such as cancer treatment, cell activation and sterilization. In those biomedical processes, reactive oxygen/nitrogen species (ROS/RNS) are said that they play significant role. It is though that active species give oxidative stress and induce biomedical reactions. In this study, we measured OH, NO, O and N atoms using laser induced fluorescence (LIF) measurement and found that voltage polarity affect particular ROS. When negative high voltage was applied to the plasma jet, O atom density was tripled compared to the case of positive applied voltage. In that case, O atom density was around 3 × 1015 [cm-3] at maximum. In contrast, OH and NO density did not change their density depending on the polarity of applied voltage, measured as in order of 1013 and 1014 [cm-3] at maximum, respectively. From ICCD imaging measurement, it could be seen that negative high voltage enhanced secondary emission in plasma bullet propagation and it can affect the effective production of particular ROS. Since ROS/RNS dose can be a quantitative criterion to control plasma biomedical application, those measurement results is able to be applied for in vivo and in vitro plasma biomedical experiments. This study is supported by the Grant-in-Aid for Science Research by the Ministry of Education, Culture, Sport, Science and Technology.

Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly(ADP-ribose) polymerase-1.

Science.gov (United States)

Wang, Feng; Zhou, Xixi; Liu, Wenlan; Sun, Xi; Chen, Chen; Hudson, Laurie G; Jian Liu, Ke

2013-08-01

Arsenic enhances the genotoxicity of other carcinogenic agents such as ultraviolet radiation and benzo[a]pyrene. Recent reports suggest that inhibition of DNA repair is an important aspect of arsenic cocarcinogenesis, and DNA repair proteins such as poly(ADP ribose) polymerase (PARP)-1 are direct molecular targets of arsenic. Although arsenic has been shown to generate reactive oxygen/nitrogen species (ROS/RNS), little is known about the role of arsenic-induced ROS/RNS in the mechanism underlying arsenic inhibition of DNA repair. We report herein that arsenite-generated ROS/RNS inhibits PARP-1 activity in cells. Cellular exposure to arsenite, as well as hydrogen peroxide and NONOate (nitric oxide donor), decreased PARP-1 zinc content, enzymatic activity, and PARP-1 DNA binding. Furthermore, the effects of arsenite on PARP-1 activity, DNA binding, and zinc content were partially reversed by the antioxidant ascorbic acid, catalase, and the NOS inhibitor, aminoguanidine. Most importantly, arsenite incubation with purified PARP-1 protein in vitro did not alter PARP-1 activity or DNA-binding ability, whereas hydrogen peroxide or NONOate retained PARP-1 inhibitory activity. These results strongly suggest that cellular generation of ROS/RNS plays an important role in arsenite inhibition of PARP-1 activity, leading to the loss of PARP-1 DNA-binding ability and enzymatic activity. Copyright © 2013 Elsevier Inc. All rights reserved.

Asperlin induces G{sub 2}/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

He, Long; Nan, Mei-Hua [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Oh, Hyun Cheol [College of Medical and Life Sciences, Silla University, 100 Silladaehak-gil, Sasang-gu, Busan 617-736 (Korea, Republic of); Kim, Young Ho [College of Pharmacy, ChungNam National University, Yuseong, Daejeon, 305-764 (Korea, Republic of); Jang, Jae Hyuk [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Erikson, Raymond Leo [Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 (United States); Ahn, Jong Seog, E-mail: jsahn@kribb.re.kr [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Kim, Bo Yeon, E-mail: bykim@kribb.re.kr [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); World Class Institute, KRIBB, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of)

2011-06-10

Highlights: {yields} A new anti-cancer effect of an antibiotics, asperlin, is exploited. {yields} Asperlin induced human cervical cancer cell apoptosis through ROS generation. {yields} Asperlin activated DNA-damage related ATM protein and cell cycle associated proteins. {yields} Asperlin could be developed as a new anti-cancer therapeutics. -- Abstract: We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.

PO2 Cycling Reduces Diaphragm Fatigue by Attenuating ROS Formation

OpenAIRE

Zuo, Li; Diaz, Philip T.; Chien, Michael T.; Roberts, William J.; Kishek, Juliana; Best, Thomas M.; Wagner, Peter D.

2014-01-01

Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monito...

ROS and CDPK-like kinase-mediated activation of MAP kinase in rice roots exposed to lead.

Science.gov (United States)

Huang, Tsai-Lien; Huang, Hao-Jen

2008-04-01

Lead (Pb2+) is a cytotoxic metal ion in plants, the mechanism of which is not yet established. The aim of this study is to investigate the signalling pathways that are activated by elevated concentrations of Pb2+ in rice roots. Root growth was stunted and cell death was accelerated when exposed to different dosages of Pb2+ during extended time periods. Using ROS-sensitive dye and Ca2+ indicator, we demonstrated that Pb2+ induced ROS production and Ca2+ accumulation, respectively. In addition, Pb2+ elicited a remarkable increase in myelin basic protein (MBP) kinase activities. By immunoblot and immunoprecipitation analysis, 40- and 42-kDa MBP kinases that were activated by Pb2+ were identified to be mitogen-activated protein (MAP) kinases. Pre-treatment of rice roots with an antioxidant and a NADPH oxidase inhibitor, glutathione (GSH) and diphenylene iodonium (DPI), effectively reduced Pb2+-induced cell death and MAP kinase activation. Moreover, calcium-dependent protein kinase (CDPK) antagonist, W7, attenuated Pb2+-induced cell death and MAP kinase activation. These results suggested that the ROS and CDPK may function in the Pb2+-triggered cell death and MAP kinase signalling pathway in rice roots.

IAEA Syllabus for the Education and Training of Radiation Oncologists. Endorsed by the American Society for Radiation Oncology (ASTRO) and the European Society for Therapeutic Radiology and Oncology (ESTRO) (Chinese Edition)

International Nuclear Information System (INIS)

2014-01-01

Cancer is one of the leading causes of death globally and cancer incidence is predicted to increase, especially in developing countries. Almost 13% of all deaths … worldwide are caused by cancer. In 2005, there were more than 7.6 million cancer deaths worldwide and 10 million newly diagnosed cases of cancer. Today there are more new cancer cases every year in lowmiddle income (LMI) countries than in industrialized countries, and cancer rates are projected to increase significantly in developing countries. By 2020, two-thirds of the projected 10 million annual cancer deaths will be in developing countries. Radiotherapy plays a fundamental role in the continuum of cancer care. However, this technology is not comprehensively provided and in some countries not provided at all. According to the IAEA's Directory of Radiotherapy Centers (DIRAC), as of January 2004 there were about 2000 radiotherapy centres in the developing world with fewer than 2500 teletherapy machines dedicated to cancer therapy. The deficit is not just one of machines - each radiotherapy facility needs trained staff (radiation oncologists, medical physicists, technologists, radiation oncology nurses and maintenance engineers) as well as appropriate arrangements for radiation protection, safety, security and a continuing and ongoing effort to ensure the quality of the radiotherapy process. Strengthening the capability of ministries of health and other health sector institutions for assessing options, formulating policies, and setting priorities is also crucial. The International Atomic Energy Agency (IAEA) has been assisting its Member States in the establishment, operation and upgrading of radiation oncology facilities for many years. Human resource development, which includes training of radiation oncologists, medical physicists, radiation therapy technologists and radiation oncology nurses, is an integral part of the assistance as shortage of such trained professionals would be a serious

IAEA Syllabus for the Education and Training of Radiation Oncologists. Endorsed by the American Society for Radiation Oncology (ASTRO) and the European Society for Therapeutic Radiology and Oncology (ESTRO) (French Edition)

International Nuclear Information System (INIS)

2013-01-01

Cancer is one of the leading causes of death globally and cancer incidence is predicted to increase, especially in developing countries. Almost 13% of all deaths worldwide are caused by cancer. In 2005, there were more than 7.6 million cancer deaths worldwide and 10 million newly diagnosed cases of cancer. Today there are more new cancer cases every year in lowmiddle income (LMI) countries than in industrialized countries, and cancer rates are projected to increase significantly in developing countries. By 2020, two-thirds of the projected 10 million annual cancer deaths will be in developing countries. Radiotherapy plays a fundamental role in the continuum of cancer care. However, this technology is not comprehensively provided and in some countries not provided at all. According to the IAEA's Directory of Radiotherapy Centers (DIRAC), as of January 2004 there were about 2000 radiotherapy centres in the developing world with fewer than 2500 teletherapy machines dedicated to cancer therapy. The deficit is not just one of machines - each radiotherapy facility needs trained staff (radiation oncologists, medical physicists, technologists, radiation oncology nurses and maintenance engineers) as well as appropriate arrangements for radiation protection, safety, security and a continuing and ongoing effort to ensure the quality of the radiotherapy process. Strengthening the capability of ministries of health and other health sector institutions for assessing options, formulating policies, and setting priorities is also crucial. The International Atomic Energy Agency (IAEA) has been assisting its Member States in the establishment, operation and upgrading of radiation oncology facilities for many years. Human resource development, which includes training of radiation oncologists, medical physicists, radiation therapy technologists and radiation oncology nurses, is an integral part of the assistance as shortage of such trained professionals would be a serious obstacle to

IAEA Syllabus for the Education and Training of Radiation Oncologists. Endorsed by the American Society for Radiation Oncology (ASTRO) and the European Society for Therapeutic Radiology and Oncology (ESTRO) (Spanish Edition)

International Nuclear Information System (INIS)

2014-01-01

Cancer is one of the leading causes of death globally and cancer incidence is predicted to increase, especially in developing countries. Almost 13% of all deaths worldwide are caused by cancer. In 2005, there were more than 7.6 million cancer deaths worldwide and 10 million newly diagnosed cases of cancer. Today there are more new cancer cases every year in lowmiddle income (LMI) countries than in industrialized countries, and cancer rates are projected to increase significantly in developing countries. By 2020, two-thirds of the projected 10 million annual cancer deaths will be in developing countries. Radiotherapy plays a fundamental role in the continuum of cancer care. However, this technology is not comprehensively provided and in some countries not provided at all. According to the IAEA's Directory of Radiotherapy Centers (DIRAC), as of January 2004 there were about 2000 radiotherapy centres in the developing world with fewer than 2500 teletherapy machines dedicated to cancer therapy. The deficit is not just one of machines - each radiotherapy facility needs trained staff (radiation oncologists, medical physicists, technologists, radiation oncology nurses and maintenance engineers) as well as appropriate arrangements for radiation protection, safety, security and a continuing and ongoing effort to ensure the quality of the radiotherapy process. Strengthening the capability of ministries of health and other health sector institutions for assessing options, formulating policies, and setting priorities is also crucial. The International Atomic Energy Agency (IAEA) has been assisting its Member States in the establishment, operation and upgrading of radiation oncology facilities for many years. Human resource development, which includes training of radiation oncologists, medical physicists, radiation therapy technologists and radiation oncology nurses, is an integral part of the assistance as shortage of such trained professionals would be a serious obstacle to

IAEA Syllabus for the Education and Training of Radiation Oncologists. Endorsed by the American Society for Radiation Oncology (ASTRO) and the European Society for Therapeutic Radiology and Oncology (ESTRO) (Russian Edition)

International Nuclear Information System (INIS)

2014-01-01

Cancer is one of the leading causes of death globally and cancer incidence is predicted to increase, especially in developing countries. Almost 13% of all deaths worldwide are caused by cancer. In 2005, there were more than 7.6 million cancer deaths worldwide and 10 million newly diagnosed cases of cancer. Today there are more new cancer cases every year in lowmiddle income (LMI) countries than in industrialized countries, and cancer rates are projected to increase significantly in developing countries. By 2020, two-thirds of the projected 10 million annual cancer deaths will be in developing countries. Radiotherapy plays a fundamental role in the continuum of cancer care. However, this technology is not comprehensively provided and in some countries not provided at all. According to the IAEA's Directory of Radiotherapy Centers (DIRAC), as of January 2004 there were about 2000 radiotherapy centres in the developing world with fewer than 2500 teletherapy machines dedicated to cancer therapy. The deficit is not just one of machines - each radiotherapy facility needs trained staff (radiation oncologists, medical physicists, technologists, radiation oncology nurses and maintenance engineers) as well as appropriate arrangements for radiation protection, safety, security and a continuing and ongoing effort to ensure the quality of the radiotherapy process. Strengthening the capability of ministries of health and other health sector institutions for assessing options, formulating policies, and setting priorities is also crucial. The International Atomic Energy Agency (IAEA) has been assisting its Member States in the establishment, operation and upgrading of radiation oncology facilities for many years. Human resource development, which includes training of radiation oncologists, medical physicists, radiation therapy technologists and radiation oncology nurses, is an integral part of the assistance as shortage of such trained professionals would be a serious obstacle to

IAEA Syllabus for the Education and Training of Radiation Oncologists. Endorsed by the American Society for Radiation Oncology (ASTRO) and the European Society for Therapeutic Radiology and Oncology (ESTRO) (Arabic Edition)

International Nuclear Information System (INIS)

2014-01-01

Cancer is one of the leading causes of death globally and cancer incidence is predicted to increase, especially in developing countries. Almost 13% of all deaths worldwide are caused by cancer. In 2005, there were more than 7.6 million cancer deaths worldwide and 10 million newly diagnosed cases of cancer. Today there are more new cancer cases every year in lowmiddle income (LMI) countries than in industrialized countries, and cancer rates are projected to increase significantly in developing countries. By 2020, two-thirds of the projected 10 million annual cancer deaths will be in developing countries. Radiotherapy plays a fundamental role in the continuum of cancer care. However, this technology is not comprehensively provided and in some countries not provided at all. According to the IAEA's Directory of Radiotherapy Centers (DIRAC), as of January 2004 there were about 2000 radiotherapy centres in the developing world with fewer than 2500 teletherapy machines dedicated to cancer therapy. The deficit is not just one of machines - each radiotherapy facility needs trained staff (radiation oncologists, medical physicists, technologists, radiation oncology nurses and maintenance engineers) as well as appropriate arrangements for radiation protection, safety, security and a continuing and ongoing effort to ensure the quality of the radiotherapy process. Strengthening the capability of ministries of health and other health sector institutions for assessing options, formulating policies, and setting priorities is also crucial. The International Atomic Energy Agency (IAEA) has been assisting its Member States in the establishment, operation and upgrading of radiation oncology facilities for many years. Human resource development, which includes training of radiation oncologists, medical physicists, radiation therapy technologists and radiation oncology nurses, is an integral part of the assistance as shortage of such trained professionals would be a serious obstacle to

Downregulation of B-myb promotes senescence via the ROS-mediated p53/p21 pathway, in vascular endothelial cells.

Science.gov (United States)

Zhou, Zhihui; Yin, Yanlin; Chang, Qun; Sun, Guanqun; Lin, Jiahui; Dai, Yalei

2017-04-01

To reveal whether B-myb is involved in preventing senescence of vascular endothelial cells, and if so, to identify possible mechanisms for it. C57/BL6 male mice and primary human aortic endothelial cells (HAECs) were used. Bleomycin was applied to induce stress-related premature senescence. B-myb knockdown was achieved using an siRNA technique and cell senescence was assessed using the senescence-associated β-galactosidase (SA-β-gal) assay. Intracellular reactive oxygen species (ROS) production was analysed using an ROS assay kit and cell proliferation was evaluated using KFluor488 EdU kit. Capillary tube network formation was determined by Matrigel assay. Expressions of mRNA and protein levels were detected by real-time PCR and western blotting. B-myb expression significantly decreased, while p53 and p21 expressions increased in the aortas of aged mice. This expression pattern was also found in replicative senescent HAECs and senescent HAECs induced by bleomycin. B-myb knockdown resulted in upregulation of p22 phox , ROS accumulation and cell senescence of HAECs. Downregulation of B-myb significantly inhibited cell proliferation and capillary tube network formation and activated the p53/p21 signalling pathway. Blocking ROS production or inhibiting p53 activation remarkably attenuated SA-β-gal activity and delayed cell senescence induced by B-myb-silencing. Downregulation of B-myb induced senescence by upregulation of p22 phox and activation of the ROS/p53/p21 pathway, in our vascular endothelial cells, suggesting that B-myb may be a novel candidate for regulating cell senescence to protect against endothelial senescence-related cardiovascular diseases. © 2016 John Wiley & Sons Ltd.

Mtf-1 lymphoma-susceptibility locus affects retention of large thymocytes with high ROS levels in mice after γ-irradiation

International Nuclear Information System (INIS)

Maruyama, Masaki; Yamamoto, Takashi; Kohara, Yuki; Katsuragi, Yoshinori; Mishima, Yukio; Aoyagi, Yutaka; Kominami, Ryo

2007-01-01

Mouse strains exhibit different susceptibilities to γ-ray-induced thymic lymphomas. Our previous study identified Mtf-1 (metal responsive transcription factor-1) as a candidate susceptibility gene, which is involved in the radiation-induced signaling pathway that regulates the cellular reactive oxygen species (ROS). To reveal the mechanism for the increased susceptibility conferred by Mtf-1 locus, we examined early effects of γ-ray on ROS levels in vivo and its difference between Mtf-1 susceptible and resistant congenic mice. Here, we show the detection of clonally growing thymocytes at 4 weeks after irradiation, indicating the start of clonal expansion at a very early stage. We also show that large thymocytes with higher ROS levels and a proliferation capacity were more numerous in the Mtf-1 susceptible mice than the resistant mice when examined at 7 days after irradiation, although such tendency was not found in mice lacking one allele of Bcl11b tumor suppressor gene. This high retention of the large thymocytes, at a high risk for ROS-induced mutation, is a compensatory proliferation and regeneration response to depletion of the thymocytes after irradiation and the response is likely to augment the development of prelymphoma cells leading to thymic lymphomas

Tyrosine kinase receptor c-ros-oncogene 1 inhibition alleviates aberrant bone formation of TWIST-1 haploinsufficient calvarial cells from Saethre-Chotzen syndrome patients.

Science.gov (United States)

Camp, Esther; Anderson, Peter J; Zannettino, Andrew C W; Glackin, Carlotta A; Gronthos, Stan

2018-09-01

Saethre-Chotzen syndrome (SCS), associated with TWIST-1 mutations, is characterized by premature fusion of cranial sutures. TWIST-1 haploinsufficiency, leads to alterations in suture mesenchyme cellular gene expression patterns, resulting in aberrant osteogenesis and craniosynostosis. We analyzed the expression of the TWIST-1 target, Tyrosine kinase receptor c-ros-oncogene 1 (C-ROS-1) in TWIST-1 haploinsufficient calvarial cells derived from SCS patients and calvaria of Twist-1 del/+ mutant mice and found it to be highly expressed when compared to TWIST-1 wild-type controls. Knock-down of C-ROS-1 expression in TWIST-1 haploinsufficient calvarial cells derived from SCS patients was associated with decreased capacity for osteogenic differentiation in vitro. Furthermore, treatment of human SCS calvarial cells with the tyrosine kinase chemical inhibitor, Crizotinib, resulted in reduced C-ROS-1 activity and the osteogenic potential of human SCS calvarial cells with minor effects on cell viability or proliferation. Cultured human SCS calvarial cells treated with Crizotinib exhibited a dose-dependent decrease in alkaline phosphatase activity and mineral deposition, with an associated decrease in expression levels of Runt-related transcription factor 2 and OSTEOPONTIN, with reduced PI3K/Akt signalling in vitro. Furthermore, Crizotinib treatment resulted in reduced BMP-2 mediated bone formation potential of whole Twist-1 del/+ mutant mouse calvaria organotypic cultures. Collectively, these results suggest that C-ROS-1 promotes osteogenic differentiation of TWIST-1 haploinsufficient calvarial osteogenic progenitor cells. Furthermore, the aberrant osteogenic potential of these cells is inhibited by the reduction of C-ROS-1. Therefore, targeting C-ROS-1 with a pharmacological agent, such as Crizotinib, may serve as a novel therapeutic strategy to alleviate craniosynostosis associated with aberrant TWIST-1 function. © 2018 Wiley Periodicals, Inc.

Escherichia coli LF82 differentially regulates ROS production and mucin expression in intestinal epithelial T84 cells: implication of NOX1.

Science.gov (United States)

Elatrech, Imen; Marzaioli, Viviana; Boukemara, Hanane; Bournier, Odile; Neut, Christel; Darfeuille-Michaud, Arlette; Luis, José; Dubuquoy, Laurent; El-Benna, Jamel; My-Chan Dang, Pham; Marie, Jean-Claude

2015-05-01

Increased reactive oxygen species (ROS) production is associated with inflamed ileal lesions in Crohn's disease colonized by pathogenic adherent-invasive Escherichia coli LF82. We investigated whether such ileal bacteria can modulate ROS production by epithelial cells, thus impacting on inflammation and mucin expression. Ileal bacteria from patients with Crohn's disease were incubated with cultured epithelial T84 cells, and ROS production was assayed using the luminol-amplified chemiluminescence method. The gentamicin protection assay was used for bacterial invasion of T84 cell. The expression of NADPH oxidase (NOX) subunits, mucin, and IL-8 was analyzed by quantitative real-time PCR and Western blots. Involvement of NOX and ROS was analyzed using diphenyleneiodonium (DPI) and N-acetylcysteine (NAC). Among different bacteria tested, only LF82 induced an increase of ROS production by T84 cells in a dose-dependent manner. This response was inhibited by DPI and NAC. Heat- or ethanol-attenuated LF82 bacteria and the mutant LF82ΔFimA, which does not express pili type 1 and poorly adheres to epithelial cells, did not induce the oxidative response. The LF82-induced oxidative response coincides with its invasion in T84 cells, and both processes were inhibited by DPI. Also, we observed an increased expression of NOX1 and NOXO1 in response to LF82 bacteria versus the mutant LF82ΔFimA. Furthermore, LF82 inhibited mucin gene expression (MUC2 and MUC5AC) in T84 cells while increasing the chemotactic IL-8 expression, both in a DPI-sensitive manner. Adherent-invasive E. coli LF82 induced ROS production by intestinal NADPH oxidase and altered mucin and IL-8 expression, leading to perpetuation of inflammatory lesions in Crohn's disease.

Rosé Wine Fining Using Polyvinylpolypyrrolidone: Colorimetry, Targeted Polyphenomics, and Molecular Dynamics Simulations.

Science.gov (United States)

Gil, Mélodie; Avila-Salas, Fabian; Santos, Leonardo S; Iturmendi, Nerea; Moine, Virginie; Cheynier, Véronique; Saucier, Cédric

2017-12-06

Polyvinylpolypyrrolidone (PVPP) is a fining agent polymer used in winemaking to adjust rosé wine color and to prevent organoleptic degradations by reducing polyphenol content. The impact of this polymer on color parameters and polyphenols of rosé wines was investigated, and the binding specificity of polyphenols toward PVPP was determined. Color measured by colorimetry decreased after treatment, thus confirming the adsorption of anthocyanins and other pigments. Phenolic composition was determined before and after fining by targeted polyphenomics (Ultra Performance Liquid Chromatography (UPLC)-Electrospray Ionization(ESI)-Mass Spectrometry (MS/MS)). MS analysis showed adsorption differences among polyphenol families. Flavonols (42%) and flavanols (64%) were the most affected. Anthocyanins were not strongly adsorbed on average (12%), but a specific adsorption of coumaroylated anthocyanins was observed (37%). Intermolecular interactions were also studied using molecular dynamics simulations. Relative adsorptions of flavanols were correlated with the calculated interaction energies. The specific affinity of coumaroylated anthocyanins toward PVPP was also well explained by the molecular modeling.

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