Causes of death of patients with lung cancer.

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Nichols, Larry; Saunders, Rachel; Knollmann, Friedrich D

2012-12-01

The causes of death for patients with lung cancer are inadequately described. To categorize the immediate and contributing causes of death for patients with lung cancer. The autopsies from 100 patients who died of lung cancer between 1990 and February 2011 were analyzed. Tumor burden was judged the immediate cause of death in 30 cases, including 26 cases of extensive metastases and 4 cases with wholly or primarily lung tumor burden (causing respiratory failure). Infection was the immediate cause of death for 20 patients, including 8 with sepsis and 12 with pneumonia. Complications of metastatic disease were the immediate causes of death in 18 cases, including 6 cases of hemopericardium from pericardial metastases, 3 from myocardial metastases, 3 from liver metastases, and 3 from brain metastases. Other immediate causes of death were pulmonary hemorrhage (12 cases), pulmonary embolism (10 cases, 2 tumor emboli), and pulmonary diffuse alveolar damage (7 cases). From a functional (pathophysiologic) perspective, respiratory failure could be regarded as the immediate cause of death (or mechanism of death) in 38 cases, usually because of a combination of lung conditions, including emphysema, airway obstruction, pneumonia, hemorrhage, embolism, resection, and lung injury in addition to the tumor. For 94 of the 100 patients, there were contributing causes of death, with an average of 2.5 contributing causes and up to 6 contributing causes of death. The numerous and complex ways lung cancer kills patients pose a challenge for efforts to extend and improve their lives.

Changes in siblings after the death of a child from cancer.

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Foster, Terrah L; Gilmer, Mary Jo; Vannatta, Kathryn; Barrera, Maru; Davies, Betty; Dietrich, Mary S; Fairclough, Diane L; Gerhardt, Cynthia A

2012-01-01

Few studies have examined changes in siblings after the death of a brother or sister, particularly from mother, father, and sibling perspectives within the first year after death. This descriptive study identified and assessed the frequency of changes in siblings after a child's death from cancer. Participants were recruited from cancer registries at 3 hospitals in the United States and Canada 3 to 12 months after the child's death. Thirty-six mothers, 24 fathers, and 39 siblings from 40 families were included. Semistructured interviews using open-ended questions were conducted with each parent and sibling separately in the home. Content analysis identified emerging themes, and the McNemar tests compared frequencies between each paired set of reports (sibling vs mother, sibling vs father, mother vs father). Sixty-nine percent of participants reported personal changes in siblings (eg, changes in personality, school work, goals/life perspective, activities/interests). Forty-seven percent noted changes in siblings' relationships with family members and peers. Only 21% of participants reported no changes attributed to the death. Comparisons of frequencies across informants were not significant. Most siblings experienced changes in multiple areas of their lives after the death of a brother or sister to cancer. Some changes reflected siblings that were positively adapting to the death, whereas other changes reflected difficulties. Our findings offer guidance to improve aftercare for bereaved siblings and their families. Additional research is needed to further delineate the needs of bereaved siblings and to develop strategies to promote adaptation to loss.

Nerve Growth Factor in Cancer Cell Death and Survival

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Molloy, Niamh H.; Read, Danielle E.; Gorman, Adrienne M.

2011-01-01

One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75 NTR , a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75 NTR . For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75 NTR . This latter signaling through p75 NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75 NTR mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer

Association of sense of coherence and supernatural beliefs with death anxiety and death depression among Romanian cancer patients.

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Postolică, Roxana; Enea, Violeta; Dafinoiu, Ion; Petrov, Iuliana; Azoicăi, Doina

2018-02-02

The aim of this cross-sectional study was to examine the association of supernatural beliefs and sense of coherence with death anxiety and death depression in a Romanian sample of cancer patients. We found support for the terror management theory worldview defence hypothesis postulating the presence of a curvilinear relation between death anxiety and supernatural beliefs among cancer patients. Results conformed to an inverted U-shape quadratic regression, indicating that cancer patients who scored moderately on supernatural beliefs were afraid of death the most, while death anxiety was lowest for the extreme atheists and extreme believers in supernatural entities.

Public reaction to the death of Steve Jobs: implications for cancer communication.

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Myrick, Jessica Gall; Noar, Seth M; Willoughby, Jessica Fitts; Brown, Jennifer

2014-01-01

The present study aimed to examine the public reaction to the death of Steve Jobs, focusing on general and cancer-specific information seeking and interpersonal communication. Shortly after Jobs's death, employees from a large university in the Southeastern United States (N = 1,398) completed a web-based survey. Every employee had heard about Steve Jobs's death, and 97% correctly identified pancreatic cancer as the cause of his death. General (50%) and pancreatic cancer-specific (7%) information seeking, as well as general (74%) and pancreatic cancer-specific (17%) interpersonal communication, took place in response to Steve Jobs's death. In multivariate logistic regression analyses controlling for demographics and several cancer-oriented variables, both identification with Steve Jobs and cancer worry in response to Steve Jobs's death significantly (p < .05) predicted pancreatic cancer information seeking as well as interpersonal communication about pancreatic cancer. Additional analyses revealed that cancer worry partially mediated the effects of identification on these outcome variables. Implications of these results for future research as well as cancer prevention and communication efforts are discussed.

Nerve Growth Factor in Cancer Cell Death and Survival

Energy Technology Data Exchange (ETDEWEB)

Molloy, Niamh H.; Read, Danielle E.; Gorman, Adrienne M., E-mail: adrienne.gorman@nuigalway.ie [Apoptosis Research Centre, School of Natural Sciences, National University of Ireland, Galway (Ireland)

2011-02-01

One of the major challenges for cancer therapeutics is the resistance of many tumor cells to induction of cell death due to pro-survival signaling in the cancer cells. Here we review the growing literature which shows that neurotrophins contribute to pro-survival signaling in many different types of cancer. In particular, nerve growth factor, the archetypal neurotrophin, has been shown to play a role in tumorigenesis over the past decade. Nerve growth factor mediates its effects through its two cognate receptors, TrkA, a receptor tyrosine kinase and p75{sup NTR}, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75{sup NTR}. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75{sup NTR}. This latter signaling through p75{sup NTR} promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75{sup NTR} mediates cell death and prevents metastasis. In prostate cancer, expression of this receptor is lost, which contributes to tumor progression by allowing cells to survive, proliferate and metastasize. This review focuses on our current knowledge of neurotrophin signaling in cancer, with a particular emphasis on nerve growth factor regulation of cell death and survival in cancer.

Observed and Predicted Risk of Breast Cancer Death in Randomized Trials on Breast Cancer Screening.

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Autier, Philippe; Boniol, Mathieu; Smans, Michel; Sullivan, Richard; Boyle, Peter

2016-01-01

The role of breast screening in breast cancer mortality declines is debated. Screening impacts cancer mortality through decreasing the number of advanced cancers with poor diagnosis, while cancer treatment works through decreasing the case-fatality rate. Hence, reductions in cancer death rates thanks to screening should directly reflect reductions in advanced cancer rates. We verified whether in breast screening trials, the observed reductions in the risk of breast cancer death could be predicted from reductions of advanced breast cancer rates. The Greater New York Health Insurance Plan trial (HIP) is the only breast screening trial that reported stage-specific cancer fatality for the screening and for the control group separately. The Swedish Two-County trial (TCT)) reported size-specific fatalities for cancer patients in both screening and control groups. We computed predicted numbers of breast cancer deaths, from which we calculated predicted relative risks (RR) and (95% confidence intervals). The Age trial in England performed its own calculations of predicted relative risk. The observed and predicted RR of breast cancer death were 0.72 (0.56-0.94) and 0.98 (0.77-1.24) in the HIP trial, and 0.79 (0.78-1.01) and 0.90 (0.80-1.01) in the Age trial. In the TCT, the observed RR was 0.73 (0.62-0.87), while the predicted RR was 0.89 (0.75-1.05) if overdiagnosis was assumed to be negligible and 0.83 (0.70-0.97) if extra cancers were excluded. In breast screening trials, factors other than screening have contributed to reductions in the risk of breast cancer death most probably by reducing the fatality of advanced cancers in screening groups. These factors were the better management of breast cancer patients and the underreporting of breast cancer as the underlying cause of death. Breast screening trials should publish stage-specific fatalities observed in each group.

Trends in compensation for deaths from occupational cancer in Canada: a descriptive study.

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Del Bianco, Ann; Demers, Paul A

2013-09-01

Occupational cancer is the leading cause of work-related deaths, yet it is often unrecognized and under reported, and associated claims for compensation go unfiled. We sought to examine trends in deaths from occupational cancer, high-risk industries and exposures, and commonly compensated categories of occupational cancers. In addition, we compared deaths from occupational lung cancer for which compensation had been given with total deaths from lung cancer. We used data from the Association of Workers' Compensation Boards of Canada pertaining to the nature and source of the injury or disease and the industry in which it occurred (by jurisdiction) to describe trends in compensated claims for deaths from occupational cancer in Canada for the period 1997-2010. We used data published by the Canadian Cancer Society in Canadian Cancer Statistics to compare compensated occupational lung cancer deaths with total estimated lung cancer deaths for the period between 2006 and 2010. Compensated claims for deaths from occupational cancer have increased in recent years and surpassed those for traumatic injuries and disorders in Canada, particularly in Ontario. Between 1997 and 2010, one-half of all compensated deaths from occupational cancer in Canada were from Ontario. High-risk industries for occupational cancer include manufacturing, construction, mining and, more recently, government services. Deaths from lung cancer and mesothelioma comprise most of the compensated claims for deaths from occupational cancer in Ontario and Canada. These diseases are usually the result of asbestos exposure. The burden of other occupational carcinogens is not reflected in claims data. Although the number of accepted claims for deaths from occupational cancers has increased in recent years, these claims likely only represent a fraction of the true burden of this problem. Increased education of patients, workers at high risk of exposure and health care providers is needed to ensure that people

QuickStats: Age-Adjusted Death Rates* for Top Five Causes of Cancer Death,(†) by Race/Hispanic Ethnicity - United States, 2014.

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2016-09-16

In 2014, the top five causes of cancer deaths for the total population were lung, colorectal, female breast, pancreatic, and prostate cancer. The non-Hispanic black population had the highest age-adjusted death rates for each of these five cancers, followed by non-Hispanic white and Hispanic groups. The age-adjusted death rate for lung cancer, the leading cause of cancer death in all groups, was 42.1 per 100,000 standard population for the total population, 45.4 for non-Hispanic white, 45.7 for non-Hispanic black, and 18.3 for Hispanic populations.

Cytotoxic macrophage-released tumour necrosis factor-alpha (TNF-α) as a killing mechanism for cancer cell death after cold plasma activation

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Kaushik, Nagendra Kumar; Kaushik, Neha; Min, Booki; Choi, Ki Hong; Hong, Young June; Miller, Vandana; Fridman, Alexander; Choi, Eun Ha

2016-03-01

The present study aims at studying the anticancer role of cold plasma-activated immune cells. The direct anti-cancer activity of plasma-activated immune cells against human solid cancers has not been described so far. Hence, we assessed the effect of plasma-treated RAW264.7 macrophages on cancer cell growth after co-culture. In particular, flow cytometer analysis revealed that plasma did not induce any cell death in RAW264.7 macrophages. Interestingly, immunofluorescence and western blot analysis confirmed that TNF-α released from plasma-activated macrophages acts as a tumour cell death inducer. In support of these findings, activated macrophages down-regulated the cell growth in solid cancer cell lines and induced cell death in vitro. Together our findings suggest plasma-induced reactive species recruit cytotoxic macrophages to release TNF-α, which blocks cancer cell growth and can have the potential to contribute to reducing tumour growth in vivo in the near future.

Cytotoxic macrophage-released tumour necrosis factor-alpha (TNF-α) as a killing mechanism for cancer cell death after cold plasma activation

International Nuclear Information System (INIS)

Kaushik, Nagendra Kumar; Kaushik, Neha; Min, Booki; Choi, Ki Hong; Hong, Young June; Choi, Eun Ha; Miller, Vandana; Fridman, Alexander

2016-01-01

The present study aims at studying the anticancer role of cold plasma-activated immune cells. The direct anti-cancer activity of plasma-activated immune cells against human solid cancers has not been described so far. Hence, we assessed the effect of plasma-treated RAW264.7 macrophages on cancer cell growth after co-culture. In particular, flow cytometer analysis revealed that plasma did not induce any cell death in RAW264.7 macrophages. Interestingly, immunofluorescence and western blot analysis confirmed that TNF-α released from plasma-activated macrophages acts as a tumour cell death inducer. In support of these findings, activated macrophages down-regulated the cell growth in solid cancer cell lines and induced cell death in vitro. Together our findings suggest plasma-induced reactive species recruit cytotoxic macrophages to release TNF-α, which blocks cancer cell growth and can have the potential to contribute to reducing tumour growth in vivo in the near future. (paper)

Chronological shifts and changing causes of death after radiotherapy for early-stage oral cancer.

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Fujisawa, Rina; Shibuya, Hitoshi; Harata, Naoki; Yuasa-Nakagawa, Keiko; Toda, Kazuma; Hayashi, Keiji

2014-02-01

Following recent improvements in the curability of oral cancer, chronological shifts and changes in the causes of death after treatment have been observed. We conducted a review of the post-treatment causes of death following radiotherapy for oral cancers. The medical records of 966 patients with early-stage (stage I and II) oral cancer treated at our institute between 1980 and 2001 were reviewed, and the chronological shifts and changes in the causes of death after radiotherapy were assessed. Of the 966 patients enrolled in this study, 365 have died to date. Two hundred and eleven patients died of their primary malignancy; 193 of these deaths occurred within 5 years of treatment for the primary oral cancer. The second most frequent cause of death was second primary cancer (n = 90). Twenty-three patients with head and neck cancers and 18 patients with esophageal cancers died within 10 years of radiotherapy, and six patients with lung cancers died after more than 10 years. Within the first 5 years following treatment, the major cause of death was the primary oral cancer. After 5-10 years, a second primary cancer, such as head and neck cancer or esophageal cancer, became the leading cause of death. Over a 10-year period, the proportion of deaths from a second primary cancer in the lung was significant. We have demonstrated that there are chronological shifts and changes in the causes of death following treatment for early-stage oral cancer.

Classification of Cancer-related Death Certificates using Machine Learning

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Luke Butt

2013-05-01

Full Text Available BackgroundCancer monitoring and prevention relies on the critical aspect of timely notification of cancer cases. However, the abstraction and classification of cancer from the free-text of pathology reports and other relevant documents, such as death certificates, exist as complex and time-consuming activities.AimsIn this paper, approaches for the automatic detection of notifiable cancer cases as the cause of death from free-text death certificates supplied to Cancer Registries are investigated.Method A number of machine learning classifiers were studied. Features were extracted using natural language techniques and the Medtex toolkit. The numerous features encompassed stemmed words, bi-grams, and concepts from the SNOMED CT medical terminology. The baseline consisted of a keyword spotter using keywords extracted from the long description of ICD-10 cancer related codes.ResultsDeath certificates with notifiable cancer listed as the cause of death can be effectively identified with the methods studied in this paper. A Support Vector Machine (SVM classifier achieved best performance with an overall F-measure of 0.9866 when evaluated on a set of 5,000 free-text death certificates using the token stem feature set. The SNOMED CT concept plus token stem feature set reached the lowest variance (0.0032 and false negative rate (0.0297 while achieving an F-measure of 0.9864. The SVM classifier accounts for the first 18 of the top 40 evaluated runs, and entails the most robust classifier with a variance of 0.001141, half the variance of the other classifiers.ConclusionThe selection of features significantly produced the most influences on the performance of the classifiers, although the type of classifier employed also affects performance. In contrast, the feature weighting schema created a negligible effect on performance. Specifically, it is found that stemmed tokens with or without SNOMED CT concepts create the most effective feature when combined with

Count Data On Cancer Death In Ohio A Bayesian Analysis

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Walaa Hamdi

2015-08-01

Full Text Available This paper considers statistical modeling of count data on cancer death in Ohio State. We obtained count data on male and female from a website of the Centers for Disease Control and Prevention and used Bayesian analyses to find suitable models which help us to do inferences and predictions for next year. To assist us in selecting appropriate models we use criteria such as the DIC. In this paper we analyze the data to spatial longitudinal so we can capture possible correlations. Using our analyses we make predictions of the numbers of people who will die with cancer in a future year in Ohio State.

Clinical presentation and in-hospital death in acute pulmonary embolism: does cancer matter?

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Casazza, Franco; Becattini, Cecilia; Rulli, Eliana; Pacchetti, Ilaria; Floriani, Irene; Biancardi, Marco; Scardovi, Angela Beatrice; Enea, Iolanda; Bongarzoni, Amedeo; Pignataro, Luigi; Agnelli, Giancarlo

2016-09-01

Cancer is one of the most common risk factors for acute pulmonary embolism (PE), but only few studies report on the short-term outcome of patients with PE and a history of cancer. The aim of the study was to assess whether a cancer diagnosis affects the clinical presentation and short-term outcome in patients hospitalized for PE who were included in the Italian Pulmonary Embolism Registry. All-cause and PE-related in-hospital deaths were also analyzed. Out of 1702 patients, 451 (26.5 %) of patients had a diagnosis of cancer: cancer was known at presentation in 365, or diagnosed during the hospital stay for PE in 86 (19 % of cancer patients). Patients with and without cancer were similar concerning clinical status at presentation. Patients with cancer less commonly received thrombolytic therapy, and more often had an inferior vena cava filter inserted. Major or intracranial bleeding was not different between groups. In-hospital all-cause death occurred in 8.4 and 5.9 % of patients with and without cancer, respectively. At multivariate analysis, cancer (OR 2.24, 95 % CI 1.27-3.98; P = 0.006) was an independent predictor of in-hospital death. Clinical instability, PE recurrence, age ≥75 years, recent bed rest ≥3 days, but not cancer, were independent predictors of in-hospital death due to PE. Cancer seems a weaker predictor of all-cause in-hospital death compared to other factors; the mere presence of cancer, without other risk factors, leads to a probability of early death of 2 %. In patients with acute PE, cancer increases the probability of in-hospital all-cause death, but does not seem to affect the clinical presentation or the risk of in-hospital PE-related death.

Validation and application of a death proxy in adult cancer patients.

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Mealing, Nicole M; Dobbins, Timothy A; Pearson, Sallie-Anne

2012-07-01

PURPOSE: Fact of death is not always available on data sets used for pharmacoepidemiological research. Proxies may be an appropriate substitute in the absence of death data. The purposes of this study were to validate a proxy for death in adult cancer patients and to assess its performance when estimating survival in two cohorts of cancer patients. METHODS: We evaluated 30-, 60-, 90- and 180-day proxies overall and by cancer type using data from 12 394 Australian veterans with lung, colorectal, breast or prostate cancer. The proxy indicated death if the difference between the last dispensing record and the end of the observational period exceeded the proxy cutoff. We then compared actual survival to 90-day proxy estimates in a subset of 4090 veterans with 'full entitlements' for pharmaceutical items and in 3704 Australian women receiving trastuzumab for HER2+ metastatic breast cancer. RESULTS: The 90-day proxy was optimal with an overall sensitivity of 99.3% (95%CI: 98.4-99.7) and a specificity of 97.6% (95%CI: 91.8-99.4). These measures remained high when evaluated by cancer type and spread of disease. The application of the proxy using the most conservative date of death estimate (date of last dispensing) generally underestimated survival, with estimates up to 3 months shorter than survival based on fact of death. CONCLUSIONS: A 90-day death proxy is a robust substitute to identify death in a chronic population when fact of death is not available. The proxy is likely to be valid across a range of chronic diseases as it relies on the presence of 'regular' dispensing records for individual patients. Copyright © 2011 John Wiley & Sons, Ltd. Copyright © 2011 John Wiley & Sons, Ltd.

Measuring death-related anxiety in advanced cancer: preliminary psychometrics of the Death and Dying Distress Scale.

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Lo, Christopher; Hales, Sarah; Zimmermann, Camilla; Gagliese, Lucia; Rydall, Anne; Rodin, Gary

2011-10-01

The alleviation of distress associated with death and dying is a central goal of palliative care, despite the lack of routine measurement of this outcome. In this study, we introduce the Death and Dying Distress Scale (DADDS), a new, brief measure we have developed to assess death-related anxiety in advanced cancer and other palliative populations. We describe its preliminary psychometrics based on a sample of 33 patients with advanced or metastatic cancer. The DADDS broadly captures distress about the loss of time and opportunity, the process of death and dying, and its impact on others. The initial version of the scale has a one-factor structure and good internal reliability. Dying and death-related distress was positively associated with depression and negatively associated with spiritual, emotional, physical, and functional well-being, providing early evidence of construct validity. This distress was relatively common, with 45% of the sample scoring in the upper reaches of the scale, suggesting that the DADDS may be a relevant outcome for palliative intervention. We conclude by presenting a revised 15-item version of the scale for further study in advanced cancer and other palliative populations.

Cause and place of death in patients dying with colorectal cancer.

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Jones, O M; John, S K P; Horseman, N; Lawrance, R J; Fozard, J B J

2007-03-01

Few studies on colorectal cancer look at the one-third of patients for whom treatment fails and who need a management strategy for death. This paper has examined the mode and place of death in patients with colorectal cancer. This study was a review of 209 deaths, analysed between January 2001 and September 2004 by retrospective review of a prospectively collected database. A total of 118 patients (group 1) had undergone resection of their primary colorectal cancer, 20 (group 2) had had a defunctioning stoma or bypass surgery and the remaining 71 patients (group 3) had either had no surgery, an open and close laparotomy or had a colonic stent. One hundred and fifty-six (75%) patients died of colorectal cancer with the remainder dying of other causes. The number of admissions to hospital and the number of days spent in hospital from diagnosis to death were greatest in group 1. Overall, only 34 patients (22%) dying from colorectal cancer died at home. Forty (26%) died in hospital and 70 (45%) died in a palliative care unit. Patients dying from colorectal cancer who undergo surgical resection of their primary tumour spend more time between diagnosis and death in hospital. They are also more likely to die in hospital than patients treated by surgical palliation or nonsurgically. Patients who are treated palliatively from the outset (group 3) are most likely to die at home. If hospital is accepted as an appropriate place for death from colorectal cancer, then greater provision for this should be made.

Estimates of cancer deaths attributable to behavioural risk factors in Italy, 2013.

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Battisti, Francesca; Carreras, Giulia; Grassi, Tommaso; Chellini, Elisabetta; Gorini, Giuseppe

2017-01-01

"Non-communicable diseases cause more than 80% of deaths in europe and, among these, 20% are caused by cancer. Modifiable lifestyle factors considered in the italian national programme "Guadagnare salute" (Gaining health), such as tobacco smoking, unhealthy diet, physical inactivity, overweight, and excessive alcohol use, are amongst the major causes of cancer deaths. The aims of this study was to estimate the number of deaths attributable to lifestyle factors for italy and for italian regions in 2013 and to describe its variation in relation to the regional prevalence of risk factors exposure. For Italy and for each italian region, deaths attributable to lifestyle factors were estimated using the methodology of the Global Burden of disease (GBd) study. italian mortality data of 2013 and risks attributable to these lifestyle factors for each cancer site for italy from the GBd study were used. Prevalence of exposure to lifestyles in Italy and in each Italian Region was collected for the period 2008-2013. In 2013, at least 66,605 cancer deaths in italy were attributable to lifestyle factors, accounting for 37.9% of all cancer deaths: 34.1% of cancer deaths in men and 9.0% in women were attributable to smoking; in men and women, respectively, 3.3% and 2.8% were attributable to excessive alcohol consumption; 5.3 % and 6.7% to overweight; 10.1% and 7.1% to dietary risk factors; 1.9% and 4.2% to physical inactivity. A moderate variability of percentage of deaths attributable to modifi able lifestyle factors by region was also detected due to different prevalence values of exposure to lifestyles occurred in last decades. At least 45,000 cancer deaths in men and 21,000 in women occurred in 2013 were attributable to modifi able risk factors, whose prevalence varied by region and which could be averted through the implementation of primary prevention interventions."

Association between unilateral or bilateral mastectomy and breast cancer death in patients with unilateral ductal carcinoma.

Science.gov (United States)

Agarwal, Shailesh; Pappas, Lisa; Agarwal, Jayant

2017-01-01

Utilization of bilateral mastectomy for unilateral breast cancer is increasing despite cost and surgical risks with conflicting reports of survival benefit. Current studies evaluating death after bilateral mastectomy have included patients treated both with breast conservation therapy and unilateral mastectomy. In this study, we directly compared breast cancer-specific death of patients who underwent bilateral or unilateral mastectomy for unilateral breast cancer using a matched cohort analysis. This was an observational study of women diagnosed with unilateral breast cancer from 1998 through 2002, using the Surveillance, Epidemiology, and End Results (SEER) database. A 4-to-1 matched cohort of patients was selected including 14,075 patients. Mortality of the groups was compared using Cox proportional hazards models for cause-specific death. A total of 41,510 patients diagnosed with unilateral breast cancer were included. Unilateral mastectomy was performed in 93% of patients, while bilateral mastectomy was performed in the remaining 7% of patients. When 4-to-1 matching was performed, 11,260 unilateral mastectomy and 2,815 bilateral mastectomy patients were included. Patients with bilateral mastectomy did not have a significantly lower hazard of breast cancer-specific death when compared with patients with unilateral mastectomy (hazard ratio: 0.92 vs 1.00, p =0.11). Bilateral mastectomy did not provide a clinically or statistically significant breast cancer-specific mortality benefit over unilateral mastectomy based on a matched cohort analysis of a nationwide population database. These findings should be interpreted in the context of patient preference and alternative benefits of bilateral mastectomy.

Causes of death in long-term survivors of head and neck cancer.

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Baxi, Shrujal S; Pinheiro, Laura C; Patil, Sujata M; Pfister, David G; Oeffinger, Kevin C; Elkin, Elena B

2014-05-15

Survivors of head and neck squamous cell carcinoma (HNSCC) face excess mortality from multiple causes. We used the population-based Surveillance, Epidemiology, and End Results (SEER) cancer registry data to evaluate the causes of death in patients with nonmetastatic HNSCC diagnosed between 1992 and 2005 who survived at least 3 years from diagnosis (long-term survivors). We used competing-risks proportional hazards regression to estimate probabilities of death from causes: HNSCC, second primary malignancy (SPM) excluding HNSCC, cardiovascular disease, and other causes. We identified 35,958 three-year survivors of HNSCC with a median age at diagnosis of 60 years (range = 18-100 years) and a median follow-up of 7.7 years (range = 3-18 years). There were 13,120 deaths during the study period. Death from any cause at 5 and 10 years was 15.4% (95% confidence interval [CI] = 15.0%-15.8%) and 41.0% (95% CI = 40.4%-41.6%), respectively. There were 3852 HNSCC deaths including both primary and subsequent head and neck tumors. The risk of death from HNSCC was greater in patients with nasopharynx or hypopharynx cancer and in patients with locally advanced disease. SPM was the leading cause of non-HNSCC death, and the most common sites of SPM death were lung (53%), esophagus (10%), and colorectal (5%) cancer. Many long-term HNSCC survivors die from cancers other than HNSCC and from noncancer causes. Routine follow-up care for HNSCC survivors should expand beyond surveillance for recurrent and new head and neck cancers. © 2014 American Cancer Society.

Cancer as a cause of death among people with AIDS in the United States

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Simard, Edgar P.; Engels, Eric A.

2010-01-01

Background People with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS), are at increased risk for cancer. Highly active antiretroviral therapy [(HAART), widely available since 1996] has resulted in dramatic declines in AIDS-related deaths. Methods We evaluated cancer as a cause of death in a U.S. registry-based cohort of 83,282 people with AIDS (1980–2006). Causes of death due to AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) were assessed. We evaluated mortality rates and the fraction of deaths due to cancer. Poisson regression assessed rates according to calendar year of AIDS onset. Results Overall mortality declined from 302 (1980–1989), to 140 (1990–1995), to 29 per 1,000 person-years (1996–2006). ADC mortality declined from 2.95 (1980–1989) to 0.65 per 1,000 person-years (1996–2006) (PAIDS-related deaths. Non-Hodgkin lymphoma was the commonest cancer-related cause of death (36% during 1996–2006). Likewise, NADC mortality declined from 2.21 to 0.84 per 1,000 person-years (1980–1989 vs. 1996–2006, PAIDS, cancers account for a growing fraction of deaths. Improved cancer prevention and treatment, particularly for non-Hodgkin lymphoma and lung cancer, would reduce mortality among people with AIDS. PMID:20825305

Effects of a randomized gratitude intervention on death-related fear of recurrence in breast cancer survivors.

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Otto, Amy K; Szczesny, Elana C; Soriano, Emily C; Laurenceau, Jean-Philippe; Siegel, Scott D

2016-12-01

Among the most prevalent and distressing concerns endorsed by breast cancer survivors is fear of cancer recurrence (FOR), and one of the most salient facets is the worry that a recurrence of cancer could cause one's death. The primary goal of the present study was to test the effects of a brief, low-cost gratitude intervention on overall FOR and death-related FOR, positing pursuit of meaningful goals as a theoretically driven putative mediator. To replicate published tests of similar gratitude-eliciting interventions, positive affect (PA) was also considered as an outcome. Sixty-seven women with early stage breast cancer were randomly assigned to either a 6-week online gratitude intervention or a 6-week online control condition. Outcomes were assessed at pre- and posttreatment, as well as 1 month and 3 months after the end of treatment. The mediator, meaningful goal pursuit, was measured via assessments over the 6-week intervention period. Results revealed that patients in the gratitude intervention experienced a significant decrease in death-related FOR compared to the control condition. Moreover, this effect was significantly mediated by meaningful goal pursuit (and not by PA). The gratitude intervention was also found to prevent declines in PA observed in the control condition. Overall, findings support the notion that a brief gratitude intervention can promote well-being and psychological adaptation to cancer by stimulating the pursuit of meaningful goals and subsequently reducing death-related FOR. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

5 CFR 880.207 - Adjustment of accounts after finding of death.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Adjustment of accounts after finding of death. 880.207 Section 880.207 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL... Procedures § 880.207 Adjustment of accounts after finding of death. After a missing annuitant is determined...

Cancer deaths and cases attributable to lifestyle factors and infections in China, 2013.

Science.gov (United States)

Islami, F; Chen, W; Yu, X Q; Lortet-Tieulent, J; Zheng, R; Flanders, W D; Xia, C; Thun, M J; Gapstur, S M; Ezzati, M; Jemal, A

2017-10-01

The burden of cancer in China is high, and it is expected to further increase. Information on cancers attributable to potentially modifiable risk factors is essential in planning preventive measures against cancer. We estimated the number and proportion of cancer deaths and cases attributable to ever-smoking, second-hand smoking, alcohol drinking, low fruit/vegetable intake, excess body weight, physical inactivity, and infections in China, using contemporary data from nationally representative surveys and cancer registries. The number of cancer deaths and cases in 2013 were obtained from the National Central Cancer Registry of China and data on most exposures were obtained from the China National Nutrition and Health Survey 2002 or 2006 and Global Adult Tobacco Smoking 2010. We used a bootstrap simulation method to calculate the number and proportion of cancer deaths and cases attributable to risk factors and their corresponding 95% confidence intervals (CIs), allowing for uncertainty in data. Approximately 718 000 (95% CI 702 100-732 200) cancer deaths in men and 283 100 (278 800-288 800) cancer deaths in women were attributable to the studied risk factors, accounting for 52% of all cancer deaths in men and 35% in women. The numbers for incident cancer cases were 952 500 (95% CI 934 200-971 400) in men and 442 700 (437 200-447 900) in women, accounting for 47% of all incident cases in men and 28% in women. The greatest proportions of cancer deaths attributable to risk factors were for smoking (26%), HBV infection (12%), and low fruit/vegetable intake (7%) in men and HBV infection (7%), low fruit/vegetable intake (6%), and second-hand smoking (5%) in women. Effective public health interventions to eliminate or reduce exposure from these risk factors, notably tobacco control and vaccinations against carcinogenic infections, can have considerable impact on reducing the cancer burden in China. © The Author 2017. Published by Oxford University

CT findings as confirmatory criteria of brain death

International Nuclear Information System (INIS)

Shiogai, Toshiyuki; Takeuchi, Kazuo

1983-01-01

The absence of cerebral circulation and electrocerebral silence have served as an accurate index of irreversible brain death. It is proposed that computed tomography (CT) findings be evaluated as confirmatory criteria of brain death. To this end, CT evaluation of 14 patients satisfying the conventional criteria of brain death was performed. A CT finding of severe compression or dissappearance of the ventricular system, or so called ''brain tamponade'', was seen in 7 (50 %) of the 14 patients. Enhanced contrast CT, especially dynamic CT, usually distinctly reveals the cerebral vessels whenever the cerebral blood flow is preserved; conversely, the lack of enhanced brain structures, even comparing attenuation values, indicates the absence of cerebral blood flow. In 7 (70 %) of 10 patients, however, there was enhanced contrast of vascular brain structures, especially the circle of Willis, major cerebral arteries, choroid plexuses, and venous sinuses. It is suggested that this result is due to the improvement of demonstrability by CT. The usefulness of CT in the confirmation of brain death lies in visualization of the pathological changes associated with a dead brain, such as ''brain tamponade'', and the lack of enhanced contrast indicating the absence of cerebral blood flow. The latter point is still problematic as angiography revealed an extremely low cerebral blood flow in a few cases of ''dead brain'' patients. It is recommended that cerebral blood flow in brain death be evaluated by dynamic CT scanning and correlated with other methods of cerebral blood flow determination (e.g., intravenous digital subtraction angiography). (Author)

CT findings as confirmatory criteria of brain death

Energy Technology Data Exchange (ETDEWEB)

Shiogai, Toshiyuki; Takeuchi, Kazuo (Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine)

1983-12-01

The absence of cerebral circulation and electrocerebral silence have served as an accurate index of irreversible brain death. It is proposed that computed tomography (CT) findings be evaluated as confirmatory criteria of brain death. To this end, CT evaluation of 14 patients satisfying the conventional criteria of brain death was performed. A CT finding of severe compression or dissappearance of the ventricular system, or so called ''brain tamponade'', was seen in 7 (50 %) of the 14 patients. Enhanced contrast CT, especially dynamic CT, usually distinctly reveals the cerebral vessels whenever the cerebral blood flow is preserved; conversely, the lack of enhanced brain structures, even comparing attenuation values, indicates the absence of cerebral blood flow. In 7 (70 %) of 10 patients, however, there was enhanced contrast of vascular brain structures, especially the circle of Willis, major cerebral arteries, choroid plexuses, and venous sinuses. It is suggested that this result is due to the improvement of demonstrability by CT. The usefulness of CT in the confirmation of brain death lies in visualization of the pathological changes associated with a dead brain, such as ''brain tamponade'', and the lack of enhanced contrast indicating the absence of cerebral blood flow. The latter point is still problematic as angiography revealed an extremely low cerebral blood flow in a few cases of ''dead brain'' patients. It is recommended that cerebral blood flow in brain death be evaluated by dynamic CT scanning and correlated with other methods of cerebral blood flow determination (e.g., intravenous digital subtraction angiography).

Preference for place-of-death among terminally ill cancer patients in Denmark

DEFF Research Database (Denmark)

Neergaard, Mette Asbjørn; Jensen, Anders Bonde; Sondergaard, Jens

2011-01-01

Scand J Caring Sci; 2011 Preference for place-of-death among terminally ill cancer patients in Denmark Achieving home death is often seen as an important endpoint in palliative care, but no studies of the preferred place-of-death have yet been conducted in Scandinavia. Furthermore, we do not know...... if professionals' report on deceased patients' preference of place-of-death is a valid information. The aim of this study was to describe where terminally ill Danish cancer patients prefer to die and to determine if their preference changed during the palliative period, as reported retrospectively by bereaved...... GPs and CNs) report retrospectively that most terminally ill cancer patients wish to die at home. The preference weakened significantly as death approached. The agreement between relatives' and GPs' accounts on patients' preferences at the end of the palliative period was 'substantial', whereas...

Trend and forecasting rate of cancer deaths at a public university hospital using univariate modeling

Science.gov (United States)

Ismail, A.; Hassan, Noor I.

2013-09-01

Cancer is one of the principal causes of death in Malaysia. This study was performed to determine the pattern of rate of cancer deaths at a public hospital in Malaysia over an 11 year period from year 2001 to 2011, to determine the best fitted model of forecasting the rate of cancer deaths using Univariate Modeling and to forecast the rates for the next two years (2012 to 2013). The medical records of the death of patients with cancer admitted at this Hospital over 11 year's period were reviewed, with a total of 663 cases. The cancers were classified according to 10th Revision International Classification of Diseases (ICD-10). Data collected include socio-demographic background of patients such as registration number, age, gender, ethnicity, ward and diagnosis. Data entry and analysis was accomplished using SPSS 19.0 and Minitab 16.0. The five Univariate Models used were Naïve with Trend Model, Average Percent Change Model (ACPM), Single Exponential Smoothing, Double Exponential Smoothing and Holt's Method. The overall 11 years rate of cancer deaths showed that at this hospital, Malay patients have the highest percentage (88.10%) compared to other ethnic groups with males (51.30%) higher than females. Lung and breast cancer have the most number of cancer deaths among gender. About 29.60% of the patients who died due to cancer were aged 61 years old and above. The best Univariate Model used for forecasting the rate of cancer deaths is Single Exponential Smoothing Technique with alpha of 0.10. The forecast for the rate of cancer deaths shows a horizontally or flat value. The forecasted mortality trend remains at 6.84% from January 2012 to December 2013. All the government and private sectors and non-governmental organizations need to highlight issues on cancer especially lung and breast cancers to the public through campaigns using mass media, media electronics, posters and pamphlets in the attempt to decrease the rate of cancer deaths in Malaysia.

Programmed death-1 & its ligands: promising targets for cancer immunotherapy.

Science.gov (United States)

Shrimali, Rajeev K; Janik, John E; Abu-Eid, Rasha; Mkrtichyan, Mikayel; Khleif, Samir N

2015-01-01

Novel strategies for cancer treatment involving blockade of immune inhibitors have shown significant progress toward understanding the molecular mechanism of tumor immune evasion. The preclinical findings and clinical responses associated with programmed death-1 (PD-1) and PD-ligand pathway blockade seem promising, making these targets highly sought for cancer immunotherapy. In fact, the anti-PD-1 antibodies, pembrolizumab and nivolumab, were recently approved by the US FDA for the treatment of unresectable and metastatic melanoma resistant to anticytotoxic T-lymphocyte antigen-4 antibody (ipilimumab) and BRAF inhibitor. Here, we discuss strategies of combining PD-1/PD-ligand interaction inhibitors with other immune checkpoint modulators and standard-of-care therapy to break immune tolerance and induce a potent antitumor activity, which is currently a research area of key scientific pursuit.

Causes of death in long-term lung cancer survivors: a SEER database analysis.

Science.gov (United States)

Abdel-Rahman, Omar

2017-07-01

Long-term (>5 years) lung cancer survivors represent a small but distinct subgroup of lung cancer patients and information about the causes of death of this subgroup is scarce. The Surveillance, Epidemiology and End Results (SEER) database (1988-2008) was utilized to determine the causes of death of long-term survivors of lung cancer. Survival analysis was conducted using Kaplan-Meier analysis and multivariate analysis was conducted using a Cox proportional hazard model. Clinicopathological characteristics and survival outcomes were assessed for the whole cohort. A total of 78,701 lung cancer patients with >5 years survival were identified. This cohort included 54,488 patients surviving 5-10 years and 24,213 patients surviving >10 years. Among patients surviving 5-10 years, 21.8% were dead because of primary lung cancer, 10.2% were dead because of other cancers, 6.8% were dead because of cardiac disease and 5.3% were dead because of non-malignant pulmonary disease. Among patients surviving >10 years, 12% were dead because of primary lung cancer, 6% were dead because of other cancers, 6.9% were dead because of cardiac disease and 5.6% were dead because of non-malignant pulmonary disease. On multivariate analysis, factors associated with longer cardiac-disease-specific survival in multivariate analysis include younger age at diagnosis (p death from primary lung cancer is still significant among other causes of death even 20 years after diagnosis of lung cancer. Moreover, cardiac as well as non-malignant pulmonary causes contribute a considerable proportion of deaths in long-term lung cancer survivors.

Relative Risks for Lethal Prostate Cancer Based on Complete Family History of Prostate Cancer Death.

Science.gov (United States)

Albright, Frederick S; Stephenson, Robert A; Agarwal, Neeraj; Cannon-Albright, Lisa A

2017-01-01

There are few published familial relative risks (RR) for lethal prostate cancer. This study estimates RRs for lethal prostate cancer based on comprehensive family history data, with the goal of improving identification of those men at highest risk of dying from prostate cancer. We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry and death certificates to estimate relative risks (RR) for death from prostate cancer based upon family history. Over 600,000 male probands were analyzed, representing a variety of family history constellations of lethal prostate cancer. RR estimates were based on the ratio of the observed to the expected number of lethal prostate cancer cases using internal rates. RRs for lethal prostate cancer based on the number of affected first-degree relatives (FDR) ranged from 2.49 (95% CI: 2.27, 2.73) for exactly 1 FDR to 5.30 (2.13, 10.93) for ≥3 affected FDRs. In an absence of affected FDRs, increased risk was also significant for increasing numbers of affected second-degree or third degree relatives. Equivalent risks were observed for similar maternal and paternal family history. This study provides population-based estimates of lethal prostate cancer risk based on lethal prostate cancer family history. Many family history constellations associated with two to greater than five times increased risk for lethal prostate cancer were identified. These lethal prostate cancer risk estimates hold potential for use in identification, screening, early diagnosis, and treatment of men at high risk for death from prostate cancer. Prostate77:41-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Early death during chemotherapy in patients with small-cell lung cancer

DEFF Research Database (Denmark)

Lassen, U N; Osterlind, K; Hirsch, F R

1999-01-01

Based on an increased frequency of early death (death within the first treatment cycle) in our two latest randomized trials of combination chemotherapy in small-cell lung cancer (SCLC), we wanted to identify patients at risk of early non-toxic death (ENTD) and early toxic death (ETD). Data were s...

Implementing a Death with Dignity program at a comprehensive cancer center.

Science.gov (United States)

Loggers, Elizabeth Trice; Starks, Helene; Shannon-Dudley, Moreen; Back, Anthony L; Appelbaum, Frederick R; Stewart, F Marc

2013-04-11

The majority of Death with Dignity participants in Washington State and Oregon have received a diagnosis of terminal cancer. As more states consider legislation regarding physician-assisted death, the experience of a comprehensive cancer center may be informative. We describe the implementation of a Death with Dignity program at Seattle Cancer Care Alliance, the site of care for the Fred Hutchinson-University of Washington Cancer Consortium, a comprehensive cancer center in Seattle that serves the Pacific Northwest. Institution-level data were compared with publicly available statewide data from Oregon and Washington. A total of 114 patients inquired about our Death with Dignity program between March 5, 2009, and December 31, 2011. Of these, 44 (38.6%) did not pursue the program, and 30 (26.3%) initiated the process but either elected not to continue or died before completion. Of the 40 participants who, after counseling and upon request, received a prescription for a lethal dose of secobarbital (35.1% of the 114 patients who inquired about the program), all died, 24 after medication ingestion (60% of those obtaining prescriptions). The participants at our center accounted for 15.7% of all participants in the Death with Dignity program in Washington (255 persons) and were typically white, male, and well educated. The most common reasons for participation were loss of autonomy (97.2%), inability to engage in enjoyable activities (88.9%), and loss of dignity (75.0%). Eleven participants lived for more than 6 months after prescription receipt. Qualitatively, patients and families were grateful to receive the lethal prescription, whether it was used or not. Overall, our Death with Dignity program has been well accepted by patients and clinicians.

Study of the association between exposure to transuranic radionuclides and cancer death

Science.gov (United States)

Fallahian, Naz Afarin

An exploratory epidemiological study has been conducted on 319 deceased nuclear workers, who had recorded intakes and histories of employment for at least one year during the time period from 1943 to 1995, at different facilities including the United States Department of Energy (DOE) sites, and thorium and uranium mining and milling plants. These workers voluntarily agreed to donate their organs or whole body to the United States Transuranium and Uranium Registries (USTUR) for scientific research purposes. The majority of this population was involved in documented radiological incidents during their careers. Many were exposed to transuranic radionuclides primarily via inhalation or puncture wounds. The purpose of this study was to find the level of dose that was received by the USTUR registrants following accidents and subsequent to mitigating actions, and to investigate whether or not there is any association between exposure to these transuranic radionuclides and cancer deaths. The external and internal dose assessments were performed using occupational radiation exposure histories and postmortem concentrations of transuranic radionuclides in critical organs, respectively. Statistical data analyses were performed to identify whether or not the USTUR registrants can be categorized as a 'low-dose' population and to investigate the potential correlation between exposure to transuranic radionuclides and causes of death within this population due to cancers of the lungs and liver as well as cancers of all sites, while controlling for the effects of other confounders. Based on the statistical tests performed, the USTUR registrants can be categorized as a low-dose population in terms of their occupational external exposures. However, when considering their total effective dose equivalents from both external penetrating radiation and internal exposure to transuranic radionuclides, they can not be categorized as a low-dose population with a 95% confidence level (alpha = 0

Mechanisms underlying 3-bromopyruvate-induced cell death in colon cancer.

Science.gov (United States)

Sun, Yiming; Liu, Zhe; Zou, Xue; Lan, Yadong; Sun, Xiaojin; Wang, Xiu; Zhao, Surong; Jiang, Chenchen; Liu, Hao

2015-08-01

3-Bromopyruvate (3BP) is an energy-depleting drug that inhibits Hexokinase II activity by alkylation during glycolysis, thereby suppressing the production of ATP and inducing cell death. As such, 3BP can potentially serve as an anti-tumorigenic agent. Our previous research showed that 3BP can induce apoptosis via AKT /protein Kinase B signaling in breast cancer cells. Here we found that 3BP can also induce colon cancer cell death by necroptosis and apoptosis at the same time and concentration in the SW480 and HT29 cell lines; in the latter, autophagy was also found to be a mechanism of cell death. In HT29 cells, combined treatment with 3BP and the autophagy inhibitor 3-methyladenine (3-MA) exacerbated cell death, while viability in 3BP-treated cells was enhanced by concomitant treatment with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (z-VAD-fmk) and the necroptosis inhibitor necrostatin (Nec)-1. Moreover, 3BP inhibited tumor growth in a SW480 xenograft mouse model. These results indicate that 3BP can suppress tumor growth and induce cell death by multiple mechanisms at the same time and concentration in different types of colon cancer cell by depleting cellular energy stores.

NIH study finds that coffee drinkers have lower risk of death

Science.gov (United States)

Older adults who drank coffee -- caffeinated or decaffeinated -- had a lower risk of death overall than others who did not drink coffee, according a study by researchers from the National Cancer Institute (NCI), part of the National Institutes of Health,

Causes of Cancer Death Among First-Degree Relatives in Japanese Families with Lynch Syndrome.

Science.gov (United States)

Tanakaya, Kohji; Yamaguchi, Tatsuro; Ishikawa, Hideki; Hinoi, Takao; Furukawa, Yoichi; Hirata, Keiji; Saida, Yoshihisa; Shimokawa, Mototsugu; Arai, Masami; Matsubara, Nagahide; Tomita, Naohiro; Tamura, Kazuo; Sugano, Kokichi; Ishioka, Chikashi; Yoshida, Teruhiko; Ishida, Hideyuki; Watanabe, Toshiaki; Sugihara, Kenichi

2016-04-01

To elucidate the causes of cancer death in Japanese families with Lynch syndrome (LS). The distributions of cancer deaths in 485 individuals from 67 families with LS (35, 30, and two families with MutL homologue 1 (MLH1), MSH2, and MSH6 gene mutations, respectively), obtained from the Registry of the Japanese Society for Cancer of the Colon and Rectum were analyzed. Among 98 cancer deaths of first-degree relatives of unknown mutation status, 53%, 19%, 13% (among females), 7% (among females) and 5% were due to colorectal, gastric, uterine, ovarian, and hepatobiliary cancer, respectively. The proportion of deaths from extra-colonic cancer was significantly higher in families with MSH2 mutation than in those with MLH1 mutation (p=0.003). In addition to colonic and uterine cancer, management and surveillance targeting gastric, ovarian and hepatobiliary cancer are considered important for Japanese families with LS. Extra-colonic cancer in families with MSH2 mutation might require for more intensive surveillance. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

An analysis of cancer death risk among medical diagnostic X-ray workers in China, 1950-1995

International Nuclear Information System (INIS)

Zhao Yongcheng; Wang Jixian; Zhang Wei; Li Benxiao; Fan Tiqiang; Zhang Jingyuan

2002-01-01

Objective: To investigate effects of occupational radiation exposure on cancer death among medical diagnostic X-ray workers. Methods: A cohort study on medical diagnostic X-ray workers and non-X-ray medical workers was carried out and a risk analysis of cancer death between 1950 and 1995 was conducted with the O/E system. Results: A significant enhancement in cancer death risk for X-ray workers was found, especially those engaged in X-ray work in early calendar years. The overall cancer RR was 1.26, (95 % CI: 1.14 - 1.38), for leukemia it was 2.48, (95% CI: 1.68-3.51 ); for esophagus cancer, 3.18, (95% CI: 2.02 -4.77); for liver cancer, 1.54, (95 % CI: 1.27 - 1.86); and for bone cancer, 2.48, (95 % CI: 1.00 - 5.40). In the late calendar year cohort a significant enhancement of cancer death was seen only in esophagus cancer (RR = 4.19, 95 % CI: 1.80 - 8.25) and lung cancer (RR = 1.60, 95% CI:1.10-2.25). Conclusion: Long-term occupational X-ray irradiation can enhance the risk of cancer death when the cumulative dose reached a certain level. The significant enhancement of cancer death for leukemia and some solid cancers may be related to the occupational exposure to X-rays

Nitrates in drinking water and the risk of death from rectal cancer: does hardness in drinking water matter?

Science.gov (United States)

Chang, Chih-Ching; Chen, Chih-Cheng; Wu, Deng-Chuang; Yang, Chun-Yuh

2010-01-01

The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and increased risk of death from rectal cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of nitrate on development of rectal cancer. A matched case-control study was used to investigate the relationship between the risk of death from rectal cancer and exposure to nitrate in drinking water in Taiwan. All rectal cancer deaths of Taiwan residents from 2003 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO(3)-N), Ca, and Mg in drinking water was collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO(3)-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO(3)-N exposure level was cancer occurrence was 1.15 (1.01-1.32) for individuals who resided in municipalities served by drinking water with a NO(3)-N exposure > or =0.38 ppm. There was no apparent evidence of an interaction between drinking water NO(3)-N levels with low Mg intake via drinking water. However, evidence of a significant interaction was noted between drinking-water NO(3)-N concentrations and Ca intake via drinking water. Our findings showed that the correlation between NO(3)-N exposure and risk of rectal cancer development was influenced by Ca in drinking water. This is the first study to report effect modification by Ca intake from drinking water on the association between NO(3)-N exposure and risk of rectal cancer occurrence. Increased knowledge of the mechanistic interaction between Ca and NO(3)-N in reducing rectal cancer risk will aid in public policymaking and setting

Nitrate in drinking water and risk of death from pancreatic cancer in Taiwan.

Science.gov (United States)

Yang, Chun-Yuh; Tsai, Shang-Shyue; Chiu, Hui-Fen

2009-01-01

The relationship between nitrate levels in drinking water and risk of pancreatic cancer development remains inconclusive. A matched case-control and nitrate ecology study was used to investigate the association between mortality attributed to pancreatic cancer and nitrate exposure from Taiwan's drinking water. All pancreatic cancer deaths of Taiwan residents from 2000 through 2006 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on nitrate-nitrogen (NO(3)-N) levels of drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios and confidence limits for pancreatic cancer death for those with high nitrate levels in their drinking water, as compared to the lowest tertile, were 1.03 (0.9-1.18) and 1.1 (0.96-1.27), respectively. The results of the present study show that there was no statistically significant association between the levels of nitrate in drinking water and increased risk of death from pancreatic cancer.

Alcohol-attributable cancer deaths under 80 years of age in New Zealand.

Science.gov (United States)

Connor, Jennie; Kydd, Robyn; Maclennan, Brett; Shield, Kevin; Rehm, Jürgen

2017-05-01

Cancer deaths made up 30% of all alcohol-attributable deaths in New Zealanders aged 15-79 years in 2007, more than all other chronic diseases combined. We aimed to estimate alcohol-attributable cancer mortality and years of life lost by cancer site and identify differences between Māori and non-Māori New Zealanders. We applied the World Health Organization's comparative risk assessment methodology at the level of Māori and non-Māori subpopulations. Proportions of specific alcohol-related cancers attributable to alcohol were calculated by combining alcohol consumption estimates from representative surveys with relative risks from recent meta-analyses. These proportions were applied to both 2007 and 2012 mortality data. Alcohol consumption was responsible for 4.2% of all cancer deaths under 80 years of age in 2007. An average of 10.4 years of life was lost per person; 12.7 years for Māori and 10.1 years for non-Māori. Half of the deaths were attributable to average consumption of strategies to reduce ethnic disparities in risk and outcome are needed in New Zealand. [Connor J, Kydd R, Maclennan B, Shield K, Rehm J. Alcohol-attributable cancer deaths under 80 years of age in New Zealand. Drug Alcohol Rev 2017;36:415-423]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

Lung cancer death rates among nonsmokers and pipe and cigarette smokers

Energy Technology Data Exchange (ETDEWEB)

Stocks, P; Campbell, J M

1955-01-01

This report discusses a two-year comparison of deaths from lung cancer with environmental histories, including smoking and pollution character of residence, of British men aged 45 to 74. In rural areas, lung cancer increases almost linearly with smoking, the increment being 1 death per 1000 for each 13 cigarettes. Pipe smoking is about 1/3 as hazardous as cigarette-smoking. In mixed rural-urban areas, rates in light and moderate smokers were higher than rural but not so with pipe or heavy smokers. There was a higher death rate in every group in urban area, but rate of mortality increase with increasing cigarette exposure was greater for those living in rural areas. Urban/rural ratio was about 9 for nonsmokers decreasing to almost 1 for heavy smokers. Smoking contributes 1/2 of lung cancer in urban area; urban factor contributes 3/8 (absolute excess in every group). Benzopyrene concentration of urban area was 8 to 11 times that of rural areas and gradient corresponds to urban/rural ratio for nonsmokers. Benzopyrene/death correlation was good if assumed combined intake is considered.

Non-natural manners of death among users of illicit drugs: Substance findings.

Science.gov (United States)

Delaveris, Gerd Jorunn M; Teige, Brita; Rogde, Sidsel

2014-05-01

The aim of the study was to explore differences and similarities between the various non-natural manners of death (accident, suicide, homicide) regarding toxicological findings in illicit drug users. Medicolegal autopsy reports from the Institute of Forensic Medicine University of Oslo concerning deaths from 2000 to 2009 were investigated. Those aged 20-59 whose manner of death was non-natural and who tested positive for any narcotic drug (morphine/heroin, amphetamines, ecstasy, cannabis, LSD, PCP, and high levels of GHB in addition to methadone and buprenorphine) were selected. All substance findings were registered and categorized (narcotics, ethanol, and medicinal products). Of the 1603 autopsies that met the selection criteria, 1204 were accidental intoxications, 122 accidents other than intoxication, 114 suicides by intoxication, 119 non-intoxication suicides, and 44 victims of homicide. Poly drug use was found in all manners of death. The drug profile as well as the mean number of substances (illicit drugs and medicinal products) varied from 2.9 to 4.6 substances per case, depending on the manner of death. Intoxication suicides had the highest number of substances and a total drug profile similar to accidental intoxications. Non-intoxication suicides had a total drug profile similar to homicide and accidents other than intoxication. The number of substances found per case increased during the decade, mainly due to increased findings of methadone, cannabis, amphetamines, and benzodiazepines. Methadone findings increased much more than buprenorphine. Methadone was found 20 times more often than buprenorphine in accidental intoxication cases. In summary, poly drug findings are common in adults who suffer a non-natural death while using illicit drugs. The different manners of death have some specific characteristics and significant differences regarding drug profile. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Cytokines in immunogenic cell death: Applications for cancer immunotherapy.

Science.gov (United States)

Showalter, Anne; Limaye, Arati; Oyer, Jeremiah L; Igarashi, Robert; Kittipatarin, Christina; Copik, Alicja J; Khaled, Annette R

2017-09-01

Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions. Natural Killer (NK) cells are a front-line defense against drug-resistant tumors and can provide tumoricidal activity to enhance tumor immune surveillance. Cytokines like IFN-γ or TNF play a crucial role in creating an immunogenic microenvironment and therefore are key players in the fight against metastatic cancer. To this end, a group of anthracyclines or treatments like photodynamic therapy (PDT) exert their effects on cancer cells in a manner that activates the immune system. This process, known as immunogenic cell death (ICD), is characterized by the release of membrane-bound and soluble factors that boost the function of immune cells. This review will explore different types of ICD inducers, some in clinical trials, to demonstrate that optimizing the cytokine response brought about by treatments with ICD-inducing agents is central to promoting anti-cancer immunity that provides long-lasting protection against disease recurrence and metastasis. Copyright © 2017. Published by Elsevier Ltd.

Case-control study of cancer deaths in high background radiation areas of China

International Nuclear Information System (INIS)

Tao Zufan; Cha Yongru; Zhou Shunyuan

1989-01-01

This paper presents the results of a case-control study of deaths from liver, stomach and lung cancers in the high background radiation areas (HBRA) in Yangjiang County and neighboring control areas (CA). The purpose of this study was to explore the probable relationship between the cancer deaths and the environmental mutation-related factors in the two areas, so that the role of elevated natural radiation in cancer mortality could be properly ascertained. The studied numbers of cases of liver, stomach and lung cancers were 64, 28 and 17 in HBRA, and 75, 36 and 13 in CA, respectively. The proportion of the number of cases to that of the controls was 1:1 for liver cancer and 1:2 for cancers of stomach and lung. The factors studied included pesticide, smoking, alcohol consumption, medical X-ray exposure, diet, and the socioeconomic status, such as occupation, education, economic income, living space etc. The data for this study were collected through interviewing. The data collected were analysed by methods of matched and unmatched studies. The results expressed by odds ratio (OR) show that there is no significant between most factors studied and cancer deaths, although the associations of desths from stomach cancer with drinking water of nonwell source and of lung cancer with alcohol consumption in HBRA, and the associations of liver cancer deaths with occupations involving poisonous and noxious substances, pesticide and alcohol, and of lung cancer with pesticide and lower family income in CA can be found. This study has provided some clues for explaining the difference in cancer mortalities between HBRA and CA

Views on life and death of physicians, nurses, cancer patients and general population in Japan.

Science.gov (United States)

Sekiya, Noriyasu; Kuroda, Yujiro; Nakajima, Kasumi; Iwamitsu, Yumi; Kanai, Yoshiaki; Miyashita, Mitsunori; Kotani, Midori; Kitazawa, Yutaka; Yamashita, Hideomi; Nakagawa, Keiichi

2017-01-01

This study aimed to investigate views on life and death among physicians, nurses, cancer patients, and the general population in Japan and examine factors affecting these views. We targeted 3,140 physicians, 470 nurses, 450 cancer patients, and 3,000 individuals from the general population. We used the Death Attitudes Inventory (DAI) to measure attitudes toward life and death. The collection rates were 35% (1,093/3,140), 78% (366/470), 69% (310/450), and 39% (1,180/3,000) for physicians, nurses, patients, and the general population, respectively. We found that age, sex, social role (i.e., physician, nurse, cancer patient, and general population) were significantly correlated with DAI subscales. Compared with general population, attitudes toward death of physicians, nurses and cancer patients differed significantly even after adjusted their age and sex. Our study is the first to analyze differences in views on life and death among physicians, nurses, cancer patients, and the general population in Japan.

Place of death of pediatric cancer patients in a single institute during 7 years.

Science.gov (United States)

Yanai, Tomoko; Hirase, Satoshi; Matsunoshita, Natsuki; Yamamoto, Nobuyuki; Ninchoji, Takeshi; Kubokawa, Ikuko; Mori, Takeshi; Hayakawa, Akira; Takeshima, Yasuhiro; Iijima, Kazumoto; Matsuo, Masafumi

2012-06-27

Place of death is an important issue at the end-of-life. It is poorly understood in pediatric cancer patients in Japan. This study aimed to clarify place of death of children with cancer as well as variables associated with place of death. Study population was pediatric cancer patients who died in the Department of Pediatrics at Kobe University Hospital during the last 7 years. The medical records were retrospectively reviewed regardless of cause of death to derive data relating to patients' characteristics and disease. 18 patients were included. Median age at death was 12.2 years old. 6 patients including 5 children in complete remission had hematological disease and 12 patients suffered from solid tumors. 4 patients (22.2%) died at home, whereas 14 patients (77.8%) died in the hospital including 6 ICU deaths. No one died in hospices. Preference of patients was unavailable due to the lack of inquiry. Factors influencing place of death (home, ICU, non-ICU) were disease (hematological disease vs. solid tumor, p=0.010, brain tumor vs. non-brain tumor, p=0.023), disease status (complete remission vs. non-complete remission, p=0.0014) and preference of families (p=0.029). Among 6 families who expressed preference, no disparity was observed between actual and preferred place of death. This is the first English publication of place of death of pediatric cancer patients in Japan. The low percentage of home death, factors influencing place of death and the lack of disparity between actual and preferred place of death were indicated. Further studies are required to better understand place of death.

Inequalities in Cancer Deaths by Age, Gender and Education.

Science.gov (United States)

Gróf, Marek; Vagašová, Tatiana; Oltman, Marián; Skladaný, Ľubomír; Maličká, Lenka

2017-12-01

The economy of each state provides a significant amount of money into the health care system with the aim of knowing the health status of its population in the context of socioeconomic characteristics for effective resource allocation. In recent years, there is a growing number of cancer deaths in Slovakia. Therefore, the structure of cancer deaths according to its primary determinants, such as age, sex and education with the aim of effective implementation of prevention programs in Slovakia was examined. Main source of data on deaths from 1996 to 2014 was provided by National Health Information Centre in Slovakia. However, data were available only from 2011. Standardized mortality rate per 100,000 inhabitants was estimated by the method of direct standardization using European standard population. The R project for statistical computing was used for calculation of statistically significant differences among various groups of mortality. The results show that people with primary education die from cancer later than people with higher education. However, major differences related to both sex and age are present in people with university education. A different variety of cancers occur in childhood (neoplasm of brain), adolescents (neoplasm of bone), young adults (neoplasm of brain), or adults (lung cancer and breast cancer). Malignant neoplasm of brain was more prevalent at higher education levels, Malignant neoplasm of bladder and Malignant melanoma of skin were more prevalent at the university level of education. The results can be useful for economists to define the health priorities in each country, make the financial decisions in economics, and thus contribute to better health, economic growth, as well as effective spending of health expenditures. Copyright© by the National Institute of Public Health, Prague 2017.

Association between shift work and the risk of death from biliary tract cancer in Japanese men.

Science.gov (United States)

Lin, Yingsong; Nishiyama, Takeshi; Kurosawa, Michiko; Tamakoshi, Akiko; Kubo, Tatsuhiko; Fujino, Yoshihisa; Kikuchi, Shogo

2015-10-21

There is increasing evidence suggesting that shift work involving night work may increase cancer risk. We examined the association between working rotating shifts and the risk of death from biliary tract cancer among Japanese men who participated in the Japan Collaborative Cohort Study. Of the 46,395 men recruited, 22,224 men aged 40-65 at baseline (1988-1990) who reported working full-time or were self-employed were included in the present analysis. The study subjects were followed through December 31, 2009. Information regarding occupation and lifestyle factors was collected using a self-administered questionnaire. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for the risk of death from biliary tract cancer in relation to shift work. During a mean 17-year follow-up, we observed 94 biliary tract cancer deaths, including 23 deaths from gallbladder cancer and 71 deaths from extrahepatic bile duct cancer. Overall, shift work was associated with a statistically non-significant increase in the risk of biliary tract cancer, with an HR of 1.50 (95 % CI: 0.81-2.77), among rotating shift workers. When the analysis was limited to extrahepatic bile duct cancer, a significant association appeared, with a multivariable-adjusted HR of 1.93 (95 % CI: 1.00-3.72) for rotating shift workers. Our data indicate that shift work may be associated with increased risk of death from extrahepatic bile duct cancer in this cohort of Japanese men. The association with gallbladder cancer remains unclear because of the small number of deaths.

CERT depletion predicts chemotherapy benefit and mediates cytotoxic and polyploid‐specific cancer cell death through autophagy induction

DEFF Research Database (Denmark)

Lee, Alvin J. X.; Roylance, Rebecca; Sander, Jil

2012-01-01

cell microscopy analysis revealed that CERT depletion induces LAMP2‐dependent death of polyploid cells following exit from mitosis in the presence of paclitaxel. We find that CERT is relatively over‐expressed in HER2+ breast cancer and CERT protein expression acts as an independent prognostic variable...

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

Energy Technology Data Exchange (ETDEWEB)

Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Mok, Tony S.K. [Department of Clinical Oncology, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Warner, Timothy D. [The William Harvey Research Institute, Queen Mary University of London, London (United Kingdom); Underwood, Malcolm J. [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong); Chen, George G., E-mail: gchen@cuhk.edu.hk [Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories (Hong Kong)

2009-10-15

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB{sub 2}) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB{sub 2} but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27

International Nuclear Information System (INIS)

Leung, Kin Chung; Hsin, Michael K.Y.; Chan, Joey S.Y.; Yip, Johnson H.Y.; Li, Mingyue; Leung, Billy C.S.; Mok, Tony S.K.; Warner, Timothy D.; Underwood, Malcolm J.; Chen, George G.

2009-01-01

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB 2 ) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB 2 but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.

Why is the death rate from lung cancer falling in the Russian Federation?

Science.gov (United States)

Shkolnikov, V; McKee, M; Leon, D; Chenet, L

1999-03-01

Age standardised death rates (European standard population) from lung cancer in the Russian Federation, have been rising since at least 1965, levelled out in the late 1980s and have subsequently decreased. The reasons for this decline are not apparent. This study seeks to identify the reasons for the decline in mortality from lung cancer in the Russian Federation in the 1990s. Changes in age-specific mortality from lung cancer in the Russian Federation between 1990 are described and age-cohort analysis, based on age-specific death rates for lung cancer is undertaken for the period 1965 to 1995. As other work has shown that any recent deterioration in coding of cause of death has been confined largely to the elderly, this suggests that the trend is not a coding artefact. Age-period-cohort analysis demonstrates the existence of a marked birth cohort effect, with two major peaks corresponding to those born around 1926 and 1938. These groups would have reached their early teens during the second world war and the period immediately after the death of Stalin, respectively. The present downward trend in death rates from lung cancer in the Russian Federation is partly due to a cohort effect and it is expected that this will soon reverse, with a second peak occurring in about 2003.

Death Anxiety and Quality of Life in Iranian Caregivers of Patients With Cancer.

Science.gov (United States)

Soleimani, Mohammad Ali; Lehto, Rebecca H; Negarandeh, Reza; Bahrami, Nasim; Chan, Yiong Huak

Concerns about death may alienate and negatively impact communication among family members of patients with life-threatening illness. Little is known about the relationship of death anxiety to quality of life in cancer family caregivers. The aim of this study was to examine relationships between sociodemographic and patient-related factors, social support, and religiosity with death anxiety and quality of life in Iranian cancer family caregivers. Three hundred thirty family caregivers from an urban regional cancer institute in Iran participated in a descriptive-correlational study that incorporated sociodemographic surveys and validated death anxiety (Templer Scale) and Quality of life (Family Version) instruments. Caregivers reported moderate levels of death anxiety and decrements in QOL. Quality of life was inversely associated with death anxiety (r = -0.30, P quality of life. Death anxiety is associated with lowered quality of life in Iranian family caregivers. Multiple factors may impact death anxiety and quality of life relevant to the socioreligious milieu. Addressing concerns that increase death anxiety may improve quality of life and lower stress associated with adapting to the family caregiver role. Caregiving responsibilities, added to challenges associated with personal, family, and professional life, impact multiple aspects of QOL. As nurses increasingly care for patients from diverse backgrounds, it becomes more imperative that support for family caregivers that promotes psychological adaptation and quality of life is needed.

Hyoid Displacement in Post-Treatment Cancer Patients: Preliminary Findings

Science.gov (United States)

Zu, Yihe; Yang, Zhenyu; Perlman, Adrienne L.

2011-01-01

Purpose: Dysphagia after head and neck cancer treatment is a health care issue; in some cases, the cause of death is not cancer but, rather, the passage of food or liquid into the lungs. Hyoid displacement is known to be important to safe swallowing function. The purpose of this study was to evaluate hyoid displacement after cancer treatment.…

Cancer Deaths due to Lack of Universal Access to Radiotherapy in the Brazilian Public Health System.

Science.gov (United States)

Mendez, L C; Moraes, F Y; Fernandes, G Dos S; Weltman, E

2018-01-01

Radiotherapy plays a fundamental role in the treatment of cancer. Currently, the Brazilian public health system cannot match the national radiotherapy demand and many patients requiring radiotherapy are never exposed to this treatment. This study estimated the number of preventable deaths in the public health system if access to radiotherapy was universal. Incidence rates for the year 2016 provided by Instituto Nacional de Cancer were used in this analysis. The number of untreated patients requiring radiotherapy was obtained through the difference between the total number of patients requiring radiotherapy and the total amount of delivered radiotherapy treatments in the public health system. The number of deaths for the three most common cancers in each gender due to radiotherapy shortage was calculated. Initially, the total number of patients per cancer type was divided in stages using Brazilian epidemiological data. Subsequently, previously published tree arm diagrams were used to define the rate of patients requiring radiotherapy in each specific clinical setting. Finally, the clinical benefit of radiotherapy in overall survival was extracted from studies with level 1 evidence. Over 596 000 cancer cases were expected in Brazil in 2016. The public health system covers more than 75% of the Brazilian population and an estimated 111 432 patients who required radiotherapy in 2016 did not receive this treatment. Breast, colorectal and cervix cancers are the most frequent malignant tumours in women and prostate, lung and colorectal in men. The number of deaths due to a radiotherapy shortage in the year 2016 for these types of cancer were: (i) breast: 1011 deaths in 10 years; (ii) cervix: 2006 deaths in 2 years; (iii) lung: 1206 deaths in 2 years; (iv) prostate, intermediate risk: 562 deaths in 13 years; high risk: 298 deaths in 10 years; (v) colorectal: 0 deaths, as radiotherapy has no proven benefit in overall survival. Thousands of cancer patients requiring

Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Curry, Merril C.; Peters, Amelia A. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Kenny, Paraic A. [Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Roberts-Thomson, Sarah J. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Monteith, Gregory R., E-mail: gregm@uq.edu.au [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia)

2013-05-10

Highlights: •Some clinical breast cancers are associated with MCU overexpression. •MCU silencing did not alter cell death initiated with the Bcl-2 inhibitor ABT-263. •MCU silencing potentiated caspase-independent cell death initiated by ionomycin. •MCU silencing promoted ionomycin-mediated cell death without changes in bulk Ca{sup 2+}. -- Abstract: The mitochondrial calcium uniporter (MCU) transports free ionic Ca{sup 2+} into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU. Silencing of MCU expression in the basal-like MDA-MB-231 breast cancer cell line produced no change in proliferation or cell viability. However, distinct consequences of MCU silencing were seen on cell death pathways. Caspase-dependent cell death initiated by the Bcl-2 inhibitor ABT-263 was not altered by MCU silencing; whereas caspase-independent cell death induced by the calcium ionophore ionomycin was potentiated by MCU silencing. Measurement of cytosolic Ca{sup 2+} levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca{sup 2+} levels. This study demonstrates that MCU overexpression is a feature of some breast cancers and that MCU overexpression may offer a survival advantage against some cell death pathways. MCU inhibitors may be a strategy to increase the effectiveness of therapies that act through the induction of caspase-independent cell death pathways in estrogen receptor negative and basal-like breast cancers.

Cystine addiction of triple-negative breast cancer associated with EMT augmented death signaling.

Science.gov (United States)

Tang, X; Ding, C-K; Wu, J; Sjol, J; Wardell, S; Spasojevic, I; George, D; McDonnell, D P; Hsu, D S; Chang, J T; Chi, J-T

2017-07-27

Despite the advances in the diagnosis and treatment of breast cancer, breast cancers still cause significant mortality. For some patients, especially those with triple-negative breast cancer, current treatments continue to be limited and ineffective. Therefore, there remains an unmet need for a novel therapeutic approach. One potential strategy is to target the altered metabolic state that is rewired by oncogenic transformation. Specifically, this rewiring may render certain outside nutrients indispensable. To identify such a nutrient, we performed a nutrigenetic screen by removing individual amino acids to identify possible addictions across a panel of breast cancer cells. This screen revealed that cystine deprivation triggered rapid programmed necrosis, but not apoptosis, in the basal-type breast cancer cells mostly seen in TNBC tumors. In contrast, luminal-type breast cancer cells are cystine-independent and exhibit little death during cystine deprivation. The cystine addiction phenotype is associated with a higher level of cystine-deprivation signatures noted in the basal type breast cancer cells and tumors. We found that the cystine-addicted breast cancer cells and tumors have strong activation of TNFα and MEKK4-p38-Noxa pathways that render them susceptible to cystine deprivation-induced necrosis. Consistent with this model, silencing of TNFα and MEKK4 dramatically reduces cystine-deprived death. In addition, the cystine addiction phenotype can be abrogated in the cystine-addictive cells by miR-200c, which converts the mesenchymal-like cells to adopt epithelial features. Conversely, the introduction of inducers of epithelial-mesenchymal transition (EMT) in cystine-independent breast cancer cells conferred the cystine-addiction phenotype by modulating the signaling components of cystine addiction. Together, our data reveal that cystine-addiction is associated with EMT in breast cancer during tumor progression. These findings provide the genetic and

Deaths of cancer cells observed after X-Ray irradiation

International Nuclear Information System (INIS)

Kuwahara, Yoshikazu; Oikawa, Toshiyuki; Ochiai, Yasushi; Fukumoto, Motoi; Kurihara, Ai; Noma, Naoto; Shimura, Tsutomu; Fukumoto, Manabu; Ohkubo, Yasuhito

2011-01-01

Radiation induces cell death by apoptosis, autophagy (autophagic cell death, APCD), necrosis, which are respectively called type I, II, III programmed cell death, senescence, mitotic catastrophe, etc. This paper mainly describes details of authors' studies on APCD of clinically relevant radioresistant (CRR) HepG2-8960-R cells established from proliferating survivor even after repeated X-irradiation of >30 days x 2 Gy/day to the parent HepG2 cells. Autophagy forms autophagosome where many proteins are thoroughly degraded differing from proteasomal ubiquitin system, has been known essentially related to death and survival of injured cells under certain tissue conditions, and is distinguishable from other modes of cell death by morphological and cytochemical means. One of important authors' findings is as follows. APCD of CRR cells is normally seen in 20% and of the parent strain, 5%. When they are X-irradiated at 10 Gy, APCD of the latter is more (70%) than the former (40%), and no APCD is induced by 2 Gy x 5 days in the former in contrast to the latter. APCD by radiation is thus conceivably suppressed in CRR cells, suggesting that their radioresistance can be reversed by treatment to induce APCD. Autophagy is usually suppressed by mammalian target of rapamycin (mTOR), and when CRR cells are treated with rapamycin, they become radiosensitive to the comparable level to the parent HepG2. When HepG2 cells are treated with 3-methyladenine, an inhibitor of autophagy, or Beclin siRNA, they become radioresistant. For effectiveness of APCD induction and suppression on cancer therapy, results are contradictory in certain reports and autophagy should be a problem to be further elucidated from radiation biology aspect. (author)

Calcium regulates cell death in cancer: Roles of the mitochondria and mitochondria-associated membranes (MAMs).

Science.gov (United States)

Danese, Alberto; Patergnani, Simone; Bonora, Massimo; Wieckowski, Mariusz R; Previati, Maurizio; Giorgi, Carlotta; Pinton, Paolo

2017-08-01

Until 1972, the term 'apoptosis' was used to differentiate the programmed cell death that naturally occurs in organismal development from the acute tissue death referred to as necrosis. Many studies on cell death and programmed cell death have been published and most are, at least to some degree, related to cancer. Some key proteins and molecular pathways implicated in cell death have been analyzed, whereas others are still being actively researched; therefore, an increasing number of cellular compartments and organelles are being implicated in cell death and cancer. Here, we discuss the mitochondria and subdomains of the endoplasmic reticulum (ER) that interact with mitochondria, the mitochondria-associated membranes (MAMs), which have been identified as critical hubs in the regulation of cell death and tumor growth. MAMs-dependent calcium (Ca 2+ ) release from the ER allows selective Ca 2+ uptake by the mitochondria. The perturbation of Ca 2+ homeostasis in cancer cells is correlated with sustained cell proliferation and the inhibition of cell death through the modulation of Ca 2+ signaling. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux. Copyright © 2017 Elsevier B.V. All rights reserved.

Esophageal cancer among Brazilian agricultural workers: case-control study based on death certificates.

Science.gov (United States)

Meyer, Armando; Alexandre, Pedro Celso Braga; Chrisman, Juliana de Rezende; Markowitz, Steven B; Koifman, Rosalina Jorge; Koifman, Sergio

2011-03-01

Several studies suggest that agricultural workers are at higher risk to develop and die by certain types of cancer. Esophageal cancer is not commonly listed among these types. However, some recent studies indicated that if there is an association between agricultural working and esophageal cancer, it s more likely to be observed among workers highly exposed to pesticides. In the present study, the magnitude of the association between agricultural working and esophageal cancer mortality was evaluated in a high pesticide use area in Brazil, through a death certificate-based case-control study. Cases were individuals from both genders, 30-59 years old, for whom basic cause of death was ascertained as cancer of the esophagus. For each case, one control was randomly selected from all possible controls for which the basic cause of death was ascertained as different from neoplasm and diseases of the digestive system. In addition, controls matched their cases by sex, age, year of death, and state of residence. Crude and adjusted odds ratios were then calculated to estimate the magnitude of the risk. Results showed that, in general, agricultural workers were at significantly higher risk to die by esophageal cancer, when compared to non-agricultural workers. Stratified analysis also revealed that the magnitude of such risk was slightly higher among illiterate agricultural workers, and simultaneous adjustment for several covariates showed that the risk was quantitatively higher among younger southern agricultural workers. These results suggest the esophageal cancer may be included among those types of cancer etiologically associated to agricultural working. Copyright © 2010 Elsevier GmbH. All rights reserved.

Radon and risk of death from cancer and cardiovascular diseases in the German uranium miners cohort study. Follow-up 1946-2003

International Nuclear Information System (INIS)

Kreuzer, Michaela; Grosche, B.; Schnelzer, M.; Tschense, A.; Dufey, F.; Walsh, L.

2010-01-01

Data from the German uranium miners cohort study were analyzed to investigate the radon-related risk of mortality from cancer and cardiovascular diseases. The Wismut cohort includes 58,987 men who were employed for at least 6 months from 1946 to 1989 at the former Wismut uranium mining company in Eastern Germany. By the end of 2003, a total of 3,016 lung cancer deaths, 3,355 deaths from extrapulmonary cancers, 5,141 deaths from heart diseases and 1,742 deaths from cerebrovascular diseases were observed. Although a number of studies have already been published on various endpoints in the Wismut cohort, the aim of the present analyses is to provide a direct comparison of the magnitude of radon-related risk for different cancer sites and cardiovascular diseases using the same data set, the same follow-up period and the same statistical methods. A specific focus on a group of cancers of the extrathoracic airways is also made here, due to the assumed high organ doses from absorbed radon progeny. Internal Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative exposure to radon in working level months (WLM) and its 95% confidence limits (CI). There was a statistically significant increase in the risk of lung cancer with increasing radon exposure (ERR/WLM = 0.19%; 95% CI: 0.17%; 0.22%). A smaller, but also statistically significant excess was found for cancers of the extrathoracic airways and trachea (ERR/WLM = 0.062%; 95% CI: 0.002%; 0.121%). Most of the remaining nonrespiratory cancer sites showed a positive relationship with increasing radon exposure, which, however, did not reach statistical significance. No increase in risk was noted for coronary heart diseases (ERR/WLM = 0.0003%) and cerebrovascular diseases (ERR/WLM = 0.001%). The present data provide clear evidence of an increased radon-related risk of death from lung cancer, some evidence for an increased radon-related risk of death from cancers of the extrathoracic airways

Radon and risk of death from cancer and cardiovascular diseases in the German uranium miners cohort study: follow-up 1946-2003.

Science.gov (United States)

Kreuzer, Michaela; Grosche, B; Schnelzer, M; Tschense, A; Dufey, F; Walsh, L

2010-05-01

Data from the German uranium miners cohort study were analyzed to investigate the radon-related risk of mortality from cancer and cardiovascular diseases. The Wismut cohort includes 58,987 men who were employed for at least 6 months from 1946 to 1989 at the former Wismut uranium mining company in Eastern Germany. By the end of 2003, a total of 3,016 lung cancer deaths, 3,355 deaths from extrapulmonary cancers, 5,141 deaths from heart diseases and 1,742 deaths from cerebrovascular diseases were observed. Although a number of studies have already been published on various endpoints in the Wismut cohort, the aim of the present analyses is to provide a direct comparison of the magnitude of radon-related risk for different cancer sites and cardiovascular diseases using the same data set, the same follow-up period and the same statistical methods. A specific focus on a group of cancers of the extrathoracic airways is also made here, due to the assumed high organ doses from absorbed radon progeny. Internal Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative exposure to radon in working level months (WLM) and its 95% confidence limits (CI). There was a statistically significant increase in the risk of lung cancer with increasing radon exposure (ERR/WLM = 0.19%; 95% CI: 0.17%; 0.22%). A smaller, but also statistically significant excess was found for cancers of the extrathoracic airways and trachea (ERR/WLM = 0.062%; 95% CI: 0.002%; 0.121%). Most of the remaining nonrespiratory cancer sites showed a positive relationship with increasing radon exposure, which, however, did not reach statistical significance. No increase in risk was noted for coronary heart diseases (ERR/WLM = 0.0003%) and cerebrovascular diseases (ERR/WLM = 0.001%). The present data provide clear evidence of an increased radon-related risk of death from lung cancer, some evidence for an increased radon-related risk of death from cancers of the extrathoracic airways

Attributing death to cancer: cause-specific survival estimation.

Directory of Open Access Journals (Sweden)

Mathew A

2002-10-01

Full Text Available Cancer survival estimation is an important part of assessing the overall strength of cancer care in a region. Generally, the death of a patient is taken as the end point in estimation of overall survival. When calculating the overall survival, the cause of death is not taken into account. With increasing demand for better survival of cancer patients it is important for clinicians and researchers to know about survival statistics due to disease of interest, i.e. net survival. It is also important to choose the best method for estimating net survival. Increase in the use of computer programmes has made it possible to carry out statistical analysis without guidance from a bio-statistician. This is of prime importance in third- world countries as there are a few trained bio-statisticians to guide clinicians and researchers. The present communication describes current methods used to estimate net survival such as cause-specific survival and relative survival. The limitation of estimation of cause-specific survival particularly in India and the usefulness of relative survival are discussed. The various sources for estimating cancer survival are also discussed. As survival-estimates are to be projected on to the population at large, it becomes important to measure the variation of the estimates, and thus confidence intervals are used. Rothman′s confidence interval gives the most satisfactory result for survival estimate.

Death receptor pathways mediate targeted and non-targeted effects of ionizing radiations in breast cancer cells

International Nuclear Information System (INIS)

Luce, A.; Courtin, A.; Levalois, C.; Altmeyer-Morel, S.; Chevillard, S.; Lebeau, J.; Romeo, P.H.

2009-01-01

Delayed cell death by mitotic catastrophe is a frequent mode of solid tumor cell death after γ-irradiation, a widely used treatment of cancer. Whereas the mechanisms that underlie the early γ-irradiation-induced cell death are well documented, those that drive the delayed cell death are largely unknown. Here we show that the Fas, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and tumor necrosis factor (TNF)-α death receptor pathways mediate the delayed cell death observed after γ-irradiation of breast cancer cells. Early after irradiation, we observe the increased expression of Fas, TRAIL-R and TNF-R that first sensitizes cells to apoptosis. Later, the increased expression of FasL, TRAIL and TNF-α permit the apoptosis engagement linked to mitotic catastrophe. Treatments with TNF-α, TRAIL or anti-Fas antibody, early after radiation exposure, induce apoptosis, whereas the neutralization of the three death receptors pathways impairs the delayed cell death. We also show for the first time that irradiated breast cancer cells excrete soluble forms of the three ligands that can induce the death of sensitive bystander cells. Overall, these results define the molecular basis of the delayed cell death of irradiated cancer cells and identify the death receptors pathways as crucial actors in apoptosis induced by targeted as well as non-targeted effects of ionizing radiation. (authors)

A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients.

Science.gov (United States)

Habel, Laurel A; Shak, Steven; Jacobs, Marlena K; Capra, Angela; Alexander, Claire; Pho, Mylan; Baker, Joffre; Walker, Michael; Watson, Drew; Hackett, James; Blick, Noelle T; Greenberg, Deborah; Fehrenbacher, Louis; Langholz, Bryan; Quesenberry, Charles P

2006-01-01

The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting. A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score. After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7-3.9%), 10.7% (95% CI 6.3-14.9%), and 15.5% (95% CI 7.6-22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5-7.9%), 17.8% (95% CI 11.8-23.3%), and 19.9% (95% CI 14.2-25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values. In this large, population-based study of lymph

Changes in parents after the death of a child from cancer.

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Gilmer, Mary Jo; Foster, Terrah L; Vannatta, Kathryn; Barrera, Maru; Davies, Betty; Dietrich, Mary S; Fairclough, Diane L; Grollman, Jamie; Gerhardt, Cynthia A

2012-10-01

Few studies have compared multiple perspectives of changes experienced by parents after a child's death. This study used interviews with bereaved parents and siblings to examine changes in parents during the first year after the death of a child from cancer. Mothers (n=36), fathers (n=24), and siblings (n=39) from 40 families were recruited from three hospitals in the U.S. and Canada three to 12 months after the death (M=10.7, SD=3.5). Semistructured interviews with open-ended questions were conducted in the home with each participating parent and sibling separately. Content analysis identified emerging themes, and frequencies were compared between each paired set of reports (mother vs. sibling, father vs. sibling, and mother vs. father). Parents and siblings identified two major categories of change experienced by bereaved parents. These changes occurred in their personal lives (e.g., emotions, perspectives and priorities, physical state, work habits, coping/behaviors, spiritual beliefs, and feeling something is missing) and relationships (e.g., family, others). Ninety-four percent of the mothers, 87% of the fathers, and 69% of the siblings reported parental changes in at least one of these categories. Parents were more likely to report changes in priorities, whereas siblings reported more sadness in parents after the death. Positive and negative changes in parents after the death of a child from cancer occur in both personal and relational domains. Additional research is needed to determine the impact of a child's death on bereaved parents over time and to develop strategies to promote healthy adjustment. Copyright © 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Mechanism of neem limonoids-induced cell death in cancer: Role of oxidative phosphorylation.

Science.gov (United States)

Yadav, Neelu; Kumar, Sandeep; Kumar, Rahul; Srivastava, Pragya; Sun, Leimin; Rapali, Peter; Marlowe, Timothy; Schneider, Andrea; Inigo, Joseph R; O'Malley, Jordan; Londonkar, Ramesh; Gogada, Raghu; Chaudhary, Ajay K; Yadava, Nagendra; Chandra, Dhyan

2016-01-01

We have previously reported that neem limonoids (neem) induce multiple cancer cell death pathways. Here we dissect the underlying mechanisms of neem-induced apoptotic cell death in cancer. We observed that neem-induced caspase activation does not require Bax/Bak channel-mediated mitochondrial outer membrane permeabilization, permeability transition pore, and mitochondrial fragmentation. Neem enhanced mitochondrial DNA and mitochondrial biomass. While oxidative phosphorylation (OXPHOS) Complex-I activity was decreased, the activities of other OXPHOS complexes including Complex-II and -IV were unaltered. Increased reactive oxygen species (ROS) levels were associated with an increase in mitochondrial biomass and apoptosis upon neem exposure. Complex-I deficiency due to the loss of Ndufa1-encoded MWFE protein inhibited neem-induced caspase activation and apoptosis, but cell death induction was enhanced. Complex II-deficiency due to the loss of succinate dehydrogenase complex subunit C (SDHC) robustly decreased caspase activation, apoptosis, and cell death. Additionally, the ablation of Complexes-I, -III, -IV, and -V together did not inhibit caspase activation. Together, we demonstrate that neem limonoids target OXPHOS system to induce cancer cell death, which does not require upregulation or activation of proapoptotic Bcl-2 family proteins. Copyright © 2015 Elsevier Inc. All rights reserved.

IκBα mediates prostate cancer cell death induced by combinatorial targeting of the androgen receptor

International Nuclear Information System (INIS)

Carter, Sarah Louise; Centenera, Margaret Mary; Tilley, Wayne Desmond; Selth, Luke Ashton; Butler, Lisa Maree

2016-01-01

Combining different clinical agents to target multiple pathways in prostate cancer cells, including androgen receptor (AR) signaling, is potentially an effective strategy to improve outcomes for men with metastatic disease. We have previously demonstrated that sub-effective concentrations of an AR antagonist, bicalutamide, and the histone deacetylase inhibitor, vorinostat, act synergistically when combined to cause death of AR-dependent prostate cancer cells. In this study, expression profiling of human prostate cancer cells treated with bicalutamide or vorinostat, alone or in combination, was employed to determine the molecular mechanisms underlying this synergistic action. Cell viability assays and quantitative real time PCR were used to validate identified candidate genes. A substantial proportion of the genes modulated by the combination of bicalutamide and vorinostat were androgen regulated. Independent pathway analysis identified further pathways and genes, most notably NFKBIA (encoding IκBα, an inhibitor of NF-κB and p53 signaling), as targets of this combinatorial treatment. Depletion of IκBα by siRNA knockdown enhanced apoptosis of prostate cancer cells, while ectopic overexpression of IκBα markedly suppressed cell death induced by the combination of bicalutamide and vorinostat. These findings implicate IκBα as a key mediator of the apoptotic action of this combinatorial AR targeting strategy and a promising new therapeutic target for prostate cancer. The online version of this article (doi:10.1186/s12885-016-2188-2) contains supplementary material, which is available to authorized users

Changing patterns in place of cancer death in England: a population-based study.

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Wei Gao

Full Text Available Most patients with cancer prefer to die at home or in a hospice, but hospitals remain the most common place of death (PoD.This study aims to explore the changing time trends of PoD and the associated factors, which are essential for end-of-life care improvement.The study analysed all cancer deaths in England collected by the Office for National Statistics during 1993-2010 (n = 2,281,223. Time trends of age- and gender-standardised proportion of deaths in individual PoDs were evaluated using weighted piecewise linear regression. Variables associated with PoD (home or hospice versus hospital were determined using proportion ratio (PR derived from the log-binomial regression, adjusting for clustering effects. Hospital remained the most common PoD throughout the study period (48.0%; 95% CI 47.9%-48.0%, followed by home (24.5%; 95% CI 24.4%-24.5%, and hospice (16.4%; 95% CI 16.3%-16.4%. Home and hospice deaths increased since 2005 (0.87%; 95% CI 0.74%-0.99%/year, 0.24%; 95% CI 0.17%-0.32%/year, respectively, p<0.001, while hospital deaths declined (-1.20%; 95% CI -1.41 to -0.99/year, p<0.001. Patients who died from haematological cancer (PRs 0.46-0.52, who were single, widowed, or divorced (PRs 0.75-0.88, and aged over 75 (PRs 0.81-0.84 for 75-84; 0.66-0.72 for 85+ were less likely to die in home or hospice (p<0.001; reference groups: colorectal cancer, married, age 25-54. There was little improvement in patients with lung cancer of dying in home or hospice (PRs 0.87-0.88. Marital status became the second most important factor associated with PoD, after cancer type. Patients from less deprived areas (higher quintile of the deprivation index were more likely to die at home or in a hospice than those from more deprived areas (lower quintile of the deprivation index; PRs 1.02-1.12. The analysis is limited by a lack of data on individual patients' preferences for PoD or a clinical indication of the most appropriate PoD.More efforts are needed to reduce

Talking about death with children with incurable cancer: perspectives from parents.

NARCIS (Netherlands)

Geest, I.M.M. van der; Heuvel-Eibrink, M.M. van den; Vliet, L.M. van; Pluijm, S.M.F.; Streng, I.C.; Michiels, E.M.C.; Pieters, R.; Darlington A.S.E.

2015-01-01

Objective: To investigate the rationale and consequences associated with a parent's decision to discuss death with a child with incurable cancer. Study design: We present data from a larger retrospective study involving bereaved parents of a child who died of cancer. Parents were asked whether they

Perspectives on death and an afterlife in relation to quality of life, depression, and hopelessness in cancer patients without evidence of disease and advanced cancer patients.

Science.gov (United States)

van Laarhoven, Hanneke W M; Schilderman, Johannes; Verhagen, Constans A H H V M; Vissers, Kris C; Prins, Judith

2011-06-01

It is unknown whether cancer patients with different life expectancies have different attitudes and emotions toward death and an afterlife. Also, it is unclear whether these attitudes and emotions toward death and afterlife influence patients' distress. To assess the relationship of attitudes and emotions towards death and an afterlife with quality of life, depression and hopelessness in cancer patients without evidence of disease and advanced cancer patients facing death. Ninety-one cancer patients without evidence of disease and 57 advanced cancer patients completed the Dutch Attitudes Toward Death and Afterlife Scale. Emotions toward death were measured using the Self-Confrontation Method. Quality of life was measured with the Satisfaction with Life Scale and the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire. Depression and hopelessness were measured with the Beck Depression Inventory for Primary Care and the Beck Hopelessness Scale. Average scores on attitudes and emotions toward death and an afterlife were not significantly different between the two groups. However, in the no evidence of disease group, a negative association between negative emotions and social functioning was observed, which was not present in the advanced cancer group. In the advanced cancer group, associations were observed that were not present in the no evidence of disease group: positive associations between an explicitly religious attitude and global health status and between reincarnation belief and role and cognitive functioning, and a negative association between other-directed emotions and social functioning. Patients without evidence of disease and advanced cancer patients do not differ in attitudes or emotions toward death, but the relationship between these attitudes and emotions and aspects of quality of life varies. When there is no evidence of disease, negative emotions play the most important role, whereas in the advanced

Existential Concerns About Death

DEFF Research Database (Denmark)

Moestrup, Lene; Hansen, Helle Ploug

2015-01-01

psychology or Kübler-Ross’ theory about death stages. The complex concerns might be explained using Martin Heidegger’s phenomenological thinking. We aimed to illuminate dying patients´ existential concerns about the impending death through a descriptive analysis of semi-structured interviews with 17 cancer...... patients in Danish hospices. The main findings demonstrated how the patients faced the forthcoming death without being anxious of death but sorrowful about leaving life. Furthermore, patients expressed that they avoided thinking about death. However, some had reconstructed specific and positive ideas about...... afterlife and made accurate decisions for practical aspects of their death. The patients wished to focus on positive aspects in their daily life at hospice. It hereby seems important to have ongoing reflections and to include different theoretical perspectives when providing existential support to dying...

The calcimimetic R-568 induces apoptotic cell death in prostate cancer cells

Directory of Open Access Journals (Sweden)

Cheng Guangming

2009-07-01

Full Text Available Abstract Background Increased serum level of parathyroid hormone (PTH was found in metastatic prostate cancers. Calcimimetic R-568 was reported to reduce PTH expression, to suppress cell proliferation and to induce apoptosis in parathyroid cells. In this study, we investigated the effect of R-568 on cellular survival of prostate cancer cells. Methods Prostate cancer cell lines LNCaP and PC-3 were used in this study. Cellular survival was determined with MTT, trypan blue exclusion and fluorescent Live/Death assays. Western blot assay was utilized to assess apoptotic events induced by R-568 treatment. JC-1 staining was used to evaluate mitochondrial membrane potential. Results In cultured prostate cancer LNCaP and PC-3 cells, R-568 treatment significantly reduced cellular survival in a dose- and time-dependent manner. R-568-induced cell death was an apoptotic event, as evidenced by caspase-3 processing and PARP cleavage, as well as JC-1 color change in mitochondria. Knocking down calcium sensing receptor (CaSR significantly reduced R-568-induced cytotoxicity. Enforced expression of Bcl-xL gene abolished R-568-induced cell death, while loss of Bcl-xL expression led to increased cell death in R-568-treated LNCaP cells,. Conclusion Taken together, our data demonstrated that calcimimetic R-568 triggers an intrinsic mitochondria-related apoptotic pathway, which is dependent on the CaSR and is modulated by Bcl-xL anti-apoptotic pathway.

Anxiety, helplessness/hopelessness and 'desire for hastened death' in Korean cancer patients.

Science.gov (United States)

Shim, E-J; Hahm, B-J

2011-05-01

Despite a relatively high rate of suicide associated with cancer, this issue has not been explored in Korean patients. This study investigates the prevalence and factors related to 'the desire for hastened death' (DHD) in Korean cancer patients. A cross-sectional survey using standardised measures, including the Schedule of Attitudes toward Hastened Death and the Hospital Anxiety and Depression Scale, was performed with 131 patients with different types of cancer. 13.7% of the participants experienced moderate DHD (Schedule of Attitudes toward Hastened Death scores 5-9) and 1.7% experienced high DHD (≥10). Socio-demographic and disease-associated factors of the DHD included age, overall health and shortness of breath. The majority of psychosocial variables such as sadness, distress, 'helplessness/hopelessness' and 'anxious preoccupation' had a moderate association with DHD. Patients with a clinically significant level of anxiety or depression reported higher levels of DHD. Other significant correlates included 'meaning/peace', a sense of burdening family, dignity impairment and suicidal thoughts after diagnosis. Helplessness/hopelessness and anxiety were the strongest predictors of DHD in multivariate analysis. In view of significant role of helplessness/hopelessness and anxiety in the DHD of cancer patients, careful monitoring and management of these factors should be an integral part of cancer care to reduce the occurrence of DHD. © 2010 Blackwell Publishing Ltd.

Brain metastasis of breast cancer: clinical and radiologic findings

International Nuclear Information System (INIS)

An, Jin Kyung; Oh, Ki Keun; Kim, Eun Kyung; Chung, Tae Sub

2001-01-01

To analyse the clinical and radiologic findings brain metastasis of breast cancer. Sixty-one of 1399 patients in whom breast cancer was diagnosed between 1983 and 1999 were affected by brain metastasis. Among these 1399, the stage of the breast cancer, in descending order of frequency, was IIA (n=508), I (n=366), IIB (n=247), IIIA (n=189), IIIB (n=45), 0 (n=33) and IV (n=11). The stage of the 61 brain metastases, similarly ordered, was IIB (12.5%), IIA (3.9%), IIIA (3.1%), IIIB (2.2%) and I (0.8%). In all confirmed breast cancers, the age distribution, in descending order of frequency, was 40-49years (n=610), 50-59 (n=301), 30-39 (n=291), 60-69 (n=124), 20-19 (n=41), 70-79 (n=28), and 80-89 (n=4). The age distribution of brain metastasis was 20-29 (14.6%), 30-39 (7.9%), 50-59 (4.6%). 40-49 (2.6%) and 60-69 (1.6%). Imaging findings were available for 35 of the 61 patients affected by brain metastasis, and symptoms from brain among the 35, analysis of the symptoms of this metastasis, the site of the first distant metastasis to an extracranial or cranial organ, the interval from the diagnosis of breast cancer to brain metastasis, the interval from brain metastasis to death, and the difference in survival time between patients with initial and succeeding brain metastasis was undertaken. Brain CT findings were analysed in 29 cases and MRI findings in eight. The most common symptoms were headache and vomiting. Among the 35 brain metastasis patients for whom imaging findings were available, other systemic metastasis occurred in 22. Initial brain metastasis occurred in the remaining 13, and in seven of these there was also coincident organ metastasis, while six showed only brain metastasis, The most frequent intervals from the diagnosis of breast cancer to brain metastasis were 1-2 years(8/35) and 2-3years(8/35). Twenty-six of 35 patients died within one year of brain metastasis. Patients in whom this occurred later survived for longer than those in whom it occurred

Disparities in location of death of adolescents and young adults with cancer: A longitudinal, population study in California.

Science.gov (United States)

Rajeshuni, Nitya; Johnston, Emily E; Saynina, Olga; Sanders, Lee M; Chamberlain, Lisa J

2017-11-01

Patients with a terminal illness should have access to their chosen location of death. Cancer is the leading cause of non-accidental death among adolescents and young adults (AYAs; those aged 15-39 years). Although surveys have suggested that a majority of these patients prefer a home death, to the authors' knowledge, little is known regarding their barriers to accessing their preferred location of death. As a first step, the authors sought to determine, across a large population, 20-year trends in the location of death among AYA patients with cancer. Using the Vital Statistics Death Certificate Database of the California Office of Statewide Health Planning and Development, the authors performed a retrospective, population-based analysis of California patients with cancer aged 15 to 39 years who died between 1989 and 2011. Sociodemographic and clinical factors associated with hospital death were examined using multivariable logistic regression. Of 30,573 AYA oncology decedents, 57% died in a hospital, 33% died at home, and 10% died in other locations (eg, hospice facility or nursing facility). Between 1989 and 1994, hospital death rates decreased from 68.3% to 53.6% and at-home death rates increased from 16.8% to 35.5%. Between 1995 and 2011, these rates were stable. Those individuals who were more likely to die in a hospital were those aged deaths occurred in a hospital, with a 5-year shift to more in-home deaths that abated after 1995. In-hospital deaths were more common among younger patients, patients of minority race/ethnicities, and those with a leukemia or lymphoma diagnosis. Further study is needed to determine whether these rates and disparities are consistent with patient preferences. Cancer 2017;123:4178-4184. © 2017 American Cancer Society. © 2017 American Cancer Society.

Sigma-2 ligands and PARP inhibitors synergistically trigger cell death in breast cancer cells

International Nuclear Information System (INIS)

McDonald, Elizabeth S.; Mankoff, Julia; Makvandi, Mehran; Chu, Wenhua; Chu, Yunxiang; Mach, Robert H.; Zeng, Chenbo

2017-01-01

The sigma-2 receptor is overexpressed in proliferating cells compared to quiescent cells and has been used as a target for imaging solid tumors by positron emission tomography. Recent work has suggested that the sigma-2 receptor may also be an effective therapeutic target for cancer therapy. Poly (ADP-ribose) polymerase (PARP) is a family of enzymes involved in DNA damage response. In this study, we looked for potential synergy of cytotoxicity between PARP inhibitors and sigma-2 receptor ligands in breast cancer cell lines. We showed that the PARP inhibitor, YUN3-6, sensitized mouse breast cancer cell line, EMT6, to sigma-2 receptor ligand (SV119, WC-26, and RHM-138) induced cell death determined by cell viability assay and colony forming assay. The PARP inhibitor, olaparib, sensitized tumor cells to a different sigma-2 receptor ligand SW43-induced apoptosis and cell death in human triple negative cell line, MDA-MB-231. Olaparib inhibited PARP activity and cell proliferation, and arrested cells in G2/M phase of the cell cycle in MDA-MB-231 cells. Subsequently cells became sensitized to SW43 induced cell death. In conclusion, the combination of sigma-2 receptor ligands and PARP inhibitors appears to hold promise for synergistically triggering cell death in certain types of breast cancer cells and merits further investigation. - Highlights: • PARPi, YUN3-6 and olaparib, and σ2 ligands, SV119 and SW43, were evaluated. • Mouse and human breast cancer cells, EMT6 and MDA-MB-231 respectively, were used. • YUN3-6 and SV119 synergistically triggered cell death in EMT6 cells. • Olaparib and SW43 additively triggered cell death in MDA-MB-231 cells. • Olaparib arrested cells in G2/M in MDA-MB-231 cells.

Breast cancer patients with dense breasts do not have increased death risk

Science.gov (United States)

High mammographic breast density, which is a marker of increased risk of developing breast cancer, does not seem to increase the risk of death among breast cancer patients, according to a study led by Gretchen L. Gierach, Ph.D., NCI. Image shows physician

Using the National Death Index to Identify Duplicate Cancer Incident Cases in Florida and New York, 1996–2005

Science.gov (United States)

Wohler, Brad; Qiao, Baozhen; MacKinnon, Jill A.; Schymura, Maria J.

2014-01-01

Introduction Cancer registries link incidence data to state death certificates to update vital status and identify missing cases; they also link these data to the National Death Index (NDI) to update vital status among patients who leave the state after their diagnosis. This study explored the use of information from NDI linkages to identify potential duplicate cancer cases registered in both Florida and New York. Methods The Florida Cancer Data System (FCDS) and the New York State Cancer Registry (NYSCR) linked incidence data with state and NDI death records from 1996 through 2005. Information for patients whose death occurred in the reciprocal state (the death state) was exchanged. Potential duplicate cases were those that had the same diagnosis and the same or similar diagnosis date. Results NDI identified 4,657 FCDS cancer patients who died in New York and 2,740 NYSCR cancer patients who died in Florida. Matching identified 5,030 cases registered in both states; 508 were death certificate-only (DCO) cases in the death state’s registry, and 3,760 (74.8%) were potential duplicates. Among FCDS and NYSCR patients who died and were registered in the registry of the reciprocal state, more than 50% were registered with the same cancer diagnosis, and approximately 80% had similar diagnosis dates (within 1 year). Conclusion NDI identified DCO cases in the death state’s cancer registry and a large proportion of potential duplicate cases. Standards are needed for assigning primary residence when multiple registries report the same case. The registry initiating the NDI linkage should consider sharing relevant information with death state registries so that these registries can remove erroneous DCO cases from their databases. PMID:25254985

Human colon cancer HT-29 cell death responses to doxorubicin and Morus Alba leaves flavonoid extract.

Science.gov (United States)

Fallah, S; Karimi, A; Panahi, G; Gerayesh Nejad, S; Fadaei, R; Seifi, M

2016-03-31

The mechanistic basis for the biological properties of Morus alba flavonoid extract (MFE) and chemotherapy drug of doxorubicin on human colon cancer HT-29 cell line death are unknown. The effect of doxorubicin and flavonoid extract on colon cancer HT-29 cell line death and identification of APC gene expression and PARP concentration of HT-29 cell line were investigated. The results showed that flavonoid extract and doxorubicin induce a dose dependent cell death in HT-29 cell line. MFE and doxorubicin exert a cytotoxic effect on human colon cancer HT-29 cell line by probably promoting or induction of apoptosis.

An Ursolic Acid Derived Small Molecule Triggers Cancer Cell Death through Hyperstimulation of Macropinocytosis.

Science.gov (United States)

Sun, Lin; Li, Bin; Su, Xiaohui; Chen, Ge; Li, Yaqin; Yu, Linqian; Li, Li; Wei, Wanguo

2017-08-10

Macropinocytosis is a transient endocytosis that internalizes extracellular fluid and particles into vacuoles. Recent studies suggest that hyperstimulation of macropinocytosis can induce a novel nonapoptotic cell death, methuosis. In this report, we describe the identification of an ursolic acid derived small molecule (compound 17), which induces cancer cell death through hyperstimulation of macropinocytosis. 17 causes the accumulation of vacuoles derived from macropinosomes based on transmission electron microscopy, time-lapse microscopy, and labeling with extracellular fluid phase tracers. The vacuoles induced by 17 separate from other cytoplasmic compartments but acquire some characteristics of late endosomes and lysosomes. Inhibiting hyperstimulation of macropinocytosis with the specific inhibitor amiloride blocks cell death, implicating that 17 leads to cell death via macropinocytosis, which is coincident with methuosis. Our results uncovered a novel cell death pathway involved in the activity of 17, which may provide a basis for further development of natural-product-derived scaffolds for drugs that trigger cancer cell death by methuosis.

Cardiorespiratory fitness and death from cancer: a 42-year follow-up from the Copenhagen Male Study.

Science.gov (United States)

Jensen, Magnus Thorsten; Holtermann, Andreas; Bay, Hans; Gyntelberg, Finn

2017-09-01

Poor cardiorespiratory fitness (CRF) is associated with death from cancer. If follow-up time is short, this association may be confounded by subclinical disease already present at the time of CRF assessment. This study investigates the association between CRF and death from cancer and any cause with 42 years and 44 years of follow-up, respectively. Middle-aged, employed and cancer-free Danish men from the prospective Copenhagen Male Study , enrolled in 1970-1971, were included. CRF (maximal oxygen consumption (VO 2 max)) was estimated using a bicycle ergometer test and analysed in multivariable Cox models including conventional risk factors, social class and self-reported physical activity. Death from cancer and all-cause mortality was assessed using Danish national registers. Follow-up was 100% complete. In total, 5131 men were included, mean (SD) age 48.8 (5.4) years. During 44 years of follow-up, 4486 subjects died (87.4%), 1527 (29.8%) from cancer. In multivariable models, CRF was highly significantly inversely associated with death from cancer and all-cause mortality ((HR (95% CI)) 0.83 (0.77 to 0.90) and 0.89 (0.85 to 0.93) per 10 mL/kg/min increase in estimated VO 2 max, respectively). A similar association was seen across specific cancer groups, except death from prostate cancer (1.00 (0.82 to 1.2); p=0.97; n=231). The associations between CRF and outcomes remained essentially unchanged after excluding subjects dying within 10 years (n=377) and 20 years (n=1276) of inclusion. CRF is highly significantly inversely associated with death from cancer and all-cause mortality. The associations are robust for exclusion of subjects dying within 20 years of study inclusion, thereby suggesting a minimal influence of reverse causation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Risk of death from cardiovascular disease following breast cancer : a systematic review

NARCIS (Netherlands)

Gernaat, S. A.M.; Ho, P. J.; Rijnberg, N.; Emaus, M. J.; Baak, L. M.; Hartman, M.; Grobbee, D. E.; Verkooijen, H. M.

Purpose: Breast cancer incidence and survival is high, which results in high prevalence of breast cancer survivors. The risk of (death from) cardiovascular disease (CVD) is higher in patients exposed to cardiotoxic treatments, in particular if they have pre-existing CVD risk factors. This study

Magnesium in drinking water modifies the association between nitrate ingestion and risk of death from esophageal cancer.

Science.gov (United States)

Liao, Yen-Hsiung; Chen, Pei-Shih; Chiu, Hui-Fen; Yang, Chun-Yuh

2013-01-01

The objective of this study was to explore whether magnesium (Mg) levels in drinking water modified the effects of nitrate on esophageal cancer risk occurrence. A matched cancer case-control study was used to investigate the relationship between the risk of death from esophageal cancer and exposure to nitrate in drinking water in Taiwan. All esophageal cancer deaths of Taiwan residents from 2006 through 2010 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO(3)-N) and Mg in drinking water were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO(3)-N and Mg exposure via drinking water. Evidence of an interaction was noted between drinking water NO(3)-N and Mg intake. This is the first study to report effect modification by Mg intake originating from drinking water on an association between NO(3)-N exposure and increased risk mortality attributed to esophageal cancer.

Years of Life and Productivity Loss from Potentially Avoidable Colorectal Cancer Deaths in U.S. Counties with Lower Educational Attainment (2008-2012).

Science.gov (United States)

Weir, Hannah K; Li, Chunyu; Henley, S Jane; Joseph, Djenaba

2017-05-01

Background: Educational attainment (EA) is inversely associated with colorectal cancer risk. Colorectal cancer screening can save lives if precancerous polyps or early cancers are found and successfully treated. This study aims to estimate the potential productivity loss (PPL) and associated avoidable colorectal cancer-related deaths among screen-eligible adults residing in lower EA counties in the United States. Methods: Mortality and population data were used to examine colorectal cancer deaths (2008-2012) among adults aged 50 to 74 years in lower EA counties, and to estimate the expected number of deaths using the mortality experience from high EA counties. Excess deaths (observed-expected) were used to estimate potential years life lost, and the human capital method was used to estimate PPL in 2012 U.S. dollars. Results: County-level colorectal cancer death rates were inversely associated with county-level EA. Of the 100,857 colorectal cancer deaths in lower EA counties, we estimated that more than 21,000 (1 in 5) was potentially avoidable and resulted in nearly $2 billion annual productivity loss. Conclusions: County-level EA disparities contribute to a large number of potentially avoidable colorectal cancer-related deaths. Increased prevention and improved screening potentially could decrease deaths and help reduce the associated economic burden in lower EA communities. Increased screening could further reduce deaths in all EA groups. Impact: These results estimate the large economic impact of potentially avoidable colorectal cancer-related deaths in economically disadvantaged communities, as measured by lower EA. Cancer Epidemiol Biomarkers Prev; 26(5); 736-42. ©2016 AACR . ©2016 American Association for Cancer Research.

Targeting death receptors to fight cancer: from biological rational to clinical implementation.

Science.gov (United States)

Mocellin, S

2010-01-01

Considering that most currently available chemotherapeutic drugs work by inducing cell apoptosis, it is not surprising that many expectations in cancer research come from the therapeutic exploitation of the naturally occurring death pathways. Receptor mediated apoptosis depends upon the engagement of specific ligands with their respective membrane receptors and - within the frame of complex regulatory networks - modulates some key physiological and pathological processes such as lymphocyte survival, inflammation and infectious diseases. A pivotal observation was that some of these pathways may be over activated in cancer under particular circumstances, which opened the avenue for tumor-specific therapeutic interventions. Although one death-related ligand (e.g., tumor necrosis factor, TNF) is currently the basis of effective anticancer regimens in the clinical setting, the systemic toxicity is hampering its wide therapeutic exploitation. However, strategies to split the therapeutic from the toxic TNF activity are being devised. Furthermore, other death receptor pathways (e.g., Fas/FasL, TRAIL/TRAIL receptor) are being intensively investigated in order to therapeutically exploit their activity against cancer. This article summarizes the current knowledge on the molecular features of death receptor pathways that make them an attractive target for anticancer therapeutics. In addition, the results so far obtained in the clinical oncology setting as well as the issues to be faced while interfering with these pathways for therapeutic purposes will be overviewed.

Mulberry anthocyanins improves thyroid cancer progression mainly by inducing apoptosis and autophagy cell death

Directory of Open Access Journals (Sweden)

Hou-Long Long

2018-05-01

Full Text Available Dietary anthocyanin compounds have multiple biological effects, including antioxidant, anti-inflammatory, and anti-atherosclerotic characteristics. The present study evaluated the anti-tumor capacity of mulberry anthocyanins (MA in thyroid cancer cells. Our data showed that MA suppressed SW1736 and HTh-7 cell proliferation in a time- and dose-dependent manner. Meanwhile, flow cytometry results indicated that MA significantly increased SW1736 and HTh-7 cell apoptosis. We additionally observed that SW1736 and HTh-7 cell autophagy was markedly enhanced after MA treatment. Importantly, anthocyanin-induced cell death was largely abolished by 3-methyladenine (3-MA or chloroquine diphosphate salt (CQ treatment, suggesting that MA-induced SW1736 and HTh-7 cell death was partially dependent on autophagy. In addition, activation of protein kinase B (Akt, mammalian target of rapamycin (mTOR, and ribosomal protein S6 (S6 were significantly suppressed by anthocyanin exposure. In summary, MA may serve as an adjunctive therapy for thyroid cancer patients through induction of apoptosis and autophagy-dependent cell death. Keywords: Mulberry anthocyanins, Thyroid cancer, Apoptosis, Autophagic death

Spiritual Well-being May Reduce the Negative Impacts of Cancer Symptoms on the Quality of Life and the Desire for Hastened Death in Terminally Ill Cancer Patients.

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Wang, Yin-Chih; Lin, Chia-Chin

2016-01-01

Spirituality is a central component of the well-being of terminally ill cancer patients. The aim of this study was to examine the mediating or moderating role of spiritual well-being in reducing the impact of cancer-related symptoms on quality of life and the desire for hastened death in terminally ill cancer patients. Eighty-five terminally ill cancer patients were assessed using the Taiwanese version of the M. D. Anderson Symptom Inventory, the Functional Assessment of Cancer Therapy-General, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being, the Beck Hopelessness Scale, and the Schedule of Attitudes Toward Hastened Death. Spiritual well-being was significantly negatively correlated with symptom severity (r = -0.46, P quality of life (r = -0.54) and positively correlated with hopelessness (r = 0.51, P quality of life. Spiritual well-being was a partial mediator between symptom severity and the desire for hastened death. The meaning subscale of spiritual well-being was a more significant predictor of the desire for hastened death and quality of life than the faith subscale was. Spiritual well-being may reduce the negative impacts of cancer on quality of life and the desire for hastened death. Appropriate spiritual care may reduce the negative impact of severe cancer symptoms on quality of life and the desire for hastened death in terminally ill cancer patients.

In Situ Gelation-Induced Death of Cancer Cells Based on Proteinosomes.

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Zhou, Yuting; Song, Jianmin; Wang, Lei; Xue, Xuting; Liu, Xiaoman; Xie, Hui; Huang, Xin

2017-08-14

Hydrogels are an excellent type of material that can be utilized as a platform for cell culture. However, when a bulky hydrogel forms on the inside of cancer cells, the result would be different. In this study, we demonstrate a method for in situ gelation inside cancer cells that can efficiently induce cell death. Glutathione-responsive proteinosomes with good biocompatibility were prepared as carriers for sodium alginate to be endocytosed by cancer cells, where the chelation between sodium alginate and free calcium ions in the culture medium occurs during the diffusion process. The uptake of the hydrogel-loaded proteinosomes into the cancer cells, and then the triggered release of hydrogel with concomitant aggregation, was well-confirmed by monitoring the change of the Young's modulus of the cells based on AFM force measurements. Accordingly, when a large amount of hydrogel formed in cells, the cell viability would be inhibited by ∼90% by MTT assay at a concentration of 5.0 μM of hydrogel-loaded proteinosomes after 48 h incubation, which clearly proves the feasibility of the demonstrated method for killing cancer cells. Although more details regarding the mechanism of cell death should be conducted in the near future, such a demonstrated method of in situ gelation inside cells provides another choice for killing cancer cells.

Nitrate in drinking water and risk of death from bladder cancer: an ecological case-control study in Taiwan.

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Chiu, Hui-Fen; Tsai, Shang-Shyue; Yang, Chun-Yuh

2007-06-01

The relationship between nitrate levels in drinking water and bladder cancer development is controversial. A matched cancer case-control with nitrate ecology study was used to investigate the association between bladder cancer mortality occurrence and nitrate exposure from Taiwan drinking water. All bladder cancer deaths of Taiwan residents from 1999 through 2003 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth,and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on nitrate-nitrogen (NO3-N) levels in drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios for bladder cancer death for those with high nitrate levels in their drinking water were 1.76 (1.28-2.42) and 1.96 (1.41-2.72) as compared to the lowest tertile. The results of the present study show that there was a significant positive relationship between the levels of nitrate in drinking water and risk of death from bladder cancer.

Snake venom toxin from vipera lebetina turanica induces apoptosis of colon cancer cells via upregulation of ROS- and JNK-mediated death receptor expression

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Park, Mi Hee; Jo, MiRan; Won, Dohee; Song, Ho Sueb; Han, Sang Bae; Song, Min Jong; Hong, Jin Tae

2012-01-01

Abundant research suggested that the cancer cells avoid destruction by the immune system through down-regulation or mutation of death receptors. Therefore, it is very important that finding the agents that increase the death receptors of cancer cells. In this study, we demonstrated that the snake venom toxin from Vipera lebetina turanica induce the apoptosis of colon cancer cells through reactive oxygen species (ROS) and c-Jun N-terminal kinases (JNK) dependent death receptor (DR4 and DR5) expression. We used cell viability assays, DAPI/TUNEL assays, as well as western blot for detection of apoptosis related proteins and DRs to demonstrate that snake venom toxin-induced apoptosis is DR4 and DR5 dependent. We carried out transient siRNA knockdowns of DR4 and DR5 in colon cancer cells. We showed that snake venom toxin inhibited growth of colon cancer cells through induction of apoptosis. We also showed that the expression of DR4 and DR5 was increased by treatment of snake venom toxin. Moreover, knockdown of DR4 or DR5 reversed the effect of snake venom toxin. Snake venom toxin also induced JNK phosphorylation and ROS generation, however, pretreatment of JNK inhibitor and ROS scavenger reversed the inhibitory effect of snake venom toxin on cancer cell proliferation, and reduced the snake venom toxin-induced upregulation of DR4 and DR5 expression. Our results indicated that snake venom toxin could inhibit human colon cancer cell growth, and these effects may be related to ROS and JNK mediated activation of death receptor (DR4 and DR5) signals

Nitrates in drinking water and the risk of death from brain cancer: does hardness in drinking water matter?

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Ho, Chi-Kung; Yang, Ya-Hui; Yang, Chun-Yuh

2011-01-01

The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and risk of death from brain cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the influence of nitrates on development of brain cancer. A matched cancer case-control study was used to investigate the relationship between the risk of death from brain cancer and exposure to nitrates in drinking water in Taiwan. All brain cancer deaths of Taiwan residents from 2003 through 2008 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO₃-N), Ca, and Mg in drinking water was obtained from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO₃-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO₃-N exposure level was cancer occurrence was 1.04 (0.85-1.27) for individuals who resided in municipalities served by drinking water with a NO₃-N exposure ≥ 0.38 ppm. No marked effect modification was observed due to Ca and Mg intake via drinking water on brain cancer occurrence.

Apoptotic Cell Death Induced by Resveratrol Is Partially Mediated by the Autophagy Pathway in Human Ovarian Cancer Cells.

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Fangfang Lang

Full Text Available Resveratrol (trans-3,4,5'-trihydroxystilbene is an active compound in food, such as red grapes, peanuts, and berries. Resveratrol exhibits an anticancer effect on various human cancer cells. However, the mechanism of resveratrol-induced anti-cancer effect at the molecular level remains to be elucidated. In this study, the mechanism underlying the anti-cancer effect of resveratrol in human ovarian cancer cells (OVCAR-3 and Caov-3 was investigated using various molecular biology techniques, such as flow cytometry, western blotting, and RNA interference, with a major focus on the potential role of autophagy in resveratrol-induced apoptotic cell death. We demonstrated that resveratrol induced reactive oxygen species (ROS generation, which triggers autophagy and subsequent apoptotic cell death. Resveratrol induced ATG5 expression and promoted LC3 cleavage. The apoptotic cell death induced by resveratrol was attenuated by both pharmacological and genetic inhibition of autophagy. The autophagy inhibitor chloroquine, which functions at the late stage of autophagy, significantly reduced resveratrol-induced cell death and caspase 3 activity in human ovarian cancer cells. We also demonstrated that targeting ATG5 by siRNA also suppressed resveratrol-induced apoptotic cell death. Thus, we concluded that a common pathway between autophagy and apoptosis exists in resveratrol-induced cell death in OVCAR-3 human ovarian cancer cells.

Repeated assessments of symptom severity improve predictions for risk of death among patients with cancer.

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Sutradhar, Rinku; Atzema, Clare; Seow, Hsien; Earle, Craig; Porter, Joan; Barbera, Lisa

2014-12-01

Although prior studies show the importance of self-reported symptom scores as predictors of cancer survival, most are based on scores recorded at a single point in time. To show that information on repeated assessments of symptom severity improves predictions for risk of death and to use updated symptom information for determining whether worsening of symptom scores is associated with a higher hazard of death. This was a province-based longitudinal study of adult outpatients who had a cancer diagnosis and had assessments of symptom severity. We implemented a time-to-death Cox model with a time-varying covariate for each symptom to account for changing symptom scores over time. This model was compared with that using only a time-fixed (baseline) covariate for each symptom. The regression coefficients of each model were derived based on a randomly selected 60% of patients, and then, the predictive performance of each model was assessed via concordance probabilities when applied to the remaining 40% of patients. This study had 66,112 patients diagnosed with cancer and more than 310,000 assessments of symptoms. The use of repeated assessments of symptom scores improved predictions for risk of death compared with using only baseline symptom scores. Increased pain and fatigue and reduced appetite were the strongest predictors for death. If available, researchers should consider including changing information on symptom scores, as opposed to only baseline information on symptom scores, when examining hazard of death among patients with cancer. Worsening of pain, fatigue, and appetite may be a flag for impending death. Copyright © 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Potentially preventable infant and child deaths identified at autopsy; findings and implications.

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Bamber, Andrew R; Mifsud, William; Wolfe, Ingrid; Cass, Hilary; Pryce, Jeremy; Malone, Marian; Sebire, Neil J

2015-09-01

The purpose of the study was to determine the proportion of pediatric deaths investigated by HM Coronial autopsy which were potentially preventable deaths due to treatable natural disease, and what implications such findings may have for health policies to reduce their occurrence. A retrospective study of 1779 autopsies of individuals between 7 days and 14 years of age requested by HM Coroner, taking place in one specialist pediatric autopsy center, was undertaken. Cases were included if they involved a definite natural disease process in which appropriate recognition and treatment was likely to have affected their outcome. Strict criteria were used and cases were excluded where the individual had any longstanding condition which might have predisposed them to, or altered the recognition of, acute illness, or its response to therapy. Almost 8% (134/1779) of the study group were potentially preventable deaths as a result of natural disease, the majority occurring in children younger than 2 years of age. Most individuals reported between 1 and 7 days of symptoms before their death, and the majority had sought medical advice during this period, including from general practitioners within working hours, and hospital emergency departments. Of those who had sought medical attention, around one-third had done so more than once (28%, 15/53). Sepsis and pneumonia accounted for the majority of deaths (46 and 34% respectively), with all infections (sepsis, pneumonia and meningitis) accounting for 110/134 (82%). Around 10% of pediatric deaths referred to HM Coroner are potentially preventable, being the result of treatable natural acute illnesses. In many cases medical advice had been sought during the final illness. The results highlight how a review of autopsy data can identify significant findings with the potential to reduce mortality, and the importance of centralized investigation and reporting of pediatric deaths.

Cancer-selective death of human breast cancer cells by leelamine is mediated by bax and bak activation.

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Sehrawat, Anuradha; Kim, Su-Hyeong; Hahm, Eun-Ryeong; Arlotti, Julie A; Eiseman, Julie; Shiva, Sruti S; Rigatti, Lora H; Singh, Shivendra V

2017-02-01

The present study is the first to report inhibition of breast cancer cell growth in vitro and in vivo and suppression of self-renewal of breast cancer stem cells (bCSC) by a pine bark component (leelamine). Except for a few recent publications in melanoma, anticancer pharmacology of this interesting phytochemical is largely elusive. Leelamine (LLM) dose-dependently inhibited viability of MDA-MB-231 (triple-negative), MCF-7 (estrogen receptor-positive), and SUM159 (triple-negative) human breast cancer cells in association with apoptotic cell death induction. To the contrary, a normal mammary epithelial cell line derived from fibrocystic breast disease and spontaneously immortalized (MCF-10A) was fully resistant to LLM-mediated cell growth inhibition and apoptosis induction. LLM also inhibited self-renewal of breast cancer stem cells. Apoptosis induction by LLM in breast cancer cells was accompanied by a modest increase in reactive oxygen species production, which was not due to inhibition of mitochondrial electron transport chain complexes. Nevertheless, ectopic expression of manganese superoxide dismutase conferred partial protection against LLM-induced cell death but only at a lower yet pharmacologically relevant concentration. Exposure of breast cancer cells to LLM resulted in (a) induction and/or activation of multidomain proapoptotic proteins Bax and Bak, (b) caspase-9 activation, and (c) cytosolic release of cytochrome c. Bax and Bak deficiency in immortalized fibroblasts conferred significant protection against cell death by LLM. Intraperitoneal administration of LLM (7.5 mg/kg; 5 times/wk) suppressed the growth of orthotopic SUM159 xenografts in mice without any toxicity. In conclusion, the present study provides critical preclinical data to warrant further investigation of LLM. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Find an NCI-Designated Cancer Center

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Find the locations of NCI-designated cancer centers by area, region, state, or name that includes contact information to help health care providers and cancer patients with referrals to clinical trials.

Patterns in place of cancer death in the State of Qatar: a population-based study.

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Hassan Mohsen

Full Text Available BACKGROUND: International studies show that most people prefer to die at home; however, hospitals remain the most common place of death (PoD. This study aims to investigate the patterns in PoD and the associated factors, which are crucial for end-of-life cancer care enhancement. METHOD: This retrospective, population-based study analyzed all registered cancer deaths in Qatar between January 1, 2006 and December 31, 2012 (n = 1,224. The main outcome measures were patient characteristics: age, gender, nationality, cancer diagnosis, year of death, and PoD. Time trends for age-standardized proportions of death in individual PoDs were evaluated using chi-square analysis. Odds ratio (OR were determined for variables associated with the most preferred (acute palliative care unit [APCU] and hematology/oncology ward versus least preferred (ICU and general medicine ward PoDs in Qatar, stratified by nationality. RESULTS: The hematology/oncology ward was the most common PoD (32.4%; 95% CI 26.7-35.3% followed by ICU (31.4%; 95% CI 28.7-34.3%, APCU (26.9%; 95% CI 24.3-29.6%, and general medicine ward (9.2%; 95% CI 7.6-11.1%. APCU trended upward (+0.057/year; p<0.001, while the hematology/oncology ward trended downward (-0.055/year; p<0.001. No statistically significant changes occurred in the other PoDs; home deaths remained low (0.4%; 95% Cl 0.38-0.42. Qataris who died from liver cancer (OR 0.23 and aged 65 or older (OR 0.64 were less likely to die in the APCU or hematology/oncology ward (p<0.05. Non-Qataris who died from pancreatic cancer (OR 3.12 and female (OR 2.05 were more likely to die in the APCU or hematology/oncology ward (p<0.05. Both Qataris and non-Qataris who died from hematologic malignancy (OR 0.18 and 0.41, respectively were more likely to die in the ICU or general medicine ward (p<0.05. CONCLUSION: A high percentage of cancer deaths in Qatar occur in hospital. As home was the preferred PoD for most people, effective home care and hospice

Induction of Immunogenic Cell Death with Non-Thermal Plasma for Cancer Immunotherapy

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Lin, Abraham G.

Even with the recent advancements in cancer immunotherapy, treatments are still associated with debilitating side effects and unacceptable fail rates. Induction of immunogenic cell death (ICD) in tumors is a promising approach to cancer treatment that may overcome these deficiencies. Cells undergoing ICD pathways enhance the interactions between cancerous cells and immune cells of the patient, resulting in the generation of anti-cancer immunity. The goal of this therapy relies on the engagement and reestablishment of the patient's natural immune processes to target and eliminate cancerous cells systemically. The main objective of this research was to determine if non-thermal plasma could be used to elicit immunogenic cancer cell death for cancer immunotherapy. My hypothesis was that plasma induces immunogenic cancer cell death through oxidative stress pathways, followed by development of a specific anti-tumor immune response. This was tested by investigating the interactions between plasma and multiple cancerous cells in vitro and validating anti-tumor immune responses in vivo. Following plasma treatment, two surrogate ICD markers, secreted adenosine triphosphate (ATP) and surface exposed calreticulin (ecto-CRT), were emitted from all three cancerous cell lines tested: A549 lung carcinoma cell line, CNE-1 radiation-resistant nasopharyngeal cell line and CT26 colorectal cancer cell line. When these cells were co-cultured with macrophages, cells of the innate immune system, the tumoricidal activity of macrophages was enhanced, thus demonstrating the immunostimulatory activity of cells undergoing ICD. The underlying mechanisms of plasma-induced ICD were also evaluated. When plasma is generated, four major components are produced: electromagnetic fields, ultraviolet radiation, and charged and neutral reactive species. Of these, we determined that plasma-generated charged and short-lived reactive oxygen species (ROS) were the major effectors of ICD. Following plasma

Death-associated protein kinase (DAPK) and signal transduction: regulation in cancer.

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Michie, Alison M; McCaig, Alison M; Nakagawa, Rinako; Vukovic, Milica

2010-01-01

Death-associated protein kinase (DAPK) is a pro-apoptotic serine/threonine protein kinase that is dysregulated in a wide variety of cancers. The mechanism by which this occurs has largely been attributed to promoter hypermethylation, which results in gene silencing. However, recent studies indicate that DAPK expression can be detected in some cancers, but its function is still repressed, suggesting that DAPK activity can be subverted at a post-translational level in cancer cells. This review will focus on recent data describing potential mechanisms that may alter the expression, regulation or function of DAPK.

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

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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.

Death by suicide and other externally caused injuries following a cancer diagnosis: the Japan Public Health Center-based Prospective Study.

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Yamauchi, Takashi; Inagaki, Masatoshi; Yonemoto, Naohiro; Iwasaki, Motoki; Inoue, Manami; Akechi, Tatsuo; Iso, Hiroyasu; Tsugane, Shoichiro

2014-09-01

There have been very few population-based prospective studies that have investigated the risks of deaths by suicide and other externally caused injuries (ECIs) among cancer patients in an Asian population. This study investigated whether the risk of death by both suicide and ECIs increases during the first year following the initial diagnosis of cancer. Data were analyzed from a population-based cohort of Japanese residents between 1990 and 2010, collected during the Japan Public Health Center-based Prospective Study. Poisson regression models were used to calculate adjusted risk ratios (RRs) for both suicide and ECI deaths. To adjust for unmeasured confounding factors, case-crossover analyses were conducted for all patients with cancer who died by suicide and ECIs. A population-based cohort of 102,843 Japanese residents was established. During the follow-up period, there were 34 suicides and 48 ECI deaths among patients with cancer, as compared with 527 suicides and 707 ECI deaths among those who did not have cancer. Analyses revealed that those who were newly diagnosed with cancer were at a greatly increased risk of death by suicide and ECIs within the first year after their diagnosis (suicide RR = 23.9, 95% CI: 13.8-41.6; ECI RR = 18.8, 95% CI: 11.4-31.0). Furthermore, the case-crossover analyses generally confirmed the results of the Poisson regressions. The risks of suicide and ECI deaths within the first year after a cancer diagnosis were higher than those among cancer-free populations. A diagnosis of cancer is a critical experience that may increase the risk of fatal outcomes. Copyright © 2014 John Wiley & Sons, Ltd.

Haloperidol and sudden cardiac death in dementia: autopsy findings in psychiatric inpatients.

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Ifteni, Petru; Grudnikoff, Eugene; Koppel, Jeremy; Kremen, Neil; Correll, Christoph U; Kane, John M; Manu, Peter

2015-12-01

Treatment with haloperidol has been shown, in studies using death certificates and prescription files, to be associated with an excess of sudden cardiac deaths, and regulatory warnings highlight this risk in patients with dementia. We used autopsy findings to determine whether the rate of sudden cardiac death is greater in cases of unexpected deaths of patients with dementia treated with haloperidol. From 1989 through 2013, 1219 patients with a primary diagnosis of dementia with behavioral disturbance were admitted to a psychiatric hospital, and 65 (5.3%) died suddenly. Sixty-five patients (5.3%) died unexpectedly. Complete post-mortem examinations after the sudden death were performed in 55 (84.6%) patients. Twenty-seven of the autopsied cases (49.1%) had been treated with haloperidol orally (2.2 mg ± 2.1 mg/day), the only antipsychotic used in this cohort. Univariable comparisons and multivariable regression analyses compared the groups of patients with or without sudden cardiac death. The leading causes of death were sudden cardiac death (32.7%), myocardial infarction (25.5% of patients), pneumonia (23.6%), and stroke (10.9%). Patients with sudden cardiac death and those with anatomically established cause of death were similar regarding the use of haloperidol (p = 0.5). Sudden cardiac death patients were more likely to suffer from Alzheimer's dementia (p = 0.027) and to have a past history of heart disease (p = 0.0094), and less likely to have been treated with a mood stabilizer (p = 0.024), but none of these variables were independent predictors of sudden cardiac death. Autopsy data suggest that oral haloperidol is not associated with increased risk of sudden cardiac death in psychiatric inpatients with dementia. Copyright © 2015 John Wiley & Sons, Ltd.

Intracellular Hyper-Acidification Potentiated by Hydrogen Sulfide Mediates Invasive and Therapy Resistant Cancer Cell Death

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Zheng-Wei Lee

2017-10-01

Full Text Available Slow and continuous release of H2S by GYY4137 has previously been demonstrated to kill cancer cells by increasing glycolysis and impairing anion exchanger and sodium/proton exchanger activity. This action is specific for cancer cells. The resulting lactate overproduction and defective pH homeostasis bring about intracellular acidification-induced cancer cell death. The present study investigated the potency of H2S released by GYY4137 against invasive and radio- as well as chemo-resistant cancers, known to be glycolytically active. We characterized and utilized cancer cell line pairs of various organ origins, based on their aggressive behaviors, and assessed their response to GYY4137. We compared glycolytic activity, via lactate production, and intracellular pH of each cancer cell line pair after exposure to H2S. Invasive and therapy resistant cancers, collectively termed aggressive cancers, are receptive to H2S-mediated cytotoxicity, albeit at a higher concentration of GYY4137 donor. While lactate production was enhanced, intracellular pH of aggressive cancers was only modestly decreased. Inherently, the magnitude of intracellular pH decrease is a key determinant for cancer cell sensitivity to H2S. We demonstrated the utility of coupling GYY4137 with either simvastatin, known to inhibit monocarboxylate transporter 4 (MCT4, or metformin, to further boost glycolysis, in bringing about cell death for aggressive cancers. Simvastatin inhibiting lactate extrusion thence contained excess lactate induced by GYY4137 within intracellular compartment. In contrast, the combined exposure to both GYY4137 and metformin overwhelms cancer cells with lactate over-production exceeding its expulsion rate. Together, GYY4137 and simvastatin or metformin synergize to induce intracellular hyper-acidification-mediated cancer cell death.

Dying to Be Noticed: Epigenetic Regulation of Immunogenic Cell Death for Cancer Immunotherapy

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Brianne Cruickshank

2018-04-01

Full Text Available Immunogenic cell death (ICD activates both innate and adaptive arms of the immune system during apoptotic cancer cell death. With respect to cancer immunotherapy, the process of ICD elicits enhanced adjuvanticity and antigenicity from dying cancer cells and consequently, promotes the development of clinically desired antitumor immunity. Cancer ICD requires the presentation of various “hallmarks” of immunomodulation, which include the cell-surface translocation of calreticulin, production of type I interferons, and release of high-mobility group box-1 and ATP, which through their compatible actions induce an immune response against cancer cells. Interestingly, recent reports investigating the use of epigenetic modifying drugs as anticancer therapeutics have identified several connections to ICD hallmarks. Epigenetic modifiers have a direct effect on cell viability and appear to fundamentally change the immunogenic properties of cancer cells, by actively subverting tumor microenvironment-associated immunoevasion and aiding in the development of an antitumor immune response. In this review, we critically discuss the current evidence that identifies direct links between epigenetic modifications and ICD hallmarks, and put forward an otherwise poorly understood role for epigenetic drugs as ICD inducers. We further discuss potential therapeutic innovations that aim to induce ICD during epigenetic drug therapy, generating highly efficacious cancer immunotherapies.

Cancer Cell Growth Inhibitory Effect of Bee Venom via Increase of Death Receptor 3 Expression and Inactivation of NF-kappa B in NSCLC Cells

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Kyung Eun Choi

2014-07-01

Full Text Available Our previous findings have demonstrated that bee venom (BV has anti-cancer activity in several cancer cells. However, the effects of BV on lung cancer cell growth have not been reported. Cell viability was determined with trypan blue uptake, soft agar formation as well as DAPI and TUNEL assay. Cell death related protein expression was determined with Western blotting. An EMSA was used for nuclear factor kappaB (NF-κB activity assay. BV (1–5 μg/mL inhibited growth of lung cancer cells by induction of apoptosis in a dose dependent manner in lung cancer cell lines A549 and NCI-H460. Consistent with apoptotic cell death, expression of DR3 and DR6 was significantly increased. However, deletion of DRs by small interfering RNA significantly reversed BV induced cell growth inhibitory effects. Expression of pro-apoptotic proteins (caspase-3 and Bax was concomitantly increased, but the NF-κB activity and expression of Bcl-2 were inhibited. A combination treatment of tumor necrosis factor (TNF-like weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, docetaxel and cisplatin, with BV synergistically inhibited both A549 and NCI-H460 lung cancer cell growth with further down regulation of NF-κB activity. These results show that BV induces apoptotic cell death in lung cancer cells through the enhancement of DR3 expression and inhibition of NF-κB pathway.

Chinese cultural dimensions of death, dying, and bereavement: focus group findings.

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Yick, Alice G; Gupta, Rashmi

2002-01-01

The purpose of this qualitative study is to describe Chinese immigrants and Chinese Americans' attitudes and practices about death, dying, and bereavement. To this end, three focus groups were conducted with social work graduate students, pastors and religious leaders, and service providers working in the Chinese American community in New York City. The United States is becoming increasingly multicultural, and Chinese Americans are the most rapidly growing Asian American group. Findings from this study revealed that many Chinese attitudes and practices about death and dying are rooted in Asian cultural values such as filial piety, centrality of the family, and emphasis of hierarchy. In addition, strains of Confucianism, Buddhism, Taoism, and local folklore are embedded in these death attitudes and practices. Based on themes extrapolated from the focus groups, recommendations are delineated for service providers in order to implement culturally-sensitive bereavement practices.

A unifying mechanism for cancer cell death through ion channel activation by HAMLET.

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Storm, Petter; Klausen, Thomas Kjaer; Trulsson, Maria; Ho C S, James; Dosnon, Marion; Westergren, Tomas; Chao, Yinxia; Rydström, Anna; Yang, Henry; Pedersen, Stine Falsig; Svanborg, Catharina

2013-01-01

Ion channels and ion fluxes control many aspects of tissue homeostasis. During oncogenic transformation, critical ion channel functions may be perturbed but conserved tumor specific ion fluxes remain to be defined. Here we used the tumoricidal protein-lipid complex HAMLET as a probe to identify ion fluxes involved in tumor cell death. We show that HAMLET activates a non-selective cation current, which reached a magnitude of 2.74±0.88 nA within 1.43±0.13 min from HAMLET application. Rapid ion fluxes were essential for HAMLET-induced carcinoma cell death as inhibitors (amiloride, BaCl2), preventing the changes in free cellular Na(+) and K(+) concentrations also prevented essential steps accompanying carcinoma cell death, including changes in morphology, uptake, global transcription, and MAP kinase activation. Through global transcriptional analysis and phosphorylation arrays, a strong ion flux dependent p38 MAPK response was detected and inhibition of p38 signaling delayed HAMLET-induced death. Healthy, differentiated cells were resistant to HAMLET challenge, which was accompanied by innate immunity rather than p38-activation. The results suggest, for the first time, a unifying mechanism for the initiation of HAMLET's broad and rapid lethal effect on tumor cells. These findings are particularly significant in view of HAMLET's documented therapeutic efficacy in human studies and animal models. The results also suggest that HAMLET offers a two-tiered therapeutic approach, killing cancer cells while stimulating an innate immune response in surrounding healthy tissues.

Triptolide induces lysosomal-mediated programmed cell death in MCF-7 breast cancer cells

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Owa C

2013-09-01

Full Text Available Chie Owa, Michael E Messina Jr, Reginald HalabyDepartment of Biology, Montclair State University, Montclair, NJ, USABackground: Breast cancer is a major cause of death; in fact, it is the most common type, in order of the number of global deaths, of cancer in women worldwide. This research seeks to investigate how triptolide, an extract from the Chinese herb Tripterygium wilfordii Hook F, induces apoptosis in MCF-7 human breast cancer cells. Accumulating evidence suggests a role for lysosomal proteases in the activation of apoptosis. However, there is also some controversy regarding the direct participation of lysosomal proteases in activation of key apoptosis-related caspases and release of mitochondrial cytochrome c. In the present study, we demonstrate that triptolide induces an atypical, lysosomal-mediated apoptotic cell death in MCF-7 cells because they lack caspase-3.Methods: MCF-7 cell death was characterized via cellular morphology, chromatin condensation, 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide colorimetric cell growth inhibition assay and the expression levels of proapoptotic proteins. Acridine orange and LysoTracker® staining were performed to visualize lysosomes. Lysosomal enzymatic activity was monitored using an acid phosphatase assay and western blotting of cathepsin B protein levels in the cytosolic fraction, which showed increased enzymatic activity in drug-treated cells.Results: These experiments suggest that triptolide-treated MCF-7 cells undergo atypical apoptosis and that, during the early stages, lysosomal enzymes leak into the cytosol, indicating lysosomal membrane permeability.Conclusion: Our results suggest that further studies are warranted to investigate triptolide's potential as an anticancer therapeutic agent.Keywords: triptolide, MCF-7 breast cancer cells, apoptosis, lysosomes, lysosomal membrane permeabilization (LMP

[Causes of death among prostate cancer patients of different ages].

Science.gov (United States)

Dariy, E V

2016-02-01

To date, there is no unified approach to evaluating and treating patients with suspected prostate cancer taking into account their age and comorbidities. That was the rationale for conducting this study. To assess the clinical course of prostate cancer in men of all ages with comorbidities. The study included 408 patients aged 50 to 92 years (mean age 74.3 years) with histologically verified prostate cancer. 30 (7.4%) patients had stage T1 disease, 273 (66.9%) - T2, 91 (22.3%) - T3 and 14 (3.4%) - T4. The maximum follow-up was 22 years, the minimum one - 6 months (on average 15.4 years). During the follow-up 159 patients died (39%), 51 of them (32%) of prostate cancer, 108 (68%) - from other diseases. Among the latter the causes of death were cancer (20.4%), cardiovascular and bronchopulmonary diseases (79.6%). Cancer-specific survival rate was 41.4 +/-12,4%, the survival rate for other diseases 23.4 +/-10,6% (pcancer, especially of old age, including the option for active surveillance of patients with clinically insignificant prostate cancer.

The prevalence of deranged C-reactive protein and albumin in patients with incurable cancer approaching death.

Science.gov (United States)

Gray, Sarah; Axelsson, Bertil

2018-01-01

Amongst patients with incurable cancer approaching death, cachexia is common and associated with adverse outcomes. The term cachexia lacks a universally accepted definition and there is no consensus regarding which variables are to be measured. Furthermore, an elevated C-reactive protein is a common clinical challenge in this patient group. This study aims to add to the ongoing discussion regarding the definition of cancer cachexia and to study the role of C-reactive protein and s-albumin in this context. A 1-year cohort, consisting of 155 cancer patients enrolled in a specialized palliative home care team in the city of Östersund, Sweden, that were deceased during the year of 2015 was studied. Laboratory measures were studied within 0-30 and 31-60 days prior to death. C-reactive protein >10 mg/L and coinciding s-albumin death was noted. The prevalence of "laboratory cachexia" was 85% 0-30 days prior to death compared to 66% 31-60 days prior to death (pdeath, with a median of 47 days. The median values for C-reactive protein and s-albumin within 0-30 days prior to death were 84mg/L and 23g/L respectively. Could markedly deranged values of C-reactive protein and s-albumin, such as found in this study, signal a relatively short remaining survival time in patients with incurable cancer and no clinical signs of ongoing infection? The role of "laboratory cachexia" in this context as well as the cut off values for the laboratory measures included may be further discussed.

Antitumor effects of a sirtuin inhibitor, tenovin-6, against gastric cancer cells via death receptor 5 up-regulation.

Directory of Open Access Journals (Sweden)

Sachiko Hirai

Full Text Available Up-regulated sirtuin 1 (SIRT1, an NAD+-dependent class III histone deacetylase, deacetylates p53 and inhibits its transcriptional activity, leading to cell survival. SIRT1 overexpression has been reported to predict poor survival in some malignancies, including gastric cancer. However, the antitumor effect of SIRT1 inhibition remains elusive in gastric cancer. Here, we investigated the antitumor mechanisms of a sirtuin inhibitor, tenovin-6, in seven human gastric cancer cell lines (four cell lines with wild-type TP53, two with mutant-type TP53, and one with null TP53. Interestingly, tenovin-6 induced apoptosis in all cell lines, not only those with wild-type TP53, but also mutant-type and null versions, accompanied by up-regulation of death receptor 5 (DR5. In the KatoIII cell line (TP53-null, DR5 silencing markedly attenuated tenovin-6-induced apoptosis, suggesting that the pivotal mechanism behind its antitumor effects is based on activation of the death receptor signal pathway. Although endoplasmic reticulum stress caused by sirtuin inhibitors was reported to induce DR5 up-regulation in other cancer cell lines, we could not find marked activation of its related molecules, such as ATF6, PERK, and CHOP, in gastric cancer cells treated with tenovin-6. Tenovin-6 in combination with docetaxel or SN-38 exerted a slight to moderate synergistic cytotoxicity against gastric cancer cells. In conclusion, tenovin-6 has potent antitumor activity against human gastric cancer cells via DR5 up-regulation. Our results should be helpful for the future clinical development of sirtuin inhibitors.

Immediate in vivo target-specific cancer cell death after near infrared photoimmunotherapy

Directory of Open Access Journals (Sweden)

Mitsunaga Makoto

2012-08-01

Full Text Available Abstract Background Near infrared (NIR photoimmunotherapy (PIT is a new type of cancer treatment based on a monoclonal antibody (mAb-NIR phthalocyanine dye, (IR700 conjugate. In vitro cancer-specific cell death occurs during NIR light exposure in cells previously incubated with mAb-IR700 conjugates. However, documenting rapid cell death in vivo is more difficult. Methods A luciferase-transfected breast cancer cell (epidermal growth factor receptor+, MDA-MB-468luc cells was produced and used for both in vitro and in vivo experiments for monitoring the cell killing effect of PIT. After validation of cytotoxicity with NIR exposure up to 8 J/cm2in vitro, we employed an orthotopic breast cancer model of bilateral MDA-MB-468luc tumors in female athymic mice, which subsequently received a panitumumab-IR700 conjugate in vivo. One side was used as a control, while the other was treated with NIR light of dose ranging from 50 to 150 J/cm2. Bioluminescence imaging (BLI was performed before and after PIT. Results Dose-dependent cell killing and regrowth was successfully monitored by the BLI signal in vitro. Although tumor sizes were unchanged, BLI signals decreased by >95% immediately after PIT in vivo when light intensity was high (>100 J/cm2, however, in mice receiving lower intensity NIR (50 J/cm2, tumors recurred with gradually increasing BLI signal. Conclusion PIT induced massive cell death of targeted tumor cells immediately after exposure of NIR light that was demonstrated with BLI in vivo.

An audit of the toxicology findings in 555 medico-legal autopsies finds manner of death changed in 5 cases.

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Langlois, Neil E I; Gilbert, John D; Heath, Karen J; Winskog, Calle; Kostakis, Chris

2013-03-01

An audit of toxicological analysis in Coronial autopsies performed at Forensic Science South Australia was conducted on the cases of three pathologists. Toxicological analysis had been performed in 555 (68 %) from a total of 815 autopsies. It was found that the proffered manner of death was changed from the provisional report (provided immediately after the post-mortem examination) in five cases (just under 1 %) as a consequence of the toxicological findings. This is a limited study as it is retrospective, not all cases had toxicological analysis and the findings are constrained by the range of the substances that could be detected. Nonetheless, the audit supports the application of toxicological analysis in medico-legal death investigation and suggests that an inclusive policy should be adopted.

Rational Design of Regulators of Programmed Cell Death in Human Breast Cancer

National Research Council Canada - National Science Library

Cowburn, David

2000-01-01

The purpose of this research is to develop a better understanding of the intricate pathways of cell death and their contributions to breast cancers, with the goal of designing potential therapeutic...

Patterns in place of cancer death in the State of Qatar: a population-based study.

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Mohsen, Hassan; Haddad, Pascale; Allam, Ayman; Hassan, Azza

2014-01-01

International studies show that most people prefer to die at home; however, hospitals remain the most common place of death (PoD). This study aims to investigate the patterns in PoD and the associated factors, which are crucial for end-of-life cancer care enhancement. This retrospective, population-based study analyzed all registered cancer deaths in Qatar between January 1, 2006 and December 31, 2012 (n = 1,224). The main outcome measures were patient characteristics: age, gender, nationality, cancer diagnosis, year of death, and PoD. Time trends for age-standardized proportions of death in individual PoDs were evaluated using chi-square analysis. Odds ratio (OR) were determined for variables associated with the most preferred (acute palliative care unit [APCU] and hematology/oncology ward) versus least preferred (ICU and general medicine ward) PoDs in Qatar, stratified by nationality. The hematology/oncology ward was the most common PoD (32.4%; 95% CI 26.7-35.3%) followed by ICU (31.4%; 95% CI 28.7-34.3%), APCU (26.9%; 95% CI 24.3-29.6%), and general medicine ward (9.2%; 95% CI 7.6-11.1%). APCU trended upward (+0.057/year; pQatar occur in hospital. As home was the preferred PoD for most people, effective home care and hospice programs are needed to improve end-of-life cancer care.

Senescent cells re-engineered to express soluble programmed death receptor-1 for inhibiting programmed death receptor-1/programmed death ligand-1 as a vaccination approach against breast cancer.

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Chen, Zehong; Hu, Kang; Feng, Lieting; Su, Ruxiong; Lai, Nan; Yang, Zike; Kang, Shijun

2018-06-01

Various types of vaccines have been proposed as approaches for prevention or delay of the onset of cancer by boosting the endogenous immune system. We previously developed a senescent-cell-based vaccine, induced by radiation and veliparib, as a preventive and therapeutic tool against triple-negative breast cancer. However, the programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) pathway was found to play an important role in vaccine failure. Hence, we further developed soluble programmed death receptor-1 (sPD1)-expressing senescent cells to overcome PD-L1/PD-1-mediated immune suppression while vaccinating to promote dendritic cell (DC) maturity, thereby amplifying T-cell activation. In the present study, sPD1-expressing senescent cells showed a particularly active status characterized by growth arrest and modified immunostimulatory cytokine secretion in vitro. As expected, sPD1-expressing senescent tumor cell vaccine (STCV/sPD-1) treatment attracted more mature DC and fewer exhausted-PD1 + T cells in vivo. During the course of the vaccine studies, we observed greater safety and efficacy for STCV/sPD-1 than for control treatments. STCV/sPD-1 pre-injections provided complete protection from 4T1 tumor challenge in mice. Additionally, the in vivo therapeutic study of mice with s.c. 4T1 tumor showed that STCV/sPD-1 vaccination delayed tumorigenesis and suppressed tumor progression at early stages. These results showed that STCV/sPD-1 effectively induced a strong antitumor immune response against cancer and suggested that it might be a potential strategy for TNBC prevention. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Changes in Siblings Over Time After the Death of a Brother or Sister From Cancer.

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Akard, Terrah Foster; Skeens, Micah A; Fortney, Christine A; Dietrich, Mary S; Gilmer, Mary Jo; Vannatta, Kathryn; Barrera, Maru; Davies, Betty; Wray, Sarah; Gerhardt, Cynthia A

2018-02-27

Limited research has examined the impact of a child's death from cancer on siblings. Even less is known about how these siblings change over time. This study compared changes in siblings 1 (T1) and 2 (T2) years after the death of a brother or sister from cancer based on bereaved parent and sibling interviews. Participants across 3 institutions represented 27 families and included bereaved mothers (n = 21), fathers (n = 15), and siblings (n = 26) ranging from 8 to 17 years old. Participants completed semistructured interviews. Content analysis identified emerging themes and included frequency counts of participant responses. McNemar tests examined differences in the frequency of responses between T1 and T2 data. Participants reported similar types of changes in bereaved siblings at both time points, including changes in sibling relationships, life perspectives, their personal lives, and school performance. A new theme of "openness" emerged at T2. Frequencies of responses differed according to mother, father, or sibling informant. Overall, participants less frequently reported changes at T2 versus T1. Compared with findings in the first year, participants reported greater sibling maturity at follow-up. Overall changes in bereaved siblings continued over 2 years with less frequency over time, with the exception of increases in maturity and openness. Providers can educate parents regarding the impact of death of a brother or sister over time. Nurses can foster open communication in surviving grieving siblings and parents as potential protective factors in families going through their grief.

Care managers' views on death and caring for older cancer patients in Japan.

Science.gov (United States)

Matsui, Miho; Kanai, Emi; Kitagawa, Akiko; Hattori, Keiko

2013-12-01

Care managers (CMs) have an important role in coordinating care for cancer patients who are in the end-of-life stage; however, little is known about their views of death and their experiences while caring for older cancer patients. This study was conducted to examine CMs' views of death and caring for older cancer patients in a home care setting in Japan. Convenience sampling was undertaken, and 35 offices from 43 approached services agreed to participate. The final valid sample included responses from 136 CMs (90.7%). Most CMs, including nurses, care workers, home helpers, and social workers in home care settings, experienced difficulty in managing the care of cancer patients in the end-of-life stage. Respondents reported a wide array of experiences with end-of-life care, care management, and seminar attendance, and their ages and Frommelt Attitude Toward Care of the Dying (FATCOD) scores were associated factors. Moreover, multiple regression analysis indicated that better attitudes toward caring for the dying were positively associated with seminar attendance. These results suggest that CMs need education about palliative and end-of-life care in order to promote good home care for cancer patients.

The prevalence of deranged C-reactive protein and albumin in patients with incurable cancer approaching death.

Directory of Open Access Journals (Sweden)

Sarah Gray

Full Text Available Amongst patients with incurable cancer approaching death, cachexia is common and associated with adverse outcomes. The term cachexia lacks a universally accepted definition and there is no consensus regarding which variables are to be measured. Furthermore, an elevated C-reactive protein is a common clinical challenge in this patient group. This study aims to add to the ongoing discussion regarding the definition of cancer cachexia and to study the role of C-reactive protein and s-albumin in this context.A 1-year cohort, consisting of 155 cancer patients enrolled in a specialized palliative home care team in the city of Östersund, Sweden, that were deceased during the year of 2015 was studied. Laboratory measures were studied within 0-30 and 31-60 days prior to death. C-reactive protein >10 mg/L and coinciding s-albumin <30 g/L was referred to as "laboratory cachexia". Also, the number of days from the first found "laboratory cachexia" until death was noted.The prevalence of "laboratory cachexia" was 85% 0-30 days prior to death compared to 66% 31-60 days prior to death (p<0.01. The majority of patients (75% had an onset of "laboratory cachexia" within 0-120 days prior to death, with a median of 47 days. The median values for C-reactive protein and s-albumin within 0-30 days prior to death were 84mg/L and 23g/L respectively.Could markedly deranged values of C-reactive protein and s-albumin, such as found in this study, signal a relatively short remaining survival time in patients with incurable cancer and no clinical signs of ongoing infection? The role of "laboratory cachexia" in this context as well as the cut off values for the laboratory measures included may be further discussed.

Game theory in the death galaxy: interaction of cancer and stromal cells in tumour microenvironment.

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Wu, Amy; Liao, David; Tlsty, Thea D; Sturm, James C; Austin, Robert H

2014-08-06

Preventing relapse is the major challenge to effective therapy in cancer. Within the tumour, stromal (ST) cells play an important role in cancer progression and the emergence of drug resistance. During cancer treatment, the fitness of cancer cells can be enhanced by ST cells because their molecular signalling interaction delays the drug-induced apoptosis of cancer cells. On the other hand, competition among cancer and ST cells for space or resources should not be ignored. We explore the population dynamics of multiple myeloma (MM) versus bone marrow ST cells by using an experimental microecology that we call the death galaxy, with a stable drug gradient and connected microhabitats. Evolutionary game theory is a quantitative way to capture the frequency-dependent nature of interactive populations. Therefore, we use evolutionary game theory to model the populations in the death galaxy with the gradients of pay-offs and successfully predict the future densities of MM and ST cells. We discuss the possible clinical use of such analysis for predicting cancer progression.

Heat-modified citrus pectin induces apoptosis-like cell death and autophagy in HepG2 and A549 cancer cells.

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Leclere, Lionel; Fransolet, Maude; Cote, Francois; Cambier, Pierre; Arnould, Thierry; Van Cutsem, Pierre; Michiels, Carine

2015-01-01

Cancer is still one of the leading causes of death worldwide, and finding new treatments remains a major challenge. Previous studies showed that modified forms of pectin, a complex polysaccharide present in the primary plant cell wall, possess anticancer properties. Nevertheless, the mechanism of action of modified pectin and the pathways involved are unclear. Here, we show that citrus pectin modified by heat treatment induced cell death in HepG2 and A549 cells. The induced cell death differs from classical apoptosis because no DNA cleavage was observed. In addition, Z-VAD-fmk, a pan-caspase inhibitor, did not influence the observed cell death in HepG2 cells but appeared to be partly protective in A549 cells, indicating that heat-modified citrus pectin might induce caspase-independent cell death. An increase in the abundance of the phosphatidylethanolamine-conjugated Light Chain 3 (LC3) protein and a decrease in p62 protein abundance were observed in both cell types when incubated in the presence of heat-modified citrus pectin. These results indicate the activation of autophagy. To our knowledge, this is the first time that autophagy has been revealed in cells incubated in the presence of a modified form of pectin. This autophagy activation appears to be protective, at least for A549 cells, because its inhibition with 3-methyladenine increased the observed modified pectin-induced cytotoxicity. This study confirms the potential of modified pectin to improve chemotherapeutic cancer treatments.

Heat-modified citrus pectin induces apoptosis-like cell death and autophagy in HepG2 and A549 cancer cells.

Directory of Open Access Journals (Sweden)

Lionel Leclere

Full Text Available Cancer is still one of the leading causes of death worldwide, and finding new treatments remains a major challenge. Previous studies showed that modified forms of pectin, a complex polysaccharide present in the primary plant cell wall, possess anticancer properties. Nevertheless, the mechanism of action of modified pectin and the pathways involved are unclear. Here, we show that citrus pectin modified by heat treatment induced cell death in HepG2 and A549 cells. The induced cell death differs from classical apoptosis because no DNA cleavage was observed. In addition, Z-VAD-fmk, a pan-caspase inhibitor, did not influence the observed cell death in HepG2 cells but appeared to be partly protective in A549 cells, indicating that heat-modified citrus pectin might induce caspase-independent cell death. An increase in the abundance of the phosphatidylethanolamine-conjugated Light Chain 3 (LC3 protein and a decrease in p62 protein abundance were observed in both cell types when incubated in the presence of heat-modified citrus pectin. These results indicate the activation of autophagy. To our knowledge, this is the first time that autophagy has been revealed in cells incubated in the presence of a modified form of pectin. This autophagy activation appears to be protective, at least for A549 cells, because its inhibition with 3-methyladenine increased the observed modified pectin-induced cytotoxicity. This study confirms the potential of modified pectin to improve chemotherapeutic cancer treatments.

Deaths from nasopharyngeal cancer among waiters and waitresses in Chinese restaurants.

Science.gov (United States)

Yu, Ignatius T S; Chiu, Yuk-lan; Wong, Tze-wai; Tang, Jin-ling

2004-10-01

Previous studies have shown that waiters have a high risk of developing cancers of the buccal cavity and pharynx, but nasopharyngeal cancer (NPC) has not been specifically studied. This study was carried out to investigate whether waiters/waitresses in Chinese restaurants have an increased risk of dying from NPC. A mortality odds ratio study was used to estimate the relative risk of dying from NPC for waiters/waitresses working in Chinese restaurants in Hong Kong during the period 1986-1995, using the general population as the external comparison group and deceased kitchen workers as an internal comparison group. Cases were deaths from NPC and the controls were deaths from the selected sets of reference causes. Seventeen deaths from NPC were identified among 415 deceased waiters and four NPC deaths occurred among 140 deceased waitresses. The adjusted mortality odds ratio (aMOR) for NPC was increased among waiters, being 3.02 (95% CI 1.82-5.00) and 2.61 (95% CI 1.02-6.69) in the external and internal comparisons, respectively. For waitresses, the aMOR was 4.58 (95% CI 1.63-12.86) in the external comparison. Analysis by duration of union membership suggested a dose-response relationship. An increased risk of dying from NPC was observed among waiters/waitresses and could not be fully explained by bias or confounding factors. Possible risk factors related to poor indoor air quality in the service areas of Chinese restaurants in Hong Kong should be further investigated.

Providing clinicians and patients with actual prognosis: cancer in the context of competing causes of death.

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Howlader, Nadia; Mariotto, Angela B; Woloshin, Steven; Schwartz, Lisa M

2014-11-01

To isolate progress against cancer from changes in competing causes of death, population cancer registries have traditionally reported cancer prognosis (net measures). But clinicians and cancer patients generally want to understand actual prognosis (crude measures): the chance of surviving, dying from the specific cancer and from competing causes of death in a given time period. To compare cancer and actual prognosis in the United States for four leading cancers-lung, breast, prostate, and colon-by age, comorbidity, and cancer stage and to provide templates to help patients, clinicians, and researchers understand actual prognosis. Using population-based registry data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated cancer prognosis (relative survival) and actual prognosis (five-year overall survival and the "crude" probability of dying from cancer and competing causes) for three important prognostic determinants (age, comorbidity [Charlson-score from 2012 SEER-Medicare linkage dataset] and cancer stage at diagnosis). For younger, healthier, and earlier stage cancer patients, cancer and actual prognosis estimates were quite similar. For older and sicker patients, these prognosis estimates differed substantially. For example, the five-year overall survival for an 85-year-old patient with colorectal cancer is 54% (cancer prognosis) versus 22% (actual prognosis)-the difference reflecting the patient's substantial chance of dying from competing causes. The corresponding five-year chances of dying from the patient's cancer are 46% versus 37%. Although age and comorbidity lowered actual prognosis, stage at diagnosis was the most powerful factor: The five-year chance of colon cancer death was 10% for localized stage and 83% for distant stage. Both cancer and actual prognosis measures are important. Cancer registries should routinely report both cancer and actual prognosis to help clinicians and researchers understand the difference between

Curcumin induces apoptosis-independent death in oesophageal cancer cells.

LENUS (Irish Health Repository)

O'Sullivan-Coyne, G

2009-10-06

Background:Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines.Methods:MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting.Results:Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2\\/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug.Conclusion:Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.British Journal of Cancer advance online publication, 6 October 2009; doi:10.1038\\/sj.bjc.6605308 www.bjcancer.com.

Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism

International Nuclear Information System (INIS)

Baba, Miyako; Inoue, Masahiro; Itoh, Kazuyuki; Nishizawa, Yasuko

2008-01-01

CD147 is a multifunctional transmembrane protein and promotes cancer progression. We found that the anti-human CD147 mouse monoclonal antibody MEM-M6/1 strongly induces necrosis-like cell death in LoVo, HT-29, WiDr, and SW620 colon cancer cells and A2058 melanoma cells, but not in WI-38 and TIG-113 normal fibroblasts. Silencing or overexpression of CD147 in LoVo cells enhanced or decreased the MEM-M6/1 induced cell death, respectively. CD147 is known to form complex with proton-linked monocarboxylate transporters (MCTs), which is critical for lactate transport and intracellular pH (pHi) homeostasis. In LoVo cells, CD147 and MCT-1 co-localized on the cell surface, and MEM-M6/1 inhibited the association of these molecules. MEM-M6/1 inhibited lactate uptake, lactate release, and reduced pHi. Further, the induction of acidification was parallel to the decrease of the glycolytic flux and intracellular ATP levels. These effects were not found in the normal fibroblasts. As cancer cells depend on glycolysis for their energy production, CD147 inhibition might induce cell death specific to cancer cells

Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney disease and end-stage renal disease.

Science.gov (United States)

Orskov, Bjarne; Sørensen, Vibeke Rømming; Feldt-Rasmussen, Bo; Strandgaard, Svend

2012-04-01

With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31 December 2008. Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular, cerebrovascular, infection, other and unknown. Cardiovascular disease was the major cause of death. A multivariate competing risk model comparing the two 8-year periods, adjusted for age at ESRD, gender and treatment modality, showed that deaths from cardiovascular disease decreased by 35% [hazard ratios (HR) 0.65, P=0.008] and deaths from cerebrovascular disease decreased by 69% (HR 0.31, P=0.0003) from the first to the second time period. There were no significant changes between the time periods in death from cancer, infection, other or unknown. From the first to the second 8-year interval, the prevalence of cancer increased by 35% (P=0.0002) while the cancer incidence was stable. In Danish patients with ADPKD and ESRD, there was a significant reduction in cardiovascular and cerebrovascular deaths from 1993 to 2008. The prevalence of cancer increased without significant change in cancer incidence or deaths from cancer.

Apoptotic induction of skin cancer cell death by plant extracts.

Science.gov (United States)

Thuncharoen, Walairat; Chulasiri, Malin; Nilwarangkoon, Sirinun; Nakamura, Yukio; Watanapokasin, Ramida

2013-01-01

The aim of the present study was to investigate the effects of plant extracts on cancer apoptotic induction. Human epidermoid carcinoma A431 cell line, obtained from the American Type Culture Collection (ATCC, Manassas, VA), was maintained in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) at 37 degrees C, 5% carbon dioxide (CO2). Plant extract solutions were obtained from S & J international enterprises public company limited. These plant extracts include 50% hydroglycol extracts from Etlingera elatior (Jack) R.M.Smith (torch ginger; EE), Rosa damascene (damask rose; DR) and Rafflesia kerrii Meijer (bua phut; RM). The cell viability, time and dose dependency were determined by MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assay. A431 cells were treated with the plant extracts and stained with Hoechst 33342 fluorescent staining dye. Cell viability was demonstrated by the inhibitory concentration 50% (IC50). The anti-proliferative effects were shown to be dependent on time and dose. Typical characteristics of apoptosis which are cell morphological changes and chromatin condensation were clearly observed. The plant extracts was shown to be effective for anti-proliferation and induction of apoptosis cell death in skin cancer cells. Therefore, mechanisms underlying the cell death and its potential use for treatment of skin cancer will be further studied.

Leading Causes of Death among Asian American Subgroups (2003-2011.

Directory of Open Access Journals (Sweden)

Katherine G Hastings

Full Text Available Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups.We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese and non-Hispanic Whites (NHWs from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%. Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs.Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.

Leading Causes of Death among Asian American Subgroups (2003-2011).

Science.gov (United States)

Hastings, Katherine G; Jose, Powell O; Kapphahn, Kristopher I; Frank, Ariel T H; Goldstein, Benjamin A; Thompson, Caroline A; Eggleston, Karen; Cullen, Mark R; Palaniappan, Latha P

2015-01-01

Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups. We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs. Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.

Patterns in Place of Cancer Death in the State of Qatar: A Population-Based Study

Science.gov (United States)

Mohsen, Hassan; Haddad, Pascale; Allam, Ayman; Hassan, Azza

2014-01-01

Background International studies show that most people prefer to die at home; however, hospitals remain the most common place of death (PoD). This study aims to investigate the patterns in PoD and the associated factors, which are crucial for end-of-life cancer care enhancement. Method This retrospective, population-based study analyzed all registered cancer deaths in Qatar between January 1, 2006 and December 31, 2012 (n = 1,224). The main outcome measures were patient characteristics: age, gender, nationality, cancer diagnosis, year of death, and PoD. Time trends for age-standardized proportions of death in individual PoDs were evaluated using chi-square analysis. Odds ratio (OR) were determined for variables associated with the most preferred (acute palliative care unit [APCU] and hematology/oncology ward) versus least preferred (ICU and general medicine ward) PoDs in Qatar, stratified by nationality. Results The hematology/oncology ward was the most common PoD (32.4%; 95% CI 26.7–35.3%) followed by ICU (31.4%; 95% CI 28.7–34.3%), APCU (26.9%; 95% CI 24.3–29.6%), and general medicine ward (9.2%; 95% CI 7.6–11.1%). APCU trended upward (+0.057/year; pQatar occur in hospital. As home was the preferred PoD for most people, effective home care and hospice programs are needed to improve end-of-life cancer care. PMID:25536076

Epidemiologic study of uterine cancer, Hiroshima

Energy Technology Data Exchange (ETDEWEB)

Ishimaru, Toranosuke

1965-12-10

As a cause of death in females, cancer of the uterus is one of the important cancers in Japan. In 1962 it was responsible for 15.5% of all the deaths due to cancer in women and ranked next to the proportion attributed to cancer of the stomach. The JNIH-ABCC Life Span Study of A-bomb survivors also shows that cancer of the stomach and uterus were the major causes of cancer deaths in the female population. The present study, which was carried out in 1963, was begun in the hope of elucidating some of the relationships of the factors other than radiation possibly associated with the incidence of cancer of the uterus in the Life Span Study (ST 100) sample in Horoshima. Environmental factors considered to play a role in the development of uterine cancer were studied by interview with a close relative of the subject. The data did not clearly support the findings reported elsewhere that residential history, occupational history, history of marital status, smoking and alcohol drinking habits, and socioeconomic factors were associated with the incidence of cancer of the uterus. A brief analysis was also conducted for the accuracy of death certificates. The results suggest that an epidemiologic study should be conducted on morbidity data derived from pathologic findings and a revised plan is desirable to elucidate the factors associated with the incidence of cancer of the uterus using the various recent experimental findings as references. 124 references, 15 tables.

Years of Life and Productivity Loss from Potentially Avoidable Colorectal Cancer Deaths in U.S. Counties with Lower Educational Attainment (2008–2012)

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Weir, Hannah K.; Li, Chunyu; Henley, S. Jane; Joseph, Djenaba

2018-01-01

Background Educational attainment (EA) is inversely associated with colorectal cancer risk. Colorectal cancer screening can save lives if precancerous polyps or early cancers are found and successfully treated. This study aims to estimate the potential productivity loss (PPL) and associated avoidable colorectal cancer–related deaths among screen-eligible adults residing in lower EA counties in the United States. Methods Mortality and population data were used to examine colorectal cancer deaths (2008–2012) among adults aged 50 to 74 years in lower EA counties, and to estimate the expected number of deaths using the mortality experience from high EA counties. Excess deaths (observed–expected) were used to estimate potential years life lost, and the human capital method was used to estimate PPL in 2012 U.S. dollars. Results County-level colorectal cancer death rates were inversely associated with county-level EA. Of the 100,857 colorectal cancer deaths in lower EA counties, we estimated that more than 21,000 (1 in 5) was potentially avoidable and resulted in nearly $2 billion annual productivity loss. Conclusions County-level EA disparities contribute to a large number of potentially avoidable colorectal cancer–related deaths. Increased prevention and improved screening potentially could decrease deaths and help reduce the associated economic burden in lower EA communities. Increased screening could further reduce deaths in all EA groups. Impact These results estimate the large economic impact of potentially avoidable colorectal cancer–related deaths in economically disadvantaged communities, as measured by lower EA. PMID:28003180

Radiologic findings of male breast cancer: two cases report

Energy Technology Data Exchange (ETDEWEB)

Chung, Soo Young; Kim, Sook Hyun; Bae, Sang Hoon; Ahn, Hye Kyung [Hallym University College of Medicine, Seoul (Korea, Republic of)

1993-09-15

Male breast cancer is very rare, with the incidence of 0.15-1% of all breast cancers and less than 1% of all cancers in men. The prognosis of male breast cancer is poorer than that of female because the median age of detection of the disease is in more late stage. It usually involves higher axillary lymph nodes. We report two case of male breast cancer to describe characteristic mammographic and ultrasonographic findings and to compare with the findings of gynaecomastia.

Life and death.

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Lloyd, J W

1983-03-01

In contrast with the other lectures given in the course on humanics and bioethics at the UOEH, which address the questions of life and death from the standpoint of the physician or the philosopher, this lecture considers these issues as seen by the cancer patient who has had a close encounter with death. The attitudes of Americans concerning abortion, the use of life-support systems, "mercy killings", suicide and the use of cancer chemotherapy are discussed with particular emphasis on restraints imposed by the courts, the churches and the family systems. An attempt is made to contrast the American and Japanese attitudes on these questions but this is difficult because of different cultural and religious backgrounds. The author describes his own experiences as a cancer patient who has approached death very closely and the changes in his own attitude toward life which results from the encounter with death. He also talks about the joy of being alive and describes his own experience with receiving cancer chemotherapy, the resulting discomfort and inconveniences and his feelings about a "tolerable" existence. Finally, the author considers the question of the "quality of life" for the cancer patient who has a violent reaction to certain forms of chemotherapy. This is a dilemma for the patient and the doctor who must consider the choice between death and a miserable existence.

Corn silk maysin induces apoptotic cell death in PC-3 prostate cancer cells via mitochondria-dependent pathway.

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Lee, Jisun; Lee, Seul; Kim, Sun-Lim; Choi, Ji Won; Seo, Jeong Yeon; Choi, Doo Jin; Park, Yong Il

2014-12-05

Despite recent advances in prostate cancer diagnostics and therapeutics, the overall survival rate still remains low. This study was aimed to assess potential anti-cancer activity of maysin, a major flavonoid of corn silk (CS, Zea mays L.), in androgen-independent human prostate cancer cells (PC-3). Maysin was isolated from CS of Kwangpyeongok, a Korean hybrid corn, via methanol extraction and preparative C18 reverse phase column chromatography. Maysin cytotoxicity was determined by either monitoring cell viability in various cancer cell lines by MTT assay or morphological changes. Apoptotic cell death was assessed by annexin V-FITC/PI double staining, depolarization of mitochondrial membrane potential (MMP), expression levels of Bcl-2 and pro-caspase-3 and by terminal transferase mediated dUTP-fluorescein nick end labeling (TUNEL) staining. Underlying mechanism in maysin-induced apoptosis of PC-3 cells was explored by evaluating its effects on Akt and ERK pathway. Maysin dose-dependently reduced the PC-3 cell viability, with an 87% reduction at 200 μg/ml. Maysin treatment significantly induced apoptotic cell death, DNA fragmentation, depolarization of MMP, and reduction in Bcl-2 and pro-caspase-3 expression levels. Maysin also significantly attenuated phosphorylation of Akt and ERK. A combined treatment with maysin and other known anti-cancer agents, including 5-FU, etoposide, cisplatin, or camptothecin, synergistically enhanced PC-3 cell death. These results suggested for the first time that maysin inhibits the PC-3 cancer cell growth via stimulation of mitochondria-dependent apoptotic cell death and may have a strong therapeutic potential for the treatment of either chemo-resistant or androgen-independent human prostate cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Pneumonitis and pneumonitis-related death in cancer patients treated with programmed cell death-1 inhibitors: a systematic review and meta-analysis

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Cui P

2017-09-01

Full Text Available Peng-Fei Cui,1–3,* Jun-Xun Ma,1,* Fei-Xue Wang,1,* Jing Zhang,1 Hai-Tao Tao,1 Yi Hu1 1First Department of Medical Oncology, 2Department of Graduate Administration, Chinese PLA General Hospital, Beijing, 3Health Bureau of the 75709 Army, Central Theater of the Chinese PLA, Wuhan, China *These authors contributed equally to this work Purpose: We conducted a meta-analysis of published clinical trials to determine the relationship between the risks of pneumonitis and pneumonitis-related death and programmed cell death-1 (PD-1 inhibitor treatment in patients with cancer.Materials and methods: We examined clinical trials from the Medline and Google Scholar databases. Data from original studies and review articles were also cross-referenced and evaluated. Randomized Phase II and Phase III trials of pembrolizumab and nivolumab treatment in patients with cancer were eligible for the analysis. Information about the participants, all-grade and high-grade pneumonitis, and pneumonitis-related death was extracted from each study and analyzed.Results: After the exclusion of ineligible studies, 12 clinical trials were included in the analysis. The odds ratio (OR for all-grade pneumonitis after PD-1 inhibitor treatment was 4.59 (95% confidence interval [CI]: 2.51–8.37; P<0.00001, and the OR for high-grade pneumonitis after PD-1 inhibitor treatment was 3.83 (95% CI: 1.54–9.48; P=0.004. The OR for pneumonitis-related death after PD-1 inhibitor treatment was 2.47 (95% CI: 0.41–14.81; P=0.32. Moreover, the OR for all-grade pneumonitis after nivolumab/ipilimumab combination therapy versus nivolumab monotherapy was 3.54 (95% CI: 1.52–8.23; P=0.003, and that for high-grade pneumonitis after nivolumab/ipilimumab combination therapy versus nivolumab monotherapy was 2.35 (95% CI: 0.45–12.13; P=0.31. Treated cancer appeared to have no effect on the risk of pneumonitis.Conclusion: Our data showed that PD-1 inhibitors were associated with increased risks of all

Dehydroabietic Acid Derivative QC4 Induces Gastric Cancer Cell Death via Oncosis and Apoptosis

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Dongjun Luo

2016-01-01

Full Text Available Aim. QC4 is the derivative of rosin’s main components dehydroabietic acid (DHA. We investigated the cytotoxic effect of QC4 on gastric cancer cells and revealed the mechanisms beneath the induction of cell death. Methods. The cytotoxic effect of QC4 on gastric cancer cells was evaluated by CCK-8 assay and flow cytometry. The underlying mechanisms were tested by administration of cell death related inhibitors and detection of apoptotic and oncosis related proteins. Cytomembrane integrity and organelles damage were confirmed by lactate dehydrogenase (LDH leakage assay, mitochondrial function test, and cytosolic free Ca2+ concentration detection. Results. QC4 inhibited cell proliferation dose- and time-dependently and destroyed cell membrane integrity, activated calpain-1 autolysis, and induced apoptotic protein cleavage in gastric cancer cells. The detection of decreased ATP and mitochondrial membrane potential, ROS accumulation, and cytosolic free Ca2+ elevation confirmed organelles damage in QC4-treated gastric cancer cells. Conclusions. DHA derivative QC4 induced the damage of cytomembrane and organelles which finally lead to oncosis and apoptosis in gastric cancer cells. Therefore, as a derivative of plant derived small molecule DHA, QC4 might become a promising agent in gastric cancer therapy.

Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway

International Nuclear Information System (INIS)

Jo, Miran; Park, Mi Hee; Kollipara, Pushpa Saranya; An, Byeong Jun; Song, Ho Sueb; Han, Sang Bae; Kim, Jang Heub; Song, Min Jong; Hong, Jin Tae

2012-01-01

We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1–5 μg/ml) and melittin (0.5–2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, 8, and Bax was concomitantly increased, but the phosphorylation of JAK2 and STAT3 and the expression of Bcl-2 were inhibited by treatment with bee venom and melittin in SKOV3 and PA-1 cells. Expression of cleaved caspase-3 was increased in SKOV3, but cleaved caspase-8 was increased in PA-1 cells. Moreover, deletion of DR3, DR4, and DR6 by small interfering RNA significantly reversed bee venom and melittin-induced cell growth inhibitory effect as well as down regulation of STAT3 by bee venom and melittin in SKOV3 and PA-1 ovarian cancer cell. These results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway. -- Highlights: ► Some studies have showed that bee venom and/or melittin have anti-cancer effects. ► We found that bee venom and melittin inhibited cell growth in ovarian cancer cells. ► Bee venom and melittin induce apoptosis in SKOV3 and PA-1.

Murraya koenigii leaf extract inhibits proteasome activity and induces cell death in breast cancer cells.

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Noolu, Bindu; Ajumeera, Rajanna; Chauhan, Anitha; Nagalla, Balakrishna; Manchala, Raghunath; Ismail, Ayesha

2013-01-09

Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, polyphenols/flavonoids have been reported to inhibit proteasome activity. Murraya koenigii Spreng, a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine. Here we show that Murraya koenigii leaves (curry leaves), a rich source of polyphenols, inhibit the proteolytic activity of the cancer cell proteasome, and cause cell death. Hydro-methanolic extract of curry leaves (CLE) was prepared and its total phenolic content [TPC] determined by, the Folin-Ciocalteau's method. Two human breast carcinoma cell lines: MCF-7 and MDA-MB-231 and a normal human lung fibroblast cell line, WI-38 were used for the studies. Cytotoxicity of the CLE was assessed by the MTT assay. We studied the effect of CLE on growth kinetics using colony formation assay. Growth arrest was assessed by cell cycle analysis and apoptosis by Annexin-V binding using flow cytometry. Inhibition of the endogenous 26S proteasome was studied in intact cells and cell extracts using substrates specific to 20S proteasomal enzymes. CLE decreased cell viability and altered the growth kinetics in both the breast cancer cell lines in a dose-dependent manner. It showed a significant arrest of cells in the S phase albeit in cancer cells only. Annexin V binding data suggests that cell death was via the apoptotic pathway in both the cancer cell lines. CLE treatment significantly decreased the activity of the 26S proteasome in the cancer but not normal cells. Our study suggests M. koenigii leaves to be a potent source of proteasome inhibitors that lead to cancer cell death. Therefore, identification of active component(s) from the leaf

US findings of bilateral primary breast cancer: Retrospective study

International Nuclear Information System (INIS)

Lou Li; Cong Xinli; Yu Guofang; Li Jichang; Ma Yuxiang

2007-01-01

Background: For women with breast cancer, the contralateral breast is at high risk. The bilateral cancers may be synchronous or metachronous. If the bilateral breast cancers have similar ultrasonography (US) appearances, the US findings of the first breast cancer (index cancer) might lead to early detection of the contralateral cancer. The purpose of this study was to identify the US characteristics of bilateral breast cancer and to determine whether bilateral breast cancers have similar US appearances and whether the US findings for one breast cancer might be predictive of the contralateral breast cancer. Methods: We retrospectively reviewed the US manifestations of 58 patients with surgically proven bilateral primary breast cancer and compared the contralateral cancer with the index cancer by evaluation the margin, shape, inside echoes, posterior attenuation, calcification and color flow signals of 58 lesion pairs to investigate whether the bilateral breast cancers have similar US appearances. Results: Bilateral primary breast cancers were more located in upper outer quadrant, frequently spiculation, taller than wide shape, with irregular margin, heterogeneous internal echo and acoustic shadowing, containing microcalcification and abundant color flow signals. The most common US appearances were taller than wide shape (75.0%, 87/116), irregular margins (79.3%, 92/116) and heterogeneous internal echo (86.2%, 100/116). Of the total 58 lesion pairs, 18 (31.0%) pairs had similar US characteristics, whereas 40 (69.0%) pairs had different US characteristics. Conclusions: US signs of the index cancer do not indicate the most likely appearance of the second cancer in the contralateral breast. Evaluation of the contralateral cancer should be performed without regard for the US findings for the index cancer

Induction of cancer cell death by proton beam in tumor hypoxic region

International Nuclear Information System (INIS)

Hur, T. R.; Lee, Y. M.; Park, J. W.; Sohn, E. J.

2006-05-01

The physical properties of charged particles such as protons are uniquely suited to target the radiation dose precisely in the tumor. In proton therapy, the Bragg peak is spread out by modulating or degrading the energy of the particles to cover a well defined target volume at a given depth. Due to heterogeneity in the various tumors and end-points as well as in the physical properties of the beams considered, it is difficult to fit the various results into a clear general description of the biological effect of proton in tumor therapy. Tumor hypoxia is a main obstacle to radiotherapy, including gamma-ray. Survived tumor cells under hypoxic region are resistant to radiation and more aggressive to be metastasized. To investigate the dose of proton beam to induce cell death of various tumor cells and hypoxic tumor cells at the Bragg peak in vitro, we used 3 kinds of tumor cells, lung cancer, leukemia and hepatoma cells. Proton beam induces apoptosis in Lewis lung carcinoma cells dose dependently and, slightly in leukemia but not in hepatoma cells at all. Above 1000 gray of proton beam, 60% of cells died even the hypoxic cells in Lewis lung carcinoma cells. But the Molt-4 leukemia cells showed milder effect, 20% cell death by the above 1000 Gray of proton beam and typical resistant pattern (5-10%) of hypoxia in desferrioxamine treated cells. Hepatoma cells (HepG2) were not responsive to proton beam even in rather higher dose (4000G). However, by the gamma-irradiation, Molt-4 was more sensitive than hepatoma or lung cancer cells, but still showed hypoxic resistance. The cell death by proton beam in Lewis lung carcinoma cells was confirmed by PARP cleavage and may be mediated by increased p53. Pro-caspases were also activated and cleaved by the proton beam irradiations for lung cancer cell death. In conclusion, high dose of proton beam (above 1000 gray) may be a good therapeutic radiation even in hypoxic region at the Bragg peak, but further investigations about the

Curcumin induces apoptosis-independent death in oesophageal cancer cells.

LENUS (Irish Health Repository)

O'Sullivan-Coyne, G

2012-01-31

BACKGROUND: Oesophageal cancer incidence is increasing and survival rates remain extremely poor. Natural agents with potential for chemoprevention include the phytochemical curcumin (diferuloylmethane). We have examined the effects of curcumin on a panel of oesophageal cancer cell lines. METHODS: MTT (3-(4,5-dimethyldiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assays and propidium iodide staining were used to assess viability and DNA content, respectively. Mitotic catastrophe (MC), apoptosis and autophagy were defined by both morphological criteria and markers such as MPM-2, caspase 3 cleavage and monodansylcadaverine (MDC) staining. Cyclin B and poly-ubiquitinated proteins were assessed by western blotting. RESULTS: Curcumin treatment reduces viability of all cell lines within 24 h of treatment in a 5-50 muM range. Cytotoxicity is associated with accumulation in G2\\/M cell-cycle phases and distinct chromatin morphology, consistent with MC. Caspase-3 activation was detected in two out of four cell lines, but was a minor event. The addition of a caspase inhibitor zVAD had a marginal or no effect on cell viability, indicating predominance of a non-apoptotic form of cell death. In two cell lines, features of both MC and autophagy were apparent. Curcumin-responsive cells were found to accumulate poly-ubiquitinated proteins and cyclin B, consistent with a disturbance of the ubiquitin-proteasome system. This effect on a key cell-cycle checkpoint regulator may be responsible for the mitotic disturbances and consequent cytotoxicity of this drug. CONCLUSION: Curcumin can induce cell death by a mechanism that is not reliant on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of oesophageal cancer.

Contributions of Health and Demographic Status to Death Anxiety and Attitudes toward Voluntary Passive Euthanasia.

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Devins, Gerald M.

1980-01-01

Greater death acceptance and anxiety were observed among rural as compared to urban-dwelling participants. Responses by a life-threatened geriatric subsample revealed differences in death fears related to type of medical disorder. Previous findings of no difference in the death fears of heart and cancer patients were replicated. (Author)

The novel anthraquinone derivative IMP1338 induces death of human cancer cells by p53-independent S and G2/M cell cycle arrest.

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Choi, Hyun Kyung; Ryu, Hwani; Son, A-Rang; Seo, Bitna; Hwang, Sang-Gu; Song, Jie-Young; Ahn, Jiyeon

2016-04-01

To identify novel small molecules that induce selective cancer cell death, we screened a chemical library containing 1040 compounds in HT29 colon cancer and CCD18-Co normal colon cells, using a phenotypic cell-based viability assay system with the Cell Counting Kit-8 (CCK-8). We discovered a novel anthraquinone derivative, N-(4-[{(9,10-dioxo-9,10-dihydro-1-anthracenyl)sulfonyl}amino]phenyl)-N-methylacetamide (IMP1338), which was cytotoxic against the human colon cancer cells tested. The MTT cell viability assay showed that treatment with IMP1338 selectively inhibited HCT116, HCT116 p53(-/-), HT29, and A549 cancer cell proliferation compared to that of Beas2B normal epithelial cells. To elucidate the cellular mechanism underlying the cytotoxicity of IMP1338, we examined the effect of IMP1338 on the cell cycle distribution and death of cancer cells. IMP1338 treatment significantly arrested the cell cycle at S and G2/M phases by DNA damage and led to apoptotic cell death, which was determined using FACS analysis with Annexin V/PI double staining. Furthermore, IMP1338 increased caspase-3 cleavage in wild-type p53, p53 knockout HCT116, and HT29 cells as determined using immunoblotting. In addition, IMP1338 markedly induced the phosphorylation of histone H2AX and Chk1 in both cell lines while the combination of 5-fluorouracil (5-FU) and radiation inhibited the viability of HCT116, HCT116 p53(-/-), and HT29 cells compared to 5-FU or radiation alone. Our findings indicated that IMP1338 induced p53-independent cell death through S and G2/M phase arrest as well as DNA damage. These results provide a basis for future investigations assessing the promising anticancer properties of IMP1338. Copyright © 2016. Published by Elsevier Masson SAS.

Statistical Survey of Deaths from Non melanoma Skin Cancer in Japan during 54 Years

International Nuclear Information System (INIS)

Ohtsuka, H.

2011-01-01

The author analyzed the annual trends in the number of deaths from non melanoma skin cancer (NMSC) from 1955 to 2008 in Japan on the basis of the data from the Vital Statistics of Japan. The general trends in the number of deaths from NMSC were downward between 1979 to 1994, but upward after 1995. The general trends in age-standardized death rates were roughly downward, although the death rates plateaued after 1995. The recent annual increased ratio of deaths from NMSC was 3.8% (95% confidence interval: 2.7∼4.9%). The number and proportion of deaths from NMSC among the elderly were increasing in Japan. For females, more than 50% of the deaths occurred recently at or after 85 years of age, whereas, for males, this proportion was at or after 75 years of age, nearly reaching at or after 80 years of age.

Radiological findings at a South African forensic pathology laboratory in cases of sudden unexpected death in infants

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Naomi Fenton-Muir

2012-02-01

Full Text Available Objectives The work serves as a preliminary evaluation of the utility of the full-body radiography in examining cases of SUDI. Setting This paper reviews findings from full-body digital radiography in cases of sudden unexpected death in infants (SUDI in 2008 at the Salt River Forensic Pathology Laboratory in Cape Town. Subjects Cases of SUDI referred to the mortuary and undergoing full-body digital radiography were reviewed (192 cases. Design Imaging reports were cross-referenced with death registry data. Manner of death, cause of death, whether an autopsy had taken place, and radiological findings, were recorded and analysed. Results The absence of bony fractures was recorded as an imaging finding in 40% of cases. The most common type of imaging pathology was lung disease. In cases where autopsies were performed and pathology was found on imaging, the findings of the two methods of examination were consistent. Conclusions Imaging may have served to assist CoD determination based on case history, and therefore full-body radiography may improve the workflow in busy forensic pathology laboratories. More detailed and consistent recording of imaging findings is required before stronger conclusions may be drawn regarding the utility of full body digital imaging of paediatric cases in forensic pathology laboratories.

Eclalbasaponin II induces autophagic and apoptotic cell death in human ovarian cancer cells

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Yoon Jin Cho

2016-09-01

Full Text Available Triterpenoids echinocystic acid and its glycosides, isolated from several Eclipta prostrata, have been reported to possess various biological activities such as anti-inflammatory, anti-bacterial, and anti-diabetic activity. However, the cytotoxicity of the triterpenoids in human cancer cells and their molecular mechanism of action are poorly understood. In the present study, we found that eclalbasaponin II with one glucose moiety has potent cytotoxicity in three ovarian cancer cells and two endometrial cancer cells compared to an aglycone echinocystic acid and eclalbasaponin I with two glucose moiety. Eclalbasaponin II treatment dose-dependently increased sub G1 population. Annexin V staining revealed that eclalbasaponin II induced apoptosis in SKOV3 and A2780 ovarian cancer cells. In addition, eclalbasaponin II-induced cell death was associated with characteristics of autophagy; an increase in acidic vesicular organelle content and elevation of the levels of LC3-II. Interestingly, autophagy inhibitor BaF1 suppressed the eclalbasaponin II-induced apoptosis. Moreover, eclalbasaponin II activated JNK and p38 signaling and inhibited the mTOR signaling. We further demonstrated that pre-treatment with a JNK and p38 inhibitor and mTOR activator attenuated the eclalbasaponin II-induced autophagy. This suggests that eclalbasaponin II induces apoptotic and autophagic cell death through the regulation of JNK, p38, and mTOR signaling in human ovarian cancer cells.

Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells.

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Scarlatti, F; Maffei, R; Beau, I; Codogno, P; Ghidoni, R

2008-08-01

Resveratrol, a polyphenol found in grapes and other fruit and vegetables, is a powerful chemopreventive and chemotherapeutic molecule potentially of interest for the treatment of breast cancer. The human breast cancer cell line MCF-7, which is devoid of caspase-3 activity, is refractory to apoptotic cell death after incubation with resveratrol. Here we show that resveratrol arrests cell proliferation, triggers death and decreases the number of colonies of cells that are sensitive to caspase-3-dependent apoptosis (MCF-7 casp-3) and also those that are unresponsive to it (MCF-7vc). We demonstrate that resveratrol (i) acts via multiple pathways to trigger cell death, (ii) induces caspase-dependent and caspase-independent cell death in MCF-7 casp-3 cells, (iii) induces only caspase-independent cell death in MCF-7vc cells and (iv) stimulates macroautophagy. Using BECN1 and hVPS34 (human vacuolar protein sorting 34) small interfering RNAs, we demonstrate that resveratrol activates Beclin 1-independent autophagy in both cell lines, whereas cell death via this uncommon form of autophagy occurs only in MCF-7vc cells. We also show that this variant form of autophagic cell death is blocked by the expression of caspase-3, but not by its enzymatic activity. In conclusion, this study reveals that non-canonical autophagy induced by resveratrol can act as a caspase-independent cell death mechanism in breast cancer cells.

Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis.

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Janssen-Heijnen, M L G; van Erning, F N; De Ruysscher, D K; Coebergh, J W W; Groen, H J M

2015-05-01

Many patients with non-small cell lung cancer (NSCLC) die within the first few years of diagnosis, and considerable excess mortality remains even after 5 years. We investigated the death rate and the distribution of causes of death for NSCLC patients by age and stage at diagnosis during long-term follow-up. All 72 021 patients aged 45-89 years diagnosed with stage I-III NSCLC between 1989 and 2008 in the Netherlands and who died up till 2011 were derived from the Netherlands Cancer Registry and linked with the database of Statistics Netherlands for underlying causes of death. Mortality ratios and proportional distribution of causes of death were calculated during 5 time periods after diagnosis of NSCLC (up to 15 years). Median follow-up was 9.6 years (range: 0-23 years). Lung cancer was the predominant cause of death in the first 6 years after diagnosis (being 80%-85% and ∼90% up to 3 years for localized and locally advanced disease, respectively, and ∼60%-75% and ∼75%-85% during years 4-6 for both stage groups, respectively). Thereafter, lung cancer as cause of death proportionally decreased with time since diagnosis, but remained over 30%. Hence, cardiovascular diseases and chronic obstructive pulmonary diseases (COPD) became more important causes of death, especially for patients aged >60 years at diagnosis (up to 34% for cardiovascular diseases and up to 19% for COPD). With time, the relative contribution of cardiovascular and COPD causes of death increased, although the absolute contribution of lung cancer remained high in non-metastatic NSCLC. Therefore, managing morbidity of these diseases remains relevant. © The Author 2015. 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.

Cancer mortality and other causes of death in users of geothermal hot water.

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Kristbjornsdottir, Adalbjorg; Rafnsson, Vilhjalmur

2015-01-01

Residents of geothermal areas have increased incidence of non-Hodgkin's lymphoma, breast, prostate, and kidney cancers. The aim was to study whether this is also reflected in cancer mortality among the population using geothermal hot water for space heating, washing, and showering. The follow-up was from 1981 to 2009. Personal identifier of those 5-64 years of age was used in record linkage with nationwide death registry. Thus, vital and emigration status was ascertained. The exposed population was defined as inhabitants of communities with district heating generated from geothermal wells since 1972. Reference populations were inhabitants of other areas with different degrees of volcanic/geothermal activity. Hazard ratio (HR) and 95% confidence intervals (CI) were adjusted for age, gender, education, housing, reproductive factors and smoking habits. Among those using geothermal water, the HR for all causes of death was 0.98 (95% CI 0.91-1.05) as compared with cold reference area. The HR for breast cancer was 1.53 (1.04-2.24), prostate cancer 1.74 (1.21-2.52), kidney cancer 1.78 (1.03-3.07), and for non-Hodgkin's lymphoma 2.01 (1.05-3.38). HR for influenza was 3.36 (1.32-8.58) and for suicide 1.49 (1.03-2.17). The significant excess mortality risk of breast and prostate cancers, and non-Hodgkin's lymphoma confirmed the results of similarly designed studies in Iceland on cancer incidence among populations from high-temperature geothermal areas and users of geothermal hot water. The risk is not confined to cancers with good prognosis, but also concerns fatal cancers. Further studies are needed on the chemical and physical content of the water and the environment emissions in geothermal areas.

Targeted cancer cell death induced by biofunctionalized magnetic nanowires

KAUST Repository

Contreras, Maria F.; Ravasi, Timothy; Kosel, Jü rgen

2014-01-01

Magnetic micro and nanomaterials are increasingly interesting for biomedical applications since they possess many advantageous properties: they can become biocompatible, they can be functionalized to target specific cells and they can be remotely manipulated by magnetic fields. The goal of this study is to use antibody-functionalized nickel nanowires (Ab-NWs) as an alternative method in cancer therapy overcoming the limitations of current treatments that lack specificity and are highly cytotoxic. Ab-NWs have been incubated with cancer cells and a 12% drop on cell viability was observed for a treatment of only 10 minutes and an alternating magnetic field of low intensity and low frequency. It is believed that the Ab-NWs vibrate transmitting a mechanical force to the targeted cells inducing cell death. © 2014 IEEE.

Targeted cancer cell death induced by biofunctionalized magnetic nanowires

KAUST Repository

Contreras, Maria F.

2014-02-01

Magnetic micro and nanomaterials are increasingly interesting for biomedical applications since they possess many advantageous properties: they can become biocompatible, they can be functionalized to target specific cells and they can be remotely manipulated by magnetic fields. The goal of this study is to use antibody-functionalized nickel nanowires (Ab-NWs) as an alternative method in cancer therapy overcoming the limitations of current treatments that lack specificity and are highly cytotoxic. Ab-NWs have been incubated with cancer cells and a 12% drop on cell viability was observed for a treatment of only 10 minutes and an alternating magnetic field of low intensity and low frequency. It is believed that the Ab-NWs vibrate transmitting a mechanical force to the targeted cells inducing cell death. © 2014 IEEE.

Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-Bromopyruvate

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Chen, Zhao; Zhang, Hui; Lu, Weiqin; Huang, Peng

2009-01-01

Summary It has long been observed that cancer cells rely more on glycolysis to generate ATP and actively use certain glycolytic metabolic intermediates for biosynthesis. Hexokinase II (HKII) is a key glycolytic enzyme that plays a role in the regulation of the mitochondria-initiated apoptotic cell death. As a potent inhibitor of hexokinase, 3-bromopyruvate (3-BrPA) is known to inhibit cancer cell energy metabolism and trigger cell death, supposedly through depletion of cellular ATP. The current study showed that 3-BrPA caused a covalent modification of HKII protein and directly triggered its dissociation from mitochondria, leading to a specific release of apoptosis-inducing factor (AIF) from the mitochondria to cytosol and eventual cell death. Co-immunoprecipitation revealed a physical interaction between HKII and AIF. Using a competitive peptide of HKII, we showed that the dissociation of hexokinase II from mitochondria alone could cause apoptotic cell death, especially in the mitochondria-deficient ρ0 cells that highly express HKII. Interestingly, the dissociation of HKII itself did no directly affect the mitochondrial membrane potential, ROS generation, and oxidative phosphorylation. Our study suggests that the physical association between HKII and AIF is important for the normal localization of AIF in the mitochondria, and disruption of this protein complex by 3-BrPA leads to their release from the mitochondria and eventual cell death. PMID:19285479

Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway.

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Jo, Miran; Park, Mi Hee; Kollipara, Pushpa Saranya; An, Byeong Jun; Song, Ho Sueb; Han, Sang Bae; Kim, Jang Heub; Song, Min Jong; Hong, Jin Tae

2012-01-01

We investigated whether bee venom and melittin, a major component of bee venom, inhibit cell growth through enhancement of death receptor expressions in the human ovarian cancer cells, SKOV3 and PA-1. Bee venom (1-5 μg/ml) and melittin (0.5-2 μg/ml) inhibited the growth of SKOV3 and PA-1 ovarian cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of death receptor (DR) 3 and DR6 was increased in both cancer cells, but expression of DR4 was increased only in PA-1 cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, 8, and Bax was concomitantly increased, but the phosphorylation of JAK2 and STAT3 and the expression of Bcl-2 were inhibited by treatment with bee venom and melittin in SKOV3 and PA-1 cells. Expression of cleaved caspase-3 was increased in SKOV3, but cleaved caspase-8 was increased in PA-1 cells. Moreover, deletion of DR3, DR4, and DR6 by small interfering RNA significantly reversed bee venom and melittin-induced cell growth inhibitory effect as well as down regulation of STAT3 by bee venom and melittin in SKOV3 and PA-1 ovarian cancer cell. These results suggest that bee venom and melittin induce apoptotic cell death in ovarian cancer cells through enhancement of DR3, DR4, and DR6 expression and inhibition of STAT3 pathway. Copyright © 2011 Elsevier Inc. All rights reserved.

Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

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Joo, Ijin [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of); Kim, Haeryoung [Department of Pathology, Seoul National University Bundang Hospital, Seongnam 463-707 (Korea, Republic of); Lee, Jeong Min [Department of Radiology, Seoul National University Hospital, Seoul 110-744 (Korea, Republic of)

2015-11-01

There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients.

Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

International Nuclear Information System (INIS)

Joo, Ijin; Kim, Haeryoung; Lee, Jeong Min

2015-01-01

There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients

Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism

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Gorbunova, Vera; Hine, Christopher; Tian, Xiao; Ablaeva, Julia; Gudkov, Andrei V.; Nevo, Eviatar; Seluanov, Andrei

2012-01-01

Blind mole rats Spalax (BMR) are small subterranean rodents common in the Middle East. BMR is distinguished by its adaptations to life underground, remarkable longevity (with a maximum documented lifespan of 21 y), and resistance to cancer. Spontaneous tumors have never been observed in spalacids. To understand the mechanisms responsible for this resistance, we examined the growth of BMR fibroblasts in vitro of the species Spalax judaei and Spalax golani. BMR cells proliferated actively for 7–20 population doublings, after which the cells began secreting IFN-β, and the cultures underwent massive necrotic cell death within 3 d. The necrotic cell death phenomenon was independent of culture conditions or telomere shortening. Interestingly, this cell behavior was distinct from that observed in another long-lived and cancer-resistant African mole rat, Heterocephalus glaber, the naked mole rat in which cells display hypersensitivity to contact inhibition. Sequestration of p53 and Rb proteins using SV40 large T antigen completely rescued necrotic cell death. Our results suggest that cancer resistance of BMR is conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways, and triggered by the release of IFN-β. Thus, we have identified a unique mechanism that contributes to cancer resistance of this subterranean mammal extremely adapted to life underground. PMID:23129611

A Case-Control Study to Estimate the Impact of the Icelandic Population-Based Mammography Screening Program on Breast Cancer Death

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Gabe, R.; Tryggvadottir, L.; Sigfusson, B.F.; Olafsdottir, G.H.; Sigurarsson , K. [Icelandic Cancer Society (Krabbameinsfelag Islands), Reykjavik (Iceland); Duffy, S.W. [Cancer Research UK, Centre for Epidemiology, Mathematics and Stati stics, Wolfson Inst. of Preventive Medicine, London (United Kingdom)

2007-11-15

Background: The Icelandic breast cancer screening program, initiated November 1987 in Reykjavik and covering the whole country from December 1989, comprises biennial invitation to mammography for women aged 40-69 years old. Purpose: To estimate the impact of mammography service screening in Iceland on deaths from breast cancer. Material and Methods: Cases were deaths from breast cancer from 1990 onwards in women aged 40 and over at diagnosis, during the period November 1987 to December 31, 2002. Age- and screening-area-matched, population-based controls were women who had also been invited to screening but were alive at the time their case died. Results: Using conditional logistic regression on the data from 226 cases and 902 controls, the odds ratio for the risk of death from breast cancer in those attending at least one screen compared to those never screened was 0.59 (95% CI 0.41-0.84). After adjustment for healthy-volunteer bias and screening-opportunity bias, the odds ratio was 0.65 (95% CI 0.39-1.09). Conclusion: These results indicate a 35-40% reduction in breast cancer deaths by attending the Icelandic breast cancer screening program. These results are consistent with the overall evidence from other observational evaluations of mammography-based programs.

A Case-Control Study to Estimate the Impact of the Icelandic Population-Based Mammography Screening Program on Breast Cancer Death

International Nuclear Information System (INIS)

Gabe, R.; Tryggvadottir, L.; Sigfusson, B.F.; Olafsdottir, G.H.; Sigurarsson, K.; Duffy, S.W.

2007-01-01

Background: The Icelandic breast cancer screening program, initiated November 1987 in Reykjavik and covering the whole country from December 1989, comprises biennial invitation to mammography for women aged 40-69 years old. Purpose: To estimate the impact of mammography service screening in Iceland on deaths from breast cancer. Material and Methods: Cases were deaths from breast cancer from 1990 onwards in women aged 40 and over at diagnosis, during the period November 1987 to December 31, 2002. Age- and screening-area-matched, population-based controls were women who had also been invited to screening but were alive at the time their case died. Results: Using conditional logistic regression on the data from 226 cases and 902 controls, the odds ratio for the risk of death from breast cancer in those attending at least one screen compared to those never screened was 0.59 (95% CI 0.41-0.84). After adjustment for healthy-volunteer bias and screening-opportunity bias, the odds ratio was 0.65 (95% CI 0.39-1.09). Conclusion: These results indicate a 35-40% reduction in breast cancer deaths by attending the Icelandic breast cancer screening program. These results are consistent with the overall evidence from other observational evaluations of mammography-based programs

Annonaceous acetogenin mimic AA005 induces cancer cell death via apoptosis inducing factor through a caspase-3-independent mechanism.

Science.gov (United States)

Han, Bing; Wang, Tong-Dan; Shen, Shao-Ming; Yu, Yun; Mao, Chan; Yao, Zhu-Jun; Wang, Li-Shun

2015-03-18

Annonaceous acetogenins are a family of natural products with antitumor activities. Annonaceous acetogenin mimic AA005 reportedly inhibits mammalian mitochondrial NADH-ubiquinone reductase (Complex I) and induces gastric cancer cell death. However, the mechanisms underlying its cell-death-inducing activity are unclear. We used SW620 colorectal adenocarcinoma cells to study AA005 cytotoxic activity. Cell deaths were determined by Trypan blue assay and flow cytometry, and related proteins were characterized by western blot. Immunofluorescence and subcellular fractionation were used to evaluate AIF nuclear translocation. Reactive oxygen species were assessed by using redox-sensitive dye DCFDA. AA005 induces a unique type of cell death in colorectal adenocarcinoma cells, characterized by lack of caspase-3 activation or apoptotic body formation, sensitivity to poly (ADP-ribose) polymerase inhibitor Olaparib (AZD2281) but not pan-caspase inhibitor Z-VAD.fmk, and dependence on apoptosis-inducing factor (AIF). AA005 treatment also reduced expression of mitochondrial Complex I components, and leads to accumulation of intracellular reactive oxygen species (ROS) at the early stage. Blocking ROS formation significantly suppresses AA005-induced cell death in SW620 cells. Moreover, blocking activation of RIP-1 by necroptosis inhibitor necrotatin-1 inhibits AIF translocation and partially suppresses AA005-induced cell death in SW620 cells demonstrating that RIP-1 protein may be essential for cell death. AA005 may trigger the cell death via mediated by AIF through caspase-3 independent pathway. Our work provided new mechanisms for AA005-induced cancer cell death and novel clues for cancer treatment via AIF dependent cell death.

Comparing verbal autopsy cause of death findings as determined by physician coding and probabilistic modelling: a public health analysis of 54 000 deaths in Africa and Asia

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Peter Byass

2015-06-01

Full Text Available Background: Coverage of civil registration and vital statistics varies globally, with most deaths in Africa and Asia remaining either unregistered or registered without cause of death. One important constraint has been a lack of fit–for–purpose tools for registering deaths and assigning causes in situations where no doctor is involved. Verbal autopsy (interviewing care–givers and witnesses to deaths and interpreting their information into causes of death is the only available solution. Automated interpretation of verbal autopsy data into cause of death information is essential for rapid, consistent and affordable processing. Methods: Verbal autopsy archives covering 54182 deaths from five African and Asian countries were sourced on the basis of their geographical, epidemiological and methodological diversity, with existing physician–coded causes of death attributed. These data were unified into the WHO 2012 verbal autopsy standard format, and processed using the InterVA–4 model. Cause–specific mortality fractions from InterVA–4 and physician codes were calculated for each of 60 WHO 2012 cause categories, by age group, sex and source. Results from the two approaches were assessed for concordance and ratios of fractions by cause category. As an alternative metric, the Wilcoxon matched–pairs signed ranks test with two one–sided tests for stochastic equivalence was used. Findings: The overall concordance correlation coefficient between InterVA–4 and physician codes was 0.83 (95% CI 0.75 to 0.91 and this increased to 0.97 (95% CI 0.96 to 0.99 when HIV/AIDS and pulmonary TB deaths were combined into a single category. Over half (53% of the cause category ratios between InterVA–4 and physician codes by source were not significantly different from unity at the 99% level, increasing to 62% by age group. Wilcoxon tests for stochastic equivalence also demonstrated equivalence. Conclusions: These findings show strong concordance

Cases study of lung cancer deaths and analysis of radon levels in house-room of Mexicali, B. C

International Nuclear Information System (INIS)

Lopez B, G.; Reyna C, M. A.

2009-10-01

The lung cancer is a case of health of more importance as much in women as in men, with more frequency that the cancer of mamma, colon and prostate on the whole. A factor that influences in the cancer generation originating serious complications it is the exposition to radioactive substances in closed places, as house-room. In the investigation study, levels of radon concentration were measured in interiors of Mexicali homes, to study the relationship that this gas could have with the death cases by lung cancer into population. The gas radon is radioactive and it adheres easily to particles that remain suspended in air; when inhaling them small explosions take place inside the alveoli, changing the DNA of cells and lung cancer is generated. The meteorological, geographical and urban characteristics of Mexicali, favor conditions so that certain areas of the city present high indexes of suspended particles in atmosphere. One sample of gas radon inside 100 house-rooms, the analysis was made by paved and not paved colonies and for sex, to establish if the death cases by lung cancer had relationship with the genus and/or with some of two groups of colonies. The study found that the major number of deaths it was presented in colonies in which lacked the paving service and always happened with more frequency in women; and that in homes of having died by lung cancer the radon concentrations were more high that the homes where there was not death cases, with significant differences that go from 9.2% to 70%. This investigation project is presented as a cases study in the Mexicali City. (Author)

Dendritic Cells and Programmed Death-1 Blockade: A Joint Venture to Combat Cancer.

Science.gov (United States)

Versteven, Maarten; Van den Bergh, Johan M J; Marcq, Elly; Smits, Evelien L J; Van Tendeloo, Viggo F I; Hobo, Willemijn; Lion, Eva

2018-01-01

Two decades of clinical cancer research with dendritic cell (DC)-based vaccination have proved that this type of personalized medicine is safe and has the capacity to improve survival, but monotherapy is unlikely to cure the cancer. Designed to empower the patient's antitumor immunity, huge research efforts are set to improve the efficacy of next-generation DC vaccines and to find synergistic combinations with existing cancer therapies. Immune checkpoint approaches, aiming to breach immune suppression and evasion to reinforce antitumor immunity, have been a revelation in the immunotherapy field. Early success of therapeutic antibodies blocking the programmed death-1 (PD-1) pathway has sparked the development of novel inhibitors and combination therapies. Hence, merging immunoregulatory tumor-specific DC strategies with PD-1-targeted approaches is a promising path to explore. In this review, we focus on the role of PD-1-signaling in DC-mediated antitumor immunity. In the quest of exploiting the full potential of DC therapy, different strategies to leverage DC immunopotency by impeding PD-1-mediated immune regulation are discussed, including the most advanced research on targeted therapeutic antibodies, lessons learned from chemotherapy-induced immune activation, and more recent developments with soluble molecules and gene-silencing techniques. An overview of DC/PD-1 immunotherapy combinations that are currently under preclinical and clinical investigation substantiates the clinical potential of such combination strategies.

Calix[6]arene bypasses human pancreatic cancer aggressiveness: downregulation of receptor tyrosine kinases and induction of cell death by reticulum stress and autophagy.

Science.gov (United States)

Pelizzaro-Rocha, Karin Juliane; de Jesus, Marcelo Bispo; Ruela-de-Sousa, Roberta Regina; Nakamura, Celso Vataru; Reis, Fabiano Souza; de Fátima, Angelo; Ferreira-Halder, Carmen Veríssima

2013-12-01

Pancreatic cancer ranks fourth among cancer-related causes of death in North America. Minimal progress has been made in the diagnosis and treatment of patients with late-stage tumors. Moreover, pancreatic cancer aggressiveness is closely related to high levels of pro-survival mediators, which can ultimately lead to rapid disease progression, resistance and metastasis. The main goal of this study was to define the mechanisms by which calix[6]arene, but not other calixarenes, efficiently decreases the aggressiveness of a drug resistant human pancreas carcinoma cell line (Panc-1). Calix[6]arene was more potent in reducing Panc-1 cell viability than gemcitabine and 5-fluorouracil. In relation to the underlying mechanisms of cytotoxic effects, it led to cell cycle arrest in the G0/G1 phase through downregulation of PIM1, CDK2, CDK4 and retinoblastoma proteins. Importantly, calix[6]arene abolished signal transduction of Mer and AXL tyrosine kinase receptors, both of which are usually overexpressed in pancreatic cancer. Accordingly, inhibition of PI3K and mTOR was also observed, and these proteins are positively modulated by Mer and AXL. Despite decreasing the phosphorylation of AKT at Thr308, calix[6]arene caused an increase in phosphorylation at Ser473. These findings in conjunction with increased BiP and IRE1-α provide a molecular basis explaining the capacity of calix[6]arene to trigger endoplasmic reticulum stress and autophagic cell death. Our findings highlight calix[6]arene as a potential candidate for overcoming pancreatic cancer aggressiveness. Importantly, we provide evidence that calix[6]arene affects a broad array of key targets that are usually dysfunctional in pancreatic cancer, a highly desirable characteristic for chemotherapeutics. © 2013.

Psychological process from hospitalization to death among uninformed terminal liver cancer patients in Japan

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Kobori Eiko

2006-09-01

Full Text Available Abstract Background Although the attitude among doctors toward disclosing a cancer diagnosis is becoming more positive, informing patients of their disease has not yet become a common practice in Japan. We examined the psychological process, from hospitalization until death, among uninformed terminal cancer patients in Japan, and developed a psychological model. Methods Terminal cancer patients hospitalized during the recruiting period voluntarily participated in in-depth interviews. The data were analyzed by grounded theory. Results Of the 87 uninformed participants at the time of hospitalization, 67% (N = 59 died without being informed of their diagnosis. All were male, 51–66 years of age, and all experienced five psychological stages: anxiety and puzzlement, suspicion and denial, certainty, preparation, and acceptance. At the end of each stage, obvious and severe feelings were observed, which were called "gates." During the final acceptance stage, patients spent a peaceful time with family, even talking about their dreams with family members. Conclusion Unlike in other studies, the uninformed patients in this study accepted death peacefully, with no exceptional cases. Despite several limitations, this study showed that almost 70% of the uninformed terminal cancer patients at hospitalization died without being informed, suggesting an urgent need for culturally specific and effective terminal care services for cancer patients in Japan.

Genistein cooperates with the histone deacetylase inhibitor vorinostat to induce cell death in prostate cancer cells

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Phillip Cornel J

2012-04-01

Full Text Available Abstract Background Among American men, prostate cancer is the most common, non-cutaneous malignancy that accounted for an estimated 241,000 new cases and 34,000 deaths in 2011. Previous studies have suggested that Wnt pathway inhibitory genes are silenced by CpG hypermethylation, and other studies have suggested that genistein can demethylate hypermethylated DNA. Genistein is a soy isoflavone with diverse effects on cellular proliferation, survival, and gene expression that suggest it could be a potential therapeutic agent for prostate cancer. We undertook the present study to investigate the effects of genistein on the epigenome of prostate cancer cells and to discover novel combination approaches of other compounds with genistein that might be of translational utility. Here, we have investigated the effects of genistein on several prostate cancer cell lines, including the ARCaP-E/ARCaP-M model of the epithelial to mesenchymal transition (EMT, to analyze effects on their epigenetic state. In addition, we investigated the effects of combined treatment of genistein with the histone deacetylase inhibitor vorinostat on survival in prostate cancer cells. Methods Using whole genome expression profiling and whole genome methylation profiling, we have determined the genome-wide differences in genetic and epigenetic responses to genistein in prostate cancer cells before and after undergoing the EMT. Also, cells were treated with genistein, vorinostat, and combination treatment, where cell death and cell proliferation was determined. Results Contrary to earlier reports, genistein did not have an effect on CpG methylation at 20 μM, but it did affect histone H3K9 acetylation and induced increased expression of histone acetyltransferase 1 (HAT1. In addition, genistein also had differential effects on survival and cooperated with the histone deacteylase inhibitor vorinostat to induce cell death and inhibit proliferation. Conclusion Our results suggest that

Murraya koenigii leaf extract inhibits proteasome activity and induces cell death in breast cancer cells

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Noolu Bindu

2013-01-01

Full Text Available Abstract Background Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, polyphenols/flavonoids have been reported to inhibit proteasome activity. Murraya koenigii Spreng, a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine. Here we show that Murraya koenigii leaves (curry leaves, a rich source of polyphenols, inhibit the proteolytic activity of the cancer cell proteasome, and cause cell death. Methods Hydro-methanolic extract of curry leaves (CLE was prepared and its total phenolic content [TPC] determined by, the Folin-Ciocalteau’s method. Two human breast carcinoma cell lines: MCF-7 and MDA-MB-231 and a normal human lung fibroblast cell line, WI-38 were used for the studies. Cytotoxicity of the CLE was assessed by the MTT assay. We studied the effect of CLE on growth kinetics using colony formation assay. Growth arrest was assessed by cell cycle analysis and apoptosis by Annexin-V binding using flow cytometry. Inhibition of the endogenous 26S proteasome was studied in intact cells and cell extracts using substrates specific to 20S proteasomal enzymes. Results CLE decreased cell viability and altered the growth kinetics in both the breast cancer cell lines in a dose-dependent manner. It showed a significant arrest of cells in the S phase albeit in cancer cells only. Annexin V binding data suggests that cell death was via the apoptotic pathway in both the cancer cell lines. CLE treatment significantly decreased the activity of the 26S proteasome in the cancer but not normal cells. Conclusions Our study suggests M. koenigii leaves to be a potent source of proteasome inhibitors that lead to cancer cell death

Low-frequency quantitative ultrasound imaging of cell death in vivo

International Nuclear Information System (INIS)

Sadeghi-Naini, Ali; Falou, Omar; Czarnota, Gregory J.; Papanicolau, Naum; Tadayyon, Hadi; Lee, Justin; Zubovits, Judit; Sadeghian, Alireza; Karshafian, Raffi; Al-Mahrouki, Azza; Giles, Anoja; Kolios, Michael C.

2013-01-01

Purpose: Currently, no clinical imaging modality is used routinely to assess tumor response to cancer therapies within hours to days of the delivery of treatment. Here, the authors demonstrate the efficacy of ultrasound at a clinically relevant frequency to quantitatively detect changes in tumors in response to cancer therapies using preclinical mouse models.Methods: Conventional low-frequency and corresponding high-frequency ultrasound (ranging from 4 to 28 MHz) were used along with quantitative spectroscopic and signal envelope statistical analyses on data obtained from xenograft tumors treated with chemotherapy, x-ray radiation, as well as a novel vascular targeting microbubble therapy.Results: Ultrasound-based spectroscopic biomarkers indicated significant changes in cell-death associated parameters in responsive tumors. Specifically changes in the midband fit, spectral slope, and 0-MHz intercept biomarkers were investigated for different types of treatment and demonstrated cell-death related changes. The midband fit and 0-MHz intercept biomarker derived from low-frequency data demonstrated increases ranging approximately from 0 to 6 dBr and 0 to 8 dBr, respectively, depending on treatments administrated. These data paralleled results observed for high-frequency ultrasound data. Statistical analysis of ultrasound signal envelope was performed as an alternative method to obtain histogram-based biomarkers and provided confirmatory results. Histological analysis of tumor specimens indicated up to 61% cell death present in the tumors depending on treatments administered, consistent with quantitative ultrasound findings indicating cell death. Ultrasound-based spectroscopic biomarkers demonstrated a good correlation with histological morphological findings indicative of cell death (r 2 = 0.71, 0.82; p < 0.001).Conclusions: In summary, the results provide preclinical evidence, for the first time, that quantitative ultrasound used at a clinically relevant frequency, in

Low-frequency quantitative ultrasound imaging of cell death in vivo

Energy Technology Data Exchange (ETDEWEB)

Sadeghi-Naini, Ali; Falou, Omar; Czarnota, Gregory J. [Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Papanicolau, Naum; Tadayyon, Hadi [Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Lee, Justin [Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5 (Canada); Zubovits, Judit [Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Sadeghian, Alireza [Department of Computer Science, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Karshafian, Raffi [Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada); Al-Mahrouki, Azza; Giles, Anoja [Imaging Research – Physical Science, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada and Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5 (Canada); Kolios, Michael C. [Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario M4N 3M5, Canada and Department of Physics, Ryerson University, Toronto, Ontario M5B 2K3 (Canada)

2013-08-15

Purpose: Currently, no clinical imaging modality is used routinely to assess tumor response to cancer therapies within hours to days of the delivery of treatment. Here, the authors demonstrate the efficacy of ultrasound at a clinically relevant frequency to quantitatively detect changes in tumors in response to cancer therapies using preclinical mouse models.Methods: Conventional low-frequency and corresponding high-frequency ultrasound (ranging from 4 to 28 MHz) were used along with quantitative spectroscopic and signal envelope statistical analyses on data obtained from xenograft tumors treated with chemotherapy, x-ray radiation, as well as a novel vascular targeting microbubble therapy.Results: Ultrasound-based spectroscopic biomarkers indicated significant changes in cell-death associated parameters in responsive tumors. Specifically changes in the midband fit, spectral slope, and 0-MHz intercept biomarkers were investigated for different types of treatment and demonstrated cell-death related changes. The midband fit and 0-MHz intercept biomarker derived from low-frequency data demonstrated increases ranging approximately from 0 to 6 dBr and 0 to 8 dBr, respectively, depending on treatments administrated. These data paralleled results observed for high-frequency ultrasound data. Statistical analysis of ultrasound signal envelope was performed as an alternative method to obtain histogram-based biomarkers and provided confirmatory results. Histological analysis of tumor specimens indicated up to 61% cell death present in the tumors depending on treatments administered, consistent with quantitative ultrasound findings indicating cell death. Ultrasound-based spectroscopic biomarkers demonstrated a good correlation with histological morphological findings indicative of cell death (r{sup 2}= 0.71, 0.82; p < 0.001).Conclusions: In summary, the results provide preclinical evidence, for the first time, that quantitative ultrasound used at a clinically relevant frequency

Causes of death in long-term survivors of non-small cell lung cancer: A regional Surveillance, Epidemiology, and End Results study.

Science.gov (United States)

Kanitkar, Amaraja A; Schwartz, Ann G; George, Julie; Soubani, Ayman O

2018-01-01

Survival from lung cancer is improving. There are limited data on the causes of death in 5-year survivors of lung cancer. The aim of this study is to explore the causes of death in long-term survivors of non-small cell lung cancer (NSCLC) and describe the odds of dying from causes other than lung cancer in this patient population. An analysis of 5-year survivors of newly diagnosed NSCLC from 1996 to 2007, in Metropolitan Detroit included in Surveillance, Epidemiology, and End Results program, was done. Of 23,059 patients identified, 3789 (16.43%) patients were alive at 5-year period (long-term survivors) and 1897 (50.06%) patients died in the later follow-up period (median 88 months; range 1-219 months). The causes of death besides lung cancer were observed in 55.2% of these patients. The most common causes of death were cardiovascular diseases (CVDs) (16%), chronic obstructive pulmonary diseases (11%), and other malignancies (8%). Patients older than 65 years, males, and those who underwent surgery for treatment of lung cancer faced a greater likelihood of death by other causes as compared to lung cancer (OR: 1.45, 95% confidence interval [CI]: 1.18-1.77; OR: 1.24, 95% CI: 1.02-1.51; and OR: 1.39, 95% CI: 1.06-1.82, respectively). Five-year survivors of NSCLC more commonly die from causes such as CVDs, lung diseases, and other malignancies. Aggressive preventive and therapeutic measures of these diseases may further improve the outcome in this patient population.

Analysis of mammographic findings of breast cancer

International Nuclear Information System (INIS)

Park, Hyun Joo; Han, Heon; Yang, Dal Mo; Chung, Hyo Sun; Kim, Jee Eun; Kim, Young Chae

1995-01-01

This study is to describe authors' experience on mammographic findings of breast cancer and to know if there is difference between 35 years of age or younger and older groups. Mammograms of 72 patients with breast cancer detected from January, 1991 to December, 1993 were retrospectively analysed. Mammographic findings were classified into mass only, mass with microcalcifications, microcalcifications only and others. Marginal characteristics of mass were classified into spiculated, poorly marginated and well marginated. Shape of microcalcifications were classified into casting, granular and mixed types. These findings were compared between 35 years of age or younger and older groups. Mammogram showed mass only in 33 patients (46%), mass with microcalcifications in 26 patients (36%), microcalcifications only in seven (10%) and other findings in six (8%). Other findings were architectural distortion, asymmetric high density and incidental breast carcinoma from paraffinoma in one patient respectively, and dense breast in three patients. The margins of the breast mass were spiculated in ten (17%). poorly marginated in 30 (51%), well-marginated in 19 (32%). Shape of microcalcifications were casting type in 13 (40%). granular in 14 (42%) and mixed in six (18%) cases. 3 patients had dense breast with which mammography did not demonstrate the lesion. 3 patients without mammographically demonstrable lesions due to dense breasts were under 35 years in age, and there was statistically significant difference between the two groups (ρ -value < 0.05). Microcalcifications only was more common findings in 35 years of age or younger. The most important mammographic findings of breast cancer were mass and microcalcifications. Architectural distortion and asymmetric high density were additional findings. In 35 years of age or younger, microcalcifications only was an important finding because mass lesions are frequently masked by dense breast. Thus other imaging modalities, such as

Indicative findings of pancreatic cancer in prediagnostic CT

International Nuclear Information System (INIS)

Ahn, Sung Soo; Choi, Jin-Young; Hong, Hye-Suk; Chung, Yong Eun; Lim, Joon Seok; Kim, Myeong-Jin

2009-01-01

We examined 20 prediagnostic CTs from 16 patients for whom the diagnosis of pancreatic cancer was delayed until full diagnostic CT was performed. Three radiologists independently reviewed the prediagnostic CTs along with 50 CTs of control subjects, including patients without pancreatic disease (n = 38) or with chronic pancreatitis without calcification visible on CT (n=12). The reviewers recorded the presence of biliary or pancreatic ductal dilation, interruption of the pancreatic duct, distal parenchymal atrophy, contour abnormality and focal hypoattenuation. Frequency, sensitivity and specificity of the significant findings were calculated. Logistic regression analysis was performed. Findings indicative of pancreatic cancer were seen on 85% (17/20) of the prediagnostic CTs. Patients with pancreatic cancer were significantly (p<0.05) more likely to show focal hypoattenuation, pancreatic duct dilation, interruption of the pancreatic duct, and distal parenchymal atrophy, with sensitivities and specificities of 75%/84%, 50%/78%, 45%/82% and 45%/96%, respectively. Focal hypoattenuation and distal parenchymal atrophy were the independent predictors of pancreatic cancer with odds ratios of 20.92 and 11.22, respectively. In conclusion, focal hypoattenuation and pancreatic duct dilation with or without interruption, especially when accompanied by distal parenchymal atrophy, were the most useful findings for avoiding delayed diagnosis of pancreatic cancer. (orig.)

Non-Steroidal Anti-Inflammatory Drugs and Cancer Death in the Finnish Prostate Cancer Screening Trial.

Directory of Open Access Journals (Sweden)

Thea Veitonmäki

Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs, especially aspirin, have been associated with lowered cancer incidence and mortality. We examined overall cancer mortality and mortality from specific cancer sites among the 80,144 men in the Finnish Prostate Cancer Screening Trial. Information on prescription drug use was acquired from the national drug reimbursement database. Over-the-counter use information was gathered by a questionnaire. Hazard ratios (HR and 95% confidence intervals (CI by prescription and over-the-counter NSAID use for overall and specific cancer deaths were calculated using Cox regression. During the median follow-up time of 15 years, 7,008 men died from cancer. Men with prescription NSAID use had elevated cancer mortality (HR 2.02 95% CI 1.91-2.15 compared to non-users. The mortality risk was increased for lung, colorectal and pancreas cancer mortality (HR 2.68, 95%CI 2.40-2.99, HR 1.91, 95% CI 1.57-2.32 and HR 1.93, 95% CI 1.58-2.37, respectively. The increased risk remained in competing risks regression (HR 1.11, 95% CI 1.05-1.18. When the usage during the last three years of follow-up was excluded, the effect was reversed (HR 0.69, 95% CI 0.65-0.73. Cancer mortality was not decreased for prescription or over-the-counter aspirin use. However, in the competing risk regression analysis combined prescription and over-the-counter aspirin use was associated with decreased overall cancer mortality (HR 0.76, 95% CI 0.70-0.82. Cancer mortality was increased for NSAID users. However, the risk disappeared when the last 3 years were excluded.

Impact of time since diagnosis and mortality rate on cancer-associated venous thromboembolism - the Scandinavian Thrombosis and Cancer (STAC) cohort

DEFF Research Database (Denmark)

Blix, Kristine; Gran, Olga V; Severinsen, Marianne T

2018-01-01

BACKGROUND: Venous thromboembolism (VTE) is a common complication in cancer, and studies suggest that aggressive cancers harvest the highest risk of VTE. However, competing risk by death may result in over-estimation of VTE risk in cancers with high mortality. Therefore, we estimated the risk...... narrowed for all cancer sites after competing risk by death was taken into account (from 1-10% to 1-4%). CONCLUSION: The risk of VTE by cancer sites was influenced by the mortality rate and the time since cancer diagnosis. Our findings suggest that the cancer itself is a major contributor to VTE risk...... and that competing risk by death should be taken into account when exploring VTE risk in cancer. This article is protected by copyright. All rights reserved....

miR-106a suppresses tumor cells death in colorectal cancer through targeting ATG7.

Science.gov (United States)

Hao, Haibin; Xia, Guangfeng; Wang, Chao; Zhong, Fuping; Liu, Laipeng; Zhang, Dong

2017-06-01

Autophagy-related gene 7 (ATG7) and miR-106a play an important role in cancer cell autophagy and apoptosis, but the outcome of ATG7 and miR-106a in colorectal cancer (CRC) still remains not clear. In this study, we found that ATG7 and miR-106a expression were mutually related with cell death and prognosis in CRC patients. In addition, we also showed that ATG7 and miR-106a expression were changeable in colorectal cancer cell lines when compared with normal cell lines, but ATG7 and miR-106a mRNA level was negatively correlated. Furthermore, ATG7 protein and mRNA levels decreased after over-expression of miR-106a, whereas the suppression of ATG7 had the opposite effect. We confirmed that miR-106a down-regulated ATG7 mRNA level by binding the specific sequence of ATG7 mRNA 3'UTR region. Moreover, the over-expression of ATG7 induced CRC cells death both in vitro and in vivo. Taken together, our study data demonstrated that ATG7 aggravated the cell death of CRC, which was inhibited by miR-106a.

Patients with pancreatic cancer and relatives talk about preferred place of death and what influenced their preferences: a qualitative study.

Science.gov (United States)

Chapple, Alison; Evans, Julie; McPherson, Ann; Payne, Sheila

2011-12-01

To explore reasons why people with pancreatic cancer, who are reaching the end of their lives, say they wish to die at home or elsewhere, and why preferences may change. Qualitative study using semistructured interviews followed by thematic analysis. Respondents recruited from different parts of the UK during 2009/2010. 16 people with experience of pancreatic cancer (8 patients and 8 bereaved relatives) who discussed place of death in detail during an in-depth interview (from a total sample of 32 people with pancreatic cancer and eight relatives of others who had died of this disease). People's preferences were affected by their perceptions and previous experiences of care available at home, in a hospice or hospital. Preferences were also shaped by fears about possible loss of dignity, or fears of becoming a burden. Some people thought that a home death might leave bad memories for other members of the family. People with pancreatic cancer and their relatives were aware that preferences might change (or had changed) as death approached. The National Health Service End of Life Care Strategy for England seeks to meet the needs of people who are dying and promotes better support for home deaths. More information is needed about why patients hold different views about place of care and place of death, why patients' preferences change and what importance patients attach to place of death. Health professionals should bear this in mind if the subject is raised during advance care planning.

Nonpalpable breast cancer : mammographic and clinical findings

Energy Technology Data Exchange (ETDEWEB)

Seo, Jae Seung; Kim, Eun Kyung; Oh, Ki Keun; Cheon, Young Jik; Lee, Byung Chan [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

1998-08-01

To evaluate the mammographic and clinical findings of nonpalpable breast cancer. Materials and Methods : In 28 of 607 breast cancer patients examined between January 1994 and April 1997, lesions were nonpalpable. We retrospectively analyzed the mammographic, clinical and pathologic features of 25 patients (28 lesions) whose mammograms we obtained. Results : Among these 25 patients (28 lesions) screening was abnormal in 22; other symptoms were bloody nipple discharge(n=4), and nipple eczema(n=2). The patients were 34-62 (mean 52)years old. Invasive ductal carcinoma(n=13), DCIS(ductal carcinoma in situ, n-12), Paget's disease (n=2), and LCIS(lobular carcinoma in situ, n=1) were found during surgery. Six of 28 lesions(21%) showed evidence of axillary nodal metastasis;the majority arose from the upper outer quadrant of the breast (n=21). The mammographic findings were mass (50%), (and mass with microcalcification, 11%); microcalcification(29%); asymmetrical density(14%); and normal (7%). According to the mammographic density of breast parenchyma, the major finding in the low density group(N1+P1) was mass(9/9), and in the high density group(P2+DY) was microcalcification (12/19). Conclusion : The most common mammographic findings of nonpalpable breast cancer were mass (50%) and microcalcification(29%). Its features varied according to the mammographic density of breast parenchyma;mass was the main finding in the low density group and microcalcification in the high density group.

Nonpalpable breast cancer : mammographic and clinical findings

International Nuclear Information System (INIS)

Seo, Jae Seung; Kim, Eun Kyung; Oh, Ki Keun; Cheon, Young Jik; Lee, Byung Chan

1998-01-01

To evaluate the mammographic and clinical findings of nonpalpable breast cancer. Materials and Methods : In 28 of 607 breast cancer patients examined between January 1994 and April 1997, lesions were nonpalpable. We retrospectively analyzed the mammographic, clinical and pathologic features of 25 patients (28 lesions) whose mammograms we obtained. Results : Among these 25 patients (28 lesions) screening was abnormal in 22; other symptoms were bloody nipple discharge(n=4), and nipple eczema(n=2). The patients were 34-62 (mean 52)years old. Invasive ductal carcinoma(n=13), DCIS(ductal carcinoma in situ, n-12), Paget's disease (n=2), and LCIS(lobular carcinoma in situ, n=1) were found during surgery. Six of 28 lesions(21%) showed evidence of axillary nodal metastasis;the majority arose from the upper outer quadrant of the breast (n=21). The mammographic findings were mass (50%), (and mass with microcalcification, 11%); microcalcification(29%); asymmetrical density(14%); and normal (7%). According to the mammographic density of breast parenchyma, the major finding in the low density group(N1+P1) was mass(9/9), and in the high density group(P2+DY) was microcalcification (12/19). Conclusion : The most common mammographic findings of nonpalpable breast cancer were mass (50%) and microcalcification(29%). Its features varied according to the mammographic density of breast parenchyma;mass was the main finding in the low density group and microcalcification in the high density group

Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH) Is Pyruvylated during 3-Bromopyruvate Mediated Cancer Cell Death

Science.gov (United States)

Ganapathy-Kanniappan, Shanmugasundaram; Geschwind, Jean-Francois H.; Kunjithapatham, Rani; Buijs, Manon; Vossen, Josephina A.; Tchernyshyov, Irina; Cole, Robert N.; Syed, Labiq H.; Rao, Pramod P.; Ota, Shinichi; Vali, Mustafa

2013-01-01

Background The pyruvic acid analog 3-bromopyruvate (3BrPA) is an alkylating agent known to induce cancer cell death by blocking glycolysis. The anti-glycolytic effect of 3BrPA is considered to be the inactivation of glycolytic enzymes. Yet, there is a lack of experimental documentation on the direct interaction of 3BrPA with any of the suggested targets during its anticancer effect. Methods and Results In the current study, using radiolabeled (14C) 3BrPA in multiple cancer cell lines, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was identified as the primary intracellular target of 3BrPA, based on two-dimensional (2D) gel electrophoretic autoradiography, mass spectrometry and immunoprecipitation. Furthermore, in vitro enzyme kinetic studies established that 3BrPA has marked affinity to GAPDH. Finally, Annexin V staining and active caspase-3 immunoblotting demonstrated that apoptosis was induced by 3BrPA. Conclusion GAPDH pyruvylation by 3BrPA affects its enzymatic function and is the primary intracellular target in 3BrPA mediated cancer cell death. PMID:20044597

Validity and reliability of the persian version of templer death anxiety scale in family caregivers of cancer patients.

Science.gov (United States)

Soleimani, Mohammad Ali; Bahrami, Nasim; Yaghoobzadeh, Ameneh; Banihashemi, Hedieh; Nia, Hamid Sharif; Haghdoost, Ali Akbar

2016-01-01

Due to increasing recognition of the importance of death anxiety for understanding human nature, it is important that researchers who investigate death anxiety have reliable and valid methodology to measure. The purpose of this study was to evaluate the validity and reliability of the Persian version of Templer Death Anxiety Scale (TDAS) in family caregivers of cancer patients. A sample of 326 caregivers of cancer patients completed a 15-item questionnaire. Principal components analysis (PCA) followed by a varimax rotation was used to assess factor structure of the DAS. The construct validity of the scale was assessed using exploratory and confirmatory factor analyses. Convergent and discriminant validity were also examined. Reliability was assessed with Cronbach's alpha coefficients and construction reliability. Based on the results of the PCA and consideration of the meaning of our items, a three-factor solution, explaining 60.38% of the variance, was identified. A confirmatory factor analysis (CFA) then supported the adequacy of the three-domain structure of the DAS. Goodness-of-fit indices showed an acceptable fit overall with the full model {χ(2)(df) = 262.32 (61), χ(2)/df = 2.04 [adjusted goodness of fit index (AGFI) = 0.922, parsimonious comparative fit index (PCFI) = 0.703, normed fit Index (NFI) = 0.912, CMIN/DF = 2.048, root mean square error of approximation (RMSEA) = 0.055]}. Convergent and discriminant validity were shown with construct fulfilled. The Cronbach's alpha and construct reliability were greater than 0.70. The findings show that the Persian version of the TDAS has a three-factor structure and acceptable validity and reliability.

Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings

Science.gov (United States)

Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W.; Sisodiya, Sanjay M.

2015-01-01

Aims Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. Methods We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Results Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P epilepsy history and investigations. Conclusion Our findings support the contribution of examination of the whole fixed brain in SUDEP, with high rates of detection of relevant pathology. Availability of full clinical epilepsy‐related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. PMID:26300477

Nonthermal-plasma-mediated animal cell death

Science.gov (United States)

Kim, Wanil; Woo, Kyung-Chul; Kim, Gyoo-Cheon; Kim, Kyong-Tai

2011-01-01

Animal cell death comprising necrosis and apoptosis occurred in a well-regulated manner upon specific stimuli. The physiological meanings and detailed molecular mechanisms of cell death have been continuously investigated over several decades. Necrotic cell death has typical morphological changes, such as cell swelling and cell lysis followed by DNA degradation, whereas apoptosis shows blebbing formation and regular DNA fragmentation. Cell death is usually adopted to terminate cancer cells in vivo. The current strategies against tumour are based on the induction of cell death by adopting various methods, including radiotherapy and chemotherapeutics. Among these, radiotherapy is the most frequently used treatment method, but it still has obvious limitations. Recent studies have suggested that the use of nonthermal air plasma can be a prominent method for inducing cancer cell death. Plasma-irradiated cells showed the loss of genomic integrity, mitochondrial dysfunction, plasma membrane damage, etc. Tumour elimination with plasma irradiation is an emerging concept in cancer therapy and can be accelerated by targeting certain tumour-specific proteins with gold nanoparticles. Here, some recent developments are described so that the mechanisms related to plasma-mediated cell death and its perspectives in cancer treatment can be understood.

Nonthermal-plasma-mediated animal cell death

Energy Technology Data Exchange (ETDEWEB)

Kim, Wanil; Woo, Kyung-Chul; Kim, Kyong-Tai [Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja Dong, Pohang 790-784 (Korea, Republic of); Kim, Gyoo-Cheon, E-mail: ktk@postech.ac.kr [Department of Oral Anatomy and Cell Biology, School of Dentistry, Pusan National University, Yangsan 626-810 (Korea, Republic of)

2011-01-12

Animal cell death comprising necrosis and apoptosis occurred in a well-regulated manner upon specific stimuli. The physiological meanings and detailed molecular mechanisms of cell death have been continuously investigated over several decades. Necrotic cell death has typical morphological changes, such as cell swelling and cell lysis followed by DNA degradation, whereas apoptosis shows blebbing formation and regular DNA fragmentation. Cell death is usually adopted to terminate cancer cells in vivo. The current strategies against tumour are based on the induction of cell death by adopting various methods, including radiotherapy and chemotherapeutics. Among these, radiotherapy is the most frequently used treatment method, but it still has obvious limitations. Recent studies have suggested that the use of nonthermal air plasma can be a prominent method for inducing cancer cell death. Plasma-irradiated cells showed the loss of genomic integrity, mitochondrial dysfunction, plasma membrane damage, etc. Tumour elimination with plasma irradiation is an emerging concept in cancer therapy and can be accelerated by targeting certain tumour-specific proteins with gold nanoparticles. Here, some recent developments are described so that the mechanisms related to plasma-mediated cell death and its perspectives in cancer treatment can be understood. (topical review)

Nonthermal-plasma-mediated animal cell death

International Nuclear Information System (INIS)

Kim, Wanil; Woo, Kyung-Chul; Kim, Kyong-Tai; Kim, Gyoo-Cheon

2011-01-01

Animal cell death comprising necrosis and apoptosis occurred in a well-regulated manner upon specific stimuli. The physiological meanings and detailed molecular mechanisms of cell death have been continuously investigated over several decades. Necrotic cell death has typical morphological changes, such as cell swelling and cell lysis followed by DNA degradation, whereas apoptosis shows blebbing formation and regular DNA fragmentation. Cell death is usually adopted to terminate cancer cells in vivo. The current strategies against tumour are based on the induction of cell death by adopting various methods, including radiotherapy and chemotherapeutics. Among these, radiotherapy is the most frequently used treatment method, but it still has obvious limitations. Recent studies have suggested that the use of nonthermal air plasma can be a prominent method for inducing cancer cell death. Plasma-irradiated cells showed the loss of genomic integrity, mitochondrial dysfunction, plasma membrane damage, etc. Tumour elimination with plasma irradiation is an emerging concept in cancer therapy and can be accelerated by targeting certain tumour-specific proteins with gold nanoparticles. Here, some recent developments are described so that the mechanisms related to plasma-mediated cell death and its perspectives in cancer treatment can be understood. (topical review)

Non-apoptotic cell death associated with perturbations of macropinocytosis.

Science.gov (United States)

Maltese, William A; Overmeyer, Jean H

2015-01-01

Although macropinocytosis is widely recognized as a distinct form of fluid-phase endocytosis in antigen-presenting dendritic cells, it also occurs constitutively in many other normal and transformed cell types. Recent studies have established that various genetic or pharmacological manipulations can hyperstimulate macropinocytosis or disrupt normal macropinosome trafficking pathways, leading to accumulation of greatly enlarged cytoplasmic vacuoles. In some cases, this extreme vacuolization is associated with a unique form of non-apoptotic cell death termed "methuosis," from the Greek methuo (to drink to intoxication). It remains unclear whether cell death related to dysfunctional macropinocytosis occurs in normal physiological contexts. However, the finding that some types of cancer cells are particularly vulnerable to this unusual form of cell death has raised the possibility that small molecules capable of altering macropinosome trafficking or function might be useful as therapeutic agents against cancers that are resistant to drugs that work by inducing apoptosis. Herein we review examples of cell death associated with dysfunctional macropinocytosis and summarize what is known about the underlying mechanisms.

Non-apoptotic cell death associated with perturbations of macropinocytosis

Directory of Open Access Journals (Sweden)

William A. Maltese

2015-02-01

Full Text Available Although macropinocytosis is widely recognized as a distinct form of fluid-phase endocytosis in antigen-presenting dendritic cells, it also occurs constitutively in many other normal and transformed cell types. Recent studies have established that various genetic or pharmacological manipulations can hyperstimulate macropinocytosis or disrupt normal macropinosome trafficking pathways, leading to accumulation of greatly enlarged cytoplasmic vacuoles. In some cases, this extreme vacuolization is associated with a unique form of non-apoptotic cell death termed ‘methuosis’, from the Greek methuo (to drink to intoxication. It remains unclear whether cell death related to dysfunctional macropinocytosis occurs in normal physiological contexts. However, the finding that some types of cancer cells are particularly vulnerable to this unusual form of cell death has raised the possibility that small molecules capable of altering macropinosome trafficking or function might be useful as therapeutic agents against cancers that are resistant to drugs that work by inducing apoptosis. Herein we review examples of cell death associated with dysfunctional macropinocytosis and summarize what is known about the underlying mechanisms.

Cell death induced by taxanes in sensitive and resistant breast cancer cells

Czech Academy of Sciences Publication Activity Database

Ehrlichová, Marie; Truksa, Jaroslav; Naďová, Zuzana; Gut, I.; Kovář, Jan

2004-01-01

Roč. 37, č. 2 (2004), s. 120-121 ISSN 0960-7722. [Meeting of the European study group for cell proliferation /26./. Praha, 13.05.2004-16.05.2004] R&D Projects: GA MZd NL6715 Keywords : breast cancer cells * cell death * taxanes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.907, year: 2004

Oesophageal-cancer-derived death in the population of Belgrade in a period 1989-2006

Directory of Open Access Journals (Sweden)

Janković Janko

2009-01-01

Full Text Available Background/Aim. Oesophageal cancer is the sixth most common cause of death from all malignant tumors in the world (fifth in men, eighth in women. This cancer was estimated to account for about 529 000 new cases and about 442 000 deaths in the year 2007. In the year 2002 the highest standardized mortality rates (per 100 000 habitants of oesophageal carcinoma were noticed in the East Asia (men/women: 18.8/7.7 and East Africa (18.6/7.8, while the lowest were noticed in the Middle Africa (1.4/0.2 and West Africa (1.3/0.5. The aim of this descriptive epidemiologic study was to analyze epidemiologic situation of oesophageal cancer in Belgrade population during the period 1989-2006, using mortality data. Methods. Mortality data were collected from the City Organization for Statistics. In data analysis we used mortality rates which were standardized directly using those of the world population as the standard, and proportions. A denominator for mortality rates was calculated using the Belgrade population which was an average of the two latest register years (1991 and 2002. In order to analyze trend mortality from oesophageal cancer we used linear trend. Results. In Belgrade deaths from oesophageal cancer accounted for about 5.2% of all malignant tumors of intestinal system in male population, and 2.4% in female population. This cancer is, according to standardized mortality rates (per 100 000 habitants, on the fifth place in Belgrade population behind colorectal, stomach, pancreatic, liver and cholecystic cancer. During the period 1989-2006 in Belgrade 44 persons died from oesophageal carcinoma on the average each year, mainly men (75%, and the rest were women (25%. In male population during the same period we noticed a significant increase in trend mortality (y = 1.61 + 0.06x, p = 0.001, while in female population the increase of mortality was not significant. The male/female oesophageal cancer mortality ratio was 3:1. Mortality rates for oesophageal

(+)-Grandifloracin, an antiausterity agent, induces autophagic PANC-1 pancreatic cancer cell death.

Science.gov (United States)

Ueda, Jun-ya; Athikomkulchai, Sirivan; Miyatake, Ryuta; Saiki, Ikuo; Esumi, Hiroyasu; Awale, Suresh

2014-01-01

Human pancreatic tumors are known to be highly resistant to nutrient starvation, and this prolongs their survival in the hypovascular (austere) tumor microenvironment. Agents that retard this tolerance to nutrient starvation represent a novel antiausterity strategy in anticancer drug discovery. (+)-Grandifloracin (GF), isolated from Uvaria dac, has shown preferential toxicity to PANC-1 human pancreatic cancer cells under nutrient starvation, with a PC50 value of 14.5 μM. However, the underlying mechanism is not clear. In this study, GF was found to preferentially induce PANC-1 cell death in a nutrient-deprived medium via hyperactivation of autophagy, as evidenced by a dramatic upregulation of microtubule-associated protein 1 light chain 3. No change was observed in expression of the caspase-3 and Bcl-2 apoptosis marker proteins. GF was also found to strongly inhibit the activation of Akt, a key regulator of cancer cell survival and proliferation. Because pancreatic tumors are highly resistant to current therapies that induce apoptosis, the alternative cell death mechanism exhibited by GF provides a novel therapeutic insight into antiausterity drug candidates.

Does calcium in drinking water modify the association between nitrate in drinking water and risk of death from colon cancer?

Science.gov (United States)

Chiu, Hui-Fen; Tsai, Shang-Shyue; Chen, Pei-Shih; Wu, Trong-Neng; Yang, Chun-Yuh

2011-09-01

The objective of this study was to explore whether calcium (Ca) levels in drinking water modified the effects of nitrate on colon cancer risk. A matched case-control study was used to investigate the relationship between the risk of death from colon cancer and exposure to nitrate in drinking water in Taiwan. All colon cancer deaths of Taiwan residents from 2003 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth and year of death. Information on the levels of nitrate-nitrogen (NO(3)-N) and Ca in drinking water have been collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cases and controls was assumed to be the source of the subject's NO(3)-N and Ca exposure via drinking water. We observed evidence of an interaction between drinking water NO(3)-N and Ca intake via drinking water. This is the first study to report effect modification by Ca intake from drinking water on the association between NO(3)-N exposure and risk of colon cancer mortality.

Non-chemotoxic induction of cancer cell death using magnetic nanowires

Directory of Open Access Journals (Sweden)

Contreras MF

2015-03-01

Full Text Available Maria F Contreras,1 Rachid Sougrat,2 Amir Zaher,3 Timothy Ravasi,1,3 Jürgen Kosel3 1Division of Biological and Environmental Sciences and Engineering, 2Advanced Nanofabrication Imaging and Characterization, 3Division of Computer, Electrical and Mathematical Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia Abstract: In this paper, we show that magnetic nanowires with weak magnetic fields and low frequencies can induce cell death via a mechanism that does not involve heat production. We incubated colon cancer cells with two concentrations (2.4 and 12 µg/mL of nickel nanowires that were 35 nm in diameter and exposed the cells and nanowires to an alternating magnetic field (0.5 mT and 1 Hz or 1 kHz for 10 or 30 minutes. This low-power field exerted a force on the magnetic nanowires, causing a mechanical disturbance to the cells. Transmission electron microscopy images showed that the nanostructures were internalized into the cells within 1 hour of incubation. Cell viability studies showed that the magnetic field and the nanowires separately had minor deleterious effects on the cells; however, when combined, the magnetic field and nanowires caused the cell viability values to drop by up to 39%, depending on the strength of the magnetic field and the concentration of the nanowires. Cell membrane leakage experiments indicated membrane leakage of 20%, suggesting that cell death mechanisms induced by the nanowires and magnetic field involve some cell membrane rupture. Results suggest that magnetic nanowires can kill cancer cells. The proposed process requires simple and low-cost equipment with exposure to only very weak magnetic fields for short time periods. Keywords: cell death induction, low frequency alternating magnetic field, nanomedicine, nanowire internalization, nickel nanowires

Non-chemotoxic induction of cancer cell death using magnetic nanowires

KAUST Repository

Contreras, Maria F.; Sougrat, Rachid; Zaher, Amir Omar; Ravasi, Timothy; Kosel, Jü rgen

2015-01-01

In this paper, we show that magnetic nanowires with weak magnetic fields and low frequencies can induce cell death via a mechanism that does not involve heat production. We incubated colon cancer cells with two concentrations (2.4 and 12 μg/mL) of nickel nanowires that were 35 nm in diameter and exposed the cells and nanowires to an alternating magnetic field (0.5 mT and 1 Hz or 1 kHz) for 10 or 30 minutes. This low-power field exerted a force on the magnetic nanowires, causing a mechanical disturbance to the cells. Transmission electron microscopy images showed that the nanostructures were internalized into the cells within 1 hour of incubation. Cell viability studies showed that the magnetic field and the nanowires separately had minor deleterious effects on the cells; however, when combined, the magnetic field and nanowires caused the cell viability values to drop by up to 39%, depending on the strength of the magnetic field and the concentration of the nanowires. Cell membrane leakage experiments indicated membrane leakage of 20%, suggesting that cell death mechanisms induced by the nanowires and magnetic field involve some cell membrane rupture. Results suggest that magnetic nanowires can kill cancer cells. The proposed process requires simple and low-cost equipment with exposure to only very weak magnetic fields for short time periods. © 2015 Contreras et al.

Non-chemotoxic induction of cancer cell death using magnetic nanowires

KAUST Repository

Contreras, Maria F.

2015-03-01

In this paper, we show that magnetic nanowires with weak magnetic fields and low frequencies can induce cell death via a mechanism that does not involve heat production. We incubated colon cancer cells with two concentrations (2.4 and 12 μg/mL) of nickel nanowires that were 35 nm in diameter and exposed the cells and nanowires to an alternating magnetic field (0.5 mT and 1 Hz or 1 kHz) for 10 or 30 minutes. This low-power field exerted a force on the magnetic nanowires, causing a mechanical disturbance to the cells. Transmission electron microscopy images showed that the nanostructures were internalized into the cells within 1 hour of incubation. Cell viability studies showed that the magnetic field and the nanowires separately had minor deleterious effects on the cells; however, when combined, the magnetic field and nanowires caused the cell viability values to drop by up to 39%, depending on the strength of the magnetic field and the concentration of the nanowires. Cell membrane leakage experiments indicated membrane leakage of 20%, suggesting that cell death mechanisms induced by the nanowires and magnetic field involve some cell membrane rupture. Results suggest that magnetic nanowires can kill cancer cells. The proposed process requires simple and low-cost equipment with exposure to only very weak magnetic fields for short time periods. © 2015 Contreras et al.

Dietary habits and risk of urothelial cancer death in a large-scale cohort study (JACC Study) in Japan.

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Sakauchi, Fumio; Mori, Mitsuru; Washio, Masakazu; Watanabe, Yoshiyuki; Ozasa, Kotaro; Hayashi, Kyohei; Miki, Tsuneharu; Nakao, Masahiro; Mikami, Kazuya; Ito, Yoshinori; Wakai, Kenji; Tamakoshi, Akiko

2004-01-01

In the present study, the associations of dietary habits with the risk of urothelial cancer death were evaluated taking into consideration sex, age, and smoking habits. The Japan Collaborative Cohort Study was established in 1988-1990 and consisted of 47,997 men and 66,520 women observed until the end of 1999. A self-administered food-frequency questionnaire was used as a baseline survey. Hazard ratios for dietary factors were calculated by Cox's proportional hazards model. During the observation period, 63 men and 25 women died of urothelial cancer. Increasing age, male gender, and history of smoking were all significantly associated with increased risk of urothelial cancer death. A high intake of milk and fruits other than oranges reduced the risk significantly and dose dependently, in particular among subjects with smoking history. However, consumption of butter and yogurt had no associations with the risk. Intakes of cabbage, lettuce, green leafy vegetables, carrots, squash, tomatoes, and oranges were not significantly associated with the risk. It was suggested that urothelial cancer death could be potentially preventable by smoking cessation and regular intake of milk and fruit.

Symptom prevalence, intensity, and distress in patients with inoperable lung cancer in relation to time of death

NARCIS (Netherlands)

Tishelman, Carol; Petersson, Lena-Marie; Degner, Lesley F.; Sprangers, Mirjam A. G.

2007-01-01

Purpose To examine symptom prevalence, intensity, and association with distress in patients with inoperable lung cancer (LC), using time to death as point of reference. Patients and Methods A consecutive sample of 400 patients completed the European Organisation for Research and Treatment of Cancer

Pathophysiological mechanisms of death resistance in colorectal carcinoma.

Science.gov (United States)

Huang, Ching-Ying; Yu, Linda Chia-Hui

2015-11-07

Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors.

Perspectives on death and an afterlife in relation to quality of life, depression, and hopelessness in cancer patients without evidence of disease and advanced cancer patients

NARCIS (Netherlands)

Laarhoven, H.W.M. van; Schilderman, J.; Verhagen, C.A.H.H.V.M.; Vissers, K.C.P.; Prins, J.B.

2011-01-01

CONTEXT: It is unknown whether cancer patients with different life expectancies have different attitudes and emotions toward death and an afterlife. Also, it is unclear whether these attitudes and emotions toward death and afterlife influence patients' distress. OBJECTIVES: To assess the

Effectiveness of screening colonoscopy in reducing the risk of death from right and left colon cancer: a large community-based study.

Science.gov (United States)

Doubeni, Chyke A; Corley, Douglas A; Quinn, Virginia P; Jensen, Christopher D; Zauber, Ann G; Goodman, Michael; Johnson, Jill R; Mehta, Shivan J; Becerra, Tracy A; Zhao, Wei K; Schottinger, Joanne; Doria-Rose, V Paul; Levin, Theodore R; Weiss, Noel S; Fletcher, Robert H

2018-02-01

Screening colonoscopy's effectiveness in reducing colorectal cancer mortality risk in community populations is unclear, particularly for right-colon cancers, leading to recommendations against its use for screening in some countries. This study aimed to determine whether, among average-risk people, receipt of screening colonoscopy reduces the risk of dying from both right-colon and left-colon/rectal cancers. We conducted a nested case-control study with incidence-density matching in screening-eligible Kaiser Permanente members. Patients who were 55-90 years old on their colorectal cancer death date during 2006-2012 were matched on diagnosis (reference) date to controls on age, sex, health plan enrolment duration and geographical region. We excluded patients at increased colorectal cancer risk, or with prior colorectal cancer diagnosis or colectomy. The association between screening colonoscopy receipt in the 10-year period before the reference date and colorectal cancer death risk was evaluated while accounting for other screening exposures. We analysed 1747 patients who died from colorectal cancer and 3460 colorectal cancer-free controls. Compared with no endoscopic screening, receipt of a screening colonoscopy was associated with a 67% reduction in the risk of death from any colorectal cancer (adjusted OR (aOR)=0.33, 95% CI 0.21 to 0.52). By cancer location, screening colonoscopy was associated with a 65% reduction in risk of death for right-colon cancers (aOR=0.35, CI 0.18 to 0.65) and a 75% reduction for left-colon/rectal cancers (aOR=0.25, CI 0.12 to 0.53). Screening colonoscopy was associated with a substantial and comparably decreased mortality risk for both right-sided and left-sided cancers within a large community-based population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings

Science.gov (United States)

Pane, Masdalina; Imari, Sholah; Alwi, Qomariah; Nyoman Kandun, I; Cook, Alex R.; Samaan, Gina

2013-01-01

Background Indonesia provides the largest single source of pilgrims for the Hajj (10%). In the last two decades, mortality rates for Indonesian pilgrims ranged between 200–380 deaths per 100,000 pilgrims over the 10-week Hajj period. Reasons for high mortality are not well understood. In 2008, verbal autopsy was introduced to complement routine death certificates to explore cause of death diagnoses. This study presents the patterns and causes of death for Indonesian pilgrims, and compares routine death certificates to verbal autopsy findings. Methods Public health surveillance was conducted by Indonesian public health authorities accompanying pilgrims to Saudi Arabia, with daily reporting of hospitalizations and deaths. Surveillance data from 2008 were analyzed for timing, geographic location and site of death. Percentages for each cause of death category from death certificates were compared to that from verbal autopsy. Results In 2008, 206,831 Indonesian undertook the Hajj. There were 446 deaths, equivalent to 1,968 deaths per 100,000 pilgrim years. Most pilgrims died in Mecca (68%) and Medinah (24%). There was no statistically discernible difference in the total mortality risk for the two pilgrimage routes (Mecca or Medinah first), but the number of deaths peaked earlier for those traveling to Mecca first (p=0.002). Most deaths were due to cardiovascular (66%) and respiratory (28%) diseases. A greater proportion of deaths were attributed to cardiovascular disease by death certificate compared to the verbal autopsy method (pIndonesian pilgrim mortality rates were very high. Correct classification of cause of death is critical for the development of risk mitigation strategies. Since verbal autopsy classified causes of death differently to death certificates, further studies are needed to assess the method’s utility in this setting. PMID:23991182

Good death in elderly adults with cancer in Japan based on perspectives of the general population.

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Akechi, Tatsuo; Miyashita, Mitsunori; Morita, Tatsuya; Okuyama, Toru; Sakamoto, Masaki; Sagawa, Ryuichi; Uchitomi, Yosuke

2012-02-01

To investigate concepts relevant to a good death in elderly adults with cancer. Cross-sectional. Japan. A national sample of 2,595 adults, including 466 aged 70 to 79. An anonymous questionnaire covering 18 domains (physical and psychological comfort, dying in a favorite place, good relationship with medical staff, maintaining hope and pleasure, not being a burden to others, good relationship with family, physical and cognitive control, environmental comfort, being respected as an individual, life completion, natural death, preparation for death, role accomplishment and contribution to others, unawareness of death, fighting against cancer, pride and beauty, control over the future, and religious and spiritual comfort) and two additional concepts (pokkuri (sudden death) and omakase (leaving the decisions to a medical expert) was completed. The difference in importance of the concept between two age groups (40-69 and 70-79) was investigated using effect sizes (ESs). Clinically significant differences in the concept of good death were observed for two domains and one component: not being a burden to others (ES = -0.24), role accomplishment and contribution to others (ES = 0.29), and omakase (leaving the decisions to a medical expert; ES = 0.60). Only a few differences in the concept of good death existed between elderly and younger adults. When caring for terminally ill elderly Japanese adults, medical staff should acknowledge that some elderly adults value the traditional paternalistic attitude of physicians and that not all people want to be actively involved in decision-making. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

miR-203 inhibits cell proliferation and promotes cisplatin induced cell death in tongue squamous cancer

Energy Technology Data Exchange (ETDEWEB)

Lin, Jiong; Lin, Yao [Guangdong Provincial Key Laboratory of Stomatology, Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510055 (China); Fan, Li [Department of Pharmaceutical Analysis, School of Pharmacy, The Fourth Military Medical University, Xi' an, Shaanxi, 710032 (China); Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055 (China); Kuang, Wei [Department of Stomatology, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou, 510010 (China); Zheng, Liwei [State Key Laboratory of Oral Diseases, Sichuan University, Wuhou District, Chengdu, 610041 (China); Wu, Jiahua [Guangdong Provincial Key Laboratory of Stomatology, Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510055 (China); Shang, Peng [Patient-specific Orthopedic Technology Research Center in GuangDong Research Centre for Neural Engineering, 1068 Xueyuan Boulevard, University Town of Shenzhen, Xili, Nanshan, Shenzhen, 518055 (China); Wang, Qiaofeng [Department of Pharmaceutical Chemistry, School of Pharmacy, The Fourth Military Medical University, Xi' an, Shanxi, 710032 (China); Tan, Jiali, E-mail: jasminenov@163.com [Guangdong Provincial Key Laboratory of Stomatology, Department of Orthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, 510055 (China)

2016-04-29

Oral squamous cell carcinoma (OSCC) is one of the most common types of the head and neck cancer. Chemo resistance of OSCC has been identified as a substantial therapeutic hurdle. In this study, we analyzed the role of miR-203 in the OSCC and its effects on cisplatin-induced cell death in an OSCC cell line, Tca8113. There was a significant decrease of miR-203 expression in OSCC samples, compared with the adjacent normal, non-cancerous tissue. After 3 days cisplatin treatment, the survived Tca8113 cells had a lower expression of miR-203 than that in the untreated control group. In contrast, PIK3CA showed an inverse expression in cancer and cisplatin survived Tca8113 cells. Transfection of Tca8113 cells with miR-203 mimics greatly reduced PIK3CA expression and Akt activation. Furthermore, miR-203 repressed PIK3CA expression through targeting the 3′UTR. Restoration of miR-203 not only suppressed cell proliferation, but also sensitized cells to cisplatin induced cell apoptosis. This effect was absent in cells that were simultaneously treated with PIK3CA RNAi. In summary, these findings suggest miR-203 plays an important role in cisplatin resistance in OSCC, and furthermore delivery of miR-203 analogs may serve as an adjuvant therapy for OSCC. - Highlights: • Much lower miR-203 expression in cisplatin resistant Tca8113 cells is discovered. • Delivery of miR-203 can sensitize the Tca8113 cells to cisplatin induced cell death. • MiR-203 can downregulate PIK3CA through the 3′UTR. • The effects of miR-203 on cisplatin sensitivity is mainly through PIK3CA pathway.

Preferred place of care and place of death of the general public and cancer patients in Japan.

Science.gov (United States)

Yamagishi, Akemi; Morita, Tatsuya; Miyashita, Mitsunori; Yoshida, Saran; Akizuki, Nobuya; Shirahige, Yutaka; Akiyama, Miki; Eguchi, Kenji

2012-10-01

Dying at a favorite place is one of the important determinants for terminally ill cancer patients. The primary aim was to clarify (1) differences in preferred place of care and place of death among the general public across four areas across Japan and (2) preferred place of care and place of death among community-representative cancer patients. A cross-sectional mail survey was conducted on 8,000 randomly selected general population. We examined preferred place of care and place of death using two vignettes and obtained a total of 3,984 (50%) responses. For the pain scenario, approximately 50% of the general public throughout four areas chose home as their preferred place of care; and for the dependent-without-pain scenario, about 40% chose home as preferred place of care. In cancer patients, for both scenarios, approximately 40% chose home as the preferred place of care, and they were significantly less likely to choose home. The most preferred combination of place of care and place of death was home hospice for both groups. Although there were statistically significant differences in preferred place of care and place of death among the four regions, the absolute difference was less than 8%. Independent determinants of choosing home as place of care included concern about family burden and being unable to adequately respond to sudden changes out of working hours. In conclusion, establishing more accessible home and hospice service is strongly required through arranging regional resources to reduce family burden, alleviating patient-perceived burdens, and improving 24-h support at home.

Perspectives on death and an afterlife in relation to quality of life, depression, and hopelessness in cancer patients without evidence of disease and advanced cancer patients

NARCIS (Netherlands)

van Laarhoven, Hanneke W. M.; Schilderman, Johannes; Verhagen, Constans A. H. H. V. M.; Vissers, Kris C.; Prins, Judith

2011-01-01

It is unknown whether cancer patients with different life expectancies have different attitudes and emotions toward death and an afterlife. Also, it is unclear whether these attitudes and emotions toward death and afterlife influence patients' distress. To assess the relationship of attitudes and

Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells.

Science.gov (United States)

Lin, Chiou-Feng; Chen, Chia-Ling; Chien, Shun-Yi; Tseng, Po-Chun; Wang, Yu-Chih; Tsai, Tsung-Ting

2016-01-01

We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression. STAT1-mediated IFN regulatory factor-1 activation was essential for upregulating ROS production. By genetically silencing p47phox, IFN-γ-induced ROS and mimic ETosis were significantly attenuated. This mechanistic study indicated that ROS may mediate DNA damage followed by histone H3 citrullination. Furthermore, ROS promoted IFN-γ-induced mimic ETosis in cooperation with autophagy. These findings further demonstrate that ROS regulates IFN-γ-induced mimic ETosis in lung epithelial malignancy.

Fluvastatin mediated breast cancer cell death: a proteomic approach to identify differentially regulated proteins in MDA-MB-231 cells.

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Anantha Koteswararao Kanugula

Full Text Available Statins are increasingly being recognized as anti-cancer agents against various cancers including breast cancer. To understand the molecular pathways targeted by fluvastatin and its differential sensitivity against metastatic breast cancer cells, we analyzed protein alterations in MDA-MB-231 cells treated with fluvastatin using 2-DE in combination with LC-MS/MS. Results revealed dys-regulation of 39 protein spots corresponding to 35 different proteins. To determine the relevance of altered protein profiles with breast cancer cell death, we mapped these proteins to major pathways involved in the regulation of cell-to-cell signaling and interaction, cell cycle, Rho GDI and proteasomal pathways using IPA analysis. Highly interconnected sub networks showed that vimentin and ERK1/2 proteins play a central role in controlling the expression of altered proteins. Fluvastatin treatment caused proteolysis of vimentin, a marker of epithelial to mesenchymal transition. This effect of fluvastatin was reversed in the presence of mevalonate, a downstream product of HMG-CoA and caspase-3 inhibitor. Interestingly, fluvastatin neither caused an appreciable cell death nor did modulate vimentin expression in normal mammary epithelial cells. In conclusion, fluvastatin alters levels of cytoskeletal proteins, primarily targeting vimentin through increased caspase-3- mediated proteolysis, thereby suggesting a role for vimentin in statin-induced breast cancer cell death.

Disability Rating, Age at Death, and Cause of Death in U.S. Veterans with Service-Connected Conditions.

Science.gov (United States)

Maynard, Charles; Trivedi, Ranak; Nelson, Karin; Fihn, Stephan D

2018-03-26

cancer or cardiovascular conditions and <2% were due to external causes. In the youngest group, cardiovascular disease and cancer accounted for about 1/3 of deaths, whereas external causes or deaths due to accidents, suicide, or assault accounted for nearly 33% of deaths. For Veterans with service-connected PTSD or major depression; 6.5% of deaths were due to external causes whereas for Veterans without these conditions, only 3.1% were due to external causes. The finding of premature death due to external causes in the youngest age group as well as the finding of higher proportions of external causes in those with PTSD or major depression should be of great concern to those who care for Veterans.

Does exclusion of cancers registered only from death-certificate information diminish socio-demographic disparities in recorded survival?

Science.gov (United States)

Tervonen, Hanna E; Roder, David; Morrell, Stephen; You, Hui; Currow, David C

2017-06-01

Death Certificate Only (DCO) cancer cases are commonly excluded from survival analyses due to unknown survival time. This study examines whether socio-demographic factors are associated with DCO diagnosis, and the potential effects of excluding DCO cases on socio-demographic cancer survival disparities in NSW, Australia. NSW Cancer Registry data for cases diagnosed in 2000-2008 were used in this study. Logistic regression was used to estimate the odds of DCO registration by socio-demographic sub-group (socio-economic disadvantage, residential remoteness, country of birth, age at diagnosis). Cox proportional hazard regression was used to estimate the probability of death from cancer by socio-demographic subgroup when DCO cases were included and excluded from analyses. DCO cases consisted of 1.5% (n=4336) of all cases (n=299,651). DCO diagnosis was associated with living in socio-economically disadvantaged areas (most disadvantaged compared with least disadvantaged quintile: odds ratio OR 1.25, 95%CI 1.12-1.40), living in inner regional (OR 1.16, 95%CI 1.08-1.25) or remote areas (OR 1.48, 95%CI 1.01-2.19), having an unknown country of birth (OR 1.63, 95%CI 1.47-1.81) and older age. Including or excluding DCO cases had no significant impact on hazard ratios for cancer death by socio-economic disadvantage quintile or remoteness category, and only a minor impact on hazard ratios by age. Socio-demographic factors were associated with DCO diagnosis in NSW. However, socio-demographic cancer survival disparities remained unchanged or varied only slightly irrespective of including/excluding DCO cases. Further research could examine the upper limits of DCO proportions that significantly alter estimated cancer survival differentials if DCOs are excluded. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Analysis of over 10,000 Cases finds no association between previously reported candidate polymorphisms and ovarian cancer outcome

DEFF Research Database (Denmark)

White, Kristin L; Vierkant, Robert A; Fogarty, Zachary C

2013-01-01

Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis...

Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death

Energy Technology Data Exchange (ETDEWEB)

Sun, Hengwen [Department of Radiation, Cancer Center of Guangdong General Hospital (Guangdong Academy of Medical Science), Guangzhou, 510080, Guangdong (China); Yang, Shana; Li, Jianhua [Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China); Zhang, Yajie [Department of Pathology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China); Gao, Dongsheng [Department of Oncology, Guangdong Medical College Affiliated Pengpai Memorial Hospital, Hai Feng, 516400, Gungdong (China); Zhao, Shenting, E-mail: zhaoshenting@126.com [Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, Guangdong (China)

2016-03-25

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy. - Highlights: • AIF nuclear translocation is involved in ionizing radiation induced hepatocellular carcinoma cell line HepG2 cell death. • AIF mediated cell death induced by ionizing radiation is caspase-independent. • Caspase-independent pathway is involved in ionzing radiation induced HepG2 cell death.

Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death

International Nuclear Information System (INIS)

Sun, Hengwen; Yang, Shana; Li, Jianhua; Zhang, Yajie; Gao, Dongsheng; Zhao, Shenting

2016-01-01

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy. - Highlights: • AIF nuclear translocation is involved in ionizing radiation induced hepatocellular carcinoma cell line HepG2 cell death. • AIF mediated cell death induced by ionizing radiation is caspase-independent. • Caspase-independent pathway is involved in ionzing radiation induced HepG2 cell death.

Skin Cancer (Including Melanoma)—Patient Version

Science.gov (United States)

Skin cancer is the most common type of cancer. The main types of skin cancer are squamous cell carcinoma, basal cell carcinoma, and melanoma. Most deaths from skin cancer are caused by melanoma. Start here to find information on skin cancer treatment, causes and prevention, screening, research, and statistics.

Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis.

Science.gov (United States)

Storm, P; Aits, S; Puthia, M K; Urbano, A; Northen, T; Powers, S; Bowen, B; Chao, Y; Reindl, W; Lee, D Y; Sullivan, N L; Zhang, J; Trulsson, M; Yang, H; Watson, J D; Svanborg, C

2011-12-01

HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here, we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small-hairpin RNA (shRNA) inhibition, proteomic and metabolomic technology, we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, HAMLET sensitivity was modified by the glycolytic state of tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen, hexokinase 1 (HK1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 and hypoxia-inducible factor 1α modified HAMLET sensitivity. HK1 was shown to bind HAMLET in a protein array containing ∼8000 targets, and HK activity decreased within 15 min of HAMLET treatment, before morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 min. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene addiction or the Warburg effect.

Conserved features of cancer cells define their sensitivity of HAMLET-induced death; c-Myc and glycolysis

Science.gov (United States)

Storm, Petter; Puthia, Manoj Kumar; Aits, Sonja; Urbano, Alexander; Northen, Trent; Powers, Scott; Bowen, Ben; Chao, Yinxia; Reindl, Wolfgang; Lee, Do Yup; Sullivan, Nancy Liu; Zhang, Jianping; Trulsson, Maria; Yang, Henry; Watson, James; Svanborg, Catharina

2014-01-01

HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small hairpin RNA inhibition, proteomic and metabolomic technology we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted the sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, the HAMLET sensitivity was modified by the glycolytic state of the tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen Hexokinase 1, PFKFB1 and HIF1α modified HAMLET sensitivity. Hexokinase 1 was shown to bind HAMLET in a protein array containing approximately 8000 targets and Hexokinase activity decreased within 15 minutes of HAMLET treatment, prior to morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. The glycolytic machinery was modified and glycolysis was shifted towards the pentose phosphate pathway. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 minutes. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene-addiction or the Warburg effect. PMID:21643007

Associations of Coffee Drinking and Cancer Mortality in the Cancer Prevention Study-II.

Science.gov (United States)

Gapstur, Susan M; Anderson, Rebecca L; Campbell, Peter T; Jacobs, Eric J; Hartman, Terryl J; Hildebrand, Janet S; Wang, Ying; McCullough, Marjorie L

2017-10-01

Background: Associations of coffee consumption with cancer mortality are inconsistent for many types of cancer, and confounding by smoking is an important concern. Methods: Cox proportional hazards regression was used to estimate multivariable-adjusted HRs for coffee consumption associated with death from all cancers combined and from specific cancer types among 922,896 Cancer Prevention Study-II participants ages 28-94 years who completed a four-page questionnaire and were cancer free at baseline in 1982. Results: During follow-up through 2012, there were 118,738 cancer-related deaths. There was a nonlinear association between coffee consumption and all-cancer death among current smokers and former smokers and no association among never smokers. Among nonsmokers, a 2 cup/day increase in coffee consumption was inversely associated with death from colorectal [HR = 0.97; 95% confidence interval (CI) 0.95-0.99], liver [HR = 0.92; 95% CI, 0.88-0.96], and female breast (HR = 0.97; 95% CI, 0.94-0.99) cancers, and positively associated with esophageal cancer-related death (HR = 1.07; 95% CI, 1.02-1.12). For head and neck cancer, a nonlinear inverse association was observed starting at 2-3 cups per day (HR = 0.72; 95% CI, 0.55-0.95), with similar associations observed at higher levels of consumption. Conclusions: These findings are consistent with many other studies that suggest coffee drinking is associated with a lower risk of colorectal, liver, female breast, and head and neck cancer. The association of coffee consumption with higher risk of esophageal cancer among nonsmokers in our study should be confirmed. Impact: These results underscore the importance of assessing associations between coffee consumption and cancer mortality by smoking status. Cancer Epidemiol Biomarkers Prev; 26(10); 1477-86. ©2017 AACR . ©2017 American Association for Cancer Research.

Quantitative evaluation of the lung cancer deaths attributable to residential radon: A simple method and results for all the 21 Italian Regions

International Nuclear Information System (INIS)

Bochicchio, F.; Antignani, S.; Venoso, G.; Forastiere, F.

2013-01-01

Pooled analyses of epidemiological case-control studies on lung cancer and residential radon have shown that radon exposure in dwellings increases lung cancer risk, and that the increase is statistically significant also for prolonged exposures to low-medium level of radon concentration, i.e. levels commonly found in many dwellings. In this paper, a simple method to evaluate the health burden due to the presence of radon in homes (i.e. the number of lung cancer deaths attributable to radon exposure in dwellings) was presented. This method is based on the following parameters: i) the excess relative risk per unit of exposure evaluated in case-control studies; ii) the average radon concentration that can be considered representative of population exposure in dwellings; iii) the total number of lung cancer deaths occurring each year. Moreover, the interaction between radon and cigarette smoking is needed to be taken into account: in fact, although most of the persons are non-smokers, most of the lung cancer deaths attributed to radon are actually due to the multiplicative effect of radon and cigarette smoking. To show this effect, the number of radon related lung cancer deaths estimated to occur among current, former and never smokers was calculated separately for males and females, taking into account the relative risk of lung cancer for the different smoking categories and the prevalence of smoking habits. The methodology described in this work was applied to all the 21 Italian Regions in order to illustrate it. The overall fraction of lung cancer deaths attributable to radon in Italy is about 10%, with values in individual Regions ranging from 4% to 16%. The greater part of the lung cancers attributable to radon is estimated to occur among current smokers for both males and females (72% and 60%, respectively, at national level). This is due to the synergistic effects of radon and cigarette smoking, which should therefore be taken into account in policies aimed to

Roentgenological findings in the non-cancerous portion of the stomach with early gastric cancer

Energy Technology Data Exchange (ETDEWEB)

Komatsu, Yukihisa

1987-10-01

Roentgenological findings of the fine reliefs in the non-cancerous portion were studied in 61 patients with early gastric cancer by double contrast examination. Incidence of the various types of the fine reliefs in the non-cancerous portion were as follows;verrucae 4 %, granularity 34 %, fine granularity 58 %, islet 24 %, network 17 % and irregular network 16 %, respectively. Fine granularity and network were observed in 61 % and 46 % of the cases with poorly differentiated adenocarcinoma, respectively. Granularity, fine granularity and irregular network were observed in 30 %, 55 % and 40 % of the cases with signet-ring cell carcinoma, respectively. Granularity, fine granularity and islet were observed in 41 %, 59 % and 30 % of the cases with tubular adenocarcinoma, respectively. These results suggest that fine reliefs in the non-cancerous portion of the stomach with early gastric cancer showed both findings those found in atrophic gastritis (verrucae, granularity, fine granularity and network) and those in gastric cancer (granularity, fine granularity, islet and irregular network).

Roentgenological findings in the non-cancerous portion of the stomach with early gastric cancer

International Nuclear Information System (INIS)

Komatsu, Yukihisa

1987-01-01

Roentgenological findings of the fine reliefs in the non-cancerous portion were studied in 61 patients with early gastric cancer by double contrast examination. Incidence of the various types of the fine reliefs in the non-cancerous portion were as follows ; verrucae 4 %, granularity 34 %, fine granularity 58 %, islet 24 %, network 17 % and irregular network 16 %, respectively. Fine granularity and network were observed in 61 % and 46 % of the cases with poorly differentiated adenocarcinoma, respectively. Granularity, fine granularity and irregular network were observed in 30 %, 55 % and 40 % of the cases with signet-ring cell carcinoma, respectively. Granularity, fine granularity and islet were observed in 41 %, 59 % and 30 % of the cases with tubular adenocarcinoma, respectively. These results suggest that fine reliefs in the non-cancerous portion of the stomach with early gastric cancer showed both findings those found in atrophic gastritis (verrucae, granularity, fine granularity and network) and those in gastric cancer (granularity, fine granularity, islet and irregular network). (author)

Certified causes of death in patients with mesothelioma in South East England

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Peto Julian

2009-01-01

Full Text Available Abstract Background Mesothelioma is a highly fatal cancer that is caused by exposure to asbestos fibres. In many populations, the occurrence of mesothelioma is monitored with the use of mortality data from death certification. We examine certified causes of death of patients who have been diagnosed with mesothelioma, and assess the validity of death certification data as a proxy for mesothelioma incidence. Methods We extracted mesothelioma registrations in the South East of England area between 2000 and 2004 from the Thames Cancer Registry database. We retained for analysis 2200 patients who had died at the time of analysis, after having excluded seven dead cases where the causes of death were not known to the cancer registry. The 2200 deaths were classified hierarchically to identify (1 mesothelioma deaths, (2 deaths certified as lung cancer deaths or (3 deaths from unspecified cancer, and (4 deaths from other causes. Results 87% of the patients had mesothelioma mentioned on the death certificate. 6% had no mention of mesothelioma but included lung cancer as a cause of death. Another 6% had no mention of mesothelioma or lung cancer, but included an unspecified cancer as a cause of death. Lastly, 2% had other causes of death specified on the death certificate. Conclusion This analysis suggests that official mortality data may underestimate the true occurrence of mesothelioma by around 10%.

The Application of Non-Invasive Apoptosis Detection Sensor (NIADS on Histone Deacetylation Inhibitor (HDACi-Induced Breast Cancer Cell Death

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Kai-Wen Hsu

2018-02-01

Full Text Available Breast cancer is the most common malignancy in women and the second leading cause of cancer death in women. Triple negative breast cancer (TNBC subtype is a breast cancer subset without ER (estrogen receptor, PR (progesterone receptor and HER2 (human epidermal growth factor receptor 2 expression, limiting treatment options and presenting a poorer survival rate. Thus, we investigated whether histone deacetylation inhibitor (HDACi could be used as potential anti-cancer therapy on breast cancer cells. In this study, we found TNBC and HER2-enriched breast cancers are extremely sensitive to Panobinostat, Belinostat of HDACi via experiments of cell viability assay, apoptotic marker identification and flow cytometry measurement. On the other hand, we developed a bioluminescence-based live cell non-invasive apoptosis detection sensor (NIADS detection system to evaluate the quantitative and kinetic analyses of apoptotic cell death by HDAC treatment on breast cancer cells. In addition, the use of HDACi may also contribute a synergic anti-cancer effect with co-treatment of chemotherapeutic agent such as doxorubicin on TNBC cells (MDA-MB-231, but not in breast normal epithelia cells (MCF-10A, providing therapeutic benefits against breast tumor in the clinic.

Causes of death and competing risk analysis of the associated factors for non-small cell lung cancer using the Surveillance, Epidemiology, and End Results database.

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Wei, Shenhai; Tian, Jintao; Song, Xiaoping; Wu, Bingqun; Liu, Limin

2018-01-01

To investigate the probability of death (POD) from any causes by time after diagnosis of non-small cell lung cancer (NSCLC) and the factors associated with survival for NSCLC patients. A total of 202,914 patients with NSCLC from 2004 to 2013 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The overall survival (OS) and lung cancer-specific survival (LCSS) were calculated and POD from any causes at different time periods after diagnosis was explored. The predictive factors for OS, LCSS and survival from non-lung cancer deaths were investigated using multivariate analysis with Cox proportional hazards regression and competing risk regression analysis. The 5- and 10-year OS were 20.4% and 11.5%, accordingly that for LCSS were 25.5% and 18.4%, respectively. Lung cancer contributed 88.3% (n = 128,402) of the deaths. The POD from lung cancer decreased with time after diagnosis. In multivariate analysis, advanced age and advanced stage of NSCLC were associated with decreased OS and LCSS. Comparing to no surgery, any kind of resection conferred lower risk of death from lung cancer and higher risk of dying from non-lung cancer conditions except lobectomy or bilobectomy, which was associated with lower risk of death from both lung cancer and non-lung cancer conditions. Most of the patients with NSCLC died from lung cancer. Rational surveillance and treatment policies should be made for them. Early stage and lobectomy or bilobectomy were associated with improved OS and LCSS. It is reasonable to focus on early detection and optimal surgical treatment for NSCLC.

Medicare Spending for Breast, Prostate, Lung, and Colorectal Cancer Patients in the Year of Diagnosis and Year of Death.

Science.gov (United States)

Chen, Christopher T; Li, Ling; Brooks, Gabriel; Hassett, Michael; Schrag, Deborah

2017-07-26

To characterize spending patterns for Medicare patients with incident breast, prostate, lung, and colorectal cancer. 2007-2012 data from the Surveillance, Epidemiology, and End Results Program linked with Medicare fee-for-service claims. We calculate per-patient monthly and yearly mean and median expenditures, by cancer type, stage at diagnosis, and spending category, over the years of diagnosis and death. Over the year of diagnosis, mean spending was $35,849, $26,295, $55,597, and $63,063 for breast, prostate, lung, and colorectal cancer, respectively. Over the year of death, spending was similar across different cancer types and stage at diagnosis. Characterization of Medicare spending according to clinically meaningful categories may assist development of oncology alternative payment models and cost-effectiveness models. © Health Research and Educational Trust.

1-L-MT, an IDO inhibitor, prevented colitis-associated cancer by inducing CDC20 inhibition-mediated mitotic death of colon cancer cells.

Science.gov (United States)

Liu, Xiuting; Zhou, Wei; Zhang, Xin; Ding, Yang; Du, Qianming; Hu, Rong

2018-04-01

Indoleamine 2,3-dioxygenase 1 (IDO1), known as IDO, catabolizes tryptophan through kynurenine pathway, whose activity is correlated with impaired clinical outcome of colorectal cancer. Here we showed that 1-L-MT, a canonical IDO inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. Our results showed that inhibition of IDO decreased the transcription of CDC20, which resulted in G2/M cycle arrest of HCT-116 and HT-29. Furthermore, 1-L-MT induced mitochondria injuries and caused apoptotic cancer cells. Importantly, 1-L-MT protected mice from azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon carcinogenesis, with reduced mortality, tumor number and size. What is more, IDO1-/- mice exhibited fewer tumor burdens and reduced proliferation in the neoplastic epithelium, while, 1-L-MT did not exhibit any further protective effects on IDO-/- mice, confirming the critical role of IDO and the protective effect of 1-L-MT-mediated IDO inhibition in CRC. Furthermore, 1-L-MT also alleviated CRC in Rag1-/- mice, demonstrating the modulatory effects of IDO independent of its role in modulating adaptive immunity. Taken together, our findings validated that the anti-proliferation effect of 1-L-MT in vitro and the prevention of CRC in vivo were through IDO-induced cell cycle disaster of colon cancer cells. Our results identified 1-L-MT as a promising candidate for the chemoprevention of CRC. © 2018 UICC.

JTC801 Induces pH-dependent Death Specifically in Cancer Cells and Slows Growth of Tumors in Mice.

Science.gov (United States)

Song, Xinxin; Zhu, Shan; Xie, Yangchun; Liu, Jiao; Sun, Lingyi; Zeng, Dexing; Wang, Pengcheng; Ma, Xiaochao; Kroemer, Guido; Bartlett, David L; Billiar, Timothy R; Lotze, Michael T; Zeh, Herbert J; Kang, Rui; Tang, Daolin

2018-04-01

Maintenance of acid-base homeostasis is required for normal physiology, metabolism, and development. It is not clear how cell death is activated in response to changes in pH. We performed a screen to identify agents that induce cell death in a pH-dependent manner (we call this alkaliptosis) in pancreatic ductal adenocarcinoma cancer (PDAC) cells and tested their effects in mice. We screened a library of 254 compounds that interact with G-protein-coupled receptors (GPCRs) to identify those with cytotoxic activity against a human PDAC cell line (PANC1). We evaluated the ability of JTC801, which binds the opiod receptor and has analgesic effects, to stimulate cell death in human PDAC cell lines (PANC1, MiaPaCa2, CFPAC1, PANC2.03, BxPc3, and CAPAN2), mouse pancreatic cancer-associated stellate cell lines, primary human pancreatic ductal epithelial cells, and 60 cancer cell lines (the NCI-60 panel). Genes encoding proteins in cell death and GPCR signaling pathways, as well as those that regulate nuclear factor-κB (NF-κB) activity, were knocked out, knocked down, or expressed from transgenes in cancer cell lines. JTC801 was administered by gavage to mice with xenograft tumors, C57BL/6 mice with orthographic pancreatic tumors grown from Pdx1-Cre;KRas G12D/+ ;Tp53 R172H/+ (KPC) cells, mice with metastases following tail-vein injection of KPC cells, and Pdx-1-Cre;Kras G12D/+ mice crossed with Hmgb1 flox/flox mice (KCH mice). Pancreata were collected from mice and analyzed for tumor growth and by histology and immunohistochemistry. We compared gene and protein expression levels between human pancreatic cancer tissues and patient survival times using online R2 genomic or immunohistochemistry analyses. Exposure of human PDAC cell lines (PANC1 and MiaPaCa2) to JTC801 did not induce molecular markers of apoptosis (cleavage of caspase 3 or poly [ADP ribose] polymerase [PARP]), necroptosis (interaction between receptor-interacting serine-threonine kinase 3 [RIPK3] and mixed

20 CFR 410.679 - Finality of findings with respect to other claims for benefits based on the disability or death...

Science.gov (United States)

2010-04-01

... claims for benefits based on the disability or death of a miner. 410.679 Section 410.679 Employees..., Finality of Decisions, and Representation of Parties § 410.679 Finality of findings with respect to other claims for benefits based on the disability or death of a miner. Findings of fact made in a determination...

Inhibition of Autophagy Potentiates Atorvastatin-Induced Apoptotic Cell Death in Human Bladder Cancer Cells in Vitro

Science.gov (United States)

Kang, Minyong; Jeong, Chang Wook; Ku, Ja Hyeon; Kwak, Cheol; Kim, Hyeon Hoe

2014-01-01

Statins are cholesterol reduction agents that exhibit anti-cancer activity in several human cancers. Because autophagy is a crucial survival mechanism for cancer cells under stress conditions, cooperative inhibition of autophagy acts synergistically with other anti-cancer drugs. Thus, this study investigates whether combined treatment of atorvastatin and autophagy inhibitors results in enhancing the cytotoxic effects of atorvastatin, upon human bladder cancer cells, T24 and J82, in vitro. To measure cell viability, we performed the EZ-Cytox cell viability assay. We examined apoptosis by flow cytometry using annexin-V/propidium iodide (PI and western blot using procaspase-3 and poly (ADP-ribose) polymerase (PARP) antibodies. To examine autophagy activation, we evaluated the co-localization of LC3 and LysoTracker by immunocytochemistry, as well as the expression of LC3 and p62/sequestosome-1 (SQSTM1) by western blot. In addition, we assessed the survival and proliferation of T24 and J82 cells by a clonogenic assay. We found that atorvastatin reduced the cell viability of T24 and J82 cells via apoptotic cell death and induced autophagy activation, shown by the co-localization of LC3 and LysoTracker. Moreover, pharmacologic inhibition of autophagy significantly enhanced atorvastatin-induced apoptosis in T24 and J82 cells. In sum, inhibition of autophagy potentiates atorvastatin-induced apoptotic cell death in human bladder cancer cells in vitro, providing a potential therapeutic approach to treat bladder cancer. PMID:24815071

Second Malignant Neoplasms and Cause of Death in Patients With Germ Cell Cancer

DEFF Research Database (Denmark)

Kier, Maria G; Hansen, Merete K; Lauritsen, Jakob

2016-01-01

radiotherapy (RT); bleomycin, etoposide, and cisplatin (BEP); or more than 1 line of treatment (MTOL). Main Outcomes and Measures: Cumulative incidence and hazard ratios (HRs) for SMN and death calculated by the Cox proportional hazards model were compared with those of age-matched controls. Results: The study......Importance: Patients given systemic treatment for testicular germ cell cancer (GCC) are at increased risk for a second malignant neoplasm (SMN). Previous studies on SMN and causes of death lacked information on the exact treatment applied or were based on patients receiving former treatment options....... Objective: To evaluate the treatment-specific risks for SMN and death in a nationwide population-based cohort of patients with GCC treated with current standard regimens. Design, Setting, and Participants: This study examined a Danish nationwide cohort of 5190 men with GCC who entered the Danish Testicular...

A Combined Chemical and Magneto-Mechanical Induction of Cancer Cell Death by the Use of Functionalized Magnetic Iron Nanowires

KAUST Repository

Martinez Banderas, Aldo

2016-01-01

Cancer prevails as one of the most devastating diseases being at the top of death causes for adults despite continuous development and innovation in cancer therapy. Nanotechnology may be used to achieve therapeutic dosing, establish sustained

BID links ferroptosis to mitochondrial cell death pathways

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Sandra Neitemeier

2017-08-01

Full Text Available Ferroptosis has been defined as an oxidative and iron-dependent pathway of regulated cell death that is distinct from caspase-dependent apoptosis and established pathways of death receptor-mediated regulated necrosis. While emerging evidence linked features of ferroptosis induced e.g. by erastin-mediated inhibition of the Xc- system or inhibition of glutathione peroxidase 4 (Gpx4 to an increasing number of oxidative cell death paradigms in cancer cells, neurons or kidney cells, the biochemical pathways of oxidative cell death remained largely unclear. In particular, the role of mitochondrial damage in paradigms of ferroptosis needs further investigation.In the present study, we find that erastin-induced ferroptosis in neuronal cells was accompanied by BID transactivation to mitochondria, loss of mitochondrial membrane potential, enhanced mitochondrial fragmentation and reduced ATP levels. These hallmarks of mitochondrial demise are also established features of oxytosis, a paradigm of cell death induced by Xc- inhibition by millimolar concentrations of glutamate. Bid knockout using CRISPR/Cas9 approaches preserved mitochondrial integrity and function, and mediated neuroprotective effects against both, ferroptosis and oxytosis. Furthermore, the BID-inhibitor BI-6c9 inhibited erastin-induced ferroptosis, and, in turn, the ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 prevented mitochondrial dysfunction and cell death in the paradigm of oxytosis. These findings show that mitochondrial transactivation of BID links ferroptosis to mitochondrial damage as the final execution step in this paradigm of oxidative cell death. Keywords: Ferroptosis, BID, Mitochondria, CRISPR, Oxytosis, Neuronal death

Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

Energy Technology Data Exchange (ETDEWEB)

Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Choe, Tae-Boo [Department of Microbiological Engineering, Kon-Kuk University, Gwangjin-gu, Seoul (Korea, Republic of); Hong, Seok-Il [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Yi, Jae-Youn [Laboratory of Modulation of Radiobiological Responses, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Lee, Hyun-Gyu [Department of Microbiology and Immunology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Lee, Yun-Han, E-mail: yhlee87@yuhs.ac [Department of Radiation Oncology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Park, In-Chul, E-mail: parkic@kcch.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of)

2014-07-11

Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

Comorbidities contribute to the risk of cancer death among Aboriginal and non-Aboriginal South Australians: Analysis of a matched cohort study.

Science.gov (United States)

Banham, David; Roder, David; Brown, Alex

2018-02-01

Aboriginal Australians have poorer cancer survival than other Australians. Diagnoses at later stages and correlates of remote area living influence, but do not fully explain, these disparities. Little is known of the prevalence and influence of comorbid conditions experienced by Aboriginal people, including their effect on cancer survival. This study quantifies hospital recorded comorbidities using the Elixhauser Comorbidity Index (ECI), examines their influence on risk of cancer death, then considers effect variation by Aboriginality. Cancers diagnosed among Aboriginal South Australians in 1990-2010 (N = 777) were matched with randomly selected non-Aboriginal cases by birth year, diagnostic year, sex, and primary site, then linked to administrative hospital records to the time of diagnosis. Competing risk regression summarised associations of Aboriginal status, stage, geographic attributes and comorbidities with risk of cancer death. A threshold of four or more ECI conditions was associated with increased risk of cancer death (sub-hazard ratio SHR 1.66, 95%CI 1.11-2.46). Alternatively, the presence of any one of a subset of ECI conditions was associated with similarly increased risk (SHR = 1.62, 95%CI 1.23-2.14). The observed effects did not differ between Aboriginal and matched non-Aboriginal cases. However, Aboriginal cases experienced three times higher exposure than non-Aboriginal to four or more ECI conditions (14.2% versus 4.5%) and greater exposure to the subset of ECI conditions (20.7% versus 8.0%). Comorbidities at diagnosis increased the risk of cancer death in addition to risks associated with Aboriginality, remoteness of residence and disease stage at diagnosis. The Aboriginal cohort experienced comparatively greater exposure to comorbidities which adds to disparities in cancer outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

A prospective study of stomach cancer death in relation to green tea consumption in Japan

Science.gov (United States)

Hoshiyama, Y; Kawaguchi, T; Miura, Y; Mizoue, T; Tokui, N; Yatsuya, H; Sakata, K; Kondo, T; Kikuchi, S; Toyoshima, H; Hayakawa, N; Tamakoshi, A; Ohno, Y; Yoshimura, T

2002-01-01

To evaluate whether green tea consumption provides protection against stomach cancer death, relative risks were calculated using Cox proportional hazards regression analysis in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based on 30 370 men and 42 481 women aged 40–79. After adjustment for age, smoking status, history of peptic ulcer, family history of stomach cancer along with certain dietary items, the risks associated with drinking one or two, three or four, five to nine, and 10 or more cups of green tea per day, relative to those of drinking less than one cup per day, were 1.6 (95% CI: 0.9–2.9), 1.1 (95% CI: 0.6–1.9), 1.0 (95% CI: 0.5–2.0), and 1.0 (95% CI: 0.5–2.0), respectively, in men (P for trend=0.669), and 1.1 (95% CI: 0.5–2.5), 1.0 (95% CI: 0.5–2.5), 0.8 (95% CI: 0.4–1.6), and 0.8 (95% CI: 0.3–2.1), respectively, in women (P for trend=0.488). We found no inverse association between green tea consumption and the risk of stomach cancer death. British Journal of Cancer (2002) 87, 309–313. doi:10.1038/sj.bjc.6600487 www.bjcancer.com © 2002 Cancer Research UK PMID:12177800

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

Science.gov (United States)

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.

Child and youth cancer: profile of deaths

Directory of Open Access Journals (Sweden)

Joisy Aparecida Marchi

2013-11-01

Full Text Available This study is aimed at characterizing the deaths caused by malignant neoplasias in children and adolescents living in the state of Paraná, Brazil between 2001 and 2010. It is a quantitative, descriptive, transversal study, based on secondary data, obtained through the data processing department of the Sistema Único de Saúde from July to December, 2012. The following variables were analyzed: gender, age, race and city of residence. As a measure of association, odds ratio was used, confirmed by the χ2. The leukemia, central nervous system neoplasias and lymphomas, female gender and white race were highlight topics. Teens had about three times greater chance of dying of cancer compared to children. The child and youth neoplasia deserves special attention on the condition of vulnerability of this group, and further studies are needed to assess the association with possible risk factors.

The effectiveness of postmortem multidetector computed tomography in the detection of fatal findings related to cause of non-traumatic death in the emergency department

International Nuclear Information System (INIS)

Takahashi, Naoya; Higuchi, Takeshi; Shiotani, Motoi; Hirose, Yasuo; Shibuya, Hiroyuki; Hashidate, Hideki; Yamanouchi, Haruo; Funayama, Kazuhisa

2012-01-01

To investigate the diagnostic performance of postmortem multidetector computed tomography (PMMDCT) for the detection of fatal findings related to causes of non-traumatic death in the emergency department (ED). 494 consecutive cases of clinically diagnosed non-traumatic death in ED involving PMMDCT were enrolled. The fatal findings were detected on PMMDCT and classified as definite or possible findings. These findings were confirmed by autopsy in 20 cases. The fatal findings were detected in 188 subjects (38.1%) including 122 with definite (24.7%) and 66 with possible finding (13.4%). Definite findings included 21 cases of intracranial vascular lesions, 84 with intra-thoracic haemorrhage, 13 with retroperitoneal haemorrhage and one with oesophagogastric haemorrhage. In three patients who had initially been diagnosed with non-traumatic death, PMMDCT revealed fatal traumatic findings. Two definite findings (two haemopericardiums) and seven possible findings (two intestinal obstructions, one each of multiple liver tumours central pulmonary artery dilatation, pulmonary congestion, peritoneal haematoma, and brain oedema) were confirmed by autopsy. The causes of death were not determined in cases with possible findings without autopsy. PMMDCT is a feasible tool for detecting morphological fatal findings in non-traumatic death in ED. It is important to know the ability and limitation of PMMDCT. (orig.)

Plain radiographic findings of lung cancer with delayed diagnosis

International Nuclear Information System (INIS)

Choe, Kyu Ok; Chung, Jin Ill

1994-01-01

In Korea, Lung cancer is the Second most common prevailing malignancy among male population next to stomach cancer. Although CT scan and MRI is widely used in the staging of lung cancer, plain chest x-ray still plays an important role in screening and diagnosis. Our intention was to review the confusing radiographic features which result in delayed diagnosis of lung cancer. Of the 160 patients with lung cancer evaluated by us, 62 patients(39%) with delayed diagnosis and average diagnostic duration of 5.1 months compared with 2.1 months for those without delay. We reviewed the plain chest x-ray findings of those 62 patients. The diagnosis of lung cancer was delayed more than half of the cases under the impression of intrathoracic tuberculosis. Upon reviewing the roentgenologic findings in patients with diagnostic delay, central type appeared as a small hilar or mediastinal mass with or without obstructive pneumonia. Peripheral type appeared as an ill-defined pulmonary module, a nodule hidden by overlapping structures, or as a lung cancer associated with pulmonary tuberculosis. Some cases were misinterpreted as extranodal spread of malignancy. To solve above mentioned problems, we recommend proper understanding of natural history of lung cancer, incorporation of high kVp technique in chest radiographs, routine acquisition of lateral chest radiograph to increase diagnostic accuracy, and appropriate use of CT scan in cases of difficult diagnosis

The study of logistic regression of risk factor on the death cause of uranium miners

International Nuclear Information System (INIS)

Wen Jinai; Yuan Liyun; Jiang Ruyi

1999-01-01

Logistic regression model has widely been used in the field of medicine. The computer software on this model is popular, but it is worth to discuss how to use this model correctly. Using SPSS (Statistical Package for the Social Science) software, unconditional logistic regression method was adopted to carry out multi-factor analyses on the cause of total death, cancer death and lung cancer death of uranium miners. The data is from radioepidemiological database of one uranium mine. The result show that attained age is a risk factor in the logistic regression analyses of total death, cancer death and lung cancer death. In the logistic regression analysis of cancer death, there is a negative correlation between the age of exposure and cancer death. This shows that the younger the age at exposure, the bigger the risk of cancer death. In the logistic regression analysis of lung cancer death, there is a positive correlation between the cumulated exposure and lung cancer death, this show that cumulated exposure is a most important risk factor of lung cancer death on uranium miners. It has been documented by many foreign reports that the lung cancer death rate is higher in uranium miners

The correlation between DNA ploidy and the clinicohistologic findings in colorectal cancer

International Nuclear Information System (INIS)

Lee, Suk Ho; Kim, Hun Jung; Kim, Woo Chul; Cho, Young Kap; Loh, John J. K.; Woo, Ze Hong; Hwang, Tae Sook

2000-01-01

DNA ploidy pattern was shown to correlate with several clinicohistologic findings in several tumors. Aim of this study was to evaluate the correlation of the clinicohistologic findings in colorectal cancer and the failure pattern in rectosigmoid cancer with DNA ploidy. DNA flow cytometry using the Hedley methods on paraffin embedded specimen from 117 patients with colorectal cancers after curative resection was performed. We tried to find the correlation between DNA ploidy and various clinicohistologic findings. And then the correlation DNA ploidy and the failure pattern in 75 patients of rectosigmoid cancer was analized. Forty samples (34.2%) from tumors gave aneuploidy histogram. There was no significant difference in the frequency of DNA aneuploidy in terms of age, sex, depth of invasion, location and Dukes stage. But there was a significant correlation between DNA ploidy and the failure rates in Dukes stage B rectosigmoid cancer (p=0.048). These findings suggest that DNA ploidy pattern shows the correlation with the treatment failure rates in Dukes stage B rectosigmoid, but not with many other clinicohistologic findings. However, more patients will be needed to disclose these findings

SRT1720 induces lysosomal-dependent cell death of breast cancer cells.

Science.gov (United States)

Lahusen, Tyler J; Deng, Chu-Xia

2015-01-01

SRT1720 is an activator of SIRT1, a NAD(+)-dependent protein and histone deacetylase that plays an important role in numerous biologic processes. Several studies have illustrated that SRT1720 treatment could improve metabolic conditions in mouse models and in a study in cancer SRT1720 caused increased apoptosis of myeloma cells. However, the effect of SRT1720 on cancer may be complex, as some recent studies have demonstrated that SRT1720 may not directly activate SIRT1 and another study showed that SRT1720 treatment could promote lung metastasis. To further investigate the role of SRT1720 in breast cancer, we treated SIRT1 knockdown and control breast cancer cell lines with SRT1720 both in vitro and in vivo. We showed that SRT1720 more effectively decreased the viability of basal-type MDA-MB-231 and BT20 cells as compared with luminal-type MCF-7 breast cancer cells or nontumorigenic MCF-10A cells. We demonstrated that SRT1720 induced lysosomal membrane permeabilization and necrosis, which could be blocked by lysosomal inhibitors. In contrast, SRT1720-induced cell death occurred in vitro irrespective of SIRT1 status, whereas in nude mice, SRT1720 exhibited a more profound effect in inhibiting the growth of allograft tumors of SIRT1 proficient cells as compared with tumors of SIRT1-deficient cells. Thus, SRT1720 causes lysosomal-dependent necrosis and may be used as a therapeutic agent for breast cancer treatment. ©2014 American Association for Cancer Research.

Annonaceous acetogenin mimic AA005 induces cancer cell death via apoptosis inducing factor through a caspase-3-independent mechanism

OpenAIRE

Han, Bing; Wang, Tong-Dan; Shen, Shao-Ming; Yu, Yun; Mao, Chan; Yao, Zhu-Jun; Wang, Li-Shun

2015-01-01

Background Annonaceous acetogenins are a family of natural products with antitumor activities. Annonaceous acetogenin mimic AA005 reportedly inhibits mammalian mitochondrial NADH-ubiquinone reductase (Complex I) and induces gastric cancer cell death. However, the mechanisms underlying its cell-death-inducing activity are unclear. Methods We used SW620 colorectal adenocarcinoma cells to study AA005 cytotoxic activity. Cell deaths were determined by Trypan blue assay and flow cytometry, and rel...

Lung cancer in patients with idiopathic pulmonary fibrosis: frequency and CT findings

Energy Technology Data Exchange (ETDEWEB)

Lee, Hak Jong; Im, Jung Gi; Ahn, Joong Mo; Yeon, Kyung Mo [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

1994-12-15

The incidence of lung cancer in patients with idiopathic pulmonary fibrosis(lPF) is higher than that of general population. To evaluate the frequency and CT findings of lung cancer associated with idiopathic pulmonary fibrosis, we analyzed 19 patients with lung cancer associated with idiopathic pulmonary fibrosis. We analyzed retrospectively 19 patients with histologically confirmed lung cancer out of 208 patients diagnosed as IPF either by CT and clinical findings(n=188) or histologically(n=20). All 19 patients were male, aged 40-85 years (mean 66 years). Scanning techniques were conventional CT in 12 patients, HRCT in 1 patient and both conventional CT and HRCT in 6 patients. We analyzed the CT patterns of lung cancer and IPF, locations of the tumor and histologic types of lung cancer. The incidence of lung cancer in patients with idiopathic pulmonary fibrosis was 9.1%(19/208). In 11 of 19 patients, CT findings of lung cancer were ill-defined consolidation-like mass. Lung cancer was located mainly in lower lobes(right lower lobe; 10/19, left lower lobe; 5/19) and at the periphery(12/19). Histologically, squamous cell carcinoma was the most common cell type (11/19). The incidence of lung cancer in patients with idiopathic pulmonary fibrosis was much higher than that of general population. Typical CT findings of lung cancer were predominantly ill-defined consolidation like mass at the peripheral lung portion which is the location where the most advanced fibrosis occur.

Lung cancer in patients with idiopathic pulmonary fibrosis: frequency and CT findings

International Nuclear Information System (INIS)

Lee, Hak Jong; Im, Jung Gi; Ahn, Joong Mo; Yeon, Kyung Mo

1994-01-01

The incidence of lung cancer in patients with idiopathic pulmonary fibrosis(lPF) is higher than that of general population. To evaluate the frequency and CT findings of lung cancer associated with idiopathic pulmonary fibrosis, we analyzed 19 patients with lung cancer associated with idiopathic pulmonary fibrosis. We analyzed retrospectively 19 patients with histologically confirmed lung cancer out of 208 patients diagnosed as IPF either by CT and clinical findings(n=188) or histologically(n=20). All 19 patients were male, aged 40-85 years (mean 66 years). Scanning techniques were conventional CT in 12 patients, HRCT in 1 patient and both conventional CT and HRCT in 6 patients. We analyzed the CT patterns of lung cancer and IPF, locations of the tumor and histologic types of lung cancer. The incidence of lung cancer in patients with idiopathic pulmonary fibrosis was 9.1%(19/208). In 11 of 19 patients, CT findings of lung cancer were ill-defined consolidation-like mass. Lung cancer was located mainly in lower lobes(right lower lobe; 10/19, left lower lobe; 5/19) and at the periphery(12/19). Histologically, squamous cell carcinoma was the most common cell type (11/19). The incidence of lung cancer in patients with idiopathic pulmonary fibrosis was much higher than that of general population. Typical CT findings of lung cancer were predominantly ill-defined consolidation like mass at the peripheral lung portion which is the location where the most advanced fibrosis occur

Death Receptor-Induced Apoptosis Signalling Regulation by Ezrin Is Cell Type Dependent and Occurs in a DISC-Independent Manner in Colon Cancer Cells

Science.gov (United States)

Iessi, Elisabetta; Zischler, Luciana; Etringer, Aurélie; Bergeret, Marion; Morlé, Aymeric; Jacquemin, Guillaume; Morizot, Alexandre; Shirley, Sarah; Lalaoui, Najoua; Elifio-Esposito, Selene L.; Fais, Stefano; Garrido, Carmen; Solary, Eric; Micheau, Olivier

2015-01-01

Ezrin belongs to the ERM (ezrin-radixin-moesin) protein family and has been demonstrated to regulate early steps of Fas receptor signalling in lymphoid cells, but its contribution to TRAIL-induced cell death regulation in adherent cancer cells remains unknown. In this study we report that regulation of FasL and TRAIL-induced cell death by ezrin is cell type dependant. Ezrin is a positive regulator of apoptosis in T-lymphoma cell line Jurkat, but a negative regulator in colon cancer cells. Using ezrin phosphorylation or actin-binding mutants, we provide evidence that negative regulation of death receptor-induced apoptosis by ezrin occurs in a cytoskeleton- and DISC-independent manner, in colon cancer cells. Remarkably, inhibition of apoptosis induced by these ligands was found to be tightly associated with regulation of ezrin phosphorylation on serine 66, the tumor suppressor gene WWOX and activation of PKA. Deficiency in WWOX expression in the liver cancer SK-HEP1 or the pancreatic Mia PaCa-2 cell lines as well as WWOX silencing or modulation of PKA activation by pharmacological regulators, in the colon cancer cell line SW480, abrogated regulation of TRAIL signalling by ezrin. Altogether our results show that death receptor pro-apoptotic signalling regulation by ezrin can occur downstream of the DISC in colon cancer cells. PMID:26010871

Death Receptor-Induced Apoptosis Signalling Regulation by Ezrin Is Cell Type Dependent and Occurs in a DISC-Independent Manner in Colon Cancer Cells.

Directory of Open Access Journals (Sweden)

Elisabetta Iessi

Full Text Available Ezrin belongs to the ERM (ezrin-radixin-moesin protein family and has been demonstrated to regulate early steps of Fas receptor signalling in lymphoid cells, but its contribution to TRAIL-induced cell death regulation in adherent cancer cells remains unknown. In this study we report that regulation of FasL and TRAIL-induced cell death by ezrin is cell type dependant. Ezrin is a positive regulator of apoptosis in T-lymphoma cell line Jurkat, but a negative regulator in colon cancer cells. Using ezrin phosphorylation or actin-binding mutants, we provide evidence that negative regulation of death receptor-induced apoptosis by ezrin occurs in a cytoskeleton- and DISC-independent manner, in colon cancer cells. Remarkably, inhibition of apoptosis induced by these ligands was found to be tightly associated with regulation of ezrin phosphorylation on serine 66, the tumor suppressor gene WWOX and activation of PKA. Deficiency in WWOX expression in the liver cancer SK-HEP1 or the pancreatic Mia PaCa-2 cell lines as well as WWOX silencing or modulation of PKA activation by pharmacological regulators, in the colon cancer cell line SW480, abrogated regulation of TRAIL signalling by ezrin. Altogether our results show that death receptor pro-apoptotic signalling regulation by ezrin can occur downstream of the DISC in colon cancer cells.

Radiologic findings of male breast cancer: A case report

Energy Technology Data Exchange (ETDEWEB)

Yi, Jeong Geun; Park, Kyung Joo; Han, Chun Hwan; Lee, Joo Hyuk [Kangnam General Hospital Public Corporation, Seoul (Korea, Republic of)

1994-10-15

Male breast cancer is an uncommon disease with an incidence of 1 percent of all breast cancers. Male breast cancer usually appears as a small mass with well defined contour which is eccentrically located in relation to the nipple on mammogram. We report a case of breast cancer in a 51 year old man with mammographic appearance of large hyperdense mass with nipple inversion and axillary lymphadenopathy, gray-scale sonographic finding of homogeneous solid mass and multiple tumor vessels within the mass on color Doppler ultrasound.

Development of a statistical model for cervical cancer cell death with irreversible electroporation in vitro.

Science.gov (United States)

Yang, Yongji; Moser, Michael A J; Zhang, Edwin; Zhang, Wenjun; Zhang, Bing

2018-01-01

The aim of this study was to develop a statistical model for cell death by irreversible electroporation (IRE) and to show that the statistic model is more accurate than the electric field threshold model in the literature using cervical cancer cells in vitro. HeLa cell line was cultured and treated with different IRE protocols in order to obtain data for modeling the statistical relationship between the cell death and pulse-setting parameters. In total, 340 in vitro experiments were performed with a commercial IRE pulse system, including a pulse generator and an electric cuvette. Trypan blue staining technique was used to evaluate cell death after 4 hours of incubation following IRE treatment. Peleg-Fermi model was used in the study to build the statistical relationship using the cell viability data obtained from the in vitro experiments. A finite element model of IRE for the electric field distribution was also built. Comparison of ablation zones between the statistical model and electric threshold model (drawn from the finite element model) was used to show the accuracy of the proposed statistical model in the description of the ablation zone and its applicability in different pulse-setting parameters. The statistical models describing the relationships between HeLa cell death and pulse length and the number of pulses, respectively, were built. The values of the curve fitting parameters were obtained using the Peleg-Fermi model for the treatment of cervical cancer with IRE. The difference in the ablation zone between the statistical model and the electric threshold model was also illustrated to show the accuracy of the proposed statistical model in the representation of ablation zone in IRE. This study concluded that: (1) the proposed statistical model accurately described the ablation zone of IRE with cervical cancer cells, and was more accurate compared with the electric field model; (2) the proposed statistical model was able to estimate the value of electric

Assessment of programmed death-ligand 1 expression and tumor-associated immune cells in pediatric cancer tissues.

Science.gov (United States)

Majzner, Robbie G; Simon, Jason S; Grosso, Joseph F; Martinez, Daniel; Pawel, Bruce R; Santi, Mariarita; Merchant, Melinda S; Geoerger, Birgit; Hezam, Imene; Marty, Virginie; Vielh, Phillippe; Daugaard, Mads; Sorensen, Poul H; Mackall, Crystal L; Maris, John M

2017-10-01

Programmed death 1 (PD-1) signaling in the tumor microenvironment dampens immune responses to cancer, and blocking this axis induces antitumor effects in several malignancies. Clinical studies of PD-1 blockade are only now being initiated in pediatric patients, and little is known regarding programmed death-ligand 1 (PD-L1) expression in common childhood cancers. The authors characterized PD-L1 expression and tumor-associated immune cells (TAICs) (lymphocytes and macrophages) in common pediatric cancers. Whole slide sections and tissue microarrays were evaluated by immunohistochemistry for PD-L1 expression and for the presence of TAICs. TAICs were also screened for PD-L1 expression. Thirty-nine of 451 evaluable tumors (9%) expressed PD-L1 in at least 1% of tumor cells. The highest frequency histotypes comprised Burkitt lymphoma (80%; 8 of 10 tumors), glioblastoma multiforme (36%; 5 of 14 tumors), and neuroblastoma (14%; 17 of 118 tumors). PD-L1 staining was associated with inferior survival among patients with neuroblastoma (P = .004). Seventy-four percent of tumors contained lymphocytes and/or macrophages. Macrophages were significantly more likely to be identified in PD-L1-positive versus PD-L1-negative tumors (P cancers exhibit PD-L1 expression, whereas a much larger fraction demonstrates infiltration with tumor-associated lymphocytes. PD-L1 expression may be a biomarker for poor outcome in neuroblastoma. Further preclinical and clinical investigation will define the predictive nature of PD-L1 expression in childhood cancers both at diagnosis and after exposure to chemoradiotherapy. Cancer 2017;123:3807-3815. © 2017 American Cancer Society. © 2017 American Cancer Society.

Average annual doses, lifetime doses and associated risk of cancer death for radiation workers in various fuel fabrication facilities in India

International Nuclear Information System (INIS)

Iyer, P.S.; Dhond, R.V.

1980-01-01

Lifetime doses based on average annual doses are estimated for radiation workers in various fuel fabrication facilities in India. For such cumulative doses, the risk of radiation-induced cancer death is computed. The methodology for arriving at these estimates and the assumptions made are discussed. Based on personnel monitoring records from 1966 to 1978, the average annual dose equivalent for radiation workers is estimated as 0.9 mSv (90 mrem), and the maximum risk of cancer death associated with this occupational dose as 1.35x10 -5 a -1 , as compared with the risk of death due to natural causes of 7x10 -4 a -1 and the risk of death due to background radiation alone of 1.5x10 -5 a -1 . (author)

Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney didease and end-stage renal disease

DEFF Research Database (Denmark)

Ørskov, Bjarne; Sørensen, Vibeke Rømming; Feldt-Rasmussen, Bo Friis

2012-01-01

Abstract Background. With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31...... December 2008. Methods. Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular...... (HR) 0.65, P = 0.008] and deaths from cerebrovascular disease decreased by 69% (HR 0.31, P = 0.0003) from the first to the second time period. There were no significant changes between the time periods in death from cancer, infection, other or unknown. From the first to the second 8-year interval...

Causes of death in familial adenomatous polyposis

DEFF Research Database (Denmark)

Galle, T S; Juel, K; Bülow, S

1999-01-01

The prognosis in familial adenomatous polyposis (FAP) has improved over the past decades owing to a reduction in the prevalence of colorectal cancer, resulting from effective early screening. During the same period several polyposis registers have recorded an increasing number of deaths due to du...... to duodenal/periampullary cancer and desmoid tumours. The aim of this study was to examine the causes of death with special emphasis on duodenal/periampullary cancer.......The prognosis in familial adenomatous polyposis (FAP) has improved over the past decades owing to a reduction in the prevalence of colorectal cancer, resulting from effective early screening. During the same period several polyposis registers have recorded an increasing number of deaths due...

Anabolic Androgenic Steroid (AAS) related deaths: autoptic, histopathological and toxicological findings.

Science.gov (United States)

Frati, Paola; Busardò, Francesco P; Cipolloni, Luigi; Dominicis, Enrico De; Fineschi, Vittorio

2015-01-01

Anabolic androgenic steroids (AASs) represent a large group of synthetic derivatives of testosterone, produced to maximize anabolic effects and minimize the androgenic ones. AAS can be administered orally, parenterally by intramuscular injection and transdermally. Androgens act by binding to the nuclear androgen receptor (AR) in the cytoplasm and then translocate into the nucleus. This binding results in sequential conformational changes of the receptor affecting the interaction between receptor and protein, and receptor and DNA. Skeletal muscle can be considered as the main target tissue for the anabolic effects of AAS, which are mediated by ARs which after exposure to AASs are up-regulated and their number increases with body building. Therefore, AASs determine an increase in muscle size as a consequence of a dose-dependent hypertrophy resulting in an increase of the cross-sectional areas of both type I and type II muscle fibers and myonuclear domains. Moreover, it has been reported that AASs can increase tolerance to exercise by making the muscles more capable to overload therefore shielding them from muscle fiber damage and improving the level of protein synthesis during recovery. Despite some therapeutic use of AASs, there is also wide abuse among athletes especially bodybuilders in order to improve their performances and to increase muscle growth and lean body mass, taking into account the significant anabolic effects of these drugs. The prolonged misuse and abuse of AASs can determine several adverse effects, some of which may be even fatal especially on the cardiovascular system because they may increase the risk of sudden cardiac death (SCD), myocardial infarction, altered serum lipoproteins, and cardiac hypertrophy. The aim of this review is to focus on deaths related to AAS abuse, trying to evaluate the autoptic, histopathological and toxicological findings in order to investigate the pathophysiological mechanism that underlines this type of death, which

Cancer incidence in atomic bomb survivors. Part IV: Comparison of cancer incidence and mortality

International Nuclear Information System (INIS)

Ron, E.; Preston, D.L.; Mabuchi, Kiyohiko; Thompson, D.E.; Soda, Midori

1994-01-01

This report compares cancer incidence and mortality among atomic bomb survivors in the Radiation Effects Research Foundation Life Span Study (LSS) cohort. Because the incidence data are derived from the Hiroshima and Nagasaki tumor registries, case ascertainment is limited to the time (1958-1987) and geographic restrictions (Hiroshima and Nagasaki) of the registries, whereas mortality data are available from 1950-1987 anywhere in Japan. With these conditions, there were 9,014 first primary incident cancer cases identified among LSS cohort members compared with 7,308 deaths for which cancer was listed as the underlying cause of death on death certificates. When deaths were limited to those occurring between 1958-1987 in Hiroshima or Nagasaki, there were 3,155 more incident cancer cases overall, and 1,262 more cancers of the digestive system. For cancers of the oral cavity and pharynx, skin, breast, female and male genital organs, urinary system and thyroid, the incidence series was at least twice as large as the comparable mortality series. Although the incidence and mortality data are dissimilar in many ways, the overall conclusions regarding which solid cancers provide evidence of a significant dose response generally confirm the mortality findings. When either incidence or mortality data are evaluated, significant excess risks are observed for all solid cancers, stomach, colon, liver (when it is defined as primary liver cancer or liver cancer not otherwise specified on the death certificate), lung, breast, ovary and urinary bladder. No significant radiation effect is seen for cancers of the pharynx, rectum, gallbladder, pancreas, nose, larynx, uterus, prostate or kidney in either series. There is evidence of a significant excess of nonmelanoma skin cancer in the incidence data, but not in the mortality series. 19 refs., 2 figs., 10 tabs

Novel histone deacetylase inhibitor CG200745 induces clonogenic cell death by modulating acetylation of p53 in cancer cells.

Science.gov (United States)

Oh, Eun-Taex; Park, Moon-Taek; Choi, Bo-Hwa; Ro, Seonggu; Choi, Eun-Kyung; Jeong, Seong-Yun; Park, Heon Joo

2012-04-01

Histone deacetylase (HDAC) plays an important role in cancer onset and progression. Therefore, inhibition of HDAC offers potential as an effective cancer treatment regimen. CG200745, (E)-N(1)-(3-(dimethylamino)propyl)-N(8)-hydroxy-2-((naphthalene-1-loxy)methyl)oct-2-enediamide, is a novel HDAC inhibitor presently undergoing a phase I clinical trial. Enhancement of p53 acetylation by HDAC inhibitors induces cell cycle arrest, differentiation, and apoptosis in cancer cells. The purpose of the present study was to investigate the role of p53 acetylation in the cancer cell death caused by CG200745. CG200745-induced clonogenic cell death was 2-fold greater in RKO cells expressing wild-type p53 than in p53-deficient RC10.1 cells. CG200745 treatment was also cytotoxic to PC-3 human prostate cancer cells, which express wild-type p53. CG200745 increased acetylation of p53 lysine residues K320, K373, and K382. CG200745 induced the accumulation of p53, promoted p53-dependent transactivation, and enhanced the expression of MDM2 and p21(Waf1/Cip1) proteins, which are encoded by p53 target genes. An examination of CG200745 effects on p53 acetylation using cells transfected with various p53 mutants showed that cells expressing p53 K382R mutants were significantly resistant to CG200745-induced clonogenic cell death compared with wild-type p53 cells. Moreover, p53 transactivation in response to CG200745 was suppressed in all cells carrying mutant forms of p53, especially K382R. Taken together, these results suggest that acetylation of p53 at K382 plays an important role in CG200745-induced p53 transactivation and clonogenic cell death.

Patient survival and tumor characteristics associated with CHEK2:p.I157T - findings from the Breast Cancer Association Consortium

DEFF Research Database (Denmark)

Muranen, Taru A; Blomqvist, Carl; Dörk, Thilo

2016-01-01

BACKGROUND: P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival...... and characteristics of breast tumors of germ line p.I157T carriers. METHODS: We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer...... characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models...

Variations in the quality and costs of end-of-life care, preferences and palliative outcomes for cancer patients by place of death: the QUALYCARE study

Directory of Open Access Journals (Sweden)

Koffman Jonathan

2010-08-01

Full Text Available Abstract Background Emerging trends and new policies suggest that more cancer patients might die at home in the future. However, not all have equal chances of achieving this. Furthermore, there is lack of evidence to support that those who die at home experience better care and a better death than those who die as inpatients. The QUALYCARE study aims to examine variations in the quality and costs of end-of-life care, preferences and palliative outcomes associated with dying at home or in an institution for cancer patients. Methods/Design Mortality followback survey (with a nested case-control study of home vs. hospital deaths conducted with bereaved relatives of cancer patients in four Primary Care Trusts in London. Potential participants are identified from death registrations and approached by the Office for National Statistics in complete confidence. Data are collected via a postal questionnaire to identify the informal and formal care received in the three months before death and the associated costs, relatives' satisfaction with care, and palliative outcomes for the patients and their relatives. A well-established questionnaire to measure relatives' views on the care integrates four brief and robust tools - the Client Service Receipt Inventory, the Palliative Outcome Scale, the EQ-5 D and the Texas Revised Inventory of Grief. Further questions assess patients and relatives' preferences for place of death. The survey aims to include 500 bereaved relatives (140 who experienced a home death, 205 a hospital death, 115 a hospice death and 40 a nursing home death. Bivariate and multivariate analyses will explore differences in place of death and place of end-of-life care, in preferences for place of death, patients' palliative outcomes and relatives' bereavement outcomes, in relation to place of death. Factors influencing death at home and the costs of end-of-life care by place of death will be identified. Discussion Collecting data on end

International study of the place of death of people with cancer: a population-level comparison of 14 countries across 4 continents using death certificate data

NARCIS (Netherlands)

Cohen, J.; Pivodic, L.; Miccinesi, G.; Onwuteaka-Philipsen, B.D.; Naylor, W.A.; Wilson, D.M.; Loucka, M.; Csikos, A.; Pardon, K.; Block, L.; Ruiz-Ramos, M.; Cardenas-Turanzas, M.; Rhee, Y.; Aubry, R.; Hunt, K.; Teno, J.; Houttekier, D.; Deliens, L.

2015-01-01

Background:Where people die can influence a number of indicators of the quality of dying. We aimed to describe the place of death of people with cancer and its associations with clinical, socio-demographic and healthcare supply characteristics in 14 countries.Methods:Cross-sectional study using

False Negative Mammogram of Breast Cancer : Analysis of Mammographic and Sonographic Findings and Correlation with Clinical Findings

International Nuclear Information System (INIS)

Lee, Kil Jun; Lee, Ji Yeon; Han, Sung Nim; Jeong, Seong Ki; Tae, Seok; Shin, Kyoung Ja; Lee, Sang Chun

1995-01-01

Recent mammographic equipment have been of good quality and yielded high diagnostic accuracy for the detection of breast cancer. However, negative mammogram does not necessarily rule out breast cancer. Therefore were viewed cause of false negative mammography in confirmed breast cancer to improve diagnostic accuracy and for adequate clinical approach. We reviewed 19 cases of confirmed breast cancer, which showed false negative mammography with positive sonographic findings. Retrospective analysis was done by correlating the patient's age, sonographic finding and mass size, mammographic breast pattern and cause of false negative mammogram, and clinical symptoms. Among the 5 patients below 35 years in age, mass was not visible due to dense breast in 4 and due to small size in 1 case. In 14 patients over 35 years in age, 11 had normal mammographic findings, 4 had dense breast, and 7 had small sized mass. Remaining 3 cases showed asymmetric density in 2 and architecture distortion in 1 case. All showed mass lesion in sonography : ill defined malignant appearance in 14,well defined malignant appearance in 2, and well defined benign in 3 cases. Negative mammogram should be correlated with sonography in case of dense breast, below 35 years in age with palpable mass and under risk for breast cancer

Tug of War between Survival and Death: Exploring ATM Function in Cancer

Science.gov (United States)

Stagni, Venturina; Oropallo, Veronica; Fianco, Giulia; Antonelli, Martina; Cinà, Irene; Barilà, Daniela

2014-01-01

Ataxia-telangiectasia mutated (ATM) kinase is a one of the main guardian of genome stability and plays a central role in the DNA damage response (DDR). The deregulation of these pathways is strongly linked to cancer initiation and progression as well as to the development of therapeutic approaches. These observations, along with reports that identify ATM loss of function as an event that may promote tumor initiation and progression, point to ATM as a bona fide tumor suppressor. The identification of ATM as a positive modulator of several signalling networks that sustain tumorigenesis, including oxidative stress, hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation, raise the question of whether ATM function in cancer may be more complex. This review aims to give a complete overview on the work of several labs that links ATM to the control of the balance between cell survival, proliferation and death in cancer. PMID:24681585

Tug of War between Survival and Death: Exploring ATM Function in Cancer

Directory of Open Access Journals (Sweden)

Venturina Stagni

2014-03-01

Full Text Available Ataxia-telangiectasia mutated (ATM kinase is a one of the main guardian of genome stability and plays a central role in the DNA damage response (DDR. The deregulation of these pathways is strongly linked to cancer initiation and progression as well as to the development of therapeutic approaches. These observations, along with reports that identify ATM loss of function as an event that may promote tumor initiation and progression, point to ATM as a bona fide tumor suppressor. The identification of ATM as a positive modulator of several signalling networks that sustain tumorigenesis, including oxidative stress, hypoxia, receptor tyrosine kinase and AKT serine-threonine kinase activation, raise the question of whether ATM function in cancer may be more complex. This review aims to give a complete overview on the work of several labs that links ATM to the control of the balance between cell survival, proliferation and death in cancer.

Antiproliferation and induction of cell death of Phaffia rhodozyma (Xanthophyllomyces dendrorhous) extract fermented by brewer malt waste on breast cancer cells.

Science.gov (United States)

Teo, Ivy Tuang Ngo; Chui, Chung Hin; Tang, Johnny Cheuk On; Lau, Fung Yi; Cheng, Gregory Yin Ming; Wong, Raymond Siu Ming; Kok, Stanton Hon Lung; Cheng, Chor Hing; Chan, Albert Sun Chi; Ho, Kwok Ping

2005-11-01

Astaxanthin has been shown to have antiproliferative activity on breast cancer and skin cancer cells. However, the high cost of production, isolation and purification of purified astaxanthin from natural sources or chemically synthetic methods limit its usage on cancer therapy. We show that astaxanthin could be produced by fermentating the Phaffia rhodozyma (Xanthophyllomyces dendrorhous) yeast cells with brewer malt waste using a 20 L B. Braun fermentor. The percentage composition of astaxanthin from the P. rhodozyma was >70% of total pigment as estimated by the high performance liquid chromatographic analysis. Furthermore, the antiproliferative activity of this P. rhodozyma cell extract (PRE) was demonstrated on breast cancer cell lines including the MCF-7 (estrogen receptor positive) and MDA-MB231 (estrogen receptor negative) by using the [3-(4,5-dimethylthiazol-2-yl)-5-(3-arboxymethoxyphenyl)-2- (4-sulfophenyl)-2H-tetrazolium] (MTS) assay. No apoptotic cell death, but growth inhibitory effect was induced after 48 h of PRE incubation as suggested by morphological investigation. Anchorage-dependent clonogenicity assay showed that PRE could reduce the colony formation potential of both breast cancer cell lines. Cell death was observed from both breast cancer cell lines after incubation with PRE for 6 days. Taken together, our results showed that by using an economic method of brewer malt waste fermentation, we obtained P. rhodozyma with a high yield of astaxanthin and the corresponding PRE could have short-term growth inhibition and long-term cell death activity on breast cancer cells.

Cigarette smoking, alcohol drinking and the risk of gallbladder cancer death: a prospective cohort study in Japan.

Science.gov (United States)

Yagyu, Kiyoko; Kikuchi, Shogo; Obata, Yuki; Lin, Yingsong; Ishibashi, Teruo; Kurosawa, Michiko; Inaba, Yutaka; Tamakoshi, Akiko

2008-02-15

Gallbladder cancer is a rare cancer with a poor prognosis, and few risk factors have been identified to date. This prospective study was conducted to evaluate the association of cigarette smoking and alcohol consumption with the risk of gallbladder cancer death. A baseline survey in 45 areas throughout Japan was conducted from 1988 to 1990 using a self-administered questionnaire, and a total of 113,496 participants (65,740 women) aged 40-89 years at entry were followed for 15 years. During the follow-up period, 165 gallbladder cancer deaths (95 women) were observed. Among women, the hazard ratio (HR) [95 percent confidence interval: 95% CI] of current smoker was 2.00 [0.91-4.42], when adjusted for age and drinking. There was no clear association between alcohol consumption and the risk. Among men, HR of current smoker was 2.27 [1.05-4.90]. HRs of those who smoked 21 cigarettes or more per day and those with 801-1,000 cigarette-years were 3.18 [1.18-8.53] and 3.44 [1.40-8.45], respectively, and positive linear associations were observed between that risk and the number of cigarettes per day (p for trend = 0.007) or "cigarette-years" (p for trend = 0.012). The alcohol dose was linearly associated with risk (p for trend = 0.004), where the HR among those who consumed 72.0 g or more of alcohol per day was 3.60 [1.29-9.85]. Among both men and women, cigarette smoking may elevate the risk of death from gallbladder cancer. Drinking may pose an elevated risk among men, but that seems to be less true among women. (c) 2007 Wiley-Liss, Inc.

Tumor necrosis factor (TNF) biology and cell death.

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Bertazza, Loris; Mocellin, Simone

2008-01-01

Tumor necrosis factor (TNF) was the first cytokine to be used in humans for cancer therapy. However, its role in the treatment of cancer patients is debated. Most uncertainties in this field stem from the knowledge that the pathways directly activated or indirectly affected upon TNF engagement with its receptors can ultimately lead to very different outcomes in terms of cell survival. In this article, we summarize the fundamental molecular biology aspects of this cytokine. Such a basis is a prerequisite to critically approach the sometimes conflicting preclinical and clinical findings regarding the relationship between TNF, tumor biology and anticancer therapy. Although the last decade has witnessed remarkable advances in this field, we still do not know in detail how cells choose between life and death after TNF stimulation. Understanding this mechanism will not only shed new light on the physiological significance of TNF-driven programmed cell death but also help investigators maximize the anticancer potential of this cytokine.

Anticancer Effect of Ginger Extract against Pancreatic Cancer Cells Mainly through Reactive Oxygen Species-Mediated Autotic Cell Death

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Akimoto, Miho; Iizuka, Mari; Kanematsu, Rie; Yoshida, Masato; Takenaga, Keizo

2015-01-01

The extract of ginger (Zingiber officinale Roscoe) and its major pungent components, [6]-shogaol and [6]-gingerol, have been shown to have an anti-proliferative effect on several tumor cell lines. However, the anticancer activity of the ginger extract in pancreatic cancer is poorly understood. Here, we demonstrate that the ethanol-extracted materials of ginger suppressed cell cycle progression and consequently induced the death of human pancreatic cancer cell lines, including Panc-1 cells. The underlying mechanism entailed autosis, a recently characterized form of cell death, but not apoptosis or necroptosis. The extract markedly increased the LC3-II/LC3-I ratio, decreased SQSTM1/p62 protein, and enhanced vacuolization of the cytoplasm in Panc-1 cells. It activated AMPK, a positive regulator of autophagy, and inhibited mTOR, a negative autophagic regulator. The autophagy inhibitors 3-methyladenine and chloroquine partially prevented cell death. Morphologically, however, focal membrane rupture, nuclear shrinkage, focal swelling of the perinuclear space and electron dense mitochondria, which are unique morphological features of autosis, were observed. The extract enhanced reactive oxygen species (ROS) generation, and the antioxidant N-acetylcystein attenuated cell death. Our study revealed that daily intraperitoneal administration of the extract significantly prolonged survival (P = 0.0069) in a peritoneal dissemination model and suppressed tumor growth in an orthotopic model of pancreatic cancer (P < 0.01) without serious adverse effects. Although [6]-shogaol but not [6]-gingerol showed similar effects, chromatographic analyses suggested the presence of other constituent(s) as active substances. Together, these results show that ginger extract has potent anticancer activity against pancreatic cancer cells by inducing ROS-mediated autosis and warrants further investigation in order to develop an efficacious candidate drug. PMID:25961833

Anticancer Effect of Ginger Extract against Pancreatic Cancer Cells Mainly through Reactive Oxygen Species-Mediated Autotic Cell Death.

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Miho Akimoto

Full Text Available The extract of ginger (Zingiber officinale Roscoe and its major pungent components, [6]-shogaol and [6]-gingerol, have been shown to have an anti-proliferative effect on several tumor cell lines. However, the anticancer activity of the ginger extract in pancreatic cancer is poorly understood. Here, we demonstrate that the ethanol-extracted materials of ginger suppressed cell cycle progression and consequently induced the death of human pancreatic cancer cell lines, including Panc-1 cells. The underlying mechanism entailed autosis, a recently characterized form of cell death, but not apoptosis or necroptosis. The extract markedly increased the LC3-II/LC3-I ratio, decreased SQSTM1/p62 protein, and enhanced vacuolization of the cytoplasm in Panc-1 cells. It activated AMPK, a positive regulator of autophagy, and inhibited mTOR, a negative autophagic regulator. The autophagy inhibitors 3-methyladenine and chloroquine partially prevented cell death. Morphologically, however, focal membrane rupture, nuclear shrinkage, focal swelling of the perinuclear space and electron dense mitochondria, which are unique morphological features of autosis, were observed. The extract enhanced reactive oxygen species (ROS generation, and the antioxidant N-acetylcystein attenuated cell death. Our study revealed that daily intraperitoneal administration of the extract significantly prolonged survival (P = 0.0069 in a peritoneal dissemination model and suppressed tumor growth in an orthotopic model of pancreatic cancer (P < 0.01 without serious adverse effects. Although [6]-shogaol but not [6]-gingerol showed similar effects, chromatographic analyses suggested the presence of other constituent(s as active substances. Together, these results show that ginger extract has potent anticancer activity against pancreatic cancer cells by inducing ROS-mediated autosis and warrants further investigation in order to develop an efficacious candidate drug.

Alpha-tocopheryl succinate inhibits autophagic survival of prostate cancer cells induced by vitamin K3 and ascorbate to trigger cell death.

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Marco Tomasetti

Full Text Available BACKGROUND: The redox-silent vitamin E analog α-tocopheryl succinate (α-TOS was found to synergistically cooperate with vitamin K3 (VK3 plus ascorbic acid (AA in the induction of cancer cell-selective apoptosis via a caspase-independent pathway. Here we investigated the molecular mechanism(s underlying cell death induced in prostate cancer cells by α-TOS, VK3 and AA, and the potential use of targeted drug combination in the treatment of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: The generation of ROS, cellular response to oxidative stress, and autophagy were investigated in PC3 prostate cancer cells by using drugs at sub-toxic doses. We evaluated whether PARP1-mediated apoptosis-inducing factor (AIF release plays a role in apoptosis induced by the combination of the agents. Next, the effect of the combination of α-TOS, VK3 and AA on tumor growth was examined in nude mice. VK3 plus AA induced early ROS formation associated with induction of autophagy in response to oxidative stress, which was reduced by α-TOS, preventing the formation of autophagosomes. α-TOS induced mitochondrial destabilization leading to the release of AIF. Translocation of AIF from mitochondria to the nucleus, a result of the combinatorial treatment, was mediated by PARP1 activation. The inhibition of AIF as well as of PARP1 efficiently attenuated apoptosis triggered by the drug combination. Using a mouse model of prostate cancer, the combination of α-TOS, VK3 and AA was more efficient in tumor suppression than when the drugs were given separately, without deleterious side effects. CONCLUSIONS/SIGNIFICANCE: α-TOS, a mitochondria-targeting apoptotic agent, switches at sub-apoptotic doses from autophagy-dependent survival of cancer cells to their demise by promoting the induction of apoptosis. Given the grim prognosis for cancer patients, this finding is of potential clinical relevance.

Dignity, death, and dilemmas: a study of Washington hospices and physician-assisted death.

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Campbell, Courtney S; Black, Margaret A

2014-01-01

The legalization of physician-assisted death in states such as Washington and Oregon has presented defining ethical issues for hospice programs because up to 90% of terminally ill patients who use the state-regulated procedure to end their lives are enrolled in hospice care. The authors recently partnered with the Washington State Hospice and Palliative Care Organization to examine the policies developed by individual hospice programs on program and staff participation in the Washington Death with Dignity Act. This article sets a national and local context for the discussion of hospice involvement in physician-assisted death, summarizes the content of hospice policies in Washington State, and presents an analysis of these findings. The study reveals meaningful differences among hospice programs about the integrity and identity of hospice and hospice care, leading to different policies, values, understandings of the medical procedure, and caregiving practices. In particular, the authors found differences 1) in the language used by hospices to refer to the Washington statute that reflect differences among national organizations, 2) the values that hospice programs draw on to support their policies, 3) dilemmas created by requests by patients for hospice staff to be present at a patient's death, and 4) five primary levels of noninvolvement and participation by hospice programs in requests from patients for physician-assisted death. This analysis concludes with a framework of questions for developing a comprehensive hospice policy on involvement in physician-assisted death and to assist national, state, local, and personal reflection. Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Jaspine B induces nonapoptotic cell death in gastric cancer cells independently of its inhibition of ceramide synthase.

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Cingolani, Francesca; Simbari, Fabio; Abad, Jose Luis; Casasampere, Mireia; Fabrias, Gemma; Futerman, Anthony H; Casas, Josefina

2017-08-01

Sphingolipids (SLs) have been extensively investigated in biomedical research due to their role as bioactive molecules in cells. Here, we describe the effect of a SL analog, jaspine B (JB), a cyclic anhydrophytosphingosine found in marine sponges, on the gastric cancer cell line, HGC-27. JB induced alterations in the sphingolipidome, mainly the accumulation of dihydrosphingosine, sphingosine, and their phosphorylated forms due to inhibition of ceramide synthases. Moreover, JB provoked atypical cell death in HGC-27 cells, characterized by the formation of cytoplasmic vacuoles in a time and dose-dependent manner. Vacuoles appeared to originate from macropinocytosis and triggered cytoplasmic disruption. The pan-caspase inhibitor, z-VAD, did not alter either cytotoxicity or vacuole formation, suggesting that JB activates a caspase-independent cell death mechanism. The autophagy inhibitor, wortmannin, did not decrease JB-stimulated LC3-II accumulation. In addition, cell vacuolation induced by JB was characterized by single-membrane vacuoles, which are different from double-membrane autophagosomes. These findings suggest that JB-induced cell vacuolation is not related to autophagy and it is also independent of its action on SL metabolism. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Docetaxel-induced prostate cancer cell death involves concomitant activation of caspase and lysosomal pathways and is attenuated by LEDGF/p75

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Leoh Lai

2009-08-01

Full Text Available Abstract Background Hormone-refractory prostate cancer (HRPC is characterized by poor response to chemotherapy and high mortality, particularly among African American men when compared to other racial/ethnic groups. It is generally accepted that docetaxel, the standard of care for chemotherapy of HRPC, primarily exerts tumor cell death by inducing mitotic catastrophe and caspase-dependent apoptosis following inhibition of microtubule depolymerization. However, there is a gap in our knowledge of mechanistic events underlying docetaxel-induced caspase-independent cell death, and the genes that antagonize this process. This knowledge is important for circumventing HRPC chemoresistance and reducing disparities in prostate cancer mortality. Results We investigated mechanistic events associated with docetaxel-induced death in HRPC cell lines using various approaches that distinguish caspase-dependent from caspase-independent cell death. Docetaxel induced both mitotic catastrophe and caspase-dependent apoptosis at various concentrations. However, caspase activity was not essential for docetaxel-induced cytotoxicity since cell death associated with lysosomal membrane permeabilization still occurred in the presence of caspase inhibitors. Partial inhibition of docetaxel-induced cytotoxicity was observed after inhibition of cathepsin B, but not inhibition of cathepsins D and L, suggesting that docetaxel induces caspase-independent, lysosomal cell death. Simultaneous inhibition of caspases and cathepsin B dramatically reduced docetaxel-induced cell death. Ectopic expression of lens epithelium-derived growth factor p75 (LEDGF/p75, a stress survival autoantigen and transcription co-activator, attenuated docetaxel-induced lysosomal destabilization and cell death. Interestingly, LEDGF/p75 overexpression did not protect cells against DTX-induced mitotic catastrophe, and against apoptosis induced by tumor necrosis factor related apoptosis inducing ligand (TRAIL

FastStats: Leading Causes of Death

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... Submit What's this? Submit Button NCHS Home Leading Causes of Death Recommend on Facebook Tweet Share Compartir Data are for the U.S. Number of deaths for leading causes of death Heart disease: 633,842 • Cancer: 595,930 • Chronic ...

A three-protein biomarker panel assessed in diagnostic tissue predicts death from prostate cancer for men with localized disease

International Nuclear Information System (INIS)

Severi, Gianluca; FitzGerald, Liesel M; Muller, David C; Pedersen, John; Longano, Anthony; Southey, Melissa C; Hopper, John L; English, Dallas R; Giles, Graham G; Mills, John

2014-01-01

Only a minority of prostate cancers lead to death. Because no tissue biomarkers of aggressiveness other than Gleason score are available at diagnosis, many nonlethal cancers are treated aggressively. We evaluated whether a panel of biomarkers, associated with a range of disease outcomes in previous studies, could predict death from prostate cancer for men with localized disease. Using a case-only design, subjects were identified from three Australian epidemiological studies. Men who had died of their disease, “cases” (N = 83), were matched to “referents” (N = 232), those who had not died of prostate cancer, using incidence density sampling. Diagnostic tissue was retrieved to assess expression of AZGP1, MUC1, NKX3.1, p53, and PTEN by semiquantitative immunohistochemistry (IHC). Poisson regression was used to estimate mortality rate ratios (MRRs) adjusted for age, Gleason score, and stage and to estimate survival probabilities. Expression of MUC1 and p53 was associated with increased mortality (MRR 2.51, 95% CI 1.14–5.54, P = 0.02 and 3.08, 95% CI 1.41–6.95, P = 0.005, respectively), whereas AZGP1 expression was associated with decreased mortality (MRR 0.44, 95% CI 0.20–0.96, P = 0.04). Analyzing all markers under a combined model indicated that the three markers were independent predictors of prostate cancer death and survival. For men with localized disease at diagnosis, assessment of AZGP1, MUC1, and p53 expression in diagnostic tissue by IHC could potentially improve estimates of risk of dying from prostate cancer based only on Gleason score and clinical stage

Causes of adult female deaths in Bangladesh: findings from two National Surveys.

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Nahar, Quamrun; El Arifeen, Shams; Jamil, Kanta; Streatfield, Peter Kim

2015-09-18

Assessment of causes of death and changes in pattern of causes of death over time are needed for programmatic purposes. Limited national level data exist on the adult female causes of death in Bangladesh. Using data from two nationally representation surveys, the 2001 and 2010 Bangladesh Maternal Mortality Surveys (BMMS), the paper examines the causes of adult female death, aged 15-49 years, and changes in the patterns of these deaths. In both surveys, all household deaths three years prior to the survey were identified. Adult female deaths were then followed by a verbal autopsy (VA) using the WHO structured questionnaire. Two physicians independently reviewed the VA forms to assign a cause of death using the ICD-10; in case of disagreement, a third physician made an independent review and assigned a cause of death. The overall mortality rates for women aged 15-49 in 2001 and 2010 were 182 per 100,000 and 120 per 100,000 respectively. There is a shift in the pattern of causes of death during the period covered by the two surveys. In the 2001 survey, the main causes of death were maternal (20 %), followed by diseases of the circulatory system (15 %), malignancy (14 %) and infectious diseases (13 %). However, in the 2010 survey, malignancies were the leading cause (21 %), followed by diseases of the circulatory system (16 %), maternal causes (14 %) and infectious diseases (8 %). While maternal deaths remained the number one cause of death among 20-34 years old in both surveys, unnatural deaths were the main cause for teenage deaths, and malignancies were the main cause of death for older women. Although there is an increasing trend in the proportion of women who died in hospitals, in both surveys most women died at home (74 % in 2001 and 62 % in 2010). The shift in the pattern of causes of adult female deaths is in agreement with the overall change in the disease pattern from communicable to non-communicable diseases in Bangladesh. Suicide and other violent deaths as

Recovering missing mesothelioma deaths in death certificates using hospital records.

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Santana, Vilma S; Algranti, Eduardo; Campos, Felipe; Cavalcante, Franciana; Salvi, Leonardo; Santos, Simone A; Inamine, Rosemeire N; Souza, William; Consonni, Dario

2018-04-02

In Brazil, underreporting of mesothelioma and cancer of the pleura (MCP) is suspected to be high. Records from death certificates (SIM) and hospital registers (SIH-SUS) can be combined to recover missing data but only anonymous databases are available. This study shows how common data can be used for linkage and as an assessment of accuracy. Mesothelioma (all sites, ICD-10 codes C45.0-C45.9) and cancer of the pleura (C38.4) were retrieved from both information systems and combined using a linkage algorithm. Accuracy was examined with non-anonymous databases, limited to the state of São Paulo. We found 775 cases in death certificates and 283 in hospital registers. The linkage matched 57 cases, all accurately paired. Three cases, 0.4% in SIM and 1.3% in SIH-SUS, could not be matched because of data inconsistencies. A computer linkage can recover MCP cases from hospital records not found in death certificates in Brazil. © 2018 Wiley Periodicals, Inc.

Hope, Life, and Death: A Qualitative Analysis of Dying Cancer Patients' Talk about Hope

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Eliott, Jaklin A.; Olver, Ian N.

2009-01-01

Although deemed vital to patient well-being, hope in persons who are terminally ill is often thought to be problematic, particularly when centered on cure. As part of a study on end-of-life decision-making, we asked 28 patients with cancer, believed to be within weeks of their death, to talk about hope. Responses were transcribed and discursively…

BID links ferroptosis to mitochondrial cell death pathways.

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Neitemeier, Sandra; Jelinek, Anja; Laino, Vincenzo; Hoffmann, Lena; Eisenbach, Ina; Eying, Roman; Ganjam, Goutham K; Dolga, Amalia M; Oppermann, Sina; Culmsee, Carsten

2017-08-01

Ferroptosis has been defined as an oxidative and iron-dependent pathway of regulated cell death that is distinct from caspase-dependent apoptosis and established pathways of death receptor-mediated regulated necrosis. While emerging evidence linked features of ferroptosis induced e.g. by erastin-mediated inhibition of the X c - system or inhibition of glutathione peroxidase 4 (Gpx4) to an increasing number of oxidative cell death paradigms in cancer cells, neurons or kidney cells, the biochemical pathways of oxidative cell death remained largely unclear. In particular, the role of mitochondrial damage in paradigms of ferroptosis needs further investigation. In the present study, we find that erastin-induced ferroptosis in neuronal cells was accompanied by BID transactivation to mitochondria, loss of mitochondrial membrane potential, enhanced mitochondrial fragmentation and reduced ATP levels. These hallmarks of mitochondrial demise are also established features of oxytosis, a paradigm of cell death induced by X c - inhibition by millimolar concentrations of glutamate. Bid knockout using CRISPR/Cas9 approaches preserved mitochondrial integrity and function, and mediated neuroprotective effects against both, ferroptosis and oxytosis. Furthermore, the BID-inhibitor BI-6c9 inhibited erastin-induced ferroptosis, and, in turn, the ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 prevented mitochondrial dysfunction and cell death in the paradigm of oxytosis. These findings show that mitochondrial transactivation of BID links ferroptosis to mitochondrial damage as the final execution step in this paradigm of oxidative cell death. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis

NARCIS (Netherlands)

Janssen-Heijnen, M. L. G.; van Erning, F. N.; De Ruysscher, D. K.; Coebergh, J. W. W.; Groen, H. J. M.

Background: Many patients with non-small cell lung cancer (NSCLC) die within the first few years of diagnosis, and considerable excess mortality remains even after 5 years. We investigated the death rate and the distribution of causes of death for NSCLC patients by age and stage at diagnosis during

Belief in life after death and mental health: findings from a national survey.

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Flannelly, Kevin J; Koenig, Harold G; Ellison, Christopher G; Galek, Kathleen; Krause, Neal

2006-07-01

The present study examined the association between belief in life after death and six measures of psychiatric symptomology in a national sample of 1403 adult Americans. A statistically significant inverse relationship was found between belief in life after death and symptom severity on all six symptom clusters that were examined (i.e., anxiety, depression, obsession-compulsion, paranoia, phobia, and somatization) after controlling for demographic and other variables (e.g., stress and social support) that are known to influence mental health. No significant association was found between the frequency of attending religious services and any of the mental health measures. The results are discussed in terms of the potentially salubrious effects of religious belief systems on mental health. These findings suggest that it may be more valuable to focus on religious beliefs than on religious practices and behaviors in research on religion and mental health.

A survey of occupational cancer in the rubber and cablemaking industries: analysis of deaths occurring in 1972-74.

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Fox, A J; Collier, P F

1976-11-01

The records of 40 867 men employed for at least one year in the rubber and cablemaking industries have now been observed for eight years. This analysis compares the mortality pattern for 1972-74 with that previously reported for 1968-71. It indicates a significant excess of deaths due to cancer of the bladder throughout the industry including men who had not been exposed to acknowledged bladder carcinogens. This excess is in deaths occurring in 1973 and 1974 in the 45-64 and 65 years plus age groups. The two sectors of the industry where this excess is significant are footwear and footwear supplies except adhesives, and the tyre sector. The excess of all cancers taken together previously noted throughout the study population for 1968-71 is confirmed for 1972-74 as is the excess for lung cancers. The greater excess in the tyre sector is also confirmed, particularly in those men in the 55-64 year age group and those who entered the industry between 1950 and 1960. While men employed in 1967 on moulding, press, autoclave, and pan curing, and workers in finished goods, stores, packaging, and despatch continue to have more lung cancer deaths than expected for 1972-74, the excess is no longer statistically significant. An excess of cancer of the stomach which was overlooked in 1968-71 is not confirmed in 1972-74 but is nevertheless high when the total period of study 1968-74 is considered. The limitations of the study are discussed with particular reference to extrapolating the results to the whole industry. We conclude that there is a higher rate of lung cancer in the tyre sector of the industry and that immediate investigations are required to test the hypothesis concerning the recent excess of bladder cancers. Attention should now be paid to the control of exposures to all potential hazards in the industry.

Meaning of life, representation of death, and their association with psychological distress.

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Testoni, Ines; Sansonetto, Giulia; Ronconi, Lucia; Rodelli, Maddalena; Baracco, Gloria; Grassi, Luigi

2017-08-09

This paper presents a two-phase cross-sectional study aimed at examining the possible mitigating role of perceived meaning of life and representation of death on psychological distress, anxiety, and depression. The first phase involved 219 healthy participants, while the second encompassed 30 cancer patients. Each participant completed the Personal Meaning Profile (PMP), the Testoni Death Representation Scale (TDRS), the Hospital Anxiety and Depression Scale (HADS), and the Distress Thermometer (DT). The primary analyses comprised (1) correlation analyses between the overall scores of each of the instruments and (2) path analysis to assess the indirect effect of the PMP on DT score through anxiety and depression as determined by the HADS. The path analysis showed that the PMP was inversely correlated with depression and anxiety, which, in turn, mediated the effect on distress. Inverse correlations were found between several dimensions of the PMP, the DT, and the HADS-Anxiety and HADS-Depression subscales, in both healthy participants and cancer patients. Religious orientation (faith in God) was related to a stronger sense of meaning in life and the ontological representation of death as a passage, rather than annihilation. Our findings support the hypothesis that participants who represent death as a passage and have a strong perception of the meaning of life tend to report lower levels of distress, anxiety, and depression. We recommend that perceived meaning of life and representation of death be more specifically examined in the cancer and palliative care settings.

Significance of apoptotic cell death after γ-irradiation

International Nuclear Information System (INIS)

Wu, H.G.; Kim, I.H.; Ha, S.W.; Park, C.I.

2003-01-01

Full text: The objectives of this study are to investigate the significance of apoptotic death compared to total cell death after γ-ray irradiation in human Hand N cancer cell lines and to find out correlation between apoptosis and radiation sensitivity. Materials and Method: Head and neck cancer cell lines (PCI-1, PCI-13, and SNU-1066), leukemia cell line (CCRF-CEM), and fibroblast cell line (LM217) as a normal control were used for this study. Cells were irradiated using Cs-137 animal experiment irradiator. Total cell death was measured by clonogenic assay. Annexin-V staining was used to detect the fraction of apoptotic death. The resulting data was analyzed with two parameters, apoptotic index (AI) and apoptotic fraction(AF). AI is ratio of apoptotic cells to total cells, and AF is ration of apoptotic cell death to mutant frequencytion ex(Number of apoptotic cells) / (Number of total cells counted) AF = {(AI) / (1-survival fraction)} x 100 (%) Results. Surviving fraction at 2 Gy (SF2) were 0.741, 0.544, 0.313, 0.302, and 0.100 for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217 cell lines, respectively. Apoptosis was detected in all cell lines. Apoptotic index reached peak value at 72 hours after irradiation in head and neck cancer cell lines, and that was at 24 hours in CCRF-CEM and LM217. Total cell death increased exponentially with increasing radiation dose from 0 Gy to 8 Gy, but the change was minimal in apoptotic index (Fig. 1.). Apoptotic fractions at 2 Gy were 46%, 48%, 46%, 24%, and 19% and at 6 Gy were 20%, 33%, 35%, 17%, and 20% for PCI-1, PCI-13, SNU-1066, CCRF-CEM, and LM217, respectively. The radioresistant cell lines showed more higher apoptotic fraction at 2 Gy (Table 1.), but there was not such correlation at 6 Gy. Conclusion: All cell lines used in this study showed apoptosis after irradiation, but time course of apoptosis was different from that of leukemia cell line and normal fibroblast cell line. Reproductive cell death was more important

Nuclear DAMP complex-mediated RAGE-dependent macrophage cell death

Energy Technology Data Exchange (ETDEWEB)

Chen, Ruochan [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Fu, Sha; Fan, Xue-Gong [Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Lotze, Michael T.; Zeh, Herbert J. [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Tang, Daolin, E-mail: tangd2@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Kang, Rui, E-mail: kangr@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States)

2015-03-13

High mobility group box 1 (HMGB1), histone, and DNA are essential nuclear components involved in the regulation of chromosome structure and function. In addition to their nuclear function, these molecules act as damage-associated molecular patterns (DAMPs) alone or together when released extracellularly. The synergistic effect of these nuclear DNA-HMGB1-histone complexes as DAMP complexes (nDCs) on immune cells remains largely unexplored. Here, we demonstrate that nDCs limit survival of macrophages (e.g., RAW264.7 and peritoneal macrophages) but not cancer cells (e.g., HCT116, HepG2 and Hepa1-6). nDCs promote production of inflammatory tumor necrosis factor α (TNFα) release, triggering reactive oxygen species-dependent apoptosis and necrosis. Moreover, the receptor for advanced glycation end products (RAGE), but not toll-like receptor (TLR)-4 and TLR-2, was required for Akt-dependent TNFα release and subsequent cell death following treatment with nDCs. Genetic depletion of RAGE by RNAi, antioxidant N-Acetyl-L-cysteine, and TNFα neutralizing antibody significantly attenuated nDC-induced cell death. These findings provide evidence supporting novel signaling mechanisms linking nDCs and inflammation in macrophage cell death. - Highlights: • Nuclear DAMP complexes (nDCs) selectively induce cell death in macrophages, but not cancer cells. • TNFα-mediated oxidative stress is required for nDC-induced death. • RAGE-mediated Akt activation is required for nDC-induced TNFα release. • Blocking RAGE and TNFα inhibits nDC-induced macrophage cell death.

JS-K, a nitric oxide-releasing prodrug, induces breast cancer cell death while sparing normal mammary epithelial cells.

Science.gov (United States)

McMurtry, Vanity; Saavedra, Joseph E; Nieves-Alicea, René; Simeone, Ann-Marie; Keefer, Larry K; Tari, Ana M

2011-04-01

Targeted therapy with reduced side effects is a major goal in cancer research. We investigated the effects of JS-K, a nitric oxide (NO) prodrug designed to release high levels of NO when suitably activated, on human breast cancer cell lines, on non-transformed human MCF-10A mammary cells, and on normal human mammary epithelial cells (HMECs). Cell viability assay, flow cytometry, electron microscopy, and Western blot analysis were used to study the effects of JS-K on breast cancer and on mammary epithelial cells. After a 3-day incubation, the IC50s of JS-K against the breast cancer cells ranged from 0.8 to 3 µM. However, JS-K decreased the viability of the MCF-10A cells by only 20% at 10-µM concentration, and HMECs were unaffected by 10 µM JS-K. Flow cytometry indicated that JS-K increased the percentages of breast cancer cells under-going apoptosis. Interestingly, flow cytometry indicated that JS-K increased acidic vesicle organelle formation in breast cancer cells, suggesting that JS-K induced autophagy in breast cancer cells. Electron microscopy confirmed that JS-K-treated breast cancer cells underwent autophagic cell death. Western blot analysis showed that JS-K induced the expression of microtubule light chain 3-II, another autophagy marker, in breast cancer cells. However, JS-K did not induce apoptosis or autophagy in normal human mammary epithelial cells. These data indicate that JS-K selectively induces programmed cell death in breast cancer cells while sparing normal mammary epithelial cells under the same conditions. The selective anti-tumor activity of JS-K warrants its further investigation in breast tumors.

Primary Causes of Death After Permanent Prostate Brachytherapy

International Nuclear Information System (INIS)

Bittner, Nathan; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Wallner, Kent E.; Allen, Zachariah A.; Brammer, Sarah G.; Moyad, Mark

2008-01-01

Purpose: To evaluate the primary causes of death in low-risk (low-risk), intermediate-risk (intermediate-risk), and high-risk (high-risk) patients undergoing permanent prostate brachytherapy with or without supplemental therapies. Methods and Materials: From April 1995 through November 2004, a total of 1,354 consecutive patients underwent prostate brachytherapy. All patients underwent brachytherapy >3 years before analysis. Of the patients, 532 (39.3%) received androgen deprivation therapy and 703 (51.9%) received supplemental radiation therapy. The median follow-up was 5.4 years. Multiple parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. Results: The 10-year cause-specific survival was 97.0% (99.7%, 99.0%, and 90.1% for low-risk, intermediate-risk, and high-risk patients). Overall survival was 76.7% (82.5%, 78.3%, and 67.6% for low-, intermediate-, and high-risk patients, respectively). The cumulative death rate for cardiovascular disease was 11.5% (8.7%, 9.3%, and 19.8% for low-, intermediate-, and high-risk patients). The death rate from second malignancies (nonprostate cancer) was 7.2% and was not substantially different when stratified by risk group. Death from all other causes was 6.5% for the entire cohort but 1.3%, 5.0%, and 10.8% for low-, intermediate-, and high-risk patients. In multivariate analysis, death from prostate cancer was best predicted by Gleason score and risk group, whereas death from cardiovascular disease, nonprostate cancer, and all other causes were most closely related to patient age and tobacco use. Conclusions: Although cardiovascular mortality was the predominant cause of death, prostate cancer was responsible for approximately 10% of all deaths. In particular, overall survival was poorest in the high-risk group. Although high-risk patients were most likely to die of prostate cancer, the divergence in overall survival between high-risk and lower-risk patients primarily

Oxidative stress activates the TRPM2-Ca2+-CaMKII-ROS signaling loop to induce cell death in cancer cells.

Science.gov (United States)

Wang, Qian; Huang, Lihong; Yue, Jianbo

2017-06-01

High intracellular levels of reactive oxygen species (ROS) cause oxidative stress that results in numerous pathologies, including cell death. Transient potential receptor melastatin-2 (TRPM2), a Ca 2+ -permeable cation channel, is mainly activated by intracellular adenosine diphosphate ribose (ADPR) in response to oxidative stress. Here we studied the role and mechanisms of TRPM2-mediated Ca 2+ influx on oxidative stress-induced cell death in cancer cells. We found that oxidative stress activated the TRPM2-Ca 2+ -CaMKII cascade to inhibit early autophagy induction, which ultimately led to cell death in TRPM2 expressing cancer cells. On the other hand, TRPM2 knockdown switched cells from cell death to autophagy for survival in response to oxidative stress. Moreover, we found that oxidative stress activated the TRPM2-CaMKII cascade to further induce intracellular ROS production, which led to mitochondria fragmentation and loss of mitochondrial membrane potential. In summary, our data demonstrated that oxidative stress activates the TRPM2-Ca 2+ -CaMKII-ROS signal loop to inhibit autophagy and induce cell death. Copyright © 2016 Elsevier B.V. All rights reserved.

Conceptual modeling of postmortem evaluation findings to describe dairy cow deaths.

Science.gov (United States)

McConnel, C S; Garry, F B; Hill, A E; Lombard, J E; Gould, D H

2010-01-01

Dairy cow mortality levels in the United States are excessive and increasing over time. To better define cause and effect and combat rising mortality, clearer definitions of the reasons that cows die need to be acquired through thorough necropsy-based postmortem evaluations. The current study focused on organizing information generated from postmortem evaluations into a monitoring system that is based on the fundamentals of conceptual modeling and that will potentially be translatable into on-farm relational databases. This observational study was conducted on 3 high-producing, commercial dairies in northern Colorado. Throughout the study period a thorough postmortem evaluation was performed by veterinarians on cows that died on each dairy. Postmortem data included necropsy findings, life-history features (e.g., birth date, lactation number, lactational and reproductive status), clinical history and treatments, and pertinent aspects of operational management that were subject to change and considered integral to the poor outcome. During this study, 174 postmortem evaluations were performed. Postmortem evaluation results were conceptually modeled to view each death within the context of the web of factors influencing the dairy and the cow. Categories were formulated describing mortality in terms of functional characteristics potentially amenable to easy performance evaluation, management oversight, and research. In total, 21 death categories with 7 category themes were created. Themes included specific disease processes with variable etiologies, failure of disease recognition or treatment, traumatic events, multifactorial failures linked to transition or negative energy balance issues, problems with feed management, miscellaneous events not amenable to prevention or treatment, and undetermined causes. Although postmortem evaluations provide the relevant information necessary for framing a cow's death, a restructuring of on-farm databases is needed to integrate this

Parental Grief Following the Death of a Child from Cancer: The Ongoing Odyssey.

Science.gov (United States)

Snaman, Jennifer M; Kaye, Erica C; Torres, Carlos; Gibson, Deborah; Baker, Justin N

2016-09-01

The death of a child is a devastating event that results in profound grief and significant psychosocial and physical morbidities in parents. The parental grief journey is a complex phenomenon necessitating the utilization of newer models of bereavement with a focus on relationships and exploration of parents' perceived meanings of the experience. To further characterize the grief journey of parents whose child died from cancer in order to better identify parents who can benefit from additional bereavement support and design strategies to improve bereavement services for these parents. We conducted focus group sessions with 11 bereaved parents. The parents were given two prompts to describe their grief journey before and after their child's death, and their responses in a narrative form were audio-recorded. The responses were coded and studied independently by semantic content analysis. Collation and analysis of the coded responses to both prompts results in the emergence of four concepts from the parental narratives: (1) description of the grief trajectory and evolution of grief over time, (2) mechanisms of parental coping throughout the grief journey, (3) factors that exacerbate parental grief, and (4) sources of parental support throughout the grief journey. The narratives highlighted that parents whose child died of cancer experience a unique and evolving form of grief and they wish to continue their bond with the deceased child. We recommend that healthcare providers and institutions incorporate support systems into a comprehensive bereavement program for families of children who die from cancer. © 2016 Wiley Periodicals, Inc.

Breast cancer survival rate according to data of cancer registry and death registry systems in Bushehr province, 2001-2013

Directory of Open Access Journals (Sweden)

Zahra Rampisheh

2015-09-01

Full Text Available Background: Breast cancer is the most common female cancer worldwide. Survival rate of breast cancer, especially as an indicator of the successful implementation of screening, diagnosis and treatment programs, has been at the center of attention of public health experts Material and Methods: In a survival study, the records of breast cancer cases in cancer registry system of Bushehr Province were extracted during 2001, March to 2013, September. These records were linked and matched with records of death registry system. After determining patients, status regarding being alive or dead, survival analysis was done. Life table, Kaplan-Mayer analysis, log rank and Breslow tests were used for computing and comparing survival rates. Results: In 300 recorded breast cancer cases, mean and standard deviation of age was 51.26±13.87. Survival rates were 95, 88, 78, 73 and 68 percent since the first year through the fifth year, respectively. Mean survival was 87.20 months (95% CI= 81.28- 93.12. There was no significant difference in mean survival regarding age and different geographical areas. Conclusion: Although survival rates of registered breast cancer patients in Bushehr Province are similar to other provinces, they are far from those of developed countries. This situation demands more extensive efforts regarding public education and improving the process of diagnosis, treatment and care of patients especially during first two years after diagnosis.

Cell death triggered by alpha-emitting 213Bi-immunoconjugates in HSC45-M2 gastric cancer cells is different from apoptotic cell death

International Nuclear Information System (INIS)

Seidl, Christof; Schroeck, Hedwig; Seidenschwang, Sabine; Beck, Roswitha; Schwaiger, Markus; Senekowitsch-Schmidtke, Reingard; Schmid, Ernst; Abend, Michael; Becker, Karl-Friedrich; Apostolidis, Christos; Nikula, Tuomo K.; Kremmer, Elisabeth

2005-01-01

Radioimmunotherapy with α-particle-emitting nuclides, such as 213 Bi, is a promising concept for the elimination of small tumour nodules or single disseminated tumour cells. The aim of this study was to investigate cellular damage and the mode of cell death triggered by 213 Bi-immunoconjugates. Human gastric cancer cells (HSC45-M2) expressing d9-E-cadherin were incubated with different levels of activity of 213 Bi-d9MAb targeting d9-E-cadherin and 213 Bi-d8MAb, which does not bind to d9-E-cadherin. Micronucleated (M) cells, abnormal (A) cells and apoptotic (A) [(MAA)] cells were scored microscopically in the MAA assay following fluorescent staining of nuclei and cytoplasm. Chromosomal aberrations were analysed microscopically following Giemsa staining. The effect of z-VAD-fmk, known to inhibit apoptosis, on the prevention of cell death was investigated following treatment of HSC45-M2 cells with sorbitol as well as 213 Bi-d9MAb. Activation of caspase 3 after incubation of HSC45-M2 cells with both sorbitol and 213 Bi-d9MAb was analysed via Western blotting. Following incubation of HSC45-M2 human gastric cancer cells expressing d9-E-cadherin with 213 Bi-d9MAb the number of cells killed increased proportional to the applied activity concentration. Microscopically visible effects of α-irradiation of HSC45-M2 cells were formation of micronuclei and severe chromosomal aberrations. Preferential induction of these lesions with specific 213 Bi-d9MAb compared with unspecific 213 Bi-d8MAb (not targeting d9-E-cadherin) was not observed if the number of floating, i.e. unbound 213 Bi-immunoconjugates per cell exceeded 2 x 10 4 , most likely due to intense crossfire. In contrast to sorbitol-induced cell death, cell death triggered by 213 Bi-immunoconjugates was independent of caspase 3 activation and could not be inhibited by z-VAD-fmk, known to suppress the apoptotic pathway. 213 Bi-immunoconjugates seem to induce a mode of cell death different from apoptosis in HSC45-M2 cells

Audit of practice in sudden unexpected death in epilepsy (SUDEP) post mortems and neuropathological findings.

Science.gov (United States)

Thom, Maria; Michalak, Zuzanna; Wright, Gabriella; Dawson, Timothy; Hilton, David; Joshi, Abhijit; Diehl, Beate; Koepp, Matthias; Lhatoo, Samden; Sander, Josemir W; Sisodiya, Sanjay M

2016-08-01

Sudden unexpected death in epilepsy (SUDEP) is one of the leading causes of death in people with epilepsy. For classification of definite SUDEP, a post mortem (PM), including anatomical and toxicological examination, is mandatory to exclude other causes of death. We audited PM practice as well as the value of brain examination in SUDEP. We reviewed 145 PM reports in SUDEP cases from four UK neuropathology centres. Data were extracted for clinical epilepsy details, circumstances of death and neuropathological findings. Macroscopic brain abnormalities were identified in 52% of cases. Mild brain swelling was present in 28%, and microscopic pathologies relevant to cause or effect of seizures were seen in 89%. Examination based on whole fixed brains (76.6% of all PMs), and systematic regional sampling was associated with higher detection rates of underlying pathology (P detection of relevant pathology. Availability of full clinical epilepsy-related information at the time of PM could potentially further improve detection through targeted tissue sampling. Apart from confirmation of SUDEP, complete neuropathological examination contributes to evaluation of risk factors as well as helping to direct future research into underlying causes. © 2015 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.

Validation of verbal autopsy: determination of cause of deaths in Malaysia 2013.

Science.gov (United States)

Ganapathy, Shubash Shander; Yi Yi, Khoo; Omar, Mohd Azahadi; Anuar, Mohamad Fuad Mohamad; Jeevananthan, Chandrika; Rao, Chalapati

2017-08-11

Mortality statistics by age, sex and cause are the foundation of basic health data required for health status assessment, epidemiological research and formation of health policy. Close to half the deaths in Malaysia occur outside a health facility, are not attended by medical personnel, and are given a lay opinion as to the cause of death, leading to poor quality of data from vital registration. Verbal autopsy (VA) is a very useful tool in diagnosing broad causes of deaths for events that occur outside health facilities. This article reports the development of the VA methods and our principal finding from a validation study. A cross sectional study on nationally representative sample deaths that occurred in Malaysia during 2013 was used. A VA questionnaire suitable for local use was developed. Trained field interviewers visited the family members of the deceased at their homes and conducted face to face interviews with the next of kin. Completed questionnaires were reviewed by trained physicians who assigned multiple and underlying causes. Reference diagnoses for validation were obtained from review of medical records (MR) available for a sample of the overall study deaths. Corresponding MR diagnosis with matched sample of the VA diagnosis were available in 2172 cases for the validation study. Sensitivity scores were good (>75%) for transport accidents and certain cancers. Moderate sensitivity (50% - 75%) was obtained for ischaemic heart disease (64%) and cerebrovascular disease (72%). The validation sample for deaths due to major causes such as ischaemic heart disease, pneumonia, breast cancer and transport accidents show low cause-specific mortality fraction (CSMF) changes. The scores obtained for the top 10 leading site-specific cancers ranged from average to good. We can conclude that VA is suitable for implementation for deaths outside the health facilities in Malaysia. This would reduce ill-defined mortality causes in vital registration data, and yield more

Data study of death rate and cancer incidence among Thule workers, 2005; Registerundersoegelse af doedelighed og kraeftforekomst blandt Thulearbejdere, 2005

Energy Technology Data Exchange (ETDEWEB)

Juel, K. [Statens Insti. for Folkesundhed, Copenhagen (Denmark); Engholm, G.; Storm, H. [Kraeftens Bekaempelse, Copenhagen (Denmark)

2005-12-01

January 21st, 1968, an American B52 bomber with nuclear weapons aboard crashed close to the Thule air-base in Greenland. In 1986 suspicions arose that there might be increased disease incidences and death rate among the employees at the base that were involved in the clearing operations. During 1986 - 1995, several health studies were made of the Thule workers. These studies of death rate, cancer, hospitalization, and fertility did not show any differences between the Thule workers from the clearing operations and those not involved in the clearing. The present study shows no difference in total death rate among the clearing workers compared to other workers. The same results were found for cancer mortality, circulatory diseases, pulmonary diseases, natural causes, and accidents. As the previous studies showed, the present study shows that there were a slightly less number of suicides among the clearing workers. The data analyses show with great certainty that the Thule workers as a group do not have a great excessive mortality or an increased cancer incidence caused by the aircraft crash. Thus, the present results fall in line with the previous investigations. (ln)

Perceived efficacy, conscious fear of death and intentions to tan: not all fear appeals are created equal.

Science.gov (United States)

Cooper, Douglas P; Goldenberg, Jamie L; Arndt, Jamie

2014-02-01

According to the terror management health model, conscious thoughts of death motivate productive health behaviours when the targeted behaviour is perceived as an effective route for mitigating the threat and removing death-related thought from focal awareness. The present study thus examined whether messages manipulating the efficacy of a health behaviour moderate health outcomes when participants are presented with a fear appeal that makes death thought conscious. A 3 (fear appeal: cancer vs. appearance vs. neutral) × 2 (delay vs. no delay) × 2 (effective vs. non-effective) between-subjects ANOVA was conducted. Beach patrons were randomly assigned to a cancer, appearance, or neutral-threat fear appeal followed by a delay or no delay. Subsequently, they read messages highlighting the effectiveness or ineffectiveness of sun protection behaviours and reported their intentions to engage in those behaviours. When fear appeals primed conscious thoughts of death, framing sun protection as ineffective decreased sun protection intentions relative to framing sun protection as effective. In contrast, fear appeals that did not consciously prime death, or appeals followed by a delay that allowed thoughts of death to fade from consciousness, did not interact with efficacy messages. The findings revealed that messages impacting sun protection efficacy moderated sun protection intentions only when death was conscious. The findings have implications for understanding the conditions that render certain fear appeals, and accompanying messages of efficacy, more influential than others. © 2013 The British Psychological Society.

Near-Death Experiences and the "Fantasy-Prone" Personality: Preliminary Findings.

Science.gov (United States)

Council, James R.; Greyson, Bruce

Near-death experiences (NDEs) are subjective experiences at the threshold of death which can include strong positive affect, dissociation from the physical body, and paranormal/transcendental phenomena. Empirical investigation of NDEs has typically relied upon retrospective reports and personality studies of individuals who have come close to…

Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis.

Science.gov (United States)

Fonseca, B M; Correia-da-Silva, G; Teixeira, N A

2018-05-01

Among a variety of phytocannabinoids, Δ 9 -tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most promising therapeutic compounds. Besides the well-known palliative effects in cancer patients, cannabinoids have been shown to inhibit in vitro growth of tumor cells. Likewise, the major endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), induce tumor cell death. The purpose of the present study was to characterize cannabinoid elements and evaluate the effect of cannabinoids in endometrial cancer cell viability. The presence of cannabinoid receptors, transient receptor potential vanilloid 1 (TRPV1), and endocannabinoid-metabolizing enzymes were determined by qRT-PCR and Western blot. We also examined the effects and the underlying mechanisms induced by eCBs and phytocannabinoids in endometrial cancer cell viability. Besides TRPV1, both EC cell lines express all the constituents of the endocannabinoid system. We observed that at concentrations higher than 5 μM, eCBs and CBD induced a significant reduction in cell viability in both Ishikawa and Hec50co cells, whereas THC did not cause any effect. In Ishikawa cells, contrary to Hec50co, treatment with AEA and CBD resulted in an increase in the levels of activated caspase -3/-7, in cleaved PARP, and in reactive oxygen species generation, confirming that the reduction in cell viability observed in the MTT assay was caused by the activation of the apoptotic pathway. Finally, these effects were dependent on TRPV1 activation and intracellular calcium levels. These data indicate that cannabinoids modulate endometrial cancer cell death. Selective targeting of TPRV1 by AEA, CBD, or other stable analogues may be an attractive research area for the treatment of estrogen-dependent endometrial carcinoma. Our data further support the evaluation of CBD and CBD-rich extracts for the potential treatment of endometrial cancer, particularly, that has become non-responsive to common therapies.

Musa paradisiaca inflorescence induces human colon cancer cell death by modulating cascades of transcriptional events.

Science.gov (United States)

K B, Arun; Madhavan, Aravind; T R, Reshmitha; Thomas, Sithara; Nisha, P

2018-01-24

Colorectal cancer (CRC) is one of the leading causes of cancer death, and diet plays an important role in the etiology of CRC. Traditional medical practitioners in many South Asian countries use plantain inflorescence to treat various gastro-intestinal ailments. The aim of the present study was to investigate the anticancer effects of extracts of inflorescence of Musa paradisiaca against HT29 human colon cancer cells and elucidate the mechanism of these effects by studying the modulation of cascades of transcriptional events. In vitro assays depicted that methanol extract of Musa paradisiaca inflorescence (PIMET) was cytotoxic to HT29 cells. PIMET induced DNA damage and arrested the cell cycle at the G2/M phase. Expression studies showed that PIMET pretreatment upregulates pro-apoptotic Bcl2 and downregulates anti-apoptotic Bax proteins. Different assays showed that the deregulation of pro/antiapoptotic proteins reduces the mitochondrial membrane potential and ATP production; moreover, it enhances cytochrome c release, which triggers the apoptotic pathway, and further cleaves caspase 3 and PARP proteins, resulting in apoptosis. Changes in the protein expression profile of HT29 cells after PIMET treatment were analyzed using mass-spectrometry-based proteomics. PIMET treatment significantly altered the expression of HT29 protein; interestingly, X-linked inhibitor of apoptosis protein was also downregulated. Alteration in the expression of this protein has significant effects, leading to HT29 cell death.

Neoadjuvant chemotherapy for breast cancer: correlation between the baseline MR imaging findings and responses to therapy

International Nuclear Information System (INIS)

Uematsu, Takayoshi; Yuen, Sachiko; Kasami, Masako

2010-01-01

To retrospectively evaluate the magnetic resonance (MR) imaging findings of breast cancer before neoadjuvant chemotherapy (NAC) and to compare findings of chemosensitive breast cancer with those of chemoresistant breast cancer. The MR imaging findings before NAC in 120 women undergoing NAC were reviewed. The MR imaging findings were compared with the pathological findings and responses. A complete response (pCR) and marked response were achieved in 12 and 35% of 120 breast cancers in 120 women respectively. Breast cancers with a pCR or marked response were classified as chemosensitive breast cancer. The remaining 64 breast cancers (53%) were classified as chemoresistant breast cancer. Large tumour size, a lesion without mass effect, and very high intratumoural signal intensity on T2-weighted MR images were significantly associated with chemoresistant breast cancer. Lesions with mass effect and washout enhancement pattern were significantly associated with chemosensitive breast cancer. Areas with very high intratumoural signal intensity on T2-weighted images corresponded pathologically to areas of intratumoural necrosis. Several MR imaging features of breast cancer before NAC can help predict the efficacy of NAC. (orig.)

Neoadjuvant chemotherapy for breast cancer: correlation between the baseline MR imaging findings and responses to therapy

Energy Technology Data Exchange (ETDEWEB)

Uematsu, Takayoshi; Yuen, Sachiko [Shizuoka Cancer Center Hospital, Breast Imaging and Breast Intervention Section, Naga-izumi, Shizuoka (Japan); Kasami, Masako [Shizuoka Cancer Center Hospital, Department of Pathology, Naga-izumi, Shizuoka (Japan)

2010-10-15

To retrospectively evaluate the magnetic resonance (MR) imaging findings of breast cancer before neoadjuvant chemotherapy (NAC) and to compare findings of chemosensitive breast cancer with those of chemoresistant breast cancer. The MR imaging findings before NAC in 120 women undergoing NAC were reviewed. The MR imaging findings were compared with the pathological findings and responses. A complete response (pCR) and marked response were achieved in 12 and 35% of 120 breast cancers in 120 women respectively. Breast cancers with a pCR or marked response were classified as chemosensitive breast cancer. The remaining 64 breast cancers (53%) were classified as chemoresistant breast cancer. Large tumour size, a lesion without mass effect, and very high intratumoural signal intensity on T2-weighted MR images were significantly associated with chemoresistant breast cancer. Lesions with mass effect and washout enhancement pattern were significantly associated with chemosensitive breast cancer. Areas with very high intratumoural signal intensity on T2-weighted images corresponded pathologically to areas of intratumoural necrosis. Several MR imaging features of breast cancer before NAC can help predict the efficacy of NAC. (orig.)

Life-style and death patterns of the Missouri RLDS church members.

Science.gov (United States)

McEvoy, L; Land, G

1981-12-01

Members of the Reorganized Church of Jesus Christ of Latter-Day Saints (RLDS) are dissuaded from the use of tobacco, alcohol, and hot drinks. A well-balanced diet is also stressed. This study compares the 1972-78 mortality experience of the Missouri RLDS with three other population groups. The findings show Missouri RLDS experiencing age-adjusted death rates which are 22.6 percent lower than rates for Missouri non-RLDs whites; 19.6 per cent lower than the non-RLDS of Independence, Missouri; and 14.4 per cent lower than Utah residents. The RLDS display lower death rates than the two Missouri comparison groups for each of seven selected causes-particularly lung cancer, pneumonia/influenza, and violent deaths. Comparisons between the Missouri RLDS and Utah residents show an inconsistent pattern, with Utah residents having non-significantly lower death rates for lung cancer and ischemic heart disease, but with the Missouri RLDS having significantly lower rates for pneumonia/influenza and violent deaths. These inconsistencies are of interest because 72 per cent of Utah's population belong to the Mormon Church which advocates life-styles similar to the RLDS. If these disparate mortality patterns persist under a more direct comparison between the Missouri RLDS and Utah Mormons, they could provide the opportunity to assess the impact of similar life-styles in separate settings.

Death following the ingestion of detergent: an autopsy case with special regard to the histochemical findings.

Science.gov (United States)

Kawamoto, Osamu; Ishikawa, Takaki; Oritani, Shigeki; Kuramoto, Yuko; Michiue, Tomomi; Maeda, Hitoshi

2013-06-01

We report an autopsy case of death due to accidental ingestion of a liquid laundry detergent with special regard to the histochemical findings. A female inpatient suffering from schizophrenia in a psychiatric institution, was found unconscious lying on the floor of her room, with a container of detergent nearby, and died despite intensive life-support measures. At autopsy, the stomach and duodenum contained whitish translucent foamy viscous fluid, and the mucous membranes, from the esophagus to the duodenum, had diffuse erosions with congestion and edema. There was otherwise no significant pathology other than signs of acute death and hemolysis. Toxicological investigations detected 1-methyl-4-prop-1-en-2-ylcyclohexene (detergent additive) in the gastric contents using headspace-gas chromatography/mass spectrometry, and a nonionic surfactant by a color identification test. Although these substances could not be detected in the blood, body fluid or viscera, histochemical examination using Oil red O demonstrated droplet-like staining in the pulmonary alveoli, suggesting aspiration of detergent, and similar staining in the vasculature of the lung, Kupffer cells of the liver, Bowman capsules of the kidney, and capillaries of the brain, suggesting the systemic effect of ingested/aspirated detergent. These findings were in keeping with death from ingestion of detergent and demonstrated the importance of preventing accidents such as this in healthcare facilities for elderly people.

Marilyn Hacker's Cancer Poems

OpenAIRE

Twiddy, Iain

2012-01-01

Marilyn Hacker's 1994 collection Winter Numbers attempts to come to terms with cancer, including the death of friends from the disease, and Hacker's own mastectomy and chemotherapy. Cancer is problematic for poetry, and for elegy in particular, for a number of conceptual, ethical and mimetic reasons. As it seeks to make progress away from the disease through the patterning of rhyme and meter, metaphor, and the assertion of fertility, cancer poetry finds itself replicating the creatively destr...

Changes in causes of death and risk of cancer in Danish patients with autosomal dominant polycystic kidney didease and end-stage renal disease

DEFF Research Database (Denmark)

Ørskov, Bjarne; Feldt-Rasmussen, Bo Friis; Strandgaard, Svend Valdemar

2012-01-01

Abstract Background. With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31...... December 2008. Methods. Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular......, cerebrovascular, infection, other and unknown. Results. Cardiovascular disease was the major cause of death. A multivariate competing risk model comparing the two 8-year periods, adjusted for age at ESRD, gender and treatment modality, showed that deaths from cardiovascular disease decreased by 35% [hazard ratios...

The Global Burden of Cancer 2013

Science.gov (United States)

2015-01-01

IMPORTANCE Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. OBJECTIVE To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. EVIDENCE REVIEW The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. FINDINGS In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16

Twenty-year Risk of Prostate Cancer Death by Midlife Prostate-specific Antigen and a Panel of Four Kallikrein Markers in a Large Population-based Cohort of Healthy Men.

Science.gov (United States)

Sjoberg, Daniel D; Vickers, Andrew J; Assel, Melissa; Dahlin, Anders; Poon, Bing Ying; Ulmert, David; Lilja, Hans

2018-06-01

Prostate-specific antigen (PSA) screening reduces prostate cancer deaths but leads to harm from overdiagnosis and overtreatment. To determine the long-term risk of prostate cancer mortality using kallikrein blood markers measured at baseline in a large population of healthy men to identify men with low risk for prostate cancer death. Study based on the Malmö Diet and Cancer cohort enrolling 11 506 unscreened men aged 45-73 yr during 1991-1996, providing cryopreserved blood at enrollment and followed without PSA screening to December 31, 2014. We measured four kallikrein markers in the blood of 1223 prostate cancer cases and 3028 controls. Prostate cancer death (n=317) by PSA and a prespecified statistical model based on the levels of four kallikrein markers. Baseline PSA predicted prostate cancer death with a concordance index of 0.86. In men with elevated PSA (≥2.0ng/ml), predictive accuracy was enhanced by the four-kallikrein panel compared with PSA (0.80 vs 0.73; improvement 0.07; 95% confidence interval 0.04, 0.10). Nearly half of men aged 60+ yr with elevated PSA had a four-kallikrein panel score of four-kallikrein panel score of ≥7.5% had a 13% risk of prostate cancer death at 15 yr. A prespecified statistical model based on four kallikrein markers (commercially available as the 4Kscore) reclassified many men with modestly elevated PSA, to have a low long-term risk of prostate cancer death. Men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Men with elevated prostate-specific antigen (PSA) are often referred for prostate biopsy. However, men with elevated PSA but low scores from the four-kallikrein panel can be monitored rather than being subject to biopsy. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.

Science.gov (United States)

Minicozzi, Pamela; Berrino, Franco; Sebastiani, Federica; Falcini, Fabio; Vattiato, Rosa; Cioccoloni, Francesca; Calagreti, Gioia; Fusco, Mario; Vitale, Maria Francesca; Tumino, Rosario; Sigona, Aurora; Budroni, Mario; Cesaraccio, Rosaria; Candela, Giuseppa; Scuderi, Tiziana; Zarcone, Maurizio; Campisi, Ildegarda; Sant, Milena

2013-12-01

We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008. For 1607 Italian women (≥15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (≤84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (≤23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER-PR- cases were also run. Patients often had T1-3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95% confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1-94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Toxicologic Laboratory Findings in Cases Reported with Hanging Death: a Two-Year Retrospective Study in Northeast Iran

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Mohammad Ranjbar

2013-09-01

How to cite this article: Ranjbar R, Liaghat AR, Ranjbar A, Mohabbati H. Toxicologic Laboratory Findings in Cases Reported with Hanging Death: a Two-Year Retrospective Study in Northeast Iran. Asia Pac J Med Toxicol 2013;2:92-5.

Lung cancer screening: Update

International Nuclear Information System (INIS)

Kim, Hyea Young

2015-01-01

Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers

Lung cancer screening: Update

Energy Technology Data Exchange (ETDEWEB)

Kim, Hyea Young [Dept. of Radiology, Center for Lung Cancer, National Cancer Center, Goyang (Korea, Republic of)

2015-09-15

Lung cancer is the leading cause of cancer deaths worldwide as well as in Korea. A recent National Lung Screening Trial in U.S. revealed that low-dose CT (LDCT) screening reduced lung cancer specific mortality by 20% in high risk individuals as compared to chest radiograph screening. Based on this evidence, several expert societies in U.S. and Korean multisociety collaborative committee developed guidelines for recommendation of lung cancer screening using annual LDCT in high risk populations. In most of the societies high risk groups are defined as persons aged 55 to 74 years, who are current smokers with history of smoking of more than 30 packs per year or ex-smokers, who quit smoking up to 15 or more years ago. The benefits of LDCT screening are modestly higher than the harms in high risk individuals. The harms included a high rate of false-positive findings, over-diagnosis and radiation-related deaths. Invasive diagnostic procedure due to false positive findings may lead to complications. LDCT should be performed in qualified hospitals and interpreted by expert radiologists. Recently, the American College of Radiology released the current version of Lung cancer CT screening Reporting and Data Systems. Education and actions to stop smoking must be offered to current smokers.

Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study.

Science.gov (United States)

Feng, Yuan; Zhou, Jihong; Li, Zhanhua; Jiang, Ying; Zhou, Ying

2016-01-01

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines) and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5) induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID) mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.

Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study.

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Yuan Feng

Full Text Available Tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5 induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.

Attributable causes of esophageal cancer incidence and mortality in China.

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Jian-Bing Wang

Full Text Available To estimate the contribution of tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake to esophageal cancer mortality and incidence in China.We calculated the proportion of esophageal cancer attributable to four known modifiable risk factors [population attributable fraction (PAF]. Exposure data was taken from meta-analyses and large-scale national surveys of representative samples of the Chinese population. Data on relative risks were also from meta-analyses and large-scale prospective studies. Esophageal cancer mortality and incidence came from the 3(rd national death cause survey and population-based cancer registries in China. We estimated that 87,065 esophageal cancer deaths (men 67,686; women: 19,379 and 108,206 cases (men: 83,968, women: 24,238 were attributable to tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake in China in 2005. About 17.9% of esophageal cancer deaths among men and 1.9% among women were attributable to tobacco smoking. About 15.2% of esophageal cancer deaths in men and 1.3% in women were caused by alcohol drinking. Low vegetable intake was responsible for 4.3% esophageal cancer deaths in men and 4.1% in women. The fraction of esophageal cancer deaths attributable to low fruit intake was 27.1% in men and 28.0% in women. Overall, 46% of esophageal cancers (51% in men and 33% in women were attributable to these four modifiable risk factors.Tobacco smoking, alcohol drinking, low vegetable intake and low fruit intake were responsible for 46% of esophageal cancer mortality and incidence in China in 2005. These findings provide useful data for developing guidelines for esophageal cancer prevention and control in China.

A primary liver cancer death's survey and risk factors analysis of the workers in China nuclear industry

International Nuclear Information System (INIS)

Bao Shouchen; Chang Xuezhang; Gao Zenglin; Xiong Jinlian; Zhang Xuzong; Zhang Zhongren

1999-07-01

To evaluate primary liver cancer death in the workers of China nuclear industry and to discuss the risk factors probably for making protection and cure measures, the workers of 11 units are surveyed from the time of foundation to the end of 1990 by groups, trades and sex, and the results are analyzed with the relevant physical examinations, the results in laboratory test, and some clinic epidemiological data concerned. The accumulative rough mortality is 19.20 x 10 -5 , standard mortality 10.09 x 10 -5 , the most is at the age of 35 to 54. SMR 1.00 (P > 0.05), RR value in uranium mines is 3.67 (P < 0.01) and others does not increase. The incidence of hepatomegalia and GPT rising are lower than or about 10%, while the incidence of HBsAg is lower than 8%, a middle-levelled infection in the country. And HBsAg incidence in liver cancer cases is 61.6% and chronic hepatitis in liver cancer cases is 53.4%. The liver cancer case increase in the workers in nuclear industry is not found, but significant increase is found in uranium mine workers; whereas there is no evidence that can be attributed to radiation operation, and the death risk may be considered mainly to be related to HBV infection, then chronic hepatitis or environment factors

Cell death triggered by alpha-emitting {sup 213}Bi-immunoconjugates in HSC45-M2 gastric cancer cells is different from apoptotic cell death

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Seidl, Christof; Schroeck, Hedwig; Seidenschwang, Sabine; Beck, Roswitha; Schwaiger, Markus; Senekowitsch-Schmidtke, Reingard [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Schmid, Ernst [National Research Center for Environment and Health, Institute of Radiation Biology, GSF, Neuherberg (Germany); Abend, Michael [German Armed Forces, Institute of Radiobiology, Munich (Germany); Becker, Karl-Friedrich [Technische Universitaet Muenchen, Institute of Pathology, Munich (Germany); National Research Center for Environment and Health, Institute of Pathology, GSF, Neuherberg (Germany); National Research Center for Environment and Health, Institute of Molecular Immunology, GSF, Munich (Germany); Apostolidis, Christos; Nikula, Tuomo K. [European Commission, Institute for Transuranium Elements, Karlsruhe (Germany); Kremmer, Elisabeth [National Research Center for Environment and Health, Institute of Molecular Immunology, GSF, Munich (Germany)

2005-03-01

Radioimmunotherapy with {alpha}-particle-emitting nuclides, such as{sup 213}Bi, is a promising concept for the elimination of small tumour nodules or single disseminated tumour cells. The aim of this study was to investigate cellular damage and the mode of cell death triggered by {sup 213}Bi-immunoconjugates. Human gastric cancer cells (HSC45-M2) expressing d9-E-cadherin were incubated with different levels of activity of {sup 213}Bi-d9MAb targeting d9-E-cadherin and {sup 213}Bi-d8MAb, which does not bind to d9-E-cadherin. Micronucleated (M) cells, abnormal (A) cells and apoptotic (A) [(MAA)] cells were scored microscopically in the MAA assay following fluorescent staining of nuclei and cytoplasm. Chromosomal aberrations were analysed microscopically following Giemsa staining. The effect of z-VAD-fmk, known to inhibit apoptosis, on the prevention of cell death was investigated following treatment of HSC45-M2 cells with sorbitol as well as {sup 213}Bi-d9MAb. Activation of caspase 3 after incubation of HSC45-M2 cells with both sorbitol and {sup 213}Bi-d9MAb was analysed via Western blotting. Following incubation of HSC45-M2 human gastric cancer cells expressing d9-E-cadherin with {sup 213}Bi-d9MAb the number of cells killed increased proportional to the applied activity concentration. Microscopically visible effects of {alpha}-irradiation of HSC45-M2 cells were formation of micronuclei and severe chromosomal aberrations. Preferential induction of these lesions with specific {sup 213}Bi-d9MAb compared with unspecific {sup 213}Bi-d8MAb (not targeting d9-E-cadherin) was not observed if the number of floating, i.e. unbound {sup 213}Bi-immunoconjugates per cell exceeded 2 x 10{sup 4}, most likely due to intense crossfire. In contrast to sorbitol-induced cell death, cell death triggered by {sup 213}Bi-immunoconjugates was independent of caspase 3 activation and could not be inhibited by z-VAD-fmk, known to suppress the apoptotic pathway. {sup 213}Bi-immunoconjugates seem

Impressions That Last: Particularly Negative and Positive Experiences Reported by Parents Five Years after the End of a Child's Successful Cancer Treatment or Death.

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Lisa Ljungman

Full Text Available To describe the experience of parenting a child diagnosed with cancer by examining particularly negative and positive experiences reported by parents of childhood cancer survivors and parents of children lost to cancer.168 parents (88 mothers, 80 fathers participated. Data were collected five years after the end of successful treatment or the child's death. The parents' experiences were identified by open-ended semi-structured questions about particularly negative and positive experiences of the child's cancer. An inductive approach was used in which the manifest verbal content of the answers was analysed using content analysis.The analysis revealed eight categories of negative experience (child late effects; distressing events; healthcare; impaired relationships; long-term psychological consequences; own reactions; surrounding institutions; the fact that the child got cancer and seven categories of positive experience (healthcare; improved relationships; long-term consequences for the child; personal development; support systems; treatment outcome; unexpected joy. The categories were related to past events or to the present situation. The findings indicate variations in experiences between parents of survivors and bereaved parents, and between fathers and mothers, as some experiences were only reported by parents of survivors and some experiences were only reported by mothers.The results highlight the importance of past and present events to parents, and accordingly the long-lasting impact of paediatric cancer on parents. The results also point to the wide range of negative as well as positive experiences involved in parenting a child diagnosed with cancer, and provide a comprehensive understanding of the overall experience for parents of children with cancer. Specifically, the findings give guidance to healthcare providers by illustrating the need to provide healthcare personnel with continuous training in communication skills, offering

Expression of Prostacyclin-Synthase in Human Breast Cancer: Negative Prognostic Factor and Protection against Cell Death In Vitro

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Thomas Klein

2015-01-01

Full Text Available Endogenously formed prostacyclin (PGI2 and synthetic PGI2 analogues have recently been shown to regulate cell survival in various cell lines. To elucidate the significance of PGI2 in human breast cancer, we performed immunohistochemistry to analyze expression of prostacyclin-synthase (PGIS in 248 human breast cancer specimens obtained from surgical pathology files. We examined patients’ 10-year survival retrospectively by sending a questionnaire to their general practitioners and performed univariate analysis to determine whether PGIS expression correlated with patient survival. Lastly, the effects of PGI2 and its analogues on cell death were examined in a human breast cancer cell line (MCF-7 and a human T-cell leukemia cell line (CCRF-CEM. PGIS expression was observed in tumor cells in 48.7% of samples and was associated with a statistically significant reduction in 10-year survival (P=0.038; n=193. Transient transfection of PGIS into MCF-7 cells exposed to sulindac increased cell viability by 50% and exposure to carbaprostacyclin protected against sulindac sulfone induced apoptosis in CCRF-CEM cells. Expression of PGIS is correlated with a reduced patient survival and protects against cell death in vitro, suggesting that PGIS is a potential therapeutic target in breast cancer.

Can we rely on cancer mortality data? Checking the validity of cervical cancer mortality data for Slovenia

International Nuclear Information System (INIS)

Primic Zakelj, M.; Pompe Kirn, V.; Skrlec, F.; Selb, J.

2001-01-01

Background. Valid inference on cervical cancer mortality is very difficult since - on the basis of death certificates - it is not always possible to distinguish between cervix, corpus and unspecified uterine cancer deaths. Our aim was to estimate the extent to which cervical cancer as the official cause of death reflects the true mortality from cervical cancer in Slovenia. Material and methods. The data on 2245 deaths from cervix, corpus uteri, and uterus-unspecified cancers for the period 1985-1999 were linked to the Cancer Registry of Slovenia database from the mortality database of Slovenia. Results. Officially, in the period 1985-1999, there were 878 cervical cancer deaths. The comparison of these causes of death with the cancer sites registered in the Cancer Registry revealed that they include only 87.7% patients with a previous diagnosis of cervical cancer. Of 650 corpus uteri cancer deaths, 17. 1 % of patients were registered to have cervical cancer, and of 717 unspecified uterine cancer deaths, 31.4% were registered. Taking into account the correctly identified cervical cancer cases among cervical cancer deaths and misclassified cervical cancer deaths as corpus uteri and unspecified uterine, the corrected number of deaths would be 1106. Conclusions. When evaluating the impact of cervical cancer mortality from national mortality rates, the stated underestimation should be taken into account. However, this does not hold for some other cancers. (author)

Deliberating death.

Science.gov (United States)

Landes, Scott D

2010-01-01

Utilizing a particular case study of a woman attempting to come to terms with her death, this article explores the difficult metaphors of death present within the Christian tradition. Tracing a Christian understanding of death back to the work of Augustine, the case study is utilized to highlight the difficulties presented by past and present theology embracing ideas of punishment within death. Following the trajectory of the case study, alternative understandings of death present in recent Christian theology and within Native American spirituality are presented in an attempt to find room for a fuller meaning of death post-reconciliation, but premortem.

Cancer mortality in women after repeated fluoroscopic examinations of the chest

International Nuclear Information System (INIS)

Boice, J.D.; Monson, R.R.; Rosenstein, M.

1981-01-01

Among 1,047 women fluoroscopically examined in average of 102 times during pneumothorax therapy for tuberculosis and followed up to 45 years (average . 27 yr), no increase in the total number of cancer deaths occurred when these women were compared to 717 women who received other treatments [relative risk (RR) . 0.8]. However, elevated risks of mortality from stomach cancer (RR . 2.3), rectal cancer (RR . 3.8), breast cancer (RR . 1.2), lung cancer (RR . 1.8), and leukemia (RR . 1.2) were observed, but none was statistically significant and all were based on very small numbers of deaths. These increases were balanced by decreases of genital cancer (RR . 0.2), pancreatic cancer (RR . 0.9), lymphoma (RR . 0.6), and all other cancers (RR . 0.1). Average cumulative absorbed doses were 110 rads for the lungs, 33 rads for the trunk, 13 rads for the active bone marrow, and 7 rads for the stomach. The following upper levels of excess risk could be excluded with 95% confidence: 3.5 deaths/10(6) woman-year (WY)-rad for lung cancer, 4.8 deaths/10(6) WY-rad for lymphoma, and 12 deaths/10(6) WY-rad for leukemia. These findings indicated that the carcinogenic effect of multiple low-dose X-ray exposures was not greater than that currently assumed

ROS-mediated apoptotic cell death in prostate cancer LNCaP cells induced by biosurfactant stabilized CdS quantum dots.

Science.gov (United States)

Singh, Braj R; Singh, Brahma N; Khan, W; Singh, H B; Naqvi, A H

2012-08-01

Cadmium sulfide (CdS) quantum dots (QDs) have raised great attention because of their superior optical properties and wide utilization in biological and biomedical studies. However, little is known about the cell death mechanisms of CdS QDs in human cancer cells. This study was designed to investigate the possible mechanisms of apoptosis induced by biosurfactant stabilized CdS QDs (denoted as "bsCdS QDs") in human prostate cancer LNCaP cells. It was also noteworthy that apoptosis correlated with reactive oxygen species (ROS) production, mitochondrial damage, oxidative stress and chromatin condensation in a dose- and time-dependent manner. Results also showed involvement of caspases, Bcl-2 family proteins, heat shock protein 70, and a cell-cycle checkpoint protein p53 in apoptosis induction by bsCdS QDs in LNCaP cells. Moreover, pro-apoptotic protein Bax was upregulated and the anti-apoptotic proteins, survivin and NF-κB were downregulated in bsCdS QDs exposed cells. Protection of N-acetyl cysteine (NAC) against ROS clearly suggested the implication of ROS in hyper-activation of apoptosis and cell death. It is encouraging to conclude that biologically stabilized CdS QDs bear the potential of its applications in biomedicine, such as tumor therapy specifically by inducing caspase-dependent apoptotic cell death of human prostate cancer LNCaP cells. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Hyperthermia-enhanced TRAIL- and mapatumumab-induced apoptotic death is mediated through mitochondria in human colon cancer cells.

Science.gov (United States)

Song, Xinxin; Kim, Han-Cheon; Kim, Seog-Young; Basse, Per; Park, Bae-Hang; Lee, Byeong-Chel; Lee, Yong J

2012-05-01

Colorectal cancer is the third leading cause of cancer-related mortality in the world; death usually results from uncontrolled metastatic disease. Previously, we developed a novel strategy of TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) in combination with hyperthermia to treat hepatic colorectal metastases. However, previous studies suggest a potential hepatocyte cytotoxicity with TRAIL. Unlike TRAIL, anti-human TRAIL receptor antibody induces apoptosis without hepatocyte toxicity. In this study, we evaluated the anti-tumor efficacy of humanized anti-death receptor 4 (DR4) antibody mapatumumab (Mapa) by comparing it with TRAIL in combination with hyperthermia. TRAIL, which binds to both DR4 and death receptor 5 (DR5), was approximately tenfold more effective than Mapa in inducing apoptosis. However, hyperthermia enhances apoptosis induced by either agent. We observed that the synergistic effect was mediated through elevation of reactive oxygen species, c-Jun N-terminal kinase activation, Bax oligomerization, and translocalization to the mitochondria, loss of mitochondrial membrane potential, release of cytochrome c to cytosol, activation of caspases, and increase in poly(ADP-ribose) polymerase cleavage. We believe that the successful outcome of this study will support the application of Mapa in combination with hyperthermia to colorectal hepatic metastases. Copyright © 2011 Wiley Periodicals, Inc.

Thyroid cancer outcomes in Filipino patients.

Science.gov (United States)

Kus, Lukas H; Shah, Manish; Eski, Spiro; Walfish, Paul G; Freeman, Jeremy L

2010-02-01

To compare the outcomes of patients having thyroid cancer among Filipinos vs non-Filipinos. Retrospective medical record review. High-volume tertiary referral center in Toronto, Ontario, Canada. A total of 499 patients with thyroid cancer (36 Filipino and 463 non-Filipino) treated at Mount Sinai Hospital from January 1, 1984, to August 31, 2003, with a minimum 5-year follow-up period and a minimum 1.0-cm tumor size. Patients were identified from a thyroid cancer database. Data on patient, tumor, and treatment factors were collected along with outcomes. The presence of thyroid cancer recurrence, the rate of death from disease, and the time to recurrence. The 2 groups were similar for sex, age, history of head and neck radiation exposure, family history of thyroid cancer, follow-up time, tumor size, tumor pathologic findings, presence of tumor multifocality, stage of primary disease, type of thyroid surgery, use of postoperative radioactive iodine therapy, and use of external beam radiation therapy. Filipino patients experienced a thyroid cancer recurrence rate of 25% compared with 9.5% for non-Filipino patients (odds ratio, 3.20; 95% confidence interval, 1.23-7.49; P = .004). On multivariate analysis, the increased risk of thyroid cancer recurrence persisted for Filipino patients (odds ratio, 6.99; 95% confidence interval, 2.31-21.07; P Filipino patients and non-Filipino patients regarding the rate of death from disease (5.6% vs 1.9%) and the time to recurrence (52.6 vs 53.1 months). Filipino patients have a significantly higher risk of thyroid cancer recurrence compared with non-Filipino patients. However, no significant difference was noted in the time to recurrence or the rate of death from disease. These findings justify a more aggressive initial management and follow-up regimen for Filipino patients with thyroid cancer.

Awareness of General Practitioners concerning cancer patients’ preferences for place of death: evidence from four European countries.

NARCIS (Netherlands)

Ko, W.; Beccaro, M.; Miccinesi, G.; Casteren, V. van; Donker, G.A.; Onwuteaka-Philipsen, B.; Espi, M.T.M.; Deliens, L.; Costantini, M.; Block, L. van den

2013-01-01

Background: General Practitioners (GPs) are at the first level of contact in many European healthcare systems and they supposedly have a role in supporting cancer patients in achieving their desired place of death. A four-country (Belgium, the Netherlands, Italy and Spain) study was carried out

Awareness of General Practitioners concerning cancer patients' preferences for place of death: Evidence from four European countries

NARCIS (Netherlands)

Ko, W.; Beccaro, M.; Miccinesi, G.; van Casteren, V.; Donker, G.A.; Onwuteaka-Philipsen, B.D.; Espi, M.T.; Deliens, L.; Costantini, M.; Block, L.

2013-01-01

Background: General Practitioners (GPs) are at the first level of contact in many European healthcare systems and they supposedly have a role in supporting cancer patients in achieving their desired place of death. A four-country (Belgium, the Netherlands, Italy and Spain) study was carried out

Patient survival and tumor characteristics associated with CHEK2:p.I157T - findings from the Breast Cancer Association Consortium.

Science.gov (United States)

Muranen, Taru A; Blomqvist, Carl; Dörk, Thilo; Jakubowska, Anna; Heikkilä, Päivi; Fagerholm, Rainer; Greco, Dario; Aittomäki, Kristiina; Bojesen, Stig E; Shah, Mitul; Dunning, Alison M; Rhenius, Valerie; Hall, Per; Czene, Kamila; Brand, Judith S; Darabi, Hatef; Chang-Claude, Jenny; Rudolph, Anja; Nordestgaard, Børge G; Couch, Fergus J; Hart, Steven N; Figueroa, Jonine; García-Closas, Montserrat; Fasching, Peter A; Beckmann, Matthias W; Li, Jingmei; Liu, Jianjun; Andrulis, Irene L; Winqvist, Robert; Pylkäs, Katri; Mannermaa, Arto; Kataja, Vesa; Lindblom, Annika; Margolin, Sara; Lubinski, Jan; Dubrowinskaja, Natalia; Bolla, Manjeet K; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Easton, Douglas F; Pharoah, Paul D P; Schmidt, Marjanka K; Nevanlinna, Heli

2016-10-03

P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers. We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models. Additionally, we explored the p.I157T-associated genomic gene expression profile using data from breast tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO: GSE24450). Differential gene expression analysis was performed using a moderated t test. Functional enrichment was investigated using the DAVID functional annotation tool and gene set enrichment analysis (GSEA). The tumors were classified into molecular subtypes according to the St Gallen 2013 criteria and the PAM50 gene expression signature. P.I157T was not associated with increased risk of early death, breast cancer-associated death or distant metastasis relapse, and there was a significant difference in prognosis associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore, p.I157T was associated with lobular histological type and clinico-pathological markers of good prognosis, such as ER and PR expression, low TP53 expression and low grade. Gene expression analysis suggested luminal A to be the most common subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be significantly

Natriuretic peptide receptor A inhibition suppresses gastric cancer development through reactive oxygen species-mediated G2/M cell cycle arrest and cell death.

Science.gov (United States)

Li, Zheng; Wang, Ji-Wei; Wang, Wei-Zhi; Zhi, Xiao-Fei; Zhang, Qun; Li, Bo-Wen; Wang, Lin-Jun; Xie, Kun-Ling; Tao, Jin-Qiu; Tang, Jie; Wei, Song; Zhu, Yi; Xu, Hao; Zhang, Dian-Cai; Yang, Li; Xu, Ze-Kuan

2016-10-01

Natriuretic peptide receptor A (NPRA), the major receptor for atrial natriuretic peptide (ANP), has been implicated in tumorigenesis; however, the role of ANP-NPRA signaling in the development of gastric cancer remains unclear. Immunohistochemical analyses indicated that NPRA expression was positively associated with gastric tumor size and cancer stage. NPRA inhibition by shRNA induced G2/M cell cycle arrest, cell death, and autophagy in gastric cancer cells, due to accumulation of reactive oxygen species (ROS). Either genetic or pharmacologic inhibition of autophagy led to caspase-dependent cell death. Therefore, autophagy induced by NPRA silencing may represent a cytoprotective mechanism. ROS accumulation activated c-Jun N-terminal kinase (JNK) and AMP-activated protein kinase (AMPK). ROS-mediated activation of JNK inhibited cell proliferation by disturbing cell cycle and decreased cell viability. In addition, AMPK activation promoted autophagy in NPRA-downregulated cancer cells. Overall, our results indicate that the inhibition of NPRA suppresses gastric cancer development and targeting NPRA may represent a promising strategy for the treatment of gastric cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of a Clinical Tool to Predict Home Death of a Discharged Cancer Patient in Japan: a Case-Control Study.

Science.gov (United States)

Fukui, Sakiko; Morita, Tatsuya; Yoshiuchi, Kazuhiro

2017-08-01

The aim of this study was to investigate the predictive value of a clinical tool to predict whether discharged cancer patients die at home, comparing groups of case who died at home and control who died in hospitals or other facilities. We conducted a nationwide case-control study to identify the determinants of home death for a discharged cancer patient. We randomly selected nurses in charge of 2000 home-visit nursing agencies from all 5813 agencies in Japan by referring to the nationwide databases in January 2013. The nurses were asked to report variables of their patients' place of death, patients' and caregivers' clinical statuses, and their preferences for home death. We used logistic regression analysis and developed a clinical tool to accurately predict it and investigated their predictive values. We identified 466 case and 478 control patients. Five predictive variables of home death were obtained: patients' and caregivers' preferences for home death [OR (95% CI) 2.66 (1.99-3.55)], availability of visiting physicians [2.13 (1.67-2.70)], 24-h contact between physicians and nurses [1.68 (1.30-2.18)], caregivers' experiences of deathwatch at home [1.41 (1.13-1.75)], and patients' insights as to their own prognosis [1.23 (1.02-1.50)]. We calculated the scores predicting home death for each variable (range 6-28). When using a cutoff point of 16, home death was predicted with a sensitivity of 0.72 and a specificity of 0.81 with the Harrell's c-statistic of 0.84. This simple clinical tool for healthcare professionals can help predict whether a discharged patient is likely to die at home.

Functionalized magnetic nanowires for chemical and magneto-mechanical induction of cancer cell death

KAUST Repository

Martinez Banderas, Aldo; Aires, Antonio; Teran, Francisco J.; Perez, Jose E.; Cadenas, Jael F.; Alsharif, Nouf; Ravasi, Timothy; Cortajarena, Aitziber L.; Kosel, Jü rgen

2016-01-01

Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX. Internalization was assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal analysis, BSA formulations demonstrated higher internalization and less agglomeration. The functionalized NWs generated a comparable cytotoxic effect in breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by free DOX and non-functionalized NWs formulations. A synergistic cytotoxic effect is obtained when a magnetic field (1 mT, 10 Hz) is applied to cells treated with DOX-functionalized BSA or APTES-coated NWs, (~70% at the highest concentration). In summary, a bimodal method for cancer cell destruction was developed by the conjugation of the magneto-mechanical properties of iron NWs with the effect of DOX producing better results than the individual effects.

Functionalized magnetic nanowires for chemical and magneto-mechanical induction of cancer cell death

KAUST Repository

Martinez Banderas, Aldo Isaac

2016-10-24

Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX. Internalization was assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal analysis, BSA formulations demonstrated higher internalization and less agglomeration. The functionalized NWs generated a comparable cytotoxic effect in breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by free DOX and non-functionalized NWs formulations. A synergistic cytotoxic effect is obtained when a magnetic field (1 mT, 10 Hz) is applied to cells treated with DOX-functionalized BSA or APTES-coated NWs, (~70% at the highest concentration). In summary, a bimodal method for cancer cell destruction was developed by the conjugation of the magneto-mechanical properties of iron NWs with the effect of DOX producing better results than the individual effects.

Functionalized magnetic nanowires for chemical and magneto-mechanical induction of cancer cell death.

Science.gov (United States)

Martínez-Banderas, Aldo Isaac; Aires, Antonio; Teran, Francisco J; Perez, Jose Efrain; Cadenas, Jael F; Alsharif, Nouf; Ravasi, Timothy; Cortajarena, Aitziber L; Kosel, Jürgen

2016-10-24

Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX. Internalization was assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal analysis, BSA formulations demonstrated higher internalization and less agglomeration. The functionalized NWs generated a comparable cytotoxic effect in breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by free DOX and non-functionalized NWs formulations. A synergistic cytotoxic effect is obtained when a magnetic field (1 mT, 10 Hz) is applied to cells treated with DOX-functionalized BSA or APTES-coated NWs, (~70% at the highest concentration). In summary, a bimodal method for cancer cell destruction was developed by the conjugation of the magneto-mechanical properties of iron NWs with the effect of DOX producing better results than the individual effects.

The relationship of radiological findings and pathological types of primary lung cancer

International Nuclear Information System (INIS)

Kang, Hye Jung; Baik, Dae Il; Han, Chang Yul; Park, Soo Sung

1982-01-01

The present study was intended to define the relationship of radiological findings and pathological types of primary lung cancer. The 85 cases was selected after confirmation of the cell types by bronchoscopic biopsy, cervical lymph node or thoracotomy biopsy and lung resection. Results of the study were presented below. 1. Primary lung cancer is frequently developed after 4th decade and males were affected more frequently than females with ratio of 2 to 1. 2. The frequencies of pathologic cell types of lung cancer were presented as follows. Squamous cell carcinoma 40% Adenocarcinoma 25% Undifferential cell carcinoma 30% Alveolar cell carcinoma 5% 3. The findings of plain chest radiography were presented as follows. In squamous cell carcinoma. hilar enlargement or hilar mass is the most frequent findings (53%) with atelectasis (26%) or obstructive pneumonitis (26%). In adenocarcinoma, pleural effusion is accompanied about half of cases (53%). In undifferential cell carcinoma, hilar mass with mediastinal widening and pleural effusion is frequent finding

Akebia saponin PA induces autophagic and apoptotic cell death in AGS human gastric cancer cells.

Science.gov (United States)

Xu, Mei-Ying; Lee, Dong Hwa; Joo, Eun Ji; Son, Kun Ho; Kim, Yeong Shik

2013-09-01

In this study, we investigated the anticancer mechanism of akebia saponin PA (AS), a natural product isolated from Dipsacus asperoides in human gastric cancer cell lines. It was shown that AS-induced cell death is caused by autophagy and apoptosis in AGS cells. The apoptosis-inducing effect of AS was characterized by annexin V/propidium (PI) staining, increase of sub-G1 phase and caspase-3 activation, while the autophagy-inducing effect was indicated by the formation of cytoplasmic vacuoles and microtubule-associated protein 1 light chain-3 II (LC3-II) conversion. The autophagy inhibitor bafilomycin A1 (BaF1) decreased AS-induced cell death and caspase-3 activation, but caspase-3 inhibitor Ac-DEVD-CHO did not affect LC3-II accumulation or AS-induced cell viability, suggesting that AS induces autophagic cell death and autophagy contributes to caspase-3-dependent apoptosis. Furthermore, AS activated p38/c-Jun N-terminal kinase (JNK), which could be inhibited by BaF1, and caspase-3 activation was attenuated by both SB202190 and SP600125, indicating that AS-induced autophagy promotes mitogen-activated protein kinases (MAPKs)-mediated apoptosis. Taken together, these results demonstrate that AS induces autophagic and apoptotic cell death and autophagy plays the main role in akebia saponin PA-induced cell death. Copyright © 2013 Elsevier Ltd. All rights reserved.