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  1. Molecular profiles of screen detected vs. symptomatic breast cancer and their impact on survival: results from a clinical series

    International Nuclear Information System (INIS)

    Crispo, Anna; Esposito, Emanuela; Amore, Alfonso; Di Bonito, Maurizio; Botti, Gerardo; Montella, Maurizio; Barba, Maddalena; D’Aiuto, Giuseppe; De Laurentiis, Michelino; Grimaldi, Maria; Rinaldo, Massimo; Caolo, Giuseppina; D’Aiuto, Massimiliano; Capasso, Immacolata

    2013-01-01

    Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit. In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes. Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05). Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially. Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology

  2. Molecular series-tunneling junctions.

    Science.gov (United States)

    Liao, Kung-Ching; Hsu, Liang-Yan; Bowers, Carleen M; Rabitz, Herschel; Whitesides, George M

    2015-05-13

    Charge transport through junctions consisting of insulating molecular units is a quantum phenomenon that cannot be described adequately by classical circuit laws. This paper explores tunneling current densities in self-assembled monolayer (SAM)-based junctions with the structure Ag(TS)/O2C-R1-R2-H//Ga2O3/EGaIn, where Ag(TS) is template-stripped silver and EGaIn is the eutectic alloy of gallium and indium; R1 and R2 refer to two classes of insulating molecular units-(CH2)n and (C6H4)m-that are connected in series and have different tunneling decay constants in the Simmons equation. These junctions can be analyzed as a form of series-tunneling junctions based on the observation that permuting the order of R1 and R2 in the junction does not alter the overall rate of charge transport. By using the Ag/O2C interface, this system decouples the highest occupied molecular orbital (HOMO, which is localized on the carboxylate group) from strong interactions with the R1 and R2 units. The differences in rates of tunneling are thus determined by the electronic structure of the groups R1 and R2; these differences are not influenced by the order of R1 and R2 in the SAM. In an electrical potential model that rationalizes this observation, R1 and R2 contribute independently to the height of the barrier. This model explicitly assumes that contributions to rates of tunneling from the Ag(TS)/O2C and H//Ga2O3 interfaces are constant across the series examined. The current density of these series-tunneling junctions can be described by J(V) = J0(V) exp(-β1d1 - β2d2), where J(V) is the current density (A/cm(2)) at applied voltage V and βi and di are the parameters describing the attenuation of the tunneling current through a rectangular tunneling barrier, with width d and a height related to the attenuation factor β.

  3. Molecular biology of gastric cancer.

    Science.gov (United States)

    Cervantes, A; Rodríguez Braun, E; Pérez Fidalgo, A; Chirivella González, I

    2007-04-01

    Despite its decreasing incidence overall, gastric cancer is still a challenging disease. Therapy is based mainly upon surgical resection when the tumour remains localised in the stomach. Conventional chemotherapy may play a role in treating micrometastatic disease and is effective as palliative therapy for recurrent or advanced disease. However, the knowledge of molecular pathways implicated in gastric cancer pathogenesis is still in its infancy and the contribution of molecular biology to the development of new targeted therapies in gastric cancer is far behind other more common cancers such as breast, colon or lung. This review will focus first on the difference of two well defined types of gastric cancer: intestinal and diffuse. A discussion of the cell of origin of gastric cancer with some intriguing data implicating bone marrow derived cells will follow, and a comprehensive review of different genetic alterations detected in gastric cancer, underlining those that may have clinical, therapeutic or prognostic implications.

  4. Strategy to find molecular signatures in a small series of rare cancers: validation for radiation-induced breast and thyroid tumors.

    Directory of Open Access Journals (Sweden)

    Nicolas Ugolin

    Full Text Available Methods of classification using transcriptome analysis for case-by-case tumor diagnosis could be limited by tumor heterogeneity and masked information in the gene expression profiles, especially as the number of tumors is small. We propose a new strategy, EMts_2PCA, based on: 1 The identification of a gene expression signature with a great potential for discriminating subgroups of tumors (EMts stage, which includes: a a learning step, based on an expectation-maximization (EM algorithm, to select sets of candidate genes whose expressions discriminate two subgroups, b a training step to select from the sets of candidate genes those with the highest potential to classify training tumors, c the compilation of genes selected during the training step, and standardization of their levels of expression to finalize the signature. 2 The predictive classification of independent prospective tumors, according to the two subgroups of interest, by the definition of a validation space based on a two-step principal component analysis (2PCA. The present method was evaluated by classifying three series of tumors and its robustness, in terms of tumor clustering and prediction, was further compared with that of three classification methods (Gene expression bar code, Top-scoring pair(s and a PCA-based method. Results showed that EMts_2PCA was very efficient in tumor classification and prediction, with scores always better that those obtained by the most common methods of tumor clustering. Specifically, EMts_2PCA permitted identification of highly discriminating molecular signatures to differentiate post-Chernobyl thyroid or post-radiotherapy breast tumors from their sporadic counterparts that were previously unsuccessfully classified or classified with errors.

  5. Cancer Stratification by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Justus Weber

    2015-03-01

    Full Text Available The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2. Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter, as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers.

  6. Molecular imaging in cervical cancer

    International Nuclear Information System (INIS)

    KHAN, Sairah R.; ROCKALL, Andrea G.; BARWICK, Tara D.

    2016-01-01

    Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed.

  7. Breast Cancer Molecular Subtypes Among Moroccan Women

    Directory of Open Access Journals (Sweden)

    Wissal Mahir

    2016-12-01

    Full Text Available Introduction: Breast cancer remains despite the therapeutic progress, the leading cause of death by cancer among women. It represents a group of very heterogeneous clinical, histopathological and molecular diseases. Molecular heterogeneity has been demonstrated by genomic analysis, even for similar histology cancers. Four subgroups of breast carcinomas are distinguished: Luminal A, Luminal B, HER2 over expression and Basal - like. The Immuno-histo-chemical analysis useip (estrogen receptors RE, the PR (progesterone receptors, the ((Human Epidermal Growth Factor Receptor-2, the Ki67 (proliferation marker HER2, CK5/6 has shown a subdivision into subgroups similar to those found by genomic analysis. These subgroups are different from the point of view of clinical course and response to adjuvant treatment.Objectives: The aim of this work is to study the molecular profile of the breast cancers by immunostaining on Moroccan series to a classification with a prognostic value allowing a treatment tailored to each group of patients. Furthermore, the molecular subgroups were correlated to other clinical and histological factors.Material and methods: It is a prospective study of the laboratory of Anatomy and Pathologic cytology of the children's Hospital, the service I of the maternity hospital in Rabat and in cooperation with the United Nations Centre of pathological anatomy. To do this, 88 cases of breast cancer together were diagnosed between January 1, 2010 and December 31, 2014, taking a period of five years. All tissue samples made subject study of Immuno-histo-chemistry with the following markers: RE, PR, HER2 and Ki67. Only negative triple cases (HR and HER2 negative benefited from an additional marking with CK5/6 and EGFR to set the basal profile.Results: Series of 88 cases of mammary carcinomas observed on operating parts, ranged in age between 28 and 84 years old, with an average of 51 ± 12, 8. Carcinoma infiltrating non-specific (DOCTORS was

  8. Molecular genetics of breast cancer

    International Nuclear Information System (INIS)

    Radice, P.; Pierotti, M. A.

    1997-01-01

    In the last two decades, molecular studies have enlightened the complexity of the genetic alterations that occur in breast cancer cells. To date, more than 40 different genes or loci have been found to be altered in breast carcinomas. Although some of these genes, as for example ERBB2, appear to be mutated in a high proportion of cases, their mechanism of action and their role in the different stages of cancer development are still poorly understood. More recently, two major determinants of the inherited predisposition to breast cancer, BRCA1 and BRCA2, have been isolated. As a consequence, it is now possible to screen families with a positive history of breast carcinomas for the identification of mutations carriers, in order to address these individuals into adequate programs of cancer surveillance and prevention

  9. Molecular Testing for Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Hye Seung Lee

    2017-03-01

    Full Text Available 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.

  10. Molecular biology of pancreatic cancer.

    Science.gov (United States)

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

    2011-06-28

    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 mole melanoma, and Peutz-Jeghers and Lynch syndromes. 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.

  11. 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.

  12. Molecular pathogenesis and mechanisms of thyroid cancer

    Science.gov (United States)

    Xing, Mingzhao

    2013-01-01

    Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. PMID:23429735

  13. Molecular pathology of prostate cancer.

    Science.gov (United States)

    Cazares, L H; Drake, R R; Esquela-Kirscher, A; Lance, R S; Semmes, O J; Troyer, D A

    2010-01-01

    This chapter includes discussion of the molecular pathology of tissue, blood, urine, and expressed prostatic secretions. Because we are unable to reliably image the disease in vivo, a 12 core method that oversamples the peripheral zone is widely used. This generates large numbers of cores that need to be carefully processed and sampled. In spite of the large number of tissue cores, the amount of tumor available for study is often quite limited. This is a particular challenge for research, as new biomarker assays will need to preserve tissue architecture intact for histopathology. Methods of processing and reporting pathology are discussed. With the exception of ductal variants, recognized subtypes of prostate cancer are largely confined to research applications, and most prostate cancers are acinar. Biomarker discovery in urine and expressed prostatic secretions would be useful since these are readily obtained and are proximate fluids. The well-known challenges of biomarker discovery in blood and urine are referenced and discussed. Mediators of carcinogenesis can serve as biomarkers as exemplified by mutations in PTEN and TMPRSS2:ERG fusion. The use of proteomics in biomarker discovery with an emphasis on imaging mass spectroscopy of tissues is discussed. Small RNAs are of great interest, however, their usefulness as biomarkers in clinical decision making remains the subject of ongoing research. The chapter concludes with an overview of blood biomarkers such as circulating nucleic acids and tumor cells and bound/free isoforms of prostate specific antigen (PSA).

  14. Molecular Cancer Prevention: Current Status & Future Directions

    Science.gov (United States)

    Maresso, Karen Colbert; Tsai, Kenneth Y.; Brown, Powel H.; Szabo, Eva; Lippman, Scott; Hawk, Ernest

    2016-01-01

    The heterogeneity and complexity of advanced cancers strongly supports the rationale for an enhanced focus on molecular prevention as a priority strategy to reduce the burden of cancer. Molecular prevention encompasses traditional chemopreventive agents as well as vaccinations and therapeutic approaches to cancer-predisposing conditions. Despite challenges to the field, we now have refined insights into cancer etiology and early pathogenesis; successful risk assessment and new risk models; agents with broad preventive efficacy (e.g., aspirin) in common chronic diseases, including cancer; and a successful track record of more than 10 agents approved by the FDA for the treatment of precancerous lesions or cancer risk reduction. The development of molecular preventive agents does not differ significantly from the development of therapies for advanced cancers, yet has unique challenges and special considerations given that it most often involves healthy or asymptomatic individuals. Agents, biomarkers, cohorts, overall design, and endpoints are key determinants of molecular preventive trials, as with therapeutic trials, although distinctions exist for each within the preventive setting. Progress in the development and evolution of molecular preventive agents has been steadier in some organ systems, such as breast and skin, than in others. In order for molecular prevention to be fully realized as an effective strategy, a number of challenges to the field must be addressed. Here we provide a brief overview of the context for and special considerations of molecular prevention along with a discussion of the results of major randomized controlled trials. PMID:26284997

  15. Cancer molecular markers: A guide to cancer detection and management.

    Science.gov (United States)

    Nair, Meera; Sandhu, Sardul Singh; Sharma, Anil Kumar

    2018-02-08

    Cancer is generally caused by the molecular alterations which lead to specific mutations. Advances in molecular biology have provided an impetus to the study of cancers with valuable prognostic and predictive significance. Over the hindsight various attempts have been undertaken by scientists worldwide, in the management of cancer; where, we have witnessed a number of molecular markers which allow the early detection of cancers and lead to a decrease in its mortality rate. Recent advances in oncology have led to the discovery of cancer markers that has allowed early detection and targeted therapy of tumors. In this context, current review provides a detail outlook on various molecular markers for diagnosis, prognosis and management of therapeutic response in cancer patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. 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

  17. Molecular Classification and Correlates in Colorectal Cancer

    OpenAIRE

    Ogino, Shuji; Goel, Ajay

    2008-01-01

    Molecular classification of colorectal cancer is evolving. As our understanding of colorectal carcinogenesis improves, we are incorporating new knowledge into the classification system. In particular, global genomic status [microsatellite instability (MSI) status and chromosomal instability (CIN) status] and epigenomic status [CpG island methylator phenotype (CIMP) status] play a significant role in determining clinical, pathological and biological characteristics of colorectal cancer. In thi...

  18. Molecular biology of bladder cancer.

    Science.gov (United States)

    Martin-Doyle, William; Kwiatkowski, David J

    2015-04-01

    Classic as well as more recent large-scale genomic analyses have uncovered multiple genes and pathways important for bladder cancer development. Genes involved in cell-cycle control, chromatin regulation, and receptor tyrosine and PI3 kinase-mammalian target of rapamycin signaling pathways are commonly mutated in muscle-invasive bladder cancer. Expression-based analyses have identified distinct types of bladder cancer that are similar to subsets of breast cancer, and have prognostic and therapeutic significance. These observations are leading to novel therapeutic approaches in bladder cancer, providing optimism for therapeutic progress. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Facing Forward Series: Life After Cancer Treatment

    Science.gov (United States)

    ... treatment Coping with your feelings Going back to work and relating with friends and coworkers Show this booklet to the people who are close to you so they understand what life is like after cancer treatment. Take it with ...

  20. Stars in Nutrition and Cancer Lecture Series | Division of Cancer Prevention

    Science.gov (United States)

    This lecture series features extraordinary contributors or "stars" in the field of cancer and nutrition research. Speakers highlight the important role that nutrition plays in modifying cancer development. Past lectures are videotaped and available for viewing. |

  1. Radionuclide molecular target therapy for lung cancer

    International Nuclear Information System (INIS)

    Zhang Fuhai; Meng Zhaowei; Tan Jian

    2012-01-01

    Lung cancer harms people's health or even lives severely. Currently, the morbidity and mortality of lung cancer are ascending all over the world. Accounting for 38.08% of malignant tumor caused death in male and 16% in female in cities,ranking top in both sex. Especially, the therapy of non-small cell lung cancer has not been obviously improved for many years. Recently, sodium/iodide transporter gene transfection and the therapy of molecular target drugs mediated radionuclide are being taken into account and become the new research directions in treatment of advanced lung cancer patients with the development of technology and theory for medical molecular biology and the new knowledge of lung cancer's pathogenesis. (authors)

  2. Molecular biology of the lung cancer

    International Nuclear Information System (INIS)

    Panov, S.Z.

    2005-01-01

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

  3. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  4. [The molecular biology of epithelial ovarian cancer].

    Science.gov (United States)

    Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

    2012-12-01

    Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.

  5. Molecular perspectives in differentiated thyroid cancer.

    Science.gov (United States)

    Buffet, C; Groussin, L

    2015-02-01

    Progress in understanding the molecular genetics of thyroid cancer in the last 20 years has accelerated recently with the advent of high-throughput sequencing technologies known as Next-Generation Sequencing. Besides classical molecular abnormalities involving the MAPK (Mitogen Activated Protein Kinase) and PI3K (PhosphoInositide 3-Kinase) pathways that play a key role in follicular-derived thyroid tumorigenesis, new molecular abnormalities have been discovered. The major advances in recent years have been the discovery of new somatic driver gene point mutations (such as RASAL1 [RAS protein activator Like 1] mutations in follicular cancer) and/or mutations that have prognostic value (such as TERT [Telomerase reverse transcriptase] promoter mutations); new chromosomal rearrangements, usually having close connection with exposure to ionizing radiation (such as ALK [Anaplastic Lymphoma Kinase] rearrangements); and deregulation of some gene or microRNA expression representing a molecular signature. Progress made in understanding the molecular mechanisms of thyroid cancer offers new perspectives for the diagnosis of the benign or malignant status of a thyroid nodule, to refine prognosis and offer new perspectives of targeted therapy for radioiodine-refractory cancers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. [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.

  7. Molecular targets in serous gynecologic cancers

    NARCIS (Netherlands)

    Groeneweg, J.W.

    2015-01-01

    In this thesis we describe a series of studies assessing the effectiveness of targeted therapeutics that inhibit Notch signaling or the HER2 receptor in serous gynecologic cancers. In the first part of the thesis, we have confirmed previous data by showing expression of Notch1 and Notch3 in ovarian

  8. Molecular and biological interactions in colorectal cancer

    NARCIS (Netherlands)

    Heer, Pieter de

    2007-01-01

    The current thesis discusses the use of molecular and biological tumor markers to predict clinical outcome. By studying several key processes in the develepment of cancer as regulation of cell motility (non-receptor protein tyrosin adesion kinases, FAK, Src and paxillin, Apoptosis (caspase-3

  9. Challenging the Cancer Molecular Stratification Dogma: Intratumoral Heterogeneity Undermines Consensus Molecular Subtypes and Potential Diagnostic Value in Colorectal Cancer.

    Science.gov (United States)

    Dunne, Philip D; McArt, Darragh G; Bradley, Conor A; O'Reilly, Paul G; Barrett, Helen L; Cummins, Robert; O'Grady, Tony; Arthur, Ken; Loughrey, Maurice B; Allen, Wendy L; McDade, Simon S; Waugh, David J; Hamilton, Peter W; Longley, Daniel B; Kay, Elaine W; Johnston, Patrick G; Lawler, Mark; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra

    2016-08-15

    A number of independent gene expression profiling studies have identified transcriptional subtypes in colorectal cancer with potential diagnostic utility, culminating in publication of a colorectal cancer Consensus Molecular Subtype classification. The worst prognostic subtype has been defined by genes associated with stem-like biology. Recently, it has been shown that the majority of genes associated with this poor prognostic group are stromal derived. We investigated the potential for tumor misclassification into multiple diagnostic subgroups based on tumoral region sampled. We performed multiregion tissue RNA extraction/transcriptomic analysis using colorectal-specific arrays on invasive front, central tumor, and lymph node regions selected from tissue samples from 25 colorectal cancer patients. We identified a consensus 30-gene list, which represents the intratumoral heterogeneity within a cohort of primary colorectal cancer tumors. Using a series of online datasets, we showed that this gene list displays prognostic potential HR = 2.914 (confidence interval 0.9286-9.162) in stage II/III colorectal cancer patients, but in addition, we demonstrated that these genes are stromal derived, challenging the assumption that poor prognosis tumors with stem-like biology have undergone a widespread epithelial-mesenchymal transition. Most importantly, we showed that patients can be simultaneously classified into multiple diagnostically relevant subgroups based purely on the tumoral region analyzed. Gene expression profiles derived from the nonmalignant stromal region can influence assignment of colorectal cancer transcriptional subtypes, questioning the current molecular classification dogma and highlighting the need to consider pathology sampling region and degree of stromal infiltration when employing transcription-based classifiers to underpin clinical decision making in colorectal cancer. Clin Cancer Res; 22(16); 4095-104. ©2016 AACRSee related commentary by Morris and

  10. Molecular markers for thyroid cancer

    International Nuclear Information System (INIS)

    Marrero Rodriguez, Maria Teresa; Sinconegui Gomez, Belkys; Cruz Cruz, Anaisa

    2015-01-01

    The importance of the study of the thyroid nodule lies in excluding the possibility of a malignant lesion because the majority of lesions are benign but there is a malignancy risk of 5 to 10%. Most of them are well differentiated carcinomas originating in the follicular epithelium. In spite of the fact that the majority are benign lesions, distinguishing them from carcinomas is crucial to treatment and adequate follow-up. Fine-needle biopsy allows making the diagnosis in most of cases. However, this method is restricted, particularly when diagnosing follicular lesions. In an effort to improve the diagnostic accuracy of biopsy and to provide new diagnosing criteria, a number of molecular markers have been put forward, some of which has wide range of approval whereas others still awaits to be validated for further implementation. This article presented an updated review of molecular markers with higher number of evidence, more accessible and potentially usable from a methodological viewpoint for diagnosis of the thyroid nodule before surgery. The importance of the study of the thyroid nodule lies in excluding the possibility of a malignant lesion because the majority of lesions are benign but there is a malignancy risk of 5 to 10%. Most of them are well differentiated carcinomas originating in the follicular epithelium. In spite of the fact that the majority are benign lesions, distinguishing them from carcinomas is crucial to treatment and adequate follow-up. Fine-needle biopsy allows making the diagnosis in most of cases. However, this method is restricted, particularly when diagnosing follicular lesions. In an effort to improve the diagnostic accuracy of biopsy and to provide new diagnosing criteria, a number of molecular markers have been put forward, some of which has wide range of approval whereas others still awaits to be validated for further implementation. This article presented an updated review of molecular markers with higher number of evidence, more

  11. Molecular Cochaperones: Tumor Growth and Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Stuart K. Calderwood

    2013-01-01

    Full Text Available Molecular chaperones play important roles in all cellular organisms by maintaining the proteome in an optimally folded state. They appear to be at a premium in cancer cells whose evolution along the malignant pathways requires the fostering of cohorts of mutant proteins that are employed to overcome tumor suppressive regulation. To function at significant rates in cells, HSPs interact with cochaperones, proteins that assist in catalyzing individual steps in molecular chaperoning as well as in posttranslational modification and intracellular localization. We review current knowledge regarding the roles of chaperones such as heat shock protein 90 (Hsp90 and Hsp70 and their cochaperones in cancer. Cochaperones are potential targets for cancer therapy in themselves and can be used to assess the likely prognosis of individual malignancies. Hsp70 cochaperones Bag1, Bag3, and Hop play significant roles in the etiology of some cancers as do Hsp90 cochaperones Aha1, p23, Cdc37, and FKBP1. Others such as the J domain protein family, HspBP1, TTC4, and FKBPL appear to be associated with more benign tumor phenotypes. The key importance of cochaperones for many pathways of protein folding in cancer suggests high promise for the future development of novel pharmaceutical agents.

  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. Molecular biology of prostate cancer progression

    International Nuclear Information System (INIS)

    Thompson, Timothy C.; Sehgal, I.; Timme, T.L.; Rn, C.; Yang, G.; Park, S.H.

    1996-01-01

    'control' gene in human prostate cancer was supported by studies using molecular biological and immunohistochemical techniques (Eastham et al, Clin Cancer Res 1:1111-1118, 1995 and Yang et al, Clin Cancer Res 2:399-401, 1996). Another possible ''control'' gene related to prostate cancer metastases may be the gene which encodes TGF-β1. We have previously shown that overexpression of TGF-β1 is associated with mouse and human prostate cancer and occurs predominantly in metastatic disease (Eastham et al, Lab Invest 73:628-635, 1995). To investigate a possible role of TGF-β1 in metastatic progression, we compared growth and extracellular matrix responses to TGF-β1 in six metastatic and six primary tumor cell lines derived from our metastatic mouse prostate cancer model system. The results indicated that tumor cell lines derived from focal pulmonary metastases secrete greater quantities of total TGF-β's and have lost most or all TGF-β1 growth inhibition, but respond to TGF-β1 through induction of type IV collagenase, matrix metalloproteinase-9. Cell lines derived from primary site tumors retain TGF-β1 growth inhibition, but lack TGF-β1-induced collagenase activity. Our results indicate that the elimination and/or subversion of TGF-β1 responsive pathways should be considered a mechanistic framework for metastatic events (Sehgal et al., Cancer Res 56:3359-3365, 1996). Both p53 and TGF-β1 can regulate the expression of downstream genetic targets, therefore, we are currently pursuing a strategy using differential display-polymerase chain reaction to elucidate additional changes in gene expression resulting from loss and/or subversion of function for these two putative ''control'' genes in prostate cancer metastasis. Hopefully, identification of these target genes will lead to greater understanding of the mechanisms of prostate cancer metastasis and possibly provide novel therapeutic targets

  14. Molecular cytogenetic in the familial cancers

    International Nuclear Information System (INIS)

    Cermak, M.

    2015-01-01

    The development of cancer diseases is accompanied by number of genetic changes at different levels of the genome. Some of these changes are still subject of research but others are already known in such an extent that they are associated with a specific type of malignity, the development, or treatment possibilities. The cancer genetics dispose of wide range of techniques, with reliable detection of the causal changes. Starting the molecular cytogenetics has launched a new era in diagnostics of genetic aberrations. Fluorescence in situ hybridization (FISH) definitely changed cytogenetic world from black and white to color one and set the foundation of modern investigative methods such as M-FISH, CGH, array CGH and many others. Successively all these methodologies have become a part of routine cancer diagnostics thorough the world. Actually, when much attention is given mostly to submicroscopic changes in DNA supposed as predispositions to various malignancies, the molecular cytogenetics is trying to success in competition of modern highly sensitive molecular biology methods. (author)

  15. Molecular targeted therapies of aggressive thyroid cancer

    Directory of Open Access Journals (Sweden)

    Silvia Martina eFerrari

    2015-11-01

    Full Text Available Differentiated thyroid carcinomas (DTC that arise from follicular cells account > 90% of thyroid cancer (TC [papillary thyroid cancer (PTC 90%, follicular thyroid cancer (FTC 10%], while medullary thyroid cancer (MTC accounts < 5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts towards the development of new drugs.Several genetic alterations in different molecular pathways in TC have been shown in the last decades, associated with TC development and progression. Rearranged during transfection (RET/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the above-mentioned molecular pathways involved in growth, angiogenesis, local and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC and anaplastic thyroid cancer (ATC, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds, and to personalize

  16. Molecular concept in human oral cancer.

    Science.gov (United States)

    Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U S

    2015-01-01

    The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of proto-oncogenes/oncogenes and tumor suppressor genes. Furthermore, these gene alterations can deregulate the normal activity such as increase in the production of growth factors (transforming growth factor-α [TGF-α], TGF-β, platelet-derived growth factor, etc.) or numbers of cell surface receptors (epidermal growth factor receptor, G-protein-coupled receptor, etc.), enhanced intracellular messenger signaling and mutated production of transcription factors (ras gene family, c-myc gene) which results disturb to tightly regulated signaling pathways of normal cell. Several oncogenes and tumor suppressor genes have been implicated in oral cancer especially cyclin family, ras, PRAD-1, cyclin-dependent kinase inhibitors, p53 and RB1. Viral infections, particularly with oncogenic human papilloma virus subtype (16 and 18) and Epstein-Barr virus have tumorigenic effect on oral epithelia. Worldwide, this is an urgent need to initiate oral cancer research programs at molecular and genetic level which investigates the causes of genetic and molecular defect, responsible for malignancy. This approach may lead to development of target dependent tumor-specific drugs and appropriate gene therapy.

  17. Molecularly targeted drugs for metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Cheng YD

    2013-11-01

    Full Text Available Ying-dong Cheng, Hua Yang, Guo-qing Chen, Zhi-cao Zhang Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China Abstract: The survival rate of patients with metastatic colorectal cancer (mCRC has significantly improved with applications of molecularly targeted drugs, such as bevacizumab, and led to a substantial improvement in the overall survival rate. These drugs are capable of specifically targeting the inherent abnormal pathways in cancer cells, which are potentially less toxic than traditional nonselective chemotherapeutics. In this review, the recent clinical information about molecularly targeted therapy for mCRC is summarized, with specific focus on several of the US Food and Drug Administration-approved molecularly targeted drugs for the treatment of mCRC in the clinic. Progression-free and overall survival in patients with mCRC was improved greatly by the addition of bevacizumab and/or cetuximab to standard chemotherapy, in either first- or second-line treatment. Aflibercept has been used in combination with folinic acid (leucovorin–fluorouracil–irinotecan (FOLFIRI chemotherapy in mCRC patients and among patients with mCRC with wild-type KRAS, the outcomes were significantly improved by panitumumab in combination with folinic acid (leucovorin–fluorouracil–oxaliplatin (FOLFOX or FOLFIRI. Because of the new preliminary studies, it has been recommended that regorafenib be used with FOLFOX or FOLFIRI as first- or second-line treatment of mCRC chemotherapy. In summary, an era of new opportunities has been opened for treatment of mCRC and/or other malignancies, resulting from the discovery of new selective targeting drugs. Keywords: metastatic colorectal cancer (mCRC, antiangiogenic drug, bevacizumab, aflibercept, regorafenib, cetuximab, panitumumab, clinical trial, molecularly targeted therapy

  18. Prognostic molecular markers in early breast cancer

    International Nuclear Information System (INIS)

    Esteva, Francisco J; Hortobagyi, Gabriel N

    2004-01-01

    A multitude of molecules involved in breast cancer biology have been studied as potential prognostic markers. In the present review we discuss the role of established molecular markers, as well as potential applications of emerging new technologies. Those molecules used routinely to make treatment decisions in patients with early-stage breast cancer include markers of proliferation (e.g. Ki-67), hormone receptors, and the human epidermal growth factor receptor 2. Tumor markers shown to have prognostic value but not used routinely include cyclin D 1 and cyclin E, urokinase-like plasminogen activator/plasminogen activator inhibitor, and cathepsin D. The level of evidence for other molecular markers is lower, in part because most studies were retrospective and not adequately powered, making their findings unsuitable for choosing treatments for individual patients. Gene microarrays have been successfuly used to classify breast cancers into subtypes with specific gene expression profiles and to evaluate prognosis. RT-PCR has also been used to evaluate expression of multiple genes in archival tissue. Proteomics technologies are in development

  19. Molecular imaging of apoptosis in cancer

    International Nuclear Information System (INIS)

    Hakumaeki, Juhana M.; Liimatainen, Timo

    2005-01-01

    Apoptosis plays an important role in cancer. Mechanisms hindering its action are implicated in a number of malignancies. Also, the induction of apoptosis plays a pivotal role in non-surgical cancer treatment regimes such as irradiation, chemotherapy, or hormones. Recent advanced in imaging science have made it now possible for us to detect and visualize previously inaccessible and even unrecognized biological phenomena in cells and tissue undergoing apoptosis in vivo. Not only are these imaging techniques painting an intriguing picture of the spatiotemporal characteristics and metabolic and biophysical of apoptosis in situ, but they are expected to have an ever increasing impact in preclinical testing and design of new anticancer agents as well. Rapid and accurate visualization of apoptotic response in the clinical settings can also be of significant diagnostic and prognostic worth. With the advent of molecular medicine and patient-tailored treatment options and therapeutic agents, such monitoring techniques are becoming paramount

  20. 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.

  1. 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.

  2. Apoptosis and Molecular Targeting Therapy in Cancer

    Science.gov (United States)

    Hassan, Mohamed; Watari, Hidemichi; AbuAlmaaty, Ali; Ohba, Yusuke; Sakuragi, Noriaki

    2014-01-01

    Apoptosis is the programmed cell death which maintains the healthy survival/death balance in metazoan cells. Defect in apoptosis can cause cancer or autoimmunity, while enhanced apoptosis may cause degenerative diseases. The apoptotic signals contribute into safeguarding the genomic integrity while defective apoptosis may promote carcinogenesis. The apoptotic signals are complicated and they are regulated at several levels. The signals of carcinogenesis modulate the central control points of the apoptotic pathways, including inhibitor of apoptosis (IAP) proteins and FLICE-inhibitory protein (c-FLIP). The tumor cells may use some of several molecular mechanisms to suppress apoptosis and acquire resistance to apoptotic agents, for example, by the expression of antiapoptotic proteins such as Bcl-2 or by the downregulation or mutation of proapoptotic proteins such as BAX. In this review, we provide the main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells. We discuss how carcinogenesis could be developed via defective apoptotic pathways or their convergence. We listed some molecules which could be targeted to stimulate apoptosis in different cancers. Together, we briefly discuss the development of some promising cancer treatment strategies which target apoptotic inhibitors including Bcl-2 family proteins, IAPs, and c-FLIP for apoptosis induction. PMID:25013758

  3. Molecular pathways and therapeutic targets in lung cancer

    Science.gov (United States)

    Shtivelman, Emma; Hensing, Thomas; Simon, George R.; Dennis, Phillip A.; Otterson, Gregory A.; Bueno, Raphael; Salgia, Ravi

    2014-01-01

    Lung cancer is still the leading cause of cancer death worldwide. Both histologically and molecularly lung cancer is heterogeneous. This review summarizes the current knowledge of the pathways involved in the various types of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. It describes the major pathways and molecular alterations implicated in the development and progression of non-small cell lung cancer (adenocarcinoma and squamous cancer), and of small cell carcinoma, emphasizing the molecular alterations comprising the specific blueprints in each group. The approved and investigational targeted therapies as well as the immune therapies, and clinical trials exploring the variety of targeted approaches to treatment of lung cancer are the main focus of this review. PMID:24722523

  4. Progress in molecular-based management of differentiated thyroid cancer

    Science.gov (United States)

    Xing, Mingzhao; Haugen, Bryan R; Schlumberger, Martin

    2014-01-01

    Substantial developments have occurred in the past 5–10 years in clinical translational research of thyroid cancer. Diagnostic molecular markers, such as RET-PTC, RAS, and BRAFV600E mutations; galectin 3; and a new gene expression classifier, are outstanding examples that have improved diagnosis of thyroid nodules. BRAF mutation is a prognostic genetic marker that has improved risk stratification and hence tailored management of patients with thyroid cancer, including those with conventionally low risks. Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid cancers as shown in clinical trials; such treatments are likely to become a component of the standard treatment regimen for patients with thyroid cancer in the near future. These novel molecular-based management strategies for thyroid nodules and thyroid cancer are the most exciting developments in this unprecedented era of molecular thyroid-cancer medicine. PMID:23668556

  5. Unexplained Drownings and the Cardiac Channelopathies: A Molecular Autopsy Series

    Science.gov (United States)

    Tester, David J.; Medeiros-Domingo, Argelia; Will, Melissa L.; Ackerman, Michael J.

    2011-01-01

    OBJECTIVE: To determine the prevalence and spectrum of mutations associated with long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) in a seemingly unexplained drowning cohort. PATIENTS AND METHODS: From September 1, 1998, through October 31, 2010, 35 unexplained drowning victims (23 male and 12 female; mean ± SD age, 17±12 years [range, 4-69 years]) were referred for a cardiac channel molecular autopsy. Of these, 28 (20 male and 8 female) drowned while swimming, and 7 (3 male and 4 female) were bathtub submersions. Polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing were used for a comprehensive mutational analysis of the 3 major LQTS-susceptibility genes (KCNQ1, KCNH2, and SCN5A), and a targeted analysis of the CPVT1-associated, RYR2-encoded cardiac ryanodine receptor was conducted. RESULTS: Of the 28 victims of swimming-related drowning, 8 (28.6%) were mutation positive, including 2 with KCNQ1 mutations (L273F, AAPdel71-73 plus V524G) and 6 with RYR2 mutations (R414C, I419F, R1013Q, V2321A, R2401H, and V2475F). None of the bathtub victims were mutation positive. Of the 28 victims who drowned while swimming, women were more likely to be mutation positive than men (5/8 [62.5%] vs 3/20 [15%]; P=.02). Although none of the mutation-positive, swimming-related drowning victims had a premortem diagnosis of LQTS or CPVT, a family history of cardiac arrest, family history of prior drowning, or QT prolongation was present in 50%. CONCLUSION: Nearly 30% of the victims of swimming-related drowning hosted a cardiac channel mutation. Genetic testing should be considered in the postmortem evaluation of an unexplained drowning, especially if a positive personal or family history is elicited. PMID:21964171

  6. Molecular targeted therapy for advanced gastric cancer.

    Science.gov (United States)

    Kim, Jong Gwang

    2013-03-01

    Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration; the median survival is approximately 7 to 11 months, and survival at 2 years is exceptionally > 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, many molecular targeting agents have been evaluated in international randomized studies, and trastuzumab, an anti-HER-2 monoclonal antibody, has shown antitumor activity against HER-2-positive AGC. However, this benefit is limited to only ~20% of patients with AGC (patients with HER-2-positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of molecular predictive and prognostic markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies.

  7. A review of molecular biomarkers for bladder cancer | Miakhil ...

    African Journals Online (AJOL)

    Background: Numerous molecular markers for bladder cancer have been identified and investigated with various laboratory techniques. Molecular markers are isolated from tissue, serum and urine. They fall into proteomic, genetic and epigenetic categories. Some of molecular markers show promising results in terms of ...

  8. Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives

    Directory of Open Access Journals (Sweden)

    Yoon Young Choi

    2016-01-01

    Full Text Available Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus–positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

  9. Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives.

    Science.gov (United States)

    Choi, Yoon Young; Noh, Sung Hoon; Cheong, Jae-Ho

    2016-01-01

    Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus-positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

  10. Self-renewal molecular mechanisms of colorectal cancer stem cells

    OpenAIRE

    Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

    2016-01-01

    Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth facto...

  11. Inflammation to cancer: The molecular biology in the pancreas (Review)

    OpenAIRE

    LING, SUNBIN; FENG, TINGTING; JIA, KAIQI; TIAN, YU; LI, YAN

    2014-01-01

    Inflammatory responses are known to be correlated with cancer initiation and progression, and exploration of the route from inflammation to cancer makes a great contribution in elucidating the mechanisms underlying cancer development. Pancreatic cancer (PC) is a lethal disease with a low radical-resection rate and a poor prognosis. As chronic pancreatitis is considered to be a significant etiological factor for PC development, the current review aims to describe the molecular pathways from in...

  12. Molecular Mechanisms Linking Exercise to Cancer Prevention and Treatment

    DEFF Research Database (Denmark)

    Hojman, Pernille; Gehl, Julie; Christensen, Jesper F.

    2018-01-01

    The benefits of exercise training for cancer patients are becoming increasingly evident. Physical exercise has been shown to reduce cancer incidence and inhibit tumor growth. Here we provide the status of the current molecular understanding of the effect of exercise on cancer. We propose...... that exercise has a role in controlling cancer progression through a direct effect on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of anti-cancer treatment efficacy. These findings have wide-ranging societal implications......, as this understanding may lead to changes in cancer treatment strategies. Hojman et al. discuss the role of exercise in controlling cancer progression through direct effects on tumor-intrinsic factors, interplay with whole-body exercise effects, alleviation of cancer-related adverse events, and improvement of cancer...

  13. Personalized Cancer Medicine: Molecular Diagnostics, Predictive biomarkers, and Drug Resistance

    Science.gov (United States)

    Gonzalez de Castro, D; Clarke, P A; Al-Lazikani, B; Workman, P

    2013-01-01

    The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution. PMID:23361103

  14. Ovarian cancer: Novel molecular aspects for clinical assessment.

    Science.gov (United States)

    Palmirotta, Raffaele; Silvestris, Erica; D'Oronzo, Stella; Cardascia, Angela; Silvestris, Franco

    2017-09-01

    Ovarian cancer is a very heterogeneous tumor which has been traditionally characterized according to the different histological subtypes and differentiation degree. In recent years, innovative molecular screening biotechnologies have allowed to identify further subtypes of this cancer based on gene expression profiles, mutational features, and epigenetic factors. These novel classification systems emphasizing the molecular signatures within the broad spectrum of ovarian cancer have not only allowed a more precise prognostic prediction, but also proper therapeutic strategies for specific subgroups of patients. The bulk of available scientific data and the high refinement of molecular classifications of ovarian cancers can today address the research towards innovative drugs with the adoption of targeted therapies tailored for single molecular profiles leading to a better prediction of therapeutic response. Here, we summarize the current state of knowledge on the molecular bases of ovarian cancer, from the description of its molecular subtypes derived from wide high-throughput analyses to the latest discoveries of the ovarian cancer stem cells. The latest personalized treatment options are also presented with recent advances in using PARP inhibitors, anti-angiogenic, anti-folate receptor and anti-cancer stem cells treatment approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Molecular basis of the triple negative breast cancer

    Directory of Open Access Journals (Sweden)

    Ayse Feyda Nursal

    2015-06-01

    Full Text Available Breast cancer is the most common type of cancer in women and more than 1 million breast cancer cases are diagnosed each year all over the world. Breast cancer is a complex and heterogeneous disease in terms of its molecular structure, mutation type, metastase properties, clinical course and therapeutic response. Breast cancer is divided into subtypes based on expression properties of molecular markers as estrogen receptor, progestron receptor, human epidermal growth factor receptor 2. Triple-negative breast cancer is characterized by the lack of tumors that estrogen receptor, progestron receptor, human epidermal growth factor receptor 2 gene expression. These type of tumors lead to agressive clinical course due to unresponsiveness to systemic endocrine therapy and poor prognosis. Triple negative breast cancer constitutes 10-20% of all breast cancers. It affects generally young and African-American women. Triple negative breast cancer have several subtypes based on the gene expression properties. The majority of them are basal-like breast cancers. In this review, current literature is revised and summarized with respect to the molecular basis of triple negative cancers. [Archives Medical Review Journal 2015; 24(2.000: 251-259

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

    International Nuclear Information System (INIS)

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

    2000-01-01

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

  17. Early Detection of Breast Cancer Using Molecular Beacons

    National Research Council Canada - National Science Library

    Yang, Lily

    2008-01-01

    .... We proposed to use molecular beacon technology to detect the level of expression of several biomarker genes that are highly expressed in breast cancer cells but not in normal breast epithelial cells...

  18. Introduction to the cellular and molecular biology of cancer

    National Research Council Canada - National Science Library

    Selby, P. (Peter); Knowles, Margaret A

    2005-01-01

    ... A. Prigent 186xii CONTENTS 12 Apoptosis: molecular physiology and significance for cancer therapeutics Dean A. Fennell 210 13 Mechanisms of viral carcinogenesis Paul Farrell 229 14 Cytokines and canc...

  19. Molecular Imaging and Precision Medicine in Head and Neck Cancer.

    Science.gov (United States)

    Mena, Esther; Thippsandra, Shwetha; Yanamadala, Anusha; Redy, Siddaling; Pattanayak, Puskar; Subramaniam, Rathan M

    2017-01-01

    The concept of using tumor genomic profiling information has revolutionized personalized cancer treatment. Head and neck (HN) cancer management is being influenced by recent discoveries of activating mutations in epidermal growth factor receptor and related targeted therapies with tyrosine kinase inhibitors, targeted therapies for Kristen Rat Sarcoma, and MET proto-oncogenes. Molecular imaging using PET plays an important role in assessing the biologic behavior of HN cancer with the goal of delivering individualized cancer treatment. This review summarizes recent genomic discoveries in HN cancer and their implications for functional PET imaging in assessing response to targeted therapies, and drug resistance mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Molecular concept in human oral cancer

    OpenAIRE

    Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U. S.

    2015-01-01

    The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in...

  1. Molecular Determinants of Hormone Refractory Prostate Cancer

    Science.gov (United States)

    2017-07-01

    receptor is no longer essential for survival, collectively termed androgen pathway independent prostate cancer (APIPC) (Nelson, 2012). A subset of these...Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer . Cancer Cell. 2011 May 17;19(5):575-86. Chen J, Li...2005a). The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer . Part 1: Modifications to the androgen receptor

  2. Integrated Molecular Imaging and Therapy for Breast Cancer

    National Research Council Canada - National Science Library

    Panchapakesan, Balaji

    2008-01-01

    ...) and NIR dosing of cancer cells using SWCNT. While previous studies have shown the transport of DNA into cells using nanotubes, in this study we show multi-component molecular targeting of both IGF1R and Her2 surface markers in cancer cells...

  3. Molecular taxonomy provides new insights into anopheles species of the neotropical arribalzagia series.

    Directory of Open Access Journals (Sweden)

    Giovan F Gómez

    Full Text Available Phylogenetic analysis of partial mitochondrial cytochrome oxidase c subunit I (COI and nuclear internal transcribed spacer 2 (ITS2 sequences were used to evaluate initial identification and to investigate phylogenetic relationships of seven Anopheles morphospecies of the Arribalzagia Series from Colombia. Phylogenetic trees recovered highly supported clades for An. punctimaculas.s., An. calderoni, An. malefactor s.l., An. neomaculipalpus, An. apicimacula s.l., An. mattogrossensis and An. peryassui. This study provides the first molecular confirmation of An. malefactorfrom Colombia and discovered conflicting patterns of divergence for the molecular markers among specimens from northeast and northern Colombia suggesting the presence of two previously unrecognized Molecular Operational Taxonomic Units (MOTUs. Furthermore, two highly differentiated An. apicimacula MOTUs previously found in Panama were detected. Overall, the combined molecular dataset facilitated the detection of known and new Colombian evolutionary lineages, and constitutes the baseline for future research on their bionomics, ecology and potential role as malaria vectors.

  4. Screening for breast cancer in a high-risk series

    International Nuclear Information System (INIS)

    Woodard, E.D.; Hempelmann, L.H.; Janus, J.; Logan, W.; Dean, P.

    1982-01-01

    A unique cohort of women at increased risk of breast cancer because of prior X-ray treatment of acute mastitis and their selected high-risk siblings were offered periodic breast cancer screening including physical examination of the breasts, mammography, and thermography. Twelve breast cancers were detected when fewer than four would have been expected based on age-specific breast cancer detection rates from the National Cancer institute/American Cancer Society Breast Cancer Demonstration Detection Projects. Mammograpy was positive in all cases but physical examination was positive in only three cases. Thermography was an unreliable indicator of disease. Given the concern over radiation-induced risk, use of low-dose technique and of criteria for participation that select women at high risk of breast cancer will maximize the benefit/risk ratio for mammography screening

  5. Variable contact gap single-molecule conductance determination for a series of conjugated molecular bridges

    DEFF Research Database (Denmark)

    Haiss, W.; Wang, Christian; Jitchati, R.

    2008-01-01

    It is now becoming clear that the characteristics of the whole junction are important in determining the conductance of single molecules bound between two metal contacts. This paper shows through measurements on a series of seven conjugated molecular bridges that contact separation is an importan...... that conductance increases rather dramatically at higher tilt angle away from the normal for conformationally rigid molecular wires and that this increase in conductance arises from increased electronic coupling between the molecular bridge and the gold contacts.......It is now becoming clear that the characteristics of the whole junction are important in determining the conductance of single molecules bound between two metal contacts. This paper shows through measurements on a series of seven conjugated molecular bridges that contact separation is an important......-distance curves and knowledge of the terminal to terminal length of the molecular wire. The contact gap separation dependence is interpreted as arising from tilting of these molecules in the junction and this model is underpinned by ab initio transport computations. In this respect we make the general observation...

  6. Molecular imaging in the framework of personalized cancer medicine.

    Science.gov (United States)

    Belkić, Dzevad; Belkić, Karen

    2013-11-01

    With our increased understanding of cancer cell biology, molecular imaging offers a strategic bridge to oncology. This complements anatomic imaging, particularly magnetic resonance (MR) imaging, which is sensitive but not specific. Among the potential harms of false positive findings is lowered adherence to recommended surveillance post-therapy and by persons at increased cancer risk. Positron emission tomography (PET) plus computerized tomography (CT) is the molecular imaging modality most widely used in oncology. In up to 40% of cases, PET-CT leads to changes in therapeutic management. Newer PET tracers can detect tumor hypoxia, bone metastases in androgen-sensitive prostate cancer, and human epidermal growth factor receptor type 2 (HER2)-expressive tumors. Magnetic resonance spectroscopy provides insight into several metabolites at the same time. Combined with MRI, this yields magnetic resonance spectroscopic imaging (MRSI), which does not entail ionizing radiation and is thus suitable for repeated monitoring. Using advanced signal processing, quantitative information can be gleaned about molecular markers of brain, breast, prostate and other cancers. Radiation oncology has benefited from molecular imaging via PET-CT and MRSI. Advanced mathematical approaches can improve dose planning in stereotactic radiosurgery, stereotactic body radiotherapy and high dose-rate brachytherapy. Molecular imaging will likely impact profoundly on clinical decision making in oncology. Molecular imaging via MR could facilitate early detection especially in persons at high risk for specific cancers.

  7. Molecular Concordance Between Primary Breast Cancer and Matched Metastases

    DEFF Research Database (Denmark)

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

    2016-01-01

    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....... 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......, 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...

  8. [Molecular Biology for Surgical Treatment of Lung Cancer].

    Science.gov (United States)

    Suda, Kenichi; Mitsudomi, Tetsuya

    2017-01-01

    Progress in lung cancer research achieved during the last 10 years was summarized. These include identification of novel driver mutations and application of targeted therapies, resistance mechanisms to targeted therapies, and immunotherapy with immune checkpoint inhibitors. Molecular biology also affects the field of surgical treatment. Several molecular markers have been reported to predict benign/ malignant or stable/growing tumors, although far from clinical application. In perioperative period, there is a possibility of atrial natriuretic peptide to prevent cancer metastasis. As adjuvant settings, although biomarker-based cytotoxic therapies failed to show clinical efficacy, several trials are ongoing employing molecular targeted agents (EGFR-TKI or ALK-TKI) or immune checkpoint inhibitors. In clinical practice, mutational information is sometimes used to distinguish 2nd primary tumors from pulmonary metastases of previous cancers. Surgery also has important role for oligo-progressive disease during molecular targeted therapies.

  9. 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. © 2015 Society for Endocrinology.

  10. Prostate Cancer Detection by Molecular Urinalysis

    Science.gov (United States)

    2011-04-01

    subjected to physical manipulation, thus creating the potential for their non- invasive detection in either urine or expressed prostatic fluid ( EPF ...samples or EPF . The recent application of molecular techniques to the study of PC has led to the identification of several novel molecular alterations...focused on detecting such molecular changes in the urine or EPF [7-12,15]. Paralleling the advances in biomarker discovery, sig- nificant advances in

  11. Molecular Biomarkers in the Clinical Management of Prostate Cancer.

    Science.gov (United States)

    Udager, Aaron M; Tomlins, Scott A

    2018-01-08

    Prostate cancer, one of the most common noncutaneous malignancies in men, is a heterogeneous disease with variable clinical outcome. Although the majority of patients harbor indolent tumors that are essentially cured by local therapy, subsets of patients present with aggressive disease or recur/progress after primary treatment. With this in mind, modern clinical approaches to prostate cancer emphasize the need to reduce overdiagnosis and overtreatment via personalized medicine. Advances in our understanding of prostate cancer pathogenesis, coupled with recent technologic innovations, have facilitated the development and validation of numerous molecular biomarkers, representing a range of macromolecules assayed from a variety of patient sample types, to help guide the clinical management of prostate cancer, including early detection, diagnosis, prognostication, and targeted therapeutic selection. Herein, we review the current state of the art regarding prostate cancer molecular biomarkers, emphasizing those with demonstrated utility in clinical practice. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  12. Self-renewal molecular mechanisms of colorectal cancer stem cells.

    Science.gov (United States)

    Pan, Tianhui; Xu, Jinghong; Zhu, Yongliang

    2017-01-01

    Colorectal cancer stem cells (CCSCs) represent a small fraction of the colorectal cancer cell population that possess self-renewal and multi-lineage differentiation potential and drive tumorigenicity. Self-renewal is essential for the malignant biological behaviors of colorectal cancer stem cells. While the self-renewal molecular mechanisms of colorectal cancer stem cells are not yet fully understood, the aberrant activation of signaling pathways, such as Wnt, Notch, transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) and Hedgehog-Gli (HH-GLI), specific roles mediated by cell surface markers and micro-environmental factors are involved in the regulation of self-renewal. The elucidation of the molecular mechanisms behind self-renewal may lead to the development of novel targeted interventions for the treatment of colorectal cancer.

  13. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George L

    2006-01-01

    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC) therapy. 1...

  14. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George

    2003-01-01

    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive therapy. Methods: 1...

  15. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George L

    2004-01-01

    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive therapy. Methods: 1...

  16. Colorectal Cancers: An Update on Their Molecular Pathology.

    Science.gov (United States)

    Inamura, Kentaro

    2018-01-20

    Colorectal cancers (CRCs) are the third leading cause of cancer-related mortality worldwide. Rather than being a single, uniform disease type, accumulating evidence suggests that CRCs comprise a group of molecularly heterogeneous diseases that are characterized by a range of genomic and epigenomic alterations. This heterogeneity slows the development of molecular-targeted therapy as a form of precision medicine. Recent data regarding comprehensive molecular characterizations and molecular pathological examinations of CRCs have increased our understanding of the genomic and epigenomic landscapes of CRCs, which has enabled CRCs to be reclassified into biologically and clinically meaningful subtypes. The increased knowledge of the molecular pathological epidemiology of CRCs has permitted their evolution from a vaguely understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes, a development that will allow the implementation of personalized therapies and better management of patients with CRC. This review provides a perspective regarding recent developments in our knowledge of the molecular and epidemiological landscapes of CRCs, including results of comprehensive molecular characterizations obtained from high-throughput analyses and the latest developments regarding their molecular pathologies, immunological biomarkers, and associated gut microbiome. Advances in our understanding of potential personalized therapies for molecularly specific subtypes are also reviewed.

  17. Molecular mechanisms of cisplatin resistance in cervical cancer.

    Science.gov (United States)

    Zhu, Haiyan; Luo, Hui; Zhang, Wenwen; Shen, Zhaojun; Hu, Xiaoli; Zhu, Xueqiong

    2016-01-01

    Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%-20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer.

  18. [Molecular biology of castration-resistant prostate cancer].

    Science.gov (United States)

    Doucet, Ludovic; Terrisse, Safae; Gauthier, Hélène; Pouessel, Damien; Le Maignan, Christine; Teixeira, Luis; Culine, Stéphane

    2015-06-01

    Castration-resistant prostate cancer was subjected to a paradigm switch from hormone resistance to androgen deprivation therapy resistance during the last decade. Indeed, new therapeutics targeting the androgen receptor showed clinical efficacy in patients with progressive disease under castration. Thus, it is a proof that the AR remains a dominant driver of oncogenesis in earlier-called hormone resistant prostate cancer. This review summarizes the molecular mechanisms involved in castration-resistant prostate cancer. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  19. Inflammation to cancer: The molecular biology in the pancreas (Review).

    Science.gov (United States)

    Ling, Sunbin; Feng, Tingting; Jia, Kaiqi; Tian, Yu; Li, Yan

    2014-06-01

    Inflammatory responses are known to be correlated with cancer initiation and progression, and exploration of the route from inflammation to cancer makes a great contribution in elucidating the mechanisms underlying cancer development. Pancreatic cancer (PC) is a lethal disease with a low radical-resection rate and a poor prognosis. As chronic pancreatitis is considered to be a significant etiological factor for PC development, the current review aims to describe the molecular pathways from inflammation to pancreatic carcinogenesis, in support of the strategies for the prevention, diagnosis and treatment of PC.

  20. Molecular Imaging and Precision Medicine in Prostate Cancer.

    Science.gov (United States)

    Ceci, Francesco; Fiorentino, Michelangelo; Castellucci, Paolo; Fanti, Stefano

    2017-01-01

    The aim of the present review is to discuss about the role of new probes for molecular imaging in the evaluation of prostate cancer (PCa). This review focuses particularly on the role of new promising radiotracers for the molecular imaging with PET/computed tomography in the detection of PCa recurrence. The role of these new imaging techniques to guide lesion-target therapies and the potential application of these molecular probes as theranostics agents is discussed. Finally, the molecular mechanisms underlying resistance to castration in PCa and the maintenance of active androgen receptor are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Cancer diagnostics: The journey from histomorphology to molecular profiling.

    Science.gov (United States)

    Ahmed, Atif A; Abedalthagafi, Malak

    2016-09-06

    Although histomorphology has made significant advances into the understanding of cancer etiology, classification and pathogenesis, it is sometimes complicated by morphologic ambiguities, and other shortcomings that necessitate the development of ancillary tests to complement its diagnostic value. A new approach to cancer patient management consists of targeting specific molecules or gene mutations in the cancer genome by inhibitory therapy. Molecular diagnostic tests and genomic profiling methods are increasingly being developed to identify tumor targeted molecular profile that is the basis of targeted therapy. Novel targeted therapy has revolutionized the treatment of gastrointestinal stromal tumor, renal cell carcinoma and other cancers that were previously difficult to treat with standard chemotherapy. In this review, we discuss the role of histomorphology in cancer diagnosis and management and the rising role of molecular profiling in targeted therapy. Molecular profiling in certain diagnostic and therapeutic difficulties may provide a practical and useful complement to histomorphology and opens new avenues for targeted therapy and alternative methods of cancer patient management.

  2. Epidemiological bases and molecular mechanisms linking obesity, diabetes, and cancer.

    Science.gov (United States)

    Gutiérrez-Salmerón, María; Chocarro-Calvo, Ana; García-Martínez, José Manuel; de la Vieja, Antonio; García-Jiménez, Custodia

    2017-02-01

    The association between diabetes and cancer was hypothesized almost one century ago. Today, a vast number of epidemiological studies support that obese and diabetic populations are more likely to experience tissue-specific cancers, but the underlying molecular mechanisms remain unknown. Obesity, diabetes, and cancer share many hormonal, immune, and metabolic changes that may account for the relationship between diabetes and cancer. In addition, antidiabetic treatments may have an impact on the occurrence and course of some cancers. Moreover, some anticancer treatments may induce diabetes. These observations aroused a great controversy because of the ethical implications and the associated commercial interests. We report an epidemiological update from a mechanistic perspective that suggests the existence of many common and differential individual mechanisms linking obesity and type 1 and 2 diabetes mellitus to certain cancers. The challenge today is to identify the molecular links responsible for this association. Classification of cancers by their molecular signatures may facilitate future mechanistic and epidemiological studies. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. Stress and its molecular consequences in cancer progression

    Directory of Open Access Journals (Sweden)

    Magdalena Surman

    2017-06-01

    Full Text Available Stress, caused by psychological, physiological and physical factors has an adverse impact on human body homeostasis. There are two kind of stress: short-term and chronic. Cancer patients usually live under chronic stress, caused by diagnosis-related strong emotional experience and depression, resulting from various difficulties associated with disease progression and treatment. At the molecular level, stress factors induce production and secretion of stress-related hormones, such as catecholamines, glucocorticoids and dopamine (as a part of adaptational body response, which influence both normal and transformed cells through their specific receptors. The particular effects exerted by these molecules on cancer cells have been also observed in in vitro cultures and include changes in proliferation, apoptosis susceptibility and migration/invasion potential. As a result, it has been suggested that stress hormones may be responsible for progression of malignancy and thus accelerate the metastasis formation in cancer patients. However, the clinical data on correlation between stress and the patients survival, as well as the molecular analysis of stress hormone receptors expression and action in cancer cell, have not yet provided an unequivocal answer. For this reason, extensive studies, on molecular and clinical level are needed to fully determine stress impact on cancerprogression and on the effectiveness of anti-cancer treatment. Nowadays, it seems reasonable that the personalization of anti-cancer therapy should also focus on mental state of cancer patients, and provide them with psychological tools or techniques for stress management.

  4. Breast cancer lung metastasis: Molecular biology and therapeutic implications.

    Science.gov (United States)

    Jin, Liting; Han, Bingchen; Siegel, Emily; Cui, Yukun; Giuliano, Armando; Cui, Xiaojiang

    2018-03-26

    Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis. Luminal breast tumors tend to metastasize to bone while basal-like breast cancer (BLBC) displays a lung tropism of metastasis. However, the mechanisms underlying this organ-specific pattern of metastasis still remain to be elucidated. In this review, we will summarize the recent advances regarding the molecular signaling pathways as well as the therapeutic strategies for treating breast cancer lung metastasis.

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

    Science.gov (United States)

    Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

    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. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

  6. Molecular mechanisms of cisplatin resistance in cervical cancer

    Directory of Open Access Journals (Sweden)

    Zhu H

    2016-06-01

    Full Text Available Haiyan Zhu, Hui Luo, Wenwen Zhang, Zhaojun Shen, Xiaoli Hu, Xueqiong Zhu Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. Keywords: cisplatin, epithelial–mesenchymal transition, microRNA, molecular mechanism, resistance

  7. [Epidemiology, risk factors and molecular pathogenesis of primary liver cancer].

    Science.gov (United States)

    Hagymási, Krisztina; Tulassay, Zsolt

    2008-03-23

    Primary liver cancer is the fifth most common cancer worldwide. Hepatocellular carcinoma accounts for 85-90% of primary liver cancers. Distribution of hepatocellular carcinoma shows variations among geographic regions and ethnic groups. Males have higher liver cancer rates than females. Hepatocellular carcinoma occurs within an established background of chronic liver disease and cirrhosis (70-90%). Major causes (80%) of hepatocellular carcinoma are hepatitis B, C virus infection, and aflatoxin exposition. Its development is a multistep process. We have a growing understanding on the molecular pathogenesis. Genetic and epigenetic changes activate oncogenes, inhibit tumorsuppressor genes, which result in autonomous cell proliferation. The chromosomal instability caused by telomere dysfunction, the growth-retrained environment and the alterations of the micro- and macroenvironment help the expansion of the malignant cells. Understanding the molecular mechanisms could improve the screening of patients with chronic liver disease, or cirrhosis, and the prevention as well as treatment of hepatocellular carcinoma.

  8. Pathogenesis of Gastric Cancer: Genetics and Molecular Classification.

    Science.gov (United States)

    Figueiredo, Ceu; Camargo, M C; Leite, Marina; Fuentes-Pananá, Ezequiel M; Rabkin, Charles S; Machado, José C

    Gastric cancer is the fifth most incident and the third most common cause of cancer-related death in the world. Infection with Helicobacter pylori is the major risk factor for this disease. Gastric cancer is the final outcome of a cascade of events that takes decades to occur and results from the accumulation of multiple genetic and epigenetic alterations. These changes are crucial for tumor cells to expedite and sustain the array of pathways involved in the cancer development, such as cell cycle, DNA repair, metabolism, cell-to-cell and cell-to-matrix interactions, apoptosis, angiogenesis, and immune surveillance. Comprehensive molecular analyses of gastric cancer have disclosed the complex heterogeneity of this disease. In particular, these analyses have confirmed that Epstein-Barr virus (EBV)-positive gastric cancer is a distinct entity. The identification of gastric cancer subtypes characterized by recognizable molecular profiles may pave the way for a more personalized clinical management and to the identification of novel therapeutic targets and biomarkers for screening, prognosis, prediction of response to treatment, and monitoring of gastric cancer progression.

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

    Science.gov (United States)

    Saletta, Federica; Wadham, Carol; Ziegler, David S; Marshall, Glenn M; Haber, Michelle; McCowage, Geoffrey; Norris, Murray D; Byrne, Jennifer A

    2014-06-01

    Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies. This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type. There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies. 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.

  10. Uncovering the molecular secrets of inflammatory breast cancer biology: an integrated analysis of three distinct affymetrix gene expression datasets.

    Science.gov (United States)

    Van Laere, Steven J; Ueno, Naoto T; Finetti, Pascal; Vermeulen, Peter; Lucci, Anthony; Robertson, Fredika M; Marsan, Melike; Iwamoto, Takayuki; Krishnamurthy, Savitri; Masuda, Hiroko; van Dam, Peter; Woodward, Wendy A; Viens, Patrice; Cristofanilli, Massimo; Birnbaum, Daniel; Dirix, Luc; Reuben, James M; Bertucci, François

    2013-09-01

    Inflammatory breast cancer (IBC) is a poorly characterized form of breast cancer. So far, the results of expression profiling in IBC are inconclusive due to various reasons including limited sample size. Here, we present the integration of three Affymetrix expression datasets collected through the World IBC Consortium allowing us to interrogate the molecular profile of IBC using the largest series of IBC samples ever reported. Affymetrix profiles (HGU133-series) from 137 patients with IBC and 252 patients with non-IBC (nIBC) were analyzed using unsupervised and supervised techniques. Samples were classified according to the molecular subtypes using the PAM50-algorithm. Regression models were used to delineate IBC-specific and molecular subtype-independent changes in gene expression, pathway, and transcription factor activation. Four robust IBC-sample clusters were identified, associated with the different molecular subtypes (Pmolecular subtype-independent 79-gene signature, which held independent prognostic value in a series of 871 nIBCs. Functional analysis revealed attenuated TGF-β signaling in IBC. We show that IBC is transcriptionally heterogeneous and that all molecular subtypes described in nIBC are detectable in IBC, albeit with a different frequency. The molecular profile of IBC, bearing molecular traits of aggressive breast tumor biology, shows attenuation of TGF-β signaling, potentially explaining the metastatic potential of IBC tumor cells in an unexpected manner. ©2013 AACR.

  11. Molecular Imaging and Precision Medicine in Breast Cancer.

    Science.gov (United States)

    Chudgar, Amy V; Mankoff, David A

    2017-01-01

    Precision medicine, basing treatment approaches on patient traits and specific molecular features of disease processes, has an important role in the management of patients with breast cancer as targeted therapies continue to improve. PET imaging offers noninvasive information that is complementary to traditional tissue biomarkers, including information about tumor burden, tumor metabolism, receptor status, and proliferation. Several PET agents that image breast cancer receptors can visually demonstrate the extent and heterogeneity of receptor-positive disease and help predict which tumors are likely to respond to targeted treatments. This review presents applications of PET imaging in the targeted treatment of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Endometrial cancer : from a molecular genetic perspective

    NARCIS (Netherlands)

    E. Smid-Koopman (Ellen)

    2002-01-01

    textabstractThe first observations indicative of a role of genetic factors in carcinogenesis were made as early as 1912, when Rous demonstrated that a filterable agent (i.e. virus) could induce cancer in chicken (Rous 1965). In 1914, Boveri postulated a "genetic" theory on carcinogenesis by

  13. 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...

  14. Barrett's esophagus: cancer and molecular biology

    NARCIS (Netherlands)

    Gibson, Michael K.; Dhaliwal, Arashinder S.; Clemons, Nicholas J.; Phillips, Wayne A.; Dvorak, Katerina; Tong, Daniel; Law, Simon; Pirchi, E. Daniel; Räsänen, Jari; Krasna, Mark J.; Parikh, Kaushal; Krishnadath, Kausilia K.; Chen, Yu; Griffiths, Leonard; Colleypriest, Benjamin J.; Farrant, J. Mark; Tosh, David; Das, Kiron M.; Bajpai, Manisha

    2013-01-01

    The following paper on the molecular biology of Barrett's esophagus (BE) includes commentaries on signaling pathways central to the development of BE including Hh, NF-κB, and IL-6/STAT3; surgical approaches for esophagectomy and classification of lesions by appropriate therapy; the debate over the

  15. Patients with Acromegaly Presenting with Colon Cancer: A Case Series

    Directory of Open Access Journals (Sweden)

    Murray B. Gordon

    2016-01-01

    Full Text Available Introduction. Frequent colonoscopy screenings are critical for early diagnosis of colon cancer in patients with acromegaly. Case Presentations. We performed a retrospective analysis of the incidental diagnoses of colon cancer from the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734. Colon cancer was identified in 2 patients (4.5%. Case  1 patient was a 36-year-old male with acromegaly who underwent transsphenoidal surgery to remove the pituitary adenoma. After surgery, the patient underwent routine colonoscopy screening, which revealed a 40 mm tubular adenoma in the descending colon. A T1N1a carcinoma was surgically removed, and 1 of 22 lymph nodes was positive for metastatic disease, leading to a diagnosis of stage 3 colon cancer. Case  2 patient was a 50-year-old male with acromegaly who underwent transsphenoidal surgery to remove a 2 cm pituitary adenoma. The patient reported severe cramping and lower abdominal pain, and an invasive 8.1 cm3 grade 2 adenocarcinoma with signet rings was identified in the ascending colon and removed. Of the 37 lymph nodes, 34 were positive for the presence of tumor cells, and stage 3c colon cancer was confirmed. Conclusion. Current guidelines for colonoscopy screening at the time of diagnosis of acromegaly and at appropriate follow-up intervals should be followed.

  16. Pomegranate Extracts and Cancer Prevention: Molecular and Cellular Activities

    Science.gov (United States)

    Syed, Deeba N.; Chamcheu, Jean-Christopher; Adhami, Vaqar M.; Mukhtar, Hasan

    2014-01-01

    There is increased appreciation by the scientific community that dietary phytochemicals can be potential weapons in the fight against cancer. Emerging data has provided new insights into the molecular and cellular framework needed to establish novel mechanism-based strategies for cancer prevention by selective bioactive food components. The unique chemical composition of the pomegranate fruit, rich in antioxidant tannins and flavonoids has drawn the attention of many investigators. Polyphenol rich fractions derived from the pomegranate fruit have been studied for their potential chemopreventive and/or cancer therapeutic effects in several animal models. Although data from in vitro and in vivo studies look convincing, well designed clinical trials in humans are needed to ascertain whether pomegranate can become part of our armamentarium against cancer. This review summarizes the available literature on the effects of pomegranate against various cancers. PMID:23094914

  17. Evaluation of the pathological response and prognosis following neoadjuvant chemotherapy in molecular subtypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-06-01

    Full Text Available Yue Zhao,1 Xiaoqiu Dong,2 Rongguo Li,1 Xiao Ma,1 Jian Song,1 Yingjie Li,3 Dongwei Zhang1 1Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, 2Department of Ultrasonography, Fourth Affiliated Hospital of Harbin Medical University, 3Department of Pathology, Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China Background: The pathological complete response of neoadjuvant chemotherapy for breast cancer correlates with the prognosis for survival. Tumors may have different prognoses according to their molecular subtypes. This study was performed to evaluate the relevance of the pathological response and prognosis following neoadjuvant chemotherapy in the molecular subtypes of breast cancer.Methods: A consecutive series of 88 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Patients were classified into four molecular subtypes based on the immunohistochemistry profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. The histological response was assessed according to Miller-Payne grading (MPG and Residual Disease in Breast and Nodes (RDBN.Results: Ten patients (11.4% achieved a pathological complete response, assessed according to RDBN. The pathological complete response rate was 13.6% according to MPG. Patients with the triple-negative subtype were more likely to achieve a pathological complete response than those with luminal A breast cancer (P=0.03. MPG and RDBN are independent predictors of distant disease-free survival and local recurrence-free survival, but do not predict overall survival. Ki-67, size of invasive carcinoma, lymph nodes, molecular subtypes, MPG, and RDBN are important predictors of distant disease-free survival, local recurrence-free survival, and overall survival.Conclusion: MPG and RDBN were similarly related to the patient’s prognosis. MPG was more suitable for evaluation of distant disease

  18. Synthesis, anticancer activity and molecular docking studies on a series of heterocyclic trans-cyanocombretastatin analogues as antitubulin agents.

    Science.gov (United States)

    Penthala, Narsimha Reddy; Zong, Hongliang; Ketkar, Amit; Madadi, Nikhil Reddy; Janganati, Venumadav; Eoff, Robert L; Guzman, Monica L; Crooks, Peter A

    2015-03-06

    A series of heterocyclic combretastatin analogues have been synthesized and evaluated for their anticancer activity against a panel of 60 human cancer cell lines. The most potent compounds were two 3,4,5-trimethoxy phenyl analogues containing either an (Z)-indol-2-yl (8) or (Z)-benzo[b]furan-2-yl (12) moiety; these compounds exhibited GI50 values of Compounds 8, and 12 and two previously reported compounds in the same structural class, i.e. 29 and 31, also showed potent anti-leukemic activity against leukemia MV4-11 cell lines with LD50 values = 44 nM, 47 nM, 18 nM, and 180 nM, respectively. From the NCI anti-cancer screening results and the data from the in vitro toxicity screening on cultured AML cells, seven compounds: 8, 12, 21, 23, 25, 29 and 31 were screened for their in vitro inhibitory activity on tubulin polymerization in MV4-11 AML cells; at 50 nM, 8 and 29 inhibited polymerization of tubulin by >50%. The binding modes of the three most active compounds (8, 12 and 29) to tubulin were also investigated utilizing molecular docking studies. All three molecules were observed to bind in the same hydrophobic pocket at the interface of α- and β-tubulin that is occupied by colchicine, and were stabilized by van der Waals' interactions with surrounding tubulin residues. The results from the tubulin polymerization and molecular docking studies indicate that compounds 8 and 29 are the most potent anti-leukemic compounds in this structural class, and are considered lead compounds for further development as anti-leukemic drugs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

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

    Science.gov (United States)

    Omer, Ankur; Singh, Poonam

    2017-05-01

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

  20. Validation of a radiosensitivity molecular signature in breast cancer

    NARCIS (Netherlands)

    S.A. Eschrich (Steven); C. Fulp (Carl); Y. Pawitan (Yudi); J.A. Foekens (John); M. Smid (Marcel); J.W.M. Martens (John); M. Echevarria (Michelle); P.S. Kamath (Patrick); J.-H. Lee (Ji-Hyun); E.E. Harris (Eleanor); J. Bergh (Jonas); J.F. Torres-Roca (Javier)

    2012-01-01

    textabstractPurpose: Previously, we developed a radiosensitivity molecular signature [radiosensitivity index (RSI)] that was clinically validated in 3 independent datasets (rectal, esophageal, and head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT)-treated breast cancer patients.

  1. Guidance for laboratories performing molecular pathology for cancer patients

    NARCIS (Netherlands)

    Cree, Ian A.; Deans, Zandra; Ligtenberg, Marjolijn J. L.; Normanno, Nicola; Edsjo, Anders; Rouleau, Etienne; Sole, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J. Han

    2014-01-01

    Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this

  2. Guidance for laboratories performing molecular pathology for cancer patients

    NARCIS (Netherlands)

    Cree, Ian A.; Deans, Zandra; Ligtenberg, Marjolijn J. L.; Normanno, Nicola; Edsjo, Anders; Rouleau, Etienne; Sole, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J. Han

    Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this

  3. [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. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  4. Molecular buckets: cyclodextrins for oral cancer therapy

    OpenAIRE

    Calleja, P. (Patricia); Huarte, J. (Judit); Agüeros, M. (Maite); Ruiz-Gaton, L. (Luisa); Espuelas, S. (Socorro); Irache, J.M. (Juan Manuel)

    2012-01-01

    The oral route is preferred by patients for drug administration due to its convenience, resulting in improved compliance. Unfortunately, for a number of drugs (e.g., anticancer drugs), this route of administration remains a challenge. Oral chemotherapy may be an attractive option and especially appropriate for chronic treatment of cancer. However, this route of administration is particularly complicated for the administration of anticancer drugs ascribed to Class IV of the Biopharmaceutical C...

  5. 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.

  6. [Prognostic and predictive molecular markers for urologic cancers].

    Science.gov (United States)

    Hartmann, A; Schlomm, T; Bertz, S; Heinzelmann, J; Hölters, S; Simon, R; Stoehr, R; Junker, K

    2014-04-01

    Molecular prognostic factors and genetic alterations as predictive markers for cancer-specific targeted therapies are used today in the clinic for many malignancies. In recent years, many molecular markers for urogenital cancers have also been identified. However, these markers are not clinically used yet. In prostate cancer, novel next-generation sequencing methods revealed a detailed picture of the molecular changes. There is growing evidence that a combination of classical histopathological and validated molecular markers could lead to a more precise estimation of prognosis, thus, resulting in an increasing number of patients with active surveillance as a possible treatment option. In patients with urothelial carcinoma, histopathological factors but also the proliferation of the tumor, mutations in oncogenes leading to an increasing proliferation rate and changes in genes responsible for invasion and metastasis are important. In addition, gene expression profiles which could distinguish aggressive tumors with high risk of metastasis from nonmetastasizing tumors have been recently identified. In the future, this could potentially allow better selection of patients needing systemic perioperative treatment. In renal cell carcinoma, many molecular markers that are associated with metastasis and survival have been identified. Some of these markers were also validated as independent prognostic markers. Selection of patients with primarily organ-confined tumors and increased risk of metastasis for adjuvant systemic therapy could be clinically relevant in the future.

  7. 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.

  8. Cancer Prevention Programs in the Workplace. WBGH Worksite Wellness Series.

    Science.gov (United States)

    Eriksen, Michael P.

    When employees develop cancer, businesses bear not only the direct medical costs of the disease, but also the indirect costs associated with lost work time, disability payments, loss of a trained employee, and retraining. Research has confirmed that aggressive prevention and screening programs can be, and indeed are, effective in limiting the…

  9. A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers

    NARCIS (Netherlands)

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

    2018-01-01

    We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations

  10. Genetic Alterations in the Molecular Subtypes of Bladder Cancer: Illustration in the Cancer Genome Atlas Dataset.

    Science.gov (United States)

    Choi, Woonyoung; Ochoa, Andrea; McConkey, David J; Aine, Mattias; Höglund, Mattias; Kim, William Y; Real, Francisco X; Kiltie, Anne E; Milsom, Ian; Dyrskjøt, Lars; Lerner, Seth P

    2017-09-01

    Recent whole genome mRNA expression profiling studies revealed that bladder cancers can be grouped into molecular subtypes, some of which share clinical properties and gene expression patterns with the intrinsic subtypes of breast cancer and the molecular subtypes found in other solid tumors. The molecular subtypes in other solid tumors are enriched with specific mutations and copy number aberrations that are thought to underlie their distinct progression patterns, and biological and clinical properties. The availability of comprehensive genomic data from The Cancer Genome Atlas (TCGA) and other large projects made it possible to correlate the presence of DNA alterations with tumor molecular subtype membership. Our overall goal was to determine whether specific DNA mutations and/or copy number variations are enriched in specific molecular subtypes. We used the complete TCGA RNA-seq dataset and three different published classifiers developed by our groups to assign TCGA's bladder cancers to molecular subtypes, and examined the prevalence of the most common DNA alterations within them. We interpreted the results against the background of what was known from the published literature about the prevalence of these alterations in nonmuscle-invasive and muscle-invasive bladder cancers. The results confirmed that alterations involving RB1 and NFE2L2 were enriched in basal cancers, whereas alterations involving FGFR3 and KDM6A were enriched in luminal tumors. The results further reinforce the conclusion that the molecular subtypes of bladder cancer are distinct disease entities with specific genetic alterations. Our observation showed that some of subtype-enriched mutations and copy number aberrations are clinically actionable, which has direct implications for the clinical management of patients with bladder cancer. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  11. Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers.

    Science.gov (United States)

    Wu, Hua-Hsi; Lin, Wen-chang; Tsai, Kuo-Wang

    2014-01-23

    Carcinoma of the stomach is one of the most prevalent cancer types in the world. Although the incidence of gastric cancer is declining, the outcomes of gastric cancer patients remain dismal because of the lack of effective biomarkers to detect early gastric cancer. Modern biomedical research has explored many potential gastric cancer biomarker genes by utilising serum protein antigens, oncogenic genes or gene families through improving molecular biological technologies, such as microarray, RNA-Seq and the like. Recently, the small noncoding microRNAs (miRNAs) have been suggested to be critical regulators in the oncogenesis pathways and to serve as useful clinical biomarkers. This new class of biomarkers is emerging as a novel molecule for cancer diagnosis and prognosis, including gastric cancer. By translational suppression of target genes, miRNAs play a significant role in the gastric cancer cell physiology and tumour progression. There are potential implications of previously discovered gastric cancer molecular biomarkers and their expression modulations by respective miRNAs. Therefore, many miRNAs are found to play oncogenic roles or tumour-suppressing functions in human cancers. With the surprising stability of miRNAs in tissues, serum or other body fluids, miRNAs have emerged as a new type of cancer biomarker with immeasurable clinical potential.

  12. Molecular portrait of breast cancer in China reveals comprehensive transcriptomic likeness to Caucasian breast cancer and low prevalence of luminal A subtype

    International Nuclear Information System (INIS)

    Huang, Xiaoyan; Dugo, Matteo; Callari, Maurizio; Sandri, Marco; De Cecco, Loris; Valeri, Barbara; Carcangiu, Maria Luisa; Xue, Jingyan; Bi, Rui; Veneroni, Silvia; Daidone, Maria Grazia; Ménard, Sylvie; Tagliabue, Elda; Shao, Zhimin; Wu, Jiong; Orlandi, Rosaria

    2015-01-01

    The recent dramatic increase in breast cancer incidence across China with progressive urbanization and economic development has signaled the urgent need for molecular and clinical detailing of breast cancer in the Chinese population. Our analyses of a unique transethnic collection of breast cancer frozen specimens from Shanghai Fudan Cancer Center (Chinese Han) profiled simultaneously with an analogous Caucasian Italian series revealed consistent transcriptomic data lacking in batch effects. The prevalence of Luminal A subtype was significantly lower in Chinese series, impacting the overall prevalence of estrogen receptor (ER)-positive disease in a large cohort of Chinese/Caucasian patients. Unsupervised and supervised comparison of gene and microRNA (miRNA) profiles of Chinese and Caucasian samples revealed extensive similarity in the comprehensive taxonomy of transcriptional elements regulating breast cancer biology. Partition of gene expression data using gene lists relevant to breast cancer as “intrinsic” and “extracellular matrix” genes identified Chinese and Caucasian subgroups with equivalent global gene and miRNA profiles. These findings indicate that in the Chinese and Caucasian groups, breast neoplasia and the surrounding stromal characteristics undergo the same differentiation and molecular processes. Transcriptional similarity across transethnic cohorts may simplify translational medicine approaches and clinical management of breast cancer patients worldwide

  13. Barrett's esophagus: cancer and molecular biology.

    Science.gov (United States)

    Gibson, Michael K; Dhaliwal, Arashinder S; Clemons, Nicholas J; Phillips, Wayne A; Dvorak, Katerina; Tong, Daniel; Law, Simon; Pirchi, E Daniel; Räsänen, Jari; Krasna, Mark J; Parikh, Kaushal; Krishnadath, Kausilia K; Chen, Yu; Griffiths, Leonard; Colleypriest, Benjamin J; Farrant, J Mark; Tosh, David; Das, Kiron M; Bajpai, Manisha

    2013-10-01

    The following paper on the molecular biology of Barrett's esophagus (BE) includes commentaries on signaling pathways central to the development of BE including Hh, NF-κB, and IL-6/STAT3; surgical approaches for esophagectomy and classification of lesions by appropriate therapy; the debate over the merits of minimally invasive esophagectomy versus open surgery; outcomes for patients with pharyngolaryngoesophagectomy; the applications of neoadjuvant chemotherapy and chemoradiotherapy; animal models examining the surgical models of BE and esophageal adenocarcinoma; the roles of various morphogens and Cdx2 in BE; and the use of in vitro BE models for chemoprevention studies. © 2013 New York Academy of Sciences.

  14. Genomic analysis and selected molecular pathways in rare cancers

    International Nuclear Information System (INIS)

    Liu, Stephen V; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Demeure, Michael J; Ramanathan, Ramesh K; Von Hoff, Daniel D; Barrett, Michael T; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Eng, Cathy

    2012-01-01

    It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer. (paper)

  15. Biomarker assessment and molecular testing for prognostication in breast cancer.

    Science.gov (United States)

    Kos, Zuzana; Dabbs, David J

    2016-01-01

    Current treatment of breast cancer incorporates clinical, pathological and molecular data. Oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) define prognosis and identify tumours for targeted therapy, and remain the sole established single-molecule biomarkers defining the minimum breast cancer pathology data set. Ki67 remains one of the most promising yet controversial biomarkers in breast cancer, implemented routinely in some, but not all, pathology departments. Beyond the single-molecule biomarkers, a host of multigene expression tests have been developed to interrogate the driver pathways and biology of individual breast cancers to predict clinical outcome more accurately. A minority of these assays have entered into clinical practice. This review focuses on the established biomarkers of ER, PR and HER2, the controversial but clinically implemented biomarker Ki67 and the currently marketed gene expression signatures. © 2015 John Wiley & Sons Ltd.

  16. Molecular Signaling Pathways Mediating Osteoclastogenesis Induced by Prostate Cancer Cells

    International Nuclear Information System (INIS)

    Rafiei, Shahrzad; Komarova, Svetlana V

    2013-01-01

    Advanced prostate cancer commonly metastasizes to bone leading to osteoblastic and osteolytic lesions. Although an osteolytic component governed by activation of bone resorbing osteoclasts is prominent in prostate cancer metastasis, the molecular mechanisms of prostate cancer-induced osteoclastogenesis are not well-understood. We studied the effect of soluble mediators released from human prostate carcinoma cells on osteoclast formation from mouse bone marrow and RAW 264.7 monocytes. Soluble factors released from human prostate carcinoma cells significantly increased viability of naïve bone marrow monocytes, as well as osteoclastogenesis from precursors primed with receptor activator of nuclear factor κ-B ligand (RANKL). The prostate cancer-induced osteoclastogenesis was not mediated by RANKL as it was not inhibited by osteoprotegerin (OPG). However inhibition of TGFβ receptor I (TβRI), or macrophage-colony stimulating factor (MCSF) resulted in attenuation of prostate cancer-induced osteoclastogenesis. We characterized the signaling pathways induced in osteoclast precursors by soluble mediators released from human prostate carcinoma cells. Prostate cancer factors increased basal calcium levels and calcium fluctuations, induced nuclear localization of nuclear factor of activated t-cells (NFAT)c1, and activated prolonged phosphorylation of ERK1/2 in RANKL-primed osteoclast precursors. Inhibition of calcium signaling, NFATc1 activation, and ERK1/2 phosphorylation significantly reduced the ability of prostate cancer mediators to stimulate osteoclastogenesis. This study reveals the molecular mechanisms underlying the direct osteoclastogenic effect of prostate cancer derived factors, which may be beneficial in developing novel osteoclast-targeting therapeutic approaches

  17. The implications of breast cancer molecular phenotype for radiation oncology

    Directory of Open Access Journals (Sweden)

    Shirin eSioshansi

    2011-06-01

    Full Text Available The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence in the hormone receptor positive luminal subtypes compared to hormone receptor negative subtypes (triple negative and HER2-enriched. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of local recurrence. Unfortunately, no such remedy exists to address the increased risk of local recurrence for patients with triple negative tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and local recurrence following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased local recurrence in triple negative breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation and the appropriateness of accelerated partial breast irradiation.

  18. The Implications of Breast Cancer Molecular Phenotype for Radiation Oncology

    Energy Technology Data Exchange (ETDEWEB)

    Sioshansi, Shirin [Department of Radiation Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA (United States); Department of Radiation Oncology, Rhode Island Hospital, Warren Alpert School of Medicine at Brown University, Providence, RI (United States); Huber, Kathryn E. [Department of Radiation Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA (United States); Wazer, David E., E-mail: dwazer@tuftsmedicalcenter.org [Department of Radiation Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA (United States); Department of Radiation Oncology, Rhode Island Hospital, Warren Alpert School of Medicine at Brown University, Providence, RI (United States)

    2011-06-28

    The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence, and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence (LR) in the hormone receptor (HR) positive luminal subtypes compared to HR negative subtypes [triple negative (TN) and HER2-enriched]. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of LR. Unfortunately, no such remedy exists to address the increased risk of LR for patients with TN tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and LR following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased LR in TN breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation, and the appropriateness of accelerated partial breast irradiation.

  19. The Implications of Breast Cancer Molecular Phenotype for Radiation Oncology

    International Nuclear Information System (INIS)

    Sioshansi, Shirin; Huber, Kathryn E.; Wazer, David E.

    2011-01-01

    The identification of distinct molecular subtypes of breast cancer has advanced the understanding and treatment of breast cancer by providing insight into prognosis, patterns of recurrence, and effectiveness of therapy. The prognostic significance of molecular phenotype with regard to distant recurrences and overall survival are well established in the literature and has been readily incorporated into systemic therapy management decisions. However, despite the accumulating data suggesting similar prognostic significance for locoregional recurrence, integration of molecular phenotype into local management decision making has lagged. Although there are some conflicting reports, collectively the literature supports a low risk of local recurrence (LR) in the hormone receptor (HR) positive luminal subtypes compared to HR negative subtypes [triple negative (TN) and HER2-enriched]. The development of targeted therapies, such as trastuzumab for the treatment of HER2-enriched subtype, has been shown to mitigate the increased risk of LR. Unfortunately, no such remedy exists to address the increased risk of LR for patients with TN tumors, making it a clinical challenge for radiation oncologists. In this review we discuss the correlation between molecular subtype and LR following either breast conservation therapy or mastectomy. We also explore the possible mechanisms for increased LR in TN breast cancer and radiotherapeutic implications for this population, such as the safety of breast conservation, consideration of dose escalation, and the appropriateness of accelerated partial breast irradiation.

  20. 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

    2011-05-01

    Gastric cancer may be subdivided into 3 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. Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (National Cancer Institute, NCI #5917) underwent endoscopic biopsy for fresh tumor procurement. Four to 6 targeted biopsies of the primary tumor were obtained. Macrodissection was carried out to ensure more than 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. 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 3 gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross-validation error was 0.14, suggesting that more than 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. Subtypes of gastric cancer that have epidemiologic and histologic distinctions 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. ©2011 AACR.

  1. 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. 2010 Elsevier Ltd. All rights reserved.

  2. Breast cancer molecular subtype classification using deep features: preliminary results

    Science.gov (United States)

    Zhu, Zhe; Albadawy, Ehab; Saha, Ashirbani; Zhang, Jun; Harowicz, Michael R.; Mazurowski, Maciej A.

    2018-02-01

    Radiogenomics is a field of investigation that attempts to examine the relationship between imaging characteris- tics of cancerous lesions and their genomic composition. This could offer a noninvasive alternative to establishing genomic characteristics of tumors and aid cancer treatment planning. While deep learning has shown its supe- riority in many detection and classification tasks, breast cancer radiogenomic data suffers from a very limited number of training examples, which renders the training of the neural network for this problem directly and with no pretraining a very difficult task. In this study, we investigated an alternative deep learning approach referred to as deep features or off-the-shelf network approach to classify breast cancer molecular subtypes using breast dynamic contrast enhanced MRIs. We used the feature maps of different convolution layers and fully connected layers as features and trained support vector machines using these features for prediction. For the feature maps that have multiple layers, max-pooling was performed along each channel. We focused on distinguishing the Luminal A subtype from other subtypes. To evaluate the models, 10 fold cross-validation was performed and the final AUC was obtained by averaging the performance of all the folds. The highest average AUC obtained was 0.64 (0.95 CI: 0.57-0.71), using the feature maps of the last fully connected layer. This indicates the promise of using this approach to predict the breast cancer molecular subtypes. Since the best performance appears in the last fully connected layer, it also implies that breast cancer molecular subtypes may relate to high level image features

  3. Diagnosis and management of differentiated thyroid cancer using molecular biology.

    Science.gov (United States)

    Witt, Robert L; Ferris, Robert L; Pribitkin, Edmund A; Sherman, Steven I; Steward, David L; Nikiforov, Yuri E

    2013-04-01

    To define molecular biology in clinical practice for diagnosis, surgical management, and prognostication of differentiated thyroid cancer. Ovid Medline 2006-2012 Manuscripts with clinical correlates. Papillary thyroid carcinomas harbor point mutations of the BRAF and RAS genes or RET/PTC rearrangements, all of which activate the mitogen-activated protein kinase pathway. These mutually exclusive mutations are found in 70% of PTC. BRAF mutation is found in 45% of papillary thyroid cancer and is highly specific. Follicular carcinomas are known to harbor RAS mutation or PAX8/PPARγ rearrangement. These mutations are also mutually exclusive and identified in 70% of follicular carcinomas. Molecular classifiers measure the expression of a large number of genes on a microarray chip providing a substantial negative predictive value pending further validation. 1) 20% to 30% of cytologically classified Follicular Neoplasms and Follicular Lesion of Undetermined Significance collectively are malignant on final pathology. Approximately 70% to 80% of thyroid lobectomies performed solely for diagnostic purposes are benign. Molecular alteration testing may reduce the number of unnecessary thyroid procedures, 2) may reduce the number of completion thyroidectomies, and 3) may lead to more individualized operative and postoperative management. Molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ for follicular lesion of undetermined significance and follicular neoplasm improve specificity, whereas molecular classifiers may add negative predictive value to fine needle aspiration diagnosis. Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.

  4. Snus (nass and oral cancer: A case series report

    Directory of Open Access Journals (Sweden)

    Maryam Alsadat Hashemipour

    2013-01-01

    Full Text Available Snus (nass is a form of snuff used in a similar manner to American dipping tobacco, but it does not typically result in a need for spitting. Possible hazards associated with this material include malignant and premalignant lesions in the oral cavity and gastrointestinal tract. The use of smokeless tobacco has increased in the Middle East in recent decades, particularly among teenagers and young adults. Therefore, practitioners must be able to recognize malignant and premalignant lesions. Although, an estimated 10-25% of the world′s population uses smokeless tobacco, this practice is virtually unknown in Iran. The aim of this study is to report a series of cases of squamous cell carcinoma and verrucous carcinoma occurring in the users of snus, who referred to the Department of Oral Medicine in Kerman Dental School.

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

    International Nuclear Information System (INIS)

    Vermeulen, Jeroen F; Brussel, Aram SA van; Groep, Petra van der; Morsink, Folkert HM; Bult, Peter; Wall, Elsken van der; Diest, Paul J van

    2012-01-01

    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. 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. 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. 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

  6. 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.

  7. Two dimensional molecular electronics spectroscopy for molecular fingerprinting, DNA sequencing, and cancerous DNA recognition.

    Science.gov (United States)

    Rajan, Arunkumar Chitteth; Rezapour, Mohammad Reza; Yun, Jeonghun; Cho, Yeonchoo; Cho, Woo Jong; Min, Seung Kyu; Lee, Geunsik; Kim, Kwang S

    2014-02-25

    Laser-driven molecular spectroscopy of low spatial resolution is widely used, while electronic current-driven molecular spectroscopy of atomic scale resolution has been limited because currents provide only minimal information. However, electron transmission of a graphene nanoribbon on which a molecule is adsorbed shows molecular fingerprints of Fano resonances, i.e., characteristic features of frontier orbitals and conformations of physisorbed molecules. Utilizing these resonance profiles, here we demonstrate two-dimensional molecular electronics spectroscopy (2D MES). The differential conductance with respect to bias and gate voltages not only distinguishes different types of nucleobases for DNA sequencing but also recognizes methylated nucleobases which could be related to cancerous cell growth. This 2D MES could open an exciting field to recognize single molecule signatures at atomic resolution. The advantages of the 2D MES over the one-dimensional (1D) current analysis can be comparable to those of 2D NMR over 1D NMR analysis.

  8. Deep Sequencing of Urinary RNAs for Bladder Cancer Molecular Diagnostics.

    Science.gov (United States)

    Sin, Mandy L Y; Mach, Kathleen E; Sinha, Rahul; Wu, Fan; Trivedi, Dharati R; Altobelli, Emanuela; Jensen, Kristin C; Sahoo, Debashis; Lu, Ying; Liao, Joseph C

    2017-07-15

    Purpose: The majority of bladder cancer patients present with localized disease and are managed by transurethral resection. However, the high rate of recurrence necessitates lifetime cystoscopic surveillance. Developing a sensitive and specific urine-based test would significantly improve bladder cancer screening, detection, and surveillance. Experimental Design: RNA-seq was used for biomarker discovery to directly assess the gene expression profile of exfoliated urothelial cells in urine derived from bladder cancer patients ( n = 13) and controls ( n = 10). Eight bladder cancer specific and 3 reference genes identified by RNA-seq were quantitated by qPCR in a training cohort of 102 urine samples. A diagnostic model based on the training cohort was constructed using multiple logistic regression. The model was further validated in an independent cohort of 101 urines. Results: A total of 418 genes were found to be differentially expressed between bladder cancer and controls. Validation of a subset of these genes was used to construct an equation for computing a probability of bladder cancer score (P BC ) based on expression of three markers ( ROBO1, WNT5A , and CDC42BPB ). Setting P BC = 0.45 as the cutoff for a positive test, urine testing using the three-marker panel had overall 88% sensitivity and 92% specificity in the training cohort. The accuracy of the three-marker panel in the independent validation cohort yielded an AUC of 0.87 and overall 83% sensitivity and 89% specificity. Conclusions: Urine-based molecular diagnostics using this three-marker signature could provide a valuable adjunct to cystoscopy and may lead to a reduction of unnecessary procedures for bladder cancer diagnosis. Clin Cancer Res; 23(14); 3700-10. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

    Science.gov (United States)

    2011-07-01

    quantitatively and dynamically detect molecular markers of breast cancer in vivo without tissue removal or directly after removal in a surgical...hour oshells by c es, the nano ting to a fin ER2- positiv (CHTN) th tinction spect ter of 276 nm sert depicts co microscopy. n was visua rption...conclusively determine the penetration depth of the nanoshells. Additionally, a quantitative difference of the nanoshell signal at the surface of the Her2

  10. Time-Series Analyses of Transcriptomes and Proteomes Reveal Molecular Networks Underlying Oil Accumulation in Canola.

    Science.gov (United States)

    Wan, Huafang; Cui, Yixin; Ding, Yijuan; Mei, Jiaqin; Dong, Hongli; Zhang, Wenxin; Wu, Shiqi; Liang, Ying; Zhang, Chunyu; Li, Jiana; Xiong, Qing; Qian, Wei

    2016-01-01

    Understanding the regulation of lipid metabolism is vital for genetic engineering of canola ( Brassica napus L.) to increase oil yield or modify oil composition. We conducted time-series analyses of transcriptomes and proteomes to uncover the molecular networks associated with oil accumulation and dynamic changes in these networks in canola. The expression levels of genes and proteins were measured at 2, 4, 6, and 8 weeks after pollination (WAP). Our results show that the biosynthesis of fatty acids is a dominant cellular process from 2 to 6 WAP, while the degradation mainly happens after 6 WAP. We found that genes in almost every node of fatty acid synthesis pathway were significantly up-regulated during oil accumulation. Moreover, significant expression changes of two genes, acetyl-CoA carboxylase and acyl-ACP desaturase, were detected on both transcriptomic and proteomic levels. We confirmed the temporal expression patterns revealed by the transcriptomic analyses using quantitative real-time PCR experiments. The gene set association analysis show that the biosynthesis of fatty acids and unsaturated fatty acids are the most significant biological processes from 2-4 WAP and 4-6 WAP, respectively, which is consistent with the results of time-series analyses. These results not only provide insight into the mechanisms underlying lipid metabolism, but also reveal novel candidate genes that are worth further investigation for their values in the genetic engineering of canola.

  11. Molecular Subgroup of Primary Prostate Cancer Presenting with Metastatic Biology.

    Science.gov (United States)

    Walker, Steven M; Knight, Laura A; McCavigan, Andrena M; Logan, Gemma E; Berge, Viktor; Sherif, Amir; Pandha, Hardev; Warren, Anne Y; Davidson, Catherine; Uprichard, Adam; Blayney, Jaine K; Price, Bethanie; Jellema, Gera L; Steele, Christopher J; Svindland, Aud; McDade, Simon S; Eden, Christopher G; Foster, Chris; Mills, Ian G; Neal, David E; Mason, Malcolm D; Kay, Elaine W; Waugh, David J; Harkin, D Paul; Watson, R William; Clarke, Noel W; Kennedy, Richard D

    2017-10-01

    Approximately 4-25% of patients with early prostate cancer develop disease recurrence following radical prostatectomy. To identify a molecular subgroup of prostate cancers with metastatic potential at presentation resulting in a high risk of recurrence following radical prostatectomy. Unsupervised hierarchical clustering was performed using gene expression data from 70 primary resections, 31 metastatic lymph nodes, and 25 normal prostate samples. Independent assay validation was performed using 322 radical prostatectomy samples from four sites with a mean follow-up of 50.3 months. Molecular subgroups were identified using unsupervised hierarchical clustering. A partial least squares approach was used to generate a gene expression assay. Relationships with outcome (time to biochemical and metastatic recurrence) were analysed using multivariable Cox regression and log-rank analysis. A molecular subgroup of primary prostate cancer with biology similar to metastatic disease was identified. A 70-transcript signature (metastatic assay) was developed and independently validated in the radical prostatectomy samples. Metastatic assay positive patients had increased risk of biochemical recurrence (multivariable hazard ratio [HR] 1.62 [1.13-2.33]; p=0.0092) and metastatic recurrence (multivariable HR=3.20 [1.76-5.80]; p=0.0001). A combined model with Cancer of the Prostate Risk Assessment post surgical (CAPRA-S) identified patients at an increased risk of biochemical and metastatic recurrence superior to either model alone (HR=2.67 [1.90-3.75]; pmolecular subgroup of primary prostate cancers with metastatic potential. The metastatic assay may improve the ability to detect patients at risk of metastatic recurrence following radical prostatectomy. The impact of adjuvant therapies should be assessed in this higher-risk population. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  12. Molecular chess? Hallmarks of anti-cancer drug resistance.

    Science.gov (United States)

    Cree, Ian A; Charlton, Peter

    2017-01-05

    The development of resistance is a problem shared by both classical chemotherapy and targeted therapy. Patients may respond well at first, but relapse is inevitable for many cancer patients, despite many improvements in drugs and their use over the last 40 years. Resistance to anti-cancer drugs can be acquired by several mechanisms within neoplastic cells, defined as (1) alteration of drug targets, (2) expression of drug pumps, (3) expression of detoxification mechanisms, (4) reduced susceptibility to apoptosis, (5) increased ability to repair DNA damage, and (6) altered proliferation. It is clear, however, that changes in stroma and tumour microenvironment, and local immunity can also contribute to the development of resistance. Cancer cells can and do use several of these mechanisms at one time, and there is considerable heterogeneity between tumours, necessitating an individualised approach to cancer treatment. As tumours are heterogeneous, positive selection of a drug-resistant population could help drive resistance, although acquired resistance cannot simply be viewed as overgrowth of a resistant cancer cell population. The development of such resistance mechanisms can be predicted from pre-existing genomic and proteomic profiles, and there are increasingly sophisticated methods to measure and then tackle these mechanisms in patients. The oncologist is now required to be at least one step ahead of the cancer, a process that can be likened to 'molecular chess'. Thus, as well as an increasing role for predictive biomarkers to clinically stratify patients, it is becoming clear that personalised strategies are required to obtain best results.

  13. Cisplatin in cancer therapy: molecular mechanisms of action.

    Science.gov (United States)

    Dasari, Shaloam; Tchounwou, Paul Bernard

    2014-10-05

    Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum-containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum-based drugs, and discusses its uses (either alone or in combination with other drugs) for the treatment of various human cancers. A special attention is paid to its molecular mechanisms of action, and its undesirable side effects. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Cisplatin in cancer therapy: molecular mechanisms of action

    Science.gov (United States)

    Dasari, Shaloam; Tchounwou, Paul Bernard

    2014-01-01

    Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, because of drug resistance and numerous undesirable side effects such as severe kidney problems, allergic reactions, decrease immunity to infections, gastrointestinal disorders, hemorrhage, and hearing loss especially in younger patients, other platinum-containing anti-cancer drugs such as carboplatin, oxaliplatin and others, have also been used. Furthermore, combination therapies of cisplatin with other drugs have been highly considered to overcome drug-resistance and reduce toxicity. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum-based drugs, and discusses its uses (either alone or in combination with other drugs) for the treatment of various human cancers. A special attention is given to its molecular mechanisms of action, and its undesirable side effects. PMID:25058905

  15. Antitumor evaluation and 3D-QSAR studies of a new series of the spiropyrroloquinoline isoindolinone/aza-isoindolinone derivatives by comparative molecular field analysis (CoMFA).

    Science.gov (United States)

    Sadeghzadeh, Masoud; Salahinejad, Maryam; Zarezadeh, Nahid; Ghandi, Mehdi; Baghery, Maryam Keshavarz

    2017-11-01

    In current study, antitumor activity of two series of the newly synthesized spiropyrroloquinoline isoindolinone and spiropyrroloquinoline aza-isoindolinone scaffolds was evaluated against three human breast normal and cancer cell lines (MCF-10A, MCF-7 and SK-BR-3) and compared with cytotoxicity values of doxorubicin and colchicine as the standard drugs. It was found that several compounds were endowed with cytotoxicity in the low micromolar range. Among these two series, compounds 6i, 6j, 6k and 7l, 7m, 7n, 7o containing 3-ethyl-1H-indole moiety were found to be highly effective against both cancer cell lines ranging from [Formula: see text] to [Formula: see text] in comparison with the corresponding analogs. Compared with human cancer cells, the most potent compounds did not show high cytotoxicity against human breast normal MCF-10A cells. Generally, most of the evaluated compounds 6a-l and 7a-o series showed more antitumor activity against SK-BR-3 than MCF-7 cells. Moreover, comparative molecular field analysis (CoMFA) as a popular tools of three-dimensional quantitative structure-activity relationship (3D-QSAR) studies was carried out on 27 spiropyrroloquinolineisoindolinone and spiropyrroloquinolineaza-isoindolinone derivatives with antitumor activity against on SK-BR-3 cells. The obtained CoMFA models showed statistically excellent performance, which also possessed good predictive ability for an external test set. The results confirm the important effect of molecular steric and electrostatic interactions of these compounds on in vitro cytotoxicity against SK-BR-3.

  16. 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.

  17. 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.

  18. 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.

  19. Molecular Imaging and Precision Medicine in Lung Cancer.

    Science.gov (United States)

    Zukotynski, Katherine A; Gerbaudo, Victor H

    2017-01-01

    Precision medicine allows tailoring of preventive or therapeutic interventions to avoid the expense and toxicity of futile treatment given to those who will not respond. Lung cancer is a heterogeneous disease functionally and morphologically. PET is a sensitive molecular imaging technique with a major role in the precision medicine algorithm of patients with lung cancer. It contributes to the precision medicine of lung neoplasia by interrogating tumor heterogeneity throughout the body. It provides anatomofunctional insight during diagnosis, staging, and restaging of the disease. It is a biomarker of tumoral heterogeneity that helps direct selection of the most appropriate treatment, the prediction of early response to cytotoxic and cytostatic therapies, and is a prognostic biomarker in patients with lung cancer. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  20. Vitamin D and colorectal cancer: molecular, epidemiological and clinical evidence.

    Science.gov (United States)

    Dou, Ruoxu; Ng, Kimmie; Giovannucci, Edward L; Manson, JoAnn E; Qian, Zhi Rong; Ogino, Shuji

    2016-05-01

    In many cells throughout the body, vitamin D is converted into its active form calcitriol and binds to the vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D-metabolising enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating the effects of vitamin D. Preclinical and epidemiological studies have provided evidence for anti-cancer effects of vitamin D (particularly against colorectal cancer), although clinical trials have yet to prove its benefit. In addition, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses and clinical trials on vitamin D efficacy in colorectal cancer patients. In this study, we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies and discuss the links and controversies within and between the two parts of evidence.

  1. Molecular biomarkers to guide precision medicine in localized prostate cancer.

    Science.gov (United States)

    Smits, Minke; Mehra, Niven; Sedelaar, Michiel; Gerritsen, Winald; Schalken, Jack A

    2017-08-01

    Major advances through tumor profiling technologies, that include next-generation sequencing, epigenetic, proteomic and transcriptomic methods, have been made in primary prostate cancer, providing novel biomarkers that may guide precision medicine in the near future. Areas covered: The authors provided an overview of novel molecular biomarkers in tissue, blood and urine that may be used as clinical tools to assess prognosis, improve selection criteria for active surveillance programs, and detect disease relapse early in localized prostate cancer. Expert commentary: Active surveillance (AS) in localized prostate cancer is an accepted strategy in patients with very low-risk prostate cancer. Many more patients may benefit from watchful waiting, and include patients of higher clinical stage and grade, however selection criteria have to be optimized and early recognition of transformation from localized to lethal disease has to be improved by addition of molecular biomarkers. The role of non-invasive biomarkers is challenging the need for repeat biopsies, commonly performed at 1 and 4 years in men under AS programs.

  2. Implication of Gastric Cancer Molecular Genetic Markers in Surgical Practice.

    Science.gov (United States)

    Nemtsova, Marina V; Strelnikov, Vladimir V; Tanas, Alexander S; Bykov, Igor I; Zaletaev, Dmitry V; Rudenko, Viktoria V; Glukhov, Alexander I; Kchorobrich, Tatiana V; Li, Yi; Tarasov, Vadim V; Barreto, George E; Aliev, Gjumrakch

    2017-10-01

    We have investigated aberrant methylation of genes CDH1, RASSF1A, MLH1, N33, DAPK, expression of genes hTERT, MMP7, MMP9, BIRC5 (survivin), PTGS2, and activity of telomerase of 106 gastric tumor samples obtained intra-operatively and 53 gastric tumor samples from the same group of patients obtained endoscopically before surgery. Biopsy specimens obtained from 50 patients with chronic calculous cholecystitis were used as a control group. Together with tissue samples obtained from different sites remote to tumors, a total of 727 samples have been studied. The selected parameters comprise a system of molecular markers that can be used in both diagnostics of gastric cancer and in dynamic monitoring of patients after surgery. Special attention was paid to the use of molecular markers for the diagnostics of malignant process in the material obtained endoscopically since the efficacy of morphological diagnostics in biopsies is compromised by intratumoral heterogeneity, which may prevent reliable identification of tumor cells in the sampling. Our data indicated that certain molecular genetic events provided more sensitive yet specific markers of the tumor. We demonstrated that molecular profiles detected in preoperative biopsies were confirmed by the material obtained intra-operatively. The use of endoscopic material facilitates gastric tumors pre-operative diagnostics, improving early detection of gastric cancer and potential effective treatment strategies.

  3. Molecular pathology and prostate cancer therapeutics: from biology to bedside.

    Science.gov (United States)

    Rodrigues, Daniel Nava; Butler, Lisa M; Estelles, David Lorente; de Bono, Johann S

    2014-01-01

    Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men and has an extremely heterogeneous clinical behaviour. The vast majority of PCas are hormonally driven diseases in which androgen signalling plays a central role. The realization that castration-resistant prostate cancer (CRPC) continues to rely on androgen signalling prompted the development of new, effective androgen blocking agents. As the understanding of the molecular biology of PCas evolves, it is hoped that stratification of prostate tumours into distinct molecular entities, each with its own set of vulnerabilities, will be a feasible goal. Around half of PCas harbour rearrangements involving a member of the ETS transcription factor family. Tumours without this rearrangement include SPOP mutant as well as SPINK1-over-expressing subtypes. As the number of targeted therapy agents increases, it is crucial to determine which patients will benefit from these interventions and molecular pathology will be key in this respect. In addition to directly targeting cells, therapies that modify the tumour microenvironment have also been successful in prolonging the lives of PCa patients. Understanding the molecular aspects of PCa therapeutics will allow pathologists to provide core recommendations for patient management. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  4. Molecular subtypes and imaging phenotypes of breast cancer

    International Nuclear Information System (INIS)

    Cho, Nariya

    2016-01-01

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics

  5. Molecular subtypes and imaging phenotypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Nariya Cho

    2016-10-01

    Full Text Available During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2, and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  6. Molecular subtypes and imaging phenotypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nariya [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-08-15

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  7. Molecular analysis of precursor lesions in familial pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Tatjana Crnogorac-Jurcevic

    Full Text Available With less than a 5% survival rate pancreatic adenocarcinoma (PDAC is almost uniformly lethal. In order to make a significant impact on survival of patients with this malignancy, it is necessary to diagnose the disease early, when curative surgery is still possible. Detailed knowledge of the natural history of the disease and molecular events leading to its progression is therefore critical.We have analysed the precursor lesions, PanINs, from prophylactic pancreatectomy specimens of patients from four different kindreds with high risk of familial pancreatic cancer who were treated for histologically proven PanIN-2/3. Thus, the material was procured before pancreatic cancer has developed, rather than from PanINs in a tissue field that already contains cancer. Genome-wide transcriptional profiling using such unique specimens was performed. Bulk frozen sections displaying the most extensive but not microdissected PanIN-2/3 lesions were used in order to obtain the holistic view of both the precursor lesions and their microenvironment. A panel of 76 commonly dysregulated genes that underlie neoplastic progression from normal pancreas to PanINs and PDAC were identified. In addition to shared genes some differences between the PanINs of individual families as well as between the PanINs and PDACs were also seen. This was particularly pronounced in the stromal and immune responses.Our comprehensive analysis of precursor lesions without the invasive component provides the definitive molecular proof that PanIN lesions beget cancer from a molecular standpoint. We demonstrate the need for accumulation of transcriptomic changes during the progression of PanIN to PDAC, both in the epithelium and in the surrounding stroma. An identified 76-gene signature of PDAC progression presents a rich candidate pool for the development of early diagnostic and/or surveillance markers as well as potential novel preventive/therapeutic targets for both familial and sporadic

  8. Exploring the molecular targets of dietary flavonoid fisetin in cancer.

    Science.gov (United States)

    Syed, Deeba N; Adhami, Vaqar Mustafa; Khan, Naghma; Khan, Mohammad Imran; Mukhtar, Hasan

    2016-10-01

    The last few decades have seen a resurgence of interest among the scientific community in exploring the efficacy of natural compounds against various human cancers. Compounds of plant origin belonging to different groups such as alkaloids, flavonoids and polyphenols evaluated for their cancer preventive effects have yielded promising data, thereby offering a potential therapeutic alternative against this deadly disease. The flavonol fisetin (3,3',4',7-tetrahydroxyflavone), present in fruits and vegetables such as strawberries, apple, cucumber, persimmon, grape and onion, was shown to possess anti-microbial, anti-inflammatory, anti-oxidant and more significantly anti-carcinogenic activity when assessed in diverse cell culture and animal model systems. The purpose of this review is to update and discuss key findings obtained till date from in vitro and in vivo studies on fisetin, with special focus on its anti-cancer role. The molecular mechanism(s) described in the observed growth inhibitory effects of fisetin in different cancer cell types is also summarized. Moreover, an attempt is made to delineate the direction of future studies that could lead to the development of fisetin as a potent chemopreventive/chemotherapeutic agent against cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Epigenetic: a molecular link between testicular cancer and environmental exposures?

    Directory of Open Access Journals (Sweden)

    Aurelie eVega

    2012-11-01

    Full Text Available In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters (EDs exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the Testicular Dysgenesis Syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Futhermore, infertility has been stated as a risk factor for testicular cancer. The incidence of testicular cancer has been increasing over the past decades. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ (CIS from fetal germ cells (primordial germ cell or gonocyte. During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications plays an important role in normal development as well as in various diseases, including testicular cancer.Here we will review chromatin modifications which can affect testicular physiology leading to the development of testicular cancer; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

  10. Twists and turns in life and science. Foundation Series in Cancer Research

    Czech Academy of Sciences Publication Activity Database

    Svoboda, Jan

    2008-01-01

    Roč. 99, č. 1 (2008), s. 1-32 ISSN 0065-230X Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z50520514 Keywords : cancer * oncogene * src Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.721, year: 2008

  11. Molecular Targets for Radiation Oncology in Prostate Cancer

    International Nuclear Information System (INIS)

    Wang, Tao; Languino, Lucia R.; Lian, Jane; Stein, Gary; Blute, Michael; FitzGerald, Thomas J.

    2011-01-01

    Recent selected developments of the molecular science of prostate cancer (PrCa) biology and radiation oncology are reviewed. We present potential targets for molecular integration treatment strategies with radiation therapy (RT), and highlight potential strategies for molecular treatment in combination with RT for patient care. We provide a synopsis of the information to date regarding molecular biology of PrCa, and potential integrated research strategy for improved treatment of PrCa. Many patients with early-stage disease at presentation can be treated effectively with androgen ablation treatment, surgery, or RT. However, a significant portion of men are diagnosed with advanced stage/high-risk disease and these patients progress despite curative therapeutic intervention. Unfortunately, management options for these patients are limited and are not always successful including treatment for hormone refractory disease. In this review, we focus on molecules of extracellular matrix component, apoptosis, androgen receptor, RUNX, and DNA methylation. Expanding our knowledge of the molecular biology of PrCa will permit the development of novel treatment strategies integrated with RT to improve patient outcome

  12. Guidance for laboratories performing molecular pathology for cancer patients

    Science.gov (United States)

    Cree, Ian A; Deans, Zandra; Ligtenberg, Marjolijn J L; Normanno, Nicola; Edsjö, Anders; Rouleau, Etienne; Solé, Francesc; Thunnissen, Erik; Timens, Wim; Schuuring, Ed; Dequeker, Elisabeth; Murray, Samuel; Dietel, Manfred; Groenen, Patricia; Van Krieken, J Han

    2014-01-01

    Molecular testing is becoming an important part of the diagnosis of any patient with cancer. The challenge to laboratories is to meet this need, using reliable methods and processes to ensure that patients receive a timely and accurate report on which their treatment will be based. The aim of this paper is to provide minimum requirements for the management of molecular pathology laboratories. This general guidance should be augmented by the specific guidance available for different tumour types and tests. Preanalytical considerations are important, and careful consideration of the way in which specimens are obtained and reach the laboratory is necessary. Sample receipt and handling follow standard operating procedures, but some alterations may be necessary if molecular testing is to be performed, for instance to control tissue fixation. DNA and RNA extraction can be standardised and should be checked for quality and quantity of output on a regular basis. The choice of analytical method(s) depends on clinical requirements, desired turnaround time, and expertise available. Internal quality control, regular internal audit of the whole testing process, laboratory accreditation, and continual participation in external quality assessment schemes are prerequisites for delivery of a reliable service. A molecular pathology report should accurately convey the information the clinician needs to treat the patient with sufficient information to allow for correct interpretation of the result. Molecular pathology is developing rapidly, and further detailed evidence-based recommendations are required for many of the topics covered here. PMID:25012948

  13. Identifying molecular targets of lifestyle modifications in colon cancer prevention

    Directory of Open Access Journals (Sweden)

    Molly Marie Derry

    2013-05-01

    Full Text Available One in four deaths in the United States is cancer-related, and colorectal cancer (CRC is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; ~20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological and behavioral processes that could positively influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.

  14. Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

    Science.gov (United States)

    Subramaniam, Prasad

    Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on

  15. Vitamin D and Colorectal Cancer: Molecular, Epidemiological, and Clinical Evidence

    Science.gov (United States)

    Dou, Ruoxu; Ng, Kimmie; Giovannucci, Edward L.; Manson, JoAnn E.; Qian, Zhi Rong; Ogino, Shuji

    2016-01-01

    In many cells throughout the body, vitamin D is converted into its active form calcitriol, and binds to vitamin D receptor (VDR), which functions as a transcription factor to regulate various biological processes including cellular differentiation and immune response. Vitamin D metabolizing enzymes (including CYP24A1 and CYP27B1) and VDR play major roles in exerting and regulating effects of vitamin D. Preclinical and epidemiological studies provide evidence for anticancer effects of vitamin D (in particular, against colorectal cancer), though clinical trials have yet to prove its benefit. Additionally, molecular pathological epidemiology research can provide insights into the interaction of vitamin D with tumour molecular and immunity status. Other future research directions include genome-wide research on VDR transcriptional targets, gene-environment interaction analyses, and clinical trials on vitamin D efficacy in colorectal cancer patients. Here we review the literature on vitamin D and colorectal cancer from both mechanistic and population studies, and discuss the links and controversies within and between the two parts of evidence. PMID:27245104

  16. The pathology of familial breast cancer: Immunohistochemistry and molecular analysis

    International Nuclear Information System (INIS)

    Osin, Pinchas P; Lakhani, Sunil R

    1999-01-01

    Extensive studies of BRCA1- and BRCA2-associated breast tumours have been carried out in the few years since the identification of these familial breast cancer predisposing genes. The morphological studies suggest that BRCA1 tumours differ from BRCA2 tumours and from sporadic breast cancers. Recent progress in immunohistochemistry and molecular biology techniques has enabled in-depth investigation of molecular pathology of these tumours. Studies to date have investigated issues such as steroid hormone receptor expression, mutation status of tumour suppressor genes TP53 and c-erbB2, and expression profiles of cell cycle proteins p21, p27 and cyclin D 1 . Despite relative paucity of data, strong evidence of unique biological characteristics of BRCA1-associated breast cancer is accumulating. BRCA1-associated tumours appear to show an increased frequency of TP53 mutations, frequent p53 protein stabilization and absence of imunoreactivity for steroid hormone receptors. Further studies of larger number of samples of both BRCA1- and BRCA2-associated tumours are necessary to clarify and confirm these observations

  17. Asymptotic behaviour of optimal fraction-rational series of the perturbation theory at description of molecular rotational spectra

    International Nuclear Information System (INIS)

    Burenin, A.V.

    1994-01-01

    A possibility is shown of substantial expansion of the choice of asymptotic behaviour of optimal fraction-rational series of the perturbation theory on description of molecular rotational spectra. The expansion permits to hope for substantial improvement of results of using the conception of effective rotational hamiltonian in a fraction-rational form on the description of highly perturbed vibrational states

  18. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  19. Molecular epidemiological study of human rectal cancer induced by radiotherapy

    International Nuclear Information System (INIS)

    Rytomaa, T.; Servomaa, K.; Kiuru, A.; Auvinen, A.; Makkonen, K.; Kosma, V.M.; Hirvikoski, P.

    1997-01-01

    In the present molecular epidemiological study we have examined possible presence of characteristic radiation-associated mutations in the p53 and K-ras genes in secondary rectal cancers in 67 female radiotherapy patients, compared with primary rectal cancers in 67 matched controls Exons 4-8 of the p53 and K-ras gen were amplified from histological sections, and screened for mutations by SSCP and direct sequencing. The results showed that p53 and K-ras gene mutations were very uncommon in apparent radiation-induced tumours compared with matched controls. This may, by itself, be a hallmark of high-dose radiation damage, but it also suggests that genes other than p53 and K-ras are critical in female rectal carcinogenesis associated with radiation exposure. (authors)

  20. [Molecular characterization of breast cancer in clinical practice].

    Science.gov (United States)

    Zemmouri, Y; De Croze, D; Vincent Salomon, A; Rouzier, R; Bonneau, C

    2016-05-01

    Breast cancer involves various types of tumors. The objective of this review was to provide a summary of the main methods currently available in clinical practice to characterize breast cancers at a molecular level and to discuss their prognostic and predictive values. Hormonal receptors expression and the HER2 status are prognostic markers and can also predict the response to targeted therapies. Their analysis through immunohistochemistry is systematical. Ki67 is an effective prognostic marker, but its reliability is debated because of its low reproducibility between laboratories and between pathologists. Commercial genomic signatures are all considered valid prognostic tools and may guide physicians to make therapeutic choices. These signatures are costly and should therefore be restricted to situations in which the use of chemotherapy remains equivocal. Copyright © 2016. Published by Elsevier SAS.

  1. Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial.

    Science.gov (United States)

    Chantrill, Lorraine A; Nagrial, Adnan M; Watson, Clare; Johns, Amber L; Martyn-Smith, Mona; Simpson, Skye; Mead, Scott; Jones, Marc D; Samra, Jaswinder S; Gill, Anthony J; Watson, Nicole; Chin, Venessa T; Humphris, Jeremy L; Chou, Angela; Brown, Belinda; Morey, Adrienne; Pajic, Marina; Grimmond, Sean M; Chang, David K; Thomas, David; Sebastian, Lucille; Sjoquist, Katrin; Yip, Sonia; Pavlakis, Nick; Asghari, Ray; Harvey, Sandra; Grimison, Peter; Simes, John; Biankin, Andrew V

    2015-05-01

    Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies. The pilot stage of the IMPaCT trial assessed the feasibility of acquiring suitable tumor specimens for molecular analysis and returning high-quality actionable genomic data within a clinically acceptable timeframe. We screened for three molecular targets: HER2 amplification; KRAS wild-type; and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM). Tumor biopsy and archived tumor samples were collected from 93 patients and 76 were screened. To date 22 candidate cases have been identified: 14 KRAS wild-type, 5 cases of HER2 amplification, 2 mutations in BRCA2, and 1 ATM mutation. Median time from consent to the return of validated results was 21.5 days. An inability to obtain a biopsy or insufficient tumor content in the available specimen were common reasons for patient exclusion from molecular analysis while deteriorating performance status prohibited a number of patients from proceeding in the study. Documenting the feasibility of acquiring and screening biospecimens for actionable molecular targets in real time will aid other groups embarking on similar trials. Key elements include the need to better prescreen patients, screen more patients, and offer more attractive clinical trial options. ©2015 American Association for Cancer Research.

  2. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bournet, Barbara [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome [INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Buscail, Louis, E-mail: buscail.l@chu-toulouse.fr [Department of Gastroenterology, University Hospital Center Rangueil, 1 avenue Jean Poulhès, TSA 50032, 31059 Toulouse Cedex 9 (France); INSERM U1037, University Hospital Center Rangueil, Toulouse (France); Cordelier, Pierre [INSERM U1037, University Hospital Center Rangueil, Toulouse (France)

    2011-02-24

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer.

  3. 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.

  4. Molecular Endoscopic Ultrasound for Diagnosis of Pancreatic Cancer

    International Nuclear Information System (INIS)

    Bournet, Barbara; Pointreau, Adeline; Delpu, Yannick; Selves, Janick; Torrisani, Jerome; Buscail, Louis; Cordelier, Pierre

    2011-01-01

    Endoscopic ultrasound-guided fine needle aspiration-biopsy is a safe and effective technique in diagnosing and staging of pancreatic ductal adenocarcinoma. However its predictive negative value does not exceed 50% to 60%. Unfortunately, the majority of pancreatic cancer patients have a metastatic and/or a locally advanced disease (i.e., not eligible for curative resection) which explains the limited access to pancreatic tissue specimens. Endoscopic ultrasound-guided fine needle aspiration-biopsy is the most widely used approach for cytological and histological material sampling in these situations used in up to two thirds of patients with pancreatic cancer. Based on this unique material, we and others developed strategies to improve the differential diagnosis between carcinoma and inflammatory pancreatic lesions by analysis of KRAS oncogene mutation, microRNA expression and methylation, as well as mRNA expression using both qRT-PCR and Low Density Array Taqman analysis. Indeed, differentiating pancreatic cancer from pseudotumoral chronic pancreatitis remains very difficult in current clinical practice, and endoscopic ultrasound-guided fine needle aspiration-biopsy analysis proved to be very helpful. In this review, we will compile the clinical and molecular advantages of using endoscopic ultrasound-guided fine needle aspiration-biopsy in managing pancreatic cancer

  5. Molecular Mechanisms of Anticancer Effects of Phytoestrogens in Breast Cancer.

    Science.gov (United States)

    Hsieh, Chia-Jung; Hsu, Ya-Ling; Huang, Ya-Fang; Tsai, Eing-Mei

    2018-01-01

    Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. Chemopreventive properties of phytoestrogens have emerged from epidemiological observations. In recent clinical research studies, phytoestrogens are safe and may even protect against breast cancer. In this brief review, the molecular mechanisms of phytoestrogens on regulation of cell cycle, apoptosis, estrogen receptors, cell signaling pathways, and epigenetic modulations in relation to breast cancer are discussed. Phytoestrogens have a preferential affinity for estrogen receptor (ER)-β, which appears to be associated with antiproliferative and anticarcinogenic effects. Moreover, while phytoestrogens not only inhibit ER-positive but also ER-negative breast cancer cells, the possibility of epigenetic modulation playing an important role is also discussed. In conclusion, as there are multiple targets and actions of phytoestrogens, extensive research is still necessary. However, due to low toxicity, low cost, and easy availability, their potent chemoprevention effects deserve further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Current and future molecular diagnostics in non-small-cell lung cancer.

    Science.gov (United States)

    Li, Chun Man; Chu, Wing Ying; Wong, Di Lun; Tsang, Hin Fung; Tsui, Nancy Bo Yin; Chan, Charles Ming Lok; Xue, Vivian Wei Wen; Siu, Parco Ming Fai; Yung, Benjamin Yat Ming; Chan, Lawrence Wing Chi; Wong, Sze Chuen Cesar

    2015-01-01

    The molecular investigation of lung cancer has opened up an advanced area for the diagnosis and therapeutic management of lung cancer patients. Gene alterations in cancer initiation and progression provide not only information on molecular changes in lung cancer but also opportunities in advanced therapeutic regime by personalized targeted therapy. EGFR mutations and ALK rearrangement are important predictive biomarkers for the efficiency of tyrosine kinase inhibitor treatment in lung cancer patients. Moreover, epigenetic aberration and microRNA dysregulation are recent advances in the early detection and monitoring of lung cancer. Although a wide range of molecular tests are available, standardization and validation of assay protocols are essential for the quality of the test outcome. In this review, current and new advancements of molecular biomarkers for non-small-cell lung cancer will be discussed. Recommendations on future development of molecular diagnostic services will also be explored.

  7. Molecular Imaging and Precision Medicine in Uterine and Ovarian Cancers.

    Science.gov (United States)

    Zukotynski, Katherine A; Kim, Chun K

    2017-10-01

    Gynecologic cancer is a heterogeneous group of diseases both functionally and morphologically. Today, PET coupled with computed tomography (PET/CT) or PET/MR imaging play a central role in the precision medicine algorithm of patients with gynecologic malignancy. In particular, PET/CT and PET/MR imaging are molecular imaging techniques that not only are useful tools for initial staging and restaging but provide anatomofunctional insight and can serve as predictive and prognostic biomarkers of response in patients with gynecologic malignancy. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Molecular biology-based diagnosis and therapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Fujita, Hayato; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Tanaka, Masao

    2011-01-01

    Mainly described are author's investigations of the title subject through clinical and basic diagnosis/therapeutic approach. Based on their consideration of carcinogenesis and pathological features of pancreatic cancer (PC), analysis of expression of cancer-related genes in clinically available samples like pancreatic juice and cells biopsied can result in attaining their purposes. Desmoplasia, a pathological feature of PC, possibly induces resistance to therapy and one of strategies is probably its suppression. Targeting stem cells of the mesenchyma as well as those of PC is also a strategy in future. Authors' studies have revealed that quantitation of hTERT (coding teromerase) mRNA levels in PC cells micro-dissected from cytological specimens is an accurate molecular biological diagnostic method applicable clinically. Other cancer-related genes are also useful for the diagnosis and mucin (MUC) family genes are shown to be typical ones for differentiating the precancerous PC, PC and chronic pancreatisis. Efficacy of standard gemcitabine chemotherapy can be individualized with molecular markers concerned to metabolism of the drug like dCK. Radiotherapy/radio-chemotherapy are not so satisfactory for PC treatment now. Authors have found elevated MMP-2 expression and HGF/c-Met signal activation in irradiated PC cells, which can increase the invasive capability; and stimulation of phosphorylation and activation of c-Met/MARK in co-culture of irradiated PC cells with messenchymal cells from PC, which possibly leads to progression of malignancy of PC through their interaction, of which suppression, therefore, can be a new approach to increase the efficacy of radiotherapy. Authors are making effort to introducing adenovirus therapy in clinic; exempli gratia (e.g.), the virus carrying wild type p53, a cancer-suppressive gene, induces apoptosis of PC cells often having its mutated gene. (T.T.)

  9. Cancer Stem Cells and Molecular Biology Test in Colorectal Cancer: Therapeutic Implications.

    Science.gov (United States)

    Effendi-Ys, Rustam

    2017-10-01

    Colorectal cancer (CRC) is the third most frequent cancer in males, the second in females, and is the second leading cause of cancer related death worldwide. Within Indonesia's 250 million population, the incidence rates for CRC per 100,000 population were 15.2 for males and 10.2 for females, and estimated 63,500 cases per year.  More than 50% of colorectal cancer patients will develop metastasis. CRC is still the main cause of tumor-related death, and although most CRC patients are treated with surgery to remove the tumor tissue, some of the CRC patients recurred. Chemotherapy used as adjuvant or neoadjuvant therapy also has several problems, in which these treatments are useless in tumor cells with chemo-resistance. Molecular testing of CRC from tumor tissues has important implications for the selection of treatment. Biomarkers can be used as prognostic value, molecular predictive factors, and targeted therapy. Recent research reported that, cancer stem cells (CSCs) are considered as the origin of tumorigenesis, development, metastasis and recurrence. At present, it has been shown that CSCs existed in many tumors including CRC. This review aims to summarize the issue on CSCs, and the future development of drugs that target colorectal cancer stem cells.

  10. Molecular imaging of tumor blood vessels in prostate cancer.

    Science.gov (United States)

    Tilki, Derya; Seitz, Michael; Singer, Bernhard B; Irmak, Ster; Stief, Christian G; Reich, Oliver; Ergün, Süleyman

    2009-05-01

    In the past three decades many efforts have been undertaken to understand the mechanisms of tumor angiogenesis. The introduction of anti-angiogenic drugs in tumor therapy during the last few years necessitates the establishment of new techniques enabling molecular imaging of tumor vascular remodelling. The determination of tumor size as commonly used is not appropriate since the extended necrosis under anti-angiogenic therapy does not necessarily result in the reduction of tumor diameter. The basis for the molecular imaging of tumor blood vessels is the remodelling of the tumor vessels under anti-angiogenic therapy which obviously occurs at an early stage and seems to be a convincing parameter. Beside the enormous progress in this field during the last few years the resolution is still not high enough to evaluate the remodelling of the micro tumor vessels. New imaging approaches combining specific molecular markers for tumor vessels with the different imaging techniques are needed to overcome this issue as exemplarily discussed for prostate cancer in this review. Molecular contrast agents targeting the vasculature will allow clinicians the visualization of vascular remodelling processes taking place under anti-angiogenic therapy and improve tumor diagnosis and follow-up.

  11. Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0737 TITLE: Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer PRINCIPAL...AND SUBTITLE 5a. CONTRACT NUMBER Developing a PTEN-ERG Signature to Improve Molecular Risk Stratification in Prostate Cancer 5b. GRANT NUMBER W81XWH...that there exist distinctive molecular correlates of PTEN loss in the context of ETS-negative versus ETS-positive human prostate cancers and that

  12. Molecular Characterization of ERα-positive and Triple Negative Breast Cancer

    NARCIS (Netherlands)

    Severson, T.M.

    2016-01-01

    Breast cancer, one of the most common of all cancers, is diagnosed in over 1.5 million people world-wide each year. Overall, treatments for breast cancer are considered relatively successful, however recurrence is a clinical problem of paramount importance. Molecular subtypes of breast cancer,

  13. Molecular profiling of cancer--the future of personalized cancer medicine: a primer on cancer biology and the tools necessary to bring molecular testing to the clinic.

    Science.gov (United States)

    Stricker, Thomas; Catenacci, Daniel V T; Seiwert, Tanguy Y

    2011-04-01

    Cancers arise as a result of an accumulation of genetic aberrations that are either acquired or inborn. Virtually every cancer has its unique set of molecular changes. Technologies have been developed to study cancers and derive molecular characteristics that increasingly have implications for clinical care. Indeed, the identification of key genetic aberrations (molecular drivers) may ultimately translate into dramatic benefit for patients through the development of highly targeted therapies. With the increasing availability of newer, more powerful, and cheaper technologies such as multiplex mutational screening, next generation sequencing, array-based approaches that can determine gene copy numbers, methylation, expression, and others, as well as more sophisticated interpretation of high-throughput molecular information using bioinformatics tools like signatures and predictive algorithms, cancers will routinely be characterized in the near future. This review examines the background information and technologies that clinicians and physician-scientists will need to interpret in order to develop better, personalized treatment strategies. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Online Series presents Cancer Prevention Through Immunomodulation. Does Diet Play a Role? | Division of Cancer Prevention

    Science.gov (United States)

    Scientists are increasingly harnessing the power of the immune system to prevent cancer. Nutrition provides an opportunity for a generalized immune activation and reduction of cancer risk in certain populations. Research on several foods and bioactive food components as immunologic modulators is showing promising results. |

  15. Time series analyses of breathing patterns of lung cancer patients using nonlinear dynamical system theory.

    Science.gov (United States)

    Tewatia, D K; Tolakanahalli, R P; Paliwal, B R; Tomé, W A

    2011-04-07

    The underlying requirements for successful implementation of any efficient tumour motion management strategy are regularity and reproducibility of a patient's breathing pattern. The physiological act of breathing is controlled by multiple nonlinear feedback and feed-forward couplings. It would therefore be appropriate to analyse the breathing pattern of lung cancer patients in the light of nonlinear dynamical system theory. The purpose of this paper is to analyse the one-dimensional respiratory time series of lung cancer patients based on nonlinear dynamics and delay coordinate state space embedding. It is very important to select a suitable pair of embedding dimension 'm' and time delay 'τ' when performing a state space reconstruction. Appropriate time delay and embedding dimension were obtained using well-established methods, namely mutual information and the false nearest neighbour method, respectively. Establishing stationarity and determinism in a given scalar time series is a prerequisite to demonstrating that the nonlinear dynamical system that gave rise to the scalar time series exhibits a sensitive dependence on initial conditions, i.e. is chaotic. Hence, once an appropriate state space embedding of the dynamical system has been reconstructed, we show that the time series of the nonlinear dynamical systems under study are both stationary and deterministic in nature. Once both criteria are established, we proceed to calculate the largest Lyapunov exponent (LLE), which is an invariant quantity under time delay embedding. The LLE for all 16 patients is positive, which along with stationarity and determinism establishes the fact that the time series of a lung cancer patient's breathing pattern is not random or irregular, but rather it is deterministic in nature albeit chaotic. These results indicate that chaotic characteristics exist in the respiratory waveform and techniques based on state space dynamics should be employed for tumour motion management.

  16. Time series analyses of breathing patterns of lung cancer patients using nonlinear dynamical system theory

    Energy Technology Data Exchange (ETDEWEB)

    Tewatia, D K; Tolakanahalli, R P; Paliwal, B R; Tome, W A, E-mail: tewatia@wisc.edu [Department of Human Oncology, University of Wisconsin, Madison, WI (United States)

    2011-04-07

    The underlying requirements for successful implementation of any efficient tumour motion management strategy are regularity and reproducibility of a patient's breathing pattern. The physiological act of breathing is controlled by multiple nonlinear feedback and feed-forward couplings. It would therefore be appropriate to analyse the breathing pattern of lung cancer patients in the light of nonlinear dynamical system theory. The purpose of this paper is to analyse the one-dimensional respiratory time series of lung cancer patients based on nonlinear dynamics and delay coordinate state space embedding. It is very important to select a suitable pair of embedding dimension 'm' and time delay '{tau}' when performing a state space reconstruction. Appropriate time delay and embedding dimension were obtained using well-established methods, namely mutual information and the false nearest neighbour method, respectively. Establishing stationarity and determinism in a given scalar time series is a prerequisite to demonstrating that the nonlinear dynamical system that gave rise to the scalar time series exhibits a sensitive dependence on initial conditions, i.e. is chaotic. Hence, once an appropriate state space embedding of the dynamical system has been reconstructed, we show that the time series of the nonlinear dynamical systems under study are both stationary and deterministic in nature. Once both criteria are established, we proceed to calculate the largest Lyapunov exponent (LLE), which is an invariant quantity under time delay embedding. The LLE for all 16 patients is positive, which along with stationarity and determinism establishes the fact that the time series of a lung cancer patient's breathing pattern is not random or irregular, but rather it is deterministic in nature albeit chaotic. These results indicate that chaotic characteristics exist in the respiratory waveform and techniques based on state space dynamics should be employed

  17. Time series analyses of breathing patterns of lung cancer patients using nonlinear dynamical system theory

    International Nuclear Information System (INIS)

    Tewatia, D K; Tolakanahalli, R P; Paliwal, B R; Tome, W A

    2011-01-01

    The underlying requirements for successful implementation of any efficient tumour motion management strategy are regularity and reproducibility of a patient's breathing pattern. The physiological act of breathing is controlled by multiple nonlinear feedback and feed-forward couplings. It would therefore be appropriate to analyse the breathing pattern of lung cancer patients in the light of nonlinear dynamical system theory. The purpose of this paper is to analyse the one-dimensional respiratory time series of lung cancer patients based on nonlinear dynamics and delay coordinate state space embedding. It is very important to select a suitable pair of embedding dimension 'm' and time delay 'τ' when performing a state space reconstruction. Appropriate time delay and embedding dimension were obtained using well-established methods, namely mutual information and the false nearest neighbour method, respectively. Establishing stationarity and determinism in a given scalar time series is a prerequisite to demonstrating that the nonlinear dynamical system that gave rise to the scalar time series exhibits a sensitive dependence on initial conditions, i.e. is chaotic. Hence, once an appropriate state space embedding of the dynamical system has been reconstructed, we show that the time series of the nonlinear dynamical systems under study are both stationary and deterministic in nature. Once both criteria are established, we proceed to calculate the largest Lyapunov exponent (LLE), which is an invariant quantity under time delay embedding. The LLE for all 16 patients is positive, which along with stationarity and determinism establishes the fact that the time series of a lung cancer patient's breathing pattern is not random or irregular, but rather it is deterministic in nature albeit chaotic. These results indicate that chaotic characteristics exist in the respiratory waveform and techniques based on state space dynamics should be employed for tumour motion management.

  18. Surgical staging identified false HPV-negative cases in a large series of invasive cervical cancers.

    Science.gov (United States)

    Petry, Karl Ulrich; Liebrich, Clemens; Luyten, Alexander; Zander, Martina; Iftner, Thomas

    2017-12-01

    We examined a large series of biopsy-proven invasive cervical cancers with surgical staging and HPV re-testing to estimate the relevance of HPV-negative cervical cancers in a Caucasian population. We prospectively collected smears from 371 patients with a biopsy-proven diagnosis of cervical cancer for HC2 testing of high-risk HPV (HR-HPV). In HC2-negative cases, smears and paraffin embedded tissue blocks underwent additional HPV genotyping. HC2 tests showed 31/371 cases (8.8%) had negative findings. Surgical staging showed that 21/31 HC2-negative cases (68%) were not cervical cancer. Overall, 340/350 cases of primary cervical cancer confirmed by surgical staging tested HC2 positive (97.2%). Non-high-risk HPV subtypes were detected in five cases (one HPV-53, one HPV-70, and three HPV-73) and high-risk subtypes in four patients with HC2-negative cervical cancer (two HPV 16 and two HPV-18). The remaining case, a primary undifferentiated carcinoma of the uterine cervix, tested negative for HPV-DNA with all tests. The main explanation for HPV-negative cervical cancer was a false diagnosis, followed by cancers associated with non-HR-HPV types, and false-negative HR-HPV results. Truly HPV negative seem to be very rare in Caucasian populations. Retrospective analyses without surgical staging may overestimate the proportion of HPV negative cervical cancers. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Colorectal Cancer in Iran: Molecular Epidemiology and Screening Strategies

    Directory of Open Access Journals (Sweden)

    Roya Dolatkhah

    2015-01-01

    Full Text Available Purpose. The increasing incidence of colorectal cancer (CRC in the past three decades in Iran has made it a major public health burden. This study aimed to report its epidemiologic features, molecular genetic aspects, survival, heredity, and screening pattern in Iran. Methods. A comprehensive literature review was conducted to identify the relevant published articles. We used medical subject headings, including colorectal cancer, molecular genetics, KRAS and BRAF mutations, screening, survival, epidemiologic study, and Iran. Results. Age standardized incidence rate of Iranian CRCs was 11.6 and 10.5 for men and women, respectively. Overall five-year survival rate was 41%, and the proportion of CRC among the younger age group was higher than that of western countries. Depending on ethnicity, geographical region, dietary, and genetic predisposition, mutation genes were considerably diverse and distinct among CRCs across Iran. The high occurrence of CRC in records of relatives of CRC patients showed that family history of CRC was more common among young CRCs. Conclusion. Appropriate screening strategies for CRC which is amenable to early detection through screening, especially in relatives of CRCs, should be considered as the first step in CRC screening programs.

  20. Colorectal Cancer in Iran: Molecular Epidemiology and Screening Strategies

    International Nuclear Information System (INIS)

    Dolatkhah, R.; Somi, M. H.; Dolatkhah, R.; Kermani, I. A.; Dastgiri, S.

    2015-01-01

    The increasing incidence of colorectal cancer (CRC) in the past three decades in Iran has made it a major public health burden. This study aimed to report its epidemiologic features, molecular genetic aspects, survival, heredity, and screening pattern in Iran. Methods. A comprehensive literature review was conducted to identify the relevant published articles. We used medical subject headings, including colorectal cancer, molecular genetics, KRAS and BRAF mutations, screening, survival, epidemiologic study, and Iran. Results. Age standardized incidence rate of Iranian CRCs was 11.6 and 10.5 for men and women, respectively. Overall five-year survival rate was 41%, and the proportion of CRC among the younger age group was higher than that of western countries. Depending on ethnicity, geographical region, dietary, and genetic predisposition, mutation genes were considerably diverse and distinct among CRCs across Iran. The high occurrence of CRC in records of relatives of CRC patients showed that family history of CRC was more common among young CRCs. Conclusion. Appropriate screening strategies for CRC which is amenable to early detection through screening, especially in relatives of CRCs, should be considered as the first step in CRC screening programs.

  1. MOLECULAR BIOLOGICAL FACTORS IN THE PREDICTION OF PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    S. V. Vtorushin

    2017-01-01

    Full Text Available Purpose: to review the available data on molecular-genetic diagnostic and prognostic markers in prostate cancer. Material and methods. The following electronic databases were used for our systematic review: Medline, Cochrane Library and Elibrary. Of 540 studies, 61 were used for our systematic review. Results. There are currently a variety of both prognostic and diagnostic markers used for diagnosis and treatment of prostate cancer. The review presents the classification of markers depending on the method and medium in which they were identified. The molecular mechanisms of participation of the different genes and proteins in the pathogenesis and progression of prostate carcinoma were analyzed and the potential importance of their use in clinical practice was provided. Conclusion. Many of the existing markers can be used for screening and early detection of tumors, and they have been proved to have a prognostic value. However, contradictory findings with regard to certain proteins and genes require further study, their validation with the subsequent implementation into clinical practice.

  2. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer.

    Science.gov (United States)

    Ciriello, Giovanni; Gatza, Michael L; Beck, Andrew H; Wilkerson, Matthew D; Rhie, Suhn K; Pastore, Alessandro; Zhang, Hailei; McLellan, Michael; Yau, Christina; Kandoth, Cyriac; Bowlby, Reanne; Shen, Hui; Hayat, Sikander; Fieldhouse, Robert; Lester, Susan C; Tse, Gary M K; Factor, Rachel E; Collins, Laura C; Allison, Kimberly H; Chen, Yunn-Yi; Jensen, Kristin; Johnson, Nicole B; Oesterreich, Steffi; Mills, Gordon B; Cherniack, Andrew D; Robertson, Gordon; Benz, Christopher; Sander, Chris; Laird, Peter W; Hoadley, Katherine A; King, Tari A; Perou, Charles M

    2015-10-08

    Invasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features. PTEN loss associated with increased AKT phosphorylation, which was highest in ILC among all breast cancer subtypes. Spatially clustered FOXA1 mutations correlated with increased FOXA1 expression and activity. Conversely, GATA3 mutations and high expression characterized luminal A IDC, suggesting differential modulation of ER activity in ILC and IDC. Proliferation and immune-related signatures determined three ILC transcriptional subtypes associated with survival differences. Mixed IDC/ILC cases were molecularly classified as ILC-like and IDC-like revealing no true hybrid features. This multidimensional molecular atlas sheds new light on the genetic bases of ILC and provides potential clinical options. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Molecular markers in bladder cancer: Novel research frontiers.

    Science.gov (United States)

    Sanguedolce, Francesca; Cormio, Antonella; Bufo, Pantaleo; Carrieri, Giuseppe; Cormio, Luigi

    2015-01-01

    Bladder cancer (BC) is a heterogeneous disease encompassing distinct biologic features that lead to extremely different clinical behaviors. In the last 20 years, great efforts have been made to predict disease outcome and response to treatment by developing risk assessment calculators based on multiple standard clinical-pathological factors, as well as by testing several molecular markers. Unfortunately, risk assessment calculators alone fail to accurately assess a single patient's prognosis and response to different treatment options. Several molecular markers easily assessable by routine immunohistochemical techniques hold promise for becoming widely available and cost-effective tools for a more reliable risk assessment, but none have yet entered routine clinical practice. Current research is therefore moving towards (i) identifying novel molecular markers; (ii) testing old and new markers in homogeneous patients' populations receiving homogeneous treatments; (iii) generating a multimarker panel that could be easily, and thus routinely, used in clinical practice; (iv) developing novel risk assessment tools, possibly combining standard clinical-pathological factors with molecular markers. This review analyses the emerging body of literature concerning novel biomarkers, ranging from genetic changes to altered expression of a huge variety of molecules, potentially involved in BC outcome and response to treatment. Findings suggest that some of these indicators, such as serum circulating tumor cells and tissue mitochondrial DNA, seem to be easily assessable and provide reliable information. Other markers, such as the phosphoinositide-3-kinase (PI3K)/AKT (serine-threonine kinase)/mTOR (mammalian target of rapamycin) pathway and epigenetic changes in DNA methylation seem to not only have prognostic/predictive value but also, most importantly, represent valuable therapeutic targets. Finally, there is increasing evidence that the development of novel risk assessment tools

  4. Validation of a Radiosensitivity Molecular Signature in Breast Cancer

    Science.gov (United States)

    Eschrich, Steven A.; Fulp, William J.; Pawitan, Yudi; Foekens, John A.; Smid, Marcel; Martens, John W. M.; Echevarria, Michelle; Kamath, Vidya; Lee, Ji-Hyun; Harris, Eleanor E.; Bergh, Jonas; Torres-Roca, Javier F.

    2014-01-01

    Purpose Previously, we developed a radiosensitivity molecular signature (RSI) that was clinically-validated in three independent datasets (rectal, esophageal, head and neck) in 118 patients. Here, we test RSI in radiotherapy (RT) treated breast cancer patients. Experimental Design RSI was tested in two previously published breast cancer datasets. Patients were treated at the Karolinska University Hospital (n=159) and Erasmus Medical Center (n=344). RSI was applied as previously described. Results We tested RSI in RT-treated patients (Karolinska). Patients predicted to be radiosensitive (RS) had an improved 5 yr relapse-free survival when compared with radioresistant (RR) patients (95% vs. 75%, p=0.0212) but there was no difference between RS/RR patients treated without RT (71% vs. 77%, p=0.6744), consistent with RSI being RT-specific (interaction term RSIxRT, p=0.05). Similarly, in the Erasmus dataset RT-treated RS patients had an improved 5-year distant-metastasis-free survival over RR patients (77% vs. 64%, p=0.0409) but no difference was observed in patients treated without RT (RS vs. RR, 80% vs. 81%, p=0.9425). Multivariable analysis showed RSI is the strongest variable in RT-treated patients (Karolinska, HR=5.53, p=0.0987, Erasmus, HR=1.64, p=0.0758) and in backward selection (removal alpha of 0.10) RSI was the only variable remaining in the final model. Finally, RSI is an independent predictor of outcome in RT-treated ER+ patients (Erasmus, multivariable analysis, HR=2.64, p=0.0085). Conclusions RSI is validated in two independent breast cancer datasets totaling 503 patients. Including prior data, RSI is validated in five independent cohorts (621 patients) and represents, to our knowledge, the most extensively validated molecular signature in radiation oncology. PMID:22832933

  5. Hybrid analysis for indicating patients with breast cancer using temperature time series.

    Science.gov (United States)

    Silva, Lincoln F; Santos, Alair Augusto S M D; Bravo, Renato S; Silva, Aristófanes C; Muchaluat-Saade, Débora C; Conci, Aura

    2016-07-01

    Breast cancer is the most common cancer among women worldwide. Diagnosis and treatment in early stages increase cure chances. The temperature of cancerous tissue is generally higher than that of healthy surrounding tissues, making thermography an option to be considered in screening strategies of this cancer type. This paper proposes a hybrid methodology for analyzing dynamic infrared thermography in order to indicate patients with risk of breast cancer, using unsupervised and supervised machine learning techniques, which characterizes the methodology as hybrid. The dynamic infrared thermography monitors or quantitatively measures temperature changes on the examined surface, after a thermal stress. In the dynamic infrared thermography execution, a sequence of breast thermograms is generated. In the proposed methodology, this sequence is processed and analyzed by several techniques. First, the region of the breasts is segmented and the thermograms of the sequence are registered. Then, temperature time series are built and the k-means algorithm is applied on these series using various values of k. Clustering formed by k-means algorithm, for each k value, is evaluated using clustering validation indices, generating values treated as features in the classification model construction step. A data mining tool was used to solve the combined algorithm selection and hyperparameter optimization (CASH) problem in classification tasks. Besides the classification algorithm recommended by the data mining tool, classifiers based on Bayesian networks, neural networks, decision rules and decision tree were executed on the data set used for evaluation. Test results support that the proposed analysis methodology is able to indicate patients with breast cancer. Among 39 tested classification algorithms, K-Star and Bayes Net presented 100% classification accuracy. Furthermore, among the Bayes Net, multi-layer perceptron, decision table and random forest classification algorithms, an

  6. Molecular diagnostics of lung cancer in the clinic.

    Science.gov (United States)

    Sholl, Lynette

    2017-10-01

    According to current practice guidelines, all patients with advanced non-small cell lung cancer (NSCLC) should undergo predictive biomarker testing. For squamous cell carcinoma patients, PD-L1 immunohistochemistry is indicated to select patients for immunotherapy in the first line. For lung adenocarcinoma, all patients with advanced disease should undergo testing for epidermal growth factor receptor ( EGFR ) mutations, ALK and ROS1 rearrangements, and PD-L1 expression to predict response to EGFR, ALK, or ROS1 targeted inhibitors or immunotherapy, respectively. Besides these, a number of other biomarkers are under clinical investigation as predictors of response to targeted therapies, including BRAF , ERBB2 , MET splice mutations and amplification, and RET rearrangements. Successful testing for this complex array of molecular targets demands careful coordination between proceduralists, pathologists and molecular laboratories to ensure proper tumor tissue handling following biopsy as well as judicious use of diagnostic immunohistochemistry. Even so, sample failure rates due to inadequate tumor tissue are high in practice, particularly when using sequential testing methods. Use of next generation sequencing (NGS) in clinical practice can enable detection of multiple targets and multiple alteration types (mutation, gene copy change, and rearrangement) simultaneously even with small amounts of input nucleic acids, thus increasing molecular testing success rates. In patients with an established lung cancer diagnosis but with prohibitively limited amounts of tumor tissue or who are experiencing relapse, analyses of circulating tumor DNA (ctDNA) from the plasma can serve as an alternate testing substrate, however the more limited clinical sensitivity of this approach must be taken into account. This review will explore the indications for and pitfalls of routine NGS and plasma genotyping in the clinic, including the intersection of these technologies.

  7. Basis for molecular diagnostics and immunotherapy for esophageal cancer.

    Science.gov (United States)

    Abdo, Joe; Agrawal, Devendra K; Mittal, Sumeet K

    2017-01-01

    Esophageal cancer (EC) is an extremely aggressive neoplasm, diagnosed in about 17,000 Americans every year with a mortality rate of more than 80% within five years and a median overall survival of just 13 months. For decades, the go-to regimen for esophageal cancer patients has been the use of taxane and platinum-based chemotherapy regimens, which has yielded the field's most dire survival statistics. Areas covered: Combination immunotherapy and a more robust molecular diagnostic platform for esophageal tumors could improve patient management strategies and potentially extend lives beyond the current survival figures. Analyzing a panel of biomarkers including those affiliated with taxane and platinum resistance (ERCC1 and TUBB3) as well as immunotherapy effectiveness (PD-L1) would provide oncologists more information on how to optimize first-line therapy for EC. Expert commentary: Of the 12 FDA-approved therapies in EC, zero target the genome. A majority of the approved drugs either target or are effected by proteomic expression. Therefore, a broader understanding of diagnostic biomarkers could give more clarity and direction in treating esophageal cancer in concert with a greater use of immunotherapy.

  8. Molecular signaling involving intrinsically disordered proteins in prostate cancer

    Directory of Open Access Journals (Sweden)

    Anna Russo

    2016-01-01

    Full Text Available Investigations on cellular protein interaction networks (PINs reveal that proteins that constitute hubs in a PIN are notably enriched in Intrinsically Disordered Proteins (IDPs compared to proteins that constitute edges, highlighting the role of IDPs in signaling pathways. Most IDPs rapidly undergo disorder-to-order transitions upon binding to their biological targets to perform their function. Conformational dynamics enables IDPs to be versatile and to interact with a broad range of interactors under normal physiological conditions where their expression is tightly modulated. IDPs are involved in many cellular processes such as cellular signaling, transcriptional regulation, and splicing; thus, their high-specificity/low-affinity interactions play crucial roles in many human diseases including cancer. Prostate cancer (PCa is one of the leading causes of cancer-related mortality in men worldwide. Therefore, identifying molecular mechanisms of the oncogenic signaling pathways that are involved in prostate carcinogenesis is crucial. In this review, we focus on the aspects of cellular pathways leading to PCa in which IDPs exert a primary role.

  9. Molecular medicine and the development of cancer chemopreventive agents.

    Science.gov (United States)

    Izzotti, Alberto

    2012-07-01

    Chemoprevention is effective in inhibiting the onset of cancer in experimental animal models, but the transferability of similar results to humans is questionable. Therefore, reliable intermediate molecular biomarkers are needed to evaluate the efficacy of chemopreventive agents before the onset of cancer. The use of genomic biomarkers is limited by their poor predictive value. Although post-genomic biomarkers (i.e., gene-expression analyses) are useful for evaluating the safety, efficacy, and mechanistic basis of chemopreventive agents, the biomarkers are often poorly related to the phenotype, due to posttranscriptional regulation. Proteome analyses can evaluate preclinical phenotype alterations, but only at low protein counts. MicroRNA alterations, which are essential for the development of cancer, may be modulated by chemopreventive agents. Furthermore, microRNA delivery may be used to counteract carcinogenesis. Exposure to cigarette smoke induces microRNA let-7 downregulation and cell proliferation that can be converted to cell growth arrest and apoptosis upon let-7a transfection. Therefore, microRNAs are reliable biomarkers for evaluating chemoprevention efficacy and may be used to counteract carcinogenesis. © 2012 New York Academy of Sciences.

  10. Molecular subtyping of cancer: current status and moving toward clinical applications.

    Science.gov (United States)

    Zhao, Lan; Lee, Victor H F; Ng, Michael K; Yan, Hong; Bijlsma, Maarten F

    2018-04-12

    Cancer is a collection of genetic diseases, with large phenotypic differences and genetic heterogeneity between different types of cancers and even within the same cancer type. Recent advances in genome-wide profiling provide an opportunity to investigate global molecular changes during the development and progression of cancer. Meanwhile, numerous statistical and machine learning algorithms have been designed for the processing and interpretation of high-throughput molecular data. Molecular subtyping studies have allowed the allocation of cancer into homogeneous groups that are considered to harbor similar molecular and clinical characteristics. Furthermore, this has helped researchers to identify both actionable targets for drug design as well as biomarkers for response prediction. In this review, we introduce five frequently applied techniques for generating molecular data, which are microarray, RNA sequencing, quantitative polymerase chain reaction, NanoString and tissue microarray. Commonly used molecular data for cancer subtyping and clinical applications are discussed. Next, we summarize a workflow for molecular subtyping of cancer, including data preprocessing, cluster analysis, supervised classification and subtype characterizations. Finally, we identify and describe four major challenges in the molecular subtyping of cancer that may preclude clinical implementation. We suggest that standardized methods should be established to help identify intrinsic subgroup signatures and build robust classifiers that pave the way toward stratified treatment of cancer patients.

  11. Molecular Pathology: A Requirement for Precision Medicine in Cancer.

    Science.gov (United States)

    Dietel, Manfred

    2016-01-01

    The increasing importance of targeting drugs and check-point inhibitors in the treatment of several tumor entities (breast, colon, lung, malignant melanoma, lymphoma, etc.) and the necessity of a companion diagnostic (HER2, (pan)RAS, EGFR, ALK, BRAF, ROS1, MET, PD-L1, etc.) is leading to new challenges for surgical pathology. Since almost all the biomarkers to be specifically detected are tissue based, a precise and reliable diagnostic is absolutely crucial. To meet this challenge surgical pathology has adapted a number of molecular methods (semi-quantitative immunohistochemistry, fluorescence in situ hybridization, PCR and its multiple variants, (pyro/Sanger) sequencing, next generation sequencing (amplicon, whole exome, whole genome), DNA arrays, methylation analyses, etc.) to be applicable for formalin-fixed paraffin-embedded tissue. Reading a patient's tissue as 'deeply' as possible and obtaining information on the morphological, genetic, proteomic and epigenetic background are the tasks of pathologists and molecular biologists and provide the clinicians with information relevant for precision medicine. Intensified cooperation between clinicians and pathologists will provide the basis of improved clinical drug selection and guide development of new cancer gene therapies and molecularly targeted drugs by research units and the pharmaceutical industry. © 2016 S. Karger GmbH, Freiburg.

  12. Online Series presents The Impact of Obesity on Cancer Risk | Division of Cancer Prevention

    Science.gov (United States)

    Obesity is a critical public health problem which is worsening over time. According to the Centers for Disease Control and Prevention, more than one third (34.9% or 78.6 million) of U.S. adults are obese. Growing obesity incidence is associated with detrimental health consequences including cancer. Experts in the field of nutrition and cancer will present the latest data and

  13. Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment

    Science.gov (United States)

    Willis, Rudolph E.

    2016-01-01

    It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis. PMID:27649156

  14. Analog series-based scaffolds: computational design and exploration of a new type of molecular scaffolds for medicinal chemistry

    Science.gov (United States)

    Dimova, Dilyana; Stumpfe, Dagmar; Hu, Ye; Bajorath, Jürgen

    2016-01-01

    Aim: Computational design of and systematic search for a new type of molecular scaffolds termed analog series-based scaffolds. Materials & methods: From currently available bioactive compounds, analog series were systematically extracted, key compounds identified and new scaffolds isolated from them. Results: Using our computational approach, more than 12,000 scaffolds were extracted from bioactive compounds. Conclusion: A new scaffold definition is introduced and a computational methodology developed to systematically identify such scaffolds, yielding a large freely available scaffold knowledge base. PMID:28116132

  15. Novel α, β-Unsaturated Sophoridinic Derivatives: Design, Synthesis, Molecular Docking and Anti-Cancer Activities

    Directory of Open Access Journals (Sweden)

    Yiming Xu

    2017-11-01

    Full Text Available Using sophoridine 1 and chalcone 3 as the lead compounds, a series of novel α, β-unsaturated sophoridinic derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity. Structure-activity relationship (SAR analysis indicated that introduction of α, β-unsaturated ketone moiety and heterocyclic group might significantly enhance anticancer activity. Among the compounds, 2f and 2m exhibited potential effects against HepG-2 and CNE-2 human cancer cell lines. Furthermore, molecular docking studies were performed to understand possible docking sites of the molecules on the target proteins and the mode of binding. This work provides a theoretical basis for structural optimizations and exploring anticancer pathways of this kind of compound.

  16. Synthesis, biological evaluation and molecular modeling of a novel series of 7-azaindole based tri-heterocyclic compounds as potent CDK2/Cyclin E inhibitors.

    Science.gov (United States)

    Baltus, Christine B; Jorda, Radek; Marot, Christophe; Berka, Karel; Bazgier, Václav; Kryštof, Vladimír; Prié, Gildas; Viaud-Massuard, Marie-Claude

    2016-01-27

    From four molecules, inspired by the structural features of fascaplysin, with an interesting potential to inhibit cyclin-dependent kinases (CDKs), we designed a new series of tri-heterocyclic derivatives based on 1H-pyrrolo[2,3-b]pyridine (7-azaindole) and triazole heterocycles. Using a Huisgen type [3 + 2] cycloaddition as the convergent key step, 24 derivatives were synthesized and their biological activities were evaluated. Comparative molecular field analysis (CoMFA), based on three-dimensional quantitative structure-activity relationship (3D-QSAR) studies, was conducted on a series of 30 compounds from the literature with high to low known inhibitory activity towards CDK2/cyclin E and was validated by a test set of 5 compounds giving satisfactory predictive r(2) value of 0.92. Remarkably, it also gave a good prediction of pIC50 for our tri-heterocyclic series which reinforce the validation of this model for the pIC50 prediction of external set compounds. The most promising compound, 43, showed a micro-molar range inhibitory activity against CDK2/cyclin E and also an antiproliferative and proapoptotic activity against a panel of cancer cell lines. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. Solitary thyroid metastasis from colon cancer: fine-needle aspiration cytology and molecular biology approach.

    Science.gov (United States)

    Onorati, M; Uboldi, P; Bianchi, C L; Nicola, M; Corradini, G M; Veronese, S; Fascì, A I; Di Nuovo, F

    2015-01-01

    Thyroid gland is one of the most vascularized organs of the body, nevertheless clinical and surgical series report an incidence of secondary malignancies in this gland of only 3%. Colorectal carcinoma metastatic to the thyroid gland is not as uncommon as previously believed, infact the number of cases seems to be increased in recent years due to the more frequent use of fine-needle aspiration cytology (FNAC) guided by ultrasonography. Although kidney, breast and lung metastases to the thyroid are frequent, metastasis from colon cancer is clinically rare with 52 cases reported in the literature in the last 5 decades and three cases described as solitary thyroid metastasis from the colon cancer without any other visceral metastases. To the best of our knowledge, we report the fourth case of solitary, asymptomatic thyroid metastasis from colon cancer without involvement of other organs. We discuss the importance of FNAC to detect metastatazing process as a compulsory step of the diagnostic and therapeutic management algorithm, combined with a molecular biology approach. A review of the last 5 decades literature, to update the number of cases described to date, is also included.

  18. Racial Disparities in the Molecular Landscape of Cancer.

    Science.gov (United States)

    Heath, Elisabeth I; Lynce, Filipa; Xiu, Joanne; Ellerbrock, Angela; Reddy, Sandeep K; Obeid, Elias; Liu, Stephen V; Bollig-Fischer, Aliccia; Separovic, Duska; Vanderwalde, Ari

    2018-04-01

    African Americans (AA) have the highest incidence and mortality of any racial/ethnic group in the US for most cancer types. Heterogeneity in the molecular biology of cancer, as a contributing factor to this disparity, is poorly understood. To address this gap in knowledge, we explored the molecular landscape of colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and high-grade glioma (HGG) from 271 AA and 636 Caucasian (CC) cases. DNA from formalin-fixed paraffin-embedded tumors was sequenced using next-generation sequencing. Additionally, we evaluated protein expression using immunohistochemistry. The Exome Aggregation Consortium Database was evaluated for known ethnicity associations. Considering only pathogenic or presumed pathogenic mutations, as determined by the American College of Medical Genetics and Genomics guidelines, and using Bonferroni and Benjamini-Hochberg corrections for multiple comparisons, we found that CRC tumors from AA patients harbored significantly more mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) than those from CC patients. CRC tumors in AA patients also appeared to harbor more mutations of mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1), MPL proto-oncogene (MPL), thrombo-poietin receptor, and neurofibromin 1 (NF1) than those from CC patients. In contrast, CRCs from AA patients were likely to carry fewer mutations of ataxia-telangiectasia mutated (ATM), as well as of proto-oncogene B-Raf (BRAF), including the V600E variant, than those from CC patients. Rates of immunohistochemical positivity for epidermal growth factor receptor (EGFR) and DNA topoisomerase 2-alpha (TOP2A) tended to be higher in CRCs from AA patients than in CC patients. In NSCLC adenocarcinoma, BRAF variants appeared to be more frequent in the AA than in the CC cohort, whereas in squamous cell lung carcinoma, programmed death-ligand 1 (PD-L1) expression tended to be lower in the AA than in CC group. Moreover

  19. Molecular markers in well-differentiated thyroid cancer.

    Science.gov (United States)

    D'Cruz, Anil K; Vaish, Richa; Vaidya, Abhishek; Nixon, Iain J; Williams, Michelle D; Vander Poorten, Vincent; López, Fernando; Angelos, Peter; Shaha, Ashok R; Khafif, Avi; Skalova, Alena; Rinaldo, Alessandra; Hunt, Jennifer L; Ferlito, Alfio

    2018-06-01

    Thyroid nodules are of common occurrence in the general population. About a fourth of these nodules are indeterminate on aspiration cytology placing many a patient at risk of unwanted surgery. The purpose of this review is to discuss various molecular markers described to date and place their role in proper perspective. This review covers the fundamental role of the signaling pathways and genetic changes involved in thyroid carcinogenesis. The current literature on the prognostic significance of these markers is also described. PubMed was used to search relevant articles. The key terms "thyroid nodules", "thyroid cancer papillary", "carcinoma papillary follicular", "carcinoma papillary", "adenocarcinoma follicular" were searched in MeSH, and "molecular markers", "molecular testing", mutation, BRAF, RAS, RET/PTC, PAX 8, miRNA, NIFTP in title and abstract fields. Multiple combinations were done and a group of experts in the subject from the International Head and Neck Scientific Group extracted the relevant articles and formulated the review. There has been considerable progress in the understanding of thyroid carcinogenesis and the emergence of numerous molecular markers in the recent years with potential to be used in the diagnostic algorithm of these nodules. However, their precise role in routine clinical practice continues to be a contentious issue. Majority of the studies in this context are retrospective and impact of these mutations is not independent of other prognostic factors making the interpretation difficult. The prevalence of these mutations in thyroid nodule is high and it is a continuously evolving field. Clinicians should stay informed as recommendation on the use of these markers is expected to evolve.

  20. Opportunities During Early Life for Cancer Prevention: Highlights From a Series of Virtual Meetings With Experts

    Science.gov (United States)

    Holman, Dawn M.; Buchanan, Natasha D.

    2018-01-01

    Compelling evidence suggests that early life exposures can affect lifetime cancer risk. In 2014, the Centers for Disease Control and Prevention’s (CDC’s) Cancer Prevention Across the Lifespan Workgroup hosted a series of virtual meetings with select experts to discuss the state of the evidence linking factors during the prenatal period and early childhood to subsequent risk of both pediatric and adult cancers. In this article, we present the results from a qualitative analysis of the meeting transcripts and summarize themes that emerged from our discussions with meeting participants. Themes included the state of the evidence linking early life factors to cancer risk, research gaps and challenges, the level of evidence needed to support taking public health action, and the challenges of communicating complex, and sometimes conflicting, scientific findings to the public. Opportunities for collaboration among public health agencies and other stakeholders were identified during these discussions. Potential next steps for the CDC and its partners included advancing and building upon epidemiology and surveillance work, developing and using evidence from multiple sources to inform decision-making, disseminating and communicating research findings in a clear and effective way, and expanding collaborations with grantees and other partners. As the science on early life factors and cancer risk continues to evolve, there are opportunities for collaboration to translate science into actionable public health practice. PMID:27940972

  1. Qigong program on insomnia and stress in cancer patients: A case series report

    Directory of Open Access Journals (Sweden)

    Seungmo Kim

    2015-01-01

    Full Text Available Background: In recent years, the interest in Qigong as an alternative therapy has grown following reports of its ability to regulate psychological factors in cancer patients. This is a case series to evaluate the outcome measures of Qigong when used as an adjunct to standard medical care to treat insomnia and stress in cancer patients. Patients and methods: The Qigong program was applied to four cancer patients with insomnia, stress, and anxiety. The program consisted of 30-min sessions involving exercise, patting of the 12 meridians, and spontaneous breathing exercises three times a week for a period of 4 weeks. The Pittsburgh Sleep Quality Index was measured as the primary outcome, while the Stress Scale, the State–Trait Anxiety Inventory, and the Functional Assessment Cancer Therapy–General determined the secondary outcomes. Insomnia, stress, and anxiety levels were examined weekly, while quality of life was examined on the first visit and the last visit. Results: The Pittsburgh Sleep Quality Index and Stress Scale scores were reduced after conduct of the Qigong program. Conclusion: This study could provide a better understanding of Qigong’s influence on insomnia and stress in cancer patients. However, a larger controlled trial should be conducted to confirm these findings.

  2. Gastric wall shortening in early gastric cancer: upper gastrointestinal series and pathologic correlation

    International Nuclear Information System (INIS)

    Kim, In Jae; Choi, Chul Soon; Kim, Eun Ah; Kim, Kyu Sun; Yun, Ku Sub; Kim, Ho Chul; Bae, Sang Hun; Kang, Gu; Shin, Hyung Sik

    1995-01-01

    To investigate the causes of gastric wall shortening in early gastric cancer, upper gastrointestinal study was correlated with pathologic findings. We evaluated 41 cases (M:F = 1.7:1, average age = 49) of early gastric cancer, retrospectively. The gastric wall shortening were classified as Grade I; none, Grade II; intermediate, and Grade III; prominent. Pathologic findings such as size of lesions, depth of tumor invasion, degree of the submucosal fibrosis, degree of thickness of the submucosa and muscularis propria, and morphologic patterns of lesions including conversing mucosal folds were correlated with the degree of gastric wall shortening on upper gastrointestinal series. Submucosal fibrosis was present in 4 cases in Grade I (n = 21), 4 cases in Grade II (n = 6) and 8 cases in Grade III (n = 10). Positive conversing mucosal folds were seen in 5 cases in Grade I (n = 17), 0 case in Grade II (n = 2) and 9 cases in Grade III (n = 9). Gastric wall shortening was significantly associated with submucosal fibrosis and conversing mucosal folds of early gastric cancer. (ρ = 0.0001, and ρ = 0.02, respectively) Upper gastrointestinal finding of gastric wall protrusion in patients with early gastric cancer should not misinterprete as advanced gastric cancer since the finding could be a result of submucosal fibrosis

  3. Molecular targets in cancer therapy: the Ron approach

    Directory of Open Access Journals (Sweden)

    Serena Germano

    2011-12-01

    Full Text Available The receptor tyrosine kinase Ron and its ligand, Macrophage Stimulating Protein (MSP, mediate multiple processes involved in the control of cell proliferation, migration and protection from apoptosis. Dysregulated signaling of Ron, due to hyperactivation or loss of negative regulation, is involved in tumor progression and metastasis. Growing evidence indicates that Ron is abnormally expressed and activated in certain types of primary epithelial cancers (i.e. breast, colon, lung, pancreas, bladder and thyroid, where it critically contributes to the maintenance of tumorigenic and invasive phenotype. Furthermore, a positive association between aberrant Ron expression and aggressive biological indicators as well as a worse clinical outcome have been reported in breast, bladder and thyroid carcinomas. Different approaches have proved effective in targeting receptor activation/expression both in vitro and in animal models, leading to reversion of the tumorigenic phenotype. Altogether these results show that Ron is an attractive molecular target for clinical intervention.

  4. Epidemiology and Molecular Biology of Head and Neck Cancer.

    Science.gov (United States)

    Jou, Adriana; Hess, Jochen

    2017-01-01

    Head and neck cancer is a common and aggressive malignancy with a high morbidity and mortality profile. Although the large majority of cases resemble head and neck squamous cell carcinoma (HNSCC), the current classification based on anatomic site and tumor stage fails to capture the high level of biologic heterogeneity, and appropriate clinical management remains a major challenge. Hence, a better understanding of the molecular biology of HNSCC is urgently needed to support biomarker development and personalized care for patients. This review focuses on recent findings based on integrative genomics analysis and multi-scale modeling approaches and how they are beginning to provide more sophisticated clues as to the biological and clinical diversity of HNSCC. © 2017 S. Karger GmbH, Freiburg.

  5. Challenges and opportunities in international molecular cancer prevention research: An ASPO Molecular Epidemiology and the Environment and International Cancer Prevention Interest Groups Report.

    Science.gov (United States)

    Epplein, Meira; Bostick, Roberd M; Mu, Lina; Ogino, Shuji; Braithwaite, Dejana; Kanetsky, Peter A

    2014-11-01

    The International Agency for Research on Cancer estimates that over half of the new cancer cases and almost two-thirds of the cancer deaths in 2012 occurred in low and middle income countries. To discuss the challenges and opportunities to reducing the burden of cancer worldwide, the Molecular Epidemiology and the Environment and the International Issues in Cancer Special Interest Groups joined forces to hold a session during the 38th Annual Meeting of the American Society of Preventive Oncology (March 2014, Arlington, Virginia). The session highlighted three topics of particular interest to molecular cancer prevention researchers working internationally, specifically: 1) biomarkers in cancer research; 2) environmental exposures and cancer; and 3) molecular pathological epidemiology. A major factor for successful collaboration illuminated during the discussion was the need for strong, committed, and reliable international partners. A key element of establishing such relationships is to thoroughly involve individual international collaborators in the development of the research question; engaged international collaborators are particularly motivated to champion and shepherd the project through all necessary steps, including issues relating to institutional review boards, political sensitivity, laboratory-based assays, and tumor subtyping. Also essential is allotting time for the building, maintaining, and investing in such relationships so that successful international collaborations may take root and bloom. While there are many challenges inherent to international molecular cancer research, the opportunities for furthering the science and prevention of cancer worldwide are great, particularly at this time of increasing cancer incidence and prevalence in low and middle income countries. ©2014 American Association for Cancer Research.

  6. Molecular Characterization and Mortality From Breast Cancer in Men.

    Science.gov (United States)

    Massarweh, Suleiman Alfred; Sledge, George W; Miller, Dave P; McCullough, Debbie; Petkov, Valentina I; Shak, Steven

    2018-05-10

    Purpose Limited data exist on the molecular biology, treatment, and outcomes of breast cancer in men, and much of our understanding in this area remains largely an extrapolation from data in women with breast cancer. Materials and Methods We studied men and women with hormone receptor-positive breast cancer and the 21-gene Breast Recurrence Score (RS) results. Differences in clinical characteristics and gene expression were determined, and distribution of RS results was correlated with 5-year breast cancer-specific survival (BCSS) and overall survival. Results There were 3,806 men and 571,115 women. Men were older than women (mean age, 64.2 v 59.1 years; P < .001). RS < 18 predominated in both genders, but RS ≥ 31 was more frequent in men (12.4% v 7.4%; P < .001), as were very low scores (RS < 11; 33.8% v 22.1%; P < .001). Mean gene expression was higher in men for the estrogen receptor (ER), proliferation, and invasion groups. ER was lowest and progesterone receptor was highest in women younger than 50 years of age, with a progressive increase in ER with age. Men younger than 50 years of age had slightly lower ER and progesterone receptor compared with older men. Survival data were available from SEER for 322 men and 55,842 women. Five-year BCSS was 99.0% (95% CI, 99.3% to 99.9%) and 95.9% (95% CI, 87.6% to 98.7%) for men with RS < 18 and RS 18-30, respectively, and for women, it was 99.5% (95% CI, 99.4% to 99.6%) and 98.6% (95% CI, 98.4% to 98.8%), respectively. RS ≥ 31 was associated with an 81.0% 5-year BCSS in men (95% CI, 53.3% to 93.2%) and 94.9% 5-year BCSS (95% CI, 93.9% to 95.7%) in women. Five-year BCSS and overall survival were lower in men than in women. Conclusion This study reveals some distinctive biologic features of breast cancer in men and an important prognostic role for RS testing in both men and women.

  7. Breast cancer molecular subtype classifier that incorporates MRI features.

    Science.gov (United States)

    Sutton, Elizabeth J; Dashevsky, Brittany Z; Oh, Jung Hun; Veeraraghavan, Harini; Apte, Aditya P; Thakur, Sunitha B; Morris, Elizabeth A; Deasy, Joseph O

    2016-07-01

    To use features extracted from magnetic resonance (MR) images and a machine-learning method to assist in differentiating breast cancer molecular subtypes. This retrospective Health Insurance Portability and Accountability Act (HIPAA)-compliant study received Institutional Review Board (IRB) approval. We identified 178 breast cancer patients between 2006-2011 with: 1) ERPR + (n = 95, 53.4%), ERPR-/HER2 + (n = 35, 19.6%), or triple negative (TN, n = 48, 27.0%) invasive ductal carcinoma (IDC), and 2) preoperative breast MRI at 1.5T or 3.0T. Shape, texture, and histogram-based features were extracted from each tumor contoured on pre- and three postcontrast MR images using in-house software. Clinical and pathologic features were also collected. Machine-learning-based (support vector machines) models were used to identify significant imaging features and to build models that predict IDC subtype. Leave-one-out cross-validation (LOOCV) was used to avoid model overfitting. Statistical significance was determined using the Kruskal-Wallis test. Each support vector machine fit in the LOOCV process generated a model with varying features. Eleven out of the top 20 ranked features were significantly different between IDC subtypes with P machine-learning-based predictive model using features extracted from MRI that can distinguish IDC subtypes with significant predictive power. J. Magn. Reson. Imaging 2016;44:122-129. © 2016 Wiley Periodicals, Inc.

  8. Epigenetic: a molecular link between testicular cancer and environmental exposures.

    Science.gov (United States)

    Vega, Aurelie; Baptissart, Marine; Caira, Françoise; Brugnon, Florence; Lobaccaro, Jean-Marc A; Volle, David H

    2012-01-01

    In the last decades, studies in rodents have highlighted links between in utero and/or neonatal exposures to molecules that alter endocrine functions and the development of genital tract abnormalities, such as cryptorchidism, hypospadias, and impaired spermatogenesis. Most of these molecules, called endocrine disrupters exert estrogenic and/or antiandrogenic activities. These data led to the hypothesis of the testicular dysgenesis syndrome which postulates that these disorders are one clinical entity and are linked by epidemiological and pathophysiological relations. Furthermore, infertility has been stated as a risk factor for testicular cancer (TC). The incidence of TC has been increasing over the past decade. Most of testicular germ cell cancers develop through a pre-invasive carcinoma in situ from fetal germ cells (primordial germ cell or gonocyte). During their development, fetal germ cells undergo epigenetic modifications. Interestingly, several lines of evidence have shown that gene regulation through epigenetic mechanisms (DNA and histone modifications) plays an important role in normal development as well as in various diseases, including TC. Here we will review chromatin modifications which can affect testicular physiology leading to the development of TC; and highlight potential molecular pathways involved in these alterations in the context of environmental exposures.

  9. [Molecular diagnostics of ALK-positive lung cancer].

    Science.gov (United States)

    Tímár, József; Lotz, Gábor; Rásó, Erzsébet; Moldvay, Judit

    2017-09-20

    ALK translocation is the 3rd most frequent genetic aberration in lung adenocarcinoma, and several inhibitors are now clinically available in first and second line settings. Accordingly, molecular diagnostics of ALK-positive lung cancer is very important and can be done with the rational combination of several methods. All international recommendations suggest that, except for cytological samples, screening technology for ALK-positive tumors is immunohistochemistry using a validated test. It is highly recommended that in case of ALK protein positive samples gene translocation must be confirmed by fluorescent in situ hybridization (FISH). In case of cytological samples FISH technique must be used as ALK diagnostics. In equivocal cases the genetic alteration of ALK can be confirmed by alternative molecular techniques such as next generation sequencing or RNAbased PCR methods. Upon administration of ALK inhibitors, acquired resistance is frequent which is mostly due to ALK amplification and/or mutation. It is evident that the diagnostics of these secondary ALK gene alterations must be done from recurrent tumors or circulating nucleic acids.

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

    OpenAIRE

    George H Sakorafas; Vasileios Smyrniotis

    2012-01-01

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

  11. Recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers

    DEFF Research Database (Denmark)

    Andersen, Lars Dyrskjøt; Zieger, Karsten; Ørntoft, Torben Falck

    2007-01-01

    individually contributed to the management of the disease. However, the development of high-throughput techniques for simultaneous assessment of a large number of markers has allowed classification of tumors into clinically relevant molecular subgroups beyond those possible by pathological classification. Here......Bladder cancer is the fifth most common neoplasm in industrialized countries. Due to frequent recurrences of the superficial form of this disease, bladder cancer ranks as one of the most common cancers. Despite the description of a large number of tumor markers for bladder cancers, none have......, we review the recent advances in high-throughput molecular marker identification for superficial and invasive bladder cancers....

  12. Molecular genetics of colorectal cancer Genética molecular del cáncer colorrectal

    Directory of Open Access Journals (Sweden)

    D. Cruz-Bustillo Clarens

    2004-01-01

    Full Text Available Colorectal tumours constitute an excellent system to study carcinogenesis and the molecular events implicated in the development of cancer. Attending to the way it is transmitted, colorectal cancer may appear in one of three forms: sporadic, familial, and hereditary. The sporadic form is most common and has no familial or hereditary associated factor thus far, while familial and hereditary forms show the same inheritance pattern. Hereditary colorectal cancers develop by means of defined stages that go from lesions in the crypt of the colon through adenomas to manifest cancer. They are characterised by the accumulation of multiple mutations in tumour suppressor genes and oncogenes that affect the balance between cell proliferation and apoptosis. The colorectal carcinogenesis pathway is not unique and there are probably several ways for the initiation, development and progression of colorectal tumours.Los tumores colorrectales constituyen un excelente sistema para estudiar la carcinogénesis y los eventos moleculares involucrados en el desarrollo de un tumor. El cáncer colorrectal puede presentarse en tres formas, según su forma de transmisión: esporádico, familiar y hereditario. La forma esporádica que es la mayoritaria, no tiene hasta el momento ningún factor familiar o hereditario asociado, mientras que las formas familiares y hereditarias siguen un patrón de herencia en la propensión familiar a padecerlo. Los cánceres colorrectales hereditarios se desarrollan mediante etapas definidas que van desde lesiones en la cripta del colon a través de adenomas hasta manifestar el cáncer y se caracterizan por la acumulación de múltiples mutaciones en genes supresores de tumor y oncogenes que afectan el balance entre la proliferación celular y la apoptosis. La vía de carcinogénesis colorrectal no es una sola y probablemente existan varios caminos para el inicio, desarrollo y progresión de un tumor colorrectal.

  13. Molecular markers in breast cancer: new tools in imaging and prognosis

    NARCIS (Netherlands)

    Vermeulen, J.F.

    2012-01-01

    Breast cancer is the most frequently diagnosed cancer in women. Although breast cancer is mainly diagnosed by mammography, other imaging modalities (e.g. MRI, PET) are increasingly used. The most recent developments in the field of molecular imaging comprise the application of near-infrared

  14. A novel series of conferences tackling the hurdles confronting the translation of novel cancer immunotherapies

    Directory of Open Access Journals (Sweden)

    Bot Adrian

    2012-11-01

    Full Text Available Abstract While there has been significant progress in advancing novel immune therapies to the bedside, much more needs to be done to fully tap into the potential of the immune system. It has become increasingly clear that besides practical and operational challenges, the heterogeneity of cancer and the limited efficacy profile of current immunotherapy platforms are the two main hurdles. Nevertheless, the promising clinical data of several approaches point to a roadmap that carries the promise to significantly advance cancer immunotherapy. A new annual series sponsored by Arrowhead Publishers and Conferences aims at bringing together scientific and business leadership from academia and industry, to identify, share and discuss most current priorities in research and translation of novel immune interventions. This Editorial provides highlights of the first event held earlier this year and outlines the focus of the second meeting to be held in 2013 that will be dedicated to stem cells and immunotherapy.

  15. A case series report of cancer patients undergoing group body psychotherapy [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Astrid Grossert

    2017-09-01

    Full Text Available Background: Disturbances in bodily wellbeing represent a key source of psychosocial suffering and impairment related to cancer. Therefore, interventions to improve bodily wellbeing in post-treatment cancer patients are of paramount importance. Notably, body psychotherapy (BPT has been shown to improve bodily wellbeing in subjects suffering from a variety of mental disorders. However, how post-treatment cancer patients perceive and subjectively react to group BPT aiming at improving bodily disturbances has, to the best of our knowledge, not yet been described. Methods: We report on six patients undergoing outpatient group BPT that followed oncological treatment for malignant neoplasms. The BPT consisted of six sessions based on a scientific embodiment approach, integrating body-oriented techniques to improve patients’ awareness, perception, acceptance, and expression regarding their body. Results: The BPT was well accepted by all patients. Despite having undergone different types of oncological treatment for different cancer types and locations, all subjects reported having appreciated BPT and improved how they perceived their bodies. However, individual descriptions of improvements showed substantial heterogeneity across subjects. Notably, most patients indicated that sensations, perceptions, and other mental activities related to their own body intensified when proceeding through the group BPT sessions. Conclusion: The findings from this case series encourage and inform future studies examining whether group BPT is efficacious in post-treatment cancer patients and investigating the related mechanisms of action. The observed heterogeneity in individual descriptions of perceived treatment effects point to the need for selecting comprehensive indicators of changes in disturbances of bodily wellbeing as the primary patient-reported outcome in future clinical trials. While increases in mental activities related to their own body are commonly

  16. UPAR targeted molecular imaging of cancers with small molecule-based probes.

    Science.gov (United States)

    Ding, Feng; Chen, Seng; Zhang, Wanshu; Tu, Yufeng; Sun, Yao

    2017-10-15

    Molecular imaging can allow the non-invasive characterization and measurement of biological and biochemical processes at the molecular and cellular levels in living subjects. The imaging of specific molecular targets that are associated with cancers could allow for the earlier diagnosis and better treatment of diseases. Small molecule-based probes play prominent roles in biomedical research and have high clinical translation ability. Here, with an emphasis on small molecule-based probes, we review some recent developments in biomarkers, imaging techniques and multimodal imaging in molecular imaging and highlight the successful applications for molecular imaging of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Detection of skeletal muscle metastases on initial staging of lung cancer: a retrospective case series.

    Science.gov (United States)

    Bocchino, Marialuisa; Valente, Tullio; Somma, Francesco; de Rosa, Ilaria; Bifulco, Marco; Rea, Gaetano

    2014-03-01

    Estimation of skeletal muscle metastases (SMMs) at the time of diagnosis and/or initial staging of lung cancer. Retrospective evaluation of clinical charts and imaging data suggestive of SMMs of patients with histology-proved lung cancer over a 5-year period. SMMs were identified in 46 out of 1,754 patients. Single and multiple (62.9% of cases) SMMs were detected by total body multi-detector computed tomography (MDCT). They were associated with poorly differentiated (43%) and advanced adenocarcinomas (52%) without clinically relevant symptoms and/or signs. Psoas and buttock muscles were most frequently involved (33.3%). MDCT findings consisted of well-defined homogeneously hyperdense oval masses (31%), lesions with ring-like enhancement and central hypoattenuation (68%), or large abscess-like necrotic lesions (24%). Sonography revealed well-defined hypoechoic masses (41.6%), ill-defined hypoechoic lesions (33.3%), or anechoic areas with a necrotic centre (25%). Positron emission tomography revealed that all SMMs were metabolically active. SMMs are uncommon but not negligible in lung cancer, with an estimated prevalence of 2.62% in our series. Although histology remains the recommended method, use of high-performance imaging techniques and increased clinical suspicion may improve their early detection. Efforts addressing their effect on the natural history of lung cancer are needed.

  18. Intracavitary irradiation of early rectal cancer for cure. A series of 186 cases

    International Nuclear Information System (INIS)

    Papillon, J.

    1975-01-01

    If radical surgery is the only rational policy for most cases of rectal cancer, the problem of local treatment in poor surgical risk patients should be discussed in selected cases. Only limited, fairly-well-differentiated tumors, still confined to the rectal wall may have a sufficiently low probability of lymphatic spread to be amenable to local treatment. Rectal cancer, usually regarded as being slightly radiosensitive when treated by external irradiation, proves to be highly radiosensitive in the case of early cancer treated by intracavitary irradiation. This method is able to control a large amount of limited polypoid and ulcerative adenocarcinomas. In a series of 133 cases followed more than 5 years, the rate of death from cancer is only 9 percent, and the 5-year survival rate is 78 percent. As compared with local excision or electrocoagulation, intracavitary irradiation has several advantages. It does not require colostomy nor anesthesia. Contact x-ray therapy is an ambulatory treatment applicable even to elderly and fragile patients. There is no danger of fistula in the case of tumor of the anterior wall in female patients. It preserves all the chances of cure by subsequent surgery in case of failure. (auth)

  19. Clinical Trials of Precision Medicine through Molecular Profiling: Focus on Breast Cancer.

    Science.gov (United States)

    Zardavas, Dimitrios; Piccart-Gebhart, Martine

    2015-01-01

    High-throughput technologies of molecular profiling in cancer, such as gene-expression profiling and next-generation sequencing, are expanding our knowledge of the molecular landscapes of several cancer types. This increasing knowledge coupled with the development of several molecularly targeted agents hold the promise for personalized cancer medicine to be fully realized. Moreover, an expanding armamentarium of targeted agents has been approved for the treatment of specific molecular cancer subgroups in different diagnoses. According to this paradigm, treatment selection should be dictated by the specific molecular aberrations found in each patient's tumor. The classical clinical trials paradigm of patients' eligibility being based on clinicopathologic parameters is being abandoned, with current clinical trials enrolling patients on the basis of specific molecular aberrations. New, innovative trial designs have been generated to better tackle the multiple challenges induced by the increasing molecular fragmentation of cancer, namely: (1) longitudinal cohort studies with or without downstream trials, (2) studies assessing the clinical utility of molecular profiling, (3) master or umbrella trials, (4) basket trials, (5) N-of-1 trials, and (6) adaptive design trials. This article provides an overview of the challenges for clinical trials in the era of molecular profiling of cancer. Subsequently, innovative trial designs with respective examples and their potential to expedite efficient clinical development of targeted anticancer agents is discussed.

  20. Pretreatment serum concentrations of 25-hydroxyvitamin D and breast cancer prognostic characteristics: a case-control and a case-series study.

    Directory of Open Access Journals (Sweden)

    Song Yao

    2011-02-01

    Full Text Available Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity.In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER, and molecular subtypes defined by ER, progesterone receptor (PR and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001. Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03. Levels were lowest among women with triple-negative cancer (17.5 ng/mL, significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002. In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08-0.53 than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22-0.56. The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses.In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant vitamin D supplementation for

  1. Pretreatment Serum Concentrations of 25-Hydroxyvitamin D and Breast Cancer Prognostic Characteristics: A Case-Control and a Case-Series Study

    Science.gov (United States)

    Yao, Song; Sucheston, Lara E.; Millen, Amy E.; Johnson, Candace S.; Trump, Donald L.; Nesline, Mary K.; Davis, Warren; Hong, Chi-Chen; McCann, Susan E.; Hwang, Helena; Kulkarni, Swati; Edge, Stephen B.; O'Connor, Tracey L.; Ambrosone, Christine B.

    2011-01-01

    Background Results from epidemiologic studies on the relationship between vitamin D and breast cancer risk are inconclusive. It is possible that vitamin D may be effective in reducing risk only of specific subtypes due to disease heterogeneity. Methods and Findings In case-control and case-series analyses, we examined serum concentrations of 25-hydroxyvitamin D (25OHD) in relation to breast cancer prognostic characteristics, including histologic grade, estrogen receptor (ER), and molecular subtypes defined by ER, progesterone receptor (PR) and HER2, among 579 women with incident breast cancer and 574 controls matched on age and time of blood draw enrolled in the Roswell Park Cancer Institute from 2003 to 2008. We found that breast cancer cases had significantly lower 25OHD concentrations than controls (adjusted mean, 22.8 versus 26.2 ng/mL, p<0.001). Among premenopausal women, 25OHD concentrations were lower in those with high- versus low-grade tumors, and ER negative versus ER positive tumors (p≤0.03). Levels were lowest among women with triple-negative cancer (17.5 ng/mL), significantly different from those with luminal A cancer (24.5 ng/mL, p = 0.002). In case-control analyses, premenopausal women with 25OHD concentrations above the median had significantly lower odds of having triple-negative cancer (OR = 0.21, 95% CI = 0.08–0.53) than those with levels below the median; and every 10 ng/mL increase in serum 25OHD concentrations was associated with a 64% lower odds of having triple-negative cancer (OR = 0.36, 95% CI = 0.22–0.56). The differential associations by tumor subtypes among premenopausal women were confirmed in case-series analyses. Conclusion In our analyses, higher serum levels of 25OHD were associated with reduced risk of breast cancer, with associations strongest for high grade, ER negative or triple negative cancers in premenopausal women. With further confirmation in large prospective studies, these findings could warrant

  2. Molecular biology of pancreatic cancer: how useful is it in clinical practice?

    Science.gov (United States)

    Sakorafas, George H; Smyrniotis, Vasileios

    2012-07-10

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

  3. 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.

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

    International Nuclear Information System (INIS)

    Abdollahi, H

    2014-01-01

    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

  5. The hallmarks of premalignant conditions: a molecular basis for cancer prevention.

    Science.gov (United States)

    Ryan, Bríd M; Faupel-Badger, Jessica M

    2016-02-01

    The hallmarks of premalignant lesions were first described in the 1970s, a time when relatively little was known about the molecular underpinnings of cancer. Yet it was clear there must be opportunities to intervene early in carcinogenesis. A vast array of molecular information has since been uncovered, with much of this stemming from studies of existing cancer or cancer models. Here, examples of how an understanding of cancer biology has informed cancer prevention studies are highlighted and emerging areas that may have implications for the field of cancer prevention research are described. A note of caution accompanies these examples, in that while there are similarities, there are also fundamental differences between the biology of premalignant lesions or premalignant conditions and invasive cancer. These differences must be kept in mind, and indeed leveraged, when exploring potential cancer prevention measures. Published by Elsevier Inc.

  6. Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatment, and Therapeutic Modalities

    Science.gov (United States)

    2011-02-01

    Therapeutic and Imaging Agents to Lung Cancer (PI and co-PI: Renata Pasqualini , Ph.D., Wadih Arap, M.D., Ph.D.) The studies outlined in this proposal...with Drs. Pasqualini , Arap, and Wistuba. The IHC staining of lung cancer TMAs (390 cases) has been completed. We are working with investigators to...Project 3, R. Pasqualini ). This project was completed and a manuscript is in preparation by Dr. Pasqualini’s lab. b) Molecular abnormalities

  7. Cancer of the Pancreas: Molecular Pathways and Current Advancement in Treatment.

    Science.gov (United States)

    Polireddy, Kishore; Chen, Qi

    2016-01-01

    Pancreatic cancer is one of the most lethal cancers among all malignances, with a median overall survival of cancers harbor a variety of genetic alternations that render it difficult to treat even with targeted therapy. Recent studies revealed that pancreatic cancers are highly enriched with a cancer stem cell (CSC) population, which is resistant to chemotherapeutic drugs, and therefore escapes chemotherapy and promotes tumor recurrence. Cancer cell epithelial to mesenchymal transition (EMT) is highly associated with metastasis, generation of CSCs, and treatment resistance in pancreatic cancer. Reviewed here are the molecular biology of pancreatic cancer, the major signaling pathways regulating pancreatic cancer EMT and CSCs, and the advancement in current clinical and experimental treatments for pancreatic cancer.

  8. Morphologic, Immunophenotypic, and Molecular Features of Epithelial Ovarian Cancer.

    Science.gov (United States)

    Ramalingam, Preetha

    2016-02-01

    Epithelial ovarian cancer comprises a heterogeneous group of tumors. The four most common subtypes are serous, endometrioid, clear cell, and mucinous carcinoma. Less common are transitional cell tumors, including transitional cell carcinoma and malignant Brenner tumor. While in the past these subtypes were grouped together and designated as epithelial ovarian tumors, these tumor types are now known to be separate entities with distinct clinical and biologic behaviors. From a therapeutic standpoint, current regimens employ standard chemotherapy based on stage and grade rather than histotype. However, this landscape may change in the era of personalized therapy, given that most subtypes (with the exception of high-grade serous carcinoma) are relatively resistant to chemotherapy. It is now well-accepted that high-grade and low-grade serous carcinomas represent distinct entities rather than a spectrum of the same tumor type. While they are similar in that patients present with advanced-stage disease, their histologic and molecular features are entirely different. High-grade serous carcinoma is associated with TP53 mutations, whereas low-grade serous carcinomas are associated with BRAF and KRAS mutations. Endometrioid and clear cell carcinomas typically present as early-stage disease and are frequently associated with endometriosis. Mucinous carcinomas typically present as large unilateral masses and often show areas of mucinous cystadenoma and mucinous borderline tumor. It must be emphasized that primary mucinous carcinomas are uncommon tumors, and metastasis from other sites such as the appendix, colon, stomach, and pancreaticobiliary tract must always be considered in the differential diagnosis. Lastly, transitional cell tumors of the ovary, specifically malignant Brenner tumors, are quite uncommon. High-grade serous carcinoma often has a transitional cell pattern, and adequate sampling in most cases shows more typical areas of serous carcinoma. Immunohistochemical

  9. Clinicopathologic and prognostic features of breast cancer in young women: a series from North of Morocco.

    Science.gov (United States)

    Bakkach, Joaira; Mansouri, Mohamed; Derkaoui, Touria; Loudiyi, Ali; Fihri, Mohamed; Hassani, Samia; Barakat, Amina; Ghailani Nourouti, Naima; Bennani Mechita, Mohcine

    2017-11-09

    Literature data reported a higher frequency of breast cancer in young women (BCYW) in developing countries. BCYW is associated with delayed diagnosis, aggressive biology and poor prognosis. However, our knowledge of biological profile, treatment received and outcome of young patients is still limited in Morocco. We propose to analyze clinicopathologic, therapeutic and prognostic features of BCYW among a series of patients native and/or inhabitant of North of Morocco. We carried out a retro-prospective study of 331 infiltrating breast cancer cases registered between January 2010 and December 2015. Details of tumor pathology, treatment and outcome were collected. Disease-Free Survival (DFS) and Overall Survival (OS) were assessed by Kaplan-Meier analysis. A total of 82 patients were diagnosed with breast cancer at the age of 40 or younger (24.8%). Median age was 36 years. More than one quarter (26%) of patients had family history of breast or ovarian cancer. Advanced stages accounted for 34.2% of cases. Median tumor diameter was 2.8 cm. Intermediate and high-grade tumors represented 47.6% and 40.2%, respectively. Nodal involvement was present in 58.5% and lymphovascular invasion was found in 47.7% of the patients. About two thirds (66.2%) of tumors were hormone receptor positive, 29.2% over-expressed HER2 receptor and 23% were triple negative. Patients underwent breast conserving surgery in 38.2% of cases, 61.7% were offered adjuvant chemotherapy and 84.6% received hormone therapy. Five-year DFS and OS were respectively 88.9% and 75.6%. Locoregional recurrence occurred in 2.8% of cases and 8.3% of patients developed distant metastases. Our findings are in accordance with previous studies that have shown a higher frequency of breast cancer among Moroccan young women. In line with literature data, clinicopathologic profile seems to be aggressive and prognosis is pejorative in our series.

  10. Molecular Mechanisms of Breast Cancer Metastasis and Potential Anti-metastatic Compounds.

    Science.gov (United States)

    Tungsukruthai, Sucharat; Petpiroon, Nalinrat; Chanvorachote, Pithi

    2018-05-01

    Throughout the world, breast cancer is among the major causes of cancer-related death and is the most common cancer found in women. The development of cancer molecular knowledge has surpassed the novel concept of cancer biology and unraveled principle targets for anticancer drug developments and treatment strategies. Metastatic breast cancer cells acquire their aggressive features through several mechanisms, including augmentation of survival, proliferation, tumorigenicity, and motility-related cellular pathways. Clearly, natural product-derived compounds have since long been recognized as an important source for anticancer drugs, several of which have been shown to have promising anti-metastasis activities by suppressing key molecular features supporting such cell aggressiveness. This review provides the essential details of breast cancer, the molecular-based insights into metastasis, as well as the effects and mechanisms of potential compounds for breast cancer therapeutic approaches. As the abilities of cancer cells to invade and metastasize are addressed as the hallmarks of cancer, compounds possessing anti-metastatic effects, together with their defined molecular drug action could benefit the development of new drugs as well as treatment strategies. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. Synthesis and Cytotoxic Evaluation of a Series of 2-Amino-Naphthoquinones against Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Thiago A. P. de Moraes

    2014-08-01

    Full Text Available The cytotoxicity of a series of aminonaphthoquinones resulting from the reaction of suitable aminoacids with 1,4-naphthoquinone was assayed against SF-295 (glioblastoma, MDAMB-435 (breast, HCT-8 (colon, HCT-116 (colon, HL-60 (leukemia, OVCAR-8 (ovarian, NCI-H358M (bronchoalveolar lung carcinoma and PC3-M (prostate cancer cells and also against PBMC (peripheral blood mononuclear cells. The results demonstrated that all the synthetic aminonaphthoquinones had relevant cytotoxic activity against all human cancer lines used in this experiment. Five of the compounds showed high cytotoxicity and selectivity against all cancer cell lines tested (IC50 = 0.49 to 3.89 µg·mL−1. The title compounds were less toxic to PBMC, since IC50 was 1.5 to eighteen times higher (IC50 = 5.51 to 17.61 µg·mL−1 than values shown by tumour cell lines. The mechanism of cell growth inhibition and structure–activity relationships remains as a target for future investigations.

  12. Clinical impact of extensive molecular profiling in advanced cancer patients

    Directory of Open Access Journals (Sweden)

    Sophie Cousin

    2017-02-01

    Full Text Available Abstract Previous precision medicine studies have investigated conventional molecular techniques and/or limited sets of gene alterations. The aim of this study was to describe the impact of the next-generation sequencing of the largest panel of genes used to date in tumour tissue and blood in the context of institutional molecular screening programmes. DNA analysis was performed by next-generation sequencing using a panel of 426 cancer-related genes and by comparative genomic hybridization from formalin-fixed and paraffin-embedded archived tumour samples when available or from fresh tumour samples. Five hundred sixty-eight patients were enrolled. The median number of prior lines of treatment was 2 (range 0–9. The most common primary tumour types were lung (16.9%, colorectal (14.4%, breast (10.6%, ovarian (10.2% and sarcoma (10.2%. The median patient age was 63 years (range 19–88. A total of 292 patients (51.4% presented with at least one actionable genetic alteration. The 20 genes most frequently altered were TP53, CDKN2A, KRAS, PTEN, PI3KCA, RB1, APC, ERBB2, MYC, EGFR, CDKN2B, ARID1A, SMAD4, FGFR1, MDM2, BRAF, ATM, CCNE1, FGFR3 and FRS2. One hundred fifty-nine patients (28% were included in early phase trials. The treatment was matched with a tumour profile in 86 cases (15%. The two main reasons for non-inclusion were non-progressive disease (31.5% and general status deterioration (25%. Twenty-eight percent of patients presented with a growth modulation index (time to progression under the early phase trial treatment/time to progression of the previous line of treatment >1.3. Extensive molecular profiling using high-throughput techniques allows for the identification of actionable mutations in the majority of cases and is associated with substantial clinical benefit in up to one in four patients.

  13. Altered molecular profile in thyroid cancers from patients affected by the Three Mile Island nuclear accident.

    Science.gov (United States)

    Goldenberg, David; Russo, Mariano; Houser, Kenneth; Crist, Henry; Derr, Jonathan B; Walter, Vonn; Warrick, Joshua I; Sheldon, Kathryn E; Broach, James; Bann, Darrin V

    2017-07-01

    In 1979, Three Mile Island (TMI) nuclear power plant experienced a partial meltdown with release of radioactive material. The effects of the accident on thyroid cancer (TC) in the surrounding population remain unclear. Radiation-induced TCs have a lower incidence of single nucleotide oncogenic driver mutations and higher incidence of gene fusions. We used next generation sequencing (NGS) to identify molecular signatures of radiation-induced TC in a cohort of TC patients residing near TMI during the time of the accident. Case series. We identified 44 patients who developed papillary thyroid carcinoma between 1974 and 2014. Patients who developed TC between 1984 and 1996 were at risk for radiation-induced TC, patients who developed TC before 1984 or after 1996 were the control group. We used targeted NGS of paired tumor and normal tissue from each patient to identify single nucleotide oncogenic driver mutations. Oncogenic gene fusions were identified using quantitative reverse transcription polymerase chain reaction. We identified 15 patients in the at-risk group and 29 patients in the control group. BRAF V600E mutations were identified in 53% patients in the at-risk group and 83% patients in the control group. The proportion of patients with BRAF mutations in the at-risk group was significantly lower than predicted by the The Cancer Genome Atlas cohort. Gene fusion or somatic copy number alteration drivers were identified in 33% tumors in the at-risk group and 14% of tumors in the control group. Findings were consistent with observations from other radiation-exposed populations. These data raise the possibility that radiation released from TMI may have altered the molecular profile of TC in the population surrounding TMI. 4 Laryngoscope, 127:S1-S9, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  14. Genomic analyses identify molecular subtypes of pancreatic cancer.

    Science.gov (United States)

    Bailey, Peter; Chang, David K; Nones, Katia; Johns, Amber L; Patch, Ann-Marie; Gingras, Marie-Claude; Miller, David K; Christ, Angelika N; Bruxner, Tim J C; Quinn, Michael C; Nourse, Craig; Murtaugh, L Charles; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourbakhsh, Ehsan; Wani, Shivangi; Fink, Lynn; Holmes, Oliver; Chin, Venessa; Anderson, Matthew J; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Xu, Qinying; Wilson, Peter J; Cloonan, Nicole; Kassahn, Karin S; Taylor, Darrin; Quek, Kelly; Robertson, Alan; Pantano, Lorena; Mincarelli, Laura; Sanchez, Luis N; Evers, Lisa; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chantrill, Lorraine A; Mawson, Amanda; Humphris, Jeremy; Chou, Angela; Pajic, Marina; Scarlett, Christopher J; Pinho, Andreia V; Giry-Laterriere, Marc; Rooman, Ilse; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Moran-Jones, Kim; Jamieson, Nigel B; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Grützmann, Robert; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Corbo, Vincenzo; Bassi, Claudio; Rusev, Borislav; Capelli, Paola; Salvia, Roberto; Tortora, Giampaolo; Mukhopadhyay, Debabrata; Petersen, Gloria M; Munzy, Donna M; Fisher, William E; Karim, Saadia A; Eshleman, James R; Hruban, Ralph H; Pilarsky, Christian; Morton, Jennifer P; Sansom, Owen J; Scarpa, Aldo; Musgrove, Elizabeth A; Bailey, Ulla-Maja Hagbo; Hofmann, Oliver; Sutherland, Robert L; Wheeler, David A; Gill, Anthony J; Gibbs, Richard A; Pearson, John V; Waddell, Nicola; Biankin, Andrew V; Grimmond, Sean M

    2016-03-03

    Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathological characteristics. Squamous tumours are enriched for TP53 and KDM6A mutations, upregulation of the TP63∆N transcriptional network, hypermethylation of pancreatic endodermal cell-fate determining genes and have a poor prognosis. Pancreatic progenitor tumours preferentially express genes involved in early pancreatic development (FOXA2/3, PDX1 and MNX1). ADEX tumours displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2 and RBPJL), and endocrine differentiation (NEUROD1 and NKX2-2). Immunogenic tumours contained upregulated immune networks including pathways involved in acquired immune suppression. These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development.

  15. Pathological Bases for a Robust Application of Cancer Molecular Classification

    Directory of Open Access Journals (Sweden)

    Salvador J. Diaz-Cano

    2015-04-01

    Full Text Available Any robust classification system depends on its purpose and must refer to accepted standards, its strength relying on predictive values and a careful consideration of known factors that can affect its reliability. In this context, a molecular classification of human cancer must refer to the current gold standard (histological classification and try to improve it with key prognosticators for metastatic potential, staging and grading. Although organ-specific examples have been published based on proteomics, transcriptomics and genomics evaluations, the most popular approach uses gene expression analysis as a direct correlate of cellular differentiation, which represents the key feature of the histological classification. RNA is a labile molecule that varies significantly according with the preservation protocol, its transcription reflect the adaptation of the tumor cells to the microenvironment, it can be passed through mechanisms of intercellular transference of genetic information (exosomes, and it is exposed to epigenetic modifications. More robust classifications should be based on stable molecules, at the genetic level represented by DNA to improve reliability, and its analysis must deal with the concept of intratumoral heterogeneity, which is at the origin of tumor progression and is the byproduct of the selection process during the clonal expansion and progression of neoplasms. The simultaneous analysis of multiple DNA targets and next generation sequencing offer the best practical approach for an analytical genomic classification of tumors.

  16. Molecular basis of colorectal cancer: Towards an individualized management?

    Directory of Open Access Journals (Sweden)

    J. Perea

    Full Text Available Colorectal cancer (CRC has become a highly relevant condition nowadays. In this respect, advances in the understanding of its molecular basis are key for an adequate management. From the time when the adenoma-carcinoma sequence was formulated as a carcinogenesis model to this day, when, among other things, three major carcinogenic pathways have been identified, the CRC concept has evolved from that of a single disease to the notion that each CRC is a differentiated condition in itself. The suppressor or chromosome instability pathway, the mutator or microsatellite instability pathway, and the methylator or CpG island methylation pathway allow various phenotypes to be identified within CRC. Similarly, the presence of different changes in certain genes confers several behaviors on CRC from both the prognostic and responsive standpoints to specific therapies. However, this apparent complexity does help develop the clinical management of this disease through the identification of novel, more specific therapy targets, and also markers for various behaviors within the condition, which will most likely lead us to an individualized management for these patients.

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

    Science.gov (United States)

    Dillon, Christopher P; Green, Douglas R

    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.

  18. A Linked Series of Laboratory Exercises in Molecular Biology Utilizing Bioinformatics and GFP

    Science.gov (United States)

    Medin, Carey L.; Nolin, Katie L.

    2011-01-01

    Molecular biologists commonly use bioinformatics to map and analyze DNA and protein sequences and to align different DNA and protein sequences for comparison. Additionally, biologists can create and view 3D models of protein structures to further understand intramolecular interactions. The primary goal of this 10-week laboratory was to introduce…

  19. 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

  20. Multiclass classification for skin cancer profiling based on the integration of heterogeneous gene expression series.

    Science.gov (United States)

    Gálvez, Juan Manuel; Castillo, Daniel; Herrera, Luis Javier; San Román, Belén; Valenzuela, Olga; Ortuño, Francisco Manuel; Rojas, Ignacio

    2018-01-01

    Most of the research studies developed applying microarray technology to the characterization of different pathological states of any disease may fail in reaching statistically significant results. This is largely due to the small repertoire of analysed samples, and to the limitation in the number of states or pathologies usually addressed. Moreover, the influence of potential deviations on the gene expression quantification is usually disregarded. In spite of the continuous changes in omic sciences, reflected for instance in the emergence of new Next-Generation Sequencing-related technologies, the existing availability of a vast amount of gene expression microarray datasets should be properly exploited. Therefore, this work proposes a novel methodological approach involving the integration of several heterogeneous skin cancer series, and a later multiclass classifier design. This approach is thus a way to provide the clinicians with an intelligent diagnosis support tool based on the use of a robust set of selected biomarkers, which simultaneously distinguishes among different cancer-related skin states. To achieve this, a multi-platform combination of microarray datasets from Affymetrix and Illumina manufacturers was carried out. This integration is expected to strengthen the statistical robustness of the study as well as the finding of highly-reliable skin cancer biomarkers. Specifically, the designed operation pipeline has allowed the identification of a small subset of 17 differentially expressed genes (DEGs) from which to distinguish among 7 involved skin states. These genes were obtained from the assessment of a number of potential batch effects on the gene expression data. The biological interpretation of these genes was inspected in the specific literature to understand their underlying information in relation to skin cancer. Finally, in order to assess their possible effectiveness in cancer diagnosis, a cross-validation Support Vector Machines (SVM

  1. Molecular identification of vectors of Leishmania in Colombia: mitochondrial introgression in the Lutzomyia townsendi series.

    Science.gov (United States)

    Testa, J M; Montoya-Lerma, J; Cadena, H; Oviedo, M; Ready, P D

    2002-12-01

    The identity of the sandfly vectors of Leishmania braziliensis in Valle del Cauca Department, Colombia, was originally given as Lutzomyia townsendi, but then changed to L. youngi, another member of the L. townsendi series (Verrucarum group) with isomorphic females. To identify members of this series in Valle del Cauca, we analyzed the nuclear gene elongation factor-alpha (EF-alpha) and the mitochondrial gene cytochrome b (Cyt b). DNA sequences from the L. verrucarum series (L. columbiana, L. evansi and L. ovallesi) were used as outgroups. Flies from two locations on the western cordillera of the Andes were identified as L. townsendi s.s., according to male morphology and distinctive gene lineages. In the third location, on the central cordillera of the Andes, most specimens were identified as belonging to a geographical population of L. youngi, according to male morphology, an EF-alpha lineage shared with L. youngi from the Venezuelan-type locality, and a distinctive Cyt b sub-lineage. All other specimens were identified as L. youngi with the introgressed Cyt b sequences of L. townsendi. Such interspecific introgression implies that vectorial traits and ecological associations may no longer be viewed as fixed properties of different morphospecies.

  2. Development and validation of risk models and molecular diagnostics to permit personalized management of cancer.

    Science.gov (United States)

    Pu, Xia; Ye, Yuanqing; Wu, Xifeng

    2014-01-01

    Despite the advances made in cancer management over the past few decades, improvements in cancer diagnosis and prognosis are still poor, highlighting the need for individualized strategies. Toward this goal, risk prediction models and molecular diagnostic tools have been developed, tailoring each step of risk assessment from diagnosis to treatment and clinical outcomes based on the individual's clinical, epidemiological, and molecular profiles. These approaches hold increasing promise for delivering a new paradigm to maximize the efficiency of cancer surveillance and efficacy of treatment. However, they require stringent study design, methodology development, comprehensive assessment of biomarkers and risk factors, and extensive validation to ensure their overall usefulness for clinical translation. In the current study, the authors conducted a systematic review using breast cancer as an example and provide general guidelines for risk prediction models and molecular diagnostic tools, including development, assessment, and validation. © 2013 American Cancer Society.

  3. Application of Deep Learning in Automated Analysis of Molecular Images in Cancer: A Survey

    Science.gov (United States)

    Xue, Yong; Chen, Shihui; Liu, Yong

    2017-01-01

    Molecular imaging enables the visualization and quantitative analysis of the alterations of biological procedures at molecular and/or cellular level, which is of great significance for early detection of cancer. In recent years, deep leaning has been widely used in medical imaging analysis, as it overcomes the limitations of visual assessment and traditional machine learning techniques by extracting hierarchical features with powerful representation capability. Research on cancer molecular images using deep learning techniques is also increasing dynamically. Hence, in this paper, we review the applications of deep learning in molecular imaging in terms of tumor lesion segmentation, tumor classification, and survival prediction. We also outline some future directions in which researchers may develop more powerful deep learning models for better performance in the applications in cancer molecular imaging. PMID:29114182

  4. Molecular Characterization of H.pylori Strains and Biomarkers in Gastric Cancer

    Science.gov (United States)

    2017-07-01

    AWARD NUMBER: W81XWH-16-1-0274 TITLE: Molecular Characterization of H.pylori Strains and Biomarkers in Gastric Cancer PRINCIPAL INVESTIGATOR...SUBTITLE Molecular Characterization of H.pylori Strains and Biomarkers in Gastric Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0274 5c...organoid technology via collaboration with Dr. Mary Estes (Baylor College of Medicine ) and her lab, via one-on-one visits, has guided Dr. Alex Peniche with

  5. Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study

    Directory of Open Access Journals (Sweden)

    Reuveni T

    2011-11-01

    Full Text Available Tobi Reuveni1, Menachem Motiei1, Zimam Romman2, Aron Popovtzer3, Rachela Popovtzer11Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-ilan University, Ramat Gan, 2GE HealthCare, Tirat Hacarmel, 3Department of Otorhinolaryngology, Head and Neck Surgery and Onology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, IsraelAbstract: In recent years, advances in molecular biology and cancer research have led to the identification of sensitive and specific biomarkers that associate with various types of cancer. However, in vivo cancer detection methods with computed tomography, based on tracing and detection of these molecular cancer markers, are unavailable today. This paper demonstrates in vivo the feasibility of cancer diagnosis based on molecular markers rather than on anatomical structures, using clinical computed tomography. Anti-epidermal growth factor receptor conjugated gold nanoparticles (30 nm were intravenously injected into nude mice implanted with human squamous cell carcinoma head and neck cancer. The results clearly demonstrate that a small tumor, which is currently undetectable through anatomical computed tomography, is enhanced and becomes clearly visible by the molecularly-targeted gold nanoparticles. It is further shown that active tumor targeting is more efficient and specific than passive targeting. This noninvasive and nonionizing molecular cancer imaging tool can facilitate early cancer detection and can provide researchers with a new technique to investigate in vivo the expression and activity of cancer-related biomarkers and molecular processes.Keywords: functional computed tomography, molecular imaging, gold nanoparticles, biologically targeted in vivo imaging, contrast agents

  6. 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.

  7. What Bacteria Are Living in My Food?: An Open-Ended Practical Series Involving Identification of Unknown Foodborne Bacteria Using Molecular Techniques

    Science.gov (United States)

    Prasad, Prascilla; Turner, Mark S.

    2011-01-01

    This open-ended practical series titled "Molecular Identification of Unknown Food Bacteria" which extended over a 6-week period was designed with the aims of giving students an opportunity to gain an understanding of naturally occurring food bacteria and skills in contemporary molecular methods using real food samples. The students first isolated…

  8. 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

  9. Molecular biomarker set for early detection of ovarian cancer

    KAUST Repository

    Bajic, Vladimir B.

    2015-06-16

    Embodiments of the present invention concern methods and compositions related to detection of ovarian cancer, including detection of the stage of ovarian cancer, in some cases. In particular, the invention encompasses use of expression of TFAP2A and in some embodiments CA125 and/or E2F5 to identify ovarian cancer, including detecting mRNA and/or protein levels of the respective gene products. Kits for detection of ovarian cancer are also described.

  10. Molecular biomarker set for early detection of ovarian cancer

    KAUST Repository

    Bajic, Vladimir B.; Kaur, Mandeep

    2015-01-01

    Embodiments of the present invention concern methods and compositions related to detection of ovarian cancer, including detection of the stage of ovarian cancer, in some cases. In particular, the invention encompasses use of expression of TFAP2A and in some embodiments CA125 and/or E2F5 to identify ovarian cancer, including detecting mRNA and/or protein levels of the respective gene products. Kits for detection of ovarian cancer are also described.

  11. Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?

    Science.gov (United States)

    Jácome, Alexandre Andrade Dos Anjos; Lima, Enaldo Melo de; Kazzi, Ana Izabela; Chaves, Gabriela Freitas; Mendonça, Diego Cavalheiro de; Maciel, Marina Mara; Santos, José Sebastião Dos

    2016-04-01

    Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.

  12. Sputum-Based Molecular Biomarkers for the Early Detection of Lung Cancer: Limitations and Promise

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Connie E. [Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine. 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Tchou-Wong, Kam-Meng; Rom, William N., E-mail: william.rom@nyumc.org [Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine. 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

    2011-07-19

    Lung cancer is the leading cause of cancer deaths, with an overall survival of 15% at five years. Biomarkers that can sensitively and specifically detect lung cancer at early stage are crucial for improving this poor survival rate. Sputum has been the target for the discovery of non-invasive biomarkers for lung cancer because it contains airway epithelial cells, and molecular alterations identified in sputum are most likely to reflect tumor-associated changes or field cancerization caused by smoking in the lung. Sputum-based molecular biomarkers include morphology, allelic imbalance, promoter hypermethylation, gene mutations and, recently, differential miRNA expression. To improve the sensitivity and reproducibility of sputum-based biomarkers, we recommend standardization of processing protocols, bronchial epithelial cell enrichment, and identification of field cancerization biomarkers.

  13. Dissecting the roles of the androgen receptor in prostate cancer from molecular perspectives.

    Science.gov (United States)

    Hu, Jieping; Wang, Gongxian; Sun, Ting

    2017-05-01

    Androgen receptor plays a pivotal role in prostate cancer progression, and androgen deprivation therapy to intercept androgen receptor signal pathway is an indispensable treatment for most advanced prostate cancer patients to delay cancer progression. However, the emerging of castration-resistant prostate cancer reminds us the alteration of androgen receptor, which includes androgen receptor mutation, the formation of androgen receptor variants, and androgen receptor distribution in cancer cells. In this review, we introduce the process of androgen receptor and also its variants' formation, translocation, and function alteration by protein modification or interaction with other pathways. We dissect the roles of androgen receptor in prostate cancer from molecular perspective to provide clues for battling prostate cancer, especially castration-resistant prostate cancer.

  14. Gastric tumours in hereditary cancer syndromes: clinical features, molecular biology and strategies for prevention.

    Science.gov (United States)

    Sereno, María; Aguayo, Cristina; Guillén Ponce, Carmen; Gómez-Raposo, César; Zambrana, Francisco; Gómez-López, Miriam; Casado, Enrique

    2011-09-01

    Gastric cancer is the major cause of cancer-related deaths worldwide. The majority of them are classified as sporadic, whereas the remaining 10% exhibit familial clustering. Hereditary diffuse gastric cancer (HDGC) syndrome is the most important condition that leads to hereditary gastric cancer. However, other hereditary cancer syndromes, such as hereditary non-polyposis colorectal cancer, familial adenomatous polyposis, Peutz-Jeghers syndrome, Li-Fraumeni syndrome and hereditary breast and ovarian cancer, entail a higher risk compared to the general population for developing this kind of neoplasia. In this review, we describe briefly the most important aspects related to clinical features, molecular biology and strategies for prevention in hereditary gastric associated to different cancer syndromes.

  15. Molecular prognostic markers in ovarian cancer : toward patient-tailored therapy

    NARCIS (Netherlands)

    Crijns, APG; Duiker, EW; de Jong, S; Willemse, PHB; van der Zee, AGJ; de Vries, EGE

    2006-01-01

    In ovarian cancer the ceiling seems to be reached with chemotherapeutic drugs. Therefore a paradigm shift is needed. Instead of treating all patients according to standard guidelines, individualized molecular targeted treatment should be aimed for. This means that molecular profiles of the distinct

  16. Interaction of pathology and molecular characterization of thyroid cancers

    International Nuclear Information System (INIS)

    Williams, E.D.; Cherstvoy, E.; Egloff, B.; Hoefler, H.; Vecchio, G.; Bogdanova, T.; Bragarnik, M.; Tronko, N.D.

    1996-01-01

    This paper presents the results of joint studies of thyroid cancer in children under 15 years of age between departments in Cambridge, Brussels, Naples and Munich in the European Union, and departments in Minsk, Kiev and Obninsk in the newly independent states of Eastern Europe. The pathology of 264 cases of childhood thyroid cancer out of 430 that have occurred since 1990 in the 3 countries in which high levels of fallout from the Chernobyl accident occurred has been restudied by NIS and EU pathologists. The overall level of agreement reached was about 97%. The diagnosis was supported by immunocytochemistry and ISH for the differentiation markers, thyroglobulin and calcitonin, and the tumors were classified according to the WHO, with papillary carcinomas being further subclassified. 99% of the 134 Belarussian cases were papillary carcinomas, as were 94% of the 114 Ukrainian tumors. All 9 of the Russian cases available for study were papillary in type. 76 of 154 cases of childhood thyroid cancer reviewed over a 30 year period in England and Wales and were also studied, 68% of these were papillary carcinoma. Histological study showed that a subtype of papillary carcinoma, rarely found in adults, with a solid/follicular architecture occurred in children. It was found in 72% of the Belarussian papillary carcinomas, 76% of the Ukrainian cases, but only 40% of the England and Wales cases. Molecular biological studies showed that the proportion of cases of papillary carcinoma expressing the ret gene was not significantly different in the exposed and the unexposed tumors, studies of the type of translocation leading to ret gene expression are not yet conclusive. Ras gene mutations were found as expected in follicular carcinoma, but were absent from any papillary carcinoma, whether from exposed or unexposed cases. TSH receptor mutations, normally found in follicular tumors were not found in any papillary carcinomas, nor were any p53 mutations identified. All these results

  17. The Association Between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer Risk

    Science.gov (United States)

    2017-08-01

    AWARD NUMBER: W81XWH-15-1-0273 TITLE: The Association between Molecular Markers in Colorectal Sessile Serrated Polyps and Colorectal Cancer ... Colorectal Cancer Risk 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-15-1-0273 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Andrea Burnett-Hartman 5d... cancer in patients with sessile serrated colorectal polyps (SSPs). The project’s specific aims are as follows: 1) Estimate the risk of colorectal

  18. 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.

  19. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...... staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined...

  20. Molecular and genetic epidemiology of cancer in low- and medium-income countries.

    Science.gov (United States)

    Malhotra, Jyoti

    2014-01-01

    Genetic and molecular factors can play an important role in an individual's cancer susceptibility and response to carcinogen exposure. Cancer susceptibility and response to carcinogen exposure can be either through inheritance of high penetrance but rare germline mutations that constitute heritable cancer syndromes, or it can be inherited as common genetic variations or polymorphisms that are associated with low to moderate risk for development of cancer. These polymorphisms can interact with environmental exposures and can influence an individual's cancer risk through multiple pathways, including affecting the rate of metabolism of carcinogens or the immune response to these toxins. Thus, these genetic polymorphisms can account for some of the geographical differences seen in cancer prevalence between different populations. This review explores the role of molecular epidemiology in the field of cancer prevention and control in low- and medium-income countries. Using data from Human Genome Project and HapMap Project, genome-wide association studies have been able to identify multiple susceptibility loci for different cancers. The field of genetic and molecular epidemiology has been further revolutionized by the discovery of newer, faster, and more efficient DNA-sequencing technologies including next-generation sequencing. The new DNA-sequencing technologies can play an important role in planning and implementation of cancer prevention and screening strategies. More research is needed in this area, especially in investigating new biomarkers and measuring gene-environment interactions. Copyright © 2014 Icahn School of Medicine at Mount Sinai. Published by Elsevier Inc. All rights reserved.

  1. The market trend analysis and prospects of cancer molecular diagnostics kits.

    Science.gov (United States)

    Seo, Ju Hwan; Lee, Joon Woo; Cho, Daemyeong

    2018-01-01

    The molecular diagnostics market can be broadly divided into PCR (rt-PCR, d-PCR), NGS(Next Generation Sequencing), Microarray, FISH(Fluorescent in situ-hybridization) and other categories, based on the diagnostic technique. Also, depending on the disease being diagnosed, the market can also be divided into cancer, infectious diseases, HIV/STDs (herpes, syphilis), and women's health issues such as breast cancer, cervical cancer, ovarian cancer, HPV(human papillomavirus), and vaginitis.Chromosome analysis (including Fluorescent In-situ Hybridization) is one type of blood cancer diagnostic method, which involves the direct detection of individual cells with chromosomal translocation, but there have been problems of sensitivity when using this method. PCR targeting individual genes or the RT (reverse transcription)-PCR method offers outstanding sensitivity, but one drawback is the risk of false-positive reaction caused by contamination of samples, etc. Blood cancer molecular diagnostics kits allow us to overcome these shortcomings, and related products have been under development, with a focus on improving detection sensitivity, enabling multiple tests, and reducing the cost and diagnostic time. Blood cancer molecular diagnostics is usually performed based on platforms such as PCR. The global market for blood cancer molecular diagnostics kits is $ 335.9 million as of 2016 and is expected to reach $ 6980 million in 2026 with an average annual growth rate of 32.9%. The market in South Korea is anticipated to grow at an average annual rate of 28.9%, from $ 3.75 million as of 2016 to $ 60.89 million in 2026. The Market for blood cancer molecular diagnostics kits is judged to be higher in growth possibility due to the increase in the number of cancer patients.

  2. Molecular lipidomics of exosomes released by PC-3 prostate cancer cells

    DEFF Research Database (Denmark)

    Llorente, A.; Skotland, T.; Sylvanne, T.

    2013-01-01

    The molecular lipid composition of exosomes is largely unknown. In this study, sophisticated shotgun and targeted molecular lipidomic assays were performed for in-depth analysis of the lipidomes of the metastatic prostate cancer cell line, PC-3, and their released exosomes. This study, based...... in the quantification of approximately 280 molecular lipid species, provides the most extensive lipid analysis of cells and exosomes to date. Interestingly, major differences were found in the lipid composition of exosomes compared to parent cells. Exosomes show a remarkable enrichment of distinct lipids, demonstrating...... potentially be used as cancer biomarkers. (C) 2013 Elsevier B.V. All rights reserved....

  3. Advances in the Molecular Analysis of Breast Cancer: Pathway Toward Personalized Medicine.

    Science.gov (United States)

    Rosa, Marilin

    2015-04-01

    Breast cancer is a heterogeneous disease that encompasses a wide range of clinical behaviors and histological and molecular variants. It is the most common type of cancer affecting women worldwide and is the second leading cause of cancer death. A comprehensive literature search was performed to explore the advances in molecular medicine related to the diagnosis and treatment of breast cancer. During the last few decades, advances in molecular medicine have changed the landscape of cancer treatment as new molecular tests complement and, in many instances, exceed traditional methods for determining patient prognosis and response to treatment options. Personalized medicine is becoming the standard of care around the world. Developments in molecular profiling, genomic analysis, and the discovery of targeted drug therapies have significantly improved patient survival rates and quality of life. This review highlights what pathologists need to know about current molecular tests for classification and prognostic/ predictive assessment of breast carcinoma as well as their role as part of the medical team.

  4. Unique molecular landscapes in cancer: implications for individualized, curated drug combinations.

    Science.gov (United States)

    Wheler, Jennifer; Lee, J Jack; Kurzrock, Razelle

    2014-12-15

    With increasingly sophisticated technologies in molecular biology and "omic" platforms to analyze patients' tumors, more molecular diversity and complexity in cancer are being observed. Recently, we noted unique genomic profiles in a group of patients with metastatic breast cancer based on an analysis with next-generation sequencing. Among 57 consecutive patients, no two had the same molecular portfolio. Applied genomics therefore appears to represent a disruptive innovation in that it unveils a heterogeneity to metastatic cancer that may be ill-suited to canonical clinical trials and practice paradigms. Upon recognizing that patients have unique tumor landscapes, it is possible that there may be a "mismatch" between our traditional clinical trials system that selects patients based on common characteristics to evaluate a drug (drug-centric approach) and optimal treatment based on curated, individualized drug combinations for each patient (patient-centric approach). ©2014 American Association for Cancer Research.

  5. Molecular MR imaging of cancer gene therapy. Ferritin transgene reporter takes the stage

    International Nuclear Information System (INIS)

    Hasegawa, Sumitaka; Furukawa, Takako; Saga, Tsuneo

    2010-01-01

    Molecular imaging using magnetic resonance (MR) imaging has been actively investigated and made rapid progress in the past decade. Applied to cancer gene therapy, the technique's high spatial resolution allows evaluation of gene delivery into target tissues. Because noninvasive monitoring of the duration, location, and magnitude of transgene expression in tumor tissues or cells provides useful information for assessing therapeutic efficacy and optimizing protocols, molecular imaging is expected to become a critical step in the success of cancer gene therapy in the near future. We present a brief overview of the current status of molecular MR imaging, especially in vivo reporter gene imaging using ferritin and other reporters, discuss its application to cancer gene therapy, and present our research of MR imaging detection of electroporation-mediated cancer gene therapy using the ferritin reporter gene. (author)

  6. [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.

  7. Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics.

    Science.gov (United States)

    Hirsch, B; Endris, V; Lassmann, S; Weichert, W; Pfarr, N; Schirmacher, P; Kovaleva, V; Werner, M; Bonzheim, I; Fend, F; Sperveslage, J; Kaulich, K; Zacher, A; Reifenberger, G; Köhrer, K; Stepanow, S; Lerke, S; Mayr, T; Aust, D E; Baretton, G; Weidner, S; Jung, A; Kirchner, T; Hansmann, M L; Burbat, L; von der Wall, E; Dietel, M; Hummel, M

    2018-04-01

    The simultaneous detection of multiple somatic mutations in the context of molecular diagnostics of cancer is frequently performed by means of amplicon-based targeted next-generation sequencing (NGS). However, only few studies are available comparing multicenter testing of different NGS platforms and gene panels. Therefore, seven partner sites of the German Cancer Consortium (DKTK) performed a multicenter interlaboratory trial for targeted NGS using the same formalin-fixed, paraffin-embedded (FFPE) specimen of molecularly pre-characterized tumors (n = 15; each n = 5 cases of Breast, Lung, and Colon carcinoma) and a colorectal cancer cell line DNA dilution series. Detailed information regarding pre-characterized mutations was not disclosed to the partners. Commercially available and custom-designed cancer gene panels were used for library preparation and subsequent sequencing on several devices of two NGS different platforms. For every case, centrally extracted DNA and FFPE tissue sections for local processing were delivered to each partner site to be sequenced with the commercial gene panel and local bioinformatics. For cancer-specific panel-based sequencing, only centrally extracted DNA was analyzed at seven sequencing sites. Subsequently, local data were compiled and bioinformatics was performed centrally. We were able to demonstrate that all pre-characterized mutations were re-identified correctly, irrespective of NGS platform or gene panel used. However, locally processed FFPE tissue sections disclosed that the DNA extraction method can affect the detection of mutations with a trend in favor of magnetic bead-based DNA extraction methods. In conclusion, targeted NGS is a very robust method for simultaneous detection of various mutations in FFPE tissue specimens if certain pre-analytical conditions are carefully considered.

  8. Molecular Interactions of Autophagy with the Immune System and Cancer

    Directory of Open Access Journals (Sweden)

    Yunho Jin

    2017-08-01

    Full Text Available Autophagy is a highly conserved catabolic mechanism that mediates the degradation of damaged cellular components by inducing their fusion with lysosomes. This process provides cells with an alternative source of energy for the synthesis of new proteins and the maintenance of metabolic homeostasis in stressful environments. Autophagy protects against cancer by mediating both innate and adaptive immune responses. Innate immune receptors and lymphocytes (T and B are modulated by autophagy, which represent innate and adaptive immune responses, respectively. Numerous studies have demonstrated beneficial roles for autophagy induction as well as its suppression of cancer cells. Autophagy may induce either survival or death depending on the cell/tissue type. Radiation therapy is commonly used to treat cancer by inducing autophagy in human cancer cell lines. Additionally, melatonin appears to affect cancer cell death by regulating programmed cell death. In this review, we summarize the current understanding of autophagy and its regulation in cancer.

  9. Molecular Epidemiology Investigation of Obesity and Lethal Prostate Cancer

    Science.gov (United States)

    2017-01-01

    epigenetic link between obesity and prostate cancer survival which will be explored in future studies. The support of the award has provided many...histone modifications in prostate cancer . Epigenetic inhibitors that target HDACs have been tested in clinical trials and approved by the US Food and...Drug Administration for use in treating specific cancers . Thus, understanding the specific role of obesity-related epigenetic events in prostate

  10. Definition of molecular determinants of prostate cancer cell bone extravasation.

    Science.gov (United States)

    Barthel, Steven R; Hays, Danielle L; Yazawa, Erika M; Opperman, Matthew; Walley, Kempland C; Nimrichter, Leonardo; Burdick, Monica M; Gillard, Bryan M; Moser, Michael T; Pantel, Klaus; Foster, Barbara A; Pienta, Kenneth J; Dimitroff, Charles J

    2013-01-15

    Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. However, whether these discrete prostate cancer cell-BMEC adhesive contacts culminate in cooperative, step-wise transendothelial migration into bone is not known. Here, we describe how metastatic prostate cancer cells breach BMEC monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed BMEC via sequential dependence on E-selectin ligands and β1 and αVβ3 integrins. Expression analysis in human metastatic prostate cancer tissue revealed that β1 was markedly upregulated compared with expression of other β subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1 GTPases and, notably, did not require exogenous chemokines as β1, αVβ3, Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer cell trafficking to murine femurs was dependent on E-selectin ligand, β1 integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing α1,3 fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically reduced prostate cancer incidence. These results unify the requirement for E-selectin ligands, α1,3 fucosyltransferases, β1 and αVβ3 integrins, and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone and offer new insight into the role of α1,3 fucosylation in prostate cancer development.

  11. Cisplatin in cancer therapy: molecular mechanisms of action

    OpenAIRE

    Dasari, Shaloam; Tchounwou, Paul Bernard

    2014-01-01

    Cisplatin, cisplatinum, or cis-diamminedichloroplatinum (II), is a well-known chemotherapeutic drug. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. It is effective against various types of cancers, including carcinomas, germ cell tumors, lymphomas, and sarcomas. Its mode of action has been linked to its ability to crosslink with the purine bases on the DNA; interfering with DNA repair mechanisms, causing DNA da...

  12. Molecular profiling of ADAM12 in human bladder cancer

    DEFF Research Database (Denmark)

    Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise

    2006-01-01

    PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...

  13. 'Molecular switch' vectors for hypoxia- and radiation-mediated gene therapy of cancer

    International Nuclear Information System (INIS)

    Greco, O.; Marples, B.; Joiner, M.C.; Scott, S.D.

    2003-01-01

    Intratumoral areas of low oxygen concentration are known to be refractive to radiotherapy treatment. However, this physiological condition can be exploited for selective cancer gene therapy. We have developed a series of synthetic promoters selectively responsive to both hypoxia and ionizing radiation (IR). These promoters contain hypoxia regulatory elements (HREs) from the erythropoietin (Epo), the phosphoglycerate kinase1(PGK1) and vascular endothelial growth factor (VEGF) genes, and/or IR-responsive CArG elements from the Early Growth Response 1 (Egr1) gene. The HRE and CArG promoters were able to regulate expression of reporter and suicide genes in human tumor cells, following corresponding stimulation with hypoxia (0.1% O2) or X-irradiation (5Gy) [Greco et al, 2002, Gene Therapy 9:1403]. Furthermore, the chimeric HRE + CArG promoters could be activated by these stimuli independently or even more significantly when given in combination, with the Epo HRE/CArG promoter proving to be the most responsive and robust. In order to amplify and maintain transgene expression even following withdrawal of the triggering stimuli, we have developed a 'molecular switch' system [Scott et al, 2000, Gene Therapy 7:1121]. This 'switch' system has now been engineered as a single vector molecule, containing HRE and CArG promoters. This new series of HRE/CArG switch vectors have been tested in a herpes simplex thymidine kinase (HSVtk)/ganciclovir (GCV) suicide gene assay. Results indicate that a) higher and more selective tumor cell kill is achieved with the switch when compared with the HRE and CArG promoters directly driving HSVtk expression and b) the Epo HRE/CArG switch vectors appear to function as efficiently as the strong constitutive cytomegalovirus (CMV) promoter construct

  14. Absorption, metabolism, anti-cancer effect and molecular targets of epigallocatechin gallate (EGCG): An updated review.

    Science.gov (United States)

    Gan, Ren-You; Li, Hua-Bin; Sui, Zhong-Quan; Corke, Harold

    2018-04-13

    Green tea is one of the most popular beverages in the world, especially in Asian countries. Consumption of green tea has been demonstrated to possess many health benefits, which mainly attributed to the main bioactive compound epigallocatechin gallate (EGCG), a flavone-3-ol polyphenol, in green tea. EGCG is mainly absorbed in the intestine, and gut microbiota play a critical role in its metabolism prior to absorption. EGCG exhibits versatile bioactivities, with its anti-cancer effect most attracting due to the cancer preventive effect of green tea consumption, and a great number of studies intensively investigated its anti-cancer effect. In this review, we therefore, first stated the absorption and metabolism process of EGCG, and then summarized its anti-cancer effect in vitro and in vivo, including its manifold anti-cancer actions and mechanisms, especially its anti-cancer stem cell effect, and next highlighted its various molecular targets involved in cancer inhibition. Finally, the anti-cancer effect of EGCG analogs and nanoparticles, as well as the potential cancer promoting effect of EGCG were also discussed. Understanding of the absorption, metabolism, anti-cancer effect and molecular targets of EGCG can be of importance to better utilize it as a chemopreventive and chemotherapeutic agent.

  15. From molecular imaging to personalized radionuclide therapy of cancer

    International Nuclear Information System (INIS)

    Baum, R.P.

    2015-01-01

    Full text of publication follows. 68 Gallium is a positron emitter (t 1/2 68 min) which can be produced from a generator in a convenient, 'in-house' preparation and used for labeling of peptides, e.g. somatostatin analogues (SA) like DOTATOC or DOTATATE for molecular imaging of SSTR expressing tumors. Since 2004, we have performed over 7700 68 Ga PET/CT studies in patients with neuroendocrine tumors (NET) and have established SSTR PET/CT as the new gold standard for imaging G1 and G2 NET (staging, re-staging, therapy response evaluation and detection of unknown primary NET). The same peptides can be labeled with 177 Lutetium or 90 Yttrium for radionuclide therapy, a form of personalized treatment (THERANOSTICS approach). PRRNT is based on the receptor-mediated internalization of SA. Several clinical trials indicate that PRRNT can deliver effective radiation doses to tumors. A German multi-institutional registry study with prospective follow up in 450 patients indicates that PRRT is an effective therapy for patients with G1-2 neuroendocrine tumors, irrespective of previous therapies, with a survival advantage of several years compared to other therapies and only minor side effects. Median overall survival (OS) of all patients from the start of treatment was 59 months. Median progression-free survival (PFS) measured from last cycle of therapy accounted to 41 mo. Median PFS of pancreatic NET was 39 mo. Similar results were obtained for NET of unknown primary (median PFS: 38 mo) whereas NET of small bowel had a median PFS of 51 months. Side effects like 3-4 NEThro- or hemato-toxicity were observed in only 0.2% and 2% of patients respectively. PRRNT is highly effective in the management of NET, even in advanced cases. In patients with progressive neuroendocrine tumors, fractionated, personalized PRRNT with lower doses of radioactivity given over a longer period of time (Bad Berka Concept using sequential (DUO) PRRNT) results in excellent therapeutic responses

  16. Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer.

    Science.gov (United States)

    Staquicini, Fernanda I; Qian, Ming D; Salameh, Ahmad; Dobroff, Andrey S; Edwards, Julianna K; Cimino, Daniel F; Moeller, Benjamin J; Kelly, Patrick; Nunez, Maria I; Tang, Ximing; Liu, Diane D; Lee, J Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R M; Lobb, Roy R; Edelman, Martin J; Sidman, Richard L; Wistuba, Ignacio I; Arap, Wadih; Pasqualini, Renata

    2015-03-20

    Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. Finally, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Molecular Biology and Prevention of Endometrial Cancer. Addendum

    National Research Council Canada - National Science Library

    Maxwell, George L

    2008-01-01

    Objective: To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC) therapy. Methods: 1...

  18. A Molecularly Targeted Theranostic Probe for Ovarian Cancer

    Science.gov (United States)

    Chen, Wenxue; Bardhan, Rizia; Bartels, Marc; Perez-Torres, Carlos; Pautler, Robia G.; Halas, Naomi J.; Joshi, Amit

    2014-01-01

    Overexpression of the human epidermal growth factor receptor (HER) family has been implicated in ovarian cancer because of its participation in signaling pathway regulating cellular proliferation, differentiation, motility, and survival. Currently, effective diagnostic and therapeutic schemes are lacking for treating ovarian cancer and consequently ovarian cancer has a high mortality rate. While HER2 receptor expression does not usually affect the survival rates of ovarian cancer to the same extent as in breast cancer, it can be employed as a docking site for directed nanotherapies in cases with de novo or acquired chemotherapy resistance. In this study, we have exploited a novel gold nanoshell-based complex (nanocomplex) for targeting, dual modal imaging, and photothermal therapy of HER2 overexpressing and drug resistant ovarian cancer OVCAR3 cells in vitro. The nanocomplexes are engineered to simultaneously provide contrast as fluorescence optical imaging probe and a magnetic resonance imaging (MRI) agent. Both immunofluorescence staining and MRI successfully demonstrate that nanocomplex-anti-HER2 conjugates specifically bind to OVCAR3 cells as opposed to the control, MDA-MB-231 cells, which have low HER2 expression. In addition, nanocomplexes targeted to OVCAR3 cells, when irradiated with near infrared (NIR) laser result in selective destruction of cancer cells through photothermal ablation. We also demonstrate that NIR light therapy and the nanocomplexes by themselves are non-cytotoxic in vitro. To the best of our knowledge, this is the first demonstration of a successful integration of dual modal bioimaging with photothermal cancer therapy for treatment of ovarian cancer. Based on their efficacy in vitro, these nanocomplexes are highly promising for image guided photo-thermal therapy of ovarian cancer as well as other HER2 overexpressing cancers. PMID:20371708

  19. The Genetics and Molecular Alterations of Pancreatic Cancer

    NARCIS (Netherlands)

    Wilde, R.F. de

    2015-01-01

    The prospect that pancreatic cancer will be the second most common cause of cancer death by 2030 is worrisome. Considering that the approximate 6% overall 5-year survival has not merely changed in the past decades illustrates the need to revert the bleak prognosis. Centralization of surgery

  20. 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.

  1. The effect of fasting on the important molecular mechanisms related to cancer treatment

    Directory of Open Access Journals (Sweden)

    Vahideh Keyvani

    2014-11-01

    Full Text Available Fasting does have remarkable benefits in the treatment of cancer and another diseases such as metabolic syndrome, diabetes, and a multitude of other chronic diseases. It has been determined that fasting could play an important role during cancer treatment and progression via the regulation of insulin-like growth factor-1 (IGF-1 as well as other growth factors. Also, it has been shown that fasting would enhance the chemotherapy effect in cancer patients, selectively protects normal cells and organisms from chemotherapy toxicity, while simultaneously sensitizing tumors. In this article, we discuss the benefits of fasting in the treatment of cancer through several different molecular pathways.

  2. 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.

  3. [Molecular-Genetic Diagnosis and Molecular-Targeted Therapy in Cancer: Challenges in the Era of Precision Medicine].

    Science.gov (United States)

    Miyachi, Hayato

    2015-10-01

    Elucidation of the molecular pathogenesis of neoplasms and application of emerging technologies for testing and therapy have resulted in a series of paradigm shifts in patient care, from conventional to personalized medicine. This has been promoted by companion diagnostics and molecular targeted therapy, tailoring the treatment to the individual characteristics of each patient. Precision oncology has been accelerated by integrating the enhanced resolution of molecular analysis, mechanism clarity, and therapeutic relevance through genomic knowledge. In its clinical implementation, there are laboratory challenges concerning accurate measurement using stored samples, differentiation between driver and passenger mutations as well as between germline and somatic mutations, bioinformatics availability, practical decision-making algorithms, and ethical issues regarding incidental findings. The medical laboratory has a new role in providing not only testing services but also an instructive approach to users to ensure the sample quality and privacy protection of personal genome information, supporting the quality of patient practice based on laboratory diagnosis.

  4. Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer

    Science.gov (United States)

    Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei

    2014-11-01

    Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

  5. Hereditary breast cancer: from molecular pathology to tailored therapies.

    Science.gov (United States)

    Tan, D S P; Marchiò, C; Reis-Filho, J S

    2008-10-01

    Hereditary breast cancer accounts for up to 5-10% of all breast carcinomas. Recent studies have demonstrated that mutations in two high-penetrance genes, namely BRCA1 and BRCA2, are responsible for about 16% of the familial risk of breast cancer. Even though subsequent studies have failed to find another high-penetrance breast cancer susceptibility gene, several genes that confer a moderate to low risk of breast cancer development have been identified; moreover, hereditary breast cancer can be part of multiple cancer syndromes. In this review we will focus on the hereditary breast carcinomas caused by mutations in BRCA1, BRCA2, Fanconi anaemia (FANC) genes, CHK2 and ATM tumour suppressor genes. We describe the hallmark histological features of these carcinomas compared with non-hereditary breast cancers and show how an accurate histopathological diagnosis may help improve the identification of patients to be screened for mutations. Finally, novel therapeutic approaches to treat patients with BRCA1 and BRCA2 germ line mutations, including cross-linking agents and PARP inhibitors, are discussed.

  6. Molecular markers for urothelial bladder cancer prognosis: toward implementation in clinical practice.

    Science.gov (United States)

    van Rhijn, Bas W G; Catto, James W; Goebell, Peter J; Knüchel, Ruth; Shariat, Shahrokh F; van der Poel, Henk G; Sanchez-Carbayo, Marta; Thalmann, George N; Schmitz-Dräger, Bernd J; Kiemeney, Lambertus A

    2014-10-01

    To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to provide directions toward implementation of molecular markers in future clinical decision making. Immunohistochemistry, gene signatures, and FGFR3-based molecular grading were used as molecular examples focussing on prognostics and issues related to robustness of pathological and molecular assays. The role of molecular markers to predict recurrence is limited, as clinical variables are currently more important. The prediction of progression and survival using molecular markers holds considerable promise. Despite a plethora of prognostic (clinical and molecular) marker studies, reproducibility of pathology and molecular assays has been understudied, and lack of reproducibility is probably the main reason that individual prediction of disease outcome is currently not reliable. Molecular markers are promising to predict progression and survival, but not recurrence. However, none of these are used in the daily clinical routine because of reproducibility issues. Future studies should focus on reproducibility of marker assessment and consistency of study results by incorporating scoring systems to reduce heterogeneity of reporting. This may ultimately lead to incorporation of molecular markers in clinical practice. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. SOFTWARE REVIEW: The Advanced Physics Virtual Laboratory Series: CD-ROM Thermodynamics and Molecular Physics

    Science.gov (United States)

    Dobson, Ken

    1998-09-01

    The program installed easily although the inexperienced might be as terrified as I was by the statements threatening to delete various files it had found on my machine. However, I ignored these and all went well. The user is faced with a menu of 14 simulations covering molecular topics such as the Kinetic Model of an Ideal Gas, Diffusion (through a variable diameter aperture) and a Semi-permeable Membrane, the Maxwell Distribution and Brownian Motion. Thermodynamics is covered by simulations of ideal-gas behaviour at constant pressure, volume and temperature. This is extended to deal with adiabatic changes, the work done by and on a gas, specific heats, work cycles, and to the behaviour of real gases in evaporation and condensation. Finally there are short video-clips of actual experiments showing gas and vapour behaviour. Each simulation is displayed in a `picture window' which gives a qualitative display of how molecules are moving in a container, or how a parameter changes as conditions are varied, as appropriate. Attached (somewhat loosely as it turned out) to these are relevant graphs showing how the important variables such as temperature, volume and pressure change as conditions are changed. The simulations are dynamic and set off by clicking on a RUN button. The simulation can be stopped at any stage and reset to change parameters. It is easy to change the conditions of the simulation by moving sliders along a scale. I particularly liked the simulations of molecular behaviour and the isotherms of a real gas - an ideal case for animation. Each simulation has a short spoken commentary which you can switch in, a brief drop-down text describing the simulation, and a single question. This is where, I felt, things started to go wrong. The simulation displays are informative and give a good visual impression of a part of physics that students find abstract and difficult. But the supporting commentary and text are much too thin for, say, `supported self

  8. Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

    International Nuclear Information System (INIS)

    Mahajan, A.; Goh, V.; Basu, S.; Vaish, R.; Weeks, A.J.; Thakur, M.H.; Cook, G.J.

    2015-01-01

    Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure–function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [ 18 F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed “theranostics”. Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research. -- Highlights: •Molecular functional imaging (MFI) gives insight into the tumor biology and intratumoral heterogeneity. •It has potential role in identifying radiomic signatures associated with underlying gene-expression. •Radiomics can be used to create a road map

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

    Directory of Open Access Journals (Sweden)

    Sundus Iqbal

    2014-03-01

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

  10. 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

  11. Association Between Imaging Characteristics and Different Molecular Subtypes of Breast Cancer.

    Science.gov (United States)

    Wu, Mingxiang; Ma, Jie

    2017-04-01

    Breast cancer can be divided into four major molecular subtypes based on the expression of hormone receptor (estrogen receptor and progesterone receptor), human epidermal growth factor receptor 2, HER2 status, and molecular proliferation rate (Ki67). In this study, we sought to investigate the association between breast cancer subtype and radiological findings in the Chinese population. Medical records of 300 consecutive invasive breast cancer patients were reviewed from the database: the Breast Imaging Reporting and Data System. The imaging characteristics of the lesions were evaluated. The molecular subtypes of breast cancer were classified into four types: luminal A, luminal B, HER2 overexpressed (HER2), and basal-like breast cancer (BLBC). Univariate and multivariate logistic regression analyses were performed to assess the association between the subtype (dependent variable) and mammography or 15 magnetic resonance imaging (MRI) indicators (independent variables). Luminal A and B subtypes were commonly associated with "clustered calcification distribution," "nipple invasion," or "skin invasion" (P cancers showed association with persistent enhancement in the delayed phase on MRI and "clustered calcification distribution" on mammography (P breast tumor, which are potentially useful tools in the diagnosis and subtyping of breast cancer. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  12. Raman spectroscopic analysis for gastric and colorectal cancer in surgical treatment toward molecular-guided surgery

    Science.gov (United States)

    Koga, Shigehiro; Watanabe, Yuji; Oshima, Yusuke

    2018-02-01

    Raman spectroscopy provides a wealth of diagnostic information to the surgeon with in situ cancer detection and label-free histopathology in intraoperative conditions. Raman spectroscopy is a promising optical technique which can analyze biological tissues with light scattering. The difference in frequencies between the incident light and the scattering light are called Raman shifts, which correspond to the vibrational energy of the molecular bonds. Raman spectrum gives information about the molecular structure and composition in biological specimens. We had been previously reported that Raman spectroscopy could distinguish various histological types of human lung cancer cells from normal cells in vitro, and also confirmed that Raman spectra obtained from cancer cells and their environment including other cells and extracellular matrix in xenograft models and spontaneous metastasis models were distinguishable using Raman spectroscopy combined with fluorescence microscopy and photoluminescence imaging. Malignancy can be characterized not only by the cancer cells but also by the environmental factors including immune cells, stroma cells, secretion vesicles and extracellular matrix, but to identify and detect cancer diagnostic biomarkers in vivo on Raman spectroscopy is still challenging. Here we investigate morphological and molecular dynamics in advanced cancer specimens obtained from patients. We are also constructing a customdesigned Raman spectral imaging system for both in vitro and in vivo assay of tumor tissues to reveal the metastasis process and to evaluate therapeutic effects of anti-cancer drugs and their drug delivery toward the clinical application of the technique.

  13. Molecular genetic approach for screening of hereditary non-polyposis colorectal cancer

    Directory of Open Access Journals (Sweden)

    Metka Ravnik-Glavač

    2005-07-01

    Full Text Available Background: The main goal of knowledge concerning human diseases is to transfer as much as possible useful information into clinical applications. Hereditary non-polyposis colorectal cancer (HNPCC is the most common autosomal dominant inherited predisposition for colorectal cancer, accounting for 1–2% of all bowel cancer. The only way to diagnose HNPCC is by a family history consistent with the disease defined by International Collaborative Group on HNPCC (Amsterdam criteria I and II. The main molecular cause of HNPCC is a constitutional mutation in one of the mismatch repair (MMR genes. Since HNPCC mutations have been detected also in families that did not fulfil the Amsterdam criteria, molecular genetic characteristics of HNPCC cancers have been proposed as valuable first step in HNPCC identification. Microsatellite instability is present in about 90% of cancers of HNPCC patients. However, of all MSI colorectal cancers 80– 90% are sporadic. Several molecular mechanisms have been uncovered that enable distinguishing to some extent between sporadic and HNPCC cancers with MSI including hypermethylation of hMLH1 promoter and frequent mutations in BAX and TGFBR2 in sporadic CRC with MSI-H.Conclusions: The determination of MSI status and careful separation of MSI positive colorectal cancer into sporadic MSIL, sporadic MSI-H, and HNPCC MSI-H followed by mutation detection in MMR genes is important for prevention, screening and management of colorectal cancer. In some studies we and others have already shown that large-scale molecular genetic analysis for HNPCC can be done and is sensitive enough to approve population screening. Population screening includes also colonoscopy which is restricted only to the obligate carriers of the mutation. This enables that the disease is detected in earlier stages which would greatly decrease medical treatment costs and most importantly decrease mortality. In Slovenia we have started population screening based

  14. Breast cancer in Ethiopia: evidence for geographic difference in the distribution of molecular subtypes in Africa.

    Science.gov (United States)

    Hadgu, Endale; Seifu, Daniel; Tigneh, Wondemagegnhu; Bokretsion, Yonas; Bekele, Abebe; Abebe, Markos; Sollie, Thomas; Merajver, Sofia D; Karlsson, Christina; Karlsson, Mats G

    2018-02-14

    Breast cancer is a heterogeneous disease with several morphological and molecular subtypes. Widely accepted molecular classification system uses assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker Ki67. Few studies have been conducted on the incidence and molecular types of breast cancer in Sub-Saharan Africa. Previous studies mainly from Western and Central Africa, showed breast cancer to occur at younger ages and to present with aggressive features, such as high-grade, advanced stage and triple-negative phenotype (negative for ER, PR and HER2). Limited data from East Africa including Ethiopia however shows hormone receptor negative tumors to account for a lower proportion of all breast cancers than has been reported from elsewhere in Africa. In this study from Tikur Anbessa Specialized Hospital, 114 breast cancer patients diagnosed between 2012 and 2015 were enrolled. ER, PR, Ki67 and HER2 receptor status were assessed using immunohistochemistry from tissue microarrays. FISH was used for assessment of gene amplification in all equivocal tumor samples and for confirmation in HER2-enriched cases. The distribution of molecular subtypes was: Luminal A: 40%; Luminal B: 26%; HER2-enriched: 10%; TNBC: 23%. ER were positive in 65% of all tumors and 43% the cases were positive for PR. There was statistically significant difference in median age at diagnosis between the molecular subtypes (P molecular subtypes in different age ranges with Luminal B subtype being more common at younger ages (median = 36) and Luminal A subtype more prevalent at older ages (median = 42). There were no statistically significant differences in tumor grade, histology, and stage between the molecular subtypes of breast cancer. The present study detected Luminal A breast cancer to be the most common subtype and reveals a relatively low rate of hormone receptor negative and TNBC. Our findings and

  15. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    Directory of Open Access Journals (Sweden)

    Hsu Hui-Chi

    2011-04-01

    Full Text Available Abstract Background Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Methods Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. Results We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was

  16. Correlation of microarray-based breast cancer molecular subtypes and clinical outcomes: implications for treatment optimization

    International Nuclear Information System (INIS)

    Kao, Kuo-Jang; Chang, Kai-Ming; Hsu, Hui-Chi; Huang, Andrew T

    2011-01-01

    Optimizing treatment through microarray-based molecular subtyping is a promising method to address the problem of heterogeneity in breast cancer; however, current application is restricted to prediction of distant recurrence risk. This study investigated whether breast cancer molecular subtyping according to its global intrinsic biology could be used for treatment customization. Gene expression profiling was conducted on fresh frozen breast cancer tissue collected from 327 patients in conjunction with thoroughly documented clinical data. A method of molecular subtyping based on 783 probe-sets was established and validated. Statistical analysis was performed to correlate molecular subtypes with survival outcome and adjuvant chemotherapy regimens. Heterogeneity of molecular subtypes within groups sharing the same distant recurrence risk predicted by genes of the Oncotype and MammaPrint predictors was studied. We identified six molecular subtypes of breast cancer demonstrating distinctive molecular and clinical characteristics. These six subtypes showed similarities and significant differences from the Perou-Sørlie intrinsic types. Subtype I breast cancer was in concordance with chemosensitive basal-like intrinsic type. Adjuvant chemotherapy of lower intensity with CMF yielded survival outcome similar to those of CAF in this subtype. Subtype IV breast cancer was positive for ER with a full-range expression of HER2, responding poorly to CMF; however, this subtype showed excellent survival when treated with CAF. Reduced expression of a gene associated with methotrexate sensitivity in subtype IV was the likely reason for poor response to methotrexate. All subtype V breast cancer was positive for ER and had excellent long-term survival with hormonal therapy alone following surgery and/or radiation therapy. Adjuvant chemotherapy did not provide any survival benefit in early stages of subtype V patients. Subtype V was consistent with a unique subset of luminal A intrinsic

  17. Molecular Epidemiology of Breast Cancer in Korean Women

    National Research Council Canada - National Science Library

    Gabrielson, Edward

    2002-01-01

    ... profiles as objective measures of breast cancer phenotypes. The study is being conducted using samples from Korean women because this likely represents a relatively homogeneous population from genetic and cultural perspectives...

  18. Molecular alterations in endometrial cancer : implications for clinical management

    NARCIS (Netherlands)

    Stelloo, E.

    2017-01-01

    Over the last decades, advances have been made in the treatment of endometrial cancer. The clinicopathological risk stratification for postoperative therapy has considerably reduced overtreatment by refining indications and introducing treatment with fewer side effects. Despite refinement in the use

  19. Clinical impact of molecular analysis on thyroid cancer management

    NARCIS (Netherlands)

    Wreesmann, Volkert B.; Singh, Bhuvanesh

    2008-01-01

    Thyroid cancer constitutes a progressive continuum of disease ranging from indolent well-differentiated carcinomas to aggressive poorly differentiated carcinomas and universally fatal anaplastic carcinomas. The wide divergence in clinical behavior is poorly predicted for by current

  20. Molecular Landscape of Non-Muscle Invasive Bladder Cancer.

    Science.gov (United States)

    Meeks, Joshua J; Lerner, Seth P

    2017-11-13

    In this issue of Cancer Cell, Hurst et al. report an integrated analysis of non-invasive (stage Ta) bladder cancer. Two genomic subtypes are distinguished by chromosome 9q loss, resulting in increased AKT/PI3K/mTOR signaling. Tumors from female patients have a higher frequency of KDM6A mutations. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Exploring the molecular targets of dietary flavonoid fisetin in cancer

    OpenAIRE

    Syed, Deeba N.; Adhami, Vaqar Mustafa; Khan, Naghma; Khan, Mohammad Imran; Mukhtar, Hasan

    2016-01-01

    The last few decades have seen a resurgence of interest among the scientific community in exploring the efficacy of natural compounds against various human cancers. Compounds of plant origin belonging to different groups such as alkaloids, flavonoids and polyphenols evaluated for their cancer preventive effects have yielded promising data, thereby offering a potential therapeutic alternative against this deadly disease. The flavonol fisetin (3,3′,4′,7-tetrahydroxyflavone), present in fruits a...

  2. Breast Cancer Mortality in African-American and Non-Hispanic White Women by Molecular Subtype and Stage at Diagnosis: A Population-Based Study.

    Science.gov (United States)

    Tao, Li; Gomez, Scarlett Lin; Keegan, Theresa H M; Kurian, Allison W; Clarke, Christina A

    2015-07-01

    Higher breast cancer mortality rates for African-American than non-Hispanic White women are well documented; however, it remains uncertain if this disparity occurs in disease subgroups defined by tumor molecular markers and stage at diagnosis. We examined racial differences in outcome according to subtype and stage in a diverse, population-based series of 103,498 patients. We obtained data for all invasive breast cancers diagnosed between January 1, 2005, and December 31, 2012, and followed through December 31, 2012, among 93,760 non-Hispanic White and 9,738 African-American women in California. Molecular subtypes were categorized according to tumor expression of hormone receptor (HR, based on estrogen and progesterone receptors) and human epidermal growth factor receptor 2 (HER2). Cox proportional hazards models were used to calculate relative hazard (RH) and 95% confidence intervals (CI) for breast cancer-specific mortality. After adjustment for patient, tumor, and treatment characteristics, outcomes were comparable by race for stage I or IV cancer regardless of subtype, and HR(+)/HER2(+) or HR(-)/HER2(+) cancer regardless of stage. We found substantially higher hazards of breast cancer death among African-American women with stage II/III HR(+)/HER2(-) (RH, 1.31; 95% CI, 1.03-1.65; and RH, 1.39; 95% CI, 1.10-1.75, respectively) and stage III triple-negative cancers relative to Whites. There are substantial racial/ethnic disparities among patients with stages II/III HR(+)/HER2(-) and stage III triple-negative breast cancers but not for other subtype and stage. These data provide insights to assess barriers to targeted treatment (e.g., trastuzumab or endocrine therapy) of particular subtypes of breast cancer among African-American patients. ©2015 American Association for Cancer Research.

  3. Cellular and Molecular Mechanisms of 3,3′-Diindolylmethane in Gastrointestinal Cancer

    Directory of Open Access Journals (Sweden)

    Soo Mi Kim

    2016-07-01

    Full Text Available Studies in humans have shown that 3,3′-diindolylmethane (DIM, which is found in cruciferous vegetables, such as cabbage and broccoli, is effective in the attenuation of gastrointestinal cancers. This review presents the latest findings on the use, targets, and modes of action of DIM for the treatment of human gastrointestinal cancers. DIM acts upon several cellular and molecular processes in gastrointestinal cancer cells, including apoptosis, autophagy, invasion, cell cycle regulation, metastasis, angiogenesis, and endoplasmic reticulum (ER stress. In addition, DIM increases the efficacy of other drugs or therapeutic chemicals when used in combinatorial treatment for gastrointestinal cancer. The studies to date offer strong evidence to support the use of DIM as an anticancer and therapeutic agent for gastrointestinal cancer. Therefore, this review provides a comprehensive understanding of the preventive and therapeutic properties of DIM in addition to its different perspective on the safety of DIM in clinical applications for the treatment of gastrointestinal cancers.

  4. Considerations for standardizing predictive molecular pathology for cancer prognosis.

    Science.gov (United States)

    Fiorentino, Michelangelo; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2017-01-01

    Molecular tests that were once ancillary to the core business of cyto-histopathology are becoming the most relevant workload in pathology departments after histopathology/cytopathology and before autopsies. This has resulted from innovations in molecular biology techniques, which have developed at an incredibly fast pace. Areas covered: Most of the current widely used techniques in molecular pathology such as FISH, direct sequencing, pyrosequencing, and allele-specific PCR will be replaced by massive parallel sequencing that will not be considered next generation, but rather, will be considered to be current generation sequencing. The pre-analytical steps of molecular techniques such as DNA extraction or sample preparation will be largely automated. Moreover, all the molecular pathology instruments will be part of an integrated workflow that traces the sample from extraction to the analytical steps until the results are reported; these steps will be guided by expert laboratory information systems. In situ hybridization and immunohistochemistry for quantification will be largely digitalized as much as histology will be mostly digitalized rather than viewed using microscopy. Expert commentary: This review summarizes the technical and regulatory issues concerning the standardization of molecular tests in pathology. A vision of the future perspectives of technological changes is also provided.

  5. The molecular biology of prostate cancer: current understanding and clinical implications.

    Science.gov (United States)

    Gandhi, Jason; Afridi, Adil; Vatsia, Sohrab; Joshi, Gargi; Joshi, Gunjan; Kaplan, Steven A; Smith, Noel L; Khan, Sardar Ali

    2018-04-01

    With continuous progress over the past few decades in understanding diagnosis, treatment, and genetics, much has been learned about the prostate cancer-diagnosed genome. A comprehensive MEDLINE® and Google scholar literature search was conducted using keyword variations relating to the genetics of prostate cancer such as chromosomal alterations, androgen receptor, castration-resistant, inheritance, polymorphisms, oncogenes, metastasis, biomarkers, and immunotherapy. Traditionally, androgen receptors (AR) have been the focus of research. Recently, identification of recurrent chromosomal alterations that lead to either multiplication of regions (gain-of-function) or deletion of regions (loss-of-function) has opened the door to greater genetic accessibility. These chromosomal aberrations lead to variation in copy number and gene expression. Some of these chromosomal alterations are inherited, while others undergo somatic mutations during disease progression. Inherited gene mutations that make one susceptible to prostate cancer have been identified with familial-linked studies. Somatic genes that progress tumorigenesis have also been identified. Research on the molecular biology of prostate cancer has characterized these genes into tumor suppressor genes or oncogenes. Additionally, genome-wide assay studies have identified many high-risk single-nucleotide polymorphisms recurrent throughout the prostate cancer-diagnosed genome. Castration-resistant prostate cancer is the most aggressive form of prostate cancer, and its research has elucidated many types of mutations associated with AR itself, including enhanced expression and amplification, point mutations, and alternative splicing. Understanding the molecular biology of prostate cancer has permitted more accurate identification using advanced biomarkers and therapy for aggressive forms using immunotherapy. An age-related disease, prostate cancer commands profound attention. With increasing life expectancy and the

  6. Managing cancer-related venous thromboembolic disease: low-molecular-weight heparins and beyond.

    Science.gov (United States)

    O'Connell, Casey L; Liebman, Howard A

    2008-12-01

    Venous thromboembolism is a major contributor to the morbidity and mortality of patients with cancer. For patients undergoing cancer surgery, several trials support the safety and efficacy of unfractionated heparin and of low-molecular-weight heparin for the prevention of venous thromboembolism, while data regarding the efficacy and safety of these agents in the setting of medical hospitalization is less definitive and must be extracted from trials including noncancer patients with different thrombotic risk factors. Randomized clinical studies confirm that patients with cancer who develop venous thromboembolism have superior outcomes when treated with long-term low-molecular-weight heparin as compared with warfarin. Novel anticoagulants that are orally bioavailable and function by directly inhibiting factor Xa or thrombin are entering the market. To date, data regarding the efficacy and safety of these novel anticoagulants as venous thromboembolism prophylaxis and treatment in cancer patients are not available and must be extracted from larger trials with heterogeneous patient populations.

  7. Treatment outcome in patients with triple negative early stage breast cancers compared with other molecular subtypes

    International Nuclear Information System (INIS)

    Kim, Ja Young; Chang, Sei Kyung; Lee, Bo Mi; Shin, Hyun Soo; Park, Heily

    2012-01-01

    To determine whether triple negative (TN) early stage breast cancers have poorer survival rates compared with other molecular types. Between August 2000 and July 2006, patients diagnosed with stage I, II early stage breast cancers, in whom all three markers (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor [HER]-2) were available and treated with modified radical mastectomy or breast conserving surgery followed by radiotherapy, were retrospectively reviewed. Of 446 patients, 94 (21.1%) were classified as TN, 57 (12.8%) as HER-2 type, and 295 (66.1%) as luminal. TN was more frequently associated with young patients younger than 35 years old (p = 0.002), higher histologic grade (p 0.05). We found that patients with TN early stage breast cancers had no difference in survival rates compared with other molecular subtypes. Prospective study in homogeneous treatment group will need for a prognosis of TN early stage breast cancer.

  8. Molecular epidemiology, and possible real-world applications in breast cancer.

    Science.gov (United States)

    Ito, Hidemi; Matsuo, Keitaro

    2016-01-01

    Gene-environment interaction, a key idea in molecular epidemiology, has enabled the development of personalized medicine. This concept includes personalized prevention. While genome-wide association studies have identified a number of genetic susceptibility loci in breast cancer risk, however, the application of this knowledge to practical prevention is still underway. Here, we briefly review the history of molecular epidemiology and its progress in breast cancer epidemiology. We then introduce our experience with the trial combination of GWAS-identified loci and well-established lifestyle and reproductive risk factors in the risk prediction of breast cancer. Finally, we report our exploration of the cumulative risk of breast cancer based on this risk prediction model as a potential tool for individual risk communication, including genetic risk factors and gene-environment interaction with obesity.

  9. An NRG Oncology/GOG study of molecular classification for risk prediction in endometrioid endometrial cancer.

    Science.gov (United States)

    Cosgrove, Casey M; Tritchler, David L; Cohn, David E; Mutch, David G; Rush, Craig M; Lankes, Heather A; Creasman, William T; Miller, David S; Ramirez, Nilsa C; Geller, Melissa A; Powell, Matthew A; Backes, Floor J; Landrum, Lisa M; Timmers, Cynthia; Suarez, Adrian A; Zaino, Richard J; Pearl, Michael L; DiSilvestro, Paul A; Lele, Shashikant B; Goodfellow, Paul J

    2018-01-01

    The purpose of this study was to assess the prognostic significance of a simplified, clinically accessible classification system for endometrioid endometrial cancers combining Lynch syndrome screening and molecular risk stratification. Tumors from NRG/GOG GOG210 were evaluated for mismatch repair defects (MSI, MMR IHC, and MLH1 methylation), POLE mutations, and loss of heterozygosity. TP53 was evaluated in a subset of cases. Tumors were assigned to four molecular classes. Relationships between molecular classes and clinicopathologic variables were assessed using contingency tests and Cox proportional methods. Molecular classification was successful for 982 tumors. Based on the NCI consensus MSI panel assessing MSI and loss of heterozygosity combined with POLE testing, 49% of tumors were classified copy number stable (CNS), 39% MMR deficient, 8% copy number altered (CNA) and 4% POLE mutant. Cancer-specific mortality occurred in 5% of patients with CNS tumors; 2.6% with POLE tumors; 7.6% with MMR deficient tumors and 19% with CNA tumors. The CNA group had worse progression-free (HR 2.31, 95%CI 1.53-3.49) and cancer-specific survival (HR 3.95; 95%CI 2.10-7.44). The POLE group had improved outcomes, but the differences were not statistically significant. CNA class remained significant for cancer-specific survival (HR 2.11; 95%CI 1.04-4.26) in multivariable analysis. The CNA molecular class was associated with TP53 mutation and expression status. A simple molecular classification for endometrioid endometrial cancers that can be easily combined with Lynch syndrome screening provides important prognostic information. These findings support prospective clinical validation and further studies on the predictive value of a simplified molecular classification system. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2017-01-01

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

  11. Correlativity study on MRI morphologic features, pathology, and molecular biology of breast cancer

    International Nuclear Information System (INIS)

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

    2004-01-01

    Objective: To investigate the correlation among MRI morphologic features, pathology, and molecular biology of breast cancer. Methods: MR scanning was performed in 78 patients with breast cancer before operation and MRI morphologic features of breast cancer were analyzed. The mastectomy specimens of the breast neoplasm were stained with immunohistochemistry, and the expression of estrogen receptor (ER), progesterone receptor (PR), C-erbB-2, p53, and the distribution of microvessel density (MVD) was measured. The pathologic results were compared with MRI features. Results: Among the 80 breast cancers, ER positive expression was positively correlated with the spiculate margin of breast cancer (P 0.05). Among the 41 breast cancers with dynamic MR scans, there was positive correlation between the spatial distribution of contrast agent and MVD (P<0.01). Conclusion: There exists some correlation among MRI morphologic features, pathology, and molecular biology factors in breast cancer to certain extent. The biologic behavior and prognosis of the breast cancer can be assessed according to MRI features

  12. 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.

  13. Fanconi anaemia: genetics, molecular biology, and cancer – implications for clinical management in children and adults.

    Science.gov (United States)

    Schneider, M; Chandler, K; Tischkowitz, M; Meyer, S

    2015-07-01

    Fanconi anaemia (FA) is an inherited disease with congenital and developmental abnormalities, cross-linker hypersensitivity and extreme cancer predisposition. With better understanding of the genetic and molecular basis of the disease, and improved clinical management, FA has been transformed from a life-limiting paediatric disease to an uncommon chronic condition that needs lifelong multidisciplinary management, and a paradigm condition for the understanding of the gene-environment interaction in the aetiology of congenital anomalies, haematopoiesis and cancer development. Here we review genetic, molecular and clinical aspects of FA, and discuss current controversies and future prospects. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Molecular alterations in childhood thyroid cancer after Chernobyl accident and low-dose radiation risk

    International Nuclear Information System (INIS)

    Suzuki, Keiji; Mitsutake, Norisato; Yamashita, Shunichi

    2012-01-01

    The linear no-threshold (LNT) model of radiation carcinogenesis has been used for evaluating the risk from radiation exposure. While the epidemiological studies have supported the LNT model at doses above 100 mGy, more uncertainties are still existed in the LNT model at low doses below 100 mGy. Thus, it is urged to clarify the molecular mechanisms underlying radiation carcinogenesis. After the Chernobyl accident in 1986, significant amount of childhood thyroid cancer has emerged in the children living in the contaminated area. As the incidence of sporadic childhood thyroid cancer is very low, it is quite evident that those cancer cases have been induced by radiation exposure caused mainly by the intake of contaminated foods, such as milk. Because genetic alterations in childhood thyroid cancers have extensively been studied, it should provide a unique chance to understand the molecular mechanisms of radiation carcinogenesis. In a current review, molecular signatures obtained from the molecular studies of childhood thyroid cancer after Chernobyl accident have been overviewed, and new roles of radiation exposure in thyroid carcinogenesis will be discussed. (author)

  15. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer.

    Science.gov (United States)

    Ahn, Byeong-Cheol

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term "theranostics" was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging.

  16. Urinary high molecular weight matrix metalloproteinases as non-invasive biomarker for detection of bladder cancer

    OpenAIRE

    Mohammed, Mohammed A; Seleim, Manar F; Abdalla, Mohga S; Sharada, Hayat M; Abdel Wahab, Abdel Hady A

    2013-01-01

    Background Matrix Metalloproteinases (MMPs) are key molecules for tumor growth, invasion and metastasis. Over-expression of different MMPs in tumor tissues can disturb the homeostasis and increase the level of various body fluids. Many MMPs including high molecular weights (HMWs) were detected in the urine of prostate and bladder cancer patients. Our aim here is to assess the usefulness of HMW MMPs as non invasive biomarkers in bilharzial bladder cancer in Egyptian patients. Methods The activ...

  17. Utilizing Endoscopic Ultrasound-Guided Fine Needle Aspiration in Identifying Molecular Targets for Pancreatic Cancer

    OpenAIRE

    Onyekachi Henry Ogbonna; Muhammad Wasif Saif

    2013-01-01

    Pancreatic cancer remains a devastating disease, with poor survival rates and high recurrence rates with current treatmentregimens. Over the years we have come to understand the complex biology of this cancer, involving cross-talking signalingpathways that proffers resistance to current therapy. Several molecularly targeted agents remain in development. At the2013 American Society of Clinical Oncology (ASCO) Annual Meeting, an abstract (#4051) was presented which exploredusing endoscopic ultr...

  18. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data

    OpenAIRE

    REN, ZHONGLU; WANG, WENHUI; LI, JINMING

    2015-01-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristi...

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

    International Nuclear Information System (INIS)

    Joshi, Bishnu P.; Wang, Thomas D.

    2010-01-01

    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

  20. Evaluation of coexistence of cancer and active tuberculosis; 16 case series

    Directory of Open Access Journals (Sweden)

    Beyhan Çakar

    Full Text Available Introduction: Tuberculosis is an important risk factor for cancer. Pulmonary TB and lung cancer(LC may mimic each other especially in the aspect of the clinical and radiological features. The aim of the study was to evaluate the features and risk factors of cases with coexistence cancer and active TB. Methodology: We retrospectively reviewed the medical records of patients with coexisting TB and cancer a period from 2009 to 2014. We evaluated demographic data, the ways diagnosis of TB cases, the location of TB and cancer, TB treatment results of the cases. Results: We recorded 374 TB cases in our dyspensary at this study period. In 16 (4% of these cases, a coexistence of cancer and TB was detected. The male/female ratio was 12/4. The mean age was 62,12 ± 15,13 years. There were TST results except three cases. There were ten pulmonary TB and six extra-pulmonary TB (four peripheral lymphadenopathy TB, one abdominal TB lymphadenopathy and one salivary gland TB. Cancer types were as follows; eight lung cancer, two breast cancer, one base of tongue, one endometrium cancer, one hypopharyngeal cancer, one stomach cancer, one bladder cancer and one maxillary cancer. Diagnosis of all cases was confirmed by bacteriologic and/or histopathological examination. Squamous cell carcinoma was the most common type of cancers. This rate was 9/16. All TB cases were new. There were risk factors out of two case in the cases. Five cases were died during TB treatment. Others completed TB treatment without any complication. Conclusions: In our study, the coexistence of LC and pulmonary TB was more common. The local immunity is deteriorated in cancer cases. If there is pulmonary infiltrates in lung or peripheral lymphadenopathy, we must search tuberculosis too out of metastatic lesion and other infectious diseases. We should not make delay in the diagnosis of active TB in cancer cases. Keywords: Coexistent, Cancer, Tuberculosis, Tuberculosis treatment

  1. Metastatic Organotropism: An Intrinsic Property of Breast Cancer Molecular Subtypes.

    Science.gov (United States)

    Wei, Shi; Siegal, Gene P

    2017-03-01

    It has long been known that some cancers have the propensity to metastasize to certain organs thus creating a nonrandom distribution of sites for distant relapse, a phenomenon known as "metastatic organotropism." Some of these examples include ovary primary to abdominal cavity, prostate primary to bone, and pancreas primary to liver. In contrast, other tumor types, such as mammary and renal cell carcinoma, can relapse in multiple organs although approximately half of advanced breast cancers metastasize to bone. On the other hand gene expression profiling studies have identified various breast cancer classes with prognostic significance. Recent studies have revealed that breast cancer subtypes differ not only in primary tumor characteristics but also in their metastatic behavior. In particular, the luminal tumors are remarkable for their significant bone-seeking phenotype; the HER2 subtype demonstrates a significant liver-homing characteristic; whereas so-called triple-negative breast cancers predispose to lung metastases. These findings suggest that this knowledge could potentially be utilized in the development of effective disease surveillance strategies in the pursuit of precision medicine, thus necessitating further investigation.

  2. Molecular markers for tumor cell dissemination in female cancers

    International Nuclear Information System (INIS)

    Obermayr, E.

    2009-01-01

    In the fight against cancer many advances have been made in early detection and treatment of the disease during the last few decades. Nevertheless, many patients still die of cancer due to metastatic spreading of the disease. Tumor cell dissemination may occur very early and usually is not discovered at the time of initial diagnosis. In these cases, the mere excision of the primary tumor is an insufficient treatment. Microscopic tumor residues will remain in the blood, lymph nodes, or the bone marrow and will cause disease recurrence. To improve the patient's prognosis, a sensitive tool for the detection of single tumor cells supplementing conventional diagnostic procedures is required. As the blood is more easily accessible than the bone marrow or tissue biopsies, we intended to identify gene markers for the detection of circulating tumor cells in the blood of cancer patients. We focused on patients with breast, ovarian, endometrial or cervical cancer. Starting from a genome-wide gene expression analysis of tumor cells and blood cells, we found six genes higher expression levels in cancer patients compared to healthy women. These findings suggest that an increased expression of these genes in the blood indicates the presence of circulating tumor cells inducing future metastases and thus the need for adjuvant therapy assisting the primary treatment. Measuring the expression levels of these six genes in the blood may supplement conventional diagnostic tests and improve the patient's prognosis. (author) [de

  3. Genistein and daidzein: different molecular effects on prostate cancer.

    Science.gov (United States)

    Adjakly, Mawussi; Ngollo, Marjolaine; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique

    2013-01-01

    Diet is believed to play an important role in cancer. It has been revealed by epidemiological studies that Asian populations, who consume phytoestrogens in large amounts, have a lower incidence of prostate cancer in comparison with the Western world, where consumption of soy is lower. Genistein and daidzein, the soy phytoestrogens most widely studied, are believed to be potent anticancer agents and have been shown to possess anticancer properties. It has been shown that these compounds inhibit the growth of cancer cells through the modulation of genes controlling cell-cycle progression. Genistein inhibits the activation of the kappa light polypeptide gene enhancer in B-cells (NF-κB), signaling pathway, which is implicated in the balance between cell survival and programmed cell death (apoptosis). Antioxidant and antiangiogenesis properties of genistein have been also described. Soy isoflavones are also implicated in reversion of epigenetic events observed in prostate cancer. Significant advances have been made for understanding how soy isoflavones are implicated in protection against prostate cancer. However, more studies are needed to better-understand and elucidate all pathways mobilized by genistein and daidzein, in order to fully exploit their anticancer properties.

  4. Understanding the Effectiveness of Natural Compound Mixtures in Cancer through Their Molecular Mode of Action

    Directory of Open Access Journals (Sweden)

    Thazin Nwe Aung

    2017-03-01

    Full Text Available Many approaches to cancer management are often ineffective due to adverse reactions, drug resistance, or inadequate target specificity of single anti-cancer agents. In contrast, a combinatorial approach with the application of two or more anti-cancer agents at their respective effective dosages can achieve a synergistic effect that boosts cytotoxicity to cancer cells. In cancer, aberrant apoptotic pathways allow cells that should be killed to survive with genetic abnormalities, leading to cancer progression. Mutations in apoptotic mechanism arising during the treatment of cancer through cancer progression can consequently lead to chemoresistance. Natural compound mixtures that are believed to have multiple specific targets with minimal acceptable side-effects are now of interest to many researchers due to their cytotoxic and chemosensitizing activities. Synergistic interactions within a drug mixture enhance the search for potential molecular targets in cancer cells. Nonetheless, biased/flawed scientific evidence from natural products can suggest false positive therapeutic benefits during drug screening. In this review, we have taken these factors into consideration when discussing the evidence for these compounds and their synergistic therapeutic benefits in cancer. While there is limited evidence for clinical efficacy for these mixtures, in vitro data suggest that these preparations merit further investigation, both in vitro and in vivo.

  5. High-throughput molecular analysis in lung cancer: insights into biology and potential clinical applications.

    Science.gov (United States)

    Ocak, S; Sos, M L; Thomas, R K; Massion, P P

    2009-08-01

    During the last decade, high-throughput technologies including genomic, epigenomic, transcriptomic and proteomic have been applied to further our understanding of the molecular pathogenesis of this heterogeneous disease, and to develop strategies that aim to improve the management of patients with lung cancer. Ultimately, these approaches should lead to sensitive, specific and noninvasive methods for early diagnosis, and facilitate the prediction of response to therapy and outcome, as well as the identification of potential novel therapeutic targets. Genomic studies were the first to move this field forward by providing novel insights into the molecular biology of lung cancer and by generating candidate biomarkers of disease progression. Lung carcinogenesis is driven by genetic and epigenetic alterations that cause aberrant gene function; however, the challenge remains to pinpoint the key regulatory control mechanisms and to distinguish driver from passenger alterations that may have a small but additive effect on cancer development. Epigenetic regulation by DNA methylation and histone modifications modulate chromatin structure and, in turn, either activate or silence gene expression. Proteomic approaches critically complement these molecular studies, as the phenotype of a cancer cell is determined by proteins and cannot be predicted by genomics or transcriptomics alone. The present article focuses on the technological platforms available and some proposed clinical applications. We illustrate herein how the "-omics" have revolutionised our approach to lung cancer biology and hold promise for personalised management of lung cancer.

  6. Molecular genetic study of head and neck cancer

    International Nuclear Information System (INIS)

    Lee, Yong Sik; Shim, Youn Sang; Lee, Je Ho

    1993-01-01

    We analyzed 15 cases of head and neck cancer (13 out of 15 were squqmous cell cancer.) by Southern blotting to identify the possible tumor suppressor gene. Firstly we searched the chromosome 17p with pYNZ22, pMCT35.1 and p144D6. 5 out of 7 informative cases showed loss of heterozygosity implying the loss of tumor suppressor gene near those loci. Afterwards analysis of these 5 cases is needed to identify the presence of tumor suppressor genes and the oncogenetic mechanism. (Author)

  7. Stepwise classification of cancer samples using clinical and molecular data

    Directory of Open Access Journals (Sweden)

    Obulkasim Askar

    2011-10-01

    Full Text Available Abstract Background Combining clinical and molecular data types may potentially improve prediction accuracy of a classifier. However, currently there is a shortage of effective and efficient statistical and bioinformatic tools for true integrative data analysis. Existing integrative classifiers have two main disadvantages: First, coarse combination may lead to subtle contributions of one data type to be overshadowed by more obvious contributions of the other. Second, the need to measure both data types for all patients may be both unpractical and (cost inefficient. Results We introduce a novel classification method, a stepwise classifier, which takes advantage of the distinct classification power of clinical data and high-dimensional molecular data. We apply classification algorithms to two data types independently, starting with the traditional clinical risk factors. We only turn to relatively expensive molecular data when the uncertainty of prediction result from clinical data exceeds a predefined limit. Experimental results show that our approach is adaptive: the proportion of samples that needs to be re-classified using molecular data depends on how much we expect the predictive accuracy to increase when re-classifying those samples. Conclusions Our method renders a more cost-efficient classifier that is at least as good, and sometimes better, than one based on clinical or molecular data alone. Hence our approach is not just a classifier that minimizes a particular loss function. Instead, it aims to be cost-efficient by avoiding molecular tests for a potentially large subgroup of individuals; moreover, for these individuals a test result would be quickly available, which may lead to reduced waiting times (for diagnosis and hence lower the patients distress. Stepwise classification is implemented in R-package stepwiseCM and available at the Bioconductor website.

  8. Classification of biosensor time series using dynamic time warping: applications in screening cancer cells with characteristic biomarkers.

    Science.gov (United States)

    Rai, Shesh N; Trainor, Patrick J; Khosravi, Farhad; Kloecker, Goetz; Panchapakesan, Balaji

    2016-01-01

    The development of biosensors that produce time series data will facilitate improvements in biomedical diagnostics and in personalized medicine. The time series produced by these devices often contains characteristic features arising from biochemical interactions between the sample and the sensor. To use such characteristic features for determining sample class, similarity-based classifiers can be utilized. However, the construction of such classifiers is complicated by the variability in the time domains of such series that renders the traditional distance metrics such as Euclidean distance ineffective in distinguishing between biological variance and time domain variance. The dynamic time warping (DTW) algorithm is a sequence alignment algorithm that can be used to align two or more series to facilitate quantifying similarity. In this article, we evaluated the performance of DTW distance-based similarity classifiers for classifying time series that mimics electrical signals produced by nanotube biosensors. Simulation studies demonstrated the positive performance of such classifiers in discriminating between time series containing characteristic features that are obscured by noise in the intensity and time domains. We then applied a DTW distance-based k -nearest neighbors classifier to distinguish the presence/absence of mesenchymal biomarker in cancer cells in buffy coats in a blinded test. Using a train-test approach, we find that the classifier had high sensitivity (90.9%) and specificity (81.8%) in differentiating between EpCAM-positive MCF7 cells spiked in buffy coats and those in plain buffy coats.

  9. Cancer Chemoprevention by Resveratrol: The p53 Tumor Suppressor Protein as a Promising Molecular Target

    Directory of Open Access Journals (Sweden)

    Danielly C. Ferraz da Costa

    2017-06-01

    Full Text Available Increasing epidemiological and experimental evidence has demonstrated an inverse relationship between the consumption of plant foods and the incidence of chronic diseases, including cancer. Microcomponents that are naturally present in such foods, especially polyphenols, are responsible for the benefits to human health. Resveratrol is a diet-derived cancer chemopreventive agent with high therapeutic potential, as demonstrated by different authors. The aim of this review is to collect and present recent evidence from the literature regarding resveratrol and its effects on cancer prevention, molecular signaling (especially regarding the involvement of p53 protein, and therapeutic perspectives with an emphasis on clinical trial results to date.

  10. Molecular crosstalk between cancer cells and tumor microenvironment components suggests potential targets for new therapeutic approaches in mobile tongue cancer

    International Nuclear Information System (INIS)

    Dayan, Dan; Salo, Tuula; Salo, Sirpa; Nyberg, Pia; Nurmenniemi, Sini; Costea, Daniela Elena; Vered, Marilena

    2012-01-01

    We characterized tumor microenvironment (TME) components of mobile tongue (MT) cancer patients in terms of overall inflammatory infiltrate, focusing on the protumorigenic/anti-inflammatory phenotypes and on cancer-associated fibroblasts (CAFs) in order to determine their interrelations and associations with clinical outcomes. In addition, by culturing tongue carcinoma cells (HSC-3) on a three-dimensional myoma organotypic model that mimics TME, we attempted to investigate the possible existence of a molecular crosstalk between cancer cells and TME components. Analysis of 64 cases of MT cancer patients revealed that the overall density of the inflammatory infiltrate was inversely correlated to the density of CAFs (P = 0.01), but that the cumulative density of the protumorigenic/anti-inflammatory phenotypes, including regulatory T cells (Tregs, Foxp3+), tumor-associated macrophages (TAM2, CD163+), and potentially Tregs-inducing immune cells (CD80+), was directly correlated with the density of CAFs (P = 0.01). The hazard ratio (HR) for recurrence in a TME rich in CD163+ Foxp3+ CD80+ was 2.9 (95% CI 1.03–8.6, P = 0.043 compared with low in CD163+ Foxp3+ CD80+). The HR for recurrence in a TME rich in CAFs was 4.1 (95% confidence interval [CI] 1.3–12.8, P = 0.012 compared with low in CAFs). In vitro studies showed cancer-derived exosomes, epithelial–mesenchymal transition process, fibroblast-to-CAF-like cell transdifferentiation, and reciprocal interrelations between different cytokines suggesting the presence of molecular crosstalk between cancer cells and TME components. Collectively, these results highlighted the emerging need of new therapies targeting this crosstalk between the cancer cells and TME components in MT cancer

  11. Molecular diagnostics detect radio resistant tumor in cancer cervix

    International Nuclear Information System (INIS)

    Nagarajan, B.

    2004-01-01

    After successful external radiation/intracavitary and interstitial radiation therapy some cancer cervix patients presented with recurrent tumors on 6-12 months follow up period. They had high level of IL-6 on first reporting. This augurs well with the premise that up regulation of IL-6 might be involved in tumor progression

  12. Nuclear EGFR as a molecular target in cancer

    International Nuclear Information System (INIS)

    Brand, Toni M.; Iida, Mari; Luthar, Neha; Starr, Megan M.; Huppert, Evan J.; Wheeler, Deric L.

    2013-01-01

    The epidermal growth factor receptor (EGFR) has been one of the most targeted receptors in the field of oncology. While anti-EGFR inhibitors have demonstrated clinical success in specific cancers, most patients demonstrate either intrinsic or acquired resistance within one year of treatment. Many mechanisms of resistance to EGFR inhibitors have been identified, one of these being attributed to alternatively localized EGFR from the cell membrane into the cell’s nucleus. Inside the nucleus, EGFR functions as a co-transcription factor for several genes involved in cell proliferation and angiogenesis, and as a tyrosine kinase to activate and stabilize proliferating cell nuclear antigen and DNA dependent protein kinase. Nuclear localized EGFR is highly associated with disease progression, worse overall survival in numerous cancers, and enhanced resistance to radiation, chemotherapy, and the anti-EGFR therapies gefitinib and cetuximab. In this review the current knowledge of how nuclear EGFR enhances resistance to cancer therapeutics is discussed, in addition to highlighting ways to target nuclear EGFR as an anti-cancer strategy in the future

  13. Cancer stem cell hypotheses: Impact on modern molecular

    Indian Academy of Sciences (India)

    basis for the so-called cancer stem cell (CSC) hypotheses. The first exact proof of CSC ... or less equal ability for tumour regeneration and repopulation. (Nowell 1976 .... Also, there are reports that the 'stemness' (stem-like properties) of brain.

  14. Review Article: Molecular Epidemiology of Breast Cancer: A Review ...

    African Journals Online (AJOL)

    The standard paradigm providing a general mechanistic explanation for the association of cumulative, excessive oestrogen exposure and breast cancer risk is that the proliferative stimulus provided by 17β-estradiol (E2) leads to the appearance of spontaneous mutations. Thus, the key contribution of E2) is the stimulation of ...

  15. Molecular Response to Hypoxia; from C. elegans to cancer

    NARCIS (Netherlands)

    Gort, E.H.

    2008-01-01

    Oncogenesis is governed by genetic and epigenetic events that co-opt to malignant progression. The role of the microenvironment in tumorigenesis and maintenance is increasingly appreciated. Oxygen supply is one of the rate limiting microenvironmental factors. Like healthy cells, cancer cells rely on

  16. A review of molecular biomarkers for bladder cancer

    African Journals Online (AJOL)

    McRoy

    Volume 2 Issue 3 September – December 2013 ... methodology were identified but only half of them have shown consistence ... Conclusion: It is envisaged that a combination ... biomarkers for bladder cancer are adopted in the UK standard practice. ... words used for the literature review were ..... Multi centre validation.

  17. Molecular Subtypes and Clinical Outcomes of Breast Cancer

    African Journals Online (AJOL)

    2010-01-04

    Jan 4, 2010 ... Some early work has started in earnest at both the. AKUH(N) and Kijabe Hospitals to try and stratify our breast cancer patients to those mentioned subtypes to help in both diagnosis and treatment. The limiting fac- tors are small numbers of patients expense to undertake the tests and lack of both internal ...

  18. Molecular Determinants of Hormone-Refractory Prostate Cancer

    Science.gov (United States)

    2015-07-01

    Suzuki Y, Honda G, et al. Large-scale identification and characterization of human genes that activate NF- kappaB and MAPK signaling pathways. Oncogene...2003 May 22;22(21):3307-18. Mendiratta P, et al. Genomic strategy for targeting therapy in castration-resistant prostate cancer. J Clin Oncol. 2009 Apr

  19. Clinical and molecular characterization of BRCA-associated breast cancer

    DEFF Research Database (Denmark)

    Soenderstrup, I. M.H.; Laenkholm, A. V.; Jensen, M. B.

    2018-01-01

    Background: In breast cancer (BC) patients a cancer predisposing BRCA1/2 mutation is associated with adverse tumor characteristics, risk assessment and treatment allocation. We aimed to estimate overall- (OS) and disease-free survival (DFS) according to tumor characteristics and treatment among...... women who within two years of definitive surgery for primary BC were shown to carry a mutation in BRCA1/2 . Material and methods: From the clinical database of the Danish Breast Cancer Group we included 141 BRCA1 and 96 BRCA2 BC patients. Estrogen receptor and HER2 status were centrally reviewed......–81). Ten-year OS and DFS for BRCA2 BC were 88% (95% CI 78–94) and 84% (95% CI 74–91). BRCA1 BC patients as compared to BRCA2 BC patients had a higher risk of BC relapse or non-breast cancer within ten years of follow-up, independent of ER status (adjusted HR 2.78 95% CI 1.28–6.05, p = .01), but BRCA...

  20. Cell-of-Origin Patterns Dominate the Molecular Classification of 10,000 Tumors from 33 Types of Cancer

    NARCIS (Netherlands)

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

    2018-01-01

    We conducted comprehensive integrative molecular analyses of the complete set of tumors in The Cancer Genome Atlas (TCGA), consisting of approximately 10,000 specimens and representing 33 types of cancer. We performed molecular clustering using data on chromosome-arm-level aneuploidy, DNA

  1. Next Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

    Science.gov (United States)

    2016-07-01

    AWARD NUMBER: W81XWH- 14-1-0192 TITLE: Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer...DATES COVERED 4. TITLE AND SUBTITLE Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue

  2. Prognostic and predictive potential molecular biomarkers in colon cancer.

    Science.gov (United States)

    Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

    2011-01-01

    An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

  3. Molecular Effects of Doxorubicin on Choline Metabolism in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Menglin Cheng

    2017-08-01

    Full Text Available Abnormal choline phospholipid metabolism is a hallmark of cancer. The magnetic resonance spectroscopy (MRS detected total choline (tCho signal can serve as an early noninvasive imaging biomarker of chemotherapy response in breast cancer. We have quantified the individual components of the tCho signal, glycerophosphocholine (GPC, phosphocholine (PC and free choline (Cho, before and after treatment with the commonly used chemotherapeutic drug doxorubicin in weakly metastatic human MCF7 and triple-negative human MDA-MB-231 breast cancer cells. While the tCho concentration did not change following doxorubicin treatment, GPC significantly increased and PC decreased. Of the two phosphatidylcholine-specific PLD enzymes, only PLD1, but not PLD2, mRNA was down-regulated by doxorubicin treatment. For the two reported genes encoding GPC phosphodiesterase, the mRNA of GDPD6, but not GDPD5, decreased following doxorubicin treatment. mRNA levels of choline kinase α (ChKα, which converts Cho to PC, were reduced following doxorubicin treatment. PLD1 and ChKα protein levels decreased following doxorubicin treatment in a concentration dependent manner. Treatment with the PLD1 specific inhibitor VU0155069 sensitized MCF7 and MDA-MB-231 breast cancer cells to doxorubicin-induced cytotoxicity. Low concentrations of 100 nM of doxorubicin increased MDA-MB-231 cell migration. GDPD6, but not PLD1 or ChKα, silencing by siRNA abolished doxorubicin-induced breast cancer cell migration. Doxorubicin induced GPC increase and PC decrease are caused by reductions in PLD1, GDPD6, and ChKα mRNA and protein expression. We have shown that silencing or inhibiting these genes/proteins can promote drug effectiveness and reduce adverse drug effects. Our findings emphasize the importance of detecting PC and GPC individually.

  4. The development of epidermal growth factor receptor molecular imaging in cancer

    International Nuclear Information System (INIS)

    Zhou Xiaoliang; Wang Hao; Shi Peiji; Liu Jianfeng; Meng Aimin

    2013-01-01

    In vivo epidermal growth factor receptor (EGFR) targeted therapy has great potential for cancer diagnosis and the evaluation of curative effects. Enhancement of EGFR-targeted therapy needs a reliable quantitative molecular imaging method which could enable monitoring of receptor drug binding and receptor occupancy in vivo, and identification of the mutation in EGFR. PET or SPECT is the most advanced molecular imaging technology of non-invasively selecting responders, predicting therapeutic outcome and monitoring EGFR-targeted treatment. This review analyzed the present situation and research progress of molecular imaging agents. (authors)

  5. Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective

    Directory of Open Access Journals (Sweden)

    Guoli Chen

    2016-01-01

    Full Text Available Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional “one test-one drug” assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC.

  6. Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective.

    Science.gov (United States)

    Chen, Guoli; Yang, Zhaohai; Eshleman, James R; Netto, George J; Lin, Ming-Tseh

    2016-01-01

    Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional "one test-one drug" assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC.

  7. A reductionist approach to extract robust molecular markers from microarray data series - Isolating markers to track osseointegration.

    Science.gov (United States)

    Barik, Anwesha; Banerjee, Satarupa; Dhara, Santanu; Chakravorty, Nishant

    2017-04-01

    Complexities in the full genome expression studies hinder the extraction of tracker genes to analyze the course of biological events. In this study, we demonstrate the applications of supervised machine learning methods to reduce the irrelevance in microarray data series and thereby extract robust molecular markers to track biological processes. The methodology has been illustrated by analyzing whole genome expression studies on bone-implant integration (ossointegration). Being a biological process, osseointegration is known to leave a trail of genetic footprint during the course. In spite of existence of enormous amount of raw data in public repositories, researchers still do not have access to a panel of genes that can definitively track osseointegration. The results from our study revealed panels comprising of matrix metalloproteinases and collagen genes were able to track osseointegration on implant surfaces (MMP9 and COL1A2 on micro-textured; MMP12 and COL6A3 on superimposed nano-textured surfaces) with 100% classification accuracy, specificity and sensitivity. Further, our analysis showed the importance of the progression of the duration in establishment of the mechanical connection at bone-implant surface. The findings from this study are expected to be useful to researchers investigating osseointegration of novel implant materials especially at the early stage. The methodology demonstrated can be easily adapted by scientists in different fields to analyze large databases for other biological processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Understanding binding affinity : A combined isothermal titration calorimetry/molecular dynamics study of the binding of a series of hydrophobically modified benzamidinium chloride inhibitors to trypsin

    NARCIS (Netherlands)

    Talhout, Reinskje; Villa, Alessandra; Mark, AE; Engberts, JBFN

    2003-01-01

    The binding of a series of p-alkylbenzamidinium chloride inhibitors to the serine proteinase trypsin over a range of temperatures has been studied using isothermal titration (micro)calorimetry and molecular dynamics simulation techniques. The inhibitors have small structural variations at the para

  9. Discretization of Gene Expression Data Unmasks Molecular Subgroups Recurring in Different Human Cancer Types.

    Directory of Open Access Journals (Sweden)

    Manfred Beleut

    Full Text Available Despite the individually different molecular alterations in tumors, the malignancy associated biological traits are strikingly similar. Results of a previous study using renal cell carcinoma (RCC as a model pointed towards cancer-related features, which could be visualized as three groups by microarray based gene expression analysis. In this study, we used a mathematic model to verify the presence of these groups in RCC as well as in other cancer types. We developed an algorithm for gene-expression deviation profiling for analyzing gene expression data of a total of 8397 patients with 13 different cancer types and normal tissues. We revealed three common Cancer Transcriptomic Profiles (CTPs which recurred in all investigated tumors. Additionally, CTPs remained robust regardless of the functions or numbers of genes analyzed. CTPs may represent common genetic fingerprints, which potentially reflect the closely related biological traits of human cancers.

  10. Molecular Pathways: Cachexia Signaling-A Targeted Approach to Cancer Treatment.

    Science.gov (United States)

    Miyamoto, Yuji; Hanna, Diana L; Zhang, Wu; Baba, Hideo; Lenz, Heinz-Josef

    2016-08-15

    Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively affects quality of life and portends a poor prognosis. Numerous molecular substrates and mechanisms underlie the dysregulation of skeletal muscle synthesis and degradation observed in cancer cachexia, including proinflammatory cytokines (TNFα, IL1, and IL6), and the NF-κB, IGF1/AKT/mTOR, and myostatin/activin-SMAD pathways. Recent preclinical and clinical studies have demonstrated that anti-cachexia drugs (such as MABp1 and soluble receptor antagonist of myostatin/activin) not only prevent muscle wasting but also may prolong overall survival. In this review, we focus on the significance of cachexia signaling in patients with cancer and highlight promising drugs targeting tumor cachexia in clinical development. Clin Cancer Res; 22(16); 3999-4004. ©2016 AACR. ©2016 American Association for Cancer Research.

  11. Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.

    Science.gov (United States)

    Celià-Terrassa, Toni

    2018-05-04

    Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.

  12. 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...

  13. Epidemiological-molecular evidence of metabolic reprogramming on proliferation, autophagy and cell signaling in pancreas cancer.

    Science.gov (United States)

    Søreide, Kjetil; Sund, Malin

    2015-01-28

    Pancreatic cancer remains one of the deadliest human cancers with little progress made in survival over the past decades, and 5-year survival usually below 5%. Despite this dismal scenario, progresses have been made in understanding of the underlying tumor biology through among other definition of precursor lesions, delineation of molecular pathways, and advances in genome-wide technology. Further, exploring the relationship between epidemiological risk factors involving metabolic features to that of an altered cancer metabolism may provide the foundation for new therapies. Here we explore how nutrients and caloric intake may influence the KRAS-driven ductal carcinogenesis through mediators of metabolic stress, including autophagy in presence of TP53, advanced glycation end products (AGE) and the receptors (RAGE) and ligands (HMGB1), as well as glutamine pathways, among others. Effective understanding the cancer metabolism mechanisms in pancreatic cancer may propose new ways of prevention and treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. Genomic and Molecular Landscape of DNA Damage Repair Deficiency across The Cancer Genome Atlas

    Directory of Open Access Journals (Sweden)

    Theo A. Knijnenburg

    2018-04-01

    Full Text Available Summary: DNA damage repair (DDR pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structure-based analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data allowed us to identify alterations that phenocopy deleterious TP53 mutations. These frequent DDR gene alterations in many human cancers have functional consequences that may determine cancer progression and guide therapy. : Knijnenburg et al. present The Cancer Genome Atlas (TCGA Pan-Cancer analysis of DNA damage repair (DDR deficiency in cancer. They use integrative genomic and molecular analyses to identify frequent DDR alterations across 33 cancer types, correlate gene- and pathway-level alterations with genome-wide measures of genome instability and impaired function, and demonstrate the prognostic utility of DDR deficiency scores. Keywords: The Cancer Genome Atlas PanCanAtlas project, DNA damage repair, somatic mutations, somatic copy-number alterations, epigenetic silencing, DNA damage footprints, mutational signatures, integrative statistical analysis, protein structure analysis

  15. The promise of molecular epidemiology in defining the association between radiation and cancer

    International Nuclear Information System (INIS)

    Neta, R.

    2000-01-01

    Molecular epidemiology involves the inclusion in epidemiologic studies of biologic measurements made at a genetic and molecular level and aims to improve the current knowledge of disease etiology and risk. One of the goals of molecular epidemiology studies of cancer is to determine the role of environmental and genetic factors in initiation and progression of malignancies and to use this knowledge to develop preventive strategies. This approach promises extraordinary opportunities for revolutionizing the practice of medicine and reducing risk. However, this will be accompanied by the need to address and resolve many challenges, such as ensuring the appropriate interpretation of molecular testing and resolving associated ethical, legal, and social issues. Traditional epidemiologic approaches determined that exposure to ionizing radiation poses significantly increased risk of leukemia and several other types of cancer. Such studies provided the basis for setting exposure standards to protect the public and the workforce from potentially adverse effects of ionizing radiation. These standards were set by using modeling approaches to extrapolate from the biological effects observed in high-dose radiation studies to predicted, but mostly immeasurable, effects at low radiation doses. It is anticipated that the addition of the molecular parameters to the population-based studies will help identify the genes and pathways characteristic of cancers due to radiation exposure of individuals, as well as identify susceptible or resistant subpopulations. In turn, the information about the molecular mechanisms should aid to improve risk assessment. While studies on radiogenic concerns are currently limited to only a few candidate genes, the exponential growth of scientific knowledge and technology promises expansion of knowledge about identity of participating genes and pathways in the future. This article is meant to provide an introductory overview of recent advances in

  16. Theragnosis-based combined cancer therapy using doxorubicin-conjugated microRNA-221 molecular beacon.

    Science.gov (United States)

    Lee, Jonghwan; Choi, Kyung-Ju; Moon, Sung Ung; Kim, Soonhag

    2016-01-01

    Recently, microRNA (miRNA or miR) has emerged as a new cancer biomarker because of its high expression level in various cancer types and its role in the control of tumor suppressor genes. In cancer studies, molecular imaging and treatment based on target cancer markers have been combined to facilitate simultaneous cancer diagnosis and therapy. In this study, for combined therapy with diagnosis of cancer, we developed a doxorubicin-conjugated miR-221 molecular beacon (miR-221 DOXO MB) in a single platform composed of three different nucleotides: miR-221 binding sequence, black hole quencher 1 (BHQ1), and doxorubicin binding site. Imaging of endogenous miR-221 was achieved by specific hybridization between miR-221 and the miR-221 binding site in miR-221 DOXO MB. The presence of miR-221 triggered detachment of the quencher oligo and subsequent activation of a fluorescent signal of miR-221 DOXO MB. Simultaneous cancer therapy in C6 astrocytoma cells and nude mice was achieved by inhibition of miRNA-221 function that downregulates tumor suppressor genes. The detection of miR-221 expression and inhibition of miR-221 function by miR-221 DOXO MB provide the feasibility as a cancer theragnostic probe. Furthermore, a cytotoxic effect was induced by unloading of doxorubicin intercalated into miR-221 DOXO MB inside cells. Loss of miR-221 function and cytotoxicity induced by the miR-221 DOXO MB provides combined therapeutic efficacy against cancers. This method could be used as a new theragnostic probe with enhanced therapy to detect and inhibit many cancer-related miRNAs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. [Establishing Individualized Medicine for Intractable Cancer Based on Clinical Molecular Pathogenesis].

    Science.gov (United States)

    Jono, Hirofumi

    2018-01-01

     Although cancer treatment has dramatically improved with the development of molecular-targeted agents over the past decade, identifying eligible patients and predicting the therapeutic effects remain a major challenge. Because intratumoral heterogeneity represents genetic and molecular differences affecting patients' responses to these therapeutic agents, establishing individualized medicine based on precise molecular pathological analysis of tumors is urgently required. This review focuses on the pathogenesis of oral squamous cell carcinoma (OSCC), a common head and neck neoplasm, and introduces our approaches toward developing novel anticancer therapies particularly based on clinical molecular pathogenesis. Deeper understanding of more precise molecular pathogenesis in clinical settings may open up novel strategies for establishing individualized medicine for OSCC.

  18. 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.

  19. Synchronous primary ovarian and endometrial cancers: a series of cases and a review of literature

    Directory of Open Access Journals (Sweden)

    Sylwia Dębska-Szmich

    2014-03-01

    Full Text Available Synchronous cancers account for 0.7-1.8% of all gynecologic cancers. Among them, synchronous ovarian and endometrial cancers are predominant (40-53%. Patients with synchronous cancers have better prognosis than those with single disseminated cancer. We present 10 patients with synchronous ovarian and endometrial cancers who were treated at the Chemotherapy Department of the Medical University of Lodz in 2009-2013. The most often reported symptom of the disease was abnormal vaginal bleeding (6 patients. The range of the patients’ age was 48-62 and the median age was 56. Five patients had stage I of ovarian cancer, single patients had stage IIA, IIB and IIIB, 2 patients had stage IIIC. Three patients had I, 5 – II, and 2 – III stage of endometrial cancer. All patients had endometrioid type of endometrial cancer, 7 of them had also the same histological type of ovarian cancer. All patients had adjuvant chemotherapy because of ovarian cancer, none of them had adjuvant radiotherapy. One patient was lost to follow up. For other patients a median follow up was 13 months (range: 3-53 months. One patient experienced relapse, all patients are alive. Synchronous ovarian and endometrial cancers are usually diagnosed at an earlier stage, have lower histological grade and better prognosis than single cancers. The most common histological type of both endometrial and ovarian cancers is endometrioid carcinoma. The first symptoms reported by our patients and the course of the disease were concordant with data from the literature.

  20. Phosphoproteomic analysis for the identification of predictive molecular factors and new molecular targets in breast, colorectal, ovary, and lung cancer

    International Nuclear Information System (INIS)

    Belluco, C.; De Paoli, P.

    2009-01-01

    Neoadjuvant chemotherapy is a standard therapeutic approach for several types of locally advanced and metastatic tumors. Molecular factors predictive of response to therapy are highly needed for exploiting the potential benefit of properative chemotherapy. Moreover, neoadjuvant chemotherapy represents an ideal clinical model for studying predictive factors since it allows to obtain pre-treatment tissue biopsies which can be analyzed and the results compared to clinical and pathological response. Protein kinases represent some of the most important drug targets in medicine today and their aberrant activation are involved in many disease processes including cancer development and progression

  1. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, J. F.; van der Wall, Elsken; Mali, Willem P Th M; Derksen, Patrick W B; van Diest, Paul J; van Bergen En Henegouwen, Paul M P

    PURPOSE: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. PROCEDURES: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  2. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, Jeroen F.; van der Wall, Elsken; Mali, W.P.T.M.; Derksen, Patrick W B; van Diest, Paul J.; van Bergen En Henegouwen, Paul M P

    Purpose: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. Procedures: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  3. Identification of circulating prostate cancer cells: A challenge to the clinical implementation of molecular biology (Review)

    NARCIS (Netherlands)

    Schamhart, Denis H. J.; Maiazza, Ruth; Kurth, Karl-Heinz

    2005-01-01

    Conventional diagnosis of prostate cancer does not appear to be sensitive enough to differentiate pre-operatively between organ-confined and extracapsular disease. New technologies. arising from the field of molecular biology, have been introduced to improve diagnosis and their implementation into

  4. Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis

    Science.gov (United States)

    Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

    2016-01-01

    This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine. PMID:28078184

  5. MOLECULAR MARKERS OF BLADDER CANCER: FROM THE PARTICULAR TO THE GENERAL

    Directory of Open Access Journals (Sweden)

    A. A. Zabolotneva

    2014-08-01

    Full Text Available Bladder cancer (BC is the second most common urinary tract malignancy. Early diagnosis of BC generally increases the probability of successful treatment in a patient. The paper considers noninvasive diagnosis methods for BC and gives a database of the known molecular markers of this disease.

  6. 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.

  7. QUANTITATION OF MOLECULAR ENDPOINTS FOR THE DOSE-RESPONSE COMPONENT OF CANCER RISK ASSESSMENT

    Science.gov (United States)

    Cancer risk assessment involves the steps of hazard identification, dose-response assessment, exposure assessment and risk characterization. The rapid advances in the use of molecular biology approaches has had an impact on all four components, but the greatest overall current...

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

    Science.gov (United States)

    Reinhold, William C

    2015-12-10

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

  9. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer

    NARCIS (Netherlands)

    Wang, Kai; Yuen, Siu Tsan; Xu, Jiangchun; Lee, Siu Po; Yan, Helen H N; Shi, Stephanie T; Siu, Hoi Cheong; Deng, Shibing; Chu, Kent Man; Law, Simon; Chan, Kok Hoe; Chan, Annie S Y; Tsui, Wai Yin; Ho, Siu Lun; Chan, Anthony K W; Man, Jonathan L K; Foglizzo, Valentina; Ng, Man Kin; Chan, April S; Ching, Yick Pang; Cheng, Grace H W; Xie, Tao; Fernandez, Julio; Li, Vivian S W; Clevers, Hans; Rejto, Paul A; Mao, Mao; Leung, Suet Yi

    Gastric cancer is a heterogeneous disease with diverse molecular and histological subtypes. We performed whole-genome sequencing in 100 tumor-normal pairs, along with DNA copy number, gene expression and methylation profiling, for integrative genomic analysis. We found subtype-specific genetic and

  10. Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis.

    Science.gov (United States)

    Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

    2016-01-01

    This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine.

  11. Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer

    Czech Academy of Sciences Publication Activity Database

    Polášek, Miloslav; Yang, Y.; Schühle, D. T.; Yaseen, M. A.; Kim, Y. R.; Sung, Y. S.; Guimaraes, A. R.; Caravan, P.

    2017-01-01

    Roč. 7, Aug 14 (2017), č. článku 8114. ISSN 2045-2322 Institutional support: RVO:61388963 Keywords : fibrosis * molecular imaging * pancreatic cancer Subject RIV: FD - Oncology ; Hematology OBOR OECD: Oncology Impact factor: 4.259, year: 2016 https://www.nature.com/ articles /s41598-017-08838-6

  12. Advanced Lung Cancer Screening: An Individualized Molecular Nanotechnology Approach

    Science.gov (United States)

    2016-03-01

    proportion of smokers , former 146 smokers and never smokers was not different between cases and controls. 147 Detection of DNA Methylation 148 We...highest risk smokers for an expensive screening modality such as CT scanning. Hypothesis: DNA methylation testing is more specific in selecting those...with non -cancerous nodules, and have completed the writing of a manuscript containing these results. The abstract of that manuscript is as follows

  13. Training Program in the Molecular Basis of Breast Cancer Research

    Science.gov (United States)

    1996-10-01

    the pathogenesis of these cancers. In concert decidua were immunostained with an anti-BrdU monoclonal with Knudson’s "two- hit " theory of...12618-12622ical homogeneity from bovine testes. The high level of DNA 32. Higashitani, A., Tabata , S., Endo, H., and Hotta, Y. (1990) Cell Struct. Funct...separate enzymes. J. Biol. Chem. 250:8438-8444. 21. Higashitani, A., S. Tabata , H. Endo, and Y. Hotta. 1990. Purification of DNA 51. Stubbs, L., and H

  14. Tryptophan metabolism in breast cancers: molecular imaging and immunohistochemistry studies

    International Nuclear Information System (INIS)

    Juhász, Csaba; Nahleh, Zeina; Zitron, Ian; Chugani, Diane C.; Janabi, Majid Z.; Bandyopadhyay, Sudeshna; Ali-Fehmi, Rouba; Mangner, Thomas J.; Chakraborty, Pulak K.; Mittal, Sandeep; Muzik, Otto

    2012-01-01

    Introduction: Tryptophan oxidation via the kynurenine pathway is an important mechanism of tumoral immunoresistance. Increased tryptophan metabolism via the serotonin pathway has been linked to malignant progression in breast cancer. In this study, we combined quantitative positron emission tomography (PET) with tumor immunohistochemistry to analyze tryptophan transport and metabolism in breast cancer. Methods: Dynamic α-[ 11 C]methyl-L-tryptophan (AMT) PET was performed in nine women with stage II–IV breast cancer. PET tracer kinetic modeling was performed in all tumors. Expression of L-type amino acid transporter 1 (LAT1), indoleamine 2,3-dioxygenase (IDO; the initial and rate-limiting enzyme of the kynurenine pathway) and tryptophan hydroxylase 1 (TPH1; the initial enzyme of the serotonin pathway) was assessed by immunostaining of resected tumor specimens. Results: Tumor AMT uptake peaked at 5–20 min postinjection in seven tumors; the other two cases showed protracted tracer accumulation. Tumor standardized uptake values (SUVs) varied widely (2.6–9.8) and showed a strong positive correlation with volume of distribution values derived from kinetic analysis (P < .01). Invasive ductal carcinomas (n = 6) showed particularly high AMT SUVs (range, 4.7–9.8). Moderate to strong immunostaining for LAT1, IDO and TPH1 was detected in most tumor cells. Conclusions: Breast cancers show differential tryptophan kinetics on dynamic PET. SUVs measured 5–20 min postinjection reflect reasonably the tracer's volume of distribution. Further studies are warranted to determine if in vivo AMT accumulation in these tumors is related to tryptophan metabolism via the kynurenine and serotonin pathways.

  15. 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.

  16. Molecular Basis of Alcohol-Related Gastric and Colon Cancer.

    Science.gov (United States)

    Na, Hye-Kyung; Lee, Ja Young

    2017-05-24

    Many meta-analysis, large cohort studies, and experimental studies suggest that chronic alcohol consumption increases the risk of gastric and colon cancer. Ethanol is metabolized by alcohol dehydrogenases (ADH), catalase or cytochrome P450 2E1 (CYP2E1) to acetaldehyde, which is then further oxidized to acetate by aldehyde dehydrogenase (ALDH). Acetaldehyde has been classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen to humans. The acetaldehyde level in the stomach and colon is locally influenced by gastric colonization by Helicobacter pylori or colonic microbes, as well as polymorphisms in the genes encoding tissue alcohol metabolizing enzymes, especially ALDH2. Alcohol stimulates the uptake of carcinogens and their metabolism and also changes the composition of enteric microbes in a way to enhance the aldehyde level. Alcohol also undergoes chemical coupling to membrane phospholipids and disrupts organization of tight junctions, leading to nuclear translocation of β-catenin and ZONAB, which may contributes to regulation of genes involved in proliferation, invasion and metastasis. Alcohol also generates reactive oxygen species (ROS) by suppressing the expression of antioxidant and cytoprotective enzymes and inducing expression of CYP2E1 which contribute to the metabolic activation of chemical carcinogens. Besides exerting genotoxic effects by directly damaging DNA, ROS can activates signaling molecules involved in inflammation, metastasis and angiogenesis. In addition, alcohol consumption induces folate deficiency, which may result in aberrant DNA methylation profiles, thereby influencing cancer-related gene expression.

  17. Application of tissue mesodissection to molecular cancer diagnostics.

    Science.gov (United States)

    Krizman, David; Adey, Nils; Parry, Robert

    2015-02-01

    To demonstrate clinical application of a mesodissection platform that was developed to combine advantages of laser-based instrumentation with the speed/ease of manual dissection for automated dissection of tissue off standard glass slides. Genomic analysis for KRAS gene mutation was performed on formalin fixed paraffin embedded (FFPE) cancer patient tissue that was dissected using the mesodissection platform. Selected reaction monitoring proteomic analysis for quantitative Her2 protein expression was performed on FFPE patient tumour tissue dissected by a laser-based instrument and the MilliSect instrument. Genomic analysis demonstrates highly confident detection of KRAS mutation specifically in lung cancer cells and not the surrounding benign, non-tumour tissue. Proteomic analysis demonstrates Her2 quantitative protein expression in breast cancer cells dissected manually, by laser-based instrumentation and by MilliSect instrumentation (mesodissection). Slide-mounted tissue dissection is commonly performed using laser-based instruments or manually scraping tissue by scalpel. Here we demonstrate that the mesodissection platform as performed by the MilliSect instrument for tissue dissection is cost-effective; it functions comparably to laser-based dissection and which can be adopted into a clinical diagnostic workflow. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  18. Quantum Interactomics and Cancer Molecular Mechanisms: I. Report Outline

    CERN Document Server

    Baianu, I C

    2004-01-01

    Single cell interactomics in simpler organisms, as well as somatic cell interactomics in multicellular organisms, involve biomolecular interactions in complex signalling pathways that were recently represented in modular terms by quantum automata with ‘reversible behavior’ representing normal cell cycling and division. Other implications of such quantum automata, modular modeling of signaling pathways and cell differentiation during development are in the fields of neural plasticity and brain development leading to quantum-weave dynamic patterns and specific molecular processes underlying extensive memory, learning, anticipation mechanisms and the emergence of human consciousness during the early brain development in children. Cell interactomics is here represented for the first time as a mixture of ‘classical’ states that determine molecular dynamics subject to Boltzmann statistics and ‘steady-state’, metabolic (multi-stable) manifolds, together with ‘configuration’ spaces of metastable quant...

  19. Current and future molecular diagnostics in colorectal cancer and colorectal adenoma.

    Science.gov (United States)

    Tsang, Andy Hin-Fung; Cheng, Ka-Ho; Wong, Apple Siu-Ping; Ng, Simon Siu-Man; Ma, Brigette Buig-Yue; Chan, Charles Ming-Lok; Tsui, Nancy Bo-Yin; Chan, Lawrence Wing-Chi; Yung, Benjamin Yat-Ming; Wong, Sze-Chuen Cesar

    2014-04-14

    Colorectal cancer (CRC) is one of the most prevalent cancers in developed countries. On the other hand, CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy. Since CRC develops slowly from precancerous lesions, early detection can reduce both the incidence and mortality of the disease. Fecal occult blood test is a widely used non-invasive screening tool for CRC. Although fecal occult blood test is simple and cost-effective in screening CRC, there is room for improvement in terms of the accuracy of the test. Genetic dysregulations have been found to play an important role in CRC development. With better understanding of the molecular basis of CRC, there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC. In this review, the molecular basis of CRC development, the characteristics and applications of different non-invasive molecular biomarkers, as well as the technologies available for the detection were discussed. This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state, colorectal adenoma.

  20. Prostate cancer molecular profiling: the Achilles heel for the implementation of precision medicine.

    Science.gov (United States)

    Oliveira-Barros, Eliane Gouvêa; Nicolau-Neto, Pedro; Da Costa, Nathalia Meireles; Pinto, Luís Felipe Ribeiro; Palumbo, Antonio; Nasciutti, Luiz Eurico

    2017-11-01

    Cancer has been mainly treated by traditional therapeutic approaches which do not consider the human genetic diversity and present limitations, probably as a consequence of a poor knowledge of both patient's genetic background and tumor biology. Due to genome project conclusion and large-scale gene analyses emergence, the therapeutic management of several prevalent and aggressive tumors has dramatically improved and represents the closest examples of a precision medicine intervention in this field. Nonetheless, prostate cancer (PCa) remains as a challenge to personalized medicine implementation, probably due to its notorious heterogeneous molecular profile. Cancer treatment personalized approaches rely on the premise that a well-defined panorama of tumor molecular alterations can help selecting new and specific therapeutic targets for its treatment and potentially discriminate tumors which behave differentially. Lately, molecular and genetic studies have been investigating PCa basis, revealing multiple recurrent genomic alterations that include mutations, DNA copy-number variations, rearrangements, and gene fusions, among others. In addition to the increment on PCa molecular biology knowledge, mapping the molecular alterations pattern of this neoplasia, especially the differences existent between tumors displaying distinct behaviors, could represent a great improvement concerning the identification of new targets, personalized medicine, and patients' management and prognosis. © 2017 International Federation for Cell Biology.

  1. Molecular Innovations Toward Theranostics of Aggressive Prostate Cancer

    Science.gov (United States)

    2017-11-01

    PET/ MRI systems in diagnostic radiology, our molecular design of dual-modality agents possessing a “single pharmacological behavior” offers a...for magnetic resonance imaging ( MRI ), microbubbles for ultrasound imaging (US), radioisotopes for positron emission tomography (PET) and single...feature depicted here is represented by a PAMAM−DTPA (Gd) system (G0−G9) that was developed for MRI contrast agents. Different dendrimer systems may

  2. Baseline staging tests based on molecular subtype is necessary for newly diagnosed breast cancer.

    Science.gov (United States)

    Chen, Xuesong; Sun, Lichun; Cong, Yingying; Zhang, Tingting; Lin, Qiushi; Meng, Qingwei; Pang, Hui; Zhao, Yanbin; Li, Yu; Cai, Li; Dong, Xiaoqun

    2014-03-17

    Bone scanning (BS), liver ultrasonography (LUS), and chest radiography (CXR) are commonly recommended for baseline staging in patients with newly diagnosed breast cancer. The purpose of this study is to demonstrate whether these tests are indicated for specific patient subpopulation based on clinical staging and molecular subtype. A retrospective study on 5406 patients with newly diagnosed breast cancer was conducted to identify differences in occurrence of metastasis based on clinical staging and molecular subtypes. All patients had been evaluated by BS, LUS and CXR at diagnosis. Complete information on clinical staging was available in 5184 patients. For stage I, II, and III, bone metastasis rate was 0%, 0.6% and 2.7%, respectively (P diagnosed breast cancer.

  3. Progress in Molecular Imaging in Endoscopy and Endomicroscopy for Cancer Imaging

    Directory of Open Access Journals (Sweden)

    Supang Khondee

    2013-01-01

    Full Text Available Imaging is an essential tool for effective cancer management. Endoscopes are important medical instruments for performing in vivo imaging in hollow organs. Early detection of cancer can be achieved with surveillance using endoscopy, and has been shown to reduce mortality and to improve outcomes. Recently, great advancements have been made in endoscopic instruments, including new developments in optical designs, light sources, optical fibers, miniature scanners, and multimodal systems, allowing for improved resolution, greater tissue penetration, and multispectral imaging. In addition, progress has been made in the development of highly-specific optical probes, allowing for improved specificity for molecular targets. Integration of these new endoscopic instruments with molecular probes provides a unique opportunity for significantly improving patient outcomes and has potential to further improve early detection, image guided therapy, targeted therapy, and personalized medicine. This work summarizes current and evolving endoscopic technologies, and provides an overview of various promising optical molecular probes.

  4. СD44+/CD24- markers of cancer stem cells in patients with breast cancer of different molecular subtypes.

    Science.gov (United States)

    Chekhun, S V; Zadvorny, T V; Tymovska, Yu O; Anikusko, M F; Novak, O E; Polishchuk, L Z

    2015-03-01

    To determine frequency of tumors with immunohistochemical markers of cancer stem cells (CSC) CD44+/CD24- in patients with breast cancer (BC) of different molecular subtype and to evaluate their prognostic value. Surgical material of 132 patients with BC stage I-II, age from 23 to 75 years, mean age - 50.2 ± 3.1 years was studied. Clinical, immunohistochemical (expression CD44+/CD24-), morphological, statistical. BC is characterized by heterogeneity of molecular subtypes and expression of markers (CD44+/CD24-). Immunohistochemical study of expression of CSC markers in surgical material has detected their expression in 34 (25.4%) patients with BC of different molecular subtypes. The highest frequency of cells with expression of CSC marker was observed in patients with basal molecular subtype (44.8% patients). Most of BC patients with phenotype CD44+/CD24 had stage I of tumor process (34.3%). Statistical processing of data has showen that Yule colligation coefficient equaled 0.28 (р > 0.05) that argues poor correlation between stage of tumor process and number of tumors with positive expression of CSC markers. Statistical processing of data has showen high correlation between presence of cells with expression of CSC markers and metastases of BC in regional lymph nodes (Yule colligation coefficient equals 0.943; р molecular subtype depending on expression of CSC CD44+/CD24- markers was detected. Survival of patients with basal BC was reliably higher at lack in tumors of cells with CSC markers CD44+/CD24- and, correspondingly, lower at presence of such cells (р markers was not determined (р > 0.05). Significance of tumor cells with markers CD44+/CD24- within the limits of molecular subtype of BC may be additional criterion for advanced biological characteristic of BC, and in patients with BC of basal molecular subtype - for predictive evaluation of individual potential of tumor to aggressive clinical course.

  5. Multiple Molecular and Cellular Mechanisms of Action of Lycopene in Cancer Inhibition

    Directory of Open Access Journals (Sweden)

    Cristina Trejo-Solís

    2013-01-01

    Full Text Available Epidemiological studies suggest that including fruits, vegetables, and whole grains in regular dietary intake might prevent and reverse cellular carcinogenesis, reducing the incidence of primary tumours. Bioactive components present in food can simultaneously modulate more than one carcinogenic process, including cancer metabolism, hormonal balance, transcriptional activity, cell-cycle control, apoptosis, inflammation, angiogenesis and metastasis. Some studies have shown an inverse correlation between a diet rich in fruits, vegetables, and carotenoids and a low incidence of different types of cancer. Lycopene, the predominant carotenoid found in tomatoes, exhibits a high antioxidant capacity and has been shown to prevent cancer, as evidenced by clinical trials and studies in cell culture and animal models. In vitro studies have shown that lycopene treatment can selectively arrest cell growth and induce apoptosis in cancer cells without affecting normal cells. In vivo studies have revealed that lycopene treatment inhibits tumour growth in the liver, lung, prostate, breast, and colon. Clinical studies have shown that lycopene protects against prostate cancer. One of the main challenges in cancer prevention is the integration of new molecular findings into clinical practice. Thus, the identification of molecular biomarkers associated with lycopene levels is essential for improving our understanding of the mechanisms underlying its antineoplastic activity.

  6. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data.

    Science.gov (United States)

    Ren, Zhonglu; Wang, Wenhui; Li, Jinming

    2016-02-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristics of each subtype. Clustering analysis and discriminant analysis were utilized to discover the subtypes in two different molecular levels on 153 colon cancer samples from The Cancer Genome Atlas (TCGA) Data Portal. At gene expression level, we identified two major subtypes, ECL1 (expression cluster 1) and ECL2 (expression cluster 2) and a list of signature genes. Due to the heterogeneity of colon cancer, the subtype ECL1 can be further subdivided into three nested subclasses, and HOTAIR were found upregulated in subclass 2. At DNA methylation level, we uncovered three major subtypes, MCL1 (methylation cluster 1), MCL2 (methylation cluster 2) and MCL3 (methylation cluster 3). We found only three subtypes of CpG island methylator phenotype (CIMP) in colon cancer instead of the four subtypes in the previous reports, and we found no sufficient evidence to subdivide MCL3 into two distinct subgroups.

  7. Molecular mechanisms and theranostic potential of miRNAs in drug resistance of gastric cancer.

    Science.gov (United States)

    Yang, Wanli; Ma, Jiaojiao; Zhou, Wei; Cao, Bo; Zhou, Xin; Yang, Zhiping; Zhang, Hongwei; Zhao, Qingchuan; Fan, Daiming; Hong, Liu

    2017-11-01

    Systemic chemotherapy is a curative approach to inhibit gastric cancer cells proliferation. Despite the great progress in anti-cancer treatment achieved during the last decades, drug resistance and treatment refractoriness still extensively persists. Recently, accumulating studies have highlighted the role of miRNAs in drug resistance of gastric cancers by modulating some drug resistance-related proteins and genes expression. Pre-clinical reports indicate that miRNAs might serve as ideal biomarkers and potential targets, thus holding great promise for developing targeted therapy and personalized treatment for the patients with gastric cancer. Areas covered: This review provide a comprehensive overview of the current advances of miRNAs and molecular mechanisms underlying miRNA-mediated drug resistance in gastric cancer. We particularly focus on the potential values of drug resistance-related miRNAs as biomarkers and novel targets in gastric cancer therapy and envisage the future research developments of these miRNAs and challenges in translating the new findings into clinical applications. Expert opinion: Although the concrete mechanisms of miRNAs in drug resistance of gastric cancer have not been fully clarified, miRNA may be a promising theranostic approach. Further studies are still needed to facilitate the clinical applications of miRNAs in drug resistant gastric cancer.

  8. DETECTION OF OXIDATIVE STRESS, APOPTOSIS AND MOLECULAR LESIONS IN HUMAN OVARIAN CANCER CELLS

    Directory of Open Access Journals (Sweden)

    H. I. Falfushynska

    2016-05-01

    Full Text Available Background. Ovarian cancer has the highest mortality rate of gynaecological cancers. This is partly due to the lack of effective screening markers. Indices of oxidative stress are well-recognized prognostic criteria for tumorous transformation of tissue, but their value depends on the type of tumor and the stage of its development. Objective. The aim of this study is to clarify the relationship between antioxidant/pro-oxidant ratio and the signs of molecular lesions and apoptosis rate in blood of ovarian cancer patients and non-cancer ones. Results. The ovarian cancer group is marked by antioxidant/prooxidant balance shifting to oxidative damage in blood as the consequence of overexpression of oxyradicals (by 300%. Higher level of glutathione (by 366%, lower level of metallothioneins (by 65% as well as higher level of lipid peroxidation (by 174% and protein carbonyls (by 186% in blood of ovarian cancer patients compared to the normal ovarian group have been observed. The signs of cytotoxicity are determined in blood of ovarian cancer patients: an increased (compared to control level of DNA fragmentation (by 160%, choline esterase (up to twice, higher rate of both caspase dependent and caspase independent lysosomal mediated apoptosis. Conclusions. Cathepsin D activity both total and free, choline esterase activity, TBA-reactive substance and protein carbonyls level in blood could be used as the predictive markers of worse prognosis and the signs of human ovarian cancer.

  9. Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study.

    Science.gov (United States)

    Feng, Yuan; Zhou, Jihong; Li, Zhanhua; Jiang, Ying; Zhou, Ying

    2016-01-01

    Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines) and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5) induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID) mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.

  10. Small Molecular TRAIL Inducer ONC201 Induces Death in Lung Cancer Cells: A Preclinical Study.

    Directory of Open Access Journals (Sweden)

    Yuan Feng

    Full Text Available Tumor necrosis factor (TNF-related apoptosis-inducing ligand (TRAIL selectively targets cancer cells. The present preclinical study investigated the anti-cancer efficiency of ONC201, a first-in-class small molecule TRAIL inducer, in lung cancer cells. We showed that ONC201 was cytotoxic and anti-proliferative in both established (A549 and H460 lines and primary human lung cancer cells. It was yet non-cytotoxic to normal lung epithelial cells. Further, ONC201 induced exogenous apoptosis activation in lung cancer cells, which was evidenced by TRAIL/death receptor-5 (DR5 induction and caspase-8 activation. The caspase-8 inhibitor or TRAIL/DR5 siRNA knockdown alleviated ONC201's cytotoxicity against lung cancer cells. Molecularly, ONC201 in-activated Akt-S6K1 and Erk signalings in lung cancer cells, causing Foxo3a nuclear translocation. For the in vivo studies, intraperitoneal injection of ONC201 at well-tolerated doses significantly inhibited xenografted A549 tumor growth in severe combined immunodeficient (SCID mice. Further, ONC201 administration induced TRAIL/DR5 expression, yet inactivated Akt-S6K1 and Erk in tumor tissues. These results of the study demonstrates the potent anti-lung cancer activity by ONC201.

  11. Molecular inimitability amongst tumors: implications for precision cancer medicine in the age of personalized oncology.

    Science.gov (United States)

    Patel, Sandip P; Schwaederle, Maria; Daniels, Gregory A; Fanta, Paul T; Schwab, Richard B; Shimabukuro, Kelly A; Kesari, Santosh; Piccioni, David E; Bazhenova, Lyudmila A; Helsten, Teresa L; Lippman, Scott M; Parker, Barbara A; Kurzrock, Razelle

    2015-10-20

    Tumor sequencing has revolutionized oncology, allowing for detailed interrogation of the molecular underpinnings of cancer at an individual level. With this additional insight, it is increasingly apparent that not only do tumors vary within a sample (tumor heterogeneity), but also that each patient's individual tumor is a constellation of unique molecular aberrations that will require an equally unique personalized therapeutic regimen. We report here the results of 439 patients who underwent Clinical Laboratory Improvement Amendment (CLIA)-certified next generation sequencing (NGS) across histologies. Among these patients, 98.4% had a unique molecular profile, and aside from three primary brain tumor patients with a single genetic lesion (IDH1 R132H), no two patients within a given histology were molecularly identical. Additionally, two sets of patients had identical profiles consisting of two mutations in common and no other anomalies. However, these profiles did not segregate by histology (lung adenocarcinoma-appendiceal cancer (KRAS G12D and GNAS R201C), and lung adenocarcinoma-liposarcoma (CDK4 and MDM2 amplification pairs)). These findings suggest that most advanced tumors are molecular singletons within and between histologies, and that tumors that differ in histology may still nonetheless exhibit identical molecular portraits, albeit rarely.

  12. 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.

  13. Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling.

    Science.gov (United States)

    Karthik, Govindasamy-Muralidharan; Rantalainen, Mattias; Stålhammar, Gustav; Lövrot, John; Ullah, Ikram; Alkodsi, Amjad; Ma, Ran; Wedlund, Lena; Lindberg, Johan; Frisell, Jan; Bergh, Jonas; Hartman, Johan

    2017-11-29

    Transcriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics. In this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications. Molecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications. Our results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.

  14. Biología molecular y cáncer de tiroides Molecular biology and thyroid cancer

    Directory of Open Access Journals (Sweden)

    Juan Cassola Santana

    2010-12-01

    Full Text Available Se realiza una revisión actualizada sobre aspectos de biología molecular que servirán de base al cirujano actuante para un mejor conocimiento del cáncer tiroideo. El objetivo radica en alertar a los cirujanos sobre las nuevas evaluaciones a las que podrán someterse los tumores de la tiroides, que implicarán cambios en toda la gama de conductas actuales en estos casos. Se señalan aspectos que sin duda cambiarán los conceptos que se manejan hoy día.A updating review is carry out on the features of molecular biology as a basis for acting surgeon to a better knowledge of thyroid cancer. The objective is to alert surgeons on the new assessments for this type of cancer, implicating changes in all the range of current behaviors in these cases. The features that will change the nowadays concepts in this respect.

  15. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Human cervical cancer: therapeutic response assessment by innovative molecular strategies

    International Nuclear Information System (INIS)

    Nagarajan, Bala

    2016-01-01

    In Asia-Pacific region, the incidence of cancer of uterine cervix is high. Cancer is a multiple disease of multiple etiologies that has bearing on gene alteration that end result in abnormal cell dysfunction. We address the process interfacing infection, inflammation and oxidative damage that would lead to identify markers - to help improve patient management and bench to bedside. Radiation causes cell damage through production of reactive oxygen species. Radiation-induced DNA strand break is the primary mode of cell death. However, a secondary form of damage includes base modification or DNA adducts that are lethal on accumulation at higher levels. We analyzed polar and lipophilic adducts and found that the levels of adducts formed were independent of severity of disease status. 8 oxodG could be used as a marker to reflect patients potential to fix the lesion and response to radiation therapy. There was an increase in adduct levels in post treatment samples when compared to pre-RT, indicating radiation-induced DNA damage. Patients divided into two groups, high and low adduct formers, tend to show interindividual differences to fix the lesion that could be used to delineate radio-resistant or non-responding tumors. We have also looked at inflammatory cytokines, both by immunocytochemistry and m-RNA by RT-PCR through therapy, and generated definitive data that augur well with treatment response. The bottom line approach is prognostication and stratification. (author)

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

    Science.gov (United States)

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

    2018-01-01

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

  18. Pitfalls in lung cancer molecular pathology: how to limit them in routine practice?

    Science.gov (United States)

    Ilie, M; Hofman, P

    2012-01-01

    New treatment options in advanced non-small cell lung carcinoma (NSCLC) targeting activating epidermal growth factor receptor (EGFR) gene mutations and other genetic alterations demonstrated the clinical significance of the molecular features of specific subsets of tumors. Therefore, the development of personalized medicine has stimulated the routine integration into pathology departments of somatic mutation testing. However, clinical mutation testing must be optimized and standardized with regard to histological profile, type of samples, pre-analytical steps, methodology and result reporting. Routine molecular testing in NSCLC is currently moving beyond EGFR mutational analysis. Recent progress of targeted therapies will require molecular testing for a wide panel of mutations for a personalized molecular diagnosis. As a consequence, efficient testing of multiple molecular abnormalities is an urgent requirement in thoracic oncology. Moreover, increasingly limited tumor sample becomes a major challenge for molecular pathology. Continuous efforts should be made for safe, effective and specific molecular analyses. This must be based on close collaboration between the departments involved in the management of lung cancer. In this review we explored the practical issues and pitfalls surrounding the routine implementation of molecular testing in NSCLC in a pathology laboratory.

  19. LAMININS IN COLORECTAL CANCER: EXPRESSION, FUNCTION, PROGNOSTIC POWER AND MOLECULAR MECHANISMS

    Directory of Open Access Journals (Sweden)

    S. A. Rodin

    2017-01-01

    Full Text Available Extracellular matrix (ECM proteins are a major component of the tumor stroma. Laminins emerge as one of the main families of ECM proteins with signaling properties. Apart from the structural function, laminins and products of their degradation affect survival and differentiation of cancer cells, motility of cancer and stromal cells, angiogenesis, invasion into distant organs, and other aspects of cancer development. Here, we discus expression of laminins in colorectal cancer (CRC, studying of laminin functions in in vitro and in vivo models of CRC, and using laminins as prognostic markers of CRC. Recently, we have reported a new approach to assessing prognostic power using classifiers constructed from sets of laminin genes. The method allows for accurate prognosis of CRC and provides additional information that may suggest possible molecular mechanisms of laminin function in CRC progression.

  20. Molecular phenotyping of human ovarian cancer stem cells unravels the mechanisms for repair and chemoresistance

    DEFF Research Database (Denmark)

    Alvero, Ayesha B; Chen, Rui; Fu, Han-Hsuan

    2009-01-01

    A major burden in the treatment of ovarian cancer is the high percentage of recurrence and chemoresistance. Cancer stem cells (CSCs) provide a reservoir of cells that can self-renew, can maintain the tumor by generating differentiated cells [non-stem cells (non-CSCs)] which make up the bulk...... to form spheroids in suspension, and the ability to recapitulate in vivo the original tumor. Chemotherapy eliminates the bulk of the tumor but it leaves a core of cancer cells with high capacity for repair and renewal. The molecular properties identified in these cells may explain some of the unique...... of the tumor and may be the primary source of recurrence. We describe the characterization of human ovarian cancer stem cells (OCSCs). These cells have a distinctive genetic profile that confers them with the capacity to recapitulate the original tumor, proliferate with chemotherapy, and promote recurrence...

  1. Initiative for Molecular Profiling and Advanced Cancer Therapy and challenges in the implementation of precision medicine.

    Science.gov (United States)

    Tsimberidou, Apostolia-Maria

    In the last decade, breakthroughs in technology have improved our understanding of genomic, transcriptional, proteomic, epigenetic aberrations and immune mechanisms in carcinogenesis. Genomics and model systems have enabled the validation of novel therapeutic strategies. Based on these developments, in 2007, we initiated the IMPACT (Initiative for Molecular Profiling and Advanced Cancer Therapy) study, the first personalized medicine program for patients with advanced cancer at The University of Texas MD Anderson Cancer Center. We demonstrated that in patients referred for Phase I clinical trials, the use of tumor molecular profiling and treatment with matched targeted therapy was associated with encouraging rates of response, progression-free survival and overall survival compared to non-matched therapy. We are currently conducting IMPACT2, a randomized study evaluating molecular profiling and targeted agents in patients with metastatic cancer. Optimization of innovative biomarker-driven clinical trials that include targeted therapy and/or immunotherapeutic approaches for carefully selected patients will accelerate the development of novel drugs and the implementation of precision medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Case Study in International Cooperation: Cuba's Molecular Immunology Center and Roswell Park Cancer Institute.

    Science.gov (United States)

    Evans, Rachel; Reid, Mary; Segal, Brahm; Abrams, Scott I; Lee, Kelvin

    2018-04-01

    In 1961, the USA severed diplomatic relations with Cuba, and in 1962 an embargo was imposed on trade and financial relations with that country. It was not until five decades later that the USA and Cuba would reestablish relations. This opened the way for the New York State Trade Mission to Cuba in April 2015, during which Cuba's Molecular Immunology Center and Buffalo, New York's Roswell Park Cancer Institute signed a formal agreement that would set in motion biotechnology research collaboration to address one of the most important causes of death in both countries. Significant research from Cuba led to this groundbreaking collaboration. The purpose of this paper is to discuss the development of this cooperation, from the Molecular Immunology Center's initial investigations, through the opening of a phase I clinical trial at Roswell Park Cancer Institute with therapies developed at the Center. This cooperation was responsible for the first clinical trial for CIMAvax-EGF involving advanced-stage non-small cell lung cancer patients in the USA. A license was also approved by the US Department of the Treasury's Office of Foreign Assets Control authorizing a commercial partnership for development of biotechnology products, combining the cancer research efforts of both institutions. This unusual collaboration between Cuba and the USA-the US economic embargo and travel restrictions not withstanding-opens good prospects for expanded medical research between the two countries. While political and logistical challenges remain, the shared mission and dedication of these Cuban and US scientists points the way towards relationships that can lead to development, testing, approval and use of promising new therapies for cancer patients. KEYWORDS Biotechnology, clinical trials, cancer vaccines, cancer immunotherapy, non-small cell lung cancer, NSCLC, Cuba, USA.

  3. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

    Science.gov (United States)

    Robertson, A Gordon; Kim, Jaegil; Al-Ahmadie, Hikmat; Bellmunt, Joaquim; Guo, Guangwu; Cherniack, Andrew D; Hinoue, Toshinori; Laird, Peter W; Hoadley, Katherine A; Akbani, Rehan; Castro, Mauro A A; Gibb, Ewan A; Kanchi, Rupa S; Gordenin, Dmitry A; Shukla, Sachet A; Sanchez-Vega, Francisco; Hansel, Donna E; Czerniak, Bogdan A; Reuter, Victor E; Su, Xiaoping; de Sa Carvalho, Benilton; Chagas, Vinicius S; Mungall, Karen L; Sadeghi, Sara; Pedamallu, Chandra Sekhar; Lu, Yiling; Klimczak, Leszek J; Zhang, Jiexin; Choo, Caleb; Ojesina, Akinyemi I; Bullman, Susan; Leraas, Kristen M; Lichtenberg, Tara M; Wu, Catherine J; Schultz, Nicholaus; Getz, Gad; Meyerson, Matthew; Mills, Gordon B; McConkey, David J; Weinstein, John N; Kwiatkowski, David J; Lerner, Seth P

    2017-10-19

    We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology. Clustering by mRNA, long non-coding RNA (lncRNA), and miRNA expression converged to identify subsets with differential epithelial-mesenchymal transition status, carcinoma in situ scores, histologic features, and survival. Our analyses identified 5 expression subtypes that may stratify response to different treatments. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Molecular imaging in the management of cervical cancer

    Directory of Open Access Journals (Sweden)

    Chyong-Huey Lai

    2012-08-01

    Full Text Available Positron emission tomography (PET, magnetic resonance imaging (MRI, and integrated 18-fluorodeoxyglucose (18F-FDG PET/computed tomography are valuable techniques for assessing prognosis, treatment response after the completion of concurrent chemoradiation, suspicious or documented recurrence, unexplained post therapy elevations in tumor markers, and the response to salvage treatment when managing cervical cancer. However, PET plays a limited role in the primary staging of MRI-defined node-negative patients. Currently, 18F-FDG is still the only tracer approved for routine use, but several novel targeting PET compounds, high-Tesla MRI machines, diffusion-weighted imaging without contrast, and dynamic nuclear polarized-enhanced 13C-MR spectroscopic imaging may hold promising applications.

  5. Transcription-Based Molecular Imaging and Gene Therapy for Castration-resistant and Metastatic Prostate Cancer in Translational Models

    OpenAIRE

    Jiang, Ziyue

    2013-01-01

    The advanced stage of prostate cancer is the second leading cause of cancer-related death for American men. Novel, effective treatment options and more cancer-specific diagnostic tools are urgently needed to facilitate patient management. Here, we explored the construction and application of an array of gene-based molecular imaging and therapeutic vectors in a variety of clinically relevant settings. These vectors exploit prostate cancer-specific promoters to control the transcription of imag...

  6. Oligometastatic prostate cancer: shaping the definition with molecular imaging and an improved understanding of tumor biology.

    Science.gov (United States)

    Joice, Gregory A; Rowe, Steven P; Pienta, Kenneth J; Gorin, Michael A

    2017-11-01

    The aim of this review is to discuss how novel imaging modalities and molecular markers are shaping the definition of oligometastatic prostate cancer. To effectively classify a patient as having oligometastatic prostate cancer, diagnostic tests must be sensitive enough to detect subtle sites of metastatic disease. Conventional imaging modalities can readily detect widespread polymetastatic disease but do not have the sensitivity necessary to reliably classify patients as oligometastatic. Molecular imaging using both metabolic- and molecularly-targeted radiotracers has demonstrated great promise in aiding in our ability to define the oligometastatic state. Perhaps the most promising data to date have been generated with radiotracers targeting prostate-specific membrane antigen. In addition, early studies are beginning to define biologic markers in the oligometastatic state that may be indicative of disease with minimal metastatic potential. Recent developments in molecular imaging have allowed for improved detection of metastatic prostate cancer allowing for more accurate staging of patients with oligometastatic disease. Future development of biologic markers may assist in defining the oligometastatic state and determining prognosis.

  7. MgH Rydberg series: Transition energies from electron propagator theory and oscillator strengths from the molecular quantum defect orbital method

    Science.gov (United States)

    Corzo, H. H.; Velasco, A. M.; Lavín, C.; Ortiz, J. V.

    2018-02-01

    Vertical excitation energies belonging to several Rydberg series of MgH have been inferred from 3+ electron-propagator calculations of the electron affinities of MgH+ and are in close agreement with experiment. Many electronically excited states with n > 3 are reported for the first time and new insight is given on the assignment of several Rydberg series. Valence and Rydberg excited states of MgH are distinguished respectively by high and low pole strengths corresponding to Dyson orbitals of electron attachment to the cation. By applying the Molecular Quantum Defect Orbital method, oscillator strengths for electronic transitions involving Rydberg states also have been determined.

  8. Molecular image in biomedical research. Molecular imaging unit of the National Cancer Research Center

    International Nuclear Information System (INIS)

    Perez Bruzon, J.; Mulero Anhiorte, F.

    2010-01-01

    This article has two basic objectives. firstly, it will review briefly the most important imaging techniques used in biomedical research indicting the most significant aspects related to their application in the preclinical stage. Secondly, it will present a practical application of these techniques in a pure biomedical research centre (not associated to a clinical facility). Practical aspects such as organisation, equipment, work norms, shielding of the Spanish National Cancer Research Centre (CNIO) Imaging Unit will be shown. This is a pioneering facility in the application of these techniques in research centres without any dependence or any direct relationship with other hospital Nuclear Medicine services. (Author) 7 refs.

  9. A network-based biomarker approach for molecular investigation and diagnosis of lung cancer

    Directory of Open Access Journals (Sweden)

    Chen Bor-Sen

    2011-01-01

    Full Text Available Abstract Background Lung cancer is the leading cause of cancer deaths worldwide. Many studies have investigated the carcinogenic process and identified the biomarkers for signature classification. However, based on the research dedicated to this field, there is no highly sensitive network-based method for carcinogenesis characterization and diagnosis from the systems perspective. Methods In this study, a systems biology approach integrating microarray gene expression profiles and protein-protein interaction information was proposed to develop a network-based biomarker for molecular investigation into the network mechanism of lung carcinogenesis and diagnosis of lung cancer. The network-based biomarker consists of two protein association networks constructed for cancer samples and non-cancer samples. Results Based on the network-based biomarker, a total of 40 significant proteins in lung carcinogenesis were identified with carcinogenesis relevance values (CRVs. In addition, the network-based biomarker, acting as the screening test, proved to be effective in diagnosing smokers with signs of lung cancer. Conclusions A network-based biomarker using constructed protein association networks is a useful tool to highlight the pathways and mechanisms of the lung carcinogenic process and, more importantly, provides potential therapeutic targets to combat cancer.

  10. Molecular Characterization and Clinical Relevance of Metabolic Expression Subtypes in Human Cancers

    Directory of Open Access Journals (Sweden)

    Xinxin Peng

    2018-04-01

    Full Text Available Summary: Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes—modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility. : Peng et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to characterize tumor subtypes based on the expression of seven metabolic pathways. They find metabolic expression subtypes are associated with patient survivals and suggest the therapeutic and predictive relevance of subtype-related master regulators. Keywords: The Cancer Genome Atlas, tumor subtypes, prognostic markers, somatic drivers, master regulator, therapeutic targets, drug sensitivity, carbohydrate metabolism

  11. Molecular characterization of the stomach microbiota in patients with gastric cancer and controls

    Energy Technology Data Exchange (ETDEWEB)

    Dicksved, J.; Lindberg, M.; Rosenquist, M.; Enroth, H.; Jansson, J.K.; Engstrand, L.

    2009-01-15

    Persistent infection of the gastric mucosa by Helicobacter pylori, can initiate an inflammatory cascade that progresses into atrophic gastritis, a condition associated with reduced capacity for secretion of gastric acid and an increased risk in developing gastric cancer. The role of H. pylori as an initiator of inflammation is evident but the mechanism for development into gastric cancer has not yet been proven. A reduced capacity for gastric acid secretion allows survival and proliferation of other microbes that normally are killed by the acidic environment. It has been postulated that some of these species may be involved in the development of gastric cancer, however their identities are poorly defined. In this study, the gastric microbiota from ten patients with gastric cancer was characterized and compared with five dyspeptic controls using the molecular profiling approach, terminal-restriction fragment length polymorphism (T-RFLP), in combination with 16S rRNA gene cloning and sequencing. T-RFLP analysis revealed a complex bacterial community in the cancer patients that was not significantly different from the controls. Sequencing of 140 clones revealed 102 phylotypes, with representatives from five bacterial phyla (Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria). The data revealed a relatively low abundance of H. pylori and showed that the gastric cancer microbiota was instead dominated by different species of the genera Streptococcus, Lactobacillus, Veillonella and Prevotella. The respective role of these species in development of gastric cancer remains to be determined.

  12. Molecular epigenetics in the management of ovarian cancer: Are we investigating a rational clinical promise?

    Directory of Open Access Journals (Sweden)

    Ha eNguyen

    2014-04-01

    Full Text Available Epigenetics is essentially a phenotypical change in gene expression without any alteration of the DNA sequence; the emergence of epigenetics in cancer research and mainstream oncology is fueling new hope. However, it is not yet known whether this knowledge will translate to improved clinical management of ovarian cancer. In this malignancy, women are still undergoing chemotherapy similar to what was approved in 1978, which to this day represents one of the biggest breakthroughs for treating ovarian cancer. While liquid tumors are benefitting from epigenetically-related therapies, solid tumors like ovarian cancer are not (yet?. Herein we will review the science of molecular epigenetics, especially DNA methylation, histone modifications and microRNA, but also include transcription factors since they, too, are important in ovarian cancer. Preclinical and clinical research on the role of epigenetic modifications is summarized as well. Sadly, ovarian cancer remains an idiopathic disease, for the most part, and there are many areas of patient management which could benefit from improved technology. This review will also highlight the evidence suggesting that epigenetics may have preclinical utility in pharmacology and clinical applications for prognosis and diagnosis. Lastly, drugs currently in clinical trials (i.e. histone deacetylase inhibitors are discussed along with the promise for epigenetics in the exploitation of chemoresistance. Whether epigenetics will ultimately be the answer to better management in ovarian cancer is currently unknown; what we have now is hope.

  13. Right Versus Left Colon Cancer Biology: Integrating the Consensus Molecular Subtypes.

    Science.gov (United States)

    Lee, Michael S; Menter, David G; Kopetz, Scott

    2017-03-01

    Although clinical management of colon cancer generally has not accounted for the primary tumor site, left-sided and right-sided colon cancers harbor different clinical and biologic characteristics. Right-sided colon cancers are more likely to have genome-wide hypermethylation via the CpG island methylator phenotype (CIMP), hypermutated state via microsatellite instability, and BRAF mutation. There are also differential exposures to potential carcinogenic toxins and microbiota in the right and left colon. Gene expression analyses further shed light on distinct biologic subtypes of colorectal cancers (CRCs), with 4 consensus molecular subtypes (CMSs) identified. Importantly, these subtypes are differentially distributed between right- and left-sided CRCs, with greater proportions of the "microsatellite unstable/immune" CMS1 and the "metabolic" CMS3 subtypes found in right-sided colon cancers. This review summarizes important biologic distinctions between right- and left-sided CRCs that likely impact prognosis and may predict for differential responses to biologic therapy. Given the inferior prognosis of stage III-IV right-sided CRCs and emerging data suggesting that anti-epidermal growth factor receptor antibody therapy is associated with worse survival in right-sided stage IV CRCs compared with left-sided cancers, these biologic differences between right- and left-sided CRCs provide critical context and may provide opportunities to personalize therapy. Copyright © 2017 by the National Comprehensive Cancer Network.

  14. Morphologic and molecular study of lung cancers associated with idiopathic pulmonary fibrosis and other pulmonary fibroses.

    Science.gov (United States)

    Guyard, Alice; Danel, Claire; Théou-Anton, Nathalie; Debray, Marie-Pierre; Gibault, Laure; Mordant, Pierre; Castier, Yves; Crestani, Bruno; Zalcman, Gérard; Blons, Hélène; Cazes, Aurélie

    2017-06-15

    Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges. Their incidence may increase with new more efficient lung fibrosis treatments. Our aim was to describe a cohort of lung cancers associated with idiopathic pulmonary fibrosis (IPF) and other lung fibrotic disorders (non-IPF), and to characterize their molecular alterations using immunohistochemistry and next-generation sequencing (NGS). Thirty-one cancer samples were collected from 2001 to 2016 in two French reference centers for pulmonary fibrosis - 18 for IPF group and 13 for non-IPF group. NGS was performed using an ampliseq panel to analyze hotspots and targeted regions in 22 cancer-associated genes. ALK, ROS1 and PD-L1 expressions were assessed by immunohistochemistry. Squamous cell carcinoma was the most frequent histologic subtype in the IPF group (44%), adenocarcinoma was the most frequent subtype in the non-IPF group (62%). Forty-one mutations in 13 genes and one EGFR amplification were identified in 25 samples. Two samples had no mutation in the selected panel. Mutations were identified in TP53 (n = 20), MET (n = 4), BRAF (n = 3), FGFR3, PIK3CA, PTEN, STK11 (n = 2), SMAD4, CTNNB1, DDR2, ERBB4, FBXW7 and KRAS (n = 1) genes. No ALK and ROS1 expressions were identified. PD-L1 was expressed in 10 cases (62%) with only one (6%) case >50%. This extensive characterization of lung fibrosis-associated cancers evidenced molecular alterations which could represent either potential therapeutic targets either clues to the pathophysiology of these particular tumors. These findings support the relevance of large molecular characterization of every lung fibrosis-associated cancer.

  15. Prediction consistency and clinical presentations of breast cancer molecular subtypes for Han Chinese population

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    Huang Chi-Cheng

    2012-09-01

    Full Text Available Abstract Background Breast cancer is a heterogeneous disease in terms of transcriptional aberrations; moreover, microarray gene expression profiles had defined 5 molecular subtypes based on certain intrinsic genes. This study aimed to evaluate the prediction consistency of breast cancer molecular subtypes from 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 as well as clinical presentations of each molecualr subtype in Han Chinese population. Methods In all, 169 breast cancer samples (44 from Taiwan and 125 from China of Han Chinese population were gathered, and the gene expression features corresponding to 3 distinct intrinsic gene sets (Sørlie 500, Hu 306 and PAM50 were retrieved for molecular subtype prediction. Results For Sørlie 500 and Hu 306 intrinsic gene set, mean-centring of genes and distance-weighted discrimination (DWD remarkably reduced the number of unclassified cases. Regarding pairwise agreement, the highest predictive consistency was found between Hu 306 and PAM50. In all, 150 and 126 samples were assigned into identical subtypes by both Hu 306 and PAM50 genes, under mean-centring and DWD. Luminal B tended to show a higher nuclear grade and have more HER2 over-expression status than luminal A did. No basal-like breast tumours were ER positive, and most HER2-enriched breast tumours showed HER2 over-expression, whereas, only two-thirds of ER negativity/HER2 over-expression tumros were predicted as HER2-enriched molecular subtype. For 44 Taiwanese breast cancers with survival data, a better prognosis of luminal A than luminal B subtype in ER-postive breast cancers and a better prognosis of basal-like than HER2-enriched subtype in ER-negative breast cancers was observed. Conclusions We suggest that the intrinsic signature Hu 306 or PAM50 be used for breast cancers in the Han Chinese population during molecular subtyping. For the prognostic value and decision making based on intrinsic subtypes, further prospective

  16. Breast Cancer Patients Have Greatly Benefited from the Progress in Molecular Oncology.

    Directory of Open Access Journals (Sweden)

    Bernd L Groner

    2016-09-01

    Full Text Available Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public money, it is perfectly legitimate to ask if these large expenses are worth it. In this brief commentary, we recapitulate some of the breakthroughs that mark the history of breast cancer research over the past decades and emphasize the resulting benefits for afflicted women. In 1971, only 40% of women diagnosed with breast cancer would live another 10 years. Today, nearly 80% of women reach that significant milestone in most developed countries. This dramatic change has afforded breast cancer patients many productive years and a better quality of life. Progress resulted largely from advances in the understanding of the molecular details of the disease and their translation into innovative, rationally designed therapies. These developments are founded on the revolution in molecular and cellular biology, an entirely new array of methods and technologies, the enthusiasm, optimism, and diligence of scientists and clinicians, and the considerable funding efforts from public and private sources. We were lucky to be able to spend our productive years in a period of scientific upheaval in which methods and concepts were revolutionized and that allowed us to contribute, within the global scientific community, to the progress in basic science and clinical practice.

  17. Breast Cancer Patients Have Greatly Benefited from the Progress in Molecular Oncology.

    Science.gov (United States)

    Groner, Bernd L; Hynes, Nancy E

    2016-09-01

    Cancer research has become a global enterprise, and the number of researchers, as well as the cost for their activities, has skyrocketed. The budget for the National Cancer Institute of the United States National Institutes of Health alone was US$5.2 billion in 2015. Since most of the research is funded by public money, it is perfectly legitimate to ask if these large expenses are worth it. In this brief commentary, we recapitulate some of the breakthroughs that mark the history of breast cancer research over the past decades and emphasize the resulting benefits for afflicted women. In 1971, only 40% of women diagnosed with breast cancer would live another 10 years. Today, nearly 80% of women reach that significant milestone in most developed countries. This dramatic change has afforded breast cancer patients many productive years and a better quality of life. Progress resulted largely from advances in the understanding of the molecular details of the disease and their translation into innovative, rationally designed therapies. These developments are founded on the revolution in molecular and cellular biology, an entirely new array of methods and technologies, the enthusiasm, optimism, and diligence of scientists and clinicians, and the considerable funding efforts from public and private sources. We were lucky to be able to spend our productive years in a period of scientific upheaval in which methods and concepts were revolutionized and that allowed us to contribute, within the global scientific community, to the progress in basic science and clinical practice.

  18. Molecular characteristics of endometrial cancer coexisting with peritoneal malignant mesothelioma in Li-Fraumeni-like syndrome.

    Science.gov (United States)

    Chao, Angel; Lai, Chyong-Huey; Lee, Yun-Shien; Ueng, Shir-Hwa; Lin, Chiao-Yun; Wang, Tzu-Hao

    2015-01-15

    Endometrial cancer that occurs concurrently with peritoneal malignant mesothelioma (PMM) is difficult to diagnose preoperatively. A postmenopausal woman had endometrial cancer extending to the cervix, vagina and pelvic lymph nodes, and PMM in bilateral ovaries, cul-de-sac, and multiple peritoneal sites. Adjuvant therapies included chemotherapy and radiotherapy. Targeted, massively parallel DNA sequencing and molecular inversion probe microarray analysis revealed a germline TP53 mutation compatible with Li-Fraumeni-like syndrome, somatic mutations of PIK3CA in the endometrial cancer, and a somatic mutation of GNA11 and JAK3 in the PMM. Large-scale genomic amplifications and some deletions were found in the endometrial cancer. The patient has been stable for 24 months after therapy. One of her four children was also found to carry the germline TP53 mutation. Molecular characterization of the coexistent tumors not only helps us make the definite diagnosis, but also provides information to select targeted therapies if needed in the future. Identification of germline TP53 mutation further urged us to monitor future development of malignancies in this patient and encourage cancer screening in her family.

  19. Molecular Determinants of Colon Cancer Susceptibility in the East and West.

    Science.gov (United States)

    Abdel-Rahman, W M; Faris, M E; Peltomaki, P

    2017-01-01

    The currently available knowledge of factors that dictate the development and progression as well as the clinical outcome of colorectal cancers (CRC) is mainly derived from Western countries. Considerable number of publications document different incidence rates and contrasting clinical features of CRC in various groups such as the differences between urban vs. rural areas, young vs. old age and the East vs. the West. In particular, Egyptian CRC is a surprisingly young age disease with higher proportion of poorly differentiated and advanced stage cancers as compared to the Western counterparts. Less number of publications addressed the molecular genetics and epigenetic basis of these differences. The available data on CRC and other cancers support a substantial role of several environmental risk factors which impinge on the epigenome and alter the overall cellular and tissue homeostasis. Thus, environmental factors could play a role in predisposition to CRC in general as well as in shaping distinct disease phenotypes in different settings. On the other hand, the environment offers a wide range of preventive modalities including a selection of dietary chemopreventive agents which could play a significant role in fighting cancer at early stages. We here compare the clinical and molecular characteristics of Eastern and Western CRC based on the latest literature. The genetic, epigenetic and environmental etiologies for the observed differences are discussed. Finally, prospects for cancer prevention in light of the increased etiologic understanding are outlined. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Challenges and future direction of molecular research in air pollution-related lung cancers.

    Science.gov (United States)

    Shahadin, Maizatul Syafinaz; Ab Mutalib, Nurul Syakima; Latif, Mohd Talib; Greene, Catherine M; Hassan, Tidi

    2018-04-01

    Hazardous air pollutants or chemical release into the environment by a variety of natural and/or anthropogenic activities may give adverse effects to human health. Air pollutants such as sulphur dioxide (SO2), nitrogen oxides (NOx), carbon monoxide (CO), heavy metals and particulate matter (PM) affect number of different human organs, especially the respiratory system. The International Agency for Research on Cancer (IARC) reported that ambient air pollution is a cause of lung cancer. Recently, the agency has classified outdoor air pollution as well as PM air pollution as Group 1 carcinogens. In addition, several epidemiological studies have shown a positive association between air pollutants to lung cancer risks and mortality. However, there are only a few studies examining the molecular effects of air pollution exposure specifically in lung cancer due to multiple challenges to mimic air pollution exposure in basic experimentation. Another major issue is the lack of adequate adjustments for exposure misclassification as air pollution may differ temporo-spatially and socioeconomically. Thus, the purpose of this paper is to review the current molecular understanding of air pollution-related lung cancer and potential future direction in this challenging yet important research field. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

    Science.gov (United States)

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

    Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

  2. 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.

  3. Molecular imaging of hypoxia in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Yip, Connie; Blower, Philip J.; Goh, Vicky; Landau, David B.; Cook, Gary J.R.

    2015-01-01

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  4. Molecular imaging of hypoxia in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yip, Connie [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); National Cancer Centre, Department of Radiation Oncology, Singapore (Singapore); St Thomas' Hospital, Imaging 2, London (United Kingdom); Blower, Philip J. [King' s College London, St Thomas' Hospital, Department of Imaging Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Goh, Vicky [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Landau, David B. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Clinical Oncology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Cook, Gary J.R. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Clinical PET Imaging Centre, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2015-05-01

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  5. Molecular profiling of synchronous and metachronous cancers of the pancreas reveal molecular mimicry between samples from the same patient.

    Science.gov (United States)

    Talbott, Vanessa A; Yeo, Charles J; Brody, Jonathan R; Witkiewicz, Agnieszka K

    2012-07-01

    Pancreatic ductal adenocarcinoma (PDA) is rarely a survivable disease. In rare cases, separate synchronous tumors are discovered at the time of resection, while in others, patients present with a metachronous cancer after prior surgical resection. Studying molecular markers of synchronous and metachronous lesions may aid to clarify the biology of this often deadly disease. Two patients presented with synchronous tumors (each one with a tumor in the pancreatic head/neck and the other in the tail, designated patients A and B). An additional patient (patient C) underwent an R0 resection for PDA of the head and recurred 1.5 y later with PDA in the tail. Genomic DNA was laser capture microdissected (LCM) from the tumor and molecular analysis was performed. K-ras status and loss of heterozygosity (LOH) were determined from multiple specimens for each case. All samples from each patient harbored identical K-ras mutations. In patient A, the tumor at the head of the pancreas had more clonal genetic instability as reflected by LOH analysis over multiple LCM samples. Patient B had more genetic instability in the tail lesion compared with the neck. Patient C had virtually the identical molecular profile in both tumors, supporting the notion that both tumors were related. We conclude that the synchronous and metachronous tumors likely are initiated from identical precursor lesions and/or events (i.e., K-ras mutations). Future studies will need to investigate if these tumors will respond similarly to adjuvant therapies targeted against the clonal molecular events in the tumor. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Mechanism-based classification and physical therapy management of persons with cancer pain: A prospective case series

    Directory of Open Access Journals (Sweden)

    Senthil P Kumar

    2013-01-01

    Full Text Available Context: Mechanism-based classification (MBC was established with current evidence and physical therapy (PT management methods for both cancer and for noncancer pain. Aims: This study aims to describe the efficacy of MBC-based PT in persons with primary complaints of cancer pain. Settings and Design: A prospective case series of patients who attended the physiotherapy department of a multispecialty university-affiliated teaching hospital. Material and Methods: A total of 24 adults (18 female, 6 male aged 47.5 ± 10.6 years, with primary diagnosis of heterogeneous group of cancer, chief complaints of chronic disabling pain were included in the study on their consent for participation The patients were evaluated and classified on the basis of five predominant mechanisms for pain. Physical therapy interventions were recommended based on mechanisms identified and home program was prescribed with a patient log to ensure compliance. Treatments were given in five consecutive weekly sessions for five weeks each of 30 min duration. Statistical Analysis Used: Pre-post comparisons for pain severity (PS and pain interference (PI subscales of Brief pain inventory-Cancer pain (BPI-CP and, European organization for research and treatment in cancer-quality of life questionnaire (EORTC-QLQ-C30 were done using Wilcoxon signed-rank test at 95% confidence interval using SPSS for Windows version 16.0 (SPSS Inc, Chicago, IL. Results: There were statistically significant ( P < 0.05 reduction in pain severity, pain interference and total BPI-CP scores, and the EORTC-QLQ-C30. Conclusion: MBC-PT was effective for improving BPI-CP and EORTC-QLQ-C30 scores in people with cancer pain.

  7. Thyroid cancer post radioactive iodine treatment for hyperthyroidism - case series and review of the literature.

    Science.gov (United States)

    Al Eyadeh, Abdallah A; Al-Sarihin, Khaldon; Etewi, Suzan; Al-Omari, Ahmed; Al-Asa'd, Rania Atallah; Haddad, Fares Halim

    2017-01-01

    To assess the rate of thyroid cancer and mortality rate in a cohort of patients who received RAI¹³¹ treatment for hyperthyroidism and to report the index cases' characteristics and management MATERIAL AND METHODS: A cohort of 264 patients who received RAI¹³¹ treatment for different causes of thyrotoxicosis were followed up over a period of 18 years (1996-2014) by physical exam, radiological evaluation and serial thyroid function tests. During the follow up period, three cases of thyroid cancer were identified. The prevalence of thyroid cancer was 1.136% of cases who received RAI¹³¹. The relative risk was 378.79 (95% CI: 76.8 effect relationship between RAI and thyroid cancer could be established, these cases highlights the importance of life-long surveillance of patients who receive RAI¹³¹.

  8. Molecular Pathways: Fumarate Hydratase-Deficient Kidney Cancer: Targeting the Warburg Effect in Cancer

    Science.gov (United States)

    Linehan, W. Marston; Rouault, Tracey A.

    2015-01-01

    Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a hereditary cancer syndrome in which affected individuals are at risk for development of cutaneous and uterine leiomyomas and an aggressive form of type II papillary kidney cancer. HLRCC is characterized by germline mutation of the tricarboxylic acid cycle (TCA) enzyme, fumarate hydratase (FH). FH-deficient kidney cancer is characterized by impaired oxidative phosphorylation and a metabolic shift to aerobic glycolysis, a form of metabolic reprogramming referred to as the Warburg effect. Increased glycolysis generates ATP needed for increased cell proliferation. In FH-deficient kidney cancer levels of AMPK, a cellular energy sensor, are decreased; resulting in diminished p53 levels, decreased expression of the iron importer, DMT1, leading to low cellular iron levels, and to enhanced fatty acid synthesis by diminishing phosphorylation of acetyl CoA carboxylase, a rate limiting step for fatty acid synthesis. Increased fumarate and decreased iron levels in FH-deficient kidney cancer cells inactivate prolyl hydroxylases, leading to stabilization of HIF1α, and increased expression of genes such as vascular endothelial growth factor (VEGF) and GLUT1 to provide fuel needed for rapid growth demands. Several therapeutic approaches for targeting the metabolic basis of FH-deficient kidney cancer are under development or are being evaluated in clinical trials, including the use of agents such as metformin, which would reverse the inactivation of AMPK, approaches to inhibit glucose transport, LDH-A, the anti-oxidant response pathway, the heme oxygenase pathway and approaches to target the tumor vasculature and glucose transport with agents such as bevacizumab and erlotinib. These same types of metabolic shifts, to aerobic glycolysis with decreased oxidative phosphorylation, have been found in a wide variety of other cancer types. Targeting the metabolic basis of a rare cancer such as fumarate hydratase

  9. Clinical librarian support for rapid review of clinical utility of cancer molecular biomarkers.

    Science.gov (United States)

    Geng, Yimin; Fowler, Clara S; Fulton, Stephanie

    2015-01-01

    The clinical librarian used a restricted literature searching and quality-filtering approach to provide relevant clinical evidence for the use of cancer molecular biomarkers by institutional policy makers and clinicians in the rapid review process. The librarian-provided evidence was compared with the cited references in the institutional molecular biomarker algorithm. The overall incorporation rate of the librarian-provided references into the algorithm was above 80%. This study suggests the usefulness of clinical librarian expertise for clinical practice. The searching and filtering methods for high-level evidence can be adopted by information professionals who are involved in the rapid literature review.

  10. Isoforms of thyroxine-binding globulin as a model for molecular epidemiology of human cancer risk

    International Nuclear Information System (INIS)

    Golovaty, A.S.; Lapko, A.G.

    2000-01-01

    The novel field of molecular epidemiology of human cancer risk has added a new branch to classical epidemiology by providing a direct link between human cancer and carcinogen exposure. It was estimated that about 80% of cancers are due to environmental factors. The blood proteins are almost certainly targets for modification in human cancer, and their identification and characterization will be of primary importance in the development of the new and rapidly evolving field of molecular epidemiology. Among blood proteins that are altered in human cancer, TBG occupies a special place because the level of human blood TBG is the most sensitive to intensification of biosynthesis and proliferation processes in organisms in different types of cancer. The increase of TBG concentration in cancer can be result from both activation of TBG biosynthesis in liver or altering of post translation glycosylation that prolongs protein survival time. The molecular basis for the change in the properties of TBG in cancer is unknown. These distinctive changes could have important consequences for the function of TBG in cancer and may help to develop more precise markers for monitoring pathological progression in this disease. Considerable variability and subtlety can occur in the carbohydrate composition and structure of serum glycoproteins in disease. This can be either as a major change, such as an increase in the number of oligosaccharide branches at a particular glycosylation site or as a minor change such as the addition of an extra fucose or sialic acid residue. Increased fucosylation has also been reported for transferrin and alpha-fetoprotein in liver cancer; thyroglobulin in thyroid cancer, IgG in myeloma, haptoglobin in ovarian cancer. The last own studies have shown that in clinically healthy teenagers born in Khojniki (137 Cs 185-555 kBq/m), we have found an unusual thyroid profile exhibiting increased levels of total triiodothyronine (T3), total thyroxine (T4), and thyroxine

  11. Molecular-targeted nanotherapies in cancer: enabling treatment specificity.

    Science.gov (United States)

    Blanco, Elvin; Hsiao, Angela; Ruiz-Esparza, Guillermo U; Landry, Matthew G; Meric-Bernstam, Funda; Ferrari, Mauro

    2011-12-01

    Chemotherapy represents a mainstay and powerful adjuvant therapy in the treatment of cancer. The field has evolved from drugs possessing all-encompassing cell-killing effects to those with highly targeted, specific mechanisms of action; a direct byproduct of enhanced understanding of tumorigenic processes. However, advances regarding development of agents that target key molecules and dysregulated pathways have had only modest impacts on patient survival. Several biological barriers preclude adequate delivery of drugs to tumors, and remain a formidable challenge to overcome in chemotherapy. Currently, the field of nanomedicine is enabling the delivery of chemotherapeutics, including repositioned drugs and siRNAs, by giving rise to carriers that provide for protection from degradation, prolonged circulation times, and increased tumor accumulation, all the while resulting in reduced patient morbidity. This review aims to highlight several innovative, nanoparticle-based platforms with the potential of providing clinical translation of several novel chemotherapeutic agents. We will also summarize work regarding the development of a multistage drug delivery strategy, a robust carrier platform designed to overcome several biological barriers while en route to tumors. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  12. A QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP AND MOLECULAR DOCKING STUDY ON A SERIES OF PYRIMIDINES ACTING AS ANTI-HEPATITIS C VIRUS AGENTS

    Directory of Open Access Journals (Sweden)

    Sakshi Gupta

    2013-12-01

    Full Text Available A QSAR and molecular modeling study was performed on a series of pyrimidines acting as hepatitis C virus inhibitors. In this case, anti-HCV potency of the compounds was found to be significantly correlated with the hydrophobic property of the molecule, Kier’s first-order valence molecular connectivity index for a particular substituent, total structure connectivity index of the molecule, and an indicator parameter used for the presence of benzothiazole ring. The validity of the correlation was judged by leave-one-out jackknife procedure and predicting the activity of some test compounds. Using the correlation obtained, some new compounds of high potency have been predicted in the series. A docking study using Molegro Virtual Docker was performed on these predicted compounds to decipher their interactions with the receptor. It was observed that all the predicted compounds had better interaction energy and docking score than the ligand complexed with the protein.

  13. Ovarian cancer at young age: the contribution of mismatch-repair defects in a population-based series of epithelial ovarian

    DEFF Research Database (Denmark)

    Domanska, K; Malander, S; Måsbäck, A

    2007-01-01

    age is a hallmark of heredity, and ovarian cancers associated with HNPCC have been demonstrated to develop at a particularly early age. We used the Swedish Cancer Registry to identify a population-based series of 98 invasive epithelial ovarian cancers that developed before 40 years. Mucinous......At least one of ten patients with ovarian cancer is estimated to develop their tumor because of heredity with the breast and ovarian cancer syndrome due to mutations in the BRCA1 and BRCA2 genes and hereditary nonpolyposis colorectal cancer (HNPCC) being the major genetic causes. Cancer at young...... and endometrioid cancers were overrepresented and were diagnosed in 27% and 16% of the tumors, respectively. Immunostaining using antibodies against MLH1, PMS2, MSH2, and MSH6 was used to assess the mismatch-repair status and revealed loss of expression of MLH1/PMS2 in two cases, loss of MSH2/MSH6 in one case...

  14. Current evidence for universal molecular testing for colorectal cancer patients

    Directory of Open Access Journals (Sweden)

    Fábio Guilherme Campos

    2017-07-01

    Full Text Available Background: Risk assessment for Lynch Syndrome may be a complex and challenging task. Demonstration of germline mutations has the benefits of confirming Lynch Syndrome diagnosis and may also provide screening and surgical orientation for affected members and relief for non-affected relatives. Objective: The present paper aimed to critically review the criteria to diagnose Lynch Syndrome, focusing the attention on the new perspective of adopting universal screening for patients diagnosed with colorectal cancer. Methods: We performed a literature review about the rationale and preliminary results of universal testing for Lynch Syndrome. Results: The use of selective eligibility criteria to determine who should undergo Lynch Syndrome testing may fail in a substantial proportion of cases. Moreover, universal strategy is feasible, cost-effective and more sensitive than previous methods. However, there still exist problems regarding clinical practice implementation and compliance either by medical doctors and patients. Conclusions: Standard guidelines for colorectal cancer screening are not ideal to provide early detection of Lynch Syndrome patients. And although universal screening has been associated with an increased identification of Lynch Syndrome patients, a successful implementation of this approach is still limited by the lack of clinical expertise among physicians, and also requires standardization of the existing protocols for routine genetic screening. Resumo: Introdução: A avaliação de risco para síndrome de Lynch (SL pode ser tarefa complexa e desafiadora. A demonstração de mutações na linha germinal resulta em benefícios, como a confirmação do diagnóstico de SL e também pode proporcionar orientações para a triagem e procedimentos cirúrgicos para os membros afetados, além de trazer alívio para os parentes não afetados. Objetivo: Este artigo teve por objetivo oferecer uma revisão crítica dos critérios para o diagn

  15. Successful Treatment of Advanced Metastatic Prostate Cancer following Chemotherapy Based on Molecular Profiling

    Directory of Open Access Journals (Sweden)

    Charles E. Myers

    2012-03-01

    Full Text Available After Taxotere fails, treatment options for metastatic prostate cancer are limited. The three drugs with FDA approval in this setting, Jevtana, Provenge and Zytiga, are associated with median survivals of less than 2 years. In part, the impact on survival is the result of low response rates, indicating a significant proportion of patients exhibiting de novo resistance to these agents. An alternate approach is to let treatment selection be governed by gene expression profiling so that the treatment is tailored to the specific patient. Here, we report a case of metastatic prostate cancer with a dramatic response to treatment selected based on molecular profiling. This patient had failed LHRH agonist, bicalutamide, Taxotere, and doxorubicin. Molecular profiling showed overexpression of the androgen receptor and he had a dramatic response of measurable disease to second-line hormonal therapy with ketoconazole, estrogen and Leukine.

  16. Racial Variations in Prostate Cancer Molecular Subtypes and Androgen Receptor Signaling Reflect Anatomic Tumor Location.

    Science.gov (United States)

    Faisal, Farzana A; Sundi, Debasish; Tosoian, Jeffrey J; Choeurng, Voleak; Alshalalfa, Mohammed; Ross, Ashley E; Klein, Eric; Den, Robert; Dicker, Adam; Erho, Nicholas; Davicioni, Elai; Lotan, Tamara L; Schaeffer, Edward M

    2016-07-01

    Prostate cancer (PCa) subtypes based on ETS gene expression have been described. Recent studies suggest there are racial differences in tumor location, with PCa located anteriorly more often among African-American (AA) compared to Caucasian-American (CA) men. In this retrospective analysis of a multi-institutional cohort treated by radical prostatectomy (179 CA, 121 AA), we evaluated associations among molecular subtype, race, anatomic tumor location, and androgen receptor (AR) signaling. Subtype (m-ERG(+), m-ETS(+), m-SPINK1(+), or triple-negative) was determined using distribution-based outlier analysis. AR signaling was investigated using gene expression profiling of canonical AR targets. m-ERG(+) was more common in CA than AA men (47% vs 22%, pprostate cancer molecular subtypes, and tumor location. Location-specific differences in androgen regulation may further underlie these relationships. Copyright © 2015. Published by Elsevier B.V.

  17. Potential of luminescence based molecular animal imaging in research areas pertaining to cancer biology and therapy

    International Nuclear Information System (INIS)

    Yadav, Hansa D.; Shetake, Neena G.; Balla Murali, M.S.; Kumar, Amit; Pandey, B.N.

    2017-01-01

    Animal imaging is getting tremendous importance in biomedical research areas including drug delivery, radiobiology and cancer research. Even though, imaging techniques like CT, PET, SPECT, MRI are available for experimental animals, luminescence-based molecular imaging is still considered as crucial and common tool for biomedical laboratories due to easy handling/maintenance, cost effectiveness and various strategies available to manipulate the molecules/cells employed for imaging purposes. The Molecular Animal Imaging System available in our laboratory is being utilized for various cancer research activities including measurement of tumor growth kinetics, angiogenesis, therapeutic efficacy evaluation and metastasis studies. Moreover, the imaging system is also been used for radio-luminescence imaging based on Cherenkov radiation of radio-pharmaceuticals. (author)

  18. Harnessing Preclinical Molecular Imaging to Inform Advances in Personalized Cancer Medicine.

    Science.gov (United States)

    Clark, Peter M; Ebiana, Victoria A; Gosa, Laura; Cloughesy, Timothy F; Nathanson, David A

    2017-05-01

    Comprehensive molecular analysis of individual tumors provides great potential for personalized cancer therapy. However, the presence of a particular genetic alteration is often insufficient to predict therapeutic efficacy. Drugs with distinct mechanisms of action can affect the biology of tumors in specific and unique ways. Therefore, assays that can measure drug-induced perturbations of defined functional tumor properties can be highly complementary to genomic analysis. PET provides the capacity to noninvasively measure the dynamics of various tumor biologic processes in vivo. Here, we review the underlying biochemical and biologic basis for a variety of PET tracers and how they may be used to better optimize cancer therapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  19. Molecular Modification of Metadherin/MTDH Impacts the Sensitivity of Breast Cancer to Doxorubicin.

    Directory of Open Access Journals (Sweden)

    Zhenchuan Song

    Full Text Available Breast cancer is a leading cause of death in women and with an increasing worldwide incidence. Doxorubicin, as a first-line anthracycline-based drug is conventional used on breast cancer clinical chemotherapy. However, the drug resistances limited the curative effect of the doxorubicin therapy in breast cancer patients, but the molecular mechanism determinants of breast cancer resistance to doxorubicin chemotherapy are not fully understood. In order to explore the association between metadherin (MTDH and doxorubicin sensitivity, the differential expressions of MTDH in breast cancer cell lines and the sensitivity to doxorubicin of breast cancer cell lines were investigated.The mRNA and protein expression of MTDH were determined by real-time PCR and Western blot in breast cancer cells such as MDA-MB-231, MCF-7, MDA-MB-435S, MCF-7/ADR cells. Once MTDH gene was knocked down by siRNA in MCF-7/ADR cells and overexpressed by MTDH plasmid transfection in MDA-MB-231 cells, the cell growth and therapeutic sensitivity of doxorubicin were evaluated using MTT and the Cell cycle assay and apoptosis rate was determined by flow cytometry.MCF-7/ADR cells revealed highly expressed MTDH and MDA-MB-231 cells had the lowest expression of MTDH. After MTDH gene was knocked down, the cell proliferation was inhibited, and the inhibitory rate of cell growth and apoptosis rate were enhanced, and the cell cycle arrest during the G0/G1 phase in the presence of doxorubicin treatment. On the other hand, the opposite results were observed in MDA-MB-231 cells with overexpressed MTDH gene.MTDH gene plays a promoting role in the proliferation of breast cancer cells and its high expression may be associated with doxorubicin sensitivity of breast cancer.

  20. Bitter melon juice targets molecular mechanisms underlying gemcitabine resistance in pancreatic cancer cells

    OpenAIRE

    SOMASAGARA, RANGANATHA R.; DEEP, GAGAN; SHROTRIYA, SANGEETA; PATEL, MANISHA; AGARWAL, CHAPLA; AGARWAL, RAJESH

    2015-01-01

    Pancreatic cancer (PanC) is one of the most lethal malignancies, and resistance towards gemcitabine, the front-line chemotherapy, is the main cause for dismal rate of survival in PanC patients; overcoming this resistance remains a major challenge to treat this deadly malignancy. Whereas several molecular mechanisms are known for gemcitabine resistance in PanC cells, altered metabolism and bioenergetics are not yet studied. Here, we compared metabolic and bioenergetic functions between gemcita...

  1. Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of the Most Aggressive Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Moira Ragazzi

    2014-01-01

    Full Text Available Anaplastic thyroid carcinoma (ATC is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features.

  2. Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.

    Science.gov (United States)

    Tothill, Richard W; Tinker, Anna V; George, Joshy; Brown, Robert; Fox, Stephen B; Lade, Stephen; Johnson, Daryl S; Trivett, Melanie K; Etemadmoghadam, Dariush; Locandro, Bianca; Traficante, Nadia; Fereday, Sian; Hung, Jillian A; Chiew, Yoke-Eng; Haviv, Izhak; Gertig, Dorota; DeFazio, Anna; Bowtell, David D L

    2008-08-15

    The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance.

  3. Dynamic fluorescence imaging with molecular agents for cancer detection

    Science.gov (United States)

    Kwon, Sun Kuk

    Non-invasive dynamic optical imaging of small animals requires the development of a novel fluorescence imaging modality. Herein, fluorescence imaging is demonstrated with sub-second camera integration times using agents specifically targeted to disease markers, enabling rapid detection of cancerous regions. The continuous-wave fluorescence imaging acquires data with an intensified or an electron-multiplying charge-coupled device. The work presented in this dissertation (i) assessed dose-dependent uptake using dynamic fluorescence imaging and pharmacokinetic (PK) models, (ii) evaluated disease marker availability in two different xenograft tumors, (iii) compared the impact of autofluorescence in fluorescence imaging of near-infrared (NIR) vs. red light excitable fluorescent contrast agents, (iv) demonstrated dual-wavelength fluorescence imaging of angiogenic vessels and lymphatics associated with a xenograft tumor model, and (v) examined dynamic multi-wavelength, whole-body fluorescence imaging with two different fluorescent contrast agents. PK analysis showed that the uptake of Cy5.5-c(KRGDf) in xenograft tumor regions linearly increased with doses of Cy5.5-c(KRGDf) up to 1.5 nmol/mouse. Above 1.5 nmol/mouse, the uptake did not increase with doses, suggesting receptor saturation. Target to background ratio (TBR) and PK analysis for two different tumor cell lines showed that while Kaposi's sarcoma (KS1767) exhibited early and rapid uptake of Cy5.5-c(KRGDf), human melanoma tumors (M21) had non-significant TBR differences and early uptake rates similar to the contralateral normal tissue regions. The differences may be due to different compartment location of the target. A comparison of fluorescence imaging with NIR vs. red light excitable fluorescent dyes demonstrates that NIR dyes are associated with less background signal, enabling rapid tumor detection. In contrast, animals injected with red light excitable fluorescent dyes showed high autofluorescence. Dual

  4. Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms.

    Science.gov (United States)

    Sinha, Dona; Sarkar, Nivedita; Biswas, Jaydip; Bishayee, Anupam

    2016-10-01

    Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved problems with metastatic breast cancer is recurrence after receiving objective response to chemotherapy, drug-induced side effects of first line chemotherapy and delayed response to second line of treatment. Unfortunately, very few options are available as third line treatment. It is clear that under such circumstances there is an urgent need for new and effective drugs. Phytochemicals are among the most promising chemopreventive treatment options for the management of cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a non-flavonoid polyphenol present in several dietary sources, including grapes, berries, soy beans, pomegranate and peanuts, has been shown to possess a wide range of health benefits through its effect on a plethora of molecular targets.The present review encompasses the role of resveratrol and its natural/synthetic analogue in the light of their efficacy against tumor cell proliferation, metastasis, epigenetic alterations and for induction of apoptosis as well as sensitization toward chemotherapeutic drugs in various in vitro and in vivo models of breast cancer. The roles of resveratrol as a phytoestrogen, an aromatase inhibitor and in stem cell therapy as well as adjuvent treatment are also discussed. This review explores the full potential of resveratrol in breast cancer prevention and treatment with current limitations, challenges and future directions of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Molecular Features of Subtype-Specific Progression from Ductal Carcinoma In Situ to Invasive Breast Cancer

    Directory of Open Access Journals (Sweden)

    Robert Lesurf

    2016-07-01

    Full Text Available Breast cancer consists of at least five main molecular “intrinsic” subtypes that are reflected in both pre-invasive and invasive disease. Although previous studies have suggested that many of the molecular features of invasive breast cancer are established early, it is unclear what mechanisms drive progression and whether the mechanisms of progression are dependent or independent of subtype. We have generated mRNA, miRNA, and DNA copy-number profiles from a total of 59 in situ lesions and 85 invasive tumors in order to comprehensively identify those genes, signaling pathways, processes, and cell types that are involved in breast cancer progression. Our work provides evidence that there are molecular features associated with disease progression that are unique to the intrinsic subtypes. We additionally establish subtype-specific signatures that are able to identify a small proportion of pre-invasive tumors with expression profiles that resemble invasive carcinoma, indicating a higher likelihood of future disease progression.

  6. [Application of molecular diagnostic techniques in precision medicine of personalized treatment for colorectal cancer].

    Science.gov (United States)

    Fu, Ji; Lin, Guole

    2016-01-01

    Precision medicine is to customize the treatment options for individual patient based on the personal genome information. Colorectal cancer (CRC) is one of the most common cancer worldwide. Molecular heterogeneity of CRC, which includes the MSI phenotype, hypermutation phenotype, and their relationship with clinical preferences, is believed to be one of the main factors responsible for the considerable variability in treatment response. The development of powerful next-generation sequencing (NGS) technologies allows us to further understand the biological behavior of colorectal cancer, and to analyze the prognosis and chemotherapeutic drug reactions by molecular diagnostic techniques, which can guide the clinical treatment. This paper will introduce the new findings in this field. Meanwhile we integrate the new progress of key pathways including EGFR, RAS, PI3K/AKT and VEGF, and the experience in selective patients through associated molecular diagnostic screening who gain better efficacy after target therapy. The technique for detecting circulating tumor DNA (ctDNA) is introduced here as well, which can identify patients with high risk for recurrence, and demonstrate the risk of chemotherapy resistance. Mechanism of tumor drug resistance may be revealed by dynamic observation of gene alteration during treatment.

  7. Proteomics Characterization of the Molecular Mechanisms of Mutant P53 Reactivation with PRIMA-1 in Breast Cancer Cells

    National Research Council Canada - National Science Library

    Daoud, Sayed S

    2006-01-01

    The main purpose of the study is to identify novel protein-protein interactions in various locations of cells to establish the molecular mechanisms of mutant p53 reactivation with PRIMA-1 in breast cancer cells...

  8. Gastrointestinal metastasis from primary lung cancer. Case series and systematic literature review.

    Science.gov (United States)

    Balla, Andrea; D Subiela, José; Bollo, Jesús; Martínez, Carmen; Rodriguez Luppi, Carlos; Hernández, Pilar; Pascual-González, Yuliana; Quaresima, Silvia; M Targarona, Eduard

    2018-04-01

    Aim of the present study is to report clinical characteristics and outcomes of patients treated in authors' hospital for GI metastasis from primary lung cancer, and to report and analyse the same data concerning patients retrieved from a systematic literature review. We performed a retrospective analysis of prospectively collected data, and a systematic review using the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Ninety-one patients were included, 5 patients from the authors' hospital and 86 through PubMed database using the keywords "intestinal metastasis" AND "lung cancer". The median time between primary lung cancer diagnosis and GI metastasis diagnosis was 2 months and the median overall survival was 4 months. This group of patients present a poor prognosis and the gold standard treatment is not defined. None of the reported treatments had a significant impact on survival. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. End-of-Life Care for Blood Cancers: A Series of Focus Groups With Hematologic Oncologists

    Science.gov (United States)

    Odejide, Oreofe O.; Salas Coronado, Diana Y.; Watts, Corey D.; Wright, Alexi A.; Abel, Gregory A.

    2014-01-01

    Purpose: Hematologic cancers are associated with aggressive cancer-directed care near death and underuse of hospice and palliative care services. We sought to explore hematologic oncologists' perspectives and decision-making processes regarding end-of-life (EOL) care. Methods: Between September 2013 and January 2014, 20 hematologic oncologists from the Dana-Farber/Harvard Cancer Center participated in four focus groups regarding EOL care for leukemia, lymphoma, multiple myeloma, and hematopoietic stem-cell transplantation. Focus groups employed a semistructured format with case vignettes and open-ended questions and were followed by thematic analysis. Results: Many participants felt that identifying the EOL phase for patients with hematologic cancers was challenging as a result of the continuing potential for cure with advanced disease and the often rapid pace of decline near death. This difficulty was reported to result in later initiation of EOL care. Barriers to high-quality EOL care were also reported to be multifactorial, including unrealistic expectations from both physicians and patients, long-term patient-physician relationships resulting in difficulty conducting EOL discussions, and inadequacy of existing home-based EOL services. Participants also expressed concern that some EOL quality measures developed for solid tumors may be unacceptable for patients with blood cancers given their unique needs at the EOL (eg, palliative transfusions). Conclusion: Our analysis suggests that hematologic oncologists need better clinical markers for when to initiate EOL care. In addition, current quality measures may be inappropriate for identifying overly aggressive care for patients with blood cancers. Further research is needed to develop effective interventions to improve EOL care for this patient population. PMID:25294393

  10. Computational design of new molecular scaffolds for medicinal chemistry, part II: generalization of analog series-based scaffolds

    Science.gov (United States)

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2018-01-01

    Aim: Extending and generalizing the computational concept of analog series-based (ASB) scaffolds. Materials & methods: Methodological modifications were introduced to further increase the coverage of analog series (ASs) and compounds by ASB scaffolds. From bioactive compounds, ASs were systematically extracted and second-generation ASB scaffolds isolated. Results: More than 20,000 second-generation ASB scaffolds with single or multiple substitution sites were extracted from active compounds, achieving more than 90% coverage of ASs. Conclusion: Generalization of the ASB scaffold approach has yielded a large knowledge base of scaffold-capturing compound series and target information. PMID:29379641

  11. Crosstalk between Apoptosis and Autophagy: Molecular Mechanisms and Therapeutic Strategies in Cancer

    Directory of Open Access Journals (Sweden)

    Abdelouahid El-Khattouti

    2013-01-01

    Full Text Available Both apoptosis and autophagy are highly conserved processes that besides their role in the maintenance of the organismal and cellular homeostasis serve as a main target of tumor therapeutics. Although their important roles in the modulation of tumor therapeutic strategies have been widely reported, the molecular actions of both apoptosis and autophagy are counteracted by cancer protective mechanisms. While apoptosis is a tightly regulated process that is implicated in the removal of damaged or unwanted cells, autophagy is a cellular catabolic pathway that is involved in lysosomal degradation and recycling of proteins and organelles, and thereby is considered an important survival/protective mechanism for cancer cells in response to metabolic stress or chemotherapy. Although the relationship between autophagy and cell death is very complicated and has not been characterized in detail, the molecular mechanisms that control this relationship are considered to be a relevant target for the development of a therapeutic strategy for tumor treatment. In this review, we focus on the molecular mechanisms of apoptosis, autophagy, and those of the crosstalk between apoptosis and autophagy in order to provide insight into the molecular mechanisms that may be essential for the balance between cell survival and death as well as their role as targets for the development of novel therapeutic approaches.

  12. [Molecular classification of breast cancer patients obtained through the technique of chromogenic in situ hybridization (CISH)].

    Science.gov (United States)

    Fernández, Angel; Reigosa, Aldo

    2013-12-01

    Breast cancer is a heterogeneous disease composed of a growing number of biological subtypes, with substantial variability of the disease progression within each category. The aim of this research was to classify the samples object of study according to the molecular classes of breast cancer: luminal A, luminal B, HER2 and triple negative, as a result of the state of HER2 amplification obtained by the technique of chromogenic in situ hybridization (CISH). The sample consisted of 200 biopsies fixed in 10% formalin, processed by standard techniques up to paraffin embedding, corresponding to patients diagnosed with invasive ductal carcinoma of the breast. These biopsies were obtained from patients from private practice and the Institute of Oncology "Dr. Miguel Pérez Carreño", for immunohistochemistry (IHC) of hormone receptors and HER2 made in the Hospital Metropolitano del Norte, Valencia, Venezuela. The molecular classification of the patient's tumors considering the expression of estrogen and progesterone receptors by IHC and HER2 amplification by CISH, allowed those cases originally classified as unknown, since they had an indeterminate (2+) outcome for HER2 expression by IHC, to be grouped into the different molecular classes. Also, this classification permitted that some cases, initially considered as belonging to a molecular class, were assigned to another class, after the revaluation of the HER2 status by CISH.

  13. New insights into molecular diagnostic pathology of primary liver cancer: Advances and challenges.

    Science.gov (United States)

    Cong, Wen-Ming; Wu, Meng-Chao

    2015-11-01

    Primary liver cancer (PLC) is one of the most common malignancies worldwide with increasing incidence and accounts for the third leading cause of cancer-related mortality. Traditional morphopathology primarily emphasizes qualitative diagnosis of PLC, which is not sufficient to resolve the major concern of increasing the long-term treatment efficacy of PLC in clinical management for the modern era. Since the beginning of the 21st century, molecular pathology has played an active role in the investigation of the evaluation of the metastatic potential of PLC, detection of drug targets, prediction of recurrence risks, analysis of clonal origins, evaluation of the malignancy trend of precancerous lesions, and determination of clinical prognosis. As a result, many new progresses have been obtained, and new strategies of molecular-pathological diagnosis have been formed. Moreover, the new types of pathobiological diagnosis indicator systems for PLC have been preliminarily established. These achievements provide valuable molecular pathology-based guide for clinical formulation of individualized therapy programs for PLC. This review article briefly summarizes some relevant progresses of molecular-pathological diagnosis of PLC from the perspective of clinical translational application other than basic experimental studies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Long-term Survival of Personalized Surgical Treatment of Locally Advanced Non-small Cell Lung Cancer Based on Molecular Staging

    Directory of Open Access Journals (Sweden)

    Qinghua ZHOU

    2011-02-01

    Full Text Available Background and objective Approximately 35%-40% of patients with newly diagnosed non-small cell Lung cancer have locally advanced disease. The average survival time of these patients only have 6-8 months with chemotherapy. The aim of this study is to explore and summarize the probability of detection of micrometastasis in peripheral blood for molecular staging, and for selection of indication of surgical treatment, and beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in locally advanced lung cancer; to summarize the long-time survival result of personalized surgical treatment of 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Methods CK19 mRNA expression of peripheral blood samples was detected in 516 lung cancer patients by RT-PCR before operation for molecular diagnosis of micrometastasis, personalized molecular staging, and for selection of indication of surgical treatment and the beneficiary of neoadjuvant chemotherapy and postoperative adjuvant therapy in patients with locally advanced nonsmall cell lung cancer invaded heart, great vessels or both. The long-term survival result of personalized surgical treatment was retrospectively analyzed in 516 patients with locally advanced non-small cell lung cancer based on molecular staging methods. Results There were 322 patients with squamous cell carcinoma and 194 cases with adenocarcinoma in the series of 516 patients with locally advanced lung cancer involved heart, great vessels or both. There were 112 patients with IIIA disease and 404 cases with IIIB disease according to P-TNM staging. There were 97 patients with M-IIIA disease, 278 cases with M-IIIB disease and 141 cases with III disease according to our personalized molecular staging. Of the 516 patients, bronchoplastic procedures and pulmonary artery reconstruction was carried out in 256 cases; lobectomy combined with resection and reconstruction of partial left

  15. Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets.

    Directory of Open Access Journals (Sweden)

    David Britton

    Full Text Available LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application.Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12, were labelled with tandem mass tags (TMT 8-plex, separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological events from the complex dataset.Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1, but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites, 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold in different cases highlighting their predictive power.Here we provided critical information enabling us to identify the common and unique molecular events likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.

  16. Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets.

    Science.gov (United States)

    Britton, David; Zen, Yoh; Quaglia, Alberto; Selzer, Stefan; Mitra, Vikram; Löβner, Christopher; Jung, Stephan; Böhm, Gitte; Schmid, Peter; Prefot, Petra; Hoehle, Claudia; Koncarevic, Sasa; Gee, Julia; Nicholson, Robert; Ward, Malcolm; Castellano, Leandro; Stebbing, Justin; Zucht, Hans Dieter; Sarker, Debashis; Heaton, Nigel; Pike, Ian

    2014-01-01

    LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application. Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12), were labelled with tandem mass tags (TMT 8-plex), separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological events from the complex dataset. Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1), but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites), 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα) and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold) in different cases highlighting their predictive power. Here we provided critical information enabling us to identify the common and unique molecular events likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.

  17. Final Validation of the ProMisE Molecular Classifier for Endometrial Carcinoma in a Large Population-based Case Series.

    Science.gov (United States)

    Kommoss, S; McConechy, M K; Kommoss, F; Leung, S; Bunz, A; Magrill, J; Britton, H; Kommoss, F; Grevenkamp, F; Karnezis, A; Yang, W; Lum, A; Krämer, B; Taran, F; Staebler, A; Lax, S; Brucker, S Y; Huntsman, D G; Gilks, C B; McAlpine, J N; Talhouk, A

    2018-02-07

    Based on The Cancer Genome Atlas, we previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). ProMisE identifies four prognostically distinct molecular subtypes, and can be applied to diagnostic specimens (biopsy/curettings), enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier prior to clinical application. We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003-13. Primary outcomes of overall, disease-specific and progression-free survival were evaluated for clinical, pathological, and molecular features. Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 - 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB (89 (19.7%)), stage II (26 (5.8%)), and stage III/IV (61 (13.5%)). ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognostic marker for progression-free (P=0.001) and disease-specific (P=0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, kappa 0.88. We have developed, confirmed and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM

  18. Bases moleculares del cáncer colorrectal = Molecular bases of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Muñetón Peña, Carlos Mario

    2012-04-01

    Full Text Available Se considera que el cáncer colorrectal (CCR es un problema mundial de salud pública; es el tercer cáncer más común en hombres y el segundo en mujeres. Su distribución geográfica es variable: las tasas de incidencia son altas en países desarrollados de Europa, Norteamérica y Oceanía y bajas en países de regiones subdesarrolladas como África y Suramérica. Sin embargo, los datos de estudios recientes publicados por la Agencia Internacional de Investigaciones en Cáncer (IARC, International Agency for Research on Cancer muestran un aumento rápido en la incidencia de CCR en los períodos 1983-1987 y 1998-2002 en países en vías de desarrollo (1, mientras que en países desarrollados la incidencia se ha estabilizado y en muchos casos ha disminuido (2. La carcinogénesis del CCR es un proceso de múltiples etapas, caracterizado por una gran inestabilidad genómica que permite la acumulación de mutaciones en protoncogenes y genes supresores de tumores, alteración en la expresión de genes y producción de proteínas no funcionales, que les confieren a las células ventajas de proliferación y aumento de la supervivencia. La inestabilidad genómica del CCR se produce por diferentes vías; entre las más importantes se encuentran: la de inestabilidad cromosómica (CIN, la de inestabilidad microsatelital (MSI y la de metilación.

  19. [Personalized molecular medicine: new paradigms in the treatment of cochlear implant and cancer patients].

    Science.gov (United States)

    Zenner, H P; Pfister, M; Friese, N; Zrenner, E; Röcken, M

    2014-07-01

    To evaluate present options for the indication of cochlear implants (CI) and new forms of treatment for head and neck cancer, melanomas and basal cell carcinomas, with emphasis on future perspectives. A literature search was performed in the PubMed database. Search parameters were "personalized medicine", "individualized medicine" and "molecular medicine". Personalized medicine based on molecular-genetic evaluation of functional proteins such as otoferlin, connexin 26 and KCNQ4 or the Usher gene is becoming increasingly important for the indication of CI in the context of infant deafness. Determination of HER2/EGFR mutations in the epithelial growth factor receptor (EGFR) gene may be an important prognostic parameter for therapeutic decisions in head and neck cancer patients. In basal cell carcinoma therapy, mutations in the Hedgehog (PCTH1) and Smoothened (SMO) pathways strongly influence the indication of therapeutic Hedgehog inhibition, e.g. using small molecules. Analyses of c-Kit receptor, BRAF-600E and NRAS mutations are required for specific molecular therapy of metastasizing melanomas. The significant advances in the field of specific molecular therapy are best illustrated by the availability of the first gene therapeutic procedures for treatment of RPE65-induced infantile retinal degradation. The aim of personalized molecular medicine is to identify patients who will respond particularly positively or negatively (e.g. in terms of adverse side effects) to a therapy using the methods of molecular medicine. This should allow a specific therapy to be successfully applied or preclude its indication in order to avoid serious adverse side effects. This approach serves to stratify patients for adequate treatment.

  20. Prostate cancer detection from model-free T1-weighted time series and diffusion imaging

    Science.gov (United States)

    Haq, Nandinee F.; Kozlowski, Piotr; Jones, Edward C.; Chang, Silvia D.; Goldenberg, S. Larry; Moradi, Mehdi

    2015-03-01

    The combination of Dynamic Contrast Enhanced (DCE) images with diffusion MRI has shown great potential in prostate cancer detection. The parameterization of DCE images to generate cancer markers is traditionally performed based on pharmacokinetic modeling. However, pharmacokinetic models make simplistic assumptions about the tissue perfusion process, require the knowledge of contrast agent concentration in a major artery, and the modeling process is sensitive to noise and fitting instabilities. We address this issue by extracting features directly from the DCE T1-weighted time course without modeling. In this work, we employed a set of data-driven features generated by mapping the DCE T1 time course to its principal component space, along with diffusion MRI features to detect prostate cancer. The optimal set of DCE features is extracted with sparse regularized regression through a Least Absolute Shrinkage and Selection Operator (LASSO) model. We show that when our proposed features are used within the multiparametric MRI protocol to replace the pharmacokinetic parameters, the area under ROC curve is 0.91 for peripheral zone classification and 0.87 for whole gland classification. We were able to correctly classify 32 out of 35 peripheral tumor areas identified in the data when the proposed features were used with support vector machine classification. The proposed feature set was used to generate cancer likelihood maps for the prostate gland.

  1. Annexin A1 expression in a pooled breast cancer series : Association with tumor subtypes and prognosis

    NARCIS (Netherlands)

    Sobral-Leite, Marcelo; Wesseling, Jelle; Smit, Vincent T H B M; Nevanlinna, Heli; van Miltenburg, Martine H.; Sanders, Joyce; Hofland, Ingrid; Blows, Fiona M.; Coulson, Penny; Patrycja, Gazinska; Schellens, Jan H M; Fagerholm, Rainer; Heikkilä, Päivi; Aittomäki, Kristiina; Blomqvist, Carl; Provenzano, Elena; Ali, Hamid Raza; Figueroa, Jonine; Sherman, Mark; Lissowska, Jolanta; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli Matti; Hartikainen, Jaana M.; Phillips, Kelly Anne; Couch, Fergus J.; Olson, Janet E.; Vachon, Celine; Visscher, Daniel; Brenner, Hermann; Butterbach, Katja; Arndt, Volker; Holleczek, Bernd; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W M; van Deurzen, Carolien H M; van de Water, Bob; Broeks, Annegien; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Easton, Douglas F.; Pharoah, Paul D P; García-Closas, Montserrat; de Graauw, Marjo; Schmidt, Marjanka K.; Aghmesheh, Morteza; Amor, David; Andrews, Lesley; Antill, Yoland; Armitage, Shane; Arnold, Leanne; Balleine, Rosemary; Bankier, Agnes; Bastick, Patti; Beesley, Jonathan; Beilby, John; Bennett, Barbara; Bennett, Ian; Berry, Geoffrey; Blackburn, Anneke; Bogwitz, Michael; Brennan, Meagan; Brown, Melissa; Buckley, Michael; Burgess, Matthew; Burke, Jo; Butow, Phyllis; Byron, Keith; Callen, David; Campbell, Ian; Chauhan, Deepa; Chauhan, Manisha; Christian, Alice; Clarke, Christine; Colley, Alison; Cotton, Dick; Crook, Ashley; Cui, James; Culling, Bronwyn; Cummings, Margaret; Dawson, Sarah Jane; deFazio, Anna; Delatycki, Martin; Dickson, Rebecca; Dixon, Joanne; Dobrovic, Alexander; Dudding, Tracy; Edkins, Ted; Edwards, Stacey; Eisenbruch, Maurice; Farshid, Gelareh; Fawcett, Susan; Fellows, Andrew; Fenton, Georgina; Field, Michael; Firgaira, Frank; Flanagan, James; Fleming, Jean; Fong, Peter; Forbes, John; Fox, Stephen; French, Juliet; Friedlander, Michael; Gaff, Clara; Gardner, Mac; Gattas, Mike; George, Peter; Giles, Graham; Gill, Grantley; Goldblatt, Jack; Greening, Sian; Grist, Scott; Haan, Eric; Hardie, Kate; Harris, Marion; Hart, Stewart; Hayward, Nick; Healey, Sue; Heiniger, Louise; Hopper, John; Humphrey, Evelyn; Hunt, Clare; James, Paul; Jenkins, Mark; Jones, Alison; Kefford, Rick; Kidd, Alexa; Kiely, Belinda; Kirk, Judy; Koehler, Jessica; Kollias, James; Kovalenko, Serguei; Lakhani, Sunil; Leaming, Amanda; Leary, Jennifer; Lim, Jacqueline; Lindeman, Geoff; Lipton, Lara; Lobb, Liz; Mann, Graham; Marsh, Deborah; McLachlan, Sue Anne; Meiser, Bettina; Meldrum, Cliff; Milne, Roger; Mitchell, Gillian; Newman, Beth; Niedermayr, Eveline; Nightingale, Sophie; O'Connell, Shona; O'Loughlin, Imelda; Osborne, Richard; Pachter, Nick; Patterson, Briony; Peters, Lester; Phillips, Kelly; Price, Melanie; Purser, Lynne; Reeve, Tony; Reeve, Jeanne; Richards, Robert; Rickard, Edwina; Robinson, Bridget; Rudzki, Barney; Saleh, Mona; Salisbury, Elizabeth; Sambrook, Joe; Saunders, Christobel; Saunus, Jodi; Sayer, Robyn; Scott, Elizabeth; Scott, Rodney; Scott, Clare; Seshadri, Ram; Sexton, Adrienne; Sharma, Raghwa; Shelling, Andrew; Simpson, Peter; Southey, Melissa; Spurdle, Amanda; Suthers, Graeme; Sykes, Pamela; Tassell, Margaret; Taylor, Donna; Taylor, Jessica; Thierry, Benjamin; Thomas, Susan; Thompson, Ella; Thorne, Heather; Townshend, Sharron; Trainer, Alison; Tran, Lan; Tucker, Kathy; Tyler, Janet; Visvader, Jane; Walker, Logan; Walpole, Ian; Ward, Robin; Waring, Paul; Warner, Bev; Warren, Graham; Williams, Rachael; Wilson, Judy; Winship, Ingrid; Wu, Kathy; Young, Mary Ann; Bowtell, D.; Green, A.; Webb, P.; de Fazio, A.; Gertig, D.

    2015-01-01

    Background: Annexin A1 (ANXA1) is a protein related with the carcinogenesis process and metastasis formation in many tumors. However, little is known about the prognostic value of ANXA1 in breast cancer. The purpose of this study is to evaluate the association between ANXA1 expression, BRCA1/2

  2. Mutational profiles of breast cancer metastases from a rapid autopsy series reveal multiple evolutionary trajectories.

    Science.gov (United States)

    Avigdor, Bracha Erlanger; Cimino-Mathews, Ashley; DeMarzo, Angelo M; Hicks, Jessica L; Shin, James; Sukumar, Saraswati; Fetting, John; Argani, Pedram; Park, Ben H; Wheelan, Sarah J

    2017-12-21

    Heterogeneity within and among tumors in a metastatic cancer patient is a well-established phenomenon that may confound treatment and accurate prognosis. Here, we used whole-exome sequencing to survey metastatic breast cancer tumors from 5 patients in a rapid autopsy program to construct the origin and genetic development of metastases. Metastases were obtained from 5 breast cancer patients using a rapid autopsy protocol and subjected to whole-exome sequencing. Metastases were evaluated for sharing of somatic mutations, correlation of copy number variation and loss of heterozygosity, and genetic similarity scores. Pathological features of the patients' disease were assessed by immunohistochemical analyses. Our data support a monoclonal origin of metastasis in 3 cases, but in 2 cases, metastases arose from at least 2 distinct subclones in the primary tumor. In the latter 2 cases, the primary tumor presented with mixed histologic and pathologic features, suggesting early divergent evolution within the primary tumor with maintenance of metastatic capability in multiple lineages. We used genetic and histopathological evidence to demonstrate that metastases can be derived from a single or multiple independent clones within a primary tumor. This underscores the complexity of breast cancer clonal evolution and has implications for how best to determine and implement therapies for early- and late-stage disease.

  3. Cell Biology and Cancer. Grades 9-12. NIH Curriculum Supplement Series.

    Science.gov (United States)

    Biological Sciences Curriculum Study, Colorado Springs.

    This curriculum supplement guide brings the latest medical discoveries to classrooms. This module focuses on the objectives of introducing students to major concepts related to the development of cancer and its impacts, and developing an understanding of the relationship between biomedical research and personal and public health. This module…

  4. Cancer in human immunodeficiency virus-infected children : A case series from the Children's Cancer Group and the National Cancer Institute

    NARCIS (Netherlands)

    Granovsky, MO; Mueller, BU; Nicholson, HS; Rosenberg, PS; Rabkin, CS

    Purpose: To describe the spectrum of malignancies in human immunodeficiency virus (HIV)-infected children and the clinical outcome of patients with these tumors. Methods: We retrospectively surveyed the Children's Cancer Group (CCG) and the National Cancer institute (NCI) for cases of cancer that

  5. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Feng-Yang, E-mail: fyzheng16@fudan.edu.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Lu, Qing, E-mail: lu.qing@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Huang, Bei-Jian, E-mail: huang.beijian@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Xia, Han-Sheng, E-mail: zs12036@126.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Yan, Li-Xia, E-mail: dndyanlixia@163.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Xi, E-mail: wang.xi@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Yuan, Wei, E-mail: yuan.wei@zs-hospital.sh.cn [Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Wen-Ping, E-mail: wang.wenping@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China)

    2017-01-15

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n = 128) were retraction phenomenon (odds ratio [OR] = 10.188), post-acoustic shadowing (OR = 5.112), and echogenic halo (OR = 3.263, P < 0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n = 39) were calcifications (OR = 6.210), absence of retraction phenomenon (OR = 4.375), non-mass lesions (OR = 4.286, P < 0.001), absence of echogenic halo (OR = 3.851, P = 0.035), and post-acoustic enhancement (OR = 3.641, P = 0.008). The predictors for the Triple-Negative subtype (n = 47) were absence of retraction phenomenon (OR = 5.884), post-acoustic enhancement (OR = 5.255, P < 0.001), absence of echogenic halo (OR = 4.138, P = 0.002), and absence of calcifications (OR = 3.363, P = 0.001). Predictors for the Luminal-B subtype (n = 89) had a relatively lower association (OR ≤ 2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for

  6. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    International Nuclear Information System (INIS)

    Zheng, Feng-Yang; Lu, Qing; Huang, Bei-Jian; Xia, Han-Sheng; Yan, Li-Xia; Wang, Xi; Yuan, Wei; Wang, Wen-Ping

    2017-01-01

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype