WorldWideScience

Sample records for cancer systems biology

  1. [Systems biology of cancer].

    Science.gov (United States)

    Barillot, Emmanuel; Calzone, Laurence; Zinovyev, Andrei

    2009-01-01

    Cancer Systems Biology is now accepted and recognized as a promising field both in biological and clinical research. It relies on a rigorous formalization of regulation networks into precise and unambiguous languages. It provides both detailed and modular views of the complex biological system of interest (which in cancer research is typically an interaction network governing essential cellular events such as proliferation, differentiation, cell death...) in order to facilitate the interpretation of molecular profiles of tumors. The translation of these networks into mathematical models allows prediction of the evolution of the system in time and under certain perturbations. As a result, it can not only propose specific target points for pharmaceutical purposes, but also anticipate the evolution of tumors as well as their classifications. These characteristics emphasize the important role of Systems Biology of Cancer in the future of biomedical research.

  2. Network systems biology for targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Zhou

    2012-01-01

    The era of targeted cancer therapies has arrived.However,due to the complexity of biological systems,the current progress is far from enough.From biological network modeling to structural/dynamic network analysis,network systems biology provides unique insight into the potential mechanisms underlying the growth and progression of cancer cells.It has also introduced great changes into the research paradigm of cancer-associated drug discovery and drug resistance.

  3. Systems biology and cancer, [Editorial

    OpenAIRE

    Soto, A M; Sonnenschein, C; Maini, P.K.

    2011-01-01

    The systems approach to complex biological problems has rapidly gained ground during the first decade of this century. There are several reasons for this development. An important one is that while the achievement of sequencing the complete human genome, and those of other species, has been of great benefit to fundamental science, for example in comparative genomics and evolutionary biology, it has not led to the expected quick and simple solutions to multifactorial diseases (2010). On the co...

  4. Systems biology of cancer biomarker detection.

    Science.gov (United States)

    Mitra, Sanga; Das, Smarajit; Chakrabarti, Jayprokas

    2013-01-01

    Cancer systems-biology is an ever-growing area of research due to explosion of data; how to mine these data and extract useful information is the problem. To have an insight on carcinogenesis one need to systematically mine several resources, such as databases, microarray and next-generation sequences. This review encompasses management and analysis of cancer data, databases construction and data deposition, whole transcriptome and genome comparison, analysing results from high throughput experiments to uncover cellular pathways and molecular interactions, and the design of effective algorithms to identify potential biomarkers. Recent technical advances such as ChIP-on-chip, ChIP-seq and RNA-seq can be applied to get epigenetic information transformed into a high-throughput endeavour to which systems biology and bioinformatics are making significant inroads. The data from ENCODE and GENCODE projects available through UCSC genome browser can be considered as benchmark for comparison and meta-analysis. A pipeline for integrating next generation sequencing data, microarray data, and putting them together with the existing database is discussed. The understanding of cancer genomics is changing the way we approach cancer diagnosis and treatment. To give a better understanding of utilizing available resources' we have chosen oral cancer to show how and what kind of analysis can be done. This review is a computational genomic primer that provides a bird's eye view of computational and bioinformatics' tools currently available to perform integrated genomic and system biology analyses of several carcinoma.

  5. Computational systems biology in cancer brain metastasis.

    Science.gov (United States)

    Peng, Huiming; Tan, Hua; Zhao, Weiling; Jin, Guangxu; Sharma, Sambad; Xing, Fei; Watabe, Kounosuke; Zhou, Xiaobo

    2016-01-01

    Brain metastases occur in 20-40% of patients with advanced malignancies. A better understanding of the mechanism of this disease will help us to identify novel therapeutic strategies. In this review, we will discuss the systems biology approaches used in this area, including bioinformatics and mathematical modeling. Bioinformatics has been used for identifying the molecular mechanisms driving brain metastasis and mathematical modeling methods for analyzing dynamics of a system and predicting optimal therapeutic strategies. We will illustrate the strategies, procedures, and computational techniques used for studying systems biology in cancer brain metastases. We will give examples on how to use a systems biology approach to analyze a complex disease. Some of the approaches used to identify relevant networks, pathways, and possibly biomarkers in metastasis will be reviewed into details. Finally, certain challenges and possible future directions in this area will also be discussed.

  6. Cancer systems biology: signal processing for cancer research

    Institute of Scientific and Technical Information of China (English)

    Olli Yli-Harja; Antti Ylip(a)(a); Matti Nykter; Wei Zhang

    2011-01-01

    In this editorial we introduce the research paradigms of signal processing in the era of systems biology. Signal processing is a field of science traditionally focused on modeling electronic and communications systems, but recently it has turned to biological applications with astounding results. The essence of signal processing is to describe the natural world by mathematical models and then, based on these models, develop efficient computational tools for solving engineering problems. Here, we underline, with examples, the endless possibilities which arise when the battle-hardened tools of engineering are applied to solve the problems that have tormented cancer researchers. Based on this approach, a new field has emerged, called cancer systems biology. Despite its short history, cancer systems biology has already produced several success stories tackling previously impracticable problems. Perhaps most importantly, it has been accepted as an integral part of the major endeavors of cancer research, such as analyzing the genomic and epigenomic data produced by The Cancer Genome Atlas (TCGA) project. Finally, we show that signal processing and cancer research, two fields that are seemingly distant from each other, have merged into a field that is indeed more than the sum of its parts.

  7. Cancer systems biology: signal processing for cancer research.

    Science.gov (United States)

    Yli-Harja, Olli; Ylipää, Antti; Nykter, Matti; Zhang, Wei

    2011-04-01

    In this editorial we introduce the research paradigms of signal processing in the era of systems biology. Signal processing is a field of science traditionally focused on modeling electronic and communications systems, but recently it has turned to biological applications with astounding results. The essence of signal processing is to describe the natural world by mathematical models and then, based on these models, develop efficient computational tools for solving engineering problems. Here, we underline, with examples, the endless possibilities which arise when the battle-hardened tools of engineering are applied to solve the problems that have tormented cancer researchers. Based on this approach, a new field has emerged, called cancer systems biology. Despite its short history, cancer systems biology has already produced several success stories tackling previously impracticable problems. Perhaps most importantly, it has been accepted as an integral part of the major endeavors of cancer research, such as analyzing the genomic and epigenomic data produced by The Cancer Genome Atlas (TCGA) project. Finally, we show that signal processing and cancer research, two fields that are seemingly distant from each other, have merged into a field that is indeed more than the sum of its parts.

  8. Systems biology in the frontier of cancer research:a report of the Second International Workshop of Cancer Systems Biology

    Institute of Scientific and Technical Information of China (English)

    Juan Cui; Yan-Chun Liang; Ying Xu

    2012-01-01

    The report summarizes the Second International Workshop of Cancer Systems Biology held on July 5-6,2012 in Changchun,China.The goal of the workshop was to bring together cancer researchers with different backgrounds to share their views about cancer and their experiences in fighting against cancer,and to gain new and systems-level understanding about cancer formation,progression,diagnosis,and treatment through exchanging ideas.

  9. Systems biology in the frontier of cancer research: a report of the Second International Workshop of Cancer Systems Biology

    OpenAIRE

    Ying Xu; Yan-Chun Liang; Juan Cui

    2012-01-01

    The report summarizes the Second International Workshop of Cancer Systems Biology held on July 5-6, 2012 in Changchun, China. The goal of the workshop was to bring together cancer researchers with different backgrounds to share their views about cancer and their experiences in fighting against cancer, and to gain new and systems-level understanding about cancer formation, progression, diagnosis, and treatment through exchanging ideas.

  10. RNA Systems Biology for Cancer: From Diagnosis to Therapy.

    Science.gov (United States)

    Amirkhah, Raheleh; Farazmand, Ali; Wolkenhauer, Olaf; Schmitz, Ulf

    2016-01-01

    It is due to the advances in high-throughput omics data generation that RNA species have re-entered the focus of biomedical research. International collaborate efforts, like the ENCODE and GENCODE projects, have spawned thousands of previously unknown functional non-coding RNAs (ncRNAs) with various but primarily regulatory roles. Many of these are linked to the emergence and progression of human diseases. In particular, interdisciplinary studies integrating bioinformatics, systems biology, and biotechnological approaches have successfully characterized the role of ncRNAs in different human cancers. These efforts led to the identification of a new tool-kit for cancer diagnosis, monitoring, and treatment, which is now starting to enter and impact on clinical practice. This chapter is to elaborate on the state of the art in RNA systems biology, including a review and perspective on clinical applications toward an integrative RNA systems medicine approach. The focus is on the role of ncRNAs in cancer.

  11. Integration of proteomics into systems biology of cancer

    OpenAIRE

    Hanash, S; Schliekelman, M.; Q. Zhang; Taguchi, A

    2012-01-01

    Deciphering the complexity and heterogeneity of cancer benefits from integration of proteomic level data into systems biology efforts. The opportunities available as a result of advances in proteomic technologies, the successes to date and the challenges involved in integrating diverse datasets are addressed in this review.

  12. Integration of proteomics into systems biology of cancer.

    Science.gov (United States)

    Hanash, S; Schliekelman, M; Zhang, Q; Taguchi, A

    2012-01-01

    Deciphering the complexity and heterogeneity of cancer, benefits from integration of proteomic level data into systems biology efforts. The opportunities available as a result of advances in proteomic technologies, the successes to date, and the challenges involved in integrating diverse datasets are addressed in this review.

  13. Mathematical and Statistical Modeling in Cancer Systems Biology

    Directory of Open Access Journals (Sweden)

    Rachael eHageman Blair

    2012-06-01

    Full Text Available Cancer is a major health problem with high mortality rates. In the post-genome era, investigators have access to massive amounts of rapidly accumulating high-throughput data in publicly available databases, some of which are exclusively devoted to housing Cancer data. However, data interpretation efforts have not kept pace with data collection, and gained knowledge is not necessarily translating into better diagnoses and treatments. A fundamental problem is to integrate and interpret data to further our understanding in Cancer Systems Biology. Viewing cancer as a network provides insights into the complex mechanisms underlying the disease. Mathematical and statistical models provide an avenue for cancer network modeling. In this article, we review two widely used modeling paradigms: deterministic metabolic models and statistical graphical models. The strength of these approaches lies in their flexibility and predictive power. Once a model has been validated, it can be used to make predictions and generate hypotheses. We describe a number of diverse applications to Cancer Biology, including, the system-wide effects of drug-treatments, disease prognosis, tumor classification, forecasting treatment outcomes, and survival predictions.

  14. Systems Biology of cancer: Moving toward the Integrative Study of the metabolic alterations in cancer cells.

    Directory of Open Access Journals (Sweden)

    Claudia Erika Hernández Patiño

    2013-01-01

    Full Text Available One of the main objectives in systems biology is to understand the biological mechanisms that give rise to the phenotype of a microorganism by using high-throughput technologies and genome-scale mathematical modeling. The computational modeling of genome-scale metabolic reconstructions is one systemic and quantitative strategy for characterizing the metabolic phenotype associated with human diseases and potentially for designing drugs with optimal clinical effects. The purpose of this short review is to describe how computational modeling, including the specific case of constraint-based modeling, can be used to explore, characterize and predict the metabolic capacities that distinguish the metabolic phenotype of cancer cell lines. As we show herein, this computational framework is far from a pure theoretical description, and to ensure proper biological interpretation, it is necessary to integrate high-throughput data and generate predictions for later experimental assessment. Hence, genome-scale modeling serves as a platform for the following: 1 the integration of data from high-throughput technologies, 2 the assessment of how metabolic activity is related to phenotype in cancer cell lines and 3 the design of new experiments to evaluate the outcomes of the in silico analysis. By combining the functions described above, we show that computational modeling is a useful methodology to construct an integrative, systemic and quantitative scheme for understanding the metabolic profiles of cancer cell lines, a first step to determine the metabolic mechanism by which cancer cells maintain and support their malignant phenotype in human tissues.

  15. Systems biology of cancer: moving toward the integrative study of the metabolic alterations in cancer cells.

    Science.gov (United States)

    Hernández Patiño, Claudia E; Jaime-Muñoz, Gustavo; Resendis-Antonio, Osbaldo

    2012-01-01

    One of the main objectives in systems biology is to understand the biological mechanisms that give rise to the phenotype of a microorganism by using high-throughput technologies (HTs) and genome-scale mathematical modeling. The computational modeling of genome-scale metabolic reconstructions is one systemic and quantitative strategy for characterizing the metabolic phenotype associated with human diseases and potentially for designing drugs with optimal clinical effects. The purpose of this short review is to describe how computational modeling, including the specific case of constraint-based modeling, can be used to explore, characterize, and predict the metabolic capacities that distinguish the metabolic phenotype of cancer cell lines. As we show herein, this computational framework is far from a pure theoretical description, and to ensure proper biological interpretation, it is necessary to integrate high-throughput data and generate predictions for later experimental assessment. Hence, genome-scale modeling serves as a platform for the following: (1) the integration of data from HTs, (2) the assessment of how metabolic activity is related to phenotype in cancer cell lines, and (3) the design of new experiments to evaluate the outcomes of the in silico analysis. By combining the functions described above, we show that computational modeling is a useful methodology to construct an integrative, systemic, and quantitative scheme for understanding the metabolic profiles of cancer cell lines, a first step to determine the metabolic mechanism by which cancer cells maintain and support their malignant phenotype in human tissues.

  16. Evolutionary biology of cancer.

    Science.gov (United States)

    Crespi, Bernard; Summers, Kyle

    2005-10-01

    Cancer is driven by the somatic evolution of cell lineages that have escaped controls on replication and by the population-level evolution of genes that influence cancer risk. We describe here how recent evolutionary ecological studies have elucidated the roles of predation by the immune system and competition among normal and cancerous cells in the somatic evolution of cancer. Recent analyses of the evolution of cancer at the population level show how rapid changes in human environments have augmented cancer risk, how strong selection has frequently led to increased cancer risk as a byproduct, and how anticancer selection has led to tumor-suppression systems, tissue designs that slow somatic evolution, constraints on morphological evolution and even senescence itself. We discuss how applications of the tools of ecology and evolutionary biology are poised to revolutionize our understanding and treatment of this disease.

  17. Computational systems biology approaches to anti-angiogenic cancer therapeutics.

    Science.gov (United States)

    Finley, Stacey D; Chu, Liang-Hui; Popel, Aleksander S

    2015-02-01

    Angiogenesis is an exquisitely regulated process that is required for physiological processes and is also important in numerous diseases. Tumors utilize angiogenesis to generate the vascular network needed to supply the cancer cells with nutrients and oxygen, and many cancer drugs aim to inhibit tumor angiogenesis. Anti-angiogenic therapy involves inhibiting multiple cell types, molecular targets, and intracellular signaling pathways. Computational tools are useful in guiding treatment strategies, predicting the response to treatment, and identifying new targets of interest. Here, we describe progress that has been made in applying mathematical modeling and bioinformatics approaches to study anti-angiogenic therapeutics in cancer.

  18. Systems Biology of Cancer: A Challenging Expedition for Clinical and Quantitative Biologists

    Directory of Open Access Journals (Sweden)

    Ilya eKorsunsky

    2014-08-01

    Full Text Available A systems-biology approach to complex disease (such as cancer is now complementing traditional experience-based approaches, which have typically been invasive and expensive. The rapid progress in biomedical knowledge is enabling the targeting of disease with therapies that are precise, proactive, preventive and personalized. In this paper, we summarize and classify models of systems biology and model-checking tools which have been used to great success in computational biology and related fields. We demonstrate how these models and tools have been used to study some of the twelve biochemical pathways implicated in but not unique to pancreatic cancer, and conclude that the resulting mechanistic models will need to be further enhanced by various abstraction techniques to interpret phenomenological models of cancer progression.

  19. Systems biology of cancer: a challenging expedition for clinical and quantitative biologists.

    Science.gov (United States)

    Korsunsky, Ilya; McGovern, Kathleen; LaGatta, Tom; Olde Loohuis, Loes; Grosso-Applewhite, Terri; Griffeth, Nancy; Mishra, Bud

    2014-01-01

    A systems-biology approach to complex disease (such as cancer) is now complementing traditional experience-based approaches, which have typically been invasive and expensive. The rapid progress in biomedical knowledge is enabling the targeting of disease with therapies that are precise, proactive, preventive, and personalized. In this paper, we summarize and classify models of systems biology and model checking tools, which have been used to great success in computational biology and related fields. We demonstrate how these models and tools have been used to study some of the twelve biochemical pathways implicated in but not unique to pancreatic cancer, and conclude that the resulting mechanistic models will need to be further enhanced by various abstraction techniques to interpret phenomenological models of cancer progression.

  20. Developing optimal input design strategies in cancer systems biology with applications to microfluidic device engineering

    OpenAIRE

    Maiwald Thomas; Bellomo Domenico; Menolascina Filippo; Bevilacqua Vitoantonio; Ciminelli Caterina; Paradiso Angelo; Tommasi Stefania

    2009-01-01

    Abstract Background Mechanistic models are becoming more and more popular in Systems Biology; identification and control of models underlying biochemical pathways of interest in oncology is a primary goal in this field. Unfortunately the scarce availability of data still limits our understanding of the intrinsic characteristics of complex pathologies like cancer: acquiring information for a system understanding of complex reaction networks is time consuming and expensive. Stimulus response ex...

  1. Atlas of Cancer Signalling Network: a systems biology resource for integrative analysis of cancer data with Google Maps.

    Science.gov (United States)

    Kuperstein, I; Bonnet, E; Nguyen, H-A; Cohen, D; Viara, E; Grieco, L; Fourquet, S; Calzone, L; Russo, C; Kondratova, M; Dutreix, M; Barillot, E; Zinovyev, A

    2015-01-01

    Cancerogenesis is driven by mutations leading to aberrant functioning of a complex network of molecular interactions and simultaneously affecting multiple cellular functions. Therefore, the successful application of bioinformatics and systems biology methods for analysis of high-throughput data in cancer research heavily depends on availability of global and detailed reconstructions of signalling networks amenable for computational analysis. We present here the Atlas of Cancer Signalling Network (ACSN), an interactive and comprehensive map of molecular mechanisms implicated in cancer. The resource includes tools for map navigation, visualization and analysis of molecular data in the context of signalling network maps. Constructing and updating ACSN involves careful manual curation of molecular biology literature and participation of experts in the corresponding fields. The cancer-oriented content of ACSN is completely original and covers major mechanisms involved in cancer progression, including DNA repair, cell survival, apoptosis, cell cycle, EMT and cell motility. Cell signalling mechanisms are depicted in detail, together creating a seamless 'geographic-like' map of molecular interactions frequently deregulated in cancer. The map is browsable using NaviCell web interface using the Google Maps engine and semantic zooming principle. The associated web-blog provides a forum for commenting and curating the ACSN content. ACSN allows uploading heterogeneous omics data from users on top of the maps for visualization and performing functional analyses. We suggest several scenarios for ACSN application in cancer research, particularly for visualizing high-throughput data, starting from small interfering RNA-based screening results or mutation frequencies to innovative ways of exploring transcriptomes and phosphoproteomes. Integration and analysis of these data in the context of ACSN may help interpret their biological significance and formulate mechanistic hypotheses

  2. Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a metabolic master regulator

    Directory of Open Access Journals (Sweden)

    Fabian V Filipp

    2013-01-01

    Full Text Available Pyruvate kinase activity is controlled by a tightly woven regulatory network. The oncofetal isoform of pyruvate kinase (PKM2 is a master regulator of cancer metabolism. PKM2 engages in parallel, feed-forward, positive and negative feedback control contributing to cancer progression. Besides its metabolic role, non-metabolic functions of PKM2 as protein kinase and transcriptional coactivator for c-MYC and hypoxia-inducible factor 1-alpha are essential for epidermal growth factor receptor activation-induced tumorigenesis. These biochemical activities are controlled by a shift in the oligomeric state of PKM2 that includes acetylation, oxidation, phosphorylation, prolyl hydroxylation and sumoylation. Metabolically active PKM2 tetramer is allosterically regulated and responds to nutritional and stress signals. Metabolically inactive PKM2 dimer is imported into the nucleus and can function as protein kinase stimulating transcription. A systems biology approach to PKM2 at the genome, transcriptome, proteome, metabolome and fluxome level reveals how differences in biomolecular structure translate into a global rewiring of cancer metabolism. Cancer systems biology takes us beyond the Warburg effect, opening unprecedented therapeutic opportunities.

  3. Relevance of the neuropeptide Y system in the biology of cancer progression.

    Science.gov (United States)

    Ruscica, M; Dozio, E; Motta, M; Magni, P

    2007-01-01

    The peptides pancreatic polypeptide (PP), peptide YY (PYY), and neuropeptide Y (NPY) share a similar structure, known as PP-fold. Within this family of peptides, NPY, a highly conserved 36-aminoacid residue peptide, is involved in the regulation of a wide range of physiological functions, such as food intake and energy metabolism, as well as in the promotion of some remarkable aspects of tumor progression, including cell proliferation, matrix invasion, metastatization, and angiogenesis. NPY exerts its biological effects through five G-protein coupled receptors, named Y1-, Y2-, Y4-, Y5-, and y6-R, which appear associated with different aspects of oncogenesis. Y1-R seems involved in the modulation of cancer cell proliferation, whereas Y2-R activation appears to promote angiogenesis. The development of NPY receptor subtype selective analogs has helped to elucidate the physiological and pathophysiological role and localization of each receptor and may contribute to a better understanding of the receptor-ligand interaction. The NPY system appears to be variously associated with specific tumors, including neural crest-derived tumors, breast and prostate cancers. In addition to NPY, PYY is also able to affect cancer cell growth in a dose-dependent manner and through Y-Rs. In conclusion, peptides of the NPY family and the related receptors play an important role in the progression of different cancer types, with some molecular specificity according to each step of this process. On this basis, future studies may be directed to the implementation of novel diagnostic and therapeutic approaches targeting this system.

  4. Biologic Therapy (Immunotherapy) for Kidney Cancer

    Science.gov (United States)

    ... for kidney cancer Targeted therapies for kidney cancer Biologic therapy (immunotherapy) for kidney cancer Chemotherapy for kidney cancer Pain control for kidney cancer Treatment choices by stage for ...

  5. Protocols for assessing radiofrequency interactions with gold nanoparticles and biological systems for non-invasive hyperthermia cancer therapy.

    Science.gov (United States)

    Corr, Stuart J; Cisneros, Brandon T; Green, Leila; Raoof, Mustafa; Curley, Steven A

    2013-08-28

    Cancer therapies which are less toxic and invasive than their existing counterparts are highly desirable. The use of RF electric-fields that penetrate deep into the body, causing minimal toxicity, are currently being studied as a viable means of non-invasive cancer therapy. It is envisioned that the interactions of RF energy with internalized nanoparticles (NPs) can liberate heat which can then cause overheating (hyperthermia) of the cell, ultimately ending in cell necrosis. In the case of non-biological systems, we present detailed protocols relating to quantifying the heat liberated by highly-concentrated NP colloids. For biological systems, in the case of in vitro experiments, we describe the techniques and conditions which must be adhered to in order to effectively expose cancer cells to RF energy without bulk media heating artifacts significantly obscuring the data. Finally, we give a detailed methodology for in vivo mouse models with ectopic hepatic cancer tumors.

  6. Biological Networks for Cancer Candidate Biomarkers Discovery

    Science.gov (United States)

    Yan, Wenying; Xue, Wenjin; Chen, Jiajia; Hu, Guang

    2016-01-01

    Due to its extraordinary heterogeneity and complexity, cancer is often proposed as a model case of a systems biology disease or network disease. There is a critical need of effective biomarkers for cancer diagnosis and/or outcome prediction from system level analyses. Methods based on integrating omics data into networks have the potential to revolutionize the identification of cancer biomarkers. Deciphering the biological networks underlying cancer is undoubtedly important for understanding the molecular mechanisms of the disease and identifying effective biomarkers. In this review, the networks constructed for cancer biomarker discovery based on different omics level data are described and illustrated from recent advances in the field.

  7. Biological Networks for Cancer Candidate Biomarkers Discovery.

    Science.gov (United States)

    Yan, Wenying; Xue, Wenjin; Chen, Jiajia; Hu, Guang

    2016-01-01

    Due to its extraordinary heterogeneity and complexity, cancer is often proposed as a model case of a systems biology disease or network disease. There is a critical need of effective biomarkers for cancer diagnosis and/or outcome prediction from system level analyses. Methods based on integrating omics data into networks have the potential to revolutionize the identification of cancer biomarkers. Deciphering the biological networks underlying cancer is undoubtedly important for understanding the molecular mechanisms of the disease and identifying effective biomarkers. In this review, the networks constructed for cancer biomarker discovery based on different omics level data are described and illustrated from recent advances in the field. PMID:27625573

  8. The role of CRKL in Breast Cancer Metastasis: Insights from Systems Biology

    OpenAIRE

    Chafik, Abderrahim

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally. They are involved in key biological processes and then may play a major role in the development of human diseases including cancer, in particular their involvement in breast cancer metastasis has been confirmed. Recently, the authors of ref.(\\cite{key1} have found that miR-429 may have a role in the inhibition of breast cancer metastasis and have identified its target gene CRKL as a potential ca...

  9. The Role of Model Integration in Complex Systems Modelling An Example from Cancer Biology

    CERN Document Server

    Patel, Manish

    2010-01-01

    Model integration – the process by which different modelling efforts can be brought together to simulate the target system – is a core technology in the field of Systems Biology. In the work presented here model integration was addressed directly taking cancer systems as an example. An in-depth literature review was carried out to survey the model forms and types currently being utilised. This was used to formalise the main challenges that model integration poses, namely that of paradigm (the formalism on which a model is based), focus (the real-world system the model represents) and scale. A two-tier model integration strategy, including a knowledge-driven approach to address model semantics, was developed to tackle these challenges. In the first step a novel description of models at the level of behaviour, rather than the precise mathematical or computational basis of the model, is developed by distilling a set of abstract classes and properties. These can accurately describe model behaviour and hence d...

  10. Prostate cancer stem cell biology

    OpenAIRE

    Yu, Chunyan; Yao, Zhi; Jiang, Yuan; Keller, Evan T.

    2012-01-01

    The cancer stem cell (CSC) model provides insights into pathophysiology of cancers and their therapeutic response. The CSC model has been both controversial, yet provides a foundation to explore cancer biology. In this review, we provide an overview of CSC concepts, biology and potential therapeutic avenues. We then focus on prostate CSC including (1) their purported origin as either basal-derived or luminal-derived cells; (2) markers used for prostate CSC identification; (3) alterations of s...

  11. Protein microarrays for systems biology

    Institute of Scientific and Technical Information of China (English)

    Lina Yang; Shujuan Guo; Yang Li; Shumin Zhou; Shengce Tao

    2011-01-01

    Systems biology holds the key for understanding biological systems on a system level. It eventually holds the key for the treatment and cure of complex diseases such as cancer,diabetes, obesity, mental disorders, and many others. The '-omics' technologies, such as genomics, transcriptomics,proteomics, and metabonomics, are among the major driving forces of systems biology. Featured as highthroughput, miniaturized, and capable of parallel analysis,protein microarrays have already become an important technology platform for systems biology, In this review, we will focus on the system level or global analysis of biological systems using protein microarrays. Four major types of protein microarrays will be discussed: proteome microarrays, antibody microarrays, reverse-phase protein arrays,and lectin microarrays. We will also discuss the challenges and future directions of protein microarray technologies and their applications for systems biology. We strongly believe that protein microarrays will soon become an indispensable and invaluable tool for systems biology.

  12. Systems biology reveals new strategies for personalizing cancer medicine and confirms the role of PTEN in resistance to trastuzumab.

    Science.gov (United States)

    Faratian, Dana; Goltsov, Alexey; Lebedeva, Galina; Sorokin, Anatoly; Moodie, Stuart; Mullen, Peter; Kay, Charlene; Um, In Hwa; Langdon, Simon; Goryanin, Igor; Harrison, David J

    2009-08-15

    Resistance to targeted cancer therapies such as trastuzumab is a frequent clinical problem not solely because of insufficient expression of HER2 receptor but also because of the overriding activation states of cell signaling pathways. Systems biology approaches lend themselves to rapid in silico testing of factors, which may confer resistance to targeted therapies. Inthis study, we aimed to develop a new kinetic model that could be interrogated to predict resistance to receptor tyrosine kinase (RTK) inhibitor therapies and directly test predictions in vitro and in clinical samples. The new mathematical model included RTK inhibitor antibody binding, HER2/HER3 dimerization and inhibition, AKT/mitogen-activated protein kinase cross-talk, and the regulatory properties of PTEN. The model was parameterized using quantitative phosphoprotein expression data from cancer cell lines using reverse-phase protein microarrays. Quantitative PTEN protein expression was found to be the key determinant of resistance to anti-HER2 therapy in silico, which was predictive of unseen experiments in vitro using the PTEN inhibitor bp(V). When measured in cancer cell lines, PTEN expression predicts sensitivity to anti-HER2 therapy; furthermore, this quantitative measurement is more predictive of response (relative risk, 3.0; 95% confidence interval, 1.6-5.5; P biology approach has successfully been used to stratify patients for personalized therapy in cancer and is further compelling evidence that PTEN, appropriately measured in the clinical setting, refines clinical decision making in patients treated with anti-HER2 therapies.

  13. Biological heterogeneity of cancer

    OpenAIRE

    Isaiah J. Fidler

    2012-01-01

    Despite significant improvements in diagnosis, surgical techniques, and advancements in general patient care, the majority of deaths from cancer are caused by the continuous growth of metastases that are resistant to conventional therapies. In a large number of cancer patients, metastasis may well have occurred by the time of diagnosis. The metastases can be located in different distant organs and in different regions within a single organ. The major obstacle for the eradication of metastases...

  14. Breast cancer biology for the radiation oncologist

    Energy Technology Data Exchange (ETDEWEB)

    Strauss, Jonathan [Northwestern Univ., Chicago, IL (United States). Dept. of Radiation Oncology; Small, William [Loyola Univ. Chicago, Maywood, IL (United States). Stritch School of Medicine, Cardianl Bernardin Cancer Center; Woloschak, Gayle E. (ed.) [Northwestern Univ. Feinberg, Chicago, IL (United States). School of Medicine

    2015-10-01

    This is the first textbook of its kind devoted to describing the biological complexities of breast cancer in a way that is relevant to the radiation oncologist. Radiation Oncology has long treated breast cancer as a single biological entity, with all treatment decisions being based on clinical and pathologic risk factors. We are now beginning to understand that biological subtypes of breast cancer may have different risks of recurrence as well as different intrinsic sensitivity to radiotherapy. Multi-gene arrays that have for years been used to predict the risk of distant recurrence and the value of systemic chemotherapy may also have utility in predicting the risk of local recurrence. Additionally, the targeted agents used to treat breast cancer may interact with radiotherapy in ways that can be beneficial or undesirable. All of these emerging issues are extensively discussed in this book, and practical evidence-based treatment recommendations are presented whenever possible.

  15. Computational Systems Chemical Biology

    OpenAIRE

    Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007).

  16. [Biology of cancer metastasis].

    Science.gov (United States)

    Robert, Jacques

    2013-04-01

    Metastatic dissemination represents the true cause of the malignant character of cancers. Its targeting is much more difficult than that of cell proliferation, because metastasis, like angiogenesis, involves a number of complex interactions between tumour and stroma; the contribution of adhesion and motility pathways is added to that of proliferation and survival pathways. Long distance extension, discontinuous in respect to the primitive tumour, is a major feature of cancer and the main cause of patients' death. Cancer cells use two main dissemination pathways: the lymphatic pathway, leading to the invasion of the lymph nodes draining the organs where the tumour evolves; and the blood pathway, leading to the invasion of distant organs such as liver, brain, bone or lung. Metastasis is inscribed within the properties of the primitive tumour, as shown by the comparative molecular analysis of the primitive tumour and its own metastases: their similarity is always more important than what could be expected from the general activation of "metastasis genes" or the inhibition of "metastasis suppressor genes". Among the signalling pathways involved in metastasis, one can mention the integrin pathway, the transforming growth factor beta (TGFβ) pathway, the chemokine pathway, the dependence receptor pathway and many others. These pathways allow the possibility of therapeutic targeting, thanks to therapeutic antibodies or small molecules inhibiting the kinases involved in these signalling pathways, but not a single properly anti-metastatic drug has yet been proposed: the complexity and the diversity of the processes allowing metastasis emergence, as well as the fact that the activation mechanisms are more often epigenetic than genetic and are generally physiological processes misled by the malignant cell, render especially difficult the therapeutic approach of metastasis.

  17. Integrative radiation systems biology.

    Science.gov (United States)

    Unger, Kristian

    2014-01-01

    Maximisation of the ratio of normal tissue preservation and tumour cell reduction is the main concept of radiotherapy alone or combined with chemo-, immuno- or biologically targeted therapy. The foremost parameter influencing this ratio is radiation sensitivity and its modulation towards a more efficient killing of tumour cells and a better preservation of normal tissue at the same time is the overall aim of modern therapy schemas. Nevertheless, this requires a deep understanding of the molecular mechanisms of radiation sensitivity in order to identify its key players as potential therapeutic targets. Moreover, the success of conventional approaches that tried to statistically associate altered radiation sensitivity with any molecular phenotype such as gene expression proofed to be somewhat limited since the number of clinically used targets is rather sparse. However, currently a paradigm shift is taking place from pure frequentistic association analysis to the rather holistic systems biology approach that seeks to mathematically model the system to be investigated and to allow the prediction of an altered phenotype as the function of one single or a signature of biomarkers. Integrative systems biology also considers the data from different molecular levels such as the genome, transcriptome or proteome in order to partially or fully comprehend the causal chain of molecular mechanisms. An example for the application of this concept currently carried out at the Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer" of the Helmholtz-Zentrum München and the LMU Munich is described. This review article strives for providing a compact overview on the state of the art of systems biology, its actual challenges, potential applications, chances and limitations in radiation oncology research working towards improved personalised therapy concepts using this relatively new methodology. PMID:24411063

  18. Progress in Systems Biological Modeling of Cancer%癌症的系统生物学模型研究进展

    Institute of Scientific and Technical Information of China (English)

    周建平

    2014-01-01

    Systems biology is a biology-based inter-disciplinary field which focuses on complex interactions within biological systems. Systems biological study can integrate multi-dimensional data describing the target biological system at different levels, and establish mathematical models of the system to study the characteristic behaviors of the system by virtual simulation, interference and forecasts. As complex biological systems, cancers have been extensively studied in systems biology. Systems biology models of cancers,including statistics-based models,signaling and metabolic bio-chemical models and tissue-level models,are valuable supplement to traditional animal models in cancer research. In this review, some valuable mathematical modeling efforts made in cancer systems biology were overviewed.%系统生物学研究采用的是系统性的研究方法,即获取并整合目标系统不同层次的生物学信息,构建适用于该生物系统的数学模型,对该系统的特征性行为进行系统性研究。癌症是一种复杂的生物系统,已成为系统生物学研究的热点领域。癌症的系统生物学模型是对传统的癌症动物模型的补充,主要包括:统计推断模型、生化网络模型、以及组织水平模型等。本文综述了这些系统模型方法在癌症研究中的应用情况及其取得的重要研究成果。

  19. Systems interface biology

    OpenAIRE

    Francis J Doyle; Stelling, Jörg

    2006-01-01

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Henc...

  20. Microbeam radiation therapy. Physical and biological aspects of a new cancer therapy and development of a treatment planning system

    Energy Technology Data Exchange (ETDEWEB)

    Bartzsch, Stefan

    2014-11-05

    Microbeam Radiation Therapy (MRT) is a novel treatment strategy against cancer. Highly brilliant synchrotron radiation is collimated to parallel, a few micrometre wide, planar beams and used to irradiate malignant tissues with high doses. The applied peak doses are considerably higher than in conventional radiotherapy, but valley doses between the beams remain underneath the established tissue tolerance. Previous research has shown that these beam geometries spare normal tissue, while being effective in tumour ablation. In this work physical and biological aspects of the therapy were investigated. A therapy planning system was developed for the first clinical treatments at the European Synchrotron Radiation Facility in Grenoble (France) and a dosimetry method based on radiochromic films was created to validate planned doses with measurements on a micrometre scale. Finally, experiments were carried out on a cellular level in order to correlate the physically planned doses with the biological damage caused in the tissue. The differences between Monte Carlo dose and dosimetry are less than 10% in the valley and 5% in the peak regions. Developed alternative faster dose calculation methods deviate from the computational intensive MC simulations by less than 15% and are able to determine the dose within a few minutes. The experiments in cell biology revealed an significant influence of intercellular signalling on the survival of cells close to radiation boundaries. These observations may not only be important for MRT but also for conventional radiotherapy.

  1. Systems biology of cancer: entropy, disorder, and selection-driven evolution to independence, invasion and "swarm intelligence".

    Science.gov (United States)

    Tarabichi, M; Antoniou, A; Saiselet, M; Pita, J M; Andry, G; Dumont, J E; Detours, V; Maenhaut, C

    2013-12-01

    Our knowledge of the biology of solid cancer has greatly progressed during the last few years, and many excellent reviews dealing with the various aspects of this biology have appeared. In the present review, we attempt to bring together these subjects in a general systems biology narrative. It starts from the roles of what we term entropy of signaling and noise in the initial oncogenic events, to the first major transition of tumorigenesis: the independence of the tumor cell and the switch in its physiology, i.e., from subservience to the organism to its own independent Darwinian evolution. The development after independence involves a constant dynamic reprogramming of the cells and the emergence of a sort of collective intelligence leading to invasion and metastasis and seldom to the ultimate acquisition of immortality through inter-individual infection. At each step, the probability of success is minimal to infinitesimal, but the number of cells possibly involved and the time scale account for the relatively high occurrence of tumorigenesis and metastasis in multicellular organisms.

  2. Computational systems chemical biology.

    Science.gov (United States)

    Oprea, Tudor I; May, Elebeoba E; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology (SCB) (Nat Chem Biol 3: 447-450, 2007).The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules, and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology/systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology, and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology.

  3. Advancing Cancer Systems Biology: Introducing the Center for the Development of a Virtual Tumor, CViT

    Directory of Open Access Journals (Sweden)

    Sean Martin

    2007-01-01

    Full Text Available Integrative cancer biology research relies on a variety of data-driven computational modeling and simulation methods and techniques geared towards gaining new insights into the complexity of biological processes that are of critical importance for cancer research. These include the dynamics of gene-protein interaction networks, the percolation of subcellular perturbations across scales and the impact they may have on tumorigenesis in both experiments and clinics. Such innovative ‘systems’ research will greatly benefi t from enabling Information Technology that is currently under development, including an online collaborative environment, a Semantic Web based computing platform that hosts data and model repositories as well as high-performance computing access. Here, we present one of the National Cancer Institute’s recently established Integrative Cancer Biology Programs, i.e. the Center for the Development of a Virtual Tumor, CViT, which is charged with building a cancer modeling community, developing the aforementioned enabling technologies and fostering multi-scale cancer modeling and simulation.

  4. Integration of principles of systems biology and radiation biology: toward development of in silico models to optimize IUdR-mediated radiosensitization of DNA mismatch repair-deficient (damage tolerant human cancers

    Directory of Open Access Journals (Sweden)

    Timothy James Kinsella

    2011-08-01

    Full Text Available Over the last 7 years, we have focused our experimental and computational research efforts on improving our understanding of the biochemical, molecular, and cellular processing of iododeoxyuridine (IUdR and ionizing radiation (IR induced DNA base damage by DNA mismatch repair (MMR. These coordinated research efforts, sponsored by the National Cancer Institute Integrative Cancer Biology Program (ICBP, brought together system scientists with expertise in engineering, mathematics, and complex systems theory and translational cancer researchers with expertise in radiation biology. Our overall goal was to begin to develop computational models of IUdR- and/or IR- induced base damage processing by MMR that may provide new clinical strategies to optimize IUdR-mediated radiosensitiztion in MMR deficient (MMR- damage tolerant human cancers. Using multiple scales of experimental testing, ranging from purified protein systems to in vitro (cellular and to in vivo (human tumor xenografts in athymic mice models, we have begun to integrate and interpolate these experimental data with hybrid stochastic biochemical models of MMR damage processing and probabilistic cell cycle regulation models through a systems biology approach. In this article, we highlight the results and current status of our integration of radiation biology approaches and computational modeling to enhance IUdR-mediated radiosensitization in MMR- damage tolerant cancers.

  5. Engineering scalable biological systems

    OpenAIRE

    Lu, Timothy K.

    2010-01-01

    Synthetic biology is focused on engineering biological organisms to study natural systems and to provide new solutions for pressing medical, industrial, and environmental problems. At the core of engineered organisms are synthetic biological circuits that execute the tasks of sensing inputs, processing logic, and performing output functions. In the last decade, significant progress has been made in developing basic designs for a wide range of biological circuits in bacteria, yeast, and mammal...

  6. Genetics and molecular biology of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    King, M.C. [California Univ., Berkeley, CA (United States); Lippman, M. [Georgetown Univ. Medical Center, Washington, DC (United States)] [comps.

    1992-12-31

    This volume contains the abstracts of oral presentations and poster sessions presented at the Cold Springs Harbor Meeting on Cancer Cells, this meeting entitled Genetics and Molecular Biology of Breast Cancer.

  7. Biological markers of invasive breast cancer.

    Science.gov (United States)

    Matsumoto, Akiko; Jinno, Hiromitsu; Ando, Tomofumi; Fujii, Taku; Nakamura, Tetsuya; Saito, Junichi; Takahashi, Maiko; Hayashida, Tetsu; Kitagawa, Yuko

    2016-02-01

    Biological markers for breast cancer are biomolecules that result from cancer-related processes and are associated with particular clinical outcomes; they thus help predict responses to therapy. In recent years, gene expression profiling has made the molecular classification of breast cancer possible. Classification of breast cancer by immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki-67 is standard practice for clinical decision-making. Assessments of hormone receptor expression and human epidermal growth factor receptor 2 overexpression help estimate benefits from targeted therapies and have greatly improved prognoses for women with these breast cancer types. Although Ki-67 positivity is associated with an adverse outcome, its clear identification is an aid to optimal disease management. Standardization of testing methodology to minimize inter-laboratory measurement variations is a remaining issue. Multi-gene assays provide prognostic information and identify those most likely to benefit from systemic chemotherapy. Incorporating molecular profiles with conventional pathological classification would be more precise, and could enhance the clinical development of personalized therapy in breast cancer. PMID:26486826

  8. Systems biology modeling reveals a possible mechanism of the tumor cell death upon oncogene inactivation in EGFR addicted cancers.

    Directory of Open Access Journals (Sweden)

    Jian-Ping Zhou

    Full Text Available Despite many evidences supporting the concept of "oncogene addiction" and many hypotheses rationalizing it, there is still a lack of detailed understanding to the precise molecular mechanism underlying oncogene addiction. In this account, we developed a mathematic model of epidermal growth factor receptor (EGFR associated signaling network, which involves EGFR-driving proliferation/pro-survival signaling pathways Ras/extracellular-signal-regulated kinase (ERK and phosphoinositol-3 kinase (PI3K/AKT, and pro-apoptotic signaling pathway apoptosis signal-regulating kinase 1 (ASK1/p38. In the setting of sustained EGFR activation, the simulation results show a persistent high level of proliferation/pro-survival effectors phospho-ERK and phospho-AKT, and a basal level of pro-apoptotic effector phospho-p38. The potential of p38 activation (apoptotic potential due to the elevated level of reactive oxygen species (ROS is largely suppressed by the negative crosstalk between PI3K/AKT and ASK1/p38 pathways. Upon acute EGFR inactivation, the survival signals decay rapidly, followed by a fast increase of the apoptotic signal due to the release of apoptotic potential. Overall, our systems biology modeling together with experimental validations reveals that inhibition of survival signals and concomitant release of apoptotic potential jointly contribute to the tumor cell death following the inhibition of addicted oncogene in EGFR addicted cancers.

  9. Prediction in the face of uncertainty: a Monte Carlo-based approach for systems biology of cancer treatment.

    Science.gov (United States)

    Wierling, Christoph; Kühn, Alexander; Hache, Hendrik; Daskalaki, Andriani; Maschke-Dutz, Elisabeth; Peycheva, Svetlana; Li, Jian; Herwig, Ralf; Lehrach, Hans

    2012-08-15

    Cancer is known to be a complex disease and its therapy is difficult. Much information is available on molecules and pathways involved in cancer onset and progression and this data provides a valuable resource for the development of predictive computer models that can help to identify new potential drug targets or to improve therapies. Modeling cancer treatment has to take into account many cellular pathways usually leading to the construction of large mathematical models. The development of such models is complicated by the fact that relevant parameters are either completely unknown, or can at best be measured under highly artificial conditions. Here we propose an approach for constructing predictive models of such complex biological networks in the absence of accurate knowledge on parameter values, and apply this strategy to predict the effects of perturbations induced by anti-cancer drug target inhibitions on an epidermal growth factor (EGF) signaling network. The strategy is based on a Monte Carlo approach, in which the kinetic parameters are repeatedly sampled from specific probability distributions and used for multiple parallel simulations. Simulation results from different forms of the model (e.g., a model that expresses a certain mutation or mutation pattern or the treatment by a certain drug or drug combination) can be compared with the unperturbed control model and used for the prediction of the perturbation effects. This framework opens the way to experiment with complex biological networks in the computer, likely to save costs in drug development and to improve patient therapy.

  10. Biology of cancer and aging.

    Science.gov (United States)

    Holmes, F F; Wilson, J; Blesch, K S; Kaesberg, P R; Miller, R; Sprott, R

    1991-12-01

    The greatest risk factor for cancer is aging. Human cancer incidence increases exponentially with advancing age. Cancer growth rate and potential for metastatic spread may be influenced by age-specific change in host response. Because cancer and aging are, thus, inextricably linked, the American Cancer Society should encourage submission of research proposals that address the mechanisms of aging and how aging alters cancer development.

  11. Molecular biology of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Miroslav Zavoral; Petra Minarikova; Filip Zavada; Cyril Salek; Marek Minarik

    2011-01-01

    In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

  12. The molecular biology of cancer.

    Science.gov (United States)

    Bertram, J S

    2000-12-01

    identifies key genes directly involved in carcinogenesis and demonstrates how mutations in these genes allow cells to circumvent cellular controls. This detailed understanding of the process of carcinogenesis at the molecular level has only been possible because of the advent of modern molecular biology. This new discipline, by precisely identifying the molecular basis of the differences between normal and malignant cells, has created novel opportunities and provided the means to specifically target these modified genes. Whenever possible this review highlights these opportunities and the attempts being made to generate novel, molecular based therapies against cancer. Successful use of these new therapies will rely upon a detailed knowledge of the genetic defects in individual tumors. The review concludes with a discussion of how the use of high throughput molecular arrays will allow the molecular pathologist/therapist to identify these defects and direct specific therapies to specific mutations.

  13. Systems cell biology.

    Science.gov (United States)

    Mast, Fred D; Ratushny, Alexander V; Aitchison, John D

    2014-09-15

    Systems cell biology melds high-throughput experimentation with quantitative analysis and modeling to understand many critical processes that contribute to cellular organization and dynamics. Recently, there have been several advances in technology and in the application of modeling approaches that enable the exploration of the dynamic properties of cells. Merging technology and computation offers an opportunity to objectively address unsolved cellular mechanisms, and has revealed emergent properties and helped to gain a more comprehensive and fundamental understanding of cell biology.

  14. Molecular Biology of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    HuanXi; JanBrabender; RalfMetzger; PaulM.Schneider

    2004-01-01

    There have been many new developments in our understanding of esophageal carcinoma biology over the past several years. Information regarding both of the major forms of this disease, adenocarcinoma and squamous cell carcinoma, has accumulated in conjunction with data on precursor conditions such as Barrett's esophagus. Interesting and promising findings have included overexpression of proto-oncogenes,loss of heterozygosity at multiple chromosomal loci, tumor suppressor gene inactivation, epigenetic silencing by DNA methylation, and mutations and deletions involving the tumor suppressor gene p53. Important cancer pathways, the cyclin kinase inhibitor cascade and the DNA mismatch repair process, implicated in the genesis of multiple tumor types have also been inculpated in esophageal carcinogenesis. Alterations in the p16 and p15 cyclin kinase inhibitors including point mutations and homozygous deletions have been reported in primary esophageal tumors. Further developments in the field of molecular carcinogenesis of esophageal malignancies promise to yield improvements in prevention, early detection, prognostic categorization, and perhaps gene-based therapy of this deadly disease.

  15. Identification of clinically relevant protein targets in prostate cancer with 2D-DIGE coupled mass spectrometry and systems biology network platform.

    Directory of Open Access Journals (Sweden)

    Ramesh Ummanni

    Full Text Available Prostate cancer (PCa is the most common type of cancer found in men and among the leading causes of cancer death in the western world. In the present study, we compared the individual protein expression patterns from histologically characterized PCa and the surrounding benign tissue obtained by manual micro dissection using highly sensitive two-dimensional differential gel electrophoresis (2D-DIGE coupled with mass spectrometry. Proteomic data revealed 118 protein spots to be differentially expressed in cancer (n = 24 compared to benign (n = 21 prostate tissue. These spots were analysed by MALDI-TOF-MS/MS and 79 different proteins were identified. Using principal component analysis we could clearly separate tumor and normal tissue and two distinct tumor groups based on the protein expression pattern. By using a systems biology approach, we could map many of these proteins both into major pathways involved in PCa progression as well as into a group of potential diagnostic and/or prognostic markers. Due to complexity of the highly interconnected shortest pathway network, the functional sub networks revealed some of the potential candidate biomarker proteins for further validation. By using a systems biology approach, our study revealed novel proteins and molecular networks with altered expression in PCa. Further functional validation of individual proteins is ongoing and might provide new insights in PCa progression potentially leading to the design of novel diagnostic and therapeutic strategies.

  16. Plant Systems Biology (editorial)

    Science.gov (United States)

    In June 2003, Plant Physiology published an Arabidopsis special issue devoted to plant systems biology. The intention of Natasha Raikhel and Gloria Coruzzi, the two editors of this first-of-its-kind issue, was ‘‘to help nucleate this new effort within the plant community’’ as they considered that ‘‘...

  17. 7th Annual Systems Biology Symposium: Systems Biology and Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Galitski, Timothy P.

    2008-04-01

    Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology has been hosted by the Institute for Systems Biology in Seattle, Washington, since 2002. The annual two-day event gathers the most influential researchers transforming biology into an integrative discipline investingating complex systems. Engineering and application of new technology is a central element of systems biology. Genome-scale, or very small-scale, biological questions drive the enigneering of new technologies, which enable new modes of experimentation and computational analysis, leading to new biological insights and questions. Concepts and analytical methods in engineering are now finding direct applications in biology. Therefore, the 2008 Symposium, funded in partnership with the Department of Energy, featured global leaders in "Systems Biology and Engineering."

  18. Biological Response Modifier in Cancer Immunotherapy.

    Science.gov (United States)

    Liu, Ronghua; Luo, Feifei; Liu, Xiaoming; Wang, Luman; Yang, Jiao; Deng, Yuting; Huang, Enyu; Qian, Jiawen; Lu, Zhou; Jiang, Xuechao; Zhang, Dan; Chu, Yiwei

    2016-01-01

    Biological response modifiers (BRMs) emerge as a lay of new compounds or approaches used in improving cancer immunotherapy. Evidences highlight that cytokines, Toll-like receptor (TLR) signaling, and noncoding RNAs are of crucial roles in modulating antitumor immune response and cancer-related chronic inflammation, and BRMs based on them have been explored. In particular, besides some cytokines like IFN-α and IL-2, several Toll-like receptor (TLR) agonists like BCG, MPL, and imiquimod are also licensed to be used in patients with several malignancies nowadays, and the first artificial small noncoding RNA (microRNA) mimic, MXR34, has entered phase I clinical study against liver cancer, implying their potential application in cancer therapy. According to amounts of original data, this chapter will review the regulatory roles of TLR signaling, some noncoding RNAs, and several key cytokines in cancer and cancer-related immune response, as well as the clinical cases in cancer therapy based on them.

  19. Integrative radiation systems biology

    International Nuclear Information System (INIS)

    Maximisation of the ratio of normal tissue preservation and tumour cell reduction is the main concept of radiotherapy alone or combined with chemo-, immuno- or biologically targeted therapy. The foremost parameter influencing this ratio is radiation sensitivity and its modulation towards a more efficient killing of tumour cells and a better preservation of normal tissue at the same time is the overall aim of modern therapy schemas. Nevertheless, this requires a deep understanding of the molecular mechanisms of radiation sensitivity in order to identify its key players as potential therapeutic targets. Moreover, the success of conventional approaches that tried to statistically associate altered radiation sensitivity with any molecular phenotype such as gene expression proofed to be somewhat limited since the number of clinically used targets is rather sparse. However, currently a paradigm shift is taking place from pure frequentistic association analysis to the rather holistic systems biology approach that seeks to mathematically model the system to be investigated and to allow the prediction of an altered phenotype as the function of one single or a signature of biomarkers. Integrative systems biology also considers the data from different molecular levels such as the genome, transcriptome or proteome in order to partially or fully comprehend the causal chain of molecular mechanisms. An example for the application of this concept currently carried out at the Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer” of the Helmholtz-Zentrum München and the LMU Munich is described. This review article strives for providing a compact overview on the state of the art of systems biology, its actual challenges, potential applications, chances and limitations in radiation oncology research working towards improved personalised therapy concepts using this relatively new methodology

  20. Systems biology, emergence and antireductionism.

    Science.gov (United States)

    Kesić, Srdjan

    2016-09-01

    This study explores the conceptual history of systems biology and its impact on philosophical and scientific conceptions of reductionism, antireductionism and emergence. Development of systems biology at the beginning of 21st century transformed biological science. Systems biology is a new holistic approach or strategy how to research biological organisms, developed through three phases. The first phase was completed when molecular biology transformed into systems molecular biology. Prior to the second phase, convergence between applied general systems theory and nonlinear dynamics took place, hence allowing the formation of systems mathematical biology. The second phase happened when systems molecular biology and systems mathematical biology, together, were applied for analysis of biological data. Finally, after successful application in science, medicine and biotechnology, the process of the formation of modern systems biology was completed. Systems and molecular reductionist views on organisms were completely opposed to each other. Implications of systems and molecular biology on reductionist-antireductionist debate were quite different. The analysis of reductionism, antireductionism and emergence issues, in the era of systems biology, revealed the hierarchy between methodological, epistemological and ontological antireductionism. Primarily, methodological antireductionism followed from the systems biology. Only after, epistemological and ontological antireductionism could be supported.

  1. The biology of cancer stem cells.

    Science.gov (United States)

    Lobo, Neethan A; Shimono, Yohei; Qian, Dalong; Clarke, Michael F

    2007-01-01

    Cancers originally develop from normal cells that gain the ability to proliferate aberrantly and eventually turn malignant. These cancerous cells then grow clonally into tumors and eventually have the potential to metastasize. A central question in cancer biology is, which cells can be transformed to form tumors? Recent studies elucidated the presence of cancer stem cells that have the exclusive ability to regenerate tumors. These cancer stem cells share many characteristics with normal stem cells, including self-renewal and differentiation. With the growing evidence that cancer stem cells exist in a wide array of tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because corruption of genes involved in these pathways likely participates in tumor growth. This new paradigm of oncogenesis has been validated in a growing list of tumors. Studies of normal and cancer stem cells from the same tissue have shed light on the ontogeny of tumors. That signaling pathways such as Bmi1 and Wnt have similar effects in normal and cancer stem cell self-renewal suggests that common molecular pathways regulate both populations. Understanding the biology of cancer stem cells will contribute to the identification of molecular targets important for future therapies.

  2. Testicular cancer: biology and biomarkers.

    Science.gov (United States)

    Looijenga, Leendert H J; Stoop, Hans; Biermann, Katharina

    2014-03-01

    The term "human germ cell tumors" (GCTs) refers to a heterogeneous group of neoplasms, all with a defined histological appearance. They have specific epidemiological characteristics, clinical behavior, and pathogenesis. Histologically, GCTs contain various tissue elements, which are homologs of normal embryogenesis. We have proposed a subclassification of GCTs in five subtypes, three of which preferentially occur in the testis. These include teratomas and yolk sac tumors of neonates and infants (type I), seminomas and nonseminomas of (predominantly) adolescents and adults (type II), and spermatocytic seminomas of the elderly (type III). Both spontaneous and induced animal models have been reported, of which the relevance for human GCTs is still to be clarified. Multidisciplinary studies have recently shed new light on the (earliest steps in the) pathogenesis of GCTs, mainly in regard of malignant type II GCTs (germ cell cancer (GCC)). This review discusses novel understanding of the pathogenesis of (mainly) GCC, focusing on identification of informative diagnostic markers suitable for application in a clinical setting. These include OCT3/4, SOX9/FOXL2, SOX17/SOX2, as well as embryonic microRNAs. These markers have been identified through studies on normal embryogenesis, specifically related to the gonads, including the germ cell lineage. Their strengths and limitations are discussed as well as the expected future approach to identify the group of individuals at highest risk for development of a GCC. The latter would allow screening of defined populations, early diagnosis, optimal follow-up, and potentially early treatment, preventing long-term side effects of systemic treatment. PMID:24487784

  3. TFPI alpha and beta regulate mRNAs and microRNAs involved in cancer biology and in the immune system in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Benedicte Stavik

    Full Text Available Emerging evidence indicate a new role of TFPI in cancer biology. We recently reported that both isoforms of TFPI induced apoptosis and inhibited proliferation of cancer cells. The signaling pathway(s mediating the effects of TFPI is, however, presently still unclear. Our goal was to further investigate the cellular processes affected by TFPI and to get insight into the molecular mechanisms involved in the effects of TFPI, using a global gene expression study approach. TFPIα or TFPIβ cDNA were transfected into SK-BR-3 breast cancer cells for stable overexpression. Global mRNA and microRNA (miRNA expressions were measured and functional annotation of the differentially expressed genes and miRNAs according to gene ontology terms was conducted. Selected results were validated using qRT-PCR and Western blot. A total of 242 and 801 mRNA transcripts and 120 and 46 miRNAs were differentially expressed in cells overexpressing TFPIα or TFPIβ, respectively. Overexpression of either isoform significantly affected the expression of genes involved in cell development (apoptosis, cell movement, migration, invasion, colony formation, growth, and adhesion and immune response. Network analyses revealed biological interactions between these genes and implied that several of the genes may be involved in both processes. The expression profiles also correlated significantly with clinical phenotype and outcome. Functional cluster analyses indicated altered activity of the epidermal growth factor receptor, small GTPases, and the NF-κB and JAK/STAT cascades when TFPI was overexpressed, and increased activity of the transcription factors NF-κB and Elk-1 and phospho-Akt levels was observed. Integrated mRNA-miRNA analyses showed that 19% and 32% of the differentially expressed genes in cells overexpressing TFPIα or TFPIβ, respectively, may have been regulated by miRNAs. Overexpression of TFPI in breast cancer cells affected the expression of mRNAs and mi

  4. Systems biology in animal sciences

    NARCIS (Netherlands)

    Woelders, H.; Pas, te M.F.W.; Bannink, A.; Veerkamp, R.F.; Smits, M.A.

    2011-01-01

    Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes an

  5. The common biology of cancer and ageing.

    Science.gov (United States)

    Finkel, Toren; Serrano, Manuel; Blasco, Maria A

    2007-08-16

    At first glance, cancer and ageing would seem to be unlikely bedfellows. Yet the origins for this improbable union can actually be traced back to a sequence of tragic--and some say unethical--events that unfolded more than half a century ago. Here we review the series of key observations that has led to a complex but growing convergence between our understanding of the biology of ageing and the mechanisms that underlie cancer.

  6. Logical analysis of biological systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian

    2005-01-01

    R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005.......R. Mardare, Logical analysis of biological systems. Fundamenta Informaticae, N 64:271-285, 2005....

  7. ECO-BIOLOGICAL SYSTEM MODELING

    Directory of Open Access Journals (Sweden)

    T. I. Burak

    2015-01-01

    Full Text Available The methodology for computer modeling of complex eco-biological models is presented in this paper. It is based on system approach of J. Forrester. Developed methodology is universal for complex ecological and biological systems. Modeling algorithm considers specialties of eco-biological systems and shows adequate and accurate results in practice. 

  8. Wnt Signaling in Cancer Stem Cell Biology.

    Science.gov (United States)

    de Sousa E Melo, Felipe; Vermeulen, Louis

    2016-06-27

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer.

  9. Wnt Signaling in Cancer Stem Cell Biology

    Science.gov (United States)

    de Sousa e Melo, Felipe; Vermeulen, Louis

    2016-01-01

    Aberrant regulation of Wnt signaling is a common theme seen across many tumor types. Decades of research have unraveled the epigenetic and genetic alterations that result in elevated Wnt pathway activity. More recently, it has become apparent that Wnt signaling levels identify stem-like tumor cells that are responsible for fueling tumor growth. As therapeutic targeting of these tumor stem cells is an intense area of investigation, a concise understanding on how Wnt activity relates to cancer stem cell traits is needed. This review attempts at summarizing the intricacies between Wnt signaling and cancer stem cell biology with a special emphasis on colorectal cancer. PMID:27355964

  10. Biological functions of decorin in cancer

    Institute of Scientific and Technical Information of China (English)

    Xiu-Li Bi; Wancai Yang

    2013-01-01

    Decorin is a member of the extracellular matrix small leucine-rich proteoglycans family that exists and functions in stromal and epithelial cells.Accumulating evidence suggests that decorin affects the biology of various types of cancer by directly or indirectly targeting the signaling molecules involved in cell growth,survival,metastasis,and angiogenesis.More recent studies show that decorin plays important roles during tumor development and progression and is a potential cancer therapeutic agent.In this article,we summarize recent studies of decorin in cancer and discuss decorin's therapeutic and prognostic value.

  11. Estimation of lead in biological samples of oral cancer patients chewing smokeless tobacco products by ionic liquid-based microextraction in a single syringe system.

    Science.gov (United States)

    Arain, Sadaf S; Kazi, Tasneem G; Arain, Asma J; Afridi, Hassan I; Arain, Muhammad B; Brahman, Kapil D; Naeemullah; Panhwar, Abdul H; Arain, Mariam S

    2015-08-01

    Several studies have reported that the chewing habit of smokeless tobacco (SLT) has been associated with oral cancer. The aim of the present study was to evaluate the trace levels of lead (Pb) in biological samples (blood, scalp hair) of oral cancer patients and referents of the same age group (range 30-60 years). As the concentrations of Pb are very low in biological samples, so a simple and efficient ionic liquid-based microextraction in a single syringe system has been developed, as a prior step to determination by flame atomic absorption spectrometry. In this procedure, the hydrophobic chelates of Pb with ammonium pyrrolidinedithiocarbamate (APDC) were extracted into fine droplets of 1-butyl-3-methylimidazolium hexafluorophosphate [C4MIM][PF6] within a syringe while using Triton X-114 as a dispersant. Factors influencing the microextraction efficiency and determination, such as pH of the sample, volume of [C4MIM][PF6] and Triton X-114, ligand concentration, and incubation time, were studied. To validate the proposed method, certified reference materials were analyzed and the results of Pb(2+) were in good agreement with certified values. At optimum experimental values of significant variables, detection limit and enhancement factor were found to be 0.412 μg/L and 80, respectively. The coexisting ions showed no obvious negative outcome on Pb preconcentration. The proposed method was applied satisfactorily for the preconcentration of Pb(2+) in acid-digested SLT and biological samples of the study population. It was observed that oral cancer patients who consumed different SLT products have 2-3-fold higher levels of Pb in scalp hair and blood samples as compared to healthy referents (p < 0.001). While 31.4-50.8% higher levels of Pb were observed in referents chewing different SLT products as compared to nonconsumers (p < 0.01).

  12. Estimation of lead in biological samples of oral cancer patients chewing smokeless tobacco products by ionic liquid-based microextraction in a single syringe system.

    Science.gov (United States)

    Arain, Sadaf S; Kazi, Tasneem G; Arain, Asma J; Afridi, Hassan I; Arain, Muhammad B; Brahman, Kapil D; Naeemullah; Panhwar, Abdul H; Arain, Mariam S

    2015-08-01

    Several studies have reported that the chewing habit of smokeless tobacco (SLT) has been associated with oral cancer. The aim of the present study was to evaluate the trace levels of lead (Pb) in biological samples (blood, scalp hair) of oral cancer patients and referents of the same age group (range 30-60 years). As the concentrations of Pb are very low in biological samples, so a simple and efficient ionic liquid-based microextraction in a single syringe system has been developed, as a prior step to determination by flame atomic absorption spectrometry. In this procedure, the hydrophobic chelates of Pb with ammonium pyrrolidinedithiocarbamate (APDC) were extracted into fine droplets of 1-butyl-3-methylimidazolium hexafluorophosphate [C4MIM][PF6] within a syringe while using Triton X-114 as a dispersant. Factors influencing the microextraction efficiency and determination, such as pH of the sample, volume of [C4MIM][PF6] and Triton X-114, ligand concentration, and incubation time, were studied. To validate the proposed method, certified reference materials were analyzed and the results of Pb(2+) were in good agreement with certified values. At optimum experimental values of significant variables, detection limit and enhancement factor were found to be 0.412 μg/L and 80, respectively. The coexisting ions showed no obvious negative outcome on Pb preconcentration. The proposed method was applied satisfactorily for the preconcentration of Pb(2+) in acid-digested SLT and biological samples of the study population. It was observed that oral cancer patients who consumed different SLT products have 2-3-fold higher levels of Pb in scalp hair and blood samples as compared to healthy referents (p < 0.001). While 31.4-50.8% higher levels of Pb were observed in referents chewing different SLT products as compared to nonconsumers (p < 0.01). PMID:25903188

  13. Molecular biology of the lung cancer

    International Nuclear Information System (INIS)

    Background. Lung cancer is one of the most common malignant diseases and leading cause of cancer death worldwide. The advances in molecular biology and genetics, including the modern microarray technology and rapid sequencing techniques, have enabled a remarkable progress into elucidating the lung cancer ethiopathogenesis. Numerous studies suggest that more than 20 different genetic and epigenetic alterations are accumulating during the pathogenesis of clinically evident pulmonary cancers as a clonal, multistep process. Thus far, the most investigated alterations are the inactivational mutations and losses of tumour suppressor genes and the overexpression of growth-promoting oncogenes. More recently, the acquired epigenetic inactivation of tumour suppressor genes by promoter hypermethylation has been recognized. The early clonal genetic abnormalities that occur in preneoplastic bronchial epithelium damaged by smoking or other carcinogenes are being identified. The molecular distinctions between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), as well as between tumors with different clinical outcomes have been described. These investigations lead to the hallmarks of lung cancer. Conclusions. It is realistic to expect that the molecular and cell culture-based investigations will lead to discoveries of new clinical applications with the potential to provide new avenues for early diagnosis, risk assessment, prevention, and most important, new more effective treatment approaches for the lung cancer patients. (author)

  14. Biology of cancer: some questions to answer.

    Science.gov (United States)

    Chapekar, T

    2001-10-01

    Though great advances in cancer biology have taken place through these years, some fundamental questions are still to be explained. Some observations in this regard are discussed in the present paper. In the course of experimental studies on hormonal stimulation of target cells, it was observed that goat granulosa cells showed differential proliferative response to sustained stimulation by oLH and hCG in culture. oLH caused cells to proliferate whereas hCG failed to stimulate the cells though both the gonadotropins have common receptors on the target cell. Further studies might throw some light on the mechanism of signal transduction in cell biology and neoplasia. A question is also posed as to how to interpret thermodynamically the sustained growth of cancer vis-a-vis the host.

  15. Systems Biology Approaches for the Prediction of Possible Role of Chlamydia pneumoniae Proteins in the Etiology of Lung Cancer.

    Science.gov (United States)

    Khan, Shahanavaj; Imran, Ahamad; Khan, Abdul Arif; Abul Kalam, Mohd; Alshamsan, Aws

    2016-01-01

    Accumulating evidence has recently supported the association of bacterial infection with the growth and development of cancers, particularly in organs that are constantly exposed to bacteria such as the lungs, colon, cervical cancer etc. Our in silico study on the proteome of Chlamydia pneumoniae suggests an unprecedented idea of the etiology of lung cancer and have revealed that the infection of C. pneumoniae is associated with lung cancer development and growth. It is reasonable to assume that C. pneumoniae transports its proteins within host-intracellular organelles during infection, where they may work with host-cell proteome. The current study was performed for the prediction of nuclear targeting protein of C. pneumoniae in the host cell using bioinformatics predictors including ExPASy pI/Mw tool, nuclear localization signal (NLS) mapper, balanced sub cellular localization predictor (BaCeILo), and Hum-mPLoc 2.0. We predicted 47/1112 nuclear-targeting proteins of C. pneumoniae connected with several possible alterations in host replication and transcription during intracellular infection. These nuclear-targeting proteins may direct to competitive interactions of host and C. pneumoniae proteins with the availability of same substrate and may be involved as etiological agents in the growth and development of lung cancer. These novel findings are expected to access in better understanding of lung cancer etiology and identifying molecular targets for therapy.

  16. Mapping biological systems to network systems

    CERN Document Server

    Rathore, Heena

    2016-01-01

    The book presents the challenges inherent in the paradigm shift of network systems from static to highly dynamic distributed systems – it proposes solutions that the symbiotic nature of biological systems can provide into altering networking systems to adapt to these changes. The author discuss how biological systems – which have the inherent capabilities of evolving, self-organizing, self-repairing and flourishing with time – are inspiring researchers to take opportunities from the biology domain and map them with the problems faced in network domain. The book revolves around the central idea of bio-inspired systems -- it begins by exploring why biology and computer network research are such a natural match. This is followed by presenting a broad overview of biologically inspired research in network systems -- it is classified by the biological field that inspired each topic and by the area of networking in which that topic lies. Each case elucidates how biological concepts have been most successfully ...

  17. Telemetry System of Biological Parameters

    Directory of Open Access Journals (Sweden)

    Jan Spisak

    2005-01-01

    Full Text Available The mobile telemetry system of biological parameters serves for reading and wireless data transfer of measured values of selected biological parameters to an outlying computer. It concerns basically long time monitoring of vital function of car pilot.The goal of this projects is to propose mobile telemetry system for reading, wireless transfer and processing of biological parameters of car pilot during physical and psychical stress. It has to be made with respect to minimal consumption, weight and maximal device mobility. This system has to eliminate signal noise, which is created by biological artifacts and disturbances during the data transfer.

  18. Telemetry System of Biological Parameters

    OpenAIRE

    2005-01-01

    The mobile telemetry system of biological parameters serves for reading and wireless data transfer of measured values of selected biological parameters to an outlying computer. It concerns basically long time monitoring of vital function of car pilot.The goal of this projects is to propose mobile telemetry system for reading, wireless transfer and processing of biological parameters of car pilot during physical and psychical stress. It has to be made with respect to minimal consum...

  19. Breast cancer. From molecular biology to personified therapy

    Directory of Open Access Journals (Sweden)

    Bondarenko I.N.

    2016-03-01

    Full Text Available Advances in molecular biology had changed approaches to systemic treatment of breast cancer. Clinical decisions on the choice of optimal treatment regimens are performing on the basis of immunohistochemical and molecular genetic classifications. Their increasing uses have contributed changes of paradigm for cancer treatment - from the empirical to the individualized and personalized. The basis for such approaches is knowledge of molecular epidemiology, heterogeneity of expression of molecular subtypes, prognostic and predictive biomarkers of breast cancer. Breast cancer is a widely heterogeneous disease with 20 histological types, 8, molecular-genetic, 6 genomic subtypes, which are characterized by specific molecular and biochemical properties, different clinical course and different outcomes. Molecular genetic classification, created not on the basis of clinical, anatomical and morphological heterogeneity of tumor cells, and on the basis of their molecular-genetic heterogeneity is widely used in clinical practice. This allowed to separate the patients with breast cancer to molecular 4 subtypes - luminal A, luminal B, HER / 2 positive and triple-negative. The significant role of immunohistochemical tissue tumor markers, estrogen and progesterone receptors, HER / 2-neu, Ki-67, p53 for selection the optimal treatment strategy is analyzing in this review. To increase the effectiveness of breast cancer treatment is possible, using a differentiated and personalized approach based on new molecular genetic classification of breast cancer (gene profiling or to its analogue - expression classification of breast cancer, based on the principle of diversity of immunohistochemical tumor tissue. Personification of cancer treatment involves a therapy based on the study of individual characteristics of tissue is not only the primary tumor but also its metastases. Citation: Bondarenko IN, Elhajj Mohammad H, Prokhach AV, Zavizion VF, Chebanov KO. [Breast cancer

  20. Static Analysis for Systems Biology

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nielson, Hanne Riis; Rosa, D. Schuch da;

    2004-01-01

    This paper shows how static analysis techniques can help understanding biological systems. Based on a simple example we illustrate the outcome of performing three different analyses extracting information of increasing precision. We conclude by reporting on the potential impact and exploitation o...... of these techniques in systems biology....

  1. Quantum Effects in Biological Systems

    CERN Document Server

    2016-01-01

    Since the last decade the study of quantum mechanical phenomena in biological systems has become a vibrant field of research. Initially sparked by evidence of quantum effects in energy transport that is instrumental for photosynthesis, quantum biology asks the question of how methods and models from quantum theory can help us to understand fundamental mechanisms in living organisms. This approach entails a paradigm change challenging the related disciplines: The successful framework of quantum theory is taken out of its low-temperature, microscopic regimes and applied to hot and dense macroscopic environments, thereby extending the toolbox of biology and biochemistry at the same time. The Quantum Effects in Biological Systems conference is a platform for researchers from biology, chemistry and physics to present and discuss the latest developments in the field of quantum biology. After meetings in Lisbon (2009), Harvard (2010), Ulm (2011), Berkeley (2012), Vienna (2013), Singapore (2014) and Florence (2015),...

  2. Nutritional Systems Biology

    DEFF Research Database (Denmark)

    Jensen, Kasper

    and network biology has the potential to increase our understanding of how small molecules affect metabolic pathways and homeostasis, how this perturbation changes at the disease state, and to what extent individual genotypes contribute to this. A fruitful strategy in approaching and exploring the field...... of nutritional research is, therefore, to borrow methods that are well established in medical and pharmacological research. In this thesis, we use advanced data-mining tools for the construction of a database with available, state-of-the-art information concerning the interaction of food and its molecular...

  3. Mechanistic Effects of Calcitriol in Cancer Biology

    Directory of Open Access Journals (Sweden)

    Lorenza Díaz

    2015-06-01

    Full Text Available Besides its classical biological effects on calcium and phosphorus homeostasis, calcitriol, the active vitamin D metabolite, has a broad variety of actions including anticancer effects that are mediated either transcriptionally and/or via non-genomic pathways. In the context of cancer, calcitriol regulates the cell cycle, induces apoptosis, promotes cell differentiation and acts as anti-inflammatory factor within the tumor microenvironment. In this review, we address the different mechanisms of action involved in the antineoplastic effects of calcitriol.

  4. Inflammatory mediators: Parallels between cancer biology and stem cell therapy

    OpenAIRE

    Patel, Shyam A; Heinrich, Andrew C; Bobby Y. Reddy; Rameshwar, Pranela

    2009-01-01

    Inflammation encompasses diverse molecular pathways, and it is intertwined with a wide array of biological processes. Recently, there has been an upsurge of interest in the interactions between mediators of inflammation and other cells such as stem cells and cancer cells. Since tissue injuries are associated with the release of inflammatory mediators, it would be difficult to address this subject without considering the implications of their systemic effects. In this review, we discuss the ef...

  5. Aging and computational systems biology.

    Science.gov (United States)

    Mooney, Kathleen M; Morgan, Amy E; Mc Auley, Mark T

    2016-01-01

    Aging research is undergoing a paradigm shift, which has led to new and innovative methods of exploring this complex phenomenon. The systems biology approach endeavors to understand biological systems in a holistic manner, by taking account of intrinsic interactions, while also attempting to account for the impact of external inputs, such as diet. A key technique employed in systems biology is computational modeling, which involves mathematically describing and simulating the dynamics of biological systems. Although a large number of computational models have been developed in recent years, these models have focused on various discrete components of the aging process, and to date no model has succeeded in completely representing the full scope of aging. Combining existing models or developing new models may help to address this need and in so doing could help achieve an improved understanding of the intrinsic mechanisms which underpin aging.

  6. Modelling coordination in biological systems

    OpenAIRE

    Clarke, David; Oliveira Costa, de, David; Arbab, Farhad

    2004-01-01

    We present an application of the Reo coordination paradigm to provide a compositional formal model for describing and reasoning about the behaviour of biological systems, such as regulatory gene networks. Reo governs the interaction and flow of data between components by allowing the construction of connector circuits which have a precise formal semantics. When applied to systems biology, the result is a graphical model, which is comprehensible, mathematically precise, and flexible

  7. Optimization in computational systems biology

    OpenAIRE

    Banga Julio R

    2008-01-01

    Abstract Optimization aims to make a system or design as effective or functional as possible. Mathematical optimization methods are widely used in engineering, economics and science. This commentary is focused on applications of mathematical optimization in computational systems biology. Examples are given where optimization methods are used for topics ranging from model building and optimal experimental design to metabolic engineering and synthetic biology. Finally, several perspectives for ...

  8. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...... to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many...

  9. Informing Biological Design by Integration of Systems and Synthetic Biology

    OpenAIRE

    Smolke, Christina D.; Silver, Pamela A.

    2011-01-01

    Synthetic biology aims to make the engineering of biology faster and more predictable. In contrast, systems biology focuses on the interaction of myriad components and how these give rise to the dynamic and complex behavior of biological systems. Here, we examine the synergies between these two fields.

  10. Mutant p53: multiple mechanisms define biologic activity in cancer

    Directory of Open Access Journals (Sweden)

    Michael Paul Kim

    2015-11-01

    Full Text Available The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of p53 alterations involve missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may acquire novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in multiple model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 are reviewed and their limitations discussed.

  11. Kinetic Modeling of Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

    Resat, Haluk; Petzold, Linda; Pettigrew, Michel F.

    2009-04-21

    The dynamics of how its constituent components interact define the spatio-temporal response of a natural system to stimuli. Modeling the kinetics of the processes that represent a biophysical system has long been pursued with the aim of improving our understanding of the studied system. Due to the unique properties of biological systems, in addition to the usual difficulties faced in modeling the dynamics of physical or chemical systems, biological simulations encounter difficulties that result from intrinsic multiscale and stochastic nature of the biological processes. This chapter discusses the implications for simulation of models involving interacting species with very low copy numbers, which often occur in biological systems and give rise to significant relative fluctuations. The conditions necessitating the use of stochastic kinetic simulation methods and the mathematical foundations of the stochastic simulation algorithms are presented. How the well-organized structural hierarchies often seen in biological systems can lead to multiscale problems, and possible ways to address the encountered computational difficulties are discussed. We present the details of the existing kinetic simulation methods, and discuss their strengths and shortcomings. A list of the publicly available kinetic simulation tools and our reflections for future prospects are also provided.

  12. Circadian systems biology in Metazoa.

    Science.gov (United States)

    Lin, Li-Ling; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2015-11-01

    Systems biology, which can be defined as integrative biology, comprises multistage processes that can be used to understand components of complex biological systems of living organisms and provides hierarchical information to decoding life. Using systems biology approaches such as genomics, transcriptomics and proteomics, it is now possible to delineate more complicated interactions between circadian control systems and diseases. The circadian rhythm is a multiscale phenomenon existing within the body that influences numerous physiological activities such as changes in gene expression, protein turnover, metabolism and human behavior. In this review, we describe the relationships between the circadian control system and its related genes or proteins, and circadian rhythm disorders in systems biology studies. To maintain and modulate circadian oscillation, cells possess elaborative feedback loops composed of circadian core proteins that regulate the expression of other genes through their transcriptional activities. The disruption of these rhythms has been reported to be associated with diseases such as arrhythmia, obesity, insulin resistance, carcinogenesis and disruptions in natural oscillations in the control of cell growth. This review demonstrates that lifestyle is considered as a fundamental factor that modifies circadian rhythm, and the development of dysfunctions and diseases could be regulated by an underlying expression network with multiple circadian-associated signals.

  13. Nanoscale technology in biological systems

    CERN Document Server

    Greco, Ralph S; Smith, R Lane

    2004-01-01

    Reviewing recent accomplishments in the field of nanobiology Nanoscale Technology in Biological Systems introduces the application of nanoscale matrices to human biology. It focuses on the applications of nanotechnology fabrication to biomedical devices and discusses new physical methods for cell isolation and manipulation and intracellular communication at the molecular level. It also explores the application of nanobiology to cardiovascular diseases, oncology, transplantation, and a range of related disciplines. This book build a strong background in nanotechnology and nanobiology ideal for

  14. Local therapy, systemic benefit: challenging the paradigm of biological predeterminism.

    Science.gov (United States)

    Kurtz, J M

    2006-04-01

    This paper briefly reviews the historical evolution of paradigms that have been purported to characterise the clinical behaviour of breast cancer, with the intention of guiding treatment approaches. Results from randomised clinical trials and the explosion of knowledge in the area of cancer biology have discredited the monolithic paradigms that had dominated thinking about breast cancer in the past. Contemporary notions of breast cancer biology recognise that, although some cancers disseminate well before becoming clinically detectable, acquisition of a metastatic phenotype can occur at any point (or not at all) in the local evolution of the tumour. As a consequence, both systemic and timely local--regional therapies can be expected to influence disease dissemination and patient survival. This is consistent with results observed in clinical trials, overviews of which indicate that prevention of four local recurrences will, on the average, prevent one death from breast cancer. Optimisation of local-regional treatment is an important goal in breast cancer management. PMID:16605046

  15. The evolving biology and treatment of prostate cancer

    OpenAIRE

    Taichman, Russel S.; Loberg, Robert D; Mehra, Rohit; Kenneth J Pienta

    2007-01-01

    Since the effectiveness of androgen deprivation for treatment of advanced prostate cancer was first demonstrated, prevention strategies and medical therapies for prostate cancer have been based on understanding the biologic underpinnings of the disease. Prostate cancer treatment is one of the best examples of a systematic therapeutic approach to target not only the cancer cells themselves, but the microenvironment in which they are proliferating. As the population ages and prostate cancer pre...

  16. Biology of cancer: current issues and future prospects.

    Science.gov (United States)

    Jenkins, J

    1992-02-01

    The future of cancer treatment is limited only by the rate of progress made in understanding the biology of cancer. The future will present a considerable challenge to health care professionals to learn new theories, understand new terms, and expect different toxicities. The explosion of information and technology is exciting, yet frightening. The willingness of scientists, health care professionals, and consumers to deal with the ethical, financial, and political issues generated by this progress is gratifying. Because science has created such advances, the effort to deal with the outcomes is worthwhile but still difficult. The challenge to rapidly facilitate the sharing of the scientific and clinical advances has been recognized by the nation. A legislative mandate to create a way to store and analyze the vast data related to molecular biology, biochemistry, and genetics resulted in the National Center for Biotechnology Information. The development of automated systems to analyze genetic, environmental, biological, and chemistry information can only enhance future progress in the management of cancer.

  17. Ten questions about systems biology

    DEFF Research Database (Denmark)

    Joyner, Michael J; Pedersen, Bente K

    2011-01-01

    In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist...... perspective about the contribution of genes and genetic variants to disease is a key reason 'omics' has failed to deliver the anticipated breakthroughs. We then point out the critical utility of key concepts from physiology like homeostasis, regulated systems and redundancy as major intellectual tools...... to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many...

  18. Bridging the gap between systems biology and synthetic biology

    OpenAIRE

    Liu, Di; Hoynes-O’Connor, Allison; Zhang, Fuzhong

    2013-01-01

    Systems biology is an inter-disciplinary science that studies the complex interactions and the collective behavior of a cell or an organism. Synthetic biology, as a technological subject, combines biological science and engineering, allowing the design and manipulation of a system for certain applications. Both systems and synthetic biology have played important roles in the recent development of microbial platforms for energy, materials, and environmental applications. More importantly, syst...

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

    Science.gov (United States)

    Stites, Edward C.

    2013-04-01

    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.

  20. Systems biology approach to bioremediation

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Romy; Wu, Cindy H.; Hazen, Terry C.

    2012-06-01

    Bioremediation has historically been approached as a ‘black box’ in terms of our fundamental understanding. Thus it succeeds and fails, seldom without a complete understanding of why. Systems biology is an integrated research approach to study complex biological systems, by investigating interactions and networks at the molecular, cellular, community, and ecosystem level. The knowledge of these interactions within individual components is fundamental to understanding the dynamics of the ecosystem under investigation. Finally, understanding and modeling functional microbial community structure and stress responses in environments at all levels have tremendous implications for our fundamental understanding of hydrobiogeochemical processes and the potential for making bioremediation breakthroughs and illuminating the ‘black box’.

  1. The distinctive biology of cancer in adolescents and young adults.

    Science.gov (United States)

    Bleyer, Archie; Barr, Ronald; Hayes-Lattin, Brandon; Thomas, David; Ellis, Chad; Anderson, Barry

    2008-04-01

    One explanation for the relative lack of progress in treating cancer in adolescents and young adults is that the biology of malignant diseases in this age group is different than in younger and older persons, not only in the spectrum of cancers but also within individual cancer types and within the patient (host). Molecular, epidemiological and therapeutic outcome comparisons offer clues to this distinctiveness in most of the common cancers of adolescents and young adults. Translational and clinical research should not assume that the biology of cancers and patients is the same as in other age groups, and treatment strategies should be tailored to the differences.

  2. A review of imaging techniques for systems biology

    Directory of Open Access Journals (Sweden)

    Po Ming J

    2008-08-01

    Full Text Available Abstract This paper presents a review of imaging techniques and of their utility in system biology. During the last decade systems biology has matured into a distinct field and imaging has been increasingly used to enable the interplay of experimental and theoretical biology. In this review, we describe and compare the roles of microscopy, ultrasound, CT (Computed Tomography, MRI (Magnetic Resonance Imaging, PET (Positron Emission Tomography, and molecular probes such as quantum dots and nanoshells in systems biology. As a unified application area among these different imaging techniques, examples in cancer targeting are highlighted.

  3. Modelling coordination in biological systems

    NARCIS (Netherlands)

    Clarke, D.G.; Oliveira Costa, D.F. de; Arbab, F.

    2004-01-01

    We present an application of the Reo coordination paradigm to provide a compositional formal model for describing and reasoning about the behaviour of biological systems, such as regulatory gene networks. Reo governs the interaction and flow of data between components by allowing the construction of

  4. Tunable promoters in systems biology

    DEFF Research Database (Denmark)

    Mijakovic, Ivan; Petranovic, Dina; Jensen, Peter Ruhdal

    2005-01-01

    The construction of synthetic promoter libraries has represented a major breakthrough in systems biology, enabling the subtle tuning of enzyme activities. A number of tools are now available that allow the modulation of gene expression and the detection of changes in expression patterns. But, how...

  5. Systems Biology of Industrial Microorganisms

    Science.gov (United States)

    Papini, Marta; Salazar, Margarita; Nielsen, Jens

    The field of industrial biotechnology is expanding rapidly as the chemical industry is looking towards more sustainable production of chemicals that can be used as fuels or building blocks for production of solvents and materials. In connection with the development of sustainable bioprocesses, it is a major challenge to design and develop efficient cell factories that can ensure cost efficient conversion of the raw material into the chemical of interest. This is achieved through metabolic engineering, where the metabolism of the cell factory is engineered such that there is an efficient conversion of sugars, the typical raw materials in the fermentation industry, into the desired product. However, engineering of cellular metabolism is often challenging due to the complex regulation that has evolved in connection with adaptation of the different microorganisms to their ecological niches. In order to map these regulatory structures and further de-regulate them, as well as identify ingenious metabolic engineering strategies that full-fill mass balance constraints, tools from systems biology can be applied. This involves both high-throughput analysis tools like transcriptome, proteome and metabolome analysis, as well as the use of mathematical modeling to simulate the phenotypes resulting from the different metabolic engineering strategies. It is in fact expected that systems biology may substantially improve the process of cell factory development, and we therefore propose the term Industrial Systems Biology for how systems biology will enhance the development of industrial biotechnology for sustainable chemical production.

  6. Physical aspects of biological activity and cancer

    Science.gov (United States)

    Pokorný, Jiří

    2012-03-01

    Mitochondria are organelles at the boundary between chemical-genetic and physical processes in living cells. Mitochondria supply energy and provide conditions for physical mechanisms. Protons transferred across the inner mitochondrial membrane diffuse into cytosol and form a zone of a strong static electric field changing water into quasi-elastic medium that loses viscosity damping properties. Mitochondria and microtubules form a unique cooperating system in the cell. Microtubules are electrical polar structures that make possible non-linear transformation of random excitations into coherent oscillations and generation of coherent electrodynamic field. Mitochondria supply energy, may condition non-linear properties and low damping of oscillations. Electrodynamic activity might have essential significance for material transport, organization, intra- and inter-cellular interactions, and information transfer. Physical processes in cancer cell are disturbed due to suppression of oxidative metabolism in mitochodria (Warburg effect). Water ordering level in the cell is decreased, excitation of microtubule electric polar oscilations diminished, damping increased, and non-linear energy transformation shifted towards the linear region. Power and coherence of the generated electrodynamic field are reduced. Electromagnetic activity of healthy and cancer cells may display essential differences. Local invasion and metastastatic growth may strongly depend on disturbed electrodynamic activity. Nanotechnological measurements may disclose yet unknown properties and parameters of electrodynamic oscillations and other physical processes in healthy and cancer cells.

  7. MICA polymorphism: biology and importance in cancer.

    Science.gov (United States)

    Chen, Dan; Gyllensten, Ulf

    2014-12-01

    The major histocompatibility complex class I polypeptide-related sequence A gene (MICA) encodes a membrane-bound protein acting as a ligand to stimulate an activating receptor, NKG2D, expressed on the surface of essentially all human natural killer (NK), γδ T and CD8(+) αβ T cells. MICA protein is absent from most cells but can be induced by infections and oncogenic transformation and is frequently expressed in epithelial tumors. Upon binding to MICA, NKG2D activates cytolytic responses of NK and γδ T cells against infected and tumor cells expressing MICA. Therefore, membrane-bound MICA acts as a signal during the early immune response against infection or spontaneously arising tumors. On the other hand, human tumor cells spontaneously release a soluble form of MICA, causing the downregulation of NKG2D and in turn severe impairment of the antitumor immune response of NK and CD8(+) T cells. This is considered to promote tumor immune evasion and also to compromise host resistance to infections. MICA is the most polymorphic non-classical class I gene. A possible association of MICA polymorphism with genetic predisposition to different cancer types has been investigated in candidate gene-based studies. Two genome-wide association studies have identified loci in MICA that influence susceptibility to cervical neoplasia and hepatitis C virus-induced hepatocellular carcinoma, respectively. Given the current level of interest in the field of MICA gene, we discuss the genetics and biology of the MICA gene and the role of its polymorphism in cancer. Gaps in our understanding and future research needs are also discussed.

  8. Development of a Novel Anti-HIF-1α Screening System Coupled with Biochemical and Biological Validation for Rapidly Selecting Potent Anti-Cancer Compounds.

    Science.gov (United States)

    Lu, Yi; Madu, Chikezie; Masters, Jordan; Lu, Andrew; Li, Liyuan

    2014-01-01

    Breast cancer (BCa) is the most diagnosed cancer and the second leading cause of cancer death in the American women. Adaptation to the hypoxic environment seen in solid tumors is critical for tumor cell survival and growth. The activation of hypoxia inducible factor-1 alpha (HIF-1α), an important master transcriptional factor that is induced and stabilized by intratumoral hypoxia, stimulates a group of HIF-1α-regulated genes including vascular endothelial growth factor (VEGF), leading tumor cells towards malignant progression. Therefore, a promising therapeutic approach to cancer treatment is to target HIF-1α. The goal of this project was to develop and validate a screening system coupled with secondary screen/validation process that has the capability to screen large numbers of potential anti-cancer small-molecule compounds based on their anti-HIF-1α activities. Breast cancer MDA-231 cells were used as the model to select potent anti-HIF-1α compounds by their abilities to inhibit transactivation of a VEGF promoter fused to a luciferase reporter gene under hypoxia. Positive compounds were then validated by a series of assays that confirm compounds' anti-HIF-1α activities including measurement of HIF-1α downstream VEGF gene expression and angiogenic ability of BCa cells. Results of our pilot screening demonstrate that this prototype screening coupled with validation system can effectively select highly potent anti-HIF-1α agents from the compound library, suggesting that this prototype screen system has the potential to be developed into a high-throughput screen (HTS) coupled with automated validation process for the screening and identification of novel and effective anti-cancer drugs based on anti-HIF-1α mechanism.

  9. System biology of gene regulation.

    Science.gov (United States)

    Baitaluk, Michael

    2009-01-01

    ) questions of biological relevance. Thus systems biology could be treated as such a socioscientific phenomenon and a new approach to both experiments and theory that is defined by the strategy of pursuing integration of complex data about the interactions in biological systems from diverse experimental sources using interdisciplinary tools and personnel. PMID:19623486

  10. Robust Design of Biological Circuits: Evolutionary Systems Biology Approach

    OpenAIRE

    Bor-Sen Chen; Chih-Yuan Hsu; Jing-Jia Liou

    2011-01-01

    Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter ...

  11. Systems Biology of the Fluxome

    Directory of Open Access Journals (Sweden)

    Miguel A. Aon

    2015-07-01

    Full Text Available The advent of high throughput -omics has made the accumulation of comprehensive data sets possible, consisting of changes in genes, transcripts, proteins and metabolites. Systems biology-inspired computational methods for translating metabolomics data into fluxomics provide a direct functional, dynamic readout of metabolic networks. When combined with appropriate experimental design, these methods deliver insightful knowledge about cellular function under diverse conditions. The use of computational models accounting for detailed kinetics and regulatory mechanisms allow us to unravel the control and regulatory properties of the fluxome under steady and time-dependent behaviors. This approach extends the analysis of complex systems from description to prediction, including control of complex dynamic behavior ranging from biological rhythms to catastrophic lethal arrhythmias. The powerful quantitative metabolomics-fluxomics approach will help our ability to engineer unicellular and multicellular organisms evolve from trial-and-error to a more predictable process, and from cells to organ and organisms.

  12. Selenium Metabolism in Cancer Cells: The Combined Application of XAS and XFM Techniques to the Problem of Selenium Speciation in Biological Systems

    Directory of Open Access Journals (Sweden)

    Hugh H. Harris

    2013-05-01

    Full Text Available Determining the speciation of selenium in vivo is crucial to understanding the biological activity of this essential element, which is a popular dietary supplement due to its anti-cancer properties. Hyphenated techniques that combine separation and detection methods are traditionally and effectively used in selenium speciation analysis, but require extensive sample preparation that may affect speciation. Synchrotron-based X-ray absorption and fluorescence techniques offer an alternative approach to selenium speciation analysis that requires minimal sample preparation. We present a brief summary of some key HPLC-ICP-MS and ESI-MS/MS studies of the speciation of selenium in cells and rat tissues. We review the results of a top-down approach to selenium speciation in human lung cancer cells that aims to link the speciation and distribution of selenium to its biological activity using a combination of X-ray absorption spectroscopy (XAS and X-ray fluorescence microscopy (XFM. The results of this approach highlight the distinct fates of selenomethionine, methylselenocysteine and selenite in terms of their speciation and distribution within cells: organic selenium metabolites were widely distributed throughout the cells, whereas inorganic selenium metabolites were compartmentalized and associated with copper. New data from the XFM mapping of electrophoretically-separated cell lysates show the distribution of selenium in the proteins of selenomethionine-treated cells. Future applications of this top-down approach are discussed.

  13. Bridging the gaps in systems biology

    OpenAIRE

    Marija Cvijovic; Joachim Almquist; Jonas Hagmar; Stefan Hohmann; Hans\\u2011Michael Kaltenbach; Edda Klipp; Marcus Krantz; Pedro Mendes; Sven Nelander; Jens Nielsen; Andrea Pagnani; Natasa Przulj; Andreas Raue; J\\xf6rg Stelling; Szymon Stoma

    2014-01-01

    International audience Systems biology aims at creating mathematical models, i.e., computational reconstructions of biological systems and processes that will result in a new level of understanding-the elucidation of the basic and presumably conserved "design" and "engineering" principles of biomolecular systems. Thus, systems biology will move biology from a phenomenological to a predictive science. Mathematical modeling of biological networks and processes has already greatly improved ou...

  14. Anion binding in biological systems

    Science.gov (United States)

    Feiters, Martin C.; Meyer-Klaucke, Wolfram; Kostenko, Alexander V.; Soldatov, Alexander V.; Leblanc, Catherine; Michel, Gurvan; Potin, Philippe; Küpper, Frithjof C.; Hollenstein, Kaspar; Locher, Kaspar P.; Bevers, Loes E.; Hagedoorn, Peter-Leon; Hagen, Wilfred R.

    2009-11-01

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L3 (2p3/2) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  15. Anion binding in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Feiters, Martin C [Department of Organic Chemistry, Institute for Molecules and Materials, Faculty of Science, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen (Netherlands); Meyer-Klaucke, Wolfram [EMBL Hamburg Outstation at DESY, Notkestrasse 85, D-22607 Hamburg (Germany); Kostenko, Alexander V; Soldatov, Alexander V [Faculty of Physics, Southern Federal University, Sorge 5, Rostov-na-Donu, 344090 (Russian Federation); Leblanc, Catherine; Michel, Gurvan; Potin, Philippe [Centre National de la Recherche Scientifique and Universite Pierre et Marie Curie Paris-VI, Station Biologique de Roscoff, Place Georges Teissier, BP 74, F-29682 Roscoff cedex, Bretagne (France); Kuepper, Frithjof C [Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban, Argyll PA37 1QA, Scotland (United Kingdom); Hollenstein, Kaspar; Locher, Kaspar P [Institute of Molecular Biology and Biophysics, ETH Zuerich, Schafmattstrasse 20, Zuerich, 8093 (Switzerland); Bevers, Loes E; Hagedoorn, Peter-Leon; Hagen, Wilfred R, E-mail: m.feiters@science.ru.n [Department of Biotechnology, Delft University of Technology, Julianalaan 67, 2628 BC Delft (Netherlands)

    2009-11-15

    We compare aspects of biological X-ray absorption spectroscopy (XAS) studies of cations and anions, and report on some examples of anion binding in biological systems. Brown algae such as Laminaria digitata (oarweed) are effective accumulators of I from seawater, with tissue concentrations exceeding 50 mM, and the vanadate-containing enzyme haloperoxidase is implicated in halide accumulation. We have studied the chemical state of iodine and its biological role in Laminaria at the I K edge, and bromoperoxidase from Ascophyllum nodosum (knotted wrack) at the Br K edge. Mo is essential for many forms of life; W only for certain archaea, such as Archaeoglobus fulgidus and the hyperthermophilic archaeon Pyrococcus furiosus, and some bacteria. The metals are bound and transported as their oxo-anions, molybdate and tungstate, which are similar in size. The transport protein WtpA from P. furiosus binds tungstate more strongly than molybdate, and is related in sequence to Archaeoglobus fulgidus ModA, of which a crystal structure is known. We have measured A. fulgidus ModA with tungstate at the W L{sub 3} (2p{sub 3/2}) edge, and compared the results with the refined crystal structure. XAS studies of anion binding are feasible even if only weak interactions are present, are biologically relevant, and give new insights in the spectroscopy.

  16. Systems Biology as an Integrated Platform for Bioinformatics, Systems Synthetic Biology, and Systems Metabolic Engineering

    OpenAIRE

    Bor-Sen Chen; Chia-Chou Wu

    2013-01-01

    Systems biology aims at achieving a system-level understanding of living organisms and applying this knowledge to various fields such as synthetic biology, metabolic engineering, and medicine. System-level understanding of living organisms can be derived from insight into: (i) system structure and the mechanism of biological networks such as gene regulation, protein interactions, signaling, and metabolic pathways; (ii) system dynamics of biological networks, which provides an understanding of...

  17. Diet & Cancer: An Update for Biology Teachers.

    Science.gov (United States)

    Anastasiou, Clifford J.

    1988-01-01

    Reports on dietary substances which act against cancer-causing agents. Indicates that adapting a lifestyle which combines reduced fat intake with increased fiber-containing foods will reduce the risk of some common cancers. Provides teaching strategies and activities to help students analyze their lifestyles for a reduction in cancer risk. (RT)

  18. The redox biology network in cancer pathophysiology and therapeutics

    Directory of Open Access Journals (Sweden)

    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

  19. Nonlinear dynamics in biological systems

    CERN Document Server

    Carballido-Landeira, Jorge

    2016-01-01

    This book presents recent research results relating to applications of nonlinear dynamics, focusing specifically on four topics of wide interest: heart dynamics, DNA/RNA, cell mobility, and proteins. The book derives from the First BCAM Workshop on Nonlinear Dynamics in Biological Systems, held in June 2014 at the Basque Center of Applied Mathematics (BCAM). At this international meeting, researchers from different but complementary backgrounds, including molecular dynamics, physical chemistry, bio-informatics and biophysics, presented their most recent results and discussed the future direction of their studies using theoretical, mathematical modeling and experimental approaches. Such was the level of interest stimulated that the decision was taken to produce this publication, with the organizers of the event acting as editors. All of the contributing authors are researchers working on diverse biological problems that can be approached using nonlinear dynamics. The book will appeal especially to applied math...

  20. Mutant p53: Multiple Mechanisms Define Biologic Activity in Cancer

    OpenAIRE

    Kim, Michael Paul; Zhang, Yun; Lozano, Guillermina

    2015-01-01

    The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of alterations involve p53 missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may concomitantly gain novel functions, often with deleterious effects. Here, we rev...

  1. Biologic therapies for advanced pancreatic cancer.

    Science.gov (United States)

    He, Aiwu Ruth; Lindenberg, Andreas Peter; Marshall, John Lindsay

    2008-08-01

    Patients with metastatic pancreatic cancer have poor prognosis and short survival due to lack of effective therapy and aggressiveness of the disease. Pancreatic cancer has widespread chromosomal instability, including a high rate of translocations and deletions. Upregulated EGF signaling and mutation of K-RAS are found in most pancreatic cancers. Therefore, inhibitors that target EGF receptor, K-RAS, RAF, MEK, mTOR, VEGF and PDGF, for example, have been evaluated in patients with pancreatic cancer. Although significant activities of these inhibitors have not been observed in the majority of pancreatic cancer patients, an enormous amount of experience and knowledge has been obtained from recent clinical trials. With a better inhibitor or combination of inhibitors, and improvement in the selection of patients for available inhibitors, better therapy for pancreatic cancer is on the horizon.

  2. Ki-67 Proliferation Index in Gastric Cancer - Biologic Significance

    OpenAIRE

    Nabais, C.; Caldeira Fradique, A; Oliveira, M.; Quaresma, L.; Gualdino Silva, J; Vasconcelos, V.; Sacadura, J.; Costa, L; Cabrita, F; Mateus Marques, R; Esteves, J.; Fernandez, G.; Guedes da Silva

    2016-01-01

    Objectives/Introdution: Ki-67 protein has been used as an indicator of proliferation activity in tumor cells. In gastric cancer the prognostic value has not been fully understood. This study was designed to assess the biologic significance of Ki-67 proliferation index (PI) in gastric cancer. Material/Methods: Seventy-two patients with gastric cancer were evaluated. These patients underwent gastric resection, and the tumor tissue was stained immunohistochemically. Ki-67 PI was defi...

  3. [Network structures in biological systems].

    Science.gov (United States)

    Oleskin, A V

    2013-01-01

    Network structures (networks) that have been extensively studied in the humanities are characterized by cohesion, a lack of a central control unit, and predominantly fractal properties. They are contrasted with structures that contain a single centre (hierarchies) as well as with those whose elements predominantly compete with one another (market-type structures). As far as biological systems are concerned, their network structures can be subdivided into a number of types involving different organizational mechanisms. Network organization is characteristic of various structural levels of biological systems ranging from single cells to integrated societies. These networks can be classified into two main subgroups: (i) flat (leaderless) network structures typical of systems that are composed of uniform elements and represent modular organisms or at least possess manifest integral properties and (ii) three-dimensional, partly hierarchical structures characterized by significant individual and/or intergroup (intercaste) differences between their elements. All network structures include an element that performs structural, protective, and communication-promoting functions. By analogy to cell structures, this element is denoted as the matrix of a network structure. The matrix includes a material and an immaterial component. The material component comprises various structures that belong to the whole structure and not to any of its elements per se. The immaterial (ideal) component of the matrix includes social norms and rules regulating network elements' behavior. These behavioral rules can be described in terms of algorithms. Algorithmization enables modeling the behavior of various network structures, particularly of neuron networks and their artificial analogs.

  4. Systems biology of Microbial Communities

    Energy Technology Data Exchange (ETDEWEB)

    Navid, A; Ghim, C; Fenley, A; Yoon, S; Lee, S; Almaas, E

    2008-04-11

    Microbes exist naturally in a wide range of environments, spanning the extremes of high acidity and high temperature to soil and the ocean, in communities where their interactions are significant. We present a practical discussion of three different approaches for modeling microbial communities: rate equations, individual-based modeling, and population dynamics. We illustrate the approaches with detailed examples. Each approach is best fit to different levels of system representation, and they have different needs for detailed biological input. Thus, this set of approaches is able to address the operation and function of microbial communities on a wide range of organizational levels.

  5. Recent advances in lung cancer biology

    Energy Technology Data Exchange (ETDEWEB)

    Lechner, J.

    1995-12-31

    This paper provides an overview of carcinogenesis, especially as related to lung cancers. Various growth factors and their mutated forms as oncogenes are discussed with respect to gene location and their role in the oncogenic process. Finally the data is related to lung cancer induction in uranium miners and exposure to radon.

  6. Systems biology of fungal infection

    Directory of Open Access Journals (Sweden)

    Fabian eHorn

    2012-04-01

    Full Text Available Elucidation of pathogenicity mechanisms of the most important human pathogenic fungi, Aspergillus fumigatus and Candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections.A key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. Because of the high level of complexity, it is necessary to describe and understand invasive fungal infection by taking a systems biological approach, i.e., by a comprehensive quantitative analysis of the non-linear and selective interactions of a large number of functionally diverse, and frequently multifunctional, sets of elements, e.g., genes, proteins, metabolites, which produce coherent and emergent behaviours in time and space. The recent advances in systems biology will now make it possible to uncover the structure and dynamics of molecular and cellular cause-effect relationships within these pathogenic interactions.We review current efforts to integrate omics and image-based data of host-pathogen interactions into network and spatio-temporal models. The modelling will help to elucidate pathogenicity mechanisms and to identify diagnostic biomarkers and potential drug targets for therapy and could thus pave the way for novel intervention strategies based on novel antifungal drugs and cell therapy.

  7. Integrating phosphoproteomics in systems biology

    Directory of Open Access Journals (Sweden)

    Yu Liu

    2014-07-01

    Full Text Available Phosphorylation of serine, threonine and tyrosine plays significant roles in cellular signal transduction and in modifying multiple protein functions. Phosphoproteins are coordinated and regulated by a network of kinases, phosphatases and phospho-binding proteins, which modify the phosphorylation states, recognize unique phosphopeptides, or target proteins for degradation. Detailed and complete information on the structure and dynamics of these networks is required to better understand fundamental mechanisms of cellular processes and diseases. High-throughput technologies have been developed to investigate phosphoproteomes in model organisms and human diseases. Among them, mass spectrometry (MS-based technologies are the major platforms and have been widely applied, which has led to explosive growth of phosphoproteomic data in recent years. New bioinformatics tools are needed to analyze and make sense of these data. Moreover, most research has focused on individual phosphoproteins and kinases. To gain a more complete knowledge of cellular processes, systems biology approaches, including pathways and networks modeling, have to be applied to integrate all components of the phosphorylation machinery, including kinases, phosphatases, their substrates, and phospho-binding proteins. This review presents the latest developments of bioinformatics methods and attempts to apply systems biology to analyze phosphoproteomics data generated by MS-based technologies. Challenges and future directions in this field will be also discussed.

  8. Inflammatory mediators: Parallels between cancer biology and stem cell therapy

    Directory of Open Access Journals (Sweden)

    A Patel

    2009-02-01

    Full Text Available Shyam A Patel1,2,3, Andrew C Heinrich2,3, Bobby Y Reddy2, Pranela Rameshwar21Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 2Department of Medicine – Division of Hematology/Oncology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 3These authors contributed equally to this workAbstract: Inflammation encompasses diverse molecular pathways, and it is intertwined with a wide array of biological processes. Recently, there has been an upsurge of interest in the interactions between mediators of inflammation and other cells such as stem cells and cancer cells. Since tissue injuries are associated with the release of inflammatory mediators, it would be difficult to address this subject without considering the implications of their systemic effects. In this review, we discuss the effects of inflammatory reactions on stem cells and extrapolate on information pertaining to cancer biology. The discussion focuses on integrins and cytokines, and identifies the transcription factor, nuclear factor-kappa B (NFκB as central to the inflammatory response. Since stem cell therapy has been proposed for type II diabetes mellitus, metabolic syndrome, pulmonary edema, these disorders are used as examples to discuss the roles of inflammatory mediators. We propose prospects for future research on targeting the NFκB signaling pathway. Finally, we explore the bridge between inflammation and stem cells, including neural stem cells and adult stem cells from the bone marrow. The implications of mesenchymal stem cells in regenerative medicine as pertaining to inflammation are vast based on their anti-inflammatory and immunosuppressive effects. Such features of stem cells offer great potential for therapy in graft-versus-host disease, conditions with a significant inflammatory component, and tissue regeneration.Keywords: mesenchymal stem cells, cancer, cytokines

  9. Integrative computational biology for cancer research

    OpenAIRE

    Fortney, Kristen; Jurisica, Igor

    2011-01-01

    Over the past two decades, high-throughput (HTP) technologies such as microarrays and mass spectrometry have fundamentally changed clinical cancer research. They have revealed novel molecular markers of cancer subtypes, metastasis, and drug sensitivity and resistance. Some have been translated into the clinic as tools for early disease diagnosis, prognosis, and individualized treatment and response monitoring. Despite these successes, many challenges remain: HTP platforms are often noisy and ...

  10. Analyzing the Biology on the System Level

    Institute of Scientific and Technical Information of China (English)

    Wei Tong

    2004-01-01

    Although various genome projects have provided us enormous static sequence information, understanding of the sophisticated biology continues to require integrating the computational modeling, system analysis, technology development for experiments, and quantitative experiments all together to analyze the biology architecture on various levels, which is just the origin of systems biology subject. This review discusses the object, its characteristics, and research attentions in systems biology, and summarizes the analysis methods, experimental technologies, research developments, and so on in the four key fields of systems biology-systemic structures, dynamics, control methods, and design principles.

  11. Fostering synergy between cell biology and systems biology.

    Science.gov (United States)

    Eddy, James A; Funk, Cory C; Price, Nathan D

    2015-08-01

    In the shared pursuit of elucidating detailed mechanisms of cell function, systems biology presents a natural complement to ongoing efforts in cell biology. Systems biology aims to characterize biological systems through integrated and quantitative modeling of cellular information. The process of model building and analysis provides value through synthesizing and cataloging information about cells and molecules, predicting mechanisms and identifying generalizable themes, generating hypotheses and guiding experimental design, and highlighting knowledge gaps and refining understanding. In turn, incorporating domain expertise and experimental data is crucial for building towards whole cell models. An iterative cycle of interaction between cell and systems biologists advances the goals of both fields and establishes a framework for mechanistic understanding of the genome-to-phenome relationship.

  12. Modeling biological systems with Answer Set Programming

    OpenAIRE

    Thiele, Sven

    2012-01-01

    Biology has made great progress in identifying and measuring the building blocks of life. The availability of high-throughput methods in molecular biology has dramatically accelerated the growth of biological knowledge for various organisms. The advancements in genomic, proteomic and metabolomic technologies allow for constructing complex models of biological systems. An increasing number of biological repositories is available on the web, incorporating thousands of biochemical reactions and ...

  13. Integrating systems biology models and biomedical ontologies

    Directory of Open Access Journals (Sweden)

    de Bono Bernard

    2011-08-01

    Full Text Available Abstract Background Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such an integration of data and are often used to annotate biosimulation models in systems biology. Results We provide a framework to integrate representations of in silico systems biology with those of in vivo biology as described by biomedical ontologies and demonstrate this framework using the Systems Biology Markup Language. We developed the SBML Harvester software that automatically converts annotated SBML models into OWL and we apply our software to those biosimulation models that are contained in the BioModels Database. We utilize the resulting knowledge base for complex biological queries that can bridge levels of granularity, verify models based on the biological phenomenon they represent and provide a means to establish a basic qualitative layer on which to express the semantics of biosimulation models. Conclusions We establish an information flow between biomedical ontologies and biosimulation models and we demonstrate that the integration of annotated biosimulation models and biomedical ontologies enables the verification of models as well as expressive queries. Establishing a bi-directional information flow between systems biology and biomedical ontologies has the potential to enable large-scale analyses of biological systems that span levels of granularity from molecules to organisms.

  14. Principles of Systems Biology, No. 8.

    Science.gov (United States)

    2016-08-01

    Advances in biological engineering headline this month's Cell Systems call (Cell Systems 1, 307), alongside intriguing applications of modeling from the Elf, Goentoro, and Wolf groups. Check out our recent blogpost: http://crosstalk.cell.com/blog/a-call-for-papers-on-biological-engineering-and-synthetic-biology. PMID:27559920

  15. Epidemiology and biology of cervical cancer.

    Science.gov (United States)

    Schoell, W M; Janicek, M F; Mirhashemi, R

    1999-01-01

    Worldwide, cancer of the cervix is the second leading cause of cancer death in women: each year, an estimated 500,000 cases are newly diagnosed. Among populations, there are large differences in incidence rates of invasive cervical cancer: these reflect the influence of environmental factors, screening Papanicolaou (Pap) tests, and treatment of pre-invasive lesions. The high-risk human papillomavirus (HPV) subtypes 16, 18, 31, 33, and 51 have been recovered from more than 95% of cervical cancers. We have made great strides in understanding the molecular mechanism of oncogenesis of this virus, focusing on the action of the E6 and E7 viral oncoproteins. These oncoproteins function by inactivating cell cycle regulators p53 and retinoblastoma (Rb), thus providing the initial event in progression to malignancy. Cervical cancers develop from precursor lesions, which are termed squamous intraepithelial lesions (SIL) and are graded as high or low, depending on the degree of disruption of epithelial differentiation. Viral production occurs in low-grade lesions and is restricted to basal cells. In carcinomas, viral DNA is found integrated into the host genome, but no viral production is seen. The well-defined pre-invasive stages, as well as the viral factors involved at the molecular level, make cervical carcinoma a good model for investigating immune therapeutic alternatives or adjuvants to standard treatments. PMID:10225296

  16. 2. Molecular Biology as a Tool in Cancer Epidemiology

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@There can be little doubt that we are entering a new era in our understanding of the origins of human cancer. Unfortunately from the point of view of the cancer epidemiology community, some of the more recent advances in the molecular biology of cancer (once fully assimilated) will tend to make the talk of the up-to-date cancer epidemiologist a great deal less straightforward than many of us had previously envisaged it to be, There may still be a few cancers that will prove to result from only a few distinctive types of mutation in a relatively small number of genes, but I strongly suspect that the great majority of human cancers that we wish to study will prove to have their origins in a complex set of DNA changes whose precise

  17. Biology of cancer invasion and metastasis.

    Science.gov (United States)

    Mareel, M M; Crombez, R

    1992-01-01

    Current concepts of invasion eventually leading to metastasis are discussed and exemplified by cancers of the head and neck mucosa. Invasion occurs at a number of steps, each step making an ecosystem comprising not only the neoplastic cells but also their normal counterparts, a variety of host cells and the extracellular matrix. The ecosystem concept may explain aspects of metastasis such as site-dependence and organ-specificity of cancer metastasis as well as invasiveness of normal leucocytes. Genes implicated in invasion and metastasis are actively searched for. Recently, the epithelial cell-cell adhesion molecule E-cadherin has been identified as an i- (invasion suppressor) gene product, i.e. a molecule the expression of which counterbalances i+ (invasion promotor) gene activity. Downregulation of E-cadherin in human head and neck cancers may account for their invasive and metastatic behaviour.

  18. Biological Therapy in Treating Patients With Metastatic Cancer

    Science.gov (United States)

    2013-02-21

    Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

  19. Urinary nucleosides as biological markers for patients with colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yu-Fang Zheng; Jun Yang; Xin-Jie Zhao; Bo Feng; Hong-Wei Kong; Ying-Jie Chen; Shen Lv; Min-Hua Zheng; Guo-Wang Xu

    2005-01-01

    AIM: Fourteen urinary nucleosides, primary degradation products of tRNA, were evaluated to know the potential as biological markers for patients with colorectal cancer.METHODS: The concentrations of 14 kinds of urinary nucleosides from 52 patients with colorectal cancer, 10patients with intestinal villous adenoma and 60 healthy adults were determined by column switching high performance liquid chromatography method.RESULTS: The mean levels of 12 kinds of urinary nucleosides (except uridine and guanosine) in the patients with colorectal cancer were significantly higher than those in patients with intestinal villous adenoma or the healthy adults. Using the levels of 14 kinds of urinary nucleosides as the data vectors for principal component analysis, 71% (37/52) patients with colorectal cancer were correctly classified from healthy adults, in which the identification rate was much higher than that of CEA method (29%).Only 10% (1/10) of patients with intestinal villous adenoma were indistinguishable from patients with colorectal cancer. The levels of m1G, Pseu and m1A were positively related with tumor size and Duke's stages of colorectal cancer. When monitoring the changes in urinary nucleoside concentrations of patients with colorectal cancer associated with surgery, it was found that the overall correlations with clinical assessment were 84% (27/32)and 91% (10/11) in response group and progressive group, respectively.CONCLUSION: These findings indicate that urinary nucleosides determined by column switching high performance liquid chromatography method may be useful as biological markers for colorectal cancer.

  20. Applications of dynamical systems in biology and medicine

    CERN Document Server

    Radunskaya, Ami

    2015-01-01

    This volume highlights problems from a range of biological and medical applications that can be interpreted as questions about system behavior or control.  Topics include drug resistance in cancer and malaria, biological fluid dynamics, auto-regulation in the kidney, anti-coagulation therapy, evolutionary diversification and photo-transduction.  Mathematical techniques used to describe and investigate these biological and medical problems include ordinary, partial and stochastic differentiation equations, hybrid discrete-continuous approaches, as well as 2 and 3D numerical simulation. .

  1. Telomere biology: cancer firewall or aging clock?

    Science.gov (United States)

    Mitteldorf, J J

    2013-09-01

    It has been a decade since the first surprising discovery that longer telomeres in humans are statistically associated with longer life expectancies. Since then, it has been firmly established that telomere shortening imposes an individual fitness cost in a number of mammalian species, including humans. But telomere shortening is easily avoided by application of telomerase, an enzyme which is coded into nearly every eukaryotic genome, but whose expression is suppressed most of the time. This raises the question how the sequestration of telomerase might have evolved. The predominant assumption is that in higher organisms, shortening telomeres provide a firewall against tumor growth. A more straightforward interpretation is that telomere attrition provides an aging clock, reliably programming lifespans. The latter hypothesis is routinely rejected by most biologists because the benefit of programmed lifespan applies only to the community, and in fact the individual pays a substantial fitness cost. There is a long-standing skepticism that the concept of fitness can be applied on a communal level, and of group selection in general. But the cancer hypothesis is problematic as well. Animal studies indicate that there is a net fitness cost in sequestration of telomerase, even when cancer risk is lowered. The hypothesis of protection against cancer has never been tested in animals that actually limit telomerase expression, but only in mice, whose lifespans are not telomerase-limited. And human medical evidence suggests a net aggravation of cancer risk from the sequestration of telomerase, because cells with short telomeres are at high risk of neoplastic transformation, and they also secrete cytokines that exacerbate inflammation globally. The aging clock hypothesis fits well with what is known about ancestral origins of telomerase sequestration, and the prejudices concerning group selection are without merit. If telomeres are an aging clock, then telomerase makes an

  2. Spatial Aspects in Biological System Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Resat, Haluk; Costa, Michelle N.; Shankaran, Harish

    2011-01-30

    Mathematical models of the dynamical properties of biological systems aim to improve our understanding of the studied system with the ultimate goal of being able to predict system responses in the absence of experimentation. Despite the enormous advances that have been made in biological modeling and simulation, the inherently multiscale character of biological systems and the stochasticity of biological processes continue to present significant computational and conceptual challenges. Biological systems often consist of well-organized structural hierarchies, which inevitably lead to multiscale problems. This chapter introduces and discusses the advantages and shortcomings of several simulation methods that are being used by the scientific community to investigate the spatio-temporal properties of model biological systems. We first describe the foundations of the methods and then describe their relevance and possible application areas with illustrative examples from our own research. Possible ways to address the encountered computational difficulties are also discussed.

  3. Applicability of Computational Systems Biology in Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning; Hadrup, Niels; Audouze, Karine Marie Laure;

    2014-01-01

    be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method......Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources...... and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search...

  4. Tritium Exchange in Biological Systems

    International Nuclear Information System (INIS)

    Whenever tritium-labelled water is employed as a test solute or tracer in biological systems, an appreciable exchange between tritium and labile hydrogen atoms occurs that frequently affects the nature and interpretation of experimental results. The studies reported here are concerned with the magnitude of the effect that tritium exchange introduces into measurements of total body water and water metabolism in animals and humans. Direct measurements of exchange were made in rats, guinea pigs, pigeons, and rabbits. Tritium-labelled water was administered intravenously or by mouth, and tritium space and turnover determined from the concentration of tritium in blood. The animals were then desiccated to constant weight in vacuo. The specific activity of water collected periodically during desiccation increased by 50% as a result of isotope effects. Water from combustion of dried rabbit tissues contained about 2% of the tritium originally given to the animal. Adipose tissue alone contained little or no exchange tritium. The dried tissues of the other animals were rehydrated with inactive water and the appearance of tritium in the water observed. The specific activity of the water increased in exponential fashion, i.e., 1-exp. (kt), with about 90% of exchange occurring with a half-time of 1 h, and the remaining 10% with a half-time of 10 h. The total tritium extracted accounted for 1.5 to 3.5% of the dose given to the animal, which agrees with the difference between the tritium space and total body water determined by desiccation. An indirect estimate of exchange in humans was derived from concurrent measurements of tritium and antipyrene spaces. The average difference of about 2% in water volume agrees with the direct estimates of exchanges in animals. It is evident that tritium space should be reduced by about 2% to identify it with total body water. The magnitude and relatively slow rate of exchange may also influence the interpretation of metabolic studies with

  5. The biology and clinical development of MEK inhibitors for cancer.

    Science.gov (United States)

    Luke, Jason J; Ott, Patrick A; Shapiro, Geoffrey I

    2014-12-01

    The mitogen-activated protein kinase kinases (MAPKK) MEK1 and MEK2 are integral members of the MAPK/ERK signaling pathway and are of interest in the development of anti-cancer therapeutics. The MAPK/ERK pathway is dysregulated in more than 30 % of cancers, predominately by mutations in RAS and BRAF proteins, and MEK serves as a potential downstream target for both of these. The biology of MEK inhibition is complex, as the molecule is differentially regulated by upstream RAS or RAF. This has impacted on the past development of MEK inhibitors as treatments for cancer and may be exploited in more rational, molecularly selected drug development plans in the future. The role of MEK in cancer and the mechanism of action of MEK inhibitors is reviewed. Furthermore, MEK inhibitors that are available in standard practice, as well as those most advanced in clinical development, are discussed. Finally, next steps in the development of MEK inhibitors are considered.

  6. Current dichotomy between traditional molecular biological and omic research in cancer biology and pharmacology.

    Science.gov (United States)

    Reinhold, William C

    2015-12-10

    There is currently a split within the cancer research community between traditional molecular biological hypothesis-driven and the more recent "omic" forms or research. While the molecular biological approach employs the tried and true single alteration-single response formulations of experimentation, the omic employs broad-based assay or sample collection approaches that generate large volumes of data. How to integrate the benefits of these two approaches in an efficient and productive fashion remains an outstanding issue. Ideally, one would merge the understandability, exactness, simplicity, and testability of the molecular biological approach, with the larger amounts of data, simultaneous consideration of multiple alterations, consideration of genes both of known interest along with the novel, cross-sample comparisons among cell lines and patient samples, and consideration of directed questions while simultaneously gaining exposure to the novel provided by the omic approach. While at the current time integration of the two disciplines remains problematic, attempts to do so are ongoing, and will be necessary for the understanding of the large cell line screens including the Developmental Therapeutics Program's NCI-60, the Broad Institute's Cancer Cell Line Encyclopedia, and the Wellcome Trust Sanger Institute's Cancer Genome Project, as well as the the Cancer Genome Atlas clinical samples project. Going forward there is significant benefit to be had from the integration of the molecular biological and the omic forms or research, with the desired goal being improved translational understanding and application. PMID:26677427

  7. Marine biological data and information management system

    Digital Repository Service at National Institute of Oceanography (India)

    Sarupria, J.S.

    Indian National Oceanographic Data Centre (INODC) is engaged in developing a marine biological data and information management system (BIODIMS). This system will contain the information on zooplankton in the water column, zoobenthic biomass...

  8. AACR centennial series: the biology of cancer metastasis: historical perspective.

    Science.gov (United States)

    Talmadge, James E; Fidler, Isaiah J

    2010-07-15

    Metastasis resistant to therapy is the major cause of death from cancer. Despite almost 200 years of study, the process of tumor metastasis remains controversial. Stephen Paget initially identified the role of host-tumor interactions on the basis of a review of autopsy records. His "seed and soil" hypothesis was substantiated a century later with experimental studies, and numerous reports have confirmed these seminal observations. An improved understanding of the metastatic process and the attributes of the cells selected by this process is critical for the treatment of patients with systemic disease. In many patients, metastasis has occurred by the time of diagnosis, so metastasis prevention may not be relevant. Treating systemic disease and identifying patients with early disease should be our goal. Revitalized research in the past three decades has focused on new discoveries in the biology of metastasis. Even though our understanding of molecular events that regulate metastasis has improved, the contributions and timing of molecular lesion(s) involved in metastasis pathogenesis remain unclear. Review of the history of pioneering observations and discussion of current controversies should increase understanding of the complex and multifactorial interactions between the host and selected tumor cells that contribute to fatal metastasis and should lead to the design of successful therapy.

  9. [Molecular biological predictors for kidney cancer].

    Science.gov (United States)

    Vtorushin, S V; Tarakanova, V O; Zavyalova, M V

    2016-01-01

    The paper considers the data available in the modern literature on studies of potential molecular predictors for renal cell carcinoma (RCC). Investigations of cell death markers, namely; Bcl-2 as an inhibitor of apoptosis, are of interest. Its high expression correlates with a more favorable prognosis. Inactivation of Berclin 1 that is an authophagy indicator in intact tissues gives rise to t high risk for tumorigenesis. At the same time, high Beclin 1 expression in the tissue of the tumor itself results in the lower efficiency of performed chemotherapy. Excess annexin A2 in the tumor promotes the growth and invasion of cancer cells. Patients with tumor over-expression of SAM68 protein involved in cell proliferation have a lower overall survival rate. The lifespan of patients without distinct metastases survive significantly longer in the overexpression of epithelial cell adhesion molecule (EpCAM). High PD-L1 protein expression on the cell membrane is considered to be a potential marker of effective immunotherapy for RCC. PMID:27077146

  10. Genomes, Phylogeny, and Evolutionary Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Medina, Monica

    2005-03-25

    With the completion of the human genome and the growing number of diverse genomes being sequenced, a new age of evolutionary research is currently taking shape. The myriad of technological breakthroughs in biology that are leading to the unification of broad scientific fields such as molecular biology, biochemistry, physics, mathematics and computer science are now known as systems biology. Here I present an overview, with an emphasis on eukaryotes, of how the postgenomics era is adopting comparative approaches that go beyond comparisons among model organisms to shape the nascent field of evolutionary systems biology.

  11. Magellan: a web based system for the integrated analysis of heterogeneous biological data and annotations; application to DNA copy number and expression data in ovarian cancer.

    Science.gov (United States)

    Kingsley, Chris B; Kuo, Wen-Lin; Polikoff, Daniel; Berchuck, Andy; Gray, Joe W; Jain, Ajay N

    2007-02-05

    Recent advances in high throughput biological methods allow researchers to generate enormous amounts of data from a single experiment. In order to extract meaningful conclusions from this tidal wave of data, it will be necessary to develop analytical methods of sufficient power and utility. It is particularly important that biologists themselves be able to perform many of these analyses, such that their background knowledge of the experimental system under study can be used to interpret results and direct further inquiries. We have developed a web-based system, Magellan, which allows the upload, storage, and analysis of multivariate data and textual or numerical annotations. Data and annotations are treated as abstract entities, to maximize the different types of information the system can store and analyze. Annotations can be used in analyses/visualizations, as a means of subsetting data to reduce dimensionality, or as a means of projecting variables from one data type or data set to another. Analytical methods are deployed within Magellan such that new functionalities can be added in a straightforward fashion. Using Magellan, we performed an integrated analysis of genome-wide comparative genomic hybridization (CGH), mRNA expression, and clinical data from ovarian tumors. Analyses included the use of permutation-based methods to identify genes whose mRNA expression levels correlated with patient survival, a nearest neighbor classifier to predict patient survival from CGH data, and curated annotations such as genomic position and derived annotations such as statistical computations to explore the quantitative relationship between CGH and mRNA expression data.

  12. Magellan: A Web Based System for the Integrated Analysis of Heterogeneous Biological Data and Annotations; Application to DNA Copy Number and Expression Data in Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Chris B. Kingsley

    2006-01-01

    Full Text Available Recent advances in high throughput biological methods allow researchers to generate enormous amounts of data from a single experiment. In order to extract meaningful conclusions from this tidal wave of data, it will be necessary to develop analytical methods of sufficient power and utility. It is particularly important that biologists themselves be able to perform many of these analyses, such that their background knowledge of the experimental system under study can be used to interpret results and direct further inquiries. We have developed a web-based system, Magellan, which allows the upload, storage, and analysis of multivariate data and textual or numerical annotations. Data and annotations are treated as abstract entities, to maximize the different types of information the system can store and analyze. Annotations can be used in analyses/visualizations, as a means of subsetting data to reduce dimensionality, or as a means of projecting variables from one data type or data set to another. Analytical methods are deployed within Magellan such that new functionalities can be added in a straightforward fashion. Using Magellan, we performed an integrated analysis of genome-wide comparative genomic hybridization (CGH, mRNA expression, and clinical data from ovarian tumors. Analyses included the use of permutation-based methods to identify genes whose mRNA expression levels correlated with patient survival, a nearest neighbor classifier to predict patient survival from CGH data, and curated annotations such as genomic position and derived annotations such as statistical computations to explore the quantitative relationship between CGH and mRNA expression data.

  13. Skin Cancer: Biology, Risk Factors & Treatment | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Skin Cancer Skin Cancer: Biology, Risk Factors & Treatment Past Issues / Summer 2013 ... Factors When you're told that you have skin cancer, it's natural to wonder what may have caused ...

  14. Multifunctional Delivery Systems for Cancer Gene Therapy

    OpenAIRE

    McErlean, Emma M.; McCrudden, Cian M; McCarthy, Helen O.

    2015-01-01

    This chapter examines key concepts with respect to cancer gene therapy and the current issues with respect to non-viral delivery. The biological and molecular barriers that need to be overcome before effective non-viral delivery systems can be appropriately designed for oncology applications are highlighted and ways to overcome these are discussed. Strategies developed to evade the immune response are also described and targeted gene delivery is examined with the most effective strategies hig...

  15. Systems Medicine: Evolution of Systems Biology From Bench To Bedside

    OpenAIRE

    Wang, Rui-Sheng; Maron, Bradley A.; Loscalzo, Joseph

    2015-01-01

    High-throughput experimental techniques for generating genomes, transcriptomes, proteomes, metabolomes, and interactomes have provided unprecedented opportunities to interrogate biological systems and human diseases on a global level. Systems biology integrates the mass of heterogeneous high-throughput data and predictive computational modeling to understand biological functions as system-level properties. Most human diseases are biological states caused by multiple components of perturbed pa...

  16. Biological control in greenhouse systems.

    Science.gov (United States)

    Paulitz, T C; Bélanger, R R

    2001-01-01

    The controlled environment of greenhouses, the high value of the crops, and the limited number of registered fungicides offer a unique niche for the biological control of plant diseases. During the past ten years, over 80 biocontrol products have been marketed worldwide. A large percentage of these have been developed for greenhouse crops. Products to control soilborne pathogens such as Sclerotinia, Pythium, Rhizoctonia and Fusarium include Coniothyrium minitans, species of Gliocladium, Trichoderma, Streptomyces, and Bacillus, and nonpathogenic Fusarium. Products containing Trichoderma, Ampelomyces quisqualis, Bacillus, and Ulocladium are being developed to control the primary foliar diseases, Botrytis and powdery mildew. The development of Pseudomonas for the control of Pythium diseases in hydroponics and Pseudozyma flocculosa for the control of powdery mildew by two Canadian research programs is presented. In the future, biological control of diseases in greenhouses could predominate over chemical pesticides, in the same way that biological control of greenhouse insects predominates in the United Kingdom. The limitations in formulation, registration, and commercialization are discussed, along with suggested future research priorities. PMID:11701861

  17. Genomes, phylogeny, and evolutionary systems biology

    OpenAIRE

    Medina, Monica

    2005-01-01

    With the completion of the human genome and the growing number of diverse genomes being sequenced, a new age of evolutionary research is currently taking shape. The myriad of technological breakthroughs in biology that are leading to the unification of broad scientific fields such as molecular biology, biochemistry, physics, mathematics, and computer science are now known as systems biology. Here, I present an overview, with an emphasis on eukaryotes, of how the postgenomics era is adopting c...

  18. Developmental systems biology flourishing on new technologies

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Organism development is a systems level process. It has benefited greatly from the recent technological advances in the field of systems biology. DNA microarray, phenome, interactome and transcriptome mapping, the new generation of deep sequencing technologies,and faster and better computational and modeling approaches have opened new frontiers for both systems biologists and developmental biologists to reexamine the old developmental biology questions, such as pattern formation, and to tackle new problems, such as stem cell reprogramming. As showcased in the International Developmental Systems Biology Symposium organized by Chinese Academy of Sciences, developmental systems biology is flourishing in many perspectives, from the evolution of developmental systems, to the underlying genetic and molecular pathways and networks, to the genomic, epigenomic and noncoding levels, to the computational analysis and modeling. We believe that the field will continue to reap rewards into the future with these new approaches.

  19. Developmental systems biology flourishing on new technologies.

    Science.gov (United States)

    Han, Jing-Dong J; Liu, Yi; Xue, Huiling; Xia, Kai; Yu, Hong; Zhu, Shanshan; Chen, Zhang; Zhang, Wei; Huang, Zheng; Jin, Chunyu; Xian, Bo; Li, Jing; Hou, Lei; Han, Yixing; Niu, Chaoqun; Alcon, Timothy C

    2008-10-01

    Organism development is a systems level process. It has benefited greatly from the recent technological advances in the field of systems biology. DNA microarray, phenome, interactome and transcriptome mapping, the new generation of deep sequencing technologies, and faster and better computational and modeling approaches have opened new frontiers for both systems biologists and developmental biologists to reexamine the old developmental biology questions, such as pattern formation, and to tackle new problems, such as stem cell reprogramming. As showcased in the International Developmental Systems Biology Symposium organized by Chinese Academy of Sciences, developmental systems biology is flourishing in many perspectives, from the evolution of developmental systems, to the underlying genetic and molecular pathways and networks, to the genomic, epigenomic and noncoding levels, to the computational analysis and modeling. We believe that the field will continue to reap rewards into the future with these new approaches. PMID:18937914

  20. Applicability of computational systems biology in toxicology.

    Science.gov (United States)

    Kongsbak, Kristine; Hadrup, Niels; Audouze, Karine; Vinggaard, Anne Marie

    2014-07-01

    Systems biology as a research field has emerged within the last few decades. Systems biology, often defined as the antithesis of the reductionist approach, integrates information about individual components of a biological system. In integrative systems biology, large data sets from various sources and databases are used to model and predict effects of chemicals on, for instance, human health. In toxicology, computational systems biology enables identification of important pathways and molecules from large data sets; tasks that can be extremely laborious when performed by a classical literature search. However, computational systems biology offers more advantages than providing a high-throughput literature search; it may form the basis for establishment of hypotheses on potential links between environmental chemicals and human diseases, which would be very difficult to establish experimentally. This is possible due to the existence of comprehensive databases containing information on networks of human protein-protein interactions and protein-disease associations. Experimentally determined targets of the specific chemical of interest can be fed into these networks to obtain additional information that can be used to establish hypotheses on links between the chemical and human diseases. Such information can also be applied for designing more intelligent animal/cell experiments that can test the established hypotheses. Here, we describe how and why to apply an integrative systems biology method in the hypothesis-generating phase of toxicological research.

  1. Establishment and Its Biological Characteristics of Patient-derived Lung Cancer Xenograft Modelse

    Directory of Open Access Journals (Sweden)

    Ying ZHUO

    2010-06-01

    Full Text Available Background and objective With the ongoing need to improve therapy for lung cancer, there has been an increasing interest in the development of reliable preclinical models to test novel therapeutics. The aim of this study is to establish a patient-derived lung cancer xenograft model in mice and to observe the biological characteristics of xenografts. Methods Surgically resectected tumor specimens from patients with lung cancer were implanted in the subcutaneous layer of the NOD/SCID mice. Cancer specimens of percutaneous lung biopsy by CT fluoroscopy were implanted into the subrenal capsule of nude mouse. The subcutaneous carcinoma was surgically removed when it grew to approximately 1.0 cm in diameter, and then re-transplanted into new nude mice. The growth process of transplanted tumor was observed. Expression of CEA, cytokeratin, and Ki67 were detected by immunohistochemistry. Mutations in the exons 18-21 of EGFR and exons 12,59 of K-ras of primary and xenograft tumors were examined. The cell cycle of xenograft tumor cells was analyzed by flow cytometry. Results Eleven cases were conducted for NOD/SCID mice and nude mice modelling. The patient-derived lung cancer xenografts have been established successfully, and the tumor could be passed to new nude mice, including No 2 model (adenocasinoma, No. 3 model (small cell lung cancer, and No. 5 model (squamous cell cancer. High homogeneity was found between xenograft tumors and human lung cancer in histopathology, immunohistochemical phenotype, and EGFR, K-ras mutation status . The S-phase fraction of xenograft cell cycle was prolonged, which indicated that the xenografts remains highly proliferated. Conclusion The xenotransplantation models established for patient-derived lung cancer in immune deficient mice. The success rate is 27%. This model system displayed the biological characteristics of human lung cancer, suggesting that it may provide a stable, reliable, and useful animal model in human

  2. Systems Biology Analysis of Heterocellular Signaling.

    Science.gov (United States)

    Tape, Christopher J

    2016-08-01

    Tissues comprise multiple heterotypic cell types (e.g., epithelial, mesenchymal, and immune cells). Communication between heterotypic cell types is essential for biological cohesion and is frequently dysregulated in disease. Despite the importance of heterocellular communication, most systems biology techniques do not report cell-specific signaling data from mixtures of cells. As a result, our existing perspective of cellular behavior under-represents the influence of heterocellular signaling. Recent technical advances now permit the resolution of systems-level cell-specific signaling data. This review discusses how new physical, spatial, and isotopic resolving methods are facilitating unique systems biology studies of heterocellular communication. PMID:27087613

  3. The Changing Landscape of Breast Cancer: How Biology Drives Therapy

    Directory of Open Access Journals (Sweden)

    Sarah Friend

    2016-01-01

    Full Text Available Breast cancer is the most prevalent life-threatening cancer in women. Optimizing therapy to increase cure rates in early stage disease, and improving life expectancy and palliation for advanced stages, are goals driving major areas of research. The armamentarium of targeted treatments for breast cancer is ever expanding as understanding of breast cancer biology deepens. A revolution in our treatment was heralded a decade ago by the introduction of trastuzumab for human epidermal receptor-2 positive (HER2+ disease resulting in remarkable reductions in recurrence and improvements in overall survival (OS. Advances continue to be made in other breast cancer subtypes targeting key activating pathways for therapeutic development. However, for these other targeted agents, improvement in OS has been elusive. This article focuses on the development of targeted therapy in breast cancer focusing primarily on the last 5 years, to illustrate that as we understand the complex pathways allowing the dysregulated cell to become malignant, it also propels us closer towards the promise of precision and personalized medicine.

  4. State of the art biological therapies in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one ofthe most lethal malignancies with a five-year survivalrate of approximately 5%. Several target agents havebeen tested in PDAC, but almost all have failed todemonstrate efficacy in late phase clinical trials, despitethe better understanding of PDAC molecular biologygenerated by large cancer sequencing initiatives in thepast decade. Eroltinib (a small-molecule tyrosine-kinaseinhibitor of epidermal growth factor receptor) plusgemcitabine is the only schedule with a biological agentapproved for advanced pancreatic cancer, but it hasresulted in a very modest survival benefit in unselectedpatients. In our work, we report a summary of the mainclinical trials (closed and ongoing) that refer to biologicaltherapy evaluation in pancreatic cancer treatment.

  5. A historical discourse analysis of the cancerous and non-cancerous body in secondary biology textbooks

    Science.gov (United States)

    Bowers, Neil Thomas

    This dissertation applies the archeological concepts developed by Michel Foucault to a study of thirteen biology textbooks (1993-2004) in order to develop an understanding of 'purchased truths' concerning cancer. This study focuses on the construction of the health/illness dialogue concerning cancer within the textbooks and not the meaning that the individual makes from reading the text; as such this study concerns itself with social truths rather than the search for an individual awareness of names, dates, or places. This study investigates the practices that allow the creation of dialogues that are inserted into a biology textbook and looks at how discursive formations create the 'truth regime' from which the biology textbook is said to speak. Using the Foucaultian themes of 'event', 'emergence', 'enunciation', and 'exteriority' a new reading of topics concerning cancer emerge from biology textbooks. Cancer is a disease that will impact the lives of countless individuals but coverage devoted to the pathology of cancer in secondary biology textbooks is very limited and no study textbook devoted a whole chapter to the discussion of cancer. There is an identified reduction in the number of pages and depth of coverage devoted to cancer in the newer biology texts compared to the older texts. Humans are pictured more than plants or animals in presentations concerning cancer with emphasis being placed on the digitalization of human cells via the scanning electron microscope. When the whole body is presented it is seldom located within the technology of disease diagnosis and treatment but rather is posed for specific social control. Just as each digitized picture of the cancerous cell in the texts is used to create a story so too are the pictures of the whole body in action. Possible story lines offered by the publishing houses concerning the reaction of the body to cancer are shown to intermingle with risk factor analysis to project a sense of Foucaultian

  6. Biologically based epidemiological studies of electric power and cancer

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, R.G. [Pacific Northwest Lab., Richland, WA (United States)

    1993-12-01

    Use of electricity is a hallmark of the industrialization process, but there has been no suspicion that electricity could increase the risk of cancer. Recently, however, a number of epidemiologic studies have suggested that electromagnetic fields (EMF) may do just that. Although few cancer experiments have been done yet, there are a number of biological effects of EMF reported in the literature that might provide bases for designing cancer experiments and epidemiologic studies. These include effects of EMF on: (a) DNA transcription and translation, (b) calcium balance in cells, and (c) pineal production of melatonin. Alterations in DNA transcription and translation could have pleiotropic effects. Disruption of calcium homeostasis has many implications including oncogene activation, promotional activity via protein kinases and ornithine decarboxylase (ODC), and increasing oxidative stress. Reduction of melatonin suggests a possible increased risk of cancers of hormone-dependent tissues such as breast and prostate. The idea that a cancer-causing agent must either be an initiator or a promoter should be discarded; indeed, the phenomenologic meaning of these two terms has become confused with imputed mechanistic necessity in recent years. Agents that affect division of normal cells or of fully transformed cells can play an important role in clinical cancer development quite apart from initiation or promotion. Epidemiologic studies of EMF and cancer should attempt to take account of other products of electric power (e.g., light at night) or factors associated with occupational EMF exposure (e.g., toxic chemicals) that may increase cancer risk and therefore act as cofactors or confounders. Epidemiology and laboratory studies should act synergistically in determining if there is a problem and identifying mitigation strategies if needed. 84 refs., 3 figs., 1 tab.

  7. Bioferroelectricity and optical properties of biological systems

    Science.gov (United States)

    Bystrov, Vladimir; Bystrova, Natalia

    2003-08-01

    A bioferroelectric approach to analysis of ferroelectric behavior of biological systems is presented. The optical properties of nerve fibers, biomembrane ion channels, and purple membrane films containing bacteriorhodopsin are analyzed. The features, influence of the proton subsystem and proton transfer on the hydrogen-bonded biomolecular structures are analyzed within the ferroelectric liquid-crystal model and possible biomedical applications discussed. The ferroelectric behavior of biological systems and the set of various bioferroelectric effects are considered within the limits of phenomenological theory of ferroelectrics. The nonlinear response to weak actions under conditions critical to human organism is one of specific features characterizing biological objects on molecular, cell and organism levels.

  8. Optimizing systemic therapy for bladder cancer.

    Science.gov (United States)

    Pal, Sumanta K; Milowsky, Matthew I; Plimack, Elizabeth R

    2013-07-01

    Over the past several decades, few new systemic agents have been incorporated into the treatment paradigm for bladder cancer. Platinum-based therapy remains the cornerstone of treatment in the perioperative and metastatic settings. Despite level one evidence, use of cisplatin-based therapy in the neoadjuvant setting has been dismal. Second-line therapy for metastatic disease has only modest activity with no survival benefit. However, the elucidation and investigation of novel molecular targets, new therapeutics, and associated biomarkers with strong biologic rationale are actively changing the landscape in bladder cancer. Although the field is moving rapidly, no new drug approvals are currently pending and a need remains to continue to educate the medical oncology and urology communities on the optimal use of currently available treatments. This article outlines the evidence, including that from prospective studies and meta-analyses, providing the basis for the current recommendations from NCCN, and details previous and ongoing studies of targeted therapy for bladder cancer.

  9. Radiation protection and secondary cancer prevention using biological radioprotectors in radiotherapy

    Directory of Open Access Journals (Sweden)

    Hamid Abdollahi

    2015-09-01

    Full Text Available Radiotherapy is the feasible treatment approach for many malignant diseases and cancers. New radiotherapy techniques such as ion therapy, stereotactic radiosurgery and intensity modulated radiation therapy deliver higher low dose radiation to large volume of normal tissues and are in debating as more secondary cancers inducers. A secondary cancer after radiotherapy is an important issue that reduces treatment efficiency and should be decreased. Radioprotective compounds are of importance in clinical radiation therapy for saving normal tissues. In the present study, we are so interest to introduce, suggest and review the application of biological radioprotectors in radiotherapy. We propose probiotics, prebiotics, gas, vitamin and nanoparticle producing microorganisms as new biological systems based radioprotectors to protect normal tissues. Also, we reviewed the main biological pathways, molecules and also radioadaptive response that act as radioprotectors. In this review we tried to address the secondary cancer induction by radiotherapy and also main biological radiation protection approaches, although there is a wealth of data in this subject.  

  10. Carbon-13 NMR spectroscopy of biological systems

    CERN Document Server

    Beckmann, Nicolau

    1995-01-01

    This book is intended to provide an in-depth understanding of 13C NMR as a tool in biological research. 13C NMR has provided unique information concerning complex biological systems, from proteins and nucleic acids to animals and humans. The subjects addressed include multidimensional heteronuclear techniques for structural studies of molecules in the liquid and solid states, the investigation of interactions in model membranes, the elucidation of metabolic pathwaysin vitro and in vivo on animals, and noninvasive metabolic studies performed on humans. The book is a unique mix of NMR methods and biological applications which makes it a convenient reference for those interested in research in this interdisciplinary area of physics, chemistry, biology, and medicine.Key Features* An interdisciplinary text with emphasis on both 13C NMR methodology and the relevant biological and biomedical issues* State-of-the-art 13C NMR techniques are described; Whenever possible, their advantages over other approaches are empha...

  11. Systems biology: leading the revolution in ecotoxicology.

    Science.gov (United States)

    Garcia-Reyero, Natàlia; Perkins, Edward J

    2011-02-01

    The rapid development of new technologies such as transcriptomics, proteomics, and metabolomics (Omics) are changing the way ecotoxicology is practiced. The data deluge has begun with genomes of over 65 different aquatic species that are currently being sequenced, and many times that number with at least some level of transcriptome sequencing. Integrating these top-down methodologies is an essential task in the field of systems biology. Systems biology is a biology-based interdisciplinary field that focuses on complex interactions in biological systems, with the intent to model and discover emergent properties of the system. Recent studies demonstrate that Omics technologies provide valuable insight into ecotoxicity, both in laboratory exposures with model organisms and with animals exposed in the field. However, these approaches require a context of the whole animal and population to be relevant. Powerful approaches using reverse engineering to determine interacting networks of genes, proteins, or biochemical reactions are uncovering unique responses to toxicants. Modeling efforts in aquatic animals are evolving to interrelate the interacting networks of a system and the flow of information linking these elements. Just as is happening in medicine, systems biology approaches that allow the integration of many different scales of interaction and information are already driving a revolution in understanding the impacts of pollutants on aquatic systems.

  12. TOPICAL REVIEW: Biological and chemical sensors for cancer diagnosis

    Science.gov (United States)

    Simon, Elfriede

    2010-11-01

    The great challenge for sensor systems to be accepted as a relevant diagnostic and therapeutic tool for cancer detection is the ability to determine the presence of relevant biomarkers or biomarker patterns comparably to or even better than the traditional analytical systems. Biosensor and chemical sensor technologies are already used for several clinical applications such as blood glucose or blood gas measurements. However, up to now not many sensors have been developed for cancer-related tests because only a few of the biomarkers have shown clinical relevance and the performance of the sensor systems is not always satisfactory. New genomic and proteomic tools are used to detect new molecular signatures and identify which combinations of biomarkers may detect best the presence or risk of cancer or monitor cancer therapies. These molecular signatures include genetic and epigenetic signatures, changes in gene expressions, protein biomarker profiles and other metabolite profile changes. They provide new changes in using different sensor technologies for cancer detection especially when complex biomarker patterns have to be analyzed. To address requirements for this complex analysis, there have been recent efforts to develop sensor arrays and new solutions (e.g. lab on a chip) in which sampling, preparation, high-throughput analysis and reporting are integrated. The ability of parallelization, miniaturization and the degree of automation are the focus of new developments and will be supported by nanotechnology approaches. This review recaps some scientific considerations about cancer diagnosis and cancer-related biomarkers, relevant biosensor and chemical sensor technologies, their application as cancer sensors and consideration about future challenges.

  13. Tunable promoters in synthetic and systems biology

    DEFF Research Database (Denmark)

    Dehli, Tore; Solem, Christian; Jensen, Peter Ruhdal

    2012-01-01

    in synthetic biology. A number of tools exist to manipulate the steps in between gene sequence and functional protein in living cells, but out of these the most straight-forward approach is to alter the gene expression level by manipulating the promoter sequence. Some of the promoter tuning tools available......Synthetic and systems biologists need standardized, modular and orthogonal tools yielding predictable functions in vivo. In systems biology such tools are needed to quantitatively analyze the behavior of biological systems while the efficient engineering of artificial gene networks is central...... for accomplishing such altered gene expression levels are discussed here along with examples of their use, and ideas for new tools are described. The road ahead looks very promising for synthetic and systems biologists as tools to achieve just about anything in terms of tuning and timing multiple gene expression...

  14. Statistical Model Checking for Biological Systems

    DEFF Research Database (Denmark)

    David, Alexandre; Larsen, Kim Guldstrand; Legay, Axel;

    2014-01-01

    Statistical Model Checking (SMC) is a highly scalable simulation-based verification approach for testing and estimating the probability that a stochastic system satisfies a given linear temporal property. The technique has been applied to (discrete and continuous time) Markov chains, stochastic...... timed automata and most recently hybrid systems using the tool Uppaal SMC. In this paper we enable the application of SMC to complex biological systems, by combining Uppaal SMC with ANIMO, a plugin of the tool Cytoscape used by biologists, as well as with SimBiology®, a plugin of Matlab to simulate...

  15. Spatial Structures and Regulation in Biological Systems

    DEFF Research Database (Denmark)

    Yde, Pernille

    , and the other is the spatial regulation of biological systems, here related to different aspects of the inflammatory response. All systems are studied using computational modelling and mathematical analysis. The first part of the thesis explores different protein aggregation scenarios. In Chapter 1, we consider...

  16. The role of the ALK receptor in cancer biology.

    Science.gov (United States)

    Hallberg, B; Palmer, R H

    2016-09-01

    A vast array of oncogenic variants has been identified for anaplastic lymphoma kinase (ALK). Therefore, there is a need to better understand the role of ALK in cancer biology in order to optimise treatment strategies. This review summarises the latest research on the receptor tyrosine kinase ALK, and how this information can guide the management of patients with cancer that is ALK-positive. A variety of ALK gene alterations have been described across a range of tumour types, including point mutations, deletions and rearrangements. A wide variety of ALK fusions, in which the kinase domain of ALK and the amino-terminal portion of various protein partners are fused, occur in cancer, with echinoderm microtubule-associated protein-like 4 (EML4)-ALK being the most prevalent in non-small-cell lung cancer (NSCLC). Different ALK fusion proteins can mediate different signalling outputs, depending on properties such as subcellular localisation and protein stability. The ALK fusions found in tumours lack spatial and temporal regulation, which can also affect dimerisation and substrate specificity. Two ALK tyrosine kinase inhibitors (TKIs), crizotinib and ceritinib, are currently approved in Europe for use in ALK-positive NSCLC and several others are in development. These ALK TKIs bind slightly differently within the ATP-binding pocket of the ALK kinase domain and are associated with the emergence of different resistance mutation patterns during therapy. This emphasises the need to tailor the sequence of ALK TKIs according to the ALK signature of each patient. Research into the oncogenic functions of ALK, and fast paced development of ALK inhibitors, has substantially improved outcomes for patients with ALK-positive NSCLC. Limited data are available surrounding the physiological ligand-stimulated activation of ALK signalling and further research is needed. Understanding the role of ALK in tumour biology is key to further optimising therapeutic strategies for ALK

  17. [Better understanding of the biology of cancer cells].

    Science.gov (United States)

    Klein, G

    2000-09-25

    Most forms of cancer arise through a Darwinian evolutionary process. The natural selection that ultimately leads to cancer takes place in somatic tissues although it may be triggered by inherited mutations in a small but significant minority. It favors the growth of clones and subclones that are less and less responsive to normal intra- and extracellular growth control mechanisms. The development of molecular biology has led to the identification of many genes that participate in this somatic evolution. They belong to the following groups: Oncogenes, constitutively activated by structural and/or regulatory changes that drive the cell to continuous proliferation; Tumor suppressor genes, that can inhibit the illegitimately activated cell cycle. They contribute to tumor development by loss mutations or permanent down-regulation, e.g. by methylation; Apoptosis inhibitory genes that can contribute to tumor development by raising the apoptotic threshold, and apoptosis promoting genes that can favor the growth of apoptosis prone tumor cells by their loss or inactivation; DNA repair genes whose inactivation can counteract the normal elimination of cells that carry potentially cancer promoting mutations. Inherited mutations in DNA repair genes can lead to familial cancer syndromes. Immortalizing genes that counteract cellular senescence; Angiogenesis promoting genes whose products may stimulate the vascular supply of tumors; Genes whose structural or functional changes may facilitate the escape of tumor cells from immune rejection; The multi-step development of individual tumors can encompass changes in most or all of these genes. They occur independently of each other and without any fixed order or timing. Tumor emancipation from growth control can therefore proceed along various pathways. It follows that each tumor must be regarded as a biologically unique individual.

  18. Sparse combinatorial inference with an application in cancer biology

    OpenAIRE

    Mukherjee, Sach; Pelech, Steven; Neve, Richard M.; Kuo, Wen-Lin; Ziyad, Safiyyah; Spellman, Paul T.; Joe W Gray; Speed, Terence P.

    2008-01-01

    Motivation: Combinatorial effects, in which several variables jointly influence an output or response, play an important role in biological systems. In many settings, Boolean functions provide a natural way to describe such influences. However, biochemical data using which we may wish to characterize such influences are usually subject to much variability. Furthermore, in high-throughput biological settings Boolean relationships of interest are very often sparse, in the sense of being embedde...

  19. Tracking the 2015 Gastrointestinal Cancers Symposium: bridging cancer biology to clinical gastrointestinal oncology

    Directory of Open Access Journals (Sweden)

    Aprile G

    2015-05-01

    Full Text Available Giuseppe Aprile,1 Francesco Leone,2,3 Riccardo Giampieri,4 Mariaelena Casagrande,1 Donatella Marino,2,3 Luca Faloppi,4 Stefano Cascinu,4 Gianpiero Fasola,1 Mario Scartozzi5,6 1Department of Oncology, University and General Hospital, Udine, Italy; 2Medical Oncology Department, University of Turin, 3Institute for Cancer Research and Treatment, Candiolo, Turin, Italy; 4Medical Oncology Unit, Azienda Ospedaliero-Universitaria Ospedali Riuniti, Universita Politecnica delle Marche, Ancona, Italy; 5Medical Oncology Department, University of Cagliari, 6General Hospital, Cagliari, Italy Abstract: The 2015 Gastrointestinal Cancers Symposium (San Francisco, CA, USA; January 15–17 is the world-class conference co-sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the American Gastroenterological Association Institute, and the Society of Surgical Oncology, in which the most innovative research results in digestive tract oncology are presented and discussed. In its twelfth edition, the meeting has provided new insights focusing on the underpinning biology and clinical management of gastrointestinal malignancies. More than 3,400 health care professionals gathered from all over the world to share their experiences on how to bridge the recent novelties in cancer biology with everyday medical practice. In this article, the authors report on the most significant advances, didactically moving on three different anatomic tracks: gastroesophageal malignancies, pancreatic and biliary cancers, and colorectal adenocarcinomas. Keywords: colorectal cancer, gastric cancer, ramucirumab, pembrolizumab, target therapy, onartuzumab, AMG 337

  20. Systems immune monitoring in cancer therapy.

    Science.gov (United States)

    Greenplate, Allison R; Johnson, Douglas B; Ferrell, P Brent; Irish, Jonathan M

    2016-07-01

    Treatments that successfully modulate anti-cancer immunity have significantly improved outcomes for advanced stage malignancies and sparked intense study of the cellular mechanisms governing therapy response and resistance. These responses are governed by an evolving milieu of cancer and immune cell subpopulations that can be a rich source of biomarkers and biological insight, but it is only recently that research tools have developed to comprehensively characterize this level of cellular complexity. Mass cytometry is particularly well suited to tracking cells in complex tissues because >35 measurements can be made on each of hundreds of thousands of cells per sample, allowing all cells detected in a sample to be characterized for cell type, signalling activity, and functional outcome. This review focuses on mass cytometry as an example of systems level characterization of cancer and immune cells in human tissues, including blood, bone marrow, lymph nodes, and primary tumours. This review also discusses the state of the art in single cell tumour immunology, including tissue collection, technical and biological quality controls, computational analysis, and integration of different experimental and clinical data types. Ex vivo analysis of human tumour cells complements both in vivo monitoring, which generally measures far fewer features or lacks single cell resolution, and laboratory models, which incur cell type losses, signalling alterations, and genomic changes during establishment. Mass cytometry is on the leading edge of a new generation of cytomic tools that work with small tissue samples, such as a fine needle aspirates or blood draws, to monitor changes in rare or unexpected cell subsets during cancer therapy. This approach holds great promise for dissecting cellular microenvironments, monitoring how treatments affect tissues, revealing cellular biomarkers and effector mechanisms, and creating new treatments that productively engage the immune system to

  1. Modeling Cancer Metastasis using Global, Quantitative and Integrative Network Biology

    DEFF Research Database (Denmark)

    Schoof, Erwin; Erler, Janine

    cancer networks using Network Biology. Technologies key to this, such as Mass Spectrometry (MS), Next-Generation Sequencing (NGS) and High-Content Screening (HCS) are briefly described. In Chapter II, we cover how signaling networks and mutational data can be modeled in order to gain a better...... number of biological aspects that would need to be understood to enable comprehensive treatment regimens specific to each patient (i.e. personalized medicine). However, in the approaches outlined in this thesis, we chose metastasis as a key process for interrogating the clinical potential of targeting...... 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...

  2. Photosynthetic system as a biological functional element

    International Nuclear Information System (INIS)

    Photosynthetic apparatus of high plants and photosynthetic bacteria is essentially autonomic system in terms of genetics and structural -functional properties located in specific medium, a bio-membrane. Processes of light absorption and exciton migration in light harvesting antenna, separation and further transfer of charges in reaction centers have specific features, which may be used for application of these objects as key elements in construction of future biological functional elements. Progress in study and genetic modification of photosynthetic membranes achieved during the last decade opens great prospects in development biological functional elements and systems. The main characteristics of photosynthetic system for these purposes are: (i) energy conversion processes in the first light phase of the photosynthesis have very short periods, up to picoseconds, which indicates possibility of creation of ultrafast functional elements on their basis; (ii) characteristics sizes of photosynthetic units, 10-100 nm, and possibility to arrange regularly disposed elements in relevant membranes could be prospective point for creation of nano structures and on their basis relevant biologic functional elements; (iii) elements based on modified photosynthetic apparatus and bio-membranes might be efficiently created by methods of gene engineering and manipulation, that open huge opportunities for development of read biological functional systems. In the paper structural-functional properties and characteristics of high plants and purple photosynthetic bacteria, which may be useful for creation of future biological functional elements are considered. (author)

  3. Data driven computing for Biological Systems

    Energy Technology Data Exchange (ETDEWEB)

    Samatova, Nagiza F.; Gorin, Andrey; Uberbacher, Edward; Karpinets, Tatiana V.; Park, Byung H.; Pan, Chongle; Straatsma, TP; Cannon, William R.; Resat, Haluk; Lins, Roberto D.; Oehmen, Christopher S.

    2007-11-01

    Biological breakthroughs that can lead to improved diagnosis and treatment of diseases, generation of clean energy, and solutions to other critical societal problems require high performance, data-intensive computational tools that have the ability to process, analyze and cohesively integrate massive amounts of data and information in real time. Biological computing problems are typically data-intensive and must share very large sets of data effectively across many processors. However, the various components of biological systems, composed of complex networks and pathways, must be integrated to gain a coherent understanding of the system. The more different types of data that can be integrated, the deeper the insights into the biology of the system being studied. Conventional analysis software, however, hasn’t been able to efficiently deal with such massive data set. The goal of the Data-Intensive Computing for Complex Biological Systems (BioPilot) project, a multiyear project funded by the U.S. Department of Energy’s Office of Advanced Scientific Computing Research (ASCR), is to create an integrated suite of highly flexible, highly adaptable pipelines of computational tools for analyzing large-scale data sets that will be used to address specific challenges facing the U.S. Department of Energy (DOE) and our society.

  4. MYC function and regulation in flies: how Drosophila has enlightened MYC cancer biology

    Directory of Open Access Journals (Sweden)

    Jue Er Amanda Lee

    2014-12-01

    Full Text Available Progress in our understanding of the complex signaling events driving human cancer would have been unimaginably slow without discoveries from Drosophila genetic studies. Significantly, many of the signaling pathways now synonymous with cancer biology were first identified as a result of elegant screens for genes fundamental to metazoan development. Indeed the name given to many core cancer-signaling cascades tells of their history as developmental patterning regulators in flies—e.g. Wingless (Wnt, Notch and Hippo. Moreover, astonishing insight has been gained into these complex signaling networks, and many other classic oncogenic signaling networks (e.g. EGFR/RAS/RAF/ERK, InR/PI3K/AKT/TOR, using sophisticated fly genetics. Of course if we are to understand how these signaling pathways drive cancer, we must determine the downstream program(s of gene expression activated to promote the cell and tissue over growth fundamental to cancer. Here we discuss one commonality between each of these pathways: they are all implicated as upstream activators of the highly conserved MYC oncogene and transcription factor. MYC can drive all aspects of cell growth and cell cycle progression during animal development. MYC is estimated to be dysregulated in over 50% of all cancers, underscoring the importance of elucidating the signals activating MYC. We also discuss the FUBP1/FIR/FUSE system, which acts as a ‘cruise control’ on the MYC promoter to control RNA Polymerase II pausing and, therefore, MYC transcription in response to the developmental signaling environment. Importantly, the striking conservation between humans and flies within these major axes of MYC regulation has made Drosophila an extremely valuable model organism for cancer research. We therefore discuss how Drosophila studies have helped determine the validity of signaling pathways regulating MYC in vivo using sophisticated genetics, and continue to provide novel insight into cancer biology.

  5. Stochastic Physics, Complex Systems and Biology

    CERN Document Server

    Qian, Hong

    2012-01-01

    In complex systems, the interplay between nonlinear and stochastic dynamics gives rise to an evolution process in Darwinian sense with punctuated equilibrium, random "mutations" and "adaptations". The emergent discrete states in such a system, i.e., attractors, have natural robustness against both internal and external perturbations. Epigenetic states of a biological cell, a mesoscopic nonlinear stochastic open biochemical system, could be understood through such a framework.

  6. Synthetic biology: advancing biological frontiers by building synthetic systems

    OpenAIRE

    Chen, Yvonne Yu-Hsuan; Galloway, Kate E.; Smolke, Christina D.

    2012-01-01

    Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field.

  7. Systems Biology — the Broader Perspective

    Directory of Open Access Journals (Sweden)

    Jonathan Bard

    2013-06-01

    Full Text Available Systems biology has two general aims: a narrow one, which is to discover how complex networks of proteins work, and a broader one, which is to integrate the molecular and network data with the generation and function of organism phenotypes. Doing all this involves complex methodologies, but underpinning the subject are more general conceptual problems about upwards and downwards causality, complexity and information storage, and their solutions provide the constraints within which these methodologies can be used. This essay considers these general aspects and the particular role of protein networks; their functional outputs are often the processes driving phenotypic change and physiological function—networks are, in a sense, the units of systems biology much as proteins are for molecular biology. It goes on to argue that the natural language for systems-biological descriptions of biological phenomena is the mathematical graph (a set of connected facts of the general form [process] (e.g., [activates] . Such graphs not only integrate events at different levels but emphasize the distributed nature of control as well as displaying a great deal of data. The implications and successes of these ideas for physiology, pharmacology, development and evolution are briefly considered. The paper concludes with some challenges for the future.

  8. Semantic annotation for biological information retrieval system.

    Science.gov (United States)

    Oshaiba, Mohamed Marouf Z; El Houby, Enas M F; Salah, Akram

    2015-01-01

    Online literatures are increasing in a tremendous rate. Biological domain is one of the fast growing domains. Biological researchers face a problem finding what they are searching for effectively and efficiently. The aim of this research is to find documents that contain any combination of biological process and/or molecular function and/or cellular component. This research proposes a framework that helps researchers to retrieve meaningful documents related to their asserted terms based on gene ontology (GO). The system utilizes GO by semantically decomposing it into three subontologies (cellular component, biological process, and molecular function). Researcher has the flexibility to choose searching terms from any combination of the three subontologies. Document annotation is taking a place in this research to create an index of biological terms in documents to speed the searching process. Query expansion is used to infer semantically related terms to asserted terms. It increases the search meaningful results using the term synonyms and term relationships. The system uses a ranking method to order the retrieved documents based on the ranking weights. The proposed system achieves researchers' needs to find documents that fit the asserted terms semantically.

  9. The impact of tumor biology on cancer treatment and multidisciplinary strategies

    Energy Technology Data Exchange (ETDEWEB)

    Molls, Michael [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Vaupel, Peter [University Medical Center, Mainz (Germany). Inst. of Physiology and Pathophysiology; Nieder, Carsten [Nordlandssykehuset HF Hospital, Bodoe (Norway). Dept. of Internal Medicine - Oncology; Anscher, Mitchell S. (eds.) [Virginia Commonwealth University School of Medicine, Richmond, VA (United States). Dept. of Radiation Oncology

    2009-07-01

    This book provides an overview of the fundamentals of tumor biology and the influence of various biologic factors, including inhomogeneity of cancer cells, microenvironment, and host factors, on the design of therapeutic strategies and the outcome of established and emerging treatments. Particular attention is devoted to multidisciplinary combined modality therapy. The topics reviewed include tumorigenesis, cell proliferation, angiogenesis, physiology of malignant tissues, adhesion and invasion, development of metastases, and the role of the immune system in cancer development. Subsequent chapters focus on cancer prevention, detection, and treatment. The principles of chemotherapy, radiotherapy, and molecularly targeted therapy are discussed, treatment resistance is explained, and strategies for rational combinations are provided, including the design of translational studies. Furthermore, the principles and clinical implications of new diagnostic and therapeutic approaches, such as gene expression profiling, gene transfer and silencing, proteomics, and molecular imaging, are presented. The chapters in this book have been written by an outstanding group of basic scientists, clinical researchers, and cancer professionals with long experience in the field. Their aim is to educate and inspire all those who devote most of their work to research into cancer and its treatment. (orig.)

  10. Discovery of Chemical Toxicity via Biological Networks and Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Perkins, Edward; Habib, Tanwir; Guan, Xin; Escalon, Barbara; Falciani, Francesco; Chipman, J.K.; Antczak, Philipp; Edwards, Stephen; Taylor, Ronald C.; Vulpe, Chris; Loguinov, Alexandre; Van Aggelen, Graham; Villeneuve, Daniel L.; Garcia-Reyero, Natalia

    2010-09-30

    Both soldiers and animals are exposed to many chemicals as the result of military activities. Tools are needed to understand the hazards and risks that chemicals and new materials pose to soldiers and the environment. We have investigated the potential of global gene regulatory networks in understanding the impact of chemicals on reproduction. We characterized effects of chemicals on ovaries of the model animal system, the Fathead minnow (Pimopheles promelas) connecting chemical impacts on gene expression to circulating blood levels of the hormones testosterone and estradiol in addition to the egg yolk protein vitellogenin. We describe the application of reverse engineering complex interaction networks from high dimensional gene expression data to characterize chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis that governs reproduction in fathead minnows. The construction of global gene regulatory networks provides deep insights into how drugs and chemicals effect key organs and biological pathways.

  11. Growth Analysis of Cancer Biology Research, 2000-2011

    Directory of Open Access Journals (Sweden)

    Keshava,

    2015-09-01

    Full Text Available Methods and Material: The PubMed database was used for retrieving data on 'cancer biology.' Articles were downloaded from the years 2000 to 2011. The articles were classified chronologically and transferred to a spreadsheet application for analysis of the data as per the objectives of the study. Statistical Method: To investigate the nature of growth of articles via exponential, linear, and logistics tests. Result: The year wise analysis of the growth of articles output shows that for the years 2000 to 2005 and later there is a sudden increase in output, during the years 2006 to 2007 and 2008 to 2011. The high productivity of articles during these years may be due to their significance in cancer biology literature, having received prominence in research. Conclusion: There is an obvious need for better compilations of statistics on numbers of publications in the years from 2000 to 2011 on various disciplines on a worldwide scale, for informed critical assessments of the amount of new knowledge contributed by these publications, and for enhancements and refinements of present Scientometric techniques (citation and publication counts, so that valid measures of knowledge growth may be obtained. Only then will Scientometrics be able to provide accurate, useful descriptions and predictions of knowledge growth.

  12. The new biology of cancer: future clinical applications.

    Science.gov (United States)

    Yarbro, J W

    1989-06-01

    Our recognition that cancer evolves by clonal selection and that the basis for this selection is the growth advantage provided by the inappropriate expression or suppression of genes present in all normal cells allows us to anticipate that the pathways of this evolutionary process may be discovered. If a finite number of such pathways exist with some commonality between various tumors, there is the possibility to anticipate the mechanisms that cell clones might use for both carcinogenesis and tumor progression and to deal with evolving clones before their survival potential becomes overwhelming. As our biochemical understanding increases we may develop the capability to do the following: to identify individuals who have inherited or acquired defective cancer suppressor genes; to identify precursor lesions more exactly; to characterize the degree of progression of a newly diagnosed tumor (has the metastatic phenotype evolved?); to develop antibodies against cell membrane proteins necessary to tumor progression; to produce immune probes that carry cytotoxins or isotopes to specific cell populations; and to take advantage of cell signals to modify tumor growth. The potential for application of the New Biology to cancer medicine seems endless.

  13. Systems Biology for Organotypic Cell Cultures

    Energy Technology Data Exchange (ETDEWEB)

    Grego, Sonia [RTI International, Research Triangle Park, NC (United States); Dougherty, Edward R. [Texas A & M Univ., College Station, TX (United States); Alexander, Francis J. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Auerbach, Scott S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Berridge, Brian R. [GlaxoSmithKline, Research Triangle Park, NC (United States); Bittner, Michael L. [Translational Genomics Research Inst., Phoenix, AZ (United States); Casey, Warren [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Cooley, Philip C. [RTI International, Research Triangle Park, NC (United States); Dash, Ajit [HemoShear Therapeutics, Charlottesville, VA (United States); Ferguson, Stephen S. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Fennell, Timothy R. [RTI International, Research Triangle Park, NC (United States); Hawkins, Brian T. [RTI International, Research Triangle Park, NC (United States); Hickey, Anthony J. [RTI International, Research Triangle Park, NC (United States); Kleensang, Andre [Johns Hopkins Univ., Baltimore, MD (United States). Center for Alternatives to Animal Testing; Liebman, Michael N. [IPQ Analytics, Kennett Square, PA (United States); Martin, Florian [Phillip Morris International, Neuchatel (Switzerland); Maull, Elizabeth A. [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Paragas, Jason [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Qiao, Guilin [Defense Threat Reduction Agency, Ft. Belvoir, VA (United States); Ramaiahgari, Sreenivasa [National Inst. of Environmental Health Sciences, Research Triangle Park, NC (United States); Sumner, Susan J. [RTI International, Research Triangle Park, NC (United States); Yoon, Miyoung [The Hamner Inst. for Health Sciences, Research Triangle Park, NC (United States); ScitoVation, Research Triangle Park, NC (United States)

    2016-08-04

    Translating in vitro biological data into actionable information related to human health holds the potential to improve disease treatment and risk assessment of chemical exposures. While genomics has identified regulatory pathways at the cellular level, translation to the organism level requires a multiscale approach accounting for intra-cellular regulation, inter-cellular interaction, and tissue/organ-level effects. Tissue-level effects can now be probed in vitro thanks to recently developed systems of three-dimensional (3D), multicellular, “organotypic” cell cultures, which mimic functional responses of living tissue. However, there remains a knowledge gap regarding interactions across different biological scales, complicating accurate prediction of health outcomes from molecular/genomic data and tissue responses. Systems biology aims at mathematical modeling of complex, non-linear biological systems. We propose to apply a systems biology approach to achieve a computational representation of tissue-level physiological responses by integrating empirical data derived from organotypic culture systems with computational models of intracellular pathways to better predict human responses. Successful implementation of this integrated approach will provide a powerful tool for faster, more accurate and cost-effective screening of potential toxicants and therapeutics. On September 11, 2015, an interdisciplinary group of scientists, engineers, and clinicians gathered for a workshop in Research Triangle Park, North Carolina, to discuss this ambitious goal. Participants represented laboratory-based and computational modeling approaches to pharmacology and toxicology, as well as the pharmaceutical industry, government, non-profits, and academia. Discussions focused on identifying critical system perturbations to model, the computational tools required, and the experimental approaches best suited to generating key data. This consensus report summarizes the discussions held.

  14. Bridging cancer biology and the patients' needs with nanotechnology-based approaches.

    Science.gov (United States)

    Fonseca, Nuno A; Gregório, Ana C; Valério-Fernandes, Angela; Simões, Sérgio; Moreira, João N

    2014-06-01

    Cancer remains as stressful condition and a leading cause of death in the western world. Actual cornerstone treatments of cancer disease rest as an elusive alternative, offering limited efficacy with extensive secondary effects as a result of severe cytotoxic effects in healthy tissues. The advent of nanotechnology brought the promise to revolutionize many fields including oncology, proposing advanced systems for cancer treatment. Drug delivery systems rest among the most successful examples of nanotechnology. Throughout time they have been able to evolve as a function of an increased understanding from cancer biology and the tumor microenvironment. Marketing of Doxil® unleashed a remarkable impulse in the development of drug delivery systems. Since then, several nanocarriers have been introduced, with aspirations to overrule previous technologies, demonstrating increased therapeutic efficacy besides decreased toxicity. Spatial and temporal targeting to cancer cells has been explored, as well as the use of drug combinations co-encapsulated in the same particle as a mean to take advantage of synergistic interactions in vivo. Importantly, targeted delivery of siRNA for gene silencing therapy has made its way to the clinic for a "first in man" trial using lipid-polymeric-based particles. Focusing in state-of-the-art technology, this review will provide an insightful vision on nanotechnology-based strategies for cancer treatment, approaching them from a tumor biology-driven perspective, since their early EPR-based dawn to the ones that have truly the potential to address unmet medical needs in the field of oncology, upon targeting key cell subpopulations from the tumor microenvironment. PMID:24613464

  15. Modular microfluidic system for biological sample preparation

    Energy Technology Data Exchange (ETDEWEB)

    Rose, Klint A.; Mariella, Jr., Raymond P.; Bailey, Christopher G.; Ness, Kevin Dean

    2015-09-29

    A reconfigurable modular microfluidic system for preparation of a biological sample including a series of reconfigurable modules for automated sample preparation adapted to selectively include a) a microfluidic acoustic focusing filter module, b) a dielectrophoresis bacteria filter module, c) a dielectrophoresis virus filter module, d) an isotachophoresis nucleic acid filter module, e) a lyses module, and f) an isotachophoresis-based nucleic acid filter.

  16. Breast Cancer in Systemic Lupus Erythematosus

    DEFF Research Database (Denmark)

    Tessier Cloutier, B; Clarke, A E; Ramsey-Goldman, R;

    2013-01-01

    Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries.......Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries....

  17. Language Based Techniques for Systems Biology

    DEFF Research Database (Denmark)

    Pilegaard, Henrik

    calculi have similarly been used for the study of bio-chemical reactive systems. In this dissertation it is argued that techniques rooted in the theory and practice of programming languages, language based techniques if you will, constitute a strong basis for the investigation of models of biological......Process calculus is the common denominator for a class of compact, idealised, domain-specific formalisms normally associated with the study of reactive concurrent systems within Computer Science. With the rise of the interactioncentred science of Systems Biology a number of bio-inspired process...... systems as formalised in a process calculus. In particular it is argued that Static Program Analysis provides a useful approach to the study of qualitative properties of such models. In support of this claim a number of static program analyses are developed for Regev’s BioAmbients – a bio-inspired variant...

  18. Systems biology and bioinformatics in aging research: a workshop report.

    Science.gov (United States)

    Fuellen, Georg; Dengjel, Jörn; Hoeflich, Andreas; Hoeijemakers, Jan; Kestler, Hans A; Kowald, Axel; Priebe, Steffen; Rebholz-Schuhmann, Dietrich; Schmeck, Bernd; Schmitz, Ulf; Stolzing, Alexandra; Sühnel, Jürgen; Wuttke, Daniel; Vera, Julio

    2012-12-01

    In an "aging society," health span extension is most important. As in 2010, talks in this series of meetings in Rostock-Warnemünde demonstrated that aging is an apparently very complex process, where computational work is most useful for gaining insights and to find interventions that counter aging and prevent or counteract aging-related diseases. The specific topics of this year's meeting entitled, "RoSyBA: Rostock Symposium on Systems Biology and Bioinformatics in Ageing Research," were primarily related to "Cancer and Aging" and also had a focus on work funded by the German Federal Ministry of Education and Research (BMBF). The next meeting in the series, scheduled for September 20-21, 2013, will focus on the use of ontologies for computational research into aging, stem cells, and cancer. Promoting knowledge formalization is also at the core of the set of proposed action items concluding this report.

  19. Use of biologics and chemotherapy in patients with inflammatory bowel diseases and cancer.

    Science.gov (United States)

    Jauregui-Amezaga, Aranzazu; Vermeire, Séverine; Prenen, Hans

    2016-01-01

    Patients with inflammatory bowel disease have an additional risk of developing cancer compared with the general population. This is due to local chronic inflammation that leads to the development of gastrointestinal cancers and the use of thiopurines, associated with a higher risk of lymphoproliferative disorders, skin cancers, or uterine cervical cancers. Similar to the general population, a previous history of cancer in inflammatory bowel disease patients increases the risk of developing a secondary cancer. Large studies have not shown an increased risk of cancer in patients treated with biologics. In this review we discuss the prevention and treatment of cancer in patients with inflammatory bowel disease. PMID:27065724

  20. Computational systems biology for aging research.

    Science.gov (United States)

    Mc Auley, Mark T; Mooney, Kathleen M

    2015-01-01

    Computational modelling is a key component of systems biology and integrates with the other techniques discussed thus far in this book by utilizing a myriad of data that are being generated to quantitatively represent and simulate biological systems. This chapter will describe what computational modelling involves; the rationale for using it, and the appropriateness of modelling for investigating the aging process. How a model is assembled and the different theoretical frameworks that can be used to build a model are also discussed. In addition, the chapter will describe several models which demonstrate the effectiveness of each computational approach for investigating the constituents of a healthy aging trajectory. Specifically, a number of models will be showcased which focus on the complex age-related disorders associated with unhealthy aging. To conclude, we discuss the future applications of computational systems modelling to aging research.

  1. Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?

    Science.gov (United States)

    Sevimoglu, Tuba; Arga, Kazim Yalcin

    2015-11-01

    Computational biology and 'omics' systems sciences are greatly impacting research on common diseases such as cancer. By contrast, dermatology covering an array of skin diseases with high prevalence in society, has received relatively less attention from 'omics' and computational biosciences. We are focusing on psoriasis, a common and debilitating autoimmune disease involving skin and joints. Using computational systems biology and reconstruction, topological, modular, and a novel correlational analyses (based on fold changes) of biological and transcriptional regulatory networks, we analyzed and integrated data from a total of twelve studies from the Gene Expression Omnibus (sample size = 534). Samples represented a comprehensive continuum from lesional and nonlesional skin, as well as bone marrow and dermal mesenchymal stem cells. We identified and propose here a JAK/STAT signaling pathway significant for psoriasis. Importantly, cytokines, interferon-stimulated genes, antimicrobial peptides, among other proteins, were involved in intrinsic parts of the proposed pathway. Several biomarker and therapeutic candidates such as SUB1 are discussed for future experimental studies. The integrative systems biology approach presented here illustrates a comprehensive perspective on the molecular basis of psoriasis. This also attests to the promise of systems biology research in skin diseases, with psoriasis as a systemic component. The present study reports, to the best of our knowledge, the largest set of microarray datasets on psoriasis, to offer new insights into the disease mechanisms with a proposal of a disease pathway. We call for greater computational systems biology research and analyses in dermatology and skin diseases in general.

  2. Biologic Mechanisms of Oral Cancer Pain and Implications for Clinical Therapy

    OpenAIRE

    Viet, C.T.; SCHMIDT, B.L.

    2012-01-01

    Cancer pain is an ever-present public health concern. With innovations in treatment, cancer patients are surviving longer, but uncontrollable pain creates a poor quality of life for these patients. Oral cancer is unique in that it causes intense pain at the primary site and significantly impairs speech, swallowing, and masticatory functions. We propose that oral cancer pain has underlying biologic mechanisms that are generated within the cancer microenvironment. A comprehensive understanding ...

  3. Mathematical modeling of cancer cell invasion of tissue: biological insight from mathematical analysis and computational simulation.

    Science.gov (United States)

    Andasari, Vivi; Gerisch, Alf; Lolas, Georgios; South, Andrew P; Chaplain, Mark A J

    2011-07-01

    The ability of cancer cells to break out of tissue compartments and invade locally gives solid tumours a defining deadly characteristic. One of the first steps of invasion is the remodelling of the surrounding tissue or extracellular matrix (ECM) and a major part of this process is the over-expression of proteolytic enzymes, such as the urokinase-type plasminogen activator (uPA) and matrix metalloproteinases (MMPs), by the cancer cells to break down ECM proteins. Degradation of the matrix enables the cancer cells to migrate through the tissue and subsequently to spread to secondary sites in the body, a process known as metastasis. In this paper we undertake an analysis of a mathematical model of cancer cell invasion of tissue, or ECM, which focuses on the role of the urokinase plasminogen activation system. The model consists of a system of five reaction-diffusion-taxis partial differential equations describing the interactions between cancer cells, uPA, uPA inhibitors, plasmin and the host tissue. Cancer cells react chemotactically and haptotactically to the spatio-temporal effects of the uPA system. The results obtained from computational simulations carried out on the model equations produce dynamic heterogeneous spatio-temporal solutions and using linear stability analysis we show that this is caused by a taxis-driven instability of a spatially homogeneous steady-state. Finally we consider the biological implications of the model results, draw parallels with clinical samples and laboratory based models of cancer cell invasion using three-dimensional invasion assay, and go on to discuss future development of the model.

  4. Effects of Pesticides on Biological Systems

    Directory of Open Access Journals (Sweden)

    Ergul Belge Kurutas

    2003-06-01

    Full Text Available The use of pesticid both in Turkey and other contries is widespread in order to combat against many pests which cause economical damages. However, pesticides in human pass through skin, respiratory or digestive systems and is metabolized by monooxygenase system dependent upon cytocrome P450 in liver. They also give rise to severe decreases cytochrome P450 and amount of "hem" enzyme activites of glucose-6-phosphatase, pyrophosphatase by stimulating lipid peroxidation on hepatic microsomes. In this study effects of pesticides on biological systems will be presented in genaral terms. [Archives Medical Review Journal 2003; 12(3.000: 215-228

  5. Sodium selenite and cancer related lymphedema: Biological and pharmacological effects.

    Science.gov (United States)

    Pfister, Christina; Dawzcynski, Horst; Schingale, Franz-Josef

    2016-09-01

    A significant percentage of cancer patients develop secondary lymphedema after surgery or radiotherapy. The preferred treatment of secondary lymphedema is complex physical therapy. Pharmacotherapy, for example with diuretics, has received little attention, because they were not effective and only offered short-term solutions. Sodium selenite showed promise as a cost-effective, nontoxic anti-inflammatory agent. Treatment with sodium selenite lowers reactive oxygen species (ROS) production, causes a spontaneous reduction in lymphedema volume, increases the efficacy of physical therapy for lymphedema, and reduces the incidence of erysipelas infections in patients with chronic lymphedema. Besides biological effects in reducing excessive production of ROS, sodium selenite also displays various pharmacological effects. So far the exact mechanisms of these pharmacological effects are mostly unknown, but probably include inhibition of adhesion protein expression. PMID:27267968

  6. A Converter from the Systems Biology Markup Language to the Synthetic Biology Open Language.

    Science.gov (United States)

    Nguyen, Tramy; Roehner, Nicholas; Zundel, Zach; Myers, Chris J

    2016-06-17

    Standards are important to synthetic biology because they enable exchange and reproducibility of genetic designs. This paper describes a procedure for converting between two standards: the Systems Biology Markup Language (SBML) and the Synthetic Biology Open Language (SBOL). SBML is a standard for behavioral models of biological systems at the molecular level. SBOL describes structural and basic qualitative behavioral aspects of a biological design. Converting SBML to SBOL enables a consistent connection between behavioral and structural information for a biological design. The conversion process described in this paper leverages Systems Biology Ontology (SBO) annotations to enable inference of a designs qualitative function. PMID:26696234

  7. Deciphering The Complex Biological Interactions Of Nitric Oxide In Cancer

    Directory of Open Access Journals (Sweden)

    S. Perwez Hussain

    2015-08-01

    Full Text Available NO• is a free radical and is involved in a number of critical physiological processes including vasodilation, neurotransmission, immune regulation and inflammation. There are convincing evidence suggesting a role of NO• in the development and progression of different cancer types. However, the role of NO• in tumorigenesis is highly complex and both pro- and anti-neoplastic functions have been reported, which largely depends on the amount of NO•, cell types, cellular microenvironment, its interaction with other reactive species and presence of metals. An interesting interaction occurs between NO• and p53 tumor suppressor, in which NO•-induced DNA damage causes the stabilization and accumulation of p53, which in turn, transrepresses inducible nitric oxide synthase (NOS2 in a negative feedback loop. In chronic inflammatory diseases, for example ulcerative colitis, NO• induces p53 stabilization and the initiation of DNA-damage response pathway, and also generation of p53 mutation and subsequent clonal selection of p53 mutant cells. Genetic deletion of NOS2 in p53-deficient mice can either suppress or enhance lymphomagenesis depending on the inflammatory microenvironment. These findings highlight the importance of understanding the complex biological interaction of NO• in the context of the molecular makeup of each individual cancer to design NO•-targeted treatment strategies.

  8. Competency development in antibody production in cancer cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Park, M.S.

    1998-12-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The main objective of this project was to develop a rapid recombinant antibody production technology. To achieve the objective, the authors employed (1) production of recombinant antigens that are important for cell cycle regulation and DNA repair, (2) immunization and specific selection of antibody-producing lymphocytes using the flow cytometry and magnetic bead capturing procedure, (3) construction of single chain antibody library, (4) development of recombinant vectors that target, express, and regulate the expression of intracellular antibodies, and (5) specific inhibition of tumor cell growth in tissue culture. The authors have accomplished (1) optimization of a selection procedure to isolate antigen-specific lymphocytes, (2) optimization of the construction of a single-chain antibody library, and (3) development of a new antibody expression vector for intracellular immunization. The future direction of this research is to continue to test the potential use of the intracellular immunization procedure as a tool to study functions of biological molecules and as an immuno-cancer therapy procedure to inhibit the growth of cancer cells.

  9. Computer structures perspective on switching dynamics of simple biological systems

    OpenAIRE

    Moškon, Miha

    2012-01-01

    Synthetic biology is a rapidly evolving discipline that copes with the modifications of existent and with the construction of new biological systems with novel functionalities. Its interdisciplinarity arises from combining of engineering and biological sciences. Biological computing is a relatively new research field that is analyzing the possibilities of constructing a biological computer. Synthetic biology approaches can also be used in order to build biological computer. Certain levels of ...

  10. Graphical Modelling in Genetics and Systems Biology

    OpenAIRE

    Scutari, Marco

    2012-01-01

    Graphical modelling has a long history in statistics as a tool for the analysis of multivariate data, starting from Wright's path analysis and Gibbs' applications to statistical physics at the beginning of the last century. In its modern form, it was pioneered by Lauritzen and Wermuth and Pearl in the 1980s, and has since found applications in fields as diverse as bioinformatics, customer satisfaction surveys and weather forecasts. Genetics and systems biology are unique among these fields in...

  11. Systems Biology from a Yeast Omics Perspective

    OpenAIRE

    Snyder, Michael; Gallagher, Jennifer E.G.

    2009-01-01

    Systems biology represents a paradigm shift from the study of individual genes, proteins or other components to that of the analysis of entire pathways, cellular, developmental, or organismal processes. Large scale studies, primarily initiated in S. cerevisiae, have allowed the identification and characterization of components on an unprecedented level. Large scale interaction, transcription factor binding and phosphorylation data have enabled the elucidation of global regulatory networks. Th...

  12. Book Review of "The Molecular Biology of Cancer" by Stella Pelengaris, Michael Khan (Editors

    Directory of Open Access Journals (Sweden)

    Schmidt Christian

    2007-11-01

    Full Text Available Abstract Here, a review of "The Molecular Biology of Cancer" (Stella Pelengaris and Michael Khan [Editors] is given. The detailed description of the book is provided here: Pelengaris S, Khan M (Eds: The Molecular Biology of Cancer; Blackwell Publishing, Oxford (U.K.; 2006. 531 pages, 214 illustrations, ISBN 9-78140-511-814-9, £31.99.

  13. Effect of small interfering RNA targeting survivin gene on biological behaviour of bladder cancer

    Institute of Scientific and Technical Information of China (English)

    HOU Jian-quan; HE Jun; WANG Xiao-lin; WEN Duan-gai; CHEN Zi-xing

    2006-01-01

    Background Bladder cancer is the most common type of urinary system tumours. It is frequently associated with genetic mutations that deregulate the cell cycle and render these tumours resistant to apoptosis. Survivin, a newly discovered member inhibitor of apoptosis protein (IAP) family in several human cancers, by inducing cell proliferation and inhibiting apoptosis is frequently activated in bladder cancer. We studied the influence of small interfering RNA (siRNA) targeting survivin on the biological behaviour of bladder cancer cells.Methods A double strand survivin target sequence specific siRNA was designed and synthesized. After transfection of bladder cancer cell line T24 by siRNA/liposome complex with increasing concentrations(50-200 nmol/L), the transfectant cells were intratumourally injected at different doses (5 μg or 50μg). The effects were measured in vitro and in vivo.Results The selected siRNA efficiently down-regulated survivin mRNA expression in a dose and time dependent manner. The maximal effect was achieved at the concentration of 100 nmol/L, at which survivin expression level was down-regulated by 75.91%. The inhibition rate of cell growth was 55.29% (P<0.01) and the markedly increased apoptotic rate was 45.70% (P<0.01). In vivo intratumoural injection of 50 μg siRNA-survivin could notably prevent the growth of bladder cancer (P<0.01) in xenografted animals.Conclusion The application of siRNA-survivin could markedly inhibit survivin expression in bladder cancer cell line by inducing apoptosis and inhibiting the growth of the tumour. It may become a new gene therapy tool for bladder cancer.

  14. Potential of biological images for radiation therapy of cancer

    International Nuclear Information System (INIS)

    Full text: Recent technical advances in 3D conformal and intensity modulated radiotherapy (3DCRT and IMRT) based, on patient-specific CT and MRI images, have the potential of delivering exquisitely conformal dose distributions to the target volume while avoiding critical structures. Emerging clinical results in terms of reducing treatment-related morbidity and increasing local control appear promising. Recent developments in imaging have suggested that biological images may further positively impact cancer diagnosis, characterization and therapy. While in the past radiological images are largely anatomical, the new types of images can provide metabolic, biochemical, physiological, functional and molecular (genotypic and phenotypic) information. For radiation therapy, images that give information about factors (e.g. tumor hypoxia, Tpot) that influence radiosensitivity and treatment outcome can be regarded as radiobiological images. The ability of IMRT to 'paint' (in 2D) or 'sculpt' (in 3D) the dose, and produce exquisitely conformal dose distributions begs the '64 million dollar question' as to how to paint or sculpt, and whether biological imaging may provide the pertinent information. Can this new approach provide 'radiobiological phenotypes' non-invasively, and incrementally improve upon the predictive assays of radiobiological characteristics such as proliferative activity (Tpot - the potential doubling time), radiosensitivity (SF2 - the surviving fraction at a dose of 2 Gy), energy status (relative to sublethal damage repair), pH (a possible surrogate of hypoxia), tumor hypoxia, etc. as prognosticator(s) of radiation treatment outcome. Important for IMRT, the spatial (geometrical) distribution of the radiobiological phenotypes provide the basis for dose distribution design to conform to both the physical (geometrical) and the biological attributes. Copyright (2001) Australasian College of Physical Scientists and Engineers in Medicine

  15. Complex biological and bio-inspired systems

    Energy Technology Data Exchange (ETDEWEB)

    Ecke, Robert E [Los Alamos National Laboratory

    2009-01-01

    The understanding and characterization ofthe fundamental processes of the function of biological systems underpins many of the important challenges facing American society, from the pathology of infectious disease and the efficacy ofvaccines, to the development of materials that mimic biological functionality and deliver exceptional and novel structural and dynamic properties. These problems are fundamentally complex, involving many interacting components and poorly understood bio-chemical kinetics. We use the basic science of statistical physics, kinetic theory, cellular bio-chemistry, soft-matter physics, and information science to develop cell level models and explore the use ofbiomimetic materials. This project seeks to determine how cell level processes, such as response to mechanical stresses, chemical constituents and related gradients, and other cell signaling mechanisms, integrate and combine to create a functioning organism. The research focuses on the basic physical processes that take place at different levels ofthe biological organism: the basic role of molecular and chemical interactions are investigated, the dynamics of the DNA-molecule and its phylogenetic role are examined and the regulatory networks of complex biochemical processes are modeled. These efforts may lead to early warning algorithms ofpathogen outbreaks, new bio-sensors to detect hazards from pathomic viruses to chemical contaminants. Other potential applications include the development of efficient bio-fuel alternative-energy processes and the exploration ofnovel materials for energy usages. Finally, we use the notion of 'coarse-graining,' which is a method for averaging over less important degrees of freedom to develop computational models to predict cell function and systems-level response to disease, chemical stress, or biological pathomic agents. This project supports Energy Security, Threat Reduction, and the missions of the DOE Office of Science through its efforts to

  16. Life: An Introduction to Complex Systems Biology

    CERN Document Server

    Kaneko, Kunihiko

    2006-01-01

    What is life? Has molecular biology given us a satisfactory answer to this question? And if not, why, and how to carry on from there? This book examines life not from the reductionist point of view, but rather asks the question: what are the universal properties of living systems and how can one construct from there a phenomenological theory of life that leads naturally to complex processes such as reproductive cellular systems, evolution and differentiation? The presentation has been deliberately kept fairly non-technical so as to address a broad spectrum of students and researchers from the natural sciences and informatics.

  17. [Systems theory in medicine and biology].

    Science.gov (United States)

    Feigl, W; Bonet, E M

    1989-03-15

    We try to determinate, that systems theory has to be introduced into modern medicine. The biological roots as well as the cybernetic ones are outlined. Among various concepts about systems theory the evaluation by Riedl seems to be the most efficient to explain medical procedures. His basic informations refer to von Bertalanffy, the additional introduction of a 4-cause-principle, Aristoteles, permits the explanation of complex relations. The examples of tumor and inflammation are used to demonstrate the basic idea of the formal cause as well as the final cause. The latter should also become an important fact in the solution of other medical problems.

  18. Cancer tissue engineering - new perspectives in understanding the biology of solid tumours - a critical review

    NARCIS (Netherlands)

    Ricci, C.; Moroni, L.; Danti, S.

    2013-01-01

    Understanding cancer biology is a major challenge of this century. The recent insight about carcinogenesis mechanisms, including the role exerted by the tumour microenvironment and cancer stem cells in chemoresistance, relapse and metastases, has made it self-evident that only new cancer models, wit

  19. Study on the biological characteristics of pancreatic cancer vascular endothelial cells

    Institute of Scientific and Technical Information of China (English)

    李雷

    2012-01-01

    Objective To explore the biological characteristics of pancreatic cancer vascular endothelial cells,including the aspects of morphology,species,genetics,vascular formation ability,and proliferation ability in vitro. Methods The human pancreatic cancer cells were inoculated in nude mice pancreas to get pancreatic cancer

  20. Biological role of NK cells and immunotherapeutic approaches in breast cancer

    Directory of Open Access Journals (Sweden)

    María Paula Roberti

    2012-12-01

    Full Text Available In recent decades, tumor surveillance by the immune system and its impact on disease outcomes in cancer patients in general and in breast cancer (BC patients in particular has been documented. Natural killer (NK cells are central components of the innate immunity and existing data indicate that they play a role in preventing and controlling tumor growth and metastasis. Their biological significance was first recognized by their ability to exert direct cellular cytotoxicity without prior sensitization. This is important in tumors, as transforming events are likely to result in downregulation of self-ligands and expression of stress-induced ligands which can be recognized by NK cells. Their activation also leads to secretion of stimulatory cytokines which participate in cancer elimination by several direct mechanisms as well as by stimulating the adaptive immune system. In this regard, it was recently revealed a dendritic cell (DC-NK cell crosstalk which provides another novel pathway linking innate and adaptive immunity. In addition, NK cells are feasible targets of stimulation in immunotherapeutic approaches such as antibody-based strategies and adoptive cell transfer. Nevertheless, NK cells display impaired functionality and capability to infiltrate tumors in BC patients. This review compiles information about NK cell biology in BC and the attempts which aim to manipulate them in novel therapeutic approaches in this pathology.

  1. Diversity-Oriented Synthetic Strategies Applied to Cancer Chemical Biology and Drug Discovery

    OpenAIRE

    Ian Collins; Jones, Alan M.

    2014-01-01

    How can diversity-oriented strategies for chemical synthesis provide chemical tools to help shape our understanding of complex cancer pathways and progress anti-cancer drug discovery efforts? This review (surveying the literature from 2003 to the present) considers the applications of diversity-oriented synthesis (DOS), biology-oriented synthesis (BIOS) and associated strategies to cancer biology and drug discovery, summarising the syntheses of novel and often highly complex scaffolds from p...

  2. Impact of tumor chronology and tumor biology on lymph node metastasis in breast cancer

    OpenAIRE

    Smeets, Ann; Ryckx, Andries; Belmans, Ann; Wildiers, Hans; Neven, Patrick; Floris, Giuseppe; Schöffski, Patrick; Christiaens, Marie-Rose

    2013-01-01

    Synopsis The significance of nodal metastasis in breast cancer is under discussion. We investigated the impact of variables of tumor chronology and tumor biology on the presence of lymph node metastases. Purpose Lymph node involvement is the main prognostic factor in breast cancer. However, it is under discussion whether nodal metastasis in breast cancer only reflects the chronological age of the tumor or whether it is also a marker of tumor biology. The goal of our study was to investigate t...

  3. Engineering biological systems toward a sustainable bioeconomy.

    Science.gov (United States)

    Lopes, Mateus Schreiner Garcez

    2015-06-01

    The nature of our major global risks calls for sustainable innovations to decouple economic growth from greenhouse gases emission. The development of sustainable technologies has been negatively impacted by several factors including sugar production costs, production scale, economic crises, hydraulic fracking development and the market inability to capture externality costs. However, advances in engineering of biological systems allow bridging the gap between exponential growth of knowledge about biology and the creation of sustainable value chains for a broad range of economic sectors. Additionally, industrial symbiosis of different biobased technologies can increase competitiveness and sustainability, leading to the development of eco-industrial parks. Reliable policies for carbon pricing and revenue reinvestments in disruptive technologies and in the deployment of eco-industrial parks could boost the welfare while addressing our major global risks toward the transition from a fossil to a biobased economy.

  4. Engineering biological systems toward a sustainable bioeconomy.

    Science.gov (United States)

    Lopes, Mateus Schreiner Garcez

    2015-06-01

    The nature of our major global risks calls for sustainable innovations to decouple economic growth from greenhouse gases emission. The development of sustainable technologies has been negatively impacted by several factors including sugar production costs, production scale, economic crises, hydraulic fracking development and the market inability to capture externality costs. However, advances in engineering of biological systems allow bridging the gap between exponential growth of knowledge about biology and the creation of sustainable value chains for a broad range of economic sectors. Additionally, industrial symbiosis of different biobased technologies can increase competitiveness and sustainability, leading to the development of eco-industrial parks. Reliable policies for carbon pricing and revenue reinvestments in disruptive technologies and in the deployment of eco-industrial parks could boost the welfare while addressing our major global risks toward the transition from a fossil to a biobased economy. PMID:25845304

  5. Biological Therapy in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Mariana Postal

    2012-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototypic inflammatory autoimmune disorder characterized by multisystem involvement and fluctuating disease activity. Symptoms range from rather mild manifestations such as rash or arthritis to life-threatening end-organ manifestations. Despite new and improved therapy having positively impacted the prognosis of SLE, a subgroup of patients do not respond to conventional therapy. Moreover, the risk of fatal outcomes and the damaging side effects of immunosuppressive therapies in SLE call for an improvement in the current therapeutic management. New therapeutic approaches are focused on B-cell targets, T-cell downregulation and costimulatory blockade, cytokine inhibition, and the modulation of complement. Several biological agents have been developed, but this encouraging news is associated with several disappointments in trials and provide a timely moment to reflect on biologic therapy in SLE.

  6. Adaptable data management for systems biology investigations

    Directory of Open Access Journals (Sweden)

    Burdick David

    2009-03-01

    Full Text Available Abstract Background Within research each experiment is different, the focus changes and the data is generated from a continually evolving barrage of technologies. There is a continual introduction of new techniques whose usage ranges from in-house protocols through to high-throughput instrumentation. To support these requirements data management systems are needed that can be rapidly built and readily adapted for new usage. Results The adaptable data management system discussed is designed to support the seamless mining and analysis of biological experiment data that is commonly used in systems biology (e.g. ChIP-chip, gene expression, proteomics, imaging, flow cytometry. We use different content graphs to represent different views upon the data. These views are designed for different roles: equipment specific views are used to gather instrumentation information; data processing oriented views are provided to enable the rapid development of analysis applications; and research project specific views are used to organize information for individual research experiments. This management system allows for both the rapid introduction of new types of information and the evolution of the knowledge it represents. Conclusion Data management is an important aspect of any research enterprise. It is the foundation on which most applications are built, and must be easily extended to serve new functionality for new scientific areas. We have found that adopting a three-tier architecture for data management, built around distributed standardized content repositories, allows us to rapidly develop new applications to support a diverse user community.

  7. A Free Energy Principle for Biological Systems

    Directory of Open Access Journals (Sweden)

    Friston Karl

    2012-10-01

    Full Text Available This paper describes a free energy principle that tries to explain the ability of biological systems to resist a natural tendency to disorder. It appeals to circular causality of the sort found in synergetic formulations of self-organization (e.g., the slaving principle and models of coupled dynamical systems, using nonlinear Fokker Planck equations. Here, circular causality is induced by separating the states of a random dynamical system into external and internal states, where external states are subject to random fluctuations and internal states are not. This reduces the problem to finding some (deterministic dynamics of the internal states that ensure the system visits a limited number of external states; in other words, the measure of its (random attracting set, or the Shannon entropy of the external states is small. We motivate a solution using a principle of least action based on variational free energy (from statistical physics and establish the conditions under which it is formally equivalent to the information bottleneck method. This approach has proved useful in understanding the functional architecture of the brain. The generality of variational free energy minimisation and corresponding information theoretic formulations may speak to interesting applications beyond the neurosciences; e.g., in molecular or evolutionary biology.

  8. Uncovering the underlying physical mechanisms of biological systems via quantification of landscape and flux

    Science.gov (United States)

    Li, Xu; Xiakun, Chu; Zhiqiang, Yan; Xiliang, Zheng; Kun, Zhang; Feng, Zhang; Han, Yan; Wei, Wu; Jin, Wang

    2016-01-01

    In this review, we explore the physical mechanisms of biological processes such as protein folding and recognition, ligand binding, and systems biology, including cell cycle, stem cell, cancer, evolution, ecology, and neural networks. Our approach is based on the landscape and flux theory for nonequilibrium dynamical systems. This theory provides a unifying principle and foundation for investigating the underlying mechanisms and physical quantification of biological systems. Project supported by the Natural Science Foundation of China (Grant Nos. 21190040, 11174105, 91225114, 91430217, and 11305176) and Jilin Province Youth Foundation, China (Grant No. 20150520082JH).

  9. The Feasibility of Systems Thinking in Biology Education

    Science.gov (United States)

    Boersma, Kerst; Waarlo, Arend Jan; Klaassen, Kees

    2011-01-01

    Systems thinking in biology education is an up and coming research topic, as yet with contrasting feasibility claims. In biology education systems thinking can be understood as thinking backward and forward between concrete biological objects and processes and systems models representing systems theoretical characteristics. Some studies claim that…

  10. Systems Biology: Impressions from a Newcomer Graduate Student in 2016

    Science.gov (United States)

    Simpson, Melanie Rae

    2016-01-01

    As a newcomer, the philosophical basis of systems biology seems intuitive and appealing, the underlying philosophy being that the whole of a living system cannot be completely understood by the study of its individual parts. Yet answers to the questions "What is systems biology?" and "What constitutes a systems biology approach in…

  11. On Mechanical Transitions in Biologically Motivated Soft Matter Systems

    Science.gov (United States)

    Fogle, Craig

    The notion of phase transitions as a characterization of a change in physical properties pervades modern physics. Such abrupt and fundamental changes in the behavior of physical systems are evident in condensed matter system and also occur in nuclear and subatomic settings. While this concept is less prevalent in the field of biology, recent advances have pointed to its relevance in a number of settings. Recent studies have modeled both the cell cycle and cancer as phase transition in physical systems. In this dissertation we construct simplified models for two biological systems. As described by those models, both systems exhibit phase transitions. The first model is inspired by the shape transition in the nuclei of neutrophils during differentiation. During differentiation the nucleus transitions from spherical to a shape often described as "beads on a string." As a simplified model of this system, we investigate the spherical-to-wrinkled transition in an elastic core bounded to a fluid shell system. We find that this model exhibits a first-order phase transition, and the shape that minimizes the energy of the system scales as (micror3/kappa). . The second system studied is motivated by the dynamics of globular proteins. These proteins may undergoes conformational changes with large displacements relative to their size. Transitions between conformational states are not possible if the dynamics are governed strictly by linear elasticity. We construct a model consisting of an predominantly elastic region near the energetic minimum of the system and a non-linear softening of the system at a critical displacement. We find that this simple model displays very rich dynamics include a sharp dynamical phase transition and driving-force-dependent symmetry breaking.

  12. Optimal management of prostate cancer with lethal biology - state-of-the-art local therapy

    Directory of Open Access Journals (Sweden)

    Brian F Chapin

    2015-01-01

    Full Text Available Defining prostate cancer with lethal biology based upon clinical criteria is challenging. Locally advanced/High-Grade prostate cancer can be downstaged or even downgraded with cure in up to 60% of patients with primary therapy. [1] ,[2] ,[3] ,[4] ,[5] However, what is known is that high-grade prostate cancers have a greater potential for recurrence and progression to metastatic disease, which can ultimately result in a patient′s death. Patients with clinical features of "high-risk" prostate cancer (cT2c, PSA >20, ≥ Gl 8 on biopsy are more likely to harbor more aggressive pathologic findings. The optimal management of high-risk prostate cancer is not known as there are not prospective studies comparing surgery to radiation therapy (RT. Retrospective and population-based studies are subject to many biases and attempts to compare surgery and radiation have demonstrated mixed results. Some show equivalent survival outcomes [6] while others showing an advantage of surgery over RT. [7] ,[8] ,[9] ,[10] ,[11] Local therapy for high-risk disease does appear to be beneficial. Improved outcomes realized with local therapy have been clearly demonstrated by several prospective studies evaluating androgen deprivation therapy (ADT alone versus ADT plus RT. The combination of local with systemic treatment showed improved disease-specific and overall survival outcomes. [12], [13], [14] Unfortunately, primary ADT for N0M0 prostate cancer is still inappropriately applied in general practice. [11] While the surgical literature is largely retrospective, it too demonstrates that surgery in the setting of high-risk prostate cancer is effective in providing durable disease-specific and overall survivals. [2] ,[3] ,[15

  13. Optimal management of prostate cancer with lethal biology--state-of-the-art local therapy.

    Science.gov (United States)

    Chapin, Brian F

    2015-01-01

    Defining prostate cancer with lethal biology based upon clinical criteria is challenging. Locally advanced/High-Grade prostate cancer can be downstaged or even downgraded with cure in up to 60% of patients with primary therapy. However, what is known is that high-grade prostate cancers have a greater potential for recurrence and progression to metastatic disease, which can ultimately result in a patient's death. Patients with clinical features of "high-risk" prostate cancer (cT2c, PSA >20, ≥ Gl 8 on biopsy) are more likely to harbor more aggressive pathologic findings. The optimal management of high-risk prostate cancer is not known as there are not prospective studies comparing surgery to radiation therapy (RT). Retrospective and population-based studies are subject to many biases and attempts to compare surgery and radiation have demonstrated mixed results. Some show equivalent survival outcomes while others showing an advantage of surgery over RT. Local therapy for high-risk disease does appear to be beneficial. Improved outcomes realized with local therapy have been clearly demonstrated by several prospective studies evaluating androgen deprivation therapy (ADT) alone versus ADT plus RT. The combination of local with systemic treatment showed improved disease-specific and overall survival outcomes. Unfortunately, primary ADT for N0M0 prostate cancer is still inappropriately applied in general practice. While the surgical literature is largely retrospective, it too demonstrates that surgery in the setting of high-risk prostate cancer is effective in providing durable disease-specific and overall survivals. [ PMID:26178396

  14. The national cancer institute (NCI) and cancer biology in a 'post genome world'

    International Nuclear Information System (INIS)

    The National Cancer Institute (NCI) exists to reduce the burden of all cancers through research and discovery. Extensive restructuring of the NCI over the past year has been aimed at assuring that the institution functions in all ways to promote opportunities for discovery in the laboratory, in the clinic, and in the community. To do this well requires the difficult and almost paradoxical problem of planning for scientific discovery which, in turn is based on the freedom to pursue the unanticipated. The intellectual and structural landscape of science is changing and it places new challenges, new demands and new opportunities for facilitating discovery. The nature of cancer as a disease of genomic instability and of accumulated genetic change, coupled with a possibility of the development of new technologies for reading, utilizing, interpreting and manipulating the genome of single cells, provides unprecedented opportunities for a new type of high through-put biology that will change the nature of discovery, cancer detection, diagnosis, prognosis, therapeutic decision-making and therapeutic discovery. To capture these new opportunities will require attention to be paid to integrate the development of technology and new scientific discoveries with the ability to apply advances rapidly and efficiently through clinical trials

  15. Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer

    OpenAIRE

    Ming Shi; Shan Wang; Yuanfei Yao; Yiqun Li; Hao Zhang; Fang Han; Huan Nie; Jie Su; Zeyu Wang; Lei Yue; Jingyan Cao; Yu Li

    2014-01-01

    Epigenetic silence in cancer frequently altered signal-transduction pathways during the early stages of tumor development. Recent progress in the field of cancer epigenetics has led to new opportunities for diagnosis and treatment of cancer. We previously demonstrated that novel identified nuclear factor MARVELD1 was widely expressed in human tissues, but down-regulated by promoter methylation in multiple cancers. This study was carried out to determine the biological and clinical significanc...

  16. Dielectric relaxation in biological systems physical principles, methods, and applications

    CERN Document Server

    Feldman, Yuri

    2015-01-01

    This title covers the theoretical basis and practical aspects of the study of dielectric properties of biological systems, such as water, electrolyte and polyelectrolytes, solutions of biological macromolecules, cells suspensions and cellular systems.

  17. Redefining plant systems biology: from cell to ecosystem

    NARCIS (Netherlands)

    Keurentjes, J.J.B.; Angenent, G.C.; Dicke, M.; Martins Dos Santos, V.A.P.; Molenaar, J.; Putten, van der W.H.; Ruiter, de P.C.; Struik, P.C.; Thomma, B.

    2011-01-01

    Molecular biologists typically restrict systems biology to cellular levels. By contrast, ecologists define biological systems as communities of interacting individuals at different trophic levels that process energy, nutrient and information flows. Modern plant breeding needs to increase agricultura

  18. Model checking biological systems described using ambient calculus

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Priami, Corrado; Qualia, Paola;

    2005-01-01

    Model checking biological systems described using ambient calculus. In Proc. of the second International Workshop on Computational Methods in Systems Biology (CMSB04), Lecture Notes in Bioinformatics 3082:85-103, Springer, 2005....

  19. Physical Activity and Gastrointestinal Cancers: Primary and Tertiary Preventive Effects and Possible Biological Mechanisms

    Directory of Open Access Journals (Sweden)

    Karen Steindorf

    2015-07-01

    Full Text Available Gastrointestinal cancers account for 37% of all cancer deaths worldwide, underlining the need to further investigate modifiable factors for gastrointestinal cancer risk and prognosis. This review summarizes the corresponding evidence for physical activity (PA, including, briefly, possible biological mechanisms. Despite high public health relevance, there is still a scarcity of studies, especially for tertiary prevention. Besides the convincing evidence of beneficial effects of PA on colon cancer risk, clear risk reduction for gastroesophageal cancer was identified, as well as weak indications for pancreatic cancer. Inverse associations were observed for liver cancer, yet based on few studies. Only for rectal cancer, PA appeared to be not associated with cancer risk. With regard to cancer-specific mortality of the general population, published data were rare but indicated suggestive evidence of protective effects for colon and liver cancer, and to a lesser extent for rectal and gastroesophageal cancer. Studies in cancer patients on cancer-specific and total mortality were published for colorectal cancer only, providing good evidence of inverse associations with post-diagnosis PA. Overall, evidence of associations of PA with gastrointestinal cancer risk and progression is promising but still limited. However, the already available knowledge further underlines the importance of PA to combat cancer.

  20. Molecular Biology of Pancreatic Cancer: How Useful Is It in Clinical Practice?

    Directory of Open Access Journals (Sweden)

    George H Sakorafas

    2012-07-01

    Full Text Available Context During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. Objective To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Methods Reports about clinical implications of molecular biology in patients with pancreatic cancer were retrieved from PubMed. These reports were selected on the basis of their clinical relevance, and the data of their publication (preferentially within the last 5 years. Emphasis was placed on reports investigating diagnostic, prognostic, and therapeutic implications. Results Molecular biology can be used to identify individuals at high-risk for pancreatic cancer development. Intensive surveillance is indicated in these patients to detect pancreatic neoplasia ideally at a preinvasive stage, when curative resection is still possible. Molecular biology can also be used in the diagnosis of pancreatic cancer, with molecular analysis on samples of biologic material, such as serum or plasma, duodenal fluid or preferentially pure pancreatic juice, pancreatic cells or tissue, and stools. Molecular indices have also prognostic significance. Finally, molecular biology may have therapeutic implications by using various therapeutic approaches, such as antiangiogenic factors, purine synthesis inhibitors, matrix metalloproteinase inhibitors, factors modulating tumor-stroma interaction, inactivation of the hedgehog pathway, gene therapy, oncolytic viral therapy, immunotherapy (both passive as well as active etc. Conclusion Molecular biology may have important clinical implications in patients with pancreatic cancer and represents one of the most active areas on cancer research. Hopefully clinical applications of molecular biology

  1. AN INTEGRATED BIOLOGICAL CONTROL SYSTEM AT HANFORD

    Energy Technology Data Exchange (ETDEWEB)

    JOHNSON AR; CAUDILL JG; GIDDINGS RF; RODRIGUEZ JM; ROOS RC; WILDE JW

    2010-02-11

    In 1999 an integrated biological control system was instituted at the U.S. Department of Energy's Hanford Site. Successes and changes to the program needed to be communicated to a large and diverse mix of organizations and individuals. Efforts at communication are directed toward the following: Hanford Contractors (Liquid or Tank Waste, Solid Waste, Environmental Restoration, Science and Technology, Site Infrastructure), General Hanford Employees, and Hanford Advisory Board (Native American Tribes, Environmental Groups, Local Citizens, Washington State and Oregon State regulatory agencies). Communication was done through direct interface meetings, individual communication, where appropriate, and broadly sharing program reports. The objectives of the communication efforts was to have the program well coordinated with Hanford contractors, and to have the program understood well enough that all stakeholders would have confidence in the work performed by the program to reduce or elimated spread of radioactive contamination by biotic vectors. Communication of successes and changes to an integrated biological control system instituted in 1999 at the Department of Energy's Hanford Site have required regular interfaces with not only a diverse group of Hanford contractors (i.e., those responsible for liquid or tank waste, solid wastes, environmental restoration, science and technology, and site infrastructure), and general Hanford employees, but also with a consortium of designated stake holders organized as the Hanford Advisory Board (i.e., Native American tribes, various environmental groups, local citizens, Washington state and Oregon regulatory agencies, etc.). Direct interface meetings, individual communication where appropriate, and transparency of the biological control program were the methods and outcome of this effort.

  2. An Integrated Biological Control System At Hanford

    International Nuclear Information System (INIS)

    In 1999 an integrated biological control system was instituted at the U.S. Department of Energy's Hanford Site. Successes and changes to the program needed to be communicated to a large and diverse mix of organizations and individuals. Efforts at communication are directed toward the following: Hanford Contractors (Liquid or Tank Waste, Solid Waste, Environmental Restoration, Science and Technology, Site Infrastructure), General Hanford Employees, and Hanford Advisory Board (Native American Tribes, Environmental Groups, Local Citizens, Washington State and Oregon State regulatory agencies). Communication was done through direct interface meetings, individual communication, where appropriate, and broadly sharing program reports. The objectives of the communication efforts was to have the program well coordinated with Hanford contractors, and to have the program understood well enough that all stakeholders would have confidence in the work performed by the program to reduce or elimate spread of radioactive contamination by biotic vectors. Communication of successes and changes to an integrated biological control system instituted in 1999 at the Department of Energy's Hanford Site have required regular interfaces with not only a diverse group of Hanford contractors (i.e., those responsible for liquid or tank waste, solid wastes, environmental restoration, science and technology, and site infrastructure), and general Hanford employees, but also with a consortium of designated stake holders organized as the Hanford Advisory Board (i.e., Native American tribes, various environmental groups, local citizens, Washington state and Oregon regulatory agencies, etc.). Direct interface meetings, individual communication where appropriate, and transparency of the biological control program were the methods and outcome of this effort.

  3. Natural Killer Cells: Biology and Clinical Use in Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    William H. D. Hallett; William J. Murphy

    2004-01-01

    Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment, as well as the ability to elicit potent anti-tumor effects. However the clinical results for these processes are still elusive. Greater understanding of NK cell biology, from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation, needs to be appreciated in order to draw out the clinical potential of NK cells. Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many potential ligands. The modulation of activating and inhibitory receptors may hold the key to clinical success involving NK cells. Pre-clinical studies in mice have shown that different combinations of activating and inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD), promote engraftment, and provide superior graft-versus-tumor (GVT) responses. Recent clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of relapse. This review will attempt to be a synthesis of current knowledge concerning NK cells, their involvement in BMT, and their use as an immunotherapy for cancer and other hematologic malignancies. Cellular & Molecular Immunology. 2004;1(1):12-21.

  4. Natural Killer Cells: Biology and Clinical Use in Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    WilliamH.D.Hallett; WilliamJ.Murphy

    2004-01-01

    Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment, as well as the ability to elicit potent anti-tumor effects. However the clinical results for these processes are still elusive. Greater understanding of NK cell biology, from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation, needs to be appreciated in order to draw out the clinical potential of NK cells. Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many potential ligands. The modulation of activating and inhibitory receptors may hold the key to clinical success involving NK cells. Pre-clinical studies in mice have shown that different combinations of activating and inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD), promote engraftment, and provide superior graft-versus-tumor (GVT) responses. Recent clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of relapse. This review will attempt to be a synthesis of current knowledge concerning NK cells, their involvement in BMT, and their use as an immunotherapy for cancer and other hematologic malignancies. Cellular & Molecular Immunology. 2004;1(1):12-21.

  5. Non-Equilibrium Quantum Entanglement in Biological Systems

    Institute of Scientific and Technical Information of China (English)

    LI Hong-Rong; ZHANG Pei; GAO Hong; BI Wen-Ting; ALAMRI M. D.; LI Fu-Li

    2012-01-01

    A non-equilibrium model of a classically driven quantum harmonic oscillator is proposed to explain persistent quantum entanglement in biological systems at ambient temperature. The conditions for periodic entanglement generation are derived. Our results support the evidence that biological systems may have quantum entanglement at biological temperatures.%A non-equilibrium model of a classically driven quantum harmonic oscillator is proposed to explain persistent quantum entanglement in biological systems at ambient temperature.The conditions for periodic entanglement generation are derived.Our results support the evidence that biological systems may have quantum entanglement at biological temperatures.

  6. Stochastic transport processes in discrete biological systems

    CERN Document Server

    Frehland, Eckart

    1982-01-01

    These notes are in part based on a course for advanced students in the applications of stochastic processes held in 1978 at the University of Konstanz. These notes contain the results of re­ cent studies on the stochastic description of ion transport through biological membranes. In particular, they serve as an introduction to an unified theory of fluctuations in complex biological transport systems. We emphasize that the subject of this volume is not to introduce the mathematics of stochastic processes but to present a field of theoretical biophysics in which stochastic methods are important. In the last years the study of membrane noise has become an important method in biophysics. Valuable information on the ion transport mechanisms in membranes can be obtained from noise analysis. A number of different processes such as the opening and closing of ion channels have been shown to be sources of the measured current or voltage fluctuations. Bio­ logical 'transport systems can be complex. For example, the tr...

  7. Biological Systems for Hydrogen Photoproduction (Presentation)

    Energy Technology Data Exchange (ETDEWEB)

    Ghirardi, M. L.

    2012-05-01

    This presentation summarizes NREL biological systems for hydrogen photoproduction work for the DOE Hydrogen and Fuel Cells Program Annual Merit Review and Peer Evaluation Meeting, May 14-18, 2012. General goal is develop photobiological systems for large-scale, low cost and efficient H{sub 2} production from water (barriers AH, AI and AJ). Specific tasks are: (1) Address the O{sub 2} sensitivity of hydrogenases that prevent continuity of H{sub 2} photoproduction under aerobic, high solar-to-hydrogen (STH) light conversion efficiency conditions; and (2) Utilize a limited STH H{sub 2}-producing method (sulfur deprivation) as a platform to address or test other factors limiting commercial algal H{sub 2} photoproduction, including low rates due to biochemical and engineering mechanisms.

  8. Are Biological Systems Poised at Criticality?

    Science.gov (United States)

    Mora, Thierry; Bialek, William

    2011-07-01

    Many of life's most fascinating phenomena emerge from interactions among many elements—many amino acids determine the structure of a single protein, many genes determine the fate of a cell, many neurons are involved in shaping our thoughts and memories. Physicists have long hoped that these collective behaviors could be described using the ideas and methods of statistical mechanics. In the past few years, new, larger scale experiments have made it possible to construct statistical mechanics models of biological systems directly from real data. We review the surprising successes of this "inverse" approach, using examples from families of proteins, networks of neurons, and flocks of birds. Remarkably, in all these cases the models that emerge from the data are poised near a very special point in their parameter space—a critical point. This suggests there may be some deeper theoretical principle behind the behavior of these diverse systems.

  9. Strategies for structuring interdisciplinary education in Systems Biology

    DEFF Research Database (Denmark)

    Cvijovic, Marija; Höfer, Thomas; Aćimović, Jure;

    2016-01-01

    Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological fu...

  10. Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance

    Directory of Open Access Journals (Sweden)

    Dimitrios Mougiakakos

    2011-03-01

    Full Text Available Regulatory T cells (Tregs were initially described as "suppressive" lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.

  11. Regulatory T Cells in Colorectal Cancer: From Biology to Prognostic Relevance

    Energy Technology Data Exchange (ETDEWEB)

    Mougiakakos, Dimitrios [Department of Oncology and Pathology, Immune and Gene Therapy Unit, Cancer Centre Karolinska, CCK R8:01, 17176 Stockholm (Sweden)

    2011-03-29

    Regulatory T cells (Tregs) were initially described as “suppressive” lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.

  12. The biological significance and clinical applications of exosomes in ovarian cancer.

    Science.gov (United States)

    Dorayappan, Kalpana Deepa Priya; Wallbillich, John J; Cohn, David E; Selvendiran, Karuppaiyah

    2016-07-01

    Exosomes are nano-sized (20-100nm) vesicles released by a variety of cells and are generated within the endosomal system or at the plasma membrane. There is emerging evidence that exosomes play a key role in intercellular communication in ovarian and other cancers. The protein and microRNA content of exosomes has been implicated in various intracellular processes that mediate oncogenesis, tumor spread, and drug resistance. Exosomes may prime distant tissue sites for reception of future metastases and their release can be mediated by the tumor microenvironment (e.g., hypoxia). Ovarian cancer-derived exosomes have unique features that could be leveraged for use as biomarkers to facilitate improved detection and treatment of the disease. Further, exosomes have the potential to serve as targets and/or drug delivery vehicles in the treatment of ovarian cancer. In this review we discuss the biological and clinical significance of exosomes relevant to the progression, detection, and treatment of ovarian cancer. PMID:27058839

  13. Systems biology for molecular life sciences and its impact in biomedicine.

    Science.gov (United States)

    Medina, Miguel Ángel

    2013-03-01

    Modern systems biology is already contributing to a radical transformation of molecular life sciences and biomedicine, and it is expected to have a real impact in the clinical setting in the next years. In this review, the emergence of systems biology is contextualized with a historic overview, and its present state is depicted. The present and expected future contribution of systems biology to the development of molecular medicine is underscored. Concerning the present situation, this review includes a reflection on the "inflation" of biological data and the urgent need for tools and procedures to make hidden information emerge. Descriptions of the impact of networks and models and the available resources and tools for applying them in systems biology approaches to molecular medicine are provided as well. The actual current impact of systems biology in molecular medicine is illustrated, reviewing two cases, namely, those of systems pharmacology and cancer systems biology. Finally, some of the expected contributions of systems biology to the immediate future of molecular medicine are commented.

  14. Integrated Design of Antibodies for Systems Biology Using Ab Designer

    OpenAIRE

    Pisitkun, Trairak; Dummer, Patrick; Somparn, Poorichaya; Hirankarn, Nattiya; Kopp, Jeffrey B.; Knepper, Mark A.

    2014-01-01

    In the current era of large-scale biology, systems biology has evolved as a powerful approach to identify complex interactions within biological systems. In addition to high throughput identification and quantification techniques, methods based on high-quality mono-specific antibodies remain an essential element of the approach. To assist the large-scale design and production of peptide-directed antibodies for systems biology studies, we developed a fully integrated online application, AbDesi...

  15. Computational Modeling of Biological Systems From Molecules to Pathways

    CERN Document Server

    2012-01-01

    Computational modeling is emerging as a powerful new approach for studying and manipulating biological systems. Many diverse methods have been developed to model, visualize, and rationally alter these systems at various length scales, from atomic resolution to the level of cellular pathways. Processes taking place at larger time and length scales, such as molecular evolution, have also greatly benefited from new breeds of computational approaches. Computational Modeling of Biological Systems: From Molecules to Pathways provides an overview of established computational methods for the modeling of biologically and medically relevant systems. It is suitable for researchers and professionals working in the fields of biophysics, computational biology, systems biology, and molecular medicine.

  16. Quantum integrable systems. Quantitative methods in biology

    CERN Document Server

    Feverati, Giovanni

    2011-01-01

    Quantum integrable systems have very strong mathematical properties that allow an exact description of their energetic spectrum. From the Bethe equations, I formulate the Baxter "T-Q" relation, that is the starting point of two complementary approaches based on nonlinear integral equations. The first one is known as thermodynamic Bethe ansatz, the second one as Kl\\"umper-Batchelor-Pearce-Destri- de Vega. I show the steps toward the derivation of the equations for some of the models concerned. I study the infrared and ultraviolet limits and discuss the numerical approach. Higher rank integrals of motion can be obtained, so gaining some control on the eigenvectors. After, I discuss the Hubbard model in relation to the N = 4 supersymmetric gauge theory. The Hubbard model describes hopping electrons on a lattice. In the second part, I present an evolutionary model based on Turing machines. The goal is to describe aspects of the real biological evolution, or Darwinism, by letting evolve populations of algorithms. ...

  17. The start of systems biology in Ukraine

    Directory of Open Access Journals (Sweden)

    Obolenskaya M. Yu.

    2014-01-01

    Full Text Available The first laboratory of Systems Biology in Ukraine (IMBIG NASU represents a track record of its scientific results. They include the pioneered development of a web-based tool for genome-wide surveys of eukaryotic promoters for the presence of transcription factors binding sites (COTRASIF; the deciphered mechanisms of the fine-tuned and balanced response of primary hepatocytes to interferon alpha levels recorded after partial hepatectomy; the elaboration of a novel method of gene regulatory network inference compatible with GRID environment and the development of a stoichiometric model of folate-related one carbon unit metabolism in human placenta and its application for the characteristics of the system’s behavior as a whole at different human pathologies.

  18. Integrative Systems Biology Applied to Toxicology

    DEFF Research Database (Denmark)

    Kongsbak, Kristine Grønning

    associated with combined exposure to multiple chemicals. Testing all possible combinations of the tens of thousands environmental chemicals is impractical. This PhD project was launched to apply existing computational systems biology methods to toxicological research. In this thesis, I present in three...... that were in concordance with their effects in experimental animals. In project II, I profiled the effects on rat liver gene expression levels following exposure to a 14-chemical mixture ± the presence of an endocrine disrupting chemical. This project helped us shed light on the mechanism of action...... of the 14-chemical mixture and the endocrine disrupting chemical. In project III, I modeled a predictive signature for an in vivo endpoint that is sensitive to endocrine disruption. I used publicly available data generated for the purpose of modeling predictive signatures for various in vivo endpoints. From...

  19. Nutritional Systems Biology: Definitions and Approaches

    DEFF Research Database (Denmark)

    Panagiotou, Gianni; Nielsen, Jens

    2009-01-01

    Nutrigenetics and nutrigenomics are nascent areas that are evolving quickly and riding on the wave of “personalized medicine” that is providing opportunities in the discovery and development of nutraceutical compounds. The human genome sequence and sequences of model organisms provide...... will benefit most from, or be placed at risk by, intervention strategies. More accurate assessment of the inputs to human health and the consequences of those inputs measured as accurate transcriptomic, proteomic, and metabolomic analyses would bring personalized health/diet to practice far faster than would...... waiting for a predictive knowledge of genetic variation. It is widely recognized that systems and network biology has the potential to increase our understanding of how nutrition influences metabolic pathways and homeostasis, how this regulation is disturbed in a diet-related disease, and to what extent...

  20. TissueCypher™: A systems biology approach to anatomic pathology

    Directory of Open Access Journals (Sweden)

    Jeffrey W Prichard

    2015-01-01

    Full Text Available Background: Current histologic methods for diagnosis are limited by intra- and inter-observer variability. Immunohistochemistry (IHC methods are frequently used to assess biomarkers to aid diagnoses, however, IHC staining is variable and nonlinear and the manual interpretation is subjective. Furthermore, the biomarkers assessed clinically are typically biomarkers of epithelial cell processes. Tumors and premalignant tissues are not composed only of epithelial cells but are interacting systems of multiple cell types, including various stromal cell types that are involved in cancer development. The complex network of the tissue system highlights the need for a systems biology approach to anatomic pathology, in which quantification of system processes is combined with informatics tools to produce actionable scores to aid clinical decision-making. Aims: Here, we describe a quantitative, multiplexed biomarker imaging approach termed TissueCypher™ that applies systems biology to anatomic pathology. Applications of TissueCypher™ in understanding the tissue system of Barrett's esophagus (BE and the potential use as an adjunctive tool in the diagnosis of BE are described. Patients and Methods: The TissueCypher™ Image Analysis Platform was used to assess 14 epithelial and stromal biomarkers with known diagnostic significance in BE in a set of BE biopsies with nondysplastic BE with reactive atypia (RA, n = 22 and Barrett's with high-grade dysplasia (HGD, n = 17. Biomarker and morphology features were extracted and evaluated in the confirmed BE HGD cases versus the nondysplastic BE cases with RA. Results: Multiple image analysis features derived from epithelial and stromal biomarkers, including immune biomarkers and morphology, showed significant differences between HGD and RA. Conclusions: The assessment of epithelial cell abnormalities combined with an assessment of cellular changes in the lamina propria may serve as an adjunct to conventional

  1. Microbial systems biology: New frontiers open to predictive microbiology

    NARCIS (Netherlands)

    S. Brul; F.I.C. Mensonides; K.J. Hellingwerf; M.J. Teixeira De Mattos

    2008-01-01

    The field of Systems Biology is a rapidly evolving area of research. It follows on from the previous experimental and theoretical ‘omics’ revolution in biology. Now that we have through the use of these tools many ‘indices’ of biological systems available the next step is to actually start composing

  2. Cancer-drug associations: a complex system.

    Directory of Open Access Journals (Sweden)

    Ertugrul Dalkic

    Full Text Available BACKGROUND: Network analysis has been performed on large-scale medical data, capturing the global topology of drugs, targets, and disease relationships. A smaller-scale network is amenable to a more detailed and focused analysis of the individual members and their interactions in a network, which can complement the global topological descriptions of a network system. Analysis of these smaller networks can help address questions, i.e., what governs the pairing of the different cancers and drugs, is it driven by molecular findings or other factors, such as death statistics. METHODOLOGY/PRINCIPAL FINDINGS: We defined global and local lethality values representing death rates relative to other cancers vs. within a cancer. We generated two cancer networks, one of cancer types that share Food and Drug Administration (FDA approved drugs (FDA cancer network, and another of cancer types that share clinical trials of FDA approved drugs (clinical trial cancer network. Breast cancer is the only cancer type with significant weighted degree values in both cancer networks. Lung cancer is significantly connected in the FDA cancer network, whereas ovarian cancer and lymphoma are significantly connected in the clinical trial cancer network. Correlation and linear regression analyses showed that global lethality impacts the drug approval and trial numbers, whereas, local lethality impacts the amount of drug sharing in trials and approvals. However, this effect does not apply to pancreatic, liver, and esophagus cancers as the sharing of drugs for these cancers is very low. We also collected mutation target information to generate cancer type associations which were compared with the cancer type associations derived from the drug target information. The analysis showed a weak overlap between the mutation and drug target based networks. CONCLUSIONS/SIGNIFICANCE: The clinical and FDA cancer networks are differentially connected, with only breast cancer significantly

  3. Molecular Biology of Pancreatic Cancer: How Useful Is It in Clinical Practice?

    OpenAIRE

    Sakorafas, George H; Vasileios Smyrniotis

    2012-01-01

    Context During the recent two decades dramatic advances of molecular biology allowed an in-depth understanding of pancreatic carcinogenesis. It is currently accepted that pancreatic cancer has a genetic component. The real challenge is now how these impressive advances could be used in clinical practice. Objective To critically present currently available data regarding clinical application of molecular biology in pancreatic cancer. Methods Reports about clinical implications of molecular bio...

  4. Use of colloidal gold cytochemistry in the study of the basic cell biology of cancer.

    Science.gov (United States)

    Willingham, M C

    1989-01-01

    We are currently investigating the morphologic aspects of two areas of the basic cell biology of cancer: tumor-specific surface antigens as targets for immunotoxins, and the phenomenon of multidrug resistance in chemotherapy of human tumors. Colloidal gold cytochemistry has provided a useful method for the electron-microscopic cytochemical detection of materials endocytosed by cells in culture. This technique has been used to study the internalization pathway of ligands bound to the surface of cancer cells, particularly antibodies for use as immunologic targeting reagents for the construction of immunotoxins. These colloidal gold conjugates with monoclonal antibodies have demonstrated the internalization of these immunologic reagents through coated pits and receptosomes, which is a necessary step in the delivery of immunotoxins into the cell where they can mediate their cell-killing functions. Morphologic methods have been employed for the screening and selection of monoclonal antibodies reactive with the surface of human ovarian cancer cells for use as immunotoxins and have demonstrated the in vivo activity of immunotoxins made with these antibodies and Pseudomonas exotoxin in a nude mouse model system. In other studies, we have employed such reagents for the immunocytochemical detection of the surface expression of P170, the cell-surface efflux pump protein responsible for the phenotype of multidrug resistance in tumor cells, and to investigate the distribution of this protein by using immunocytochemistry in normal human tissues. These results have suggested a role for P170 in normal cell membrane transport of metabolites in various organ systems.

  5. Personalized cancer immunotherapy using Systems Medicine approaches.

    Science.gov (United States)

    Gupta, Shailendra K; Jaitly, Tanushree; Schmitz, Ulf; Schuler, Gerold; Wolkenhauer, Olaf; Vera, Julio

    2016-05-01

    The immune system is by definition multi-scale because it involves biochemical networks that regulate cell fates across cell boundaries, but also because immune cells communicate with each other by direct contact or through the secretion of local or systemic signals. Furthermore, tumor and immune cells communicate, and this interaction is affected by the tumor microenvironment. Altogether, the tumor-immunity interaction is a complex multi-scale biological system whose analysis requires a systemic view to succeed in developing efficient immunotherapies for cancer and immune-related diseases. In this review we discuss the necessity and the structure of a systems medicine approach for the design of anticancer immunotherapies. We support the idea that the approach must be a combination of algorithms and methods from bioinformatics and patient-data-driven mathematical models conceived to investigate the role of clinical interventions in the tumor-immunity interaction. For each step of the integrative approach proposed, we review the advancement with respect to the computational tools and methods available, but also successful case studies. We particularized our idea for the case of identifying novel tumor-associated antigens and therapeutic targets by integration of patient's immune and tumor profiling in case of aggressive melanoma. PMID:26174229

  6. Personalized cancer immunotherapy using Systems Medicine approaches.

    Science.gov (United States)

    Gupta, Shailendra K; Jaitly, Tanushree; Schmitz, Ulf; Schuler, Gerold; Wolkenhauer, Olaf; Vera, Julio

    2016-05-01

    The immune system is by definition multi-scale because it involves biochemical networks that regulate cell fates across cell boundaries, but also because immune cells communicate with each other by direct contact or through the secretion of local or systemic signals. Furthermore, tumor and immune cells communicate, and this interaction is affected by the tumor microenvironment. Altogether, the tumor-immunity interaction is a complex multi-scale biological system whose analysis requires a systemic view to succeed in developing efficient immunotherapies for cancer and immune-related diseases. In this review we discuss the necessity and the structure of a systems medicine approach for the design of anticancer immunotherapies. We support the idea that the approach must be a combination of algorithms and methods from bioinformatics and patient-data-driven mathematical models conceived to investigate the role of clinical interventions in the tumor-immunity interaction. For each step of the integrative approach proposed, we review the advancement with respect to the computational tools and methods available, but also successful case studies. We particularized our idea for the case of identifying novel tumor-associated antigens and therapeutic targets by integration of patient's immune and tumor profiling in case of aggressive melanoma.

  7. Expert systems guide biological phosphorus removal

    Energy Technology Data Exchange (ETDEWEB)

    Krichten, D.J.; Wilson, K.D.; Tracy, K.D. (Air Products and Chemicals, Inc., Allentown, PA (United States))

    1991-10-01

    There is a large body of knowledge regarding optimum control strategies for new secondary wastewater treatment technology using an anaerobic selector to provide biological phosphorus removal. However, because the selector technology is new and the concepts differ somewhat from those used in conventional activated sludge wastewater treatment, a method of communicating this knowledge to plant operators is needed. Traditional methods such as classroom training and operating manuals are of limited effectiveness. The commonplace availability and low cost of the personal computer (PC) makes it practical to use a computer program to communicate the type of information required to control a wastewater treatment plant. Knowledge-based systems technology, commonly referred to as expert systems (ES) technology, is easy to use, provides useful information regarding a consistent control strategy, relieves the anxiety associated with learning a new process,' and provides instruction for inexperienced personnel. ES technology does not require special formatted input and is therefore easily accessible. All information required by the program is readily available through routine laboratory analysis, common plant instrumentation, or direct user observation. The program was designed for all levels of computer users and will run on all IBM-compatible or Apple MacIntosh systems.

  8. Biological robustness: paradigms, mechanisms, and systems principles.

    Science.gov (United States)

    Whitacre, James Michael

    2012-01-01

    Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g., mutational, environmental) are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior. PMID:22593762

  9. Biological Robustness: Paradigms, Mechanisms, and Systems Principles

    Directory of Open Access Journals (Sweden)

    James Michael Whitacre

    2012-05-01

    Full Text Available Robustness has been studied through the analysis of data sets, simulations, and a variety of experimental techniques that each have their own limitations but together confirm the ubiquity of biological robustness. Recent trends suggest that different types of perturbation (e.g. mutational, environmental are commonly stabilized by similar mechanisms, and system sensitivities often display a long-tailed distribution with relatively few perturbations representing the majority of sensitivities. Conceptual paradigms from network theory, control theory, complexity science, and natural selection have been used to understand robustness, however each paradigm has a limited scope of applicability and there has been little discussion of the conditions that determine this scope or the relationships between paradigms. Systems properties such as modularity, bow-tie architectures, degeneracy, and other topological features are often positively associated with robust traits, however common underlying mechanisms are rarely mentioned. For instance, many system properties support robustness through functional redundancy or through response diversity with responses regulated by competitive exclusion and cooperative facilitation. Moreover, few studies compare and contrast alternative strategies for achieving robustness such as homeostasis, adaptive plasticity, environment shaping, and environment tracking. These strategies share similarities in their utilization of adaptive and self-organization processes that are not well appreciated yet might be suggestive of reusable building blocks for generating robust behavior.

  10. A SYSTEMIC VISION OF BIOLOGY: OVERCOMING LINEARITY

    Directory of Open Access Journals (Sweden)

    M. Mayer

    2005-07-01

    Full Text Available Many  authors have proposed  that contextualization of reality  is necessary  to teach  Biology, empha- sizing students´ social and  economic realities.   However, contextualization means  more than  this;  it is related  to working with  different kinds of phenomena  and/or objects  which enable  the  expression of scientific concepts.  Thus,  contextualization allows the integration of different contents.  Under this perspective,  the  objectives  of this  work were to articulate different  biology concepts  in order  to de- velop a systemic vision of biology; to establish  relationships with other areas of knowledge and to make concrete the  cell molecular  structure and organization as well as their  implications  on living beings´ environment, using  contextualization.  The  methodology  adopted  in this  work  was based  on three aspects:  interdisciplinarity, contextualization and development of competences,  using energy:  its flux and transformations as a thematic axis and  an approach  which allowed the  interconnection between different situations involving  these  concepts.   The  activities developed  were:  1.   dialectic exercise, involving a movement around  micro and macroscopic aspects,  by using questions  and activities,  sup- ported  by the use of alternative material  (as springs, candles on the energy, its forms, transformations and  implications  in the  biological way (microscopic  concepts;  2, Construction of molecular  models, approaching the concepts of atom,  chemical bonds and bond energy in molecules; 3. Observations de- veloped in Manguezal¨(mangrove swamp  ecosystem (Itapissuma, PE  were used to work macroscopic concepts  (as  diversity  and  classification  of plants  and  animals,  concerning  to  energy  flow through food chains and webs. A photograph register of all activities  along the course plus texts

  11. Systems biology applied to vaccine and immunotherapy development

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2011-09-01

    Full Text Available Abstract Immunotherapies, including vaccines, represent a potent tool to prevent or contain disease with high morbidity or mortality such as infections and cancer. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the induction of protective immune responses. Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules; among those is a growing appreciation for the role the innate immunity (i.e. pathogen recognition receptors - PRRs plays in determining the nature and duration (immune memory of adaptive T and B cell immunity. The complex network of interactions between immune manipulation of the host (immunotherapy on one side and innate and adaptive responses on the other might be fully understood only employing the global level of investigation provided by systems biology. In this framework, the advancement of high-throughput technologies, together with the extensive identification of new genes, proteins and other biomolecules in the "omics" era, facilitate large-scale biological measurements. Moreover, recent development of new computational tools enables the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time. Here, we review recent progress in using systems biology to study and evaluate immunotherapy and vaccine strategies for infectious and neoplastic diseases. Multi-parametric data provide novel and often unsuspected mechanistic insights while enabling the identification of common immune signatures relevant to human investigation such as the prediction of immune responsiveness that could lead to the improvement of the design of future immunotherapy trials. Thus, the paradigm switch from "empirical" to "knowledge-based" conduct of medicine and immunotherapy in particular, leading to patient-tailored treatment.

  12. Complexity, Analysis and Control of Singular Biological Systems

    CERN Document Server

    Zhang, Qingling; Zhang, Xue

    2012-01-01

    Complexity, Analysis and Control of Singular Biological Systems follows the control of real-world biological systems at both ecological and phyisological levels concentrating on the application of now-extensively-investigated singular system theory. Much effort has recently been dedicated to the modelling and analysis of developing bioeconomic systems and the text establishes singular examples of these, showing how proper control can help to maintain sustainable economic development of biological resources. The book begins from the essentials of singular systems theory and bifurcations before tackling  the use of various forms of control in singular biological systems using examples including predator-prey relationships and viral vaccination and quarantine control. Researchers and graduate students studying the control of complex biological systems are shown how a variety of methods can be brought to bear and practitioners working with the economics of biological systems and their control will also find the ...

  13. The genetics and biology of KRAS in lung cancer

    Institute of Scientific and Technical Information of China (English)

    Peter M.K.Westcott; Minh D.To

    2013-01-01

    Mutational activation of KRAS is a common oncogenic event in lung cancer and other epithelial cancer types.Efforts to develop therapies that counteract the oncogenic effects of mutant KRAS have been largely unsuccessful,and cancers driven by mutant KRAS remain among the most refractory to available treatments.Studies undertaken over the past decades have produced a wealth of information regarding the clinical relevance of KRAS mutations in lung cancer.Mutant Kras-driven mouse models of cancer,together with cellular and molecular studies,have provided a deeper appreciation for the complex functions of KRAS in tumorigenesis.However,a much more thorough understanding of these complexities is needed before clinically effective therapies targeting mutant KRAS-driven cancers can be achieved.

  14. Molecular biology and riddle of cancer: the ‘Tom & Jerry’ show

    Directory of Open Access Journals (Sweden)

    Md. Al Mamun

    2011-11-01

    Full Text Available From the conventional Bird’s eye, cancer initiation and metastasis are generally intended to be understood beneath the light of classical clonal genetic, epigenetic and cancer stem cell model. But inspite decades of investigation, molecular biology has shown hard success to give Eagle’s eye in unraveling the riddle of cancer. And it seems, tiring Tom runs in vague behind naughty Jerry.

  15. Establishment and Its Biological Characteristics of Patient-derived Lung Cancer Xenograft Modelse

    OpenAIRE

    Zhuo, Ying; Yilong WU; Guo, Ailin; Chen, Siyuan; Su, Jian

    2010-01-01

    Background and objective With the ongoing need to improve therapy for lung cancer, there has been an increasing interest in the development of reliable preclinical models to test novel therapeutics. The aim of this study is to establish a patient-derived lung cancer xenograft model in mice and to observe the biological characteristics of xenografts. Methods Surgically resectected tumor specimens from patients with lung cancer were implanted in the subcutaneous layer of the NOD/SCID mice. Canc...

  16. Stochastic Effects in Computational Biology of Space Radiation Cancer Risk

    Science.gov (United States)

    Cucinotta, Francis A.; Pluth, Janis; Harper, Jane; O'Neill, Peter

    2007-01-01

    Estimating risk from space radiation poses important questions on the radiobiology of protons and heavy ions. We are considering systems biology models to study radiation induced repair foci (RIRF) at low doses, in which less than one-track on average transverses the cell, and the subsequent DNA damage processing and signal transduction events. Computational approaches for describing protein regulatory networks coupled to DNA and oxidative damage sites include systems of differential equations, stochastic equations, and Monte-Carlo simulations. We review recent developments in the mathematical description of protein regulatory networks and possible approaches to radiation effects simulation. These include robustness, which states that regulatory networks maintain their functions against external and internal perturbations due to compensating properties of redundancy and molecular feedback controls, and modularity, which leads to general theorems for considering molecules that interact through a regulatory mechanism without exchange of matter leading to a block diagonal reduction of the connecting pathways. Identifying rate-limiting steps, robustness, and modularity in pathways perturbed by radiation damage are shown to be valid techniques for reducing large molecular systems to realistic computer simulations. Other techniques studied are the use of steady-state analysis, and the introduction of composite molecules or rate-constants to represent small collections of reactants. Applications of these techniques to describe spatial and temporal distributions of RIRF and cell populations following low dose irradiation are described.

  17. Systems Biology in Aging: Linking the Old and the Young

    OpenAIRE

    HOU, LEI; Huang, Jialiang; Green, Christopher D.; Boyd-Kirkup, Jerome; Zhang, Wei; Yu, Xiaoming; Gong, Wenxuan; Zhou, Bing; Jing-Dong J Han

    2012-01-01

    Aging can be defined as a process of progressive decline in the physiological capacity of an organism, manifested by accumulated alteration and destabilization at the whole system level. Systems biology approaches offer a promising new perspective to examine the old problem of aging. We begin this review by introducing the concepts of systems biology, and then illustrate the application of systems biology approaches to aging research, from gene expression profiling to network analysis. We the...

  18. The New Lung Cancer Staging System

    Institute of Scientific and Technical Information of China (English)

    Frank C. Detterbeck,MD, FCCP; Daniel J. Boffa, MD; Lynn T, Tanoue, MD, FCCP

    2009-01-01

    The International Association for the Study of Lung Cancer (IASLC) has conducted an extensive initiative to inform the revision of the lung cancer staging system. This involved development of an international database along with extensive analysis of a large population of patients and their prognoses. This article reviews the recommendations of the IASLC International Staging Committee for the definitions for the TNM descriptors and the stage grouping in the new non-small cell lung cancer staging system.

  19. Biological modelling of the radiation dose escalation effect of regional hyperthermia in cervical cancer

    International Nuclear Information System (INIS)

    Locoregional hyperthermia combined with radiotherapy significantly improves locoregional control and overall survival for cervical tumors compared to radiotherapy alone. In this study biological modelling is applied to quantify the effect of radiosensitization for three cervical cancer patients to evaluate the improvement in equivalent dose for the combination treatment with radiotherapy and hyperthermia. The Linear-Quadratic (LQ) model extended with temperature-dependent LQ-parameters α and β was used to model radiosensitization by hyperthermia and to calculate the conventional radiation dose that is equivalent in biological effect to the combined radiotherapy and hyperthermia treatment. External beam radiotherapy planning was performed based on a prescription dose of 46Gy in 23 fractions of 2Gy. Hyperthermia treatment using the AMC-4 system was simulated based on the actual optimized system settings used during treatment. The simulated hyperthermia treatments for the 3 patients yielded a T50 of 40.1 °C, 40.5 °C, 41.1 °C and a T90 of 39.2 °C, 39.7 °C, 40.4 °C, respectively. The combined radiotherapy and hyperthermia treatment resulted in a D95 of 52.5Gy, 55.5Gy, 56.9Gy in the GTV, a dose escalation of 7.3–11.9Gy compared to radiotherapy alone (D95 = 45.0–45.5Gy). This study applied biological modelling to evaluate radiosensitization by hyperthermia as a radiation-dose escalation for cervical cancer patients. This model is very useful to compare the effectiveness of different treatment schedules for combined radiotherapy and hyperthermia treatments and to guide the design of clinical studies on dose escalation using hyperthermia in a multi-modality setting

  20. Correlative Study on MRI Morphologic Features,Pathology, and Molecular Biology of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Rong Chen; Shuigen Gong; Weiguo Zhang; Jinhua Chen; Shuangwu He; Baohua Liu; Zengpeng Li

    2005-01-01

    OBJECTIVE To investigate the correlation among MRI morphologic features,pathology, and molecular biology of breast cancer.METHORDS MRI was used to analyze the morphologic features of breast cancers of 78 patients before operation. The mastectomy specimens of the breast neoplasms were immunohistochemically stained, and the expression of the estrogen (ER), progesterone receptor (PR), C-erbB-2, P53, and the distribution of microvessel density (MVD) measured. The pathologic results were compared with the MRI features.RESULTS Among the 80 breast cancers, ER positive expression was positively correlated with the spicular contour of breast cancers (P<0.01),while showing a significant inverse correlation with the T-stage (P<0.05). CerbB-2 and P53 positive expression were positively correlated with the necrotic center of the cancers (P<0.05). The expression of PR was not significantly correlated with the spicular contour, obscure margin, necrotic center, and T-stage of these cancers (P>0.05). Among 41 breast cancers examined with dynamic contrast enhanced MR, there was a positive correlation between the spatial distribution of the contrast agent and MVD(P<0.01).CONCLUSION To a certain extent there is some correlation among the MRI morphologic features, pathology, and molecular biological factors in breast cancer. The biological behavior and prognosis of breast cancer can be assessed based on MRI features.

  1. Apparatus and Methods for Manipulation and Optimization of Biological Systems

    Science.gov (United States)

    Ho, Chih-Ming (Inventor); Wong, Pak Kin (Inventor); Sun, Ren (Inventor); Yu, Fuqu (Inventor)

    2014-01-01

    The invention provides systems and methods for manipulating biological systems, for example to elicit a more desired biological response from a biological sample, such as a tissue, organ, and/or a cell. In one aspect, the invention operates by efficiently searching through a large parametric space of stimuli and system parameters to manipulate, control, and optimize the response of biological samples sustained in the system. In one aspect, the systems and methods of the invention use at least one optimization algorithm to modify the actuator's control inputs for stimulation, responsive to the sensor's output of response signals. The invention can be used, e.g., to optimize any biological system, e.g., bioreactors for proteins, and the like, small molecules, polysaccharides, lipids, and the like. Another use of the apparatus and methods includes is for the discovery of key parameters in complex biological systems.

  2. Systems biology of microbial exopolysaccharides production

    Directory of Open Access Journals (Sweden)

    Ozlem eAtes

    2015-12-01

    Full Text Available Exopolysaccharides (EPS produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture and medicine. EPSs are mainly associated with high-value applications and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore a systems-based approach constitutes an important step towards understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan and dextran.

  3. Modeling and Simulation Tools: From Systems Biology to Systems Medicine.

    Science.gov (United States)

    Olivier, Brett G; Swat, Maciej J; Moné, Martijn J

    2016-01-01

    Modeling is an integral component of modern biology. In this chapter we look into the role of the model, as it pertains to Systems Medicine, and the software that is required to instantiate and run it. We do this by comparing the development, implementation, and characteristics of tools that have been developed to work with two divergent methodologies: Systems Biology and Pharmacometrics. From the Systems Biology perspective we consider the concept of "Software as a Medical Device" and what this may imply for the migration of research-oriented, simulation software into the domain of human health.In our second perspective, we see how in practice hundreds of computational tools already accompany drug discovery and development at every stage of the process. Standardized exchange formats are required to streamline the model exchange between tools, which would minimize translation errors and reduce the required time. With the emergence, almost 15 years ago, of the SBML standard, a large part of the domain of interest is already covered and models can be shared and passed from software to software without recoding them. Until recently the last stage of the process, the pharmacometric analysis used in clinical studies carried out on subject populations, lacked such an exchange medium. We describe a new emerging exchange format in Pharmacometrics which covers the non-linear mixed effects models, the standard statistical model type used in this area. By interfacing these two formats the entire domain can be covered by complementary standards and subsequently the according tools.

  4. From Biology to Targeted Cancer Treatment and Prevention

    Institute of Scientific and Technical Information of China (English)

    Li MAO

    2009-01-01

    @@ Cancer is a complex disease involving accumulation of multiple molecular abnormalities during a long period of time. Because the differences in tim-ing and types of abnormalities, together with differences in inherited genetic background of individuals, patients with even same type cancer may experi- ence dramatically different clinical presentations and outcomes.

  5. Human breast cancer: its genetics, biology and prognosis

    NARCIS (Netherlands)

    M. Riaz (Muhammad)

    2013-01-01

    textabstractCancer is a major public health problem, being the second leading cause of death, after cardiovascular diseases1. Among women, breast cancer is the first neoplasm for incidence and the second for mortality all over the world. World-wide, an incidence of 1.4 million new cases and a mortal

  6. Targeting cancer epigenetics: Linking basic biology to clinical medicine.

    Science.gov (United States)

    Shinjo, Keiko; Kondo, Yutaka

    2015-12-01

    Recent studies provide compelling evidence that epigenetic dysregulation is involved in almost every step of tumor development and progression. Differences in tumor behavior, which ultimately reflects clinical outcome, can be explained by variations in gene expression patterns generated by epigenetic mechanisms, such as DNA methylation. Therefore, epigenetic abnormalities are considered potential biomarkers and therapeutic targets. DNA methylation is stable at certain specific loci in cancer cells and predominantly reflects the characteristic clinicopathological features. Thus, it is an ideal biomarker for cancer screening, classification and prognostic purposes. Epigenetic treatment for cancers is based on the pharmacologic targeting of various core transcriptional programs that sustains cancer cell identity. Therefore, targeting aberrant epigenetic modifiers may be effective for multiple processes compared with using a selective inhibitor of aberrant single signaling pathway. This review provides an overview of the epigenetic alterations in human cancers and discusses about novel therapeutic strategies targeting epigenetic alterations.

  7. Cancer Stem Cells: Biological Functions and Therapeutically Targeting

    Directory of Open Access Journals (Sweden)

    Marius Eugen Ciurea

    2014-05-01

    Full Text Available Almost all tumors are composed of a heterogeneous cell population, making them difficult to treat. A small cancer stem cell population with a low proliferation rate and a high tumorigenic potential is thought to be responsible for cancer development, metastasis and resistance to therapy. Stem cells were reported to be involved in both normal development and carcinogenesis, some molecular mechanisms being common in both processes. No less controversial, stem cells are considered to be important in treatment of malignant diseases both as targets and drug carriers. The efforts to understand the role of different signalling in cancer stem cells requires in depth knowledge about the mechanisms that control their self-renewal, differentiation and malignant potential. The aim of this paper is to discuss insights into cancer stem cells historical background and to provide a brief review of the new therapeutic strategies for targeting cancer stem cells.

  8. Exploring Synthetic and Systems Biology at the University of Edinburgh.

    Science.gov (United States)

    Fletcher, Liz; Rosser, Susan; Elfick, Alistair

    2016-06-15

    The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme.

  9. Quantifying electron transfer reactions in biological systems

    DEFF Research Database (Denmark)

    Sjulstok, Emil Sjulstok; Olsen, Jógvan Magnus Haugaard; Solov'yov, Ilia A

    2015-01-01

    which for example occur in photosynthesis, cellular respiration, DNA repair, and possibly magnetic field sensing. Quantum biology uses computation to model biological interactions in light of quantum mechanical effects and has primarily developed over the past decade as a result of convergence between...

  10. Study on biological characters of SGC7901 gastric cancer cell-dendritic cell fusion vaccines

    Institute of Scientific and Technical Information of China (English)

    Kun Zhang; Peng-Fen Gao; Pei-Wu Yu; Yun Rao; Li-Xin Zhou

    2006-01-01

    AIM: To detect the biological characters of the SGC7901 gastric cancer cell-dendritic cell fusion vaccines.METHODS: The suspending living SGC7901 gastric cancer cells and dendritic cells were induced to be fusioned by polyethylene glycol. Pure fusion cells were obtained by selective culture with the HAT/HT culture systems.The fusion cells were counted at different time points of culture and their growth curves were drawn to reflect their proliferative activities. The fusion cells were also cultured in culture medium to investigate whether they could grow into cell clones. MTT method was used to test the stimulating abilities of the fusion cells on T lymphocytes' proliferations. Moreover, the fusion cells were planted into nude mice to observe whether they could grow into new planted tumors in this kind of immunodeficiency animals.RESULTS: The fusion cells had weaker proliferative activity and clone abilities than their parental cells. When they were cultured, the counts of cells did not increase remarkably, nor could they grow into cell clones in culture medium. The fusion cells could not grow into new planted tumors after planted into nude mice. The stimulating abilities of the fusion cells on T lymphocytes' proliferations were remarkably increased than their parental dendritic cells.CONCLUSION: The SGC7901 gastric cancer cell-dendritic cell fusion vaccines have much weaker proliferative abilities than their parental cells, but they keep strong abilities to irritate the T lymphocytes and have no abilities to grow into new planted tumors in immunodeficiency animals. These are the biological basis for their antitumor biotherapies.

  11. Developing integrated TOF-SIMS/MALDI IMS system in studying biological systems

    Science.gov (United States)

    Wu, Ligang

    Using imaging mass spectrometry (IMS) techniques (including TOF-SIMS and MALDI IMS) to study biological systems is a relatively new concept and quickly gained popularity in recent years. Imaging mass spectrometry is a discovery technology that utilizes a focused ion beam or laser beam to desorb ions from sample surface. By detecting the desorbed ions, the chemical distributions and biological changes of a sample surface can be analyzed. These techniques offer a new analytical imaging approach to investigate biological processes at the cellular and tissue level. In this research, a novel integrated TOF-SIMS/MALDI IMS system as well as IMS based biological-sample-preparation techniques and data-reduction methods are developed. We then demonstrate the power of these techniques in studying different biological systems, including monosaccharides isomers, human breast cancer cell lines, mouse embryo tissues and mouse kidney sections. Using TOF-SIMS and statistical analysis methods, seven monosaccharide isomers are fully differentiated by analyzing their characteristic spectral pattern. In addition, a deep understanding of the fragmentation pathway of these isomers under ion bombardment is gained. In an application of TOF-SIMS to the differentiation of three human breast cancer cell lines, MCF-7, T47D, and MDA-MB-231, we show that principal component analysis (PCA) data reduction of TOF-SIMS spectra can differentiate cellular compartments (cytosol, nuclear and particulate) within the cell types, as well as homogenates from among the three cell lines. In a tissue-specific application, we extend the analytical capabilities of TOF-SIMS and PCA by imaging and differentiating Formalin-fixed paraffin-embedded (FFPE) mouse embryo tissues. We demonstrate reproducible differentiation of six tissue types based on the remaining small molecules after paraffin-embedding and the fragments of the cellular proteins. In a unique study of fresh frozen mouse kidney tissues, both TOF

  12. Commentary: Systems Biology and Its Relevance to Alcohol Research

    OpenAIRE

    Guo, Q. Max; Zakhari, Sam

    2008-01-01

    Systems biology, a new scientific discipline, aims to study the behavior of a biological organization or process in order to understand the function of a dynamic system. This commentary will put into perspective topics discussed in this issue of Alcohol Research & Health, provide insight into why alcohol-induced disorders exemplify the kinds of conditions for which a systems biological approach would be fruitful, and discuss the opportunities and challenges facing alcohol researchers.

  13. Interactive analysis of systems biology molecular expression data

    OpenAIRE

    Prabhakar Sunil; Salt David E; Kane Michael D; Stephenson Alan; Ouyang Qi; Zhang Mingwu; Burgner John; Buck Charles; Zhang Xiang

    2008-01-01

    Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferr...

  14. Influence of low intensity laser radiation on different biological systems

    OpenAIRE

    Tsivunchyk, Olga S.

    2004-01-01

    Abstract There are a lot of examples and contradictory results concerning influence of low intensity laser irradiation (LILI) on biological objects. In this work with a number of experiments the influence of LILI on different biological systems was investigated. For the carried out experiments the following biological objects and systems were used: * different enzymes of anti-oxidant system of animals (i.e. catalase, superoxide-di...

  15. Advanced Systems Biology Methods in Drug Discovery and Translational Biomedicine

    OpenAIRE

    Jun Zou; Ming-Wu Zheng; Gen Li; Zhi-Guang Su

    2013-01-01

    Systems biology is in an exponential development stage in recent years and has been widely utilized in biomedicine to better understand the molecular basis of human disease and the mechanism of drug action. Here, we discuss the fundamental concept of systems biology and its two computational methods that have been commonly used, that is, network analysis and dynamical modeling. The applications of systems biology in elucidating human disease are highlighted, consisting of human disease networ...

  16. The prognostic significance of apoptosis-related biological markers in Chinese gastric cancer patients.

    Directory of Open Access Journals (Sweden)

    Xiaowen Liu

    Full Text Available BACKGROUND AND OBJECTIVE: The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as p53, bcl-2, bax, and c-myc, and clinicopathological features and their prognostic value. METHODS: From 1996 to 2007, 4426 patients had undergone curative D2 gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 501 patients, the expression levels of p53, bcl-2, bax, and c-myc were examined by immunohistochemistry. The prognostic value of biological markers and the correlation between biological markers and other clinicopathological factors were investigated. RESULTS: There were 339 males and 162 females with a mean age of 57. The percentages of positive expression of p53, bcl-2, bax, and c-myc were 65%, 22%, 43%, and 58%, respectively. There was a strong correlation between p53, bax, and c-myc expression (P=0.00. There was significant association between bcl-2, and bax expression (P<0.05. p53 expression correlated with histological grade (P=0.01; bcl-2 expression with pathological stage (P=0.00; bax expression with male (P=0.02, histological grade (P=0.01, Borrmann type (P=0.01, tumor location (P=0.00, lymph node metastasis (P=0.03, and pathological stage (P=0.03; c-myc expression with Borrmann type (P=0.00. bcl-2 expression was related with good survival in univariate analysis (P=0.01. Multivariate analysis showed that bcl-2 expression and pathological stage were defined as independent prognostic factors. There were significant differences of overall 5-year survival rates according to bcl-2 expression or not in stage IIB (P=0.03. CONCLUSION: The expression of bcl-2 was an independent prognostic factor for patients with gastric cancer; it might be a candidate for the gastric cancer staging system.

  17. Stem cell biology in thyroid cancer: Insights for novel therapies

    Institute of Scientific and Technical Information of China (English)

    Parisha; Bhatia; Koji; Tsumagari; Zakaria; Y; Abd; Elmageed; Paul; Friedlander; Joseph; F; Buell; Emad; Kandil

    2014-01-01

    Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.

  18. Stem cell biology in thyroid cancer: Insights for novel therapies

    Science.gov (United States)

    Bhatia, Parisha; Tsumagari, Koji; Abd Elmageed, Zakaria Y; Friedlander, Paul; Buell, Joseph F; Kandil, Emad

    2014-01-01

    Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review. PMID:25426258

  19. Machine learning methods in the computational biology of cancer.

    Science.gov (United States)

    Vidyasagar, M

    2014-07-01

    The objectives of this Perspective paper are to review some recent advances in sparse feature selection for regression and classification, as well as compressed sensing, and to discuss how these might be used to develop tools to advance personalized cancer therapy. As an illustration of the possibilities, a new algorithm for sparse regression is presented and is applied to predict the time to tumour recurrence in ovarian cancer. A new algorithm for sparse feature selection in classification problems is presented, and its validation in endometrial cancer is briefly discussed. Some open problems are also presented.

  20. Cancer cells: novel expression systems in pharmaceutical biotechnology

    Directory of Open Access Journals (Sweden)

    Sayed Shahabuddin Hoseini

    2010-10-01

    Full Text Available "nEvery day, numerous medications are used worldwide to treat different kinds of diseases. A huge part of drug manufacturing - is done in pharmaceutical biotechnology companies. Scientists have developed a variety of methods to synthesize these substances. They can insert the gene or the cDNA of a desired protein into special expression systems and extract the resulted products using different methods. The paraneoplastic syndromes are signs and symptoms originated from cancer cell derived products and not because of direct invasion of tumor cells or metastasis. Cancer cells can secret a wide variety of products such as growth hormones, antibodies and so on. In an innovative route, these products may be processed further and eventually be used as useful biologic substances. In this manuscript, we described a process by which scientists can use cancer cells in order to produce various types of biological substances which can be used as medications, diagnostic substances and research materials. Our hypothesis has been inspired from autonomous production of biologic substances from those cancer cells that are responsible for manifestations of paraneoplastic syndromes.

  1. MEMBRANE COMPUTING AS THE PARADIGM FOR MODELING SYSTEMS BIOLOGY

    Directory of Open Access Journals (Sweden)

    Ravie Chandren Muniyandi

    2013-01-01

    Full Text Available Membrane computing is a field in computer science that is inspired from the structure and the processes of living cells and is being considered as an alternative in solving the limitations in conventional mathematical approaches by taking into consideration its essential features that are of interest for research in systems biology. Advancements in computability make it feasible to handle huge volumes of data in biology and propose a new and better approach using a discreet computer science model, such as membrane computing. In this respect, membrane-computing abilities, to enhance the understanding of the system level of biological systems, have been explored. This study discusses experiences in applying membrane computing in modeling biological systems as well as possibilities of incorporating membrane computing into other computer science paradigms to enhance the use of membrane computing in systems biology. Experiences in modeling aspects of systems biology with membrane computing demonstrate additional advantages and possibilities compared with conventional methods. However, they are not yet used widely to model or simulate biological processes or systems. A general framework of modeling and verifying biological systems using membrane computing is essential as a guideline for biologists in their research in systems biology.

  2. Peroxisystem: harnessing systems cell biology to study peroxisomes.

    Science.gov (United States)

    Schuldiner, Maya; Zalckvar, Einat

    2015-04-01

    In recent years, high-throughput experimentation with quantitative analysis and modelling of cells, recently dubbed systems cell biology, has been harnessed to study the organisation and dynamics of simple biological systems. Here, we suggest that the peroxisome, a fascinating dynamic organelle, can be used as a good candidate for studying a complete biological system. We discuss several aspects of peroxisomes that can be studied using high-throughput systematic approaches and be integrated into a predictive model. Such approaches can be used in the future to study and understand how a more complex biological system, like a cell and maybe even ultimately a whole organism, works.

  3. A guide to numerical modelling in systems biology

    CERN Document Server

    Deuflhard, Peter

    2015-01-01

    This book is intended for students of computational systems biology with only a limited background in mathematics. Typical books on systems biology merely mention algorithmic approaches, but without offering a deeper understanding. On the other hand, mathematical books are typically unreadable for computational biologists. The authors of the present book have worked hard to fill this gap. The result is not a book on systems biology, but on computational methods in systems biology. This book originated from courses taught by the authors at Freie Universität Berlin. The guiding idea of the courses was to convey those mathematical insights that are indispensable for systems biology, teaching the necessary mathematical prerequisites by means of many illustrative examples and without any theorems. The three chapters cover the mathematical modelling of biochemical and physiological processes, numerical simulation of the dynamics of biological networks, and identification of model parameters by means of comparisons...

  4. Biology of cancer: thermodynamic answers to some questions.

    Science.gov (United States)

    Klimek, R

    2001-12-01

    All the theories of carcinogenesis have properly described this event from methodologically different points of view (medical, biological, social, biochemical psychological etc.). The point is that one should understand the thermodynamical rules underlying each of these approaches. On this level of knowledge, quantum thermodynamics combines matter and energy, while technical quantization in a novel way differentiates precancerous states as the dissipathogenic ones from the neoplasms as the newly formed dissipative structures (systems). From the essential nature of the neoplasm one can derive some general rules of therapy which focus mainly on: 1 degrees prevention and therapy of the dissipathogenic states, 2 degrees strengthening of the regenerative and defensive mechanisms of the organism and, finally, 3 degrees removal of neoplastic changes as widely as necessary but also as sparingly as possible. For a long time, these rules have been observed in reverse order. That cannot improve the medical outcome, which has not changed for a few dozen years, i.e. recovery depending on the clinical level at the moment of the diagnosis.

  5. Mathematical models in cell biology and cancer chemotherapy

    CERN Document Server

    Eisen, Martin

    1979-01-01

    The purpose of this book is to show how mathematics can be applied to improve cancer chemotherapy. Unfortunately, most drugs used in treating cancer kill both normal and abnormal cells. However, more cancer cells than normal cells can be destroyed by the drug because tumor cells usually exhibit different growth kinetics than normal cells. To capitalize on this last fact, cell kinetics must be studied by formulating mathematical models of normal and abnormal cell growth. These models allow the therapeutic and harmful effects of cancer drugs to be simulated quantitatively. The combined cell and drug models can be used to study the effects of different methods of administering drugs. The least harmful method of drug administration, according to a given criterion, can be found by applying optimal control theory. The prerequisites for reading this book are an elementary knowledge of ordinary differential equations, probability, statistics, and linear algebra. In order to make this book self-contained, a chapter on...

  6. Biological Markers May Indicate Poor Breast Cancer Prognosis

    Science.gov (United States)

    A team of researchers has found an association between breast cancer survival and two proteins that, when present in the blood in high levels, are indicators of inflammation. Using data from the Health, Eating, Activity and Lifestyle (HEAL) study sponsor

  7. Procathepsin D and cancer: From molecular biology to clinical applications

    OpenAIRE

    Vetvicka, Vaclav; Vashishta, Aruna; Saraswat-Ohri, Sujata; Vetvickova, Jana

    2010-01-01

    Procathepsin D (pCD) is overexpressed and secreted by cells of various tumor types including breast and lung carcinomas. pCD affects multiple features of tumor cells including proliferation, invasion, metastases and apoptosis. Several laboratories have previously shown that the mitogenic effect of pCD on cancer cells is mediated via its propeptide part (APpCD). However, the exact mechanism of how pCD affects cancer cells has not been identified. Recent observations have also revealed the poss...

  8. Inflammatory breast cancer: unique biological and therapeutic considerations.

    Science.gov (United States)

    Woodward, Wendy A

    2015-11-01

    Through the concerted efforts of many patients, health-care providers, legislators, and other supporters, the past decade has seen the development of the first clinics dedicated to the care of patients with inflammatory breast cancer in the USA and other countries. Together with social networking, advocacy, and education, a few specialised centres have had substantial increases in patient numbers (in some cases ten times higher), which has further expanded the community of science and advocacy and increased the understanding of the disease process. Although inflammatory breast cancer is considered rare, constituting only 2-4% of breast cancer cases, poor prognosis means that patients with the disease account for roughly 10% of breast cancer mortality annually in the USA. I propose that the unique presentation of inflammatory breast cancer might require specific, identifiable changes in the breast parenchyma that occur before the tumour-initiating event. This would make the breast tissue itself a tumour-promoting medium that should be treated as a component of the pathology in multidisciplinary treatment and should be further studied for complementary targets to inhibit the pathobiology that is specific to inflammatory breast cancer. PMID:26545845

  9. Industrial systems biology and its impact on synthetic biology of yeast cell factories.

    Science.gov (United States)

    Fletcher, Eugene; Krivoruchko, Anastasia; Nielsen, Jens

    2016-06-01

    Engineering industrial cell factories to effectively yield a desired product while dealing with industrially relevant stresses is usually the most challenging step in the development of industrial production of chemicals using microbial fermentation processes. Using synthetic biology tools, microbial cell factories such as Saccharomyces cerevisiae can be engineered to express synthetic pathways for the production of fuels, biopharmaceuticals, fragrances, and food flavors. However, directing fluxes through these synthetic pathways towards the desired product can be demanding due to complex regulation or poor gene expression. Systems biology, which applies computational tools and mathematical modeling to understand complex biological networks, can be used to guide synthetic biology design. Here, we present our perspective on how systems biology can impact synthetic biology towards the goal of developing improved yeast cell factories. Biotechnol. Bioeng. 2016;113: 1164-1170. © 2015 Wiley Periodicals, Inc.

  10. A unified biological modeling and simulation system for analyzing biological reaction networks

    Science.gov (United States)

    Yu, Seok Jong; Tung, Thai Quang; Park, Junho; Lim, Jongtae; Yoo, Jaesoo

    2013-12-01

    In order to understand the biological response in a cell, a researcher has to create a biological network and design an experiment to prove it. Although biological knowledge has been accumulated, we still don't have enough biological models to explain complex biological phenomena. If a new biological network is to be created, integrated modeling software supporting various biological models is required. In this research, we design and implement a unified biological modeling and simulation system, called ezBioNet, for analyzing biological reaction networks. ezBioNet designs kinetic and Boolean network models and simulates the biological networks using a server-side simulation system with Object Oriented Parallel Accelerator Library framework. The main advantage of ezBioNet is that a user can create a biological network by using unified modeling canvas of kinetic and Boolean models and perform massive simulations, including Ordinary Differential Equation analyses, sensitivity analyses, parameter estimates and Boolean network analysis. ezBioNet integrates useful biological databases, including the BioModels database, by connecting European Bioinformatics Institute servers through Web services Application Programming Interfaces. In addition, we employ Eclipse Rich Client Platform, which is a powerful modularity framework to allow various functional expansions. ezBioNet is intended to be an easy-to-use modeling tool and a simulation system for understanding the control mechanism by monitoring the change of each component in a biological network. The simulation result can be managed and visualized on ezBioNet, which is available free of charge at http://ezbionet.sourceforge.net or http://ezbionet.cbnu.ac.kr.

  11. 3-Dimensional quantitative detection of nanoparticle content in biological tissue samples after local cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Rahn, Helene, E-mail: helene.rahn@gmail.com [Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Technische Universitaet Dresden, Dresden 01069 (Germany); Alexiou, Christoph [ENT-Department, Section for Experimental Oncology and Nanomedicine (Else Kröner-Fresenius-Stiftungsprofessur), University Hospital Erlangen, Waldstraße 1, Erlangen 91054 (Germany); Trahms, Lutz [Physikalisch-Technische Bundesanstalt, Abbestraße 2-12, Berlin 10587 (Germany); Odenbach, Stefan [Institute of Fluid Mechanics, Chair of Magnetofluiddynamics, Technische Universitaet Dresden, Dresden 01069 (Germany)

    2014-06-01

    X-ray computed tomography is nowadays used for a wide range of applications in medicine, science and technology. X-ray microcomputed tomography (XµCT) follows the same principles used for conventional medical CT scanners, but improves the spatial resolution to a few micrometers. We present an example of an application of X-ray microtomography, a study of 3-dimensional biodistribution, as along with the quantification of nanoparticle content in tumoral tissue after minimally invasive cancer therapy. One of these minimal invasive cancer treatments is magnetic drug targeting, where the magnetic nanoparticles are used as controllable drug carriers. The quantification is based on a calibration of the XµCT-equipment. The developed calibration procedure of the X-ray-µCT-equipment is based on a phantom system which allows the discrimination between the various gray values of the data set. These phantoms consist of a biological tissue substitute and magnetic nanoparticles. The phantoms have been studied with XµCT and have been examined magnetically. The obtained gray values and nanoparticle concentration lead to a calibration curve. This curve can be applied to tomographic data sets. Accordingly, this calibration enables a voxel-wise assignment of gray values in the digital tomographic data set to nanoparticle content. Thus, the calibration procedure enables a 3-dimensional study of nanoparticle distribution as well as concentration. - Highlights: • Local cancer treatments are promising in reducing negative side effects occurring during conventional chemotherapy. • The nanoparticles play an important role in delivering drugs to the designated area during local cancer treatments as magnetic drug targeting. • We study the nanoparticles distribution in tumor tissue after magnetic drug targeting with X-ray computed tomography. • We achieved a 3-dimensional quantification of the nanoparticles content in tumor tissue out of digital tomographic data.

  12. Biological basis of personalized anticoagulation in cancer: oncogene and oncomir networks as putative regulators of coagulopathy.

    Science.gov (United States)

    D'Asti, Esterina; Rak, Janusz

    2016-04-01

    Activation of stromal response pathways in cancer is increasingly viewed as both a local and systemic extension of molecular alterations driving malignant transformation. Rather than reflecting passive and unspecific responses to anatomical abnormalities, the coagulation system is a target of oncogenic deregulation, impacting the role of clotting and fibrinolytic proteins, and integrating hemostasis, inflammation, angiogenesis and cellular growth effects in cancer. These processes signify, but do not depend on, the clinically manifest coagulopathy and thrombosis. In this regard, the role of driver mutations affecting oncoprotein coding genes such as RAS, EGFR or MET and tumour suppressors (PTEN, TP53) are well described as regulators of tissue factor (TF), protease activated receptors (PAR-1/2) and ectopic coagulation factors (FVII). Indeed, in both adult and pediatric brain tumours the expression patterns of coagulation and angiogenesis regulators (coagulome and angiome, respectively) reflect the molecular subtypes of the underlying diseases (glioblastoma or medulloblastoma) as defined by their oncogenic classifiers and clinical course. This emerging understanding is still poorly established in relation to the transforming effects of non-coding genes, including those responsible for the expression of microRNA (miR). Indeed, several miRs have been recently found to regulate TF and other effectors. We recently documented that in the context of the aggressive embryonal tumour with multilayered rosettes (ETMR) the oncogenic driver miR (miR-520g) suppresses the expression of TF and correlates with hypocoagulant tumour characteristics. Unlike in adult cancers, the growth of pediatric embryonal brain tumour cells as spheres (to maintain stem cell properties) results in upregulation of miR-520g and downregulation of TF expression and activity. We postulate that oncogenic protein and miR coding genes form alternative pathways of coagulation system regulation in different

  13. A Magnetic Sensor System for Biological Detection

    KAUST Repository

    Li, Fuquan

    2015-05-01

    Magnetic biosensors detect biological targets through sensing the stray field of magnetic beads which label the targets. Commonly, magnetic biosensors employ the “sandwich” method to immobilize biological targets, i.e., the targets are sandwiched between a bio-functionalized sensor surface and bio-functionalized magnetic beads. This method has been used very successfully in different application, but its execution requires a rather elaborate procedure including several washing and incubation steps. This dissertation investigates a new magnetic biosensor concept, which enables a simple and effective detection of biological targets. The biosensor takes advantage of the size difference between bare magnetic beads and compounds of magnetic beads and biological targets. First, the detection of super-paramagnetic beads via magnetic tunnel junction (MTJ) sensors is implemented. Frequency modulation is used to enhance the signal-to-noise ratio, enabling the detection of a single magnetic bead. Second, the concept of the magnetic biosensor is investigated theoretically. The biosensor consists of an MTJ sensor, which detects the stray field of magnetic beads inside of a trap on top of the MTJ. A microwire between the trap and the MTJ is used to attract magnetic beads to the trapping well by applying a current to it. The MTJ sensor’s output depends on the number of beads inside the trap. If biological targets are in the sample solution, the beads will form bead compounds consisting of beads linked to the biological targets. Since bead compounds are larger than bare beads, the number of beads inside the trapping well will depend on the presence of biological targets. Hence, the output of the MTJ sensor will depend on the biological targets. The dependences of sensor signals on the sizes of the MTJ sensor, magnetic beads and biological targets are studied to find the optimum constellations for the detection of specific biological targets. The optimization is demonstrated

  14. Dynamics and kinetics of model biological systems

    Science.gov (United States)

    Mirigian, Stephen

    In this work we study three systems of biological interest: the translocation of a heterogeneously charged polymer through an infinitely thin pore, the wrapped of a rigid particle by a soft vesicle and the modification of the dynamical properties of a gel due to the presence of rigid inclusions. We study the kinetics of translocation for a heterogeneously charged polyelectrolyte through an infinitely narrow pore using the Fokker-Planck formalism to compute mean first passage times, the probability of successful translocation, and the mean successful translocation time for a diblock copolymer. We find, in contrast to the homopolymer result, that details of the boundary conditions lead to qualitatively different behavior. Under experimentally relevant conditions for a diblock copolymer we find that there is a threshold length of the charged block, beyond which the probability of successful translocation is independent of charge fraction. Additionally, we find that mean successful translocation time exhibits non-monotonic behavior with increasing length of the charged fraction; there is an optimum length of the charged block where the mean successful translocation time is slowest and there can be a substantial range of charge fraction where it is slower than a minimally charged chain. For a fixed total charge on the chain, we find that finer distributions of the charge along the chain leads to a significant reduction in mean translocation time compared to the diblock distribution. Endocytosis is modeled using a simple geometrical model from the literature. We map the process of wrapping a rigid spherical bead onto a one-dimensional stochastic process described by the Fokker-Planck equation to compute uptake rates as a function of membrane properties and system geometry. We find that simple geometrical considerations pick an optimal particle size for uptake and a corresponding maximal uptake rate, which can be controlled by altering the material properties of the

  15. Body fatness as a cause of cancer: epidemiologic clues to biologic mechanisms.

    Science.gov (United States)

    Byers, Tim; Sedjo, Rebecca L

    2015-06-01

    Carrying excess body fat is a leading cause of cancer. Epidemiologic evidence gives strong clues about the mechanisms that link excess adiposity to risk for several cancer sites. For postmenopausal breast cancer and endometrial cancer, the hyper-estrogenic state that is induced by excess body fatness is the likely cause. For esophageal cancer and gallbladder cancer, chronic local inflammation induced by acid reflux and gallstones is the likely cause, and for liver cancer, local inflammation induced by hepatic fatty infiltration is the likely cause. However, for several other cancers known to be associated with excess adiposity, including cancers of the colon, pancreas, ovary, kidney, and prostate, specific causes are not known. Possible candidates include elevated systemic or local tissue inflammation induced by adiposity and effects of the elevated levels of leptin, insulin, IGFs, and depressed immune function that are seen with excess adiposity. There is growing evidence that intentional weight loss not only reduces circulating levels of cancer-associated factors but that it also reduces cancer incidence and recurrence. Better research is needed to understand the mechanisms that link excess body fat to cancer risk as well as to understand the amount of weight loss needed for substantial cancer risk reduction. Finally, as we develop better understanding of the mediators of the effects of excess body fatness on cancer risk, we should identify pharmacologic interventions that target those mediators so that they can be used to complement weight loss in order to reduce cancer risk. PMID:25870250

  16. Morphogenesis and pattern formation in biological systems experiments and models

    CERN Document Server

    Noji, Sumihare; Ueno, Naoto; Maini, Philip

    2003-01-01

    A central goal of current biology is to decode the mechanisms that underlie the processes of morphogenesis and pattern formation. Concerned with the analysis of those phenomena, this book covers a broad range of research fields, including developmental biology, molecular biology, plant morphogenesis, ecology, epidemiology, medicine, paleontology, evolutionary biology, mathematical biology, and computational biology. In Morphogenesis and Pattern Formation in Biological Systems: Experiments and Models, experimental and theoretical aspects of biology are integrated for the construction and investigation of models of complex processes. This collection of articles on the latest advances by leading researchers not only brings together work from a wide spectrum of disciplines, but also provides a stepping-stone to the creation of new areas of discovery.

  17. Approximate bayesian parameter inference for dynamical systems in systems biology

    International Nuclear Information System (INIS)

    This paper proposes to use approximate instead of exact stochastic simulation algorithms for approximate Bayesian parameter inference of dynamical systems in systems biology. It first presents the mathematical framework for the description of systems biology models, especially from the aspect of a stochastic formulation as opposed to deterministic model formulations based on the law of mass action. In contrast to maximum likelihood methods for parameter inference, approximate inference method- share presented which are based on sampling parameters from a known prior probability distribution, which gradually evolves toward a posterior distribution, through the comparison of simulated data from the model to a given data set of measurements. The paper then discusses the simulation process, where an over- view is given of the different exact and approximate methods for stochastic simulation and their improvements that we propose. The exact and approximate simulators are implemented and used within approximate Bayesian parameter inference methods. Our evaluation of these methods on two tasks of parameter estimation in two different models shows that equally good results are obtained much faster when using approximate simulation as compared to using exact simulation. (Author)

  18. Building momentum for systems and synthetic biology in India

    OpenAIRE

    Krishnan, Remya; Manjaly-Antony, Lijo Anto; Dhar, Pawan K.

    2010-01-01

    Biological systems are inherently noisy. Predicting the outcome of a perturbation is extremely challenging. Traditional reductionist approach of describing properties of parts, vis-a-vis higher level behaviour has led to enormous understanding of fundamental molecular level biology. This approach typically consists of converting genes into junk (knock-down) and garbage (knock-out) and observe how a system responds. To enable broader understanding of biological dynamics, an integrated computat...

  19. Global optimization in systems biology: stochastic methods and their applications

    OpenAIRE

    Balsa-Canto, Eva; Banga, Julio R.; Egea, José A.; Villaverde, A. F.; Hijas-Liste, G. M.

    2012-01-01

    Mathematical optimization is at the core of many problems in systems biology: (1) as the underlying hypothesis for model development, (2) in model identification, or (3) in the computation of optimal stimulation procedures to synthetically achieve a desired biological behavior. These problems are usually formulated as nonlinear programing problems (NLPs) with dynamic and algebraic constraints. However the nonlinear and highly constrained nature of systems biology models, together with the usu...

  20. Evaluation of treatment response for breast cancer: are we entering the era of "biological complete remission"?

    Institute of Scientific and Technical Information of China (English)

    Li Bian; Tao Wang; Yi Liu; Hui-Qiang Zhang; Jin-Jie Song; Shao-Hua Zhang; Shi-Kai Wu; San-Tai Song; Ze-Fei Jiang

    2012-01-01

    Breast cancer is one of the most common malignancies in women.The post-operative recurrence and metastasis are the leading causes of breast cancer-related mortality.In this study,we tried to explore the role of circulating tumor cell (CTC) detection combination PET/CT technology evaluating the prognosis and treatment response of patients with breast cancer; meanwhile,we attempted to assess the concept of "biological complete remission" (bCR) in this regard.A 56-year-old patient with breast cancer (T2N1M1,stage Ⅳ left breast cancer,with metastasis to axillary lymph nodes and lungs) received 6 cycles of salvage treatment with albumin-bound paclitaxel plus capecitabine and trastuzumab.Then,she underwent CTC detection and PET/CT for efficacy evaluation.CTC detection combination PET/CT is useful for the evaluation of the biological efficacy of therapies for breast cancer.The bCR of the patient appeared earlier than the conventional clinical imaging complete remission and promised the histological (pathological) complete remission.The integrated application of the concepts including bCR,imageological CR,and histological CR can achieve the early and accurate assessment of biological therapeutic reponse and prognosis of breast cancer.

  1. Systems biology in aging: linking the old and the young.

    Science.gov (United States)

    Hou, Lei; Huang, Jialiang; Green, Christopher D; Boyd-Kirkup, Jerome; Zhang, Wei; Yu, Xiaoming; Gong, Wenxuan; Zhou, Bing; Han, Jing-Dong J

    2012-11-01

    Aging can be defined as a process of progressive decline in the physiological capacity of an organism, manifested by accumulated alteration and destabilization at the whole system level. Systems biology approaches offer a promising new perspective to examine the old problem of aging. We begin this review by introducing the concepts of systems biology, and then illustrate the application of systems biology approaches to aging research, from gene expression profiling to network analysis. We then introduce the network that can be constructed using known lifespan and aging regulators, and conclude with a look forward to the future of systems biology in aging research. In summary, systems biology is not only a young field that may help us understand aging at a higher level, but also an important platform that can link different levels of knowledge on aging, moving us closer to a more comprehensive control of systematic decline during aging. PMID:23633915

  2. Review and application of group theory to molecular systems biology

    Directory of Open Access Journals (Sweden)

    Rietman Edward A

    2011-06-01

    Full Text Available Abstract In this paper we provide a review of selected mathematical ideas that can help us better understand the boundary between living and non-living systems. We focus on group theory and abstract algebra applied to molecular systems biology. Throughout this paper we briefly describe possible open problems. In connection with the genetic code we propose that it may be possible to use perturbation theory to explore the adjacent possibilities in the 64-dimensional space-time manifold of the evolving genome. With regards to algebraic graph theory, there are several minor open problems we discuss. In relation to network dynamics and groupoid formalism we suggest that the network graph might not be the main focus for understanding the phenotype but rather the phase space of the network dynamics. We show a simple case of a C6 network and its phase space network. We envision that the molecular network of a cell is actually a complex network of hypercycles and feedback circuits that could be better represented in a higher-dimensional space. We conjecture that targeting nodes in the molecular network that have key roles in the phase space, as revealed by analysis of the automorphism decomposition, might be a better way to drug discovery and treatment of cancer.

  3. Review and application of group theory to molecular systems biology.

    Science.gov (United States)

    Rietman, Edward A; Karp, Robert L; Tuszynski, Jack A

    2011-01-01

    In this paper we provide a review of selected mathematical ideas that can help us better understand the boundary between living and non-living systems. We focus on group theory and abstract algebra applied to molecular systems biology. Throughout this paper we briefly describe possible open problems. In connection with the genetic code we propose that it may be possible to use perturbation theory to explore the adjacent possibilities in the 64-dimensional space-time manifold of the evolving genome. With regards to algebraic graph theory, there are several minor open problems we discuss. In relation to network dynamics and groupoid formalism we suggest that the network graph might not be the main focus for understanding the phenotype but rather the phase space of the network dynamics. We show a simple case of a C6 network and its phase space network. We envision that the molecular network of a cell is actually a complex network of hypercycles and feedback circuits that could be better represented in a higher-dimensional space. We conjecture that targeting nodes in the molecular network that have key roles in the phase space, as revealed by analysis of the automorphism decomposition, might be a better way to drug discovery and treatment of cancer. PMID:21696623

  4. The molecular biology of cancer and its diagnostic implications.

    Science.gov (United States)

    Aw, S E

    1981-07-01

    The origin of cancer is discussed from the view of the two-stage model of malignant transformation. Environmental carcinogens play an integral part in the process. When the cell is transformed, cell surface changes are found for such components as fibronectin, collagen, actin, myosin, glycopeptides and enzyme activities. Hormone receptors are a fruitful line for research. Both qualitative and quantitative alterations are also seen with cancer cell enzymes. Among enzymes that can be used as markers of malignancy are the protease. A group of oncodevelopmental proteins, hormonal and non-hormonal, are in regular service for the management of cancer. Improvements in diagnostic specificity can be expected as the newer technologies are harnessed for medical use.

  5. Systems biology of neutrophil differentiation and immune response

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

    2005-01-01

    Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies...

  6. Systems Biology Strategy Reveals PKC-delta is Key for Sensitizing TRAIL-Resistant Human Fibrosarcoma

    Directory of Open Access Journals (Sweden)

    Kentaro eHayashi

    2015-01-01

    Full Text Available Cancer cells are highly variable and resistant to therapeutic intervention. Recently, the use of the tumor necrosis factor related apoptosis-inducing ligand (TRAIL induced treatment is gaining momentum, due to TRAIL’s ability to specifically target cancers with limited effect on normal cells. However, several malignant cancer types still remain non-sensitive to TRAIL. Previously, we developed a dynamic computational model, based on perturbation-response approach, and predicted protein kinase C (PKC as the most effective target, with over 95% capacity to kill human fibrosarcoma (HT1080 in TRAIL stimulation (Piras, V. et al. 2011, Scientific Reports. Here, to validate the model prediction, which has significant implications for cancer treatment, we conducted experiments on two TRAIL-resistant cancer cell lines (HT1080 and HT29. Using PKC inhibitor Bisindolylmaleimide I, we first demonstrate, as predicted by our previous model, cell viability is significantly impaired with over 95% death of both cancer types. Next, to identify crucial PKC isoform from 10 known members, we analyzed their mRNA expressions in HT1080 cells and shortlisted 4 isoforms for siRNA knock-down (KD experiments. From these KDs, PKC-delta produced the most cancer cell death in conjunction with TRAIL. Overall, systems biology approach, combining model prediction with experimental validation, holds promise for TRAIL-based cancer therapy.

  7. Biological oceanography of the red oceanic system

    Science.gov (United States)

    Theil, Hjalmar; Weikert, Horst

    1. In 1977, 1979 and 1980-81, investigations were carried out which aimed at evaluating the potential risks from mining metalliferous muds precipating in the Atlantis II Deep of the central Red Sea. This environmental research was initiated by the Saudi Sudanese Red Sea Joint Commission in order to avoid any danger for the Red Sea ecosystem. The broad environmental research programme coherent studies in physical, chemical, biological, and geological oceanography as well as toxicological investigations in the oceanic and in reef zones. We summarise the results from our biological fiels studies in the open sea. 2. The biological investigations were concentrated on the area of the Atlantis II Deep. Benthos was sampled between 700-2000m. For comparison a few samples were also taken further north in the central Red Sea, and to east and west along the flanking deep terraces (500-1000m). Plankton studies covered the total water column above the Deep, and were extended along the axial through to north and south. 3. Benthos sampling was carried out using a heavy closing trawl, a large box grab (box size 50 × 50 cm), Van Veen grabs and traps; photographic surveys were made a phototrap and a photosled. Community respiration was measured with a ship-board method using grab subsamples. Nutrient concentrations, seston and phytoplankton standing stocks as well as in situ primary production were determined from hydrocast samples. Data on zooplankton and micronekton composition and standing stock were obtained from samples collected using different multiple opening-and-closing nets equipped with 100 μm, 300 μm, and 1000 μm mesh sizes. Daily and ontogenetical vertical migration patterns were studied by comparisons of data from midday and midnight tows. 4. Throughout the whole area the sediment is a pteropod ooze containing low contentrations of organic matter; measured organic carbon and nitrogen contents were 0.5 and 0.05% respectively, and chloroplastic pigment equivalents

  8. A data integration approach for cell cycle analysis oriented to model simulation in systems biology

    Directory of Open Access Journals (Sweden)

    Mosca Ettore

    2007-08-01

    Full Text Available Abstract Background The cell cycle is one of the biological processes most frequently investigated in systems biology studies and it involves the knowledge of a large number of genes and networks of protein interactions. A deep knowledge of the molecular aspect of this biological process can contribute to making cancer research more accurate and innovative. In this context the mathematical modelling of the cell cycle has a relevant role to quantify the behaviour of each component of the systems. The mathematical modelling of a biological process such as the cell cycle allows a systemic description that helps to highlight some features such as emergent properties which could be hidden when the analysis is performed only from a reductionism point of view. Moreover, in modelling complex systems, a complete annotation of all the components is equally important to understand the interaction mechanism inside the network: for this reason data integration of the model components has high relevance in systems biology studies. Description In this work, we present a resource, the Cell Cycle Database, intended to support systems biology analysis on the Cell Cycle process, based on two organisms, yeast and mammalian. The database integrates information about genes and proteins involved in the cell cycle process, stores complete models of the interaction networks and allows the mathematical simulation over time of the quantitative behaviour of each component. To accomplish this task, we developed, a web interface for browsing information related to cell cycle genes, proteins and mathematical models. In this framework, we have implemented a pipeline which allows users to deal with the mathematical part of the models, in order to solve, using different variables, the ordinary differential equation systems that describe the biological process. Conclusion This integrated system is freely available in order to support systems biology research on the cell cycle and

  9. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  10. The Current State and Perspectives of Systems Biology

    Institute of Scientific and Technical Information of China (English)

    Tielui Shi; Yixue Li

    2006-01-01

    Emerging as a new field in biology recently, Systems Biology provides a branch new way to study the biological activities in organisms. In order to decode the complexity of life systematically,systems biology integrates the "-omics" and uses the high throughput methods from transcriptomics,protomics and metabonomics to detect the dynamic activities in cell; and then, it incorporates bioinformatics methods to integrate and analyze those data, and simulate the biological processes based on the model built from those integrated data. In this paper, the current state, the research field and the methods for the Systems Biology are introduced briefly, and then, several ideas about future development in this field are also proposed.

  11. Primo Vascular System: A Unique Biological System Shifting a Medical Paradigm.

    Science.gov (United States)

    Chikly, Bruno; Roberts, Paul; Quaghebeur, Jörgen

    2016-01-01

    The primo vascular system has a specific anatomical and immunohistochemical signature that sets it apart from the arteriovenous and lymphatic systems. With immune and endocrine functions, the primo vascular system has been found to play a large role in biological processes, including tissue regeneration, inflammation, and cancer metastases. Although scientifically confirmed in 2002, the original discovery was made in the early 1960s by Bong-Han Kim, a North Korean scientist. It would take nearly 40 years after that discovery for scientists to revisit Kim's research to confirm the early findings. The presence of primo vessels in and around blood and lymph vessels, nerves, viscera, and fascia, as well as in the brain and spinal cord, reveals a common link that could potentially open novel possibilities of integration with cranial, lymphatic, visceral, and fascial approaches in manual medicine. PMID:26745560

  12. Tracing organizing principles: Learning from the history of systems biology

    DEFF Research Database (Denmark)

    Green, Sara; Wolkenhauer, Olaf

    2014-01-01

    With the emergence of systems biology, the identification of organizing principles is being highlighted as a key research aim. Researchers attempt to “reverse engineer” the functional organization of biological systems using methodologies from mathematics, engineering and computer science while...... taking advantage of data produced by new experimental techniques. While systems biology is a relatively new approach, the quest for general principles of biological organization dates back to systems theoretic approaches in early and mid-twentieth century. The aim of this paper is to draw...... on this historical background in order to increase the understanding of the motivation behind the search for general principles and to clarify different epistemic aims within systems biology. We pinpoint key aspects of earlier approaches that also underlie the current practice. These are i) the focus on relational...

  13. Mathematical modeling of the evolution of a simple biological system

    Digital Repository Service at National Institute of Oceanography (India)

    Gonsalves, M.J.B.D.; Neetu, S.; Krishnan, K.P.; Attri, K.; LokaBharathi, P.A.

    physical system, where a model usually can be developed from well established fundamental principles, in case of biological systems such principles are not always available offering an opportunity for innovation. The success of the innovation, of course...

  14. Systems biology of cisplatin resistance: past, present and future.

    Science.gov (United States)

    Galluzzi, L; Vitale, I; Michels, J; Brenner, C; Szabadkai, G; Harel-Bellan, A; Castedo, M; Kroemer, G

    2014-01-01

    The platinum derivative cis-diamminedichloroplatinum(II), best known as cisplatin, is currently employed for the clinical management of patients affected by testicular, ovarian, head and neck, colorectal, bladder and lung cancers. For a long time, the antineoplastic effects of cisplatin have been fully ascribed to its ability to generate unrepairable DNA lesions, hence inducing either a permanent proliferative arrest known as cellular senescence or the mitochondrial pathway of apoptosis. Accumulating evidence now suggests that the cytostatic and cytotoxic activity of cisplatin involves both a nuclear and a cytoplasmic component. Despite the unresolved issues regarding its mechanism of action, the administration of cisplatin is generally associated with high rates of clinical responses. However, in the vast majority of cases, malignant cells exposed to cisplatin activate a multipronged adaptive response that renders them less susceptible to the antiproliferative and cytotoxic effects of the drug, and eventually resume proliferation. Thus, a large fraction of cisplatin-treated patients is destined to experience therapeutic failure and tumor recurrence. Throughout the last four decades great efforts have been devoted to the characterization of the molecular mechanisms whereby neoplastic cells progressively lose their sensitivity to cisplatin. The advent of high-content and high-throughput screening technologies has accelerated the discovery of cell-intrinsic and cell-extrinsic pathways that may be targeted to prevent or reverse cisplatin resistance in cancer patients. Still, the multifactorial and redundant nature of this phenomenon poses a significant barrier against the identification of effective chemosensitization strategies. Here, we discuss recent systems biology studies aimed at deconvoluting the complex circuitries that underpin cisplatin resistance, and how their findings might drive the development of rational approaches to tackle this clinically relevant

  15. Surgery and radiation therapy of triple-negative breast cancers: From biology to clinics.

    Science.gov (United States)

    Bernier, Jacques; Poortmans, Philip M P

    2016-08-01

    Triple negative breast cancer refers to tumours lacking the expression of the three most used tumour markers, namely oestrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). These cancers are known to carry a more dismal prognosis than the other molecular subtypes. Whether a more aggressive local-regional treatment is warranted or not in patients with triple-negative breast cancer is still a matter of debate. Indeed there remain a number of grey zones with respect to the optimization of the extent and the timing of surgery and radiation therapy (RT) in this patient population, also in consideration of the significant heterogeneity in biological behaviour and response to treatment identified for these tumours. The objective of this review is to provide an insight into the biological and clinical behaviour of triple-negative breast cancers and revisit the most recent advances in their management, focussing on local-regional treatments. PMID:27318170

  16. Telomerase and telomeres : From basic biology to cancer treatment

    NARCIS (Netherlands)

    Helder, MN; Wisman, GBA; van der Zee, AGJ

    2002-01-01

    The limited capacity to divide is one of the major differences between normal somatic cells and cancerous cells. This finite life span' of somatic cells is closely linked to loss of telomeric DNA at telomeres, the 'chromosome caps' consisting of repeated (TTAGGG) sequences. In more than 85% of advan

  17. Clinical and biological characteristics of colorectal cancer with familial predisposition

    Institute of Scientific and Technical Information of China (English)

    WU Bao-ping; ZHANG Ya-li; ZHOU Dian-yuan; GAO Chun-fang; LAI Zhuo-sheng

    2001-01-01

    To evaluate the microsatellite instability (MSI), expression of mismatch repair (MMR) gene (hMLH1, hMSH2) and proliferation kinetics in colorectal cancer (CRC) with familial predisposition. Method:Forty-six cases of CRC were studied using silver staining polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique, streptavidin-peroxidase (SP) immunohistochemical method and flow cytometry. Results: In CRC patients with familial predisposition, the MSI-positive rate was higher than in sporadic CRC (P<0.05). Familial predisposition and positive MSI were strongly related to early age of cancer onset, the proclivity for proximal colonic cancer, poor differentiated and extracolorectaln malignancies (P<0.01, P<0.05). The incidence of negative expression ofhMLH1 in tumor tissue and hMLH1, hMSH2 in normal colorectal tissues was significantly higher (P<0.05). The negative expression of hMLH1 together with hMSH2 was related with positive MSI (P<0.05).In MSI-positive CRC cells, the proliferation cell nucleus antigen (PCNA) expression, proliferation index and S-phase cells decreased obviously (P<0.01, P<0.05). Conclusion: In CRC with familial predisposition, MSI might be an important contributor. The rate ofhMLH1 and hMSH2 mutation increased in tumor and normal tissue, and the proliferation activity of their cancer cell was lower.

  18. Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints

    OpenAIRE

    Cacao, Eliedonna; Hada, Megumi; Saganti, Premkumar B.; George, Kerry A.; Francis A Cucinotta

    2016-01-01

    The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrog...

  19. The Prognostic Significance of Apoptosis-Related Biological Markers in Chinese Gastric Cancer Patients

    OpenAIRE

    Liu, Xiaowen; Cai, Hong; Huang, Hua; Long, Ziwen; Shi, Yingqiang; Wang, Yanong

    2011-01-01

    Background and Objective The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as p53, bcl-2, bax, and c-myc, and clinicopathological features and their prognostic value. Methods From 1996 to 2007, 4426 patients had undergone curative D2 gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 5...

  20. The influence of race and ethnicity on the biology of cancer.

    Science.gov (United States)

    Henderson, Brian E; Lee, Norman H; Seewaldt, Victoria; Shen, Hongbing

    2012-09-01

    It is becoming clear that some of the differences in cancer risk, incidence and survival among people of different racial and ethnic backgrounds can be attributed to biological factors. However, identifying these factors and exploiting them to help eliminate cancer disparities has proved challenging. With this in mind, we asked four scientists for their opinions on the most crucial advances, as well as the challenges and what the future holds for this important emerging area of research.

  1. The Systems Biology Research Tool: evolvable open-source software

    Directory of Open Access Journals (Sweden)

    Wright Jeremiah

    2008-06-01

    Full Text Available Abstract Background Research in the field of systems biology requires software for a variety of purposes. Software must be used to store, retrieve, analyze, and sometimes even to collect the data obtained from system-level (often high-throughput experiments. Software must also be used to implement mathematical models and algorithms required for simulation and theoretical predictions on the system-level. Results We introduce a free, easy-to-use, open-source, integrated software platform called the Systems Biology Research Tool (SBRT to facilitate the computational aspects of systems biology. The SBRT currently performs 35 methods for analyzing stoichiometric networks and 16 methods from fields such as graph theory, geometry, algebra, and combinatorics. New computational techniques can be added to the SBRT via process plug-ins, providing a high degree of evolvability and a unifying framework for software development in systems biology. Conclusion The Systems Biology Research Tool represents a technological advance for systems biology. This software can be used to make sophisticated computational techniques accessible to everyone (including those with no programming ability, to facilitate cooperation among researchers, and to expedite progress in the field of systems biology.

  2. Machine learning in systems biology at different scales : from molecular biology to ecology

    OpenAIRE

    Aderhold, Andrej

    2015-01-01

    Machine learning has been a source for continuous methodological advances in the field of computational learning from data. Systems biology has profited in various ways from machine learning techniques but in particular from network inference, i.e. the learning of interactions given observed quantities of the involved components or data that stem from interventional experiments. Originally this domain of system biology was confined to the inference of gene regulation networks but ...

  3. Integrating biological knowledge into variable selection: an empirical Bayes approach with an application in cancer biology

    OpenAIRE

    Hill Steven M; Neve Richard M; Bayani Nora; Kuo Wen-Lin; Ziyad Safiyyah; Spellman Paul T; Gray Joe W; Mukherjee Sach

    2012-01-01

    Abstract Background An important question in the analysis of biochemical data is that of identifying subsets of molecular variables that may jointly influence a biological response. Statistical variable selection methods have been widely used for this purpose. In many settings, it may be important to incorporate ancillary biological information concerning the variables of interest. Pathway and network maps are one example of a source of such information. However, although ancillary informatio...

  4. Molecular biology of cancer-associated fibroblasts: can these cells be targeted in anti-cancer therapy?

    Science.gov (United States)

    Gonda, Tamas A; Varro, Andrea; Wang, Timothy C; Tycko, Benjamin

    2010-02-01

    It is increasingly recognized that the non-neoplastic stromal compartment in most solid cancers plays an active role in tumor proliferation, invasion and metastasis. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types in the tumor stroma, and these cells are pro-tumorigenic. Evidence that CAFs are epigenetically and possibly also genetically distinct from normal fibroblasts is beginning to define these cells as potential targets of anti-cancer therapy. Here, we review the cell-of-origin and molecular biology of CAFs, arguing that such knowledge provides a rational basis for designing therapeutic strategies to coordinately and synergistically target both the stromal and malignant epithelial component of human cancers.

  5. Integrative systems biology for data-driven knowledge discovery.

    Science.gov (United States)

    Greene, Casey S; Troyanskaya, Olga G

    2010-09-01

    Integrative systems biology is an approach that brings together diverse high-throughput experiments and databases to gain new insights into biological processes or systems at molecular through physiological levels. These approaches rely on diverse high-throughput experimental techniques that generate heterogeneous data by assaying varying aspects of complex biological processes. Computational approaches are necessary to provide an integrative view of these experimental results and enable data-driven knowledge discovery. Hypotheses generated from these approaches can direct definitive molecular experiments in a cost-effective manner. By using integrative systems biology approaches, we can leverage existing biological knowledge and large-scale data to improve our understanding of as yet unknown components of a system of interest and how its malfunction leads to disease.

  6. Magnetic biosensor system to detect biological targets

    KAUST Repository

    Li, Fuquan

    2012-09-01

    Magneto-resistive sensors in combination with magnetic beads provide sensing platforms, which are small in size and highly sensitive. These platforms can be fully integrated with microchannels and electronics to enable devices capable of performing complex tasks. Commonly, a sandwich method is used that requires a specific coating of the sensor\\'s surface to immobilize magnetic beads and biological targets on top of the sensor. This paper concerns a micro device to detect biological targets using magnetic concentration, magnetic as well as mechanical trapping and magnetic sensing. Target detection is based on the size difference between bare magnetic beads and magnetic beads with targets attached. This method remedies the need for a coating layer and reduces the number of steps required to run an experiment. © 2012 IEEE.

  7. An update on the biology of cancer stem cells in breast cancer.

    Science.gov (United States)

    García Bueno, José María; Ocaña, Alberto; Castro-García, Paola; Gil Gas, Carmen; Sánchez-Sánchez, Francisco; Poblet, Enrique; Serrano, Rosario; Calero, Raúl; Ramírez-Castillejo, Carmen

    2008-12-01

    Breast cancer stem cells are defined as cancer cells with self-renewal capacity. These cells represent a small subpopulation endowed with the ability to form new tumours when injected in nude mice. Markers of differentiation have been used to identify these cancer cells. In the case of breast cancer, CD44+/CD24- select a population with stem cell properties. The fact that these cells have self-renewal ability has suggested that this population could be responsible for new tumour formation and cancer relapse. These cells have been shown to be more resistant to chemotherapy and radiotherapy than normal cancer cells. The identification of the molecular druggable alterations responsible for the initiation and maintenance of cancer stem cells is an important goal. In this article we will review all these points with special emphasis on the possible role of new drugs designed to interact with molecular pathways of cancer stem cells.

  8. Measuring cell identity in noisy biological systems

    OpenAIRE

    Birnbaum, Kenneth D; Kussell, Edo

    2011-01-01

    Global gene expression measurements are increasingly obtained as a function of cell type, spatial position within a tissue and other biologically meaningful coordinates. Such data should enable quantitative analysis of the cell-type specificity of gene expression, but such analyses can often be confounded by the presence of noise. We introduce a specificity measure Spec that quantifies the information in a gene's complete expression profile regarding any given cell type, and an uncertainty me...

  9. Towards systems thinking in cell biology education

    OpenAIRE

    Verhoeff, Roald Pieter

    2003-01-01

    Students are taught a large variety of life structures and processes at the cellular level. The concepts used to describe them are mainly drawn from the sub-cellular level, but this knowledge seems to be fragmentary if its integration at the cellular and organismic level remains undone. As a consequence, many students fail to acquire coherent conceptual understanding of the cell as a basic and functional unit of the organism. To enhance the coherence in students’ cell biological knowledge we ...

  10. Systems for Detection and Identification of Biological Aerosols (Review Paper)

    OpenAIRE

    Eva Švabenska

    2012-01-01

    Easy and inexpensive manufacturing of biological weapons, their complicated detection, expensive protection, difficult treating of affected individuals, selective impact only for people, animals or plants, are all factors making an effective defense against biological warfare agents very difficult. The aim of this study is an introduction to the systems for the detection and identification of biological aerosols containing dangerous bioagents. The basic techniques used for detection and ident...

  11. Progress of transcription factor Twist expression in breast cancer and its biological effect

    Institute of Scientific and Technical Information of China (English)

    Tian Qian

    2016-01-01

    Breast cancer is the most common malignant tumor in women and the pathogenesis is not fully elucidated. Proliferation, invasion, epithelial-mesenchymal transition and angiogenesis are the links closely related to the occurrence and development of breast cancer. Twist is a type of basic helix-loop-helix transcription factor that can affect cell proliferation and invasion process, epithelial-mesenchymal transition process and angiogenesis process through regulating the transcription of downstream target genes. In the research, the study of transcription factor Twist expression in breast cancer and its biological effect is reviewed.

  12. Connecting Genomic Alterations to Cancer Biology with Proteomics: The NCI Clinical Proteomic Tumor Analysis Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, Matthew; Gillette, Michael; Carr, Steven A.; Paulovich, Amanda G.; Smith, Richard D.; Rodland, Karin D.; Townsend, Reid; Kinsinger, Christopher; Mesri, Mehdi; Rodriguez, Henry; Liebler, Daniel

    2013-10-03

    The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium is applying the latest generation of proteomic technologies to genomically annotated tumors from The Cancer Genome Atlas (TCGA) program, a joint initiative of the NCI and the National Human Genome Research Institute. By providing a fully integrated accounting of DNA, RNA, and protein abnormalities in individual tumors, these datasets will illuminate the complex relationship between genomic abnormalities and cancer phenotypes, thus producing biologic insights as well as a wave of novel candidate biomarkers and therapeutic targets amenable to verifi cation using targeted mass spectrometry methods.

  13. Advanced pancreatic cancer: flourishing novel approaches in the era of biological therapy.

    Science.gov (United States)

    Chiu, Joanne W; Wong, Hilda; Leung, Roland; Pang, Roberta; Cheung, Tan-To; Fan, Sheung-Tat; Poon, Ronnie; Yau, Thomas

    2014-09-01

    The progress in the development of systemic treatment for advanced pancreatic cancer (APC) has been slow. The mainstream treatment remains using chemotherapy including gemcitabine, FOLFIRINOX, and nab-paclitaxel. Erlotinib is the only approved biological therapy with marginal benefit. Studies of agents targeting epidermal growth factor receptor, angiogenesis, and RAS signaling have not been satisfying, and the usefulness of targeted therapy in APC is uncertain. Understanding in molecular processes and tumor biology has opened the door for new treatment strategies such as targeting insulin-like growth factor 1 receptor, transforming growth factor β, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Notch pathway. New directions also include the upcoming immunotherapy and many novel agents that act on the microenvironment. The practice of personalized medicine using predictive biomarkers and pharmacogenomics signatures may also enhance the effectiveness of existing treatment. Future treatment approaches may involve comprehensive genomic assessment of tumor and integrated combinations of multiple agents to overcome treatment resistance. PMID:25117068

  14. Proteomics-Based Analysis of Protein Complexes in Pluripotent Stem Cells and Cancer Biology.

    Science.gov (United States)

    Sudhir, Putty-Reddy; Chen, Chung-Hsuan

    2016-01-01

    A protein complex consists of two or more proteins that are linked together through protein-protein interactions. The proteins show stable/transient and direct/indirect interactions within the protein complex or between the protein complexes. Protein complexes are involved in regulation of most of the cellular processes and molecular functions. The delineation of protein complexes is important to expand our knowledge on proteins functional roles in physiological and pathological conditions. The genetic yeast-2-hybrid method has been extensively used to characterize protein-protein interactions. Alternatively, a biochemical-based affinity purification coupled with mass spectrometry (AP-MS) approach has been widely used to characterize the protein complexes. In the AP-MS method, a protein complex of a target protein of interest is purified using a specific antibody or an affinity tag (e.g., DYKDDDDK peptide (FLAG) and polyhistidine (His)) and is subsequently analyzed by means of MS. Tandem affinity purification, a two-step purification system, coupled with MS has been widely used mainly to reduce the contaminants. We review here a general principle for AP-MS-based characterization of protein complexes and we explore several protein complexes identified in pluripotent stem cell biology and cancer biology as examples. PMID:27011181

  15. Cancer risk in systemic lupus

    DEFF Research Database (Denmark)

    Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Labrecque, Jeremy;

    2013-01-01

    .46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0......: These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus......OBJECTIVE: To update estimates of cancer risk in SLE relative to the general population. METHODS: A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. RESULTS: Across 30...

  16. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Renal Cell) Cancer Leukemia Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer All ... Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & Early Detection Treatment Cancer & Public Health Cancer ...

  17. Evolutionary Tradeoffs between Economy and Effectiveness in Biological Homeostasis Systems

    OpenAIRE

    Pablo Szekely; Hila Sheftel; Avi Mayo; Uri Alon

    2013-01-01

    Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical. For example, regulatory systems that are designed to repair damage must be effective in reducing damage, but economical in not making too many repair proteins because making excessive proteins carries a fitness cost to the cell, called protein burden. In order to see how biological systems compromise between the two tasks of effectiveness and economy, we applied an approach ...

  18. Method And System For Examining Biological Materials Using Low Power Cw Excitation Raman Spectroscopy.

    Energy Technology Data Exchange (ETDEWEB)

    Alfano, Robert R. (Bronx, NY); Wang, Wubao (Flushing, NY)

    2003-05-06

    A method and system for examining biological materials using low-power cw excitation Raman spectroscopy. A low-power continuous wave (cw) pump laser beam and a low-power cw Stokes (or anti-Stokes) probe laser beam simultaneously illuminate a biological material and traverse the biological material in collinearity. The pump beam, whose frequency is varied, is used to induce Raman emission from the biological material. The intensity of the probe beam, whose frequency is kept constant, is monitored as it leaves the biological material. When the difference between the pump and probe excitation frequencies is equal to a Raman vibrational mode frequency of the biological material, the weak probe signal becomes amplified by one or more orders of magnitude (typically up to about 10.sup.4 -10.sup.6) due to the Raman emission from the pump beam. In this manner, by monitoring the intensity of the probe beam emitted from the biological material as the pump beam is varied in frequency, one can obtain an excitation Raman spectrum for the biological material tested. The present invention may be applied to in the in vivo and/or in vitro diagnosis of diabetes, heart disease, hepatitis, cancers and other diseases by measuring the characteristic excitation Raman lines of blood glucose, cholesterol, serum glutamic oxalacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT), tissues and other corresponding Raman-active body constituents, respectively.

  19. Tumor biology and cancer therapy – an evolving relationship

    OpenAIRE

    Lother Ulrike; Krndija Denis; Ahn Johann; Seufferlein Thomas; Adler Guido; von Wichert Götz

    2009-01-01

    Abstract The aim of palliative chemotherapy is to increase survival whilst maintaining maximum quality of life for the individual concerned. Although we are still continuing to explore the optimum use of traditional chemotherapy agents, the introduction of targeted therapies has significantly broadened the therapeutic options. Interestingly, the results from current trials put the underlying biological concept often into a new, less favorable perspective. Recent data suggested that altered pa...

  20. Systems-biology dissection of eukaryotic cell growth

    OpenAIRE

    Andrews Justen; Przytycka Teresa M

    2010-01-01

    Abstract A recent article in BMC Biology illustrates the use of a systems-biology approach to integrate data across the transcriptome, proteome and metabolome of budding yeast in order to dissect the relationship between nutrient conditions and cell growth. See research article http://jbiol.com/content/6/2/4 and http://www.biomedcentral.com/1741-7007/8/68

  1. Systems Biology: The elements and principles of Life

    NARCIS (Netherlands)

    Westerhoff, H.V.; Winder, C.; Messiha, H.; Simeonidis, E.; Adamczyk, M.; Verma, M.; Bruggeman, F.J.; Dunn, W.

    2009-01-01

    Systems Biology has a mission that puts it at odds with traditional paradigms of physics and molecular biology, such as the simplicity requested by Occam’s razor and minimum energy/maximal efficiency. By referring to biochemical experiments on control and regulation, and on flux balancing in yeast,

  2. Systems biology by the rules: hybrid intelligent systems for pathway modeling and discovery

    Directory of Open Access Journals (Sweden)

    Bosl William J

    2007-02-01

    Full Text Available Abstract Background Expert knowledge in journal articles is an important source of data for reconstructing biological pathways and creating new hypotheses. An important need for medical research is to integrate this data with high throughput sources to build useful models that span several scales. Researchers traditionally use mental models of pathways to integrate information and development new hypotheses. Unfortunately, the amount of information is often overwhelming and these are inadequate for predicting the dynamic response of complex pathways. Hierarchical computational models that allow exploration of semi-quantitative dynamics are useful systems biology tools for theoreticians, experimentalists and clinicians and may provide a means for cross-communication. Results A novel approach for biological pathway modeling based on hybrid intelligent systems or soft computing technologies is presented here. Intelligent hybrid systems, which refers to several related computing methods such as fuzzy logic, neural nets, genetic algorithms, and statistical analysis, has become ubiquitous in engineering applications for complex control system modeling and design. Biological pathways may be considered to be complex control systems, which medicine tries to manipulate to achieve desired results. Thus, hybrid intelligent systems may provide a useful tool for modeling biological system dynamics and computational exploration of new drug targets. A new modeling approach based on these methods is presented in the context of hedgehog regulation of the cell cycle in granule cells. Code and input files can be found at the Bionet website: www.chip.ord/~wbosl/Software/Bionet. Conclusion This paper presents the algorithmic methods needed for modeling complicated biochemical dynamics using rule-based models to represent expert knowledge in the context of cell cycle regulation and tumor growth. A notable feature of this modeling approach is that it allows biologists

  3. Directed evolution and synthetic biology applications to microbial systems.

    Science.gov (United States)

    Bassalo, Marcelo C; Liu, Rongming; Gill, Ryan T

    2016-06-01

    Biotechnology applications require engineering complex multi-genic traits. The lack of knowledge on the genetic basis of complex phenotypes restricts our ability to rationally engineer them. However, complex phenotypes can be engineered at the systems level, utilizing directed evolution strategies that drive whole biological systems toward desired phenotypes without requiring prior knowledge of the genetic basis of the targeted trait. Recent developments in the synthetic biology field accelerates the directed evolution cycle, facilitating engineering of increasingly complex traits in biological systems. In this review, we summarize some of the most recent advances in directed evolution and synthetic biology that allows engineering of complex traits in microbial systems. Then, we discuss applications that can be achieved through engineering at the systems level. PMID:27054950

  4. Immunglobulin Expression and Its Biological Significance in Cancer Cells

    Institute of Scientific and Technical Information of China (English)

    Duosha Hu; Hui Zheng; Haidan Liu; Ming Li; Wei Ren; Wei Liao; Zhi Duan; Lili Li; Ya Cao

    2008-01-01

    It is generally believed that the expression of a gene iS restricted "within the right place and at the right time".This principle has long been considered applicable as well to the expression of immunoglobulin(Ig)lymphocytes of B cell lineage.However,increasing evidence has shown Ig "paradoxically" expressed in malignant tumors of epitheliaI origin.We reviewed the recent progress in the study of cancer-derived Ig,and also discussed its mechanisms and possible functions,trying to arouse interest and attention to those working in the field of immunology and oncology.

  5. Search for organising principles: understanding in systems biology.

    Science.gov (United States)

    Mesarovic, M D; Sreenath, S N; Keene, J D

    2004-06-01

    Due in large measure to the explosive progress in molecular biology, biology has become arguably the most exciting scientific field. The first half of the 21st century is sometimes referred to as the 'era of biology', analogous to the first half of the 20th century, which was considered to be the 'era of physics'. Yet, biology is facing a crisis--or is it an opportunity--reminiscent of the state of biology in pre-double-helix time. The principal challenge facing systems biology is complexity. According to Hood, 'Systems biology defines and analyses the interrelationships of all of the elements in a functioning system in order to understand how the system works.' With 30000+ genes in the human genome the study of all relationships simultaneously becomes a formidably complex problem. Hanahan and Weinberg raised the question as to whether progress will consist of 'adding further layers of complexity to a scientific literature that is already complex almost beyond measure' or whether the progress will lead to a 'science with a conceptual structure and logical coherence that rivals that of chemistry or physics.' At the core of the challenge is the need for a new approach, a shift from reductionism to a holistic perspective. However, more than just a pronouncement of a new approach is needed. We suggest that what is needed is to provide a conceptual framework for systems biology research. We propose that the concept of a complex system, i.e. a system of systems as defined in mathematical general systems theory (MGST), is central to provide such a framework. We further argue that for a deeper understanding in systems biology investigations should go beyond building numerical mathematical or computer models--important as they are. Biological phenomena cannot be predicted with the level of numerical precision as in classical physics. Explanations in terms of how the categories of systems are organised to function in ever changing conditions are more revealing. Non

  6. Search for organising principles: understanding in systems biology.

    Science.gov (United States)

    Mesarovic, M D; Sreenath, S N; Keene, J D

    2004-06-01

    Due in large measure to the explosive progress in molecular biology, biology has become arguably the most exciting scientific field. The first half of the 21st century is sometimes referred to as the 'era of biology', analogous to the first half of the 20th century, which was considered to be the 'era of physics'. Yet, biology is facing a crisis--or is it an opportunity--reminiscent of the state of biology in pre-double-helix time. The principal challenge facing systems biology is complexity. According to Hood, 'Systems biology defines and analyses the interrelationships of all of the elements in a functioning system in order to understand how the system works.' With 30000+ genes in the human genome the study of all relationships simultaneously becomes a formidably complex problem. Hanahan and Weinberg raised the question as to whether progress will consist of 'adding further layers of complexity to a scientific literature that is already complex almost beyond measure' or whether the progress will lead to a 'science with a conceptual structure and logical coherence that rivals that of chemistry or physics.' At the core of the challenge is the need for a new approach, a shift from reductionism to a holistic perspective. However, more than just a pronouncement of a new approach is needed. We suggest that what is needed is to provide a conceptual framework for systems biology research. We propose that the concept of a complex system, i.e. a system of systems as defined in mathematical general systems theory (MGST), is central to provide such a framework. We further argue that for a deeper understanding in systems biology investigations should go beyond building numerical mathematical or computer models--important as they are. Biological phenomena cannot be predicted with the level of numerical precision as in classical physics. Explanations in terms of how the categories of systems are organised to function in ever changing conditions are more revealing. Non

  7. A system for success: BMC Systems Biology, a new open access journal

    OpenAIRE

    Webb Penelope A; Hodgkinson Matt J

    2007-01-01

    Abstract BMC Systems Biology is the first open access journal spanning the growing field of systems biology from molecules up to ecosystems. The journal has launched as more and more institutes are founded that are similarly dedicated to this new approach. BMC Systems Biology builds on the ongoing success of the BMC series, providing a venue for all sound research in the systems-level analysis of biology.

  8. A system for success: BMC Systems Biology, a new open access journal

    Directory of Open Access Journals (Sweden)

    Webb Penelope A

    2007-09-01

    Full Text Available Abstract BMC Systems Biology is the first open access journal spanning the growing field of systems biology from molecules up to ecosystems. The journal has launched as more and more institutes are founded that are similarly dedicated to this new approach. BMC Systems Biology builds on the ongoing success of the BMC series, providing a venue for all sound research in the systems-level analysis of biology.

  9. The magnitude of linear dichroism of biological tissues as a result of cancer changes

    Science.gov (United States)

    Bojchuk, T. M.; Yermolenko, S. B.; Fedonyuk, L. Y.; Petryshen, O. I.; Guminetsky, S. G.; Prydij, O. G.

    2012-01-01

    The results of studies of linear dichroism values of different types of biological tissues (human prostate, esophageal epithelial human muscle tissue in rats) both healthy and infected tumor at different stages of development are shown here. The significant differences in magnitude of linear dichroism and its spectral dependence in the spectral range λ = 330 - 750 nm both among the objects of study, and between biotissues: healthy (or affected by benign tumors) and cancer patients are established. It is researched that in all cases in biological tissues (prostate gland, esophagus, human muscle tissue in rats) with cancer the linear dichroism arises, the value of which depends on the type of tissue and time of the tumor process. As for healthy tissues linear dichroism is absent, the results may have diagnostic value for detecting and assessing the degree of development of cancer.

  10. Integrated physiology and systems biology of PPARα.

    Science.gov (United States)

    Kersten, Sander

    2014-07-01

    The Peroxisome Proliferator Activated Receptor alpha (PPARα) is a transcription factor that plays a major role in metabolic regulation. This review addresses the functional role of PPARα in intermediary metabolism and provides a detailed overview of metabolic genes targeted by PPARα, with a focus on liver. A distinction is made between the impact of PPARα on metabolism upon physiological, pharmacological, and nutritional activation. Low and high throughput gene expression analyses have allowed the creation of a comprehensive map illustrating the role of PPARα as master regulator of lipid metabolism via regulation of numerous genes. The map puts PPARα at the center of a regulatory hub impacting fatty acid uptake, fatty acid activation, intracellular fatty acid binding, mitochondrial and peroxisomal fatty acid oxidation, ketogenesis, triglyceride turnover, lipid droplet biology, gluconeogenesis, and bile synthesis/secretion. In addition, PPARα governs the expression of several secreted proteins that exert local and endocrine functions.

  11. Evaluation models for contaminated sites – biological system at risk

    OpenAIRE

    Golomeova, Mirjana; Krstev, Boris; Golomeov, Blagoj; Zendelska, Afrodita; Krstev, Aleksandar

    2009-01-01

    The paper presents the different methods that can be used correspond to three types of approaches, testing, monitoring, and modeling: experimental models, in situ indicators and mathematical models, and choice of model for contaminated sites – biological system at risk.

  12. Yeast systems biology to unravel the network of life

    DEFF Research Database (Denmark)

    Mustacchi, Roberta; Hohmann, S; Nielsen, Jens

    2006-01-01

    of advanced cell factories for production of fuels, chemicals, food ingredients and pharmaceuticals. The yeast Saccharomyces cerevisiae represents an excellent model system; the density of biological information available on this organism allows it to serve as a eukaryotic model for studying human diseases....... Furthermore, it serves as an industrial workhorse for production of a wide range of chemicals and pharmaceuticals. Systems biology involves the combination of novel experimental techniques from different disciplines as well as functional genomics, bioinformatics and mathematical modelling, and hence no single...... appropriate guidelines, establish an appropriate infrastructure for the network and organize courses, meetings and conferences that will consolidate the network and promote systems biology. This paper discusses the impacts of systems biology and how YSBN may play a role in the future development of the field...

  13. Advancing metabolic engineering through systems biology of industrial microorganisms.

    Science.gov (United States)

    Dai, Zongjie; Nielsen, Jens

    2015-12-01

    Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further.

  14. Advancing metabolic engineering through systems biology of industrial microorganisms

    DEFF Research Database (Denmark)

    Dai, Zongjie; Nielsen, Jens

    2015-01-01

    resources. The objective of systems biology is to gain a comprehensive and quantitative understanding of living cells and can hereby enhance our ability to characterize and predict cellular behavior. Systems biology of industrial microorganisms is therefore valuable for metabolic engineering. Here we review......Development of sustainable processes to produce bio-based compounds is necessary due to the severe environmental problems caused by the use of fossil resources. Metabolic engineering can facilitate the development of highly efficient cell factories to produce these compounds from renewable...... the application of systems biology tools for the identification of metabolic engineering targets which may lead to reduced development time for efficient cell factories. Finally, we present some perspectives of systems biology for advancing metabolic engineering further....

  15. Network benchmarking: a happy marriage between systems and synthetic biology.

    Science.gov (United States)

    Minty, Jeremy J; Varedi K, S Marjan; Nina Lin, Xiaoxia

    2009-03-27

    In their new Cell paper, Cantone et al. (2009) present exciting results on constructing and utilizing a small synthetic gene regulatory network in yeast that draws from two rapidly developing fields of systems and synthetic biology.

  16. [Molecular biology and childhood leukemia: E2A-PBX1 and central nervous system relapse].

    Science.gov (United States)

    Núñez-Enríquez, Juan Carlos; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. The inclusion of molecular biology techniques in the diagnosis and prognostic stratification of these patients has allowed major treatment achievements in developed countries. One of the best studied gene rearrangements is E2A-PBX1, which predicts isolated central nervous system relapse in patients with ALL. However, further research on the search for new molecular markers related to prognosis of patients with childhood leukemia is required. Such studies need the integration of different disciplines, including epidemiology. Epidemiological studies are needed not only to accelerate the discovery of new molecular markers and new biological signals as to the etiology and pathophysiology of cancer, but also to evaluate the clinical impact of these findings in well-defined populations. PMID:26509298

  17. Understanding the biology of cancer: has this any impact on treatment?

    Science.gov (United States)

    Desai, P B

    1994-01-01

    Rapid advances in laboratory techniques in the last two decades and, what is more important, in the last 5-7 years have significantly increased our knowledge and understanding on many fronts. We have learned much about (a) the basic biological processes of growth control and its aberrations, (b) the possible mechanisms involved in genetic initiation, progression and suppression, (c) the complexity of the multistep carcinogenesis induced by viruses, chemicals, hormones and other iatrogenic factors, (d) the secrets of immunological defence mechanisms and a host of other fundamental processes, (e) the application of molecular biology techniques to clinical problems, etc. The list is unending and often leads the uninitiated clinician to believe that the resolution of the mystery of the cancer cell and its successful control and cure are almost at hand. He or she often comes to believe that conventional principles in cancer treatment have radically changed from the 1960 and 1970 and that a new era in cancer treatment, based on our recent biological understanding, has already arrived. There is little doubt that the treatment scenario has changed significantly and that there is more hope for a cancer patient today than ever before-especially in certain types of paediatric and lymphoproliferative disorders; however, the unfortunate fact is that this cautiously optimistic therapeutic scenario has come about not because of any great understanding of the biological processes, which continue to confound us, but because of the intense interaction of various therapeutic disciplines and sophisticated technology now available for early diagnosis and more efficient therapeutic procedures in radiotherapy, chemotherapy and surgery. The author presents evidence and data here to show that, while treatment results have improved, we have a long way to go in understanding the biological processes before our knowledge can have a significant impact on the overall treatment methods in

  18. Effects of abiotic stress on plants: a systems biology perspective

    OpenAIRE

    Cramer Grant R; Urano Kaoru; Delrot Serge; Pezzotti Mario; Shinozaki Kazuo

    2011-01-01

    Abstract The natural environment for plants is composed of a complex set of abiotic stresses and biotic stresses. Plant responses to these stresses are equally complex. Systems biology approaches facilitate a multi-targeted approach by allowing one to identify regulatory hubs in complex networks. Systems biology takes the molecular parts (transcripts, proteins and metabolites) of an organism and attempts to fit them into functional networks or models designed to describe and predict the dynam...

  19. Stochastic chemical kinetics theory and (mostly) systems biological applications

    CERN Document Server

    Érdi, Péter

    2014-01-01

    This volume reviews the theory and simulation methods of stochastic kinetics by integrating historical and recent perspectives, presents applications, mostly in the context of systems biology and also in combustion theory. In recent years, due to the development in experimental techniques, such as optical imaging, single cell analysis, and fluorescence spectroscopy, biochemical kinetic data inside single living cells have increasingly been available. The emergence of systems biology brought renaissance in the application of stochastic kinetic methods.

  20. Biological effect of total lymphatic irradiation in cancer patients

    International Nuclear Information System (INIS)

    Fifteen cancer patients (1 with seminoma and 14 with malignant lymphoma) were given TLI(Total Lymphatic Irradiation) with 60Co γ-rays. Three cases received 6 Gy and 12 cases received 8 Gy, and the chromosome aberrations in peripheral blood lymphocytes were examined. It was estimated that a single TLI of 6 or 8 Gy would correspond to total body irradiation of averaged 3.78 or 4.3 Gy respectively. A course of moderate acute radiation symdrome with digestive tract reaction and hemopoietic and immunologic depession was observed clinically. WBC and platelets decreased rapidly. Lymphocytes changed both quantitatively and qualitatively at the early stage. Symptoms of acute radiation sickness subsided within 40 days. The severe complications were infection and hemorrhage. In the result, the tumours reduced in size or remitted completely. TLI seems to be a promising approach for the treatment of advenced malignant lymphomas. Further study of this treatment is needed

  1. The biology and function of exosomes in cancer.

    Science.gov (United States)

    Kalluri, Raghu

    2016-04-01

    Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40-150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients.

  2. The biology and function of exosomes in cancer.

    Science.gov (United States)

    Kalluri, Raghu

    2016-04-01

    Humans circulate quadrillions of exosomes at all times. Exosomes are a class of extracellular vesicles released by all cells, with a size range of 40-150 nm and a lipid bilayer membrane. Exosomes contain DNA, RNA, and proteins. Exosomes likely remove excess and/or unnecessary constituents from the cells, functioning like garbage bags, although their precise physiological role remains unknown. Additionally, exosomes may mediate specific cell-to-cell communication and activate signaling pathways in cells they fuse or interact with. Exosomes are detected in the tumor microenvironment, and emerging evidence suggests that they play a role in facilitating tumorigenesis by regulating angiogenesis, immunity, and metastasis. Circulating exosomes can be used as liquid biopsies and noninvasive biomarkers for early detection, diagnosis, and treatment of cancer patients. PMID:27035812

  3. Mathematical aspects of pattern formation in biological systems

    CERN Document Server

    Wei, Juncheng

    2013-01-01

    This monograph is concerned with the mathematical analysis of patterns which are encountered in biological systems. It summarises, expands and relates results obtained in the field during the last fifteen years. It also links the results to biological applications and highlights their relevance to phenomena in nature. Of particular concern are large-amplitude patterns far from equilibrium in biologically relevant models.The approach adopted in the monograph is based on the following paradigms:• Examine the existence of spiky steady states in reaction-diffusion systems and select as observabl

  4. Cancer: A Problem of Developmental Biology; Scientific Evidence for Reprogramming and Differentiation Therapy.

    Science.gov (United States)

    Sell, Stewart; Nicolini, Andrea; Ferrari, Paola; Biava, Pier M

    2016-01-01

    Current medical literature acknowledges that embryonic micro-environment is able to suppress tumor development. Administering carcinogenic substances during organogenesis in fact leads to embryonic malformations, but not to offspring tumor growth. Once organogenesis has ended, administration of carcinogenic substances causes a rise in offspring tumor development. These data indicate that cancer can be considered a deviation in normal development, which can be regulated by factors of the embryonic microenvironment. Furthermore, it has been demonstrated that teratoma differentiates into normal tissues once it is implanted in the embryo. Recently, it has been shown that implanting a melanoma in Zebrafish embryo did not result in a tumor development; however, it did in the adult specimen. This demonstrates that cancer cells can differentiate into normal tissues when implanted in the embryo. In addition, it was demonstrated that other tumors can revert into a normal phenotype and/or differentiate into normal tissue when implanted in the embryo. These studies led some authors to define cancer as a problem of developmental biology and to predict the present concept of "cancer stem cells theory". In this review, we record the most important researches about the reprogramming and differentiation treatments of cancer cells to better clarify how the substances taken from developing embryo or other biological substances can induce differentiation of malignant cells. Lastly, a model of cancer has been proposed here, conceived by one of us, which is consistent with the reality, as demonstrated by a great number of researches. This model integrates the theory of the "maturation arrest" of cancer cells as conceived by B. Pierce with the theory which describes cancer as a process of deterministic chaos determined by genetic and/or epigenetic alterations in differentiated cells, which leads a normal cell to become cancerous. All the researches here described demonstrated that cancer

  5. Chapter 27 -- Breast Cancer Genomics, Section VI, Pathology and Biological Markers of Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Spellman, Paul T.; Heiser, Laura; Gray, Joe W.

    2009-06-18

    Breast cancer is predominantly a disease of the genome with cancers arising and progressing through accumulation of aberrations that alter the genome - by changing DNA sequence, copy number, and structure in ways that that contribute to diverse aspects of cancer pathophysiology. Classic examples of genomic events that contribute to breast cancer pathophysiology include inherited mutations in BRCA1, BRCA2, TP53, and CHK2 that contribute to the initiation of breast cancer, amplification of ERBB2 (formerly HER2) and mutations of elements of the PI3-kinase pathway that activate aspects of epidermal growth factor receptor (EGFR) signaling and deletion of CDKN2A/B that contributes to cell cycle deregulation and genome instability. It is now apparent that accumulation of these aberrations is a time-dependent process that accelerates with age. Although American women living to an age of 85 have a 1 in 8 chance of developing breast cancer, the incidence of cancer in women younger than 30 years is uncommon. This is consistent with a multistep cancer progression model whereby mutation and selection drive the tumor's development, analogous to traditional Darwinian evolution. In the case of cancer, the driving events are changes in sequence, copy number, and structure of DNA and alterations in chromatin structure or other epigenetic marks. Our understanding of the genetic, genomic, and epigenomic events that influence the development and progression of breast cancer is increasing at a remarkable rate through application of powerful analysis tools that enable genome-wide analysis of DNA sequence and structure, copy number, allelic loss, and epigenomic modification. Application of these techniques to elucidation of the nature and timing of these events is enriching our understanding of mechanisms that increase breast cancer susceptibility, enable tumor initiation and progression to metastatic disease, and determine therapeutic response or resistance. These studies also

  6. Biomimetic tissue-engineered systems for advancing cancer research: NCI Strategic Workshop report.

    Science.gov (United States)

    Schuessler, Teresa K; Chan, Xin Yi; Chen, Huanhuan Joyce; Ji, Kyungmin; Park, Kyung Min; Roshan-Ghias, Alireza; Sethi, Pallavi; Thakur, Archana; Tian, Xi; Villasante, Aranzazu; Zervantonakis, Ioannis K; Moore, Nicole M; Nagahara, Larry A; Kuhn, Nastaran Z

    2014-10-01

    Advanced technologies and biomaterials developed for tissue engineering and regenerative medicine present tractable biomimetic systems with potential applications for cancer research. Recently, the National Cancer Institute convened a Strategic Workshop to explore the use of tissue biomanufacturing for development of dynamic, physiologically relevant in vitro and ex vivo biomimetic systems to study cancer biology and drug efficacy. The workshop provided a forum to identify current progress, research gaps, and necessary steps to advance the field. Opportunities discussed included development of tumor biomimetic systems with an emphasis on reproducibility and validation of new biomimetic tumor models, as described in this report.

  7. Primary energy-transformations in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Lehninger, A.L.

    1980-10-01

    In this paper I shall review the main outlines of current research on the molecular aspects of the primary energy-coupling mechanisms in cells, those carried out by energy-transducing membranes. They include the capture of solar energy by the chloroplast membranes of green plants, used to generate carbohydrates and molecular oxygen from carbon dioxide and water, and the counterpart of photosynthesis, the process of respiration in heterotrophic organisms, in which reduced organic products generated by photosynthesis are oxidized at the expense of dioxygen to form carbon dioxide and water. Although the cycling of dioxygen, carbon dioxide, and organic matter between the plant and animal worlds is well known, it is not generally appreciated that the magnitude of biological energy flux in these cycles is huge compared to the total energy flux in man-made devices. A major consequence is that the concentration of carbon dioxide in the atmosphere has been increasing at a significant rate, at a time when there is also a decrease, at least in some parts of the world, in the counterbalancing utilization of CO/sub 2/ by green plants, due to deforestation. The greenhouse effect of increased atmospheric CO/sub 2/ may not only change the earth's climate, but also may influence the rate of photosynthesis. It is also not generally appreciated that energy flow in the biosphere leads to production of enormous amounts of organic matter potentially useful in furnishing man's energy requirements.

  8. [Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

    Science.gov (United States)

    Maroto Rey, José Pablo; Cillán Narvaez, Elena

    2013-06-01

    There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

  9. Virtual Tissues and Developmental Systems Biology

    Science.gov (United States)

    Computational modeling of embryonic systems to analyze how 'core development processes' are wired together. Has the potential to address environmental and human health factors with broad scientific and economic impacts.

  10. System chemical biology studies of endocrine disruptors

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Oprea, Tudor I.

    Endocrine disrupting chemicals (EDCs) alter hormonal balance and other physiological systems through inappropriate developmental or adult exposure, perturbing the reproductive function of further generations. While disruption of key receptors (e.g., estrogen, androgen, and thyroid) at the ligand...

  11. Effects of Pesticides on Biological Systems

    OpenAIRE

    Ergul Belge Kurutas; Metin Kilinc

    2003-01-01

    The use of pesticid both in Turkey and other contries is widespread in order to combat against many pests which cause economical damages. However, pesticides in human pass through skin, respiratory or digestive systems and is metabolized by monooxygenase system dependent upon cytocrome P450 in liver. They also give rise to severe decreases cytochrome P450 and amount of "hem" enzyme activites of glucose-6-phosphatase, pyrophosphatase by stimulating lipid peroxidation on hepatic microsomes. In ...

  12. Computational Modeling, Formal Analysis, and Tools for Systems Biology.

    Directory of Open Access Journals (Sweden)

    Ezio Bartocci

    2016-01-01

    Full Text Available As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science.

  13. Application of Bioinformatics and Systems Biology in Medicinal Plant Studies

    Institute of Scientific and Technical Information of China (English)

    DENG You-ping; AI Jun-mei; XIAO Pei-gen

    2010-01-01

    One important purpose to investigate medicinal plants is to understand genes and enzymes that govern the biological metabolic process to produce bioactive compounds.Genome wide high throughput technologies such as genomics,transcriptomics,proteomics and metabolomics can help reach that goal.Such technologies can produce a vast amount of data which desperately need bioinformatics and systems biology to process,manage,distribute and understand these data.By dealing with the"omics"data,bioinformatics and systems biology can also help improve the quality of traditional medicinal materials,develop new approaches for the classification and authentication of medicinal plants,identify new active compounds,and cultivate medicinal plant species that tolerate harsh environmental conditions.In this review,the application of bioinformatics and systems biology in medicinal plants is briefly introduced.

  14. Computational Modeling, Formal Analysis, and Tools for Systems Biology.

    Science.gov (United States)

    Bartocci, Ezio; Lió, Pietro

    2016-01-01

    As the amount of biological data in the public domain grows, so does the range of modeling and analysis techniques employed in systems biology. In recent years, a number of theoretical computer science developments have enabled modeling methodology to keep pace. The growing interest in systems biology in executable models and their analysis has necessitated the borrowing of terms and methods from computer science, such as formal analysis, model checking, static analysis, and runtime verification. Here, we discuss the most important and exciting computational methods and tools currently available to systems biologists. We believe that a deeper understanding of the concepts and theory highlighted in this review will produce better software practice, improved investigation of complex biological processes, and even new ideas and better feedback into computer science.

  15. Complex Biological Systems Analysis of Cell Cycling Models in Carcinogenesis: I. The essential roles of modifications in the c-Myc, TP53/p53, p27 and hTERT modules in Cancer Initiation and Progression

    CERN Document Server

    Prisecaru, V I

    2004-01-01

    A new approach to the integration of results from a modular, complex biological systems analysis of nonlinear dynamics in cell cycling network transformations that are leading to carcinogenesis is proposed. Carcinogenesis is a complex process that involves dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments that form numerous inter-related pathways referred to as networks. One such network module contains the cell cyclins whose functions are essential to cell cycling and division. Cyclins are proteins that also link to several critical pro-apoptotic and other cell cycling/division components, such as: c-Myc, p27, the tumor suppressor gene TP53 and its product-- the p53 protein with key roles in controlling DNA repair, inducing apoptosis and activating p21 (which can depress cell cyclins if activated), mdm2(with its biosynthesis activated by p53 and also, in its turn, inhibiting p53), p21, the Thomsen-Friedenreich antigen(T- antigen),Rb,Bax, Ba...

  16. Towards Engineering Biological Systems in a Broader Context.

    Science.gov (United States)

    Venturelli, Ophelia S; Egbert, Robert G; Arkin, Adam P

    2016-02-27

    Significant advances have been made in synthetic biology to program information processing capabilities in cells. While these designs can function predictably in controlled laboratory environments, the reliability of these devices in complex, temporally changing environments has not yet been characterized. As human society faces global challenges in agriculture, human health and energy, synthetic biology should develop predictive design principles for biological systems operating in complex environments. Natural biological systems have evolved mechanisms to overcome innumerable and diverse environmental challenges. Evolutionary design rules should be extracted and adapted to engineer stable and predictable ecological function. We highlight examples of natural biological responses spanning the cellular, population and microbial community levels that show promise in synthetic biology contexts. We argue that synthetic circuits embedded in host organisms or designed ecologies informed by suitable measurement of biotic and abiotic environmental parameters could be used as engineering substrates to achieve target functions in complex environments. Successful implementation of these methods will broaden the context in which synthetic biological systems can be applied to solve important problems.

  17. PathSys: integrating molecular interaction graphs for systems biology

    Directory of Open Access Journals (Sweden)

    Raval Alpan

    2006-02-01

    Full Text Available Abstract Background The goal of information integration in systems biology is to combine information from a number of databases and data sets, which are obtained from both high and low throughput experiments, under one data management scheme such that the cumulative information provides greater biological insight than is possible with individual information sources considered separately. Results Here we present PathSys, a graph-based system for creating a combined database of networks of interaction for generating integrated view of biological mechanisms. We used PathSys to integrate over 14 curated and publicly contributed data sources for the budding yeast (S. cerevisiae and Gene Ontology. A number of exploratory questions were formulated as a combination of relational and graph-based queries to the integrated database. Thus, PathSys is a general-purpose, scalable, graph-data warehouse of biological information, complete with a graph manipulation and a query language, a storage mechanism and a generic data-importing mechanism through schema-mapping. Conclusion Results from several test studies demonstrate the effectiveness of the approach in retrieving biologically interesting relations between genes and proteins, the networks connecting them, and of the utility of PathSys as a scalable graph-based warehouse for interaction-network integration and a hypothesis generator system. The PathSys's client software, named BiologicalNetworks, developed for navigation and analyses of molecular networks, is available as a Java Web Start application at http://brak.sdsc.edu/pub/BiologicalNetworks.

  18. Towards Engineering Biological Systems in a Broader Context.

    Science.gov (United States)

    Venturelli, Ophelia S; Egbert, Robert G; Arkin, Adam P

    2016-02-27

    Significant advances have been made in synthetic biology to program information processing capabilities in cells. While these designs can function predictably in controlled laboratory environments, the reliability of these devices in complex, temporally changing environments has not yet been characterized. As human society faces global challenges in agriculture, human health and energy, synthetic biology should develop predictive design principles for biological systems operating in complex environments. Natural biological systems have evolved mechanisms to overcome innumerable and diverse environmental challenges. Evolutionary design rules should be extracted and adapted to engineer stable and predictable ecological function. We highlight examples of natural biological responses spanning the cellular, population and microbial community levels that show promise in synthetic biology contexts. We argue that synthetic circuits embedded in host organisms or designed ecologies informed by suitable measurement of biotic and abiotic environmental parameters could be used as engineering substrates to achieve target functions in complex environments. Successful implementation of these methods will broaden the context in which synthetic biological systems can be applied to solve important problems. PMID:26546279

  19. Contributions of stochastic events to biological evolution and cancer

    Directory of Open Access Journals (Sweden)

    Anderson KM

    2015-10-01

    Full Text Available Stochastic genetic and epigenetic events have been fundamental in contributing to the development of manifold life-forms, past and present. The development of malignant cell clones and the role of stochasticity as a driving force in cancer cell evolution complements, in a perverse way evidence for the role of chance in normal cellular development and evolution. Stochastic events at multiple levels of cellular control and implementation represent a primary driving force and an ultimate filter through which evolutionary innovation occurs. Stochasticity provides the opportunity for a random assortment of disparate genetic and epigenetic events, in some instances resulting in altered metabolic and developmental capabilities of sufficient stability and uniqueness to contribute to deterministic sequelae that promote the viability and procreation of cells under stress. Cellular evolution has so far resulted in a “survival of a (sic fittest”, often dependent mechanistically on and determined by stochastic events. The implications of this are mirrored in the evolution of malignant change, to some extent as a variant of “reverse engineering” of dedifferentiation. Efforts to reduce the incidence of malignant change will have to take in to account its random nature and further the understanding of this feature.

  20. Biologically-Inspired Water Propulsion System

    Institute of Scientific and Technical Information of China (English)

    Andrzej Sioma

    2013-01-01

    Most propulsion systems of vehicles travelling in the aquatic environment are equipped with propellers.Observations of nature,however,show that the absolute majority of organisms travel through water using wave motion,paddling or using water jet power.Inspired by these observations of nature,an innovative propulsion system working in aquatic environment was developed.This paper presents the design of the water propulsion system.Particular attention was paid to the use of paddling techniques and water jet power.A group of organisms that use those mechanisms to travel through water was selected and analysed.The results of research were used in the design of a propulsion system modelled simultaneously on two methods of movement in the aquatic environment.A method for modelling a propulsion system using a combination of the two solutions and the result were described.A conceptual design and a prototype constructed based on the solution were presented.With respect to the solution developed,studies and analyses of selected parameters of the prototype were described.

  1. Computational Proteomics: High-throughput Analysis for Systems Biology

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, William R.; Webb-Robertson, Bobbie-Jo M.

    2007-01-03

    High-throughput (HTP) proteomics is a rapidly developing field that offers the global profiling of proteins from a biological system. The HTP technological advances are fueling a revolution in biology, enabling analyses at the scales of entire systems (e.g., whole cells, tumors, or environmental communities). However, simply identifying the proteins in a cell is insufficient for understanding the underlying complexity and operating mechanisms of the overall system. Systems level investigations are relying more and more on computational analyses, especially in the field of proteomics generating large-scale global data.

  2. Construction of a Linux based chemical and biological information system.

    Science.gov (United States)

    Molnár, László; Vágó, István; Fehér, András

    2003-01-01

    A chemical and biological information system with a Web-based easy-to-use interface and corresponding databases has been developed. The constructed system incorporates all chemical, numerical and textual data related to the chemical compounds, including numerical biological screen results. Users can search the database by traditional textual/numerical and/or substructure or similarity queries through the web interface. To build our chemical database management system, we utilized existing IT components such as ORACLE or Tripos SYBYL for database management and Zope application server for the web interface. We chose Linux as the main platform, however, almost every component can be used under various operating systems.

  3. Influence of TACE combined with radioactive seed radiotherapy on primary liver cancer patients’ malignant biological indicators

    Institute of Scientific and Technical Information of China (English)

    Yao Liu; Yu Wang; Guang-Yan Lei; Xiao-Hong Yan; Qiao Yang; Hai-Ping Zhu; Yi Geng

    2016-01-01

    Objective:To analyze the influence of TACE combined with radioactive seed radiotherapy on primary liver cancer patients’ malignant biological indicators.Methods:A total of 112 cases of primary liver cancer patients who received treatment in our hospital, Xijing Hospital and Tumor Hospital of Shaanxi Province were chosen as research subjects and divided into control group (TACE therapy alone) with 63 cases in it and observation group (TACE combined with radioactive seed radiotherapy) with 49 cases according to different treatment, and then the levels of malignant biological indicators after 2 months of treatment were compared between two groups.Results:Serum VEGF, FGF and MMP levels of observation group after treatment were significantly lower than those of control group; serum AFP-L3, GP73, Sb7-H3, AFU and CatS levels were significantly lower than those of control group; serum ICAM-1, ESM-1 and uPA levels were lower than those of control group.Conclusion: TACE combined with radioactive seed radiotherapy can effectively reduce primary liver cancer patients’ serum malignant biological indicator levels, decrease the degree of malignancy of cancer cells and slow disease progression, and is an ideal treatment.

  4. nab-Paclitaxel in combination with biologically targeted agents for early and metastatic breast cancer.

    Science.gov (United States)

    Megerdichian, Christine; Olimpiadi, Yuliya; Hurvitz, Sara A

    2014-06-01

    Taxanes are highly active chemotherapeutic agents used in the treatment of early-stage and metastatic breast cancer. Novel formulations have been developed to improve efficacy and decrease toxicity associated with these cytotoxic agents. nab-Paclitaxel is a biologically interactive, solvent-free, 130-nm-sized albumin-bound paclitaxel, developed to avoid the Cremophor vehicle used in solvent-based paclitaxel. Based on a pivotal phase 3 study, nab-paclitaxel was shown to be safely infused at a significantly higher dose of paclitaxel than the doses used with standard paclitaxel therapy, and had a shorter infusion time, no premedication, and higher response rates. It is now approved in the United States for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant therapy, and has demonstrated promising efficacy and favorable tolerability. Recently, several phase 2 and 3 studies have suggested a role for nab-paclitaxel in combination with biologically targeted agents for the treatment of early- and late-stage breast cancer. This review will discuss the findings of clinical trials evaluating nab-paclitaxel in combination with biologically targeted therapeutic agents for breast cancer in the neoadjuvant, adjuvant, and metastatic settings. PMID:24560997

  5. Biologic Therapy in Inflammatory Immunomediated Systemic Diseases: Safety Profile.

    Science.gov (United States)

    Moroncini, Gianluca; Albani, Lisa; Nobili, Lorenzo; Gabrielli, Armando

    2016-01-01

    The discovery of some key molecular mechanisms underlying the dysregulation of the immune system responsible for inflammatory systemic diseases as severe as Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), and Systemic Vasculitides, led to the development and subsequent introduction into clinical practice of biological drugs which are significantly improving the management of such complex disorders. This novel molecular targeted therapeutics represents in fact a valid alternative or complementary treatment to conventional immunosuppressive strategies, characterized by broad, unspecific actions and severe adverse effects. Main advantages of the use of biologic drugs reside in their steroid-sparing effect and in the ability of inducing remission of refractory disease states or curing specific organ involvements. Aim of this article is to review and briefly discuss the scientific evidence supporting the use of biologics in these diseases, with a particular emphasis on their efficacy and safety profile compared to the canonical drugs.

  6. Circadian systems biology: When time matters

    Directory of Open Access Journals (Sweden)

    Luise Fuhr

    2015-01-01

    In this manuscript we review the combination of experimental methodologies, bioinformatics and theoretical models that have been essential to explore this remarkable timing-system. Such an integrative and interdisciplinary approach may provide new strategies with regard to chronotherapeutic treatment and new insights concerning the restoration of the circadian timing in clock-associated diseases.

  7. Metagenomic Systems Biology of the Human Microbiome

    DEFF Research Database (Denmark)

    Bonde, Ida

    in the system. Applying the CAG clustering method to data from the human gut microbiome, we identified dependency-associations between plasmids, phages and clone-specific gene sets to their bacterial host. Connections between CRISPR-elements and phages were also observed. Additionally, the persistence of some...

  8. [Adhesive cell interactions in the biology of cancer].

    Science.gov (United States)

    Bocharova, O A

    2002-01-01

    The present review describes a hypothesis for a critical role of cell adhesive interactions in tumorigenesis. Dysregulation of tissue cell-cell interactions initiates first of all local (in the tissue) and then general (in whole body) conditions for tumor growth. Otherwise imbalance of tissue-specific adhesion factor at the very beginning of carcinogenesis is considered to trigger a cascade of pathological reactions responsible for more severe adhesive disorders that are in turn critical for the "totalitarian" behavior of a tumor and its "colonization" of other tissues and organs. Impaired disturbance is likely to be the key mechanism of carcinogenesis since it is significantly associated with the main features of a tumor: tissue proliferation control loss, anaplasia, invasion, metastasis, and immune surveillance deficit. The hypothesis is supported by evolutionary, biological, histological, immunological, and clinical arguments whose combination does not characterize any other known mechanisms of oncogenesis. The concept of adhesiveness opens new possibilities for the diagnosis, prevention, and treatment of tumors and also improves a strategy for designing new drugs.

  9. Dendritic cell vaccines in cancer immunotherapy: from biology to translational medicine

    Institute of Scientific and Technical Information of China (English)

    Hongmei Xu; Xuetao Cao

    2011-01-01

    According to the GLOBOCAN reports,there were about 12.7 million cancer cases and 7.6 million cancer deaths in 2008,and the cancer burden continues to increase worldwide [1].At present,the common treatments for cancer include surgery,chemotherapy,radiotherapy,and immunotherapy.Immunotherapy aims to enhance or regulate the patient's own immune response to fight against tumors.It represents a novel and effective strategy in cancer treatments,but,generally,its efficacy needs to be improved [2].Cancer vaccination is an important and promising approach in cancer immunotherapy.For many years,prophylactic vaccines have exhibited profound accomplishment in preventing serious infectious diseases in humankind,including polio,small pox,and diphtheria.However,cancer vaccines are vastly different from the prophylactic vaccines in that they are aimed to eliminate preexisting tumors.Furthermore,the immune system is immunosuppressed in most cancer patients,so it is much more difficult to develop effective cancer vaccines.

  10. Using the Unified Modelling Language (UML) to guide the systemic description of biological processes and systems.

    Science.gov (United States)

    Roux-Rouquié, Magali; Caritey, Nicolas; Gaubert, Laurent; Rosenthal-Sabroux, Camille

    2004-07-01

    One of the main issues in Systems Biology is to deal with semantic data integration. Previously, we examined the requirements for a reference conceptual model to guide semantic integration based on the systemic principles. In the present paper, we examine the usefulness of the Unified Modelling Language (UML) to describe and specify biological systems and processes. This makes unambiguous representations of biological systems, which would be suitable for translation into mathematical and computational formalisms, enabling analysis, simulation and prediction of these systems behaviours.

  11. 59. Cold Spring Harbor symposium on quantitative biology: Molecular genetics of cancer

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-12-31

    Investigation of the mechanistic aspects of cancer has its roots in the studies on tumor viruses and their effects on cell proliferation, function, and growth. This outstanding progress was well documented in previous Cold Spring Harbor Symposia on Quantitative Biology. In the early to mid 1980s, progress on the development of chromosome mapping strategies and the accumulation of DNA probes that identified polymorphisms, encouraged by the international Human Genome Project, enabled the identification of other genes that contributed to familial inheritance of high susceptibility to specific cancers. This approach was very successful and led to a degree of optimism that one aspect of cancer, the multistep genetic process from early neoplasia to metastatic tumors, was beginning to be understood. It therefore seemed appropriate that the 59th Symposium on Quantitative Biology focus attention on the Molecular Genetics of Cancer. The concept was to combine the exciting progress on the identification of new genetic alterations in human tumor cells with studies on the function of the cancer gene products and how they go awry in tumor cells.

  12. Stochastic Physics, Complex Systems and Biology

    OpenAIRE

    Qian, Hong

    2012-01-01

    In complex systems, the interplay between nonlinear and stochastic dynamics, e.g., J. Monod's necessity and chance, gives rise to an evolutionary process in Darwinian sense, in terms of discrete jumps among attractors, with punctuated equilibrium, spontaneous random "mutations" and "adaptations". On an evlutionary time scale it produces sustainable diversity among individuals in a homogeneous population rather than convergence as usually predicted by a deterministic dynamics. The emergent dis...

  13. Systems Biology of the Vervet Monkey

    OpenAIRE

    Jasinska, Anna J.; Schmitt, Christopher A.; Susan K Service; Cantor, Rita M.; Dewar, Ken; James D. Jentsch; Kaplan, Jay R; Turner, Trudy R.; Warren, Wesley C.; George M Weinstock; Woods, Roger P.; Freimer, Nelson B.

    2013-01-01

    Nonhuman primates (NHP) provide crucial biomedical model systems intermediate between rodents and humans. The vervet monkey (also called the African green monkey) is a widely used NHP model that has unique value for genetic and genomic investigations of traits relevant to human diseases. This article describes the phylogeny and population history of the vervet monkey and summarizes the use of both captive and wild vervet monkeys in biomedical research. It also discusses the effort of an inter...

  14. Integrative systems biology approaches in asthma pharmacogenomics

    OpenAIRE

    Dahlin, Amber; Tantisira, Kelan G.

    2012-01-01

    In order to improve therapeutic outcomes, there is a tremendous need to identify patients who are likely to respond to a given asthma treatment. Pharmacogenomic studies have explained a portion of the variability in drug response and provided an increasing list of candidate genes and SNPs. However, as phenotypic variation arises from a network of complex interactions among genetic and environmental factors, rather than individual genes or SNPs, a multidisciplinary, systems-level approach is r...

  15. Characteristic responses of biological and nanoscale systems in the terahertz frequency range

    Energy Technology Data Exchange (ETDEWEB)

    Angeluts, A A; Balakin, A V; Evdokimov, M G; Ozheredov, I A; Sapozhnikov, D A; Solyankin, P M; Shkurinov, A P [International Laser Center, M. V. Lomonosov Moscow State University, Moscow (Russian Federation); Esaulkov, M N; Nazarov, M M [Institute on Laser and Information Technologies, Russian Academy of Sciences, Shatura, Moscow Region (Russian Federation); Cherkasova, O P [Institute of Laser Physics, Siberian Branch, Russian Academy of Sciences, Novosibirsk (Russian Federation)

    2014-07-31

    This paper briefly examines methods for the generation of pulsed terahertz radiation and principles of pulsed terahertz spectroscopy, an advanced informative method for studies of complex biological and nanostructured systems. Some of its practical applications are described. Using a number of steroid hormones as examples, we demonstrate that terahertz spectroscopy in combination with molecular dynamics methods and computer simulation allows one to gain information about the structure of molecules in crystals. A 'terahertz colour vision' method is proposed for analysis of pulsed terahertz signals reflected from biological tissues and it is shown that this method can be effectively used to analyse the properties of biological tissues and for early skin cancer diagnosis. (laser biophotonics)

  16. Systems Biology Brings Life Sciences Closer--Report on the China-UK Systems Biology Workshop 2005

    Institute of Scientific and Technical Information of China (English)

    Ming Chen

    2005-01-01

    @@ The China-UK Systems Biology Workshop 2005 was held during June 20-21 in the National Science Park of Zhejiang University, Hangzhou, China. It was organized by the Institute of Bioinformatics, Zhejiang University, and was initiated by Prof. Dr. Jun Zhu (Zhejiang University) and Prof. Dr. John Findlay (University of Leeds, UK). The workshop was part of the program called UK-China Partners in Science, a one-year campaign that was initiated by the British government to explore more collaborations between UK and China on science and technology. It was attended also by a representative of this program, Mr.Frank Yuan, senior science & innovation officer. The idea of the workshop was to bring together experts with specialists in systems biology in order to promote the "natural partnership" between scientists from the two countries. The most important items of systems biology considered at the workshop were: (1) New technologies and advances in systems biology; (2) Research developments in genomics and proteomics; (3) New methodologies and software in computational biology; (4) Research collaboration on systems biology between China and UK.

  17. Improving Collaboration by Standardization Efforts in Systems Biology

    OpenAIRE

    Dräger, Andreas; Palsson, Bernhard Ø.

    2014-01-01

    Collaborative genome-scale reconstruction endeavors of metabolic networks would not be possible without a common, standardized formal representation of these systems. The ability to precisely define biological building blocks together with their dynamic behavior has even been considered a prerequisite for upcoming synthetic biology approaches. Driven by the requirements of such ambitious research goals, standardization itself has become an active field of research on nearly all levels of gran...

  18. Enterobacter aerogenes Needle Stick Leads to Improved Biological Management System

    Energy Technology Data Exchange (ETDEWEB)

    Johanson, Richard E.

    2004-08-01

    A laboratory worker who received a needle stick from a contaminated needle while working with a culture containing Enterobactor aerogenes developed a laboratory acquired infection. Although this organism has been shown to cause community and nosocomial infections, there have been no documented cases of a laboratory acquired infections. Lessons learned from the event led to corrective actions which included modification of lab procedures, development of a biological inventory tracking and risk identification system and the establishment of an effective biological safety program.

  19. Learning (from) the errors of a systems biology model

    OpenAIRE

    Benjamin Engelhardt; Holger Frőhlich; Maik Kschischo

    2016-01-01

    Mathematical modelling is a labour intensive process involving several iterations of testing on real data and manual model modifications. In biology, the domain knowledge guiding model development is in many cases itself incomplete and uncertain. A major problem in this context is that biological systems are open. Missed or unknown external influences as well as erroneous interactions in the model could thus lead to severely misleading results. Here we introduce the dynamic elastic-net, a dat...

  20. Systems-biology dissection of eukaryotic cell growth

    Directory of Open Access Journals (Sweden)

    Andrews Justen

    2010-05-01

    Full Text Available Abstract A recent article in BMC Biology illustrates the use of a systems-biology approach to integrate data across the transcriptome, proteome and metabolome of budding yeast in order to dissect the relationship between nutrient conditions and cell growth. See research article http://jbiol.com/content/6/2/4 and http://www.biomedcentral.com/1741-7007/8/68

  1. Application of computational systems biology to explore environmental toxicity hazards

    DEFF Research Database (Denmark)

    Audouze, Karine Marie Laure; Grandjean, Philippe

    2011-01-01

    ) to ascertain their possible links to relevant adverse effects.Methods: We extracted chemical-protein association networks for each DDT isomer and its metabolites using ChemProt, a disease chemical biology database that includes both binding and gene expression data, and we explored protein-protein interactions...... diseases were linked to the two DDT isomers. Asthma was uniquely linked with p,p´-DDT, and autism with o,p´-DDT. Several reproductive and neurobehavioral outcomes and cancer types were linked to all three compounds.Conclusions: Computer-based modeling relies on available information. Although differences...

  2. Phase transitions in fluids and biological systems

    Science.gov (United States)

    Sipos, Maksim

    In this thesis, I consider systems from two seemingly different fields: fluid dynamics and microbial ecology. In these systems, the unifying features are the existences of global non-equilibrium steady states. I consider generic and statistical models for transitions between these global states, and I relate the model results with experimental data. A theme of this thesis is that these rather simple, minimal models are able to capture a lot of functional detail about complex dynamical systems. In Part I, I consider the transition between laminar and turbulent flow. I find that quantitative and qualitative features of pipe flow experiments, the superexponential lifetime and the splitting of turbulent puffs, and the growth rate of turbulent slugs, can all be explained by a coarse-grained, phenomenological model in the directed percolation universality class. To relate this critical phenomena approach closer to the fluid dynamics, I consider the transition to turbulence in the Burgers equation, a simplified model for Navier-Stokes equations. Via a transformation to a model of directed polymers in a random medium, I find that the transition to Burgers turbulence may also be in the directed percolation universality class. This evidence implies that the turbulent-to-laminar transition is statistical in nature and does not depend on details of the Navier-Stokes equations describing the fluid flow. In Part II, I consider the disparate subject of microbial ecology where the complex interactions within microbial ecosystems produce observable patterns in microbe abundance, diversity and genotype. In order to be able to study these patterns, I develop a bioinformatics pipeline to multiply align and quickly cluster large microbial metagenomics datasets. I also develop a novel metric that quantifies the degree of interactions underlying the assembly of a microbial ecosystem, particularly the transition between neutral (random) and niche (deterministic) assembly. I apply this

  3. Decoherence and Spin Echo in Biological Systems

    CERN Document Server

    Nesterov, Alexander I

    2015-01-01

    The spin echo approach is extended to include bio-complexes for which the interaction with dynamical noise is strong. Significant restoration of the free induction decay signal due to homogeneous (decoherence) and inhomogeneous (dephasing) broadening is demonstrated analytically and numerically, for both an individual dimer of interacting chlorophylls and for an ensemble of dimers. This approach is based on an exact and closed system of ordinary differential equations that can be easily solved for a wide range of parameters that are relevant for bio-applications.

  4. Stress, catecholaminergic system and cancer.

    Science.gov (United States)

    Krizanova, O; Babula, P; Pacak, K

    2016-07-01

    Stress as a modern civilization factor significantly affects our lives. While acute stress might have a positive effect on the organism, chronic stress is usually detrimental and might lead to serious health complications. It is known that stress induced by the physical environment (temperature-induced cold stress) can significantly impair the efficacy of cytotoxic chemotherapies and the anti-tumor immune response. On the other hand, epidemiological evidence has shown that patients taking drugs known as β-adrenergic antagonists ("β-blockers"), which are commonly prescribed to treat arrhythmia, hypertension, and anxiety, have significantly lower rates of several cancers. In this review, we summarize the current knowledge about catecholamines as important stress hormones in tumorigenesis and discuss the use of β-blockers as the potential therapeutic agents.

  5. Biological systems: from water radiolysis to carbon ion radiotherapy

    Science.gov (United States)

    Beuve, Michael; Moreau, Jean-Michel; Rodriguez, Claire; Testa, Etienne

    2015-07-01

    Hadron therapy is an innovative cancer treatment method based on the acceleration of light ions at high energy. In addition to their interesting profile of dose deposition, which ensures accurate targeting of localized tumors, carbon ions offer biological properties that lead to an efficient treatment for radio- and chemo-resistant tumors and to provide a boost for tumors in hypoxia. This paper is a short review of the progress in theoretical, experimental, fundamental and applied research, aiming at understanding the origin of the biological benefits of light ions better. As a limit of such a vast and multidisciplinary domain, this review adopts the point of view of the physicists, leaning on results obtained in connection with CIMAP's IRRABAT platform.

  6. Modeling of Biological Intelligence for SCM System Optimization

    Directory of Open Access Journals (Sweden)

    Shengyong Chen

    2012-01-01

    Full Text Available This article summarizes some methods from biological intelligence for modeling and optimization of supply chain management (SCM systems, including genetic algorithms, evolutionary programming, differential evolution, swarm intelligence, artificial immune, and other biological intelligence related methods. An SCM system is adaptive, dynamic, open self-organizing, which is maintained by flows of information, materials, goods, funds, and energy. Traditional methods for modeling and optimizing complex SCM systems require huge amounts of computing resources, and biological intelligence-based solutions can often provide valuable alternatives for efficiently solving problems. The paper summarizes the recent related methods for the design and optimization of SCM systems, which covers the most widely used genetic algorithms and other evolutionary algorithms.

  7. Biologically Inspired Execution Framework for Vulnerable Workflow Systems

    CERN Document Server

    Safdar, Sohail; Qureshi, Muhammad Aasim; Akbar, Rehan

    2009-01-01

    The main objective of the research is to introduce a biologically inspired execution framework for workflow systems under threat due to some intrusion attack. Usually vulnerable systems need to be stop and put into wait state, hence to insure the data security and privacy while being recovered. This research ensures the availability of services and data to the end user by keeping the data security, privacy and integrity intact. To achieve the specified goals, the behavior of chameleons and concept of hibernation has been considered in combination. Hence the workflow systems become more robust using biologically inspired methods and remain available to the business consumers safely even in a vulnerable state.

  8. Using Entropy Leads to a Better Understanding of Biological Systems

    Directory of Open Access Journals (Sweden)

    Chih-Yuan Tseng

    2010-12-01

    Full Text Available In studying biological systems, conventional approaches based on the laws of physics almost always require introducing appropriate approximations. We argue that a comprehensive approach that integrates the laws of physics and principles of inference provides a better conceptual framework than these approaches to reveal emergence in such systems. The crux of this comprehensive approach hinges on entropy. Entropy is not merely a physical quantity. It is also a reasoning tool to process information with the least bias. By reviewing three distinctive examples from protein folding dynamics to drug design, we demonstrate the developments and applications of this comprehensive approach in the area of biological systems.

  9. [Biological implant in single-stage reconstruction of mammary gland for cancer].

    Science.gov (United States)

    Zikiriakhodzhaev, A D; Ermoshchenkova, M V

    2015-01-01

    Brief literature review about features of biological implants application for mammary gland reconstruction is presented in the article. Possible complications after such materials use, first experience of acellular dermal matrix administration for single-stage mammary gland reconstruction in 6 patients with breast cancer are also described. We offered surgical techniques, complications and methods of its treatment. We presented advantages of biological implant use which are consisted in decrease of surgical damage and duration of surgery, opportunity for enlargement of pocket for implant, decrease of pain syndrome. PMID:25909549

  10. Interactive analysis of systems biology molecular expression data

    Directory of Open Access Journals (Sweden)

    Prabhakar Sunil

    2008-02-01

    Full Text Available Abstract Background Systems biology aims to understand biological systems on a comprehensive scale, such that the components that make up the whole are connected to one another and work through dependent interactions. Molecular correlations and comparative studies of molecular expression are crucial to establishing interdependent connections in systems biology. The existing software packages provide limited data mining capability. The user must first generate visualization data with a preferred data mining algorithm and then upload the resulting data into the visualization package for graphic visualization of molecular relations. Results Presented is a novel interactive visual data mining application, SysNet that provides an interactive environment for the analysis of high data volume molecular expression information of most any type from biological systems. It integrates interactive graphic visualization and statistical data mining into a single package. SysNet interactively presents intermolecular correlation information with circular and heatmap layouts. It is also applicable to comparative analysis of molecular expression data, such as time course data. Conclusion The SysNet program has been utilized to analyze elemental profile changes in response to an increasing concentration of iron (Fe in growth media (an ionomics dataset. This study case demonstrates that the SysNet software is an effective platform for interactive analysis of molecular expression information in systems biology.

  11. Gap junctional intercellular communication as a biological "Rosetta stone" in understanding, in a systems biological manner, stem cell behavior, mechanisms of epigenetic toxicology, chemoprevention and chemotherapy.

    Science.gov (United States)

    Trosko, James E

    2007-08-01

    In spite of the early speculation by Loewenstein that one of the critical distinguishing phenotypes of cancers from normal cells was the dysfunction of gap junctional intercellular communication (GJIC), this hypothesis has not captured the attention of most birth defects and cancer researchers. Moreover, even with later demonstrations that factors that influence normal development and carcinogenesis by modulating GJIC, such as chemical teratogens and tumor-promoting chemicals, inflammatory factors, hormones and growth factors, antisense connexin genes, knockout mouse models, human inherited mutated connexin genes, si-connexin RNA, chemopreventive and chemotherapeutic chemicals, it is rare that one sees any reference to these studies by the mainstream investigators in these fields. Based on the assumption that the evolutionarily conserved connexin genes found in metazoans are needed for normal development and the maintenance of health and T. Dobzhansky's statement "Nothing in biology makes sense except in the light of evolution," a short review of the roles of endogenous and exogenous modulators of GJIC will be made in the context of the multistage, multimechanism process of carcinogenesis, the stem cell theory of carcinogenesis, the discovery and characterization of normal adult stem "cancer stem" cells and the observation that two distinct classes of GJIC-deficient cancer cells are known. The implications of these observations to a "systems biological" view of the role of gap junctions and the nutritional prevention and treatment of several chronic diseases and cancer will be discussed.

  12. What's behind the Biological Classification System in Use Today?

    Science.gov (United States)

    Robertson, William C.

    2010-01-01

    Whether students should memorize classification schemes (taxonomies) is a column in itself, but the author can address the role that this system plays in the study of biology. To that end, it will help to address how the system developed over time. And toward "that" end, you will do a simple activity to start. (Contains 3 figures.)

  13. Structural Systems Biology Evaluation of Metabolic Thermotolerance in Escherichia coli

    DEFF Research Database (Denmark)

    Chang, Roger L.; Andrews, Kathleen; Kim, Donghyuk;

    2013-01-01

    Improve the System A "systems biology" approach may clarify, for example, how particular proteins determine sensitivity of bacteria to extremes of temperature. Chang et al. (p. 1220) integrated information on protein structure with a model of metabolism, thus associating the protein structure of ...

  14. Chemical imaging of biological systems with the scanning electrochemical microscope.

    Science.gov (United States)

    Gyurcsányi, Róbert E; Jágerszki, Gyula; Kiss, Gergely; Tóth, Klára

    2004-06-01

    A brief overview on recent advances in the application of scanning electrochemical microscopy (SECM) to the investigation of biological systems is presented. Special emphasis is given to the mapping of local enzyme activity by SECM, which is exemplified by relevant original systems. PMID:15110274

  15. 3D Modelling of Biological Systems for Biomimetics

    Institute of Scientific and Technical Information of China (English)

    Shujun Zhang; Kevin Hapeshi; Ashok K. Bhattacharya

    2004-01-01

    With the advanced development of computer-based enabling technologies, many engineering, medical, biology,chemistry, physics and food science etc have developed to the unprecedented levels, which lead to many research and development interests in various multi-discipline areas. Among them, biomimetics is one of the most promising and attractive branches of study. Biomimetics is a branch of study that uses biological systems as a model to develop synthetic systems.To learn from nature, one of the fundamental issues is to understand the natural systems such animals, insects, plants and human beings etc. The geometrical characterization and representation of natural systems is an important fundamental work for biomimetics research. 3D modeling plays a key role in the geometrical characterization and representation, especially in computer graphical visualization. This paper firstly presents the typical procedure of 3D modelling methods and then reviews the previous work of 3D geometrical modelling techniques and systems developed for industrial, medical and animation applications. Especially the paper discusses the problems associated with the existing techniques and systems when they are applied to 3D modelling of biological systems. Based upon the discussions, the paper proposes some areas of research interests in 3D modelling of biological systems and for Biomimetics.

  16. The Use of an Electronic Response System in Teaching Biology

    Science.gov (United States)

    Bessler, William C.; Nisbet, Jerry J.

    1971-01-01

    An electronic student response system was used in teaching college biology to non-science students. Achievement of this treatment group was compared with that of the control group (not utilizing the response system). The only statistical significant difference found in an analysis of covariance was an interaction between treatment group and time…

  17. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems

    DEFF Research Database (Denmark)

    Mardare, Radu Iulian; Ihekwaba, Adoha

    2007-01-01

    A. Ihekwaba, R. Mardare. A Calculus for Modelling, Simulating and Analysing Compartmentalized Biological Systems. Case study: NFkB system. In Proc. of International Conference of Computational Methods in Sciences and Engineering (ICCMSE), American Institute of Physics, AIP Proceedings, N 2...

  18. Biological Water Dynamics and Entropy: A Biophysical Origin of Cancer and Other Diseases

    Directory of Open Access Journals (Sweden)

    Stephanie Seneff

    2013-09-01

    Full Text Available This paper postulates that water structure is altered by biomolecules as well as by disease-enabling entities such as certain solvated ions, and in turn water dynamics and structure affect the function of biomolecular interactions. Although the structural and dynamical alterations are subtle, they perturb a well-balanced system sufficiently to facilitate disease. We propose that the disruption of water dynamics between and within cells underlies many disease conditions. We survey recent advances in magnetobiology, nanobiology, and colloid and interface science that point compellingly to the crucial role played by the unique physical properties of quantum coherent nanomolecular clusters of magnetized water in enabling life at the cellular level by solving the “problems” of thermal diffusion, intracellular crowding, and molecular self-assembly. Interphase water and cellular surface tension, normally maintained by biological sulfates at membrane surfaces, are compromised by exogenous interfacial water stressors such as cationic aluminum, with consequences that include greater local water hydrophobicity, increased water tension, and interphase stretching. The ultimate result is greater “stiffness” in the extracellular matrix and either the “soft” cancerous state or the “soft” neurodegenerative state within cells. Our hypothesis provides a basis for understanding why so many idiopathic diseases of today are highly stereotyped and pluricausal.

  19. Systems Biology: The Role of Engineering in the Reverse Engineering of Biological Signaling

    OpenAIRE

    Iglesias, Pablo A.

    2013-01-01

    One of the principle tasks of systems biology has been the reverse engineering of signaling networks. Because of the striking similarities to engineering systems, a number of analysis and design tools from engineering disciplines have been used in this process. This review looks at several examples including the analysis of homeostasis using control theory, the attenuation of noise using signal processing, statistical inference and the use of information theory to understand both binary decis...

  20. A Systems Biology Approach in Therapeutic Response Study for Different Dosing Regimens—a Modeling Study of Drug Effects on Tumor Growth using Hybrid Systems

    OpenAIRE

    Xiangfang Li; Lijun Qian; Bittner, Michale L.; Dougherty, Edward R.

    2012-01-01

    Motivated by the frustration of translation of research advances in the molecular and cellular biology of cancer into treatment, this study calls for cross-disciplinary efforts and proposes a methodology of incorporating drug pharmacology information into drug therapeutic response modeling using a computational systems biology approach. The objectives are two fold. The first one is to involve effective mathematical modeling in the drug development stage to incorporate preclinical and clinical...

  1. Computational approaches to metabolic engineering utilizing systems biology and synthetic biology.

    Science.gov (United States)

    Fong, Stephen S

    2014-08-01

    Metabolic engineering modifies cellular function to address various biochemical applications. Underlying metabolic engineering efforts are a host of tools and knowledge that are integrated to enable successful outcomes. Concurrent development of computational and experimental tools has enabled different approaches to metabolic engineering. One approach is to leverage knowledge and computational tools to prospectively predict designs to achieve the desired outcome. An alternative approach is to utilize combinatorial experimental tools to empirically explore the range of cellular function and to screen for desired traits. This mini-review focuses on computational systems biology and synthetic biology tools that can be used in combination for prospective in silico strain design.

  2. Hepatocellular carcinoma: a systems biology perspective

    Directory of Open Access Journals (Sweden)

    Lorenza Alice D'alessandro

    2013-02-01

    Full Text Available Hepatocellular carcinomas (HCC have different etiology and heterogenic genomic alterations lead to high complexity. The molecular features of HCC have largely been studied by gene expression and proteome profiling focusing on the correlations between the expression of specific markers and clinical data. Integration of the increasing amounts of data in databases has facilitated the link of genomic and proteomic profiles of HCC to disease state and clinical outcome. Despite the current knowledge, specific molecular markers remain to be identified and new strategies are required to establish novel targeted therapies. In the last years, mathematical models reconstructing gene and protein networks based on experimental data of HCC have been developed providing powerful tools to predict candidate interactions and potential targets for therapy. Furthermore, the combination of dynamic and logical mathematical models with quantitative data allows detailed mechanistic insights into system properties. To address effects at the organ level, mathematical models reconstructing the three-dimensional organization of liver lobules were developed. In the future, integration of different modeling approaches capturing the effects at the cellular up to the organ level is required to address the complex properties of HCC and to enable the discovery of new targets for HCC prevention or treatment.

  3. Expression genomics in breast cancer research: microarrays at the crossroads of biology and medicine

    OpenAIRE

    Miller, Lance D; Liu, Edison T

    2007-01-01

    Genome-wide expression microarray studies have revealed that the biological and clinical heterogeneity of breast cancer can be partly explained by information embedded within a complex but ordered transcriptional architecture. Comprising this architecture are gene expression networks, or signatures, reflecting biochemical and behavioral properties of tumors that might be harnessed to improve disease subtyping, patient prognosis and prediction of therapeutic response. Emerging 'hypothesis-driv...

  4. Multiscale approach predictions for biological outcomes in ion-beam cancer therapy

    OpenAIRE

    Alexey Verkhovtsev; Eugene Surdutovich; Solov’yov, Andrey V.

    2016-01-01

    Ion-beam therapy provides advances in cancer treatment, offering the possibility of excellent dose localization and thus maximising cell-killing within the tumour. The full potential of such therapy can only be realised if the fundamental mechanisms leading to lethal cell damage under ion irradiation are well understood. The key question is whether it is possible to quantitatively predict macroscopic biological effects caused by ion radiation on the basis of physical and chemical effects rela...

  5. Instant Abdominal Wall Reconstruction with Biologic Mesh following Resection of Locally Advanced Colonic Cancer

    OpenAIRE

    Oskay Kaya; Engin Olcucuoglu; Gaye Seker; Hakan Kulacoglu

    2012-01-01

    We present a case of immediate abdominal wall reconstruction with biologic mesh following the resection of locally advanced colonic cancer. The tumor in the right colon did not respond to neoadjuvant chemotherapy. Surgical enbloc excision, including excision of the invasion in the abdominal wall, was achieved, and the defect was reconstructed with porcine dermal collagen mesh. The patient was discharged with no complication, and adaptation of the mesh was excellent at the six-month followup.

  6. Intraductal Proliferative Lesions of the Breast—Terminology and Biology Matter: Premalignant Lesions or Preinvasive Cancer?

    OpenAIRE

    Maria Mauri; Lucio Fortunato; Leopoldo Costarelli; Domenico Campagna

    2012-01-01

    Morphological criteria for the diagnosis of intraductal proliferative lesions of the breast have been an object of research and much controversy, and its terminology is rather confusing. Knowledge of the molecular aspects of this disease probably necessitates further research to clarify if these entities can be identified as breast cancer precursors or as a malignant preinvasive disease. These issues are of great interest not only for their biological implications, but also to the clinician w...

  7. Systems Biology Approaches to a Rational Drug Discovery Paradigm.

    Science.gov (United States)

    Prathipati, Philip; Mizuguchi, Kenji

    2016-01-01

    Ligand- and structure-based drug design approaches complement phenotypic and target screens, respectively, and are the two major frameworks for guiding early-stage drug discovery efforts. Since the beginning of this century, the advent of the genomic era has presented researchers with a myriad of high throughput biological data (parts lists and their interaction networks) to address efficacy and toxicity, augmenting the traditional ligand- and structure-based approaches. This data rich era has also presented us with challenges related to integrating and analyzing these multi-platform and multi-dimensional datasets and translating them into viable hypotheses. Hence in the present paper, we review these existing approaches to drug discovery research and argue the case for a new systems biology based approach. We present the basic principles and the foundational arguments/underlying assumptions of the systems biology based approaches to drug design. Also discussed are systems biology data types (key entities, their attributes and their relationships with each other, and data models/representations), software and tools used for both retrospective and prospective analysis, and the hypotheses that can be inferred. In addition, we summarize some of the existing resources for a systems biology based drug discovery paradigm (open TG-GATEs, DrugMatrix, CMap and LINCs) in terms of their strengths and limitations. PMID:26306988

  8. Systems Biology Approaches to a Rational Drug Discovery Paradigm.

    Science.gov (United States)

    Prathipati, Philip; Mizuguchi, Kenji

    2016-01-01

    Ligand- and structure-based drug design approaches complement phenotypic and target screens, respectively, and are the two major frameworks for guiding early-stage drug discovery efforts. Since the beginning of this century, the advent of the genomic era has presented researchers with a myriad of high throughput biological data (parts lists and their interaction networks) to address efficacy and toxicity, augmenting the traditional ligand- and structure-based approaches. This data rich era has also presented us with challenges related to integrating and analyzing these multi-platform and multi-dimensional datasets and translating them into viable hypotheses. Hence in the present paper, we review these existing approaches to drug discovery research and argue the case for a new systems biology based approach. We present the basic principles and the foundational arguments/underlying assumptions of the systems biology based approaches to drug design. Also discussed are systems biology data types (key entities, their attributes and their relationships with each other, and data models/representations), software and tools used for both retrospective and prospective analysis, and the hypotheses that can be inferred. In addition, we summarize some of the existing resources for a systems biology based drug discovery paradigm (open TG-GATEs, DrugMatrix, CMap and LINCs) in terms of their strengths and limitations.

  9. Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Nielsen, Jens; Jewett, Michael Christopher

    2008-01-01

    Saccharomyces cerevisiae is extremely well suited for this objective. As one of the most intensely studied eukaryotic model organisms, a rich density of knowledge detailing its genetics, biochemistry, physiology, and large-scale fermentation performance can be capitalized upon to enable a substantial increase...... in the industrial application of this yeast. Developments in genomics and high-throughput systems biology tools are enhancing one's ability to rapidly characterize cellular behaviour, which is valuable in the field of metabolic engineering where strain characterization is often the bottleneck in strain development...... programmes. Here, the impact of systems biology on metabolic engineering is reviewed and perspectives on the role of systems biology in the design of cell factories are given....

  10. Learning (from) the errors of a systems biology model

    Science.gov (United States)

    Engelhardt, Benjamin; Frőhlich, Holger; Kschischo, Maik

    2016-02-01

    Mathematical modelling is a labour intensive process involving several iterations of testing on real data and manual model modifications. In biology, the domain knowledge guiding model development is in many cases itself incomplete and uncertain. A major problem in this context is that biological systems are open. Missed or unknown external influences as well as erroneous interactions in the model could thus lead to severely misleading results. Here we introduce the dynamic elastic-net, a data driven mathematical method which automatically detects such model errors in ordinary differential equation (ODE) models. We demonstrate for real and simulated data, how the dynamic elastic-net approach can be used to automatically (i) reconstruct the error signal, (ii) identify the target variables of model error, and (iii) reconstruct the true system state even for incomplete or preliminary models. Our work provides a systematic computational method facilitating modelling of open biological systems under uncertain knowledge.

  11. Continuum analysis of biological systems conserved quantities, fluxes and forces

    CERN Document Server

    Suraishkumar, G K

    2014-01-01

    This book addresses the analysis, in the continuum regime, of biological systems at various scales, from the cellular level to the industrial one. It presents both fundamental conservation principles (mass, charge, momentum and energy) and relevant fluxes resulting from appropriate driving forces, which are important for the analysis, design and operation of biological systems. It includes the concept of charge conservation, an important principle for biological systems that is not explicitly covered in any other book of this kind. The book is organized in five parts: mass conservation; charge conservation; momentum conservation; energy conservation; and multiple conservations simultaneously applied. All mathematical aspects are presented step by step, allowing any reader with a basic mathematical background (calculus, differential equations, linear algebra, etc.) to follow the text with ease. The book promotes an intuitive understanding of all the relevant principles and in so doing facilitates their applica...

  12. Biologically erodable microspheres as potential oral drug delivery systems

    Science.gov (United States)

    Mathiowitz, Edith; Jacob, Jules S.; Jong, Yong S.; Carino, Gerardo P.; Chickering, Donald E.; Chaturvedi, Pravin; Santos, Camilla A.; Vijayaraghavan, Kavita; Montgomery, Sean; Bassett, Michael; Morrell, Craig

    1997-03-01

    Biologically adhesive delivery systems offer important advantages1-5 over conventional drug delivery systems6. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium for extended periods of time and actually penetrate it, through and between cells. Thus, once loaded with compounds of pharmacological interest, the microspheres could be developed as delivery systems to transfer biologically active molecules to the circulation. We show that these microspheres increase the absorption of three model substances of widely different molecular size: dicumarol, insulin and plasmid DNA.

  13. Modulation of radiosensitivity of biological systems by medicinal herbs

    International Nuclear Information System (INIS)

    The global environmental pollution is responsible for the exposure of living beings to the influence of various technogenic factors, including ionizing radiation. Exposure to such radiation represents a genuine, increasing threat to mankind and our environment. The steadily increasing applications of radiation in clinical practice, industrial and agricultural activities, residual radio-activity resulting from nuclear test explosions, have a measurable impact contributing to significant radiation hazards in humans. Further, the proliferation of terrorism and asymmetric warfare in the 21st century has rendered the modern world a dangerous place to live and work. With the realization of deleterious effects of ionizing radiation, a need was felt to protect human beings against these harmful effects by using physical and/or chemical means. Many chemical compounds have been tested for radio protective action but their practical applicability remained limited owing to their inherent toxicity at the optimum dose level. Various plants have been used for various ailments in humans since time immemorial, and herbal preparations have usually been considered safe and less toxic than the synthetic compounds. Therefore, screening of natural products present a major avenue for the discovery of new radio protective drugs and such products have drawn the attention of investigators during the last two decades. The Indian system of medicine employs a large number of plants and some of these herbals viz. The extracts of certain medicinal plant like Amla (Emblica officinalis), Rosemary (Rosemary officinalis), Methi (Trigonella foenum graecum) sapthaparna (Alstonia scholaris), Bael (Aegle inarmelos), Bhumi amla (Phyllanthus niruri), Jamun (Syzgium cumini), Gloe (Tinospora cordifolia) have been trialed in this laboratory for their radio protective action in various biological systems of mammals. The extracts of various parts of such plants have appreciable DRF on the basis of survival

  14. Molecular subtype analysis determines the association of advanced breast cancer in Egypt with favorable biology

    Directory of Open Access Journals (Sweden)

    DuQuette Rachelle A

    2011-09-01

    Full Text Available Abstract Background Prognostic markers and molecular breast cancer subtypes reflect underlying biological tumor behavior and are important for patient management. Compared to Western countries, women in North Africa are less likely to be prognosticated and treated based on well-characterized markers such as the estrogen receptor (ER, progesterone receptor (PR and Her2. We conducted this study to determine the prevalence of breast cancer molecular subtypes in the North African country of Egypt as a measure of underlying biological characteristics driving tumor manifestations. Methods To determine molecular subtypes we characterized over 200 tumor specimens obtained from Egypt by performing ER, PR, Her2, CK5/6, EGFR and Ki67 immunohistochemistry. Results Our study demonstrated that the Luminal A subtype, associated with favorable prognosis, was found in nearly 45% of cases examined. However, the basal-like subtype, associated with poor prognosis, was found in 11% of cases. These findings are in sharp contrast to other parts of Africa in which the basal-like subtype is over-represented. Conclusions Egyptians appear to have favorable underlying biology, albeit having advanced disease at diagnosis. These data suggest that Egyptians would largely profit from early detection of their disease. Intervention at the public health level, including education on the benefits of early detection is necessary and would likely have tremendous impact on breast cancer outcome in Egypt.

  15. Cancer-Specific Telomerase Reverse Transcriptase (TERT Promoter Mutations: Biological and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Tiantian Liu

    2016-07-01

    Full Text Available The accumulated evidence has pointed to a key role of telomerase in carcinogenesis. As a RNA-dependent DNA polymerase, telomerase synthesizes telomeric DNA at the end of linear chromosomes, and attenuates or prevents telomere erosion associated with cell divisions. By lengthening telomeres, telomerase extends cellular life-span or even induces immortalization. Consistent with its functional activity, telomerase is silent in most human normal somatic cells while active only in germ-line, stem and other highly proliferative cells. In contrast, telomerase activation widely occurs in human cancer and the enzymatic activity is detectable in up to 90% of malignancies. Recently, hotspot point mutations in the regulatory region of the telomerase reverse transcriptase (TERT gene, encoding the core catalytic component of telomerase, was identified as a novel mechanism to activate telomerase in cancer. This review discusses the cancer-specific TERT promoter mutations and potential biological and clinical significances.

  16. Cancer-Specific Telomerase Reverse Transcriptase (TERT) Promoter Mutations: Biological and Clinical Implications

    Science.gov (United States)

    Liu, Tiantian; Yuan, Xiaotian; Xu, Dawei

    2016-01-01

    The accumulated evidence has pointed to a key role of telomerase in carcinogenesis. As a RNA-dependent DNA polymerase, telomerase synthesizes telomeric DNA at the end of linear chromosomes, and attenuates or prevents telomere erosion associated with cell divisions. By lengthening telomeres, telomerase extends cellular life-span or even induces immortalization. Consistent with its functional activity, telomerase is silent in most human normal somatic cells while active only in germ-line, stem and other highly proliferative cells. In contrast, telomerase activation widely occurs in human cancer and the enzymatic activity is detectable in up to 90% of malignancies. Recently, hotspot point mutations in the regulatory region of the telomerase reverse transcriptase (TERT) gene, encoding the core catalytic component of telomerase, was identified as a novel mechanism to activate telomerase in cancer. This review discusses the cancer-specific TERT promoter mutations and potential biological and clinical significances. PMID:27438857

  17. Cancer-Specific Telomerase Reverse Transcriptase (TERT) Promoter Mutations: Biological and Clinical Implications.

    Science.gov (United States)

    Liu, Tiantian; Yuan, Xiaotian; Xu, Dawei

    2016-01-01

    The accumulated evidence has pointed to a key role of telomerase in carcinogenesis. As a RNA-dependent DNA polymerase, telomerase synthesizes telomeric DNA at the end of linear chromosomes, and attenuates or prevents telomere erosion associated with cell divisions. By lengthening telomeres, telomerase extends cellular life-span or even induces immortalization. Consistent with its functional activity, telomerase is silent in most human normal somatic cells while active only in germ-line, stem and other highly proliferative cells. In contrast, telomerase activation widely occurs in human cancer and the enzymatic activity is detectable in up to 90% of malignancies. Recently, hotspot point mutations in the regulatory region of the telomerase reverse transcriptase (TERT) gene, encoding the core catalytic component of telomerase, was identified as a novel mechanism to activate telomerase in cancer. This review discusses the cancer-specific TERT promoter mutations and potential biological and clinical significances. PMID:27438857

  18. Biology and potential clinical implications of tissue inhibitor of metalloproteinases-1 in colorectal cancer treatment

    DEFF Research Database (Denmark)

    Sørensen, Nanna Møller; Sørensen, irene Vejgaard; Würtz, Sidse Ørnbjerg;

    2008-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the industrialized world. About half of "curatively" resected patients develop recurrent disease within the next 3-5 years despite the lack of clinical, histological and biochemical evidence of remaining overt disease...... after resection of the primary tumour. Availability of validated biological markers for early detection, selection for adjuvant therapy, prediction of treatment efficacy and monitoring of treatment efficacy would most probably increase survival. Tissue inhibitor of metalloproteinases-1 (TIMP-1) may...... patients, suggesting that TIMP-1 could have a tumour-promoting function. Furthermore, measurement of plasma TIMP-1 has been shown to be useful for disease detection, with a high sensitivity and high specificity for early-stage colon cancer. This review describes some basic information on the current...

  19. [Experimental models in oncology: contribution of cell culture on understanding the biology of cancer].

    Science.gov (United States)

    Cruz, Mariana; Enes, Margarida; Pereira, Marta; Dourado, Marília; Sarmento Ribeiro, Ana Bela

    2009-01-01

    In the beginning of the 20th century, tissue culture was started with the aim of studying the behaviour of animal cells in normal and stress conditions. The cell study at molecular level depends on their capacity of growing and how they can be manipulated in laboratory. In vitro cell culture allows us the possibility of studying biological key processes, such as growth, differentiation and cell death, and also to do genetic manipulations essential to the knowledge of structure and genes function. Human stem cells culture provides strategies to circumvent other models' deficiencies. It seems that cancer stem cells remain quiescent until activation by appropriated micro-environmental stimulation. Several studies reveal that different cancer types could be due to stem cell malignant transformations. Removal of these cells is essential to the development of more effective cancer therapies for advanced disease. On the other hand, dendritic cells modified in culture may be used as a therapeutic vaccine in order to induce tumour withdraw.

  20. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

    Directory of Open Access Journals (Sweden)

    Pascoe Abigail C

    2012-03-01

    Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

  1. The epidermal growth factor receptors as biological targets in penile cancer.

    Science.gov (United States)

    Di Lorenzo, Giuseppe; Buonerba, Carlo; Ferro, Matteo; Calderoni, Giuseppe; Bozza, Giovanni; Federico, Piera; Tedesco, Beatrice; Ruggieri, Vitalba; Aieta, Michele

    2015-04-01

    Penile cancer is a rare disease, with an incidence that is higher in less developed countries and is in the range of 1 - 10 per 100000 men worldwide. Early diagnosis is essential for cure, as 5 year cancer-specific survival is 90 - 100 % in patients with intraepithelial neoplasms and in those with low-grade superficial tumors without lymphovascular invasion, but it drops to 30% in men with multiple mobile or bilateral inguinal lymph nodes. The EGFR family plays a major role in penile cancer biology, with distinct receptors being involved in HPV-positive and -negative tumors. A number of anti-EGFR agents were used in penile cancer patients outside the context of a clinical trial, mainly as a salvage treatment after failure of first-line chemotherapy. A total of 28 patients received anti-EGFR monoclonal antibodies, with 50% of them showing a response to treatment, and a median PFS of ∼ 3 months. The rarity of the disease poses great challenge in terms of education and awareness of the general population, planning of preventive measures on a large scale, as well as conduction of prospective trials and approval of high-cost biological therapy. PMID:25496291

  2. Detection methods predict differences in biology and survival in breast cancer patients

    International Nuclear Information System (INIS)

    The aim of this study was to measure the biological characteristics involved in tumorigenesis and the progression of breast cancer in symptomatic and screen-detected carcinomas to identify possible differences. For this purpose, we evaluated clinical-pathological parameters and proliferative and apoptotic activities in a series of 130 symptomatic and 161 screen-detected tumors. After adjustment for the smaller size of the screen-detected carcinomas compared with symptomatic cancers, those detected in the screening program presented longer disease-free survival (RR = 0.43, CI = 0.19-0.96) and had high estrogen and progesterone receptor concentrations more often than did symptomatic cancers (OR = 3.38, CI = 1.72-6.63 and OR = 3.44, CI = 1.94-6.10, respectively). Furthermore, the expression of bcl-2, a marker of good prognosis in breast cancer, was higher and HER2/neu expression was lower in screen-detected cancers than in symptomatic cancers (OR = 1.77, CI = 1.01-3.23 and OR = 0.64, CI = 0.40-0.98, respectively). However, when comparing prevalent vs incident screen-detected carcinomas, prevalent tumors were larger (OR = 2.84, CI = 1.05-7.69), were less likely to be HER2/neu positive (OR = 0.22, CI = 0.08-0.61) and presented lower Ki67 expression (OR = 0.36, CI = 0.17-0.77). In addition, incident tumors presented a shorter survival time than did prevalent ones (RR = 4.88, CI = 1.12-21.19). Incident carcinomas include a variety of screen-detected carcinomas that exhibit differences in biology and prognosis relative to prevalent carcinomas. The detection method is important and should be taken into account when making therapy decisions

  3. Investigation of bacterial populations in a biological nutrient removal system

    OpenAIRE

    Kavanaugh, Rathi G.

    1991-01-01

    Bacterial populations proliferating in a pilot scale biological nutrient removal system (BNR) were studied. The objective of the research was to develop media and methods to identify bacterial populations in BNR systems. Samples were obtained from the last aerobic zone of a University of Cape Town (UCT)-type system. The most probable numbers (MPN) of bacteria in the samples were analyzed in liquid media containing volatile fatty acids as sole sources of carbon. Samples...

  4. The Systems Biology Research Tool: evolvable open-source software

    OpenAIRE

    Wright Jeremiah; Wagner Andreas

    2008-01-01

    Abstract Background Research in the field of systems biology requires software for a variety of purposes. Software must be used to store, retrieve, analyze, and sometimes even to collect the data obtained from system-level (often high-throughput) experiments. Software must also be used to implement mathematical models and algorithms required for simulation and theoretical predictions on the system-level. Results We introduce a free, easy-to-use, open-source, integrated software platform calle...

  5. Normal and impaired charge transport in biological systems

    Energy Technology Data Exchange (ETDEWEB)

    Miller, John H., E-mail: jhmiller@uh.edu [Department of Physics & Texas Center for Superconductivity, University of Houston, Houston, TX 77204-5005 (United States); Villagrán, Martha Y. Suárez; Maric, Sladjana [Department of Physics & Texas Center for Superconductivity, University of Houston, Houston, TX 77204-5005 (United States); Briggs, James M. [Department of Biology & Biochemistry, University of Houston, Houston, TX 77204-5001 (United States)

    2015-03-01

    We examine the physics behind some of the causes (e.g., hole migration and localization that cause incorrect base pairing in DNA) and effects (due to amino acid replacements affecting mitochondrial charge transport) of disease-implicated point mutations, with emphasis on mutations affecting mitochondrial DNA (mtDNA). First we discuss hole transport and localization in DNA, including some of our quantum mechanical modeling results, as they relate to certain mutations in cancer. Next, we give an overview of electron and proton transport in the mitochondrial electron transport chain, and how such transport can become impaired by mutations implicated in neurodegenerative diseases, cancer, and other major illnesses. In particular, we report on our molecular dynamics (MD) studies of a leucine→arginine amino acid replacement in ATP synthase, encoded by the T→G point mutation at locus 8993 of mtDNA. This mutation causes Leigh syndrome, a devastating maternally inherited neuromuscular disorder, and has been found to trigger rapid tumor growth in prostate cancer cell lines. Our MD results suggest, for the first time, that this mutation adversely affects water channels that transport protons to and from the c-ring of the rotary motor ATP synthase, thus impairing the ability of the motor to produce ATP. Finally, we discuss possible future research topics for biological physics, such as mitochondrial complex I, a large proton-pumping machine whose physics remains poorly understood.

  6. Controlled biological and biomimetic systems for landmine detection.

    Science.gov (United States)

    Habib, Maki K

    2007-08-30

    Humanitarian demining requires to accurately detect, locate and deactivate every single landmine and other buried mine-like objects as safely and as quickly as possible, and in the most non-invasive manner. The quality of landmine detection affects directly the efficiency and safety of this process. Most of the available methods to detect explosives and landmines are limited by their sensitivity and/or operational complexities. All landmines leak with time small amounts of their explosives that can be found on surrounding ground and plant life. Hence, explosive signatures represent the robust primary indicator of landmines. Accordingly, developing innovative technologies and efficient techniques to identify in real-time explosives residue in mined areas represents an attractive and promising approach. Biological and biologically inspired detection technology has the potential to compete with or be used in conjunction with other artificial technology to complement performance strengths. Biological systems are sensitive to many different scents concurrently, a property that has proven difficult to replicate artificially. Understanding biological systems presents unique opportunities for developing new capabilities through direct use of trained bio-systems, integration of living and non-living components, or inspiring new design by mimicking biological capabilities. It is expected that controlled bio-systems, biotechnology and microbial techniques will contribute to the advancement of mine detection and other application domains. This paper provides directions, evaluation and analysis on the progress of controlled biological and biomimetic systems for landmine detection. It introduces and discusses different approaches developed, underlining their relative advantages and limitations, and highlighting trends, safety and ecology concern, and possible future directions. PMID:17662594

  7. Reconstruction of the pelvic floor with a biological mesh after abdominoperineal excision for rectal cancer

    DEFF Research Database (Denmark)

    Wille-Jørgensen, Peer; Pilsgaard, B.; Moller, P.

    2009-01-01

    The aim of the study is to describe the results of reconstruction of the pelvic floor by using an absorbable biological mesh after having performed an abdomino-perineal resection with excision of whole of the pelvic floor for rectal cancer Eleven consecutive patients had reconstruction...... of the pelvic floor after abdominoperineal excision (APR) with a biological mesh. The peri- and postoperative courses were registered in a prospective database. Six patients received preoperative radiochemotherapy. One patient had the mesh removed due to infection and later developed local recurrence. The rest...... had an uneventful postoperative course despite more pain than is usually experienced in the perineal wound after traditional APR. The use of a biological mesh for pelvic floor reconstruction is feasible with satisfactory results. A randomised trial is warranted in order to evaluate this technique...

  8.  Biological therapies in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Dorota Suszek

    2012-08-01

    Full Text Available  The prevention of chronic organic damage and complete inhibition of inflammatory activity of the disease are the main goals in the treatment of systemic lupus erythematosus (SLE. Current therapies of SLE are not effective enough and they may cause various serious side effects. Biological therapies, affecting important pathogenetic disturbances in the immunological system of SLE patients, give hope for the development of a new treatment for SLE. Currently the most advanced clinical trials are being conducted with anti-lymphocyte B drugs, such as rituximab, belimumab and epratuzumab. Belimumab as the first biological agent was registered for treatment of the active, seropositive form of SLE. The advances in immunology and rheumatology nowadays raise the hope of finding effective and safe treatment for SLE. In our article we present an overview of data concerning perspectives of biological treatment in SLE.

  9. Evolutionary tradeoffs between economy and effectiveness in biological homeostasis systems.

    Directory of Open Access Journals (Sweden)

    Pablo Szekely

    Full Text Available Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical. For example, regulatory systems that are designed to repair damage must be effective in reducing damage, but economical in not making too many repair proteins because making excessive proteins carries a fitness cost to the cell, called protein burden. In order to see how biological systems compromise between the two tasks of effectiveness and economy, we applied an approach from economics and engineering called Pareto optimality. This approach allows calculating the best-compromise systems that optimally combine the two tasks. We used a simple and general model for regulation, known as integral feedback, and showed that best-compromise systems have particular combinations of biochemical parameters that control the response rate and basal level. We find that the optimal systems fall on a curve in parameter space. Due to this feature, even if one is able to measure only a small fraction of the system's parameters, one can infer the rest. We applied this approach to estimate parameters in three biological systems: response to heat shock and response to DNA damage in bacteria, and calcium homeostasis in mammals.

  10. Understanding Cancer Prognosis

    Medline Plus

    Full Text Available ... Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer Leukemia Lung ... Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & Early Detection Treatment Cancer & Public Health Cancer Health ...

  11. Texosome-based drug delivery system for cancer therapy:from past to present

    Institute of Scientific and Technical Information of China (English)

    Hamideh Mahmoodzadeh Hosseini; Raheleh Halabian; Mohsen Amin; Abbas Ali Imani Fooladi

    2015-01-01

    Rising worldwide cancer incidence and resistance to current anti-cancer drugs necessitate the need for new pharmaceutical compounds and drug delivery system. Malfunction of the immune system, particularly in the tumor microenvironment, causes tumor growth and enhances tumor progression. Thus, cancer immunotherapy can be an appropriate approach to provoke the systemic immune system to combat tumor expansion. Texosomes, which are endogenous nanovesicles released by all tumor cells, contribute to cell-cell communication and modify the phenotypic features of recipient cells due to the texosomes’ ability to transport biological components. For this reason, texosome-based delivery system can be a valuable strategy for therapeutic purposes. To improve the pharmaceutical behavior of this system and to facilitate its use in medical applications, biotechnology approaches and mimetic techniques have been utilized. In this review, we present the development history of texosome-based delivery systems and discuss the advantages and disadvantages of each system.

  12. Synthetic biology approaches in cancer immunotherapy, genetic network engineering, and genome editing.

    Science.gov (United States)

    Chakravarti, Deboki; Cho, Jang Hwan; Weinberg, Benjamin H; Wong, Nicole M; Wong, Wilson W

    2016-04-18

    Investigations into cells and their contents have provided evolving insight into the emergence of complex biological behaviors. Capitalizing on this knowledge, synthetic biology seeks to manipulate the cellular machinery towards novel purposes, extending discoveries from basic science to new applications. While these developments have demonstrated the potential of building with biological parts, the complexity of cells can pose numerous challenges. In this review, we will highlight the broad and vital role that the synthetic biology approach has played in applying fundamental biological discoveries in receptors, genetic circuits, and genome-editing systems towards translation in the fields of immunotherapy, biosensors, disease models and gene therapy. These examples are evidence of the strength of synthetic approaches, while also illustrating considerations that must be addressed when developing systems around living cells.

  13. No biological evidence of XMRV in blood or prostatic fluid from prostate cancer patients.

    Directory of Open Access Journals (Sweden)

    Ramon Mendoza

    Full Text Available BACKGROUND: XMRV (xenotropic murine leukemia virus-related virus was initially discovered in association with prostate cancer and later with chronic fatigue syndrome (CFS. Its association with CFS is now largely discredited, and current results support a laboratory origin for XMRV with no reproducible evidence for infection of humans. However, some results indicating the presence of XMRV in prostate cancer are difficult to attribute to sample contamination. Here we have sought biological evidence that might confirm the presence of XMRV in prostate cancer samples previously having tested positive. METHODS AND RESULTS: We have tested for infectious XMRV and neutralizing antibodies against XMRV in blood plasma from 29 subjects with prostate cancer, and for infectious XMRV in prostate secretions from another five prostate cancer subjects. Nine of these subjects had previously tested positive for XMRV by PCR or by virus assay. We did not detect XMRV or related retroviruses in any sample, and the neutralizing activities of the plasma samples were all very low, a result inconsistent with XMRV infection of the plasma donors. CONCLUSIONS: We find no evidence for XMRV infection of any human subject tested, either by assay for infectious virus or for neutralizing antibodies. Our results are consistent with the majority of published studies on XMRV, which find that XMRV is not present in humans. The observed low to undetectable XMRV neutralization by human plasma indicates a lack of innate restriction of XMRV replication by soluble factors in human blood.

  14. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm

    Energy Technology Data Exchange (ETDEWEB)

    Vargas, Hebert Alberto; Sala, Evis; Hricak, Hedvig [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Grimm, Jan [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Program in Molecular Pharmacology and Chemistry, Memorial Sloan Kettering Cancer Center, New York (United States); Donati, Olivio F. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland)

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. (orig.)

  15. INTERNATIONAL CONFERENCE ON INTELLIGENT SYSTEMS FOR MOLECULAR BIOLOGY (ISMB)

    Energy Technology Data Exchange (ETDEWEB)

    Debra Goldberg; Matthew Hibbs; Lukas Kall; Ravikumar Komandurglayavilli; Shaun Mahony; Voichita Marinescu; Itay Mayrose; Vladimir Minin; Yossef Neeman; Guy Nimrod; Marian Novotny; Stephen Opiyo; Elon Portugaly; Tali Sadka; Noboru Sakabe; Indra Sarkar; Marc Schaub; Paul Shafer; Olena Shmygelska; Gregory Singer; Yun Song; Bhattacharya Soumyaroop; Michael Stadler; Pooja Strope; Rong Su; Yuval Tabach; Hongseok Tae; Todd Taylor; Michael Terribilini; Asha Thomas; Nam Tran; Tsai-Tien Tseng; Akshay Vashist; Parthiban Vijaya; Kai Wang; Ting Wang; Lai Wei; Yong Woo; Chunlei Wu; Yoshihiro Yamanishi; Changhui Yan; Jack Yang; Mary Yang; Ping Ye; Miao Zhang

    2009-12-29

    The Intelligent Systems for Molecular Biology (ISMB) conference has provided a general forum for disseminating the latest developments in bioinformatics on an annual basis for the past 13 years. ISMB is a multidisciplinary conference that brings together scientists from computer science, molecular biology, mathematics and statistics. The goal of the ISMB meeting is to bring together biologists and computational scientists in a focus on actual biological problems, i.e., not simply theoretical calculations. The combined focus on “intelligent systems” and actual biological data makes ISMB a unique and highly important meeting, and 13 years of experience in holding the conference has resulted in a consistently well organized, well attended, and highly respected annual conference. The ISMB 2005 meeting was held June 25-29, 2005 at the Renaissance Center in Detroit, Michigan. The meeting attracted over 1,730 attendees. The science presented was exceptional, and in the course of the five-day meeting, 56 scientific papers, 710 posters, 47 Oral Abstracts, 76 Software demonstrations, and 14 tutorials were presented. The attendees represented a broad spectrum of backgrounds with 7% from commercial companies, over 28% qualifying for student registration, and 41 countries were represented at the conference, emphasizing its important international aspect. The ISMB conference is especially important because the cultures of computer science and biology are so disparate. ISMB, as a full-scale technical conference with refereed proceedings that have been indexed by both MEDLINE and Current Contents since 1996, bridges this cultural gap.

  16. Request for Travel Funds for Systems Radiation Biology Workshop

    Energy Technology Data Exchange (ETDEWEB)

    Barcellos-Hoff, Mary Helen [NYU School of Medicine

    2014-03-22

    The 3rd International Systems Radiation Biology Workshop brought together the major European, US and Japanese research programs on radiation risk as well as selected experts representing systems biological approaches to discuss how the new methodologies could be best exploited for low dose research. A significant part of the workshop was devoted to discussions organised as breakout group sessions. To facilitate discussions number of participants was limited to 60 persons. To achieve the goals of this symposium in this international conference, support from DOE is vital. Hence, this proposal requested support in the amount of $15,000 to cover the travel expenses of international experts and radiation biology scientists from the United States. This supporting mechanism was clearly identified to the selected US participants as a conference support award from the DOE (See attached PDF). The workshop was an outstanding opportunity to strengthen interactions between leading experts in the emerging areas of radiation sciences, and will also provide opportunities for younger scientists to meet with experts and discuss their results. This workshop was designed to endorse active engagement in international collaboration. A major objective of this conference was to effectively communicate research results, in order to ensure that current thinking reflects sound science of radiation biology. Further, this international event addressed the use and success of scientific initiatives in radiation biology for policymakers, standard-setters, and the general public.

  17. A systematic literature review on reviews and meta-analyses of biologically based CAM-practices for cancer patients

    DEFF Research Database (Denmark)

    Paludan-Müller, Christine; Lunde, Anita; Johannessen, Helle

    2010-01-01

    for the improvement of quality of life. Breast cancer was the most common single type of cancer reviewed (8 reviews), all focused on the relief of side effects, primarily by supplements containing soy/plant hormones. The use of these supplements should be discouraged due to a risk for progression of breast cancer......Purpose To provide an overview and evaluate the evidence of biologically based CAM-practices for cancer patients. Methods Pubmed, Social Science Citation Index, AMED and the Cochrane library were systematically searched for reviews on effects of biologically based CAM-practices, including herbal...... remedies, vitamins and other dietary supplements, for cancer or cancer related symptoms published 2000-2008. All studies were assessed according to the SIGN hierarchy of evidence. Results A total of 78 reviews/meta-analyses were identified. Of these, 32 were evaluated as high-quality, whereas 46 had low...

  18. Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

    OpenAIRE

    He, Fei; Murabito, Ettore; Westerhoff, Hans V

    2016-01-01

    Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased...

  19. System as metaphor in the psychology and biology of shame.

    Science.gov (United States)

    Maunder, R

    1996-01-01

    Biological theories of brain and psychological theories of mind are two systems of explanation that seem related to one another. The nature of the relationship is problematic and constitutes the age-old mind-body problem. The most prominent solutions currently are variations of materialism. While psychological theories can be consistent with materialism, there remains a difficulty in comprehending nonphysical (social, psychological) causes of physical effects. This difficulty is an obstacle to integration in psychiatry, where we routinely assume that illnesses that include or depend on biological dysfunction are caused multifactorially by causal agents such as perceived parental warmth, parental loss, stressful life events, genetics, and personality (Hammen et al. 1992; Kendler et al. 1993). Unity theory adopts the stance that neurobiological theories and psychological theories are essentially disparate explanations of the same psychobiological events; thus the relationship of mind to brain is one of shared reference (Goodman 1991; Maunder 1995). In Goodman's model the gap between biological and psychological systems is not bridgeable. Different conceptual categories refer to the same referents but cannot interact with each other. Stepping into the breach, systems theory has been presented as offering a language that can bridge the gap between psychological and biological theories of causation (Schwartz 1981; Weiner 1989). Thus, there is a controversy about the applicability of systems theory for integration in psychiatry. PMID:8837180

  20. Environmental Noise and Nonlinear Relaxation in Biological Systems

    CERN Document Server

    Spagnolo, B; Spezia, S; Curcio, L; Pizzolato, N; Dubkov, A A; Fiasconaro, A; Adorno, D Persano; Bue, P Lo; Peri, E; Colazza, S

    2011-01-01

    We analyse the effects of environmental noise in three different biological systems: (i) mating behaviour of individuals of \\emph{Nezara viridula} (L.) (Heteroptera Pentatomidae); (ii) polymer translocation in crowded solution; (iii) an ecosystem described by a Verhulst model with a multiplicative L\\'{e}vy noise.

  1. FIELD INVESTIGATION OF BIOLOGICAL TOILET SYSTEMS AND GREY WATER TREATMENT

    Science.gov (United States)

    The objective of the field program was to determine the operational characteristics and overall acceptability of popular models of biological toilets and a few select grey water systems. A field observation scheme was devised to take advantage of in-use sites throughout the State...

  2. System as metaphor in the psychology and biology of shame.

    Science.gov (United States)

    Maunder, R

    1996-01-01

    Biological theories of brain and psychological theories of mind are two systems of explanation that seem related to one another. The nature of the relationship is problematic and constitutes the age-old mind-body problem. The most prominent solutions currently are variations of materialism. While psychological theories can be consistent with materialism, there remains a difficulty in comprehending nonphysical (social, psychological) causes of physical effects. This difficulty is an obstacle to integration in psychiatry, where we routinely assume that illnesses that include or depend on biological dysfunction are caused multifactorially by causal agents such as perceived parental warmth, parental loss, stressful life events, genetics, and personality (Hammen et al. 1992; Kendler et al. 1993). Unity theory adopts the stance that neurobiological theories and psychological theories are essentially disparate explanations of the same psychobiological events; thus the relationship of mind to brain is one of shared reference (Goodman 1991; Maunder 1995). In Goodman's model the gap between biological and psychological systems is not bridgeable. Different conceptual categories refer to the same referents but cannot interact with each other. Stepping into the breach, systems theory has been presented as offering a language that can bridge the gap between psychological and biological theories of causation (Schwartz 1981; Weiner 1989). Thus, there is a controversy about the applicability of systems theory for integration in psychiatry.

  3. Catalytic mechanisms by biological systems : Special issue introduction

    NARCIS (Netherlands)

    Fraaije, Marco W; Scrutton, Nigel S

    2013-01-01

    Research on enzyme mechanisms is advancing knowledge of the chemistry and biochemistry of catalytic mechanisms by biological systems. The structural-dynamical properties of enzymes are of key importance. Advanced methodological approaches and new insights into enzyme functioning, and new emerging ap

  4. Beyond standardization : dynamic software infrastructures for systems biology

    NARCIS (Netherlands)

    Swertz, Morris A.; Jansen, Ritsert C.

    2007-01-01

    Progress in systems biology is seriously hindered by slow production of suitable software infrastructures. Biologists need infrastructure that easily connects to work that is done in other laboratories, for which standardization is helpful. However, the infrastructure must also accommodate the speci

  5. Research Needs for Understanding the Biology of Overdiagnosis in Cancer Screening.

    Science.gov (United States)

    Srivastava, Sudhir; Reid, Brian J; Ghosh, Sharmistha; Kramer, Barnett S

    2016-09-01

    Many cancers offer an extended window of opportunity for early detection and therapeutic intervention that could lead to a reduction in cause-specific mortality. The pursuit of early detection in screening settings has resulted in decreased incidence and mortality for some cancers (e.g., colon and cervical cancers), and increased incidence with only modest or no effect on cause-specific mortality in others (e.g., breast and prostate). Whereas highly sensitive screening technologies are better at detecting a number of suspected "cancers" that are indolent and likely to remain clinically unimportant in the lifetime of a patient, defined as overdiagnosis, they often miss cancers that are aggressive and tend to present clinically between screenings, known as interval cancers. Unrecognized overdiagnosis leads to overtreatment with its attendant (often long-lasting) side effects, anxiety, and substantial financial harm. Existing methods often cannot differentiate indolent lesions from aggressive ones or understand the dynamics of neoplastic progression. To correctly identify the population that would benefit the most from screening and identify the lesions that would benefit most from treatment, the evolving genomic and molecular profiles of individual cancers during the clinical course of progression or indolence must be investigated, while taking into account an individual's genetic susceptibility, clinical and environmental risk factors, and the tumor microenvironment. Practical challenges lie not only in the lack of access to tissue specimens that are appropriate for the study of natural history, but also in the absence of targeted research strategies. This commentary summarizes the recommendations from a diverse group of scientists with expertise in basic biology, translational research, clinical research, statistics, and epidemiology and public health professionals convened to discuss research directions. J. Cell. Physiol. 231: 1870-1875, 2016. © 2015 Wiley

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

    International Nuclear Information System (INIS)

    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

  7. Molecular biology of the renin-angiotensin system

    Energy Technology Data Exchange (ETDEWEB)

    Dzau, V.J.; Burt, D.W.; Pratt, R.E. (Harvard Medical School, Boston, MA (USA))

    1988-10-01

    This paper reviews the molecular biology of the renin-angiotensin system. The renin gene structure is analyzed in detail, including an examination of the putative regulatory regions. The combined action of these regulatory sequences would result in the complex, tissue-specific expression and regulation observed in vivo. The expression of the tissue renin-angiotensin systems, which may have important physiological functions, is also described. In addition, the pathway of renin biosynthesis and secretion is reviewed. This includes speculation on the fate of circulating prorenin and the physiological role of multiple renin forms and secretory pathways. The molecular approaches described in this paper have greatly advanced our knowledge of the biology of the renin-angiotensin system. Future studies using these and other approaches should provide further insight into this complex system.

  8. Applications of membrane computing in systems and synthetic biology

    CERN Document Server

    Gheorghe, Marian; Pérez-Jiménez, Mario

    2014-01-01

    Membrane Computing was introduced as a computational paradigm in Natural Computing. The models introduced, called Membrane (or P) Systems, provide a coherent platform to describe and study living cells as computational systems. Membrane Systems have been investigated for their computational aspects and employed to model problems in other fields, like: Computer Science, Linguistics, Biology, Economy, Computer Graphics, Robotics, etc. Their inherent parallelism, heterogeneity and intrinsic versatility allow them to model a broad range of processes and phenomena, being also an efficient means to solve and analyze problems in a novel way. Membrane Computing has been used to model biological systems, becoming with time a thorough modeling paradigm comparable, in its modeling and predicting capabilities, to more established models in this area. This book is the result of the need to collect, in an organic way, different facets of this paradigm. The chapters of this book, together with the web pages accompanying th...

  9. In vivo cell biology of cancer cells visualized with fluorescent proteins.

    Science.gov (United States)

    Hoffman, Robert M

    2005-01-01

    This chapter describes a new cell biology where the behavior of individual cells can be visualized in the living animal. Previously it has been demonstrated that fluorescent proteins can be used for whole-body imaging of metastatic tumor growth, bacterial infection, and gene expression. An example of the new cell biology is dual-color fluorescence imaging using red fluorescent protein (RFP)-expressing tumors transplanted in green fluorescent protein (GFP)-expressing transgenic mice. These models show with great clarity the details of tumor-stroma interactions and especially tumor-induced angiogenesis, tumor-infiltrating lymphocytes, stromal fibroblasts, and macrophages. Another example is the color coding of cells with RFP or GFP such that both cell types can be simultaneously visualized in vivo. Stem cells can also be visualized and tracked in vivo. Mice in which the regulatory elements of the stem cell marker nestin drive GFP expression enable nascent vasculature to be visualized interacting with transplanted RFP-expressing cancer cells. Nestin-driven GFP expression can also be used to visualize hair follicle stem cells. Dual-color cells expressing GFP in the nucleus and RFP in the cytoplasm enable real-time visualization of nuclear-cytoplasm dynamics including cell cycle events and apoptosis. Highly elongated cancer cells in capillaries in living mice were observed within skin flaps. The migration velocities of the cancer cells in the capillaries were measured by capturing images of the dual-color fluorescent cells over time. The cells in the capillaries elongated to fit the width of these vessels. The use of the dual-color cancer cells differentially labeled in the cytoplasm and nucleus and associated fluorescent imaging provide a powerful tool to understand the mechanism of cancer cell migration and deformation in small vessels.

  10. Predicting biological system objectives de novo from internal state measurements

    Directory of Open Access Journals (Sweden)

    Maranas Costas D

    2008-01-01

    Full Text Available Abstract Background Optimization theory has been applied to complex biological systems to interrogate network properties and develop and refine metabolic engineering strategies. For example, methods are emerging to engineer cells to optimally produce byproducts of commercial value, such as bioethanol, as well as molecular compounds for disease therapy. Flux balance analysis (FBA is an optimization framework that aids in this interrogation by generating predictions of optimal flux distributions in cellular networks. Critical features of FBA are the definition of a biologically relevant objective function (e.g., maximizing the rate of synthesis of biomass, a unit of measurement of cellular growth and the subsequent application of linear programming (LP to identify fluxes through a reaction network. Despite the success of FBA, a central remaining challenge is the definition of a network objective with biological meaning. Results We present a novel method called Biological Objective Solution Search (BOSS for the inference of an objective function of a biological system from its underlying network stoichiometry as well as experimentally-measured state variables. Specifically, BOSS identifies a system objective by defining a putative stoichiometric "objective reaction," adding this reaction to the existing set of stoichiometric constraints arising from known interactions within a network, and maximizing the putative objective reaction via LP, all the while minimizing the difference between the resultant in silico flux distribution and available experimental (e.g., isotopomer flux data. This new approach allows for discovery of objectives with previously unknown stoichiometry, thus extending the biological relevance from earlier methods. We verify our approach on the well-characterized central metabolic network of Saccharomyces cerevisiae. Conclusion We illustrate how BOSS offers insight into the functional organization of biochemical networks

  11. Leakage from biological shield cooling system in Pickering NGS A

    International Nuclear Information System (INIS)

    Over the past eight years, a number of leaks have developed in the Biological Shield Cooling (BSC) system of the Pickering NGS A reactors. The highest leak rate exists in Unit 4. The failure mechanism is not known, but corrosion and/or weld failure are suspected. This paper summarizes the concerns associated with the leaks and possible solutions. It should be noted that the BSC system is peculiar to Pickering A reactors only

  12. Facile: a command-line network compiler for systems biology

    OpenAIRE

    Ollivier Julien F; Siso-Nadal Fernando; Swain Peter S

    2007-01-01

    Abstract Background A goal of systems biology is the quantitative modelling of biochemical networks. Yet for many biochemical systems, parameter values and even the existence of interactions between some chemical species are unknown. It is therefore important to be able to easily investigate the effects of adding or removing reactions and to easily perform a bifurcation analysis, which shows the qualitative dynamics of a model for a range of parameter values. Results We present Facile, a Perl...

  13. The solar system: Importance of research to the biological sciences

    Science.gov (United States)

    Klein, Harold P.

    1992-01-01

    An attempt is made to describe the scope of scientific areas that comprise the current field of exobiology in the United States. From investigations of astrophysical phenomena that deal with the birth of stars and planetary systems to questions of molecular biology involving phylogenetic relationships among organisms, from attempts to simulate the synthesis of biological precursor molecules in the chemistry laboratory to making measurements of the organic constituents of Titan's atmosphere, these researches all converge toward a common objective--answering the question of how life came about in the universe.

  14. The biology of cancer testis antigens: putative function, regulation and therapeutic potential.

    Science.gov (United States)

    Fratta, Elisabetta; Coral, Sandra; Covre, Alessia; Parisi, Giulia; Colizzi, Francesca; Danielli, Riccardo; Nicolay, Hugues Jean Marie; Sigalotti, Luca; Maio, Michele

    2011-04-01

    Cancer testis antigens (CTA) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor-restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor-specific immunotherapeutic approaches, and prompted the development of several clinical trials of CTA-based vaccine therapy. Driven by this practical clinical interest, a more detailed characterization of CTA biology has been recently undertaken. So far, at least 70 families of CTA, globally accounting for about 140 members, have been identified. Most of these CTA are expressed during spermatogenesis, but their function is still largely unknown. Epigenetic events, particularly DNA methylation, appear to be the primary mechanism regulating CTA expression in both normal and transformed cells, as well as in cancer stem cells. In view of the growing interest in CTA biology, the aim of this review is to provide the most recent information on their expression, regulation and function, together with a brief summary of the major clinical trials involving CTA as therapeutic agents. The pharmacologic modulation of CTA expression profiles on neoplastic cells by DNA hypomethylating drugs will also be discussed as a feasible approach to design new combination therapies potentially able to improve the clinical efficacy of currently adopted CTA-based immunotherapeutic regimens in cancer patients.

  15. Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo.

    Science.gov (United States)

    Luker, Gary D

    2002-04-01

    The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.

  16. Somatostatin, somatostatin analogs and somatostatin receptor dynamics in the biology of cancer progression.

    Science.gov (United States)

    Ruscica, M; Arvigo, M; Steffani, L; Ferone, D; Magni, P

    2013-05-01

    The pharmacological effects (i.e., inhibition of endocrine secretion and cell proliferation) mediated by the hormone somatostatin (SRIF) are derived from its universal high-affinity binding to five different G proteincoupled receptors (GPCRs), named sst1-5. However, SRIF has a half-life of less than 3 min, whereas the available mono- and bi-specific SRIF preferential analogs show prolonged half-life and increased potency. These compounds may control tumor development, cell proliferation and metastatization by direct actions, including cell division arrest in G0/G1 phase (i.e., induction of cyclin-dependent kinase inhibitor p27(kip1) or p21(Cip1)), induction of apoptosis (i.e., induction of p53 and Bax) and suppression of cell invasion. Along with these direct actions on the biology of cancer progression, in vivo SRIF analogs may also regulate tumor growth through indirect actions, by suppressing the secretion of growth-promoting hormones and growth factors and angiogenesis. Interestingly, when ssts are co-expressed, they may interact forming homo- or heterodimers, also with other GPCRs such as type 2 dopamine receptor and the μ-opioid receptor 1, altering their original pharmacological and functional properties. Dimers can be not only constitutive, but perhaps also ligandpromoted: hence, compounds with high affinity for different ssts isoforms may be used to achieve effects elicited by specific dimers. Future developments in the knowledge of ssts dynamics upon SRIF and SRIF analogs binding in neoplastic tissues may allow the full elucidation of the pathophysiological role of this system and the exploitation of the therapeutic potential of its modulation.

  17. Exogenous control of biological and ecological systems through evolutionary modelling

    Directory of Open Access Journals (Sweden)

    Alessandro Ferrarini

    2013-09-01

    Full Text Available The controllability of network-like systems is a topical issue in ecology and biology. It relies on the ability to lead a system's behaviour towards the desired state through the appropriate handling of input variables. Up to now, controllability of networks is based on the permanent control of a set of driver nodes that can guide the system's dynamics. This assumption seems motivated by real-world networks observation, where a decentralized control is often applied only to part of the nodes. While in a previous paper I showed that ecological and biological networks can be efficaciously controlled from the inside, here I further introduce a new framework for network controllability based on the employment of exogenous controllers and evolutionary modelling, and provide an exemplification of its application.

  18. Complex fluids in biological systems experiment, theory, and computation

    CERN Document Server

    2015-01-01

    This book serves as an introduction to the continuum mechanics and mathematical modeling of complex fluids in living systems. The form and function of living systems are intimately tied to the nature of surrounding fluid environments, which commonly exhibit nonlinear and history dependent responses to forces and displacements. With ever-increasing capabilities in the visualization and manipulation of biological systems, research on the fundamental phenomena, models, measurements, and analysis of complex fluids has taken a number of exciting directions. In this book, many of the world’s foremost experts explore key topics such as: Macro- and micro-rheological techniques for measuring the material properties of complex biofluids and the subtleties of data interpretation Experimental observations and rheology of complex biological materials, including mucus, cell membranes, the cytoskeleton, and blood The motility of microorganisms in complex fluids and the dynamics of active suspensions Challenges and solut...

  19. Data management in systems biology I - Overview and bibliography

    CERN Document Server

    Mayer, Gerhard

    2009-01-01

    Large systems biology projects can encompass several workgroups often located in different countries. An overview about existing data standards in systems biology and the management, storage, exchange and integration of the generated data in large distributed research projects is given, the pros and cons of the different approaches are illustrated from a practical point of view, the existing software - open source as well as commercial - and the relevant literature is extensively overview, so that the reader should be enabled to decide which data management approach is the best suited for his special needs. An emphasis is laid on the use of workflow systems and of TAB-based formats. The data in this format can be viewed and edited easily using spreadsheet programs which are familiar to the working experimental biologists. The use of workflows for the standardized access to data in either own or publicly available databanks and the standardization of operation procedures is presented. The use of ontologies and...

  20. Systems biology: A tool for charting the antiviral landscape.

    Science.gov (United States)

    Bowen, James R; Ferris, Martin T; Suthar, Mehul S

    2016-06-15

    The host antiviral programs that are initiated following viral infection form a dynamic and complex web of responses that we have collectively termed as "the antiviral landscape". Conventional approaches to studying antiviral responses have primarily used reductionist systems to assess the function of a single or a limited subset of molecules. Systems biology is a holistic approach that considers the entire system as a whole, rather than individual components or molecules. Systems biology based approaches facilitate an unbiased and comprehensive analysis of the antiviral landscape, while allowing for the discovery of emergent properties that are missed by conventional approaches. The antiviral landscape can be viewed as a hierarchy of complexity, beginning at the whole organism level and progressing downward to isolated tissues, populations of cells, and single cells. In this review, we will discuss how systems biology has been applied to better understand the antiviral landscape at each of these layers. At the organismal level, the Collaborative Cross is an invaluable genetic resource for assessing how genetic diversity influences the antiviral response. Whole tissue and isolated bulk cell transcriptomics serves as a critical tool for the comprehensive analysis of antiviral responses at both the tissue and cellular levels of complexity. Finally, new techniques in single cell analysis are emerging tools that will revolutionize our understanding of how individual cells within a bulk infected cell population contribute to the overall antiviral landscape.