Local bladder cancer clusters in southeastern Michigan accounting for risk factors, covariates and residential mobility.

Directory of Open Access Journals (Sweden)

Geoffrey M Jacquez

Full Text Available In case control studies disease risk not explained by the significant risk factors is the unexplained risk. Considering unexplained risk for specific populations, places and times can reveal the signature of unidentified risk factors and risk factors not fully accounted for in the case-control study. This potentially can lead to new hypotheses regarding disease causation.Global, local and focused Q-statistics are applied to data from a population-based case-control study of 11 southeast Michigan counties. Analyses were conducted using both year- and age-based measures of time. The analyses were adjusted for arsenic exposure, education, smoking, family history of bladder cancer, occupational exposure to bladder cancer carcinogens, age, gender, and race.Significant global clustering of cases was not found. Such a finding would indicate large-scale clustering of cases relative to controls through time. However, highly significant local clusters were found in Ingham County near Lansing, in Oakland County, and in the City of Jackson, Michigan. The Jackson City cluster was observed in working-ages and is thus consistent with occupational causes. The Ingham County cluster persists over time, suggesting a broad-based geographically defined exposure. Focused clusters were found for 20 industrial sites engaged in manufacturing activities associated with known or suspected bladder cancer carcinogens. Set-based tests that adjusted for multiple testing were not significant, although local clusters persisted through time and temporal trends in probability of local tests were observed.Q analyses provide a powerful tool for unpacking unexplained disease risk from case-control studies. This is particularly useful when the effect of risk factors varies spatially, through time, or through both space and time. For bladder cancer in Michigan, the next step is to investigate causal hypotheses that may explain the excess bladder cancer risk localized to areas of

Neoadjuvant chemoradiotherapy plus surgery versus active surveillance for oesophageal cancer: a stepped-wedge cluster randomised trial.

Science.gov (United States)

Noordman, Bo Jan; Wijnhoven, Bas P L; Lagarde, Sjoerd M; Boonstra, Jurjen J; Coene, Peter Paul L O; Dekker, Jan Willem T; Doukas, Michael; van der Gaast, Ate; Heisterkamp, Joos; Kouwenhoven, Ewout A; Nieuwenhuijzen, Grard A P; Pierie, Jean-Pierre E N; Rosman, Camiel; van Sandick, Johanna W; van der Sangen, Maurice J C; Sosef, Meindert N; Spaander, Manon C W; Valkema, Roelf; van der Zaag, Edwin S; Steyerberg, Ewout W; van Lanschot, J Jan B

2018-02-06

Neoadjuvant chemoradiotherapy (nCRT) plus surgery is a standard treatment for locally advanced oesophageal cancer. With this treatment, 29% of patients have a pathologically complete response in the resection specimen. This provides the rationale for investigating an active surveillance approach. The aim of this study is to assess the (cost-)effectiveness of active surveillance vs. standard oesophagectomy after nCRT for oesophageal cancer. This is a phase-III multi-centre, stepped-wedge cluster randomised controlled trial. A total of 300 patients with clinically complete response (cCR, i.e. no local or disseminated disease proven by histology) after nCRT will be randomised to show non-inferiority of active surveillance to standard oesophagectomy (non-inferiority margin 15%, intra-correlation coefficient 0.02, power 80%, 2-sided α 0.05, 12% drop-out). Patients will undergo a first clinical response evaluation (CRE-I) 4-6 weeks after nCRT, consisting of endoscopy with bite-on-bite biopsies of the primary tumour site and other suspected lesions. Clinically complete responders will undergo a second CRE (CRE-II), 6-8 weeks after CRE-I. CRE-II will include 18F-FDG-PET-CT, followed by endoscopy with bite-on-bite biopsies and ultra-endosonography plus fine needle aspiration of suspected lymph nodes and/or PET- positive lesions. Patients with cCR at CRE-II will be assigned to oesophagectomy (first phase) or active surveillance (second phase of the study). The duration of the first phase is determined randomly over the 12 centres, i.e., stepped-wedge cluster design. Patients in the active surveillance arm will undergo diagnostic evaluations similar to CRE-II at 6/9/12/16/20/24/30/36/48 and 60 months after nCRT. In this arm, oesophagectomy will be offered only to patients in whom locoregional regrowth is highly suspected or proven, without distant dissemination. The main study parameter is overall survival; secondary endpoints include percentage of patients who do not

A Multidisciplinary Investigation of a Polycythemia Vera Cancer Cluster of Unknown Origin

Science.gov (United States)

Seaman, Vincent; Dearwent, Steve M; Gable, Debra; Lewis, Brian; Metcalf, Susan; Orloff, Ken; Tierney, Bruce; Zhu, Jane; Logue, James; Marchetto, David; Ostroff, Stephen; Hoffman, Ronald; Xu, Mingjiang; Carey, David; Erlich, Porat; Gerhard, Glenn; Roda, Paul; Iannuzzo, Joseph; Lewis, Robert; Mellow, John; Mulvihill, Linda; Myles, Zachary; Wu, Manxia; Frank, Arthur; Gross-Davis, Carol Ann; Klotz, Judith; Lynch, Adam; Weissfeld, Joel; Weinberg, Rona; Cole, Henry

2010-01-01

Cancer cluster investigations rarely receive significant public health resource allocations due to numerous inherent challenges and the limited success of past efforts. In 2008, a cluster of polycythemia vera, a rare blood cancer with unknown etiology, was identified in northeast Pennsylvania. A multidisciplinary group of federal and state agencies, academic institutions, and local healthcare providers subsequently developed a multifaceted research portfolio designed to better understand the cause of the cluster. This research agenda represents a unique and important opportunity to demonstrate that cancer cluster investigations can produce desirable public health and scientific outcomes when necessary resources are available. PMID:20617023

miR-206/133b Cluster: A Weapon against Lung Cancer?

Directory of Open Access Journals (Sweden)

Jing-Yu Pan

2017-09-01

Full Text Available Lung cancer is a deadly disease that ends numerous lives around the world. MicroRNAs (miRNAs are a group of non-coding RNAs involved in a variety of biological processes, such as cell growth, organ development, and tumorigenesis. The miR-206/133b cluster is located on the human chromosome 6p12.2, which is essential for growth and rebuilding of skeletal muscle. The miR-206/133b cluster has been verified to be dysregulated and plays a crucial role in lung cancer. miR-206 and miR-133b participate in lung tumor cell apoptosis, proliferation, migration, invasion, angiogenesis, drug resistance, and cancer treatment. The mechanisms are sophisticated, involving various target genes and molecular pathways, such as MET, EGFR, and the STAT3/HIF-1α/VEGF signal pathway. Hence, in this review, we summarize the role and potential mechanisms of the miR-206/133b cluster in lung cancer. Keywords: lung cancer, miR-206/133b cluster, miR-206, miR-133b

Symptom Clusters and Quality of Life in Hospice Patients with Cancer

Science.gov (United States)

Omran, Suha; Khader, Yousef; McMillan, Susan

2017-09-27

Background: Symptom control is an important part of palliative care and important to achieve optimal quality of life (QOL). Studies have shown that patients with advanced cancer suffer from diverse and often severe physical and psychological symptoms. The aim is to explore the influence of symptom clusters on QOL among patients with advanced cancer. Materials and Methods: 709 patients with advanced cancer were recruited to participate in a clinical trial focusing on symptom management and QOL. Patients were adults newly admitted to hospice home care in one of two hospices in southwest Florida, who could pass mental status screening. The instruments used for data collection were the Demographic Data Form, Memorial Symptom Assessment Scale (MSAS), and the Hospice Quality of Life Index-14. Results: Exploratory factor analysis and multiple regression were used to identify symptom clusters and their influence on QOL. The results revealed that the participants experienced multiple concurrent symptoms. There were four symptom clusters found among these cancer patients. Individual symptom distress scores that were the strongest predictors of QOL were: feeling pain; dry mouth; feeling drowsy; nausea; difficulty swallowing; worrying and feeling nervous. Conclusions: Patients with advanced cancer reported various concurrent symptoms, and these form symptom clusters of four main categories. The four symptoms clusters have a negative influence on patients’ QOL and required specific care from different members of the hospice healthcare team. The results of this study should be used to guide health care providers’ symptom management. Proper attention to symptom clusters should be the basis for accurate planning of effective interventions to manage the symptom clusters experienced by advanced cancer patients. The health care provider needs to plan ahead for these symptoms and manage any concurrent symptoms for successful promotion of their patient’s QOL. Creative Commons

Identification of symptom clusters in cancer patients at palliative care clinic

Directory of Open Access Journals (Sweden)

Gülçin Senel Özalp

2017-01-01

Full Text Available Objective: Cancer patients often experience a large number of symptoms together. The aim of this study is to determine the symptom clusters in cancer patients at palliative care clinic. Methods: Hundred and seventy consecutive patients were enrolled in the study. Memorial Symptom Assessment Scale was used for symptom assessment of the patients. Results: The most experienced symptoms by the patients during the past week before hospitalization in palliative care clinic were lack of energy (95.4%, weight loss (91.2%, lack of appetite (89.4%, pain (88.2%, dry mouth (87.6%, feeling sad (87.6%, feeling nervous (82.9%, worrying (81.2%, and feeling irritable (80.6%. Five symptom clusters were defined. First cluster: pain, feeling nervous, dry mouth, worrying, feeling irritable, weight loss; second cluster: feeling drowsy, numbness/tingling in hands/feet, difficulty in sleeping, dizziness, constipation, I do not look like myself; third cluster: nausea, vomiting; fourth cluster: shortness of breath, difficulty in swallowing, cough, change in the way food tastes; and fifth cluster: feeling bloated, problems with urination, diarrhea, itching, mouth sores, hair loss, swelling of arm or legs, change in the skin. Conclusions: We encountered various symptom clusters in advanced cancer patients. Identification of symptom clusters and knowledge of cluster composition in oncological population may particularly contribute individualization of the treatment.

Determining the number of clusters for nuclei segmentation in breast cancer image

Science.gov (United States)

Fatichah, Chastine; Navastara, Dini Adni; Suciati, Nanik; Nuraini, Lubna

2017-02-01

Clustering is commonly technique for image segmentation, however determining an appropriate number of clusters is still challenging. Due to nuclei variation of size and shape in breast cancer image, an automatic determining number of clusters for segmenting the nuclei breast cancer is proposed. The phase of nuclei segmentation in breast cancer image are nuclei detection, touched nuclei detection, and touched nuclei separation. We use the Gram-Schmidt for nuclei cell detection, the geometry feature for touched nuclei detection, and combining of watershed and spatial k-Means clustering for separating the touched nuclei in breast cancer image. The spatial k-Means clustering is employed for separating the touched nuclei, however automatically determine the number of clusters is difficult due to the variation of size and shape of single cell breast cancer. To overcome this problem, first we apply watershed algorithm to separate the touched nuclei and then we calculate the distance among centroids in order to solve the over-segmentation. We merge two centroids that have the distance below threshold. And the new of number centroid as input to segment the nuclei cell using spatial k- Means algorithm. Experiment show that, the proposed scheme can improve the accuracy of nuclei cell counting.

The Role of Inflammation in the Pain, Fatigue, and Sleep Disturbance Symptom Cluster in Advanced Cancer.

Science.gov (United States)

Kwekkeboom, Kristine L; Tostrud, Lauren; Costanzo, Erin; Coe, Christopher L; Serlin, Ronald C; Ward, Sandra E; Zhang, Yingzi

2018-05-01

Symptom researchers have proposed a model of inflammatory cytokine activity and dysregulation in cancer to explain co-occurring symptoms including pain, fatigue, and sleep disturbance. We tested the hypothesis that psychological stress accentuates inflammation and that stress and inflammation contribute to one's experience of the pain, fatigue, and sleep disturbance symptom cluster (symptom cluster severity, symptom cluster distress) and its impact (symptom cluster interference with daily life, quality of life). We used baseline data from a symptom cluster management trial. Adult participants (N = 158) receiving chemotherapy for advanced cancer reported pain, fatigue, and sleep disturbance on enrollment. Before intervention, participants completed measures of demographics, perceived stress, symptom cluster severity, symptom cluster distress, symptom cluster interference with daily life, and quality of life and provided a blood sample for four inflammatory biomarkers (interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein). Stress was not directly related to any inflammatory biomarker. Stress and tumor necrosis factor-α were positively related to symptom cluster distress, although not symptom cluster severity. Tumor necrosis factor-α was indirectly related to symptom cluster interference with daily life, through its effect on symptom cluster distress. Stress was positively associated with symptom cluster interference with daily life and inversely with quality of life. Stress also had indirect effects on symptom cluster interference with daily life, through its effect on symptom cluster distress. The proposed inflammatory model of symptoms was partially supported. Investigators should test interventions that target stress as a contributing factor in co-occurring pain, fatigue, and sleep disturbance and explore other factors that may influence inflammatory biomarker levels within the context of an advanced cancer diagnosis and treatment

Taxonomical analysis of the Cancer cluster of galaxies

International Nuclear Information System (INIS)

Perea, J.; Olmo, A. del; Moles, M.

1986-01-01

A description is presented of the Cancer cluster of galaxies, based on a taxonomical analysis in (α,delta, Vsub(r)) space. Earlier results by previous authors on the lack of dynamical entity of the cluster are confirmed. The present analysis points out the existence of a binary structure in the most populated region of the complex. (author)

Time-dependent risks of cancer clustering among couples: a nationwide population-based cohort study in Taiwan.

Science.gov (United States)

Wang, Jong-Yi; Liang, Yia-Wen; Yeh, Chun-Chen; Liu, Chiu-Shong; Wang, Chen-Yu

2018-02-21

Spousal clustering of cancer warrants attention. Whether the common environment or high-age vulnerability determines cancer clustering is unclear. The risk of clustering in couples versus non-couples is undetermined. The time to cancer clustering after the first cancer diagnosis is yet to be reported. This study investigated cancer clustering over time among couples by using nationwide data. A cohort of 5643 married couples in the 2002-2013 Taiwan National Health Insurance Research Database was identified and randomly matched with 5643 non-couple pairs through dual propensity score matching. Factors associated with clustering (both spouses with tumours) were analysed by using the Cox proportional hazard model. Propensity-matched analysis revealed that the risk of clustering of all tumours among couples (13.70%) was significantly higher than that among non-couples (11.84%) (OR=1.182, 95% CI 1.058 to 1.321, P=0.0031). The median time to clustering of all tumours and of malignant tumours was 2.92 and 2.32 years, respectively. Risk characteristics associated with clustering included high age and comorbidity. Shared environmental factors among spouses might be linked to a high incidence of cancer clustering. Cancer incidence in one spouse may signal cancer vulnerability in the other spouse. Promoting family-oriented cancer care in vulnerable families and preventing shared lifestyle risk factors for cancer are suggested. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Modeling familial clustered breast cancer using published data

NARCIS (Netherlands)

Jonker, MA; Jacobi, CE; Hoogendoorn, WE; Nagelkerke, NJD; de Bock, GH; van Houwelingen, JC

2003-01-01

The purpose of this research was to model the familial clustering of breast cancer and to provide an accurate risk estimate for individuals from the general population, based on their family history of breast and ovarian cancer. We constructed a genetic model as an extension of a model by Claus et

Adenomatous polyposis coli (APC) regulates miR17-92 cluster through β-catenin pathway in colorectal cancer.

Science.gov (United States)

Li, Yajuan; Lauriola, Mattia; Kim, Donghwa; Francesconi, Mirko; D'Uva, Gabriele; Shibata, Dave; Malafa, Mokenge P; Yeatman, Timothy J; Coppola, Domenico; Solmi, Rossella; Cheng, Jin Q

2016-09-01

Adenomatous polyposis coli (APC) mutation is the most common genetic change in sporadic colorectal cancer (CRC). Although deregulations of miRNAs have been frequently reported in this malignancy, APC-regulated miRNAs have not been extensively documented. Here, by using an APC-inducible cell line and array analysis, we identified a total of 26 deregulated miRNAs. Among them, members of miR-17-92 cluster were dramatically inhibited by APC and induced by enforced expression of β-catenin. Furthermore, we demonstrate that activated β-catenin resulted from APC loss binds to and activates the miR-17-92 promoter. Notably, enforced expression of miR-19a overrides APC tumor suppressor activity, and knockdown of miR-19a in cancer cells with compromised APC function reduced their aggressive features in vitro. Finally, we observed that expression of miR-19a significantly correlates with β-catenin levels in colorectal cancer specimens, and it is associated to the aggressive stage of tumor progression. Thus, our study reveals that miR-17-92 cluster is directly regulated by APC/β-catenin pathway and could be a potential therapeutic target in colon cancers with aberrant APC/β-catenin signaling.

Non-negative matrix factorization by maximizing correntropy for cancer clustering

KAUST Repository

Wang, Jim Jing-Yan; Wang, Xiaolei; Gao, Xin

2013-01-01

Background: Non-negative matrix factorization (NMF) has been shown to be a powerful tool for clustering gene expression data, which are widely used to classify cancers. NMF aims to find two non-negative matrices whose product closely approximates the original matrix. Traditional NMF methods minimize either the l2 norm or the Kullback-Leibler distance between the product of the two matrices and the original matrix. Correntropy was recently shown to be an effective similarity measurement due to its stability to outliers or noise.Results: We propose a maximum correntropy criterion (MCC)-based NMF method (NMF-MCC) for gene expression data-based cancer clustering. Instead of minimizing the l2 norm or the Kullback-Leibler distance, NMF-MCC maximizes the correntropy between the product of the two matrices and the original matrix. The optimization problem can be solved by an expectation conditional maximization algorithm.Conclusions: Extensive experiments on six cancer benchmark sets demonstrate that the proposed method is significantly more accurate than the state-of-the-art methods in cancer clustering. 2013 Wang et al.; licensee BioMed Central Ltd.

Non-negative matrix factorization by maximizing correntropy for cancer clustering

KAUST Repository

Wang, Jim Jing-Yan

2013-03-24

Background: Non-negative matrix factorization (NMF) has been shown to be a powerful tool for clustering gene expression data, which are widely used to classify cancers. NMF aims to find two non-negative matrices whose product closely approximates the original matrix. Traditional NMF methods minimize either the l2 norm or the Kullback-Leibler distance between the product of the two matrices and the original matrix. Correntropy was recently shown to be an effective similarity measurement due to its stability to outliers or noise.Results: We propose a maximum correntropy criterion (MCC)-based NMF method (NMF-MCC) for gene expression data-based cancer clustering. Instead of minimizing the l2 norm or the Kullback-Leibler distance, NMF-MCC maximizes the correntropy between the product of the two matrices and the original matrix. The optimization problem can be solved by an expectation conditional maximization algorithm.Conclusions: Extensive experiments on six cancer benchmark sets demonstrate that the proposed method is significantly more accurate than the state-of-the-art methods in cancer clustering. 2013 Wang et al.; licensee BioMed Central Ltd.

Hierarchical clustering of breast cancer methylomes revealed differentially methylated and expressed breast cancer genes.

Directory of Open Access Journals (Sweden)

I-Hsuan Lin

Full Text Available Oncogenic transformation of normal cells often involves epigenetic alterations, including histone modification and DNA methylation. We conducted whole-genome bisulfite sequencing to determine the DNA methylomes of normal breast, fibroadenoma, invasive ductal carcinomas and MCF7. The emergence, disappearance, expansion and contraction of kilobase-sized hypomethylated regions (HMRs and the hypomethylation of the megabase-sized partially methylated domains (PMDs are the major forms of methylation changes observed in breast tumor samples. Hierarchical clustering of HMR revealed tumor-specific hypermethylated clusters and differential methylated enhancers specific to normal or breast cancer cell lines. Joint analysis of gene expression and DNA methylation data of normal breast and breast cancer cells identified differentially methylated and expressed genes associated with breast and/or ovarian cancers in cancer-specific HMR clusters. Furthermore, aberrant patterns of X-chromosome inactivation (XCI was found in breast cancer cell lines as well as breast tumor samples in the TCGA BRCA (breast invasive carcinoma dataset. They were characterized with differentially hypermethylated XIST promoter, reduced expression of XIST, and over-expression of hypomethylated X-linked genes. High expressions of these genes were significantly associated with lower survival rates in breast cancer patients. Comprehensive analysis of the normal and breast tumor methylomes suggests selective targeting of DNA methylation changes during breast cancer progression. The weak causal relationship between DNA methylation and gene expression observed in this study is evident of more complex role of DNA methylation in the regulation of gene expression in human epigenetics that deserves further investigation.

Myeloid clusters are associated with a pro-metastatic environment and poor prognosis in smoking-related early stage non-small cell lung cancer.

Directory of Open Access Journals (Sweden)

Wang Zhang

Full Text Available This study aimed to understand the role of myeloid cell clusters in uninvolved regional lymph nodes from early stage non-small cell lung cancer patients.Uninvolved regional lymph node sections from 67 patients with stage I-III resected non-small cell lung cancer were immunostained to detect myeloid clusters, STAT3 activity and occult metastasis. Anthracosis intensity, myeloid cluster infiltration associated with anthracosis and pSTAT3 level were scored and correlated with patient survival. Multivariate Cox regression analysis was performed with prognostic variables. Human macrophages were used for in vitro nicotine treatment.CD68+ myeloid clusters associated with anthracosis and with an immunosuppressive and metastasis-promoting phenotype and elevated overall STAT3 activity were observed in uninvolved lymph nodes. In patients with a smoking history, myeloid cluster score significantly correlated with anthracosis intensity and pSTAT3 level (P<0.01. Nicotine activated STAT3 in macrophages in long-term culture. CD68+ myeloid clusters correlated and colocalized with occult metastasis. Myeloid cluster score was an independent prognostic factor (P = 0.049 and was associated with survival by Kaplan-Maier estimate in patients with a history of smoking (P = 0.055. The combination of myeloid cluster score with either lymph node stage or pSTAT3 level defined two populations with a significant difference in survival (P = 0.024 and P = 0.004, respectively.Myeloid clusters facilitate a pro-metastatic microenvironment in uninvolved regional lymph nodes and associate with occult metastasis in early stage non-small cell lung cancer. Myeloid cluster score is an independent prognostic factor for survival in patients with a history of smoking, and may present a novel method to inform therapy choices in the adjuvant setting. Further validation studies are warranted.

Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells

Directory of Open Access Journals (Sweden)

Wernet Peter

2010-08-01

Full Text Available Abstract Background The miR-200c/141 cluster has recently been implicated in the epithelial to mesenchymal transition (EMT process. The expression of these two miRNAs is inversely correlated with tumorigenicity and invasiveness in several human cancers. The role of these miRNAs in cancer progression is based in part on their capacity to target the EMT activators ZEB1 and ZEB2, two transcription factors, which in turn repress expression of E-cadherin. Little is known about the regulation of the mir200c/141 cluster, whose targeting has been proposed as a promising new therapy for the most aggressive tumors. Findings We show that the miR-200c/141 cluster is repressed by DNA methylation of a CpG island located in the promoter region of these miRNAs. Whereas in vitro methylation of the miR-200c/141 promoter led to shutdown of promoter activity, treatment with a demethylating agent caused transcriptional reactivation in breast cancer cells formerly lacking expression of miR-200c and miR-141. More importantly, we observed that DNA methylation of the identified miR-200c/141 promoter was tightly correlated with phenotype and the invasive capacity in a panel of 8 human breast cancer cell lines. In line with this, in vitro induction of EMT by ectopic expression of the EMT transcription factor Twist in human immortalized mammary epithelial cells (HMLE was accompanied by increased DNA methylation and concomitant repression of the miR-200c/141 locus. Conclusions The present study demonstrates that expression of the miR-200c/141 cluster is regulated by DNA methylation, suggesting epigenetic regulation of this miRNA locus in aggressive breast cancer cell lines as well as untransformed mammary epithelial cells. This epigenetic silencing mechanism might represent a novel component of the regulatory circuit for the maintenance of EMT programs in cancer and normal cells.

Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells.

Science.gov (United States)

Neves, Rui; Scheel, Christina; Weinhold, Sandra; Honisch, Ellen; Iwaniuk, Katharina M; Trompeter, Hans-Ingo; Niederacher, Dieter; Wernet, Peter; Santourlidis, Simeon; Uhrberg, Markus

2010-08-03

The miR-200c/141 cluster has recently been implicated in the epithelial to mesenchymal transition (EMT) process. The expression of these two miRNAs is inversely correlated with tumorigenicity and invasiveness in several human cancers. The role of these miRNAs in cancer progression is based in part on their capacity to target the EMT activators ZEB1 and ZEB2, two transcription factors, which in turn repress expression of E-cadherin. Little is known about the regulation of the mir200c/141 cluster, whose targeting has been proposed as a promising new therapy for the most aggressive tumors. We show that the miR-200c/141 cluster is repressed by DNA methylation of a CpG island located in the promoter region of these miRNAs. Whereas in vitro methylation of the miR-200c/141 promoter led to shutdown of promoter activity, treatment with a demethylating agent caused transcriptional reactivation in breast cancer cells formerly lacking expression of miR-200c and miR-141. More importantly, we observed that DNA methylation of the identified miR-200c/141 promoter was tightly correlated with phenotype and the invasive capacity in a panel of 8 human breast cancer cell lines. In line with this, in vitro induction of EMT by ectopic expression of the EMT transcription factor Twist in human immortalized mammary epithelial cells (HMLE) was accompanied by increased DNA methylation and concomitant repression of the miR-200c/141 locus. The present study demonstrates that expression of the miR-200c/141 cluster is regulated by DNA methylation, suggesting epigenetic regulation of this miRNA locus in aggressive breast cancer cell lines as well as untransformed mammary epithelial cells. This epigenetic silencing mechanism might represent a novel component of the regulatory circuit for the maintenance of EMT programs in cancer and normal cells.

Symptom Clusters in Advanced Cancer Patients: An Empirical Comparison of Statistical Methods and the Impact on Quality of Life.

Science.gov (United States)

Dong, Skye T; Costa, Daniel S J; Butow, Phyllis N; Lovell, Melanie R; Agar, Meera; Velikova, Galina; Teckle, Paulos; Tong, Allison; Tebbutt, Niall C; Clarke, Stephen J; van der Hoek, Kim; King, Madeleine T; Fayers, Peter M

2016-01-01

Symptom clusters in advanced cancer can influence patient outcomes. There is large heterogeneity in the methods used to identify symptom clusters. To investigate the consistency of symptom cluster composition in advanced cancer patients using different statistical methodologies for all patients across five primary cancer sites, and to examine which clusters predict functional status, a global assessment of health and global quality of life. Principal component analysis and exploratory factor analysis (with different rotation and factor selection methods) and hierarchical cluster analysis (with different linkage and similarity measures) were used on a data set of 1562 advanced cancer patients who completed the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Four clusters consistently formed for many of the methods and cancer sites: tense-worry-irritable-depressed (emotional cluster), fatigue-pain, nausea-vomiting, and concentration-memory (cognitive cluster). The emotional cluster was a stronger predictor of overall quality of life than the other clusters. Fatigue-pain was a stronger predictor of overall health than the other clusters. The cognitive cluster and fatigue-pain predicted physical functioning, role functioning, and social functioning. The four identified symptom clusters were consistent across statistical methods and cancer types, although there were some noteworthy differences. Statistical derivation of symptom clusters is in need of greater methodological guidance. A psychosocial pathway in the management of symptom clusters may improve quality of life. Biological mechanisms underpinning symptom clusters need to be delineated by future research. A framework for evidence-based screening, assessment, treatment, and follow-up of symptom clusters in advanced cancer is essential. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

1842676957299765Latent class cluster analysis to understand heterogeneity in prostate cancer treatment utilities

Directory of Open Access Journals (Sweden)

Meghani Salimah

2009-01-01

Full Text Available Abstract Background Men with prostate cancer are often challenged to choose between conservative management and a range of available treatment options each carrying varying risks and benefits. The trade-offs are between an improved life-expectancy with treatment accompanied by important risks such as urinary incontinence and erectile dysfunction. Previous studies of preference elicitation for prostate cancer treatment have found considerable heterogeneity in individuals' preferences for health states given similar treatments and clinical risks. Methods Using latent class mixture model (LCA, we first sought to understand if there are unique patterns of heterogeneity or subgroups of individuals based on their prostate cancer treatment utilities (calculated time trade-off utilities for various health states and if such unique subgroups exist, what demographic and urological variables may predict membership in these subgroups. Results The sample (N = 244 included men with prostate cancer (n = 188 and men at-risk for disease (n = 56. The sample was predominantly white (77%, with mean age of 60 years (SD ± 9.5. Most (85.9% were married or living with a significant other. Using LCA, a three class solution yielded the best model evidenced by the smallest Bayesian Information Criterion (BIC, substantial reduction in BIC from a 2-class solution, and Lo-Mendell-Rubin significance of < .001. The three identified clusters were named high-traders (n = 31, low-traders (n = 116, and no-traders (n = 97. High-traders were more likely to trade survival time associated with treatment to avoid potential risks of treatment. Low-traders were less likely to trade survival time and accepted risks of treatment. The no-traders were likely to make no trade-offs in any direction favouring the status quo. There was significant difference among the clusters in the importance of sexual activity (Pearson's χ2 = 16.55, P = 0.002; Goodman and Kruskal tau = 0.039, P < 0.001. In

Nemosis, a novel way of fibroblast activation, in inflammation and cancer

Energy Technology Data Exchange (ETDEWEB)

Vaheri, Antti, E-mail: antti.vaheri@helsinki.fi [Haartman Institute, POB 21, FI-00014 University of Helsinki (Finland); Enzerink, Anna; Raesaenen, Kati; Salmenperae, Pertteli [Haartman Institute, POB 21, FI-00014 University of Helsinki (Finland)

2009-06-10

Malignant cells when grown in suspension, as a rule, proliferate and can form spheroids that have been used as a model of tumor nodules, micrometastases and avascular tumors. In contrast, normal adherent cells cannot be stimulated to grow as multicellular aggregates. Now, recent results show that normal fibroblasts if forced to cluster (spheroid formation) do not grow but undergo a new pathway of cell activation (nemosis) leading to a massive proinflammatory, proteolytic and growth factor response. The clustering and activation are initiated by fibronectin-integrin interaction. The activated fibroblasts are able to modulate the behavior of cancer cells and, furthermore malignant cells boost this activation even further. In this model, the activation of fibroblasts terminates in programmed necrosis-like cell death. Activation of the tumor stroma, especially of fibroblasts, is of critical importance for tumor progression, although mechanisms leading to their activation are still largely uncharacterized. In summary, our results suggest that this kind of fibroblast activation (nemosis) may be involved in pathological conditions such as inflammation and cancer.

Nemosis, a novel way of fibroblast activation, in inflammation and cancer

International Nuclear Information System (INIS)

Vaheri, Antti; Enzerink, Anna; Raesaenen, Kati; Salmenperae, Pertteli

2009-01-01

Malignant cells when grown in suspension, as a rule, proliferate and can form spheroids that have been used as a model of tumor nodules, micrometastases and avascular tumors. In contrast, normal adherent cells cannot be stimulated to grow as multicellular aggregates. Now, recent results show that normal fibroblasts if forced to cluster (spheroid formation) do not grow but undergo a new pathway of cell activation (nemosis) leading to a massive proinflammatory, proteolytic and growth factor response. The clustering and activation are initiated by fibronectin-integrin interaction. The activated fibroblasts are able to modulate the behavior of cancer cells and, furthermore malignant cells boost this activation even further. In this model, the activation of fibroblasts terminates in programmed necrosis-like cell death. Activation of the tumor stroma, especially of fibroblasts, is of critical importance for tumor progression, although mechanisms leading to their activation are still largely uncharacterized. In summary, our results suggest that this kind of fibroblast activation (nemosis) may be involved in pathological conditions such as inflammation and cancer.

Re-estimating sample size in cluster randomized trials with active recruitment within clusters

NARCIS (Netherlands)

van Schie, Sander; Moerbeek, Mirjam

2014-01-01

Often only a limited number of clusters can be obtained in cluster randomised trials, although many potential participants can be recruited within each cluster. Thus, active recruitment is feasible within the clusters. To obtain an efficient sample size in a cluster randomised trial, the cluster

Cluster symptoms in cancer patients: A systematic Review

OpenAIRE

Anastasios Tzenalis; Ioanna Vekili

2013-01-01

Clinical studies have shown that patients with cancer experience multiple and simultaneously occurring symptoms, both during the illness and the therapeutic interventions. Aim: The aim of the present systematic review study was to investigate the symptom complex (cluster symptoms) occurring in patients suffering from cancer and their effect on the outcome of the disease. Methods: Data collection was based on electronic databases «MEDLINE / PubMed», «CINAHL», «PsycINFO», «Science Direct», «Spr...

Effects of symptom clusters and depression on the quality of life in patients with advanced lung cancer.

Science.gov (United States)

Choi, S; Ryu, E

2018-01-01

People with advanced lung cancer experience later symptoms after treatment that is related to poorer psychosocial and quality of life (QOL) outcomes. The purpose of this study was to identify the effect of symptom clusters and depression on the QOL of patients with advanced lung cancer. A sample of 178 patients with advanced lung cancer at the National Cancer Center in Korea completed a demographic questionnaire, the M.D. Anderson Symptom Inventory-Lung Cancer, the Center for Epidemiological Studies Depression Scale, and the Functional Assessment of Cancer Therapy-General scale. The most frequently experienced symptom was fatigue, anguish was the most severe symptom-associated distress, and 28.9% of participants were clinically depressed. Factor analysis was used to identify symptom clusters based on the severity of patients' symptom experiences. Three symptom clusters were identified: treatment-associated, lung cancer and psychological symptom clusters. The regression model found a significant negative impact on QOL for depression and lung cancer symptom cluster. Age as the control variable was found to be significant impact on QOL. Therefore, psychological screening and appropriate intervention is an essential part of advanced cancer care. Both pharmacological and non-pharmacological approaches for alleviating depression may help to improve the QOL of lung cancer patients. © 2016 John Wiley & Sons Ltd.

Symptom clusters and related factors in bladder cancer patients three months after radical cystectomy.

Science.gov (United States)

Ren, Hongyan; Tang, Ping; Zhao, Qinghua; Ren, Guosheng

2017-08-23

To identify symptom distress and clusters in patients 3 months after radical cystectomy and to explore their potential predictors. A cross-sectional design was used to investigate 99 bladder cancer patients 3 months after radical cystectomy. Data were collected by demographic and disease characteristic questionnaires, the symptom experience scale of the M.D. Anderson symptom inventory, two additional symptoms specific to radical cystectomy, and the functional assessment of cancer therapy questionnaire. A factor analysis, stepwise regression, and correlation analysis were applied. Three symptom clusters were identified: fatigue-malaise, gastrointestinal, and psycho-urinary. Age, complication severity, albumin post-surgery (negative), orthotropic neobladder reconstruction, adjuvant chemotherapy and American Society of Anesthesiologists (ASA) scores were significant predictors of fatigue-malaise. Adjuvant chemotherapy, orthotropic neobladder reconstruction, female gender, ASA scores and albumin (negative) were significant predictors of gastrointestinal symptoms. Being unmarried, having a higher educational level and complication severity were significant predictors of psycho-urinary symptoms. The correlations between clusters and for each cluster with quality of life were significant, with the highest correlation observed between the psycho-urinary cluster and quality of life. Bladder cancer patients experience concurrent symptoms that appear to cluster and are significantly correlated with quality of life. Moreover, symptom clusters may be predicted by certain demographic and clinical characteristics.

Downregulation of miR-130b~301b cluster is mediated by aberrant promoter methylation and impairs cellular senescence in prostate cancer

Directory of Open Access Journals (Sweden)

João Ramalho-Carvalho

2017-02-01

Full Text Available Abstract Background Numerous DNA-damaging cellular stresses, including oncogene activation and DNA-damage response (DDR, may lead to cellular senescence. Previous observations linked microRNA deregulation with altered senescent patterns, prompting us to investigate whether epigenetic repression of microRNAs expression might disrupt senescence in prostate cancer (PCa cells. Methods Differential methylation mapping in prostate tissues was carried using Infinium HumanMethylation450 BeadChip. After validation of methylation and expression analyses in a larger series of prostate tissues, the functional role of the cluster miR-130b~301b was explored using in vitro studies testing cell viability, apoptosis, invasion and DNA damage in prostate cancer cell lines. Western blot and RT-qPCR were performed to support those observations. Results We found that the miR-130b~301b cluster directs epigenetic activation of cell cycle inhibitors required for DDR activation, thus stimulating the senescence-associated secretory phenotype (SASP. Furthermore, overexpression of miR-130b~301b cluster markedly reduced the malignant phenotype of PCa cells. Conclusions Altogether, these data demonstrate that miR-130b~301b cluster overexpression might effectively induce PCa cell growth arrest through epigenetic regulation of proliferation-blocking genes and activation of cellular senescence.

DEMARCATE: Density-based magnetic resonance image clustering for assessing tumor heterogeneity in cancer.

Science.gov (United States)

Saha, Abhijoy; Banerjee, Sayantan; Kurtek, Sebastian; Narang, Shivali; Lee, Joonsang; Rao, Ganesh; Martinez, Juan; Bharath, Karthik; Rao, Arvind U K; Baladandayuthapani, Veerabhadran

2016-01-01

Tumor heterogeneity is a crucial area of cancer research wherein inter- and intra-tumor differences are investigated to assess and monitor disease development and progression, especially in cancer. The proliferation of imaging and linked genomic data has enabled us to evaluate tumor heterogeneity on multiple levels. In this work, we examine magnetic resonance imaging (MRI) in patients with brain cancer to assess image-based tumor heterogeneity. Standard approaches to this problem use scalar summary measures (e.g., intensity-based histogram statistics) that do not adequately capture the complete and finer scale information in the voxel-level data. In this paper, we introduce a novel technique, DEMARCATE (DEnsity-based MAgnetic Resonance image Clustering for Assessing Tumor hEterogeneity) to explore the entire tumor heterogeneity density profiles (THDPs) obtained from the full tumor voxel space. THDPs are smoothed representations of the probability density function of the tumor images. We develop tools for analyzing such objects under the Fisher-Rao Riemannian framework that allows us to construct metrics for THDP comparisons across patients, which can be used in conjunction with standard clustering approaches. Our analyses of The Cancer Genome Atlas (TCGA) based Glioblastoma dataset reveal two significant clusters of patients with marked differences in tumor morphology, genomic characteristics and prognostic clinical outcomes. In addition, we see enrichment of image-based clusters with known molecular subtypes of glioblastoma multiforme, which further validates our representation of tumor heterogeneity and subsequent clustering techniques.

Trajectories of Symptom Clusters, Performance Status, and Quality of Life During Concurrent Chemoradiotherapy in Patients With High-Grade Brain Cancers.

Science.gov (United States)

Kim, Sang-Hee; Byun, Youngsoon

Symptom clusters must be identified in patients with high-grade brain cancers for effective symptom management during cancer-related therapy. The aims of this study were to identify symptom clusters in patients with high-grade brain cancers and to determine the relationship of each cluster with the performance status and quality of life (QOL) during concurrent chemoradiotherapy (CCRT). Symptoms were assessed using the Memorial Symptom Assessment Scale, and the performance status was evaluated using the Karnofsky Performance Scale. Quality of life was assessed using the Functional Assessment of Cancer Therapy-General. This prospective longitudinal survey was conducted before CCRT and at 2 to 3 weeks and 4 to 6 weeks after the initiation of CCRT. A total of 51 patients with newly diagnosed primary malignant brain cancer were included. Six symptom clusters were identified, and 2 symptom clusters were present at each time point (ie, "negative emotion" and "neurocognitive" clusters before CCRT, "negative emotion and decreased vitality" and "gastrointestinal and decreased sensory" clusters at 2-3 weeks, and "body image and decreased vitality" and "gastrointestinal" clusters at 4-6 weeks). The symptom clusters at each time point demonstrated a significant relationship with the performance status or QOL. Differences were observed in symptom clusters in patients with high-grade brain cancers during CCRT. In addition, the symptom clusters were correlated with the performance status and QOL of patients, and these effects could change during CCRT. The results of this study will provide suggestions for interventions to treat or prevent symptom clusters in patients with high-grade brain cancer during CCRT.

MicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU.

Directory of Open Access Journals (Sweden)

Elena Favaro

2010-04-01

Full Text Available Hypoxia in cancers results in the upregulation of hypoxia inducible factor 1 (HIF-1 and a microRNA, hsa-miR-210 (miR-210 which is associated with a poor prognosis.In human cancer cell lines and tumours, we found that miR-210 targets the mitochondrial iron sulfur scaffold protein ISCU, required for assembly of iron-sulfur clusters, cofactors for key enzymes involved in the Krebs cycle, electron transport, and iron metabolism. Down regulation of ISCU was the major cause of induction of reactive oxygen species (ROS in hypoxia. ISCU suppression reduced mitochondrial complex 1 activity and aconitase activity, caused a shift to glycolysis in normoxia and enhanced cell survival. Cancers with low ISCU had a worse prognosis.Induction of these major hallmarks of cancer show that a single microRNA, miR-210, mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation.

A Cluster- Based Secure Active Network Environment

Institute of Scientific and Technical Information of China (English)

CHEN Xiao-lin; ZHOU Jing-yang; DAI Han; LU Sang-lu; CHEN Gui-hai

2005-01-01

We introduce a cluster-based secure active network environment (CSANE) which separates the processing of IP packets from that of active packets in active routers. In this environment, the active code authorized or trusted by privileged users is executed in the secure execution environment (EE) of the active router, while others are executed in the secure EE of the nodes in the distributed shared memory (DSM) cluster. With the supports of a multi-process Java virtual machine and KeyNote, untrusted active packets are controlled to securely consume resource. The DSM consistency management makes that active packets can be parallelly processed in the DSM cluster as if they were processed one by one in ANTS (Active Network Transport System). We demonstrate that CSANE has good security and scalability, but imposing little changes on traditional routers.

Space-Time Analysis of Testicular Cancer Clusters Using Residential Histories: A Case-Control Study in Denmark

Science.gov (United States)

Sloan, Chantel D.; Nordsborg, Rikke B.; Jacquez, Geoffrey M.; Raaschou-Nielsen, Ole; Meliker, Jaymie R.

2015-01-01

Though the etiology is largely unknown, testicular cancer incidence has seen recent significant increases in northern Europe and throughout many Western regions. The most common cancer in males under age 40, age period cohort models have posited exposures in the in utero environment or in early childhood as possible causes of increased risk of testicular cancer. Some of these factors may be tied to geography through being associated with behavioral, cultural, sociodemographic or built environment characteristics. If so, this could result in detectable geographic clusters of cases that could lead to hypotheses regarding environmental targets for intervention. Given a latency period between exposure to an environmental carcinogen and testicular cancer diagnosis, mobility histories are beneficial for spatial cluster analyses. Nearest-neighbor based Q-statistics allow for the incorporation of changes in residency in spatial disease cluster detection. Using these methods, a space-time cluster analysis was conducted on a population-wide case-control population selected from the Danish Cancer Registry with mobility histories since 1971 extracted from the Danish Civil Registration System. Cases (N=3297) were diagnosed between 1991 and 2003, and two sets of controls (N=3297 for each set) matched on sex and date of birth were included in the study. We also examined spatial patterns in maternal residential history for those cases and controls born in 1971 or later (N= 589 case-control pairs). Several small clusters were detected when aligning individuals by year prior to diagnosis, age at diagnosis and calendar year of diagnosis. However, the largest of these clusters contained only 2 statistically significant individuals at their center, and were not replicated in SaTScan spatial-only analyses which are less susceptible to multiple testing bias. We found little evidence of local clusters in residential histories of testicular cancer cases in this Danish population. PMID

Space-time analysis of testicular cancer clusters using residential histories: a case-control study in Denmark.

Directory of Open Access Journals (Sweden)

Chantel D Sloan

Full Text Available Though the etiology is largely unknown, testicular cancer incidence has seen recent significant increases in northern Europe and throughout many Western regions. The most common cancer in males under age 40, age period cohort models have posited exposures in the in utero environment or in early childhood as possible causes of increased risk of testicular cancer. Some of these factors may be tied to geography through being associated with behavioral, cultural, sociodemographic or built environment characteristics. If so, this could result in detectable geographic clusters of cases that could lead to hypotheses regarding environmental targets for intervention. Given a latency period between exposure to an environmental carcinogen and testicular cancer diagnosis, mobility histories are beneficial for spatial cluster analyses. Nearest-neighbor based Q-statistics allow for the incorporation of changes in residency in spatial disease cluster detection. Using these methods, a space-time cluster analysis was conducted on a population-wide case-control population selected from the Danish Cancer Registry with mobility histories since 1971 extracted from the Danish Civil Registration System. Cases (N=3297 were diagnosed between 1991 and 2003, and two sets of controls (N=3297 for each set matched on sex and date of birth were included in the study. We also examined spatial patterns in maternal residential history for those cases and controls born in 1971 or later (N= 589 case-control pairs. Several small clusters were detected when aligning individuals by year prior to diagnosis, age at diagnosis and calendar year of diagnosis. However, the largest of these clusters contained only 2 statistically significant individuals at their center, and were not replicated in SaTScan spatial-only analyses which are less susceptible to multiple testing bias. We found little evidence of local clusters in residential histories of testicular cancer cases in this Danish

Space-time analysis of testicular cancer clusters using residential histories: a case-control study in Denmark.

Science.gov (United States)

Sloan, Chantel D; Nordsborg, Rikke B; Jacquez, Geoffrey M; Raaschou-Nielsen, Ole; Meliker, Jaymie R

2015-01-01

Though the etiology is largely unknown, testicular cancer incidence has seen recent significant increases in northern Europe and throughout many Western regions. The most common cancer in males under age 40, age period cohort models have posited exposures in the in utero environment or in early childhood as possible causes of increased risk of testicular cancer. Some of these factors may be tied to geography through being associated with behavioral, cultural, sociodemographic or built environment characteristics. If so, this could result in detectable geographic clusters of cases that could lead to hypotheses regarding environmental targets for intervention. Given a latency period between exposure to an environmental carcinogen and testicular cancer diagnosis, mobility histories are beneficial for spatial cluster analyses. Nearest-neighbor based Q-statistics allow for the incorporation of changes in residency in spatial disease cluster detection. Using these methods, a space-time cluster analysis was conducted on a population-wide case-control population selected from the Danish Cancer Registry with mobility histories since 1971 extracted from the Danish Civil Registration System. Cases (N=3297) were diagnosed between 1991 and 2003, and two sets of controls (N=3297 for each set) matched on sex and date of birth were included in the study. We also examined spatial patterns in maternal residential history for those cases and controls born in 1971 or later (N= 589 case-control pairs). Several small clusters were detected when aligning individuals by year prior to diagnosis, age at diagnosis and calendar year of diagnosis. However, the largest of these clusters contained only 2 statistically significant individuals at their center, and were not replicated in SaTScan spatial-only analyses which are less susceptible to multiple testing bias. We found little evidence of local clusters in residential histories of testicular cancer cases in this Danish population.

Role of DNA methylation in miR-200c/141 cluster silencing in invasive breast cancer cells

OpenAIRE

Neves, Rui; Scheel, Christina; Weinhold, Sandra; Honisch, Ellen; Iwaniuk, Katharina M; Trompeter, Hans-Ingo; Niederacher, Dieter; Wernet, Peter; Santourlidis, Simeon; Uhrberg, Markus

2010-01-01

Abstract Background The miR-200c/141 cluster has recently been implicated in the epithelial to mesenchymal transition (EMT) process. The expression of these two miRNAs is inversely correlated with tumorigenicity and invasiveness in several human cancers. The role of these miRNAs in cancer progression is based in part on their capacity to target the EMT activators ZEB1 and ZEB2, two transcription factors, which in turn repress expression of E-cadherin. Little is known about the regulation of t...

Breast-related stereotype threat contributes to a symptom cluster in women with breast cancer.

Science.gov (United States)

Li, Jie; Gao, Wei; Yu, Li-Xiang; Zhu, Song-Ying; Cao, Feng-Lin

2017-05-01

To investigate the prevalence of breast-related stereotype threat and its effects on a symptom cluster consisting of anxiety, depression and fatigue and on each symptom. The stereotype that breasts are a sign of women's femininity results in patients with breast cancer fearing diminished femininity and rejection, which may induce psychological problems that co-occur as a symptom cluster. Cross-sectional study. A total of 131 patients with breast cancer postmastectomy completed the study. A question measuring breast-related stereotype threat, the Hospital Anxiety and Depression Scale and the Functional Assessment of Chronic Illness Therapy-Fatigue Scale were used to assess their breast-related stereotype threat and symptoms of anxiety, depression and fatigue. Of the 131 patients who answered the breast-related stereotype threat question, 86 (65·6%) reported breast-related stereotype threat. They did not differ significantly in social and clinical characteristics compared with those without the stereotype, but did report significantly higher levels of the symptom cluster and each symptom (anxiety, depression and fatigue). The odds ratios of the stereotype were significant for the symptom cluster, depression and fatigue (odds ratios = 2·52-3·98, p stereotype threat was common in patients with breast cancer. There was about a twofold increase in their risk of experiencing the symptom cluster and symptoms of depression and fatigue. In clinical practice, breast-related stereotype threat should be measured together with prevalent symptoms (e.g. anxiety, depression and fatigue) in patients with breast cancer. Our findings will aid the development of interventions for improving the mental health of women with breast cancer. © 2016 John Wiley & Sons Ltd.

Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers.

Science.gov (United States)

Murlidhar, Vasudha; Reddy, Rishindra M; Fouladdel, Shamileh; Zhao, Lili; Ishikawa, Martin K; Grabauskiene, Svetlana; Zhang, Zhuo; Lin, Jules; Chang, Andrew C; Carrott, Philip; Lynch, William R; Orringer, Mark B; Kumar-Sinha, Chandan; Palanisamy, Nallasivam; Beer, David G; Wicha, Max S; Ramnath, Nithya; Azizi, Ebrahim; Nagrath, Sunitha

2017-09-15

Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe ( P ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194-206. ©2017 AACR . ©2017 American Association for Cancer Research.

Adolescent Cancer Education (ACE) to increase adolescent and parent cancer awareness and communication: study protocol for a cluster randomised controlled trial.

Science.gov (United States)

Kyle, Richard G; Macmillan, Iona; Rauchhaus, Petra; O'Carroll, Ronan; Neal, Richard D; Forbat, Liz; Haw, Sally; Hubbard, Gill

2013-09-08

multiple regression methods, adjusted for clustering by school. An audit of cancer-related and health-promotion activity within the school curriculum and environment during the RCT will be conducted at six-month follow-up to contextualise the intervention effect. Results from the ACE study will provide evidence about the public health effectiveness of a school-based intervention designed to increase adolescent and parent cancer awareness and adolescent-parent cancer communication. ISRCTN75542411.

An enhanced deterministic K-Means clustering algorithm for cancer subtype prediction from gene expression data.

Science.gov (United States)

Nidheesh, N; Abdul Nazeer, K A; Ameer, P M

2017-12-01

Clustering algorithms with steps involving randomness usually give different results on different executions for the same dataset. This non-deterministic nature of algorithms such as the K-Means clustering algorithm limits their applicability in areas such as cancer subtype prediction using gene expression data. It is hard to sensibly compare the results of such algorithms with those of other algorithms. The non-deterministic nature of K-Means is due to its random selection of data points as initial centroids. We propose an improved, density based version of K-Means, which involves a novel and systematic method for selecting initial centroids. The key idea of the algorithm is to select data points which belong to dense regions and which are adequately separated in feature space as the initial centroids. We compared the proposed algorithm to a set of eleven widely used single clustering algorithms and a prominent ensemble clustering algorithm which is being used for cancer data classification, based on the performances on a set of datasets comprising ten cancer gene expression datasets. The proposed algorithm has shown better overall performance than the others. There is a pressing need in the Biomedical domain for simple, easy-to-use and more accurate Machine Learning tools for cancer subtype prediction. The proposed algorithm is simple, easy-to-use and gives stable results. Moreover, it provides comparatively better predictions of cancer subtypes from gene expression data. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analysis of k-means clustering approach on the breast cancer Wisconsin dataset.

Science.gov (United States)

Dubey, Ashutosh Kumar; Gupta, Umesh; Jain, Sonal

2016-11-01

Breast cancer is one of the most common cancers found worldwide and most frequently found in women. An early detection of breast cancer provides the possibility of its cure; therefore, a large number of studies are currently going on to identify methods that can detect breast cancer in its early stages. This study was aimed to find the effects of k-means clustering algorithm with different computation measures like centroid, distance, split method, epoch, attribute, and iteration and to carefully consider and identify the combination of measures that has potential of highly accurate clustering accuracy. K-means algorithm was used to evaluate the impact of clustering using centroid initialization, distance measures, and split methods. The experiments were performed using breast cancer Wisconsin (BCW) diagnostic dataset. Foggy and random centroids were used for the centroid initialization. In foggy centroid, based on random values, the first centroid was calculated. For random centroid, the initial centroid was considered as (0, 0). The results were obtained by employing k-means algorithm and are discussed with different cases considering variable parameters. The calculations were based on the centroid (foggy/random), distance (Euclidean/Manhattan/Pearson), split (simple/variance), threshold (constant epoch/same centroid), attribute (2-9), and iteration (4-10). Approximately, 92 % average positive prediction accuracy was obtained with this approach. Better results were found for the same centroid and the highest variance. The results achieved using Euclidean and Manhattan were better than the Pearson correlation. The findings of this work provided extensive understanding of the computational parameters that can be used with k-means. The results indicated that k-means has a potential to classify BCW dataset.

Clusters - Tourism Activity Increase Competitiveness Support

Directory of Open Access Journals (Sweden)

Carmen IORDACHE

2010-05-01

Full Text Available Tourism represents one of those areas with the greatest potential of global expansion. Tourism development strategy in terms of maximizing its positive effects on regional economic increase and implicitly on the national one starts from the premise that in global economy value is created in regions which are defined as particular geographical entities, separated by geographical reasons and not as political-administrative structures, and economic increase is centrally cumulated and valued according to the economic policy and the national legal system.Regional economic system approach based on “cluster” concept is explained by the fact that the regional activities portfolio is based on an inter and intra-industry networking grouped by cluster, in which is created the value that increases as the activity results are leading to the final consumers.This type of communication aims to highlight the tourism role as a factor in regional development, the clustering process significance in obtaining some competitiveness advantages, clusters development in tourism beginnings, and also the identification methodology used to select one touristic area to create the cluster.

Chemisorption on size-selected metal clusters: activation barriers and chemical reactions for deuterium and aluminum cluster ions

International Nuclear Information System (INIS)

Jarrold, M.F.; Bower, J.E.

1988-01-01

The authors describe a new approach to investigating chemisorption on size-selected metal clusters. This approach involves investigating the collision-energy dependence of chemisorption using low-energy ion beam techniques. The method provides a direct measure of the activation barrier for chemisorption and in some cases an estimate of the desorption energy as well. They describe the application of this technique to chemisorption of deuterium on size-selected aluminum clusters. The activation barriers increase with cluster size (from a little over 1 eV for Al 10 + to around 2 eV for Al 27 + ) and show significant odd-even oscillations. The activation barriers for the clusters with an odd number of atoms are larger than those for the even-numbered clusters. In addition to chemisorption of deuterium onto the clusters, chemical reactions were observed, often resulting in cluster fragmentation. The main products observed were Al/sub n-1/D + , Al/sub n-2/ + , and Al + for clusters with n + and Al/sub n-1/D + for the larger clusters

Lung Cancer Signature Biomarkers: tissue specific semantic similarity based clustering of Digital Differential Display (DDD data

Directory of Open Access Journals (Sweden)

Srivastava Mousami

2012-11-01

Full Text Available Abstract Background The tissue-specific Unigene Sets derived from more than one million expressed sequence tags (ESTs in the NCBI, GenBank database offers a platform for identifying significantly and differentially expressed tissue-specific genes by in-silico methods. Digital differential display (DDD rapidly creates transcription profiles based on EST comparisons and numerically calculates, as a fraction of the pool of ESTs, the relative sequence abundance of known and novel genes. However, the process of identifying the most likely tissue for a specific disease in which to search for candidate genes from the pool of differentially expressed genes remains difficult. Therefore, we have used ‘Gene Ontology semantic similarity score’ to measure the GO similarity between gene products of lung tissue-specific candidate genes from control (normal and disease (cancer sets. This semantic similarity score matrix based on hierarchical clustering represents in the form of a dendrogram. The dendrogram cluster stability was assessed by multiple bootstrapping. Multiple bootstrapping also computes a p-value for each cluster and corrects the bias of the bootstrap probability. Results Subsequent hierarchical clustering by the multiple bootstrapping method (α = 0.95 identified seven clusters. The comparative, as well as subtractive, approach revealed a set of 38 biomarkers comprising four distinct lung cancer signature biomarker clusters (panel 1–4. Further gene enrichment analysis of the four panels revealed that each panel represents a set of lung cancer linked metastasis diagnostic biomarkers (panel 1, chemotherapy/drug resistance biomarkers (panel 2, hypoxia regulated biomarkers (panel 3 and lung extra cellular matrix biomarkers (panel 4. Conclusions Expression analysis reveals that hypoxia induced lung cancer related biomarkers (panel 3, HIF and its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1, SRC-1, FN1, APLP2, DMBT1

Exploring the individual patterns of spiritual well-being in people newly diagnosed with advanced cancer: a cluster analysis.

Science.gov (United States)

Bai, Mei; Dixon, Jane; Williams, Anna-Leila; Jeon, Sangchoon; Lazenby, Mark; McCorkle, Ruth

2016-11-01

Research shows that spiritual well-being correlates positively with quality of life (QOL) for people with cancer, whereas contradictory findings are frequently reported with respect to the differentiated associations between dimensions of spiritual well-being, namely peace, meaning and faith, and QOL. This study aimed to examine individual patterns of spiritual well-being among patients newly diagnosed with advanced cancer. Cluster analysis was based on the twelve items of the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale at Time 1. A combination of hierarchical and k-means (non-hierarchical) clustering methods was employed to jointly determine the number of clusters. Self-rated health, depressive symptoms, peace, meaning and faith, and overall QOL were compared at Time 1 and Time 2. Hierarchical and k-means clustering methods both suggested four clusters. Comparison of the four clusters supported statistically significant and clinically meaningful differences in QOL outcomes among clusters while revealing contrasting relations of faith with QOL. Cluster 1, Cluster 3, and Cluster 4 represented high, medium, and low levels of overall QOL, respectively, with correspondingly high, medium, and low levels of peace, meaning, and faith. Cluster 2 was distinguished from other clusters by its medium levels of overall QOL, peace, and meaning and low level of faith. This study provides empirical support for individual difference in response to a newly diagnosed cancer and brings into focus conceptual and methodological challenges associated with the measure of spiritual well-being, which may partly contribute to the attenuated relation between faith and QOL.

Spatial clustering of childhood cancer in Great Britain during the period 1969-1993.

Science.gov (United States)

McNally, Richard J Q; Alexander, Freda E; Vincent, Tim J; Murphy, Michael F G

2009-02-15

The aetiology of childhood cancer is poorly understood. Both genetic and environmental factors are likely to be involved. The presence of spatial clustering is indicative of a very localized environmental component to aetiology. Spatial clustering is present when there are a small number of areas with greatly increased incidence or a large number of areas with moderately increased incidence. To determine whether localized environmental factors may play a part in childhood cancer aetiology, we analyzed for spatial clustering using a large set of national population-based data from Great Britain diagnosed 1969-1993. The Potthoff-Whittinghill method was used to test for extra-Poisson variation (EPV). Thirty-two thousand three hundred and twenty-three cases were allocated to 10,444 wards using diagnosis addresses. Analyses showed statistically significant evidence of clustering for acute lymphoblastic leukaemia (ALL) over the whole age range (estimate of EPV = 0.05, p = 0.002) and for ages 1-4 years (estimate of EPV = 0.03, p = 0.015). Soft-tissue sarcoma (estimate of EPV = 0.03, p = 0.04) and Wilms tumours (estimate of EPV = 0.04, p = 0.007) also showed significant clustering. Clustering tended to persist across different time periods for cases of ALL (estimate of between-time period EPV = 0.04, p =0.003). In conclusion, we observed low level spatial clustering that is attributable to a limited number of cases. This suggests that environmental factors, which in some locations display localized clustering, may be important aetiological agents in these diseases. For ALL and soft tissue sarcoma, but not Wilms tumour, common infectious agents may be likely candidates.

Scaling of cluster growth for coagulating active particles

Science.gov (United States)

Cremer, Peet; Löwen, Hartmut

2014-02-01

Cluster growth in a coagulating system of active particles (such as microswimmers in a solvent) is studied by theory and simulation. In contrast to passive systems, the net velocity of a cluster can have various scalings dependent on the propulsion mechanism and alignment of individual particles. Additionally, the persistence length of the cluster trajectory typically increases with size. As a consequence, a growing cluster collects neighboring particles in a very efficient way and thus amplifies its growth further. This results in unusual large growth exponents for the scaling of the cluster size with time and, for certain conditions, even leads to "explosive" cluster growth where the cluster becomes macroscopic in a finite amount of time.

Unraveling the hidden heterogeneities of breast cancer based on functional miRNA cluster.

Directory of Open Access Journals (Sweden)

Li Li

Full Text Available It has become increasingly clear that the current taxonomy of clinical phenotypes is mixed with molecular heterogeneity, which potentially affects the treatment effect for involved patients. Defining the hidden molecular-distinct diseases using modern large-scale genomic approaches is therefore useful for refining clinical practice and improving intervention strategies. Given that microRNA expression profiling has provided a powerful way to dissect hidden genetic heterogeneity for complex diseases, the aim of the study was to develop a bioinformatics approach that identifies microRNA features leading to the hidden subtyping of complex clinical phenotypes. The basic strategy of the proposed method was to identify optimal miRNA clusters by iteratively partitioning the sample and feature space using the two-ways super-paramagnetic clustering technique. We evaluated the obtained optimal miRNA cluster by determining the consistency of co-expression and the chromosome location among the within-cluster microRNAs, and concluded that the optimal miRNA cluster could lead to a natural partition of disease samples. We applied the proposed method to a publicly available microarray dataset of breast cancer patients that have notoriously heterogeneous phenotypes. We obtained a feature subset of 13 microRNAs that could classify the 71 breast cancer patients into five subtypes with significantly different five-year overall survival rates (45%, 82.4%, 70.6%, 100% and 60% respectively; p = 0.008. By building a multivariate Cox proportional-hazards prediction model for the feature subset, we identified has-miR-146b as one of the most significant predictor (p = 0.045; hazard ratios = 0.39. The proposed algorithm is a promising computational strategy for dissecting hidden genetic heterogeneity for complex diseases, and will be of value for improving cancer diagnosis and treatment.

Symptom clusters in women with breast cancer: an analysis of data from social media and a research study.

Science.gov (United States)

Marshall, Sarah A; Yang, Christopher C; Ping, Qing; Zhao, Mengnan; Avis, Nancy E; Ip, Edward H

2016-03-01

User-generated content on social media sites, such as health-related online forums, offers researchers a tantalizing amount of information, but concerns regarding scientific application of such data remain. This paper compares and contrasts symptom cluster patterns derived from messages on a breast cancer forum with those from a symptom checklist completed by breast cancer survivors participating in a research study. Over 50,000 messages generated by 12,991 users of the breast cancer forum on MedHelp.org were transformed into a standard form and examined for the co-occurrence of 25 symptoms. The k-medoid clustering method was used to determine appropriate placement of symptoms within clusters. Findings were compared with a similar analysis of a symptom checklist administered to 653 breast cancer survivors participating in a research study. The following clusters were identified using forum data: menopausal/psychological, pain/fatigue, gastrointestinal, and miscellaneous. Study data generated the clusters: menopausal, pain, fatigue/sleep/gastrointestinal, psychological, and increased weight/appetite. Although the clusters are somewhat different, many symptoms that clustered together in the social media analysis remained together in the analysis of the study participants. Density of connections between symptoms, as reflected by rates of co-occurrence and similarity, was higher in the study data. The copious amount of data generated by social media outlets can augment findings from traditional data sources. When different sources of information are combined, areas of overlap and discrepancy can be detected, perhaps giving researchers a more accurate picture of reality. However, data derived from social media must be used carefully and with understanding of its limitations.

Up-regulation of HOXB cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells.

Science.gov (United States)

Yang, Seoyeon; Lee, Ji-Yeon; Hur, Ho; Oh, Ji Hoon; Kim, Myoung Hee

2018-05-28

Tamoxifen (TAM) is commonly used to treat estrogen receptor (ER)-positive breast cancer. Despite the remarkable benefits, resistance to TAM presents a serious therapeutic challenge. Since several HOX transcription factors have been proposed as strong candidates in the development of resistance to TAM therapy in breast cancer, we generated an in vitro model of acquired TAM resistance using ER-positive MCF7 breast cancer cells (MCF7-TAMR), and analyzed the expression pattern and epigenetic states of HOX genes. HOXB cluster genes were uniquely up-regulated in MCF7-TAMR cells. Survival analysis of in slico data showed the correlation of high expression of HOXB genes with poor response to TAM in ER-positive breast cancer patients treated with TAM. Gain- and loss-of-function experiments showed that the overexpression of multi HOXB genes in MCF7 renders cancer cells more resistant to TAM, whereas the knockdown restores TAM sensitivity. Furthermore, activation of HOXB genes in MCF7-TAMR was associated with histone modifications, particularly the gain of H3K9ac. These findings imply that the activation of HOXB genes mediate the development of TAM resistance, and represent a target for development of new strategies to prevent or reverse TAM resistance.

Evaluation of secular trend and the existence of cases of clusters of bladder cancer in Goiania: descriptive study population-based; Avaliacao da tendencia temporal e da existencia de casos de clusters de cancer de bexiga em Goiania: estudo descritivo de base populacional

Energy Technology Data Exchange (ETDEWEB)

Antonio, Gisele Guimaraes Daflon

2008-07-01

More than 20 years after the radiological accident with cesium-137 in the city of Goiania, there is still a feeling in local population that the number of cases of cancer in the city is growing up due to the past radiation exposure and that the number of people contaminated or exposed was higher than the number reported. The present study aims to evaluate the temporal trend and the space-time distribution of bladder cancer cases in Goiania from 1988 and 2003, taking into account that bladder cancer presents the highest risk coefficients per unit of radiation dose among solid cancers. The study population was composed of all incident cases of bladder cancer registered in the Population-Based Cancer Registry of Goiania, between 1988 and 2003.Temporal trend of bladder cancer incidence was analyzed by sex and age groups ( < 60 and {>=} 60 years of age) through polynomial regression using age standardized incidence rates of bladder cancer (world population). SaTscan was used to determine whether statistical significant geographic clusters of high incidence of bladder cancer cases can be located in the city. The results showed a significant increase of bladder cancer incidence rates in males of all ages (p= 0.025) and for age group higher or equal to 60 years old (p=O.022), and a stability in trends for female sex. In the space-time analysis, a cluster was identified, however without statistical significance (p=0.278) and its location has no relationship with the main focuses of contamination of the radiological accident in 1987. We concluded that, despite of the increase of incidence rates in males, this can be explained by the improvement in diagnostic procedures throughout time, being this increase still not perceived in females considering the small number of cases. As chance can not be ruled out as the explanation of the identified cluster, we do not suggest any further detailed investigation in this cluster, as the occurrence of cluster diseases in space can occur

Egocentric daily activity recognition via multitask clustering.

Science.gov (United States)

Yan, Yan; Ricci, Elisa; Liu, Gaowen; Sebe, Nicu

2015-10-01

Recognizing human activities from videos is a fundamental research problem in computer vision. Recently, there has been a growing interest in analyzing human behavior from data collected with wearable cameras. First-person cameras continuously record several hours of their wearers' life. To cope with this vast amount of unlabeled and heterogeneous data, novel algorithmic solutions are required. In this paper, we propose a multitask clustering framework for activity of daily living analysis from visual data gathered from wearable cameras. Our intuition is that, even if the data are not annotated, it is possible to exploit the fact that the tasks of recognizing everyday activities of multiple individuals are related, since typically people perform the same actions in similar environments, e.g., people working in an office often read and write documents). In our framework, rather than clustering data from different users separately, we propose to look for clustering partitions which are coherent among related tasks. In particular, two novel multitask clustering algorithms, derived from a common optimization problem, are introduced. Our experimental evaluation, conducted both on synthetic data and on publicly available first-person vision data sets, shows that the proposed approach outperforms several single-task and multitask learning methods.

Clustering self-organizing maps (SOM) method for human papillomavirus (HPV) DNA as the main cause of cervical cancer disease

Science.gov (United States)

Bustamam, A.; Aldila, D.; Fatimah, Arimbi, M. D.

2017-07-01

One of the most widely used clustering method, since it has advantage on its robustness, is Self-Organizing Maps (SOM) method. This paper discusses the application of SOM method on Human Papillomavirus (HPV) DNA which is the main cause of cervical cancer disease, the most dangerous cancer in developing countries. We use 18 types of HPV DNA-based on the newest complete genome. By using open-source-based program R, clustering process can separate 18 types of HPV into two different clusters. There are two types of HPV in the first cluster while 16 others in the second cluster. The analyzing result of 18 types HPV based on the malignancy of the virus (the difficultness to cure). Two of HPV types the first cluster can be classified as tame HPV, while 16 others in the second cluster are classified as vicious HPV.

A cluster expansion model for predicting activation barrier of atomic processes

International Nuclear Information System (INIS)

Rehman, Tafizur; Jaipal, M.; Chatterjee, Abhijit

2013-01-01

We introduce a procedure based on cluster expansion models for predicting the activation barrier of atomic processes encountered while studying the dynamics of a material system using the kinetic Monte Carlo (KMC) method. Starting with an interatomic potential description, a mathematical derivation is presented to show that the local environment dependence of the activation barrier can be captured using cluster interaction models. Next, we develop a systematic procedure for training the cluster interaction model on-the-fly, which involves: (i) obtaining activation barriers for handful local environments using nudged elastic band (NEB) calculations, (ii) identifying the local environment by analyzing the NEB results, and (iii) estimating the cluster interaction model parameters from the activation barrier data. Once a cluster expansion model has been trained, it is used to predict activation barriers without requiring any additional NEB calculations. Numerical studies are performed to validate the cluster expansion model by studying hop processes in Ag/Ag(100). We show that the use of cluster expansion model with KMC enables efficient generation of an accurate process rate catalog

Profiling physical activity motivation based on self-determination theory: a cluster analysis approach.

Science.gov (United States)

Friederichs, Stijn Ah; Bolman, Catherine; Oenema, Anke; Lechner, Lilian

2015-01-01

In order to promote physical activity uptake and maintenance in individuals who do not comply with physical activity guidelines, it is important to increase our understanding of physical activity motivation among this group. The present study aimed to examine motivational profiles in a large sample of adults who do not comply with physical activity guidelines. The sample for this study consisted of 2473 individuals (31.4% male; age 44.6 ± 12.9). In order to generate motivational profiles based on motivational regulation, a cluster analysis was conducted. One-way analyses of variance were then used to compare the clusters in terms of demographics, physical activity level, motivation to be active and subjective experience while being active. Three motivational clusters were derived based on motivational regulation scores: a low motivation cluster, a controlled motivation cluster and an autonomous motivation cluster. These clusters differed significantly from each other with respect to physical activity behavior, motivation to be active and subjective experience while being active. Overall, the autonomous motivation cluster displayed more favorable characteristics compared to the other two clusters. The results of this study provide additional support for the importance of autonomous motivation in the context of physical activity behavior. The three derived clusters may be relevant in the context of physical activity interventions as individuals within the different clusters might benefit most from different intervention approaches. In addition, this study shows that cluster analysis is a useful method for differentiating between motivational profiles in large groups of individuals who do not comply with physical activity guidelines.

Symptoms and Symptom Clusters Identified by Adolescents and Young Adults With Cancer Using a Symptom Heuristics App.

Science.gov (United States)

Ameringer, Suzanne; Erickson, Jeanne M; Macpherson, Catherine Fiona; Stegenga, Kristin; Linder, Lauri A

2015-12-01

Adolescents and young adults (AYAs) with cancer experience multiple distressing symptoms during treatment. Because the typical approach to symptom assessment does not easily reflect the symptom experience of individuals, alternative approaches to enhancing communication between the patient and provider are needed. We developed an iPad-based application that uses a heuristic approach to explore AYAs' cancer symptom experiences. In this mixed-methods descriptive study, 72 AYAs (13-29 years old) with cancer receiving myelosuppressive chemotherapy used the Computerized Symptom Capture Tool (C-SCAT) to create images of the symptoms and symptom clusters they experienced from a list of 30 symptoms. They answered open-ended questions within the C-SCAT about the causes of their symptoms and symptom clusters. The images generated through the C-SCAT and accompanying free-text data were analyzed using descriptive, content, and visual analyses. Most participants (n = 70) reported multiple symptoms (M = 8.14). The most frequently reported symptoms were nausea (65.3%), feeling drowsy (55.6%), lack of appetite (55.6%), and lack of energy (55.6%). Forty-six grouped their symptoms into one or more clusters. The most common symptom cluster was nausea/eating problems/appetite problems. Nausea was most frequently named as the priority symptom in a cluster and as a cause of other symptoms. Although common threads were present in the symptoms experienced by AYAs, the graphic images revealed unique perspectives and a range of complexity of symptom relationships, clusters, and causes. Results highlight the need for a tailored approach to symptom management based on how the AYA with cancer perceives his or her symptom experience. © 2015 Wiley Periodicals, Inc.

Identifying clusters of active transportation using spatial scan statistics.

Science.gov (United States)

Huang, Lan; Stinchcomb, David G; Pickle, Linda W; Dill, Jennifer; Berrigan, David

2009-08-01

There is an intense interest in the possibility that neighborhood characteristics influence active transportation such as walking or biking. The purpose of this paper is to illustrate how a spatial cluster identification method can evaluate the geographic variation of active transportation and identify neighborhoods with unusually high/low levels of active transportation. Self-reported walking/biking prevalence, demographic characteristics, street connectivity variables, and neighborhood socioeconomic data were collected from respondents to the 2001 California Health Interview Survey (CHIS; N=10,688) in Los Angeles County (LAC) and San Diego County (SDC). Spatial scan statistics were used to identify clusters of high or low prevalence (with and without age-adjustment) and the quantity of time spent walking and biking. The data, a subset from the 2001 CHIS, were analyzed in 2007-2008. Geographic clusters of significantly high or low prevalence of walking and biking were detected in LAC and SDC. Structural variables such as street connectivity and shorter block lengths are consistently associated with higher levels of active transportation, but associations between active transportation and socioeconomic variables at the individual and neighborhood levels are mixed. Only one cluster with less time spent walking and biking among walkers/bikers was detected in LAC, and this was of borderline significance. Age-adjustment affects the clustering pattern of walking/biking prevalence in LAC, but not in SDC. The use of spatial scan statistics to identify significant clustering of health behaviors such as active transportation adds to the more traditional regression analysis that examines associations between behavior and environmental factors by identifying specific geographic areas with unusual levels of the behavior independent of predefined administrative units.

Identification of new candidate drugs for lung cancer using chemical-chemical interactions, chemical-protein interactions and a K-means clustering algorithm.

Science.gov (United States)

Lu, Jing; Chen, Lei; Yin, Jun; Huang, Tao; Bi, Yi; Kong, Xiangyin; Zheng, Mingyue; Cai, Yu-Dong

2016-01-01

Lung cancer, characterized by uncontrolled cell growth in the lung tissue, is the leading cause of global cancer deaths. Until now, effective treatment of this disease is limited. Many synthetic compounds have emerged with the advancement of combinatorial chemistry. Identification of effective lung cancer candidate drug compounds among them is a great challenge. Thus, it is necessary to build effective computational methods that can assist us in selecting for potential lung cancer drug compounds. In this study, a computational method was proposed to tackle this problem. The chemical-chemical interactions and chemical-protein interactions were utilized to select candidate drug compounds that have close associations with approved lung cancer drugs and lung cancer-related genes. A permutation test and K-means clustering algorithm were employed to exclude candidate drugs with low possibilities to treat lung cancer. The final analysis suggests that the remaining drug compounds have potential anti-lung cancer activities and most of them have structural dissimilarity with approved drugs for lung cancer.

Effect of mitochondrial complex I inhibition on Fe-S cluster protein activity

Energy Technology Data Exchange (ETDEWEB)

Mena, Natalia P. [Department of Biology, Faculty of Sciences, Universidad de Chile, Las Palmeras 3425, Santiago (Chile); Millennium Institute of Cell Dynamics and Biotechnology, Santiago (Chile); Bulteau, Anne Laure [UPMC Univ Paris 06, UMRS 975 - UMR 7725, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); Inserm, U 975, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); CNRS, UMR 7225, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, Paris 75013 (France); Salazar, Julio [Millennium Institute of Cell Dynamics and Biotechnology, Santiago (Chile); Hirsch, Etienne C. [UPMC Univ Paris 06, UMRS 975 - UMR 7725, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); Inserm, U 975, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); CNRS, UMR 7225, Centre de Recherche en Neurosciences, ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, F-75005 Paris (France); ICM, Therapeutique Experimentale de la Neurodegenerescence, Hopital de la Salpetriere, Paris 75013 (France); Nunez, Marco T., E-mail: mnunez@uchile.cl [Department of Biology, Faculty of Sciences, Universidad de Chile, Las Palmeras 3425, Santiago (Chile); Millennium Institute of Cell Dynamics and Biotechnology, Santiago (Chile)

2011-06-03

Highlights: {yields} Mitochondrial complex I inhibition resulted in decreased activity of Fe-S containing enzymes mitochondrial aconitase and cytoplasmic aconitase and xanthine oxidase. {yields} Complex I inhibition resulted in the loss of Fe-S clusters in cytoplasmic aconitase and of glutamine phosphoribosyl pyrophosphate amidotransferase. {yields} Consistent with loss of cytoplasmic aconitase activity, an increase in iron regulatory protein 1 activity was found. {yields} Complex I inhibition resulted in an increase in the labile cytoplasmic iron pool. -- Abstract: Iron-sulfur (Fe-S) clusters are small inorganic cofactors formed by tetrahedral coordination of iron atoms with sulfur groups. Present in numerous proteins, these clusters are involved in key biological processes such as electron transfer, metabolic and regulatory processes, DNA synthesis and repair and protein structure stabilization. Fe-S clusters are synthesized mainly in the mitochondrion, where they are directly incorporated into mitochondrial Fe-S cluster-containing proteins or exported for cytoplasmic and nuclear cluster-protein assembly. In this study, we tested the hypothesis that inhibition of mitochondrial complex I by rotenone decreases Fe-S cluster synthesis and cluster content and activity of Fe-S cluster-containing enzymes. Inhibition of complex I resulted in decreased activity of three Fe-S cluster-containing enzymes: mitochondrial and cytosolic aconitases and xanthine oxidase. In addition, the Fe-S cluster content of glutamine phosphoribosyl pyrophosphate amidotransferase and mitochondrial aconitase was dramatically decreased. The reduction in cytosolic aconitase activity was associated with an increase in iron regulatory protein (IRP) mRNA binding activity and with an increase in the cytoplasmic labile iron pool. Since IRP activity post-transcriptionally regulates the expression of iron import proteins, Fe-S cluster inhibition may result in a false iron deficiency signal. Given that

Effect of mitochondrial complex I inhibition on Fe-S cluster protein activity

International Nuclear Information System (INIS)

Mena, Natalia P.; Bulteau, Anne Laure; Salazar, Julio; Hirsch, Etienne C.; Nunez, Marco T.

2011-01-01

Highlights: → Mitochondrial complex I inhibition resulted in decreased activity of Fe-S containing enzymes mitochondrial aconitase and cytoplasmic aconitase and xanthine oxidase. → Complex I inhibition resulted in the loss of Fe-S clusters in cytoplasmic aconitase and of glutamine phosphoribosyl pyrophosphate amidotransferase. → Consistent with loss of cytoplasmic aconitase activity, an increase in iron regulatory protein 1 activity was found. → Complex I inhibition resulted in an increase in the labile cytoplasmic iron pool. -- Abstract: Iron-sulfur (Fe-S) clusters are small inorganic cofactors formed by tetrahedral coordination of iron atoms with sulfur groups. Present in numerous proteins, these clusters are involved in key biological processes such as electron transfer, metabolic and regulatory processes, DNA synthesis and repair and protein structure stabilization. Fe-S clusters are synthesized mainly in the mitochondrion, where they are directly incorporated into mitochondrial Fe-S cluster-containing proteins or exported for cytoplasmic and nuclear cluster-protein assembly. In this study, we tested the hypothesis that inhibition of mitochondrial complex I by rotenone decreases Fe-S cluster synthesis and cluster content and activity of Fe-S cluster-containing enzymes. Inhibition of complex I resulted in decreased activity of three Fe-S cluster-containing enzymes: mitochondrial and cytosolic aconitases and xanthine oxidase. In addition, the Fe-S cluster content of glutamine phosphoribosyl pyrophosphate amidotransferase and mitochondrial aconitase was dramatically decreased. The reduction in cytosolic aconitase activity was associated with an increase in iron regulatory protein (IRP) mRNA binding activity and with an increase in the cytoplasmic labile iron pool. Since IRP activity post-transcriptionally regulates the expression of iron import proteins, Fe-S cluster inhibition may result in a false iron deficiency signal. Given that inhibition of complex

Association of Inflammatory Cytokines With the Symptom Cluster of Pain, Fatigue, Depression, and Sleep Disturbance in Chinese Patients With Cancer.

Science.gov (United States)

Ji, Yan-Bo; Bo, Chun-Lu; Xue, Xiu-Juan; Weng, En-Ming; Gao, Guang-Chao; Dai, Bei-Bei; Ding, Kai-Wen; Xu, Cui-Ping

2017-12-01

Pain, fatigue, depression, and sleep disturbance are common in patients with cancer and usually co-occur as a symptom cluster. However, the mechanism underlying this symptom cluster is unclear. This study aimed to identify subgroups of cluster symptoms, compare demographic and clinical characteristics between subgroups, and examine the associations between inflammatory cytokines and cluster symptoms. Participants were 170 Chinese inpatients with cancer from two tertiary hospitals. Inflammatory markers including interleukin-6 (IL-6), interleukin-1 receptor antagonist, and tumor necrosis factor alpha were measured. Intergroup differences and associations of inflammatory cytokines with the cluster symptoms were examined with one-way analyses of variance and logistic regression. Based on cluster analysis, participants were categorized into Subgroup 1 (all low symptoms), Subgroup 2 (low pain and moderate fatigue), or Subgroup 3 (moderate-to-high on all symptoms). The three subgroups differed significantly in Eastern Cooperative Oncology Group (ECOG) performance status, sex, residence, current treatment, education, economic status, and inflammatory cytokines levels (all P cluster symptoms in cancer patients. Clinicians should identify patients at risk for more severe symptoms and formulate novel target interventions to improve symptom management. Copyright © 2017. Published by Elsevier Inc.

Unsupervised active learning based on hierarchical graph-theoretic clustering.

Science.gov (United States)

Hu, Weiming; Hu, Wei; Xie, Nianhua; Maybank, Steve

2009-10-01

Most existing active learning approaches are supervised. Supervised active learning has the following problems: inefficiency in dealing with the semantic gap between the distribution of samples in the feature space and their labels, lack of ability in selecting new samples that belong to new categories that have not yet appeared in the training samples, and lack of adaptability to changes in the semantic interpretation of sample categories. To tackle these problems, we propose an unsupervised active learning framework based on hierarchical graph-theoretic clustering. In the framework, two promising graph-theoretic clustering algorithms, namely, dominant-set clustering and spectral clustering, are combined in a hierarchical fashion. Our framework has some advantages, such as ease of implementation, flexibility in architecture, and adaptability to changes in the labeling. Evaluations on data sets for network intrusion detection, image classification, and video classification have demonstrated that our active learning framework can effectively reduce the workload of manual classification while maintaining a high accuracy of automatic classification. It is shown that, overall, our framework outperforms the support-vector-machine-based supervised active learning, particularly in terms of dealing much more efficiently with new samples whose categories have not yet appeared in the training samples.

Symptom clusters of ovarian cancer patients undergoing chemotherapy, and their emotional status and quality of life.

Science.gov (United States)

Hwang, Kyung-Hye; Cho, Ok-Hee; Yoo, Yang-Sook

2016-04-01

We conducted a descriptive study to identify the symptoms, emotional status, and quality of life experienced by hospitalized ovarian cancer patients undergoing chemotherapy, and influencing the factors of symptom clusters on their quality of life. A total of 192 patients who had been diagnosed with ovarian cancer and received adjuvant chemotherapy after surgery more than once from 2 university hospitals with over 800 beds located in the Seoul and Gyeonggi areas of South Korea were included in this study. Using a structured questionnaire, the symptoms, emotional status, and quality of life by these patients were investigated from May 2012 to June 2013. We identified the following 7 symptom clusters among ovarian cancer patients undergoing chemotherapy: psychological distress, fatigue-pain, abdominal discomfort, flu-like symptoms, fluid accumulation, and peripheral neuropathy. Patients with a high level of anxiety or depression experienced all symptoms at a higher level, and the 7 symptom clusters influenced all aspects of the patients' quality of life. This study provides to need interventions for the quality of life of ovarian cancer patients need to include the management of not only the physical symptoms and treatment-related side effects, but also the changes in their emotional status and daily lives. Copyright © 2015 Elsevier Ltd. All rights reserved.

Physical Activity and Cancer

Science.gov (United States)

... Cancer Genetics Services Directory Cancer Prevention Overview Research Physical Activity and Cancer On This Page What is physical activity? What is known about the relationship between physical ...

Prediction of chemotherapeutic response in bladder cancer using K-means clustering of dynamic contrast-enhanced (DCE)-MRI pharmacokinetic parameters.

Science.gov (United States)

Nguyen, Huyen T; Jia, Guang; Shah, Zarine K; Pohar, Kamal; Mortazavi, Amir; Zynger, Debra L; Wei, Lai; Yang, Xiangyu; Clark, Daniel; Knopp, Michael V

2015-05-01

To apply k-means clustering of two pharmacokinetic parameters derived from 3T dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict the chemotherapeutic response in bladder cancer at the mid-cycle timepoint. With the predetermined number of three clusters, k-means clustering was performed on nondimensionalized Amp and kep estimates of each bladder tumor. Three cluster volume fractions (VFs) were calculated for each tumor at baseline and mid-cycle. The changes of three cluster VFs from baseline to mid-cycle were correlated with the tumor's chemotherapeutic response. Receiver-operating-characteristics curve analysis was used to evaluate the performance of each cluster VF change as a biomarker of chemotherapeutic response in bladder cancer. The k-means clustering partitioned each bladder tumor into cluster 1 (low kep and low Amp), cluster 2 (low kep and high Amp), cluster 3 (high kep and low Amp). The changes of all three cluster VFs were found to be associated with bladder tumor response to chemotherapy. The VF change of cluster 2 presented with the highest area-under-the-curve value (0.96) and the highest sensitivity/specificity/accuracy (96%/100%/97%) with a selected cutoff value. The k-means clustering of the two DCE-MRI pharmacokinetic parameters can characterize the complex microcirculatory changes within a bladder tumor to enable early prediction of the tumor's chemotherapeutic response. © 2014 Wiley Periodicals, Inc.

18F-FDG PET radiomics approaches: comparing and clustering features in cervical cancer.

Science.gov (United States)

Tsujikawa, Tetsuya; Rahman, Tasmiah; Yamamoto, Makoto; Yamada, Shizuka; Tsuyoshi, Hideaki; Kiyono, Yasushi; Kimura, Hirohiko; Yoshida, Yoshio; Okazawa, Hidehiko

2017-11-01

The aims of our study were to find the textural features on 18 F-FDG PET/CT which reflect the different histological architectures between cervical cancer subtypes and to make a visual assessment of the association between 18 F-FDG PET textural features in cervical cancer. Eighty-three cervical cancer patients [62 squamous cell carcinomas (SCCs) and 21 non-SCCs (NSCCs)] who had undergone pretreatment 18 F-FDG PET/CT were enrolled. A texture analysis was performed on PET/CT images, from which 18 PET radiomics features were extracted including first-order features such as standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG), second- and high-order textural features using SUV histogram, normalized gray-level co-occurrence matrix (NGLCM), and neighborhood gray-tone difference matrix, respectively. These features were compared between SCC and NSCC using a Bonferroni adjusted P value threshold of 0.0028 (0.05/18). To assess the association between PET features, a heat map analysis with hierarchical clustering, one of the radiomics approaches, was performed. Among 18 PET features, correlation, a second-order textural feature derived from NGLCM, was a stable parameter and it was the only feature which showed a robust trend toward significant difference between SCC and NSCC. Cervical SCC showed a higher correlation (0.70 ± 0.07) than NSCC (0.64 ± 0.07, P = 0.0030). The other PET features did not show any significant differences between SCC and NSCC. A higher correlation in SCC might reflect higher structural integrity and stronger spatial/linear relationship of cancer cells compared with NSCC. A heat map with a PET feature dendrogram clearly showed 5 distinct clusters, where correlation belonged to a cluster including MTV and TLG. However, the association between correlation and MTV/TLG was not strong. Correlation was a relatively independent PET feature in cervical cancer. 18 F-FDG PET textural features might reflect the

Cancer Clusters

Science.gov (United States)

... and number of cases of each type, the age of the people with cancer, and the area and time period over which the cancers were diagnosed. They also ask about specific environmental hazards or concerns in the affected area. If the review of ...

Cancer, Physical Activity, and Exercise

Science.gov (United States)

Brown, Justin C.; Winters-Stone, Kerri; Lee, Augustine; Schmitz, Kathryn H.

2014-01-01

This review examines the relationship between physical activity and cancer along the cancer continuum, and serves as a synthesis of systematic and meta-analytic reviews conducted to date. There exists a large body of epidemiologic evidence that conclude those who participate in higher levels of physical activity have a reduced likelihood of developing a variety of cancers compared to those who engage in lower levels of physical activity. Despite this observational evidence, the causal pathway underling the association between participation in physical activity and cancer risk reduction remains unclear. Physical activity is also a useful adjunct to improve the deleterious sequelae experienced during cancer treatment. These deleterious sequelae may include fatigue, muscular weakness, deteriorated functional capacity, including many others. The benefits of physical activity during cancer treatment are similar to those experienced after treatment. Despite the growing volume of literature examining physical activity and cancer across the cancer continuum, a number of research gaps exist. There is little evidence on the safety of physical activity among all cancer survivors, as most trials have selectively recruited participants. It is also unclear the specific dose of exercise needed that is optimal for primary cancer prevention or symptom control during and after cancer treatment. PMID:23720265

Pharmacokinetic analysis and k-means clustering of DCEMR images for radiotherapy outcome prediction of advanced cervical cancers.

Science.gov (United States)

Andersen, Erlend K F; Kristensen, Gunnar B; Lyng, Heidi; Malinen, Eirik

2011-08-01

Pharmacokinetic analysis of dynamic contrast enhanced magnetic resonance images (DCEMRI) allows for quantitative characterization of vascular properties of tumors. The aim of this study is twofold, first to determine if tumor regions with similar vascularization could be labeled by clustering methods, second to determine if the identified regions can be associated with local cancer relapse. Eighty-one patients with locally advanced cervical cancer treated with chemoradiotherapy underwent DCEMRI with Gd-DTPA prior to external beam radiotherapy. The median follow-up time after treatment was four years, in which nine patients had primary tumor relapse. By fitting a pharmacokinetic two-compartment model function to the temporal contrast enhancement in the tumor, two pharmacokinetic parameters, K(trans) and ύ(e), were estimated voxel by voxel from the DCEMR-images. Intratumoral regions with similar vascularization were identified by k-means clustering of the two pharmacokinetic parameter estimates over all patients. The volume fraction of each cluster was used to evaluate the prognostic value of the clusters. Three clusters provided a sufficient reduction of the cluster variance to label different vascular properties within the tumors. The corresponding median volume fraction of each cluster was 38%, 46% and 10%. The second cluster was significantly associated with primary tumor control in a log-rank survival test (p-value: 0.042), showing a decreased risk of treatment failure for patients with high volume fraction of voxels. Intratumoral regions showing similar vascular properties could successfully be labeled in three distinct clusters and the volume fraction of one cluster region was associated with primary tumor control.

Pharmacokinetic analysis and k-means clustering of DCEMR images for radiotherapy outcome prediction of advanced cervical cancers

International Nuclear Information System (INIS)

Andersen, Erlend K. F.; Kristensen, Gunnar B.; Lyng, Heidi; Malinen, Eirik

2011-01-01

Introduction. Pharmacokinetic analysis of dynamic contrast enhanced magnetic resonance images (DCEMRI) allows for quantitative characterization of vascular properties of tumors. The aim of this study is twofold, first to determine if tumor regions with similar vascularization could be labeled by clustering methods, second to determine if the identified regions can be associated with local cancer relapse. Materials and methods. Eighty-one patients with locally advanced cervical cancer treated with chemoradiotherapy underwent DCEMRI with Gd-DTPA prior to external beam radiotherapy. The median follow-up time after treatment was four years, in which nine patients had primary tumor relapse. By fitting a pharmacokinetic two-compartment model function to the temporal contrast enhancement in the tumor, two pharmacokinetic parameters, K trans and u e , were estimated voxel by voxel from the DCEMR-images. Intratumoral regions with similar vascularization were identified by k-means clustering of the two pharmacokinetic parameter estimates over all patients. The volume fraction of each cluster was used to evaluate the prognostic value of the clusters. Results. Three clusters provided a sufficient reduction of the cluster variance to label different vascular properties within the tumors. The corresponding median volume fraction of each cluster was 38%, 46% and 10%. The second cluster was significantly associated with primary tumor control in a log-rank survival test (p-value: 0.042), showing a decreased risk of treatment failure for patients with high volume fraction of voxels. Conclusions. Intratumoral regions showing similar vascular properties could successfully be labeled in three distinct clusters and the volume fraction of one cluster region was associated with primary tumor control

Pharmacokinetic analysis and k-means clustering of DCEMR images for radiotherapy outcome prediction of advanced cervical cancers

Energy Technology Data Exchange (ETDEWEB)

Andersen, Erlend K. F. (Dept. of Medical Physics, The Norwegian Radium Hospital, Oslo Univ. Hospital, Oslo (Norway)), e-mail: eirik.malinen@fys.uio.no; Kristensen, Gunnar B. (Section for Gynaecological Oncology, The Norwegian Radium Hospital, Oslo Univ. Hospital, Oslo (Norway)); Lyng, Heidi (Dept. of Radiation Biology, The Norwegian Radium Hospital, Oslo Univ. Hospital, Oslo (Norway)); Malinen, Eirik (Dept. of Medical Physics, The Norwegian Radium Hospital, Oslo Univ. Hospital, Oslo (Norway); Dept. of Physics, Univ. of Oslo, Oslo (Norway))

2011-08-15

Introduction. Pharmacokinetic analysis of dynamic contrast enhanced magnetic resonance images (DCEMRI) allows for quantitative characterization of vascular properties of tumors. The aim of this study is twofold, first to determine if tumor regions with similar vascularization could be labeled by clustering methods, second to determine if the identified regions can be associated with local cancer relapse. Materials and methods. Eighty-one patients with locally advanced cervical cancer treated with chemoradiotherapy underwent DCEMRI with Gd-DTPA prior to external beam radiotherapy. The median follow-up time after treatment was four years, in which nine patients had primary tumor relapse. By fitting a pharmacokinetic two-compartment model function to the temporal contrast enhancement in the tumor, two pharmacokinetic parameters, Ktrans and u{sub e}, were estimated voxel by voxel from the DCEMR-images. Intratumoral regions with similar vascularization were identified by k-means clustering of the two pharmacokinetic parameter estimates over all patients. The volume fraction of each cluster was used to evaluate the prognostic value of the clusters. Results. Three clusters provided a sufficient reduction of the cluster variance to label different vascular properties within the tumors. The corresponding median volume fraction of each cluster was 38%, 46% and 10%. The second cluster was significantly associated with primary tumor control in a log-rank survival test (p-value: 0.042), showing a decreased risk of treatment failure for patients with high volume fraction of voxels. Conclusions. Intratumoral regions showing similar vascular properties could successfully be labeled in three distinct clusters and the volume fraction of one cluster region was associated with primary tumor control

Cluster analysis of activity-time series in motor learning

DEFF Research Database (Denmark)

Balslev, Daniela; Nielsen, Finn Å; Futiger, Sally A

2002-01-01

Neuroimaging studies of learning focus on brain areas where the activity changes as a function of time. To circumvent the difficult problem of model selection, we used a data-driven analytic tool, cluster analysis, which extracts representative temporal and spatial patterns from the voxel......-time series. The optimal number of clusters was chosen using a cross-validated likelihood method, which highlights the clustering pattern that generalizes best over the subjects. Data were acquired with PET at different time points during practice of a visuomotor task. The results from cluster analysis show...

Multifunctional fluorescent iron quantum clusters for non-invasive radiofrequency ablationof cancer cells.

Science.gov (United States)

Jose, Akhila; Surendran, Mrudula; Fazal, Sajid; Prasanth, Bindhu-Paul; Menon, Deepthy

2018-05-01

This work reports the potential of iron quantum clusters (FeQCs) as a hyperthermia agent for cancer, by testing its in-vitro response to shortwave (MHz range), radiofrequency (RF) waves non-invasively. Stable, fluorescent FeQCs of size ∼1 nm prepared by facile aqueous chemistry from endogenous protein haemoglobin were found to give a high thermal response, with a ΔT ∼50 °C at concentrationsas low as165 μg/mL. The as-prepared nanoclusters purified by lyophilization as well as dialysis showed a concentration, power and time-dependent RF response, with the lyophilized FeQCs exhibiting pronounced heating effects. FeQCs were found to be cytocompatible to NIH-3T3 fibroblast and 4T1 cancer cells treated at concentrations upto 1000 μg/mL for 24 h. Upon incubation with FeQCs and exposure to RF waves, significant cancer cell death was observed which proves its therapeutic ability. The fluorescent ability of the clusters could additionally be utilized for imaging cancer cells upon excitation at ∼450 nm. Further, to demonstrate the feasibility of imparting additional functionality such as drug/biomolecule/dye loading to FeQCs, they were self assembled with cationic polymers to form nanoparticles. Self assembly did not alter the RF heating potential of FeQCs and additionally enhanced its fluorescence. The multifunctional fluorescent FeQCs therefore show good promise as a novel therapeutic agent for RF hyperthermia and drug loading. Copyright © 2018 Elsevier B.V. All rights reserved.

Vacancy clustering and acceptor activation in nitrogen-implanted ZnO

Science.gov (United States)

Børseth, Thomas Moe; Tuomisto, Filip; Christensen, Jens S.; Monakhov, Edouard V.; Svensson, Bengt G.; Kuznetsov, Andrej Yu.

2008-01-01

The role of vacancy clustering and acceptor activation on resistivity evolution in N ion-implanted n -type hydrothermally grown bulk ZnO has been investigated by positron annihilation spectroscopy, resistivity measurements, and chemical profiling. Room temperature 220keV N implantation using doses in the low 1015cm-2 range induces small and big vacancy clusters containing at least 2 and 3-4 Zn vacancies, respectively. The small clusters are present already in as-implanted samples and remain stable up to 1000°C with no significant effect on the resistivity evolution. In contrast, formation of the big clusters at 600°C is associated with a significant increase in the free electron concentration attributed to gettering of amphoteric Li impurities by these clusters. Further annealing at 800°C results in a dramatic decrease in the free electron concentration correlated with activation of 1016-1017cm-3 acceptors likely to be N and/or Li related. The samples remain n type, however, and further annealing at 1000°C results in passivation of the acceptor states while the big clusters dissociate.

Active Semisupervised Clustering Algorithm with Label Propagation for Imbalanced and Multidensity Datasets

Directory of Open Access Journals (Sweden)

Mingwei Leng

2013-01-01

Full Text Available The accuracy of most of the existing semisupervised clustering algorithms based on small size of labeled dataset is low when dealing with multidensity and imbalanced datasets, and labeling data is quite expensive and time consuming in many real-world applications. This paper focuses on active data selection and semisupervised clustering algorithm in multidensity and imbalanced datasets and proposes an active semisupervised clustering algorithm. The proposed algorithm uses an active mechanism for data selection to minimize the amount of labeled data, and it utilizes multithreshold to expand labeled datasets on multidensity and imbalanced datasets. Three standard datasets and one synthetic dataset are used to demonstrate the proposed algorithm, and the experimental results show that the proposed semisupervised clustering algorithm has a higher accuracy and a more stable performance in comparison to other clustering and semisupervised clustering algorithms, especially when the datasets are multidensity and imbalanced.

Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence.

Science.gov (United States)

Kerr, Jacqueline; Anderson, Cheryl; Lippman, Scott M

2017-08-01

The lifestyle factors of physical activity, sedentary behaviour, and diet are increasingly being studied for their associations with cancer. Physical activity is inversely associated with and sedentary behaviour is positively (and independently) associated with an increased risk of more than ten types of cancer, including colorectal cancer (and advanced adenomas), endometrial cancers, and breast cancer. The most consistent dietary risk factor for premalignant and invasive breast cancer is alcohol, whether consumed during early or late adult life, even at low levels. Epidemiological studies show that the inclusion of wholegrain, fibre, fruits, and vegetables within diets are associated with reduced cancer risk, with diet during early life (age diet-related factors have not yet shown any conclusive associations between diet and cancer incidence. Obesity is a key contributory factor associated with cancer risk and mortality, including in dose-response associations in endometrial and post-menopausal breast cancer, and in degree and duration of fatty liver disease-related hepatocellular carcinoma. Obesity produces an inflammatory state, characterised by macrophages clustered around enlarged hypertrophied, dead, and dying adipocytes, forming crown-like structures. Increased concentrations of aromatase and interleukin 6 in inflamed breast tissue and an increased number of macrophages, compared with healthy tissue, are also observed in women with normal body mass index, suggesting a metabolic obesity state. Emerging randomised controlled trials of physical activity and dietary factors and mechanistic studies of immunity, inflammation, extracellular matrix mechanics, epigenetic or transcriptional regulation, protein translation, circadian disruption, and interactions of the multibiome with lifestyle factors will be crucial to advance this field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Thermal activation in statistical clusters of magnetic nanoparticles

International Nuclear Information System (INIS)

Hovorka, O

2017-01-01

This article presents a kinetic Monte-Carlo study of thermally activated magnetisation dynamics in clusters of statistically distributed magnetic nanoparticles. The structure of clusters is assumed to be of fractal nature, consistently with recent observations of magnetic particle aggregation in cellular environments. The computed magnetisation relaxation decay and frequency-dependent hysteresis loops are seen to significantly depend on the fractal dimension of aggregates, leading to accelerated magnetisation relaxation and reduction in the size of hysteresis loops as the fractal dimension increases from one-dimensional-like to three-dimensional-like clusters. Discussed are implications for applications in nanomedicine, such as magnetic hyperthermia or magnetic particle imaging. (paper)

Cluster detection methods applied to the Upper Cape Cod cancer data

Directory of Open Access Journals (Sweden)

Ozonoff David

2005-09-01

Full Text Available Abstract Background A variety of statistical methods have been suggested to assess the degree and/or the location of spatial clustering of disease cases. However, there is relatively little in the literature devoted to comparison and critique of different methods. Most of the available comparative studies rely on simulated data rather than real data sets. Methods We have chosen three methods currently used for examining spatial disease patterns: the M-statistic of Bonetti and Pagano; the Generalized Additive Model (GAM method as applied by Webster; and Kulldorff's spatial scan statistic. We apply these statistics to analyze breast cancer data from the Upper Cape Cancer Incidence Study using three different latency assumptions. Results The three different latency assumptions produced three different spatial patterns of cases and controls. For 20 year latency, all three methods generally concur. However, for 15 year latency and no latency assumptions, the methods produce different results when testing for global clustering. Conclusion The comparative analyses of real data sets by different statistical methods provides insight into directions for further research. We suggest a research program designed around examining real data sets to guide focused investigation of relevant features using simulated data, for the purpose of understanding how to interpret statistical methods applied to epidemiological data with a spatial component.

Clinicians' Perspectives on Managing Symptom Clusters in Advanced Cancer: A Semistructured Interview Study.

Science.gov (United States)

Dong, Skye T; Butow, Phyllis N; Agar, Meera; Lovell, Melanie R; Boyle, Frances; Stockler, Martin; Forster, Benjamin C; Tong, Allison

2016-04-01

Managing symptom clusters or multiple concurrent symptoms in patients with advanced cancer remains a clinical challenge. The optimal processes constituting effective management of symptom clusters remain uncertain. To describe the attitudes and strategies of clinicians in managing multiple co-occurring symptoms in patients with advanced cancer. Semistructured interviews were conducted with 48 clinicians (palliative care physicians [n = 10], oncologists [n = 6], general practitioners [n = 6], nurses [n = 12], and allied health providers [n = 14]), purposively recruited from two acute hospitals, two palliative care centers, and four community general practices in Sydney, Australia. Transcripts were analyzed using thematic analysis and adapted grounded theory. Six themes were identified: uncertainty in decision making (inadequacy of scientific evidence, relying on experiential knowledge, and pressure to optimize care); attunement to patient and family (sensitivity to multiple cues, prioritizing individual preferences, addressing psychosocial and physical interactions, and opening Pandora's box); deciphering cause to guide intervention (disaggregating symptoms and interactions, flexibility in assessment, and curtailing investigative intrusiveness); balancing complexities in medical management (trading off side effects, minimizing mismatched goals, and urgency in resolving severe symptoms); fostering hope and empowerment (allaying fear of the unknown, encouraging meaning making, championing patient empowerment, and truth telling); and depending on multidisciplinary expertise (maximizing knowledge exchange, sharing management responsibility, contending with hierarchical tensions, and isolation and discontinuity of care). Management of symptom clusters, as both an art and a science, is currently fraught with uncertainty in decision making. Strengthening multidisciplinary collaboration, continuity of care, more pragmatic planning of clinical trials to address more than one

Symptom clusters in cancer patients and their relation to EGFR ligand modulation of the circadian axis.

Science.gov (United States)

Rich, Tyvin A

2007-04-01

Recent studies in chronobiology and the neurosciences have led to rapid growth in our understanding of the molecular biology of the human timekeeping apparatus and the neuroanatomic sites involved in signaling between the "master clock" in the hypothalamus and other parts of the brain. The circadian axis comprises a central clock mechanism and a downstream network of hypothalamic relay stations that modulate arousal, feeding, and sleeping behavior. Communication between the clock and these hypothalamic signaling centers is mediated, in part, by diffusible substances that include ligands of the epidermal growth factor receptor (EGFR). Preclinical studies reveal that EGFR ligands such as transforming growth factor-alpha (TGF-alpha) inhibit hypothalamic signaling of rhythmic behavior; clinical observations show that elevated levels of TGF-alpha are associated with fatigue, flattened circadian rhythms, and loss of appetite in patients with metastatic colorectal cancer. These data support the hypothesis that a symptom cluster of fatigue, appetite loss, and sleep disruption commonly seen in cancer patients may be related to EGFR ligands, released either by the cancer itself or by the host in response to the stress of cancer, and suggest that further examination of their role in the production of symptom clustering is warranted.

a Three-Step Spatial-Temporal Clustering Method for Human Activity Pattern Analysis

Science.gov (United States)

Huang, W.; Li, S.; Xu, S.

2016-06-01

How people move in cities and what they do in various locations at different times form human activity patterns. Human activity pattern plays a key role in in urban planning, traffic forecasting, public health and safety, emergency response, friend recommendation, and so on. Therefore, scholars from different fields, such as social science, geography, transportation, physics and computer science, have made great efforts in modelling and analysing human activity patterns or human mobility patterns. One of the essential tasks in such studies is to find the locations or places where individuals stay to perform some kind of activities before further activity pattern analysis. In the era of Big Data, the emerging of social media along with wearable devices enables human activity data to be collected more easily and efficiently. Furthermore, the dimension of the accessible human activity data has been extended from two to three (space or space-time) to four dimensions (space, time and semantics). More specifically, not only a location and time that people stay and spend are collected, but also what people "say" for in a location at a time can be obtained. The characteristics of these datasets shed new light on the analysis of human mobility, where some of new methodologies should be accordingly developed to handle them. Traditional methods such as neural networks, statistics and clustering have been applied to study human activity patterns using geosocial media data. Among them, clustering methods have been widely used to analyse spatiotemporal patterns. However, to our best knowledge, few of clustering algorithms are specifically developed for handling the datasets that contain spatial, temporal and semantic aspects all together. In this work, we propose a three-step human activity clustering method based on space, time and semantics to fill this gap. One-year Twitter data, posted in Toronto, Canada, is used to test the clustering-based method. The results show that the

c-Myc activates BRCA1 gene expression through distal promoter elements in breast cancer cells

International Nuclear Information System (INIS)

Chen, Yinghua; Xu, Jinhua; Borowicz, Stanley; Collins, Cindy; Huo, Dezheng; Olopade, Olufunmilayo I

2011-01-01

The BRCA1 gene plays an important role in the maintenance of genomic stability. BRCA1 inactivation contributes to breast cancer tumorigenesis. An increasing number of transcription factors have been shown to regulate BRCA1 expression. c-Myc can act as a transcriptional activator, regulating up to 15% of all genes in the human genome and results from a high throughput screen suggest that BRCA1 is one of its targets. In this report, we used cultured breast cancer cells to examine the mechanisms of transcriptional activation of BRCA1 by c-Myc. c-Myc was depleted using c-Myc-specific siRNAs in cultured breast cancer cells. BRCA1 mRNA expression and BRCA1 protein expression were determined by quantitative RT-PCR and western blot, respectively and BRCA1 promoter activities were examined under these conditions. DNA sequence analysis was conducted to search for high similarity to E boxes in the BRCA1 promoter region. The association of c-Myc with the BRCA1 promoter in vivo was tested by a chromatin immunoprecipitation assay. We investigated the function of the c-Myc binding site in the BRCA1 promoter region by a promoter assay with nucleotide substitutions in the putative E boxes. BRCA1-dependent DNA repair activities were measured by a GFP-reporter assay. Depletion of c-Myc was found to be correlated with reduced expression levels of BRCA1 mRNA and BRCA1 protein. Depletion of c-Myc decreased BRCA1 promoter activity, while ectopically expressed c-Myc increased BRCA1 promoter activity. In the distal BRCA1 promoter, DNA sequence analysis revealed two tandem clusters with high similarity, and each cluster contained a possible c-Myc binding site. c-Myc bound to these regions in vivo. Nucleotide substitutions in the c-Myc binding sites in these regions abrogated c-Myc-dependent promoter activation. Furthermore, breast cancer cells with reduced BRCA1 expression due to depletion of c-Myc exhibited impaired DNA repair activity. The distal BRCA1 promoter region is associated with c

Star Formation Activity in CLASH Brightest Cluster Galaxies

Science.gov (United States)

Fogarty, Kevin; Postman, Marc; Connor, Thomas; Donahue, Megan; Moustakas, John

2015-11-01

The CLASH X-ray selected sample of 20 galaxy clusters contains 10 brightest cluster galaxies (BCGs) that exhibit significant (>5σ) extinction-corrected star formation rates (SFRs). Star formation activity is inferred from photometric estimates of UV and Hα+[N ii] emission in knots and filaments detected in CLASH Hubble Space Telescope ACS and WFC3 observations. UV-derived SFRs in these BCGs span two orders of magnitude, including two with a SFR ≳ 100 M⊙ yr-1. These measurements are supplemented with [O ii], [O iii], and Hβ fluxes measured from spectra obtained with the SOAR telescope. We confirm that photoionization from ongoing star formation powers the line emission nebulae in these BCGs, although in many BCGs there is also evidence of a LINER-like contribution to the line emission. Coupling these data with Chandra X-ray measurements, we infer that the star formation occurs exclusively in low-entropy cluster cores and exhibits a correlation with gas properties related to cooling. We also perform an in-depth study of the starburst history of the BCG in the cluster RXJ1532.9+3021, and create 2D maps of stellar properties on scales down to ˜350 pc. These maps reveal evidence for an ongoing burst occurring in elongated filaments, generally on ˜0.5-1.0 Gyr timescales, although some filaments are consistent with much younger (≲100 Myr) burst timescales and may be correlated with recent activity from the active galactic nucleus. The relationship between BCG SFRs and the surrounding intracluster medium gas properties provide new support for the process of feedback-regulated cooling in galaxy clusters and is consistent with recent theoretical predictions. Based on observations obtained at the Southern Astrophysical Research (SOAR) telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the U.S. National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel

Bayesian versus frequentist statistical inference for investigating a one-off cancer cluster reported to a health department

Directory of Open Access Journals (Sweden)

Wills Rachael A

2009-05-01

Full Text Available Abstract Background The problem of silent multiple comparisons is one of the most difficult statistical problems faced by scientists. It is a particular problem for investigating a one-off cancer cluster reported to a health department because any one of hundreds, or possibly thousands, of neighbourhoods, schools, or workplaces could have reported a cluster, which could have been for any one of several types of cancer or any one of several time periods. Methods This paper contrasts the frequentist approach with a Bayesian approach for dealing with silent multiple comparisons in the context of a one-off cluster reported to a health department. Two published cluster investigations were re-analysed using the Dunn-Sidak method to adjust frequentist p-values and confidence intervals for silent multiple comparisons. Bayesian methods were based on the Gamma distribution. Results Bayesian analysis with non-informative priors produced results similar to the frequentist analysis, and suggested that both clusters represented a statistical excess. In the frequentist framework, the statistical significance of both clusters was extremely sensitive to the number of silent multiple comparisons, which can only ever be a subjective "guesstimate". The Bayesian approach is also subjective: whether there is an apparent statistical excess depends on the specified prior. Conclusion In cluster investigations, the frequentist approach is just as subjective as the Bayesian approach, but the Bayesian approach is less ambitious in that it treats the analysis as a synthesis of data and personal judgements (possibly poor ones, rather than objective reality. Bayesian analysis is (arguably a useful tool to support complicated decision-making, because it makes the uncertainty associated with silent multiple comparisons explicit.

Attenuation of eph receptor kinase activation in cancer cells by coexpressed ephrin ligands.

Directory of Open Access Journals (Sweden)

Giulia Falivelli

Full Text Available The Eph receptor tyrosine kinases mediate juxtacrine signals by interacting "in trans" with ligands anchored to the surface of neighboring cells via a GPI-anchor (ephrin-As or a transmembrane segment (ephrin-Bs, which leads to receptor clustering and increased kinase activity. Additionally, soluble forms of the ephrin-A ligands released from the cell surface by matrix metalloproteases can also activate EphA receptor signaling. Besides these trans interactions, recent studies have revealed that Eph receptors and ephrins coexpressed in neurons can also engage in lateral "cis" associations that attenuate receptor activation by ephrins in trans with critical functional consequences. Despite the importance of the Eph/ephrin system in tumorigenesis, Eph receptor-ephrin cis interactions have not been previously investigated in cancer cells. Here we show that in cancer cells, coexpressed ephrin-A3 can inhibit the ability of EphA2 and EphA3 to bind ephrins in trans and become activated, while ephrin-B2 can inhibit not only EphB4 but also EphA3. The cis inhibition of EphA3 by ephrin-B2 implies that in some cases ephrins that cannot activate a particular Eph receptor in trans can nevertheless inhibit its signaling ability through cis association. We also found that an EphA3 mutation identified in lung cancer enhances cis interaction with ephrin-A3. These results suggest a novel mechanism that may contribute to cancer pathogenesis by attenuating the tumor suppressing effects of Eph receptor signaling pathways activated by ephrins in trans.

Glycogen synthase kinase 3 beta inhibits microRNA-183-96-182 cluster via the β-Catenin/TCF/LEF-1 pathway in gastric cancer cells.

Science.gov (United States)

Tang, Xiaoli; Zheng, Dong; Hu, Ping; Zeng, Zongyue; Li, Ming; Tucker, Lynne; Monahan, Renee; Resnick, Murray B; Liu, Manran; Ramratnam, Bharat

2014-03-01

Glycogen synthase kinase 3 beta (GSK3β) is a critical protein kinase that phosphorylates numerous proteins in cells and thereby impacts multiple pathways including the β-Catenin/TCF/LEF-1 pathway. MicroRNAs (miRs) are a class of noncoding small RNAs of ∼22 nucleotides in length. Both GSK3β and miR play myriad roles in cell functions including stem cell development, apoptosis, embryogenesis and tumorigenesis. Here we show that GSK3β inhibits the expression of miR-96, miR-182 and miR-183 through the β-Catenin/TCF/LEF-1 pathway. Knockout of GSK3β in mouse embryonic fibroblast cells increases expression of miR-96, miR-182 and miR-183, coinciding with increases in the protein level and nuclear translocation of β-Catenin. In addition, overexpression of β-Catenin enhances the expression of miR-96, miR-182 and miR-183 in human gastric cancer AGS cells. GSK3β protein levels are decreased in human gastric cancer tissue compared with surrounding normal gastric tissue, coinciding with increases of β-Catenin protein, miR-96, miR-182, miR-183 and primary miR-183-96-182 cluster (pri-miR-183). Furthermore, suppression of miR-183-96-182 cluster with miRCURY LNA miR inhibitors decreases the proliferation and migration of AGS cells. Knockdown of GSK3β with siRNA increases the proliferation of AGS cells. Mechanistically, we show that β-Catenin/TCF/LEF-1 binds to the promoter of miR-183-96-182 cluster gene and thereby activates the transcription of the cluster. In summary, our findings identify a novel role for GSK3β in the regulation of miR-183-96-182 biogenesis through β-Catenin/TCF/LEF-1 pathway in gastric cancer cells.

A THREE-STEP SPATIAL-TEMPORAL-SEMANTIC CLUSTERING METHOD FOR HUMAN ACTIVITY PATTERN ANALYSIS

Directory of Open Access Journals (Sweden)

W. Huang

2016-06-01

Full Text Available How people move in cities and what they do in various locations at different times form human activity patterns. Human activity pattern plays a key role in in urban planning, traffic forecasting, public health and safety, emergency response, friend recommendation, and so on. Therefore, scholars from different fields, such as social science, geography, transportation, physics and computer science, have made great efforts in modelling and analysing human activity patterns or human mobility patterns. One of the essential tasks in such studies is to find the locations or places where individuals stay to perform some kind of activities before further activity pattern analysis. In the era of Big Data, the emerging of social media along with wearable devices enables human activity data to be collected more easily and efficiently. Furthermore, the dimension of the accessible human activity data has been extended from two to three (space or space-time to four dimensions (space, time and semantics. More specifically, not only a location and time that people stay and spend are collected, but also what people “say” for in a location at a time can be obtained. The characteristics of these datasets shed new light on the analysis of human mobility, where some of new methodologies should be accordingly developed to handle them. Traditional methods such as neural networks, statistics and clustering have been applied to study human activity patterns using geosocial media data. Among them, clustering methods have been widely used to analyse spatiotemporal patterns. However, to our best knowledge, few of clustering algorithms are specifically developed for handling the datasets that contain spatial, temporal and semantic aspects all together. In this work, we propose a three-step human activity clustering method based on space, time and semantics to fill this gap. One-year Twitter data, posted in Toronto, Canada, is used to test the clustering-based method. The

Telomerase activity in gastric cancer.

Science.gov (United States)

Hiyama, E; Yokoyama, T; Tatsumoto, N; Hiyama, K; Imamura, Y; Murakami, Y; Kodama, T; Piatyszek, M A; Shay, J W; Matsuura, Y

1995-08-01

Although many genetic alterations have been reported in gastric cancer, it is not known whether all gastric tumors are capable of indefinite proliferative potential, e.g., immortality. The expression of telomerase and stabilization of telomeres are concomitant with the attainment of immortality in tumor cells; thus, the measurement of telomerase activity in clinically obtained tumor samples may provide important information useful both as a diagnostic marker to detect immortal cancer cells in clinical materials and as a prognostic indicator of patient outcome. Telomerase activity was analyzed in 66 primary gastric cancers with the use of a PCR-based assay. The majority of tumors (85%) displayed telomerase activity, but telomerase was undetectable in 10 tumors (15%), 8 of which were early stage tumors. Most of the tumors with telomerase activity were large and of advanced stages, including metastases. Survival rate of patients of tumors with detectable telomerase activity was significantly shorter than that of those without telomerase activity. Alterations of telomere length (reduced/elongated terminal restriction fragments) were detected in 14 of 66 (21%) gastric cancers, and all 14 had telomerase activity. Cellular DNA contents revealed that all 22 aneuploid tumors had detectable telomerase activity. The present results indicate that telomerase activation may be required as a critical step in the multigenetic process of tumorigenesis, and that telomerase is frequently but not always activated as a late event in gastric cancer progression.

Chandra Finds Surprising Black Hole Activity In Galaxy Cluster

Science.gov (United States)

2002-09-01

Scientists at the Carnegie Observatories in Pasadena, California, have uncovered six times the expected number of active, supermassive black holes in a single viewing of a cluster of galaxies, a finding that has profound implications for theories as to how old galaxies fuel the growth of their central black holes. The finding suggests that voracious, central black holes might be as common in old, red galaxies as they are in younger, blue galaxies, a surprise to many astronomers. The team made this discovery with NASA'S Chandra X-ray Observatory. They also used Carnegie's 6.5-meter Walter Baade Telescope at the Las Campanas Observatory in Chile for follow-up optical observations. "This changes our view of galaxy clusters as the retirement homes for old and quiet black holes," said Dr. Paul Martini, lead author on a paper describing the results that appears in the September 10 issue of The Astrophysical Journal Letters. "The question now is, how do these black holes produce bright X-ray sources, similar to what we see from much younger galaxies?" Typical of the black hole phenomenon, the cores of these active galaxies are luminous in X-ray radiation. Yet, they are obscured, and thus essentially undetectable in the radio, infrared and optical wavebands. "X rays can penetrate obscuring gas and dust as easily as they penetrate the soft tissue of the human body to look for broken bones," said co-author Dr. Dan Kelson. "So, with Chandra, we can peer through the dust and we have found that even ancient galaxies with 10-billion-year-old stars can have central black holes still actively pulling in copious amounts of interstellar gas. This activity has simply been hidden from us all this time. This means these galaxies aren't over the hill after all and our theories need to be revised." Scientists say that supermassive black holes -- having the mass of millions to billions of suns squeezed into a region about the size of our Solar System -- are the engines in the cores of

The development of innovation activities clusters in Russia and in the Czech Republic

Directory of Open Access Journals (Sweden)

Alexey Lesnik

2013-09-01

Full Text Available Innovative development becomes the main tendency of the modern world economy. The paper presents a comparative analysis of the development of Russian and Czech clusters engaged in innovation activities. Innovative cluster is one of the most effective forms for reaching a high level of competitiveness. Development of the cluster as a new form of managing, economic interaction and connections allows to reach social and economic effect. The whole point of the innovative cluster is that the enterprises and the organizations merge with each other and create a new product or service and put means in development. Cooperation between companies allows toreduce costs for its development and researches with the commercialization of the new good or service in the future. The activity of the cluster has a constructive nature, which consists in the majority of participants of innovative cluster do not compete among themselves; they work for the common objective. Innovative clusters exist not only in the developed countries, but also in the developing states. Innovative activity in the developed countries arose earlier and began to form rapider. The innovative clusters have promoted the development of the European countries. Domination of the clusters in the economy is significant both for national, and for a regional economy, where high geographical concentration of the interconnected industries is observed. The cluster approach gives the effective tool for the achievement of main goals: increase of the level of profitableness of the region and employment of the population, promotes strengthening of the competitive advantages of separate companies and all economy as a whole.

Progress on clustered DNA damage in radiation research

International Nuclear Information System (INIS)

Yang Li'na; Zhang Hong; Di Cuixia; Zhang Qiuning; Wang Xiaohu

2012-01-01

Clustered DNA damage which caused by high LET heavy ion radiation can lead to mutation, tumorigenesis and apoptosis. Promoting apoptosis of cancer cells is always the basis of cancer treatment. Clustered DNA damage has been the hot topic in radiobiology. The detect method is diversity, but there is not a detail and complete protocol to analyze clustered DNA damage. In order to provide reference for clustered DNA damage in the radiotherapy study, the clustered DNA damage characteristics, the latest progresses on clustered DNA damage and the detecting methods are reviewed and discussed in detail in this paper. (authors)

Micro-flock patterns and macro-clusters in chiral active Brownian disks

Science.gov (United States)

Levis, Demian; Liebchen, Benno

2018-02-01

Chiral active particles (or self-propelled circle swimmers) feature a rich collective behavior, comprising rotating macro-clusters and micro-flock patterns which consist of phase-synchronized rotating clusters with a characteristic self-limited size. These patterns emerge from the competition of alignment interactions and rotations suggesting that they might occur generically in many chiral active matter systems. However, although excluded volume interactions occur naturally among typical circle swimmers, it is not yet clear if macro-clusters and micro-flock patterns survive their presence. The present work shows that both types of pattern do survive but feature strongly enhance fluctuations regarding the size and shape of the individual clusters. Despite these fluctuations, we find that the average micro-flock size still follows the same characteristic scaling law as in the absence of excluded volume interactions, i.e. micro-flock sizes scale linearly with the single-swimmer radius.

Substructure in clusters of galaxies

International Nuclear Information System (INIS)

Fitchett, M.J.

1988-01-01

Optical observations suggesting the existence of substructure in clusters of galaxies are examined. Models of cluster formation and methods used to detect substructure in clusters are reviewed. Consideration is given to classification schemes based on a departure of bright cluster galaxies from a spherically symmetric distribution, evidence for statistically significant substructure, and various types of substructure, including velocity, spatial, and spatial-velocity substructure. The substructure observed in the galaxy distribution in clusters is discussed, focusing on observations from general cluster samples, the Virgo cluster, the Hydra cluster, Centaurus, the Coma cluster, and the Cancer cluster. 88 refs

Residential cancer cluster investigation nearby a Superfund Study Area with trichloroethylene contamination.

Science.gov (United States)

Press, David J; McKinley, Meg; Deapen, Dennis; Clarke, Christina A; Gomez, Scarlett Lin

2016-05-01

Trichloroethylene (TCE) is an industrial solvent associated with liver cancer, kidney cancer, and non-Hodgkin's lymphoma (NHL). It is unclear whether an excess of TCE-associated cancers have occurred surrounding the Middlefield-Ellis-Whisman Superfund site in Mountain View, California. We conducted a population-based cancer cluster investigation comparing the incidence of NHL, liver, and kidney cancers in the neighborhood of interest to the incidence among residents in the surrounding four-county region. Case counts and address information were obtained using routinely collected data from the Greater Bay Area Cancer Registry, part of the Surveillance, Epidemiology, and End Results program. Population denominators were obtained from the 1990, 2000, and 2010 US censuses. Standardized incidence ratios (SIRs) with two-sided 99 % confidence intervals (CIs) were calculated for time intervals surrounding the US Censuses. There were no statistically significant differences between the neighborhood of interest and the larger region for cancers of the liver or kidney. A statistically significant elevation was observed for NHL during one of the three time periods evaluated (1996-2005: SIR = 1.8, 99 % CI 1.1-2.8). No statistically significant NHL elevation existed in the earlier 1988-1995 (SIR = 1.3, 99 % CI 0.5-2.6) or later 2006-2011 (SIR = 1.3, 99 % CI 0.6-2.4) periods. There is no evidence of an increased incidence of liver or kidney cancer, and there is a lack of evidence of a consistent, sustained, or more recent elevation in NHL occurrence in this neighborhood. This evaluation included existing cancer registry data, which cannot speak to specific exposures incurred by past or current residents of this neighborhood.

Evaluation of Modified Categorical Data Fuzzy Clustering Algorithm on the Wisconsin Breast Cancer Dataset

Directory of Open Access Journals (Sweden)

Amir Ahmad

2016-01-01

Full Text Available The early diagnosis of breast cancer is an important step in a fight against the disease. Machine learning techniques have shown promise in improving our understanding of the disease. As medical datasets consist of data points which cannot be precisely assigned to a class, fuzzy methods have been useful for studying of these datasets. Sometimes breast cancer datasets are described by categorical features. Many fuzzy clustering algorithms have been developed for categorical datasets. However, in most of these methods Hamming distance is used to define the distance between the two categorical feature values. In this paper, we use a probabilistic distance measure for the distance computation among a pair of categorical feature values. Experiments demonstrate that the distance measure performs better than Hamming distance for Wisconsin breast cancer data.

Sensitivity evaluation of dynamic speckle activity measurements using clustering methods

International Nuclear Information System (INIS)

Etchepareborda, Pablo; Federico, Alejandro; Kaufmann, Guillermo H.

2010-01-01

We evaluate and compare the use of competitive neural networks, self-organizing maps, the expectation-maximization algorithm, K-means, and fuzzy C-means techniques as partitional clustering methods, when the sensitivity of the activity measurement of dynamic speckle images needs to be improved. The temporal history of the acquired intensity generated by each pixel is analyzed in a wavelet decomposition framework, and it is shown that the mean energy of its corresponding wavelet coefficients provides a suited feature space for clustering purposes. The sensitivity obtained by using the evaluated clustering techniques is also compared with the well-known methods of Konishi-Fujii, weighted generalized differences, and wavelet entropy. The performance of the partitional clustering approach is evaluated using simulated dynamic speckle patterns and also experimental data.

Fischer–Tropsch Synthesis at a Low Pressure on Subnanometer Cobalt Oxide Clusters: The Effect of Cluster Size and Support on Activity and Selectivity

Energy Technology Data Exchange (ETDEWEB)

Lee, Sungsik; Lee, Byeongdu; Seifert, Sönke; Winans, Randall E.; Vajda, Stefan

2015-05-21

In this study, the catalytic activity and changes in the oxidation state during the Fischer Tropsch (FT) reaction was investigated on subnanometer size-selected cobalt clusters deposited on oxide (Al2O3, MgO) and carbon-based (ultrananocrystalline diamond UNCD) supports by temperature programmed reaction (TPRx) combined with in-situ grazing-incidence X-ray absorption characterization (GIXAS). The activity and selectivity of ultrasmall cobalt clusters exhibits a very strong dependence on cluster size and support. The evolution of the oxidation state of metal cluster during the reaction reveals that metal-support interaction plays a key role in the reaction.

The WHISPER Relaxation Sounder and the CLUSTER Active Archive

Science.gov (United States)

Trotignon, J. G.; Décréau, P. M. E.; Rauch, J. L.; Vallières, X.; Rochel, A.; Kougblénou, S.; Lointier, G.; Facskó, G.; Canu, P.; Darrouzet, F.; Masson, A.

The Waves of HIgh frequency and Sounder for Probing of Electron density by Relaxation (WHISPER) instrument is part of the Wave Experiment Consortium (WEC) of the CLUSTER mission. With the help of the long double sphere antennae of the Electric Field and Wave (EFW) instrument and the Digital Wave Processor (DWP), it delivers active (sounding) and natural (transmitter off) electric field spectra, respectively from 4 to 82 kHz, and from 2 to 80 kHz. These frequency ranges have been chosen to include the electron plasma frequency, which is closely related to the total electron density, in most of the regions encountered by the CLUSTER spacecraft. Presented here is an overview of the WHISPER data products available in the CLUSTER Active Archive (CAA). The instrument and its performance are first recalled. The way the WHISPER products are obtained is then described, with particular attention being paid to the density determination. Both sounding and natural measurements are commonly used in this process, which depends on the ambient plasma regime. This is illustrated using drawings similar to the Bryant plots commonly used in the CLUSTER master science plan. These give a clear overview of typical density values and the parts of the orbits where they are obtained. More information on the applied software or on the quality/reliability of the density determination can also be highlighted.

Impact of a cancer clinical trials web site on discussions about trial participation: a cluster randomized trial.

Science.gov (United States)

Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N

2012-07-01

Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.

Tumor-Promoting Circuits That Regulate a Cancer-Related Chemokine Cluster: Dominance of Inflammatory Mediators Over Oncogenic Alterations

International Nuclear Information System (INIS)

Leibovich-Rivkin, Tal; Buganim, Yosef; Solomon, Hilla; Meshel, Tsipi; Rotter, Varda; Ben-Baruch, Adit

2012-01-01

Here, we investigated the relative contribution of genetic/signaling components versus microenvironmental factors to the malignancy phenotype. In this system, we took advantage of non-transformed fibroblasts that carried defined oncogenic modifications in Ras and/or p53. These cells were exposed to microenvironmental pressures, and the expression of a cancer-related chemokine cluster was used as readout for the malignancy potential (CCL2, CCL5, CXCL8, CXCL10). In cells kept in-culture, synergism between Ras hyper-activation and p53 dysfunction was required to up-regulate the expression of the chemokine cluster. The in vivo passage of Ras High /p53 Low -modified cells has led to tumor formation, accompanied by potentiation of chemokine release, implicating a powerful role for the tumor microenvironment in up-regulating the chemokine cluster. Indeed, we found that inflammatory mediators which are prevalent in tumor sites, such as TNFα and IL-1β, had a predominant impact on the release of the chemokines, which was substantially higher than that obtained by the oncogenic modifications alone, possibly acting through the transcription factors AP-1 and NF-κB. Together, our results propose that in the unbiased model system that we were using, inflammatory mediators of the tumor milieu have dominating roles over oncogenic modifications in dictating the expression of a pro-malignancy chemokine readout

Clustering and phase behaviour of attractive active particles with hydrodynamics.

Science.gov (United States)

Navarro, Ricard Matas; Fielding, Suzanne M

2015-10-14

We simulate clustering, phase separation and hexatic ordering in a monolayered suspension of active squirming disks subject to an attractive Lennard-Jones-like pairwise interaction potential, taking hydrodynamic interactions between the particles fully into account. By comparing the hydrodynamic case with counterpart simulations for passive and active Brownian particles, we elucidate the relative roles of self-propulsion, interparticle attraction, and hydrodynamic interactions in determining clustering and phase behaviour. Even in the presence of an attractive potential, we find that hydrodynamic interactions strongly suppress the motility induced phase separation that might a priori have been expected in a highly active suspension. Instead, we find only a weak tendency for the particles to form stringlike clusters in this regime. At lower activities we demonstrate phase behaviour that is broadly equivalent to that of the counterpart passive system at low temperatures, characterized by regimes of gas-liquid, gas-solid and liquid-solid phase coexistence. In this way, we suggest that a dimensionless quantity representing the level of activity relative to the strength of attraction plays the role of something like an effective non-equilibrium temperature, counterpart to the (dimensionless) true thermodynamic temperature in the passive system. However there are also some important differences from the equilibrium case, most notably with regards the degree of hexatic ordering, which we discuss carefully.

Dual activation of pathways regulated by steroid receptors and peptide growth factors in primary prostate cancer revealed by Factor Analysis of microarray data

Directory of Open Access Journals (Sweden)

Fernandez Pedro L

2005-08-01

Full Text Available Abstract Background We use an approach based on Factor Analysis to analyze datasets generated for transcriptional profiling. The method groups samples into biologically relevant categories, and enables the identification of genes and pathways most significantly associated to each phenotypic group, while allowing for the participation of a given gene in more than one cluster. Genes assigned to each cluster are used for the detection of pathways predominantly activated in that cluster by finding statistically significant associated GO terms. We tested the approach with a published dataset of microarray experiments in yeast. Upon validation with the yeast dataset, we applied the technique to a prostate cancer dataset. Results Two major pathways are shown to be activated in organ-confined, non-metastatic prostate cancer: those regulated by the androgen receptor and by receptor tyrosine kinases. A number of gene markers (HER3, IQGAP2 and POR1 highlighted by the software and related to the later pathway have been validated experimentally a posteriori on independent samples. Conclusion Using a new microarray analysis tool followed by a posteriori experimental validation of the results, we have confirmed several putative markers of malignancy associated with peptide growth factor signalling in prostate cancer and revealed others, most notably ERRB3 (HER3. Our study suggest that, in primary prostate cancer, HER3, together or not with HER4, rather than in receptor complexes involving HER2, could play an important role in the biology of these tumors. These results provide new evidence for the role of receptor tyrosine kinases in the establishment and progression of prostate cancer.

ENTREPRENEURIAL ACTIVITY IN ROMANIA – A TIME SERIES CLUSTERING ANALYSIS AT THE NUTS3 LEVEL

Directory of Open Access Journals (Sweden)

Sipos-Gug Sebastian

2013-07-01

Full Text Available Entrepreneurship is an active field of research, having known a major increase in interest and publication levels in the last years (Landström et al., 2012. Within this field recently there has been an increasing interest in understanding why some regions seem to have a significantly higher entrepreneurship activity compared to others. In line with this research field, we would like to investigate the differences in entrepreneurial activity among the Romanian counties (NUTS 3 regions. While the classical research paradigm in this field is to conduct a temporally stationary analysis, we choose to use a time series clustering analysis to better understanding the dynamics of entrepreneurial activity between counties. Our analysis showed that if we use the total number of new privately owned companies that are founded each year in the last decade (2002-2012 we can distinguish between 5 clusters, one with high total entrepreneurial activity (18 counties, one with above average activity (8 counties, two clusters with average and slightly below average activity (total of 18 counties and one cluster with low and declining activity (2 counties. If we are interested in the entrepreneurial activity rate, that is the number of new privately owned companies founded each year adjusted by the population of the respective county, we obtain 4 clusters, one with a very high entrepreneurial rate (1 county, one with average rate (10 counties, and two clusters with below average entrepreneurial rate (total of 31 counties. In conclusion, our research shows that Romania is far from being a homogeneous geographical area in respect to entrepreneurial activity. Depending on what we are interested in, it can be divided in 5 or 4 clusters of counties, which behave differently as a function of time. Further research should be focused on explaining these regional differences, on studying the high performance clusters and trying to improve the low performing ones.

Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

Directory of Open Access Journals (Sweden)

Chi H.J. Kao

2013-02-01

Full Text Available ABSTRACTGanoderma lucidum, commonly referred to as Lingzhi, has been used in Asia for health promotion for centuries. The anti-cancer effects of G. lucidum have been demonstrated in both in vitro and in vivo studies. In addition, the observed anti-cancer activities of Ganoderma have prompted its usage by cancer patients alongside chemotherapy.The main two bioactive components of G. lucidum can be broadly grouped into triterpenes and polysaccharides. Despite triterpenes and polysaccharides being widely known as the major active ingredients, the different biological pathways by which they exert their anti-cancer effect remain poorly defined. Therefore, understanding the mechanisms of action may lead to more widespread use of Ganoderma as an anti-cancer agent.The aim of this paper is to summarise the various bioactive mechanisms that have been proposed for the anti-cancer properties of triterpenes and polysaccharides extracted from G. lucidum. A literature search of published papers on NCBI with keywords “Ganoderma” and “cancer” was performed. Among those, studies which specifically examined the anti-cancer activities of Ganoderma triterpenes and polysaccharides were selected to be included in this paper.We have found five potential mechanisms which are associated with the anti-cancer activities of Ganoderma triterpenes and three potential mechanisms for Ganoderma polysaccharides. In addition, G. lucidum has been used in combination with known anti-cancer agents to improve the anti-cancer efficacies. This suggests Ganoderma’s bioactive pathways may compliment that of anti-cancer agents. In this paper we present several potential anti-cancer mechanisms of Ganoderma triterpenes and polysaccharides which can be used for the development of Ganoderma as an anti-cancer agent.

Towards Clustering of Mobile and Smartwatch Accelerometer Data for Physical Activity Recognition

Directory of Open Access Journals (Sweden)

Chelsea Dobbins

2018-06-01

Full Text Available Mobile and wearable devices now have a greater capability of sensing human activity ubiquitously and unobtrusively through advancements in miniaturization and sensing abilities. However, outstanding issues remain around the energy restrictions of these devices when processing large sets of data. This paper presents our approach that uses feature selection to refine the clustering of accelerometer data to detect physical activity. This also has a positive effect on the computational burden that is associated with processing large sets of data, as energy efficiency and resource use is decreased because less data is processed by the clustering algorithms. Raw accelerometer data, obtained from smartphones and smartwatches, have been preprocessed to extract both time and frequency domain features. Principle component analysis feature selection (PCAFS and correlation feature selection (CFS have been used to remove redundant features. The reduced feature sets have then been evaluated against three widely used clustering algorithms, including hierarchical clustering analysis (HCA, k-means, and density-based spatial clustering of applications with noise (DBSCAN. Using the reduced feature sets resulted in improved separability, reduced uncertainty, and improved efficiency compared with the baseline, which utilized all features. Overall, the CFS approach in conjunction with HCA produced higher Dunn Index results of 9.7001 for the phone and 5.1438 for the watch features, which is an improvement over the baseline. The results of this comparative study of feature selection and clustering, with the specific algorithms used, has not been performed previously and provides an optimistic and usable approach to recognize activities using either a smartphone or smartwatch.

Mismatch of Posttraumatic Stress Disorder (PTSD) Symptoms and DSM-IV Symptom Clusters in a Cancer Sample: Exploratory Factor Analysis of the PTSD Checklist-Civilian Version

Science.gov (United States)

Shelby, Rebecca A.; Golden-Kreutz, Deanna M.; Andersen, Barbara L.

2007-01-01

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association, 1994a) conceptualization of posttraumatic stress disorder (PTSD) includes three symptom clusters: reexperiencing, avoidance/numbing, and arousal. The PTSD Checklist-Civilian Version (PCL-C) corresponds to the DSM-IV PTSD symptoms. In the current study, we conducted exploratory factor analysis (EFA) of the PCL-C with two aims: (a) to examine whether the PCL-C evidenced the three-factor solution implied by the DSM-IV symptom clusters, and (b) to identify a factor solution for the PCL-C in a cancer sample. Women (N = 148) with Stage II or III breast cancer completed the PCL-C after completion of cancer treatment. We extracted two-, three-, four-, and five-factor solutions using EFA. Our data did not support the DSM-IV PTSD symptom clusters. Instead, EFA identified a four-factor solution including reexperiencing, avoidance, numbing, and arousal factors. Four symptom items, which may be confounded with illness and cancer treatment-related symptoms, exhibited poor factor loadings. Using these symptom items in cancer samples may lead to overdiagnosis of PTSD and inflated rates of PTSD symptoms. PMID:16281232

A critical assessment of geographic clusters of breast and lung cancer incidences among residents living near the Tittabawassee and Saginaw Rivers, Michigan, USA.

Science.gov (United States)

Guajardo, Olga A; Oyana, Tonny J

2009-01-01

To assess previously determined geographic clusters of breast and lung cancer incidences among residents living near the Tittabawassee and Saginaw Rivers, Michigan, using a new set of environmental factors. Breast and lung cancer data were acquired from the Michigan Department of Community Health, along with point source pollution data from the U.S. Environmental Protection Agency. The datasets were used to determine whether there is a spatial association between disease risk and environmental contamination. GIS and spatial techniques were combined with statistical analysis to investigate local risk of breast and lung cancer. The study suggests that neighborhoods in close proximity to the river were associated with a high risk of breast cancer, while increased risk of lung cancer was detected among neighborhoods in close proximity to point source pollution and major highways. Statistically significant (P clusters of cancer incidences were observed among residents living near the rivers. These findings are useful to researchers and governmental agencies for risk assessment, regulation, and control of environmental contamination in the floodplains.

A Critical Assessment of Geographic Clusters of Breast and Lung Cancer Incidences among Residents Living near the Tittabawassee and Saginaw Rivers, Michigan, USA

Directory of Open Access Journals (Sweden)

Olga A. Guajardo

2009-01-01

Full Text Available Objectives. To assess previously determined geographic clusters of breast and lung cancer incidences among residents living near the Tittabawassee and Saginaw Rivers, Michigan, using a new set of environmental factors. Materials and Methods. Breast and lung cancer data were acquired from the Michigan Department of Community Health, along with point source pollution data from the U.S. Environmental Protection Agency. The datasets were used to determine whether there is a spatial association between disease risk and environmental contamination. GIS and spatial techniques were combined with statistical analysis to investigate local risk of breast and lung cancer. Results and Conclusion. The study suggests that neighborhoods in close proximity to the river were associated with a high risk of breast cancer, while increased risk of lung cancer was detected among neighborhoods in close proximity to point source pollution and major highways. Statistically significant (P≤.001 clusters of cancer incidences were observed among residents living near the rivers. These findings are useful to researchers and governmental agencies for risk assessment, regulation, and control of environmental contamination in the floodplains.

A Critical Assessment of Geographic Clusters of Breast and Lung Cancer Incidences among Residents Living near the Tittabawassee and Saginaw Rivers, Michigan, USA

International Nuclear Information System (INIS)

Guajardo, O.A.; Oyana, T.J.

2010-01-01

Objectives. To assess previously determined geographic clusters of breast and lung cancer incidences among residents living near the Tittabawassee and Saginaw Rivers, Michigan, using a new set of environmental factors. Materials and Methods. Breast and lung cancer data were acquired from the Michigan Department of Community Health, along with point source pollution data from the U.S. Environmental Protection Agency. The datasets were used to determine whether there is a spatial association between disease risk and environmental contamination. GIS and spatial techniques were combined with statistical analysis to investigate local risk of breast and lung cancer. Results and Conclusion. The study suggests that neighborhoods in close proximity to the river were associated with a high risk of breast cancer, while increased risk of lung cancer was detected among neighborhoods in close proximity to point source pollution and major highways. Statistically significant (P=.001) clusters of cancer incidences were observed among residents living near the rivers. These findings are useful to researchers and governmental agencies for risk assessment, regulation, and control of environmental contamination in the flood plains.

Regulation of ROCK Activity in Cancer

DEFF Research Database (Denmark)

Morgan-Fisher, Marie; Wewer, Ulla M; Yoneda, Atsuko

2013-01-01

, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer.......Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key...... regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active...

Variations in 137Cs activity concentrations in individual fruitbodies in clusters of Cantharellus tubaeformis

International Nuclear Information System (INIS)

Nikolova, I.; Johanson, K.J.

1999-01-01

Fruitbodies of Cantharellus tubaeformis grown in clusters were collected from a normal Swedish coniferous forest. In the laboratory, individual fruitbodies were transferred into plastic vials and the 137 Cs activity concentrations were determined and expressed as Bq kg -1 fresh weight. After drying at 55 o , the 137 CS levels were recalculated and expressed as Bq kg -1 dry weight. Large variations of 137 Cs activity concentrations between individual fruitbodies within the clusters were observed. In 1995, the range in the 137 CS levels of individual fruitbodies in one cluster were from 9,194 to 164,811 and in another cluster from 2,338 to 38,377 Bq kg -1 . The mean values for these two clusters were 90,294 and 13,556 Bq kg -1 respectively. In 1998, the mean value for eight clusters showed a range from 26,373 to 67,281 Bq kg -1 . The largest variations between individual fruitbodies within a cluster were from 11,875 to 107,160 Bq kg -1 . Refs. 10 (author)

Mechanisms of transcriptional regulation and prognostic significance of activated leukocyte cell adhesion molecule in cancer

Directory of Open Access Journals (Sweden)

Chen Hairu

2010-10-01

Full Text Available Abstract Background Activated leukocyte cell adhesion molecule (ALCAM is implicated in the prognosis of multiple cancers with low level expression associated with metastasis and early death in breast cancer. Despite this significance, mechanisms that regulate ALCAM gene expression and ALCAM's role in adhesion of pre-metastatic circulating tumor cells have not been defined. We studied ALCAM expression in 20 tumor cell lines by real-time PCR, western blot and immunochemistry. Epigenetic alterations of the ALCAM promoter were assessed using methylation-specific PCR and bisulfite sequencing. ALCAM's role in adhesion of tumor cells to the vascular wall was studied in isolated perfused lungs. Results A common site for transcription initiation of the ALCAM gene was identified and the ALCAM promoter sequenced. The promoter contains multiple cis-active elements including a functional p65 NF-κB motif, and it harbors an extensive array of CpG residues highly methylated exclusively in ALCAM-negative tumor cells. These CpG residues were modestly demethylated after 5-aza-2-deoxycytidine treatment. Restoration of high-level ALCAM expression using an ALCAM cDNA increased clustering of MDA-MB-435 tumor cells perfused through the pulmonary vasculature of ventilated rat lungs. Anti-ALCAM antibodies reduced the number of intravascular tumor cell clusters. Conclusion Our data suggests that loss of ALCAM expression, due in part to DNA methylation of extensive segments of the promoter, significantly impairs the ability of circulating tumor cells to adhere to each other, and may therefore promote metastasis. These findings offer insight into the mechanisms for down-regulation of ALCAM gene expression in tumor cells, and for the positive prognostic value of high-level ALCAM in breast cancer.

Relationship between cancer-related fatigue and physical activity in inpatient cancer rehabilitation.

Science.gov (United States)

Kummer, Franziska; Catuogno, Silvio; Perseus, Josef M; Bloch, Wilhelm; Baumann, Freerk T

2013-08-01

Fatigue is a serious problem for the majority of patients with cancer. In this context, several studies have shown benefits of physical activity during and following treatment. However, uncertainties remain regarding the optimal type and duration of physical activity. Therefore, this study examined the relationship between cancer-related fatigue and physical activity in the course of inpatient rehabilitation. Fatigue (Multidimensional Fatigue Inventory) and physical activity (Freiburg Questionnaire of Physical Activity) were assessed in a consecutive series of 35 patients with cancer attending oncological inpatient rehabilitation during a six-month study period. The three-week rehabilitation program included daily exercise therapy consisting of aerobic endurance training, moderate resistance training, coordination exercises, relaxation training and individual physiotherapy. At discharge, a significant improvement in each dimension of cancer-related fatigue (p=0.001-0.003) and a significant increase of physical activity levels (p=0.001) were observed. A small, but significant negative correlation was found between cancer-related fatigue and the level of physical activity (R=-0.438, p=0.004). The largest effects were associated with a weekly energy expenditure of 3000 kcal through physical activity. The results support a non-linear dose-response relationship between cancer-related fatigue and physical activity. Since this is the first study providing specific exercise recommendations for an effective treatment of cancer-related fatigue in the context of inpatient rehabilitation, further research is required to validate the observed trends.

The Quality Initiative in Rectal Cancer (QIRC trial: study protocol of a cluster randomized controlled trial in surgery

Directory of Open Access Journals (Sweden)

Thabane Lehana

2008-02-01

Full Text Available Abstract Background Two unfortunate outcomes for patients treated surgically for rectal cancer are placement of a permanent colostomy and local tumor recurrence. Total mesorectal excision is a new technique for rectal cancer surgery that can lead to improved patient outcomes. We describe a cluster randomized controlled trial that is testing if the above patient outcomes can be improved through a knowledge translation strategy called the Quality Initiative in Rectal Cancer (QIRC strategy. The strategy is designed to optimize the use of total mesorectal excision techniques. Methods and Design Hospitals were randomized to the QIRC strategy (experimental group versus normal practice environment (control group. Participating hospitals, and the respective surgeon group operating in them, are from Ontario, Canada and have an annual procedure volume for major rectal cancer resections of 15 or greater. Patients were eligible if they underwent major rectal surgery for a diagnosis of primary rectal cancer. The surgeon-directed QIRC interventions included a workshop, use of opinion leaders, operative demonstrations, a post-operative questionnaire, and, audit and feedback. For an operative demonstration participating surgeons invited a study team surgeon to assist them with a case of rectal cancer surgery. The intent was to demonstrate total mesorectal excision techniques. Control arm surgeons received no intervention. Sample size calculations were two-sided, considered the clustering of data at the hospital level, and were driven by requirements for the outcome local recurrence. To detect an improvement in local recurrence from 20% to 8% with confidence we required 16 hospitals and 672 patients – 8 hospitals and 336 patients in each arm. Outcomes data are collected via chart review for at least 30 months after surgery. Analyses will use an intention-to-treat principle and will consider the clustering of data. Data collection will be complete by the end of

Topic modeling for cluster analysis of large biological and medical datasets.

Science.gov (United States)

Zhao, Weizhong; Zou, Wen; Chen, James J

2014-01-01

The big data moniker is nowhere better deserved than to describe the ever-increasing prodigiousness and complexity of biological and medical datasets. New methods are needed to generate and test hypotheses, foster biological interpretation, and build validated predictors. Although multivariate techniques such as cluster analysis may allow researchers to identify groups, or clusters, of related variables, the accuracies and effectiveness of traditional clustering methods diminish for large and hyper dimensional datasets. Topic modeling is an active research field in machine learning and has been mainly used as an analytical tool to structure large textual corpora for data mining. Its ability to reduce high dimensionality to a small number of latent variables makes it suitable as a means for clustering or overcoming clustering difficulties in large biological and medical datasets. In this study, three topic model-derived clustering methods, highest probable topic assignment, feature selection and feature extraction, are proposed and tested on the cluster analysis of three large datasets: Salmonella pulsed-field gel electrophoresis (PFGE) dataset, lung cancer dataset, and breast cancer dataset, which represent various types of large biological or medical datasets. All three various methods are shown to improve the efficacy/effectiveness of clustering results on the three datasets in comparison to traditional methods. A preferable cluster analysis method emerged for each of the three datasets on the basis of replicating known biological truths. Topic modeling could be advantageously applied to the large datasets of biological or medical research. The three proposed topic model-derived clustering methods, highest probable topic assignment, feature selection and feature extraction, yield clustering improvements for the three different data types. Clusters more efficaciously represent truthful groupings and subgroupings in the data than traditional methods, suggesting

Development of Automatic Cluster Algorithm for Microcalcification in Digital Mammography

International Nuclear Information System (INIS)

Choi, Seok Yoon; Kim, Chang Soo

2009-01-01

Digital Mammography is an efficient imaging technique for the detection and diagnosis of breast pathological disorders. Six mammographic criteria such as number of cluster, number, size, extent and morphologic shape of microcalcification, and presence of mass, were reviewed and correlation with pathologic diagnosis were evaluated. It is very important to find breast cancer early when treatment can reduce deaths from breast cancer and breast incision. In screening breast cancer, mammography is typically used to view the internal organization. Clusterig microcalcifications on mammography represent an important feature of breast mass, especially that of intraductal carcinoma. Because microcalcification has high correlation with breast cancer, a cluster of a microcalcification can be very helpful for the clinical doctor to predict breast cancer. For this study, three steps of quantitative evaluation are proposed : DoG filter, adaptive thresholding, Expectation maximization. Through the proposed algorithm, each cluster in the distribution of microcalcification was able to measure the number calcification and length of cluster also can be used to automatically diagnose breast cancer as indicators of the primary diagnosis.

An integrative analysis of cellular contexts, miRNAs and mRNAs reveals network clusters associated with antiestrogen-resistant breast cancer cells

Directory of Open Access Journals (Sweden)

Nam Seungyoon

2012-12-01

Full Text Available Abstract Background A major goal of the field of systems biology is to translate genome-wide profiling data (e.g., mRNAs, miRNAs into interpretable functional networks. However, employing a systems biology approach to better understand the complexities underlying drug resistance phenotypes in cancer continues to represent a significant challenge to the field. Previously, we derived two drug-resistant breast cancer sublines (tamoxifen- and fulvestrant-resistant cell lines from the MCF7 breast cancer cell line and performed genome-wide mRNA and microRNA profiling to identify differential molecular pathways underlying acquired resistance to these important antiestrogens. In the current study, to further define molecular characteristics of acquired antiestrogen resistance we constructed an “integrative network”. We combined joint miRNA-mRNA expression profiles, cancer contexts, miRNA-target mRNA relationships, and miRNA upstream regulators. In particular, to reduce the probability of false positive connections in the network, experimentally validated, rather than prediction-oriented, databases were utilized to obtain connectivity. Also, to improve biological interpretation, cancer contexts were incorporated into the network connectivity. Results Based on the integrative network, we extracted “substructures” (network clusters representing the drug resistant states (tamoxifen- or fulvestrant-resistance cells compared to drug sensitive state (parental MCF7 cells. We identified un-described network clusters that contribute to antiestrogen resistance consisting of miR-146a, -27a, -145, -21, -155, -15a, -125b, and let-7s, in addition to the previously described miR-221/222. Conclusions By integrating miRNA-related network, gene/miRNA expression and text-mining, the current study provides a computational-based systems biology approach for further investigating the molecular mechanism underlying antiestrogen resistance in breast cancer cells. In

Plasminogen activation and cancer

DEFF Research Database (Denmark)

Danø, Keld; Behrendt, N.; Hoyer-Hansen, G.

2005-01-01

, the regulation of extracellular proteolysis in cancer involves a complex interplay between cancer cells and non-malignant stromal cells in the expression of the molecular components involved. For some types of cancer, this cellular interplay mimics that observed in the tissue of ori- gin during non......Breakdown of the extracellular matrix is crucial for cancer invasion and metastasis. It is accomplished by the concerted action of several proteases, including the serine protease plasmin and a number of matrix metalloproteases.The activity of each of these proteases is regulated by an array......-neoplastic tissue remodelling processes.We propose that cancer invasion can be considered as uncontrolled tissue remodelling. Inhibition of extracellular proteases is an attractive approach to cancer therapy. Because proteases have many different functions in the normal organism, efficient inhibition will have...

[Physical activity and cancer: Update and literature review].

Science.gov (United States)

Desnoyers, A; Riesco, E; Fülöp, T; Pavic, M

2016-06-01

Physical activity is a key determinant of public health and contributes to decreasing the prevalence of many diseases. Cancer is the leading cause of death worldwide. Physical activity, accessible to the entire population, could prevent up to 25% of cancers, in addition to improving survival rates and quality of life in cancer patients. Physical activity acts via various mechanisms to slow or decrease tumor growth, including the production and bioavailability of sex hormones, insulin resistance and insulin secretion, and inflammation. In primary prevention, physical activity reduces breast cancer risk by 15-20% and colorectal cancer risk by 24%. All-cause mortality is reduced by 33% in cancer survivors who exercise. Health-related quality of life, fatigue and depression are enhanced by the practice of physical activity in cancer patients. In the general population, the global recommendations on physical activity for health, published by the World Health Organisation, are suggested as a means of primary prevention of cancer. In cancer patients, an adapted physical activity routine is promoted from the very beginning of patient care to decrease fatigue as well as improve tolerance and benefits of treatments. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Regulation of ROCK Activity in Cancer

Science.gov (United States)

Morgan-Fisher, Marie; Wewer, Ulla M.

2013-01-01

Cancer-associated changes in cellular behavior, such as modified cell-cell contact, increased migratory potential, and generation of cellular force, all require alteration of the cytoskeleton. Two homologous mammalian serine/threonine kinases, Rho-associated protein kinases (ROCK I and II), are key regulators of the actin cytoskeleton acting downstream of the small GTPase Rho. ROCK is associated with cancer progression, and ROCK protein expression is elevated in several types of cancer. ROCKs exist in a closed, inactive conformation under quiescent conditions, which is changed to an open, active conformation by the direct binding of guanosine triphosphate (GTP)–loaded Rho. In recent years, a number of ROCK isoform-specific binding partners have been found to modulate the kinase activity through direct interactions with the catalytic domain or via altered cellular localization of the kinases. Thus, these findings demonstrate additional modes to regulate ROCK activity. This review describes the molecular mechanisms of ROCK activity regulation in cancer, with emphasis on ROCK isoform-specific regulation and interaction partners, and discusses the potential of ROCKs as therapeutic targets in cancer. PMID:23204112

Statistical analysis of activation and reaction energies with quasi-variational coupled-cluster theory

Science.gov (United States)

Black, Joshua A.; Knowles, Peter J.

2018-06-01

The performance of quasi-variational coupled-cluster (QV) theory applied to the calculation of activation and reaction energies has been investigated. A statistical analysis of results obtained for six different sets of reactions has been carried out, and the results have been compared to those from standard single-reference methods. In general, the QV methods lead to increased activation energies and larger absolute reaction energies compared to those obtained with traditional coupled-cluster theory.

Activity-induced clustering in model dumbbell swimmers: the role of hydrodynamic interactions.

Science.gov (United States)

Furukawa, Akira; Marenduzzo, Davide; Cates, Michael E

2014-08-01

Using a fluid-particle dynamics approach, we numerically study the effects of hydrodynamic interactions on the collective dynamics of active suspensions within a simple model for bacterial motility: each microorganism is modeled as a stroke-averaged dumbbell swimmer with prescribed dipolar force pairs. Using both simulations and qualitative arguments, we show that, when the separation between swimmers is comparable to their size, the swimmers' motions are strongly affected by activity-induced hydrodynamic forces. To further understand these effects, we investigate semidilute suspensions of swimmers in the presence of thermal fluctuations. A direct comparison between simulations with and without hydrodynamic interactions shows these to enhance the dynamic clustering at a relatively small volume fraction; with our chosen model the key ingredient for this clustering behavior is hydrodynamic trapping of one swimmer by another, induced by the active forces. Furthermore, the density dependence of the motility (of both the translational and rotational motions) exhibits distinctly different behaviors with and without hydrodynamic interactions; we argue that this is linked to the clustering tendency. Our study illustrates the fact that hydrodynamic interactions not only affect kinetic pathways in active suspensions, but also cause major changes in their steady state properties.

Mobile telecommunications and health: report of an investigation into an alleged cancer cluster in Sandwell, West Midlands.

Science.gov (United States)

Stewart, Antony; Rao, Jammi N; Middleton, John D; Pearmain, Philippa; Evans, Tim

2012-11-01

Residents of one street expressed concern about the number of incident cancers, following the installation of a nearby mobile phone base station. The investigation explored whether the base station could be responsible for the cancers. Data were collected from residents' medical records. GPs and oncologists provided further information. Ward-level cancer incidence and mortality data were also obtained, over four three-year time periods. A total of 19 residents had developed cancer. The collection of cancers did not fulfil the criteria for a cancer cluster. Standardized mortality ratios (SMRs) for all malignant neoplasms (excluding non-melanoma skin cancers) in females (1.38 (95% CI, 1.08-1.74)) and all persons (1.27 (CI, 1.06-1.51)) were significantly higher than in the West Midlands during 2001-3. There were no significant differences for colorectal, female breast and prostate cancers, for any time period. Standardized incidence ratios (SIRs) for non-melanoma skin cancers in males and all persons was significantly lower than in the West Midlands during 1999-2001, and significantly lower in males, females and all persons during 2002-4. We cannot conclude that the base station was responsible for the cancers. It is unlikely that information around a single base station can either demonstrate or exclude causality.

One feature of the activated southern Ordos block: the Ziwuling small earthquake cluster

Directory of Open Access Journals (Sweden)

Li Yuhang

2014-08-01

Full Text Available Small earthquakes (Ms > 2.0 have been recorded from 1970 to the present day and reveal a significant difference in seismicity between the stable Ordos block and its active surrounding area. The southern Ordos block is a conspicuous small earthquake belt clustered and isolated along the NNW direction and extends to the inner stable Ordos block; no active fault can match this small earthquake cluster. In this paper, we analyze the dynamic mechanism of this small earthquake cluster based on the GPS velocity field (from 1999 to 2007, which are mainly from Crustal Movement Observation Network of China (CMONOC with respect to the north and south China blocks. The principal direction of strain rate field, the expansion ratefield, the maximum shear strain rate, and the rotation rate were constrained using the GPS velocity field. The results show that the velocity field, which is bounded by the small earthquake cluster from Tongchuan to Weinan, differs from the strain rate field, and the crustal deformation is left-lateral shear. This left-lateral shear belt not only spatially coincides with the Neo-tectonic belt in the Weihe Basin but also with the NNW small earthquake cluster (the Ziwuling small earthquake cluster. Based on these studies, we speculate that the NNW small earthquake cluster is caused by left-lateral shear slip, which is prone to strain accumulation. When the strain releases along the weak zone of structure, small earthquakes diffuse within its upper crust. The maximum principal compression strees direction changed from NE-SW to NEE-SWW, and the former reverse faults in the southwestern margin of the Ordos block became a left-lateral strike slip due to readjustment of the tectonic strees field after the middle Pleistocene. The NNW Neo-tectonic belt in the Weihe Basin, the different movement character of the inner Weihe Basin (which was demonstrated through GPS measurements and the small earthquake cluster belt reflect the activated

miR-15a/miR-16 cluster inhibits invasion of prostate cancer cells by suppressing TGF-β signaling pathway.

Science.gov (United States)

Jin, Wei; Chen, Fangjie; Wang, Kefeng; Song, Yan; Fei, Xiang; Wu, Bin

2018-05-23

To determine whether and how miR15a/16 regulate TGF-β signaling pathways during the progression of prostate cancer. We used bioinformatics prediction, reporter gene assay, real-time PCR, Matrigel invasion assay and Western blot to dissect the molecular mechanism of how miR-15a/miR-16 may cause metastasis in prostate tumor. MiR-15a/16 targeted and inhibited the expression of endogenous Smad3 and ACVR2A proteins. The overexpression of miR15a/16 down-regulated p-smad3 expression, affected the expression of both MMP2 and E-cadherin, and down-regulated the expression of the EMT-mediated factors Snail and Twist in LNCaP prostate cancer cells. The overexpression of miR15a/16 decreased the invasion of LNCaP cells. MiR-15a/miR-16 cluster could reverse the invasion of activin A-mediated prostate cancer cells. After the inhibition of the activin/smad signaling pathway, the inhibitory effect of invasion in prostate cancer cells by miR-15a/miR-16 cluster disappeared. Our data indicated that miR15a/16 inhibited the components of TGF-β signaling pathways in LNCaP cell line, which might relate to the progression and metastasis of prostate cancer. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Objectively Measured Baseline Physical Activity Patterns in Women in the mPED Trial: Cluster Analysis.

Science.gov (United States)

Fukuoka, Yoshimi; Zhou, Mo; Vittinghoff, Eric; Haskell, William; Goldberg, Ken; Aswani, Anil

2018-02-01

Determining patterns of physical activity throughout the day could assist in developing more personalized interventions or physical activity guidelines in general and, in particular, for women who are less likely to be physically active than men. The aims of this report are to identify clusters of women based on accelerometer-measured baseline raw metabolic equivalent of task (MET) values and a normalized version of the METs ≥3 data, and to compare sociodemographic and cardiometabolic risks among these identified clusters. A total of 215 women who were enrolled in the Mobile Phone Based Physical Activity Education (mPED) trial and wore an accelerometer for at least 8 hours per day for the 7 days prior to the randomization visit were analyzed. The k-means clustering method and the Lloyd algorithm were used on the data. We used the elbow method to choose the number of clusters, looking at the percentage of variance explained as a function of the number of clusters. The results of the k-means cluster analyses of raw METs revealed three different clusters. The unengaged group (n=102) had the highest depressive symptoms score compared with the afternoon engaged (n=65) and morning engaged (n=48) groups (overall Pcluster groups using a large national dataset. ClinicalTrials.gov NCT01280812; https://clinicaltrials.gov/ct2/show/NCT01280812 (Archived by WebCite at http://www.webcitation.org/6vVyLzwft). ©Yoshimi Fukuoka, Mo Zhou, Eric Vittinghoff, William Haskell, Ken Goldberg, Anil Aswani. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 01.02.2018.

Cluster analysis of activity-time series in motor learning

DEFF Research Database (Denmark)

Balslev, Daniela; Nielsen, Finn Årup; Frutiger, Sally A.

2002-01-01

Neuroimaging studies of learning focus on brain areas where the activity changes as a function of time. To circumvent the difficult problem of model selection, we used a data-driven analytic tool, cluster analysis, which extracts representative temporal and spatial patterns from the voxel...... practice-related activity in a fronto-parieto-cerebellar network, in agreement with previous studies of motor learning. These voxels were separated from a group of voxels showing an unspecific time-effect and another group of voxels, whose activation was an artifact from smoothing. Hum. Brain Mapping 15...

Modeling, Stability Analysis and Active Stabilization of Multiple DC-Microgrids Clusters

DEFF Research Database (Denmark)

Shafiee, Qobad; Dragicevic, Tomislav; Vasquez, Juan Carlos

2014-01-01

), and more especially during interconnection with other MGs, creating dc MG clusters. This paper develops a small signal model for dc MGs from the control point of view, in order to study stability analysis and investigate effects of CPLs and line impedances between the MGs on stability of these systems....... This model can be also used to synthesis and study dynamics of control loops in dc MGs and also dc MG clusters. An active stabilization method is proposed to be implemented as a dc active power filter (APF) inside the MGs in order to not only increase damping of dc MGs at the presence of CPLs but also...... to improve their stability while connecting to the other MGs. Simulation results are provided to evaluate the developed models and demonstrate the effectiveness of proposed active stabilization technique....

User Activity Recognition in Smart Homes Using Pattern Clustering Applied to Temporal ANN Algorithm.

Science.gov (United States)

Bourobou, Serge Thomas Mickala; Yoo, Younghwan

2015-05-21

This paper discusses the possibility of recognizing and predicting user activities in the IoT (Internet of Things) based smart environment. The activity recognition is usually done through two steps: activity pattern clustering and activity type decision. Although many related works have been suggested, they had some limited performance because they focused only on one part between the two steps. This paper tries to find the best combination of a pattern clustering method and an activity decision algorithm among various existing works. For the first step, in order to classify so varied and complex user activities, we use a relevant and efficient unsupervised learning method called the K-pattern clustering algorithm. In the second step, the training of smart environment for recognizing and predicting user activities inside his/her personal space is done by utilizing the artificial neural network based on the Allen's temporal relations. The experimental results show that our combined method provides the higher recognition accuracy for various activities, as compared with other data mining classification algorithms. Furthermore, it is more appropriate for a dynamic environment like an IoT based smart home.

User Activity Recognition in Smart Homes Using Pattern Clustering Applied to Temporal ANN Algorithm

Directory of Open Access Journals (Sweden)

Serge Thomas Mickala Bourobou

2015-05-01

Full Text Available This paper discusses the possibility of recognizing and predicting user activities in the IoT (Internet of Things based smart environment. The activity recognition is usually done through two steps: activity pattern clustering and activity type decision. Although many related works have been suggested, they had some limited performance because they focused only on one part between the two steps. This paper tries to find the best combination of a pattern clustering method and an activity decision algorithm among various existing works. For the first step, in order to classify so varied and complex user activities, we use a relevant and efficient unsupervised learning method called the K-pattern clustering algorithm. In the second step, the training of smart environment for recognizing and predicting user activities inside his/her personal space is done by utilizing the artificial neural network based on the Allen’s temporal relations. The experimental results show that our combined method provides the higher recognition accuracy for various activities, as compared with other data mining classification algorithms. Furthermore, it is more appropriate for a dynamic environment like an IoT based smart home.

Bi-Level Decentralized Active Power Control for Large-Scale Wind Farm Cluster

DEFF Research Database (Denmark)

Huang, Shengli; Wu, Qiuwei; Guo, Yifei

2018-01-01

This paper presents a bi-level decentralized active power control (DAPC) for a large-scale wind farm cluster, consisting of several wind farms for better active power dispatch. In the upper level, a distributed active power control scheme based on the distributed consensus is designed to achieve...... fair active power sharing among multiple wind farms, which generates the power reference for each wind farm. A distributed estimator is used to estimate the total available power of all wind farms. In the lower level, a centralized control scheme based on the Model Predictive Control (MPC) is proposed...... to regulate active power outputs of all wind turbines (WTs) within a wind farm, which reduces the fatigue loads of WTs while tracking the power reference obtained from the upper level control. A wind farm cluster with 8 wind farms and totally 160 WTs, was used to test the control performance of the proposed...

Formation of an Approach to the Clustered Management of Foreign Economic Activity of Enterprises in the Conditions of Global Competition

Directory of Open Access Journals (Sweden)

Sushchenko Olena A.

2015-09-01

Full Text Available The article is aimed at formation of an approach to the clustered management of foreign economic activity of enterprises in the conditions of global competition. Expedience of use of the cluster approach in the field of management of foreign economic activity of enterprises has been substantiated. A basic framework has been developed and a cluster model for management of foreign economic activity of enterprises providing a description of such management as a complex mechanism with the specified parameters has been created. The basic elements of the cluster model of management of foreign economic activity of enterprise have been allocated. Purposes for selecting elemental clusters in the process of management of foreign economic activity of enterprise have been defined. The partial functions of management that display the functional purpose of the cluster model of management of foreign economic activity of enterprises, as well as the composition of its elements, have been allocated. A generalized hierarchical view of the cluster model of management of foreign economic activity of enterprises has been proposed. A scheme of the operational administration of functioning of the cluster model of management of foreign economic activity of enterprises, based on the core principles and basics of situational simulation, has been presented. Effectiveness of the presented management model is determined by the increasing share of enterprises in the external markets in the context of the relevant clusters, an expansion of the types of foreign economic activity of enterprises, implementation of innovations

Prevalence of Telomerase Activity in Human Cancer

Directory of Open Access Journals (Sweden)

Chi-Hau Chen

2011-05-01

Full Text Available Telomerase activity has been measured in a wide variety of cancerous and non-cancerous tissue types, and the vast majority of clinical studies have shown a direct correlation between it and the presence of cancerous cells. Telomerase plays a key role in cellular immortality and tumorigenesis. Telomerase is activated in 80–90% of human carcinomas, but not in normal somatic cells, therefore, its detection holds promise as a diagnostic marker for cancer. Measurable levels of telomerase have been detected in malignant cells from various samples: tissue from gestational trophoblastic neoplasms; squamous carcinoma cells from oral rinses; lung carcinoma cells from bronchial washings; colorectal carcinoma cells from colonic luminal washings; bladder carcinoma cells from urine or bladder washings; and breast carcinoma or thyroid cancer cells from fine needle aspirations. Such clinical tests for telomerase can be useful as non-invasive and cost-effective methods for early detection and monitoring of cancer. In addition, telomerase activity has been shown to correlate with poor clinical outcome in late-stage diseases such as non-small cell lung cancer, colorectal cancer, and soft tissue sarcomas. In such cases, testing for telomerase activity can be used to identify patients with a poor prognosis and to select those who might benefit from adjuvant treatment. Our review of the latest medical advances in this field reveals that telomerase holds great promise as a biomarker for early cancer detection and monitoring, and has considerable potential as the basis for developing new anticancer therapies.

Superparamagnetic nickel colloidal nanocrystal clusters with antibacterial activity and bacteria binding ability

Science.gov (United States)

Peng, Bo; Zhang, Xinglin; Aarts, Dirk G. A. L.; Dullens, Roel P. A.

2018-06-01

Recent progress in synthetic nanotechnology and the ancient use of metals in food preservation and the antibacterial treatment of wounds have prompted the development of nanometallic materials for antimicrobial applications1-4. However, the materials designed so far do not simultaneously display antimicrobial activity and the capability of binding and capturing bacteria and spores. Here, we develop a one-step pyrolysis procedure to synthesize monodisperse superparamagnetic nickel colloidal nanocrystal clusters (SNCNCs), which show both antibacterial activity and the ability to bind Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria, as well as bacterial spores. The SNCNCs are formed from a rapid burst of nickel nanoparticles, which self-assemble slowly into clusters. The clusters can magnetically extract 99.99% of bacteria and spores and provide a promising approach for the removal of microbes, including hard-to-treat microorganisms. We believe that our work illustrates the exciting opportunities that nanotechnology offers for alternative antimicrobial strategies and other applications in microbiology.

Data Clustering on Breast Cancer Data Using Firefly Algorithm with Golden Ratio Method

Directory of Open Access Journals (Sweden)

DEMIR, M.

2015-05-01

Full Text Available Heuristic methods are problem solving methods. In general, they obtain near-optimal solutions, and they do not take the care of provability of this case. The heuristic methods do not guarantee to obtain the optimal results; however, they guarantee to obtain near-optimal solutions in considerable time. In this paper, an application was performed by using firefly algorithm - one of the heuristic methods. The golden ratio was applied to different steps of firefly algorithm and different parameters of firefly algorithm to develop a new algorithm - called Firefly Algorithm with Golden Ratio (FAGR. It was shown that the golden ratio made firefly algorithm be superior to the firefly algorithm without golden ratio. At this aim, the developed algorithm was applied to WBCD database (breast cancer database to cluster data obtained from breast cancer patients. The highest obtained success rate among all executions is 96% and the highest obtained average success rate in all executions is 94.5%.

EVOLUTION AND DISTRIBUTION OF MAGNETIC FIELDS FROM ACTIVE GALACTIC NUCLEI IN GALAXY CLUSTERS. II. THE EFFECTS OF CLUSTER SIZE AND DYNAMICAL STATE

International Nuclear Information System (INIS)

Xu Hao; Li Hui; Collins, David C.; Li, Shengtai; Norman, Michael L.

2011-01-01

Theory and simulations suggest that magnetic fields from radio jets and lobes powered by their central super massive black holes can be an important source of magnetic fields in the galaxy clusters. This is Paper II in a series of studies where we present self-consistent high-resolution adaptive mesh refinement cosmological magnetohydrodynamic simulations that simultaneously follow the formation of a galaxy cluster and evolution of magnetic fields ejected by an active galactic nucleus. We studied 12 different galaxy clusters with virial masses ranging from 1 x 10 14 to 2 x 10 15 M sun . In this work, we examine the effects of the mass and merger history on the final magnetic properties. We find that the evolution of magnetic fields is qualitatively similar to those of previous studies. In most clusters, the injected magnetic fields can be transported throughout the cluster and be further amplified by the intracluster medium (ICM) turbulence during the cluster formation process with hierarchical mergers, while the amplification history and the magnetic field distribution depend on the cluster formation and magnetism history. This can be very different for different clusters. The total magnetic energies in these clusters are between 4 x 10 57 and 10 61 erg, which is mainly decided by the cluster mass, scaling approximately with the square of the total mass. Dynamically older relaxed clusters usually have more magnetic fields in their ICM. The dynamically very young clusters may be magnetized weakly since there is not enough time for magnetic fields to be amplified.

Symptom clusters and quality of life in China patients with lung ...

African Journals Online (AJOL)

Identifying symptom clusters helped clarify possible inter-relationships which may lead to the establishment of more effective symptom management interventions for patients with lung cancer in order to improve the quality of life. Keywords: symptom clusters, lung cancer, factor analysis, symptom management, quality of life

Activation and clustering of a Plasmodium falciparum var gene are affected by subtelomeric sequences.

Science.gov (United States)

Duffy, Michael F; Tang, Jingyi; Sumardy, Fransisca; Nguyen, Hanh H T; Selvarajah, Shamista A; Josling, Gabrielle A; Day, Karen P; Petter, Michaela; Brown, Graham V

2017-01-01

The Plasmodium falciparum var multigene family encodes the cytoadhesive, variant antigen PfEMP1. P. falciparum antigenic variation and cytoadhesion specificity are controlled by epigenetic switching between the single, or few, simultaneously expressed var genes. Most var genes are maintained in perinuclear clusters of heterochromatic telomeres. The active var gene(s) occupy a single, perinuclear var expression site. It is unresolved whether the var expression site forms in situ at a telomeric cluster or whether it is an extant compartment to which single chromosomes travel, thus controlling var switching. Here we show that transcription of a var gene did not require decreased colocalisation with clusters of telomeres, supporting var expression site formation in situ. However following recombination within adjacent subtelomeric sequences, the same var gene was persistently activated and did colocalise less with telomeric clusters. Thus, participation in stable, heterochromatic, telomere clusters and var switching are independent but are both affected by subtelomeric sequences. The var expression site colocalised with the euchromatic mark H3K27ac to a greater extent than it did with heterochromatic H3K9me3. H3K27ac was enriched within the active var gene promoter even when the var gene was transiently repressed in mature parasites and thus H3K27ac may contribute to var gene epigenetic memory. © 2016 Federation of European Biochemical Societies.

The Use of Cluster Analysis for Non-Continuous Variables in the Assessment of Dietary Behaviours and Physical Activities in Primary School Children

Directory of Open Access Journals (Sweden)

Zalewska Magdalena

2015-12-01

Full Text Available Physical activity, along with proper nutrition, is a very important element in child development. Lack of everyday, regular physical activity among young people is a public health problem. The aim of the study was to use cluster analysis to assess the relationship between nutrition and physical activity levels of primary school children. The study included 682 students from randomly selected elementary schools and was performed using a proprietary questionnaire during the 2013/2014 school year. The questionnaire contained questions about eating habits and physical activity, as well as the socio-economic conditions of families. Clusters of students of similar dietary habits were identified using cluster analysis and subsequently compared in terms of physical activity level. We identified four clusters, characterized by relative internal homogeneity and at the same time variability between one another in terms of number of meals throughout the day and time of their consumption. The most important characteristic of Cluster 1 was eating four meals a day including breakfast, which is the most important meal of the day. The diets of children in Cluster 2 abounded with raw vegetables and fruits. Students in Cluster 3 were characterized by a regular and varied diet. The least appropriate behaviour in the field of nutrition was observed among students belonging to Cluster 4. Cluster analysis in the studied population allowed relationships between dietary habits and physical activity to be described. By using the UIAF indicator (Moderate to Intense Physical Activity, a statistically significant association between the eating habits of the children and their physical activity levels was observed. A sufficient level of physical activity was observed in most students belonging to Cluster 3, and high levels of physical activity were observed in a small percentage of children belonging Cluster 4. An average level of physical activity was observed in a high

Activation and Molecular Targets of Peroxisome Proliferator-Activated Receptor-γ Ligands in Lung Cancer

Directory of Open Access Journals (Sweden)

Raphael A. Nemenoff

2008-01-01

Full Text Available Lung cancer is the leading cause of cancer death, and five-year survival remains poor, raising the urgency for new treatment strategies. Activation of PPARγ represents a potential target for both the treatment and prevention of lung cancer. Numerous studies have examined the effect of thiazolidinediones such as rosiglitazone and pioglitazone on lung cancer cells in vitro and in xenograft models. These studies indicate that activation of PPARγ inhibits cancer cell proliferation as well as invasiveness and metastasis. While activation of PPARγ can occur by direct binding of pharmacological ligands to the molecule, emerging data indicate that PPARγ activation can occur through engagement of other signal transduction pathways, including Wnt signaling and prostaglandin production. Data, both from preclinical models and retrospective clinical studies, indicate that activation of PPARγ may represent an attractive chemopreventive strategy. This article reviews the existing biological and mechanistic experiments focusing on the role of PPARγ in lung cancer, focusing specifically on nonsmall cell lung cancer.

Spontaneous cluster activity in the inferior olivary nucleus in brainstem slices from postnatal mice

DEFF Research Database (Denmark)

Rekling, Jens C; Reveles Jensen, Kristian; Jahnsen, Henrik

2012-01-01

-active with separate clusters at different times. The coherence between calcium transients in IO neurons decreased with Euclidean distance between the cells reaching low values at 100-200 µm distances. Intracellular recordings from IO neurons during cluster formation revealed the presence of spikelet-like potentials...

A Human Activity Recognition System Based on Dynamic Clustering of Skeleton Data

Directory of Open Access Journals (Sweden)

Alessandro Manzi

2017-05-01

Full Text Available Human activity recognition is an important area in computer vision, with its wide range of applications including ambient assisted living. In this paper, an activity recognition system based on skeleton data extracted from a depth camera is presented. The system makes use of machine learning techniques to classify the actions that are described with a set of a few basic postures. The training phase creates several models related to the number of clustered postures by means of a multiclass Support Vector Machine (SVM, trained with Sequential Minimal Optimization (SMO. The classification phase adopts the X-means algorithm to find the optimal number of clusters dynamically. The contribution of the paper is twofold. The first aim is to perform activity recognition employing features based on a small number of informative postures, extracted independently from each activity instance; secondly, it aims to assess the minimum number of frames needed for an adequate classification. The system is evaluated on two publicly available datasets, the Cornell Activity Dataset (CAD-60 and the Telecommunication Systems Team (TST Fall detection dataset. The number of clusters needed to model each instance ranges from two to four elements. The proposed approach reaches excellent performances using only about 4 s of input data (~100 frames and outperforms the state of the art when it uses approximately 500 frames on the CAD-60 dataset. The results are promising for the test in real context.

A Human Activity Recognition System Based on Dynamic Clustering of Skeleton Data.

Science.gov (United States)

Manzi, Alessandro; Dario, Paolo; Cavallo, Filippo

2017-05-11

Human activity recognition is an important area in computer vision, with its wide range of applications including ambient assisted living. In this paper, an activity recognition system based on skeleton data extracted from a depth camera is presented. The system makes use of machine learning techniques to classify the actions that are described with a set of a few basic postures. The training phase creates several models related to the number of clustered postures by means of a multiclass Support Vector Machine (SVM), trained with Sequential Minimal Optimization (SMO). The classification phase adopts the X-means algorithm to find the optimal number of clusters dynamically. The contribution of the paper is twofold. The first aim is to perform activity recognition employing features based on a small number of informative postures, extracted independently from each activity instance; secondly, it aims to assess the minimum number of frames needed for an adequate classification. The system is evaluated on two publicly available datasets, the Cornell Activity Dataset (CAD-60) and the Telecommunication Systems Team (TST) Fall detection dataset. The number of clusters needed to model each instance ranges from two to four elements. The proposed approach reaches excellent performances using only about 4 s of input data (~100 frames) and outperforms the state of the art when it uses approximately 500 frames on the CAD-60 dataset. The results are promising for the test in real context.

Differences in telomerase activity between colon and rectal cancer.

Science.gov (United States)

Ayiomamitis, Georgios D; Notas, George; Zaravinos, Apostolos; Zizi-Sermpetzoglou, Adamantia; Georgiadou, Maria; Sfakianaki, Ourania; Kouroumallis, Elias

2014-06-01

Colorectal cancer is one of the most common cancers and the third leading cause of cancer death in both sexes. The disease progresses as a multistep process and is associated with genetic alterations. One of the characteristic features of cancer is telomerase activation. We sought to evaluate the differences in telomerase activity between colon cancer and adjacent normal tissue and to correlate the differences in telomerase activity between different locations with clinicopathological factors and survival. Matched colon tumour samples and adjacent normal mucosa samples 10 cm away from the tumour were collected during colectomy. We assessed telomerase activity using real time polymerase chain reaction. Several pathological characteristics of tumours, including p53, Ki-67, p21, bcl2 and MLH1 expression were also studied. We collected samples from 49 patients. There was a significantly higher telomerase activity in colon cancer tissue than normal tissue. Adenocarcinomas of the right colon express significantly higher telomerase than left-side cancers. Colon cancers and their adjacent normal tissue had significantly more telomerase and were more positive to MLH1 than rectal cancers. The expression of p53 negatively correlated to telomerase activity and was linked to better patient survival. Colon and rectal cancers seem to have different telomerase and MLH1 profiles, and this could be another factor for their different biologic and clinical behaviour and progression. These results support the idea that the large bowel cannot be considered a uniform organ, at least in the biology of cancer.

A cluster analysis of patterns of objectively measured physical activity in Hong Kong.

Science.gov (United States)

Lee, Paul H; Yu, Ying-Ying; McDowell, Ian; Leung, Gabriel M; Lam, T H

2013-08-01

The health benefits of exercise are clear. In targeting interventions it would be valuable to know whether characteristic patterns of physical activity (PA) are associated with particular population subgroups. The present study used cluster analysis to identify characteristic hourly PA patterns measured by accelerometer. Cross-sectional design. Objectively measured PA in Hong Kong adults. Four-day accelerometer data were collected during 2009 to 2011 for 1714 participants in Hong Kong (mean age 44?2 years, 45?9% male). Two clusters were identified, one more active than the other. The ‘active cluster’ (n 480) was characterized by a routine PA pattern on weekdays and a more active and varied pattern on weekends; the other, the ‘less active cluster’ (n 1234), by a consistently low PA pattern on both weekdays and weekends with little variation from day to day. Demographic, lifestyle, PA level and health characteristics of the two clusters were compared. They differed in age, sex, smoking, income and level of PA required at work. The odds of having any chronic health conditions was lower for the active group (adjusted OR50?62, 95% CI 0?46, 0?84) but the two groups did not differ in terms of specific chronic health conditions or obesity. Implications are drawn for targeting exercise promotion programmes at the population level.

A new experimental setup for high-pressure catalytic activity measurements on surface deposited mass-selected Pt clusters

International Nuclear Information System (INIS)

Watanabe, Yoshihide; Isomura, Noritake

2009-01-01

A new experimental setup to study catalytic and electronic properties of size-selected clusters on metal oxide substrates from the viewpoint of cluster-support interaction and to formulate a method for the development of heterogeneous catalysts such as automotive exhaust catalysts has been developed. The apparatus consists of a size-selected cluster source, a photoemission spectrometer, a scanning tunneling microscope (STM), and a high-pressure reaction cell. The high-pressure reaction cell measurements provided information on catalytic properties in conditions close to practical use. The authors investigated size-selected platinum clusters deposited on a TiO 2 (110) surface using a reaction cell and STM. Catalytic activity measurements showed that the catalytic activities have a cluster-size dependency.

Zinc oxide nanorod clusters deposited seaweed cellulose sheet for antimicrobial activity.

Science.gov (United States)

Bhutiya, Priyank L; Mahajan, Mayur S; Abdul Rasheed, M; Pandey, Manoj; Zaheer Hasan, S; Misra, Nirendra

2018-06-01

Seaweed cellulose was isolated from green seaweed Ulva fasciata using a common bleaching agent. Sheet containing porous mesh was prepared from the extracted seaweed crystalline cellulose along with zinc oxide (ZnO) nanorod clusters grown over the sheet by single step hydrothermal method. Seaweed cellulose and zinc oxide nanorod clusters deposited seaweed cellulose sheet was characterized by FT-IR, XRD, TGA, and SEM-EDX. Morphology showed that the diameter of zinc oxide nanorods were around 70nm. Zinc oxide nanorod clusters deposited on seaweed cellulose sheet gave remarkable antibacterial activity towards gram-positive (Staphylococcus aureus, Bacillus ceresus, Streptococcus thermophilis) and gram-negative (Escherichia coli, Pseudomonas aeruginous) microbes. Such deposited sheet has potential applications in pharmaceutical, biomedical, food packaging, water treatment and biotechnological industries. Copyright © 2018 Elsevier B.V. All rights reserved.

Results of a lay health education intervention to increase colorectal cancer screening among Filipino Americans: A cluster randomized controlled trial.

Science.gov (United States)

Cuaresma, Charlene F; Sy, Angela U; Nguyen, Tung T; Ho, Reginald C S; Gildengorin, Ginny L; Tsoh, Janice Y; Jo, Angela M; Tong, Elisa K; Kagawa-Singer, Marjorie; Stewart, Susan L

2018-04-01

Filipino colorectal cancer (CRC) screening rates fall below Healthy People 2020 goals. In this study, the authors explore whether a lay health educator (LHE) approach can increase CRC screening among Filipino Americans ages 50 to 75 years in Hawai'i. A cluster randomized controlled trial from 2012 through 2015 compared an intervention, which consisted of LHEs delivering 2 education sessions and 2 telephone follow-up calls on CRC screening plus a CRC brochure versus an attention control, in which 2 lectures and 2 follow-up calls on nutrition and physical activity plus a CRC brochure were provided. The primary outcome was change in self-reported ever receipt of CRC screening at 6 months. Among 304 participants (77% women, 86% had > 10 years of residence in the United States), the proportion of participants who reported ever having received CRC screening increased significantly in the intervention group (from 80% to 89%; P = .0003), but not in the control group (from 73% to 74%; P = .60). After covariate adjustment, there was a significant intervention effect (odds ratio, 1.9; 95% confidence interval, 1.0-3.5). There was no intervention effect on up-to-date screening. This first randomized controlled trial for CRC screening among Hawai'i's Filipinos used an LHE intervention with mixed, but promising, results. Cancer 2018;124:1535-42. © 2018 American Cancer Society. © 2018 American Cancer Society.

Collagen attachment to the substrate controls cell clustering through migration

International Nuclear Information System (INIS)

Hou, Yue; Rodriguez, Laura Lara; Wang, Juan; Schneider, Ian C

2014-01-01

Cell clustering and scattering play important roles in cancer progression and tissue engineering. While the extracellular matrix (ECM) is known to control cell clustering, much of the quantitative work has focused on the analysis of clustering between cells with strong cell–cell junctions. Much less is known about how the ECM regulates cells with weak cell–cell contact. Clustering characteristics were quantified in rat adenocarcinoma cells, which form clusters on physically adsorbed collagen substrates, but not on covalently attached collagen substrates. Covalently attaching collagen inhibited desorption of collagen from the surface. While changes in proliferation rate could not explain differences seen in the clustering, changes in cell motility could. Cells plated under conditions that resulted in more clustering had a lower persistence time and slower migration rate than those under conditions that resulted in less clustering. Understanding how the ECM regulates clustering will not only impact the fundamental understanding of cancer progression, but also will guide the design of tissue engineered constructs that allow for the clustering or dissemination of cells throughout the construct. (paper)

Efficacy of bowel cancer appeals for promoting physical activity.

Science.gov (United States)

Jalleh, Geoffrey; Donovan, Robert J; Slevin, Terry; Dixon, Helen

2005-08-01

To investigate the potential efficacy of bowel cancer prevention messages in increasing intentions to be more physically active. A convenience sample of 281 physically inactive persons aged 30-60 years was recruited in the Perth city centre and randomly assigned to a bowel cancer and physical activity message or a heart disease and physical activity message. After reading a booklet containing information about physical activity and its link either to bowel cancer (n = 141) or cardiovascular disease (n = 140), respondents filled in a self-completion questionnaire. The main response measures were impact on intentions to be more physically active, and perceived believability and relevance of the message. Perceived believability of the message was high in both conditions. Perceived personal relevance of the message was substantially lower in the bowel cancer than the cardiovascular disease condition. Overall, the cardiovascular disease condition achieved somewhat higher behavioural intentions than the bowel cancer condition. The finding that two in three respondents in the bowel cancer condition had increased intention to increase their level of physical activity provides support for the potential efficacy of promoting physical activity in reducing the risk of bowel cancer.

Comparing 3 dietary pattern methods--cluster analysis, factor analysis, and index analysis--With colorectal cancer risk: The NIH-AARP Diet and Health Study.

Science.gov (United States)

Reedy, Jill; Wirfält, Elisabet; Flood, Andrew; Mitrou, Panagiota N; Krebs-Smith, Susan M; Kipnis, Victor; Midthune, Douglas; Leitzmann, Michael; Hollenbeck, Albert; Schatzkin, Arthur; Subar, Amy F

2010-02-15

The authors compared dietary pattern methods-cluster analysis, factor analysis, and index analysis-with colorectal cancer risk in the National Institutes of Health (NIH)-AARP Diet and Health Study (n = 492,306). Data from a 124-item food frequency questionnaire (1995-1996) were used to identify 4 clusters for men (3 clusters for women), 3 factors, and 4 indexes. Comparisons were made with adjusted relative risks and 95% confidence intervals, distributions of individuals in clusters by quintile of factor and index scores, and health behavior characteristics. During 5 years of follow-up through 2000, 3,110 colorectal cancer cases were ascertained. In men, the vegetables and fruits cluster, the fruits and vegetables factor, the fat-reduced/diet foods factor, and all indexes were associated with reduced risk; the meat and potatoes factor was associated with increased risk. In women, reduced risk was found with the Healthy Eating Index-2005 and increased risk with the meat and potatoes factor. For men, beneficial health characteristics were seen with all fruit/vegetable patterns, diet foods patterns, and indexes, while poorer health characteristics were found with meat patterns. For women, findings were similar except that poorer health characteristics were seen with diet foods patterns. Similarities were found across methods, suggesting basic qualities of healthy diets. Nonetheless, findings vary because each method answers a different question.

Clustering multilayer omics data using MuNCut.

Science.gov (United States)

Teran Hidalgo, Sebastian J; Ma, Shuangge

2018-03-14

Omics profiling is now a routine component of biomedical studies. In the analysis of omics data, clustering is an essential step and serves multiple purposes including for example revealing the unknown functionalities of omics units, assisting dimension reduction in outcome model building, and others. In the most recent omics studies, a prominent trend is to conduct multilayer profiling, which collects multiple types of genetic, genomic, epigenetic and other measurements on the same subjects. In the literature, clustering methods tailored to multilayer omics data are still limited. Directly applying the existing clustering methods to multilayer omics data and clustering each layer first and then combing across layers are both "suboptimal" in that they do not accommodate the interconnections within layers and across layers in an informative way. In this study, we develop the MuNCut (Multilayer NCut) clustering approach. It is tailored to multilayer omics data and sufficiently accounts for both across- and within-layer connections. It is based on the novel NCut technique and also takes advantages of regularized sparse estimation. It has an intuitive formulation and is computationally very feasible. To facilitate implementation, we develop the function muncut in the R package NcutYX. Under a wide spectrum of simulation settings, it outperforms competitors. The analysis of TCGA (The Cancer Genome Atlas) data on breast cancer and cervical cancer shows that MuNCut generates biologically meaningful results which differ from those using the alternatives. We propose a more effective clustering analysis of multiple omics data. It provides a new venue for jointly analyzing genetic, genomic, epigenetic and other measurements.

Rectal Cancer Survivors' Participation in Productive Activities.

Science.gov (United States)

Hornbrook, Mark C; Grant, Marcia; Wendel, Christopher; Bulkley, Joanna E; Mcmullen, Carmit K; Altschuler, Andrea; Temple, Larissa Kf; Herrinton, Lisa J; Krouse, Robert S

2017-01-01

Rectal cancer and its treatment impair survivors' productivity. To assess determinants of market and nonmarket employment, job search, volunteering, and homemaking among survivors five years or longer after diagnosis. We mailed questionnaires to 1063 survivors who were members of Kaiser Permanente (Northern California, Northwest) during 2010 and 2011. Productive activities, functional health status, and bowel management at the time of the survey. Response rate was 60.5% (577/953). Higher comorbidity burdens were associated with lower productivity for men and women rectal cancer survivors. Productive survivors were younger and had lower disease stage and age at diagnosis, higher household income and educational attainment, and fewer comorbidity burdens and workplace adjustments than did nonproductive survivors (p < 0.05 each; 2-sided). Productive rectal cancer survivors were evenly split by sex. Staying productive is associated with better mental health for rectal cancer survivors. Rectal cancer survivors with multiple chronic conditions, higher disease stage, lower productive activities, and older age need better access to medical care and closer monitoring of the quality of their care, including self-care. To capture the full extent of the involvement of survivors in all types of productive activities, research should routinely include measures of employment, searching for employment, homemaking, and volunteering. Counting market and nonmarket productive activities is innovative and recognizes the continuum of contributions survivors make to families and society. Health care systems should routinely monitor rectal cancer survivors' medical care access, comorbidities, health-related quality of life, and productive activities.

Modeling cancer registration processes with an enhanced activity diagram.

Science.gov (United States)

Lyalin, D; Williams, W

2005-01-01

Adequate instruments are needed to reflect the complexity of routine cancer registry operations properly in a business model. The activity diagram is a key instrument of the Unified Modeling Language (UML) for the modeling of business processes. The authors aim to improve descriptions of processes in cancer registration, as well as in other public health domains, through the enhancements of an activity diagram notation within the standard semantics of UML. The authors introduced the practical approach to enhance a conventional UML activity diagram, complementing it with the following business process concepts: timeline, duration for individual activities, responsibilities for individual activities within swimlanes, and descriptive text. The authors used an enhanced activity diagram for modeling surveillance processes in the cancer registration domain. Specific example illustrates the use of an enhanced activity diagram to visualize a process of linking cancer registry records with external mortality files. Enhanced activity diagram allows for the addition of more business concepts to a single diagram and can improve descriptions of processes in cancer registration, as well as in other domains. Additional features of an enhanced activity diagram allow to advance the visualization of cancer registration processes. That, in turn, promotes the clarification of issues related to the process timeline, responsibilities for particular operations, and collaborations among process participants. Our first experiences in a cancer registry best practices development workshop setting support the usefulness of such an approach.

Multi-cellular natural killer (NK) cell clusters enhance NK cell activation through localizing IL-2 within the cluster

Science.gov (United States)

Kim, Miju; Kim, Tae-Jin; Kim, Hye Mi; Doh, Junsang; Lee, Kyung-Mi

2017-01-01

Multi-cellular cluster formation of natural killer (NK) cells occurs during in vivo priming and potentiates their activation to IL-2. However, the precise mechanism underlying this synergy within NK cell clusters remains unclear. We employed lymphocyte-laden microwell technologies to modulate contact-mediated multi-cellular interactions among activating NK cells and to quantitatively assess the molecular events occurring in multi-cellular clusters of NK cells. NK cells in social microwells, which allow cell-to-cell contact, exhibited significantly higher levels of IL-2 receptor (IL-2R) signaling compared with those in lonesome microwells, which prevent intercellular contact. Further, CD25, an IL-2R α chain, and lytic granules of NK cells in social microwells were polarized toward MTOC. Live cell imaging of lytic granules revealed their dynamic and prolonged polarization toward neighboring NK cells without degranulation. These results suggest that IL-2 bound on CD25 of one NK cells triggered IL-2 signaling of neighboring NK cells. These results were further corroborated by findings that CD25-KO NK cells exhibited lower proliferation than WT NK cells, and when mixed with WT NK cells, underwent significantly higher level of proliferation. These data highlights the existence of IL-2 trans-presentation between NK cells in the local microenvironment where the availability of IL-2 is limited.

Activation-Dependent Rapid Postsynaptic Clustering of Glycine Receptors in Mature Spinal Cord Neurons

Science.gov (United States)

Eto, Kei; Murakoshi, Hideji; Watanabe, Miho; Hirata, Hiromi; Moorhouse, Andrew J.; Ishibashi, Hitoshi

2017-01-01

Abstract Inhibitory synapses are established during development but continue to be generated and modulated in strength in the mature nervous system. In the spinal cord and brainstem, presynaptically released inhibitory neurotransmitter dominantly switches from GABA to glycine during normal development in vivo. While presynaptic mechanisms of the shift of inhibitory neurotransmission are well investigated, the contribution of postsynaptic neurotransmitter receptors to this shift is not fully elucidated. Synaptic clustering of glycine receptors (GlyRs) is regulated by activation-dependent depolarization in early development. However, GlyR activation induces hyperpolarization after the first postnatal week, and little is known whether and how presynaptically released glycine regulates postsynaptic receptors in a depolarization-independent manner in mature developmental stage. Here we developed spinal cord neuronal culture of rodents using chronic strychnine application to investigate whether initial activation of GlyRs in mature stage could change postsynaptic localization of GlyRs. Immunocytochemical analyses demonstrate that chronic blockade of GlyR activation until mature developmental stage resulted in smaller clusters of postsynaptic GlyRs that could be enlarged upon receptor activation for 1 h in the mature stage. Furthermore, live cell-imaging techniques show that GlyR activation decreases its lateral diffusion at synapses, and this phenomenon is dependent on PKC, but neither Ca2+ nor CaMKII activity. These results suggest that the GlyR activation can regulate receptor diffusion and cluster size at inhibitory synapses in mature stage, providing not only new insights into the postsynaptic mechanism of shifting inhibitory neurotransmission but also the inhibitory synaptic plasticity in mature nervous system. PMID:28197549

Homogeneous pancreatic cancer spheroids mimic growth pattern of circulating tumor cell clusters and macrometastases: displaying heterogeneity and crater-like structure on inner layer.

Science.gov (United States)

Feng, Hao; Ou, Bao-Chi; Zhao, Jing-Kun; Yin, Shuai; Lu, Ai-Guo; Oechsle, Eva; Thasler, Wolfgang E

2017-09-01

Pancreatic cancer 3D in vitro models including multicellular tumor spheroid (MCTS), single cell-derived tumor spheroid (SCTS), tissue-derived tumor spheroid, and organotypic models provided powerful platforms to mimic in vivo tumor. Recent work supports that circulating tumor cell (CTC) clusters are more efficient in metastasis seeding than single CTCs. The purpose of this study is to establish 3D culture models which can mimic single CTC, monoclonal CTC clusters, and the expansion of macrometastases. Seven pancreatic ductal adenocarcinoma cell lines were used to establish MCTS and SCTS using hanging drop and ultra-low attachment plates. Spheroid immunofluorescence staining, spheroid formation assay, immunoblotting, and literature review were performed to investigate molecular biomarkers and the morphological characteristics of pancreatic tumor spheroids. Single cells experienced different growth patterns to form SCTS, like signet ring-like cells, blastula-like structures, and solid core spheroids. However, golf ball-like hollow spheroids could also be detected, especially when DanG and Capan-1 cells were cultivated with fibroblast-conditioned medium (p cell lines could also establish tumor spheroid with hanging drop plates by adding methylated cellulose. Tumor spheroids derived from pancreatic cancer cell line DanG possessed asymmetrically distributed proliferation center, immune-checkpoint properties. ß-catenin, Ki-67, and F-actin were active surrounding the crater-like structure distributing on the inner layer of viable rim cover of the spheroids, which was relevant to well-differentiated tumor cells. It is possible to establish 3D CTC cluster models from homogenous PDA cell lines using hanging drop and ultra-low attachment plates. PDA cell line displays its own intrinsic properties or heterogeneity. The mechanism of formation of the crater-like structure as well as golf ball-like structure needs further exploration.

Is the cluster environment quenching the Seyfert activity in elliptical and spiral galaxies?

Science.gov (United States)

de Souza, R. S.; Dantas, M. L. L.; Krone-Martins, A.; Cameron, E.; Coelho, P.; Hattab, M. W.; de Val-Borro, M.; Hilbe, J. M.; Elliott, J.; Hagen, A.; COIN Collaboration

2016-09-01

We developed a hierarchical Bayesian model (HBM) to investigate how the presence of Seyfert activity relates to their environment, herein represented by the galaxy cluster mass, M200, and the normalized cluster centric distance, r/r200. We achieved this by constructing an unbiased sample of galaxies from the Sloan Digital Sky Survey, with morphological classifications provided by the Galaxy Zoo Project. A propensity score matching approach is introduced to control the effects of confounding variables: stellar mass, galaxy colour, and star formation rate. The connection between Seyfert-activity and environmental properties in the de-biased sample is modelled within an HBM framework using the so-called logistic regression technique, suitable for the analysis of binary data (e.g. whether or not a galaxy hosts an AGN). Unlike standard ordinary least square fitting methods, our methodology naturally allows modelling the probability of Seyfert-AGN activity in galaxies on their natural scale, I.e. as a binary variable. Furthermore, we demonstrate how an HBM can incorporate information of each particular galaxy morphological type in an unified framework. In elliptical galaxies our analysis indicates a strong correlation of Seyfert-AGN activity with r/r200, and a weaker correlation with the mass of the host cluster. In spiral galaxies these trends do not appear, suggesting that the link between Seyfert activity and the properties of spiral galaxies are independent of the environment.

Statistical Significance for Hierarchical Clustering

Science.gov (United States)

Kimes, Patrick K.; Liu, Yufeng; Hayes, D. Neil; Marron, J. S.

2017-01-01

Summary Cluster analysis has proved to be an invaluable tool for the exploratory and unsupervised analysis of high dimensional datasets. Among methods for clustering, hierarchical approaches have enjoyed substantial popularity in genomics and other fields for their ability to simultaneously uncover multiple layers of clustering structure. A critical and challenging question in cluster analysis is whether the identified clusters represent important underlying structure or are artifacts of natural sampling variation. Few approaches have been proposed for addressing this problem in the context of hierarchical clustering, for which the problem is further complicated by the natural tree structure of the partition, and the multiplicity of tests required to parse the layers of nested clusters. In this paper, we propose a Monte Carlo based approach for testing statistical significance in hierarchical clustering which addresses these issues. The approach is implemented as a sequential testing procedure guaranteeing control of the family-wise error rate. Theoretical justification is provided for our approach, and its power to detect true clustering structure is illustrated through several simulation studies and applications to two cancer gene expression datasets. PMID:28099990

The [Mo₆Cl14]2- Cluster is Biologically Secure and Has Anti-Rotavirus Activity In Vitro.

Science.gov (United States)

Rojas-Mancilla, Edgardo; Oyarce, Alexis; Verdugo, Viviana; Morales-Verdejo, Cesar; Echeverria, Cesar; Velásquez, Felipe; Chnaiderman, Jonas; Valiente-Echeverría, Fernando; Ramirez-Tagle, Rodrigo

2017-07-05

The molybdenum cluster [Mo₆Cl 14 ] 2- is a fluorescent component with potential for use in cell labelling and pharmacology. Biological safety and antiviral properties of the cluster are as yet unknown. Here, we show the effect of acute exposition of human cells and red blood cells to the molybdenum cluster and its interaction with proteins and antiviral activity in vitro. We measured cell viability of HepG2 and EA.hy926 cell lines exposed to increasing concentrations of the cluster (0.1 to 250 µM), by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Hemolysis and morphological alterations of red blood cells, obtained from healthy donors, exposed to the cluster (10 to 200 µM) at 37 °C were analyzed. Furthermore, quenching of tryptophan residues of albumin was performed. Finally, plaque formation by rotavirus SA11 in MA104 cells treated with the cluster (100 to 300 µM) were analyzed. We found that all doses of the cluster showed similar cell viability, hemolysis, and morphology values, compared to control. Quenching of tryptophan residues of albumin suggests a protein-cluster complex formation. Finally, the cluster showed antiviral activity at 300 µM. These results indicate that the cluster [Mo₆Cl 14 ] 2- could be intravenously administered in animals at therapeutic doses for further in vivo studies and might be studied as an antiviral agent.

Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression.

Science.gov (United States)

Wu, Lijun; Zhang, Xu; Zhang, Bin; Shi, Hui; Yuan, Xiao; Sun, Yaoxiang; Pan, Zhaoji; Qian, Hui; Xu, Wenrong

2016-09-01

Exosomes are nano-sized membrane vesicles secreted by both normal and cancer cells. Emerging evidence indicates that cancer cells derived exosomes contribute to cancer progression through the modulation of tumor microenvironment. However, the effects of exosomes derived from gastric cancer cells on macrophages are not well understood. In this study, we investigated the biological role of gastric cancer cells derived exosomes in the activation of macrophages. We demonstrated that gastric cancer cells derived exosomes activated macrophages to express increased levels of proinflammatory factors, which in turn promoted tumor cell proliferation and migration. In addition, gastric cancer cells derived exosomes remarkably upregulated the phosphorylation of NF-κB in macrophages. Inhibiting the activation of NF-κB reversed the upregulation of proinflammatory factors in macrophages and blocked their promoting effects on gastric cancer cells. Moreover, we found that gastric cancer cells derived exosomes could also activate macrophages from human peripheral blood monocytes through the activation of NF-κB. In conclusion, our results suggest that gastric cancer cells derived exosomes stimulate the activation of NF-κB pathway in macrophages to promote cancer progression, which provides a potential therapeutic approach for gastric cancer by interfering with the interaction between exosomes and macrophages in tumor microenvironment.

Doxorubicin-loaded magnetic nanoparticle clusters for chemo-photothermal treatment of the prostate cancer cell line PC3

Energy Technology Data Exchange (ETDEWEB)

Zhang, Weibing; Zheng, Xinmin [Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, 430071 (China); Shen, Shun [School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai, 201203 (China); Wang, Xinghuan, E-mail: xinghuanwang9@gmail.com [Department of Urology, Zhongnan Hospital, Wuhan University, Wuhan, 430071 (China)

2015-10-16

In addition to the conventional cancer treatment such as radiotherapy, chemotherapy and surgical management, nanomedicine-based approaches have attracted widespread attention in recent years. In this paper, a promising nanocarrier, magnetic nanoparticle clusters (MNCs) as porous materials which provided enough room on the surface, was developed for loading chemotherapeutic agent of doxorubicin (DOX). Moreover, MNCs are a good near-infrared (NIR) photothermal mediator. Thus, MNCs have great potential both in photothermal therapy (PTT) and drug delivery for chemo-photothermal therapy of cancer. We firstly explored the destruction of prostate cancer in vitro by the combination of PTT and chemotherapy using DOX@MNCs. Upon NIR irradiation at 808 nm, more cancer cells were killed when PC3 cells incubated with DOX@MNCs, owing to both MNCs-mediated photothermal ablation and cytotoxicity of light-triggered DOX release. Compared with PTT or chemotherapy alone, the chemo-photothermal therapy by DOX@MNCs showed a synergistically higher therapeutic efficacy. - Highlights: • MNCs have great potential both in photothermal therapy and drug delivery. • DOX@MNCs were used for chemo-photothermal therapy of prostate cancer cells. • DOX@MNCs showed a synergistically higher therapeutic efficacy.

The clustering of diet, physical activity and sedentary behavior in children and adolescents: a review

OpenAIRE

Leech, Rebecca M; McNaughton, Sarah A; Timperio, Anna

2014-01-01

Diet, physical activity (PA) and sedentary behavior are important, yet modifiable, determinants of obesity. Recent research into the clustering of these behaviors suggests that children and adolescents have multiple obesogenic risk factors. This paper reviews studies using empirical, data-driven methodologies, such as cluster analysis (CA) and latent class analysis (LCA), to identify clustering patterns of diet, PA and sedentary behavior among children or adolescents and their associations wi...

Physical activity and sedentary behavior of cancer survivors and non-cancer individuals: results from a national survey.

Science.gov (United States)

Kim, Roy B; Phillips, Allison; Herrick, Kirsten; Helou, Marieka; Rafie, Carlin; Anscher, Mitchell S; Mikkelsen, Ross B; Ning, Yi

2013-01-01

Increasing physical activity and decreasing sedentary behavior are associated with a higher quality of life and lower mortality rates for cancer survivors, a growing population group. Studies detailing the behavior of cancer survivors are limited. Therefore, we investigated physical activity and sedentary behavior of cancer survivors using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2010. Participants were those who provided physical activity and sedentary behavior data. Those who were pregnant, physical activity, compared to non-cancer participants. These patterns are similar for breast and prostate cancer survivors, with prostate cancer survivors more likely to engage in physical activity for more than one hour per day (OR = 1.98, 95% CI (1.05, 3.71)). Our findings suggest that cancer survivors tend to have more physical activity, but they are also more likely to engage in sedentary behavior.

A prospective study of occupational physical activity and breast cancer risk.

Science.gov (United States)

Ekenga, Christine C; Parks, Christine G; Sandler, Dale P

2015-12-01

Physical activity has been associated with reduced breast cancer risk, but studies of occupational activity have produced inconsistent results. The purpose of this study was to evaluate the relationship between occupational physical activity and breast cancer in a prospective study of women with a family history of breast cancer. We studied breast cancer risk in 47,649 Sister Study participants with an occupational history. Information on occupational activity and breast cancer risk factors was collected during baseline interviews (2004-2009). Physical activity at each job was self-reported and categorized as mostly sitting, sitting and standing equally, mostly standing, and active. Multivariable Cox proportional hazards regression was used to evaluate associations between lifetime occupational activity and incident breast cancer, after adjusting for established risk factors and recreational activity. During follow-up, a total of 1,798 breast cancer diagnoses were reported. Compared with women who did not spend any time in active jobs, women who spent a high proportion (≥75%) of their working years in active jobs had a reduced risk of breast cancer (HR 0.72; 95% CI 0.52-0.98). Associations were strongest among overweight (HR 0.64; 95% CI 0.42-0.98) and postmenopausal (HR 0.67; 95% CI 0.45-0.98) women. Occupational activity was associated with a reduced risk of breast cancer. Occupational activity is a domain of physical activity that should be further examined in studies of postmenopausal breast cancer risk. Additional research is necessary to better understand the mechanisms underlying the relationships between occupational activity, body size, and breast cancer.

Curcumin sensitizes prostate cancer cells to radiation partly via epigenetic activation of miR-143 and miR-143 mediated autophagy inhibition.

Science.gov (United States)

Liu, Jianbo; Li, Min; Wang, Yuewei; Luo, Jianchao

2017-08-01

Curcumin has been reported as a radiosensitizer in prostate cancer. But the underlying mechanism is not well understood. In this study, we firstly assessed how curcumin affects the expression of miR-143/miR-145 cluster. Then, we investigated whether miR-143 is involved in regulation of radiosensitivity and its association with autophagy in prostate cancer cells. Our data showed that PC3, DU145 and LNCaP cells treated with curcumin had significantly restored miR-143 and miR-145 expression. Curcumin showed similar effect as 5-AZA-dC on reducing methylation of CpG dinucleotides in miR-143 promoter. In addition, curcumin treatment reduced the expression of DNMT1 and DNMT3B, which contribute to promoter hypermethylation of the miR-143/miR-145 cluster. Therefore, we infer that curcumin can restore miR-143 and miR-145 expression via hypomethylation. MiR-143 overexpression and curcumin pretreatment enhanced radiation induced cancer cell growth inhibition and apoptosis. MiR-143 and curcumin remarkably reduced radiation-induced autophagy in PC3 and DU145 cells. MiR-143 overexpression alone also reduced the basal level of autophagy in DU145 cells. Mechanistically, miR-143 can suppress autophagy in prostate cancer cells at least via downregulating ATG2B. Based on these findings, we infer that curcumin sensitizes prostate cancer cells to radiation partly via epigenetic activation of miR-143 and miR-143 mediated autophagy inhibition.

Evaluation of a Bladder Cancer Cluster in a Population of Criminal Investigators with the Bureau of Alcohol, Tobacco, Firearms and Explosives—Part 1: The Cancer Incidence

Directory of Open Access Journals (Sweden)

Susan R. Davis

2012-01-01

Full Text Available This study investigated a bladder cancer cluster in a cohort of employees, predominately criminal investigators, participating in a medical surveillance program with the United States Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF between 1995 and 2007. Standardized incidence ratios (SIRs were used to compare cancer incidences in the ATF population and the US reference population. Seven cases of bladder cancer (five cases verified by pathology report at time of analysis were identified among a total employee population of 3,768 individuals. All cases were white males and criminal investigators. Six of seven cases were in the 30 to 49 age range at the time of diagnosis. The SIRs for white male criminal investigators undergoing examinations were 7.63 (95% confidence interval = 3.70–15.75 for reported cases and 5.45 (2.33–12.76 for verified cases. White male criminal investigators in the ATF population are at statistically significant increased risk for bladder cancer.

Comparison of tests for spatial heterogeneity on data with global clustering patterns and outliers

Directory of Open Access Journals (Sweden)

Hachey Mark

2009-10-01

Full Text Available Abstract Background The ability to evaluate geographic heterogeneity of cancer incidence and mortality is important in cancer surveillance. Many statistical methods for evaluating global clustering and local cluster patterns are developed and have been examined by many simulation studies. However, the performance of these methods on two extreme cases (global clustering evaluation and local anomaly (outlier detection has not been thoroughly investigated. Methods We compare methods for global clustering evaluation including Tango's Index, Moran's I, and Oden's I*pop; and cluster detection methods such as local Moran's I and SaTScan elliptic version on simulated count data that mimic global clustering patterns and outliers for cancer cases in the continental United States. We examine the power and precision of the selected methods in the purely spatial analysis. We illustrate Tango's MEET and SaTScan elliptic version on a 1987-2004 HIV and a 1950-1969 lung cancer mortality data in the United States. Results For simulated data with outlier patterns, Tango's MEET, Moran's I and I*pop had powers less than 0.2, and SaTScan had powers around 0.97. For simulated data with global clustering patterns, Tango's MEET and I*pop (with 50% of total population as the maximum search window had powers close to 1. SaTScan had powers around 0.7-0.8 and Moran's I has powers around 0.2-0.3. In the real data example, Tango's MEET indicated the existence of global clustering patterns in both the HIV and lung cancer mortality data. SaTScan found a large cluster for HIV mortality rates, which is consistent with the finding from Tango's MEET. SaTScan also found clusters and outliers in the lung cancer mortality data. Conclusion SaTScan elliptic version is more efficient for outlier detection compared with the other methods evaluated in this article. Tango's MEET and Oden's I*pop perform best in global clustering scenarios among the selected methods. The use of SaTScan for

Effect of Breast Cancer on Physical Activity in Women

Directory of Open Access Journals (Sweden)

Kalinowski Paweł

2017-12-01

Full Text Available Introduction. Breast cancer is the most commonly found type of cancer in women. One cancer risk factor related to lifestyle that seems to be particularly worth examining is physical activity. The aims of the study were to analyse the physical activity of women who had been diagnosed with breast cancer for the first time and had undergone surgical treatment as well as to determine how their physical activity patterns changed with respect to the patterns from before the diagnosis.

Prediction of in vitro and in vivo oestrogen receptor activity using hierarchical clustering

Science.gov (United States)

In this study, hierarchical clustering classification models were developed to predict in vitro and in vivo oestrogen receptor (ER) activity. Classification models were developed for binding, agonist, and antagonist in vitro ER activity and for mouse in vivo uterotrophic ER bindi...

Active learning for semi-supervised clustering based on locally linear propagation reconstruction.

Science.gov (United States)

Chang, Chin-Chun; Lin, Po-Yi

2015-03-01

The success of semi-supervised clustering relies on the effectiveness of side information. To get effective side information, a new active learner learning pairwise constraints known as must-link and cannot-link constraints is proposed in this paper. Three novel techniques are developed for learning effective pairwise constraints. The first technique is used to identify samples less important to cluster structures. This technique makes use of a kernel version of locally linear embedding for manifold learning. Samples neither important to locally linear propagation reconstructions of other samples nor on flat patches in the learned manifold are regarded as unimportant samples. The second is a novel criterion for query selection. This criterion considers not only the importance of a sample to expanding the space coverage of the learned samples but also the expected number of queries needed to learn the sample. To facilitate semi-supervised clustering, the third technique yields inferred must-links for passing information about flat patches in the learned manifold to semi-supervised clustering algorithms. Experimental results have shown that the learned pairwise constraints can capture the underlying cluster structures and proven the feasibility of the proposed approach. Copyright © 2014 Elsevier Ltd. All rights reserved.

Physical Activity in Puerto Rican Breast Cancer Survivors.

Science.gov (United States)

Tirado-Gómez, Maribel; Hughes, Daniel C; González-Mercado, Velda; Treviño-Whitaker, Rose A; Basen-Engquist, Karen

2016-06-01

Breast cancer survivors do not engage in appropriate levels of physical activity, despite the known benefits of such activity. This study aims to describe physical-activity levels and the barriers to it in a group of Puerto Rican breast cancer survivors, as well as detailing their preferences for an intervention. Participants who finished their chemotherapy and/or radiotherapy for breast cancer at least 4 months prior to the study were included. Demographic, anthropometric, and clinical data were obtained. The Godin Leisure-Time Exercise Questionnaire (GLTEQ) and questionnaires on exercise self-efficacy, barriers to self-efficacy, modeling, and social support were filled out by study participants. Data on access to exercise equipment and preferences regarding a physical-activity intervention were collected. Descriptive statistics and correlation analyses were performed. Fifty breast cancer survivors were recruited. Almost all the participants reported that they did not engage in any kind of strenuous physical activity (94%), with more than three fourths (76%) reporting that they did not even participate in any kind of moderate physical activity. The GLTEQ score was associated with barriers to selfefficacy, while the association with exercise self-efficacy approached significance (p = 0.055). Nearly half of the patients (44%) had access to exercise equipment. Preferred methods for the delivery of physical-activity interventions were participating in group settings (72%) and receiving material in the postal mail (44%). The study described herein reports on the low levels of physical activity being practiced by a group of Puerto Rican breast cancer survivors, despite the fact that many of them had access to exercise equipment and facilities. Further studies aimed at understanding breast cancer survivors' barriers to physical activity and at developing culturally competent interventions to increase the levels of such activity are warranted.

The N-terminal domain of human DNA helicase Rtel1 contains a redox active iron-sulfur cluster.

Science.gov (United States)

Landry, Aaron P; Ding, Huangen

2014-01-01

Human telomere length regulator Rtel1 is a superfamily II DNA helicase and is essential for maintaining proper length of telomeres in chromosomes. Here we report that the N-terminal domain of human Rtel1 (RtelN) expressed in Escherichia coli cells produces a protein that contains a redox active iron-sulfur cluster with the redox midpoint potential of -248 ± 10 mV (pH 8.0). The iron-sulfur cluster in RtelN is sensitive to hydrogen peroxide and nitric oxide, indicating that reactive oxygen/nitrogen species may modulate the DNA helicase activity of Rtel1 via modification of its iron-sulfur cluster. Purified RtelN retains a weak binding affinity for the single-stranded (ss) and double-stranded (ds) DNA in vitro. However, modification of the iron-sulfur cluster by hydrogen peroxide or nitric oxide does not significantly affect the DNA binding activity of RtelN, suggesting that the iron-sulfur cluster is not directly involved in the DNA interaction in the N-terminal domain of Rtel1.

The N-Terminal Domain of Human DNA Helicase Rtel1 Contains a Redox Active Iron-Sulfur Cluster

Directory of Open Access Journals (Sweden)

Aaron P. Landry

2014-01-01

Full Text Available Human telomere length regulator Rtel1 is a superfamily II DNA helicase and is essential for maintaining proper length of telomeres in chromosomes. Here we report that the N-terminal domain of human Rtel1 (RtelN expressed in Escherichia coli cells produces a protein that contains a redox active iron-sulfur cluster with the redox midpoint potential of −248 ± 10 mV (pH 8.0. The iron-sulfur cluster in RtelN is sensitive to hydrogen peroxide and nitric oxide, indicating that reactive oxygen/nitrogen species may modulate the DNA helicase activity of Rtel1 via modification of its iron-sulfur cluster. Purified RtelN retains a weak binding affinity for the single-stranded (ss and double-stranded (ds DNA in vitro. However, modification of the iron-sulfur cluster by hydrogen peroxide or nitric oxide does not significantly affect the DNA binding activity of RtelN, suggesting that the iron-sulfur cluster is not directly involved in the DNA interaction in the N-terminal domain of Rtel1.

Redefining the Breast Cancer Exosome Proteome by Tandem Mass Tag Quantitative Proteomics and Multivariate Cluster Analysis.

Science.gov (United States)

Clark, David J; Fondrie, William E; Liao, Zhongping; Hanson, Phyllis I; Fulton, Amy; Mao, Li; Yang, Austin J

2015-10-20

Exosomes are microvesicles of endocytic origin constitutively released by multiple cell types into the extracellular environment. With evidence that exosomes can be detected in the blood of patients with various malignancies, the development of a platform that uses exosomes as a diagnostic tool has been proposed. However, it has been difficult to truly define the exosome proteome due to the challenge of discerning contaminant proteins that may be identified via mass spectrometry using various exosome enrichment strategies. To better define the exosome proteome in breast cancer, we incorporated a combination of Tandem-Mass-Tag (TMT) quantitative proteomics approach and Support Vector Machine (SVM) cluster analysis of three conditioned media derived fractions corresponding to a 10 000g cellular debris pellet, a 100 000g crude exosome pellet, and an Optiprep enriched exosome pellet. The quantitative analysis identified 2 179 proteins in all three fractions, with known exosomal cargo proteins displaying at least a 2-fold enrichment in the exosome fraction based on the TMT protein ratios. Employing SVM cluster analysis allowed for the classification 251 proteins as "true" exosomal cargo proteins. This study provides a robust and vigorous framework for the future development of using exosomes as a potential multiprotein marker phenotyping tool that could be useful in breast cancer diagnosis and monitoring disease progression.

Cancer-preventive activities of tocopherols and tocotrienols.

Science.gov (United States)

Ju, Jihyeung; Picinich, Sonia C; Yang, Zhihong; Zhao, Yang; Suh, Nanjoo; Kong, Ah-Ng; Yang, Chung S

2010-04-01

The cancer-preventive activity of vitamin E has been studied. Whereas some epidemiological studies have suggested a protective effect of vitamin E against cancer formation, many large-scale intervention studies with alpha-tocopherol (usually large doses) have not demonstrated a cancer-preventive effect. Studies on alpha-tocopherol in animal models also have not demonstrated robust cancer prevention effects. One possible explanation for the lack of demonstrable cancer-preventive effects is that high doses of alpha-tocopherol decrease the blood and tissue levels of delta-tocopherols. It has been suggested that gamma-tocopherol, due to its strong anti-inflammatory and other activities, may be the more effective form of vitamin E in cancer prevention. Our recent results have demonstrated that a gamma-tocopherol-rich mixture of tocopherols inhibits colon, prostate, mammary and lung tumorigenesis in animal models, suggesting that this mixture may have a high potential for applications in the prevention of human cancer. In this review, we discuss biochemical properties of tocopherols, results of possible cancer-preventive effects in humans and animal models and possible mechanisms involved in the inhibition of carcinogenesis. Based on this information, we propose that a gamma-tocopherol-rich mixture of tocopherols is a very promising cancer-preventive agent and warrants extensive future research.

A Grounded Theory Approach to Physical Activity and Advanced Cancer

Directory of Open Access Journals (Sweden)

Sonya S. Lowe

2015-11-01

Full Text Available Background: Physical activity has demonstrated benefits in cancer-related fatigue and physical functioning in early-stage cancer patients, however the role of physical activity at the end stage of cancer has not been established. To challenge positivist–empiricist assumptions, I am seeking to develop a new theoretical framework that is grounded in the advanced cancer patient’s experience of activity. Aim: To gain an in-depth understanding of the experience of activity and quality of life in advanced cancer patients. Objectives: (1 To explore the meaning of activity for advanced cancer patients in the context of their day-to-day life, (2 to elicit advanced cancer patients’ perceptions of activity with respect to their quality of life, and (3 to elicit advanced cancer patients’ views of barriers and facilitators to activity in the context of their day-to-day life. Study Design: A two-phase, cross-sectional, qualitative study will be conducted through the postpositivist lens of subtle realism and informed by the principles of grounded theory methods. Study Methods: Advanced cancer patients will be recruited through the outpatient department of a tertiary cancer center. For Phase one, participants will wear an activPAL™ activity monitor and fill out a daily record sheet for seven days duration. For Phase two, the activity monitor output and daily record sheets will be used as qualitative probes for face-to-face, semistructured interviews. Concurrent coding, constant comparative analysis, and theoretical sampling will continue with the aim of achieving as close as possible to theoretical saturation. Ethics and Discussion: Ethical and scientific approval will be obtained by all local institutional review boards prior to study commencement. The findings will generate new mid-level theory about the experience of activity and quality of life in advanced cancer patients and aid in the development of a new theoretical framework for designing

Clustering of Sun Exposure Measurements

OpenAIRE

Have, Anna Szynkowiak; Larsen, Jan; Hansen, Lars Kai; Philipsen, Peter Alshede; Thieden, Elisabeth; Wulf, Hans Christian

2002-01-01

In a medically motivated Sun-exposure study, questionnaires concerning Sun-habits were collected from a number of subjects together with UV radiation measurements. This paper focuses on identifying clusters in the heterogeneous set of data for the purpose of understanding possible relations between Sun-habits exposure and eventually assessing the risk of skin cancer. A general probabilistic framework originally developed for text and Web mining is demonstrated to be useful for clustering of b...

Physical activity can lower risk of 13 types of cancer

Science.gov (United States)

A new study of the relationship between physical activity and cancer has shown that greater levels of leisure-time physical activity were associated with a lower risk of developing 13 different types of cancer; the risk of developing seven cancer types was 20 percent lower among the most active participants as compared with the least active participants.

Primary lung cancer coexisting with active pulmonary tuberculosis.

Science.gov (United States)

Varol, Y; Varol, U; Unlu, M; Kayaalp, I; Ayranci, A; Dereli, M S; Guclu, S Z

2014-09-01

Lung cancer and pulmonary tuberculosis (TB) comorbidity is a clinical problem that presents a challenge for the diagnosis and treatment of both diseases. To clarify the clinical and survival characteristics of cases with both lung cancer and active pulmonary TB. From 2008 to 2013, 3350 TB patients admitted to the TB Department of the Chest Diseases Hospital of Izmir, Turkey, were evaluated. In 38 (1.1%) male patients, lung cancer and TB were found to coexist. Almost all of the patients were diagnosed at Stage III (n = 14, 36.8%) or IV (n = 17, 44.7%) lung cancer, whereas four (10.6%) had Stage II and three (7.9%) had Stage I disease. Squamous cell lung cancer was the predominant histology (n = 23, 60.7%). The median overall survival among patients was 13.4 months (95%CI 8.09-18.8). One-year survival rates for patients with Stages I, II, III and IV were respectively 100%, 75%, 57% and 40%. The present study demonstrates that lung cancer combined with active pulmonary TB most frequently presents as squamous cell carcinoma, with a male predominance. The overall survival of lung cancer patients did not change even with concomitant active TB.

Anti-cancer activities of Ganoderma lucidum: active ingredients and pathways

OpenAIRE

Chi H.J. Kao; Amalini C. Jesuthasan; Karen S. Bishop; Marcus P. Glucina; Lynnette R. Ferguson

2013-01-01

ABSTRACTGanoderma lucidum, commonly referred to as Lingzhi, has been used in Asia for health promotion for centuries. The anti-cancer effects of G. lucidum have been demonstrated in both in vitro and in vivo studies. In addition, the observed anti-cancer activities of Ganoderma have prompted its usage by cancer patients alongside chemotherapy.The main two bioactive components of G. lucidum can be broadly grouped into triterpenes and polysaccharides. Despite triterpenes and polysaccharides bei...

Adipocyte activation of cancer stem cell signaling in breast cancer

Institute of Scientific and Technical Information of China (English)

Benjamin; Wolfson; Gabriel; Eades; Qun; Zhou

2015-01-01

Signaling within the tumor microenvironment has a critical role in cancer initiation and progression. Adipocytes, one of the major components of the breast microenvironment,have been shown to provide pro-tumorigenic signals that promote cancer cell proliferation and invasiveness in vitro and tumorigenicity in vivo. Adipocyte secreted factors such as leptin and interleukin-6(IL-6) have a paracrine effect on breast cancer cells. In adipocyte-adjacent breast cancer cells, the leptin and IL-6 signaling pathways activate janus kinase 2/signal transducer and activatorof transcription 5, promoting the epithelial-mesenchymal transition, and upregulating stemness regulators such as Notch, Wnt and the Sex determining region Y-box 2/octamer binding transcription factor 4/Nanog signaling axis. In this review we will summarize the major signaling pathways that regulate cancer stem cells in breast cancer and describe the effects that adipocyte secreted IL-6 and leptin have on breast cancer stem cell signaling. Finally we will introduce a new potential treatment paradigm of inhibiting the adipocyte-breast cancer cell signaling via targeting the IL-6 or leptin pathways.

The Role of MRI in Prostate Cancer Active Surveillance

Directory of Open Access Journals (Sweden)

Linda M. Johnson

2014-01-01

Full Text Available Prostate cancer is the most common cancer diagnosis in American men, excluding skin cancer. The clinical behavior of prostate cancer varies from low-grade, slow growing tumors to high-grade aggressive tumors that may ultimately progress to metastases and cause death. Given the high incidence of men diagnosed with prostate cancer, conservative treatment strategies such as active surveillance are critical in the management of prostate cancer to reduce therapeutic complications of radiation therapy or radical prostatectomy. In this review, we will review the role of multiparametric MRI in the selection and follow-up of patients on active surveillance.

The Spots and Activity of Stars in the Beehive Cluster Observed by the Kepler Space Telescope (K2)

Science.gov (United States)

Savanov, I. S.; Kalinicheva, E. S.; Dmitrienko, E. S.

2018-05-01

The spottedness parameters S (the fraction of the visible surface of the star occupied by spots) characterizing the activity of 674 stars in the Beehive Cluster (age 650 Myr) are estimated, together with variations of this parameter as a function of the rotation period, Rossby number Ro and other characteristics of the stars. The activity of the stars in this cluster is lower than the activity of stars in the younger Pleiades (125 Myr). The average S value for the Beehive Cluster stars is 0.014, while Pleiades stars have the much higher average value 0.052. The activity parameters of 61 solar-type stars in the Beehive Cluster, similar Hyades stars (of about the same age), and stars in the younger Pleiades are compared. The average S value of such objects in the Beehive Cluster is 0.014± 0.008, nearly coincident with the estimate obtained for solar-type Hyades stars. The rotation periods of these objects are 9.1 ± 3.4 day, on average, in agreement with the average rotation period of the Hyades stars (8.6 d ). Stars with periods exceeding 3-4 d are more numerous in the Beehive Cluster than in the Pleiades, and their periods have a larger range, 3-30 d . The characteristic dependence with a kink at Ro (saturation) = 0.13 is not observed in the S-Rossby number diagram for the Beehive and Hyades stars, only a clump of objects with Rossby numbers Ro > 0.7. The spottedness data for the Beehive Cluster and Hyades stars are in good agreement with the S values for dwarfs with ages of 600-700 Myr. This provides evidence for the reliability of the results of gyrochronological calibrations. The data for the Beehive and Pleiades stars are used to analyze variations in the spot-forming activity for a large number of stars of the same age that are members of a single cluster. A joint consideration of the data for two clusters can be used to draw conclusions about the time evolution of the activity of stars of different masses (over a time interval of the order of 500 Myr).

Clustering gene expression regulators: new approach to disease subtyping.

Directory of Open Access Journals (Sweden)

Mikhail Pyatnitskiy

Full Text Available One of the main challenges in modern medicine is to stratify different patient groups in terms of underlying disease molecular mechanisms as to develop more personalized approach to therapy. Here we propose novel method for disease subtyping based on analysis of activated expression regulators on a sample-by-sample basis. Our approach relies on Sub-Network Enrichment Analysis algorithm (SNEA which identifies gene subnetworks with significant concordant changes in expression between two conditions. Subnetwork consists of central regulator and downstream genes connected by relations extracted from global literature-extracted regulation database. Regulators found in each patient separately are clustered together and assigned activity scores which are used for final patients grouping. We show that our approach performs well compared to other related methods and at the same time provides researchers with complementary level of understanding of pathway-level biology behind a disease by identification of significant expression regulators. We have observed the reasonable grouping of neuromuscular disorders (triggered by structural damage vs triggered by unknown mechanisms, that was not revealed using standard expression profile clustering. For another experiment we were able to suggest the clusters of regulators, responsible for colorectal carcinoma vs adenoma discrimination and identify frequently genetically changed regulators that could be of specific importance for the individual characteristics of cancer development. Proposed approach can be regarded as biologically meaningful feature selection, reducing tens of thousands of genes down to dozens of clusters of regulators. Obtained clusters of regulators make possible to generate valuable biological hypotheses about molecular mechanisms related to a clinical outcome for individual patient.

TLR-activated repression of Fe-S cluster biogenesis drives a metabolic shift and alters histone and tubulin acetylation.

Science.gov (United States)

Tong, Wing-Hang; Maio, Nunziata; Zhang, De-Liang; Palmieri, Erika M; Ollivierre, Hayden; Ghosh, Manik C; McVicar, Daniel W; Rouault, Tracey A

2018-05-22

Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common feature in a growing list of human Fe-S cluster biogenesis disorders, including Friedreich ataxia and GLRX5-related sideroblastic anemia. Here, our studies showed that restriction of Fe-S cluster biogenesis not only compromised mitochondrial oxidative metabolism but also resulted in decreased overall histone acetylation and increased H3K9me3 levels in the nucleus and increased acetylation of α-tubulin in the cytosol by decreasing the lipoylation of the pyruvate dehydrogenase complex, decreasing levels of succinate dehydrogenase and the histone acetyltransferase ELP3, and increasing levels of the tubulin acetyltransferase MEC17. Previous studies have shown that the metabolic shift in Toll-like receptor (TLR)-activated myeloid cells involves rapid activation of glycolysis and subsequent mitochondrial respiratory failure due to nitric oxide (NO)-mediated damage to Fe-S proteins. Our studies indicated that TLR activation also actively suppresses many components of the Fe-S cluster biogenesis machinery, which exacerbates NO-mediated damage to Fe-S proteins by interfering with cluster recovery. These results reveal new regulatory pathways and novel roles of the Fe-S cluster biogenesis machinery in modifying the epigenome and acetylome and provide new insights into the etiology of Fe-S cluster biogenesis disorders.

Machine Learning Detects Pan-cancer Ras Pathway Activation in The Cancer Genome Atlas

Directory of Open Access Journals (Sweden)

Gregory P. Way

2018-04-01

Full Text Available Summary: Precision oncology uses genomic evidence to match patients with treatment but often fails to identify all patients who may respond. The transcriptome of these “hidden responders” may reveal responsive molecular states. We describe and evaluate a machine-learning approach to classify aberrant pathway activity in tumors, which may aid in hidden responder identification. The algorithm integrates RNA-seq, copy number, and mutations from 33 different cancer types across The Cancer Genome Atlas (TCGA PanCanAtlas project to predict aberrant molecular states in tumors. Applied to the Ras pathway, the method detects Ras activation across cancer types and identifies phenocopying variants. The model, trained on human tumors, can predict response to MEK inhibitors in wild-type Ras cell lines. We also present data that suggest that multiple hits in the Ras pathway confer increased Ras activity. The transcriptome is underused in precision oncology and, combined with machine learning, can aid in the identification of hidden responders. : Way et al. develop a machine-learning approach using PanCanAtlas data to detect Ras activation in cancer. Integrating mutation, copy number, and expression data, the authors show that their method detects Ras-activating variants in tumors and sensitivity to MEK inhibitors in cell lines. Keywords: Gene expression, machine learning, Ras, NF1, KRAS, NRAS, HRAS, pan-cancer, TCGA, drug sensitivity

Functional Interference Clusters in Cancer Patients With Bone Metastases: A Secondary Analysis of RTOG 9714

International Nuclear Information System (INIS)

Chow, Edward; James, Jennifer; Barsevick, Andrea; Hartsell, William; Ratcliffe, Sarah; Scarantino, Charles; Ivker, Robert; Roach, Mack; Suh, John; Petersen, Ivy; Konski, Andre; Demas, William; Bruner, Deborah

2010-01-01

Purpose: To explore the relationships (clusters) among the functional interference items in the Brief Pain Inventory (BPI) in patients with bone metastases. Methods: Patients enrolled in the Radiation Therapy Oncology Group (RTOG) 9714 bone metastases study were eligible. Patients were assessed at baseline and 4, 8, and 12 weeks after randomization for the palliative radiotherapy with the BPI, which consists of seven functional items: general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life. Principal component analysis with varimax rotation was used to determine the clusters between the functional items at baseline and the follow-up. Cronbach's alpha was used to determine the consistency and reliability of each cluster at baseline and follow-up. Results: There were 448 male and 461 female patients, with a median age of 67 years. There were two functional interference clusters at baseline, which accounted for 71% of the total variance. The first cluster (physical interference) included normal work and walking ability, which accounted for 58% of the total variance. The second cluster (psychosocial interference) included relations with others and sleep, which accounted for 13% of the total variance. The Cronbach's alpha statistics were 0.83 and 0.80, respectively. The functional clusters changed at week 12 in responders but persisted through week 12 in nonresponders. Conclusion: Palliative radiotherapy is effective in reducing bone pain. Functional interference component clusters exist in patients treated for bone metastases. These clusters changed over time in this study, possibly attributable to treatment. Further research is needed to examine these effects.

Using hierarchical clustering methods to classify motor activities of COPD patients from wearable sensor data

Directory of Open Access Journals (Sweden)

Reilly John J

2005-06-01

Full Text Available Abstract Background Advances in miniature sensor technology have led to the development of wearable systems that allow one to monitor motor activities in the field. A variety of classifiers have been proposed in the past, but little has been done toward developing systematic approaches to assess the feasibility of discriminating the motor tasks of interest and to guide the choice of the classifier architecture. Methods A technique is introduced to address this problem according to a hierarchical framework and its use is demonstrated for the application of detecting motor activities in patients with chronic obstructive pulmonary disease (COPD undergoing pulmonary rehabilitation. Accelerometers were used to collect data for 10 different classes of activity. Features were extracted to capture essential properties of the data set and reduce the dimensionality of the problem at hand. Cluster measures were utilized to find natural groupings in the data set and then construct a hierarchy of the relationships between clusters to guide the process of merging clusters that are too similar to distinguish reliably. It provides a means to assess whether the benefits of merging for performance of a classifier outweigh the loss of resolution incurred through merging. Results Analysis of the COPD data set demonstrated that motor tasks related to ambulation can be reliably discriminated from tasks performed in a seated position with the legs in motion or stationary using two features derived from one accelerometer. Classifying motor tasks within the category of activities related to ambulation requires more advanced techniques. While in certain cases all the tasks could be accurately classified, in others merging clusters associated with different motor tasks was necessary. When merging clusters, it was found that the proposed method could lead to more than 12% improvement in classifier accuracy while retaining resolution of 4 tasks. Conclusion Hierarchical

Cluster as a Tool to Increase the Competitiveness and Innovative Activity of Enterprises of the Defense Industry Complex

Directory of Open Access Journals (Sweden)

Katrina B. Dobrova

2017-01-01

Full Text Available Purpose: the main goal of the publication is to make a comprehensive study of the possible application of the cluster approach to improve the competitiveness and innovation activity of enterprises of the defense industry complex.Methods: the methodology of the research is based on the collection and analysis of initial data and information, the article uses a systematic approach to the study of socio-economic processes and phenomena. The research is based on modern theory of competition, innovation, as well as the modern paradigm of cluster development of the economy. In preparing the study, practical materials from Corporation “Rostec”.Results: the article gives the notion of cluster, the prospects for the use of the cluster approach to enhance competitiveness and innovation enterprises of the military-industrial complex. It is noted that the activation of interaction with the “civil sector” is particularly relevant in the context of the reduction of the state defense order, and the theory and practice of cluster management offers a number of forms of cluster interaction between the enterprises of the defense industry and the civil sector. It is emphasized that the development of cluster mechanisms can solve a number of problems related to the insufficient financial stability of defense industry enterprises in the context of a reduction in the state defense order, low innovation activity and the lack of developed models of interaction with small innovative enterprises. Ultimately, the use of cluster mechanisms in the development of defense enterprises is intended to enhance the competitiveness of the complex, both nationally and globally. It is stated that the existing clusters are not able to fully solve a number of specific tasks related to the diversification of integrated defense industry structures. Attention is drawn to the fact that existing clusters are not able to fully solve a number of specific tasks related to the

A Cluster-Analytical Approach towards Physical Activity and Eating Habits among 10-Year-Old Children

Science.gov (United States)

Sabbe, Dieter; De Bourdeaudhuij, I.; Legiest, E.; Maes, L.

2008-01-01

The purpose was to investigate whether clusters--based on physical activity (PA) and eating habits--can be found among children, and to explore subgroups' characteristics. A total of 1725 10-year olds completed a self-administered questionnaire. K-means cluster analysis was based on the weekly quantity of vigorous and moderate PA, the excess index…

Parents' perceptions of skin cancer threat and children's physical activity.

Science.gov (United States)

Tran, Alexander D; Aalborg, Jenny; Asdigian, Nancy L; Morelli, Joseph G; Mokrohisky, Stefan T; Dellavalle, Robert P; Berwick, Marianne; Box, Neil F; Crane, Lori A

2012-01-01

Sun exposure is a major risk factor for skin cancer, but without physical activity, children are at risk of childhood obesity. The objective of this study was to explore relationships between parental perceptions of skin cancer threat, sun protection behaviors, physical activity, and body mass index (BMI) in children. This is a cross-sectional analysis nested within the Colorado Kids Sun Care Program sun safety intervention trial. In summer 2007, parent telephone interviews provided data on demographics, perceptions of skin cancer threat, sun protection behaviors, and physical activity. Physical examinations provided data on phenotype, freckling, and BMI. Data from 999 Colorado children born in 1998 were included in analysis. We used analysis of variance, Spearman's rho (ρ) correlation, and multivariable linear regression analysis to evaluate relationships with total amount of outdoor physical activity. After controlling for sex, race/ethnicity, skin color, and sun protection, regression analysis showed that each unit increase in perceived severity of nonmelanoma skin cancer was associated with a 30% increase in hours of outdoor physical activity (P = .005). Hours of outdoor physical activity were not related to perceived severity of melanoma or perceived susceptibility to skin cancer. BMI-for-age was not significantly correlated with perceptions of skin cancer threat, use of sun protection, or level of physical activity. The promotion of sun safety is not likely to inhibit physical activity. Skin cancer prevention programs should continue to promote midday sun avoidance and sun protection during outdoor activities.

Stellar activity with LAMOST - II. Chromospheric activity in open clusters

Science.gov (United States)

Fang, Xiang-Song; Zhao, Gang; Zhao, Jing-Kun; Bharat Kumar, Yerra

2018-05-01

We use the LAMOST spectra of member stars in Pleiades, M34, Praesepe, and Hyades to study how chromospheric activity varies as a function of mass and rotation at different age. We measured excess equivalent widths of H α, H β, and Ca II K based on estimated chromospheric contributions from old and inactive field dwarfs, and excess luminosities are obtained by normalizing bolometric luminosity, for more than 700 late-type stars in these open clusters. Results indicate two activity sequences in cool spot coverage and H α excess emission among GK dwarfs in Pleiades and M dwarfs in Praesepe and Hyades, paralleling with well-known rotation sequences. A weak dependence of chromospheric emission on rotation exists among ultrafast rotators in saturated regime with Rossby number Ro ≲ 0.1. In the unsaturated regime, chromospheric and coronal emission show similar dependence on Ro, but with a shift towards larger Ro, indicating chromospheric emission gets easily saturated than coronal emission, and/or convective turnover time-scales based on X-ray data do not work well with chromospheric emission. More interestingly, our analysis shows fully convective slow rotators obey the rotation-chromospheric activity relation similar to hotter stars, confirming the previous finding. We found correlations among H α, H β, and Ca II K emissions, in which H α losses are more important than Ca II K for cooler and more active stars. In addition, a weak correlation is seen between chromospheric emission and photospheric activity that shows dependence on stellar spectral type and activity level, which provides some clues on how spot configuration varies as a function of mass and activity level.

Hemoglobin–Albumin Cluster Incorporating a Pt Nanoparticle: Artificial O2 Carrier with Antioxidant Activities

Science.gov (United States)

Hosaka, Hitomi; Haruki, Risa; Yamada, Kana; Böttcher, Christoph; Komatsu, Teruyuki

2014-01-01

A covalent core–shell structured protein cluster composed of hemoglobin (Hb) at the center and human serum albumins (HSA) at the periphery, Hb-HSAm, is an artificial O2 carrier that can function as a red blood cell substitute. Here we described the preparation of a novel Hb-HSA3 cluster with antioxidant activities and its O2 complex stable in aqueous H2O2 solution. We used an approach of incorporating a Pt nanoparticle (PtNP) into the exterior HSA unit of the cluster. A citrate reduced PtNP (1.8 nm diameter) was bound tightly within the cleft of free HSA with a binding constant (K) of 1.1×107 M−1, generating a stable HSA-PtNP complex. This platinated protein showed high catalytic activities for dismutations of superoxide radical anions (O2 •–) and hydrogen peroxide (H2O2), i.e., superoxide dismutase and catalase activities. Also, Hb-HSA3 captured PtNP into the external albumin unit (K = 1.1×107 M−1), yielding an Hb-HSA3(PtNP) cluster. The association of PtNP caused no alteration of the protein surface net charge and O2 binding affinity. The peripheral HSA-PtNP shell prevents oxidation of the core Hb, which enables the formation of an extremely stable O2 complex, even in H2O2 solution. PMID:25310133

Association of proteasomal activity with metastasis in luminal breast cancer

Science.gov (United States)

Shashova, E. E.; Fesik, E. A.; Doroshenko, A. V.

2017-09-01

Chimotrypsin-like (ChTL) and caspase-like (CL) proteasomal activities were investigated in different variants of the tumor progression of luminal breast cancer. Patients with primary luminal breast cancer (n = 123) in stage T1-3N0-2M0 who had not received neoadjuvant treatment were included in this study. Proteasome ChTL and CL activities were determined in the samples of tumor and adjacent tissues. The coefficients of chymotrypsin-like (kChTL) and caspase-like (kCL) proteasome activity were also calculated as the ratio of the corresponding activity in the tumor tissue to activity in the adjacent tissue. ChTL, CL, kChTL and kCL in the tissues of luminal A and B breast cancer with lymphogenic metastasis were compared, and their association with hematogenous metastasis was evaluated. On the one hand, CL activity of proteasomes increased in luminal A breast cancer with extensive lymphogenic metastasis (N2), on the other hand it decreased in the luminal B subtype of cancer. The ratio of proteasomal activity in the tumor and adjacent tissues plays a significant role in the hematogenic pathway of breast cancer progression and is associated with poor metastatic-free survival.

Automated detection of microcalcification clusters in mammograms

Science.gov (United States)

Karale, Vikrant A.; Mukhopadhyay, Sudipta; Singh, Tulika; Khandelwal, Niranjan; Sadhu, Anup

2017-03-01

Mammography is the most efficient modality for detection of breast cancer at early stage. Microcalcifications are tiny bright spots in mammograms and can often get missed by the radiologist during diagnosis. The presence of microcalcification clusters in mammograms can act as an early sign of breast cancer. This paper presents a completely automated computer-aided detection (CAD) system for detection of microcalcification clusters in mammograms. Unsharp masking is used as a preprocessing step which enhances the contrast between microcalcifications and the background. The preprocessed image is thresholded and various shape and intensity based features are extracted. Support vector machine (SVM) classifier is used to reduce the false positives while preserving the true microcalcification clusters. The proposed technique is applied on two different databases i.e DDSM and private database. The proposed technique shows good sensitivity with moderate false positives (FPs) per image on both databases.

School‐based brief psycho‐educational intervention to raise adolescent cancer awareness and address barriers to medical help‐seeking about cancer: a cluster randomised controlled trial

Science.gov (United States)

Stoddart, Iona; Forbat, Liz; Neal, Richard D.; O'Carroll, Ronan E.; Haw, Sally; Rauchhaus, Petra; Kyle, Richard G.

2015-01-01

Abstract Objectives Raising cancer awareness and addressing barriers to help‐seeking may improve early diagnosis. The aim was to assess whether a psycho‐educational intervention increased adolescents' cancer awareness and addressed help‐seeking barriers. Methods This was a cluster randomised controlled trial involving 2173 adolescents in 20 schools. The intervention was a 50‐min presentation delivered by a member of Teenage Cancer Trust's (UK charity) education team. Schools were stratified by deprivation and roll size and randomly allocated to intervention/control conditions within these strata. Outcome measures were the number of cancer warning signs and cancer risk factors recognised, help‐seeking barriers endorsed and cancer communication. Communication self‐efficacy and intervention fidelity were also assessed. Results Regression models showed significant differences in the number of cancer warning signs and risk factors recognised between intervention and control groups. In intervention schools, the greatest increases in recognition of cancer warning signs at 6‐month follow‐up were for unexplained weight loss (from 44.2% to 62.0%) and change in the appearance of a mole (from 46.3% to 70.7%), up by 17.8% and 24.4%, respectively. Greatest increases in recognition of cancer risk factors were for getting sunburnt more than once as a child (from 41.0% to 57.6%) and being overweight (from 42.7% to 55.5%), up by 16.6% and 12.8%, respectively. Regression models showed that adolescents in intervention schools were 2.7 times more likely to discuss cancer at 2‐week follow‐up compared with the control group. No differences in endorsement of barriers to help‐seeking were observed. Conclusions School‐based brief psycho‐educational interventions are easy to deliver, require little resource and improve cancer awareness. © 2015 The Authors. Psycho‐Oncology published by John Wiley & Sons Ltd. PMID:26502987

School-based brief psycho-educational intervention to raise adolescent cancer awareness and address barriers to medical help-seeking about cancer: a cluster randomised controlled trial.

Science.gov (United States)

Hubbard, Gill; Stoddart, Iona; Forbat, Liz; Neal, Richard D; O'Carroll, Ronan E; Haw, Sally; Rauchhaus, Petra; Kyle, Richard G

2016-07-01

Raising cancer awareness and addressing barriers to help-seeking may improve early diagnosis. The aim was to assess whether a psycho-educational intervention increased adolescents' cancer awareness and addressed help-seeking barriers. This was a cluster randomised controlled trial involving 2173 adolescents in 20 schools. The intervention was a 50-min presentation delivered by a member of Teenage Cancer Trust's (UK charity) education team. Schools were stratified by deprivation and roll size and randomly allocated to intervention/control conditions within these strata. Outcome measures were the number of cancer warning signs and cancer risk factors recognised, help-seeking barriers endorsed and cancer communication. Communication self-efficacy and intervention fidelity were also assessed. Regression models showed significant differences in the number of cancer warning signs and risk factors recognised between intervention and control groups. In intervention schools, the greatest increases in recognition of cancer warning signs at 6-month follow-up were for unexplained weight loss (from 44.2% to 62.0%) and change in the appearance of a mole (from 46.3% to 70.7%), up by 17.8% and 24.4%, respectively. Greatest increases in recognition of cancer risk factors were for getting sunburnt more than once as a child (from 41.0% to 57.6%) and being overweight (from 42.7% to 55.5%), up by 16.6% and 12.8%, respectively. Regression models showed that adolescents in intervention schools were 2.7 times more likely to discuss cancer at 2-week follow-up compared with the control group. No differences in endorsement of barriers to help-seeking were observed. School-based brief psycho-educational interventions are easy to deliver, require little resource and improve cancer awareness. © 2015 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd. © 2015 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.

The Effect of Personal Characteristics, Perceived Threat, Efficacy and Breast Cancer Anxiety on Breast Cancer Screening Activation

Directory of Open Access Journals (Sweden)

Patrick De Pelsmacker

2017-09-01

Full Text Available In order to activate women to participate in breast cancer screening programs, a good understanding is needed of the personal characteristics that influence how women can be activated to search for more information, consult friends and doctors, and participate in breast cancer screening programs. In the current study, we investigate the effect of six personal characteristics that have in previous research been identified as important triggers of health behavior on breast cancer screening activation: Health awareness, Need for Cognition, Affect Intensity, Breast cancer knowledge, Topic involvement, and the Perceived breast cancer risk. We test the effect of these factors on four activation variables: intention of future information seeking, forwarding the message to a friend, talking to a doctor, and actual breast cancer screening attendance. Additionally, we try to unravel the process by means of which the antecedents (the six personal characteristics lead to activation. To that end, we test the mediating role of perceived breast cancer threat, perceived efficacy of screening, and the evoked breast cancer anxiety as mediators in this process. The data were collected by means of a cross-sectional survey in a sample of 700 Flemish (Belgium women who were invited to the free-of-charge breast cancer population screening. Screening attendance of this sample was provided by the government agency in charge of the organisation of the screening. Health awareness, affects intensity, topic involvement, and perceived risk have the strongest influence on activation. Breast cancer anxiety and perceived breast cancer threat have a substantial mediation effect on these effects. Efficacy perceptions are less important in the activation process. Increased health awareness and a higher level of perceived risk lead to less participation in the free of charge population based breast screening program. Implications for theory and practice are offered. The limitation

The Effect of Personal Characteristics, Perceived Threat, Efficacy and Breast Cancer Anxiety on Breast Cancer Screening Activation

Science.gov (United States)

De Pelsmacker, Patrick; Lewi, Martine; Cauberghe, Veroline

2017-01-01

In order to activate women to participate in breast cancer screening programs, a good understanding is needed of the personal characteristics that influence how women can be activated to search for more information, consult friends and doctors, and participate in breast cancer screening programs. In the current study, we investigate the effect of six personal characteristics that have in previous research been identified as important triggers of health behavior on breast cancer screening activation: Health awareness, Need for Cognition, Affect Intensity, Breast cancer knowledge, Topic involvement, and the Perceived breast cancer risk. We test the effect of these factors on four activation variables: intention of future information seeking, forwarding the message to a friend, talking to a doctor, and actual breast cancer screening attendance. Additionally, we try to unravel the process by means of which the antecedents (the six personal characteristics) lead to activation. To that end, we test the mediating role of perceived breast cancer threat, perceived efficacy of screening, and the evoked breast cancer anxiety as mediators in this process. The data were collected by means of a cross-sectional survey in a sample of 700 Flemish (Belgium) women who were invited to the free-of-charge breast cancer population screening. Screening attendance of this sample was provided by the government agency in charge of the organisation of the screening. Health awareness, affects intensity, topic involvement, and perceived risk have the strongest influence on activation. Breast cancer anxiety and perceived breast cancer threat have a substantial mediation effect on these effects. Efficacy perceptions are less important in the activation process. Increased health awareness and a higher level of perceived risk lead to less participation in the free of charge population based breast screening program. Implications for theory and practice are offered. The limitation of the study is

Effect of Water Clustering on the Activity of Candida antarctica Lipase B in Organic Medium

Directory of Open Access Journals (Sweden)

Sindrila Dutta Banik

2017-07-01

Full Text Available The effect of initial water activity of MTBE (methyl tert-butyl ether medium on CALB (Candida antarctica lipase B catalyzed esterification reaction is investigated using experimental methods and classical molecular dynamics (MD simulations. The experimental kinetic studies show that the initial reaction rate of CALB-catalyzed esterification reaction between butyric acid and ethanol decreases with increasing initial water activity of the medium. The highest rate of esterification is observed at the lowest water activity studied. MD simulations were performed to gain a molecular insight on the effect of initial water activity on the rate of CALB-catalyzed reaction. Our results show that hydration has an insignificant effect on the structure and flexibility of CALB. Rather, it appears that water molecules bind to certain regions (“hot spots” on the CALB surface and form clusters. The size of the water clusters at these hot spot regions gradually increase and expand with increasing water activity. Consequently, the surface area of CALB covered by the water molecules also increases. Specifically, our results indicate that a particular water cluster located close to the active site partially cover the binding pocket of substrate at high water activity. As a consequence, the effective concentration of substrate at the catalytic site decreases. Therefore, the reaction rate slows down with increasing water activity, which correlates well with the observed decrease in the experimentally determined initial reaction rate.

Apoptotic and Nonapoptotic Activities of Pterostilbene against Cancer

Directory of Open Access Journals (Sweden)

Rong-Jane Chen

2018-01-01

Full Text Available Cancer is a major cause of death. The outcomes of current therapeutic strategies against cancer often ironically lead to even increased mortality due to the subsequent drug resistance and to metastatic recurrence. Alternative medicines are thus urgently needed. Cumulative evidence has pointed out that pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene, PS has excellent pharmacological benefits for the prevention and treatment for various types of cancer in their different stages of progression by evoking apoptotic or nonapoptotic anti-cancer activities. In this review article, we first update current knowledge regarding tumor progression toward accomplishment of metastasis. Subsequently, we review current literature regarding the anti-cancer activities of PS. Finally, we provide future perspectives to clinically utilize PS as novel cancer therapeutic remedies. We, therefore, conclude and propose that PS is one ideal alternative medicine to be administered in the diet as a nutritional supplement.

Communication: CO oxidation by silver and gold cluster cations: Identification of different active oxygen species

International Nuclear Information System (INIS)

Popolan, Denisia M.; Bernhardt, Thorsten M.

2011-01-01

The oxidation of carbon monoxide with nitrous oxide on mass-selected Au 3 + and Ag 3 + clusters has been investigated under multicollision conditions in an octopole ion trap experiment. The comparative study reveals that for both gold and silver cations carbon dioxide is formed on the clusters. However, whereas in the case of Au 3 + the cluster itself acts as reactive species that facilitates the formation of CO 2 from N 2 O and CO, for silver the oxidized clusters Ag 3 O x + (n= 1-3) are identified as active in the CO oxidation reaction. Thus, in the case of the silver cluster cations N 2 O is dissociated and one oxygen atom is suggested to directly react with CO, whereas a second kind of oxygen strongly bound to silver is acting as a substrate for the reaction.

Communication: CO oxidation by silver and gold cluster cations: Identification of different active oxygen species

Science.gov (United States)

Popolan, Denisia M.; Bernhardt, Thorsten M.

2011-03-01

The oxidation of carbon monoxide with nitrous oxide on mass-selected Au3+ and Ag3+ clusters has been investigated under multicollision conditions in an octopole ion trap experiment. The comparative study reveals that for both gold and silver cations carbon dioxide is formed on the clusters. However, whereas in the case of Au3+ the cluster itself acts as reactive species that facilitates the formation of CO2 from N2O and CO, for silver the oxidized clusters Ag3Ox+ (n = 1-3) are identified as active in the CO oxidation reaction. Thus, in the case of the silver cluster cations N2O is dissociated and one oxygen atom is suggested to directly react with CO, whereas a second kind of oxygen strongly bound to silver is acting as a substrate for the reaction.

Dietary habits and physical activity patterns among Slovenian elderly: cross-sectional survey with cluster analysis

Directory of Open Access Journals (Sweden)

Joca Zurc

2015-03-01

Full Text Available Introduction: Physical activity and a healthy diet are significant predictors of healthy ageing—they help the elderly maintain their physical and mental health, and prevent chronic diseases. Methods: The data for the empirical quantitative survey were collected on the sample of 218 elderly community-dwelling participants (aged 65 years or more, using a structured questionnaire for self-reporting. Data analyses were proceed with the bivariate statistics, and multivariate hierarchical cluster analysis. Results: Most respondents reported good dietary habits (83.1% and a satisfactory physical activity level (60.5%. On average, the elderly eat 3-4 meals per day (59.8% and engage in physical activity at least three times a week (58.6%, with interventions lasting 15 minutes or more (84.4 % and non-organized activity prevailing (96.2%. Ward’s method yielded three clusters with homogenous dietary and physical activity patterns: ‘Health Conscious’ (30.8%, ‘At Risk’ (42.7% and ‘Special Requirements’ (26.5%. Significant differences were identified between clusters and educational level (p = 0.001. Discussion and conclusions: In the future, special attention should be placed on the elderly group with a lower educational level and special dietary and physical activity requirements. Additional studies on representative samples are required for a comprehensive investigation into the lifestyle behaviours of elderly individuals.

Sexual activity and the risk of prostate cancer: Review article

Directory of Open Access Journals (Sweden)

Ahmed Fouad Kotb

2015-09-01

Full Text Available Introduction: Sexual activity can affect prostate cancer pathogenesis in a variety of ways; including the proposed high androgen status, risk of sexually transmitted infections and the potential effect of retained carcinogens within the prostatic cells. Methods: PubMed review of all publications concerning sexual activity and the risk of prostate cancer was done by two researchers. Results: Few publications could be detected and data were classified as a prostate cancer risk in association with either heterosexual or homosexual activities. Conclusion: Frequent ejaculation seems to be protective from the development of prostate cancer. Multiple sexual partners may be protective from prostate cancer, excluding the risk of sexually transmitted infections. Homosexual men are at a greater risk for the diagnosis of prostate cancer.

Correlates and geographic patterns of knowledge that physical activity decreases cancer risk.

Science.gov (United States)

Ramírez, A Susana; Finney Rutten, Lila J; Vanderpool, Robin C; Moser, Richard P; Hesse, Bradford W

2013-04-01

While many lifestyle-related cancer risk factors including tobacco use, poor diet, and sun exposure are well recognized by the general public, the role of physical activity in decreasing cancer risk is less recognized. Studies have demonstrated gender-, race/ethnicity-, and age-based disparities in cancer risk factor knowledge; however, beliefs and geographic factors that may be related to knowledge are under-examined. In this study, we analyzed data from the 2008 Health Information National Trends Survey to determine correlates of knowledge of the relationship between physical activity and reduced cancer risk in the adult US population. We generated geographic information system maps to examine the geographic distribution of this knowledge. Results revealed that there is confusion among US adults about the relationship between physical activity and cancer risk: Respondents who believed that cancer is not preventable had significantly lower odds of knowing that physical activity reduces cancer risk (p physical activity reduces cancer risk (p physical activity guidelines were also significantly more likely to know that physical activity reduces cancer risk (p physical inactivity. Correlates of cancer risk factor knowledge point to opportunities for targeted interventions.

The role of extended Fe4S4 cluster ligands in mediating sulfite reductase hemoprotein activity.

Science.gov (United States)

Cepeda, Marisa R; McGarry, Lauren; Pennington, Joseph M; Krzystek, J; Elizabeth Stroupe, M

2018-05-28

The siroheme-containing subunit from the multimeric hemoflavoprotein NADPH-dependent sulfite reductase (SiR/SiRHP) catalyzes the six electron-reduction of SO 3 2- to S 2- . Siroheme is an iron-containing isobacteriochlorin that is found in sulfite and homologous siroheme-containing nitrite reductases. Siroheme does not work alone but is covalently coupled to a Fe 4 S 4 cluster through one of the cluster's ligands. One long-standing hypothesis predicted from this observation is that the environment of one iron-containing cofactor influences the properties of the other. We tested this hypothesis by identifying three amino acids (F437, M444, and T477) that interact with the Fe 4 S 4 cluster and probing the effect of altering them to alanine on the function and structure of the resulting enzymes by use of activity assays, X-ray crystallographic analysis, and EPR spectroscopy. We showed that F437 and M444 gate access for electron transfer to the siroheme-cluster assembly and the direct hydrogen bond between T477 and one of the cluster sulfides is important for determining the geometry of the siroheme active site. Copyright © 2018. Published by Elsevier B.V.

ISOTROPIC HEATING OF GALAXY CLUSTER CORES VIA RAPIDLY REORIENTING ACTIVE GALACTIC NUCLEUS JETS

International Nuclear Information System (INIS)

Babul, Arif; Sharma, Prateek; Reynolds, Christopher S.

2013-01-01

Active galactic nucleus (AGN) jets carry more than sufficient energy to stave off catastrophic cooling of the intracluster medium (ICM) in the cores of cool-core clusters. However, in order to prevent catastrophic cooling, the ICM must be heated in a near-isotropic fashion and narrow bipolar jets with P jet = 10 44–45 erg s –1 , typical of radio AGNs at cluster centers, are inefficient in heating the gas in the transverse direction to the jets. We argue that due to existent conditions in cluster cores, the supermassive black holes (SMBHs) will, in addition to accreting gas via radiatively inefficient flows, experience short stochastic episodes of enhanced accretion via thin disks. In general, the orientation of these accretion disks will be misaligned with the spin axis of the black holes (BHs) and the ensuing torques will cause the BH's spin axis (and therefore the jet axis) to slew and rapidly change direction. This model not only explains recent observations showing successive generations of jet-lobes-bubbles in individual cool-core clusters that are offset from each other in the angular direction with respect to the cluster center, but also shows that AGN jets can heat the cluster core nearly isotropically on the gas cooling timescale. Our model does require that the SMBHs at the centers of cool-core clusters be spinning relatively slowly. Torques from individual misaligned disks are ineffective at tilting rapidly spinning BHs by more than a few degrees. Additionally, since SMBHs that host thin accretion disks will manifest as quasars, we predict that roughly 1-2 rich clusters within z < 0.5 should have quasars at their centers.

Participation in Daily Life Activities among Children with Cancer

Directory of Open Access Journals (Sweden)

Ahmad Mohammadi

2017-09-01

Full Text Available Background: Participation in daily life activities is an essential aspect of health, which can facilitate a child’s development. Children with cancer are at risk of functional limitations and participation restrictions. The present study aims to investigate participation of children with cancer in daily life activities compared to healthy peers. Methods: This was a comparative cross-sectional study. In the first phase, we assessed the test-retest reliability of the Iranian Children Participation Assessment Scale in 30 children (6-12 years of age diagnosed with cancer and their parents (child and parent versions. The second phase of the study included a comparison of daily life activities as measured by the Iranian Children Participation Assessment Scale between the children with cancer (diagnosed at least 4 months prior and currently receiving active treatment and their age- and gender-matched healthy peers. Results: The child version had excellent reliability according to Cronbach’s alpha in diversity of activities (0.97, intensity of participation (0.95, with whom they participated (0.95, and enjoyment of daily activities (0.94. The parent version had excellent reliability (Cronbach’s alpha as follows: 0.99 for diversity, 0.97 for intensity, 0.97 for with whom, 0.98 for enjoyment, and 0.98 for parents’ satisfaction. The coefficients of agreement were 0.77 (total scores of diversity, 0.63 (intensity, 0.60 (with whom, and 0.91 (enjoyment. The child version indicated that children with cancer had significantly lower scores in daily life activities items of diversity (P=0.000, intensity (P=0.000, with whom (P=0.000, and enjoyment (P=0.000 compared to healthy children. Based on the total scores in the parent version, children with cancer showed significantly lower scores in diversity (P=0.001, intensity (P=0.000, with whom (P=0.001, enjoyment (P=0.002, and satisfaction (P=0.000 compared to the healthy group. Conclusion: The findings of the

Thermodynamics and proton activities of protic ionic liquids with quantum cluster equilibrium theory

Science.gov (United States)

Ingenmey, Johannes; von Domaros, Michael; Perlt, Eva; Verevkin, Sergey P.; Kirchner, Barbara

2018-05-01

We applied the binary Quantum Cluster Equilibrium (bQCE) method to a number of alkylammonium-based protic ionic liquids in order to predict boiling points, vaporization enthalpies, and proton activities. The theory combines statistical thermodynamics of van-der-Waals-type clusters with ab initio quantum chemistry and yields the partition functions (and associated thermodynamic potentials) of binary mixtures over a wide range of thermodynamic phase points. Unlike conventional cluster approaches that are limited to the prediction of thermodynamic properties, dissociation reactions can be effortlessly included into the bQCE formalism, giving access to ionicities, as well. The method is open to quantum chemical methods at any level of theory, but combination with low-cost composite density functional theory methods and the proposed systematic approach to generate cluster sets provides a computationally inexpensive and mostly parameter-free way to predict such properties at good-to-excellent accuracy. Boiling points can be predicted within an accuracy of 50 K, reaching excellent accuracy for ethylammonium nitrate. Vaporization enthalpies are predicted within an accuracy of 20 kJ mol-1 and can be systematically interpreted on a molecular level. We present the first theoretical approach to predict proton activities in protic ionic liquids, with results fitting well into the experimentally observed correlation. Furthermore, enthalpies of vaporization were measured experimentally for some alkylammonium nitrates and an excellent linear correlation with vaporization enthalpies of their respective parent amines is observed.

Surface activity, lipid profiles and their implications in cervical cancer.

Directory of Open Access Journals (Sweden)

Preetha A

2005-01-01

Full Text Available Background: The profiles of lipids in normal and cancerous tissues may differ revealing information about cancer development and progression. Lipids being surface active, changes in lipid profiles can manifest as altered surface activity profiles. Langmuir monolayers offer a convenient model for evaluating surface activity of biological membranes. Aims: The aims of this study were to quantify phospholipids and their effects on surface activity of normal and cancerous human cervical tissues as well as to evaluate the role of phosphatidylcholine (PC and sphingomyelin (SM in cervical cancer using Langmuir monolayers. Methods and Materials: Lipid quantification was done using thin layer chromatography and phosphorus assay. Surface activity was evaluated using Langmuir monolayers. Monolayers were formed on the surface of deionized water by spreading tissue organic phase corresponding to 1 mg of tissue and studying their surface pressure-area isotherms at body temperature. The PC and SM contents of cancerous human cervical tissues were higher than those of the normal human cervical tissues. Role of PC and SM were evaluated by adding varying amounts of these lipids to normal cervical pooled organic phase. Statistical analysis: Student′s t-test (p < 0.05 and one-way analysis of variance (ANOVA was used. Results: Our results reveals that the phosphatidylglycerol level in cancerous cervical tissue was nearly five folds higher than that in normal cervical tissue. Also PC and sphingomyelin SM were found to be the major phospholipid components in cancerous and normal cervical tissues respectively. The addition of either 1.5 µg DPPC or 0.5 µg SM /mg of tissue to the normal organic phase changed its surface activity profile to that of the cancerous tissues. Statistically significant surface activity parameters showed that PC and SM have remarkable roles in shifting the normal cervical lipophilic surface activity towards that of cancerous lipophilic

Clustering of diet, physical activity and smoking and a general willingness to change.

Science.gov (United States)

de Vries, Hein; Kremers, Stef; Smeets, Tamara; Reubsaet, Astrid

2008-01-01

Addressing multiple health behaviours are important in preventing disease and mortality. The present study investigated the clustering of health behaviours, cognitive determinants and stages of change in 2827 adults for the lifestyle factors of physical activity, fruit, vegetable and fat consumption and smoking. The results showed that only 3% of the total population met recommended guidelines for all of the five behaviours. Behaviours were found to be weakly associated. Behaviour-specific cognitions and stages of change for the behaviours clustered more strongly, however. With respect to diet and physical activity, respondents in the preparation stage for one behaviour were likely also to be preparing to change another behaviour. Possible mechanisms for the apparent general willingness to change multiple behaviours are discussed, as well as potential implications for health promotion practice.

Clustering of Sun Exposure Measurements

DEFF Research Database (Denmark)

Have, Anna Szynkowiak; Larsen, Jan; Hansen, Lars Kai

2002-01-01

In a medically motivated Sun-exposure study, questionnaires concerning Sun-habits were collected from a number of subjects together with UV radiation measurements. This paper focuses on identifying clusters in the heterogeneous set of data for the purpose of understanding possible relations between...... Sun-habits exposure and eventually assessing the risk of skin cancer. A general probabilistic framework originally developed for text and Web mining is demonstrated to be useful for clustering of behavioral data. The framework combines principal component subspace projection with probabilistic...

Motivations associated with physical activity in young breast cancer survivors.

Science.gov (United States)

Voege, Patricia; Bower, Julienne E; Stanton, Annette L; Ganz, Patricia A

2015-01-01

Physical activity is associated with positive health outcomes in breast cancer survivors. However, factors that promote or discourage physical activity in this population are not fully understood. This cross-sectional study was designed to examine approach and avoidance motivations, barriers for exercise, and their association with physical activity in breast cancer survivors younger than 50 years old at time of diagnosis. Current physical activity levels, approach and avoidance motivations, and barriers to exercise were assessed through self-report questionnaires in young breast cancer survivors (N = 156). Results indicated that barriers to exercise were negatively associated with physical activity (p physical activity (p barriers (p physical activity (p = .91).

Role of physical activity and diet after colorectal cancer diagnosis.

Science.gov (United States)

Van Blarigan, Erin L; Meyerhardt, Jeffrey A

2015-06-01

This review summarizes the evidence regarding physical activity and diet after colorectal cancer diagnosis in relation to quality of life, disease recurrence, and survival. There have been extensive reports on adiposity, inactivity, and certain diets, particularly those high in red and processed meats, and increased risk of colorectal cancer. Only in the past decade have data emerged on how such lifestyle factors are associated with outcomes in colorectal cancer survivors. Prospective observational studies have consistently reported that physical activity after colorectal cancer diagnosis reduces mortality. A meta-analysis estimated that each 15 metabolic equivalent task-hour per week increase in physical activity after colorectal cancer diagnosis was associated with a 38% lower risk of mortality. No randomized controlled trials have been completed to confirm that physical activity lowers risk of mortality among colorectal cancer survivors; however, trials have shown that physical activity, including structured exercise, is safe for colorectal cancer survivors (localized to metastatic stage, during and after treatment) and improves cardiorespiratory fitness and physical function. In addition, prospective observational studies have suggested that a Western dietary pattern, high carbohydrate intake, and consuming sugar-sweetened beverages after diagnosis may increase risk of colorectal cancer recurrence and mortality, but these data are limited to single analyses from one of two US cohorts. Additional data from prospective studies and randomized controlled trials are needed. Nonetheless, on the basis of the available evidence, it is reasonable to counsel colorectal cancer survivors to engage in regular physical activity and limit consumption of refined carbohydrates, red and processed meats, and sugar-sweetened beverages. © 2015 by American Society of Clinical Oncology.

Physical activity influences the immune system of breast cancer patients

Directory of Open Access Journals (Sweden)

Thorsten Schmidt

2017-01-01

Full Text Available It has been suggested that physical activity in breast cancer patients can not only improve quality of life. Influences on physical and psychological levels have been evaluated, but effects on the immune system of breast cancer patients are hardly known. A PubMed search identified relevant trials and meta-analyses from 1970 to 2013. This review summarizes the results of international studies and the current discussion of effects of physical activity on the immune system of breast cancer patients. Highlighted are effects of physical activity on the immune system. Seven original articles and 14 reviews included in this review. Two original and the review articles includes other tumor entities besides breast cancer.Evaluated methods such as dose-response relationships for exercise in oncology, hardly exist. Increased immunological anti-cancer activity due to physical activity is probably mediated via an increase in number and cytotoxicity of monocytes and natural killer cells and cytokines.

Size and Site Dependence of the Catalytic Activity of Iridium Clusters toward Ethane Dehydrogenation.

Science.gov (United States)

Ge, Yingbin; Jiang, Hao; Kato, Russell; Gummagatta, Prasuna

2016-12-01

This research focuses on optimizing transition metal nanocatalyst immobilization and activity to enhance ethane dehydrogenation. Ethane dehydrogenation, catalyzed by thermally stable Ir n (n = 8, 12, 18) atomic clusters that exhibit a cuboid structure, was studied using the B3LYP method with triple-ζ basis sets. Relativistic effects and dispersion corrections were included in the calculations. In the dehydrogenation reaction Ir n + C 2 H 6 → H-Ir n -C 2 H 5 → (H) 2 -Ir n -C 2 H 4 , the first H-elimination is the rate-limiting step, primarily because the reaction releases sufficient heat to facilitate the second H-elimination. The catalytic activity of the Ir clusters strongly depends on the Ir cluster size and the specific catalytic site. Cubic Ir 8 is the least reactive toward H-elimination in ethane: Ir 8 + C 2 H 6 → H-Ir 8 -C 2 H 5 has a large (65 kJ/mol) energy barrier, whereas Ir 12 (3 × 2 × 2 cuboid) and Ir 18 (3 × 3 × 2 cuboid) lower this energy barrier to 22 and 3 kJ/mol, respectively. The site dependence is as prominent as the size effect. For example, the energy barrier for the Ir 18 + C 2 H 6 → H-Ir 18 -C 2 H 5 reaction is 3, 48, and 71 kJ/mol at the corner, edge, or face-center sites of the Ir 18 cuboid, respectively. Energy release due to Ir cluster insertion into an ethane C-H bond facilitates hydrogen migration on the Ir cluster surface, and the second H-elimination of ethane. In an oxygen-rich environment, oxygen molecules may be absorbed on the Ir cluster surface. The oxygen atoms bonded to the Ir cluster surface may slightly increase the energy barrier for H-elimination in ethane. However, the adsorption of oxygen and its reaction with H atoms on the Ir cluster releases sufficient heat to yield an overall thermodynamically favored reaction: Ir n + C 2 H 6 + 1 / 2 O 2 → Ir n + C 2 H 4 + H 2 O. These results will be useful toward reducing the energy cost of ethane dehydrogenation in industry.

THE EVOLUTION OF ACTIVE GALACTIC NUCLEI IN CLUSTERS OF GALAXIES TO REDSHIFT 1.3

International Nuclear Information System (INIS)

Martini, Paul; Sivakoff, Gregory R.; Mulchaey, John S.

2009-01-01

We have measured the luminous active galactic nucleus (AGN) population in a large sample of clusters of galaxies and find evidence for a substantial increase in the cluster AGN population from z ∼ 0.05 to z ∼ 1.3. The present sample now includes 32 clusters of galaxies, including 15 clusters above z = 0.4, which corresponds to a three-fold increase compared to our previous work at high redshift. At z R R (z) + 1 that host AGNs with rest-frame, hard X-ray [2-10 keV] luminosities L X,H ≥ 10 43 erg s -1 . The AGN fraction increases from f A = 0.134 +0.18 -0.087 % at a median z = 0.19 to f A = 1.00 +0.29 -0.23 % at a median z = 0.72. Our best estimate of the evolution is a factor of 8 increase to z = 1 and the statistical significance of the increase is 3.8σ. This dramatic evolution is qualitatively similar to the evolution of the star-forming galaxy population in clusters known as the Butcher-Oemler effect. We discuss the implications of this result for the coevolution of black holes and galaxies in clusters, the evolution of AGN feedback, searches for clusters with the Sunyaev-Zel'dovich effect, and the possible detection of environment-dependent downsizing.

Pain management in cancer center inpatients: a cluster randomized trial to evaluate a systematic integrated approach—The Edinburgh Pain Assessment and Management Tool

OpenAIRE

Fallon, M; Walker, J; Colvin, L; Rodriguez, A; Murray, G; Sharpe, M

2018-01-01

Purpose Pain is suboptimally managed in patients with cancer. We aimed to compare the effect of a policy of adding a clinician-delivered bedside pain assessment and management tool (Edinburgh Pain Assessment and management Tool [EPAT]) to usual care (UC) versus UC alone on pain outcomes. Patients and Methods In a two-arm, parallel group, cluster randomized (1:1) trial, we observed pain outcomes in 19 cancer centers in the United Kingdom and then randomly assigned the centers to eithe...

A clustering model proposal for activity optimization vs. image quality. Application in HMPAO-99mTc brain SPECT

International Nuclear Information System (INIS)

Perez, M.; Diaz, O.; Estevez, E.; Roque, R.; Hernandez, C.

2008-01-01

A method based on clustering analysis and image quality discriminant functions is tested over HMPAO- 99m Tc -SPECT images to optimize image quality vs. administered activity to patient. Signal-to-Noise ratios and Signal-to-Background ratios in each transaxial slice were measured over the images and used as image quality objective indexes. They were employed to develop image quality classification using a model of three clusters (k-mean Cluster Technique). The mathematical classification was compared with the subjective image quality evaluation, following expert observer criterion. Linear image quality discrimination was developed using the results of the cluster classification and taking as independent variables: the characteristics of the patients (sex, age and weight) and the radiopharmaceutical (labelling yield and administered activity). The dependent variables in the discriminant functions were the cluster centroids. The objective of this procedure was assigning a statistical weight to each image quality determinant variable for the optimization purpose. The method was applied in 30 brain SPECT images, acquired under different activities (400 MBq, 600 MBq, 800 MBq and 1000 MBq as reference), with a Sopha gamma camera, mean-resolution - general purpose - parallel-hole collimator, acquisition matrix 128 x 128 pixels and reconstruction following Filter - Back - Projection Algorithm. We looked for the minimum activity that guaranty most of the cases classified into the cluster with the best image quality (optimization criterion). The value of 800 MBq was the optimum obtained after application of the above methodology for the technology used. The labelling yield and the weight of the patients were the main parameters which determined image quality in clusters, as well as the processing digital filter used. The reduction in the effective dose, as a consequence of this procedure implementation, was also analysed. (author)

NAC selectively inhibit cancer telomerase activity: A higher redox homeostasis threshold exists in cancer cells

Directory of Open Access Journals (Sweden)

Pengying Li

2016-08-01

Full Text Available Telomerase activity controls telomere length, and this plays an important role in stem cells, aging and tumors. Antioxidant was shown to protect telomerase activity in normal cells but inhibit that in cancer cells, but the underlying mechanism is elusive. Here we found that 7721 hepatoma cells held a higher redox homeostasis threshold than L02 normal liver cells which caused 7721 cells to have a higher demand for ROS; MnSOD over-expression in 7721 decreased endogenous reactive oxygen species (ROS and inhibited telomerase activity; Akt phosphorylation inhibitor and NAC both inhibited 7721 telomerase activity. The over-elimination of ROS by NAC resulted in the inhibition of Akt pathway. Our results suggest that ROS is involved in the regulation of cancer telomerase activity through Akt pathway. The different intracellular redox homeostasis and antioxidant system in normal cells and tumor cells may be the cause of the opposite effect on telomerase activity in response to NAC treatment. Our results provide a theoretical base of using antioxidants selectively inhibit cancer telomerase activity. Findings of the present study may provide insights into novel approaches for cancer treatment.

Magnetic resonance imaging with k-means clustering objectively measures whole muscle volume compartments in sarcopenia/cancer cachexia.

Science.gov (United States)

Gray, Calum; MacGillivray, Thomas J; Eeley, Clare; Stephens, Nathan A; Beggs, Ian; Fearon, Kenneth C; Greig, Carolyn A

2011-02-01

Sarcopenia and cachexia are characterized by infiltration of non-contractile tissue within muscle which influences area and volume measurements. We applied a statistical clustering (k-means) technique to magnetic resonance (MR) images of the quadriceps of young and elderly healthy women and women with cancer to objectively separate the contractile and non-contractile tissue compartments. MR scans of the thigh were obtained for 34 women (n = 16 young, (median) age 26 y; n = 9 older, age 80 y; n = 9 upper gastrointestinal cancer patients, age 65 y). Segmented regions of consecutive axial images were used to calculate cross-sectional area and (gross) volume. The k-means unsupervised algorithm was subsequently applied to the MR binary mask image array data with resultant volumes compared between groups. Older women and women with cancer had 37% and 48% less quadriceps muscle respectively than young women (p k-means subtracted a significant 9%, 14% and 20% non-contractile tissue from the quadriceps of young, older and patient groups respectively (p K-means objectively separates contractile and non-contractile tissue components. Women with upper GI cancer have significant fatty infiltration throughout whole muscle groups which is maintained when controlling for age. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The clustering of diet, physical activity and sedentary behavior in children and adolescents: a review.

Science.gov (United States)

Leech, Rebecca M; McNaughton, Sarah A; Timperio, Anna

2014-01-22

Diet, physical activity (PA) and sedentary behavior are important, yet modifiable, determinants of obesity. Recent research into the clustering of these behaviors suggests that children and adolescents have multiple obesogenic risk factors. This paper reviews studies using empirical, data-driven methodologies, such as cluster analysis (CA) and latent class analysis (LCA), to identify clustering patterns of diet, PA and sedentary behavior among children or adolescents and their associations with socio-demographic indicators, and overweight and obesity. A literature search of electronic databases was undertaken to identify studies which have used data-driven methodologies to investigate the clustering of diet, PA and sedentary behavior among children and adolescents aged 5-18 years old. Eighteen studies (62% of potential studies) were identified that met the inclusion criteria, of which eight examined the clustering of PA and sedentary behavior and eight examined diet, PA and sedentary behavior. Studies were mostly cross-sectional and conducted in older children and adolescents (≥ 9 years). Findings from the review suggest that obesogenic cluster patterns are complex with a mixed PA/sedentary behavior cluster observed most frequently, but healthy and unhealthy patterning of all three behaviors was also reported. Cluster membership was found to differ according to age, gender and socio-economic status (SES). The tendency for older children/adolescents, particularly females, to comprise clusters defined by low PA was the most robust finding. Findings to support an association between obesogenic cluster patterns and overweight and obesity were inconclusive, with longitudinal research in this area limited. Diet, PA and sedentary behavior cluster together in complex ways that are not well understood. Further research, particularly in younger children, is needed to understand how cluster membership differs according to socio-demographic profile. Longitudinal research is

Physical activity and the risk of colorectal cancer in Lynch syndrome.

Science.gov (United States)

Dashti, S Ghazaleh; Win, Aung Ko; Hardikar, Sheetal S; Glombicki, Stephen E; Mallenahalli, Sheila; Thirumurthi, Selvi; Peterson, Susan K; You, Y Nancy; Buchanan, Daniel D; Figueiredo, Jane C; Campbell, Peter T; Gallinger, Steven; Newcomb, Polly A; Potter, John D; Lindor, Noralane M; Le Marchand, Loic; Haile, Robert W; Hopper, John L; Jenkins, Mark A; Basen-Engquist, Karen M; Lynch, Patrick M; Pande, Mala

2018-06-14

Greater physical activity is associated with a decrease in risk of colorectal cancer for the general population; however, little is known about its relationship with colorectal cancer risk for people with Lynch syndrome, carriers of inherited pathogenic mutations in genes affecting DNA mismatch repair (MMR). We studied a cohort of 2,042 MMR gene mutations carriers (n=807, diagnosed with colorectal cancer), from the Colon Cancer Family Registry. Self-reported physical activity in three age-periods (20-29, 30-49, and ≥50 years) was summarized as average metabolic equivalent of task hours per week (MET-h/week) during the age-period of cancer diagnosis or censoring (near-term exposure), and across all age-periods preceding cancer diagnosis or censoring (long-term exposure). Weighted Cox regression was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) for the association between physical activity and colorectal cancer risk. Near-term physical activity was associated with a small reduction in the risk of colorectal cancer (HR ≥35 vs. Lynch syndrome, however, further confirmation is warranted. The potential modifying effect of physical activity on colorectal cancer risk for people with Lynch syndrome could be useful for risk prediction and support counseling advice for lifestyle modification to reduce cancer risk. This article is protected by copyright. All rights reserved. © 2018 UICC.

Irradiation and various cytotoxic drugs enhance tyrosine phosphorylation and β1-integrin clustering in human A549 lung cancer cells in a substratum-dependent manner in vitro

International Nuclear Information System (INIS)

Cordes, N.; Beinke, C.; Beuningen, D. van; Plasswilm, L.

2004-01-01

Background and purpose: interactions of cells with a substratum, especially extracellular matrix proteins, initiate clustering of integrin receptors in the cell membrane. This process represents the initial step for the activation of signaling pathways regulating survival, proliferation, differentiation, adhesion, and migration, and could, furthermore, be important for cellular resistance-mediating mechanisms against radiation or cytotoxic drugs. The lack of data elucidating the impact of irradiation or cytotoxic drugs on this important phenomenon led to this study on human A549 lung cancer cells in vitro. Material and methods: the human lung carcinoma cell line A549 grown on polystyrene or fibronectin (FN) was irradiated with 0-8 Gy or treated with cisplatin (0.1-50 μM), paclitaxel (0.1-50 nM), or mitomycin (0.1-50 μM). Colony formation assays, immunofluorescence staining in combination with activation of integrin clustering using anti-β 1 -integrin antibodies (K20), and Western blotting for tyrosine phosphorylation under treatment of cells with the IC 50 for irradiation (2 Gy; IC 50 = 2.2 Gy), cisplatin (2 μM), paclitaxel (5 nM), or mitomycin (7 μM) were performed. Results: attachment of cells to FN resulted in a significantly reduced radio- and chemosensitivity compared to polystyrene. The clustering of β 1 -integrins examined by immunofluorescence staining was only stimulated by irradiation, cisplatin, paclitaxel, or mitomycin in case of cell attachment to FN. By contrast, tyrosine phosphorylation, as one of the major events following β 1 -integrin clustering, showed a 3.7-fold, FN-related enhancement, and treatment of cells with the IC 50 of radiation, cisplatin, paclitaxel, or mitomycin showed a substratum-dependent induction. Conclusion: for the first time, a strong influence of irradiation and a variety of cytotoxic drugs on the clustering of β 1 -integrins could be shown. This event is a prerequisite for tyrosine phosphorylation and, thus, the

Student profiling on university co-curricular activities using cluster analysis

Science.gov (United States)

Rajenthran, Hemabegai A./P.; Shaharanee, Izwan Nizal Mohd; Jamil, Jastini Mohd.

2017-11-01

In higher learning institutions, the co-curricular programs are needed for the graduation besides the standard academic programs. By actively participating in co-curricular, students can attain many of soft skills and proficiencies besides learning and adopting campus environment, community and traditions. Co-curricular activities are implemented by universities mainly for the refinement of the academic achievement along with the social development. This studies aimed to analyse the academic profile of the co-curricular students among uniform units. The main objective of study is to develop a profile of student co-curricular activities in uniform units. Additionally, several variables has been selected to serve as the characteristics for student co-curricular profile. The findings of this study demonstrate the practicality of clustering technique to investigate student's profiles and allow for a better understanding of student's behavior and co-curriculum activities.

A nonparametric Bayesian approach for clustering bisulfate-based DNA methylation profiles.

Science.gov (United States)

Zhang, Lin; Meng, Jia; Liu, Hui; Huang, Yufei

2012-01-01

DNA methylation occurs in the context of a CpG dinucleotide. It is an important epigenetic modification, which can be inherited through cell division. The two major types of methylation include hypomethylation and hypermethylation. Unique methylation patterns have been shown to exist in diseases including various types of cancer. DNA methylation analysis promises to become a powerful tool in cancer diagnosis, treatment and prognostication. Large-scale methylation arrays are now available for studying methylation genome-wide. The Illumina methylation platform simultaneously measures cytosine methylation at more than 1500 CpG sites associated with over 800 cancer-related genes. Cluster analysis is often used to identify DNA methylation subgroups for prognosis and diagnosis. However, due to the unique non-Gaussian characteristics, traditional clustering methods may not be appropriate for DNA and methylation data, and the determination of optimal cluster number is still problematic. A Dirichlet process beta mixture model (DPBMM) is proposed that models the DNA methylation expressions as an infinite number of beta mixture distribution. The model allows automatic learning of the relevant parameters such as the cluster mixing proportion, the parameters of beta distribution for each cluster, and especially the number of potential clusters. Since the model is high dimensional and analytically intractable, we proposed a Gibbs sampling "no-gaps" solution for computing the posterior distributions, hence the estimates of the parameters. The proposed algorithm was tested on simulated data as well as methylation data from 55 Glioblastoma multiform (GBM) brain tissue samples. To reduce the computational burden due to the high data dimensionality, a dimension reduction method is adopted. The two GBM clusters yielded by DPBMM are based on data of different number of loci (P-value < 0.1), while hierarchical clustering cannot yield statistically significant clusters.

Improvement of pain-related self-management for cancer patients through a modular transitional nursing intervention: a cluster-randomized multicenter trial.

Science.gov (United States)

Jahn, Patrick; Kuss, Oliver; Schmidt, Heike; Bauer, Alexander; Kitzmantel, Maria; Jordan, Karin; Krasemann, Susann; Landenberger, Margarete

2014-04-01

Patients' self-management skills are affected by their knowledge, activities, and attitudes toward pain management. This trial aimed to test the Self Care Improvement through Oncology Nursing (SCION)-PAIN program, a multimodular structured intervention to reduce patients' barriers to self-management of cancer pain. Two hundred sixty-three patients with diagnosed malignancy, pain>3 days, and average pain > or = 3/10 participated in a cluster-randomized trial on 18 wards in 2 German university hospitals. Patients on the intervention wards received, in addition to standard pain treatment, the SCION-PAIN program consisting of 3 modules: pharmacologic, nonpharmacologic pain management, and discharge management. The intervention was conducted by specially trained cancer nurses and included components of patient education, skills training, and counseling. Starting with admission, patients received booster sessions every third day and one follow-up telephone counseling session within 2 to 3 days after discharge. Patients in the control group received standard care. Primary end point was the group difference in patient-related barriers to self-management of cancer pain (Barriers Questionnaire-BQ II) 7 days after discharge. The SCION-PAIN program resulted in a significant reduction of patient-related barriers to pain management 1 week after discharge from the hospital: mean difference on BQ II was -0.49 points (95% confidence interval -0.87 points to -0.12 points; P=0.02). Furthermore, patients showed improved adherence to pain medication; odds ratio 8.58 (95% confidence interval 1.66-44.40; P=0.02). A post hoc analysis indicated reduced average and worst pain intensity as well as improved quality of life. This trial reveals the positive impact of a nursing intervention to improve patients' self-management of cancer pain. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

The WHO activities on thyroid cancer

International Nuclear Information System (INIS)

Baverstock, K.; Cardis, E.

1996-01-01

The WHO has been involved in activities related to thyroid disease in populations exposed to Chernobyl fallout since 1991. The International Programme on the Health Effects of the Chernobyl Accident, based in Geneva, undertook a pilot project on screening for thyroid disease and the WHO European Centre for Environment and Health responded to claims from Belarus of an increase of childhood thyroid cancer. Since then the WHO has been developing the public health response in partnership with scientists and physicians in Belarus and a number of centres of excellence outside the CIS specializing in the disciplines relevant to the problem. In 1993 the International Thyroid Project was initiated in partnership with the International Agency for Cancer Research. The activities developed with scientists and physicians in Belarus to respond to the increase are described. The increase in thyroid cancer and its implications for future accidents have been addressed. Revised advice on stable iodine prophylaxis has been formulated

Physical Activity, Biomarkers, and Disease Outcomes in Cancer Survivors: A Systematic Review

Science.gov (United States)

Friedenreich, Christine M.; Courneya, Kerry S.; Siddiqi, Sameer M.; McTiernan, Anne; Alfano, Catherine M.

2012-01-01

Background Cancer survivors often seek information about how lifestyle factors, such as physical activity, may influence their prognosis. We systematically reviewed studies that examined relationships between physical activity and mortality (cancer-specific and all-cause) and/or cancer biomarkers. Methods We identified 45 articles published from January 1950 to August 2011 through MEDLINE database searches that were related to physical activity, cancer survival, and biomarkers potentially relevant to cancer survival. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement to guide this review. Study characteristics, mortality outcomes, and biomarker-relevant and subgroup results were abstracted for each article that met the inclusion criteria (ie, research articles that included participants with a cancer diagnosis, mortality outcomes, and an assessment of physical activity). Results There was consistent evidence from 27 observational studies that physical activity is associated with reduced all-cause, breast cancer–specific, and colon cancer–specific mortality. There is currently insufficient evidence regarding the association between physical activity and mortality for survivors of other cancers. Randomized controlled trials of exercise that included biomarker endpoints suggest that exercise may result in beneficial changes in the circulating level of insulin, insulin-related pathways, inflammation, and, possibly, immunity; however, the evidence is still preliminary. Conclusions Future research directions identified include the need for more observational studies on additional types of cancer with larger sample sizes; the need to examine whether the association between physical activity and mortality varies by tumor, clinical, or risk factor characteristics; and the need for research on the biological mechanisms involved in the association between physical activity and survival after a cancer diagnosis. Future randomized

Changing ionization conditions in SDSS galaxies with active galactic nuclei as a function of environment from pairs to clusters

International Nuclear Information System (INIS)

Khabiboulline, Emil T.; Steinhardt, Charles L.; Silverman, John D.; Ellison, Sara L.; Mendel, J. Trevor; Patton, David R.

2014-01-01

We study how active galactic nucleus (AGN) activity changes across environments from galaxy pairs to clusters using 143,843 galaxies with z < 0.2 from the Sloan Digital Sky Survey. Using a refined technique, we apply a continuous measure of AGN activity, characteristic of the ionization state of the narrow-line emitting gas. Changes in key emission-line ratios ([N II] λ6548/Hα, [O III] λ5007/Hβ) between different samples allow us to disentangle different environmental effects while removing contamination. We confirm that galaxy interactions enhance AGN activity. However, conditions in the central regions of clusters are inhospitable for AGN activity even if galaxies are in pairs. These results can be explained through models of gas dynamics in which pair interactions stimulate the transfer of gas to the nucleus and clusters suppress gas availability for accretion onto the central black hole.

Changing ionization conditions in SDSS galaxies with active galactic nuclei as a function of environment from pairs to clusters

Energy Technology Data Exchange (ETDEWEB)

Khabiboulline, Emil T.; Steinhardt, Charles L. [California Institute of Technology, 1200 East-California Boulevard, Pasadena, CA 91125 (United States); Silverman, John D. [Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo, Kashiwanoha 5-1-5, Kashiwa-Shi, Chiba 277-8583 (Japan); Ellison, Sara L. [Department of Physics and Astronomy, University of Victoria, Finnerty Road, Victoria, British Columbia, V8P 1A1 (Canada); Mendel, J. Trevor [Max Planck Institute for Extraterrestrial Physics, Giessenbachstrasse, D-85748 Garching (Germany); Patton, David R., E-mail: ekhabibo@caltech.edu [Department of Physics and Astronomy, Trent University, 1600 West Bank Drive, Peterborough, Ontario, K9J 7B8 (Canada)

2014-11-01

We study how active galactic nucleus (AGN) activity changes across environments from galaxy pairs to clusters using 143,843 galaxies with z < 0.2 from the Sloan Digital Sky Survey. Using a refined technique, we apply a continuous measure of AGN activity, characteristic of the ionization state of the narrow-line emitting gas. Changes in key emission-line ratios ([N II] λ6548/Hα, [O III] λ5007/Hβ) between different samples allow us to disentangle different environmental effects while removing contamination. We confirm that galaxy interactions enhance AGN activity. However, conditions in the central regions of clusters are inhospitable for AGN activity even if galaxies are in pairs. These results can be explained through models of gas dynamics in which pair interactions stimulate the transfer of gas to the nucleus and clusters suppress gas availability for accretion onto the central black hole.

Active surveillance for clinically localized prostate cancer

DEFF Research Database (Denmark)

Thomsen, Frederik B; Brasso, Klaus; Klotz, Laurence H

2014-01-01

Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection for the AS stra......Active surveillance (AS) has been introduced as an observational strategy to delay or avoid curative treatment without compromising long-term cancer-specific survival. The 10 studies included in this review, published between 2008 and 2013, generally agreed upon patients selection...

Anti-cancer activity of compounds from Bauhinia strychnifolia stem.

Science.gov (United States)

Yuenyongsawad, Supreeya; Bunluepuech, Kingkan; Wattanapiromsakul, Chatchai; Tewtrakul, Supinya

2013-11-25

The stem and root of Bauhinia strychnifolia Craib (Fabaceae family) have been traditionally used in Thailand to treat fever, alcoholic toxication, allergy and cancer. An EtOH extract of Bauhinia strychnifolia showed good inhibitory activity against several cancer cell lines including HT-29, HeLa, MCF-7 and KB. As there has been no previous reports on chemical constituents of Bauhinia strychnifolia, this study is aimed to isolate the pure compounds with anti-cancer activity. Five pure compounds were isolated from EtOH extract of Bauhinia strychnifolia stem using silica gel, dianion HP-20 and sephadex LH-20 column chromatography and were tested for their cytotoxic effects against HT-29, HeLa, MCF-7 and KB cell lines using the Sulforhodamine B (SRB) assay. Among five compounds, 3,5,7,3',5'-pentahydroxyflavanonol-3-O-α-l-rhamnopyranoside (2) possessed very potent activity against KB (IC₅₀=0.00054μg/mL), HT-29 (IC₅₀=0.00217 μg/mL), MCF-7 (IC₅₀=0.0585 μg/mL) and HeLa cells (IC₅₀=0.0692 μg/mL). 3,5,7-Trihydroxychromone-3-O-α-l-rhamnopyranoside (3) also showed good activity against HT-29 (IC₅₀=0.02366 μg/mL), KB (IC₅₀=0.0412 μg/mL) and MCF-7 (IC₅₀=0.297 μg/mL), respectively. The activity of 2 (IC₅₀=0.00054 μg/mL) against KB cell was ten times higher than that of the positive control, Camptothecin (anti-cancer drug, IC₅₀=0.0057 μg/mL). All compounds did not show any cytotoxicity with normal cells at the concentration of 1 μg/mL. This is the first report of compounds 2 and 3 on anti-cancer activity and based on the anti-cancer activity of extracts and pure compounds isolated from Bauhinia strychnifolia stem, it might be suggested that this plant could be useful for treatment of cancer. © 2013 Elsevier Ireland Ltd. All rights reserved.

Physical activity in advanced cancer patients: a systematic review protocol.

Science.gov (United States)

Lowe, Sonya S; Tan, Maria; Faily, Joan; Watanabe, Sharon M; Courneya, Kerry S

2016-03-11

Progressive, incurable cancer is associated with increased fatigue, increased muscle weakness, and reduced physical functioning, all of which negatively impact quality of life. Physical activity has demonstrated benefits on cancer-related fatigue and physical functioning in early-stage cancer patients; however, its impact on these outcomes in end-stage cancer has not been established. The aim of this systematic review is to determine the potential benefits, harms, and effects of physical activity interventions on quality of life outcomes in advanced cancer patients. A systematic review of peer-reviewed literature on physical activity in advanced cancer patients will be undertaken. Empirical quantitative studies will be considered for inclusion if they present interventional or observational data on physical activity in advanced cancer patients. Searches will be conducted in the following electronic databases: CINAHL; CIRRIE Database of International Rehabilitation Research; Cochrane Database of Systematic Reviews (CDSR); Database of Abstracts of Reviews of Effects (DARE); Cochrane Central Register of Controlled Trials (CENTRAL); EMBASE; MEDLINE; PEDro: the Physiotherapy Evidence Database; PQDT; PsycInfo; PubMed; REHABDATA; Scopus; SPORTDiscus; and Web of Science, to identify relevant studies of interest. Additional strategies to identify relevant studies will include citation searches and evaluation of reference lists of included articles. Titles, abstracts, and keywords of identified studies from the search strategies will be screened for inclusion criteria. Two independent reviewers will conduct quality appraisal using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies (EPHPP) and the Cochrane risk of bias tool. A descriptive summary of included studies will describe the study designs, participant and activity characteristics, and objective and patient-reported outcomes. This systematic review will summarize the current

Plasma-activated medium (PAM) kills human cancer-initiating cells.

Science.gov (United States)

Ikeda, Jun-Ichiro; Tanaka, Hiromasa; Ishikawa, Kenji; Sakakita, Hajime; Ikehara, Yuzuru; Hori, Masaru

2018-01-01

Medical non-thermal plasma (NTP) treatments for various types of cancers have been reported. Cells with tumorigenic potential (cancer-initiating cells; CICs) are few in number in many types of tumors. CICs efficiently eliminate anti-cancer chemicals and exhibit high-level aldehyde dehydrogenase (ALDH) activity. We previously examined the effects of direct irradiation via NTP on cancer cells; even though we targeted CICs expressing high levels of ALDH, such treatment affected both non-CICs and CICs. Recent studies have shown that plasma-activated medium (PAM) (culture medium irradiated by NTP) selectively induces apoptotic death of cancer but not normal cells. Therefore, we explored the anti-cancer effects of PAM on CICs among endometrioid carcinoma and gastric cancer cells. PAM reduced the viability of cells expressing both low and high levels of ALDH. Combined PAM/cisplatin appeared to kill cancer cells more efficiently than did PAM or cisplatin alone. In a mouse tumor xenograft model, PAM exerted an anti-cancer effect on CICs. Thus, our results suggest that PAM effectively kills both non-CICs and CICs, as does NTP. Therefore, PAM may be a useful new anti-cancer therapy, targeting various cancer cells including CICs. © 2017 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Nutrition habits, physical activity, and lung cancer: an authoritative review.

Science.gov (United States)

Koutsokera, Alexandra; Kiagia, Maria; Saif, Muhammad W; Souliotis, Kyriakos; Syrigos, Kostas N

2013-07-01

Lung cancer is the leading cause of cancer death worldwide. Because of high incidence rates and low survival rates, it is important to study the risk factors that may help prevent the disease from developing. It has been well established that cigarette smoking is the most important risk factor for lung cancer. Nonetheless it is likely that there are other modifiable risk factors that would assist in the prevention of lung cancer. Research on factors such as nutrition and physical activity and their influence on lung cancer has been carried out for nearly 3 decades. A systematic review in the MEDLINE database of published studies was conducted, focusing on systematic reviews, meta-analyses, and large prospective studies. The association between physical activity and lung cancer has been conflicting. Among the researched studies, 10 showed an inverse association, whereas 11 reported no association. A meta-analysis that was conducted from 1996 to October 2003 showed that leisure physical activity (LPA) prevents lung cancer. Data from 11 cohort and case-control studies showed an inverse relationship between fruit and vegetable consumption and lung cancer. Evidence from case-control studies suggests a positive association between meat intake and risk of lung cancer, although several more recent studies have presented doubts about these findings. The possible association of physical activity, nutrition, and the risk of lung cancer development remains controversial. Further prospective studies should be conducted to determine the potential influence of these 2 risk factors. Copyright © 2013 Elsevier Inc. All rights reserved.

Current Management Strategy for Active Surveillance in Prostate Cancer.

Science.gov (United States)

Syed, Jamil S; Javier-Desloges, Juan; Tatzel, Stephanie; Bhagat, Ansh; Nguyen, Kevin A; Hwang, Kevin; Kim, Sarah; Sprenkle, Preston C

2017-02-01

Active surveillance has been increasingly utilized as a strategy for the management of favorable-risk, localized prostate cancer. In this review, we describe contemporary management strategies of active surveillance, with a focus on traditional stratification schemes, new prognostic tools, and patient outcomes. Patient selection, follow-up strategy, and indication for delayed intervention for active surveillance remain centered around PSA, digital rectal exam, and biopsy findings. Novel tools which include imaging, biomarkers, and genetic assays have been investigated as potential prognostic adjuncts; however, their role in active surveillance remains institutionally dependent. Although 30-50% of patients on active surveillance ultimately undergo delayed treatment, the vast majority will remain free of metastasis with a low risk of dying from prostate cancer. The optimal method for patient selection into active surveillance is unknown; however, cancer-specific mortality rates remain excellent. New prognostication tools are promising, and long-term prospective, randomized data regarding their use in active surveillance will be beneficial.

Kaempferia parviflora Extract Exhibits Anti-cancer Activity against HeLa Cervical Cancer Cells.

Science.gov (United States)

Potikanond, Saranyapin; Sookkhee, Siriwoot; Na Takuathung, Mingkwan; Mungkornasawakul, Pitchaya; Wikan, Nitwara; Smith, Duncan R; Nimlamool, Wutigri

2017-01-01

Kaempferia parviflora (KP) has been traditionally used as a folk remedy to treat several diseases including cancer, and several studies have reported cytotoxic activities of extracts of KP against a number of different cancer cell lines. However, many aspects of the molecular mechanism of action of KP remain unclear. In particular, the ability of KP to regulate cancer cell growth and survival signaling is still largely unexplored. The current study aimed to investigate the effects of KP on cell viability, cell migration, cell invasion, cell apoptosis, and on signaling pathways related to growth and survival of cervical cancer cells, HeLa. We discovered that KP reduced HeLa cell viability in a concentration-dependent manner. The potent cytotoxicity of KP against HeLa cells was associated with a dose-dependent induction of apoptotic cell death as determined by flow cytometry and observation of nuclear fragmentation. Moreover, KP-induced cell apoptosis was likely to be mediated through the intrinsic apoptosis pathway since caspase 9 and caspase 7, but not BID, were shown to be activated after KP exposure. Based on the observation that KP induced apoptosis in HeLa cell, we further investigated the effects of KP at non-cytotoxic concentrations on suppressing signal transduction pathways relevant to cell growth and survival. We found that KP suppressed the MAPK and PI3K/AKT signaling pathways in cells activated with EGF, as observed by a significant decrease in phosphorylation of ERK1/2, Elk1, PI3K, and AKT. The data suggest that KP interferes with the growth and survival of HeLa cells. Consistent with the inhibitory effect on EGF-stimulated signaling, KP potently suppressed the migration of HeLa cells. Concomitantly, KP was demonstrated to markedly inhibit HeLa cell invasion. The ability of KP in suppressing the migration and invasion of HeLa cells was associated with the suppression of matrix metalloproteinase-2 production. These data strongly suggest that KP may slow

The effect of direct referral for fast CT scan in early lung cancer detection in general practice. A clinical, cluster-randomised trial.

Science.gov (United States)

Guldbrandt, Louise Mahncke

2015-03-01

This PhD thesis is based on the project "The effect of direct referral for fast CT scan in early lung cancer detection in general practice. A clinical, cluster-randomised trial", performed in Denmark in 2010-2013. The thesis includes four papers and focuses on early lung cancer diagnostics in general practice. A total of 4200 new cases of lung cancer are diagnosed in Denmark annually. The stage of the disease is an important prognostic factor; thus, the opportunity for curative treatment declines with more advanced tumour stage. Lung cancer patients in Denmark (like in the UK) have a poorer prognosis than lung cancer patients in other European countries. One explanation could be delayed diagnosis. A fast-track pathway was therefore introduced in an attempt to expedite the diagnosis of cancer. However, it seems that not all patients can be diagnosed through this pathway. In order to ensure fast and early lung cancer diagnosis, it is crucial to examine the initial diagnostic process in general and the role general practice plays in lung cancer diagnostics in particular. The specific areas of investigation include the pathways to diagnosis, the characteristics of patients who are at special risk of delayed diagnosis and the level of prediagnostic activity in general practice. A chest radiograph is often the first choice in the investigation of lung cancer. Unfortunately, radiographs are less suitable for central and small tumours. Low-dose computer tomography (LDCT), however, has a high sensitivity for lung cancer which implies that it can be used to detect patients with localised, potentially curable disease. The aim of this thesis was to increase our knowledge of the initial stages of lung cancer diagnostics in general practice. The thesis also examined the effect of a direct referral from general practice to an additional diagnostic test, the LDCT. The aims of this thesis were: 1) To describe Danish patients' pathways to the diagnosis of lung cancer in general and

The effect of breast cancer awareness month on internet search activity - a comparison with awareness campaigns for lung and prostate cancer

LENUS (Irish Health Repository)

Glynn, Ronan W

2011-10-12

Abstract Background This work aimed to assess the effects of the annual breast cancer awareness campaign on internet search activity, and to compare these effects with those of similar campaigns in prostate and lung cancer. We further aimed to assess overall levels of online activity relating to all three neoplasms between 2004 and 2009. Methods Google Insights for Search was employed to examine search trends for the term "breast cancer", across all Google domains between January 2004 and December 2009 (6 years). Search trends for both "prostate cancer" and "lung cancer" across all domains were also analysed for the same period, and these trends were compared with those for "breast cancer". Repeated measures ANOVA and Tukey post-hoc analyses were performed to assess for significant differences in activity. Results Increased levels of online activity relating to breast cancer are consistently generated each October. There is a significantly higher level of background activity in breast cancer compared with that in lung or prostate cancer (p < 0.001), and the October campaign stimulates online activity more effectively than equivalent campaigns for these other malignancies (p < 0.001). Conclusions The annual breast cancer awareness campaign is proving effective in stimulating online activity and may hold useful lessons for other cancer awareness initiatives.

Long non-coding RNA H19 suppresses retinoblastoma progression via counteracting miR-17-92 cluster.

Science.gov (United States)

Zhang, Aihui; Shang, Weiwei; Nie, Qiaoli; Li, Ting; Li, Suhui

2018-04-01

Long non-coding RNAs (lncRNAs) are frequently dysregulated and play important roles in many cancers. lncRNA H19 is one of the earliest discovered lncRNAs which has diverse roles in different cancers. However, the expression, roles, and action mechanisms of H19 in retinoblastoma are still largely unknown. In this study, we found that H19 is downregulated in retinoblastoma tissues and cell lines. Gain-of-function and loss-of-function assays showed that H19 inhibits retinoblastoma cell proliferation, induces retinoblastoma cell cycle arrest and cell apoptosis. Mechanistically, we identified seven miR-17-92 cluster binding sites on H19, and found that H19 directly bound to miR-17-92 cluster via these seven binding sites. Through binding to miR-17-92 cluster, H19 relieves the suppressing roles of miR-17-92 cluster on p21. Furthermore, H19 represses STAT3 activation induced by miR-17-92 cluster. Hence, our results revealed that H19 upregulates p21 expression, inhibits STAT3 phosphorylation, and downregulates the expression of STAT3 target genes BCL2, BCL2L1, and BIRC5. In addition, functional assays demonstrated that the mutation of miR-17-92 cluster binding sites on H19 abolished the proliferation inhibiting, cell cycle arrest and cell apoptosis inducing roles of H19 in retinoblastoma. In conclusion, our data suggested that H19 inhibits retinoblastoma progression via counteracting the roles of miR-17-92 cluster, and implied that enhancing the action of H19 may be a promising therapeutic strategy for retinoblastoma. © 2017 Wiley Periodicals, Inc.

Potential Anti-Cancer Activities and Mechanisms of Costunolide and Dehydrocostuslactone

Directory of Open Access Journals (Sweden)

Xuejing Lin

2015-05-01

Full Text Available Costunolide (CE and dehydrocostuslactone (DE are derived from many species of medicinal plants, such as Saussurea lappa Decne and Laurus nobilis L. They have been reported for their wide spectrum of biological effects, including anti-inflammatory, anticancer, antiviral, antimicrobial, antifungal, antioxidant, antidiabetic, antiulcer, and anthelmintic activities. In recent years, they have caused extensive interest in researchers due to their potential anti-cancer activities for various types of cancer, and their anti-cancer mechanisms, including causing cell cycle arrest, inducing apoptosis and differentiation, promoting the aggregation of microtubule protein, inhibiting the activity of telomerase, inhibiting metastasis and invasion, reversing multidrug resistance, restraining angiogenesis has been studied. This review will summarize anti-cancer activities and associated molecular mechanisms of these two compounds for the purpose of promoting their research and application.

A cross-sectional cluster analysis of the combined association of physical activity and sleep with sociodemographic and health characteristics in mid-aged and older adults.

Science.gov (United States)

Rayward, Anna T; Duncan, Mitch J; Brown, Wendy J; Plotnikoff, Ronald C; Burton, Nicola W

2017-08-01

This study aimed to identify how different patterns of physical activity, sleep duration and sleep quality cluster together, and to examine how the identified clusters differ in terms of socio-demographic and health characteristics. Participants were adults from Brisbane, Australia, aged 42-72 years who reported their physical activity, sleep duration, sleep quality, socio-demographic and health characteristics in 2011 (n=5854). Two-step Cluster Analyses were used to identify clusters. Cluster differences in socio-demographic and health characteristics were examined using chi square tests (phealth characteristics and a high proportion of participants with low physical activity. Physical activity, sleep duration and sleep quality cluster together in distinct patterns and clusters of poor behaviours are associated with poor health status. Multiple health behaviour change interventions which target both physical activity and sleep should be prioritised to improve health outcomes in mid-aged adults. Copyright © 2017 Elsevier B.V. All rights reserved.

The Durban Auto Cluster

DEFF Research Database (Denmark)

Lorentzen, Jochen; Robbins, Glen; Barnes, Justin

2004-01-01

The paper describes the formation of the Durban Auto Cluster in the context of trade liberalization. It argues that the improvement of operational competitiveness of firms in the cluster is prominently due to joint action. It tests this proposition by comparing the gains from cluster activities...

APOBEC3 cytidine deaminases in double-strand DNA break repair and cancer promotion.

Science.gov (United States)

Nowarski, Roni; Kotler, Moshe

2013-06-15

High frequency of cytidine to thymidine conversions was identified in the genome of several types of cancer cells. In breast cancer cells, these mutations are clustered in long DNA regions associated with single-strand DNA (ssDNA), double-strand DNA breaks (DSB), and genomic rearrangements. The observed mutational pattern resembles the deamination signature of cytidine to uridine carried out by members of the APOBEC3 family of cellular deaminases. Consistently, APOBEC3B (A3B) was recently identified as the mutational source in breast cancer cells. A3G is another member of the cytidine deaminases family predominantly expressed in lymphoma cells, where it is involved in mutational DSB repair following ionizing radiation treatments. This activity provides us with a new paradigm for cancer cell survival and tumor promotion and a mechanistic link between ssDNA, DSBs, and clustered mutations. Cancer Res; 73(12); 3494-8. ©2013 AACR. ©2013 AACR.

Contact-based ligand-clustering approach for the identification of active compounds in virtual screening

Directory of Open Access Journals (Sweden)

Mantsyzov AB

2012-09-01

Full Text Available Alexey B Mantsyzov,1 Guillaume Bouvier,2 Nathalie Evrard-Todeschi,1 Gildas Bertho11Université Paris Descartes, Sorbonne, Paris, France; 2Institut Pasteur, Paris, FranceAbstract: Evaluation of docking results is one of the most important problems for virtual screening and in silico drug design. Modern approaches for the identification of active compounds in a large data set of docked molecules use energy scoring functions. One of the general and most significant limitations of these methods relates to inaccurate binding energy estimation, which results in false scoring of docked compounds. Automatic analysis of poses using self-organizing maps (AuPosSOM represents an alternative approach for the evaluation of docking results based on the clustering of compounds by the similarity of their contacts with the receptor. A scoring function was developed for the identification of the active compounds in the AuPosSOM clustered dataset. In addition, the AuPosSOM efficiency for the clustering of compounds and the identification of key contacts considered as important for its activity, were also improved. Benchmark tests for several targets revealed that together with the developed scoring function, AuPosSOM represents a good alternative to the energy-based scoring functions for the evaluation of docking results.Keywords: scoring, docking, virtual screening, CAR, AuPosSOM

Emission line galaxies and active galactic nuclei in WINGS clusters

Science.gov (United States)

Marziani, P.; D'Onofrio, M.; Bettoni, D.; Poggianti, B. M.; Moretti, A.; Fasano, G.; Fritz, J.; Cava, A.; Varela, J.; Omizzolo, A.

2017-03-01

We present the analysis of the emission line galaxies members of 46 low-redshift (0.04 employing diagnostic diagrams. We examined the emission line properties and frequencies of star-forming galaxies, transition objects, and active galactic nuclei (AGNs: LINERs and Seyferts), unclassified galaxies with emission lines, and quiescent galaxies with no detectable line emission. A deficit of emission line galaxies in the cluster environment is indicated by both a lower frequency, and a systematically lower Balmer emission line equivalent width and luminosity with respect to control samples; this implies a lower amount of ionized gas per unit mass and a lower star formation rate if the source is classified as Hii region. A sizable population of transition objects and of low-luminosity LINERs (≈ 10-20% of all emission line galaxies) are detected among WINGS cluster galaxies. These sources are a factor of ≈1.5 more frequent, or at least as frequent, as in control samples with respect to Hii sources. Transition objects and LINERs in clusters are most affected in terms ofline equivalent width by the environment and appear predominantly consistent with so-called retired galaxies. Shock heating can be a possible gas excitation mechanism that is able to account for observed line ratios. Specific to the cluster environment, we suggest interaction between atomic and molecular gas and the intracluster medium as a possible physical cause of line-emitting shocks. The data whose description is provided in Table B.1, and emission line catalog of the WINGS database are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/599/A83

Tumor-suppressor activity of RRIG1 in breast cancer

International Nuclear Information System (INIS)

Zhang, Guihong; Brewster, Abenaa; Guan, Baoxiang; Fan, Zhen; Brown, Powel H; Xu, Xiao-Chun

2011-01-01

Retinoid receptor-induced gene-1 (RRIG1) is a novel gene that has been lost in several types of human cancers. The aim of this study was to determine whether RRIG1 plays a role in breast cancer, such as in the suppression of breast cancer cell growth and invasion. Immunohistochemistry was used to detect RRIG1 expression in breast tissue specimens. Gene transfection was used to restore or knock down RRIG1 expression in breast cancer cell lines for analysis of cell viability, colony formation, and migration/invasion potential. Reverse-transcription polymerase chain reaction and western blot assays were used to detect the changes in gene expression. The RhoA activation assay was used to assess RRIG1-induced inhibition of RhoA activity. The immunohistochemical data showed that RRIG1 expression was reduced in breast cancer tissues compared with normal and atypical hyperplastic breast tissues. RRIG1 expression was inversely correlated with lymph node metastasis of breast cancer but was not associated with the status of hormone receptors, such as estrogen receptor, progesterone receptor, or HER2. Furthermore, restoration of RRIG1 expression inhibited proliferation, colony formation, migration, and invasion of breast cancer cells. Expression of RRIG1 also reduced phosphorylated Erk1/2 and Akt levels; c-Jun, MMP9, and Akt expressions; and RhoA activity. In contrast, knockdown of RRIG1 expression promoted breast cancer cell proliferation, colony formation, migration, and invasion potential. The data from the current study indicated that RRIG1 expression was reduced or lost in breast cancer and that restoration of RRIG1 expression suppressed breast cancer cell growth and invasion capacity. Future studies will determine the underlying molecular mechanisms and define RRIG1 as a tumor-suppressor gene in breast cancer

Physical activity and survival in breast cancer

DEFF Research Database (Denmark)

Ammitzbøll, Gunn; Søgaard, Karen; Karlsen, Randi V

2016-01-01

PURPOSE: Knowledge about lifestyle factors possibly influencing survival after breast cancer (BC) is paramount. We examined associations between two types of postdiagnosis physical activity (PA) and overall survival after BC. PATIENTS AND METHODS: We used prospective data on 959 BC survivors from...... the Diet, Cancer, and Health cohort, all enrolled before diagnosis. Self-reported PA was measured as time per activity, and estimated metabolic equivalent task (MET)-hours per week were summed for each activity. We constructed measures for household, exercise, and total PA. The association between...... from all causes during the study period. In adjusted analyses, exercise PA above eight MET h/week compared to lower levels of activity was significantly associated with improved overall survival (HR, 0.68; confidence interval [CI]: 0.47-0.99). When comparing participation in exercise to non...

The clustering of diet, physical activity and sedentary behavior in children and adolescents: a review

Science.gov (United States)

2014-01-01

Diet, physical activity (PA) and sedentary behavior are important, yet modifiable, determinants of obesity. Recent research into the clustering of these behaviors suggests that children and adolescents have multiple obesogenic risk factors. This paper reviews studies using empirical, data-driven methodologies, such as cluster analysis (CA) and latent class analysis (LCA), to identify clustering patterns of diet, PA and sedentary behavior among children or adolescents and their associations with socio-demographic indicators, and overweight and obesity. A literature search of electronic databases was undertaken to identify studies which have used data-driven methodologies to investigate the clustering of diet, PA and sedentary behavior among children and adolescents aged 5–18 years old. Eighteen studies (62% of potential studies) were identified that met the inclusion criteria, of which eight examined the clustering of PA and sedentary behavior and eight examined diet, PA and sedentary behavior. Studies were mostly cross-sectional and conducted in older children and adolescents (≥9 years). Findings from the review suggest that obesogenic cluster patterns are complex with a mixed PA/sedentary behavior cluster observed most frequently, but healthy and unhealthy patterning of all three behaviors was also reported. Cluster membership was found to differ according to age, gender and socio-economic status (SES). The tendency for older children/adolescents, particularly females, to comprise clusters defined by low PA was the most robust finding. Findings to support an association between obesogenic cluster patterns and overweight and obesity were inconclusive, with longitudinal research in this area limited. Diet, PA and sedentary behavior cluster together in complex ways that are not well understood. Further research, particularly in younger children, is needed to understand how cluster membership differs according to socio-demographic profile. Longitudinal research

Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival

Directory of Open Access Journals (Sweden)

Hsieh Fu-Chuan

2008-10-01

Full Text Available Abstract Background Constitutive activation of signal transducer and activator of transcription 3 (Stat3 signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer. Results We found that elevated Stat3 phosphorylation in 19 of 100 (19% bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC. The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin and a cell cycle regulating gene (cyclin D1 was associated with the cell growth inhibition and apoptosis. Conclusion These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.

Cancer-related fatigue and physical activity among premenopausal cervical and endometrial cancer survivors in Japan.

Science.gov (United States)

Obama, Kyoko; Maru, Mitsue; Maeda, Rumi; Kubota, Toshiro

2015-09-30

To examine the relationship between cancer-related fatigue (CRF) and physical activity in daily living in premenopausal disease-free cervical and endometrial cancer survivors. A physical activity monitor was used to collect objective data on daily physical activity. CRF and related variables were measured using self-report scales in a cross-sectional manner. The average age was 44.9 years among 64 women. The higher CRF group comprised 22 women (34%), 10% of whom had severe fatigue. The participants had higher physical activity levels compared with the findings in previous studies, and reported an average of 40 min/day of moderate to vigorous activity. Moderate to vigorous levels of physical activity were derived from essential social activities rather than leisure time exercise. There were no significant differences in physical activity levels between the lower and higher CRF groups. Our study results suggested that the higher level of physical activity in daily living itself had no relationship with decreasing CRF among premenopausal cervical and endometrial cancer survivors. It would be better to focus on cognitive and psychological factors before introducing physical activity programs and be careful of the characteristics of the participants' physical activity among this population in daily basis.

ACTIVE GALACTIC NUCLEUS FEEDBACK AND ENTROPY INJECTION IN GALAXY CLUSTER CORES

International Nuclear Information System (INIS)

Chaudhuri, Anya; Majumdar, Subhabrata; Nath, Biman B.

2013-01-01

We make the first estimate of non-gravitational energy profiles in galaxy cluster cores (and beyond) based on observational data. Comparing the observed entropy profiles within r 500 , from the Representative XMM-Newton Cluster Structure Survey to simulated base entropy profiles without feedback from both adaptive mesh refinement (AMR) and smoothed particle hydrodynamic (SPH) non-radiative simulations, we estimate the amount of additional non-gravitational energy, E ICM , contained in the intracluster medium (ICM), as well as the total energy feedback, E Feedback , from active galactic nuclei (AGNs; the central AGNs in most cases) into the clusters. The total feedback energy scales with the mean spectroscopic temperature as E Feedback ∝T sp 2.52±0.08 and E Feedback ∝T sp 2.17±0.11 for the SPH and AMR baseline profiles. The mean non-gravitational energy per particle within r 500 remaining in the ICM after energy lost during cooling is ε ICM = 2.8 ± 0.8 keV for the SPH theoretical relation and ε ICM = 1.7 ± 0.9 keV for the AMR theoretical relation. We use the NRAO/VLA Sky Survey source catalog to determine the radio luminosity, L R , at 1.4 GHz of the central source(s) of our sample. For T sp > 3 keV, the E Feedback correlates with L R , although with different normalization for cool-core and non-cool-core clusters. We show that AGNs could provide a significant portion of the feedback

Neighborhood influences on recreational physical activity and survival after breast cancer.

Science.gov (United States)

Keegan, Theresa H M; Shariff-Marco, Salma; Sangaramoorthy, Meera; Koo, Jocelyn; Hertz, Andrew; Schupp, Clayton W; Yang, Juan; John, Esther M; Gomez, Scarlett L

2014-10-01

Higher levels of physical activity have been associated with improved survival after breast cancer diagnosis. However, no previous studies have considered the influence of the social and built environment on physical activity and survival among breast cancer patients. Our study included 4,345 women diagnosed with breast cancer (1995-2008) from two population-based studies conducted in the San Francisco Bay Area. We examined questionnaire-based moderate/strenuous recreational physical activity during the 3 years before diagnosis. Neighborhood characteristics were based on data from the 2000 US Census, business listings, parks, farmers' markets, and Department of Transportation. Survival was evaluated using multivariable Cox proportional hazards models, with follow-up through 2009. Women residing in neighborhoods with no fast-food restaurants (vs. fewer fast-food restaurants) to other restaurants, high traffic density, and a high percentage of foreign-born residents were less likely to meet physical activity recommendations set by the American Cancer Society. Women who were not recreationally physically active had a 22% higher risk of death from any cause than women that were the most active. Poorer overall survival was associated with lower neighborhood socioeconomic status (SES) (p(trend) = 0.02), whereas better breast cancer-specific survival was associated with a lack of parks, especially among women in high-SES neighborhoods. Certain aspects of the neighborhood have independent associations with recreational physical activity among breast cancer patients and their survival. Considering neighborhood factors may aide in the design of more effective, tailored physical activity programs for breast cancer survivors.

Single to Two Cluster State Transition of Primary Motor Cortex 4-posterior (MI-4p Activities in Humans

Directory of Open Access Journals (Sweden)

Kazunori Nakada

2015-11-01

Full Text Available The human primary motor cortex has dual representation of the digits, namely, area 4 anterior (MI-4a and area 4 posterior (MI-4p. We have previously demonstrated that activation of these two functional subunits can be identified independently by functional magnetic resonance imaging (fMRI using independent component-cross correlation-sequential epoch (ICS analysis. Subsequent studies in patients with hemiparesis due to subcortical lesions and monoparesis due to peripheral nerve injury demonstrated that MI-4p represents the initiation area of activation, whereas MI-4a is the secondarily activated motor cortex requiring a “long-loop” feedback input from secondary motor systems, likely the cerebellum. A dynamic model of hand motion based on the limit cycle oscillator predicts that the specific pattern of entrainment of neural firing may occur by applying appropriate periodic stimuli. Under normal conditions, such entrainment introduces a single phase-cluster. Under pathological conditions where entrainment stimuli have insufficient strength, the phase cluster splits into two clusters. Observable physiological phenomena of this shift from single cluster to two clusters are: doubling of firing rate of output neurons; or decay in group firing density of the system due to dampening of odd harmonics components. While the former is not testable in humans, the latter can be tested by appropriately designed fMRI experiments, the quantitative index of which is believed to reflect group behavior of neurons functionally localized, e.g., firing density in the dynamic theory. Accordingly, we performed dynamic analysis of MI-4p activation in normal volunteers and paretic patients. The results clearly indicated that MI-4p exhibits a transition from a single to a two phase-cluster state which coincided with loss of MI-4a activation. The study demonstrated that motor dysfunction (hemiparesis in patients with a subcortical infarct is not simply due to afferent

Spots and the Activity of Stars in the Hyades Cluster from Observations with the Kepler Space Telescope (K2)

Science.gov (United States)

Savanov, I. S.; Dmitrienko, E. S.

2018-03-01

Observations of the K2 mission (continuing the program of the Kepler Space Telescope) are used to estimate the spot coverage S (the fractional area of spots on the surface of an active star) for stars of the Hyades cluster. The analysis is based on data on the photometric variations of 47 confirmed single cluster members, together with their atmospheric parameters, masses, and rotation periods. The resulting values of S for these Hyades objects are lower than those stars of the Pleiades cluster (on average, by Δ S 0.05-0.06). A comparison of the results of studies of cool, low-mass dwarfs in the Hyades and Pleiades clusters, as well as the results of a study of 1570 M stars from the main field observed in the Kepler SpaceMission, indicates that the Hyades stars are more evolved than the Pleiades stars, and demonstrate lower activity. The activity of seven solar-type Hyades stars ( S = 0.013 ± 0.006) almost approaches the activity level of the present-day Sun, and is lower than the activity of solar-mass stars in the Pleiades ( S = 0.031 ± 0.003). Solar-type stars in the Hyades rotate faster than the Sun ( = 8.6 d ), but slower than similar Pleiades stars.

The role of outsourcing in the mechanism of economic security activities of cluster formations

Directory of Open Access Journals (Sweden)

T. I. Ovchinnikova

2016-01-01

Full Text Available The article considers the concept of “outsourcing”, “economic safety’, “cluster formation”. Outsourcing is defined as external influences that contribute to the effective operation of the enterprise. The economic essence of "outsourcing" in the research and domestic practice, which has hitherto manifested itself only as a method of attracting temporary workers in the field. On the example of the dairy industry is studied safe operation as sustainable, and competitive Bozrikova their behavior with regard to outsourcing. Studied the differences of the processes of cooperation, subcontracting and clustering. Stated that cooperation and subcontracting are the component parts outsourcing, which covers the process of production or provision of services; the outsourcing justifies: the transfer of technical functions or business processes, and thus part of the risks transferred to the outsourcing provider. An example of adaptive modeling outsourcing, suggesting that in the future, the projected volume of production, processing and sales of dairy products manufactured by the enterprises of dairy industry of the Voronezh region belonging to a cluster will be reduced through the introduction of a mechanism of outsourcing. It proves that the risk of bankruptcy of enterprises on the basis of adaptive models. The application of the mechanism of outsourcing in order to increase the economic security, in particular, such of its functions as the transmission of external organizations not only certain social functions (such as the use of temporary workers, but also the activities of the business processes to optimize all kinds of resources and concentration of efforts on the core activities of each company within the cluster APK. Analysis conducted by the authors suggests: in the future, the projected volume of production, processing and sales of dairy products manufactured by the enterprises of agriculture, dairy production and trade of the Voronezh

Toward the identification of communities with increased tobacco-associated cancer burden: Application of spatial modeling techniques

Directory of Open Access Journals (Sweden)

Noella A Dietz

2011-01-01

Full Text Available Introduction: Smoking-attributable risks for lung, esophageal, and head and neck (H/N cancers range from 54% to 90%. Identifying areas with higher than average cancer risk and smoking rates, then targeting those areas for intervention, is one approach to more rapidly lower the overall tobacco disease burden in a given state. Our research team used spatial modeling techniques to identify areas in Florida with higher than expected tobacco-associated cancer incidence clusters. Materials and Methods: Geocoded tobacco-associated incident cancer data from 1998 to 2002 from the Florida Cancer Data System were used. Tobacco-associated cancers included lung, esophageal, and H/N cancers. SaTScan was used to identify geographic areas that had statistically significant (P<0.10 excess age-adjusted rates of tobacco-associated cancers. The Poisson-based spatial scan statistic was used. Phi correlation coefficients were computed to examine associations among block groups with/without overlapping cancer clusters. The logistic regression was used to assess associations between county-level smoking prevalence rates and being diagnosed within versus outside a cancer cluster. Community-level smoking rates were obtained from the 2002 Florida Behavioral Risk Factor Surveillance System (BRFSS. Analyses were repeated using 2007 BRFSS to examine the consistency of associations. Results: Lung cancer clusters were geographically larger for both squamous cell and adenocarcinoma cases in Florida from 1998 to 2002, than esophageal or H/N clusters. There were very few squamous cell and adenocarcinoma esophageal cancer clusters. H/N cancer mapping showed some squamous cell and a very small amount of adenocarcinoma cancer clusters. Phi correlations were generally weak to moderate in strength. The odds of having an invasive lung cancer cluster increased by 12% per increase in the county-level smoking rate. Results were inconsistent for esophageal and H/N cancers, with some

ING3 promotes prostate cancer growth by activating the androgen receptor.

Science.gov (United States)

Nabbi, Arash; McClurg, Urszula L; Thalappilly, Subhash; Almami, Amal; Mobahat, Mahsa; Bismar, Tarek A; Binda, Olivier; Riabowol, Karl T

2017-05-16

The androgen receptor (AR) is a major driver of prostate cancer, and increased AR levels and co-activators of the receptor promote the development of prostate cancer. INhibitor of Growth (ING) proteins target lysine acetyltransferase or lysine deacetylase complexes to the histone H3K4Me3 mark of active transcription, to affect chromatin structure and gene expression. ING3 is a stoichiometric member of the TIP60 lysine acetyltransferase complex implicated in prostate cancer development. Biopsies of 265 patients with prostate cancer were stained for ING3, pan-cytokeratin, and DNA. LNCaP and C4-2 androgen-responsive cells were used for in vitro assays including immunoprecipitation, western blotting, Luciferase reporter assay and quantitative polymerase chain reaction. Cell viability and migration assays were performed in prostate cancer cell lines using scrambled siRNA or siRNA targeting ING3. We find that ING3 levels and AR activity positively correlate in prostate cancer. ING3 potentiates androgen effects, increasing expression of androgen-regulated genes and androgen response element-driven reporters to promote growth and anchorage-independent growth. Conversely, ING3 knockdown inhibits prostate cancer cell growth and invasion. ING3 activates the AR by serving as a scaffold to increase interaction between TIP60 and the AR in the cytoplasm, enhancing receptor acetylation and translocation to the nucleus. Activation is independent of ING3's ability to target the TIP60 complex to H3K4Me3, identifying a previously unknown chromatin-independent cytoplasmic activity for ING3. In agreement with in vitro observations, analysis of The Cancer Genome Atlas (TCGA) data (n = 498) and a prostate cancer tissue microarray (n = 256) show that ING3 levels are higher in aggressive prostate cancers, with high levels of ING3 predicting shorter patient survival in a low AR subgroup. Including ING3 levels with currently used indicators such as the Gleason score provides more

Clustering of near clusters versus cluster compactness

International Nuclear Information System (INIS)

Yu Gao; Yipeng Jing

1989-01-01

The clustering properties of near Zwicky clusters are studied by using the two-point angular correlation function. The angular correlation functions for compact and medium compact clusters, for open clusters, and for all near Zwicky clusters are estimated. The results show much stronger clustering for compact and medium compact clusters than for open clusters, and that open clusters have nearly the same clustering strength as galaxies. A detailed study of the compactness-dependence of correlation function strength is worth investigating. (author)

A Facile Synthesis of Graphene-WO3 Nanowire Clusters with High Photocatalytic Activity for O2 Evolution

Directory of Open Access Journals (Sweden)

M.-J. Zhou

2014-01-01

Full Text Available In the present work, graphene-WO3 nanowire clusters were synthesized via a facile hydrothermal method. The obtained graphene-WO3 nanowire clusters were characterized by X-ray diffraction (XRD, transmission electron microscopy (TEM, X-ray photoelectron spectroscopy (XPS, Fourier transform infrared spectroscopy (FT-IR, Raman spectroscopy, and ultraviolet-visible diffuse reflectance spectroscopy (DRS techniques. The photocatalytic oxygen (O2 evolution properties of the as-synthesized samples were investigated by measuring the amount of evolved O2 from water splitting. The graphene-WO3 nanowire clusters exhibited enhanced performance compared to pure WO3 nanowire clusters for O2 evolution. The amount of evolved O2 from water splitting after 8 h for the graphene-WO3 nanowire clusters is ca. 0.345 mmol/L, which is more than 1.9 times as much as that of the pure WO3 nanowire clusters (ca. 0.175 mmol/L. The high photocatalytic activity of the graphene-WO3 nanowire clusters was attributed to a high charge transfer rate in the presence of graphene.

Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer

International Nuclear Information System (INIS)

Kim, Tae-Dong; Song, Kyoung-Sub; Li, Ge; Choi, Hoon; Park, Hae-Duck; Lim, Kyu; Hwang, Byung-Doo; Yoon, Wan-Hee

2006-01-01

Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (uPA) are involved in colorectal cancer invasion and metastasis. There is still debate whether the activity of MMP-2 and MMP-9 differs between tumors located in the colon and rectum. We designed this study to determine any differences in the expression of MMP-2, MMP-9 and uPA system between colon and rectal cancer tissues. Cancer tissue samples were obtained from colon carcinoma (n = 12) and rectal carcinomas (n = 10). MMP-2 and MMP-9 levels were examined using gelatin zymography and Western blotting; their endogenous inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), were assessed by Western blotting. uPA, uPAR and PAI-1 were examined using enzyme-linked immunosorbent assay (ELISA). The activity of uPA was assessed by casein-plasminogen zymography. In both colon and rectal tumors, MMP-2, MMP-9 and TIMP-1 protein levels were higher than in corresponding paired normal mucosa, while TIMP-2 level in tumors was significantly lower than in normal mucosa. The enzyme activities or protein levels of MMP-2, MMP-9 and their endogenous inhibitors did not reach a statistically significant difference between colon and rectal cancer compared with their normal mucosa. In rectal tumors, there was an increased activity of uPA compared with the activity in colon tumors (P = 0.0266), however urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) showed no significant difference between colon and rectal cancer tissues. These findings suggest that uPA may be expressed differentially in colon and rectal cancers, however, the activities or protein levels of MMP-2, MMP-9, TIMP-1, TIMP-2, PAI-1 and uPAR are not affected by tumor location in the colon or the rectum

Global methylation silencing of clustered proto-cadherin genes in cervical cancer: serving as diagnostic markers comparable to HPV

International Nuclear Information System (INIS)

Wang, Kai-Hung; Lin, Cuei-Jyuan; Liu, Chou-Jen; Liu, Dai-Wei; Huang, Rui-Lan; Ding, Dah-Ching; Weng, Ching-Feng; Chu, Tang-Yuan

2015-01-01

Epigenetic remodeling of cell adhesion genes is a common phenomenon in cancer invasion. This study aims to investigate global methylation of cell adhesion genes in cervical carcinogenesis and to apply them in early detection of cancer from cervical scraping. Genome-wide methylation array was performed on an investigation cohort, including 16 cervical intraepithelial neoplasia 3 (CIN3) and 20 cervical cancers (CA) versus 12 each of normal, inflammation and CIN1 as controls. Twelve members of clustered proto-cadherin (PCDH) genes were collectively methylated and silenced, which were validated in cancer cells of the cervix, endometrium, liver, head and neck, breast, and lung. In an independent cohort including 107 controls, 66 CIN1, 85 CIN2/3, and 38 CA, methylated PCDHA4 and PCDHA13 were detected in 2.8%, 24.2%, 52.9%, and 84.2% (P < 10 −25 ), and 2.8%, 24.2%, 50.6%, and 94.7% (P < 10 −29 ), respectively. In diagnosis of CIN2 or more severe lesion of the cervix, a combination test of methylated PCDHA4 or PCDHA13 from cervical scraping had a sensitivity, specificity, positive predictive value, and negative predictive value of 74.8%, 80.3%, 73%, and 81.8%, respectively. Testing of this combination from cervical scraping is equally sensitive but more specific than human papillomavirus (HPV) test in diagnosis of CIN2 or more severe lesions. The study disclosed a collective methylation of PCDH genes in cancer of cervix and other sites. At least two of them can be promising diagnostic markers for cervical cancer noninferior to HPV

Clustering of resting state networks.

Directory of Open Access Journals (Sweden)

Megan H Lee

Full Text Available The goal of the study was to demonstrate a hierarchical structure of resting state activity in the healthy brain using a data-driven clustering algorithm.The fuzzy-c-means clustering algorithm was applied to resting state fMRI data in cortical and subcortical gray matter from two groups acquired separately, one of 17 healthy individuals and the second of 21 healthy individuals. Different numbers of clusters and different starting conditions were used. A cluster dispersion measure determined the optimal numbers of clusters. An inner product metric provided a measure of similarity between different clusters. The two cluster result found the task-negative and task-positive systems. The cluster dispersion measure was minimized with seven and eleven clusters. Each of the clusters in the seven and eleven cluster result was associated with either the task-negative or task-positive system. Applying the algorithm to find seven clusters recovered previously described resting state networks, including the default mode network, frontoparietal control network, ventral and dorsal attention networks, somatomotor, visual, and language networks. The language and ventral attention networks had significant subcortical involvement. This parcellation was consistently found in a large majority of algorithm runs under different conditions and was robust to different methods of initialization.The clustering of resting state activity using different optimal numbers of clusters identified resting state networks comparable to previously obtained results. This work reinforces the observation that resting state networks are hierarchically organized.

Cancer-related fatigue and physical activity among premenopausal cervical and endometrial cancer survivors in Japan

OpenAIRE

小濵, 京子; 丸, 光惠; 前田, 留美; 久保田, 俊郎

2015-01-01

Purpose: To examine the relationship between cancer-related fatigue (CRF) and physical activity in daily living in premenopausal disease-free cervical and endometrial cancer survivors. Methods: A physical activity monitor was used to collect objective data on daily physical activity. CRF and related variables were measured using self-report scales in a cross-sectional manner. Results: The average age was 44.9 years among 64 women. The higher CRF group comprised 22 women (34%), 10% of whom had...

Spatial analyses identify the geographic source of patients at a National Cancer Institute Comprehensive Cancer Center.

Science.gov (United States)

Su, Shu-Chih; Kanarek, Norma; Fox, Michael G; Guseynova, Alla; Crow, Shirley; Piantadosi, Steven

2010-02-01

We examined the geographic distribution of patients to better understand the service area of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, a designated National Cancer Institute (NCI) comprehensive cancer center located in an urban center. Like most NCI cancer centers, the Sidney Kimmel Comprehensive Cancer Center serves a population beyond city limits. Urban cancer centers are expected to serve their immediate neighborhoods and to address disparities in access to specialty care. Our purpose was to learn the extent and nature of the cancer center service area. Statistical clustering of patient residence in the continental United States was assessed for all patients and by gender, cancer site, and race using SaTScan. Primary clusters detected for all cases and demographically and tumor-defined subpopulations were centered at Baltimore City and consisted of adjacent counties in Delaware, Pennsylvania, Virginia, West Virginia, New Jersey and New York, and the District of Columbia. Primary clusters varied in size by race, gender, and cancer site. Spatial analysis can provide insights into the populations served by urban cancer centers, assess centers' performance relative to their communities, and aid in developing a cancer center business plan that recognizes strengths, regional utility, and referral patterns. Today, 62 NCI cancer centers serve a quarter of the U.S. population in their immediate communities. From the Baltimore experience, we might project that the population served by these centers is actually more extensive and varies by patient characteristics, cancer site, and probably cancer center services offered.

Rationale for promoting physical activity among cancer survivors: literature review and epidemiologic examination.

Science.gov (United States)

Loprinzi, Paul D; Lee, Hyo

2014-03-01

To review the extant literature on the link between physical activity and health outcomes among cancer survivors; identify evidence-based strategies to promote physical activity among this population; and conduct an epidemiologic study based on gaps from the literature review, examining the association between physical activity and various biologic markers. The authors used PubMed and Google Scholar up to July 2013, as well as data from the 2003-2006 National Health and Nutrition Examination Survey for the empirical study. Studies were examined through a systematic review process. In the epidemiologic study, 227 adult cancer survivors wore an accelerometer for four days or longer, with biologic markers (e.g., cholesterol) assessed from a blood sample. The review study demonstrated that cancer survivors are relatively inactive, but physical activity may help to reduce the risk of cancer recurrence and cancer-related mortality, increase cancer treatment rates, reduce pain and other side effects associated with cancer treatment, and improve physical and mental health. The epidemiologic study showed that physical activity was associated with several understudied biomarkers (e.g., neutrophils, white blood cells) that are linked with cancer recurrence, cancer-related mortality, and other chronic diseases. Nurses are encouraged to promote physical activity in cancer survivors.

Computational evaluation of sub-nanometer cluster activity of singly exposed copper atom with various coordinative environment in catalytic CO2 transformation

Science.gov (United States)

Shanmugam, Ramasamy; Thamaraichelvan, Arunachalam; Ganesan, Tharumeya Kuppusamy; Viswanathan, Balasubramanian

2017-02-01

Metal cluster, at sub-nanometer level has a unique property in the activation of small molecules, in contrast to that of bulk surface. In the present work, singly exposed active site of copper metal cluster at sub-nanometer level was designed to arrive at the energy minimised configurations, binding energy, electrostatic potential map, frontier molecular orbitals and partial density of states. The ab initio molecular dynamics was carried out to probe the catalytic nature of the cluster. Further, the stability of the metal cluster and its catalytic activity in the electrochemical reduction of CO2 to CO were evaluated by means of computational hydrogen electrode via calculation of the free energy profile using DFT/B3LYP level of theory in vacuum. The activity of the cluster is ascertained from the fact that the copper atom, present in a two coordinative environment, performs a more selective conversion of CO2 to CO at an applied potential of -0.35 V which is comparatively lower than that of higher coordinative sites. The present study helps to design any sub-nano level metal catalyst for electrochemical reduction of CO2 to various value added chemicals.

A cluster-analytical approach towards physical activity and eating habits among 10-year-old children.

Science.gov (United States)

Sabbe, Dieter; De Bourdeaudhuij, I; Legiest, E; Maes, L

2008-10-01

The purpose was to investigate whether clusters-based on physical activity (PA) and eating habits-can be found among children, and to explore subgroups' characteristics. A total of 1725 10-year olds completed a self-administered questionnaire. K-means cluster analysis was based on the weekly quantity of vigorous and moderate PA, the excess index (weekly consumption of sugar and/or fat) and the daily diversity index. Chi-squares tested gender differences in clusters and associations with socio-economic status (SES), overweight, controlling for gender. Following distribution was reliable: Sporty Healthy Eaters (n=242; high vigorous PA, average moderate PA, low excess, higher diversity), Sporty Mixed Eaters (n=288; high overall PA, very high excess, high diversity), Moderate Active Healthy Eaters (n=221; average vigorous PA, highest moderate PA, lower excess, higher diversity), Unsporting Unhealthy Eaters (n=276; below average on all indexes, diversity extremely low) and Sedentary Healthy Eaters (n=318; lowest overall PA, higher excess, highest diversity). The Sporty Healthy Eaters and Sporty Mixed Eaters comprised more males, Sedentary Healthy Eaters more females. No associations with SES or overweight were found for the clusters. Co-occurrence of healthy and unhealthy behaviour exists. Only Sporty Healthy Eaters combine high levels of PA with low excess index and higher dietary diversity index. Effective ways of directing children to selective, individual relevant recommendations should be developed.

Cluster-cluster clustering

International Nuclear Information System (INIS)

Barnes, J.; Dekel, A.; Efstathiou, G.; Frenk, C.S.; Yale Univ., New Haven, CT; California Univ., Santa Barbara; Cambridge Univ., England; Sussex Univ., Brighton, England)

1985-01-01

The cluster correlation function xi sub c(r) is compared with the particle correlation function, xi(r) in cosmological N-body simulations with a wide range of initial conditions. The experiments include scale-free initial conditions, pancake models with a coherence length in the initial density field, and hybrid models. Three N-body techniques and two cluster-finding algorithms are used. In scale-free models with white noise initial conditions, xi sub c and xi are essentially identical. In scale-free models with more power on large scales, it is found that the amplitude of xi sub c increases with cluster richness; in this case the clusters give a biased estimate of the particle correlations. In the pancake and hybrid models (with n = 0 or 1), xi sub c is steeper than xi, but the cluster correlation length exceeds that of the points by less than a factor of 2, independent of cluster richness. Thus the high amplitude of xi sub c found in studies of rich clusters of galaxies is inconsistent with white noise and pancake models and may indicate a primordial fluctuation spectrum with substantial power on large scales. 30 references

Active home-based cancer treatment

Directory of Open Access Journals (Sweden)

Bordonaro S

2012-06-01

Full Text Available Sebastiano Bordonaro Fabio Raiti, Annamaria Di Mari, Calogera Lopiano, Fabrizio Romano, Vitalinda Pumo, Sebastiano Rametta Giuliano, Margherita Iacono, Eleonora Lanteri, Elena Puzzo, Sebastiano Spada, Paolo TralongoUOC Medical Oncology, RAO, ASP 8 Siracusa, ItalyBackground: Active home-based treatment represents a new model of health care. Chronic treatment requires continuous access to facilities that provide cancer care, with considerable effort, particularly economic, on the part of patients and caregivers. Oral chemotherapy could be limited as a consequence of poor compliance and adherence, especially by elderly patients.Methods: We selected 30 cancer patients referred to our department and treated with oral therapy (capecitabine, vinorelbine, imatinib, sunitinib, sorafenib, temozolomide, ibandronate. This pilot study of oral therapy in the patient’s home was undertaken by a doctor and two nurses with experience in clinical oncology. The instruments used were clinical diaries recording home visits, hospital visits, need for caregiver support, and a questionnaire specially developed by the European Organization for Research and Treatment of Cancer (EORTC, known as the QLQ-C30 version 2.0, concerning the acceptability of oral treatment from the patient’s perspective.Results: This program decreased the need to access cancer facilities by 98.1%, promoted better quality of life for patients, as reflected in increased EORTC QLQ-C30 scores over time, allowing for greater adherence to oral treatment as a result of control of drug administration outside the hospital. This model has allowed treatment of patients with difficult access to care (elderly, disabled or otherwise needed caregivers that in the project represent the majority (78% of these.Conclusions: This model of active home care improves quality of life and adherence with oral therapy, reduces the need to visit the hospital, and consequently decreases the number of lost hours of work on

Effect of surface Fe2O3 clusters on the photocatalytic activity of TiO2 for phenol degradation in water

International Nuclear Information System (INIS)

Sun, Qiong; Leng, Wenhua; Li, Zhen; Xu, Yiming

2012-01-01

Graphical abstract: Surface modified TiO 2 with iron oxide clusters through adsorption and decomposition of a large Fe(III) complex shows an enhanced activity for phenol degradation in water under UV light. But it was only observed with the clusters in a small size and at very low coverage on anatase. Highlights: ► Iron oxide clusters are made by decomposition of a large Fe(III) complex on TiO 2 . ► The modified anatase shows an enhanced activity for phenol photodegradation. ► The composite catalyst is very stable during four repeated experiments. - Abstract: Surface modification of TiO 2 with Fe 2 O 3 clusters was made through chemisorption of ferric phthalocyaninetetracarboxylate onto TiO 2 , followed by sintering in air to remove organic moiety. Solid characterization with electron paramagnetic resonance spectroscopy and other techniques showed that ferric oxides were highly dispersed on TiO 2 as a noncrystallized cluster, while TiO 2 phases remained unchanged. For phenol degradation in aerated aqueous suspension, only the sample containing less than 0.3 at.% Fe was more active than bare TiO 2 under UV light, whereas no activity was found under visible light. As anatase thermally transferred into rutile, the Fe-containing catalyst became less active than bare TiO 2 , mainly ascribed to the increased size of Fe 2 O 3 clusters. In the presence of H 2 O 2 , all Fe-containing catalysts were more active than bare TiO 2 . Moreover, similar trend in activity among different catalysts was also observed with the formation of hydroxyl radicals, and with the generation of photocurrent measured under N 2 with Fe/TiO 2 electrode. Present work clearly shows that only Fe 2 O 3 clusters in a small size and at low coverage on TiO 2 are beneficial to the photocatalytic reaction, while excess iron oxide is detrimental. Possible mechanism is discussed in the text.

Combinations of elevated tissue miRNA-17-92 cluster expression and serum prostate-specific antigen as potential diagnostic biomarkers for prostate cancer.

Science.gov (United States)

Feng, Sujuan; Qian, Xiaosong; Li, Han; Zhang, Xiaodong

2017-12-01

The aim of the present study was to investigate the effectiveness of the miR-17-92 cluster as a disease progression marker in prostate cancer (PCa). Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the microRNA (miR)-17-92 cluster expression levels in tissues from patients with PCa or benign prostatic hyperplasia (BPH), in addition to in PCa and BPH cell lines. Spearman correlation was used for comparison and estimation of correlations between miRNA expression levels and clinicopathological characteristics such as the Gleason score and prostate-specific antigen (PSA). Receiver operating curve (ROC) analysis was performed for evaluation of specificity and sensitivity of miR-17-92 cluster expression levels for discriminating patients with PCa from patients with BPH. Kaplan-Meier analysis was plotted to investigate the predictive potential of miR-17-92 cluster for PCa biochemical recurrence. Expression of the majority of miRNAs in the miR-17-92 cluster was identified to be significantly increased in PCa tissues and cell lines. Bivariate correlation analysis indicated that the high expression of unregulated miRNAs was positively correlated with Gleason grade, but had no significant association with PSA. ROC curves demonstrated that high expression of miR-17-92 cluster predicted a higher diagnostic accuracy compared with PSA. Improved discriminating quotients were observed when combinations of unregulated miRNAs with PSA were used. Survival analysis confirmed a high combined miRNA score of miR-17-92 cluster was associated with shorter biochemical recurrence interval. miR-17-92 cluster could be a potential diagnostic and prognostic biomarker for PCa, and the combination of the miR-17-92 cluster and serum PSA may enhance the accuracy for diagnosis of PCa.

Physical activity and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

DEFF Research Database (Denmark)

Johnsen, Nina Føns; Tjønneland, Anne; Thomsen, Birthe L R

2009-01-01

incidence rate and occupational activity and leisure time activity in terms of participation in sports, cycling, walking and gardening; a metabolic equivalent (MET) score based on weekly time spent on the 4 activities; and a physical activity index. MET hours per week of leisure time activity, higher score......The evidence concerning the possible association between physical activity and the risk of prostate cancer is inconsistent and additional data are needed. We examined the association between risk of prostate cancer and physical activity at work and in leisure time in the European Prospective...... in the physical activity index, participation in any of the 4 leisure time activities, and the number of leisure time activities in which the participants were active were not associated with prostate cancer incidence. However, higher level of occupational physical activity was associated with lower risk...

OBSERVED SCALING RELATIONS FOR STRONG LENSING CLUSTERS: CONSEQUENCES FOR COSMOLOGY AND CLUSTER ASSEMBLY

International Nuclear Information System (INIS)

Comerford, Julia M.; Moustakas, Leonidas A.; Natarajan, Priyamvada

2010-01-01

Scaling relations of observed galaxy cluster properties are useful tools for constraining cosmological parameters as well as cluster formation histories. One of the key cosmological parameters, σ 8 , is constrained using observed clusters of galaxies, although current estimates of σ 8 from the scaling relations of dynamically relaxed galaxy clusters are limited by the large scatter in the observed cluster mass-temperature (M-T) relation. With a sample of eight strong lensing clusters at 0.3 8 , but combining the cluster concentration-mass relation with the M-T relation enables the inclusion of unrelaxed clusters as well. Thus, the resultant gains in the accuracy of σ 8 measurements from clusters are twofold: the errors on σ 8 are reduced and the cluster sample size is increased. Therefore, the statistics on σ 8 determination from clusters are greatly improved by the inclusion of unrelaxed clusters. Exploring cluster scaling relations further, we find that the correlation between brightest cluster galaxy (BCG) luminosity and cluster mass offers insight into the assembly histories of clusters. We find preliminary evidence for a steeper BCG luminosity-cluster mass relation for strong lensing clusters than the general cluster population, hinting that strong lensing clusters may have had more active merging histories.

Performance of activities of daily living among hospitalized cancer patients

DEFF Research Database (Denmark)

Lindahl-Jacobsen, Line; Hansen, Dorte Gilså; Wæhrens, Eva Ejlersen

2015-01-01

and characterize ADL task performance problems among a group of adult disabled hospitalized cancer patients using interview and questionnaire data. METHODS: Cross-sectional study on prevalence of ADL task performance problems experienced by disabled hospitalized cancer patients using the Activities of Daily Living...... Questionnaire (ADL-Q) (n = 118) and the Canadian Occupational Performance Measure (COPM) (n = 55). RESULTS: All 118 patients reported problems with ADL task performance. Based on the ADL-Q patients reported more problems within instrumental (I-)ADL than personal (P-)ADL. In both I-ADL and P-ADL the results......BACKGROUND: Many cancer patients report unmet rehabilitation needs. Rehabilitation may include activities of daily living (ADL) tasks, but little is known about how cancer patients perform these tasks and how they prioritize their daily activities. Hence, this study aims to identify...

Minimizing the cancer-promotional activity of cox-2 as a central strategy in cancer prevention.

Science.gov (United States)

McCarty, Mark F

2012-01-01

A recent meta-analysis examining long-term mortality in subjects who participated in controlled studies evaluating the impact of daily aspirin on vascular risk, has concluded that aspirin confers substantial protection from cancer mortality. Remarkably, low-dose aspirin was as effective as higher-dose regimens; hence this protection may be achievable with minimal risk. There is reason to believe that this protection stems primarily from inhibition of cox-2 in pre-neoplastic lesions. Since safe aspirin regimens can only achieve a partial and transitory inhibition of cox-2, it may be feasible to complement the cancer-protective benefit of aspirin with other measures which decrease cox-2 expression or which limit the bioactivity of cox-2-derived PGE2. Oxidative stress boosts cox-2 expression by up-regulating activation of NF-kappaB and MAP kinases; NADPH oxidase activation may thus promote carcinogenesis by increasing cox-2 expression while also amplifying oxidant-mediated mutagenesis. A prospective cohort study has observed that relatively elevated serum bilirubin levels are associated with a marked reduction in subsequent cancer mortality; this may reflect bilirubin's physiological role as a potent inhibitor of NADPH oxidase. It may be feasible to mimic this protective effect by supplementing with spirulina, a rich source of a phycobilin which shares bilirubin's ability to inhibit NADPH oxidase. Ancillary antioxidant measures - phase 2 inducing phytochemicals, melatonin, N-acetylcysteine, and astaxanthin - may also aid cox-2 down-regulation. The cancer protection often associated with high-normal vitamin D status may be attributable, in part, to the ability of the activated vitamin D receptor to decrease cox-2 expression while promoting PGE2 catabolism and suppressing the expression of PGE2 receptors. Diets with a relatively low ratio of omega-6 to long-chain omega-3 fats may achieve cancer protection by antagonizing the production and bioactivity of PGE2. Growth

General Practitioners' Barriers to Prescribe Physical Activity: The Dark Side of the Cluster Effects on the Physical Activity of Their Type 2 Diabetes Patients.

Science.gov (United States)

Lanhers, Charlotte; Duclos, Martine; Guttmann, Aline; Coudeyre, Emmanuel; Pereira, Bruno; Ouchchane, Lemlih

2015-01-01

To describe barriers to physical activity (PA) in type 2 diabetes patients and their general practitioners (GPs), looking for practitioner's influence on PA practice of their patients. We conducted a cross-sectional study on GPs (n = 48) and their type 2 diabetes patients (n = 369) measuring respectively barriers to prescribe and practice PA using a self-assessment questionnaire: barriers to physical activity in diabetes (BAPAD). Statistical analysis was performed accounting hierarchical data structure. Similar practitioner's patients were considered a cluster sharing common patterns. The higher the patient's BAPAD score, the higher the barriers to PA, the higher the risk to declare practicing no PA (pbarriers to physical activity, have a higher PA level and a better glycemic control. An important and deleterious cluster effect between GPs and their patients is demonstrated: the higher the GP's BAPAD score, the higher the type 2 diabetes patients' BAPAD score. This important cluster effect might designate GPs as a relevant lever for future interventions regarding patient's education towards PA and type 2 diabetes management.

AR-V7 in circulating tumor cells cluster as a predictive biomarker of abiraterone acetate and enzalutamide treatment in castration-resistant prostate cancer patients.

Science.gov (United States)

Okegawa, Takatsugu; Ninomiya, Naoki; Masuda, Kazuki; Nakamura, Yu; Tambo, Mitsuhiro; Nutahara, Kikuo

2018-06-01

We examined whether androgen receptor splice variant 7 (AR-V7) in circulating tumor cell(CTC)clusters can be used to predict survival in patients with bone metastatic castration resistant-prostate cancer (mCRPC) treated with abiraterone or enzalutamide. We retrospectively enrolled 98 patients with CRPC on abiraterone or enzalutamide, and investigated the prognostic value of CTC cluster detection (+ v -) and AR-V7 detection (+ v -) using a CTC cluster detection - based AR-V7 mRNA assay. We examined ≤50% prostate-specific antigen (PSA) responses, PSA progression-free survival (PSA-PFS), clinical and radiological progression-free survival (radiologic PSF), and overall survival (OS). We then assessed whether AR-V7 expression in CTC clusters identified after On-chip multi-imaging flow cytometry was related to disease progression and survival after first-line systemic therapy. All abiraterone-treated or enzalutamide-treated patients received prior docetaxel. The median follow-up was 20.7 (range: 3.0-37.0) months in the abiraterone and enzalutamide cohorts, respectively. Forty-nine of the 98 men (50.0%) were CTC cluster (-), 23 of the 98 men (23.5%) were CTC cluster(+)/AR-V7(-), and 26 of the 98 men (26.5%) were CTC cluster(+)/AR-V7(+). CTC cluster(+)/AR-V7(+) patients were more likely to have EOD ≥3 at diagnosis (P = 0.003), pain (P = 0.023), higher alkaline phosphatase levels (P cluster(+), CTC cluster(+)/AR-V7(-), and ALP >UNL were independently associated with a poor PSA-PFS, radiographic PFS, and OS in abiraterone-treated patients and enzalutamide-treated patients. The CTC clusters and AR-V7-positive CTC clusters detected were important for assessing the response to abiraterone or enzalutamide therapy and for predicting disease outcome. © 2018 Wiley Periodicals, Inc.

Role of paramagnetic polyconjugated clusters in lignin antioxidant activity (in vitro)

International Nuclear Information System (INIS)

Dizhbite, T; Ponomarenko, J; Andersone, A; Dobele, G; Lauberts, M; Krasilnikova, J; Telysheva, G; Mironova-Ulmane, N

2012-01-01

Using physico-chemical methods (EPR, SEC, Py-GC/MS and UV/VIS spectroscopy) and wet chemical analysis, the characteristics of 6 hardwood lignins in terms of functionality, molecular weight and composition of lignin substructures were determined and considered together with the results of DPPH., ABTS. + and O 2 . − antioxidant assays with the aim to understand the relationships governing antioxidant properties of lignin. The strong positive linear correlation between lignin antioxidant capacity in the three assays used and the extent of conjugation of paramagnetic polyconjugated clusters in lignin macromolecules was found. The biological activity of the most active alkaline lignins was assessed by in vitro experiment with human blood.

Presence of urokinase plasminogen activator, its inhibitor and receptor in small cell lung cancer and non-small cell lung cancer

DEFF Research Database (Denmark)

Pappot, H.; Pfeiffer, P.; Grøndahl Hansen, J.

1997-01-01

Spreading of cancer cells is dependent on the combined action of several proteolytic enzymes, such as serine proteases, comprising the urokinase pathway of plasminogen activation. Previous studies of lung cancer indicate that expression, localization and prognostic impact of the components...... of the plasminogen activation system differ in the different non-small cell lung cancer (NSCLC) types, whereas the expression of the components in small cell lung cancer (SCLC) has only sparingly been investigated. In the present study we investigate the presence of the components of the plasminogen activation...... that the plasminogen activation system could play a role in this type of cancer during invasion. In addition a difference in the levels of the components of the plasminogen activation system in NSCLC and SCLC is found, which could contribute to the differences in biology....

P52 Activation and Enzalutamide Therapy in Prostate Cancer

Science.gov (United States)

2017-10-01

c-Myc:hnRNPA1 pathway regulates expression of androgen receptor splice variants and enzalutamide sensitivity in prostate cancer . Castration resistant... prostate cancer (CRPC) remains dependent on androgen receptor (AR) signaling. Alternative splicing of the AR to generate constitutively active... receptor splice variants and enzalutamide sensitivity in prostate cancer . • We discovered that quercetin, a naturally occurring polyphenolic compound

Distinct profile of vascular progenitor attachment to extracellular matrix proteins in cancer patients.

Science.gov (United States)

Labonté, Laura; Li, Yuhua; Addison, Christina L; Brand, Marjorie; Javidnia, Hedyeh; Corsten, Martin; Burns, Kevin; Allan, David S

2012-04-01

Vascular progenitor cells (VPCs) facilitate angiogenesis and initiate vascular repair by homing in on sites of damage and adhering to extracellular matrix (ECM) proteins. VPCs also contribute to tumor angiogenesis and induce angiogenic switching in sites of metastatic cancer. In this study, the binding of attaching cells in VPC clusters that form in vitro on specific ECM proteins was investigated. VPC cluster assays were performed in vitro on ECM proteins enriched in cancer cells and in remodelling tissue. Profiles of VPC clusters from patients with cancer were compared to healthy controls. The role of VEGF and integrin-specific binding of angiogenic attaching cells was addressed. VPC clusters from cancer patients were markedly increased on fibronectin relative to other ECM proteins tested, in contrast to VPC clusters from control subjects, which formed preferentially on laminin. Specific integrin-mediated binding of attaching cells in VPC clusters was matrix protein-dependent. Furthermore, cancer patients had elevated plasma VEGF levels compared to healthy controls and VEGF facilitated preferential VPC cluster formation on fibronectin. Incubating cells from healthy controls with VEGF induced a switch from the 'healthy' VPC binding profile to the profile observed in cancer patients with a marked increase in VPC cluster formation on fibronectin. The ECM proteins laminin and fibronectin support VPC cluster formation via specific integrins on attaching cells and can facilitate patterns of VPC cluster formation that are distinct in cancer patients. Larger studies, however, are needed to gain insight on how tumor angiogenesis may differ from normal repair processes.

An assessment of Prostate Cancer Research International: Active Surveillance (PRIAS) criteria for active surveillance of clinically low-risk prostate cancer patients

Science.gov (United States)

da Silva, Vitor; Cagiannos, Ilias; Lavallée, Luke T.; Mallick, Ranjeeta; Witiuk, Kelsey; Cnossen, Sonya; Eastham, James A.; Fergusson, Dean A.; Morash, Chris; Breau, Rodney H.

2017-01-01

Introduction Active surveillance is a strategy to delay or prevent treatment of indolent prostate cancer. The Prostate Cancer Research International: Active Surveillance (PRIAS) criteria were developed to select patients for prostate cancer active surveillance. The objective of this study was to compare pathological findings from PRIAS-eligible and PRIAS-ineligible clinically low-risk prostate cancer patients. Methods A D’Amico low-risk cohort of 1512 radical prostatectomy patients treated at The Ottawa Hospital or Memorial Sloan Kettering Cancer Centre between January 1995 and December 2007 was reviewed. Pathological outcomes (pT3 tumours, Gleason sum ≥7, lymph node metastases, or a composite) and clinical outcomes (prostate-specific antigen [PSA] recurrence, secondary cancer treatments, and death) were compared between PRIAS-eligible and PRIAS-ineligible cohorts. Results The PRIAS-eligible cohort (n=945) was less likely to have Gleason score ≥7 (odds ratio [OR] 0.61; 95% confidence interval [CI] 0.49–0.75), pT3 (OR 0.41; 95% CI 0.31–0.55), nodal metastases (OR 0.37; 95% CI 0.10–1.31), or any adverse feature (OR 0.56; 95% CI 0.45–0.69) compared to the PRIAS-ineligible cohort. The probability of any adverse pathology in the PRIAS-eligible cohort was 41% vs. 56% in the PRIAS-ineligible cohort. At median follow-up of 3.7 years, 72 (4.8%) patients had a PSA recurrence, 24 (1.6%) received pelvic radiation, and 13 (0.9%) received androgen deprivation. No difference was detected for recurrence-free and overall survival between groups (recurrence hazard ratio [HR] 0.71; 95% CI 0.46–1.09 and survival HR 0.72; 95% CI 0.36–1.47). Conclusions Low-risk prostate cancer patients who met PRIAS eligibility criteria are less likely to have higher-risk cancer compared to those who did not meet at least one of these criteria. PMID:28798822

Beyond recreational physical activity: examining occupational and household activity, transportation activity, and sedentary behavior in relation to postmenopausal breast cancer risk.

Science.gov (United States)

George, Stephanie M; Irwin, Melinda L; Matthews, Charles E; Mayne, Susan T; Gail, Mitchell H; Moore, Steven C; Albanes, Demetrius; Ballard-Barbash, Rachel; Hollenbeck, Albert R; Schatzkin, Arthur; Leitzmann, Michael F

2010-11-01

We prospectively examined nonrecreational physical activity and sedentary behavior in relation to breast cancer risk among 97 039 postmenopausal women in the National Institutes of Health-AARP Diet and Health Study. We identified 2866 invasive and 570 in situ breast cancer cases recorded between 1996 and 2003 and used Cox proportional hazards regression to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs). Routine activity during the day at work or at home that included heavy lifting or carrying versus mostly sitting was associated with reduced risk of invasive breast cancer (RR = 0.62; 95% CI = 0.42, 0.91; P(trend) = .024). Routine activity during the day at work or home may be related to reduced invasive breast cancer risk. Domains outside of recreation time may be attractive targets for increasing physical activity and reducing sedentary behavior among postmenopausal women.

The Effect of Personal Characteristics, Perceived Threat, Efficacy and Breast Cancer Anxiety on Breast Cancer Screening Activation

OpenAIRE

De Pelsmacker, Patrick; Lewi, Martine; Cauberghe, Veroline

2017-01-01

Abstract: In order to activate women to participate in breast cancer screening programs, a good understanding is needed of the personal characteristics that influence how women can be activated to search for more information, consult friends and doctors, and participate in breast cancer screening programs. In the current study, we investigate the effect of six personal characteristics that have in previous research been identified as important triggers of health behavior on breast cancer scre...

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil; Kaur, Mandeep; Minneman, Kenneth P.; Bajic, Vladimir B.

2010-01-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

Anti-cancer activities of diospyrin, its derivatives and analogues

KAUST Repository

Sagar, Sunil

2010-09-01

Natural products have played a vital role in drug discovery and development process for cancer. Diospyrin, a plant based bisnaphthoquinonoid, has been used as a lead molecule in an effort to develop anti-cancer drugs. Several derivatives/analogues have been synthesized and screened for their pro-apoptotic/anti-cancer activities so far. Our review is focused on the pro-apoptotic/anti-cancer activities of diospyrin, its derivatives/analogues and the different mechanisms potentially involved in the bioactivity of these compounds. Particular focus has been placed on the different mechanisms (both chemical and molecular) thought to underlie the bioactivity of these compounds. A brief bioinformatics analysis at the end of the article provides novel insights into the new potential mechanisms and pathways by which these compounds might exert their effects and lead to a better realization of the full therapeutic potential of these compounds as anti-cancer drugs. © 2010 Elsevier Masson SAS. All rights reserved.

Physical activity and risk of prostate and bladder cancer in China: The South and East China case-control study on prostate and bladder cancer.

Directory of Open Access Journals (Sweden)

Raoul C Reulen

Full Text Available Recent meta-analyses have suggested a modest protective effect of high levels of physical activity on developing both prostate and bladder cancer, but significant heterogeneity between studies included in these meta-analyses existed. To our knowledge, few Chinese studies investigated the association between physical activity and prostate cancer and none between physical activity and bladder cancer. Given the inconsistencies between previous studies and because studies on the relation between physical activity and prostate and bladder cancer in China are scarce, it remains elusive whether there is a relationship between physical activity and prostate and bladder cancer within the Chinese population.We investigated the association between physical activity and risk of developing prostate and bladder cancer within a hospital-based case-control study in the East and South of China among 260 and 438 incident prostate and bladder cancer cases, respectively, and 427 controls. A questionnaire was administered to measure physical activity as metabolic equivalents (METs. Random effects logistic regression was used to calculate odds ratios (ORs of prostate and bladder cancer for different levels of physical activity and for the specific activities of walking and cycling.Increasing overall physical activity was associated with a significant reduction in prostate cancer risk (Ptrend = 0.04 with the highest activity tertile level showing a nearly 50% reduction in prostate cancer risk (OR = 0.53, 95%CI: 0.28-0.98. Overall physical activity was not significantly associated with risk of bladder cancer (Ptrend = 0.61, neither were vigorous (Ptrend = 0.60 or moderate levels of physical activity (Ptrend = 0.21. Walking and cycling were not significantly associated with either prostate (Ptrend> = 0.62 or bladder cancer risk (Ptrend> = 0.25.The findings of this largest ever case-control study in China investigating the relationship between physical activity and

Behavioural graded activity results in better exercise adherence and more physical activity than usual care in people with osteoarthritis: a cluster-randomised trial

NARCIS (Netherlands)

Pisters, M.F.; Veenhof, C.; de Bakker, D.H.; Schellevis, F.G.; Dekker, J.

2010-01-01

Question: Does behavioural graded activity result in better exercise adherence and more physical activity than usual care in people with osteoarthritis of the hip or knee? Design: Analysis of secondary outcomes of a cluster-randomised trial with concealed allocation, assessor blinding, and

Activation of the hedgehog pathway in advanced prostate cancer

Directory of Open Access Journals (Sweden)

McCormick Frank

2004-10-01

Full Text Available Abstract Background The hedgehog pathway plays a critical role in the development of prostate. However, the role of the hedgehog pathway in prostate cancer is not clear. Prostate cancer is the second most prevalent cause of cancer death in American men. Therefore, identification of novel therapeutic targets for prostate cancer has significant clinical implications. Results Here we report that activation of the hedgehog pathway occurs frequently in advanced human prostate cancer. We find that high levels of hedgehog target genes, PTCH1 and hedgehog-interacting protein (HIP, are detected in over 70% of prostate tumors with Gleason scores 8–10, but in only 22% of tumors with Gleason scores 3–6. Furthermore, four available metastatic tumors all have high expression of PTCH1 and HIP. To identify the mechanism of the hedgehog signaling activation, we examine expression of Su(Fu protein, a negative regulator of the hedgehog pathway. We find that Su(Fu protein is undetectable in 11 of 27 PTCH1 positive tumors, two of them contain somatic loss-of-function mutations of Su(Fu. Furthermore, expression of sonic hedgehog protein is detected in majority of PTCH1 positive tumors (24 out of 27. High levels of hedgehog target genes are also detected in four prostate cancer cell lines (TSU, DU145, LN-Cap and PC3. We demonstrate that inhibition of hedgehog signaling by smoothened antagonist, cyclopamine, suppresses hedgehog signaling, down-regulates cell invasiveness and induces apoptosis. In addition, cancer cells expressing Gli1 under the CMV promoter are resistant to cyclopamine-mediated apoptosis. All these data suggest a significant role of the hedgehog pathway for cellular functions of prostate cancer cells. Conclusion Our data indicate that activation of the hedgehog pathway, through loss of Su(Fu or overexpression of sonic hedgehog, may involve tumor progression and metastases of prostate cancer. Thus, targeted inhibition of hedgehog signaling may have

Characterization of low active ghrelin ratio in patients with advanced pancreatic cancer.

Science.gov (United States)

Miura, Tomofumi; Mitsunaga, Shuichi; Ikeda, Masafumi; Ohno, Izumi; Takahashi, Hideaki; Suzuki, Hidetaka; Irisawa, Ai; Kuwata, Takeshi; Ochiai, Atsushi

2018-05-18

Acyl ghrelin is an orexigenic peptide. Active ghrelin ratio, the ratio of acyl ghrelin to total ghrelin, has an important role in physiological functions and gastrointestinal symptoms. However, low active ghrelin ratio-related characteristics, gastrointestinal symptoms, and chemotherapy-induced gastrointestinal toxicity in patients with advanced pancreatic cancer have not been previously evaluated. The goal of this study was to identify low active ghrelin ratio-related factors in treatment-naïve advanced pancreatic cancer patients. Patients with treatment-naïve advanced pancreatic cancer were eligible for inclusion in this study. Active ghrelin ratio and clinical parameters of patients were prospectively recorded. Factors correlated with low active ghrelin ratio and survival were analyzed. In total, 92 patients were analyzed. Low active ghrelin ratio-related factors were advanced age (P advanced pancreatic cancer.

Physical Activity and Cervical Cancer Testing among American Indian Women

Science.gov (United States)

Muus, Kyle J.; Baker-Demaray, Twyla B.; Bogart, T. Andy; Duncan, Glen E.; Jacobsen, Clemma; Buchwald, Dedra S.; Henderson, Jeffrey A.

2012-01-01

Purpose: Studies have shown that women who engage in high levels of physical activity have higher rates of cancer screening, including Papanicalaou (Pap) tests. Because American Indian (AI) women are at high risk for cervical cancer morbidity and mortality, we examined Pap screening prevalence and assessed whether physical activity was associated…

The N2O activation by Rh5 clusters. A quantum chemistry study.

Science.gov (United States)

Olvera-Neria, Oscar; Avilés, Roberto; Francisco-Rodríguez, Héctor; Bertin, Virineya; García-Cruz, Raúl; González-Torres, Julio César; Poulain, Enrique

2015-04-01

Nitrous oxide (N2O) is a by-product of exhaust pipe gases treatment produced by motor vehicles. Therefore, the N2O reduction to N2 is necessary to meet the actual environmental legislation. The N2O adsorption and dissociation assisted by the square-based pyramidal Rh5 cluster was investigated using the density functional theory and the zero-order regular approximation (ZORA). The Rh5 sextet ground state is the most active in N2O dissociation, though the quartet and octet states are also active because they are degenerate. The Rh5 cluster spontaneously activates the N2─O cleavage, and the reaction is highly exothermic ca. -75 kcal mol(-1). The N2─O breaking is obtained for the geometrical arrangement that maximizes the overlap and electron transfers between the N2O and Rh5 frontier orbitals. The Rh5 high activity is due to the Rh 3d orbitals are located between the N2O HOMO and LUMO orbitals, which makes possible the interactions between them. In particular, the O 2p states strongly interact with Rh 3d orbitals, which finally weaken the N2─O bond. The electron transfer is from the Rh5 HOMO orbital to the N2O antibonding orbital.

Cancer control activities in the Republic of Korea.

Science.gov (United States)

Yoo, Keun-Young

2008-05-01

South Korea has a population of 47.3 million. The whole population is covered by a mandatory social insurance system (the National Health Insurance Program) that is financed through the contributions paid by the insured and their employers. Cancer has been the leading cause of death in Korea since 1983. About 130 000 people develop cancer annually with 66 000 deaths in 2006. Cancer patients' 5-year survival rates between 1998 and 2002 were 37.8 and 57.0% for men and women, respectively. The five leading primary cancer sites were stomach, lung, liver, colon and rectum, and bladder among males, whereas the most common cancers were stomach, breast, colon and rectum, uterine cervix and lung among females. With the rapidly aging population, reducing cancer burden at the national level has become one of the major political issues in Korea. The government formulated its first 10-year plan for cancer control in 1996. In 2000, the National Cancer Center was created and the Cancer Control Division was set up within the Ministry of Health and Welfare. The Cancer Control Act was legislated in 2003. Korea's major national cancer control programs are anti-smoking campaigns, hepatitis B virus vaccination, cancer registration and networking, promotion of R&D activities for cancer control, education and training for cancer control and prevention, operation of the national cancer information center, operation of the mass screening program for five common cancers, management of cancer patients at home, financial support for cancer patients and designation of regional cancer centers.

Cluster size matters: Size-driven performance of subnanometer clusters in catalysis, electrocatalysis and Li-air batteries

Science.gov (United States)

Vajda, Stefan

2015-03-01

This paper discusses the strongly size-dependent performance of subnanometer cluster based catalysts in 1) heterogeneous catalysis, 2) electrocatalysis and 3) Li-air batteries. The experimental studies are based on I. fabrication of ultrasmall clusters with atomic precision control of particle size and their deposition on oxide and carbon based supports; II. test of performance, III. in situand ex situ X-ray characterization of cluster size, shape and oxidation state; and IV.electron microscopies. Heterogeneous catalysis. The pronounced effect of cluster size and support on the performance of the catalyst (catalyst activity and the yield of Cn products) will be illustrated on the example of nickel and cobalt clusters in Fischer-Tropsch reaction. Electrocatalysis. The study of the oxygen evolution reaction (OER) on size-selected palladium clusters supported on ultrananocrystalline diamond show pronounced size effects. While Pd4 clusters show no reaction, Pd6 and Pd17 clusters are among the most active catalysts known (in in terms of turnover rate per Pd atom). The system (soft-landed Pd4, Pd6, or Pd17 clusters on an UNCD Si coated electrode) shows stable electrochemical potentials over several cycles, and the characterization of the electrodes show no evidence for evolution or dissolution of either the support Theoretical calculations suggest that this striking difference may be a demonstration that bridging Pd-Pd sites, which are only present in three-dimensional clusters, are active for the oxygen evolution reaction in Pd6O6. Li-air batteries. The studies show that sub-nm silver clusters have dramatic size-dependent effect on the lowering of the overpotential, charge capacity, morphology of the discharge products, as well as on the morphology of the nm size building blocks of the discharge products. The results suggest that by precise control of the active surface sites on the cathode, the performance of Li-air cells can be significantly improved

Novel strategy to implement active-space coupled-cluster methods

Science.gov (United States)

Rolik, Zoltán; Kállay, Mihály

2018-03-01

A new approach is presented for the efficient implementation of coupled-cluster (CC) methods including higher excitations based on a molecular orbital space partitioned into active and inactive orbitals. In the new framework, the string representation of amplitudes and intermediates is used as long as it is beneficial, but the contractions are evaluated as matrix products. Using a new diagrammatic technique, the CC equations are represented in a compact form due to the string notations we introduced. As an application of these ideas, a new automated implementation of the single-reference-based multi-reference CC equations is presented for arbitrary excitation levels. The new program can be considered as an improvement over the previous implementations in many respects; e.g., diagram contributions are evaluated by efficient vectorized subroutines. Timings for test calculations for various complete active-space problems are presented. As an application of the new code, the weak interactions in the Be dimer were studied.

Cytotoxic activity of erypogein d from erythrina poeppigiana (leguminosae) against cervical cancer (HeLa), breast cancer (MCF-7) and ovarian cancer (SKOV-3) cells

Science.gov (United States)

Herlina, T.; Gaffar, S.; Widowati, W.

2018-05-01

Cancer is the uncontrolled growth of abnormal cells and continues to divide rapidly in the body. Current anticancer treatment usually causes many side effects. Natural products are then explored to be new alternatives for cancer treatment. Flavonoids have been known to possess medicinal properties, including anticancer. This study was performed to observe the cytotoxic activity of isoflavanone compound, erypogein D from Erythrina poeppigiana, toward cervical cancer (HeLa), breast cancer (MCF-7) and ovarian cancer (SKOV-3) cells. The cytotoxic activity of erypogein D was tested using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxyme-thoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. The percentage of cell mortality was calculated and the IC50 was analyzed using probit analysis. The result showed that cytotoxic activity of the erypogein D against HeLa, SKOV-3, and MCF-7 cells had an IC50 value 225, 70.74, and 30.12 μM, respectively. Based on IC50 value can be concluded that erypogein D is the most cytotoxic to breast cancer MCF-7 cell. However the cytotoxic activity of erypogein D toward MCF7 is moderate.

HER2 activating mutations are targets for colorectal cancer treatment.

Science.gov (United States)

Kavuri, Shyam M; Jain, Naveen; Galimi, Francesco; Cottino, Francesca; Leto, Simonetta M; Migliardi, Giorgia; Searleman, Adam C; Shen, Wei; Monsey, John; Trusolino, Livio; Jacobs, Samuel A; Bertotti, Andrea; Bose, Ron

2015-08-01

The Cancer Genome Atlas project identified HER2 somatic mutations and gene amplification in 7% of patients with colorectal cancer. Introduction of the HER2 mutations S310F, L755S, V777L, V842I, and L866M into colon epithelial cells increased signaling pathways and anchorage-independent cell growth, indicating that they are activating mutations. Introduction of these HER2 activating mutations into colorectal cancer cell lines produced resistance to cetuximab and panitumumab by sustaining MAPK phosphorylation. HER2 mutants are potently inhibited by low nanomolar doses of the irreversible tyrosine kinase inhibitors neratinib and afatinib. HER2 gene sequencing of 48 cetuximab-resistant, quadruple (KRAS, NRAS, BRAF, and PIK3CA) wild-type (WT) colorectal cancer patient-derived xenografts (PDX) identified 4 PDXs with HER2 mutations. HER2-targeted therapies were tested on two PDXs. Treatment with a single HER2-targeted drug (trastuzumab, neratinib, or lapatinib) delayed tumor growth, but dual HER2-targeted therapy with trastuzumab plus tyrosine kinase inhibitors produced regression of these HER2-mutated PDXs. HER2 activating mutations cause EGFR antibody resistance in colorectal cell lines, and PDXs with HER2 mutations show durable tumor regression when treated with dual HER2-targeted therapy. These data provide a strong preclinical rationale for clinical trials targeting HER2 activating mutations in metastatic colorectal cancer. ©2015 American Association for Cancer Research.

Epidemiologic studies of radioactively contaminated environments and cancer clusters

International Nuclear Information System (INIS)

Boice, J.D. Jr.

1991-01-01

This paper reports on epidemiologic studies which address the distribution and determinants of disease in human populations. Investigations of the possible adverse effects of living in radioactively contaminated environments are difficult to conduct, however, because human populations tend to be fairly mobile, cumulative exposures to individuals from environmental conditions are difficult to estimate, and the risks associated with such exposures tend to be small relative to background levels of disease. Such studies can be arbitrarily classified as geographic correlation surveys, analytic studies, and cluster evaluations. Geographic correlation studies (ecological surveys) relate disease in populations to area characteristics. Although exposure to individuals is unknown, these exploratory or hypothesis-generating studies can identify areas to target for further in-depth evaluation. Analytic investigations relate individual exposure information to disease occurrence. Unusual occurrences of disease in time and place (clusters) occasionally point to a common environmental factor; cluster evaluations have been most successful in identifying the source of infectious disease outbreaks

Reactivity and Catalytic Activity of Hydrogen Atom Chemisorbed Silver Clusters.

Science.gov (United States)

Manzoor, Dar; Pal, Sourav

2015-06-18

Metal clusters of silver have attracted recent interest of researchers as a result of their potential in different catalytic applications and low cost. However, due to the completely filled d orbital and very high first ionization potential of the silver atom, the silver-based catalysts interact very weakly with the reacting molecules. In the current work, density functional theory calculations were carried out to investigate the effect of hydrogen atom chemisorption on the reactivity and catalytic properties of inert silver clusters. Our results affirm that the hydrogen atom chemisorption leads to enhancement in the binding energy of the adsorbed O2 molecule on the inert silver clusters. The increase in the binding energy is also characterized by the decrease in the Ag-O and increase in the O-O bond lengths in the case of the AgnH silver clusters. Pertinent to the increase in the O-O bond length, a significant red shift in the O-O stretching frequency is also noted in the case of the AgnH silver clusters. Moreover, the hydrogen atom chemisorbed silver clusters show low reaction barriers and high heat of formation of the final products for the environmentally important CO oxidation reaction as compared to the parent catalytically inactive clusters. The obtained results were compared with those of the corresponding gold and hydrogen atom chemisorbed gold clusters obtained at the same level of theory. It is expected the current computational study will provide key insights for future advances in the design of efficient nanosilver-based catalysts through the adsorption of a small atom or a ligand.

Cancer as a complex phenotype: pattern of cancer distribution within and beyond the nuclear family.

Directory of Open Access Journals (Sweden)

Laufey T Amundadottir

2004-12-01

Full Text Available BACKGROUND: The contribution of low-penetrant susceptibility variants to cancer is not clear. With the aim of searching for genetic factors that contribute to cancer at one or more sites in the body, we have analyzed familial aggregation of cancer in extended families based on all cancer cases diagnosed in Iceland over almost half a century. METHODS AND FINDINGS: We have estimated risk ratios (RRs of cancer for first- and up to fifth-degree relatives both within and between all types of cancers diagnosed in Iceland from 1955 to 2002 by linking patient information from the Icelandic Cancer Registry to an extensive genealogical database, containing all living Icelanders and most of their ancestors since the settlement of Iceland. We evaluated the significance of the familial clustering for each relationship separately, all relationships combined (first- to fifth-degree relatives and for close (first- and second-degree and distant (third- to fifth-degree relatives. Most cancer sites demonstrate a significantly increased RR for the same cancer, beyond the nuclear family. Significantly increased familial clustering between different cancer sites is also documented in both close and distant relatives. Some of these associations have been suggested previously but others not. CONCLUSION: We conclude that genetic factors are involved in the etiology of many cancers and that these factors are in some cases shared by different cancer sites. However, a significantly increased RR conferred upon mates of patients with cancer at some sites indicates that shared environment or nonrandom mating for certain risk factors also play a role in the familial clustering of cancer. Our results indicate that cancer is a complex, often non-site-specific disease for which increased risk extends beyond the nuclear family.

Development of on-chip multi-imaging flow cytometry for identification of imaging biomarkers of clustered circulating tumor cells.

Directory of Open Access Journals (Sweden)

Hyonchol Kim

Full Text Available An on-chip multi-imaging flow cytometry system has been developed to obtain morphometric parameters of cell clusters such as cell number, perimeter, total cross-sectional area, number of nuclei and size of clusters as "imaging biomarkers", with simultaneous acquisition and analysis of both bright-field (BF and fluorescent (FL images at 200 frames per second (fps; by using this system, we examined the effectiveness of using imaging biomarkers for the identification of clustered circulating tumor cells (CTCs. Sample blood of rats in which a prostate cancer cell line (MAT-LyLu had been pre-implanted was applied to a microchannel on a disposable microchip after staining the nuclei using fluorescent dye for their visualization, and the acquired images were measured and compared with those of healthy rats. In terms of the results, clustered cells having (1 cell area larger than 200 µm2 and (2 nucleus area larger than 90 µm2 were specifically observed in cancer cell-implanted blood, but were not observed in healthy rats. In addition, (3 clusters having more than 3 nuclei were specific for cancer-implanted blood and (4 a ratio between the actual perimeter and the perimeter calculated from the obtained area, which reflects a shape distorted from ideal roundness, of less than 0.90 was specific for all clusters having more than 3 nuclei and was also specific for cancer-implanted blood. The collected clusters larger than 300 µm2 were examined by quantitative gene copy number assay, and were identified as being CTCs. These results indicate the usefulness of the imaging biomarkers for characterizing clusters, and all of the four examined imaging biomarkers-cluster area, nuclei area, nuclei number, and ratio of perimeter-can identify clustered CTCs in blood with the same level of preciseness using multi-imaging cytometry.

Large stability and high catalytic activities of sub-nm metal (0) clusters: implications into the nucleation and growth theory.

Science.gov (United States)

Piñeiro, Yolanda; Buceta, David; Calvo, Javier; Huseyinova, Shahana; Cuerva, Miguel; Pérez, Ángel; Domínguez, Blanca; López-Quintela, M Arturo

2015-07-01

Clusters are stable catalytic species, which are produced during the synthesis of nanoparticles (NPs). Their existence contradicts the thermodynamic principles used to explain the formation of NPs by the classical nucleation and growth theories (NGTs). Using chemical and electrochemical methods we will show that depending on the experimental conditions one can produce either Ag clusters or Ag NPs. Moreover, using already prepared Ag clusters one can observe the disappearance of the usual induction period observed for the kinetics of NP formation, indicating that clusters catalyze the formation of NPs. Taking these data together with some previous examples of cluster-catalyzed anisotropic growth, we derived a qualitative approach to include the catalytic activities of clusters into the formation of NPs, which is incorporated into the NGT. Some qualitative conclusions about the main experimental parameters, which affect the formation of clusters versus NPs, as well as the catalytic mechanism versus the non-catalytic one, are also described. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical Activity in General Practice and Cancer

DEFF Research Database (Denmark)

Hjertholm, Peter

2015-01-01

, and to analyse how a suspicion influenced the demand for health care services and predicted a future diagnosis of serious disease - to investigate whether variation in GPs’ diagnostic activity influences cancer patients’ prognosis in relation to prostate-specific antigen (PSA) testing and prostate cancer....... In the future, we need to learn to differentiate between indolent and aggressive prostate cancers. This may, again, leave room for PSA testing as a screening tool. Our findings do indicate a small positive effect of more lower endoscopies, which could be investigated in an intervention study where some GPs...... are randomised to a more liberal access to lower endoscopies. Alongside this, we need to keep on exploring alternative approaches including the use of iFOBT in symptomatic patients. Overall, this thesis indicates that the role of GPs in the diagnosis of cancer should be strengthened through easy access...

Voting-based consensus clustering for combining multiple clusterings of chemical structures

Directory of Open Access Journals (Sweden)

Saeed Faisal

2012-12-01

Full Text Available Abstract Background Although many consensus clustering methods have been successfully used for combining multiple classifiers in many areas such as machine learning, applied statistics, pattern recognition and bioinformatics, few consensus clustering methods have been applied for combining multiple clusterings of chemical structures. It is known that any individual clustering method will not always give the best results for all types of applications. So, in this paper, three voting and graph-based consensus clusterings were used for combining multiple clusterings of chemical structures to enhance the ability of separating biologically active molecules from inactive ones in each cluster. Results The cumulative voting-based aggregation algorithm (CVAA, cluster-based similarity partitioning algorithm (CSPA and hyper-graph partitioning algorithm (HGPA were examined. The F-measure and Quality Partition Index method (QPI were used to evaluate the clusterings and the results were compared to the Ward’s clustering method. The MDL Drug Data Report (MDDR dataset was used for experiments and was represented by two 2D fingerprints, ALOGP and ECFP_4. The performance of voting-based consensus clustering method outperformed the Ward’s method using F-measure and QPI method for both ALOGP and ECFP_4 fingerprints, while the graph-based consensus clustering methods outperformed the Ward’s method only for ALOGP using QPI. The Jaccard and Euclidean distance measures were the methods of choice to generate the ensembles, which give the highest values for both criteria. Conclusions The results of the experiments show that consensus clustering methods can improve the effectiveness of chemical structures clusterings. The cumulative voting-based aggregation algorithm (CVAA was the method of choice among consensus clustering methods.

Coagulation activation anc microparticle-associated coagulant activity in cancer patients An exploratory prospective study

NARCIS (Netherlands)

van Doormaal, Frederiek F.; Kleinjan, Ankie; Berckmans, René J.; Mackman, Nigel; Manly, David; Kamphuisen, Pieter W.; Richel, Dick J.; Büller, Harry R.; Sturk, Auguste; Nieuwland, Rienk

2012-01-01

Cancer increases the risk of venous thromboembolism (VTE). Here, we investigated the contribution of microparticle (MP)-dependent procoagulant activity to the prothrombotic state in these patients. In 43 cancer patients without VIE at study entry and 22 healthy volunteers, markers of in vivo and

When Clusters become Networks

NARCIS (Netherlands)

S.M.W. Phlippen (Sandra); G.A. van der Knaap (Bert)

2007-01-01

textabstractPolicy makers spend large amounts of public resources on the foundation of science parks and other forms of geographically clustered business activities, in order to stimulate regional innovation. Underlying the relation between clusters and innovation is the assumption that co-located

Gauging NOTCH1 Activation in Cancer Using Immunohistochemistry.

Directory of Open Access Journals (Sweden)

Michael J Kluk

Full Text Available Fixed, paraffin-embedded (FPE tissues are a potentially rich resource for studying the role of NOTCH1 in cancer and other pathologies, but tests that reliably detect activated NOTCH1 (NICD1 in FPE samples have been lacking. Here, we bridge this gap by developing an immunohistochemical (IHC stain that detects a neoepitope created by the proteolytic cleavage event that activates NOTCH1. Following validation using xenografted cancers and normal tissues with known patterns of NOTCH1 activation, we applied this test to tumors linked to dysregulated Notch signaling by mutational studies. As expected, frequent NICD1 staining was observed in T lymphoblastic leukemia/lymphoma, a tumor in which activating NOTCH1 mutations are common. However, when IHC was used to gauge NOTCH1 activation in other human cancers, several unexpected findings emerged. Among B cell tumors, NICD1 staining was much more frequent in chronic lymphocytic leukemia than would be predicted based on the frequency of NOTCH1 mutations, while mantle cell lymphoma and diffuse large B cell lymphoma showed no evidence of NOTCH1 activation. NICD1 was also detected in 38% of peripheral T cell lymphomas. Of interest, NICD1 staining in chronic lymphocytic leukemia cells and in angioimmunoblastic lymphoma was consistently more pronounced in lymph nodes than in surrounding soft tissues, implicating factors in the nodal microenvironment in NOTCH1 activation in these diseases. Among carcinomas, diffuse strong NICD1 staining was observed in 3.8% of cases of triple negative breast cancer (3 of 78 tumors, but was absent from 151 non-small cell lung carcinomas and 147 ovarian carcinomas. Frequent staining of normal endothelium was also observed; in line with this observation, strong NICD1 staining was also seen in 77% of angiosarcomas. These findings complement insights from genomic sequencing studies and suggest that IHC staining is a valuable experimental tool that may be useful in selection of

Cardiovascular Disease and Cancer: Student Awareness Activities.

Science.gov (United States)

Meyer, James H., Comp.

Awareness activities pertaining to cancer and cardiovascular disease are presented as a supplement for high school science classes. The exercises can be used to enrich units of study dealing with the circulatory system, the cell, or human diseases. Eight activities deal with the following topics: (1) cardiovascular disease risk factors; (2)…

The smart cluster method. Adaptive earthquake cluster identification and analysis in strong seismic regions

Science.gov (United States)

Schaefer, Andreas M.; Daniell, James E.; Wenzel, Friedemann

2017-07-01

Earthquake clustering is an essential part of almost any statistical analysis of spatial and temporal properties of seismic activity. The nature of earthquake clusters and subsequent declustering of earthquake catalogues plays a crucial role in determining the magnitude-dependent earthquake return period and its respective spatial variation for probabilistic seismic hazard assessment. This study introduces the Smart Cluster Method (SCM), a new methodology to identify earthquake clusters, which uses an adaptive point process for spatio-temporal cluster identification. It utilises the magnitude-dependent spatio-temporal earthquake density to adjust the search properties, subsequently analyses the identified clusters to determine directional variation and adjusts its search space with respect to directional properties. In the case of rapid subsequent ruptures like the 1992 Landers sequence or the 2010-2011 Darfield-Christchurch sequence, a reclassification procedure is applied to disassemble subsequent ruptures using near-field searches, nearest neighbour classification and temporal splitting. The method is capable of identifying and classifying earthquake clusters in space and time. It has been tested and validated using earthquake data from California and New Zealand. A total of more than 1500 clusters have been found in both regions since 1980 with M m i n = 2.0. Utilising the knowledge of cluster classification, the method has been adjusted to provide an earthquake declustering algorithm, which has been compared to existing methods. Its performance is comparable to established methodologies. The analysis of earthquake clustering statistics lead to various new and updated correlation functions, e.g. for ratios between mainshock and strongest aftershock and general aftershock activity metrics.

[Clinical research activity of the French cancer cooperative network: Overview and perspectives].

Science.gov (United States)

Dubois, Claire; Morin, Franck; Moro-Sibilot, Denis; Langlais, Alexandra; Seitz, Jean-François; Girault, Cécile; Salles, Gilles; Haioun, Corinne; Deschaseaux, Pascal; Casassus, Philippe; Mathiot, Claire; Pujade-Lauraine, Éric; Votan, Bénédicte; Louvet, Christophe; Delpeut, Christine; Bardet, Étienne; Vintonenko, Nadejda; Hoang Xuan, Khê; Vo, Maryline; Michon, Jean; Milleron, Bernard

The French Cancer Plan 2014-2019 stresses the importance of strengthening collaboration between all stakeholders involved in the fight against cancer, including cancer cooperative groups and intergroups. This survey aimed to describe the basics characteristics and clinical research activity among the Cancer Cooperative Groups (Groupes coopérateurs en oncologie). The second objective was to identify facilitators and barriers to their research activity. A questionnaire was sent to all the clinicians involved in 2014 as investigators in a clinical trial sponsored by one of the ten members of the Cancer Cooperative Groups network. The questions were related to their profile, research activity and the infrastructure existing within their healthcare center to support clinical research and related compliance activities. In total, 366 investigators responded to our survey. The academic clinical trials sponsored by the Cancer Cooperative Groups represented an important part of the research activity of the investigators in France in 2014. These academic groups contributed to the opening of many research sites throughout all regions in France. Factors associated with a higher participation of investigators (more than 10 patients enrolled in a trial over a year) include the existing support of healthcare professionals (more than 2 clinical research associate (CRA) OR=11.16 [3.82-32.6] compared to none) and the practice of their research activity in a University Hospital Center (CHU) rather than a Hospital Center (CH) (OR=2.15 [1.20-3.83]). This study highlighted factors that can strengthen investigator clinical research activities and subsequently improve patient access to evidence-based new cancer therapies in France. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors

Directory of Open Access Journals (Sweden)

Sara Pizzamiglio

2017-02-01

Full Text Available We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA or reverse-phase protein array (RPPA, were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors. We found that cancerous tissues had higher level of hepcidin than benign lesions (p = 0.012. The univariate analysis of RPPA data highlighted the following seven proteins differentially expressed between non-cancerous and cancerous breast tissue: signal transducer and transcriptional activator 5 (STAT5, signal transducer and activator of transcription 3 (STAT3, bone morphogenetic protein 6 (BMP6, cluster of differentiation 74 (CD74, transferrin receptor (TFRC, inhibin alpha (INHA, and STAT5_pY694. These findings were confirmed for STAT5, STAT3, BMP6, CD74 and INHA when adjusting for age. The multivariate statistical analysis indicated an iron-related 10-protein panel effective in separating non-cancerous from cancerous lesions including STAT5, STAT5_pY694, myeloid differentiation factor 88 (MYD88, CD74, iron exporter ferroportin (FPN, high mobility group box 1 (HMGB1, STAT3_pS727, TFRC, ferritin heavy chain (FTH, and ferritin light chain (FTL. Our results showed an association between some iron-related proteins and the type of tumor tissue, which may provide insight in strategies for using iron chelators to treat breast cancer.

PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer

DEFF Research Database (Denmark)

Koefoed Petersen, Rasmus; Benzon Larsen, Signe; Jensen, Ditte Marie

2012-01-01

Alcohol is a risk factor for postmenopausal breast cancer. One of several proposed mechanisms is that alcohol-related breast cancer is caused by increased sex hormone levels. PPARγ inhibits aromatase transcription in breast adipocytes. We reproduced previously found allele-specific effects...... of the wildtype Pro-allele of PPARG Pro12Ala in alcohol related breast cancer. In transiently transfected cells, transcriptional activation by PPARγ and the PPARγ-PGC-1α complex was inhibited by ethanol. PPARγ 12Ala-mediated transcription activation was not enhanced by PGC-1α, resulting in allele......-specific transcription activation by the PPARγ 12Pro-PGC-1α complex. Our results suggest that PPARγ and PGC-1α activity is an important determinant of alcohol related breast cancer....

Radio investigations of clusters of galaxies

International Nuclear Information System (INIS)

Valentijn, E.A.

1978-01-01

This thesis contains a number of papers of the series entitled, A Westerbork Survey of Rich Clusters of Galaxies. The primary aim was to study the radio characteristics of cluster galaxies and especially the question whether their ''radio-activity'' is influenced by their location inside a cluster. It is enquired whether the presence of an intra-cluster medium (ICM), or the typical cluster evolution or cluster dynamical processes can give rise to radio-observable effects on the behaviour of cluster galaxies. 610 MHz WSRT observations of the Coma cluster (and radio observations of the Hercules supercluster) are presented. Extended radio sources in Abell clusters are then described. (Auth.)

Clustering-based approaches to SAGE data mining

Directory of Open Access Journals (Sweden)

Wang Haiying

2008-07-01

Full Text Available Abstract Serial analysis of gene expression (SAGE is one of the most powerful tools for global gene expression profiling. It has led to several biological discoveries and biomedical applications, such as the prediction of new gene functions and the identification of biomarkers in human cancer research. Clustering techniques have become fundamental approaches in these applications. This paper reviews relevant clustering techniques specifically designed for this type of data. It places an emphasis on current limitations and opportunities in this area for supporting biologically-meaningful data mining and visualisation.

Troglitazone suppresses telomerase activity independently of PPARγ in estrogen-receptor negative breast cancer cells

International Nuclear Information System (INIS)

Rashid-Kolvear, Fariborz; Taboski, Michael AS; Nguyen, Johnny; Wang, Dong-Yu; Harrington, Lea A; Done, Susan J

2010-01-01

Breast cancer is one the highest causes of female cancer death worldwide. Many standard chemotherapeutic agents currently used to treat breast cancer are relatively non-specific and act on all rapidly dividing cells. In recent years, more specific targeted therapies have been introduced. It is known that telomerase is active in over 90% of breast cancer tumors but inactive in adjacent normal tissues. The prevalence of active telomerase in breast cancer patients makes telomerase an attractive therapeutic target. Recent evidence suggests that telomerase activity can be suppressed by peroxisome proliferator activated receptor gamma (PPARγ). However, its effect on telomerase regulation in breast cancer has not been investigated. In this study, we investigated the effect of the PPARγ ligand, troglitazone, on telomerase activity in the MDA-MB-231 breast cancer cell line. Real time RT-PCR and telomerase activity assays were used to evaluate the effect of troglitazone. MDA-MB-231 cells had PPARγ expression silenced using shRNA interference. We demonstrated that troglitazone reduced the mRNA expression of hTERT and telomerase activity in the MDA-MB-231 breast cancer cell line. Troglitazone reduced telomerase activity even in the absence of PPARγ. In agreement with this result, we found no correlation between PPARγ and hTERT mRNA transcript levels in breast cancer patients. Statistical significance was determined using Pearson correlation and the paired Student's t test. To our knowledge, this is the first time that the effect of troglitazone on telomerase activity in breast cancer cells has been investigated. Our data suggest that troglitazone may be used as an anti-telomerase agent; however, the mechanism underlying this inhibitory effect remains to be determined

Cytotoxic activities of amentoflavone against human breast and cervical cancers are mediated by increasing of PTEN expression levels due to peroxisomes proliferate-activated receptor {gamma} activation

Energy Technology Data Exchange (ETDEWEB)

Lee, Eunjung; Shin, Soyoung; Lee, Jeeyoung; Lee, So Jung; Kim, Jinkyoung; Yoon, Doyoung; Kim, Yangmee [Konkuk Univ., Seoul (Korea, Republic of); Woo, Eunrhan [Chosun Univ., Gwangju (Korea, Republic of)

2012-07-15

Human peroxisomes proliferate-activated receptor gamma (hPPAR{gamma}) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. Previously, we verified that amentoflavone is an activator of hPPAR{gamma} and probed the molecular basis of its action. In this study, we investigated the mechanism of action of amentoflavone in cancer cells and demonstrated that amentoflavone showed strong cytotoxicity against MCF-7 and HeLa cancer cell lines. We showed that hPPAR{gamma} expression in MCF-7 and HeLa cells is specifically stimulated by amentoflavone, and suggested that amentoflavone-induced cytotoxic activities are mediated by activation of hPPAR{gamma} in these two cancer cell lines. Moreover, amentoflavone increased PTEN levels in these two cancer cell lines, indicating that the cytotoxic activities of amentoflavone are mediated by increasing of PTEN expression levels due to hPPAR{gamma} activation.

The impact of cancer and its treatment on physical activity levels and quality of life among young Hong Kong Chinese cancer patients.

Science.gov (United States)

Lam, Katherine K W; Li, William H C; Chiu, S Y; Chan, Godfrey C F

2016-04-01

Despite the evidence that regular physical activity can have beneficial effects on the physical and psychological well-being of cancer patients, a review of the literature reveals that a majority of young cancer patients fail to attain the same levels of physical activity that they had before contracting the disease. This study is to examine the impact of cancer and its treatment on the physical activity levels and quality of life of young Hong Kong Chinese cancer patients. A cross-sectional study was conducted, with 76 young cancer patients admitted for treatment to a pediatric oncology unit, and another similar age group of 148 healthy counterparts from the two integrated child and youth service centers were invited to join the study. The study found that the current physical activity levels of young cancer patients were markedly reduced when compared with their pre-cancer situation. Moreover, they were significantly less active in performing physical exercise, and reported lower levels of self-efficacy and quality of life than their healthy counterparts. The results of the hierarchical multiple regression analysis showed that physical activity is an important indicator of quality of life among young cancer patients. The results provide further evidence that cancer and its treatment have negative effects on physical and psychological well-being and quality of life among young cancer patients. There is an imperative need for healthcare professionals to promote the adoption of regular physical activity among such patients, even during the treatment itself. Copyright © 2016 Elsevier Ltd. All rights reserved.

NFκB-mediated activation of the cellular FUT3, 5 and 6 gene cluster by herpes simplex virus type 1.

Science.gov (United States)

Nordén, Rickard; Samuelsson, Ebba; Nyström, Kristina

2017-11-01

Herpes simplex virus type 1 has the ability to induce expression of a human gene cluster located on chromosome 19 upon infection. This gene cluster contains three fucosyltransferases (encoded by FUT3, FUT5 and FUT6) with the ability to add a fucose to an N-acetylglucosamine residue. Little is known regarding the transcriptional activation of these three genes in human cells. Intriguingly, herpes simplex virus type 1 activates all three genes simultaneously during infection, a situation not observed in uninfected tissue, pointing towards a virus specific mechanism for transcriptional activation. The aim of this study was to define the underlying mechanism for the herpes simplex virus type 1 activation of FUT3, FUT5 and FUT6 transcription. The transcriptional activation of the FUT-gene cluster on chromosome 19 in fibroblasts was specific, not involving adjacent genes. Moreover, inhibition of NFκB signaling through panepoxydone treatment significantly decreased the induction of FUT3, FUT5 and FUT6 transcriptional activation, as did siRNA targeting of p65, in herpes simplex virus type 1 infected fibroblasts. NFκB and p65 signaling appears to play an important role in the regulation of FUT3, FUT5 and FUT6 transcriptional activation by herpes simplex virus type 1 although additional, unidentified, viral factors might account for part of the mechanism as direct interferon mediated stimulation of NFκB was not sufficient to induce the fucosyltransferase encoding gene cluster in uninfected cells. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling.

Science.gov (United States)

Shrestha, Y; Schafer, E J; Boehm, J S; Thomas, S R; He, F; Du, J; Wang, S; Barretina, J; Weir, B A; Zhao, J J; Polyak, K; Golub, T R; Beroukhim, R; Hahn, W C

2012-07-19

Activating mutations in the RAS family or BRAF frequently occur in many types of human cancers but are rarely detected in breast tumors. However, activation of the RAS-RAF-MEK-ERK MAPK pathway is commonly observed in human breast cancers, suggesting that other genetic alterations lead to activation of this signaling pathway. To identify breast cancer oncogenes that activate the MAPK pathway, we screened a library of human kinases for their ability to induce anchorage-independent growth in a derivative of immortalized human mammary epithelial cells (HMLE). We identified p21-activated kinase 1 (PAK1) as a kinase that permitted HMLE cells to form anchorage-independent colonies. PAK1 is amplified in several human cancer types, including 30--33% of breast tumor samples and cancer cell lines. The kinase activity of PAK1 is necessary for PAK1-induced transformation. Moreover, we show that PAK1 simultaneously activates MAPK and MET signaling; the latter via inhibition of merlin. Disruption of these activities inhibits PAK1-driven anchorage-independent growth. These observations establish PAK1 amplification as an alternative mechanism for MAPK activation in human breast cancer and credential PAK1 as a breast cancer oncogene that coordinately regulates multiple signaling pathways, the cooperation of which leads to malignant transformation.

Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

Energy Technology Data Exchange (ETDEWEB)

Jeong, Jin Boo [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States); Lee, Seong-Ho, E-mail: slee2000@umd.edu [Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742 (United States)

2013-01-04

Highlights: Black-Right-Pointing-Pointer Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. Black-Right-Pointing-Pointer PCA enhanced transcriptional downregulation of cyclin D1 gene. Black-Right-Pointing-Pointer PCA suppressed HDAC2 expression and activity. Black-Right-Pointing-Pointer These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.

Protocatechualdehyde possesses anti-cancer activity through downregulating cyclin D1 and HDAC2 in human colorectal cancer cells

International Nuclear Information System (INIS)

Jeong, Jin Boo; Lee, Seong-Ho

2013-01-01

Highlights: ► Protocatechualdehyde (PCA) suppressed cell proliferation and induced apoptosis in human colorectal cancer cells. ► PCA enhanced transcriptional downregulation of cyclin D1 gene. ► PCA suppressed HDAC2 expression and activity. ► These findings suggest that anti-cancer activity of PCA may be mediated by reducing HDAC2-derived cyclin D1 expression. -- Abstract: Protocatechualdehyde (PCA) is a naturally occurring polyphenol found in barley, green cavendish bananas, and grapevine leaves. Although a few studies reported growth-inhibitory activity of PCA in breast and leukemia cancer cells, the underlying mechanisms are still poorly understood. Thus, we performed in vitro study to investigate if treatment of PCA affects cell proliferation and apoptosis in human colorectal cancer cells and define potential mechanisms by which PCA mediates growth arrest and apoptosis of cancer cells. Exposure of PCA to human colorectal cancer cells (HCT116 and SW480 cells) suppressed cell growth and induced apoptosis in dose-dependent manner. PCA decreased cyclin D1 expression in protein and mRNA level and suppressed luciferase activity of cyclin D1 promoter, indicating transcriptional downregulation of cyclin D1 gene by PCA. We also observed that PCA treatment attenuated enzyme activity of histone deacetylase (HDAC) and reduced expression of HDAC2, but not HDAC1. These findings suggest that cell growth inhibition and apoptosis by PCA may be a result of HDAC2-mediated cyclin D1 suppression.

Association of Physical Activity by Type and Intensity With Digestive System Cancer Risk.

Science.gov (United States)

Keum, NaNa; Bao, Ying; Smith-Warner, Stephanie A; Orav, John; Wu, Kana; Fuchs, Charles S; Giovannucci, Edward L

2016-09-01

Accumulating evidence indicates that common carcinogenic pathways may underlie digestive system cancers. Physical activity may influence these pathways. Yet, to our knowledge, no previous study has evaluated the role of physical activity in overall digestive system cancer risk. To examine the association between physical activity and digestive system cancer risk, accounting for amount, type (aerobic vs resistance), and intensity of physical activity. A prospective cohort study followed 43 479 men from the Health Professionals Follow-up Study from 1986 to 2012. At enrollment, the eligible participants were 40 years or older, were free of cancer, and reported physical activity. Follow-up rates exceeded 90% in each 2-year cycle. The amount of total physical activity expressed in metabolic equivalent of task (MET)-hours/week. Incident cancer of the digestive system encompassing the digestive tract (mouth, throat, esophagus, stomach, small intestine, and colorectum) and digestive accessory organs (pancreas, gallbladder, and liver). Over 686 924 person-years, we documented 1370 incident digestive system cancers. Higher levels of physical activity were associated with lower digestive system cancer risk (hazard ratio [HR], 0.74 for ≥63.0 vs ≤8.9 MET-hours/week; 95% CI, 0.59-0.93; P value for trend = .003). The inverse association was more evident with digestive tract cancers (HR, 0.66 for ≥63.0 vs ≤8.9 MET-hours/week; 95% CI, 0.51-0.87) than with digestive accessary organ cancers. Aerobic exercise was particularly beneficial against digestive system cancers, with the optimal benefit observed at approximately 30 MET-hours/week (HR, 0.68; 95% CI, 0.56-0.83; P value for nonlinearity = .02). Moreover, as long as the same level of MET-hour score was achieved from aerobic exercise, the magnitude of risk reduction was similar regardless of intensity of aerobic exercise. Physical activity, as indicated by MET-hours/week, was inversely associated with the risk of