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Sample records for cancer death rate

  1. Declining death rates reflect progress against cancer.

    Directory of Open Access Journals (Sweden)

    Ahmedin Jemal

    Full Text Available BACKGROUND: The success of the "war on cancer" initiated in 1971 continues to be debated, with trends in cancer mortality variably presented as evidence of progress or failure. We examined temporal trends in death rates from all-cancer and the 19 most common cancers in the United States from 1970-2006. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed trends in age-standardized death rates (per 100,000 for all cancers combined, the four most common cancers, and 15 other sites from 1970-2006 in the United States using joinpoint regression model. The age-standardized death rate for all-cancers combined in men increased from 249.3 in 1970 to 279.8 in 1990, and then decreased to 221.1 in 2006, yielding a net decline of 21% and 11% from the 1990 and 1970 rates, respectively. Similarly, the all-cancer death rate in women increased from 163.0 in 1970 to 175.3 in 1991 and then decreased to 153.7 in 2006, a net decline of 12% and 6% from the 1991 and 1970 rates, respectively. These decreases since 1990/91 translate to preventing of 561,400 cancer deaths in men and 205,700 deaths in women. The decrease in death rates from all-cancers involved all ages and racial/ethnic groups. Death rates decreased for 15 of the 19 cancer sites, including the four major cancers, with lung, colorectum and prostate cancers in men and breast and colorectum cancers in women. CONCLUSIONS/SIGNIFICANCE: Progress in reducing cancer death rates is evident whether measured against baseline rates in 1970 or in 1990. The downturn in cancer death rates since 1990 result mostly from reductions in tobacco use, increased screening allowing early detection of several cancers, and modest to large improvements in treatment for specific cancers. Continued and increased investment in cancer prevention and control, access to high quality health care, and research could accelerate this progress.

  2. Lung cancer death rates fall, helping drive decrease in overall cancer death rates

    Science.gov (United States)

    The Annual Report to the Nation on the Status of Cancer, covering the period 1975–2010, showed death rates for lung cancer, which accounts for more than one in four cancer deaths, dropping at a faster pace than in previous years.

  3. Breast Cancer Death Rates Down 34% Since 1990

    Science.gov (United States)

    ... Text Size News » Filed under: Breast Cancer Report: Breast Cancer Death Rates Down 34% Since 1990 Article date: ... American Cancer Society finds that death rates from breast cancer in the United States have dropped 34% since ...

  4. U.S. congressional district cancer death rates

    Directory of Open Access Journals (Sweden)

    Pickle Linda W

    2006-06-01

    Full Text Available Abstract Background Geographic patterns of cancer death rates in the U.S. have customarily been presented by county or aggregated into state economic or health service areas. Herein, we present the geographic patterns of cancer death rates in the U.S. by congressional district. Many congressional districts do not follow state or county boundaries. However, counties are the smallest geographical units for which death rates are available. Thus, a method based on the hierarchical relationship of census geographic units was developed to estimate age-adjusted death rates for congressional districts using data obtained at county level. These rates may be useful in communicating to legislators and policy makers about the cancer burden and potential impact of cancer control in their jurisdictions. Results Mortality data were obtained from the National Center for Health Statistics (NCHS for 1990–2001 for 50 states, the District of Columbia, and all counties. We computed annual average age-adjusted death rates for all cancer sites combined, the four major cancers (lung and bronchus, prostate, female breast, and colorectal cancer and cervical cancer. Cancer death rates varied widely across congressional districts for all cancer sites combined, for the four major cancers, and for cervical cancer. When examined at the national level, broad patterns of mortality by sex, race and region were generally similar with those previously observed based on county and state economic area. Conclusion We developed a method to generate cancer death rates by congressional district using county-level mortality data. Characterizing the cancer burden by congressional district may be useful in promoting cancer control and prevention programs, and persuading legislators to enact new cancer control programs and/or strengthening existing ones. The method can be applied to state legislative districts and other analyses that involve data aggregation from different geographic

  5. Report to the Nation shows cancer death rates dropping

    Science.gov (United States)

    The Annual Report to the Nation on the Status of Cancer, 1975–2009, shows that overall cancer death rates continued to decline in the United States among both men and women, among all major racial and ethnic groups, and for all of the most common cancer s

  6. Rates of death from lung cancer for Canadian men.

    OpenAIRE

    Irwin, A. C.

    1986-01-01

    According to a recent study the rates of death from lung cancer for white men in the United States began to level off in the late 1970s and decreased between 1982 and 1983. The author reviewed data on death from lung cancer among Canadian men and found that there was an increase of 34% in the adjusted rates between 1971 and 1984. While there was some decrease in the rate of increase among men under the age of 55 years, the rates for men aged 55 or older continued to increase.

  7. Gallbladder Cancer Incidence and Death Rates

    Science.gov (United States)

    ... they can find better ways to prevent it. Risk factors for gallbladder cancer may include— A personal or family history of gallstones. Older age. Being female. Having an American Indian, Alaska Native, or black ...

  8. 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.

  9. Data study of death rate and cancer incidence among Thule workers, 2005

    International Nuclear Information System (INIS)

    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)

  10. 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)

  11. Glutathione in Cancer Cell Death

    International Nuclear Information System (INIS)

    Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy

  12. Glutathione in Cancer Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, Angel L. [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain); Mena, Salvador [Green Molecular SL, Pol. Ind. La Coma-Parc Cientific, 46190 Paterna, Valencia (Spain); Estrela, Jose M., E-mail: jose.m.estrela@uv.es [Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 17 Av. Blasco Ibanez, 46010 Valencia (Spain)

    2011-03-11

    Glutathione (L-γ-glutamyl-L-cysteinyl-glycine; GSH) in cancer cells is particularly relevant in the regulation of carcinogenic mechanisms; sensitivity against cytotoxic drugs, ionizing radiations, and some cytokines; DNA synthesis; and cell proliferation and death. The intracellular thiol redox state (controlled by GSH) is one of the endogenous effectors involved in regulating the mitochondrial permeability transition pore complex and, in consequence, thiol oxidation can be a causal factor in the mitochondrion-based mechanism that leads to cell death. Nevertheless GSH depletion is a common feature not only of apoptosis but also of other types of cell death. Indeed rates of GSH synthesis and fluxes regulate its levels in cellular compartments, and potentially influence switches among different mechanisms of death. How changes in gene expression, post-translational modifications of proteins, and signaling cascades are implicated will be discussed. Furthermore, this review will finally analyze whether GSH depletion may facilitate cancer cell death under in vivo conditions, and how this can be applied to cancer therapy.

  13. Reduction of death rate due to acute myocardial infarction in subjects with cancers through systemic restoration of impaired nitric oxide.

    Directory of Open Access Journals (Sweden)

    Rajeshwary Ghosh

    Full Text Available INTRODUCTION: Excessive aggregation of platelets at the site of plaque rupture on the coronary artery led to the formation of thrombus which is reported to precipitate acute myocardial infarction (AMI. Nitric oxide (NO has been reported to inhibit platelet aggregation and induce thrombolysis through the in situ formation of plasmin. As the plasma NO level in AMI patients from two different ethnic groups was reduced to 0 µM (median compared to 4.0 µM (median in normal controls, the effect of restoration of the NO level to normal ranges on the rate of death due to AMI was determined. METHODS AND RESULTS: The restoration of plasma NO level was achieved by a sticking small cotton pad (10×25 mm containing 0.28 mmol sodium nitroprusside (SNP in 0.9% NaCl to the abdominal skin of the participants using non-toxic adhesive tape which was reported to normalize the plasma NO level. The participants (8,283 were volunteers in an independent study who had different kinds of cancers and did not wish to use any conventional therapy for their condition but opted to receive SNP "pad" for their condition for 3 years. The use of SNP "pad" which normalized (≈4.0 µM the plasma NO level that in consequence reduced the death rate due to AMI, among the participants, was found to be significantly reduced compared to the death due to AMI in normal population. CONCLUSION: Our data suggested that the use of SNP "pad" significantly reduced the death due to AMI. TRIAL REGISTRATION: www.ctri.nic.in CTRI/2013/12/004236.

  14. Prostate-specific antigen (PSA) rate of decline post external beam radiotherapy predicts prostate cancer death

    International Nuclear Information System (INIS)

    Background and purpose: To assess the association between PSA velocity (PSAV) in the first 24 months after external beam radiotherapy (EBRT) and prostate cancer-specific mortality (PCSM) and all cause mortality. Materials and methods: All eligible patients in the South Australian (SA) Prostate Cancer Clinical Outcomes registry were followed. 848 Patients treated by definitive EBRT with more than one PSA recorded in the two year post-treatment were included. We calculated PSAV by linear regression. Results: The mean number of PSA measurements in the 2 year period was 4.4 (SD1.9). The median PSAVs across quartiles (Q1–Q4) were −4.17, −1.29, −0.38 and 0.20 ng/ml/yr. In multivariable analysis, a U-shaped relationship was seen between PSAV and PCSM with Q1–Q4 hazard ratios (HR) being 3.82 (1.46–10.00), 3.07 (1.10–8.58), 1, 5.15 (1.99–13.30) respectively. HR for all cause mortality in a similar model were 1.79 (1.07–2.98), 1.55 (0.93–2.59), 1.00 and 1.74 (1.04–2.90) for Q1 to Q4 respectively. A rapid PSA decline in the first year was a strong predictor of PCSM. However, in the second year PSA increase was positively associated with PCSM. Conclusion: A rapid decline in PSA in the first year following EBRT is positively associated with PCSM. This may be a useful early indicator of the need for additional therapies

  15. Death Rates among Detained Immigrants in the United States

    Directory of Open Access Journals (Sweden)

    Megan Granski

    2015-11-01

    Full Text Available The United States system of immigrant detention centers has been the subject of considerable scrutiny with respect to health care of detainees. We sought to characterize the rates and types of deaths that have occurred within this system between the years 2003–2015. We analyzed a file of detainee deaths released by the U.S. Department of Homeland Security as part of a freedom of information request. Between 2003 and 2015, 150 deaths were recorded. During this time period, the annual rate of death among detainees dropped dramatically, whether measured by annual admissions or by person years of exposure. The most common causes of death were cardiovascular, cancer and suicide. More research is needed to adequately account for the contributors to these declining rates of death in immigration detention settings.

  16. Death Rates among Detained Immigrants in the United States.

    Science.gov (United States)

    Granski, Megan; Keller, Allen; Venters, Homer

    2015-11-01

    The United States system of immigrant detention centers has been the subject of considerable scrutiny with respect to health care of detainees. We sought to characterize the rates and types of deaths that have occurred within this system between the years 2003-2015. We analyzed a file of detainee deaths released by the U.S. Department of Homeland Security as part of a freedom of information request. Between 2003 and 2015, 150 deaths were recorded. During this time period, the annual rate of death among detainees dropped dramatically, whether measured by annual admissions or by person years of exposure. The most common causes of death were cardiovascular, cancer and suicide. More research is needed to adequately account for the contributors to these declining rates of death in immigration detention settings. PMID:26569284

  17. Heart Disease Death Rates in Low Versus High Land Elevation Counties in the U.S

    OpenAIRE

    Hart, John

    2015-01-01

    Previous research on land elevation and cancer death rates in the U.S. revealed lower cancer death rates in higher elevations. The present study further tests the possible effect of land elevation on a diffident health outcome, namely, heart disease death rates. U.S. counties not overlapping in their land elevations according to their lowest and highest elevation points were identified. Using an ecological design, heart disease death rates for two races (black and white) corresponding to lowe...

  18. Late deaths after treatment for childhood cancer.

    OpenAIRE

    Hawkins, M M; Kingston, J. E.; Kinnier Wilson, L. M.

    1990-01-01

    An investigation of 749 deaths occurring among 4082 patients surviving at least five years after the diagnosis of childhood cancer in Britain before 1971 has been undertaken. Of the 738 with sufficient information the numbers of deaths attributable to the following causes were: recurrent tumour, 550 (74%), a second primary tumour, 61 (8%), a medical condition related to treatment of the tumour, 49 (7%), an traumatic death unrelated to the tumour or its treatment, 34 (5%), finally, any other c...

  19. Liver cancer mortality rate model in Thailand

    Science.gov (United States)

    Sriwattanapongse, Wattanavadee; Prasitwattanaseree, Sukon

    2013-09-01

    Liver Cancer has been a leading cause of death in Thailand. The purpose of this study was to model and forecast liver cancer mortality rate in Thailand using death certificate reports. A retrospective analysis of the liver cancer mortality rate was conducted. Numbering of 123,280 liver cancer causes of death cases were obtained from the national vital registration database for the 10-year period from 2000 to 2009, provided by the Ministry of Interior and coded as cause-of-death using ICD-10 by the Ministry of Public Health. Multivariate regression model was used for modeling and forecasting age-specific liver cancer mortality rates in Thailand. Liver cancer mortality increased with increasing age for each sex and was also higher in the North East provinces. The trends of liver cancer mortality remained stable in most age groups with increases during ten-year period (2000 to 2009) in the Northern and Southern. Liver cancer mortality was higher in males and increase with increasing age. There is need of liver cancer control measures to remain on a sustained and long-term basis for the high liver cancer burden rate of Thailand.

  20. Breast Cancer Rates by State

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Breast Cancer Rates by State Language: English Español (Spanish) Recommend ... from breast cancer each year. Rates of Getting Breast Cancer by State The number of people who get ...

  1. ANOVA like analysis of cancer death age

    Science.gov (United States)

    Areia, Aníbal; Mexia, João T.

    2016-06-01

    We use ANOVA to study the influence of year, sex, country and location on the average cancer death age. The data used was from the World Health Organization (WHO) files for 1999, 2003, 2007 and 2011. The locations considered were: kidney, leukaemia, melanoma of skin and oesophagus and the countries: Portugal, Norway, Greece and Romania.

  2. 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

  3. Death Concerns among Individuals Newly Diagnosed with Lung Cancer

    Science.gov (United States)

    Lehto, Rebecca; Therrien, Barbara

    2010-01-01

    Confronting the reality of death is an important challenge for individuals facing life-threatening illness such as lung cancer, the leading cause of cancer death. Few studies, however, document the nature of death-related concerns in individuals newly diagnosed with lung cancer. The aims of this exploratory study were to examine unsolicited…

  4. Reducing the Teen Death Rate. KIDS COUNT Indicator Brief

    Science.gov (United States)

    Shore, Rima; Shore, Barbara

    2009-01-01

    Life continues to hold considerable risk for adolescents in the United States. In 2006, the teen death rate stood at 64 deaths per 100,000 teens (13,739 teens) (KIDS COUNT Data Center, 2009). Although it has declined by 4 percent since 2000, the rate of teen death in this country remains substantially higher than in many peer nations, based…

  5. Lung Cancer Rates by State

    Science.gov (United States)

    ... HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by State Language: English Español (Spanish) Recommend ... incidence data are currently available. Rates of Getting Lung Cancer by State The number of people who get ...

  6. Ovarian Cancer Rates by State

    Science.gov (United States)

    ... HPV-Associated Lung Prostate Skin Uterine Cancer Home Ovarian Cancer Rates by State Language: English Español (Spanish) Recommend ... for which statistics are available. Rates of Getting Ovarian Cancer by State The number of women who get ...

  7. Estimation of cancer deaths in Korea for the upcoming years.

    OpenAIRE

    Bae, Jong-Myon; Jung, Kyu-Won; Won, Young-Joo

    2002-01-01

    Since the cancer has been the leading cause of deaths in Korea, estimation of the cancer deaths for the upcoming years in the population using the vital statistics is considered to be necessary. The aim of this study was to estimate the number and trends of cancer deaths in Korea. The expected numbers of cancer deaths were calculated by a time series model fitting the actual numbers of cancer deaths for each of the years 1983 through 2000 reported by Korea National Statistical Office. The opt...

  8. Regulation of cell death in cancer - possible implications for immunotherapy

    OpenAIRE

    Simone eFulda

    2013-01-01

    Since most anticancer therapies including immunotherapy trigger programmed cell death in cancer cells, defective cell death programs can lead to treatment resistance and tumor immune escape. Therefore, evasion of programmed cell death may provide one possible explanation as to why cancer immunotherapy has so far only shown modest clinical benefits for children with cancer. A better understanding of the molecular mechanisms that regulate sensitivity and resistance to programmed cell death is e...

  9. Long-term recurrence and death rates after acute pancreatitis

    DEFF Research Database (Denmark)

    Lund, Helle; Tønnesen, Hanne; Tønnesen, Maja Hanne;

    2006-01-01

    The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death.......The aim of this study was to compare long-term recurrence and death rates after a first episode of acute pancreatitis in patients with and without gallstones. Additionally, it was of interest to find out if there were factors predictive of readmission or death....

  10. Exchange-Driven Growth with Birth Rate Less Than Death

    Institute of Scientific and Technical Information of China (English)

    LIN Zhen-Quan; KE Jian-Hong; YE Gao-Xiang

    2005-01-01

    We further study the kinetic behavior of the exchange-driven growth with birth and death for the case of birth rate kernel being less than that of death based on the mean-field theory. The symmetric exchange rate kernel is K(k,j) = K'(k,j) = Ikjv, and the birth and death rates are proportional to the aggregate's size. The long time asymptotic behavior of the aggregate size distribution ak(t) is found to obey a much unusual scaling law with an exponentially growing scaling function φ(x) = exp(x).

  11. The influence of death-certificate errors on cancer mortality trends

    International Nuclear Information System (INIS)

    Over the past few years, several reports have suggested a recent increase in cancer mortality based on death-certificate diagnoses. To explore the effect of death-certificate errors on temporal trends in cancer mortality rates, we analyzed the data from the Atomic Bomb Casualty Commission/Radiation Effects Research Foundation's autopsy program in Hiroshima and Nagasaki. This series includes 5886 autopsies conducted between 1961 and 1987. Our analyses were focused on lymphoma, cancer of the breast, neoplasms of the brain, multiple myeloma, and melanoma (172 cases, total) because of concern over reports of their increased mortality. These 172 autopsy cases were referred to as Cancers of Interest. A significant increase in detection rates was observed for these Cancers of Interest primarily due to a large rise in mortality between 1976 and 1987. For the remaining cancers excluding stomach and lung (defined as Other), the pattern was similar to that seen for Cancers of Interest, but the fluctuation over time was not statistically significant. Confirmation rates generally increased with time except for Cancers of Interest. As a measure of bias in mortality rates due to death-certification errors and as a method to quantify under- or overestimation of death-certificate-based mortality rates,an adjustment factor (confirmation rate divided by detection rate) was calculated. The higher the adjustment factor, the greater the need to compensate for underreporting. For Cancers of Interest the adjustment factor decreased dramatically over time, but it did not change significantly for Other cancers. When the adjustment factors for Cancers of Interest and Other were compared, a statistically significant difference was found. For Cancers of Interest, a significant interaction between type of cancer and period was seen. Our findings indicate that considerable care must be shown when interpreting temporal trends in cancer vital statistics. (author)

  12. Global Recession May Have Contributed to Cancer Deaths

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159060.html Global Recession May Have Contributed to Cancer Deaths Health- ... THURSDAY, May 26, 2016 (HealthDay News) -- The 2008 global economic crisis has been linked to a sharp ...

  13. Global Recession May Have Contributed to Cancer Deaths

    Science.gov (United States)

    ... nlm.nih.gov/medlineplus/news/fullstory_159060.html Global Recession May Have Contributed to Cancer Deaths Health- ... THURSDAY, May 26, 2016 (HealthDay News) -- The 2008 global economic crisis has been linked to a sharp ...

  14. 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.

  15. Nerve Growth Factor in Cancer Cell Death and Survival

    International Nuclear Information System (INIS)

    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 p75NTR, a member of the death receptor superfamily. Depending on the tumor origin, pro-survival signaling can be mediated by TrkA receptors or by p75NTR. For example, in breast cancer the aberrant expression of nerve growth factor stimulates proliferative signaling through TrkA and pro-survival signaling through p75NTR. This latter signaling through p75NTR promotes increased resistance to the induction of cell death by chemotherapeutic treatments. In contrast, in prostate cells the p75NTR 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

  16. BIRTH AND DEATH RATES, NATIONAL POPULATION FORECAST AND POPULATION POLICIES

    Directory of Open Access Journals (Sweden)

    K Merat

    1971-07-01

    Full Text Available This study is analyses of national population estimates and aims for the next 20 to 50 years. Calculations are based on the population of 32 million in 1973 with the relative growth rate of 32 in 1000 and death rate of 16 in 1000.Considering various aims, reduction in the growth rate, birth rate and populations in the future years have been calculated. The results showed the need for extensive efforts in reduction of fertility in order to reach zero growth rate in 50 years (2023.

  17. Lung Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of people getting lung cancer or dying from lung cancer varies by race ...

  18. Prostate Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... HPV-Associated Lung Ovarian Skin Uterine Cancer Home Prostate Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of men getting prostate cancer or dying from prostate cancer varies by race ...

  19. Cervical Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Cervical Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of women getting cervical cancer or dying from cervical cancer varies by race ...

  20. Ovarian Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... HPV-Associated Lung Prostate Skin Uterine Cancer Home Ovarian Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of women getting ovarian cancer or dying from ovarian cancer varies by race ...

  1. Colorectal Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Colorectal Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of people getting colorectal cancer or dying from colorectal cancer varies by race ...

  2. Tempo Effects in Different Calculation Types of Period Death Rates

    Directory of Open Access Journals (Sweden)

    Christian Wegner

    2010-01-01

    Full Text Available The question as to whether or not tempo effects distort the measurement of period mortality is controversial in recent demographic research. Only few publications, however, illustrate the underlying phenomenon of tempo effects, namely that the period death rate may increase although the mortality of all cohorts living during the analyzed period has fallen. Moreover, related literature only focuses on one of three methods to derive the age-specific death rate. This article primarily deals with the questions whether other methods of age-specific death rate are also affected by tempo effects in the logic of Bongaarts and Feeney and whether the tempo effect can be minimised solely by applying a specific method. The results demonstrate that all types of death rates are influenced by tempo effects and that different methods do not eliminate the influence of tempo effects. Nevertheless, it is necessary to distinguish between two types of tempo effects, which can be revealed in theoretical as well as empirical perspective.

  3. 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.

  4. Rate of death of hypoxic cells in multicell spheroids

    International Nuclear Information System (INIS)

    The rate of death of hypoxic cells was measured in multicell spheroids, which are considered to model in vitro the microenvironments surrounding such cells within solid tumors. Two types of experiments were performed: (1) All of the cells in spheroids were made hypoxic (less than 100 ppM O2) and the total number of viable cells was determined by clonogenic assay at later times up to 7 days. The rate of death of cells appeared biphasic. At least 15% of the cells died within the first 6 hr. The rate of development of histological changes in the spheroids suggested that the innermost cells were most sensitive. The more peripheral layers of cells died much more slowly so that there was still about 5% survival and a significant number of histologically normal cells at 6 days. Changes in the glucose concentration in the medium (from one-third to three times normal) during exposure to hypoxia had little effect on the survival time of these outer cells. (2) The cells in the inner half of spheroids grown in 20% O2 were made hypoxic by equilibrating the growth medium with 5% O2, and the number of resistant hypoxic cells at different times later was determined after a radiation dose of 3500 rad. The number of surviving clonogenic cells after this dose of radiation decreased with a half-time for cell death of 3 hr. These results indicate that the rate of death of hypoxic cells in the central regions of spheroids is much more rapid than has been reported for monolayer cultures, although the resistance of the outer cells is similar to or greater than monolayers. Since spheroids may model the necrosis and other microenvironments near chronically hypoxic cells in tumors, the relatively rapid rate of death of hypoxic cells demonstrated here must be considered in evaluating their contribution to the size of the radiation-resistant hypoxic fraction and possible mechanisms which might contribute to the phenomenon of reoxygenation

  5. Scared witless about death--ovarian cancer narratives compared.

    Science.gov (United States)

    van Duin, Isabella A J; Kaptein, Ad A

    2013-12-01

    Fifty years ago, doctors did not tell their patients they had cancer. Improved patient-physician communication, feminization of the medical profession and increased patient empowerment may have improved matters. However, death is still a subject many doctors find difficult to deal with. We explore this issue in the context of medical humanities. In order to examine the different strategies in coping with illness and death, we compared illness perceptions in a literary text, W;t by Margaret Edson, about a woman who dies of ovarian cancer, with a personal narrative of a patient with ovarian cancer. Although there are many differences between the two patients in historical and cultural background, similarities were found in the way they cope with illness and death anxiety. Insight into illness perceptions and coping strategies of patients with cancer is important for raising awareness in clinicians, leading to improved understanding and better treatment of patients. PMID:23852816

  6. NCHS - Age-adjusted Death Rates for the Top 10 Leading Causes of Death: United States, 2013

    Data.gov (United States)

    U.S. Department of Health & Human Services — Age-adjusted death rates for the top 10 leading causes of death in the United States, including mortality patterns from 1999 through 2013, and by state of residence...

  7. Predicting death from surgery for lung cancer

    DEFF Research Database (Denmark)

    O'Dowd, Emma L; Lüchtenborg, Margreet; Baldwin, David R;

    2016-01-01

    OBJECTIVES: Current British guidelines advocate the use of risk prediction scores such as Thoracoscore to estimate mortality prior to radical surgery for non-small cell lung cancer (NSCLC). A recent publication used the National Lung Cancer Audit (NLCA) to produce a score to predict 90day mortality...... (NLCA score). The aim of this study is to validate the NLCA score, and compare its performance with Thoracoscore. MATERIALS AND METHODS: We performed an internal validation using 2858 surgical patients from NLCA and an external validation using 3191 surgical patients from the Danish Lung Cancer Registry...... procedure type, age and performance status. CONCLUSIONS: Neither score performs well enough to be advocated for individual risk stratification prior to lung cancer surgery. It may be that additional physiological parameters are required; however this is a further project. In the interim we propose the use...

  8. Colorectal Cancer Stem Cells and Cell Death

    International Nuclear Information System (INIS)

    Nowadays it is reported that, similarly to other solid tumors, colorectal cancer is sustained by a rare subset of cancer stem–like cells (CSCs), which survive conventional anticancer treatments, thanks to efficient mechanisms allowing escape from apoptosis, triggering tumor recurrence. To improve patient outcomes, conventional anticancer therapies have to be replaced with specific approaches targeting CSCs. In this review we provide strong support that BMP4 is an innovative therapeutic approach to prevent colon cancer growth increasing differentiation markers expression and apoptosis. Recent data suggest that in colorectal CSCs, protection from apoptosis is achieved by interleukin-4 (IL-4) autocrine production through upregulation of antiapoptotic mediators, including survivin. Consequently, IL-4 neutralization could deregulate survivin expression and localization inducing chemosensitivity of the colon CSCs pool

  9. Rates and Correlates of Undetermined Deaths among African Americans: Results from the National Violent Death Reporting System

    Science.gov (United States)

    Huguet, Nathalie; Kaplan, Mark S.; McFarland, Bentson H.

    2012-01-01

    Little is known about the factors associated with undetermined death classifications among African Americans. In this study, the rates of undetermined deaths were assessed, the prevalence of missing information was estimated, and whether the circumstances preceding death differ by race were examined. Data were derived from the 2005-2008 National…

  10. Death rate of massive stars at redshift ~0.3

    CERN Document Server

    Cappellaro, E; Altavilla, G; Botticella, M T; Benetti, S; Clocchiatti, A; Danziger, J I; Mazzali, P A; Pastorello, A; Patat, F; Salvo, M; Turatto, M; Valenti, S

    2004-01-01

    We report the first result of a supernova search program designed to measure the evolution of the supernova rate with redshift. To make the comparison with local rates more significant we copied, as much as possible, the same computation recepies as for the measurements of local rates. Moreover, we exploited the multicolor images and the photometric redshift technique to characterize the galaxy sample and accurately estimate the detection efficiency. Combining our data with the recently published meaurements of the SN Ia rate at different redshifts, we derived the first, direct measurement of the core collapse supernova rate at z = 0.26 as r_cc = 1.45 [+0.55, -0.45] h^2 SNu [h=H_0/75]. This is a factor three larger than the local estimate. The increase for a look back time of "only" 2.8 Gyr is more rapid than predicted by most of the published models of the SN rate evolution. Core-collapse SN rates measure the death rate of massive star and, because of the short time scale of evolution, can be translated in a...

  11. Skin Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Skin Cancer Note: Javascript is disabled or is not supported ... HPV-Associated Lung Ovarian Prostate Uterine Cancer Home Skin Cancer Rates by Race and Ethnicity Language: English Español ( ...

  12. Characteristics of Sudden Unexpected Cancer Deaths Investigated by Medical Examiners in Tokyo, Japan (2009)

    OpenAIRE

    ,

    2014-01-01

    Background Annually, about 400 cases of sudden unexpected death are attributed to cancer in Tokyo, Japan. These individuals may have been undiagnosed, or their medical conditions may not have been carefully evaluated before death. We examined medical consultations, cancer diagnoses, and economic status of all cancer deaths investigated by medical examiners in 2009. Methods Among cases handled by the Tokyo Medical Examiner’s Office in 2009 (N = 12 493), records for all cases of cancer death (n...

  13. Higher parity associated with higher risk of death from gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Chih-Ching Chang; Chih-Cheng Chen; Hui-Fen Chiu; Chun-Yuh Yang

    2011-01-01

    AIM: To examine the association between parity and gastric cancer (the cases are almost all premenopausal women) risk in a cohort of young parous women.METHODS: The study cohort consisted of all women with a record of a first and singleton childbirth in the Birth Register between 1978 and 1987. We tracked each woman from the time of her first childbirth to December 31, 2008. Their vital status was ascertained by linking records to the computerized mortality database.Cox proportional hazard regression models were used to estimate hazard ratios of death from gastric cancer associated with parity.RESULTS: There were 1090 gastric cancer deaths (85.87% of them were premenopausal) during 33 686 828 person-years of follow-up. The mortality rate of gastric cancer was 3.24 cases per 100 000 person-years. A trend of increasing risk of gastric cancer was seen with increasing parity. The adjusted hazard ratio was 1.24 [confidence interval (95% CI): 1.02-1.50] for women who had borne two to three children, and 1.32 (95% CI: 1.01-1.72) for women with four or more births, when compared with women who had given birth to only one child.CONCLUSION: These results suggest that higher parity may increase the risk of death from gastric cancer among premenopausal women.

  14. Education, survival, and avoidable deaths in Lithuanian cancer patients, 2001-2009.

    Science.gov (United States)

    Smailyte, Giedre; Jasilionis, Domantas; Vincerzevskiene, Ieva; Shkolnikov, Vladimir M

    2016-07-01

    Background Our aim in this study is to provide a systematic assessment of the site-specific cancer survival rates of patients with different educational levels, using population-based census-linked registry data covering the entire population of Lithuania. Material and methods The study is based on the linkage between all records of the 2001 population census and all records from Lithuanian Cancer Registry (cancer incidence) and Statistics Lithuania (deaths) for the period between 6 April 2001 and 31 December 2009. Results For the vast majority of cancer sites we found an inverse gradient in survival, with the worst survival indicators in the lowest educational group. We estimated that 18.6% of the deaths in Lithuanian cancer patients could have potentially been postponed, if all the patients had the same cancer mortality as the patients with the highest educational level. Conclusion Our findings offer a warning that although the survival rates of cancer patients are improving, this progress hides disparities between different groups of patients. PMID:27070947

  15. Testing a Multigene Signature of Prostate Cancer Death in the Swedish Watchful Waiting Cohort

    OpenAIRE

    Mucci, Lorelei A.; Pawitan, Yudi; DEMICHELIS, Francesca; Fall, Katja; Stark, Jennifer R.; Adami, Hans-Olov; Andersson, Swen-Olof; Andrén, Ove; Eisenstein, Anna; Holmberg, Lars; Huang, Wei; Kantoff, Philip W.; Kim, Robert; Perner, Sven; Stampfer, Meir J

    2008-01-01

    While prostate cancer is a leading cause of cancer death, most men die with and not from their disease, underscoring the urgency to distinguish potentially lethal from indolent prostate cancer. We tested the prognostic value of a previously identified multigene signature of prostate cancer progression to predict cancer-specific death. The Örebro Watchful Waiting Cohort included 172 men with localized prostate cancer of whom 40 died of prostate cancer. We quantified protein expression of the m...

  16. Incidence of cardiac deaths after irradiation for breast cancer

    International Nuclear Information System (INIS)

    The authors ascertained the cause of death of 1489 women who underwent mastectomy for breast cancer from 1959 through 1972. Postmastectomy irradiation, using parasternal portals which treated some heart, was given to 916 of these patients. The usual dose of raction was 45 Gray (4500 rad) in three weeks, a dose previously considered safe. Analysis by lifetable and Cox proportional hazard methods showed an excess of cardiac deaths in the irradiated women (logrank P = .02) even after controlling for age, hospital, calendar year, number of axillary lymph nodes involved, abnormal electrocardiogram, and prior history of heart disease. The excess deaths only occurred more than ten years after irradiation and only in women under age 70 at the time of mastectomy. Limiting analysis to patients age 40 and 69 years at the time of mastectomy, the authors observed that the hazard ratio for cardiac death was 2.24 (90% confidence interval 1.40 to 3.61) for right sided irradiation and 1.95 (90% confidence interval 1.87 to 4.66) for left sided irradiation. They conclude that irradiation of the heart, in doses previously considered safe, predisposes to cardiac death more than ten years later

  17. Breast cancer statistics, 2015: Convergence of incidence rates between black and white women.

    Science.gov (United States)

    DeSantis, Carol E; Fedewa, Stacey A; Goding Sauer, Ann; Kramer, Joan L; Smith, Robert A; Jemal, Ahmedin

    2016-01-01

    In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Approximately 231,840 new cases of invasive breast cancer and 40,290 breast cancer deaths are expected to occur among US women in 2015. Breast cancer incidence rates increased among non-Hispanic black (black) and Asian/Pacific Islander women and were stable among non-Hispanic white (white), Hispanic, and American Indian/Alaska Native women from 2008 to 2012. Although white women have historically had higher incidence rates than black women, in 2012, the rates converged. Notably, during 2008 through 2012, incidence rates were significantly higher in black women compared with white women in 7 states, primarily located in the South. From 1989 to 2012, breast cancer death rates decreased by 36%, which translates to 249,000 breast cancer deaths averted in the United States over this period. This decrease in death rates was evident in all racial/ethnic groups except American Indians/Alaska Natives. However, the mortality disparity between black and white women nationwide has continued to widen; and, by 2012, death rates were 42% higher in black women than in white women. During 2003 through 2012, breast cancer death rates declined for white women in all 50 states; but, for black women, declines occurred in 27 of 30 states that had sufficient data to analyze trends. In 3 states (Mississippi, Oklahoma, and Wisconsin), breast cancer death rates in black women were stable during 2003 through 2012. Widening racial disparities in breast cancer mortality are likely to continue, at least in the short term, in view of the increasing trends in breast cancer incidence rates in black women. PMID:26513636

  18. Regulation of death receptors-Relevance in cancer therapies

    International Nuclear Information System (INIS)

    Apoptosis is an essential non-inflammatory mechanism for cell removal, which occurs during both physiological and pathological conditions. Apoptosis is characteristically executed by cysteine proteases, termed caspases. The most specific way to activate the caspases machinery is through death receptors (DRs), such as the tumor necrosis factor (TNFR), Fas receptor (FasR), and TRAIL (TRAIL-R). The apoptotic signaling is tightly regulated by the balance of pro-apoptotic and anti-apoptotic proteins and an imbalance between cell death and proliferation may cause numerous diseases, including cancers. The intensive research during the past decade has delineated the basic mechanisms of apoptosis and outlined many important molecular mechanisms underlying the regulation of apoptosis. There is also a better understanding of how the regulation of apoptosis can be disturbed in human cancer cells. The interplay between DRs signaling and anticancer drugs has offered new concepts for the development of highly specific therapeutical agents. Here we review the current understanding of the different molecular mechanisms that regulate DR-mediated apoptosis and the defects in apoptotic signaling discovered in cancer cells. In light of this knowledge, new promising target-based agents for future cancer therapies have been developed

  19. 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.

  20. Effect of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality

    Science.gov (United States)

    Zhang, Sui-Liang; Chen, Ting-Song; Ma, Chen-Yun; Meng, Yong-Bin; Zhang, Yu-Fei; Chen, Yi-Wei; Zhou, Yu-Hao

    2016-01-01

    Abstract Background: Observational studies have suggested that vitamin B supplementation is associated with cancer risk, but this association remains controversial. A pooled data-based meta-analysis was conducted to summarize the evidence from randomized controlled trials (RCTs) investigating the effects of vitamin B supplementation on cancer incidence, death due to cancer, and total mortality. Methods: PubMed, EmBase, and the Cochrane Library databases were searched to identify trials to fit our analysis through August 2015. Relative risk (RR) was used to measure the effect of vitamin B supplementation on the risk of cancer incidence, death due to cancer, and total mortality using a random-effect model. Cumulative meta-analysis, sensitivity analysis, subgroup analysis, heterogeneity tests, and tests for publication bias were also conducted. Results: Eighteen RCTs reporting the data on 74,498 individuals were included in the meta-analysis. Sixteen of these trials included 4103 cases of cancer; in 6 trials, 731 cancer-related deaths occurred; and in 15 trials, 7046 deaths occurred. Vitamin B supplementation had little or no effect on the incidence of cancer (RR: 1.04; 95% confidence interval [CI]: 0.98–1.10; P = 0.216), death due to cancer (RR, 1.05; 95% CI: 0.90–1.22; P = 0.521), and total mortality (RR, 1.00; 95% CI: 0.94–1.06; P = 0.952). Upon performing a cumulative meta-analysis for cancer incidence, death due to cancer, and total mortality, the nonsignificance of the effect of vitamin B persisted. With respect to specific types of cancer, vitamin B supplementation significantly reduced the risk of skin melanoma (RR, 0.47; 95% CI: 0.23–0.94; P = 0.032). Conclusion: Vitamin B supplementation does not have an effect on cancer incidence, death due to cancer, or total mortality. It is associated with a lower risk of skin melanoma, but has no effect on other cancers. PMID:27495015

  1. Ovarian Cancer Screening Method Fails to Reduce Deaths from the Disease | Division of Cancer Prevention

    Science.gov (United States)

    New results from the NCI-sponsored Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial show that screening for ovarian cancer with transvaginal ultrasound (TVU) and the CA-125 blood test did not result in fewer deaths from the disease compared with usual care. |

  2. 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

  3. Necroptosis: an alternative cell death program defending against cancer.

    Science.gov (United States)

    Chen, Dongshi; Yu, Jian; Zhang, Lin

    2016-04-01

    One of the hallmarks of cancer is resistance to programmed cell death, which maintains the survival of cells en route to oncogenic transformation and underlies therapeutic resistance. Recent studies demonstrate that programmed cell death is not confined to caspase-dependent apoptosis, but includes necroptosis, a form of necrotic death governed by Receptor-Interacting Protein 1 (RIP1), RIP3, and Mixed Lineage Kinase Domain-Like (MLKL) protein. Necroptosis serves as a critical cell-killing mechanism in response to severe stress and blocked apoptosis, and can be induced by inflammatory cytokines or chemotherapeutic drugs. Genetic or epigenetic alterations of necroptosis regulators such as RIP3 and cylindromatosis (CYLD), are frequently found in human tumors. Unlike apoptosis, necroptosis elicits a more robust immune response that may function as a defensive mechanism by eliminating tumor-causing mutations and viruses. Furthermore, several classes of anticancer agents currently under clinical development, such as SMAC and BH3 mimetics, can promote necroptosis in addition to apoptosis. A more complete understanding of the interplay among necroptosis, apoptosis, and other cell death modalities is critical for developing new therapeutic strategies to enhance killing of tumor cells. PMID:26968619

  4. Mechanism of heavy ion radiation-induced cancer cell death

    International Nuclear Information System (INIS)

    We previously reported that the carbon beam triggers apoptosis in radio-resistant cancer cell lines via extracellular signal-regulated kinase (ERK)- and mitochondrial Bcl-2 family protein-dependant mechanism. Here, we further examined the further apoptosis-inducing mechanism of carbon beam in two glioma cell lines (T98G, U251). ERK1/2 knockdown experiments revealed that ERK regulates this apoptosis-inducing machinery upstream of mitochondria. Furthermore, we also found that both T98G cell and U251 cell stably expressing dominant-negative ERK2 suppress cell death induced by carbon beam irradiation. We also found proapoptotic PUMA and antiapoptotic Bcl-2 dynamically chang their expression levels corresponding to ERK activation after CB irradiation in U251 cell, and knockdown of PUMA decreased CB-induced U251 cell death. These data suggest that kinase action of ERK is essential for CB-induced glioma cell death, and proapoptotic PUMA and antiapoptotic Bcl-2 might be downstream targets of ERK in CB-induced glioma cell death mechanism. (author)

  5. ER Death Rate in U.S. Drops by Nearly Half

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_159738.html ER Death Rate in U.S. Drops by Nearly Half Study ... July 6, 2016 (HealthDay News) -- Hospital emergency room deaths in the United States plummeted by nearly half ...

  6. Rates of TBI-related Deaths by Age Group — United States, 2001–2010

    Data.gov (United States)

    U.S. Department of Health & Human Services — Changes in the rates of TBI-related deaths vary depending on age. For persons 44 years of age and younger, TBI-related deaths decreased between the periods of...

  7. Selective Induction of Cancer Cell Death by Targeted Granzyme B

    Directory of Open Access Journals (Sweden)

    Robert A. Jabulowsky

    2013-02-01

    Full Text Available The potential utility of immunotoxins for cancer therapy has convincingly been demonstrated in clinical studies. Nevertheless, the high immunogenicity of their bacterial toxin domain represents a critical limitation, and has prompted the evaluation of cell-death inducing proteins of human origin as a basis for less immunogenic immunotoxin-like molecules. In this review, we focus on the current status and future prospects of targeted fusion proteins for cancer therapy that employ granzyme B (GrB from cytotoxic lymphocytes as a cytotoxic moiety. Naturally, this serine protease plays a critical role in the immune defense by inducing apoptotic target cell death upon cleavage of intracellular substrates. Advances in understanding of the structure and function of GrB enabled the generation of chimeric fusion proteins that carry a heterologous cell binding domain for recognition of tumor-associated cell surface antigens. These hybrid molecules display high selectivity for cancer cells, with cell killing activities similar to that of corresponding recombinant toxins. Recent findings have helped to understand and circumvent intrinsic cell binding of GrB and susceptibility of the enzyme to inhibition by serpins. This now allows the rational design of optimized GrB derivatives that avoid sequestration by binding to non-target tissues, limit off-target effects, and overcome resistance mechanisms in tumor cells.

  8. Spiritual Values and Death Anxiety: Implications for Counseling With Terminal Cancer Patients.

    Science.gov (United States)

    Gibbs, Harriett Weidman; Achterberg-Lawlis, Jeanne

    1978-01-01

    Results indicate cancer patients depend strongly on perceived strength of religious beliefs and values in coping with imminent death. Low fear of death was associated with previous experience with a dying person. Death anxiety scale score for cancer patients was significantly lower than for other populations. (Author/BEF)

  9. 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. PMID:26250412

  10. 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.

  11. Accounting for Outcome Misclassification in Estimates of the Effect of Occupational Asbestos Exposure on Lung Cancer Death

    OpenAIRE

    Edwards, Jessie K.; Stephen R Cole; Chu, Haitao; Olshan, Andrew F.; Richardson, David B.

    2013-01-01

    In studies of the health effects of asbestos, lung cancer death is subject to misclassification. We used modified maximum likelihood to explore the effects of outcome misclassification on the rate ratio of lung cancer death per 100 fiber-years per milliliter of cumulative asbestos exposure in a cohort study of textile workers in Charleston, South Carolina, followed from 1940 to 2001. The standard covariate-adjusted estimate of the rate ratio was 1.94 (95% confidence interval: 1.55, 2.44), and...

  12. Breast Cancer Patients with High Density Mammograms Do Not Have Increased Risk of Death

    Science.gov (United States)

    ... density mammograms do not have increased risk of death High mammographic breast density, which is a marker ... does not seem to increase the risk of death among breast cancer patients, according to a study ...

  13. Activation of ERK signaling and induction of colon cancer cell death by piperlongumine

    OpenAIRE

    Randhawa, H; Kibble, K; Zeng, H.; Moyer, MP; Reindl, KM

    2013-01-01

    Piperlongumine (PPLGM) is a bioactive compound isolated from long peppers that shows selective toxicity towards a variety of cancer cell types including colon cancer. The signaling pathways that lead to cancer cell death in response to PPLGM exposure have not been previously identified. Our objective was to identify the intracellular signaling mechanisms by which PPLGM leads to enhanced colon cancer cell death. We found that PPLGM inhibited the growth of colon cancer cells in time- and concen...

  14. Prostate Cancer Incidence Rates in Africa

    OpenAIRE

    Sabah M. Quraishi; Hsing, Ann W.; Hongmei Zhang; Jamie Ritchey; Devesa, Susan S.; Chu, Lisa W.

    2011-01-01

    African American men have among the highest prostate cancer incidence rates in the world yet rates among their African counterparts are unclear. In this paper, we compared reported rates among black men of Sub-Saharan African descent using data from the International Agency for Research on Cancer (IARC) and the National Cancer Institute Surveillance, Epidemiology, and End Results Program for 1973–2007. Although population-based data in Africa are quite limited, the available data from IARC sh...

  15. An International Comparison of the Effect of Policy Shifts to Organ Donation following Cardiocirculatory Death (DCD) on Donation Rates after Brain Death (DBD) and Transplantation Rates

    OpenAIRE

    Bendorf, Aric; Kelly, Patrick J.; Kerridge, Ian H; McCaughan, Geoffrey W.; Myerson, Brian; Stewart, Cameron; Pussell, Bruce A

    2013-01-01

    During the past decade an increasing number of countries have adopted policies that emphasize donation after cardiocirculatory death (DCD) in an attempt to address the widening gap between the demand for transplantable organs and the availability of organs from donation after brain death (DBD) donors. In order to examine how these policy shifts have affected overall deceased organ donor (DD) and DBD rates, we analyzed deceased donation rates from 82 countries from 2000–2010. On average, overa...

  16. High death rate in mice treated topically with diclofenac

    DEFF Research Database (Denmark)

    Lerche, Catharina M; Philipsen, Peter A; Poulsen, Thomas;

    2011-01-01

    ). Diclofenac was applied topically on the backs of hairless, female, C3.Cg/TifBomTac immunocompetent mice three times weekly followed by ultraviolet radiation (2, 3, or 4 Standard Erythema Dose) until death. There was a significant difference in survival between diclofenac-treated groups and control groups (P...

  17. Cancer rates after kidney transplantation

    DEFF Research Database (Denmark)

    Sodemann, Ulrik; Bistrup, Claus; Marckmann, Peter

    2011-01-01

    Previous studies demonstrated a 3-5-fold increased cancer risk in kidney allograft recipients compared with the general population. Our aim was to estimate cancer frequencies among kidney allograft recipients who were transplanted in 1997-2000 and who were immunosuppressed according to a more...

  18. Data on the distribution of cancer incidence and death across age and sex groups visualized using multilevel spie charts.

    Science.gov (United States)

    Feitelson, Dror G

    2016-04-01

    Cancer incidence and death statistics are typically recorded for multiple age and sex brackets, leading to large data tables which are difficult to digest. Effective visualizations of this data would allow practitioners, policy makers, and the general public to comprehend the data more readily and act on it appropriately. We introduce multilevel spie charts to create a combined visualization of cancer incidence and death statistics. Spie charts combine multiple pie charts, where the base pie chart (representing the general population) is used to set the angles of slices, and the superimposed ones use variable radii to portray the cancer data. Spie charts of cancer incidence and death statistics from Israel for 2009-2011 are used as an illustration. These charts clearly show various patterns of how cancer incidence and death distribute across age and sex groups, illustrating (1) absolute numbers and (2) rates per 100,000 population for different age and sex brackets. In addition, drawing separate charts for different cancer types illustrates relative mortality, both (3) across cancer types and (4) mortality relative to incidence. Naturally, this graphical depiction can be used for other diseases as well. PMID:26560991

  19. Ovarian Cancer Screening Method Fails to Reduce Deaths from the Disease

    Science.gov (United States)

    New results from the NCI-sponsored PLCO Cancer Screening Trial show that screening for ovarian cancer with transvaginal ultrasound (TVU) and the CA-125 blood test did not result in fewer deaths from the disease compared with usual care.

  20. Estimating the personal cure rate of cancer patients using population-based grouped cancer survival data

    OpenAIRE

    Yu, Binbing; Tiwari, Ram C.; Feuer, Eric J.

    2010-01-01

    Cancer patients are subject to multiple competing risks of death and may die from causes other than the cancer diagnosed. The probability of not dying from the cancer diagnosed, which is one of the patients’ main concerns, is sometimes called the “personal cure” rate. Two approaches of modeling competing-risk survival data, namely the cause-specific hazards approach and the mixture model approach, have been used to model competing-risk survival data. In this article, we first show the connect...

  1. Chinese Medicines Induce Cell Death: The Molecular and Cellular Mechanisms for Cancer Therapy

    OpenAIRE

    Xuanbin Wang; Yibin Feng; Ning Wang; Fan Cheung; Hor Yue Tan; Sen Zhong; Charlie Li; Seiichi Kobayashi

    2014-01-01

    Chinese medicines have long history in treating cancer. With the growing scientific evidence of biomedical researches and clinical trials in cancer therapy, they are increasingly accepted as a complementary and alternative treatment. One of the mechanisms is to induce cancer cell death. Aim. To comprehensively review the publications concerning cancer cell death induced by Chinese medicines in recent years and provide insights on anticancer drug discovery from Chinese medicines. Materials and...

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

    Science.gov (United States)

    Fallahian, Naz Afarin

    .05). No association was found between exposure to transuranic radionuclides and causes of death due to cancer development (alpha = 0.05). However, statistically significant associations were found between the cause of death due to any type of cancer and exposure to benzene or toluene (odds ratio = 5.71; 95% CI: 1.04 to 31.34), as well as smoking habits (odds ratio = 5.41; 95% CI: 1.42 to 20.67), and rate of cigarette smoking (odds ratio = 2.70; 95% CI: 1.37 to 5.30). Lung cancer deaths were found to be related to exposure to chlorinated solvents (odds ratio = 10.85; 95% CI: 1.02 to 115.16), and the duration of exposure to these materials (odds ratio = 1.12; 95% CI: 1.01 to 1.24).

  3. Comparing road traffic mortality rates from police-reported data and death registration data in China

    Directory of Open Access Journals (Sweden)

    Guoqing Hu

    2011-01-01

    Full Text Available OBJECTIVE: To compare death rates from road traffic injuries in China in 2002-2007 when derived from police-reported data versus death registration data. METHODS: In China, police-recorded data are obtained from police records by means of a standardized, closed-ended data collection form; these data are published in the China statistical yearbook of communication and transportation. Official death registration data, on the other hand, are obtained from death certificates completed by physicians and are published in the China health statistics yearbook. We searched both sources for data on road traffic deaths in 2002-2007, used the χ2 test to compare the mortality rates obtained, and performed linear regression to look for statistically significant trends in road traffic mortality over the period. FINDINGS: For 2002-2007, the rate of death from road traffic injuries based on death registration data was about twice as high as the rate reported by the police. Linear regression showed a significant decrease of 27% (95% confidence interval, CI: 35-19 in the death rate over the period according to police sources but no significant change according to death registration data. CONCLUSION: The widely-cited recent drop in road traffic mortality in China, based on police-reported data, may not reflect a genuine decrease. The quality of the data obtained from police reports, which drives decision-making by the Government of China and international organizations, needs to be investigated, monitored and improved.

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

    OpenAIRE

    Geerst, 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 had discussed the impending death with their child, whether they reflected on this discussion positively, their reasons for not discussing death with their child, and the manner in which the conver...

  5. Deaths Rates in Public Hospitals of Eastern Cape Province of South Africa

    Directory of Open Access Journals (Sweden)

    A Nge Okwe

    2012-12-01

    Full Text Available Background: South Africa (SA is experiencing a rapid epidemiologic transition as a consequence of political, economic and social changes. In this study we described, based on hospital data, the mortality patterns of Non communicable Diseases (NCD, Communicable Diseases (CD, the NCD/CD ratios, and the trends of deaths.Methods: We conducted a cross-sectional survey of all deaths occurring in several public hospitals in the Eastern Cape Province of SA between 2002 and 2006. Causes of deaths were coded according to the ICD 10 Edition.Results: A total of 107380 admissions responded to the inclusion criteria between 2002 and 2006. The crude death rate was 4.3% (n=4566 with a mean age of 46±21 years and a sex ratio of 3.1 men (n=3453: 1 woman (n=1113. Out of all deaths, there were 62.9% NCD (n=2872 vs. 37.1% CD (n=1694 with NCD/CD ratio of 1.7. The ratio NCD/CD deaths in men was 1.3 (n=1951/1502 vs. NCD/CD deaths in women of 1.9 (n=735/378. The peak of deaths was observed in winter season. The majority of NCD deaths were at age of 30-64 years, whereas the highest rate of CD deaths was at age< 30 years. The trend of deaths including the majority of NCD, increased from 2002 to 2006. There was a tendency of increase in tuberculosis deaths, but a tendency of decrease in HIV/AIDS deaths was from 2002 to 2006.Conclusion: Non-communicable diseases are the leading causes of deaths in rural Eastern Cape province of SA facing Post-epidemiologic transition stages. We recommend overarching priority actions for the response to the Non-communicable Diseases: policy change, prevention, treatment, international cooperation, research, monitoring, accountability, and re-orientation of health systems.

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

    Science.gov (United States)

    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. PMID:24716627

  7. Mathematical modelling of the death rate dynamics in mammals with intestinal form of radiation sicleness

    International Nuclear Information System (INIS)

    A mathematical models has been developed to describe the death rate dynamics in irradiated mammals. The model links statistical biometric functions with statistical and dynamic characteristics of the organism's 'critical' system. There is an agreement between the results of modelling and experiments with respect to death rate dynamics of small laboratory animals subjected to acute and chronic irradiation with doses and dose-rates at which small intestine epithelium is 'ctitical'

  8. Differences in Age-Standardized Mortality Rates for Avoidable Deaths Based on Urbanization Levels in Taiwan, 1971–2008

    Directory of Open Access Journals (Sweden)

    Brian K. Chen

    2014-02-01

    Full Text Available The World is undergoing rapid urbanization, with 70% of the World population expected to live in urban areas by 2050. Nevertheless, nationally representative analysis of the health differences in the leading causes of avoidable mortality disaggregated by urbanization level is lacking. We undertake a study of temporal trends in mortality rates for deaths considered avoidable by the Concerted Action of the European Community on Avoidable Mortality for four different levels of urbanization in Taiwan between 1971 and 2008. We find that for virtually all causes of death, age-standardized mortality rates (ASMRs were lower in more urbanized than less urbanized areas, either throughout the study period, or by the end of the period despite higher rates in urbanized areas initially. Only breast cancer had consistently higher AMSRs in more urbanized areas throughout the 38-year period. Further, only breast cancer, lung cancer, and ischemic heart disease witnessed an increase in ASMRs in one or more urbanization categories. More urbanized areas in Taiwan appear to enjoy better indicators of health outcomes in terms of mortality rates than less urbanized areas. Access to and the availability of rich healthcare resources in urban areas may have contributed to this positive result.

  9. HPV-Associated Oropharyngeal Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Year Rates by Race and Ethnicity HPV-Associated Anal Cancer HPV-Associated Cervical Cancer HPV-Associated Oropharyngeal Cancers HPV- ... Associated Vulvar Cancer Rates by State HPV-Associated Anal Cancer HPV-Associated Cervical Cancer HPV-Associated Oropharyngeal Cancers HPV- ...

  10. HPV-Associated Vulvar Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Year Rates by Race and Ethnicity HPV-Associated Anal Cancer HPV-Associated Cervical Cancer HPV-Associated Oropharyngeal Cancers HPV- ... Associated Vulvar Cancer Rates by State HPV-Associated Anal Cancer HPV-Associated Cervical Cancer HPV-Associated Oropharyngeal Cancers HPV- ...

  11. 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...... had died from 1 March to 30 November 2006 and were identified through merging of health registers. Relatives returned 198 questionnaires about patients' preferred place-of-death, GPs 333 and CNs 201. The study showed that most terminally ill cancer patients preferred home death (up to 80.7%). The...

  12. Cell Death Pathways in Photodynamic Therapy of Cancer

    International Nuclear Information System (INIS)

    Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases) are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2) are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT

  13. Cell Death Pathways in Photodynamic Therapy of Cancer

    Directory of Open Access Journals (Sweden)

    Michael R. Hamblin

    2011-06-01

    Full Text Available Photodynamic therapy (PDT is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2 are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT.

  14. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012, Region 7 - Kansas City

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for motor vehicle occupants killed in crashes, 2012 Source: Fatality Analysis Reporting System (FARS) Note:...

  15. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012, Region 5 - Chicago

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for motor vehicle occupants killed in crashes, 2012 Source: Fatality Analysis Reporting System (FARS) Note:...

  16. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012, Region 10 - Seattle

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for motor vehicle occupants killed in crashes, 2012 Source: Fatality Analysis Reporting System (FARS) Note:...

  17. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012, Region 2 - New York

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for motor vehicle occupants killed in crashes, 2012 Source: Fatality Analysis Reporting System (FARS) Note:...

  18. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012, HHS Region 1 - Boston

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for motor vehicle occupants killed in crashes, 2012 Source: Fatality Analysis Reporting System (FARS) Note:...

  19. Impaired Driving Death Rate, by Age and Gender, 2012, Region 4 - Atlanta

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for people killed in crashes involving a driver with BAC =>0.08%, 2012 Source: Fatality Analysis Reporting...

  20. Impaired Driving Death Rate, by Age and Gender, 2012, Region 6 - Dallas

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for people killed in crashes involving a driver with BAC =>0.08%, 2012 Source: Fatality Analysis Reporting...

  1. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012, All States

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for motor vehicle occupants killed in crashes, 2012 Source: Fatality Analysis Reporting System (FARS) Note:...

  2. Impaired Driving Death Rate, by Age and Gender, 2012, Region 10 - Seattle

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for people killed in crashes involving a driver with BAC =>0.08%, 2012 Source: Fatality Analysis Reporting...

  3. Impaired Driving Death Rate, by Age and Gender, 2012 & 2014, All States

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for people killed in crashes involving a driver with BAC =>0.08%, 2012. 2012 Source: Fatality Analysis...

  4. Impaired Driving Death Rate, by Age and Gender, 2012, Region 2 - New York

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for people killed in crashes involving a driver with BAC =>0.08%, 2012 Source: Fatality Analysis Reporting...

  5. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012, Region 4 - Atlanta

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for motor vehicle occupants killed in crashes, 2012 Source: Fatality Analysis Reporting System (FARS) Note:...

  6. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012, Region 8 - Denver

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for motor vehicle occupants killed in crashes, 2012 Source: Fatality Analysis Reporting System (FARS) Note:...

  7. Impaired Driving Death Rate, by Age and Gender, 2012, Region 1 - Boston

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for people killed in crashes involving a driver with BAC =>0.08%, 2012 Source: Fatality Analysis Reporting...

  8. Impaired Driving Death Rate, by Age and Gender, 2012, Region 8 - Denver

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for people killed in crashes involving a driver with BAC =>0.08%, 2012 Source: Fatality Analysis Reporting...

  9. Impaired Driving Death Rate, by Age and Gender, 2012, Region 9 - San Francisco

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for people killed in crashes involving a driver with BAC =>0.08%, 2012 Source: Fatality Analysis Reporting...

  10. Impaired Driving Death Rate, by Age and Gender, 2012, Region 5 - Chicago

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for people killed in crashes involving a driver with BAC =>0.08%, 2012 Source: Fatality Analysis Reporting...

  11. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012, Region 3 - Philadelphia

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for motor vehicle occupants killed in crashes, 2012 Source: Fatality Analysis Reporting System (FARS) Note:...

  12. Impaired Driving Death Rate, by Age and Gender, 2012, Region 7 - Kansas City

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for people killed in crashes involving a driver with BAC =>0.08%, 2012 Source: Fatality Analysis Reporting...

  13. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012, Region 6 - Dallas

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for motor vehicle occupants killed in crashes, 2012 Source: Fatality Analysis Reporting System (FARS) Note:...

  14. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012, Region 9 - San Francisco

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for motor vehicle occupants killed in crashes, 2012 Source: Fatality Analysis Reporting System (FARS) Note:...

  15. Impaired Driving Death Rate, by Age and Gender, 2012, Region 3 - Philadelphia

    Data.gov (United States)

    U.S. Department of Health & Human Services — Rate of deaths by age/gender (per 100,000 population) for people killed in crashes involving a driver with BAC =>0.08%, 2012 Source: Fatality Analysis Reporting...

  16. Widely Used Type 2 Diabetes Drug May Reduce Cancer Death Risk

    Science.gov (United States)

    ... news/fullstory_158338.html Widely Used Type 2 Diabetes Drug May Reduce Cancer Death Risk Older women taking metformin saw a ... study found that for women with type 2 diabetes and cancer, the odds of dying from cancer appeared to ...

  17. Activation of ERK signaling and induction of colon cancer cell death by piperlongumine.

    Science.gov (United States)

    Randhawa, H; Kibble, K; Zeng, H; Moyer, M P; Reindl, K M

    2013-09-01

    Piperlongumine (PPLGM) is a bioactive compound isolated from long peppers that shows selective toxicity towards a variety of cancer cell types including colon cancer. The signaling pathways that lead to cancer cell death in response to PPLGM exposure have not been previously identified. Our objective was to identify the intracellular signaling mechanisms by which PPLGM leads to enhanced colon cancer cell death. We found that PPLGM inhibited the growth of colon cancer cells in time- and concentration-dependent manners, but was not toxic toward normal colon mucosal cells at concentrations below 10 μM. Acute (0-60 min) and prolonged (24h) exposure of HT-29 cells to PPLGM resulted in phosphorylation of ERK. To investigate whether ERK signaling was involved in PPLGM-mediated cell death, we treated HT-29 cells with the MEK inhibitor U0126, prior to treating with PPLGM. We found that U0126 attenuated PPLGM-induced activation of ERK and partially protected against PPLGM-induced cell death. These results suggest that PPLGM works, at least in part, through the MEK/ERK pathway to result in colon cancer cell death. A more thorough understanding of the molecular mechanisms by which PPLGM induces colon cancer cell death will be useful in developing therapeutic strategies to treat colon cancer. PMID:23603476

  18. Unlocking Pandora's box: personalising cancer cell death in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Fennell Dean A

    2012-06-01

    Full Text Available Abstract Evasion of apoptosis is a hallmark of tumorigenesis and a recognised cause of multidrug resistance. Over the last decade, insights into how apoptosis might be exploited in non-small cell lung cancer (NSCLC and how cancer therapeutics might be used to engage apoptotic signalling in a personalised manner have changed markedly. We are now in the wake of a paradigm shift in stratified therapeutic approaches related to NSCLC. At the heart of this shift in thinking is the emerging knowledge that even the most drug-resistant cancers exhibit a functional death pathway and, critically, that this pathway can be efficiently engaged, leading to clinical benefit. This review will summarise current knowledge of mitochondrial apoptotic pathway dysfunction in NSCLC and how the next generation of targeted therapeutics might be used to exploit deficiencies in apoptotic signalling in a personalised manner to improve clinical outcome and predict therapeutic benefit.

  19. Effect of marital status on death rates. Part 1: High accuracy exploration of the Farr-Bertillon effect

    Science.gov (United States)

    Richmond, Peter; Roehner, Bertrand M.

    2016-05-01

    The Farr-Bertillon law says that for all age-groups the death rate of married people is lower than the death rate of people who are not married (i.e. single, widowed or divorced). Although this law has been known for over 150 years, it has never been established with well-controlled accuracy (e.g. error bars). This even let some authors argue that it was a statistical artifact. It is true that the data must be selected with great care, especially for age groups of small size (e.g. widowers under 25). The observations reported in this paper were selected in the way experiments are designed in physics, that is to say with the objective of minimizing error bars. Data appropriate for mid-age groups may be unsuitable for young age groups and vice versa. The investigation led to the following results. (1) The FB effect is very similar for men and women, except that (at least in western countries) its amplitude is 20% higher for men. (2) There is a marked difference between single/divorced persons on the one hand, for whom the effect is largest around the age of 40, and widowed persons on the other hand, for whom the effect is largest around the age of 25. (3) When different causes of death are distinguished, the effect is largest for suicide and smallest for cancer. For heart disease and cerebrovascular accidents, the fact of being married divides the death rate by 2.2 compared to non-married persons. (4) For young widowers the death rates are up to 10 times higher than for married persons of same age. This extreme form of the FB effect will be referred to as the "young widower effect". Chinese data are used to explore this effect more closely. A possible connection between the FB effect and Martin Raff's "Stay alive" effect for the cells in an organism is discussed in the last section.

  20. An international comparison of the effect of policy shifts to organ donation following cardiocirculatory death (DCD on donation rates after brain death (DBD and transplantation rates.

    Directory of Open Access Journals (Sweden)

    Aric Bendorf

    Full Text Available During the past decade an increasing number of countries have adopted policies that emphasize donation after cardiocirculatory death (DCD in an attempt to address the widening gap between the demand for transplantable organs and the availability of organs from donation after brain death (DBD donors. In order to examine how these policy shifts have affected overall deceased organ donor (DD and DBD rates, we analyzed deceased donation rates from 82 countries from 2000-2010. On average, overall DD, DBD and DCD rates have increased over time, with the proportion of DCD increasing 0.3% per year (p = 0.01. Countries with higher DCD rates have, on average, lower DBD rates. For every one-per million population (pmp increase in the DCD rate, the average DBD rate decreased by 1.02 pmp (95% CI: 0.73, 1.32; p<0.0001. We also found that the number of organs transplanted per donor was significantly lower in DCD when compared to DBD donors with 1.51 less transplants per DCD compared to DBD (95% CI: 1.23, 1.79; p<0.001. Whilst the results do not infer a causal relationship between increased DCD and decreased DBD rates, the significant correlation between higher DCD and lower DBD rates coupled with the reduced number of organs transplanted per DCD donor suggests that a national policy focus on DCD may lead to an overall reduction in the number of transplants performed.

  1. Prostate cancer incidence rates in Africa.

    Science.gov (United States)

    Chu, Lisa W; Ritchey, Jamie; Devesa, Susan S; Quraishi, Sabah M; Zhang, Hongmei; Hsing, Ann W

    2011-01-01

    African American men have among the highest prostate cancer incidence rates in the world yet rates among their African counterparts are unclear. In this paper, we compared reported rates among black men of Sub-Saharan African descent using data from the International Agency for Research on Cancer (IARC) and the National Cancer Institute Surveillance, Epidemiology, and End Results Program for 1973-2007. Although population-based data in Africa are quite limited, the available data from IARC showed that rates among blacks were highest in the East (10.7-38.1 per 100,000 man-years, age-adjusted world standard) and lowest in the West (4.7-19.8). These rates were considerably lower than those of 80.0-195.3 observed among African Americans. Rates in Africa increased over time (1987-2002) and have been comparable to those for distant stage in African Americans. These patterns are likely due to differences between African and African American men in medical care access, screening, registry quality, genetic diversity, and Westernization. Incidence rates in Africa will likely continue to rise with improving economies and increasing Westernization, warranting the need for more high-quality population-based registration to monitor cancer incidence in Africa. PMID:22111004

  2. High dose rate brachytherapy for oral cancer

    International Nuclear Information System (INIS)

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. (author)

  3. Colonoscopy Reduces Risk of Death from Colorectal Cancer in High-Risk Patients

    Science.gov (United States)

    Long-term results from the National Polyp Study confirm that removing precancerous adenomas not only reduces the risk of colorectal cancer but also reduces the number of deaths from the disease by more than half.

  4. Serum carotenoid levels and risk of lung cancer death in US adults

    OpenAIRE

    Min, Kyoung-Bok; Min, Jin-Young

    2014-01-01

    Lung cancer is one of the most common cancers worldwide and is the leading cause of cancer-induced death in the USA. Although much attention has been focused on the anti-carcinogenic effect of consuming carotenoid-containing food or supplements, the results have been inconsistent. We investigated whether serum carotenoid levels were associated with the mortality risk of lung cancer in US adults using data from a nationally representative sample. The data were obtained from the Third Nutrition...

  5. Stillbirth and neonatal death among female cancer survivors: A national cohort study.

    Science.gov (United States)

    Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

    2016-09-01

    The number of cancer survivors continues to increase worldwide. Many of these survivors have had children of their own. It is less well-known whether radiation therapy or chemotherapy could affect the risk of stillbirth and neonatal death for these children. To explore this research questions, we identified all women diagnosed with cancer between 1958 and 2012 from the Swedish Cancer Register and they were further linked to the Swedish Medical Birth Register to identify their subsequent child birth between 1973 and 2012. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals for the association between stillbirth and neonatal death and maternal cancer diagnosis. As compared to the children without maternal cancer, the risk of stillbirth was significantly higher among children of female cancer survivors born within three years after cancer diagnosis with an OR of 1.92 (95% CI 1.03-3.57). The incidence of neonatal death did not show a significant change. For women with more than one pregnancy after cancer diagnosis, the risk of stillbirth and neonatal death was lower for the second child birth compared to the first child birth. Our study suggested that the risk of stillbirth was negatively associated with the time after cancer diagnosis, providing evidence that the adverse effect associated with cancer treatment may diminish with time. PMID:27101797

  6. 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.

  7. Grief Responses of Turkish Families after the Death of Their Children from Cancer

    Science.gov (United States)

    Cimete, Guler; Kuguoglu, Sema

    2006-01-01

    The aim of this qualitative study was to determine what the emotional reactions, experiences, and coping and support systems of families would be after the death of their children from cancer. The sample comprised 19 family members from five families. At the time of the interviews, it had been 8-14 months since the death of their children. The…

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

    OpenAIRE

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

    2009-01-01

    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...

  9. 38 CFR 3.22 - DIC benefits for survivors of certain veterans rated totally disabled at time of death.

    Science.gov (United States)

    2010-07-01

    ... survivors of certain veterans rated totally disabled at time of death. 3.22 Section 3.22 Pensions, Bonuses... disabled at time of death. (a) Even though a veteran died of non-service-connected causes, VA will pay death benefits to the surviving spouse or children in the same manner as if the veteran's death...

  10. Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death

    International Nuclear Information System (INIS)

    Recent research has revealed that targeting mitochondrial bioenergetic metabolism is a promising chemotherapeutic strategy. Key to successful implementation of this chemotherapeutic strategy is the use of new and improved mitochondria-targeted cationic agents that selectively inhibit energy metabolism in breast cancer cells, while exerting little or no long-term cytotoxic effect in normal cells. In this study, we investigated the cytotoxicity and alterations in bioenergetic metabolism induced by mitochondria-targeted vitamin E analog (Mito-chromanol, Mito-ChM) and its acetylated ester analog (Mito-ChMAc). Assays of cell death, colony formation, mitochondrial bioenergetic function, intracellular ATP levels, intracellular and tissue concentrations of tested compounds, and in vivo tumor growth were performed. Both Mito-ChM and Mito-ChMAc selectively depleted intracellular ATP and caused prolonged inhibition of ATP-linked oxygen consumption rate in breast cancer cells, but not in non-cancerous cells. These effects were significantly augmented by inhibition of glycolysis. Mito-ChM and Mito-ChMAc exhibited anti-proliferative effects and cytotoxicity in several breast cancer cells with different genetic background. Furthermore, Mito-ChM selectively accumulated in tumor tissue and inhibited tumor growth in a xenograft model of human breast cancer. We conclude that mitochondria-targeted small molecular weight chromanols exhibit selective anti-proliferative effects and cytotoxicity in multiple breast cancer cells, and that esterification of the hydroxyl group in mito-chromanols is not a critical requirement for its anti-proliferative and cytotoxic effect

  11. Cell Death Pathways and Phthalocyanine as an Efficient Agent for Photodynamic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Ivan Mfouo-Tynga

    2015-05-01

    Full Text Available The mechanisms of cell death can be predetermined (programmed or not and categorized into apoptotic, autophagic and necrotic pathways. The process of Hayflick limits completes the execution of death-related mechanisms. Reactive oxygen species (ROS are associated with oxidative stress and subsequent cytodamage by oxidizing and degrading cell components. ROS are also involved in immune responses, where they stabilize and activate both hypoxia-inducible factors and phagocytic effectors. ROS production and presence enhance cytodamage and photodynamic-induced cell death. Photodynamic cancer therapy (PDT uses non-toxic chemotherapeutic agents, photosensitizer (PS, to initiate a light-dependent and ROS-related cell death. Phthalocyanines (PCs are third generation and stable PSs with improved photochemical abilities. They are effective inducers of cell death in various neoplastic models. The metallated PCs localize in critical cellular organelles and are better inducers of cell death than other previous generation PSs as they favor mainly apoptotic cell death events.

  12. Heart rate variability characterized by refined multiscale entropy applied to cardiac death in ischemic cardiomyopathy patients

    OpenAIRE

    Caminal Magrans, Pere; Valencia Murillo, José Fernando; Vallverdú Ferrer, Montserrat; Schroeder, Rico; Cygankiewicz, I.; Vázquez, Rafael; Bayes de Luna, Antonio; Porta, Alberto; Voss, Andreas

    2010-01-01

    In this work, Refined Multiscale Entropy (RMSE) was applied to characterize risk of cardiac death in ischemic cardiomyopathy patients, analyzing heart rate variability (HRV) by means of RR series during daytime and nighttime. RMSE approach measures an entropy rate in different time scales of a series, giving a multiscale characterization of complexity of that series. RMSE showed statistically significant differences (p

  13. Improving surgical resection rate in lung cancer

    OpenAIRE

    Laroche, C.; Wells, F; Coulden, R.; Stewart, S; Goddard, M; Lowry, E.; Price, A; Gilligan, D.

    1998-01-01

    BACKGROUND—Surgical resection is the recognised treatment of choice for patients with stage I or II non-small cell lung cancer (NSCLC). In the UK surgical resection rates have remained far lower (20%), despite the recent introduction of fast access investigation units. It remains unclear therefore why UK surgical resection rates lag so far behind those of other countries.
METHODS—A new quick access two stop investigation service was established at Papworth in November 199...

  14. Gossypol Induced Cell Death in DU 145 Prostate Cancer Cells

    OpenAIRE

    Kennelly, Susan

    2010-01-01

    Cancer Biology Tumourigenesis is a multistep process which includes the transformation of healthy cells into extremely malignant cells, caused by the disruption of normal tissue homeostasis. Hanahan and Weinberg propose that there are a common set of 'acquired capabilities' that most if not all cancers posses's in order to survive and proliferate despite changes in their normal cell physiology during cancer development (Hanahan and Weinberg, 2000). These "Hallmarks of Cancer", according to...

  15. 不同治疗方案与局部晚期前列腺癌患者前列腺特异性抗原进展及生存状况的Meta分析%Meta-analysis of randomized trials of prostate specific antigen progression and death rate in patients with locally advanced prostate cancer

    Institute of Scientific and Technical Information of China (English)

    徐勇; 刘冉录; 齐士勇; 张志宏; 赵维明

    2008-01-01

    Objective To verify the best treatment strategy in reducing prostate specific antigen (PSA) progression and death rate in patients with locally advanced prostate cancer by a meta-analysis. Methods The literature search strategy was followed according to the Collaborative Review Group search strategy. Published data of randomized clinical trials comparing radical prostatectomy (RP) plus adjuvant therapy to either RP alone or other treatment were analyzed. Both fixed effect model and randomized effect model were applied and odds ratio (OR) with its 95% confidence interval (95% CI) was also used as the effect size 'estimate. Results Eight clinical trials were chosen with total in-volved cases of 3826. There were 5 trials compared post radical prostatectomy plus adjuvant hormonal therapy with radical prostatectomy alone. PSA progression was used as the indicator of progression and the combined OR was 0.86 (95%CI 0.48-1.56). There were 3 trails compared the combination of radical prostateetomy with hormonal therapy and radical prostatectomy alone. Disease specific death rate was used as the evaluating criteria and the OR was 0.72(95%CI,0.51-1.02). Conclusion RP plus adjuvant hormonal therapy can reduce PSA progression of patients with locally advanced pros-tate cancer, but it has no significant effect on disease specific death rate.%目的 应用Meta分析探讨不同治疗方案对局部晚期前列腺癌前列腺特异性抗原(PSA)进展及生存状况的影响. 方法制订原始文献的纳入标准、剔除标准及检索策略.以优势比(OR)及其95%可信区间(95%CI)为效应尺度,应用Meta分析固定效应模型和随机效应模型对有关治疗局部晚期前列腺癌不同方案的纳入文献进行综合定量评价. 结果 符合纳入标准的8篇文献进入Meta分析,共3826例.5篇为前列腺根治性切除术(RP)联合辅助治疗与单纯用RP或不用RP进行比较,以PSA进展率为评价指标,合并后的OR值为0.86,95%CI为0.48~1

  16. Trends in corrected lung cancer mortality rates in Brazil and regions

    Science.gov (United States)

    Malta, Deborah Carvalho; de Abreu, Daisy Maria Xavier; de Moura, Lenildo; Lana, Gustavo C; Azevedo, Gulnar; França, Elisabeth

    2016-01-01

    ABSTRACT OBJECTIVE To describe the trend in cancer mortality rates in Brazil and regions before and after correction for underreporting of deaths and redistribution of ill-defined and nonspecific causes. METHODS The study used data of deaths from lung cancer among the population aged from 30 to 69 years, notified to the Mortality Information System between 1996 and 2011, corrected for underreporting of deaths, non-registered sex and age , and causes with ill-defined or garbage codes according to sex, age, and region. Standardized rates were calculated by age for raw and corrected data. An analysis of time trend in lung cancer mortality was carried out using the regression model with autoregressive errors. RESULTS Lung cancer in Brazil presented higher rates among men compared to women, and the South region showed the highest death risk in 1996 and 2011. Mortality showed a trend of reduction for males and increase for women. CONCLUSIONS Lung cancer in Brazil presented different distribution patterns according to sex, with higher rates among men and a reduction in the mortality trend for men and increase for women. PMID:27355467

  17. Low dose irradiation reduces cancer mortality rates

    International Nuclear Information System (INIS)

    Low doses of ionizing radiation stimulate development, growth, memory, sensual acuity, fecundity, and immunity (Luckey, T.D., ''Radiation Hormesis'', CRC Press, 1991). Increased immune competence reduces cancer mortality rates and provides increased average lifespan in animals. Decreased cancer mortality rates in atom bomb victims who received low dose irradiation makes it desirable to examine populations exposed to low dose irradiation. Studies with over 300,000 workers and 7 million person-years provide a valid comparison of radiation exposed and control unclear workers (Luckey, T.D., Nurture with Ionizing Radiation, Nutrition and Cancer, 34:1-11, 1999). Careful selection of controls eliminated any ''healthy worker effect''. The person-year corrected average indicated the cancer mortality rate of exposed workers was only 51% that of control workers. Lung cancer mortality rates showed a highly significant negative correlation with radon concentrations in 272,000 U.S. homes (Cohen, B.L., Health Physics 68:157-174, 1995). In contrast, radon concentrations showed no effect on lung cancer rates in miners from different countries (Lubin, J.H. Am. J. Epidemiology 140:323-332, 1994). This provides evidence that excessive lung cancer in miners is caused by particulates (the major factor) or toxic gases. The relative risk for cancer mortality was 3.7% in 10,000 Taiwanese exposed to low level of radiation from 60Co in their steel supported homes (Luan, Y.C. et al., Am. Nuclear Soc. Trans. Boston, 1999). This remarkable finding needs further study. A major mechanism for reduced cancer mortality rates is increased immune competence; this includes both cell and humoral components. Low dose irradiation increases circulating lymphocytes. Macrophage and ''natural killer'' cells can destroy altered (cancer) cells before the mass becomes too large. Low dose irradiation also kills suppressor T-cells; this allows helper T-cells to activate killer cells and antibody producing cells

  18. Low dose irradiation reduces cancer mortality rates

    Energy Technology Data Exchange (ETDEWEB)

    Luckey, T.D.

    2000-05-01

    Low doses of ionizing radiation stimulate development, growth, memory, sensual acuity, fecundity, and immunity (Luckey, T.D., ''Radiation Hormesis'', CRC Press, 1991). Increased immune competence reduces cancer mortality rates and provides increased average lifespan in animals. Decreased cancer mortality rates in atom bomb victims who received low dose irradiation makes it desirable to examine populations exposed to low dose irradiation. Studies with over 300,000 workers and 7 million person-years provide a valid comparison of radiation exposed and control unclear workers (Luckey, T.D., Nurture with Ionizing Radiation, Nutrition and Cancer, 34:1-11, 1999). Careful selection of controls eliminated any ''healthy worker effect''. The person-year corrected average indicated the cancer mortality rate of exposed workers was only 51% that of control workers. Lung cancer mortality rates showed a highly significant negative correlation with radon concentrations in 272,000 U.S. homes (Cohen, B.L., Health Physics 68:157-174, 1995). In contrast, radon concentrations showed no effect on hlumg cancer rates in miners from different countries (Lubin, J.H. Am. J. Epidemiology 140:323-332, 1994). This provides evidence that excessive lung cancer in miners is caused by particulates (the major factor) or toxic gases. The relative risk for cancer mortality was 3.7% in 10,000 Taiwanese exposed to low level of radiation from {sup 60}Co in their steel supported homes (Luan, Y.C. et al., Am. Nuclear Soc. Trans. Boston, 1999). This remarkable finding needs further study. A major mechanism for reduced cancer mortality rates is increased immune competence; this includes both cell and humoral components. Low dose irradiation increases circulating lymphocytes. Macrophage and ''natural killer'' cells can destroy altered (cancer) cells before the mass becomes too large. Low dose irradiation also kills suppressor T-cells; this allows

  19. Chinese Medicines Induce Cell Death: The Molecular and Cellular Mechanisms for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Xuanbin Wang

    2014-01-01

    Full Text Available Chinese medicines have long history in treating cancer. With the growing scientific evidence of biomedical researches and clinical trials in cancer therapy, they are increasingly accepted as a complementary and alternative treatment. One of the mechanisms is to induce cancer cell death. Aim. To comprehensively review the publications concerning cancer cell death induced by Chinese medicines in recent years and provide insights on anticancer drug discovery from Chinese medicines. Materials and Methods. Chinese medicines (including Chinese medicinal herbs, animal parts, and minerals were used in the study. The key words including “cancer”, “cell death”, “apoptosis”, “autophagy,” “necrosis,” and “Chinese medicine” were used in retrieval of related information from PubMed and other databases. Results. The cell death induced by Chinese medicines is described as apoptotic, autophagic, or necrotic cell death and other types with an emphasis on their mechanisms of anticancer action. The relationship among different types of cell death induced by Chinese medicines is critically reviewed and discussed. Conclusions. This review summarizes that CMs treatment could induce multiple pathways leading to cancer cell death, in which apoptosis is the dominant type. To apply these preclinical researches to clinic application will be a key issue in the future.

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

    NARCIS (Netherlands)

    Geerst, 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

  1. Last Breath: Art Therapy with a Lung Cancer Patient Facing Imminent Death

    Science.gov (United States)

    Furman, Lisa R.

    2011-01-01

    Art therapy can be an effective way to focus on end of life issues with cancer patients facing imminent death. This viewpoint discusses ethical challenges in the treatment of a 63-year-old man with terminal lung cancer who was participating in short-term individual art therapy. Difficult issues that often surface in the final days of life may…

  2. 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

  3. Nonlinear fluctuation-induced rate equations for linear birth-death processes

    International Nuclear Information System (INIS)

    The Fock-space approach to the solution of master equations for the one-step Markov processes is reconsidered. It is shown that in birth-death processes with an absorbing state at the bottom of the occupation-number spectrum and occupation-number independent annihilation probability occupation-number fluctuations give rise to rate equations drastically different from the polynomial form typical of birth-death processes. The fluctuation-induced rate equations with the characteristic exponential terms are derived for Mikhailov's ecological model and Lanchester's model of modern warfare

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

    OpenAIRE

    Kobori Eiko; Hagihara Akihito; Maeda Yuko; Nakayama Takeo

    2006-01-01

    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...

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

    International Nuclear Information System (INIS)

    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

  6. Apoptotic Death of Prostate Cancer Cells by a Gonadotropin-Releasing Hormone-II Antagonist

    OpenAIRE

    Park, Sumi; Han, Ji Man; Cheon, Jun; Hwang, Jong-Ik; Seong, Jae Young

    2014-01-01

    Gonadotropin-releasing hormone-I (GnRH-I) has attracted strong attention as a hormonal therapeutic tool, particularly for androgen-dependent prostate cancer patients. However, the androgen-independency of the cancer in advanced stages has spurred researchers to look for new medical treatments. In previous reports, we developed the GnRH-II antagonist Trp-1 to inhibit proliferation and stimulate the autophagic death of various prostate cancer cells, including androgen-independent cells. We furt...

  7. Clinical and epidemiological profile of cases of deaths from stomach cancer in the National Cancer Institute, Brazil

    OpenAIRE

    Guedes, Maria Teresa dos Santos; de Jesus, José Paulo; de Souza Filho, Odilon; Fontenele, Raquel Malta; Sousa, Ana Inês

    2014-01-01

    Introduction Stomach cancer is the third most common cause of death worldwide, mainly affecting people with low socioeconomic status. In Brazil, we expect 20,390 new cases of stomach cancer in 2014, in both sexes, and according to the proportional distribution of the ten most prevalent types of cancer (except non-melanoma skin cancer) expected for 2014, this type of cancer was estimated to be the fourth most common in men and sixth in women. Aim To investigate and analyse the clinical and epi...

  8. Induction of Cancer Cell Death by Isoflavone: The Role of Multiple Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Fazlul H. Sarkar

    2011-10-01

    Full Text Available Soy isoflavones have been documented as dietary nutrients broadly classified as “natural agents” which plays important roles in reducing the incidence of hormone-related cancers in Asian countries, and have shown inhibitory effects on cancer development and progression in vitro and in vivo, suggesting the cancer preventive or therapeutic activity of soy isoflavones against cancers. Emerging experimental evidence shows that isoflavones could induce cancer cell death by regulating multiple cellular signaling pathways including Akt, NF-κB, MAPK, Wnt, androgen receptor (AR, p53 and Notch signaling, all of which have been found to be deregulated in cancer cells. Therefore, homeostatic regulation of these important cellular signaling pathways by isoflavones could be useful for the activation of cell death signaling, which could result in the induction of apoptosis of both pre-cancerous and/or cancerous cells without affecting normal cells. In this article, we have attempted to summarize the current state-of-our-knowledge regarding the induction of cancer cell death pathways by isoflavones, which is believed to be mediated through the regulation of multiple cellular signaling pathways. The knowledge gained from this article will provide a comprehensive view on the molecular mechanism(s by which soy isoflavones may exert their effects on the prevention of tumor progression and/or treatment of human malignancies, which would also aid in stimulating further in-depth mechanistic research and foster the initiation of novel clinical trials.

  9. Violent Death Rates and Risk for Released Prisoners in North Carolina.

    Science.gov (United States)

    Lize, Steven Edward; Scheyett, Anna M; Morgan, Candice R; Proescholdbell, Scott K; Norwood, Tammy; Edwards, David

    2015-01-01

    Released prisoners face high risk of early mortality. The risk of violent death, specifically homicide and suicide, are addressed in this study. Data on inmates released from the North Carolina Division of Adult Corrections (N = 476) matched to the Violent Death Reporting System are analyzed to estimate rates and demographic and criminal justice-related predictors. Violent death rates for persons released from prison were more than 7 times higher than for the general adult population. Results from multinomial logistic regression indicate decreased homicide risk for every year of age, whereas male gender and minority race increased risk. For suicide, minority race, release without supervision, and substance abuse treatment in prison decreased fatality risk. By contrast, a history of mental illness increased suicide risk. Implications for practice and research are discussed. PMID:26440107

  10. Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage

    OpenAIRE

    Dhillon, Harsharan; Chikara, Shireen; Reindl, Katie M.

    2014-01-01

    Pancreatic cancer is one of the most deadly cancers with a nearly 95% mortality rate. The poor response of pancreatic cancer to currently available therapies and the extremely low survival rate of pancreatic cancer patients point to a critical need for alternative therapeutic strategies. The use of reactive oxygen species (ROS)-inducing agents has emerged as an innovative and effective strategy to treat various cancers. In this study, we investigated the potential of a known ROS inducer, pipe...

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

    Science.gov (United States)

    Neergaard, Mette Asbjoern; Jensen, Anders Bonde; Sondergaard, Jens; Sokolowski, Ineta; Olesen, Frede; Vedsted, Peter

    2011-12-01

    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 relatives, general practitioners (GPs) and community nurses (CNs) and to assess the agreement of their accounts. The study was a population-based, cross-sectional combined register and questionnaire study in Aarhus County, Denmark. The population comprised 599 deceased adult cancer patients who had died from 1 March to 30 November 2006 and were identified through merging of health registers. Relatives returned 198 questionnaires about patients' preferred place-of-death, GPs 333 and CNs 201. The study showed that most terminally ill cancer patients preferred home death (up to 80.7%). The reported preference for home death weakened as death approached (down to 64.4%). A better congruence was seen between relatives' and GPs' accounts of preference for place of death at the end of the palliative period (κ 0.71) than between relatives' and CNs' accounts (κ 0.37). In conclusion, bereaved relatives (and 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 the agreement between relatives' and CNs' accounts at the same time was significantly less outspoken. This indicates that CNs may be facing a problem in assessing their patients' wishes retrospectively. PMID:21362004

  12. Risk Factors and Control Strategies for the Rapidly Rising Rate of Breast Cancer in Korea

    OpenAIRE

    Park, Sue K.; Kim, Yeonju; Kang, Daehee; Jung, En-Joo; Yoo, Keun-Young

    2011-01-01

    Due to the aging population and tremendous changes in life style over the past decades, cancer has been the leading cause of death in Korea. The incidence rate of breast cancer is the second highest in Korea, and it has shown an annual increase of 6.8% for the past 6 years. The major risk factors of breast cancer in Korean women are as follows: Early menarche, late menopause, late full-term pregnancy (FTP), and low numbers of FTP. Height and body mass index increased the risk of breast cancer...

  13. Rating the elderly with terminal cancer disease

    International Nuclear Information System (INIS)

    Full text: Introduction: In over 60 years are diagnosed more than 50% of tumors and 60% die because of this that only represents 20 % the total number of successes in this population group. However, currently there are few non-oncology geriatric patients who benefit of this model of care. This is because, in addition to palliative care have been developed mainly since Oncology, to it difficult to establish the concept of not being able to complete their basic survival and to predict the final stages of the disease chronicles are made ​​by different disciplines The intention of this study is to evaluate the variety oncology in the Department of Oncology at University Hospital and the focus on the Rating and care have been given to elderly patients with end-stage neoplastic disease or who are liable to care palliative for various reasons. Objective: • Determine the epidemiological profile of older adults with terminal cancer diagnosis attending Department of Hospital Oncology Clinic and if were evaluated globally and received palliative care. Methodology: • Design: Observational descriptive retrospective analytical component. • Universe: Young adults of both sexes attending the Oncology Department of the Hospital de Clinical in a period of the last 24 years • Sample: 191 Older adults of both sexes with oncological disease and 54 criteria that are terminally attended the Department of Oncology in the period of 24 years RESULTS: • The epidemiological characteristics of 191 elderly Less than half are predominantly male young seniors and the type of cancer most frequent pathology was i lung cancer, colon cancer, stomach cancer and unknown primary. More than half are female predominance of young and elderly oncological pathology type was most frequent cancer breast, colon, ovarian and lymphoma cancer • Less than half of older men terminalidad presented some criteria, being among the most frequent esophageal cancer with lung metastases of prostate cancer

  14. CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer-Specific Death, and Increased Risk of a Second Breast Cancer

    DEFF Research Database (Denmark)

    Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul; Bolla, Manjeet K; Nevanlinna, Heli; Van't Veer, Laura J; Garcia-Closas, Montserrat; Hopper, John L; Hall, Per; Andrulis, Irene L; Devilee, Peter; Fasching, Peter A; Anton-Culver, Hoda; Lambrechts, Diether; Hooning, Maartje; Cox, Angela; Giles, Graham G; Burwinkel, Barbara; Lindblom, Annika; Couch, Fergus J; Mannermaa, Arto; Grenaker Alnæs, Grethe; John, Esther M; Dörk, Thilo; Flyger, Henrik; Dunning, Alison M; Wang, Qin; Muranen, Taru A; van Hien, Richard; Figueroa, Jonine; Southey, Melissa C; Czene, Kamila; Knight, Julia A; Tollenaar, Rob A E M; Beckmann, Matthias W; Ziogas, Argyrios; Christiaens, Marie-Rose; Collée, Johanna Margriet; Reed, Malcolm W R; Severi, Gianluca; Marme, Frederik; Margolin, Sara; Olson, Janet E; Kosma, Veli-Matti; Kristensen, Vessela N; Miron, Alexander; Bogdanova, Natalia; Shah, Mitul; Blomqvist, Carl; Broeks, Annegien; Sherman, Mark; Phillips, Kelly-Anne; Li, Jingmei; Liu, Jianjun; Glendon, Gord; Seynaeve, Caroline; Ekici, Arif B; Leunen, Karin; Kriege, Mieke; Cross, Simon S; Baglietto, Laura; Sohn, Christof; Wang, Xianshu; Kataja, Vesa; Børresen-Dale, Anne-Lise; Meyer, Andreas; Easton, Douglas F; Schmidt, Marjanka K; Bojesen, Stig E

    2012-01-01

    PURPOSE We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. PATIENTS AND METHODS From 22 studies participating in the Breast Cancer...... Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast...... cancer in prospective studies. Results CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death...

  15. (-)-Oleocanthal rapidly and selectively induces cancer cell death via lysosomal membrane permeabilization

    Science.gov (United States)

    LeGendre, Onica; Breslin, Paul AS; Foster, David A

    2015-01-01

    (-)-Oleocanthal (OC), a phenolic compound present in extra-virgin olive oil (EVOO), has been implicated in the health benefits associated with diets rich in EVOO. We investigated the effect of OC on human cancer cell lines in culture and found that OC induced cell death in all cancer cells examined as rapidly as 30 minutes after treatment in the absence of serum. OC treatment of non-transformed cells suppressed their proliferation but did not cause cell death. OC induced both primary necrotic and apoptotic cell death via induction of lysosomal membrane permeabilization (LMP). We provide evidence that OC promotes LMP by inhibiting acid sphingomyelinase (ASM) activity, which destabilizes the interaction between proteins required for lysosomal membrane stability. The data presented here indicate that cancer cells, which tend to have fragile lysosomal membranes compared to non-cancerous cells, are susceptible to cell death induced by lysosomotropic agents. Therefore, targeting lysosomal membrane stability represents a novel approach for the induction of cancer-specific cell death. PMID:26380379

  16. Death rate due to horseshoe crab poisoning: summarization on Thai reports

    OpenAIRE

    Beuy Joob; Viroj Wiwanitkit

    2015-01-01

    Horseshoe crab can be poisonous and intoxication due to intake of horseshoe crab is possible. Horseshoe crab intoxication can be seen in many countries with seacoasts including Thailand. Here, the authors summarized the death rate due to horseshoe crab poisoning in Thailand.

  17. The Combined Effect of Individual and Neighborhood Socioeconomic Status on Cancer Survival Rates

    OpenAIRE

    Chang, Chun-Ming; Su, Yu-Chieh; Lai, Ning-Sheng; Huang, Kuang-Yung; Chien, Sou-Hsin; Chang, Yu-Han; Lian, Wei-Cheng; Hsu, Ta-Wen; Lee, Ching-Chih

    2012-01-01

    Background This population-based study investigated the relationship between individual and neighborhood socioeconomic status (SES) and mortality rates for major cancers in Taiwan. Methods A population-based follow-up study was conducted with 20,488 cancer patients diagnosed in 2002. Each patient was traced to death or for 5 years. The individual income-related insurance payment amount was used as a proxy measure of individual SES for patients. Neighborhood SES was defined by income, and neig...

  18. Facing death : physicians' difficulties and coping strategies in cancer care

    OpenAIRE

    Andræ, Margareta

    1994-01-01

    Even if the treatment of cancer has developed over the last decades 50% of the patients still die of their cancer. The doctor's way of dealing with his and his patient's anxiety must surely be of significance for the treatment the patient receives. In the first part of the thesis earlier studies of physicians' stress and ways of coping are reported. There is a lack of systematic studies which show how doctors working with cancer patients adjust to this work. The aim of this investigation is t...

  19. Death rates from diabetes mellitus in Ireland 1833—1983: a historical commentary

    OpenAIRE

    Crawford, E M

    1987-01-01

    A world-wide increase in diabetic deaths and a varying rate of increase between one country and another over the past hundred years has long been recognised. During the nineteenth century, the incidence of diabetes was low in Ireland as measured by mortality. Nevertheless, the rising trend found elsewhere was also apparent in Ireland. Recorded deaths were 0.22/100,000 of the population in 1840, rising to 13.2 by 1972. Most of the increase occurred between the 1880s and 1911, but only 15% of t...

  20. Peer Relationships of Bereaved Siblings and Comparison Classmates After a Child's Death from Cancer*

    OpenAIRE

    Gerhardt, Cynthia A.; Fairclough, Diane L.; Grossenbacher, Julie C.; Barrera, Maru; Jo Gilmer, Mary; Foster, Terrah L.; Compas, Bruce E.; Davies, Betty; Hogan, Nancy S.; Vannatta, Kathryn

    2011-01-01

    Objectives To compare peer relationships among bereaved siblings and matched classmates, and to examine gender, grade level, and time since death as moderators. Methods Families were recruited from cancer registries at four hospitals 3–12 months after a child's death. Measures of social behavior and peer acceptance were completed by children in the classrooms of 105 bereaved siblings (ages 8 –17 years). Teachers also reported on children's social behavior. Three classmates were matched for ge...

  1. Risk factors for cancer recurrence or death within 6 months after liver resection in patients with colorectal cancer liver metastasis

    OpenAIRE

    Jung, Sung Won; Kim, Dong-Sik; Yu, Young Dong; Han, Jae hyun; Suh, Sung-Ock

    2016-01-01

    Purpose The aim of this study was to find risk factors for early recurrence (ER) and early death (ED) after liver resection for colorectal cancer liver metastasis (CRCLM). Methods Between May 1990 and December 2011, 279 patients underwent liver resection for CRCLM at Korea University Medical Center. They were assigned to group ER (recurrence within 6 months after liver resection) or group NER (non-ER; no recurrence within 6 months after liver resection) and group ED (death within 6 months aft...

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

    International Nuclear Information System (INIS)

    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

  3. Anti cancer effects of curcumin: cycle of life and death

    Directory of Open Access Journals (Sweden)

    Das Tanya

    2008-10-01

    Full Text Available Abstract Increasing knowledge on the cell cycle deregulations in cancers has promoted the introduction of phytochemicals, which can either modulate signaling pathways leading to cell cycle regulation or directly alter cell cycle regulatory molecules, in cancer therapy. Most human malignancies are driven by chromosomal translocations or other genetic alterations that directly affect the function of critical cell cycle proteins such as cyclins as well as tumor suppressors, e.g., p53. In this respect, cell cycle regulation and its modulation by curcumin are gaining widespread attention in recent years. Extensive research has addressed the chemotherapeutic potential of curcumin (diferuloylmethane, a relatively non-toxic plant derived polyphenol. The mechanisms implicated are diverse and appear to involve a combination of cell signaling pathways at multiple levels. In the present review we discuss how alterations in the cell cycle control contribute to the malignant transformation and provide an overview of how curcumin targets cell cycle regulatory molecules to assert anti-proliferative and/or apoptotic effects in cancer cells. The purpose of the current article is to present an appraisal of the current level of knowledge regarding the potential of curcumin as an agent for the chemoprevention of cancer via an understanding of its mechanism of action at the level of cell cycle regulation. Taken together, this review seeks to summarize the unique properties of curcumin that may be exploited for successful clinical cancer prevention.

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

    OpenAIRE

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

    2015-01-01

    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...

  5. Role of p53 in Cell Death and Human Cancers

    OpenAIRE

    Toshinori Ozaki; Akira Nakagawara

    2011-01-01

    p53 is a nuclear transcription factor with a pro-apoptotic function. Since over 50% of human cancers carry loss of function mutations in p53 gene, p53 has been considered to be one of the classical type tumor suppressors. Mutant p53 acts as the dominant-negative inhibitor toward wild-type p53. Indeed, mutant p53 has an oncogenic potential. In some cases, malignant cancer cells bearing p53 mutations display a chemo-resistant phenotype. In response to a variety of cellular stresses such as DNA ...

  6. Mortality rate of gastric cancer in the population of Belgrade for 1990-2002 period

    Directory of Open Access Journals (Sweden)

    Šipetić Sandra B.

    2005-01-01

    Full Text Available Background. Worldwide, gastric cancer is the fourth leading cause of diseases, and the second leading cause of cancer deaths. Aim. To analyze the differences between men and women in mortality rate of gastric cancer in Belgrade from 1990−2002. Methods. Mortality rates standardized directly to the „World population“, and regression analysis were used. Results. In Belgrade population, 29.2% out the total number of deaths attributable to cancer were caused by gastric cancer. Gastric cancer was the second most common cause of death among digestive tract cancers. In women, in the period between 1990 and 1993, an average annual decline of mortality was 9.0% (95% confidence interval (CI = 5.9−13.1, and between 1994 and 2002, an average annual increase was 10.3% (CI = 8.4−12.6. Mortality rate series of gastric cancer in men did not fit any of the usual trend functions. The male/female gastric cancer mortality ratio was 1.7 : 1. Mortality rates for gastric cancer rose with age in both sexes and they were highest in the age group of 70 and more years. From 1990−2002, in both sexes aged 70 years and more, mortality from gastric cancer rose by 67.2% (CI = 58.0−76.4 in men and by 69.6% (CI = 60.6−78.6 in women. During the same period, the death rates in men decreased by 75.9 % (CI = 67.5−84.4 in the age group of 30−39 years, and by 48.1% (CI = 38.4−57.9 in women aged 50−59 years. In both sexes mortality rate series of all other age groups did not fit any of the usual trend functions. Conclusions. The increase in mortality rate of gastric in women over the past few years, showed the necessity of instituting primary and secondary preventive measures.

  7. Early Parental Adjustment and Bereavement after Childhood Cancer Death

    Science.gov (United States)

    Barrera, Maru; O'connor, Kathleen; D'Agostino, Norma Mammone; Spencer, Lynlee; Nicholas, David; Jovcevska, Vesna; Tallet, Susan; Schneiderman, Gerald

    2009-01-01

    This study comprehensively explored parental bereavement and adjustment at 6 months post-loss due to childhood cancer. Interviews were conducted with 18 mothers and 13 fathers. Interviews were transcribed verbatim and analyzed based on qualitative methodology. A model describing early parental bereavement and adaptation emerged with 3 domains:…

  8. Ionizing radiation decreases human cancer mortality rates

    International Nuclear Information System (INIS)

    Information from nine studies with exposed nuclear workers and military observers of atmospheric bomb explosions confirms the results from animal studies which showed that low doses of ionizing radiation are beneficial. The usual ''healthy worker effect'' was eliminated by using carefully selected control populations. The results from 13 million person-years show the cancer mortality rate of exposed persons is only 65.6% that of carefully selected unexposed controls. This overwhelming evidence makes it politically untenable and morally wrong to withhold public health benefits of low dose irradiation. Safe supplementation of ionizing radiation should become a public health service. (author)

  9. Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality

    Directory of Open Access Journals (Sweden)

    Kravchenko J

    2014-06-01

    Full Text Available Julia Kravchenko,1 Igor Akushevich,2 Amy P Abernethy,3 Sheila Holman,4 William G Ross Jr,5 H Kim Lyerly1,6 1Department of Surgery, 2Center for Population Health and Aging, 3Duke Clinical Research Institute, Duke University Medical Center, Duke University, Durham, 4Division of Air Quality, North Carolina Department of Environment and Natural Resources, Raleigh, 5Nicholas School of the Environment, 6Department of Pathology, Duke University Medical Center, Duke University, Durham, NC, USA Background: The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. Materials and methods: We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2, nitrogen dioxide (NO2, carbon monoxide (CO, and particulate matters (PM2.5 and PM10 using monthly data measurements from air-monitoring stations in North Carolina in 1993–2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. Results: Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths–with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths–with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only

  10. Pyrvinium targets autophagy addiction to promote cancer cell death

    OpenAIRE

    Deng, Longfei; Lei, Yunlong; Liu, Rui; Li, Jingyi; Yuan, Kefei; Li, Yi; Chen, Yi; Liu, Yi; Lu, You; Edwards III, Carl K; Huang, Canhua; Wei, Yuquan

    2013-01-01

    Autophagy is a cellular catabolic process by which long-lived proteins and damaged organelles are degradated by lysosomes. Activation of autophagy is an important survival mechanism that protects cancer cells from various stresses, including anticancer agents. Recent studies indicate that pyrvinium pamoate, an FDA-approved antihelminthic drug, exhibits wide-ranging anticancer activity. Here we demonstrate that pyrvinium inhibits autophagy both in vitro and in vivo. We further demonstrate that...

  11. Cancer in Europe: Death sentence or life sentence?

    Science.gov (United States)

    Liu, Lifang; O'Donnell, Peter; Sullivan, Richard; Katalinic, Alexander; Moser, Lotte; de Boer, Angela; Meunier, Francoise

    2016-09-01

    With so many adults and children receiving successful treatment for their cancer, survivorship is now a 'new' and critical issue. It is increasingly recognised that the growing numbers of survivors face new challenges in their bid to return to 'normal' life. What is not yet so widely recognised is the need for a broad response to help them cope-with stigmatisation, misunderstanding, lifelong issues of confidence and social adaptation, and even access to employment and to financial services. As a further stage in its programme of attention to this aspect of cancer, the European Organisation for Research and Treatment of Cancer (EORTC) brought survivors, researchers, carers, authorities and policymakers together at a meeting in Brussels in March/April 2016, to learn at first hand about the posttreatment experience of cancer survivors. The meeting demonstrated that while research is well advanced in many of the medical consequences of survivorship, understanding is still lacking of many non-clinical, personal and administrative issues. The meeting raised the discussion of survivorship research beyond the individual to a population-based approach, exploring the related socioeconomic issues. Its exploration of initiatives across Europe countries provoked new thinking on the need for effective collaboration, with a new focus on non-clinical issues, including effective dialogue with financial service providers and employers, improvements in collecting, exchanging and accessing data, and above all, ways of translating research outcomes into action. This will require wider recognition that, as Françoise Meunier, Director Special Projects, EORTC, said, 'It is time for a new mind set'. PMID:27498140

  12. Role of p53 in Cell Death and Human Cancers

    International Nuclear Information System (INIS)

    p53 is a nuclear transcription factor with a pro-apoptotic function. Since over 50% of human cancers carry loss of function mutations in p53 gene, p53 has been considered to be one of the classical type tumor suppressors. Mutant p53 acts as the dominant-negative inhibitor toward wild-type p53. Indeed, mutant p53 has an oncogenic potential. In some cases, malignant cancer cells bearing p53 mutations display a chemo-resistant phenotype. In response to a variety of cellular stresses such as DNA damage, p53 is induced to accumulate in cell nucleus to exert its pro-apoptotic function. Activated p53 promotes cell cycle arrest to allow DNA repair and/or apoptosis to prevent the propagation of cells with serious DNA damage through the transactivation of its target genes implicated in the induction of cell cycle arrest and/or apoptosis. Thus, the DNA-binding activity of p53 is tightly linked to its tumor suppressive function. In the present review article, we describe the regulatory mechanisms of p53 and also p53-mediated therapeutic strategies to cure malignant cancers

  13. 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. PMID:26054380

  14. 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.

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

    Science.gov (United States)

    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…

  16. Clinical Dementia Rating Performed Several Years prior to Death Predicts Regional Alzheimer’s Neuropathology

    Science.gov (United States)

    Beeri, Michal Schnaider; Silverman, Jeremy M.; Schmeidler, James; Wysocki, Michael; Grossman, Hillel Z.; Purohit, Dushyant P.; Perl, Daniel P.; Haroutunian, Vahram

    2011-01-01

    Aims To assess the relationships between early and late antemortem measures of dementia severity and Alzheimer disease (AD) neuropathology severity. Methods 40 residents of a nursing home, average age at death 82.0, participated in this longitudinal cohort study with postmortem assessment. Severity of dementia was measured by Clinical Dementia Rating (CDR) at two time points, averaging 4.5 and 1.0 years before death. Densities of postmortem neuritic plaques (NPs) and neurofibrillary tangles (NFTs) were measured in the cerebral cortex, hippocampus, and entorhinal cortex. Results For most brain areas, both early and late CDRs were significantly associated with NPs and NFTs. CDRs assessed proximal to death predicted NFTs beyond the contribution of early CDRs. NPs were predicted by both early and late CDRs. NPs were predictive of both early and late CDRs after controlling for NFTs. NFTs were only associated significantly with late CDR in the cerebral cortex after controlling for NPs. Conclusions Even if assessed several years before death, dementia severity is associated with AD neuropathology. NPs are more strongly associated with dementia severity than NFTs. NFTs consistently associate better with late than early CDR, suggesting that these neuropathological changes may occur relatively later in the course of the disease. PMID:18367838

  17. The suitability of using death certificates as a data source for cancer mortality assessement in Turkey

    OpenAIRE

    Ulus, Tumer; Yurtseven, Eray; Cavdar, Sabanur; Erginoz, Ethem; Erdogan, M. Sarper

    2012-01-01

    Aim To compare the quality of the 2008 cancer mortality data of the Istanbul Directorate of Cemeteries (IDC) with the 2008 data of International Agency for Research on Cancer (IARC) and Turkish Statistical Institute (TUIK), and discuss the suitability of using this databank for estimations of cancer mortality in the future. Methods We used 2008 and 2010 death records of the IDC and compared it to TUIK and IARC data. Results According to the WHO statistics, in Turkey in 2008 there were 67 255 ...

  18. PRESSING MORTALITY RATE THROUGH SCREENING oral cancer

    Directory of Open Access Journals (Sweden)

    L. K. Widnyani Wulan Laksmi

    2013-09-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Based on World Health Organization (WHO data, oral cancer is one of malignancy with the highest mortality. In USA, there are more than 30.000 new cases every year. We can find many risk factors of oral cancer in our daily living. Moreover, it’s easy to find the main risk factors in our society, they are smoking, alcohol consumption, tobacco consumtion, viral infection, and bad oral hygiene. For the early stadium, Five-years survival rate is about 82% and 61% for all stadium. But, more than 50% of oral cancer has been distributed (metastatic regionally and also into the other organ far away from the oral itself when it’s detected. It will decrease 5-years survival rate to be less than 50%. So that, it’s really important to detect the oral cancer at the earlier stadium. Screening is the way to find the earlier stadium. Screening is done by some methods, start from the anamnesis, physical examination, toluidine blue staining, endoscopy, cytology, telomerase examination, and also PET-scan if it’s possible (because of the financial reasons. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  19. The combined effect of individual and neighborhood socioeconomic status on cancer survival rates.

    Directory of Open Access Journals (Sweden)

    Chun-Ming Chang

    Full Text Available BACKGROUND: This population-based study investigated the relationship between individual and neighborhood socioeconomic status (SES and mortality rates for major cancers in Taiwan. METHODS: A population-based follow-up study was conducted with 20,488 cancer patients diagnosed in 2002. Each patient was traced to death or for 5 years. The individual income-related insurance payment amount was used as a proxy measure of individual SES for patients. Neighborhood SES was defined by income, and neighborhoods were grouped as living in advantaged or disadvantaged areas. The Cox proportional hazards model was used to compare the death-free survival rates between the different SES groups after adjusting for possible confounding and risk factors. RESULTS: After adjusting for patient characteristics (age, gender, Charlson Comorbidity Index Score, urbanization, and area of residence, tumor extent, treatment modalities (operation and adjuvant therapy, and hospital characteristics (ownership and teaching level, colorectal cancer, and head and neck cancer patients under 65 years old with low individual SES in disadvantaged neighborhoods conferred a 1.5 to 2-fold higher risk of mortality, compared with patients with high individual SES in advantaged neighborhoods. A cross-level interaction effect was found in lung cancer and breast cancer. Lung cancer and breast cancer patients less than 65 years old with low SES in advantaged neighborhoods carried the highest risk of mortality. Prostate cancer patients aged 65 and above with low SES in disadvantaged neighborhoods incurred the highest risk of mortality. There was no association between SES and mortality for cervical cancer and pancreatic cancer. CONCLUSIONS: Our findings indicate that cancer patients with low individual SES have the highest risk of mortality even under a universal health-care system. Public health strategies and welfare policies must continue to focus on this vulnerable group.

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

    Science.gov (United States)

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

    2014-08-01

    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. PMID:25097749

  1. Centenarian Rates and Life Expectancy Related to the Death Rates of Multiple Sclerosis, Asthma, and Rheumatoid Arthritis and the Incidence of Type 1 Diabetes in Children.

    Science.gov (United States)

    Lens-Pechakova, Lilia S

    2016-02-01

    The autoimmune diseases are among the 10 leading causes of death for women and the number two cause of chronic illness in America as well as a predisposing factor for cardiovascular diseases and cancer. Patients of some autoimmune diseases have shown a shorter life span and are a model of accelerated immunosenescence. Conversely, centenarians are used as a model of successful aging and have shown several immune parameters that are better preserved and lower levels of autoantibodies. The study reported here focused on clarifying the connection between longevity and some autoimmune and allergic diseases in 29 developed Organisation for Economic Co-operation and Development (OECD) countries, because multidisciplinary analyses of the accelerated or delayed aging data could show a distinct relationship pattern, help to identify common factors, and determine new important factors that contribute to longevity and healthy aging. The relationships between the mortality rates data of multiple sclerosis (MS), rheumatoid arthritis (RA), asthma, the incidence of type 1 diabetes (T1D) from one side and centenarian rates (two sets) as well as life expectancy data from the other side were assessed using regression models and Pearson correlation coefficients. The data obtained correspond to an inverse linear correlation with different degrees of linearity. This is the first observation of a clear tendency of diminishing centenarian rates or life expectancy in countries having higher death rates of asthma, MS, and RA and a higher incidence of T1D in children. The conclusion is that most probably there are common mechanistic pathways and factors affecting the above diseases and at the same time but in the opposite direction the processes of longevity. Further study, comparing genetic data, mechanistic pathways, and other factors connected to autoimmune diseases with those of longevity could clarify the processes involved, so as to promote longevity and limit the expansion of those

  2. Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Gyrd-Hansen, Mads; Lykkesfeldt, Anne E; Issinger, Olaf-Georg; Stenvang, Jan

    2007-01-01

    future breast cancer treatment. In this study, we have investigated the effect of the chemotherapeutic compound cisplatin using a panel of antiestrogen-resistant breast cancer cell lines established from the human breast cancer cell line MCF-7. We show that the antiestrogen-resistant cells are...... parental MCF-7 cells. Our data show that Bcl-2 can protect antiestrogen-resistant breast cancer cells from cisplatin-induced cell death, indicating that the reduced expression of Bcl-2 in the antiestrogen-resistant cells plays a role in sensitizing the cells to cisplatin treatment.......Antiestrogens are currently used for treating breast cancer patients who have estrogen receptor-positive tumors. However, patients with advanced disease will eventually develop resistance to the drugs. Therefore, compounds effective on antiestrogen-resistant tumors will be of great importance for...

  3. Lung cancer: district active treatment rates affect survival

    OpenAIRE

    CARTMAN, M.; Hatfield, A; Muers, M; Peake, M; Haward, R; Forman, D

    2002-01-01

    Design: A retrospective study of population based data held by the Northern & Yorkshire Cancer Registry and Information Service (NYCRIS), comparing active treatment rates for lung cancer with survival by districts.

  4. Microscopic analysis of cell death by metabolic stress-induced autophagy in prostate cancer

    Science.gov (United States)

    Changou, Chun; Cheng, R. Holland; Bold, Richard; Kung, Hsing-Jien; Chuang, Frank Y. S.

    2013-02-01

    Autophagy is an intracellular recycling mechanism that helps cells to survive against environmental stress and nutritional starvation. We have recently shown that prostate cancers undergo metabolic stress and caspase-independent cell death following exposure to arginine deiminase (ADI, an enzyme that degrades arginine in tissue). The aims of our current investigation into the application of ADI as a novel cancer therapy are to identify the components mediating tumor cell death, and to determine the role of autophagy (stimulated by ADI and/or rapamycin) on cell death. Using advanced fluorescence microscopy techniques including 3D deconvolution and superresolution structured-illumination microscopy (SIM), we show that prostate tumor cells that are killed after exposure to ADI for extended periods, exhibit a morphology that is distinct from caspase-dependent apoptosis; and that autophagosomes forming as a result of ADI stimulation contain DAPI-stained nuclear material. Fluorescence imaging (as well as cryo-electron microscopy) show a breakdown of both the inner and outer nuclear membranes at the interface between the cell nucleus and aggregated autophagolysosomes. Finally, the addition of N-acetyl cysteine (or NAC, a scavenger for reactive oxygen species) effectively abolishes the appearance of autophagolysosomes containing nuclear material. We hope to continue this research to understand the processes that govern the survival or death of these tumor cells, in order to develop methods to improve the efficacy of cancer pharmacotherapy.

  5. AB158. Atorvastatin induces autophagic cell death in prostate cancer cells in vitro

    Science.gov (United States)

    He, Zhenhua; Wang, Zhiping

    2016-01-01

    Objective Although it is well known that apoptosis contributes to cancer cell death, the role of autophagy in cancer cell death has remained in dispute. Atorvastatin has been suggested to exhibit anti-cancer effects. The present study aimed to examine atorvastatin-induced autophagy-associated cell death and the autophagy-associated gene expression profile in the PC3 prostate carcinoma cell line. Methods The atorvastatin-induced process of autophagy in PC3 cells was determined via evaluation of the cellular expression levels of autophagosomal marker light-chain-3 (LC3)-II, using immunoblotting and counting of green fluorescent protein (GFP)-LC3-transfected autophagiccells. Apoptosis was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and an MTT assay was used to evaluate cell viability. Total RNA of PC3 cells was isolated for characterization of the gene expression profile following atorvastatin treatment. Results Atorvastatin treatment of PC3 cells for 24 h increased the expression of GFP-LC3-II by >25% and expression continued for >72 h, while apoptosis was not significantly induced within this time period. Four genes associated with the autophagy machinery were also significantly upregulated. Conclusions In the presence of atorvastatin, autophagy may be unable to abrogate cell damage and may therefore contribute to cellular dysfunction, leading to autophagic/type II programmed cell death. In response to atorvastatin treatment, the expression of genes involved in autophagic mediating pathways may have a role in tumor suppression.

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

    International Nuclear Information System (INIS)

    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

  7. Breast Cancer Disparities

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  8. Estimation of rates of births, deaths, and immigration from mark-recapture data.

    Science.gov (United States)

    O'Hara, R B; Lampila, S; Orell, M

    2009-03-01

    The analysis of mark-recapture data is undergoing a period of development and expansion. Here we contribute to that by presenting a model which includes both births and immigration, as well as the usual deaths. Data come from a long-term study of the willow tit (Parus montanus), where we can assume that all births are recorded, and hence immigrants can also be identified as birds captured as adults for the first time. We model the rates of immigration, birth rate per parent, and death rates of juveniles and adults. Using a hierarchical model allows us to incorporate annual variation in these parameters. The model is fitted to the data using Markov chain Monte Carlo, as a Bayesian analysis. In addition to the model fitting, we also check several aspects of the model fit, in particular whether survival varies with age or immigrant status, and whether capture probability is affected by previous capture history. The latter check is important, as independence of capture histories is a key assumption that simplifies the model considerably. Here we find that the capture probability depends strongly on whether the individual was captured in the previous year. PMID:18479483

  9. A Nonseparable Multivariate Space-Time Model for Analyzing County-Level Heart Disease Death Rates by Race and Gender

    OpenAIRE

    Quick, Harrison; Waller, Lance A.; Casper, Michele

    2015-01-01

    While death rates due to diseases of the heart have experienced a sharp decline over the past 50 years, these diseases continue to be the leading cause of death in the United States, and the rate of decline varies by geographic location, race, and gender. We look to harness the power of hierarchical Bayesian methods to obtain a clearer picture of the declines from county-level, temporally varying heart disease death rates for men and women of different races in the US. Specifically, we propos...

  10. CD4 decline is associated with increased risk of cardiovascular disease, cancer, and death in virally suppressed patients with HIV

    DEFF Research Database (Denmark)

    Helleberg, Marie; Kronborg, Gitte; Larsen, Carsten S; Pedersen, Gitte; Pedersen, Court; Obel, Niels; Gerstoft, Jan

    2013-01-01

    immunodeficiency virus (HIV) were followed in the Danish nationwide, population-based cohort study in the period 1995-2010 with quarterly CD4 measurements. Associations between a CD4 decline of ≥30% and cardiovascular disease, cancer, and death were analyzed using Poisson regression with date of CD4 decline as a...... time-updated variable. Results. We followed 2584 virally suppressed HIV patients for 13 369 person-years (PY; median observation time, 4.7 years). Fifty-six patients developed CD4 decline (incidence rate, 4.2/1000 PY [95% confidence interval {CI}, 3.2-5.4]). CD4 counts dropped from a median of 492...... cells/µL to 240 cells/µL. CD8, CD3, and total lymphocyte counts dropped concomitantly. No HIV-related factors, apart from treatment with didanosine, were associated with CD4 decline. The risk of cardiovascular disease, cancer, and death increased markedly ≤6 months after CD4 decline (incidence rate...

  11. Differences in late fetal death rates in association with determinants of small for gestational age fetuses: population based cohort study

    Science.gov (United States)

    Cnattingius, Sven; Haglund, Bengt; Kramer, Michael S

    1998-01-01

    Objective: To examine differences in late fetal death rates in association with determinants of small for gestational age fetuses. Design: Population based cohort study. Subjects: 1 026 249 pregnancies without congenital malformations. Setting: Sweden 1983-92. Main outcome measure: Late fetal death rate. Results: Depending on underlying determinants late fetal death rates were greatly increased in extremely small for gestational age fetuses (range 16 to 45 per 1000) compared with non-small for gestational age fetuses (1.4 to 4.6). In extremely small for gestational age fetuses late fetal death rates were increased from 31 per 1000 in mothers aged less than 35 years to 45 per 1000 in older mothers, and from 22 per 1000 in women <155 cm in height to 33 per 1000 in women ⩾175 cm tall. Late fetal death rates were also higher in extremely small for gestational age fetuses in singleton compared with twin pregnancies and in non-hypertensive pregnancies compared with pregnancies complicated by severe pre-eclampsia or other hypertensive disorders. Slightly higher late fetal death rates were observed in nulliparous compared with parous women and in non-smokers compared with smokers. Conclusions: Although the risk of late fetal death is greatly increased in fetuses that are extremely small for gestational age the risk is strongly modified by underlying determinants—for example, there is a lower risk of late fetal death in a small for gestational age fetus if the mother is of short stature, has a twin pregnancy, or has hypertension. Key messages Small for gestational age fetuses are at increased risk of late fetal death regardless of the underlying determinants The effect of birthweight ratio on risk of late fetal death is modified by underlying determinants, except maternal age Regardless of birthweight ratio the rates of late fetal death are higher among women aged 35 years or older compared with younger women In pregnancies of extremely small for gestational age

  12. Apoptotic death of prostate cancer cells by a gonadotropin-releasing hormone-II antagonist.

    Directory of Open Access Journals (Sweden)

    Sumi Park

    Full Text Available Gonadotropin-releasing hormone-I (GnRH-I has attracted strong attention as a hormonal therapeutic tool, particularly for androgen-dependent prostate cancer patients. However, the androgen-independency of the cancer in advanced stages has spurred researchers to look for new medical treatments. In previous reports, we developed the GnRH-II antagonist Trp-1 to inhibit proliferation and stimulate the autophagic death of various prostate cancer cells, including androgen-independent cells. We further screened many GnRH-II antagonists to identify molecules with higher efficiency. Here, we investigated the effect of SN09-2 on the growth of PC3 prostate cancer cells. SN09-2 reduced the growth of prostate cancer cells but had no effect on cells derived from other tissues. Compared with Trp-1, SN09-2 conspicuously inhibited prostate cancer cell growth, even at low concentrations. SN09-2-induced PC3 cell growth inhibition was associated with decreased membrane potential in mitochondria where the antagonist was accumulated, and increased mitochondrial and cytosolic reactive oxygen species. SN09-2 induced lactate dehydrogenase release into the media and annexin V-staining on the PC3 cell surface, suggesting that the antagonist stimulated prostate cancer cell death by activating apoptotic signaling pathways. Furthermore, cytochrome c release from mitochondria to the cytosol and caspase-3 activation occurred in a concentration- and time-dependent manner. SN09-2 also inhibited the growth of PC3 cells xenotransplanted into nude mice. These results demonstrate that SN09-2 directly induces mitochondrial dysfunction and the consequent ROS generation, leading to not only growth inhibition but also apoptosis of prostate cancer cells.

  13. Immunologic checkpoints in cancer therapy: focus on the programmed death-1 (PD-1 receptor pathway

    Directory of Open Access Journals (Sweden)

    Momtaz P

    2014-11-01

    Full Text Available Parisa Momtaz,1,2 Michael A Postow1,2 1Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Weill Cornell Medical College, New York, NY, USA Abstract: T-lymphocytes have the potential to recognize cancer antigens as foreign and therefore eliminate them. However, immune checkpoints such as cytotoxic T-lymphocyte-associated antigen (CTLA-4 and programmed cell death (PD-1 receptor and its ligands (PD-L1, PD-L2 suppress the activity of T-lymphocytes. Advances in the understanding of immunology and its role in cancer have led to the development of immune checkpoint inhibitors that block CTLA-4 and PD-1 and result in durable responses in patients with a wide range of cancers. PD-1 and PD-L1 inhibitors are currently in many stages of clinical investigation, and the anti-PD-1 antibody, pembrolizumab, was recently approved by the US Food and Drug Administration. Many questions remain to be answered, such as the optimal administration schedule, biomarkers that associate with benefit, and potential for use of PD-1 agents in combination approaches. Nonetheless, immunotherapy with PD-1 blocking antibodies is now becoming an integral part in the management of cancer. Keyword: immune checkpoints, immunotherapy, programmed cell death protein-1, cytotoxic T-lymphocyte antigen 4

  14. Comparison of Continuing Bonds Reported by Parents and Siblings After a Child's Death from Cancer

    OpenAIRE

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

    2011-01-01

    Few studies have distinguished similarities and differences between continuing bonds as they appear in various bereaved populations, particularly parent versus sibling cohorts following a child's death. This mixed-method study compared how parents and siblings experienced continuing bonds in 40 families who lost a child to cancer. Thirty-six mothers, 24 fathers, and 39 siblings were recruited 3-12 months post-loss (M = 10.7, SD = 3.5). Nearly all participants (97%) reported engaging in purpos...

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

    Directory of Open Access Journals (Sweden)

    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

  16. The expression status and prognostic significance of programmed cell death 1 ligand 1 in gastrointestinal tract cancer: a systematic review and meta-analysis

    OpenAIRE

    Huang, Baohua; Chen, Lei; Bao, Cuixia; Sun, Chengming; Jie LI; Wang, Lipeng; Zhang, Xia

    2015-01-01

    Background Programmed cell death 1 ligand 1 (PD-L1) expression has been observed in various malignancies. However, the association between PD-L1 expression and the survival of patients with gastrointestinal tract cancer remains controversial. Besides, the rate of PD-L1 positivity on tumor cells of digestive tract cancer is not clear. Thus, we performed a meta-analysis by incorporating all available evidence to evaluate the rate of PD-L1 positivity and the overall survival (OS) according to PD...

  17. Negative influence of programmed death-1-ligands on the survival of esophageal cancer patients treated with chemotherapy.

    Science.gov (United States)

    Tanaka, Koji; Miyata, Hiroshi; Sugimura, Keijiro; Kanemura, Takashi; Hamada-Uematsu, Mika; Mizote, Yu; Yamasaki, Makoto; Wada, Hisashi; Nakajima, Kiyokazu; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro; Tahara, Hideaki

    2016-06-01

    The programmed death-1/programmed death-1 ligands (PD-1/PD-L) pathway plays an important role in immunological tumor evasion. However, the clinical significance of the PD-L (L1 and L2) expression in esophageal cancer treated with chemotherapy has not been fully investigated. We examined the expression of PD-L of the primary tumors obtained from 180 esophageal cancer patients who underwent radical resection with or without neoadjuvant chemotherapy (NAC) using immunohistochemical staining. The relationship between the expression patterns and clinico-pathological characteristics was examined. In the present study, 53 patients (29.4%) and 88 patients (48.3%) were classified into positive for PD-L1 and PD-L2 expression, respectively. In all the patients examined, overall survival rates of the patients with tumors positive for PD-L1 or PD-L2 were significantly worse than those with tumors negative for PD-L1 or PD-L2 (P = 0.0010 and P = 0.0237, respectively). However, subgroup analysis showed that these tendencies are only found in the patients treated with NAC, and not in those without NAC. The patients with positive PD-L1 expression had a significantly higher rate of NAC history (P = 0.0139), but those with positive PD-L2 expression did not have a significantly high rate of NAC history (P = 0.6127). There is no significant relationship between PD-L1 expression and response to chemotherapy (P = 0.3118), but patients with positive PD-L2 expression had significantly inferior responses to chemotherapy (P = 0.0034). The PD-1/PD-L pathway might be an immunological mechanism associated with the long-term effectiveness of chemotherapy in esophageal cancer patients. Further investigation into the roles of PD-1 pathway in chemotherapy could lead to the development of better treatment options for this disease. PMID:27015293

  18. Effect of marital status on death rates. Part 2: Transient mortality spikes

    CERN Document Server

    Richmond, Peter

    2015-01-01

    We examine what happens in a population when it experiences an abrupt change in surrounding conditions. Several cases of such "abrupt transitions" for both physical and living social systems are analyzed from which it can be seen that all share a common pattern. First, a steep rising death rate followed by a much slower relaxation process during which the death rate decreases as a power law (with an exponent close to 0.7). This leads us to propose a general principle which can be summarized as follows: "ANY abrupt change in living conditions generates a mortality spike which acts as a kind of selection process." This we term the Transient Shock conjecture. It provides a qualitative model which leads to testable predictions. For example, marriage certainly brings about a major change in environmental and social conditions and according to our conjecture one would expect a mortality spike in the months following marriage. At first sight this may seem an unlikely proposition but we demonstrate (by three differen...

  19. Effect of marital status on death rates. Part 2: Transient mortality spikes

    Science.gov (United States)

    Richmond, Peter; Roehner, Bertrand M.

    2016-05-01

    We examine what happens in a population when it experiences an abrupt change in surrounding conditions. Several cases of such "abrupt transitions" for both physical and living social systems are analyzed from which it can be seen that all share a common pattern. First, a steep rising death rate followed by a much slower relaxation process during which the death rate decreases as a power law. This leads us to propose a general principle which can be summarized as follows: "Any abrupt change in living conditions generates a mortality spike which acts as a kind of selection process". This we term the Transient Shock conjecture. It provides a qualitative model which leads to testable predictions. For example, marriage certainly brings about a major change in personal and social conditions and according to our conjecture one would expect a mortality spike in the months following marriage. At first sight this may seem an unlikely proposition but we demonstrate (by three different methods) that even here the existence of mortality spikes is supported by solid empirical evidence.

  20. Air Temperature and Death Rates in the Continental U.S., 1968–2013

    Directory of Open Access Journals (Sweden)

    John Hart

    2015-06-01

    Full Text Available A previous test of global warming theory, on a local level, for Texas revealed inverse correlations between air temperature and death rates. The present study expands the test field to the continental U.S. Using an ecological design, mean daily maximum air temperature (“temperature” in the 48 contiguous states plus the District of Columbia by year from 1968–2013 was compared to age-adjusted all-cause mortality (“deaths” in these same jurisdictions for the same years using Pearson correlation (n = 46 years. The comparison was made for three race categories, white, black, and all races, where each category included all ages and both genders. There was 5.0 degree F range for the years studied (62.7–67.7 degrees F. Correlations were moderate strength, inverse, and statistically significant, as follows. Whites: r = −0.576, p < 0.0001; Blacks: r = −0.556, p = 0.0001; and all races: r = −0.577, p < 0.0001. These correlations are consistent with the Texas study, both of which indicated that warmer years tended to correlate with decreased death rates. A limitation to this research is its (ecological design, but is an initial step towards further investigation.

  1. Widening educational disparities in premature death rates in twenty six states in the United States, 1993-2007.

    Directory of Open Access Journals (Sweden)

    Jiemin Ma

    Full Text Available BACKGROUND: Eliminating socioeconomic disparities in health is an overarching goal of the U.S. Healthy People decennial initiatives. We present recent trends in mortality by education among working-aged populations. METHODS AND FINDINGS: Age-standardized death rates and their average annual percent change for all-cause and five major causes (cancer, heart disease, stroke, diabetes, and accidents were calculated from 1993 through 2007 for individuals aged 25-64 years by educational attainment as a marker of socioeconomic status, using national vital registration data for 26 states with consistent educational information on the death certificates. Rate ratios and rate differences were used to assess disparities (≤12 versus ≥16 years of education for 1993 through 2007. From 1993 through 2007, relative educational disparities in all-cause mortality continued to increase among working-aged men and women in the U.S., due to larger decreases of mortality rates among the most educated coupled with smaller decreases or even worsening trends in the less educated. For example, the rate ratios of all-cause mortality increased from 2.5 (95% confidence interval (CI, 2.4-2.6 in 1993 to 3.6 (95% CI, 3.5-3.7 in 2007 in men and from 1.9 (95% CI, 1.8-2.0 to 3.0 (95% CI, 2.9-3.1 in women. Generally, the rate differences (per 100,000 persons of all-cause mortality increased from 415.5 (95% CI, 399.1-431.9 in 1993 to 472.7 (95% CI, 460.2-485.2 in 2007 in men and from 165.4 (95% CI, 154.5-176.2 to 256.2 (95% CI, 248.3-264.2 in women. Disparity patterns varied largely across the five specific causes considered in this study, with the largest increases of relative disparities for accidents, especially in women. CONCLUSIONS: Relative educational differentials in mortality continued to widen among men and women despite emphasis on reducing disparities in the U.S. Healthy People decennial initiatives.

  2. Rates of TBI-related Emergency Department Visits, Hospitalizations, and Deaths — United States, 2001–2010

    Data.gov (United States)

    U.S. Department of Health & Human Services — In general, total combined rates for traumatic brain injury (TBI)-related emergency department (ED) visits, hospitalizations and deaths have increased over the past...

  3. Changes in causes of death and mortality rates among children in Greenland from 1987 - 91 to 1992 - 99

    DEFF Research Database (Denmark)

    Aaen-Larsen, Birger; Bjerregaard, Peter

    2003-01-01

    This study analysed the spontaneous trends in mortality among children in Greenland from 1987 - 91 to 1992 - 99 and describes the changes in the causes of death, mortality rates, and variation between regions.......This study analysed the spontaneous trends in mortality among children in Greenland from 1987 - 91 to 1992 - 99 and describes the changes in the causes of death, mortality rates, and variation between regions....

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

    Directory of Open Access Journals (Sweden)

    Wei Gao

    Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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 Po

  5. 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.

  6. Disparities in female breast cancer mortality rates in Brazil between 1980 and 2009

    Directory of Open Access Journals (Sweden)

    Ruffo Freitas-Junior

    2012-07-01

    Full Text Available OBJECTIVE: To describe the temporal trends in female breast cancer mortality rates in Brazil in its macro-regions and states between 1980 and 2009. METHODS: This was an ecological time-series study using data on breast cancer deaths registered in the Mortality Data System (SIM/WHO and census data on the resident population collected by the Brazilian Institute of Geography and Statistics (IBGE/WHO. Joinpoint regression analyses were used to identify the significant changes in trends and to estimate the annual percentage change (APC in mortality rates. RESULTS: Female breast cancer mortality rates in Brazil tended to stabilize from 1994 onward (APC = 0.4%. Considering the Brazilian macro-regions, the annual mortality rates decreased in the Southeast, stabilized in the South and increased in the Northeast, North, and Midwest. Only the states of Sao Paulo (APC = -1.9%, Rio Grande do Sul (APC = -0.8% and Rio de Janeiro (APC = -0.6% presented a significant decline in mortality rates. The greatest increases were found in Maranhao (APC=12%, Paraiba (APC=11.9%, and Piaui (APC=10.9%. CONCLUSION: Although there has been a trend toward stabilization in female breast cancer mortality rates in Brazil, when the mortality rate of each macro-region and state is analyzed individually, considerable inequalities are found, with rate decline or stabilization in states with higher socioeconomic levels and a substantial increase in those with lower socioeconomic levels.

  7. Baseline serum C-reactive protein and death from colorectal cancer in the NHANES III cohort.

    Science.gov (United States)

    Swede, Helen; Hajduk, Alexandra M; Sharma, Jyoti; Rawal, Shristi; Rasool, Homaira; Vella, Anthony T; Tobet, Rebecca E; Stevens, Richard G

    2014-04-15

    Several prospective studies suggest that C-reactive protein (CRP), a nonspecific serologic marker of inflammation, might be linked to risk of colorectal cancer (CRC), whereas others have reported null or protective effects. We analyzed data from 7,072 participants (50-85 years) in the U.S. National Health and Nutrition Examination Survey III (1988-1994), a nationally representative cohort (n = 33,994; 2 months-85 years) with vital status follow-up to 2000. Hazard ratios (HRs) for mortality associated with baseline clinically raised (≥1.00 mg/dL) and intermediate (≥0.22-0.99 mg/dL) CRP levels were estimated using Cox proportional hazards regression controlling for CRC risk factors. There were 59 deaths from CRC, 106 from other obesity-related cancers (other-ORCs) and 1,130 from cardiovascular disease (CVD). Participants with clinically raised CRP at baseline were found to have a statistically significant greater risk of CRC death (HRs = 2.36-2.47) in comparison to persons with undetected levels. HRs were lower for death from other-ORC and CVD (1.82, 95% CI 1.05-3.15; 1.53, 95% CI 1.29-1.81, respectively). Intermediate CRP level was associated with a nonsignificant 10-21% increased risk for CRC death. HR for CRC death was higher among persons with a normal BMI (2.16, 95% 0.96-4.87, p = 0.06) compared to those who were overweight (1.22, 95% CI 0.53-2.78) or obese (1.23, 95% CI, 0.37-4.08). A similar pattern was observed for waist circumference. This effect modification suggests that the impact of chronic inflammation may be independent of excess body fat. Future research is recommended to confirm emerging data that elevated serologic CRP might reflect underlying colonic inflammation. PMID:24122448

  8. Heart Rate Variability as a Predictor of Death in Burn Patients.

    Science.gov (United States)

    Loguidice, Michael J; Schutt, Robert C; Horton, Jureta W; Minei, Joseph P; Keeley, Ellen C

    2016-01-01

    Heart rate variability (HRV), a noninvasive technique used to quantify fluctuations in the interval between normal heart beats (NN), is a predictor of mortality in some patient groups. The aim of this study was to assess HRV in burn trauma patients as a predictor of mortality. The authors prospectively performed 24-hour Holter monitoring on burn patients and collected demographic information, burn injury details, and in-hospital clinical events. Analysis of HRV in the time and frequency domains was performed. A total of 40 burn patients with a mean age of 44 ± 15 years were enrolled. Mean %TBSA burn was 27 ± 22% for the overall population and was significantly higher in those who died compared with those who survived (55 ± 23% vs 19 ± 13%; P < .0001). There was a statistically significant inverse linear correlation between SD of NN intervals and %TBSA (r = -.337, R = 0.113, 95% CI = -0.587 to -0.028, two-tailed P = .034), as well as with ultra low frequency power and %TBSA burn (r = -0.351, R = 0.123, 95% CI = -0.152 to -0.009; P = .027). The receiver-operator characteristic showed the area under the curve for %TBSA as a predictor of death was 0.82 (P < .001), for SDANN was 0.94 (P < .0001), and for ultra low frequency power was 0.96 (P < .0001). Deranged HRV in the early postburn period is a strong predictor of death. PMID:26061155

  9. Soil bacterial and fungal community dynamics in relation to Panax notoginseng death rate in a continuous cropping system.

    Science.gov (United States)

    Dong, Linlin; Xu, Jiang; Feng, Guangquan; Li, Xiwen; Chen, Shilin

    2016-01-01

    Notoginseng (Panax notoginseng), a valuable herbal medicine, has high death rates in continuous cropping systems. Variation in the soil microbial community is considered the primary cause of notoginseng mortality, although the taxa responsible for crop failure remains unidentified. This study used high-throughput sequencing methods to characterize changes in the microbial community and screen microbial taxa related to the death rate. Fungal diversity significantly decreased in soils cropped with notoginseng for three years. The death rate and the fungal diversity were significantly negatively correlated, suggesting that fungal diversity might be a potential bioindicator of soil health. Positive correlation coefficients revealed that Burkholderiales, Syntrophobacteraceae, Myrmecridium, Phaeosphaeria, Fusarium, and Phoma were better adapted to colonization of diseased plants. The relative abundance of Fusarium oxysporum (R = 0.841, P < 0.05) and Phaeosphaeria rousseliana (R = 0.830, P < 0.05) were positively associated with the death rate. F. oxysporum was a pathogen of notoginseng root-rot that caused seedling death. Negative correlation coefficients indicated that Thermogemmatisporaceae, Actinosynnemataceae, Hydnodontaceae, Herpotrichiellaceae, and Coniosporium might be antagonists of pathogens, and the relative abundance of Coniosporium perforans was negatively correlated with the death rate. Our findings provide a dynamic overview of the microbial community and present a clear scope for screening beneficial microbes and pathogens of notoginseng. PMID:27549984

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

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

    International Nuclear Information System (INIS)

    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. 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. 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. PIT induced massive cell death of targeted tumor cells immediately after exposure of NIR light that was demonstrated with BLI in vivo

  13. Survival rates among patients with cancer in Alberta in 1974-78.

    OpenAIRE

    Mao, Y.; Semenciw, R; Morrison, H.; Koch, M; Hill, G; Fair, M; Wigle, D

    1988-01-01

    We calculated 5-year crude and relative survival rates, by age and sex, for patients in Alberta in whom cancer was diagnosed between 1974 and 1978. Cancers with low overall 5-year relative survival rates (less than 35%) included stomach cancer, cancer of the pancreas, lung cancer, brain cancer, multiple myeloma and myeloid leukemia. Cancers with high overall 5-year relative survival rates (more than 70%) included melanoma, breast cancer, cancer of the uterus, cancer of the bladder and Hodgkin...

  14. Global epidemiology of hysterectomy: possible impact on gynecological cancer rates

    DEFF Research Database (Denmark)

    Hammer, Anne; Rositch, Anne; Kahlert, Johnny Abildgaard; Blaakær, Jan; Gravitt, Patti; Søgaard, Mette

    2015-01-01

    Despite the fact that hysterectomy is the most common surgical procedure worldwide in gynecology, national reporting of the incidence rate of gynecological cancers rarely removes the proportion no longer at risk of the disease from the population-at-risk-denominator (ie. women who have had a...... hysterectomy). The incidence rate of gynecological cancers is thus likely underestimated. Since hysterectomy, as well as oophorectomy, incidence varies across countries, age, and over time, meaningful comparison of gynecological cancer incidence rates may be compromised. Without accurate estimates of...... gynecological cancer incidence rates, performed via removing the proportion of hysterectomized or oophorectomized women from the population-at-risk-denominator, the impact of prevention strategies may be masked or misinterpreted. Furthermore, since national cervical cancer screening guidelines are at least in...

  15. Trends in Lung Cancer Incidence Rates, Oklahoma 2005–2010

    OpenAIRE

    Mowls, Dana S.; McCaffree, D. Robert; Beebe, Laura A.

    2015-01-01

    Purpose Lung cancer is the second most frequently diagnosed cancer among men and women in the United States. With cigarette smoking causing the majority of cases, patterns in lung cancer are often monitored to understand the impact of anti-tobacco efforts. The purpose of this research was to investigate trends in lung cancer incidence rates for the period 2005–2010 in Oklahoma. Methods Data on Oklahoma’s incident cases of lung cancer (2005–2010) were obtained from the Centers for Disease Cont...

  16. Prognostic factors affecting the all-cause death and sudden cardiac death rates of post myocardial infarction patients with low left ventricular ejection fraction

    Institute of Scientific and Technical Information of China (English)

    DAI Shi-mo; ZHANG Shu; CHEN Ke-ping; HUA Wei; WANG Fang-zheng; CHEN Xin

    2009-01-01

    Background Post myocardial infarction (post-MI) patients with low left ventricular ejection fraction (LVEF) have been candidates for an implantable cardioverter-deflbrillator (ICD) since the Multicenter Automatic Defibrillator Implantation Trail II (MADIT II).However,due to the high costs of ICDs,widespread usage has not been accepted.Therefore,further risk stratification for post-MI patients with low LVEF may aid in the selection of patients that will benefit most from ICD treatment.Methods Four hundred and seventeen post-MI patients with low LVEF (≤35%) were enrolled in the study.All the patients received standard examination and proper treatment and were followed up to observe the all-cause death rate and sudden cardiac death (SCD) rate.Then COX proportional-hazards regression model was used to investigate the clinical factors which affect the all-cause death rate and SCD rate.Results Of 55 patients who died during (32±24) months of follow-up,37 (67%) died suddenly.After adjusting for baseline clinical characteristics,multivariate COX proportional-hazards regression model identified the following variables associated with death from all causes:New York Heart Association (NYHA) heart failure class ≥111 (Hazard ratio:2.361),LVEF ≤20% (Hazard ratio:2.514),sustained ventricular tachycardia (Hazard ratio:6.453),and age ≥70 years (Hazard ratio:3.116).The presence of sustained ventricular tachycardia (Hazard ratio:6.491) and age ≥70 years (Hazard ratio:2.694) were specifically associated with SCD.Conclusions In the post-MI patients with low LVEF,factors as LVEF ≤20%,age ≥70 years,presence of ventricular tachycardia,and NYHA heart failure class≥111 predict an adverse outcome.The presence of sustained ventricular tachycardia and age ≥70 years was associated with occurrence of SCD in these patients.

  17. CDC Vital Signs: Breast Cancer

    Science.gov (United States)

    ... 2.65 MB] Read the MMWR Science Clips Breast Cancer Black Women Have Higher Death Rates from Breast ... of Page U.S. State Info Number of Additional Breast Cancer Deaths Among Black Women, By State SOURCE: National ...

  18. Estimating Benefits of Past, Current, and Future Reductions in Smoking Rates Using a Comprehensive Model With Competing Causes of Death

    OpenAIRE

    van Meijgaard, Jeroen; Fielding, Jonathan E.

    2012-01-01

    Introduction Despite years of declining smoking prevalence, tobacco use is still the leading preventable contributor to illness and death in the United States, and the effect of past tobacco-use control efforts has not fully translated into improvements in health outcomes. The objective of this study was to use a life course model with multiple competing causes of death to elucidate the ongoing benefits of tobacco-use control efforts on US death rates. Methods We used a continuous-time life c...

  19. Apoptosis Cell Death Effect of Scrophularia Variegata on Breast Cancer Cells via Mitochondrial Intrinsic Pathway

    Science.gov (United States)

    Azadmehr, Abbas; Hajiaghaee, Reza; Baradaran, Behzad; Haghdoost-Yazdi, Hashem

    2015-01-01

    Purpose: Scrophularia variegata M. Beib. (Scrophulariaceae) is an Iranian medicinal plant which is used for various inflammatory disorders in traditional medicine. In this study we evaluated the anti-cancer and cytotoxic effects of the Scrophularia variegata (S. variegata) ethanolic extract on the human breast cancer cell line. Methods: The cytotoxicity effect of the extract on MCF-7 cells was evaluated by MTT assay. In addition, Caspase activity, DNA ladder and Cell death were evaluated by ELISA, gel electrophoresis and Annexin V-FITC/PI staining, respectively. Results: The S. variegata extract showed significant effect cytotoxicity on MCF-7 human breast cancer cell line. Treatment with the extract induced apoptosis on the breast cancer cells by cell cycle arrest in G2/M phase. The results indicated that cytotoxicity activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation as well as an increase of the amount of caspase 3 and caspase 9. In addition, the phytochemical assay showed that the extract had antioxidant capacity and also flavonoids, phenolic compounds and phenyl propanoids were presented in the extract. Conclusion: Our findings indicated that S. variegata extract induced apoptosis via mitochondrial intrinsic pathway on breast cancer by cell cycle arrest in G2/M phase and an increase of caspase 3 and caspase 9. However future studies are needed. PMID:26504768

  20. Injecting drug users in Scotland, 2006: Listing, number, demography, and opiate-related death-rates.

    Science.gov (United States)

    King, Ruth; Bird, Sheila M; Overstall, Antony; Hay, Gordon; Hutchinson, Sharon J

    2013-06-01

    Using Bayesian capture-recapture analysis, we estimated the number of current injecting drug users (IDUs) in Scotland in 2006 from the cross-counts of 5670 IDUs listed on four data-sources: social enquiry reports (901 IDUs listed), hospital records (953), drug treatment agencies (3504), and recent Hepatitis C virus (HCV) diagnoses (827 listed as IDU-risk). Further, we accessed exact numbers of opiate-related drugs-related deaths (DRDs) in 2006 and 2007 to improve estimation of Scotland's DRD rates per 100 current IDUs. Using all four data-sources, and model-averaging of standard hierarchical log-linear models to allow for pairwise interactions between data-sources and/or demographic classifications, Scotland had an estimated 31700 IDUs in 2006 (95% credible interval: 24900-38700); but 25000 IDUs (95% CI: 20700-35000) by excluding recent HCV diagnoses whose IDU-risk can refer to past injecting. Only in the younger age-group (15-34 years) were Scotland's opiate-related DRD rates significantly lower for females than males. Older males' opiate-related DRD rate was 1.9 (1.24-2.40) per 100 current IDUs without or 1.3 (0.94-1.64) with inclusion of recent HCV diagnoses. If, indeed, Scotland had only 25000 current IDUs in 2006, with only 8200 of them aged 35+ years, the opiate-related DRD rate is higher among this older age group than has been appreciated hitherto. There is counter-balancing good news for the public health: the hitherto sharp increase in older current IDUs had stalled by 2006. PMID:23730265

  1. Metabolic Tumor Burden Predicts for Disease Progression and Death in Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: In lung cancer, stage is an important prognostic factor for disease progression and survival. However, stage may be simply a surrogate for underlying tumor burden. Our purpose was to assess the prognostic value of tumor burden measured by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging. Patients and Methods: We identified 19 patients with lung cancer who had staging PET-CT scans before any therapy, and adequate follow-up (complete to time of progression for 18, and death for 15 of 19). Metabolically active tumor regions were segmented on pretreatment PET scans semi-automatically using custom software. We determined the relationship between times to progression (TTP) and death (OS) and two PET parameters: total metabolic tumor volume (MTV), and standardized uptake value (SUV). Results: The estimated median TTP and OS for the cohort were 9.3 months and 14.8 months. On multivariate Cox proportional hazards regression analysis, an increase in MTV of 25 ml (difference between the 75th and 25th percentiles) was associated with increased hazard of progression and of death (5.4-fold and 7.6-fold), statistically significant (p = 0.0014 and p = 0.001) after controlling for stage, treatment intent (definitive or palliative), age, Karnofsky performance status, and weight loss. We did not find a significant relationship between SUV and TTP or OS. Conclusions: In this study, high tumor burden assessed by PET MTV is an independent poor prognostic feature in lung cancer, promising for stratifying patients in randomized trials and ultimately for selecting risk-adapted therapies. These results will need to be validated in larger cohorts with longer follow-up, and evaluated prospectively

  2. Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women's health initiative.

    Science.gov (United States)

    Gong, Zhihong; Aragaki, Aaron K; Chlebowski, Rowan T; Manson, JoAnn E; Rohan, Thomas E; Chen, Chu; Vitolins, Mara Z; Tinker, Lesley F; LeBlanc, Erin S; Kuller, Lewis H; Hou, Lifang; LaMonte, Michael J; Luo, Juhua; Wactawski-Wende, Jean

    2016-04-15

    Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women's Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p cancers (HR, 1.2-1.4, and up to over twofold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p cancer incidence by diabetes therapy (p = 0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 vs. 1.45; p = 0.007) and for breast cancer (HRs, 0.50 vs. 1.29; p = 0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer. PMID:26616262

  3. Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death

    International Nuclear Information System (INIS)

    To access the prognostic significance of HER-2 overexpression, the effect of trastuzumab and the cause of death in patients with brain metastases (BM) from breast cancer (BC). We analyzed the outcome of 130 patients with BM from BC who received whole-brain radiotherapy (WBRT) (without surgery or radiosurgery) between January 1998 and April 2006. Demographic data, tumor characteristics, and treatments were prospectively recorded. The impact of HER-2 overexpression and trastuzumab-based therapy on overall survival (OS) and the cause of death were evaluated. The median follow-up for the whole population was 6.25 months (mean: 9.15; range: 0.23-53). The median survival time and 1-year survival rates after BM diagnosis were 7.43 months and 35.8% (95% CI: 28-45.7) respectively. The median survival time for HER-2 negative patients (n = 78), HER-2 positive patients not treated with trastuzumab (n = 20) and HER-2 positive patients treated with trastuzumab (n = 32) were 5.9 months, 5.6 months and 19.53 months, respectively. The 1-year survival rates were 26.1%, 29.2% and 62.6% respectively, (p < 0.004). Among the 18 HER-2 positive patients treated with trastuzumab who died, 11 (61%) apparently succumbed from CNS progression, in the face of stable or responsive non-CNS disease. Trastuzumab-based therapy was associated with a 51% reduction in the risk of death (multiadjusted hazard ratio: 0.49; 95% CI, 0.29-0.83). In our experience, trastuzumab-based therapy for HER-overexpressing tumors was associated with improved survival in BM BC patients. This subgroup of patients may benefit from innovative approaches, in order to obtain better intra cerebral control

  4. Living in the face of death: Studies on palliative care in upper GI cancer patients

    OpenAIRE

    Uitdehaag, Madeleen

    2012-01-01

    textabstractThis thesis explores palliative care provided to patients with advanced upper gastrointestinal (GI) cancer. The 5-year survival rates for these cancer sites range between 4 and 17%, which implies that many of these patients require palliative care. Considering the fact that there is no uniform management policy aiming at improvement of quality of life (QoL) of these patients and their families, we decided to study different interventions with effect on this primary aim. The introd...

  5. LCL124, a Cationic Analog of Ceramide, Selectively Induces Pancreatic Cancer Cell Death by Accumulating in Mitochondria

    OpenAIRE

    Beckham, Thomas H; Lu, Ping; Jones, Elizabeth E.; Marrison, Tucker; Lewis, Clayton S.; Cheng, Joseph C.; Ramshesh, Venkat K.; Beeson, Gyda; Beeson, Craig C.; Richard R. Drake; Bielawska, Alicja; Bielawski, Jacek; Szulc, Zdzislaw M; Ogretmen, Besim; Norris, James S.

    2013-01-01

    Treatment of pancreatic cancer that cannot be surgically resected currently relies on minimally beneficial cytotoxic chemotherapy with gemcitabine. As the fourth leading cause of cancer-related death in the United States with dismal survival statistics, pancreatic cancer demands new and more effective treatment approaches. Resistance to gemcitabine is nearly universal and appears to involve defects in the intrinsic/mitochondrial apoptotic pathway. The bioactive sphingolipid ceramide is a crit...

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

    OpenAIRE

    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

    2011-01-01

    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 ...

  7. NCHS - Age-adjusted death rates and life-expectancy at birth, (All Races, Both Sexes): United States, 1900-2013

    Data.gov (United States)

    U.S. Department of Health & Human Services — Age-adjusted death rates (deaths per 100,000) are based on the 2000 U.S. standard population. Populations used for computing death rates for 2011–2013 are...

  8. Bone Cancer Rates in Dinosaurs Compared with Modern Vertebrates

    CERN Document Server

    Natarajan, L C; Rothschild, B M; Martin, L D

    2007-01-01

    Data on the prevalence of bone cancer in dinosaurs is available from past radiological examination of preserved bones. We statistically test this data for consistency with rates extrapolated from information on bone cancer in modern vertebrates, and find that there is no evidence of a different rate. Thus, this test provides no support for a possible role of ionizing radiation in the K-T extinction event.

  9. Low dose rate Ir-192 interstitial brachytherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oki, Yosuke; Dokiya, Takushi; Yorozu, Atsunori; Suzuki, Takayuki; Saito, Shiro; Monma, Tetsuo; Ohki, Takahiro [National Tokyo Medical Center (Japan); Murai, Masaru; Kubo, Atsushi

    2000-04-01

    From December 1997 through January 1999, fifteen prostatic cancer patients were treated with low dose rate Ir-192 interstitial brachytherapy using TRUS and perineal template guidance without external radiotherapy. Up to now, as no apparent side effects were found, the safety of this treatment is suggested. In the future, in order to treat prostatic cancer patients with interstitial brachytherapy using I-125 or Pd-103, more investigation for this low dose rate Ir-192 interstitial brachytherapy is needed. (author)

  10. Non-chemotoxic induction of cancer cell death using magnetic nanowires

    KAUST Repository

    Contreras, Maria

    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.

  11. High dose rate interstitial radiation for tongue cancer

    International Nuclear Information System (INIS)

    From April 1992 through March 1995, 38 patients with T1-2N0 tongue cancer were treated with high dose rate (HDR) or low dose rate (LDR) brachytherapy alone. Three year local control rates of HDR and LDR groups were 94% and 90%, respectively. Treatment results and complication of HDR brachytherapy were almost the same as those of LDR brachytherapy. At the same period, 11 patients with T1-2N0-2 tongue cancer were treated with external radiation and HDR brachytherapy. Three year local control rate was 90%. HDR brachytherapy have some advantages compared with LDR brachytherapy. (author)

  12. 1985 Cancer Facts and Figures.

    Science.gov (United States)

    American Cancer Society, Inc., New York, NY.

    Information and statistical data about cancer are provided in seven categories. They include: (1) basic cancer data (considering how cancer works, trends in diagnosis and treatment, new cancer cases and deaths for 1985, and other areas); (2) major cancer sites (discussing lung cancer, colorectal cancer, breast cancer, 5-year survival rates/trends…

  13. Congruencies in Increased Mortality Rates, Years of Potential Life Lost, and Causes of Death Among Public Mental Health Clients in Eight States

    Directory of Open Access Journals (Sweden)

    Craig W. Colton, PhD

    2006-03-01

    Full Text Available Introduction Mortality rates are used as global measures of a population’s health status and as indicators for public health efforts and medical treatments. Elevated mortality rates among individuals with mental illness have been reported in various studies, but very little focus has been placed on interstate comparisons and congruency of mortality and causes of death among public mental health clients. Methods Using age-adjusted death rates, standardized mortality ratios, and years of potential life lost, we compared the mortality of public mental health clients in eight states with the mortality of their state general populations. The data used in our study were submitted by public mental health agencies in eight states (Arizona, Missouri, Oklahoma, Rhode Island, Texas, Utah, Vermont, and Virginia for 1997 through 2000 during the Sixteen-State Study on Mental Health Performance Measures, a multistate study federally funded by the Center for Mental Health Services in collaboration with the National Association of State Mental Health Program Directors. Results In all eight states, we found that public mental health clients had a higher relative risk of death than the general populations of their states. Deceased public mental health clients had died at much younger ages and lost decades of potential life when compared with their living cohorts nationwide. Clients with major mental illness diagnoses died at younger ages and lost more years of life than people with non-major mental illness diagnoses. Most mental health clients died of natural causes similar to the leading causes of death found nationwide, including heart disease, cancer, and cerebrovascular, respiratory, and lung diseases. Conclusion Mental health and physical health are intertwined; both types of care should be provided and linked together within health care delivery systems. Research to track mortality and primary care should be increased to provide information for additional

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

    International Nuclear Information System (INIS)

    Proton beam has been applied to treat various tumor patients in clinical studies. However, it is still undefined whether proton radiation can inhibit the blood vessel formation and induce the cell death in vascular endothelial cells in growing organs. The aim of this study are first, to develop an optimal animal model for the observation of blood vessel development with low dose of proton beam and second, to investigate the effect of low dose proton beam on the inhibition of blood vessel formation induced by hypoxic conditions. In this study, flk1-GFP transgenic zebrafish embryos were used to directly visualize and determine the inhibition of blood vessels by low dose (1, 2, 5 Gy) of proton beam with spread out Bragg peak (SOBP). And we observed cell death by acridine orange staining at 96 hours post fertilization (hpf) stage of embryos after proton irradiation. We also compared the effects of proton beam with those of gamma-ray. An antioxidant, N-acetyl cystein (NAC) was used to investigate whether reactive oxygen species (ROS) were involved in the cell deaths induced by proton irradiation. Irradiated flk-1-GFP transgenic embryos with proton beam irradiation (35 MeV, spread out Bragg peak, SOBP) demonstrated a marked inhibition of embryonic growth and an altered fluorescent blood vessel development in the trunk region. When the cells with DNA damage in the irradiated zebrafish were stained with acridine orange, green fluorescent cell death spots were increased in trunk regions compared to non-irradiated control embryos. Proton beam also significantly increased the cell death rate in human umbilical vein endothelial cells (HUVEC), but pretreatment of N-acetyl cystein (NAC), an antioxidant, recovered the proton-induced cell death rate (p<0.01). Moreover, pretreatment of NAC abrogated the effect of proton beam on the inhibition of trunk vessel development and malformation of trunk truncation. From this study, we found that proton radiation therapy can inhibit the

  15. Comparison of total and cardiovascular death rates in the same city during a losing versus winning super bowl championship.

    Science.gov (United States)

    Kloner, Robert A; McDonald, Scott; Leeka, Justin; Poole, W Kenneth

    2009-06-15

    The purpose of this study was to determine whether there were changes in death rates when a local football team participated in the Super Bowl. Los Angeles (LA) played in the Super Bowl twice: on January 20, 1980 (LA Rams vs Pittsburgh Steelers, which LA lost), and on January 22, 1984 (LA Raiders vs Washington Redskins, which LA won). Data from LA County were analyzed for all-cause and circulatory death rates for the Super Bowl and the following 14 days when LA played (Super Bowl-related days) and control days (from January 15 to the end of February for 1980 to 1983 and 1984 to 1988). The Super Bowl-related days during LA's losing 1980 game were associated with higher daily death rates in LA County (per 100,000 population) for all deaths (2.4482 vs 2.0968 for control days, p intensity of a game played by a sports team in a highly publicized rivalry such as the Super Bowl can trigger total and cardiovascular deaths. PMID:19539070

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

    Directory of Open Access Journals (Sweden)

    Petter Storm

    Full Text Available 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.

  17. Regulatory mechanism of radiation-induced cancer cell death by the change of cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Soo Jin; Jeong, Min Ho; Jang, Ji Yeon [College of Medicine, Donga Univ., Pusan (Korea, Republic of)

    2003-09-01

    cycle regulatory activites. In this study, we present a unique and reproducible model in which for investigating the mechanisms of various, radiation-induced, cancer cell death patterns. Further evaluation by using this model will provide a potent target for a new strategy of radiotherapy.

  18. VMP1 related autophagy and apoptosis in colorectal cancer cells: VMP1 regulates cell death

    Energy Technology Data Exchange (ETDEWEB)

    Qian, Qinyi [Department of Ultrasonograph, Changshu No. 2 People’s Hospital, Changshu (China); Zhou, Hao; Chen, Yan [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China); Shen, Chenglong [Department of General Surgery, Changshu No. 2 People’s Hospital, Changshu (China); He, Songbing; Zhao, Hua; Wang, Liang [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China); Wan, Daiwei, E-mail: 372710369@qq.com [Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou (China); Gu, Wen, E-mail: 505339704@qq.com [Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou (China)

    2014-01-17

    Highlights: •This research confirmed VMP1 as a regulator of autophagy in colorectal cancer cell lines. •We proved the pro-survival role of VMP1-mediated autophagy in colorectal cancer cell lines. •We found the interaction between VMP1 and BECLIN1 also existing in colorectal cancer cell lines. -- Abstract: Vacuole membrane protein 1 (VMP1) is an autophagy-related protein and identified as a key regulator of autophagy in recent years. In pancreatic cell lines, VMP1-dependent autophagy has been linked to positive regulation of apoptosis. However, there are no published reports on the role of VMP1 in autophagy and apoptosis in colorectal cancers. Therefore, to address this gap of knowledge, we decided to interrogate regulation of autophagy and apoptosis by VMP1. We have studied the induction of autophagy by starvation and rapamycin treatment in colorectal cell lines using electron microscopy, immunofluorescence, and immunoblotting. We found that starvation-induced autophagy correlated with an increase in VMP1 expression, that VMP1 interacted with BECLIN1, and that siRNA mediated down-regulation of VMP1-reduced autophagy. Next, we examined the relationship between VMP1-dependent autophagy and apoptosis and found that VMP1 down-regulation sensitizes cells to apoptosis and that agents that induce apoptosis down-regulate VMP1. In conclusion, similar to its reported role in other cell types, VMP1 is an important regulator of autophagy in colorectal cell lines. However, in contrast to its role in pancreatic cell lines, in colorectal cancer cells, VMP1-dependent autophagy appears to be pro-survival rather than pro-cell death.

  19. VMP1 related autophagy and apoptosis in colorectal cancer cells: VMP1 regulates cell death

    International Nuclear Information System (INIS)

    Highlights: •This research confirmed VMP1 as a regulator of autophagy in colorectal cancer cell lines. •We proved the pro-survival role of VMP1-mediated autophagy in colorectal cancer cell lines. •We found the interaction between VMP1 and BECLIN1 also existing in colorectal cancer cell lines. -- Abstract: Vacuole membrane protein 1 (VMP1) is an autophagy-related protein and identified as a key regulator of autophagy in recent years. In pancreatic cell lines, VMP1-dependent autophagy has been linked to positive regulation of apoptosis. However, there are no published reports on the role of VMP1 in autophagy and apoptosis in colorectal cancers. Therefore, to address this gap of knowledge, we decided to interrogate regulation of autophagy and apoptosis by VMP1. We have studied the induction of autophagy by starvation and rapamycin treatment in colorectal cell lines using electron microscopy, immunofluorescence, and immunoblotting. We found that starvation-induced autophagy correlated with an increase in VMP1 expression, that VMP1 interacted with BECLIN1, and that siRNA mediated down-regulation of VMP1-reduced autophagy. Next, we examined the relationship between VMP1-dependent autophagy and apoptosis and found that VMP1 down-regulation sensitizes cells to apoptosis and that agents that induce apoptosis down-regulate VMP1. In conclusion, similar to its reported role in other cell types, VMP1 is an important regulator of autophagy in colorectal cell lines. However, in contrast to its role in pancreatic cell lines, in colorectal cancer cells, VMP1-dependent autophagy appears to be pro-survival rather than pro-cell death

  20. Non-canonical kinase signaling by the death ligand TRAIL in cancer cells : discord in the death receptor family

    NARCIS (Netherlands)

    Azijli, K.; Weyhenmeyer, B.; Peters, G. J.; de Jong, S.; Kruyt, F. A. E.

    2013-01-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-based therapy is currently evaluated in clinical studies as a tumor cell selective pro-apoptotic approach. However, besides activating canonical caspase-dependent apoptosis by binding to TRAIL-specific death receptors, the TRAIL ligand

  1. Cytotoxic hydrogen bridged ruthenium quinaldamide complexes showing induced cancer cell death by apoptosis.

    Science.gov (United States)

    Lord, Rianne M; Allison, Simon J; Rafferty, Karen; Ghandhi, Laura; Pask, Christopher M; McGowan, Patrick C

    2016-08-16

    This report presents the first known p-cymene ruthenium quinaldamide complexes which are stabilised by a hydrogen-bridging atom, [{(p-cym)Ru(II)X(N,N)}{H(+)}{(N,N)XRu(II)(p-cym)}][PF6] (N,N = functionalised quinaldamide and X = Cl or Br). These complexes are formed by a reaction of [p-cymRu(μ-X)2]2 with a functionalised quinaldamide ligand. When filtered over NH4PF6, and under aerobic conditions the equilibrium of NH4PF6 ⇔ NH3 + HPF6 enables incorporation of HPF6 and the stabilisation of two monomeric ruthenium complexes by a bridging H(+), which are counter-balanced by a PF6 counterion. X-ray crystallographic analysis is presented for six new structures with OO distances of 2.420(4)-2.448(15) Å, which is significant for strong hydrogen bonds. Chemosensitivity studies against HCT116, A2780 and cisplatin-resistant A2780cis human cancer cells showed the ruthenium complexes with a bromide ancillary ligand to be more potent than those with a chloride ligand. The 4'-fluoro compounds show a reduction in potency for both chloride and bromide complexes against all cell lines, but an increase in selectivity towards cancer cells compared to non-cancer ARPE-19 cells, with a selectivity index >1. Mechanistic studies showed a clear correlation between IC50 values and induction of cell death by apoptosis. PMID:27417660

  2. IKK inhibitor suppresses epithelial-mesenchymal transition and induces cell death in prostate cancer.

    Science.gov (United States)

    Ping, Hao; Yang, Feiya; Wang, Mingshuai; Niu, Yinong; Xing, Nianzeng

    2016-09-01

    IκB kinase (IKK)/nuclear factor κB (NF-κB) pathway activation is a key event in the acquisition of invasive and metastatic capacities in prostate cancer. A potent small-molecule compound, BMS-345541, was identified as a highly selective IKKα and IKKβ inhibitor to inhibit kinase activity. This study explored the effect of IKK inhibitor on epithelial-mesenchymal transition (EMT), apoptosis and metastasis in prostate cancer. Here, we demonstrate the role of IKK inhibitor reducing proliferation and inducing apoptosis in PC-3 cells. Furthermore, BMS345541 inhibited IκBα phosphorylation and nuclear level of NF-κB/p65 in PC-3 cells. We also observed downregulation of the N-cadherin, Snail, Slug and Twist protein in a dose-dependent manner. BMS‑345541 induced upregulation of the epithelial marker E-cadherin and phosphorylated NDRG1 at protein level. Moreover, BMS‑345541 reduced invasion and metastasis of PC-3 cells in vitro. In conclusion, IKK has a key role in both EMT and apoptosis of prostate cancer. IKK inhibitor can reverse EMT and induce cell death in PCa cells. IKK was identified as a potential target structure for future therapeutic intervention in PCa. PMID:27432067

  3. Correlation of Alzheimer's disease death rates with historical per capita personal income in the USA.

    Directory of Open Access Journals (Sweden)

    Dariusz Stępkowski

    Full Text Available Alzheimer's disease (AD is a progressive degenerating disease of complex etiology. A variety of risk factors contribute to the chance of developing AD. Lifestyle factors, such as physical, mental and social activity, education, and diet all affect the susceptibility to developing AD. These factors are in turn related to the level of personal income. Lower income usually coincides with lower level of education, lesser mental, leisure-social and physical activity, and poorer diet. In the present paper, we have analyzed the correlation of historical (1929-2011 per capita personal income (PCPI for all states of the USA with corresponding age-adjusted AD death rates (AADR for years 2000, 2005 and 2008. We found negative correlations in all cases, the highest one (R ≈ -0.65 for the PCPIs in the year 1970 correlated against the AADRs in 2005. From 1929 to 2005 the R value varies in an oscillatory manner, with the strongest correlations in 1929, 1970, 1990 and the weakest in 1950, 1980, 1998. Further analysis indicated that this oscillatory behavior of R is not artificially related to the economic factors but rather to delayed biological consequences associated with personal income. We conclude that the influence of the income level on the AD mortality in 2005 was the highest in the early years of life of the AD victims. Overall, the income had a significant, lifelong, albeit constantly decreasing, influence on the risk of developing AD. We postulate that the susceptibility of a population to late-onset AD (LOAD is determined to a large extent by the history of income-related modifiable lifestyle risk factors. Among these risk factors, inappropriate diet has a significant contribution.

  4. Reduced death rates from cyclones in Bangladesh: What more needs to be done?

    OpenAIRE

    Haque, Ubydul; Hashizume, Masahiro; Kolivras, Korine; Overgaard, Hans J.; Das, Bivash; Yamamoto, Taro

    2012-01-01

    Tropical storms, such as cyclones, hurricanes and typhoons, present major threats to coastal communities. Around two million people worldwide have died and millions have been injured over the past two centuries as a result of tropical storms. Bangladesh is especially vulnerable to tropical cyclones, with around 718 000 deaths from them in the past 50 years. However, cyclone-related mortality in Bangladesh has declined by more than 100-fold over the past 40 years, from 500 000 deaths in 1970 t...

  5. Disparities in late stage diagnosis, treatment, and breast cancer-related death by race, age, and rural residence among women in Georgia.

    Science.gov (United States)

    Markossian, Talar W; Hines, Robert B

    2012-01-01

    The objectives of this study were to examine the outcomes of late stage breast cancer diagnosis, receiving first course treatment, and breast cancer-related death by race, age, and rural/urban residence in Georgia. The authors used cross-sectional and follow-up data (1992-2007) for Atlanta and Rural Georgia cancer registries that are part of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (N = 23,500 incident breast cancer cases in non-Hispanic whites or non-Hispanic African Americans). Multilevel modeling and Cox proportional hazard models revealed that compared to whites, African American women had significantly increased odds of late stage diagnosis (odds ratio [OR] = 2.08, p = 0.0001) and unknown tumor stage (OR = 1.27, p = 0.0001), decreased odds of receiving radiation (OR = 0.93, p = 0.041) or surgery (OR = 0.50, p = 0.0001), and increased risk of death following breast cancer diagnosis (hazard rate ratio [HR] = 1.50, p = 0.0001). Increased age was significantly associated with the odds of late/unknown stage at diagnosis, worse treatment, and survival. Women residing in rural areas had significantly decreased odds of receiving radiation and surgery with radiation (OR = 0.59, p = 0.0001), and for receiving breast-conserving surgery compared to mastectomy (OR = 0.73, p = 0.005). Factors affecting each level of the breast cancer continuum are distinct and should be examined separately. Efforts are needed to alleviate disparities in breast cancer outcomes in hard-to-reach populations. PMID:22591230

  6. Programmed cell death ligand 1 (PD-L1) expression on gastric cancer and its relationship with clinicopathologic factors

    OpenAIRE

    Zhang, Lin; Qiu, Miaozhen; Jin, Ying; Ji, Jiao; Li, Baoxia; Wang, Xueping; Yan, Shumei; Xu, Ruihua; Yang, Dajun

    2015-01-01

    Background: Targeting the immune checkpoints in solid tumors becomes hot recently. Programmed cell death ligand 1 (PD-L1) is ligand for programmed death 1 (PD-1), which is known to negatively regulate T-cell activation. In the present study, we investigated the expression of PD-L1 in tumor specimens of gastric cancer and its relationships with clinicopathological variables and survival. Methods: The expression of PD-L1 in 132 surgically resected specimens of stage II and III gastric cancer wa...

  7. Fear of death, mortality communication, and psychological distress among secular and religiously observant family caregivers of terminal cancer patients.

    Science.gov (United States)

    Bachner, Yaacov G; O'Rourke, Norm; Carmel, Sara

    2011-02-01

    Previous research suggests that caregivers and terminally ill patients face substantial difficulties discussing illness and death. Existing research, however, has focused primarily on the experience of patients. The current study compared responses as well as the relative strength of association between mortality comunication, fear of death, and psychological distress (i.e., depressive symptomatology, emotional exhaustion) among secular and religiously observant family caregivers of terminally ill cancer patients. A total of 236 participants were recruited over 18 months within the first year of caregiver bereavement. Retrospectively reported mortality communication was statistically greater among secular caregivers; in contrast, both fear of death and depressive symptoms were greater among the religiously observant. Path analyses subsequently revealed notable differences between groups. Among secular caregivers, a significant inverse relationship between mortality communication and the two indices of caregiver distress emerged. In contrast, the association between mortality communication and psychological distress among the religious was moderated by these caregivers' fear of death. The results of this study suggest that fear of death is a significant predictor of psychological distress among religiously observant caregivers of terminal cancer patients (i.e., fear of their own death as elicited by the caregiving role). Fostering morality communication between secular caregivers and patients would appear to be one means of reducing the likelihood of clinically significant psychological distress. This may be insufficient among religiously observant caregivers, however, for whom fear of death may first need to be redressed. PMID:24501834

  8. Birth and death rate estimates of cats and dogs in U.S. households and related factors.

    Science.gov (United States)

    New, John C; Kelch, William J; Hutchison, Jennifer M; Salman, Mo D; King, Mike; Scarlett, Janet M; Kass, Philip H

    2004-01-01

    Studies report variable factors associated with dog and cat surpluses in the United States. Estimates of cat and dog birth and death rates help understand the problem. This study collected data through a commercial survey company, distributing questionnaires to 7,399 cat- and dog-owning households (HHs) in 1996. The study used an unequal probability sampling plan and reported estimates of means and variances as weighted averages. The study used estimates of HHs and companion animals for national projections. More than 9 million owned cats and dogs died during 1996-yielding crude death rates of 8.3 cat deaths/100 cats in HHs and 7.9 dog deaths/100 dogs in HHs. The study reported twice as many kitten as puppy litters, with an average litter size of 5.73 and 7.57, respectively. The study reported data on planned versus unplanned litters, reasons caregivers did not spay females, disposition of litters, and sources of animals added to HHs. These first national estimates indicate the magnitude of, and reasons for, animals leaving HHs. The crude birth rate was estimated to be 11.2 kittens/100 cats in HHs and 11.4 puppies/100 dogs in HHs. PMID:15857809

  9. A simple algebraic cancer equation: calculating how cancers may arise with normal mutation rates

    Directory of Open Access Journals (Sweden)

    Shibata Darryl

    2010-01-01

    Full Text Available Abstract Background The purpose of this article is to present a relatively easy to understand cancer model where transformation occurs when the first cell, among many at risk within a colon, accumulates a set of driver mutations. The analysis of this model yields a simple algebraic equation, which takes as inputs the number of stem cells, mutation and division rates, and the number of driver mutations, and makes predictions about cancer epidemiology. Methods The equation [p = 1 - (1 - (1 - (1 - udkNm ] calculates the probability of cancer (p and contains five parameters: the number of divisions (d, the number of stem cells (N × m, the number of critical rate-limiting pathway driver mutations (k, and the mutation rate (u. In this model progression to cancer "starts" at conception and mutations accumulate with cell division. Transformation occurs when a critical number of rate-limiting pathway mutations first accumulates within a single stem cell. Results When applied to several colorectal cancer data sets, parameter values consistent with crypt stem cell biology and normal mutation rates were able to match the increase in cancer with aging, and the mutation frequencies found in cancer genomes. The equation can help explain how cancer risks may vary with age, height, germline mutations, and aspirin use. APC mutations may shorten pathways to cancer by effectively increasing the numbers of stem cells at risk. Conclusions The equation illustrates that age-related increases in cancer frequencies may result from relatively normal division and mutation rates. Although this equation does not encompass all of the known complexity of cancer, it may be useful, especially in a teaching setting, to help illustrate relationships between small and large cancer features.

  10. Novel self-micellizing anticancer lipid nanoparticles induce cell death of colorectal cancer cells.

    Science.gov (United States)

    Sundaramoorthy, Pasupathi; Baskaran, Rengarajan; Mishra, Siddhartha Kumar; Jeong, Keun-Yeong; Oh, Seung Hyun; Kyu Yoo, Bong; Kim, Hwan Mook

    2015-11-01

    In the present study, we developed a novel drug-like self-micellizing anticancer lipid (SMAL), and investigated its anticancer activity and effects on cell death pathways in human colorectal cancer (CRC) cell lines. Three self-assembled nanoparticles were prepared, namely, SMAL102 (lauramide derivative), SMAL104 (palmitamide derivative), and SMAL108 (stearamide derivative) by a thin-film hydration technique, and were characterized for physicochemical and biological parameters. SMAL102 were nanosized (160.23 ± 8.11 nm) with uniform spherical shape, while SMAL104 and SMAL108 did not form spherical shape but formed large size nanoparticles and irregular in shape. Importantly, SMAL102 showed a cytotoxic effect towards CRC cell lines (HCT116 and HT-29), and less toxicity to a normal colon fibroblast cell line (CCD-18Co). Conversely, SMAL104 and SMAL108 did not have an anti-proliferative effect on CRC cell lines. SMAL102 nanoparticles were actively taken up by CRC cell lines, localized in the cell membrane, and exhibited remarkable cytotoxicity in a concentration-dependent manner. The normal colon cell line showed significantly less cellular uptake and non-cytotoxicity as compared with the CRC cell lines. SMAL102 nanoparticles induced caspase-3, caspase-9, and PARP cleavage in HT-29 cells, indicating the induction of apoptosis; whereas LC3B was activated in HCT116 cells, indicating autophagy-induced cell death. Collectively, these results demonstrate that SMAL102 induced cell death via activation of apoptosis and autophagy in CRC cell lines. The present study could be a pioneer for further preclinical and clinical development of such compounds. PMID:26342325

  11. Dr. Josef Steiner Cancer Research Prize Lecture: the role of physiological cell death in neoplastic transformation and in anti-cancer therapy.

    Science.gov (United States)

    Strasser, A

    1999-05-17

    Cell death is a physiological process which is required for normal development and existence of multi-cellular organisms. Physiological cell death, or apoptosis, is controlled by an evolutionarily conserved mechanism. Abnormalities in this process are implicated as a cause or contributing factor in a variety of diseases. Inhibition of apoptosis can promote neoplastic transformation, particularly in combination with dysregulated cell-cycle control, and can influence the response of tumour cells to anti-cancer therapy. Molecular biological and biochemical approaches are used to find missing cell-death regulators and to define signalling cascades, while experiments in genetically modified mice will identify the essential function of these molecules. Discoveries from cell death research should provide clues for designing therapies for a variety of diseases, including degenerative disorders, auto-immunity and cancer. PMID:10225436

  12. Regional variations in mortality rates of pancreatic cancer in China:Results from 1990-1992 national mortality survey

    Institute of Scientific and Technical Information of China (English)

    Ke-Xin Chen; Peizhong Peter Wang; Si-Wei Zhang; Lian-Di Li; Feng-Zhu Lu; Xi-Shan Hao

    2003-01-01

    AIM: To examine the regional variations in mortality rates of pancreatic cancer in China.METHODS: Aggregated mortality data of pancreatic cancer were extracted from the 1990-1992 national death of all causes and its mortality survey in China. Age specific and standardized mortality rates were calculated at both national and provincial levels with selected characteristics including sex and residence status.RESULTS: Mortality of pancreatic cancer ranked the ninth and accounted for 1.38 percent of the total malignancy deaths. The crude and age standardized mortality rates of pancreatic cancer in China in the period of 1990-1992 were 1.48/100 000 and 1.30/100 000, respectively. Substantial regional variations in mortality rates across China were observed with adjusted mortality rates ranging from 0.43/100 000 to 3.70/100 000 with an extremal value of 8.7.Urban residents had significant higher pancreatic mortality than rural residents.CONCLUSION: The findings of this study show different mortality rates of this disease and highlight the importance of further investigation on factors, which might contribute to the observed epidemiological patterns.

  13. Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers

    OpenAIRE

    Carbognin, Luisa; Pilotto, Sara; Milella, Michele; Vaccaro, Vanja; Brunelli, Matteo; Caliò, Anna; Cuppone, Federica; Sperduti, Isabella; Giannarelli, Diana; Chilosi, Marco; Bronte, Vincenzo; Scarpa, Aldo; Bria, Emilio; Tortora, Giampaolo

    2015-01-01

    Background The potential predictive role of programmed death-ligand-1 (PD-L1) expression on tumor cells in the context of solid tumor treated with checkpoint inhibitors targeting the PD-1 pathway represents an issue for clinical research. Methods Overall response rate (ORR) was extracted from phase I-III trials investigating nivolumab, pembrolizumab and MPDL3280A for advanced melanoma, non-small cell lung cancer (NSCLC) and genitourinary cancer, and cumulated by adopting a fixed and random-ef...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. YM155 potently triggers cell death in breast cancer cells through an autophagy-NF-kB network.

    Science.gov (United States)

    Véquaud, Eloïse; Séveno, Céline; Loussouarn, Delphine; Engelhart, Lucie; Campone, Mario; Juin, Philippe; Barillé-Nion, Sophie

    2015-05-30

    Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first "Survivin suppressant" but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. We herein show that YM155 exerts single agent toxicity on primary breast cancer cells grown in an ex vivo assay preserving tumor microenvironment. In vitro assays indicate that YM155 more efficiently triggers cell death in breast cancer cells (including these with stem-cell like properties) than in non tumorigenic mammary cells. YM155-induced cell death is critically dependent on autophagy and NF-kB but independent of p53 and it coïncides with DNA damage and a DNA damage response in p53-proficient cells. Our results point out a crosstalk between NF-kB and autophagy controlling YM155-induced death in breast cancer cells and argue for the potential use of YM155 as a genotoxic agent in breast cancer therapy. PMID:25974963

  16. Reduced death rates from cyclones in Bangladesh: what more needs to be done?

    OpenAIRE

    Haque, Ubydul; Hashizume, Masahiro; Kolivras, Korine N.; Overgaard, Hans J.; Das, Bivash; Yamamoto, Taro

    2011-01-01

    Tropical storms, such as cyclones, hurricanes and typhoons, present major threats to coastal communities. Around two million people worldwide have died and millions have been injured over the past two centuries as a result of tropical storms. Bangladesh is especially vulnerable to tropical cyclones, with around 718 000 deaths from them in the past 50 years. However, cyclone-related mortality in Bangladesh has declined by more than 100-fold over the past 40 years, from 500 000 deaths in 1970 t...

  17. Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

    International Nuclear Information System (INIS)

    Purpose: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. Methods and Materials: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose ≥75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. Results: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8–10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. Conclusions: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8 10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

  18. Perineural Invasion Predicts Increased Recurrence, Metastasis, and Death From Prostate Cancer Following Treatment With Dose-Escalated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Felix Y. [University of Michigan Medical Center, Ann Arbor, MI (United States); Ann Arbor Veteran Affairs Medical System, Ann Arbor, MI (United States); Qian Yushen; Stenmark, Matthew H.; Halverson, Schuyler; Blas, Kevin; Vance, Sean [University of Michigan Medical Center, Ann Arbor, MI (United States); Sandler, Howard M. [Cedars Sinai Medical System, Los Angeles, CA (United States); Hamstra, Daniel A., E-mail: dhamm@med.umich.edu [University of Michigan Medical Center, Ann Arbor, MI (United States)

    2011-11-15

    Purpose: To assess the prognostic value of perineural invasion (PNI) for patients treated with dose-escalated external-beam radiation therapy for prostate cancer. Methods and Materials: Outcomes were analyzed for 651 men treated for prostate cancer with EBRT to a minimum dose {>=}75 Gy. We assessed the impact of PNI as well as pretreatment and treatment-related factors on freedom from biochemical failure (FFBF), freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival. Results: PNI was present in 34% of specimens at biopsy and was significantly associated with higher Gleason score (GS), T stage, and prostate-specific antigen level. On univariate and multivariate analysis, the presence of PNI was associated with worse FFBF (hazard ratio = 1.7, p <0.006), FFM (hazard ratio = 1.8, p <0.03), and CSS (HR = 1.4, p <0.05) compared with absence of PNI; there was no difference in overall survival. Seven-year rates of FFBF, FFM, and CCS were 64% vs. 80%, 84% vs. 92%, and 91% vs. 95% for those patients with and without PNI, respectively. On recursive partitioning analysis, PNI predicted for worse FFM and CSS in patients with GS 8-10, with FFM of 67% vs. 89% (p <0.02), and CSS of 69% vs. 91%, (p <0.04) at 7 years for those with and without PNI, respectively. Conclusions: The presence of PNI in the prostate biopsy predicts worse clinical outcome for patients treated with dose-escalated external-beam radiation therapy. Particularly in patients with GS 8-10 disease, the presence of PNI suggests an increased risk of metastasis and prostate cancer death.

  19. Mortality Rates and Causes of Death of Convicted Dutch Criminals 25 Years Later

    NARCIS (Netherlands)

    Nieuwbeerta, Paul; Piquero, Alex R.

    2008-01-01

    Extant theory hypothesizes that offenders have greater risk of premature and unnatural death than nonoffenders, but few studies have assessed this hypothesis; those doing so have relied on U.S. samples of male offenders typically followed until midlife. This article examines the relation between cri

  20. 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

    . Live 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...

  1. Bereavement Experiences of Mothers and Fathers over Time after the Death of a Child due to Cancer

    Science.gov (United States)

    Alam, Rifat; Barrera, Maru; D'Agostino, Norma; Nicholas, David B.; Schneiderman, Gerald

    2012-01-01

    The authors investigated longitudinally bereavement in mothers and fathers whose children died of cancer. Thirty-one parents were interviewed 6 and 18 months post-death. Analyses revealed parental differences and changes over time: (a) employment--fathers were more work-focused; (b) grief reactions--mothers expressed more intense grief reactions…

  2. Sensitization of (colon) cancer cells to death receptor related therapies A report from the FP6-ONCODEATH research consortium

    Czech Academy of Sciences Publication Activity Database

    Pintzas, A.; Zhivotovsky, B.; Workman, P.; Clarke, P.A.; Linardopoulos, S.; Martinou, J.C.; Lacal, J.C.; Robine, S.; Nasioulas, G.; Anděra, Ladislav

    2012-01-01

    Roč. 13, č. 7 (2012), s. 458-466. ISSN 1538-4047 Grant ostatní: EK(XE) LSHC-CT-2006-037278 Institutional support: RVO:68378050 Keywords : cancer * death receptors * kinase inhibitors * mitochondria * targeted therapies Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.287, year: 2012

  3. Review of Cancer Immunotherapy: Application of Chimeric Antigen Receptor T Cells and Programmed Death 1/Programmed Death-ligand 1 Antibodies

    Directory of Open Access Journals (Sweden)

    Tengfei Zhang

    2015-01-01

    Full Text Available Cancer immunotherapy strategies based on chimeric antigen receptor (CAR transduced T cells or antibodies against immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4 and programmed death 1 (PD-1, achieved significant successes from bench to clinic in the past 2 years. CARs are artificial engineered receptors that can specifically target tumor cell surface antigen, activate T cell and further enhance T cell function, independent of major histocompatibility complex. CAR T cells have shown promising outcomes in cancers, especially in hematologic malignancies. CTLA-4 and PD-1 are two important immune checkpoints negatively regulating T cell activation. Clinical benefits of CTLA-4/PD-1 antibodies are significant in melanoma and other solid tumors. PD-1 is predicted to have fewer side effects and greater antitumor activity than CTLA-4. In this review, we will summarize current immunotherapies based on CAR T cells and PD-1.

  4. M867, a novel selective inhibitor of caspase-3 enhances cell death and extends tumor growth delay in irradiated lung cancer models.

    Directory of Open Access Journals (Sweden)

    Kwang Woon Kim

    Full Text Available BACKGROUND: Lung cancer remains the leading cause of cancer death worldwide. Radioresistance of lung cancer cells results in unacceptable rate of loco-regional failure. Although radiation is known to induce apoptosis, our recent study showed that knockdown of pro-apoptotic proteins Bak and Bax resulted in an increase in autophagic cell death and lung cancer radiosensitivity in vitro. To further explore the potential of apoptosis inhibition as a way to sensitize lung cancer for therapy, we tested M867, a novel chemical and reversible caspase-3 inhibitor, in combination with ionizing radiation in vivo and in vitro. METHODS AND FINDINGS: M867 reduced clonogenic survival in H460 lung cancer cells (DER = 1.27, p = 0.007 compared to the vehicle-treated treated cells. We found that administration of M867 with ionizing radiation in an in vivo mouse hind limb lung cancer model was well tolerated, and produced a significant tumor growth delay compared to radiation alone. A dramatic decrease in tumor vasculature was observed with M867 and radiation using von Willebrand factor staining. In addition, Ki67 index showed >5-fold reduction of tumor proliferation in the combination therapy group, despite the reduced levels of apoptosis observed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. Radiosensitizing effect of M867 through inhibiting caspases was validated using caspase-3/-7 double-knockout (DKO mouse embryonic fibroblasts (MEF cell model. Consistent with our previous study, autophagy contributed to the mechanism of increased cell death, following inhibition of apoptosis. In addition, matrigel assay showed a decrease in in vitro endothelial tubule formation during the M867/radiation combination treatment. CONCLUSIONS: M867 enhances the cytotoxic effects of radiation on lung cancer and its vasculature both in vitro and in vivo. M867 has the potential to prolong tumor growth delay by inhibiting tumor proliferation

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

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Miran; Park, Mi Hee; Kollipara, Pushpa Saranya [College of Pharmacy and Medical Research Center, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763 (Korea, Republic of); An, Byeong Jun; Song, Ho Sueb [College of Oriental Medicine, Kyungwon University, San 65, Bokjeong-dong, Sujeong-gu, Seongnam, Gyeonggii 461-701 (Korea, Republic of); Han, Sang Bae [College of Pharmacy and Medical Research Center, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763 (Korea, Republic of); Kim, Jang Heub [Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Song, Min Jong, E-mail: bitsugar@catholic.ac.kr [Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, 505, Banpo-dong, Seocho-gu, Seoul 137-040 (Korea, Republic of); Hong, Jin Tae, E-mail: jinthong@chungbuk.ac.kr [College of Pharmacy and Medical Research Center, Chungbuk National University, 48, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763 (Korea, Republic of)

    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.

  6. 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)

    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.

  7. Photoacoustic spectral analysis to sense programmed erythrocyte cell death (eryptosis) for monitoring cancer response to treatment

    Science.gov (United States)

    Fadhel, Muhannad N.; Kibria, Fayruz; Kolios, Michael C.

    2016-03-01

    Many types of cancer therapies target the tumor microenvironment, causing biochemical and morphological changes in tissues. In therapies using ultrasound activated microbubbles, vascular collapse is typically reported. Red blood cells (RBCs) that leak out of the vasculature become exposed to the ceramide that is released from damaged endothelial cells. Ceramide can induce programmed cell death in RBCs (eryptosis), and is characterized by cell shrinkage, membrane blebbing and scrambling. Since the effect of eryptotic cells on generated photoacoustics (PA) signals has not been reported, we investigated the potential PA may have for cancer treatment monitoring by using PA spectral analysis to sense eryptosis. To induce eryptosis, C2-ceramide was added to RBC suspensions and that were incubated for 24 hours at 37°C. A control and ceramide-induced sample was imaged in a vessel phantom using a high frequency PA system (VevoLAZR, 10 - 45 MHz bandwidth) irradiated with multiple wavelengths ranging from 680 to 900 nm. PA spectral parameters were measured and linked to changes in RBCs as it underwent eryptosis. These samples were examined using optical microscopy, a blood gas analyzer and an integrating sphere setup to measure optical properties (wavelengths 600 - 900 nm). The results of the experiment demonstrate how PA spectral analysis can be used to identify eryptosis at a depth of more than 1 cm into the phantom using ultrasound derived the y-intercept and mid bandfit (MBF) parameters at optical wavelengths of 800 - 900 nm. These parameters were correlated to the morphological and biochemical changes that eryptotic RBCs display. The results establish the potential of PA in cancer treatment monitoring through sensing treatment induced eryptosis.

  8. Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1

    Directory of Open Access Journals (Sweden)

    Dong L

    2015-12-01

    Full Text Available Liwei Dong,1 Hongge Wang,1 Jiajing Niu,1 Mingwei Zou,2 Nuoting Wu,1 Debin Yu,1 Ye Wang,1 Zhihua Zou11Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Psychology, College of Liberal Arts and Social Sciences, University of Houston, Houston, TX, USA Abstract: Inhibition of the nucleotide pool sanitizing enzyme MTH1 causes extensive oxidative DNA damages and apoptosis in cancer cells and hence may be used as an anticancer strategy. As natural products have been a rich source of medicinal chemicals, in the present study, we used the MTH1-catalyzed enzymatic reaction as a high-throughput in vitro screening assay to search for natural compounds capable of inhibiting MTH1. Echinacoside, a compound derived from the medicinal plants Cistanche and Echinacea, effectively inhibited the catalytic activity of MTH1 in an in vitro assay. Treatment of various human cancer cell lines with Echinacoside resulted in a significant increase in the cellular level of oxidized guanine (8-oxoguanine, while cellular reactive oxygen species level remained unchanged, indicating that Echinacoside also inhibited the activity of cellular MTH1. Consequently, Echinacoside treatment induced an immediate and dramatic increase in DNA damage markers and upregulation of the G1/S-CDK inhibitor p21, which were followed by marked apoptotic cell death and cell cycle arrest in cancer but not in noncancer cells. Taken together, these studies identified a natural compound as an MTH1 inhibitor and suggest that natural products can be an important source of anticancer agents. Keywords: Echinacoside, MTH1, 8-oxoG, DNA damage, apoptosis, cell cycle arrest

  9. Circulating cell death products predict clinical outcome of colorectal cancer patients

    International Nuclear Information System (INIS)

    Tumor cell death generates products that can be measured in the circulation of cancer patients. CK18-Asp396 (M30 antigen) is a caspase-degraded product of cytokeratin 18 (CK18), produced by apoptotic epithelial cells, and is elevated in breast and lung cancer patients. We determined the CK18-Asp396 and total CK18 levels in plasma of 49 colorectal cancer patients, before and after surgical resection of the tumor, by ELISA. Correlations with patient and tumor characteristics were determined by Kruskal-Wallis H and Mann-Whitney U tests. Disease-free survival was determined using Kaplan-Meier methodology with Log Rank tests, and univariate and multivariate Cox proportional hazard analysis. Plasma CK18-Asp396 and total CK18 levels in colorectal cancer patients were related to disease stage and tumor diameter, and were predictive of disease-free survival, independent of disease-stage, with hazard ratios (HR) of patients with high levels (> median) compared to those with low levels (≤ median) of 3.58 (95% CI: 1.17–11.02) and 3.58 (95% CI: 0.97–7.71), respectively. The CK18-Asp396/CK18 ratio, which decreased with tumor progression, was also predictive of disease-free survival, with a low ratio (≤ median) associated with worse disease-free survival: HR 2.78 (95% CI: 1.06–7.19). Remarkably, the plasma CK18-Asp396 and total CK18 levels after surgical removal of the tumor were also predictive of disease-free survival, with patients with high levels having a HR of 3.78 (95% CI: 0.77–18.50) and 4.12 (95% CI: 0.84–20.34), respectively, indicating that these parameters can be used also to monitor patients after surgery. CK18-Asp396 and total CK18 levels in the circulation of colorectal cancer patients are predictive of tumor progression and prognosis and might be helpful for treatment selection and monitoring of these patients

  10. New steroidal aromatase inhibitors: Suppression of estrogen-dependent breast cancer cell proliferation and induction of cell death

    Directory of Open Access Journals (Sweden)

    Roleira Fernanda MF

    2008-07-01

    Full Text Available Abstract Background Aromatase, the cytochrome P-450 enzyme (CYP19 responsible for estrogen biosynthesis, is an important target for the treatment of estrogen-dependent breast cancer. In fact, the use of synthetic aromatase inhibitors (AI, which induce suppression of estrogen synthesis, has shown to be an effective alternative to the classical tamoxifen for the treatment of postmenopausal patients with ER-positive breast cancer. New AIs obtained, in our laboratory, by modification of the A and D-rings of the natural substrate of aromatase, compounds 3a and 4a, showed previously to efficiently suppress aromatase activity in placental microsomes. In the present study we have investigated the effects of these compounds on cell proliferation, cell cycle progression and induction of cell death using the estrogen-dependent human breast cancer cell line stably transfected with the aromatase gene, MCF-7 aro cells. Results The new steroids inhibit hormone-dependent proliferation of MCF-7aro cells in a time and dose-dependent manner, causing cell cycle arrest in G0/G1 phase and inducing cell death with features of apoptosis and autophagic cell death. Conclusion Our in vitro studies showed that the two steroidal AIs, 3a and 4a, are potent inhibitors of breast cancer cell proliferation. Moreover, it was also shown that the antiproliferative effects of these two steroids on MCF-7aro cells are mediated by disrupting cell cycle progression, through cell cycle arrest in G0/G1 phase and induction of cell death, being the dominant mechanism autophagic cell death. Our results are important for the elucidation of the cellular effects of steroidal AIs on breast cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  12. 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)

    Radioimmunotherapy with α-particle-emitting nuclides, such as213Bi, 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 213Bi-immunoconjugates. Human gastric cancer cells (HSC45-M2) expressing d9-E-cadherin were incubated with different levels of activity of 213Bi-d9MAb targeting d9-E-cadherin and 213Bi-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 213Bi-d9MAb. Activation of caspase 3 after incubation of HSC45-M2 cells with both sorbitol and 213Bi-d9MAb was analysed via Western blotting. Following incubation of HSC45-M2 human gastric cancer cells expressing d9-E-cadherin with 213Bi-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 213Bi-d9MAb compared with unspecific 213Bi-d8MAb (not targeting d9-E-cadherin) was not observed if the number of floating, i.e. unbound 213Bi-immunoconjugates per cell exceeded 2 x 104, most likely due to intense crossfire. In contrast to sorbitol-induced cell death, cell death triggered by 213Bi-immunoconjugates was independent of caspase 3 activation and could not be inhibited by z-VAD-fmk, known to suppress the apoptotic pathway. 213Bi-immunoconjugates seem to induce a mode of cell death different from apoptosis in HSC45-M2 cells. (orig.)

  13. Increasing Rates of Brain Tumours in the Swedish National Inpatient Register and the Causes of Death Register

    Directory of Open Access Journals (Sweden)

    Lennart Hardell

    2015-04-01

    Full Text Available Radiofrequency emissions in the frequency range 30 kHz–300 GHz were evaluated to be Group 2B, i.e., “possibly”, carcinogenic to humans by the International Agency for Research on Cancer (IARC at WHO in May 2011. The Swedish Cancer Register has not shown increasing incidence of brain tumours in recent years and has been used to dismiss epidemiological evidence on a risk. In this study we used the Swedish National Inpatient Register (IPR and Causes of Death Register (CDR to further study the incidence comparing with the Cancer Register data for the time period 1998–2013 using joinpoint regression analysis. In the IPR we found a joinpoint in 2007 with Annual Percentage Change (APC +4.25%, 95% CI +1.98, +6.57% during 2007–2013 for tumours of unknown type in the brain or CNS. In the CDR joinpoint regression found one joinpoint in 2008 with APC during 2008–2013 +22.60%, 95% CI +9.68, +37.03%. These tumour diagnoses would be based on clinical examination, mainly CT and/or MRI, but without histopathology or cytology. No statistically significant increasing incidence was found in the Swedish Cancer Register during these years. We postulate that a large part of brain tumours of unknown type are never reported to the Cancer Register. Furthermore, the frequency of diagnosis based on autopsy has declined substantially due to a general decline of autopsies in Sweden adding further to missing cases. We conclude that the Swedish Cancer Register is not reliable to be used to dismiss results in epidemiological studies on the use of wireless phones and brain tumour risk.

  14. Pneumocystis jirovecii Genotype Associated with Increased Death Rate of HIV-infected Patients with Pneumonia

    OpenAIRE

    Rabodonirina, Meja; VAILLANT Laetitia; Taffé, Patrick; Nahimana, Aimable; Gillibert, René-Pierre; Vanhems, Philippe; Hauser, Philippe M.

    2013-01-01

    Pneumocystis jirovecii dihydropteroate synthase (DHPS) mutations have been associated with failure of sulfa prophylaxis; their effect on the outcome of patients with P. jirovecii pneumonia (PCP) remains controversial. P. jirovecii DHPS polymorphisms and genotypes were identified in 112 cases of PCP in 110 HIV-infected patients by using PCR single-strand conformation polymorphism. Of the 110 patients observed, 21 died; 18 of those deaths were attributed to PCP. Thirty-three percent of the PCP ...

  15. The global decline in asthma death rates: can we relax now?

    OpenAIRE

    Rebuck, Anthony S.

    2013-01-01

    Whilst global asthma mortality seems to be decreasing, childhood asthma incidence is rising, and early warnings from Australia show an increase in asthma-related deaths in under-15s; this article considers whether we should view the future impact of asthma with trepidation. Age-adjusted mortality statistics for asthma have been reevaluated to provide an international standard. Comparisons across regions and time are complex, yet over the last two decades asthma mortality has clearly decreased...

  16. Inducing enhanced immunogenic cell death with nanocarrier-based drug delivery systems for pancreatic cancer therapy.

    Science.gov (United States)

    Zhao, Xiao; Yang, Keni; Zhao, Ruifang; Ji, Tianjiao; Wang, Xiuchao; Yang, Xiao; Zhang, Yinlong; Cheng, Keman; Liu, Shaoli; Hao, Jihui; Ren, He; Leong, Kam W; Nie, Guangjun

    2016-09-01

    Immunogenic cell death (ICD) occurs when apoptotic tumor cell elicits a specific immune response, which may trigger an anti-tumor effect, via the release of immunostimulatory damage-associated molecular patterns (DAMPs). Hypothesizing that nanomedicines may impact ICD due to their proven advantages in delivery of chemotherapeutics, we encapsulated oxaliplatin (OXA) or gemcitabine (GEM), an ICD and a non-ICD inducer respectively, into the amphiphilic diblock copolymer nanoparticles. Neither GEM nor nanoparticle-encapsulated GEM (NP-GEM) induced ICD, while both OXA and nanoparticle-encapsulated OXA (NP-OXA) induced ICD. Interestingly, NP-OXA treated tumor cells released more DAMPs and induced stronger immune responses of dendritic cells and T lymphocytes than OXA treatment in vitro. Furthermore, OXA and NP-OXA exhibited stronger therapeutic effects in immunocompetent mice than in immunodeficient mice, and the enhancement of therapeutic efficacy was significantly higher in the NP-OXA group than the OXA group. Moreover, NP-OXA treatment induced a higher proportion of tumor infiltrating activated cytotoxic T-lymphocytes than OXA treatment. This general trend of enhanced ICD by nanoparticle delivery was corroborated in evaluating another pair of ICD inducer and non-ICD inducer, doxorubicin and 5-fluorouracil. In conclusion, although nanoparticle encapsulation did not endow a non-ICD inducer with ICD-mediated anti-tumor capacity, treatment with a nanoparticle-encapsulated ICD inducer led to significantly enhanced ICD and consequently improved anti-tumor effects than the free ICD inducer. The proposed nanomedicine approach may impact cancer immunotherapy via the novel cell death mechanism of ICD. PMID:27343466

  17. The expression status and prognostic significance of programmed cell death 1 ligand 1 in gastro­intestinal tract cancer: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Huang B

    2015-09-01

    Full Text Available Baohua Huang,* Lei Chen,* Cuixia Bao, Chengming Sun, Jie Li, Lipeng Wang, Xia Zhang Department of Laboratory Medicine, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China *These authors contributed equally to this work Background: Programmed cell death 1 ligand 1 (PD-L1 expression has been observed in various malignancies. However, the association between PD-L1 expression and the survival of patients with gastrointestinal tract cancer remains controversial. Besides, the rate of PD-L1 positivity on tumor cells of digestive tract cancer is not clear. Thus, we performed a meta-analysis by incorporating all available evidence to evaluate the rate of PD-L1 positivity and the overall survival (OS according to PD-L1 status in patients with gastrointestinal tract cancer. Methods: Electronic databases were searched for eligible literature. Hazard ratios (HRs for OS with 95% confidence intervals (CIs according to the expression status of PD-L1 evaluated by immunohistochemistry were extracted. The outcomes were synthesized based on a random-effects model.Results: Fifteen studies (only nine reported OS that involved 2,993 gastrointestinal tract cancer patients stratified by PD-L1 status were eligible for inclusion in our study. We found the PD-L1-positive expression rate was 0.495 (95% CI 0.415–0.576 if 10% was taken as the cut-off value. When the H-score method was used to evaluate PD-L1 expression, it showed that the PD-L1 positive rate was 0.639 (95% CI 0.490–0.765 if the cut-off value was <50, which was higher than when using >50 as the cut-off point (0.449, 95% CI 0.417–0.483. Additionally, PD-L1-positive gastrointestinal tract cancer patients were associated with significantly poorer OS when compared to negative ones (HR 1.61, 95% CI 1.10–2.35, P=0.014. Subgroup analysis presented similar significant results in patients with esophageal cancer (HR 2.56, 95% CI 1.55–4.21, P<0.001. Conclusion: The positive expression rate of PD-L1

  18. An in vivo root hair assay for determining rates of apoptotic-like programmed cell death in plants

    Directory of Open Access Journals (Sweden)

    Hogg Bridget V

    2011-12-01

    Full Text Available Abstract In Arabidopsis thaliana we demonstrate that dying root hairs provide an easy and rapid in vivo model for the morphological identification of apoptotic-like programmed cell death (AL-PCD in plants. The model described here is transferable between species, can be used to investigate rates of AL-PCD in response to various treatments and to identify modulation of AL-PCD rates in mutant/transgenic plant lines facilitating rapid screening of mutant populations in order to identify genes involved in AL-PCD regulation.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y. M.; Hur, T. R.; Lee, K. B.; Jeong, M. H.; Park, J. W. [Kyungbook National Univ., Daegu (Korea, Republic of)

    2007-04-15

    Proton beam induced apoptosis significantly in Lewis lung carcinoma cells and hepatoma HepG2 cells in a dose- and time-dependent manner, but slightly in leukemia Molt-4 cells. Relative biological effectiveness (RBE) values for death rate relative to gamma ray were ranged from 1.3 to 2.1 in LLC or HepG2 but 0.7 in Molt-4 cells at 72h after irradiation. The typical apoptosis was observed by nuclear DNA staining with DAPI. By FACS analysis after stained with PI, sub-G1 cell fraction was significantly increased but G2/M phase was not altered by proton beam irradiation measured at 24 h after irradiation. Proton beam-irradiated tumor cells induced cleavage of PARP-1 and procaspases (-3 and -9) and increased the level of p53 and p21. decreased pro-lamin B. Acitivity of caspases was significantly increased after proton beam irradiation. Furthermore, ROS were significantly increased and N-acetyl cystein (NAC) pretreatment restored the apoptotic cell death induced in proton beam-irradiated cells. In conclusion, single treatment of low energy proton beam with SOBP induced apoptosis of solid tumor cells via increased ROS, active caspase -3,-9 and p53, p2.

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

    International Nuclear Information System (INIS)

    Proton beam induced apoptosis significantly in Lewis lung carcinoma cells and hepatoma HepG2 cells in a dose- and time-dependent manner, but slightly in leukemia Molt-4 cells. Relative biological effectiveness (RBE) values for death rate relative to gamma ray were ranged from 1.3 to 2.1 in LLC or HepG2 but 0.7 in Molt-4 cells at 72h after irradiation. The typical apoptosis was observed by nuclear DNA staining with DAPI. By FACS analysis after stained with PI, sub-G1 cell fraction was significantly increased but G2/M phase was not altered by proton beam irradiation measured at 24 h after irradiation. Proton beam-irradiated tumor cells induced cleavage of PARP-1 and procaspases (-3 and -9) and increased the level of p53 and p21. decreased pro-lamin B. Acitivity of caspases was significantly increased after proton beam irradiation. Furthermore, ROS were significantly increased and N-acetyl cystein (NAC) pretreatment restored the apoptotic cell death induced in proton beam-irradiated cells. In conclusion, single treatment of low energy proton beam with SOBP induced apoptosis of solid tumor cells via increased ROS, active caspase -3,-9 and p53, p2

  1. Surveillance of Caging and Poultry Separation Behavior in Relation Toward Poultry Death Rate Caused by Avian Influenza at Bandung District

    Directory of Open Access Journals (Sweden)

    L.B. Roostita

    2010-07-01

    Full Text Available There are four priorities i.e., report, cook, separate and wash for preventing Avian Influenza (A I virus transmission from poultry-to-poultry, poultry-to-animal, and poultry to human at the community level. Unfortunately, caging and separating poultry were still rarely performed by poultry owners at Indonesia. Therefore, survey of poultry caging and poultry separation conducted in Bandung district where highest incidence and prevalence of human cases of AI occur. The objectives of this survey were to determine how poultry death rate influenced by caging and poultry separation behaviors (separate between different species and ages, segregation during restocking. This research uses survey methods with household who kept poultry and household where sick or died poultry found as unit of analysis. Data obtained by in-depth interview by using the interview guidelines covering aspects: issues related to sick or death of poultry, caging habits, separation of different poultry species and age and also segregation during restocking. Result showed that poultry owners in the area by high poultry death rate; Panyirapan (13.19% and Soreang (9.52%; tend to free ranging the birds; Panyirapan (54.54%, Soreang (72.72%. In addition, only 9.09% poultry owners in Panyirapan doing separation between different species, age and segregation during restocking, while poultry owners in Soreang unfortunately never separate among them (0%.

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

    Science.gov (United States)

    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. PMID:15572295

  3. Reduced death rates from cyclones in Bangladesh: what more needs to be done?

    Directory of Open Access Journals (Sweden)

    Ubydul Haque

    2012-02-01

    Full Text Available Tropical storms, such as cyclones, hurricanes and typhoons, present major threats to coastal communities. Around two million people worldwide have died and millions have been injured over the past two centuries as a result of tropical storms. Bangladesh is especially vulnerable to tropical cyclones, with around 718 000 deaths from them in the past 50 years. However, cyclone-related mortality in Bangladesh has declined by more than 100-fold over the past 40 years, from 500 000 deaths in 1970 to 4234 in 2007. The main factors responsible for these reduced fatalities and injuries are improved defensive measures, including early warning systems, cyclone shelters, evacuation plans, coastal embankments, reforestation schemes and increased awareness and communication. Although warning systems have been improved, evacuation before a cyclone remains a challenge, with major problems caused by illiteracy, lack of awareness and poor communication. Despite the potential risks of climate change and tropical storms, little empirical knowledge exists on how to develop effective strategies to reduce or mitigate the effects of cyclones. This paper summarizes the most recent data and outlines the strategy adopted in Bangladesh. It offers guidance on how similar strategies can be adopted by other countries vulnerable to tropical storms. Further research is needed to enable countries to limit the risks that cyclones present to public health.

  4. Fragments of illness: The Death of a Beekeeper as a literary case study of cancer.

    Science.gov (United States)

    Bondevik, Hilde; Stene-Johansen, Knut; Ahlzén, Rolf

    2016-06-01

    The first decisive steps of medicine towards becoming a science in its present shape happen to coincide with "the rise of the novel" in the eighteenth century. Before this well known and in our days still growing scientific specialization of medicine, the connections between literature and medicine were both many and close. By reading and analyzing a contemporary novel, The Death of a Beekeeper by the Swedish author Lars Gustafsson (1978), this article is an attempt to explore to which extent a fictional narrative about a unique case of cancer may illuminate challenges associated with the experience of serious illness. Our claim is that medicine might draw wisdom from literature, its ability to create connections through narrative, to illuminate the complexity of ethical dilemmas, and to intertwine symptoms, life stories, and contexts. We argue that by being in the company of literary narratives and philosophical questions, physicians as well as other health care professionals may acquire clinically relevant skills which help them reach the ethically defined goals of their profession. PMID:26614116

  5. Increasing rates of surgical treatment and preventing comorbidities may increase breast cancer survival for Aboriginal women

    OpenAIRE

    Supramaniam, Rajah; Gibberd, Alison; Dillon, Anthony; Goldsbury, David Eamon; O’Connell, Dianne L

    2014-01-01

    Background Lower breast cancer survival has been reported for Australian Aboriginal women compared to non-Aboriginal women, however the reasons for this disparity have not been fully explored. We compared the surgical treatment and survival of Aboriginal and non-Aboriginal women diagnosed with breast cancer in New South Wales (NSW), Australia. Methods We analysed NSW cancer registry records of breast cancers diagnosed in 2001–2007, linked to hospital inpatient episodes and deaths. We used unc...

  6. The effects of burns and infusion therapy on the cell death rate in rabbit skin; in-vivo measurements of the cell death rate after marking with 5[125I]-iodo-2'-deoxyuridine

    International Nuclear Information System (INIS)

    The use of IDU marking of skin cells for the determination of the course of the skin cell cycle is confirmed. In the case of thermal trauma, however, an exact quantitative analysis of the cell death rate under the herein described conditions is no longer possible, because as a result of this thermal damage overlapping of various processes in the skin, for example circulation and transport disturbances, appears. The influence of an infusion treatment on the burned skin is therefore not measurable using the herein used skin cell marking. (orig.)

  7. Optical and Functional Imaging in Lung Cancer

    NARCIS (Netherlands)

    K.H. van der Leest (Cor)

    2010-01-01

    textabstractLung cancer is the second most common cancer in men and women, and is the leading cause of cancer related death. In industrialized countries the mortality rate of lung cancer is higher than the mortality rate of breast, colorectal and prostate cancer combined 1. When lung cancer is diagn

  8. High dose rate fractionated interstitial radiotherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nose, Takayuki; Inoue, Takehiro; Inoue, Toshihiko [Osaka Univ., Suita (Japan). Medical School] [and others

    1996-12-01

    From January 1993 through June 1996, thirteen advanced prostate cancer cases were treated with high dose rate interstitial radiotherapy using TRUS and perineal template guidance combined with or without external radiotherapy. Among eight cases eligible for local control, only one case relapsed so far. One perineal skin necrosis and one total incontinence were experienced in the patients treated with non-standard protocol dose. No apparent side effects were found in standard treatment patients. In addition with markedly increased tumor dose local control rate can be improved. (author)

  9. 广西肺癌死亡的流行特征及趋势%Epidemiological Characteristics and trends of deaths from lung cancer in Guangxi

    Institute of Scientific and Technical Information of China (English)

    邓伟; 黄天壬; 利基林; 余家华; 叶司原; 张春燕; 周信娟; 张振权; 何振芳; 周德南

    2012-01-01

    目的 描述2004~2005年广西肺癌的死亡率及流行特征,分析20世纪70年代~2005年广西肺癌的流行趋势.方法 采用多阶段分层抽样的方法选取广西9个县作为样本点,调查当地居民2004~2005年的死亡原因,分析肺癌死亡的流行特征.结果 2004 ~2005年广西肺癌的粗死亡率为24.54/10万(其中男性肺癌死亡率为33.66/10万,女性为14.48/10万).1964年中国人口标化率为13.58/10万.死亡率男女性别比为2.33∶1.肺癌占所有恶性肿瘤死亡的20.79%,居恶性肿瘤死亡的第2位.肺癌年龄别死亡率随着年龄的增长呈上升的趋势,大于40岁年龄组上升更为显著.2005年与20世纪70年代相比,肺癌标化率上升幅度达614.74%.结论 20世纪70年代~2005年这30年间,广西居民肺癌的死亡率呈上升的趋势,广西肺癌的防治研究任重面道远.%OBJECTIVE To describe the mortality and epidemiological characteristics of lung cancer in Guangxi between 2004 and 2005, and analyze the epidemiological trend from 1970's to 2005. METHODS Multi-stage stratified cluster random sampling method was used to select 9 counties in Guangxi as sample points. The residents' death causes between 2004 and 2005 were investigated, and the epidemiological characteristics of lung cancer were analyzed. RESULTS In the period of 2004-2005, the crude mortality of lung cancer was 24.54/100 000 in Guangxi population (33.66/100 000 in men and 14.48/100 000 in women). The national population-standardized mortality (NSM) in 1964 was 13.58/100 000. The man-to-woman ratio of mortality was 2.33:1. Lung cancer ranked as the second death cause among malignant tumors, and lung cancer-related death accounted for 20.79% of all tumor-related death cases. Age-specific mortality of lung cancer was increased with age, rising Bignif-icantly from 40-year-old. The national population-standardized mortality rates of lung cancer increased from 1.90/100 000 in 1970 's to 13.58/100 000 in

  10. Study of DNA damage and cell death rate in presence of gadolinium nanoparticles irradiated by fast atomic ions

    International Nuclear Information System (INIS)

    The goal of our work is to study the enhancement, and its mechanisms, of the cells death rate when they are loaded with high-Z atoms and irradiated by fast ions. Previous works have shown that cell death rate is increased by irradiation with atomic ions when molecules containing platinum are added in the cell. The choice of the radiosensitizer is and important guess. Ideally the radiosensitizer should target the tumour for hadrontherapy purpose. The nanoparticles, made of heavy atoms, offer the possibility to load the cells with high-Z atoms and when functionalized to target with a good selectivity the tissues of the tumour. In the present report we give the results obtained during 2010 with nanoparticules made of gadolinium atoms. The choice of these nanoparticles (NP-Gd) stem from the fact that they are made of a relatively high-Z atom (Z=64). A significant fraction of the isotope have a non zero spin allowing imaging by MRI. In addition the NP-Gd have been found non cytotoxic even at a large concentration (0.5 mM). Study of the number of DNA breaks in plasmids versus the concentration of the nanoparticles has been made. It is thus shown that the sensitization in nanoparticles is enhanced due to auto-amplified electronic cascades inside the nanoparticles, which reinforces the energy deposition in the close vicinity of the metal. The second part of this report presents the survival fraction of Chinese hamster ovary cells (CHO-K-1) cells incubated during 6 hours in a non-cytotoxic solution of NP-Gd. Subsequent irradiation by carbon ions 290 MeV/amu (linear energy transfer (LET)=13.6 keV/μm) was performed. A significant enhancement in the cell death rate is observed when nanoparticles are present. (author)

  11. The Growing Complexity of Cancer Cell Response to DNA-Damaging Agents: Caspase 3 Mediates Cell Death or Survival?

    OpenAIRE

    Razmik Mirzayans; Bonnie Andrais; Piyush Kumar; David Murray

    2016-01-01

    It is widely stated that wild-type p53 either mediates the activation of cell cycle checkpoints to facilitate DNA repair and promote cell survival, or orchestrates apoptotic cell death following exposure to cancer therapeutic agents. This reigning paradigm has been challenged by numerous discoveries with different human cell types, including solid tumor-derived cell lines. Thus, activation of the p53 signaling pathway by ionizing radiation and other DNA-damaging agents hinders apoptosis and t...

  12. Prognostic value of breast cancer subtypes on breast cancer specific survival, distant metastases and local relapse rates in conservatively managed early stage breast cancer: a retrospective clinical study

    OpenAIRE

    Sanpaolo, Pietro; Barbieri, Viviana; Genovesi, Domenico

    2011-01-01

    International audience To ascertain if breast cancer subtypes had prognostic effect on breast cancer specific survival, distant metastases and local relapse rates in women affected by early stage breast cancer.

  13. Cancer registries can provide evidence-based data to improve quality of care and prevent cancer deaths

    OpenAIRE

    Bouchardy Magnin, Christine; Rapiti Aylward, Elisabetta; Benhamou, Simone

    2014-01-01

    Today, many countries are increasing their efforts to ensure that all cancer patients receive the best possible care. Population-based cancer registries have adapted their registration to collect additional clinical variables to provide clinicians with unbiased population data on cancer treatment and survival. Taking several examples of epidemiological cancer research performed at the Geneva Cancer Registry, we aim to illustrate how cancer registries oversee the treatment and outcomes of canc...

  14. A receptor tyrosine kinase inhibitor, Tyrphostin A9 induces cancer cell death through Drp1 dependent mitochondria fragmentation

    International Nuclear Information System (INIS)

    Highlights: → We screened and identified Tyrphostin A9, a receptor tyrosine kinase inhibitor as a strong mitochondria fission inducer. → Tyrphostin A9 treatment promotes mitochondria dysfunction and contributes to cytotoxicity in cancer cells. → Tyrphostin A9 induces apoptotic cell death through a Drp1-mediated pathway. → Our studies suggest that Tyrphostin A9 induces mitochondria fragmentation and apoptotic cell death via Drp1 dependently. -- Abstract: Mitochondria dynamics controls not only their morphology but also functions of mitochondria. Therefore, an imbalance of the dynamics eventually leads to mitochondria disruption and cell death. To identify specific regulators of mitochondria dynamics, we screened a bioactive chemical compound library and selected Tyrphostin A9, a tyrosine kinase inhibitor, as a potent inducer of mitochondrial fission. Tyrphostin A9 treatment resulted in the formation of fragmented mitochondria filament. In addition, cellular ATP level was decreased and the mitochondrial membrane potential was collapsed in Tyr A9-treated cells. Suppression of Drp1 activity by siRNA or over-expression of a dominant negative mutant of Drp1 inhibited both mitochondrial fragmentation and cell death induced by Tyrpohotin A9. Moreover, treatment of Tyrphostin A9 also evoked mitochondrial fragmentation in other cells including the neuroblastomas. Taken together, these results suggest that Tyrphostin A9 induces Drp1-mediated mitochondrial fission and apoptotic cell death.

  15. A Review on Novel Breast Cancer Therapies: Photodynamic Therapy and Plant Derived Agent Induced Cell Death Mechanisms.

    Science.gov (United States)

    George, Blassan Plackal Adimuriyil; Abrahamse, Heidi

    2016-01-01

    This review article presents an extensive examination of risk factors for breast cancer, treatment strategies with special attention to photodynamic therapy and natural product based treatments. Breast cancer remains the most commonly occurring cancer in women worldwide and the detection, treatment, and prevention are prominent concerns in public health. Background information on current developments in treatment helps to update the approach towards risk assessment. Breast cancer risk is linked to many factors such as hereditary, reproductive and lifestyle factors. Minimally invasive Photodynamic therapy (PDT) can be used in the management of various cancers; it uses a light sensitive drug (a photosensitizer, PS) and a light of visible wavelength, to destroy targeted cancer cells. State of the art analyses has been carried out to investigate advancement in the search for the cure and control of cancer progression using natural products. Traditional medicinal plants have been used as lead compounds for drug discovery in modern medicine. Both PDT and plant derived drugs induce cell death via different mechanisms including apoptosis, necrosis, autophagy, cell cycle regulation and even the regulation of various cell signalling pathways. PMID:26499768

  16. 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.

  17. Death and Death Anxiety

    OpenAIRE

    Gonca Karakus; Zehra Ozturk; Lut Tamam

    2012-01-01

    Although death and life concepts seem so different from each other, some believe that death and life as a whole that death is accepted as the goal of life and death completes life. In different cultures, societies and disciplines, there have been very different definitions of death which changes according to personality, age, religion and cultural status of the individual. Attitudes towards death vary dramatically according to individuals. As for the death anxiety, it is a feeling which start...

  18. The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Cuezva José M

    2011-02-01

    Full Text Available Abstract Background Metabolic reprogramming resulting in enhanced glycolysis is a phenotypic trait of cancer cells, which is imposed by the tumor microenvironment and is linked to the down-regulation of the catalytic subunit of the mitochondrial H+-ATPase (β-F1-ATPase. The bioenergetic signature is a protein ratio (β-F1-ATPase/GAPDH, which provides an estimate of glucose metabolism in tumors and serves as a prognostic indicator for cancer patients. Targeting energetic metabolism could be a viable alternative to conventional anticancer chemotherapies. Herein, we document that the bioenergetic signature of isogenic colon cancer cells provides a gauge to predict the cell-death response to the metabolic inhibitors, 3-bromopyruvate (3BrP and iodoacetate (IA, and the anti-metabolite, 5-fluorouracil (5-FU. Methods The bioenergetic signature of the cells was determined by western blotting. Aerobic glycolysis was determined from lactate production rates. The cell death was analyzed by fluorescence microscopy and flow cytometry. Cellular ATP concentrations were determined using bioluminiscence. Pearson's correlation coefficient was applied to assess the relationship between the bioenergetic signature and the cell death response. In vivo tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells. Results We demonstrate that the bioenergetic signature of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely, the bioenergetic signature directly correlates with the potential to execute apoptosis in response to 5-FU treatment in the same cells. However, despite the large differences observed in the in vitro cell-death responses associated with 3BrP, IA and 5-FU, the in vivo tumor regression activities of these agents were comparable. Conclusions Overall, we suggest that the

  19. Air pollution in relation to US cancer mortality rates: an ecological study; likely role of carbonaceous aerosols and polycyclic aromatic hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Grant, W.B. [Sunlight Nutrients & Health Research Center SUNARC, San Francisco, CA (United States)

    2009-09-15

    There are large geographical variations of cancer mortality rates in the United States. In a series of ecological studies in the U.S., a number of risk-modifying factors including alcohol, diet, ethnic background, poverty, smoking, solar ultraviolet-B (UVB), and urban/rural residence have been linked to many types of cancer. Air pollution also plays a role in cancer risk. Cancer mortality rates averaged by state for two periods, 1950-1969 and 1970-1994, were used in multiple-linear regression analyses with respect to many, of the risk-modifying factors mentioned with the addition of an air pollution index in the form of a map of acid deposition in 1985. This index is correlated with emissions from coal-fired power plants. In addition, lung cancer mortality rates for five-Year periods from 1970-74 to 1990-94 were used in multiple linear regression analyses including air pollution and cigarette smoking. The air pollution index correlated with respiratory, digestive tract, urogenital, female, blood and skin cancer. Air pollution was estimated to account for 5% of male cancer deaths and 3% of female cancer deaths between 1970-1994. Solar UVB was inversely correlated with all these types of cancer except the respirator, skin and cervical cancer. Cigarette smoking was directly linked to lung cancer but not to other types of cancer in this study. Combustion of coal, diesel fuel and wood is the likely source of air pollution that affects cancer risk on a large scale, through production of black carbon aerosols with adsorbed polycyclic aromatic hydrocarbons.

  20. Effect of marital status on death rates. Part 1: High accuracy exploration of the Farr-Bertillon effect

    CERN Document Server

    Richmond, Peter

    2015-01-01

    The Farr-Bertillon law says that for all age-groups the death rate of married people is lower than the death rate of people who are not married (i.e. single, widowed or divorced). Although this law has been known for over 150 years, it has never been established with great accuracy. This even let some authors argue that it was a statistical artefact. It is true that the data must be selected and analyzed with great care, especially for age groups of small size such as widowers under 25. The observations reported in this paper were selected and designed in the same way as experiments in physics, that is to say with the objective of minimizing the error bars for all age-groups. It will be seen that data appropriate for mid-age groups may be unsuitable for young age groups and vice versa. The investigation led to the following results. (1) The FB effect is basically the same for men and women, except that on average it is about 20\\% stronger for men. (2) There is a marked difference between single or divorced pe...

  1. Coupling Between Blood Pressure And Heart Rate as Markers of Sudden Cardiac Death

    Czech Academy of Sciences Publication Activity Database

    Halámek, Josef; Jurák, Pavel; Kára, T.; Nykodým, J.; Eisenberger, M.; Souček, M.

    Brno : Brno University of Technology, 2004, s. 352-354. ISBN 80-214-2633-0. ISSN 1211-412X. [Biosignal 2004 /17./. Brno (CZ), 23.06.2004-25.06.2004] R&D Projects: GA ČR GA102/02/1339 Keywords : heart rate * systolic blood pressure * cardioverterdefibrilator Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

  2. Down-regulation of phosphoglucomutase 3 mediates sulforaphane-induced cell death in LNCaP prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Lee Hyo-Jeong

    2010-12-01

    Full Text Available Abstract Background Sulforaphane (SFN is an isothiocyanate found in cruciferous vegetables that exerts anti-oxidant, anti-inflammatory, anti-cancer and radio-sensitizing activities. Nonetheless, the mechanism responsible for SFN-induced cell death is not fully understood. In the present study, anti-cancer mechanism of SFN was elucidated in LNCaP prostate cancer cells. Results SFN exerted cytotoxicity and increased TUNEL positive cells in a concentration-dependent manner in LNCaP cells. Proteomics study revealed that levels of nine proteins including tubulin β-2, phosphoglucomutase-3 (PGM3, melanoma-derived leucine zipper containing extra-nuclear factor, activin A type I receptor precursor, smoothelin-A, KIA0073, hypothetical protein LOC57691 and two unnamed proteins were changed over 8 folds in SFN treated LNCaP cells compared to untreated control. We have further confirmed that SFN reduced PGM3 expression with western blotting and showed that PGM3 siRNA enhanced cytotoxicity demonstrated by cell morphology and TUNEL assays in LNCaP cells. Conclusion Taken together, these findings suggest that PGM3 plays a role in mediating SFN-induced cell death in LNCaP cells, and is a potential molecular therapeutic target for prostate cancer.

  3. Treatment-related death in patients with small-cell lung cancer in phase III trials over the last two decades.

    Directory of Open Access Journals (Sweden)

    Nobuaki Ochi

    Full Text Available INTRODUCTION: Treatment-related death (TRD remains a serious problem in small-cell lung cancer (SCLC, despite recent improvements in supportive care. However, few studies have formally assessed time trends in the proportion of TRD over the past two decades. The aim of this study was to determine the frequency and pattern of TRD over time. METHODS: We examined phase 3 trials conducted between 1990 and 2010 to address the role of systemic treatment for SCLC. The time trend was assessed using linear regression analysis. RESULTS: In total, 97 trials including nearly 25,000 enrolled patients were analyzed. The overall TRD proportion was 2.95%. Regarding the time trend, while it was not statistically significant, it tended to decrease, with a 0.138% decrease per year and 2.76% decrease per two decades. The most common cause of death was febrile neutropenia without any significant time trend in its incidence over the years examined (p = 0.139. However, deaths due to febrile neutropenia as well as all causes in patients treated with non-platinum chemotherapy increased significantly (p = 0.033. CONCLUSIONS: The overall TRD rate has been low, but not negligible, in phase III trials for SCLC over the past two decades.

  4. Premenopausal Obesity and Breast Cancer Growth Rates in a Rodent Model.

    Science.gov (United States)

    Matthews, Shawna B; McGinley, John N; Neil, Elizabeth S; Thompson, Henry J

    2016-01-01

    Obese premenopausal women with breast cancer have poorer prognosis for long term survival, in part because their tumors are larger at the time of diagnosis than are found in normal weight women. Whether larger tumor mass is due to obesity-related barriers to detection or to effects on tumor biology is not known. This study used polygenic models for obesity and breast cancer to deconstruct this question with the objective of determining whether cell autonomous mechanisms contribute to the link between obesity and breast cancer burden. Assessment of the growth rates of 259 chemically induced mammary carcinomas from rats sensitive to dietary induced obesity (DS) and of 143 carcinomas from rats resistant (DR) to dietary induced obesity revealed that tumors in DS rats grew 1.8 times faster than in DR rats. This difference may be attributed to alterations in cell cycle machinery that permit more rapid tumor cell accumulation. DS tumors displayed protein expression patterns consistent with reduced G1/S checkpoint inhibition and a higher threshold of factors required for execution of the apoptotic cell death pathway. These mechanistic insights identify regulatory targets for life style modifications or pharmacological interventions designed to disrupt the linkage between obesity and tumor burden. PMID:27077880

  5. Medium-dose-rate intracavitary brachytherapy for cervical cancer

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the results of medium-dose-rate (MDR) intracavitary brachytherapy (ICRT) for cervical cancer. Between May 1991 and March 2001, 80 patients with cervical cancer were treated with external radiotherapy combined with MDR-ICRT. Two patients were excluded from this study. The median age of patients was 61 years (range: 30-87 years). Seventy-five patients had pathologically proved squamous cell carcinoma, and 3 had adenocarcinoma. The patients were staged by Union Internationale Contre le Cancer (UICC) classification as follows: Stage IA (2), Stage IB (4), Stage IIA (5), Stage IIB (22), Stage IIIA (1), Stage IIIB (32), Stage IVA (5), Stage IVB (7). Median follow-up for survivor was 68 months (range: 12-131 months). The radiation therapy was based on a combination of ICRT and external pelvic irradiation. Patients with stages II, III and IVA were treated with whole-pelvic irradiation with respective total doses of 20, 30, and 40 Gy. Doses of 40, 30, 20, and 20 Gy parametrial irradiation were added with central shield pelvic irradiation for stages IB, II, III and IVA lesions respectively. For MDR-ICRT, from May 1991 to December 1995, point A dose were 40 Gy/4 fractions for stages I and II, 38 Gy/4 fractions for stage III, and 28.5 Gy/3 fractions for stage IVA. And from January 1996 to March 2001, point A dose of 36 Gy/4 fractions for stages I and II, 34 Gy/4 fractions for stage III, and 25.5 Gy/3 fractions for stage IVA. The median dose rate at point A was 1.7 Gy/hour (range: 1.3-2.2 Gy/hour). The 5-year cause-specific survival rates were 100%, 76%, 51% and 40% for stages I, II, III and IVA respectively. All patients with stage IVB died from the tumor with a median survival time of 12 months. The 5-year pelvic control rates were 100%, 88%, 69% and 40% for stages I, II, III and IVA respectively. Major late complications occurred in 2 patients (3%). One patient developed vesico- and recto-vaginal fistulae, and died of pelvic infection

  6. Heat-Modified Citrus Pectin Induces Apoptosis-Like Cell Death and Autophagy in HepG2 and A549 Cancer Cells

    OpenAIRE

    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...

  7. Accuracy of Death Certificates and Assessment of Factors for Misclassification of Underlying Cause of Death

    OpenAIRE

    Makiko Naka Mieno

    2016-01-01

    Background: Cause of death (COD) information taken from death certificates is often inaccurate and incomplete. However, the accuracy of Underlying CODs (UCODs) recorded on death certificates has not been comprehensively described when multiple diseases are present. Methods: A total of 450 consecutive autopsies performed at a geriatric hospital in Japan between February 2000 and August 2002 were studied. We evaluated the concordance rate, sensitivity, and specificity of major UCODs (cancer,...

  8. The DNA damage-induced cell death response: a roadmap to kill cancer cells.

    Science.gov (United States)

    Matt, Sonja; Hofmann, Thomas G

    2016-08-01

    Upon massive DNA damage cells fail to undergo productive DNA repair and trigger the cell death response. Resistance to cell death is linked to cellular transformation and carcinogenesis as well as radio- and chemoresistance, making the underlying signaling pathways a promising target for therapeutic intervention. Diverse DNA damage-induced cell death pathways are operative in mammalian cells and finally culminate in the induction of programmed cell death via activation of apoptosis or necroptosis. These signaling routes affect nuclear, mitochondria- and plasma membrane-associated key molecules to activate the apoptotic or necroptotic response. In this review, we highlight the main signaling pathways, molecular players and mechanisms guiding the DNA damage-induced cell death response. PMID:26791483

  9. A project for increasing the rate of participation in mammographic breast cancer screening in Kyoto prefecture to 50%

    International Nuclear Information System (INIS)

    The rate of participation in breast cancer screening carried out by inspection and palpation associated with mammography in Kyoto Prefecture has been still low. In order to decrease the rate of breast cancer death, a high rate of screening participation must be achieved. We have organized the Kyoto Executive Committee of Pink Ribbon Activity aiming at the goal of achieving a 50% rate of participation in mammography screening by the end of 2010, and undertaken the following campaign activities: performing free screening, distribution and display of posters and leaflets about breast cancer screening, cooperation with various media to spread educational and informative messages, cooperation with a commercial institute in Kyoto City to distribute useful information, performing free breast cancer screening, and holding public lecture meetings, distribution of leaflets at student festivals at universities and colleges in Kyoto, and holding a ''Pink Ribbon symposium'' in a cosponsored company. All the above projects were performed successfully and many participants attended. We will continue these activities until the 50% participation rate is achieved. (author)

  10. On the edge of death: Rates of decline and lower thresholds of biochemical condition in food-deprived fish larvae and juveniles

    DEFF Research Database (Denmark)

    Meyer, Stefan; Caldarone, E.M.; Chicharo, M.A.; Clemmensen, C.; Faria, A.M.; Faulk, C.; Folkvord, A.; Holt, G.J.; Høie, H.; Mahlzahn, A.; Moran, D.; Petereit, C.; Støttrup, Josianne; Peck, M.A.

    2012-01-01

    versus time (degree-days, Dd). The 10th percentile of sRD successfully approximated the lowest, life-stage-specific biochemical condition (the edge of death). Temperature could explain 59% of the variability in time to death whereas DW had no effect. Species and life-stage-specific differences in...... starvation parameters suggest selective adaptation to food deprivation. Previously published, interspecific functions predicting the relationship between growth rate and sRD in feeding fish larvae do not apply to individuals experiencing prolonged food deprivation. Starvation rate, edge of death, and time to...

  11. The Effect of Early Detection of Occult Brain Metastases in HER2-Positive Breast Cancer Patients on Survival and Cause of Death

    International Nuclear Information System (INIS)

    Purpose: The aim of the study is to evaluate disease-free survival, survival from the detection of brain metastases, overall survival, and cause of death in patients with occult brain metastases (Group I) vs. patients with symptomatic brain metastases (Group II). Methods and Materials: In 80 HER2-positive breast cancer patients, treated with trastuzumab and cytostatic agents for metastatic disease, magnetic resonance imaging screening of the brain was performed, and in 29 patients (36%) occult brain metastasis was detected (Group I). Whole-brain radiotherapy was delivered to Group I. This first group was compared with 52 patients who had symptomatic brain metastases (Group II) and was treated the same way, at the same clinic, during the same time period. Results: Median disease-free survival was 17 months in Group I and 19.9 months in Group II (p = 0.58). The median time interval between the dissemination of the disease and the detection of occult or symptomatic brain metastases was 9 and 15 months, respectively (p = 0.11). When the brain metastases were detected, the median survival was 9 and 8.78 months, respectively (p = 0.80). The median overall survival was 53 and 51 months, respectively (p = 0.94). In the group with occult brain metastases (Group I) 16% of patients died because of progression within the brain. In the group with symptomatic brain metastases (Group II) the rate of cerebral death was 48% (p = 0.009). Conclusions: Whole-brain radiotherapy of occult brain metastases in HER2-positive breast cancer patients with visceral dissemination produces a three-fold decrease in cerebral deaths but does not prolong survival.

  12. Denaturation of DNA repair proteins as a possible rate limiting step in the thermal death of single cells

    International Nuclear Information System (INIS)

    The experiments to be described support the hypothesis that the denaturation of DNA repair proteins is a rate limiting step in the thermal death of cells grown in tissue culture. Mammalian fibroblasts were subjected to small changes in temperature before ultraviolet (uv) irradiation in order to detect changes in repair of uv induced damage. Repair of DNA was measured by several methods after uv treatment. In some experiments repair was measured by incorporating 3H-Thymidine at 370C for different lengths of time after uv irradiation. Autoradiography suggested that prior heat treatment impairs the repair in all of the cells rather than causes the thermal death of a large portion of the cells. Finally, an endonuclease specific assay was conducted to determine whether the effects were due to the thermal denaturation of the endonuclease repair enzyme or rather to some heat sensitive process. By using a dimer specific endonuclease from M. luteus, the number of dimers produced and repaired was measured directly. For both hamster ahd human fibroblasts, significantly less repair was observed in cells incubated at 410C prior to uv treatment than in cells incubated at 370C before uv treatment. This suggests that the endonuclease repair enzymes are denatured at the higher temperature

  13. 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

  14. TRAIL-induced apoptosis and expression of death receptor TRAIL-R1 and TRAIL-R2 in bladder cancer cells.

    Directory of Open Access Journals (Sweden)

    Zenon P Czuba

    2010-05-01

    Full Text Available Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L is a member of TNF superfamily able to induce programmed death in cancer cells with no toxicity against normal tissues. TRAIL mediate apoptosis follows binding to the two death receptors, TRAIL-R1 (DR4 and/or TRAIL-R2 (DR5. In this study we investigated the cytotoxic and apoptotic effect of TRAIL on bladder cancer cells and the expression of death receptor TRAIL-R1 and TRAIL-R2 on the surface of these cancer cells. Three human bladder transitional cancer cell (TCC lines - SW780, 647V and T24 were tested for TRAIL sensitivity. The bladder cancer cells were incubated with human soluble recombinant TRAIL. Cytotoxicity was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-dimethyltetrazolium bromide and LDH (lactate dyhydrogenase assays. Apoptosis was detected by flow cytometry with annexin V-FITC/propidium iodide and by fluorescence microscopy with Hoechst 33342/annexin V-FITC/Ethidium Homodimer. The cell surface expression of TRAIL death receptors on bladder cancer were determined using flow cytometry with phycoerythrin-conjugated monoclonal anti-human TRAIL-R1 and TRAIL-R2. Our investigations confirmed that SW780 cells were sensitive to TRAIL, and two other bladder cancer cell lines, 647V and T24, were resistant to TRAIL induced apoptosis. We therefore examined the expression of TRAIL death receptors on bladder cancer cell surfaces. We showed decreased expression of TRAIL-R2 receptor in TRAIL-resistant bladder cancer cells and increased expression of this death receptor in TRAIL-sensitive SW780 cells. The expression of TRAILR1 receptor was similar in all bladder cancer cell lines. TRAIL is one of the promising candidates for cancer therapeutics. However, some cancer cells are resistant to TRAIL-mediated apoptosis. It is therefore important to overcome this resistance for the clinical use of TRAIL in cancer therapy. TRAIL death receptors are attractive therapeutic targets in

  15. An International Comparison of Male and Female Breast Cancer Incidence Rates

    OpenAIRE

    Ly, Diana; Forman, David; Ferlay, Jacques; Brinton, Louise A.; Cook, Michael B.

    2012-01-01

    Global international trends in female breast cancer incidence have been described previously but no comparable analysis of male breast cancer incidence rates has been conducted. We obtained male and female case and population data using Cancer Incidence in Five Continents (CI5). We calculated age-adjusted sex-specific incidence rates and female-to-male incidence rate ratios (FMIRRs) and compared trends of such for the period 1988–2002. This analysis included 8,681 male breast cancer cases and...

  16. TRAIL Death Receptor-4 Expression Positively Correlates With the Tumor Grade in Breast Cancer Patients With Invasive Ductal Carcinoma

    International Nuclear Information System (INIS)

    Purpose: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells, and a number of clinical trials have recently been initiated to test the safety and antitumoral potential of TRAIL in cancer patients. Four different receptors have been identified to interact with TRAIL: two are death-inducing receptors (TRAIL-R1 [DR4] and TRAIL-R2 [DR5]), whereas the other two (TRAIL-R3 [DcR1] and TRAIL-R4 [DcR2]) do not induce death upon ligation and are believed to counteract TRAIL-induced cytotoxicity. Because high levels of DcR2 expression have recently been correlated with carcinogenesis in the prostate and lung, this study investigated the importance of TRAIL and TRAIL receptor expression in breast cancer patients with invasive ductal carcinoma, taking various prognostic markers into consideration. Methods and Materials: Immunohistochemical analyses were performed on 90 breast cancer patients with invasive ductal carcinoma using TRAIL and TRAIL receptor-specific antibodies. Age, menopausal status, tumor size, lymph node status, tumor grade, lymphovascular invasion, perineural invasion, extracapsular tumor extension, presence of an extensive intraductal component, multicentricity, estrogen and progesterone receptor status, and CerbB2 expression levels were analyzed with respect to TRAIL/TRAIL receptor expression patterns. Results: The highest TRAIL receptor expressed in patients with invasive ductal carcinoma was DR4. Although progesterone receptor-positive patients exhibited lower DR5 expression, CerbB2-positive tissues displayed higher levels of both DR5 and TRAIL expressions. Conclusions: DR4 expression positively correlates with the tumor grade in breast cancer patients with invasive ductal carcinoma

  17. 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; Sørensen, Vibeke Rømming

    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, the...

  18. Synergistic chemopreventive effects of curcumin and berberine on human breast cancer cells through induction of apoptosis and autophagic cell death.

    Science.gov (United States)

    Wang, Kai; Zhang, Chao; Bao, Jiaolin; Jia, Xuejing; Liang, Yeer; Wang, Xiaotong; Chen, Meiwan; Su, Huanxing; Li, Peng; Wan, Jian-Bo; He, Chengwei

    2016-01-01

    Curcumin (CUR) and berberine (BBR) are renowned natural compounds that exhibit potent anticancer activities through distinct molecular mechanisms. However, the anticancer capacity of either CUR or BBR is limited. This prompted us to investigate the chemopreventive potential of co-treatment of CUR and BBR against breast cancers. The results showed that CUR and BBR in combination synergistically inhibited the growth of both MCF-7 and MDA-MB-231 breast cancer cells than the compounds used alone. Further study confirmed that synergistic anti-breast cancer activities of co-treatment of these two compounds was through inducing more apoptosis and autophagic cell death (ACD). The co-treatment-induced apoptosis was caspase-dependent and through activating ERK pathways. Our data also demonstrated that co-treatment of CUR and BBR strongly up-regulated phosphorylation of JNK and Beclin1, and decreased phosphorylated Bcl-2. Inhibition of JNK by SP600125 markedly decreased LC3-II and Beclin1, restored phosphorylated Bcl-2, and reduced the cytotoxicity induced by the two compounds in combination. These results strongly suggested that JNK/Bcl-2/Beclin1 pathway played a key role in the induction of ACD in breast cancer cells by co-treatment of CUR and BBR. This study provides an insight into the potential application of curcumin and berberine in combination for the chemoprevention and treatment of breast cancers. PMID:27263652

  19. Older Age Predicts Decreased Metastasis and Prostate Cancer-Specific Death for Men Treated With Radiation Therapy: Meta-Analysis of Radiation Therapy Oncology Group Trials

    International Nuclear Information System (INIS)

    Purpose: The impact of age on prostate cancer (PCa) outcome has been controversial; therefore, we analyzed the effect of age on overall survival (OS), distant metastasis, prostate cancer-specific death (PCSD), and nonprostate cancer death (NPCD) on patients with locally advanced PCa. Methods and Materials: Patients who participated in four Radiation Therapy Oncology Group (RTOG) phase III trials, 8531, 8610, 9202, and 9413, were studied. Cox proportional hazards regression was used for OS analysis, and cumulative events analysis with Fine and Gray’s regression was used for analyses of metastasis, PCSD, and NPCD. Results: Median follow-up of 4,128 patients with median age of 70 (range, 43-88 years) was 7.3 years. Most patients had high-risk disease: cT3 to cT4 (54%) and Gleason scores (GS) of 7 (45%) and 8 to 10 (27%). Older age (≤70 vs. >70 years) predicted for decreased OS (10-year rate, 55% vs. 41%, respectively; p 70 years remained associated with decreased OS (hazard ratio [HR], 1.56 [95% confidence interval [CI], 1.43-1.70] p < 0.0001) but with decreased metastasis (HR, 0.72 [95% CI, 0.63-0.83] p < 0.0001) and PCSD (HR, 0.78 [95% CI, 0.66-0.92] p < 0.0001). Finally, the impact of the duration of androgen deprivation therapy as a function of age was evaluated. Conclusions: These data support less aggressive PCa in older men, independent of other clinical features. While the biological underpinning of this finding remains unknown, stratification by age in future trials appears to be warranted.

  20. 3-Bromopyruvate induces rapid human prostate cancer cell death by affecting cell energy metabolism, GSH pool and the glyoxalase system.

    Science.gov (United States)

    Valenti, Daniela; Vacca, Rosa A; de Bari, Lidia

    2015-12-01

    3-bromopyruvate (3-BP) is an anti-tumour drug effective on hepatocellular carcinoma and other tumour cell types, which affects both glycolytic and mitochondrial targets, depleting cellular ATP pool. Here we tested 3-BP on human prostate cancer cells showing, differently from other tumour types, efficient ATP production and functional mitochondrial metabolism. We found that 3-BP rapidly induced cultured androgen-insensitive (PC-3) and androgen-responsive (LNCaP) prostate cancer cell death at low concentrations (IC(50) values of 50 and 70 μM, respectively) with a multimodal mechanism of action. In particular, 3-BP-treated PC-3 cells showed a selective, strong reduction of glyceraldeide 3-phosphate dehydrogenase activity, due to the direct interaction of the drug with the enzyme. Moreover, 3-BP strongly impaired both glutamate/malate- and succinate-dependent mitochondrial respiration, membrane potential generation and ATP synthesis, concomitant with the inhibition of respiratory chain complex I, II and ATP synthase activities. The drastic reduction of cellular ATP levels and depletion of GSH pool, associated with significant increase in cell oxidative stress, were found after 3-BP treatment of PC-3 cells. Interestingly, the activity of both glyoxalase I and II, devoted to the elimination of the cytotoxic methylglyoxal, was strongly inhibited by 3-BP. Both N-acetylcysteine and aminoguanidine, GSH precursor and methylglyoxal scavenger, respectively, prevented 3-BP-induced PC-3 cell death, showing that impaired cell antioxidant and detoxifying capacities are crucial events leading to cell death. The provided information on the multi-target cytotoxic action of 3-BP, finally leading to PC-3 cell necrosis, might be useful for future development of 3-BP as a therapeutic option for prostate cancer treatment. PMID:26530987

  1. Brachytherapy for early oral tongue cancer. Low dose rate to high dose rate

    International Nuclear Information System (INIS)

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n=341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer. (author)

  2. Predictors of dying at home for patients receiving nursing services in Japan: A retrospective study comparing cancer and non-cancer deaths

    Directory of Open Access Journals (Sweden)

    Ikegami Naoki

    2011-03-01

    Full Text Available Abstract Background The combined effects of the patient's and the family's preferences for death at home have in determining the actual site of death has not been fully investigated. We explored this issue on patients who had been receiving end-of-life care from Visiting Nurse Stations (VNS. In Japan, it has been the government's policy to promote end-of-life care at home by expanding the use of VNS services. Methods A retrospective national survey of a random sample of 2,000 out of the 5,224 VNS was made in January 2005. Questionnaires were mailed to VNS asking the respondents to fill in the questionnaire for each patient who had died either at home or at the hospital from July to December of 2004. Logistic regression analysis was respectively carried out to examine the factors related to dying at home for cancer and non-cancer patients. Results We obtained valid responses from 1,016 VNS (50.8%. The total number of patients who had died in the selected period was 4,175 (cancer: 1,664; non-cancer: 2,511. Compared to cancer patients, non-cancer patients were older and had more impairment in activities of daily living (ADL and cognitive performance, and a longer duration of care. The factor having the greatest impact for dying at home was that of both the patient and the family expressing such preferences [cancer: OR (95% CI = 57.00 (38.79-83.76; non-cancer: OR (95% CI = 12.33 (9.51-15.99]. The Odds ratio was greater compared with cases in which only the family had expressed such a preference and in which only the patient had expressed such a preference. ADL or cognitive impairment and the fact that their physician was based at a clinic, and not at a hospital, had modest effects on dying at home. Conclusions Dying at home was more likely when both the patient and the family had expressed such preferences, than when the patient alone or the family alone had done so, in both cancer and non-cancer patients. Health care professionals should try to

  3. Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and -independent mechanisms

    Institute of Scientific and Technical Information of China (English)

    Ying-jia ZHONG; Yong QIN; Lin-chuan; LIAO Xia WANG; Fang SHI; Xue-lian ZHENG; Qiong WANG; Lan YANG; Hong SUN; Fan HE; Lin ZHANG; Yong LIN

    2011-01-01

    To investigate the anticancer effect of crocetin,a major ingredient in saffron,and its underlying mechanisms.Methods:Cervical cancer cell line HeLa,non-small cell lung cancer cell line A549 and ovarian cancer cell line SKOV3 were treated with crocetin alone or in combination with vincristine.Cell proliferation was examined using MTT assay.Cell cycle distribution and sub-G1 fraction were analyzed using flow cytometric analysis after propidium iodide staining.Apoptosis was detected using the Annexin V-FITC Apoptosis Detection Kit with flow cytometry.Cell death was measured based on the release of lactate dehydrogenase (LDH).The expression levels of p53 and p21wAF1/Cip1 as well as caspase activation were examined using Western blot analysis.Results:Treatment of the 3 types of cancer cells with crocetin (60-240 μmol/L) for 48 h significantly inhibited their proliferation in a concentration-dependent manner.Crocetin (240 μmol/L) significantly induced cell cycle arrest through p53-dependent and -independent mechanisms accompanied with p21WAF1/Cip1 induction.Crocetin (120-240 μmoVL) caused cytotoxicity in the 3 types of cancer cells by enhancing apoptosis in a time-dependent manner.In the 3 types of cancer cells,crocetin (60 μmol/L) significantly enhanced the cytotoxicity induced by vincristine (1 μmol/L).Furthermore,this synergistic effect was also detected in the vincristine-resistant breast cancer cell line MCF-7/VCR.Conclusion:Ccrocetin is a potential anticancer agent,which may be used as a chemotherapeutic drug or as a chemosensitizer for vin-cristine.

  4. High lung cancer surgical procedure volume is associated with shorter length of stay and lower risks of re-admission and death: National cohort analysis in England.

    Science.gov (United States)

    Møller, Henrik; Riaz, Sharma P; Holmberg, Lars; Jakobsen, Erik; Lagergren, Jesper; Page, Richard; Peake, Michael D; Pearce, Neil; Purushotham, Arnie; Sullivan, Richard; Vedsted, Peter; Luchtenborg, Margreet

    2016-09-01

    It is debated whether treating cancer patients in high-volume surgical centres can lead to improvement in outcomes, such as shorter length of hospital stay, decreased frequency and severity of post-operative complications, decreased re-admission, and decreased mortality. The dataset for this analysis was based on cancer registration and hospital discharge data and comprised information on 15,738 non-small-cell lung cancer patients resident and diagnosed in England in 2006-2010 and treated by surgical resection. The number of lung cancer resections was computed for each hospital in each calendar year, and patients were assigned to a hospital volume quintile on the basis of the volume of their hospital. Hospitals with large lung cancer surgical resection volumes were less restrictive in their selection of patients for surgical management and provided a higher resection rate to their geographical population. Higher volume hospitals had shorter length of stay and the odds of re-admission were 15% lower in the highest hospital volume quintile compared with the lowest quintile. Mortality risks were 1% after 30 d and 3% after 90 d. Patients from hospitals in the highest volume quintile had about half the odds of death within 30 d than patients from the lowest quintile. Variations in outcomes were generally small, but in the same direction, with consistently better outcomes in the larger hospitals. This gives support to the ongoing trend towards centralisation of clinical services, but service re-organisation needs to take account of not only the size of hospitals but also referral routes and patient access. PMID:27328450

  5. Diabetes, metformin and incidence of and death from invasive cancer in postmenopausal women: Results from the women’s health initiative

    Science.gov (United States)

    Gong, Zhihong; Aragaki, Aaron K.; Chlebowski, Rowan T.; Manson, JoAnn E.; Rohan, Thomas E.; Chen, Chu; Vitolins, Mara Z.; Tinker, Lesley F.; LeBlanc, Erin S.; Kuller, Lewis H.; Hou, Lifang; LaMonte, Michael J.; Luo, Juhua; Wactawski-Wende, Jean

    2016-01-01

    Findings from studies of metformin use with risk of cancer incidence and outcome provide mixed results; with few studies examined associations by recency of diabetes diagnosis or duration of medication use. Thus, in the Women’s Health Initiative, we examined these associations and further explored whether associations differ by recency of diabetes and duration of metformin use. Cox regression models were used to estimate hazard ratios (HR) and their 95% confidence intervals. Diabetes was associated with higher risk of total invasive cancer (HR, 1.13; p < 0.001) and of several site-specific cancers (HR, 1.2–1.4, and up to over twofold). Diabetes was also associated with higher risk of death from cancer (HR, 1.46; p < 0.001). There was no overall difference in cancer incidence by diabetes therapy (p = 0.66). However, there was a lower risk of death from cancer for metformin users, compared to users of other medications, relative to women without diabetes, overall (HRs, 1.08 vs. 1.45; p = 0.007) and for breast cancer (HRs, 0.50 vs. 1.29; p = 0.05). Results also suggested that lower cancer risk associated with metformin may be evident only for a longer duration of use in certain cancer sites or subgroup populations. We provide further evidence that postmenopausal women with diabetes are at higher risk of invasive cancer and cancer death. Metformin users, particularly long-term users, may be at lower risk of developing certain cancers and dying from cancer, compared to users of other anti-diabetes medications. Future studies are needed to determine the long-term effect of metformin in cancer risk and survival from cancer. PMID:26616262

  6. Relationship between leukotriene-modifying agent prescriptions dispensed and rate of suicide deaths by county in the US

    Directory of Open Access Journals (Sweden)

    Schumock GT

    2011-09-01

    Full Text Available Glen T Schumock1, Robert D Gibbons2, Todd A Lee1,3,4,6, Min J Joo4, Robert J Valuck5, Leslie T Stayner61Center for Pharmacoeconomic Research, and Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA; 2Center for Health Statistics, and Departments of Medicine and Health Studies, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA; 3Center for Management of Complex Chronic Care, Hines VA Hospital, Hines, IL, USA; 4Section of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA; 5Department of Clinical Pharmacy, School of Pharmacy, University of Colorado, Aurora, CO, USA; 6Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, USABackground: The US Food and Drug Administration has issued warnings about a potential link between leukotriene receptor-modifying agents (LTMA and suicide. These warnings are based on case reports and there is controversy about the association. While spontaneous reporting of suicide-related events attributed to LTMA has risen dramatically, these data may be biased by the warnings. The objective of this study was to explore the relationship between LTMA and suicide deaths using event data preceding the Food and Drug Administration warnings.Methods: We conducted a mixed-effects Poisson regression analysis of the association between LTMA prescriptions dispensed and suicide deaths at the county level. Counts of suicide deaths in each US county, stratified by race, age group, gender, and year were obtained from the National Center for Health Statistics for the period January 1, 1999 to December 31, 2006. Counts of LTMA prescriptions dispensed in each US county were obtained from IMS Health Incorporated. The model estimated the overall suicide rate conditional on LTMA use, adjusted for age, gender, race, year

  7. Dose-Dependent ATP Depletion and Cancer Cell Death following Calcium Electroporation, Relative Effect of Calcium Concentration and Electric Field Strength

    OpenAIRE

    Hansen, Emilie Louise; Sozer, Esin Bengisu; Romeo, Stefania; Frandsen, Stine Krog; Vernier, P. Thomas; Gehl, Julie

    2015-01-01

    Background Electroporation, a method for increasing the permeability of membranes to ions and small molecules, is used in the clinic with chemotherapeutic drugs for cancer treatment (electrochemotherapy). Electroporation with calcium causes ATP (adenosine triphosphate) depletion and cancer cell death and could be a novel cancer treatment. This study aims at understanding the relationship between applied electric field, calcium concentration, ATP depletion and efficacy. Methods In three human ...

  8. Nimbolide Sensitizes Human Colon Cancer Cells to TRAIL through Reactive Oxygen Species- and ERK-dependent Up-regulation of Death Receptors, p53, and Bax*

    OpenAIRE

    Gupta, Subash C.; Reuter, Simone; Phromnoi, Kanokkarn; Park, Byoungduck; Hema, Padmanabhan S.; Nair, Mangalam; Aggarwal, Bharat B.

    2010-01-01

    TNF-related apoptosis-inducing ligand (TRAIL) shows promise as a cancer treatment, but acquired tumor resistance to TRAIL is a roadblock. Here we investigated whether nimbolide, a limonoid, could sensitize human colon cancer cells to TRAIL. As indicated by assays that measure esterase activity, sub-G1 fractions, mitochondrial activity, and activation of caspases, nimbolide potentiated the effect of TRAIL. This limonoid also enhanced expression of death receptors (DRs) DR5 and DR4 in cancer ce...

  9. AUTOPHAGY IN LUNG CANCER

    OpenAIRE

    Jaboin, Jerry J.; Hwang, Misun; Lu, Bo

    2009-01-01

    Lung cancer is the leading cause of cancer-related deaths worldwide. The relatively poor cure rate in lung cancer patients has been associated with a resistance to chemotherapy and radiation that is at least in part related to defects in cellular apoptotic machinery. Exploitation of another form of cell death, autophagy, has the capacity to improve the therapeutic gain of current therapies. In an effort to develop novel treatment strategies to enhance the therapeutic ratio for lung cancer, we...

  10. Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells.

    Science.gov (United States)

    Ogura, Takeharu; Tanaka, Yoshiyuki; Tamaki, Hiroki; Harada, Mamoru

    2016-06-01

    Docetaxel is a useful chemotherapeutic agent for the first-line treatment of hormone-refractory prostate cancer. Abnormal expression of Bcl-2 is commonly found in cancer cells, which increases their anti-apoptotic potency and chemoresistance. We investigated the effects of Bcl-2 expression status on the susceptibility of DU145 cells, an androgen-independent human prostate cancer cell line, to docetaxel and other anticancer agents. A panel of Bcl-2-expressing DU145 cell lines was established. Bcl-2 expression levels were unrelated to the susceptibility of DU145 cells to docetaxel. The sensitivity of DU145 cells to cisplatin fluctuated, and the sensitivity to tumor necrosis factor (TNF)-α was decreased by Bcl-2 overexpression. In a xenograft mouse model, overexpression of Bcl-2 drastically decreased the sensitivity of DU145 cells to cisplatin and TNF-α; however, there was no change in the response to docetaxel. Fluorescent microscopy revealed that Bcl-2-overexpression had no effect on the docetaxel-induced death of DU145 cells, but significantly decreased DU145 cell death induced by cisplatin or TNF-α. Interestingly, docetaxel hardly induced caspase-3/7 activation in control or Bcl-2-overexpressing DU145 cells, but did at a low level in LNCaP cells, another prostate cancer cell line. Moreover, in contrast to LNCaP cells, the reduced viabilities of docetaxel-treated control and Bcl-2-overexpressing DU145 cells were not restored by the addition of either a Bid inhibitor or a panel of pro-apoptotic caspase inhibitors. These findings indicate that the antitumor effects of docetaxel on DU145 cells are independent of both Bcl-2 and pro-apoptotic caspases. PMID:27082738

  11. Investigation of epothilone B-induced cell death mechanisms in human epithelial cancer cells -in consideration of combined treatment with ionizing radiation.

    Science.gov (United States)

    Baumgart, Tonja; Kriesen, Stephan; Neels, Oliver; Hildebrandt, Guido; Manda, Katrin

    2015-07-01

    Epothilone B was shown to have promising chemo- and radiosensitizing effects on cells, but the mechanisms underlying cell death remain ambiguous. The aim of the study was to examine selected cell death pathways on the basis of FaDu and A549 cells. Western blot analyses were used for investigation of specific apoptotic markers. Immunofluorescence imaging and flow cytometry were utilized for examination of cell death mechanisms. DNA-staining was used for studying influence of epothilone B on micronucleus rate. We showed that epothilone B can initiate cell death via apoptosis and mitotic catastrophe, but induction of cell death was cell type specific. PMID:25919223

  12. Urethral stricture following high dose rate brachytherapy for prostate cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma. Methods and materials: Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0. Results: At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n = 15) or optical urethrotomy (n = 20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p = 0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p = 0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p = 0.008). Conclusions: BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.

  13. Forced migration and mortality in the very long term: did perestroika affect death rates also in Finland?

    Science.gov (United States)

    Saarela, Jan; Finnäs, Fjalar

    2009-08-01

    In this article, we analyze mortality rates of Finns born in areas that were ceded to the Soviet Union after World War II and from which the entire population was evacuated. These internally displaced persons are observed during the period 1971-2004 and compared with people born in the same region but on the adjacent side of the new border. We find that in the 1970s and 1980s, the forced migrants had mortality rates that were on par with those of people in the comparison group. In the late 1980s, the mortality risk of internally displaced men increased by 20% in relation to the expected time trend. This deviation, which manifests particularly in cardiovascular mortality, coincides with perestroika and the demise of the Soviet Union, which were events that resulted in an intense debate in civil society about restitution of the ceded areas. Because state actors were reluctant to engage, the debate declined after some few years, and after the mid-1990s, the death risk again approached the long-term trend. Our findings indicate that when internally displaced persons must adjust to situations for which appropriate coping behaviors are unknown, psychosocial stress might arise several decades after their evacuation. PMID:19771945

  14. Annual Screening with Chest X-Ray Does Not Reduce Lung Cancer Deaths

    Science.gov (United States)

    Annual screening for lung cancer using a standard chest x-ray does not reduce the risk of dying from lung cancer when compared with no annual screening, according to findings from the NCI-led Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial.

  15. Selective cell death mediated by small conditional RNAs:a novel therapeutic approach to cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Che-Kai Tsao; William K Oh

    2011-01-01

    @@ Targeted molecular therapy has been an elusive goal in the treatment of neo-plastic diseases.While chemotherapy has improved the outcome of many cancers, a non-selective cytotoxic approach invariably causes damage to normal cells, resulting in side effects and limiting treatment efficacy.This is evident in the evolution of treatment for castration-resistant prostate cancer (CRPC).

  16. Fluid shear stress sensitizes cancer cells to receptor-mediated apoptosis via trimeric death receptors

    International Nuclear Information System (INIS)

    Cancer metastasis, the process of cancer cell migration from a primary to distal location, typically leads to a poor patient prognosis. Hematogenous metastasis is initiated by intravasation of circulating tumor cells (CTCs) into the bloodstream, which are then believed to adhere to the luminal surface of the endothelium and extravasate into distal locations. Apoptotic agents such as tumor necrosis factor apoptosis-inducing ligand (TRAIL), whether in soluble ligand form or expressed on the surface of natural killer cells, have shown promise in treating CTCs to reduce the probability of metastasis. The role of hemodynamic shear forces in altering the cancer cell response to apoptotic agents has not been previously investigated. Here, we report that human colon cancer COLO 205 and prostate cancer PC-3 cells exposed to a uniform fluid shear stress in a cone-and-plate viscometer become sensitized to TRAIL-induced apoptosis. Shear-induced sensitization directly correlates with the application of fluid shear stress, and TRAIL-induced apoptosis increases in a fluid shear stress force- and time-dependent manner. In contrast, TRAIL-induced necrosis is not affected by the application fluid shear stress. Interestingly, fluid shear stress does not sensitize cancer cells to apoptosis when treated with doxorubicin, which also induces apoptosis in cancer cells. Caspase inhibition experiments reveal that shear stress-induced sensitization to TRAIL occurs via caspase-dependent apoptosis. These results suggest that physiological fluid shear forces can modulate receptor-mediated apoptosis of cancer cells in the presence of apoptotic agents. (paper)

  17. Coronary artery calcification detected in lung cancer screening predicts cardiovascular death

    DEFF Research Database (Denmark)

    Rasmussen, Thomas; Køber, Lars; Abdulla, Jawdat;

    2015-01-01

    OBJECTIVES: It remains unknown whether non-electrocardiogram-gated coronary artery calcium (CAC) score in lung cancer screening provides incremental prognostic value. The aim of this study was to evaluate the prognostic value of CAC in the Danish Lung Cancer Screening Trial (DLCST), in addition t...

  18. Xylitol induces cell death in lung cancer A549 cells by autophagy.

    Science.gov (United States)

    Park, Eunjoo; Park, Mi Hee; Na, Hee Sam; Chung, Jin

    2015-05-01

    Xylitol is a widely used anti-caries agent that has anti-inflammatory effects. We have evaluated the potential of xylitol in cancer treatment. It's effects on cell proliferation and cytotoxicity were measured by MTT assay and LDH assay. Cell morphology and autophagy were examined by immunostaining and immunoblotting. Xylitol inhibited cell proliferation in a dose-dependent manner in these cancer cells: A549, Caki, NCI-H23, HCT-15, HL-60, K562, and SK MEL-2. The IC50 of xylitol in human gingival fibroblast cells was higher than in cancer cells, indicating that it is more specific for cancer cells. Moreover, xylitol induced autophagy in A549 cells that was inhibited by 3-methyladenine, an autophagy inhibitor. These results indicate that xylitol has potential in therapy against lung cancer by inhibiting cell proliferation and inducing autophagy of A549 cells. PMID:25650339

  19. Ectopic expression of Flt3 kinase inhibits proliferation and promotes cell death in different human cancer cell lines.

    Science.gov (United States)

    Oveland, Eystein; Wergeland, Line; Hovland, Randi; Lorens, James B; Gjertsen, Bjørn Tore; Fladmark, Kari E

    2012-08-01

    Stable ectopic expression of Flt3 receptor tyrosine kinase is usually performed in interleukin 3 (IL-3)-dependent murine cell lines like Ba/F3, resulting in loss of IL-3 dependence. Such high-level Flt3 expression has to date not been reported in human acute myeloid leukemia (AML) cell lines, despite the fact that oncogenic Flt3 aberrancies are frequent in AML patients. We show here that ectopic Flt3 expression in different human cancer cell lines might reduce proliferation and induce apoptotic cell death, involving Bax/Bcl2 modulation. Selective depletion of Flt3-expressing cells occurred in human AML cell lines transduced with retroviral Flt3 constructs, shown here using the HL-60 leukemic cell line. Flt3 expression was investigated in two cellular model systems, the SAOS-2 osteosarcoma cell line and the human embryonic kidney HEK293 cell line, and proliferation was reduced in both systems. HEK293 cells underwent apoptosis upon ectopic Flt3 expression and cell death could be rescued by overexpression of Bcl-2. Furthermore, we observed that the Flt3-induced inhibition of proliferation in HL-60 cells appeared to be Bax-dependent. Our results thus suggest that excessive Flt3 expression has growth-suppressive properties in several human cancer cell lines. PMID:22422053

  20. Docetaxel induced-JNK2/PHD1 signaling pathway increases degradation of HIF-1α and causes cancer cell death under hypoxia

    Science.gov (United States)

    Oh, Eun-Taex; Kim, Chan Woo; Kim, Soo Jung; Lee, Jae-Seon; Hong, Soon-Sun; Park, Heon Joo

    2016-01-01

    HIF-1 (hypoxia-inducible factor-1) regulates the expression of more than 70 genes involved in angiogenesis, tumor growth, metastasis, chemoresistance, and radioresistance. Thus, there is growing interest in using HIF-1 inhibitors as anticancer drugs. Docetaxel, a Food and Drug Administration-approved anticancer drug, is reported to enhance HIF-1α degradation. Here, we investigated the molecular mechanism underlying docetaxel-induced HIF-1α degradation and cancer cell death under hypoxic conditions. Docetaxel pretreatment enhanced the polyubiquitination and proteasome-mediated degradation of HIF-1α, and increased cancer cell death under hypoxic conditions. Docetaxel also activated the prolyl hydroxylase, PHD1, in hypoxia, and pharmacological inhibition or siRNA-mediated knockdown of PHD1 prevented docetaxel-induced HIF-1α degradation and cancer cell death. Additionally, siRNA-mediated JNK2 knockdown blocked docetaxel-induced HIF-1α degradation and cancer cell death by inhibiting PHD1 activation. A luciferase reporter assay revealed that inhibition of the JNK2/PHD1 signaling pathway significantly increased the transcriptional activity of HIF-1 in docetaxel-treated cancer cells under hypoxia. Consistent with these results, docetaxel-treated JNK2-knockdown tumors grew much faster than control tumors through inhibition of docetaxel-induced PHD1 activation and degradation of HIF-1α. Our results collectively show that, under hypoxic conditions, docetaxel induces apoptotic cell death through JNK2/PHD1 signaling-mediated HIF-1α degradation. PMID:27263528

  1. TRAIL and docosahexaenoic acid cooperate to induce HT-29 colon cancer cell death

    Czech Academy of Sciences Publication Activity Database

    Vaculová, Alena; Hofmanová, Jiřina; Anděra, Ladislav; Kozubík, Alois

    2005-01-01

    Roč. 229, č. 1 (2005), s. 43-48. ISSN 0304-3835 R&D Projects: GA ČR(CZ) GA524/04/0895; GA ČR(CZ) GA524/03/0766 Institutional research plan: CEZ:AV0Z50040507 Keywords : TRAIL * DHA * cell death Subject RIV: BO - Biophysics Impact factor: 3.049, year: 2005

  2. Measurement of OH, O, and NO densities and their correlations with mouse melanoma cell death rate treated by a nanosecond pulsed streamer discharge

    Science.gov (United States)

    Yagi, Ippei; Shirakawa, Yuki; Hirakata, Kenta; Akiyama, Taketoshi; Yonemori, Seiya; Mizuno, Kazue; Ono, Ryo; Oda, Tetsuji

    2015-10-01

    Mouse melanoma cells in a culture medium are treated using a nanosecond pulsed streamer discharge plasma and the correlations between the rate of cell death and the densities of reactive species (OH, O, and NO) in the plasma are measured. The plasma is irradiated onto the culture medium surface with a vertical gas flow of an O2/N2 mixture from a glass tube at various gas flow rates and O2 concentrations. The densities of the reactive species are measured very close to the culture medium surface, where the reactive species interact with the culture medium, using laser-induced fluorescence. In the case of the N2 discharge (O2 = 0%), an increase in gas flow rate decreases OH density because it lowers the water vapor concentration by diluting the vapor, which is required for OH production. The increase in gas flow rate also leads to a decreased cell death rate. In the case of the O2/N2 discharge, on the other hand, an increase in O2 concentration at a fixed flow rate does not affect the rate of cell death, although it considerably changes the O and NO densities. These findings indicate that some reactive species derived from water vapor such as OH are responsible for the melanoma cell death, whereas those from O2, such as O and NO, are less likely responsible. They also indicate the importance of water evaporation from the culture medium surface in cell treatment.

  3. Antisense bcl-2 treatment increases programmed cell death in non-small cell lung cancer cell lines.

    Science.gov (United States)

    Koty, P P; Zhang, H; Levitt, M L

    1999-02-01

    Programmed cell death (PCD) is a genetically regulated pathway that is altered in many cancers. This process is, in part, regulated by the ratio of PCD inducers (Bax) or inhibitors (Bcl-2). An abnormally high ratio of Bcl-2 to Bax prevents PCD, thus contributing to resistance to chemotherapeutic agents, many of which are capable of inducing PCD. Non-small cell lung cancer (NSCLC) cells demonstrate resistance to these PCD-inducing agents. If Bcl-2 prevents NSCLC cells from entering the PCD pathway, then reducing the amount of endogenous Bcl-2 product may allow these cells to spontaneously enter the PCD pathway. Our purpose was to determine the effects of bcl-2 antisense treatment on the levels of programmed cell death in NSCLC cells. First, we determined whether bcl-2 and bax mRNA were expressed in three morphologically distinct NSCLC cell lines: NCI-H226 (squamous), NCI-H358 (adenocarcinoma), and NCI-H596 (adenosquamous). Cells were then exposed to synthetic antisense bcl-2 oligonucleotide treatment, after which programmed cell death was determined, as evidenced by DNA fragmentation. Bcl-2 protein expression was detected immunohistochemically. All three NSCLC cell lines expressed both bcl-2 and bax mRNA and had functional PCD pathways. Synthetic antisense bcl-2 oligonucleotide treatment resulted in decreased Bcl-2 levels, reduced cell proliferation, decreased cell viability, and increased levels of spontaneous PCD. This represents the first evidence that decreasing Bcl-2 in three morphologically distinct NSCLC cell lines allows the cells to spontaneously enter a PCD pathway. It also indicates the potential therapeutic use of antisense bcl-2 in the treatment of NSCLC. PMID:10217615

  4. Cytotoxicity of obacunone and obacunone glucoside in human prostate cancer cells involves Akt-mediated programmed cell death

    International Nuclear Information System (INIS)

    Highlights: • Possible mechanism of inhibiting LNCaP cells proliferation by obacunone and obacunone glucoside is demonstrated for the first time. • Inhibition of LNCaP cells by limonoids though induction of programmed cell death, inhibition of cell signaling and inflammatory pathways. • Limonoids exhibited multi-mode inhibition of androgen expression in LNCaP cells. - Abstract: Obacunone and obacunone glucoside (OG) are naturally occurring triterpenoids commonly found in citrus and other plants of the Rutaceae family. The current study reports the mechanism of cytotoxicity of citrus-derived obacunone and OG on human androgen-dependent prostate cancer LNCaP cells. Both limonoids exhibited time- and dose-dependent inhibition of cell proliferation, with more than 60% inhibition of cell viability at 100 μM, after 24 and 48 h. Analysis of fragmentation of DNA, activity of caspase-3, and cytosolic cytochrome-c in the cells treated with limonoids provided evidence for activation of programmed cell death by limonoids. Treatment of LNCaP cells with obacunone and OG resulted in dose-dependent changes in expression of proteins responsible for the induction of programmed cell death through the intrinsic pathway and down-regulation of Akt, a key molecule in cell signaling pathways. In addition, obacunone and OG also negatively regulated an inflammation-associated transcription factor, androgen receptor, and prostate-specific antigen, and activated proteins related to the cell cycle, confirming the ability of limonoids to induce cytotoxicity through multiple pathways. The results of this study provided, for the first time, an evidence of the cytotoxicity of obacunone and OG in androgen-dependent human prostate cancer cells

  5. Roles of dCK Ser-74 in radiation-induced cell death in breast cancer cells

    International Nuclear Information System (INIS)

    Objective: To investigate the roles of dCK Ser-74 in radiation-induced cell death in breast cancer cells. Methods: Different phenotypes of dCK plasmids were transfected into MCF-7 cells by liposome transfection, including dCK-Vector, dCK-WT (wild type), dCK-S74A (non-phosphorylation) and dCK-S74E (hyper-phosphorylation). All these cells were irradiated by 0, 2, 4, 6, 8 Gy X-rays, respectively. The transcriptional and translational level of dCK were detected with real time-PCR and Western blot, respectively. Radiosensitivity was analyzed using cell counting kit (CCK-8) and colony formation assays. Monodansylcadaverine staining (MDC) and flow cytometry were used to detect autophagy and apoptosis,respectively. Results: Four phenotypes of dCK cell models were established successfully. After irradiation, the cell viabilities of MCF-7 and dCK-Vector decreased significantly as compared with mock group (t=14.469 and 9.357, P<0.05), the cell viabilities of dCK-WT, dCK-S74A and dCK-S74E showed no changes (P>0.05). The total mortalities of dCK-WT and dCK-S74E decreased significantly as compared with dCK-Vector (χ2=3.857-3.971, P<0.05), but no changes in dCK-S74A cells (P>0.05). The apoptosis rates in dCK-S74A, dCK-Vector and control group were up-regulated after irradiation (t=-4.531, -3.688 and-7.076, P<0.05), and the irradiation-induced apoptosis was reversed in dCK-WT and dCK-S74E (66% and 68% of the increase level in dCK-Vector group). The autophagy in dCK-WT and dCK-S74E increased by 22% and 26% (t=-9.051 and-8.411, P<0.01), but no changes were observed in dCK-S74A, dCK-Vector and control groups (P>0.05). Conclusions: The dCK-WT and dCK-S74E could reverse the irradiation-induced apoptosis, increase the autophagy occurrence, and decrease the total mortality, indicating that the phosphorylation of dCK at Ser-74 sites is related to the radiosensitivity of MCF-7 cells. (authors)

  6. Radical Decisions in Cancer: Redox Control of Cell Growth and Death

    Energy Technology Data Exchange (ETDEWEB)

    Sainz, Rosa M., E-mail: sainzrosa@uniovi.es [Cellular Biology and Morphology Department, School of Medicine, University of Oviedo, Oviedo 33006 (Spain); University Institute of Oncology of Asturias (IUOPA), University of Oviedo, Oviedo 33006 (Spain); Lombo, Felipe [University Institute of Oncology of Asturias (IUOPA), University of Oviedo, Oviedo 33006 (Spain); Functional Biology Department, Area of Microbiology, School of Medicine, University of Oviedo, Oviedo 33006 (Spain); Mayo, Juan C. [Cellular Biology and Morphology Department, School of Medicine, University of Oviedo, Oviedo 33006 (Spain); University Institute of Oncology of Asturias (IUOPA), University of Oviedo, Oviedo 33006 (Spain)

    2012-04-25

    Free radicals play a key role in many physiological decisions in cells. Since free radicals are toxic to cellular components, it is known that they cause DNA damage, contribute to DNA instability and mutation and thus favor carcinogenesis. However, nowadays it is assumed that free radicals play a further complex role in cancer. Low levels of free radicals and steady state levels of antioxidant enzymes are responsible for the fine tuning of redox status inside cells. A change in redox state is a way to modify the physiological status of the cell, in fact, a more reduced status is found in resting cells while a more oxidative status is associated with proliferative cells. The mechanisms by which redox status can change the proliferative activity of cancer cells are related to transcriptional and posttranscriptional modifications of proteins that play a critical role in cell cycle control. Since cancer cells show higher levels of free radicals compared with their normal counterparts, it is believed that the anti-oxidative stress mechanism is also increased in cancer cells. In fact, the levels of some of the most important antioxidant enzymes are elevated in advanced status of some types of tumors. Anti-cancer treatment is compromised by survival mechanisms in cancer cells and collateral damage in normal non-pathological tissues. Though some resistance mechanisms have been described, they do not yet explain why treatment of cancer fails in several tumors. Given that some antitumoral treatments are based on the generation of free radicals, we will discuss in this review the possible role of antioxidant enzymes in the survival mechanism in cancer cells and then, its participation in the failure of cancer treatments.

  7. Radical Decisions in Cancer: Redox Control of Cell Growth and Death

    International Nuclear Information System (INIS)

    Free radicals play a key role in many physiological decisions in cells. Since free radicals are toxic to cellular components, it is known that they cause DNA damage, contribute to DNA instability and mutation and thus favor carcinogenesis. However, nowadays it is assumed that free radicals play a further complex role in cancer. Low levels of free radicals and steady state levels of antioxidant enzymes are responsible for the fine tuning of redox status inside cells. A change in redox state is a way to modify the physiological status of the cell, in fact, a more reduced status is found in resting cells while a more oxidative status is associated with proliferative cells. The mechanisms by which redox status can change the proliferative activity of cancer cells are related to transcriptional and posttranscriptional modifications of proteins that play a critical role in cell cycle control. Since cancer cells show higher levels of free radicals compared with their normal counterparts, it is believed that the anti-oxidative stress mechanism is also increased in cancer cells. In fact, the levels of some of the most important antioxidant enzymes are elevated in advanced status of some types of tumors. Anti-cancer treatment is compromised by survival mechanisms in cancer cells and collateral damage in normal non-pathological tissues. Though some resistance mechanisms have been described, they do not yet explain why treatment of cancer fails in several tumors. Given that some antitumoral treatments are based on the generation of free radicals, we will discuss in this review the possible role of antioxidant enzymes in the survival mechanism in cancer cells and then, its participation in the failure of cancer treatments

  8. NAMPT inhibition synergizes with NQO1-targeting agents in inducing apoptotic cell death in non-small cell lung cancer cells.

    Science.gov (United States)

    Liu, Hui-Ying; Li, Qing-Ran; Cheng, Xue-Fang; Wang, Guang-Ji; Hao, Hai-Ping

    2016-08-01

    Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD(+), essential for a number of enzymes and regulatory proteins involved in a variety of cellular processes, including deacetylation enzyme SIRT1 which modulates several tumor suppressors such as p53 and FOXO. Herein we report that NQO1 substrates Tanshione IIA (TSA) and β-lapachone (β-lap) induced a rapid depletion of NAD(+) pool but adaptively a significant upregulation of NAMPT. NAMPT inhibition by FK866 at a nontoxic dose significantly enhanced NQO1-targeting agent-induced apoptotic cell death. Compared with TSA or β-lap treatment alone, co-treatment with FK866 induced a more dramatic depletion of NAD(+), repression of SIRT1 activity, and thereby the increased accumulation of acetylated FOXO1 and the activation of apoptotic pathway. In conclusion, the results from the present study support that NAMPT inhibition can synergize with NQO1 activation to induce apoptotic cell death, thereby providing a new rationale for the development of combinative therapeutic drugs in combating non-small lung cancer. PMID:27608947

  9. Cancer Rates by Race/Ethnicity and Sex

    Science.gov (United States)

    ... more information about this message, please visit this page: About CDC.gov . Cancer Home Kinds of Cancer Bladder Breast Cervical Colorectal (Colon) Kidney Liver Lung Ovarian Prostate Skin Uterine Vaginal and Vulvar How ...

  10. 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)

    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

  11. Lower heart rate variability is associated with cancer-related fatigue in breast cancer survivors

    Directory of Open Access Journals (Sweden)

    Alexandra Dupont

    2012-09-01

    Full Text Available Background : Fatigue is the most common and distressing symptom reported by breast cancer survivors and yet the pathophysiology of cancer-related fatigue remains largely unknown. Fatigue is associated with lower parasympathetic and higher sympathetic nervous system activity in non-cancer samples, but only one study has demonstrated this same relationship in breast cancer survivors. This study evaluates the relationship between fatigue and basal autonomic nervous system activity as measured by heart rate variability (HRV in a sample of breast cancer survivors. Methods : Women who had been diagnosed with early stage breast cancer before the age of 50 were recruited from the UCLA tumor registry and completed psychological questionnaires, including measures of fatigue. A subset of these women (n=30 participated in a follow-up study in which they completed measures of fatigue, energy and mood four times per day for 5 days using electronic diaries, provided 3 days of saliva samples for cortisol assessment and underwent physiological assessment including electrocardiogram (ECG. HRV was assessed via ECG R-R wave spectral and time sequence analysis. Results : Questionnaire measures of fatigue were negatively associated with indices of parasympathetic nervous system activity, B= − 3.85, p = 0.04 for RMSSD (root of the mean squared difference of successive normal to normal waves and B= − 76.97, p = 0.04 for LF power % (low-frequency wave power percentage. Daily fatigue was also associated with lower basal HRV, B= − 15.1, p = 0.04 for RMSSD. However, fatigue indices were not associated with sympathetic nervous system activity as measured by low- to high-frequency wave ratio. Of note, fatigue was not associated with average daily cortisol output (AUC. Conclusions : Lower HRV has been associated with increased chronic inflammation, which is elevated in cancer survivors reporting persistent fatigue, thus providing insight into

  12. High dose rate brachytherapy for prostate cancer. The first report

    Energy Technology Data Exchange (ETDEWEB)

    Kitano, Masashi; Nishiguchi, Iku; Isobe, Yoshinori; Irie, Akira; Egawa, Shin; Hayakawa, Kazushige [Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine

    2001-09-01

    Iridium-192 high-dose-rate (HDR) brachytherapy may improve local control because of more outstanding dose distribution than external beam radiotherapy in patients with prostate cancer. We report the experience of HDR-brachytherapy for prostate cancer. Between June 1999 and August 2000, forty-five patients with carcinoma of the prostate were treated by using HDR-brachytherapy followed by external beam radiotherapy at Kitasato University East Hospital. T1, 2, 3, T4 and unknown tumors were found in 14, 19, 10, 1 and 1 cases respectively. Using a perineal template, eighteen afterloading needles were inserted to the prostate and seminal vesicle. Then a CT scan was performed to ensure the relationship between needles and the prostate. Treatment volume was defined at 5 mm outside of the capsule of the prostate. Dose prescription was 4 Gy per fraction, and total dose was 20 Gy/5 fractions/3 days. External beam conformal irradiation was then given to the prostate and seminal vesicle to a dose of 30 Gy/10 fractions in two weeks. The median follow-up time was 6.6 months (range, 1.5-14.4 months). Treatment in all patients could be accomplished. No patient experienced acute side-effects of grade 3 or higher. One patient developed a late intestinal side-effect of grade 3. In our institution, because the tips of afterloading needles were inserted through the prostate into the lumen of the bladder, good dose distribution was obtained. It is suggested that this treatment was effective to decrease PSA value and can be safely performed even in old patients. (author)

  13. A NATURAL WAY TO CANCER PREVENTION AND THERAPY

    Directory of Open Access Journals (Sweden)

    Anupama Sharma

    2013-02-01

    Full Text Available In economically developing countries, the global burden of cancer persists to increase chiefly because of the aging and growth of the world population along with an increasing implementation of cancercausing behaviors, particularly smoking, physical inactivity and fast food. Cancer group accounts approximately 13% of all deaths each year with the most common being: lung cancer (1.3 million deaths, stomach cancer (803,000 deaths, colorectal cancer (639,000 deaths, liver cancer (610,000 deaths, and breast cancer (519,000 deaths. In India, the rate of oral, oesophagus and cervical cancers are some highest in the world according to 2011 Statistics. Various treatments are used to cure some cancers, but the battle against this disease is ongoing. The source of biologically active compounds originally isolated from plants. These natural compounds can acts as anti cancerous agents. Hence, the current study focuses on the use of 15 different natural products in the treatment of cancer.

  14. Assessment of risk for asthma initiation and cancer and heart disease deaths among patrons and servers due to secondhand smoke exposure in restaurants and bars

    OpenAIRE

    Liu, Ruiling; Bohac, David L; Gundel, Lara A.; Hewett, Martha J; Apte, Michael G; Hammond, S. Katharine

    2013-01-01

    Background Despite efforts to reduce exposure to secondhand smoke (SHS), only 5% of the world's population enjoy smoke-free restaurants and bars. Methods Lifetime excess risk (LER) of cancer death, ischaemic heart disease (IHD) death and asthma initiation among non-smoking restaurant and bar servers and patrons in Minnesota and the US were estimated using weighted field measurements of SHS constituents in Minnesota, existing data on tobacco use and multiple dose-response models. Results A con...

  15. Somatostatin receptor subtype 2 sensitizes human pancreatic cancer cells to death ligand-induced apoptosis.

    Science.gov (United States)

    Guillermet, Julie; Saint-Laurent, Nathalie; Rochaix, Philippe; Cuvillier, Olivier; Levade, Thierry; Schally, Andrew V; Pradayrol, Lucien; Buscail, Louis; Susini, Christiane; Bousquet, Corinne

    2003-01-01

    Somatostatin receptor subtype 2 (sst2) gene expression is lost in 90% of human pancreatic adenocarcinomas. We previously demonstrated that stable sst2 transfection of human pancreatic BxPC-3 cells, which do not endogenously express sst2, inhibits cell proliferation, tumorigenicity, and metastasis. These sst2 effects occur as a consequence of an autocrine sst2-dependent loop, whereby sst2 induces expression of its own ligand, somatostatin. Here we investigated whether sst2 induces apoptosis in sst2-transfected BxPC-3 cells. Expression of sst2 induced a 4.4- +/- 0.05-fold stimulation of apoptosis in BxPC-3 through the activation of tyrosine phosphatase SHP-1. sst2 also sensitized these cells to apoptosis induced by tumor necrosis factor alpha (TNFalpha), enhancing it 4.1- +/- 1.5-fold. Apoptosis in BxPC-3 cells mediated by TNF-related apoptosis-inducing ligand (TRAIL) and CD95L was likewise increased 2.3- +/- 0.5-fold and 7.4- +/- 2.5-fold, respectively. sst2-dependent activation and cell sensitization to death ligand-induced apoptosis involved activation of the executioner caspases, key factors in both death ligand- or mitochondria-mediated apoptosis. sst2 affected both pathways: first, by up-regulating expression of TRAIL and TNFalpha receptors, DR4 and TNFRI, respectively, and sensitizing the cells to death ligand-induced initiator capase-8 activation, and, second, by down-regulating expression of the antiapoptotic mitochondrial Bcl-2 protein. These results are of interest for the clinical management of chemoresistant pancreatic adenocarcinoma by using a combined gene therapy based on the cotransfer of genes for both the sst2 and a nontoxic death ligand. PMID:12490654

  16. Communicative practices in talking about death and dying in the context of Thai cancer care.

    Science.gov (United States)

    Wilainuch, Pairote

    2013-01-01

    This article explores communicative practices surrounding how nurses, patients and family members engage when talking about death and dying, based on study conducted in a province in northern Thailand. Data were collected from three environments: a district hospital (nine cases), district public health centres (four cases), and in patients' homes (27 cases). Fourteen nurses, 40 patients and 24 family members gave written consent for participation. Direct observation and in-depth interviews were used for supplementary data collection, and 40 counselling sessions were recorded on video. The raw data were analysed using Conversation Analysis. The study found that Thai counselling is asymmetrical. Nurses initiated the topic of death by referring to the death of a third person--a dead patient--with the use of clues and via list-construction. As most Thai people are oriented to Buddhism, religious support is selected for discussing this sensitive topic, and nurses also use Buddhism and list-construction to help their clients confront uncertain futures. However, Buddhism is not brought into discussion on its own, but combined with other techniques such as the use of euphemisms or concern and care for others. PMID:25233563

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

    KAUST Repository

    Martinez Banderas, Aldo

    2016-04-01

    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-release drug profiles, and increase the half-life of drugs. In this context, magnetic nanowires (NWs) have shown a good biocompatibility and cellular internalization with a low cytotoxic effect. In this thesis, I induced cancer cell death by combining the chemotherapeutic effect of iron NWs functionalized with Doxorubicin (DOX) with mechanical disturbance under a low frequency alternating magnetic field. Two different agents, APTES and BSA, were separately used for coating NWs permitting further functionalization with DOX. Internalization was qualitatively and quantitatively assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal reflection analysis, BSA formulations demonstrate to have a higher internalization degree and a broader distribution within the cells in comparison to APTES formulations. Both groups of functionalized NWs generated a comparable cytotoxic effect in MDA-MB-231 breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by the free DOX (~95% at the same concentration) and non-functionalized NWs formulations (~10% at the same NWs concentration). A synergistic cytotoxic effect is obtained when a low frequency magnetic field (1 mT, 10 Hz) is applied to cells treated with the two formulations that is again comparable (~70% at the highest concentration). Furthermore, the cytotoxic effect of both groups of coated NWs without the drug increased notoriously when the field is applied (~25% at the highest concentration tested). Here, a novel bimodal method for cancer cell destruction was developed by the conjugation of the magneto

  18. Elevated heart rate triggers action potential alternans and sudden death. translational study of a homozygous KCNH2 mutation.

    Directory of Open Access Journals (Sweden)

    Ulrich Schweigmann

    Full Text Available BACKGROUND: Long QT syndrome (LQTS leads to arrhythmic events and increased risk for sudden cardiac death (SCD. Homozygous KCNH2 mutations underlying LQTS-2 have previously been termed "human HERG knockout" and typically express severe phenotypes. We studied genotype-phenotype correlations of an LQTS type 2 mutation identified in the homozygous index patient from a consanguineous Turkish family after his brother died suddenly during febrile illness. METHODS AND RESULTS: Clinical work-up, DNA sequencing, mutagenesis, cell culture, patch-clamp, in silico mathematical modelling, protein biochemistry, confocal microscopy were performed. Genetic analysis revealed a homozygous C-terminal KCNH2 mutation (p.R835Q in the index patient (QTc ∼506 ms with notched T waves. Parents were I° cousins - both heterozygous for the mutation and clinically unremarkable (QTc ∼447 ms, father and ∼396 ms, mother. Heterologous expression of KCNH2-R835Q showed mildly reduced current amplitudes. Biophysical properties of ionic currents were also only nominally changed with slight acceleration of deactivation and more negative V50 in R835Q-currents. Protein biochemistry and confocal microscopy revealed similar expression patterns and trafficking of WT and R835Q, even at elevated temperature. In silico analysis demonstrated mildly prolonged ventricular action potential duration (APD compared to WT at a cycle length of 1000 ms. At a cycle length of 350 ms M-cell APD remained stable in WT, but displayed APD alternans in R835Q. CONCLUSION: Kv11.1 channels affected by the C-terminal R835Q mutation display mildly modified biophysical properties, but leads to M-cell APD alternans with elevated heart rate and could precipitate SCD under specific clinical circumstances associated with high heart rates.

  19. Programmed cell death ligand-1 (PD-L1) expression by immunohistochemistry: could it be predictive and/or prognostic in non-small cell lung cancer?

    Science.gov (United States)

    Mino-Kenudson, Mari

    2016-01-01

    Blockade of immune checkpoints has recently emerged as a novel therapeutic strategy in various tumors. In particular, monoclonal antibodies targeting programmed cell death 1 (PD-1) or its ligand (PD-L1) have been most studied in lung cancer, and PD-1 inhibitors are now established agents in the management of non-small cell lung cancer (NSCLC). The reports on high-profile clinical trials have shown the association of PD-L1 expression by immunohistochemistry (IHC) with higher overall response rates to the PD-1/PD-L1 axis blockade suggesting that PD-L1 expression may serve as a predictive marker. Unfortunately, however, each PD-1 or PD-L1 inhibitor is coupled with a specific PD-L1 antibody, IHC protocol and scoring system for the biomarker assessment, making the head-to-head comparison of the studies difficult. Similarly, multiple clinical series that correlated PD-L1 expression with clinicopathologic and/or molecular variables and/or survival have reported conflicting results. The discrepancy could be explained by the differences in ethnicity and/or histologic types included in the studies, but it appears to be attributed in part to the differences in PD-L1 IHC methods. Thus, orchestrated efforts to standardize the PD-L1 IHC are warranted to establish the IHC as a predictive and/or prognostic biomarker in NSCLC.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. IGF-I activates caspases 3/7, 8 and 9 but does not induce cell death in colorectal cancer cells

    International Nuclear Information System (INIS)

    Colorectal cancer is the third most common cancer in the western world. Chemotherapy is often ineffective to treat the advanced colorectal cancers due to the chemo-resistance. A major contributor to chemo-resistance is tumour-derived inhibition or avoidance of apoptosis. Insulin-like growth factor I (IGF-I) has been known to play a prominent role in colorectal cancer development and progression. The role of IGF-I in cancer cell apoptosis is not completely understood. Using three colorectal cancer cell lines and one muscle cell line, associations between IGF-I and activities of caspase 3/7, 8 and 9 have been examined; the role of insulin-like growth factor I receptor (IGF-IR) in the caspase activation has been investigated. The results show that exogenous IGF-I significantly increases activity of caspases 3/7, 8 and 9 in all cell lines used; blocking IGF-I receptor reduce IGF-I-induced caspase activation. Further studies demonstrate that IGF-I induced caspase activation does not result in cell death. This is the first report to show that while IGF-I activates caspases 3/7, 8 and 9 it does not cause colorectal cancer cell death. The study suggests that caspase activation is not synonymous with apoptosis and that activation of caspases may not necessarily induce cell death

  2. High dose rate vaginal brachytherapy in endometrial cancer after surgery

    International Nuclear Information System (INIS)

    Purpose. - This study aimed at analyzing the evolution and type of recurrence in patients treated for stage I endometrial carcinomas, in order to define the respective roles of adjuvant radiotherapy and brachytherapy. Patients and methods. - This mono-centric retrospective study was conducted at Centre Alexis-Vautrin, Nancy, France, between January 1995 and December 2000 on all the patients surgically treated for an endometrial cancer, and then treated with high dose rate vaginal brachytherapy. The brachytherapy was delivered in two or three fractions of 7 Gy at 5 mm from the applicator. Results. - In the good prognosis group, the specific and overall survivals at 5 years were respectively 96.5 and 94.2% with no local recurrence demonstrated. In the intermediate prognostic group, the specific and overall survivals at 5 years were respectively 88 and 85%, with six locoregional recurrences observed among those who did not undergo lymphadenectomy; the overall survival at 5 years was significantly decreased in the absence of external radiation. In the group of poor prognosis (stages II and III), the specific survival at 5 years was respectively 72.8 and 67 %, and the overall survival at 5 years 66.7 and 56.4%. Conclusion. - Results for local control and survival as well as for tolerance were good. So we have decided to deliver high rate brachytherapy for all intermediate or poor prognosis patients and we have abandoned pelvic radiotherapy for good prognosis tumours (stages IA: no myometrium invasion with grade 3 and >50% of myometrium invasion with grades 1 and 2), whatever the lymph nodes surgery they had. We now propose pelvic radiotherapy only for intermediate prognosis tumours (such as IA > 50% of myometrium invasion with grade 3 and IB stages), if patients did not have any lymphatic surgery, or for bad prognosis tumours. (authors)

  3. 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)

    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

  4. 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.

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

    International Nuclear Information System (INIS)

    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

  6. Comparison of Rates of Death Having any Death-Certificate Mention of Heart, Kidney, or Liver Disease Among Persons Diagnosed with HIV Infection with those in the General US Population, 2009-2011

    OpenAIRE

    Whiteside, Y. Omar; Selik, Richard; An, Qian; Huang, Taoying; Karch, Debra; Hernandez, Angela L; Hall, H. Irene

    2015-01-01

    Objective : Compare age-adjusted rates of death due to liver, kidney, and heart diseases during 2009-2011 among US residents diagnosed with HIV infection with those in the general population. Methods : Numerators were numbers of records of multiple-cause mortality data from the national vital statistics system with an ICD-10 code for the disease of interest (any mention, not necessarily the underlying cause), divided into those 1) with and 2) without an additional code for HIV infection. Deno...

  7. 沈阳市1998~2008年肺癌死亡状况及趋势分析%ANALYSIS OF THE DEATH SITUATION AND TREND OF LUNG CANCER IN SHENYANG FROM 1998 TO 2006

    Institute of Scientific and Technical Information of China (English)

    吕艺

    2011-01-01

    [目的] 了解沈阳市1998~2008年肺癌死亡状况,为开展肺癌的一级预防提供科学依据.[方法] 将沈阳市各医院从1998~2008年所上报到沈阳市CDC经临床、CT以及病理检测确诊并已经死亡的肺癌病例通过三间分布进行研究.[结果] 沈阳市肺癌死亡占恶性肿瘤死亡的36.94%;肺癌租死亡率为64.62/10万,男性肺癌死亡率较女性上升显著,各年龄组男性肺癌死亡率均高于女性(P<0.05).[结论] 沈阳市肺癌是恶性肿瘤的第1位死因;肺癌死亡率高于全国平均水平,男女肺癌死亡率均排全国前例;肺癌死亡年龄构成有了新的变化.沈阳市五城区人口构成不同及肺癌危险因素的变化,造成各区肺癌死亡率的差异%[Objective] To understand the death situation of lung cancer in Shenyang from 1998 to 2006, so as provide basis for carrying out the first prevention of lung cancer. [ Methods ] The information of data of lung cancer cases was diagnosed by clinic, chest X-ray, CT and pathology examination from 1998 to 2008. We performed description analysis for the data of lung cancer. [ Results] The mortality of lung cancer accounted for 36.94% of the malignancy. The Crude death rate of lung cancer was 646.2/105. Compared with that of females, the mortality of lung cancer of males significantly increased, and the lung cancer mortalities of males of various ages were significantly higher. [ Conclusion] The lung cancer is chief reason of death of malignancy in Shenyang. The mortality of lung cancer in the city zone of Shenyang ia higher than the average level in China, and the mortality of lung cancer of both males and females ranks in the front in China. The age at death of the new lung cancer patients are changing and beconunS younger. The risk factors of lung cancer in the five district areas is changing, which induced the tendency variations of death of lung cancer.

  8. Variability in Immunohistochemical Detection of Programmed Death Ligand 1 (PD-L1 in Cancer Tissue Types

    Directory of Open Access Journals (Sweden)

    Giosuè Scognamiglio

    2016-05-01

    Full Text Available In normal cell physiology, programmed death 1 (PD-1 and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues.

  9. Variability in Immunohistochemical Detection of Programmed Death Ligand 1 (PD-L1) in Cancer Tissue Types

    Science.gov (United States)

    Scognamiglio, Giosuè; De Chiara, Anna; Di Bonito, Maurizio; Tatangelo, Fabiana; Losito, Nunzia Simona; Anniciello, Annamaria; De Cecio, Rossella; D’Alterio, Crescenzo; Scala, Stefania; Cantile, Monica; Botti, Gerardo

    2016-01-01

    In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues. PMID:27213372

  10. Variability in Immunohistochemical Detection of Programmed Death Ligand 1 (PD-L1) in Cancer Tissue Types.

    Science.gov (United States)

    Scognamiglio, Giosuè; De Chiara, Anna; Di Bonito, Maurizio; Tatangelo, Fabiana; Losito, Nunzia Simona; Anniciello, Annamaria; De Cecio, Rossella; D'Alterio, Crescenzo; Scala, Stefania; Cantile, Monica; Botti, Gerardo

    2016-01-01

    In normal cell physiology, programmed death 1 (PD-1) and its ligand, PD-L1, play an immunoregulatory role in T-cell activation, tolerance, and immune-mediated tissue damage. The PD-1/PD-L1 pathway also plays a critical role in immune escape of tumor cells and has been demonstrated to correlate with a poor prognosis of patients with several types of cancer. However, recent reports have revealed that the immunohistochemical (IHC) expression of the PD-L1 in tumor cells is not uniform for the use of different antibodies clones, with variable specificity, often doubtful topographical localization, and with a score not uniquely defined. The purpose of this study was to analyze the IHC expression of PD-L1 on a large series of several human tumors to correctly define its staining in different tumor tissues. PMID:27213372

  11. The association of culling and death rate within 30 days after calving with productivity or reproductive performance in dairy herds in Fukuoka, Southern Japan.

    Science.gov (United States)

    Goto, Akira; Nakada, Ken; Katamoto, Hiromu

    2016-05-01

    The incidence of peripartum disorders in dairy herds negatively influences productivity and reproductive performance. Concrete data from local areas are helpful for explaining the importance of peripartum management to dairy farmers. This study was conducted to clarify the association of culling and death rate within 30 days after calving with productivity or reproductive performance in 179 dairy herds in Fukuoka, Southern Japan. A database was compiled from the records of the Livestock Improvement Association of Japan, the Dairy Cooperative Association and the Federation of Agricultural Mutual Relief Association. In this study, we created a comprehensive database of dairy farm production data for epidemiological analysis and used a general linear mixed model to analyze the association of culling and death rate within 30 days after calving with milk production or reproductive performance. The database can be used to describe, analyze and predict the risk of production. A cross-sectional analysis with contrasts was applied to investigate the association of cows served by AI/all cows, pregnant cows/cows served by AI, days open, milk yield and somatic cell counts with culling and death rate within 30 days after calving. The days open value significantly increased with increasing rate of culling and death within 30 days after calving (P for trend postpartum reproductive performance in this dairy cow cohort. PMID:26666177

  12. Investigation of selective induction of breast cancer cells to death with treatment of plasma-activated medium

    Science.gov (United States)

    Hashizume, Hiroshi; Tanaka, Hiromasa; Nakamura, Kae; Kano, Hiroyuki; Ishikawa, Kenji; Kikkawa, Fumitaka; Mizuno, Masaaki; Hori, Masaru

    2015-09-01

    The applications of plasma in medicine have much attention. We previously showed that plasma-activated medium (PAM) induced glioblastoma cells to apoptosis. However, it has not been elucidated the selectivity of PAM in detail. In this study, we investigated the selective effect of PAM on the death of human breast normal and cancer cells, MCF10A and MCF7, respectively, and observed the selective death with fluorescent microscopy. For the investigation of cell viability with PAM treatment, we prepared various PAMs according to the strengths, and treated each of cells with PAMs. Week PAM treatment only decreased the viability of MCF7 cells, while strong PAM treatment significantly affected both viabilities of MCF7 and MCF10A cells. For the fluorescent observation, we prepared the mixture of MCF7 and fluorescent-probed MCF10A cells, and seeded them. After the treatment of PAMs, the images showed that only MCF7 cells damaged in the mixture with week PAM treatment. These results suggested that a specific range existed with the selective effect in the strength of PAM. This work was partly supported by a Grant-in-Aid for Scientific Research on Innovative Areas ``Plasma Medical Innovation'' Grant No. 24108002 and 24108008 from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

  13. 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. PMID:27575372

  14. Suppression of the death gene BIK is a critical factor for resistance to tamoxifen in MCF-7 breast cancer cells.

    Science.gov (United States)

    Viedma-Rodriguez, Rubí; Baiza-Gutman, Luis Arturo; García-Carrancá, Alejandro; Moreno-Fierros, Leticia; Salamanca-Gómez, Fabio; Arenas-Aranda, Diego

    2013-12-01

    Apoptosis is controlled by the BCL-2 family of proteins, which can be divided into three different subclasses based on the conservation of BCL-2 homology domains. BIK is a founding member of the BH3-only pro-apoptotic protein family. BIK is predominantly localized in the endoplasmic reticulum (ER) and induces apoptosis through the mitochondrial pathway by mobilizing calcium from the ER to the mitochondria. In this study, we determined that suppression of the death gene Bik promotes resistance to tamoxifen (TAM) in MCF-7 breast cancer cells. We utilized small interfering (siRNA) to specifically knockdown BIK in MCF-7 cells and studied their response to tamoxifen. The levels of cell apoptosis, the potential mitochondrial membrane (∆Ψ(m)), and the activation of total caspases were analyzed. Western blot analysis was used to determine the expression of some BCL-2 family proteins. Flow cytometry studies revealed an increase in apoptosis level in MCF-7 cells and a 2-fold increase in relative BIK messenger RNA (mRNA) expression at a concentration of 6.0 μM of TAM. BIK silencing, with a specific RNAi, blocked TAM-induced apoptosis in 45 ± 6.78% of cells. Moreover, it decreased mitochondrial membrane potential (Ψm) and total caspase activity, and exhibited low expression of pro-apoptotic proteins BAX, BAK, PUMA and a high expression of BCl-2 and MCL-1. The above suggests resistance to TAM, regulating the intrinsic pathway and indicate that BIK comprises an important factor in the process of apoptosis, which may exert an influence the ER pathway, which regulates mitochondrial integrity. Collectively, our results show that BIK is a central component of the programmed cell death of TAM-induced MCF-7 breast cancer cells. The silencing of BIK gene will be useful for future studies to establish the mechanisms of regulation of resistance to TAM. PMID:24100375

  15. Comparing primary prevention with secondary prevention to explain decreasing coronary heart disease death rates in Ireland, 1985-2000.

    LENUS (Irish Health Repository)

    Kabir, Zubair

    2007-01-01

    BACKGROUND: To investigate whether primary prevention might be more favourable than secondary prevention (risk factor reduction in patients with coronary heart disease(CHD)). METHODS: The cell-based IMPACT CHD mortality model was used to integrate data for Ireland describing CHD patient numbers, uptake of specific treatments, trends in major cardiovascular risk factors, and the mortality benefits of these specific risk factor changes in CHD patients and in healthy people without recognised CHD. RESULTS: Between 1985 and 2000, approximately 2,530 fewer deaths were attributable to reductions in the three major risk factors in Ireland. Overall smoking prevalence declined by 14% between 1985 and 2000, resulting in about 685 fewer deaths (minimum estimate 330, maximum estimate 1,285) attributable to smoking cessation: about 275 in healthy people and 410 in known CHD patients. Population total cholesterol concentrations fell by 4.6%, resulting in approximately 1,300 (minimum estimate 1,115, maximum estimate 1,660) fewer deaths attributable to dietary changes(1,185 in healthy people and 115 in CHD patients) plus 305 fewer deaths attributable to statin treatment (45 in people without CHD and 260 in CHD patients). Mean population diastolic blood pressure fell by 7.2%, resulting in approximately 170 (minimum estimate 105, maximum estimate 300) fewer deaths attributable to secular falls in blood pressure (140 in healthy people and 30 in CHD patients), plus approximately 70 fewer deaths attributable to antihypertensive treatments in people without CHD. Of all the deaths attributable to risk factor falls, some 1,715 (68%) occurred in people without recognized CHD and 815(32%) in CHD patients. CONCLUSION: Compared with secondary prevention, primary prevention achieved a two-fold larger reduction in CHD deaths. Future national CHD policies should therefore prioritize nationwide interventions to promote healthy diets and reduce smoking.

  16. ANALYSIS OF RELAPSE RATE AND METASTASES OF HIGH DIFFERENTIATED THYROID CANCER

    Directory of Open Access Journals (Sweden)

    E. V. Savenok

    2015-01-01

    Full Text Available  Analysis of rate of relapses and metastases with well-differentiated thyroid cancer was performed for patients in 2009 to 2013. The study involved 189 patients with thyroid cancer including 98 (51.9 % patients suffering from papillary thyroid cancer, 77 (40.7 % patients suffering from follicular thyroid cancer, and 14 (7.4 % patients suffering from medullary thyroid cancer. 2.04 % of the 98 patients suffering from papillary thyroid cancer manifested a relapse, and lymphogenic metastases of cancer were revealed with 1.0 % of patients. With follicular thyroid cancer (n = 77, lymphogenic metastases were registered in 7.8 % of cases, relapses were revealed in 1.3 % of cases. This analysis demonstrated that observation of patients for 5 years revealed a higher percentage of metastases with patients that suffered from follicular thyroid cancer.

  17. Incidence rate of lung cancer in urban Shijiazhuang in 2012 with prevention implication

    OpenAIRE

    Wen, Denggui; Li, Shumei; Zhang, Min; Zhang, Nan; Wen, Xiaoduo; Yi YANG; Fen, Cheng; WANG, SHIJIE; Shan, Baoen

    2015-01-01

    Abstract Background Pollution has been established as an environmental factor in the development of lung cancer; however, the incidence rate in Shijiazhuang, one of China's most heavily polluted cities, is unknown. Methods As Chinese citizens are entitled to complete public medical insurance coverage, we estimated the lung cancer incidence rate among registered citizens of urban Shijiazhuang in 2012 using reimbursement records of first hospitalization. Results In Shijiazhuang, lung cancer was...

  18. High Israeli mortality rates from diabetes and renal failure - Can international comparison of multiple causes of death reflect differences in choice of underlying cause?

    OpenAIRE

    Goldberger, Nehama; Applbaum, Yael; Meron, Jill; Haklai, Ziona

    2015-01-01

    Background The age-adjusted mortality rate in Israel is low compared to most Western countries although mortality rates from diabetes and renal failure in Israel are amongst the highest, while those from cardiovascular diseases (CVD) are amongst the lowest. This study aims to assess validity of choice of underlying causes (UC) in Israel by analyzing Israeli and international data on the prevalence of these diseases as multiple causes of death (MCOD) compared to UC, and data on comorbidity (MC...

  19. Post-operative breast cancer patients diagnosed with skeletal metastasis without bone pain had fewer skeletal-related events and deaths than those with bone pain

    Directory of Open Access Journals (Sweden)

    Koizumi Mitsuru

    2010-08-01

    Full Text Available Abstract Background Skeletal metastases are often accompanied by bone pain. To investigate the clinical meaning of bone pain associated with skeletal metastasis in breast cancer patients after surgery, we explored whether the presence of bone pain was due to skeletal-related events (SREs or survival (cause specific death, CSD, retrospectively. Methods Consecutive breast cancer patients undergoing surgery between 1988 and 1998 were examined for signs of skeletal metastasis until December 2006. Patients who were diagnosed as having skeletal metastasis were the subjects of this study. Bone scans were performed annually for 5, 7 or 10 years; they were also conducted if skeletal metastasis was suspected. Data concerning bone pain and tumor markers at the time of skeletal metastasis diagnosis, and data relating to various factors including tumors, lymph nodes and hormone receptors at the time of surgery, were investigated. The relationships between factors such as bone pain, SRE and CSD were analyzed using the Kaplan-Meier method and Cox's analysis. Results Skeletal metastasis occurred in 668 patients but the pain status of two patients was unknown, therefore 666 patients were included in the study. At the time of skeletal metastasis diagnosis 270 patients complained of pain; however, 396 patients did not. Analysis of data using Cox's and Kaplan-Meier methods demonstrated that patients without pain had fewer SREs and better survival rates than those with pain. Hazard ratios regarding SRE (base = patients without pain were 2.331 in univariate analysis and 2.243 in multivariate analysis. Hazard ratios regarding CSD (base = patients without pain were 1.441 in univariate analysis and 1.535 in multivariate analysis. Similar results were obtained when analyses were carried out using the date of surgery as the starting point. Conclusion Bone pain at diagnosis of skeletal metastasis was an indicator of increased SRE and CSD. However, these data did not

  20. Redox-Active Selenium Compounds—From Toxicity and Cell Death to Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Sougat Misra

    2015-05-01

    Full Text Available Selenium is generally known as an antioxidant due to its presence in selenoproteins as selenocysteine, but it is also toxic. The toxic effects of selenium are, however, strictly concentration and chemical species dependent. One class of selenium compounds is a potent inhibitor of cell growth with remarkable tumor specificity. These redox active compounds are pro-oxidative and highly cytotoxic to tumor cells and are promising candidates to be used in chemotherapy against cancer. Herein we elaborate upon the major forms of dietary selenium compounds, their metabolic pathways, and their antioxidant and pro-oxidant potentials with emphasis on cytotoxic mechanisms. Relative cytotoxicity of inorganic selenite and organic selenocystine compounds to different cancer cells are presented as evidence to our perspective. Furthermore, new novel classes of selenium compounds specifically designed to target tumor cells are presented and the potential of selenium in modern oncology is extensively discussed.

  1. Tualang Honey Promotes Apoptotic Cell Death Induced by Tamoxifen in Breast Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Nik Soriani Yaacob

    2013-01-01

    Full Text Available Tualang honey (TH is rich in flavonoids and phenolic acids and has significant anticancer activity against breast cancer cells comparable to the effect of tamoxifen (TAM, in vitro. The current study evaluated the effects of TH when used in combination with TAM on MCF-7 and MDA-MB-231 cells. We observed that TH promoted the anticancer activity of TAM in both the estrogen receptor-(ER-responsive and ER-nonresponsive human breast cancer cell lines. Flow cytometric analyses indicated accelerated apoptosis especially in MDA-MB-231 cells and with the involvement of caspase-3/7, -8 and -9 activation as shown by fluorescence microscopy. Depolarization of the mitochondrial membrane was also increased in both cell lines when TH was used in combination with TAM compared to TAM treatment alone. TH may therefore be a potential adjuvant to be used with TAM for reducing the dose of TAM, hence, reducing TAM-induced adverse effects.

  2. Amicoumacin A induces cancer cell death by targeting the eukaryotic ribosome

    Science.gov (United States)

    Prokhorova, Irina V.; Akulich, Kseniya A.; Makeeva, Desislava S.; Osterman, Ilya A.; Skvortsov, Dmitry A.; Sergiev, Petr V.; Dontsova, Olga A.; Yusupova, Gulnara; Yusupov, Marat M.; Dmitriev, Sergey E.

    2016-01-01

    Amicoumacin A is an antibiotic that was recently shown to target bacterial ribosomes. It affects translocation and provides an additional contact interface between the ribosomal RNA and mRNA. The binding site of amicoumacin A is formed by universally conserved nucleotides of rRNA. In this work, we showed that amicoumacin A inhibits translation in yeast and mammalian systems by affecting translation elongation. We determined the structure of the amicoumacin A complex with yeast ribosomes at a resolution of 3.1  Å. Toxicity measurement demonstrated that human cancer cell lines are more susceptible to the inhibition by this compound as compared to non-cancerous ones. This might be used as a starting point to develop amicoumacin A derivatives with clinical value. PMID:27296282

  3. Piperlongumine promotes autophagy via inhibition of Akt/mTOR signalling and mediates cancer cell death

    OpenAIRE

    Makhov, P; Golovine, K.; Teper, E.; Kutikov, A.; Mehrazin, R.; Corcoran, A; A. Tulin; Uzzo, R G; Kolenko, V M

    2014-01-01

    Background: The Akt/mammalian target of rapamycin (mTOR) signalling pathway serves as a critical regulator of cellular growth, proliferation and survival. Akt aberrant activation has been implicated in carcinogenesis and anticancer therapy resistance. Piperlongumine (PL), a natural alkaloid present in the fruit of the Long pepper, is known to exhibit notable anticancer effects. Here we investigate the impact of PL on Akt/mTOR signalling. Methods: We examined Akt/mTOR signalling in cancer cell...

  4. Energy metabolism targeted drugs synergize with photodynamic therapy to potentiate breast cancer cell death.

    Science.gov (United States)

    Feng, Xiaolan; Zhang, Yi; Wang, Pan; Liu, Quanhong; Wang, Xiaobing

    2014-12-01

    Malignant cells are highly dependent on aerobic glycolysis, which differs significantly from normal cells (the Warburg effect). Interference of this metabolic process has been considered as an innovative method for developing selective cancer therapy. A recent study demonstrated that the glycolysis inhibitor 2-deoxyglucose (2-DG) can potentiate PDT efficacy, whereas the possible mechanisms have not been carefully investigated. This study firstly proved the general potentiation of PDT efficacy by 2-DG and 3-bromopyruvate (3-BP) in human breast cancer MDA-MB-231 cells, and carefully elucidated the underlying mechanism in the process. Our results showed that both 2-DG and 3-BP could significantly promote a PDT-induced cell cytotoxic effect when compared with either monotherapy. Synergistic potentiation of mitochondria- and caspase-dependent cell apoptosis was observed, including a mitochondrial membrane potential (MMP) drop, Bax translocation, and caspase-3 activation. Besides, ROS generation and the expression of oxidative stress related proteins such as P38 MAPK phosphorylation and JNK phosphorylation were notably increased after the combined treatments. Moreover, when pretreated with the ROS scavenger N-acetylcysteine (NAC), the ROS generation, the MMP drop, cell apoptosis and cytotoxicity were differently inhibited, suggesting that ROS was vertical in the pro-apoptotic process induced by 2-DG/3-BP combined with PDT treatment. These results indicate that the combination of glycolytic antagonists and PDT may be a promising therapeutic strategy to effectively kill cancer cells. PMID:25363473

  5. Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties

    Science.gov (United States)

    Samie, Nima; Muniandy, Sekaran; Kanthimathi, M. S.; Haerian, Batoul Sadat; Raja Azudin, Raja Elina

    2016-01-01

    The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC50 value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml respectively, after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-ƙB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines. PMID:27072064

  6. Colorectal cancer and diet in Scotland

    OpenAIRE

    Theodoratou, Evropi

    2008-01-01

    Introduction Colorectal cancer is a cancer that forms in the tissues of the colon and/ or rectum and more than 95% of colorectal cancers are adenocarcinomas. It is the third most common cancer in incidence and mortality rates, accounting for 9% of all cancer cases and for 8% of all cancer related deaths (2002). The established risk factors of colorectal cancer include personal or family history of previous colorectal cancer or adenomatous polyps, chronic bowel inflammatory d...

  7. Growth rate and characteristics of breast cancers detected by ultrasonography screening

    International Nuclear Information System (INIS)

    Breast cancer screening was carried out at our institution in a ''Human Dock'' style health check, by inspection and palpation, together with ultrasonography. Breast cancers detected were reviewed and the utility of ultrasonography was evaluated. A total of 14,063 women underwent the screening and the results were good, with a recall rate of 3.4%, a cancer detection rate of 0.30%, and a positive predictive value of 8.7%. Of 42 breast cancers detected by ultrasonography, 30 (71%) were 1.5 cm or less in diameter. For breast cancers detected by inspection and palpation, the detection rate for small cancers measuring 1.5 cm or less was 33% (10 out of 30 women), and 100% (12 women) for tumors measuring more than 1.5 cm. The cancer detection rate by mammography was 39% (9 out of 23 cancers) for tumors measuring 1.5 cm or less, and 91% (10 out of 11 cases) for those larger than 1.5 cm. Thus cancer detection by ultrasonography was optimal for tumors measuring 1.5 cm or less. Histologically proven lymph node metastasis was positive in 8 (25%) of 32 patients, among whom some had primary cancers measuring 1.5 cm or less. Tumor volume doubling time (TVDT) was measurable in 10 women; there was no change in size in one instance, and in the others TVDT was 4.8 to 32.5 months (mean 15.5 months), small cancers approximately 1 cm in size having a long TVDT. In women whose cancer size could be determined twice or more, TVDT tended to be short when a cancer measured about 1 cm or more. Cancers with a long TVDT showed low histological malignancy, and thus detection of breast cancers with a long TVDT at screening appears to be rewarding. (author)

  8. Dose-dependent ATP depletion and cancer cell death following calcium electroporation, relative effect of calcium concentration and electric field strength

    DEFF Research Database (Denmark)

    Hansen, Emilie Louise; Sozer, Esin Bengisu; Romeo, Stefania;

    2015-01-01

    BACKGROUND: Electroporation, a method for increasing the permeability of membranes to ions and small molecules, is used in the clinic with chemotherapeutic drugs for cancer treatment (electrochemotherapy). Electroporation with calcium causes ATP (adenosine triphosphate) depletion and cancer cell......-dependently reduced cell survival and intracellular ATP. Increasing extracellular calcium allows the use of a lower electric field. GENERAL SIGNIFICANCE: This study supports the use of calcium electroporation for treatment of cancer and possibly lowering the applied electric field in future trials....... death and could be a novel cancer treatment. This study aims at understanding the relationship between applied electric field, calcium concentration, ATP depletion and efficacy. METHODS: In three human cell lines--H69 (small-cell lung cancer), SW780 (bladder cancer), and U937 (leukaemia), viability was...

  9. Do female cancer patients display better survival rates compared with males? Analysis of the Korean National Registry data, 2005-2009.

    Directory of Open Access Journals (Sweden)

    Kyu-Won Jung

    Full Text Available BACKGROUND: Sex differences have been reported in the prognosis of certain cancers. In this study, we investigated whether Korean females display better survival rates compared with male patients for solid tumor sites. METHODS: We analyzed data from the Korean National Cancer Incidence Database from 599,288 adult patients diagnosed with solid cancers between 2005 and 2009. Patients were followed until December 2010. We applied a relative excess risk (RER model adjusting for year of follow-up, age at diagnosis, and stage at diagnosis. RESULTS: For all solid cancer sites combined, women displayed an 11% lower risk of death compared to men (RER 0.89; 95% CI 0.88-0.90 after adjusting for year of follow-up, age, stage, and case mix. Women showed significantly lower RERs for the following sites: head/neck, esophagus, small intestine, liver, nasal cavities, lung, bone/cartilages, melanoma of skin, soft tissue, brain and CNS, and thyroid. In contrast, women displayed a poorer prognosis than did men for colorectal, laryngeal, kidney and bladder cancer. However, the survival gaps between men and women narrowed by increase in age; female patients over 75 years of age displayed a 3% higher RER of death compared with males in this age group. CONCLUSIONS: Female cancer patients display an improved survival for the majority of solid tumor sites, even after adjustment for age and stage. Age at diagnosis was the major contributor to the women's survival advantage.

  10. CD4 count and viral load specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

    Directory of Open Access Journals (Sweden)

    A Mocroft

    2012-11-01

    Full Text Available Background CD4 and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or negatively affect the risk of disease this would not be identified prior to licensing. The aims of this study were to investigate the CD4 and viral load specific rates of fatal and non-fatal AIDS and non-AIDS events according to current antiretrovirals. Methods Poisson regression was used to compare overall events (fatal or non-fatal AIDS, non-AIDS or death, AIDS events (fatal and non-fatal or non-AIDS events (fatal or non-fatal for specific nucleoside pairs and third drugs used with>1000 person-years of follow-up (PYFU after January 1st 2001. Results 9801 patients were included. The median baseline date was January 2004 (interquartile range [IQR] January 2001–February 2007, age was 40.4 (IQR 34.6–47.3 years, and time since starting cART was 3.3 (IQR 0.9–5.1 years. At baseline, the median nadir CD4 was 162 (IQR 71–257/mm3, baseline CD4 was 390 (IQR 249–571/mm3, viral load was 1.9 (IQR 1.7–3.3 log10copies/ml and 2961 (30.2% had a prior AIDS diagnosis and 6.4 years prior to baseline. During 42372.5 PYFU, 1203 (437 AIDS and 766 non-AIDS events occurred. The overall event rate was 2.8 per 100 PYFU (95% confidence interval [CI] 2.7–3.0, of AIDS events was 1.0 (95% CI 0.9–1.1 and of non-AIDS events was 1.8 (95% CI 1.7–1.9. Of the AIDS events, 53 (12.1%were fatal as were 239 (31.2% of the non-AIDS events. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global p-value=0.084, and third drugs (global p-value=0.031. Compared to zidovudine/lamivudine, patients taking abacavir/lamivudine (adjusted incidence rate ratio [aIRR] 1.22; 95% CI 0.99–1.49 and abacavir plus one other nucleoside (aIRR 1.51; 95% CI 1.14–2.02 had an increased incidence of overall events. Comparing the third drugs

  11. The Growing Complexity of Cancer Cell Response to DNA-Damaging Agents: Caspase 3 Mediates Cell Death or Survival?

    Science.gov (United States)

    Mirzayans, Razmik; Andrais, Bonnie; Kumar, Piyush; Murray, David

    2016-01-01

    It is widely stated that wild-type p53 either mediates the activation of cell cycle checkpoints to facilitate DNA repair and promote cell survival, or orchestrates apoptotic cell death following exposure to cancer therapeutic agents. This reigning paradigm has been challenged by numerous discoveries with different human cell types, including solid tumor-derived cell lines. Thus, activation of the p53 signaling pathway by ionizing radiation and other DNA-damaging agents hinders apoptosis and triggers growth arrest (e.g., through premature senescence) in some genetic backgrounds; such growth arrested cells remain viable, secrete growth-promoting factors, and give rise to progeny with stem cell-like properties. In addition, caspase 3, which is best known for its role in the execution phase of apoptosis, has been recently reported to facilitate (rather than suppress) DNA damage-induced genomic instability and carcinogenesis. This observation is consistent with an earlier report demonstrating that caspase 3 mediates secretion of the pro-survival factor prostaglandin E2, which in turn promotes enrichment of tumor repopulating cells. In this article, we review these and related discoveries and point out novel cancer therapeutic strategies. One of our objectives is to demonstrate the growing complexity of the DNA damage response beyond the conventional “repair and survive, or die” hypothesis. PMID:27187358

  12. Parthenolide enhances sensitivity of colorectal cancer cells to TRAIL by inducing death receptor 5 and promotes TRAIL-induced apoptosis.

    Science.gov (United States)

    Kim, Se-Lim; Liu, Yu-Chuan; Park, Young Ran; Seo, Seung Young; Kim, Seong Hun; Kim, In Hee; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae-Ghon; Kim, Sang-Wook

    2015-03-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent. Recombinant human TRAIL has been evaluated in clinical trials, however, various malignant tumors are resistant to TRAIL. Parthenolide (PT) has recently been demonstrated as a highly effective anticancer agent and has been suggested to be used for combination therapy with other anticancer agents. In this study, we investigate the molecular mechanisms by which PT sensitizes colorectal cancer (CRC) cells to TRAIL-induced apoptosis. HT-29 (TRAIL-resistant) and HCT116 (TRAIL-sensitive) cells were treated with PT and/or TRAIL. The results demonstrated that combined treatment induced apoptosis which was determined using MTT, cell cycle analysis, Annexin V assay and Hoechst 33258 staining. Interestingly, we confirmed that HCT116 cells have much higher death receptor (DR) 5 than HT-29 cells and PT upregulates DR5 protein level and surface expression in both cell lines. Apoptosis through the mitochondrial pathway was confirmed by detecting regulation of Bcl-2 family members, p53 cytochrome C release, and caspase cascades. These results suggest that PT sensitizes TRAIL-induced apoptosis via upregulation of DR5 and mitochondria-dependent pathway. Combination treatment using PT and TRAIL may offer an effective strategy to overcome TRAIL resistance of certain CRC cells. PMID:25502339

  13. PET-CT detection rate of primary breast cancer lesions. Correlation with the clinicopathological factors

    International Nuclear Information System (INIS)

    One hundred and forty lesions of primary breast cancer underwent positron emission tomography (PET)-CT between June 2006 and May 2007. The PET-CT detection rate of primary breast cancer lesions was 72.1%. The detection rate was 52.1% for invasive cancer ≤20 mm, 92.8% for invasive breast cancers >20 mm, and these results were significant. In the present study, no significant relationship was observed between tumor types, however, invasive lobular carcinoma showed a lower detection rate, 58.3%. The PET-CT results were not significantly affected by either estrogen and progesterone receptors or distant metastasis. A significant correlation regarding the detection rate of PET-CT was found with HER2 status, tumor grade, and axillary lymph node status. The detection rate was 100% for invasive cancer ≤20 mm when the interval between prior diagnostic Mammotome biopsies and PET-CT was less than 3 weeks, 18.8% for invasive cancer ≤20 mm when the interval was more than 3 weeks, and these results were significant. Mammotome biopsies may therefore affect the detection rate of PET-CT. Invasive cancers ≤20 mm showed a low detection rate, therefore, it is considered to be insufficient to use PET-CT for the detection of early breast cancer. (author)

  14. Relationship of detection rate of PET cancer screening examinees and risk factors. Analysis of background of examinees

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) cancer screening is performed widely in Japan as opportunistic screening, but no study has focused on the correlation with various cancer risk factors and the seeking bias of examinees and cancer detection rate. Analyzing our large series of PET cancer screening data, correlations with cancer detection rates according to general cancer risk factors and PET detection survey were reviewed, and the selection bias of the medical examinees was determined. 19189 examinees who underwent PET cancer screening were enrolled. Using logistic-regression analysis, we analyzed correlations between smoking history/drinking history/cancer family history and detection rates of thyroid cancer/breast cancer/colorectal cancer/lung cancer, which are the main malignancies detected in PET cancer screening. In addition, we evaluated seeking bias of examinees, analyzing correlations between the presence of cancer risk factors and prior screening checkups at other institutions to our PET cancer screening using a matched case-control study. Cancer detection rates by FDG-PET were 1.17% (224/19189), being much higher than those of standard cancer mass screenings. In males, statistically significant correlations were seen between lung cancer and smoking, and between prostate cancer and a family history of prostate cancer, but not between the detection rates of three other types of cancer (thyroid cancer/lung cancer/colorectal cancer) and other cancer risk factors. In females, detection rates of four types of cancer (thyroid cancer/lung cancer/colorectal cancer/breast cancer) were significantly higher in the examinees without cancer risks, and subgroup analysis according to types of cancer did not indicate significant correlations either. The matched case-control study evaluating seeking bias indicated that a significant proportion of the examinees with cancer risks had undergone prior cancer screening at other institutions. Our study indicated that there was

  15. miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature present in Ta bladder tumors

    DEFF Research Database (Denmark)

    Ostenfeld, Marie Stampe; Bramsen, Jesper Bertram; Lamy, Philippe;

    2010-01-01

    Downregulation of miR-145 in a variety of cancers suggests a possible tumor suppressor function for this microRNA. Here, we show that miR-145 expression is reduced in bladder cancer and urothelial carcinoma in situ, compared with normal urothelium, using transcription profiling and in situ...... hybridization. Ectopic expression of miR-145 induced extensive apoptosis in urothelial carcinoma cell lines (T24 and SW780) as characterized by caspase activation, nuclear condensation and fragmentation, cellular shrinkage, and detachment. However, cell death also proceeded upon caspase inhibition by the...... pharmacological inhibitor zVAD-fmk and ectopic expression of anti-apoptotic Bcl-2, indicating the activation of an alternative caspase-independent death pathway. Microarray analysis of transcript levels in T24 cells, before the onset of cell death, showed destabilization of mRNAs enriched for miR-145 7mer target...

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

    International Nuclear Information System (INIS)

    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

  17. On the edge of death: Rates of decline and lower thresholds of biochemical condition in food-deprived fish larvae and juveniles

    Science.gov (United States)

    Meyer, S.; Caldarone, E. M.; Chícharo, M. A.; Clemmesen, C.; Faria, A. M.; Faulk, C.; Folkvord, A.; Holt, G. J.; Høie, H.; Kanstinger, P.; Malzahn, A.; Moran, D.; Petereit, C.; Støttrup, J. G.; Peck, M. A.

    2012-05-01

    Gaining reliable estimates of how long fish early life stages can survive without feeding and how starvation rate and time until death are influenced by body size, temperature and species is critical to understanding processes controlling mortality in the sea. The present study is an across-species analysis of starvation-induced changes in biochemical condition in early life stages of nine marine and freshwater fishes. Data were compiled on changes in body size (dry weight, DW) and biochemical condition (standardized RNA-DNA ratio, sRD) throughout the course of starvation of yolk-sac and feeding larvae and juveniles in the laboratory. In all cases, the mean biochemical condition of groups decreased exponentially with starvation time, regardless of initial condition and endogenous yolk reserves. A starvation rate for individuals was estimated from discrete 75th percentiles of sampled populations versus time (degree-days, Dd). The 10th percentile of sRD successfully approximated the lowest, life-stage-specific biochemical condition (the edge of death). Temperature could explain 59% of the variability in time to death whereas DW had no effect. Species and life-stage-specific differences in starvation parameters suggest selective adaptation to food deprivation. Previously published, interspecific functions predicting the relationship between growth rate and sRD in feeding fish larvae do not apply to individuals experiencing prolonged food deprivation. Starvation rate, edge of death, and time to death are viable proxies for the physiological processes under food deprivation of individual fish pre-recruits in the laboratory and provide useful metrics for research on the role of starvation in the sea.

  18. Gamma-secretase inhibition combined with platinum compounds enhances cell death in a large subset of colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Feller Stephan M

    2008-10-01

    Full Text Available Abstract Background Notch signalling is essential for the development and maintenance of the colonic epithelium. Its inhibition induces a differentiation phenotype in vivo and reduces adenomas in APCmin mice. Whether Notch signals are also required in colorectal cancer (CRC has remained elusive. Therefore, 64 CRC cell lines were analysed for the occurrence of proteolytically processed, active Notch. Results 63 CRC lines contained a fragment with approximately the size of the Notch1 intracellular domain (NICD, which is required for signalling. Subsequent analyses with an antibody that specifically recognises the free Val1744 residue generated by γ-secretase-mediated cleavage of Notch1 showed that a subset of CRC cells lacks this specific Val1744-NICD. Surprisingly, inhibition of Val1744-NICD signalling with different γ-secretase inhibitors (GSI did not lead to substantial effects on CRC cell line growth or survival. However, transient activation of Erk upon GSI treatment was detected. Since cisplatin relies on Erk activation for bioactivity in some cells, platinum compounds were tested together with GSI and enhanced cell killing in a subset of Val1744-NICD-positive CRC cell lines was detected. Erk inhibition ablated this combination effect. Conclusion We conclude that γ-secretase inhibition results in activation of the MAP kinases Erk1/2 and, when used in conjunction, enhances cell death induced by platinum compounds in a large subset of colorectal cancer cell lines. Furthermore the activation of Erk appears to be of particular importance in mediating the enhanced effect seen, as its inhibition abrogates the observed phenomenon. These findings do not only highlight the importance of signalling pathway crosstalk but they may also suggest a new avenue of combination therapy for some colorectal cancers.

  19. Combined treatment with cotylenin A and phenethyl isothiocyanate induces strong antitumor activity mainly through the induction of ferroptotic cell death in human pancreatic cancer cells.

    Science.gov (United States)

    Kasukabe, Takashi; Honma, Yoshio; Okabe-Kado, Junko; Higuchi, Yusuke; Kato, Nobuo; Kumakura, Shunichi

    2016-08-01

    The treatment of pancreatic cancer, one of the most aggressive gastrointestinal tract malignancies, with current chemotherapeutic drugs has had limited success due to its chemoresistance and poor prognosis. Therefore, the development of new drugs or effective combination therapies is urgently needed. Cotylenin A (CN-A) (a plant growth regulator) is a potent inducer of differentiation in myeloid leukemia cells and exhibits potent antitumor activities in several cancer cell lines. In the present study, we demonstrated that CN-A and phenethyl isothiocyanate (PEITC), an inducer of reactive oxygen species (ROS) and a dietary anticarcinogenic compound, synergistically inhibited the proliferation of MIAPaCa-2, PANC-1 and gemcitabine-resistant PANC-1 cells. A combined treatment with CN-A and PEITC also effectively inhibited the anchorage-independent growth of these cancer cells. The combined treatment with CN-A and PEITC strongly induced cell death within 1 day at concentrations at which CN-A or PEITC alone did not affect cell viability. A combined treatment with synthetic CN-A derivatives (ISIR-005 and ISIR-042) or fusicoccin J (CN-A-related natural product) and PEITC did not have synergistic effects on cell death. The combined treatment with CN-A and PEITC synergistically induced the generation of ROS. Antioxidants (N-acetylcysteine and trolox), ferroptosis inhibitors (ferrostatin-1 and liproxstatin), and the lysosomal iron chelator deferoxamine canceled the synergistic cell death. Apoptosis inhibitors (Z-VAD-FMK and Q-VD-OPH) and the necrosis inhibitor necrostatin-1s did not inhibit synergistic cell death. Autophagy inhibitors (3-metyladenine and chloroquine) partially prevented cell death. These results show that synergistic cell death induced by the combined treatment with CN-A and PEITC is mainly due to the induction of ferroptosis. Therefore, the combination of CN-A and PEITC has potential as a novel therapeutic strategy against pancreatic cancer. PMID:27375275

  20. Annual Report to the Nation on the Status of Cancer, 1975-2010: Questions and Answers

    Science.gov (United States)

    ... pharynx, and larynx) and increased for four others (cancer of the pancreas, liver, melanoma, and soft tissue including heart) (see ... cavity and pharynx, and gallbladder) and increased for cancers of the pancreas, liver, and uterus. 9. If cancer death rates ...

  1. Delayed luminescence to monitor programmed cell death induced by berberine on thyroid cancer cells

    Science.gov (United States)

    Scordino, Agata; Campisi, Agata; Grasso, Rosaria; Bonfanti, Roberta; Gulino, Marisa; Iauk, Liliana; Parenti, Rosalba; Musumeci, Francesco

    2014-11-01

    Correlation between apoptosis and UVA-induced ultraweak photon emission delayed luminescence (DL) from tumor thyroid cell lines was investigated. In particular, the effects of berberine, an alkaloid that has been reported to have anticancer activities, on two cancer cell lines were studied. The FTC-133 and 8305C cell lines, as representative of follicular and anaplastic thyroid human cancer, respectively, were chosen. The results show that berberine is able to arrest cell cycle and activate apoptotic pathway as shown in both cell lines by deoxyribonucleic acid fragmentation, caspase-3 cleavage, p53 and p27 protein overexpression. In parallel, changes in DL spectral components after berberine treatment support the hypothesis that DL from human cells originates mainly from mitochondria, since berberine acts especially at the mitochondrial level. The decrease of DL blue component for both cell lines could be related to the decrease of intra-mitochondrial nicotinamide adenine dinucleotide and may be a hallmark of induced apoptosis. In contrast, the response in the red spectral range is different for the two cell lines and may be ascribed to a different iron homeostasis.

  2. 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)

    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)

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

    Science.gov (United States)

    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.

  4. Toward a better understanding of the comparatively high prostate cancer incidence rates in Utah

    OpenAIRE

    Wiggins Charles L; Hilton Sterling C; Merrill Ray M; Sturgeon Jared D

    2003-01-01

    Abstract Background This study assesses whether comparatively high prostate cancer incidence rates among white men in Utah represent higher rates among members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormons), who comprise about 70% of the state's male population, and considers the potential influence screening has on these rates. Methods Analyses are based on 14,693 histologically confirmed invasive prostate cancer cases among men aged 50 years and older identified through...

  5. Impact of the 1998 Football World Cup on Suicide Rates in France: Results from the National Death Registry

    Science.gov (United States)

    Encrenaz, Gaelle; Contrand, Benjamin; Leffondre, Karen; Queinec, Raphaelle; Aouba, Albertine; Jougla, Eric; Miras, Alain; Lagarde, Emmanuel

    2012-01-01

    Our objective was to determine whether the Federation Internationale de Football Association (FIFA) World Cup in 1998 had a short-term impact on the number of suicides in France. Exhaustive individual daily data on suicides from 1979 to 2006 were obtained from the French epidemiological center on the medical causes of death (CepiDC-INSERM;…

  6. CDC WONDER: Mortality - Infant Deaths

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mortality - Infant Deaths (from Linked Birth / Infant Death Records) online databases on CDC WONDER provide counts and rates for deaths of children under 1 year...

  7. Time to second prostate specific antigen (PSA) failure is a surrogate endpoint for prostate cancer death in prospective trials of therapy for localized disease

    International Nuclear Information System (INIS)

    Purpose In assessing the efficacy of the competing curative therapies for prostate cancer the most relevant endpoint is cancer specific death. Due to the long natural history of the disease and the use of salvage androgen suppression prospective trials need to mature for at least a decade to provide meaningful results. An endpoint that predicted for cancer death with high probability would allow more rapid completion of prospective studies, hopefully before the tested therapies become outdated. Materials and methods 202 patients entered into a single institution prospective randomized study for T3-4 prostate cancer between 1982 and 1992 were evaluated. All received radical irradiation to either a standard dose of 67.2Gy or a higher dose of 75.6Gy (the latter employing a proton beam boost). 76 men have received androgen suppression or orchiectomy for salvage following relapse (median follow-up 6.9 years). Of this group 35 experienced a second relapse heralded by a rise in the serum PSA. Second failure was scored on the date that the serum PSA rose to greater than 10% above the post-androgen suppression nadir. Kaplan-Meier analysis was made of survival from the time of second PSA failure and the cause of death established in all patients who subsequently died. Results The median duration of response to hormone therapy following first failure was 27.2 months. The actuarial survival from the time of second biochemical relapse was 93%, 66%, 35%, and 0% at 1, 2, 3, and 4 years respectively (50% at 32 months). 16 patients have so far died after second failure all from causes related to their prostate cancer. Conclusion Second PSA failure appears to be a secure surrogate for impending prostate cancer death. Its use as an endpoint in prospective studies should allow earlier reporting by 2 - 3 years

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

    Directory of Open Access Journals (Sweden)

    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

  9. Neonatal Death

    Science.gov (United States)

    ... Home > Complications & Loss > Loss & grief > Neonatal death Neonatal death E-mail to a friend Please fill in ... your baby. What are common causes of neonatal death? The most common causes of neonatal death are: ...

  10. Colon cancer

    Science.gov (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma ... In the United States, colorectal cancer is one of the leading causes of deaths due to cancer. Early diagnosis can often lead to a complete cure. Almost ...

  11. STI571 reduces TRAIL-induced apoptosis in colon cancer cells: c-Abl activation by the death receptor leads to stress kinase-dependent cell death

    Directory of Open Access Journals (Sweden)

    Huang Duen-Yi

    2012-03-01

    Full Text Available Abstract Background In an effort to achieve better cancer therapies, we elucidated the combination cancer therapy of STI571 (an inhibitor of Bcr-Abl and clinically used for chronic myelogenous leukemia and TNF-related apoptosis-inducing ligand (TRAIL, a developing antitumor agent in leukemia, colon, and prostate cancer cells. Methods Colon cancer (HCT116, SW480, prostate cancer (PC3, LNCaP and leukemia (K562 cells were treated with STI571 and TRAIL. Cell viability was determined by MTT assay and sub-G1 appearance. Protein expression and kinase phosphorylation were determined by Western blotting. c-Abl and p73 activities were inhibited by target-specific small interfering (siRNA. In vitro kinase assay of c-Abl was conducted using CRK as a substrate. Results We found that STI571 exerts opposite effects on the antitumor activity of TRAIL. It enhanced cytotoxicity in TRAIL-treated K562 leukemia cells and reduced TRAIL-induced apoptosis in HCT116 and SW480 colon cancer cells, while having no effect on PC3 and LNCaP cells. In colon and prostate cancer cells, TRAIL caused c-Abl cleavage to the active form via a caspase pathway. Interestingly, JNK and p38 MAPK inhibitors effectively blocked TRAIL-induced toxicity in the colon, but not in prostate cancer cells. Next, we found that STI571 could attenuate TRAIL-induced c-Abl, JNK and p38 activation in HCT116 cells. In addition, siRNA targeting knockdown of c-Abl and p73 also reduced TRAIL-induced cytotoxicity, rendering HCT116 cells less responsive to stress kinase activation, and masking the cytoprotective effect of STI571. Conclusions All together we demonstrate a novel mediator role of p73 in activating the stress kinases p38 and JNK in the classical apoptotic pathway of TRAIL. TRAIL via caspase-dependent action can sequentially activate c-Abl, p73, and stress kinases, which contribute to apoptosis in colon cancer cells. Through the inhibition of c-Abl-mediated apoptotic p73 signaling, STI571 reduces

  12. A Social Marketing Approach To Increasing Breast Cancer Screening Rates.

    Science.gov (United States)

    Bryant, Carol A.; Forthofer, Melinda S.; McCormack Brown, Kelli; Alfonso, Moya Lynn; Quinn, Gwen

    2000-01-01

    Used social marketing to identify factors influencing women's breast cancer screening behaviors. Data from focus groups and interviews with diverse women highlighted women's attitudes, knowledge, and barriers regarding screening. Results were used to develop a comprehensive social marketing plan to motivate irregular users of breast cancer…

  13. High mortality rates after non-elective colon cancer resection

    DEFF Research Database (Denmark)

    Bakker, I S; Snijders, H S; Grossmann, Irene;

    2016-01-01

    obtained from the Dutch Surgical Colorectal Audit. Patients undergoing colon cancer resection in the Netherlands between January 2009 and December 2013 were included. Patient, treatment and tumour factors were analyzed in relation to the urgency of surgery. The primary outcome was the thirty day...

  14. Co-cultivation of cells as a promising tool in cancer research in vitro.

    NARCIS (Netherlands)

    Jongen, W.M.F.

    1988-01-01

    Epidemiological data show that in western societies I out of 3 persons gets cancer and I out of 4 persons dies of cancer. This makes cancer, next to heart and vascular diseases, a major cause of death. There are three major factors contributing to the cancer death rate in humans:1. ionizing radiatio

  15. Breast cancer incidence and survival: registry-based studies of long-term trends and determinants

    NARCIS (Netherlands)

    M.W.J. Louwman (Marieke)

    2007-01-01

    markdownabstract__Abstract__ Breast cancer is the most frequent cancer among women in the Netherlands, and it is the most important cause of cancer death. Between age 35 and 55 about 20% of all deaths among women is due to breast cancer.1 The age-standardised incidence rate is among the highest in

  16. Treatment-Related Death during Concurrent Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Meta-Analysis of Randomized Studies

    Science.gov (United States)

    Zhao, Jing; Xia, Yingfeng; Kaminski, Joseph; Hao, Zhonglin; Mott, Frank; Campbell, Jeff; Sadek, Ramses; Kong, Feng-Ming (Spring)

    2016-01-01

    Treatment related death (TRD) is the worst adverse event in chemotherapy and radiotherapy for patients with cancer, the reports for TRDs were sporadically. We aimed to study TRDs in non-small cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT), and determine whether high radiation dose and newer chemotherapy regimens were associated with the risk of TRD. Data from randomized clinical trials for locally advanced/unresectable NSCLC patients were analyzed. Eligible studies had to have at least one arm with CCRT. The primary endpoint was TRD. Pooled odds ratios (ORs) for TRDs were calculated. In this study, a total of fifty-three trials (8940 patients) were eligible. The pooled TRD rate (accounting for heterogeneity) was 1.44% for all patients. In 20 trials in which comparison of TRDs between CCRT and non-CCRT was possible, the OR (95% CI) of TRDs was 1.08 (0.70–1.66) (P = 0.71). Patients treated with third-generation chemotherapy and concurrent radiotherapy had an increase of TRDs compared to those with other regimens in CCRT (2.70% vs. 1.37%, OR = 1.50, 95% CI: 1.09–2.07, P = 0.008). No significant difference was found in TRDs between high (≥ 66 Gy) and low (< 66 Gy) radiation dose during CCRT (P = 0.605). Neither consolidation (P = 0.476) nor induction chemotherapy (P = 0.175) had significant effects with increased TRDs in this study. We concluded that CCRT is not significantly associated with the risk of TRD compared to non-CCRT. The third-generation chemotherapy regimens may be a risk factor with higher TRDs in CCRT, while high dose radiation is not significantly associated with more TRDs. This observation deserves further study. PMID:27300551

  17. Fulvic acid promotes extracellular anti-cancer mediators from RAW 264.7 cells, causing to cancer cell death in vitro.

    Science.gov (United States)

    Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Dilshara, Matharage Gayani; Kang, Chang-Hee; Lee, Seungheon; Choi, Yung Hyun; Jeong, Yong Kee; Kim, Gi-Young

    2016-07-01

    Fulvic acid (FA) is known to promote electrochemical balance as a donor or a receptor possessing many biomedical functions. Nevertheless, the effect of FA on the anti-cancer activity has not been elucidated. In the current study, we first isolated FA from humus and investigated whether FA regulates immune-stimulating functions, such as production of nitric oxide (NO), in RAW 264.7 cells. Our data showed that FA slightly enhances cell viability in a dose-dependent manner and secretion of NO from RAW 264.7 cells. It upregulated the protein and mRNA expression of inducible NO synthesis (iNOS). In addition, FA enhanced the DNA-binding activity of nuclear factor-κB (NF-κB) in RAW 264.7 cells; the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) effectively attenuated the expression of FA-stimulated iNOS, suggesting that FA stimulates NF-κB to promote iNOS and NO production. Finally, FA-stimulated culture media (FA-CM) from RAW 264.7 cells were collected and MCA-102 fibrosarcoma cells were cultured in this media. The FA-CM augmented MCA-102 fibrosarcoma cell apoptosis; however, an NO inhibitor N(G)-monomethyl-l-arginine (NMMA) slightly inhibited the FA-CM-mediated MCA-102 fibrosarcoma cell apoptosis, which was accompanied by low levels of NO. In the present study, we found that FA induces the generation of NO and iNOS in RAW 264.7 cells by inducing NF-κB activation; however, NO did not significantly stimulate MCA-102 fibrosarcoma cell apoptosis in the current study. In addition, FA-CM enhanced cell death in various human cancer cells such as Hep3B, LNCaP, and HL60. Taken together, FA most likely stimulates immune-modulating molecules such as NO and induces cancer cell apoptosis. PMID:27177083

  18. Analysis of the similarity factors of the villages in the areas of the nuclear power plants from the premature death-rate performed by fuzzy logic method

    International Nuclear Information System (INIS)

    Our paper examines the surrounding areas of NPP from the proportion of premature death-rate which is one of the complex indicators of the health situation of the population. Specially, attention is focused on NPP in Bohunice (SE-EBO) which has been in operation for the last 30 years and NPP Mochovce (SE-EMO) which was still under construction when data was collected. WHO considers every death of the individual before 65 years of age a premature death case, except death cases of children younger that 1 year. Because of the diversity of the population, this factor is a standard for the population of Slovak Republic (SR) as well as for the european population. The objective of the work is to prove, that even a long term production of energy in NPP does not evoke health problems for the population living in the surrounding areas, which could be recorded through analysis of premature death cases. Using the fuzzy logic method when searching for similar objects and evaluating the influence of the NPP on its surrounding area seems more natural than classical accumulation method, which separates objects into groups. When using the classical accumulation method, the objects in particular accumulation group are more similar than 2 objects in different accumulation groups. When using the fuzzy logic method the similarity is defined more naturally. Within the observed regions of the NPP, the percentage of directly standardized premature death cases is almost identical with the average for the SR. The most closely observed region of SE-EMO up to 5 kilometers zone even shows the lowest percentage. Also we did not record any areas that would have unfavourable values from the wind streams perspective neither than from the local water streams recipients of SE-EBO Manivier and Dudvah. The region of SE-EMO is also within the SR average, unfavourable coherent areas of premature death case are non existent. Galanta city region comes out of the comparison with the relatively worse

  19. Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance

    Directory of Open Access Journals (Sweden)

    Anna E. Maciag

    2013-01-01

    Full Text Available JS-K is a nitric oxide (NO-releasing prodrug of the O2-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models both in vitro and in vivo. The current study of the metabolic actions of JS-K was undertaken to investigate mechanisms of its cytotoxicity. Consistent with model chemical reactions, the activating step in the metabolism of JS-K in the cell is the dearylation of the diazeniumdiolate by glutathione (GSH via a nucleophilic aromatic substitution reaction. The resulting product (CEP/NO anion spontaneously hydrolyzes, releasing two equivalents of NO. The GSH/GSSG redox couple is considered to be the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. We have quantified the effects of JS-K on cellular GSH content, and show that JS-K markedly depletes GSH, due to JS-K's rapid uptake and cascading release of NO and reactive nitrogen species. The depletion of GSH results in alterations in the redox potential of the cellular environment, initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing agent N-acetylcysteine prevented the signaling events that lead to apoptosis. These data indicate that multiplicative depletion of the reduced glutathione pool and deregulation of intracellular redox balance are important initial steps in the mechanism of JS-K's cytotoxic action.

  20. Akt inhibitor MK-2206 promotes anti-tumor activity and cell death by modulation of AIF and Ezrin in colorectal cancer

    International Nuclear Information System (INIS)

    There is extensive evidence for the role of aberrant cell survival signaling mechanisms in cancer progression and metastasis. Akt is a major component of cell survival-signaling mechanisms in several types of cancer. It has been shown that activated Akt stabilizes XIAP by S87 phosphorylation leading to survivin/XIAP complex formation, caspase inhibition and cytoprotection of cancer cells. We have reported that TGFβ/PKA/PP2A-mediated tumor suppressor signaling regulates Akt phosphorylation in association with the dissociation of survivin/XIAP complexes leading to inhibition of stress-dependent induction of cell survival. IGF1R-dependent colon cancer cells (GEO and CBS) were used for the study. Effects on cell proliferation and cell death were determined in the presence of MK-2206. Xenograft studies were performed to determine the effect of MK-2206 on tumor volume. The effect on various cell death markers such as XIAP, survivin, AIF, Ezrin, pEzrin was determined by western blot analysis. Graph pad 5.0 was used for statistical analysis. P < 0.05 was considered significant. We characterized the mechanisms by which a novel Akt kinase inhibitor MK-2206 induced cell death in IGF1R-dependent colorectal cancer (CRC) cells with upregulated PI3K/Akt signaling in response to IGF1R activation. MK-2206 treatment generated a significant reduction in tumor growth in vivo and promoted cell death through two mechanisms. This is the first report demonstrating that Akt inactivation by MK-2206 leads to induction of and mitochondria-to-nuclear localization of the Apoptosis Inducing Factor (AIF), which is involved in caspase-independent cell death. We also observed that exposure to MK-2206 dephosphorylated Ezrin at the T567 site leading to the disruption of Akt-pEzrin-XIAP cell survival signaling. Ezrin phosphorylation at this site has been associated with malignant progression in solid tumors. The identification of these 2 novel mechanisms leading to induction of cell death indicates

  1. You have no Choice but to go on: How Physicians and Midwives in Ghana Cope with High Rates of Perinatal Death.

    Science.gov (United States)

    Petrites, Alissa D; Mullan, Patricia; Spangenberg, Kathryn; Gold, Katherine J

    2016-07-01

    Objectives Healthcare providers in low-resource settings confront high rates of perinatal mortality. How providers cope with such challenges can affect their well-being and patient care; we therefore sought to understand how physicians and midwives make sense of and cope with these deaths. Methods We conducted semi-structured interviews with midwives, obstetrician-gynecologists, pediatricians and trainee physicians at a large teaching hospital in Kumasi, Ghana. Interviews focused on participants' coping strategies surrounding perinatal death. We identified themes from interview transcripts using qualitative content analysis. Results Thirty-six participants completed the study. Themes from the transcripts revealed a continuum of control/self-efficacy and engagement with the deaths. Providers demonstrated a commitment to push on with their work and provide the best care possible. In select cases, they described the transformative power of attitude and sought to be agents of change. Conclusions Physicians and midwives in a low-resource country in sub-Saharan Africa showed remarkable resiliency in coping with perinatal death. Still, future work should focus on training clinicians in coping and strengthening their self-efficacy and engagement. PMID:26987854

  2. Systems biology modeling reveals a possible mechanism of the tumor cell death upon oncogene inactivation in EGFR addicted cancers.

    Directory of Open Access Journals (Sweden)

    Jian-Ping Zhou

    Full Text Available Despite many evidences supporting the concept of "oncogene addiction" and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK and phosphoinositol-3 kinase (PI3K/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential due to the elevated level of reactive oxygen species (ROS is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers.

  3. Inhibitory effect of snake venom toxin on NF-κB activity prevents human cervical cancer cell growth via increase of death receptor 3 and 5 expression.

    Science.gov (United States)

    Lee, Hye Lim; Park, Mi Hee; Hong, Ji Eun; Kim, Dae Hwan; Kim, Ji Young; Seo, Hyen Ok; Han, Sang-Bae; Yoon, Joo Hee; Lee, Won Hyoung; Song, Ho Sueb; Lee, Ji In; Lee, Ung Soo; Song, Min Jong; Hong, Jin Tae

    2016-02-01

    We previously found that snake venom toxin inhibits nuclear factor kappa B (NF-κB) activity in several cancer cells. NF-κB is implicated in cancer cell growth and chemoresistance. In our present study, we investigated whether snake venom toxin (SVT) inhibits NF-κB, thereby preventing human cervical cancer cell growth (Ca Ski and C33A). SVT (0-12 μg/ml) inhibited the growth of cervical cancer cells by the induction of apoptotic cell death. These inhibitory effects were associated with the inhibition of NF-κB activity. However, SVT dose dependently increased the expression of death receptors (DRs): DR3, DR5 and DR downstream pro-apoptotic proteins. Exploration of NF-κB inhibitor (Phenylarsine oxide, 0.1 μM) synergistically further increased SVT-induced DR3 and DR5 expressions accompanied with further inhibition of cancer cells growth. Moreover, deletion of DR3 and DR5 by small interfering RNA significantly abolished SVT-induced cell growth inhibitory effects, as well as NF-κB inactivation. Using TNF-related apoptosis-inducing ligand resistance cancer cells (A549 and MCF-7), we also found that SVT enhanced the susceptibility of chemoresistance of these cancer cells through down-regulation of NF-κB, but up-regulation of DR3 and DR5. In vivo study also showed that SVT (0.5 and 1 mg/kg) inhibited tumor growth accompanied with inactivation of NF-κB. Thus, our present study indicates that SVT could be applicable as an anticancer agent for cervical cancer, or as an adjuvant agent for chemoresistant cancer cells. PMID:25417048

  4. RELATIONSHIP BETWEEN THE INCIDENCE RATES OF TESTICULAR AND PROSTATIC CANCERS AND FOOD CONSUMPTIONS

    Institute of Scientific and Technical Information of China (English)

    李湘鸣; 刘秀梵; 佐藤·章夫

    2002-01-01

    Objective: To determine the relationships between the incidence rates of testicular and prostatic cancers and food consumptions in order to study the etiologic cause and the mechanism of the development of male genital organ cancer. Methods: The incidence rates of testicular and prostatic cancers in 42 countries (region) were correlated with the dietary practices in these countries. These data came from the cancer rate database (1988-1992) and the food supply database (1961-1990) provided by the Department of Environmental Health, Medical University of Yamanashi, Japan. Results: The incidence rates of testicular and prostatic cancers varied greatly from country to country but in China the rates of the both malignancies were lower than that of USA and Japan. This may be due to the difference in lifestyle, especially in dietary practices. Among the food items weexamined, cheese was most closely correlated with the incidence of testicular cancer at ages 20-39, followed by animal fats and milk. The correlation coefficient (r) was the highest (r= 0.804) when calculated for cheese consumed during the period of 1961-1965 (maternal or prepubertal consumption). Stepwise- multiple-regression analysis revealed that cheese (1961-1965) made a significant contribution to the incidence of testicular cancer. Multiple coefficient ( r) is 0.920. As far as prostatic cancer was concerned, milk was most closely correlated (r=0.711) with its incidence, followed by meat and coffee. Stepwise-multiple-regression analysis identified milk, meat, butter and coffee as significant factors contributing to the incidence of prostatic cancer (R=0.993).The results of our study suggest a role of milk and dairy practices in the development of testicular and prostatic cancers.

  5. Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ulf Geisen

    2015-07-01

    Full Text Available Pancreatic cancer is one of the most aggressive cancer entities, with an extremely poor 5-year survival rate. Therefore, novel therapeutic agents with specific modes of action are urgently needed. Marine organisms represent a promising source to identify new pharmacologically active substances. Secondary metabolites derived from marine algae are of particular interest. The present work describes cellular and molecular mechanisms induced by an HPLC-fractionated, hydrophilic extract derived from the Baltic brown seaweed Fucus vesiculosus (Fv1. Treatment with Fv1 resulted in a strong inhibition of viability in various pancreatic cancer cell lines. This extract inhibited the cell cycle of proliferating cells due to the up-regulation of cell cycle inhibitors, shown on the mRNA (microarray data and protein level. As a result, cells were dying in a caspase-independent manner. Experiments with non-dividing cells showed that proliferation is a prerequisite for the effectiveness of Fv1. Importantly, Fv1 showed low cytotoxic activity against non-malignant resting T cells and terminally differentiated cells like erythrocytes. Interestingly, accelerated killing effects were observed in combination with inhibitors of autophagy. Our in vitro data suggest that Fv1 may represent a promising new agent that deserves further development towards clinical application.

  6. Cancer Control in Bangladesh

    OpenAIRE

    Hussain, Syed Akram; Sullivan, Richard

    2013-01-01

    Cancer is predicted to be an increasingly important cause of morbidity and mortality in Bangladesh in the next few decades. The estimated incidence of 12.7 million new cancer cases will rise to 21.4 million by 2030. More than two-thirds of the total expenditure on health is through out-of-pocket payments. According to the Bangladesh Bureau of Statistics, cancer is the sixth leading cause of death. International Agency for Research on Cancer has estimated cancer-related death rates in Banglade...

  7. Stochastic model for computer simulation of the number of cancer cells and lymphocytes in homogeneous sections of cancer tumors

    CERN Document Server

    Castellanos-Moreno, Arnulfo; Corella-Madueño, Adalberto; Gutiérrez-López, Sergio; Rosas-Burgos, Rodrigo

    2014-01-01

    We deal with a small enough tumor section to consider it homogeneous, such that populations of lymphocytes and cancer cells are independent of spatial coordinates. A stochastic model based in one step processes is developed to take into account natural birth and death rates. Other rates are also introduced to consider medical treatment: natural birth rate of lymphocytes and cancer cells; induced death rate of cancer cells due to self-competition, and other ones caused by the activated lymphocytes acting on cancer cells. Additionally, a death rate of cancer cells due to induced apoptosis is considered. Weakness due to the advance of sickness is considered by introducing a lymphocytes death rate proportional to proliferation of cancer cells. Simulation is developed considering different combinations of the parameters and its values, so that several strategies are taken into account to study the effect of anti-angiogenic drugs as well the self-competition between cancer cells. Immune response, with the presence ...

  8. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells

    DEFF Research Database (Denmark)

    Frankel, Lisa; Christoffersen, Nanna R; Jacobsen, Anders; Lindow, Morten; Krogh, Anders; Lund, Anders Henrik

    2008-01-01

    MicroRNAs are emerging as important regulators of cancer-related processes. The miR-21 microRNA is overexpressed in a wide variety of cancers and has been causally linked to cellular proliferation, apoptosis, and migration. Inhibition of mir-21 in MCF-7 breast cancer cells causes reduced cell...... growth. Using array expression analysis of MCF-7 cells depleted of miR-21, we have identified mRNA targets of mir-21 and have shown a link between miR-21 and the p53 tumor suppressor protein. We furthermore found that the tumor suppressor protein Programmed Cell Death 4 (PDCD4) is regulated by miR-21 and...... demonstrated that PDCD4 is a functionally important target for miR-21 in breast cancer cells....

  9. Rates of TBI-related Emergency Department Visits, Hospitalizations, and Deaths by Sex — United States, 2001–2010

    Data.gov (United States)

    U.S. Department of Health & Human Services — Overall rates of TBI climbed slowly from 2001 through 2007, then spiked sharply in 2008 and continued to climb through 2010. The increase in TBI rates in 2008 was...

  10. Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate

    Science.gov (United States)

    Zimmerman, M. Bridget; Mahajan, Vinit B.; Bassuk, Alexander G.

    2016-01-01

    Autism spectrum disorder (ASD) is one phenotypic aspect of many monogenic, hereditary cancer syndromes. Pleiotropic effects of cancer genes on the autism phenotype could lead to repurposing of oncology medications to treat this increasingly prevalent neurodevelopmental condition for which there is currently no treatment. To explore this hypothesis we sought to discover whether autistic patients more often have rare coding, single-nucleotide variants within tumor suppressor and oncogenes and whether autistic patients are more often diagnosed with neoplasms. Exome-sequencing data from the ARRA Autism Sequencing Collaboration was compared to that of a control cohort from the Exome Variant Server database revealing that rare, coding variants within oncogenes were enriched for in the ARRA ASD cohort (p<1.0x10-8). In contrast, variants were not significantly enriched in tumor suppressor genes. Phenotypically, children and adults with ASD exhibited a protective effect against cancer, with a frequency of 1.3% vs. 3.9% (p<0.001), but the protective effect decreased with age. The odds ratio of neoplasm for those with ASD relative to controls was 0.06 (95% CI: 0.02, 0.19; p<0.0001) in the 0 to 14 age group; 0.35 (95% CI: 0.14, 0.87; p = 0.024) in the 15 to 29 age group; 0.41 (95% CI: 0.15, 1.17; p = 0.095) in the 30 to 54 age group; and 0.49 (95% CI: 0.14, 1.74; p = 0.267) in those 55 and older. Both males and females demonstrated the protective effect. These findings suggest that defects in cellular proliferation, and potentially senescence, might influence both autism and neoplasm, and already approved drugs targeting oncogenic pathways might also have therapeutic value for treating autism. PMID:26934580

  11. Influência de elementos climáticos na mortalidade de cidades brasileiras Climatic factors and total death-rates in brazilian cities

    Directory of Open Access Journals (Sweden)

    João de Barros Barreto

    1946-03-01

    Full Text Available In this paper, preliminary to a series of investigations that the A. has the purpose to make about the influence of climatic factors particularly upon the prevalence of the most important acute infectious diseases in Brazil, he raises the question whether such factors do affect in this country the total death rates, as it is reasonable to suppose, according to what has been observed in temperate zones of northern and southern hemispheres. The inclusion of absolute humidity among other climatic factors to be dealt with seems justifiable according to Rogers and Stallybrass. Owing to scarcety of reliable data the A. was obliged to limit to a five-years period (1940-1944 the complete proposed investigation, which includes seven of the most important cities, scattered throughout the brazilian territory, from north to south - Belém, recife, Salvador, Rio, S. Paulo, Curitiba and Porto Alegre. Reference is made to their normal climatic conditions and monthly death-rates variations with their mean values and standard deviations. In a first part dealing with seasonal variations only for purposes of comparison, he points out that in there tropical cities of Brazil, without very clear seasonal differentiation, the curve of general mortality reached its highest point in austral autumn season and the remaining four (including Rio near the tropic in the spring, with the exception of Curitiba, where the peak coincided with the summer season. He shows how such important causes of deaths, as diarrheas, common respiratory diseases and tuberculosis, whose seasonal distribution for each one of the seven cities is referred, may explain such seasonal variations. On a second part, a study is made of the general mortality distribution by four-months periods selected in accordance respectively with the highest or lowest values of rainfall and of mean temperature and humidity during period 1940-1944. Finally he compares the monthly waves of such climatic factors and the

  12. Histone deacetylase inhibitor-induced cell death in bladder cancer is associated with chromatin modification and modifying protein expression: A proteomic approach.

    Science.gov (United States)

    Li, Qingdi Quentin; Hao, Jian-Jiang; Zhang, Zheng; Hsu, Iawen; Liu, Yi; Tao, Zhen; Lewi, Keidren; Metwalli, Adam R; Agarwal, Piyush K

    2016-06-01

    The Cancer Genome Atlas (TCGA) project recently identified the importance of mutations in chromatin remodeling genes in human carcinomas. These findings imply that epigenetic modulators might have a therapeutic role in urothelial cancers. To exploit histone deacetylases (HDACs) as targets for cancer therapy, we investigated the HDAC inhibitors (HDACIs) romidepsin, trichostatin A, and vorinostat as potential chemotherapeutic agents for bladder cancer. We demonstrate that the three HDACIs suppressed cell growth and induced cell death in the bladder cancer cell line 5637. To identify potential mechanisms associated with the anti-proliferative and cytotoxic effects of the HDACIs, we used quantitative proteomics to determine the proteins potentially involved in these processes. Our proteome studies identified a total of 6003 unique proteins. Of these, 2472 proteins were upregulated and 2049 proteins were downregulated in response to HDACI exposure compared to the untreated controls (P<0.05). Bioinformatic analysis further revealed that those differentially expressed proteins were involved in multiple biological functions and enzyme-regulated pathways, including cell cycle progression, apoptosis, autophagy, free radical generation and DNA damage repair. HDACIs also altered the acetylation status of histones and non-histone proteins, as well as the levels of chromatin modification proteins, suggesting that HDACIs exert multiple cytotoxic actions in bladder cancer cells by inhibiting HDAC activity or altering the structure of chromatin. We conclude that HDACIs are effective in the inhibition of cell proliferation and the induction of apoptosis in the 5637 bladder cancer cells through multiple cell death-associated pathways. These observations support the notion that HDACIs provide new therapeutic options for bladder cancer treatment and thus warrant further preclinical exploration. PMID:27082124

  13. Survival advantages conferred to colon cancer cells by E-selectin-induced activation of the PI3K-NFκB survival axis downstream of Death receptor-3

    International Nuclear Information System (INIS)

    Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to endothelial cells. It requires interactions between adhesion receptors on endothelial cells and their counter-receptors on cancer cells. Notably, E-selectin, a major endothelial adhesion receptor, interacts with Death receptor-3 present on metastatic colon carcinoma cells. This interaction confers metastatic properties to colon cancer cells by promoting the adhesion of cancer cells to endothelial cells and triggering the activation of the pro-migratory p38 and pro-survival ERK pathways in the cancer cells. In the present study, we investigated further the mechanisms by which the E-selectin-activated pathways downstream of DR3 confer a survival advantage to colon cancer cells. Cell survival has been ascertained by using the WST-1 assay and by evaluating the activation of the PI3 kinase/NFκB survival axis. Apoptosis has been assayed by determining DNA fragmentation by Hoechst staining and by measuring cleavage of caspases-8 and -3. DR3 isoforms have been identified by PCR. For more precise quantification, targeted PCR reactions were carried out, and the amplified products were analyzed by automated chip-based microcapillary electrophoresis on an Agilent 2100 Bioanalyzer instrument. Interaction between DR3-expressing HT29 colon carcinoma cells and E-selectin induces the activation of the PI3K/Akt pathway. Moreover, p65/RelA, the anti-apoptotic subunit of NFκB, is rapidly translocated to the nucleus in response to E-selectin. This translocation is impaired by the PI3K inhibitor LY294002. Furthermore, inhibition of the PI3K/Akt pathway increases the cleavage of caspase 8 in colon cancer cells treated with E-selectin and this effect is still further increased when both ERK and PI3K pathways are concomitantly inhibited. Intriguingly, metastatic colon cancer cell lines such as HT29 and SW620 express higher levels of a splice variant of

  14. Survival advantages conferred to colon cancer cells by E-selectin-induced activation of the PI3K-NFκB survival axis downstream of Death receptor-3

    Directory of Open Access Journals (Sweden)

    Paquet Éric R

    2011-07-01

    Full Text Available Abstract Background Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to endothelial cells. It requires interactions between adhesion receptors on endothelial cells and their counter-receptors on cancer cells. Notably, E-selectin, a major endothelial adhesion receptor, interacts with Death receptor-3 present on metastatic colon carcinoma cells. This interaction confers metastatic properties to colon cancer cells by promoting the adhesion of cancer cells to endothelial cells and triggering the activation of the pro-migratory p38 and pro-survival ERK pathways in the cancer cells. In the present study, we investigated further the mechanisms by which the E-selectin-activated pathways downstream of DR3 confer a survival advantage to colon cancer cells. Methods Cell survival has been ascertained by using the WST-1 assay and by evaluating the activation of the PI3 kinase/NFκB survival axis. Apoptosis has been assayed by determining DNA fragmentation by Hoechst staining and by measuring cleavage of caspases-8 and -3. DR3 isoforms have been identified by PCR. For more precise quantification, targeted PCR reactions were carried out, and the amplified products were analyzed by automated chip-based microcapillary electrophoresis on an Agilent 2100 Bioanalyzer instrument. Results Interaction between DR3-expressing HT29 colon carcinoma cells and E-selectin induces the activation of the PI3K/Akt pathway. Moreover, p65/RelA, the anti-apoptotic subunit of NFκB, is rapidly translocated to the nucleus in response to E-selectin. This translocation is impaired by the PI3K inhibitor LY294002. Furthermore, inhibition of the PI3K/Akt pathway increases the cleavage of caspase 8 in colon cancer cells treated with E-selectin and this effect is still further increased when both ERK and PI3K pathways are concomitantly inhibited. Intriguingly, metastatic colon cancer cell lines such as HT

  15. Enhancement of paclitaxel-induced breast cancer cell death via the glycogen synthase kinase-3β-mediated B-cell lymphoma 2 regulation

    Science.gov (United States)

    Noh, Kyung Tae; Cha, Gil Sun; Kang, Tae Heung; Cho, Joon; Jung, In Duk; Kim, Kwang-Youn; Ahn, Soon-Cheol; You, Ji Chang; Park, Yeong-Min

    2016-01-01

    Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine protein kinase that is known to mediate cancer cell death. Here, we show that B-cell lymphoma 2 (Bcl-2), an anti-apoptotic protein, is regulated by GSK-3β and that GSK-3β-mediated regulation of Bcl-2 is crucial for mitochondrial-dependent cell death in paclitaxel-stimulated cells. We demonstrate that MCF7 GSK-3β siRNA cells are more sensitive to cell death than MCF7 GFP control cells and that in the absence of GSK-3β, Bcl-2 levels are reduced, a result enhanced by paclitaxel. Paclitaxel-induced JNK (c-Jun N-terminal kinase) activation is critical for Bcl-2 modulation. In the absence of GSK-3β, Bcl-2 was unstable in an ubiquitination-dependent manner in both basal- and paclitaxel-treated cells. Furthermore, we demonstrate that GSK-3β-mediated regulation of Bcl-2 influences cytochrome C release and mitochondrial membrane potential. Taken together, our data suggest that GSK-3β-dependent regulation of Bcl-2 is crucial for mitochondria-dependent cell death in paclitaxel-mediated breast cancer therapy. [BMB Reports 2016; 49(1): 51-56] PMID:26246283

  16. Role of autophagy in the ω-3 long chain polyunsaturated fatty acid-induced death of lung cancer A549 cells

    OpenAIRE

    Yao, Qinghua; Fu, Ting; Wang, Lu; LAI, YUEBIAO; Wang, Yuqi; Xu, Chao; Huang, Lulu; Guo, Yong

    2015-01-01

    The present study identified that ω-3 long chain polyunsaturated fatty acids (ω-3 PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) demonstrate anti-proliferative effects in lung cancer A549 cells. MTS and cytotoxicity assays were conducted to confirm that ω-3 PUFAs induced cell death. Autophagy-associated gene and signaling pathways were also detected. Microtubule-associated protein light chain 3 (LC3) expression was found to be increased subsequent to treatment with DHA and...

  17. Low heart rate variability and cancer-related fatigue in breast cancer survivors

    OpenAIRE

    Crosswell, Alexandra D.; Lockwood, Kimberly G.; Ganz, Patricia A.; Bower, Julienne E.

    2014-01-01

    Cancer-related fatigue is a common and often long lasting symptom for many breast cancer survivors. Fatigued survivors show evidence of elevated inflammation, but the physiological mechanisms driving inflammatory activity have not been determined. Alterations in the autonomic nervous system, and particularly parasympathetic nervous system activity, are a plausible, yet understudied contributor to cancer-related fatigue. The goal of this study was to replicate one previous study showing an ass...

  18. Trends in Incidence Rates of Tobacco-Related Cancer, Selected Areas, SEER Program, United States, 1992-2004

    OpenAIRE

    Polednak, Anthony P.

    2008-01-01

    Introduction Recent trends in incidence rates for tobacco-related cancers may vary geographically because of variation in socioeconomic status and in history of comprehensive state tobacco control programs (starting with California in 1989). Recent trends in risk factors are likely to affect cancer incidence rates at the youngest ages. Methods Trends in age-adjusted incidence rates for cancers most strongly associated with tobacco (ie, lung, oral cavity-pharynx, and bladder cancers) were anal...

  19. Early apoptosis and cell death induced by ATX-S10Na ( Ⅱ)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Makoto Mitsunaga; Akihito Tsubota; Kohichi Nariai; Yoshihisa Namiki; Makoto Sumi; Tetsuya Yoshikawa; Kiyotaka Fujise

    2007-01-01

    AIM: To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na (Ⅱ).METHODS: HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin V assays, transmission electron microscopy assays, caspase assays and western blotting.RESULTS: Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-XL,were decreased in Bax- and p53-independent manner.CONCLUSION: Our results indicate that early apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizingphotosensitizer ATX-S10Na (Ⅱ) are mediated by p53-Bax network and Iow levels of Bcl-2 and Bcl-XL proteins.Our results might help in formulating new therapeutic approaches in photedynamic therapy.

  20. Beclin-1-independent autophagy mediates programmed cancer cell death through interplays with endoplasmic reticulum and/or mitochondria in colbat chloride-induced hypoxia.

    Science.gov (United States)

    Sun, Lei; Liu, Ning; Liu, Shan-Shan; Xia, Wu-Yan; Liu, Meng-Yao; Li, Lin-Feng; Gao, Jian-Xin

    2015-01-01

    Autophagy has dual functions in cell survival and death. However, the effects of autophagy on cancer cell survival or death remain controversial. In this study, we show that Autophagy can mediate programmed cell death (PCD) of cancer cells in responding to cobalt chloride (CoCl2)-induced hypoxia in a Beclin-1-independent but autophagy protein 5 (ATG5)-dependent manner. Although ATG5 is not directly induced by CoCl2, its constitutive expression is essential for CoCl2-induced PCD. The ATG5-mediated autophagic PCD requires interplays with endoplasmic reticulum (ER) and/or mitochondria. In this process, ATG5 plays a central role in regulating ER stress protein CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) and mitochondrial protein second mitochondria derived activator of caspases (Smac). Two pathways for autophagic PCD in cancer cells responding to hypoxia have been identified: ATG5/CHOP/Smac pathway and ATG5/Smac pathway, which are probably dependent on the context of cell lines. The former is more potent than the latter for the induction of PCD at the early stage of hypoxia, although the ultimate efficiency of both pathways is comparable. In addition, both pathways may require ATG5-mediated conversion of LC3-I into LC3-II. Therefore, we have defined two autophagy-mediated pathways for the PCD of cancer cells in hypoxia, which are dependent on ATG5, interplayed with ER and mitochondria and tightly regulated by hypoxic status. The findings provide a new evidence that autophagy may inhibit tumor cell proliferation through trigger of PCD, facilitating the development of novel anti-cancer drugs. PMID:26609472

  1. Intraoperative radiotherapy combined with resection for pancreatic cancer. Analysis of survival rates and prognostic factors

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the efficiency of intraoperative radiotherapy (IORT) combined with surgical resection. Subjects were consecutive 69 patients with pancreatic cancer treated with surgery alone (n=31) or surgical resection combined with IORT (n=38) in a 13 year period between 1991 and 2003. We evaluated the effects of IORT against local recurrence of cancer and patients' survival, retrospectively. Furthermore, clinicopathological factors affecting the 5-year survival rate in the two groups were comparatively investigated. The IORT group showed a significantly lower local recurrence rate of cancer than that in the surgery alone group (7.8% and 22.6%, respectively; p<0.05). The 5-year survival probability in the IORT group was significantly higher than that in the surgery alone group (29.9% and 3.4%, respectively; p<0.05). According to the Japanese classification of pancreatic cancer, cancers located in the pancreas body or tail, no local residual cancer post operative procedure (R0), low grade local cancer progression (t1, 2), and low grade intrapancreatic neural invasion (ne0, 1) were significantly better prognostic factors in the IORT group than those in the surgery alone group. There were no significant differences between the both groups in the 5-year survival rate in terms of the sex of the patients, cancer of the pancreas head, histological type, more than R1, the presence of lymph node involvement, ne2-3, and clinical stages. IORT is a useful intraoperative adjuvant therapy for pancreatic cancer, when the curative resection is achieved. Our data have suggested that IORT suppresses the local recurrence of cancer and provides the significant survival benefit for those patients. (author)

  2. Toward a better understanding of the comparatively high prostate cancer incidence rates in Utah

    Directory of Open Access Journals (Sweden)

    Wiggins Charles L

    2003-04-01

    Full Text Available Abstract Background This study assesses whether comparatively high prostate cancer incidence rates among white men in Utah represent higher rates among members of the Church of Jesus Christ of Latter-day Saints (LDS or Mormons, who comprise about 70% of the state's male population, and considers the potential influence screening has on these rates. Methods Analyses are based on 14,693 histologically confirmed invasive prostate cancer cases among men aged 50 years and older identified through the Utah Cancer Registry between 1985 and 1999. Cancer records were linked to LDS Church membership records to determine LDS status. Poisson regression was used to derive rate ratios of LDS to nonLDS prostate cancer incidence, adjusted for age, disease stage, calendar time, and incidental detection. Results LDS men had a 31% (95% confidence interval, 26% – 36% higher incidence rate of prostate cancer than nonLDS men during the study period. Rates were consistently higher among LDS men over time (118% in 1985–88, 20% in 1989–92, 15% in 1993–1996, and 13% in 1997–99; age (13% in ages 50–59, 48% in ages 60–69, 28% in ages 70–79, and 16% in ages 80 and older; and stage (36% in local/regional and 17% in unstaged. An age- and stage-shift was observed for both LDS and nonLDS men, although more pronounced among LDS men. Conclusions Comparatively high prostate cancer incidence rates among LDS men in Utah are explained, at least in part, by more aggressive screening among these men.

  3. Outcomes of low-dose-rate brachytherapy for treatment of tongue cancer

    International Nuclear Information System (INIS)

    Between 1997 and 2006, 324 patients with T1-2 tongue cancer were treated with low-dose-rate brachytherapy at Tokyo Medical and Dental University Hospital. Their 5- and 10-year local control rates were 83% and 80%, respectively, and the occurrence rates of ≥ grade 3 mucositis and osteonecrosis were both 0.3%. During the study period, 9 other patients with tongue cancer underwent surgery and brachytherapy for positive surgical margins at our institution. Their 5- and 10-year local control rates were 76% and 64%. Moreover, 24 patients with tongue cancer received chemotherapy followed by brachytherapy, and their 5- and 10-year local control rates were both 100%. These outcomes are comparable to those of the patients who underwent low-dose-rate brachytherapy for T1-2 tongue cancer. In this study, 80% of patients treated by brachytherapy for T1-2 tongue cancer were cured with preserved function. However, for some patients with tumors unsuitable for treatment by brachytherapy alone, a combination of brachytherapy and surgery or chemotherapy may be a suitable treatment option. (author)

  4. High resolution anoscopy may be useful in achieving reductions in anal cancer local disease failure rates.

    Science.gov (United States)

    Goon, P; Morrison, V; Fearnhead, N; Davies, J; Wilson, C; Jephcott, C; Sterling, J; Crawford, R

    2015-05-01

    Anal cancer is uncommon, with an incidence rate of 0.5-1.0 per 100,000 of the population but incidence rates have been steadily increasing over the last 3 decades. Biological and epidemiological evidence have been mounting and demonstrate that anal cancer has many similarities to cervical cancer, especially in regard to its aetiology. High-resolution anoscopy (HRA) of the anal region – analogous to colposcopy of the cervix, is a technique that is not well-known in the medical and surgical fraternity. Evidence to support the use of HRA for detection and treatment in the surveillance of AIN exists and strongly suggests that it is beneficial, resulting in reduced rates of cancer progression. Pilot data from our study showed a local disease failure rate of 1.73 per 1000 patient-months compared with a published rate of 9.89 per 1000 patient-months. This demonstrates a 5.72-fold reduction in local disease failure rates of patients with T1-T3 tumours; the data therefore suggests that use of HRA for detection and treatment in surveillance of anal cancer patients will help prevent local regional relapse at the anal site. There is an urgent need for a large, randomised controlled clinical trial to definitively test this hypothesis. PMID:24373061

  5. Cancer Mortality in the United States: 1970-1994 - Direct Download

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — This data set contains 1970-1994 cancer mortality information for counties in the United States. Included are death rates, number of deaths, confidence levels, and...

  6. Response Rates in Studies of Couples Coping With Cancer : A Systematic Review

    NARCIS (Netherlands)

    Dagan, Meirav; Hagedoorn, Mariet

    2014-01-01

    Objective: Recruiting couples for psychological studies can be challenging. This brief report is the first to examine the average couples' response rate and to systematically review the quality of reporting of couples' response rate in studies of couples coping with cancer. Method: A systematic revi

  7. Factors affecting rate of stroke-related death in elderly male military population A 23-year cohort study of 1 268 cases in Xi'an, China

    Institute of Scientific and Technical Information of China (English)

    Yanhua Li; Yu Sun; Xiaoyong Sai; Yao He; Qiang Wu; Yongping Yan; Ke Men; Liangshou Li

    2011-01-01

    The study is the first long-term cohort study examining stroke and its subtypes among a population of Chinese elderly male retired military veterans. We reported on a 23-year cohort study examining stroke in 1 268 elderly male patients living in Xi'an, China since 1987. The stroke-related mortality rate in this cohort was 361.50/1 × 106 per year. Cerebral hemorrhage was the dominant cause of death, with 28 cases of fatal cerebral infarction and 49 cases of fatal cerebral hemorrhage among 77 stroke-related deaths. Independent risk factors for stroke mortality included age, blood pressure, smoking, body mass index, family history of hypertension, past medical history of stroke, hypertension and hyperlipidemia. Among them, ischemic stroke mortality correlated with age, smoking, family history of hypertension and past medical history of stroke, while hemorrhagic stroke was related to blood pressure, body mass index and past medical history of hypertension. Our results indicated that maintaining appropriate levels of blood pressure and body mass, smoking cessation and prevention of hyperlipidemia can reduce the risk of stroke-related death in elderly males who are retired from military service.

  8. Moderate stem-cell telomere shortening rate postpones cancer onset in a stochastic model

    Science.gov (United States)

    Holbek, Simon; Bendtsen, Kristian Moss; Juul, Jeppe

    2013-10-01

    Mammalian cells are restricted from proliferating indefinitely. Telomeres at the end of each chromosome are shortened at cell division and when they reach a critical length, the cell will enter permanent cell cycle arrest—a state known as senescence. This mechanism is thought to be tumor suppressing, as it helps prevent precancerous cells from dividing uncontrollably. Stem cells express the enzyme telomerase, which elongates the telomeres, thereby postponing senescence. However, unlike germ cells and most types of cancer cells, stem cells only express telomerase at levels insufficient to fully maintain the length of their telomeres, leading to a slow decline in proliferation potential. It is not yet fully understood how this decline influences the risk of cancer and the longevity of the organism. We here develop a stochastic model to explore the role of telomere dynamics in relation to both senescence and cancer. The model describes the accumulation of cancerous mutations in a multicellular organism and creates a coherent theoretical framework for interpreting the results of several recent experiments on telomerase regulation. We demonstrate that the longest average cancer-free lifespan before cancer onset is obtained when stem cells start with relatively long telomeres that are shortened at a steady rate at cell division. Furthermore, the risk of cancer early in life can be reduced by having a short initial telomere length. Finally, our model suggests that evolution will favor a shorter than optimal average cancer-free lifespan in order to postpone cancer onset until late in life.

  9. Existential Concerns About Death

    DEFF Research Database (Denmark)

    Moestrup, Lene; Hansen, Helle Ploug

    2014-01-01

    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...

  10. 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...

  11. Continuous increase of cardiovascular diseases, diabetes, and non-HIV related cancers as causes of death in HIV-infected individuals in Brazil: an analysis of nationwide data.

    Directory of Open Access Journals (Sweden)

    Adelzon A Paula

    Full Text Available INTRODUCTION: After antiretroviral therapy (ART became available, there was a decline in the number of deaths in persons infected with HIV. Thereafter, there was a decrease in the proportion of deaths attributed to opportunistic infections and an increase in the proportion of deaths attributed to chronic comorbidities. Herein we extend previous observations from a nationwide survey on temporal trends in causes of death in HIV-infected patients in Brazil. METHODS: We describe temporal trends in causes of death among adults who had HIV/AIDS listed in the death certificate to those who did not. All death certificates issued in Brazil from 1999 to 2011 and listed in the national mortality database were included. Generalized linear mixed-effects logistic models were used to study temporal trends in proportions. RESULTS: In the HIV-infected population, there was an annual adjusted average increase of 6.0%, 12.0%, 4.0% and 4.1% for cancer, external causes, cardiovascular diseases (CVD and diabetes mellitus (DM, respectively, compared to 3.0%, 4.0%, 1.0% and 3.9%, in the non-HIV group. For tuberculosis (TB, there was an adjusted average increase of 0.3%/year and a decrease of 3.0%/year in the HIV and the non-HIV groups, respectively. Compared to 1999, the odds ratio (OR for cancer, external causes, CVD, DM, or TB in the HIV group were, respectively, 2.31, 4.17, 1.76, 2.27 and 1.02, while for the non-HIV group, the corresponding OR were 1.31, 1.63, 1.14, 1.62 and 0.67. Interactions between year as a continuous or categorical variable and HIV were significant (p<0.001 for all conditions, except for DM when year was considered as a continuous variable (p = 0.76. CONCLUSIONS: Non HIV-related co-morbidities continue to increase more rapidly as causes of death among HIV-infected individuals than in those without HIV infection, highlighting the need for targeting prevention measures and surveillance for chronic diseases among those patients.

  12. Active management of third stage of labour, post–partum haemorrhage and maternal death rate in the Vanga Health Zone, Province of Bandundu, Democratic Republic of the Congo

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Fina Lubaki

    2010-03-01

    Full Text Available Background: Post-partum haemorrhage (PPH is the single largest cause of maternal death worldwide and a particular burden for developing countries. In Africa, about 33.9 % of maternal deaths are due to PPH. In the Democratic Republic of the Congo (DRC, the prevalence of PPH is unknown. PPH can be prevented with active management of the third stage of labour (AMTSL. Objectives: To describe the practice of AMTSL in Vanga Health Zone and to calculate the incidence of PPH in Vanga Health Zone.Method: An intervention study with post-test-only design was conducted among health maternity wards using a data collection sheet to obtain information. All pregnant women attending Vanga Health maternity wards constituted the study population. Frequencies were determined for variables of interest.Results: From April 2007 to March 2008, 6339 deliveries took place at Vanga Health maternity wards, representing 71% of the institutional delivery rate. The number of deliveries realised with the practice of (AMTSL were 5562; 366 cases of PPH were reported, making an incidence of 5.77%. Three cases of maternal deaths – two of which were related to PPH – were reported during the study period, which means there was a decline of 70% compared with the previous two years.Conclusion: The prevalence of PPH has been estimated to be 5.77%; PPH represents the cause of 67% of all maternal deaths. The extension of AMTSL practice, combined with the assurance of better supplies of oxytocin to enhance drug management, is strongly advised/suggested. As a number of births still take place outside the health maternity wards, the introduction of oral misoprostol could be considered a part of AMTSL for use by patients being treated by traditional midwives.

  13. Centralisation of treatment and survival rates for cancer.

    OpenAIRE

    Stiller, C A

    1988-01-01

    Between 1977 and 1984 the proportion of children with malignant disease in Britain initially referred to specialist paediatric oncology centres increased from 44% to 71%. The percentage varied considerably with type of disease and region of residence. Children with acute non-lymphoblastic leukaemia, non-Hodgkin's lymphoma, Ewing's tumour, rhabdomyosarcoma, and (during 1981-84) osteosarcoma treated at paediatric oncology centres had significantly higher survival rates than those treated elsewh...

  14. Effects of dose, dose-rate and fraction on radiation-induced breast and lung cancers

    International Nuclear Information System (INIS)

    Recent results from a large Canadian epidemiologic cohort study of low-LET radiation and cancer will be described. This is a study of 64,172 tuberculosis patients first treated in Canada between 1930 and 1952, of whom many received substantial doses to breast and lung tissue from repeated chest fluoroscopies. The mortality of the cohort between 1950 and 1987 has been determined by computerized record linkage to the National Mortality Data Base. There is a strong positive association between radiation and breast cancer risk among the females in the cohort, but in contrast very little evidence of any increased risk in lung cancer. The results of this and other studies suggest that the effect of dose-rate and/or fractionation on cancer risk may will differ depending upon the particular cancer being considered. (author)

  15. Proteomic analysis of novel targets associated with the enhancement of TrkA-induced SK-N-MC cancer cell death caused by NGF

    Science.gov (United States)

    Jung, Eun Joo; Chung, Ky Hyun; Bae, Dong-Won; Kim, Choong Won

    2016-01-01

    Nerve growth factor (NGF) is known to regulate both cancer cell survival and death signaling, depending on the cellular circumstances, in various cell types. In this study, we showed that NGF strongly upregulated the protein level of tropomyosin-related kinase A (TrkA) in TrkA-inducible SK-N-MC cancer cells, resulting in increases in various TrkA-dependent cellular processes, including the phosphorylation of c-Jun N-terminal kinase (JNK) and caspase-8 cleavage. In addition, NGF enhanced TrkA-induced morphological changes and cell death, and this effect was significantly suppressed by the JNK inhibitor SP600125, but not by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin. To investigate novel targets associated with the enhancement of TrkA-induced SK-N-MC cell death caused by NGF, we performed Coomassie Brilliant Blue staining and two-dimensional (2D) proteomic analysis in TrkA-inducible SK-N-MC cells. We identified 31 protein spots that were either greatly upregulated or downregulated by TrkA during NGF treatment using matrix-associated laser desorption/ionization time of flight/time of flight mass spectrometry, and we analyzed the effects of SP600125 and wortmannin on the spots. Interestingly, 11 protein spots, including heterogeneous nuclear ribonucleoprotein K (hnRNP K), lamin B1 and TAR DNA-binding protein (TDP43), were significantly influenced by SP600125, but not by wortmannin. Moreover, the NGF/TrkA-dependent inhibition of cell viability was significantly enhanced by knockdown of hnRNP K using small interfering RNA, demonstrating that hnRNP K is a novel target associated with the regulation of TrkA-dependent SK-N-MC cancer cell death enhanced by NGF. PMID:27229480

  16. The death of marriage? The effects of new forms of legal recognition on marriage rates in the United States.

    Science.gov (United States)

    Dillender, Marcus

    2014-04-01

    Some conservative groups argue that allowing same-sex couples to marry reduces the value of marriage to opposite-sex couples. This article examines how changes in U.S. legal recognition laws occurring between 1995 and 2010 designed to include same-sex couples have altered marriage rates in the United States. Using a difference-in-differences strategy that compares how marriage rates change after legal recognition in U.S. states that alter legal recognition versus states that do not, I find no evidence that allowing same-sex couples to marry reduces the opposite-sex marriage rate. Although the opposite-sex marriage rate is unaffected by same-sex couples marrying, it decreases when domestic partnerships are available to opposite-sex couples. PMID:24481925

  17. Brain cancer mortality rates increase with Toxoplasma gondii seroprevalence in France

    Science.gov (United States)

    Vittecoq, Marion; Elguero, Eric; Lafferty, Kevin D.; Roche, Benjamin; Brodeur, Jacques; Gauthier-Clerc, Michel; Missé, Dorothée; Thomas, Frédéric

    2012-01-01

    The incidence of adult brain cancer was previously shown to be higher in countries where the parasite Toxoplasma gondii is common, suggesting that this brain protozoan could potentially increase the risk of tumor formation. Using countries as replicates has, however, several potential confounding factors, particularly because detection rates vary with country wealth. Using an independent dataset entirely within France, we further establish the significance of the association between T. gondii and brain cancer and find additional demographic resolution. In adult age classes 55 years and older, regional mortality rates due to brain cancer correlated positively with the local seroprevalence of T. gondii. This effect was particularly strong for men. While this novel evidence of a significant statistical association between T. gondii infection and brain cancer does not demonstrate causation, these results suggest that investigations at the scale of the individual are merited.

  18. Fear of Death, Mortality Communication, and Psychological Distress among Secular and Religiously Observant Family Caregivers of Terminal Cancer Patients

    Science.gov (United States)

    Bachner, Yaacov G.; O'Rourke, Norm; Carmel, Sara

    2011-01-01

    Previous research suggests that caregivers and terminally ill patients face substantial difficulties discussing illness and death. Existing research, however, has focused primarily on the experience of patients. The current study compared responses as well as the relative strength of association between mortality communication, fear of death, and…

  19. Rate of deaths due to child abuse and neglect in children 0-3 years of age in Germany.

    Science.gov (United States)

    Banaschak, Sibylle; Janßen, Katharina; Schulte, Babette; Rothschild, Markus A

    2015-09-01

    In recent years, increasing attention has been paid to the issue of (fatal) child abuse and neglect, largely due to the media attention garnered by some headline-grabbing cases. If media statements are to be believed, such cases may be an increasing phenomenon. With these published accounts in mind, publicly available statistics should be analysed with respect to the question of whether reliable statements can be formulated based on these figures. It is hypothesised that certain data, e.g., the Innocenti report published by UNICEF in 2003, may be based on unreliable data sources. For this reason, the generation of such data, and the reliability of the data itself, should also be discussed. Our focus was on publicly available German mortality and police crime statistics (Polizeiliche Kriminalstatistik). These data were classified with respect to child age, data origin, and cause of death (murder, culpable homicide, etc.). In our opinion, the available data could not be considered in formulating reliable scientific statements about fatal child abuse and neglect, given the lack of detail and the flawed nature of the basic data. Increasing the number of autopsies of children 0-3 years of age should be considered as a means to ensure the capture of valid, practical, and reliable data. This could bring about some enlightenment and assist in the development of preemptive strategies to decrease the incidence of (fatal) child abuse and neglect. PMID:25631691

  20. Association of arsenic exposure with lung cancer incidence rates in the United States.

    Directory of Open Access Journals (Sweden)

    Joseph J Putila

    Full Text Available Although strong exposure to arsenic has been shown to be carcinogenic, its contribution to lung cancer incidence in the United States is not well characterized. We sought to determine if the low-level exposures to arsenic seen in the U.S. are associated with lung cancer incidence after controlling for possible confounders, and to assess the interaction with smoking behavior.Measurements of arsenic stream sediment and soil concentration obtained from the USGS National Geochemical Survey were combined, respectively, with 2008 BRFSS estimates on smoking prevalence and 2000 U.S. Census county level income to determine the effects of these factors on lung cancer incidence, as estimated from respective state-wide cancer registries and the SEER database. Poisson regression was used to determine the association between each variable and age-adjusted county-level lung cancer incidence. ANOVA was used to assess interaction effects between covariates.Sediment levels of arsenic were significantly associated with an increase in incident cases of lung cancer (P<0.0001. These effects persisted after controlling for smoking and income (P<0.0001. Across the U.S., exposure to arsenic may contribute to up to 5,297 lung cancer cases per year. There was also a significant interaction between arsenic exposure levels and smoking prevalence (P<0.05.Arsenic was significantly associated with lung cancer incidence rates in the U.S. after controlling for smoking and income, indicating that low-level exposure to arsenic is responsible for excess cancer cases in many parts of the U.S. Elevated county smoking prevalence strengthened the association between arsenic exposure and lung cancer incidence rate, an effect previously unseen on a population level.

  1. Heart Rate Variability and Length of Survival in Hospice Cancer Patients

    OpenAIRE

    Kim, Do Hoon; Kim, Jeong A; Choi, Youn Seon; Kim, Su Hyun; Lee, June Young; Kim, Young Eun

    2010-01-01

    We examined the association between heart rate variability (HRV) and survival duration to evaluate the usefulness of HRV as a prognostic factor for hospice cancer patients. In terminally ill cancer patients who visited the Hospice clinic, we checked demographic data, Karnofsky performance scale (KPS), HRV, dyspnea, anorexia, as well as fasting blood glucose and total cholesterol. After following up their duration of survival, we examined meaningful prognostic factors for predicting life expec...

  2. Changes in heart-rate variability of survivors of nasopharyngeal cancer during Tai Chi Qigong practice

    OpenAIRE

    Fong, Shirley S.M.; Wong, Janet Y. H.; Chung, Louisa M. Y.; Yam, Timothy T.T.; Chung, Joanne W. Y.; Lee, Y.M.; Chow, Lina P. Y.; Luk, W. S.; Ng, Shamay S.M.

    2015-01-01

    [Purpose] To explore the changes in heart-rate variability (HRV) of survivors of nasopharyngeal cancer (NPC) before, during, and after a Tai Chi (TC) Qigong exercise. [Subjects and Methods] Eleven survivors of NPC participated voluntarily in the study. The heart rate of each participant was measured continuously for 1 minute before the TC Qigong intervention, during the 5-minute TC Qigong intervention, and for 1 minute after the intervention, using a Polar heart-rate monitor. Spectral HRV was...

  3. Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities.

    Science.gov (United States)

    DeSantis, Carol E; Siegel, Rebecca L; Sauer, Ann Goding; Miller, Kimberly D; Fedewa, Stacey A; Alcaraz, Kassandra I; Jemal, Ahmedin

    2016-07-01

    In this article, the American Cancer Society provides the estimated number of new cancer cases and deaths for blacks in the United States and the most recent data on cancer incidence, mortality, survival, screening, and risk factors for cancer. Incidence data are from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries, and mortality data are from the National Center for Health Statistics. Approximately 189,910 new cases of cancer and 69,410 cancer deaths will occur among blacks in 2016. Although blacks continue to have higher cancer death rates than whites, the disparity has narrowed for all cancers combined in men and women and for lung and prostate cancers in men. In contrast, the racial gap in death rates has widened for breast cancer in women and remained level for colorectal cancer in men. The reduction in overall cancer death rates since the early 1990s translates to the avoidance of more than 300,000 deaths among blacks. In men, incidence rates from 2003 to 2012 decreased for all cancers combined (by 2.0% per year) as well as for the top 3 cancer sites (prostate, lung, and colorectal). In women, overall rates during the corresponding time period remained unchanged, reflecting increasing trends in breast cancer combined with decreasing trends in lung and colorectal cancer rates. Five-year relative survival is lower for blacks than whites for most cancers at each stage of diagnosis. The extent to which these disparities reflect unequal access to health care versus other factors remains an active area of research. Progress in reducing cancer death rates could be accelerated by ensuring equitable access to prevention, early detection, and high-quality treatment. CA Cancer J Clin 2016;66:290-308. © 2016 American Cancer Society. PMID:26910411

  4. On Death

    Institute of Scientific and Technical Information of China (English)

    Zhangyan

    2016-01-01

    Death is not a terrible word, but a provoking one. Different people have different opinions, but no one can convince others of what death really means. This article made a tentative and superficial analysis on death according to the true feeing and experiences of the author. In her opinion, we needn’t consider more about death; the important for the death is how to live meaningfully.

  5. Rates of 47, + 13 amd 46 translocation D/13 Patau syndrome in live births and comparison with rates in fetal deaths and at amniocentesis.

    OpenAIRE

    Hook, E B

    1980-01-01

    Trisomy 13 (Patau syndrome) is rare in newborns. Data on rates in 167,774 live births from 17 separate studies are reviewed, and the following pooled rates found for: (1) 47,trisomy 13, 8.3 X 10(-5) (1/12,000); and (2) 46, (D/13 Robertsonian translocations), 4.2 X 10(-5) (1/24,000)--mutants, 1.2 X 10(-5) (1/80,000) to 1.8 X 10(-5) (1/56,000); and familial cases, 2.4 X 10(-5) (1/42,000) to 3.0 X 10(-5) (1/33,000). The rate of trisomy 13 (47, + 13) in liveborns (ignoring possible biases in stud...

  6. Coherence-controlled holographic microscopy enabled recognition of necrosis as the mechanism of cancer cells death after exposure to cytopathic turbid emulsion

    Science.gov (United States)

    Collakova, Jana; Krizova, Aneta; Kollarova, Vera; Dostal, Zbynek; Slaba, Michala; Vesely, Pavel; Chmelik, Radim

    2015-11-01

    Coherence-controlled holographic microscopy (CCHM) in low-coherence mode possesses a pronounced coherence gate effect. This offers an option to investigate the details of cellular events leading to cell death caused by cytopathic turbid emulsions. CCHM capacity was first assessed in model situations that showed clear images obtained with low coherence of illumination but not with high coherence of illumination. Then, the form of death of human cancer cells induced by treatment with biologically active phospholipids (BAPs) preparation was investigated. The observed overall retraction of cell colony was apparently caused by the release of cell-to-substratum contacts. This was followed by the accumulation of granules decorating the nuclear membrane. Then, the occurrence of nuclear membrane indentations signaled the start of damage to the integrity of the cell nucleus. In the final stage, cells shrunk and disintegrated. This indicated that BAPs cause cell death by necrosis and not apoptosis. An intriguing option of checking the fate of cancer cells caused by the anticipated cooperative effect after adding another tested substance sodium dichloroacetate to turbid emulsion is discussed on grounds of pilot experiments. Such observations should reveal the impact and mechanism of action of the interacting drugs on cell behavior and fate that would otherwise remain hidden in turbid milieu.

  7. Screening for cervical cancer in French Guiana: screening rates from 2006 to 2011.

    Science.gov (United States)

    Douine, M; Roué, T; Lelarge, C; Adenis, A; Thomas, N; Nacher, M

    2015-12-01

    In French Guiana, the age-standardized incidence rate of cervical cancer is four times higher than in France and the mortality rate 5.5 times higher. A survival study revealed that stage at diagnosis was the main factor influencing the prognosis, showing that early detection is crucial to increase cervical cancer survival. The present study aimed at evaluating the cervical cancer screening rate between 2006 and 2011 by age and for a 3-year period in French Guiana. All pap smears realised in French Guiana were analysed in two laboratories allowing exhaustive review of screening data. The screening rate was estimated at about 54% from 2006 to 2011, with a statistical difference between coastal and rural area (56.3% versus 18.7%). Although the methodological difference did not allow comparisons with metropolitan France, these results could be used to evaluate the impact of organised cervical cancer screening by the French Guiana Association for Organized Screening of Cancers which has been implemented in French Guiana since 2012. PMID:26608273

  8. Early assessment of heart rate variability is predictive of in-hospital death and major complications during acute myocardial infarction

    OpenAIRE

    Carpeggiani, Clara; Emdin, Michele; Landi, Patrizia; Michelassi, Claudio; L'Abbate, Antonio

    2003-01-01

    Background: Depressed heart rate variability (HRV) at AMI discharge is associated with poor Iong-lerm prognosis However, its early (< 48 hours) prediclive value has not been exlensively investigaled Aim of the sludy was to invest igale, during acute myocardial infarction (AMI), in hospital prognostic value of HRV.

  9. [Cancer].

    Science.gov (United States)

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer. PMID:27603890

  10. Duration of short-course androgen suppression therapy and the risk of death as a result of prostate cancer.

    LENUS (Irish Health Repository)

    D'Amico, Anthony V

    2011-12-10

    We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer-specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories.

  11. Effects of hypoxia-inducible factor-1α on radiation-induced autophagic cell death in breast cancer cells

    International Nuclear Information System (INIS)

    Objective: To study the effects of hypoxia-inducible factor-1α (HIF-1α) on radiation-induced autophagic cell death in breast cancer cells. Methods: MCF-7 cells were divided into four groups:control (normoxia,21% Oxygen),irradiation (8 Gy X-rays), hypoxia (Cobalt chloride, CoCl2) and irradiation with hypoxia (CoCl2). 150 μmol/L CoCl2 was utilized to induce hypoxic conditions. Western blot was applied to detect the expression of HIF-1α and MAPLC3. MDC and Hoechst staining were used to detect autophagy and apoptosis. Radiosensitivity was detected by cloning formation. The short hairpin interfering RNA (shRNA) retroviral transduction particles targeting HIF-1α was transfected into MCF-7 cells to establish HIF-1α knockdown cells, then the radiosensibility, autophagy and apoptosis were detected. Results: Compared with control group and irradiation group,the protein level of HIF-1 increased obviously in the normoxia, irradiation, hypoxia and irradiation with hypoxia groups, and the values were 0, 0, 1.00, 1.89, respectively. The expression levels of MAPLC3 were markedly up-regulated in irradiation, hypoxia and irradiation with hypoxia groups as compared with control, and the ratios of LC3Ⅱ/LC3Ⅰ were 1.15, 1.73, 2.38 and 3.60, respectively. The radiosensitivity of MCF-7 cells decreased in the following order:normoxia with 3MA > normoxia > hypoxia with 3MA > hypoxia. HIF-1α knockdown cell (pSUPER-HIF-1α Ri) and vector control were constructed. After treatment with CoCl2, survival fraction of MCF-7-pSUPER was significantly higher than that of control (t=3.080, 6.946, 6.658, 6.380, P<0.05), and radiosensitivity was down-regulated after irradiation,but there was no significant difference between normoxia and hypoxia in survival fraction of MCF-7-pSUPER-HIF-1α Ri. After treatment of irradiation or hypoxia, the autophagic fractions in MCF-7-pSUPER-HIF-1α Ri significantly decreased, reduced by 21.1%, 25.5%, 15.5%, respectively (t=4.635, 4.738, 6.354, P<0.05) as

  12. The correlation between rates of cancer and autism: an exploratory ecological investigation.

    Directory of Open Access Journals (Sweden)

    Hung-Teh Kao

    Full Text Available BACKGROUND: Autism is associated with high rates of genomic aberrations, including chromosomal rearrangements and de novo copy-number variations. These observations are reminiscent of cancer, a disease where genomic rearrangements also play a role. We undertook a correlative epidemiological study to explore the possibility that shared risk factors might exist for autism and specific types of cancer. METHODOLOGY/PRINCIPAL FINDINGS: To determine if significant correlations exist between the prevalence of autism and the incidence of cancer, we obtained and analyzed state-wide data reported by age and gender throughout the United States. Autism data were obtained from the U.S. Department of Education via the Individuals with Disabilities Education Act (IDEA (2000-2007, reported annually by age group and cancer incidence data were obtained from the Centers for Disease Control and Prevention (CDC (1999-2005. IDEA data were further subdivided depending on the method used to diagnose autism (DSM IV or the Code of Federal Regulations, using strict or expanded criteria. Spearman rank correlations were calculated for all possible pairwise combinations of annual autism rates and the incidence of specific cancers. Following this, Bonferroni's correction was applied to significance values. Two independent methods for determining an overall combined p-value based on dependent correlations were obtained for each set of calculations. High correlations were found between autism rates and the incidence of in situ breast cancer (p < or = 10(-10, modified inverse chi square, n = 16 using data from states that adhere strictly to the Code of Federal Regulations for diagnosing autism. By contrast, few significant correlations were observed between autism prevalence and the incidence of 23 other female and 22 male cancers. CONCLUSIONS: These findings suggest that there may be an association between autism and specific forms of cancer.

  13. Identification of a Novel Cell Death Receptor Mediating IGFBP-3-induced Anti-tumor Effects in Breast and Prostate Cancer*

    OpenAIRE

    Ingermann, Angela R.; Yang, Yong-feng; Han, Jinfeng; Mikami, Aki; Garza, Amanda E.; Mohanraj, Lathika; Fan, Lingbo; Idowu, Michael; Ware, Joy L.; Kim, Ho-Seong; Lee, Dae-Yeol; Oh, Youngman

    2010-01-01

    Insulin-like growth factor-binding protein-3 (IGFBP-3), a major regulator of endocrine actions of IGFs, is a p53-regulated potent apoptotic factor and is significantly suppressed in a variety of cancers. Recent epidemiologic studies suggest that IGFBP-3 contributes to cancer risk protection in a variety of cancers, and a polymorphic variation of IGFBP-3 influences cancer risk, although other studies vary in their conclusions. Some antiproliferative actions of IGFBP-3 have been reported to be ...

  14. Induction of multiple programmed cell death pathways by IFN-beta in human non-small-cell lung cancer cell lines.

    Science.gov (United States)

    Zhang, H; Koty, P P; Mayotte, J; Levitt, M L

    1999-02-25

    Tissue transglutaminase (tTG) and keratinocyte transglutaminase (kTG), as well as the cross-linked envelopes (CLE) that they form, have been associated with squamous differentiation and programmed cell death in epithelial cells. When interferon-beta (IFN-beta) was used to stimulate differentiation and programmed cell death in the human lung cancer cell lines NCI-H596 and NCI-H226, the cells underwent a decrease in cellular density. In NCI-H596 IFN-beta caused an increase in kTG activity and DNA fragmentation in the lower density cells, which were significantly slower growing than control cells. However, in the higher density cells, which were only slightly slower growing than control cells, IFN-beta caused an increase in tTG activity and CLE competence. Dual-parameter flow cytometry demonstrated that IFN-beta-induced squamous differentiation preceded programmed cell death. Treatment of NCI-H596 cells with monodansylcadaverine, a transglutaminase inhibitor, prevented the increase in CLE competence, but did not inhibit DNA fragmentation. These results suggest that IFN-beta can induce NCI-H596 cells to enter multiple cell death pathways and that these pathways are not only differentiation related, but may also be growth driven. PMID:10047455

  15. Skin cancer as a marker of sun exposure associates with myocardial infarction, hip fracture and death from any cause

    DEFF Research Database (Denmark)

    Brøndum-Jacobsen, Peter; Nordestgaard, Børge G; Nielsen, Sune F;

    2013-01-01

    Sun exposure is the single most important risk factor for skin cancer, but sun exposure may also have beneficial effects on health. We tested the hypothesis that individuals with skin cancer (non-melanoma skin cancer and cutaneous malignant melanoma) have less myocardial infarction, hip fracture...

  16. Resting heart rate as a prognostic factor for mortality in patients with breast cancer.

    Science.gov (United States)

    Lee, Dong Hoon; Park, Seho; Lim, Sung Mook; Lee, Mi Kyung; Giovannucci, Edward L; Kim, Joo Heung; Kim, Seung Il; Jeon, Justin Y

    2016-09-01

    Although elevated resting heart rate (RHR) has been shown to be associated with mortality in the general population and patients with certain diseases, no study has examined this association in patients with breast cancer. A total of 4786 patients with stage I-III breast cancer were retrospectively selected from the Severance hospital breast cancer registry in Seoul, Korea. RHR was measured at baseline and the mean follow-up time for all patients was 5.0 ± 2.5 years. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated using Cox regression models. After adjustment for prognostic factors, patients in the highest quintile of RHR (≥85 beat per minute (bpm)) had a significantly higher risk of all-cause mortality (HR: 1.57; 95 %CI 1.05-2.35), breast cancer-specific mortality (HR: 1.69; 95 %CI 1.07-2.68), and cancer recurrence (HR: 1.49; 95 %CI 0.99-2.25), compared to those in the lowest quintile (≤67 bpm). Moreover, every 10 bpm increase in RHR was associated with 15, 22, and 6 % increased risk of all-cause mortality, breast cancer-specific mortality, and cancer recurrence, respectively. However, the association between RHR and cancer recurrence was not statistically significant (p = 0.26). Elevated RHR was associated with an increased risk of mortality in patients with breast cancer. The findings from this study suggest that RHR may be used as a prognostic factor for patients with breast cancer in clinical settings. PMID:27544225

  17. Constitutively active ErbB2 regulates cisplatin-induced cell death in breast cancer cells via pro- and antiapoptotic mechanisms

    DEFF Research Database (Denmark)

    Sigurðsson, Haraldur H; Olesen, Christina Wilkens; Dybboe, Rie;

    2015-01-01

    UNLABELLED: Despite the frequent expression of N-terminally truncated ErbB2 (ΔNErbB2/p95HER2) in breast cancer and its association with Herceptin resistance and poor prognosis, it remains poorly understood how ΔNErbB2 affects chemotherapy-induced cell death. Previously it was shown that ΔNErbB2...... upregulates acid extrusion from MCF-7 breast cancer cells and that inhibition of the Na(+)/H(+) exchanger (SLC9A1/NHE1) strongly sensitizes ΔNErbB2-expressing MCF-7 cells to cisplatin chemotherapy. The aim of this study was to identify the mechanism through which ΔNErbB2 regulates cisplatin-induced breast...... cancer cell death, and determine how NHE1 regulates this process. Cisplatin treatment elicited apoptosis, ATM phosphorylation, upregulation of p53, Noxa (PMAIP1), and PUMA (BBC3), and cleavage of caspase-9, -7, fodrin, and PARP-1 in MCF-7 cells. Inducible ΔNErbB2 expression strongly reduced cisplatin...

  18. Application of Artificial Neural Network in Predicting the Survival Rate of Gastric Cancer Patients

    Directory of Open Access Journals (Sweden)

    A Biglarian

    2011-06-01

    Full Text Available "nBackground: The aim of this study was to predict the survival rate of Iranian gastric cancer patients using the Cox proportional hazard and artificial neural network models as well as comparing the ability of these approaches in predicting the survival of these patients."nMethods: In this historical cohort study, the data gathered from 436 registered gastric cancer patients who have had surgery between 2002 and 2007 at the Taleghani Hospital (a referral center for gastrointestinal cancers, Tehran, Iran, to predict the survival time using Cox proportional hazard and artificial neural network techniques. "nResults: The estimated one-year, two-year, three-year, four-year and five-year survival rates of the patients were 77.9%, 53.1%, 40.8%, 32.0%, and 17.4%, respectively. The Cox regression analysis revealed that the age at diag-nosis, high-risk behaviors, extent of wall penetration, distant metastasis and tumor stage were significantly associated with the survival rate of the patients. The true prediction of neural network was 83.1%, and for Cox regression model, 75.0%."nConclusion: The present study shows that neural network model is a more powerful statistical tool in predicting the survival rate of the gastric cancer patients compared to Cox proportional hazard regression model. Therefore, this model recommended for the predicting the survival rate of these patients.

  19. A trial for improving the rate of participation in breast cancer screening

    International Nuclear Information System (INIS)

    In order to search for a good method of increasing the rate of participation in breast cancer screening, we reviewed our previous records of breast cancer screening carried out by inspection and palpation during the preceding 32-year period. Screening by mammography was started in 2004, and in the following year became employed in all districts of Kochi Prefecture. When mammography screening began, we hoped that the participation rate would be at least 20%, which was the level when breast cancer screening was performed by inspection and palpation. In fact, the participation rate was as high as 27.6% in the period 2004-2005, and the breast cancer detection rate was 0.38%. We think that this high participation rate was achieved through complete transition from screening by inspection and palpation to that by mammography, offering guidance to district health nurses and local government administrative staff, education of the public about the importance of breast self-palpation, and other informative activities. (author)

  20. Decursin was Accelerated Human Lung Cancer Cell Death Caused by Proton Beam Irradiation via Blocking the p42/44 MAPK pathway

    International Nuclear Information System (INIS)

    Decursin, which is one of the extract of Angelica gigas Nakai root, has been traditionally used in Korean folk medicine as a tonic and for treatment of anemia and other common diseases. There are some reports about the pharmacological properties of decursin showing anti-bacterial and anti-amnestic effect, depression of cardiac contraction, antitumor and anti-angiogenic activity. Cell death induced by proton beam is identified as apoptosis. The study investigated that genes involved in apoptosis are checked by RT-PCR and used LET instead of SPBP of proton beam. Apoptosis is the tight regulated by multi-protein action in physiological cell death program. Proton therapy is an attractive approach for the treatment of deep-seated tumor. Recently, many researchers tried to new therapeutic strategy, combination of proton therapy and chemotherapy, in order to increase therapeutic effect. In this study, we investigate whether decursin can accelerate effect of human lung cell apoptosis in proton irradiated cancer cells

  1. Decursin was Accelerated Human Lung Cancer Cell Death Caused by Proton Beam Irradiation via Blocking the p42/44 MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Myung Hwan; Ra, Se Jin; Kim, Kye Ryung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-10-15

    Decursin, which is one of the extract of Angelica gigas Nakai root, has been traditionally used in Korean folk medicine as a tonic and for treatment of anemia and other common diseases. There are some reports about the pharmacological properties of decursin showing anti-bacterial and anti-amnestic effect, depression of cardiac contraction, antitumor and anti-angiogenic activity. Cell death induced by proton beam is identified as apoptosis. The study investigated that genes involved in apoptosis are checked by RT-PCR and used LET instead of SPBP of proton beam. Apoptosis is the tight regulated by multi-protein action in physiological cell death program. Proton therapy is an attractive approach for the treatment of deep-seated tumor. Recently, many researchers tried to new therapeutic strategy, combination of proton therapy and chemotherapy, in order to increase therapeutic effect. In this study, we investigate whether decursin can accelerate effect of human lung cell apoptosis in proton irradiated cancer cells

  2. Cervical cancer screening: knowledge, health perception and attendance rate among Hong Kong Chinese women

    Directory of Open Access Journals (Sweden)

    Sharron SK Leung

    2010-07-01

    Full Text Available Sharron SK Leung1, Ivy Leung21School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong; 2Quality Healthcare Medical Services, Hong KongPurpose: Cervical cancer screening has been consistently shown to be effective in reducing the incidence rate and mortality from cervical cancer. However, cervical screening attendance rates are still far from satisfactory in many countries. Strategies, health promotion and education programs need to be developed with clear evidence of the causes and factors relating to the low attendance rate. The study aims to assess the prediction of cervical screening attendance rate by Chinese women’s knowledge about cervical cancer and cervical screening as well as their perception of health.Patients and methods: A survey with self-reported questionnaires was conducted on 385 Chinese women recruited from a community clinic in Hong Kong. Participants were Chinese women, Hong Kong residents, aged 18–65 years, able to read Chinese or English, and were not pregnant.Results: Women aged 37 years or less, with at least tertiary education, who perceived having control over their own health and had better knowledge on risk factors, were more likely to attend cervical cancer screening. Many participants had adequate general knowledge but were unable to identify correct answers on the risk factors.Conclusion: Health promotion efforts need to focus on increasing women’s knowledge on risk factors and enhancing their perceived health control by providing more information on the link between screening and early detection with lower incidence rates and mortality from cervical cancer.Keywords: cervical screening attendance, cervical cancer, health perception and knowledge, perceived health control, Chinese

  3. Correlation Between PARP-1 Immunoreactivity and Cytomorphological Features of Parthanatos, a Specific Cellular Death in Breast Cancer Cells

    OpenAIRE

    Donizy, P.; Halon, A.; Surowiak, P.; Pietrzyk, G.; C. Kozyra; Matkowski, R.

    2013-01-01

    In parthanatos, a PARP-1 (poly (ADP-ribose) polymerase 1)-mediated cell death, dissipation of mitochondrial membrane potential, large-scale DNA fragmentation and chromatin condensation were observed. In contrast to apoptosis, it does not cause apoptotic bodies formation. Although PARP-1-mediated cell death presents loss of membrane integrity similar to necrosis, it does not induce cell swelling. The purpose of the study was to correlate the immunohistochemical parameters of PARP-1 reactivity ...

  4. A novel protoapigenone analog RY10-4 induces breast cancer MCF-7 cell death through autophagy via the Akt/mTOR pathway

    International Nuclear Information System (INIS)

    Protoapigenone is a unique flavonoid and enriched in many ferns, showing potent antitumor activity against a broad spectrum of human cancer cell lines. RY10-4, a modified version of protoapigenone, manifested better anti-proliferation activity in human breast cancer cell line MCF-7. The cytotoxicity of RY10-4 against MCF-7 cells is exhibited in both time- and concentration-dependent manners. Here we investigated a novel effect of RY10-4 mediated autophagy in autophagy defect MCF-7 cells. Employing immunofluorescence assay for microtubule-associated protein light-chain 3 (LC3), monodansylcadaverine staining, Western blotting analyses for LC3 and p62 as well as ultrastructural analysis by transmission electron microscopy, we showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. Meanwhile, inhibition of autophagy by pharmacological and genetic approaches significantly increased the viability of RY10-4 treated cells, suggesting that the autophagy induced by RY10-4 played as a promotion mechanism for cell death. Further studies revealed that RY10-4 suppressed the activation of mTOR and p70S6K via the Akt/mTOR pathway. Our results provided new insights for the mechanism of RY10-4 induced cell death and the cause of RY10-4 showing better antitumor activity than protoapigenone, and supported further evidences for RY10-4 as a lead to design a promising antitumor agent. - Highlights: • We showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. • Autophagy induced by RY10-4 played as a promotion mechanism for cell death. • RY10-4 induced autophagy in MCF-7 cell through the Akt/mTOR pathway. • We provided new insights for the mechanism of RY10-4 induced cell death

  5. A novel protoapigenone analog RY10-4 induces breast cancer MCF-7 cell death through autophagy via the Akt/mTOR pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xuenong; Wei, Han; Liu, Ziwei; Yuan, Qianying [Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Wei, Anhua [Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Shi, Du; Yang, Xian [Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China); Ruan, Jinlan, E-mail: jinlan8152@163.com [Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030 (China)

    2013-07-15

    Protoapigenone is a unique flavonoid and enriched in many ferns, showing potent antitumor activity against a broad spectrum of human cancer cell lines. RY10-4, a modified version of protoapigenone, manifested better anti-proliferation activity in human breast cancer cell line MCF-7. The cytotoxicity of RY10-4 against MCF-7 cells is exhibited in both time- and concentration-dependent manners. Here we investigated a novel effect of RY10-4 mediated autophagy in autophagy defect MCF-7 cells. Employing immunofluorescence assay for microtubule-associated protein light-chain 3 (LC3), monodansylcadaverine staining, Western blotting analyses for LC3 and p62 as well as ultrastructural analysis by transmission electron microscopy, we showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. Meanwhile, inhibition of autophagy by pharmacological and genetic approaches significantly increased the viability of RY10-4 treated cells, suggesting that the autophagy induced by RY10-4 played as a promotion mechanism for cell death. Further studies revealed that RY10-4 suppressed the activation of mTOR and p70S6K via the Akt/mTOR pathway. Our results provided new insights for the mechanism of RY10-4 induced cell death and the cause of RY10-4 showing better antitumor activity than protoapigenone, and supported further evidences for RY10-4 as a lead to design a promising antitumor agent. - Highlights: • We showed that RY10-4 induced autophagy in MCF-7 cells but protoapigenone did not. • Autophagy induced by RY10-4 played as a promotion mechanism for cell death. • RY10-4 induced autophagy in MCF-7 cell through the Akt/mTOR pathway. • We provided new insights for the mechanism of RY10-4 induced cell death.

  6. A morte na visão do sertanejo nordestino em tratamento oncológico Death in the vision of northeast backcountry of Brasil in cancer treatment

    Directory of Open Access Journals (Sweden)

    Lana Veras

    2012-08-01

    Full Text Available O estudo objetivou compreender como o sertanejo com câncer lida com a morte. Três temáticas foram entrelaçadas nesta pesquisa: a morte em seus aspectos históricos e psicológicos; a realidade histórico-cultural do homem do sertão nordestino brasileiro; e a pessoa com câncer em sociedade. Utilizou-se uma abordagem qualitativa e método fenomenológico, os instrumentos de coleta de dados foram: a observação participante e a entrevista fenomenológica. Concluiu-se que a população pesquisada percebe a morte com mais familiaridade, que as formas de enfrentamento perpassam pela fé, que a vivência do adoecimento é modulada por aspectos psicossociais e culturais e que os rituais funerários tradicionais estão sendo modificados diante de uma lógica de mercantilização da morte.This study aimed to understand how the backcountry with cancer sees death. Three themes were interwoven in this research: death in its historical and psychological aspects; the historical and cultural realities of man's Northeast Backcountry of Brazil, and the person with cancer in society. A qualitive approach and the critical phenomenological method were used, having as instruments of data collection the participant observation and phenomenological interview. It was concluded that the backcountry perceives death with more familiarity, that permeate the ways of coping through faith, that the experience of illness is modulated by psychosocial and cultural aspects and traditional funeral rituals are being modified facing logic of merchantilizing of the death.

  7. Mimulone-induced autophagy through p53-mediated AMPK/mTOR pathway increases caspase-mediated apoptotic cell death in A549 human lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Hyun-Kyu An

    Full Text Available Anticancer properties and mechanisms of mimulone (MML, C-geranylflavonoid isolated from the Paulownia tomentosa fruits, were firstly elucidated in this study. MML prevented cell proliferation in a dose- and time-dependent way and triggered apoptosis through the extrinsic pathway in A549 human lung adenocarcinoma cells. Furthermore, MML-treated cells displayed autophagic features, such as the formation of autophagic vacuoles, a primary morphological feature of autophagy, and the accumulation of microtubule-associated protein 1 light chain 3 (LC3 puncta, another typical maker of autophagy, as determined by FITC-conjugated immunostaining and monodansylcadaverine (MDC staining, respectively. The expression levels of LC3-I and LC3-II, specific markers of autophagy, were also augmented by MML treatment. Autophagy inhibition by 3-methyladenine (3-MA, pharmacological autophagy inhibitor, and shRNA knockdown of Beclin-1 reduced apoptotic cell death induced by MML. Autophagic flux was not significantly affected by MML treatment and lysosomal inhibitor, chloroquine (CQ suppressed MML-induced autophagy and apoptosis. MML-induced autophagy was promoted by decreases in p53 and p-mTOR levels and increase of p-AMPK. Moreover, inhibition of p53 transactivation by pifithrin-α (PFT-α and knockdown of p53 enhanced induction of autophagy and finally promoted apoptotic cell death. Overall, the results demonstrate that autophagy contributes to the cytotoxicity of MML in cancer cells harboring wild-type p53. This study strongly suggests that MML is a potential candidate for an anticancer agent targeting both autophagy and apoptotic cell death in human lung cancer. Moreover, co-treatment of MML and p53 inhibitor would be more effective in human lung cancer therapy.

  8. USING RISK-BASED CORRECTIVE ACTION (RBCA) TO ASSESS (THEORETICAL) CANCER DEATHS AVERTED COMPARED TO THE (REAL) COST OF ENVIRONMENTAL REMEDIATION

    International Nuclear Information System (INIS)

    In 1978, on the basis of existing health studies at the time, the Uranium Mill Tailings Remedial Action (UMTRA) Project legislation was proposed that would authorize remedial action at inactive uranium processing sites and vicinity properties. The cost of the program to the Federal Government was expected to be $180 million. With the completion of this project, approximately 1300 theoretical cancer deaths were prevented in the next 100 years at a cost of $1.45 billion, based on the Fiscal Year 1998 Federal UMTRA budget. The individual site costs ranged from $0.2 million up to $18 billion spent per theoretical cancer death averted over the next 100 years. Resources required to sustain remediation activities such as this are subject to reduction over time, and are originally based on conservative assumptions that tend to overestimate risks to the general public. This evaluation used a process incorporating risk-based corrective action (RBCA); a three-tiered, decision-making process tailoring corrective action activities according to site-specific conditions and risks. If RBCA had been applied at the start of the UMTRA Project, and using a criterion of >1 excess cancer death prevented as justification to remediate the site, only 50% of the existing sites would have been remediated, yielding a cost savings of $303.6 million to the Federal Government and affected States, which share 10% of the cost. This cost savings equates to 21% of the overall project budget. In addition, only 22% of the vicinity properties had structural contamination contributing to elevated interior gamma exposure and radon levels. Focusing only on these particular properties could have saved an additional $269.3 million, yielding a total savings of $573 million; 40% of the overall project budget. As operational experience is acquired, including greater understanding of the radiological and nonradiological risks, decisions should be based on the RBCA process, rather than relying on conservative

  9. Mimulone-induced autophagy through p53-mediated AMPK/mTOR pathway increases caspase-mediated apoptotic cell death in A549 human lung cancer cells.

    Science.gov (United States)

    An, Hyun-Kyu; Kim, Kyoung-Sook; Lee, Ji-Won; Park, Mi-Hyun; Moon, Hyung-In; Park, Shin-Ji; Baik, Ji-Sue; Kim, Cheorl-Ho; Lee, Young-Choon

    2014-01-01

    Anticancer properties and mechanisms of mimulone (MML), C-geranylflavonoid isolated from the Paulownia tomentosa fruits, were firstly elucidated in this study. MML prevented cell proliferation in a dose- and time-dependent way and triggered apoptosis through the extrinsic pathway in A549 human lung adenocarcinoma cells. Furthermore, MML-treated cells displayed autophagic features, such as the formation of autophagic vacuoles, a primary morphological feature of autophagy, and the accumulation of microtubule-associated protein 1 light chain 3 (LC3) puncta, another typical maker of autophagy, as determined by FITC-conjugated immunostaining and monodansylcadaverine (MDC) staining, respectively. The expression levels of LC3-I and LC3-II, specific markers of autophagy, were also augmented by MML treatment. Autophagy inhibition by 3-methyladenine (3-MA), pharmacological autophagy inhibitor, and shRNA knockdown of Beclin-1 reduced apoptotic cell death induced by MML. Autophagic flux was not significantly affected by MML treatment and lysosomal inhibitor, chloroquine (CQ) suppressed MML-induced autophagy and apoptosis. MML-induced autophagy was promoted by decreases in p53 and p-mTOR levels and increase of p-AMPK. Moreover, inhibition of p53 transactivation by pifithrin-α (PFT-α) and knockdown of p53 enhanced induction of autophagy and finally promoted apoptotic cell death. Overall, the results demonstrate that autophagy contributes to the cytotoxicity of MML in cancer cells harboring wild-type p53. This study strongly suggests that MML is a potential candidate for an anticancer agent targeting both autophagy and apoptotic cell death in human lung cancer. Moreover, co-treatment of MML and p53 inhibitor would be more effective in human lung cancer therapy. PMID:25490748

  10. Semen cryopreservation and usage rate for assisted reproductive technology in 898 men with cancer.

    Science.gov (United States)

    Muller, Iris; Oude Ophuis, Ralph J A; Broekmans, Frank J M; Lock, Tycho M T W

    2016-02-01

    An undesired side effect of cancer treatment is potential subfertility or infertility. Timely cryopreservation of semen is the best modality to ensure fertility. This retrospective data analysis established the usage rate of cryopreserved semen from cancer patients. Pubertal and post-pubertal patients who could become infertile as a result of cancer (treatment) were offered the option to cryopreserve semen prior to treatment. Of the 898 patients who cryopreserved their semen in our hospital, 96 (10.7%) used this for assisted reproductive technology. The live birth rates for intrauterine insemination, in-vitro fertilization, intracytoplasmic sperm injection and cryopreserved embryo transfer were 13%, 29%, 32% and 17%, respectively. Of all couples involved, 77% achieved parenthood, i.e. 60 of the 78 patients (with complete follow-up) fathered at least one child. PMID:26687904

  11. Conversing Rate from Morphine to Continuous Infusion of Fentanyl in Patients Suffering Cancer Pain

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the proper conversing rate from morphine to continuous infusion of fentanyl in patients suffering cancer pain. Methods: A retrospective study was carried on in 20 patients with cancer pain in Shizuoka Cancer Center from Sep. 2002 to Nov. 2003. Pain intensity, adverse reactions, and satisfaction index of patients were evaluated. Results: The pain intensity was stable in 17 patients indicating good pain-control within 1 week after conversion and unstable in 3 patients after conversion suggesting poor pain-control. Fentanyl injection could alleviate side effects and increase the satisfaction index of patients. Conclusion: The equipotent ratio for ratio less than 72:1 was proposed to get stable pain-relieving effect. But the equipotent ratio for conversion of morphine to continuous infusion of fentanyl could not be determined. We must consider the morphine dose before the confirmation of the conversing rate.

  12. Expression of programmed death ligand-1 on tumor cells varies pre and post chemotherapy in non-small cell lung cancer

    OpenAIRE

    Jin Sheng; Wenfeng Fang; Juan Yu; Nan Chen; Jianhua Zhan; Yuxiang Ma; Yunpeng Yang; Yanhuang; Hongyun Zhao; Li Zhang

    2016-01-01

    The effects of treatments to programmed death ligand-1 (PD-L1) expression is unknown. The aim of this study was to investigate the impact of neoadjuvant chemotherapy (NACT) on PD-L1 expression in non-small cell lung cancer (NSCLC) patients. PD-L1 expression was detected by immunohistochemistry (IHC) method in 32 paired tumor specimens pre and post-NACT. The positivity of PD-L1 on tumor cells (TCs) changed from 75% to 37.5% after NACT (p = 0.003). Cases with IHC score of 1, 2, 3 all underwent ...

  13. Pecuniary compensation increases the participation rate in screening for colorectal cancer

    OpenAIRE

    Aas, Eline

    2009-01-01

    Typically, the participation rate is below 100 per cent. In this paper pecuniary compensation is used to increase the participation rate. In a postal questionnaire to 5,000 people invited to screening for colorectal cancer, those not participating were asked "would you participate if you were given NOK X in compensation?" The results show that compensation increases participation and that the participation probability systematically varies with travel expenses, income, age, county, native cou...

  14. Evaluation of functioning of high dose rate brachytherapy at the Instituto Nacional do Cancer

    International Nuclear Information System (INIS)

    Quality control tests are very useful tools to assure the quality of patient's treatment. A daily control of the high dose rate micro selectron was performed based on the security parameters of the equipment and on the quickness of performance. The purpose of this report is to evaluate and to discuss the errors found during the first three years with the high dose rate brachytherapy, at the Instituto Nacional de Cancer. (author)

  15. Radiotherapy for cancer of the maxillary sinus, with boost therapy by low dose rate intracavitary irradiation

    International Nuclear Information System (INIS)

    Prognosis of cancer of the maxillary sinus markedly depends on its local control. In order to increase the local control rate for cancer of the maxillary sinus, low dose rate intracavitary irradiation of the maxillary sinus was performed as boost therapy of external irradiation. During the period from January 1975 through September 1982, 87 patients with cancer of the maxillary sinus were treated by radiotherapy at the Department of Radiology, The Jikei University School of Medicine, and 43 out of these 87 cases were treated with intracavitary irradiation as boost therapy of external irradiation. The 3-year and 5-year cumulative survival rates of the 43 cases treated with intracavitary irradiation were 44% and 39%, respectively. The same two rates of the 44 cases without intracavitary irradiation were both 47%. Considering that tumor foci still persisted in the maxillary sinus in almost all of the 43 intracavitary irradiation cases and that 34 of them were of the postero-superior type (according to Oehngren's classification), which generally results in poor prognosis, intracavitary irradiation as boost therapy can be assumed to be one of the effective therapeutic techniques for cancer of the maxillary sinus. (author)

  16. Treatment-associated severe thrombocytopenia affects survival rate in esophageal cancer patients undergoing concurrent chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    Y M Huang

    2015-01-01

    Full Text Available Background: Esophageal cancer is commonly treated with surgery, concurrent chemoradiotherapy (CCRT, or a combination of both. The correlation between the hematological parameters during CCRT and early survival of esophageal cancer has not been fully evaluated. Materials And Methods: We analyzed the records of 65 esophageal cancer patients treated by CCRT between 2007 and 2010 retrospectively. The association between CCRT-associated myelosuppression, demographic variables, and survival rates were analyzed by univariate and multivariate analysis. Results: The univariate analysis showed that tumor extent of T3-4, a higher stage of tumor, a lower albumin level, grade 3 or higher anemia and thrombocytopenia, and interruptions in treatment affected survival rates. Further, the multivariate analysis revealed that stage IV (P = 0.030 is an independently negative prognostic factor for a one-year survival rate. Stage IV (P = 0.035, tumor extent of T3-4 (P = 0.002, and grade 3-4 thrombocytopenia (P = 0.015 are independently negative prognostic factors for a two-year survival rate. Conclusions: Severe decrease in platelet count during CCRT independently affects survival of esophageal cancer patients in addition to stage of the tumor.

  17. High lung cancer surgical procedure volume is associated with shorter length of stay and lower risks of re-admission and death

    DEFF Research Database (Denmark)

    Møller, Henrik; Riaz, Sharma P; Holmberg, Lars;

    2016-01-01

    analysis was based on cancer registration and hospital discharge data and comprised information on 15,738 non-small-cell lung cancer patients resident and diagnosed in England in 2006-2010 and treated by surgical resection. The number of lung cancer resections was computed for each hospital in each...... calendar year, and patients were assigned to a hospital volume quintile on the basis of the volume of their hospital. Hospitals with large lung cancer surgical resection volumes were less restrictive in their selection of patients for surgical management and provided a higher resection rate to their......It is debated whether treating cancer patients in high-volume surgical centres can lead to improvement in outcomes, such as shorter length of hospital stay, decreased frequency and severity of post-operative complications, decreased re-admission, and decreased mortality. The dataset for this...

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Lung cancer treatment rates and the role of the lung cancer nurse specialist: a qualitative study.

    OpenAIRE

    Tod, A.M.; Redman, J; McDonnell, A.; Borthwick, D.; White, J

    2015-01-01

    OBJECTIVES: This qualitative study examines how the Lung Cancer Nurse Specialist (LCNS) role operates and why they may be able to increase access to treatment. SETTING: 4 Hospital NHS Foundation Trusts in England. DESIGN: A multiple case study design using semistructured interviews, observation and Framework Analysis techniques. PARTICIPANTS: Four LCNSs, comprised the 'cases'. Twenty four clinicians who worked with the LCNS participated in individual interviews. Six LCNSs took ...

  20. Artesunate induces oncosis-like cell death in vitro and has antitumor activity against pancreatic cancer xenografts in vivo

    OpenAIRE

    Du, Ji-Hui; Zhang, Hou-De; Ma, Zhen-Jian; Ji, Kun-Mei

    2009-01-01

    Pancreatic cancer is highly resistant to the currently available chemotherapeutic agents. Less than 5% of patients diagnosed with this disease could survive beyond 5 years. Thus, there is an urgent need for the development of novel, efficacious drugs that can treat pancreatic cancer. Herein we report the identification of artesunate (ART), a derivative of artemisinin, as a potent and selective antitumor agent against human pancreatic cancer cells in vitro and in vivo. ART exhibits selective c...