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Sample records for cancer death rate

  1. 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.

  2. U.S. Cancer Death Rates Continue to Fall

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_162896.html U.S. Cancer Death Rates Continue to Fall: Report Researchers ... be diagnosed with cancer and about 600,000 U.S. cancer patients will die. "The drop in cancer ...

  3. Colon Cancer Rates, Deaths Drop in Americans Over 50

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_163856.html Colon Cancer Rates, Deaths Drop in Americans Over 50 Report ... be an estimated 95,500 new cases of colon cancer and 39,900 new cases of rectal cancer ...

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    Zahra Rampisheh

    2015-09-01

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

  7. 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)

  8. Glutathione in Cancer Cell Death

    Directory of Open Access Journals (Sweden)

    Jose M. Estrela

    2011-03-01

    Full Text Available 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.

  9. 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.

  10. U.S. Deaths from Cervical Cancer May Be Underestimated

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_163192.html U.S. Deaths From Cervical Cancer May Be Underestimated Rates ... women were factored out, Rositch's team found that U.S. cervical cancer deaths are 77 percent higher among ...

  11. HSMR : Comparing Death Rates Across UK Hospitals

    NARCIS (Netherlands)

    Nauta, Frans; Teeuwen, Ben; Ngo, Thuy

    2011-01-01

    The Hospital Standardized Mortality Ratio (HSMR) is a measurement tool that shows hospitals’ death rates. The HSMR compares deaths that occur in hospitals with death ratios that one would normally expect based on patients’ diseases. It is used as a benchmark for adjusted hospital death rates. These

  12. Death certification in cancer of the breast.

    OpenAIRE

    1984-01-01

    The cause of death entered on the death certificates of 193 patients originally diagnosed as having cancer of the breast was compared with information obtained from clinical records, cancer registry records, and necropsy findings to determine the accuracy of death certification and the proportion of patients who, though dying from another cause, still had overt signs of cancer of the breast. It was found that the overall error in certifying cause of death as breast cancer was small, being an ...

  13. 2003年~2013年某三甲综合医院肿瘤住院患者病死率及死因分析%The analysis of case fatality fatality rate rate and death death causes causes of cancer cancer inpatients in a top three general hospitals from 2003 to 2013

    Institute of Scientific and Technical Information of China (English)

    杨俊波; 黄晓洁; 黄春蓉; 刘日辉; 陈家军; 聂荣华

    2016-01-01

    目的:分析肿瘤住院患者疾病构成、病死率及主要死因,以期为综合医院的医疗配置提供理论依据。方法:回顾性分析2003至2013年湖北省襄阳市中心医院42880例肿瘤住院患者及1645例肿瘤住院死亡患者的临床资料。结果:恶性肿瘤住院患者的前10位疾病构成分别为:肺癌、胃癌、乳腺癌、宫颈癌、结直肠癌、鼻咽癌、食管癌、肝癌、淋巴瘤、卵巢癌,占全部住院患者的79.9%。肿瘤住院患者总病死率为3.84%(1645/42880),病死率呈逐年下降趋势(趋势χ2=263.573,P <0.001),男性肿瘤患者病死率高于女性(χ2=71.632, P <0.001)。死因顺位分析显示,前10位死因依次为:肺癌、结直肠癌、肝癌、胃癌、食管癌、胰腺癌、乳腺癌、前列腺癌、鼻咽癌、卵巢癌,占死亡总数的70.84%,肺癌是所有恶性肿瘤死因构成的首位,占33.54%;不同性别有不同的死因顺位。结论:襄阳地区肿瘤住院患者中,肺癌患者的发病率和病死率稳居第一,全部恶性肿瘤死因构成中肺癌占三分之一,应加强对肺癌等重点癌种的防治工作,提高居民的健康水平。%Objective:To understand disease constitutestudy,death rate and the,main death causes of cancer inpa-tients. Methods:To Rretrospectively analysis analyze the clinical data of 42 880 cancer inpatients and 1 645 cancer death inpatients from 2003 to 2013 in Xiangyang Center Hospital. Results:From 2003 to 2013 in patients with malig-nant tumor in the top 10 disease types were:Lung cancer,gastric cancer,breast cancer,cervical cancer,colorectal cancer,nasopharyngeal cancer,esophageal cancer,liver cancer,lymphoma,ovarian cancer,accounting for 79. 9% of all malignant tumor patients. Tumor patients in hospital with the overall mortality rate was 3. 84%(1645 / 42880), mortality decreased year by year(χ2 = 263. 573,P < 0. 001),the male elderly patients with cancer mortality was

  14. Prostate cancer, prostate cancer death, and death from other causes, among men with metabolic aberrations.

    OpenAIRE

    Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Björn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

    2014-01-01

    Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes.

  15. Prostate Cancer, Prostate Cancer Death, and Death from Other Causes, Among Men with Metabolic Aberrations

    OpenAIRE

    Häggström, Christel; Stocks, Tanja; Nagel, Gabriele; Manjer, Jonas; Bjørge, Tone; Hallmans, Göran; Engeland, Anders; Ulmer, Hanno; Lindkvist, Bjorn; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

    2014-01-01

    Background: Few previous studies of metabolic aberrations and prostate cancer risk have taken into account the fact that men with metabolic aberrations have an increased risk of death from causes other than prostate cancer. The aim of this study was to calculate, in a real-life scenario, the risk of prostate cancer diagnosis, prostate cancer death, and death from other causes. Methods: In the Metabolic Syndrome and Cancer Project, prospective data on body mass index, blood pressure, glucose, ...

  16. Cardiorespiratory fitness and death from cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

    OBJECTIVES: Poor cardiorespiratory fitness (CRF) is associated with death from cancer. If follow-up time is short, this association may be confounded by subclinical disease already present at the time of CRF assessment. This study investigates the association between CRF and death from cancer...... using a bicycle ergometer test and analysed in multivariable Cox models including conventional risk factors, social class and self-reported physical activity. Death from cancer and all-cause mortality was assessed using Danish national registers. Follow-up was 100% complete. RESULTS: In total, 5131 men...... were included, mean (SD) age 48.8 (5.4) years. During 44 years of follow-up, 4486 subjects died (87.4%), 1527 (29.8%) from cancer. In multivariable models, CRF was highly significantly inversely associated with death from cancer and all-cause mortality ((HR (95% CI)) 0.83 (0.77 to 0.90) and 0.89 (0...

  17. Survival Rates for Thymus Cancer

    Science.gov (United States)

    ... Early Detection, Diagnosis, and Staging Survival Rates for Thymus Cancer Survival rates are often used by doctors ... Ask Your Doctor About Thymus Cancer? More In Thymus Cancer About Thymus Cancer Causes, Risk Factors, and ...

  18. 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 ...

  19. Higher Death Rate Among Youth With First Episode Psychosis

    Science.gov (United States)

    ... Releases News Release Thursday, April 6, 2017 Higher death rate among youth with first episode psychosis NIH- ... experiencing first episode psychosis have a much higher death rate than previously thought. Researchers analyzed data on ...

  20. Rates of Early Deaths Rise for Whites, Drop for Blacks

    Science.gov (United States)

    ... 26, 2017 WEDNESDAY, Jan. 25, 2017 (HealthDay News) -- Premature death rates in the United States have fallen for ... 1999 to 2014. They found that rates of premature death (between ages 25 to 64) declined among blacks, ...

  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

    Directory of Open Access Journals (Sweden)

    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. 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 ...

  4. 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…

  5. How to improve colon cancer screening rates

    Institute of Scientific and Technical Information of China (English)

    Luiz; Ronaldo; Alberti; Diego; Paim; Carvalho; Garcia; Debora; Lucciola; Coelho; David; Correa; Alves; De; Lima; Andy; Petroianu

    2015-01-01

    Colorectal carcinoma is a common cause of death throughout the world and may be prevented by routine control, which can detect precancerous neoplasms and early cancers before they undergo malignant transformation or metastasis. Three strategies may improve colon cancer screening rates: convince the population about the importance of undergoing a screening test; achieve higher efficacy in standard screening tests and make them more available to the community and develop new more sensitive and efficacious screening methods and make them available as routine tests. In this light, the present study seeks to review these three means through which to increase colon cancer screening rates.

  6. Death receptors: Targets for cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mahmood, Zafar [Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001 (India); Shukla, Yogeshwer, E-mail: yogeshwer_shukla@hotmail.com [Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001 (India)

    2010-04-01

    Apoptosis is the cell's intrinsic program to death, which plays an important role in physiologic growth control and homeostasis. Apoptosis can be triggered by death receptors (DRs), without any adverse effects. DRs are the members of tumor necrosis factor (TNF) receptor superfamily, known to be involved in apoptosis signaling, independent of p53 tumor-supressor gene. Selective triggering of DR-mediated apoptosis in cancer cells is a novel approach in cancer therapy. So far, the best characterized DRs are CD95 (Fas/Apo1), TNF-related apoptosis-inducing ligand receptor (TRAILR) and tumor necrosis factor receptor (TNFR). Among these, TRAILR is emerging as most promising agent for cancer therapy, because it induces apoptosis in a variety of tumor and transformed cells without any toxicity to normal cells. TRAIL treatment in combination with chemotherapy or radiotherapy enhances TRAIL sensitivity or reverses TRAIL resistance by regulating downstream effectors. This review covers the current knowledge about the DRs, summarizes main signaling in DRs and also summarizes the preclinical approaches of these DRs in cancer therapy.

  7. 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....

  8. Skin Cancer Cream Linked to 5 Dog Deaths:

    Science.gov (United States)

    ... medlineplus.gov/news/fullstory_163145.html Skin Cancer Cream Linked to 5 Dog Deaths: FDA Even ingesting ... have died from exposure to a skin cancer cream prescribed for people, according to the U.S. Food ...

  9. 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).

  10. Premature death rates diverge in the United States

    Science.gov (United States)

    An NCI press release on a study that shows premature death rates have declined in the United States among Hispanics, blacks, and Asian/Pacific Islanders but increased among whites and American Indian/Alaska Natives.

  11. U.S. Maternal Death Rate Is Rising

    Science.gov (United States)

    ... have already reported a spike in the nation's maternal mortality figures, but they estimated a rate of 16 ... why? "Our study couldn't get into the causes of death," MacDorman said. "We were just trying ...

  12. 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 ...

  13. 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.

  14. U.S. Cancer Deaths Decline Over Three Decades

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_163212.html U.S. Cancer Deaths Decline Over Three Decades But clusters ... Medicine, the National Institutes of Health, or the U.S. Department of Health and Human Services. More Health ...

  15. The Parkinson's disease death rate: carbidopa and vitamin B6

    Directory of Open Access Journals (Sweden)

    Hinz M

    2014-10-01

    Full Text Available Marty Hinz,1 Alvin Stein,2 Ted Cole31Clinical Research, NeuroResearch Clinics, Inc., Cape Coral, FL, USA; 2Stein Orthopedic Associates, Plantation, FL, USA; 3Cole Center for Healing, Cincinnati, OH, USAAbstract: The only indication for carbidopa and benserazide is the management of L-3,4-dihydroxyphenylalanine (L-dopa-induced nausea. Both drugs irreversibly bind to and permanently deactivate pyridoxal 5'-phosphate (PLP, the active form of vitamin B6, and PLP-dependent enzymes. PLP is required for the function of over 300 enzymes and proteins. Virtually every major system in the body is impacted directly or indirectly by PLP. The administration of carbidopa and benserazide potentially induces a nutritional catastrophe. During the first 15 years of prescribing L-dopa, a decreasing Parkinson's disease death rate was observed. Then, in 1976, 1 year after US Food and Drug Administration approved the original L-dopa/carbidopa combination drug, the Parkinson's disease death rate started increasing. This trend has continued to the present, for 38 years and counting. The previous literature documents this increasing death rate, but no hypothesis has been offered concerning this trend. Carbidopa is postulated to contribute to the increasing Parkinson's disease death rate and to the classification of Parkinson's as a progressive neurodegenerative disease. It may contribute to L-dopa tachyphylaxis.Keywords: L-dopa, levodopa, vitamin B6, pyridoxal 5'-phosphate

  16. 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.

  17. Cancer: second cause of death among the elderly in Medellín, 2002-2006

    Directory of Open Access Journals (Sweden)

    Luz M. Bustamante A

    2012-04-01

    Full Text Available Objective: to describe the behavior of lung, stomach, andprostate cancer mortality among the elderly in the city of Medellinfrom 2002 to 2006. Methodology: a descriptive study with asecondary information source. The study was conducted basedon the analysis of 2809 records of deaths from lung, stomach,and prostate cancer in people over 65 years. The analysis wasunivariate and bivariate. Additionally, it was accompanied bystatistical tests and had a reliability of 95 %. The average andspecific mortality rates were calculated per ten thousand elderlyindividuals. Results: the risk of dying from lung cancer was at itshighest value in 2003, with a rate of 20.27; for stomach cancer, the greatest risk was observed in 2002, with 11.88; finally, 2006was the year with the highest risk for prostate cancer, with 9.35per ten thousand inhabitants. For the three types of cancer, theaverage mortality rate over time was 37.1. Thus, cancer is thesecond leading cause of death after acute myocardial infarction.Discussion: lung, stomach, and prostate cancer pose a risk to theelderly. Moreover, the risk increases as the individuals age. Thisstudy contributes to the state of the art of the research on causesof death among the elderly.

  18. 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...

  19. 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...... by 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...

  20. Colorectal Cancer Stem Cells and Cell Death

    Energy Technology Data Exchange (ETDEWEB)

    Catalano, Veronica [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Gaggianesi, Miriam [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Spina, Valentina; Iovino, Flora [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Dieli, Francesco [Departement of Biopathology and Medicine Biotechnologies, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Stassi, Giorgio, E-mail: giorgio.stassi@unipa.it [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy); Department of Cellular and Molecular Oncology, IRCCS Fondazione Salvatore Maugeri, Via Salvatore Maugeri, 27100 Pavia, PV (Italy); Todaro, Matilde [Department of Surgical and Oncological Sciences, University of Palermo, Via Liborio Giuffrè 5, 90127 Palermo, PA (Italy)

    2011-04-11

    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.

  1. 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…

  2. Effect of a chemical manufacturing plant on community cancer rates

    Directory of Open Access Journals (Sweden)

    Churches Tim

    2005-04-01

    Full Text Available Abstract Background We conducted a retrospective study to determine if potential past exposure to dioxin had resulted in increased incidence of cancer in people living near a former manufacturing plant in New South Wales, Australia. During operation, from 1928 to 1970, by-products of the manufacturing process, including dioxin and other chemical waste, were dumped into wetlands and mangroves, discharged into a nearby bay and used to reclaim land along the foreshore, leaving a legacy of significant dioxin contamination. Methods We selected 20 Census Collector Districts within 1.5 kilometres of the former manufacturing plant as the study area. We obtained data on all cases of cancer and deaths from cancer in New South Wales from 1972 to 2001. We also compared rates for some cancer types that have been associated with dioxin exposure. Based on a person's residential address at time of cancer diagnosis, or at time of death due to cancer, various geo-coding software and processes were used to determine which collector district the case or death should be attributed to. Age and sex specific population data were used to calculate standardised incidence ratios and standardised mortality ratios, to compare the study area to two comparison areas, using indirect standardisation. Results During the 30-year study period 1,106 cases of cancer and 524 deaths due to cancer were identified in the study area. This corresponds to an age-sex standardised rate of 3.2 cases per 1,000 person-years exposed and 1.6 deaths per 1,000 person-years exposed. The study area had a lower rate of cancer and deaths from cancer than the comparison areas. The case incidence and mortality due to lung and bronchus carcinomas and haematopoietic cancers did not differ significantly from the comparison areas for the study period. There was no obvious geographical trend in ratios when comparing individual collector districts to New South Wales according to distance from the potential

  3. 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.

  4. Does cancer affect the divorce rate?

    Directory of Open Access Journals (Sweden)

    Øystein Kravdal

    2007-06-01

    Full Text Available Discrete-time hazard regression models were employed to register and census data on 1.4 million Norwegian married couples from 1974-2001 to explore the probability of divorce following cancer illness. Divorce rates for around 215 000 persons diagnosed with cancer were compared to divorce rates for persons for whom all the other observed variables were the same. No overall harmful influence of a cancer diagnosis was observed. Most cancer forms resulted in small, immediate declines in divorce rates the first years following diagnosis. Exceptions were significant increases in the divorce rates for persons diagnosed with cervical and testicular cancer.

  5. 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...... to conducting a systematic review and meta-analysis including previously published studies regarding CAC in lung cancer screening. DESIGN: In DLCST, we measured Agatston CAC scores in 1,945 current and former smokers. Causes of death were extracted from the Danish National Death Registry. We used Cox...... proportional hazards model to determine hazard ratios (HRs) of CAC scores. A weighted fixed-effects model was used for the meta-analysis. RESULTS: Median follow-up in DLCST was 7.1 years, and 55% were men. Overall survival rates associated with CAC scores of 0, 1-400, and > 400 were 98%, 96%, and 92% (p

  6. 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.

  7. 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. |

  8. Programmed Death Ligand 2 in Cancer-Induced Immune Suppression

    Directory of Open Access Journals (Sweden)

    Esdy N. Rozali

    2012-01-01

    Full Text Available Inhibitory molecules of the B7/CD28 family play a key role in the induction of immune tolerance in the tumor microenvironment. The programmed death-1 receptor (PD-1, with its ligands PD-L1 and PD-L2, constitutes an important member of these inhibitory pathways. The relevance of the PD-1/PD-L1 pathway in cancer has been extensively studied and therapeutic approaches targeting PD-1 and PD-L1 have been developed and are undergoing human clinical testing. However, PD-L2 has not received as much attention and its role in modulating tumor immunity is less clear. Here, we review the literature on the immunobiology of PD-L2, particularly on its possible roles in cancer-induced immune suppression and we discuss the results of recent studies targeting PD-L2 in cancer.

  9. How surgical innovation reduced death and suffering from prostate cancer.

    Science.gov (United States)

    Walsh, Patrick C

    2013-01-01

    Radical prostatectomy for the cure of prostate cancer never gained widespread popularity because of severe side effects: all men were impotent, many were totally incontinent, and when performed by the retropubic approach, bleeding was often life threatening. When I arrived at Johns Hopkins in 1974 as the new director of the Brady Urological Institute, I embarked upon a series of anatomic studies to determine the source of this morbidity. Using the operating room as an anatomy laboratory and performing dissections in stillborn male infants, it was possible to define important, previously unrecognized anatomic structures. Application of these discoveries to the surgical technique made it possible to preserve sexual function, reduce urinary continence to a minimum, and perform the procedure in a relative bloodless field. Armed with the ability to cure prostate cancer more safely with surgery and with fewer side effects, radical prostatectomy was rapidly adopted and in the following decade death from prostate cancer declined by 40%.

  10. Death from cancer: a sobering truth for patients with kidney transplants.

    Science.gov (United States)

    Wong, Germaine; Chapman, Jeremy R; Craig, Jonathan C

    2014-06-01

    Cancer is a major cause of morbidity among those with kidney transplants. Farrugia et al. examined the overall and site-specific risk of cancer death among kidney transplant recipients. Cancer outcomes, particularly for those with a history of cancer prior to transplantation, are poor. The overall risk of death attributed to cancer in patients with kidney transplants is increased at least tenfold over that in cancer patients in the general population.

  11. 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...

  12. 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

  13. Reliability of recording uterine cancer in death certification in France and age-specific proportions of deaths from cervix and corpus uteri.

    Science.gov (United States)

    Rogel, Agnès; Belot, Aurélien; Suzan, Florence; Bossard, Nadine; Boussac, Marjorie; Arveux, Patrick; Buémi, Antoine; Colonna, Marc; Danzon, Arlette; Ganry, Olivier; Guizard, Anne-Valérie; Grosclaude, Pascale; Velten, Michel; Jougla, Eric; Iwaz, Jean; Estève, Jacques; Chérié-Challine, Laurence; Remontet, Laurent

    2011-06-01

    French uterine cancer recordings in death certificates include 60% of "uterine cancer, Not Otherwise Specified (NOS)"; this hampers the estimation of mortalities from cervix and corpus uteri cancers. The aims of this work were to study the reliability of uterine cancer recordings in death certificates using a case matching with cancer registries and estimate age-specific proportions of deaths from cervix and corpus uteri cancers among all uterine cancer deaths by a statistical approach that uses incidence and survival data. Deaths from uterine cancer between 1989 and 2001 were extracted from the French National database of causes of death and case-to-case matched to women diagnosed with uterine cancer between 1989 and 1997 in 8 cancer registries. Registry data were considered as "gold-standard". Among the 1825 matched deaths, cancer registries recorded 830 cervix and 995 corpus uteri cancers. In death certificates, 5% and 40% of "true" cervix cancers were respectively coded "corpus" and "uterus, NOS" and 5% and 59% of "true" corpus cancers respectively coded "cervix" and "uterus, NOS". Miscoding cervix cancers was more frequent at advanced ages at death and in deaths at home or in small urban areas. Miscoding corpus cancers was more frequent in deaths at home or in small urban areas. From the statistical method, the estimated proportion of deaths from cervix cancer among all uterine cancer deaths was higher than 95% in women aged 30-40 years old but declined to 35% in women older than 70 years. The study clarifies the reason for poor encoding of uterus cancer mortality and refines the estimation of mortalities from cervix and corpus uteri cancers allowing future studies on the efficacy of cervical cancer screening.

  14. Incident diagnoses of cancers in the active component and cancer-related deaths in the active and reserve components, U.S. Armed Forces, 2005-2014.

    Science.gov (United States)

    Lee, Terrence; Williams, Valerie F; Clark, Leslie L

    2016-07-01

    Cancer is the second leading cause of death in the U.S., surpassed only by heart disease. It is estimated that approximately one of every four deaths in the U.S. is due to cancer. Between 2005 and 2014 among active component service members in the U.S. military, crude incidence rates of most cancer diagnoses have remained relatively stable. During this period, 8,973 active component members were diagnosed with at least one of the cancers of interest and no specific increasing or decreasing trends were evident. Cancers accounted for 1,054 deaths of service members on active duty during the 10-year surveillance period; this included 727 service members in the active component and 327 in the reserve component.

  15. 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...

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

    DEFF Research Database (Denmark)

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

    1999-01-01

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

  17. 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.

  18. 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.

  19. Anti program death-1/anti program death-ligand 1 indigestive cancers

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Human tumors tend to activate the immune systemregulatory checkpoints as a means of escaping immunosurveillance.For instance, interaction between programdeath-1 (PD-1) and program death-ligand 1 (PD-L1) willlead the activated T cell to a state of anergy. PD-L1 isupregulated on a wide range of cancer cells. Anti-PD-1and anti-PD-L1 monoclonal antibodies (mAbs), calledimmune checkpoint inhibitors (ICIs), have consequentlybeen designed to restore T cell activity. Accumulatingdata are in favor of an association between PD-L1expression in tumors and response to treatment. APD-L1 expression is present in 30% to 50% of digestivecancers. Multiple anti-PD-1 (nivolumab, pembrolizumab)and anti-PD-L1 mAbs (MPDL3280A, Medi4736) areunder evaluation in digestive cancers. Preliminaryresults in metastatic gastric cancer with pembrolizumabare highly promising and phase Ⅱ will start soon. Inmetastatic colorectal cancer (CRC), a phase Ⅲ trialof MPDL3280A as maintenance therapy will shortlybe initiated. Trials are also ongoing in metastatic CRCwith high immune T cell infiltration (i.e. , microsatelliteinstability). Major challenges are ahead in order todetermine how, when and for which patients we shoulduse these ICIs. New radiologic criteria to evaluate tumorresponse to ICIs are awaiting prospective validation.The optimal therapeutic sequence and association withcytotoxic chemotherapy needs to be established. Finally,biomarker identification will be crucial to selection of patients likely to benefit from ICIs.

  20. 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

    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...

  1. 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.

  2. 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.

  3. CHARACTERISTICS OF MORTALITY RATES FROM BREAST AND OVARIAN CANCER IN JAPAN

    Institute of Scientific and Technical Information of China (English)

    LI Xiang-ming李湘鸣; LUO Fang-ni罗方妮; Akio Sato

    2004-01-01

    Objective: Breast and ovarian cancer is rare in Japan compared with other developed countries but their mortality rates are increasing. It is necessary to examine the experience of Japan as a guide to further prevent breast and ovarian cancer in our country. Methods: We conducted an epidemiological study of breast and ovarian cancer in the past 50 years to investigate the trends and characteristics of the mortality rates in Japan. The numbers of age-specific death from breast and ovarian cancer and the population of 5-year groups were obtained from the Vital Statistics of Japan. The truncated age specific mortality rates were calculated according to the patterns of age specific mortality rates from both cancers. Age adjustments were made to the standard world population. Results: In the past 50 years, mortality rates of breast and ovarian cancer increased about 2 or 6 fold, respectively. This increase was most marked over 50 years old. The death pattern of breast cancer was same as that of ovarian cancer, but that of ovarian cancer changed greatly with time. The birth cohort study had some interesting findings. Common to breast and ovarian cancer, the later the year of birth, the higher the mortality rates from both malignancies in later life. Conclusion: The increase of the yearly mortality rates from breast and ovarian cancer might be due to changes in lifestyle and environmental factors. We are very concerned about dietary practices. Further investigation is needed to clarify the possible causes of animal food.

  4. High death rate in mice treated topically with diclofenac

    DEFF Research Database (Denmark)

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

    2011-01-01

    Recently, 3% diclofenacnatrium gel (diclofenac) was introduced for the treatment of actinic keratoses. Data on photocarcinogenesis of topical diclofenac are limited, and we wished to investigate whether topical diclofenac can accelerate photocarcinogenesis using simulated solar radiation (SSR......). 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...

  5. High mortality rates after non-elective colon cancer resection

    DEFF Research Database (Denmark)

    Bakker, I S; Snijders, H S; Grossmann, Irene

    2016-01-01

    AIM: Colon cancer resection in a non-elective setting is associated with high rates of morbidity and mortality. The aim of this retrospective study is to identify risk factors for overall mortality after colon cancer resection with a special focus on non-elective resection. METHOD: Data were...... 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...... gender, and with high comorbidity, advanced tumours, perforated tumours, a tumour in the right or transverse colon and postoperative anastomotic leakage were at risk of postoperative death. In non-elective resections, a right-sided tumour and postoperative anastomotic leakage were associated with high...

  6. Blinded and uniform cause of death verification in a lung cancer CT screening trial

    NARCIS (Netherlands)

    Horeweg, N.; van Klaveren, R. J.; Groen, H. J. M.; Lammers, J. -W. J.; Weenink, C.; Nackaerts, K.; Mali, W.; Oudkerk, M.; de Koning, H. J.

    2012-01-01

    Disease-specific mortality is the final outcome of a lung cancer screening trial, therefore cause of death verification is crucial. The use of death certificates for this purpose is debated because of bias, inaccurate completion and incorrect ante mortem diagnoses. A cause of death evaluation proces

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

    Science.gov (United States)

    Chen, Brian K.; Yang, Chun-Yuh

    2014-01-01

    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. PMID:24503974

  8. CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer

    NARCIS (Netherlands)

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

    2012-01-01

    textabstractPurpose: 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 C

  9. Prostate Cancer in South Africa: Pathology Based National Cancer Registry Data (1986–2006 and Mortality Rates (1997–2009

    Directory of Open Access Journals (Sweden)

    Chantal Babb

    2014-01-01

    Full Text Available Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA from the pathology based National Cancer Registry (1986–2006 and data on mortality (1997–2009 from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma. There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.

  10. Prostate cancer in South Africa: pathology based national cancer registry data (1986-2006) and mortality rates (1997-2009).

    Science.gov (United States)

    Babb, Chantal; Urban, Margaret; Kielkowski, Danuta; Kellett, Patricia

    2014-01-01

    Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA) from the pathology based National Cancer Registry (1986-2006) and data on mortality (1997-2009) from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR) using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma). There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA.

  11. Prostate Cancer in South Africa: Pathology Based National Cancer Registry Data (1986–2006) and Mortality Rates (1997–2009)

    Science.gov (United States)

    Babb, Chantal; Urban, Margaret; Kielkowski, Danuta; Kellett, Patricia

    2014-01-01

    Prostate cancer is one of the most common male cancers globally; however little is known about prostate cancer in Africa. Incidence data for prostate cancer in South Africa (SA) from the pathology based National Cancer Registry (1986–2006) and data on mortality (1997–2009) from Statistics SA were analysed. World standard population denominators were used to calculate age specific incidence and mortality rates (ASIR and ASMR) using the direct method. Prostate cancer was the most common male cancer in all SA population groups (excluding basal cell carcinoma). There are large disparities in the ASIR between black, white, coloured, and Asian/Indian populations: 19, 65, 46, and 19 per 100 000, respectively, and ASMR was 11, 7, 52, and 6 per 100 000, respectively. Prostate cancer was the second leading cause of cancer death, accounting for around 13% of male deaths from a cancer. The average age at diagnosis was 68 years and 74 years at death. For SA the ASIR increased from 16.8 in 1986 to 30.8 in 2006, while the ASMR increased from 12.3 in 1997 to 16.7 in 2009. There has been a steady increase of incidence and mortality from prostate cancer in SA. PMID:24955252

  12. 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.

  13. High death rates in health care workers and teachers in Malawi.

    Science.gov (United States)

    Harries, A D; Hargreaves, N J; Gausi, F; Kwanjana, J H; Salaniponi, F M

    2002-01-01

    High death rates are reported in health care workers (HCWs) and teachers in urban areas of Malawi. The present study was carried out to determine the annual death rate in HCWs and primary school teachers working in semi-urban and rural areas of Malawi, and to try to ascertain the main causes of death. Forty district and mission hospitals in Malawi were visited. A record was made of the number of clinical and nursing-based HCWs in each hospital in 1999, the number of deaths in that calendar year and reported causes of death. A record was also made of the number of teachers working in 4 primary schools nearest to each hospital in 1999, the number of deaths in that calendar year and reported causes of death. There were 2979 HCWs, of whom 60 (2.0%) died. There were 4367 teachers of whom 101 (2.3%) died. Annual death rates, calculated per 100,000 people, were significantly higher in male HCWs compared with female HCWs (2495 versus 1770, RR 1.17, 95% CI 1.14-1.20, P < 0.001), and significantly higher in female teachers compared with male teachers (2521 versus 1934, RR 1.14, 95% CI 1.11-1.17, P < 0.001). In male HCWs and teachers the highest death rates were in those aged 35-44 years. In female HCWs and teachers, the highest death rates were in those aged 25-34 years and 35-44 years, respectively. Reported causes of death in HCWs were tuberculosis (TB) in 47%, chronic illness in 45% and acute illness in the remainder, while in teachers the causes were TB in 27%, chronic illness in 49% and acute illness in 25%. Chronic illness, thought to be due to AIDS, and TB were the common causes of death. The current high death rates from AIDS and TB will have a crippling toll on the health and education sectors, and effective ways of reducing these death rates must be found.

  14. Biplot models applied to cancer mortality rates.

    Science.gov (United States)

    Osmond, C

    1985-01-01

    "A graphical method developed by Gabriel to display the rows and columns of a matrix is applied to tables of age- and period-specific cancer mortality rates. It is particularly useful when the pattern of age-specific rates changes with time. Trends in age-specific rates and changes in the age distribution are identified as projections. Three examples [from England and Wales] are given."

  15. Impaired Driving Death Rate, by Age and Gender, 2012 & 2014, 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, 2014. 2012 Source: Fatality Analysis...

  16. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012 & 2014, 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 & 2014. 2012 Source: Fatality Analysis Reporting System...

  17. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012 & 2014, 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 & 2014. 2012 Source: Fatality Analysis Reporting System...

  18. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012 & 2014, 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 & 2014. 2012 Source: Fatality Analysis Reporting System...

  19. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012 & 2014, 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 & 2014. 2012 Source: Fatality Analysis Reporting System...

  20. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012 & 2014, 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 & 2014. 2012 Source: Fatality Analysis Reporting System...

  1. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012 & 2014, 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 & 2014. 2012 Source: Fatality Analysis Reporting System...

  2. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012 & 2014, 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 & 2014. 2012 Source: Fatality Analysis Reporting System...

  3. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012 & 2014, 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 & 2014. 2012 Source: Fatality Analysis Reporting System...

  4. Impaired Driving Death Rate, by Age and Gender, 2012 & 2014, 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, 2014. 2012 Source: Fatality Analysis...

  5. 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...

  6. Motor Vehicle Occupant 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 motor vehicle occupants killed in crashes, 2012 & 2014. 2012 Source: Fatality Analysis Reporting System...

  7. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012 & 2014, 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 & 2014. 2012 Source: Fatality Analysis Reporting System...

  8. Impaired Driving Death Rate, by Age and Gender, 2012 & 2014, 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, 2014. 2012 Source: Fatality Analysis...

  9. Impaired Driving Death Rate, by Age and Gender, 2012 & 2014, 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, 2014. 2012 Source: Fatality Analysis...

  10. Impaired Driving Death Rate, by Age and Gender, 2012 & 2014, 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, 2014. 2012 Source: Fatality Analysis...

  11. Impaired Driving Death Rate, by Age and Gender, 2012 & 2014, 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, 2014. 2012 Source: Fatality Analysis...

  12. Motor Vehicle Occupant Death Rate, by Age and Gender, 2012 & 2014, 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 & 2014. 2012 Source: Fatality Analysis Reporting System...

  13. Impaired Driving Death Rate, by Age and Gender, 2012 & 2014, 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, 2014. 2012 Source: Fatality Analysis...

  14. Impaired Driving Death Rate, by Age and Gender, 2012 & 2014, 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, 2014. 2012 Source: Fatality Analysis...

  15. Impaired Driving Death Rate, by Age and Gender, 2012 & 2014, 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, 2014. 2012 Source: Fatality Analysis...

  16. Impaired Driving Death Rate, by Age and Gender, 2012 & 2014, 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, 2014. 2012 Source: Fatality Analysis...

  17. Quercetin-Induced Cell Death in Human Papillary Thyroid Cancer (B-CPAP Cells

    Directory of Open Access Journals (Sweden)

    Ergül Mutlu Altundağ

    2016-01-01

    Full Text Available In this study, we have investigated the antiproliferative effect of quercetin on human papillary thyroid cancer cells and determined the apoptotic mechanisms underlying its actions. We have used different concentrations of quercetin to induce apoptosis and measured cell viability. Apoptosis and cell cycle analysis was determined by flow cytometry using Annexin V and propidium iodide. Finally, we have measured changes in caspase-3 and cleaved poly(ADP-ribose polymerase (PARP protein expression levels as hallmarks of apoptosis and Hsp90 protein expression level as a marker of proteasome activity in treated and control cells. Quercetin treatment of human papillary thyroid cancer cells resulted in decreased cell proliferation and increased rate of apoptosis by caspase activation. Furthermore, it was demonstrated that quercetin induces cancer cell apoptosis by downregulating the levels of Hsp90. In conclusion, we have shown that quercetin induces downregulation of Hsp90 expression that may be involved in the decrease of chymotrypsin-like proteasome activity which, in order, induces inhibition of growth and causes cell death in thyroid cancer cells. Thus, quercetin appears to be a promising candidate drug for Hsp90 downregulation and apoptosis of thyroid cancer cells.

  18. 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.

  19. Cell Death Pathways in Photodynamic Therapy of Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mroz, Pawel, E-mail: pmroz@partners.org [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Dermatology, Harvard Medical School, Boston, MA 02114 (United States); Yaroslavsky, Anastasia [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Boston University College of Engineering, Boston, MA 02114 (United States); Kharkwal, Gitika B [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Dermatology, Harvard Medical School, Boston, MA 02114 (United States); Hamblin, Michael R. [Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114 (United States); Department of Dermatology, Harvard Medical School, Boston, MA 02114 (United States); Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139 (United States)

    2011-06-03

    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.

  20. Programmed death-1 : Therapeutic success after more than 100 years of cancer immunotherapy

    NARCIS (Netherlands)

    Dömling, Alexander; Holak, Tad A

    2014-01-01

    No other cancer therapy target class caused more excitement than the programmed death-1 (PD-1) pathway related. Antibodies against PD-1 and PD-1 ligands represent a therapeutic breakthrough and are the first examples of broadly efficacious and durable cancer immunotherapies. Cancer for the first tim

  1. 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.

    Science.gov (United States)

    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, 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; pDBD donors with 1.51 less transplants per DCD compared to DBD (95% CI: 1.23, 1.79; pDBD 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.

  2. 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.

  3. 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.

  4. 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.

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

    Science.gov (United States)

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

    2016-03-31

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

  6. 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.

  7. Skin Cancer Rates by Race and Ethnicity

    Science.gov (United States)

    ... Trends Behavior Rates What CDC Is Doing Skin Cancer Prevention Progress Report The Burning Truth Initiative A Base Tan Is Not a Safe Tan Tanned Skin Is Not Healthy Skin Controlled Tanning Is Not Safe Tanning Guidelines for School ... Melanoma Surveillance in the U.S. Related Links ...

  8. Sensitizing cancer cells to TRAIL-induced death by micellar delivery of mitoxantrone.

    Science.gov (United States)

    Grandhi, Taraka Sai Pavan; Potta, Thrimoorthy; Taylor, David J; Tian, Yanqing; Johnson, Roger H; Meldrum, Deirdre R; Rege, Kaushal

    2014-01-01

    TNFα-related apoptosis-inducing ligand (TRAIL) induces death selectively in cancer cells. However, subpopulations of cancer cells are either resistant to or can develop resistance to TRAIL-induced death. As a result, strategies that overcome this resistance are currently under investigation. We have recently identified several US FDA-approved drugs with TRAIL-sensitization activity against prostate, breast and pancreatic cancer cells. Mitoxantrone, a previously unknown TRAIL sensitizer identified in the screen, was successfully encapsulated in methoxy-, amine- and carboxyl-terminated PEG-DSPE micelles in order to facilitate delivery of the drug to cancer cells. All three micelle types were extensively characterized for their physicochemical properties and evaluated for their ability to sensitize cancer cells to TRAIL-induced death. Our results indicate that micelle-encapsulated mitoxantrone can be advantageously employed in synergistic treatments with TRAIL, leading to a biocompatible delivery system and amplified cell killing activity for combination chemotherapeutic cancer treatments.

  9. 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.

  10. 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

  11. Predictors of loco-regional recurrence and cancer-related death after breast cancer surgery.

    Science.gov (United States)

    Rausei, Stefano; Rovera, Francesca; Dionigi, Gianlorenzo; Tornese, Deborah; Fachinetti, Anna; Boni, Luigi; Dionigi, Renzo

    2010-01-01

    To determine which tumor-related factors might predispose the patient to loco-regional recurrence or death and the impact of these factors on the different types of events. We retrospectively analyzed the data of 1991 women between January 1998 and March 2010 for a first primary nonmetastatic breast cancer and treated with surgery and neo-adjuvant/adjuvant therapy. The overall survival distribution was estimated using the Kaplan-Meier method. The prognostic impact of several factors on cumulative overall and loco-regional recurrence free survival was evaluated by univariate (log-rank test) and multivariate analysis (Cox regression). At log-rank test, pT, nodal status, histotype, grading, lymphangioinvasive growth, tumor diameter, estrogen receptors (ER) status, progesterone receptors (PR) status, expression of Ki67, and expression of Her2/neu had a prognostic value on loco-regional recurrence or overall survival. In the multivariate analysis grading remained the only independent predictor of loco-regional recurrences. With regard to overall survival, the Cox model selected grading along with nodal status and PR status. Loco-regional recurrences after breast cancer surgery are not frequent events. They are markers of tumor aggressiveness and predictor of an increased likelihood of cancer-related death. However, loco-regional recurrence and systemic tumor progression are partially independent events, since some prognostic factors differ.

  12. ERG rearrangement is associated with prostate cancer-related death in Chinese prostate cancer patients.

    Directory of Open Access Journals (Sweden)

    Mei Qi

    Full Text Available Recently, ETS-related gene (ERG gene rearrangements, phosphatase tensin homologue (PTEN deletions and EGFR family aberrations were characterized as potential biomarkers for prostate cancer (PCa patient management. Although ERG gene rearrangement has been identified in approximately 50% of localized prostate cancers in western countries, the prognostic significance of this critical molecular event remains unknown in Chinese patients. Using fluorescence in situ hybridization (FISH and immunohistochemistry, we evaluated ERG, PTEN and EGFR family aberrations in a cohort of 224 Chinese prostate cancer patients diagnosed in transurethral resection of the prostate (TUR-P. Overall, ERG rearrangement was detected in 23.2% (44/190 cases, of which 54.5% (24/44 showed deletion of the 5'end of ERG. PTEN deletion was identified in 10.8% (19/176 cases. Amplification of EGFR and HER2 genes was present in 1.1% (2/178 and 5.8% (10/173 of cases, respectively. Significant correlation between ERG rearrangement and PTEN deletion was identified in this cohort. EGFR and HER2 aberrations occurred more frequently in PCas without ERG rearrangement than in those with ERG rearrangement, although this did not reach statistical significance. Overall, ERG rearrangement was associated with pre-operative PSA values (P = 0.038 and cancer-related death (P = 0.02, but not with the age, clinical T stage, Gleason score, or Ki-67 labeling index (LI. Notably, multivariate analysis including known prognostic markers revealed ERG rearrangement was an independent prognostic factor (P = 0.022. Additionally, ERG rearrangement status was helpful to identify patients with poor prognosis from PCa group with low Ki-67 LI. In summary, we reported that ERG rearrangement was associated with cancer-related death in Chinese PCa patients. Determination of ERG rearrangement status allows stratification of PCa patients into different survival categories.

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

    Science.gov (United States)

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

    2014-01-01

    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 modified maximum likelihood produced similar results when we assumed that the specificity of outcome classification was 0.98. With sensitivity assumed to be 0.80 and specificity assumed to be 0.95, estimated rate ratios were further from the null and less precise (rate ratio = 2.17; 95% confidence interval: 1.59, 2.98). In the present context, standard estimates for the effect of asbestos on lung cancer death were similar to estimates accounting for the limited misclassification. However, sensitivity analysis using modified maximum likelihood was needed to verify the robustness of standard estimates, and this approach will provide unbiased estimates in settings with more misclassification. PMID:24352593

  14. Low Frequency of Programmed Death Ligand 1 Expression in Pediatric Cancers

    OpenAIRE

    2016-01-01

    Programmed death 1 (PD‐1)/programmed death ligand 1 (PD‐L1) pathway blockade has become a promising therapeutic target in adult cancers. We evaluated PD‐L1 expression and tumor‐infiltrating CD8+ T cells in formalin‐fixed, paraffin‐embedded tumor specimens from 53 untreated pediatric patients with eight cancer types: neuroblastoma, extracranial malignant germ cell tumor, hepatoblastoma, germinoma, medulloblastoma, renal tumor, rhabdomyosarcoma, and atypical teratoid/rhabdoid tumor. One rhabdom...

  15. Association between resting heart rate and coronary artery disease, stroke, sudden death and noncardiovascular diseases: a meta-analysis

    Science.gov (United States)

    Zhang, Dongfeng; Wang, Weijing; Li, Fang

    2016-01-01

    Background: Resting heart rate is linked to risk of coronary artery disease, stroke, sudden death and noncardiovascular diseases. We conducted a meta-analysis to assess these associations in general populations and in populations of patients with hypertension or diabetes mellitus. Methods: We searched PubMed, Embase and MEDLINE from inception to Mar. 5, 2016. We used a random-effects model to combine study-specific relative risks (RRs). We used restricted cubic splines to assess the dose–response relation. Results: We included 45 nonrandomized prospective cohort studies in the meta-analysis. The multivariable adjusted RR with an increment of 10 beats/min in resting heart rate was 1.12 (95% confidence interval [CI] 1.09–1.14) for coronary artery disease, 1.05 (95% CI 1.01–1.08) for stroke, 1.12 (95% CI 1.02–1.24) for sudden death, 1.16 (95% CI 1.12–1.21) for noncardiovascular diseases, 1.09 (95% CI 1.06–1.12) for all types of cancer and 1.25 (95% CI 1.17–1.34) for noncardiovascular diseases excluding cancer. All of these relations were linear. In an analysis by category of resting heart rate ( 80 beats/min), the RRs were 0.99 (95% CI 0.93–1.04), 1.08 (95% CI 1.01–1.16) and 1.30 (95% CI 1.19–1.43), respectively, for coronary artery disease; 1.08 (95% CI 0.98–1.19), 1.11 (95% CI 0.98–1.25) and 1.08 (95% CI 0.93–1.25), respectively, for stroke; and 1.17 (95% CI 0.94–1.46), 1.31 (95% CI 1.12–1.54) and 1.57 (95% CI 1.39–1.77), respectively, for noncardiovascular diseases. After excluding studies involving patients with hypertension or diabetes, we obtained similar results for coronary artery disease, stroke and noncardiovascular diseases, but found no association with sudden death. Interpretation: Resting heart rate was an independent predictor of coronary artery disease, stroke, sudden death and noncardiovascular diseases over all of the studies combined. When the analysis included only studies concerning general populations, resting

  16. Heparin based prophylaxis to prevent venous thromboembolic events and death in patients with cancer - a subgroup analysis of CERTIFY

    Directory of Open Access Journals (Sweden)

    Abletshauser Claudia

    2011-07-01

    Full Text Available Abstract Background Patients with cancer have an increased risk of VTE. We compared VTE rates and bleeding complications in 1 cancer patients receiving LMWH or UFH and 2 patients with or without cancer. Methods Acutely-ill, non-surgical patients ≥70 years with (n = 274 or without cancer (n = 2,965 received certoparin 3,000 UaXa o.d. or UFH 5,000 IU t.i.d. for 8-20 days. Results 1 Thromboembolic events in cancer patients (proximal DVT, symptomatic non-fatal PE and VTE-related death occurred at 4.50% with certoparin and 6.03% with UFH (OR 0.73; 95% CI 0.23-2.39. Major bleeding was comparable and minor bleedings (0.75 vs. 5.67% were nominally less frequent. 7.5% of certoparin and 12.8% of UFH treated patients experienced serious adverse events. 2 Thromboembolic event rates were comparable in patients with or without cancer (5.29 vs. 4.13% as were bleeding complications. All cause death was increased in cancer (OR 2.68; 95%CI 1.22-5.86. 10.2% of patients with and 5.81% of those without cancer experienced serious adverse events (OR 1.85; 95% CI 1.21-2.81. Conclusions Certoparin 3,000 UaXa o.d. and 5,000 IU UFH t.i.d. were equally effective and safe with respect to bleeding complications in patients with cancer. There were no statistically significant differences in the risk of thromboembolic events in patients with or without cancer receiving adequate anticoagulation. Trial Registration clinicaltrials.gov, NCT00451412

  17. Parental Perceptions of Siblings' Grieving after a Childhood Cancer Death: A Longitudinal Study

    Science.gov (United States)

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

    2013-01-01

    We investigated longitudinally parental perceptions of siblings' bereavement after childhood cancer death. Parents were interviewed 6 months (n = 25) and 18 months (n = 15) post-death. Data are analyzed combined and over time. The following themes emerged: (a) expression of grief: missing deceased child (verbally, crying), behavioral problems,…

  18. 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.

  19. Falling Plasmodium knowlesi Malaria Death Rate among Adults despite Rising Incidence, Sabah, Malaysia, 2010-2014.

    Science.gov (United States)

    Rajahram, Giri S; Barber, Bridget E; William, Timothy; Grigg, Matthew J; Menon, Jayaram; Yeo, Tsin W; Anstey, Nicholas M

    2016-01-01

    Deaths from Plasmodium knowlesi malaria have been linked to delayed parenteral treatment. In Malaysia, early intravenous artesunate is now recommended for all severe malaria cases. We describe P. knowlesi fatalities in Sabah, Malaysia, during 2012-2014 and report species-specific fatality rates based on 2010-2014 case notifications. Sixteen malaria-associated deaths (caused by PCR-confirmed P. knowlesi [7], P. falciparum [7], and P. vivax [1] and microscopy-diagnosed "P. malariae" [1]) were reported during 2012-2014. Six patients with severe P. knowlesi malaria received intravenous artesunate at hospital admission. For persons ≥15 years of age, overall fatality rates during 2010-2014 were 3.4, 4.2, and 1.0 deaths/1,000 P. knowlesi, P. falciparum, and P. vivax notifications, respectively; P. knowlesi-associated fatality rates fell from 9.2 to 1.6 deaths/1,000 notifications. No P. knowlesi-associated deaths occurred among children, despite 373 notified cases. Although P. knowlesi malaria incidence is rising, the notification-fatality rate has decreased, likely due to improved use of intravenous artesunate.

  20. Does childhood cancer affect parental divorce rates? A population-based study.

    Science.gov (United States)

    Syse, Astri; Loge, Jon H; Lyngstad, Torkild H

    2010-02-10

    PURPOSE Cancer in children may profoundly affect parents' personal relationships in terms of psychological stress and an increased care burden. This could hypothetically elevate divorce rates. Few studies on divorce occurrence exist, so the effect of childhood cancers on parental divorce rates was explored. PATIENTS AND METHODS Data on the entire Norwegian married population, age 17 to 69 years, with children age 0 to 20 years in 1974 to 2001 (N = 977,928 couples) were retrieved from the Cancer Registry, the Central Population Register, the Directorate of Taxes, and population censuses. Divorce rates for 4,590 couples who were parenting a child with cancer were compared with those of otherwise similar couples by discrete-time hazard regression models. Results Cancer in a child was not associated with an increased risk of parental divorce overall. An increased divorce rate was observed with Wilms tumor (odds ratio [OR], 1.52) but not with any of the other common childhood cancers. The child's age at diagnosis, time elapsed from diagnosis, and death from cancer did not influence divorce rates significantly. Increased divorce rates were observed for couples in whom the mothers had an education greater than high school level (OR, 1.16); the risk was particularly high shortly after diagnosis, for CNS cancers and Wilms tumors, for couples with children 0 to 9 years of age at diagnosis, and after a child's death. CONCLUSION This large, registry-based study shows that cancer in children is not associated with an increased parental divorce rate, except with Wilms tumors. Couples in whom the wife is highly educated appear to face increased divorce rates after a child's cancer, and this may warrant additional study.

  1. 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

  2. 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…

  3. Serum copper and zinc and the risk of death from cancer and cardiovascular disease

    NARCIS (Netherlands)

    F.J. Kok (Frans); C.M. van Duijn (Cock); F.A. de Wolf; H.A. Valkenburg (Hans); A. Hofman (Albert)

    1988-01-01

    textabstractTo investigate the association of serum copper and zinc with mortality from cancer and cardiovascular disease, the authors performed a case-control analysis of data obtained in a Dutch prospective follow-up study. Cancer (n = 64) and cardiovascular disease (n = 62) deaths and their match

  4. 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

  5. Apparent exchange rate for breast cancer characterization.

    Science.gov (United States)

    Lasič, Samo; Oredsson, Stina; Partridge, Savannah C; Saal, Lao H; Topgaard, Daniel; Nilsson, Markus; Bryskhe, Karin

    2016-05-01

    Although diffusion MRI has shown promise for the characterization of breast cancer, it has low specificity to malignant subtypes. Higher specificity might be achieved if the effects of cell morphology and molecular exchange across cell membranes could be disentangled. The quantification of exchange might thus allow the differentiation of different types of breast cancer cells. Based on differences in diffusion rates between the intra- and extracellular compartments, filter exchange spectroscopy/imaging (FEXSY/FEXI) provides non-invasive quantification of the apparent exchange rate (AXR) of water between the two compartments. To test the feasibility of FEXSY for the differentiation of different breast cancer cells, we performed experiments on several breast epithelial cell lines in vitro. Furthermore, we performed the first in vivo FEXI measurement of water exchange in human breast. In cell suspensions, pulsed gradient spin-echo experiments with large b values and variable pulse duration allow the characterization of the intracellular compartment, whereas FEXSY provides a quantification of AXR. These experiments are very sensitive to the physiological state of cells and can be used to establish reliable protocols for the culture and harvesting of cells. Our results suggest that different breast cancer subtypes can be distinguished on the basis of their AXR values in cell suspensions. Time-resolved measurements allow the monitoring of the physiological state of cells in suspensions over the time-scale of hours, and reveal an abrupt disintegration of the intracellular compartment. In vivo, exchange can be detected in a tumor, whereas, in normal tissue, the exchange rate is outside the range experimentally accessible for FEXI. At present, low signal-to-noise ratio and limited scan time allows the quantification of AXR only in a region of interest of relatively large tumors.

  6. Childhood Cancer Death Rates Continue to Fall: CDC

    Science.gov (United States)

    ... Earlier this week, the group announced a new campaign to fund additional research aimed at pediatric brain ... to keep refining treatment regimens to limit any negative effects on kids' long-term health. The findings ...

  7. Study: California Ethnic Groups Seeing Increased Cancer Rates

    Science.gov (United States)

    Black Issues in Higher Education, 2005

    2005-01-01

    A statewide study on cancer and ethnicity hints that cancer rates among immigrant groups may be tied to their degree of assimilation into American culture. The study, released by the University of Southern California's Norris Comprehensive Cancer Center, marks the first statewide look at cancer rates among Vietnamese and South Asians and provides…

  8. Evaluating prostate cancer mortality and competing risks of death in patients with localized prostate cancer using a comprehensive nomogram

    OpenAIRE

    Kutikov, A.; Cooperberg, MR; Paciorek, AT; Uzzo, RG; Carroll, PR; Boorjian, SA

    2012-01-01

    BACKGROUND: The aim of this study was to determine the optimal treatment for a patient with newly diagnosed prostate cancer weighing the individual's risk of disease progression against his risk of non-cancer death.METHODS: We developed a predictive model incorporating clinicopathological tumor variables, patient age, comorbidity status, and primary treatment modality. We identified 6091 patients with clinically-localized prostate cancer managed with radical prostatectomy (n4117) or radiation...

  9. L2-Algebraic Decay Rate for Transient Birth-Death Processes

    Institute of Scientific and Technical Information of China (English)

    Lijuan CHENG; Yingzhe WANG

    2012-01-01

    This paper is a continuation of the study of the algebraic speed for Markov processes.The authors concentrate on algebraic decay rate for the transient birth-death processes.According to the classification of the boundaries,a series of the sufficient conditions for algebraic decay is presented.To illustrate the power of the results,some examples are included.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  11. Death Does Matter--Cancer Risk in Patients With End-Stage Renal Disease: A Nationwide Population-Based Study With Competing Risk Analyses.

    Science.gov (United States)

    Weng, Shih-Feng; Chiu, Yu-Hsien; Jan, Ren-Long; Chen, Yi-Chen; Chien, Chih-Chiang; Wang, Jhi-Joung; Chu, Chin-Chen

    2016-01-01

    Patients with end-stage renal disease (ESRD) have a high mortality rate. We hypothesized that not accounting for death as a competing risk overestimates the event rate caused by ESRD. Thus, we examined the cancer risk for patients with ESRD (ESRD) after death as a competing risk event had been adjusted for. Patients with newly diagnosed ESRD (n = 64,299) between 1999 and 2007, together with age- and sex-matched controls without ESRD (ESRD) (n = 128,592) were enrolled (1:2). In a Cox proportional hazards model that included death as a competing risk, ESRD patients in Taiwan had a lower overall incidence (subdistribution hazard ratio [sdHR] = 1.29) of cancer than did ESRD patients in a Cox model that did not include death as a competing risk (HR = 1.70). After competing mortality had been adjusted for, ESRD patients ≥70 (sdHR = 0.82) and ESRD patients on long-term dialysis (> 5 follow-up years, sdHR = 0.62), had a lower risk for developing cancer than did ESRD patients. This finding supported our hypothesis that standard survival analyses overestimate the event rate, especially when the mortality rate is high. It also showed that ESRD patients, when they grow older, were far less likely to develop cancer and far more likely to die because of underlying illnesses that might also affect the risk of death because of ESRD.

  12. Nationwide population-based study of cause-specific death rates in patients with psoriasis

    DEFF Research Database (Denmark)

    Salahadeen, E; Torp-Pedersen, C; Gislason, G;

    2015-01-01

    with severe psoriasis. The age at time of death varied by psoriasis status, i.e. 76.5 ± 14.0, 74.4 ± 12.8 and 72.0 ± 13.4 years, for the general population, mild psoriasis and severe psoriasis respectively. In general, the highest death rates were observed in patients with severe psoriasis. Overall death...... and nationwide data have not been presented previously. METHODS: In a nationwide population-based cohort we evaluated all-cause and cause-specific death rates in patients with psoriasis as compared to the general population. RESULTS: The entire Danish population aged 18 and above, corresponding to a total of 5......,458,627 individuals (50.7% female, 40.9 years ± 19.7), including 94,069 with mild psoriasis (53% female, 42.0 ± 17.0 years) and 28,253 with severe psoriasis (53.4% female, 43.0 ± 16.5 years), was included. A total of 884,661 deaths were recorded, including 10 916 in patients with mild psoriasis and 3699 in patients...

  13. 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.

  14. Programmed death ligand 2 in cancer-induced immune suppression.

    NARCIS (Netherlands)

    Rozali, E.N.; Hato, S.V.; Robinson, B.W.; Lake, R.A.; Lesterhuis, W.J.

    2012-01-01

    Inhibitory molecules of the B7/CD28 family play a key role in the induction of immune tolerance in the tumor microenvironment. The programmed death-1 receptor (PD-1), with its ligands PD-L1 and PD-L2, constitutes an important member of these inhibitory pathways. The relevance of the PD-1/PD-L1 pathw

  15. Mitochondria in cancer: at the crossroads of life and death

    Institute of Scientific and Technical Information of China (English)

    Vanessa C. Fogg; Nathan J. Lanning; Jeffrey P. MacKeigan

    2011-01-01

    Mitochondrial processes play an important role in tumor initiation and progression. In this review, we focus on three critical processes by which mitochondrial function may contribute to cancer: through alterations in glucose metabolism, the production of reactive oxygen species (ROS) and compromise of intrinsic apoptotic function. Alterations in cancer glucose metabolism include the Warburg effect, leading to a shift in metabolism away from aerobic respiration toward glycolysis, even when sufficient oxygen is present to support respiration. Such alterations in cellular metabolism may favor tumor cell growth by increasing the availability of biosynthetic intermediates needed for cellular growth and proliferation.Mutations in specific metabolic enzymes, namely succinate dehydrogenase, fumarate hydratase and the isocitrate dehydrogenases, have been linked to human cancer.Mitochondrial ROS may contribute to cancer via DNA damage and the activation of aberrant signaling pathways. ROS-dependent stabilization of the transcription factor hypoxia-inducible factor(HIF) may be a particularly important event for tumorigenesis. Compromised function of intrinsic apoptosis removes an important cellular safeguard against cancer and has been implicated in tumorigenesis, tumor metastasis, and chemoresistance. Each of the major mitochondrial processes is linked. In this review, we outline the connections between them and address ways these mitochondrial pathways may be targeted for cancer therapy.

  16. Survival rate of breast cancer patients in Malaysia: a population-based study.

    Science.gov (United States)

    Abdullah, Nor Aini; Wan Mahiyuddin, Wan Rozita; Muhammad, Nor Asiah; Ali, Zainudin Mohamad; Ibrahim, Lailanor; Ibrahim Tamim, Nor Saleha; Mustafa, Amal Nasir; Kamaluddin, Muhammad Amir

    2013-01-01

    Breast cancer is the most common cancer among Malaysian women. Other than hospital-based results, there are no documented population-based survival rates of Malaysian women for breast cancers. This population- based retrospective cohort study was therefore conducted. Data were obtained from Health Informatics Centre, Ministry of Health Malaysia, National Cancer Registry and National Registration Department for the period from 1st Jan 2000 to 31st December 2005. Cases were captured by ICD-10 and linked to death certificates to identify the status. Only complete data were analysed. Survival time was calculated from the estimated date of diagnosis to the date of death or date of loss to follow-up. Observed survival rates were estimated by Kaplan- Meier method using SPSS Statistical Software version 17. A total of 10,230 complete data sets were analysed. The mean age at diagnosis was 50.6 years old. The overall 5-year survival rate was 49% with median survival time of 68.1 months. Indian women had a higher survival rate of 54% compared to Chinese women (49%) and Malays (45%). The overall 5-year survival rate of breast cancer patient among Malaysian women was still low for the cohort of 2000 to 2005 as compared to survival rates in developed nations. Therefore, it is necessary to enhance the strategies for early detection and intervention.

  17. 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;}

  18. Low zinc environment induces stress signaling, senescence and mixed cell death modalities in colon cancer cells.

    Science.gov (United States)

    Rudolf, Emil; Rudolf, Kamil

    2015-12-01

    Currently it is not clear what type of the final cellular response (i.e. cell death modality or senescence) is induced upon chronic intracellular zinc depletion in colon cancer cells. To address this question, isogenic colon cancer lines SW480 and SW620 exposed to low zinc environment were studied over the period of 6 weeks. Low zinc environment reduced total as well as free intracellular zinc content in both cell lines. Decreased intracellular zinc content resulted in changes in cellular proliferation, cell cycle distribution and activation of stress signaling. In addition, colonocytes with low zinc content displayed increased levels of oxidative stress, changes in mitochondrial activity but in the absence of significant DNA damage. Towards the end of treatment (4th-6th week), exposed cells started to change morphologically, and typical markers of senescence as well as cell death appeared. Of two examined colon cancer cell lines, SW480 cells proved to activate predominantly senescent phenotype, with frequent form of demise being necrosis and mixed cell death modality but not apoptosis. Conversely, SW620 cells activated mostly cell death, with relatively equal distribution of apoptosis and mixed types, while senescent phenotypes and necrosis were present only in a small fraction of cell populations. Addition of zinc at the beginning of 4th week of treatment significantly suppressed cell death phenotypes in both cell lines but had no significant effect on senescence. In conclusion, presented results demonstrate variability of responses to chronic zinc depletion in colon cancer as modeled in vitro.

  19. 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.

  20. Risk for prostate cancer by occupation and industry: a 24-state death certificate study.

    Science.gov (United States)

    Krstev, S; Baris, D; Stewart, P A; Hayes, R B; Blair, A; Dosemeci, M

    1998-11-01

    Current knowledge of the etiology of prostate cancer is limited. Numerous studies have suggested that certain occupations and industries may be associated with the occurrence of prostate cancer. Information on occupation and industry on death certificates from 24 states gathered from 1984 to 1993 was used in case control study on prostate cancer. A total of 60,878 men with prostate cancer as underlying cause of death was selected and matched with controls who died of all other causes except cancer. Similar to the findings of our parallel large case control study of prostate cancer, we observed excess risks in some white-collar occupations, such as administrators, managers, teachers, engineers, and sales occupations. However, some blue-collar occupations, such as power plant operators and stationary engineers, brickmasons, machinery maintenance workers, airplane pilots, longshoreman, railroad industry workers, and other occupations with potential exposure to PAH also showed risk of excess prostate cancer. Risk was significantly decreased for blue-collar occupations, including farm workers, commercial fishermen, mechanics and repairers, structural metal workers, mining, printing, winding, dry cleaning, textile machine operators, cooks, bakers, and bartenders. Although we observed excess risks of prostate cancer among some low socioeconomic status (SES) occupations, the overall results suggest that the effects of higher SES cannot be ruled out in associations between occupational factors and the risk of prostate cancer.

  1. 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

  2. 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.

  3. Estimating Survival Rates in Gastric Cancer Based on Pathologic and Demographic Factors in Fars Cancer Registry (2001-2005

    Directory of Open Access Journals (Sweden)

    Rajaeifard Abdolreza

    2009-03-01

    Full Text Available Background: Gastric cancer remains as one of the leading causes of death worldwide. In patients with gastric cancer, the survival rate after diagnosis is relatively low. The present study aimed to evaluate the impact of demographic factors in estimation of survival rate in patients with gastric cancer in order to develop updated documents in these patients. Materials and Methods: All gastric cancer patients registered in Fars cancer registry from 2001-2006 were entered in the study. Vital status of the patients was asked by telephone contact. Survival rates were estimated using Kaplan-Meier method and compared by Log-rank test. All calculations were performed using STATA (v.8 software. The p value0.05. Conclusion: Our results showed that the survival rates of gastric cancer patients in our study were relatively low. Late diagnosis and delayed therapy are important reasons for low survival in these patients. Therefore, improving public education about primary symptoms of gastric cancer by media is recommended

  4. Changes in and Impact of the Death Review Process in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

    Science.gov (United States)

    Miller, Anthony B; Feld, Ronald; Fontana, Robert; Gohagan, John K; Jatoi, Ismail; Lawrence, Walter; Miller, Amy; ProroK, Philip C; Rajput, Ashwani; Sherman, Morris; Welch, Gilbert; Wright, Patrick; Yurgalevitch, Susan; Albertsen, Peter

    2015-01-01

    Death review was conducted for the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial to avoid the biases associated with causes of death entered on death certificates. An algorithm selected deaths for review. Records on diagnosis and terminal illness were perused in the coordinating center and by the chair of the death review committee (DRC). Identifying information and randomization arm was removed. Three reviewers independently determined the cause of death. Disagreement was resolved at a meeting of the DRC. This process was subsequently simplified. The cause of death was determined by one DRC member and compared to the death certificate. With agreement the case was finalized. When discordant, the records were sent to a second DRC member. If the reviewers agreed, the case was finalized. If not, a third member reviewed. If two of the three reviewers agreed, the case was sent back to the discordant reviewer. If the reviewer remained discordant the case was resolved by a conference call. Of the 4728 death reviews that were completed, the DRC confirmed the death certificate underlying cause for over 90%. Between 5% and 13% of the certified deaths were regarded as indirect causes of death, associated with the treatment of the ascertained cancer; differential for prostate cancer, 11% in the intervention arm and 6% in the control. Without review, between 1% and 6% of the deaths that occurred would not have been assigned to the relevant PLCO cancer. The DRC completed 76% of those requiring review before the process ceased.

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

    OpenAIRE

    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 criminal conduct and mortality rates in the Netherlands using data from the Criminal Careers and Life Course Study, which traces the life course and criminal careers of 4,615 males and females convict...

  6. Ursodeoxycholic Acid Induces Death Receptor-mediated Apoptosis in Prostate Cancer Cells

    Science.gov (United States)

    Lee, Won Sup; Jung, Ji Hyun; Panchanathan, Radha; Yun, Jeong Won; Kim, Dong Hoon; Kim, Hye Jung; Kim, Gon Sup; Ryu, Chung Ho; Shin, Sung Chul; Hong, Soon Chan; Choi, Yung Hyun; Jung, Jin-Myung

    2017-01-01

    Background Bile acids have anti-cancer properties in a certain types of cancers. We determined anticancer activity and its underlying molecular mechanism of ursodeoxycholic acid (UDCA) in human DU145 prostate cancer cells. Methods Cell viability was measured with an MTT assay. UDCA-induced apoptosis was determined with flow cytometric analysis. The expression levels of apoptosis-related signaling proteins were examined with Western blotting. Results UDCA treatment significantly inhibited cell growth of DU145 in a dose-dependent manner. It induced cellular shrinkage and cytoplasmic blebs and accumulated the cells with sub-G1 DNA contents. Moreover, UDCA activated caspase 8, suggesting that UDCA-induced apoptosis is associated with extrinsic pathway. Consistent to this finding, UDCA increased the expressions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor, death receptor 4 (DR4) and death receptor 5 (DR5), and TRAIL augmented the UDCA-induced cell death in DU145 cells. In addition, UDCA also increased the expressions of Bax and cytochrome c and decreased the expression of Bcl-xL in DU145 cells. This finding suggests that UDCA-induced apoptosis may be involved in intrinsic pathway. Conclusions UDCA induces apoptosis via extrinsic pathway as well as intrinsic pathway in DU145 prostate cancer cells. UDCA may be a promising anti-cancer agent against prostate cancer.

  7. Heart Rate Distribution and Cause-specific Death in General Population of South China

    Institute of Scientific and Technical Information of China (English)

    Liu Xiaoqing; Rao Xuxu; Mai Jinzhuang; Wu Yong; Guo Chenye; Shi Meiling; Gao Xiangmin; Deng Mulan; Lian Zibing

    2005-01-01

    Objectives To analyses heart rate (HR) distribution of healthy adults in the south China community and evaluate relative risk of HR to total cause of death and cardiac cerebral vascular death. Methods Analytical data come from the baseline survey and follow-up visits in the PRC-USA Collaborative Study of Cardiovascular Epidemiology in urban and rural samples of Guangzhou. The baseline survey was initiated in 1983 and 1984, and rescanned in 1987 and 1988. Since 1991 Follow-up visits for endpoint events were carried once every two years.Average follow-up year was 16.2 from baseline to 2000.People excluded from cardiac cerebral vascular disease, diabetes and other various chronic diseases were regarded as "healthy adults". Heart rates of these subjects were measured on resting electrocardiogram.Endpoint evens include: total cause of death, first attack of coronary disease and cerebral vascular events.SAS software was used for analysis. Cox Proportional Hazards model was used to evaluate the impact of HR on total death and cardiac cerebral vascular disease.Results A total of 4570 men and women aged 35-55years from urban and rural Guangzhou were investigated. 3493 healthy subjects were enrolled in the analysis, including 1694 men and 1799 women. Mean of theHRis (67.9±10.6) beats/min (bpm) in the whole population, ( 66.3 ± 10.7 ) bpm in men and (69.3 ±10.4) in women. The 5th percentile of the HR was 51 in men and 54 in women. The 95th percentile of the HR was 85 in men and 88 in women. Single correlation analysis showed there was negative relationship between age and HR, but it was only statistical significant in female. Analysis with Cox Proportional Hazards model show that HR < 50 bpm tops the risk of total causes of death (1.725)and HR 50-59 bpm decreased the risk of total causes of death (0.843).Relative risk of cardiac cerebral vascular events exceeds 1 when HR < 50 and >90 bpm (1.486 and 7.008 respectively). It was less than 1 in other groups but there was

  8. 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'.

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

    Science.gov (United States)

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

    2016-01-01

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

  10. Dynamic prediction of risk of death using history of cancer recurrences in joint frailty models.

    Science.gov (United States)

    Mauguen, Audrey; Rachet, Bernard; Mathoulin-Pélissier, Simone; MacGrogan, Gaetan; Laurent, Alexandre; Rondeau, Virginie

    2013-12-30

    Evaluating the prognosis of patients according to their demographic, biological, or disease characteristics is a major issue, as it may be used for guiding treatment decisions. In cancer studies, typically, more than one endpoint can be observed before death. Patients may undergo several types of events, such as local recurrences and distant metastases, with death as the terminal event. Accuracy of clinical decisions may be improved when the history of these different events is considered. Thus, it may be useful to dynamically predict patients' risk of death using recurrence history. As previously applied within the framework of joint models for longitudinal and time to event data, we propose a dynamic prediction tool based on joint frailty models. Joint modeling accounts for the dependence between recurrent events and death, by the introduction of a random effect shared by the two processes. We estimate the probability of death between the prediction time t and a horizon t + w, conditional on information available at time t. Prediction can be updated with the occurrence of a new event. We proposed and compared three prediction settings, taking into account three different information levels. The proposed tools are applied to patients diagnosed with a primary invasive breast cancer and treated with breast-conserving surgery, followed for more than 10 years in a French comprehensive cancer center.

  11. 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.

  12. 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

  13. A death certificate analysis of nasal cancer among furniture workers in North Carolina.

    Science.gov (United States)

    Brinton, L A; Blot, W J; Stone, B J; Fraumeni, J F

    1977-10-01

    A case-control study of nasal cancer, based on death certificate statements on occupation in North Carolina counties with furniture-manufacturing industries, revealed a 4-fold excess risk linked to this occupation. Although woodworking exposures have been associated with nasal adenocarcinomas in several areas of the world, this is the first report of such a relationship in the United States.

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

    Science.gov (United States)

    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…

  15. 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.

  16. 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…

  17. Non-oncogenic Acute Viral Infections Disrupt Anti-cancer Responses and Lead to Accelerated Cancer-Specific Host Death

    Directory of Open Access Journals (Sweden)

    Frederick J. Kohlhapp

    2016-10-01

    Full Text Available In light of increased cancer prevalence and cancer-specific deaths in patients with infections, we investigated whether infections alter anti-tumor immune responses. We report that acute influenza infection of the lung promotes distal melanoma growth in the dermis and leads to accelerated cancer-specific host death. Furthermore, we show that during influenza infection, anti-melanoma CD8+ T cells are shunted from the tumor to the infection site, where they express high levels of the inhibitory receptor programmed cell death protein 1 (PD-1. Immunotherapy to block PD-1 reverses this loss of anti-tumor CD8+ T cells from the tumor and decreases infection-induced tumor growth. Our findings show that acute non-oncogenic infection can promote cancer growth, raising concerns regarding acute viral illness sequelae. They also suggest an unexpected role for PD-1 blockade in cancer immunotherapy and provide insight into the immune response when faced with concomitant challenges.

  18. p53 family members - important messengers in cell death signaling in photodynamic therapy of cancer?

    Science.gov (United States)

    Acedo, Pilar; Zawacka-Pankau, Joanna

    2015-08-01

    TP53 is one of the genes most frequently inactivated in cancers. Mutations in TP53 gene are linked to worse prognosis and shorter overall survival of cancer patients. TP53 encodes a critical tumor suppressor, which dictates cell fate decisions upon stress stimuli. As a sensor of cellular stress, p53 is a relevant messenger of cell death signaling in ROS-driven photodynamic therapy (PDT) of cancer. The significant role of p53 in response to PDT has been reported for several clinically approved photosensitizers. Multiple reports described that wild-type p53 contributes to cell killing upon photodynamic therapy with clinically approved photosensitizers but the mechanism is still not fully understood. This work outlines the diverse functions of p53 family members in cancer cells' susceptibility and resistance to PDT. In summary p53 and p53 family members are emerging as important mediators of cell death signaling in photodynamic therapy of cancer, however the mechanism of cell death provoked during PDT might differ depending on the tissue type and the photosensitizer applied.

  19. Rapid and efficient cancer cell killing mediated by high-affinity death receptor homotrimerizing TRAIL variants.

    Science.gov (United States)

    Reis, C R; van der Sloot, A M; Natoni, A; Szegezdi, E; Setroikromo, R; Meijer, M; Sjollema, K; Stricher, F; Cool, R H; Samali, A; Serrano, L; Quax, W J

    2010-10-21

    The tumour necrosis factor family member TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in a variety of cancer cells through the activation of death receptors 4 (DR4) and 5 (DR5) and is considered a promising anticancer therapeutic agent. As apoptosis seems to occur primarily via only one of the two death receptors in many cancer cells, the introduction of DR selectivity is thought to create more potent TRAIL agonists with superior therapeutic properties. By use of a computer-aided structure-based design followed by rational combination of mutations, we obtained variants that signal exclusively via DR4. Besides an enhanced selectivity, these TRAIL-DR4 agonists show superior affinity to DR4, and a high apoptosis-inducing activity against several TRAIL-sensitive and -resistant cancer cell lines in vitro. Intriguingly, combined treatment of the DR4-selective variant and a DR5-selective TRAIL variant in cancer cell lines signalling by both death receptors leads to a significant increase in activity when compared with wild-type rhTRAIL or each single rhTRAIL variant. Our results suggest that TRAIL induced apoptosis via high-affinity and rapid-selective homotrimerization of each DR represent an important step towards an efficient cancer treatment.

  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

    2014-08-06

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

  1. Sudden infant death syndrome in Canada: trends in rates and risk factors, 1985-1998.

    Science.gov (United States)

    Rusen, I D; Liu, Shiliang; Sauve, Reg; Joseph, K S; Kramer, Michael S

    2004-01-01

    In Canada, sudden infant death syndrome (SIDS) remains the leading cause of postneonatal death. However, SIDS rates have been declining in many countries, including Canada. This decline has been largely attributed to recommendations to avoid placing infants to sleep in the prone position. We examined the postneonatal rate of mortality due to SIDS and to other causes in relation to the initial risk reduction campaign. The postneonatal mortality rate due to SIDS decreased from 0.97 to 0.54 per 1,000 neonatal survivors between 1985-1989 and 1994-1998 (relative risk [RR] = 0.56, 95% confidence interval [CI] 0.51-0.62). The rate of postneonatal mortality due to other causes also decreased during the same period, though to a smaller extent, from 1.19 to 0.86 (RR = 0.72, 95% CI 0.66-0.78). With the exception of seasonality, established risk factors for SIDS remained essentially unchanged between the two time periods. The observed reduction in postneonatal SIDS is consistent with a positive impact of the initial recommendations regarding risk reduction. However, the lack of reliable risk factor data limits the extent to which the decline can be attributed directly to the campaign.

  2. Predictors of home death among palliative cancer patients in a primary care setting

    DEFF Research Database (Denmark)

    Neergaard, Mette Asbjørn; Olesen, Frede; Vedsted, Peter;

      Background: In most western countries, the majority of palliative cancer patients wish to die at home, where GPs are often deeply involved. However, most research focuses on specialised palliative care, which results in a lack of reliable predictors of home death in primary care. Aim: To analyse...... predictors of home death among deceased palliative cancer patients in a primary care setting. Methods: Using Danish registers, we identified 787 deceased cancer patients and sent a questionnaire to their GPs. The questions concerned the GPs' involvement and the duration of the palliative period at home. We......-of-hours, and whether the GP had had contact with the relatives. Results: 350 questionnaires were filled out. In the preliminary analysis we found that even though many patients died in hospital, this group spent nearly as much of their last time at home as the patients who actually died at home. The analysis...

  3. Galangin induces human colon cancer cell death via the mitochondrial dysfunction and caspase-dependent pathway.

    Science.gov (United States)

    Ha, Tae Kwun; Kim, Mi Eun; Yoon, Ju Hwa; Bae, Sung Jin; Yeom, Jihye; Lee, Jun Sik

    2013-09-01

    Galangin is a member of flavonols and found in Alpinia officinarum, galangal root, and propolis. Previous studies have demonstrated that galangin has anti-cancer effects on several cancers, including melanoma, hepatoma, and leukaemia cells. However, anti-cancer activity of galangin on human colon cancer has not been established yet. In this study, we investigated the anti-cancer effects of galangin on two types of human colon cancer cells (HCT-15 and HT-29). We found that galangin induced apoptosis and DNA condensation of human colon cancer cells in a dose-dependent manner. We also determined that galangin increased the activation of caspase-3 and -9, and release of apoptosis inducing factor from the mitochondria into the cytoplasm by Western blot analysis. In addition, galangin induced human colon cancer cell death through the alteration of mitochondria membrane potential and dysfunction. These results suggest that galangin induces apoptosis of HCT-15 and HT-29 human colon cancer cells and may prove useful in the development of therapeutic agents for human colon cancer.

  4. 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

    2007-01-01

    for 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...... with 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...

  5. 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 ...

  6. 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.

  7. Role of mitochondria-associated hexokinase II in cancer cell death induced by 3-bromopyruvate.

    Science.gov (United States)

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

    2009-05-01

    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 showed that 3-BrPA caused a covalent modification of HKII protein and directly triggered its dissociation from mitochondria, leading to a specific release of apoptosis-inducing factor (AIF) from the mitochondria to cytosol and eventual cell death. Co-immunoprecipitation revealed a physical interaction between HKII and AIF. Using a competitive peptide of HKII, we showed that the dissociation of hexokinase II from mitochondria alone could cause apoptotic cell death, especially in the mitochondria-deficient rho(0) cells that highly express HKII. Interestingly, the dissociation of HKII itself did not directly affect the mitochondrial membrane potential, ROS generation, and oxidative phosphorylation. Our study suggests that the physical association between HKII and AIF is important for the normal localization of AIF in the mitochondria, and disruption of this protein complex by 3-BrPA leads to their release from the mitochondria and eventual cell death.

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

    Directory of Open Access Journals (Sweden)

    Dongjun Luo

    2016-01-01

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

  9. Successful antidepressant treatment for five terminally ill cancer patients with major depression, suicidal ideation and a desire for death.

    Science.gov (United States)

    Kugaya, A; Akechi, T; Nakano, T; Okamura, H; Shima, Y; Uchitomi, Y

    1999-11-01

    In the debate on euthanasia and physician-assisted suicide, we have to exclude terminally ill patients in whom the desire for death is caused by major depression. However, it is still not clear to what degree major depression can be treated by psychiatric intervention in this setting. We evaluated the effect of antidepressant treatment in terminally ill cancer patients. Six cancer patients with suicidal ideas thought to be due to major depression were treated with tricyclic antidepressants. Three had requested terminal sedation to relieve them from their suffering. The median survival of five of these patients was 4 weeks after diagnosis; one was lost to follow-up. The efficacy of the antidepressant treatment was assessed using the Hamilton Rating Scale for Depression (HRSD). One week after the start of treatment with antidepressants, five of the six patients showed a marked improvement in their mood and showed no further suicidal thoughts or requests for terminal sedation. The average reduction in the HRSD score was 23.4 points (14-38; SD = 9. 9). Antidepressant treatment can be effective in alleviating the desire for death due to major depression, even in terminally ill cancer patients.

  10. Rate of change in kidney function and the risk of death: the case for incorporating the rate of kidney function decline into the CKD staging system.

    Science.gov (United States)

    Al-Aly, Ziyad; Cepeda, Oscar

    2011-01-01

    Chronic kidney disease (CKD) is associated with increased risk of death. A wave of recent studies used longitudinal data to examine the effect of the rate of decline of kidney function on the risk of death. The results from these studies show that there is an independent and graded association between the rate of kidney function decline and the risk of death. There is a need to incorporate the rate of decline in the definition of CKD. This redefinition of CKD will transform a static definition into a dynamic one that more accurately describes the disease state in an individual patient.

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

    Science.gov (United States)

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

    2012-11-20

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

  12. Competing risks of death in women treated with adjuvant aromatase inhibitors for early breast cancer on NCIC CTG MA.27.

    Science.gov (United States)

    Chapman, Judith-Anne W; Shepherd, Lois E; Ingle, James N; Muss, Hyman B; Pritchard, Kathleen I; Gelmon, Karen A; Whelan, Timothy J; Elliott, Catherine; Goss, Paul E

    2016-04-01

    Baseline patient and tumor characteristics differentially affected type of death in the MA.17 placebo-controlled letrozole trial where cardiovascular death was not separately identified. The MA.27 trial allowed competing risks analysis of breast cancer (BC), cardiovascular, and other type (OT) of death. MA.27 was a phase III adjuvant breast cancer trial of exemestane versus anastrozole. Effects of baseline patient and tumor characteristics were tested for whether factors were associated with (1) all cause mortality and (2) cause-specific mortality. We also fit step-wise forward cause-specific-adjusted models. 7576 women (median age 64 years; 5417 (72 %) breast cancer related. Baseline patient and tumor characteristics differentially affected type of death with women 70 or older experiencing more non-breast cancer death.

  13. 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;

    2013-01-01

    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...... 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...

  14. 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...

  15. Phenomenology of infant death rates. Identification of the peaks of viral and bacterial diseases

    CERN Document Server

    Richmond, Peter

    2016-01-01

    After birth setting up an effective immune system is a major challenge for all living organisms. In this paper we show that this process can be explored by using the age-specific infant death rate as a kind of sensor. This is made possible because, as shown by the authors in Berrut et al. (2016), between birth and a critical age t_c, for all mammals the death rate decreases with age as an hyperbolic function. For humans t_c is equal to 10 years. At some ages the hyperbolic fall displays spikes which, it is assumed, correspond to specific events in the organism's response to exogenous factors. One of these spikes occurs 10 days after birth and there is another at the age of about 300 days. It is shown that the first spike is related to viral infections whereas the second is related to bacterial diseases. By going back to former time periods during which infant mortality was much higher than currently, it is possible to get a magnified view of these peaks which in turn may give us useful information about how a...

  16. 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.

  17. Mitochondrial Complex I Inhibitors and Forced Oxidative Phosphorylation Synergize in Inducing Cancer Cell Death

    Directory of Open Access Journals (Sweden)

    Roberta Palorini

    2013-01-01

    Full Text Available Cancer cells generally rely mostly on glycolysis rather than oxidative phosphorylation (OXPHOS for ATP production. In fact, they are particularly sensitive to glycolysis inhibition and glucose depletion. On the other hand mitochondrial dysfunctions, involved in the onset of the Warburg effect, are sometimes also associated with the resistance to apoptosis that characterizes cancer cells. Therefore, combined treatments targeting both glycolysis and mitochondria function, exploiting peculiar tumor features, might be lethal for cancer cells. In this study, we show that glucose deprivation and mitochondrial Complex I inhibitors synergize in inducing cancer cell death. In particular, our results reveal that low doses of Complex I inhibitors, ineffective on immortalized cells and in high glucose growth, become specifically cytotoxic on cancer cells deprived of glucose. Importantly, the cytotoxic effect of the inhibitors on cancer cells is strongly enhanced by forskolin, a PKA pathway activator, that we have previously shown to stimulate OXPHOS. Taken together, we demonstrate that induction in cancer cells of a switch from a glycolytic to a more respirative metabolism, obtained by glucose depletion or mitochondrial activity stimulation, strongly increases their sensitivity to low doses of mitochondrial Complex I inhibitors. Our findings might be a valuable approach to eradicate cancer cells.

  18. 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.

  19. Ethanolic Extract of Propolis Augments TRAIL-Induced Apoptotic Death in Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ewelina Szliszka

    2011-01-01

    Full Text Available Prostate cancer is a commonly diagnosed cancer in men. The ethanolic extract of propolis (EEP and its phenolic compounds possess immunomodulatory, chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/APO2L is a naturally occurring anticancer agent that preferentially induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effects of EEP and phenolic compounds isolated from propolis in combination with TRAIL on two prostate cancer cell lines, hormone-sensitivity LNCaP and hormone-refractory DU145. The cytotoxicity was evaluated by MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC/propidium iodide. The prostate cancer cell lines were proved to be resistant to TRAIL-induced apoptosis. Our study demonstrated that EEP and its components significantly sensitize to TRAIL-induced death in prostate cancer cells. The percentage of the apoptotic cells after cotreatment with 50 μg mL−1 EEP and 100 ng mL−1 TRAIL increased to 74.9 ± 0.7% for LNCaP and 57.4 ± 0.7% for DU145 cells. The strongest cytotoxic effect on LNCaP cells was exhibited by apigenin, kaempferid, galangin and caffeic acid phenylethyl ester (CAPE in combination with TRAIL (53.51 ± 0.68–66.06 ± 0.62% death cells. In this work, we showed that EEP markedly augmented TRAIL-mediated apoptosis in prostate cancer cells and suggested the significant role of propolis in chemoprevention of prostate cancer.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Kobori Eiko

    2006-09-01

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

  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....

  4. Calculation of the number of cancer deaths prevented by the Uranium Mill Tailings Remedial Action Project.

    Science.gov (United States)

    Miller, M L; Cornish, R E; Pomatto, C B

    1999-05-01

    The Uranium Mill Tailings Remedial Action Project has completed remedial action at 22 uranium mill tailings sites and about 5,000 properties ("vicinity properties") where tailings were used in construction, at a total cost of $1.45 billion. This paper uses existing data from Environmental Impact Statements and Environmental Assessments, and vicinity property calculations, to determine the total number of cancer deaths averted by the Uranium Mill Tailings Remedial Action Project. The cost-effectiveness of remediating each site, the vicinity properties, and the entire project is calculated. The cost per cancer death averted was four orders of magnitude higher at the least cost-effective site than at the most cost-effective site.

  5. Scaling in Rate-Changeable Birth and Death Processes with Random Removals

    Institute of Scientific and Technical Information of China (English)

    KE Jian-Hong; LIN Zhen-Quan; CHEN Xiao-Shuang

    2009-01-01

    We propose a monomer birth-death model with random removals, in which an aggregate of size k can produce a new monomer at a time-dependent rate I(t)k or lose one monomer at a rate J(t)k, and with a probability P(t) an aggregate of any size is randomly removed. We then analytically investigate the kinetic evolution of the model by means of the rate equation. The results show that the scaling behavior of the aggregate size distribution is dependent crucially on the net birth rate I(t)-J(t) as well as the birth rate I(t). The aggregate size distribution can approach a standard or modified scaling form in some cases, but it may take a scale-free form in other cases. Moreover, the species can survive finally only if either I(t) - J(t) ≥ P(t) or [J(t) + P(t) - I(t)]t (≌) 0 at t > 1; otherwise, it will become extinct.

  6. Factors Associated with Cancer- and Non-Cancer-Related Deaths among Taiwanese Patients with Diabetes after 17 Years of Follow-Up

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2016-01-01

    Objective A previous 12-year follow-up of a large diabetes cohort in Taiwan suggested a survival advantage in the patients with obesity. The present study further investigated additional determinants for cancer and non-cancer death in the cohort after a follow-up of 17 years. Methods A cohort of 92546 diabetes patients recruited since 1995 was followed for vital status by matching the National Death Certificate Database until 2011. Cox regression estimated the hazard ratios for the following variables: age at baseline, sex, diabetes type, screen-detected diabetes (diabetes diagnosed accidentally through epidemiological screening programs or during visits to medical settings without a history of diabetes), diabetes duration, body mass index, insulin use, hypertension, smoking, and living region. Fasting glucose and history of dyslipidemia were available for additional adjustment in a subcohort of the patients (n = 14559). Results A total of 40229 diabetes patients (43.5% of the cohort) died during follow-up and 10.9% died under the age of 60. Insulin use and smoking significantly predicted cancer and non-cancer death. The adjusted hazard ratio (95% confidence interval) associated with insulin use was 1.161 (1.052–1.281) for cancer death and 1.469 (1.413–1.526) for non-cancer death. Screen-detected diabetes and body mass index were consistently associated with a lower risk, but diabetes duration a higher risk, for non-cancer death, with adjusted hazard ratio of 0.683 (0.666–0.702), 0.955 (0.951–0.958) and 1.018 (1.017–1.020), respectively. Diabetes type had a null association disregarding the causes of death and living in rural areas was significantly associated with a higher mortality from non-cancer death. Hypertension, fasting glucose and dyslipidemia showed differential impacts on cancer and non-cancer death, and were significantly predictive for non-cancer death. Conclusions Screen-detected diabetes and a higher body mass index provide a survival

  7. Predictors of early death in female patients with breast cancer in the UK: a cohort study.

    Science.gov (United States)

    Stapelkamp, Ceilidh; Holmberg, Lars; Tataru, Daniela; Møller, Henrik; Robinson, David

    2011-01-01

    Objective To identify factors predicting early death in women with breast cancer. Design Cohort study. Setting 29 trusts across seven cancer networks in the North Thames area. Participants 15 037 women with primary breast cancer diagnosed between January 1996 and December 2005. Methods Logistic regression analyses to determine predictors of early death and factors associated with lack of surgical treatment. Main exposures Age at diagnosis, mode of presentation, ethnicity, disease severity, comorbidities, treatment and period of diagnosis in relation to the Cancer Plan (the NHS's strategy in 2000 for investment in and reform of cancer services). Main outcome measures Death from any cause within 1 year of diagnosis, and receipt of surgical treatment. Results By 31 December 2006, 4765 women had died, 980 in the year after diagnosis. Older age and disease severity independently predicted early death. Women over 80 were more likely to die early than women under 50 (OR 8.05, 95% CI 5.96 to 10.88). Presence of distant metastases on diagnosis increased the odds of early death more than eightfold (OR 8.41, 95% CI 6.49 to 10.89). Two or more recorded comorbidities were associated with a nearly fourfold increase. There was a significant decrease in odds associated with surgery (OR 0.29, 95% CI 0.24 to 0.35). Independently of disease severity and comorbidities, women over 70 were less likely than those under 50 to be treated surgically and this was even more pronounced in those aged over 80 (OR 0.09, 95% CI 0.07 to 0.10). Other factors independently associated with a reduced likelihood of surgery included a non-screening presentation, non-white ethnicity and additional comorbidities. Conclusions These findings may partially explain the survival discrepancies between the UK and other European countries in female patients with breast cancer. The study identifies a group of women with a particularly poor prognosis for whom interventions aiming at early detection may be targeted.

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

    DEFF Research Database (Denmark)

    Hammer, Anne; Rositch, Anne; Kahlert, Johnny Abildgaard;

    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...

  9. Fetal death and reduced birth rates associated with exposure to lead-contaminated drinking water.

    Science.gov (United States)

    Edwards, Marc

    2014-01-01

    This ecologic study notes that fetal death rates (FDR) during the Washington DC drinking water "lead crisis" (2000-2004) peaked in 2001 when water lead levels (WLLs) were highest, and were minimized in 2004 after public health interventions were implemented to protect pregnant women. Changes in the DC FDR vs neighboring Baltimore City were correlated to DC WLL (R(2) = 0.72). Birth rates in DC also increased versus Baltimore City and versus the United States in 2004-2006, when consumers were protected from high WLLs. The increased births in DC neighborhoods comparing 2004 versus 2001 was correlated to the incidence of lead pipes (R(2) = 0.60). DC birth rates from 1999 to 2007 correlated with proxies for maternal blood lead including the geometric mean blood lead in DC children (R(2) = 0.68) and the incidence of lead poisoning in children under age 1.3 years (R(2) = 0.64). After public health protections were removed in 2006, DC FDR spiked in 2007-2009 versus 2004-2006 (p lead service line replacements, and DC FDR dropped to historically low levels in 2010-2011 after consumers were protected and the PSLR program was terminated. Re-evaluation of a historic construction-related miscarriage cluster in the USA Today Building (1987-1988), demonstrates that high WLLs from disturbed plumbing were a possible cause. Overall results are consistent with prior research linking increased lead exposure to higher incidence of miscarriages and fetal death, even at blood lead elevations (≈5 μg/dL) once considered relatively low.

  10. Glucose starvation-mediated inhibition of salinomycin induced autophagy amplifies cancer cell specific cell death.

    Science.gov (United States)

    Jangamreddy, Jaganmohan R; Jain, Mayur V; Hallbeck, Anna-Lotta; Roberg, Karin; Lotfi, Kourosh; Łos, Marek J

    2015-04-30

    Salinomycin has been used as treatment for malignant tumors in a small number of humans, causing far less side effects than standard chemotherapy. Several studies show that Salinomycin targets cancer-initiating cells (cancer stem cells, or CSC) resistant to conventional therapies. Numerous studies show that Salinomycin not only reduces tumor volume, but also decreases tumor recurrence when used as an adjuvant to standard treatments. In this study we show that starvation triggered different stress responses in cancer cells and primary normal cells, which further improved the preferential targeting of cancer cells by Salinomycin. Our in vitro studies further demonstrate that the combined use of 2-Fluoro 2-deoxy D-glucose, or 2-deoxy D-glucose with Salinomycin is lethal in cancer cells while the use of Oxamate does not improve cell death-inducing properties of Salinomycin. Furthermore, we show that treatment of cancer cells with Salinomycin under starvation conditions not only increases the apoptotic caspase activity, but also diminishes the protective autophagy normally triggered by the treatment with Salinomycin alone. Thus, this study underlines the potential use of Salinomycin as a cancer treatment, possibly in combination with short-term starvation or starvation-mimicking pharmacologic intervention.

  11. Cell death associated with abnormal mitosis observed by confocal imaging in live cancer cells.

    Science.gov (United States)

    Castiel, Asher; Visochek, Leonid; Mittelman, Leonid; Zilberstein, Yael; Dantzer, Francoise; Izraeli, Shai; Cohen-Armon, Malka

    2013-08-21

    Phenanthrene derivatives acting as potent PARP1 inhibitors prevented the bi-focal clustering of supernumerary centrosomes in multi-centrosomal human cancer cells in mitosis. The phenanthridine PJ-34 was the most potent molecule. Declustering of extra-centrosomes causes mitotic failure and cell death in multi-centrosomal cells. Most solid human cancers have high occurrence of extra-centrosomes. The activity of PJ-34 was documented in real-time by confocal imaging of live human breast cancer MDA-MB-231 cells transfected with vectors encoding for fluorescent γ-tubulin, which is highly abundant in the centrosomes and for fluorescent histone H2b present in the chromosomes. Aberrant chromosomes arrangements and de-clustered γ-tubulin foci representing declustered centrosomes were detected in the transfected MDA-MB-231 cells after treatment with PJ-34. Un-clustered extra-centrosomes in the two spindle poles preceded their cell death. These results linked for the first time the recently detected exclusive cytotoxic activity of PJ-34 in human cancer cells with extra-centrosomes de-clustering in mitosis, and mitotic failure leading to cell death. According to previous findings observed by confocal imaging of fixed cells, PJ-34 exclusively eradicated cancer cells with multi-centrosomes without impairing normal cells undergoing mitosis with two centrosomes and bi-focal spindles. This cytotoxic activity of PJ-34 was not shared by other potent PARP1 inhibitors, and was observed in PARP1 deficient MEF harboring extracentrosomes, suggesting its independency of PARP1 inhibition. Live confocal imaging offered a useful tool for identifying new molecules eradicating cells during mitosis.

  12. Liver protects metastatic prostate cancer from induced death by activating E-cadherin signaling.

    Science.gov (United States)

    Ma, Bo; Wheeler, Sarah E; Clark, Amanda M; Whaley, Diana L; Yang, Min; Wells, Alan

    2016-11-01

    Liver is one of the most common sites of cancer metastasis. Once disseminated, the prognosis is poor as these tumors often display generalized chemoresistance, particularly for carcinomas that derive not from the aerodigestive tract. When these cancers seed the liver, the aggressive cells usually undergo a mesenchymal to epithelial reverting transition that both aids colonization and renders the tumor cells chemoresistant. In vitro studies demonstrate that hepatocytes drive this phenotypic shift. However, the in vivo evidence and the molecular signals that protect these cells from induced death are yet to be defined. Herein, we report that membrane surface E-cadherin-expressing prostate cancer cells were resistant to cell death by chemotherapeutic drugs but E-cadherin null cells or those expressing E-cadherin only in the cytoplasm were sensitive to death signals and chemotherapies both in vitro and in vivo. While cell-cell E-cadherin ligandation reduced mitogenesis, this chemoprotection was proliferation-independent as killing of both 5-ethynyl-2'-deoxyuridine-positive (or Ki67(+) ) and 5-ethynyl-2'-deoxyuridine-negative (Ki67(-) ) cells was inversely related to membrane-bound E-cadherin. Inhibiting the canonical survival kinases extracellular signal-regulated protein kinases, protein kinase B, and Janus kinase, which are activated by chemotherapeutics in epithelial cell-transitioned prostate cancer, abrogated the chemoresistance both in cell culture and in animal models of metastatic cancer. For disseminated tumors, protein kinase B disruption in itself had no effect on tumor survival but was synergistic with chemotherapy, leading to increased killing.

  13. Heart rate turbulence to guide treatment for prevention of sudden death.

    Science.gov (United States)

    Bauer, Axel; Zürn, Christine S; Schmidt, Georg

    2010-06-01

    Heart rate turbulence (HRT) denotes the baroreflex-mediated short-term oscillation of cardiac cycle lengths after spontaneous ventricular premature complexes. The physiological pattern of HRT consists of brief heart rate acceleration followed by more gradual heart rate deceleration before the heart rate returns to baseline. Physiological mechanisms of HRT are complex and require an intact interplay between both sympathetic and parasympathetic nervous systems. The strong and independent prognostic value of HRT in identifying postinfarction patients at high risk for death has been validated in six retrospective and three prospective studies together enrolling more than 8000 patients. This evidence qualifies HRT as a promising tool for selection of patients who might benefit from implantation of a cardioverter-defibrillator. Moreover, HRT predicts poor outcome in patients with heart failure. It is not only correlated with a patient's clinical status, but also recovers when heart failure treatment, including beta-blockers, angiotensin-converting enzyme inhibitors, or cardiac resynchronization therapy, is effective. Therefore, HRT might also be used as a treatment target to guide pharmacotherapy of heart failure.

  14. 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

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

    NARCIS (Netherlands)

    M.J. 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 u

  16. Phenethyl isothiocyanate upregulates death receptors 4 and 5 and inhibits proliferation in human cancer stem-like cells

    OpenAIRE

    Wang, Dan; Upadhyaya, Bijaya; Liu, Yi; Knudsen, David; Dey, Moul

    2014-01-01

    Background The cytokine TRAIL (tumor necrotic factor-related apoptosis-inducing ligand) selectively induces apoptosis in cancer cells, but cancer stem cells (CSCs) that contribute to cancer-recurrence are frequently TRAIL-resistant. Here we examined hitherto unknown effects of the dietary anti-carcinogenic compound phenethyl isothiocyanate (PEITC) on attenuation of proliferation and tumorigenicity and on up regulation of death receptors and apoptosis in human cervical CSC. Methods Cancer stem...

  17. Trends in lung cancer incidence rates, Oklahoma 2005-2010.

    Directory of Open Access Journals (Sweden)

    Dana S Mowls

    Full Text Available 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.Data on Oklahoma's incident cases of lung cancer (2005-2010 were obtained from the Centers for Disease Control and Prevention WONDER system. Annual percent change (APC was calculated by linear regression to characterize trends in lung cancer incidence rates over time for the overall population, by gender, by age group, and by age group within gender. Rates were considered to increase or decrease if the p-value for trend was <0.05.From 2005 through 2010, lung cancer incidence rates declined from 81.96 to 68.19 per 100,000 population, with an APC of -3.58% (p-value: 0.0220. When subgroups were examined, declines were observed among all males (APC: -4.25%; p-value: 0.0270, males <65 years (APC: -5.32%; p-value: 0.0008, females <65 years (APC: -4.85%; p-value: 0.0044, and persons aged 55-64 years (APC: -6.38%; p-value: 0.0017.Declines in lung cancer incidence rates occurred during 2005-2010 among the overall population and within select demographic groups in Oklahoma. Although trends were stable for several demographic groups, rates of lung cancer incidence were lower in 2010 compared to 2005. Continued evidence-based tobacco control efforts are needed to ensure further reductions in lung cancer incidence rates in the state of Oklahoma.

  18. Relations between desire for early death, depressive symptoms and antidepressant prescribing in terminally ill patients with cancer.

    Science.gov (United States)

    Tiernan, E; Casey, P; O'Boyle, C; Birkbeck, G; Mangan, M; O'Siorain, L; Kearney, M

    2002-08-01

    Some patients with advanced cancer express the wish for an early death. This may be associated with depression. We examined the relations between depressive symptoms and desire for early death (natural or by euthanasia or physician-assisted suicide) in 142 terminally ill patients with cancer being cared for by a specialist palliative care team. They completed the Hospital Anxiety and Depression Scale questionnaire and answered four supplementary questions on desire for early death. Only 2 patients expressed a strong wish for death by some form of suicide or euthanasia. 120 denied that they ever wished for early release. The desire for early death correlated with depression scores. Depressive symptoms were common in the whole group but few were on antidepressant therapy. Better recognition and treatment of depression might improve the lives of people with terminal illness and so lessen desire for early death, whether natural or by suicide.

  19. Exercise Rates Often Decline After Cancer Diagnosis

    Science.gov (United States)

    ... There need to be more exercise programs within health centers and in gyms to provide cancer patients with guidance to help ... their loved ones by joining them at the gym, on walks or in fitness classes," she ... mood and improve sleep," Heller said. The study included about 660 ...

  20. The alpha1-adrenoceptor antagonist terazosin induces prostate cancer cell death through a p53 and Rb independent pathway.

    Science.gov (United States)

    Xu, Kexin; Wang, Xianghong; Ling, Patrick M T; Tsao, S W; Wong, Y C

    2003-01-01

    Prostate cancer is the second leading cause of cancer-related death in men. Treatment failure in prostate cancer is usually due to the development of androgen independence and resistance to chemotherapeutic drugs at an advanced stage. Recently, it was reported that the alpha1-adrenoceptor antagonist terazosin was able to inhibit prostate cancer cell growth and indicated that it may have an implication in the treatment of prostate cancer. The aim of the present study was to investigate the mechanisms involved in terazosin-induced prostate cancer cell death using two androgen-independent cell lines, PC-3 and DU145. Our results showed that terazosin inhibited not only prostate cancer cell growth but also colony forming ability, which is the main target of chemotherapy. We also found that the sensitivity of these cells to terazosin was not affected by the presence of either functional p53 or Rb, suggesting that the terazosin-induced cell death was independent of p53 and Rb. However, the terazosin-induced cell death was associated with G1 phase cell cycle arrest and up-regulation of p27KIP1. In addition, up-regulation of Bax and down-regulation of Bcl-2 was also observed indicating that these two apoptotic regulators may play important roles in terazosin-mediated cell death pathway. Our results provide evidence for the first time that terazosin may have a therapeutic potential in the treatment of advanced prostate cancer.

  1. Selenium Compounds, Apoptosis and Other Types of Cell Death: An Overview for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Juan Antonio Palop

    2012-08-01

    Full Text Available Selenium (Se is an essential trace element involved in different physiological functions of the human body and plays a role in cancer prevention and treatment. Induction of apoptosis is considered an important cellular event that can account for the cancer preventive effects of Se. The mechanisms of Se-induced apoptosis are associated with the chemical forms of Se and their metabolism as well as the type of cancer studied. So, some selenocompounds, such as SeO2 involve the activation of caspase-3 while sodium selenite induces apoptosis in the absence of the activation of caspases. Modulation of mitochondrial functions has been reported to play a key role in the regulation of apoptosis and also to be one of the targets of Se compounds. Other mechanisms for apoptosis induction are the modulation of glutathione and reactive oxygen species levels, which may function as intracellular messengers to regulate signaling pathways, or the regulation of kinase, among others. Emerging evidence indicates the overlaps between the apoptosis and other types of cell death such as autophagy. In this review we report different processes of cell death induced by Se compounds in cancer treatment and prevention.

  2. Investigating the cell death mechanisms in primary prostate cancer cells using low-temperature plasma treatment

    Science.gov (United States)

    O'Connell, Deborah; Hirst, A. M.; Packer, J. R.; Simms, M. S.; Mann, V. M.; Frame, F. M.; Maitland, N. J.

    2016-09-01

    Atmospheric pressure plasmas have shown considerable promise as a potential cancer therapy. An atmospheric pressure plasma driven with kHz kV excitation, operated with helium and oxygen admixtures is used to investigate the interaction with prostate cancer cells. The cytopathic effect was verified first in two commonly used prostate cancer cell lines (BPH-1 and PC-3 cells) and further extended to examine the effects in paired normal and tumour prostate epithelial cells cultured directly from patient tissues. Through the formation of reactive species in cell culture media, and potentially other plasma components, we observed high levels of DNA damage, together with reduced cell viability and colony-forming ability. We observed differences in response between the prostate cell lines and primary cells, particularly in terms of the mechanism of cell death. The primary cells ultimately undergo necrotic cell death in both the normal and tumour samples, in the complete absence of apoptosis. In addition, we provide the first evidence of an autophagic response in primary cells. This work highlights the importance of studying primary cultures in order to gain a more realistic insight into patient efficacy. EPSRC EP/H003797/1 & EP/K018388/1, Yorkshire Cancer Research: YCR Y257PA.

  3. 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.

  4. Relations between desire for early death, depressive symptoms and antidepressant prescribing in terminally ill patients with cancer

    OpenAIRE

    Tiernan, E; Casey, P; O'Boyle, C; Birkbeck, G; Mangan, M; O'Siorain, L; Kearney, M.

    2002-01-01

    Some patients with advanced cancer express the wish for an early death. This may be associated with depression. We examined the relations between depressive symptoms and desire for early death (natural or by euthanasia or physician-assisted suicide) in 142 terminally ill patients with cancer being cared for by a specialist palliative care team. They completed the Hospital Anxiety and Depression Scale questionnaire and answered four supplementary questions on desire for...

  5. Autophagy-related cell death by pan-histone deacetylase inhibition in liver cancer

    Science.gov (United States)

    Di Fazio, Pietro; Waldegger, Petra; Jabari, Samir; Lingelbach, Susanne; Montalbano, Roberta; Ocker, Matthias; Slater, Emily P.; Bartsch, Detlef K.; Illig, Romana; Neureiter, Daniel; Wissniowski, Thaddeus T.

    2016-01-01

    Autophagy is a homeostatic, catabolic degradation process and cell fate essential regulatory mechanism. Protracted autophagy triggers cell death; its aberrant function is responsible for several malignancies. Panobinostat, a potent pan-deacetylase inhibitor, causes endoplasmic reticulum stress-induced cell death. The aim of this study was to investigate the role of autophagy in deacetylase inhibitor-triggered liver cancer cell death. HepG2 (p53wt) and Hep3B (p53 null) liver cancer cell lines were exposed to panobinostat. RT-qPCR and western blot confirmed autophagic factor modulation. Immuno-fluorescence, -precipitation and -histochemistry as well as transmission electron microscopy verified autophagosome formation. The cytotoxicity of panobinostat and autophagy modulators was detected using a real time cell viability assay. Panobinostat induced autophagy-related factor expression and aggregation. Map1LC3B and Beclin1 were significantly over-expressed in HepG2 xenografts in nude mice treated with panobinostat for 4 weeks. Subcellular distribution of Beclin1 increased with the appearance of autophagosomes-like aggregates. Cytosolic loss of p53, in HepG2, and p73, in Hep3B cells, and a corresponding gain of their nuclear level, together with modulation of DRAM1, were observed. Autophagosome aggregation was visible after 6 h of treatment. Treatment of cells stably expressing GFP-RFPtag Map1LC3B resulted in aggregation and a fluorescence switch, thus confirming autophagosome formation and maturation. Tamoxifen, an inducer of autophagy, caused only a block in cell proliferation; but in combination with panobinostat it resulted in cell death. Autophagy triggers cell demise in liver cancer. Its modulation by the combination of tamoxifen and panobinostat could be a new option for palliative treatment of hepatocellular carcinoma. PMID:27058414

  6. Discovery of Small Molecules That Induce Lysosomal Cell Death in Cancer Cell Lines Using an Image-Based Screening Platform

    NARCIS (Netherlands)

    Pagliero, Romina J; D'Astolfo, Diego S; Lelieveld, Daphne; Pratiwi, Riyona D; Aits, Sonja; Jaattela, Marja; Martin, Nathaniel I; Klumperman, Judith; Egan, David A

    2016-01-01

    The lysosomal cell death (LCD) pathway is a caspase 3-independent cell death pathway that has been suggested as a possible target for cancer therapy, making the development of sensitive and specific high-throughput (HT) assays to identify LCD inducers highly desirable. In this study, we report a two

  7. killerFLIP: a novel lytic peptide specifically inducing cancer cell death.

    Science.gov (United States)

    Pennarun, B; Gaidos, G; Bucur, O; Tinari, A; Rupasinghe, C; Jin, T; Dewar, R; Song, K; Santos, M T; Malorni, W; Mierke, D; Khosravi-Far, R

    2013-10-31

    One of the objectives in the development of effective cancer therapy is induction of tumor-selective cell death. Toward this end, we have identified a small peptide that, when introduced into cells via a TAT cell-delivery system, shows a remarkably potent cytoxicity in a variety of cancer cell lines and inhibits tumor growth in vivo, whereas sparing normal cells and tissues. This fusion peptide was named killerFLIP as its sequence was derived from the C-terminal domain of c-FLIP, an anti-apoptotic protein. Using structure activity analysis, we determined the minimal bioactive core of killerFLIP, namely killerFLIP-E. Structural analysis of cells using electron microscopy demonstrated that killerFLIP-E triggers cell death accompanied by rapid (within minutes) plasma membrane permeabilization. Studies of the structure of the active core of killerFLIP (-E) indicated that it possesses amphiphilic properties and self-assembles into micellar structures in aqueous solution. The biochemical properties of killerFLIP are comparable to those of cationic lytic peptides, which participate in defense against pathogens and have also demonstrated anticancer properties. We show that the pro-cell death effects of killerFLIP are independent of its sequence similarity with c-FLIPL as killerFLIP-induced cell death was largely apoptosis and necroptosis independent. A killerFLIP-E variant containing a scrambled c-FLIPL motif indeed induced similar cell death, suggesting the importance of the c-FLIPL residues but not of their sequence. Thus, we report the discovery of a promising synthetic peptide with novel anticancer activity in vitro and in vivo.

  8. Low Programmed Cell Death 5 Expression is a Prognostic Factor in Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    Li Gao; Xue Ye; Rui-Qiong Ma; Hong-Yan Cheng; Hong-Jing Han; Heng Cui; Li-Hui Wei

    2015-01-01

    Background:Ovarian cancer is a leading gynecological malignancy.We investigated the prognostic value of programmed cell death 5 (PDCD5) in patients with ovarian cancer.Methods:Expression levels ofPDCD5 mRNA and protein were examined in six ovarian cancer cell lines (SKOV3,CAOV3,ES2,OV1,3AO,and HOC1A) and one normal ovarian epithelial cell line (T29) using reverse transcription polymerase chain reaction,Westem blotting,and flow cytometry.After inducing PDCD5 induction in SKOV3 cells or treating this cell line with taxol or doxorubicin (either alone or combined),apoptosis was measured by Annexin V-FITC/propidium iodide staining.Correlations between PDCD5 protein expression and pathological features,histological grade,FIGO stage,effective cytoreductive surgery,and serum cancer antigen-125 values were evaluated in patients with ovarian cancer.Results:PDCD5 mRNA and protein expression were downregulated in ovarian cancer cells.Recombinant human PDCD5 increased doxorubicin-induced apoptosis in SKOV3 cells (15.96 ± 2.07%,vs.3.17 ± 1.45% in controls).In patients with ovarian cancer,PDCD5 expression was inversely correlated with FIGO stage,pathological grade,and patient survival (P < 0.05,R =0.7139 for survival).Conclusions:PDCD5 expression is negatively correlated with disease progression and stage in ovarian cancer.Therefore,measuring PDCD5 expression may be a good method of determining the prognosis of ovarian cancer patients.

  9. Death receptor 5 expression is inversely correlated with prostate cancer progression

    Science.gov (United States)

    HERNANDEZ-CUETO, ANGELES; HERNANDEZ-CUETO, DANIEL; ANTONIO-ANDRES, GABRIELA; MENDOZA-MARIN, MARISELA; JIMENEZ-GUTIERREZ, CARLOS; SANDOVAL-MEJIA, ANA LILIA; MORA-CAMPOS, ROSARIO; GONZALEZ-BONILLA, CESAR; VEGA, MARIO I.; BONAVIDA, BENJAMIN; HUERTA-YEPEZ, SARA

    2014-01-01

    Prostate carcinoma (PCa) is one of the most common cancers in men. Prostate-specific antigen (PSA) has been widely used to predict the outcome of PCa and screening with PSA has resulted in a decline in mortality. However, PSA is not an optimal prognostic tool as its sensitivity may be too low to reduce morbidity and mortality. Consequently, there is a demand for additional robust biomarkers for prostate cancer. Death receptor 5 (DR5) has been implicated in the prognosis of several cancers and it has been previously shown that it is negatively regulated by Yin Yang 1 (YY1) in prostate cancer cell lines. The present study investigated the clinical significance of DR5 expression in a prostate cancer patient cohort and its correlation with YY1 expression. Immunohistochemical analysis of protein expression distribution was performed using tissue microarray constructs from 54 primary PCa and 39 prostatic intraepithelial neoplasia (PIN) specimens. DR5 expression was dramatically reduced as a function of higher tumor grade. By contrast, YY1 expression was elevated in PCa tumors as compared with that in PIN, and was increased with higher tumor grade. DR5 had an inverse correlation with YY1 expression. Bioinformatic analyses corroborated these data. The present findings suggested that DR5 and YY1 expression levels may serve as progression biomarkers for prostate cancer. PMID:25174820

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

    Science.gov (United States)

    Curry, Merril C; Peters, Amelia A; Kenny, Paraic A; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2013-05-10

    The mitochondrial calcium uniporter (MCU) transports free ionic Ca(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(2+) levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca(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.

  12. Cancer Rates by Race/Ethnicity and Sex

    Science.gov (United States)

    ... Skin Uterine Cancer Rates by Race/Ethnicity and Sex Language: English Español (Spanish) Recommend on Facebook Tweet ... and ethnicity. Incidence Rates by Race/Ethnicity and Sex “Incidence rate” means how many people out ...

  13. 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 Super Bowl-related days during the winning 1984 game were associated with a lower rate of all-cause death (2.1870 vs 2.3205 for control days, p = 0.0302). In conclusion, the emotional stress of loss and/or the 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.

  14. 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.

  15. 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 ...

  16. Dandelion root extract affects colorectal cancer proliferation and survival through the activation of multiple death signalling pathways.

    Science.gov (United States)

    Ovadje, Pamela; Ammar, Saleem; Guerrero, Jose-Antonio; Arnason, John Thor; Pandey, Siyaram

    2016-11-08

    Dandelion extracts have been studied extensively in recent years for its anti-depressant and anti-inflammatory activity. Recent work from our lab, with in-vitro systems, shows the anti-cancer potential of an aqueous dandelion root extract (DRE) in several cancer cell models, with no toxicity to non-cancer cells. In this study, we examined the cancer cell-killing effectiveness of an aqueous DRE in colon cancer cell models. Aqueous DRE induced programmed cell death (PCD) selectively in > 95% of colon cancer cells, irrespective of their p53 status, by 48 hours of treatment. The anti-cancer efficacy of this extract was confirmed in in-vivo studies, as the oral administration of DRE retarded the growth of human colon xenograft models by more than 90%. We found the activation of multiple death pathways in cancer cells by DRE treatment, as revealed by gene expression analyses showing the expression of genes implicated in programmed cell death. Phytochemical analyses of the extract showed complex multi-component composition of the DRE, including some known bioactive phytochemicals such as α-amyrin, β-amyrin, lupeol and taraxasterol. This suggested that this natural extract could engage and effectively target multiple vulnerabilities of cancer cells. Therefore, DRE could be a non-toxic and effective anti-cancer alternative, instrumental for reducing the occurrence of cancer cells drug-resistance.

  17. 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.

  18. Calprotectin induces cell death in human prostate cancer cell (LNCaP) through survivin protein alteration.

    Science.gov (United States)

    Sattari, Mina; Pazhang, Yaghub; Imani, Mehdi

    2014-11-01

    Calprotectin (CP), an abundant heterodimeric cytosolic protein of neutrophils, conveys a variety of functions such as tumor cell growth arrest and antimicrobial activity. We investigated CP activity and its possible apoptosis-inducing mechanism of action against an antiandrogen therapy-resistance prostate cancer cell line LNCaP. Cell viability and Annexin V FITC assays were performed in order to investigate its cell death activity and apoptosis, respectively. In order to address cell death inducing mechanism(s), immunocytochemistry and immunobloting analysis, reactive oxygen species (ROS) and nitric oxide (NO) measurements were performed. The effective concentration of CP against LNCaP promoting LNCaP cell death was 200 µg/mL. ROS and NO levels of cells remarkably were enhanced following treatment with 50 and 100 µg/mL of CP, respectively. Protein expression of anti-apoptotic protein survivin was significantly decreased after administration of tumor cells with CP. Our data indicate that CP regulates the LNCaP cells viability via survivin-mediated pathway and ROS and NO enhancement. Thus, inhibition of survivin expression, enhancement of ROS and NO level by CP or other similar pharmaceutical agents might be effective in lowering the malignant proliferation of human prostate cancer cells.

  19. National Cancer Institute News

    Science.gov (United States)

    ... life among African-American cancer survivors. Study finds premature death rates diverge in the United States by race and ethnicity January 25, 2017 Premature death rates declined among Hispanics, blacks, and Asian/Pacific ...

  20. From nature to bedside: pro-survival and cell death mechanisms as therapeutic targets in cancer treatment.

    Science.gov (United States)

    Cerella, Claudia; Teiten, Marie-Hélène; Radogna, Flavia; Dicato, Mario; Diederich, Marc

    2014-11-01

    Cell death is an important physiological regulator during development, tissue homeostasis and stress response but it is also a protective tumor suppressive mechanism. Tumor cells almost universally acquire the ability to evade cell death pathways that in normal cells act as a protective mechanism to remove damaged cells. As a result, a population of death-resistant cells with accumulating genetic and epigenetic abnormalities contributes to malignant transformation. Any alteration of the homeostatic balance between survival and death is therefore a critical factor in carcinogenesis. Several forms of cell death exist and cross talk among them is emerging; however, we still miss many molecular details. It becomes essential to revisit the role of each type of cell death to understand interconnections existing between different cell death pathways as well as the network of their mediators to eventually develop new effective strategies to kill cancer cells. More specifically, new therapies based on compounds selectively triggering apoptosis, necrosis or autophagy recently became both appealing and challenging. Despite the rather clear classification of the different cell death modalities according to morphological criteria and the attempt to describe them with distinct signaling pathways, the reality reveals a complex interplay between apoptosis, regulated necrosis and autophagy involving a heterogeneous mix of molecular mediators. Nature, presenting an almost endless plenitude of bioactive scaffolds, can efficiently contribute compounds that allow deciphering the intricate pathways of cell death pathways and thus eventually contribute to selectively target cancer-type specific pathways in an attempt to personalize cancer patient treatment depending on cancer death pathway specificities. The aim of this review is to provide first an overview of molecular cell death specificities and to highlight how compounds of natural origins, with or without hemisynthetic

  1. Prediction of road traffic death rate using neural networks optimised by genetic algorithm.

    Science.gov (United States)

    Jafari, Seyed Ali; Jahandideh, Sepideh; Jahandideh, Mina; Asadabadi, Ebrahim Barzegari

    2015-01-01

    Road traffic injuries (RTIs) are realised as a main cause of public health problems at global, regional and national levels. Therefore, prediction of road traffic death rate will be helpful in its management. Based on this fact, we used an artificial neural network model optimised through Genetic algorithm to predict mortality. In this study, a five-fold cross-validation procedure on a data set containing total of 178 countries was used to verify the performance of models. The best-fit model was selected according to the root mean square errors (RMSE). Genetic algorithm, as a powerful model which has not been introduced in prediction of mortality to this extent in previous studies, showed high performance. The lowest RMSE obtained was 0.0808. Such satisfactory results could be attributed to the use of Genetic algorithm as a powerful optimiser which selects the best input feature set to be fed into the neural networks. Seven factors have been known as the most effective factors on the road traffic mortality rate by high accuracy. The gained results displayed that our model is very promising and may play a useful role in developing a better method for assessing the influence of road traffic mortality risk factors.

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

    Science.gov (United States)

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

    2013-01-01

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

  3. Prediction of Trend between Water Environment Pollution of D Lake and Death Rate of Malignancy in Population

    Institute of Scientific and Technical Information of China (English)

    李龙; 吴春松

    2003-01-01

    Grey system analysis method was used to study the correlation between water pollution in D Lake area and death rate of malignancy with death rate of malignancy as effect sequence and a variety of water pollution index as factor sequence. On the basis of grey correlation analysis, grey system predication model was established for death rate of malignancy in population in D Lake area including GM(1.N) model for death rate of malignancy [ MR(t+1) = (9.9987E1 ± 5. 0001E2 + 10.8994E3+1. 1114E4+165.1029) · e-0.0070t -9. 9987E1 - 5. 0001E2 - 10. 8994E3 - 1. 1114E4] and GM(1,1) model for related factors [ E1(t+1) =52. 1214-46. 9468e -0. 0058t, E2(t+1)=4. 6114-4.5664e0.0015t, E3(t+1)=1.1389-1. 1212e0.0065t, E4(t+1 = 554. 5867-549. 8006e0.0016t], and the trend of death rate of malignancy from 2000 to 2010 was predicted.

  4. Oxidative pentose phosphate pathway inhibition is a key determinant of antimalarial induced cancer cell death.

    Science.gov (United States)

    Salas, E; Roy, S; Marsh, T; Rubin, B; Debnath, J

    2016-06-01

    Despite immense interest in using antimalarials as autophagy inhibitors to treat cancer, it remains unclear whether these agents act predominantly via autophagy inhibition or whether other pathways direct their anti-cancer properties. By comparing the treatment effects of the antimalarials chloroquine (CQ) and quinacrine (Q) on KRAS mutant lung cancer cells, we demonstrate that inhibition of the oxidative arm of the pentose phosphate pathway (oxPPP) is required for antimalarial induced apoptosis. Despite inhibiting autophagy, neither CQ treatment nor RNAi against autophagy regulators (ATGs) promote cell death. In contrast, Q triggers high levels of apoptosis, both in vitro and in vivo, and this phenotype requires both autophagy inhibition and p53-dependent inhibition of the oxPPP. Simultaneous genetic targeting of the oxPPP and autophagy is sufficient to trigger apoptosis in lung cancer cells, including cells lacking p53. Thus, in addition to reduced autophagy, oxPPP inhibition serves as an important determinant of antimalarial cytotoxicity in cancer cells.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  6. Statins Inhibit the Proliferation and Induce Cell Death of Human Papilloma Virus Positive and Negative Cervical Cancer Cells

    OpenAIRE

    Crescencio, María Elena; Rodríguez, Emma; Páez, Araceli; Masso, Felipe A.; Montaño, Luis F.; López-Marure, Rebeca

    2009-01-01

    Statins, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have anti-tumoral effects on multiple cancer types; however, little is known about their effect on cervical cancer. We evaluated the effect on proliferation, cell cycle, oxidative stress and cell death of three statins on CaSki, HeLa (HPV+) and ViBo (HPV−) cervical cancer cell lines. Cell proliferation was assayed by crystal violet staining, cell cycle by flow cytometry and cell death by annexin-V st...

  7. 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…

  8. Novel analogue of colchicine induces selective pro-death autophagy and necrosis in human cancer cells.

    Directory of Open Access Journals (Sweden)

    Kristen Larocque

    Full Text Available Colchicine, a natural product of Colchicum autumnae currently used for gout treatment, is a tubulin targeting compound which inhibits microtubule formation by targeting fast dividing cells. This tubulin-targeting property has lead researchers to investigate the potential of colchicine and analogs as possible cancer therapies. One major study conducted on an analogue of allocolchicine, ZD 6126, was halted in phase 2 clinical trials due to severe cardio-toxicity associated with treatment. This study involves the development and testing of novel allocolchicine analogues that hold non-toxic anti-cancer properties. Currently we have synthesized and evaluated the anti-cancer activities of two analogues; N-acetyl-O-methylcolchinol (NSC 51046 or NCME, which is structurally similar to ZD 6126, and (S-3,8,9,10-tetramethoxyallocolchicine (Green 1, which is a novel derivative of allocolchicine that is isomeric in the A ring. NSC 51046 was found to be non-selective as it induced apoptosis in both BxPC-3 and PANC-1 pancreatic cancer cells and in normal human fibroblasts. Interestingly, we found that Green 1 was able to modestly induce pro-death autophagy in these pancreatic cancer cells and E6-1 leukemia cells but not in normal human fibroblasts. Unlike colchicine and NSC 51046, Green 1 does not appear to affect tubulin polymerization indicating that it has a different molecular target. Green 1 also caused increased reactive oxygen species (ROS production in mitochondria isolated from pancreatic cancer cells. Furthermore, in vivo studies revealed that Green 1 was well tolerated in mice. Our findings suggest that a small change in the structure of colchicine has apparently changed the mechanism of action and lead to improved selectivity. This may lead to better selective treatments in cancer therapy.

  9. 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

    and predictor of outcome in adjuvant chemotherapy‐treated patients with primary breast cancer. These data suggest that the induction of LAMP2‐dependent autophagic flux through CERT targeting may provide a rational approach to enhance multidrug sensitization and potentiate the death of polyploid cells following...... to the death of CIN cancer cells. Using an integrative functional genomics approach, we find that CERT‐specific multidrug sensitization is associated with enhanced autophagosome–lysosome flux, resulting from the expression of LAMP2 following CERT silencing in colorectal and HER2+ breast cancer cell lines. 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 variable...

  10. 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...

  11. A matter of balance between life and death: targeting reactive oxygen species (ROS)-induced autophagy for cancer therapy.

    Science.gov (United States)

    Gibson, Spencer B

    2010-10-01

    Reactive oxygen species (ROS) have been implicated in many biological functions and diseases. Often their role is counterintuitive, where ROS can either promote cell survival or cell death depending on the cellular context. Similarly, autophagy is involved in many biological functions and diseases where it can either promote cell survival or cell death. There is now a growing consensus that ROS controls autophagy in multiple contexts and cell types. Furthermore, alterations in ROS and autophagy regulation contribute to cancer initiation and progression. However, how ROS and autophagy contribute to cancer and how to target either for cancer treatment is controversial. Blocking ROS generation could prevent cancer initiation, whereas blockage of autophagy seems to be required for initiation of cancer. In cancer progression, high levels of ROS correspond with increased metabolism and under metabolic stress autophagy is required to maintain cellular integrity. In cancer treatment, therapeutic drugs that increase ROS and autophagy have been implicated in their mechanism for cell death, such as 2-methoxyestrodial (2-ME) and arsenic trioxide (As(2)O(3)), whereas other therapeutic drugs that induce ROS and autophagy seem to have a protective effect. This has led to different approaches to treat cancer patients where autophagy is either activated or inhibited. Both views of ROS and autophagy are valid and reflect the balance within a cell to either survive or die. Understanding this balancing act within a cell is essential to determine whether to block or activate ROS-controlled autophagy for cancer therapy.

  12. Targeting death receptor TRAIL-R2 by chalcones for TRAIL-induced apoptosis in cancer cells.

    Science.gov (United States)

    Szliszka, Ewelina; Jaworska, Dagmara; Ksek, Małgorzata; Czuba, Zenon P; Król, Wojciech

    2012-11-20

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells without toxicity to normal cells. TRAIL binds to death receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5) expressed on cancer cell surface and activates apoptotic pathways. Endogenous TRAIL plays an important role in immune surveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL mediated death, it is important to search for and develop new strategies to overcome this resistance. Chalcones can sensitize cancer cells to TRAIL-induced apoptosis. We examined the cytotoxic and apoptotic effects of TRAIL in combination with four chalcones: chalcone, isobavachalcone, licochalcone A and xanthohumol on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining by flow cytometry and fluorescence microscopy. Death receptor expression was analyzed using flow cytometry. The decreased expression of death receptors in cancer cells may be the cause of TRAIL-resistance. Chalcones enhance TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2. Our study has indicated that chalcones augment the antitumor activity of TRAIL and confirm their cancer chemopreventive properties.

  13. Targeting Death Receptor TRAIL-R2 by Chalcones for TRAIL-Induced Apoptosis in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Małgorzata Ksek

    2012-11-01

    Full Text Available Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL induces apoptosis in cancer cells without toxicity to normal cells. TRAIL binds to death receptors, TRAIL-R1 (DR4 and TRAIL-R2 (DR5 expressed on cancer cell surface and activates apoptotic pathways. Endogenous TRAIL plays an important role in immune surveillance and defense against cancer cells. However, as more tumor cells are reported to be resistant to TRAIL mediated death, it is important to search for and develop new strategies to overcome this resistance. Chalcones can sensitize cancer cells to TRAIL-induced apoptosis. We examined the cytotoxic and apoptotic effects of TRAIL in combination with four chalcones: chalcone, isobavachalcone, licochalcone A and xanthohumol on HeLa cancer cells. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected using annexin V-FITC staining by flow cytometry and fluorescence microscopy. Death receptor expression was analyzed using flow cytometry. The decreased expression of death receptors in cancer cells may be the cause of TRAIL-resistance. Chalcones enhance TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2. Our study has indicated that chalcones augment the antitumor activity of TRAIL and confirm their cancer chemopreventive properties.

  14. Role of climate variability in the heatstroke death rates of Kanto region in Japan.

    Science.gov (United States)

    Akihiko, Takaya; Morioka, Yushi; Behera, Swadhin K

    2014-07-10

    The death toll by heatstroke in Japan, especially in Kanto region, has sharply increased since 1994 together with large interannual variability. The surface air temperature and humidity observed during boreal summers of 1980-2010 were examined to understand the role of climate in the death toll. The extremely hot days, when the daily maximum temperature exceeds 35 °C, are more strongly associated with the death toll than the conventional Wet Bulb Globe Temperature index. The extremely hot days tend to be associated with El Niño/Southern Oscillation or the Indian Ocean Dipole, suggesting a potential link with tropical climate variability to the heatstroke related deaths. Also, the influence of these climate modes on the death toll has strengthened since 1994 probably related to global warming. It is possible to develop early warning systems based on seasonal climate predictions since recent climate models show excellent predictability skills for those climate modes.

  15. Birth rates among male cancer survivors and mortality rates among their offspring : a population-based study from Sweden

    NARCIS (Netherlands)

    Tang, Siau-Wei; Liu, Jenny; Juay, Lester; Czene, Kamila; Miao, Hui; Salim, Agus; Verkooijen, Helena M; Hartman, Mikael

    2016-01-01

    BACKGROUND: With improvements in treatment of cancer, more men of fertile age are survivors of cancer. This study evaluates trends in birth rates among male cancer survivors and mortality rates of their offspring. METHODS: From the Swedish Multi-generation Register and Cancer Register, we identified

  16. Functionalized magnetic nanowires for chemical and magneto-mechanical induction of cancer cell death

    KAUST Repository

    Martínez-Banderas, Aldo Isaac

    2016-10-24

    Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX. Internalization was assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal analysis, BSA formulations demonstrated higher internalization and less agglomeration. The functionalized NWs generated a comparable cytotoxic effect in breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by free DOX and non-functionalized NWs formulations. A synergistic cytotoxic effect is obtained when a magnetic field (1 mT, 10 Hz) is applied to cells treated with DOX-functionalized BSA or APTES-coated NWs, (~70% at the highest concentration). In summary, a bimodal method for cancer cell destruction was developed by the conjugation of the magneto-mechanical properties of iron NWs with the effect of DOX producing better results than the individual effects.

  17. Functionalized magnetic nanowires for chemical and magneto-mechanical induction of cancer cell death

    Science.gov (United States)

    Martínez-Banderas, Aldo Isaac; Aires, Antonio; Teran, Francisco J.; Perez, Jose Efrain; Cadenas, Jael F.; Alsharif, Nouf; Ravasi, Timothy; Cortajarena, Aitziber L.; Kosel, Jürgen

    2016-01-01

    Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX. Internalization was assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal analysis, BSA formulations demonstrated higher internalization and less agglomeration. The functionalized NWs generated a comparable cytotoxic effect in breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by free DOX and non-functionalized NWs formulations. A synergistic cytotoxic effect is obtained when a magnetic field (1 mT, 10 Hz) is applied to cells treated with DOX-functionalized BSA or APTES-coated NWs, (~70% at the highest concentration). In summary, a bimodal method for cancer cell destruction was developed by the conjugation of the magneto-mechanical properties of iron NWs with the effect of DOX producing better results than the individual effects. PMID:27775082

  18. Functionalized magnetic nanowires for chemical and magneto-mechanical induction of cancer cell death

    Science.gov (United States)

    Martínez-Banderas, Aldo Isaac; Aires, Antonio; Teran, Francisco J.; Perez, Jose Efrain; Cadenas, Jael F.; Alsharif, Nouf; Ravasi, Timothy; Cortajarena, Aitziber L.; Kosel, Jürgen

    2016-10-01

    Exploiting and combining different properties of nanomaterials is considered a potential route for next generation cancer therapies. Magnetic nanowires (NWs) have shown good biocompatibility and a high level of cellular internalization. We induced cancer cell death by combining the chemotherapeutic effect of doxorubicin (DOX)-functionalized iron NWs with the mechanical disturbance under a low frequency alternating magnetic field. (3-aminopropyl)triethoxysilane (APTES) and bovine serum albumin (BSA) were separately used for coating NWs allowing further functionalization with DOX. Internalization was assessed for both formulations by confocal reflection microscopy and inductively coupled plasma-mass spectrometry. From confocal analysis, BSA formulations demonstrated higher internalization and less agglomeration. The functionalized NWs generated a comparable cytotoxic effect in breast cancer cells in a DOX concentration-dependent manner, (~60% at the highest concentration tested) that was significantly different from the effect produced by free DOX and non-functionalized NWs formulations. A synergistic cytotoxic effect is obtained when a magnetic field (1 mT, 10 Hz) is applied to cells treated with DOX-functionalized BSA or APTES-coated NWs, (~70% at the highest concentration). In summary, a bimodal method for cancer cell destruction was developed by the conjugation of the magneto-mechanical properties of iron NWs with the effect of DOX producing better results than the individual effects.

  19. Frankincense derived heavy terpene cocktail boosting breast cancer cell(MDA-MB-231) death in vitro简

    Institute of Scientific and Technical Information of China (English)

    Faruck; Lukmanul; Hakkim; Mohammed; Al-Buloshi; Jamal; Al-Sabahi

    2015-01-01

    Objective: To investigate the anti-cancer effect of frankincense derived heavy oil obtained by Soxhlet extraction method on breast cancer cells(MDA-MB-231), and to study its chemical profile using gas chromatography mass spectrometry analysis.Methods: Hexane was used to extract heavy oil from frankincense resin. Chemical profiling of heavy oil was done using Perkin Elmer Clarus GC system with mass spectrometer. MDA-MB-231 cells were treated with different dilutions(1:1 000, 1:1 500,1:1 750, 1:2 000, 1:2 250, 1:2 500, 1:2 750, 1:3 000, 1:3 250) of heavy oil for 24 h. The cells were observed by using light microscopy. Cell viability was measured by MTT assay.Results: Gas chromatography mass spectrometry chemical profiling of frankincense derived heavy oil revealed the presence of terpenes such as a-pinene(61.56%), a-amyrin(20.6%), b-amyrin(8.1%), b-phellandrene(1.47%) and camphene(1.04%). Heavy terpene cocktail induced significant MDA-MB-231 cell death at each concentration tested. Noticeably, very low concentration of Soxhlet derived heavy terpenes elicits considerable cytotoxicity on MDA-MB-231 cells compared to hydro distillated essential oil derived from frankincense resin.Conclusions: Extracting anti-cancer active principle cocktail by simple Soxhlet method is cost effective and less time consuming. Our in vitro anti-cancer data forms the rationale for us to test heavy terpene complex in breast cancer xenograft model in vivo. Furthermore, fractionation and developing frankincense heavy terpene based breast cancer drug is the major goal of our laboratory.

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

    KAUST Repository

    Contreras, Maria F.

    2015-03-01

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

  1. 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.

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

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    Contreras MF

    2015-03-01

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

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

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    Lee, Y. M.; Heo, T. R.; Lee, K. B.; Jang, K. H.; Kim, H. N.; Lee, S. H.; Jeong, M. H. [Kyungpook National University, Daegu (Korea, Republic of)

    2008-04-15

    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

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

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    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.

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

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    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.

  6. 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.

  7. Parity, Age at First Birth, and Risk of Death from Bladder Cancer: A Population-Based Cohort Study in Taiwan

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    Chiu, Hui-Fen; Chen, Brian K.; Yang, Chun-Yuh

    2016-01-01

    The evidence is limited on the relationship between reproductive factors and bladder cancer (BC). We studied 1,292,462 women who had a first and singleton delivery between 1 January 1978 and 31 December 1987. Each woman in the study cohort was tracked from their first childbirth to 31 December 2009. Vital status of the women was determined by crosswalking records with a computerized mortality database. We used Cox proportional hazard regression models to estimate the hazard ratios (HRs) of death from BC associated with maternal age at first birth and parity. The data showed 63 BC deaths during 34,980,246 person-years of follow-up. BC mortality rate was 0.90 cases for every 100,000 person-years. Compared with women who gave birth under the age of 23, the adjusted HR was 1.24 (95% confidence interval (CI) = 0.66–2.35) for women who gave birth between age 23 and 26 and 2.30 (95% CI = 1.21–4.39) for women who gave birth over the age of 26. Increasing age at first birth (p for trend = 0.01) is associated with a trend in increasing risk of BC mortality. Relative to women who had a single childbirth, the adjusted HRs were 1.17 (95% CI = 0.51–2.69) for women who gave birth to two children, and 1.31 (95% CI = 0.56–3.10) for women with three or more childbirths, respectively. These results were not statistically significant. Study results suggests that giving birth at an early age may confer a protective effect on the risk of death from BC. PMID:27918463

  8. 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.

  9. Pediatric Cancer Genetics Research and an Evolving Preventive Ethics Approach for Return of Results after Death of the Subject.

    Science.gov (United States)

    Scollon, Sarah; Bergstrom, Katie; McCullough, Laurence B; McGuire, Amy L; Gutierrez, Stephanie; Kerstein, Robin; Parsons, D Williams; Plon, Sharon E

    2015-01-01

    The return of genetic research results after death in the pediatric setting comes with unique complexities. Researchers must determine which results and through which processes results are returned. This paper discusses the experience over 15 years in pediatric cancer genetics research of returning research results after the death of a child and proposes a preventive ethics approach to protocol development in order to improve the quality of return of results in pediatric genomic settings.

  10. Clozapine Induces Autophagic Cell Death in Non-Small Cell Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yu-Chun Yin

    2015-02-01

    Full Text Available Background/Aims: Previous studies have shown that patients with schizophrenia have a lower incidence of cancer than the general population, and several antipsychotics have been demonstrated to have cytotoxic effects on cancer cells. However, the mechanisms underlying these results remain unclear. The present study aimed to investigate the effect of clozapine, which is often used to treat patients with refractory schizophrenia, on the growth of non-small cell lung carcinoma cell lines and to examine whether autophagy contributes to its effects. Methods: A549 and H1299 cells were treated with clozapine, and cell cytotoxicity, cell cycle and autophagy were then assessed. The autophagy inhibitor bafilomycin A1 and siRNA-targeted Atg7 were used to determine the role of autophagy in the effect of clozapine. Results: Clozapine inhibited A549 and H1299 proliferation and increased p21 and p27 expression levels, leading to cell cycle arrest. Clozapine also induced a high level of autophagy, but not apoptosis, in both cell lines, and the growth inhibitory effect of clozapine was blunted by treatment with the autophagy inhibitor bafilomycin A1 or with an siRNA targeting atg7. Conclusions: Clozapine inhibits cell proliferation by inducing autophagic cell death in two non-small cell lung carcinoma cell lines. These findings may provide insights into the relationship between clozapine use and the lower incidence of lung cancer among patients with schizophrenia.

  11. 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

  12. Modelling the effect of temperature on specific death rate of the micro-flora of raw cotton wool

    Directory of Open Access Journals (Sweden)

    C.C. Opara

    2013-01-01

    Full Text Available Cotton wool for use in medicine must be sterilized and heat treatment is the most common sterilization technique for bulk processing of agricultural materials. Modelling the effect of temperature variations on specific death rate of the micro-flora of raw cotton wool was carried out in this project. The raw cotton wool was collected from a farmer in Kano State, the most important cotton wool producing state of Nigeria. The micro-flora was determined by inoculating and incubating with 0.85% NaCl diluents and the number of bacteria determined by plate count method. As the sterilization temperatures were varied with increased time, the thermal death rates and thermal death time of the micro-flora were determined for each temperature and these was used in the modelling. The model lnK = 83.9 – 34190(1/T shows that the sterilization temperature has a linear relationship with the death rate constant and it is in line with Arrhenius model.

  13. Cervical screening and cervical cancer death among older women: a population-based, case-control study.

    Science.gov (United States)

    Rustagi, Alison S; Kamineni, Aruna; Weinmann, Sheila; Reed, Susan D; Newcomb, Polly; Weiss, Noel S

    2014-05-01

    Recent research suggests that cervical screening of older women is associated with a considerable decrease in cervical cancer incidence. We sought to quantify the efficacy of cervical cytology screening to reduce death from this disease. Among enrollees of 2 US health plans, we compared Papanicolaou smear screening histories of women aged 55-79 years who died of cervical cancer during 1980-2010 (cases) to those of women at risk of cervical cancer (controls). Controls were matched 2:1 to cases on health plan, age, and enrollment duration. Cytology screening during the detectable preclinical phase, estimated as the 5-7 years before diagnosis during which cervical neoplasia is asymptomatic but cytologically detectable, was ascertained from medical records. A total of 39 cases and 80 controls were eligible. The odds ratio of cervical cancer death associated with screening during the presumed detectable preclinical phase was 0.26 (95% confidence interval: 0.10, 0.63) after adjustment for matching characteristics, smoking, marital status, and race/ethnicity using logistic regression. We estimate that cervical cytology screening of all women aged 55-79 years in the United States could avert 630 deaths annually. These results provide a minimum estimate of the efficacy of human papillomavirus DNA screening-a more sensitive test-to reduce cervical cancer death among older women.

  14. Cancer-secreted AGR2 induces programmed cell death in normal cells

    Science.gov (United States)

    Vitello, Elizabeth A.; Quek, Sue-Ing; Kincaid, Heather; Fuchs, Thomas; Crichton, Daniel J.; Troisch, Pamela; Liu, Alvin Y.

    2016-01-01

    Anterior Gradient 2 (AGR2) is a protein expressed in many solid tumor types including prostate, pancreatic, breast and lung. AGR2 functions as a protein disulfide isomerase in the endoplasmic reticulum. However, AGR2 is secreted by cancer cells that overexpress this molecule. Secretion of AGR2 was also found in salamander limb regeneration. Due to its ubiquity, tumor secretion of AGR2 must serve an important role in cancer, yet its molecular function is largely unknown. This study examined the effect of cancer-secreted AGR2 on normal cells. Prostate stromal cells were cultured, and tissue digestion media containing AGR2 prepared from prostate primary cancer 10-076 CP and adenocarcinoma LuCaP 70CR xenograft were added. The control were tissue digestion media containing no AGR2 prepared from benign prostate 10-076 NP and small cell carcinoma LuCaP 145.1 xenograft. In the presence of tumor-secreted AGR2, the stromal cells were found to undergo programmed cell death (PCD) characterized by formation of cellular blebs, cell shrinkage, and DNA fragmentation as seen when the stromal cells were UV irradiated or treated by a pro-apoptotic drug. PCD could be prevented with the addition of the monoclonal AGR2-neutralizing antibody P3A5. DNA microarray analysis of LuCaP 70CR media-treated vs. LuCaP 145.1 media-treated cells showed downregulation of the gene SAT1 as a major change in cells exposed to AGR2. RT-PCR analysis confirmed the array result. SAT1 encodes spermidine/spermine N1-acetyltransferase, which maintains intracellular polyamine levels. Abnormal polyamine metabolism as a result of altered SAT1 activity has an adverse effect on cells through the induction of PCD. PMID:27283903

  15. Artesunate induces cell death in human cancer cells via enhancing lysosomal function and lysosomal degradation of ferritin.

    Science.gov (United States)

    Yang, Nai-Di; Tan, Shi-Hao; Ng, Shukie; Shi, Yin; Zhou, Jing; Tan, Kevin Shyong Wei; Wong, Wai-Shiu Fred; Shen, Han-Ming

    2014-11-28

    Artesunate (ART) is an anti-malaria drug that has been shown to exhibit anti-tumor activity, and functional lysosomes are reported to be required for ART-induced cancer cell death, whereas the underlying molecular mechanisms remain largely elusive. In this study, we aimed to elucidate the molecular mechanisms underlying ART-induced cell death. We first confirmed that ART induces apoptotic cell death in cancer cells. Interestingly, we found that ART preferably accumulates in the lysosomes and is able to activate lysosomal function via promotion of lysosomal V-ATPase assembly. Furthermore, we found that lysosomes function upstream of mitochondria in reactive oxygen species production. Importantly, we provided evidence showing that lysosomal iron is required for the lysosomal activation and mitochondrial reactive oxygen species production induced by ART. Finally, we showed that ART-induced cell death is mediated by the release of iron in the lysosomes, which results from the lysosomal degradation of ferritin, an iron storage protein. Meanwhile, overexpression of ferritin heavy chain significantly protected cells from ART-induced cell death. In addition, knockdown of nuclear receptor coactivator 4, the adaptor protein for ferritin degradation, was able to block ART-mediated ferritin degradation and rescue the ART-induced cell death. In summary, our study demonstrates that ART treatment activates lysosomal function and then promotes ferritin degradation, subsequently leading to the increase of lysosomal iron that is utilized by ART for its cytotoxic effect on cancer cells. Thus, our data reveal a new mechanistic action underlying ART-induced cell death in cancer cells.

  16. 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.

  17. Myeloid zinc finger 1 mediates sulindac sulfide-induced upregulation of death receptor 5 of human colon cancer cells

    OpenAIRE

    Mano Horinaka; Tatsushi Yoshida; Mitsuhiro Tomosugi; Shusuke Yasuda; Yoshihiro Sowa; Toshiyuki Sakai

    2014-01-01

    A combined therapy of sulindac sulfide and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising strategy for the treatment of cancer. Sulindac sulfide had been shown to induce the expression of death receptor 5 (DR5), a receptor for TRAIL, and sensitize cancer cells to TRAIL-induced apoptosis; however, the molecular mechanism underlying the upregulation of DR5 has not yet been elucidated. We demonstrate here that myeloid zinc finger 1 (MZF1) mediates the induction of...

  18. Does desire for hastened death change in terminally ill cancer patients?

    Science.gov (United States)

    Rosenfeld, Barry; Pessin, Hayley; Marziliano, Allison; Jacobson, Colleen; Sorger, Brooke; Abbey, Jennifer; Olden, Megan; Brescia, Robert; Breitbart, William

    2014-06-01

    Understanding why some terminally ill patients may seek a hastened death (a construct referred to as "desire for hastened death" or DHD) is critical to understanding how to optimize quality of life during an individual's final weeks, months or even years of life. Although a number of predictor variables have emerged in past DHD research, there is a dearth of longitudinal research on how DHD changes over time and what factors might explain such changes. This study examined DHD over time in a sample of terminally ill cancer patients admitted to a palliative care hospital. A random sample of 128 patients completed the Schedule of Attitudes toward Hastened Death (SAHD) at two time points approximately 2-4 weeks apart participated. Patients were categorized into one of four trajectories based on their SAHD scores at both time points: low (low DHD at T1 and T2), rising (low DHD at T1 and high DHD at T2), falling (high DHD at T1 and low DHD at T2) and high (high DHD at T1 and T2). Among patients who were low at T1, several variables distinguished between those who developed DHD and those who did not: physical symptom distress, depression symptom severity, hopelessness, spiritual well-being, baseline DHD, and a history of mental health treatment. However, these same medical and clinical variables did not distinguish between the falling and high trajectories. Overall, there appears to be a relatively high frequency of change in DHD, even in the last weeks of life. Interventions designed to target patients who are exhibiting subthreshold DHD and feelings of hopelessness may reduce the occurrence of DHD emerging in this population.

  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. 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.

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

    Science.gov (United States)

    Kanugula, Anantha Koteswararao; Dhople, Vishnu M; Völker, Uwe; Ummanni, Ramesh; Kotamraju, Srigiridhar

    2014-01-01

    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.

  2. Improving cervical cancer screening rates in an urban HIV clinic.

    Science.gov (United States)

    Cross, Sara L; Suharwardy, Sanaa H; Bodavula, Phani; Schechtman, Kenneth; Overton, E Turner; Onen, Nur F; Lane, Michael A

    2014-01-01

    Human immunodeficiency virus (HIV)-infected women are at increased risk of invasive cervical cancer; however, screening rates remain low. The objectives of this study were to analyze a quality improvement intervention to increase cervical cancer screening rates in an urban academic HIV clinic and to identify factors associated with inadequate screening. Barriers to screening were identified by a multidisciplinary quality improvement committee at the Washington University Infectious Diseases clinic. Several strategies were developed to address these barriers. The years pre- and post-implementation were analyzed to examine the clinical impact of the intervention. A total of 422 women were seen in both the pre-implementation and post-implementation periods. In the pre-implementation period, 222 women (53%) underwent cervical cancer screening in the form of Papanicolaou (Pap) testing. In the post-implementation period, 318 women (75.3%) underwent cervical cancer screening (p screening included fewer visits attended (pre: 4.2 ± 1.5; post: 3.4 ± 1.4; p screening rates in an urban academic HIV clinic.

  3. Prostate Cancer Cell Telomere Length Variability and Stromal Cell Telomere Length as Prognostic Markers for Metastasis and Death

    Science.gov (United States)

    Heaphy, Christopher M.; Yoon, Ghil Suk; Peskoe, Sarah B.; Joshu, Corinne E.; Lee, Thomas K.; Giovannucci, Edward; Mucci, Lorelei A.; Kenfield, Stacey A.; Stampfer, Meir J.; Hicks, Jessica L.; De Marzo, Angelo M.; Platz, Elizabeth A.; Meeker, Alan K.

    2013-01-01

    Current prognostic indicators are imperfect predictors of outcome in men with clinicallylocalized prostate cancer. Thus, tissue-based markers are urgently needed to improve treatment and surveillance decision-making. Given that shortened telomeres enhance chromosomal instability and such instability is a hallmark of metastatic lesions, we hypothesized that alterations in telomere length in the primary cancer would predict risk of progression to metastasis and prostate cancer death. To test this hypothesis, we conducted a prospective cohort study of 596 surgically treated men who participated in the ongoing Health Professionals Follow-up Study. Men who had the combination of more variable telomere length among prostate cancer cells (cell-to-cell) and shorter telomere length in prostate cancer-associated stromal cells were substantially more likely to progress to metastasis or die of their prostate cancer. These findings point to the translational potential of this telomere biomarker for prognostication and risk stratification for individualized therapeutic and surveillance strategies. PMID:23779129

  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. 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 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.

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

    Science.gov (United States)

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

    2011-09-01

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

  7. 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…

  8. Benzyl isothiocyanate causes FoxO1-mediated autophagic death in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Dong Xiao

    Full Text Available Benzyl isothiocyanate (BITC, a constituent of edible cruciferous vegetables, inhibits growth of breast cancer cells but the mechanisms underlying growth inhibitory effect of BITC are not fully understood. Here, we demonstrate that BITC treatment causes FoxO1-mediated autophagic death in cultured human breast cancer cells. The BITC-treated breast cancer cells (MDA-MB-231, MCF-7, MDA-MB-468, BT-474, and BRI-JM04 and MDA-MB-231 xenografts from BITC-treated mice exhibited several features characteristic of autophagy, including appearance of double-membrane vacuoles (transmission electron microscopy and acidic vesicular organelles (acridine orange staining, cleavage of microtubule-associated protein 1 light chain 3 (LC3, and/or suppression of p62 (p62/SQSTM1 or sequestosome 1 expression. On the other hand, a normal human mammary epithelial cell line (MCF-10A was resistant to BITC-induced autophagy. BITC-mediated inhibition of MDA-MB-231 and MCF-7 cell viability was partially but statistically significantly attenuated in the presence of autophagy inhibitors 3-methyl adenine and bafilomycin A1. Stable overexpression of Mn-superoxide dismutase, which was fully protective against apoptosis, conferred only partial protection against BITC-induced autophagy. BITC treatment decreased phosphorylation of mTOR and its downstream targets (P70s6k and 4E-BP1 in cultured MDA-MB-231 and MCF-7 cells and MDA-MB-231 xenografts, but activation of mTOR by transient overexpression of its positive regulator Rheb failed to confer protection against BITC-induced autophagy. Autophagy induction by BITC was associated with increased expression and acetylation of FoxO1. Furthermore, autophagy induction and cell growth inhibition resulting from BITC exposure were significantly attenuated by small interfering RNA knockdown of FoxO1. In conclusion, the present study provides novel insights into the molecular circuitry of BITC-induced cell death involving FoxO1-mediated autophagy.

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

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    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

  10. 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.

  11. HDAC1 inactivation induces mitotic defect and caspase-independent autophagic cell death in liver cancer.

    Directory of Open Access Journals (Sweden)

    Hong Jian Xie

    Full Text Available Histone deacetylases (HDACs are known to play a central role in the regulation of several cellular properties interlinked with the development and progression of cancer. Recently, HDAC1 has been reported to be overexpressed in hepatocellular carcinoma (HCC, but its biological roles in hepatocarcinogenesis remain to be elucidated. In this study, we demonstrated overexpression of HDAC1 in a subset of human HCCs and liver cancer cell lines. HDAC1 inactivation resulted in regression of tumor cell growth and activation of caspase-independent autophagic cell death, via LC3B-II activation pathway in Hep3B cells. In cell cycle regulation, HDAC1 inactivation selectively induced both p21(WAF1/Cip1 and p27(Kip1 expressions, and simultaneously suppressed the expression of cyclin D1 and CDK2. Consequently, HDAC1 inactivation led to the hypophosphorylation of pRb in G1/S transition, and thereby inactivated E2F/DP1 transcription activity. In addition, we demonstrated that HDAC1 suppresses p21(WAF1/Cip1 transcriptional activity through Sp1-binding sites in the p21(WAF1/Cip1 promoter. Furthermore, sustained suppression of HDAC1 attenuated in vitro colony formation and in vivo tumor growth in a mouse xenograft model. Taken together, we suggest the aberrant regulation of HDAC1 in HCC and its epigenetic regulation of gene transcription of autophagy and cell cycle components. Overexpression of HDAC1 may play a pivotal role through the systemic regulation of mitotic effectors in the development of HCC, providing a particularly relevant potential target in cancer therapy.

  12. Temporal Trends in Geographical Variation in Breast Cancer Mortality in China, 1973–2005: An Analysis of Nationwide Surveys on Cause of Death

    Directory of Open Access Journals (Sweden)

    Changfa Xia

    2016-09-01

    Full Text Available To describe geographical variation in breast cancer mortality over time, we analysed breast cancer mortality data from three retrospective national surveys on causes of death in recent decades in China. We first calculated the age-standardized mortality rate (ASMR for each of the 31 provinces in mainland China stratified by survey period (1973–1975, 1990–1992 and 2004–2005. To test whether the geographical variation in breast cancer mortality changed over time, we then estimated the rate ratio (RR for the aggregated data for seven regions and three economic zones using generalized linear models. Finally, we examined the correlation between mortality rate and several macro-economic measures at the provincial level. We found that the overall ASMR increased from 2.98 per 100,000 in 1973–1975 to 3.08 per 100,000 in 1990–1992, and to 3.85 per 100,000 in 2004–2005. Geographical variation in breast cancer mortality also increased significantly over time at the regional level (p = 0.002 but not at the economic zone (p = 0.089 level, with RR being generally lower for Western China (Northwest and Southwest and higher in Northeast China over the three survey periods. These temporal and spatial trends in breast cancer mortality were found to be correlated with per capita gross domestic product, number of hospitals and health centres’ beds per 10,000 population and number of practicing doctors per 10,000 population, and average number of live births for women aged 15–64. It may be necessary to target public health policies in China to address the widening geographic variation in breast cancer mortality, and to take steps to ensure that the ease of access and the quality of cancer care across the country is improved for all residents.

  13. Temporal Trends in Geographical Variation in Breast Cancer Mortality in China, 1973–2005: An Analysis of Nationwide Surveys on Cause of Death

    Science.gov (United States)

    Xia, Changfa; Kahn, Clare; Wang, Jinfeng; Liao, Yilan; Chen, Wanqing; Yu, Xue Qin

    2016-01-01

    To describe geographical variation in breast cancer mortality over time, we analysed breast cancer mortality data from three retrospective national surveys on causes of death in recent decades in China. We first calculated the age-standardized mortality rate (ASMR) for each of the 31 provinces in mainland China stratified by survey period (1973–1975, 1990–1992 and 2004–2005). To test whether the geographical variation in breast cancer mortality changed over time, we then estimated the rate ratio (RR) for the aggregated data for seven regions and three economic zones using generalized linear models. Finally, we examined the correlation between mortality rate and several macro-economic measures at the provincial level. We found that the overall ASMR increased from 2.98 per 100,000 in 1973–1975 to 3.08 per 100,000 in 1990–1992, and to 3.85 per 100,000 in 2004–2005. Geographical variation in breast cancer mortality also increased significantly over time at the regional level (p = 0.002) but not at the economic zone (p = 0.089) level, with RR being generally lower for Western China (Northwest and Southwest) and higher in Northeast China over the three survey periods. These temporal and spatial trends in breast cancer mortality were found to be correlated with per capita gross domestic product, number of hospitals and health centres’ beds per 10,000 population and number of practicing doctors per 10,000 population, and average number of live births for women aged 15–64. It may be necessary to target public health policies in China to address the widening geographic variation in breast cancer mortality, and to take steps to ensure that the ease of access and the quality of cancer care across the country is improved for all residents. PMID:27690073

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

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    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.

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

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    Minyong Kang

    2014-05-01

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

  16. Invariant death

    Science.gov (United States)

    Frank, Steven A.

    2016-01-01

    In nematodes, environmental or physiological perturbations alter death’s scaling of time. In human cancer, genetic perturbations alter death’s curvature of time. Those changes in scale and curvature follow the constraining contours of death’s invariant geometry. I show that the constraints arise from a fundamental extension to the theories of randomness, invariance and scale. A generalized Gompertz law follows. The constraints imposed by the invariant Gompertz geometry explain the tendency of perturbations to stretch or bend death’s scaling of time. Variability in death rate arises from a combination of constraining universal laws and particular biological processes.

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

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    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.

  18. Role of immunohistochemical overexpression of matrix metalloproteinases MMP-2 and MMP-11 in the prognosis of death by ovarian cancer.

    Science.gov (United States)

    Périgny, Martine; Bairati, Isabelle; Harvey, Isabelle; Beauchemin, Michel; Harel, François; Plante, Marie; Têtu, Bernard

    2008-02-01

    Matrix metalloproteinases (MMPs) are enzymes thought to be involved in tumor invasion. We hypothesized that MMP-2 and MMP-11 overexpression was associated with the aggressiveness of ovarian carcinoma. This study was performed on samples from 100 patients with stage III ovarian carcinomas treated surgically between 1990 and 2000. Immunohistochemical staining was performed on ovarian tumors and peritoneal implants using monoclonal antibodies. Overexpression was defined as more than 10% of cells expressing the marker. Multivariate analyses showed that only MMP-2 overexpression by cancer cells in peritoneal implants was associated with a significant risk of death by disease (hazard ratio, 2.65; 95% confidence interval, 1.41-4.97; P =.003). MMP-11 overexpression was not predictive of survival. These results suggest that MMP-2 overexpression by cancer cells in peritoneal implants and not in the primary ovarian cancer is predictive of ovarian cancer prognosis and more likely reflects the presence of particularly aggressive clones of cancer cells.

  19. Global cancer statistics, 2012.

    Science.gov (United States)

    Torre, Lindsey A; Bray, Freddie; Siegel, Rebecca L; Ferlay, Jacques; Lortet-Tieulent, Joannie; Jemal, Ahmedin

    2015-03-01

    Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly

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

    Science.gov (United States)

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

    2011-04-01

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

  1. Selection of Aptamers for CED-9/Bcl-2 Family Cell Death Regulations and Their Application in Study of Apoptosis Regulation and Drug Design for Breast Cancer

    Science.gov (United States)

    2005-07-01

    Apoptosis Regulation and Drug Design for Breast Cancer PRINCIPAL INVESTIGATOR: Ding Xue, Ph.D. Chonglin Yang, Ph.D. Nathan Camp CONTRACTING ORGANIZATION...Aptamers for CED-9/Bcl-2 Family Cell Death Regulations and Their Application in Study of Apoptosis Regulation and Drug Design for Breast Cancer 5b. GRANT...aptamers for CED-9/Bcl-2 family cell death regulators and their application in study of apoptosis regulation and drug design for breast cancer. The 4th Era

  2. Contribution of mitochondria and lysosomes to photodynamic therapy-induced death in cancer cells

    Science.gov (United States)

    Nieminen, Anna-Liisa; Azizuddin, Kashif; Zhang, Ping; Kenney, Malcolm E.; Pediaditakis, Peter; Lemasters, John J.; Oleinick, Nancy L.

    2008-02-01

    In photodynamic therapy (PDT), visible light activates a photosensitizing drug added to a tissue, resulting in singlet oxygen formation and cell death. Employing confocal microscopy, we previously found that the phthalocyanine Pc 4 localized primarily to mitochondrial membranes in various cancer cell lines, resulting in mitochondrial reactive oxygen species (ROS) production, followed by inner membrane permeabilization (mitochondrial permeability transition) with mitochondrial depolarization and swelling, which in turn led to cytochrome c release and apoptotic death. Recently, derivatives of Pc 4 with OH groups added to one of the axial ligands were synthesized. These derivatives appeared to be taken up more avidly by cells and caused more cytotoxicity than the parent compound Pc 4. Using organelle-specific fluorophores, we found that one of these derivatives, Pc 181, accumulated into lysosomes and that PDT with Pc 181 caused rapid disintegration of lysosomes. We hypothesized that chelatable iron released from lysosomes during PDT contributes to mitochondrial damage and subsequent cell death. We monitored cytosolic Fe2+ concentrations after PDT with calcein. Fe2+ binds to calcein causing quenching of calcein fluorescence. After bafilomycin, an inhibitor of the vacuolar proton-translocating ATPase, calcein fluorescence became quenched, an effect prevented by starch desferal s-DFO, an iron chelator that enters cells by endocytosis. After Pc 181-PDT, cytosolic calcein fluorescence also decreased, indicating increased chelatable Fe2+ in the cytosol, and apoptosis occurred. s-DFO decreased Pc 181-PDT-induced apoptosis as measured by a decrease of caspase-3 activation. In isolated mitochondria preparations, Fe2+ induced mitochondrial swelling, which was prevented by Ru360, an inhibitor of the mitochondrial Ca2+ uniporter. The data support a hypothesis of oxidative injury in which Pc 181-PDT disintegrates lysosomes and releases constituents that synergistically promote

  3. Categorizing extent of tumor cell death response to cancer therapy using quantitative ultrasound spectroscopy and maximum mean discrepancy.

    Science.gov (United States)

    Gangeh, Mehrdad J; Sadeghi-Naini, Ali; Diu, Michael; Tadayyon, Hadi; Kamel, Mohamed S; Czarnota, Gregory J

    2014-06-01

    Quantitative ultrasound (QUS) spectroscopic techniques in conjunction with maximum mean discrepancy (MMD) have been proposed to detect, and to classify noninvasively the levels of cell death in response to cancer therapy administration in tumor models. Evaluation of xenograft tumor responses to cancer treatments were carried out using conventional-frequency ultrasound at different times after chemotherapy exposure. Ultrasound data were analyzed using spectroscopic techniques and multi-parametric QUS spectral maps were generated. MMD was applied as a distance criterion, measuring alterations in each tumor in response to chemotherapy, and the extent of cell death was classified into less/more than 20% and 40% categories. Statistically significant differences were observed between "pre-" and "post-treatment" groups at different times after chemotherapy exposure, suggesting a high capability of proposed framework for detecting tumor response noninvasively. Promising results were also obtained for categorizing the extent of cell death response in each tumor using the proposed framework, with gold standard histological quantification of cell death as ground truth. The best classification results were obtained using MMD when applied on histograms of QUS parametric maps. In this case, classification accuracies of 84.7% and 88.2% were achieved for categorizing extent of tumor cell death into less/more than 20% and 40%, respectively.

  4. 徐州市城区居民肺癌死亡情况及潜在寿命损失分析%Analysis of lung cancer death situation and potential life loss of residents in Xuzhou urban areas

    Institute of Scientific and Technical Information of China (English)

    赵广法; 余加席; 安晓红

    2006-01-01

    BACKGROUND: Lung cancer keeps the first place in malignant tumor death all along. It is quite necessary to clarify the situation and tendency change of residents' lung cancer death for formulating prevention and cure strategy.OBJECTIVE: To investigate the lung cancer death characteristics, death trend and result out potential life loss of the residents in urban areas of Xuzhou.DESIGN: A retrospective descriptive epidemiology study.SETTING: Center for Disease Prevention and Control of Xuzhou.PARTICIPANTS: Totally 3 890 cases died of lung cancer between 1990 and 2003 in the urban areas of Xuzhou city. METHODS: Residents' lung cancer death characteristics and potential life span loss situation with parameters of crude death rate, standardized death rate, age specific death rate and potential life span loss and other indexes of the residents in the urban areas of Xuzhou city in 1990 and 2003were described.MAIN OUTCOME MEASURES: ①Crude death rate of lung cancer;②Potential life span loss; ③Life lost rate.RESULTS: ①During 14 years period , 3 890 cases of lung cancer death happened ,which accounted for 27.43% of total cases of malignant tumor death; ② year average death rate was 28.31/100 thousand, standardized death rate was 24.88/100 thousand, residents' potential life span loss caused by lung cancer death accounted for 24 230 people per year③ life decreasing rate was 1.19/1 000, standardized life decreasing rate was 1.45/1 000, each case of lung cancer death resulted in potential life loss of 6.23 years; males' death rate was higher than females'(x2=575.70,P < 0.01), the ratio of male to female was 2.31:1. Age specific death rate of male and female after 20 years of age increased in an exponential manner.CONCLUSION: Lung cancer is the most serious malignant tumor that threatens the life health of residents in urban areas of Xuzhou city; the potential life span loss caused by lung cancer is very big. The amount of carcinogenic substances exposed in

  5. 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.

  6. Androstane derivatives induce apoptotic death in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Jakimov, Dimitar S; Kojić, Vesna V; Aleksić, Lidija D; Bogdanović, Gordana M; Ajduković, Jovana J; Djurendić, Evgenija A; Penov Gaši, Katarina M; Sakač, Marija N; Jovanović-Šanta, Suzana S

    2015-11-15

    Biological investigation was conducted to study in vitro antiproliferative and pro-apoptotic potential of selected 17α-picolyl and 17(E)-picolinylidene androstane derivatives. The antiproliferative impact was examined on six human tumor cell lines, including two types of breast (MCF-7 and MDA-MB-231), prostate (PC3), cervical (HeLa), colon (HT 29) and lung cancer (A549), as well as one normal fetal lung fibroblasts cell line (MRC-5). All derivatives selectively decreased proliferation of estrogen receptor negative MDA-MB-231 breast cancer cells after 48 h and 72 h treatment and compounds showed time-dependent activity. We used this cell line to investigate cell cycle modulation and apoptotic cell death induction by flow cytometry, expression of apoptotic proteins by Western blot and apoptotic morphology by visual observation. Tested androstane derivatives affected the cell cycle distribution and induced apoptosis and necrosis. Compounds had different and specific mode of action, depending on derivative type and exposure time. Some compounds induced significant apoptosis measured by Annexin V test compared to reference compound formestane. Higher expression of pro-apoptotic BAX, downregulation of anti-apoptotic Bcl-2 and cleavage of PARP protein were confirmed in almost all treated samples, but the lack of caspase-3 activation suggested the induction of apoptosis in caspase-independent manner. More cells with apoptotic morphology were observed in samples after prolonged treatment. Structure-activity relationship analysis was performed to find correlations between the structure variations of investigated derivatives and observed biological effects. Results of this study showed that some of the investigated androstane derivatives have good biomedical potential and could be candidates for anticancer drug development.

  7. Colorectal cancer incidence rates have decreased in central Italy.

    Science.gov (United States)

    Crocetti, Emanuele; Buzzoni, Carlotta; Zappa, Marco

    2010-11-01

    We analyzed colorectal cancer incidence data from the Tuscany Cancer Registry, central Italy, for the period 1985-2005. We carried out a trend analysis through a Joinpoint regression analysis, and summarized trends as annual percent change (APC) of the standardized (European standard) rates. Colorectal incidence rates increased until 1996 (APC=+1.4, 95% CI: 0.8-1.9), then decreased significantly (APC=-1.1, 95% CI: -0.8 to -0.4). The change was detected as statistically significant in the age group of 54+ years. Among younger individuals, we observed an increasing incidence until 2003. In the same geographical area, a colorectal screening programme has been active from 1982; it was initially based on guaiac faecal occult blood testing (GFOBT) and on immunological testing (IFOBT) since the mid 1990s. The decline in colorectal cancer incidence since 1996, in the whole population and especially among individuals older than 54 years, may suggest the effect of FOBT screening in terms of precancerous polyps removal.

  8. 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

  9. Ruta 6 selectively induces cell death in brain cancer cells but proliferation in normal peripheral blood lymphocytes: A novel treatment for human brain cancer.

    Science.gov (United States)

    Pathak, Sen; Multani, Asha S; Banerji, Pratip; Banerji, Prasanta

    2003-10-01

    Although conventional chemotherapies are used to treat patients with malignancies, damage to normal cells is problematic. Blood-forming bone marrow cells are the most adversely affected. It is therefore necessary to find alternative agents that can kill cancer cells but have minimal effects on normal cells. We investigated the brain cancer cell-killing activity of a homeopathic medicine, Ruta, isolated from a plant, Ruta graveolens. We treated human brain cancer and HL-60 leukemia cells, normal B-lymphoid cells, and murine melanoma cells in vitro with different concentrations of Ruta in combination with Ca3(PO4)2. Fifteen patients diagnosed with intracranial tumors were treated with Ruta 6 and Ca3(PO4)2. Of these 15 patients, 6 of the 7 glioma patients showed complete regression of tumors. Normal human blood lymphocytes, B-lymphoid cells, and brain cancer cells treated with Ruta in vitro were examined for telomere dynamics, mitotic catastrophe, and apoptosis to understand the possible mechanism of cell-killing, using conventional and molecular cytogenetic techniques. Both in vivo and in vitro results showed induction of survival-signaling pathways in normal lymphocytes and induction of death-signaling pathways in brain cancer cells. Cancer cell death was initiated by telomere erosion and completed through mitotic catastrophe events. We propose that Ruta in combination with Ca3(PO4)2 could be used for effective treatment of brain cancers, particularly glioma.

  10. 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.

  11. Indole diketopiperazines from endophytic Chaetomium sp 88194 induce breast cancer cell apoptotic death.

    Science.gov (United States)

    Wang, Fu-qian; Tong, Qing-yi; Ma, Hao-ran; Xu, Hong-feng; Hu, Song; Ma, Wei; Xue, Yong-bo; Liu, Jun-jun; Wang, Jian-ping; Song, Hong-ping; Zhang, Jin-wen; Zhang, Geng; Zhang, Yong-hui

    2015-03-19

    Diketopiperazines are important secondary metabolites of the fungi with variety bioactivities. Several species belonging to genus Chaetomium produce compounds of this class, such as chetomin. To identify new antitumor agents, secondary metabolites of fungus Chaetomium sp 88194 were investigated and three new indole diketopiperazines, Chaetocochins G (1), Oidioperazines E (2) and Chetoseminudin E (3), along with two known compounds Chetoseminudins C (4) and N-acetyl-β-oxotryptamine (5), were obtained. Chaetocochins G and Chetoseminudin E were recrystallized in CHCl3 containing a small amount of MeOH, and their structures with absolute configuration were established by spectroscopic data interpretation and single-crystal X-ray diffraction analysis. The absolute configuration of Oidioperazines E was defined by comparing of experimental and calculated electronic circular dichroism spectra. These isolates were also evaluated the anticancer activity, and Chaetocochins G displayed more potent cytotoxicity in MCF-7 cells than the common chemotherapeutic agent (5-fluorouracil) associated with G2/M cell cycle arrest. More importantly, Chaetocochins G induced cell apoptotic death via caspase-3 induction and proteolytic cleavage of poly (ADP-ribose) polymerase, concomitantly with increased Bax and decreased Bcl-2 expression. Our findings suggested that indole diketopiperazines from endophytic Chaetomium sp 88194 may be potential resource for developing anti-cancer reagents.

  12. Impact of delayed diagnosis time in estimating progression rates to hepatitis C virus-related cirrhosis and death.

    Science.gov (United States)

    Fu, Bo; Wang, Wenbin; Shi, Xin

    2015-12-01

    Delay of the diagnosis of hepatitis C virus (HCV), and its treatment to avert cirrhosis, is often present sincethe early stage of HCV progression is latent. Current methods to determine the incubation time to HCV-related cirrhosis and the duration time from cirrhosis to subsequent events (e.g. complications or death) used to be based on the time of liver biopsy diagnosis and ignore this delay which led to an interval censoring for the first event time and a double censoring for the subsequent event time. To investigate the impact of this delay in estimating HCV progression rates and relevant estimating bias, we present a correlated two-stage progression model for delayed diagnosis time and fit the developed model to the previously studied hepatitis C cohort data from Edinburgh. Our analysis shows that taking the delayed diagnosis into account gives a mildly different estimate of progression rate to cirrhosis and significantly lower estimated progression rate to HCV-related death in comparison with conventional modelling. We also find that when the delay increases, the bias in estimating progression increases significantly.

  13. Reliability of the interval death rate analysis for estimating the time course of the motoneurone afterhyperpolarization in humans.

    Science.gov (United States)

    MacDonell, Christopher William; Ivanova, Tanya Dimitrova; Garland, S Jayne

    2007-05-15

    The reliability of the afterhyperpolarization (AHP) time course, as estimated by the interval death rate (IDR) analysis was evaluated both within and between investigators. The IDR analysis uses the firing history of a single motor unit train at low tonic firing rates to calculate an estimate of the AHP time course [Matthews PB. Relationship of firing intervals of human motor units to the trajectory of post-spike after-hyperpolarization and synaptic noise. J Physiol 1996;492:597-628]. Single motor unit trains were collected from the tibialis anterior (TA) to determine intra-rater reliability (within investigator). Data from the first dorsal interosseus (FDI), collected in a previous investigation [Gossen ER, Ivanova TD, Garland SJ. The time course of the motoneurone afterhyperpolarization is related to motor unit twitch speed in human skeletal muscle. J Physiol 2003;552:657-64], were used to examine the inter-rater reliability (between investigators). The lead author was blinded to the original time constants and file identities for the re-analysis. The intra-rater reliability of the AHP time constant in the TA data was high (r(2)=0.88; pFDI data was also strong (r(2)=0.92; pFDI. It is concluded that the interval death rate analysis is a reliable tool for estimating the AHP time course with experienced investigators.

  14. Natural product Celastrol destabilizes tubulin heterodimer and facilitates mitotic cell death triggered by microtubule-targeting anti-cancer drugs.

    Directory of Open Access Journals (Sweden)

    Hakryul Jo

    Full Text Available BACKGROUND: Microtubule drugs are effective anti-cancer agents, primarily due to their ability to induce mitotic arrest and subsequent cell death. However, some cancer cells are intrinsically resistant or acquire a resistance. Lack of apoptosis following mitotic arrest is thought to contribute to drug resistance that limits the efficacy of the microtubule-targeting anti-cancer drugs. Genetic or pharmacological agents that selectively facilitate the apoptosis of mitotic arrested cells present opportunities to strengthen the therapeutic efficacy. METHODOLOGY AND PRINCIPAL FINDINGS: We report a natural product Celastrol targets tubulin and facilitates mitotic cell death caused by microtubule drugs. First, in a small molecule screening effort, we identify Celastrol as an inhibitor of neutrophil chemotaxis. Subsequent time-lapse imaging analyses reveal that inhibition of microtubule-mediated cellular processes, including cell migration and mitotic chromosome alignment, is the earliest events affected by Celastrol. Disorganization, not depolymerization, of mitotic spindles appears responsible for mitotic defects. Celastrol directly affects the biochemical properties of tubulin heterodimer in vitro and reduces its protein level in vivo. At the cellular level, Celastrol induces a synergistic apoptosis when combined with conventional microtubule-targeting drugs and manifests an efficacy toward Taxol-resistant cancer cells. Finally, by time-lapse imaging and tracking of microtubule drug-treated cells, we show that Celastrol preferentially induces apoptosis of mitotic arrested cells in a caspase-dependent manner. This selective effect is not due to inhibition of general cell survival pathways or mitotic kinases that have been shown to enhance microtubule drug-induced cell death. CONCLUSIONS AND SIGNIFICANCE: We provide evidence for new cellular pathways that, when perturbed, selectively induce the apoptosis of mitotic arrested cancer cells, identifying a

  15. Noninvasive indocyanine green plasma disappearance rate predicts early complications, graft failure or death after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Lutz Schneider; Martin Spiegel; Sebastian Latanowicz; Markus A Weigand; Jan Schmidt; Jens Werner; Wolfgang Stremmel; Christoph Eisenbach

    2011-01-01

    BACKGROUND: Early  detection  of  graft  malfunction  or postoperative  complications  is  essential  to  save  patients  and organs after orthotopic liver transplantation (OLT). Predictive tests  for  graft  dysfunction  are  needed  to  enable  earlier implementation  of  organ-saving  interventions  following transplantation. This study was undertaken to assess the value of indocyanine green plasma disappearance rates (ICG-PDRs) for predicting postoperative complications, graft dysfunction, and patient survival following OLT. METHODS: Eighty-six patients undergoing OLT were included in this single-centre trial. ICG-PDR was assessed daily for the first 7 days following OLT. Endpoints were graft loss or death within 30 days and postoperative complications, graft loss, or death within 30 days. RESULTS: Postoperative complications of 31 patients included deaths (12 patients) or graft losses. ICG-PDR was significantly different in patients whose endpoints were graft loss or death beginning from day 3 and in those whose endpoints were graft-loss,  death,  or  postoperative  complications  beginning  from day  4  after  OLT.  For  day  7  measurements,  receiver  operating characteristic  curve  analysis  revealed  an  ICG-PDR  cut-off  for predicting  death  or  graft  loss  of  9.6%  per  min  (a  sensitivity of 75.0%, a specificity of 72.6%, positive predictive value 0.35, negative predictive value 0.94). For prediction of graft loss, death, or postoperative complications, the ICG-PDR cut-off was 12.3% per min (a sensitivity of 68.9%,

  16. 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

    2016-04-11

    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.

  17. Effects of Environmental Factors on Death Rate of Pigs in South Korea

    OpenAIRE

    Lee, Seung-Joo; Oh, Taek-Kuen; Kim, Suk; Min, Won-Gi; Gutierrez, Winson-Montanez; Chang, Hong-Hee; Chikushi, Jiro

    2012-01-01

    Reducing the mortality rate among pigs for a swine industry is very important. In this study, environmental factors such as average air temperature, average daily temperature rage and average relative humidity were determined on its effects of on mortality rate of pigs and its optimum ranges to influence pigs health that were correlated with the pigs periodic growth. Data were collected from 10 pig farms in South Korea during the Summer, Fall and Winter seasons. Correlation and regression equ...

  18. Low heart rate variability and cancer-related fatigue in breast cancer survivors.

    Science.gov (United States)

    Crosswell, Alexandra D; Lockwood, Kimberly G; Ganz, Patricia A; Bower, Julienne E

    2014-07-01

    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 association between lower parasympathetic activity and higher fatigue in breast cancer survivors (Fagundes et al., 2011), and to examine whether inflammation mediates this association. Study participants were drawn from two samples and included 84 women originally diagnosed with early stage breast cancer prior to age 50. Participants completed questionnaires, provided blood samples for determination of interleukin (IL)-6 and C-reactive protein (CRP), and underwent electrocardiography (ECG) assessment for evaluation of resting heart rate variability (HRV), a measure of parasympathetic activity. Results showed that lower HRV was associated with higher fatigue (pcancer-related fatigue, but suggest that inflammation does not mediate this association in younger, healthy breast cancer survivors who are several years post-treatment. The autonomic nervous system merits additional attention in research on the etiology of cancer-related fatigue.

  19. High CD10 expression in lymph node metastases from surgically treated prostate cancer independently predicts early death.

    Science.gov (United States)

    Fleischmann, Achim; Rocha, Carla; Saxer-Sekulic, Nikolina; Zlobec, Inti; Sauter, Guido; Thalmann, George N

    2011-06-01

    Patients with nodal positive prostate cancers are an important cohort with poorly defined risk factors. CD10 is a cell surface metallopeptidase that has been suggested to play a role in prostate cancer progression. CD10 expression was evaluated in 119 nodal positive prostate cancer patients using tissue microarrays constructed from primary tumors and lymph node metastases. All patients underwent radical prostatectomy and standardized extended lymphadenectomy. They had no neoadjuvant therapy and received deferred androgen deprivation. In the primary tumor, high CD10 expression was significantly associated with earlier death from disease when compared with low CD10 expression (5-year survival 73.7% vs. 91.8%; p = 0.043). In the metastases, a high CD10 expression was significantly associated with larger total size of metastases (median 11.4 vs. 6.5 mm; p = 0.015), earlier death of disease (5-year survival 71.5% vs. 87.3%; p = 0.017), and death of any cause (5-year survival 70.0% vs. 87.2%; p = 0.001) when compared with low CD10 expression. CD10 expression in the metastases added independent prognostic information for overall survival (p = 0.029) after adjustment for Gleason score of the primary tumor, nodal tumor burden, and resection margins. In conclusion, a high CD10 expression in prostate cancer predicts early death. This information is inherent in the primary tumors and in the lymph node metastases and might help to personalize patient management.

  20. Debris-flow deposits and watershed erosion rates near southern Death Valley, CA, United States

    Science.gov (United States)

    Schmidt, K.M.; Menges, C.M.; ,

    2003-01-01

    Debris flows from the steep, granitic hillslopes of the Kingston Range, CA are commensurate in age with nearby fluvial deposits. Quaternary chronostratigraphic differentiation of debris-flow deposits is based upon time-dependent characteristics such as relative boulder strength, derived from Schmidt Hammer measurements, degree of surface desert varnish, pedogenesis, and vertical separation. Rock strength is highest for Holocene-aged boulders and decreases for Pleistocene-aged boulders weathering to grus. Volumes of age-stratified debris-flow deposits, constrained by deposit thickness above bedrock, GPS surveys, and geologic mapping, are greatest for Pleistocene deposits. Shallow landslide susceptibility, derived from a topographically based GIS model, in conjunction with deposit volumes produces watershed-scale erosion rates of ???2-47 mm ka-1, with time-averaged Holocene rates exceeding Pleistocene rates. ?? 2003 Millpress.

  1. STAT3 Decoy Oligodeoxynucleotides-Loaded Solid Lipid Nanoparticles Induce Cell Death and Inhibit Invasion in Ovarian Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Yanhui Ma

    Full Text Available Recent advances in the synthesis of multi-functional nanoparticles have opened up tremendous opportunities for the targeted delivery of genes of interest. Cationic solid lipid nanoparticles (SLN can efficiently bind nucleic acid molecules and transfect genes in vitro. Few reports have combined SLN with therapy using decoy oligodeoxynucleotides (ODN. In the present study, we prepared SLN to encapsulate STAT3 decoy ODN; then, the properties and in vitro behavior of SLN-STAT3 decoy ODN complexes were investigated. SLN-STAT3 decoy ODN complexes were efficiently taken up by human ovarian cancer cells and significantly suppressed cell growth. Blockage of the STAT3 pathway by SLN-STAT3 decoy ODN complexes resulted in an evident induction of cell death, including apoptotic and autophagic death. The mechanism involved the increased expression of cleaved caspase 3, Bax, Beclin-1 and LC3-II and reduced expression of Bcl-2, pro-caspase 3, Survivin, p-Akt and p-mTOR. In addition, SLN-STAT3 decoy ODN complexes inhibited cell invasion by up-regulating E-cadherin expression and down-regulating Snail and MMP-9 expression. These findings confirmed that SLN as STAT3 decoy ODN carriers can induce cell death and inhibit invasion of ovarian cancer cells. We propose that SLN represent a potential approach for targeted gene delivery in cancer therapy.

  2. 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...

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

    Science.gov (United States)

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

    2011-12-01

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

  4. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Park, So Jung; Park, Young Jun; Shin, Ji Hyun; Kim, Eun Sung [Graduate School of East-West Medical Science, Kyung Hee University, Gyeoggi-Do 446-701 (Korea, Republic of); Hwang, Jung Jin; Jin, Dong-Hoon; Kim, Jin Cheon [Institute for Innovative Cancer Research, Asan Medical Center, Seoul 138-736 (Korea, Republic of); Cho, Dong-Hyung, E-mail: dhcho@khu.ac.kr [Graduate School of East-West Medical Science, Kyung Hee University, Gyeoggi-Do 446-701 (Korea, Republic of)

    2011-05-13

    Highlights: {yields} We screened and identified Tyrphostin A9, a receptor tyrosine kinase inhibitor as a strong mitochondria fission inducer. {yields} Tyrphostin A9 treatment promotes mitochondria dysfunction and contributes to cytotoxicity in cancer cells. {yields} Tyrphostin A9 induces apoptotic cell death through a Drp1-mediated pathway. {yields} 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.

  6. Role of solar UVB irradiance and smoking in cancer as inferred from cancer incidence rates by occupation in Nordic countries.

    Science.gov (United States)

    Grant, William B

    2012-04-01

    A large body of evidence indicates that solar ultraviolet-B (UVB) irradiance and vitamin D reduce the risk of incidence and death for many types of cancer. However, most of that evidence comes from midlatitude regions, where solar UVB doses are generally high in summer. Data on cancer standardized incidence ratios (SIRs) by sex and 54 occupation categories based on 1.4 million male and 1.36 million female cancer cases for 1961-2005 in the five Nordic countries provide the basis for an ecological study of the role of solar UVB in the risk of many types of cancer at high latitudes. Lip cancer SIRs less lung cancer SIRs for men was the best index of solar UVB dose, which was weakly inversely correlated with both melanoma and nonmelanoma skin cancer (NMSC) SIRs. Lung cancer SIRs were used as the index of the effects of smoking. For men, the UVB index was significantly inversely correlated with 14 types of internal cancer-bladder, breast, colon, gallbladder, kidney, laryngeal, liver, lung, oral, pancreatic, pharyngeal, prostate, rectal and small intestine cancer. For women, the same UVB index was inversely correlated with bladder, breast and colon cancer. These results generally agree with findings from other studies. These results provide more support for the UVB-vitamin D-cancer hypothesis and suggest that widespread fear of chronic solar ultraviolet (UV) irradiance may be misplaced.

  7. 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

  8. Human actuarial aging increases faster when background death rates are lower: a consequence of differential heterogeneity?

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    Hawkes, Kristen; Smith, Ken R; Blevins, James K

    2012-01-01

    Many analyses of human populations have found that age-specific mortality rates increase faster across most of adulthood when overall mortality levels decline. This contradicts the relationship often expected from Williams' classic hypothesis about the effects of natural selection on the evolution of senescence. More likely, much of the within-species difference in actuarial aging is not due to variation in senescence, but to the strength of filters on the heterogeneity of frailty in older survivors. A challenge to this differential frailty hypothesis was recently posed by an analysis of life tables from historical European populations and traditional societies that reported variation in actuarial aging consistent with Williams' hypothesis after all. To investigate the challenge, we reconsidered those cases and aging measures. Here we show that the discrepancy depends on Ricklefs' aging rate measure, ω, which decreases as mortality levels drop because it is an index of mortality level itself, not the rate of increase in mortality with age. We also show unappreciated correspondence among the parameters of Gompertz-Makeham and Weibull survival models. Finally, we compare the relationships among mortality parameters of the traditional societies and the historical series, providing further suggestive evidence that differential heterogeneity has strong effects on actuarial aging.

  9. Rates of 47, + 13 amd 46 translocation D/13 Patau syndrome in live births and comparison with rates in fetal deaths and at amniocentesis.

    Science.gov (United States)

    Hook, E B

    1980-11-01

    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 studies and heterogeneity in rates) is, with 95% confidence, between 4.6 X 10(-5) (1/21,700) and 14.0 X 10(-5) (1/7,000), with the most likely figure close to 8 X 10(-5) (1/12,000). Numbers are insufficient to construct a comparably narrow confidence interval for translocation cases. The rates of 47, + 13 may be estimated in (1) spontaneous abortuses, about 0.8%--1.0% (100-fold greater than in liveborns); (2) early neonatal deaths, about 0.4% (50-fold greater than in liveborns); and (3) amniocentesis, higher than in liveborns, at least for mothers 40 years and over.

  10. Brachytherapy for early oral tongue cancer: low dose rate to high dose rate.

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    Yamazaki, Hideya; Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Furukawa, Souhei; Kakimoto, Naoya; Shimizutani, Kimishige; Inoue, Toshihiko

    2003-03-01

    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.

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

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    Thomas Klein

    2015-01-01

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

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

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    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.

  13. miR-181a and miR-630 regulate cisplatin-induced cancer cell death.

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    Galluzzi, Lorenzo; Morselli, Eugenia; Vitale, Ilio; Kepp, Oliver; Senovilla, Laura; Criollo, Alfredo; Servant, Nicolas; Paccard, Caroline; Hupé, Philippe; Robert, Thomas; Ripoche, Hugues; Lazar, Vladimir; Harel-Bellan, Annick; Dessen, Philippe; Barillot, Emmanuel; Kroemer, Guido

    2010-03-01

    MicroRNAs (miRNA) are noncoding RNAs that regulate multiple cellular processes, including proliferation and apoptosis. We used microarray technology to identify miRNAs that were upregulated by non-small cell lung cancer (NSCLC) A549 cells in response to cisplatin (CDDP). The corresponding synthetic miRNA precursors (pre-miRNAs) per se were not lethal when transfected into A549 cells yet affected cell death induction by CDDP, C2-ceramide, cadmium, etoposide, and mitoxantrone in an inducer-specific fashion. Whereas synthetic miRNA inhibitors (anti-miRNAs) targeting miR-181a and miR-630 failed to modulate the response of A549 to CDDP, pre-miR-181a and pre-miR-630 enhanced and reduced CDDP-triggered cell death, respectively. Pre-miR-181a and pre-miR-630 consistently modulated mitochondrial/postmitochondrial steps of the intrinsic pathway of apoptosis, including Bax oligomerization, mitochondrial transmembrane potential dissipation, and the proteolytic maturation of caspase-9 and caspase-3. In addition, pre-miR-630 blocked early manifestations of the DNA damage response, including the phosphorylation of the ataxia-telangiectasia mutated (ATM) kinase and of two ATM substrates, histone H2AX and p53. Pharmacologic and genetic inhibition of p53 corroborated the hypothesis that pre-miR-630 (but not pre-miR-181a) blocks the upstream signaling pathways that are ignited by DNA damage and converge on p53 activation. Pre-miR-630 arrested A549 cells in the G0-G1 phase of the cell cycle, correlating with increased levels of the cell cycle inhibitor p27(Kip1) as well as with reduced proliferation rates and resulting in greatly diminished sensitivity of A549 cells to the late S-G2-M cell cycle arrest mediated by CDDP. Altogether, these results identify miR-181a and miR-630 as novel modulators of the CDDP response in NSCLC.

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

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    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.

  15. Time to biochemical recurrence after radical prostatectomy is an important predictor of clinical progression, distant metastases and cancer-specific death

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    E. I. Veliev

    2014-01-01

    Full Text Available Prostate-specific antigen is a sensitive marker for recurrent prostate cancer (PC after radical prostatectomy (RPE, which can predict thedevelopment of clinical progression and distant metastases well long before they occur. The objective of the investigation was to analyze the relationship of the time to biochemical recurrence (BCR after RPE to the development of clinical progression, distant metastases, and PC death. The vast majority (80.5 % of BCRs was common within the first 2 years after RPE and the recurrence was attended by the highest rate of clinical progression, metastases, and PC death during the first year. Correlation analysis shows that there is a statistically significant inverse correlation between the time to BCR following RPE with the development of clinical progression (rs = -0.43; p < 0.001, metastases (rs = -0.46; p < 0.001, and PC death (rs = -0.41; p < 0.001. Regardless of the time to recurrence, none of 27 patients with favorable histological characteristics (a total of post-RPE Gleason scores of ≤ 6, organ-confined disease, and a negative surgical margin developed distant metastases; only one case had a local tumor recurrence.

  16. Isolation and identification of ingredients inducing cancer cell death from the seeds of Alpinia galanga, a Chinese spice.

    Science.gov (United States)

    Zeng, Qiao-hui; Lu, Chuan-Li; Zhang, Xue-wu; Jiang, Jian-Guo

    2015-02-01

    This study was carried out to isolate ingredients from the seeds of a Chinese spice (Alpinia galangal) and to evaluate their cytotoxic activity on cancer cell lines. Isolation and purification of the phytochemical constituents were conducted using silica gel, Sephadex LH-20 and ODS columns. After extraction using 95% ethanol, the total extracts were re-extracted, resulting in petroleum ether (PE), ethyl acetate (EA) and water fractions, respectively. Activity tests showed that the EA fraction exhibited obvious (p galangal for the first time. Moreover, compounds I, II, IV and V were the main active ingredients for inducing death of the tested cancer cells, and their IC50 values ranged from 60 to 90 μg mL(-1), indicating that these compounds possessed a wide anti-cancer capability. Therefore, A. galangal seeds could be a potential source of healthy food for tumor prevention.

  17. Taking advantage: high-affinity B cells in the germinal center have lower death rates, but similar rates of division, compared to low-affinity cells.

    Science.gov (United States)

    Anderson, Shannon M; Khalil, Ashraf; Uduman, Mohamed; Hershberg, Uri; Louzoun, Yoram; Haberman, Ann M; Kleinstein, Steven H; Shlomchik, Mark J

    2009-12-01

    B lymphocytes producing high-affinity Abs are critical for protection from extracellular pathogens, such as bacteria and parasites. The process by which high-affinity B cells are selected during the immune response has never been elucidated. Although it has been shown that high-affinity cells directly outcompete low-affinity cells in the germinal center (GC), whether there are also intrinsic differences between these cells has not been addressed. It could be that higher affinity cells proliferate more rapidly or are more likely to enter cell cycle, thereby outgrowing lower affinity cells. Alternatively, higher affinity cells could be relatively more resistant to cell death in the GC. By comparing high- and low-affinity B cells for the same Ag, we show here that low-affinity cells have an intrinsically higher death rate than do cells of higher affinity, even in the absence of competition. This suggests that selection in the GC reaction is due at least in part to the control of survival of higher affinity B cells and not by a proliferative advantage conferred upon these cells compared with lower affinity B cells. Control over survival rather than proliferation of low- and high-affinity B cells in the GC allows greater diversity not only in the primary response but also in the memory response.

  18. What implementation interventions increase cancer screening rates? a systematic review

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    Lent Barbara

    2011-09-01

    Full Text Available Abstract Background Appropriate screening may reduce the mortality and morbidity of colorectal, breast, and cervical cancers. However, effective implementation strategies are warranted if the full benefits of screening are to be realized. As part of a larger agenda to create an implementation guideline, we conducted a systematic review to evaluate interventions designed to increase the rate of breast, cervical, and colorectal cancer (CRC screening. The interventions considered were: client reminders, client incentives, mass media, small media, group education, one-on-one education, reduction in structural barriers, reduction in out-of-pocket costs, provider assessment and feedback interventions, and provider incentives. Our primary outcome, screening completion, was calculated as the overall median post-intervention absolute percentage point (PP change in completed screening tests. Methods Our first step was to conduct an iterative scoping review in the research area. This yielded three relevant high-quality systematic reviews. Serving as our evidentiary foundation, we conducted a formal update. Randomized controlled trials and cluster randomized controlled trials, published between 2004 and 2010, were searched in MEDLINE, EMBASE and PSYCHinfo. Results The update yielded 66 studies new eligible studies with 74 comparisons. The new studies ranged considerably in quality. Client reminders, small media, and provider audit and feedback appear to be effective interventions to increase the uptake of screening for three cancers. One-on-one education and reduction of structural barriers also appears effective, but their roles with CRC and cervical screening, respectively, are less established. More study is required to assess client incentives, mass media, group education, reduction of out-of-pocket costs, and provider incentive interventions. Conclusion The new evidence generally aligns with the evidence and conclusions from the original systematic

  19. Comorbidity, Use of Common Medications, and Risk of Early Death in Patients with Localized or Locally Advanced Prostate Cancer

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    Carsten Nieder

    2011-01-01

    Full Text Available In this paper, we analyze predictive factors for early death from comorbidity (defined as death within 3 years from diagnosis and unrelated to prostate cancer in patients with localized or locally advanced prostate cancer. Such information may guide individually tailored treatment or observation strategies, and help to avoid overtreatment. We retrospectively analyzed baseline parameters including information on comorbidity and medication use among 177 patients (median age at diagnosis 70 years. Actuarial survival analyses were performed. During the first 3 years, two patients (1.1% died from progressive prostate cancer after they had developed distant metastases. The risk of dying from other causes (3.4% was numerically higher, although not to a statistically significant degree. Six patients who died from other causes had age-adjusted Charlson comorbidity index (CCI scores ≥5 (CCI is a sum score where each comorbid condition is assigned with a score depending on the risk of dying associated with this condition. The main comorbidity was cardiovascular disease. The two statistically significant predictive factors were medication use and age-adjusted CCI score ≥5 (univariate analysis. However, medication use was not an independent factor as all patients with age-adjusted CCI score ≥5 also used at least one class of medication. Median survival was 30 months in patients with age-adjusted CCI score ≥5. Prediction of non-prostate cancer death may be important to prevent overtreatment in patients who are more threatened by comorbidity. Our data suggest that simple parameters such as use of medications vs. none, or presence of serious cardiac disease vs. none, are not sufficient, and that age-adjusted CCI scores outperform the other factors included in our analysis.

  20. Heart rate and blood pressure in sudden unexpected death in epilepsy (SUDEP).

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    Nei, Maromi; Mintzer, Scott; Skidmore, Christopher; Sperling, Michael R; Ho, Reginald T

    2016-05-01

    Epilepsy is associated with interictal and ictal autonomic dysfunction. Seizures can immediately cause increases in blood pressure (BP) and heart rate (HR). However, it is unknown whether uncontrolled seizures, particularly when frequent, might chronically elevate the BP or HR. Additionally, it is unknown whether the interictal BP and HR is altered in individuals who are at risk for SUDEP, compared with other individuals with epilepsy. SUDEP often occurs in patients with highly refractory epilepsy. Such individuals might be at risk for a state of chronically heightened sympathetic tone, which might affect the HR and BP interictally. This study compared the resting awake interictal HR and BP in individuals who subsequently died due to SUDEP and compared these to HR and BP in two control epilepsy groups (refractory and controlled). While the overall HR and BP are similar between groups, there is a trend toward a higher diastolic BP and more stable HR in individuals who subsequently died due to SUDEP, compared with epilepsy controls. These data suggest that there may be specific types of interictal autonomic dysfunction in individuals at risk for SUDEP. Such abnormalities might serve as markers for those at elevated risk for SUDEP.

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

    Science.gov (United States)

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

    2012-05-01

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

  2. HIV infection connected to rising anal cancer rates in men in the U.S.

    Science.gov (United States)

    Human immunodeficiency virus (HIV) infection contributes substantially to the epidemic of anal cancer in men, but not women in the United States, according to new research from NCI. Chart shows overall incidence rates of anal cancers in general population

  3. Death Anxiety and Cancer-Related Stigma: A Terror Management Analysis

    Science.gov (United States)

    Mosher, Catherine E.; Danoff-Burg, Sharon

    2007-01-01

    In a study designed to examine correlates of cancer-related stigma, 405 college students were assigned randomly to listen to an audiotaped interview in which the target's cancer type and smoking status were manipulated. In the lung cancer conditions, target gender also was manipulated. Social distance and emotional responses differed according to…

  4. Novel 8-hydroxylquinoline analogs induce copper-dependent proteasome inhibition and cell death in human breast cancer cells.

    Science.gov (United States)

    Milacic, Vesna; Jiao, Peifu; Zhang, Bin; Yan, Bing; Dou, Q Ping

    2009-12-01

    An elevated level of copper (Cu), which is necessary for the growth and metastasis of tumor cells, has been found in many types of cancer, including breast, prostate, lung and brain. Although its molecular basis is unclear, this tumor-specific Cu elevation has been proposed to be a novel target for developing selective anti-cancer therapies. We previously reported that 8-hydroxylquinoline (8-OHQ) is able to form a Cu complex that inhibits the proteasome and induces apoptosis in cultured cancer cells. Toward the goal of discovering novel 8-OHQ analogs as potential anti-copper and anti-cancer drugs, in the current study we synthesized several 8-OHQ analogs and their copper complexes and evaluated their biological activities in human breast cancer cells. We report that when substitutions are made on the hydroxyl group of 8-OHQ, their copper mixtures have profound effects on the proteasome-inhibitory and apoptosis-inducing abilities in breast cancer MDA-MB-231 cells. In addition, the proteasome-inhibitory and apoptosis-inducing activities of 8-OHQ analog-copper mixtures are determined by both the polarity and position of the substituents. Finally, a synthetic complex of 8-OHQ analog-copper was able to inhibit the proteasome activity, induce cell death and suppress the growth selectively in breast cancer MDA-MB-231 cells, but not in normal immortalized human breast MCF-10A cells. Our results support the concept that human cancer cells and tissues, which contain an elevated copper level and are highly dependent on proteasome activity for their survival, should be sensitive to treatment with anti-copper drugs such as the novel 8-OHQ analogs described here.

  5. Stomach cancer incidence rates among Americans, Asian Americans and Native Asians from 1988 to 2011

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    Kim, Yeerae; Park, Jinju; Nam, Byung-Ho; Ki, Moran

    2015-01-01

    Stomach cancer is the second most common cancer in Eastern Asia, accounting for approximately 50% of all new cases of stomach cancer worldwide. Our objective was to compare the stomach cancer incidence rates of Asian Americans in Los Angeles with those of native Asians to assess the etiology of stomach cancer from 1988 to 2011. To examine these differences, Asian Americans (Korean, Japanese, Chinese, and Filipino Americans living in Los Angeles, California, USA) and native Asians (from Korea,...

  6. Induction of abscopal anti-tumor immunity and immunogenic tumor cell death by ionizing irradiation - implications for cancer therapies.

    Science.gov (United States)

    Frey, B; Rubner, Y; Wunderlich, R; Weiss, E-M; Pockley, A G; Fietkau, R; Gaipl, U S

    2012-01-01

    Although cancer progression is primarily driven by the expansion of tumor cells, the tumor microenvironment and anti-tumor immunity also play important roles. Herein, we consider how tumors can become established by escaping immune surveillance and also how cancer cells can be rendered visible to the immune system by standard therapies such as radiotherapy or chemotherapy, either alone or in combination with additional immune stimulators. Although local radiotherapy results in DNA damage (targeted effects), it is also capable of inducing immunogenic forms of tumor cell death which are associated with a release of immune activating danger signals (non-targeted effects), such as necrosis. Necrotic tumor cells may result from continued exposure to death stimuli and/or an impaired phosphatidylserine (PS) dependent clearance of the dying tumor cells. In such circumstances, mature dendritic cells take up tumor antigen and mediate the induction of adaptive and innate anti-tumor immunity. Locally-triggered, systemic immune activation can also lead to a spontaneous regression of tumors or metastases that are outside the radiation field - an effect which is termed abscopal. Preclinical studies have demonstrated that combining radiotherapy with immune stimulation can induce anti-tumor immunity. Given that it takes time for immunity to develop following exposure to immunogenic tumor cells, we propose practical combination therapies that should be considered as a basis for future research and clinical practice. It is essential that radiation oncologists become more aware of the importance of the immune system to the success of cancer therapy.

  7. 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

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    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

  8. Thymoquinone induces caspase-independent, autophagic cell death in CPT-11-resistant lovo colon cancer via mitochondrial dysfunction and activation of JNK and p38.

    Science.gov (United States)

    Chen, Ming-Cheng; Lee, Nien-Hung; Hsu, Hsi-Hsien; Ho, Tsung-Jung; Tu, Chuan-Chou; Hsieh, Dennis Jine-Yuan; Lin, Yueh-Min; Chen, Li-Mien; Kuo, Wei-Wen; Huang, Chih-Yang

    2015-02-11

    Chemotherapy causes unwanted side effects and chemoresistance, limiting its effectiveness. Therefore, phytochemicals are now used as alternative treatments. Thymoquinone (TQ) is used to treat different cancers, including colon cancer. The irinotecan-resistant (CPT-11-R) LoVo colon cancer cell line was previously constructed by stepwise CPT-11 challenges to untreated parental LoVo cells. TQ dose-dependently increased the total cell death index and activated apoptosis at 2 μM, which then diminished at increasing doses. The possibility of autophagic cell death was then investigated. TQ caused mitochondrial outer membrane permeability (MOMP) and activated autophagic cell death. JNK and p38 inhibitors (SP600125 and SB203580, respectively) reversed TQ autophagic cell death. TQ was also found to activate apoptosis before autophagy, and the direction of cell death was switched toward autophagic cell death at initiation of autophagosome formation. Therefore, TQ resulted in caspase-independent, autophagic cell death via MOMP and activation of JNK and p38 in CPT-11-R LoVo colon cancer cells.

  9. Verbal autopsy completion rate and factors associated with undetermined cause of death in a rural resource-poor setting of Tanzania

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    Maliti Deodatus V

    2011-08-01

    Full Text Available Abstract Background Verbal autopsy (VA is a widely used tool to assign probable cause of death in areas with inadequate vital registration systems. Its uses in priority setting and health planning are well documented in sub-Saharan Africa (SSA and Asia. However, there is a lack of data related to VA processing and completion rates in assigning causes of death in a community. There is also a lack of data on factors associated with undetermined causes of death documented in SSA. There is a need for such information for understanding the gaps in VA processing and better estimating disease burden. Objective The study's intent was to determine the completion rate of VA and factors associated with assigning undetermined causes of death in rural Tanzania. Methods A database of deaths reported from the Ifakara Health and Demographic Surveillance System from 2002 to 2007 was used. Completion rates were determined at the following stages of processing: 1 death identified; 2 VA interviews conducted; 3 VA forms submitted to physicians; 4 coding and assigning of cause of death. Logistic regression was used to determine factors associated with deaths coded as "undetermined." Results The completion rate of VA after identification of death and the VA interview ranged from 83% in 2002 and 89% in 2007. Ninety-four percent of deaths submitted to physicians were assigned a specific cause, with 31% of the causes coded as undetermined. Neonates and child deaths that occurred outside health facilities were associated with a high rate of undetermined classification (33%, odds ratio [OR] = 1.33, 95% confidence interval [CI] (1.05, 1.67, p = 0.016. Respondents reporting high education levels were less likely to be associated with deaths that were classified as undetermined (24%, OR = 0.76, 95% CI (0.60, -0.96, p = 0.023. Being a child of the deceased compared to a partner (husband or wife was more likely to be associated with undetermined cause of death classification

  10. Differences in Late-Stage Diagnosis, Treatment, and Colorectal Cancer-Related Death between Rural and Urban African Americans and Whites in Georgia

    Science.gov (United States)

    Hines, Robert B.; Markossian, Talar W.

    2012-01-01

    Purpose: Disparities in health outcomes due to a diagnosis of colorectal cancer (CRC) have been reported for a number of demographic groups. This study was conducted to examine the outcomes of late-stage diagnosis, treatment, and cancer-related death according to race and geographic residency status (rural vs urban). Methods: This study utilized…

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Abstract Background. With the improved prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD), causes of death and the risk of cancer might have changed. This was investigated in a Danish population with ADPKD and end-stage renal disease (ESRD) between 1 January 1993 and 31...... December 2008. Methods. Data were retrieved from three Danish national registries and a total of 823 patients were identified of which 431 had died during the study period. The 16 years were divided into two 8-year periods and the causes of death were divided into six categories: cancer, cardiovascular...... (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...

  12. Mn porphyrin in combination with ascorbate acts as a pro-oxidant and mediates caspase-independent cancer cell death.

    Science.gov (United States)

    Evans, Myron K; Tovmasyan, Artak; Batinic-Haberle, Ines; Devi, Gayathri R

    2014-03-01

    Resistance to therapy-mediated apoptosis in inflammatory breast cancer, an aggressive and distinct subtype of breast cancer, was recently attributed to increased superoxide dismutase (SOD) expression, glutathione (GSH) content, and decreased accumulation of reactive species. In this study, we demonstrate the unique ability of two Mn(III) N-substituted pyridylporphyrin (MnP)-based SOD mimics (MnTE-2-PyP(5+) and MnTnBuOE-2-PyP(5+)) to catalyze oxidation of ascorbate, leading to the production of excessive levels of peroxide, and in turn cell death. The accumulation of peroxide, as a consequence of MnP+ascorbate treatment, was fully reversed by the administration of exogenous catalase, showing that hydrogen peroxide is essential for cell death. Cell death as a consequence of the action of MnP+ascorbate corresponded to decreases in GSH levels, prosurvival signaling (p-NF-κB, p-ERK1/2), and in expression of X-linked inhibitor of apoptosis protein, the most potent caspase inhibitor. Although markers of classical apoptosis were observed, including PARP cleavage and annexin V staining, administration of a pan-caspase inhibitor, Q-VD-OPh, did not reverse the observed cytotoxicity. MnP+ascorbate-treated cells showed nuclear translocation of apoptosis-inducing factor, suggesting the possibility of a mechanism of caspase-independent cell death. Pharmacological ascorbate has already shown promise in recently completed phase I clinical trials, in which its oxidation and subsequent peroxide formation was catalyzed by endogenous metalloproteins. The catalysis of ascorbate oxidation by an optimized metal-based catalyst (such as MnP) carries a large therapeutic potential as an anticancer agent by itself or in combination with other modalities such as radio- and chemotherapy.

  13. 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

  14. Cardiac glycoside-induced cell death and Rho/Rho kinase pathway: Implication of different regulation in cancer cell lines.

    Science.gov (United States)

    Özdemir, Aysun; Şimay, Yaprak Dilber; İbişoğlu, Burçin; Yaren, Biljana; Bülbül, Döne; Ark, Mustafa

    2016-05-01

    Previously, we demonstrated that the Rho/ROCK pathway is involved in ouabain-induced apoptosis in HUVEC. In the current work, we investigated whether the Rho/ROCK pathway is functional during cardiac glycosides-induced cytotoxic effects in cancer cell lines, as well as in non-tumor cells. For that purpose, we evaluated the role of ROCK activation in bleb formation and cell migration over upstream and downstream effectors in addition to ROCK cleavage after cardiac glycosides treatment. All three cardiac glycosides (ouabain, digoxin and bufalin) induced cell death in HeLa and HepG2 cells and increased the formation of blebbing in HeLa cells. In contrast to our previous study, ROCK inhibitor Y27632 did not prevent bleb formation. Observation of ROCK II cleavage after ouabain, digoxin and oxaliplatin treatments in HeLa and/or HepG2 cells suggested that cleavage is independent of cell type and cell death induction. While inhibiting cleavage of ROCK II by the caspase inhibitors z-VAD-fmk, z-VDVAD-fmk and z-DEVD-fmk, evaluation of caspase 2 siRNA ineffectiveness on this truncation indicated that caspase-dependent ROCK II cleavage is differentially regulated in cancer cell lines. In HeLa cells, ouabain induced the activation of ROCK, although it did not induce phosphorylation of ERM, an upstream effector. While Y27632 inhibited the migration of HeLa cells, 10nM ouabain had no effect on cell migration. In conclusion, these findings indicate that the Rho/ROCK pathway is regulated differently in cancer cell lines compared to normal cells during cardiac glycosides-induced cell death.

  15. 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.

  16. Survival rate of colorectal cancer patients during 2005-2010 in Zhejiang province,China

    Institute of Scientific and Technical Information of China (English)

    罗胜兰

    2014-01-01

    Objective To analyze the survival rate of colorectal cancer,using data from the population-based cancer registry during 2005—2010 in Zhejiang.Methods The last follow-up activites on 17 235 cases regarding the survival status was December 31,2012.Both cumulative observed survival rate(OS)and relative survival rate(RS)were calculated with

  17. 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.

  18. Synthetic tambjamine analogues induce mitochondrial swelling and lysosomal dysfunction leading to autophagy blockade and necrotic cell death in lung cancer.

    Science.gov (United States)

    Rodilla, Ananda M; Korrodi-Gregório, Luís; Hernando, Elsa; Manuel-Manresa, Pilar; Quesada, Roberto; Pérez-Tomás, Ricardo; Soto-Cerrato, Vanessa

    2017-02-15

    Current pharmacological treatments for lung cancer show very poor clinical outcomes, therefore, the development of novel anticancer agents with innovative mechanisms of action is urgently needed. Cancer cells have a reversed pH gradient compared to normal cells, which favours cancer progression by promoting proliferation, metabolic adaptation and evasion of apoptosis. In this regard, the use of ionophores to modulate intracellular pH appears as a promising new therapeutic strategy. Indeed, there is a growing body of evidence supporting ionophores as novel antitumour drugs. Despite this, little is known about the implications of pH deregulation and homeostasis imbalance triggered by ionophores at the cellular level. In this work, we deeply analyse for the first time the anticancer effects of tambjamine analogues, a group of highly effective anion selective ionophores, at the cellular and molecular levels. First, their effects on cell viability were determined in several lung cancer cell lines and patient-derived cancer stem cells, demonstrating their potent cytotoxic effects. Then, we have characterized the induced lysosomal deacidification, as well as, the massive cytoplasmic vacuolization observed after treatment with these compounds, which is consistent with mitochondrial swelling. Finally, the activation of several proteins involved in stress response, autophagy and apoptosis was also detected, although they were not significantly responsible for the cell death induced. Altogether, these evidences suggest that tambjamine analogues provoke an imbalance in cellular ion homeostasis that triggers mitochondrial dysfunction and lysosomal deacidification leading to a potent cytotoxic effect through necrosis in lung cancer cell lines and cancer stem cells.

  19. Comparative analysis of cell death induction by Taurolidine in different malignant human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Ritter Peter R

    2010-03-01

    Full Text Available Abstract Background Taurolidine (TRD represents an anti-infective substance with anti-neoplastic activity in many malignant cell lines. So far, the knowledge about the cell death inducing mechanisms and pathways activated by TRD is limited. The aim of this study was therefore, to perform a comparative analysis of cell death induction by TRD simultaneously in different malignant cell lines. Materials and methods Five different malignant cell lines (HT29/Colon, Chang Liver/Liver, HT1080/fibrosarcoma, AsPC-1/pancreas and BxPC-3/pancreas were incubated with increasing concentrations of TRD (100 μM, 250 μM and 1000 μM for 6 h and 24 h. Cell viability, apoptosis and necrosis were analyzed by FACS analysis (Propidiumiodide/AnnexinV staining. Additionally, cells were co-incubated with the caspase Inhibitor z-VAD, the radical scavenger N-Acetylcystein (NAC and the Gluthation depleting agent BSO to examine the contribution of caspase activation and reactive oxygen species in TRD induced cell death. Results All cell lines were susceptible to TRD induced cell death without resistance toward this anti-neoplastic agent. However, the dose response effects were varying largely between different cell lines. The effect of NAC and BSO co-treatment were highly different among cell lines - suggesting a cell line specific involvement of ROS in TRD induced cell death. Furthermore, impact of z-VAD mediated inhibition of caspases was differing strongly among the cell lines. Conclusion This is the first study providing a simultaneous evaluation of the anti-neoplastic action of TRD across several malignant cell lines. The involvement of ROS and caspase activation was highly variable among the five cell lines, although all were susceptible to TRD induced cell death. Our results indicate, that TRD is likely to provide multifaceted cell death mechanisms leading to a cell line specific diversity.

  20. Vitamin B₂ Sensitizes Cancer Cells to Vitamin-C-Induced Cell Death via Modulation of Akt and Bad Phosphorylation.

    Science.gov (United States)

    Chen, Ni; Yin, Shutao; Song, Xinhua; Fan, Lihong; Hu, Hongbo

    2015-08-01

    Vitamin C is an essential dietary nutrient that has a variety of biological functions. Recent studies have provided promising evidence for its additional health benefits, including anticancer activity. Vitamin B2, another essential dietary nutrient, often coexists with vitamin C in some fruits, vegetables, or dietary supplements. The objective of the present study is to determine whether the combination of vitamin C and B2 can achieve a synergistic anticancer activity. MDA-MB-231, MCF-7, and A549 cells were employed to evaluate the combinatory effects of vitamin C and B2. We found that the combination of vitamin C and B2 resulted in a synergistic cell death induction in all cell lines tested. Further mechanistic investigations revealed that vitamin B2 sensitized cancer cells to vitamin C through inhibition of Akt and Bad phosphorylation. Our findings identified vitamin B2 as a promising sensitizer for improving the efficacy of vitamin-C-based cancer chemoprevention and chemotherapy.

  1. 1973-2010年常熟市居民胃癌死亡及减寿情况%Analysis on death and life lost from gastric cancer among residents in Changshu City from 1973-2010

    Institute of Scientific and Technical Information of China (English)

    徐晓燕; 周正元; 张宁

    2013-01-01

    [Objective]To analyze the status of death and life lost from gastric cancer among residents in Changshu City from 1973-2010, provide the basis for making the control measures of gastric cancer. [ Methods ] The data of death from gastric cancer in Changshu City from 1973-2010 were collected to calculate mortality and life lost rate, and its changes with time were observed. [ Results] The crude death rate of gastric cancer among residents in Changshu City from 1973-2010 was 47.91/lakh, and the standardized mortality rate was 34. 79/lakh, which accounted for 26. 73% of death caused by malignant tumor. The mortality rates of gastric cancer in males and females increased significantly with increasing age. The mortality, standardized mortality rate and life lost rate of gastric cancer in males were higher than those in females. As time goes on, the standardized mortality rate of gastric cancer showed a downward trend. [ Conclusion ] The gastric cancer severely impairs the health of residents in Changshu City. The aged tendency of population is the main factor of higher crude death rate of gastric cancer, meanwhile, unhealthy diet habit, long-term chronic gastritis, lack of early detection and timely treatment are the important influencing factors. In is necessary to cany out comprehensive intervention measures to control and reduce the gastric cancer.%目的 对1973-2010年常熟市居民胃癌死亡及减寿情况进行分析,为制定胃癌防治措施提供依据.方法 采用常熟市1973-2010年的胃癌死亡数据,计算其死亡率与减寿率,并观察其随时间的变化情况.结果 1973-2010年常熟市居民胃癌粗死亡率为47.91/10万,标化死亡率为34.79/10万,占恶性肿瘤死亡的26.73%.随着年龄的增长,男女性的胃癌死亡率都呈显著上升趋势,男性胃癌死亡率、标化死亡率、减寿率均高于女性.随着时间的推移,胃癌的标化死亡率呈不断下降趋势.结论 胃癌对该市居民健康危害较大,人

  2. 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.

  3. 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).

  4. The Nuclear Death Domain Protein p84N5; A Candidate Breast Cancer Susceptibility Gene

    Science.gov (United States)

    2007-05-01

    maintained in RPMI supplemented with 10% FBS and 0.2 unit/mL of pork insulin. SKBP-3 cells were maintained in McCoy’s 5a medium supplemented with 15... Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long term

  5. The combined effect of cancer and chronic diseases on general practitioner consultation rates.

    NARCIS (Netherlands)

    Heins, M.J.; Korevaar, J.C.; Donker, G.A.; Rijken, P.M.; Schellevis, F.G.

    2015-01-01

    Aim: More than two-thirds of cancer patients have one or more chronic diseases besides cancer. The purpose of this study was to get detailed insight into the combined effect of cancer and chronic diseases on general practitioner (GP) consultation rates. Methods: From the NIVEL Primary Care Database

  6. Living with Cancer

    Institute of Scientific and Technical Information of China (English)

    1996-01-01

    Cancer is regarded as a formidable threat to mankind. Every yem’ in Shanghai, which has a high cancer rate, 15,000 people are diagnosed with the disease and 12,000 die of cancer. Because many people believe that "cancer equals death," a special cancer rehabilitation center has appeared in Shanghai. The center creates an environment where cancer patients can exchange experiences and receive psychological group therapy. In this way those patients

  7. Health Information Seeking and Cancer Screening Adherence Rates.

    Science.gov (United States)

    Shneyderman, Yuliya; Rutten, Lila J Finney; Arheart, Kristopher L; Byrne, Margaret M; Kornfeld, Julie; Schwartz, Seth J

    2016-03-01

    Effective screening tools are available for many of the top cancer killers in the USA. Searching for health information has previously been found to be associated with adhering to cancer screening guidelines, but Internet information seeking has not been examined separately. The current study examines the relationship between health and cancer Internet information seeking and adherence to cancer screening guidelines for breast, cervical, and colorectal cancer in a large nationally representative dataset. The current study was conducted using data from the Health Information National Trends Survey from 2003 and 2007. The study examined age-stratified models which correlated health and cancer information seeking with getting breast, cervical, and colorectal cancer screening on schedule, while controlling for several key variables. Internet health and cancer information seeking was positively associated with getting Pap screening on schedule, while information seeking from any sources was positively associated with getting colorectal screening on schedule. People who look for health or cancer information are more likely to get screened on schedule. Some groups of people, however, do not exhibit this relationship and, thus, may be more vulnerable to under-screening. These groups may benefit more from targeted interventions that attempt to engage people in their health care more actively.

  8. Synergistic enhancement of breast cancer cell death using ultrasound-microbubbles in combination with cisplatin

    Science.gov (United States)

    Jetha, Sheliza; Karshafian, Raffi

    2017-03-01

    Cisplatin (CDDP), an anti-cancer agent, can effectively treat several cancerous tumourstumors such as testicular, bladder, and ovarian cancers. CDDP binds to specific DNA bases causing 1,2-intrastrand cross-links, single strand and double strand breaks inducing apoptosis. However, the effectiveness of CDDP is limited in tumourtumors such as breast cancer due to drug resistance. In this study, the application of ultrasound-microbubble (USMB) in improving the therapeutic effect of CDDP in breast cancer cell line is investigated. Human breast cancer (MDA-MB-231) cells in suspension (2×106 cells/mL concentration and 0.6 mL volume) were treated with CDDP (3 µM, 30 µM and 300 µM) and USMB at 0.5 MHz pulse centered frequency, 60 s insonation time, 16 µs pulse duration, 1 kHz pulse repetition frequency, and 1.7% v/v (volume concentration) of Definity microbubble agent. Following USMB treatment, cells were plated in 96-well plates for 24 and 48-hour incubation, after which cell viability was measured using MTT assay (VMTT). Cell viability decreased significantly with the combined treatment of CDDP and USMB compared to CDDP alone (pcancer cells. However, this enhanced effectiveness, in breast cancer cells (MDA-MB-231), is dependent on incubation time and cisplatin (CDDP) concentration.

  9. Life and Death Decision Analysis.

    Science.gov (United States)

    1979-12-01

    LIFE SMOKING: CANCER, EMPHYSEMA, SHORTENED LIFE BATHING: FALLING, ELECTROCUTION CONTRACEPTION: DEATH , ILLNESS PREGNANCY: DEATH , ILLNESS ABORTION ...economic effect is the one with the highest probability of causing my death . -13- EXPECTED NET SYSTEM DESIGN BENEFIT TO ME DEATH DEATH (r A(excluding death ...0-AO81 424 STANFORD UNIV CALIF DEPT OF ENGtNEERING-ECONOM!C SYSTEMS F/6 12/1 LIFE ANDI DEATH DECISION ANALYSIS.CU) DEC 79 R A HOWARD N0OOIN-79-C-0036

  10. Postoperative medical complications are the main cause of early death after emergency surgery for colonic cancer

    DEFF Research Database (Denmark)

    Iversen, L.H.; Bulow, S.; Christensen, Ib Jarle

    2008-01-01

    . The strongest risk factor for early death was postoperative medical complications (cardiopulmonary, renal, thromboembolic and infectious), with an odds ratio of 11.7 (95 percent confidence interval 8.8 to 15.5). Such complications occurred in 24.4 per cent of patients, of whom 57.8 per cent died. Other...

  11. ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death

    NARCIS (Netherlands)

    Garg, A.D.; Dudek, A.M.D.; Ferreira, G.B.; Verfaillie, T.; Vandenabeele, P.; Krysko, D.V.; Mathieu, C.; Agostinis, P.

    2013-01-01

    Calreticulin surface exposure (ecto-CALR), ATP secretion, maturation of dendritic cells (DCs) and stimulation of T cells are prerequisites for anticancer therapy-induced immunogenic cell death (ICD). Recent evidence suggests that chemotherapy-induced autophagy may positively regulate ICD by favoring

  12. Characterization of Breast Cancer Cell Death Induced by Interferons and Retinoids

    Science.gov (United States)

    1999-07-01

    Bioi.. activity, which also reached its maximum during cell death. WEHI cells (2), it inhibited the growth of certain hepatoma Thus, there appears...culture flask generally chains oflgA and IgG, correlating with IgA and IgG deficiency previoulsy showed much lower cyclins as well as CKI levels than the

  13. 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.

  14. Metabolic rates of ATP transfer through creatine kinase (CK Flux) predict clinical heart failure events and death.

    Science.gov (United States)

    Bottomley, Paul A; Panjrath, Gurusher S; Lai, Shenghan; Hirsch, Glenn A; Wu, Katherine; Najjar, Samer S; Steinberg, Angela; Gerstenblith, Gary; Weiss, Robert G

    2013-12-11

    Morbidity and mortality from heart failure (HF) are high, and current risk stratification approaches for predicting HF progression are imperfect. Adenosine triphosphate (ATP) is required for normal cardiac contraction, and abnormalities in creatine kinase (CK) energy metabolism, the primary myocardial energy reserve reaction, have been observed in experimental and clinical HF. However, the prognostic value of abnormalities in ATP production rates through CK in human HF has not been investigated. Fifty-eight HF patients with nonischemic cardiomyopathy underwent ³¹P magnetic resonance spectroscopy (MRS) to quantify cardiac high-energy phosphates and the rate of ATP synthesis through CK (CK flux) and were prospectively followed for a median of 4.7 years. Multiple-event analysis (MEA) was performed for HF-related events including all-cause and cardiac death, HF hospitalization, cardiac transplantation, and ventricular-assist device placement. Among baseline demographic, clinical, and metabolic parameters, MEA identified four independent predictors of HF events: New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), African-American race, and CK flux. Reduced myocardial CK flux was a significant predictor of HF outcomes, even after correction for NYHA class, LVEF, and race. For each increase in CK flux of 1 μmol g⁻¹ s⁻¹, risk of HF-related composite outcomes decreased by 32 to 39%. These findings suggest that reduced CK flux may be a potential HF treatment target. Newer imaging strategies, including noninvasive ³¹P MRS that detect altered ATP kinetics, could thus complement risk stratification in HF and add value in conditions involving other tissues with high energy demands, including skeletal muscle and brain.

  15. County-level socioeconomic status and cancer rates in Texas, 2001-2005.

    Science.gov (United States)

    Risser, David R; Miller, Eric A; Williams, Melanie A; Foxhall, Lewis E

    2010-10-01

    Previous studies have shown that a person's socioeconomic status (SES) (a proxy measure that can incorporate income, wealth, education, and occupation) is associated with cancer incidence and mortality. Examining variation in cancer rates by SES can help identify health disparities and target areas for cancer control activities. The Texas Cancer Registry (TCR) collects data on every newly diagnosed case of cancer in Texas, including personal and demographic data, but does not collect data related directly to SES. Using a county-level measure of SES determined by the 2000 US Census, we compared cancer incidence and mortality rates for selected cancer sites by counties categorized into Low, Intermediate, and High SES. The cancers examined in this analysis included lung, colorectal, female breast, prostate, cervical, and all cancers collected by TCR combined. Consistent with other studies, most incidence and mortality rates were lowest in the High SES counties. However, in general, the highest incidence and mortality rates were found in counties categorized as Intermediate SES, but patterns differed by cancer site and by race and ethnicity. This study provides additional evidence that geographically related SES is associated with cancer incidence and mortality.

  16. Incident Diagnoses of Cancers and Cancer-related Deaths, Active Component, U.S. Armed Forces, 2000-2011

    Science.gov (United States)

    2012-06-01

    this report. Active military populations diff er from the U.S. civilian population in many ways. Several factors that diff er in the pop- ulations... factors are associated with cancer risk including tobacco use, food and alcohol consump- tion, physical activity, medication use, his- tory of...cancer screening exami- nations such as mammography, prostate specifi c antigen (PSA) testing, cytological examination of the cervix ( Papanicolaou

  17. Glucose starvation-mediated inhibition of salinomycin induced autophagy amplifies cancer cell specific cell death

    OpenAIRE

    Jangamreddy, Jaganmohan R.; Jain, Mayur V.; Hallbeck, Anna-Lotta; Roberg, Karin; Lotfi, Kourosh; Łos, Marek J.

    2015-01-01

    Salinomycin has been used as treatment for malignant tumors in a small number of humans, causing far less side effects than standard chemotherapy. Several studies show that Salinomycin targets cancer-initiating cells (cancer stem cells, or CSC) resistant to conventional therapies. Numerous studies show that Salinomycin not only reduces tumor volume, but also decreases tumor recurrence when used as an adjuvant to standard treatments. In this study we show that starvation triggered different st...

  18. In vitro study of cell death with 5-aminolevulinic acid based photodynamic therapy to improve the efficiency of cancer treatment

    Science.gov (United States)

    Firdous, S.; Nawaz, M.; Ikram, M.; Ahmed, M.

    2012-03-01

    Photodynamic therapy (PDT) is a kind of photochemo therapeutic treatment that exerts its effect mainly through the induction of cell death. Distinct types of cell death may be elicited by different PDT regimes. In this study, efforts are underway to optimize PDT protocols for improved efficacy and combination of all three PDT mechanisms involved in the different human carcinomas cell narcosis. Our in vitro cell culture experiments with 5-aminolevulanic acid (ALA) a clinically approved photiosensitizer (PS) and 635 nm laser light have yielded promising results, as follow: (1) (human cervical cancer (HeLa) cell line incubated, for 18 h, with 30 μg/ml of 5-ALA, treated with laser light dose of 50 J/cm2 can produce 85% of cell killing (2) human larynx carcinoma (Hep2c) cell line incubated, for 7 h, with 55 μg/ml of 5-ALA, treated with laser light dose of 85 J/cm2 can produce 75% of cell killing (3) human liver cancer (HepG2) cell line incubated, for 22-48 h, with 262 μg/ml of 5-ALA, treated with laser light dose of 120 J/cm2 can produce 95% of cell killing (4) human muscle cancer (RD) cell line incubated, for 47 h, with 250 μg/ml of 5-ALA, treated with laser light dose of 80 J/cm2 can produce 76% of cell killing (5) Human embryonic kidney (HEK293T) cell line incu-bated, for 18 h, with 400 μg/ml of 5-ALA, treated with laser light dose of 40 J/cm2 can produce 82% of cell killing confirming the efficacy of photodynamic therapy.

  19. Cancer incidence rates in the Kurdistan region/Iraq from 2007-2009.

    Science.gov (United States)

    Othman, Ramadhan T; Abdulljabar, Rezvan; Saeed, Abdullah; Kittani, Sarwar Sadiq; Sulaiman, Hushyar M; Mohammed, Sami A; Rashid, Rekawt M; Hussein, Nawfal R

    2011-01-01

    Cancer is a disease of gradual increase in incidence overall the world. Kurdistan Region in Iraq has been exposed to several carcinogenic hazards. There are few reports about the increased risk of cancer in different cities in Iraq. These reports did not cover Kurdistan region. The aim of this paper was to study cancer incidence and to identify possible risks of cancer in this region. Cancer registries from 9 hospitals in three cities of Kurdistan were used as a source of data. Information on these cases was subjected to careful verification regarding repetition, place of residence and other possible errors. Overall registered cases in 2007, 2008 and 2009 were 1444, 2081, 2356 respectively. 49% of registered cases were males and 51% were female. The Age Standardized Rate of cancer was 89.83/100 000 among male and 83.93/100 000 among female. The results showed major variation in incidence rates of different types of cancer in the three governorates of Kurdistan. Furthermore, there was evidence of increased risks of cancer in Kurdistan Region in Iraq. Hematological malignancies were the most common cancer among male (21.13% of all cancer in males) and second most common in female (18.8% of all cancer in female), only exceeded by breast cancer. To reach sound conclusions about extent and determinants of cancer in Kurdistan, enormous multi-spectrum efforts are now needed.

  20. Salinomycin induces cell death with autophagy through activation of endoplasmic reticulum stress in human cancer cells.

    Science.gov (United States)

    Li, Tianliang; Su, Ling; Zhong, Ning; Hao, Xuexi; Zhong, Diansheng; Singhal, Sunil; Liu, Xiangguo

    2013-07-01

    Salinomycin is perhaps the first promising compound that was discovered through high throughput screening in cancer stem cells. This novel agent can selectively eliminate breast and other cancer stem cells, though the mechanism of action remains unclear. In this study, we found that salinomycin induced autophagy in human non-small cell lung cancer (NSCLC) cells. Furthermore, we demonstrated that salinomycin stimulated endoplasmic reticulum stress and mediated autophagy via the ATF4-DDIT3/CHOP-TRIB3-AKT1-MTOR axis. Moreover, we found that the autophagy induced by salinomycin played a prosurvival role in human NSCLC cells and attenuated the apoptotic cascade. We also showed that salinomycin triggered more apoptosis and less autophagy in A549 cells in which CDH1 expression was inhibited, suggesting that the inhibition of autophagy might represent a promising strategy to target cancer stem cells. In conclusion, these findings provide evidence that combination treatment with salinomycin and pharmacological autophagy inhibitors will be an effective therapeutic strategy for eliminating cancer cells as well as cancer stem cells.

  1. Statistical analysis of the maternal death rate at the Ebonyi State University Teaching Hospital, Abakaliki, for the year ending 31 December 2007

    Directory of Open Access Journals (Sweden)

    Uchechukwu M. Okeh

    2009-04-01

    Full Text Available Background: The maternal mortality rate in developing countries, such as Nigeria, remains relatively high, with the causes being multidimensional. The unbooked primigravidae with severe pre-eclampsia/eclampsia constitute a high risk group.Method: The data from the case notes of all the maternal deaths that occurred at the Ebonyi State University Teaching Hospital, Abakaliki, between 1 January and 31 December 2007 form the basis of this study. The case notes relating to all such deaths were stored in the office of the Head of the Department of Obstetrics and Gynaecology when the deaths occurred. Information was extracted from the case files at the end of 2007. Data relating to the total number of deliveries were obtained from the registers kept in the labour and isolation wards.Results: Of the 45 maternal deaths recorded, 40 (88.9% were found to have occurred among the unbooked and 5 (11% among the booked mothers, constituting a maternal mortality ratio (MMR of 23 121.4 and 339.7 per 100 000 deliveries respectively. The combined mortality ratio was 2 735.6 per 100 000 deliveries. Fifteen (37.5% unbooked primigravidae were found to have died of severe pre-eclampsia/eclampsia. A total of 1 645 mothers were noted to have delivered babies, of whom 1 472(89.5% were booked, and 173 (10.5% unbooked, with the hospital.Conclusion: Severe pre-eclampsia/eclampsia, haemorrhaging and sepsis were the major causes of death. A high maternal mortality rate was found to be common among the unbooked primigravidae, who are known usually to present late with pre-eclampsia/eclampsia. More research into the causes and management of pre-eclampsia/eclampsia is needed to reduce the high maternal death rate associated with it. The lack of antenatal care is also a high risk factor for maternal death.

  2. Pharmacoproteomic study of the natural product Ebenfuran III in DU-145 prostate cancer cells: the quantitative and temporal interrogation of chemically induced cell death at the protein level.

    Science.gov (United States)

    Roumeliotis, Theodoros I; Halabalaki, Maria; Alexi, Xanthippi; Ankrett, Dyan; Giannopoulou, Eugenia G; Skaltsounis, Alexios-Leandros; Sayan, Berna S; Alexis, Michael N; Townsend, Paul A; Garbis, Spiros D

    2013-04-05

    A naturally occurring benzofuran derivative, Ebenfuran III (Eb III), was investigated for its antiproliferative effects using the DU-145 prostate cell line. Eb III was isolated from Onobrychis ebenoides of the Leguminosae family, a plant endemic in Central and Southern Greece. We have previously reported that Eb III exerts significant cytotoxic effects on certain cancer cell lines. This effect is thought to occur via the isoprenyl moiety at the C-5 position of the molecule. The study aim was to gain a deeper understanding of the pharmacological effect of Eb III on DU-145 cell death at the translational level using a relative quantitative and temporal proteomics approach. Proteins extracted from the cell pellets were subjected to solution phase trypsin proteolysis followed by iTRAQ-labeling. The labeled tryptic peptide extracts were then fractionated using strong cation exchange chromatography and the fractions were analyzed by nanoflow reverse phase ultraperformance liquid chromatography-nanoelectrospray ionization-tandem mass spectrometry analysis using a hybrid QqTOF platform. Using this approach, we compared the expression levels of 1360 proteins analyzed at ≤ 1% global protein false discovery rate (FDR), commonly present in untreated (control, vehicle only) and Eb III-treated cells at the different exposure time points. Through the iterative use of Ingenuity Pathway Analysis with hierarchical clustering of protein expression patterns, followed by bibliographic research, the temporal regulation of the Calpain-1, ERK2, PAR-4, RAB-7, and Bap31 proteins were identified as potential nodes of multipathway convergence to Eb III induced DU-145 cell death. These proteins were further verified with Western blot analysis. This gel-free, quantitative 2DLC-MS/MS proteomics method effectively captured novel modulated proteins in the DU-145 cell line as a response to Eb III treatment. This approach also provided greater insight to the multifocal and combinatorial signaling

  3. Preferences Regarding Return of Genomic Results to Relatives of Research Participants, Including after Participant Death: Empirical Results from a Cancer Biobank.

    Science.gov (United States)

    Breitkopf, Carmen Radecki; Petersen, Gloria M; Wolf, Susan M; Chaffee, Kari G; Robinson, Marguerite E; Gordon, Deborah R; Lindor, Noralane M; Koenig, Barbara A

    2015-01-01

    Data are lacking with regard to participants' perspectives on return of genetic research results to relatives, including after the participant's death. This paper reports descriptive results from 3,630 survey respondents: 464 participants in a pancreatic cancer biobank, 1,439 family registry participants, and 1,727 healthy individuals. Our findings indicate that most participants would feel obligated to share their results with blood relatives while alive and would want results to be shared with relatives after their death.

  4. 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

  5. Adult stromal cells derived from human adipose tissue provoke pancreatic cancer cell death both in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Beatrice Cousin

    Full Text Available BACKGROUND: Normal tissue homeostasis is maintained by dynamic interactions between epithelial cells and their microenvironment. Disrupting this homeostasis can induce aberrant cell proliferation, adhesion, function and migration that might promote malignant behavior. Indeed, aberrant stromal-epithelial interactions contribute to pancreatic ductal adenocarcinoma (PDAC spread and metastasis, and this raises the possibility that novel stroma-targeted therapies represent additional approaches for combating this malignant disease. The aim of the present study was to determine the effect of human stromal cells derived from adipose tissue (ADSC on pancreatic tumor cell proliferation. PRINCIPAL FINDINGS: Co-culturing pancreatic tumor cells with ADSC and ADSC-conditioned medium sampled from different donors inhibited cancer cell viability and proliferation. ADSC-mediated inhibitory effect was further extended to other epithelial cancer-derived cell lines (liver, colon, prostate. ADSC conditioned medium induced cancer cell necrosis following G1-phase arrest, without evidence of apoptosis. In vivo, a single intra-tumoral injection of ADSC in a model of pancreatic adenocarcinoma induced a strong and long-lasting inhibition of tumor growth. CONCLUSION: These data indicate that ADSC strongly inhibit PDAC proliferation, both in vitro and in vivo and induce tumor cell death by altering cell cycle progression. Therefore, ADSC may constitute a potential cell-based therapeutic alternative for the treatment of PDAC for which no effective cure is available.

  6. Myeloid zinc finger 1 mediates sulindac sulfide-induced upregulation of death receptor 5 of human colon cancer cells.

    Science.gov (United States)

    Horinaka, Mano; Yoshida, Tatsushi; Tomosugi, Mitsuhiro; Yasuda, Shusuke; Sowa, Yoshihiro; Sakai, Toshiyuki

    2014-08-08

    A combined therapy of sulindac sulfide and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising strategy for the treatment of cancer. Sulindac sulfide had been shown to induce the expression of death receptor 5 (DR5), a receptor for TRAIL, and sensitize cancer cells to TRAIL-induced apoptosis; however, the molecular mechanism underlying the upregulation of DR5 has not yet been elucidated. We demonstrate here that myeloid zinc finger 1 (MZF1) mediates the induction of DR5 by sulindac sulfide. Sulindac sulfide induced the expression of DR5 at the protein and mRNA levels in colon cancer SW480 cells. Furthermore, sulindac sulfide increased DR5 promoter activity. We showed that sulindac sulfide stimulated DR5 promoter activity via the -301 to -253 region. This region contained a putative MZF1-binding site. Site-directed mutations in the site abrogated the enhancement in DR5 promoter activity by sulindac sulfide. MZF1 directly bound to the putative MZF1-binding site of the DR5 promoter and the binding was increased by sulindac sulfide. The expression of MZF1 was also increased by sulindac sulfide, and MZF1 siRNA attenuated the upregulation of DR5 by sulindac sulfide. These results indicate that sulindac sulfide induces the expression of DR5 by up-regulating MZF1.

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

    Science.gov (United States)

    Lin, Jiong; Lin, Yao; Fan, Li; Kuang, Wei; Zheng, Liwei; Wu, Jiahua; Shang, Peng; Wang, Qiaofeng; Tan, Jiali

    2016-04-29

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

  8. Updated Death and Injury Rates of U.S. Military Personnel During the Conflicts in Iraq and Afghanistan

    Science.gov (United States)

    2014-12-01

    Killed-in-action ( KIA ): those who die immediately on the battlefield; • Died-of-wounds (DOW): those who survive injury on the battlefield, but...initial hospital admission.5 KIA and DOW are often combined as hostile deaths, and I will do so henceforth. DoD also reports non-hostile deaths...seasonal basis. In my earlier paper I estimated the size of the surge in Iraq at 37,000 troops. I estimated the hostile death (combining KIAs and DOWs

  9. Induction of morphological changes in death-induced cancer cells monitored by holographic microscopy.

    Science.gov (United States)

    El-Schich, Zahra; Mölder, Anna; Tassidis, Helena; Härkönen, Pirkko; Falck Miniotis, Maria; Gjörloff Wingren, Anette

    2015-03-01

    We are using the label-free technique of holographic microscopy to analyze cellular parameters including cell number, confluence, cellular volume and area directly in the cell culture environment. We show that death-induced cells can be distinguished from untreated counterparts by the use of holographic microscopy, and we demonstrate its capability for cell death assessment. Morphological analysis of two representative cell lines (L929 and DU145) was performed in the culture flasks without any prior cell detachment. The two cell lines were treated with the anti-tumour agent etoposide for 1-3days. Measurements by holographic microscopy showed significant differences in average cell number, confluence, volume and area when comparing etoposide-treated with untreated cells. The cell volume of the treated cell lines was initially increased at early time-points. By time, cells decreased in volume, especially when treated with high doses of etoposide. In conclusion, we have shown that holographic microscopy allows label-free and completely non-invasive morphological measurements of cell growth, viability and death. Future applications could include real-time monitoring of these holographic microscopy parameters in cells in response to clinically relevant compounds.

  10. Antiviral signaling protein MITA acts as a tumor suppressor in breast cancer by regulating NF-κB induced cell death.

    Science.gov (United States)

    Bhatelia, Khyati; Singh, Aru; Tomar, Dhanendra; Singh, Kritarth; Sripada, Lakshmi; Chagtoo, Megha; Prajapati, Paresh; Singh, Rochika; Godbole, Madan M; Singh, Rajesh

    2014-02-01

    Emerging evidences suggest that chronic inflammation is one of the major causes of tumorigenesis. The role of inflammation in regulation of breast cancer progression is not well established. Recently Mediator of IRF3 Activation (MITA) protein has been identified that regulates NF-κB and IFN pathways. Role of MITA in the context of inflammation and cancer progression has not been investigated. In the current report, we studied the role of MITA in the regulation of cross talk between cell death and inflammation in breast cancer cells. The expression of MITA was significantly lower on in estrogen receptor (ER) positive breast cancer cells than ER negative cells. Similarly, it was significantly down regulated in tumor tissue as compared to the normal tissue. The overexpression of MITA in MCF-7 and T47D decreases the cell proliferation and increases the cell death by activation of caspases. MITA positively regulates NF-κB transcription factor, which is essential for MITA induced cell death. The activation of NF-κB induces TNF-α production which further sensitizes MITA induced cell death by activation of death receptor pathway through capsase-8. MITA expression decreases the colony forming units and migration ability of MCF-7 cells. Thus, our finding suggests that MITA acts as a tumor suppressor which is down regulated during tumorigenesis providing survival advantage to tumor cell.

  11. Multimodal Superparamagnetic Nanoparticles with Unusually Enhanced Specific Absorption Rate for Synergetic Cancer Therapeutics and Magnetic Resonance Imaging.

    Science.gov (United States)

    Thorat, Nanasaheb D; Bohara, Raghvendra A; Malgras, Victor; Tofail, Syed A M; Ahamad, Tansir; Alshehri, Saad M; Wu, Kevin C-W; Yamauchi, Yusuke

    2016-06-15

    Superparamagnetic nanoparticles (SPMNPs) used for magnetic resonance imaging (MRI) and magnetic fluid hyperthermia (MFH) cancer therapy frequently face trade off between a high magnetization saturation and their good colloidal stability, high specific absorption rate (SAR), and most importantly biological compatibility. This necessitates the development of new nanomaterials, as MFH and MRI are considered to be one of the most promising combined noninvasive treatments. In the present study, we investigated polyethylene glycol (PEG) functionalized La1-xSrxMnO3 (LSMO) SPMNPs for efficient cancer hyperthermia therapy and MRI application. The superparamagnetic nanomaterial revealed excellent colloidal stability and biocompatibility. A high SAR of 390 W/g was observed due to higher colloidal stability leading to an increased Brownian and Neel's spin relaxation. Cell viability of PEG capped nanoparticles is up to 80% on different cell lines tested rigorously using different methods. PEG coating provided excellent hemocompatibility to human red blood cells as PEG functionalized SPMNPs reduced hemolysis efficiently compared to its uncoated counterpart. Magnetic fluid hyperthermia of SPMNPs resulted in cancer cell death up to 80%. Additionally, improved MRI characteristics were also observed for the PEG capped La1-xSrxMnO3 formulation in aqueous medium compared to the bare LSMO. Taken together, PEG capped SPMNPs can be useful for diagnosis, efficient magnetic fluid hyperthermia, and multimodal cancer treatment as the amphiphilicity of PEG can easily be utilized to encapsulate hydrophobic drugs.

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

    Science.gov (United States)

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

    2005-11-01

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

  13. 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.

  14. Stomach cancer incidence rates among Americans, Asian Americans and Native Asians from 1988 to 2011.

    Science.gov (United States)

    Kim, Yeerae; Park, Jinju; Nam, Byung-Ho; Ki, Moran

    2015-01-01

    Stomach cancer is the second most common cancer in Eastern Asia, accounting for approximately 50% of all new cases of stomach cancer worldwide. Our objective was to compare the stomach cancer incidence rates of Asian Americans in Los Angeles with those of native Asians to assess the etiology of stomach cancer from 1988 to 2011. To examine these differences, Asian Americans (Korean, Japanese, Chinese, and Filipino Americans living in Los Angeles, California, USA) and native Asians (from Korea, Japan, China, and the Philippines) were selected for this study. Using the Cancer Incidence in Five Continents database, stomach cancer incidence rates were examined. Data from the National Cancer Registry of Korea were used for native Koreans. Between native countries, the incidence rates in Japan, China, the Philippines, and the US declined over time, but the incidence in Korea has remained constant. The incidences among Asian immigrants were lower than those among native Asians. The incidence rates of males were approximately 2 times higher than those among females in Asian countries were. The effect of immigration on stomach cancer incidence suggests that lifestyle factors are a significant determinant of stomach cancer risk. However, the incidence in Korea remains the highest of these countries.

  15. Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and progression

    Science.gov (United States)

    Lee, Jong Hun; Khor, Tin Oo; Shu, Limin; Su, Zheng-Yuan; Fuentes, Francisco; Kong, Ah-Ng Tony

    2013-01-01

    Reactive metabolites from carcinogens and oxidative stress can drive genetic mutations, genomic instability, neoplastic transformation, and ultimately carcinogenesis. Numerous dietary phytochemicals in vegetables/fruits have been shown to possess cancer chemopreventive effects in both preclinical animal models and human epidemiological studies. These phytochemicals could prevent the initiation of carcinogenesis via either direct scavenging of reactive oxygen species/reactive nitrogen species (ROS/RNS) or, more importantly, the induction of cellular defense detoxifying/antioxidant enzymes. These defense enzymes mediated by Nrf2-antioxidative stress and anti-inflammatory signaling pathways can contribute to cellular protection against ROS/RNS and reactive metabolites of carcinogens. In addition, these compounds would kill initiated/transformed cancer cells in vitro and in in vivo xenografts via diverse anti-cancer mechanisms. These mechanisms include the activation of signaling kinases (e.g., JNK), caspases and the mitochondria damage/cytochrome c pathways. Phytochemicals may also have anti-cancer effects by inhibiting the IKK/NF-κB pathway, inhibiting STAT3, and causing cell cycle arrest. In addition, other mechanisms may include epigenetic alterations (e.g., inhibition of HDACs, miRNAs, and the modification of the CpG methylation of cancer-related genes). In this review, we will discuss: the current advances in the study of Nrf2 signaling; Nrf2-deficient tumor mouse models; the epigenetic control of Nrf2 in tumorigenesis and chemoprevention; Nrf2-mediated cancer chemoprevention by naturally occurring dietary phytochemicals; and the mutation or hyper-expression of the Nrf2–Keap1 signaling pathway in advanced tumor cells. The future development of dietary phytochemicals for chemoprevention must integrate in vitro signaling mechanisms, relevant biomarkers of human diseases, and combinations of different phytochemicals and/or non-toxic therapeutic drugs, including

  16. 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.

  17. 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.

  18. Plumbagin induces cell death through a copper-redox cycle mechanism in human cancer cells.

    Science.gov (United States)

    Nazeem, S; Azmi, Asfar S; Hanif, Sarmad; Ahmad, Aamir; Mohammad, Ramzi M; Hadi, S M; Kumar, K Sateesh

    2009-09-01

    Plumbagin, a naphthoquinone derived from the medicinal plant Plumbago zeylanica has been shown to exert anticancer and anti-proliferative activities in cells in culture as well as animal tumor models. In our previous paper, we have reported the cytotoxic action of plumbagin in plasmid pBR322 DNA as well as human peripheral blood lymphocytes through a redox mechanism involving copper. Copper has been shown to be capable of mediating the action of several plant-derived compounds through production of reactive oxygen species (ROS). The objective of the present study was to determine whether plumbagin induces apoptosis in human cancer cells through the same mechanism which we proposed earlier. Using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay, 3-(4,5-B-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay for cell growth inhibition, histone/DNA ELISA, homogeneous caspase-3/7 assay for apoptosis as well as alkaline comet assay for DNA single-strand breaks detection in this report, we confirm that plumbagin causes effective cell growth inhibition, induces apoptosis and generates single-strand breaks in cancer cells. Incubation of cancer cells with scavengers of ROS and neocuproine inhibited the cytotoxic action of plumbagin proving that generation of ROS and Cu(I) are the critical mediators in plumbagin-induced cell growth inhibition. This study is the first to investigate the copper-mediated anticancer mechanism of plumbagin in human cancer cells and these properties of plumbagin could be further explored for the development of anticancer agents with higher therapeutic indices, especially for skin cancer.

  19. Does Desire for Hastened Death Change in Terminally Ill Cancer Patients?

    OpenAIRE

    Rosenfeld, Barry; Pessin, Hayley; Marziliano, Allison; Jacobson, Coleen; Sorger, Brooke; Abbey, Jennifer; Olden, Megan; Brescia, Robert; Breitbart, William

    2014-01-01

    Understanding why some terminally ill patients may seek a hastened death (a construct referred to as “desire for hastened death” or DHD) is critical to understanding how to optimize quality of life during an individual’s final weeks, months or even years of life. Although a number of predictor variables have emerged in past DHD research, there is a dearth of longitudinal research on how DHD changes over time and what factors might explain such changes. This study examined DHD over time in a s...

  20. Second Cancers and Richter’s Transformation are the Leading Causes of Death in Patients with Trisomy 12 Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Strati, Paolo; Abruzzo, Lynne V.; Wierda, William G.; O’Brien, Susan; Ferrajoli, Alessandra; Keating, Michael J.

    2016-01-01

    Trisomy 12 (+12) is detected by fluorescence in situ hybridization (FISH) analysis in up to 20% of patients with chronic lymphocytic leukemia (CLL). Patients with +12 are known to have unique features and to carry an intermediate prognosis. In order to better define this large group, we reviewed the characteristics of 250 untreated patients with +12. When compared to 516 untreated patients negative for +12 by FISH, patients with +12 showed a higher incidence of thrombocytopenia, Richter Transformation (RT) and second malignant neoplasms (SMN), in addition to the expected increased rate of CD38 positivity and atypical immunophenotype. At a median follow-up of 51 months, 57% of patients needed first-line treatment; median time-to-first-treatment was 38 months and on multivariate analysis (MVA) it was shorter in patients with advanced Rai stage, palpable splenomegaly, and deletion 14q by conventional cytogenetic analysis. The overall response rate with first-line treatment was 94%. The median failure-free survival has not been reached, but on MVA it was shorter in patients who achieved a response other than complete remission or with FISH negativity for deletion 13q. The median overall survival for the entire group has not been reached, but on MVA it was shorter in patients with an absolute lymphocyte count >30×109/L or who developed SMN. Eighteen deaths have been observed so far, and RT and SMN were the leading causes of death (3 and 6, respectively). In conclusion, patients with +12 CLL show characteristic clinical and biological features, and may benefit from increased surveillance for second cancers. PMID:25800543

  1. 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death.

    Science.gov (United States)

    Ray, Anasuya; Vasudevan, Smreti; Sengupta, Suparna

    2015-01-01

    Cancer stem cells (CSCs) pose a serious obstacle to cancer therapy as they can be responsible for poor prognosis and tumour relapse. In this study, we have investigated inhibitory activity of the ginger-derived compound 6-shogaol against breast cancer cells both in monolayer and in cancer-stem cell-like spheroid culture. The spheroids were generated from adherent breast cancer cells. 6-shogaol was effective in killing both breast cancer monolayer cells and spheroids at doses that were not toxic to noncancerous cells. The percentages of CD44+CD24-/low cells and the secondary sphere content were reduced drastically upon treatment with 6-shogaol confirming its action on CSCs. Treatment with 6-shogaol caused cytoplasmic vacuole formation and cleavage of microtubule associated protein Light Chain3 (LC3) in both monolayer and spheroid culture indicating that it induced autophagy. Kinetic analysis of the LC3 expression and a combination treatment with chloroquine revealed that the autophagic flux instigated cell death in 6-shogaol treated breast cancer cells in contrast to the autophagy inhibitor chloroquine. Furthermore, 6-shogaol-induced cell death got suppressed in the presence of chloroquine and a very low level of apoptosis was exhibited even after prolonged treatment of the compound, suggesting that autophagy is the major mode of cell death induced by 6-shogaol in breast cancer cells. 6-shogaol reduced the expression levels of Cleaved Notch1 and its target proteins Hes1 and Cyclin D1 in spheroids, and the reduction was further pronounced in the presence of a γ-secretase inhibitor. Secondary sphere formation in the presence of the inhibitor was also further reduced by 6-shogaol. Together, these results indicate that the inhibitory action of 6-shogaol on spheroid growth and sustainability is conferred through γ-secretase mediated down-regulation of Notch signaling. The efficacy of 6-shogaol in monolayer and cancer stem cell-like spheroids raise hope for its

  2. Glucose restriction induces cell death in parental but not in homeodomain-interacting protein kinase 2-depleted RKO colon cancer cells: molecular mechanisms and implications for tumor therapy.

    Science.gov (United States)

    Garufi, A; Ricci, A; Trisciuoglio, D; Iorio, E; Carpinelli, G; Pistritto, G; Cirone, M; D'Orazi, G

    2013-05-23

    Tumor cell tolerance to nutrient deprivation can be an important factor for tumor progression, and may depend on deregulation of both oncogenes and oncosuppressor proteins. Homeodomain-interacting protein kinase 2 (HIPK2) is an oncosuppressor that, following its activation by several cellular stress, induces cancer cell death via p53-dependent or -independent pathways. Here, we used genetically matched human RKO colon cancer cells harboring wt-HIPK2 (HIPK2(+/+)) or stable HIPK2 siRNA interference (siHIPK2) to investigate in vitro whether HIPK2 influenced cell death in glucose restriction. We found that glucose starvation induced cell death, mainly due to c-Jun NH2-terminal kinase activation, in HIPK2(+/+)cells compared with siHIPK2 cells that did not die. (1)H-nuclear magnetic resonance quantitative metabolic analyses showed a marked glycolytic activation in siHIPK2 cells. However, treatment with glycolysis inhibitor 2-deoxy-D-glucose induced cell death only in HIPK2(+/+) cells but not in siHIPK2 cells. Similarly, siGlut-1 interference did not re-establish siHIPK2 cell death under glucose restriction, whereas marked cell death was reached only after zinc supplementation, a condition known to reactivate misfolded p53 and inhibit the pseudohypoxic phenotype in this setting. Further siHIPK2 cell death was reached with zinc in combination with autophagy inhibitor. We propose that the metabolic changes acquired by cells after HIPK2 silencing may contribute to induce resistance to cell death in glucose restriction condition, and therefore be directly relevant for tumor progression. Moreover, elimination of such a tolerance might serve as a new strategy for cancer therapy.

  3. Retrospective observation on contribution and limitations of screening for breast cancer with mammography in Korea: detection rate of breast cancer and incidence rate of interval cancer of the breast

    OpenAIRE

    2016-01-01

    Background The purpose of this study was to determine the benefits and limitations of screening for breast cancer using mammography. Methods Descriptive design with follow-up was used in the study. Data from breast cancer screening and health insurance claim data were used. The study population consisted of all participants in breast cancer screening from 2009 to 2014. Crude detection rate, positive predictive value and sensitivity and specificity of breast cancer screening and, incidence rat...

  4. Cancer incidence rate ratios of Turkish immigrants in Hamburg, Germany: A registry based study.

    Science.gov (United States)

    Spallek, Jacob; Arnold, Melina; Hentschel, Stefan; Razum, Oliver

    2009-12-01

    The aim of this study was to estimate cancer incidence rate ratios for Turkish migrants in Hamburg, Germany. We used a name-based approach and identified 1346 cases with Turkish names (as a proxy of Turkish origin) among 140,249 cases of cancer registered in the cancer registry Hamburg during 1990-2005. To estimate the size of the denominator population, we applied the name-based approach to the population of Hamburg as well. The cancer incidence of specific cancer sites was compared between Turkish and non-Turkish cases using incidence rate ratios (IRR), stratified by gender and birth cohort. Our main findings are that cancer of the respiratory organs is diagnosed less frequent among Turkish men in older birth cohorts but with higher frequency in the younger birth cohorts. Malignant neoplasms of lymphoid, haematopoietic and related tissues are slightly higher in most male Turkish men birth cohorts, and even considerably higher for the birth cohort 1961 to <1971 (IRR=1.8). Among women, incidence rates for Turkish women are lower than for non-Turkish women for cancer of the respiratory system, skin cancer and cancer of genital organs. Also, breast cancer incidence rates of Turkish women are lower than for non-Turkish women, especially in older birth cohorts. Incidence rate ratios of neoplasms of lymphoid, haematopoietic and related tissues are low in the 1931 to <1941 cohort (IRR=0.71) but increase in younger birth cohorts. In conclusion, we found differences in cancer risks between cases with and without Turkish names for specific cancer sites. These results are consistent with the findings of studies from other countries.

  5. 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.

  6. 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

  7. 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

  8. TFF3 and survivin expressions associate with a lower survival rate in gastric cancer.

    Science.gov (United States)

    Meng, Jia-Rong; Tang, Hui-Zhong; Zhou, Kai-Zong; Shen, Wu-Hong; Guo, He-Yi

    2013-11-01

    Trefoil factor 3 (TFF3) and survivin with functions of inhibiting apoptosis are involved in the gastric cancer by overexpression. The purpose of this study is to examine the expression of TFF3 and survivin in patients' tissue samples with gastric cancer and analyze the relationship between the protein expression and the different clinical records. By studying the expressions of TFF3 and survivin in gastric cancer through immunohistochemical staining and examining the survival rate via Kaplan-Meier analysis for gastric cancer patients, we found that the TFF3 and survivin positive expressions have a significant relationship with the lower survival rate comparing to that of negative expressions in the analyzed patients (P TFF3 and survivin expressions have the lowest survival rate. TFF3 or survivin positive expression correlates with the lymph node metastasis, metastasis, and TNM stages of gastric cancer. Survival analysis indicates that survival rate has a close relationship with the age, tumor histology, tumor differentiation, degree of infiltration, lymph node metastasis, distant metastasis, and TNM stages (P TFF3 and survivin expressions play a vital role in gastric cancer development, and these two proteins are important markers for prognosis in gastric cancer. Patients with gastric cancer can increase the survival rate through an earlier diagnosis and appropriate treatment.

  9. 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.

  10. Noxa and cancer therapy: Tuning up the mitochondrial death machinery in response to chemotherapy.

    Science.gov (United States)

    Albert, Marie-Christine; Brinkmann, Kerstin; Kashkar, Hamid

    2014-01-01

    Biochemical analyses have characterized the BH3-only protein family member Noxa as a "sensitizer" with weak pro-apoptotic activity. Investigations into cancer cell responses to chemotherapeutic agents have identified Noxa as a pivotal factor mediating the cytotoxic effect of a plethora of anticancer treatments independent of its own pro-apoptotic activity. Accumulating evidence now suggests that tumor cells exert a number of strategies to counteract Noxa function by exploiting diverse cellular regulatory circuits that normally govern Noxa expression during cellular stress responses. Here, we summarize data concerning the role of Noxa in cancer chemosensitivity and highlight the potential of this enigmatic BH3-only protein family member in current and novel anticancer therapies.

  11. Theracurmin® efficiently inhibits the growth of human prostate and bladder cancer cells via induction of apoptotic cell death and cell cycle arrest.

    Science.gov (United States)

    Kang, Minyong; Ho, Jin-Nyoung; Kook, Ha Rim; Lee, Sangchul; Oh, Jong Jin; Hong, Sung Kyu; Lee, Sang Eun; Byun, Seok-Soo

    2016-03-01

    In the present study, we aimed to investigate the anticancer properties of Theracurmin®, a novel form of the yellow curry pigment curcumin, as well as explore the molecular mechanisms of the potential anticancer effects of Theracurmin® on human prostate cancer and bladder cancer cells in vitro. The proliferation of cancer cells was examined by using the Cell Counting Kit-8. The clonogenic growth potential was determined by clonogenic assay. Cell cycle distribution was evaluated by flow cytometry using propidium iodide staining. Western blot analysis was applied to explore the expression patterns of molecules associated with apoptotic cell death and cell cycle checkpoint. We noted that Theracurmin® and curcumin exhibited similar anticancer effects in both androgen-dependent and -independent human prostate cancer cells in a dose- and time-dependent manner. These agents reduced cell viability and clonogenic growth potential by inducing apoptosis and cell cycle disturbance in human prostate cancer cells. Theracurmin® and curcumin also exerted marked anticancer effects on human bladder cancer cells, even in cisplatin-resistant T24R2 cells, in a dose- and time-dependent manner. Moreover, Theracurmin® and curcumin treatment decreased cell viability and clonogenicity via induction of apoptotic cell death and cell cycle dysregulation in human bladder cancer cells. In conclusion, our study suggests that Theracurmin® has potential as an anticancer agent in complementary and alternative medicine for these urological cancers.

  12. Autophagy inhibits cell death induced by the anti-cancer drug morusin

    Science.gov (United States)

    Cho, Sang Woo; Na, Wooju; Choi, Minji; Kang, Shin Jung; Lee, Seok-Geun; Choi, Cheol Yong

    2017-01-01

    Autophagy is a cellular process by which damaged organelles and dysfunctional proteins are degraded. Morusin is an anti-cancer drug isolated from the root bark of Morus alba. Morusin induces apoptosis in human prostate cancer cells by reducing STAT3 activity. In this study, we examined whether morusin induces autophagy and also examined the effects of autophagy on the morusin-induced apoptosis. Morusin induces LC3-II accumulation and ULK1 activation in HeLa cells. In addition, we found that induction of ULK1 Ser317 phosphorylation and reduction of ULK1 Ser757 phosphorylation occurred simultaneously during morusin-induced autophagy. Consistently, morusin induces autophagy by activation of AMPK and inhibition of mTOR activity. Next, we investigated the role of autophagy in morusin-induced apoptosis. Inhibition of autophagy by treating cells with the 3-methyladenine (3-MA) autophagic inhibitor induces high levels of morusin-mediated apoptosis, while treatment of cells with morusin alone induces moderate levels of apoptosis. Cell survival was greatly reduced when cells were treated with morusin and 3-MA. Taken together, morusin induces autophagy, which is an impediment for morusin-induced apoptosis, suggesting combined treatment of morusin with an autophagic inhibitor would increase the efficacy of morusin as an anti-cancer drug.

  13. ATM Inhibition Potentiates Death of Androgen Receptor-inactivated Prostate Cancer Cells with Telomere Dysfunction.

    Science.gov (United States)

    Reddy, Vidyavathi; Wu, Min; Ciavattone, Nicholas; McKenty, Nathan; Menon, Mani; Barrack, Evelyn R; Reddy, G Prem-Veer; Kim, Sahn-Ho

    2015-10-16

    Androgen receptor (AR) plays a role in maintaining telomere stability in prostate cancer cells, as AR inactivation induces telomere dysfunction within 3 h. Since telomere dysfunction in other systems is known to activate ATM (ataxia telangiectasia mutated)-mediated DNA damage response (DDR) signaling pathways, we investigated the role of ATM-mediated DDR signaling in AR-inactivated prostate cancer cells. Indeed, the induction of telomere dysfunction in cells treated with AR-antagonists (Casodex or MDV3100) or AR-siRNA was associated with a dramatic increase in phosphorylation (activation) of ATM and its downstream effector Chk2 and the presenceof phosphorylated ATM at telomeres, indicating activation of DDR signaling at telomeres. Moreover, Casodex washout led to the reversal of telomere dysfunction, indicating repair of damaged telomeres. ATM inhibitor blocked ATM phosphorylation, induced PARP cleavage, abrogated cell cycle checkpoint activation and attenuated the formation of γH2AX foci at telomeres in AR-inactivated cells, suggesting that ATM inhibitor induces apoptosis in AR-inactivated cells by blocking the repair of damaged DNA at telomeres. Finally, colony formation assay revealed a dramatic decrease in the survival of cells co-treated with Casodex and ATM inhibitor as compared with those treated with either Casodex or ATM inhibitor alone. These observations indicate that inhibitors of DDR signaling pathways may offer a unique opportunity to enhance the potency of AR-targeted therapies for the treatment of androgen-sensitive as well as castration-resistant prostate cancer.

  14. MiR-129-5p is required for histone deacetylase inhibitor-induced cell death in thyroid cancer cells.

    Science.gov (United States)

    Brest, Patrick; Lassalle, Sandra; Hofman, Veronique; Bordone, Olivier; Gavric Tanga, Virginie; Bonnetaud, Christelle; Moreilhon, Chimene; Rios, Geraldine; Santini, José; Barbry, Pascal; Svanborg, Catharina; Mograbi, Baharia; Mari, Bernard; Hofman, Paul

    2011-12-01

    The molecular mechanism responsible for the antitumor activity of histone deacetylase inhibitors (HDACi) remains elusive. As HDACi have been described to alter miRNA expression, the aim of this study was to characterize HDACi-induced miRNAs and to determine their functional importance in the induction of cell death alone or in combination with other cancer drugs. Two HDACi, trichostatin A and vorinostat, induced miR-129-5p overexpression, histone acetylation and cell death in BCPAP, TPC-1, 8505C, and CAL62 cell lines and in primary cultures of papillary thyroid cancer (PTC) cells. In addition, miR-129-5p alone was sufficient to induce cell death and knockdown experiments showed that expression of this miRNA was required for HDACi-induced cell death. Moreover, miR-129-5p accentuated the anti-proliferative effects of other cancer drugs such as etoposide or human α-lactalbumin made lethal for tumor cells (HAMLET). Taken together, our data show that miR-129-5p is involved in the antitumor activity of HDACi and highlight a miRNA-driven cell death mechanism.

  15. Development and validation of the Cancer Dyspnoea Scale: a multidimensional, brief, self-rating scale

    OpenAIRE

    K. Tanaka; Akechi, T.; T. Okuyama; Nishiwaki,Y; Uchitomi, Y

    2000-01-01

    Dyspnoea is one of the most frequent and refractory symptoms in cancer patients. Lack of an appropriate assessment tool for dyspnoea seems to disturb establishment of management strategy. The purpose of this study was to develop and validate a brief self-rating scale to assess the multidimensional nature of dyspnoea in cancer patients. We developed a 12-item scale, the Cancer Dyspnoea Scale (CDS), composed of three factors (sense of effort/sense of anxiety/sense of discomfort), by using facto...

  16. Estimation of an optimal chemotherapy utilisation rate for cancer: setting an evidence-based benchmark for quality cancer care.

    Science.gov (United States)

    Jacob, S A; Ng, W L; Do, V

    2015-02-01

    There is wide variation in the proportion of newly diagnosed cancer patients who receive chemotherapy, indicating the need for a benchmark rate of chemotherapy utilisation. This study describes an evidence-based model that estimates the proportion of new cancer patients in whom chemotherapy is indicated at least once (defined as the optimal chemotherapy utilisation rate). The optimal chemotherapy utilisation rate can act as a benchmark for measuring and improving the quality of care. Models of optimal chemotherapy utilisation were constructed for each cancer site based on indications for chemotherapy identified from evidence-based treatment guidelines. Data on the proportion of patient- and tumour-related attributes for which chemotherapy was indicated were obtained, using population-based data where possible. Treatment indications and epidemiological data were merged to calculate the optimal chemotherapy utilisation rate. Monte Carlo simulations and sensitivity analyses were used to assess the effect of controversial chemotherapy indications and variations in epidemiological data on our model. Chemotherapy is indicated at least once in 49.1% (95% confidence interval 48.8-49.6%) of all new cancer patients in Australia. The optimal chemotherapy utilisation rates for individual tumour sites ranged from a low of 13% in thyroid cancers to a high of 94% in myeloma. The optimal chemotherapy utilisation rate can serve as a benchmark for planning chemotherapy services on a population basis. The model can be used to evaluate service delivery by comparing the benchmark rate with patterns of care data. The overall estimate for other countries can be obtained by substituting the relevant distribution of cancer types. It can also be used to predict future chemotherapy workload and can be easily modified to take into account future changes in cancer incidence, presentation stage or chemotherapy indications.

  17. Synthesis of microtubule-interfering halogenated noscapine analogs that perturb mitosis in cancer cells followed by cell death.

    Science.gov (United States)

    Aneja, Ritu; Vangapandu, Surya N; Lopus, Manu; Viswesarappa, Vijaya G; Dhiman, Neerupma; Verma, Akhilesh; Chandra, Ramesh; Panda, Dulal; Joshi, Harish C

    2006-08-14

    We have previously identified the naturally occurring non-toxic antitussive phthalideisoquinoline alkaloid, noscapine as a tubulin-binding agent that arrests mitosis and induces apoptosis. Here we present high-yield efficient synthetic methods and an evaluation of anticancer activity of halogenated noscapine analogs. Our results show that all analogs display higher tubulin-binding activity than noscapine and inhibit proliferation of human cancer cells (MCF-7, MDA-MB-231 and CEM). Surprisingly, the bromo-analog is approximately 40-fold more potent than noscapine in inhibiting cellular proliferation of MCF-7 cells. The ability of these analogs to inhibit cellular proliferation is mediated by cell cycle arrest at the G2/M phase, in that all analogs except 9-iodonoscapine, caused selective mitotic arrest with a higher efficiency than noscapine followed by apoptotic cell death as shown by immunofluorescence and quantitative FACS analyses. Furthermore, our results reveal the appearance of numerous fragmented nuclei as evidenced by DAPI staining. Thus, our data indicate a great potential of these compounds for studying microtubule-mediated processes and as chemotherapeutic agents for the management of human cancers.

  18. 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

    2016-05-11

    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.

  19. Cathepsin B mediates caspase-independent cell death induced by microtubule stabilizing agents in non-small cell lung cancer cells.

    NARCIS (Netherlands)

    Broker, L.E.; Huisman, C.; Span, SW; Rodriguez, J.A.; Kruyt, F.A.E.; Giaccone, G.

    2004-01-01

    We have previously reported that the microtubule stabilizing agents (MSAs) paclitaxel, epothilone B and discodermolide induce caspase-independent cell death in non-small cell lung cancer (NSCLC) cells. Here we present two lines of evidence indicating a central role for the lysosomal protease catheps

  20. Using continuous sedation until death for cancer patients: A qualitative interview study of physicians' and nurses' practice in three European countries

    NARCIS (Netherlands)

    J. Seymour (Jane); J.A.C. Rietjens (Judith); S.M. Bruinsma (Sophie); L. Deliens (Luc); S. Sterckx (Sigrid); F. Mortier (Freddy); J. Brown (Jayne); N. Mathers (Nigel); A. van der Heide (Agnes)

    2015-01-01

    textabstractBackground: Extensive debate surrounds the practice of continuous sedation until death to control refractory symptoms in terminal cancer care. We examined reported practice of United Kingdom, Belgian and Dutch physicians and nurses. Methods: Qualitative case studies using interviews. Set

  1. Impact of primary local treatment on the development of distant metastases or death through locoregional recurrence in young breast cancer patients

    NARCIS (Netherlands)

    Bantema-Joppe, E. J.; van den Heuvel, E. R.; de Munck, L.; de Bock, G. H.; Smit, W. G. J. M.; Timmer, P. R.; Dolsma, W. V.; Jansen, L.; Siesling, S.; Langendijk, J. A.; Maduro, J. H.; Schroder, Carolien; Schroder, Carolien

    2013-01-01

    In this study, we tested the hypothesis whether breast conserving therapy (BCT) compared with mastectomy is associated with a negative outcome in terms of distant metastases or death (DMD) and investigated the relation between locoregional recurrence (LRR) and DMD in young breast cancer (BC) patient

  2. Oral cancer incidence and survival rates in the Republic of Ireland, 1994-2009.

    LENUS (Irish Health Repository)

    Ali, Hala

    2016-12-20

    Oral cancer is a significant public health problem world-wide and exerts high economic, social, psychological, and physical burdens on patients, their families, and on their primary care providers. We set out to describe the changing trends in incidence and survival rates of oral cancer in Ireland between 1994 and 2009.

  3. 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 ...

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

    OpenAIRE

    2012-01-01

    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...

  5. 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.

  6. Lymph node density predicts recurrence and death after inguinal lymph node dissection for penile cancer

    Science.gov (United States)

    Schwen, Zeyad R.; Ko, Joan S.; Meyer, Alexa; Netto, George J.; Burnett, Arthur L.; Bivalacqua, Trinity J.

    2017-01-01

    Purpose To determine the impact of lymph node density (LND) on survival after inguinal lymph node dissection (ILND) for penile cancer. Materials and Methods Our institutional penile cancer database was queried for patients who underwent ILND. Clinicopathologic characteristics including LND and total number of positive lymph nodes (LNs) were analyzed to determine impact on recurrence-free survival (RFS) and overall survival (OS). LND, or the percent of positive LN out of total LN, was calculated as a categorical variable at varying thresholds. Results Twenty-eight patients with complete follow-up were identified. Indications for ILND were stage >T2 in 20 patients (71.4%), palpable adenopathy in 7 (25%), high grade T1 in 1 (3.6%). Median node yield was 17.5 (interquartile range, 12−22), and positive LNs were found in 14 patients (50%). RFS and OS were significantly lower for patients with >15% LN density (median RFS: 62 months vs. 6.3 months, p=0.0120; median OS: 73.6 months vs. 6.3 months, p15% was independently associated with worse RFS (hazard ratio [HR], 3.6; p=0.04) and OS (HR, 73.6; p=0.002). The c-index for LND was higher than total positive LNs for RFS (0.64 vs. 0.54) and OS (0.79 vs. 0.61). Conclusions In this small, retrospective penile cancer cohort, the presence of nodal involvement >15% was associated with decreased RFS and OS, and outperformed total number of positive LN as a prognostic indicator.

  7. 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.

  8. Calcium homeostasis and mitochondrial function during death of prostate cancer cells exposed to statins

    OpenAIRE

    Kivia Aparecida Pontes de Oliveira

    2008-01-01

    Resumo: As estatinas são inibidores da 3-hidroxi-3-metilglutaril CoA (HMG-CoA) redutase usados no tratamento de hipercolesterolemia. Estudos in vitro e in vivo têm demonstrado que as estatinas podem ter efeitos anti-cancerígenos. No presente estudo analisamos os mecanismos de toxicidade de sinvastatina e de lovastatina nas linhagens de câncer de próstata LNCaP e PC-3. Curvas dose-resposta do efeito das estatinas (0,1-100 µM) sobre as células LNCaP e PC-3 mostraram efeitos similares e maior se...

  9. Cancer detection rates of different prostate biopsy regimens in patients with renal failure.

    Science.gov (United States)

    Hoşcan, Mustafa Burak; Özorak, Alper; Oksay, Taylan; Perk, Hakkı; Armağan, Abdullah; Soyupek, Sedat; Serel, Tekin Ahmet; Koşar, Alim

    2014-07-01

    We aimed to evaluate the cancer detection rates of 6-, 10-, 12-core biopsy regimens and the optimal biopsy protocol for prostate cancer diagnosis in patients with renal failure. A total of 122 consecutive patients with renal failure underwent biopsy with age-specific prostate-specific antigen (PSA) levels up to 20 ng/mL. The 12-core biopsy technique (sextant biopsy + lateral base, lateral mid-zone, lateral apex, bilaterally) performed to all patients. Pathology results were examined separately for each sextant, 10-core that exclude parasagittal mid-zones from 12-cores (10a), 10-core that exclude apex zones from 12-cores (10b) and 12-core biopsy regimens. Of 122 patients, 37 (30.3%) were positive for prostate cancer. The cancer detection rates for sextant, 10a, 10b and 12 cores were 17.2%, 29%, 23.7% and 30.7%, respectively. Biopsy techniques of 10a, 10b and 12 cores increased the cancer detection rates by 40%, 27.5% and 43.2% among the sextant technique, respectively. Biopsy techniques of 10a and 12 cores increased the cancer detection rates by 17.1% and 21.6% among 10b biopsy technique, respectively. There were no statistical differences between 12 core and 10a core about cancer detection rate. Adding lateral cores to sextant biopsy improves the cancer detection rates. In our study, 12-core biopsy technique increases the cancer detection rate by 5.4% among 10a core but that was not statistically different. On the other hand, 12-core biopsy technique includes all biopsy regimens. We therefore suggest 12-core biopsy or minimum 10-core strategy incorporating six peripheral biopsies with elevated age- specific PSA levels up to 20 ng/mL in patients with renal failure.

  10. The attitudes of brain cancer patients and their caregivers towards death and dying: a qualitative study

    Directory of Open Access Journals (Sweden)

    Kimmelman Jonathan

    2007-11-01

    Full Text Available Abstract Background Much money and energy has been spent on the study of the molecular biology of malignant brain tumours. However, little attention has been paid to the wishes of patients afflicted with these incurable tumours, and how this might influence treatment considerations. Methods We interviewed 29 individuals – 7 patients dying of a malignant brain tumor and 22 loved ones. One-on-one interviews were conducted according to a pre-designed interview guide. A combination of open-ended questions, as well as clinical scenarios was presented to participants in order to understand what is meaningful and valuable to them when determining treatment options and management approaches. The results were analyzed, coded, and interpreted using qualitative analytic techniques in order to arrive at several common overarching themes. Results Seven major themes were identified. In general, respondents were united in viewing brain cancer as unique amongst malignancies, due in large part to the premium placed on mental competence and cognitive functioning. Importantly, participants found their experiences, however difficult, led to the discovery of inner strength and resilience. Responses were usually framed within an interpersonal context, and participants were generally grateful for the opportunity to speak about their experiences. Attitudes towards religion, spirituality, and euthanasia were also probed. Conclusion Several important themes underlie the experiences of brain cancer patients and their caregivers. It is important to consider these when managing these patients and to respect not only their autonomy but also the complex interpersonal toll that a malignant diagnosis can have.

  11. 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.

  12. SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty acids.

    Directory of Open Access Journals (Sweden)

    Paul Mason

    Full Text Available Increased metabolism is a requirement for tumor cell proliferation. To understand the dependence of tumor cells on fatty acid metabolism, we evaluated various nodes of the fatty acid synthesis pathway. Using RNAi we have demonstrated that depletion of fatty-acid synthesis pathway enzymes SCD1, FASN, or ACC1 in HCT116 colon cancer cells results in cytotoxicity that is reversible by addition of exogenous fatty acids. This conditional phenotype is most pronounced when SCD1 is depleted. We used this fatty-acid rescue strategy to characterize several small-molecule inhibitors of fatty acid synthesis, including identification of TOFA as a potent SCD1 inhibitor, representing a previously undescribed activity for this compound. Reference FASN and ACC inhibitors show cytotoxicity that is less pronounced than that of TOFA, and fatty-acid rescue profiles consistent with their proposed enzyme targets. Two reference SCD1 inhibitors show low-nanomolar cytotoxicity that is offset by at least two orders of magnitude by exogenous oleate. One of these inhibitors slows growth of HCT116 xenograft tumors. Our data outline an effective strategy for interrogation of on-mechanism potency and pathway-node-specificity of fatty acid synthesis inhibitors, establish an unambiguous link between fatty acid synthesis and cancer cell survival, and point toward SCD1 as a key target in this pathway.

  13. 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.

  14. 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.

  15. Impact on mortality and cancer incidence rates of using random invitation from population registers for recruitment to trials

    Directory of Open Access Journals (Sweden)

    Woolas Robert

    2011-03-01

    Full Text Available Abstract Background Participants in trials evaluating preventive interventions such as screening are on average healthier than the general population. To decrease this 'healthy volunteer effect' (HVE women were randomly invited from population registers to participate in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS and not allowed to self refer. This report assesses the extent of the HVE still prevalent in UKCTOCS and considers how certain shortfalls in mortality and incidence can be related to differences in socioeconomic status. Methods Between 2001 and 2005, 202 638 postmenopausal women joined the trial out of 1 243 312 women randomly invited from local health authority registers. The cohort was flagged for deaths and cancer registrations and mean follow up at censoring was 5.55 years for mortality, and 2.58 years for cancer incidence. Overall and cause-specific Standardised Mortality Ratios (SMRs and Standardised Incidence Ratios (SIRs were calculated based on national mortality (2005 and cancer incidence (2006 statistics. The Index of Multiple Deprivation (IMD 2007 was used to assess the link between socioeconomic status and mortality/cancer incidence, and differences between the invited and recruited populations. Results The SMR for all trial participants was 37%. By subgroup, the SMRs were higher for: younger age groups, extremes of BMI distribution and with each increasing year in trial. There was a clear trend between lower socioeconomic status and increased mortality but less pronounced with incidence. While the invited population had higher mean IMD scores (more deprived than the national average, those who joined the trial were less deprived. Conclusions Recruitment to screening trials through invitation from population registers does not prevent a pronounced HVE on mortality. The impact on cancer incidence is much smaller. Similar shortfalls can be expected in other screening RCTs and it maybe prudent

  16. Magnetic nanoparticles of Fe3O4 enhance docetaxel-induced prostate cancer cell death

    Directory of Open Access Journals (Sweden)

    Sato A

    2013-08-01

    Full Text Available Akiko Sato,1 Naoki Itcho,1 Hitoshi Ishiguro,2,3 Daiki Okamoto,1 Naohito Kobayashi,4 Kazuaki Kawai,5 Hiroshi Kasai,5 Daisuke Kurioka,1 Hiroji Uemura,2 Yoshinobu Kubota,2 Masatoshi Watanabe11Laboratory for Medical Engineering, Division of Materials Science and Chemical Engineering, Graduate School of Engineering, Yokohama National University, Yokohama, Japan; 2Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 3Photocatalyst Group, Kanagawa Academy of Science and Technology, Kawasaki, Japan; 4Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan; 5Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, JapanAbstract: Docetaxel (DTX is one of the most important anticancer drugs; however, the severity of its adverse effects detracts from its practical use in the clinic. Magnetic nanoparticles of Fe3O4 (MgNPs-Fe3O4 can enhance the delivery and efficacy of anticancer drugs. We investigated the effects of MgNPs-Fe3O4 or DTX alone, and in combination with prostate cancer cell growth in vitro, as well as with the mechanism underlying the cytotoxic effects. MgNPs-Fe3O4 caused dose-dependent increases in reactive oxygen species levels in DU145, PC-3, and LNCaP cells; 8-hydroxydeoxyguanosine levels were also elevated. MgNPs-Fe3O4 alone reduced the viability of LNCaP and PC-3 cells; however, MgNPs-Fe3O4 enhanced the cytotoxic effect of a low dose of DTX in all three cell lines. MgNPs-Fe3O4 also augmented the percentage of DU145 cells undergoing apoptosis following treatment with low dose DTX. Expression of nuclear transcription factor κB in DU145 was not affected by MgNPs-Fe3O4 or DTX alone; however, combined treatment suppressed nuclear transcription factor κB expression. These findings offer the possibility that MgNPs-Fe3O4–low dose DTX combination therapy may be

  17. Cancer Mortality Projections in Korea up to 2032.

    Science.gov (United States)

    Son, Mia; Yun, Jae-Won

    2016-06-01

    Predicting cancer mortality is important to estimate the needs of cancer-related services and to prevent cancer. Despite its significance, a long-term future projection of cancer mortality has not been conducted; therefore, our objective was to estimate future cancer mortality in Korea by cancer site through 2032. The specially designed Nordpred software was used to estimate cancer mortality. The cancer death data from 1983 to 2012 and the population projection data from 1983 to 2032 were obtained from the Korean National Statistics Office. Based on our analysis, age-standardized rates with the world standard population of all cancer deaths were estimated to decline from 2008-2012 to 2028-2032 (men: -39.8%, women: -33.1%). However, the crude rates are predicted to rise (men: 29.8%, women: 24.4%), and the overall number of the cancer deaths is also estimated to increase (men: 35.5%, women: 32.3%). Several cancer deaths are projected to increase (lung, liver and gallbladder, colon and rectum, pancreas and leukemia in both sexes; prostate cancer in men; and breast and ovarian cancer in women), whereas other cancer deaths are expected to decrease (stomach, esophagus and larynx in both sexes and cervical cancer in women). The largest contribution to increasing cancer deaths is due to the aging of the Korean population. In conclusion, a strategy for primary prevention, early detection, and early treatment to cope with the rapidly increasing death of cancer due to population aging is urgently required.

  18. 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

  19. 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

  20. Blacks' Death Rate Due to Circulatory Diseases Is Positively Related to Whites' Explicit Racial Bias: A Nationwide Investigation Using Project Implicit

    OpenAIRE

    2016-01-01

    Perceptions of racial bias have been linked to poorer circulatory health among Blacks compared with Whites. However, little is known about whether Whites' actual racial bias contributes to this racial disparity in health. We compiled racial-bias data from 1,391,632 Whites and examined whether racial bias in a given county predicted Black-White disparities in circulatory-disease risk (access to health care, diagnosis of a circulatory disease; Study 1) and circulatory-disease-related death rate...

  1. High dose rate versus low dose rate brachytherapy for oral cancer--a meta-analysis of clinical trials.

    Directory of Open Access Journals (Sweden)

    Zhenxing Liu

    Full Text Available OBJECTIVE: To compare the efficacy and safety of high dose rate (HDR and low dose rate (LDR brachytherapy in treating early-stage oral cancer. DATA SOURCES: A systematic search of MEDLINE, EMBASE and Cochrane Library databases, restricted to English language up to June 1, 2012, was performed to identify potentially relevant studies. STUDY SELECTION: Only randomized controlled trials (RCT and controlled trials that compared HDR to LDR brachytherapy in treatment of early-stage oral cancer (stages I, II and III were of interest. DATA EXTRACTION AND SYNTHESIS: Two investigators independently extracted data from retrieved studies and controversies were solved by discussion. Meta-analysis was performed using RevMan 5.1. One RCT and five controlled trials (607 patients: 447 for LDR and 160 for HDR met the inclusion criteria. The odds ratio showed no statistically significant difference between LDR group and HDR group in terms of local recurrence (OR = 1.12, CI 95% 0.62-2.01, overall mortality (OR = 1.01, CI 95% 0.61-1.66 and Grade 3/4 complications (OR = 0.86, CI 95% 0.52-1.42. CONCLUSIONS: This meta-analysis indicated that HDR brachytherapy was a comparable alternative to LDR brachytherapy in treatment of oral cancer. HDR brachytherapy might become a routine choice for early-stage oral cancer in the future.

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

    Directory of Open Access Journals (Sweden)

    Lionel Leclere

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

  3. Oxidative stress activates the TRPM2-Ca(2+)-CaMKII-ROS signaling loop to induce cell death in cancer cells.

    Science.gov (United States)

    Wang, Qian; Huang, Lihong; Yue, Jianbo

    2016-12-20

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

  4. 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...

  5. Prostate cancer incidence rates have started to decrease in central Italy.

    Science.gov (United States)

    Crocetti, Emanuele; Ciatto, Stefano; Buzzoni, Carlotta; Zappa, Marco

    2010-01-01

    The widespread use of prostate-specific antigen (PSA) testing has dramatically changed the epidemiology of prostate cancer. Growing incidence rates have been documented in almost all western countries following the increased usage of PSA screening. In the United States after a period of huge increase in incidence, rates have decreased to values lower than those of the pre-PSA era. Similar changes have been documented also in the area of the Tuscany Cancer Registry, central Italy, where prostate cancer incidence rates doubled from the early 1990s to 2003 and afterwards decreased. This is the first evidence, to our knowledge, of a decline in prostate cancer incidence in Italy following the screening-related increase.

  6. Breast cancer statistics, 2011.

    Science.gov (United States)

    DeSantis, Carol; Siegel, Rebecca; Bandi, Priti; Jemal, Ahmedin

    2011-01-01

    In this article, the American Cancer Society provides an overview of female breast cancer statistics in the United States, including trends in incidence, mortality, survival, and screening. Approximately 230,480 new cases of invasive breast cancer and 39,520 breast cancer deaths are expected to occur among US women in 2011. Breast cancer incidence rates were stable among all racial/ethnic groups from 2004 to 2008. Breast cancer death rates have been declining since the early 1990s for all women except American Indians/Alaska Natives, among whom rates have remained stable. Disparities in breast cancer death rates are evident by state, socioeconomic status, and race/ethnicity. While significant declines in mortality rates were observed for 36 states and the District of Columbia over the past 10 years, rates for 14 states remained level. Analyses by county-level poverty rates showed that the decrease in mortality rates began later and was slower among women residing in poor areas. As a result, the highest breast cancer death rates shifted from the affluent areas to the poor areas in the early 1990s. Screening rates continue to be lower in poor women compared with non-poor women, despite much progress in increasing mammography utilization. In 2008, 51.4% of poor women had undergone a screening mammogram in the past 2 years compared with 72.8% of non-poor women. Encouraging patients aged 40 years and older to have annual mammography and a clinical breast examination is the single most important step that clinicians can take to reduce suffering and death from breast cancer. Clinicians should also ensure that patients at high risk of breast cancer are identified and offered appropriate screening and follow-up. Continued progress in the control of breast cancer will require sustained and increased efforts to provide high-quality screening, diagnosis, and treatment to all segments of the population.

  7. Low heart rate variability and cancer-related fatigue in breast cancer survivors

    OpenAIRE

    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...

  8. A joint model for the dependence between clustered times to tumour progression and deaths: A meta-analysis of chemotherapy in head and neck cancer.

    Science.gov (United States)

    Rondeau, Virginie; Pignon, Jean-Pierre; Michiels, Stefan

    2015-12-01

    The observation of time to tumour progression (TTP) or progression-free survival (PFS) may be terminated by a terminal event. In this context, deaths may be due to tumour progression, and the time to the major failure event (death) may be correlated with the TTP. The usual assumption of independence between the TTP process and death, required by many commonly used statistical methods, can be violated. Furthermore, although the relationship between TTP and time to death is most relevant to the anti-cancer drug development or to evaluation of TTP as a surrogate endpoint, statistical models that try to describe the dependence structure between these two characteristics are not frequently used. We propose a joint frailty model for the analysis of two survival endpoints, TTP and time to death, or PFS and time to death, in the context of data clustering (e.g. at the centre or trial level). This approach allows us to simultaneously evaluate the prognostic effects of covariates on the two survival endpoints, while accounting both for the relationship between the outcomes and for data clustering. We show how a maximum penalized likelihood estimation can be applied to a nonparametric estimation of the continuous hazard functions in a general joint frailty model with right censoring and delayed entry. The model was motivated by a large meta-analysis of randomized trials for head and neck cancers (Meta-Analysis of Chemotherapy in Head and Neck Cancers), in which the efficacy of chemotherapy on TTP or PFS and overall survival was investigated, as adjunct to surgery or radiotherapy or both.

  9. Identification of an anabolic selective androgen receptor modulator that actively induces death of androgen-independent prostate cancer cells.

    Science.gov (United States)

    Schmidt, Azriel; Meissner, Robert S; Gentile, Michael A; Chisamore, Michael J; Opas, Evan E; Scafonas, Angela; Cusick, Tara E; Gambone, Carlo; Pennypacker, Brenda; Hodor, Paul; Perkins, James J; Bai, Chang; Ferraro, Damien; Bettoun, David J; Wilkinson, Hilary A; Alves, Stephen E; Flores, Osvaldo; Ray, William J

    2014-09-01

    Prostate cancer (PCa) initially responds to inhibition of androgen receptor (AR) signaling, but inevitably progresses to hormone ablation-resistant disease. Much effort is focused on optimizing this androgen deprivation strategy by improving hormone depletion and AR antagonism. However we found that bicalutamide, a clinically used antiandrogen, actually resembles a selective AR modulator (SARM), as it partially regulates 24% of endogenously 5α-dihydrotestosterone (DHT)-responsive genes in AR(+) MDA-MB-453 breast cancer cells. These data suggested that passive blocking of all AR functions is not required for PCa therapy. Hence, we adopted an active strategy that calls for the development of novel SARMs, which induce a unique gene expression profile that is intolerable to PCa cells. Therefore, we screened 3000 SARMs for the ability to arrest the androgen-independent growth of AR(+) 22Rv1 and LNCaP PCa cells but not AR(-) PC3 or DU145 cells. We identified only one such compound; the 4-aza-steroid, MK-4541, a potent and selective SARM. MK-4541 induces caspase-3 activity and cell death in both androgen-independent, AR(+) PCa cell lines but spares AR(-) cells or AR(+) non-PCa cells. This activity correlates with its promoter context- and cell-type dependent transcriptional effects. In rats, MK-4541 inhibits the trophic effects of DHT on the prostate, but not the levator ani muscle, and triggers an anabolic response in the periosteal compartment of bone. Therefore, MK-4541 has the potential to effectively manage prostatic hypertrophic diseases owing to its antitumor SARM-like mechanism, while simultaneously maintaining the anabolic benefits of natural androgens.

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

    Directory of Open Access Journals (Sweden)

    Makiko Naka Mieno

    2016-04-01

    Full Text Available 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, heart disease, and pneumonia reported on death certificates compared with a reference standard of pathologist assessment based on autopsy data and clinical records. Logistic regression analysis was performed to assess the effect of sex, age, comorbidity, and UCODs on misclassification. Results: The concordance rate was relatively high for cancer (81% but low for heart disease (55% and pneumonia (9%. The overall concordance rate was 48%. Sex and comorbidity did not affect UCOD misclassification rates, which tended to increase with patient age, although the association with age was also not significant. The strongest factor for misclassification was UCODs (P < 0.0001. Sensitivity and specificity for cancer were very high (80% and 96%, respectively, but sensitivity for heart disease and pneumonia was 60% and 46%, respectively. Specificity for each UCOD was more than 85%. Conclusions: Researchers should be aware of the accuracy of COD data from death certificates used as research resources, especially for cases of elderly patients with pneumonia.

  11. 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 ...

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

    Science.gov (United States)

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

    2016-04-01

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

  13. 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.

  14. 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.

  15. 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...

  16. 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.

  17. 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

  18. Urine estrogen profiles in European countries with high or low breast cancer rates

    NARCIS (Netherlands)

    Macmahon, B.; Andersen, A.P.; Brown, J.; Cole, P.; Dewaard, V.; Kauraniemi, T.; Ravhinar, B.; Stormby, N.; Trichopoulos, D.; Westlund, K.

    1980-01-01

    Urine estrogens of women in two age groups, 15 18 and 30-39, were measured in four northern European countries where breast cancer rates are high, two southern European countries where they are low, and in Finland, a northern country where incidence rates are comparable to those of the southern coun

  19. 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.

  20. 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.

  1. Molecular Mechanisms by Which a Fucus vesiculosus Extract Mediates Cell Cycle Inhibition and Cell Death in Pancreatic Cancer Cells.

    Science.gov (United States)

    Geisen, Ulf; Zenthoefer, Marion; Peipp, Matthias; Kerber, Jannik; Plenge, Johannes; Managò, Antonella; Fuhrmann, Markus; Geyer, Roland; Hennig, Steffen; Adam, Dieter; Piker, Levent; Rimbach, Gerald; Kalthoff, Holger

    2015-07-20

    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.

  2. 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

  3. Too Few Current, Former Smokers Screened for Lung Cancer

    Science.gov (United States)

    ... html Too Few Current, Former Smokers Screened for Lung Cancer Such testing could cut death rate by 20 ... the United States don't get screened for lung cancer even though they're at increased risk for ...

  4. The chalcone 2'-hydroxy-4',5'-dimethoxychalcone activates death receptor 5 pathway and leads to apoptosis in human nonsmall cell lung cancer cells.

    Science.gov (United States)

    Yang, Lina; Su, Ling; Cao, Congmei; Xu, Linyan; Zhong, Diansheng; Xu, Lijia; Liu, Xiangguo

    2013-06-01

    Natural chalcones have been proved to inhibit cancer cells with therapeutic potential, but the underlying molecular mechanism is still largely unexplored. Here, we identified a novel chalcone, 2'-hydroxy-4',5'-dimethoxychalcone (HDMC) and demonstrated that HDMC induced apoptosis in various nonsmall cell lung cancer cells. Further study showed that HDMC elevated cellular reactive oxygen species (ROS) levels, thus inducing expressions of ATF4 and C/EBP homologous protein (CHOP). Then, death receptor 5 (DR5) was upregulated through ATF4-CHOP axis and eventually resulted in apoptosis. We also found that downregulation of c-FLIPL contributed to HDMC-induced apoptosis. In conclusion, HDMC induces apoptosis in human nonsmall cell lung cancer cells via activation of DR5 signaling pathway, and ROS-mediated ATF4-CHOP axis is involved in the process. Our results further supported the potential for HDMC to be developed as a new antitumor agent for cancer therapy or chemoprevention.

  5. 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

    2008-01-01

    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......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...... and demonstrated that PDCD4 is a functionally important target for miR-21 in breast cancer cells....

  6. 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

    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 observed with fluorescence confocal microscopy of quinacrine-labelled U937 cells. RESULTS: Both H69 and SW780 cells showed dose-dependent (calcium concentration and electric field) decrease in intracellular ATP (p...-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....

  7. Detection of Cancer Cell Death Mediated by a Synthetic Granzyme B-like Peptide Fluorescent Conjugate and the same Peptide Binding in Bacteria.

    Science.gov (United States)

    Lo, Wai Chun Jennifer; Luther, Donald Gene

    2014-03-01

    Granzyme-mediated apoptosis, supported by pore-forming perforin, plays an important role in CD8+ T lymphocytes (CTL)-dependent cellular immunity protection against both cancer and viral infection. Quantitative and qualitative problems with CTL are potential contributing factors to disease progression. The feasibility of developing CTL-independent cellular immunity is desired but must first overcome the barrier of CTL-independent target cell recognition. Granzyme B with its strong pro-apoptotic activity in many different target cells is investigated for use in the CTL-independent cellular immunity approach, and granzyme B or its bioactive peptides without the enzymatic activity are more desirable for use. Native granzyme B with enzymatic activity is usually investigated in cancer cells for its mediation of apoptosis by detection of DNA fragmentation. Detection of cell death mediated by such peptides in cancer cells is needed to demonstrate the potential therapeutic purposes. We show with never-before-seen microscopic images using fluorescence microscopy that a synthetic granzyme B-like peptide fluorescent conjugate (GP1R) can: 1) mediate cell death of different cancer cells via membrane extrusion, 2) bind to constitutively expressed binding targets in different cancer cells and bacteria, and 3) promote bacterial phagocytosis. The putative binding targets may serve as a universal pathologic biomarker detectable by GP1R. Our data taken together demonstrate the potential applications of GP1R for use in CTL-independent target cell recognition and target cell death induction. It may lead to development of rapid targeted detection and new treatment of cancer, viral and bacterial infections. The new treatment may show mutual benefits for two or more diseases.

  8. Cancer mortality rates among first and second generation migrants in the Netherlands: convergence toward the rates of the native Dutch population.

    NARCIS (Netherlands)

    Stirbu, I.; Kunst, A.E.; Vlems, F.A.; Devillé, W.; Nijhuis, H.G.J.; Coebergh, J.W.

    2006-01-01

    This study investigates the difference in cancer mortality rates between migrant groups and the native Dutch population, and determines the extent of convergence of cancer mortality rates according to migrants' generation, age at migration and duration of residence. Data were obtained from the natio

  9. 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.

  10. Improvement in in vitro fertilization rate, decrease in reactive oxygen species and spermatozoa death incidence in rams by dietary fish oil.

    Science.gov (United States)

    Matini Behzad, A; Ebrahimi, B; Alizadeh, A R; Esmaeili, V; Dalman, A; Rashki, L; Shahverdi, A H

    2014-08-01

    Our aim was to evaluate the effects of fish oil feeding on sperm classical parameters, level of reactive oxygen spices (ROS), spermatozoa death incidence and in vitro fertilization (IVF) rate in rams. We randomly assigned nine rams, into two experimental groups (isoenergetic and isonitrogenous rations with constant level of vitamin E supplement): control (CTR; n = 5) and fish oil (FO; n = 4, 35 g/day/ram). Diets were fed for 70 days during the physiological breeding season. After a 21-day dietary adaptation period, semen was collected weekly from each ram by an artificial vagina. Sperm classical parameters were determined by the computer-assisted sperm analyzer system (CASA), and it was prepared for IVF process by swim-up technique. These evaluations were performed during the first and last weeks of sampling. Intracellular ROS level and spermatozoa death incidence were detected by flow cytometry on a weekly basis after adaptation. Data were analysed with SPSS 15. The volume, concentration (3.6 and 2.7 × 10(9) /ml) and sperm progressive motility (60 and 48%) were significantly improved in the FO group compared with the CTR (p < 0.05). A comparison of two-cell stage embryos following IVF in the two groups showed a significantly higher fertilization rate in the FO group (56%) compared with the CTR (49%). Superoxide anion (O2 (-) ) rate was significantly lower (p < 0.05) at the third week of sampling in the FO. Although the H2 O2 rate was numerically lower in the FO group compared with the CTR, this difference was not significant. In addition, apoptosis showed a significant difference in the third week of sampling (15 and 30% for FO and CTR, respectively; p < 0.05). Overall, adding fish oil to the ram diet not only improved sperm quality and IVF results, it also could reduce oxygen-free radicals and the incidence of spermatozoa death.

  11. 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.

  12. Application of Artificial Neural Network in Predicting the Survival Rate of Gastric Cancer Patients

    OpenAIRE

    Biglarian, A; E. Hajizadeh; Kazemnejad, A; Zali, MR

    2011-01-01

    "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...

  13. 6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death.

    Directory of Open Access Journals (Sweden)

    Anasuya Ray

    Full Text Available Cancer stem cells (CSCs pose a serious obstacle to cancer therapy as they can be responsible for poor prognosis and tumour relapse. In this study, we have investigated inhibitory activity of the ginger-derived compound 6-shogaol against breast cancer cells both in monolayer and in cancer-stem cell-like spheroid culture. The spheroids were generated from adherent breast cancer cells. 6-shogaol was effective in killing both breast cancer monolayer cells and spheroids at doses that were not toxic to noncancerous cells. The percentages of CD44+CD24-/low cells and the secondary sphere content were reduced drastically upon treatment with 6-shogaol confirming its action on CSCs. Treatment with 6-shogaol caused cytoplasmic vacuole formation and cleavage of microtubule associated protein Light Chain3 (LC3 in both monolayer and spheroid culture indicating that it induced autophagy. Kinetic analysis of the LC3 expression and a combination treatment with chloroquine revealed that the autophagic flux instigated cell death in 6-shogaol treated breast cancer cells in contrast to the autophagy inhibitor chloroquine. Furthermore, 6-shogaol-induced cell death got suppressed in the presence of chloroquine and a very low level of apoptosis was exhibited even after prolonged treatment of the compound, suggesting that autophagy is the major mode of cell death induced by 6-shogaol in breast cancer cells. 6-shogaol reduced the expression levels of Cleaved Notch1 and its target proteins Hes1 and Cyclin D1 in spheroids, and the reduction was further pronounced in the presence of a γ-secretase inhibitor. Secondary sphere formation in the presence of the inhibitor was also further reduced by 6-shogaol. Together, these results indicate that the inhibitory action of 6-shogaol on spheroid growth and sustainability is conferred through γ-secretase mediated down-regulation of Notch signaling. The efficacy of 6-shogaol in monolayer and cancer stem cell-like spheroids raise

  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. Feasibility of constant dose rate VMAT in the treatment of nasopharyngeal cancer patients

    OpenAIRE

    Yu, Wenliang; Shang, Haijiao; Xie, Congying; Han, CE; Yi, Jinling; Zhou, Yongqiang; Jin, Xiance

    2014-01-01

    Purpose To investigate the feasibility of constant dose rate volumetric modulated arc therapy (CDR-VMAT) in the treatment of nasopharyngeal cancer (NPC) patients and to introduce rotational arc radiotherapy for linacs incapable of dose rate variation. Materials and methods Twelve NPC patients with various stages treated previously using variable dose rate (VDR) VMAT were enrolled in this study. CDR-VMAT, VDR-VMAT and mutlicriteria optimization (MCO) VMAT plans were generated for each patient ...

  16. High Mortality Rate of Stomach Cancer Caused Not by High Incidence but Delays in Diagnosis in Aomori Prefecture, Japan

    Science.gov (United States)

    Matsuzaka, Masashi; Tanaka, Rina; Sasaki, Yoshihiro

    2016-10-01

    Background: There are substantial differences in the mortality rates of stomach cancer among the 47 prefectures in Japan, and Aomori prefecture is one of the most severely impacted. The aims of this study were to determine the incidence and mortality rates of stomach cancer in Aomori prefecture in comparison with Japan as a whole and cast light on reasons underlying variation. Methods: Data on stomach cancer cases were extracted from the Aomori Cancer Registry Database. Incidence rates for specific stages at the time of diagnosis were cited from Monitoring of Cancer Incidence in Japan, and mortality rates for stomach cancer in Aomori prefecture and the whole of Japan were obtained from Vital Statistics. Age-standardised incidence and mortality rates were calculated using the direct method. Results: The age-standardised incidence rate of stomach cancer in Aomori prefecture was higher than in the whole of Japan for males but lower for females. However, the age-standardised mortality rates were higher in Aomori prefecture in both sexes. The proportion of localised cancers was lower in Aomori prefecture than in the whole of Japan for most age groups. Conclusions: The lower rate for localised cancer suggests that higher age-standardised mortality rates are due to delays in diagnosis, despite an attendance rate for stomach cancer screening was higher in Aomori prefecture than in the whole of Japan. One plausible explanation for the failure of successful early detection might be poor quality control during screening implementation that impedes early detection.

  17. 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.

  18. Homozygous mdm2 SNP309 cancer cells with compromised transcriptional elongation at p53 target genes are sensitive to induction of p53-independent cell death.

    Science.gov (United States)

    Rosso, Melissa; Polotskaia, Alla; Bargonetti, Jill

    2015-10-27

    A single nucleotide polymorphism (T to G) in the mdm2 P2 promoter, mdm2 SNP309, leads to MDM2 overexpression promoting chemotherapy resistant cancers. Two mdm2 G/G SNP309 cancer cell lines, MANCA and A875, have compromised wild-type p53 that co-localizes with MDM2 on chromatin. We hypothesized that MDM2 in these cells inhibited transcription initiation at the p53 target genes p21 and puma. Surprisingly, following etoposide treatment transcription initiation occurred at the compromised target genes in MANCA and A875 cells similar to the T/T ML-1 cell line. In all cell lines tested there was equally robust recruitment of total and initiated RNA polymerase II (Pol II). We found that knockdown of MDM2 in G/G cells moderately increased expression of subsets of p53 target genes without increasing p53 stability. Importantly, etoposide and actinomycin D treatments increased histone H3K36 trimethylation in T/T, but not G/G cells, suggesting a G/G correlated inhibition of transcription elongation. We therefore tested a chemotherapeutic agent (8-amino-adenosine) that induces p53-independent cell death for higher clinically relevant cytotoxicity. We demonstrated that T/T and G/G mdm2 SNP309 cells were equally sensitive to 8-amino-adenosine induced cell death. In conclusion for cancer cells overexpressing MDM2, targeting MDM2 may be less effective than inducing p53-independent cell death.

  19. Hispolon from Phellinus linteus induces apoptosis and sensitizes human cancer cells to the tumor necrosis factor-related apoptosis-inducing ligand through upregulation of death receptors.

    Science.gov (United States)

    Kim, Ji-Hun; Kim, Yu Chul; Park, Byoungduck

    2016-02-01

    The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent anticancer agent possessing the ability to induce apoptosis in various cancer cells but not in non‑malignant cells. However, certain type of cancer cells are resistant to TRAIL‑induced apoptosis and some acquire resistance after the first treatment. So development of an agent that can reduce or avoid resistance in TRAIL‑induced apoptosis has garnered significant attention. The present study evaluated the anticancer potential of hispolon in TRAIL‑induced apoptosis and indicated hispolon can sensitize cancer cells to TRAIL. As the mechanism of action was examined, hispolon was found to activate caspase‑3, caspase‑8 and caspase‑9, while downregulating the expression of cell survival proteins such as cFLIP, Bcl‑2 and Bcl‑xL and upregulating the expression of Bax and truncated Bid. We also found hispolon induced death receptors in a non‑cell type‑specific manner. Upregulation of death receptors by hispolon was found to be p53-independent but linked to the induction of CAAT enhancer binding protein homologous protein (CHOP). Overall, hispolon was demonstrated to potentiate the apoptotic effects of TRAIL through downregulation of anti‑apoptotic proteins and upregulation of death receptors linked with CHOP and pERK elevation.

  20. Forecasting Age-Specific Brain Cancer Mortality Rates Using Functional Data Analysis Models

    Directory of Open Access Journals (Sweden)

    Keshav P. Pokhrel

    2015-01-01

    Full Text Available Incidence and mortality rates are considered as a guideline for planning public health strategies and allocating resources. We apply functional data analysis techniques to model age-specific brain cancer mortality trend and forecast entire age-specific functions using exponential smoothing state-space models. The age-specific mortality curves are decomposed using principal component analysis and fit functional time series model with basis functions. Nonparametric smoothing methods are used to mitigate the existing randomness in the observed data. We use functional time series model on age-specific brain cancer mortality rates and forecast mortality curves with prediction intervals using exponential smoothing state-space model. We also present a disparity of brain cancer mortality rates among the age groups together with the rate of change of mortality rates. The data were obtained from the Surveillance, Epidemiology and End Results (SEER program of the United States. The brain cancer mortality rates, classified under International Classification Disease code ICD-O-3, were extracted from SEER*Stat software.

  1. 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...

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Impact of the 1998 football World Cup on suicide rates in France: results from the national death registry.

    Science.gov (United States)

    Encrenaz, Gaëlle; Contrand, Benjamin; Leffondré, Karen; Queinec, Raphaëlle; Aouba, Albertine; Jougla, Eric; Miras, Alain; Lagarde, Emmanuel

    2012-04-01

    Our objective was to determine whether the Fédération 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; France). These data were analyzed using the seasonal ARIMA model. The overall effect of the World Cup was tested together with potential specific impact on days following the French team games. Between 11th June and 11th July, a significant decline of 95 suicides was observed (-10.3%), this effect being the strongest among men and people aged between 30 and 44. A significant decrease was also observed for the days following French team games (-19.9%). Our results are in favor of an effect of nationwide sport events on suicidal behaviors and are consistent with other studies. Many of the theories explaining the relationship between sports and suicide are related to sense of belongingness and social integration, highlighting the importance of social link reinforcement in suicide prevention.

  7. CT Measures of Bone Mineral Density and Muscle Mass Can Be Used to Predict Noncancer Death in Men with Prostate Cancer.

    Science.gov (United States)

    McDonald, Andrew M; Swain, Thomas A; Mayhew, David L; Cardan, Rex A; Baker, Christopher B; Harris, David M; Yang, Eddy S; Fiveash, John B

    2017-02-01

    Purpose To determine if computed tomographic (CT) metrics of bone mineral density and muscle mass can improve the prediction of noncancer death in men with localized prostate cancer. Materials and Methods Institutional review board approval was obtained, with waiver of informed consent. All patients who underwent radiation therapy for localized prostate cancer between 2001 and 2012 with height, weight, and past medical history documented and who underwent CT that included the L4-5 vertebral interspace were included. On a single axial CT section obtained at the mid-L5 level, the mean CT attenuation of the trabecular bone of the L5 vertebral body (L5HU) was measured. The height-normalized psoas cross-sectional area (PsoasL4-5) was measured on a single CT section obtained at the L4-5 vertebral interface. Multivariable Cox proportional hazards models were used to assess effects on noncancer death. By using parameter estimates from an adjusted model, a prognostic index for prediction of noncancer death was generated and compared with age-adjusted Charlson Comorbidity Index (CCI) by using the Harrell c statistic. Results Six hundred fifty-three men met the inclusion criteria. Prostate cancer risk grouping, androgen deprivation, race, age-adjusted CCI, L5HU, and PsoasL4-5 were included in a multivariable model. Age-adjusted CCI (hazard ratio [HR] = 1.36, P < .001), L5HU (HR = 2.88 for L5HU < 105 HU, HR = 1.42 for 105 HU ≤ L5HU ≤ 150 HU, P < .001), PsoasL4-5 (HR = 1.95 for PsoasL4-5 < 7.5 cm(2)/m(2), P = .003), and race (HR = 1.68 for African American race, HR = 1.77 for other nonwhite race, P = .019) were independent predictors of noncancer death. The prognostic index yielded a c value of 0.747 for the prediction of noncancer death versus 0.718 for age-adjusted CCI alone. Conclusion L5HU and PsoasL4-5, which are surrogates for bone mineral density and muscle mass, respectively, were independent predictors of noncancer death. The prognostic index that incorporated

  8. Effects of Rational-Emotive Hospice Care Therapy on Problematic Assumptions, Death Anxiety, and Psychological Distress in a Sample of Cancer Patients and Their Family Caregivers in Nigeria

    Directory of Open Access Journals (Sweden)

    Kay Chinonyelum Nwamaka Onyechi

    2016-09-01

    Full Text Available This study was a preliminary investigation that aimed to examine the effects of rational emotive hospice care therapy (REHCT on problematic assumptions, death anxiety, and psychological distress in a sample of cancer patients and their family caregivers in Nigeria. The study adopted a pre-posttest randomized control group design. Participants were community-dwelling cancer patients (n = 32 and their family caregivers (n = 52. The treatment process consisted of 10 weeks of full intervention and 4 weeks of follow-up meetings that marked the end of intervention. The study used repeated-measures analysis of variance for data analysis. The findings revealed significant effects of a REHCT intervention program on problematic assumptions, death anxiety, and psychological distress reduction among the cancer patients and their family caregivers at the end of the intervention. The improvements were also maintained at follow-up meetings in the treatment group compared with the control group who received the usual care and conventional counseling. The researchers have been able to show that REHCT intervention is more effective than a control therapy for cancer patients’ care, education, and counseling in the Nigerian context.

  9. Brain death.

    Science.gov (United States)

    Wijdicks, Eelco F M

    2013-01-01

    The diagnosis of brain death should be based on a simple premise. If every possible confounder has been excluded and all possible treatments have been tried or considered, irreversible loss of brain function is clinically recognized as the absence of brainstem reflexes, verified apnea, loss of vascular tone, invariant heart rate, and, eventually, cardiac standstill. This condition cannot be reversed - not even partly - by medical or surgical intervention, and thus is final. Many countries in the world have introduced laws that acknowledge that a patient can be declared brain-dead by neurologic standards. The U.S. law differs substantially from all other brain death legislation in the world because the U.S. law does not spell out details of the neurologic examination. Evidence-based practice guidelines serve as a standard. In this chapter, I discuss the history of development of the criteria, the current clinical examination, and some of the ethical and legal issues that have emerged. Generally, the concept of brain death has been accepted by all major religions. But patients' families may have different ideas and are mostly influenced by cultural attitudes, traditional customs, and personal beliefs. Suggestions are offered to support these families.

  10. 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.

  11. Unfavorable survival rates in Iranian patients with gastric cancers: a single center experience from Tehran.

    Directory of Open Access Journals (Sweden)

    Hossein Khedmat

    2014-03-01

    Full Text Available We examined the effect of potential interfering factors that play major roles in the outcome of our patients with stomach cancer. 100 consecutive patients diagnosed with gastric cancers were prospectively observed, treated and followed from November 2009 to January. Absence of Helicobacter pylori infection (P=0.027, absence of vascularisation (P<0.001, and undetermined histopathological type of adenocarcinoma (P=0.003 were factors significantly associated with higher grade of gastric lesions. Life tables were used to define survival of gastric cancers. Survival rates of these patients at 1st week, 1st month, 2nd month, 3rd month, and 6th month were 97%, 96%, 91%, 90%, and 82%, respectively. The only determinant of 6 months of survival was age over 68 (P=0.039. Our study confirms our previous knowledge that gastric cancers have unfavorable outcome in Iran.

  12. Acute cell death rate of vascular smooth muscle cells during or after short heating up to 20s ranging 50 to 60°C as a basic study of thermal angioplasty

    Science.gov (United States)

    Shinozuka, Machiko; Shimazaki, Natsumi; Ogawa, Emiyu; Machida, Naoki; Arai, Tsunenori

    2014-02-01

    We studied the relations between the time history of smooth muscle cells (SMCs) death rate and heating condition in vitro to clarify cell death mechanism in heating angioplasty, in particular under the condition in which intimal hyperplasia growth had been prevented in vivo swine experiment. A flow heating system on the microscope stage was used for the SMCs death rate measurement during or after the heating. The cells were loaded step-heating by heated flow using a heater equipped in a Photo-thermo dynamic balloon. The heating temperature was set to 37, 50-60°C. The SMCs death rate was calculated by a division of PI stained cell number by Hoechst33342 stained cell number. The SMCs death rate increased 5-10% linearly during 20 s with the heating. The SMCs death rate increased with duration up to 15 min after 5 s heating. Because fragmented nuclei were observed from approximately 5 min after the heating, we defined that acute necrosis and late necrosis were corresponded to within 5 min after the heating and over 5 min after the heating, respectively. This late necrosis is probably corresponding to apoptosis. The ratio of necrotic interaction divided the acute necrosis rate by the late necrosis was calculated based on this consideration as 1.3 under the particular condition in which intimal hyperplasia growth was prevented in vivo previous porcine experiment. We think that necrotic interaction rate is larger than expected rate to obtain intimal hyperplasia suppression.

  13. 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...

  14. 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...

  15. 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.

  16. Bleomycin induced sensitivity to TRAIL/Apo-2L-mediated apoptosis in human seminomatous testicular cancer cells is correlated with upregulation of death receptors.

    Science.gov (United States)

    Timur, Mujgan; Cort, Aysegul; Ozdemir, Evrim; Sarikcioglu, Sureyya Bilmen; Sanlioglu, Salih; Sanlioglu, Ahter Dilsad; Ozben, Tomris

    2015-01-01

    The most common solid tumor is testicular cancer among young men. Bleomycin is an antitumor antibiotic used for the therapy of testicular cancer. TRAIL is a proapoptotic cytokine that qualified as an apoptosis inducer in cancer cells. Killing cancer cells selectively via apoptosis induction is an encouraging therapeutic strategy in clinical settings. Combination of TRAIL with chemotherapeutics has been reported to enhance TRAIL-mediated apoptosis of different kinds of cancer cell lines. The molecular ground for sensitization of tumour cells to TRAIL by chemotherapeutics might involve upregulation of TRAIL-R1 (TR/1, DR4) and/or TRAIL-R2 (TR/2, DR5) receptors or activation of proapoptotic proteins including caspases. The curative potential of TRAIL to eradicate cancer cells selectively in testicular cancer has not been studied before. In this study, we investigated apoptotic effects of bleomycin, TRAIL, and their combined application in NTera-2 and NCCIT testicular cancer cell lines. We measured caspase 3 levels as an apoptosis indicator, and TRAIL receptor expressions using flow cytometry. Both NTera-2 and NCCIT cells were fairly resistant to TRAIL's apoptotic effect. Incubation of bleomycin alone caused a significant increase in caspase 3 activity in NCCIT. Combined incubation with bleomycin and TRAIL lead to elevated caspase 3 activity in Ntera-2. Exposure to 72 h of bleomycin increased TR/1, TR/2, and TR/3 cell-surface expressions in NTera-2. Elevation in TR/1 cell-surface expression was evident only at 24 h of bleomycin application in NCCIT. It can be concluded that TRAIL death receptor expressions in particular are increased in testicular cancer cells via bleomycin treatment, and TRAIL-induced apoptosis is initiated.

  17. Investigation of anticancer effect of Xanthoceraside in vitro and the mechanism of Xanthoceraside-induced human breast cancer MCF-7 cell death

    Institute of Scientific and Technical Information of China (English)

    JI Xue-fei; XIA Ming-yu; CHI Tian-yan; WANG Li-hua; YANG Bai-zhen; ZOU Li-bo

    2008-01-01

    Objective To investigate the anticancer effect of xanthoceraside in vitro and the possible mechanisms involved in the potent antiproliferative effect on human breast cancer MCF-7 cell. Methods The inhibition rate of different tumor cells and human peripheral blood lymphocyte cells was investigated by MTT assay. AO/EB double fluorescent dye staining was used to investigate the morphology changes of MCF-7. The DNA agarose gel electrophoresis was further used to observe the DNA Fragmentation. Flow eytometry was employed to investigate the volume changes, the cell cycle distribution and the mitoehondrial membrane potential of MCF-7. The antioxidant N-acetylcysteine (NAC) was chosen to detect the influence on oxidantstress system of MCF-7 cells. Necrostatin-1 was next chosen to detect the influence on antiproliferative effect of xanthoceraside-treated MCF-7 cells. Results Xanthoceraside could inhibit the proliferation of tumor cells significantly in a dose-dependent manner and it has no eytotoxie effects on human peripheral blood lymphocyte cells in vitro. Cytoplasm vacuole was observed but no significant condense of nuclear ehromatin was found, meanwhile, MCF-7 cells were bigger and smear was observed by agarose gel electrophoresis after MCF-7 cells were exposed to xanthoceraside. The cell cycle distribution of MCF-7 was greatly changed after exposure to xanthoceraside with an obvious G1 arrest. The mitochondrial membrane potential showed significant decrease. NAC attenuate the antiproliferative effect of xanthoceraside-treated MCF-7 cells but necrostatin-1 had no effects. Conclnsions Xanthoceraside-indueed necrosis might be dependent of mitochondria, meanwhile reactive oxygen species (ROS) participated in it. The xanthoceraside-indueed MCF-7 cell death might not be the cell necrosis which initiated by Fas/TNFR and must be through RIP1 kinase.

  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. 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.

  20. ``In Vivo'' Dosimetry in High Dose Rate Brachytherapy for Cervical Cancer Treatments

    Science.gov (United States)

    González-Azcorra, S. A.; Mota-García, A.; Poitevín-Chacón, M. A.; Santamaría-Torruco, B. J.; Rodríguez-Ponce, M.; Herrera-Martínez, F. P.; Gamboa de Buen, I.; Ruíz-Trejo, C.; Buenfil, A. E.

    2008-08-01

    In this prospective study, rectal dose was measured "in vivo" using TLD-100 crystals (3×3×1 mm3), and it has been compared to the prescribed dose. Measurements were performed in patients with cervical cancer classified in FIGO stages IB-IIIB and treated with high dose rate brachytherapy (HDR BT) at the Instituto Nacional de Cancerología (INCan).

  1. Axillary recurrence rate 5 years after negative sentinel node biopsy for breast cancer

    NARCIS (Netherlands)

    Andersson, Y.; de Boniface, J.; Jonsson, P. -E.; Ingvar, C.; Liljegren, G.; Bergkvist, L.; Frisell, J.

    2012-01-01

    Background: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection (ALND) as the standard axillary staging procedure in breast cancer. Follow-up studies in SLN-negative women treated without ALND report low rates of axillary recurrence, but most studies have short follow-up, an

  2. Trends in Cancer Screening Rates among Korean Men and Women: Results from the Korean National Cancer Screening Survey (KNCSS), 2004-2010

    OpenAIRE

    Lee, Eun-Ha; Lee, Hoo-Yeon; Choi, Kui Son; Jun, Jae Kwan; Park, Eun-Cheol; Lee, Jin Soo

    2011-01-01

    Purpose The Korean National Cancer Screening Survey (KNCSS) is a continuous nationwide survey implemented by the National Cancer Center in Korea since 2004. The purpose of the present study was to report trends in cancer screening rates for the five major cancers (stomach, liver, colorectal, breast, and cervix uteri) in Korean men and women. Materials and Methods The study used KNCSS data collected between 2004 and 2010. The survey was conducted on Korean men aged 40-74 years and Korean women...

  3. 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.

  4. Lung Cancer Statistics.

    Science.gov (United States)

    Torre, Lindsey A; Siegel, Rebecca L; Jemal, Ahmedin

    2016-01-01

    Lung cancer is the leading cause of cancer death among both men and women in the United States. It is also the leading cause of cancer death among men and the second leading cause of cancer death among women worldwide. Lung cancer rates and trends vary substantially by sex, age, race/ethnicity, socioeconomic status, and geography because of differences in historical smoking patterns. Lung cancer mortality rates in the United States are highest among males, blacks, people of lower socioeconomic status, and in the mid-South (e.g., Kentucky, Mississippi, Arkansas, and Tennessee). Globally, rates are highest in countries where smoking uptake began earliest, such as those in North America and Europe. Although rates are now decreasing in most of these countries (e.g., United States, United Kingdom, Australia), especially in men, they are increasing in countries where smoking uptake occurred later. Low- and middle-income countries now account for more than 50% of lung cancer deaths each year. This chapter reviews lung cancer incidence and mortality patterns in the United States and globally.

  5. MiR-193b promotes autophagy and non-apoptotic cell death in oesophageal cancer cells

    NARCIS (Netherlands)

    J. Nyhan (Michelle); R. O'Donovan (Tracey); W.M.A. Boersma (Antonius); E.A.C. Wiemer (Erik); S.L. McKenna (Sharon)

    2016-01-01

    markdownabstract__Background:__ Successful treatment of oesophageal cancer is hampered by recurrent drug resistant disease. We have previously demonstrated the importance of apoptosis and autophagy for the recovery of oesophageal cancer cells following drug treatment. When apoptosis (with autophagy)

  6. 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.

  7. Increased rate change over time of a sphincter-saving procedure for lower rectal cancer

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-jian; WANG Jian-ping; WANG Lei; HE Xiao-sheng; ZOU Yi-feng; LIAN Lei; ZHANG Long-juan; LAN Ping

    2008-01-01

    Background Total mesorectal excision(TME)has increased the rate of sphincter-preservation(SP)for more patients with low-lying rectal cancer.Here,we analyze the change of sphincter preserving rates in lower rectal cancer and their related factors.Methods We reviewed retrospectively the medical records of 316 patients with lower rectal cancers,1 to 5 cm from the anorectal line,who had surgical resections from August 1994 to November 2005.The 12-year span was divided into 2 periods:period Ⅰ(August 1994-December 1998)and period Ⅱ(January 1999-November 2005),based on the date (January 1999)when standard total mesorectal excision(TME)was introduced.The patients were divided jnto two groups based on the operation:abdominoperineal resection(APR)or SP surgery.SP rates,leakage and other clinicopathological characteristics were compared between the two time periods and between the two different groups.Results The SP rate increased significantly over the 12 years,from 44.9% in period Ⅰ to 76.2% in period Ⅱ(P=0.000).The factors significantly influencing SP included the distance of the tumor from the anorectal line,gender,time period,circumference of intramural spread and histological differentiation (P<0.05).Significant differences were detected between the two time periods in gender,blood transfusion volume and Dukes'stage(P<0.05).The leakage rate was 2.7% in period Ⅰ and 1.3% in period Ⅱ (P>0.05).Conclusions Over the 12-year period of the study the SP rate in rectal cancers 1-5 cm from the anorectal line has increased significantly while the blood transfusion volume has decreased due to the introduction of TME.However,TME had no effect on operating time and leakage rates.

  8. Frankincense derived heavy terpene cocktail boosting breast cancer cell (MDA-MB-231 death in vitro

    Directory of Open Access Journals (Sweden)

    Faruck Lukmanul Hakkim

    2015-10-01

    Conclusions: Extracting anti-cancer active principle cocktail by simple Soxhlet method is cost effective and less time consuming. Our in vitro anti-cancer data forms the rationale for us to test heavy terpene complex in breast cancer xenograft model in vivo. Furthermore, fractionation and developing frankincense heavy terpene based breast cancer drug is the major goal of our laboratory.

  9. 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...

  10. Annual Report to the Nation on the Status of Cancer, 1975–2010

    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.

  11. Programmed cell death 2 protein induces gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis in a p53-dependent manner.

    Science.gov (United States)

    Zhang, Jian; Wei, Wei; Jin, Hui-Cheng; Ying, Rong-Chao; Zhu, A-Kao; Zhang, Fang-Jie

    2015-01-01

    Programmed cell death 2 (PDCD2) is a highly conserved nuclear protein, and aberrant PDCD2 expression alters cell apoptosis. The present study aimed to investigate PDCD2 expression in gastric cancer. Tissue specimens from 34 gastric cancer patients were collected for analysis of PDCD2 expression using immunohistochemistry, western blotting and qRT-PCR. Gastric cancer cell lines (a p53-mutated MKN28 line and a wild-type p53 MKN45 line) were used to assess the effects of PDCD2 overexpression. p53-/- nude mice were used to investigate the effect of PDCD2 on ultraviolet B (UVB)-induced skin carcinogenesis. The data showed that PDCD2 expression was reduced in gastric cancer tissue specimens, and loss of PDCD2 expression was associated with the poor survival of patients. PDCD2 expression induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis. The antitumor effects of PDCD2 expression were dependent on p53 expression in gastric cancer cells. Moreover, PDCD2 expression inhibited activity of the ATM/Chk1/2/p53 signaling pathway. In addition, PDCD2 expression suppressed UVB-induced skin carcinogenesis in p53+/+ nude mice, but not in p53-/- mice. The data from the present study demonstrated that loss of PDCD2 expression could contribute to gastric cancer development and progression and that PDCD2-induced gastric cancer cell growth arrest at the early S phase of the cell cycle and apoptosis are p53-dependent.

  12. The Causes and Risk Factors of Tuberculosis Deaths in Khuzestan

    Directory of Open Access Journals (Sweden)

    Alavi Seyed Mohammad

    2009-05-01

    Full Text Available Tuberculosis (TB is one of the 10 leading cause of deaths in developing countries. Understanding the cause and risk factors of TB death and lowering them can reduce its mortality rate. The aim of this study was to assess the cause and risk factors for death of tuberculosis. A retrospective descriptive study was conducted in Khuzestan province in the south west of Iran, from 2002 to 2006. Medical records of tuberculosis cases over the 5-year period were reviewed and death data were analyzed. Including criteria were documented TB diagnosed based on National Tuberculosis Program (NTP. Extracted data were analyzed in SPSS 11.5 system and by chi squared test. One hundred and twenty five deaths (3.15% with mean age of 48.96±10.03 years were detected. Risk factors for death were: cigarette smoking, diabetes, chronic peritoneal dialysis, MDR-TB, imprisonment, AIDS and injection drug usage. 93 deaths (74.4% were directly attributed to tuberculosis. Overwhelming TB disease, hemoptysis, AIDS/HIV and MDR-TB were the cause of death with the rate of 69.9%, 11.8%, 9.7% and 8.6%, respectively. 32 (25.6% deaths were due to medical problems unrelated to TB, among which were cardiovascular diseases, bacterial super infection and cancers with the rate of 25%, 21.9% and 15.6%, respectively. The deaths of TB not only are directly related to TB, but also are caused due to comorbid conditions. Overwhelming TB disease, hemoptysis, cardiovascular diseases, bacterial super infection and cancers are the main cause of death. MDR-TB, imprisonment, AIDS and injection drug usage are the main risk factors for TB mortality.

  13. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  14. 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.

  15. Analysis of stomach cancer mortality in the national retrospective sampling survey of death causes in China, 2004 - 2005%2004-2005年全国死因回顾抽样调查胃癌死亡率分析

    Institute of Scientific and Technical Information of China (English)

    邹小农; 段纪俊; 皇甫小梅; 陈万青; 赵平

    2010-01-01

    National Retrospective Sampling Survey of Death Causes in China, were analyzed and compared with the results from previous two national surveys. ResultsThe crude and age-standardized death rates of stomach cancer were 24. 71/100 000 (35 250/142 660 482) and 16. 16/100 000,respectively,accounted for 18. 19% (35 250/193 841) and ranking third of cancer causes in the national sampling areas of China in 2004 -2005. Those crude death rate increased by 42.01% while the age-standardized death rate decreased by 8. 70% compared to the results in 1973 - 1975 (17.40/100 000 and 17.70/100 000), and both decreased 1.79% and 25.74% from 1990 - 1992 (25. 16/100 000 and 21.76/100 000), respectively. For urban residents of the sampling areas, the crude and age-standardized death rates of stomach cancer were 22.98/100 000 (11 005/47 899 806) and 13.63/100 000, accounted for 15.03 % (11 005/71 936) of cancer causes in 2004 - 2005, which increased by 18.21% and decreased by 31.16% from 1973 -1975 (19.44/100 000 and 19.80/100 O00),and increased by 18. 21% and decreased by 11.15% from 1990 - 1992 (19. 44/100 000 and 15.34/100 000), respectively. While for rural residents in the sampling areas, the crude and age-standardized death rates were 25.59/100000 (24 245/94 760 676) and 17.64/100 000,accounted for 19.89% (24 245/121 905) of cancer causes, both increased by 53.97% and 3.76% from 1973 - 1975 (16. 62/100 000 and 17.00/100 000),and both decreased by 5.78% and 27,59% from 1990 - 1992 (27. 16/100 000 and 24. 36/100 000) ,respectively. Conclusion The current stomach cancer is still one of predominant cancers in China. The consistently substantial decreases in age-standardized death rates of stomach cancer might prompt the beneficial impact on reducing the risks for that cancer by the social economical development during recent decades in China.

  16. Reducing Potentially Excess Deaths from the Five Leading Causes of Death in the Rural United States

    Science.gov (United States)

    Garcia, Macarena C; Faul, Mark; Massetti, Greta; Thomas, Cheryll C; Hong, Yuling; Bauer, Ursula E; Iademarco, Michael F

    2017-01-13

    In 2014, the all-cause age-adjusted death rate in the United States reached a historic low of 724.6 per 100,000 population (1). However, mortality in rural (nonmetropolitan) areas of the United States has decreased at a much slower pace, resulting in a widening gap between rural mortality rates (830.5) and urban mortality rates (704.3) (1). During 1999–2014, annual age-adjusted death rates for the five leading causes of death in the United States (heart disease, cancer, unintentional injury, chronic lower respiratory disease (CLRD), and stroke) were higher in rural areas than in urban (metropolitan) areas (Figure 1). In most public health regions (Figure 2), the proportion of deaths among persons aged rural areas compared with urban areas (Figure 3). Several factors probably influence the rural-urban gap in potentially excess deaths from the five leading causes, many of which are associated with sociodemographic differences between rural and urban areas. Residents of rural areas in the United States tend to be older, poorer, and sicker than their urban counterparts (3). A higher proportion of the rural U.S. population reports limited physical activity because of chronic conditions than urban populations (4). Moreover, social circumstances and behaviors have an impact on mortality and potentially contribute to approximately half of the determining causes of potentially excess deaths (5).

  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. Changes in causes of death among persons with AIDS: San Francisco, California, 1996-2011.

    Science.gov (United States)

    Schwarcz, Sandra K; Vu, Annie; Hsu, Ling Chin; Hessol, Nancy A

    2014-10-01

    The increased life expectancy among HIV-infected persons treated with combination antiretroviral therapy (ART), risk behaviors, and co-morbidities associated with ART place HIV-infected persons at risk for non-HIV-related causes of death. We used the San Francisco HIV/AIDS registry to identify deaths that occurred from January 1996 through December 2011. Temporal trends in AIDS- and non-AIDS-related mortality rates, the proportion of underlying and contributory causes of death, and the ratio of observed deaths in the study population to expected number of deaths among California men aged 20-79 (standardized mortality ratio [SMR]) of underlying causes of death were examined. A total of 5338 deaths were identified. The annual AIDS-related death rate (per 100 deaths) declined from 10.8 in 1996 to 0.9 in 2011 (p<0.0001), while the annual death rate from non-AIDS-related causes declined from 2.1 in 1996 to 0.9 in 2011 (p<0.0001). The proportion of deaths due to all types of heart disease combined, all non-AIDS cancers combined, mental disorders resulting from substance abuse, drug overdose, suicide and chronic obstructive pulmonary disease increased significantly over time. The SMRs for liver diseased decreased significantly over time but remained elevated. Our data highlight the importance of age-related causes of death as well as deaths from causes that are, at least in part, preventable.

  19. 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

  20. 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