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Sample records for cancers molecular biology

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Molecular Biology and Prevention of Endometrial Cancer

    Science.gov (United States)

    2009-07-01

    of the oral contraceptive pill (OCP). Project 1: Objectives completed and data previously submitted with 2004 report. Data published this past year...molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC...not been altered appreciably. Despite the known protective effect of oral contraceptives , little has been learned regarding the underlying mechanism

  6. 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

  7. Molecular biology of breast cancer stem cells: potential clinical applications.

    Science.gov (United States)

    Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

    2010-10-01

    Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy.

  8. 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.

  9. Molecular Biology and Prevention of Endometrial Cancer. Addendum

    Science.gov (United States)

    2008-07-01

    gain insight into the biologic mechanism underlying the chemopreventive effect of the oral contraceptive pill (OCP). Project 1: Objectives completed...oral contraceptive pill and hormone replacement therapy on reproductive organs. This objective has been completed and the results were submitted...protective effect of oral contraceptive (OC) therapy. Methods: 1) Oligonucleotide microarray analysis was performed on a panel of endometrial cancers

  10. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm

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    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.)

  11. 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.

  12. Molecular Cell Biology of Apoptosis and Necroptosis in Cancer.

    Science.gov (United States)

    Dillon, Christopher P; Green, Douglas R

    2016-01-01

    Cell death is a major mechanism to eliminate cells in which DNA is damaged, organelles are stressed, or oncogenes are overexpressed, all events that would otherwise predispose cells to oncogenic transformation. The pathways that initiate and execute cell death are complex, genetically encoded, and subject to significant regulation. Consequently, while these pathways are often mutated in malignancy, there is considerable interest in inducing cell death in tumor cells as therapy. This chapter addresses our current understanding of molecular mechanisms contributing to two cell death pathways, apoptotic cell death and necroptosis, a regulated form of necrotic cell death. Apoptosis can be induced by a wide variety of signals, leading to protease activation that dismantles the cell. We discuss the physiological importance of each apoptosis pathway and summarize their known roles in cancer suppression and the current efforts at targeting each pathway therapeutically. The intricate mechanistic link between death receptor-mediated apoptosis and necroptosis is described, as well as the potential opportunities for utilizing necroptosis in the treatment of malignancy.

  13. 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.

  14. [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.

  15. 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.

  16. Molecular biology and immunology of head and neck cancer.

    Science.gov (United States)

    Guo, Theresa; Califano, Joseph A

    2015-07-01

    In recent years, our knowledge and understanding of head and neck squamous cell carcinoma (HNSCC) has expanded dramatically. New high-throughput sequencing technologies have accelerated these discoveries since the first reports of whole-exome sequencing of HNSCC tumors in 2011. In addition, the discovery of human papillomavirus in relationship with oropharyngeal squamous cell carcinoma has shifted our molecular understanding of the disease. New investigation into the role of immune evasion in HNSCC has also led to potential novel therapies based on immune-specific systemic therapies.

  17. Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment.

    Science.gov (United States)

    Teoh, Seong Lin; Das, Srijit

    2016-11-01

    Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.

  18. Biologia molecular do câncer cervical Molecular biology of cervical cancer

    Directory of Open Access Journals (Sweden)

    Waldemar Augusto Rivoire

    2006-01-01

    Full Text Available A carcinogênese é um processo de múltiplas etapas. Alterações no equilíbrio citogenético ocorrem na transformação do epitélio normal a câncer cervical. Numerosos estudos apoiam a hipótese de que a infecção por HPV está associada com o desenvolvimento de alterações malignas e pré-malignas do trato genital inferior. Neste trabalho são apresentadas as bases para a compreensão da oncogênese cervical. O ciclo celular é controlado por proto-oncogenes e genes supressores. Quando ocorrem mutações, proto-oncogenes tornam-se oncogenes, que são carcinogênicos e causam multiplicação celular excessiva. A perda da ação de genes supressores funcionais pode levar a célula ao crescimento inadequado. O ciclo celular também pode ser alterado pela ação de vírus, entre eles o HPV (Human Papiloma Virus, de especial interesse na oncogênese cervical. Os tipos de HPV 16 e 18 são os de maior interesse, freqüentemente associados a câncer cervical e anal. O conhecimento das bases moleculares que estão envolvidas na oncogênese cervical tem sido possível devido a utilização de técnicas avançadas de biologia molecular. A associação destas técnicas aos métodos diagnósticos clássicos, poderão levar a uma melhor avaliação das neoplasias cervicais e auxiliar no desenvolvimento de novas terapias, talvez menos invasivas e mais efetivas.Carcinogenesis involves several steps. Disorders of the cytogenetic balance occur during the evolution from normal epithelium to cervical cancer. Several studies support the hypothesis that the Human Papiloma Virus (HPV infection is associated to development of premalignant and malignant lesions of cervical cancer. In this review we show the basis to understand cervical oncogenesis. The cell cycle is controlled by protooncogenes and supressive genes. This orchestrated cell cycle can be affected by virus such as HPV. Of special interest in the cervical carcinogenesis are the HPV subtypes 16 and 18

  19. Individualized treatment of gastric cancer:Impact of molecular biology and pathohistological features

    Institute of Scientific and Technical Information of China (English)

    Yves; Dittmar; Utz; Settmacher

    2015-01-01

    Gastric cancer is one of the most common malignancies worldwide.The overall prognosis remains poor over the last decades even though improvements in surgical outcomes have been achieved.A better understanding of the molecular biology of gastric cancer and detection of eligible molecular targets might be of central interest to further improve clinical outcome.With this intention,first steps have been made in the research of growth factor signaling.Regarding morphogens,cell cycle and nuclear factor-κB signaling,a remarkable count of target-specific agents have been developed,nevertheless the transfer into the field of clinical routine is still at the beginning.The potential utility of epigenetic targets and the further evaluation of micro RNA signaling seem to have potential for the development of novel treatment strategies in the future.

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

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    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.

  1. 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.

  2. 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.

  3. Translating clinical research of Molecular Biology into a personalized, multidisciplinary approach of colorectal cancer patients.

    Science.gov (United States)

    Strambu, V; Garofil, D; Pop, F; Radu, P; Bratucu, M; Popa, F

    2014-03-15

    Although multimodal treatment has brought important benefit, there is still great heterogeneity regarding the indication and response to chemotherapy in Stage II and III, and individual variations related to both overall survival and toxicity of new therapies in metastatic disease or tumor relapse. Recent research in molecular biology led to the development of a large scale of genetic biomarkers, but their clinical use is not concordant with the high expectations. The Aim of this review is to identify and discuss the molecular markers with proven clinical applicability as prognostic and/or predictive factors in CRC and also to establish a feasible algorithm of molecular testing, as routine practice, in the personalized, multidisciplinary approach of colorectal cancer patients in our country. Despite the revolution that occurred in the field of molecular marker research, only Serum CEA, Immunohistochemical analysis of mismatch repair proteins and PCR testing for KRAS and BRAF mutations have confirmed their clinical utility in the management of colorectal cancer. Their implementation in the current practice should partially resolve some of the controversies related to this heterogenic pathology, in matters of prognosis in different TNM stages, stage II patient risk stratification, diagnosis of hereditary CRC and likelihood of benefit from anti EGFR therapy in metastatic disease. The proposed algorithms of molecular testing are very useful but still imperfect and require further validation and constant optimization.

  4. Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

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    Min, Jung Joon; Nguyen, Vu H. [Chonnam National University Medical School, Gwangju (Korea, Republic of); Gambhir, Sanjiv S. [Stanford University, California(United States)

    2010-04-15

    Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonarrival biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.

  5. KRAS and BRAF Mutation Detection: Is Immunohistochemistry a Possible Alternative to Molecular Biology in Colorectal Cancer?

    Directory of Open Access Journals (Sweden)

    Nicolas Piton

    2015-01-01

    Full Text Available KRAS genotyping is mandatory in metastatic colorectal cancer treatment prior to undertaking antiepidermal growth factor receptor (EGFR monoclonal antibody therapy. BRAF V600E mutation is often present in colorectal carcinoma with CpG island methylator phenotype and microsatellite instability. Currently, KRAS and BRAF evaluation is based on molecular biology techniques such as SNaPshot or Sanger sequencing. As molecular testing is performed on formalin-fixed paraffin-embedded (FFPE samples, immunodetection would appear to be an attractive alternative for detecting mutations. Thus, our objective was to assess the validity of KRAS and BRAF immunodetection of mutations compared with the genotyping reference method in colorectal adenocarcinoma. KRAS and BRAF genotyping was assessed by SNaPshot. A rabbit anti-human KRAS polyclonal antibody was tested on 33 FFPE colorectal tumor samples with known KRAS status. Additionally, a mouse anti-human BRAF monoclonal antibody was tested on 30 FFPE tumor samples with known BRAF status. KRAS immunostaining demonstrated both poor sensitivity (27% and specificity (64% in detecting KRAS mutation. Conversely, BRAF immunohistochemistry showed perfect sensitivity (100% and specificity (100% in detecting V600E mutation. Although molecular biology remains the reference method for detecting KRAS mutation, immunohistochemistry could be an attractive method for detecting BRAF V600E mutation in colorectal cancer.

  6. KRAS and BRAF Mutation Detection: Is Immunohistochemistry a Possible Alternative to Molecular Biology in Colorectal Cancer?

    Science.gov (United States)

    Piton, Nicolas; Borrini, Francesco; Bolognese, Antonio; Lamy, Aude; Sabourin, Jean-Christophe

    2015-01-01

    KRAS genotyping is mandatory in metastatic colorectal cancer treatment prior to undertaking antiepidermal growth factor receptor (EGFR) monoclonal antibody therapy. BRAF V600E mutation is often present in colorectal carcinoma with CpG island methylator phenotype and microsatellite instability. Currently, KRAS and BRAF evaluation is based on molecular biology techniques such as SNaPshot or Sanger sequencing. As molecular testing is performed on formalin-fixed paraffin-embedded (FFPE) samples, immunodetection would appear to be an attractive alternative for detecting mutations. Thus, our objective was to assess the validity of KRAS and BRAF immunodetection of mutations compared with the genotyping reference method in colorectal adenocarcinoma. KRAS and BRAF genotyping was assessed by SNaPshot. A rabbit anti-human KRAS polyclonal antibody was tested on 33 FFPE colorectal tumor samples with known KRAS status. Additionally, a mouse anti-human BRAF monoclonal antibody was tested on 30 FFPE tumor samples with known BRAF status. KRAS immunostaining demonstrated both poor sensitivity (27%) and specificity (64%) in detecting KRAS mutation. Conversely, BRAF immunohistochemistry showed perfect sensitivity (100%) and specificity (100%) in detecting V600E mutation. Although molecular biology remains the reference method for detecting KRAS mutation, immunohistochemistry could be an attractive method for detecting BRAF V600E mutation in colorectal cancer.

  7. [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.

  8. Sec62 bridges the gap from 3q amplification to molecular cell biology in non-small cell lung cancer.

    Science.gov (United States)

    Linxweiler, Maximilian; Linxweiler, Johannes; Barth, Monika; Benedix, Julia; Jung, Volker; Kim, Yoo-Jin; Bohle, Rainer M; Zimmermann, Richard; Greiner, Markus

    2012-02-01

    The molecular carcinogenesis of lung cancer has yet to be clearly elucidated. We investigated the possible oncogenic function of SEC62 in lung cancer, which was predicted based on our previous findings that lung and thyroid cancer tissue samples exhibited increased Sec62 protein levels. The SEC62 gene locus is at 3q26.2, and 3q amplification is reportedly the most common genomic alteration in non-small cell lung cancer. We analyzed SEC62 mRNA and protein levels in tissue samples from lung cancer patients by real-time quantitative PCR, Western blot, and IHC and found significantly increased SEC62 mRNA and protein levels in tumors compared with tumor-free tissue samples from the same patients. Correlation analyses revealed significantly higher Sec62 levels in tumors with lymph node metastases compared with nonmetastatic tumors, as well as in poorly compared with moderately differentiated tumors. On the basis of these promising results, we examined the role of Sec62 in cancer cell biology in vitro. Cell migration assays with lung and thyroid cancer cells showed distinct stimulation of migration in SEC62-overexpressing cells and inhibition of migration in Sec62-depleted cells. Moreover, we found that SEC62 silencing sensitized the cells to thapsigargin-induced endoplasmic reticulum stress. Thus, our results indicate that SEC62 represents a potential candidate oncogene in the amplified 3q region in cases of non-small cell lung cancer and harbors various functions in cancer cell biology.

  9. Molecular Biology of Esophageal Cancer%食管癌的分子生物学

    Institute of Scientific and Technical Information of China (English)

    Huan Xi; Jan Brabender; Ralf Metzger; Paul M.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.

  10. Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

    Science.gov (United States)

    San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

    2014-12-01

    Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA.

  11. Molecular PET imaging for biology-guided adaptive radiotherapy of head and neck cancer.

    Science.gov (United States)

    Hoeben, Bianca A W; Bussink, Johan; Troost, Esther G C; Oyen, Wim J G; Kaanders, Johannes H A M

    2013-10-01

    Integration of molecular imaging PET techniques into therapy selection strategies and radiation treatment planning for head and neck squamous cell carcinoma (HNSCC) can serve several purposes. First, pre-treatment assessments can steer decisions about radiotherapy modifications or combinations with other modalities. Second, biology-based objective functions can be introduced to the radiation treatment planning process by co-registration of molecular imaging with planning computed tomography (CT) scans. Thus, customized heterogeneous dose distributions can be generated with escalated doses to tumor areas where radiotherapy resistance mechanisms are most prevalent. Third, monitoring of temporal and spatial variations in these radiotherapy resistance mechanisms early during the course of treatment can discriminate responders from non-responders. With such information available shortly after the start of treatment, modifications can be implemented or the radiation treatment plan can be adapted tailing the biological response pattern. Currently, these strategies are in various phases of clinical testing, mostly in single-center studies. Further validation in multicenter set-up is needed. Ultimately, this should result in availability for routine clinical practice requiring stable production and accessibility of tracers, reproducibility and standardization of imaging and analysis methods, as well as general availability of knowledge and expertise. Small studies employing adaptive radiotherapy based on functional dynamics and early response mechanisms demonstrate promising results. In this context, we focus this review on the widely used PET tracer (18)F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

  12. Molecular biology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.

    Science.gov (United States)

    Nana-Sinkam, Serge Patrick; Powell, Charles A

    2013-05-01

    Based on recent bench and clinical research, the treatment of lung cancer has been refined, with treatments allocated according to histology and specific molecular features. For example, targeting mutations such as epidermal growth factor receptor (EGFR) with tyrosine kinase inhibitors has been particularly successful as a treatment modality, demonstrating response rates in selected patients with adenocarcinoma tumors harboring EGFR mutations that are significantly higher than those for conventional chemotherapy. However, the development of new targeted therapies is, in part, highly dependent on an improved understanding of the molecular underpinnings of tumor initiation and progression, knowledge of the role of molecular aberrations in disease progression, and the development of highly reproducible platforms for high-throughput biomarker discovery and testing. In this article, we review clinically relevant research directed toward understanding the biology of lung cancer. The clinical purposes of this research are (1) to identify susceptibility variants and field molecular alterations that will promote the early detection of tumors and (2) to identify tumor molecular alterations that serve as therapeutic targets, prognostic biomarkers, or predictors of tumor response. We focus on research developments in the understanding of lung cancer somatic DNA mutations, chromosomal aberrations, epigenetics, and the tumor microenvironment, and how they can advance diagnostics and therapeutics.

  13. Descriptive Epidemiology, Molecular Biology and Genetics of Hereditary Prostate Cancer in Denmark

    DEFF Research Database (Denmark)

    Bentzon, Diem Nguyen

    2012-01-01

    A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer.......A search for markers that can differentiate indolent prostate cancers from more aggressive forms. Assessment of clinical differences between hereditary and sporadicc prostate cancer....

  14. B-Raf mutation: a key player in molecular biology of cancer.

    Science.gov (United States)

    Rahman, M A; Salajegheh, A; Smith, R A; Lam, A K-Y

    2013-12-01

    B-Raf is one of the more commonly mutated proto-oncogenes implicated in the development of cancers. In this review, we consider the mechanisms and clinical impacts of B-Raf mutations in cancer and discuss the implications for the patient in melanoma, thyroid cancer and colorectal cancer, where B-Raf mutations are particularly common.

  15. [Tuberculosis and molecular biology].

    Science.gov (United States)

    Andersen, Ase Bengård; Lillebaek, Troels; Søborg, Christian; Johansen, Isik Somuncu; Thomsen, Vibeke Østergaard

    2003-02-24

    Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) hunting millions worldwide, is a challenge to work with in the laboratory. Modern molecular biology has provided extremely useful tools which have changed conventional diagnostic procedures in the TB laboratories. Research in molecular epidemiology is currently expanding our knowledge of the natural history of TB. Access to the genome sequence has opened new avenues for research in drug development and new vaccines. However, we are still awaiting the impact of these efforts in the resource-poor TB endemic countries.

  16. Topology in Molecular Biology

    CERN Document Server

    Monastyrsky, Michail Ilych

    2007-01-01

    The book presents a class of new results in molecular biology for which topological methods and ideas are important. These include: the large-scale conformation properties of DNA; computational methods (Monte Carlo) allowing the simulation of large-scale properties of DNA; the tangle model of DNA recombination and other applications of Knot theory; dynamics of supercoiled DNA and biocatalitic properties of DNA; the structure of proteins; and other very recent problems in molecular biology. The text also provides a short course of modern topology intended for the broad audience of biologists and physicists. The authors are renowned specialists in their fields and some of the new results presented here are documented for the first time in monographic form.

  17. Targeted Therapy Database (TTD: a model to match patient's molecular profile with current knowledge on cancer biology.

    Directory of Open Access Journals (Sweden)

    Simone Mocellin

    Full Text Available BACKGROUND: The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. OBJECTIVE: To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. METHODS: To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. RESULTS AND CONCLUSIONS: We created a manually annotated database (Targeted Therapy Database, TTD where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method

  18. Biologic Therapy (Immunotherapy) for Kidney Cancer

    Science.gov (United States)

    ... Stage for Kidney Cancer Kidney Cancer Treating Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer The goal of biologic therapy ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  19. Molecular biology of potyviruses.

    Science.gov (United States)

    Revers, Frédéric; García, Juan Antonio

    2015-01-01

    Potyvirus is the largest genus of plant viruses causing significant losses in a wide range of crops. Potyviruses are aphid transmitted in a nonpersistent manner and some of them are also seed transmitted. As important pathogens, potyviruses are much more studied than other plant viruses belonging to other genera and their study covers many aspects of plant virology, such as functional characterization of viral proteins, molecular interaction with hosts and vectors, structure, taxonomy, evolution, epidemiology, and diagnosis. Biotechnological applications of potyviruses are also being explored. During this last decade, substantial advances have been made in the understanding of the molecular biology of these viruses and the functions of their various proteins. After a general presentation on the family Potyviridae and the potyviral proteins, we present an update of the knowledge on potyvirus multiplication, movement, and transmission and on potyvirus/plant compatible interactions including pathogenicity and symptom determinants. We end the review providing information on biotechnological applications of potyviruses.

  20. [Biology molecular of glioblastomas].

    Science.gov (United States)

    Franco-Hernández, C; Martínez-Glez, V; Rey, J A

    2007-10-01

    Glioblastomas, the most frequent and malignant human brain tumors, may develop de novo (primary glioblastoma) or by progression from low-grade or anapalsic astrocytoma (secondary glioblastoma). The molecular alteration most frequent in these tumor-like types is the loss of heterozygosity on chromosome 10, in which several genes have been identified as tumors suppressor. The TP53/MDM2/P14arf and CDK4/RB1/ P16ink4 genetic pathways involved in cycle control are deregulated in the majority of gliomas as well as genes that promote the cellular division, EGFR. Finally the increase of growth and angiogenics factors is also involved in the development of glioblastomas. One of the objectives of molecular biology in tumors of glial ancestry is to try to find the genetic alterations that allow to approach better the classification of glioblastomas, its evolution prediction and treatment. The new pathmolecular classification of gliomas should improve the old one, especially being concerned about the oncogenesis and heterogeneity of these tumors. It is desirable that this classification had clinical applicability and integrates new molecular findings with some known histological features with pronostic value. In this paper we review the most frequent molecular mechanisms involved in the patogenesis of glioblastomas.

  1. 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.

  2. Molecular biology from bench-to-bedside - which colorectal cancer patients should be referred for genetic counselling and risk assessment

    DEFF Research Database (Denmark)

    Jensen, Lars Henrik; Dysager, Lars; Lindebjerg, Jan

    2010-01-01

    was to validate our previously suggested clinically applicable strategy based on molecular characteristics for identifying which patients to refer for genetic counselling. The strategy was validated in an unselected cohort of 287 colorectal cancer patients. All tumours were tested for MLH1, PMS2, MSH2 and MSH6...... with hereditary cancer. It is feasible to perform a molecular screening to select patients for genetic counselling....

  3. Genes to vaccines for immunotherapy: how the molecular biology revolution has influenced cancer immunology.

    Science.gov (United States)

    Laheru, Dan A; Pardoll, Drew M; Jaffee, Elizabeth M

    2005-11-01

    Recent advances in our understanding of the complex signaling pathways involved in immune system regulation, along with analyses of genetic differences between tumors and their normal cellular counterparts, have accelerated development of immune-based strategies for cancer treatment and prevention. More clinically relevant animal models have shown that successful immune-based strategies will require the integration of interventions that target specific tumor antigens with regulators of the antitumor immune response. Immunotherapy for cancer is at a critical crossroad, as therapeutics designed to target cancer-associated antigens and regulatory signaling molecules enter clinical trials. We outline here a paradigm for early-stage clinical development of immunotherapy combinations that use vaccines to drive tumor antigen-specific responses while simultaneously targeting immune regulatory pathways.

  4. Molecular Biology of Nitrogen Fixation

    Science.gov (United States)

    Shanmugam, K. T.; Valentine, Raymond C.

    1975-01-01

    Reports that as a result of our increasing knowledge of the molecular biology of nitrogen fixation it might eventually be possible to increase the biological production of nitrogenous fertilizer from atmospheric nitrogen. (GS)

  5. Engineering Nanoscale Biological Molecular Motors

    OpenAIRE

    Korosec, Chapin; Forde, Nancy R.

    2017-01-01

    Understanding the operation of biological molecular motors, nanoscale machines that transduce electrochemical energy into mechanical work, is enhanced by bottom-up strategies to synthesize novel motors.

  6. Molecular control of the cell cycle in cancer: biological and clinical aspects

    DEFF Research Database (Denmark)

    Møller, Michael Boe

    2003-01-01

    The RB1 pathway and the p53 pathway represent important, interconnected biochemical units frequently perturbed in human cancer. Essential tumor protective mechanisms, such as cellular growth control and apoptosis, are regulated through these systems. Comprehensive studies of these pathways...... to treatment. Chemotherapeutic regimens used in lymphoma treatment are based on apoptosis induction, and as both E2F-1 and p53 are regulators of apoptosis, it is possible that the observed treatment failure is associated with reduced E2F-1- and p53-mediated apoptosis. Survival analyses revealed numerous novel...

  7. Biologia molecular do câncer colorretal: uma revolução silenciosa em andamento Molecular biology of colorectal cancer: a silent revolution

    Directory of Open Access Journals (Sweden)

    Mauro de Souza Leite Pinho

    2008-09-01

    Full Text Available Embora os estudos sobre biologia molecular permaneçam como a principal expectativa para o surgimento de novos conceitos e recursos para o tratamento do câncer colorretal, a ausência de resultados de real impacto do ponto de vista clínico ao longo dos últimos anos podem representar uma frustração para quem não esteja acompanhando de perto a evolução das pesquisas nesta área. Assim sendo, nosso objetivo no presente texto é apresentar uma breve revisão do caminho percorrido até o momento desde os trabalhos pioneiros sobre carcinogênese colorretal até as pesquisas mais recentes sobre proteômica, demonstrando assim o constante fluxo de grandes avanços os quais possibilitam uma previsão realista a curto ou médio prazo da disponibilização de recursos de amplo impacto, com potencial para alterar de forma relevante os resultados do tratamento desta importante doença.Despite remaining as the main hope for emerging new concepts and strategies for treatment of colorectal cancer, the lack of results with clinical impact over the last years may contribute to frustrate those not entirely aware about current research data. So, the aim of this paper is to present a brief review since the first molecular biology studies in colorectal carcinogenesis until recent advances in proteomics, in order to demonstrate the consistent production of new data supporting a realistic expectancy for a near future availability of high impact resources that may change dramatically the results of treatment of colorectal cancer.

  8. Ultrastructure and molecular biological changes of chronic gastritis, gastric cancer and gastric precancerous lesions: a comparative study

    Institute of Scientific and Technical Information of China (English)

    Goang-Yao Yin; Wu-Ning Zhang; Xiao-Jing Shen; Yi Chen; Xue-Fen He

    2003-01-01

    AIM: To carry out a comparative study on ultrastructure and molecular biological changes of chronic gastritis (CG),gastric cancer (GC) aand gastric precancerous lesions.METHODS: By the use of histochemical staining, SEM with EDAX, TEM with EDAX, image analysis technique, RIA and chemiluminescence method, gastric mucosa of 168 patients were synchronously analyzed in morphology, trace elements, DNA, cAMP, SOD, 3H-TdR LCT and serum LPO were also done.RESULTS: The incidence of epithelial nucleoplasmic ratio >1, lobulated nuclei, inter-chromatin aggregation of granules, nucleolar hypertrophy, and the content of DNA,Zn, Cu in nuclei and serum LPO of each group were showed as belows: normal control group (0.0, 0.0, 6.7, 0.0, 12.6±2.7,7.6±0.4, 58.4±0.3, 2.6±0.6), CSG group (5.7, 2.9, 7.4, 2.9,15.2±3.1, 8.1±0.5, 58.9±0.5, 4.2±0.7), CAG group (31.3,29.7, 45.3, 42.2, 16.5±3.1, 8.6±0.4, 59.3±0.5, 4.5±0.6), CA group (100.0, 100.0, 72.2, 50.0, 30.7±8.2, 8.8±0.3, 59.5±0.4,6.8±1.6), ATP++group (61.5, 38.5, 23.1, 38.5, 23.5±8.9,8.3±0.4, 59.1±0.4, 5.1±1.2), IM+++ ATP++group (77.8, 55.5,33.3, 44.4, 25.1±7.2, 8.4±0.5, 59.5±0.4, 6.5±1.1),IM++++ATP++ group (100.0, 100.0, 75.0, 62.5, 28.5±9.1,8.9±0.5, 59.7±0.4, 7.6±0.7), IMⅡb group (100.0, 62.5, 75.0,50.0, 27.3±10.3, 8.6±0.3, 59.5±0.4, 6.1±0.9); whereas the content of Zn, Cu in mitochondria and cAMP, SOD in gastric mucosa, and 3H-TdR LCT of each group were showen as belows: normal control group (9.2±0.5, 58.3±0.3, 15.9±1.5,170.5±6.1, 1079.7±227.4), CSG group (8.6±0.5, 57.8±0.3,14.6±1.8, 163.3±5.6, 867.3±240.5), CAG group (8.3±0.4,57.5±0.3, 13.4±1.8, 161.2±4.3, 800.9±221.8), CA group (8.9±0.4, 57.1±0.3, 10.2±3.9, 152.2±3.8, 325.7±186.8),ATP++ group (9.1±0.4, 57.0±0.3, 12.4±1.8, 161.5±3.8,642.9±174.3), IM+++ ATP++ group (8.6±0.4, 56.9±0.3,12.0±2.3, 152.2±2.5, 326.3±160.3), IM++++ATP++ group (8.5±0.3, 56.8±0.2, 10.4±0.9, 147.4±2.6, 316.1±170.7),IMⅡb group (8.6±0.3, 56

  9. Bilingual teaching of molecular biology

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Recently bilingual teaching in China's universities has been widely carried out and become a popular subject for study. In this paper, the reasons for bilingual teaching of molecular biology are pointed out, the textbook of molecular biology and teaching method in bilingual teaching classes are determined after investigation and the practice of bilingually teaching molecular biology use both English and Chinese in a class. The effect has proved good. The bilingual teaching methods, the problem of bilingual teaching, the importance of understanding its significance and the possibilities of improving such teaching of the subject are also discussed.

  10. Biomolecular Architectures Molecular Biology

    Science.gov (United States)

    2013-08-31

    designed molecular beacon probes for detecting hlyA and invA genes from Listeria monocytogenes (Gram-positive) and Salmonella spp . (Gram-negative...bacterium, Bacillus thuringiensis, transgenic tobacco containing the transgene, Bt cry1Ac, the Gram-negative bacterium, Salmonella Typhimurium, and the Gram... Salmonella Typhimurium, and the Gram-positive bacterium, Listeria monocytogenes, were monitored for detection by coupling molecular beacon (MB

  11. Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer.

    Science.gov (United States)

    Rooney, Claire; Sethi, Tariq

    2015-10-01

    Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease.

  12. Molecular biology of hearing [

    Directory of Open Access Journals (Sweden)

    Diensthuber, Marc

    2012-04-01

    Full Text Available [english] The inner ear is our most sensitive sensory organ and can be subdivided into three functional units: organ of Corti, stria vascularis and spiral ganglion. The appropriate stimulus for the organ of hearing is sound, which travels through the external auditory canal to the middle ear where it is transmitted to the inner ear. The inner ear houses the hair cells, the sensory cells of hearing. The inner hair cells are capable of mechanotransduction, the transformation of mechanical force into an electrical signal, which is the basic principle of hearing. The stria vascularis generates the endocochlear potential and maintains the ionic homeostasis of the endolymph. The dendrites of the spiral ganglion form synaptic contacts with the hair cells. The spiral ganglion is composed of neurons that transmit the electrical signals from the cochlea to the central nervous system. In recent years there has been significant progress in research on the molecular basis of hearing. An increasing number of genes and proteins related to hearing are being identified and characterized. The growing knowledge of these genes contributes not only to greater appreciation of the mechanism of hearing but also to a deeper understanding of the molecular basis of hereditary hearing loss. This basic research is a prerequisite for the development of molecular diagnostics and novel therapies for hearing loss.

  13. Aplicación de las técnicas de biología molecular en oncología oral Application of molecular biology techniques in oral cancer

    Directory of Open Access Journals (Sweden)

    M. López-Durán

    2010-08-01

    Full Text Available Este artículo de revisión se propone exponer las principales técnicas de biología molecular disponibles actualmente para los investigadores, en el campo del cáncer y precáncer oral, clasificadas según el tipo de material biológico del que se disponga para iniciar la investigación. Éste puede ser ADN, ARN o proteínas. La explicación de cada técnica comprenderá una breve sistemática del proceso, así como sus ventajas, inconvenientes y estado de actividad actual. Todo ello con la finalidad de esclarecer las aplicaciones, pronto indispensables, de las técnicas más destacadas, en el diagnóstico precoz, pronóstico y tratamiento individualizado del carcinoma oral. Entre las técnicas más útiles en este proceso se encuentran: la electroforesis en gel, las técnicas de hibridación, la tecnología microarray, los biochips, la PCR convencional, la cuantitativa o la transcriptasa inversa, las técnicas de Southern, Northern y Western blot, la secuenciación de ADN, la clonación de genes, la inmunohistoquímica, el ensayo ELISA y la citometría de flujo. Destacan en particular por su gran utilidad, la tecnología microarray, los biochips y la PCR.This article summarizes the main techniques in the area of molecular biology that are available for the investigation of oral cancer and precancer. They have been classified depending on the biological material we expect to analyze, which can be DNA, RNA or proteins. The explanation for each technique includes a brief description of its basics, as well as some advantages, drawbacks and current use of the technique. Our aim is to throw light on the applications of these techniques, soon indispensable for most studies, in the early diagnosis, prognosis and individualized treatment of oral carcinoma. The most useful techniques for this objective are nowadays: gel electrophoresis, hybridation, microarray technology, biochips, PCR (conventional, quantitative or reverse transcriptase, Southern

  14. Treatment algorithm in 2014 for advanced non-small cell lung cancer: therapy selection by tumour histology and molecular biology.

    Science.gov (United States)

    Manegold, Christian

    2014-09-01

    The availability of antineoplastic monoclonal antibodies, small molecules and newer cytotoxics such as pemetrexed, the EGFR-tyrosine kinase inhibitors erlotinib, gefitinib, afatinib as well as the anti-angiogenic bevacizumab and the ALK-inhibitor crizotinib has recently changes the treatment algorithm of advanced non-small cell lung cancer. Decision making in 2014 is characterized by customizing therapy, by selecting a specific therapeutic regimen based on the histotype and the genotype of the tumour. This refers to first-line induction therapy and maintenance therapy as well, but also to subsequent lines of therapy since anti-neoplastic drugs and regimens used upfront clinically influence the selection of agents/regimes considered for second-/third-line treatment. Consequently, therapy customization through tumour histology and molecular markers has significantly influenced the work of pathologists around the globe and the process of obtaining an extended therapeutically relevant tumour diagnosis. Not only histological sub-typing became standard but molecular information is also considered of increasing importance for treatment selection. Routine molecular testing in certified laboratories must be established, and the diagnostic process should ideally be performed under the guidance of evidence based recommendation. The process of investigating and implementing medical targeting in lung cancer therefore, requires advanced diagnostic techniques and expertise and because of its large dimension is costly and influenced by the limitation of financial and clinical resources.

  15. 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.

  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. Genitourinary cancers: molecular determinants for personalized therapies.

    Science.gov (United States)

    Mazzucchelli, Roberta; Gasparrini, Silvia; Galosi, Andrea B; Massari, Francesco; Raspollini, Maria Rosaria; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2016-09-26

    Recent insights and emerging strategies for individualized therapeutic approaches in patients with genitourinary (GU) cancers are based on patient's genomic and cancer's molecular profiles. This depends on the significant advances made in molecular biology technologies, such as next-generation sequencing and whole-exome sequencing. The rise of such novel techniques has grayly increased our knowledge on cancer cell biology and development, thus allowing to identify complex abnormalities at the genomic level. These findings have paved the way toward what is called precision medicine, thus providing healthcare from an individual perspective in patients with GU tumors.

  18. Molecular Processes in Biological Thermosensation

    Directory of Open Access Journals (Sweden)

    I. Digel

    2008-01-01

    Full Text Available Since thermal gradients are almost everywhere, thermosensation could represent one of the oldest sensory transduction processes that evolved in organisms. There are many examples of temperature changes affecting the physiology of living cells. Almost all classes of biological macromolecules in a cell (nucleic acids, lipids, proteins can present a target of the temperature-related stimuli. This review discusses some features of different classes of temperature-sensing molecules as well as molecular and biological processes that involve thermosensation. Biochemical, structural, and thermodynamic approaches are applied in the paper to organize the existing knowledge on molecular mechanisms of thermosensation. Special attention is paid to the fact that thermosensitive function cannot be assigned to any particular functional group or spatial structure but is rather of universal nature. For instance, the complex of thermodynamic, structural, and functional features of hemoglobin family proteins suggests their possible accessory role as “molecular thermometers”.

  19. Skin Cancer: Biology, Risk Factors & Treatment

    Science.gov (United States)

    ... turn Javascript on. Feature: Skin Cancer Skin Cancer: Biology, Risk Factors & Treatment Past Issues / Summer 2013 Table ... Articles Skin Cancer Can Strike Anyone / Skin Cancer: Biology, Risk Factors & Treatment / Timely Healthcare Checkup Catches Melanoma ...

  20. Molecular biology of the cell

    CERN Document Server

    Alberts, Bruce; Lewis, Julian

    2000-01-01

    Molecular Biology of the Cell is the classic in-dept text reference in cell biology. By extracting the fundamental concepts from this enormous and ever-growing field, the authors tell the story of cell biology, and create a coherent framework through which non-expert readers may approach the subject. Written in clear and concise language, and beautifully illustrated, the book is enjoyable to read, and it provides a clear sense of the excitement of modern biology. Molecular Biology of the Cell sets forth the current understanding of cell biology (completely updated as of Autumn 2001), and it explores the intriguing implications and possibilities of the great deal that remains unknown. The hallmark features of previous editions continue in the Fourth Edition. The book is designed with a clean and open, single-column layout. The art program maintains a completely consistent format and style, and includes over 1,600 photographs, electron micrographs, and original drawings by the authors. Clear and concise concept...

  1. Preliminary research on regulatory effect of estrogen on malignant biological behaviors of triple-negative breast cancer cells and its molecular mechanisms

    Institute of Scientific and Technical Information of China (English)

    Tian-Fang Zhou

    2016-01-01

    Objective:To study the regulating effect of estrogen on malignant biological behaviors of triple-negative breast cancer cells and its molecular mechanisms. Methods:Triple-negative breast cancer cell lines MDA-MB-468 were cultured and treated with different doses of estrogen and 10-6 mol/L estrogen combined with GPR30 antagonist G15 for 12 h, 24 h and 48 h, and then cell viability, migration as well as mRNA expression levels of ITGβ1, Sema 4D, MK, c-Met and AEG-1 were detected. Results:Estradiol could increase cell viability, reduce scratch area and increase mRNA expression levels of ITGβ1, Sema 4D, MK, c-Met and AEG-1 in dose-dependent and time-dependent manner;after estradiol combined with G15 treatment, cell viability was significantly lower than that of estradiol treatment alone, scratch area was significantly larger than that of estradiol treatment alone, and mRNA contents of ITGβ1, Sema 4D, MK, c-Met and AEG-1 were significantly lower than those of estradiol treatment alone. Conclusion:Estrogen can regulate the malignant biological behaviors of triple-negative breast cancer cells, promote cell proliferation and migration, and increase the expression of related genes through GPR30.

  2. Biological and Molecular Effects of Small Molecule Kinase Inhibitors on Low-Passage Human Colorectal Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Falko Lange

    2014-01-01

    Full Text Available Low-passage cancer cell lines are versatile tools to study tumor cell biology. Here, we have employed four such cell lines, established from primary tumors of colorectal cancer (CRC patients, to evaluate effects of the small molecule kinase inhibitors (SMI vemurafenib, trametinib, perifosine, and regorafenib in an in vitro setting. The mutant BRAF (V600E/V600K inhibitor vemurafenib, but also the MEK1/2 inhibitor trametinib efficiently inhibited DNA synthesis, signaling through ERK1/2 and expression of genes downstream of ERK1/2 in BRAF mutant cells only. In case of the AKT inhibitor perifosine, three cell lines showed a high or intermediate responsiveness to the drug while one cell line was resistant. The multikinase inhibitor regorafenib inhibited proliferation of all CRC lines with similar efficiency and independent of the presence or absence of KRAS, BRAF, PIK3CA, and TP53 mutations. Regorafenib action was associated with broad-range inhibitory effects at the level of gene expression but not with a general inhibition of AKT or MEK/ERK signaling. In vemurafenib-sensitive cells, the antiproliferative effect of vemurafenib was enhanced by the other SMI. Together, our results provide insights into the determinants of SMI efficiencies in CRC cells and encourage the further use of low-passage CRC cell lines as preclinical models.

  3. Molecular imaging of prostate cancer with PET.

    Science.gov (United States)

    Jadvar, Hossein

    2013-10-01

    Molecular imaging is paving the way for precision and personalized medicine. In view of the significant biologic and clinical heterogeneity of prostate cancer, molecular imaging is expected to play an important role in the evaluation of this prevalent disease. The natural history of prostate cancer spans from an indolent localized process to biochemical relapse after radical treatment with curative intent to a lethal castrate-resistant metastatic disease. The ongoing unraveling of the complex tumor biology of prostate cancer uniquely positions molecular imaging with PET to contribute significantly to every clinical phase of prostate cancer evaluation. The purpose of this article was to provide a concise review of the current state of affairs and potential future developments in the diagnostic utility of PET in prostate cancer.

  4. Deciphering cancer heterogeneity: the biological space

    Directory of Open Access Journals (Sweden)

    Stephanie eRoessler

    2014-04-01

    Full Text Available Most lethal solid tumors including hepatocellular carcinoma (HCC are considered incurable due to extensive heterogeneity in clinical presentation and tumor biology. Tumor heterogeneity may result from different cells of origin, patient ethnicity, etiology, underlying disease and diversity of genomic and epigenomic changes which drive tumor development. Cancer genomic heterogeneity thereby impedes treatment options and poses a significant challenge to cancer management. Studies of the HCC genome have revealed that although various genomic signatures identified in different HCC subgroups share a common prognosis, each carries unique molecular changes which are linked to different sets of cancer hallmarks whose misregulation has been proposed by Hanahan and Weinberg to be essential for tumorigenesis. We hypothesize that these specific sets of cancer hallmarks collectively occupy different tumor biological space representing the misregulation of different biological processes. In principle, a combination of different cancer hallmarks can result in new convergent molecular networks that are unique to each tumor subgroup and represent ideal druggable targets. Due to the ability of the tumor to adapt to external factors such as treatment or changes in the tumor microenvironment, the tumor biological space is elastic. Our ability to identify distinct groups of cancer patients with similar tumor biology who are most likely to respond to a specific therapy would have a significant impact on improving patient outcome. It is currently a challenge to identify a particular hallmark or a newly emerged convergent molecular network for a particular tumor. Thus, it is anticipated that the integration of multiple levels of data such as genomic mutations, somatic copy number aberration, gene expression, proteomics, and metabolomics, may help us grasp the tumor biological space occupied by each individual, leading to improved therapeutic intervention and outcome.

  5. Measurement Frontiers in Molecular Biology

    Science.gov (United States)

    Laderman, Stephen

    2009-03-01

    Developments of molecular measurements and manipulations have long enabled forefront research in evolution, genetics, biological development and its dysfunction, and the impact of external factors on the behavior of cells. Measurement remains at the heart of exciting and challenging basic and applied problems in molecular and cell biology. Methods to precisely determine the identity and abundance of particular molecules amongst a complex mixture of similar and dissimilar types require the successful design and integration of multiple steps involving biochemical manipulations, separations, physical probing, and data processing. Accordingly, today's most powerful methods for characterizing life at the molecular level depend on coordinated advances in applied physics, biochemistry, chemistry, computer science, and engineering. This is well illustrated by recent approaches to the measurement of DNA, RNA, proteins, and intact cells. Such successes underlie well founded visions of how molecular biology can further assist in answering compelling scientific questions and in enabling the development of remarkable advances in human health. These visions, in turn, are motivating the interdisciplinary creation of even more comprehensive measurements. As a further and closely related consequence, they are motivating innovations in the conceptual and practical approaches to organizing and visualizing large, complex sets of interrelated experimental results and distilling from those data compelling, informative conclusions.

  6. Review of "Cancer Nanotechnology: Methods and Protocols (Methods in Molecular Biology" by Stephen R. Grobmyer (Editor, Brij M. Moudgil (Editor

    Directory of Open Access Journals (Sweden)

    Steinmetz Nicole F

    2010-09-01

    Full Text Available Abstract Cancer remains one of the leading causes of death. Research and resulting technologies have contributed to rising numbers of cancer survivors. Cancer nanotechnology is a novel and burgeoning field with the promise to open the door for the development of improved cancer therapies and detection methods. Cancer nanotechnology has the potential to become clinical reality.

  7. Systems biology: confronting the complexity of cancer.

    Science.gov (United States)

    Gentles, Andrew J; Gallahan, Daniel

    2011-09-15

    The AACR-NCI Conference "Systems Biology: Confronting the Complexity of Cancer" took place from February 27 to March 2, 2011, in San Diego, CA. Several themes resonated during the meeting, notably (i) the need for better methods to distill insights from large-scale networks, (ii) the importance of integrating multiple data types in constructing more realistic models, (iii) challenges in translating insights about tumorigenic mechanisms into therapeutic interventions, and (iv) the role of the tumor microenvironment, at the physical, cellular, and molecular levels. The meeting highlighted concrete applications of systems biology to cancer, and the value of collaboration between interdisciplinary researchers in attacking formidable problems.

  8. Molecular biology of Plasmodiophora brassicae

    DEFF Research Database (Denmark)

    Siemens, Johannes; Bulman, Simon; Rehn, Frank

    2009-01-01

    of several genes have been revealed, and the expression of those genes has been linked to development of clubroot to some extent. In addition, the sequence data have reinforced the inclusion of the plasmodiophorids within the Cercozoa. The recent successes in molecular biology have produced new approaches......Initially, molecular techniques were used to detect and distinguish Plasmodiophora pathotypes in soil. Meanwhile, chromosomes from 2.2 Mb to 680 kb are characterized and the total genome size is estimated to be approximately 20 Mb. Furthermore, the genomic gene structure and the cDNA structure...

  9. Advanced computational biology methods identify molecular switches for malignancy in an EGF mouse model of liver cancer.

    Directory of Open Access Journals (Sweden)

    Philip Stegmaier

    Full Text Available The molecular causes by which the epidermal growth factor receptor tyrosine kinase induces malignant transformation are largely unknown. To better understand EGFs' transforming capacity whole genome scans were applied to a transgenic mouse model of liver cancer and subjected to advanced methods of computational analysis to construct de novo gene regulatory networks based on a combination of sequence analysis and entrained graph-topological algorithms. Here we identified transcription factors, processes, key nodes and molecules to connect as yet unknown interacting partners at the level of protein-DNA interaction. Many of those could be confirmed by electromobility band shift assay at recognition sites of gene specific promoters and by western blotting of nuclear proteins. A novel cellular regulatory circuitry could therefore be proposed that connects cell cycle regulated genes with components of the EGF signaling pathway. Promoter analysis of differentially expressed genes suggested the majority of regulated transcription factors to display specificity to either the pre-tumor or the tumor state. Subsequent search for signal transduction key nodes upstream of the identified transcription factors and their targets suggested the insulin-like growth factor pathway to render the tumor cells independent of EGF receptor activity. Notably, expression of IGF2 in addition to many components of this pathway was highly upregulated in tumors. Together, we propose a switch in autocrine signaling to foster tumor growth that was initially triggered by EGF and demonstrate the knowledge gain form promoter analysis combined with upstream key node identification.

  10. Biological Therapies for Cancer

    Science.gov (United States)

    ... Medicine 2009;7:11. [PubMed Abstract] Pardoll D. Cancer immunology. In: Abeloff M, Armitage J, Niederhuber J, Kastan ... 363(5):411-422. [PubMed Abstract] Finn OJ. Cancer immunology. New England Journal of Medicine 2008;358(25): ...

  11. Marine molecular biology: an emerging field of biological sciences.

    Science.gov (United States)

    Thakur, Narsinh L; Jain, Roopesh; Natalio, Filipe; Hamer, Bojan; Thakur, Archana N; Müller, Werner E G

    2008-01-01

    An appreciation of the potential applications of molecular biology is of growing importance in many areas of life sciences, including marine biology. During the past two decades, the development of sophisticated molecular technologies and instruments for biomedical research has resulted in significant advances in the biological sciences. However, the value of molecular techniques for addressing problems in marine biology has only recently begun to be cherished. It has been proven that the exploitation of molecular biological techniques will allow difficult research questions about marine organisms and ocean processes to be addressed. Marine molecular biology is a discipline, which strives to define and solve the problems regarding the sustainable exploration of marine life for human health and welfare, through the cooperation between scientists working in marine biology, molecular biology, microbiology and chemistry disciplines. Several success stories of the applications of molecular techniques in the field of marine biology are guiding further research in this area. In this review different molecular techniques are discussed, which have application in marine microbiology, marine invertebrate biology, marine ecology, marine natural products, material sciences, fisheries, conservation and bio-invasion etc. In summary, if marine biologists and molecular biologists continue to work towards strong partnership during the next decade and recognize intellectual and technological advantages and benefits of such partnership, an exciting new frontier of marine molecular biology will emerge in the future.

  12. Systems biology in molecular psychiatry.

    Science.gov (United States)

    Gebicke-Haerter, P J

    2008-09-01

    The last ten to fifteen years have seen a remarkable shift of research strategies from hypothesis-driven, reductionistic to data driven, hypothesis-free approaches. This tendency has become evident after completion of the sequencing of the human genome, when publications under the label systems biology have been skyrocketing. This shift marks a gradual revision of scientific understanding of biological systems. Whilst the former has been component-oriented, precluding elements that do not belong to the hypothesis, the latter try to extract information from the whole system in the first place. Only with this information at hand, data driven strategies develop hypotheses. Data driven strategies unearth the immense complexity of biological systems and, hence, necessitate computer-aided support. Mathematical tools derived from chaos theory appear to be applicable in biological systems, but require significant improvements. The combination of high throughput data collection with in silico modelling of molecular or higher order systems can markedly extend our understanding of onset and progression of diseases. Undoubtedly, systems thinking in brain research is the greatest challenge for the years to come.

  13. Genetic and molecular changes in ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Robert L Hollis; Charlie Gourley

    2016-01-01

    Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.

  14. Structural Biology and Molecular Applications Research

    Science.gov (United States)

    Part of NCI's Division of Cancer Biology's research portfolio, research and development in this area focuses on enabling technologies, models, and methodologies to support basic and applied cancer research.

  15. Cold Spring Harbor symposia on quantitative biology: Volume 51, Molecular biology of /ital Homo sapiens/

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    This volume is the second part of a collection of papers submitted by the participants to the 1986 Cold Spring Harbor Symposium on Quantitative Biology entitled Molecular Biology of /ital Homo sapiens/. The 49 papers included in this volume are grouped by subject into receptors, human cancer genes, and gene therapy. (DT)

  16. Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

    Science.gov (United States)

    Gilad, Assaf A; Shapiro, Mikhail G

    2017-02-17

    Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

  17. 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.

  18. Molecular characteristics versus biological activity

    Science.gov (United States)

    Applegate, Vernon C.; Smith, Manning A.; Willeford, Bennett R.

    1967-01-01

    The molecular characteristics of mononitrophenols containing halogens not only play a key role in their biological activity but provide a novel example of selective toxicity among vertebrate animals. It has been reported that efforts to control the parasitic sea lamprey in the Great Lakes are directed at present to the applications of a selective toxicant to streams inhabited by lamprey larvae. Since 1961, the larvicide that has been used almost exclusively in the control program has been 3-trifluoromethyl-4-nitrophenol (TFM). However, this is only one of about 15 closely related compounds, all halogen-containing mononitrophenols, that display a selectively toxic action upon lampreys. Although not all of the halogenated mononitrophenols are selectively toxic to lampreys (in fact, fewer than half of those tested), no other group of related compounds has displayed any useful larvicidal activity except for the substituted nitrosalicylanilides.

  19. History of the molecular biology of cytomegaloviruses.

    Science.gov (United States)

    Stinski, Mark F

    2014-01-01

    The history of the molecular biology of cytomegaloviruses from the purification of the virus and the viral DNA to the cloning and expression of the viral genes is reviewed. A key genetic element of cytomegalovirus (the CMV promoter) contributed to our understanding of eukaryotic cell molecular biology and to the development of lifesaving therapeutic proteins. The study of the molecular biology of cytomegaloviruses also contributed to the development of antivirals to control the viral infection.

  20. 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.

  1. Laboratory of Cell and Molecular Biology

    Data.gov (United States)

    Federal Laboratory Consortium — The Laboratory of Cell and Molecular Biology investigates the organization, compartmentalization, and biochemistry of eukaryotic cells and the pathology associated...

  2. Development of Mouse Models of Ovarian Cancer for Studying Tumor Biology and Testing Novel Molecularly Targeted Therapeutic Strategies

    Science.gov (United States)

    2011-09-01

    mounting clinico -pathologic and molecular data have led Kurman and Shih to propose a new model in which OvCas are divided into 2 main categories—type I... cases from which data were prospectively collected more than a 20-year period at a single center, 48%were high stage at diagnosis and these were

  3. Molecular and genetic bases of pancreatic cancer.

    Science.gov (United States)

    Vaccaro, Vanja; Gelibter, Alain; Bria, Emilio; Iapicca, Pierluigi; Cappello, Paola; Di Modugno, Francesca; Pino, Maria Simona; Nuzzo, Carmen; Cognetti, Francesco; Novelli, Francesco; Nistico, Paola; Milella, Michele

    2012-06-01

    Pancreatic cancer remains a formidable challenge for oncologists and patients alike. Despite intensive efforts, attempts at improving survival in the past 15 years, particularly in advanced disease, have failed. This is true even with the introduction of molecularly targeted agents, chosen on the basis of their action on pathways that were supposedly important in pancreatic cancer development and progression: indeed, with the notable exception of the epidermal growth factor receptor (EGFR) inhibitor erlotinib, that has provided a minimal survival improvement when added to gemcitabine, other agents targeting EGFR, matrix metallo-proteases, farnesyl transferase, or vascular endothelial growth factor have not succeeded in improving outcomes over standard gemcitabine monotherapy for a variety of different reasons. However, recent developments in the molecular epidemiology of pancreatic cancer and an ever evolving understanding of the molecular mechanisms underlying pancreatic cancer initiation and progression raise renewed hope to find novel, relevant therapeutic targets that could be pursued in the clinical setting. In this review we focus on molecular epidemiology of pancreatic cancer, epithelial-to-mesenchymal transition and its influence on sensitivity to EGFR-targeted approaches, apoptotic pathways, hypoxia-related pathways, developmental pathways (such as the hedgehog and Notch pathways), and proteomic analysis as keys to a better understanding of pancreatic cancer biology and, most importantly, as a source of novel molecular targets to be exploited therapeutically.

  4. Bladder cancer: molecular determinants of personalized therapy.

    Science.gov (United States)

    Lopez-Beltran, Antonio; Santoni, Matteo; Massari, Francesco; Ciccarese, Chiara; Tortora, Giampaolo; Cheng, Liang; Moch, Holger; Scarpelli, Marina; Reymundo, Carlos; Montironi, Rodolfo

    2015-01-01

    Several molecular and genetic studies have provided new perspectives on the histologic classification of bladder tumors. Recent developments in the field of molecular mutational pathway analyses based on next generation sequencing technology together with classic data derived from the description of mutations in the FGFR3 (fibroblast growth factor receptor 3) gene, mutations on TP53 gene, and cDNA technology profiling data gives support to a differentiated taxonomy of bladder cancer. All these changes are behind the use of non-traditional approach to therapy of bladder cancer patients and are ready to change our daily practice of uro-oncology. The observed correlation of some molecular alterations with tumor behavior and the identification of their targets at cellular level might support the use of molecular changes together with morphological data to develop new clinical and biological strategies to manage patients with urothelial cancer. The current review provides comprehensive data to support personalized therapy for bladder cancer based on an integrated approach including pathologic and clinical features and molecular biology.

  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. Monod and the spirit of molecular biology.

    Science.gov (United States)

    Morange, Michel

    2015-06-01

    The founders of molecular biology shared views on the place of biology within science, as well as on the relations of molecular biology to Darwinism. Jacques Monod was no exception, but the study of his writings is particularly interesting because he expressed his point of view very clearly and pushed the implications of some of his choices further than most of his contemporaries. The spirit of molecular biology is no longer the same as in the 1960s but, interestingly, Monod anticipated some recent evolutions of this discipline.

  7. Biochemistry and Molecular Biology Education (BAMBED

    Directory of Open Access Journals (Sweden)

    Voet Donald

    2004-05-01

    Full Text Available Biochemistry and Molecular Biology Education (BAMBED is a journal that is a publication of the In-ternational Union of Biochemistry and Molecular Biology (IUBMB and is published by the AmericanSociety of Biochemistry and Molecular Biology (ASBMB. BAMBED, as its name indicates, publishesarticles of interest to educators in biochemistry and molecular biology. These include invited reviewson subjects not yet in textbooks, discussions of curricular development, new laboratory exercises,and articles on educational research. BAMBED also publishes Features on Problem-Based Learning(PBL, Biotechnology Education, and Multimedia in Biochemistry and Molecular Biology Educati-on. An important aspect of these articles is that their educational eectiveness must be assessed. Ishall discuss in greater detail the types of articles that BAMBED publishes and the criteria used foraccepting them for publication. Conference attendees are encouraged to submit articles to BAMBED.

  8. Molecular ferroelectrics: where electronics meet biology.

    Science.gov (United States)

    Li, Jiangyu; Liu, Yuanming; Zhang, Yanhang; Cai, Hong-Ling; Xiong, Ren-Gen

    2013-12-28

    In the last several years, we have witnessed significant advances in molecular ferroelectrics, with the ferroelectric properties of molecular crystals approaching those of barium titanate. In addition, ferroelectricity has been observed in biological systems, filling an important missing link in bioelectric phenomena. In this perspective, we will present short historical notes on ferroelectrics, followed by an overview of the fundamentals of ferroelectricity. The latest developments in molecular ferroelectrics and biological ferroelectricity will then be highlighted, and their implications and potential applications will be discussed. We close by noting molecular ferroelectric as an exciting frontier between electronics and biology, and a number of challenges ahead are also described.

  9. Origins of molecular biology in Japan.

    Science.gov (United States)

    Obayashi, M

    1986-06-01

    The purpose of this paper is to discuss the origins of molecular biology in Japan. Japanese molecular biology does not have a long history since it started only after World War II. Especially, molecular genetics which uses "bacteriophage" had hardly been studied before the war and only a few scientists were interested in it immediately after the war. This is one of the origins of molecular biology in Japan. But there are other origins, one of which is the group formed by biologists, biochemists and physicists interested in nucleic acids. This group also started just after the war. Still another origin is the group of enzymologists. Enzymology was one of the main subjects of biochemistry from before the war. In Japan, biochemistry developed in conjunction with the medical and agricultural sciences from the pre-war era. These played an important role in introducing molecular biology from Europe and the United States after the war. A historical study of the development of molecular biology in Japan, comparing it with the history of molecular biology in Europe and the United States, should contribute to the elucidation of the features of the history of molecular biology in Japan.

  10. Marine molecular biology: An emerging field of biological sciences

    Digital Repository Service at National Institute of Oceanography (India)

    Thakur, N.L.; Jain, R.; Natalio, F.; Hamer, B.; Thakur, A.N.; Muller, W.E.G.

    to tackle problems associated with global climate changes, bio- diversity, environmental quality and use of marine living re- sources (Molecular biology in marine science, 1994). Marine biologists study oceanic life in relation to marine environment... that often range from small to global scale, whereas, molecular biologist study biological events in terms of the physiochemical properties of molecules. The immediate benefits of the collab- orative research between these two disciplines could include...

  11. The Molecular Biology Capstone Assessment: A Concept Assessment for Upper-Division Molecular Biology Students

    Science.gov (United States)

    Couch, Brian A.; Wood, William B.; Knight, Jennifer K.

    2015-01-01

    Measuring students' conceptual understandings has become increasingly important to biology faculty members involved in evaluating and improving departmental programs. We developed the Molecular Biology Capstone Assessment (MBCA) to gauge comprehension of fundamental concepts in molecular and cell biology and the ability to apply these concepts in…

  12. Molecular diagnosis of prostate cancer: Topical issues

    Directory of Open Access Journals (Sweden)

    E. N. Knyazev

    2014-12-01

    Full Text Available Prostate cancer (PC is the second most common cancer and the fifth highest malignancy mortality rate in men worldwide. Although PC is detectable in 15-20% of men during life, its death risk is only about 3%. This means that not all PC cases require the same management tactics. The given review analyzes the current investigations searching for molecular biological markers to predict the course of PC and to choose its treatment policy, including that in the development of resistance to androgen-deprivation therapy.

  13. European Conference on Molecular Biology EMBO

    CERN Multimedia

    1967-01-01

    European Conference on Molecular Biology, which eventually led to the setting up of EMBO, was held at CERN in April. Olivier Reverdin is adressing the delegates. Bernard Gregory is on the left and Willy Spuhler in the centre.

  14. Application of molecular biology in exercise physiology.

    Science.gov (United States)

    Booth, F W

    1989-01-01

    Past progress in exercise biochemical research has often depended on the use of knowledge and techniques which were originally reported from other disciplines. With the advent of newer methodologies in molecular biology, the purpose of this review has been to document the status of information gained from the application of molecular biological techniques to questions in exercise physiology. Furthermore, this review has speculated how new methods in molecular biology might be employed to answer classic questions in exercise physiology. A powerful revolution in science, that is, molecular biology, will provide new information about exercise mechanisms, which ideally will improve the training programs for elite athletes as well as continue to be associated with the public's interest in exercise training.

  15. 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.

  16. Biological Significance and the Related Molecular Mechanism of Ets1 mRNA Expression in Lung Cancer by Tissue Microarray (TMA)

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the expressions and molecular mechanism of Ets-1 mRNA, and TGFβ1 and c-Met proteins in the pathogenesis, progression of lung cancer by tissue microarray (TMA) method. Methods: The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were detected in 89 primary lung cancers, 12 lung cancer with lymph-node metastasis and 12 precancerous lesions by FISH(fluorescence in situ hybridization) and immunohistochemical method, and 10 normal lung tissues were used as controls. Results: The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were significantly higher in 89 primary lung cancer than in the control group (P<0.05). The expressions of Ets-1 mRNA, and TGFβ1 and c-Met proteins were related to lymph node metastasis and clinical stages. There was a positive correlation between the Ets-1 mRNA expression and TGFβ1 and c-Met proteins (P<0.05). Conclusion: Ets-1 mRNA, TGFβ1 and c-Met proteins may be related to the pathogenesis, progression and malignant behavior of lung cancer. They may play an important role in prognosis assessment of lung cancer.

  17. Emerging molecular approaches in stem cell biology.

    Science.gov (United States)

    Jaishankar, Amritha; Vrana, Kent

    2009-04-01

    Stem cells are characterized by their ability to self-renew and differentiate into multiple adult cell types. Although substantial progress has been made over the last decade in understanding stem cell biology, recent technological advances in molecular and systems biology may hold the key to unraveling the mystery behind stem cell self-renewal and plasticity. The most notable of these advances is the ability to generate induced pluripotent cells from somatic cells. In this review, we discuss our current understanding of molecular similarities and differences among various stem cell types. Moreover, we survey the current state of systems biology and forecast future needs and direction in the stem cell field.

  18. Molecular imaging in cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Michalski, Mark H. [Stanford University School of Medicine, Stanford, CA (United States); Chen, Xiaoyuan [National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), National Institute of Biomedical Imaging and Bioengineering (NIBIB), Bethesda, MD (United States)

    2011-02-15

    The success of cancer therapy can be difficult to predict, as its efficacy is often predicated upon characteristics of the cancer, treatment, and individual that are not fully understood or are difficult to ascertain. Monitoring the response of disease to treatment is therefore essential and has traditionally been characterized by changes in tumor volume. However, in many instances, this singular measure is insufficient for predicting treatment effects on patient survival. Molecular imaging allows repeated in vivo measurement of many critical molecular features of neoplasm, such as metabolism, proliferation, angiogenesis, hypoxia, and apoptosis, which can be employed for monitoring therapeutic response. In this review, we examine the current methods for evaluating response to treatment and provide an overview of emerging PET molecular imaging methods that will help guide future cancer therapies. (orig.)

  19. Ovarian cancer: a molecularly insidious disease.

    Science.gov (United States)

    Mezzanzanica, Delia

    2015-01-01

    In this issue of the Chinese Journal of Cancer, European, American, and Chinese experts review the current management and future perspectives of epithelial ovarian cancer (EOC), the leading cause of gynecological cancer deaths. Although major advances have been made in understanding the cellular and molecular biology of this highly heterogeneous malignancy, the survival rate of women with EOC has changed little since the introduction of platinum-based treatment as a front-line therapy. The papers describe the progress in deciphering the molecular complexity of this disease and the newly available molecular-driven therapies, which have been applied by shifting trial designs toward restricting eligibility to specific subgroups of patients rather than testing agents in unselected populations. These new trial designs provide potential opportunities for improved efficacy in targeted populations. Given the molecular complexity of this disease, patient survival may be increased by searching for new molecular prognostic/predictive signatures as well as by translating the recent insight of microRNA involvement in EOC progression into new, targeted therapies. Particular attention has been given to the issue of fertility sparing for women affected by curable diseases.

  20. Cell and molecular biology of epidermal growth factor receptor.

    Science.gov (United States)

    Ceresa, Brian P; Peterson, Joanne L

    2014-01-01

    The epidermal growth factor receptor (EGFR) has been one of the most intensely studied cell surface receptors due to its well-established roles in developmental biology, tissue homeostasis, and cancer biology. The EGFR has been critical for creating paradigms for numerous aspects of cell biology, such as ligand binding, signal transduction, and membrane trafficking. Despite this history of discovery, there is a continual stream of evidence that only the surface has been scratched. New ways of receptor regulation continue to be identified, each of which is a potential molecular target for manipulating EGFR signaling and the resultant changes in cell and tissue biology. This chapter is an update on EGFR-mediated signaling, and describes some recent developments in the regulation of receptor biology.

  1. Molecular Taxonomy and Tumourigenesis of Colorectal Cancer.

    Science.gov (United States)

    Biswas, S; Holyoake, D; Maughan, T S

    2016-02-01

    Over the last 5 years there has been a surge in interest in the molecular classification of colorectal cancer. The effect of molecular subtyping on current treatment decisions is limited to avoidance of adjuvant 5-fluorouracil chemotherapy in stage II microsatellite unstable-high disease and avoidance of epidermal growth factor receptor-targeted antibodies in extended RAS mutant tumours. The emergence of specific novel combination therapy for the BRAF-mutant cohort and of the microsatellite unstable-high cohort as a responsive group to immune checkpoint inhibition shows the growing importance of a clinically relevant molecular taxonomy. Clinical trials such as the Medical Research Council FOCUS4 trial using biomarkers to select patients for specific therapies are currently open and testing such approaches. The integration of mutation, gene expression and pathological analyses is refining our understanding of the biological subtypes within colorectal cancer. Sharing of data sets of parallel sequencing and gene expression of thousands of cancers among independent groups has allowed the description of disease subsets and the need for a validated consensus classification has become apparent. This biological understanding of the disease is a key step forward in developing a stratified approach to patient management. The discovery of stratifiers that predict a response to existing and emerging therapies will enable better use of these treatments. Improved scientific understanding of the biological characteristics of poorly responsive subgroups will facilitate the design of novel biologically rational combinations. Novel treatment regimens, including the combination of new drugs with radiation, and the discovery and validation of their associated predictive biomarkers will gradually lead to improved outcomes from therapy.

  2. Using Molecular Biology to Develop Drugs for Renal Cell Carcinoma

    Science.gov (United States)

    Cowey, C. Lance; Rathmell, W. Kimryn

    2010-01-01

    Background Renal cell carcinoma is a disease marked by a unique biology which has governed it’s long history of poor response to conventional cancer treatments. The discovery of the signaling pathway activated as a result of inappropriate constitutive activation of the hypoxia inducible factors (HIF), transcription factors physiologically and transiently stabilized in response to low oxygen, has provided a primary opportunity to devise treatment strategies to target this oncogenic pathway. Objective A review of the molecular pathogenesis of renal cell cancer as well as molecularly targeted therapies, both those currently available and those in development, will be provided. In addition, trials involving combination or sequential targeted therapy are discussed. Methods A detailed review of the literature describing the molecular biology of renal cell cancer and novel therapies was performed and summarized. Results/Conclusion Therapeutics targeting angiogenesis have provided the first class of agents which provide clinical benefit in a large majority of patients and heralded renal cell carcinoma as a solid tumor paradigm for the development of novel therapeutics. Multiple strategies targeting this pathway and now other identified pathways in renal cell carcinoma provide numerous potential opportunities to make major improvements in treating this historically devastating cancer. PMID:20648240

  3. Molecular biological research on Foraminifera

    Institute of Scientific and Technical Information of China (English)

    LI Baohua; Kemal Topac ERTAN; Christoph HEMLEBEN

    2005-01-01

    As one of the most important groups in micropaleontology, Foraminifera is traditionally described to have a membranous, agglutinated or carbonate shell according to its morphology, which resembles the marine granuloreticuloseans. However, recent molecular analyses on its ribosomal RNA gene have disclosed the existence of the naked, and also freshwater and terrestrial species.Foraminiferal SSU rDNA sequence suggests that this group is positioned at the base of the Eukaryotes phylogenetic trees, between Euglenoida and Diplomonadida. Existence of a large amount of genetic types in planktonic foraminifera suggests an underestimation of the biodiversity for the nearly 50 species in world oceans and their close relationship with the ocean environment, such as bio-geographic distribution and water currents. This provides a more reliable proxy for future paleoenvironmental study.

  4. Frontiers of NMR in Molecular Biology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-08-25

    NMR spectroscopy is expanding the horizons of structural biology by determining the structures and describing the dynamics of blobular proteins in aqueous solution, as well as other classes of proteins including membrane proteins and the polypeptides that form the aggregates diagnostic of prion and amyloid diseases. Significant results are also emerging on DNA and RNA oligomers and their complexes with proteins. This meeting focused attention on key structural questions emanating from molecular biology and how NMR spectroscopy can be used to answer them.

  5. The Molecular Biology Database Collection: 2008 update.

    Science.gov (United States)

    Galperin, Michael Y

    2008-01-01

    The Nucleic Acids Research online Molecular Biology Database Collection is a public repository that lists more than 1000 databases described in this and previous Nucleic Acids Research annual database issues, as well as a selection of molecular biology databases described in other journals. All databases included in this Collection are freely available to the public. The 2008 update includes 1078 databases, 110 more than the previous one. The links to more than 80 databases have been updated and 25 obsolete databases have been removed from the list. The complete database list and summaries are available online at the Nucleic Acids Research web site, http://nar.oxfordjournals.org/.

  6. 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.

  7. Dictyostelium discoideum: Molecular approaches to cell biology

    Energy Technology Data Exchange (ETDEWEB)

    Spudich, J.A.

    1987-01-01

    The central point of this book is to present Dictyostelium as a valuable eukaryotic organism for those interested in molecular studies that require a combined biochemical, structural, and genetic approach. The book is not meant to be a comprehensive compilation of all methods involving Dictyostelium, but instead is a selective set of chapters that demonstrates the utility of the organism for molecular approaches to interesting cell biological problems.

  8. Molecular biology of Homo sapiens: Abstracts of papers presented at the 51st Cold Spring Harbor symposium on quantitative biology

    Energy Technology Data Exchange (ETDEWEB)

    Watson, J.D.; Siniscalco, M.

    1986-01-01

    This volume contains abstracts of papers presented at the 51st Cold Springs Harbor Symposium on Quantitative Biology. The topic for this meeting was the ''Molecular Biology of Homo sapiens.'' Sessions were entitled Human Gene Map, Human Cancer Genes, Genetic Diagnosis, Human Evolution, Drugs Made Off Human Genes, Receptors, and Gene Therapy. (DT)

  9. Molecular Testing for Gastrointestinal Cancer

    Science.gov (United States)

    Lee, Hye Seung; Kim, Woo Ho; Kwak, Yoonjin; Koh, Jiwon; Bae, Jeong Mo; Kim, Kyoung-Mee; Chang, Mee Soo; Han, Hye Seung; Kim, Joon Mee; Kim, Hwal Woong; Chang, Hee Kyung; Choi, Young Hee; Park, Ji Y.; Gu, Mi Jin; Lhee, Min Jin; Kim, Jung Yeon; Kim, Hee Sung; Cho, Mee-Yon

    2017-01-01

    With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians. PMID:28219002

  10. Molecular biology of the Chlamydia pneumoniae surface

    DEFF Research Database (Denmark)

    Christiansen, Gunna; Østergaard, Lars; Birkelund, Svend

    1997-01-01

    Chlamydia pneumoniaeis a fastidious microorganism with a characteristic biphasic lifecycle causing a variety of human respiratory tract infections. There is limited knowledge about the molecular biology of C. pneumoniae, and only a few genes have been sequenced. The structure of the chlamydial...

  11. Molecular biology of the honey bee

    DEFF Research Database (Denmark)

    Munk, Kathe

    While hoeneybees represent model organisms with complex social structures within populations, a comprehensive understanding of developmental regulation in relation to sexual development as well as cast determination still remains. Despite decades of research explanations on mechanistics underlyin...... and functional molecular biological techniques to advance current interpretations of heneybee development...

  12. Book review: Baculovirus Molecular Biology, Second Edition

    Science.gov (United States)

    The application of cell culture and molecular biology methodologies to the study of baculoviruses has resulted in an explosion of information on this group of insect pathogens. The quantity of the corresponding literature on baculoviruses has reached a level difficult for any one researcher to mast...

  13. [Molecular diagnostics of lung cancer].

    Science.gov (United States)

    Ryska, A; Dziadziuszko, R; Olszewski, W; Berzinec, P; Öz, B; Gottfried, M; Cufer, T; Samarzija, M; Plank, L; Ostoros, Gy; Tímár, J

    2015-09-01

    Development of the target therapies of lung cancer was a rapid process which fundamentally changed the pathological diagnosis as well. Furthermore, molecular pathology became essential part of the routine diagnostics of lung cancer. These changes generated several practical problems and in underdeveloped countries or in those with reimbursement problems have been combined with further challenges. The central and eastern region of Europe are characterized by similar problems in this respect which promoted the foundation of NSCLC Working Group to provide up to date protocols or guidelines. This present paper is a summary of the molecular pathology and target therapy guidelines written with the notion that it has to be upgraded continuously according to the development of the field.

  14. Understanding biological functions through molecular networks

    Institute of Scientific and Technical Information of China (English)

    Jing-Dong Jackie Han

    2008-01-01

    The completion of genome sequences and subsequent high-throughput mapping of molecular networks have allowed us to study biology from the network perspective. Experimental, statistical and mathematical modeling approaches have been employed to study the structure, function and dynamics of molecular networks, and begin to reveal important links of various network properties to the functions of the biological systems. In agreement with these functional links, evolutionary selection of a network is apparently based on the function, rather than directly on the structure of the network. Dynamic modularity is one of the prominent features of molecular networks. Taking advantage of such a feature may simplify network-based biological studies through construction of process-specific modular networks and provide functional and mechanistic insights linking genotypic variations to complex traits or diseases, which is likely to be a key approach in the next wave of understanding complex human diseases. With the development of ready-to-use network analysis and modeling tools the networks approaches will be infused into everyday biological research in the near future.

  15. Molecular neurodegeneration: basic biology and disease pathways.

    Science.gov (United States)

    Vassar, Robert; Zheng, Hui

    2014-09-23

    The field of neurodegeneration research has been advancing rapidly over the past few years, and has provided intriguing new insights into the normal physiological functions and pathogenic roles of a wide range of molecules associated with several devastating neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's disease, and Down syndrome. Recent developments have also facilitated initial efforts to translate preclinical discoveries toward novel therapeutic approaches and clinical trials in humans. These recent developments are reviewed in the current Review Series on "Molecular Neurodegeneration: Basic Biology and Disease Pathways" in a number of state-of-the-art manuscripts that cover themes presented at the Third International Conference on Molecular Neurodegeneration: "Basic biology and disease pathways" held in Cannes, France, September, 2013.

  16. Bioenergetics molecular biology, biochemistry, and pathology

    CERN Document Server

    Ozawa, Takayuki

    1990-01-01

    The emergence of the Biochemical Sciences is underlined by the FAOB symposium in Seoul and highlighted by this Satellite meeting on the "New Bioenergetics. " Classical mitochondrial electron transfer and energy coupling is now complemented by the emerging molecular biology of the respiratory chain which is studied hand in hand with the recognition of mitochondrial disease as a major and emerging study in the basic and clinical medical sciences. Thus, this symposium has achieved an important balance of the fundamental and applied aspects of bioenergetics in the modern setting of molecular biology and mitochondrial disease. At the same time, the symposium takes note not only of the emerging excellence of Biochemical Studies in the Orient and indeed in Korea itself, but also retrospectively enjoys the history of electron transport and energy conservation as represented by the triumvirate ofYagi, King and Slater. Many thanks are due Drs. Kim and Ozawa for their elegant organization of this meeting and its juxtapo...

  17. Imaging cellular and molecular biological functions

    Energy Technology Data Exchange (ETDEWEB)

    Shorte, S.L. [Institut Pasteur, 75 - Paris (France). Plateforme d' Imagerie Dynamique PFID-Imagopole; Frischknecht, F. (eds.) [Heidelberg Univ. Medical School (Germany). Dept. of Parasitology

    2007-07-01

    'Imaging cellular and molecular biological function' provides a unique selection of essays by leading experts, aiming at scientist and student alike who are interested in all aspects of modern imaging, from its application and up-scaling to its development. Indeed the philosophy of this volume is to provide student, researcher, PI, professional or provost the means to enter this applications field with confidence, and to construct the means to answer their own specific questions. (orig.)

  18. 2004 Reversible Associations in Structure & Molecular Biology

    Energy Technology Data Exchange (ETDEWEB)

    Edward Eisenstein Nancy Ryan Gray

    2005-03-23

    The Gordon Research Conference (GRC) on 2004 Gordon Research Conference on Reversible Associations in Structure & Molecular Biology was held at Four Points Sheraton, CA, 1/25-30/2004. The Conference was well attended with 82 participants (attendees list attached). The attendees represented the spectrum of endeavor in this field coming from academia, industry, and government laboratories, both U.S. and foreign scientists, senior researchers, young investigators, and students.

  19. Discovering the intelligence in molecular biology.

    Science.gov (United States)

    Uberbacher, E

    1995-12-01

    The Third International Conference on Intelligent Systems in Molecular Biology was truly an outstanding event. Computational methods in molecular biology have reached a new level of maturity and utility, resulting in many high-impact applications. The success of this meeting bodes well for the rapid and continuing development of computational methods, intelligent systems and information-based approaches for the biosciences. The basic technology, originally most often applied to 'feasibility' problems, is now dealing effectively with the most difficult real-world problems. Significant progress has been made in understanding protein-structure information, structural classification, and how functional information and the relevant features of active-site geometry can be gleaned from structures by automated computational approaches. The value and limits of homology-based methods, and the ability to classify proteins by structure in the absence of homology, have reached a new level of sophistication. New methods for covariation analysis in the folding of large structures such as RNAs have shown remarkably good results, indicating the long-term potential to understand very complicated molecules and multimolecular complexes using computational means. Novel methods, such as HMMs, context-free grammars and the uses of mutual information theory, have taken center stage as highly valuable tools in our quest to represent and characterize biological information. A focus on creative uses of intelligent systems technologies and the trend toward biological application will undoubtedly continue and grow at the 1996 ISMB meeting in St Louis.

  20. 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.

  1. Can molecular cell biology explain chromosome motions?

    Directory of Open Access Journals (Sweden)

    Gagliardi L

    2011-05-01

    Full Text Available Abstract Background Mitotic chromosome motions have recently been correlated with electrostatic forces, but a lingering "molecular cell biology" paradigm persists, proposing binding and release proteins or molecular geometries for force generation. Results Pole-facing kinetochore plates manifest positive charges and interact with negatively charged microtubule ends providing the motive force for poleward chromosome motions by classical electrostatics. This conceptual scheme explains dynamic tracking/coupling of kinetochores to microtubules and the simultaneous depolymerization of kinetochore microtubules as poleward force is generated. Conclusion We question here why cells would prefer complex molecular mechanisms to move chromosomes when direct electrostatic interactions between known bound charge distributions can accomplish the same task much more simply.

  2. Lung cancer: Biology and treatment options.

    Science.gov (United States)

    Lemjabbar-Alaoui, Hassan; Hassan, Omer Ui; Yang, Yi-Wei; Buchanan, Petra

    2015-12-01

    Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLCs) and non-small cell lung carcinomas (NSCLCs). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation.

  3. 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.

  4. Molecular biology and its applications in orthodontics and oral and maxillofacial surgery

    Institute of Scientific and Technical Information of China (English)

    REN Yi-jin

    2005-01-01

    Molecular biology is an exciting, rapidly expanding field, which has enabled enormously greater understanding of the biology of diseases and malfunctions in many fields. It chiefly concerns itself with understanding the interactions between the various systems of a cell, including the interrelationship of DNA, RNA and protein synthesis and how these interactions are regulated. Since the introduction of molecular biology into modern science, numerous other fields have been enabled to go "molecular". Advanced molecular biological techniques showed us new avenue towards finding answers to the questions asked for decades. The first part of this article described the history of molecular biology.It started as a joined discipline of other areas of biology, i.e. genetics and biochemistry in the 1930s and 1940s, and enjoyed its classical period and became institutionalized in the 1950s and 1960s. Major molecular techniques manipulating proteins, DNA and RNA were introduced and their mechanisms were concisely illustrated. The current knowledge of molecular biology and their applications in orthodontic and oral and maxillofacial surgery, i.e. osteoclast differentiation and function, regulation of tooth movement, mechanotransduction/cell-signalling, bone fracture healing, oral cancer as well as craniofacial/dental anomalies and distraction osteogenesis were discussed. Although the problems of introducing molecular technologies are still substantial, it is anticipated that the future of medicine/dentistry will be "molecular": molecular prevention, molecular diagnosis and molecular therapy.

  5. The molecular biology of vertebrate olfaction.

    Science.gov (United States)

    Hayden, Sara; Teeling, Emma C

    2014-11-01

    The importance of chemosensation for vertebrates is reflected in the vast and variable nature of their chemosensory tissues, neurons, and genes, which we explore in this review. Immense progress has been made in elucidating the molecular biology of olfaction since the discovery of the olfactory receptor genes by Buck and Axel, which eventually won the authors the Nobel Prize. In particular, research linking odor ligands to olfactory receptors (ORs) is truly revolutionizing our understanding of how a large but limited number of chemosensory receptors can allow us to perceive the massive diversity of odors in our habitat. This research is providing insight into the evolution of genomes and providing the raw data needed to explore links between genotype and phenotype, still a grand challenge in biology. Research into olfaction is still developing and will no doubt continue until we have a clear understanding of how all odors are detected and the evolutionary forces that have molded the chemosensory subgenome in vertebrates. This knowledge will not only be a huge step in elucidating olfactory function, advancing scientific knowledge and techniques, but there are also commercial applications for this research. This review focuses on the molecular basis of chemosensation, particularly olfaction, its evolution across vertebrates and the recent molecular advances linking odors to their cognate receptors.

  6. Cancer and molecular biomarkers of phase 2

    DEFF Research Database (Denmark)

    Dalhoff, Kim; Enghusen Poulsen, Henrik

    2005-01-01

    as molecular genetic biomarkers of risk. GSTM(my)1 has been associated with an increased risk of colorectal cancer, lung cancer, and bladder cancer and GSTP(pi)1 with prostate cancer. UGT1A1*28 and *37 are both associated with an increased risk of breast cancer as is SULT1A1*2. The presence of UGT1A1...

  7. 2011 Archaea: Ecology, Metabolism, & Molecular Biology

    Energy Technology Data Exchange (ETDEWEB)

    Keneth Stedman

    2011-08-05

    Archaea, one of three major evolutionary lineages of life, are a fascinating and diverse group of microbes with deep roots overlapping those of eukaryotes. The focus of the 'Archaea: Ecology Metabolism & Molecular Biology' GRC conference expands on a number of emerging topics highlighting new paradigms in archaeal metabolism, genome function and systems biology; information processing; evolution and the tree of life; the ecology and diversity of archaea and their viruses. The strength of this conference lies in its ability to couple a field with a rich history in high quality research with new scientific findings in an atmosphere of stimulating exchange. This conference remains an excellent opportunity for younger scientists to interact with world experts in this field.

  8. 2009 Archaea: Ecology, Metabolism & Molecular Biology GRC

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Julie Maupin- Furlow

    2009-07-26

    Archaea, one of three major evolutionary lineages of life, are a fascinating and diverse group of microbes with deep roots overlapping those of eukaryotes. The focus of the 'Archaea: Ecology Metabolism & Molecular Biology' GRC conference expands on a number of emerging topics highlighting new paradigms in archaeal metabolism, genome function and systems biology; information processing; evolution and the tree of life; the ecology and diversity of archaea and their viruses; and industrial applications. The strength of this conference lies in its ability to couple a field with a rich history in high quality research with new scientific findings in an atmosphere of stimulating exchange. This conference remains an excellent opportunity for younger scientists to interact with world experts in this field.

  9. Archaea: Evolution, Physiology, and Molecular Biology

    DEFF Research Database (Denmark)

    Introduced by Crafoord Prize winner Carl Woese, this volume combines reviews of the major developments in archaeal research over the past 10-15 years with more specialized articles dealing with important recent breakthroughs. Drawing on major themes presented at the June 2005 meeting held in Muni...... and technological context, and include accounts of cutting-edge research developments. The book spans archaeal evolution, physiology, and molecular and cellular biology and will be an essential reference for both graduate students and researchers....... to honor the archaea pioneers Wolfram Zillig and Karl O. Stetter, the book provides a thorough survey of the field from its controversial beginnings to its ongoing expansion to include aspects of eukaryotic biology. The editors have assembled articles from the premier researchers in this rapidly burgeoning...

  10. Molecular Biological Methods in Environmental Engineering.

    Science.gov (United States)

    Zhang, Guocai; Wei, Li; Chang, Chein-Chi; Zhang, Yuhua; Wei, Dong

    2016-10-01

    Bacteria, acting as catalysts, perform the function of degrading pollutants. Molecular biological techniques play an important role in research on the community analysis, the composition and the functions of complex microbial communities. The development of secondary high-throughput pyrosequencing techiniques enhances the understanding of the composition of the microbial community. The literatures of 2015 indicated that 16S rDNA gene as genetic tag is still the important method for bacteria identification and classification. 454 high throughput sequencing and Illumina MiSeq sequencing have been the primary and widely recognized methods to analyze the microbial. This review will provide environmental engineers and microbiologists an overview of important advancements in molecular techniques and highlight the application of these methods in diverse environments.

  11. Genetics and molecular biology of hypotension

    Science.gov (United States)

    Robertson, D.

    1994-01-01

    Major strides in the molecular biology of essential hypertension are currently underway. This has tended to obscure the fact that a number of inherited disorders associated with low blood pressure exist and that these diseases may have milder and underrecognized phenotypes that contribute importantly to blood pressure variation in the general population. This review highlights some of the gene products that, if abnormal, could cause hypotension in some individuals. Diseases due to abnormalities in the catecholamine enzymes are discussed in detail. It is likely that genetic abnormalities with hypotensive phenotypes will be as interesting and diverse as those that give rise to hypertensive disorders.

  12. 2007 Archaea: Ecology, Metabolism and Molecular Biology

    Energy Technology Data Exchange (ETDEWEB)

    Imke Schroeder

    2008-09-18

    The Archaea are a fascinating and diverse group of prokaryotic organisms with deep roots overlapping those of eukaryotes. The focus of this GRC conference, 'Archaea: Ecology Metabolism & Molecular Biology', expands on a number of emerging topics highlighting the evolution and composition of microbial communities and novel archaeal species, their impact on the environment, archaeal metabolism, and research that stems from sequence analysis of archaeal genomes. The strength of this conference lies in its ability to couple reputable areas with new scientific topics in an atmosphere of stimulating exchange. This conference remains an excellent opportunity for younger scientists to interact with world experts in this field.

  13. Molecular markers as therapeutic targets in lung cancer

    Institute of Scientific and Technical Information of China (English)

    Hsin-Hui Tseng; Biao He

    2013-01-01

    Lung cancer is responsible for 29% of cancer deaths in the United States and has very low 5-year survival rates of approximately 11% in men and 15% in women.Although the early diagnosis of lung cancer may increase the survival rate with adequate treatment,advanced lung cancers are often metastasized and receive limited benefit from therapeutic regimens.As conventional treatments for lung cancer reach their limitations,researchers have attempted to discover novel drug therapies aimed at specific targets contributing to the progression of tumorigenesis.Recent advances in systems biology have enabled the molecular biology of lung carcinogenesis to be elucidated.Our understanding of the physiologic processes of tumor development provide a means to design more effective and specific drugs with less toxicity,thereby accelerating the delivery of new drug therapies to the patient's bedside.

  14. Molecular aspects of carcinogenesis in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Alexandros Koliopanos; Constantinos Avgerinos; Constantina Paraskeva; Zisis Touloumis; Dionisisa Kelgiorgi; Christos Dervenis

    2008-01-01

    BACKGROUND: Pancreatic cancer (PCa) is one of the most aggressive human solid tumors, with rapid growth and metastatic spread as well as resistance to chemotherapeutic drugs, leading rapidly to virtually incurable disease. Over the last 20 years, however, signiifcant advances have been made in our understanding of the molecular biology of PCa, with a focus on the cytogenetic abnormalities in PCa cell growth and differentiation. DATA SOURCES: A MEDLINE search and manual cross-referencing were utilized to identify published data for PCa molecular biology studies between 1986 and 2008, with emphasis on genetic alterations and developmental oncology. RESULTS: Activation of oncogenes, deregulation of tumor suppressor and genome maintenance genes, upregulation of growth factors/growth factor receptor signaling cascade systems, and alterations in cytokine expression, have been reported to play important roles in the process of pancreatic carcinogenesis. Alterations in the K-ras proto-oncogene and the p16INK4a, p53, FHIT, and DPC4 tumor suppressor genes occur in a high percentage of tumors. Furthermore, a variety of growth factors are expressed at increased levels. In addition, PCa often exhibits alterations in growth inhibitory pathways and evades apoptosis through p53 mutations and aberrant expression of apoptosis-regulating genes, such as members of the Bcl family. Additional pathways in the development of an aggressive phenotype, local inifltration and metastasis are still under ongoing genetic research. The present paper reviews recent studies on the pathogenesis of PCa, and includes a brief reference to alterations reported for other types of pancreatic tumor. CONCLUSIONS: Advances in molecular genetics and biology have improved our perception of the pathogenesis of PCa. However, further studies are needed to better understand the fundamental changes that occur in PCa, thus leading to better diagnostic and therapeutic management.

  15. Spherical Cancer Models in Tumor Biology

    Directory of Open Access Journals (Sweden)

    Louis-Bastien Weiswald

    2015-01-01

    Full Text Available Three-dimensional (3D in vitro models have been used in cancer research as an intermediate model between in vitro cancer cell line cultures and in vivo tumor. Spherical cancer models represent major 3D in vitro models that have been described over the past 4 decades. These models have gained popularity in cancer stem cell research using tumorospheres. Thus, it is crucial to define and clarify the different spherical cancer models thus far described. Here, we focus on in vitro multicellular spheres used in cancer research. All these spherelike structures are characterized by their well-rounded shape, the presence of cancer cells, and their capacity to be maintained as free-floating cultures. We propose a rational classification of the four most commonly used spherical cancer models in cancer research based on culture methods for obtaining them and on subsequent differences in sphere biology: the multicellular tumor spheroid model, first described in the early 70s and obtained by culture of cancer cell lines under nonadherent conditions; tumorospheres, a model of cancer stem cell expansion established in a serum-free medium supplemented with growth factors; tissue-derived tumor spheres and organotypic multicellular spheroids, obtained by tumor tissue mechanical dissociation and cutting. In addition, we describe their applications to and interest in cancer research; in particular, we describe their contribution to chemoresistance, radioresistance, tumorigenicity, and invasion and migration studies. Although these models share a common 3D conformation, each displays its own intrinsic properties. Therefore, the most relevant spherical cancer model must be carefully selected, as a function of the study aim and cancer type.

  16. 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.

  17. 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.

  18. Targeted therapies in epithelial ovarian cancer: Molecular mechanisms of action

    Institute of Scientific and Technical Information of China (English)

    Hiroaki; Itamochi

    2010-01-01

    Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage and have a poor prognosis.Currently, surgical tumor debulking, followed by platinum- and taxane-based chemotherapy is the standard treatment for advanced ovarian cancer. However, these patients are at great risk of recurrence and emerging drug resistance. Therefore, novel treatment strategies are required to improve outcomes for women with advanced ovarian cancer. A variety of molecular targeted agents, the majority of which are monoclonal antibodies and small-molecule protein-kinase inhibitors, have been explored in the management of ovarian cancer. The targets of these agents include angiogenesis, the human epidermal growth factor receptor family, ubiquitinproteasome pathway, epigenetic modulators, poly(ADPribose) polymerase (PARP), and mammalian target of rapamycin (mTOR) signaling pathway, which are aberrant in tumor tissue. The antiangiogenic agent, bevacizumab, has been reported as the most effective targeted agent and should be included in the standard chemotherapeutic regimen for advanced ovarian cancer. PARP inhibitors, which are mainly used in breast and ovarian cancer susceptibility gene-mutated patients, and mTOR inhibitors are also attractive treatment strategies, either alone or combination with chemotherapy, for ovarian cancer. Understanding the tumor molecular biology and identification of predictive biomarkers are essential steps for selection of the best treatment strategies. This article reviews the molecular mechanisms of the most promising targeted agents that are under early phase clinical evaluation for ovarian cancer.

  19. 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.

  20. 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.

  1. Molecular biology approaches in bioadhesion research

    Directory of Open Access Journals (Sweden)

    Marcelo Rodrigues

    2014-07-01

    Full Text Available The use of molecular biology tools in the field of bioadhesion is still in its infancy. For new research groups who are considering taking a molecular approach, the techniques presented here are essential to unravelling the sequence of a gene, its expression and its biological function. Here we provide an outline for addressing adhesion-related genes in diverse organisms. We show how to gradually narrow down the number of candidate transcripts that are involved in adhesion by (1 generating a transcriptome and a differentially expressed cDNA list enriched for adhesion-related transcripts, (2 setting up a BLAST search facility, (3 perform an in situ hybridization screen, and (4 functional analyses of selected genes by using RNA interference knock-down. Furthermore, latest developments in genome-editing are presented as new tools to study gene function. By using this iterative multi-technologies approach, the identification, isolation, expression and function of adhesion-related genes can be studied in most organisms. These tools will improve our understanding of the diversity of molecules used for adhesion in different organisms and these findings will help to develop innovative bio-inspired adhesives.

  2. Rhabdomyosarcoma: Advances in Molecular and Cellular Biology

    Directory of Open Access Journals (Sweden)

    Xin Sun

    2015-01-01

    Full Text Available Rhabdomyosarcoma (RMS is the most common soft tissue malignancy in childhood and adolescence. The two major histological subtypes of RMS are alveolar RMS, driven by the fusion protein PAX3-FKHR or PAX7-FKHR, and embryonic RMS, which is usually genetically heterogeneous. The prognosis of RMS has improved in the past several decades due to multidisciplinary care. However, in recent years, the treatment of patients with metastatic or refractory RMS has reached a plateau. Thus, to improve the survival rate of RMS patients and their overall well-being, further understanding of the molecular and cellular biology of RMS and identification of novel therapeutic targets are imperative. In this review, we describe the most recent discoveries in the molecular and cellular biology of RMS, including alterations in oncogenic pathways, miRNA (miR, in vivo models, stem cells, and important signal transduction cascades implicated in the development and progression of RMS. Furthermore, we discuss novel potential targeted therapies that may improve the current treatment of RMS.

  3. Molecular Imaging of Breast Cancer: Role of RGD Peptides.

    Science.gov (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Dash, Ashutosh

    2015-01-01

    Breast cancer is the leading cause of cancer deaths among women of all ages worldwide. With advances in molecular imaging procedures, it has been possible to detect breast cancer in its early stage, determine the extent of the disease to administer appropriate therapeutic protocol and also monitor the effects of treatment. By accurately characterizing the tumor properties and biological processes involved, molecular imaging can play a crucial role in minimizing the morbidity and mortality associated with breast cancer. The integrin αvβ3 plays an important role in breast cancer angiogenesis and is expressed on tumor endothelial cells as well as on some tumor cells. It is a receptor for the extracellular matrix proteins with the exposed arginine-glycine-aspartic acid (RGD) tripeptide sequence and therefore RGD peptides can preferentially bind to integrin αvβ3. In this context, targeting tumor vasculature or tumor cells by RGD-based probes is a promising strategy for molecular imaging of breast cancer. Using RGD-based probes, several preclinical studies have employed different imaging modalities such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound and optical imaging for visualization of integrin αvβ3 expression in breast cancer models. Limited clinical trials using (18)F-labeled RGD peptides have also been initiated for non-invasive detection and staging of breast cancer. Herein, we provide a comprehensive overview of the latest advances in molecular imaging of breast cancer using RGD peptide-based probes and discuss the challenges and opportunities for advancement of the field. The reported strategies for molecular imaging of breast cancer using RGD peptide-based probes holds promise for making clinically translatable advances that can positively impact the overall diagnostic and therapeutic processes and result in improved quality of life for breast cancer patients.

  4. Molecular Diagnostic Applications in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Laura Huth

    2014-06-01

    Full Text Available Colorectal cancer, a clinically diverse disease, is a leading cause of cancer-related death worldwide. Application of novel molecular diagnostic tests, which are summarized in this article, may lead to an improved survival of colorectal cancer patients.  Distinction of these applications is based on the different molecular principles found in colorectal cancer (CRC. Strategies for molecular analysis of single genes (as KRAS or TP53 as well as microarray based techniques are discussed. Moreover, in addition to the fecal occult blood testing (FOBT and colonoscopy some novel assays offer approaches for early detection of colorectal cancer like the multitarget stool DNA test or the blood-based Septin 9 DNA methylation test. Liquid biopsy analysis may also exhibit great diagnostic potential in CRC for monitoring developing resistance to treatment. These new diagnostic tools and the definition of molecular biomarkers in CRC will improve early detection and targeted therapy of colorectal cancer.

  5. 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.

  6. 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.

  7. Ins and outs of systems biology vis-à-vis molecular biology: continuation or clear cut?

    Science.gov (United States)

    De Backer, Philippe; De Waele, Danny; Van Speybroeck, Linda

    2010-03-01

    The comprehension of living organisms in all their complexity poses a major challenge to the biological sciences. Recently, systems biology has been proposed as a new candidate in the development of such a comprehension. The main objective of this paper is to address what systems biology is and how it is practised. To this end, the basic tools of a systems biological approach are explored and illustrated. In addition, it is questioned whether systems biology 'revolutionizes' molecular biology and 'transcends' its assumed reductionism. The strength of this claim appears to depend on how molecular and systems biology are characterised and on how reductionism is interpreted. Doing credit to molecular biology and to methodological reductionism, it is argued that the distinction between molecular and systems biology is gradual rather than sharp. As such, the classical challenge in biology to manage, interpret and integrate biological data into functional wholes is further intensified by systems biology's use of modelling and bioinformatics, and by its scale enlargement.

  8. The molecular biology capstone assessment: a concept assessment for upper-division molecular biology students.

    Science.gov (United States)

    Couch, Brian A; Wood, William B; Knight, Jennifer K

    2015-03-02

    Measuring students' conceptual understandings has become increasingly important to biology faculty members involved in evaluating and improving departmental programs. We developed the Molecular Biology Capstone Assessment (MBCA) to gauge comprehension of fundamental concepts in molecular and cell biology and the ability to apply these concepts in novel scenarios. Targeted at graduating students, the MBCA consists of 18 multiple-true/false (T/F) questions. Each question consists of a narrative stem followed by four T/F statements, which allows a more detailed assessment of student understanding than the traditional multiple-choice format. Questions were iteratively developed with extensive faculty and student feedback, including validation through faculty reviews and response validation through student interviews. The final assessment was taken online by 504 students in upper-division courses at seven institutions. Data from this administration indicate that the MBCA has acceptable levels of internal reliability (α=0.80) and test-retest stability (r=0.93). Students achieved a wide range of scores with a 67% overall average. Performance results suggest that students have an incomplete understanding of many molecular biology concepts and continue to hold incorrect conceptions previously documented among introductory-level students. By pinpointing areas of conceptual difficulty, the MBCA can provide faculty members with guidance for improving undergraduate biology programs.

  9. Molecular therapeutics in pancreas cancer

    Institute of Scientific and Technical Information of China (English)

    Vignesh Narayanan; Colin D Weekes

    2016-01-01

    The emergence of the "precision-medicine" paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma(PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease.

  10. A National Comparison of Biochemistry and Molecular Biology Capstone Experiences

    Science.gov (United States)

    Aguanno, Ann; Mertz, Pamela; Martin, Debra; Bell, Ellis

    2015-01-01

    Recognizing the increasingly integrative nature of the molecular life sciences, the "American Society for Biochemistry and Molecular Biology" (ASBMB) recommends that Biochemistry and Molecular Biology (BMB) programs develop curricula based on concepts, content, topics, and expected student outcomes, rather than courses. To that end,…

  11. Molecular biological aspects of acquired bullous diseases

    DEFF Research Database (Denmark)

    Dabelsteen, Erik

    1998-01-01

    Bullous diseases of the oral mucosa and skin were originally classified on the basis of clinical and histological criteria. The discovery of autoantibodies in some of these patients and the introduction of molecular biology have resulted in a new understanding of the pathological mechanisms of many...... of the bullous lesions. In this article, updated topics of the immune-mediated bullous lesions which involve oral mucosa and skin are reviewed. Pemphigus antigens, which are desmosomal-associated proteins and belong to the cadherin superfamily of cell adhesion proteins, have been isolated, and their genes have...... to be the target for mutations seen in patients with the inherited type of epidermolysis bullosa in which bullous lesions are a prominent clinical feature....

  12. 2010 Plant Molecular Biology Gordon Research Conference

    Energy Technology Data Exchange (ETDEWEB)

    Michael Sussman

    2010-07-23

    The Plant Molecular Biology Conference has traditionally covered a breadth of exciting topics and the 2010 conference will continue in that tradition. Emerging concerns about food security have inspired a program with three main themes: (1) genomics, natural variation and breeding to understand adaptation and crop improvement, (2) hormonal cross talk, and (3) plant/microbe interactions. There are also sessions on epigenetics and proteomics/metabolomics. Thus this conference will bring together a range of disciplines, will foster the exchange of ideas and enable participants to learn of the latest developments and ideas in diverse areas of plant biology. The conference provides an excellent opportunity for individuals to discuss their research because additional speakers in each session will be selected from submitted abstracts. There will also be a poster session each day for a two-hour period prior to dinner. In particular, this conference plays a key role in enabling students and postdocs (the next generation of research leaders) to mingle with pioneers in multiple areas of plant science.

  13. Biological (molecular and cellular) markers of toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Shugart, L.R.

    1990-10-01

    The overall objective of this study is to evaluate the use of the small aquarium fish, Japanese Medaka (Oryzias latipes), as a predictor of potential genotoxicity following exposure to carcinogens. This will be accomplished by quantitatively investigating the early molecular events associated with genotoxicity of various tissues of Medaka subsequent to exposure of the organism to several known carcinogens, such as diethylnitrosamine (DEN) and benzo(a)pyrene (BaP). Because of the often long latent period between initial contact with certain chemical and physical agents in our environment and subsequent expression of deleterious health or ecological impact, the development of sensitive methods for detecting and estimating early exposure is needed so that necessary interventions can ensue. A promising biological endpoint for detecting early exposure to damaging chemicals is the interaction of these compounds with cellular macromolecules such as Deoxyribonucleic acids (DNA). This biological endpoint assumes significance because it can be one of the critical early events leading eventually to adverse effects (neoplasia) in the exposed organism.

  14. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    Science.gov (United States)

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  15. Tea polyphenols, their biological effects and potential molecular targets.

    Science.gov (United States)

    Chen, D; Milacic, V; Chen, M S; Wan, S B; Lam, W H; Huo, C; Landis-Piwowar, K R; Cui, Q C; Wali, A; Chan, T H; Dou, Q P

    2008-04-01

    Tea is the most popular beverage in the world, second only to water. Tea contains an infusion of the leaves from the Camellia sinensis plant rich in polyphenolic compounds known as catechins, the most abundant of which is (-)-EGCG. Although tea has been consumed for centuries, it has only recently been studied extensively as a health-promoting beverage that may act to prevent a number of chronic diseases and cancers. The results of several investigations indicate that green tea consumption may be of modest benefit in reducing the plasma concentration of cholesterol and preventing atherosclerosis. Additionally, the cancer-preventive effects of green tea are widely supported by results from epidemiological, cell culture, animal and clinical studies. In vitro cell culture studies show that tea polyphenols potently induce apoptotic cell death and cell cycle arrest in tumor cells but not in their normal cell counterparts. Green tea polyphenols were shown to affect several biological pathways, including growth factor-mediated pathway, the mitogen-activated protein (MAP) kinase-dependent pathway, and ubiquitin/proteasome degradation pathways. Various animal studies have revealed that treatment with green tea inhibits tumor incidence and multiplicity in different organ sites such as skin, lung, liver, stomach, mammary gland and colon. Recently, phase I and II clinical trials have been conducted to explore the anticancer effects of green tea in humans. A major challenge of cancer prevention is to integrate new molecular findings into clinical practice. Therefore, identification of more molecular targets and biomarkers for tea polyphenols is essential for improving the design of green tea trials and will greatly assist in a better understanding of the mechanisms underlying its anti-cancer activity.

  16. Third international congress of plant molecular biology: Molecular biology of plant growth and development

    Energy Technology Data Exchange (ETDEWEB)

    Hallick, R.B. [ed.

    1995-02-01

    The Congress was held October 6-11, 1991 in Tucson with approximately 3000 scientists attending and over 300 oral presentations and 1800 posters. Plant molecular biology is one of the most rapidly developing areas of the biological sciences. Recent advances in the ability to isolate genes, to study their expression, and to create transgenic plants have had a major impact on our understanding of the many fundamental plant processes. In addition, new approaches have been created to improve plants for agricultural purposes. This is a book of presentation and posters from the conference.

  17. Biological stoichiometry in human cancer.

    Directory of Open Access Journals (Sweden)

    James J Elser

    Full Text Available BACKGROUND: A growing tumor in the body can be considered a complex ecological and evolutionary system. A new eco-evolutionary hypothesis (the "Growth Rate Hypothesis", GRH proposes that tumors have elevated phosphorus (P demands due to increased allocation to P-rich nucleic acids, especially ribosomal RNA, to meet the protein synthesis demands of accelerated proliferation. METHODOLOGY/PRINCIPAL FINDINGS: We determined the elemental (C, N, P and nucleic acid contents of paired malignant and normal tissues from colon, lung, liver, or kidney for 121 patients. Consistent with the GRH, lung and colon tumors were significantly higher (by approximately two-fold in P content (fraction of dry weight and RNA content and lower in nitrogen (N:P ratio than paired normal tissue, and P in RNA contributed a significantly larger fraction of total biomass P in malignant relative to normal tissues. Furthermore, patient-specific differences for %P between malignant and normal tissues were positively correlated with such differences for %RNA, both for the overall data and within three of the four organ sites. However, significant differences in %P and %RNA between malignant and normal tissues were not seen in liver and kidney and, overall, RNA contributed only approximately 11% of total tissue P content. CONCLUSIONS/SIGNIFICANCE: Data for lung and colon tumors provide support for the GRH in human cancer. The two-fold amplification of P content in colon and lung tumors may set the stage for potential P-limitation of their proliferation, as such differences often do for rapidly growing biota in ecosystems. However, data for kidney and liver do not support the GRH. To account for these conflicting observations, we suggest that local environments in some organs select for neoplastic cells bearing mutations increasing cell division rate ("r-selected," as in colon and lung while conditions elsewhere may select for reduced mortality rate ("K-selected," as in liver and

  18. 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.

  19. Precursor lesions in pancreatic cancer: morphological and molecular pathology.

    Science.gov (United States)

    Scarlett, Christopher J; Salisbury, Elizabeth L; Biankin, Andrew V; Kench, James

    2011-04-01

    Pancreatic cancer has a dismal prognosis and is the fourth most common cause of cancer related death in Western societies. In large part this is due to its typically late presentation, usually as locally advanced or metastatic disease. Identification of the non-invasive precursor lesions to pancreatic cancer raises the possibility of surgical treatment or chemoprevention at an early stage in the evolution of this disease, when more amenable to therapeutic interventions. Precursor lesions to pancreatic ductal adenocarcinoma, in particular pancreatic intraepithelial neoplasia (PanIN), have been recognised under a variety of synonyms for over 50 years. Over the past decade our understanding of the morphology, biological significance and molecular aberrations of these lesions has grown rapidly and there is now a widely accepted progression model integrating the accumulated morphological and molecular observations. Further progress is likely to be accelerated by improved mouse models of pancreatic cancer and by insight into the cancer genome gained by the International Cancer Genome Consortium (ICGC), in which an Australian consortium is leading the pancreatic cancer initiative. This review also outlines the morphological and molecular features of the other two precursors of pancreatic ductal adenocarcinoma, i.e., intraductal papillary mucinous neoplasms and mucinous cystic neoplasms.

  20. 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.

  1. The biological sense of cancer: a hypothesis

    Directory of Open Access Journals (Sweden)

    Bustuoabad Oscar D

    2006-12-01

    Full Text Available Abstract Background Most theories about cancer proposed during the last century share a common denominator: cancer is believed to be a biological nonsense for the organism in which it originates, since cancer cells are believed to be ones evading the rules that control normal cell proliferation and differentiation. In this essay, we have challenged this interpretation on the basis that, throughout the animal kingdom, cancer seems to arise only in injured organs and tissues that display lost or diminished regenerative ability. Hypothesis According to our hypothesis, a tumor cell would be the only one able to respond to the demand to proliferate in the organ of origin. It would be surrounded by "normal" aged cells that cannot respond to that signal. According to this interpretation, cancer would have a profound biological sense: it would be the ultimate way to attempt to restore organ functions and structures that have been lost or altered by aging or noxious environmental agents. In this way, the features commonly associated with tumor cells could be reinterpreted as progressively acquired adaptations for responding to a permanent regenerative signal in the context of tissue injury. Analogously, several embryo developmental stages could be dependent on cellular damage and death, which together disrupt the field topography. However, unlike normal structures, cancer would have no physiological value, because the usually poor or non-functional nature of its cells would make their reparative task unattainable. Conclusion The hypothesis advanced in this essay might have significant practical implications. All conventional therapies against cancer attempt to kill all cancer cells. However, according to our hypothesis, the problem might not be solved even if all the tumor cells were eradicated. In effect, if the organ failure remained, new tumor cells would emerge and the tumor would reinitiate its progressive growth in response to the permanent

  2. Molecular Diagnosis in Bladder Cancer

    NARCIS (Netherlands)

    T.C.M. Zuiverloon (Tahlita)

    2013-01-01

    textabstractEpidemiologyBladder cancer (BC) is the most prevalent type of urothelial cancer and is associated with thehighest costs of all cancer types due to intensive patient surveillance. Because bladder tumorsfrequently recur, patients need to be monitored extensively [1-4]. Incidence increases

  3. Molecular imaging of breast cancer

    NARCIS (Netherlands)

    Adams, A.L.L.

    2014-01-01

    Breast cancer is the most common type of cancer in women. Imaging techniques play a pivotal role in breast cancer management, especially in lesion detection, treatment planning and evaluation, and prognostication. These imaging techniques have however limitations such as the use of ionizing radiatio

  4. Advances in the cellular and molecular biology of angiogenesis.

    Science.gov (United States)

    Egginton, Stuart; Bicknell, Roy

    2011-12-01

    Capillaries have been recognized for over a century as one of the most important components in regulating tissue oxygen transport, and their formation or angiogenesis a pivotal element of tissue remodelling during development and adaptation. Clinical interest stems from observations that both excessive and inadequate vascular growth plays a major role in human diseases, and novel developments in treatments for cancer and eye disease increasingly rely on anti-angiogenic therapies. Although the discovery of VEGF (vascular endothelial growth factor) provided the first clue for specificity of signalling in endothelial cell activation, understanding the integrative response that drives angiogenesis requires a much broader perspective. The Advances in the Cellular and Molecular Biology of Angiogenesis meeting brought together researchers at the forefront of this rapidly moving field to provide an update on current understanding, and the most recent insights into molecular and cellular mechanisms of vascular growth. The plenary lecture highlighted the integrative nature of the angiogenic process, whereas invited contributions from basic and clinician scientists described fundamental mechanisms and disease-associated issues of blood vessel formation, grouped under a number of themes to aid discussion. These articles will appeal to academic, clinical and pharmaceutical scientists interested in the molecular and cellular basis of angiogenesis, their modulation or dysfunction in human diseases, and application of these findings towards translational medicine.

  5. 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.

  6. 2003 Archaea: Ecology, Metabolism and Molecular Biology

    Energy Technology Data Exchange (ETDEWEB)

    Richard F. Shand

    2004-09-21

    The Gordon Research Conference (GRC) on 2003 Archaea: Ecology, Metabolism and Molecular Biology was held at Proctor Academy, Andover, NH from August 3-8, 2003. The Conference was well-attended with 150 participants (attendees list attached). The attendees represented the spectrum of endeavor in this field coming from academia, industry, and government laboratories, both U.S. and foreign scientists, senior researchers, young investigators, and students. In designing the formal speakers program, emphasis was placed on current unpublished research and discussion of the future target areas in this field. There was a conscious effort to stimulate lively discussion about the key issues in the field today. Time for formal presentations was limited in the interest of group discussions. In order that more scientists could communicate their most recent results, poster presentation time was scheduled. Attached is a copy of the formal schedule and speaker program and the poster program. In addition to these formal interactions, ''free time'' was scheduled to allow informal discussions. Such discussions are fostering new collaborations and joint efforts in the field. I want to personally thank you for your support of this Conference. As you know, in the interest of promoting the presentation of unpublished and frontier-breaking research, Gordon Research Conferences does not permit publication of meeting proceedings. If you wish any further details, please feel free to contact me. Thank you, Dr. Richard F. Shand, 2003 Conference Chair.

  7. 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.

  8. [New concepts in molecular biology applied to traslational research].

    Science.gov (United States)

    Mengual, Lourdes

    2013-06-01

    This chapter intends to introduce the new concepts that have been established in molecular biology over the last years and are being applied in translational research. The chapter is divided in four big blocks, which treat the molecular biology concepts and techniques in relation to DNA, RNA, proteins and metabolites, respectively. Moreover, we give examples of translational application of these new methodologies described.

  9. A Diagnostic Assessment for Introductory Molecular and Cell Biology

    Science.gov (United States)

    Shi, Jia; Wood, William B.; Martin, Jennifer M.; Guild, Nancy A.; Vicens, Quentin; Knight, Jennifer K.

    2010-01-01

    We have developed and validated a tool for assessing understanding of a selection of fundamental concepts and basic knowledge in undergraduate introductory molecular and cell biology, focusing on areas in which students often have misconceptions. This multiple-choice Introductory Molecular and Cell Biology Assessment (IMCA) instrument is designed…

  10. Commentary: Biochemistry and Molecular Biology Educators Launch National Network

    Science.gov (United States)

    Bailey, Cheryl; Bell, Ellis; Johnson, Margaret; Mattos, Carla; Sears, Duane; White, Harold B.

    2010-01-01

    The American Society of Biochemistry and Molecular Biology (ASBMB) has launched an National Science Foundation (NSF)-funded 5 year project to support biochemistry and molecular biology educators learning what and how students learn. As a part of this initiative, hundreds of life scientists will plan and develop a rich central resource for…

  11. Recent advances in molecular biology of gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    萧树东; 冉志华

    2003-01-01

    Gastric cancer is a major health care problem and the second most common fatal cancer worldwide. In the last decade, better insight has been gained into the molecular basis underlying the neoplasitc transformation of stomach. The dramatic variation in the incidence of gastric cancer in different geographical areas and from one generation to the next have led to the hypothesis that the incidence of gastric cancer is determined largely by environmental rather than genetic factors.

  12. 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.

  13. Exploiting novel molecular targets in gastrointestinal cancers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Novel molecular targets are being discovered as we learn more about the aberrant processes underlying various cancers. Efforts to translate this knowledge are starting to impact on the care of patients with gastrointestinal cancers. The epidermal growth factor receptor (EGFR) pathway and angiogenesis have been targeted successfully in colorectal cancer with cetuximab, panitunumab and bevacizumab. Similarly, EGFR-targeting with erlotinib yielded significant survival benefit in pancreatic cancer when combined with gemcitabine. The multi-targeting approach with sorafenib has made it the first agent to achieve significant survival benefit in hepatocellular carcinoma. Efforts to exploit the dysregulated Akt/mTOR pathway in GI cancer therapy are ongoing. These molecular targets can be disrupted by various approaches, including the use of monoclonal antibody to intercept extracellular ligands and disrupt receptor-ligand binding, and small molecule inhibitors that interrupt the activation of intracellular kinases.

  14. Molecular targeting of acid ceramidase: implications to cancer therapy.

    Science.gov (United States)

    Zeidan, Youssef H; Jenkins, Russell W; Korman, John B; Liu, Xiang; Obeid, Lina M; Norris, James S; Hannun, Yusuf A

    2008-08-01

    Increasingly recognized as bioactive molecules, sphingolipids have been studied in a variety of disease models. The impact of sphingolipids on cancer research facilitated the entry of sphingolipid analogues and enzyme modulators into clinical trials. Owing to its ability to regulate two bioactive sphingolipids, ceramide and sphingosine-1-phosphate, acid ceramidase (AC) emerges as an attractive target for drug development within the sphingolipid metabolic pathway. Indeed, there is extensive evidence supporting a pivotal role for AC in lipid metabolism and cancer biology. In this article, we review the current knowledge of the biochemical properties of AC, its relevance to tumor promotion, and its molecular targeting approaches.

  15. Dynamical Systems and Control Theory Inspired by Molecular Biology

    Science.gov (United States)

    2014-10-02

    in both bacterial and eukaryotic signaling pathways. A common theme in the systems biology literature is that certain systems whose output variables...AFRL-OSR-VA-TR-2014-0282 DYNAMICAL SYSTEMS AND CONTROL THEORY INSPIRED BY MOLECULAR BIOLOGY Eduardo Sontag RUTGERS THE STATE UNIVERSITY OF NEW JERSEY...Standard Form 298 (Re . 8-98) v Prescribed by ANSI Std. Z39.18 DYNAMICAL SYSTEMS AND CONTROL THEORY INSPIRED BY MOLECULAR BIOLOGY AFOSR FA9550-11-1-0247

  16. Molecular biological enhancement of coal biodesulfurization

    Energy Technology Data Exchange (ETDEWEB)

    Litchfield, J.H.; Zupancic, T.J.; Kittle, J.D. Jr.; Baker, B.; Palmer, D.T.; Traunero, C.G.; Wyza, R.E.; Schweitzer, A.; Conkle, H.N. (Battelle, Columbus, OH (United States)); Chakravarty, L.; Tuovinen, O.H. (Ohio State Univ., Columbus, OH (United States))

    1992-10-08

    Progress is reported in understanding Thiobacillus molecular biology, specifically in the area of vector development. At the initiation of this program, the basic elements needed for performing genetic engineering in T. ferrooxidans were either not yet developed. Improved techniques are described which will make it easier to construct and analyze the genetic structure and metabolism of recombinant T. ferrooxidans. The metabolism of the model organic sulfur compound dibenzothiophene (DBT) by certain heterotrophic bacteria was confirmed and characterized. Techniques were developed to analyze the metabolites of DBT, so that individual 4S pathway metabolites could be distinguished. These techniques are expected to be valuable when engineering organic sulfur metabolism in Thiobacillus. Strain isolation techniques were used to develop pure cultures of T. ferrooxidans seven of which were assessed as potential recombinant hosts. The mixotrophic strain T. coprinus was also characterized for potential use as an electroporation host. A family of related Thiobacillus plasmids was discovered in the seven strains of P. ferrooxidans mentioned above. One of these plasmids, pTFI91, was cloned into a pUC-based plasmid vector, allowing it to propagate in E. coli. A key portion of the cloned plasmid was sequenced. This segment, which is conserved in all of the related plasmids characterized, contains the vegetative origin of DNA replication, and fortuitously, a novel insertion sequence, designated IS3091. The sequence of the DNA origin revealed that these Thiobacillus plasmids represent a unique class of replicons not previously described. The potentially useful insertion sequence IS3091 was identified as a new member of a previously undefined family of insertion sequences which include the E. coli element IS30.

  17. Recombinant Platform for Prioritizing Aerolysin Molecular Grenades for Metastatic Prostate Cancer

    Science.gov (United States)

    2015-10-01

    will use a recombinant molecular biology platform to produce a series of molecular grenades, each based upon the bacterial toxin proaerolysin, but...Engineer enzymatically cleavable linker for the release and activation of PA from HSA with lead peptides. Using standard molecular biology techniques to...mouse models. Other avenues of training enrichment include attending the biannual Prostate Cancer United Kingdom meeting which arranged PCa

  18. Role of H2S Donors in Cancer Biology.

    Science.gov (United States)

    Lee, Zheng-Wei; Deng, Lih-Wen

    2015-01-01

    Hydrogen sulfide (H2S) donors including organosulfur compounds (OSC), inorganic sulfide salts, and synthetic compounds are useful tools in studies to elucidate the effects of H2S in cancer biology. Studies using such donors have shown the ability of H2S to suppress tumor growth both in vitro and in vivo, with some of them suggesting the selectivity of its cytotoxic effects to cancer cells. In addition to promoting cancer cell death, H2S donors were also found to inhibit cancer angiogenesis and metastasis. The underlying mechanisms for the anticancer activities of H2S involve (1) cell signaling pathways, such as MAPK and STAT; (2) cell cycle regulation; (3) microRNAs regulation; and (4) cancer metabolism and pH regulation. Altogether, compiling evidences have demonstrated the great potential of using H2S donors as anticancer agents. Nevertheless, the application and development of H2S for therapy are still facing challenges as identification of molecular targets of H2S awaits further investigation.

  19. Terahertz molecular resonance of cancer DNA

    Science.gov (United States)

    Cheon, Hwayeong; Yang, Hee-Jin; Lee, Sang-Hun; Kim, Young A.; Son, Joo-Hiuk

    2016-11-01

    Carcinogenesis involves the chemical and structural alteration of biomolecules in cells. Aberrant methylation of DNA is a well-known carcinogenic mechanism and a common chemical modification of DNA. Terahertz waves can directly observe changes in DNA because the characteristic energies lie in the same frequency region. In addition, terahertz energy levels are not high enough to damage DNA by ionization. Here, we present terahertz molecular resonance fingerprints of DNA methylation in cancer DNA. Methylated cytidine, a nucleoside, has terahertz characteristic energies that give rise to the molecular resonance of methylation in DNA. Molecular resonance is monitored in aqueous solutions of genomic DNA from cancer cell lines using a terahertz time-domain spectroscopic technique. Resonance signals can be quantified to identify the types of cancer cells with a certain degree of DNA methylation. These measurements reveal the existence of molecular resonance fingerprints of cancer DNAs in the terahertz region, which can be utilized for the early diagnosis of cancer cells at the molecular level.

  20. 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.

  1. Molecular Mechanisms of Metastasis Suppression in Human Breast Cancer

    Science.gov (United States)

    2000-07-01

    and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular mechanisms controlling melanoma and breast carcinoma...Bowman Show, August 17 Molecular regulation of melanoma and breast carcinoma metastasis, Wake Forest University Cancer Center, July 28 Molecular...Institute, April 20, Pathology ofNeoplasia Cumberland Unit, American Cancer Society, April 19; Breast Cancer Research Ministerio de Sanidad y

  2. [The Functional Role of Exosomes in Cancer Biology and Their Potential as Biomarkers and Therapeutic Targets of Cancer].

    Science.gov (United States)

    Naito, Yutaka; Yoshioka, Yusuke; Ochiya, Takahiro

    2015-06-01

    Intercellular communication plays an important role in the regulation of various cellular events. In particular, cancer cells and the surrounding cells communicate with each other, and this intercellular communication triggers cancer initiation and progression through the secretion of molecules, including growth factors and cytokines. Recent advances in cancer biology have indicated that small membrane vesicles, termed exosomes, also serve as regulatory agents in intercellular communications. Exosomes contain functional cellular components, including proteins and microRNAs (miRNAs), and they transfer these components to recipient cells. This exosome-mediated intercellular communication leads to increased growth, invasion, and metastasis of cancer. Thus, researchers regard exosomes as important cues to understanding the molecular mechanisms of cancer biology. Indeed, several lines of evidence have demonstrated that exosomes can explain multiple aspects of cancer biology. In addition, increasing evidence suggests that exosomes and their specific molecules are also attractive for use as biomarkers and therapeutic targets in cancer. Recent reports showed the efficacy of a novel diagnosis by detecting component molecules of cancer-derived exosomes, including miRNAs and membrane proteins. Furthermore, clinical trials that test the application of exosomes for cancer therapy have already been reported. From these points of view, we will summarize experimental data that support the role of exosomes in cancer progression and the potential of exosomes for use in novel diagnostic and therapeutic approaches for cancer.

  3. Molecular biology techniques and applications for ocean sensing

    Directory of Open Access Journals (Sweden)

    J. P. Zehr

    2008-11-01

    Full Text Available The study of marine microorganisms using molecular biological techniques is now widespread in the ocean sciences. These techniques target nucleic acids which record the evolutionary history of microbes, and encode for processes which are active in the ocean today. Here we review some of the most commonly used molecular biological techniques. Molecular biological techniques permit study of the abundance, distribution, diversity, and physiology of microorganisms in situ. These techniques include the polymerase chain reaction (PCR and reverse-transcriptase PCR, quantitative PCR, whole assemblage "fingerprinting" approaches (based on nucleic acid sequence or length heterogeneity, oligonucleotide microarrays, and high-throughput shotgun sequencing of whole genomes and gene transcripts, which can be used to answer biological, ecological, evolutionary and biogeochemical questions in the ocean sciences. Moreover, molecular biological approaches may be deployed on ocean sensor platforms and hold promise for tracking of organisms or processes of interest in near-real time.

  4. Acoustic and photoacoustic molecular imaging of cancer.

    Science.gov (United States)

    Wilson, Katheryne E; Wang, Tzu Yin; Willmann, Jürgen K

    2013-11-01

    Ultrasound and combined optical and ultrasonic (photoacoustic) molecular imaging have shown great promise in the visualization and monitoring of cancer through imaging of vascular and extravascular molecular targets. Contrast-enhanced ultrasound with molecularly targeted microbubbles can detect early-stage cancer through the visualization of targets expressed on the angiogenic vasculature of tumors. Ultrasonic molecular imaging can be extended to the imaging of extravascular targets through use of nanoscale, phase-change droplets and photoacoustic imaging, which provides further molecular information on cancer given by the chemical composition of tissues and by targeted nanoparticles that can interact with extravascular tissues at the receptor level. A new generation of targeted contrast agents goes beyond merely increasing imaging signal at the site of target expression but shows activatable and differential contrast depending on their interactions with the tumor microenvironment. These innovations may further improve our ability to detect and characterize tumors. In this review, recent developments in acoustic and photoacoustic molecular imaging of cancer are discussed.

  5. Acoustic and Photoacoustic Molecular Imaging of Cancer

    Science.gov (United States)

    Wilson, Katheryne E.; Wang, Tzu Yin; Willmann, Jürgen K.

    2014-01-01

    Ultrasound and combined optical and ultrasonic (photoacoustic) molecular imaging have shown great promise in the visualization and monitoring of cancer through imaging of vascular and extravascular molecular targets. Contrast-enhanced ultrasound with molecularly targeted microbubbles can detect early-stage cancer through the visualization of targets expressed on the angiogenic vasculature of tumors. Ultrasonic molecular imaging can be extended to the imaging of extravascular targets through use of nanoscale, phase-change droplets and photoacoustic imaging, which provides further molecular information on cancer given by the chemical composition of tissues and by targeted nanoparticles that can interact with extravascular tissues at the receptor level. A new generation of targeted contrast agents goes beyond merely increasing imaging signal at the site of target expression but shows activatable and differential contrast depending on their interactions with the tumor microenvironment. These innovations may further improve our ability to detect and characterize tumors. In this review, recent developments in acoustic and photoacoustic molecular imaging of cancer are discussed. PMID:24187042

  6. Molecular biology of normal melanocytes and melanoma cells.

    Science.gov (United States)

    Bandarchi, Bizhan; Jabbari, Cyrus Aleksandre; Vedadi, Ali; Navab, Roya

    2013-08-01

    Malignant melanoma is one of the most aggressive malignancies in humans and is responsible for 60-80% of deaths from skin cancers. The 5-year survival of patients with metastatic malignant melanoma is about 14%. Its incidence has been increasing in the white population over the past two decades. The mechanisms leading to malignant transformation of melanocytes and melanocytic lesions are poorly understood. In developing malignant melanoma, there is a complex interaction of environmental and endogenous (genetic) factors, including: dysregulation of cell proliferation, programmed cell death (apoptosis) and cell-to-cell interactions. The understanding of genetic alterations in signalling pathways of primary and metastatic malignant melanoma and their interactions may lead to therapeutics modalities, including targeted therapies, particularly in advanced melanomas that have high mortality rates and are often resistant to chemotherapy and radiotherapy. Our knowledge regarding the molecular biology of malignant melanoma has been expanding. Even though several genes involved in melanocyte development may also be associated with melanoma cell development, it is still unclear how a normal melanocyte becomes a melanoma cell. This article reviews the molecular events and recent findings associated with malignant melanoma.

  7. Clinical implications of the intrinsic molecular subtypes of breast cancer.

    Science.gov (United States)

    Prat, Aleix; Pineda, Estela; Adamo, Barbara; Galván, Patricia; Fernández, Aranzazu; Gaba, Lydia; Díez, Marc; Viladot, Margarita; Arance, Ana; Muñoz, Montserrat

    2015-11-01

    Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology. During the last 15 years, 5 intrinsic molecular subtypes of breast cancer (Luminal A, Luminal B, HER2-enriched, Basal-like and Claudin-low) have been identified and intensively studied. In this review, we will focus on the current and future clinical implications of the intrinsic molecular subtypes beyond the current pathological-based classification endorsed by the 2013 St. Gallen Consensus Recommendations. Within hormone receptor-positive and HER2-negative early breast cancer, the Luminal A and B subtypes predict 10-year outcome regardless of systemic treatment administered as well as residual risk of distant recurrence after 5 years of endocrine therapy. Within clinically HER2-positive disease, the 4 main intrinsic subtypes can be identified and dominate the biological and clinical phenotype. From a clinical perspective, patients with HER2+/HER2-enriched disease seem to benefit the most from neoadjuvant trastuzumab, or dual HER2 blockade with trastuzumab/lapatinib, in combination with chemotherapy, and patients with HER2+/Luminal A disease seem to have a relative better outcome compared to the other subtypes. Finally, within triple-negative breast cancer (TNBC), the Basal-like disease predominates (70-80%) and, from a biological perspective, should be considered a cancer-type by itself. Importantly, the distinction between Basal-like versus non-Basal-like within TNBC might predict survival following (neo)adjvuvant multi-agent chemotherapy, bevacizumab benefit in the neoadjuvant setting (CALGB40603), and docetaxel vs. carboplatin benefit in first-line metastatic disease (TNT study). Overall, this data suggests that intrinsic molecular profiling provides clinically relevant information beyond current pathology-based classifications.

  8. Molecular Imaging of Breast Cancer: Present and future directions

    Directory of Open Access Journals (Sweden)

    David eAlcantara

    2014-12-01

    Full Text Available Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumour is located in the body, but also to visualize the expression and activity of specific molecules (e.g. proteases and protein kinases and biological processes (e.g. apoptosis, angiogenesis, and metastasis that influence tumour behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

  9. Molecular biology of liver disorders: the hepatitis C virus and molecular targets for drug development

    Institute of Scientific and Technical Information of China (English)

    Howard J. Worman; Feng Lin

    2000-01-01

    Molecular biology has made a tremendous impact on the diagnosis and treatment of liver diseases[1,2]. In particular, advances in molecular biology made possible the discovery of the virus that causes hepatitis C. In this review, we use hepatitis C as an example of the impact that molecular biology has made in the area of liver disorders. We emphasize how our growing understanding of the hepatitis C virus (HCV) has lead to the identification of targets for development of new treatments.

  10. Review: Biological relevance of disseminated tumor cells in cancer patients.

    Science.gov (United States)

    Riethdorf, Sabine; Wikman, Harriet; Pantel, Klaus

    2008-11-01

    The prognosis of cancer patients is largely determined by the occurrence of distant metastases. In patients with primary tumors, this relapse is mainly due to clinically occult micrometastasis present in secondary organs at primary diagnosis but not detectable even with high resolution imaging procedures. Sensitive and specific immunocytochemical and molecular assays enable the detection and characterization of disseminated tumor cells (DTC) at the single cell level in bone marrow (BM) as the common homing site of DTC and circulating tumor cells (CTC) in peripheral blood. Because of the high variability of results in DTC and CTC detection, there is an urgent need for standardized methods. In this review, we will focus on BM and present currently available methods for the detection and characterization of DTC. Furthermore, we will discuss data on the biology of DTC and the clinical relevance of DTC detection. While the prognostic impact of DTC in BM has clearly been shown for primary breast cancer patients, less is known about the clinical relevance of DTC in patients with other carcinomas. Current findings suggest that DTC are capable to survive chemotherapy and persist in a dormant nonproliferating state over years. To what extent these DTC have stem cell properties is subject of ongoing investigations. Further characterization is required to understand the biology of DTC and to identify new targets for improved risk prevention and tailoring of therapy. Our review will focus on breast, colon, lung, and prostate cancer as the main tumor entities in Europe and the United States.

  11. MOLECULAR PROGNOSTIC MARKERS OF URINE BLADDER CANCER

    Directory of Open Access Journals (Sweden)

    V. N. Pavlov

    2012-01-01

    Full Text Available Bladder cancer (BC remains a current problem in oncourology. Despite that bladder cancer risk factors have been studied and described in the literature, new molecular and genetic mechanisms have been identified that predisposes to the disease development. There are numerous cellular processes involve in BC pathogenesis. The less-aggressive, non-invasive slow progressing bladder cancer types are defined by Ras-MAPK system activation. Tumors that are more aggressive and have low cancer-specific survival rate are characterized by changes in retinoblastoma genes and p53. Attempts are made to develop prognostic tests to predict tumor behavior, targeted treatment. perspectively, BC patients will be treated using molecular genetic markers allowing the accurate prediction of the patient’s tumor behavior and fitting the treatment tactics on the individual basis.

  12. CSMB | Center For Structural Molecular Biology

    Data.gov (United States)

    Federal Laboratory Consortium — The Center for Structural Molecular Biologyat ORNL is dedicated to developing instrumentation and methods for determining the 3-dimensional structures of proteins,...

  13. Molecular and Clinical Markers of Pancreas Cancer

    OpenAIRE

    James L Buxbaum; Eloubeidi, Mohamad A

    2010-01-01

    Pancreas cancer has the worst prognosis of any solid tumor but is potentially treatable if it is diagnosed at an early stage. Thus there is critical interest in delineating clinical and molecular markers of incipient disease. The currently available biomarker, CA 19-9, has an inadequate sensitivity and specificity to achieve this objective. Diabetes mellitus, tobacco use, and chronic pancreatitis are associated with pancreas cancer. However, screening is currently only recommended in those wi...

  14. Assessment of knowledge of participants on basic molecular biology techniques after 5-day intensive molecular biology training workshops in Nigeria.

    Science.gov (United States)

    Yisau, J I; Adagbada, A O; Bamidele, T; Fowora, M; Brai, B I C; Adebesin, O; Bamidele, M; Fesobi, T; Nwaokorie, F O; Ajayi, A; Smith, S I

    2017-02-01

    The deployment of molecular biology techniques for diagnosis and research in Nigeria is faced with a number of challenges, including the cost of equipment and reagents coupled with the dearth of personnel skilled in the procedures and handling of equipment. Short molecular biology training workshops were conducted at the Nigerian Institute of Medical Research (NIMR), to improve the knowledge and skills of laboratory personnel and academics in health, research, and educational facilities. Five-day molecular biology workshops were conducted annually between 2011 and 2014, with participants drawn from health, research facilities, and the academia. The courses consisted of theoretical and practical sessions. The impact of the workshops on knowledge and skill acquisition was evaluated by pre- and post-tests which consisted of 25 multiple choice and other questions. Sixty-five participants took part in the workshops. The mean knowledge of molecular biology as evaluated by the pre- and post-test assessments were 8.4 (95% CI 7.6-9.1) and 13.0 (95 CI 11.9-14.1), respectively. The mean post-test score was significantly greater than the mean pre-test score (p molecular biology workshop significantly increased the knowledge and skills of participants in molecular biology techniques. © 2017 by The International Union of Biochemistry and Molecular Biology, 2017.

  15. Study on the correlation between ultrasonic signs and molecular biological expression in breast cancer%乳腺癌超声征象与分子生物学表达的相关性研究

    Institute of Scientific and Technical Information of China (English)

    王雯; 刘纪锋

    2016-01-01

    Objective:To study the correlation between ultrasonic signs and molecular biological expression in breast cancer ,in order to improve the diagnostic level of breast cancer and provide reliable imaging information for the treatment and prognosis of breast cancer. Methods:Randomly selected 50 cases of pathologically confirmed breast cancer patients and 50 cases healthy person. Breast high frequency ultrasonography was performed in all patients,focusing on observation of tumor morphology,edge, rear echo,microcalcification,internal flow and axillary lymph nodes,all subjects using immunohistochemical assay for the detec-tion of Er,PR,CerbB-2 expression,and analyzed the relationship with their ultrasound imaging findings. Results:①The detection rate of microcalcification in ultrasound was the highest ,and the second was the edge of the burr shape. The detection rate of the tumor of irregular shape was higher when the tumor was greater than 2 cm. ②The positive rate of ER and PR of the as-pect ratio over 1 was 77.8% and 61.1% in the breast cancer group,which was higher than the aspect ratio lower than 1 (P2 cm的肿瘤检出率较高。②肿块纵横比>1患者的ER、PR阳性率为77.8%、61.1%,较纵横比≤1者高(P<0.05);③边缘毛刺征患者的ER、PR阳性率分别为65.5%、55.2%,较无毛刺组高(P<0.05);④周边高回声晕患者的ER和PR阳性率分别为73.3%、60.0%,均高于无高回声晕患者(P<0.05);⑤内部无回声区患者的PR阳性率22.2%,低于未见无回声区患者(P<0.05);⑥微小钙化患者的CerbB-2阳性率83.3%,高于未见微钙化者(P<0.05)。结论:乳腺癌超声表现与分子生物学指标的表达有一定的关系,肿瘤生物学特性影响乳腺癌的超声表现。超声检查可为乳腺癌的预后评估及临床治疗方式的选择提供影像学依据。

  16. [Colorectal cancer (CCR): genetic and molecular alterations].

    Science.gov (United States)

    Juárez-Vázquez, Clara Ibet; Rosales-Reynoso, Mónica Alejandra

    2014-01-01

    The aim of this review is to present a genetic and molecular overview of colorectal carcinogenesis (sporadic and hereditary origin) as a multistage process, where there are a number of molecular mechanisms associated with the development of colorectal cancer and genomic instability that allows the accumulation of mutations in proto-oncogenes and tumor suppressor genes, chromosomal instability, and methylation and microsatellite instability, and the involvement of altered expression of microRNAs' prognosis factors.

  17. [New molecular classification of colorectal cancer, pancreatic cancer and stomach cancer: Towards "à la carte" treatment?].

    Science.gov (United States)

    Dreyer, Chantal; Afchain, Pauline; Trouilloud, Isabelle; André, Thierry

    2016-01-01

    This review reports 3 of recently published molecular classifications of the 3 main gastro-intestinal cancers: gastric, pancreatic and colorectal adenocarcinoma. In colorectal adenocarcinoma, 6 independent classifications were combined to finally hold 4 molecular sub-groups, Consensus Molecular Subtypes (CMS 1-4), linked to various clinical, molecular and survival data. CMS1 (14% MSI with immune activation); CMS2 (37%: canonical with epithelial differentiation and activation of the WNT/MYC pathway); CMS3 (13% metabolic with epithelial differentiation and RAS mutation); CMS4 (23%: mesenchymal with activation of TGFβ pathway and angiogenesis with stromal invasion). In gastric adenocarcinoma, 4 groups were established: subtype "EBV" (9%, high frequency of PIK3CA mutations, hypermetylation and amplification of JAK2, PD-L1 and PD-L2), subtype "MSI" (22%, high rate of mutation), subtype "genomically stable tumor" (20%, diffuse histology type and mutations of RAS and genes encoding integrins and adhesion proteins including CDH1) and subtype "tumors with chromosomal instability" (50%, intestinal type, aneuploidy and receptor tyrosine kinase amplification). In pancreatic adenocarcinomas, a classification in four sub-groups has been proposed, stable subtype (20%, aneuploidy), locally rearranged subtype (30%, focal event on one or two chromosoms), scattered subtype (36%,200 structural variation events, defects in DNA maintenance). Although currently away from the care of patients, these classifications open the way to "à la carte" treatment depending on molecular biology.

  18. Molecular and Clinical Markers of Pancreas Cancer

    Directory of Open Access Journals (Sweden)

    James L Buxbaum

    2010-11-01

    Full Text Available Pancreas cancer has the worst prognosis of any solid tumor but is potentially treatable if it is diagnosed at an early stage. Thus there is critical interest in delineating clinical and molecular markers of incipient disease. The currently available biomarker, CA 19-9, has an inadequate sensitivity and specificity to achieve this objective. Diabetes mellitus, tobacco use, and chronic pancreatitis are associated with pancreas cancer. However, screening is currently only recommended in those with hereditary pancreatitis and genetic syndromes which predispose to cancer. Ongoing work to identify early markers of pancreas cancer consists of high throughput discovery methods including gene arrays and proteomics as well as hypothesis driven methods. While several promising candidates have been identified none has yet been convincingly proven to be better than CA 19-9. New methods including endoscopic ultrasound are improving detection of pancreas cancer and are being used to acquire tissue for biomarker discovery.

  19. Molecular Mechanisms Underlying Psychological Stress and Cancer.

    Science.gov (United States)

    Shin, Kyeong Jin; Lee, Yu Jin; Yang, Yong Ryoul; Park, Seorim; Suh, Pann-Ghill; Follo, Matilde Yung; Cocco, Lucio; Ryu, Sung Ho

    2016-01-01

    Psychological stress is an emotion experienced when people are under mental pressure or encounter unexpected problems. Extreme or repetitive stress increases the risk of developing human disease, including cardiovascular disease (CVD), immune diseases, mental disorders, and cancer. Several studies have shown an association between psychological stress and cancer growth and metastasis in animal models and case studies of cancer patients. Stress induces the secretion of stress-related mediators, such as catecholamine, cortisol, and oxytocin, via the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis or the sympathetic nervous system (SNS). These stress-related hormones and neurotransmitters adversely affect stress-induced tumor progression and cancer therapy. Catecholamine is the primary factor that influences tumor progression. It can regulate diverse cellular signaling pathways through adrenergic receptors (ADRs), which are expressed by several types of cancer cells. Activated ADRs enhance the proliferation and invasion abilities of cancer cells, alter cell activity in the tumor microenvironment, and regulate the interaction between cancer and its microenvironment to promote tumor progression. Additionally, other stress mediators, such as glucocorticoids and oxytocin, and their cognate receptors are involved in stress-induced cancer growth and metastasis. Here, we will review how each receptor-mediated signal cascade contributes to tumor initiation and progression and discuss how we can use these molecular mechanisms for cancer therapy.

  20. Molecular biology techniques and applications for ocean sensing

    Directory of Open Access Journals (Sweden)

    J. P. Zehr

    2009-05-01

    Full Text Available The study of marine microorganisms using molecular biological techniques is now widespread in the ocean sciences. These techniques target nucleic acids which record the evolutionary history of microbes, and encode for processes which are active in the ocean today. Molecular techniques can form the basis of remote instrumentation sensing technologies for marine microbial diversity and ecological function. Here we review some of the most commonly used molecular biological techniques. These techniques include the polymerase chain reaction (PCR and reverse-transcriptase PCR, quantitative PCR, whole assemblage "fingerprinting" approaches (based on nucleic acid sequence or length heterogeneity, oligonucleotide microarrays, and high-throughput shotgun sequencing of whole genomes and gene transcripts, which can be used to answer biological, ecological, evolutionary and biogeochemical questions in the ocean sciences. Moreover, molecular biological approaches may be deployed on ocean sensor platforms and hold promise for tracking of organisms or processes of interest in near-real time.

  1. Molecular markers for prostate cancer.

    NARCIS (Netherlands)

    Reynolds, M.A.; Kastury, K.; Groskopf, J.; Schalken, J.A.; Rittenhouse, H.G.

    2007-01-01

    Serum PSA testing has been used for over 20 years as an aid in the diagnosis and management of prostate cancer. Although highly sensitive, it suffers from a lack of specificity, showing elevated serum levels in a variety of other conditions including prostatitis, benign prostate hyperplasia, and non

  2. 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

  3. The extracellular matrix of plants: Molecular, cellular and developmental biology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-31

    A symposium entitled ``The Extracellular Matrix of Plants: Molecular, Cellular and Developmental Biology was held in Tamarron, Colorado, March 15--21, 1996. The following topics were explored in addresses by 43 speakers: structure and biochemistry of cell walls; biochemistry, molecular biology and biosynthesis of lignin; secretory pathway and synthesis of glycoproteins; biosynthesis of matrix polysaccharides, callose and cellulose; role of the extracellular matrix in plant growth and development; plant cell walls in symbiosis and pathogenesis.

  4. Geometric problems in molecular biology and robotics.

    Science.gov (United States)

    Parsons, D; Canny, J

    1994-01-01

    Some of the geometric problems of interest to molecular biologists have macroscopic analogues in the field of robotics. Two examples of such analogies are those between protein docking and model-based perception, and between ring closure and inverse kinematics. Molecular dynamics simulation, too, has much in common with the study of robot dynamics. In this paper we give a brief survey of recent work on these and related problems.

  5. Systems Cancer Biology and the Controlling Mechanisms for the J-Shaped Cancer Dose Response: Towards Relaxing the LNT Hypothesis

    OpenAIRE

    Lou, In Chio; Zhao, Yuchao; Wu, YingJie; Ricci, Paolo F

    2012-01-01

    The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transforma...

  6. A comprehensive experiment for molecular biology: Determination of single nucleotide polymorphism in human REV3 gene using PCR-RFLP.

    Science.gov (United States)

    Zhang, Xu; Shao, Meng; Gao, Lu; Zhao, Yuanyuan; Sun, Zixuan; Zhou, Liping; Yan, Yongmin; Shao, Qixiang; Xu, Wenrong; Qian, Hui

    2017-02-01

    Laboratory exercise is helpful for medical students to understand the basic principles of molecular biology and to learn about the practical applications of molecular biology. We have designed a lab course on molecular biology about the determination of single nucleotide polymorphism (SNP) in human REV3 gene, the product of which is a subunit of DNA polymerase ζ and SNPs in this gene are associated with altered susceptibility to cancer. This newly designed experiment is composed of three parts, including genomic DNA extraction, gene amplification by PCR, and genotyping by RFLP. By combining these activities, the students are not only able to learn a series of biotechniques in molecular biology, but also acquire the ability to link the learned knowledge with practical applications. This comprehensive experiment will help the medical students improve the conceptual understanding of SNP and the technical understanding of SNP detection. © 2017 by The International Union of Biochemistry and Molecular Biology, 2017.

  7. Biology of breast cancer during pregnancy using genomic profiling.

    Science.gov (United States)

    Azim, Hatem A; Brohée, Sylvain; Peccatori, Fedro A; Desmedt, Christine; Loi, Sherene; Lambrechts, Diether; Dell'Orto, Patrizia; Majjaj, Samira; Jose, Vinu; Rotmensz, Nicole; Ignatiadis, Michail; Pruneri, Giancarlo; Piccart, Martine; Viale, Giuseppe; Sotiriou, Christos

    2014-08-01

    Breast cancer during pregnancy is rare and is associated with relatively poor prognosis. No information is available on its biological features at the genomic level. Using a dataset of 54 pregnant and 113 non-pregnant breast cancer patients, we evaluated the pattern of hot spot somatic mutations and did transcriptomic profiling using Sequenom and Affymetrix respectively. We performed gene set enrichment analysis to evaluate the pathways associated with diagnosis during pregnancy. We also evaluated the expression of selected cancer-related genes in pregnant and non-pregnant patients and correlated the results with changes occurring in the normal breast using a pregnant murine model. We finally investigated aberrations associated with disease-free survival (DFS). No significant differences in mutations were observed. Of the total number of patients, 18.6% of pregnant and 23% of non-pregnant patients had a PIK3CA mutation. Around 30% of tumors were basal, with no differences in the distribution of breast cancer molecular subtypes between pregnant and non-pregnant patients. Two pathways were enriched in tumors diagnosed during pregnancy: the G protein-coupled receptor pathway and the serotonin receptor pathway (FDR pregnancy had higher expression of PD1 (PDCD1; P=0.015), PDL1 (CD274; P=0.014), and gene sets related to SRC (P=0.004), IGF1 (P=0.032), and β-catenin (P=0.019). Their expression increased almost linearly throughout gestation when evaluated on the normal breast using a pregnant mouse model underscoring the potential effect of the breast microenvironment on tumor phenotype. No genes were associated with DFS in a multivariate model, which could be due to low statistical power. Diagnosis during pregnancy impacts the breast cancer transcriptome including potential cancer targets.

  8. Bacteriophages: The viruses for all seasons of molecular biology

    Directory of Open Access Journals (Sweden)

    Karam Jim D

    2005-03-01

    Full Text Available Abstract Bacteriophage research continues to break new ground in our understanding of the basic molecular mechanisms of gene action and biological structure. The abundance of bacteriophages in nature and the diversity of their genomes are two reasons why phage research brims with excitement. The pages of Virology Journal will reflect the excitement of the "New Phage Biology."

  9. Status and Advances of RGD Molecular Imaging in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ning YUE

    2014-12-01

    Full Text Available Lung cancer has been one of the most common and the highest mortality rates malignant tumors at home and abroad. Sustained angiogenesis was not only the characteristic of malignant tumors, but also the foundation of tumor proliferation, invasion, recurrence and metastasis, it was also one of the hot spots of treatments in lung cancer biology currently. Integrins played an important part in tumor angiogenesis. Arg-Gly-Asp (RGD peptides could combine with integrins specifically, and the application of radionuclide-labeled RGD molecular probes enabled imaging of tumor blood vessels to reflect its changes. The lung cancer imaging of RGD peptides at home and abroad in recent years was reviewed in this article.

  10. Molecular markers and targets for colorectal cancer prevention

    Institute of Scientific and Technical Information of China (English)

    Naveena B JANAKIRAM; Chinthalapally V RAO

    2008-01-01

    Colorectal cancer is the third most prevalent cancer in the world. If detected at an early stage, treatment often might lead to cure. As prevention is better than cure, epidemiological studies reveal that having a healthy diet often protects from pro-moting/developing cancer. An important consideration in evaluating new drugs and devices is determining whether a product can effectively treat a targeted disease. There are quite a number of biomarkers making their way into clinical trials and few are awaiting the preclinical efficacy and safety results to enter into clinical trials. Researchers are facing challenges in modifying trial design and defining the right control population, validating biomarker assays from the bio-logical and analytical perspective and using biomarker data as a guideline for decision making. In spite of following all guidelines, the results are disappointing from many of the large clinical trials. To avoid these disappointments, selection of biomarkers and its target drug needs to be evaluated in appropriate animal models for its toxicities and efficacies. The focus of this review is on the few of the potential molecular targets and their biomarkers in colorectal cancers. Strengths and limitations of biomarkers/surrogate endpoints are also discussed. Various pathways involved in tumor cells and the specific agents to target the altered molecular biomarkerin biomolecular pathwayare elucidated. Importance of emerging new platforms siRNAs and miRNAs technology for colorectal cancer therapeutics is reviewed.

  11. The molecular biology of Bluetongue virus replication.

    Science.gov (United States)

    Patel, Avnish; Roy, Polly

    2014-03-01

    The members of Orbivirus genus within the Reoviridae family are arthropod-borne viruses which are responsible for high morbidity and mortality in ruminants. Bluetongue virus (BTV) which causes disease in livestock (sheep, goat, cattle) has been in the forefront of molecular studies for the last three decades and now represents the best understood orbivirus at a molecular and structural level. The complex nature of the virion structure has been well characterised at high resolution along with the definition of the virus encoded enzymes required for RNA replication; the ordered assembly of the capsid shell as well as the protein and genome sequestration required for it; and the role of host proteins in virus entry and virus release. More recent developments of Reverse Genetics and Cell-Free Assembly systems have allowed integration of the accumulated structural and molecular knowledge to be tested at meticulous level, yielding higher insight into basic molecular virology, from which the rational design of safe efficacious vaccines has been possible. This article is centred on the molecular dissection of BTV with a view to understanding the role of each protein in the virus replication cycle. These areas are important in themselves for BTV replication but they also indicate the pathways that related viruses, which includes viruses that are pathogenic to man and animals, might also use providing an informed starting point for intervention or prevention.

  12. Photoactive molecules for applications in molecular imaging and cell biology.

    Science.gov (United States)

    Shao, Qing; Xing, Bengang

    2010-08-01

    Photoactive technology has proven successful for non-invasive regulation of biological activities and processes in living cells. With the light-directed generation of biomaterials or signals, mechanisms in cell biology can be investigated at the molecular level with spatial and temporal resolution. In this tutorial review, we aim to introduce the important applications of photoactive molecules for elucidating cell biology on aspects of protein engineering, fluorescence labelling, gene regulation and cell physiological functions.

  13. Fundamental Approaches in Molecular Biology for Communication Sciences and Disorders

    Science.gov (United States)

    Bartlett, Rebecca S.; Jette, Marie E.; King, Suzanne N.; Schaser, Allison; Thibeault, Susan L.

    2012-01-01

    Purpose: This contemporary tutorial will introduce general principles of molecular biology, common deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein assays and their relevance in the field of communication sciences and disorders. Method: Over the past 2 decades, knowledge of the molecular pathophysiology of human disease has…

  14. Using a Computer Animation to Teach High School Molecular Biology

    Science.gov (United States)

    Rotbain, Yosi; Marbach-Ad, Gili; Stavy, Ruth

    2008-01-01

    We present an active way to use a computer animation in secondary molecular genetics class. For this purpose we developed an activity booklet that helps students to work interactively with a computer animation which deals with abstract concepts and processes in molecular biology. The achievements of the experimental group were compared with those…

  15. [Application of molecular biological techniques in Taenia identification].

    Science.gov (United States)

    Li, Yan; Liu, Hang; Yang, Yi-Mei

    2011-10-01

    The traditional identification of Taenia spp. based on morphological features of adult and cysticercus has difficulties in identifying the morphologically similar species. The recent development of molecular techniques provides more scientific ways for distinguishing Taenia species. This paper summarizes the application of molecular biological techniques in the identification of Taenia, such as analysis of DNA sequence, PCR-RFLP and LAMP.

  16. Molecular biology of human muscle disease

    Energy Technology Data Exchange (ETDEWEB)

    Dunne, P.W.; Epstein, H.F. (Baylor Coll. of Medicine, Houston, TX (United States))

    1991-01-01

    The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the {beta} myosin heavy chain.

  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. Methods in molecular biology: plant cytogenetics

    Science.gov (United States)

    Cytogenetic studies have contributed greatly to our understanding of genetics, biology, reproduction, and evolution. From early studies in basic chromosome behavior the field has expanded enabling whole genome analysis to the manipulation of chromosomes and their organization. This book covers a ran...

  19. Molecular biological enhancement of coal biodesulfurization

    Energy Technology Data Exchange (ETDEWEB)

    Kilbane, J.J. II; Bielaga, B.A.

    1991-12-01

    The overall objective of this project was to use molecular genetics to develop strains of bacteria with enhanced ability to remove sulfur from coal, and to obtain data that will allow the performance and economics of a coal biodesulfurization process to be predicted. (VC)

  20. Molecular cell biology of androgen receptor signalling.

    Science.gov (United States)

    Bennett, Nigel C; Gardiner, Robert A; Hooper, John D; Johnson, David W; Gobe, Glenda C

    2010-06-01

    The classical action of androgen receptor (AR) is to regulate gene transcriptional processes via AR nuclear translocation, response element binding and recruitment of, or crosstalk with, transcription factors. AR also utilises non-classical, non-genomic mechanisms of signal transduction. These precede gene transcription or protein synthesis, and involve steroid-induced modulation of cytoplasmic or cell membrane-bound regulatory proteins. Despite many decades of investigation, the role of AR in gene regulation of cells and tissues remains only partially characterised. AR exerts most of its effects in sex hormone-dependent tissues of the body, but the receptor is also expressed in many tissues not previously thought to be androgen sensitive. Thus it is likely that a complex, more over-arching, role for AR exists. Each AR domain co-ordinates a multitude of individual and vital roles via a diverse array of interacting partner molecules that are necessary for cellular and tissue development and maintenance. Aberrant AR activity, promoted by mutations or binding partner misregulation, can present as many clinical manifestations including androgen insensitivity syndrome and prostate cancer. In the case of malignant prostate cancer, treatment generally revolves around androgen deprivation therapies designed to interfere with AR action and the androgen signalling axis. Androgen therapies for prostate cancer often fail, highlighting a real need for increased research into AR function.

  1. Molecular pathogenesis ofsporadic colorectal cancers

    Institute of Scientific and Technical Information of China (English)

    HidetsuguYamagishi; HajimeKuroda; YasuoImai; HideyukiHiraishi

    2016-01-01

    Colorectal cancer (CRC) results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma. Approximately 75% of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC. During the past two decades, sporadic CRCs were classiifed into three major groups according to frequently altered/mutated genes. These genes have been identiifed by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data. In the ifrst half of this review, we describe the genetic pathways of sporadic CRCs and their clinicopathologic features. Recently, large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes. These infrequently mutated genes are likely described in a lim-ited number of pathways. Gene-oriented models of CRC progression are being replaced by pathway-oriented models. In the second half of this review, we summarize the present knowledge of this research ifeld and discuss its prospects.

  2. 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.

  3. The nucleic acid revolution continues - will forensic biology become forensic molecular biology?

    Science.gov (United States)

    Gunn, Peter; Walsh, Simon; Roux, Claude

    2014-01-01

    Molecular biology has evolved far beyond that which could have been predicted at the time DNA identity testing was established. Indeed we should now perhaps be referring to "forensic molecular biology." Aside from DNA's established role in identifying the "who" in crime investigations, other developments in medical and developmental molecular biology are now ripe for application to forensic challenges. The impact of DNA methylation and other post-fertilization DNA modifications, plus the emerging role of small RNAs in the control of gene expression, is re-writing our understanding of human biology. It is apparent that these emerging technologies will expand forensic molecular biology to allow for inferences about "when" a crime took place and "what" took place. However, just as the introduction of DNA identity testing engendered many challenges, so the expansion of molecular biology into these domains will raise again the issues of scientific validity, interpretation, probative value, and infringement of personal liberties. This Commentary ponders some of these emerging issues, and presents some ideas on how they will affect the conduct of forensic molecular biology in the foreseeable future.

  4. The nucleic acid revolution continues – will forensic biology become forensic molecular biology ?

    Directory of Open Access Journals (Sweden)

    Peter eGunn

    2014-03-01

    Full Text Available Molecular biology has evolved far beyond that which could have been predicted at the time DNA identity testing was established. Indeed we should now perhaps be referring to forensic molecular biology.Aside from DNA’s established role in identifying the who in crime investigations, other developments in medical and developmental molecular biology are now ripe for application to forensic challenges. The impact of DNA methylation and other post-fertilization DNA modifications, plus the emerging role of small RNAs in the control of gene expression, is re-writing our understanding of human biology. It is apparent that these emerging technologies will expand forensic molecular biology to allow for inferences about when a crime took place and what took place.However, just as the introduction of DNA identity testing engendered many challenges, so the expansion of molecular biology into these domains will raise again the issues of scientific validity, interpretation, probative value, and infringement of personal liberties. This Commentary ponders some of these emerging issues, and presents some ideas on how they will affect the conduct of forensic molecular biology in the foreseeable future.

  5. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Abdollahi, H

    2014-06-01

    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.

  6. Molecular aspects of prostate cancer: implications for future directions

    Directory of Open Access Journals (Sweden)

    Etel R. P. Gimba

    2003-10-01

    Full Text Available Many studies have been developed trying to understand the complex molecular mechanisms involved in oncogenesis and progression of prostate cancer (PCa. Current biotechnological methodologies, especially genomic studies, are adding important aspects to this area. The construction of extensive DNA sequence data and gene expression profiles have been intensively explored to search for candidate biomarkers to evaluate PCa. The use of DNA micro-array robotic systems constitutes a powerful approach to simultaneously monitor the expression of a great number of genes. The resulting gene expressing profiles can be used to specifically describe tumor staging and response to cancer therapies. Also, it is possible to follow PCa pathological properties and to identify genes that anticipate the behavior of clinical disease. The molecular pathogenesis of PCa involves many contributing factors, such as alterations in signal transduction pathways, angiogenesis, adhesion molecules expression and cell cycle control. Also, molecular studies are making clear that many genes, scattered through several different chromosomal regions probably cause predisposition to PCa. The discovery of new molecular markers for PCa is another relevant advance resulting from molecular biology studies of prostate tumors. Interesting tissue and serum markers have been reported, resulting in many cases in useful novelties to diagnostic and prognostic approaches to follow-up PCa. Finally, gene therapy comes as an important approach for therapeutic intervention in PCa. Clinical trials for PCa have been demonstrating that gene therapy is relatively safe and well tolerated, although some improvements are yet to be developed.

  7. [Molecular bases of cancer immunology].

    Science.gov (United States)

    Barrera-Rodríguez, R; Peralta-Zaragoza, O; Madrid-Marina, V

    1995-01-01

    The immune system is a tight network of different types of cells and molecules. The coordinated action of these elements mounts a precise immune response against tumor cells. However, these cells present several escape mechanisms, leading to tumor progression. This paper shows several cellular and molecular events involved in the regulation of the immune response against tumor cells. The interaction of several molecules such as MHC, TcR, adhesins, tumor antigens and cytokines are discussed, as well as the most recent knowledge about escape mechanisms and immunotherapy.

  8. Teaching molecular genetics: Chapter 1--Background principles and methods of molecular biology.

    NARCIS (Netherlands)

    Knoers, N.V.A.M.; Monnens, L.A.H.

    2006-01-01

    In this first chapter of the series "Teaching molecular genetics," an introduction to molecular genetics is presented. We describe the structure of DNA and genes and explain in detail the central dogma of molecular biology, that is, the flow of genetic information from DNA via RNA to polypeptide (pr

  9. Cellular and molecular effects of yeast probiotics on cancer.

    Science.gov (United States)

    Saber, Amir; Alipour, Beitollah; Faghfoori, Zeinab; Yari Khosroushahi, Ahmad

    2017-02-01

    The cancer is one of the main causes of human deaths worldwide. The exact mechanisms of initiation and progression of malignancies are not clear yet, but there is a common agreement about the role of colonic microbiota in the etiology of different cancers. Probiotics have been examined for their anti-cancer effects, and different mechanisms have been suggested about their antitumor functions. Nonpathogenic yeasts, as members of probiotics family, can be effective on gut microbiota dysbiosis. Generally safe yeasts have shown so many beneficial effects on human health. Probiotic yeasts influence physiology, metabolism, and immune homeostasis in the colon and contribute to cancer treatment due to possessing anti-inflammatory, anti-proliferative and anti-cancer properties. This study reviews some of the health-beneficial effects of probiotic yeasts and their biological substances like folic acid and β-glucan on cancer and focuses on the possible cellular and molecular mechanisms of probiotic yeasts such as influencing pathogenic bacteria, inactivation of carcinogenic compounds, especially those derived from food, improvement of intestinal barrier function, modulation of immune responses, antitoxic function, apoptosis, and anti-proliferative effects.

  10. MicroRNAs as molecular markers in lung cancer

    Directory of Open Access Journals (Sweden)

    Javier Silva

    2013-10-01

    Full Text Available Lung cancer is the most common cause of cancer death in the western world for both men and women. Lung cancer appears to be a perfect candidate for a screening program, since it is the number one cancer killer, it has a long preclinical phase, curative treatment for the minority of patients who are diagnosed early and a target population at risk (smokers and it is also a major economic burden. The earliest approaches to identifying cancer markers were based on preliminary clinical or pathological observations, although molecular biology is a strong candidate for occupying a place among the set of methods. In search of markers, several alterations, such as mutations, loss of heterozygosity, microsatellite instability, DNA methylation, mitochondrial DNA mutations, viral DNA, modified expression of mRNA, miRNA and proteins, and structurally altered proteins have all been analysed. MicroRNAs (miRNA are small RNA molecules, about 19-25 nucleotides long and encoded in genomes of plants, animals, fungi and viruses. It has been reported that miRNAs may have multiple functions in lung development and that aberrant expression of miRNAs could induce lung tumorigenesis. We review here the role of miRNAs in lung tumorigenesis and also as a novel type of biomarker.-----------------------------------Cite this article as:Silva J, Garcia V, Lopez-Gonzalez A, Provencio M. MicroRNAs as molecular markers in lung cancer. Int J Cancer Ther Oncol 2013;1(1:010111. DOI: http://dx.doi.org/10.14319/ijcto.0101.11

  11. The molecular biology of WHO grade I astrocytomas.

    Science.gov (United States)

    Marko, Nicholas F; Weil, Robert J

    2012-12-01

    World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.

  12. Deciphering molecular determinants of chemotherapy in gastrointestinal malignancy using systems biology approaches.

    Science.gov (United States)

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

    2014-09-01

    Gastrointestinal cancers are asymptomatic in early tumor development, leading to high mortality rates. Peri- or postoperative chemotherapy is a common strategy used to prolong the life expectancy of patients with these diseases. Understanding the molecular mechanisms by which anticancer drugs exert their effect is crucial to the development of anticancer therapies, especially when drug resistance occurs and an alternative drug is needed. By integrating high-throughput techniques and computational modeling to explore biological systems at different levels, from gene expressions to networks, systems biology approaches have been successfully applied in various fields of cancer research. In this review, we highlight chemotherapy studies that reveal potential signatures using microarray analysis, next-generation sequencing (NGS), proteomic and metabolomic approaches for the treatment of gastrointestinal cancers.

  13. Molecular Link between Vitamin D and Cancer Prevention

    Directory of Open Access Journals (Sweden)

    William B. Grant

    2013-09-01

    Full Text Available The metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (also known as calcitriol, is a biologically active molecule required to maintain the physiological functions of several target tissues in the human body from conception to adulthood. Its molecular mode of action ranges from immediate nongenomic responses to longer term mechanisms that exert persistent genomic effects. The genomic mechanisms of vitamin D action rely on cross talk between 1α,25-dihydroxyvitamin D3 signaling pathways and that of other growth factors or hormones that collectively regulate cell proliferation, differentiation and cell survival. In vitro and in vivo studies demonstrate a role for vitamin D (calcitriol in modulating cellular growth and development. Vitamin D (calcitriol acts as an antiproliferative agent in many tissues and significantly slows malignant cellular growth. Moreover, epidemiological studies have suggested that ultraviolet-B exposure can help reduce cancer risk and prevalence, indicating a potential role for vitamin D as a feasible agent to prevent cancer incidence and recurrence. With the preventive potential of this biologically active agent, we suggest that countries where cancer is on the rise—yet where sunlight and, hence, vitamin D may be easily acquired—adopt awareness, education and implementation strategies to increase supplementation with vitamin D in all age groups as a preventive measure to reduce cancer risk and prevalence.

  14. Asymmetry at the molecular level in biology

    Science.gov (United States)

    Johnson, Louise N.

    2005-10-01

    Naturally occurring biological molecules are made of homochiral building blocks. Proteins are composed of L-amino acids (and not D-amino acids); nucleic acids such as DNA have D-ribose sugars (and not L-ribose sugars). It is not clear why nature selected a particular chirality. Selection could have occurred by chance or as a consequence of basic physical chemistry. Possible proposals, including the contribution of the parity violating the weak nuclear force, are discussed together with the mechanisms by which this very small contribution might be amplified. Homochirality of the amino acids has consequences for protein structure. Helices are right handed and beta sheets have a left-hand twist. When incorporated into the tertiary structure of a protein these chiralities limit the topologies of connections between helices and sheets. Polypeptides comprised of D-amino acids can be synthesized chemically and have been shown to adopt stable structures that are the mirror image of the naturally occurring L-amino acid polypeptides. Chirality is important in drug design. Three examples are discussed: penicillin; the CD4 antagonistic peptides; and thalidomide. The absolute hand of a biological structure can only be established by X-ray crystallographic methods using the technique of anomalous scattering.

  15. pGLO Mutagenesis: A Laboratory Procedure in Molecular Biology for Biology Students

    Science.gov (United States)

    Bassiri, Eby A.

    2011-01-01

    A five-session laboratory project was designed to familiarize or increase the laboratory proficiency of biology students and others with techniques and instruments commonly used in molecular biology research laboratories and industries. In this project, the EZ-Tn5 transposon is used to generate and screen a large number of cells transformed with…

  16. Urinary bladder cancer in dogs, a naturally occurring model for cancer biology and drug development.

    Science.gov (United States)

    Knapp, Deborah W; Ramos-Vara, José A; Moore, George E; Dhawan, Deepika; Bonney, Patty L; Young, Kirsten E

    2014-01-01

    Each year more than 65,000 people are diagnosed with urinary bladder cancer, and more than 14,000 people die from the disease in the United States. Studies in relevant animal models are essential to improve the management of bladder cancer. Naturally occurring bladder cancer in dogs very closely mimics human invasive bladder cancer, specifically high-grade invasive transitional cell carcinoma (TCC; also referred to as invasive urothelial carcinoma) in cellular and molecular features; biological behavior, including sites and frequency of metastasis; and response to therapy. Canine bladder cancer complements experimentally induced rodent tumors in regard to animal models of bladder cancer. Results of cellular and molecular studies and -omics analyses in dogs are expected to lead to improved detection of TCC and preneoplastic lesions, earlier intervention, better prediction of patient outcome, and more effective TCC management overall. Studies in dogs are being used to help define heritable risks (through very strong breed-associated risk) and environment risks and to evaluate prevention and treatment approaches that benefit humans as well as dogs. Clinical treatment trials in pet dogs with TCC are considered a win-win scenario by clinician scientists and pet owners. The individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to ultimately help humans with TCC. This article provides an overview of canine TCC, a summary of the similarities and differences between canine and human invasive TCC, and examples of the types of valuable translational research that can be done using dogs with naturally occurring TCC.

  17. Cellular and molecular aspects of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Malcolm G Smith; Georgina L Hold; Eiichi Tahara; Emad M El-Omar

    2006-01-01

    Gastric cancer remains a global killer with a shifting burden from the developed to the developing world.The cancer develops along a multistage process that is defined by distinct histological and pathophysiological phases. Several genetic and epigenetic alterations mediate the transition from one stage to another and these include mutations in oncogenes, tumour suppressor genes and cell cycle and mismatch repair genes. The most significant advance in the fight against gastric caner came with the recognition of the role of Helicobacter pylori (H pylori) as the most important acquired aetiological agent for this cancer. Recent work has focussed on elucidating the complex host/microbial interactions that underlie the neoplastic process. There is now considerable insight into the pathogenesis of this cancer and the prospect of preventing and eradicating the disease has become a reality. Perhaps more importantly, the study of H pylori-induced gastric carcinogenesis offers a paradigm for understanding more complex human cancers. In this review, we examine the molecular and cellular events that underlie H pyloriinduced gastric cancer.

  18. Overview of selected molecular biological databases

    Energy Technology Data Exchange (ETDEWEB)

    Rayl, K.D.; Gaasterland, T.

    1994-11-01

    This paper presents an overview of the purpose, content, and design of a subset of the currently available biological databases, with an emphasis on protein databases. Databases included in this summary are 3D-ALI, Berlin RNA databank, Blocks, DSSP, EMBL Nucleotide Database, EMP, ENZYME, FSSP, GDB, GenBank, HSSP, LiMB, PDB, PIR, PKCDD, ProSite, and SWISS-PROT. The goal is to provide a starting point for researchers who wish to take advantage of the myriad available databases. Rather than providing a complete explanation of each database, we present its content and form by explaining the details of typical entries. Pointers to more complete ``user guides`` are included, along with general information on where to search for a new database.

  19. The molecular biology of WHO grade II gliomas.

    Science.gov (United States)

    Marko, Nicholas F; Weil, Robert J

    2013-02-01

    The WHO grading scheme for glial neoplasms assigns Grade II to 5 distinct tumors of astrocytic or oligodendroglial lineage: diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, pleomorphic xanthoastrocytoma, and pilomyxoid astrocytoma. Although commonly referred to collectively as among the "low-grade gliomas," these 5 tumors represent molecularly and clinically unique entities. Each is the subject of active basic research aimed at developing a more complete understanding of its molecular biology, and the pace of such research continues to accelerate. Additionally, because managing and predicting the course of these tumors has historically proven challenging, translational research regarding Grade II gliomas continues in the hopes of identifying novel molecular features that can better inform diagnostic, prognostic, and therapeutic strategies. Unfortunately, the basic and translational literature regarding the molecular biology of WHO Grade II gliomas remains nebulous. The authors' goal for this review was to present a comprehensive discussion of current knowledge regarding the molecular characteristics of these 5 WHO Grade II tumors on the chromosomal, genomic, and epigenomic levels. Additionally, they discuss the emerging evidence suggesting molecular differences between adult and pediatric Grade II gliomas. Finally, they present an overview of current strategies for using molecular data to classify low-grade gliomas into clinically relevant categories based on tumor biology.

  20. Molecular biology of testicular germ cell tumors.

    Science.gov (United States)

    Gonzalez-Exposito, R; Merino, M; Aguayo, C

    2016-06-01

    Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.

  1. Molecular mechanisms of metastasis in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Noel W.Clarke; Claire A.Hart; Mick D.Brown

    2009-01-01

    Prostate cancer (PCa) preferentially metastasizes to the bone marrow stroma of the axial skeleton.This activity is the principal cause of PCa morbidity and mortality.The exact mechanism of PCa metastasis is currently unknown,although considerable progress has been made in determining the key players in this process.In this review,we present the current understanding of the molecular processes driving PCa metastasis to the bone.

  2. Predictive and prognostic molecular markers for cancer medicine.

    Science.gov (United States)

    Mehta, Sunali; Shelling, Andrew; Muthukaruppan, Anita; Lasham, Annette; Blenkiron, Cherie; Laking, George; Print, Cristin

    2010-03-01

    Over the last 10 years there has been an explosion of information about the molecular biology of cancer. A challenge in oncology is to translate this information into advances in patient care. While there are well-formed routes for translating new molecular information into drug therapy, the routes for translating new information into sensitive and specific diagnostic, prognostic and predictive tests are still being developed. Similarly, the science of using tumor molecular profiles to select clinical trial participants or to optimize therapy for individual patients is still in its infancy. This review will summarize the current technologies for predicting treatment response and prognosis in cancer medicine, and outline what the future may hold. It will also highlight the potential importance of methods that can integrate molecular, histopathological and clinical information into a synergistic understanding of tumor progression. While these possibilities are without doubt exciting, significant challenges remain if we are to implement them with a strong evidence base in a widely available and cost-effective manner.

  3. A decade of molecular cell biology: achievements and challenges.

    Science.gov (United States)

    Akhtar, Asifa; Fuchs, Elaine; Mitchison, Tim; Shaw, Reuben J; St Johnston, Daniel; Strasser, Andreas; Taylor, Susan; Walczak, Claire; Zerial, Marino

    2011-09-23

    Nature Reviews Molecular Cell Biology celebrated its 10-year anniversary during this past year with a series of specially commissioned articles. To complement this, here we have asked researchers from across the field for their insights into how molecular cell biology research has evolved during this past decade, the key concepts that have emerged and the most promising interfaces that have developed. Their comments highlight the broad impact that particular advances have had, some of the basic understanding that we still require, and the collaborative approaches that will be essential for driving the field forward.

  4. Molecular Classification of Gastric Cancer: A new paradigm

    Science.gov (United States)

    Shah, Manish A.; Khanin, Raya; Tang, Laura; Janjigian, Yelena Y.; Klimstra, David S.; Gerdes, Hans; Kelsen, David P.

    2011-01-01

    Purpose Gastric cancer may be subdivided into three distinct subtypes –proximal, diffuse, and distal gastric cancer– based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis. Experimental Design Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (NCI 5917) underwent endoscopic biopsy for fresh tumor procurement. 4–6 targeted biopsies of the primary tumor were obtained. Macrodissection was performed to ensure >80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package. Results Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the three gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross validation error was 0.14, suggesting that >85% of samples were classified correctly. Gene set analysis with the False Discovery Rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach. Conclusions Subtypes of gastric cancer that have epidemiologic and histologic distinction are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. PMID:21430069

  5. Systems Biology and Cancer Prevention: All Options on the Table

    Directory of Open Access Journals (Sweden)

    Simon Rosenfeld

    2008-01-01

    Full Text Available In this paper, we outline the status quo and approaches to further development of the systems biology concepts with focus on applications in cancer prevention science. We discuss the biological aspects of cancer research that are of primary importance in cancer prevention, motivations for their mathematical modeling and some recent advances in computational oncology. We also make an attempt to outline in big conceptual terms the contours of future work aimed at creation of large-scale computational and informational infrastructure for using as a routine tool in cancer prevention science and decision making.

  6. A possible molecular metric for biological evolvability

    Indian Academy of Sciences (India)

    Aditya Mittal; B Jayaram

    2012-07-01

    Proteins manifest themselves as phenotypic traits, retained or lost in living systems via evolutionary pressures. Simply put, survival is essentially the ability of a living system to synthesize a functional protein that allows for a response to environmental perturbations (adaptation). Loss of functional proteins leads to extinction. Currently there are no universally applicable quantitative metrics at the molecular level for either measuring ‘evolvability’ of life or for assessing the conditions under which a living system would go extinct and why. In this work, we show emergence of the first such metric by utilizing the recently discovered stoichiometric margin of life for all known naturally occurring (and functional) proteins. The constraint of having well-defined stoichiometries of the 20 amino acids in naturally occurring protein sequences requires utilization of the full scope of degeneracy in the genetic code, i.e. usage of all codons coding for an amino acid, by only 11 of the 20 amino acids. This shows that the non-availability of individual codons for these 11 amino acids would disturb the fine stoichiometric balance resulting in non-functional proteins and hence extinction. Remarkably, these amino acids are found in close proximity of any given amino acid in the backbones of thousands of known crystal structures of folded proteins. On the other hand, stoichiometry of the remaining 9 amino acids, found to be farther/distal from any given amino acid in backbones of folded proteins, is maintained independent of the number of codons available to synthesize them, thereby providing some robustness and hence survivability.

  7. Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Qingqing Meng

    2013-01-01

    Full Text Available Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular events in vivo. Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained.

  8. Molecular targeted therapy in gastrointestinal cancer%胃肠癌分子靶向治疗

    Institute of Scientific and Technical Information of China (English)

    Miao Xiang; Ximing Xu

    2011-01-01

    Gastrointestinal cancer is one of the highly prevalent malignant diseases worldwide which is a major cause of morbidity and mortality. Gastric cancer is the second leading cause of cancer mortality in the world and its management,especially in advanced stages, has evolved relatively little [1]. Colorectal cancer (CRC) remains the third most common malignancy and the third leading cause of cancer death worldwide [2]. The surgical treatment is still the most effective therapy for the gastrointestinal cancer. However, the majority of the patients had lost the opporunity of surgical therapy when it was detected at advanced stage, so to seek means other than surgical treatment of gastrointestinal cancer metastasis and recurrence also has an important significance. With the deeping research of the molecular biology, molecular targeted therapy has become the hotspot and focus of comprehensive treatment of gastrointestinal cancer which is proposed against the molecular biological targets such as tumor cell growth, apoptosis, cell cycle, invasion and angiogenesis. Molecular targeted therapy can be grouped into six main areas: the epidermal growth factor receptor (EGFR) inhibitors, anti-angiogenic factors, cell cycle inhibitors, apoptosis promoters and matrix metalloproteinase innhibitors, cyclooxygenase inhibitors. The review of the progress are as follows.

  9. Zsyntax: a formal language for molecular biology with projected applications in text mining and biological prediction.

    Directory of Open Access Journals (Sweden)

    Giovanni Boniolo

    Full Text Available We propose a formal language that allows for transposing biological information precisely and rigorously into machine-readable information. This language, which we call Zsyntax (where Z stands for the Greek word zetaomegaeta, life, is grounded on a particular type of non-classical logic, and it can be used to write algorithms and computer programs. We present it as a first step towards a comprehensive formal language for molecular biology in which any biological process can be written and analyzed as a sort of logical "deduction". Moreover, we illustrate the potential value of this language, both in the field of text mining and in that of biological prediction.

  10. A Biochemistry and Molecular Biology Course for Secondary School Teachers

    Science.gov (United States)

    Fernandez-Novell, J. M.; Cid, E.; Gomis, R.; Barbera, A.; Guinovart, J. J.

    2004-01-01

    This article describes a course for reinforcing the knowledge of biochemistry in secondary school science teachers. The Department of Biochemistry and Molecular Biology of the University of Barcelona designed a course to bring these teachers up to date with this discipline. In addition to updating their knowledge of biochemistry and molecular…

  11. A Streamlined Molecular Biology Module for Undergraduate Biochemistry Labs

    Science.gov (United States)

    Muth, Gregory W.; Chihade, Joseph W.

    2008-01-01

    Site-directed mutagenesis and other molecular biology techniques, including plasmid manipulation and restriction analysis, are commonly used tools in the biochemistry research laboratory. In redesigning our biochemistry lab curricula, we sought to integrate these techniques into a term-long, project-based course. In the module presented here,…

  12. Assessing Practical Laboratory Skills in Undergraduate Molecular Biology Courses

    Science.gov (United States)

    Hunt, Lynne; Koenders, Annette; Gynnild, Vidar

    2012-01-01

    This study explored a new strategy of assessing laboratory skills in a molecular biology course to improve: student effort in preparation for and participation in laboratory work; valid evaluation of learning outcomes; and students' employment prospects through provision of evidence of their skills. Previously, assessment was based on written…

  13. Frontiers in nuclear medicine symposium: Nuclear medicine & molecular biology

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-04-01

    This document contains the abstracts from the American College of Nuclear Physicians 1993 Fall Meeting entitled, `Frontiers in Nuclear Medicine Symposium: Nuclear Medicine and Molecular Biology`. This meeting was sponsored by the US DOE, Office of Health and Environmental Research, Office of Energy Research. The program chairman was Richard C. Reba, M.D.

  14. Web Based Learning Support for Experimental Design in Molecular Biology.

    Science.gov (United States)

    Wilmsen, Tinri; Bisseling, Ton; Hartog, Rob

    An important learning goal of a molecular biology curriculum is a certain proficiency level in experimental design. Currently students are confronted with experimental approaches in textbooks, in lectures and in the laboratory. However, most students do not reach a satisfactory level of competence in the design of experimental approaches. This…

  15. Gene Concepts in Higher Education Cell and Molecular Biology Textbooks

    Science.gov (United States)

    Albuquerque, Pitombo Maiana; de Almeida, Ana Maria Rocha; El-Hani, Nino Charbel

    2008-01-01

    Despite being a landmark of 20th century biology, the "classical molecular gene concept," according to which a gene is a stretch of DNA encoding a functional product, which may be a single polypeptide or RNA molecule, has been recently challenged by a series of findings (e.g., split genes, alternative splicing, overlapping and nested…

  16. From Molecular Biology to Biomedicine; De la Biologia Molecular a la Biomedicina

    Energy Technology Data Exchange (ETDEWEB)

    Salas, M.

    2009-07-01

    From Molecular Biology to Biomedicine. The well known molecular biologist Margarita S alas offered an informative conference at the CSN on progress in these areas since the discovery, more than half a century ago, of the structure of the molecule carrying genetic information, DNA, work that is having an enormous impact in areas such as biomedicine and foodstuff production. (Author)

  17. tRNA--the golden standard in molecular biology.

    Science.gov (United States)

    Barciszewska, Mirosława Z; Perrigue, Patrick M; Barciszewski, Jan

    2016-01-01

    Transfer RNAs (tRNAs) represent a major class of RNA molecules. Their primary function is to help decode a messenger RNA (mRNA) sequence in order to synthesize protein and thus ensures the precise translation of genetic information that is imprinted in DNA. The discovery of tRNA in the late 1950's provided critical insight into a genetic machinery when little was known about the central dogma of molecular biology. In 1965, Robert Holley determined the first nucleotide sequence of alanine transfer RNA (tRNA(Ala)) which earned him the 1968 Nobel Prize in Physiology or Medicine. Today, tRNA is one of the best described and characterized biological molecules. Here we review some of the key historical events in tRNA research which led to breakthrough discoveries and new developments in molecular biology.

  18. 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.

  19. [Molecular biology in myelodysplastic syndromes and acute myeloid leukemias "smoldering"].

    Science.gov (United States)

    Martinelli, Giovanni; Sartor, Chiara; Papayannidis, Cristina; Iacobucci, Ilaria; Paolini, Stefania; Clissa, Cristina; Ottaviani, Emanuela; Finelli, Carlo

    2014-03-01

    Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic disorders of the myeloid lineage characterized by peripheral cytopenias and frequent leukemic evolution. MDS differ for clinical presentation, disease behavior and progression and this is the reflection of remarkable variability at molecular level. To this moment disease diagnosis is still dependent on bone marrow morphology that, although high concordance rates among experts are reported, remains subjective. Karyotype analysis is mandatory but diagnosis may be difficult in presence of normal karyotype or non-informative cytogenetics. Standardized molecular markers are needed to better define diagnosis, prediction of disease progression and prognosis. Furthermore, a molecular biology analysis could provide an important therapeutic tool towards tailored therapy and new insights in the disease's biology.

  20. Membrane curvature in cell biology: An integration of molecular mechanisms.

    Science.gov (United States)

    Jarsch, Iris K; Daste, Frederic; Gallop, Jennifer L

    2016-08-15

    Curving biological membranes establishes the complex architecture of the cell and mediates membrane traffic to control flux through subcellular compartments. Common molecular mechanisms for bending membranes are evident in different cell biological contexts across eukaryotic phyla. These mechanisms can be intrinsic to the membrane bilayer (either the lipid or protein components) or can be brought about by extrinsic factors, including the cytoskeleton. Here, we review examples of membrane curvature generation in animals, fungi, and plants. We showcase the molecular mechanisms involved and how they collaborate and go on to highlight contexts of curvature that are exciting areas of future research. Lessons from how membranes are bent in yeast and mammals give hints as to the molecular mechanisms we expect to see used by plants and protists.

  1. Cellular and Molecular Biological Approaches to Interpreting Ancient Biomarkers

    Science.gov (United States)

    Newman, Dianne K.; Neubauer, Cajetan; Ricci, Jessica N.; Wu, Chia-Hung; Pearson, Ann

    2016-06-01

    Our ability to read the molecular fossil record has advanced significantly in the past decade. Improvements in biomarker sampling and quantification methods, expansion of molecular sequence databases, and the application of genetic and cellular biological tools to problems in biomarker research have enabled much of this progress. By way of example, we review how attempts to understand the biological function of 2-methylhopanoids in modern bacteria have changed our interpretation of what their molecular fossils tell us about the early history of life. They were once thought to be biomarkers of cyanobacteria and hence the evolution of oxygenic photosynthesis, but we now believe that 2-methylhopanoid biosynthetic capacity originated in the Alphaproteobacteria, that 2-methylhopanoids are regulated in response to stress, and that hopanoid 2-methylation enhances membrane rigidity. We present a new interpretation of 2-methylhopanes that bridges the gap between studies of the functions of 2-methylhopanoids and their patterns of occurrence in the rock record.

  2. Oral cancer: molecular technologies for risk assessment and diagnosis

    Institute of Scientific and Technical Information of China (English)

    Wan Tao Chen

    2008-01-01

    @@ Purpose: The effective biomarkers related to diagnosis, metastasis, drug resistance and irradiation sensitivity of oral cancers will help the pathologist and oncologist to determine the molecular taxonomy diagnosis and design the individualization treatment for the patients with oral cancers.

  3. 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.

  4. Clinical Advances in Molecular Biomarkers for Cancer Diagnosis and Therapy

    OpenAIRE

    Sarkar, Fazlul H.; Philip, Philip A.; Seema Sethi; Shadan Ali

    2013-01-01

    Cancer diagnosis is currently undergoing a paradigm shift with the incorporation of molecular biomarkers as part of routine diagnostic panel. The molecular alteration ranges from those involving the DNA, RNA, microRNAs (miRNAs) and proteins. The miRNAs are recently discovered small non-coding endogenous single-stranded RNAs that critically regulates the development, invasion and metastasis of cancers. They are altered in cancers and have the potential to serve as diagnostic markers for cancer...

  5. 非吸烟者肺癌的流行病学、病因学和分子生物学特点%Characteristics of epidemiology, etiology and molecular biology of lung cancer in nonsmokers

    Institute of Scientific and Technical Information of China (English)

    王瑞娟; 王萍; 张建中

    2009-01-01

    Smoking is the leading cause of lung cancer, while efforts to study the disease in nonsmokers have been limited. The proportion of lung cancer in nonsmokers is increasing with the successful implementation of tobacco control. Current study indicates that there are striking differences in the epidemiological,clinical and molecular characteristics of lung cancer between nonsmokers and smokers,suggesting that they are separate entities.%吸烟已被证实为肺癌发病的主要原因,但对于非吸烟者患病的研究非常有限,而且随着戒烟措施的成功实施,非吸烟者肺癌的比例会逐渐增加.最近研究表明,非吸烟者和吸烟者肺癌在流行病学、临床、分子生物学方面存在明显差异,提示它们有着本质区别.

  6. The role of neutron scattering in molecular and cellular biology

    Science.gov (United States)

    Worcester, D. L.

    1982-09-01

    Neutron scattering measurements of biological macromolecules and materials have provided answers to numerous questions about molecular assemblies and arrangements. Studies of ribosomes, viruses, membranes, and other biological structures are reviewed, with emphasis on the importance of both deuterium labelling and contrast variation with H2O/D2O exchange. Although many studies of biological molecules have been made using contrast variation alone, it is the deuterium labelling experiments that have provided the most precise information and answers to major biological questions. This is largely the result of the low resolution of scattering data and the consequent rapid increase of information content that specific deuterium labelling provides. Procedures for specific deuterium labelling `in vivo' are described for recent work on myelin membranes together with basic aspects of such labelling useful for future research.

  7. Mechanistic modeling confronts the complexity of molecular cell biology.

    Science.gov (United States)

    Phair, Robert D

    2014-11-05

    Mechanistic modeling has the potential to transform how cell biologists contend with the inescapable complexity of modern biology. I am a physiologist-electrical engineer-systems biologist who has been working at the level of cell biology for the past 24 years. This perspective aims 1) to convey why we build models, 2) to enumerate the major approaches to modeling and their philosophical differences, 3) to address some recurrent concerns raised by experimentalists, and then 4) to imagine a future in which teams of experimentalists and modelers build-and subject to exhaustive experimental tests-models covering the entire spectrum from molecular cell biology to human pathophysiology. There is, in my view, no technical obstacle to this future, but it will require some plasticity in the biological research mind-set.

  8. 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.

  9. Molecular markers for thyroid cancer diagnosis, prognosis, and targeted therapy.

    Science.gov (United States)

    Yip, Linwah

    2015-01-01

    Molecular markers including gene expression profiles, somatic gene alterations, and circulating peripheral markers have augmented diagnostic, prognostic, and therapeutic options for thyroid cancer patients.

  10. Molecular profiling of childhood cancer: Biomarkers and novel therapies

    Directory of Open Access Journals (Sweden)

    Federica Saletta

    2014-06-01

    General significance: The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations.

  11. Animal models and therapeutic molecular targets of cancer: utility and limitations

    Directory of Open Access Journals (Sweden)

    Cekanova M

    2014-10-01

    Full Text Available Maria Cekanova, Kusum Rathore Department of Small Animal Clinical Sciences, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN, USA Abstract: Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients. Keywords: mouse cancer model, companion animal cancer model, dogs, cats, molecular targets

  12. 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.

  13. International Conference on Intelligent Systems for Molecular Biology (ISMB)

    Energy Technology Data Exchange (ETDEWEB)

    Goldberg, Debra; Hibbs, Matthew; Kall, Lukas; Komandurglayavilli, Ravikumar; Mahony, Shaun; Marinescu, Voichita; Mayrose, Itay; Minin, Vladimir; Neeman, Yossef; Nimrod, Guy; Novotny, Marian; Opiyo, Stephen; Portugaly, Elon; Sadka, Tali; Sakabe, Noboru; Sarkar, Indra; Schaub, Marc; Shafer, Paul; Shmygelska, Olena; Singer, Gregory; Song, Yun; Soumyaroop, Bhattacharya; Stadler, Michael; Strope, Pooja; Su, Rong; Tabach, Yuval; Tae, Hongseok; Taylor, Todd; Terribilini, Michael; Thomas, Asha; Tran, Nam; Tseng, Tsai-Tien; Vashist, Akshay; Vijaya, Parthiban; Wang, Kai; Wang, Ting; Wei, Lai; Woo, Yong; Wu, Chunlei; Yamanishi, Yoshihiro; Yan, Changhui; Yang, Jack; Yang, Mary; Ye, Ping; Zhang, Miao

    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.

  14. 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.

  15. Time scale of diffusion in molecular and cellular biology

    Science.gov (United States)

    Holcman, D.; Schuss, Z.

    2014-05-01

    Diffusion is the driver of critical biological processes in cellular and molecular biology. The diverse temporal scales of cellular function are determined by vastly diverse spatial scales in most biophysical processes. The latter are due, among others, to small binding sites inside or on the cell membrane or to narrow passages between large cellular compartments. The great disparity in scales is at the root of the difficulty in quantifying cell function from molecular dynamics and from simulations. The coarse-grained time scale of cellular function is determined from molecular diffusion by the mean first passage time of molecular Brownian motion to a small targets or through narrow passages. The narrow escape theory (NET) concerns this issue. The NET is ubiquitous in molecular and cellular biology and is manifested, among others, in chemical reactions, in the calculation of the effective diffusion coefficient of receptors diffusing on a neuronal cell membrane strewn with obstacles, in the quantification of the early steps of viral trafficking, in the regulation of diffusion between the mother and daughter cells during cell division, and many other cases. Brownian trajectories can represent the motion of a molecule, a protein, an ion in solution, a receptor in a cell or on its membrane, and many other biochemical processes. The small target can represent a binding site or an ionic channel, a hidden active site embedded in a complex protein structure, a receptor for a neurotransmitter on the membrane of a neuron, and so on. The mean time to attach to a receptor or activator determines diffusion fluxes that are key regulators of cell function. This review describes physical models of various subcellular microdomains, in which the NET coarse-grains the molecular scale to a higher cellular-level, thus clarifying the role of cell geometry in determining subcellular function.

  16. Fecal Molecular Markers for Colorectal Cancer Screening

    Directory of Open Access Journals (Sweden)

    Rani Kanthan

    2012-01-01

    Full Text Available Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.

  17. Molecular profiling of multiple human cancers defines an inflammatory cancer-associated molecular pattern and uncovers KPNA2 as a uniform poor prognostic cancer marker.

    Directory of Open Access Journals (Sweden)

    Saleh M Rachidi

    Full Text Available BACKGROUND: Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. METHODS AND FINDINGS: Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An "Inflammatory Gene Integrated Score" was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2 is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. CONCLUSION: This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only

  18. Molecular biology of thermosensory transduction in C. elegans.

    Science.gov (United States)

    Aoki, Ichiro; Mori, Ikue

    2015-10-01

    As the environmental temperature prominently influences diverse biological aspects of the animals, thermosensation and the subsequent information processing in the nervous system has attracted much attention in biology. Thermotaxis in the nematode Caenorhabditis elegans is an ideal behavioral paradigm by which to address the molecular mechanism underlying thermosensory transduction. Molecular genetic analysis in combination with other physiological and behavioral studies revealed that sensation of ambient temperature is mediated mainly by cyclic guanosine monophosphate (cGMP) signaling in thermosensory neurons. The information of the previously perceived temperature is also stored within the thermosensory neurons, and the consequence of the comparison between the past and the present temperature is conveyed to the downstream interneurons to further regulate the motor-circuits that encode the locomotion.

  19. Grete Kellenberger-Gujer: Molecular biology research pioneer.

    Science.gov (United States)

    Citi, Sandra; Berg, Douglas E

    2016-01-01

    Grete Kellenberger-Gujer was a Swiss molecular biologist who pioneered fundamental studies of bacteriophage in the mid-20(th) century at the University of Geneva. Her life and career stories are reviewed here, focusing on her fundamental contributions to our early understanding of phage biology via her insightful analyses of phenomena such as the lysogenic state of a temperate phage (λ), genetic recombination, radiation's in vivo consequences, and DNA restriction-modification; on her creative personality and interactions with peers; and how her academic advancement was affected by gender, societal conditions and cultural attitudes of the time. Her story is important scientifically, putting into perspective features of the scientific community from just before the molecular biology era started through its early years, and also sociologically, in illustrating the numerous "glass ceilings" that, especially then, often hampered the advancement of creative women.

  20. 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.

  1. Molecular biological factors in the diagnosis of cervical intraepithelial neoplasias

    Directory of Open Access Journals (Sweden)

    Yu. N. Ponomareva

    2010-01-01

    Full Text Available The authors have made a complex analysis of the molecular biological factors associated with cervical intraepithelial neoplasia. They have revealed that infection by oncogenic human papillomavirus types is associated with suppressed apoptosis and enhanced cellular proliferative activity, which can be effectively used in the diagnosis and prediction of cervical neoplasias to optimize management tac- tics and to improve the results of treatment.

  2. In focus: molecular and cell biology research in China.

    Science.gov (United States)

    Yao, Xuebiao; Li, Dangsheng; Pei, Gang

    2013-09-01

    An interactive, intellectual environment with good funding opportunities is essential for the development and success of basic research. The fast-growing economy and investment in science, together with a visionary plan, have attracted foreign scholars to work in China, motivated world-class Chinese scientists to return and strengthened the country's international collaborations. As a result, molecular and cell biology research in China has evolved rapidly over the past decade.

  3. Molecularly Imprinted Polymers for 5-Fluorouracil Release in Biological Fluids

    OpenAIRE

    Francesco Puoci; Francesca Iemma; Giuseppe Cirillo; Nevio Picci; Pietro Matricardi; Franco Alhaique

    2007-01-01

    The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs) as a controlled release device for 5-fluorouracil (5-FU) in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs). MIPs were synthesized using methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic a...

  4. Molecular Cancer Imaging with Polymeric Nanoassemblies: From Tumor Detection to Theranostics.

    Science.gov (United States)

    Mi, Peng; Wang, Fang; Nishiyama, Nobuhiro; Cabral, Horacio

    2017-01-01

    Several imaging modalities have been widely applied for the detection of cancer and its pathological activity in combination with probes capable of improving the contrast between healthy and cancerous tissues. Biocompatible polymeric nanoassemblies have been developed for precise detection of malignant tumors by enhancing the selectivity and sensitivity of the imaging. Exploiting the compartmentalized structure of the nanoassemblies advantageously allows delivering both imaging and therapeutic agents for cancer multifunctional imaging and theranostics, i.e., the combination of therapy and diagnosis tool on a single platform. Thus, nanoassemblies have high potential not only for cancer molecular imaging but also for tracing nanoparticles in biological systems, studying their biological pathways, gathering pathological information, monitoring therapeutic effects, and guiding pinpoint therapies. In this review, polymeric nanoassemblies for optical imaging, magnetic resonance imaging, multifunctional imaging, and image-guided therapy, emphasizing their role in cancer diagnosis and theranostics are highlighted.

  5. Cadmium concentration in biological media of breast cancer patients.

    Science.gov (United States)

    Strumylaite, Loreta; Bogusevicius, Algirdas; Abdrachmanovas, Olegas; Baranauskiene, Dale; Kregzdyte, Rima; Pranys, Darius; Poskiene, Lina

    2011-01-01

    The study aimed to determine and compare cadmium (Cd) concentration in different biological media of breast cancer and benign breast tumor patients. Concentration of Cd was determined in breast tissue, urine, and blood of 57 breast cancer and 51 benign tumor patients. Two samples of breast tissue from each patient, i.e., tumor and healthy tissue were taken for the analysis. Cd in biological media was determined by atomic absorption spectrometry (Perkin-Elmer, Zeeman 3030). The mean Cd concentration in breast cancer patients was 0.053 μg/g (95% confidence intervals, CI 0.042-0.065) for tumor sample and 0.02 μg/g (95% CI 0.014-0.026) for healthy breast tissue sample (P 0.05). Cd content in malignant tumor significantly differed from that in benign tumor (P Cancer patients with positive estrogen receptors (ERs) had significantly greater concentration of breast tissue Cd compared to patients with negative ERs (P = 0.035). Adjusted for creatinine, Cd in urine was significantly higher in cancer patients than in controls (P cancer patients, a positive Spearman's correlation was found between Cd in tumor and healthy breast tissue, blood (r = 0.44 and r = 0.39, respectively, P cancer patients and number of cigarettes smoked during lifetime was suggestive (r = 0.59, P = 0.075). The data obtained show higher concentration of cadmium in breast tumor and urine of cancer patients and support a possible relationship between cadmium and breast cancer.

  6. The Molecular Biology of Soft-Tissue Sarcomas and Current Trends in Therapy

    Directory of Open Access Journals (Sweden)

    Jorge Quesada

    2012-01-01

    Full Text Available Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors.

  7. Anti-cancer chalcones: Structural and molecular target perspectives.

    Science.gov (United States)

    Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar; Asati, Vivek

    2015-06-15

    Chalcone or (E)-1,3-diphenyl-2-propene-1-one scaffold remained a fascination among researchers in the 21st century due to its simple chemistry, ease of synthesis and a wide variety of promising biological activities. Several natural and (semi) synthetic chalcones have shown anti-cancer activity due to their inhibitory potential against various targets namely ABCG2/P-gp/BCRP, 5α-reductase, aromatase, 17-β-hydroxysteroid dehydrogenase, HDAC/Situin-1, proteasome, VEGF, VEGFR-2 kinase, MMP-2/9, JAK/STAT signaling pathways, CDC25B, tubulin, cathepsin-K, topoisomerase-II, Wnt, NF-κB, B-Raf and mTOR etc. In this review, a comprehensive study on molecular targets/pathways involved in carcinogenesis, mechanism of actions (MOAs), structure activity relationships (SARs) and patents granted have been highlighted. With the knowledge of molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective anti-cancer chalcones.

  8. A comparative cellular and molecular biology of longevity database.

    Science.gov (United States)

    Stuart, Jeffrey A; Liang, Ping; Luo, Xuemei; Page, Melissa M; Gallagher, Emily J; Christoff, Casey A; Robb, Ellen L

    2013-10-01

    Discovering key cellular and molecular traits that promote longevity is a major goal of aging and longevity research. One experimental strategy is to determine which traits have been selected during the evolution of longevity in naturally long-lived animal species. This comparative approach has been applied to lifespan research for nearly four decades, yielding hundreds of datasets describing aspects of cell and molecular biology hypothesized to relate to animal longevity. Here, we introduce a Comparative Cellular and Molecular Biology of Longevity Database, available at ( http://genomics.brocku.ca/ccmbl/ ), as a compendium of comparative cell and molecular data presented in the context of longevity. This open access database will facilitate the meta-analysis of amalgamated datasets using standardized maximum lifespan (MLSP) data (from AnAge). The first edition contains over 800 data records describing experimental measurements of cellular stress resistance, reactive oxygen species metabolism, membrane composition, protein homeostasis, and genome homeostasis as they relate to vertebrate species MLSP. The purpose of this review is to introduce the database and briefly demonstrate its use in the meta-analysis of combined datasets.

  9. A national comparison of biochemistry and molecular biology capstone experiences.

    Science.gov (United States)

    Aguanno, Ann; Mertz, Pamela; Martin, Debra; Bell, Ellis

    2015-01-01

    Recognizing the increasingly integrative nature of the molecular life sciences, the American Society for Biochemistry and Molecular Biology (ASBMB) recommends that Biochemistry and Molecular Biology (BMB) programs develop curricula based on concepts, content, topics, and expected student outcomes, rather than courses. To that end, ASBMB conducted a series of regional workshops to build a BMB Concept Inventory containing validated assessment tools, based on foundational and discipline-specific knowledge and essential skills, for the community to use. A culminating activity, which integrates the educational experience, is often part of undergraduate molecular life science programs. These "capstone" experiences are commonly defined as an attempt to measure student ability to synthesize and integrate acquired knowledge. However, the format, implementation, and approach to outcome assessment of these experiences are quite varied across the nation. Here we report the results of a nation-wide survey on BMB capstone experiences and discuss this in the context of published reports about capstones and the findings of the workshops driving the development of the BMB Concept Inventory. Both the survey results and the published reports reveal that, although capstone practices do vary, certain formats for the experience are used more frequently and similarities in learning objectives were identified. The use of rubrics to measure student learning is also regularly reported, but details about these assessment instruments are sparse in the literature and were not a focus of our survey. Finally, we outline commonalities in the current practice of capstones and suggest the next steps needed to elucidate best practices.

  10. Molecular targeted treatment and radiation therapy for rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Marquardt, Friederike; Roedel, Franz; Capalbo, Gianni; Weiss, Christian; Roedel, Claus [Dept. of Radiation Therapy, Univ. of Frankfurt/Main (Germany)

    2009-06-15

    Background: EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols. Material and methods: cetuximab and bevacizumab have now been incorporated into phase I-II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings. Results: the combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic complete remission have been noted in several phase II studies. The K-ras mutation status and the gene copy number of EGFR may predict tumor response. The toxicity pattern (radiation-induced enteritis, perforations) and surgical complications (wound healing, fistula, bleeding) observed in at least some of the clinical studies with bevacizumab and CRT warrant further investigations. Conclusion: longer follow-up (and, finally, randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates, and toxicity associated with these novel treatment approaches. (orig.)

  11. Molecular Imaging of Prostate Cancer: A Concise Synopsis

    Directory of Open Access Journals (Sweden)

    Hossein Jadvar

    2009-03-01

    Full Text Available Prostate cancer is the most common malignancy in men and continues to be a major public health problem. Imaging of prostate cancer remains particularly challenging owing to disease heterogeneity. Molecular imaging can provide unprecedented opportunities for deciphering the molecular mechanisms that are involved in the development and natural progression of prostate cancer from a localized process to the hormone-refractory metastatic disease. Such understanding will be the key for targeted imaging and therapy and for predicting and evaluating treatment response and prognosis. In this article, we review briefly the contribution of multimodality molecular imaging methods for the in vivo characterization of the pathophysiology of prostate cancer.

  12. Hormono-biological therapy in metastatic breast cancer: preclinical evidence, clinical studies and future directions.

    Science.gov (United States)

    Tonini, Giuseppe; Schiavon, Gaia; Fratto, Maria Elisabetta; Vincenzi, Bruno; Santini, Daniele

    2008-02-01

    Breast cancer growth is regulated by coordinated actions of the estrogen receptor (ER) and various growth factor receptor signalling pathways. This complex interactive signalling potentially explains some of the reasons behind endocrine therapy action and resistance. Recent research into the molecular biology of ER signalling has revealed new molecular targets which, if present in cancer cells, might be additionally targeted using various signal transduction inhibitors to overcome or prevent resistance to endocrine therapy. The dynamic inverse relationship between the expression of ER and growth factor receptors brings more excitement to the potential of restoring ER expression in apparently ER-negative cells by inhibition of growth factor signalling. The multiple pathways involved in activating ERs also provide a rationale for combining endocrine and non-endocrine therapies that block different signalling pathways. Ongoing clinical trials promise to further improve the present care for breast cancer patients.

  13. 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.

  14. 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.

  15. 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.

  16. Early-onset gastric cancers have a different molecular expression profile than conventional gastric cancers

    NARCIS (Netherlands)

    A.N.A. Milne; R. Carvalho; F.M. Morsink; A.R. Musler; W.W.J. de Leng; A. Ristimaki; G.J.A. Offerhaus

    2006-01-01

    Many studies examine the molecular genetics of gastric cancer, but few look at young patients in particular and there is no comparison of molecular expression between early-onset gastric cancer (<= 45 years old) and conventional gastric cancers. Expression of cycloxygenase-2 (COX-2) is elevated in g

  17. Prostate cancer immunology: biology, therapeutics, and challenges.

    Science.gov (United States)

    Webster, W Scott; Small, Eric J; Rini, Brian I; Kwon, Eugene D

    2005-11-10

    A number of recently developed and promising approaches to antitumoral immunotherapy are being investigated as potential treatments for advanced prostate cancer. These approaches largely revolve around strategies to increase antigen-specific T-cell activation against prostate tumors as well as precise manipulations of critical co-regulatory receptors that help to maintain and prolong the activity of antigen-presenting cells and T cells that are capable of mediating tumor regression. Herein, we describe the experience with the most recent and promising approaches pertaining to prostate cancer immunotherapy. Additionally, we discuss the mechanistic basis for these approaches as well as current limitations that must still be addressed in order to propel immunotherapy into the forefront of prostate cancer treatment.

  18. 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.

  19. 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.

  20. Prostate cancer heterogeneity: Discovering novel molecular targets for therapy.

    Science.gov (United States)

    Ciccarese, Chiara; Massari, Francesco; Iacovelli, Roberto; Fiorentino, Michelangelo; Montironi, Rodolfo; Di Nunno, Vincenzo; Giunchi, Francesca; Brunelli, Matteo; Tortora, Giampaolo

    2017-03-01

    Prostate cancer (PCa) shows a broad spectrum of biological and clinical behavior, which represents the epiphenomenon of an extreme genetic heterogeneity. Recent genomic profiling studies have deeply improved the knowledge of the genomic landscape of localized and metastatic PCa. The AR and PI3K/Akt/mTOR signaling pathways are the two most frequently altered, representing therefore interestingly targets for therapy. Moreover, somatic or germline aberrations of DNA repair genes (DRGs) have been observed at high frequency, supporting the potential role of platinum derivatives and PARP inhibitors as effective therapeutic strategies. In the future, the identification of driver mutations present at a specific stage of the disease, the classification PCa based on specific molecular alterations, and the selection of the most appropriate therapy based on biomarkers predictors of response represent the foundations for an increasingly more accurate personalized medicine.

  1. Hormonal and molecular aspects of endometrioid endometrial cancer

    NARCIS (Netherlands)

    Jongen, Vincentius Hubertus Willibrordus Maria

    2008-01-01

    This thesis concerns the expression and prognostic value of various hormones and molecular markers playing a role n endometrioid endometrial cancer. Especially we were interested in the enzyme aromatase, its expression and (prognostic) role in endometrioid endometrial cancer. Endometrial cancer is t

  2. Echoes of the embryo: using the developmental biology toolkit to study cancer

    Directory of Open Access Journals (Sweden)

    Nicole M. Aiello

    2016-02-01

    Full Text Available The hallmark of embryonic development is regulation – the tendency for cells to find their way into organized and ‘well behaved’ structures – whereas cancer is characterized by dysregulation and disorder. At face value, cancer biology and developmental biology would thus seem to have little to do with each other. But if one looks beneath the surface, embryos and cancers share a number of cellular and molecular features. Embryos arise from a single cell and undergo rapid growth involving cell migration and cell-cell interactions: features that are also seen in the context of cancer. Consequently, many of the experimental tools that have been used to study embryogenesis for over a century are well-suited to studying cancer. This article will review the similarities between embryogenesis and cancer progression and discuss how some of the concepts and techniques used to understand embryos are now being adapted to provide insight into tumorigenesis, from the origins of cancer cells to metastasis.

  3. 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.

  4. Molecular Markers with Predictive and Prognostic Relevance in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Alphy Rose-James

    2012-01-01

    Full Text Available Lung cancer accounts for the majority of cancer-related deaths worldwide of which non-small-cell lung carcinoma alone takes a toll of around 85%. Platinum-based therapy is the stronghold for lung cancer at present. The discovery of various molecular alterations that underlie lung cancer has contributed to the development of specifically targeted therapies employing specific mutation inhibitors. Targeted chemotherapy based on molecular profiling has shown great promise in lung cancer treatment. Various molecular markers with predictive and prognostic significance in lung cancer have evolved as a result of advanced research. Testing of EGFR and Kras mutations is now a common practice among community oncologists, and more recently, ALK rearrangements have been added to this group. This paper discusses various predictive and prognostic markers that are being investigated and have shown significant relevance which can be exploited for targeted treatment in lung cancer.

  5. [Molecular Biology on the Mechanisms of Autism Spectrum Disorder for Clinical Psychiatrists].

    Science.gov (United States)

    Makinodan, Manabu

    2015-01-01

    While, in general, a certain number of clinical psychiatrists might not be familiar with molecular biology, the mechanisms of mental illnesses have been uncovered by molecular biology for decades. Among mental illnesses, even biological psychiatrists and neuroscientists have paid less attention to the biological treatment of autism spectrum disorder (ASD) than Alzheimer's disease and schizophrenia since ASD has been regarded as a developmental disorder that was seemingly untreatable. However, multifaceted methods of molecular biology have revealed the mechanisms that would lead to the medication of ASD. In this article, how molecular biology dissects the pathobiology of ASD is described in order to announce the possibilities of biological treatment for clinical psychiatrists.

  6. Biology of lung cancer: genetic mutation, epithelial-mesenchymal transition, and cancer stem cells.

    Science.gov (United States)

    Aoi, Takashi

    2016-09-01

    At present, most cases of unresectable cancer cannot be cured. Genetic mutations, EMT, and cancer stem cells are three major issues linked to poor prognosis in such cases, all connected by inter- and intra-tumor heterogeneity. Issues on inter-/intra-tumor heterogeneity of genetic mutation could be resolved with recent and future technologies of deep sequencers, whereas, regarding such issues as the "same genome, different epigenome/phenotype", we expect to solve many of these problems in the future through further research in stem cell biology. We herein review and discuss the three major issues in the biology of cancers, especially from the standpoint of stem cell biology.

  7. 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.)

  8. Cold Spring Harbor symposia on quantitative biology: Volume L, Molecular biology of development

    Energy Technology Data Exchange (ETDEWEB)

    1985-01-01

    This volume contains contributions by contributors to the 1985 Cold Springs Harbor Symposium on Quantitative Biology. This year's theme was Molecular Biology of Development. The volume consists of 104 articles organized by content into sections entitled Nuclear/Cytoplasmic Interactions in Early Development; Lineage and Segmentation/Pattern Formation; Homeotic Mutants; Homeo Boxes; Tissue Specificity/Position Effects; Expression of Genes Introduced into Transgenic Mice; Induced Developmental Defects; Control of Gene Expression; Sex Determination; Cell-cycle Effects; Pluripotent Cells/Oncogenes; Cellular Differentiation; and Developmental Neurobiology.

  9. Cancer systems biology and modeling: microscopic scale and multiscale approaches.

    Science.gov (United States)

    Masoudi-Nejad, Ali; Bidkhori, Gholamreza; Hosseini Ashtiani, Saman; Najafi, Ali; Bozorgmehr, Joseph H; Wang, Edwin

    2015-02-01

    Cancer has become known as a complex and systematic disease on macroscopic, mesoscopic and microscopic scales. Systems biology employs state-of-the-art computational theories and high-throughput experimental data to model and simulate complex biological procedures such as cancer, which involves genetic and epigenetic, in addition to intracellular and extracellular complex interaction networks. In this paper, different systems biology modeling techniques such as systems of differential equations, stochastic methods, Boolean networks, Petri nets, cellular automata methods and agent-based systems are concisely discussed. We have compared the mentioned formalisms and tried to address the span of applicability they can bear on emerging cancer modeling and simulation approaches. Different scales of cancer modeling, namely, microscopic, mesoscopic and macroscopic scales are explained followed by an illustration of angiogenesis in microscopic scale of the cancer modeling. Then, the modeling of cancer cell proliferation and survival are examined on a microscopic scale and the modeling of multiscale tumor growth is explained along with its advantages.

  10. Towards molecular computers that operate in a biological environment

    Science.gov (United States)

    Kahan, Maya; Gil, Binyamin; Adar, Rivka; Shapiro, Ehud

    2008-07-01

    important consequences when performed in a proper context. We envision that molecular computers that operate in a biological environment can be the basis of “smart drugs”, which are potent drugs that activate only if certain environmental conditions hold. These conditions could include abnormalities in the molecular composition of the biological environment that are indicative of a particular disease. Here we review the research direction that set this vision and attempts to realize it.

  11. 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.

  12. Molecular biology of breast tumors and prognosis [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Gustavo Baldassarre

    2016-04-01

    Full Text Available Breast cancer is the most common cancer among women worldwide. Great scientific, economical, and organizational efforts are in place to understand the causes of onset, identify the critical molecular players of progression, and define new lines of intervention providing more benefits and less toxicity. These efforts have certainly not been vain, since overall survival, especially in specific subsets of breast cancer, has greatly improved during the last decades. At present, breast cancer patients’ treatment and care have reached a high standard of quality, and currently one of the most urgent needs resides in the necessity to better distinguish the tumors that need to be more aggressively treated and identify the best therapeutic option tailored to each patient. This objective will be achievable only if the information clarifying the biology of breast cancer can be successfully transferred to the clinic. A common effort by scientists and clinicians toward this integration and toward the use of multidisciplinary approaches will be necessary to reach this important goal.

  13. Biodiversity: molecular biological domains, symbiosis and kingdom origins

    Science.gov (United States)

    Margulis, L.

    1992-01-01

    The number of extant species of organisms is estimated to be from fewer than 3 to more than 30 x 10(6) (May, 1992). Molecular biology, comparative genetics and ultrastructural analyses provide new insights into evolutionary relationships between these species, including increasingly precise ideas of how species and higher taxa have evolved from common ancestors. Accumulation of random mutations and large macromolecular sequence change in all organisms since the Proterozoic Eon has been importantly supplemented by acquisition of inherited genomes ('symbiogenesis'). Karyotypic alterations (polyploidization and karyotypic fissioning) have been added to these other mechanisms of species origin in plants and animals during the Phanerozoic Eon. The new evolution concepts (coupled with current rapid rates of species extinction and ignorance of the extent of biodiversity) prompted this analysis of the field of systematic biology and its role in the reorganization of extant species into higher taxa. Two superkingdoms (= Domains: Prokaryotae and Eukaryotae) and five kingdoms (Monera = Procaryotae or Bacteria; Protoctista: algae, amoebae, ciliates, foraminifera, oomycetes, slime molds, etc.; Mychota: 'true' fungi; Plantae: one phylum (division) of bryophytes and nine phyla of tracheophytes; and Animalia) are recognized. Two subkingdoms comprise the monera: the great diverse lineages are Archaebacteria and Eubacteria. The criteria for classification using molecular, ultrastructural and genetic data for this scheme are mentioned. For the first time since the nineteenth century, logical, technical definitions for each group are given with their time of appearance as inferred from the fossil record in the primary scientific literature. This classification scheme, which most closely reflects the evolutionary history, molecular biology, genetics and ultrastructure of extant life, requires changes in social organization of biologists, many of whom as botanists and zoologists, still

  14. Research Applications of Proteolytic Enzymes in Molecular Biology

    Directory of Open Access Journals (Sweden)

    József Tőzsér

    2013-11-01

    Full Text Available Proteolytic enzymes (also termed peptidases, proteases and proteinases are capable of hydrolyzing peptide bonds in proteins. They can be found in all living organisms, from viruses to animals and humans. Proteolytic enzymes have great medical and pharmaceutical importance due to their key role in biological processes and in the life-cycle of many pathogens. Proteases are extensively applied enzymes in several sectors of industry and biotechnology, furthermore, numerous research applications require their use, including production of Klenow fragments, peptide synthesis, digestion of unwanted proteins during nucleic acid purification, cell culturing and tissue dissociation, preparation of recombinant antibody fragments for research, diagnostics and therapy, exploration of the structure-function relationships by structural studies, removal of affinity tags from fusion proteins in recombinant protein techniques, peptide sequencing and proteolytic digestion of proteins in proteomics. The aim of this paper is to review the molecular biological aspects of proteolytic enzymes and summarize their applications in the life sciences.

  15. 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.

  16. The molecular biology and diagnostics of Chlamydia trachomatis

    DEFF Research Database (Denmark)

    Birkelund, Svend

    1992-01-01

    The rapid development of biotechnological methods provides the potential of dissecting the molecular structure of microorganisms. In this review the molecular biology of chlamydia is described. The genus Chlamydia contains three species C. trachomatis, C. psittaci, and C. pneumonia which all...... are important human pathogens. Chlamydia is obligate intracellular bacteria with a unique biphasic life cycle. The extracellularly chlamydial elementary bodies (EB) are small, metabolic inactive, infectious particles with a tight outer cell membrane. After internalization into host cells the chlamydial...... since it is highly cross-linked by S-S bridges. There are, however, also similarities to gram-negative cell walls. The chlamydial major outer membrane protein, Omp1, forms pores and is closely associated with lipopolysaccharide, LPS. LPS, however, is more loosely associated with Omp1 than in other gram...

  17. Posttranslational modulation on the biological activities of molecular chaperones

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Molecular chaperones are a family of proteins that were first noticed to exist about 45 years ago from their increased transcription under heat shock conditions.As a result,the regulation of their encoding genes has been subject to extensive studies.Recent studies revealed that the biological activities of molecular chaperones can also be effectively modulated at the protein level.The ways of modulation so far elucidated include allosteric effect,covalent modification,protein-protein interaction,and con-formational alteration induced by such macro-environmental conditions as temperature and pH.These latter aspects were reviewed here.Emphasized here is the importance of such immediate structural alterations that lead to an immediate activity increase,providing the immediate protection needed for the cells to survive the stress conditions.

  18. Posttranslational modulation on the biological activities of molecular chaperones

    Institute of Scientific and Technical Information of China (English)

    CHANG ZengYi

    2009-01-01

    Molecular chaperones are a family of proteins that were first noticed to exist about 45 years ago from their increased transcription under heat shock conditions. As a result, the regulation of their encoding genes has been subject to extensive studies. Recent studies revealed that the biological activities of molecular chaperones can also be effectively modulated at the protein level. The ways of modulation so far elucidated include allosteric effect, covalent modification, protein-protein interaction, and con-formational alteration induced by such macro-environmental conditions as temperature and pH. These latter aspects were reviewed here. Emphasized here is the importance of such immediate structural alterations that lead to an immediate activity increase, providing the immediate protection needed for the cells to survive the stress conditions.

  19. International Symposium on Insect Physiology, Biochemistry and Molecular Biology

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ We are building on the success of the Sixth Chinese Insect Physiology, Biochemistry and Molecular Biology Symposium, Beijing, held in 2005. The 2005 symposium saw many Chinese and international authorities share their expertise in a broad range of insect science, including analyses of insect genomes and proteomes, functional gene expression and regulation during development, insect immunity, insect neurobiology, insect-host interactions and insect chemical communication. The coming symposium, which will be held in Shandong University,Jinan, Shandong province, September 19-22, 2007, will offer material along similar lines.

  20. [Applications of molecular biology in the wine industry].

    Science.gov (United States)

    Ramón, D; González-Candelas, L; Pérez-González, J A; González, R; Ventura, L; Sánchez-Torres, P; Vallés, S; Piñaga, F; Gallego, M V; Fernández-Espinar, M T

    1995-03-01

    Population dynamics of natural and inoculated industrial wine fermentations have been studied by using a simple molecular biology technique based on mitochondrial DNA restriction analysis profile. The predominance of the inoculated strain in the inoculated fermentations is obvious. A genetic transformation system has been developed for an industrial wine yeast strain named T73. By using this technique, different fungal hydrolases in this industrial strain have been expressed. Problems and benefits of the application of recombinant DNA techniques in wine yeast strains are also discussed here.

  1. 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.

  2. New wine in old bottles? The biotechnology problem in the history of molecular biology.

    Science.gov (United States)

    Gaudillière, Jean-Paul

    2009-03-01

    This paper examines the "biotechnology problem" in the history of molecular biology, namely the alleged reinvention of a basic academic discipline looking for the logic of life, into a typical technoscientific enterprise, closely related to agriculture, medicine, and the construction of markets. The dominant STS model sees the roots of this shift in a radical change of the regime of knowledge production. The paper argues that this scheme needs to be historicized to take into account the past in our biotech present. Looking at the development of breast cancer genetic testing and GMOs as examples of mounting issues of intellectual property, risk and regulation, the paper also argues that historians of biology should pay closer attention to the political, the economical and the legal changes of the last thirty years. Solving the biotech problem requires new categories. The notion of "way of regulating" is given as an example of such notions linking the local and the global.

  3. 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.

  4. Radiation oncology--linking technology and biology in the treatment of cancer.

    Science.gov (United States)

    Coleman, C Norman

    2002-01-01

    Technical advances in radiation oncology including CT-simulation, 3D- conformal and intensity-modulated radiation therapy (IMRT) delivery techniques, and brachytherapy have allowed greater treatment precision and dose escalation. The ability to intensify treatment requires the identification of the critical targets within the treatment field, recognizing the unique biology of tumor, stroma and normal tissue. Precision is technology based while accuracy is biologically based. Therefore, the intensity of IMRT will undoubtedly mean an increase in both irradiation dose and the use of biological agents, the latter considered in the broadest sense. Radiation oncology has the potential and the opportunity to provide major contributions to the linkage between molecular and functional imaging, molecular profiling and novel therapeutics for the emerging molecular targets for cancer treatment. This process of 'credentialing' of molecular targets will require multi disciplinary imaging teams, clinicians and basic scientists. Future advances will depend on the appropriate integration of biology into the training of residents, continuing post graduate education, participation in innovative clinical research and commitment to the support of basic research as an essential component of the practice of radiation oncology.

  5. 乳腺癌钼靶X线表现与分子生物学表达的相关性研究%Breast cancer mammography X-ray findings with the expression of molecular biology research

    Institute of Scientific and Technical Information of China (English)

    安丽华; 陈东风; 李静; 时克伟; 赵小春

    2013-01-01

    Objective Biology explore breast cancer mammography X-ray findings with the cancer cells of the estrogen receptor(ER) and progesterone receptor(PR) and human tumor suppressor gene(P53), aimed at early diagnosis and prognosis of breast provide the basis. Methods A retrospective analysis of 152 patients with pathologically proved infiltrating ductal breast cancer study. The patients preoperative mammography X-ray examination focus observed increased lesion mass, calcification, structural disorder, local density. To histopathological results do control. Postoperative specimens Determination ER, PR, P53 expression analysis of the relationship between them with X-ray mammography performance. Results 152 cases of invasive ductal carcinoma, showed a mass with irregular burrs or form associated with the expression of ER, PR(χ2=8.108, P<0.05; χ2=5.571, P<0.05); Calcification significant difference in expression of ER, PR(χ2=4.851, P<0.05; χ2=4.579, P<0.05); Increased breast structural disorder or local density and ER, PR expression difference was statistically significant(χ2=6.521, P<0.05; χ2=5.602, P<0.05). Breast structural disorder or increased local density and P53 expression significant difference(χ2=7.883, P<0.05). Conclusion Breast cancer mammography X-ray findings exists a certain correlation between ER, PR, P53, to some extent, reflect the biological behavior and prognosis of breast cancer cells, to provide more for the early diagnosis and treatment objective basis.%  目的探讨乳腺癌钼靶X线表现与癌细胞雌激素受体(ER)、孕激素受体(PR)及人体抑癌基因(P53)生物学相关性,旨在为乳腺癌的早期诊断及预测预后提供依据.方法回顾性分析经手术病理证实的152例乳腺浸润性导管癌患者为研究对象.患者均于术前行钼靶X线检查,重点观察病变肿块、钙化、结构紊乱、局部密度增高等.以病理组织学结果做对照.术后标本测定ER、PR、P53

  6. Update in Molecular Biology and Biotechnology: providing alternative for Sciences and Biology Teachers

    Directory of Open Access Journals (Sweden)

    M. F. Silva

    2008-05-01

    Full Text Available One of the goals of the Coordination of Education and Dissemination of CBME is to contribute for the dissemination and the learning in Molecular Biology and Biotechnology in  all the educational levels. Thus, composing one of our actions in 2007, a course of update in Molecular Biology and Biotechnology directed to 21 teachers of Sciences and Biology of São Carlos (SP, Brazil was carried through, totalizing 24 hours. In one of the meetings, we presented the techniques involving restriction enzymes, gel electrophoresis and its applications, followed of an experimental activity. Also we constructed and  considered the use, for the teachers, of a macroscopic model of a gel box that would represent the displacement of DNA fragments. After that a written questionnaire was used to evaluate the importance attributed for the teachers to the subject, the possibilities of didactic transposition, as well as their interests for other activities that would deal this thematic at great length. From this,  we registered that the 93% of the teachers showed interest in the subject, considering it important and also, 79% of them affirmed to have possibility of didactic transposition of this subject after they have experienced the course. On the other hand, 86% of the teachers did not work the subject in their classes , amongst which 50% for the lack of time or not enough preparation. Therefore, the data suggest that the course had an impact on the vision of the teachers concerning the alternatives to include the subject Molecular Biology and Biotechnology in their curricular planning.

  7. Obstructive renal injury: from fluid mechanics to molecular cell biology

    Directory of Open Access Journals (Sweden)

    Alvaro C Ucero

    2010-04-01

    Full Text Available Alvaro C Ucero1,*, Sara Gonçalves2,*, Alberto Benito-Martin1, Beatriz Santamaría1, Adrian M Ramos1, Sergio Berzal1, Marta Ruiz-Ortega1, Jesus Egido1, Alberto Ortiz11Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Fundación Renal Iñigo Alvarez de Toledo, Madrid, Spain; 2Nefrologia e Transplantação Renal, Hospital de Santa Maria EPE, Lisbon, Portugal *Both authors contributed equally to the manuscriptAbstract: Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1 and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making.Keywords: urinary tract obstruction, renal injury, fluid mechanics, molecular cell biology

  8. Errant life, molecular biology, and biopower: Canguilhem, Jacob, and Foucault.

    Science.gov (United States)

    Talcott, Samuel

    2014-01-01

    This paper considers the theoretical circumstances that urged Michel Foucault to analyse modern societies in terms of biopower. Georges Canguilhem's account of the relations between science and the living forms an essential starting point for Foucault's own later explorations, though the challenges posed by the molecular revolution in biology and François Jacob's history of it allowed Foucault to extend and transform Canguilhem's philosophy of error. Using archival research into his 1955-1956 course on "Science and Error," I show that, for Canguilhem, it is inauthentic to treat a living being as an error, even if living things are capable of making errors in the domain of knowledge. The emergent molecular biology in the 1960s posed a grave challenge, however, since it suggested that individuals could indeed be errors of genetic reproduction. The paper discusses how Canguilhem and Foucault each responded to this by examining, among other texts, their respective reviews of Jacob's The Logic of the Living. For Canguilhem this was an opportunity to reaffirm the creativity of life in the living individual, which is not a thing to be evaluated, but the source of values. For Foucault, drawing on Jacob's work, this was the opportunity to develop a transformed account of valuation by posing biopower as the DNA of society. Despite their disagreements, the paper examines these three authors as different iterations of a historical epistemology attuned to errancy, error, and experimentation.

  9. How phenotypic plasticity made its way into molecular biology

    Indian Academy of Sciences (India)

    Michel Morange

    2009-10-01

    Phenotypic plasticity has been fashionable in recent years. It has never been absent from the studies of evolutionary biologists, although the availability of stable animal models has limited its role. Although opposed by the reductionist and deterministic approach of molecular biology, phenotypic plasticity has nevertheless recently made its way into this discipline, in particular through the limits of the molecular description. Its resurrection has been triggered by a small group of theoreticians, the rise of epigenetic descriptions and the publicized discovery of stem cell plasticity. The notion of phenotypic plasticity remains vague. History shows that too strong a belief in plasticity can be an obstacle to the development of biology. Two important questions are still pending: the link between the different forms of plasticity present at different levels of organization, and the relation, if any, between the modular organization of organisms and phenotypic plasticity. Future research will help to discriminate between possible and actual mechanisms of phenotypic plasticity, and to give phenotypic plasticity its real place in the living world.

  10. The role of molecular biology in veterinary parasitology.

    Science.gov (United States)

    Prichard, R; Tait, A

    2001-07-12

    The tools of molecular biology are increasingly relevant to veterinary parasitology. The sequencing of the complete genomes of Caenorhabditis elegans and other helminths and protozoa is allowing great advances in studying the biology, and improving diagnosis and control of parasites. Unique DNA sequences provide very high levels of specificity for the diagnosis and identification of parasite species and strains, and PCR allows extremely high levels of sensitivity. New techniques, such as the use of uniquely designed molecular beacons and DNA microarrays will eventually allow rapid screening for specific parasite genotypes and assist in diagnostic and epidemiological studies of veterinary parasites. The ability to use genome data to clone and sequence genes which when expressed will provide antigens for vaccine screening and receptors and enzymes for mechanism-based chemotherapy screening will increase our options for parasite control. In addition, DNA vaccines can have desirable characteristics, such as sustained stimulation of the host immune system compared with protein based vaccines. One of the greatest threats to parasite control has been the development of drug resistance in parasites. Our knowledge of the basis of drug resistance and our ability to monitor its development with highly sensitive and specific DNA-based assays for 'resistance'-alleles will help maintain the effectiveness of existing antiparasitic drugs and provide hope that we can maintain control of parasitic disease outbreaks.

  11. Chemical biology drug sensitivity screen identifies sunitinib as synergistic agent with disulfiram in prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Kirsi Ketola

    Full Text Available BACKGROUND: Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects. METHODS AND FINDINGS: In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression. CONCLUSIONS: Taken together, our results propose novel combinatorial approaches to inhibit

  12. Chemical Biology Drug Sensitivity Screen Identifies Sunitinib as Synergistic Agent with Disulfiram in Prostate Cancer Cells

    Science.gov (United States)

    Ketola, Kirsi; Kallioniemi, Olli; Iljin, Kristiina

    2012-01-01

    Background Current treatment options for castration- and treatment-resistant prostate cancer are limited and novel approaches are desperately needed. Our recent results from a systematic chemical biology sensitivity screen covering most known drugs and drug-like molecules indicated that aldehyde dehydrogenase inhibitor disulfiram is one of the most potent cancer-specific inhibitors of prostate cancer cell growth, including TMPRSS2-ERG fusion positive cancers. However, the results revealed that disulfiram alone does not block tumor growth in vivo nor induce apoptosis in vitro, indicating that combinatorial approaches may be required to enhance the anti-neoplastic effects. Methods and Findings In this study, we utilized a chemical biology drug sensitivity screen to explore disulfiram mechanistic details and to identify compounds potentiating the effect of disulfiram in TMPRSS2-ERG fusion positive prostate cancer cells. In total, 3357 compounds including current chemotherapeutic agents as well as drug-like small molecular compounds were screened alone and in combination with disulfiram. Interestingly, the results indicated that androgenic and antioxidative compounds antagonized disulfiram effect whereas inhibitors of receptor tyrosine kinase, proteasome, topoisomerase II, glucosylceramide synthase or cell cycle were among compounds sensitizing prostate cancer cells to disulfiram. The combination of disulfiram and an antiangiogenic agent sunitinib was studied in more detail, since both are already in clinical use in humans. Disulfiram-sunitinib combination induced apoptosis and reduced androgen receptor protein expression more than either of the compounds alone. Moreover, combinatorial exposure reduced metastatic characteristics such as cell migration and 3D cell invasion as well as induced epithelial differentiation shown as elevated E-cadherin expression. Conclusions Taken together, our results propose novel combinatorial approaches to inhibit prostate cancer cell

  13. 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

  14. Holism and life manifestations: molecular and space-time biology.

    Science.gov (United States)

    Krecek, J

    2010-01-01

    Appeals of philosophers to look for new concepts in sciences are being met with a weak response. Limited attention is paid to the relation between synthetic and analytic approach in solving problems of biology. An attempt is presented to open a discussion on a possible role of holism. The term "life manifestations" is used in accordance with phenomenology. Multicellular creatures maintain milieu intérieur to keep an aqueous milieu intracellulair in order to transform the energy of nutrients into the form utilizable for driving cellular life manifestations. Milieu intérieur enables to integrate this kind of manifestations into life manifestations of the whole multicellular creatures. The integration depends on a uniqueness and uniformity of the genome of cells, on their mutual recognition and adherence. The processes of ontogenetic development represent the natural mode of integration of cellular life manifestations. Functional systems of multicellular creatures are being established by organization of integrable cells using a wide range of developmental processes. Starting from the zygote division the new being displays all properties of a whole creature, although its life manifestations vary. Therefore, the whole organism is not only more than its parts, as supposed by holism, but also more than developmental stages of its life manifestations. Implicitly, the units of whole multicellular creature are rather molecular and developmental events than the cells per se. Holism, taking in mind the existence of molecular and space-time biology, could become a guide in looking for a new mode of the combination of analytical and synthetic reasoning in biology.

  15. The current state of molecular cytogenetics in cancer diagnosis.

    Science.gov (United States)

    Liehr, Thomas; Othman, Moneeb A K; Rittscher, Katharina; Alhourani, Eyad

    2015-04-01

    Cytogenetics and molecular cytogenetics are and will continue to be indispensable tools in cancer diagnostics. Leukemia and lymphoma diagnostics are still emphases of routine (molecular) cytogenetics and corresponding studies of solid tumors gain more and more prominence. Here, first a historical perspective of molecular tumor cytogenetics is provided, which is followed by the basic principles of the fluorescence in situ hybridization (FISH) approach. Finally the current state of molecular cytogenetics in cancer diagnostics is discussed. Nowadays routine diagnostics includes basic FISH approaches rather than multicolor-FISH. The latter together with modern high-throughput methods have their impact on research to identify new tumor-associated genomic regions.

  16. Transmission electron microscopy in molecular structural biology: A historical survey.

    Science.gov (United States)

    Harris, J Robin

    2015-09-01

    In this personal, historic account of macromolecular transmission electron microscopy (TEM), published data from the 1940s through to recent times is surveyed, within the context of the remarkable progress that has been achieved during this time period. The evolution of present day molecular structural biology is described in relation to the associated biological disciplines. The contribution of numerous electron microscope pioneers to the development of the subject is discussed. The principal techniques for TEM specimen preparation, thin sectioning, metal shadowing, negative staining and plunge-freezing (vitrification) of thin aqueous samples are described, with a selection of published images to emphasise the virtues of each method. The development of digital image analysis and 3D reconstruction is described in detail as applied to electron crystallography and reconstructions from helical structures, 2D membrane crystals as well as single particle 3D reconstruction of icosahedral viruses and macromolecules. The on-going development of new software, algorithms and approaches is highlighted before specific examples of the historical progress of the structural biology of proteins and viruses are presented.

  17. Embryonic stem cell biology: insights from molecular imaging.

    Science.gov (United States)

    Sallam, Karim; Wu, Joseph C

    2010-01-01

    Embryonic stem (ES) cells have therapeutic potential in disorders of cellular loss such as myocardial infarction, type I diabetes and neurodegenerative disorders. ES cell biology in living subjects was largely poorly understood until incorporation of molecular imaging into the field. Reporter gene imaging works by integrating a reporter gene into ES cells and using a reporter probe to induce a signal detectable by normal imaging modalities. Reporter gene imaging allows for longitudinal tracking of ES cells within the same host for a prolonged period of time. This has advantages over postmortem immunohistochemistry and traditional imaging modalities. The advantages include expression of reporter gene is limited to viable cells, expression is conserved between generations of dividing cells, and expression can be linked to a specific population of cells. These advantages were especially useful in studying a dynamic cell population such as ES cells and proved useful in elucidating the biology of ES cells. Reporter gene imaging identified poor integration of differentiated ES cells transplanted into host tissue as well as delayed donor cell death as reasons for poor long-term survival in vivo. This imaging technology also confirmed that ES cells indeed have immunogenic properties that factor into cell survival and differentiation. Finally, reporter gene imaging improved our understanding of the neoplastic risk of undifferentiated ES cells in forming teratomas. Despite such advances, much remains to be understood about ES cell biology to translate this technology to the bedside, and reporter gene imaging will certainly play a key role in formulating this understanding.

  18. Molecular biology of insect sodium channels and pyrethroid resistance.

    Science.gov (United States)

    Dong, Ke; Du, Yuzhe; Rinkevich, Frank; Nomura, Yoshiko; Xu, Peng; Wang, Lingxin; Silver, Kristopher; Zhorov, Boris S

    2014-07-01

    Voltage-gated sodium channels are essential for the initiation and propagation of the action potential in neurons and other excitable cells. Because of their critical roles in electrical signaling, sodium channels are targets of a variety of naturally occurring and synthetic neurotoxins, including several classes of insecticides. This review is intended to provide an update on the molecular biology of insect sodium channels and the molecular mechanism of pyrethroid resistance. Although mammalian and insect sodium channels share fundamental topological and functional properties, most insect species carry only one sodium channel gene, compared to multiple sodium channel genes found in each mammalian species. Recent studies showed that two posttranscriptional mechanisms, alternative splicing and RNA editing, are involved in generating functional diversity of sodium channels in insects. More than 50 sodium channel mutations have been identified to be responsible for or associated with knockdown resistance (kdr) to pyrethroids in various arthropod pests and disease vectors. Elucidation of molecular mechanism of kdr led to the identification of dual receptor sites of pyrethroids on insect sodium channels. Many of the kdr mutations appear to be located within or close to the two receptor sites. The accumulating knowledge of insect sodium channels and their interactions with insecticides provides a foundation for understanding the neurophysiology of sodium channels in vivo and the development of new and safer insecticides for effective control of arthropod pests and human disease vectors.

  19. 乳腺癌的分子分型%Molecular classification of breast cancer

    Institute of Scientific and Technical Information of China (English)

    张百红; 岳红云

    2014-01-01

    乳腺癌是一种分子水平异质性很高的疾病,分子分型可为乳腺癌的个体化治疗提供一个新视野.在分子病理学、分子生物学和系统生物学指导下,乳腺癌经历了4类分型、70种和21种基因蛋白谱以及基因组整合分类等不同分型.这些分型将为乳腺癌的精确治疗提供指导.%Breast cancer is a group of heterogeneous diseases.Molecular portraits provide a new insight for personalized cancer management in breast cancer.According to the molecular pathology,molecular biology and system biology,breast cancer goes through different typing methods,including four subclasses,geneexpression signature and integrated genomic classification.These major subtypes of breast cancer may provide guidance for precise therapeutics.

  20. Molecular cytogenetics: recent developments and applications in cancer.

    Science.gov (United States)

    Das, K; Tan, P

    2013-10-01

    Aneuploidy or alteration in chromosome numbers is a characteristic feature in cancer that is generally a consequence of defective chromosome segregation during cell division. Molecular cytogenetic analyses have conferred substantial evidence with regards to the chromosomal architectures in cancer. Most importantly, the fluorescence in situ hybridization (FISH) technique that plays a leading role in diagnostic pathology for its single-cell analysis has provided crucial information regarding genomic variations in malignant cells. Further development of molecular cytogenetic methodologies such as chromosome specific FISH karyotyping and comparative genomic hybridization have also helped in the detection of cryptic genetic changes in cancer. But, the recent advancement of high throughput sequencing technologies have provided a more comprehensive genomic analyses resulting in novel chromosome rearrangements, somatic mutations as well as identification of fusion genes leading to new therapeutic targets. This review highlights the application of early molecular cytogenetics and the recent high throughput genomic approaches in characterizing various cancers and their invaluable support in cancer therapeutics.

  1. Sphingosine kinase 1 is a relevant molecular target in gastric cancer

    DEFF Research Database (Denmark)

    Fuereder, Thorsten; Hoeflmayer, Doris; Jaeger-Lansky, Agnes

    2011-01-01

    Sphingosine kinase 1 (Sphk1), a lipid kinase implicated in cell transformation and tumor growth, is overexpressed in gastric cancer and is linked with a poor prognosis. The biological relevance of Sphk1 expression in gastric cancer is unclear. Here, we studied the functional significance of Sphk1...... as a novel molecular target for gastric cancer by using an antisense oligonucleotide approach in vitro and in vivo. Gastric cancer cell lines (MKN28 and N87) were treated with Sphk1 with locked nucleic acid-antisense oligonucleotides (LNA-ASO). Sphk1 target regulation, cell growth, and apoptosis were...... assessed for single-agent Sphk1 LNA-ASO and for combinations with doxorubicin. Athymic nude mice xenografted with gastric cancer cells were treated with Sphk1 LNA and assessed for tumor growth and Sphk1 target regulation, in vivo. In vitro, nanomolar concentrations of Sphk1 LNA-ASO induced an approximately...

  2. Molecular Mechanism by Which Retinoids Prevent Breast Cancer Development

    Science.gov (United States)

    2007-06-01

    clinicians to conquer this disease is to prevent the incidence, detect early and treat breast cancer with effective therapy resulting in long overall... biological functions such as embryogenesis, growth, differentiation, vision and reproduction (3-6). Retinoids also contain anti- proliferative...and are currently available to treat psoriasis , acne, photoaging, actinic keratosis or cancers such as acute promelocytic leukemia, cutaneous T-cell

  3. 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.

  4. Basic evidence of molecular targeted therapy for oral cancer and salivary gland cancer.

    NARCIS (Netherlands)

    Hamakawa, H.; Nakashiro, K.; Sumida, T.; Shintani, S.; Myers, J.N.; Takes, R.P.; Rinaldo, A.; Ferlito, A.

    2008-01-01

    BACKGROUND: Recently, attention has been focused on molecular targeted cancer therapy in various tumors. Although there is no single consistent molecular target specific for oral squamous cell carcinoma (OSCC) and salivary gland cancer (SGC), there are a number of promising candidate proteins. The a

  5. Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology.

    Science.gov (United States)

    Chiba, Tetsuhiro; Iwama, Atsushi; Yokosuka, Osamu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related death worldwide. Despite advances in its diagnosis and treatment, the prognosis of patients with advanced HCC remains unfavorable. Recent advances in stem cell biology and associated technologies have enabled the identification of minor components of tumorigenic cells, termed cancer stem cells (CSC) or tumor-initiating cells, in cancers such as HCC. Furthermore, because CSC play a central role in tumor development, metastasis and recurrence, they are considered to be a therapeutic target in cancer treatment. Hepatic CSC have been successfully identified using functional and cell surface markers. The analysis of purified hepatic CSC has revealed the molecular machinery and signaling pathways involved in their maintenance. In addition, epigenetic transcriptional regulation has been shown to be important in the development and maintenance of CSC. Although inhibitors of CSC show promise as CSC-targeting drugs, novel therapeutic approaches for the eradication of CSC are yet to be established. In this review, we describe recent progress in hepatic CSC research and provide a perspective on the available therapeutic approaches based on stem cell biology.

  6. [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.

  7. Implementation and Assessment of a Molecular Biology and Bioinformatics Undergraduate Degree Program

    Science.gov (United States)

    Pham, Daphne Q. -D.; Higgs, David C.; Statham, Anne; Schleiter, Mary Kay

    2008-01-01

    The Department of Biological Sciences at the University of Wisconsin-Parkside has developed and implemented an innovative, multidisciplinary undergraduate curriculum in Molecular Biology and Bioinformatics (MBB). The objective of the MBB program is to give students a hands-on facility with molecular biology theories and laboratory techniques, an…

  8. A Molecular Epidemiologic Case-Case Study of Prostate Cancer

    Science.gov (United States)

    2002-03-01

    Receptor Polymorphism and Prostate Cancer Risk 1 Sara S. Strom 2, Qiang Zhang, Yun Gu, Margaret R. Spitz, Peter T. Scardino 3, Christopher J. Logothetis...Taylor, J. A. Vitamin D receptor polymorphisms and prostate cancer. Molecular Carcinogenesis, 27: 18-23, 2000. 6. Ma, J., Stampfer , M. J., Gann, P. H...Margaret R. Spitz, Richard J. Babaian, Christopher Logothetis, Sara S. Strom, University of Texas M.D. Anderson Cancer Center, Houston, TX; The University

  9. Traffic phenomena in biology: from molecular motors to organisms

    CERN Document Server

    Chowdhury, D; Nishinari, K; Chowdhury, Debashish; Schadschneider, Andreas; Nishinari, Katsuhiro

    2007-01-01

    Traffic-like collective movements are observed at almost all levels of biological systems. Molecular motor proteins like, for example, kinesin and dynein, which are the vehicles of almost all intra-cellular transport in eukayotic cells, sometimes encounter traffic jam that manifests as a disease of the organism. Similarly, traffic jam of collagenase MMP-1, which moves on the collagen fibrils of the extracellular matrix of vertebrates, has also been observed in recent experiments. Traffic-like movements of social insects like ants and termites on trails are, perhaps, more familiar in our everyday life. Experimental, theoretical and computational investigations in the last few years have led to a deeper understanding of the generic or common physical principles involved in these phenomena. In particular, some of the methods of non-equilibrium statistical mechanics, pioneered almost a hundred years ago by Einstein, Langevin and others, turned out to be powerful theoretical tools for quantitative analysis of mode...

  10. Biomarkers of Aging: From Function to Molecular Biology.

    Science.gov (United States)

    Wagner, Karl-Heinz; Cameron-Smith, David; Wessner, Barbara; Franzke, Bernhard

    2016-06-02

    Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

  11. Molecular biological characterization of equine surfactant protein A.

    Science.gov (United States)

    Hospes, R; Hospes, B I L; Reiss, I; Bostedt, H; Gortner, L

    2002-12-01

    In the following, we describe the isolation and sequencing of the equine surfactant protein A (Sp-A) as found in both the cDNA and the genomic DNA. We found a length of the cDNA sequence of 747 bp (base pairs), in translation into amino acids of 248. Compared with the known molecular biological facts about Sp-A in other species, the cDNA sequence obtained showed highest homology with that of sheep (85.01%). The genomic DNA of equine Sp-A, as in other species, includes three introns. There were no hints for the existence of two different Sp-A genes. These results should form the basis for a better understanding of respiratory failure in foals and adult horses, and also lead to further studies on this item.

  12. Obstructive renal injury: from fluid mechanics to molecular cell biology.

    Science.gov (United States)

    Ucero, Alvaro C; Gonçalves, Sara; Benito-Martin, Alberto; Santamaría, Beatriz; Ramos, Adrian M; Berzal, Sergio; Ruiz-Ortega, Marta; Egido, Jesus; Ortiz, Alberto

    2010-04-22

    Urinary tract obstruction is a frequent cause of renal impairment. The physiopathology of obstructive nephropathy has long been viewed as a mere mechanical problem. However, recent advances in cell and systems biology have disclosed a complex physiopathology involving a high number of molecular mediators of injury that lead to cellular processes of apoptotic cell death, cell injury leading to inflammation and resultant fibrosis. Functional studies in animal models of ureteral obstruction using a variety of techniques that include genetically modified animals have disclosed an important role for the renin-angiotensin system, transforming growth factor-β1 (TGF-β1) and other mediators of inflammation in this process. In addition, high throughput techniques such as proteomics and transcriptomics have identified potential biomarkers that may guide clinical decision-making.

  13. Escherichia coli and the French School of Molecular Biology.

    Science.gov (United States)

    Ullmann, Agnes

    2010-09-01

    André Lwoff, Jacques Monod, and François Jacob, the leaders of the French school of molecular biology, greatly contributed between 1937 and 1965 to its development and triumph. The main discovery of Lwoff was the elucidation of the mechanism of bacteriophage induction, the phenomenon of lysogeny, that led to the model of genetic regulation uncovered later by Jacob and Monod. Working on bacterial growth, Monod discovered in 1941 the phenomenon of diauxy and uncovered the nature of enzyme induction. By combining genetic and biochemical approaches, Monod brought to light the structure and functions of the Escherichia coli lactose system, comprising the genes necessary for lactose metabolism, i.e., β-galactosidase and lactose permease, a pump responsible for accumulation of galactosides into the cells. An additional genetic factor (the i gene) determines the inducibility and constitutivity of enzyme synthesis. Around the same time, François Jacob and Elie Wollman dissected the main events of bacterial conjugation that enabled them to construct a map of the E. coli chromosome and to demonstrate its circularity. The genetic analysis of the lactose system led Monod and Jacob to elucidate the mechanism of the regulation of gene expression and to propose the operon model: a unit of coordinate transcription. One of the new concepts that emerged from the operon model was messenger RNA. In 1963, Monod developed one of the most elegant concepts of molecular biology, the theory of allostery. In 1965, Lwoff, Monod and Jacob were awarded the Nobel Prize in Physiology or Medicine.

  14. Ecology meets cancer biology: the cancer swamp promotes the lethal cancer phenotype.

    Science.gov (United States)

    Amend, Sarah R; Pienta, Kenneth J

    2015-01-01

    As they grow, tumors fundamentally alter their microenvironment, disrupting the homeostasis of the host organ and eventually the patient as a whole. Lethality is the ultimate result of deregulated cell signaling and regulatory mechanisms as well as inappropriate host cell recruitment and activity that lead to the death of the patient. These processes have striking parallels to the framework of ecological biology: multiple interacting ecosystems (organ systems) within a larger biosphere (body), alterations in species stoichiometry (host cell types), resource cycling (cellular metabolism and cell-cell signaling), and ecosystem collapse (organ failure and death). In particular, as cancer cells generate their own niche within the tumor ecosystem, ecological engineering and autoeutrophication displace normal cell function and result in the creation of a hypoxic, acidic, and nutrient-poor environment. This "cancer swamp" has genetic and epigenetic effects at the local ecosystem level to promote metastasis and at the systemic host level to induce cytokine-mediated lethal syndromes, a major cause of death of cancer patients.

  15. New generation of breast cancer clinical trials implementing molecular profiling

    Institute of Scientific and Technical Information of China (English)

    Dimitrios Zardavas; Martine Piccart-Gebhart

    2016-01-01

    The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as pre-screening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i) longitudinal cohort studies that implement (or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials.

  16. Natural biology and management of nonmuscle invasive bladder cancer

    DEFF Research Database (Denmark)

    Scarpato, Kristen R; Tyson, Mark D; Clark, Peter E

    2016-01-01

    PURPOSE OF REVIEW: This article reviews the natural biology of noninvasive bladder cancer and its management strategies while summarizing the most recent advances in the field. RECENT FINDINGS: Nonmuscle invasive bladder cancer (NMIBC) has a tendency to recur and progress. Risk stratification has...... treatment, especially in refractory high-risk cases, include the addition of intravesical hyperthermia, combination and sequential therapy with existing agents and the use of novel agents such as mycobacterial cell wall extract. New data are emerging regarding the potential role of active surveillance...... in low-risk patients. SUMMARY: NMIBC represents a variety of disease states and continues to pose management challenges. As our understanding of tumor biology improves and technology advances, achieving better outcomes through individualized care may be possible....

  17. 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.

  18. Molecular Biology and Infection of Hepatitis E Virus

    Directory of Open Access Journals (Sweden)

    Yuchen Nan

    2016-09-01

    Full Text Available Hepatitis E virus (HEV is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotype 3 and 4 are zoonotic, whereas those from genotype 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.

  19. Molecular Biology and Infection of Hepatitis E Virus

    Science.gov (United States)

    Nan, Yuchen; Zhang, Yan-Jin

    2016-01-01

    Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus. PMID:27656178

  20. 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.

  1. Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

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    Bishnu P. Joshi

    2010-06-01

    Full Text Available Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research.

  2. Molecular codes in biological and chemical reaction networks.

    Science.gov (United States)

    Görlich, Dennis; Dittrich, Peter

    2013-01-01

    Shannon's theory of communication has been very successfully applied for the analysis of biological information. However, the theory neglects semantic and pragmatic aspects and thus cannot directly be applied to distinguish between (bio-) chemical systems able to process "meaningful" information from those that do not. Here, we present a formal method to assess a system's semantic capacity by analyzing a reaction network's capability to implement molecular codes. We analyzed models of chemical systems (martian atmosphere chemistry and various combustion chemistries), biochemical systems (gene expression, gene translation, and phosphorylation signaling cascades), an artificial chemistry, and random reaction networks. Our study suggests that different chemical systems possess different semantic capacities. No semantic capacity was found in the model of the martian atmosphere chemistry, the studied combustion chemistries, and highly connected random networks, i.e. with these chemistries molecular codes cannot be implemented. High semantic capacity was found in the studied biochemical systems and in random reaction networks where the number of second order reactions is twice the number of species. We conclude that our approach can be applied to evaluate the information processing capabilities of a chemical system and may thus be a useful tool to understand the origin and evolution of meaningful information, e.g. in the context of the origin of life.

  3. Molecularly Imprinted Polymers for 5-Fluorouracil Release in Biological Fluids

    Directory of Open Access Journals (Sweden)

    Franco Alhaique

    2007-04-01

    Full Text Available The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs as a controlled release device for 5-fluorouracil (5-FU in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs. MIPs were synthesized using methacrylic acid (MAA as functional monomer and ethylene glycol dimethacrylate (EGDMA as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic and aqueous media was evaluated. An in vitro release study was performed both in gastrointestinal and in plasma simulating fluids. The imprinted polymers bound much more 5-Fu than the corresponding non-imprinted ones and showed a controlled/sustained drug release, with MIPs release rate being indeed much more sustained than that obtained from NIPs. These polymers represent a potential valid system for drug delivery and this study indicates that the selective binding characteristic of molecularly imprinted polymers is promising for the preparation of novel controlled release drug dosage form.

  4. Molecularly imprinted polymers for 5-fluorouracil release in biological fluids.

    Science.gov (United States)

    Puoci, Francesco; Iemma, Francesca; Cirillo, Giuseppe; Picci, Nevio; Matricardi, Pietro; Alhaiqu, Franco

    2007-04-18

    The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs) as a controlled release device for 5-fluorouracil (5-FU) in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs). MIPs were synthesized using methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic and aqueous media was evaluated. An in vitro release study was performed both in gastrointestinal and in plasma simulating fluids. The imprinted polymers bound much more 5-Fu than the corresponding non-imprinted ones and showed a controlled/sustained drug release, with MIPs release rate being indeed much more sustained than that obtained from NIPs. These polymers represent a potential valid system for drug delivery and this study indicates that the selective binding characteristic of molecularly imprinted polymers is promising for the preparation of novel controlled release drug dosage form.

  5. Investigation of the molecular relationship between breast cancer and obesity by candidate gene prioritization methods

    Directory of Open Access Journals (Sweden)

    Saba Garshasbi

    2015-10-01

    Full Text Available Background: Cancer and obesity are two major public health concerns. More than 12 million cases of cancer are reported annually. Many reports confirmed obesity as a risk factor for cancer. The molecular relationship between obesity and breast cancer has not been clear yet. The purpose of this study was to investigate priorities of effective genes in the molecular relationship between obesity and breast cancer. Methods: In this study, computer simulation method was used for prioritizing the genes that involved in the molecular links between obesity and breast cancer in laboratory of systems biology and bioinformatics (LBB, Tehran University, Tehran, Iran, from March to July 2014. In this study, ENDEAVOUR software was used for prioritizing the genes and integrating multiple data sources was used for data analysis. Training genes were selected from effective genes in obesity and/or breast cancer. Two groups of candidate genes were selected. The first group was included the existential genes in 5 common region chromosomes (between obesity and breast cancer and the second group was included the results of genes microarray data analysis of research Creighton, et al (In 2012 on patients with breast cancer. The microarray data were analyzed with GER2 software (R online software on GEO website. Finally, both training and candidate genes were entered in ENDEAVOUR software package. Results: The candidate genes were prioritized to four style and five genes in ten of the first priorities were repeated twice. In other word, the outcome of prioritizing of 72 genes (Product of microarray data analysis and genes of 5 common chromosome regions (Between obesity and breast cancer showed, 5 genes (TNFRSF10B, F2, IGFALS, NTRK3 and HSP90B1 were the priorities in the molecular connection between obesity and breast cancer. Conclusion: There are some common genes between breast cancer and obesity. So, molecular relationship is confirmed. In this study the possible effect

  6. Cold Spring Harbor symposia on quantitative biology: Volume 51, Molecular biology of Homo sapiens

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    Thirteen years marked the time between the discovery of the double helix in 1953 and the elucidation of the genetic code in 1966. A similar interval has now passed since the development by Cohen and Boyer of a simple procedure for the cloning of selective DNA fragments. The scientific advances made possible by the subsequent modification and elaboration of these original cloning procedures now amaze, stimulate, and increasingly often overwhelm us. Facts that until recently were virtually unobtainable now flow forth almost effortlessly. Most excitingly, the frenetic pace of these new discoveries, instead of marking the impending end of a glorious moment of learning, give every indication of opening up scientific frontiers that will take hundreds if not thousands of years to explore thoroughly. This new era of enlightenment is nowhere more apparent than in our newfound ability to study ourselves at the molecular level. This volume is the first of two collections of papers submitted by the contributors to the Cold Spring Harbor symposia on quantitative biology for 1986 - molecular biology of Homo sapiens. Contained in this collection are 80 papers grouped into sessions entitled Human Gene Map, Genetic Diagnosis, Human Evolution, and Drugs Made Off Human Genes.

  7. Novel approaches for the molecular classification of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Robert H. Getzenberg

    2010-01-01

    @@ Among the urologic cancers, prostate cancer is by far the most common, and it appears to have the potential to affect almost all men throughout the world as they age. A number of studies have shown that many men with prostate cancer will not die from their disease, but rather with the disease but from other causes. These men have a form of prostate cancer that is de-scribed as "very low risk" and has often been called indolent. There are however a group of men that have a form of prostate cancer that is much more aggressive and life threatening. Unlike other cancer types, we have few tools to provide for the molecular classification of prostate cancer.

  8. Molecular and neuroendocrine mechanisms of cancer cachexia.

    Science.gov (United States)

    Mendes, Maria Carolina S; Pimentel, Gustavo D; Costa, Felipe O; Carvalheira, José B C

    2015-09-01

    Cancer and its morbidities, such as cancer cachexia, constitute a major public health problem. Although cancer cachexia has afflicted humanity for centuries, its underlying multifactorial and complex physiopathology has hindered the understanding of its mechanism. During the last few decades we have witnessed a dramatic increase in the understanding of cancer cachexia pathophysiology. Anorexia and muscle and adipose tissue wasting are the main features of cancer cachexia. These apparently independent symptoms have humoral factors secreted by the tumor as a common cause. Importantly, the hypothalamus has emerged as an organ that senses the peripheral signals emanating from the tumoral environment, and not only elicits anorexia but also contributes to the development of muscle and adipose tissue loss. Herein, we review the roles of factors secreted by the tumor and its effects on the hypothalamus, muscle and adipose tissue, as well as highlighting the key targets that are being exploited for cancer cachexia treatment.

  9. Ultrasound for molecular imaging and therapy in cancer

    OpenAIRE

    Kaneko, Osamu F; Willmann, Jürgen K.

    2012-01-01

    Over the past decade, molecularly-targeted contrast enhanced ultrasound (ultrasound molecular imaging) has attracted significant attention in preclinical research of cancer diagnostic and therapy. Potential applications for ultrasound molecular imaging run the gamut from early detection and characterization of malignancies to monitoring treatment responses and guiding therapies. There may also be a role for ultrasound contrast agents for improved delivery of chemotherapeutic drugs and gene th...

  10. Molecular Concordance Between Primary Breast Cancer and Matched Metastases

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Thomassen, Mads;

    2016-01-01

    . The purpose of this review is to illuminate the extent of cancer genome evolution through disease progression and the degree of molecular concordance between primary breast cancers and matched metastases. We present an overview of the most prominent studies investigating the expression of endocrine receptors......Clinical management of breast cancer is increasingly personalized and based on molecular profiling. Often, primary tumors are used as proxies for systemic disease at the time of recurrence. However, recent studies have revealed substantial discordances between primary tumors and metastases, both......, transcriptomics, and genome aberrations in primary tumors and metastases. In conclusion, biopsy of metastatic lesions at recurrence of breast cancer is encouraged to provide optimal treatment of the disease. Furthermore, molecular profiling of metastatic tissue provides invaluable mechanistic insight...

  11. Deciphering the Molecular Mechanisms of Breast Cancer

    Science.gov (United States)

    2005-03-01

    BRCA1 and BRCA2, by a Signalosome-like Subunit and its Role in DNA Repair. Molecular Cell 12; 1087-1099 (2003). Presentations/Abstracts...BRCA1 and BRCA2, by a Signalosome-like Subunit and its Role in DNA Repair. Molecular Cell 12; 1087-1099. APPENDICIES: CURRICULUM VITAE...Oncogenesis Program Member, Faculty Recruitment Committee Periodic Manuscript Reviews: Cell, Science, Molecular Cell , Molecular and Cellular

  12. Anatomical and molecular imaging of skin cancer

    OpenAIRE

    Cai, Weibo

    2008-01-01

    Hao Hong1, Jiangtao Sun1, Weibo Cai1,21Departments of Radiology and Medical Physics, School of Medicine and Public Health, University of Wisconsin – Madison, Madison, Wisconsin, USA; 2University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin, USAAbstract: Skin cancer is the most common form of cancer types. It is generally divided into two categories: melanoma (∼5%) and nonmelanoma (∼95%), which can be further categorized into basal cell...

  13. 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

  14. The Molecular Biology Toolkit (MBT: a modular platform for developing molecular visualization applications

    Directory of Open Access Journals (Sweden)

    Zhang Qing

    2005-02-01

    Full Text Available Abstract Background The large amount of data that are currently produced in the biological sciences can no longer be explored and visualized efficiently with traditional, specialized software. Instead, new capabilities are needed that offer flexibility, rapid application development and deployment as standalone applications or available through the Web. Results We describe a new software toolkit – the Molecular Biology Toolkit (MBT; http://mbt.sdsc.edu – that enables fast development of applications for protein analysis and visualization. The toolkit is written in Java, thus offering platform-independence and Internet delivery capabilities. Several applications of the toolkit are introduced to illustrate the functionality that can be achieved. Conclusions The MBT provides a well-organized assortment of core classes that provide a uniform data model for the description of biological structures and automate most common tasks associated with the development of applications in the molecular sciences (data loading, derivation of typical structural information, visualization of sequence and standard structural entities.

  15. Mathematical biology modules based on modern molecular biology and modern discrete mathematics.

    Science.gov (United States)

    Robeva, Raina; Davies, Robin; Hodge, Terrell; Enyedi, Alexander

    2010-01-01

    We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network.

  16. Molecular biology of anal squamous cell carcinoma: implications for future research and clinical intervention.

    Science.gov (United States)

    Bernardi, Maria-Pia; Ngan, Samuel Y; Michael, Michael; Lynch, A Craig; Heriot, Alexander G; Ramsay, Robert G; Phillips, Wayne A

    2015-12-01

    Anal squamous cell carcinoma is a human papillomavirus-related disease, in which no substantial advances in treatment have been made in over 40 years, especially for those patients who develop disease relapse and for whom no surgical options exist. HPV can evade the immune system and its role in disease progression can be exploited in novel immunotherapy platforms. Although several studies have investigated the expression and inactivation (through loss of heterozygosity) of tumour suppressor genes in the pathways to cancer, no clinically valuable biomarkers have emerged. Regulators of apoptosis, including survivin, and agents targeting the PI3K/AKT pathway, offer opportunities for targeted therapy, although robust data are scarce. Additionally, antibody therapy targeting EGFR may prove effective, although its safety profile in combination with standard chemoradiotherapy has proven to be suboptimal. Finally, progress in the treatment of anal cancer has remained stagnant due to a lack of preclinical models, including cell lines and mouse models. In this Review, we discuss the molecular biology of anal squamous cell carcinoma, clinical trials in progress, and implications for novel therapeutic targets. Future work should focus on preclinical models to provide a resource for investigation of new molecular pathways and for testing novel targets.

  17. Molecular Genetics Techniques to Develop New Treatments for Brain Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Fox, Jacob; Fathallan-Shaykh, Hassan

    2006-09-22

    The objectives of this report are: (1) to devise novel molecular gene therapies for malignant brain tumors, (2) advance our understanding of the immune system in the central nervous system; and (3) apply genomics to find molecular probes to diagnose brain tumors, predict prognosis, biological behavior and their response to treatment.

  18. New Strategies on Molecular Biology Applied to Microbial Systematics

    Directory of Open Access Journals (Sweden)

    HÖFLING José F.

    1997-01-01

    Full Text Available Systematics is the study of diversity of the organisms and their relationships comprising classification, nomenclature and identification. The term classification or taxonomy means the arrangement of the organisms in groups (rate and the nomenclature is the attribution of correct international scientific names to organisms and identification is the inclusion of unknown strains in groups derived from classification. Therefore, classification for a stable nomenclature and a perfect identification are required previously. The beginning of the new bacterial systematics era can be remembered by the introduction and application of new taxonomic concepts and techniques, from the 50?s and 60?s. Important progress were achieved using numerical taxonomy and molecular taxonomy. Molecular taxonomy, brought into effect after the emergence of the Molecular Biology resources, provided knowledge that comprises systematics of bacteria, in which occurs great evolutionary interest, or where is observed the necessity of eliminating any environmental interference. When you study the composition and disposition of nucleotides in certain portions of the genetic material, you study searching their genome, much less susceptible to environmental alterations than proteins, codified based on it. In the molecular taxonomy, you can research both DNA and RNA, and the main techniques that have been used in the systematics comprise the build of restriction maps, DNA-DNA hybridization, DNA-RNA hybridization, sequencing of DNA sequencing of sub-units 16S and 23S of rRNA, RAPD, RFLP, PFGE etc. Techniques such as base sequencing, though they are extremely sensible and greatly precise, are relatively onerous and impracticable to the great majority of the bacterial taxonomy laboratories. Several specialized techniques have been applied to taxonomic studies of microorganisms. In the last years, these have included preliminary electrophoretic analysis of soluble proteins and isoenzymes

  19. The 2015 Nucleic Acids Research Database Issue and molecular biology database collection.

    Science.gov (United States)

    Galperin, Michael Y; Rigden, Daniel J; Fernández-Suárez, Xosé M

    2015-01-01

    The 2015 Nucleic Acids Research Database Issue contains 172 papers that include descriptions of 56 new molecular biology databases, and updates on 115 databases whose descriptions have been previously published in NAR or other journals. Following the classification that has been introduced last year in order to simplify navigation of the entire issue, these articles are divided into eight subject categories. This year's highlights include RNAcentral, an international community portal to various databases on noncoding RNA; ValidatorDB, a validation database for protein structures and their ligands; SASBDB, a primary repository for small-angle scattering data of various macromolecular complexes; MoonProt, a database of 'moonlighting' proteins, and two new databases of protein-protein and other macromolecular complexes, ComPPI and the Complex Portal. This issue also includes an unusually high number of cancer-related databases and other databases dedicated to genomic basics of disease and potential drugs and drug targets. The size of NAR online Molecular Biology Database Collection, http://www.oxfordjournals.org/nar/database/a/, remained approximately the same, following the addition of 74 new resources and removal of 77 obsolete web sites. The entire Database Issue is freely available online on the Nucleic Acids Research web site (http://nar.oxfordjournals.org/).

  20. A comprehensive study into the molecular methodology and molecular biology of methanogenic Archaea

    DEFF Research Database (Denmark)

    Lange, M.; Ahring, Birgitte Kiær

    2001-01-01

    Methanogens belong to the kingdom of Euryarchaeota in the domain of Archaea. The Archaea differ from Bacteria in many aspects important to molecular work. Among these are cell wall composition, their sensitivity to antibiotics, their translation and transcription machinery, and their very strict...... procedures. Efficient genetic manipulation systems, including shuttle and integration vector systems, have appeared for mesophilic, but not for thermophilic species within the last few years and will have a major impact on future investigations of methanogenic molecular biology....... complete methanogenic genomes have been sequenced and published and more are underway. Besides, sequences are known from a multitude of individual genes from methanogens. Standard methods for simple DNA and RNA work can normally be employed, but permeabilization of the cell wall may demand special...

  1. Molecular self-assembly for biological investigations and nanoscale lithography

    Science.gov (United States)

    Cheunkar, Sarawut

    Small, diffusible molecules when recognized by their binding partners, such as proteins and antibodies, trigger enzymatic activity, cell communication, and immune response. Progress in analytical methods enabling detection, characterization, and visualization of biological dynamics at the molecular level will advance our exploration of complex biological systems. In this dissertation, analytical platforms were fabricated to capture membrane-associated receptors, which are essential proteins in cell signaling pathways. The neurotransmitter serotonin and its biological precursor were immobilized on gold substrates coated with self-assembled monolayers (SAMs) of oligo(ethylene glycol)alkanethiols and their reactive derivatives. The SAM-coated substrates present the biologically selective affinity of immobilized molecules to target native membrane-associated receptors. These substrates were also tested for biospecificity using antibodies. In addition, small-molecule-functionalized platforms, expressing neurotransmitter pharmacophores, were employed to examine kinetic interactions between G-protein-coupled receptors and their associated neurotransmitters. The binding interactions were monitored using a quartz crystal microbalance equipped with liquid-flow injection. The interaction kinetics of G-protein-coupled serotonin 1A receptor and 5-hydroxytyptophan-functionalized surfaces were studied in a real-time, label-free environment. Key binding parameters, such as equilibrium dissociation constants, binding rate constants, and dissociative half-life, were extracted. These parameters are critical for understanding and comparing biomolecular interactions in modern biomedical research. By integrating self-assembly, surface functionalization, and nanofabrication, small-molecule microarrays were created for high-throughput screening. A hybrid soft-lithography, called microcontact insertion printing, was used to pattern small molecules at the dilute scales necessary for highly

  2. Biological actions and molecular effects of resveratrol, pterostilbene, and 3′-hydroxypterostilbene

    Directory of Open Access Journals (Sweden)

    Hui-Yun Tsai

    2017-01-01

    Full Text Available Stilbenes are a class of polyphenolic compounds, naturally found in a wide variety of dietary sources such as grapes, berries, peanuts, red wine, and some medicinal plants. There are several well-known stilbenes including trans-resveratrol, pterostilbene, and 3′-hydroxypterostilbene. The core chemical structure of stilbene compounds is 1,2-diphenylethylene. Recently, stilbenes have attracted extensive attention and interest due to their wide range of health-beneficial effects such as anti-inflammation, -carcinogenic, -diabetes, and -dyslipidemia activities. Moreover, accumulating in vitro and in vivo studies have reported that stilbene compounds act as inducers of multiple cell-death pathways such as apoptosis, cell cycle arrest, and autophagy for chemopreventive and chemotherapeutic agents in several types of cancer cells. The aim of this review is to highlight recent molecular findings and biological actions of trans-resveratrol, pterostilbene, and 3′-hydroxypterostilbene.

  3. Nuclear Molecular and Theranostic Imaging for Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Arif Sheikh

    2017-02-01

    Full Text Available Traditional nuclear medicine is rapidly being transformed by the evolving concepts in molecular imaging and theranostics. The utility of new approaches in differentiated thyroid cancer (DTC diagnostics and therapy has not been fully appreciated. The clinical information, relevant to disease management and patient care, obtained by scintigraphy is still being underestimated. There has been a trend towards moving away from the use of radioactive iodine (RAI imaging in the management of the disease. This paradigm shift is supported by the 2015 American Thyroid Association Guidelines (1. A more systematic and comprehensive understanding of disease pathophysiology and imaging methodologies is needed for optimal utilization of different imaging modalities in the management of DTC. There have been significant developments in radiotracer and imaging technology, clinically proven to contribute to the understanding of tumor biology and the clinical assessment of patients with DTC. The research and development in the field continues to evolve, with expected emergence of many novel diagnostic and therapeutic techniques. The role for nuclear imaging applications will continue to evolve and be reconfigured in the changing paradigm. This article aims to review the clinical uses and controversies surrounding the use of scintigraphy, and the information it can provide in assisting in the management and treatment of DTC.

  4. MODEL ORGANISMS USED IN MOLECULAR BIOLOGY OR MEDICAL RESEARCH

    Directory of Open Access Journals (Sweden)

    Pandey Govind

    2011-11-01

    Full Text Available A model organism is a non-human species that is studied to understand specific biological phenomena with the expectation that investigations made in the organism model will provide insight into the workings of other organisms. The model organisms are widely used to explore potential causes and treatments for human as well as animal diseases when experiments on animals or humans would be unfeasible or considered less ethical. Studying model organisms may be informative, but care must be taken when generalizing from one organism to another. Often, model organisms are chosen on the basis that they are amenable to experimental manipulation. When researchers look for an organism to use in their studies, they look for several traits. Among these are size, generation time, accessibility, manipulation, genetics, conservation of mechanisms and potential economic benefit. As comparative molecular biology has become more common, some researchers have sought model organisms from a wider assortment of lineages on the tree of life. There are many model organisms, such as viruses (e.g., Phage lambda virus, Tobacco mosaic virus, etc., bacteria (e.g., Bacillus subtilis, Escherichia coli, Pseudomonas fluorescens, Vibrio fischeri, etc., algae (e.g., Chlamydomonas reinhardtii, Emiliania huxleyi, etc., molds (e.g., Aspergillus nidulans, Neurospora crassa, etc., yeasts (e.g., Saccharomyces cerevisiae, Ustilago maydis, etc., higher plants (e.g., Arabidopsis thaliana, Lemna gibba, Lotus japonicus, Nicotiana tabaccum, Oryza sativa, Physcomitrella patens, Zea mays, etc. and animals (e.g., Caenorhabditis elegans, guinea pig, hamster, mouse, rat, cat, chicken, dog, frog, Hydra, Drosophila melanogaster fruit fly, fish, etc..

  5. STRUCTURAL BIOLOGY AND MOLECULAR MEDICINE RESEARCH PROGRAM (LSBMM)

    Energy Technology Data Exchange (ETDEWEB)

    Eisenberg, David S.

    2008-07-15

    The UCLA-DOE Institute of Genomics and Proteomics is an organized research unit of the University of California, sponsored by the Department of Energy through the mechanism of a Cooperative Agreement. Today the Institute consists of 10 Principal Investigators and 7 Associate Members, developing and applying technologies to promote the biological and environmental missions of the Department of Energy, and 5 Core Technology Centers to sustain this work. The focus is on understanding genomes, pathways and molecular machines in organisms of interest to DOE, with special emphasis on developing enabling technologies. Since it was founded in 1947, the UCLA-DOE Institute has adapted its mission to the research needs of DOE and its progenitor agencies as these research needs have changed. The Institute started as the AEC Laboratory of Nuclear Medicine, directed by Stafford Warren, who later became the founding Dean of the UCLA School of Medicine. In this sense, the entire UCLA medical center grew out of the precursor of our Institute. In 1963, the mission of the Institute was expanded into environmental studies by Director Ray Lunt. I became the third director in 1993, and in close consultation with David Galas and John Wooley of DOE, shifted the mission of the Institute towards genomics and proteomics. Since 1993, the Principal Investigators and Core Technology Centers are entirely new, and the Institute has separated from its former division concerned with PET imaging. The UCLA-DOE Institute shares the space of Boyer Hall with the Molecular Biology Institute, and assumes responsibility for the operation of the main core facilities. Fig. 1 gives the organizational chart of the Institute. Some of the benefits to the public of research carried out at the UCLA-DOE Institute include the following: The development of publicly accessible, web-based databases, including the Database of Protein Interactions, and the ProLinks database of genomicly inferred protein function linkages

  6. Gallic acid: molecular rival of cancer.

    Science.gov (United States)

    Verma, Sharad; Singh, Amit; Mishra, Abha

    2013-05-01

    Gallic acid, a predominant polyphenol, has been shown to inhibit carcinogenesis in animal models and in vitro cancerous cell lines. The inhibitory effect of gallic acid on cancer cell growth is mediated via the modulation of genes which encodes for cell cycle, metastasis, angiogenesis and apoptosis. Gallic acid inhibits activation of NF-κB and Akt signaling pathways along with the activity of COX, ribonucleotide reductase and GSH. Moreover, gallic acid activates ATM kinase signaling pathways to prevent the processes of carcinogenesis. The data so far available, both from in vivo and in vitro studies, indicate that this dietary polyphenol could be promising agent in the field of cancer chemoprevention.

  7. Targets for molecular therapy of skin cancer.

    Science.gov (United States)

    Green, Cheryl L; Khavari, Paul A

    2004-02-01

    Cancers of the skin encompass the first and second most common neoplasms in the United States, epidermal basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), respectively, as well as the melanocytic malignancy, malignant melanoma (MM). Recently identified alterations in the function of specific genes in these cancers provide new potential therapeutic targets. These alterations affect conserved regulators of cellular proliferation and viability, including the Sonic Hedgehog, Ras/Raf, ARF/p53, p16(INK4A)/CDK4/Rb and NF-kappaB pathways. New modalities designed to target these specific proteins may represent promising approaches to therapy of human skin cancers.

  8. [Matrix metalloproteases as molecular markers in gastric cancer].

    Science.gov (United States)

    de la Peña, Sol; Sampieri, Clara L; León-Córdoba, Kenneth

    2010-02-06

    Gastric cancer is the second leading cause of cancer-associated mortality in the world. Prognosis in patients with gastric cancer is difficult to establish because it is commonly diagnosed when gastric wall invasion and metastasis have occurred. Currently, some members of the extracellular matrix metalloproteinases have been identified, whose expression in gastric tumor tissue is significantly elevated compared to healthy gastric tissue. Matrix metalloproteinases are 24 zinc-dependent endopeptidases that catalyze the proteolysis of the extracellular matrix. This degradation allows the cancer cells invade the surrounding stroma and trigger metastasis. Upregulation of certain matrix metalloproteinases in gastric cancer has been associated with a poor prognosis and elevated invasive capacity. This review compiles evidence about the genetic expression of matrix metalloproteinases in gastric cancer and their role in tumour invasion and metastasis, emphasizing their potential as molecular markers of prognosis.

  9. Systems Cancer Biology and the Controlling Mechanisms for the J-Shaped Cancer Dose Response: Towards Relaxing the LNT Hypothesis.

    Science.gov (United States)

    Lou, In Chio; Zhao, Yuchao; Wu, Yingjie; Ricci, Paolo F

    2012-01-01

    The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transformation frequency. J-shaped dose response curves have been captured with consideration of cell cycle checkpoint control mechanisms. The simulation results indicate the shape of the dose response curve relates to the behavior of the saddle-node points of the model in the bifurcation diagram. A simplified version of the model in previous work of the authors was used mathematically to analyze behaviors relating to the saddle-node points for the J-shaped dose response curve. It indicates that low-linear energy transfer (LET) is more likely to have a J-shaped dose response curve. This result emphasizes the significance of systems biology approach, which encourages collaboration of multidiscipline of biologists, toxicologists and mathematicians, to illustrate complex cancer-related events, and confirm the biphasic dose-response at low doses.

  10. Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer

    Directory of Open Access Journals (Sweden)

    Park Hyung Seok

    2012-01-01

    Full Text Available Abstract Background Distant recurrence is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of distant recurrence in patients with breast cancer. Methods In an investigation of 313 women with breast cancer who underwent surgery from 1994 and 2000, the expressions of estrogen and progestrone receptor (ER/PR, and human epithelial receptor-2 (HER2 were evaluated. The subtypes were defined as luminal-A, luminal-HER2, HER2-enriched, and triple negative breast cancer (TNBC according to ER, PR, and HER2 status. Results Bone was the most common site of distant recurrence. The incidence of first distant recurrence site was significantly different among the subtypes. Brain metastasis was more frequent in the luminal-HER2 and TNBC subtypes. In subgroup analysis, overall survival in patients with distant recurrence after 24 months after surgery was significantly different among the subtypes. Conclusions Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer may be considered.

  11. From molecular classification to targeted therapeutics: the changing face of systemic therapy in metastatic gastroesophageal cancer.

    Science.gov (United States)

    Murphy, Adrian; Kelly, Ronan J

    2015-01-01

    Histological classification of adenocarcinoma or squamous cell carcinoma for esophageal cancer or using the Lauren classification for intestinal and diffuse type gastric cancer has limited clinical utility in the management of advanced disease. Germline mutations in E-cadherin (CDH1) or mismatch repair genes (Lynch syndrome) were identified many years ago but given their rarity, the identification of these molecular alterations does not substantially impact treatment in the advanced setting. Recent molecular profiling studies of upper GI tumors have added to our knowledge of the underlying biology but have not led to an alternative classification system which can guide clinician's therapeutic decisions. Recently the Cancer Genome Atlas Research Network has proposed four subtypes of gastric cancer dividing tumors into those positive for Epstein-Barr virus, microsatellite unstable tumors, genomically stable tumors, and tumors with chromosomal instability. Unfortunately to date, many phase III clinical trials involving molecularly targeted agents have failed to meet their survival endpoints due to their use in unselected populations. Future clinical trials should utilize molecular profiling of individual tumors in order to determine the optimal use of targeted therapies in preselected patients.

  12. From Molecular Classification to Targeted Therapeutics: The Changing Face of Systemic Therapy in Metastatic Gastroesophageal Cancer

    Directory of Open Access Journals (Sweden)

    Adrian Murphy

    2015-01-01

    Full Text Available Histological classification of adenocarcinoma or squamous cell carcinoma for esophageal cancer or using the Lauren classification for intestinal and diffuse type gastric cancer has limited clinical utility in the management of advanced disease. Germline mutations in E-cadherin (CDH1 or mismatch repair genes (Lynch syndrome were identified many years ago but given their rarity, the identification of these molecular alterations does not substantially impact treatment in the advanced setting. Recent molecular profiling studies of upper GI tumors have added to our knowledge of the underlying biology but have not led to an alternative classification system which can guide clinician’s therapeutic decisions. Recently the Cancer Genome Atlas Research Network has proposed four subtypes of gastric cancer dividing tumors into those positive for Epstein-Barr virus, microsatellite unstable tumors, genomically stable tumors, and tumors with chromosomal instability. Unfortunately to date, many phase III clinical trials involving molecularly targeted agents have failed to meet their survival endpoints due to their use in unselected populations. Future clinical trials should utilize molecular profiling of individual tumors in order to determine the optimal use of targeted therapies in preselected patients.

  13. Microgravity research in plant biological systems: Realizing the potential of molecular biology

    Science.gov (United States)

    Lewis, Norman G.; Ryan, Clarence A.

    1993-01-01

    The sole all-pervasive feature of the environment that has helped shape, through evolution, all life on Earth is gravity. The near weightlessness of the Space Station Freedom space environment allows gravitational effects to be essentially uncoupled, thus providing an unprecedented opportunity to manipulate, systematically dissect, study, and exploit the role of gravity in the growth and development of all life forms. New and exciting opportunities are now available to utilize molecular biological and biochemical approaches to study the effects of microgravity on living organisms. By careful experimentation, we can determine how gravity perception occurs, how the resulting signals are produced and transduced, and how or if tissue-specific differences in gene expression occur. Microgravity research can provide unique new approaches to further our basic understanding of development and metabolic processes of cells and organisms, and to further the application of this new knowledge for the betterment of humankind.

  14. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes

    Science.gov (United States)

    de Anda-Jáuregui, Guillermo; Velázquez-Caldelas, Tadeo E.; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2016-01-01

    Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples) is also inferred and analyzed. Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e., CNR2) or to a particular subtype (such as LCK). Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance. With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer. PMID:27920729

  15. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes

    Directory of Open Access Journals (Sweden)

    Guillermo de Anda-Jáuregui

    2016-11-01

    Full Text Available Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes.In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples is also inferred and analyzed.Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e. CNR2 or to a particular subtype (such as LCK. Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance.With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer.

  16. Transcriptional Network Architecture of Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    de Anda-Jáuregui, Guillermo; Velázquez-Caldelas, Tadeo E; Espinal-Enríquez, Jesús; Hernández-Lemus, Enrique

    2016-01-01

    Breast cancer heterogeneity is evident at the clinical, histological and molecular level. High throughput technologies allowed the identification of intrinsic subtypes that capture transcriptional differences among tumors. A remaining question is whether said differences are associated to a particular transcriptional program which involves different connections between the same molecules. In other words, whether particular transcriptional network architectures can be linked to specific phenotypes. In this work we infer, construct and analyze transcriptional networks from whole-genome gene expression microarrays, by using an information theory approach. We use 493 samples of primary breast cancer tissue classified in four molecular subtypes: Luminal A, Luminal B, Basal and HER2-enriched. For comparison, a network for non-tumoral mammary tissue (61 samples) is also inferred and analyzed. Transcriptional networks present particular architectures in each breast cancer subtype as well as in the non-tumor breast tissue. We find substantial differences between the non-tumor network and those networks inferred from cancer samples, in both structure and gene composition. More importantly, we find specific network architectural features associated to each breast cancer subtype. Based on breast cancer networks' centrality, we identify genes previously associated to the disease, either, generally (i.e., CNR2) or to a particular subtype (such as LCK). Similarly, we identify LUZP4, a gene barely explored in breast cancer, playing a role in transcriptional networks with subtype-specific relevance. With this approach we observe architectural differences between cancer and non-cancer at network level, as well as differences between cancer subtype networks which might be associated with breast cancer heterogeneity. The centrality measures of these networks allow us to identify genes with potential biomedical implications to breast cancer.

  17. The roles of integration in molecular systems biology.

    Science.gov (United States)

    O'Malley, Maureen A; Soyer, Orkun S

    2012-03-01

    A common way to think about scientific practice involves classifying it as hypothesis- or data-driven. We argue that although such distinctions might illuminate scientific practice very generally, they are not sufficient to understand the day-to-day dynamics of scientific activity and the development of programmes of research. One aspect of everyday scientific practice that is beginning to gain more attention is integration. This paper outlines what is meant by this term and how it has been discussed from scientific and philosophical points of view. We focus on methodological, data and explanatory integration, and show how they are connected. Then, using some examples from molecular systems biology, we will show how integration works in a range of inquiries to generate surprising insights and even new fields of research. From these examples we try to gain a broader perspective on integration in relation to the contexts of inquiry in which it is implemented. In today's environment of data-intensive large-scale science, integration has become both a practical and normative requirement with corresponding implications for meta-methodological accounts of scientific practice. We conclude with a discussion of why an understanding of integration and its dynamics is useful for philosophy of science and scientific practice in general.

  18. Diagnosis of Mycobacterium tuberculosis using molecular biology technology

    Institute of Scientific and Technical Information of China (English)

    Juan Garberi; Jorge Labrador; Federico Garberi; Juan Ezequiel Garberi; Julian Peneipil; Miguel Garberi; Luis Scigliano; Alcides Troncoso

    2011-01-01

    Objective:To present an integrated molecular biology dedicated system for tuberculosis diagnosis.Methods:One hundred and five sputum specimens from patients strongly suspected by clinical parameters of tuberculosis were studied by Ziehl-Neelsen staining, by cultivation on solid medium and by a balanced heminested fluorometricPCR system (OrangeG3TB) that could preserve worker safety and produce a rather pure material free of potential inhibitors. DNA amplification was performed in a low cost tuberculosis termocycler-fluorometer. Produced double stranded DNA was flurometrically detected. The whole reaction was conducted in one single tube which would not be opened after adding the processed sample in order to minimize the risk of cross contamination with amplicons.Results: The assay was able to detect30 bacillus per sample mL with99.8% interassay variation coefficient.PCR was positive in23 (21.9%) tested samples (21 of them were smear negative). In our study it showed a preliminary sensitivity of 94.5% for sputum and an overall specificity of98.7%.Conclusions:Total run time of the test is4 h with2.5 real working time. AllPCR positive samples are also positive by microbiological culture and clinical criteria. Results show that it could be a very useful tool to increase detection efficiency of tuberculosis disease in low bacilus load samples. Furthermore, its low cost and friendly using make it feasible to run in poor regions.

  19. Do biological molecular machines act as Maxwell's demons?

    CERN Document Server

    Kurzynski, Michal

    2014-01-01

    In the intention of its creator, Maxwell's demon was thought to be an intelligent being able to perform work at the expense of the entropy reduction of a closed operating system. The perplexing notion of the demon's intelligence was formalized in terms of the memory and information processing by Szilard and followers. A non-informational formulation of the problem was proposed by Smoluchowski and popularized by Feynman as the ratchet and pawl machine. A. F. Huxley and followers adopted this way of thinking to propose numerous ratchet mechanisms of the protein molecular machines action, but no entropy reduction takes place for these models. More general models of protein dynamics have been proposed with a number of intramolecular states organized in a network of stochastic transitions. Here, a computer realization of such a network is investigated, displaying, like networks of the systems biology, a transition from the fractal organization on a small length-scale to the small-world organization on the large le...

  20. RT-PCR Protocols - Methods in Molecular Biology

    Directory of Open Access Journals (Sweden)

    Manuela Monti

    2011-03-01

    Full Text Available “The first record I have of it, is when I made a computer file which I usually did whenever I had an idea, that would have been on the Monday when I got back, and I called it Chain Reaction.POL, meaning polymerase. That was the identifier for it and later I called the thing the Polymerase Chain Reaction, which a lot of people thought was a dumb name for it, but it stuck, and it became PCR”. With these words the Nobel prize winner, Kary Mullis, explains how he named the PCR: one of the most important techniques ever invented and currently used in molecular biology. This book “RT-PCR Protocols” covers a wide range of aspects important for the setting of a PCR experiment for both beginners and advanced users. In my opinion the book is very well structured in three different sections. The first one describes the different technologies now available, like competitive RT-PCR, nested RT-PCR or RT-PCR for cloning. An important part regards the usage of PCR in single cell mouse embryos, stressing how important...........

  1. Molecular depth profiling of organic and biological materials

    Energy Technology Data Exchange (ETDEWEB)

    Fletcher, John S. [Surface Analysis Research Centre, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom)]. E-mail: John.Fletcher@manchester.ac.uk; Conlan, Xavier A. [Surface Analysis Research Centre, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom); Lockyer, Nicholas P. [Surface Analysis Research Centre, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom); Vickerman, John C. [Surface Analysis Research Centre, School of Chemical Engineering and Analytical Science, University of Manchester, Manchester M60 1QD (United Kingdom)

    2006-07-30

    Atomic depth profiling using secondary ion mass spectrometry, SIMS, is common in the field micro-electronics; however, the generation of molecular information as a function of sample depth is difficult due to the accumulation of damage both on and beneath the sample surface. The introduction of polyatomic ion beams such as SF{sub 5} and C{sub 60} have raised the possibility of overcoming this problem as they deposit the majority of their energy in the upper surface of the sample resulting in increased sputter yields but with a complimentary reduction in sub-surface damage accumulation. In this paper we report the depth profile analysis of the bio-polymer polycaprolactone, PCL, using the polyatomic ions Au{sub 3}{sup +} and C{sub 60}{sup +} and the monoatomic Au{sup +}. Results are compared to recent analysis of a similar sample using SF{sub 5}{sup +}. C{sub 60}{sup +} depth profiling of cellulose is also demonstrated, an experiment that has been reported as unsuccessful when attempted with SF{sub 5}{sup +} implications for biological analysis are discussed.

  2. How molecular should your molecular model be? On the level of molecular detail required to simulate biological networks in systems and synthetic biology.

    Science.gov (United States)

    Gonze, Didier; Abou-Jaoudé, Wassim; Ouattara, Djomangan Adama; Halloy, José

    2011-01-01

    The recent advance of genetic studies and the rapid accumulation of molecular data, together with the increasing performance of computers, led researchers to design more and more detailed mathematical models of biological systems. Many modeling approaches rely on ordinary differential equations (ODE) which are based on standard enzyme kinetics. Michaelis-Menten and Hill functions are indeed commonly used in dynamical models in systems and synthetic biology because they provide the necessary nonlinearity to make the dynamics nontrivial (i.e., limit-cycle oscillations or multistability). For most of the systems modeled, the actual molecular mechanism is unknown, and the enzyme equations should be regarded as phenomenological. In this chapter, we discuss the validity and accuracy of these approximations. In particular, we focus on the validity of the Michaelis-Menten function for open systems and on the use of Hill kinetics to describe transcription rates of regulated genes. Our discussion is illustrated by numerical simulations of prototype systems, including the Repressilator (a genetic oscillator) and the Toggle Switch model (a bistable system). We systematically compare the results obtained with the compact version (based on Michaelis-Menten and Hill functions) with its corresponding developed versions (based on "elementary" reaction steps and mass action laws). We also discuss the use of compact approaches to perform stochastic simulations (Gillespie algorithm). On the basis of these results, we argue that using compact models is suitable to model qualitatively biological systems.

  3. Molecular genetics and genomics progress in urothelial bladder cancer.

    Science.gov (United States)

    Netto, George J

    2013-11-01

    The clinical management of solid tumor patients has recently undergone a paradigm shift as the result of the accelerated advances in cancer genetics and genomics. Molecular diagnostics is now an integral part of routine clinical management in lung, colon, and breast cancer patients. In a disappointing contrast, molecular biomarkers remain largely excluded from current management algorithms of urologic malignancies. The need for new treatment alternatives and validated prognostic molecular biomarkers that can help clinicians identify patients in need of early aggressive management is pressing. Identifying robust predictive biomarkers that can stratify response to newly introduced targeted therapeutics is another crucially needed development. The following is a brief discussion of some promising candidate biomarkers that may soon become a part of clinical management of bladder cancers.

  4. Molecular therapy of colorectal cancer: progress and future directions.

    Science.gov (United States)

    Weng, Wenhao; Feng, Junlan; Qin, Huanlong; Ma, Yanlei

    2015-02-01

    Colorectal cancer (CRC) remains one of the most common types of cancer and leading causes of cancer death worldwide. Although the introduction of cytotoxic drugs such as oxaliplatin, irinotecan and fluorouracil has improved the treatment of advanced CRC, the individual response to chemoradiotherapy varies tremendously from one patient to another. However, recent progress in CRC molecular therapies may provide new insight into the treatment of this disease. Currently, components of the EGFR, VEGF, Wnt and NF-kB pathways are the most important targets for CRC therapy. This review chronicles the development of molecular CRC therapies over the past few decades. We also provide an update on the current progress of research concerning the molecular pathways leading to CRC and discuss the possible implications for CRC therapy.

  5. Abstracts of the 26. Annual meeting of the Brazilian Society on Biochemistry and Molecular Biology; Resumos da 26. reuniao anual da Sociedade Brasileira de Bioquimica e Biologia Molecular

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-07-01

    This meeting was about biochemistry and molecular biology. It was discussed topics related to bio energetic, channels, transports, biotechnology, metabolism, cellular biology, immunology, toxicology, photobiology and pharmacology.

  6. Abstracts of the 27. Annual meeting of the Brazilian Society on Biochemistry and Molecular Biology; Resumos da 27. reuniao anual da Sociedade Brasileira de Bioquimica e Biologia Molecular

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-07-01

    This meeting was about biochemistry and molecular biology. It was discussed topics related to bio energetic, channels, transports, biotechnology, metabolism, cellular biology, immunology, toxicology, photobiology and pharmacology.

  7. Molecular targeted agents for gastric and gastroesophageal junction cancer.

    Science.gov (United States)

    Oshima, Takashi; Masuda, Munetaka

    2012-04-01

    Despite recent improvements in surgical techniques and chemotherapy, advanced cancers of the stomach and gastroesophageal junction (GEJ) continue to have poor clinical outcomes. However, molecules intimately related to cancer cell proliferation, invasion, and metastasis have been studied as candidates for molecular targeted agents. Target molecules, such as the epidermal growth factor receptor, vascular endothelial growth factor receptor, and P13k/Akt/mTor pathway, as well as the insulin-like growth factor receptor, c-Met pathways, fibroblast growth factor receptor, and other pathways are considered to be promising candidates for molecular targeted therapy for gastric and GEJ cancer. In this review we focus on the recent developments in targeting relevant pathways in these types of cancer.

  8. Proteoglycans in cancer biology, tumour microenvironment and angiogenesis.

    Science.gov (United States)

    Iozzo, Renato V; Sanderson, Ralph D

    2011-05-01

    Proteoglycans, key molecular effectors of cell surface and pericellular microenvironments, perform multiple functions in cancer and angiogenesis by virtue of their polyhedric nature and their ability to interact with both ligands and receptors that regulate neoplastic growth and neovascularization. Some proteoglycans such as perlecan, have pro- and anti-angiogenic activities, whereas other proteoglycans, such as syndecans and glypicans, can also directly affect cancer growth by modulating key signalling pathways. The bioactivity of these proteoglycans is further modulated by several classes of enzymes within the tumour microenvironment: (i) sheddases that cleave transmembrane or cell-associated syndecans and glypicans, (ii) various proteinases that cleave the protein core of pericellular proteoglycans and (iii) heparanases and endosulfatases which modify the structure and bioactivity of various heparan sulphate proteoglycans and their bound growth factors. In contrast, some of the small leucine-rich proteoglycans, such as decorin and lumican, act as tumour repressors by physically antagonizing receptor tyrosine kinases including the epidermal growth factor and the Met receptors or integrin receptors thereby evoking anti-survival and pro-apoptotic pathways. In this review we will critically assess the expanding repertoire of molecular interactions attributed to various proteoglycans and will discuss novel proteoglycan functions modulating cancer progression, invasion and metastasis and how these factors regulate the tumour microenvironment.

  9. Molecular Pathology of Pancreatic Cancer: From Bench-to-Bedside Translation

    Science.gov (United States)

    Corbo, Vincenzo; Tortora, Giampaolo; Scarpa, Aldo

    2012-01-01

    Pancreatic ductal adenocarcinoma (referred here as pancreatic cancer) is a lethal disease with the worst prognosis among all solid tumors. Surgical resection represents the only hope for cure but it is possible only in patients that present with local disease (about 20% of cases). Whether dismal prognosis of pancreatic cancer is a result of late diagnosis or early dissemination to distant organ is still a debate. Moreover, this disease shows an intrinsic chemotherapeutic resistance that has been mainly ascribed to the presence of a dense stromal reaction that significantly impairs drugs delivery. Clinical management of pancreatic cancer patients relies on few molecular markers (e.g., the diagnostic marker CA19-9) that, however, present several limitations to their use. The clinical usefulness of somatic alterations in well-characterized genes (such as KRAS and TP53), whose detection is technically feasible in different biological samples, has been extensively investigated leading to inconsistent results. Furthermore, none of the candidate molecular markers identified in recent years has shown an appropriate clinical performance and therefore none is routinely used. This depicts a scenario where the identification of novel and effective clinical biomarkers is mandatory. Very recent genome-wide comprehensive studies have shed light on the high degree of genetic complexity and heterogeneity of the pancreatic cancers. Although far from being introduced into the clinical settings, results from those studies are expected to change definitively the perspective through which we look at the clinical management of pancreatic cancer patients towards a personalized cancer medicine. PMID:22458520

  10. Molecular mechanisms of TRAIL-induced apoptosis of cancer cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) is a recently identified member of the tumor necrosis factor (TNF) family[1]. Numerous studies indicate that TRAIL can induce apoptosis of cancer cells but not of normal cells, pointing to the possibility of de-veloping TRAIL into a cancer drug[2-4]. This review will summary the molecular mechanisms of TRAIL-induced apoptosis and discuss the questions to be resolved in this field.

  11. Just Working with the Cellular Machine: A High School Game for Teaching Molecular Biology

    Science.gov (United States)

    Cardoso, Fernanda Serpa; Dumpel, Renata; Gomes da Silva, Luisa B.; Rodrigues, Carlos R.; Santos, Dilvani O.; Cabral, Lucio Mendes; Castro, Helena C.

    2008-01-01

    Molecular biology is a difficult comprehension subject due to its high complexity, thus requiring new teaching approaches. Herein, we developed an interdisciplinary board game involving the human immune system response against a bacterial infection for teaching molecular biology at high school. Initially, we created a database with several…

  12. Digital learning material for experimental design and model building in molecular biology

    NARCIS (Netherlands)

    Aegerter-Wilmsen, T.

    2005-01-01

    Designing experimental approaches is a major cognitive skill in molecular biology research, and building models, including quantitative ones, is a cognitive skill which is rapidly gaining importance. Since molecular biology education at university level is aimed at educating future researchers, we c

  13. 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

    reveal the molecular differences between cancer and normal that may be exploited to therapeutic benefit or that provide targets for molecular assays that may enable early cancer detection, and predict individual disease progression or response to treatment. This chapter reviews current and future directions in genome analysis and summarizes studies that provide insights into breast cancer pathophysiology or that suggest strategies to improve breast cancer management.

  14. DNA aptamers as molecular probes for colorectal cancer study.

    Directory of Open Access Journals (Sweden)

    Kwame Sefah

    Full Text Available BACKGROUND: Understanding the molecular features of specific tumors can increase our knowledge about the mechanism(s underlying disease development and progression. This is particularly significant for colorectal cancer, which is a heterogeneous complex of diseases developed in a sequential manner through a multistep carcinogenic process. As such, it is likely that tumors with similar characteristics might originate in the same manner and have a similar molecular behavior. Therefore, specific mapping of the molecular features can be potentially useful for both tumor classification and the development of appropriate therapeutic regimens. However, this can only be accomplished by developing high-affinity molecular probes with the ability to recognize specific markers associated with different tumors. Aptamers can most easily meet this challenge based on their target diversity, flexible manipulation and ease of development. METHODOLOGY AND RESULTS: Using a method known as cell-based Systematic Evolution of Ligands by Exponential enrichment (cell-SELEX and colorectal cancer cultured cell lines DLD-1 and HCT 116, we selected a panel of target-specific aptamers. Binding studies by flow cytometry and confocal microscopy showed that these aptamers have high affinity and selectivity. Our data further show that these aptamers neither recognize normal colon cells (cultured and fresh, nor do they recognize most other cancer cell lines tested. CONCLUSION/SIGNIFICANCE: The selected aptamers can identify specific biomarkers associated with colorectal cancers. We believe that these probes could be further developed for early disease detection, as well as prognostic markers, of colorectal cancers.

  15. The 2011 Nucleic Acids Research Database Issue and the online Molecular Biology Database Collection.

    Science.gov (United States)

    Galperin, Michael Y; Cochrane, Guy R

    2011-01-01

    The current 18th Database Issue of Nucleic Acids Research features descriptions of 96 new and 83 updated online databases covering various areas of molecular biology. It includes two editorials, one that discusses COMBREX, a new exciting project aimed at figuring out the functions of the 'conserved hypothetical' proteins, and one concerning BioDBcore, a proposed description of the 'minimal information about a biological database'. Papers from the members of the International Nucleotide Sequence Database collaboration (INSDC) describe each of the participating databases, DDBJ, ENA and GenBank, principles of data exchange within the collaboration, and the recently established Sequence Read Archive. A testament to the longevity of databases, this issue includes updates on the RNA modification database, Definition of Secondary Structure of Proteins (DSSP) and Homology-derived Secondary Structure of Proteins (HSSP) databases, which have not been featured here in >12 years. There is also a block of papers describing recent progress in protein structure databases, such as Protein DataBank (PDB), PDB in Europe (PDBe), CATH, SUPERFAMILY and others, as well as databases on protein structure modeling, protein-protein interactions and the organization of inter-protein contact sites. Other highlights include updates of the popular gene expression databases, GEO and ArrayExpress, several cancer gene databases and a detailed description of the UK PubMed Central project. The Nucleic Acids Research online Database Collection, available at: http://www.oxfordjournals.org/nar/database/a/, now lists 1330 carefully selected molecular biology databases. The full content of the Database Issue is freely available online at the Nucleic Acids Research web site (http://nar.oxfordjournals.org/).

  16. Transcriptional networks inferred from molecular signatures of breast cancer.

    Science.gov (United States)

    Tongbai, Ron; Idelman, Gila; Nordgard, Silje H; Cui, Wenwu; Jacobs, Jonathan L; Haggerty, Cynthia M; Chanock, Stephen J; Børresen-Dale, Anne-Lise; Livingston, Gary; Shaunessy, Patrick; Chiang, Chih-Hung; Kristensen, Vessela N; Bilke, Sven; Gardner, Kevin

    2008-02-01

    Global genomic approaches in cancer research have provided new and innovative strategies for the identification of signatures that differentiate various types of human cancers. Computational analysis of the promoter composition of the genes within these signatures may provide a powerful method for deducing the regulatory transcriptional networks that mediate their collective function. In this study we have systematically analyzed the promoter composition of gene classes derived from previously established genetic signatures that recently have been shown to reliably and reproducibly distinguish five molecular subtypes of breast cancer associated with distinct clinical outcomes. Inferences made from the trends of transcription factor binding site enrichment in the promoters of these gene groups led to the identification of regulatory pathways that implicate discrete transcriptional networks associated with specific molecular subtypes of breast cancer. One of these inferred pathways predicted a role for nuclear factor-kappaB in a novel feed-forward, self-amplifying, autoregulatory module regulated by the ERBB family of growth factor receptors. The existence of this pathway was verified in vivo by chromatin immunoprecipitation and shown to be deregulated in breast cancer cells overexpressing ERBB2. This analysis indicates that approaches of this type can provide unique insights into the differential regulatory molecular programs associated with breast cancer and will aid in identifying specific transcriptional networks and pathways as potential targets for tumor subtype-specific therapeutic intervention.

  17. Colorectal Cancer & Molecular Mutations and Polymorphism

    Directory of Open Access Journals (Sweden)

    Aga Syed Sameer

    2013-05-01

    Full Text Available Colorectal cancer (CRC is one of the major causes of mortality and morbidity, and is the third most common cancer in men and the second most common cancer in women worldwide. The incidence of CRC shows considerable variation among racially or ethnically defined populations in multiracial/ethnic countries. The tumorigenesis of CRC is either because of the chromosomal instability (CIN or microsatellite instability (MIN or involving various proto-oncogenes, tumor suppressor genes and also epigenetic changes in the DNA. In this review I have focused on the mutations and polymorphisms of various important genes of the CIN and MIN pathways which have been implicated in the development of CRC.

  18. Correlation of morphological and molecular parameters for colon cancer

    Science.gov (United States)

    Yuan, Shuai; Roney, Celeste A.; Li, Qian; Jiang, James; Cable, Alex; Summers, Ronald M.; Chen, Yu

    2010-02-01

    Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. There is great interest in studying the relationship among microstructures and molecular processes of colorectal cancer during its progression at early stages. In this study, we use our multi-modality optical system that could obtain co-registered optical coherence tomography (OCT) and fluorescence molecular imaging (FMI) images simultaneously to study CRC. The overexpressed carbohydrate α-L-fucose on the surfaces of polyps facilitates the bond of adenomatous polyps with UEA-1 and is used as biomarker. Tissue scattering coefficient derived from OCT axial scan is used as quantitative value of structural information. Both structural images from OCT and molecular images show spatial heterogeneity of tumors. Correlations between those values are analyzed and demonstrate that scattering coefficients are positively correlated with FMI signals in conjugated. In UEA-1 conjugated samples (8 polyps and 8 control regions), the correlation coefficient is ranged from 0.45 to 0.99. These findings indicate that the microstructure of polyps is changed gradually during cancer progression and the change is well correlated with certain molecular process. Our study demonstrated that multi-parametric imaging is able to simultaneously detect morphology and molecular information and it can enable spatially and temporally correlated studies of structure-function relationships during tumor progression.

  19. Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran-pyrazole derivatives as anticancer agents.

    Science.gov (United States)

    Abd El-Karim, Somaia S; Anwar, Manal M; Mohamed, Neama A; Nasr, Tamer; Elseginy, Samia A

    2015-12-01

    This study deals with design and synthesis of novel benzofuran-pyrazole hybrids as anticancer agents. Eight compounds were chosen by National Cancer Institute (NCI), USA to evaluate their in vitro antiproliferative activity at 10(-5)M in full NCI 60 cell panel. The preliminary screening of the tested compounds showed promising broad-spectrum anticancer activity. Compound 4c was further assayed for five dose molar ranges in full NCI 60 cell panel and exhibited remarkable growth inhibitory activity pattern against Leukemia CCRF-CEM, MOLT-4, Lung Cancer HOP-92, Colon Cancer HCC-2998, CNS Cancer SNB-75, Melanoma SK-MEL-2, Ovarian Cancer IGROV1, Renal Cancer 786-0, RXF 393, Breast Cancer HS 578T and T-47D (GI50: 1.00-2.71μM). Moreover, enzyme assays were carried out to investigate the possible antiproliferative mechanism of action of compound 4c. The results revealed that compound 4c has good c-Src inhibitory activity at 10μM. In addition, molecular docking studies showed that 4c could bind to the ATP Src pocket sites. Fulfilling the Lipinskiís rule of five in addition to its ADME profile and the biological results, all strongly suggest that 4c is a promising Src kinase inhibitor.

  20. Molecular biology in radiation oncology. Radiation oncology perspective of BRCA1 and BRCA2

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, C.N. [Harvard Medical School (United States). Joint Center for Radiation Therapy

    1999-07-01

    The breast cancer susceptibility genes, BRCA1 and BRCA2, are used to illustrate the application of molecular biology to clinical radiation oncology. Identified by linkage analysis and cloned, the structure of the genes and the numerous mutations are determined by molecular biology techniques that examine the structure of the DNA and the proteins made by the normal and mutant alleles. Mutations in the non-transcribed portion of the gene will not be found in protein structure assays and may be important in gene function. In addition to potential deleterious mutations, normal polymorphisms of the gene will also be detected, therefore not all differences in gene sequence may represent important mutations, a finding that complicates genetic screening and counseling. The localization of the protein in the nucleus, the expression in relation to cell cycle and the association with RAD51 led to the discovery that the two BRCA genes may be involved in transcriptional regulation and DNA repair. The defect in DNA repair can increase radiosensitivity which might improve local control using breast-conserving treatment in a tumor which is homozygous for the loss of the gene (i.e., BRCA1 and BRCA2 are tumor suppressor genes). This is supported by the early reports of a high rate of local control with breast-conserving therapy. Nonetheless, this radiosensitivity theoretically may also lead to increased susceptibility to carcinogenic effects in surviving cells, a finding that might not be observed for decades. The susceptibility to radiation-induced DNA damage appears also to make the cells more sensitive to chemotherapy. Understanding the role of the normal BRCA genes in DNA repair might help define a novel mechanism for radiation sensitization by interfering with the normal gene function using a variety of molecular or biochemical therapies.

  1. Aptamers generated from cell-SELEX for molecular medicine: a chemical biology approach.

    Science.gov (United States)

    Fang, Xiaohong; Tan, Weihong

    2010-01-19

    Molecular medicine is an emerging field focused on understanding the molecular basis of diseases and translating this information into strategies for diagnosis and therapy. This approach could lead to personalized medical treatments. Currently, our ability to understand human diseases at the molecular level is limited by the lack of molecular tools to identify and characterize the distinct molecular features of the disease state, especially for diseases such as cancer. Among the new tools being developed by researchers including chemists, engineers, and other scientists is a new class of nucleic acid probes called aptamers, which are ssDNA/RNA molecules selected to target a wide range of molecules and even cells. In this Account, we will focus on the use of aptamers, generated from cell-based selections, as a novel molecular tool for cancer research. Cancers originate from mutations of human genes. These genetic alterations result in molecular changes to diseased cells, which, in turn, lead to changes in cell morphology and physiology. For decades, clinicians have diagnosed cancers primarily based on the morphology of tumor cells or tissues. However, this method does not always give an accurate diagnosis and does not allow clinicians to effectively assess the complex molecular alterations that are predictive of cancer progression. As genomics and proteomics do not yet allow a full access to this molecular knowledge, aptamer probes represent one effective and practical avenue toward this goal. One special feature of aptamers is that we can isolate them by selection against cancer cells without prior knowledge of the number and arrangement of proteins on the cellular surface. These probes can identify molecular differences between normal and tumor cells and can discriminate among tumor cells of different classifications, at different disease stages, or from different patients. This Account summarizes our recent efforts to develop aptamers through cell-SELEX for the

  2. 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

  3. Advanced imaging of colorectal cancer: From anatomy to molecular imaging

    OpenAIRE

    García-Figueiras, Roberto; Baleato-González, Sandra; Padhani, Anwar R.; Marhuenda, Ana; Luna, Antonio; Alcalá, Lidia; Carballo-Castro, Ana; Álvarez-Castro, Ana

    2016-01-01

    Abstract Imaging techniques play a key role in the management of patients with colorectal cancer. The introduction of new advanced anatomical, functional, and molecular imaging techniques may improve the assessment of diagnosis, prognosis, planning therapy, and assessment of response to treatment of these patients. Functional and molecular imaging techniques in clinical practice may allow the assessment of tumour-specific characteristics and tumour heterogeneity. This paper will review recent...

  4. Clinical variability and molecular heterogeneity in prostate cancer

    Directory of Open Access Journals (Sweden)

    Jonathan Shoag

    2016-01-01

    Full Text Available Prostate cancer is a clinically heterogeneous disease, with some men having indolent disease that can safely be observed, while others have aggressive, lethal disease. Over the past decade, researchers have begun to unravel some of the genomic heterogeneity that contributes to these varying clinical phenotypes. Distinct molecular sub-classes of prostate cancer have been identified, and the uniqueness of these sub-classes has been leveraged to predict clinical outcomes, design novel biomarkers for prostate cancer diagnosis, and develop novel therapeutics. Recent work has also elucidated the temporal and spatial heterogeneity of prostate cancer, helping us understand disease pathogenesis, response to therapy, and progression. New genomic techniques have provided us with a window into the remarkable clinical and genomic heterogeneity of prostate cancer, and this new perspective will increasingly impact patient care.

  5. The molecular biology and diagnostics of Chlamydia trachomatis.

    Science.gov (United States)

    Birkelund, S

    1992-08-01

    The rapid development of biotechnological methods provides the potential of dissecting the molecular structure of microorganisms. In this review the molecular biology of chlamydia is described. The genus Chlamydia contains three species C. trachomatis, C. psittaci, and C. pneumonia which all are important human pathogens. Chlamydia is obligate intracellular bacteria with a unique biphasic life cycle. The extracellularly chlamydial elementary bodies (EB) are small, metabolic inactive, infectious particles with a tight outer cell membrane. After internalization into host cells the chlamydial structure changes, they transform to reticulated bodies (RB) which become larger, metabolically active, and start to replicate. Fourtysix hrs post infection RB reorganizes to EB followed by burst of the inclusion. The structure of the EB outer membrane differs from the membrane of gram-negative bacteria since it is highly cross-linked by S-S bridges. There are, however, also similarities to gram-negative cell walls. The chlamydial major outer membrane protein, Omp1, forms pores and is closely associated with lipopolysaccharide, LPS. LPS, however, is more loosely associated with Omp1 than in other gram negative bacteria since incubation of EB with antibodies against LPS will liberate it from the chlamydial surface. Therefore the surface localized LPS may be important for chlamydial survival. OMP1 varies between the different serovar of C. trachomatis. Several very conserved regions are separated by variable domains. The variable domains are very antigenic and are localized at the surface of EB. After chlamydial internalization into the host cell transition to RB starts. Some of the early proteins are DnaK-like and groEL-like heat-shock proteins. The chlamydial DnaK-like protein is very antigenic. Patient serum samples will recognize the chlamydial DnaK-like protein. From the determined DNA sequence the amino acid sequence was determined. It was 57% homologous to the Eschrichia

  6. [Advances of molecular targeted therapy in squamous cell lung cancer].

    Science.gov (United States)

    Ma, Li; Zhang, Shucai

    2013-12-01

    Squamous cell lung cancer (SQCLC) is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR) inhibitors or anaplastic lymphoma kinase (ALK) inhibitors that show exquisite activity in lung adenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4)-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1) gene, the discoidin domain receptor 2 (DDR2) gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lung cancer assessing the value of novel therapeutics addressing these targets.

  7. Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

    Directory of Open Access Journals (Sweden)

    Bruna Karina Banin Hirata

    2014-01-01

    Full Text Available Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity.

  8. Molecular-Genetic Aspects of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Krasteva M.

    2014-12-01

    Full Text Available Breast cancer is the most frequent malignancy among women. Advances in breast cancer knowledge have deciphered the involvement of a number of tumor suppressor genes and proto-oncogenes in disease pathogenesis. These genes are part of the complex biochemical pathways, which enable cell cycle control and maintenance of genome integrity. Their function may be disrupted as a result of alterations in gene sequence or misregulation of gene expression including alterations in DNA methylation pattern. The present review summarizes the main findings on major breast cancer related genes BRCA1/2, p53, ATM, CHEK2, HER2, PIK3CA and their tumorigenic inactivation/activation. The potential clinical importance of these genes with respect to patients’ prognosis and therapy are also discussed. The possible implication of other putative breast cancer related genes is also outlined. The first elaborate data on the genetic and epigenetic status of the above mentioned genes concerning Bulgarian patients with the sporadic form of the disease are presented. The studies indicate for a characteristic mutational spectrum in some of the genes for the Bulgarian patients and specific correlation between the status of different genes and clinicopathological characteristics.

  9. Molecular biological enhancement of coal biodesulfurization. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Litchfield, J.H.; Zupancic, T.J.; Kittle, J.D. Jr.; Baker, B.; Palmer, D.T.; Traunero, C.G.; Wyza, R.E.; Schweitzer, A.; Conkle, H.N. [Battelle, Columbus, OH (United States); Chakravarty, L.; Tuovinen, O.H. [Ohio State Univ., Columbus, OH (United States)

    1992-10-08

    Progress is reported in understanding Thiobacillus molecular biology, specifically in the area of vector development. At the initiation of this program, the basic elements needed for performing genetic engineering in T. ferrooxidans were either not yet developed. Improved techniques are described which will make it easier to construct and analyze the genetic structure and metabolism of recombinant T. ferrooxidans. The metabolism of the model organic sulfur compound dibenzothiophene (DBT) by certain heterotrophic bacteria was confirmed and characterized. Techniques were developed to analyze the metabolites of DBT, so that individual 4S pathway metabolites could be distinguished. These techniques are expected to be valuable when engineering organic sulfur metabolism in Thiobacillus. Strain isolation techniques were used to develop pure cultures of T. ferrooxidans seven of which were assessed as potential recombinant hosts. The mixotrophic strain T. coprinus was also characterized for potential use as an electroporation host. A family of related Thiobacillus plasmids was discovered in the seven strains of P. ferrooxidans mentioned above. One of these plasmids, pTFI91, was cloned into a pUC-based plasmid vector, allowing it to propagate in E. coli. A key portion of the cloned plasmid was sequenced. This segment, which is conserved in all of the related plasmids characterized, contains the vegetative origin of DNA replication, and fortuitously, a novel insertion sequence, designated IS3091. The sequence of the DNA origin revealed that these Thiobacillus plasmids represent a unique class of replicons not previously described. The potentially useful insertion sequence IS3091 was identified as a new member of a previously undefined family of insertion sequences which include the E. coli element IS30.

  10. The redox biology network in cancer pathophysiology and therapeutics

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    Gina Manda

    2015-08-01

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

  11. Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay.

    Science.gov (United States)

    Geng, Xia-Fei; Fang, Min; Liu, Shao-Ping; Li, Yan

    2016-10-01

    This aim of the present study was to investigate clonal growth behavior and analyze the proliferation characteristics of cancer cells. The MCF‑7 human breast cancer cell line, SW480 human colon cancer cell line and SGC7901 human gastric cancer cell line were selected to investigate the morphology of cell clones. Quantum dot‑based molecular targeted imaging techniques (which stained pan‑cytokeratin in the cytoplasm green and Ki67 in the cell nucleus yellow or red) were used to investigate the clone formation rate, cell morphology, discrete tendency, and Ki67 expression and distribution in clones. From the cell clone formation assay, the MCF‑7, SW480 and SGC7901 cells were observed to form clones on days 6, 8 and 12 of cell culture, respectively. These three types of cells had heterogeneous morphology, large nuclear:cytoplasmic ratios, and conspicuous pathological mitotic features. The cells at the clone periphery formed multiple pseudopodium. In certain clones, cancer cells at the borderline were separated from the central cell clusters or presented a discrete tendency. With quantum dot‑based molecular targeted imaging techniques, cells with strong Ki67 expression were predominantly shown to be distributed at the clone periphery, or concentrated on one side of the clones. In conclusion, cancer cell clones showed asymmetric growth behavior, and Ki67 was widely expressed in clones of these three cell lines, with strong expression around the clones, or aggregated at one side. Cell clone formation assay based on quantum dots molecular imaging offered a novel method to study the proliferative features of cancer cells, thus providing a further insight into tumor biology.

  12. TCGA divides gastric cancer into four molecular subtypes:implications for individualized therapeutics

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang

    2014-01-01

    Gastric cancer is a leading cause of cancer deaths in the world. The treatment of gastric cancer is chalenging because of its highly heterogeneous etiology and clinical characteristics. Recent genomic and molecular characterization of gastric cancer, especialy the findings reported by the Cancer Genome Atlas (TCGA), have shed light on the heterogeneity and potential targeted therapeutics for four different subtypes of gastric cancer.

  13. 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.

  14. Dual Roles of IL-27 in Cancer Biology and Immunotherapy

    Science.gov (United States)

    Fabbi, Marina; Carbotti, Grazia

    2017-01-01

    IL-27 is a pleiotropic two-chain cytokine, composed of EBI3 and IL-27p28 subunits, which is structurally related to both IL-12 and IL-6 cytokine families. IL-27 acts through a heterodimer receptor consisting of IL-27Rα (WSX1) and gp130 chains, which mediate signaling predominantly through STAT1 and STAT3. IL-27 was initially reported as an immune-enhancing cytokine that supports CD4+ T cell proliferation, T helper (Th)1 cell differentiation, and IFN-γ production, acting in concert with IL-12. However, subsequent studies demonstrated that IL-27 displays complex immune-regulatory functions, which may result in either proinflammatory or anti-inflammatory effects in relationship to the biological context and experimental models considered. Several pieces of evidence, obtained in preclinical tumor models, indicated that IL-27 has a potent antitumor activity, related not only to the induction of tumor-specific Th1 and cytotoxic T lymphocyte (CTL) responses but also to direct inhibitory effects on tumor cell proliferation, survival, invasiveness, and angiogenic potential. Nonetheless, given its immune-regulatory functions, the effects of IL-27 on cancer may be dual and protumor effects may also occur. Here, we will summarize IL-27 biological activities and its functional overlaps with the IFNs and discuss its dual role in tumors in the light of potential applications to cancer immunotherapy. PMID:28255204

  15. Prediction and testing of biological networks underlying intestinal cancer.

    Directory of Open Access Journals (Sweden)

    Vishal N Patel

    Full Text Available Colorectal cancer progresses through an accumulation of somatic mutations, some of which reside in so-called "driver" genes that provide a growth advantage to the tumor. To identify points of intersection between driver gene pathways, we implemented a network analysis framework using protein interactions to predict likely connections--both precedented and novel--between key driver genes in cancer. We applied the framework to find significant connections between two genes, Apc and Cdkn1a (p21, known to be synergistic in tumorigenesis in mouse models. We then assessed the functional coherence of the resulting Apc-Cdkn1a network by engineering in vivo single node perturbations of the network: mouse models mutated individually at Apc (Apc(1638N+/- or Cdkn1a (Cdkn1a(-/-, followed by measurements of protein and gene expression changes in intestinal epithelial tissue. We hypothesized that if the predicted network is biologically coherent (functional, then the predicted nodes should associate more specifically with dysregulated genes and proteins than stochastically selected genes and proteins. The predicted Apc-Cdkn1a network was significantly perturbed at the mRNA-level by both single gene knockouts, and the predictions were also strongly supported based on physical proximity and mRNA coexpression of proteomic targets. These results support the functional coherence of the proposed Apc-Cdkn1a network and also demonstrate how network-based predictions can be statistically tested using high-throughput biological data.

  16. Scavenger Receptors: Emerging Roles in Cancer Biology and Immunology.

    Science.gov (United States)

    Yu, Xiaofei; Guo, Chunqing; Fisher, Paul B; Subjeck, John R; Wang, Xiang-Yang

    2015-01-01

    Scavenger receptors constitute a large family of evolutionally conserved protein molecules that are structurally and functionally diverse. Although scavenger receptors were originally identified based on their capacity to scavenge modified lipoproteins, these molecules have been shown to recognize and bind to a broad spectrum of ligands, including modified and unmodified host-derived molecules or microbial components. As a major subset of innate pattern recognition receptors, scavenger receptors are mainly expressed on myeloid cells and function in a wide range of biological processes, such as endocytosis, adhesion, lipid transport, antigen presentation, and pathogen clearance. In addition to playing a crucial role in maintenance of host homeostasis, scavenger receptors have been implicated in the pathogenesis of a number of diseases, e.g., atherosclerosis, neurodegeneration, or metabolic disorders. Emerging evidence has begun to reveal these receptor molecules as important regulators of tumor behavior and host immune responses to cancer. This review summarizes our current understanding on the newly identified, distinct functions of scavenger receptors in cancer biology and immunology. The potential of scavenger receptors as diagnostic biomarkers and novel targets for therapeutic interventions to treat malignancies is also highlighted.

  17. Multi-modality molecular imaging for gastric cancer research

    Science.gov (United States)

    Liang, Jimin; Chen, Xueli; Liu, Junting; Hu, Hao; Qu, Xiaochao; Wang, Fu; Nie, Yongzhan

    2011-12-01

    Because of the ability of integrating the strengths of different modalities and providing fully integrated information, multi-modality molecular imaging techniques provide an excellent solution to detecting and diagnosing earlier cancer, which remains difficult to achieve by using the existing techniques. In this paper, we present an overview of our research efforts on the development of the optical imaging-centric multi-modality molecular imaging platform, including the development of the imaging system, reconstruction algorithms and preclinical biomedical applications. Primary biomedical results show that the developed optical imaging-centric multi-modality molecular imaging platform may provide great potential in the preclinical biomedical applications and future clinical translation.

  18. Molecular imaging of cancer using PET and SPECT

    DEFF Research Database (Denmark)

    Kjaer, Andreas

    2006-01-01

    for molecular imaging of cancer. Especially the possibility of a quick transfer of methods developed in animals to patients (translational research) is an important strength. This article will briefly discuss the newest applications and their importance and perspective in relation to the shift in paradigm......Molecular imaging allows for the study of molecular and cellular events in the living intact organism. The nuclear medicine methodologies of positron emission tomography (PET) and single photon emission computer tomography (SPECT) posses several advantages, which make them particularly suited...

  19. Molecular systems biology of Sic1 in yeast cell cycle regulation through multiscale modeling.

    Science.gov (United States)

    Barberis, Matteo

    2012-01-01

    Cell cycle control is highly regulated to guarantee the precise timing of events essential for cell growth, i.e., DNA replication onset and cell division. Failure of this control plays a role in cancer and molecules called cyclin-dependent kinase (Cdk) inhibitors (Ckis) exploit a critical function in cell cycle timing. Here we present a multiscale modeling where experimental and computational studies have been employed to investigate structure, function and temporal dynamics of the Cki Sic1 that regulates cell cycle progression in Saccharomyces cerevisiae. Structural analyses reveal molecular details of the interaction between Sic1 and Cdk/cyclin complexes, and biochemical investigation reveals Sic1 function in analogy to its human counterpart p27(Kip1), whose deregulation leads to failure in timing of kinase activation and, therefore, to cancer. Following these findings, a bottom-up systems biology approach has been developed to characterize modular networks addressing Sic1 regulatory function. Through complementary experimentation and modeling, we suggest a mechanism that underlies Sic1 function in controlling temporal waves of cyclins to ensure correct timing of the phase-specific Cdk activities.

  20. 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.

  1. 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.

  2. The origin, dynamics, and molecular evolution of transmissible cancers

    Directory of Open Access Journals (Sweden)

    Jones EA

    2015-09-01

    Full Text Available Elizabeth A Jones, Yuanyuan Cheng, Katherine BelovFaculty of Veterinary Science, University of Sydney, NSW, AustraliaAbstract: Three transmissible cancers are known to have emerged naturally in the wild: canine transmissible venereal tumor (CTVT; Tasmanian devil facial tumor disease (DFTD; and a recently discovered leukemia-like cancer in soft-shell clams (Mya arenaria. These cancers have all acquired the ability to pass between individuals. DFTD emerged approximately 20 years ago and has decimated the Tasmanian devil population. CTVT arose over 10,000 years ago in an ancient breed of dog. The clam cancer is believed to have evolved at least 40 years ago. In this manuscript, we review CTVT and DFTD, the two transmissible mammalian cancers, and provide an overview of the leukemia-like cancer of clams. We showcase how genetics and genomics have enhanced our understanding of the unique biology, origins, and evolutionary histories of these rare cancers.Keywords: transmissible cancer, devil facial tumor disease, DFTD, canine transmissible venereal tumor, origin, evolution

  3. Molecular genetics of cancer and tumorigenesis: Drosophila models

    Institute of Scientific and Technical Information of China (English)

    Wu-Min Deng

    2011-01-01

    Why do some cells not respond to normal control of cell division and become tumorous? Which signals trigger some tumor cells to migrate and colonize other tissues? What genetic factors are responsible for tumorigenesis and cancer development? What environmental factors play a role in cancer formation and progression? In how many ways can our bodies prevent and restrict the growth of cancerous cells?How can we identify and deliver effective drugs to fight cancer? In the fight against cancer,which kills more people than any other disease,these and other questions have long interested researchers from a diverse range of fields.To answer these questions and to fight cancer more effectively,we must increase our understanding of basic cancer biology.Model organisms,including the fruit fly Drosophila melanogaster,have played instrumental roles in our understanding of this devastating disease and the search for effective cures.Drosophila and its highly effective,easy-touse,and ever-expanding genetic tools have contributed toand enriched our knowledge of cancer and tumor formation tremendously.

  4. Molecular Characterization of Indolent Prostate Cancer

    Science.gov (United States)

    2015-10-01

    Luo, Ph.D. CONTRACTING ORGANIZATION: Johns Hopkins University Baltimore, MD 21218-2680 REPORT DATE: October 2015 TYPE OF REPORT: Annual...DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE Annual Report 3. DATES COVERED 15 Sep 2014- 14 Sep 2015...detected at biopsy , leading to the contemporary problem of prostate cancer over-diagnosis and over-treatment. The objective of the project is to

  5. Miniature and Molecularly Specific Optical Screening Technologies for Breast Cancer

    Science.gov (United States)

    2008-10-01

    and molecular contrast in breast cancer V. Millon SR, Provenzano PP, Elicieri, KW, Brown, JQ, Keely, PJ, Ramanujam, N. "Imaging of ALA-induced PpIX...calculating tissue optical properties. Part I: Theory and validation on synthetic phantoms. Appl Opt, 2006. 45(5): p. 1062-71. 4. Baumann, M., C

  6. Immunophenotyping invasive breast cancer: paving the road for molecular imaging.

    NARCIS (Netherlands)

    Vermeulen, J.F.; Brussel, A.S. van; Groep, P. van der; Morsink, F.H.; Bult, P.; Wall, E. van der; Diest, P.J. van

    2012-01-01

    ABSTRACT: BACKGROUND: Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers m

  7. Molecular prostate cancer pathology: current issues and achievements.

    NARCIS (Netherlands)

    Schalken, J.A.; Bergh, A. von; Bono, A.V.; Foster, C.; Gospadarowicz, M.; Isaacs, W.B.; Rubin, M.; Schroder, F.H.; Tribukait, B.; Tsukamotot, T.; Wiklund, P.

    2005-01-01

    Recent developments in the field of molecular techniques have provided new tools that have led to the discovery of many new promising biomarkers for prostate cancer. These biomarkers may be instrumental in the development of new tests that will have a high specificity for the diagnosis and prognosis

  8. Strengthening cancer biology research, prevention, and control while reducing cancer disparities: student perceptions of a collaborative master's degree program in cancer biology, preventions, and control.

    Science.gov (United States)

    Jillson, I A; Cousin, C E; Blancato, J K

    2013-09-01

    This article provides the findings of a survey of previous and current students in the UDC/GU-LCCC master's degree program. This master's degree program, Cancer Biology, Prevention, and Control is administered and taught jointly by faculty of a Minority Serving Institution, the University of the District of Columbia, and the Lombardi Comprehensive Cancer Center to incorporate the strengths of a community-based school with a research intensive medical center. The program was initiated in 2008 through agreements with both University administrations and funding from the National Cancer Institute. The master's degree program is 36 credits with a focus on coursework in biostatistics, epidemiology, tumor biology, cancer prevention, medical ethics, and cancer outreach program design. For two semesters during the second year, students work full-time with a faculty person on a laboratory or outreach project that is a requirement for graduation. Students are supported and encouraged to transition to a doctoral degree after they obtain the master's and many of them are currently in doctorate programs. Since the inception of the program, 45 students have initiated the course of study, 28 have completed the program, and 13 are currently enrolled in the program. The survey was designed to track the students in their current activities, as well as determine which courses, program enhancements, and research experiences were the least and most useful, and to discern students' perceptions of knowledge acquired on various aspects of Cancer Biology Prevention, and Control Master's Program. Thirty of the 35 individuals to whom email requests were sent responded to the survey, for a response rate of 85.7%. The results of this study will inform the strengthening of the Cancer Biology program by the Education Advisory Committee. They can also be used in the development of comparable collaborative master's degree programs designed to address the significant disparities in prevalence of

  9. Methodologies in cancer cytogenetics and molecular cytogenetics.

    Science.gov (United States)

    Wang, Nancy

    2002-10-30

    Various types of cytogenetic and molecular cytogenetic approaches, including conventional banding, fluorescence in situ hybridization (FISH), fiber-FISH, comparative genomic hybridization (CGH), matrix array CGH, chromosome microdissection, and microcell-mediated chromosome transfer are summarized. The rationale, advantage, and limitations of each approach are discussed with respect to research and clinical applications in human neoplasia.

  10. Molecular Pathways: Isocitrate Dehydrogenase Mutations in Cancer.

    Science.gov (United States)

    Clark, Owen; Yen, Katharine; Mellinghoff, Ingo K

    2016-04-15

    IDH1 and IDH2 are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) and concomitantly produce reduced NADPH from NADP(+) Mutations in the genes encoding IDH1 and IDH2 have recently been found in a variety of human cancers, most commonly glioma, acute myeloid leukemia (AML), chondrosarcoma, and intrahepatic cholangiocarcinoma. The mutant protein loses its normal enzymatic activity and gains a new ability to produce the "oncometabolite" R(-)-2-hydroxyglutarate (R-2-HG). R-2-HG competitively inhibits α-KG-dependent enzymes which play crucial roles in gene regulation and tissue homeostasis. Expression of mutant IDH impairs cellular differentiation in various cell lineages and promotes tumor development in cooperation with other cancer genes. First-generation inhibitors of mutant IDH have entered clinical trials, and have shown encouraging results in patients with IDH-mutant AML. This article summarizes recent progress in our understanding of the role of mutant IDH in tumorigenesis.Clin Cancer Res; 22(8); 1837-42. ©2016 AACR.

  11. 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.

  12. Molecular imaging of cell-mediated cancer immunotherapy.

    Science.gov (United States)

    Lucignani, Giovanni; Ottobrini, Luisa; Martelli, Cristina; Rescigno, Maria; Clerici, Mario

    2006-09-01

    New strategies based on the activation of a patient's immune response are being sought to complement present conventional exogenous cancer therapies. Elucidating the trafficking pathways of immune cells in vivo, together with their migratory properties in relation to their differentiation and activation status, is useful for understanding how the immune system interacts with cancer. Methods based on tissue sampling to monitor immune responses are inadequate for repeatedly characterizing the responses of the immune system in different organs. A solution to this problem might come from molecular and cellular imaging - a branch of biomedical sciences that combines biotechnology and imaging methods to characterize, in vivo, the molecular and cellular processes involved in normal and pathologic states. The general concepts of noninvasive imaging of targeted cells as well as the technology and probes applied to cell-mediated cancer immunotherapy imaging are outlined in this review.

  13. Epigenetic Markers for Molecular Detection of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Vera L. Costa

    2007-01-01

    Full Text Available Prostate cancer is a highly prevalent malignancy, which is clinically silent but curable while organ-confined. Because available screening methods show poor sensitivity and specificity, the development of new molecular markers is warranted. Epigenetic alterations, mainly promoter hypermethylation of cancer-related genes, are common events in prostate cancer and might be used as cancer biomarkers. Moreover, the development of quantitative, high-throughput techniques to assess promoter methylation enabled the simultaneous screening of multiple clinical samples. From the numerous cancer-related genes hypermethylated in prostate cancer only a few proved to be strong candidates to become routine biomarkers. This small set of genes includes GSTP1, APC, RARβ2, Cyclin D2, MDR1, and PTGS2. Single and/or multigene analyses demonstrated the feasibility of detecting early prostate cancer, with high sensitivity and specificity, in body fluids (serum, plasma, urine, and ejaculates and tissue samples. In addition, quantitative hypermethylation of several genes has been associated with clinicopathologic features of tumor aggressiveness, and also reported as independent prognostic factor for relapse. The identification of age-related methylation at specific loci and the differential frequency of methylation among ethnical groups, also provided interesting data linking methylation and prostate cancer risk. Although large trials are needed to validate these findings, the clinical use of these markers might be envisaged for the near future.

  14. Molecular biological character of PRL-3 and its relationship with colorectal cancer metastasis%PRL-3磷酸酶分子生物学特性及其与大肠癌转移

    Institute of Scientific and Technical Information of China (English)

    任萍萍

    2008-01-01

    The phosphatase of regenerating liver(PRL)families of phosphatases,consisting of PRL-1,PRL-2,and PRL-3,are individually overexpressed in a variety of cancer cell lines and tissues when eom-pared with their normal counterparts.Several recent studies have shown that PRL-3 is expressed at a higher lev-el and at a greater frequency in colorectal cancer with liver metastases compared with primary colorectal tumorsand normal colon tissue.Expression of PRL can enhance metastatic and invasive properties of cells and initiate tumor angiogenesis in experimental mice.However,the exact mechanism and in- teracting proteins of the PRL remain unclear.With further study,PRL-3 may server as an attractive target for therapeutic intervention and marker for colon cancer metastasis.%PRL磷酸酶家族含有PRL-1、PRL-2和PRL-3三种分子,每种分子在不同肿瘤谱中都表现为高表达.新近研究发现,与相应正常组织和原发灶相比,PRL-3在大肠癌转移灶中表达水平和表达率明显增高,其表达水平升高与大肠癌的肝转移潜能有一定的相关性.体外大鼠实验PRL-3能显著增强转染细胞的转移、侵袭和血管生成能力.但是PRL-3通过何种机制以及与何种蛋白相互作用促进大肠癌的转移还有待进一步探讨.对PRL-3的深入研究有望使其成为大肠癌转移诊断和治疗的特异靶点.

  15. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    Science.gov (United States)

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research.

  16. Advances of Molecular Targeted Therapy in Squamous Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Li MA

    2013-12-01

    Full Text Available Squamous cell lung cancer (SQCLC is one of the most prevalent subtypes of lung cancer worldwide, about 400,000 persons die from squamous-cell lung cancer around the world, and its pathogenesis is closely linked with tobacco exposure. Unfortunately, squamous-cell lung cancer patients do not benefit from major advances in the development of targeted therapeutics such as epidermal growth factor receptor (EGFR inhibitors or anaplastic lymphoma kinase (ALK inhibitors that show exquisite activity in lungadenocarcinomas with EGFR mutations or echinoderm microtubule associated protein like-4 (EML4-ALK fusions, respectively. Major efforts have been launched to characterize the genomes of squamous-cell lung cancers. Among the new results emanating from these efforts are amplifications of the fibroblast growth factor receptor 1 (FGFR1 gene, the discoidin domain receptor 2 (DDR2 gene mutation as potential novel targets for the treatment of SQCLCs. Researchers find that there are many specific molecular targeted genes in the genome of squamous-cell lung cancer patients. These changes play a vital role in cell cycle regulation, oxidative stress, cell apoptosis, squamous epithelium differentiation, may be the candidate targeted moleculars in SQCLCs. Here, we provide a review on these discoveries and their implications for clinical trials in squamous-cell lungcancer assessing the value of novel therapeutics addressing these targets.

  17. 2012 PLANT MOLECULAR BIOLOGY GORDON RESEARCH CONFERENCE, JULY 15-20, 2012

    Energy Technology Data Exchange (ETDEWEB)

    Sussman, Michael

    2013-07-20

    The 2012 Gordon Conference on Plant Molecular Biology will present cutting-edge research on molecular aspects of plant growth and development, with particular emphasis on recent discoveries in molecular mechanisms involved with plant signaling systems. The Conference will feature a wide range of topics in plant molecular biology including hormone receptors and early events in hormone signaling, plant perception of and response to plant pathogen and symbionts, as well as technological and biological aspects of epigenomics particularly as it relates to signaling systems that regulate plant growth and development. Genomic approaches to plant signaling will be emphasized, including genomic profiling technologies for quantifying various biological subsystems, such as the epigenome, transcriptome, phosphorylome, and metabolome. The meeting will include an important session devoted to answering the question, "What are the biological and technological limits of plant breeding/genetics, and how can they be solved"?

  18. Remaining Mysteries of Molecular Biology: The Role of Polyamines in the Cell.

    Science.gov (United States)

    Miller-Fleming, Leonor; Olin-Sandoval, Viridiana; Campbell, Kate; Ralser, Markus

    2015-10-23

    The polyamines (PAs) spermidine, spermine, putrescine and cadaverine are an essential class of metabolites found throughout all kingdoms of life. In this comprehensive review, we discuss their metabolism, their various intracellular functions and their unusual and conserved regulatory features. These include the regulation of translation via upstream open reading frames, the over-reading of stop codons via ribosomal frameshifting, the existence of an antizyme and an antizyme inhibitor, ubiquitin-independent proteasomal degradation, a complex bi-directional membrane transport system and a unique posttranslational modification-hypusination-that is believed to occur on a single protein only (eIF-5A). Many of these features are broadly conserved indicating that PA metabolism is both concentration critical and evolutionary ancient. When PA metabolism is disrupted, a plethora of cellular processes are affected, including transcription, translation, gene expression regulation, autophagy and stress resistance. As a result, the role of PAs has been associated with cell growth, aging, memory performance, neurodegenerative diseases, metabolic disorders and cancer. Despite comprehensive studies addressing PAs, a unifying concept to interpret their molecular role is missing. The precise biochemical function of polyamines is thus one of the remaining mysteries of molecular cell biology.

  19. Histamine and histamine receptor antagonists in cancer biology.

    Science.gov (United States)

    Blaya, Bruno; Nicolau-Galmés, Francesca; Jangi, Shawkat M; Ortega-Martínez, Idoia; Alonso-Tejerina, Erika; Burgos-Bretones, Juan; Pérez-Yarza, Gorka; Asumendi, Aintzane; Boyano, María D

    2010-07-01

    Histamine has been demonstrated to be involved in cell proliferation, embryonic development, and tumour growth. These various biological effects are mediated through the activation of specific histamine receptors (H1, H2, H3, and H4) that differ in their tissue expression patterns and functions. Although many in vitro and in vivo studies of the modulatory roles of histamine in tumour development and metastasis have been reported, the effect of histamine in the progression of some types of tumours remains controversial; however, recent findings on the role of histamine in the immune system have shed new light on this question. This review focuses on the recent advances in understanding the roles of histamine and its receptors in tumour biology. We report our recent observations of the anti-tumoural effect of H1 histamine antagonists on experimental and human melanomas. We have found that in spite of exogenous histamine stimulated human melanoma cell proliferation, clonogenic ability and migration activity in a dose-dependent manner, the melanoma tumour growth was not modulated by in vivo histamine treatment. On the contrary, terfenadine-treatment in vitro induced melanoma cell death by apoptosis and in vivo terfenadine treatment significantly inhibited tumour growth in murine models. These observations increase our understanding of cancer biology and may inspire novel anticancer therapeutic strategies.

  20. Emerging Molecular and Biological Functions of MBD2, a Reader of DNA Methylation

    Directory of Open Access Journals (Sweden)

    Kathleen H Wood

    2016-05-01

    Full Text Available DNA methylation is an epigenetic mark that is essential for many biological processes and is linked to diseases such as cancer. Methylation is usually associated with transcriptional silencing, but new research has challenged this model. Both transcriptional activation and repression have recently been found to be associated with DNA methylation in a context-specific manner. How DNA methylation patterns are interpreted into different functional output remains poorly understood. One mechanism involves the protein ‘readers’ of methylation, which includes the methyl-CpG binding domain (MBD family of proteins. This review examines the molecular and biological functions of MBD2, which binds to CpG methylation and is an integral part of the nucleosome remodeling and histone deacetylation (NuRD complex. MBD2 has been linked to immune system function and tumorigenesis, yet little is known about its functions in vivo. Recent studies have found the MBD2 protein is ubiquitously expressed, with relatively high levels in the lung, liver and colon. Mbd2 null mice surprisingly show relatively mild phenotypes compared to mice with loss of function of other MBD proteins. This evidence has previously been interpreted as functional redundancy between the MBD proteins. Here we examine and contextualize research that suggests MBD2 has unique properties and functions among the MBD proteins. These functions translate to recently described roles in the development and differentiation of multiple cell lineages, including pluripotent stem cells and various cell types of the immune system, as well as in tumorigenesis. We also consider possible models for the dynamic interactions between MBD2 and NuRD in different tissues in vivo. The functions of MBD2 may have direct therapeutic implications for several areas of human disease, including autoimmune conditions and cancer, in addition to providing insights into the actions of NuRD and chromatin regulation.

  1. Application of Proteomics to Cancer Molecular Diagnostics

    Institute of Scientific and Technical Information of China (English)

    Sam HANASH

    2009-01-01

    @@ Strategies to achieve personalized medicine and improve public health encompass assessment of an individual's risk for disease, early detection and molecular classification of disease resulting in an informed choice of the most appropriate treatment instituted at an early stage of disease develop- ment. A major contribution of proteomics in this field is the development of blood based tests to achieve the goals of personalized medicine.

  2. Molecular Determinants of Hormone Refractory Prostate Cancer

    Science.gov (United States)

    2013-07-01

    to known prostate cancer oncogenes, Never In Mitosis A (NIMA) related kinase 6 (NEK6) reproducibly yielded androgen-independent tumors in female...constitutively active MEK, RAF1, ERBB2, AKT1, PIM1 and PIM2), overexpression of the Never In Mitosis A (NIMA) related kinase 6 (NEK6) reproducibly yielded...Never In Mitosis A (NIMA) related kinase 6 (NEK6), and nemo-like kinase (NLK). Aim 1. Elucidating the role of NIMA-related kinase 6 (NEK6) and nemo

  3. Inter-institutional development of a poster-based cancer biology learning tool.

    Science.gov (United States)

    Andraos-Selim, Cecile; Modzelewski, Ruth A; Steinman, Richard A

    2010-09-01

    There is a paucity of African-American Cancer researchers. To help address this, an educational collaboration was developed between a Comprehensive Cancer Center and a distant undergraduate biology department at a minority institution that sought to teach students introductory cancer biology while modeling research culture. A student-centered active learning curriculum was established that incorporated scientific poster presentations and simulated research exercises to foster learning of cancer biology. Students successfully mined primary literature for supportive data to test cancer-related hypotheses. Student feedback indicated that the poster project substantially enhanced depth of understanding of cancer biology and laid the groundwork for subsequent laboratory work. This inter-institutional collaboration modeled the research process while conveying facts and concepts about cancer.

  4. A perfect time to harness advanced molecular technologies to explore the fundamental biology of Toxocara species.

    Science.gov (United States)

    Gasser, Robin B

    2013-04-15

    Toxocarosis is of major canine health and socioeconomic importance worldwide. Although many studies have given insights into toxocarosis, to date, there has been limited exploration of the molecular biology, biochemistry, genetics, epidemiology and ecology of Toxocara species as well as parasite-host interactions using '-omic' technologies. The present article gives a background on Toxocara species and toxocarosis, describes molecular tools for specific identification and genetic analysis, and provides a prospective view of the benefits that advanced molecular technologies will have towards better understanding the parasites and disease. Tackling key biological questions employing a 'systems biology' approach should lead to new and improved strategies for the treatment, diagnosis and control of toxocarosis.

  5. Telomerase promoter mutations in cancer: an emerging molecular biomarker?

    Science.gov (United States)

    Vinagre, João; Pinto, Vasco; Celestino, Ricardo; Reis, Marta; Pópulo, Helena; Boaventura, Paula; Melo, Miguel; Catarino, Telmo; Lima, Jorge; Lopes, José Manuel; Máximo, Valdemar; Sobrinho-Simões, Manuel; Soares, Paula

    2014-08-01

    Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the "alternative mechanism of telomere lengthening" (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target.

  6. Gastric cancer: a primer on the epidemiology and biology of the disease and an overview of the medical management of advanced disease.

    Science.gov (United States)

    Shah, Manish A; Kelsen, David P

    2010-04-01

    Gastric cancer is a cause of significant morbidity and cancer-related mortality worldwide. Despite recent advances in targeted therapy and understanding of the biology and development of the malignancy, progress in the treatment of gastric cancer has been limited. Most newly diagnosed patients will present with incurable disease, and have a median survival of less than 1 year. Although the disease has widespread ethnic and epidemiologic differences, medical management of gastric cancer does not distinguish among the various disease subtypes. The recent report of the ToGA phase III study has validated Her2 as a molecular target in this disease, supporting the concept that a greater understanding of the biology of gastric cancer subsets may improve treatment selection and overall outcome of individual patients. This article summarizes the epidemiology and ethnic variation of this disease to crystalize subtypes of gastric cancer in the context of current and future medical management of advanced disease.

  7. Multi-study integration of brain cancer transcriptomes reveals organ-level molecular signatures.

    Directory of Open Access Journals (Sweden)

    Jaeyun Sung

    Full Text Available We utilized abundant transcriptomic data for the primary classes of brain cancers to study the feasibility of separating all of these diseases simultaneously based on molecular data alone. These signatures were based on a new method reported herein--Identification of Structured Signatures and Classifiers (ISSAC--that resulted in a brain cancer marker panel of 44 unique genes. Many of these genes have established relevance to the brain cancers examined herein, with others having known roles in cancer biology. Analyses on large-scale data from multiple sources must deal with significant challenges associated with heterogeneity between different published studies, for it was observed that the variation among individual studies often had a larger effect on the transcriptome than did phenotype differences, as is typical. For this reason, we restricted ourselves to studying only cases where we had at least two independent studies performed for each phenotype, and also reprocessed all the raw data from the studies using a unified pre-processing pipeline. We found that learning signatures across multiple datasets greatly enhanced reproducibility and accuracy in predictive performance on truly independent validation sets, even when keeping the size of the training set the same. This was most likely due to the meta-signature encompassing more of the heterogeneity across different sources and conditions, while amplifying signal from the repeated global characteristics of the phenotype. When molecular signatures of brain cancers were constructed from all currently available microarray data, 90% phenotype prediction accuracy, or the accuracy of identifying a particular brain cancer from the background of all phenotypes, was found. Looking forward, we discuss our approach in the context of the eventual development of organ-specific molecular signatures from peripheral fluids such as the blood.

  8. The molecular mechanisms between metabolic syndrome and breast cancer.

    Science.gov (United States)

    Chen, Yi; Wen, Ya-yuan; Li, Zhi-rong; Luo, Dong-lin; Zhang, Xiao-hua

    2016-03-18

    Metabolic syndrome, which is extremely common in developed and some developing countries, is a clustering of at least three of five of the following medical conditions: abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein levels. It has been proved that there is a strong association between metabolic syndrome and breast cancer. Metabolic syndrome could increase the risk of breast cancer and influence the prognosis of the breast cancer patients. Some characteristic of metabolic syndrome such as obesity and lack of physical exercise are all risk factors for developing breast cancer. The metabolic syndrome mainly include obesity, type 2 diabetes, hypercholesterolemia and nonalcoholic fatty liver disease, and each of them impacts the risk of breast cancer and the prognosis of the breast cancer patients in different ways. In this Review, we focus on recently uncovered aspects of the immunological and molecular mechanisms that are responsible for the development of this highly prevalent and serious disease. These studies bring new insight into the complex associations between metabolic syndrome and breast cancer and have led to the development of novel therapeutic strategies that might enable a personalized approach in the management of this disease.

  9. Cyclin E Transgenic Mice: Discovery Tools for Lung Cancer Biology, Therapy, and Prevention

    OpenAIRE

    Freemantle, Sarah J.; Dmitrovsky, Ethan

    2010-01-01

    Lung cancer is the leading cause of cancer-related mortality in the United States and many other countries. This fact underscores the need for clinically relevant models to increase our understanding of lung cancer biology and to help design and implement preventive and more-effective therapeutic interventions for lung cancer. New murine transgenic models of non-small cell lung cancer (NSCLC) have been engineered for this purpose. In one such model, overexpression of the cell-cycle regulator ...

  10. Laboratory techniques in plant molecular biology taught with UniformMu insertion alleles of maize

    Science.gov (United States)

    An undergraduate course - Laboratory Techniques in Plant Molecular Biology - was organized around our research application of UniformMu insertion alleles to investigate mitochondrial functions in plant reproduction. The course objectives were to develop students’ laboratory, record keeping, bioinfor...

  11. Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology (Final Report)

    Science.gov (United States)

    EPA announced the release of the final report, Next Generation Risk Assessment: Incorporation of Recent Advances in Molecular, Computational, and Systems Biology. This report describes new approaches that are faster, less resource intensive, and more robust that can help ...

  12. Molecular damage in cancer: an argument for mTOR-driven aging.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2011-12-01

    Despite common belief, accumulation of molecular damage does not play a key role in aging. Still, cancer (an age-related disease) is initiated by molecular damage. Cancer and aging share a lot in common including the activation of the TOR pathway. But the role of molecular damage distinguishes cancer and aging. Furthermore, an analysis of the role of both damage and aging in cancer argues against "a decline, caused by accumulation of molecular damage" as a cause of aging. I also discuss how random molecular damage, via rounds of multiplication and selection, brings about non-random hallmarks of cancer.

  13. 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.

  14. MicroRNA-regulated networks: the perfect storm for classical molecular biology, the ideal scenario for systems biology.

    Science.gov (United States)

    Vera, Julio; Lai, Xin; Schmitz, Ulf; Wolkenhauer, Olaf

    2013-01-01

    MicroRNAs (miRNAs) are involved in many regulatory pathways some of which are complex networks enriched in regulatory motifs like positive or negative feedback loops or coherent and incoherent feedforward loops. Their complexity makes the understanding of their regulation difficult and the interpretation of experimental data cumbersome. In this book chapter we claim that systems biology is the appropriate approach to investigate the regulation of these miRNA-regulated networks. Systems biology is an interdisciplinary approach by which biomedical questions on biochemical networks are addressed by integrating experiments with mathematical modelling and simulation. We here introduce the foundations of the systems biology approach, the basic theoretical and computational tools used to perform model-based analyses of miRNA-regulated networks and review the scientific literature in systems biology of miRNA regulation, with a focus on cancer.

  15. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    Directory of Open Access Journals (Sweden)

    Vermeulen Jeroen F

    2012-06-01

    Full Text Available Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Methods Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. Results The combination of highly tumor-specific markers glucose transporter 1 (GLUT1, epidermal growth factor receptor (EGFR, insulin-like growth factor-1 receptor (IGF1-R, human epidermal growth factor receptor 2 (HER2, hepatocyte growth factor receptor (MET, and carbonic anhydrase 9 (CAIX 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6 resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. Conclusions In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  16. 2012 CELLULAR & MOLECULAR FUNGAL BIOLOGY GORDON RESEARCH CONFERENCE, JUNE 17 - 22, 2012

    Energy Technology Data Exchange (ETDEWEB)

    Judith Berman

    2012-06-22

    The Gordon Research Conference on CELLULAR & MOLECULAR FUNGAL BIOLOGY was held at Holderness School, Holderness New Hampshire, June 17 - 22, 2012. The 2012 Gordon Conference on Cellular and Molecular Fungal Biology (CMFB) will present the latest, cutting-edge research on the exciting and growing field of molecular and cellular aspects of fungal biology. Topics will range from yeast to filamentous fungi, from model systems to economically important organisms, and from saprophytes and commensals to pathogens of plants and animals. The CMFB conference will feature a wide range of topics including systems biology, cell biology and morphogenesis, organismal interactions, genome organisation and regulation, pathogenesis, energy metabolism, biomass production and population genomics. The Conference was well-attended with 136 participants. Gordon Research Conferences does not permit publication of meeting proceedings.

  17. 2012 Gordon Research Conference on Cellular and Molecular Fungal Biology, Final Progress Report

    Energy Technology Data Exchange (ETDEWEB)

    Berman, Judith [Univ. of Minnesota, Minneapolis, MN (United States)

    2012-06-22

    The Gordon Research Conference on Cellular and Molecular Fungal Biology was held at Holderness School, Holderness New Hampshire, June 17 - 22, 2012. The 2012 Gordon Conference on Cellular and Molecular Fungal Biology (CMFB) will present the latest, cutting-edge research on the exciting and growing field of molecular and cellular aspects of fungal biology. Topics will range from yeast to filamentous fungi, from model systems to economically important organisms, and from saprophytes and commensals to pathogens of plants and animals. The CMFB conference will feature a wide range of topics including systems biology, cell biology and morphogenesis, organismal interactions, genome organisation and regulation, pathogenesis, energy metabolism, biomass production and population genomics. The Conference was well-attended with 136 participants. Gordon Research Conferences does not permit publication of meeting proceedings.

  18. The Transferrin Receptor: A Potential Molecular Imaging Marker for Human Cancer

    Directory of Open Access Journals (Sweden)

    Dagmar Högemann-Savellano

    2003-11-01

    Full Text Available Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors. In the work reported here, investigation into the biology of this receptor using electron microscopy has demonstrated that iron oxide particles targeted to TfR are internalized and accumulate in lysosomal vesicles within cells. Biochemical analysis of the interaction of imaging probes with cells overexpressing the TfR demonstrated that the extent of accumulation, and therefore probe efficacy, is dependent on the nature of the chemical cross-link between transferrin and the iron oxide particle. These data were utilized to design and synthesize an improved imaging probe. Experiments demonstrate that the novel magnetic resonance imaging (MRI probe is sensitive enough to detect small differences in endogenous TfR expression in human cancer cell lines. Quantitative measurement of TfR overexpression in a panel of 27 human breast cancer patients demonstrated that 74% of patient cancer tissues overexpressed the TfR and that the sensitivity of the new imaging agent was suitable to detect TfR overexpression in greater than 40% of these cases. Based on a biochemical and cell biological approach, these studies have resulted in the synthesis and development of an improved MRI probe with the best in vitro and in vivo imaging properties reported to date.

  19. Metastasis promoter S100A4 is a potentially valuable molecular target for cancer therapy.

    Science.gov (United States)

    Sherbet, G V

    2009-07-18

    The growth, invasion and metastatic spread of cancer have been identified with the deregulation of cell proliferation, altered intercellular and cell-substratum adhesion and enhanced motility and the deposition of disseminated cancer cells at distant sites. The identification of therapeutic targets for cancer is crucial to human welfare. Drug development, molecular modelling and design of effective drugs greatly depend upon the identification of suitable therapeutic targets. Several genetic determinants relating to proliferation and growth, invasion and metastasis have been identified. S100A4 appears to be able to activate and integrate pathways to generate the phenotypic responses that are characteristic of cancer. S100A4 signalling can focus on factors associated with normal and aberrant proliferation, apoptosis and growth, and differentiation. It is able to activate signalling pathways leading to the remodelling of the cell membrane and the extracellular matrix; modulation of cytoskeletal dynamics, acquisition of invasiveness and induction of angiogenesis. Therefore S100A4 is arguably a molecular target of considerable potential possessing a wide ranging biological activity that can alter and regulate the major phenotypic features of cancer. The evolution of an appropriate strategy that permits the identification of therapeutic targets most likely to be effective in the disease process without unduly affecting normal biological processes and function is an incontrovertible imperative. By virtue of its ability to activate interacting and multi-functional signalling systems, S100A4 appears to offer suitable targets for developing new therapeutic procedures. Some effectors of the S100A4-activated pathways might also lend themselves as foci of therapeutic interest.

  20. Workshop in computational molecular biology, April 15, 1991--April 14, 1994

    Energy Technology Data Exchange (ETDEWEB)

    Tavare, S.

    1995-04-12

    Funds from this award were used to the Workshop in Computational Molecular Biology, `91 Symposium entitled Interface: Computing Science and Statistics, Seattle, Washington, April 21, 1991; the Workshop in Statistical Issues in Molecular Biology held at Stanford, California, August 8, 1993; and the Session on Population Genetics a part of the 56th Annual Meeting, Institute of Mathematical Statistics, San Francisco, California, August 9, 1993.

  1. Mouse Mammary Tumor Virus Molecular Biology and Oncogenesis

    Directory of Open Access Journals (Sweden)

    Susan R. Ross

    2010-09-01

    Full Text Available Mouse mammary tumor virus (MMTV, which was discovered as a milk‑transmitted, infectious cancer-inducing agent in the 1930s, has been used since that time as an animal model for the study of human breast cancer. Like other complex retroviruses, MMTV encodes a number of accessory proteins that both facilitate infection and affect host immune response. In vivo, the virus predominantly infects lymphocytes and mammary epithelial cells. High level infection of mammary epithelial cells ensures efficient passage of virus to the next generation. It also results in mammary tumor induction, since the MMTV provirus integrates into the mammary epithelial cell genome during viral replication and activates cellular oncogene expression. Thus, mammary tumor induction is a by-product of the infection cycle. A number of important oncogenes have been discovered by carrying out MMTV integration site analysis, some of which may play a role in human breast cancer.

  2. A Biochemistry and Molecular Biology Experiment and Evaluation System for Biotechnology Specialty Students: An Effective Evaluation System to Improve the Biochemistry and Molecular Biology Experiment Teaching

    Science.gov (United States)

    Li, Suxia; Wu, Haizhen; Zhao, Jian; Ou, Ling; Zhang, Yuanxing

    2010-01-01

    In an effort to achieve high success in knowledge and technique acquisition as a whole, a biochemistry and molecular biology experiment was established for high-grade biotechnology specialty students after they had studied essential theory and received proper technique training. The experiment was based on cloning and expression of alkaline…

  3. Molecular epidemiology, cancer-related symptoms, and cytokines pathway.

    Science.gov (United States)

    Reyes-Gibby, Cielito C; Wu, Xifeng; Spitz, Margaret; Kurzrock, Razelle; Fisch, Michael; Bruera, Eduardo; Shete, Sanjay

    2008-08-01

    The Human Genome Project and HapMap have led to a better appreciation of the importance of common genetic variation in determining cancer risk, created potential for predicting response to therapy, and made possible the development of targeted prevention and therapeutic interventions. Advances in molecular epidemiology can be used to explore the role of genetic variation in modulating the risk for severe and persistent symptoms, such as pain, depression, and fatigue, in patients with cancer. The same genes that are implicated in cancer risk might also be involved in the modulation of therapeutic outcomes. For example, polymorphisms in several cytokine genes are potential markers for genetic susceptibility both for cancer risk and for cancer-related symptoms. These genetic polymorphisms are stable markers and easily and reliably assayed to explore the extent to which genetic variation might prove useful in identifying patients with cancer at high-risk of symptom development. Likewise, they could identify subgroups who might benefit most from symptom intervention, and contribute to developing personalized and more effective therapies for persistent symptoms.

  4. AN EPIDEMIOLOGY AND MOLECULAR GENETIC STUDY ON BREAST CANCER SUSCEPTIBILITY

    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征

    2000-01-01

    Objectives. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-based case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel art and Falconer methods were used to analyze the segregation ratio and heritability. Polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significartly, OR is 3.905 ( 95 % CI = 1.079 ~ 14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blood relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LOH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome aberrations were observed. Conclusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

  5. AN EPIDEMIOLOGY AND MOLECULAR GENETIC STUDY ON BREAST CANCER SUSCEPTIBILITY

    Institute of Scientific and Technical Information of China (English)

    贾卫华; 王继先; 李本孝; 李征

    2000-01-01

    Obieaites. To investigate the genetic susceptibility for breast cancer of Chinese, a hospital-besed case-control study, pedigree survey and molecular genetic study were conducted. Methods. Logistic regression model and stratification methods were used in the risk factors analysis. Li-Mantel-Gart and Falconer methods were used to analyze the segregation ratio and heritability. Polymemse chain reaction (PCR) and polyacrylamide gel electrophoresis were used to detect AI, G-banding technique was used to detect the chromosome aberration of peripheral blood lymphocyte. Results. Family history of breast cancer is related to enhanced breast cancer risk significantly, OR is 3.905(95% CI = 1.079—14.13), and it widely interacts with other risk factors. Accumulative incidence of breast cancer in first degree relatives is 9.99%, which is larger than that in second, third degree and non-blnod relatives. Segregation ratio is 0.021, heritability among first degree relatives is 35.6 ± 5.8%. Frequencies of LDH at BRCA1 and BRCA2 loci in sporadic breast cancer are 6.12% and 5.77% respectively. In the sibs, both of them show LOH at D13S173 locus, and high frequencies of chromosome abermtions were observed.Condusions. Genetic susceptibility contributes to breast cancer occurrence of Chinese, and its racial variation may be one of the important reasons for the large difference of incidence between western and eastern countries.

  6. 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

  7. 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

  8. Summary of the primer on tumor immunology and the biological therapy of cancer

    OpenAIRE

    Margolin Kim; Liu Shujuan; Li Yufeng; Hwu Patrick

    2009-01-01

    Abstract The International Society for Biological Therapy of Cancer (iSBTc) is one of the "premier destinations for interaction and innovation in the cancer biologics community". It provides a primer course each year during the annual meeting to address the most important areas of tumor immunology and immunotherapy. The course has been given by prominent investigators in the area of interest, covering the core principles of cancer immunology and immunotherapy. The target audience for this pro...

  9. From Gene to Protein: A 3-Week Intensive Course in Molecular Biology for Physical Scientists

    Science.gov (United States)

    Nadeau, Jay L.

    2009-01-01

    This article describes a 3-week intensive molecular biology methods course based upon fluorescent proteins, which is successfully taught at the McGill University to advanced undergraduates and graduates in physics, chemical engineering, biomedical engineering, and medicine. No previous knowledge of biological terminology or methods is expected, so…

  10. Molecular biology and its applications in orthodontics and oral and maxillofacial surgery

    NARCIS (Netherlands)

    Ren, Yjin

    2005-01-01

    : Molecular biology is an exciting, rapidly expanding field, which has enabled enormously greater understanding of the biology of diseases and malfunctions in many fields. It chiefly concerns itself with understanding the interactions between the various systems of a cell, including the interrelatio

  11. Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

    OpenAIRE

    Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S; Zhang, Yan-Bing; Zi, Xiaolin

    2014-01-01

    There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reacti...

  12. Dissecting the Biology of Menstrual Cycle-Associated Breast Cancer Risk

    Science.gov (United States)

    Atashgaran, Vahid; Wrin, Joseph; Barry, Simon Charles; Dasari, Pallave; Ingman, Wendy V.

    2016-01-01

    Fluctuations in circulating estrogen and progesterone across the menstrual cycle lead to increased breast cancer susceptibility in women; however, the biological basis for this increased risk is not well understood. Estrogen and progesterone have important roles in normal mammary gland development, where they direct dynamic interactions among the hormonally regulated mammary epithelial, stromal, and immune cell compartments. The continuous fluctuations of estrogen and progesterone over a woman’s reproductive lifetime affect the turnover of mammary epithelium, stem cells, and the extracellular matrix, as well as regulate the phenotype and function of mammary stromal and immune cells, including macrophages and regulatory T cells. Collectively, these events may result in genome instability, increase the chance of random genetic mutations, dampen immune surveillance, and promote tolerance in the mammary gland, and thereby increase the risk of breast cancer initiation. This article reviews the current status of our understanding of the molecular and the cellular changes that occur in the mammary gland across the menstrual cycle and how continuous menstrual cycling may increase breast cancer susceptibility in women. PMID:28083513

  13. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    Science.gov (United States)

    Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew; Register, Janna; Vo-Dinh, Tuan

    2015-08-01

    Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS) exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), as well as nanoprobes for photoacoustic tomography (PAT), two-photon photoluminescence (TPL) and surface-enhanced Raman spectroscopy (SERS). Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

  14. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yang eLiu

    2015-08-01

    Full Text Available Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT, magnetic resonance imaging (MRI, positron emission tomography (PET, as well as nanoprobes for photoacoustic tomography (PAT, two-photon photoluminescence (TPL and surface-enhanced Raman spectroscopy (SERS. Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

  15. Molecular Mechanism Underlying Lymphatic Metastasis in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Zhiwen Xiao

    2014-01-01

    Full Text Available As the most challenging human malignancies, pancreatic cancer is characterized by its insidious symptoms, low rate of surgical resection, high risk of local invasion, metastasis and recurrence, and overall dismal prognosis. Lymphatic metastasis, above all, is recognized as an early adverse event in progression of pancreatic cancer and has been described to be an independent poor prognostic factor. It should be noted that the occurrence of lymphatic metastasis is not a casual or stochastic but an ineluctable and designed event. Increasing evidences suggest that metastasis-initiating cells (MICs and the microenvironments may act as a double-reed style in this crime. However, the exact mechanisms on how they function synergistically for this dismal clinical course remain largely elusive. Therefore, a better understanding of its molecular and cellular mechanisms involved in pancreatic lymphatic metastasis is urgently required. In this review, we will summarize the latest advances on lymphatic metastasis in pancreatic cancer.

  16. Multiple breast cancer cell-lines derived from a single tumor differ in their molecular characteristics and tumorigenic potential.

    Directory of Open Access Journals (Sweden)

    Goar Mosoyan

    Full Text Available BACKGROUND: Breast cancer cell lines are widely used tools to investigate breast cancer biology and to develop new therapies. Breast cancer tissue contains molecularly heterogeneous cell populations. Thus, it is important to understand which cell lines best represent the primary tumor and have similarly diverse phenotype. Here, we describe the development of five breast cancer cell lines from a single patient's breast cancer tissue. We characterize the molecular profiles, tumorigenicity and metastatic ability in vivo of all five cell lines and compare their responsiveness to 4-hydroxytamoxifen (4-OHT treatment. METHODS: Five breast cancer cell lines were derived from a single patient's primary breast cancer tissue. Expression of different antigens including HER2, estrogen receptor (ER, CK8/18, CD44 and CD24 was determined by flow cytometry, western blotting and immunohistochemistry (IHC. In addition, a Fluorescent In Situ Hybridization (FISH assay for HER2 gene amplification and p53 genotyping was performed on all cell lines. A xenograft model in nude mice was utilized to assess the tumorigenic and metastatic abilities of the breast cancer cells. RESULTS: We have isolated, cloned and established five new breast cancer cell lines with different tumorigenicity and metastatic abilities from a single primary breast cancer. Although all the cell lines expressed low levels of ER, their growth was estrogen-independent and all had high-levels of expression of mutated non-functional p53. The HER2 gene was rearranged in all cell lines. Low doses of 4-OHT induced proliferation of these breast cancer cell lines. CONCLUSIONS: All five breast cancer cell lines have different antigenic expression profiles, tumorigenicity and organ specific metastatic abilities although they derive from a single tumor. None of the studied markers correlated with tumorigenic potential. These new cell lines could serve as a model for detailed genomic and proteomic analyses to

  17. Sensitive force technique to probe molecular adhesion and structural linkages at biological interfaces.

    OpenAIRE

    Evans, E; Ritchie, K; Merkel, R.

    1995-01-01

    Adhesion and cytoskeletal structure are intimately related in biological cell function. Even with the vast amount of biological and biochemical data that exist, little is known at the molecular level about physical mechanisms involved in attachments between cells or about consequences of adhesion on the material structure. To expose physical actions at soft biological interfaces, we have combined an ultrasensitive transducer and reflection interference microscopy to image submicroscopic displ...

  18. Tangible Models and Haptic Representations Aid Learning of Molecular Biology Concepts

    Science.gov (United States)

    Johannes, Kristen; Powers, Jacklyn; Couper, Lisa; Silberglitt, Matt; Davenport, Jodi

    2016-01-01

    Can novel 3D models help students develop a deeper understanding of core concepts in molecular biology? We adapted 3D molecular models, developed by scientists, for use in high school science classrooms. The models accurately represent the structural and functional properties of complex DNA and Virus molecules, and provide visual and haptic…

  19. Features of Knowledge Building in Biology: Understanding Undergraduate Students' Ideas about Molecular Mechanisms

    Science.gov (United States)

    Southard, Katelyn; Wince, Tyler; Meddleton, Shanice; Bolger, Molly S.

    2016-01-01

    Research has suggested that teaching and learning in molecular and cellular biology (MCB) is difficult. We used a new lens to understand undergraduate reasoning about molecular mechanisms: the knowledge-integration approach to conceptual change. Knowledge integration is the dynamic process by which learners acquire new ideas, develop connections…

  20. A Model of How Different Biology Experts Explain Molecular and Cellular Mechanisms

    Science.gov (United States)

    Trujillo, Caleb M.; Anderson, Trevor R.; Pelaez, Nancy J.

    2015-01-01

    Constructing explanations is an essential skill for all science learners. The goal of this project was to model the key components of expert explanation of molecular and cellular mechanisms. As such, we asked: What is an appropriate model of the components of explanation used by biology experts to explain molecular and cellular mechanisms? Do…