Postdiagnosis social networks and breast cancer mortality in the After Breast Cancer Pooling Project.

Science.gov (United States)

Kroenke, Candyce H; Michael, Yvonne L; Poole, Elizabeth M; Kwan, Marilyn L; Nechuta, Sarah; Leas, Eric; Caan, Bette J; Pierce, John; Shu, Xiao-Ou; Zheng, Ying; Chen, Wendy Y

2017-04-01

Large social networks have been associated with better overall survival, though not consistently with breast cancer (BC)-specific outcomes. This study evaluated associations of postdiagnosis social networks and BC outcomes in a large cohort. Women from the After Breast Cancer Pooling Project (n = 9267) provided data on social networks within approximately 2 years of their diagnosis. A social network index was derived from information about the presence of a spouse/partner, religious ties, community ties, friendship ties, and numbers of living first-degree relatives. Cox models were used to evaluate associations, and a meta-analysis was used to determine whether effect estimates differed by cohort. Stratification by demographic, social, tumor, and treatment factors was performed. There were 1448 recurrences and 1521 deaths (990 due to BC). Associations were similar in 3 of 4 cohorts. After covariate adjustments, socially isolated women (small networks) had higher risks of recurrence (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.15-1.77), BC-specific mortality (HR, 1.64; 95% CI, 1.33-2.03), and total mortality (HR, 1.69; 95% CI, 1.43-1.99) than socially integrated women; associations were stronger in those with stage I/II cancer. In the fourth cohort, there were no significant associations with BC-specific outcomes. A lack of a spouse/partner (P = .02) and community ties (P = .04) predicted higher BC-specific mortality in older white women but not in other women. However, a lack of relatives (P = .02) and friendship ties (P = .01) predicted higher BC-specific mortality in nonwhite women only. In a large pooled cohort, larger social networks were associated with better BC-specific and overall survival. Clinicians should assess social network information as a marker of prognosis because critical supports may differ with sociodemographic factors. Cancer 2017;123:1228-1237. © 2016 American Cancer Society. © 2016 American Cancer Society.

Network of microRNAs-mRNAs Interactions in Pancreatic Cancer

Science.gov (United States)

Naderi, Elnaz; Mostafaei, Mehdi; Pourshams, Akram

2014-01-01

Background. MicroRNAs are small RNA molecules that regulate the expression of certain genes through interaction with mRNA targets and are mainly involved in human cancer. This study was conducted to make the network of miRNAs-mRNAs interactions in pancreatic cancer as the fourth leading cause of cancer death. Methods. 56 miRNAs that were exclusively expressed and 1176 genes that were downregulated or silenced in pancreas cancer were extracted from beforehand investigations. MiRNA–mRNA interactions data analysis and related networks were explored using MAGIA tool and Cytoscape 3 software. Functional annotations of candidate genes in pancreatic cancer were identified by DAVID annotation tool. Results. This network is made of 217 nodes for mRNA, 15 nodes for miRNA, and 241 edges that show 241 regulations between 15 miRNAs and 217 target genes. The miR-24 was the most significantly powerful miRNA that regulated series of important genes. ACVR2B, GFRA1, and MTHFR were significant target genes were that downregulated. Conclusion. Although the collected previous data seems to be a treasure trove, there was no study simultaneous to analysis of miRNAs and mRNAs interaction. Network of miRNA-mRNA interactions will help to corroborate experimental remarks and could be used to refine miRNA target predictions for developing new therapeutic approaches. PMID:24895587

Network of microRNAs-mRNAs Interactions in Pancreatic Cancer

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Elnaz Naderi

2014-01-01

Full Text Available Background. MicroRNAs are small RNA molecules that regulate the expression of certain genes through interaction with mRNA targets and are mainly involved in human cancer. This study was conducted to make the network of miRNAs-mRNAs interactions in pancreatic cancer as the fourth leading cause of cancer death. Methods. 56 miRNAs that were exclusively expressed and 1176 genes that were downregulated or silenced in pancreas cancer were extracted from beforehand investigations. MiRNA–mRNA interactions data analysis and related networks were explored using MAGIA tool and Cytoscape 3 software. Functional annotations of candidate genes in pancreatic cancer were identified by DAVID annotation tool. Results. This network is made of 217 nodes for mRNA, 15 nodes for miRNA, and 241 edges that show 241 regulations between 15 miRNAs and 217 target genes. The miR-24 was the most significantly powerful miRNA that regulated series of important genes. ACVR2B, GFRA1, and MTHFR were significant target genes were that downregulated. Conclusion. Although the collected previous data seems to be a treasure trove, there was no study simultaneous to analysis of miRNAs and mRNAs interaction. Network of miRNA-mRNA interactions will help to corroborate experimental remarks and could be used to refine miRNA target predictions for developing new therapeutic approaches.

Social Network Structures of Breast Cancer Patients and the Contributing Role of Patient Navigators.

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Gunn, Christine M; Parker, Victoria A; Bak, Sharon M; Ko, Naomi; Nelson, Kerrie P; Battaglia, Tracy A

2017-08-01

Minority women in the U.S. continue to experience inferior breast cancer outcomes compared with white women, in part due to delays in care delivery. Emerging cancer care delivery models like patient navigation focus on social barriers, but evidence demonstrating how these models increase social capital is lacking. This pilot study describes the social networks of newly diagnosed breast cancer patients and explores the contributing role of patient navigators. Twenty-five women completed a one hour interview about their social networks related to cancer care support. Network metrics identified important structural attributes and influential individuals. Bivariate associations between network metrics, type of network, and whether the network included a navigator were measured. Secondary analyses explored associations between network structures and clinical outcomes. We identified three types of networks: kin-based, role and/or affect-based, or heterogeneous. Network metrics did not vary significantly by network type. There was a low prevalence of navigators included in the support networks (25%). Network density scores were significantly higher in those networks without a navigator. Network metrics were not predictive of clinical outcomes in multivariate models. Patient navigators were not frequently included in support networks, but provided distinctive types of support. If navigators can identify patients with poorly integrated (less dense) social networks, or who have unmet tangible support needs, the intensity of navigation services could be tailored. Services and systems that address gaps and variations in patient social networks should be explored for their potential to reduce cancer health disparities. This study used a new method to identify the breadth and strength of social support following a diagnosis of breast cancer, especially examining the role of patient navigators in providing support. While navigators were only included in one quarter of patient

Navigating cancer network attractors for tumor-specific therapy

DEFF Research Database (Denmark)

Creixell, Pau; Schoof, Erwin; Erler, Janine Terra

2012-01-01

understanding of the processes by which genetic lesions perturb these networks and lead to disease phenotypes. Network biology will help circumvent fundamental obstacles in cancer treatment, such as drug resistance and metastasis, empowering personalized and tumor-specific cancer therapies....

Machine Learning-Assisted Network Inference Approach to Identify a New Class of Genes that Coordinate the Functionality of Cancer Networks.

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Ghanat Bari, Mehrab; Ung, Choong Yong; Zhang, Cheng; Zhu, Shizhen; Li, Hu

2017-08-01

Emerging evidence indicates the existence of a new class of cancer genes that act as "signal linkers" coordinating oncogenic signals between mutated and differentially expressed genes. While frequently mutated oncogenes and differentially expressed genes, which we term Class I cancer genes, are readily detected by most analytical tools, the new class of cancer-related genes, i.e., Class II, escape detection because they are neither mutated nor differentially expressed. Given this hypothesis, we developed a Machine Learning-Assisted Network Inference (MALANI) algorithm, which assesses all genes regardless of expression or mutational status in the context of cancer etiology. We used 8807 expression arrays, corresponding to 9 cancer types, to build more than 2 × 10 8 Support Vector Machine (SVM) models for reconstructing a cancer network. We found that ~3% of ~19,000 not differentially expressed genes are Class II cancer gene candidates. Some Class II genes that we found, such as SLC19A1 and ATAD3B, have been recently reported to associate with cancer outcomes. To our knowledge, this is the first study that utilizes both machine learning and network biology approaches to uncover Class II cancer genes in coordinating functionality in cancer networks and will illuminate our understanding of how genes are modulated in a tissue-specific network contribute to tumorigenesis and therapy development.

Fox Chase Network: Fox Chase Cancer Center's community hospital affiliation program.

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Higman, S A; McKay, F J; Engstrom, P F; O'Grady, M A; Young, R C

2000-01-01

Fox Chase Cancer Center developed a format for affiliation with community providers in 1986. Fox Chase Network was formed to establish hospital-based community cancer centers to increase access to patients involved in clinical research. Under this program, the Fox Chase Network now contributes 500 patients per year to prevention and clinical research studies. As relationships with community providers form, patient referrals have increased at Fox Chase Cancer Center and for each Fox Chase Network member. A dedicated staff is required to operate the central office on a day-to-day basis as well as at each affiliate. We have found this to be a critical element in each program's success. New challenges in the cancer business-increasing volumes with declining revenue-have caused us to reconfigure the services offered to affiliates, while maintaining true to our mission: to reduce the burden of human cancer.

Using Social Network Analysis to Evaluate Community Capacity Building of a Regional Community Cancer Network

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Luque, John; Tyson, Dinorah Martinez; Lee, Ji-Hyun; Gwede, Clement; Vadaparampil, Susan; Noel-Thomas, Shalewa; Meade, Cathy

2010-01-01

The Tampa Bay Community Cancer Network (TBCCN) is one of 25 Community Network Programs funded by the National Cancer Institute's (NCI's) Center to Reduce Cancer Health Disparities with the objectives to create a collaborative infrastructure of academic and community based organizations and to develop effective and sustainable interventions to…

Network perturbation by recurrent regulatory variants in cancer.

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Kiwon Jang

2017-03-01

Full Text Available Cancer driving genes have been identified as recurrently affected by variants that alter protein-coding sequences. However, a majority of cancer variants arise in noncoding regions, and some of them are thought to play a critical role through transcriptional perturbation. Here we identified putative transcriptional driver genes based on combinatorial variant recurrence in cis-regulatory regions. The identified genes showed high connectivity in the cancer type-specific transcription regulatory network, with high outdegree and many downstream genes, highlighting their causative role during tumorigenesis. In the protein interactome, the identified transcriptional drivers were not as highly connected as coding driver genes but appeared to form a network module centered on the coding drivers. The coding and regulatory variants associated via these interactions between the coding and transcriptional drivers showed exclusive and complementary occurrence patterns across tumor samples. Transcriptional cancer drivers may act through an extensive perturbation of the regulatory network and by altering protein network modules through interactions with coding driver genes.

Lessons Learned from the Young Breast Cancer Survivorship Network.

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Gisiger-Camata, Silvia; Nolan, Timiya S; Vo, Jacqueline B; Bail, Jennifer R; Lewis, Kayla A; Meneses, Karen

2017-11-30

The Young Breast Cancer Survivors Network (Network) is an academic and community-based partnership dedicated to education, support, and networking. The Network used a multi-pronged approach via monthly support and networking, annual education seminars, website networking, and individual survivor consultation. Formative and summative evaluations were conducted using group survey and individual survivor interviews for monthly gatherings, annual education meetings, and individual consultation. Google Analytics was applied to evaluate website use. The Network began with 4 initial partnerships and grew to 38 in the period from 2011 to 2017. During this 5-year period, 5 annual meetings (598 attendees), 23 support and networking meetings (373), and 115 individual survivor consultations were conducted. The Network website had nearly 12,000 individual users and more than 25,000 page views. Lessons learned include active community engagement, survivor empowerment, capacity building, social media outreach, and network sustainability. The 5-year experiences with the Network demonstrated that a regional program dedicated to the education, support, networking, and needs of young breast cancer survivors and their families can become a vital part of cancer survivorship services in a community. Strong community support, engagement, and encouragement were vital components to sustain the program.

Identification of Gene Biomarkers for Distinguishing Small-Cell Lung Cancer from Non-Small-Cell Lung Cancer Using a Network-Based Approach

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Fei Long

2015-01-01

Full Text Available Lung cancer consists of two main subtypes: small-cell lung cancer (SCLC and non-small-cell lung cancer (NSCLC that are classified according to their physiological phenotypes. In this study, we have developed a network-based approach to identify molecular biomarkers that can distinguish SCLC from NSCLC. By identifying positive and negative coexpression gene pairs in normal lung tissues, SCLC, or NSCLC samples and using functional association information from the STRING network, we first construct a lung cancer-specific gene association network. From the network, we obtain gene modules in which genes are highly functionally associated with each other and are either positively or negatively coexpressed in the three conditions. Then, we identify gene modules that not only are differentially expressed between cancer and normal samples, but also show distinctive expression patterns between SCLC and NSCLC. Finally, we select genes inside those modules with discriminating coexpression patterns between the two lung cancer subtypes and predict them as candidate biomarkers that are of diagnostic use.

Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.

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Kesler, Shelli R; Watson, Christa L; Blayney, Douglas W

2015-08-01

Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes. Copyright © 2015 Elsevier Inc. All rights reserved.

Legacy of the Pacific Islander cancer control network.

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Hubbell, F Allan; Luce, Pat H; Afeaki, William P; Cruz, Lee Ann C; McMullin, Juliet M; Mummert, Angelina; Pouesi, June; Reyes, Maria Lourdes; Taumoepeau, Leafa Tuita; Tu'ufuli, Galeai Moali'itele; Wenzel, Lari

2006-10-15

The groundwork for the Pacific Islander cancer control network (PICCN) began in the early 1990s with a study of the cancer control needs of American Samoans. The necessity for similar studies among other Pacific Islander populations led to the development of PICCN. The project's principal objectives were to increase cancer awareness and to enhance cancer control research among American Samoans, Tongans, and Chamorros. PICCN was organized around a steering committee and 6 community advisory boards, 2 from each of the targeted populations. Membership included community leaders, cancer control experts, and various academic and technical organizations involved with cancer control. Through this infrastructure, the investigators developed new culturally sensitive cancer education materials and distributed them in a culturally appropriate manner. They also initiated a cancer control research training program, educated Pacific Islander students in this field, and conducted pilot research projects. PICCN conducted nearly 200 cancer awareness activities in its 6 study sites and developed cancer educational materials on prostate, colorectal, lung, breast, and cervical cancer and tobacco control in the Samoan, Tongan, and Chamorro languages. PICCN trained 9 students who conducted 7 pilot research projects designed to answer important questions regarding the cancer control needs of Pacific Islanders and to inform interventions targeting those needs. The legacy of PICCN lies in its advancement of improving cancer control among Pacific Islanders and setting the stage for interventions that will help to eliminate cancer-related health disparities. Cancer 2006. (c) 2006 American Cancer Society.

Increased signaling entropy in cancer requires the scale-free property of protein interaction networks

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Teschendorff, Andrew E.; Banerji, Christopher R. S.; Severini, Simone; Kuehn, Reimer; Sollich, Peter

2015-01-01

One of the key characteristics of cancer cells is an increased phenotypic plasticity, driven by underlying genetic and epigenetic perturbations. However, at a systems-level it is unclear how these perturbations give rise to the observed increased plasticity. Elucidating such systems-level principles is key for an improved understanding of cancer. Recently, it has been shown that signaling entropy, an overall measure of signaling pathway promiscuity, and computable from integrating a sample's gene expression profile with a protein interaction network, correlates with phenotypic plasticity and is increased in cancer compared to normal tissue. Here we develop a computational framework for studying the effects of network perturbations on signaling entropy. We demonstrate that the increased signaling entropy of cancer is driven by two factors: (i) the scale-free (or near scale-free) topology of the interaction network, and (ii) a subtle positive correlation between differential gene expression and node connectivity. Indeed, we show that if protein interaction networks were random graphs, described by Poisson degree distributions, that cancer would generally not exhibit an increased signaling entropy. In summary, this work exposes a deep connection between cancer, signaling entropy and interaction network topology. PMID:25919796

Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells.

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Chang, Hsin-Yi; Li, Ming-Hua; Huang, Tsui-Chin; Hsu, Chia-Lang; Tsai, Shang-Ru; Lee, Si-Chen; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

2015-02-06

Breast cancer is one of the leading cancer-related causes of death worldwide. Treatment of triple-negative breast cancer (TNBC) is complex and challenging, especially when metastasis has developed. In this study, we applied infrared radiation as an alternative approach for the treatment of TNBC. We used middle infrared (MIR) with a wavelength range of 3-5 μm to irradiate breast cancer cells. MIR significantly inhibited cell proliferation in several breast cancer cells but did not affect the growth of normal breast epithelial cells. We performed iTRAQ-coupled LC-MS/MS analysis to investigate the MIR-triggered molecular mechanisms in breast cancer cells. A total of 1749 proteins were identified, quantified, and subjected to functional enrichment analysis. From the constructed functionally enriched network, we confirmed that MIR caused G2/M cell cycle arrest, remodeled the microtubule network to an astral pole arrangement, altered the actin filament formation and focal adhesion molecule localization, and reduced cell migration activity and invasion ability. Our results reveal the coordinative effects of MIR-regulated physiological responses in concentrated networks, demonstrating the potential implementation of infrared radiation in breast cancer therapy.

Endogenous Molecular-Cellular Network Cancer Theory: A Systems Biology Approach.

Science.gov (United States)

Wang, Gaowei; Yuan, Ruoshi; Zhu, Xiaomei; Ao, Ping

2018-01-01

In light of ever apparent limitation of the current dominant cancer mutation theory, a quantitative hypothesis for cancer genesis and progression, endogenous molecular-cellular network hypothesis has been proposed from the systems biology perspective, now for more than 10 years. It was intended to include both the genetic and epigenetic causes to understand cancer. Its development enters the stage of meaningful interaction with experimental and clinical data and the limitation of the traditional cancer mutation theory becomes more evident. Under this endogenous network hypothesis, we established a core working network of hepatocellular carcinoma (HCC) according to the hypothesis and quantified the working network by a nonlinear dynamical system. We showed that the two stable states of the working network reproduce the main known features of normal liver and HCC at both the modular and molecular levels. Using endogenous network hypothesis and validated working network, we explored genetic mutation pattern in cancer and potential strategies to cure or relieve HCC from a totally new perspective. Patterns of genetic mutations have been traditionally analyzed by posteriori statistical association approaches in light of traditional cancer mutation theory. One may wonder the possibility of a priori determination of any mutation regularity. Here, we found that based on the endogenous network theory the features of genetic mutations in cancers may be predicted without any prior knowledge of mutation propensities. Normal hepatocyte and cancerous hepatocyte stable states, specified by distinct patterns of expressions or activities of proteins in the network, provide means to directly identify a set of most probable genetic mutations and their effects in HCC. As the key proteins and main interactions in the network are conserved through cell types in an organism, similar mutational features may also be found in other cancers. This analysis yielded straightforward and testable

Comparison of Back propagation neural network and Back propagation neural network Based Particle Swarm intelligence in Diagnostic Breast Cancer

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Farahnaz SADOUGHI

2014-03-01

Full Text Available Breast cancer is the most commonly diagnosed cancer and the most common cause of death in women all over the world. Use of computer technology supporting breast cancer diagnosing is now widespread and pervasive across a broad range of medical areas. Early diagnosis of this disease can greatly enhance the chances of long-term survival of breast cancer victims. Artificial Neural Networks (ANN as mainly method play important role in early diagnoses breast cancer. This paper studies Levenberg Marquardet Backpropagation (LMBP neural network and Levenberg Marquardet Backpropagation based Particle Swarm Optimization(LMBP-PSO for the diagnosis of breast cancer. The obtained results show that LMBP and LMBP based PSO system provides higher classification efficiency. But LMBP based PSO needs minimum training and testing time. It helps in developing Medical Decision System (MDS for breast cancer diagnosing. It can also be used as secondary observer in clinical decision making.

Social network characteristics and cervical cancer screening among Quechua women in Andean Peru.

Science.gov (United States)

Luque, John S; Opoku, Samuel; Ferris, Daron G; Guevara Condorhuaman, Wendy S

2016-02-24

Peru has high cervical cancer incidence and mortality rates compared to other Andean countries. Therefore, partnerships between governmental and international organizations have targeted rural areas of Peru to receive cervical cancer screening via outreach campaigns. Previous studies have found a relationship between a person's social networks and cancer screening behaviors. Screening outreach campaigns conducted by the nonprofit organization CerviCusco created an opportunity for a social network study to examine cervical cancer screening history and social network characteristics in a rural indigenous community that participated in these campaigns in 2012 and 2013. The aim of this study was to explore social network characteristics in this community related to receipt of cervical cancer screening following the campaigns. An egocentric social network questionnaire was used to collect cross-sectional network data on community participants. Each survey participant (ego) was asked to name six other women they knew (alters) and identify the nature of their relationship or tie (family, friend, neighbor, other), residential closeness (within 5 km), length of time known, frequency of communication, topics of conversation, and whether they lent money to the person, provided childcare or helped with transportation. In addition, each participant was asked to report the nature of the relationship between all alters identified (e.g., friend, family, or neighbor). Bivariate and multivariate analyses were used to explore the relationship between Pap test receipt at the CerviCusco outreach screening campaigns and social network characteristics. Bivariate results found significant differences in percentage of alter composition for neighbors and family, and for mean number of years known, mean density, and mean degree centrality between women who had received a Pap test (n = 19) compared to those who had not (n = 50) (p's < 0.05). The final logistic regression model was

Construction and analysis of circular RNA molecular regulatory networks in liver cancer.

Science.gov (United States)

Ren, Shuangchun; Xin, Zhuoyuan; Xu, Yinyan; Xu, Jianting; Wang, Guoqing

2017-01-01

Liver cancer is the sixth most prevalent cancer, and the third most frequent cause of cancer-related deaths. Circular RNAs (circRNAs), a kind of special endogenous ncRNAs, have been coming back to the forefront of cancer genomics research. In this study, we used a systems biology approach to construct and analyze the circRNA molecular regulatory networks in the context of liver cancer. We detected a total of 127 differentially expressed circRNAs and 3,235 differentially expressed mRNAs. We selected the top-5 upregulated circRNAs to construct a circRNA-miRNA-mRNA network. We enriched the pathways and gene ontology items and determined their participation in cancer-related pathways such as p53 signaling pathway and pathways involved in angiogenesis and cell cycle. Quantitative real-time PCR was performed to verify the top-five circRNAs. ROC analysis showed circZFR, circFUT8, circIPO11 could significantly distinguish the cancer samples, with an AUC of 0.7069, 0.7575, and 0.7103, respectively. Our results suggest the circRNA-miRNA-mRNA network may help us further understand the molecular mechanisms of tumor progression in liver cancer, and reveal novel biomarkers and therapeutic targets.

Comparative indicators for cancer network management in England: Availability, characteristics and presentation

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Coleman Michel P

2008-02-01

Full Text Available Abstract Background In 2000, the national cancer plan for England created 34 cancer networks, new organisational structures to coordinate services across populations varying between a half and three million people. We investigated the availability of data sets reflecting measures of structure, process and outcome that could be used to support network management. Methods We investigated the properties of national data sets relating to four common cancers – breast, colorectal, lung and prostate. We reviewed the availability and completeness of these data sets, identified leading items within each set and put them into tables of the 34 cancer networks. We also investigated methods of presentation. Results The Acute Hospitals Portfolio and the Cancer Standards Peer Review recorded structural characteristics at hospital and cancer service level. Process measures included Hospital Episode Statistics, recording admissions, and Hospital Waiting-List data. Patient outcome measures included the National Survey of Patient Satisfaction for cancer, and cancer survival, drawn from cancer registration. Data were drawn together to provide an exemplar indicator set a single network, and methods of graphical presentation were considered. Conclusion While not as yet used together in practice, comparative indicators are available within the National Health Service in England for use in performance assessment by cancer networks.

Trends in intensity modulated radiation therapy use for locally advanced rectal cancer at National Comprehensive Cancer Network centers

OpenAIRE

Marsha Reyngold, MD, PhD; Joyce Niland, PhD; Anna ter Veer, MS; Tanios Bekaii-Saab, MD; Lily Lai, MD; Joshua E. Meyer, MD; Steven J. Nurkin, MD, MS; Deborah Schrag, MD, MPH; John M. Skibber, MD, FACS; Al B. Benson, MD; Martin R. Weiser, MD; Christopher H. Crane, MD; Karyn A. Goodman, MD, MS

2018-01-01

Purpose: Intensity modulated radiation therapy (IMRT) has been rapidly incorporated into clinical practice because of its technological advantages over 3-dimensional conformal radiation therapy (CRT). We characterized trends in IMRT utilization in trimodality treatment of locally advanced rectal cancer at National Comprehensive Cancer Network cancer centers between 2005 and 2011. Methods and materials: Using the prospective National Comprehensive Cancer Network Colorectal Cancer Database, ...

Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk.

Science.gov (United States)

Kar, Siddhartha P; Tyrer, Jonathan P; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K H; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V; Bean, Yukie T; Beckmann, Matthias W; Berchuck, Andrew; Bisogna, Maria; Bjørge, Line; Bogdanova, Natalia; Brinton, Louise; Brooks-Wilson, Angela; Butzow, Ralf; Campbell, Ian; Carty, Karen; Chang-Claude, Jenny; Chen, Yian Ann; Chen, Zhihua; Cook, Linda S; Cramer, Daniel; Cunningham, Julie M; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas F; Edwards, Robert P; Ekici, Arif B; Fasching, Peter A; Fridley, Brooke L; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G; Glasspool, Rosalind; Goode, Ellen L; Goodman, Marc T; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A T; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus K; Hosono, Satoyo; Iversen, Edwin S; Jakubowska, Anna; Paul, James; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kjaer, Susanne K; Kelemen, Linda E; Kellar, Melissa; Kelley, Joseph; Kiemeney, Lambertus A; Krakstad, Camilla; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D; Lee, Alice W; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R; McNeish, Iain A; Menon, Usha; Modugno, Francesmary; Moysich, Kirsten B; Narod, Steven A; Nedergaard, Lotte; Ness, Roberta B; Nevanlinna, Heli; Odunsi, Kunle; Olson, Sara H; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M; Permuth-Wey, Jennifer; Phelan, Catherine M; Pike, Malcolm C; Poole, Elizabeth M; Ramus, Susan J; Risch, Harvey A; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H; Rudolph, Anja; Runnebaum, Ingo B; Rzepecka, Iwona K; Salvesen, Helga B; Schildkraut, Joellen M; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C; Sucheston-Campbell, Lara E; Tangen, Ingvild L; Teo, Soo-Hwang; Terry, Kathryn L; Thompson, Pamela J; Timorek, Agnieszka; Tsai, Ya-Yu; Tworoger, Shelley S; van Altena, Anne M; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S; Wicklund, Kristine G; Wilkens, Lynne R; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A; Monteiro, Alvaro N A; Freedman, Matthew L; Gayther, Simon A; Pharoah, Paul D P

2015-10-01

Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations. We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls). Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network. We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development. Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. ©2015 American Association for Cancer Research.

Estimation of the proteomic cancer co-expression sub networks by using association estimators.

Directory of Open Access Journals (Sweden)

Cihat Erdoğan

Full Text Available In this study, the association estimators, which have significant influences on the gene network inference methods and used for determining the molecular interactions, were examined within the co-expression network inference concept. By using the proteomic data from five different cancer types, the hub genes/proteins within the disease-associated gene-gene/protein-protein interaction sub networks were identified. Proteomic data from various cancer types is collected from The Cancer Proteome Atlas (TCPA. Correlation and mutual information (MI based nine association estimators that are commonly used in the literature, were compared in this study. As the gold standard to measure the association estimators' performance, a multi-layer data integration platform on gene-disease associations (DisGeNET and the Molecular Signatures Database (MSigDB was used. Fisher's exact test was used to evaluate the performance of the association estimators by comparing the created co-expression networks with the disease-associated pathways. It was observed that the MI based estimators provided more successful results than the Pearson and Spearman correlation approaches, which are used in the estimation of biological networks in the weighted correlation network analysis (WGCNA package. In correlation-based methods, the best average success rate for five cancer types was 60%, while in MI-based methods the average success ratio was 71% for James-Stein Shrinkage (Shrink and 64% for Schurmann-Grassberger (SG association estimator, respectively. Moreover, the hub genes and the inferred sub networks are presented for the consideration of researchers and experimentalists.

Cooperation among cancer cells as public goods games on Voronoi networks.

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Archetti, Marco

2016-05-07

Cancer cells produce growth factors that diffuse and sustain tumour proliferation, a form of cooperation that can be studied using mathematical models of public goods in the framework of evolutionary game theory. Cell populations, however, form heterogeneous networks that cannot be described by regular lattices or scale-free networks, the types of graphs generally used in the study of cooperation. To describe the dynamics of growth factor production in populations of cancer cells, I study public goods games on Voronoi networks, using a range of non-linear benefits that account for the known properties of growth factors, and different types of diffusion gradients. The results are surprisingly similar to those obtained on regular graphs and different from results on scale-free networks, revealing that network heterogeneity per se does not promote cooperation when public goods diffuse beyond one-step neighbours. The exact shape of the diffusion gradient is not crucial, however, whereas the type of non-linear benefit is an essential determinant of the dynamics. Public goods games on Voronoi networks can shed light on intra-tumour heterogeneity, the evolution of resistance to therapies that target growth factors, and new types of cell therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Breast cancer detection via Hu moment invariant and feedforward neural network

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Zhang, Xiaowei; Yang, Jiquan; Nguyen, Elijah

2018-04-01

One of eight women can get breast cancer during all her life. This study used Hu moment invariant and feedforward neural network to diagnose breast cancer. With the help of K-fold cross validation, we can test the out-of-sample accuracy of our method. Finally, we found that our methods can improve the accuracy of detecting breast cancer and reduce the difficulty of judging.

Randomized Trial of a Social Networking Intervention for Cancer-Related Distress.

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Owen, Jason E; O'Carroll Bantum, Erin; Pagano, Ian S; Stanton, Annette

2017-10-01

Web and mobile technologies appear to hold promise for delivering evidence-informed and evidence-based intervention to cancer survivors and others living with trauma and other psychological concerns. Health-space.net was developed as a comprehensive online social networking and coping skills training program for cancer survivors living with distress. The purpose of this study was to evaluate the effects of a 12-week social networking intervention on distress, depression, anxiety, vigor, and fatigue in cancer survivors reporting high levels of cancer-related distress. We recruited 347 participants from a local cancer registry and internet, and all were randomized to either a 12-week waiting list control group or to immediate access to the intervention. Intervention participants received secure access to the study website, which provided extensive social networking capabilities and coping skills training exercises facilitated by a professional facilitator. Across time, the prevalence of clinically significant depression symptoms declined from 67 to 34 % in both conditions. The health-space.net intervention had greater declines in fatigue than the waitlist control group, but the intervention did not improve outcomes for depression, trauma-related anxiety symptoms, or overall mood disturbance. For those with more severe levels of anxiety at baseline, greater engagement with the intervention was associated with higher levels of symptom reduction over time. The intervention resulted in small but significant effects on fatigue but not other primary or secondary outcomes. Results suggest that this social networking intervention may be most effective for those who have distress that is not associated with high levels of anxiety symptoms or very poor overall psychological functioning. The trial was registered with the ClinicalTrials.gov database ( ClinicalTrials.gov #NCT01976949).

Breast cancer publication network: profile of co-authorship and co-organization.

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Biglu, Mohammad-Hossein; Abotalebi, Parvaneh; Ghavami, Mostafa

2016-01-01

Introduction: Breast cancer is one of the highest reasons of deaths for people in the world. The objective of current study is to analyze and visualize the trend of global scientific activities in the field of breast cancer during a period of 10 years through 2006-2015. Methods: The current study was performed by utilizing the scientometrics analysis and mapping the co-authorship and co-organization networks. The Web of Science Core Collection (WoS-CC)database was used to extract all papers indexed as a topic of breast cancer through 2006 to 2015. Research productivity was measured through analysis several parameters, including: the number and time course of publications, the journal and language of publications, the frequency and type of publications, as well as top 20 active sub-categories together with country contribution. The extracted data were transferred into the Excel charts and plotted as diagrams. The Science of Science (Sci2) and CiteSpace softwares were used as tools for mapping the co-authorship and co-organization networks of the published papers. Results: Analysis of data indicated that the number of publications in the field of breast cancer has linearly increased and correlated with the time-course of the study. The number of publication indexed in WoS-CC in 2015 was two times greater than that of 2006, which reached from 15 229 documents in 2006 to 30 667 documents in 2015. English Language accounted for 98% of total publications as the most dominant language. The vast majority of publications' type was in the form of original journal articles (64.7%). Based on Bradford scatterings law, the journal of "Cancer Research" was the most productive journal among the core journals, while the USA, China, and England were the most prolific countries in the field. The co-organization network indicated the dominant role of Harvard University in the field. Conclusion: The integrity of network indicated that scientists in the field of breast cancer

Social network characteristics and cervical cancer screening among Quechua women in Andean Peru

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John S. Luque

2016-02-01

Full Text Available Abstract Background Peru has high cervical cancer incidence and mortality rates compared to other Andean countries. Therefore, partnerships between governmental and international organizations have targeted rural areas of Peru to receive cervical cancer screening via outreach campaigns. Previous studies have found a relationship between a person’s social networks and cancer screening behaviors. Screening outreach campaigns conducted by the nonprofit organization CerviCusco created an opportunity for a social network study to examine cervical cancer screening history and social network characteristics in a rural indigenous community that participated in these campaigns in 2012 and 2013. The aim of this study was to explore social network characteristics in this community related to receipt of cervical cancer screening following the campaigns. Methods An egocentric social network questionnaire was used to collect cross-sectional network data on community participants. Each survey participant (ego was asked to name six other women they knew (alters and identify the nature of their relationship or tie (family, friend, neighbor, other, residential closeness (within 5 km, length of time known, frequency of communication, topics of conversation, and whether they lent money to the person, provided childcare or helped with transportation. In addition, each participant was asked to report the nature of the relationship between all alters identified (e.g., friend, family, or neighbor. Bivariate and multivariate analyses were used to explore the relationship between Pap test receipt at the CerviCusco outreach screening campaigns and social network characteristics. Results Bivariate results found significant differences in percentage of alter composition for neighbors and family, and for mean number of years known, mean density, and mean degree centrality between women who had received a Pap test (n = 19 compared to those who had not (n = 50 (p�

Proactive recruitment of cancer patients’ social networks into a smoking cessation trial

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Bastian, Lori A.; Fish, Laura J.; Peterson, Bercedis L.; Biddle, Andrea K.; Garst, Jennifer; Lyna, Pauline; Molner, Stephanie; Bepler, Gerold; Kelley, Mike; Keefe, Francis J.; McBride, Colleen M.

2011-01-01

Background This report describes the characteristics associated with successful enrollment of smokers in the social networks (i.e., family and close friends) of patients with lung cancer into a smoking cessation intervention. Methods Lung cancer patients from four clinical sites were asked to complete a survey enumerating their family members and close friends who smoke, and provide permission to contact these potential participants. Family members and close friends identified as smokers were interviewed and offered participation in a smoking cessation intervention. Repeated measures logistic regression model examined characteristics associated with enrollment. Results A total of 1,062 eligible lung cancer patients were identified and 516 patients consented and completed the survey. These patients identified 1,325 potentially eligible family and close friends. Of these, 496 consented and enrolled in the smoking cessation program. Network enrollment was highest among patients who were white and had late-stage disease. Social network members enrolled were most likely to be female, a birth family, immediate family, or close friend, and live in close geographic proximity to the patient. Conclusions Proactive recruitment of smokers in the social networks of lung cancer patients is challenging. In this study, the majority of family members and friends declined to participate. Enlisting immediate female family members and friends, who live close to the patient as agents to proactively recruit other network members into smoking cessation trials could be used to extend reach of cessation interventions to patients’ social networks. Moreover, further consideration should be given to the appropriate timing of approaching network smokers to consider cessation. PMID:21382509

Non-coding RNA networks in cancer.

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Anastasiadou, Eleni; Jacob, Leni S; Slack, Frank J

2018-01-01

Thousands of unique non-coding RNA (ncRNA) sequences exist within cells. Work from the past decade has altered our perception of ncRNAs from 'junk' transcriptional products to functional regulatory molecules that mediate cellular processes including chromatin remodelling, transcription, post-transcriptional modifications and signal transduction. The networks in which ncRNAs engage can influence numerous molecular targets to drive specific cell biological responses and fates. Consequently, ncRNAs act as key regulators of physiological programmes in developmental and disease contexts. Particularly relevant in cancer, ncRNAs have been identified as oncogenic drivers and tumour suppressors in every major cancer type. Thus, a deeper understanding of the complex networks of interactions that ncRNAs coordinate would provide a unique opportunity to design better therapeutic interventions.

Transduction motif analysis of gastric cancer based on a human signaling network

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Liu, G.; Li, D.Z.; Jiang, C.S.; Wang, W. [Fuzhou General Hospital of Nanjing Command, Department of Gastroenterology, Fuzhou, China, Department of Gastroenterology, Fuzhou General Hospital of Nanjing Command, Fuzhou (China)

2014-04-04

To investigate signal regulation models of gastric cancer, databases and literature were used to construct the signaling network in humans. Topological characteristics of the network were analyzed by CytoScape. After marking gastric cancer-related genes extracted from the CancerResource, GeneRIF, and COSMIC databases, the FANMOD software was used for the mining of gastric cancer-related motifs in a network with three vertices. The significant motif difference method was adopted to identify significantly different motifs in the normal and cancer states. Finally, we conducted a series of analyses of the significantly different motifs, including gene ontology, function annotation of genes, and model classification. A human signaling network was constructed, with 1643 nodes and 5089 regulating interactions. The network was configured to have the characteristics of other biological networks. There were 57,942 motifs marked with gastric cancer-related genes out of a total of 69,492 motifs, and 264 motifs were selected as significantly different motifs by calculating the significant motif difference (SMD) scores. Genes in significantly different motifs were mainly enriched in functions associated with cancer genesis, such as regulation of cell death, amino acid phosphorylation of proteins, and intracellular signaling cascades. The top five significantly different motifs were mainly cascade and positive feedback types. Almost all genes in the five motifs were cancer related, including EPOR, MAPK14, BCL2L1, KRT18, PTPN6, CASP3, TGFBR2, AR, and CASP7. The development of cancer might be curbed by inhibiting signal transductions upstream and downstream of the selected motifs.

Assessing Breast Cancer Risk with an Artificial Neural Network

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Sepandi, Mojtaba; Taghdir, Maryam; Rezaianzadeh, Abbas; Rahimikazerooni, Salar

2018-04-25

Objectives: Radiologists face uncertainty in making decisions based on their judgment of breast cancer risk. Artificial intelligence and machine learning techniques have been widely applied in detection/recognition of cancer. This study aimed to establish a model to aid radiologists in breast cancer risk estimation. This incorporated imaging methods and fine needle aspiration biopsy (FNAB) for cyto-pathological diagnosis. Methods: An artificial neural network (ANN) technique was used on a retrospectively collected dataset including mammographic results, risk factors, and clinical findings to accurately predict the probability of breast cancer in individual patients. Area under the receiver-operating characteristic curve (AUC), accuracy, sensitivity, specificity, and positive and negative predictive values were used to evaluate discriminative performance. Result: The network incorporating the selected features performed best (AUC = 0.955). Sensitivity and specificity of the ANN were respectively calculated as 0.82 and 0.90. In addition, negative and positive predictive values were respectively computed as 0.90 and 0.80. Conclusion: ANN has potential applications as a decision-support tool to help underperforming practitioners to improve the positive predictive value of biopsy recommendations. Creative Commons Attribution License

TROVE: A User-friendly Tool for Visualizing and Analyzing Cancer Hallmarks in Signaling Networks.

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Chua, Huey Eng; Bhowmick, Sourav S; Zheng, Jie

2017-09-22

Cancer hallmarks, a concept that seeks to explain the complexity of cancer initiation and development, provide a new perspective of studying cancer signaling which could lead to a greater understanding of this complex disease. However, to the best of our knowledge, there is currently a lack of tools that support such hallmark-based study of the cancer signaling network, thereby impeding the gain of knowledge in this area. We present TROVE, a user-friendly software that facilitates hallmark annotation, visualization and analysis in cancer signaling networks. In particular, TROVE facilitates hallmark analysis specific to particular cancer types. Available under the Eclipse Public License from: https://sites.google.com/site/cosbyntu/softwares/trove and https://github.com/trove2017/Trove. hechua@ntu.edu.sg or assourav@ntu.edu.sg. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and Epigenetic Network Derived from Next-Generation Sequencing Data.

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Li, Cheng-Wei; Chen, Bor-Sen

2016-01-01

Epigenetic and microRNA (miRNA) regulation are associated with carcinogenesis and the development of cancer. By using the available omics data, including those from next-generation sequencing (NGS), genome-wide methylation profiling, candidate integrated genetic and epigenetic network (IGEN) analysis, and drug response genome-wide microarray analysis, we constructed an IGEN system based on three coupling regression models that characterize protein-protein interaction networks (PPINs), gene regulatory networks (GRNs), miRNA regulatory networks (MRNs), and epigenetic regulatory networks (ERNs). By applying system identification method and principal genome-wide network projection (PGNP) to IGEN analysis, we identified the core network biomarkers to investigate bladder carcinogenic mechanisms and design multiple drug combinations for treating bladder cancer with minimal side-effects. The progression of DNA repair and cell proliferation in stage 1 bladder cancer ultimately results not only in the derepression of miR-200a and miR-200b but also in the regulation of the TNF pathway to metastasis-related genes or proteins, cell proliferation, and DNA repair in stage 4 bladder cancer. We designed a multiple drug combination comprising gefitinib, estradiol, yohimbine, and fulvestrant for treating stage 1 bladder cancer with minimal side-effects, and another multiple drug combination comprising gefitinib, estradiol, chlorpromazine, and LY294002 for treating stage 4 bladder cancer with minimal side-effects.

Comprehensive characterization of lncRNA-mRNA related ceRNA network across 12 major cancers

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Feng, Li; Li, Feng; Sun, Zeguo; Wu, Tan; Shi, Xinrui; Li, Jing; Li, Xia

2016-01-01

Recent studies indicate that long noncoding RNAs (lncRNAs) can act as competing endogenous RNAs (ceRNAs) to indirectly regulate mRNAs through shared microRNAs, which represents a novel layer of RNA crosstalk and plays critical roles in the development of tumor. However, the global regulation landscape and characterization of these lncRNA related ceRNA crosstalk in cancers is still largely unknown. Here, we systematically characterized the lncRNA related ceRNA interactions across 12 major cancers and the normal physiological states by integrating multidimensional molecule profiles of more than 5000 samples. Our study suggest the large difference of ceRNA regulation between normal and tumor states and the higher similarity across similar tissue origin of tumors. The ceRNA related molecules have more conserved features in tumor networks and they play critical roles in both the normal and tumorigenesis processes. Besides, lncRNAs in the pan-cancer ceRNA network may be potential biomarkers of tumor. By exploring hub lncRNAs, we found that these conserved key lncRNAs dominate variable tumor hallmark processes across pan-cancers. Network dynamic analysis highlights the critical roles of ceRNA regulation in tumorigenesis. By analyzing conserved ceRNA interactions, we found that miRNA mediate ceRNA regulation showed different patterns across pan-cancer; while analyzing the cancer specific ceRNA interactions reveal that lncRNAs synergistically regulated tumor driver genes of cancer hallmarks. Finally, we found that ceRNA modules have the potential to predict patient survival. Overall, our study systematically dissected the lncRNA related ceRNA networks in pan-cancer that shed new light on understanding the molecular mechanism of tumorigenesis. PMID:27580177

Drawbacks and benefits associated with inter-organizational collaboration along the discovery-development-delivery continuum: a cancer research network case study.

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Harris, Jenine K; Provan, Keith G; Johnson, Kimberly J; Leischow, Scott J

2012-07-25

The scientific process around cancer research begins with scientific discovery, followed by development of interventions, and finally delivery of needed interventions to people with cancer. Numerous studies have identified substantial gaps between discovery and delivery in health research. Team science has been identified as a possible solution for closing the discovery to delivery gap; however, little is known about effective ways of collaborating within teams and across organizations. The purpose of this study was to determine benefits and drawbacks associated with organizational collaboration across the discovery-development-delivery research continuum. Representatives of organizations working on cancer research across a state answered a survey about how they collaborated with other cancer research organizations in the state and what benefits and drawbacks they experienced while collaborating. We used exponential random graph modeling to determine the association between these benefits and drawbacks and the presence of a collaboration tie between any two network members. Different drawbacks and benefits were associated with discovery, development, and delivery collaborations. The only consistent association across all three was with the drawback of difficulty due to geographic differences, which was negatively associated with collaboration, indicating that those organizations that had collaborated were less likely to perceive a barrier related to geography. The benefit, enhanced access to other knowledge, was positive and significant in the development and delivery networks, indicating that collaborating organizations viewed improved knowledge exchange as a benefit of collaboration. 'Acquisition of additional funding or other resources' and 'development of new tools and methods' were negatively significantly related to collaboration in these networks. So, although improved knowledge access was an outcome of collaboration, more tangible outcomes were not being

The UK-SEA-ME Psychosocial-Cultural Cancer Research Network: setting the stage for applied qualitative research on cancer health behaviour in southeast Asia and the Middle East.

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Lim, Jennifer N W

2011-01-01

Psychosocial and cultural factors influencing cancer health behaviour have not been systematically investigated outside the western culture, and qualitative research is the best approach for this type of social research. The research methods employed to study health problems in Asia predominantly are quantitative techniques. The set up of the first psychosocial cancer research network in Asia marks the beginning of a collaboration to promote and spearhead applied qualitative healthcare research in cancer in the UK, Southeast Asia and the Middle East. This paper sets out the rationale, objectives and mission for the UK-SEA-ME Psychosocial-Cultural Cancer Research Network. The UK-SEA-ME network is made up of collaborators from the University of Leeds (UK), the University of Malaya (Malaysia), the National University of Singapore (Singapore) and the University of United Arab Emirates (UAE). The network promotes applied qualitative research to investigate the psychosocial and cultural factors influencing delayed and late presentation and diagnosis for cancer (breast cancer) in partner countries, as well as advocating the use of the mixed-methods research approach. The network also offers knowledge transfer for capacity building within network universities. The mission of the network is to improve public awareness about the importance of early management and prevention of cancer through research in Asia.

Breast Cancer Diagnosis using Artificial Neural Networks with Extreme Learning Techniques

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Chandra Prasetyo Utomo; Aan Kardiana; Rika Yuliwulandari

2014-01-01

Breast cancer is the second cause of dead among women. Early detection followed by appropriate cancer treatment can reduce the deadly risk. Medical professionals can make mistakes while identifying a disease. The help of technology such as data mining and machine learning can substantially improve the diagnosis accuracy. Artificial Neural Networks (ANN) has been widely used in intelligent breast cancer diagnosis. However, the standard Gradient-Based Back Propagation Artificial Neural Networks...

Analysis of metastasis associated signal regulatory network in colorectal cancer.

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Qi, Lu; Ding, Yanqing

2018-06-18

Metastasis is a key factor that affects the survival and prognosis of colorectal cancer patients. To elucidate molecular mechanism associated with the metastasis of colorectal cancer, genes related to the metastasis time of colorectal cancer were screened. Then, a network was constructed with this genes. Data was obtained from colorectal cancer expression profile. Molecular mechanism elucidated the time of tumor metastasis and the expression of genes related to colorectal cancer. We found that metastasis-promoting and metastasis-inhibiting networks included protein hubs of high connectivity. These protein hubs were components of organelles. Some ribosomal proteins promoted the metastasis of colorectal cancer. In some components of organelles, such as proteasomes, mitochondrial ribosome, ATP synthase, and splicing factors, the metastasis of colorectal cancer was inhibited by some sections of these organelles. After performing survival analysis of proteins in organelles, joint survival curve of proteins was constructed in ribosomal network. This joint survival curve showed metastasis was promoted in patients with colorectal cancer (P = 0.0022939). Joint survival curve of proteins was plotted against proteasomes (P = 7 e-07), mitochondrial ribosome (P = 0.0001157), ATP synthase (P = 0.0001936), and splicing factors (P = 1.35e-05). These curves indicate that metastasis of colorectal cancer can be inhibited. After analyzing proteins that bind with organelle components, we also found that some proteins were associated with the time of colorectal cancer metastasis. Hence, different cellular components play different roles in the metastasis of colorectal cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Inference of cancer-specific gene regulatory networks using soft computing rules.

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Wang, Xiaosheng; Gotoh, Osamu

2010-03-24

Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.

Boolean network model for cancer pathways: predicting carcinogenesis and targeted therapy outcomes.

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Herman F Fumiã

Full Text Available A Boolean dynamical system integrating the main signaling pathways involved in cancer is constructed based on the currently known protein-protein interaction network. This system exhibits stationary protein activation patterns--attractors--dependent on the cell's microenvironment. These dynamical attractors were determined through simulations and their stabilities against mutations were tested. In a higher hierarchical level, it was possible to group the network attractors into distinct cell phenotypes and determine driver mutations that promote phenotypic transitions. We find that driver nodes are not necessarily central in the network topology, but at least they are direct regulators of central components towards which converge or through which crosstalk distinct cancer signaling pathways. The predicted drivers are in agreement with those pointed out by diverse census of cancer genes recently performed for several human cancers. Furthermore, our results demonstrate that cell phenotypes can evolve towards full malignancy through distinct sequences of accumulated mutations. In particular, the network model supports routes of carcinogenesis known for some tumor types. Finally, the Boolean network model is employed to evaluate the outcome of molecularly targeted cancer therapies. The major find is that monotherapies were additive in their effects and that the association of targeted drugs is necessary for cancer eradication.

[Scientific production and cancer-related collaboration networks in Peru 2000-2011: a bibliometric study in Scopus and Science Citation Index].

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Mayta-Tristán, Percy; Huamaní, Charles; Montenegro-Idrogo, Juan José; Samanez-Figari, César; González-Alcaide, Gregorio

2013-03-01

A bibliometric study was carried out to describe the scientific production on cancer written by Peruvians and published in international health journals, as well as to assess the scientific collaboration networks. It included articles on cancer written in Peru between the years 2000 and 2011 and published in health journals indexed in SCOPUS or Science Citation Index Expanded. In the 358 articles identified, an increase in the production was seen, from 4 articles in 2000 to 57 in 2011.The most studied types were cervical cancer (77 publications); breast cancer (53), and gastric cancer (37). The National Institute of Neoplastic Diseases (INEN) was the most productive institution (121 articles) and had the highest number of collaborations (180 different institutions). 52 clinical trials were identified, 29 of which had at least one author from INEN. We can conclude that, cancer research is increasing in Peru, the INEN being the most productive institution, with an important participation in clinical trials.

Classification and diagnostic prediction of cancers using gene expression profiling and artificial neural networks | Center for Cancer Research

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The purpose of this study was to develop a method of classifying cancers to specific diagnostic categories based on their gene expression signatures using artificial neural networks (ANNs). We trained the ANNs using the small, round blue-cell tumors (SRBCTs) as a model. These cancers belong to four distinct diagnostic categories and often present diagnostic dilemmas in

The association between active participation in a sports club, physical activity and social network on the development of lung cancer in smokers: a case-control study

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Schmidt Anna

2012-01-01

Full Text Available Abstract Background This study analyses the effect of active participation in a sports club, physical activity and social networks on the development of lung cancer in patients who smoke. Our hypothesis is that study participants who lack social networks and do not actively participate in a sports club are at a greater risk for lung cancer than those who do. Methods Data for the study were taken from the Cologne Smoking Study (CoSmoS, a retrospective case-control study examining potential psychosocial risk factors for the development of lung cancer. Our sample consisted of n = 158 participants who had suffered lung cancer (diagnosis in the patient document and n = 144 control group participants. Both groups had a history of smoking. Data on social networks were collected by asking participants whether they participated in a sports club and about the number of friends and relatives in their social environment. In addition, sociodemographic data (gender, age, education, marital status, residence and religion, physical activity and data on pack years (the cumulative number of cigarettes smoked by an individual, calculated by multiplying the number of cigarettes smoked per day by the number of years the person has smoked divided by 20 were collected to control for potential confounders. Logistic regression was used for the statistical analysis. Results The results reveal that participants who are physically active are at a lower risk of lung cancer than those who are not (adjusted OR = 0.53*; CI = 0.29-0.97. Older age and lower education seem also to be risk factors for the development of lung cancer. The extent of smoking, furthermore, measured by pack years is statistically significant. Active participation in a sports club, number of friends and relatives had no statistically significant influence on the development of the cancer. Conclusions The results of the study suggest that there is a lower risk for physically active participants to develop

Disparities in Adherence to National Comprehensive Cancer Network Treatment Guidelines and Survival for Stage IB-IIA Cervical Cancer in California.

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Pfaendler, Krista S; Chang, Jenny; Ziogas, Argyrios; Bristow, Robert E; Penner, Kristine R

2018-05-01

To evaluate the association of sociodemographic and hospital characteristics with adherence to National Comprehensive Cancer Network treatment guidelines for stage IB-IIA cervical cancer and to analyze the relationship between adherent care and survival. This is a retrospective population-based cohort study of patients with stage IB-IIA invasive cervical cancer reported to the California Cancer Registry from January 1, 1995, through December 31, 2009. Adherence to National Comprehensive Cancer Network guideline care was defined by year- and stage-appropriate surgical procedures, radiation, and chemotherapy. Multivariate logistic regression, Kaplan-Meier estimate, and Cox proportional hazard models were used to examine associations between patient, tumor, and treatment characteristics and National Comprehensive Cancer Network guideline adherence and cervical cancer-specific 5-year survival. A total of 6,063 patients were identified. Forty-seven percent received National Comprehensive Cancer Network guideline-adherent care, and 18.8% were treated in high-volume centers (20 or more patients/year). On multivariate analysis, lowest socioeconomic status (adjusted odds ratio [OR] 0.69, 95% CI 0.57-0.84), low-middle socioeconomic status (adjusted OR 0.76, 95% CI 0.64-0.92), and Charlson-Deyo comorbidity score 1 or higher (adjusted OR 0.78, 95% CI 0.69-0.89) were patient characteristics associated with receipt of nonguideline care. Receiving adherent care was less common in low-volume centers (45.9%) than in high-volume centers (50.9%) (effect size 0.90, 95% CI 0.84-0.96). Death from cervical cancer was more common in the nonadherent group (13.3%) than in the adherent group (8.6%) (effect size 1.55, 95% CI 1.34-1.80). Black race (adjusted hazard ratio 1.56, 95% CI 1.08-2.27), Medicaid payer status (adjusted hazard ratio 1.47, 95% CI 1.15-1.87), and Charlson-Deyo comorbidity score 1 or higher (adjusted hazard ratio 2.07, 95% CI 1.68-2.56) were all associated with increased

Gene Expression Correlation for Cancer Diagnosis: A Pilot Study

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Binbing Ling

2014-01-01

Full Text Available Poor prognosis for late-stage, high-grade, and recurrent cancers has been motivating cancer researchers to search for more efficient biomarkers to identify the onset of cancer. Recent advances in constructing and dynamically analyzing biomolecular networks for different types of cancer have provided a promising novel strategy to detect tumorigenesis and metastasis. The observation of different biomolecular networks associated with normal and cancerous states led us to hypothesize that correlations for gene expressions could serve as valid indicators of early cancer development. In this pilot study, we tested our hypothesis by examining whether the mRNA expressions of three randomly selected cancer-related genes PIK3C3, PIM3, and PTEN were correlated during cancer progression and the correlation coefficients could be used for cancer diagnosis. Strong correlations (0.68≤r≤1.0 were observed between PIK3C3 and PIM3 in breast cancer, between PIK3C3 and PTEN in breast and ovary cancers, and between PIM3 and PTEN in breast, kidney, liver, and thyroid cancers during disease progression, implicating that the correlations for cancer network gene expressions could serve as a supplement to current clinical biomarkers, such as cancer antigens, for early cancer diagnosis.

A Comprehensive Nuclear Receptor Network for Breast Cancer Cells

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Ralf Kittler

2013-02-01

Full Text Available In breast cancer, nuclear receptors (NRs play a prominent role in governing gene expression, have prognostic utility, and are therapeutic targets. We built a regulatory map for 24 NRs, six chromatin state markers, and 14 breast-cancer-associated transcription factors (TFs that are expressed in the breast cancer cell line MCF-7. The resulting network reveals a highly interconnected regulatory matrix where extensive crosstalk occurs among NRs and other breast -cancer-associated TFs. We show that large numbers of factors are coordinately bound to highly occupied target regions throughout the genome, and these regions are associated with active chromatin state and hormone-responsive gene expression. This network also provides a framework for stratifying and predicting patient outcomes, and we use it to show that the peroxisome proliferator-activated receptor delta binds to a set of genes also regulated by the retinoic acid receptors and whose expression is associated with poor prognosis in breast cancer.

Offline Social Relationships and Online Cancer Communication: Effects of Social and Family Support on Online Social Network Building.

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Namkoong, Kang; Shah, Dhavan V; Gustafson, David H

2017-11-01

This study investigates how social support and family relationship perceptions influence breast cancer patients' online communication networks in a computer-mediated social support (CMSS) group. To examine social interactions in the CMSS group, we identified two types of online social networks: open and targeted communication networks. The open communication network reflects group communication behaviors (i.e., one-to-many or "broadcast" communication) in which the intended audience is not specified; in contrast, the targeted communication network reflects interpersonal discourses (i.e., one-to-one or directed communication) in which the audience for the message is specified. The communication networks were constructed by tracking CMSS group usage data of 237 breast cancer patients who participated in one of two National Cancer Institute-funded randomized clinical trials. Eligible subjects were within 2 months of a diagnosis of primary breast cancer or recurrence at the time of recruitment. Findings reveal that breast cancer patients who perceived less availability of offline social support had a larger social network size in the open communication network. In contrast, those who perceived less family cohesion had a larger targeted communication network in the CMSS group, meaning they were inclined to use the CMSS group for developing interpersonal relationships.

Communication networks of men facing a diagnosis of prostate cancer.

Science.gov (United States)

Brown, Dot; Oetzel, John; Henderson, Alison

2016-11-01

This study seeks to identify the factors that shape the communication networks of men who face a potential diagnosis of prostate cancer, and how these factors relate to their disclosure about their changing health status. Men facing a potential diagnosis of prostate cancer are in a challenging situation; the support benefits of disclosing their changing health status to others in their communication networks is set against a backdrop of the potential stigma and uncertainty of the diagnosis. All men on a prostate biopsy waiting list were eligible for inclusion in an exploratory and interpretive study. Semi-structured interviews with 40 men explored their network structures and disclosure of health information. Thematic analysis highlighted the factors which contributed to their network structures and their disclosure about their health status. Four network factors shaped men's perspectives about disclosing their health status: (1) tie strength, comprising both strong and weak ties; (2) knowledgeable others, with a focus on medical professionals in the family; (3) homophily, which included other individuals with a similar medical condition; and (4) geographical proximity, with a preference for face-to-face communication. Communication networks influence men's disclosure of their health status and in particular weak ties with medical knowledge have an important role. Men who use the potential for support in their networks may experience improved psychosocial outcomes. Using these four network factors-tie strength, knowledgeable others, homophily or geographical proximity-to forecast men's willingness to disclose helps identify men who lack potential support and so are at risk of poor psychosocial health. Those with few strong ties or knowledgeable others in their networks may be in the at-risk cohort. The support provided in communication networks complements formal medical care from nurses and other health professionals, and encouraging patients to use their

Social networks, social support mechanisms, and quality of life after breast cancer diagnosis.

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Kroenke, Candyce H; Kwan, Marilyn L; Neugut, Alfred I; Ergas, Isaac J; Wright, Jaime D; Caan, Bette J; Hershman, Dawn; Kushi, Lawrence H

2013-06-01

We examined mechanisms through which social relationships influence quality of life (QOL) in breast cancer survivors. This study included 3,139 women from the Pathways Study who were diagnosed with breast cancer from 2006 to 2011 and provided data on social networks (the presence of a spouse or intimate partner, religious/social ties, volunteering, and numbers of close friends and relatives), social support (tangible support, emotional/informational support, affection, positive social interaction), and QOL, measured by the FACT-B, approximately 2 months post diagnosis. We used logistic models to evaluate associations between social network size, social support, and lower versus higher than median QOL scores. We further stratified by stage at diagnosis and treatment. In multivariate-adjusted analyses, women who were characterized as socially isolated had significantly lower FACT-B (OR = 2.18, 95 % CI: 1.72-2.77), physical well-being (WB) (OR = 1.61, 95 % CI: 1.27-2.03), functional WB (OR = 2.08, 95 % CI: 1.65-2.63), social WB (OR = 3.46, 95 % CI: 2.73-4.39), and emotional WB (OR = 1.67, 95 % CI: 1.33-2.11) scores and higher breast cancer symptoms (OR = 1.48, 95 % CI: 1.18-1.87) compared with socially integrated women. Each social network member independently predicted higher QOL. Simultaneous adjustment for social networks and social support partially attenuated associations between social networks and QOL. The strongest mediator and type of social support that was most predictive of QOL outcomes was "positive social interaction." However, each type of support was important depending on outcome, stage, and treatment status. Larger social networks and greater social support were related to higher QOL after a diagnosis of breast cancer. Effective social support interventions need to evolve beyond social-emotional interventions and need to account for disease severity and treatment status.

Social networks, social support mechanisms, and quality of life after breast cancer diagnosis

Science.gov (United States)

Kroenke, Candyce H; Kwan, Marilyn L.; Neugut, Alfred I.; Ergas, Isaac J.; Wright, Jaime D.; Caan, Bette J.; Hershman, Dawn; Kushi, Lawrence H.

2013-01-01

Purpose We examined mechanisms through which social relationships influence quality of life (QOL) in breast cancer survivors. Methods This study included 3,139 women from the Pathways Study who were diagnosed with breast cancer from 2006-2011 and provided data on social networks (presence of spouse or intimate partner, religious/social ties, volunteering, and numbers of close friends and relatives), social support (tangible, emotional/informational, affection, positive social interaction), and quality of life (QOL), measured by the FACT-B, approximately two months post-diagnosis. We used logistic models to evaluate associations between social network size, social support, and lower vs. higher than median QOL scores. We further stratified by stage at diagnosis and treatment. Results In multivariate-adjusted analyses, women who were characterized as socially isolated had significantly lower FACT-B (OR=2.18, 95%CI:1.72-2.77), physical well-being (WB) (OR=1.61, 95%CI:1.27-2.03), functional WB (OR=2.08, 95%CI:1.65-2.63), social WB (OR=3.46, 95%CI:2.73-4.39), and emotional WB (OR=1.67, 95%CI:1.33-2.11) scores and higher breast cancer symptoms (OR=1.48, 95%CI:1.18-1.87), compared with socially integrated women. Each social network member independently predicted higher QOL. Simultaneous adjustment for social networks and social support partially attenuated associations between social networks and QOL. The strongest mediator and type of social support that was most predictive of QOL outcomes was “positive social interaction”. However, each type of support was important depending on outcome, stage, and treatment status. Conclusions Larger social networks and greater social support were related to higher QOL after a diagnosis of breast cancer. Effective social support interventions need to evolve beyond social-emotional interventions and need to account for disease severity and treatment status. PMID:23657404

Inference of Cancer-specific Gene Regulatory Networks Using Soft Computing Rules

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Xiaosheng Wang

2010-03-01

Full Text Available Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.

Cancer association study of aminoacyl-tRNA synthetase signaling network in glioblastoma.

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Yong-Wan Kim

Full Text Available Aminoacyl-tRNA synthetases (ARSs and ARS-interacting multifunctional proteins (AIMPs exhibit remarkable functional versatility beyond their catalytic activities in protein synthesis. Their non-canonical functions have been pathologically linked to cancers. Here we described our integrative genome-wide analysis of ARSs to show cancer-associated activities in glioblastoma multiforme (GBM, the most aggressive malignant primary brain tumor. We first selected 23 ARS/AIMPs (together referred to as ARSN, 124 cancer-associated druggable target genes (DTGs and 404 protein-protein interactors (PPIs of ARSs using NCI's cancer gene index. 254 GBM affymetrix microarray data in The Cancer Genome Atlas (TCGA were used to identify the probe sets whose expression were most strongly correlated with survival (Kaplan-Meier plots versus survival times, log-rank t-test <0.05. The analysis identified 122 probe sets as survival signatures, including 5 of ARSN (VARS, QARS, CARS, NARS, FARS, and 115 of DTGs and PPIs (PARD3, RXRB, ATP5C1, HSP90AA1, CD44, THRA, TRAF2, KRT10, MED12, etc. Of note, 61 survival-related probes were differentially expressed in three different prognosis subgroups in GBM patients and showed correlation with established prognosis markers such as age and phenotypic molecular signatures. CARS and FARS also showed significantly higher association with different molecular networks in GBM patients. Taken together, our findings demonstrate evidence for an ARSN biology-dominant contribution in the biology of GBM.

The National Cancer Institute's Physical Sciences - Oncology Network

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Espey, Michael Graham

In 2009, the NCI launched the Physical Sciences - Oncology Centers (PS-OC) initiative with 12 Centers (U54) funded through 2014. The current phase of the Program includes U54 funded Centers with the added feature of soliciting new Physical Science - Oncology Projects (PS-OP) U01 grant applications through 2017; see NCI PAR-15-021. The PS-OPs, individually and along with other PS-OPs and the Physical Sciences-Oncology Centers (PS-OCs), comprise the Physical Sciences-Oncology Network (PS-ON). The foundation of the Physical Sciences-Oncology initiative is a high-risk, high-reward program that promotes a `physical sciences perspective' of cancer and fosters the convergence of physical science and cancer research by forming transdisciplinary teams of physical scientists (e.g., physicists, mathematicians, chemists, engineers, computer scientists) and cancer researchers (e.g., cancer biologists, oncologists, pathologists) who work closely together to advance our understanding of cancer. The collaborative PS-ON structure catalyzes transformative science through increased exchange of people, ideas, and approaches. PS-ON resources are leveraged to fund Trans-Network pilot projects to enable synergy and cross-testing of experimental and/or theoretical concepts. This session will include a brief PS-ON overview followed by a strategic discussion with the APS community to exchange perspectives on the progression of trans-disciplinary physical sciences in cancer research.

Cancer signaling networks and their implications for personalized medicine

DEFF Research Database (Denmark)

Creixell, Pau

Amongst the unique features of cancer cells perhaps the most crucial one is the change in the cellular decision-making process. While both non-cancer and cancer cells are constantly integrating different external cues that reach them and computing cellular decisions (e.g. proliferation or apoptosis......) based on the integration of these cues; this integration and consequently the cellular decisions taken by cancer cells are arguably very distinct from the decisions that would be expected from non-cancer cells. Since cellular signaling networks and its different states are the computational circuits...

MicroRNA functional network in pancreatic cancer: From biology to ...

Indian Academy of Sciences (India)

[Wang J and Sen S 2011 MicroRNA functional network in pancreatic cancer: From biology to biomarkers of disease. ... growth factor type I receptor; INSR, insulin receptor; IPA, Ingenuity Pathway Analysis; IPMN, ..... Prostate cancer signalling.

The meaning and validation of social support networks for close family of persons with advanced cancer.

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Sjolander, Catarina; Ahlstrom, Gerd

2012-09-17

To strengthen the mental well-being of close family of persons newly diagnosed as having cancer, it is necessary to acquire a greater understanding of their experiences of social support networks, so as to better assess what resources are available to them from such networks and what professional measures are required. The main aim of the present study was to explore the meaning of these networks for close family of adult persons in the early stage of treatment for advanced lung or gastrointestinal cancer. An additional aim was to validate the study's empirical findings by means of the Finfgeld-Connett conceptual model for social support. The intention was to investigate whether these findings were in accordance with previous research in nursing. Seventeen family members with a relative who 8-14 weeks earlier had been diagnosed as having lung or gastrointestinal cancer were interviewed. The data were subjected to qualitative latent content analysis and validated by means of identifying antecedents and critical attributes. The meaning or main attribute of the social support network was expressed by the theme Confirmation through togetherness, based on six subthemes covering emotional and, to a lesser extent, instrumental support. Confirmation through togetherness derived principally from information, understanding, encouragement, involvement and spiritual community. Three subthemes were identified as the antecedents to social support: Need of support, Desire for a deeper relationship with relatives, Network to turn to. Social support involves reciprocal exchange of verbal and non-verbal information provided mainly by lay persons. The study provides knowledge of the antecedents and attributes of social support networks, particularly from the perspective of close family of adult persons with advanced lung or gastrointestinal cancer. There is a need for measurement instruments that could encourage nurses and other health-care professionals to focus on family members

Rural Health Networks: How Network Analysis Can Inform Patient Care and Organizational Collaboration in a Rural Breast Cancer Screening Network.

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Prusaczyk, Beth; Maki, Julia; Luke, Douglas A; Lobb, Rebecca

2018-04-15

Rural health networks have the potential to improve health care quality and access. Despite this, the use of network analysis to study rural health networks is limited. The purpose of this study was to use network analysis to understand how a network of rural breast cancer care providers deliver services and to demonstrate the value of this methodology in this research area. Leaders at 47 Federally Qualified Health Centers and Rural Health Clinics across 10 adjacent rural counties were asked where they refer patients for mammograms or breast biopsies. These clinics and the 22 referral providers that respondents named comprised the network. The network was analyzed graphically and statistically with exponential random graph modeling. Most (96%, n = 45) of the clinics and referral sites (95%, n = 21) are connected to each other. Two clinics of the same type were 62% less likely to refer patients to the same providers as 2 clinics of different types (OR = 0.38, 95% CI = 0.29-0.50). Clinics in the same county have approximately 8 times higher odds of referring patients to the same providers compared to clinics in different counties (OR = 7.80, CI = 4.57-13.31). This study found that geographic location of resources is an important factor in rural health care providers' referral decisions and demonstrated the usefulness of network analysis for understanding rural health networks. These results can be used to guide delivery of patient care and strengthen the network by building resources that take location into account. © 2018 National Rural Health Association.

Social ties and risk for cancer - a prospective cohort study

DEFF Research Database (Denmark)

Bergelt, Corinna; Prescott, Eva; Grønbaek, Morten

2009-01-01

consisted of 8 548 Danes who had been examined in 1991-1994 within the Copenhagen City Heart Study. The median length of follow-up was 9.3 years (range, 0-11.2 years). Social ties were measured from answers to a questionnaire on social networks. Regression analyses for cancers at the most frequent sites......BACKGROUND: Poor social support and small social networks have been associated with increased risks for conditions such as coronary heart disease as well as with overall mortality. We investigated the association between social ties and risk for cancer. MATERIAL AND METHODS: The study sample...... (breast, lung, prostate and colon and rectum) were conducted with the Cox proportional hazards model, with adjustment for a number of well-known risk factors for cancer. RESULTS: While we found no significant association between social ties and risk for cancer in men, women with high social network scores...

Social ties and risk for cancer - a prospective cohort study

DEFF Research Database (Denmark)

Bergelt, C.; Prescott, E.; Gronbaek, M.

2009-01-01

consisted of 8 548 Danes who had been examined in 1991-1994 within the Copenhagen City Heart Study. The median length of follow-up was 9.3 years (range, 0-11.2 years). Social ties were measured from answers to a questionnaire on social networks. Regression analyses for cancers at the most frequent sites......Background. Poor social support and small social networks have been associated with increased risks for conditions such as coronary heart disease as well as with overall mortality. We investigated the association between social ties and risk for cancer. Material and methods. The study sample...... (breast, lung, prostate and colon and rectum) were conducted with the Cox proportional hazards model, with adjustment for a number of well-known risk factors for cancer. Results. While we found no significant association between social ties and risk for cancer in men, women with high social network scores...

Identifying Cancer Subtypes from miRNA-TF-mRNA Regulatory Networks and Expression Data.

Directory of Open Access Journals (Sweden)

Taosheng Xu

Full Text Available Identifying cancer subtypes is an important component of the personalised medicine framework. An increasing number of computational methods have been developed to identify cancer subtypes. However, existing methods rarely use information from gene regulatory networks to facilitate the subtype identification. It is widely accepted that gene regulatory networks play crucial roles in understanding the mechanisms of diseases. Different cancer subtypes are likely caused by different regulatory mechanisms. Therefore, there are great opportunities for developing methods that can utilise network information in identifying cancer subtypes.In this paper, we propose a method, weighted similarity network fusion (WSNF, to utilise the information in the complex miRNA-TF-mRNA regulatory network in identifying cancer subtypes. We firstly build the regulatory network where the nodes represent the features, i.e. the microRNAs (miRNAs, transcription factors (TFs and messenger RNAs (mRNAs and the edges indicate the interactions between the features. The interactions are retrieved from various interatomic databases. We then use the network information and the expression data of the miRNAs, TFs and mRNAs to calculate the weight of the features, representing the level of importance of the features. The feature weight is then integrated into a network fusion approach to cluster the samples (patients and thus to identify cancer subtypes. We applied our method to the TCGA breast invasive carcinoma (BRCA and glioblastoma multiforme (GBM datasets. The experimental results show that WSNF performs better than the other commonly used computational methods, and the information from miRNA-TF-mRNA regulatory network contributes to the performance improvement. The WSNF method successfully identified five breast cancer subtypes and three GBM subtypes which show significantly different survival patterns. We observed that the expression patterns of the features in some mi

Application of artificial neural network model combined with four biomarkers in auxiliary diagnosis of lung cancer.

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Duan, Xiaoran; Yang, Yongli; Tan, Shanjuan; Wang, Sihua; Feng, Xiaolei; Cui, Liuxin; Feng, Feifei; Yu, Songcheng; Wang, Wei; Wu, Yongjun

2017-08-01

The purpose of the study was to explore the application of artificial neural network model in the auxiliary diagnosis of lung cancer and compare the effects of back-propagation (BP) neural network with Fisher discrimination model for lung cancer screening by the combined detections of four biomarkers of p16, RASSF1A and FHIT gene promoter methylation levels and the relative telomere length. Real-time quantitative methylation-specific PCR was used to detect the levels of three-gene promoter methylation, and real-time PCR method was applied to determine the relative telomere length. BP neural network and Fisher discrimination analysis were used to establish the discrimination diagnosis model. The levels of three-gene promoter methylation in patients with lung cancer were significantly higher than those of the normal controls. The values of Z(P) in two groups were 2.641 (0.008), 2.075 (0.038) and 3.044 (0.002), respectively. The relative telomere lengths of patients with lung cancer (0.93 ± 0.32) were significantly lower than those of the normal controls (1.16 ± 0.57), t = 4.072, P < 0.001. The areas under the ROC curve (AUC) and 95 % CI of prediction set from Fisher discrimination analysis and BP neural network were 0.670 (0.569-0.761) and 0.760 (0.664-0.840). The AUC of BP neural network was higher than that of Fisher discrimination analysis, and Z(P) was 0.76. Four biomarkers are associated with lung cancer. BP neural network model for the prediction of lung cancer is better than Fisher discrimination analysis, and it can provide an excellent and intelligent diagnosis tool for lung cancer.

Artificial neural networks as classification and diagnostic tools for lymph node-negative breast cancers

Energy Technology Data Exchange (ETDEWEB)

Eswari J, Satya; Chandrakar, Neha [National Institute of Technology Raipur, Raipur (India)

2016-04-15

Artificial neural networks (ANNs) can be used to develop a technique to classify lymph node negative breast cancer that is prone to distant metastases based on gene expression signatures. The neural network used is a multilayered feed forward network that employs back propagation algorithm. Once trained with DNA microarraybased gene expression profiles of genes that were predictive of distant metastasis recurrence of lymph node negative breast cancer, the ANNs became capable of correctly classifying all samples and recognizing the genes most appropriate to the classification. To test the ability of the trained ANN models in recognizing lymph node negative breast cancer, we analyzed additional idle samples that were not used beforehand for the training procedure and obtained the correctly classified result in the validation set. For more substantial result, bootstrapping of training and testing dataset was performed as external validation. This study illustrates the potential application of ANN for breast tumor diagnosis and the identification of candidate targets in patients for therapy.

A research about breast cancer detection using different neural networks and K-MICA algorithm

Directory of Open Access Journals (Sweden)

A A Kalteh

2013-01-01

Full Text Available Breast cancer is the second leading cause of death for women all over the world. The correct diagnosis of breast cancer is one of the major problems in the medical field. From the literature it has been found that different pattern recognition techniques can help them to improve in this domain. This paper presents a novel hybrid intelligent method for detection of breast cancer. The proposed method includes two main modules: Clustering module and the classifier module. In the clustering module, first the input data will be clustered by a new technique. This technique is a suitable combination of the modified imperialist competitive algorithm (MICA and K-means algorithm. Then the Euclidean distance of each pattern is computed from the determined clusters. The classifier module determines the membership of the patterns using the computed distance. In this module, several neural networks, such as the multilayer perceptron, probabilistic neural networks and the radial basis function neural networks are investigated. Using the experimental study, we choose the best classifier in order to recognize the breast cancer. The proposed system is tested on Wisconsin Breast Cancer (WBC database and the simulation results show that the recommended system has high accuracy.

Toward standardizing and reporting colorectal cancer screening indicators on an international level: The International Colorectal Cancer Screening Network

NARCIS (Netherlands)

Benson, Victoria S.; Atkin, Wendy S.; Green, Jane; Nadel, Marion R.; Patnick, Julietta; Smith, Robert A.; Villain, Patricia; Patnick, J.; Atkin, W. S.; Altenhofen, L.; Ancelle-Park, R.; Benson, V. S.; Green, J.; Levin, T. R.; Moss, S. M.; Nadel, M.; Ransohoff, D.; Segnan, N.; Smith, R. A.; Villain, P.; Weller, D.; Koukari, A.; Young, G.; López-Kostner, F.; Antoljak, N.; Suchánek, S.; Zavoral, M.; Holten, I.; Malila, N.; Salines, E.; Brenner, G.; Herszényi, L.; Tulassay, Z.; Rennert, G.; Senore, C.; Zappa, M.; Zorzi, M.; Saito, H.; Leja, M.; Dekker, E.; Jansen, J.; Hol, L.; Kuipers, E.; Kaminski, M. F.; Regula, J.; Sfarti, C.; Trifan, A.; Tang, C.-L.; Hrcka, R.; Binefa, G.; Espinàs, J. A.; Peris, M.; Chen, T. H.; Steele, R.; Pou, G.; Bisges, D.; Dwyer, D.; Groves, C.; Courteau, S.; Kramer, R.; Siegenthaler, K.; Lane, D.; Herrera, C.; Rogers, J.; Rojewski, M.; Wolf, Holly; Sung, J. J.; Ling, K.; Bryant, H.; Rabeneck, L.; Dale, J.; Sware, L.; Yang, H.; Viguier, J.; Von Karsa, L.; Kupcinskas, L.; Deutekom, M.; Törnberg, S.; Austoker, J.; Beral, V.; Monk, C.; Valori, R.; Watson, J.; Kobrin, S.; Pignone, M.; Taplin, S.

2012-01-01

The International Colorectal Cancer Screening Network was established in 2003 to promote best practice in the delivery of organized colorectal cancer screening programs. To facilitate evaluation of such programs, we defined a set of universally applicable colorectal cancer screening measures and

Competing endogenous RNA network analysis identifies critical genes among the different breast cancer subtypes.

Science.gov (United States)

Chen, Juan; Xu, Juan; Li, Yongsheng; Zhang, Jinwen; Chen, Hong; Lu, Jianping; Wang, Zishan; Zhao, Xueying; Xu, Kang; Li, Yixue; Li, Xia; Zhang, Yan

2017-02-07

Although competing endogenous RNAs (ceRNAs) have been implicated in many solid tumors, their roles in breast cancer subtypes are not well understood. We therefore generated a ceRNA network for each subtype based on the significance of both, positive co-expression and the shared miRNAs, in the corresponding subtype miRNA dys-regulatory network, which was constructed based on negative regulations between differentially expressed miRNAs and targets. All four subtype ceRNA networks exhibited scale-free architecture and showed that the common ceRNAs were at the core of the networks. Furthermore, the common ceRNA hubs had greater connectivity than the subtype-specific hubs. Functional analysis of the common subtype ceRNA hubs highlighted factors involved in proliferation, MAPK signaling pathways and tube morphogenesis. Subtype-specific ceRNA hubs highlighted unique subtype-specific pathways, like the estrogen response and inflammatory pathways in the luminal subtypes or the factors involved in the coagulation process that participates in the basal-like subtype. Ultimately, we identified 29 critical subtype-specific ceRNA hubs that characterized the different breast cancer subtypes. Our study thus provides new insight into the common and specific subtype ceRNA interactions that define the different categories of breast cancer and enhances our understanding of the pathology underlying the different breast cancer subtypes, which can have prognostic and therapeutic implications in the future.

An integrative -omics approach to identify functional sub-networks in human colorectal cancer.

Directory of Open Access Journals (Sweden)

Rod K Nibbe

2010-01-01

Full Text Available Emerging evidence indicates that gene products implicated in human cancers often cluster together in "hot spots" in protein-protein interaction (PPI networks. Additionally, small sub-networks within PPI networks that demonstrate synergistic differential expression with respect to tumorigenic phenotypes were recently shown to be more accurate classifiers of disease progression when compared to single targets identified by traditional approaches. However, many of these studies rely exclusively on mRNA expression data, a useful but limited measure of cellular activity. Proteomic profiling experiments provide information at the post-translational level, yet they generally screen only a limited fraction of the proteome. Here, we demonstrate that integration of these complementary data sources with a "proteomics-first" approach can enhance the discovery of candidate sub-networks in cancer that are well-suited for mechanistic validation in disease. We propose that small changes in the mRNA expression of multiple genes in the neighborhood of a protein-hub can be synergistically associated with significant changes in the activity of that protein and its network neighbors. Further, we hypothesize that proteomic targets with significant fold change between phenotype and control may be used to "seed" a search for small PPI sub-networks that are functionally associated with these targets. To test this hypothesis, we select proteomic targets having significant expression changes in human colorectal cancer (CRC from two independent 2-D gel-based screens. Then, we use random walk based models of network crosstalk and develop novel reference models to identify sub-networks that are statistically significant in terms of their functional association with these proteomic targets. Subsequently, using an information-theoretic measure, we evaluate synergistic changes in the activity of identified sub-networks based on genome-wide screens of mRNA expression in CRC

RNA binding protein RNPC1 inhibits breast cancer cells metastasis via activating STARD13-correlated ceRNA network.

Science.gov (United States)

Zhang, Zhiting; Guo, Qianqian; Zhang, Shufang; Xiang, Chenxi; Guo, Xinwei; Zhang, Feng; Gao, Lanlan; Ni, Haiwei; Xi, Tao; Zheng, Lufeng

2018-05-07

RNA binding proteins (RBPs) are pivotal post-transcriptional regulators. RNPC1, an RBP, acts as a tumor suppressor through binding and regulating the expression of target genes in cancer cells. This study disclosed that RNPC1 expression was positively correlated with breast cancer patients' relapse free and overall survival, and RNPC1suppressed breast cancer cells metastasis. Mechanistically, RNPC1 promoting a competing endogenous network (ceRNA) crosstalk between STARD13, CDH5, HOXD10, and HOXD1 (STARD13-correlated ceRNA network) that we previously confirmed in breast cancer cells through stabilizing the transcripts and thus facilitating the expression of these four genes in breast cancer cells. Furthermore, RNPC1 overexpression restrained the promotion of STARD13, CDH5, HOXD10, and HOXD1 knockdown on cell metastasis. Notably, RNPC1 expression was positively correlated with CDH5, HOXD1 and HOXD10 expression in breast cancer tissues, and attenuated adriamycin resistance. Taken together, these results identified that RNPC1 could inhibit breast cancer cells metastasis via promoting STARD13-correlated ceRNA network.

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

NARCIS (Netherlands)

Schaub, Franz X.; Dhankani, Varsha; Berger, Ashton C.; Trivedi, Mihir; Richardson, Anne B.; Shaw, Reid; Zhao, Wei; Zhang, Xiaoyang; Ventura, Andrea; Liu, Yuexin; Ayer, Donald E.; Hurlin, Peter J.; Cherniack, Andrew D.; Eisenman, Robert N.; Bernard, Brady; Grandori, Carla; Caesar-Johnson, Samantha J.; Demchok, John A.; Felau, Ina; Kasapi, Melpomeni; Ferguson, Martin L.; Hutter, Carolyn M.; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Cho, Juok; DeFreitas, Timothy; Frazer, Scott; Gehlenborg, Nils; Getz, Gad; Heiman, David I.; Kim, Jaegil; Lawrence, Michael S.; Lin, Pei; Meier, Sam; Noble, Michael S.; Saksena, Gordon; Voet, Doug; Zhang, Hailei; Bernard, Brady; Chambwe, Nyasha; Dhankani, Varsha; Knijnenburg, Theo; Kramer, Roger; Leinonen, Kalle; Liu, Yuexin; Miller, Michael; Reynolds, Sheila; Shmulevich, Ilya; Thorsson, Vesteinn; Zhang, Wei; Akbani, Rehan; Broom, Bradley M.; Hegde, Apurva M.; Ju, Zhenlin; Kanchi, Rupa S.; Korkut, Anil; Li, Jun; Liang, Han; Ling, Shiyun; Liu, Wenbin; Lu, Yiling; Mills, Gordon B.; Ng, Kwok Shing; Rao, Arvind; Ryan, Michael; Wang, Jing; Weinstein, John N.; Zhang, Jiexin; Abeshouse, Adam; Armenia, Joshua; Chakravarty, Debyani; Chatila, Walid K.; de Bruijn, Ino; Gao, Jianjiong; Gross, Benjamin E.; Heins, Zachary J.; Kundra, Ritika; La, Konnor; Ladanyi, Marc; Luna, Augustin; Nissan, Moriah G.; Ochoa, Angelica; Phillips, Sarah M.; Reznik, Ed; Sanchez-Vega, Francisco; Sander, Chris; Schultz, Nikolaus; Sheridan, Robert; Sumer, S. Onur; Sun, Yichao; Taylor, Barry S.; Wang, Jioajiao; Zhang, Hongxin; Anur, Pavana; Peto, Myron; Spellman, Paul; Benz, Christopher; Stuart, Joshua M.; Wong, Christopher K.; Yau, Christina; Hayes, D. Neil; Parker, Joel S.; Wilkerson, Matthew D.; Ally, Adrian; Balasundaram, Miruna; Bowlby, Reanne; Brooks, Denise; Carlsen, Rebecca; Chuah, Eric; Dhalla, Noreen; Holt, Robert; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen; Robertson, A. Gordon; Sadeghi, Sara; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Tse, Kane; Wong, Tina; Berger, Ashton C.; Beroukhim, Rameen; Cherniack, Andrew D.; Cibulskis, Carrie; Gabriel, Stacey B.; Gao, Galen F.; Ha, Gavin; Meyerson, Matthew; Schumacher, Steven E.; Shih, Juliann; Kucherlapati, Melanie H.; Kucherlapati, Raju S.; Baylin, Stephen; Cope, Leslie; Danilova, Ludmila; Bootwalla, Moiz S.; Lai, Phillip H.; Maglinte, Dennis T.; Van Den Berg, David J.; Weisenberger, Daniel J.; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Fan, Cheng; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Perou, Amy H.; Perou, Charles M.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Skelly, Tara; Soloway, Matthew G.; Tan, Donghui; Veluvolu, Umadevi; Fan, Huihui; Hinoue, Toshinori; Laird, Peter W.; Shen, Hui; Zhou, Wanding; Bellair, Michelle; Chang, Kyle; Covington, Kyle; Creighton, Chad J.; Dinh, Huyen; Doddapaneni, Harsha Vardhan; Donehower, Lawrence A.; Drummond, Jennifer; Gibbs, Richard A.; Glenn, Robert; Hale, Walker; Han, Yi; Hu, Jianhong; Korchina, Viktoriya; Lee, Sandra; Lewis, Lora; Li, Wei; Liu, Xiuping; Morgan, Margaret; Morton, Donna; Muzny, Donna; Santibanez, Jireh; Sheth, Margi; Shinbrot, Eve; Wang, Linghua; Wang, Min; Wheeler, David A.; Xi, Liu; Zhao, Fengmei; Hess, Julian; Appelbaum, Elizabeth L.; Bailey, Matthew; Cordes, Matthew G.; Ding, Li; Fronick, Catrina C.; Fulton, Lucinda A.; Fulton, Robert S.; Kandoth, Cyriac; Mardis, Elaine R.; McLellan, Michael D.; Miller, Christopher A.; Schmidt, Heather K.; Wilson, Richard K.; Crain, Daniel; Curley, Erin; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Penny, Robert; Shelton, Candace; Shelton, Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Wise, Lisa; Zmuda, Erik; Corcoran, Niall; Costello, Tony; Hovens, Christopher; Carvalho, Andre L.; de Carvalho, Ana C.; Fregnani, José H.; Longatto-Filho, Adhemar; Reis, Rui M.; Scapulatempo-Neto, Cristovam; Silveira, Henrique C.S.; Vidal, Daniel O.; Burnette, Andrew; Eschbacher, Jennifer; Hermes, Beth; Noss, Ardene; Singh, Rosy; Anderson, Matthew L.; Castro, Patricia D.; Ittmann, Michael; Huntsman, David; Kohl, Bernard; Le, Xuan; Thorp, Richard; Andry, Chris; Duffy, Elizabeth R.; Lyadov, Vladimir; Paklina, Oxana; Setdikova, Galiya; Shabunin, Alexey; Tavobilov, Mikhail; McPherson, Christopher; Warnick, Ronald; Berkowitz, Ross; Cramer, Daniel; Feltmate, Colleen; Horowitz, Neil; Kibel, Adam; Muto, Michael; Raut, Chandrajit P.; Malykh, Andrei; Barnholtz-Sloan, Jill S.; Barrett, Wendi; Devine, Karen; Fulop, Jordonna; Ostrom, Quinn T.; Shimmel, Kristen; Wolinsky, Yingli; Sloan, Andrew E.; De Rose, Agostino; Giuliante, Felice; Goodman, Marc; Karlan, Beth Y.; Hagedorn, Curt H.; Eckman, John; Harr, Jodi; Myers, Jerome; Tucker, Kelinda; Zach, Leigh Anne; Deyarmin, Brenda; Hu, Hai; Kvecher, Leonid; Larson, Caroline; Mural, Richard J.; Somiari, Stella; Vicha, Ales; Zelinka, Tomas; Bennett, Joseph; Iacocca, Mary; Rabeno, Brenda; Swanson, Patricia; Latour, Mathieu; Lacombe, Louis; Têtu, Bernard; Bergeron, Alain; McGraw, Mary; Staugaitis, Susan M.; Chabot, John; Hibshoosh, Hanina; Sepulveda, Antonia; Su, Tao; Wang, Timothy; Potapova, Olga; Voronina, Olga; Desjardins, Laurence; Mariani, Odette; Roman-Roman, Sergio; Sastre, Xavier; Stern, Marc Henri; Cheng, Feixiong; Signoretti, Sabina; Berchuck, Andrew; Bigner, Darell; Lipp, Eric; Marks, Jeffrey; McCall, Shannon; McLendon, Roger; Secord, Angeles; Sharp, Alexis; Behera, Madhusmita; Brat, Daniel J.; Chen, Amy; Delman, Keith; Force, Seth; Khuri, Fadlo; Magliocca, Kelly; Maithel, Shishir; Olson, Jeffrey J.; Owonikoko, Taofeek; Pickens, Alan; Ramalingam, Suresh; Shin, Dong M.; Sica, Gabriel; Van Meir, Erwin G.; Zhang, Hongzheng; Eijckenboom, Wil; Gillis, Ad; Korpershoek, Esther; Looijenga, Leendert; Oosterhuis, Wolter; Stoop, Hans; van Kessel, Kim E.; Zwarthoff, Ellen C.; Calatozzolo, Chiara; Cuppini, Lucia; Cuzzubbo, Stefania; DiMeco, Francesco; Finocchiaro, Gaetano; Mattei, Luca; Perin, Alessandro; Pollo, Bianca; Chen, Chu; Houck, John; Lohavanichbutr, Pawadee; Hartmann, Arndt; Stoehr, Christine; Stoehr, Robert; Taubert, Helge; Wach, Sven; Wullich, Bernd; Kycler, Witold; Murawa, Dawid; Wiznerowicz, Maciej; Chung, Ki; Edenfield, W. Jeffrey; Martin, Julie; Baudin, Eric; Bubley, Glenn; Bueno, Raphael; De Rienzo, Assunta; Richards, William G.; Kalkanis, Steven; Mikkelsen, Tom; Noushmehr, Houtan; Scarpace, Lisa; Girard, Nicolas; Aymerich, Marta; Campo, Elias; Giné, Eva; Guillermo, Armando López; Van Bang, Nguyen; Hanh, Phan Thi; Phu, Bui Duc; Tang, Yufang; Colman, Howard; Evason, Kimberley; Dottino, Peter R.; Martignetti, John A.; Gabra, Hani; Juhl, Hartmut; Akeredolu, Teniola; Stepa, Serghei; Hoon, Dave; Ahn, Keunsoo; Kang, Koo Jeong; Beuschlein, Felix; Breggia, Anne; Birrer, Michael; Bell, Debra; Borad, Mitesh; Bryce, Alan H.; Castle, Erik; Chandan, Vishal; Cheville, John; Copland, John A.; Farnell, Michael; Flotte, Thomas; Giama, Nasra; Ho, Thai; Kendrick, Michael; Kocher, Jean Pierre; Kopp, Karla; Moser, Catherine; Nagorney, David; O'Brien, Daniel; O'Neill, Brian Patrick; Patel, Tushar; Petersen, Gloria; Que, Florencia; Rivera, Michael; Roberts, Lewis; Smallridge, Robert; Smyrk, Thomas; Stanton, Melissa; Thompson, R. Houston; Torbenson, Michael; Yang, Ju Dong; Zhang, Lizhi; Brimo, Fadi; Ajani, Jaffer A.; Angulo Gonzalez, Ana Maria; Behrens, Carmen; Bondaruk, Jolanta; Broaddus, Russell; Czerniak, Bogdan; Esmaeli, Bita; Fujimoto, Junya; Gershenwald, Jeffrey; Guo, Charles; Lazar, Alexander J.; Logothetis, Christopher; Meric-Bernstam, Funda; Moran, Cesar; Ramondetta, Lois; Rice, David; Sood, Anil; Tamboli, Pheroze; Thompson, Timothy; Troncoso, Patricia; Tsao, Anne; Wistuba, Ignacio; Carter, Candace; Haydu, Lauren; Hersey, Peter; Jakrot, Valerie; Kakavand, Hojabr; Kefford, Richard; Lee, Kenneth; Long, Georgina; Mann, Graham; Quinn, Michael; Saw, Robyn; Scolyer, Richard; Shannon, Kerwin; Spillane, Andrew; Stretch, Jonathan; Synott, Maria; Thompson, John; Wilmott, James; Al-Ahmadie, Hikmat; Chan, Timothy A.; Ghossein, Ronald; Gopalan, Anuradha; Levine, Douglas A.; Reuter, Victor; Singer, Samuel; Singh, Bhuvanesh; Tien, Nguyen Viet; Broudy, Thomas; Mirsaidi, Cyrus; Nair, Praveen; Drwiega, Paul; Miller, Judy; Smith, Jennifer; Zaren, Howard; Park, Joong Won; Hung, Nguyen Phi; Kebebew, Electron; Linehan, W. Marston; Metwalli, Adam R.; Pacak, Karel; Pinto, Peter A.; Schiffman, Mark; Schmidt, Laura S.; Vocke, Cathy D.; Wentzensen, Nicolas; Worrell, Robert; Yang, Hannah; Moncrieff, Marc; Goparaju, Chandra; Melamed, Jonathan; Pass, Harvey; Botnariuc, Natalia; Caraman, Irina; Cernat, Mircea; Chemencedji, Inga; Clipca, Adrian; Doruc, Serghei; Gorincioi, Ghenadie; Mura, Sergiu; Pirtac, Maria; Stancul, Irina; Tcaciuc, Diana; Albert, Monique; Alexopoulou, Iakovina; Arnaout, Angel; Bartlett, John; Engel, Jay; Gilbert, Sebastien; Parfitt, Jeremy; Sekhon, Harman; Thomas, George; Rassl, Doris M.; Rintoul, Robert C.; Bifulco, Carlo; Tamakawa, Raina; Urba, Walter; Hayward, Nicholas; Timmers, Henri; Antenucci, Anna; Facciolo, Francesco; Grazi, Gianluca; Marino, Mirella; Merola, Roberta; de Krijger, Ronald; Gimenez-Roqueplo, Anne Paule; Piché, Alain; Chevalier, Simone; McKercher, Ginette; Birsoy, Kivanc; Barnett, Gene; Brewer, Cathy; Farver, Carol; Naska, Theresa; Pennell, Nathan A.; Raymond, Daniel; Schilero, Cathy; Smolenski, Kathy; Williams, Felicia; Morrison, Carl; Borgia, Jeffrey A.; Liptay, Michael J.; Pool, Mark; Seder, Christopher W.; Junker, Kerstin; Omberg, Larsson; Dinkin, Mikhail; Manikhas, George; Alvaro, Domenico; Bragazzi, Maria Consiglia; Cardinale, Vincenzo; Carpino, Guido; Gaudio, Eugenio; Chesla, David; Cottingham, Sandra; Dubina, Michael; Moiseenko, Fedor; Dhanasekaran, Renumathy; Becker, Karl Friedrich; Janssen, Klaus Peter; Slotta-Huspenina, Julia; Abdel-Rahman, Mohamed H.; Aziz, Dina; Bell, Sue; Cebulla, Colleen M.; Davis, Amy; Duell, Rebecca; Elder, J. Bradley; Hilty, Joe; Kumar, Bahavna; Lang, James; Lehman, Norman L.; Mandt, Randy; Nguyen, Phuong; Pilarski, Robert; Rai, Karan; Schoenfield, Lynn; Senecal, Kelly; Wakely, Paul; Hansen, Paul; Lechan, Ronald; Powers, James; Tischler, Arthur; Grizzle, William E.; Sexton, Katherine C.; Kastl, Alison; Henderson, Joel; Porten, Sima; Waldmann, Jens; Fassnacht, Martin; Asa, Sylvia L.; Schadendorf, Dirk; Couce, Marta; Graefen, Markus; Huland, Hartwig; Sauter, Guido; Schlomm, Thorsten; Simon, Ronald; Tennstedt, Pierre; Olabode, Oluwole; Nelson, Mark; Bathe, Oliver; Carroll, Peter R.; Chan, June M.; Disaia, Philip; Glenn, Pat; Kelley, Robin K.; Landen, Charles N.; Phillips, Joanna; Prados, Michael; Simko, Jeffry; Smith-McCune, Karen; VandenBerg, Scott; Roggin, Kevin; Fehrenbach, Ashley; Kendler, Ady; Sifri, Suzanne; Steele, Ruth; Jimeno, Antonio; Carey, Francis; Forgie, Ian; Mannelli, Massimo; Carney, Michael; Hernandez, Brenda; Campos, Benito; Herold-Mende, Christel; Jungk, Christin; Unterberg, Andreas; von Deimling, Andreas; Bossler, Aaron; Galbraith, Joseph; Jacobus, Laura; Knudson, Michael; Knutson, Tina; Ma, Deqin; Milhem, Mohammed; Sigmund, Rita; Godwin, Andrew K.; Madan, Rashna; Rosenthal, Howard G.; Adebamowo, Clement; Adebamowo, Sally N.; Boussioutas, Alex; Beer, David; Giordano, Thomas; Mes-Masson, Anne Marie; Saad, Fred; Bocklage, Therese; Landrum, Lisa; Mannel, Robert; Moore, Kathleen; Moxley, Katherine; Postier, Russel; Walker, Joan; Zuna, Rosemary; Feldman, Michael; Valdivieso, Federico; Dhir, Rajiv; Luketich, James; Mora Pinero, Edna M.; Quintero-Aguilo, Mario; Carlotti, Carlos Gilberto; Dos Santos, Jose Sebastião; Kemp, Rafael; Sankarankuty, Ajith; Tirapelli, Daniela; Catto, James; Agnew, Kathy; Swisher, Elizabeth; Creaney, Jenette; Robinson, Bruce; Shelley, Carl Simon; Godwin, Eryn M.; Kendall, Sara; Shipman, Cassaundra; Bradford, Carol; Carey, Thomas; Haddad, Andrea; Moyer, Jeffey; Peterson, Lisa; Prince, Mark; Rozek, Laura; Wolf, Gregory; Bowman, Rayleen; Fong, Kwun M.; Yang, Ian; Korst, Robert; Rathmell, W. Kimryn; Fantacone-Campbell, J. Leigh; Hooke, Jeffrey A.; Kovatich, Albert J.; Shriver, Craig D.; DiPersio, John; Drake, Bettina; Govindan, Ramaswamy; Heath, Sharon; Ley, Timothy; Van Tine, Brian; Westervelt, Peter; Rubin, Mark A.; Lee, Jung Il; Aredes, Natália D.; Mariamidze, Armaz

2018-01-01

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic

Singapore Cancer Network (SCAN) Guidelines for Systemic Therapy of Pancreatic Adenocarcinoma.

Science.gov (United States)

2015-10-01

The SCAN pancreatic cancer workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore. The workgroup utilised a modified ADAPTE process to calibrate high quality international evidence-based clinical practice guidelines to our local setting. Five international guidelines were evaluated- those developed by the National Cancer Comprehensive Network (2014), the European Society of Medical Oncology (2012), Cancer Care Ontario (2013), the Japan Pancreas Society (2013) and the British Society of Gastroenterology, Pancreatic Society of Great Britain and Ireland, and the Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (2005). Recommendations on the management of resected, borderline resectable, locally advanced and metastatic pancreatic adenocarcinoma were developed. These adapted guidelines form the SCAN Guidelines for systemic therapy for pancreatic adenocarcinoma in Singapore.

Characterization of the Usage of the Serine Metabolic Network in Human Cancer

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Mahya Mehrmohamadi

2014-11-01

Full Text Available The serine, glycine, one-carbon (SGOC metabolic network is implicated in cancer pathogenesis, but its general functions are unknown. We carried out a computational reconstruction of the SGOC network and then characterized its expression across thousands of cancer tissues. Pathways including methylation and redox metabolism exhibited heterogeneous expression indicating a strong context dependency of their usage in tumors. From an analysis of coexpression, simultaneous up- or downregulation of nucleotide synthesis, NADPH, and glutathione synthesis was found to be a common occurrence in all cancers. Finally, we developed a method to trace the metabolic fate of serine using stable isotopes, high-resolution mass spectrometry, and a mathematical model. Although the expression of single genes didn’t appear indicative of flux, the collective expression of several genes in a given pathway allowed for successful flux prediction. Altogether, these findings identify expansive and heterogeneous functions for the SGOC metabolic network in human cancer.

Endogenous molecular network reveals two mechanisms of heterogeneity within gastric cancer

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Li, Site; Zhu, Xiaomei; Liu, Bingya; Wang, Gaowei; Ao, Ping

2015-01-01

Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and research. Gastric cancer (GC) cells have generally been classified into two heterogeneous cellular phenotypes, the gastric and intestinal types, yet the mechanisms of maintaining two phenotypes and controlling phenotypic transition are largely unknown. A qualitative systematic framework, the endogenous molecular network hypothesis, has recently been proposed to understand cancer genesis and progression. Here, a minimal network corresponding to such framework was found for GC and was quantified via a stochastic nonlinear dynamical system. We then further extended the framework to address the important question of intratumor heterogeneity quantitatively. The working network characterized main known features of normal gastric epithelial and GC cell phenotypes. Our results demonstrated that four positive feedback loops in the network are critical for GC cell phenotypes. Moreover, two mechanisms that contribute to GC cell heterogeneity were identified: particular positive feedback loops are responsible for the maintenance of intestinal and gastric phenotypes; GC cell progression routes that were revealed by the dynamical behaviors of individual key components are heterogeneous. In this work, we constructed an endogenous molecular network of GC that can be expanded in the future and would broaden the known mechanisms of intratumor heterogeneity. PMID:25962957

Network analysis of microRNAs and their regulation in human ovarian cancer

KAUST Repository

Schmeier, Sebastian

2011-11-03

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that repress the translation of messenger RNAs (mRNAs) or degrade mRNAs. These functions of miRNAs allow them to control key cellular processes such as development, differentiation and apoptosis, and they have also been implicated in several cancers such as leukaemia, lung, pancreatic and ovarian cancer (OC). Unfortunately, the specific machinery of miRNA regulation, involving transcription factors (TFs) and transcription co-factors (TcoFs), is not well understood. In the present study we focus on computationally deciphering the underlying network of miRNAs, their targets, and their control mechanisms that have an influence on OC development.Results: We analysed experimentally verified data from multiple sources that describe miRNA influence on diseases, miRNA targeting of mRNAs, and on protein-protein interactions, and combined this data with ab initio transcription factor binding site predictions within miRNA promoter regions. From these analyses, we derived a network that describes the influence of miRNAs and their regulation in human OC. We developed a methodology to analyse the network in order to find the nodes that have the largest potential of influencing the network\\'s behaviour (network hubs). We further show the potentially most influential miRNAs, TFs and TcoFs, showing subnetworks illustrating the involved mechanisms as well as regulatory miRNA network motifs in OC. We find an enrichment of miRNA targeted OC genes in the highly relevant pathways cell cycle regulation and apoptosis.Conclusions: We combined several sources of interaction and association data to analyse and place miRNAs within regulatory pathways that influence human OC. These results represent the first comprehensive miRNA regulatory network analysis for human OC. This suggests that miRNAs and their regulation may play a major role in OC and that further directed research in this area is of utmost importance to enhance

Integrative gene network construction to analyze cancer recurrence using semi-supervised learning.

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Park, Chihyun; Ahn, Jaegyoon; Kim, Hyunjin; Park, Sanghyun

2014-01-01

The prognosis of cancer recurrence is an important research area in bioinformatics and is challenging due to the small sample sizes compared to the vast number of genes. There have been several attempts to predict cancer recurrence. Most studies employed a supervised approach, which uses only a few labeled samples. Semi-supervised learning can be a great alternative to solve this problem. There have been few attempts based on manifold assumptions to reveal the detailed roles of identified cancer genes in recurrence. In order to predict cancer recurrence, we proposed a novel semi-supervised learning algorithm based on a graph regularization approach. We transformed the gene expression data into a graph structure for semi-supervised learning and integrated protein interaction data with the gene expression data to select functionally-related gene pairs. Then, we predicted the recurrence of cancer by applying a regularization approach to the constructed graph containing both labeled and unlabeled nodes. The average improvement rate of accuracy for three different cancer datasets was 24.9% compared to existing supervised and semi-supervised methods. We performed functional enrichment on the gene networks used for learning. We identified that those gene networks are significantly associated with cancer-recurrence-related biological functions. Our algorithm was developed with standard C++ and is available in Linux and MS Windows formats in the STL library. The executable program is freely available at: http://embio.yonsei.ac.kr/~Park/ssl.php.

Integrative gene network construction to analyze cancer recurrence using semi-supervised learning.

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Chihyun Park

Full Text Available BACKGROUND: The prognosis of cancer recurrence is an important research area in bioinformatics and is challenging due to the small sample sizes compared to the vast number of genes. There have been several attempts to predict cancer recurrence. Most studies employed a supervised approach, which uses only a few labeled samples. Semi-supervised learning can be a great alternative to solve this problem. There have been few attempts based on manifold assumptions to reveal the detailed roles of identified cancer genes in recurrence. RESULTS: In order to predict cancer recurrence, we proposed a novel semi-supervised learning algorithm based on a graph regularization approach. We transformed the gene expression data into a graph structure for semi-supervised learning and integrated protein interaction data with the gene expression data to select functionally-related gene pairs. Then, we predicted the recurrence of cancer by applying a regularization approach to the constructed graph containing both labeled and unlabeled nodes. CONCLUSIONS: The average improvement rate of accuracy for three different cancer datasets was 24.9% compared to existing supervised and semi-supervised methods. We performed functional enrichment on the gene networks used for learning. We identified that those gene networks are significantly associated with cancer-recurrence-related biological functions. Our algorithm was developed with standard C++ and is available in Linux and MS Windows formats in the STL library. The executable program is freely available at: http://embio.yonsei.ac.kr/~Park/ssl.php.

Network analysis of microRNAs and their regulation in human ovarian cancer

KAUST Repository

Schmeier, Sebastian; Schaefer, Ulf; Essack, Magbubah; Bajic, Vladimir B.

2011-01-01

Background: MicroRNAs (miRNAs) are small non-coding RNA molecules that repress the translation of messenger RNAs (mRNAs) or degrade mRNAs. These functions of miRNAs allow them to control key cellular processes such as development, differentiation and apoptosis, and they have also been implicated in several cancers such as leukaemia, lung, pancreatic and ovarian cancer (OC). Unfortunately, the specific machinery of miRNA regulation, involving transcription factors (TFs) and transcription co-factors (TcoFs), is not well understood. In the present study we focus on computationally deciphering the underlying network of miRNAs, their targets, and their control mechanisms that have an influence on OC development.Results: We analysed experimentally verified data from multiple sources that describe miRNA influence on diseases, miRNA targeting of mRNAs, and on protein-protein interactions, and combined this data with ab initio transcription factor binding site predictions within miRNA promoter regions. From these analyses, we derived a network that describes the influence of miRNAs and their regulation in human OC. We developed a methodology to analyse the network in order to find the nodes that have the largest potential of influencing the network's behaviour (network hubs). We further show the potentially most influential miRNAs, TFs and TcoFs, showing subnetworks illustrating the involved mechanisms as well as regulatory miRNA network motifs in OC. We find an enrichment of miRNA targeted OC genes in the highly relevant pathways cell cycle regulation and apoptosis.Conclusions: We combined several sources of interaction and association data to analyse and place miRNAs within regulatory pathways that influence human OC. These results represent the first comprehensive miRNA regulatory network analysis for human OC. This suggests that miRNAs and their regulation may play a major role in OC and that further directed research in this area is of utmost importance to enhance our

The meaning and validation of social support networks for close family of persons with advanced cancer

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Sjolander Catarina

2012-09-01

Full Text Available Abstract Background To strengthen the mental well-being of close family of persons newly diagnosed as having cancer, it is necessary to acquire a greater understanding of their experiences of social support networks, so as to better assess what resources are available to them from such networks and what professional measures are required. The main aim of the present study was to explore the meaning of these networks for close family of adult persons in the early stage of treatment for advanced lung or gastrointestinal cancer. An additional aim was to validate the study’s empirical findings by means of the Finfgeld-Connett conceptual model for social support. The intention was to investigate whether these findings were in accordance with previous research in nursing. Methods Seventeen family members with a relative who 8–14 weeks earlier had been diagnosed as having lung or gastrointestinal cancer were interviewed. The data were subjected to qualitative latent content analysis and validated by means of identifying antecedents and critical attributes. Results The meaning or main attribute of the social support network was expressed by the theme Confirmation through togetherness, based on six subthemes covering emotional and, to a lesser extent, instrumental support. Confirmation through togetherness derived principally from information, understanding, encouragement, involvement and spiritual community. Three subthemes were identified as the antecedents to social support: Need of support, Desire for a deeper relationship with relatives, Network to turn to. Social support involves reciprocal exchange of verbal and non-verbal information provided mainly by lay persons. Conclusions The study provides knowledge of the antecedents and attributes of social support networks, particularly from the perspective of close family of adult persons with advanced lung or gastrointestinal cancer. There is a need for measurement instruments that could

NetNorM: Capturing cancer-relevant information in somatic exome mutation data with gene networks for cancer stratification and prognosis.

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Le Morvan, Marine; Zinovyev, Andrei; Vert, Jean-Philippe

2017-06-01

Genome-wide somatic mutation profiles of tumours can now be assessed efficiently and promise to move precision medicine forward. Statistical analysis of mutation profiles is however challenging due to the low frequency of most mutations, the varying mutation rates across tumours, and the presence of a majority of passenger events that hide the contribution of driver events. Here we propose a method, NetNorM, to represent whole-exome somatic mutation data in a form that enhances cancer-relevant information using a gene network as background knowledge. We evaluate its relevance for two tasks: survival prediction and unsupervised patient stratification. Using data from 8 cancer types from The Cancer Genome Atlas (TCGA), we show that it improves over the raw binary mutation data and network diffusion for these two tasks. In doing so, we also provide a thorough assessment of somatic mutations prognostic power which has been overlooked by previous studies because of the sparse and binary nature of mutations.

A Network Pharmacology Approach to Uncover the Multiple Mechanisms of Hedyotis diffusa Willd. on Colorectal Cancer

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Xinkui Liu

2018-01-01

Full Text Available Background. As one of the most frequently diagnosed cancer diseases globally, colorectal cancer (CRC remains an important cause of cancer-related death. Although the traditional Chinese herb Hedyotis diffusa Willd. (HDW has been proven to be effective for treating CRC in clinical practice, its definite mechanisms have not been completely deciphered. Objective. The aim of our research is to systematically explore the multiple mechanisms of HDW on CRC. Methods. This study adopted the network pharmacology approach, which was mainly composed of active component gathering, target prediction, CRC gene collection, network analysis, and gene enrichment analysis. Results. The network analysis showed that 10 targets might be the therapeutic targets of HDW on CRC, namely, HRAS, PIK3CA, KRAS, TP53, APC, BRAF, GSK3B, CDK2, AKT1, and RAF1. The gene enrichment analysis implied that HDW probably benefits patients with CRC by modulating pathways related to cancers, infectious diseases, endocrine system, immune system, nervous system, signal transduction, cellular community, and cell motility. Conclusions. This study partially verified and predicted the pharmacological and molecular mechanism of HDW against CRC from a holistic perspective, which will also lay a foundation for the further experimental research and clinical rational application of HDW.

Prediction of Bladder Cancer Recurrences Using Artificial Neural Networks

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Zulueta Guerrero, Ekaitz; Garay, Naiara Telleria; Lopez-Guede, Jose Manuel; Vilches, Borja Ayerdi; Iragorri, Eider Egilegor; Castaños, David Lecumberri; de La Hoz Rastrollo, Ana Belén; Peña, Carlos Pertusa

Even if considerable advances have been made in the field of early diagnosis, there is no simple, cheap and non-invasive method that can be applied to the clinical monitorisation of bladder cancer patients. Moreover, bladder cancer recurrences or the reappearance of the tumour after its surgical resection cannot be predicted in the current clinical setting. In this study, Artificial Neural Networks (ANN) were used to assess how different combinations of classical clinical parameters (stage-grade and age) and two urinary markers (growth factor and pro-inflammatory mediator) could predict post surgical recurrences in bladder cancer patients. Different ANN methods, input parameter combinations and recurrence related output variables were used and the resulting positive and negative prediction rates compared. MultiLayer Perceptron (MLP) was selected as the most predictive model and urinary markers showed the highest sensitivity, predicting correctly 50% of the patients that would recur in a 2 year follow-up period.

Deregulation of an imprinted gene network in prostate cancer.

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Ribarska, Teodora; Goering, Wolfgang; Droop, Johanna; Bastian, Klaus-Marius; Ingenwerth, Marc; Schulz, Wolfgang A

2014-05-01

Multiple epigenetic alterations contribute to prostate cancer progression by deregulating gene expression. Epigenetic mechanisms, especially differential DNA methylation at imprinting control regions (termed DMRs), normally ensure the exclusive expression of imprinted genes from one specific parental allele. We therefore wondered to which extent imprinted genes become deregulated in prostate cancer and, if so, whether deregulation is due to altered DNA methylation at DMRs. Therefore, we selected presumptive deregulated imprinted genes from a previously conducted in silico analysis and from the literature and analyzed their expression in prostate cancer tissues by qRT-PCR. We found significantly diminished expression of PLAGL1/ZAC1, MEG3, NDN, CDKN1C, IGF2, and H19, while LIT1 was significantly overexpressed. The PPP1R9A gene, which is imprinted in selected tissues only, was strongly overexpressed, but was expressed biallelically in benign and cancerous prostatic tissues. Expression of many of these genes was strongly correlated, suggesting co-regulation, as in an imprinted gene network (IGN) reported in mice. Deregulation of the network genes also correlated with EZH2 and HOXC6 overexpression. Pyrosequencing analysis of all relevant DMRs revealed generally stable DNA methylation between benign and cancerous prostatic tissues, but frequent hypo- and hyper-methylation was observed at the H19 DMR in both benign and cancerous tissues. Re-expression of the ZAC1 transcription factor induced H19, CDKN1C and IGF2, supporting its function as a nodal regulator of the IGN. Our results indicate that a group of imprinted genes are coordinately deregulated in prostate cancers, independently of DNA methylation changes.

The role of organizational affiliations and research networks in the diffusion of breast cancer treatment innovation.

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Carpenter, William R; Reeder-Hayes, Katherine; Bainbridge, John; Meyer, Anne-Marie; Amos, Keith D; Weiner, Bryan J; Godley, Paul A

2011-02-01

The National Institutes of Health (NIH) sees provider-based research networks and other organizational linkages between academic researchers and community practitioners as promising vehicles for accelerating the translation of research into practice. This study examines whether organizational research affiliations and teaching affiliations are associated with accelerated diffusion of sentinel lymph node biopsy (SLNB), an innovation in the treatment of early-stage breast cancer. Surveillance Epidemiology and End Results-Medicare data were used to examine the diffusion of SLNB for treatment of early-stage breast cancer among women aged 65 years and older diagnosed between 2000 and 2002, shortly after Medicare approved and began reimbursing for the procedure. In this population, patients treated at an organization affiliated with a research network--the American College of Surgeons Oncology Group (ACOSOG) or other National Cancer Institute (NCI) cooperative groups--were more likely to receive the innovative treatment (SLNB) than patients treated at unaffiliated organizations (odds ratio: 2.70, 95% confidence interval: 1.77-4.12; odds ratio: 1.84, 95% confidence interval: 1.26-2.69, respectively). Neither hospital teaching status nor surgical volume was significantly associated with differences in SLNB use. Patients who receive cancer treatment at organizations affiliated with cancer research networks have an enhanced probability of receiving SLNB, an innovative procedure that offers the promise of improved patient outcomes. Study findings support the NIH Roadmap and programs such as the NCI's Community Clinical Oncology Program, as they seek to accelerate the translation of research into practice by simultaneously accelerating and broadening cancer research in the community.

Inference of hierarchical regulatory network of estrogen-dependent breast cancer through ChIP-based data

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Parvin Jeffrey

2010-12-01

Full Text Available Abstract Background Global profiling of in vivo protein-DNA interactions using ChIP-based technologies has evolved rapidly in recent years. Although many genome-wide studies have identified thousands of ERα binding sites and have revealed the associated transcription factor (TF partners, such as AP1, FOXA1 and CEBP, little is known about ERα associated hierarchical transcriptional regulatory networks. Results In this study, we applied computational approaches to analyze three public available ChIP-based datasets: ChIP-seq, ChIP-PET and ChIP-chip, and to investigate the hierarchical regulatory network for ERα and ERα partner TFs regulation in estrogen-dependent breast cancer MCF7 cells. 16 common TFs and two common new TF partners (RORA and PITX2 were found among ChIP-seq, ChIP-chip and ChIP-PET datasets. The regulatory networks were constructed by scanning the ChIP-peak region with TF specific position weight matrix (PWM. A permutation test was performed to test the reliability of each connection of the network. We then used DREM software to perform gene ontology function analysis on the common genes. We found that FOS, PITX2, RORA and FOXA1 were involved in the up-regulated genes. We also conducted the ERα and Pol-II ChIP-seq experiments in tamoxifen resistance MCF7 cells (denoted as MCF7-T in this study and compared the difference between MCF7 and MCF7-T cells. The result showed very little overlap between these two cells in terms of targeted genes (21.2% of common genes and targeted TFs (25% of common TFs. The significant dissimilarity may indicate totally different transcriptional regulatory mechanisms between these two cancer cells. Conclusions Our study uncovers new estrogen-mediated regulatory networks by mining three ChIP-based data in MCF7 cells and ChIP-seq data in MCF7-T cells. We compared the different ChIP-based technologies as well as different breast cancer cells. Our computational analytical approach may guide biologists to

A comparative study of breast cancer diagnosis based on neural network ensemble via improved training algorithms.

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Azami, Hamed; Escudero, Javier

2015-08-01

Breast cancer is one of the most common types of cancer in women all over the world. Early diagnosis of this kind of cancer can significantly increase the chances of long-term survival. Since diagnosis of breast cancer is a complex problem, neural network (NN) approaches have been used as a promising solution. Considering the low speed of the back-propagation (BP) algorithm to train a feed-forward NN, we consider a number of improved NN trainings for the Wisconsin breast cancer dataset: BP with momentum, BP with adaptive learning rate, BP with adaptive learning rate and momentum, Polak-Ribikre conjugate gradient algorithm (CGA), Fletcher-Reeves CGA, Powell-Beale CGA, scaled CGA, resilient BP (RBP), one-step secant and quasi-Newton methods. An NN ensemble, which is a learning paradigm to combine a number of NN outputs, is used to improve the accuracy of the classification task. Results demonstrate that NN ensemble-based classification methods have better performance than NN-based algorithms. The highest overall average accuracy is 97.68% obtained by NN ensemble trained by RBP for 50%-50% training-test evaluation method.

Network-Based Integration of Disparate Omic Data To Identify "Silent Players" in Cancer.

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Matthew Ruffalo

2015-12-01

Full Text Available Development of high-throughput monitoring technologies enables interrogation of cancer samples at various levels of cellular activity. Capitalizing on these developments, various public efforts such as The Cancer Genome Atlas (TCGA generate disparate omic data for large patient cohorts. As demonstrated by recent studies, these heterogeneous data sources provide the opportunity to gain insights into the molecular changes that drive cancer pathogenesis and progression. However, these insights are limited by the vast search space and as a result low statistical power to make new discoveries. In this paper, we propose methods for integrating disparate omic data using molecular interaction networks, with a view to gaining mechanistic insights into the relationship between molecular changes at different levels of cellular activity. Namely, we hypothesize that genes that play a role in cancer development and progression may be implicated by neither frequent mutation nor differential expression, and that network-based integration of mutation and differential expression data can reveal these "silent players". For this purpose, we utilize network-propagation algorithms to simulate the information flow in the cell at a sample-specific resolution. We then use the propagated mutation and expression signals to identify genes that are not necessarily mutated or differentially expressed genes, but have an essential role in tumor development and patient outcome. We test the proposed method on breast cancer and glioblastoma multiforme data obtained from TCGA. Our results show that the proposed method can identify important proteins that are not readily revealed by molecular data, providing insights beyond what can be gleaned by analyzing different types of molecular data in isolation.

Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype

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da Silveira, W A; Palma, P V B; Sicchieri, R D

2017-01-01

Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis...... of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies....... and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression...

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

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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

VarWalker: personalized mutation network analysis of putative cancer genes from next-generation sequencing data.

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Jia, Peilin; Zhao, Zhongming

2014-02-01

A major challenge in interpreting the large volume of mutation data identified by next-generation sequencing (NGS) is to distinguish driver mutations from neutral passenger mutations to facilitate the identification of targetable genes and new drugs. Current approaches are primarily based on mutation frequencies of single-genes, which lack the power to detect infrequently mutated driver genes and ignore functional interconnection and regulation among cancer genes. We propose a novel mutation network method, VarWalker, to prioritize driver genes in large scale cancer mutation data. VarWalker fits generalized additive models for each sample based on sample-specific mutation profiles and builds on the joint frequency of both mutation genes and their close interactors. These interactors are selected and optimized using the Random Walk with Restart algorithm in a protein-protein interaction network. We applied the method in >300 tumor genomes in two large-scale NGS benchmark datasets: 183 lung adenocarcinoma samples and 121 melanoma samples. In each cancer, we derived a consensus mutation subnetwork containing significantly enriched consensus cancer genes and cancer-related functional pathways. These cancer-specific mutation networks were then validated using independent datasets for each cancer. Importantly, VarWalker prioritizes well-known, infrequently mutated genes, which are shown to interact with highly recurrently mutated genes yet have been ignored by conventional single-gene-based approaches. Utilizing VarWalker, we demonstrated that network-assisted approaches can be effectively adapted to facilitate the detection of cancer driver genes in NGS data.

Integrative modelling of the influence of MAPK network on cancer cell fate decision.

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Luca Grieco

2013-10-01

Full Text Available The Mitogen-Activated Protein Kinase (MAPK network consists of tightly interconnected signalling pathways involved in diverse cellular processes, such as cell cycle, survival, apoptosis and differentiation. Although several studies reported the involvement of these signalling cascades in cancer deregulations, the precise mechanisms underlying their influence on the balance between cell proliferation and cell death (cell fate decision in pathological circumstances remain elusive. Based on an extensive analysis of published data, we have built a comprehensive and generic reaction map for the MAPK signalling network, using CellDesigner software. In order to explore the MAPK responses to different stimuli and better understand their contributions to cell fate decision, we have considered the most crucial components and interactions and encoded them into a logical model, using the software GINsim. Our logical model analysis particularly focuses on urinary bladder cancer, where MAPK network deregulations have often been associated with specific phenotypes. To cope with the combinatorial explosion of the number of states, we have applied novel algorithms for model reduction and for the compression of state transition graphs, both implemented into the software GINsim. The results of systematic simulations for different signal combinations and network perturbations were found globally coherent with published data. In silico experiments further enabled us to delineate the roles of specific components, cross-talks and regulatory feedbacks in cell fate decision. Finally, tentative proliferative or anti-proliferative mechanisms can be connected with established bladder cancer deregulations, namely Epidermal Growth Factor Receptor (EGFR over-expression and Fibroblast Growth Factor Receptor 3 (FGFR3 activating mutations.

A network-based drug repositioning infrastructure for precision cancer medicine through targeting significantly mutated genes in the human cancer genomes.

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Cheng, Feixiong; Zhao, Junfei; Fooksa, Michaela; Zhao, Zhongming

2016-07-01

Development of computational approaches and tools to effectively integrate multidomain data is urgently needed for the development of newly targeted cancer therapeutics. We proposed an integrative network-based infrastructure to identify new druggable targets and anticancer indications for existing drugs through targeting significantly mutated genes (SMGs) discovered in the human cancer genomes. The underlying assumption is that a drug would have a high potential for anticancer indication if its up-/down-regulated genes from the Connectivity Map tended to be SMGs or their neighbors in the human protein interaction network. We assembled and curated 693 SMGs in 29 cancer types and found 121 proteins currently targeted by known anticancer or noncancer (repurposed) drugs. We found that the approved or experimental cancer drugs could potentially target these SMGs in 33.3% of the mutated cancer samples, and this number increased to 68.0% by drug repositioning through surveying exome-sequencing data in approximately 5000 normal-tumor pairs from The Cancer Genome Atlas. Furthermore, we identified 284 potential new indications connecting 28 cancer types and 48 existing drugs (adjusted P < .05), with a 66.7% success rate validated by literature data. Several existing drugs (e.g., niclosamide, valproic acid, captopril, and resveratrol) were predicted to have potential indications for multiple cancer types. Finally, we used integrative analysis to showcase a potential mechanism-of-action for resveratrol in breast and lung cancer treatment whereby it targets several SMGs (ARNTL, ASPM, CTTN, EIF4G1, FOXP1, and STIP1). In summary, we demonstrated that our integrative network-based infrastructure is a promising strategy to identify potential druggable targets and uncover new indications for existing drugs to speed up molecularly targeted cancer therapeutics. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All

Kinome-wide Decoding of Network-Attacking Mutations Rewiring Cancer Signaling

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Creixell, Pau; Schoof, Erwin M; Simpson, Craig D.

2015-01-01

Cancer cells acquire pathological phenotypes through accumulation of mutations that perturb signaling networks. However, global analysis of these events is currently limited. Here, we identify six types of network-attacking mutations (NAMs), including changes in kinase and SH2 modulation, network...... and experimentally validated several NAMs, including PKCγ M501I and PKD1 D665N, which encode specificity switches analogous to the appearance of kinases de novo within the kinome. We discover mutant molecular logic gates, a drift toward phospho-threonine signaling, weakening of phosphorylation motifs, and kinase...

Predictive genomics: a cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data.

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Wang, Edwin; Zaman, Naif; Mcgee, Shauna; Milanese, Jean-Sébastien; Masoudi-Nejad, Ali; O'Connor-McCourt, Maureen

2015-02-01

Tumor genome sequencing leads to documenting thousands of DNA mutations and other genomic alterations. At present, these data cannot be analyzed adequately to aid in the understanding of tumorigenesis and its evolution. Moreover, we have little insight into how to use these data to predict clinical phenotypes and tumor progression to better design patient treatment. To meet these challenges, we discuss a cancer hallmark network framework for modeling genome sequencing data to predict cancer clonal evolution and associated clinical phenotypes. The framework includes: (1) cancer hallmarks that can be represented by a few molecular/signaling networks. 'Network operational signatures' which represent gene regulatory logics/strengths enable to quantify state transitions and measures of hallmark traits. Thus, sets of genomic alterations which are associated with network operational signatures could be linked to the state/measure of hallmark traits. The network operational signature transforms genotypic data (i.e., genomic alterations) to regulatory phenotypic profiles (i.e., regulatory logics/strengths), to cellular phenotypic profiles (i.e., hallmark traits) which lead to clinical phenotypic profiles (i.e., a collection of hallmark traits). Furthermore, the framework considers regulatory logics of the hallmark networks under tumor evolutionary dynamics and therefore also includes: (2) a self-promoting positive feedback loop that is dominated by a genomic instability network and a cell survival/proliferation network is the main driver of tumor clonal evolution. Surrounding tumor stroma and its host immune systems shape the evolutionary paths; (3) cell motility initiating metastasis is a byproduct of the above self-promoting loop activity during tumorigenesis; (4) an emerging hallmark network which triggers genome duplication dominates a feed-forward loop which in turn could act as a rate-limiting step for tumor formation; (5) mutations and other genomic alterations have

Social Networking Site Usage Among Childhood Cancer Survivors - A Potential Tool for Research Recruitment?

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Seltzer, Erica D.; Stolley, Melinda R.; Mensah, Edward K.; Sharp, Lisa K.

2014-01-01

Purpose The recent and rapid growth of social networking site (SNS) use presents a unique public health opportunity to develop effective strategies for the recruitment of hard-to-reach participants for cancer research studies. This survey investigated childhood cancer survivors’ reported use of SNS such as facebook or MySpace and their perceptions of using SNS, for recruitment into survivorship research. Methods Sixty White, Black and Hispanic, adult childhood cancer survivors (range 18 – 48 years of age) that were randomly selected from a larger childhood cancer study, the Chicago Healthy Living Study (CHLS), participated in this pilot survey. Telephone surveys were conducted to understand current SNS activity and attitudes towards using SNS as a cancer research recruitment tool. Results Seventy percent of participants reported SNS usage of which 80% were at least weekly users and 79 % reported positive attitudes towards the use of SNS as a recruitment tool for survivorship research. Conclusions and implications for cancer survivors The results of this pilot study revealed that SNS use was high and regular among the childhood cancer survivors sampled. Most had positive attitudes towards using SNS for recruitment of research. The results of this pilot survey suggest that SNS may offer an alternative approach for recruitment of childhood cancer survivors into research. PMID:24532046

Physician social networks and variation in prostate cancer treatment in three cities.

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Pollack, Craig Evan; Weissman, Gary; Bekelman, Justin; Liao, Kaijun; Armstrong, Katrina

2012-02-01

To examine whether physician social networks are associated with variation in treatment for men with localized prostate cancer. 2004-2005 Surveillance, Epidemiology and End Results-Medicare data from three cities. We identified the physicians who care for patients with prostate cancer and created physician networks for each city based on shared patients. Subgroups of urologists were defined as physicians with dense connections with one another via shared patients. Subgroups varied widely in their unadjusted rates of prostatectomy and the racial/ethnic and socioeconomic composition of their patients. There was an association between urologist subgroup and receipt of prostatectomy. In city A, four subgroups had significantly lower odds of prostatectomy compared with the subgroup with the highest rates of prostatectomy after adjusting for patient clinical and sociodemographic characteristics. Similarly, in cities B and C, subgroups had significantly lower odds of prostatectomy compared with the baseline. Using claims data to identify physician networks may provide an insight into the observed variation in treatment patterns for men with prostate cancer. © Health Research and Educational Trust.

Rough set soft computing cancer classification and network: one stone, two birds.

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Zhang, Yue

2010-07-15

Gene expression profiling provides tremendous information to help unravel the complexity of cancer. The selection of the most informative genes from huge noise for cancer classification has taken centre stage, along with predicting the function of such identified genes and the construction of direct gene regulatory networks at different system levels with a tuneable parameter. A new study by Wang and Gotoh described a novel Variable Precision Rough Sets-rooted robust soft computing method to successfully address these problems and has yielded some new insights. The significance of this progress and its perspectives will be discussed in this article.

Construction and analysis of lncRNA-lncRNA synergistic networks to reveal clinically relevant lncRNAs in cancer.

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Li, Yongsheng; Chen, Juan; Zhang, Jinwen; Wang, Zishan; Shao, Tingting; Jiang, Chunjie; Xu, Juan; Li, Xia

2015-09-22

Long non-coding RNAs (lncRNAs) play key roles in diverse biological processes. Moreover, the development and progression of cancer often involves the combined actions of several lncRNAs. Here we propose a multi-step method for constructing lncRNA-lncRNA functional synergistic networks (LFSNs) through co-regulation of functional modules having three features: common coexpressed genes of lncRNA pairs, enrichment in the same functional category and close proximity within protein interaction networks. Applied to three cancers, we constructed cancer-specific LFSNs and found that they exhibit a scale free and modular architecture. In addition, cancer-associated lncRNAs tend to be hubs and are enriched within modules. Although there is little synergistic pairing of lncRNAs across cancers, lncRNA pairs involved in the same cancer hallmarks by regulating same or different biological processes. Finally, we identify prognostic biomarkers within cancer lncRNA expression datasets using modules derived from LFSNs. In summary, this proof-of-principle study indicates synergistic lncRNA pairs can be identified through integrative analysis of genome-wide expression data sets and functional information.

Bayesian networks for clinical decision support in lung cancer care.

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M Berkan Sesen

Full Text Available Survival prediction and treatment selection in lung cancer care are characterised by high levels of uncertainty. Bayesian Networks (BNs, which naturally reason with uncertain domain knowledge, can be applied to aid lung cancer experts by providing personalised survival estimates and treatment selection recommendations. Based on the English Lung Cancer Database (LUCADA, we evaluate the feasibility of BNs for these two tasks, while comparing the performances of various causal discovery approaches to uncover the most feasible network structure from expert knowledge and data. We show first that the BN structure elicited from clinicians achieves a disappointing area under the ROC curve of 0.75 (± 0.03, whereas a structure learned by the CAMML hybrid causal discovery algorithm, which adheres with the temporal restrictions, achieves 0.81 (± 0.03. Second, our causal intervention results reveal that BN treatment recommendations, based on prescribing the treatment plan that maximises survival, can only predict the recorded treatment plan 29% of the time. However, this percentage rises to 76% when partial matches are included.

Targeted agents for patients with advanced/metastatic pancreatic cancer: A protocol for systematic review and network meta-analysis.

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Di, Baoshan; Pan, Bei; Ge, Long; Ma, Jichun; Wu, Yiting; Guo, Tiankang

2018-03-01

Pancreatic cancer (PC) is a devastating malignant tumor. Although surgical resection may offer a good prognosis and prolong survival, approximately 80% patients with PC are always diagnosed as unresectable tumor. National Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy as efficient treatment. While, according to recent studies, targeted agents might be a better available option for advanced or metastatic pancreatic cancer patients. The aim of this systematic review and network meta-analysis will be to examine the differences of different targeted interventions for advanced/metastatic PC patients. We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. To identify relevant studies, 6 electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) will be searched. The risk of bias in included randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook version 5.1.0. And we will use GRADE approach to assess the quality of evidence from network meta-analysis. Data will be analyzed using R 3.4.1 software. To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of different targeted agents and targeted agents plus chemotherapy for advanced/metastatic pancreatic cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required. We will disseminate the results of this review by submitting to a peer-reviewed journal.

Network-Based Isoform Quantification with RNA-Seq Data for Cancer Transcriptome Analysis.

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Wei Zhang

2015-12-01

Full Text Available High-throughput mRNA sequencing (RNA-Seq is widely used for transcript quantification of gene isoforms. Since RNA-Seq data alone is often not sufficient to accurately identify the read origins from the isoforms for quantification, we propose to explore protein domain-domain interactions as prior knowledge for integrative analysis with RNA-Seq data. We introduce a Network-based method for RNA-Seq-based Transcript Quantification (Net-RSTQ to integrate protein domain-domain interaction network with short read alignments for transcript abundance estimation. Based on our observation that the abundances of the neighboring isoforms by domain-domain interactions in the network are positively correlated, Net-RSTQ models the expression of the neighboring transcripts as Dirichlet priors on the likelihood of the observed read alignments against the transcripts in one gene. The transcript abundances of all the genes are then jointly estimated with alternating optimization of multiple EM problems. In simulation Net-RSTQ effectively improved isoform transcript quantifications when isoform co-expressions correlate with their interactions. qRT-PCR results on 25 multi-isoform genes in a stem cell line, an ovarian cancer cell line, and a breast cancer cell line also showed that Net-RSTQ estimated more consistent isoform proportions with RNA-Seq data. In the experiments on the RNA-Seq data in The Cancer Genome Atlas (TCGA, the transcript abundances estimated by Net-RSTQ are more informative for patient sample classification of ovarian cancer, breast cancer and lung cancer. All experimental results collectively support that Net-RSTQ is a promising approach for isoform quantification. Net-RSTQ toolbox is available at http://compbio.cs.umn.edu/Net-RSTQ/.

Identifying colon cancer risk modules with better classification performance based on human signaling network.

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Qu, Xiaoli; Xie, Ruiqiang; Chen, Lina; Feng, Chenchen; Zhou, Yanyan; Li, Wan; Huang, Hao; Jia, Xu; Lv, Junjie; He, Yuehan; Du, Youwen; Li, Weiguo; Shi, Yuchen; He, Weiming

2014-10-01

Identifying differences between normal and tumor samples from a modular perspective may help to improve our understanding of the mechanisms responsible for colon cancer. Many cancer studies have shown that signaling transduction and biological pathways are disturbed in disease states, and expression profiles can distinguish variations in diseases. In this study, we integrated a weighted human signaling network and gene expression profiles to select risk modules associated with tumor conditions. Risk modules as classification features by our method had a better classification performance than other methods, and one risk module for colon cancer had a good classification performance for distinguishing between normal/tumor samples and between tumor stages. All genes in the module were annotated to the biological process of positive regulation of cell proliferation, and were highly associated with colon cancer. These results suggested that these genes might be the potential risk genes for colon cancer. Copyright © 2013. Published by Elsevier Inc.

Social networking site usage among childhood cancer survivors--a potential tool for research recruitment?

Science.gov (United States)

Seltzer, Erica D; Stolley, Melinda R; Mensah, Edward K; Sharp, Lisa K

2014-09-01

The recent and rapid growth of social networking site (SNS) use presents a unique public health opportunity to develop effective strategies for the recruitment of hard-to-reach participants for cancer research studies. This survey investigated childhood cancer survivors' reported use of SNS such as Facebook or MySpace and their perceptions of using SNS, for recruitment into survivorship research. Sixty White, Black, and Hispanic adult childhood cancer survivors (range 18-48 years of age) that were randomly selected from a larger childhood cancer study, the Chicago Healthy Living Study, participated in this pilot survey. Telephone surveys were conducted to understand current SNS activity and attitudes towards using SNS as a cancer research recruitment tool. Seventy percent of participants reported SNS usage of which 80 % were at least weekly users and 79 % reported positive attitudes towards the use of SNS as a recruitment tool for survivorship research. The results of this pilot study revealed that SNS use was high and regular among the childhood cancer survivors sampled. Most had positive attitudes towards using SNS for recruitment of research. The results of this pilot survey suggest that SNS may offer an alternative approach for recruitment of childhood cancer survivors into research.

Provider-based research networks and diffusion of surgical technologies among patients with early-stage kidney cancer.

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Tan, Hung-Jui; Meyer, Anne-Marie; Kuo, Tzy-Mey; Smith, Angela B; Wheeler, Stephanie B; Carpenter, William R; Nielsen, Matthew E

2015-03-15

Provider-based research networks such as the National Cancer Institute's Community Clinical Oncology Program (CCOP) have been shown to facilitate the translation of evidence-based cancer care into clinical practice. This study compared the utilization of laparoscopy and partial nephrectomy among patients with early-stage kidney cancer according to their exposure to CCOP-affiliated providers. With linked Surveillance, Epidemiology, and End Results-Medicare data, patients with T1aN0M0 kidney cancer who had been treated with nephrectomy from 2000 to 2007 were identified. For each patient, the receipt of care from a CCOP physician or hospital and treatment with laparoscopy or partial nephrectomy were determined. Adjusted for patient characteristics (eg, age, sex, and marital status) and other organizational features (eg, community hospital and National Cancer Institute-designated cancer center), multivariate logistic regression was used to estimate the association between each surgical innovation and CCOP affiliation. During the study interval, 1578 patients (26.8%) were treated by a provider with a CCOP affiliation. Trends in the utilization of laparoscopy and partial nephrectomy remained similar between affiliated and nonaffiliated providers (P ≥ .05). With adjustments for patient characteristics, organizational features, and clustering, no association was noted between CCOP affiliation and the use of laparoscopy (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.81-1.53) or partial nephrectomy (OR, 1.04; 95% CI, 0.82-1.32) despite the more frequent receipt of these treatments in academic settings (P kidney cancer, indicating perhaps a more limited scope to provider-based research networks as they pertain to translational efforts in cancer care. © 2014 American Cancer Society.

Introduction: Cancer Gene Networks.

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Clarke, Robert

2017-01-01

Constructing, evaluating, and interpreting gene networks generally sits within the broader field of systems biology, which continues to emerge rapidly, particular with respect to its application to understanding the complexity of signaling in the context of cancer biology. For the purposes of this volume, we take a broad definition of systems biology. Considering an organism or disease within an organism as a system, systems biology is the study of the integrated and coordinated interactions of the network(s) of genes, their variants both natural and mutated (e.g., polymorphisms, rearrangements, alternate splicing, mutations), their proteins and isoforms, and the organic and inorganic molecules with which they interact, to execute the biochemical reactions (e.g., as enzymes, substrates, products) that reflect the function of that system. Central to systems biology, and perhaps the only approach that can effectively manage the complexity of such systems, is the building of quantitative multiscale predictive models. The predictions of the models can vary substantially depending on the nature of the model and its inputoutput relationships. For example, a model may predict the outcome of a specific molecular reaction(s), a cellular phenotype (e.g., alive, dead, growth arrest, proliferation, and motility), a change in the respective prevalence of cell or subpopulations, a patient or patient subgroup outcome(s). Such models necessarily require computers. Computational modeling can be thought of as using machine learning and related tools to integrate the very high dimensional data generated from modern, high throughput omics technologies including genomics (next generation sequencing), transcriptomics (gene expression microarrays; RNAseq), metabolomics and proteomics (ultra high performance liquid chromatography, mass spectrometry), and "subomic" technologies to study the kinome, methylome, and others. Mathematical modeling can be thought of as the use of ordinary

Reconstruction and signal propagation analysis of the Syk signaling network in breast cancer cells.

Directory of Open Access Journals (Sweden)

Aurélien Naldi

2017-03-01

Full Text Available The ability to build in-depth cell signaling networks from vast experimental data is a key objective of computational biology. The spleen tyrosine kinase (Syk protein, a well-characterized key player in immune cell signaling, was surprisingly first shown by our group to exhibit an onco-suppressive function in mammary epithelial cells and corroborated by many other studies, but the molecular mechanisms of this function remain largely unsolved. Based on existing proteomic data, we report here the generation of an interaction-based network of signaling pathways controlled by Syk in breast cancer cells. Pathway enrichment of the Syk targets previously identified by quantitative phospho-proteomics indicated that Syk is engaged in cell adhesion, motility, growth and death. Using the components and interactions of these pathways, we bootstrapped the reconstruction of a comprehensive network covering Syk signaling in breast cancer cells. To generate in silico hypotheses on Syk signaling propagation, we developed a method allowing to rank paths between Syk and its targets. We first annotated the network according to experimental datasets. We then combined shortest path computation with random walk processes to estimate the importance of individual interactions and selected biologically relevant pathways in the network. Molecular and cell biology experiments allowed to distinguish candidate mechanisms that underlie the impact of Syk on the regulation of cortactin and ezrin, both involved in actin-mediated cell adhesion and motility. The Syk network was further completed with the results of our biological validation experiments. The resulting Syk signaling sub-networks can be explored via an online visualization platform.

Prostate Cancer Biospecimen Cohort Study

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2017-10-01

opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of the Army...SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES...14. ABSTRACT The goal of the study is development of a Prostate Cancer Biorepository Network (PCBN) resource site with high quality and well

A sparse regulatory network of copy-number driven gene expression reveals putative breast cancer oncogenes.

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Yuan, Yinyin; Curtis, Christina; Caldas, Carlos; Markowetz, Florian

2012-01-01

Copy number aberrations are recognized to be important in cancer as they may localize to regions harboring oncogenes or tumor suppressors. Such genomic alterations mediate phenotypic changes through their impact on expression. Both cis- and transacting alterations are important since they may help to elucidate putative cancer genes. However, amidst numerous passenger genes, trans-effects are less well studied due to the computational difficulty in detecting weak and sparse signals in the data, and yet may influence multiple genes on a global scale. We propose an integrative approach to learn a sparse interaction network of DNA copy-number regions with their downstream transcriptional targets in breast cancer. With respect to goodness of fit on both simulated and real data, the performance of sparse network inference is no worse than other state-of-the-art models but with the advantage of simultaneous feature selection and efficiency. The DNA-RNA interaction network helps to distinguish copy-number driven expression alterations from those that are copy-number independent. Further, our approach yields a quantitative copy-number dependency score, which distinguishes cis- versus trans-effects. When applied to a breast cancer data set, numerous expression profiles were impacted by cis-acting copy-number alterations, including several known oncogenes such as GRB7, ERBB2, and LSM1. Several trans-acting alterations were also identified, impacting genes such as ADAM2 and BAGE, which warrant further investigation. An R package named lol is available from www.markowetzlab.org/software/lol.html.

Identifying significant genetic regulatory networks in the prostate cancer from microarray data based on transcription factor analysis and conditional independency

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Yeh Cheng-Yu

2009-12-01

Full Text Available Abstract Background Prostate cancer is a world wide leading cancer and it is characterized by its aggressive metastasis. According to the clinical heterogeneity, prostate cancer displays different stages and grades related to the aggressive metastasis disease. Although numerous studies used microarray analysis and traditional clustering method to identify the individual genes during the disease processes, the important gene regulations remain unclear. We present a computational method for inferring genetic regulatory networks from micorarray data automatically with transcription factor analysis and conditional independence testing to explore the potential significant gene regulatory networks that are correlated with cancer, tumor grade and stage in the prostate cancer. Results To deal with missing values in microarray data, we used a K-nearest-neighbors (KNN algorithm to determine the precise expression values. We applied web services technology to wrap the bioinformatics toolkits and databases to automatically extract the promoter regions of DNA sequences and predicted the transcription factors that regulate the gene expressions. We adopt the microarray datasets consists of 62 primary tumors, 41 normal prostate tissues from Stanford Microarray Database (SMD as a target dataset to evaluate our method. The predicted results showed that the possible biomarker genes related to cancer and denoted the androgen functions and processes may be in the development of the prostate cancer and promote the cell death in cell cycle. Our predicted results showed that sub-networks of genes SREBF1, STAT6 and PBX1 are strongly related to a high extent while ETS transcription factors ELK1, JUN and EGR2 are related to a low extent. Gene SLC22A3 may explain clinically the differentiation associated with the high grade cancer compared with low grade cancer. Enhancer of Zeste Homolg 2 (EZH2 regulated by RUNX1 and STAT3 is correlated to the pathological stage

Identifying significant genetic regulatory networks in the prostate cancer from microarray data based on transcription factor analysis and conditional independency.

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Yeh, Hsiang-Yuan; Cheng, Shih-Wu; Lin, Yu-Chun; Yeh, Cheng-Yu; Lin, Shih-Fang; Soo, Von-Wun

2009-12-21

Prostate cancer is a world wide leading cancer and it is characterized by its aggressive metastasis. According to the clinical heterogeneity, prostate cancer displays different stages and grades related to the aggressive metastasis disease. Although numerous studies used microarray analysis and traditional clustering method to identify the individual genes during the disease processes, the important gene regulations remain unclear. We present a computational method for inferring genetic regulatory networks from micorarray data automatically with transcription factor analysis and conditional independence testing to explore the potential significant gene regulatory networks that are correlated with cancer, tumor grade and stage in the prostate cancer. To deal with missing values in microarray data, we used a K-nearest-neighbors (KNN) algorithm to determine the precise expression values. We applied web services technology to wrap the bioinformatics toolkits and databases to automatically extract the promoter regions of DNA sequences and predicted the transcription factors that regulate the gene expressions. We adopt the microarray datasets consists of 62 primary tumors, 41 normal prostate tissues from Stanford Microarray Database (SMD) as a target dataset to evaluate our method. The predicted results showed that the possible biomarker genes related to cancer and denoted the androgen functions and processes may be in the development of the prostate cancer and promote the cell death in cell cycle. Our predicted results showed that sub-networks of genes SREBF1, STAT6 and PBX1 are strongly related to a high extent while ETS transcription factors ELK1, JUN and EGR2 are related to a low extent. Gene SLC22A3 may explain clinically the differentiation associated with the high grade cancer compared with low grade cancer. Enhancer of Zeste Homolg 2 (EZH2) regulated by RUNX1 and STAT3 is correlated to the pathological stage. We provide a computational framework to reconstruct

Predicting non-melanoma skin cancer via a multi-parameterized artificial neural network.

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Roffman, David; Hart, Gregory; Girardi, Michael; Ko, Christine J; Deng, Jun

2018-01-26

Ultraviolet radiation (UVR) exposure and family history are major associated risk factors for the development of non-melanoma skin cancer (NMSC). The objective of this study was to develop and validate a multi-parameterized artificial neural network based on available personal health information for early detection of NMSC with high sensitivity and specificity, even in the absence of known UVR exposure and family history. The 1997-2015 NHIS adult survey data used to train and validate our neural network (NN) comprised of 2,056 NMSC and 460,574 non-cancer cases. We extracted 13 parameters for our NN: gender, age, BMI, diabetic status, smoking status, emphysema, asthma, race, Hispanic ethnicity, hypertension, heart diseases, vigorous exercise habits, and history of stroke. This study yielded an area under the ROC curve of 0.81 and 0.81 for training and validation, respectively. Our results (training sensitivity 88.5% and specificity 62.2%, validation sensitivity 86.2% and specificity 62.7%) were comparable to a previous study of basal and squamous cell carcinoma prediction that also included UVR exposure and family history information. These results indicate that our NN is robust enough to make predictions, suggesting that we have identified novel associations and potential predictive parameters of NMSC.

Social networks and social support for healthy eating among Latina breast cancer survivors: implications for social and behavioral interventions.

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Crookes, Danielle M; Shelton, Rachel C; Tehranifar, Parisa; Aycinena, Corina; Gaffney, Ann Ogden; Koch, Pam; Contento, Isobel R; Greenlee, Heather

2016-04-01

Little is known about Latina breast cancer survivors' social networks or their perceived social support to achieve and maintain a healthy diet. This paper describes the social networks and perceived support for healthy eating in a sample of breast cancer survivors of predominantly Dominican descent living in New York City. Spanish-speaking Latina breast cancer survivors enrolled in a randomized controlled trial of a culturally tailored dietary intervention. Social networks were assessed using Cohen's Social Network Index and a modified General Social Survey Social Networks Module that included assessments of shared health promoting behaviors. Perceived social support from family and friends for healthy, food-related behaviors was assessed. Participants' networks consisted predominantly of family and friends. Family members were more likely than other individuals to be identified as close network members. Participants were more likely to share food-related activities than exercise activities with close network members. Perceived social support for healthy eating was high, although perceived support from spouses and children was higher than support from friends. Despite high levels of perceived support, family was also identified as a barrier to eating healthy foods by nearly half of women. Although friends are part of Latina breast cancer survivors' social networks, spouses and children may provide greater support for healthy eating than friends. Involving family members in dietary interventions for Latina breast cancer survivors may tap into positive sources of support for women, which could facilitate uptake and maintenance of healthy eating behaviors.

Assessing needs and assets for building a regional network infrastructure to reduce cancer related health disparities.

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Wells, Kristen J; Lima, Diana S; Meade, Cathy D; Muñoz-Antonia, Teresita; Scarinci, Isabel; McGuire, Allison; Gwede, Clement K; Pledger, W Jack; Partridge, Edward; Lipscomb, Joseph; Matthews, Roland; Matta, Jaime; Flores, Idhaliz; Weiner, Roy; Turner, Timothy; Miele, Lucio; Wiese, Thomas E; Fouad, Mona; Moreno, Carlos S; Lacey, Michelle; Christie, Debra W; Price-Haywood, Eboni G; Quinn, Gwendolyn P; Coppola, Domenico; Sodeke, Stephen O; Green, B Lee; Lichtveld, Maureen Y

2014-06-01

Significant cancer health disparities exist in the United States and Puerto Rico. While numerous initiatives have been implemented to reduce cancer disparities, regional coordination of these efforts between institutions is often limited. To address cancer health disparities nation-wide, a series of regional transdisciplinary networks through the Geographic Management Program (GMaP) and the Minority Biospecimen/Biobanking Geographic Management Program (BMaP) were established in six regions across the country. This paper describes the development of the Region 3 GMaP/BMaP network composed of over 100 investigators from nine institutions in five Southeastern states and Puerto Rico to develop a state-of-the-art network for cancer health disparities research and training. We describe a series of partnership activities that led to the formation of the infrastructure for this network, recount the participatory processes utilized to develop and implement a needs and assets assessment and implementation plan, and describe our approach to data collection. Completion, by all nine institutions, of the needs and assets assessment resulted in several beneficial outcomes for Region 3 GMaP/BMaP. This network entails ongoing commitment from the institutions and institutional leaders, continuous participatory and engagement activities, and effective coordination and communication centered on team science goals. Copyright © 2014 Elsevier Ltd. All rights reserved.

Assessing Needs and Assets for Building a Regional Network Infrastructure to Reduce Cancer Related Health Disparities

Science.gov (United States)

Wells, Kristen J.; Lima, Diana S.; Meade, Cathy D.; Muñoz-Antonia, Teresita; Scarinci, Isabel; McGuire, Allison; Gwede, Clement K.; Pledger, W. Jack; Partridge, Edward; Lipscomb, Joseph; Matthews, Roland; Matta, Jaime; Flores, Idhaliz; Weiner, Roy; Turner, Timothy; Miele, Lucio; Wiese, Thomas E.; Fouad, Mona; Moreno, Carlos S.; Lacey, Michelle; Christie, Debra W.; Price-Haywood, Eboni G.; Quinn, Gwendolyn P.; Coppola, Domenico; Sodeke, Stephen O.; Green, B. Lee; Lichtveld, Maureen Y.

2015-01-01

Significant cancer health disparities exist in the United States and Puerto Rico. While numerous initiatives have been implemented to reduce cancer disparities, regional coordination of these efforts between institutions is often limited. To address cancer health disparities nationwide, a series of regional transdisciplinary networks through the Geographic Management Program (GMaP) and the Minority Biospecimen/Biobanking Geographic Management Program (BMaP) were established in six regions across the country. This paper describes the development of the Region 3 GMaP/BMaP network composed of over 100 investigators from nine institutions in five Southeastern states and Puerto Rico to develop a state-of-the-art network for cancer health disparities research and training. We describe a series of partnership activities that led to the formation of the infrastructure for this network, recount the participatory processes utilized to develop and implement a needs and assets assessment and implementation plan, and describe our approach to data collection. Completion, by all nine institutions, of the needs and assets assessment resulted in several beneficial outcomes for Region 3 GMaP/BMaP. This network entails ongoing commitment from the institutions and institutional leaders, continuous participatory and engagement activities, and effective coordination and communication centered on team science goals. PMID:24486917

The redox biology network in cancer pathophysiology and therapeutics

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Gina Manda

2015-08-01

Full Text Available The review pinpoints operational concepts related to the redox biology network applied to the pathophysiology and therapeutics of solid tumors. A sophisticated network of intrinsic and extrinsic cues, integrated in the tumor niche, drives tumorigenesis and tumor progression. Critical mutations and distorted redox signaling pathways orchestrate pathologic events inside cancer cells, resulting in resistance to stress and death signals, aberrant proliferation and efficient repair mechanisms. Additionally, the complex inter-cellular crosstalk within the tumor niche, mediated by cytokines, redox-sensitive danger signals (HMGB1 and exosomes, under the pressure of multiple stresses (oxidative, inflammatory, metabolic, greatly contributes to the malignant phenotype. The tumor-associated inflammatory stress and its suppressive action on the anti-tumor immune response are highlighted. We further emphasize that ROS may act either as supporter or enemy of cancer cells, depending on the context. Oxidative stress-based therapies, such as radiotherapy and photodynamic therapy, take advantage of the cytotoxic face of ROS for killing tumor cells by a non-physiologically sudden, localized and intense oxidative burst. The type of tumor cell death elicited by these therapies is discussed. Therapy outcome depends on the differential sensitivity to oxidative stress of particular tumor cells, such as cancer stem cells, and therefore co-therapies that transiently down-regulate their intrinsic antioxidant system hold great promise. We draw attention on the consequences of the damage signals delivered by oxidative stress-injured cells to neighboring and distant cells, and emphasize the benefits of therapeutically triggered immunologic cell death in metastatic cancer. An integrative approach should be applied when designing therapeutic strategies in cancer, taking into consideration the mutational, metabolic, inflammatory and oxidative status of tumor cells, cellular

The Asian American Network for Cancer Awareness, Research, and Training’s Role in Cancer Awareness, Research, and Training

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Chen, Moon S.

2006-01-01

Purpose The purpose of this paper is to describe the content for the Asian American Network for Cancer Awareness Research and Training (AANCART) with respect to Asian American demographic characteristics and their cancer burden, highlights of accomplishments in various AANCART regions, aspirations for AANCART, and an interim assessment of AANCART’s activities to date. Methods The author compiled literature and other data references to describe the context for Asian American demographic characteristics and their cancer burden. As the AANCART Principal Investigator, he collected data from internal AANCART reports to depict highlights of accomplishments in various AANCART regions and offer evidence that AANCART’s first two specific aims have been attained. Principal Findings With respect to our first specific aim, we have built an infrastructure for cancer awareness, research and training operationally at a Network-wide basis through program directors for biostatistics, community, clinical, and research and in our four original AANCART regions: New York, Seattle, San Francisco, and Los Angeles. With respect to our second specific aim, we have established partnerships as exemplified by working collaboratively with New York’s Charles B. Wang Community Health Center in securing external funding with them for a tobacco control initiative and nationally with the American Cancer Society. With respect to our third specific aim, we have been fortunate to assist at least eight junior investigators in receiving NCI-funded pilot studies. The most notable change was the transfer of AANCART’s national headquarters from Columbus, Ohio to Sacramento, California along with potentially an increased diversification of Asian American ethnic groups as well as an expansion to Hawaii and Houston. Conclusion As of the end of year 2 of AANCART, AANCART’s two specific aims have been achieved. We are focusing on our third specific aim. PMID:15352772

The emerging potential for network analysis to inform precision cancer medicine.

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Ozturk, Kivilcim; Dow, Michelle; Carlin, Daniel E; Bejar, Rafael; Carter, Hannah

2018-06-14

Precision cancer medicine promises to tailor clinical decisions to patients using genomic information. Indeed, successes of drugs targeting genetic alterations in tumors, such as imatinib that targets BCR-ABL in chronic myelogenous leukemia, have demonstrated the power of this approach. However biological systems are complex, and patients may differ not only by the specific genetic alterations in their tumor, but by more subtle interactions among such alterations. Systems biology and more specifically, network analysis, provides a framework for advancing precision medicine beyond clinical actionability of individual mutations. Here we discuss applications of network analysis to study tumor biology, early methods for N-of-1 tumor genome analysis and the path for such tools to the clinic. Copyright © 2018. Published by Elsevier Ltd.

Combining Pathway Identification and Breast Cancer Survival Prediction via Screening-Network Methods

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Antonella Iuliano

2018-06-01

Full Text Available Breast cancer is one of the most common invasive tumors causing high mortality among women. It is characterized by high heterogeneity regarding its biological and clinical characteristics. Several high-throughput assays have been used to collect genome-wide information for many patients in large collaborative studies. This knowledge has improved our understanding of its biology and led to new methods of diagnosing and treating the disease. In particular, system biology has become a valid approach to obtain better insights into breast cancer biological mechanisms. A crucial component of current research lies in identifying novel biomarkers that can be predictive for breast cancer patient prognosis on the basis of the molecular signature of the tumor sample. However, the high dimension and low sample size of data greatly increase the difficulty of cancer survival analysis demanding for the development of ad-hoc statistical methods. In this work, we propose novel screening-network methods that predict patient survival outcome by screening key survival-related genes and we assess the capability of the proposed approaches using METABRIC dataset. In particular, we first identify a subset of genes by using variable screening techniques on gene expression data. Then, we perform Cox regression analysis by incorporating network information associated with the selected subset of genes. The novelty of this work consists in the improved prediction of survival responses due to the different types of screenings (i.e., a biomedical-driven, data-driven and a combination of the two before building the network-penalized model. Indeed, the combination of the two screening approaches allows us to use the available biological knowledge on breast cancer and complement it with additional information emerging from the data used for the analysis. Moreover, we also illustrate how to extend the proposed approaches to integrate an additional omic layer, such as copy number

Large-Scale Analysis of Network Bistability for Human Cancers

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Shiraishi, Tetsuya; Matsuyama, Shinako; Kitano, Hiroaki

2010-01-01

Protein–protein interaction and gene regulatory networks are likely to be locked in a state corresponding to a disease by the behavior of one or more bistable circuits exhibiting switch-like behavior. Sets of genes could be over-expressed or repressed when anomalies due to disease appear, and the circuits responsible for this over- or under-expression might persist for as long as the disease state continues. This paper shows how a large-scale analysis of network bistability for various human cancers can identify genes that can potentially serve as drug targets or diagnosis biomarkers. PMID:20628618

Network-based identification of biomarkers coexpressed with multiple pathways.

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Guo, Nancy Lan; Wan, Ying-Wooi

2014-01-01

Unraveling complex molecular interactions and networks and incorporating clinical information in modeling will present a paradigm shift in molecular medicine. Embedding biological relevance via modeling molecular networks and pathways has become increasingly important for biomarker identification in cancer susceptibility and metastasis studies. Here, we give a comprehensive overview of computational methods used for biomarker identification, and provide a performance comparison of several network models used in studies of cancer susceptibility, disease progression, and prognostication. Specifically, we evaluated implication networks, Boolean networks, Bayesian networks, and Pearson's correlation networks in constructing gene coexpression networks for identifying lung cancer diagnostic and prognostic biomarkers. The results show that implication networks, implemented in Genet package, identified sets of biomarkers that generated an accurate prediction of lung cancer risk and metastases; meanwhile, implication networks revealed more biologically relevant molecular interactions than Boolean networks, Bayesian networks, and Pearson's correlation networks when evaluated with MSigDB database.

Modeling Cancer Metastasis using Global, Quantitative and Integrative Network Biology

DEFF Research Database (Denmark)

Schoof, Erwin; Erler, Janine

understanding of molecular processes which are fundamental to tumorigenesis. In Article 1, we propose a novel framework for how cancer mutations can be studied by taking into account their effect at the protein network level. In Article 2, we demonstrate how global, quantitative data on phosphorylation dynamics...... can be generated using MS, and how this can be modeled using a computational framework for deciphering kinase-substrate dynamics. This framework is described in depth in Article 3, and covers the design of KinomeXplorer, which allows the prediction of kinases responsible for modulating observed...... phosphorylation dynamics in a given biological sample. In Chapter III, we move into Integrative Network Biology, where, by combining two fundamental technologies (MS & NGS), we can obtain more in-depth insights into the links between cellular phenotype and genotype. Article 4 describes the proof...

Design The Cervical Cancer Detector Use The Artificial Neural Network

International Nuclear Information System (INIS)

Af'idah, Dwi Intan; Widianto, Eko Didik; Setyawan, Budi

2013-01-01

Cancer is one of the contagious diseases that become a public health issue, both in the world and in Indonesia. In the world, 12% of all deaths caused by cancer and is the second killer after cardiovascular disease. Early detection using the IVA is a practical and inexpensive (only requiring acetic acid). However, the accuracy of the method is quite low, as it can not detect the stage of the cancer. While other methods have a better sensitivity than the IVA method, is a method of PAP smear. However, this method is relatively expensive, and requires an experienced pathologist-cytologist. According to the case above, Considered important to make the cancer cervics detector that is used to detect the abnormality and cervical cancer stage and consists of a digital microscope, as well as a computer application based on artificial neural network. The use of cervical cancer detector software and hardware are integrated each other. After the specifications met, the steps to design the cervical cancer detection are: Modifying a conventional microscope by adding a lens, image recording, and the lights, Programming the tools, designing computer applications, Programming features abnormality detection and staging of cancer.

Improving Gastric Cancer Outcome Prediction Using Single Time-Point Artificial Neural Network Models

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Nilsaz-Dezfouli, Hamid; Abu-Bakar, Mohd Rizam; Arasan, Jayanthi; Adam, Mohd Bakri; Pourhoseingholi, Mohamad Amin

2017-01-01

In cancer studies, the prediction of cancer outcome based on a set of prognostic variables has been a long-standing topic of interest. Current statistical methods for survival analysis offer the possibility of modelling cancer survivability but require unrealistic assumptions about the survival time distribution or proportionality of hazard. Therefore, attention must be paid in developing nonlinear models with less restrictive assumptions. Artificial neural network (ANN) models are primarily useful in prediction when nonlinear approaches are required to sift through the plethora of available information. The applications of ANN models for prognostic and diagnostic classification in medicine have attracted a lot of interest. The applications of ANN models in modelling the survival of patients with gastric cancer have been discussed in some studies without completely considering the censored data. This study proposes an ANN model for predicting gastric cancer survivability, considering the censored data. Five separate single time-point ANN models were developed to predict the outcome of patients after 1, 2, 3, 4, and 5 years. The performance of ANN model in predicting the probabilities of death is consistently high for all time points according to the accuracy and the area under the receiver operating characteristic curve. PMID:28469384

German second-opinion network for testicular cancer: sealing the leaky pipe between evidence and clinical practice.

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Zengerling, Friedemann; Hartmann, Michael; Heidenreich, Axel; Krege, Susanne; Albers, Peter; Karl, Alexander; Weissbach, Lothar; Wagner, Walter; Bedke, Jens; Retz, Margitta; Schmelz, Hans U; Kliesch, Sabine; Kuczyk, Markus; Winter, Eva; Pottek, Tobias; Dieckmann, Klaus-Peter; Schrader, Andres Jan; Schrader, Mark

2014-06-01

In 2006, the German Testicular Cancer Study Group initiated an extensive evidence-based national second-opinion network to improve the care of testicular cancer patients. The primary aims were to reflect the current state of testicular cancer treatment in Germany and to analyze the project's effect on the quality of care delivered to testicular cancer patients. A freely available internet-based platform was developed for the exchange of data between the urologists seeking advice and the 31 second-opinion givers. After providing all data relevant to the primary treatment decision, urologists received a second opinion on their therapy plan within testicular cancer patient in Germany were submitted to second-opinion centers. Second-opinion centers can help to improve the implementation of evidence into clinical practice.

A neural network approach to breast cancer diagnosis as a constraint satisfaction problem

International Nuclear Information System (INIS)

Tourassi, Georgia D.; Markey, Mia K.; Lo, Joseph Y.; Floyd, Carey E. Jr.

2001-01-01

A constraint satisfaction neural network (CSNN) approach is proposed for breast cancer diagnosis using mammographic and patient history findings. Initially, the diagnostic decision to biopsy was formulated as a constraint satisfaction problem. Then, an associative memory type neural network was applied to solve the problem. The proposed network has a flexible, nonhierarchical architecture that allows it to operate not only as a predictive tool but also as an analysis tool for knowledge discovery of association rules. The CSNN was developed and evaluated using a database of 500 nonpalpable breast lesions with definitive histopathological diagnosis. The CSNN diagnostic performance was evaluated using receiver operating characteristic analysis (ROC). The results of the study showed that the CSNN ROC area index was 0.84±0.02. The CSNN predictive performance is competitive with that achieved by experienced radiologists and backpropagation artificial neural networks (BP-ANNs) presented before. Furthermore, the study illustrates how CSNN can be used as a knowledge discovery tool overcoming some of the well-known limitations of BP-ANNs

Social networks and mortality based on the Komo-Ise cohort study in Japan.

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Iwasaki, Motoki; Otani, Tetsuya; Sunaga, Rumiko; Miyazaki, Hiroko; Xiao, Liu; Wang, Naren; Yosiaki, Sasazawa; Suzuki, Shosuke

2002-12-01

No prospective studies have examined the association between social networks and all-cause and cause-specific mortality among middle-aged Japanese. The study of varied populations may contribute to clarifying the robustness of the observed effects of social networks and extend their generalizability. To clarify the association between social networks and mortality among middle-aged and elderly Japanese, a community-based prospective study, the Komo-Ise Study, was conducted in two areas of Gunma Prefecture, Japan. A total of 11 565 subjects aged 40-69 years at baseline in 1993 completed a self-administered questionnaire. During the 7-year follow-up period, 335 men and 155 women died and the relative risk (RR) of each social network item was estimated by the Cox proportional hazard model. Single women had significantly increased risks of all-cause (multivariate RR = 2.2), and all circulatory system disease (age-area adjusted RR = 2.6) mortality. Men who did not participate in hobbies, club activities, or community groups had significantly higher multivariate RR for all-cause (RR = 1.5), all circulatory system disease (RR = 1.6) and non-cancer and non-circulatory system disease (RR = 2.3) mortality. Urban women who rarely or never met close relatives had significantly elevated risks of all-cause (RR = 2.4), all cancer (RR = 2.6), and non-cancer and non-circulatory system disease (RR = 2.7) mortality after adjustment for established risk factors. This study provides evidence that social networks are an important predictor of mortality risk for middle-aged and elderly Japanese men and women. Lack of participation, for men, and being single and lack of meeting close relatives, for women, were independent risk factors for mortality.

Network analysis of an in vitro model of androgen-resistance in prostate cancer

International Nuclear Information System (INIS)

Detchokul, Sujitra; Elangovan, Aparna; Crampin, Edmund J.; Davis, Melissa J.; Frauman, Albert G.

2015-01-01

The development of androgen resistance is a major limitation to androgen deprivation treatment in prostate cancer. We have developed an in vitro model of androgen-resistance to characterise molecular changes occurring as androgen resistance evolves over time. Our aim is to understand biological network profiles of transcriptomic changes occurring during the transition to androgen-resistance and to validate these changes between our in vitro model and clinical datasets (paired samples before and after androgen-deprivation therapy of patients with advanced prostate cancer). We established an androgen-independent subline from LNCaP cells by prolonged exposure to androgen-deprivation. We examined phenotypic profiles and performed RNA-sequencing. The reads generated were compared to human clinical samples and were analysed using differential expression, pathway analysis and protein-protein interaction networks. After 24 weeks of androgen-deprivation, LNCaP cells had increased proliferative and invasive behaviour compared to parental LNCaP, and its growth was no longer responsive to androgen. We identified key genes and pathways that overlap between our cell line and clinical RNA sequencing datasets and analysed the overlapping protein-protein interaction network that shared the same pattern of behaviour in both datasets. Mechanisms bypassing androgen receptor signalling pathways are significantly enriched. Several steroid hormone receptors are differentially expressed in both datasets. In particular, the progesterone receptor is significantly differentially expressed and is part of the interaction network disrupted in both datasets. Other signalling pathways commonly altered in prostate cancer, MAPK and PI3K-Akt pathways, are significantly enriched in both datasets. The overlap between the human and cell-line differential expression profiles and protein networks was statistically significant showing that the cell-line model reproduces molecular patterns observed in

Assessing the effect of quantitative and qualitative predictors on gastric cancer individuals survival using hierarchical artificial neural network models.

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Amiri, Zohreh; Mohammad, Kazem; Mahmoudi, Mahmood; Parsaeian, Mahbubeh; Zeraati, Hojjat

2013-01-01

There are numerous unanswered questions in the application of artificial neural network models for analysis of survival data. In most studies, independent variables have been studied as qualitative dichotomous variables, and results of using discrete and continuous quantitative, ordinal, or multinomial categorical predictive variables in these models are not well understood in comparison to conventional models. This study was designed and conducted to examine the application of these models in order to determine the survival of gastric cancer patients, in comparison to the Cox proportional hazards model. We studied the postoperative survival of 330 gastric cancer patients who suffered surgery at a surgical unit of the Iran Cancer Institute over a five-year period. Covariates of age, gender, history of substance abuse, cancer site, type of pathology, presence of metastasis, stage, and number of complementary treatments were entered in the models, and survival probabilities were calculated at 6, 12, 18, 24, 36, 48, and 60 months using the Cox proportional hazards and neural network models. We estimated coefficients of the Cox model and the weights in the neural network (with 3, 5, and 7 nodes in the hidden layer) in the training group, and used them to derive predictions in the study group. Predictions with these two methods were compared with those of the Kaplan-Meier product limit estimator as the gold standard. Comparisons were performed with the Friedman and Kruskal-Wallis tests. Survival probabilities at different times were determined using the Cox proportional hazards and a neural network with three nodes in the hidden layer; the ratios of standard errors with these two methods to the Kaplan-Meier method were 1.1593 and 1.0071, respectively, revealed a significant difference between Cox and Kaplan-Meier (P neural network, and the neural network and the standard (Kaplan-Meier), as well as better accuracy for the neural network (with 3 nodes in the hidden layer

A statistical framework for evaluating neural networks to predict recurrent events in breast cancer

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Gorunescu, Florin; Gorunescu, Marina; El-Darzi, Elia; Gorunescu, Smaranda

2010-07-01

Breast cancer is the second leading cause of cancer deaths in women today. Sometimes, breast cancer can return after primary treatment. A medical diagnosis of recurrent cancer is often a more challenging task than the initial one. In this paper, we investigate the potential contribution of neural networks (NNs) to support health professionals in diagnosing such events. The NN algorithms are tested and applied to two different datasets. An extensive statistical analysis has been performed to verify our experiments. The results show that a simple network structure for both the multi-layer perceptron and radial basis function can produce equally good results, not all attributes are needed to train these algorithms and, finally, the classification performances of all algorithms are statistically robust. Moreover, we have shown that the best performing algorithm will strongly depend on the features of the datasets, and hence, there is not necessarily a single best classifier.

How Can We Treat Cancer Disease Not Cancer Cells?

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Kim, Kyu-Won; Lee, Su-Jae; Kim, Woo-Young; Seo, Ji Hae; Lee, Ho-Young

2017-01-01

Since molecular biology studies began, researches in biological science have centered on proteins and genes at molecular level of a single cell. Cancer research has also focused on various functions of proteins and genes that distinguish cancer cells from normal cells. Accordingly, most contemporary anticancer drugs have been developed to target abnormal characteristics of cancer cells. Despite the great advances in the development of anticancer drugs, vast majority of patients with advanced cancer have shown grim prognosis and high rate of relapse. To resolve this problem, we must reevaluate our focuses in current cancer research. Cancer should be considered as a systemic disease because cancer cells undergo a complex interaction with various surrounding cells in cancer tissue and spread to whole body through metastasis under the control of the systemic modulation. Human body relies on the cooperative interaction between various tissues and organs, and each organ performs its specialized function through tissue-specific cell networks. Therefore, investigation of the tumor-specific cell networks can provide novel strategy to overcome the limitation of current cancer research. This review presents the limitations of the current cancer research, emphasizing the necessity of studying tissue-specific cell network which could be a new perspective on treating cancer disease, not cancer cells.

TGF-β1 targets a microRNA network that regulates cellular adhesion and migration in renal cancer.

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Bogusławska, Joanna; Rodzik, Katarzyna; Popławski, Piotr; Kędzierska, Hanna; Rybicka, Beata; Sokół, Elżbieta; Tański, Zbigniew; Piekiełko-Witkowska, Agnieszka

2018-01-01

In our previous study we found altered expression of 19 adhesion-related genes in renal tumors. In this study we hypothesized that disturbed expression of adhesion-related genes could be caused by microRNAs: short, non-coding RNAs that regulate gene expression. Here, we found that expression of 24 microRNAs predicted to target adhesion-related genes was disturbed in renal tumors and correlated with expression of their predicted targets. miR-25-3p, miR-30a-5p, miR-328 and miR-363-3p directly targeted adhesion-related genes, including COL5A1, COL11A1, ITGA5, MMP16 and THBS2. miR-363-3p and miR-328 inhibited proliferation of renal cancer cells, while miR-25-3p inhibited adhesion, promoted proliferation and migration of renal cancer cells. TGF-β1 influenced the expression of miR-25-3p, miR-30a-5p, and miR-328. The analyzed microRNAs, their target genes and TGF-β1 formed a network of strong correlations in tissue samples from renal cancer patients. The expression signature of microRNAs linked with TGF-β1 levels correlated with poor survival of renal cancer patients. The results of our study suggest that TGF-β1 coordinates the expression of microRNA network that regulates cellular adhesion in cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Changes in Brain Structural Networks and Cognitive Functions in Testicular Cancer Patients Receiving Cisplatin-Based Chemotherapy

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Amidi, Ali; Hosseini, S. M.Hadi; Leemans, Alexander; Kesler, Shelli R.; Agerbæk, Mads; Wu, Lisa M.; Zachariae, Robert

2017-01-01

Background: Cisplatin-based chemotherapy may have neurotoxic effects within the central nervous system. The aims of this study were 1) to longitudinally investigate the impact of cisplatin-based chemotherapy on whole-brain networks in testicular cancer patients undergoing treatment and 2) to explore

Understanding the social and community support networks of American Indian women cancer survivors.

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Burnette, Catherine E; Liddell, Jessica; Roh, Soonhee; Lee, Yeon-Shim; Lee, Hee Yun

2018-04-02

Cancer is the leading cause of death among American Indian and Alaska Native (AI/AN) women, and although cancer disparities among AI women are alarming, there is little research focused on the topic of social support and cancer treatment and outcomes. A community advisory board was used to develop and administer the project, and a qualitative descriptive study methodology was used. This research was conducted in partnership with two community-based hospitals in the Northern Plains. The sample included 43 AI female cancer survivors who were interviewed with a semi-structured interview guide. The data were analyzed using content analysis. Emergent themes revealed that AI cancer survivors' non-familial support systems included friends (n = 12), support groups (n = 6), churches (n = 10), co-workers (n = 5), communities (n = 4), support from health practitioners (n = 3) and additional forms of support. Results indicate that survivors' networks are diverse, and support broad prevention programs that reach out to churches, community groups, and online forums. These sources of supports can be enhanced through sustainable community-based infrastructures.

Biomarkers of Treatment Toxicity in Combined-Modality Cancer Therapies with Radiation and Systemic Drugs: Study Design, Multiplex Methods, Molecular Networks

Directory of Open Access Journals (Sweden)

Anne Hansen Ree

2014-12-01

Full Text Available Organ toxicity in cancer therapy is likely caused by an underlying disposition for given pathophysiological mechanisms in the individual patient. Mechanistic data on treatment toxicity at the patient level are scarce; hence, probabilistic and translational linkages among different layers of data information, all the way from cellular targets of the therapeutic exposure to tissues and ultimately the patient’s organ systems, are required. Throughout all of these layers, untoward treatment effects may be viewed as perturbations that propagate within a hierarchically structured network from one functional level to the next, at each level causing disturbances that reach a critical threshold, which ultimately are manifested as clinical adverse reactions. Advances in bioinformatics permit compilation of information across the various levels of data organization, presumably enabling integrated systems biology-based prediction of treatment safety. In view of the complexity of biological responses to cancer therapy, this communication reports on a “top-down” strategy, starting with the systematic assessment of adverse effects within a defined therapeutic context and proceeding to transcriptomic and proteomic analysis of relevant patient tissue samples and computational exploration of the resulting data, with the ultimate aim of utilizing information from functional connectivity networks in evaluation of patient safety in multimodal cancer therapy.

Classification of breast cancer histology images using Convolutional Neural Networks.

Directory of Open Access Journals (Sweden)

Teresa Araújo

Full Text Available Breast cancer is one of the main causes of cancer death worldwide. The diagnosis of biopsy tissue with hematoxylin and eosin stained images is non-trivial and specialists often disagree on the final diagnosis. Computer-aided Diagnosis systems contribute to reduce the cost and increase the efficiency of this process. Conventional classification approaches rely on feature extraction methods designed for a specific problem based on field-knowledge. To overcome the many difficulties of the feature-based approaches, deep learning methods are becoming important alternatives. A method for the classification of hematoxylin and eosin stained breast biopsy images using Convolutional Neural Networks (CNNs is proposed. Images are classified in four classes, normal tissue, benign lesion, in situ carcinoma and invasive carcinoma, and in two classes, carcinoma and non-carcinoma. The architecture of the network is designed to retrieve information at different scales, including both nuclei and overall tissue organization. This design allows the extension of the proposed system to whole-slide histology images. The features extracted by the CNN are also used for training a Support Vector Machine classifier. Accuracies of 77.8% for four class and 83.3% for carcinoma/non-carcinoma are achieved. The sensitivity of our method for cancer cases is 95.6%.

Constructing disease-specific gene networks using pair-wise relevance metric: Application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements

Directory of Open Access Journals (Sweden)

Jiang Wei

2008-08-01

Full Text Available Abstract Background With the advance of large-scale omics technologies, it is now feasible to reversely engineer the underlying genetic networks that describe the complex interplays of molecular elements that lead to complex diseases. Current networking approaches are mainly focusing on building genetic networks at large without probing the interaction mechanisms specific to a physiological or disease condition. The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases. Results The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8 (p ≈ 0, desmin (DES (p = 2.71 × 10-6 and enolase 1 (ENO1 (p = 4.19 × 10-5], while two novel hub genes [RNA binding motif protein 9 (RBM9 (p = 1.50 × 10-4 and ribosomal protein L30 (RPL30 (p = 1.50 × 10-4] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO based analysis of the colon cancer-specific gene network and

Constructing disease-specific gene networks using pair-wise relevance metric: application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements.

Science.gov (United States)

Jiang, Wei; Li, Xia; Rao, Shaoqi; Wang, Lihong; Du, Lei; Li, Chuanxing; Wu, Chao; Wang, Hongzhi; Wang, Yadong; Yang, Baofeng

2008-08-10

With the advance of large-scale omics technologies, it is now feasible to reversely engineer the underlying genetic networks that describe the complex interplays of molecular elements that lead to complex diseases. Current networking approaches are mainly focusing on building genetic networks at large without probing the interaction mechanisms specific to a physiological or disease condition. The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases. The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8) (p approximately 0), desmin (DES) (p = 2.71 x 10(-6)) and enolase 1 (ENO1) (p = 4.19 x 10(-5))], while two novel hub genes [RNA binding motif protein 9 (RBM9) (p = 1.50 x 10(-4)) and ribosomal protein L30 (RPL30) (p = 1.50 x 10(-4))] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO) based analysis of the colon cancer-specific gene network and the sub-network that

Satisfaction with support versus size of network: differential effects of social support on psychological distress in parents of pediatric cancer patients.

Science.gov (United States)

Harper, Felicity W K; Peterson, Amy M; Albrecht, Terrance L; Taub, Jeffrey W; Phipps, Sean; Penner, Louis A

2016-05-01

This study examined the direct and buffering effects of social support on longer-term global psychological distress among parents coping with pediatric cancer. In both sets of analyses, we examined whether these effects depended on the dimension of social support provided (i.e., satisfaction with support versus size of support network). Participants were 102 parents of pediatric cancer patients. At study entry, parents reported their trait anxiety, depression, and two dimensions of their social support network (satisfaction with support and size of support network). Parents subsequently reported their psychological distress in 3- and 9-month follow-up assessments. Parents' satisfaction with support had a direct effect on longer-term psychological distress; satisfaction was negatively associated with distress at both follow-ups. In contrast, size of support network buffered (moderated) the impact of trait anxiety and depression on later distress. Parents with smaller support networks and higher levels of trait anxiety and depression at baseline had higher levels of psychological distress at both follow-ups; for parents with larger support networks, there was no relationship. Social support can attenuate psychological distress in parents coping with pediatric cancer; however, the nature of the effect depends on the dimension of support. Whereas interventions that focus on increasing satisfaction with social support may benefit all parents, at-risk parents will likely benefit from interventions that ensure they have an adequate number of support resources. Copyright © 2015 John Wiley & Sons, Ltd.

FERAL : Network-based classifier with application to breast cancer outcome prediction

NARCIS (Netherlands)

Allahyar, A.; De Ridder, J.

2015-01-01

Motivation: Breast cancer outcome prediction based on gene expression profiles is an important strategy for personalize patient care. To improve performance and consistency of discovered markers of the initial molecular classifiers, network-based outcome prediction methods (NOPs) have been proposed.

Hypoxia induces a phase transition within a kinase signaling network in cancer cells

Science.gov (United States)

Wei, Wei; Shi, Qihui; Remacle, Francoise; Qin, Lidong; Shackelford, David B.; Shin, Young Shik; Mischel, Paul S.; Levine, R. D.; Heath, James R.

2013-01-01

Hypoxia is a near-universal feature of cancer, promoting glycolysis, cellular proliferation, and angiogenesis. The molecular mechanisms of hypoxic signaling have been intensively studied, but the impact of changes in oxygen partial pressure (pO2) on the state of signaling networks is less clear. In a glioblastoma multiforme (GBM) cancer cell model, we examined the response of signaling networks to targeted pathway inhibition between 21% and 1% pO2. We used a microchip technology that facilitates quantification of a panel of functional proteins from statistical numbers of single cells. We find that near 1.5% pO2, the signaling network associated with mammalian target of rapamycin (mTOR) complex 1 (mTORC1)—a critical component of hypoxic signaling and a compelling cancer drug target—is deregulated in a manner such that it will be unresponsive to mTOR kinase inhibitors near 1.5% pO2, but will respond at higher or lower pO2 values. These predictions were validated through experiments on bulk GBM cell line cultures and on neurosphere cultures of a human-origin GBM xenograft tumor. We attempt to understand this behavior through the use of a quantitative version of Le Chatelier’s principle, as well as through a steady-state kinetic model of protein interactions, both of which indicate that hypoxia can influence mTORC1 signaling as a switch. The Le Chatelier approach also indicates that this switch may be thought of as a type of phase transition. Our analysis indicates that certain biologically complex cell behaviors may be understood using fundamental, thermodynamics-motivated principles. PMID:23530221

Hypoxia induces a phase transition within a kinase signaling network in cancer cells.

Science.gov (United States)

Wei, Wei; Shi, Qihui; Remacle, Francoise; Qin, Lidong; Shackelford, David B; Shin, Young Shik; Mischel, Paul S; Levine, R D; Heath, James R

2013-04-09

Hypoxia is a near-universal feature of cancer, promoting glycolysis, cellular proliferation, and angiogenesis. The molecular mechanisms of hypoxic signaling have been intensively studied, but the impact of changes in oxygen partial pressure (pO2) on the state of signaling networks is less clear. In a glioblastoma multiforme (GBM) cancer cell model, we examined the response of signaling networks to targeted pathway inhibition between 21% and 1% pO2. We used a microchip technology that facilitates quantification of a panel of functional proteins from statistical numbers of single cells. We find that near 1.5% pO2, the signaling network associated with mammalian target of rapamycin (mTOR) complex 1 (mTORC1)--a critical component of hypoxic signaling and a compelling cancer drug target--is deregulated in a manner such that it will be unresponsive to mTOR kinase inhibitors near 1.5% pO2, but will respond at higher or lower pO2 values. These predictions were validated through experiments on bulk GBM cell line cultures and on neurosphere cultures of a human-origin GBM xenograft tumor. We attempt to understand this behavior through the use of a quantitative version of Le Chatelier's principle, as well as through a steady-state kinetic model of protein interactions, both of which indicate that hypoxia can influence mTORC1 signaling as a switch. The Le Chatelier approach also indicates that this switch may be thought of as a type of phase transition. Our analysis indicates that certain biologically complex cell behaviors may be understood using fundamental, thermodynamics-motivated principles.

A Prescription for Internet Access: Appealing to Middle-Aged and Older Racial and Ethnic Minorities Through Social Network Sites to Combat Colorectal Cancer.

Science.gov (United States)

Lumpkins, Crystal Y; Mabachi, Natabhona; Lee, Jaehoon; Pacheco, Christina; Greiner, K Allen; Geana, Mugur

2017-07-01

The popularity and usage of social media networks or SNS (social networking sites) among American Internet users age 50 and over doubled between 2009 and 2010 and has steadily climbed. Part of this increased access may be the result of older adults who are living with a chronic disease and are reaching out for online support. Colorectal cancer (CRC) risk is among those concerns, particularly among middle-age and older minority populations where disparities exist. This exploratory study investigates information seeking behavior related to cancer factors (e.g. testing for colon cancer, cancer fatalism) and current social media usage among racial and ethnic minority groups (African American and Latinos) and Whites age 50 and older. The secondary data from the 2012 Health Information National Trends Survey (HINTS) was analyzed to compare these populations. Results show that African Americans and Latinos were only slightly more likely to use social network sites to seek out cancer information compared to Whites. However, Whites were more likely to use the Internet to seek health information compared to African Americans and Latinos. In this sample, Whites were also more likely to be informed by a physician about CRC testing (p social media networks, Internet sites) have increased among older Americans and can serve as critical channels for cancer information and education.

Comment on 'Deep convolutional neural network with transfer learning for rectum toxicity prediction in cervical cancer radiotherapy: a feasibility study'.

Science.gov (United States)

Valdes, Gilmer; Interian, Yannet

2018-03-15

The application of machine learning (ML) presents tremendous opportunities for the field of oncology, thus we read 'Deep convolutional neural network with transfer learning for rectum toxicity prediction in cervical cancer radiotherapy: a feasibility study' with great interest. In this article, the authors used state of the art techniques: a pre-trained convolutional neural network (VGG-16 CNN), transfer learning, data augmentation, drop out and early stopping, all of which are directly responsible for the success and the excitement that these algorithms have created in other fields. We believe that the use of these techniques can offer tremendous opportunities in the field of Medical Physics and as such we would like to praise the authors for their pioneering application to the field of Radiation Oncology. That being said, given that the field of Medical Physics has unique characteristics that differentiate us from those fields where these techniques have been applied successfully, we would like to raise some points for future discussion and follow up studies that could help the community understand the limitations and nuances of deep learning techniques.

Model-based global sensitivity analysis as applied to identification of anti-cancer drug targets and biomarkers of drug resistance in the ErbB2/3 network

Science.gov (United States)

Lebedeva, Galina; Sorokin, Anatoly; Faratian, Dana; Mullen, Peter; Goltsov, Alexey; Langdon, Simon P.; Harrison, David J.; Goryanin, Igor

2012-01-01

High levels of variability in cancer-related cellular signalling networks and a lack of parameter identifiability in large-scale network models hamper translation of the results of modelling studies into the process of anti-cancer drug development. Recently global sensitivity analysis (GSA) has been recognised as a useful technique, capable of addressing the uncertainty of the model parameters and generating valid predictions on parametric sensitivities. Here we propose a novel implementation of model-based GSA specially designed to explore how multi-parametric network perturbations affect signal propagation through cancer-related networks. We use area-under-the-curve for time course of changes in phosphorylation of proteins as a characteristic for sensitivity analysis and rank network parameters with regard to their impact on the level of key cancer-related outputs, separating strong inhibitory from stimulatory effects. This allows interpretation of the results in terms which can incorporate the effects of potential anti-cancer drugs on targets and the associated biological markers of cancer. To illustrate the method we applied it to an ErbB signalling network model and explored the sensitivity profile of its key model readout, phosphorylated Akt, in the absence and presence of the ErbB2 inhibitor pertuzumab. The method successfully identified the parameters associated with elevation or suppression of Akt phosphorylation in the ErbB2/3 network. From analysis and comparison of the sensitivity profiles of pAkt in the absence and presence of targeted drugs we derived predictions of drug targets, cancer-related biomarkers and generated hypotheses for combinatorial therapy. Several key predictions have been confirmed in experiments using human ovarian carcinoma cell lines. We also compared GSA-derived predictions with the results of local sensitivity analysis and discuss the applicability of both methods. We propose that the developed GSA procedure can serve as a

Identifying the Gene Signatures from Gene-Pathway Bipartite Network Guarantees the Robust Model Performance on Predicting the Cancer Prognosis

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Li He

2014-01-01

Full Text Available For the purpose of improving the prediction of cancer prognosis in the clinical researches, various algorithms have been developed to construct the predictive models with the gene signatures detected by DNA microarrays. Due to the heterogeneity of the clinical samples, the list of differentially expressed genes (DEGs generated by the statistical methods or the machine learning algorithms often involves a number of false positive genes, which are not associated with the phenotypic differences between the compared clinical conditions, and subsequently impacts the reliability of the predictive models. In this study, we proposed a strategy, which combined the statistical algorithm with the gene-pathway bipartite networks, to generate the reliable lists of cancer-related DEGs and constructed the models by using support vector machine for predicting the prognosis of three types of cancers, namely, breast cancer, acute myeloma leukemia, and glioblastoma. Our results demonstrated that, combined with the gene-pathway bipartite networks, our proposed strategy can efficiently generate the reliable cancer-related DEG lists for constructing the predictive models. In addition, the model performance in the swap analysis was similar to that in the original analysis, indicating the robustness of the models in predicting the cancer outcomes.

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

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Komatsu, Yukihisa

1987-10-01

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

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

International Nuclear Information System (INIS)

Komatsu, Yukihisa

1987-01-01

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

TCGA study identifies genomic features of cervical cancer

Science.gov (United States)

Investigators with The Cancer Genome Atlas (TCGA) Research Network have identified novel genomic and molecular characteristics of cervical cancer that will aid in subclassification of the disease and may help target therapies that are most appropriate for each patient.

Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion

Science.gov (United States)

House, Carrie D.; Vaske, Charles J.; Schwartz, Arnold M.; Obias, Vincent; Frank, Bryan; Luu, Truong; Sarvazyan, Narine; Irby, Rosalyn; Strausberg, Robert L.; Hales, Tim G.; Stuart, Joshua M.; Lee, Norman H.

2010-01-01

Voltage-gated Na+ channels (VGSCs) have been implicated in the metastatic potential of human breast, prostate and lung cancer cells. Specifically, the SCN5A gene encoding the VGSC isotype Nav1.5 has been defined as a key driver of human cancer cell invasion. In this study, we examined the expression and function of VGSCs in a panel of colon cancer cell lines by electrophysiological recordings. Na+ channel activity and invasive potential were inhibited pharmacologically by tetrodotoxin or genetically by siRNAs specifically targeting SCN5A. Clinical relevance was established by immunohistochemistry of patient biopsies, where there was strong Nav1.5 protein staining in colon cancer specimens but little to no staining in matched-paired normal colon tissues. We explored the mechanism of VGSC-mediated invasive potential on the basis of reported links between VGSC activity and gene expression in excitable cells. Probabilistic modeling of loss-of-function screens and microarray data established an unequivocal role of VGSC SCN5A as a high level regulator of a colon cancer invasion network, involving genes that encompass Wnt signaling, cell migration, ectoderm development, response to biotic stimulus, steroid metabolic process and cell cycle control. siRNA-mediated knockdown of predicted downstream network components caused a loss of invasive behavior, demonstrating network connectivity and its function in driving colon cancer invasion. PMID:20651255

Variation in Definitive Therapy for Localized Non-Small Cell Lung Cancer Among National Comprehensive Cancer Network Institutions

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Valle, Luca F. [Geisel School of Medicine at Dartmouth College, Dartmouth College, Hanover, New Hampshire (United States); Jagsi, Reshma [Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan (United States); Bobiak, Sarah N.; Zornosa, Carrie [National Comprehensive Cancer Network, Fort Washington, Pennsylvania (United States); D' Amico, Thomas A. [Department of Surgery, Division of Thoracic Surgery, Duke Cancer Institute, Durham, North Carolina (United States); Pisters, Katherine M. [Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dexter, Elisabeth U. [Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, New York (United States); Niland, Joyce C. [Department of Information Sciences, City of Hope Comprehensive Cancer Center, Duarte, California (United States); Hayman, James A. [Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan (United States); Kapadia, Nirav S., E-mail: Nirav.S.Kapadia@hitchcock.org [Department of Radiation Oncology, Dartmouth-Hitchcock Norris Cotton Cancer Center, Lebanon, New Hampshire (United States); Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire (United States)

2016-02-01

Purpose: This study determined practice patterns in the staging and treatment of patients with stage I non-small cell lung cancer (NSCLC) among National Comprehensive Cancer Network (NCCN) member institutions. Secondary aims were to determine trends in the use of definitive therapy, predictors of treatment type, and acute adverse events associated with primary modalities of treatment. Methods and Materials: Data from the National Comprehensive Cancer Network Oncology Outcomes Database from 2007 to 2011 for US patients with stage I NSCLC were used. Main outcome measures included patterns of care, predictors of treatment, acute morbidity, and acute mortality. Results: Seventy-nine percent of patients received surgery, 16% received definitive radiation therapy (RT), and 3% were not treated. Seventy-four percent of the RT patients received stereotactic body RT (SBRT), and the remainder received nonstereotactic RT (NSRT). Among participating NCCN member institutions, the number of surgeries-to-RT course ratios varied between 1.6 and 34.7 (P<.01), and the SBRT-to-NSRT ratio varied between 0 and 13 (P=.01). Significant variations were also observed in staging practices, with brain imaging 0.33 (0.25-0.43) times as likely and mediastinoscopy 31.26 (21.84-44.76) times more likely for surgical patients than for RT patients. Toxicity rates for surgical and for SBRT patients were similar, although the rates were double for NSRT patients. Conclusions: The variations in treatment observed among NCCN institutions reflects the lack of level I evidence directing the use of surgery or SBRT for stage I NSCLC. In this setting, research of patient and physician preferences may help to guide future decision making.

Variation in Definitive Therapy for Localized Non-Small Cell Lung Cancer Among National Comprehensive Cancer Network Institutions

International Nuclear Information System (INIS)

Valle, Luca F.; Jagsi, Reshma; Bobiak, Sarah N.; Zornosa, Carrie; D'Amico, Thomas A.; Pisters, Katherine M.; Dexter, Elisabeth U.; Niland, Joyce C.; Hayman, James A.; Kapadia, Nirav S.

2016-01-01

Purpose: This study determined practice patterns in the staging and treatment of patients with stage I non-small cell lung cancer (NSCLC) among National Comprehensive Cancer Network (NCCN) member institutions. Secondary aims were to determine trends in the use of definitive therapy, predictors of treatment type, and acute adverse events associated with primary modalities of treatment. Methods and Materials: Data from the National Comprehensive Cancer Network Oncology Outcomes Database from 2007 to 2011 for US patients with stage I NSCLC were used. Main outcome measures included patterns of care, predictors of treatment, acute morbidity, and acute mortality. Results: Seventy-nine percent of patients received surgery, 16% received definitive radiation therapy (RT), and 3% were not treated. Seventy-four percent of the RT patients received stereotactic body RT (SBRT), and the remainder received nonstereotactic RT (NSRT). Among participating NCCN member institutions, the number of surgeries-to-RT course ratios varied between 1.6 and 34.7 (P<.01), and the SBRT-to-NSRT ratio varied between 0 and 13 (P=.01). Significant variations were also observed in staging practices, with brain imaging 0.33 (0.25-0.43) times as likely and mediastinoscopy 31.26 (21.84-44.76) times more likely for surgical patients than for RT patients. Toxicity rates for surgical and for SBRT patients were similar, although the rates were double for NSRT patients. Conclusions: The variations in treatment observed among NCCN institutions reflects the lack of level I evidence directing the use of surgery or SBRT for stage I NSCLC. In this setting, research of patient and physician preferences may help to guide future decision making.

Predictive genomics: A cancer hallmark network framework for predicting tumor clinical phenotypes using genome sequencing data

OpenAIRE

Wang, Edwin; Zaman, Naif; Mcgee, Shauna; Milanese, Jean-Sébastien; Masoudi-Nejad, Ali; O'Connor, Maureen

2014-01-01

We discuss a cancer hallmark network framework for modelling genome-sequencing data to predict cancer clonal evolution and associated clinical phenotypes. Strategies of using this framework in conjunction with genome sequencing data in an attempt to predict personalized drug targets, drug resistance, and metastasis for a cancer patient, as well as cancer risks for a healthy individual are discussed. Accurate prediction of cancer clonal evolution and clinical phenotypes will have substantial i...

MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

Science.gov (United States)

Wang, Jian; Du, Yong; Liu, Xiaoming; Cho, William C.; Yang, Yinxue

2015-01-01

MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed. PMID:26064956

MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer.

Science.gov (United States)

Wang, Jian; Du, Yong; Liu, Xiaoming; Cho, William C; Yang, Yinxue

2015-01-01

MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.

MicroRNAs as Regulator of Signaling Networks in Metastatic Colon Cancer

Directory of Open Access Journals (Sweden)

Jian Wang

2015-01-01

Full Text Available MicroRNAs (miRNAs are a class of small, noncoding RNA molecules capable of regulating gene expression translationally and/or transcriptionally. A large number of evidence have demonstrated that miRNAs have a functional role in both physiological and pathological processes by regulating the expression of their target genes. Recently, the functionalities of miRNAs in the initiation, progression, angiogenesis, metastasis, and chemoresistance of tumors have gained increasing attentions. Particularly, the alteration of miRNA profiles has been correlated with the transformation and metastasis of various cancers, including colon cancer. This paper reports the latest findings on miRNAs involved in different signaling networks leading to colon cancer metastasis, mainly focusing on miRNA profiling and their roles in PTEN/PI3K, EGFR, TGFβ, and p53 signaling pathways of metastatic colon cancer. The potential of miRNAs used as biomarkers in the diagnosis, prognosis, and therapeutic targets in colon cancer is also discussed.

A Gene Gravity Model for the Evolution of Cancer Genomes: A Study of 3,000 Cancer Genomes across 9 Cancer Types

Science.gov (United States)

Lin, Chen-Ching; Zhao, Junfei; Jia, Peilin; Li, Wen-Hsiung; Zhao, Zhongming

2015-01-01

Cancer development and progression result from somatic evolution by an accumulation of genomic alterations. The effects of those alterations on the fitness of somatic cells lead to evolutionary adaptations such as increased cell proliferation, angiogenesis, and altered anticancer drug responses. However, there are few general mathematical models to quantitatively examine how perturbations of a single gene shape subsequent evolution of the cancer genome. In this study, we proposed the gene gravity model to study the evolution of cancer genomes by incorporating the genome-wide transcription and somatic mutation profiles of ~3,000 tumors across 9 cancer types from The Cancer Genome Atlas into a broad gene network. We found that somatic mutations of a cancer driver gene may drive cancer genome evolution by inducing mutations in other genes. This functional consequence is often generated by the combined effect of genetic and epigenetic (e.g., chromatin regulation) alterations. By quantifying cancer genome evolution using the gene gravity model, we identified six putative cancer genes (AHNAK, COL11A1, DDX3X, FAT4, STAG2, and SYNE1). The tumor genomes harboring the nonsynonymous somatic mutations in these genes had a higher mutation density at the genome level compared to the wild-type groups. Furthermore, we provided statistical evidence that hypermutation of cancer driver genes on inactive X chromosomes is a general feature in female cancer genomes. In summary, this study sheds light on the functional consequences and evolutionary characteristics of somatic mutations during tumorigenesis by propelling adaptive cancer genome evolution, which would provide new perspectives for cancer research and therapeutics. PMID:26352260

Inferring gene dependency network specific to phenotypic alteration based on gene expression data and clinical information of breast cancer.

Science.gov (United States)

Zhou, Xionghui; Liu, Juan

2014-01-01

Although many methods have been proposed to reconstruct gene regulatory network, most of them, when applied in the sample-based data, can not reveal the gene regulatory relations underlying the phenotypic change (e.g. normal versus cancer). In this paper, we adopt phenotype as a variable when constructing the gene regulatory network, while former researches either neglected it or only used it to select the differentially expressed genes as the inputs to construct the gene regulatory network. To be specific, we integrate phenotype information with gene expression data to identify the gene dependency pairs by using the method of conditional mutual information. A gene dependency pair (A,B) means that the influence of gene A on the phenotype depends on gene B. All identified gene dependency pairs constitute a directed network underlying the phenotype, namely gene dependency network. By this way, we have constructed gene dependency network of breast cancer from gene expression data along with two different phenotype states (metastasis and non-metastasis). Moreover, we have found the network scale free, indicating that its hub genes with high out-degrees may play critical roles in the network. After functional investigation, these hub genes are found to be biologically significant and specially related to breast cancer, which suggests that our gene dependency network is meaningful. The validity has also been justified by literature investigation. From the network, we have selected 43 discriminative hubs as signature to build the classification model for distinguishing the distant metastasis risks of breast cancer patients, and the result outperforms those classification models with published signatures. In conclusion, we have proposed a promising way to construct the gene regulatory network by using sample-based data, which has been shown to be effective and accurate in uncovering the hidden mechanism of the biological process and identifying the gene signature for

Cancer-related marketing centrality motifs acting as pivot units in the human signaling network and mediating cross-talk between biological pathways.

Science.gov (United States)

Li, Wan; Chen, Lina; Li, Xia; Jia, Xu; Feng, Chenchen; Zhang, Liangcai; He, Weiming; Lv, Junjie; He, Yuehan; Li, Weiguo; Qu, Xiaoli; Zhou, Yanyan; Shi, Yuchen

2013-12-01

Network motifs in central positions are considered to not only have more in-coming and out-going connections but are also localized in an area where more paths reach the networks. These central motifs have been extensively investigated to determine their consistent functions or associations with specific function categories. However, their functional potentials in the maintenance of cross-talk between different functional communities are unclear. In this paper, we constructed an integrated human signaling network from the Pathway Interaction Database. We identified 39 essential cancer-related motifs in central roles, which we called cancer-related marketing centrality motifs, using combined centrality indices on the system level. Our results demonstrated that these cancer-related marketing centrality motifs were pivotal units in the signaling network, and could mediate cross-talk between 61 biological pathways (25 could be mediated by one motif on average), most of which were cancer-related pathways. Further analysis showed that molecules of most marketing centrality motifs were in the same or adjacent subcellular localizations, such as the motif containing PI3K, PDK1 and AKT1 in the plasma membrane, to mediate signal transduction between 32 cancer-related pathways. Finally, we analyzed the pivotal roles of cancer genes in these marketing centrality motifs in the pathogenesis of cancers, and found that non-cancer genes were potential cancer-related genes.

A social network analysis of treatment discoveries in cancer.

Directory of Open Access Journals (Sweden)

Athanasios Tsalatsanis

2011-03-01

Full Text Available Controlled clinical trials are widely considered to be the vehicle to treatment discovery in cancer that leads to significant improvements in health outcomes including an increase in life expectancy. We have previously shown that the pattern of therapeutic discovery in randomized controlled trials (RCTs can be described by a power law distribution. However, the mechanism generating this pattern is unknown. Here, we propose an explanation in terms of the social relations between researchers in RCTs. We use social network analysis to study the impact of interactions between RCTs on treatment success. Our dataset consists of 280 phase III RCTs conducted by the NCI from 1955 to 2006. The RCT networks are formed through trial interactions formed i at random, ii based on common characteristics, or iii based on treatment success. We analyze treatment success in terms of survival hazard ratio as a function of the network structures. Our results show that the discovery process displays power law if there are preferential interactions between trials that may stem from researchers' tendency to interact selectively with established and successful peers. Furthermore, the RCT networks are "small worlds": trials are connected through a small number of ties, yet there is much clustering among subsets of trials. We also find that treatment success (improved survival is proportional to the network centrality measures of closeness and betweenness. Negative correlation exists between survival and the extent to which trials operate within a limited scope of information. Finally, the trials testing curative treatments in solid tumors showed the highest centrality and the most influential group was the ECOG. We conclude that the chances of discovering life-saving treatments are directly related to the richness of social interactions between researchers inherent in a preferential interaction model.

Signaling Network Assessment of Mutations and Copy Number Variations Predict Breast Cancer Subtype-Specific Drug Targets

Directory of Open Access Journals (Sweden)

Naif Zaman

2013-10-01

Full Text Available Individual cancer cells carry a bewildering number of distinct genomic alterations (e.g., copy number variations and mutations, making it a challenge to uncover genomic-driven mechanisms governing tumorigenesis. Here, we performed exome sequencing on several breast cancer cell lines that represent two subtypes, luminal and basal. We integrated these sequencing data and functional RNAi screening data (for the identification of genes that are essential for cell proliferation and survival onto a human signaling network. Two subtype-specific networks that potentially represent core-signaling mechanisms underlying tumorigenesis were identified. Within both networks, we found that genes were differentially affected in different cell lines; i.e., in some cell lines a gene was identified through RNAi screening, whereas in others it was genomically altered. Interestingly, we found that highly connected network genes could be used to correctly classify breast tumors into subtypes on the basis of genomic alterations. Further, the networks effectively predicted subtype-specific drug targets, which were experimentally validated.

Genome network medicine: innovation to overcome huge challenges in cancer therapy.

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Roukos, Dimitrios H

2014-01-01

The post-ENCODE era shapes now a new biomedical research direction for understanding transcriptional and signaling networks driving gene expression and core cellular processes such as cell fate, survival, and apoptosis. Over the past half century, the Francis Crick 'central dogma' of single n gene/protein-phenotype (trait/disease) has defined biology, human physiology, disease, diagnostics, and drugs discovery. However, the ENCODE project and several other genomic studies using high-throughput sequencing technologies, computational strategies, and imaging techniques to visualize regulatory networks, provide evidence that transcriptional process and gene expression are regulated by highly complex dynamic molecular and signaling networks. This Focus article describes the linear experimentation-based limitations of diagnostics and therapeutics to cure advanced cancer and the need to move on from reductionist to network-based approaches. With evident a wide genomic heterogeneity, the power and challenges of next-generation sequencing (NGS) technologies to identify a patient's personal mutational landscape for tailoring the best target drugs in the individual patient are discussed. However, the available drugs are not capable of targeting aberrant signaling networks and research on functional transcriptional heterogeneity and functional genome organization is poorly understood. Therefore, the future clinical genome network medicine aiming at overcoming multiple problems in the new fields of regulatory DNA mapping, noncoding RNA, enhancer RNAs, and dynamic complexity of transcriptional circuitry are also discussed expecting in new innovation technology and strong appreciation of clinical data and evidence-based medicine. The problematic and potential solutions in the discovery of next-generation, molecular, and signaling circuitry-based biomarkers and drugs are explored. © 2013 Wiley Periodicals, Inc.

Development of the Moffitt Cancer Network as a Telemedicine and Teleconferencing Educational Tool for Health Care Providers

National Research Council Canada - National Science Library

Krischer, Jeffrey

2002-01-01

The Moffitt Cancer Network's (MCN) goal is to provide up-to-date oncology related information, resources, and education to oncology health care providers and researchers for the prevention and cure of cancer...

Wisconsin’s Environmental Public Health Tracking Network: Information Systems Design for Childhood Cancer Surveillance

Science.gov (United States)

Hanrahan, Lawrence P.; Anderson, Henry A.; Busby, Brian; Bekkedal, Marni; Sieger, Thomas; Stephenson, Laura; Knobeloch, Lynda; Werner, Mark; Imm, Pamela; Olson, Joseph

2004-01-01

In this article we describe the development of an information system for environmental childhood cancer surveillance. The Wisconsin Cancer Registry annually receives more than 25,000 incident case reports. Approximately 269 cases per year involve children. Over time, there has been considerable community interest in understanding the role the environment plays as a cause of these cancer cases. Wisconsin’s Public Health Information Network (WI-PHIN) is a robust web portal integrating both Health Alert Network and National Electronic Disease Surveillance System components. WI-PHIN is the information technology platform for all public health surveillance programs. Functions include the secure, automated exchange of cancer case data between public health–based and hospital-based cancer registrars; web-based supplemental data entry for environmental exposure confirmation and hypothesis testing; automated data analysis, visualization, and exposure–outcome record linkage; directories of public health and clinical personnel for role-based access control of sensitive surveillance information; public health information dissemination and alerting; and information technology security and critical infrastructure protection. For hypothesis generation, cancer case data are sent electronically to WI-PHIN and populate the integrated data repository. Environmental data are linked and the exposure–disease relationships are explored using statistical tools for ecologic exposure risk assessment. For hypothesis testing, case–control interviews collect exposure histories, including parental employment and residential histories. This information technology approach can thus serve as the basis for building a comprehensive system to assess environmental cancer etiology. PMID:15471739

Google goes cancer: improving outcome prediction for cancer patients by network-based ranking of marker genes.

Directory of Open Access Journals (Sweden)

Christof Winter

Full Text Available Predicting the clinical outcome of cancer patients based on the expression of marker genes in their tumors has received increasing interest in the past decade. Accurate predictors of outcome and response to therapy could be used to personalize and thereby improve therapy. However, state of the art methods used so far often found marker genes with limited prediction accuracy, limited reproducibility, and unclear biological relevance. To address this problem, we developed a novel computational approach to identify genes prognostic for outcome that couples gene expression measurements from primary tumor samples with a network of known relationships between the genes. Our approach ranks genes according to their prognostic relevance using both expression and network information in a manner similar to Google's PageRank. We applied this method to gene expression profiles which we obtained from 30 patients with pancreatic cancer, and identified seven candidate marker genes prognostic for outcome. Compared to genes found with state of the art methods, such as Pearson correlation of gene expression with survival time, we improve the prediction accuracy by up to 7%. Accuracies were assessed using support vector machine classifiers and Monte Carlo cross-validation. We then validated the prognostic value of our seven candidate markers using immunohistochemistry on an independent set of 412 pancreatic cancer samples. Notably, signatures derived from our candidate markers were independently predictive of outcome and superior to established clinical prognostic factors such as grade, tumor size, and nodal status. As the amount of genomic data of individual tumors grows rapidly, our algorithm meets the need for powerful computational approaches that are key to exploit these data for personalized cancer therapies in clinical practice.

Artificial neural networks for processing fluorescence spectroscopy data in skin cancer diagnostics

International Nuclear Information System (INIS)

Lenhardt, L; Zeković, I; Dramićanin, T; Dramićanin, M D

2013-01-01

Over the years various optical spectroscopic techniques have been widely used as diagnostic tools in the discrimination of many types of malignant diseases. Recently, synchronous fluorescent spectroscopy (SFS) coupled with chemometrics has been applied in cancer diagnostics. The SFS method involves simultaneous scanning of both emission and excitation wavelengths while keeping the interval of wavelengths (constant-wavelength mode) or frequencies (constant-energy mode) between them constant. This method is fast, relatively inexpensive, sensitive and non-invasive. Total synchronous fluorescence spectra of normal skin, nevus and melanoma samples were used as input for training of artificial neural networks. Two different types of artificial neural networks were trained, the self-organizing map and the feed-forward neural network. Histopathology results of investigated skin samples were used as the gold standard for network output. Based on the obtained classification success rate of neural networks, we concluded that both networks provided high sensitivity with classification errors between 2 and 4%. (paper)

NEpiC: a network-assisted algorithm for epigenetic studies using mean and variance combined signals.

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Ruan, Peifeng; Shen, Jing; Santella, Regina M; Zhou, Shuigeng; Wang, Shuang

2016-09-19

DNA methylation plays an important role in many biological processes. Existing epigenome-wide association studies (EWAS) have successfully identified aberrantly methylated genes in many diseases and disorders with most studies focusing on analysing methylation sites one at a time. Incorporating prior biological information such as biological networks has been proven to be powerful in identifying disease-associated genes in both gene expression studies and genome-wide association studies (GWAS) but has been under studied in EWAS. Although recent studies have noticed that there are differences in methylation variation in different groups, only a few existing methods consider variance signals in DNA methylation studies. Here, we present a network-assisted algorithm, NEpiC, that combines both mean and variance signals in searching for differentially methylated sub-networks using the protein-protein interaction (PPI) network. In simulation studies, we demonstrate the power gain from using both the prior biological information and variance signals compared to using either of the two or neither information. Applications to several DNA methylation datasets from the Cancer Genome Atlas (TCGA) project and DNA methylation data on hepatocellular carcinoma (HCC) from the Columbia University Medical Center (CUMC) suggest that the proposed NEpiC algorithm identifies more cancer-related genes and generates better replication results. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

[German national second-opinion network for testicular cancer and penile carcinoma : Two sources for evidence-based information].

Science.gov (United States)

Schrader, M; Zengerling, F; Hakenberg, O W; Protzel, C

2016-09-01

The second-opinion network for testicular cancer is an internet-based platform addressing physicians treating testicular cancer patients. They are offered a second-opinion before determining further therapy after orchiectomy and completion of staging. The high rate of discrepancies between the first and second opinion in more than 30 % supports the assumption of a deficit in the implementation of treatment guidelines. In 2015, approximately 22 % of the newly diagnosed cases with testicular cancer in Germany were covered by this system. According to the present interim analysis, the second-opinion platform helps to avoid overtreatment of testicular cancer patients. The high acceptance of the project and the encouraging results of this interim analysis gave rise to considerations to apply the second-opinion model to penile carcinoma. Data from the UK and the Netherlands show that the second-opinion network for penile cancer could help to improve treatment standards and results in Germany. Current data and the intended further development of the system are discussed.

Automatic classification of ovarian cancer types from cytological images using deep convolutional neural networks.

Science.gov (United States)

Wu, Miao; Yan, Chuanbo; Liu, Huiqiang; Liu, Qian

2018-06-29

Ovarian cancer is one of the most common gynecologic malignancies. Accurate classification of ovarian cancer types (serous carcinoma, mucous carcinoma, endometrioid carcinoma, transparent cell carcinoma) is an essential part in the different diagnosis. Computer-aided diagnosis (CADx) can provide useful advice for pathologists to determine the diagnosis correctly. In our study, we employed a Deep Convolutional Neural Networks (DCNN) based on AlexNet to automatically classify the different types of ovarian cancers from cytological images. The DCNN consists of five convolutional layers, three max pooling layers, and two full reconnect layers. Then we trained the model by two group input data separately, one was original image data and the other one was augmented image data including image enhancement and image rotation. The testing results are obtained by the method of 10-fold cross-validation, showing that the accuracy of classification models has been improved from 72.76 to 78.20% by using augmented images as training data. The developed scheme was useful for classifying ovarian cancers from cytological images. © 2018 The Author(s).

[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.

Design principles for cancer therapy guided by changes in complexity of protein-protein interaction networks.

Science.gov (United States)

Benzekry, Sebastian; Tuszynski, Jack A; Rietman, Edward A; Lakka Klement, Giannoula

2015-05-28

The ever-increasing expanse of online bioinformatics data is enabling new ways to, not only explore the visualization of these data, but also to apply novel mathematical methods to extract meaningful information for clinically relevant analysis of pathways and treatment decisions. One of the methods used for computing topological characteristics of a space at different spatial resolutions is persistent homology. This concept can also be applied to network theory, and more specifically to protein-protein interaction networks, where the number of rings in an individual cancer network represents a measure of complexity. We observed a linear correlation of R = -0.55 between persistent homology and 5-year survival of patients with a variety of cancers. This relationship was used to predict the proteins within a protein-protein interaction network with the most impact on cancer progression. By re-computing the persistent homology after computationally removing an individual node (protein) from the protein-protein interaction network, we were able to evaluate whether such an inhibition would lead to improvement in patient survival. The power of this approach lied in its ability to identify the effects of inhibition of multiple proteins and in the ability to expose whether the effect of a single inhibition may be amplified by inhibition of other proteins. More importantly, we illustrate specific examples of persistent homology calculations, which correctly predict the survival benefit observed effects in clinical trials using inhibitors of the identified molecular target. We propose that computational approaches such as persistent homology may be used in the future for selection of molecular therapies in clinic. The technique uses a mathematical algorithm to evaluate the node (protein) whose inhibition has the highest potential to reduce network complexity. The greater the drop in persistent homology, the greater reduction in network complexity, and thus a larger

Keeping their world together--meanings and actions created through network-focused nursing in teenager and young adult cancer care.

Science.gov (United States)

Olsen, Pia Riis; Harder, Ingegerd

2009-01-01

In the transition between dependent childhood and independent young adulthood, teenagers and young adults (TYAs) are extremely vulnerable when diagnosed with cancer and while undergoing treatment. Nurses working on a youth unit for patients aged 15 to 22 years developed a nursing program that aims at supporting these young patients and their significant others to maintain, establish, and strengthen their social network during the treatment period. This article presents a grounded theory study that explored how the network-focused program was perceived by TYAs with cancer and their significant others. A theoretical account is presented on the meanings and actions that the inherent processes and interactions created. Twelve TYAs and 19 significant others participated. Data were generated through interviews, observations, and informal conversations. Embracing the program and building strength were the 2 subcategories that linked to a core concept of keeping their world together. The findings show that nurses are in a unique position to enhance and support the efforts of these young patients and their significant others in connecting with the social network that extends beyond the family and includes the wider social network.

Discrimination of liver cancer in cellular level based on backscatter micro-spectrum with PCA algorithm and BP neural network

Science.gov (United States)

Yang, Jing; Wang, Cheng; Cai, Gan; Dong, Xiaona

2016-10-01

The incidence and mortality rate of the primary liver cancer are very high and its postoperative metastasis and recurrence have become important factors to the prognosis of patients. Circulating tumor cells (CTC), as a new tumor marker, play important roles in the early diagnosis and individualized treatment. This paper presents an effective method to distinguish liver cancer based on the cellular scattering spectrum, which is a non-fluorescence technique based on the fiber confocal microscopic spectrometer. Combining the principal component analysis (PCA) with back propagation (BP) neural network were utilized to establish an automatic recognition model for backscatter spectrum of the liver cancer cells from blood cell. PCA was applied to reduce the dimension of the scattering spectral data which obtained by the fiber confocal microscopic spectrometer. After dimensionality reduction by PCA, a neural network pattern recognition model with 2 input layer nodes, 11 hidden layer nodes, 3 output nodes was established. We trained the network with 66 samples and also tested it. Results showed that the recognition rate of the three types of cells is more than 90%, the relative standard deviation is only 2.36%. The experimental results showed that the fiber confocal microscopic spectrometer combining with the algorithm of PCA and BP neural network can automatically identify the liver cancer cell from the blood cells. This will provide a better tool for investigating the metastasis of liver cancers in vivo, the biology metabolic characteristics of liver cancers and drug transportation. Additionally, it is obviously referential in practical application.

Deep convolutional neural network with transfer learning for rectum toxicity prediction in cervical cancer radiotherapy: a feasibility study

Science.gov (United States)

Zhen, Xin; Chen, Jiawei; Zhong, Zichun; Hrycushko, Brian; Zhou, Linghong; Jiang, Steve; Albuquerque, Kevin; Gu, Xuejun

2017-11-01

Better understanding of the dose-toxicity relationship is critical for safe dose escalation to improve local control in late-stage cervical cancer radiotherapy. In this study, we introduced a convolutional neural network (CNN) model to analyze rectum dose distribution and predict rectum toxicity. Forty-two cervical cancer patients treated with combined external beam radiotherapy (EBRT) and brachytherapy (BT) were retrospectively collected, including twelve toxicity patients and thirty non-toxicity patients. We adopted a transfer learning strategy to overcome the limited patient data issue. A 16-layers CNN developed by the visual geometry group (VGG-16) of the University of Oxford was pre-trained on a large-scale natural image database, ImageNet, and fine-tuned with patient rectum surface dose maps (RSDMs), which were accumulated EBRT  +  BT doses on the unfolded rectum surface. We used the adaptive synthetic sampling approach and the data augmentation method to address the two challenges, data imbalance and data scarcity. The gradient-weighted class activation maps (Grad-CAM) were also generated to highlight the discriminative regions on the RSDM along with the prediction model. We compare different CNN coefficients fine-tuning strategies, and compare the predictive performance using the traditional dose volume parameters, e.g. D 0.1/1/2cc, and the texture features extracted from the RSDM. Satisfactory prediction performance was achieved with the proposed scheme, and we found that the mean Grad-CAM over the toxicity patient group has geometric consistence of distribution with the statistical analysis result, which indicates possible rectum toxicity location. The evaluation results have demonstrated the feasibility of building a CNN-based rectum dose-toxicity prediction model with transfer learning for cervical cancer radiotherapy.

Decoding network dynamics in cancer

DEFF Research Database (Denmark)

Linding, Rune

2014-01-01

Biological systems are composed of highly dynamic and interconnected molecular networks that drive biological decision processes. The goal of network biology is to describe, quantify and predict the information flow and functional behaviour of living systems in a formal language and with an accur......Biological systems are composed of highly dynamic and interconnected molecular networks that drive biological decision processes. The goal of network biology is to describe, quantify and predict the information flow and functional behaviour of living systems in a formal language...... and with an accuracy that parallels our characterisation of other physical systems such as Jumbo-jets. Decades of targeted molecular and biological studies have led to numerous pathway models of developmental and disease related processes. However, so far no global models have been derived from pathways, capable...

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

Directory of Open Access Journals (Sweden)

Cielito C Reyes-Gibby

Full Text Available Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA, a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive and thymine degradation pathways (p = 1.06-08 were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis. The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67. In conclusion, gene network analysis identified novel molecules and

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

Science.gov (United States)

Reyes-Gibby, Cielito C; Melkonian, Stephanie C; Wang, Jian; Yu, Robert K; Shelburne, Samuel A; Lu, Charles; Gunn, Gary Brandon; Chambers, Mark S; Hanna, Ehab Y; Yeung, Sai-Ching J; Shete, Sanjay

2017-01-01

Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA), a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive) and thymine degradation pathways (p = 1.06-08) were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis). The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67). In conclusion, gene network analysis identified novel molecules and biological

Potential upstream regulators of cannabinoid receptor 1 signaling in prostate cancer: a Bayesian network analysis of data from a tissue microarray.

Science.gov (United States)

Häggström, Jenny; Cipriano, Mariateresa; Forshell, Linus Plym; Persson, Emma; Hammarsten, Peter; Stella, Nephi; Fowler, Christopher J

2014-08-01

The endocannabinoid system regulates cancer cell proliferation, and in prostate cancer a high cannabinoid CB1 receptor expression is associated with a poor prognosis. Down-stream mediators of CB1 receptor signaling in prostate cancer are known, but information on potential upstream regulators is lacking. Data from a well-characterized tumor tissue microarray were used for a Bayesian network analysis using the max-min hill-climbing method. In non-malignant tissue samples, a directionality of pEGFR (the phosphorylated form of the epidermal growth factor receptor) → CB1 receptors were found regardless as to whether the endocannabinoid metabolizing enzyme fatty acid amide hydrolase (FAAH) was included as a parameter. A similar result was found in the tumor tissue, but only when FAAH was included in the analysis. A second regulatory pathway, from the growth factor receptor ErbB2 → FAAH was also identified in the tumor samples. Transfection of AT1 prostate cancer cells with CB1 receptors induced a sensitivity to the growth-inhibiting effects of the CB receptor agonist CP55,940. The sensitivity was not dependent upon the level of receptor expression. Thus a high CB1 receptor expression alone does not drive the cells towards a survival phenotype in the presence of a CB receptor agonist. The data identify two potential regulators of the endocannabinoid system in prostate cancer and allow the construction of a model of a dysregulated endocannabinoid signaling network in this tumor. Further studies should be designed to test the veracity of the predictions of the network analysis in prostate cancer and other solid tumors. © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc.

No study left behind: a network meta-analysis in non-small-cell lung cancer demonstrating the importance of considering all relevant data.

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Hawkins, Neil; Scott, David A; Woods, Beth S; Thatcher, Nicholas

2009-09-01

To demonstrate the importance of considering all relevant indirect data in a network meta-analysis of treatments for non-small-cell lung cancer (NSCLC). A recent National Institute for Health and Clinical Excellence appraisal focussed on the indirect comparison of docetaxel with erlotinib in second-line treatment of NSCLC based on trials including a common comparator. We compared the results of this analysis to a network meta-analysis including other trials that formed a network of evidence. We also examined the importance of allowing for the correlations between the estimated treatment effects that can arise when analysing such networks. The analysis of the restricted network including only trials of docetaxel and erlotinib linked via the common placebo comparator produced an estimated mean hazard ratio (HR) for erlotinib compared with docetaxel of 1.55 (95% confidence interval [CI] 0.72-2.97). In contrast, the network meta-analysis produced an estimated HR for erlotinib compared with docetaxel of 0.83 (95% CI 0.65-1.06). Analyzing the wider network improved the precision of estimated treatment effects, altered their rankings and also allowed further treatments to be compared. Some of the estimated treatment effects from the wider network were highly correlated. This empirical example shows the importance of considering all potentially relevant data when comparing treatments. Care should therefore be taken to consider all relevant information, including correlations induced by the network of trial data, when comparing treatments.

Cervical cancer: a qualitative study on subjectivity, family, gender and health services.

Science.gov (United States)

Villafuerte, Blanca E Pelcastre; Gómez, Laura L Tirado; Betancourt, Alejandro Mohar; Cervantes, Malaquías López

2007-03-01

In 2002, cervical cancer was one of the leading causes of death in Mexico. Quantitative techniques allowed for the identification of socioeconomic, behavioral and biological characteristics that are part of its etiology. However such characteristics, are inadequate to explain sufficiently the role that emotions, family networks and socially-constructed categories such as gender play in the demand and utilization of health services for cervical cancer diagnosis and treatment and neither the timely undertaking of preventive actions, such as getting a PAP smear or seeking adequate and continuous treatment. A qualitative study was carried out to analyze the role of different social and cultural factors in the timely detection of cervical cancer. As part of a multi-level, multi-method research effort, this particular study was based on individual interviews with women diagnosed with cervical cancer (identified as the "cases"), their female friends and relatives (identified as the "controls") and the cases' husbands. The results showed that both: denial and fear are two important components that regulate the behavior of both the women and their partners. Women with a small support network may have limited opportunities for taking action in favor of their own health and wellbeing. Women tend not to worry about their health, in general and neither about cervical cancer in particular, as a consequence of their conceptualizations regarding their body and feminine identify - both of which are socially determined. Furthermore, it is necessary to improve the quality of information provided in health services.

CTD² Dashboard: a searchable web interface to connect validated results from the Cancer Target Discovery and Development Network* | Office of Cancer Genomics

Science.gov (United States)

The Cancer Target Discovery and Development (CTD2) Network aims to use functional genomics to accelerate the translation of high-throughput and high-content genomic and small-molecule data towards use in precision oncology.

Co-trained convolutional neural networks for automated detection of prostate cancer in multi-parametric MRI.

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Yang, Xin; Liu, Chaoyue; Wang, Zhiwei; Yang, Jun; Min, Hung Le; Wang, Liang; Cheng, Kwang-Ting Tim

2017-12-01

Multi-parameter magnetic resonance imaging (mp-MRI) is increasingly popular for prostate cancer (PCa) detection and diagnosis. However, interpreting mp-MRI data which typically contains multiple unregistered 3D sequences, e.g. apparent diffusion coefficient (ADC) and T2-weighted (T2w) images, is time-consuming and demands special expertise, limiting its usage for large-scale PCa screening. Therefore, solutions to computer-aided detection of PCa in mp-MRI images are highly desirable. Most recent advances in automated methods for PCa detection employ a handcrafted feature based two-stage classification flow, i.e. voxel-level classification followed by a region-level classification. This work presents an automated PCa detection system which can concurrently identify the presence of PCa in an image and localize lesions based on deep convolutional neural network (CNN) features and a single-stage SVM classifier. Specifically, the developed co-trained CNNs consist of two parallel convolutional networks for ADC and T2w images respectively. Each network is trained using images of a single modality in a weakly-supervised manner by providing a set of prostate images with image-level labels indicating only the presence of PCa without priors of lesions' locations. Discriminative visual patterns of lesions can be learned effectively from clutters of prostate and surrounding tissues. A cancer response map with each pixel indicating the likelihood to be cancerous is explicitly generated at the last convolutional layer of the network for each modality. A new back-propagated error E is defined to enforce both optimized classification results and consistent cancer response maps for different modalities, which help capture highly representative PCa-relevant features during the CNN feature learning process. The CNN features of each modality are concatenated and fed into a SVM classifier. For images which are classified to contain cancers, non-maximum suppression and adaptive

Genome-wide profiling of the PIWI-interacting RNA-mRNA regulatory networks in epithelial ovarian cancers.

Science.gov (United States)

Singh, Garima; Roy, Jyoti; Rout, Pratiti; Mallick, Bibekanand

2018-01-01

PIWI-interacting (piRNAs), ~23-36 nucleotide-long small non-coding RNAs (sncRNAs), earlier believed to be germline-specific, have now been identified in somatic cells, including cancer cells. These sncRNAs impact critical biological processes by fine-tuning gene expression at post-transcriptional and epigenetic levels. The expression of piRNAs in ovarian cancer, the most lethal gynecologic cancer is largely uncharted. In this study, we investigated the expression of PIWILs by qRT-PCR and western blotting and then identified piRNA transcriptomes in tissues of normal ovary and two most prevalent epithelial ovarian cancer subtypes, serous and endometrioid by small RNA sequencing. We detected 219, 256 and 234 piRNAs in normal ovary, endometrioid and serous ovarian cancer samples respectively. We observed piRNAs are encoded from various genomic regions, among which introns harbor the majority of them. Surprisingly, piRNAs originated from different genomic contexts showed the varied level of conservations across vertebrates. The functional analysis of predicted targets of differentially expressed piRNAs revealed these could modulate key processes and pathways involved in ovarian oncogenesis. Our study provides the first comprehensive piRNA landscape in these samples and a useful resource for further functional studies to decipher new mechanistic views of piRNA-mediated gene regulatory networks affecting ovarian oncogenesis. The RNA-seq data is submitted to GEO database (GSE83794).

MET network in PubMed: a text-mined network visualization and curation system.

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Dai, Hong-Jie; Su, Chu-Hsien; Lai, Po-Ting; Huang, Ming-Siang; Jonnagaddala, Jitendra; Rose Jue, Toni; Rao, Shruti; Chou, Hui-Jou; Milacic, Marija; Singh, Onkar; Syed-Abdul, Shabbir; Hsu, Wen-Lian

2016-01-01

Metastasis is the dissemination of a cancer/tumor from one organ to another, and it is the most dangerous stage during cancer progression, causing more than 90% of cancer deaths. Improving the understanding of the complicated cellular mechanisms underlying metastasis requires investigations of the signaling pathways. To this end, we developed a METastasis (MET) network visualization and curation tool to assist metastasis researchers retrieve network information of interest while browsing through the large volume of studies in PubMed. MET can recognize relations among genes, cancers, tissues and organs of metastasis mentioned in the literature through text-mining techniques, and then produce a visualization of all mined relations in a metastasis network. To facilitate the curation process, MET is developed as a browser extension that allows curators to review and edit concepts and relations related to metastasis directly in PubMed. PubMed users can also view the metastatic networks integrated from the large collection of research papers directly through MET. For the BioCreative 2015 interactive track (IAT), a curation task was proposed to curate metastatic networks among PubMed abstracts. Six curators participated in the proposed task and a post-IAT task, curating 963 unique metastatic relations from 174 PubMed abstracts using MET.Database URL: http://btm.tmu.edu.tw/metastasisway. © The Author(s) 2016. Published by Oxford University Press.

Research in Danish cancer rehabilitation

DEFF Research Database (Denmark)

Høybye, Mette Terp; Dalton, Susanne Oksbjerg; Christensen, Jane

2008-01-01

rate at baseline was 86% (n = 1876). Most participants were younger women with breast cancer. They were generally well educated and working. The cancer survivors reported having comprehensive social networks and being physically active. Several cancer-related symptoms were reported by women...... site, sex, age, family, working status and social position. These challenges might be addressed optimally in multi-dimensional rehabilitation programmes....... of the cancer survivors with respect to cancer site, sociodemographic variables, social network, lifestyle, self-rated health and the prevalence of cancer-related late effects. The study is part of the FOCARE research project, in which the long-term effects of the rehabilitation programme are evaluated...

A Bayesian network meta-analysis on second-line systemic therapy in advanced gastric cancer.

Science.gov (United States)

Zhu, Xiaofu; Ko, Yoo-Joung; Berry, Scott; Shah, Keya; Lee, Esther; Chan, Kelvin

2017-07-01

It is unclear which regimen is the most efficacious among the available therapies for advanced gastric cancer in the second-line setting. We performed a network meta-analysis to determine their relative benefits. We conducted a systematic review of randomized controlled trials (RCTs) through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and American Society of Clinical Oncology abstracts up to June 2014 to identify phase III RCTs on advanced gastric cancer in the second-line setting. Overall survival (OS) data were the primary outcome of interest. Hazard ratios (HRs) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods. A Bayesian network meta-analysis was performed with WinBUGS to compare all regimens simultaneously. Eight RCTs (2439 patients) were identified and contained extractable data for quantitative analysis. Network meta-analysis showed that paclitaxel plus ramucirumab was superior to single-agent ramucirumab [OS HR 0.51, 95 % credible region (CR) 0.30-0.86], paclitaxel (OS HR 0.81, 95 % CR 0.68-0.96), docetaxel (OS HR 0.56, 95 % CR 0.33-0.94), and irinotecan (OS HR 0.71, 95 % CR 0.52-0.99). Paclitaxel plus ramucirumab also had an 89 % probability of being the best regimen among all these regimens. Single-agent ramucirumab, paclitaxel, docetaxel, and irinotecan were comparable to each other with respect to OS and were superior to best supportive care. This is the first network meta-analysis to compare all second-line regimens reported in phase III gastric cancer trials. The results suggest the paclitaxel plus ramucirumab combination is the most effective therapy and should be the reference regimen for future comparative trials.

Usage of Probabilistic and General Regression Neural Network for Early Detection and Prevention of Oral Cancer

Directory of Open Access Journals (Sweden)

Neha Sharma

2015-01-01

Full Text Available In India, the oral cancers are usually presented in advanced stage of malignancy. It is critical to ascertain the diagnosis in order to initiate most advantageous treatment of the suspicious lesions. The main hurdle in appropriate treatment and control of oral cancer is identification and risk assessment of early disease in the community in a cost-effective fashion. The objective of this research is to design a data mining model using probabilistic neural network and general regression neural network (PNN/GRNN for early detection and prevention of oral malignancy. The model is built using the oral cancer database which has 35 attributes and 1025 records. All the attributes pertaining to clinical symptoms and history are considered to classify malignant and non-malignant cases. Subsequently, the model attempts to predict particular type of cancer, its stage and extent with the help of attributes pertaining to symptoms, gross examination and investigations. Also, the model envisages anticipating the survivability of a patient on the basis of treatment and follow-up details. Finally, the performance of the PNN/GRNN model is compared with that of other classification models. The classification accuracy of PNN/GRNN model is 80% and hence is better for early detection and prevention of the oral cancer.

Usage of Probabilistic and General Regression Neural Network for Early Detection and Prevention of Oral Cancer.

Science.gov (United States)

Sharma, Neha; Om, Hari

2015-01-01

In India, the oral cancers are usually presented in advanced stage of malignancy. It is critical to ascertain the diagnosis in order to initiate most advantageous treatment of the suspicious lesions. The main hurdle in appropriate treatment and control of oral cancer is identification and risk assessment of early disease in the community in a cost-effective fashion. The objective of this research is to design a data mining model using probabilistic neural network and general regression neural network (PNN/GRNN) for early detection and prevention of oral malignancy. The model is built using the oral cancer database which has 35 attributes and 1025 records. All the attributes pertaining to clinical symptoms and history are considered to classify malignant and non-malignant cases. Subsequently, the model attempts to predict particular type of cancer, its stage and extent with the help of attributes pertaining to symptoms, gross examination and investigations. Also, the model envisages anticipating the survivability of a patient on the basis of treatment and follow-up details. Finally, the performance of the PNN/GRNN model is compared with that of other classification models. The classification accuracy of PNN/GRNN model is 80% and hence is better for early detection and prevention of the oral cancer.

A network-based gene expression signature informs prognosis and treatment for colorectal cancer patients.

Directory of Open Access Journals (Sweden)

Mingguang Shi

Full Text Available Several studies have reported gene expression signatures that predict recurrence risk in stage II and III colorectal cancer (CRC patients with minimal gene membership overlap and undefined biological relevance. The goal of this study was to investigate biological themes underlying these signatures, to infer genes of potential mechanistic importance to the CRC recurrence phenotype and to test whether accurate prognostic models can be developed using mechanistically important genes.We investigated eight published CRC gene expression signatures and found no functional convergence in Gene Ontology enrichment analysis. Using a random walk-based approach, we integrated these signatures and publicly available somatic mutation data on a protein-protein interaction network and inferred 487 genes that were plausible candidate molecular underpinnings for the CRC recurrence phenotype. We named the list of 487 genes a NEM signature because it integrated information from Network, Expression, and Mutation. The signature showed significant enrichment in four biological processes closely related to cancer pathophysiology and provided good coverage of known oncogenes, tumor suppressors, and CRC-related signaling pathways. A NEM signature-based Survival Support Vector Machine prognostic model was trained using a microarray gene expression dataset and tested on an independent dataset. The model-based scores showed a 75.7% concordance with the real survival data and separated patients into two groups with significantly different relapse-free survival (p = 0.002. Similar results were obtained with reversed training and testing datasets (p = 0.007. Furthermore, adjuvant chemotherapy was significantly associated with prolonged survival of the high-risk patients (p = 0.006, but not beneficial to the low-risk patients (p = 0.491.The NEM signature not only reflects CRC biology but also informs patient prognosis and treatment response. Thus, the network

Histopathological Breast Cancer Image Classification by Deep Neural Network Techniques Guided by Local Clustering.

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Nahid, Abdullah-Al; Mehrabi, Mohamad Ali; Kong, Yinan

2018-01-01

Breast Cancer is a serious threat and one of the largest causes of death of women throughout the world. The identification of cancer largely depends on digital biomedical photography analysis such as histopathological images by doctors and physicians. Analyzing histopathological images is a nontrivial task, and decisions from investigation of these kinds of images always require specialised knowledge. However, Computer Aided Diagnosis (CAD) techniques can help the doctor make more reliable decisions. The state-of-the-art Deep Neural Network (DNN) has been recently introduced for biomedical image analysis. Normally each image contains structural and statistical information. This paper classifies a set of biomedical breast cancer images (BreakHis dataset) using novel DNN techniques guided by structural and statistical information derived from the images. Specifically a Convolutional Neural Network (CNN), a Long-Short-Term-Memory (LSTM), and a combination of CNN and LSTM are proposed for breast cancer image classification. Softmax and Support Vector Machine (SVM) layers have been used for the decision-making stage after extracting features utilising the proposed novel DNN models. In this experiment the best Accuracy value of 91.00% is achieved on the 200x dataset, the best Precision value 96.00% is achieved on the 40x dataset, and the best F -Measure value is achieved on both the 40x and 100x datasets.

Construction and analysis of protein-protein interaction networks based on proteomics data of prostate cancer

Science.gov (United States)

CHEN, CHEN; SHEN, HONG; ZHANG, LI-GUO; LIU, JIAN; CAO, XIAO-GE; YAO, AN-LIANG; KANG, SHAO-SAN; GAO, WEI-XING; HAN, HUI; CAO, FENG-HONG; LI, ZHI-GUO

2016-01-01

Currently, using human prostate cancer (PCa) tissue samples to conduct proteomics research has generated a large amount of data; however, only a very small amount has been thoroughly investigated. In this study, we manually carried out the mining of the full text of proteomics literature that involved comparisons between PCa and normal or benign tissue and identified 41 differentially expressed proteins verified or reported more than 2 times from different research studies. We regarded these proteins as seed proteins to construct a protein-protein interaction (PPI) network. The extended network included one giant network, which consisted of 1,264 nodes connected via 1,744 edges, and 3 small separate components. The backbone network was then constructed, which was derived from key nodes and the subnetwork consisting of the shortest path between seed proteins. Topological analyses of these networks were conducted to identify proteins essential for the genesis of PCa. Solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4) had the highest closeness centrality located in the center of each network, and the highest betweenness centrality and largest degree in the backbone network. Tubulin, beta 2C (TUBB2C) had the largest degree in the giant network and subnetwork. In addition, using module analysis of the whole PPI network, we obtained a densely connected region. Functional annotation indicated that the Ras protein signal transduction biological process, mitogen-activated protein kinase (MAPK), neurotrophin and the gonadotropin-releasing hormone (GnRH) signaling pathway may play an important role in the genesis and development of PCa. Further investigation of the SLC2A4, TUBB2C proteins, and these biological processes and pathways may therefore provide a potential target for the diagnosis and treatment of PCa. PMID:27121963

Network analysis of ChIP-Seq data reveals key genes in prostate cancer.

Science.gov (United States)

Zhang, Yu; Huang, Zhen; Zhu, Zhiqiang; Liu, Jianwei; Zheng, Xin; Zhang, Yuhai

2014-09-03

Prostate cancer (PC) is the second most common cancer among men in the United States, and it imposes a considerable threat to human health. A deep understanding of its underlying molecular mechanisms is the premise for developing effective targeted therapies. Recently, deep transcriptional sequencing has been used as an effective genomic assay to obtain insights into diseases and may be helpful in the study of PC. In present study, ChIP-Seq data for PC and normal samples were compared, and differential peaks identified, based upon fold changes (with P-values calculated with t-tests). Annotations of these peaks were performed. Protein-protein interaction (PPI) network analysis was performed with BioGRID and constructed with Cytoscape, following which the highly connected genes were screened. We obtained a total of 5,570 differential peaks, including 3,726 differentially enriched peaks in tumor samples and 1,844 differentially enriched peaks in normal samples. There were eight significant regions of the peaks. The intergenic region possessed the highest score (51%), followed by intronic (31%) and exonic (11%) regions. The analysis revealed the top 35 highly connected genes, which comprised 33 differential genes (such as YWHAQ, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein and θ polypeptide) from ChIP-Seq data and 2 differential genes retrieved from the PPI network: UBA52 (ubiquitin A-52 residue ribosomal protein fusion product (1) and SUMO2 (SMT3 suppressor of mif two 3 homolog (2) . Our findings regarding potential PC-related genes increase the understanding of PC and provides direction for future research.

Robustness and backbone motif of a cancer network regulated by miR-17-92 cluster during the G1/S transition.

Directory of Open Access Journals (Sweden)

Lijian Yang

Full Text Available Based on interactions among transcription factors, oncogenes, tumor suppressors and microRNAs, a Boolean model of cancer network regulated by miR-17-92 cluster is constructed, and the network is associated with the control of G1/S transition in the mammalian cell cycle. The robustness properties of this regulatory network are investigated by virtue of the Boolean network theory. It is found that, during G1/S transition in the cell cycle process, the regulatory networks are robustly constructed, and the robustness property is largely preserved with respect to small perturbations to the network. By using the unique process-based approach, the structure of this network is analyzed. It is shown that the network can be decomposed into a backbone motif which provides the main biological functions, and a remaining motif which makes the regulatory system more stable. The critical role of miR-17-92 in suppressing the G1/S cell cycle checkpoint and increasing the uncontrolled proliferation of the cancer cells by targeting a genetic network of interacting proteins is displayed with our model.

Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival.

Science.gov (United States)

Megchelenbrink, Wout; Katzir, Rotem; Lu, Xiaowen; Ruppin, Eytan; Notebaart, Richard A

2015-09-29

Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.

Cervical cancer: a qualitative study on subjectivity, family, gender and health services

Directory of Open Access Journals (Sweden)

López-Cervantes Malaquías

2007-03-01

Full Text Available Abstract Background In 2002, cervical cancer was one of the leading causes of death in Mexico. Quantitative techniques allowed for the identification of socioeconomic, behavioral and biological characteristics that are part of its etiology. However such characteristics, are inadequate to explain sufficiently the role that emotions, family networks and socially-constructed categories such as gender play in the demand and utilization of health services for cervical cancer diagnosis and treatment and neither the timely undertaking of preventive actions, such as getting a PAP smear or seeking adequate and continuons treatment. Methods A qualitative study was carried out to analyze the role of different social and cultural factors in the timely detection of cervical cancer. As part of a multi-level, multi-method research effort, this particular study was based on individual interviews with women diagnosed with cervical cancer (identified as the "cases", their female friends and relatives (identified as the "controls" and the cases' husbands. Results The results showed that both: denial and fear are two important components that regulate the behavior of both the women and their partners. Women with a small support network may have limited opportunities for taking action in favor of their own health and wellbeing. Conclusion Women tend not to worry about their health, in general and neither about cervical cancer in particular, as a consequence of their conceptualizations regarding their body and feminine identify – both of which are socially determined. Furthermore, it is necessary to improve the quality of information provided in health services.

Bayesian network modelling on data from fine needle aspiration cytology examination for breast cancer diagnosis

OpenAIRE

Ding, Xuemei; Cao, Yi; Zhai, Jia; Maguire, Liam; Li, Yuhua; Yang, Hongqin; Wang, Yuhua; Zeng, Jinshu; Liu, Shuo

2017-01-01

The paper employed Bayesian network (BN) modelling approach to discover causal dependencies among different data features of Breast Cancer Wisconsin Dataset (BCWD) derived from openly sourced UCI repository. K2 learning algorithm and k-fold cross validation were used to construct and optimize BN structure. Compared to Na‹ve Bayes (NB), the obtained BN presented better performance for breast cancer diagnosis based on fine needle aspiration cytology (FNAC) examination. It also showed that, amon...

Awareness and uptake of direct-to-consumer genetic testing among cancer cases, their relatives, and controls: the Northwest Cancer Genetics Network.

Science.gov (United States)

Hall, Taryn O; Renz, Anne D; Snapinn, Katherine W; Bowen, Deborah J; Edwards, Karen L

2012-07-01

To determine if awareness of, interest in, and use of direct-to-consumer (DTC) genetic testing is greater in a sample of high-risk individuals (cancer cases and their relatives), compared to controls. Participants were recruited from the Northwest Cancer Genetics Network. A follow-up survey was mailed to participants to assess DTC genetic testing awareness, interest, and use. One thousand two hundred sixty-seven participants responded to the survey. Forty-nine percent of respondents were aware of DTC genetic testing. Of those aware, 19% indicated interest in obtaining and testing. Additional information supplied by respondents who reported use of DTC genetic tests indicated that 55% of these respondents likely engaged in clinical genetic testing, rather than DTC genetic testing. Awareness of DTC genetic testing was greater in our sample of high-risk individuals than in controls and population-based studies. Although interest in and use of these tests among cases in our sample were equivalent to other population-based studies, interest in testing was higher among relatives and people who self-referred for a registry focused on cancer than among cases and controls. Additionally, our results suggest that there may be some confusion about what constitutes DTC genetic testing.

The Cervix Cancer Research Network (CCRN: Increasing access to cancer clinical trials in low- and middle-income countries

Directory of Open Access Journals (Sweden)

Gita eSuneja

2015-02-01

Full Text Available Introduction: The burden of cervical cancer is large and growing in developing countries, due in large part to limited access to screening services and lack of human papillomavirus (HPV vaccination. In spite of modern advances in diagnostic and therapeutic modalities, outcomes from cervical cancer have not markedly improved in recent years. Novel clinical trials are urgently needed to improve outcomes from cervical cancer worldwide. Methods: The Cervix Cancer Research Network (CCRN, a subsidiary of the Gynecologic Cancer InterGroup (GCIG, is a multi-national, multi-institutional consortium of physicians and scientists focused on improving cervical cancer outcomes worldwide by making cancer clinical trials available in low-, middle-, and high-income countries. Standard operating procedures for participation in CCRN include a pre-qualifying questionnaire to evaluate clinical activities and research infrastructure, followed by a site visit. Once a site is approved, they may choose to participate in one of four currently accruing clinical trials.Results: To date, 13 different CCRN site visits have been performed. Of these 13 sites visited, 10 have been approved as CCRN sites including Tata Memorial Hospital, India; Bangalore, India; Trivandrum, India; Ramathibodi, Thailand; Siriaj, Thailand; Pramongkutklao, Thailand; Ho Chi Minh, Vietnam; Blokhin Russian Cancer Research Center; the Hertzen Moscow Cancer Research Institute; and the Russian Scientific Center of Roentgenoradiology. The four currently accruing clinical trials are TACO, OUTBACK, INTERLACE, and SHAPE.Discussion: The CCRN has successfully enrolled 10 sites in developing countries to participate in four randomized clinical trials. The primary objectives are to provide novel therapeutics to regions with the greatest need and to improve the validity and generalizability of clinical trial results by enrolling a diverse sample of patients.

Networked Microgrids Scoping Study

Energy Technology Data Exchange (ETDEWEB)

Backhaus, Scott N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dobriansky, Larisa [General MicroGrids, San Diego, CA (United States); Glover, Steve [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Liu, Chen-Ching [Washington State Univ., Pullman, WA (United States); Looney, Patrick [Brookhaven National Lab. (BNL), Upton, NY (United States); Mashayekh, Salman [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Pratt, Annabelle [National Renewable Energy Lab. (NREL), Golden, CO (United States); Schneider, Kevin [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Stadler, Michael [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Starke, Michael [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Wang, Jianhui [Argonne National Lab. (ANL), Argonne, IL (United States); Yue, Meng [Brookhaven National Lab. (BNL), Upton, NY (United States)

2016-12-05

Much like individual microgrids, the range of opportunities and potential architectures of networked microgrids is very diverse. The goals of this scoping study are to provide an early assessment of research and development needs by examining the benefits of, risks created by, and risks to networked microgrids. At this time there are very few, if any, examples of deployed microgrid networks. In addition, there are very few tools to simulate or otherwise analyze the behavior of networked microgrids. In this setting, it is very difficult to evaluate networked microgrids systematically or quantitatively. At this early stage, this study is relying on inputs, estimations, and literature reviews by subject matter experts who are engaged in individual microgrid research and development projects, i.e., the authors of this study The initial step of the study gathered input about the potential opportunities provided by networked microgrids from these subject matter experts. These opportunities were divided between the subject matter experts for further review. Part 2 of this study is comprised of these reviews. Part 1 of this study is a summary of the benefits and risks identified in the reviews in Part 2 and synthesis of the research needs required to enable networked microgrids.

LSD1 activates a lethal prostate cancer gene network independently of its demethylase function.

Science.gov (United States)

Sehrawat, Archana; Gao, Lina; Wang, Yuliang; Bankhead, Armand; McWeeney, Shannon K; King, Carly J; Schwartzman, Jacob; Urrutia, Joshua; Bisson, William H; Coleman, Daniel J; Joshi, Sunil K; Kim, Dae-Hwan; Sampson, David A; Weinmann, Sheila; Kallakury, Bhaskar V S; Berry, Deborah L; Haque, Reina; Van Den Eeden, Stephen K; Sharma, Sunil; Bearss, Jared; Beer, Tomasz M; Thomas, George V; Heiser, Laura M; Alumkal, Joshi J

2018-05-01

Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need to develop new treatments targeting molecular pathways enriched in lethal prostate cancer. Lysine-specific demethylase 1 (LSD1) is a histone demethylase and an important regulator of gene expression. Here, we show that LSD1 promotes the survival of prostate cancer cells, including those that are castration-resistant, independently of its demethylase function and of the AR. Importantly, this effect is explained in part by activation of a lethal prostate cancer gene network in collaboration with LSD1's binding protein, ZNF217. Finally, that a small-molecule LSD1 inhibitor-SP-2509-blocks important demethylase-independent functions and suppresses castration-resistant prostate cancer cell viability demonstrates the potential of LSD1 inhibition in this disease.

Vietnamese American women’s beliefs and perceptions on cervical cancer, cervical cancer screening, and cancer prevention vaccines: A community-based participatory study

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Connie Kim Yen Nguyen-Truong

2017-12-01

Full Text Available Cervical cancer remains commonly diagnosed in Vietnamese American women. Despite efforts to increase cervical cancer screening among Vietnamese American women, participation rates are persistently lower than the national goal. The objective of this study is to explore beliefs of Vietnamese American women about cervical cancer, cervical cancer screening, and cancer prevention vaccines. A qualitative descriptive investigation captured group perceptions about meaning and beliefs of cervical cancer, screening, and cancer prevention vaccines, and participants’ stories using a community-based participatory research approach. Forty Vietnamese American women were recruited from the Portland, Oregon metropolitan area into four focus groups. Using a process of directed content analysis, focus group transcripts were coded for themes. We found that cervical cancer continues to be a difficult topic to discuss, and Vietnamese American women may not bring the topic up themselves to their health care providers. Some women experienced intense emotions of fear or shame of having their cervix examined. Women delayed seeking cervical cancer screening and needed to have early warning signs, which guided them as to when to seek health care. Women focused on cleanliness through vaginal and/or perineal washing as primary prevention for cervical cancer. There were limited awareness and knowledge about cancer prevention vaccines, specifically the human papillomavirus. Some women relied heavily on their informal social networks of family, friends, or community for health knowledge. Fear and misunderstanding dominated the beliefs of Vietnamese American women about cervical cancer screening and prevention. These findings underscored the importance of having culturally-specific findings, which will inform a multicomponent intervention to promote cervical cancer screening and cancer prevention vaccine uptake within this population.

Type 2 diabetes mellitus is associated with increased risk of pancreatic cancer: A veteran administration registry study

OpenAIRE

Makhoul, Issam; Yacoub, Abdulraheem; Siegel, Eric

2016-01-01

Background: The etiology of pancreatic cancer remains elusive. Several studies have suggested a role for diabetes mellitus, but the magnitude of its contribution remains controversial. Objectives: Utilizing a large administrative database, this retrospective cohort study was designed to investigate the relationship between type 2 diabetes mellitus and pancreatic cancer. Patients and design: Using the Veterans Integrated Services Network 16 database, 322,614 subjects were enrolled in the study...

Predicting Genes Involved in Human Cancer Using Network Contextual Information

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Rahmani Hossein

2012-03-01

Full Text Available Protein-Protein Interaction (PPI networks have been widely used for the task of predicting proteins involved in cancer. Previous research has shown that functional information about the protein for which a prediction is made, proximity to specific other proteins in the PPI network, as well as local network structure are informative features in this respect. In this work, we introduce two new types of input features, reflecting additional information: (1 Functional Context: the functions of proteins interacting with the target protein (rather than the protein itself; and (2 Structural Context: the relative position of the target protein with respect to specific other proteins selected according to a novel ANOVA (analysis of variance based measure. We also introduce a selection strategy to pinpoint the most informative features. Results show that the proposed feature types and feature selection strategy yield informative features. A standard machine learning method (Naive Bayes that uses the features proposed here outperforms the current state-of-the-art methods by more than 5% with respect to F-measure. In addition, manual inspection confirms the biological relevance of the top-ranked features.

In-Silico Integration Approach to Identify a Key miRNA Regulating a Gene Network in Aggressive Prostate Cancer

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Colaprico, Antonio; Bontempi, Gianluca; Castiglioni, Isabella

2018-01-01

Like other cancer diseases, prostate cancer (PC) is caused by the accumulation of genetic alterations in the cells that drives malignant growth. These alterations are revealed by gene profiling and copy number alteration (CNA) analysis. Moreover, recent evidence suggests that also microRNAs have an important role in PC development. Despite efforts to profile PC, the alterations (gene, CNA, and miRNA) and biological processes that correlate with disease development and progression remain partially elusive. Many gene signatures proposed as diagnostic or prognostic tools in cancer poorly overlap. The identification of co-expressed genes, that are functionally related, can identify a core network of genes associated with PC with a better reproducibility. By combining different approaches, including the integration of mRNA expression profiles, CNAs, and miRNA expression levels, we identified a gene signature of four genes overlapping with other published gene signatures and able to distinguish, in silico, high Gleason-scored PC from normal human tissue, which was further enriched to 19 genes by gene co-expression analysis. From the analysis of miRNAs possibly regulating this network, we found that hsa-miR-153 was highly connected to the genes in the network. Our results identify a four-gene signature with diagnostic and prognostic value in PC and suggest an interesting gene network that could play a key regulatory role in PC development and progression. Furthermore, hsa-miR-153, controlling this network, could be a potential biomarker for theranostics in high Gleason-scored PC. PMID:29562723

Gene network inherent in genomic big data improves the accuracy of prognostic prediction for cancer patients.

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Kim, Yun Hak; Jeong, Dae Cheon; Pak, Kyoungjune; Goh, Tae Sik; Lee, Chi-Seung; Han, Myoung-Eun; Kim, Ji-Young; Liangwen, Liu; Kim, Chi Dae; Jang, Jeon Yeob; Cha, Wonjae; Oh, Sae-Ock

2017-09-29

Accurate prediction of prognosis is critical for therapeutic decisions regarding cancer patients. Many previously developed prognostic scoring systems have limitations in reflecting recent progress in the field of cancer biology such as microarray, next-generation sequencing, and signaling pathways. To develop a new prognostic scoring system for cancer patients, we used mRNA expression and clinical data in various independent breast cancer cohorts (n=1214) from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and Gene Expression Omnibus (GEO). A new prognostic score that reflects gene network inherent in genomic big data was calculated using Network-Regularized high-dimensional Cox-regression (Net-score). We compared its discriminatory power with those of two previously used statistical methods: stepwise variable selection via univariate Cox regression (Uni-score) and Cox regression via Elastic net (Enet-score). The Net scoring system showed better discriminatory power in prediction of disease-specific survival (DSS) than other statistical methods (p=0 in METABRIC training cohort, p=0.000331, 4.58e-06 in two METABRIC validation cohorts) when accuracy was examined by log-rank test. Notably, comparison of C-index and AUC values in receiver operating characteristic analysis at 5 years showed fewer differences between training and validation cohorts with the Net scoring system than other statistical methods, suggesting minimal overfitting. The Net-based scoring system also successfully predicted prognosis in various independent GEO cohorts with high discriminatory power. In conclusion, the Net-based scoring system showed better discriminative power than previous statistical methods in prognostic prediction for breast cancer patients. This new system will mark a new era in prognosis prediction for cancer patients.

Use of an Artificial Neural Network to Construct a Model of Predicting Deep Fungal Infection in Lung Cancer Patients.

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Chen, Jian; Chen, Jie; Ding, Hong-Yan; Pan, Qin-Shi; Hong, Wan-Dong; Xu, Gang; Yu, Fang-You; Wang, Yu-Min

2015-01-01

The statistical methods to analyze and predict the related dangerous factors of deep fungal infection in lung cancer patients were several, such as logic regression analysis, meta-analysis, multivariate Cox proportional hazards model analysis, retrospective analysis, and so on, but the results are inconsistent. A total of 696 patients with lung cancer were enrolled. The factors were compared employing Student's t-test or the Mann-Whitney test or the Chi-square test and variables that were significantly related to the presence of deep fungal infection selected as candidates for input into the final artificial neural network analysis (ANN) model. The receiver operating characteristic (ROC) and area under curve (AUC) were used to evaluate the performance of the artificial neural network (ANN) model and logistic regression (LR) model. The prevalence of deep fungal infection from lung cancer in this entire study population was 32.04%(223/696), deep fungal infections occur in sputum specimens 44.05% (200/454). The ratio of candida albicans was 86.99% (194/223) in the total fungi. It was demonstrated that older (≥65 years), use of antibiotics, low serum albumin concentrations (≤37.18 g /L), radiotherapy, surgery, low hemoglobin hyperlipidemia (≤93.67 g /L), long time of hospitalization (≥14 days) were apt to deep fungal infection and the ANN model consisted of the seven factors. The AUC of ANN model (0.829±0.019) was higher than that of LR model (0.756±0.021). The artificial neural network model with variables consisting of age, use of antibiotics, serum albumin concentrations, received radiotherapy, received surgery, hemoglobin, time of hospitalization should be useful for predicting the deep fungal infection in lung cancer.

A Critical Evaluation of Network and Pathway-Based Classifiers for Outcome Prediction in Breast Cancer

NARCIS (Netherlands)

C. Staiger (Christine); S. Cadot; R Kooter; M. Dittrich (Marcus); T. Müller (Tobias); G.W. Klau (Gunnar); L.F.A. Wessels (Lodewyk)

2012-01-01

htmlabstractRecently, several classifiers that combine primary tumor data, like gene expression data, and secondary data sources, such as protein-protein interaction networks, have been proposed for predicting outcome in breast cancer. In these approaches, new composite features are typically

Predicting the Survival of Gastric Cancer Patients Using

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Korhani Kangi, Azam; Bahrampour, Abbas

2018-02-26

Introduction and purpose: In recent years the use of neural networks without any premises for investigation of prognosis in analyzing survival data has increased. Artificial neural networks (ANN) use small processors with a continuous network to solve problems inspired by the human brain. Bayesian neural networks (BNN) constitute a neural-based approach to modeling and non-linearization of complex issues using special algorithms and statistical methods. Gastric cancer incidence is the first and third ranking for men and women in Iran, respectively. The aim of the present study was to assess the value of an artificial neural network and a Bayesian neural network for modeling and predicting of probability of gastric cancer patient death. Materials and Methods: In this study, we used information on 339 patients aged from 20 to 90 years old with positive gastric cancer, referred to Afzalipoor and Shahid Bahonar Hospitals in Kerman City from 2001 to 2015. The three layers perceptron neural network (ANN) and the Bayesian neural network (BNN) were used for predicting the probability of mortality using the available data. To investigate differences between the models, sensitivity, specificity, accuracy and the area under receiver operating characteristic curves (AUROCs) were generated. Results: In this study, the sensitivity and specificity of the artificial neural network and Bayesian neural network models were 0.882, 0.903 and 0.954, 0.909, respectively. Prediction accuracy and the area under curve ROC for the two models were 0.891, 0.944 and 0.935, 0.961. The age at diagnosis of gastric cancer was most important for predicting survival, followed by tumor grade, morphology, gender, smoking history, opium consumption, receiving chemotherapy, presence of metastasis, tumor stage, receiving radiotherapy, and being resident in a village. Conclusion: The findings of the present study indicated that the Bayesian neural network is preferable to an artificial neural network for

Gene expression patterns combined with network analysis identify hub genes associated with bladder cancer.

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Bi, Dongbin; Ning, Hao; Liu, Shuai; Que, Xinxiang; Ding, Kejia

2015-06-01

To explore molecular mechanisms of bladder cancer (BC), network strategy was used to find biomarkers for early detection and diagnosis. The differentially expressed genes (DEGs) between bladder carcinoma patients and normal subjects were screened using empirical Bayes method of the linear models for microarray data package. Co-expression networks were constructed by differentially co-expressed genes and links. Regulatory impact factors (RIF) metric was used to identify critical transcription factors (TFs). The protein-protein interaction (PPI) networks were constructed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and clusters were obtained through molecular complex detection (MCODE) algorithm. Centralities analyses for complex networks were performed based on degree, stress and betweenness. Enrichment analyses were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Co-expression networks and TFs (based on expression data of global DEGs and DEGs in different stages and grades) were identified. Hub genes of complex networks, such as UBE2C, ACTA2, FABP4, CKS2, FN1 and TOP2A, were also obtained according to analysis of degree. In gene enrichment analyses of global DEGs, cell adhesion, proteinaceous extracellular matrix and extracellular matrix structural constituent were top three GO terms. ECM-receptor interaction, focal adhesion, and cell cycle were significant pathways. Our results provide some potential underlying biomarkers of BC. However, further validation is required and deep studies are needed to elucidate the pathogenesis of BC. Copyright © 2015 Elsevier Ltd. All rights reserved.

I Keep my Problems to Myself: Negative Social Network Orientation, Social Resources, and Health-Related Quality of Life in Cancer Survivors

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Symes, Yael; Campo, Rebecca A.; Wu, Lisa M.; Austin, Jane

2016-01-01

Background Cancer survivors treated with hematopoietic stem cell transplant rely on their social network for successful recovery. However, some survivors have negative attitudes about using social resources (negative social network orientation) that are critical for their recovery. Purpose We examined the association between survivors’ social network orientation and health-related quality of life (HRQoL) and whether it was mediated by social resources (network size, perceived support, and negative and positive support-related social exchanges). Methods In a longitudinal study, 255 survivors completed validated measures of social network orientation, HRQoL, and social resources. Hypotheses were tested using path analysis. Results More negative social network orientation predicted worse HRQoL (p social exchanges. Conclusions Survivors with negative social network orientation may have poorer HRQoL in part due to deficits in several key social resources. Findings highlight a subgroup at risk for poor transplant outcomes and can guide intervention development. PMID:26693932

Personal and Network Dynamics in Performance of Knowledge Workers: A Study of Australian Breast Radiologists.

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Seyedamir Tavakoli Taba

Full Text Available In this paper, we propose a theoretical model based upon previous studies about personal and social network dynamics of job performance. We provide empirical support for this model using real-world data within the context of the Australian radiology profession. An examination of radiologists' professional network topology through structural-positional and relational dimensions and radiologists' personal characteristics in terms of knowledge, experience and self-esteem is provided. Thirty one breast imaging radiologists completed a purpose designed questionnaire regarding their network characteristics and personal attributes. These radiologists also independently read a test set of 60 mammographic cases: 20 cases with cancer and 40 normal cases. A Jackknife free response operating characteristic (JAFROC method was used to measure the performance of the radiologists' in detecting breast cancers.Correlational analyses showed that reader performance was positively correlated with the social network variables of degree centrality and effective size, but negatively correlated with constraint and hierarchy. For personal characteristics, the number of mammograms read per year and self-esteem (self-evaluation positively correlated with reader performance. Hierarchical multiple regression analysis indicated that the combination of number of mammograms read per year and network's effective size, hierarchy and tie strength was the best fitting model, explaining 63.4% of the variance in reader performance. The results from this study indicate the positive relationship between reading high volumes of cases by radiologists and expertise development, but also strongly emphasise the association between effective social/professional interactions and informal knowledge sharing with high performance.

Insights into significant pathways and gene interaction networks underlying breast cancer cell line MCF-7 treated with 17β-estradiol (E2).

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Huan, Jinliang; Wang, Lishan; Xing, Li; Qin, Xianju; Feng, Lingbin; Pan, Xiaofeng; Zhu, Ling

2014-01-01

Estrogens are known to regulate the proliferation of breast cancer cells and to alter their cytoarchitectural and phenotypic properties, but the gene networks and pathways by which estrogenic hormones regulate these events are only partially understood. We used global gene expression profiling by Affymetrix GeneChip microarray analysis, with KEGG pathway enrichment, PPI network construction, module analysis and text mining methods to identify patterns and time courses of genes that are either stimulated or inhibited by estradiol (E2) in estrogen receptor (ER)-positive MCF-7 human breast cancer cells. Of the genes queried on the Affymetrix Human Genome U133 plus 2.0 microarray, we identified 628 (12h), 852 (24h) and 880 (48 h) differentially expressed genes (DEGs) that showed a robust pattern of regulation by E2. From pathway enrichment analysis, we found out the changes of metabolic pathways of E2 treated samples at each time point. At 12h time point, the changes of metabolic pathways were mainly focused on pathways in cancer, focal adhesion, and chemokine signaling pathway. At 24h time point, the changes were mainly enriched in neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction and calcium signaling pathway. At 48 h time point, the significant pathways were pathways in cancer, regulation of actin cytoskeleton, cell adhesion molecules (CAMs), axon guidance and ErbB signaling pathway. Of interest, our PPI network analysis and module analysis found that E2 treatment induced enhancement of PRSS23 at the three time points and PRSS23 was in the central position of each module. Text mining results showed that the important genes of DEGs have relationship with signal pathways, such as ERbB pathway (AREG), Wnt pathway (NDP), MAPK pathway (NTRK3, TH), IP3 pathway (TRA@) and some transcript factors (TCF4, MAF). Our studies highlight the diverse gene networks and metabolic and cell regulatory pathways through which E2 operates to achieve its

Artificial neural network analysis to assess hypernasality in patients treated for oral or oropharyngeal cancer

NARCIS (Netherlands)

de Bruijn, Marieke; ten Bosch, Louis; Kuik, Dirk J.; Langendijk, Johannes A.; Leemans, C. Rene; Verdonck-de Leeuw, Irma

2011-01-01

Objective. Investigation of applicability of neural network feature analysis of nasalance in speech to assess hypernasality in speech of patients treated for oral or oropharyngeal cancer. Patients and methods. Speech recordings of 51 patients and of 18 control speakers were evaluated regarding

Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

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Jaroslaw Suchanski

Full Text Available In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first

Podoplanin increases the migration of human fibroblasts and affects the endothelial cell network formation: A possible role for cancer-associated fibroblasts in breast cancer progression.

Science.gov (United States)

Suchanski, Jaroslaw; Tejchman, Anna; Zacharski, Maciej; Piotrowska, Aleksandra; Grzegrzolka, Jedrzej; Chodaczek, Grzegorz; Nowinska, Katarzyna; Rys, Janusz; Dziegiel, Piotr; Kieda, Claudine; Ugorski, Maciej

2017-01-01

In our previous studies we showed that in breast cancer podoplanin-positive cancer-associated fibroblasts correlated positively with tumor size, grade of malignancy, lymph node metastasis, lymphovascular invasion and poor patients' outcome. Therefore, the present study was undertaken to assess if podoplanin expressed by fibroblasts can affect malignancy-associated properties of breast cancer cells. Human fibroblastic cell lines (MSU1.1 and Hs 578Bst) overexpressing podoplanin and control fibroblasts were co-cultured with breast cancer MDA-MB-231 and MCF7 cells and the impact of podoplanin expressed by fibroblasts on migration and invasiveness of breast cancer cells were studied in vitro. Migratory and invasive properties of breast cancer cells were not affected by the presence of podoplanin on the surface of fibroblasts. However, ectopic expression of podoplanin highly increases the migration of MSU1.1 and Hs 578Bst fibroblasts. The present study also revealed for the first time, that podoplanin expression affects the formation of pseudo tubes by endothelial cells. When human HSkMEC cells were co-cultured with podoplanin-rich fibroblasts the endothelial cell capillary-like network was characterized by significantly lower numbers of nodes and meshes than in co-cultures of endothelial cells with podoplanin-negative fibroblasts. The question remains as to how our experimental data can be correlated with previous clinical data showing an association between the presence of podoplanin-positive cancer-associated fibroblasts and progression of breast cancer. Therefore, we propose that expression of podoplanin by fibroblasts facilitates their movement into the tumor stroma, which creates a favorable microenvironment for tumor progression by increasing the number of cancer-associated fibroblasts, which produce numerous factors affecting proliferation, survival and invasion of cancer cells. In accordance with this, the present study revealed for the first time, that such

Dynamic transcription factor networks in epithelial-mesenchymal transition in breast cancer models.

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Siletz, Anaar; Schnabel, Michael; Kniazeva, Ekaterina; Schumacher, Andrew J; Shin, Seungjin; Jeruss, Jacqueline S; Shea, Lonnie D

2013-01-01

The epithelial-mesenchymal transition (EMT) is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs) are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy.

Dynamic transcription factor networks in epithelial-mesenchymal transition in breast cancer models.

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Anaar Siletz

Full Text Available The epithelial-mesenchymal transition (EMT is a complex change in cell differentiation that allows breast carcinoma cells to acquire invasive properties. EMT involves a cascade of regulatory changes that destabilize the epithelial phenotype and allow mesenchymal features to manifest. As transcription factors (TFs are upstream effectors of the genome-wide expression changes that result in phenotypic change, understanding the sequential changes in TF activity during EMT provides rich information on the mechanism of this process. Because molecular interactions will vary as cells progress from an epithelial to a mesenchymal differentiation program, dynamic networks are needed to capture the changing context of molecular processes. In this study we applied an emerging high-throughput, dynamic TF activity array to define TF activity network changes in three cell-based models of EMT in breast cancer based on HMLE Twist ER and MCF-7 mammary epithelial cells. The TF array distinguished conserved from model-specific TF activity changes in the three models. Time-dependent data was used to identify pairs of TF activities with significant positive or negative correlation, indicative of interdependent TF activity throughout the six-day study period. Dynamic TF activity patterns were clustered into groups of TFs that change along a time course of gene expression changes and acquisition of invasive capacity. Time-dependent TF activity data was combined with prior knowledge of TF interactions to construct dynamic models of TF activity networks as epithelial cells acquire invasive characteristics. These analyses show EMT from a unique and targetable vantage and may ultimately contribute to diagnosis and therapy.

Pathway and network analysis of cancer genomes

DEFF Research Database (Denmark)

Creixell, Pau; Reimand, Jueri; Haider, Syed

2015-01-01

Genomic information on tumors from 50 cancer types cataloged by the International Cancer Genome Consortium (ICGC) shows that only a few well-studied driver genes are frequently mutated, in contrast to many infrequently mutated genes that may also contribute to tumor biology. Hence there has been...

Topic Modeling of Smoking- and Cessation-Related Posts to the American Cancer Society's Cancer Survivor Network (CSN): Implications for Cessation Treatment for Cancer Survivors Who Smoke.

Science.gov (United States)

Westmaas, J Lee; McDonald, Bennett R; Portier, Kenneth M

2017-08-01

Smoking is a risk factor in at least 18 cancers, and approximately two-thirds of cancer survivors continue smoking following diagnosis. Text mining of survivors' online posts related to smoking and quitting could inform strategies to reduce smoking in this vulnerable population. We identified posts containing smoking/cessation-related keywords from the Cancer Survivors Network (CSN), an online cancer survivor community of 166 000 members and over 468 000 posts since inception. Unsupervised topic model analysis of posts since 2000 using Latent Dirichlet Allocation extracted 70 latent topics which two subject experts inspected for themes based on representative terms. Posterior analysis assessed the distribution of topics within posts, and the range of themes discussed across posts. Less than 1% of posts (n = 3998) contained smoking/cessation-related terms, and covered topics related to cancer diagnoses, treatments, and coping. The most frequent smoking-related topics were quit smoking methods (5.4% of posts), and the environment for quitters (2.9% of posts), such as the stigma associated with being a smoker diagnosed with cancer and lack of empathy experienced compared to nonsmokers. Smoking as a risk factor for one's diagnosis was a primary topic in only 1.7% of smoking/cessation-related posts. The low frequency of smoking/cessation-related posts may be due to expected criticism/stigma for smoking but may also suggests a need for health care providers to address smoking and assist with quitting in the diagnostic and treatment process. Topic model analysis revealed potential barriers that should be addressed in devising clinical or population-level interventions for cancer survivors who smoke. Although smoking is a major risk factor for cancer, little is known about cancer patients' or survivors' views or concerns about smoking and quitting. This study used text mining of posts to an online community of cancer patients and survivors to investigate contexts in which

Usage of Probabilistic and General Regression Neural Network for Early Detection and Prevention of Oral Cancer

OpenAIRE

Sharma, Neha; Om, Hari

2015-01-01

In India, the oral cancers are usually presented in advanced stage of malignancy. It is critical to ascertain the diagnosis in order to initiate most advantageous treatment of the suspicious lesions. The main hurdle in appropriate treatment and control of oral cancer is identification and risk assessment of early disease in the community in a cost-effective fashion. The objective of this research is to design a data mining model using probabilistic neural network and general regression neural...

Validation of Malayalam Version of National Comprehensive Cancer Network Distress Thermometer and its Feasibility in Oncology Patients.

Science.gov (United States)

Biji, M S; Dessai, Sampada; Sindhu, N; Aravind, Sithara; Satheesan, B

2018-01-01

This study was designed to translate and validate the National Comprehensive Cancer Network (NCCN) distress thermometer (DT) in regional language " Malayalam" and to see the feasibility of using it in our patients. (1) To translate and validate the NCCN DT. (2) To study the feasibility of using validated Malayalam translated DT in Malabar Cancer center. This is a single-arm prospective observational study. The study was conducted at author's institution between December 8, 2015, and January 20, 2016 in the Department of Cancer Palliative Medicine. This was a prospective observational study carried out in two phases. In Phase 1, the linguistic validation of the NCCN DT was done. In Phase 2, the feasibility, face validity, and utility of the translated of NCCN DT in accordance with QQ-10 too was done. SPSS version 16 (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc.) was used for analysis. Ten patients were enrolled in Phase 2. The median age was 51.5 years and 40% of patients were male. All patients had completed at least basic education up to the primary level. The primary site of cancer was heterogeneous. The NCCN DT completion rate was 100%. The face validity, utility, reliability, and feasibility were 100%, 100%, 100%, and 90%, respectively. It can be concluded that the Malayalam validated DT has high face validity, utility, and it is feasible for its use.

Uncovering robust patterns of microRNA co-expression across cancers using Bayesian Relevance Networks.

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Parameswaran Ramachandran

Full Text Available Co-expression networks have long been used as a tool for investigating the molecular circuitry governing biological systems. However, most algorithms for constructing co-expression networks were developed in the microarray era, before high-throughput sequencing-with its unique statistical properties-became the norm for expression measurement. Here we develop Bayesian Relevance Networks, an algorithm that uses Bayesian reasoning about expression levels to account for the differing levels of uncertainty in expression measurements between highly- and lowly-expressed entities, and between samples with different sequencing depths. It combines data from groups of samples (e.g., replicates to estimate group expression levels and confidence ranges. It then computes uncertainty-moderated estimates of cross-group correlations between entities, and uses permutation testing to assess their statistical significance. Using large scale miRNA data from The Cancer Genome Atlas, we show that our Bayesian update of the classical Relevance Networks algorithm provides improved reproducibility in co-expression estimates and lower false discovery rates in the resulting co-expression networks. Software is available at www.perkinslab.ca.

Convolutional neural networks for prostate cancer recurrence prediction

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Kumar, Neeraj; Verma, Ruchika; Arora, Ashish; Kumar, Abhay; Gupta, Sanchit; Sethi, Amit; Gann, Peter H.

2017-03-01

Accurate prediction of the treatment outcome is important for cancer treatment planning. We present an approach to predict prostate cancer (PCa) recurrence after radical prostatectomy using tissue images. We used a cohort whose case vs. control (recurrent vs. non-recurrent) status had been determined using post-treatment follow up. Further, to aid the development of novel biomarkers of PCa recurrence, cases and controls were paired based on matching of other predictive clinical variables such as Gleason grade, stage, age, and race. For this cohort, tissue resection microarray with up to four cores per patient was available. The proposed approach is based on deep learning, and its novelty lies in the use of two separate convolutional neural networks (CNNs) - one to detect individual nuclei even in the crowded areas, and the other to classify them. To detect nuclear centers in an image, the first CNN predicts distance transform of the underlying (but unknown) multi-nuclear map from the input HE image. The second CNN classifies the patches centered at nuclear centers into those belonging to cases or controls. Voting across patches extracted from image(s) of a patient yields the probability of recurrence for the patient. The proposed approach gave 0.81 AUC for a sample of 30 recurrent cases and 30 non-recurrent controls, after being trained on an independent set of 80 case-controls pairs. If validated further, such an approach might help in choosing between a combination of treatment options such as active surveillance, radical prostatectomy, radiation, and hormone therapy. It can also generalize to the prediction of treatment outcomes in other cancers.

A Systems’ Biology Approach to Study MicroRNA-Mediated Gene Regulatory Networks

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Xin Lai

2013-01-01

Full Text Available MicroRNAs (miRNAs are potent effectors in gene regulatory networks where aberrant miRNA expression can contribute to human diseases such as cancer. For a better understanding of the regulatory role of miRNAs in coordinating gene expression, we here present a systems biology approach combining data-driven modeling and model-driven experiments. Such an approach is characterized by an iterative process, including biological data acquisition and integration, network construction, mathematical modeling and experimental validation. To demonstrate the application of this approach, we adopt it to investigate mechanisms of collective repression on p21 by multiple miRNAs. We first construct a p21 regulatory network based on data from the literature and further expand it using algorithms that predict molecular interactions. Based on the network structure, a detailed mechanistic model is established and its parameter values are determined using data. Finally, the calibrated model is used to study the effect of different miRNA expression profiles and cooperative target regulation on p21 expression levels in different biological contexts.

Population-based cancer screening programmes in low-income and middle-income countries: regional consultation of the International Cancer Screening Network in India.

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Sivaram, Sudha; Majumdar, Gautam; Perin, Douglas; Nessa, Ashrafun; Broeders, Mireille; Lynge, Elsebeth; Saraiya, Mona; Segnan, Nereo; Sankaranarayanan, Rengaswamy; Rajaraman, Preetha; Trimble, Edward; Taplin, Stephen; Rath, G K; Mehrotra, Ravi

2018-02-01

The reductions in cancer morbidity and mortality afforded by population-based cancer screening programmes have led many low-income and middle-income countries to consider the implementation of national screening programmes in the public sector. Screening at the population level, when planned and organised, can greatly benefit the population, whilst disorganised screening can increase costs and reduce benefits. The International Cancer Screening Network (ICSN) was created to share lessons, experience, and evidence regarding cancer screening in countries with organised screening programmes. Organised screening programmes provide screening to an identifiable target population and use multidisciplinary delivery teams, coordinated clinical oversight committees, and regular review by a multidisciplinary evaluation board to maximise benefit to the target population. In this Series paper, we report outcomes of the first regional consultation of the ICSN held in Agartala, India (Sept 5-7, 2016), which included discussions from cancer screening programmes from Denmark, the Netherlands, USA, and Bangladesh. We outline six essential elements of population-based cancer screening programmes, and share recommendations from the meeting that policy makers might want to consider before implementation. Copyright © 2018 Elsevier Ltd. All rights reserved.

SNRFCB: sub-network based random forest classifier for predicting chemotherapy benefit on survival for cancer treatment.

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Shi, Mingguang; He, Jianmin

2016-04-01

Adjuvant chemotherapy (CTX) should be individualized to provide potential survival benefit and avoid potential harm to cancer patients. Our goal was to establish a computational approach for making personalized estimates of the survival benefit from adjuvant CTX. We developed Sub-Network based Random Forest classifier for predicting Chemotherapy Benefit (SNRFCB) based gene expression datasets of lung cancer. The SNRFCB approach was then validated in independent test cohorts for identifying chemotherapy responder cohorts and chemotherapy non-responder cohorts. SNRFCB involved the pre-selection of gene sub-network signatures based on the mutations and on protein-protein interaction data as well as the application of the random forest algorithm to gene expression datasets. Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer patients in the chemotherapy responder group (P = 0.008), but it was not beneficial to patients in the chemotherapy non-responder group (P = 0.657). Adjuvant CTX was significantly associated with the prolonged overall survival of lung cancer squamous cell carcinoma (SQCC) subtype patients in the chemotherapy responder cohorts (P = 0.024), but it was not beneficial to patients in the chemotherapy non-responder cohorts (P = 0.383). SNRFCB improved prediction performance as compared to the machine learning method, support vector machine (SVM). To test the general applicability of the predictive model, we further applied the SNRFCB approach to human breast cancer datasets and also observed superior performance. SNRFCB could provide recurrent probability for individual patients and identify which patients may benefit from adjuvant CTX in clinical trials.

The updated network meta-analysis of neoadjuvant therapy for HER2-positive breast cancer.

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Nakashoji, Ayako; Hayashida, Tetsu; Yokoe, Takamichi; Maeda, Hinako; Toyota, Tomoka; Kikuchi, Masayuki; Watanuki, Rurina; Nagayama, Aiko; Seki, Tomoko; Takahashi, Maiko; Abe, Takayuki; Kitagawa, Yuko

2018-01-01

We previously described a systematic assessment of the neoadjuvant therapies for human epidermal growth factor receptor-2 (HER2) positive breast cancer, using network meta-analysis. Accumulation of new clinical data has compelled us to update the analysis. Randomized trials comparing different anti-HER2 regimens in the neoadjuvant setting were included, and odds ratio for pathologic complete response (pCR) in seven treatment arms were assessed by pooling effect sizes. Direct and indirect comparisons using a Bayesian statistical model were performed. All statistical tests were two-sided. A database search identified 993 articles with 13 studies meeting the eligibility criteria, including three new studies with lapatinib (lpnb). In an indirect comparison, dual anti-HER2 agents with CT achieved a better pCR rate than other arms. The credibility intervals of CT + tzmb + lpnb arm were largely reduced compared to our former report, which we added sufficient clinical evidence by this update. Values of surface under the cumulative ranking (SUCRA) suggested that CT + tzmb + pzmb had the highest probability of being the best treatment arm for pCR, widening the difference between the top two dual-HER2 blockade arms compared to our former report. The overall consistency with our first report enhanced the credibility of the results. Network meta-analysis using new clinical data firmly establish that combining two anti-HER2 agents with CT is most effective against HER2-positive breast cancer in the neoadjuvant setting. New pzmb related trials are required to fully determine the best neoadjuvant dual-HER2 blockade regimen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesizing community wisdom: A model for sharing cancer-related resources through social networking and collaborative partnerships.

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Weiss, Jacob B; Lorenzi, Nancy M; Lorenzi, Nancy

2008-11-06

Despite the availability of community-based support services, cancer patients and survivors are not aware of many of these resources. Without access to community programs, cancer survivors are at risk for lower quality of care and lower quality of life. At the same time, non-profit community organizations lack access to advanced consumer informatics applications to effectively promote awareness of their services. In addition to the current models of print and online resource guides, new community-driven informatics approaches are needed to achieve the goal of comprehensive care for cancer survivors. We present the formulation of a novel model for synthesizing a local communitys collective wisdom of cancer-related resources through a combination of online social networking technologies and real-world collaborative partnerships. This approach can improve awareness of essential, but underutilized community resources.

Increased entropy of signal transduction in the cancer metastasis phenotype

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Teschendorff Andrew E

2010-07-01

Full Text Available Abstract Background The statistical study of biological networks has led to important novel biological insights, such as the presence of hubs and hierarchical modularity. There is also a growing interest in studying the statistical properties of networks in the context of cancer genomics. However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes. Results Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns. Using a breast cancer gene expression data set and a model network of protein interactions we derive constrained weighted networks defined by a stochastic information flux matrix reflecting expression correlations between interacting proteins. Based on this stochastic matrix we propose and compute an entropy measure that quantifies the degree of randomness in the local pattern of information flux around single genes. By comparing the local entropies in the non-metastatic versus metastatic breast cancer networks, we here show that breast cancers that metastasize are characterised by a small yet significant increase in the degree of randomness of local expression patterns. We validate this result in three additional breast cancer expression data sets and demonstrate that local entropy better characterises the metastatic phenotype than other non-entropy based measures. We show that increases in entropy can be used to identify genes and signalling pathways implicated in breast cancer metastasis and provide examples of de-novo discoveries of gene modules with known roles in apoptosis, immune-mediated tumour suppression, cell-cycle and tumour invasion. Importantly, we also identify a novel gene module within the insulin growth factor signalling pathway, alteration of which may

Influence networks based on coexpression improve drug target discovery for the development of novel cancer therapeutics

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2014-01-01

Background The demand for novel molecularly targeted drugs will continue to rise as we move forward toward the goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. Results We use this approach to prioritize genes as drug target candidates in a set of ER + breast tumor samples collected during the course of neoadjuvant treatment with the aromatase inhibitor letrozole. We show that influential genes, those with high influence scores, tend to be essential and include a higher proportion of essential genes than those prioritized based on their position (i.e. hubs or bottlenecks) within the same network. Additionally, we show that influential genes represent novel biologically relevant drug targets for the treatment of ER + breast cancers. Moreover, we demonstrate that gene influence differs between untreated tumors and residual tumors that have adapted to drug treatment. In this way, influence scores capture the context-dependent functions of genes and present the opportunity to design combination treatment strategies that take advantage of the tumor adaptation process. Conclusions Influence networks efficiently find essential genes as promising drug targets and combinations of targets to inform the development of molecularly targeted drugs and their use. PMID:24495353

Brain Functional Connectivity in Small Cell Lung Cancer Population after Chemotherapy Treatment: an ICA fMRI Study

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Bromis, K.; Kakkos, I.; Gkiatis, K.; Karanasiou, I. S.; Matsopoulos, G. K.

2017-11-01

Previous neurocognitive assessments in Small Cell Lung Cancer (SCLC) population, highlight the presence of neurocognitive impairments (mainly in attention processing and executive functioning) in this type of cancer. The majority of these studies, associate these deficits with the Prophylactic Cranial Irradiation (PCI) that patients undergo in order to avoid brain metastasis. However, there is not much evidence exploring cognitive impairments induced by chemotherapy in SCLC patients. For this reason, we aimed to investigate the underlying processes that may potentially affect cognition by examining brain functional connectivity in nineteen SCLC patients after chemotherapy treatment, while additionally including fourteen healthy participants as control group. Independent Component Analysis (ICA) is a functional connectivity measure aiming to unravel the temporal correlation between brain regions, which are called brain networks. We focused on two brain networks related to the aforementioned cognitive functions, the Default Mode Network (DMN) and the Task-Positive Network (TPN). Permutation tests were performed between the two groups to assess the differences and control for familywise errors in the statistical parametric maps. ICA analysis showed functional connectivity disruptions within both of the investigated networks. These results, propose a detrimental effect of chemotherapy on brain functioning in the SCLC population.

Validation of malayalam version of national comprehensive cancer network distress thermometer and its feasibility in oncology patients

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M S Biji

2018-01-01

Full Text Available Context: This study was designed to translate and validate the National Comprehensive Cancer Network (NCCN distress thermometer (DT in regional language " Malayalam" and to see the feasibility of using it in our patients. Aims: (1 To translate and validate the NCCN DT. (2 To study the feasibility of using validated Malayalam translated DT in Malabar Cancer center. Settings and Design: This is a single-arm prospective observational study. The study was conducted at author's institution between December 8, 2015, and January 20, 2016 in the Department of Cancer Palliative Medicine. Materials and Methods: This was a prospective observational study carried out in two phases. In Phase 1, the linguistic validation of the NCCN DT was done. In Phase 2, the feasibility, face validity, and utility of the translated of NCCN DT in accordance with QQ-10 too was done. Statistical Analysis Used: SPSS version 16 (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc. was used for analysis. Results: Ten patients were enrolled in Phase 2. The median age was 51.5 years and 40% of patients were male. All patients had completed at least basic education up to the primary level. The primary site of cancer was heterogeneous. The NCCN DT completion rate was 100%. The face validity, utility, reliability, and feasibility were 100%, 100%, 100%, and 90%, respectively. Conclusion: It can be concluded that the Malayalam validated DT has high face validity, utility, and it is feasible for its use.

Detection of breast cancer using advanced techniques of data mining with neural networks

International Nuclear Information System (INIS)

Ortiz M, J. A.; Celaya P, J. M.; Martinez B, M. R.; Solis S, L. O.; Castaneda M, R.; Garza V, I.; Martinez F, M.; Lopez H, Y.; Ortiz R, J. M.

2016-10-01

The breast cancer is one of the biggest health problems worldwide, is the most diagnosed cancer in women and prevention seems impossible since its cause is unknown, due to this; the early detection has a key role in the patient prognosis. In developing countries such as Mexico, where access to specialized health services is minimal, the regular clinical review is infrequent and there are not enough radiologists; the most common form of detection of breast cancer is through self-exploration, but this is only detected in later stages, when is already palpable. For these reasons, the objective of the present work is the creation of a system of computer assisted diagnosis (CAD x) using information analysis techniques such as data mining and advanced techniques of artificial intelligence, seeking to offer a previous medical diagnosis or a second opinion, as if it was a second radiologist in order to reduce the rate of mortality from breast cancer. In this paper, advances in the design of computational algorithms using computer vision techniques for the extraction of features derived from mammograms are presented. Using data mining techniques of data mining is possible to identify patients with a high risk of breast cancer. With the information obtained from the mammography analysis, the objective in the next stage will be to establish a methodology for the generation of imaging bio-markers to establish a breast cancer risk index for Mexican patients. In this first stage we present results of the classification of patients with high and low risk of suffering from breast cancer using neural networks. (Author)

A prospective audit of early stoma complications in colorectal cancer treatment throughout the Greater Manchester and Cheshire colorectal cancer network.

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Parmar, K L; Zammit, M; Smith, A; Kenyon, D; Lees, N P

2011-08-01

The study aimed to identify the incidence of early stoma problems after surgery for colorectal cancer to identify predisposing factors and to assess the effect on discharge from hospital and the greater need for community stoma care. A prospective study of 192 patients was carried out over a six-month period in the 13 units of the Greater Manchester and Cheshire Cancer Network. Stoma problems were categorized into fistula, leakage, pancaking, necrosis, retraction, separation, stenosis, skin problems, parastomal hernia, suboptimal stoma site and need for resiting or refashioning. Differences in incidence between units (anonymized) were analysed, and the effect of stoma complications on length of hospital stay and the need for additional community stoma care was determined. One hundred and ninety-two patients with stomas were included, of which 52 (27.1%) were identified as being problematic (range 0-66.7% between units). Significant risk factors included stoma type (colostomy) (P stoma length (P = 0.006), higher BMI (P = 0.043), emergency surgery (P = 0.002) and lack of preoperative site marking (P stomas were associated with longer hospital stay (P care (P Stoma type, stoma length, body mass index, emergency surgery and lack of preoperative marking were significant risk factors. Overall complication rates compare favourably with other studies. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer.

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Du, Zhou; Sun, Tong; Hacisuleyman, Ezgi; Fei, Teng; Wang, Xiaodong; Brown, Myles; Rinn, John L; Lee, Mary Gwo-Shu; Chen, Yiwen; Kantoff, Philip W; Liu, X Shirley

2016-03-15

Mounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. However, the prevalence, functional significance and targets of lncRNA-mediated sponge regulation of cancer are mostly unknown. Here we identify a lncRNA-mediated sponge regulatory network that affects the expression of many protein-coding prostate cancer driver genes, by integrating analysis of sequence features and gene expression profiles of both lncRNAs and protein-coding genes in tumours. We confirm the tumour-suppressive function of two lncRNAs (TUG1 and CTB-89H12.4) and their regulation of PTEN expression in prostate cancer. Surprisingly, one of the two lncRNAs, TUG1, was previously known for its function in polycomb repressive complex 2 (PRC2)-mediated transcriptional regulation, suggesting its sub-cellular localization-dependent function. Our findings not only suggest an important role of lncRNA-mediated sponge regulation in cancer, but also underscore the critical influence of cytoplasmic localization on the efficacy of a sponge lncRNA.

Breast Cancer Chemoprevention: A Network Meta-Analysis of Randomized Controlled Trials.

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Mocellin, Simone; Pilati, Pierluigi; Briarava, Marta; Nitti, Donato

2016-02-01

Several agents have been advocated for breast cancer primary prevention. However, few of them appear effective, the associated severe adverse effects limiting their uptake. We performed a comprehensive search for randomized controlled trials (RCTs) reporting on the ability of chemoprevention agents (CPAs) to reduce the incidence of primary breast carcinoma. Using network meta-analysis, we ranked CPAs based simultaneously on efficacy and acceptability (an inverse measure of toxicity). All statistical tests were two-sided. We found 48 eligible RCTs, enrolling 271 161 women randomly assigned to receive either placebo or one of 21 CPAs. Aromatase inhibitors (anastrozole and exemestane, considered a single CPA class because of the lack of between-study heterogeneity; relative risk [RR] = 0.468, 95% confidence interval [CI] = 0.346 to 0.634), arzoxifene (RR = 0.415, 95% CI = 0.253 to 0.682), lasofoxifene (RR = 0.208, 95% CI = 0.079 to 0.544), raloxifene (RR = 0.572, 95% CI = 0.372 to 0.881), tamoxifen (RR = 0.708, 95% CI = 0.595 to 0.842), and tibolone (RR = 0.317, 95% CI = 0.127 to 0.792) were statistically significantly associated with a therapeutic effect, which was restricted to estrogen receptor-positive tumors of postmenopausal women (except for tamoxifen, which is active also during premenopause). Network meta-analysis ranking showed that the new selective estrogen receptor modulators (SERMs) arzoxifene, lasofoxifene, and raloxifene have the best benefit-risk ratio. Aromatase inhibitors and tamoxifen ranked second and third, respectively. These results provide physicians and health care regulatory agencies with RCT-based evidence on efficacy and acceptability of currently available breast cancer CPAs; at the same time, we pinpoint how much work still remains to be done before pharmacological primary prevention becomes a routine option to reduce the burden of this disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For

A fully-automated neural network analysis of AFM force-distance curves for cancer tissue diagnosis

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Minelli, Eleonora; Ciasca, Gabriele; Sassun, Tanya Enny; Antonelli, Manila; Palmieri, Valentina; Papi, Massimiliano; Maulucci, Giuseppe; Santoro, Antonio; Giangaspero, Felice; Delfini, Roberto; Campi, Gaetano; De Spirito, Marco

2017-10-01

Atomic Force Microscopy (AFM) has the unique capability of probing the nanoscale mechanical properties of biological systems that affect and are affected by the occurrence of many pathologies, including cancer. This capability has triggered growing interest in the translational process of AFM from physics laboratories to clinical practice. A factor still hindering the current use of AFM in diagnostics is related to the complexity of AFM data analysis, which is time-consuming and needs highly specialized personnel with a strong physical and mathematical background. In this work, we demonstrate an operator-independent neural-network approach for the analysis of surgically removed brain cancer tissues. This approach allowed us to distinguish—in a fully automated fashion—cancer from healthy tissues with high accuracy, also highlighting the presence and the location of infiltrating tumor cells.

Probability of Alzheimer's disease in breast cancer survivors based on gray-matter structural network efficiency.

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Kesler, Shelli R; Rao, Vikram; Ray, William J; Rao, Arvind

2017-01-01

Breast cancer chemotherapy is associated with accelerated aging and potentially increased risk for Alzheimer's disease (AD). We calculated the probability of AD diagnosis from brain network and demographic and genetic data obtained from 47 female AD converters and 47 matched healthy controls. We then applied this algorithm to data from 78 breast cancer survivors. The classifier discriminated between AD and healthy controls with 86% accuracy ( P  < .0001). Chemotherapy-treated breast cancer survivors demonstrated significantly higher probability of AD compared to healthy controls ( P  < .0001) and chemotherapy-naïve survivors ( P  = .007), even after stratifying for apolipoprotein e4 genotype. Chemotherapy-naïve survivors also showed higher AD probability compared to healthy controls ( P  = .014). Chemotherapy-treated breast cancer survivors who have a particular profile of brain structure may have a higher risk for AD, especially those who are older and have lower cognitive reserve.

Enhancing deep convolutional neural network scheme for breast cancer diagnosis with unlabeled data.

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Sun, Wenqing; Tseng, Tzu-Liang Bill; Zhang, Jianying; Qian, Wei

2017-04-01

In this study we developed a graph based semi-supervised learning (SSL) scheme using deep convolutional neural network (CNN) for breast cancer diagnosis. CNN usually needs a large amount of labeled data for training and fine tuning the parameters, and our proposed scheme only requires a small portion of labeled data in training set. Four modules were included in the diagnosis system: data weighing, feature selection, dividing co-training data labeling, and CNN. 3158 region of interests (ROIs) with each containing a mass extracted from 1874 pairs of mammogram images were used for this study. Among them 100 ROIs were treated as labeled data while the rest were treated as unlabeled. The area under the curve (AUC) observed in our study was 0.8818, and the accuracy of CNN is 0.8243 using the mixed labeled and unlabeled data. Copyright © 2016. Published by Elsevier Ltd.

Formal modeling and analysis of ER-α associated Biological Regulatory Network in breast cancer

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Samra Khalid

2016-10-01

Full Text Available Background Breast cancer (BC is one of the leading cause of death among females worldwide. The increasing incidence of BC is due to various genetic and environmental changes which lead to the disruption of cellular signaling network(s. It is a complex disease in which several interlinking signaling cascades play a crucial role in establishing a complex regulatory network. The logical modeling approach of René Thomas has been applied to analyze the behavior of estrogen receptor-alpha (ER-α associated Biological Regulatory Network (BRN for a small part of complex events that leads to BC metastasis. Methods A discrete model was constructed using the kinetic logic formalism and its set of logical parameters were obtained using the model checking technique implemented in the SMBioNet software which is consistent with biological observations. The discrete model was further enriched with continuous dynamics by converting it into an equivalent Petri Net (PN to analyze the logical parameters of the involved entities. Results In-silico based discrete and continuous modeling of ER-α associated signaling network involved in BC provides information about behaviors and gene-gene interaction in detail. The dynamics of discrete model revealed, imperative behaviors represented as cyclic paths and trajectories leading to pathogenic states such as metastasis. Results suggest that the increased expressions of receptors ER-α, IGF-1R and EGFR slow down the activity of tumor suppressor genes (TSGs such as BRCA1, p53 and Mdm2 which can lead to metastasis. Therefore, IGF-1R and EGFR are considered as important inhibitory targets to control the metastasis in BC. Conclusion The in-silico approaches allow us to increase our understanding of the functional properties of living organisms. It opens new avenues of investigations of multiple inhibitory targets (ER-α, IGF-1R and EGFR for wet lab experiments as well as provided valuable insights in the treatment of cancers

Targeting Stromal-Cancer Cell Crosstalk Networks in Ovarian Cancer Treatment

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Tsz-Lun Yeung

2016-01-01

Full Text Available Ovarian cancer is a histologically, clinically, and molecularly diverse disease with a five-year survival rate of less than 30%. It has been estimated that approximately 21,980 new cases of epithelial ovarian cancer will be diagnosed and 14,270 deaths will occur in the United States in 2015, making it the most lethal gynecologic malignancy. Ovarian tumor tissue is composed of cancer cells and a collection of different stromal cells. There is increasing evidence that demonstrates that stromal involvement is important in ovarian cancer pathogenesis. Therefore, stroma-specific signaling pathways, stroma-derived factors, and genetic changes in the tumor stroma present unique opportunities for improving the diagnosis and treatment of ovarian cancer. Cancer-associated fibroblasts (CAFs are one of the major components of the tumor stroma that have demonstrated supportive roles in tumor progression. In this review, we highlight various types of signaling crosstalk between ovarian cancer cells and stromal cells, particularly with CAFs. In addition to evaluating the importance of signaling crosstalk in ovarian cancer progression, we discuss approaches that can be used to target tumor-promoting signaling crosstalk and how these approaches can be translated into potential ovarian cancer treatment.

Men's perspectives of prostate cancer screening: A systematic review of qualitative studies.

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Laura J James

Full Text Available Prostate cancer is the most commonly diagnosed non-skin cancer in men. Screening for prostate cancer is widely accepted; however concerns regarding the harms outweighing the benefits of screening exist. Although patient's play a pivotal role in the decision making process, men may not be aware of the controversies regarding prostate cancer screening. Therefore we aimed to describe men's attitudes, beliefs and experiences of prostate cancer screening.Systematic review and thematic synthesis of qualitative studies on men's perspectives of prostate cancer screening. Electronic databases and reference lists were searched to October 2016.Sixty studies involving 3,029 men aged from 18-89 years, who had been screened for prostate cancer by Prostate Specific Antigen (PSA or Digital Rectal Examination (DRE and not screened, across eight countries were included. Five themes were identified: Social prompting (trusting professional opinion, motivation from family and friends, proximity and prominence of cancer; gaining decisional confidence (overcoming fears, survival imperative, peace of mind, mental preparation, prioritising wellbeing; preserving masculinity (bodily invasion, losing sexuality, threatening manhood, medical avoidance; avoiding the unknown and uncertainties (taboo of cancer-related death, lacking tangible cause, physiological and symptomatic obscurity, ambiguity of the procedure, confusing controversies; and prohibitive costs.Men are willing to participate in prostate cancer screening to prevent cancer and gain reassurance about their health, particularly when supported or prompted by their social networks or healthcare providers. However, to do so they needed to mentally overcome fears of losing their masculinity and accept the intrusiveness of screening, the ambiguities about the necessity and the potential for substantial costs. Addressing the concerns and priorities of men may facilitate informed decisions about prostate cancer screening

Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer.

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Hung, Rayjean J; Ulrich, Cornelia M; Goode, Ellen L; Brhane, Yonathan; Muir, Kenneth; Chan, Andrew T; Marchand, Loic Le; Schildkraut, Joellen; Witte, John S; Eeles, Rosalind; Boffetta, Paolo; Spitz, Margaret R; Poirier, Julia G; Rider, David N; Fridley, Brooke L; Chen, Zhihua; Haiman, Christopher; Schumacher, Fredrick; Easton, Douglas F; Landi, Maria Teresa; Brennan, Paul; Houlston, Richard; Christiani, David C; Field, John K; Bickeböller, Heike; Risch, Angela; Kote-Jarai, Zsofia; Wiklund, Fredrik; Grönberg, Henrik; Chanock, Stephen; Berndt, Sonja I; Kraft, Peter; Lindström, Sara; Al Olama, Ali Amin; Song, Honglin; Phelan, Catherine; Wentzensen, Nicholas; Peters, Ulrike; Slattery, Martha L; Sellers, Thomas A; Casey, Graham; Gruber, Stephen B; Hunter, David J; Amos, Christopher I; Henderson, Brian

2015-11-01

Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted. We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided. We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10(-8), and it showed an association with lung cancer (P = 2.01 x 10(-6)), colorectal cancer (GECCO P = 6.72x10(-6); CORECT P = 3.32x10(-5)), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10(-6)), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003). Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e

Functional Module Analysis for Gene Coexpression Networks with Network Integration.

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Zhang, Shuqin; Zhao, Hongyu; Ng, Michael K

2015-01-01

Network has been a general tool for studying the complex interactions between different genes, proteins, and other small molecules. Module as a fundamental property of many biological networks has been widely studied and many computational methods have been proposed to identify the modules in an individual network. However, in many cases, a single network is insufficient for module analysis due to the noise in the data or the tuning of parameters when building the biological network. The availability of a large amount of biological networks makes network integration study possible. By integrating such networks, more informative modules for some specific disease can be derived from the networks constructed from different tissues, and consistent factors for different diseases can be inferred. In this paper, we have developed an effective method for module identification from multiple networks under different conditions. The problem is formulated as an optimization model, which combines the module identification in each individual network and alignment of the modules from different networks together. An approximation algorithm based on eigenvector computation is proposed. Our method outperforms the existing methods, especially when the underlying modules in multiple networks are different in simulation studies. We also applied our method to two groups of gene coexpression networks for humans, which include one for three different cancers, and one for three tissues from the morbidly obese patients. We identified 13 modules with three complete subgraphs, and 11 modules with two complete subgraphs, respectively. The modules were validated through Gene Ontology enrichment and KEGG pathway enrichment analysis. We also showed that the main functions of most modules for the corresponding disease have been addressed by other researchers, which may provide the theoretical basis for further studying the modules experimentally.

Median Filter Noise Reduction of Image and Backpropagation Neural Network Model for Cervical Cancer Classification

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Wutsqa, D. U.; Marwah, M.

2017-06-01

In this paper, we consider spatial operation median filter to reduce the noise in the cervical images yielded by colposcopy tool. The backpropagation neural network (BPNN) model is applied to the colposcopy images to classify cervical cancer. The classification process requires an image extraction by using a gray level co-occurrence matrix (GLCM) method to obtain image features that are used as inputs of BPNN model. The advantage of noise reduction is evaluated by comparing the performances of BPNN models with and without spatial operation median filter. The experimental result shows that the spatial operation median filter can improve the accuracy of the BPNN model for cervical cancer classification.

Stage at presentation of breast cancer in Luanda, Angola - a retrospective study.

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Lopes, Lygia Vieira; Miguel, Fernando; Freitas, Helga; Tavares, António; Pangui, Salvador; Castro, Clara; Lacerda, Gonçalo Forjaz; Longatto-Filho, Adhemar; Weiderpass, Elisabete; Santos, Lúcio Lara

2015-10-15

It is expected that, by 2020, 15 million new cases of cancer will occur every year in the world, one million of them in Africa. Knowledge of cancer trends in African countries is far from adequate, and improvements in cancer prevention efforts are urgently needed. The aim of this study was to characterize breast cancer clinically and pathologically at presentation in Luanda, Angola; we additionally provide quality information that will be useful for breast cancer care planning in the country. Data on breast cancer cases were retrieved from the Angolan Institute of Cancer Control, from 2006 to 2014. For women diagnosed in 2009 (5-years of follow-up), demographic, clinical and pathological information, at presentation, was collected, namely age at diagnosis, parity, methods used for pathological diagnoses, tumor pathological characteristics, stage of disease and treatment. Descriptive statistics were performed. The median age of women diagnosed with breast cancer in 2009 was 47 years old (range 25-89). The most frequent clinical presentation was breast swelling with axillary lymph nodes metastasis (44.9 %), followed by a mass larger than 5 cm (14.2 %) and lump (12.9 %). Invasive ductal carcinoma was the main histologic type (81.8 %). Only 10.1 % of cancer cases had a well differentiated histological grade. Cancers were diagnosed mostly at advanced stages (66.7 % in stage III and 11.1 % in stage IV). In this study, breast cancer was diagnosed at a very advanced stage. Although it reports data from a single cancer center in Luanda, Angola it reinforces the need for early diagnosis and increasing awareness. According to the main challenges related to breast cancer diagnosis and treatment herein presented, we propose a realistic framework that would allow for the implementation of a breast cancer care program, built under a strong network based on cooperation, teaching, audit, good practices and the organization of health services. Angola needs urgently a program for

The influence of health-specific social network site use on the psychological well-being of cancer-affected people.

Science.gov (United States)

Erfani, Seyedezahra Shadi; Blount, Yvette; Abedin, Babak

2016-05-01

We aimed to explore and examine how and in what ways the use of social network sites (SNSs) can improve health outcomes, specifically better psychological well-being, for cancer-affected people. Qualitative semi-structured interviews were conducted with users of the Ovarian Cancer Australia Facebook page (OCA Facebook), the exemplar SNS used in this study. Twenty-five women affected by ovarian cancer who were users of OCA Facebook were interviewed. A multi-theory perspective was employed to interpret the data. Most of the study participants used OCA Facebook daily. Some users were passive and only observed created content, while other users actively posted content and communicated with other members. Analysis showed that the use of this SNS enhanced social support for users, improved the users' experiences of social connectedness, and helped users learn and develop social presence, which ultimately improved their psychological well-being. The strong theoretical underpinning of our research and empirically derived results led to a new understanding of the capacity of SNSs to improve psychological well-being. Our study provides evidence showing how the integration of these tools into existing health services can enhance patients' psychological well-being. This study also contributes to the body of knowledge on the implications of SNS use for improving the psychological well-being of cancer-affected people. This research assessed the relationship between the use of SNSs, specifically OCA Facebook, and the psychological well-being of cancer-affected people. The study confirmed that using OCA Facebook can improve psychological well-being by demonstrating the potential value of SNSs as a support service in the healthcare industry. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Treatment results of 165 pediatric patients with non-metastatic nasopharyngeal carcinoma: A Rare Cancer Network study

International Nuclear Information System (INIS)

Ozyar, Enis; Selek, Ugur; Laskar, Siddihartha; Uzel, Omer; Anacak, Yavuz; Ben-Arush, Miriam; Polychronopoulou, Sopiha; Akman, Fadime; Wolden, Suzanne L.; Sarihan, Suereyya; Miller, Robert C.; Ozsahin, Mahmut; Abacioglu, Ufuk; Martin, Margarita; Caloglu, Murat; Scandolaro, Luciano; Szutowicz, Eva; Atahan, Ibtisam Lale

2006-01-01

Purpose: This Rare Cancer Network (RCN) study was performed in pediatric nasopharyngeal carcinoma (PNPC) patients to evaluate the optimal dose of radiotherapy and to determine prognostic factors. Patients and Methods: The study included 165 patients with the diagnosis of PNPC treated between 1978 and 2003. The median age was 14 years. There were 3 (1.8%) patients with stage I, 1 (0.6%) with IIA, 10 (6.1%) with IIB, 60 (36.4%) with III, 44 (26.7%) with IVA, and 47 (29%) with IVB disease. While 21 (12.7%) patients were treated with radiotherapy (RT) alone, 144 (87.3%) received chemotherapy and RT. The median follow-up time was 48 months. Results: The actuarial 5-year overall survival (OS) was 77.4% (95% CI: 70.06-84.72), whereas the actuarial 5-year disease-free survival (DFS) rate was 68.8% (95% CI: 61.33-76.31). In multivariate analysis, unfavorable factors were age >14 years for LRC (p = 0.04); male gender for DMFS (p = 0.03); T3/T4 disease for LRFS (p = 0.01); and N3 disease for DFS (p = 0.002) and OS (p = 0.002); EBRT dose of less than 66 Gy for LRFS (p = 0.02) and LRRFS (p = 0.0028); and patients treated with RT alone for LRFS (p = 0.0001), LRRFS (p = 0.007) and DFS (p = 0.02). Conclusion: Our results support the current practice of using combined radiation and chemotherapy for optimal treatment of NPC. However, research should be encouraged in an attempt to reduce the potential for long-term sequelae in pediatric patients given their relatively favorable prognosis and potential for longevity

Chemical kinetic mechanistic models to investigate cancer biology and impact cancer medicine

International Nuclear Information System (INIS)

Stites, Edward C

2013-01-01

Traditional experimental biology has provided a mechanistic understanding of cancer in which the malignancy develops through the acquisition of mutations that disrupt cellular processes. Several drugs developed to target such mutations have now demonstrated clinical value. These advances are unequivocal testaments to the value of traditional cellular and molecular biology. However, several features of cancer may limit the pace of progress that can be made with established experimental approaches alone. The mutated genes (and resultant mutant proteins) function within large biochemical networks. Biochemical networks typically have a large number of component molecules and are characterized by a large number of quantitative properties. Responses to a stimulus or perturbation are typically nonlinear and can display qualitative changes that depend upon the specific values of variable system properties. Features such as these can complicate the interpretation of experimental data and the formulation of logical hypotheses that drive further research. Mathematical models based upon the molecular reactions that define these networks combined with computational studies have the potential to deal with these obstacles and to enable currently available information to be more completely utilized. Many of the pressing problems in cancer biology and cancer medicine may benefit from a mathematical treatment. As work in this area advances, one can envision a future where such models may meaningfully contribute to the clinical management of cancer patients. (paper)

Providing supportive care to cancer patients: a study on inter-organizational relationships

Directory of Open Access Journals (Sweden)

Kevin Brazil

2008-02-01

Full Text Available Background: Supportive cancer care (SCC has historically been provided by organizations that work independently and possess limited inter-organizational coordination. Despite the recognition that SCC services must be better coordinated, little research has been done to examine inter-organizational relationships that would enable this goal. Objective: The purpose of this study was to describe relationships among programs that support those affected by cancer. Through this description the study objective was to identify the optimal approach to coordinating SCC in the community. Methods: Senior administrators in programs that provided care to persons and their families living with or affected by cancer participated in a personal interview. Setting: South-central Ontario, Canada. Study population: administrators from 43 (97% eligible programs consented to participate in the study. Results: Network analysis revealed a diffuse system where centralization was greater in operational than administrative activities. A greater number of provider cliques were present at the operational level than the administrative level. Respondents identified several priorities to improve the coordination of cancer care in the community including: improving standards of care; establishing a regional coordinating body; increasing resources; and improving communication between programs. Conclusion: Our results point to the importance of developing a better understanding on the types of relationships that exist among service programs if effective integrated models of care are to be developed.

Predictive time-series modeling using artificial neural networks for Linac beam symmetry: an empirical study.

Science.gov (United States)

Li, Qiongge; Chan, Maria F

2017-01-01

Over half of cancer patients receive radiotherapy (RT) as partial or full cancer treatment. Daily quality assurance (QA) of RT in cancer treatment closely monitors the performance of the medical linear accelerator (Linac) and is critical for continuous improvement of patient safety and quality of care. Cumulative longitudinal QA measurements are valuable for understanding the behavior of the Linac and allow physicists to identify trends in the output and take preventive actions. In this study, artificial neural networks (ANNs) and autoregressive moving average (ARMA) time-series prediction modeling techniques were both applied to 5-year daily Linac QA data. Verification tests and other evaluations were then performed for all models. Preliminary results showed that ANN time-series predictive modeling has more advantages over ARMA techniques for accurate and effective applicability in the dosimetry and QA field. © 2016 New York Academy of Sciences.

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations

NARCIS (Netherlands)

Fehringer, G. (Gordon); P. Kraft (Peter); P.D.P. Pharoah (Paul); R. Eeles (Rosalind); Chatterjee, N. (Nilanjan); F.R. Schumacher (Fredrick R); J.M. Schildkraut (Joellen); S. Lindstrom (Stephen); P. Brennan (Paul); H. Bickeböller (Heike); R. Houlston (Richard); M.T. Landi (Maria Teresa); N.E. Caporaso (Neil); Risch, A. (Angela); A.A. Al Olama (Ali Amin); S.I. Berndt (Sonja); Giovannucci, E.L. (Edward L.); H. Grönberg (Henrik); Z. Kote-Jarai; Ma, J. (Jing); K.R. Muir (K.); M.J. Stampfer (Meir J.); Stevens, V.L. (Victoria L.); F. Wiklund (Fredrik); W.C. Willett (Walter C.); E.L. Goode (Ellen); Permuth, J.B. (Jennifer B.); H. Risch (Harvey); Reid, B.M. (Brett M.); Bezieau, S. (Stephane); H. Brenner (Hermann); Chan, A.T. (Andrew T.); J. Chang-Claude (Jenny); T.J. Hudson (Thomas); Kocarnik, J.K. (Jonathan K.); P. Newcomb (Polly); Schoen, R.E. (Robert E.); Slattery, M.L. (Martha L.); White, E. (Emily); M.A. Adank (Muriel); H. Ahsan (Habibul); K. Aittomäki (Kristiina); Baglietto, L. (Laura); Blomquist, C. (Carl); F. Canzian (Federico); K. Czene (Kamila); I. dos Santos Silva (Isabel); Eliassen, A.H. (A. Heather); J.D. Figueroa (Jonine); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); M. García-Closas (Montserrat); M.M. Gaudet (Mia); Johnson, N. (Nichola); P. Hall (Per); A. Hazra (Aditi); R. Hein (Rebecca); Hofman, A. (Albert); J.L. Hopper (John); A. Irwanto (Astrid); M. Johansson (Mattias); R. Kaaks (Rudolf); M.G. Kibriya (Muhammad); P. Lichtner (Peter); J. Liu (Jianjun); E. Lund (Eiliv); Makalic, E. (Enes); A. Meindl (Alfons); B. Müller-Myhsok (B.); Muranen, T.A. (Taru A.); H. Nevanlinna (Heli); P.H.M. Peeters; J. Peto (Julian); R. Prentice (Ross); N. Rahman (Nazneen); M.-J. Sanchez (Maria-Jose); D.F. Schmidt (Daniel); R.K. Schmutzler (Rita); M.C. Southey (Melissa); Tamimi, R. (Rulla); S.P.L. Travis (Simon); C. Turnbull (Clare); Uitterlinden, A.G. (Andre G.); Z. Wang (Zhaoming); A.S. Whittemore (Alice); X.R. Yang (Xiaohong); W. Zheng (Wei); D. Buchanan (Daniel); G. Casey (Graham); G. Conti (Giario); C.K. Edlund (Christopher); S. Gallinger (Steve); R. Haile (Robert); M. Jenkins (Mark); Marchand, L. (Loïcle); Li, L. (Li); N.M. Lindor (Noralane); Schmit, S.L. (Stephanie L.); S.N. Thibodeau (Stephen); M.O. Woods (Michael); T. Rafnar (Thorunn); J. Gudmundsson (Julius); S.N. Stacey (Simon); Stefansson, K. (Kari); P. Sulem (Patrick); Chen, Y.A. (Y. Ann); J.P. Tyrer (Jonathan); Christiani, D.C. (David C.); Wei, Y. (Yongyue); H. Shen (Hongbing); Z. Hu (Zhibin); X.-O. Shu (Xiao-Ou); Shiraishi, K. (Kouya); A. Takahashi (Atsushi); Y. Bossé (Yohan); M. Obeidat (Ma'en); D.C. Nickle (David); W. Timens (Wim); M. Freedman (Matthew); Li, Q. (Qiyuan); D. Seminara (Daniela); S.J. Chanock (Stephen); Gong, J. (Jian); U. Peters (Ulrike); S.B. Gruber (Stephen); Amos, C.I. (Christopher I.); T.A. Sellers (Thomas A.); D.F. Easton (Douglas F.); D. Hunter (David); C.A. Haiman (Christopher A.); B.E. Henderson (Brian); R.J. Hung (Rayjean)

2016-01-01

textabstractIdentifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851

Propranolol and survival from breast cancer

DEFF Research Database (Denmark)

Cardwell, Chris R; Pottegård, Anton; Vaes, Evelien

2016-01-01

BACKGROUND: Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all......-cause mortality in eight European cohorts. METHODS: Incident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network. Propranolol and non-selective beta-blocker use was ascertained for each patient. Breast cancer-specific and all......-analysis techniques. Dose-response analyses by number of prescriptions were also performed. Analyses were repeated investigating propranolol use before cancer diagnosis. RESULTS: The combined study population included 55,252 and 133,251 breast cancer patients in the analysis of breast cancer-specific and all...

Program Spotlight: National Outreach Network's Community Health Educators

Science.gov (United States)

National Outreach Network of Community Health Educators located at Community Network Program Centers, Partnerships to Advance Cancer Health Equity, and NCI-designated cancer centers help patients and their families receive survivorship support.

Meta-analysis of cancer transcriptomes: A new approach to uncover molecular pathological events in different cancer tissues

Directory of Open Access Journals (Sweden)

Sundus Iqbal

2014-03-01

Full Text Available To explore secrets of metastatic cancers, individual expression of true sets of respective genes must spread across the tissue. In this study, meta-analysis for transcriptional profiles of oncogenes was carried out to hunt critical genes or networks helping in metastasizing cancers. For this, transcriptomic analysis of different cancerous tissues causing leukemia, lung, liver, spleen, colorectal, colon, breast, bladder, and kidney cancers was performed by extracting microarray expression data from online resource; Gene Expression Omnibus. A newly developed bioinformatics technique; Dynamic Impact Approach (DIA was applied for enrichment analysis of transcriptional profiles using Database for Annotation Visualization and Integrated Discovery (DAVID. Furthermore, oPOSSUM (v. 2.0 and Cytoscape (v. 2.8.2 were used for in-depth analysis of transcription factors and regulatory gene networks respectively. DAVID analysis uncovered the most significantly enriched pathways in molecular functions that were 'Ubiquitin thiolesterase activity' up regulated in blood, breast, bladder, colorectal, lung, spleen, prostrate cancer. 'Transforming growth factor beta receptor activity' was inhibited in all cancers except leukemia, colon and liver cancer. oPOSSUM further revealed highly over-represented Transcription Factors (TFs; Broad-complex_3, Broad-complex_4, and Foxd3 except for leukemia and bladder cancer. From these findings, it is possible to target genes and networks, play a crucial role in the development of cancer. In the future, these transcription factors can serve as potential candidates for the therapeutic drug targets which can impede the deadly spread.

Application of artificial intelligence using a convolutional neural network for detecting gastric cancer in endoscopic images.

Science.gov (United States)

Hirasawa, Toshiaki; Aoyama, Kazuharu; Tanimoto, Tetsuya; Ishihara, Soichiro; Shichijo, Satoki; Ozawa, Tsuyoshi; Ohnishi, Tatsuya; Fujishiro, Mitsuhiro; Matsuo, Keigo; Fujisaki, Junko; Tada, Tomohiro

2018-07-01

Image recognition using artificial intelligence with deep learning through convolutional neural networks (CNNs) has dramatically improved and been increasingly applied to medical fields for diagnostic imaging. We developed a CNN that can automatically detect gastric cancer in endoscopic images. A CNN-based diagnostic system was constructed based on Single Shot MultiBox Detector architecture and trained using 13,584 endoscopic images of gastric cancer. To evaluate the diagnostic accuracy, an independent test set of 2296 stomach images collected from 69 consecutive patients with 77 gastric cancer lesions was applied to the constructed CNN. The CNN required 47 s to analyze 2296 test images. The CNN correctly diagnosed 71 of 77 gastric cancer lesions with an overall sensitivity of 92.2%, and 161 non-cancerous lesions were detected as gastric cancer, resulting in a positive predictive value of 30.6%. Seventy of the 71 lesions (98.6%) with a diameter of 6 mm or more as well as all invasive cancers were correctly detected. All missed lesions were superficially depressed and differentiated-type intramucosal cancers that were difficult to distinguish from gastritis even for experienced endoscopists. Nearly half of the false-positive lesions were gastritis with changes in color tone or an irregular mucosal surface. The constructed CNN system for detecting gastric cancer could process numerous stored endoscopic images in a very short time with a clinically relevant diagnostic ability. It may be well applicable to daily clinical practice to reduce the burden of endoscopists.

Integrative analysis of lncRNAs and miRNAs with coding RNAs associated with ceRNA crosstalk network in triple negative breast cancer

Directory of Open Access Journals (Sweden)

Yuan NJ

2017-12-01

Full Text Available Naijun Yuan,1,* Guijuan Zhang,2,* Fengjie Bie,1 Min Ma,1 Yi Ma,3 Xuefeng Jiang,1 Yurong Wang,1,* Xiaoqian Hao1 1College of Traditional Chinese Medicine of Jinan University, Institute of Integrated Traditional Chinese and Western Medicine of Jinan University, 2The First Affiliated Hospital of Jinan University, 3Department of Cellular Biology, Guangdong Province Key Lab of Bioengineering Medicine, Institute of Biomedicine, Jinan University, Guangdong, China *These authors contributed equally to this work Abstract: Triple negative breast cancer (TNBC is a particular subtype of breast malignant tumor with poorer prognosis than other molecular subtypes. Currently, there is increasing focus on long non-coding RNAs (lncRNAs, which can act as competing endogenous RNAs (ceRNAs and suppress miRNA functions involved in post-transcriptional regulatory networks in the tumor. Therefore, to investigate specific mechanisms of TNBC carcinogenesis and improve treatment efficiency, we comprehensively integrated expression profiles, including data on mRNAs, lncRNAs and miRNAs obtained from 116 TNBC tissues and 11 normal tissues from The Cancer Genome Atlas. As a result, we selected the threshold with |log2FC|>2.0 and an adjusted p-value >0.05 to obtain the differentially expressed mRNAs, miRNAs and lncRNAs. Hereafter, weighted gene co-expression network analysis was performed to identify the expression characteristics of dysregulated genes. We obtained five co-expression modules and related clinical feature. By means of correlating gene modules with protein–protein interaction network analysis that had identified 22 hub mRNAs which could as hub target genes. Eleven key dysregulated differentially expressed micro RNAs (DEmiRNAs were identified that were significantly associated with the 22 hub potential target genes. Moreover, we found that 14 key differentially expressed lncRNAs could interact with the key DEmiRNAs. Then, the ceRNA crosstalk network of TNBC was

Evolutionary Origins of Cancer Driver Genes and Implications for Cancer Prognosis.

Science.gov (United States)

Chu, Xin-Yi; Jiang, Ling-Han; Zhou, Xiong-Hui; Cui, Ze-Jia; Zhang, Hong-Yu

2017-07-14

The cancer atavistic theory suggests that carcinogenesis is a reverse evolution process. It is thus of great interest to explore the evolutionary origins of cancer driver genes and the relevant mechanisms underlying the carcinogenesis. Moreover, the evolutionary features of cancer driver genes could be helpful in selecting cancer biomarkers from high-throughput data. In this study, through analyzing the cancer endogenous molecular networks, we revealed that the subnetwork originating from eukaryota could control the unlimited proliferation of cancer cells, and the subnetwork originating from eumetazoa could recapitulate the other hallmarks of cancer. In addition, investigations based on multiple datasets revealed that cancer driver genes were enriched in genes originating from eukaryota, opisthokonta, and eumetazoa. These results have important implications for enhancing the robustness of cancer prognosis models through selecting the gene signatures by the gene age information.

Reusability of coded data in the primary care electronic medical record: A dynamic cohort study concerning cancer diagnoses.

Science.gov (United States)

Sollie, Annet; Sijmons, Rolf H; Helsper, Charles; Numans, Mattijs E

2017-03-01

To assess quality and reusability of coded cancer diagnoses in routine primary care data. To identify factors that influence data quality and areas for improvement. A dynamic cohort study in a Dutch network database containing 250,000 anonymized electronic medical records (EMRs) from 52 general practices was performed. Coded data from 2000 to 2011 for the three most common cancer types (breast, colon and prostate cancer) was compared to the Netherlands Cancer Registry. Data quality is expressed in Standard Incidence Ratios (SIRs): the ratio between the number of coded cases observed in the primary care network database and the expected number of cases based on the Netherlands Cancer Registry. Ratios were multiplied by 100% for readability. The overall SIR was 91.5% (95%CI 88.5-94.5) and showed improvement over the years. SIRs differ between cancer types: from 71.5% for colon cancer in males to 103.9% for breast cancer. There are differences in data quality (SIRs 76.2% - 99.7%) depending on the EMR system used, with SIRs up to 232.9% for breast cancer. Frequently observed errors in routine healthcare data can be classified as: lack of integrity checks, inaccurate use and/or lack of codes, and lack of EMR system functionality. Re-users of coded routine primary care Electronic Medical Record data should be aware that 30% of cancer cases can be missed. Up to 130% of cancer cases found in the EMR data can be false-positive. The type of EMR system and the type of cancer influence the quality of coded diagnosis registry. While data quality can be improved (e.g. through improving system design and by training EMR system users), re-use should only be taken care of by appropriately trained experts. Copyright © 2016. Published by Elsevier B.V.

Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic Associations

NARCIS (Netherlands)

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fredrick R.; Schildkraut, Joellen M.; Lindstrom, Sara; Brennan, Paul; Bickeboller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Al Olama, Ali Amin; Berndt, Sonja I.; Giovannucci, Edward L.; Gronberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J.; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter C.; Goode, Ellen L.; Permuth, Jennifer B.; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomaki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; dos-Santos-Silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine D.; Timens, Wim

2016-01-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate, and colorectal cancer reveals novel pleiotropic associations

NARCIS (Netherlands)

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fredrick R.; Schildkraut, Joellen M.; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Al Olama, Ali Amin; Berndt, Sonja I.; Giovannucci, Edward L.; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir J.; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter C.; Goode, Ellen L.; Permuth, Jennifer B.; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; Dos-Santos-silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine D.; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Wang, Zhaoming; Whittemore, Alice S.; Yang, Xiaohong R.; Zheng, Wei; Buchanan, Daniel D.; Casey, Graham; Conti, David V.; Edlund, Christopher K.; Gallinger, Steven; Haile, Robert W.; Jenkins, Mark; Marchand, Loïcle; Li, Li; Lindor, Noralene M.; Schmit, Stephanie L.; Thibodeau, Stephen N.; Woods, Michael O.; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N.; Stefansson, Kari; Sulem, Patrick; Chen, Y. Ann; Tyrer, Jonathan P.; Christiani, David C.; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma'en; Nickle, David; Timens, Wim; Freedman, Matthew L.; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J.; Gong, Jian; Peters, Ulrike; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, Brian E.; Hung, Rayjean J.

2016-01-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-stage approach to conduct genome-wide association studies for lung, ovary, breast, prostate, and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820

Updating risk prediction tools: a case study in prostate cancer.

Science.gov (United States)

Ankerst, Donna P; Koniarski, Tim; Liang, Yuanyuan; Leach, Robin J; Feng, Ziding; Sanda, Martin G; Partin, Alan W; Chan, Daniel W; Kagan, Jacob; Sokoll, Lori; Wei, John T; Thompson, Ian M

2012-01-01

Online risk prediction tools for common cancers are now easily accessible and widely used by patients and doctors for informed decision-making concerning screening and diagnosis. A practical problem is as cancer research moves forward and new biomarkers and risk factors are discovered, there is a need to update the risk algorithms to include them. Typically, the new markers and risk factors cannot be retrospectively measured on the same study participants used to develop the original prediction tool, necessitating the merging of a separate study of different participants, which may be much smaller in sample size and of a different design. Validation of the updated tool on a third independent data set is warranted before the updated tool can go online. This article reports on the application of Bayes rule for updating risk prediction tools to include a set of biomarkers measured in an external study to the original study used to develop the risk prediction tool. The procedure is illustrated in the context of updating the online Prostate Cancer Prevention Trial Risk Calculator to incorporate the new markers %freePSA and [-2]proPSA measured on an external case-control study performed in Texas, U.S.. Recent state-of-the art methods in validation of risk prediction tools and evaluation of the improvement of updated to original tools are implemented using an external validation set provided by the U.S. Early Detection Research Network. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cervical cancer: a qualitative study on subjectivity, family, gender and health services

OpenAIRE

López-Cervantes Malaquías; Mohar-Betancourt Alejandro; Tirado-Gómez Laura L; Pelcastre-Villafuerte Blanca E

2007-01-01

Abstract Background In 2002, cervical cancer was one of the leading causes of death in Mexico. Quantitative techniques allowed for the identification of socioeconomic, behavioral and biological characteristics that are part of its etiology. However such characteristics, are inadequate to explain sufficiently the role that emotions, family networks and socially-constructed categories such as gender play in the demand and utilization of health services for cervical cancer diagnosis and treatmen...

CRCHD Integrated Networks

Science.gov (United States)

INB supports two network-based programs—the National Outreach Network (NON) and the Geographic Management of Cancer Health Disparities Program (GMaP)—as well as advising on women’s health and sexual and gender minority opportunities within and across the NCI.

[Clues to differentiate pregnancy-associated breast cancer from those diagnosed in postpartum period: A monocentric experience of pregnancy-associated cancer network (CALG)].

Science.gov (United States)

Boudy, Anne-Sophie; Naoura, Iptissem; Zilberman, Sonia; Gligorov, Joseph; Chabbert-Buffet, Nathalie; Ballester, Marcos; Selleret, Lise; Darai, Emile

2017-06-01

To compare epidemiological, histological, therapeutic characteristics and prognosis of patients with breast cancer diagnosed during pregnancy with those diagnosed in postpartum period at a national expert center, « Cancer Associé à La Grossesse » network. Retrospective study of 108 patients with a pregnancy-associated breast cancer (PABC) between 2002 and 2016 comparing 51 patients with PABC during pregnancy and 57 patients with PABC of postpartum. Median gestational age at diagnosis was 16 weeks of gestation (WG). Median size (P=0.92), initial axillary pathology (P=0.29), histological type (P=0.33) and hormone receptor positive (P=0.93), were similar between groups. PABC during pregnancy overexpressed less frequently HER2 (12 % vs 36 %, P=0.003) and were less proliferant (Ki67≥15 %; 64 % vs 75 %, P=0.018) with less radical surgery (45 % vs 70 %, P=0.008). Sentinel lymph node biopsy was performed in 8 patients during pregnancy. Less patients of PABC during pregnancy received trastuzumab 12 % vs 37 %, P=0.003. Median delivery term was 37 WG. Median follow-up 3.2 vs 5.6 years (P=0.002) and recurrence rate for PABC during pregnancy and of postpartum were 3.2 vs 5.6 years (P=0.002) and 12 % vs 32 % (P=0.01), respectively. Our results emphasize histological, surgical and adjuvant treatment differences imposing differentiating PABC during pregnancy from those diagnosed in the postpartum period. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

An integrated approach of network-based systems biology, molecular docking, and molecular dynamics approach to unravel the role of existing antiviral molecules against AIDS-associated cancer.

Science.gov (United States)

Omer, Ankur; Singh, Poonam

2017-05-01

A serious challenge in cancer treatment is to reposition the activity of various already known drug candidates against cancer. There is a need to rewrite and systematically analyze the detailed mechanistic aspect of cellular networks to gain insight into the novel role played by various molecules. Most Human Immunodeficiency Virus infection-associated cancers are caused by oncogenic viruses like Human Papilloma Viruses and Epstein-Bar Virus. As the onset of AIDS-associated cancers marks the severity of AIDS, there might be possible interconnections between the targets and mechanism of both the diseases. We have explored the possibility of certain antiviral compounds to act against major AIDS-associated cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, and Cervical Cancer with the help of systems pharmacology approach that includes screening for targets and molecules through the construction of a series of drug-target and drug-target-diseases network. Two molecules (Calanolide A and Chaetochromin B) and the target "HRAS" were finally screened with the help of molecular docking and molecular dynamics simulation. The results provide novel antiviral molecules against HRAS target to treat AIDS defining cancers and an insight for understanding the pharmacological, therapeutic aspects of similar unexplored molecules against various cancers.

Social network, autonomy, and adherence correlates of future time perspective in patients with head and neck cancer.

Science.gov (United States)

Baldensperger, Linda; Wiedemann, Amelie U; Wessel, Lauri; Keilholz, Ulrich; Knoll, Nina

2018-06-01

Socioemotional selectivity theory proposes that, with more limited future time perspective (FTP), the meaning of individual life goals shifts from instrumental and long-term goals, such as autonomy, to emotionally meaningful and short-term life goals, especially concerning meaningful social relationships. Adverse side effects of cancer therapy may conflict with the realization of emotionally meaningful goals leading to nonadherence. In line with the theoretical assumptions, this study aimed to investigate (a) associations among disease symptoms, physical and cognitive limitations, and FTP and (b) among FTP, family network size, striving for autonomy, and treatment adherence. One hundred fifty-seven patients (43-90 years; 75% male) with head and/or neck cancer of a German University Medical Centre completed a questionnaire measuring FTP, age, disease symptoms, physical and cognitive functioning, family network size, and treatment adherence. Autonomy was assessed with a card sort task. A structural equation model yielded an acceptable fit χ 2 (28) = 44.41, P = .025, χ 2 /df = 1.59, root mean square error of approximation = 0.06 (90% CI = 0.02, 0.09), Tucker-Lewis Index = 0.92, and Comparative Fit Index = 0.96. An increased level of disease symptoms and physical and cognitive limitations was related to a shorter subjective FTP. Furthermore, individuals with a limited FTP reported a smaller family network, a lowered quest for autonomy, and lower treatment adherence. Hypotheses derived from socioemotional selectivity theory were supported by the data. Longitudinal investigations should follow to corroborate findings and to focus on underlying mechanisms as improving patients FTP may play a crucial role in future disease management programs. Copyright © 2018 John Wiley & Sons, Ltd.

Parameter optimization for constructing competing endogenous RNA regulatory network in glioblastoma multiforme and other cancers.

Science.gov (United States)

Chiu, Yu-Chiao; Hsiao, Tzu-Hung; Chen, Yidong; Chuang, Eric Y

2015-01-01

In addition to direct targeting and repressing mRNAs, recent studies reported that microRNAs (miRNAs) can bridge up an alternative layer of post-transcriptional gene regulatory networks. The competing endogenous RNA (ceRNA) regulation depicts the scenario where pairs of genes (ceRNAs) sharing, fully or partially, common binding miRNAs (miRNA program) can establish coexpression through competition for a limited pool of the miRNA program. While the dynamics of ceRNA regulation among cellular conditions have been verified based on in silico and in vitro experiments, comprehensive investigation into the strength of ceRNA regulation in human datasets remains largely unexplored. Furthermore, pan-cancer analysis of ceRNA regulation, to our knowledge, has not been systematically investigated. In the present study we explored optimal conditions for ceRNA regulation, investigated functions governed by ceRNA regulation, and evaluated pan-cancer effects. We started by investigating how essential factors, such as the size of miRNA programs, the number of miRNA program binding sites, and expression levels of miRNA programs and ceRNAs affect the ceRNA regulation capacity in tumors derived from glioblastoma multiforme patients captured by The Cancer Genome Atlas (TCGA). We demonstrated that increased numbers of common targeting miRNAs as well as the abundance of binding sites enhance ceRNA regulation and strengthen coexpression of ceRNA pairs. Also, our investigation revealed that the strength of ceRNA regulation is dependent on expression levels of both miRNA programs and ceRNAs. Through functional annotation analysis, our results indicated that ceRNA regulation is highly associated with essential cellular functions and diseases including cancer. Furthermore, the highly intertwined ceRNA regulatory relationship enables constitutive and effective intra-function regulation of genes in diverse types of cancer. Using gene and microRNA expression datasets from TCGA, we successfully

Comparative Study of Intelligent Systems for Management of GIT Cancers

Directory of Open Access Journals (Sweden)

Labib Nevine

2017-01-01

Full Text Available Intelligent Systems contribute in the management of different GIT cancer types. The paper discusses different types of intelligent systems, classified according to the medical task achieved, such as early detection, diagnosis and prognosis. It is found out that these types include rule-based and case-based expert systems, artificial neural networks, genetic algorithms, machine learning, in addition to data mining techniques and statistical methods. The study focuses on comparing between different techniques and tools used. The comparison results in identifying the benefits of using data mining techniques for the diagnosis task, since it is based on huge amounts of data in order to discover new patterns hence new predisposing factors. It also points out the use of expert systems in the prognosis task, since this task is mainly based on the specialist experience that should be transferred to less- experienced medical professionals. Based on the previous results, it is recommended to develop an Intelligent Tutoring System (ITS that focuses on the early diagnosis of GIT cancers, since managing the disease depends mainly on proper diagnosis, and also to build an expert system that helps transferring GIT cancers management knowledge to medical doctors in different hospitals.

Reusability of coded data in the primary care electronic medical record : A dynamic cohort study concerning cancer diagnoses

NARCIS (Netherlands)

Sollie, Annet; Sijmons, Rolf H.; Helsper, Charles W.; Numans, Mattijs E.

Objectives: To assess quality and reusability of coded cancer diagnoses in routine primary care data. To identify factors that influence data quality and areas for improvement. Methods: A dynamic cohort study in a Dutch network database containing 250,000 anonymized electronic medical records (EMRs)

Proteome-wide dataset supporting functional study of tyrosine kinases in breast cancer

Directory of Open Access Journals (Sweden)

Nicos Angelopoulos

2016-06-01

Full Text Available Tyrosine kinases (TKs play an essential role in regulating various cellular activities and dysregulation of TK signaling contributes to oncogenesis. However, less than half of the TKs have been thoroughly studied. Through a combined use of RNAi and stable isotope labeling with amino acids in cell culture (SILAC-based quantitative proteomics, a global functional proteomic landscape of TKs in breast cancer was recently revealed highlighting a comprehensive and highly integrated signaling network regulated by TKs (Stebbing et al., 2015 [1]. We collate the enormous amount of the proteomic data in an open access platform, providing a valuable resource for studying the function of TKs in cancer and benefiting the science community. Here we present a detailed description related to this study (Stebbing et al., 2015 [1] and the raw data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the identifier http://www.ebi.ac.uk/pride/archive/projects/PXD002065.

Applying Social Network Analysis to Identify the Social Support Needs of Adolescent and Young Adult Cancer Patients and Survivors.

Science.gov (United States)

Koltai, Kolina; Walsh, Casey; Jones, Barbara; Berkelaar, Brenda L

2018-04-01

This article examines how theoretical and clinical applications of social network analysis (SNA) can inform opportunities for innovation and advancement of social support programming for adolescent and young adult (AYA) cancer patients and survivors. SNA can help address potential barriers and challenges to initiating and sustaining AYA peer support by helping to identify the diverse psychosocial needs among individuals in the AYA age range; find strategic ways to support and connect AYAs at different phases of the cancer trajectory with resources and services; and increase awareness of psychosocial resources and referrals from healthcare providers. Network perspectives on homophily, proximity, and evolution provide a foundational basis to explore the utility of SNA in AYA clinical care and research initiatives. The uniqueness of the AYA oncology community can also provide insight into extending and developing current SNA theories. Using SNA in AYA psychosocial cancer research has the potential to create new ideas and pathways for supporting AYAs across the continuum of care, while also extending theories of SNA. SNA may also prove to be a useful tool for examining social support resources for AYAs with various chronic health conditions and other like groups.

Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer

International Nuclear Information System (INIS)

Li, Ying; Zhao, Haixia; Wang, Yuzhong; Zheng, Hao; Yu, Wei; Chai, Hongyan; Zhang, Jing; Falck, John R.; Guo, Austin M.; Yue, Jiang; Peng, Renxiu; Yang, Jing

2013-01-01

human breast cancer. - Highlights: • Isoliquiritigenin induces growth inhibition and apoptosis in human breast cancer. • The proapoptotic action of isoliquiritigenin has been studied in vitro and in vivo. • Arachidonic acid metabolic network mediates isoliquiritigenin-induced apoptosis. • PI3K/Akt deactivation is asssociated with isoliquiritigenin-induced apoptosis. • Isoliquiritigenin may be a multi-target drug in the treatment of breast cancer

Integration of protein phosphorylation, acetylation, and methylation data sets to outline lung cancer signaling networks.

Science.gov (United States)

Grimes, Mark; Hall, Benjamin; Foltz, Lauren; Levy, Tyler; Rikova, Klarisa; Gaiser, Jeremiah; Cook, William; Smirnova, Ekaterina; Wheeler, Travis; Clark, Neil R; Lachmann, Alexander; Zhang, Bin; Hornbeck, Peter; Ma'ayan, Avi; Comb, Michael

2018-05-22

Protein posttranslational modifications (PTMs) have typically been studied independently, yet many proteins are modified by more than one PTM type, and cell signaling pathways somehow integrate this information. We coupled immunoprecipitation using PTM-specific antibodies with tandem mass tag (TMT) mass spectrometry to simultaneously examine phosphorylation, methylation, and acetylation in 45 lung cancer cell lines compared to normal lung tissue and to cell lines treated with anticancer drugs. This simultaneous, large-scale, integrative analysis of these PTMs using a cluster-filtered network (CFN) approach revealed that cell signaling pathways were outlined by clustering patterns in PTMs. We used the t-distributed stochastic neighbor embedding (t-SNE) method to identify PTM clusters and then integrated each with known protein-protein interactions (PPIs) to elucidate functional cell signaling pathways. The CFN identified known and previously unknown cell signaling pathways in lung cancer cells that were not present in normal lung epithelial tissue. In various proteins modified by more than one type of PTM, the incidence of those PTMs exhibited inverse relationships, suggesting that molecular exclusive "OR" gates determine a large number of signal transduction events. We also showed that the acetyltransferase EP300 appears to be a hub in the network of pathways involving different PTMs. In addition, the data shed light on the mechanism of action of geldanamycin, an HSP90 inhibitor. Together, the findings reveal that cell signaling pathways mediated by acetylation, methylation, and phosphorylation regulate the cytoskeleton, membrane traffic, and RNA binding protein-mediated control of gene expression. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Efficient Cancer Detection Using Multiple Neural Networks.

Science.gov (United States)

Shell, John; Gregory, William D

2017-01-01

The inspection of live excised tissue specimens to ascertain malignancy is a challenging task in dermatopathology and generally in histopathology. We introduce a portable desktop prototype device that provides highly accurate neural network classification of malignant and benign tissue. The handheld device collects 47 impedance data samples from 1 Hz to 32 MHz via tetrapolar blackened platinum electrodes. The data analysis was implemented with six different backpropagation neural networks (BNN). A data set consisting of 180 malignant and 180 benign breast tissue data files in an approved IRB study at the Aurora Medical Center, Milwaukee, WI, USA, were utilized as a neural network input. The BNN structure consisted of a multi-tiered consensus approach autonomously selecting four of six neural networks to determine a malignant or benign classification. The BNN analysis was then compared with the histology results with consistent sensitivity of 100% and a specificity of 100%. This implementation successfully relied solely on statistical variation between the benign and malignant impedance data and intricate neural network configuration. This device and BNN implementation provides a novel approach that could be a valuable tool to augment current medical practice assessment of the health of breast, squamous, and basal cell carcinoma and other excised tissue without requisite tissue specimen expertise. It has the potential to provide clinical management personnel with a fast non-invasive accurate assessment of biopsied or sectioned excised tissue in various clinical settings.

Molecular biology of breast cancer metastasis Molecular expression of vascular markers by aggressive breast cancer cells

International Nuclear Information System (INIS)

Hendrix, Mary JC; Seftor, Elisabeth A; Kirschmann, Dawn A; Seftor, Richard EB

2000-01-01

During embryogenesis, the formation of primary vascular networks occurs via the processes of vasculogenesis and angiogenesis. In uveal melanoma, vasculogenic mimicry describes the 'embryonic-like' ability of aggressive, but not nonaggressive, tumor cells to form networks surrounding spheroids of tumor cells in three-dimensional culture; these recapitulate the patterned networks seen in patients' aggressive tumors and correlates with poor prognosis. The molecular profile of these aggressive tumor cells suggests that they have a deregulated genotype, capable of expressing vascular phenotypes. Similarly, the embryonic-like phenotype expressed by the aggressive human breast cancer cells is associated with their ability to express a variety of vascular markers. These studies may offer new insights for consideration in breast cancer diagnosis and therapeutic intervention strategies

Singapore Cancer Network (SCAN) Guidelines for the Initial Evaluation, Diagnosis, and Management of Extremity Soft Tissue Sarcoma and Osteosarcoma.

Science.gov (United States)

2015-10-01

The SCAN sarcoma workgroup aimed to develop Singapore Cancer Network (SCAN) clinical practice guidelines for the initial evaluation, diagnosis, and management of extremity soft tissue sarcoma and osteosarcoma. The workgroup utilised a consensus approach to create high quality evidence-based clinical practice guidelines suited for our local setting. Various international guidelines from the fields of radiology, pathology, orthopaedic surgery, medical, radiation and paediatric oncology were reviewed, including those developed by von Mehren Metal (J Natl Compr Canc Netw 2014), the National Collaborating Centre for Cancer (2006), the European Sarcoma Network Working Group (2012) and Grimer RJ et al (Sarcoma 2008). Our clinical practice guidelines contextualised to the local patient will streamline care and improve clinical outcomes for patients with extremity soft tissue and osteosarcoma. These guidelines form the SCAN Guidelines 2015 for the initial evaluation, diagnosis, and management of extremity soft tissue sarcoma and osteosarcoma.

NCI National Clinical Trials Network Structure

Science.gov (United States)

Learn about how the National Clinical Trials Network (NCTN) is structured. The NCTN is a program of the National Cancer Institute that gives funds and other support to cancer research organizations to conduct cancer clinical trials.

Clinician-led improvement in cancer care (CLICC) - testing a multifaceted implementation strategy to increase evidence-based prostate cancer care: phased randomised controlled trial - study protocol

Science.gov (United States)

2014-01-01

mechanisms of change. Discussion The study will be one of the first randomised controlled trials to test the effectiveness of clinical networks to lead changes in clinical practice in hospitals treating patients with high-risk cancer. It will additionally provide direction regarding implementation strategies that can be effectively employed to encourage widespread adoption of clinical practice guidelines. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12611001251910. PMID:24884877

Integration of Pathway Knowledge and Dynamic Bayesian Networks for the Prediction of Oral Cancer Recurrence.

Science.gov (United States)

Kourou, Konstantina; Papaloukas, Costas; Fotiadis, Dimitrios I

2017-03-01

Oral squamous cell carcinoma has been characterized as a complex disease which involves dynamic genomic changes at the molecular level. These changes indicate the worth to explore the interactions of the molecules and especially of differentially expressed genes that contribute to cancer progression. Moreover, based on this knowledge the identification of differentially expressed genes and related molecular pathways is of great importance. In the present study, we exploit differentially expressed genes in order to further perform pathway enrichment analysis. According to our results we found significant pathways in which the disease associated genes have been identified as strongly enriched. Furthermore, based on the results of the pathway enrichment analysis we propose a methodology for predicting oral cancer recurrence using dynamic Bayesian networks. The methodology takes into consideration time series gene expression data in order to predict a disease recurrence. Subsequently, we are able to conjecture about the causal interactions between genes in consecutive time intervals. Concerning the performance of the predictive models, the overall accuracy of the algorithm is 81.8% and the area under the ROC curve 89.2% regarding the knowledge from the overrepresented pre-NOTCH Expression and processing pathway.

Network Approach in Political Communication Studies

Directory of Open Access Journals (Sweden)

Нина Васильевна Опанасенко

2013-12-01

Full Text Available The article is devoted to issues of network approach application in political communication studies. The author considers communication in online and offline areas and gives the definition of rhizome, its characteristics, identifies links between rhizome and network approach. The author also analyses conditions and possibilities of the network approach in modern political communication. Both positive and negative features of the network approach are emphasized.

Studying Dynamics in Business Networks

DEFF Research Database (Denmark)

Andersen, Poul Houman; Anderson, Helen; Havila, Virpi

1998-01-01

This paper develops a theory on network dynamics using the concepts of role and position from sociological theory. Moreover, the theory is further tested using case studies from Denmark and Finland......This paper develops a theory on network dynamics using the concepts of role and position from sociological theory. Moreover, the theory is further tested using case studies from Denmark and Finland...

Statistical Power in Longitudinal Network Studies

NARCIS (Netherlands)

Stadtfeld, Christoph; Snijders, Tom A. B.; Steglich, Christian; van Duijn, Marijtje

2018-01-01

Longitudinal social network studies may easily suffer from a lack of statistical power. This is the case in particular for studies that simultaneously investigate change of network ties and change of nodal attributes. Such selection and influence studies have become increasingly popular due to the

National Native American Breast Cancer Survivor's Network

National Research Council Canada - National Science Library

Burhansstipanov, Linda

2002-01-01

.... The purpose of this project is to improve the survival from breast cancer and quality of life after being diagnosed with breast cancer for both the patient and loved ones of the cancer patient...

National Native American Breast Cancer Survivor's Network

National Research Council Canada - National Science Library

Burhansstipanov, Linda

2003-01-01

.... The purpose of this project is to improve the survival from breast cancer and quality of life after being diagnosed with breast cancer for both the patient and loved ones of the cancer patient...

Comparative effects of different enteral feeding methods in head and neck cancer patients receiving radiotherapy or chemoradiotherapy: a network meta-analysis

Directory of Open Access Journals (Sweden)

Zhang ZH

2016-05-01

Full Text Available Zhihong Zhang,1,2 Yu Zhu,1 Yun Ling,3 Lijuan Zhang,1 Hongwei Wan1 1Department of Nursing, Shanghai Proton and Heavy Ion Center, 2Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, 3Department of Human Resource, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of China Abstract: Nasogastric tube (NGT and percutaneous endoscopic gastrostomy were frequently used in the head and neck cancer patients when malnutrition was present. Nevertheless, the evidence was inclusive in terms of the choice and the time of tube placement. The aim of this network meta-analysis was to evaluate the comparative effects of prophylactic percutaneous endoscopic gastrostomy (pPEG, reactive percutaneous endoscopic gastrostomy (rPEG, and NGT in the head and neck cancer patients receiving radiotherapy or chemoradiotherapy. Databases of PubMed, Web of Science, and Elsevier were searched from inception to October 2015. Thirteen studies enrolling 1,631 participants were included in this network meta-analysis. The results indicated that both pPEG and NGT were superior to rPEG in the management of weight loss. pPEG was associated with the least rate of treatment interruption and nutrition-related hospital admission among pPEG, rPEG, and NGT. Meanwhile, there was no difference in tube-related complications. Our study suggested that pPEG might be a better choice in malnutrition management in the head and neck cancer patients undergoing radiotherapy or chemoradiotherapy. However, its effects need to be further investigated in more randomized controlled trials. Keywords: malnutrition, tube feeding, weight loss, treatment interruption, readmission, complication

Italian cancer figures, report 2009: Cancer trend (1998-2005).

Science.gov (United States)

2009-01-01

the aim of this collaborative project of the Italian Network of Cancer Registries (Airtum; www.registri-tumori.it) was to analyse cancer incidence and mortality trends in Italy with special reference to the period 1998-2005. the study was based on the Airtum database, which collects and checks data from all the Airtum registries. The present study was based on 20 general and 2 specific populationbased cancer registries. Overall, we analysed 818,017 incident cases and 342,444 cancer deaths for the time period 1998-2005. Seventy percent of the analysed population was from the North of Italy, 17% from the Centre, and 13% from the South. A joinpoint analysis was carried out to detect the point in time where the trend changed; trends are described by means of the estimated annual percent change (APC), with appropriate 95% confidence intervals. Crude and standardized incidence and mortality rates were computed for 36 cancer sites, for both sexes, three age-classes (0-49, 50-69 and 70+ years), and three geographic areas (North, Centre, and South of Italy). Specific chapters are devoted to long-term trends (1986-2005), differences among age-groups, and international comparisons. In 1998-2005, cancer mortality for all sites showed a statistically significant decrease among men (APC - 1.7) and women (- 0.8). Mortality significantly decreased in both sexes for stomach cancer, rectum cancer, liver cancer, and Hodgkin lymphoma. Mortality also decreased among men for cancers of the upper aerodigestive tract, oesophagus, lung, prostate, urinary bladder, and leukaemia. Among women mortality decreased for cancers of the colon, bone, breast, and uterus not otherwise specified. An increase in mortality was recorded for lung cancer among women (+1.5) and melanoma among men (+2.6). Incidence for all cancers together (except non-melanoma skin cancers) increased among men (APC +0.3) and remained stable among women. Cancer sites which showed increasing incidence were thyroid and melanoma

Role of Chemokine Network in the Development and Progression of Ovarian Cancer: A Potential Novel Pharmacological Target

Directory of Open Access Journals (Sweden)

Federica Barbieri

2010-01-01

Full Text Available Ovarian cancer is the most common type of gynecologic malignancy. Despite advances in surgery and chemotherapy, the survival rate is still low since most ovarian cancers relapse and become drug-resistant. Chemokines are small chemoattractant peptides mainly involved in the immune responses. More recently, chemokines were also demonstrated to regulate extra-immunological functions. It was shown that the chemokine network plays crucial functions in the tumorigenesis in several tissues. In particular the imbalanced or aberrant expression of CXCL12 and its receptor CXCR4 strongly affects cancer cell proliferation, recruitment of immunosuppressive cells, neovascularization, and metastasization. In the last years, several molecules able to target CXCR4 or CXCL12 have been developed to interfere with tumor growth, including pharmacological inhibitors, antagonists, and specific antibodies. This chemokine ligand/receptor pair was also proposed to represent an innovative therapeutic target for the treatment of ovarian cancer. Thus, a thorough understanding of ovarian cancer biology, and how chemokines may control these different biological activities might lead to the development of more effective therapies. This paper will focus on the current biology of CXCL12/CXCR4 axis in the context of understanding their potential role in ovarian cancer development.

Combining PubMed knowledge and EHR data to develop a weighted bayesian network for pancreatic cancer prediction.

Science.gov (United States)

Zhao, Di; Weng, Chunhua

2011-10-01

In this paper, we propose a novel method that combines PubMed knowledge and Electronic Health Records to develop a weighted Bayesian Network Inference (BNI) model for pancreatic cancer prediction. We selected 20 common risk factors associated with pancreatic cancer and used PubMed knowledge to weigh the risk factors. A keyword-based algorithm was developed to extract and classify PubMed abstracts into three categories that represented positive, negative, or neutral associations between each risk factor and pancreatic cancer. Then we designed a weighted BNI model by adding the normalized weights into a conventional BNI model. We used this model to extract the EHR values for patients with or without pancreatic cancer, which then enabled us to calculate the prior probabilities for the 20 risk factors in the BNI. The software iDiagnosis was designed to use this weighted BNI model for predicting pancreatic cancer. In an evaluation using a case-control dataset, the weighted BNI model significantly outperformed the conventional BNI and two other classifiers (k-Nearest Neighbor and Support Vector Machine). We conclude that the weighted BNI using PubMed knowledge and EHR data shows remarkable accuracy improvement over existing representative methods for pancreatic cancer prediction. Copyright © 2011 Elsevier Inc. All rights reserved.

Collaborating to Move Research Forward: Proceedings of the 10th Annual Bladder Cancer Think Tank.

Science.gov (United States)

Kamat, Ashish M; Agarwal, Piyush; Bivalacqua, Trinity; Chisolm, Stephanie; Daneshmand, Sia; Doroshow, James H; Efstathiou, Jason A; Galsky, Matthew; Iyer, Gopa; Kassouf, Wassim; Shah, Jay; Taylor, John; Williams, Stephen B; Quale, Diane Zipursky; Rosenberg, Jonathan E

2016-04-27

The 10th Annual Bladder Cancer Think Tank was hosted by the Bladder Cancer Advocacy Network and brought together a multidisciplinary group of clinicians, researchers, representatives and Industry to advance bladder cancer research efforts. Think Tank expert panels, group discussions, and networking opportunities helped generate ideas and strengthen collaborations between researchers and physicians across disciplines and between institutions. Interactive panel discussions addressed a variety of timely issues: 1) data sharing, privacy and social media; 2) improving patient navigation through therapy; 3) promising developments in immunotherapy; 4) and moving bladder cancer research from bench to bedside. Lastly, early career researchers presented their bladder cancer studies and had opportunities to network with leading experts.

SentiHealth-Cancer: A sentiment analysis tool to help detecting mood of patients in online social networks.

Science.gov (United States)

Rodrigues, Ramon Gouveia; das Dores, Rafael Marques; Camilo-Junior, Celso G; Rosa, Thierson Couto

2016-01-01

Cancer is a critical disease that affects millions of people and families around the world. In 2012 about 14.1 million new cases of cancer occurred globally. Because of many reasons like the severity of some cases, the side effects of some treatments and death of other patients, cancer patients tend to be affected by serious emotional disorders, like depression, for instance. Thus, monitoring the mood of the patients is an important part of their treatment. Many cancer patients are users of online social networks and many of them take part in cancer virtual communities where they exchange messages commenting about their treatment or giving support to other patients in the community. Most of these communities are of public access and thus are useful sources of information about the mood of patients. Based on that, Sentiment Analysis methods can be useful to automatically detect positive or negative mood of cancer patients by analyzing their messages in these online communities. The objective of this work is to present a Sentiment Analysis tool, named SentiHealth-Cancer (SHC-pt), that improves the detection of emotional state of patients in Brazilian online cancer communities, by inspecting their posts written in Portuguese language. The SHC-pt is a sentiment analysis tool which is tailored specifically to detect positive, negative or neutral messages of patients in online communities of cancer patients. We conducted a comparative study of the proposed method with a set of general-purpose sentiment analysis tools adapted to this context. Different collections of posts were obtained from two cancer communities in Facebook. Additionally, the posts were analyzed by sentiment analysis tools that support the Portuguese language (Semantria and SentiStrength) and by the tool SHC-pt, developed based on the method proposed in this paper called SentiHealth. Moreover, as a second alternative to analyze the texts in Portuguese, the collected texts were automatically translated

Oral cancer: A multicenter study

Science.gov (United States)

Rojanawatsirivej, Somsri; Thosaporn, Watcharaporn; Kintarak, Sompid; Subarnbhesaj, Ajiravudh; Darling, Mark; Kryshtalskyj, Eugene; Chiang, Chun-Pin; Shin, Hong-In; Choi, So-Young; Lee, Sang-shin; Shakib, Pouyan-Amini

2018-01-01

Background To determine the prevalence and clinicopathologic features of the oral cancer patients. Material and Methods Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. Results Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Conclusions Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as

Negative cancer stereotypes and disease-specific self-concept in head and neck cancer.

Science.gov (United States)

Wong, Janice C; Payne, Ada Y M; Mah, Kenneth; Lebel, Sophie; Lee, Ruth N F; Irish, Jonathan; Rodin, Gary; Devins, Gerald M

2013-05-01

Life-threatening diseases, such as head and neck cancer (HNCa), can stimulate the emergence of a new disease-specific self-concept. We hypothesized that (i) negative cancer-stereotypes invoke distancing, which inhibits the adoption of a disease-specific self-concept and (ii) patient characteristics, disease and treatment factors, and cancer-related stressors moderate the phenomenon. Head and neck cancer outpatients (N = 522) completed a semantic-differential measure of disease-specific self-concept (perceived similarity to the 'cancer patient') and other self-report measures in structured interviews. Negative cancer-stereotypes were represented by the number of semantic-differential dimensions (0-3) along which respondents evaluated the stereotypic 'cancer patient' negatively (i.e., negative valence). We tested the two-way interactions between negative valence and hypothesized moderator variables. We observed significant negative valence × moderator interactions for the following: (i) patient characteristics (education, employment, social networks); (ii) disease and treatment factors (cancer-symptom burden); and (iii) cancer-related stressors (uncertainty, lack of information, and existential threats). Negative cancer stereotypes were consistently associated with distancing of self from the stereotypic 'cancer patient,' but the effect varied across moderator variables. All significant moderators (except employment and social networks) were associated with increasing perceived similarity to the 'cancer patient' when respondents maintained negative stereotypes; perceived similarity decreased when people were employed or had extensive social networks. Moderator effects were less pronounced when respondents did not endorse negative cancer stereotypes. When they hold negative stereotypes, people with HNCa distance themselves from a 'cancer patient' identity to preserve self-esteem or social status, but exposure to cancer-related stressors and adaptive demands may

Privacy Practices of Health Social Networking Sites: Implications for Privacy and Data Security in Online Cancer Communities.

Science.gov (United States)

Charbonneau, Deborah H

2016-08-01

While online communities for social support continue to grow, little is known about the state of privacy practices of health social networking sites. This article reports on a structured content analysis of privacy policies and disclosure practices for 25 online ovarian cancer communities. All of the health social networking sites in the study sample provided privacy statements to users, yet privacy practices varied considerably across the sites. The majority of sites informed users that personal information was collected about participants and shared with third parties (96%, n = 24). Furthermore, more than half of the sites (56%, n = 14) stated that cookies technology was used to track user behaviors. Despite these disclosures, only 36% (n = 9) offered opt-out choices for sharing data with third parties. In addition, very few of the sites (28%, n = 7) allowed individuals to delete their personal information. Discussions about specific security measures used to protect personal information were largely missing. Implications for privacy, confidentiality, consumer choice, and data safety in online environments are discussed. Overall, nurses and other health professionals can utilize these findings to encourage individuals seeking online support and participating in social networking sites to build awareness of privacy risks to better protect their personal health information in the digital age.

How Effective Are Clinical Pathways With and Without Online Peer-Review? An Analysis of Bone Metastases Pathway in a Large, Integrated National Cancer Institute-Designated Comprehensive Cancer Center Network

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Beriwal, Sushil, E-mail: beriwals@upmc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rajagopalan, Malolan S.; Flickinger, John C.; Rakfal, Susan M. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Rodgers, Edwin [Via Oncology, Pittsburgh, PA (United States); Heron, Dwight E. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA (United States)

2012-07-15

Purpose: Clinical pathways are an important tool used to manage the quality in health care by standardizing processes. This study evaluated the impact of the implementation of a peer-reviewed clinical pathway in a large, integrated National Cancer Institute-Designated Comprehensive Cancer Center Network. Methods: In 2003, we implemented a clinical pathway for the management of bone metastases with palliative radiation therapy. In 2009, we required the entry of management decisions into an online tool that records pathway choices. The pathway specified 1 or 5 fractions for symptomatic bone metastases with the option of 10-14 fractions for certain clinical situations. The data were obtained from 13 integrated sites (3 central academic, 10 community locations) from 2003 through 2010. Results: In this study, 7905 sites were treated with 64% of courses delivered in community practice and 36% in academic locations. Academic practices were more likely than community practices to treat with 1-5 fractions (63% vs. 23%; p < 0.0001). The number of delivered fractions decreased gradually from 2003 to 2010 for both academic and community practices (p < 0.0001); however, greater numbers of fractions were selected more often in community practices (p < 0.0001). Using multivariate logistic regression, we found that a significantly greater selection of 1-5 fractions developed after implementation online pathway monitoring (2009) with an odds ratio of 1.2 (confidence interval, 1.1-1.4) for community and 1.3 (confidence interval, 1.1-1.6) for academic practices. The mean number of fractions also decreased after online peer review from 6.3 to 6.0 for academic (p = 0.07) and 9.4 to 9.0 for community practices (p < 0.0001). Conclusion: This is one of the first studies to examine the efficacy of a clinical pathway for radiation oncology in an integrated cancer network. Clinical pathway implementation appears to be effective in changing patterns of care, particularly with online clinical

How Effective Are Clinical Pathways With and Without Online Peer-Review? An Analysis of Bone Metastases Pathway in a Large, Integrated National Cancer Institute–Designated Comprehensive Cancer Center Network

International Nuclear Information System (INIS)

Beriwal, Sushil; Rajagopalan, Malolan S.; Flickinger, John C.; Rakfal, Susan M.; Rodgers, Edwin; Heron, Dwight E.

2012-01-01

Purpose: Clinical pathways are an important tool used to manage the quality in health care by standardizing processes. This study evaluated the impact of the implementation of a peer-reviewed clinical pathway in a large, integrated National Cancer Institute–Designated Comprehensive Cancer Center Network. Methods: In 2003, we implemented a clinical pathway for the management of bone metastases with palliative radiation therapy. In 2009, we required the entry of management decisions into an online tool that records pathway choices. The pathway specified 1 or 5 fractions for symptomatic bone metastases with the option of 10–14 fractions for certain clinical situations. The data were obtained from 13 integrated sites (3 central academic, 10 community locations) from 2003 through 2010. Results: In this study, 7905 sites were treated with 64% of courses delivered in community practice and 36% in academic locations. Academic practices were more likely than community practices to treat with 1–5 fractions (63% vs. 23%; p < 0.0001). The number of delivered fractions decreased gradually from 2003 to 2010 for both academic and community practices (p < 0.0001); however, greater numbers of fractions were selected more often in community practices (p < 0.0001). Using multivariate logistic regression, we found that a significantly greater selection of 1–5 fractions developed after implementation online pathway monitoring (2009) with an odds ratio of 1.2 (confidence interval, 1.1–1.4) for community and 1.3 (confidence interval, 1.1–1.6) for academic practices. The mean number of fractions also decreased after online peer review from 6.3 to 6.0 for academic (p = 0.07) and 9.4 to 9.0 for community practices (p < 0.0001). Conclusion: This is one of the first studies to examine the efficacy of a clinical pathway for radiation oncology in an integrated cancer network. Clinical pathway implementation appears to be effective in changing patterns of care, particularly with

Complications of stent placement in patients with esophageal cancer: A systematic review and network meta-analysis.

Directory of Open Access Journals (Sweden)

Amin Doosti-Irani

Full Text Available Palliative treatments and stents are necessary for relieving dysphagia in patients with esophageal cancer. The aim of this study was to simultaneously compare available treatments in terms of complications.Web of Science, Medline, Scopus, Cochrane Library and Embase were searched. Statistical heterogeneity was assessed using the Chi2 test and was quantified by I2. The results of this study were summarized in terms of Risk Ratio (RR. The random effects model was used to report the results. The rank probability for each treatment was calculated using the p-score.Out of 17855 references, 24 RCTs reported complications including treatment related death (TRD, bleeding, stent migration, aspiration, severe pain and fistula formation. In the ranking of treatments, thermal ablative therapy (p-score = 0.82, covered Evolution® stent (p-score = 0.70, brachytherapy (p-score = 0.72 and antireflux stent (p-score = 0.74 were better treatments in the network of TRD. Thermal ablative therapy (p-score = 0.86, the conventional stent (p-score = 0.62, covered Evolution® stent (p-score = 0.96 and brachytherapy (p-score = 0.82 were better treatments in the network of bleeding complications. Covered Evolution® (p-score = 0.78, uncovered (p-score = 0.88 and irradiation stents (p-score = 0.65 were better treatments in network of stent migration complications. In the network of severe pain, Conventional self-expandable nitinol alloy covered stent (p-score = 0.73, polyflex (p-score = 0.79, latex prosthesis (p-score = 0.96 and brachytherapy (p-score = 0.65 were better treatments.According to our results, thermal ablative therapy, covered Evolution® stents, brachytherapy, and antireflux stents are associated with a lower risk of TRD. Moreover, thermal ablative therapy, conventional, covered Evolution® and brachytherapy had lower risks of bleeding. Overall, fewer complications were associated with covered Evolution® stent and brachytherapy.

Complications of stent placement in patients with esophageal cancer: A systematic review and network meta-analysis

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Doosti-Irani, Amin; Mansournia, Mohammad Ali; Rahimi-Foroushani, Abbas; Haddad, Peiman

2017-01-01

Background Palliative treatments and stents are necessary for relieving dysphagia in patients with esophageal cancer. The aim of this study was to simultaneously compare available treatments in terms of complications. Methods Web of Science, Medline, Scopus, Cochrane Library and Embase were searched. Statistical heterogeneity was assessed using the Chi2 test and was quantified by I2. The results of this study were summarized in terms of Risk Ratio (RR). The random effects model was used to report the results. The rank probability for each treatment was calculated using the p-score. Results Out of 17855 references, 24 RCTs reported complications including treatment related death (TRD), bleeding, stent migration, aspiration, severe pain and fistula formation. In the ranking of treatments, thermal ablative therapy (p-score = 0.82), covered Evolution® stent (p-score = 0.70), brachytherapy (p-score = 0.72) and antireflux stent (p-score = 0.74) were better treatments in the network of TRD. Thermal ablative therapy (p-score = 0.86), the conventional stent (p-score = 0.62), covered Evolution® stent (p-score = 0.96) and brachytherapy (p-score = 0.82) were better treatments in the network of bleeding complications. Covered Evolution® (p-score = 0.78), uncovered (p-score = 0.88) and irradiation stents (p-score = 0.65) were better treatments in network of stent migration complications. In the network of severe pain, Conventional self-expandable nitinol alloy covered stent (p-score = 0.73), polyflex (p-score = 0.79), latex prosthesis (p-score = 0.96) and brachytherapy (p-score = 0.65) were better treatments. Conclusion According to our results, thermal ablative therapy, covered Evolution® stents, brachytherapy, and antireflux stents are associated with a lower risk of TRD. Moreover, thermal ablative therapy, conventional, covered Evolution® and brachytherapy had lower risks of bleeding. Overall, fewer complications were associated with covered Evolution® stent and

Integrating text mining, data mining, and network analysis for identifying genetic breast cancer trends.

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Jurca, Gabriela; Addam, Omar; Aksac, Alper; Gao, Shang; Özyer, Tansel; Demetrick, Douglas; Alhajj, Reda

2016-04-26

Breast cancer is a serious disease which affects many women and may lead to death. It has received considerable attention from the research community. Thus, biomedical researchers aim to find genetic biomarkers indicative of the disease. Novel biomarkers can be elucidated from the existing literature. However, the vast amount of scientific publications on breast cancer make this a daunting task. This paper presents a framework which investigates existing literature data for informative discoveries. It integrates text mining and social network analysis in order to identify new potential biomarkers for breast cancer. We utilized PubMed for the testing. We investigated gene-gene interactions, as well as novel interactions such as gene-year, gene-country, and abstract-country to find out how the discoveries varied over time and how overlapping/diverse are the discoveries and the interest of various research groups in different countries. Interesting trends have been identified and discussed, e.g., different genes are highlighted in relationship to different countries though the various genes were found to share functionality. Some text analysis based results have been validated against results from other tools that predict gene-gene relations and gene functions.

A network-based method to evaluate quality of reproducibility of differential expression in cancer genomics studies.

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Li, Robin; Lin, Xiao; Geng, Haijiang; Li, Zhihui; Li, Jiabing; Lu, Tao; Yan, Fangrong

2015-12-29

Personalized cancer treatments depend on the determination of a patient's genetic status according to known genetic profiles for which targeted treatments exist. Such genetic profiles must be scientifically validated before they is applied to general patient population. Reproducibility of findings that support such genetic profiles is a fundamental challenge in validation studies. The percentage of overlapping genes (POG) criterion and derivative methods produce unstable and misleading results. Furthermore, in a complex disease, comparisons between different tumor subtypes can produce high POG scores that do not capture the consistencies in the functions. We focused on the quality rather than the quantity of the overlapping genes. We defined the rank value of each gene according to importance or quality by PageRank on basis of a particular topological structure. Then, we used the p-value of the rank-sum of the overlapping genes (PRSOG) to evaluate the quality of reproducibility. Though the POG scores were low in different studies of the same disease, the PRSOG was statistically significant, which suggests that sets of differentially expressed genes might be highly reproducible. Evaluations of eight datasets from breast cancer, lung cancer and four other disorders indicate that quality-based PRSOG method performs better than a quantity-based method. Our analysis of the components of the sets of overlapping genes supports the utility of the PRSOG method.

Epidemiologic study of uterine cancer, Hiroshima

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Ishimaru, Toranosuke

1965-12-10

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

Dissortativity and duplications in oral cancer

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Shinde, Pramod; Yadav, Alok; Rai, Aparna; Jalan, Sarika

2015-08-01

More than 300 000 new cases worldwide are being diagnosed with oral cancer annually. Complexity of oral cancer renders designing drug targets very difficult. We analyse protein-protein interaction network for the normal and oral cancer tissue and detect crucial changes in the structural properties of the networks in terms of the interactions of the hub proteins and the degree-degree correlations. Further analysis of the spectra of both the networks, while exhibiting universal statistical behaviour, manifest distinction in terms of the zero degeneracy, providing insight to the complexity of the underlying system.

Reducing time-to-treatment in underserved Latinas with breast cancer: the Six Cities Study.

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Ramirez, Amelie; Perez-Stable, Eliseo; Penedo, Frank; Talavera, Gregory; Carrillo, J Emilio; Fernández, María; Holden, Alan; Munoz, Edgar; San Miguel, Sandra; Gallion, Kipling

2014-03-01

The interaction of clinical and patient-level challenges following a breast cancer diagnosis can be a significant source of health care disparities. Failure to address specific cultural features that create or exacerbate barriers can lead to less-than optimal navigation results, specifically in Hispanic/Latino women. To address these disparities, the study leaders in San Antonio, Texas, and 5 other regional partners of the federally-funded Redes En Acción: The National Latino Cancer Research Network developed a culturally-tailored patient navigation intervention model for Latinas with breast cancer. Compared with control patients, a higher percentage of navigated subjects initiated treatment within 30 days (69.0% versus 46.3%, P = .029) and 60 days (97.6% versus 73.1%, P = .001) following their cancer diagnosis. Time from cancer diagnosis to first treatment was lower in the navigated group (mean, 22.22 days; median, 23.00 days) than controls (mean, 48.30 days; median, 33.00 days). These results were independent of cancer stage at diagnosis and numerous characteristics of cancer clinics and individual participants. Successful application of patient navigation increased the percentage of Latinas initiating breast cancer treatment within 30 and 60 days of diagnosis. This was achieved through navigator provision of services such as accompaniment to appointments, transportation arrangements, patient telephone support, patient-family telephone support, Spanish-English language translation, and assistance with insurance paperwork. © 2013 American Cancer Society.

What are artificial neural networks?

DEFF Research Database (Denmark)

Krogh, Anders

2008-01-01

Artificial neural networks have been applied to problems ranging from speech recognition to prediction of protein secondary structure, classification of cancers and gene prediction. How do they work and what might they be good for? Udgivelsesdato: 2008-Feb......Artificial neural networks have been applied to problems ranging from speech recognition to prediction of protein secondary structure, classification of cancers and gene prediction. How do they work and what might they be good for? Udgivelsesdato: 2008-Feb...

The Integrative Method Based on the Module-Network for Identifying Driver Genes in Cancer Subtypes

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Xinguo Lu

2018-01-01

Full Text Available With advances in next-generation sequencing(NGS technologies, a large number of multiple types of high-throughput genomics data are available. A great challenge in exploring cancer progression is to identify the driver genes from the variant genes by analyzing and integrating multi-types genomics data. Breast cancer is known as a heterogeneous disease. The identification of subtype-specific driver genes is critical to guide the diagnosis, assessment of prognosis and treatment of breast cancer. We developed an integrated frame based on gene expression profiles and copy number variation (CNV data to identify breast cancer subtype-specific driver genes. In this frame, we employed statistical machine-learning method to select gene subsets and utilized an module-network analysis method to identify potential candidate driver genes. The final subtype-specific driver genes were acquired by paired-wise comparison in subtypes. To validate specificity of the driver genes, the gene expression data of these genes were applied to classify the patient samples with 10-fold cross validation and the enrichment analysis were also conducted on the identified driver genes. The experimental results show that the proposed integrative method can identify the potential driver genes and the classifier with these genes acquired better performance than with genes identified by other methods.

Record linkage for pharmacoepidemiological studies in cancer patients.

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Herk-Sukel, Myrthe P P van; Lemmens, Valery E P P; Poll-Franse, Lonneke V van de; Herings, Ron M C; Coebergh, Jan Willem W

2012-01-01

An increasing need has developed for the post-approval surveillance of (new) anti-cancer drugs by means of pharmacoepidemiology and outcomes research in the area of oncology. To create an overview that makes researchers aware of the available database linkages in Northern America and Europe which facilitate pharmacoepidemiology and outcomes research in cancer patients. In addition to our own database, i.e. the Eindhoven Cancer Registry (ECR) linked to the PHARMO Record Linkage System, we considered database linkages between a population-based cancer registry and an administrative healthcare database that at least contains information on drug use and offers a longitudinal perspective on healthcare utilization. Eligible database linkages were limited to those that had been used in multiple published articles in English language included in Pubmed. The HMO Cancer Research Network (CRN) in the US was excluded from this review, as an overview of the linked databases participating in the CRN is already provided elsewhere. Researchers who had worked with the data resources included in our review were contacted for additional information and verification of the data presented in the overview. The following database linkages were included: the Surveillance, Epidemiology, and End-Results-Medicare; cancer registry data linked to Medicaid; Canadian cancer registries linked to population-based drug databases; the Scottish cancer registry linked to the Tayside drug dispensing data; linked databases in the Nordic Countries of Europe: Norway, Sweden, Finland and Denmark; and the ECR-PHARMO linkage in the Netherlands. Descriptives of the included database linkages comprise population size, generalizability of the population, year of first data availability, contents of the cancer registry, contents of the administrative healthcare database, the possibility to select a cancer-free control cohort, and linkage to other healthcare databases. The linked databases offer a longitudinal

A Bayesian network approach for modeling local failure in lung cancer

International Nuclear Information System (INIS)

Oh, Jung Hun; Craft, Jeffrey; Al Lozi, Rawan; Vaidya, Manushka; Meng, Yifan; Deasy, Joseph O; Bradley, Jeffrey D; El Naqa, Issam

2011-01-01

Locally advanced non-small cell lung cancer (NSCLC) patients suffer from a high local failure rate following radiotherapy. Despite many efforts to develop new dose-volume models for early detection of tumor local failure, there was no reported significant improvement in their application prospectively. Based on recent studies of biomarker proteins' role in hypoxia and inflammation in predicting tumor response to radiotherapy, we hypothesize that combining physical and biological factors with a suitable framework could improve the overall prediction. To test this hypothesis, we propose a graphical Bayesian network framework for predicting local failure in lung cancer. The proposed approach was tested using two different datasets of locally advanced NSCLC patients treated with radiotherapy. The first dataset was collected retrospectively, which comprises clinical and dosimetric variables only. The second dataset was collected prospectively in which in addition to clinical and dosimetric information, blood was drawn from the patients at various time points to extract candidate biomarkers as well. Our preliminary results show that the proposed method can be used as an efficient method to develop predictive models of local failure in these patients and to interpret relationships among the different variables in the models. We also demonstrate the potential use of heterogeneous physical and biological variables to improve the model prediction. With the first dataset, we achieved better performance compared with competing Bayesian-based classifiers. With the second dataset, the combined model had a slightly higher performance compared to individual physical and biological models, with the biological variables making the largest contribution. Our preliminary results highlight the potential of the proposed integrated approach for predicting post-radiotherapy local failure in NSCLC patients.

Network Graph Analysis of Gene-Gene Interactions in Genome-Wide Association Study Data

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Sungyoung Lee

2012-12-01

Full Text Available Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs. For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR is one of the powerful and efficient methods for detecting high-order gene-gene (GxG interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI. Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

Network graph analysis of gene-gene interactions in genome-wide association study data.

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Lee, Sungyoung; Kwon, Min-Seok; Park, Taesung

2012-12-01

Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs). For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR) is one of the powerful and efficient methods for detecting high-order gene-gene (GxG) interactions. However, the biological interpretation of GxG interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified GxG interactions. The proposed network graph analysis consists of three steps. The first step is for performing GxG interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified GxG interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE) data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform GxG interaction analysis of body mass index (BMI). Our network graph analysis successfully showed that many identified GxG interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of GxG interactions.

[Strengthen the cancer surveillance to promote cancer prevention and control in China].

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He, J

2018-01-23

Cancer is a major chronic disease threatening the people's health in China. We reviewed the latest advances on cancer surveillance, prevention and control in our country, which may provide important clues for future cancer control. We used data from the National Central Cancer Registry, to describe and analyze the latest cancer statistics in China. We summarized updated informations on cancer control policies, conducting network, as well as programs in the country. We provided important suggestions on the future strategies of cancer prevention and control. The overall cancer burden in China has been increasing during the past decades. In 2014, there were about 3 804 000 new cancer cases and 2 296 000 cancer deaths in China. The age-standardized cancer incidence and mortality rates were 190.63/100 000 and 106.98/100 000, respectively. China has formed a comprehensive network on cancer prevention and control. Nationwide population-based cancer surveillance has been built up. The population coverage of cancer surveillance has been expanded, and the data quality has been improved. As the aging population is increasing and unhealthy life styles persist in our country, there will be an unnegligible cancer burden in China. Based on the comprehensive rationale of cancer control and prevention, National Cancer Center of China will perform its duty for future precise cancer control and prevention, based on cancer surveillance statistics.

A Physical Mechanism and Global Quantification of Breast Cancer.

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Chong Yu

Full Text Available Initiation and progression of cancer depend on many factors. Those on the genetic level are often considered crucial. To gain insight into the physical mechanisms of breast cancer, we construct a gene regulatory network (GRN which reflects both genetic and environmental aspects of breast cancer. The construction of the GRN is based on available experimental data. Three basins of attraction, representing the normal, premalignant and cancer states respectively, were found on the phenotypic landscape. The progression of breast cancer can be seen as switching transitions between different state basins. We quantified the stabilities and kinetic paths of the three state basins to uncover the biological process of breast cancer formation. The gene expression levels at each state were obtained, which can be tested directly in experiments. Furthermore, by performing global sensitivity analysis on the landscape topography, six key genes (HER2, MDM2, TP53, BRCA1, ATM, CDK2 and four regulations (HER2⊣TP53, CDK2⊣BRCA1, ATM→MDM2, TP53→ATM were identified as being critical for breast cancer. Interestingly, HER2 and MDM2 are the most popular targets for treating breast cancer. BRCA1 and TP53 are the most important oncogene of breast cancer and tumor suppressor gene, respectively. This further validates the feasibility of our model and the reliability of our prediction results. The regulation ATM→MDM2 has been extensive studied on DNA damage but not on breast cancer. We notice the importance of ATM→MDM2 on breast cancer. Previous studies of breast cancer have often focused on individual genes and the anti-cancer drugs are mainly used to target the individual genes. Our results show that the network-based strategy is more effective on treating breast cancer. The landscape approach serves as a new strategy for analyzing breast cancer on both the genetic and epigenetic levels and can help on designing network based medicine for breast cancer.

Personalized Network-Based Treatments in Oncology

DEFF Research Database (Denmark)

Robin, Xavier; Creixell, Pau; Radetskaya, Oxana

2013-01-01

Network medicine aims at unraveling cell signaling networks to propose personalized treatments for patients suffering from complex diseases. In this short review, we show the relevance of network medicine to cancer treatment by outlining the potential convergence points of the most recent technol...

AUTOMATED DETECTION OF MITOTIC FIGURES IN BREAST CANCER HISTOPATHOLOGY IMAGES USING GABOR FEATURES AND DEEP NEURAL NETWORKS

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Maqlin Paramanandam

2016-11-01

Full Text Available The count of mitotic figures in Breast cancer histopathology slides is the most significant independent prognostic factor enabling determination of the proliferative activity of the tumor. In spite of the strict protocols followed, the mitotic counting activity suffers from subjectivity and considerable amount of observer variability despite being a laborious task. Interest in automated detection of mitotic figures has been rekindled with the advent of Whole Slide Scanners. Subsequently mitotic detection grand challenge contests have been held in recent years and several research methodologies developed by their participants. This paper proposes an efficient mitotic detection methodology for Hematoxylin and Eosin stained Breast cancer Histopathology Images using Gabor features and a Deep Belief Network- Deep Neural Network architecture (DBN-DNN. The proposed method has been evaluated on breast histopathology images from the publicly available dataset from MITOS contest held at the ICPR 2012 conference. It contains 226 mitoses annotated on 35 HPFs by several pathologists and 15 testing HPFs, yielding an F-measure of 0.74. In addition the said methodology was also tested on 3 slides from the MITOSIS- ATYPIA grand challenge held at the ICPR 2014 conference, an extension of MITOS containing 749 mitoses annotated on 1200 HPFs, by pathologists worldwide. This study has employed 3 slides (294 HPFs from the MITOS-ATYPIA training dataset in its evaluation and the results showed F-measures 0.65, 0.72and 0.74 for each slide. The proposed method is fast and computationally simple yet its accuracy and specificity is comparable to the best winning methods of the aforementioned grand challenges

US-LA CRN Clinical Cancer Research in Latin America

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The United States – Latin America Cancer Research Network (US-LA CRN) convened its Annual Meeting, in coordination with the Ministry of Health of Chile to discuss the Network’s first multilateral clinical research study: Molecular Profiling of Breast Cancer (MPBC).

Hereditary association between testicular cancer and familial ovarian cancer: A Familial Ovarian Cancer Registry study.

Science.gov (United States)

Etter, John Lewis; Eng, Kevin; Cannioto, Rikki; Kaur, Jasmine; Almohanna, Hani; Alqassim, Emad; Szender, J Brian; Joseph, Janine M; Lele, Shashikant; Odunsi, Kunle; Moysich, Kirsten B

2018-04-01

Although family history of testicular cancer is well-established as a risk factor for testicular cancer, it is unknown whether family history of ovarian cancer is associated with risk of testicular cancer. Using data from the Familial Ovarian Cancer Registry on 2636 families with multiple cases of ovarian cancer, we systematically compared relative frequencies of ovarian cancer among relatives of men with testicular and non-testicular cancers. Thirty-one families with cases of both ovarian and testicular cancer were identified. We observed that, among men with cancer, those with testicular cancer were more likely to have a mother with ovarian cancer than those with non-testicular cancers (OR = 3.32, p = 0.004). Zero paternal grandmothers of men with testicular cancer had ovarian cancer. These observations provide compelling preliminary evidence for a familial association between ovarian and testicular cancers Future studies should be designed to further investigate this association and evaluate X-linkage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comprehensive Genomic Profiling Facilitates Implementation of the National Comprehensive Cancer Network Guidelines for Lung Cancer Biomarker Testing and Identifies Patients Who May Benefit From Enrollment in Mechanism-Driven Clinical Trials.

Science.gov (United States)

Suh, James H; Johnson, Adrienne; Albacker, Lee; Wang, Kai; Chmielecki, Juliann; Frampton, Garrett; Gay, Laurie; Elvin, Julia A; Vergilio, Jo-Anne; Ali, Siraj; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S

2016-06-01

The National Comprehensive Cancer Network (NCCN) guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for EGFR, BRAF, ERBB2, and MET mutations; ALK, ROS1, and RET rearrangements; and MET amplification. We investigated the feasibility and utility of comprehensive genomic profiling (CGP), a hybrid capture-based next-generation sequencing (NGS) test, in clinical practice. CGP was performed to a mean coverage depth of 576× on 6,832 consecutive cases of NSCLC (2012-2015). Genomic alterations (GAs) (point mutations, small indels, copy number changes, and rearrangements) involving EGFR, ALK, BRAF, ERBB2, MET, ROS1, RET, and KRAS were recorded. We also evaluated lung adenocarcinoma (AD) cases without GAs, involving these eight genes. The median age of the patients was 64 years (range: 13-88 years) and 53% were female. Among the patients studied, 4,876 (71%) harbored at least one GA involving EGFR (20%), ALK (4.1%), BRAF (5.7%), ERBB2 (6.0%), MET (5.6%), ROS1 (1.5%), RET (2.4%), or KRAS (32%). In the remaining cohort of lung AD without these known drivers, 273 cancer-related genes were altered in at least 0.1% of cases, including STK11 (21%), NF1 (13%), MYC (9.8%), RICTOR (6.4%), PIK3CA (5.4%), CDK4 (4.3%), CCND1 (4.0%), BRCA2 (2.5%), NRAS (2.3%), BRCA1 (1.7%), MAP2K1 (1.2%), HRAS (0.7%), NTRK1 (0.7%), and NTRK3 (0.2%). CGP is practical and facilitates implementation of the NCCN guidelines for NSCLC by enabling simultaneous detection of GAs involving all seven driver oncogenes and KRAS. Furthermore, without additional tissue use or cost, CGP identifies patients with "pan-negative" lung AD who may benefit from enrollment in mechanism-driven clinical trials. National Comprehensive Cancer Network guidelines for patients with metastatic non-small cell lung cancer (NSCLC) recommend testing for several genomic alterations (GAs). The feasibility and utility of comprehensive genomic profiling were studied in NSCLC and in lung adenocarcinoma

Patient-centered prioritization of bladder cancer research.

Science.gov (United States)

Smith, Angela B; Chisolm, Stephanie; Deal, Allison; Spangler, Alejandra; Quale, Diane Z; Bangs, Rick; Jones, J Michael; Gore, John L

2018-05-04

Patient-centered research requires the meaningful involvement of patients and caregivers throughout the research process. The objective of this study was to create a process for sustainable engagement for research prioritization within oncology. From December 2014 to 2016, a network of engaged patients for research prioritization was created in partnership with the Bladder Cancer Advocacy Network (BCAN): the BCAN Patient Survey Network (PSN). The PSN leveraged an online bladder cancer community with additional recruitment through print advertisements and social media campaigns. Prioritized research questions were developed through a modified Delphi process and were iterated through multidisciplinary working groups and a repeat survey. In year 1 of the PSN, 354 patients and caregivers responded to the research prioritization survey; the number of responses increased to 1034 in year 2. The majority of respondents had non-muscle-invasive bladder cancer (NMIBC), and the mean time since diagnosis was 5 years. Stakeholder-identified questions for noninvasive, invasive, and metastatic disease were prioritized by the PSN. Free-text questions were sorted with thematic mapping. Several questions submitted by respondents were among the prioritized research questions. A final prioritized list of research questions was disseminated to various funding agencies, and a highly ranked NMIBC research question was included as a priority area in the 2017 Patient-Centered Outcomes Research Institute announcement of pragmatic trial funding. Patient engagement is needed to identify high-priority research questions in oncology. The BCAN PSN provides a successful example of an engagement infrastructure for annual research prioritization in bladder cancer. The creation of an engagement network sets the groundwork for additional phases of engagement, including design, conduct, and dissemination. Cancer 2018. © 2018 American Cancer Society. © 2018 American Cancer Society.

Layered signaling regulatory networks analysis of gene expression involved in malignant tumorigenesis of non-resolving ulcerative colitis via integration of cross-study microarray profiles.

Science.gov (United States)

Fan, Shengjun; Pan, Zhenyu; Geng, Qiang; Li, Xin; Wang, Yefan; An, Yu; Xu, Yan; Tie, Lu; Pan, Yan; Li, Xuejun

2013-01-01

Ulcerative colitis (UC) was the most frequently diagnosed inflammatory bowel disease (IBD) and closely linked to colorectal carcinogenesis. By far, the underlying mechanisms associated with the disease are still unclear. With the increasing accumulation of microarray gene expression profiles, it is profitable to gain a systematic perspective based on gene regulatory networks to better elucidate the roles of genes associated with disorders. However, a major challenge for microarray data analysis is the integration of multiple-studies generated by different groups. In this study, firstly, we modeled a signaling regulatory network associated with colorectal cancer (CRC) initiation via integration of cross-study microarray expression data sets using Empirical Bayes (EB) algorithm. Secondly, a manually curated human cancer signaling map was established via comprehensive retrieval of the publicly available repositories. Finally, the co-differently-expressed genes were manually curated to portray the layered signaling regulatory networks. Overall, the remodeled signaling regulatory networks were separated into four major layers including extracellular, membrane, cytoplasm and nucleus, which led to the identification of five core biological processes and four signaling pathways associated with colorectal carcinogenesis. As a result, our biological interpretation highlighted the importance of EGF/EGFR signaling pathway, EPO signaling pathway, T cell signal transduction and members of the BCR signaling pathway, which were responsible for the malignant transition of CRC from the benign UC to the aggressive one. The present study illustrated a standardized normalization approach for cross-study microarray expression data sets. Our model for signaling networks construction was based on the experimentally-supported interaction and microarray co-expression modeling. Pathway-based signaling regulatory networks analysis sketched a directive insight into colorectal carcinogenesis

Campus network security model study

Science.gov (United States)

Zhang, Yong-ku; Song, Li-ren

2011-12-01

Campus network security is growing importance, Design a very effective defense hacker attacks, viruses, data theft, and internal defense system, is the focus of the study in this paper. This paper compared the firewall; IDS based on the integrated, then design of a campus network security model, and detail the specific implementation principle.

A holistic approach to study the effects of natural antioxidants on inflammation and liver cancer.

Science.gov (United States)

Costantini, Susan; Colonna, Giovanni; Castello, Giuseppe

2014-01-01

The limited effectiveness of chemotherapy and the high recurrence rate of cancers highlight the urgent need to identify new molecular targets and to develop new treatments. Numerous epidemiological studies have recently highlighted the existence of an inverse association between fruit and vegetable consumption, natural antioxidants, and cancer risk; in fact, antioxidant intake through diet or supplements of plant origin is strongly recommended for cancer prevention and cure. In general, antioxidants are substances of vegetable, mineral, or animal origin that neutralize free radicals and protect the body from their negative actions on the plasma membrane, proteins, and DNA. Hence, cancer can be prevented by the stimulation of the immune system to destroy cancer cells or to block their proliferation. Since living organisms may be studied as a whole complex system by the "omics sciences" which tend toward understanding and describing the global information of genes, mRNA, proteins, and metabolites, our aim is to use bioinformatics and systems biology to study cytokinome, which plays an important role in the evolution of inflammatory processes and is also a key component in the evolution of cancer, a disease recognized as depending on chronic inflammation and also with the concomitant presence of type 2 diabetes and obesity. On the whole, we define cytokinome as the totality of these proteins and their interactions in and around biological cells. Understanding the complex interaction network of cytokines in patients affected by cancers should be very useful both to follow the evolution of cancer from its early stages and to define innovative therapeutic strategies by using systems biology approaches. In this paper, we review some results of our group in the light of the "omics" logic, and in particular (1) the need for a global approach to study complex systems such as multifactorial cancer and, in particular, hepatocellular carcinoma, (2) the correlation between

Pre-Operative Prediction of Advanced Prostatic Cancer Using Clinical Decision Support Systems: Accuracy Comparison between Support Vector Machine and Artificial Neural Network

Energy Technology Data Exchange (ETDEWEB)

Kim, Sang Youn; Moon, Sung Kyoung; Hwang, Sung Il; Sung, Chang Kyu; Cho, Jeong Yeon; Kim, Seung Hyup; Lee, Hak Jong [Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Dae Chul [National Cancer Center, Ilsan (Korea, Republic of); Lee, Ji Won [Kangwon National University College of Medicine, Chuncheon (Korea, Republic of)

2011-10-15

The purpose of the current study was to develop support vector machine (SVM) and artificial neural network (ANN) models for the pre-operative prediction of advanced prostate cancer by using the parameters acquired from transrectal ultrasound (TRUS)-guided prostate biopsies, and to compare the accuracies between the two models. Five hundred thirty-two consecutive patients who underwent prostate biopsies and prostatectomies for prostate cancer were divided into the training and test groups (n = 300 versus n 232). From the data in the training group, two clinical decision support systems (CDSSs-[SVM and ANN]) were constructed with input (age, prostate specific antigen level, digital rectal examination, and five biopsy parameters) and output data (the probability for advanced prostate cancer [> pT3a]). From the data of the test group, the accuracy of output data was evaluated. The areas under the receiver operating characteristic (ROC) curve (AUC) were calculated to summarize the overall performances, and a comparison of the ROC curves was performed (p < 0.05). The AUC of SVM and ANN is 0.805 and 0.719, respectively (p = 0.020), in the pre-operative prediction of advanced prostate cancer. Te performance of SVM is superior to ANN in the pre-operative prediction of advanced prostate cancer.

Noise Analysis studies with neural networks

International Nuclear Information System (INIS)

Seker, S.; Ciftcioglu, O.

1996-01-01

Noise analysis studies with neural network are aimed. Stochastic signals at the input of the network are used to obtain an algorithmic multivariate stochastic signal modeling. To this end, lattice modeling of a stochastic signal is performed to obtain backward residual noise sources which are uncorrelated among themselves. There are applied together with an additional input to the network to obtain an algorithmic model which is used for signal detection for early failure in plant monitoring. The additional input provides the information to the network to minimize the difference between the signal and the network's one-step-ahead prediction. A stochastic algorithm is used for training where the errors reflecting the measurement error during the training are also modelled so that fast and consistent convergence of network's weights is obtained. The lattice structure coupled to neural network investigated with measured signals from an actual power plant. (authors)

Studies on retrospective analysis of leading primary cancers and improvement of cancer treatment method in Korea cancer center hospital

Energy Technology Data Exchange (ETDEWEB)

Lee, Jong In; Lee, Kang Hyun; Choi, Soo Yong; Kim, Ki Wha; Kang, Sung Mok

2000-12-01

a. Retrospective studies included cancers of the stomach, breast, bladder, salivary gland, thyroid, esophagus, endometrium and ovary. (1) Study cancers were analyzed about clinical characteristics, prognostic factors influenced on survival time, survival rate, etc. (2) Among 5,305 study patients, 1,405(26.5%) were identified with death, 3,485(65.7%) were alive and 415(7.8%) were not identified. b. Prospective studies included 10 subjects such as bladder cancer, retinoblastoma, malignant patients, gastric cancer, uterine cervix cancer and ovary cancer. We are continuing registering eligible study patients. c. Results for 11 papers were published at the journal. d. We established follow-up system in order to identify the survival for study subjects through National Statistical Office, Government Provincial Office and Cancer Registration System at Korea Cancer Center Hospital. e. At present, we are establishing computerized registration system about case report form for study cancers.

Studies on retrospective analysis of leading primary cancers and improvement of cancer treatment method in Korea cancer center hospital

International Nuclear Information System (INIS)

Lee, Jong In; Lee, Kang Hyun; Choi, Soo Yong; Kim, Ki Wha; Kang, Sung Mok

2000-12-01

a. Retrospective studies included cancers of the stomach, breast, bladder, salivary gland, thyroid, esophagus, endometrium and ovary. (1) Study cancers were analyzed about clinical characteristics, prognostic factors influenced on survival time, survival rate, etc. (2) Among 5,305 study patients, 1,405(26.5%) were identified with death, 3,485(65.7%) were alive and 415(7.8%) were not identified. b. Prospective studies included 10 subjects such as bladder cancer, retinoblastoma, malignant patients, gastric cancer, uterine cervix cancer and ovary cancer. We are continuing registering eligible study patients. c. Results for 11 papers were published at the journal. d. We established follow-up system in order to identify the survival for study subjects through National Statistical Office, Government Provincial Office and Cancer Registration System at Korea Cancer Center Hospital. e. At present, we are establishing computerized registration system about case report form for study cancers

Scoping Study: Networked Microgrids.

Energy Technology Data Exchange (ETDEWEB)

Trinklei, Eddy; Parker, Gordon; Weaver, Wayne; Robinett, Rush; Babe Gauchia, Lucia; Ten, Chee-Wooi; Bower, Ward; Glover, Steven F.; Bukowski, Steve

2014-10-01

This report presents a scoping study for networked microgrids which are defined as "Interoperable groups of multiple Advanced Microgrids that become an integral part of the electricity grid while providing enhanced resiliency through self-healing, aggregated ancillary services, and real-time communication." They result in optimal electrical system configurations and controls whether grid-connected or in islanded modes and enable high penetrations of distributed and renewable energy resources. The vision for the purpose of this document is: "Networked microgrids seamlessly integrate with the electricity grid or other Electric Power Sources (EPS) providing cost effective, high quality, reliable, resilient, self-healing power delivery systems." Scoping Study: Networked Microgrids September 4, 2014 Eddy Trinklein, Michigan Technological University Gordon Parker, Michigan Technological University Wayne Weaver, Michigan Technological University Rush Robinett, Michigan Technological University Lucia Gauchia Babe, Michigan Technological University Chee-Wooi Ten, Michigan Technological University Ward Bower, Ward Bower Innovations LLC Steve Glover, Sandia National Laboratories Steve Bukowski, Sandia National Laboratories Prepared by Michigan Technological University Houghton, Michigan 49931 Michigan Technological University

Evaluation of exposure to pioglitazone and risk of prostate cancer: a nested case–control study

Science.gov (United States)

Boxall, Naomi; Bennett, Dimitri; Hunger, Matthias; Dolin, Paul; Thompson, Paula L

2016-01-01

Objectives Investigate potential association between pioglitazone exposure and risk of prostate cancer. Research design and methods Nested, matched case–control study. UK primary care data (Clinical Practice Research Datalink (CPRD) GOLD) linked to inpatient (Hospital Episode Statistics (HES)) and cancer registry (National Cancer Information Network (NCIN)) data. English men aged ≥40 years diagnosed with type 2 diabetes mellitus, January 1, 2001 to January 5, 2015. Cases, with prostate cancer diagnosis, matched with up to 4 controls by age, cohort entry date and region. ORs for association of exposure to pioglitazone to incident prostate cancer, adjusted for potential confounders. Results From a cohort of 47 772 men with 243 923 person-years follow-up, 756 definite cases of prostate cancer were identified. Incidence was 309.9/100 000 person-years (95% CI 288.6 to 332.8). Pioglitazone use was not associated with prostate cancer risk; adjusted OR 0.759, 95% CI 0.502 to 1.148. Analyses showed no difference when possible cases, prostate cancer in CPRD GOLD only, included (adjusted OR 0.726, 95% CI 0.510 to 1.034). No association when adjusted for channeling bias (OR 0.778, 95% CI 0.511 to 1.184) or limited to an index date prior to July 1, 2011 (adjusted OR 0.508, 95% CI 0.294 to 0.879), despite prostate-specific antigen screening occurring more frequently among cases than controls (81.6% of 756 definite cases cf. 24.2% of 2942 controls (pworld, nested matched case–control study, exposure to pioglitazone was not associated with increased risk of prostate cancer. PMID:28074141

Redes En Acción. Increasing Hispanic participation in cancer research, training, and awareness.

Science.gov (United States)

Ramirez, Amelie G; Talavera, Gregory A; Marti, Jose; Penedo, Frank J; Medrano, Martha A; Giachello, Aida L; Pérez-Stable, Eliseo J

2006-10-15

Hispanics are affected by many health care disparities. The National Cancer Institute (NCI), through its Special Populations Branch, is supporting networking and capacity-building activities designed to increase Hispanic participation and leadership in cancer research. Redes En Acción established a national network of cancer research centers, community-based organizations, and federal partners to facilitate opportunities for junior Hispanic scientists to participate in training and research projects on cancer control. Since 2000, Redes En Acción has established a network of more than 1800 Hispanic leaders involved in cancer research and education. The project has sustained 131 training positions and submitted 29 pilot projects to NCI for review, with 16 awards for a total of $800,000, plus an additional $8.8 million in competing grant funding based on pilot study results to date. Independent research has leveraged an additional $32 million in non-Redes funding, and together the national and regional network sites have participated in more than 1400 community and professional awareness events. In addition, the program conducted extensive national survey research that provided the basis for the Redes En Acción Latino Cancer Report, a national agenda on Hispanic cancer issues. Redes En Acción has increased participation in cancer control research, training, and awareness among Hispanic scientists and within Hispanic communities. Cancer 2006. (c) 2006 American Cancer Society.

A systematic atlas of chaperome deregulation topologies across the human cancer landscape

Science.gov (United States)

Sverchkova, Angelina

2018-01-01

Proteome balance is safeguarded by the proteostasis network (PN), an intricately regulated network of conserved processes that evolved to maintain native function of the diverse ensemble of protein species, ensuring cellular and organismal health. Proteostasis imbalances and collapse are implicated in a spectrum of human diseases, from neurodegeneration to cancer. The characteristics of PN disease alterations however have not been assessed in a systematic way. Since the chaperome is among the central components of the PN, we focused on the chaperome in our study by utilizing a curated functional ontology of the human chaperome that we connect in a high-confidence physical protein-protein interaction network. Challenged by the lack of a systems-level understanding of proteostasis alterations in the heterogeneous spectrum of human cancers, we assessed gene expression across more than 10,000 patient biopsies covering 22 solid cancers. We derived a novel customized Meta-PCA dimension reduction approach yielding M-scores as quantitative indicators of disease expression changes to condense the complexity of cancer transcriptomics datasets into quantitative functional network topographies. We confirm upregulation of the HSP90 family and also highlight HSP60s, Prefoldins, HSP100s, ER- and mitochondria-specific chaperones as pan-cancer enriched. Our analysis also reveals a surprisingly consistent strong downregulation of small heat shock proteins (sHSPs) and we stratify two cancer groups based on the preferential upregulation of ATP-dependent chaperones. Strikingly, our analyses highlight similarities between stem cell and cancer proteostasis, and diametrically opposed chaperome deregulation between cancers and neurodegenerative diseases. We developed a web-based Proteostasis Profiler tool (Pro2) enabling intuitive analysis and visual exploration of proteostasis disease alterations using gene expression data. Our study showcases a comprehensive profiling of chaperome shifts

A systematic atlas of chaperome deregulation topologies across the human cancer landscape.

Directory of Open Access Journals (Sweden)

Ali Hadizadeh Esfahani

2018-01-01

Full Text Available Proteome balance is safeguarded by the proteostasis network (PN, an intricately regulated network of conserved processes that evolved to maintain native function of the diverse ensemble of protein species, ensuring cellular and organismal health. Proteostasis imbalances and collapse are implicated in a spectrum of human diseases, from neurodegeneration to cancer. The characteristics of PN disease alterations however have not been assessed in a systematic way. Since the chaperome is among the central components of the PN, we focused on the chaperome in our study by utilizing a curated functional ontology of the human chaperome that we connect in a high-confidence physical protein-protein interaction network. Challenged by the lack of a systems-level understanding of proteostasis alterations in the heterogeneous spectrum of human cancers, we assessed gene expression across more than 10,000 patient biopsies covering 22 solid cancers. We derived a novel customized Meta-PCA dimension reduction approach yielding M-scores as quantitative indicators of disease expression changes to condense the complexity of cancer transcriptomics datasets into quantitative functional network topographies. We confirm upregulation of the HSP90 family and also highlight HSP60s, Prefoldins, HSP100s, ER- and mitochondria-specific chaperones as pan-cancer enriched. Our analysis also reveals a surprisingly consistent strong downregulation of small heat shock proteins (sHSPs and we stratify two cancer groups based on the preferential upregulation of ATP-dependent chaperones. Strikingly, our analyses highlight similarities between stem cell and cancer proteostasis, and diametrically opposed chaperome deregulation between cancers and neurodegenerative diseases. We developed a web-based Proteostasis Profiler tool (Pro2 enabling intuitive analysis and visual exploration of proteostasis disease alterations using gene expression data. Our study showcases a comprehensive profiling of

Cancer Support Needs for African American Breast Cancer Survivors and Caregivers.

Science.gov (United States)

Haynes-Maslow, Lindsey; Allicock, Marlyn; Johnson, La-Shell

2016-03-01

Improved cancer screening and treatment advances have led to higher cancer survival rates in the United States. However, racial disparities in breast cancer survival persist for African American women who experience lower survival rates than white women. These disparities suggest that unmet needs related to survivorship still exist. This study focuses on the challenges that both African American cancer survivors and caregivers face across the cancer continuum. Five African American focus groups examined cancer survivor and caregiver support needs. Focus groups were recorded, transcribed, and uploaded into Atlas.ti. Thematic content analysis was applied to the text during the coding process. Themes were identified and emphasized based on the research team's integrated and unified final codes. Forty-one African Americans participated in five focus groups: 22 cancer survivors and 19 caregivers. Participants discussed five themes: (1) a culture that discourages the discussion of cancer; (2) lack of support services for African American cancer survivors; (3) lack of support services for cancer caregivers; (4) need for culturally appropriate cancer resources, including resources targeted at African American women; and (5) aspects that were helpful to cancer survivors and caregivers, including connecting with other survivors and caregivers, and having strong social support networks. We gained new insight into the unmet support needs for survivors and caregivers, especially when coping with the cancer experience continuum. While some cancer and caregiver support services exist, our study reveals a great need for services that incorporate the cultural differences that exist across races.

Expanding Local Cancer Clinical Trial Options: Analysis of the Economic Impact of the Midwest Cancer Alliance in Kansas.

Science.gov (United States)

Gafford, J Atlee; Gurley-Calvez, Tami; Krebill, Hope; Lai, Sue Min; Christiadi; Doolittle, Gary C

2017-09-01

Patients benefit from receiving cancer treatment closer to home when possible and at high-volume regional centers when specialized care is required. The purpose of this analysis was to estimate the economic impact of retaining more patients in-state for cancer clinical trials and care, which might offset some of the costs of establishing broader cancer trial and treatment networks. Kansas Cancer Registry data were used to estimate the number of patients retained in-state for cancer care following the expansion of local cancer clinical trial options through the Midwest Cancer Alliance based at the University of Kansas Medical Center. The 2014 economic impact of this enhanced local clinical trial network was estimated in four parts: Medical spending was estimated on the basis of National Cancer Institute cost-of-care estimates. Household travel cost savings were estimated as the difference between in-state and out-of-state travel costs. Trial-related grant income was calculated from administrative records. Indirect and induced economic benefits to the state were estimated using an economic impact model. The authors estimated that the enhanced local cancer clinical trial network resulted in approximately $6.9 million in additional economic activity in the state in 2014, or $362,000 per patient retained in-state. This estimate includes $3.6 million in direct spending and $3.3 million in indirect economic activity. The enhanced trial network also resulted in 45 additional jobs. Retaining patients in-state for cancer care and clinical trial participation allows patients to remain closer to home for care and enhances the state economy.

Integrative Analysis of Subcellular Quantitative Proteomics Studies Reveals Functional Cytoskeleton Membrane-Lipid Raft Interactions in Cancer.

Science.gov (United States)

Shah, Anup D; Inder, Kerry L; Shah, Alok K; Cristino, Alexandre S; McKie, Arthur B; Gabra, Hani; Davis, Melissa J; Hill, Michelle M

2016-10-07

Lipid rafts are dynamic membrane microdomains that orchestrate molecular interactions and are implicated in cancer development. To understand the functions of lipid rafts in cancer, we performed an integrated analysis of quantitative lipid raft proteomics data sets modeling progression in breast cancer, melanoma, and renal cell carcinoma. This analysis revealed that cancer development is associated with increased membrane raft-cytoskeleton interactions, with ∼40% of elevated lipid raft proteins being cytoskeletal components. Previous studies suggest a potential functional role for the raft-cytoskeleton in the action of the putative tumor suppressors PTRF/Cavin-1 and Merlin. To extend the observation, we examined lipid raft proteome modulation by an unrelated tumor suppressor opioid binding protein cell-adhesion molecule (OPCML) in ovarian cancer SKOV3 cells. In agreement with the other model systems, quantitative proteomics revealed that 39% of OPCML-depleted lipid raft proteins are cytoskeletal components, with microfilaments and intermediate filaments specifically down-regulated. Furthermore, protein-protein interaction network and simulation analysis showed significantly higher interactions among cancer raft proteins compared with general human raft proteins. Collectively, these results suggest increased cytoskeleton-mediated stabilization of lipid raft domains with greater molecular interactions as a common, functional, and reversible feature of cancer cells.

Cancer risk at low doses of ionizing radiation. Artificial neural networks inference from atomic bomb survivors

International Nuclear Information System (INIS)

Sasaki, Masao S.; Tachibana, Akira; Takeda, Shunichi

2014-01-01

Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (1) the presence of a threshold that varied with organ, gender and age at exposure, and (2) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to 239 Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation–environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking. (author)

Province wide clinical governance network for clinical audit for quality improvement in endometrial cancer management.

Science.gov (United States)

Mandato, Vincenzo Dario; Formisano, Debora; Pirillo, Debora; Ciarlini, Gino; Cerami, Lillo Bruno; Ventura, Alessandro; Spreafico, Lorenzo; Palmieri, Tamara; La Sala, Giovanni Battista; Abrate, Martino

2012-01-01

According to the hub-and-spoke model introduced in the Provincial Healthcare System of Reggio Emilia, early endometrial cancer is treated in peripheral low-volume hospitals (spokes) by general gynecologist, whereas more complex cancers are treated by gynecological oncologists at the main hospital (hub). To guarantee a uniformly high standard of care to all patients with endometrial cancer treated in hub and spoke hospitals of Reggio Emilia Province. The specialists of the 5 hospitals of Reggio Emilia Province instituted an inter hospital and multidisciplinary oncology group to write common and shared guidelines based on evidence-based medicine through the use of clinical audit. They valued the process indicators before and after guidelines introduction identifying the site of improvement and verifying the standard achievement. Diagnostic hysteroscopy use increased significantly from preguideline period, 53%, to postguideline period, 74%. Magnetic resonance use and accuracy increased significantly from preguideline to postguideline periods: 8.1% to 35.3% and 37.3% to 74.7%, respectively. Laparoscopy use increased from 1.6% (preguideline) to 18.6 (postguideline). Early surgical complications decreased from 16% (preguideline) to 9% (postguideline). Radiotherapy use increased from 14.% (preguideline) to 32.3% (postguideline). It is possible for a provincial oncology group to build an oncology network providing an improvement in the assistance of patients with endometrial cancer through the use of clinical audit. Clinical audit made it possible to obtain the full attendance of specialists of various disciplines involved in the treatment of endometrial cancer to optimize response time schematizing process.

Do governance choices matter in health care networks?: an exploratory configuration study of health care networks

Science.gov (United States)

2013-01-01

Background Health care networks are widely used and accepted as an organizational form that enables integrated care as well as dealing with complex matters in health care. However, research on the governance of health care networks lags behind. The research aim of our study is to explore the type and importance of governance structure and governance mechanisms for network effectiveness. Methods The study has a multiple case study design and covers 22 health care networks. Using a configuration view, combinations of network governance and other network characteristics were studied on the level of the network. Based on interview and questionnaire data, network characteristics were identified and patterns in the data looked for. Results Neither a dominant (or optimal) governance structure or mechanism nor a perfect fit among governance and other characteristics were revealed, but a number of characteristics that need further study might be related to effective networks such as the role of governmental agencies, legitimacy, and relational, hierarchical, and contractual governance mechanisms as complementary factors. Conclusions Although the results emphasize the situational character of network governance and effectiveness, they give practitioners in the health care sector indications of which factors might be more or less crucial for network effectiveness. PMID:23800334

Cross-cancer genome-wide analysis of lung, ovary, breast, prostate and colorectal cancer reveals novel pleiotropic associations

Science.gov (United States)

Fehringer, Gordon; Kraft, Peter; Pharoah, Paul D.; Eeles, Rosalind A.; Chatterjee, Nilanjan; Schumacher, Fred; Schildkraut, Joellen; Lindström, Sara; Brennan, Paul; Bickeböller, Heike; Houlston, Richard S.; Landi, Maria Teresa; Caporaso, Neil; Risch, Angela; Olama, Ali Amin Al; Berndt, Sonja I; Giovannucci, Edward; Grönberg, Henrik; Kote-Jarai, Zsofia; Ma, Jing; Muir, Kenneth; Stampfer, Meir; Stevens, Victoria L.; Wiklund, Fredrik; Willett, Walter; Goode, Ellen L.; Permuth, Jennifer; Risch, Harvey A.; Reid, Brett M.; Bezieau, Stephane; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Hudson, Thomas J.; Kocarnik, Jonathan K.; Newcomb, Polly A.; Schoen, Robert E.; Slattery, Martha L.; White, Emily; Adank, Muriel A.; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Blomquist, Carl; Canzian, Federico; Czene, Kamila; dos-Santos-Silva, Isabel; Eliassen, A. Heather; Figueroa, Jonine; Flesch-Janys, Dieter; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Johnson, Nichola; Hall, Per; Hazra, Aditi; Hein, Rebecca; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sanchez, Maria Jose; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth C.; Turnbull, Clare; Uitterlinden, Andre G.; Wang, Zhaoming; Whittemore, Alice S.; Yang, Xiaohong R.; Zheng, Wei; Rafnar, Thorunn; Gudmundsson, Julius; Stacey, Simon N.; Stefansson, Kari; Sulem, Patrick; Chen, Y. Ann; Tyrer, Jonathan P.; Christiani, David C.; Wei, Yongyue; Shen, Hongbing; Hu, Zhibin; Shu, Xiao-Ou; Shiraishi, Kouya; Takahashi, Atsushi; Bossé, Yohan; Obeidat, Ma’en; Nickle, David; Timens, Wim; Freedman, Matthew L.; Li, Qiyuan; Seminara, Daniela; Chanock, Stephen J.; Gong, Jian; Peters, Ulrike; Gruber, Stephen B.; Amos, Christopher I.; Sellers, Thomas A.; Easton, Douglas F.; Hunter, David J.; Haiman, Christopher A.; Henderson, Brian E.; Hung, Rayjean J.

2016-01-01

Identifying genetic variants with pleiotropic associations can uncover common pathways influencing multiple cancers. We took a two-staged approach to conduct genome-wide association studies for lung, ovary, breast, prostate and colorectal cancer from the GAME-ON/GECCO Network (61,851 cases, 61,820 controls) to identify pleiotropic loci. Findings were replicated in independent association studies (55,789 cases, 330,490 controls). We identified a novel pleiotropic association at 1q22 involving breast and lung squamous cell carcinoma, with eQTL analysis showing an association with ADAM15/THBS3 gene expression in lung. We also identified a known breast cancer locus CASP8/ALS2CR12 associated with prostate cancer, a known cancer locus at CDKN2B-AS1 with different variants associated with lung adenocarcinoma and prostate cancer and confirmed the associations of a breast BRCA2 locus with lung and serous ovarian cancer. This is the largest study to date examining pleiotropy across multiple cancer-associated loci, identifying common mechanisms of cancer development and progression. PMID:27197191

Oral cancer: A multicenter study.

Science.gov (United States)

Dhanuthai, K; Rojanawatsirivej, S; Thosaporn, W; Kintarak, S; Subarnbhesaj, A; Darling, M; Kryshtalskyj, E; Chiang, C-P; Shin, H-I; Choi, S-Y; Lee, S-S; Aminishakib, P

2018-01-01

To determine the prevalence and clinicopathologic features of the oral cancer patients. Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as between Asian and non-Asian oral cancer patients.

Novel Holistic Approaches for Overcoming Therapy Resistance in Pancreatic and Colon Cancers.

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Sarkar, Fazlul H

2016-01-01

Gastrointestinal (GI) cancers, such as of the colon and pancreas, are highly resistant to both standard and targeted therapeutics. Therapy-resistant and heterogeneous GI cancers harbor highly complex signaling networks (the resistome) that resist apoptotic programming. Commonly used gemcitabine or platinum-based regimens fail to induce meaningful (i.e. disease-reversing) perturbations in the resistome, resulting in high rates of treatment failure. The GI cancer resistance networks are, in part, due to interactions between parallel signaling and aberrantly expressed microRNAs (miRNAs) that collectively promote the development and survival of drug-resistant cancer stem cells with epithelial-to-mesenchymal transition (EMT) characteristics. The lack of understanding of the resistance networks associated with this subpopulation of cells as well as reductionist, single protein-/pathway-targeted approaches have made 'effective drug design' a difficult task. We propose that the successful design of novel therapeutic regimens to target drug-resistant GI tumors is only possible if network-based drug avenues and agents, in particular 'natural agents' with no known toxicity, are correctly identified. Natural agents (dietary agents or their synthetic derivatives) can individually alter miRNA profiles, suppress EMT pathways and eliminate cancer stem-like cells that derive from pancreatic cancer and colon cancer, by partially targeting multiple yet meaningful networks within the GI cancer resistome. However, the efficacy of these agents as combinations (e.g. consumed in the diet) against this resistome has never been studied. This short review article provides an overview of the different challenges involved in the understanding of the GI resistome, and how novel computational biology can help in the design of effective therapies to overcome resistance. © 2015 S. Karger AG, Basel.

Analyzing collaboration networks and developmental patterns of nano-enabled drug delivery (NEDD for brain cancer

Directory of Open Access Journals (Sweden)

Ying Huang

2015-07-01

Full Text Available The rapid development of new and emerging science & technologies (NESTs brings unprecedented challenges, but also opportunities. In this paper, we use bibliometric and social network analyses, at country, institution, and individual levels, to explore the patterns of scientific networking for a key nano area – nano-enabled drug delivery (NEDD. NEDD has successfully been used clinically to modulate drug release and to target particular diseased tissues. The data for this research come from a global compilation of research publication information on NEDD directed at brain cancer. We derive a family of indicators that address multiple facets of research collaboration and knowledge transfer patterns. Results show that: (1 international cooperation is increasing, but networking characteristics change over time; (2 highly productive institutions also lead in influence, as measured by citation to their work, with American institutes leading; (3 research collaboration is dominated by local relationships, with interesting information available from authorship patterns that go well beyond journal impact factors. Results offer useful technical intelligence to help researchers identify potential collaborators and to help inform R&D management and science & innovation policy for such nanotechnologies.

Analysis of methylation profiling data of hyperplasia and primary and metastatic endometrial cancers.

Science.gov (United States)

Wu, Xihai; Miao, Jilan; Jiang, Jingyan; Liu, Fangmei

2017-10-01

Endometrial cancer is a prevalent cancer, and its metastasis causes low survival rate. This study aims to utilize DNA methylation data to investigate the mechanism of the development and metastasis of endometrial cancer. Methylation profiling data were down-loaded from Gene Expression Omnibus, including 8 hyperplasias, 33 primary and 53 metastatic endometrial cancers. COHCAP package and annotation files were utilized to identify differentially methylated genes (DMGs) and CpG islands between the three different endometrial diseases. STRING database and Cytoscape were used to analyze and visualize protein-protein interactions (PPIs) between DMGs. CytoNCA plugin was utilized to identify key nodes in PPI network. A total of 610, 1076, and 501 DMGs were identified between primary endometrial cancer and hyperplasia, metastatic endometrial cancer and hyperplasia, as well as metastatic and primary endometrial cancers, respectively. For the three DMG sets, 53 common hypermethylated DMGs (e.g. PAX6 and INSR) and 6 common hypomethylated DMGs (e.g. PRDM8, KLHL14, and DUSP6) were found. For primary-hyperplasia DMG set and metastasis-hyperplasia DMG set, 527 common DMGs were found. For these common DMGs, a PPI network involving 692 PPIs was constructed. For DMGs between metastatic and primary endometrial cancers, a PPI network involving 673 PPIs was established, with PAX6 and INSR in the top 20 DMGs in both networks. PRDM8, KLHL14, and DUSP6 had hypomethylated CpG islands. DMGs comparison, PPI network analysis, and analysis of differentially methylated CpG islands indicated that PAX6, INSR, PRDM8, KLHL14, and DUSP6 might participate in the development and metastasis of endometrial cancer. Copyright © 2017. Published by Elsevier B.V.

Surrogate for oropharyngeal cancer HPV status in cancer database studies.