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Sample records for cancer integrating short

  1. A New View of Radiation-Induced Cancer: Integrating Short- and Long-Term Processes. Part II: Second Cancer Risk Estimation

    Science.gov (United States)

    Shuryak, Igor; Brenner, David J.; Hahnfeldt, Philip; Hlatky, Lynn; Sachs, Rainer K.

    2009-01-01

    As the number of cancer survivors grows, prediction of radiotherapy-induced second cancer risks becomes increasingly important. Because the latency period for solid tumors is long, the risks of recently introduced radiotherapy protocols are not yet directly measurable. In the accompanying article, we presented a new biologically based mathematical model, which, in principle, can estimate second cancer risks for any protocol. The novelty of the model is that it integrates, into a single formalism, mechanistic analyses of pre-malignant cell dynamics on two different time scales: short-term during radiotherapy and recovery; long-term during the entire life span. Here, we apply the model to nine solid cancer types (stomach, lung, colon, rectal, pancreatic, bladder, breast, central nervous system, and thyroid) using data on radiotherapy-induced second malignancies, on Japanese atomic bomb survivors, and on background US cancer incidence. Potentially, the model can be incorporated into radiotherapy treatment planning algorithms, adding second cancer risk as an optimization criterion.

  2. A new view of radiation-induced cancer: integrating short- and long-term processes. Part II: second cancer risk estimation

    OpenAIRE

    Shuryak, Igor; Hahnfeldt, Philip; Hlatky, Lynn; Sachs, Rainer K.; David J Brenner

    2009-01-01

    As the number of cancer survivors grows, prediction of radiotherapy-induced second cancer risks becomes increasingly important. Because the latency period for solid tumors is long, the risks of recently introduced radiotherapy protocols are not yet directly measurable. In the accompanying article, we presented a new biologically based mathematical model, which, in principle, can estimate second cancer risks for any protocol. The novelty of the model is that it integrates, into a single formal...

  3. Short-term effects of ultrahigh concentration cationic silica nanoparticles on cell internalization, cytotoxicity, and cell integrity with human breast cancer cell line (MCF-7)

    Energy Technology Data Exchange (ETDEWEB)

    Seog, Ji Hyun [Korea Advanced Institute of Science and Technology, Graduate School of Nanoscience and Technology (Korea, Republic of); Kong, Bokyung [Corning Precision Materials (Korea, Republic of); Kim, Dongheun [Korea Advanced Institute of Science and Technology, Graduate School of Nanoscience and Technology (Korea, Republic of); Graham, Lauren M. [University of Maryland, Department of Chemistry and Biochemistry (United States); Choi, Joon Sig [Chungnam National University, Department of Biochemistry (Korea, Republic of); Lee, Sang Bok, E-mail: slee@umd.edu [Korea Advanced Institute of Science and Technology, Graduate School of Nanoscience and Technology (Korea, Republic of)

    2015-01-15

    High concentrations of cationic colloidal silica nanoparticles (CCS-NPs) have been widely used for the enrichment of plasma membrane proteins. However, the interaction between the CCS-NPs and cells under the required concentration for the isolation of plasma membrane are rarely investigated. We evaluated the internalization and toxicity of the 15 nm CCS-NPs which were exposed at high concentrations with short time in human breast cancer cells (MCF-7) with transmission electron microscopy, energy dispersive X-ray spectroscopy, inductively coupled plasma atomic emission spectroscopy, and colorimetric assays. The NPs were observed throughout the cells, particularly in the cytoplasm and the nucleus, after short incubation periods. Additionally, the NPs significantly influenced the membrane integrity of the MCF-7 cells.

  4. Short course radiotherapy with simultaneous integrated boost for stage I-II breast cancer, early toxicities of a randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Van Parijs Hilde

    2012-06-01

    Full Text Available Abstract Background TomoBreast is a unicenter, non-blinded randomized trial comparing conventional radiotherapy (CR vs. hypofractionated Tomotherapy (TT for post-operative treatment of breast cancer. The purpose of the trial is to compare whether TT can reduce heart and pulmonary toxicity. We evaluate early toxicities. Methods The trial started inclusion in May 2007 and reached its recruitment in August 2011. Women with stage T1-3N0M0 or T1-2N1M0 breast cancer completely resected by tumorectomy (BCS or by mastectomy (MA who consented to participate were randomized, according to a prescribed computer-generated randomization schedule, between control arm of CR 25x2 Gy/5 weeks by tangential fields on breast/chest wall, plus supraclavicular-axillary field if node-positive, and sequential boost 8x2 Gy/2 weeks if BCS (cumulative dose 66 Gy/7 weeks, versus experimental TT arm of 15x2.8 Gy/3 weeks, including nodal areas if node-positive and simultaneous integrated boost of 0.6 Gy if BCS (cumulative dose 51 Gy/3 weeks. Outcomes evaluated were the pulmonary and heart function. Comparison of proportions used one-sided Fisher's exact test. Results By May 2010, 70 patients were randomized and had more than 1 year of follow-up. Out of 69 evaluable cases, 32 were assigned to CR (21 BCS, 11 MA, 37 to TT (20 BCS, 17 MA. Skin toxicity of grade ≥1 at 2 years was 60% in CR, vs. 30% in TT arm. Heart function showed no significant difference for left ventricular ejection fraction at 2 years, CR 4.8% vs. TT 4.6%. Pulmonary function tests at 2 years showed grade ≥1 decline of FEV1 in 21% of CR, vs. 15% of TT and decline of DLco in 29% of CR, vs. 7% of TT (P = 0.05. Conclusions There were no unexpected severe toxicities. Short course radiotherapy of the breast with simultaneous integrated boost over 3 weeks proved feasible without excess toxicities. Pulmonary tests showed a slight trend in favor of Tomotherapy, which will need

  5. Precursors of Short GRBs Registered by SPI-ACS/INTEGRAL

    Science.gov (United States)

    Minaev, P.; Pozanenko, A.

    2016-10-01

    We have searched for precursors in light curves of short gamma-ray bursts registered by SPI-ACS/INTEGRAL in 2002-2014. The portion of short bursts with precursor activity will be less than 0.4% from all short bursts registered by SPI-ACS.

  6. Short telomere length, cancer survival, and cancer risk in 47102 individuals

    DEFF Research Database (Denmark)

    Weischer, Maren; Nordestgaard, Børge G; Cawthon, Richard M;

    2013-01-01

    Recent meta-analyses have suggested that short telomere length was associated with increased risk of cancer. We therefore tested the hypotheses that short telomere length was associated with increased risk of cancer and with increased risk of early death after cancer.......Recent meta-analyses have suggested that short telomere length was associated with increased risk of cancer. We therefore tested the hypotheses that short telomere length was associated with increased risk of cancer and with increased risk of early death after cancer....

  7. Integrating yoga into cancer care.

    Science.gov (United States)

    DiStasio, Susan A

    2008-02-01

    Although yoga has been practiced in Eastern culture for thousands of years as part of life philosophy, classes in the United States only recently have been offered to people with cancer. The word yoga is derived from the Sanskrit root yuj, meaning to bind, join, and yoke. This reflection of the union of the body, mind, and spirit is what differentiates yoga from general exercise programs. Yoga classes in the United States generally consist of asanas (postures), which are designed to exercise every muscle, nerve, and gland in the body. The postures are combined with pranayama, or rhythmic control of the breath. As a complementary therapy, yoga integrates awareness of breath, relaxation, exercise, and social support--elements that are key to enhancing quality of life in patients with cancer. Yoga practice may assist cancer survivors in managing symptoms such as depression, anxiety, insomnia, pain, and fatigue. As with all exercise programs, participants need to be aware of potential risks and their own limitations. The purpose of this article is to familiarize nurses with yoga as a complementary therapy, including current research findings, types of yoga, potential benefits, safety concerns, teacher training, and ways to integrate yoga into cancer care.

  8. Short circuit analysis of distribution system with integration of DG

    DEFF Research Database (Denmark)

    Su, Chi; Liu, Zhou; Chen, Zhe;

    2014-01-01

    during both balanced and unbalanced faults. Major factors such as external grid short circuit power capacity, WT integration location, connection type of WT integration transformer are taken into account. In turn, the challenges brought to the protection system in the distribution network are presented...

  9. Improving Music Genre Classification by Short Time Feature Integration

    DEFF Research Database (Denmark)

    Meng, Anders; Ahrendt, Peter; Larsen, Jan

    . The problem of making new features on the larger time scale from the short-time features (feature integration) has only received little attention. This paper investigates different methods for feature integration (early information fusion) and late information fusion (assembling of probabilistic outputs...

  10. Improving Music Genre Classification by Short-Time Feature Integration

    DEFF Research Database (Denmark)

    Meng, Anders; Ahrendt, Peter; Larsen, Jan

    2005-01-01

    of seconds instead of milliseconds. The problem of making new features on the larger time scale from the short-time features (feature integration) has only received little attention. This paper investigates different methods for feature integration and late information fusion for music genre classification....... A new feature integration technique, the AR model, is proposed and seemingly outperforms the commonly used mean-variance features....

  11. Short-term outcomes following laparoscopic resection for colon cancer.

    LENUS (Irish Health Repository)

    Kavanagh, Dara O

    2011-03-01

    Laparoscopic resection for colon cancer has been proven to have a similar oncological efficacy compared to open resection. Despite this, it is performed by a minority of colorectal surgeons. The aim of our study was to evaluate the short-term clinical, oncological and survival outcomes in all patients undergoing laparoscopic resection for colon cancer.

  12. Integrative Cancer Therapies简介

    Institute of Scientific and Technical Information of China (English)

    李霄茜; 周庆

    2009-01-01

    @@ Integrative Cancer Therapies(.ISSN:1534-7354;e-ISSN:1552-695X)是由美国SAGE出版公司出版发行的一本国际性癌症治疗杂志.杂志的现任主编为美国芝加哥伊利诺斯大学癌症综合治疗研究所的Keith I.Block博士.该杂志为季刊,每年3、6、9、12月各出版一期.

  13. Pathobiology of cancer metastasis: a short account

    Directory of Open Access Journals (Sweden)

    Feller Liviu

    2012-06-01

    Full Text Available Abstract Cancer-initiating cells display aberrant functional and phenotypic characteristics of normal stem cells from which they evolved by accumulation of multiple cytogenetic and/or epigenetic alterations. Signal transduction pathways which are essential for normal stem cell function are abnormally expressed by cancer cells, with a cancer cell phenotype playing an essential role in cancerization and metastasis. Local tumour progression, metastasis and metastatic tumour growth are mediated by direct cell-to-cell and paracrine reciprocal interactions between cancer cells and various stromal cells including fibroblasts, macrophages, bone marrow derived stem cells and progenitor cells. These interactions mediate breakdown of basement membrane barriers and angiogenesis both locally at the invasive front of the primary tumour and at the distant metastatic site; attract primary tumour cells to the candidate metastatic site; and promote proliferation, survival and growth of primary tumour cells and of metastatic cells at their distant site. It is the purpose of this article to highlight the analogies between some of the genetic programs of normal stem cells, and of cancer cells participating in the process of metastasis.

  14. The epidemiology of long- and short-term cancer survivors

    DEFF Research Database (Denmark)

    Jarlbæk, Lene; Christensen, Linda; Bruera, Eduardo;

    2014-01-01

    Introduction. In this study, we present data from a population-based cohort of incident cancer patients separated in long- and short-term survivors. Our aim was to procure denominators for use in the planning of rehabilitation and palliative care programs. Material and methods. A registry......-linkage cohort study. All cancer patients, diagnosed from 1993 to 2003 from a 470 000 large population, were followed individually from diagnosis to death or until 31 December 2008. Long-term survivors lived five years or more after the time of the cancer diagnosis (TOCD). Short-term survivors died less than...... five years after TOCD. Results. The cohort comprised 24 162 incident cancer patients with 41% long-term survivors (N = 9813). Seventy percent of the cohort was 60 + years at TOCD. The 14 349 short-term survivors' median survival was 0.6 year, and 78% died less than two years after TOCD. A 12 years...

  15. The integrated proactive surveillance system for prostate cancer.

    Science.gov (United States)

    Wang, Haibin; Yatawara, Mahendra; Huang, Shao-Chi; Dudley, Kevin; Szekely, Christine; Holden, Stuart; Piantadosi, Steven

    2012-01-01

    In this paper, we present the design and implementation of the integrated proactive surveillance system for prostate cancer (PASS-PC). The integrated PASS-PC is a multi-institutional web-based system aimed at collecting a variety of data on prostate cancer patients in a standardized and efficient way. The integrated PASS-PC was commissioned by the Prostate Cancer Foundation (PCF) and built through the joint of efforts by a group of experts in medical oncology, genetics, pathology, nutrition, and cancer research informatics. Their main goal is facilitating the efficient and uniform collection of critical demographic, lifestyle, nutritional, dietary and clinical information to be used in developing new strategies in diagnosing, preventing and treating prostate cancer.The integrated PASS-PC is designed based on common industry standards - a three tiered architecture and a Service- Oriented Architecture (SOA). It utilizes open source software and programming languages such as HTML, PHP, CSS, JQuery, Drupal and MySQL. We also use a commercial database management system - Oracle 11g. The integrated PASS-PC project uses a "confederation model" that encourages participation of any interested center, irrespective of its size or location. The integrated PASS-PC utilizes a standardized approach to data collection and reporting, and uses extensive validation procedures to prevent entering erroneous data. The integrated PASS-PC controlled vocabulary is harmonized with the National Cancer Institute (NCI) Thesaurus. Currently, two cancer centers in the USA are participating in the integrated PASS-PC project.THE FINAL SYSTEM HAS THREE MAIN COMPONENTS: 1. National Prostate Surveillance Network (NPSN) website; 2. NPSN myConnect portal; 3. Proactive Surveillance System for Prostate Cancer (PASS-PC). PASS-PC is a cancer Biomedical Informatics Grid (caBIG) compatible product. The integrated PASS-PC provides a foundation for collaborative prostate cancer research. It has been built to

  16. Short-Termed Integrated Forecasting System: 1993 Model documentation report

    Energy Technology Data Exchange (ETDEWEB)

    1993-05-01

    The purpose of this report is to define the Short-Term Integrated Forecasting System (STIFS) and describe its basic properties. The Energy Information Administration (EIA) of the US Energy Department (DOE) developed the STIFS model to generate short-term (up to 8 quarters), monthly forecasts of US supplies, demands, imports exports, stocks, and prices of various forms of energy. The models that constitute STIFS generate forecasts for a wide range of possible scenarios, including the following ones done routinely on a quarterly basis: A base (mid) world oil price and medium economic growth. A low world oil price and high economic growth. A high world oil price and low economic growth. This report is written for persons who want to know how short-term energy markets forecasts are produced by EIA. The report is intended as a reference document for model analysts, users, and the public.

  17. Fully integrated, fully automated generation of short tandem repeat profiles

    Science.gov (United States)

    2013-01-01

    Background The generation of short tandem repeat profiles, also referred to as ‘DNA typing,’ is not currently performed outside the laboratory because the process requires highly skilled technical operators and a controlled laboratory environment and infrastructure with several specialized instruments. The goal of this work was to develop a fully integrated system for the automated generation of short tandem repeat profiles from buccal swab samples, to improve forensic laboratory process flow as well as to enable short tandem repeat profile generation to be performed in police stations and in field-forward military, intelligence, and homeland security settings. Results An integrated system was developed consisting of an injection-molded microfluidic BioChipSet cassette, a ruggedized instrument, and expert system software. For each of five buccal swabs, the system purifies DNA using guanidinium-based lysis and silica binding, amplifies 15 short tandem repeat loci and the amelogenin locus, electrophoretically separates the resulting amplicons, and generates a profile. No operator processing of the samples is required, and the time from swab insertion to profile generation is 84 minutes. All required reagents are contained within the BioChipSet cassette; these consist of a lyophilized polymerase chain reaction mix and liquids for purification and electrophoretic separation. Profiles obtained from fully automated runs demonstrate that the integrated system generates concordant short tandem repeat profiles. The system exhibits single-base resolution from 100 to greater than 500 bases, with inter-run precision with a standard deviation of ±0.05 - 0.10 bases for most alleles. The reagents are stable for at least 6 months at 22°C, and the instrument has been designed and tested to Military Standard 810F for shock and vibration ruggedization. A nontechnical user can operate the system within or outside the laboratory. Conclusions The integrated system represents the

  18. Integrative cancer epidemiology--the next generation.

    Science.gov (United States)

    Spitz, Margaret R; Caporaso, Neil E; Sellers, Thomas A

    2012-12-01

    We outline an integrative approach to extend the boundaries of molecular cancer epidemiology by integrating modern and rapidly evolving "omics" technologies into state-of-the-art molecular epidemiology. In this way, one can comprehensively explore the mechanistic underpinnings of epidemiologic observations in cancer risk and outcome. We highlight the exciting opportunities to collaborate across large observational studies and to forge new interdisciplinary collaborative ventures.

  19. Audiovisual integration facilitates monkeys' short-term memory.

    Science.gov (United States)

    Bigelow, James; Poremba, Amy

    2016-07-01

    Many human behaviors are known to benefit from audiovisual integration, including language and communication, recognizing individuals, social decision making, and memory. Exceptionally little is known about the contributions of audiovisual integration to behavior in other primates. The current experiment investigated whether short-term memory in nonhuman primates is facilitated by the audiovisual presentation format. Three macaque monkeys that had previously learned an auditory delayed matching-to-sample (DMS) task were trained to perform a similar visual task, after which they were tested with a concurrent audiovisual DMS task with equal proportions of auditory, visual, and audiovisual trials. Parallel to outcomes in human studies, accuracy was higher and response times were faster on audiovisual trials than either unisensory trial type. Unexpectedly, two subjects exhibited superior unimodal performance on auditory trials, a finding that contrasts with previous studies, but likely reflects their training history. Our results provide the first demonstration of a bimodal memory advantage in nonhuman primates, lending further validation to their use as a model for understanding audiovisual integration and memory processing in humans.

  20. Integrated Immunotherapy for Breast Cancer

    Science.gov (United States)

    2013-09-01

    CSF. J Clin Invest 117, 1902 (Jul, 2007). 32. H. Yamaguchi et al., Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus . J Leukoc Biol 83, 1300 (May, 2008). ...comprehensive and systematic manner is the underlying principle of my goal to develop ’rational combination immunotherapy’ for breast cancer, one

  1. Short-course palliative radiotherapy for uterine cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Hyun; Lee, Ju Hye; Ki, Yong Kan; Kim, Won Taek; Park, Dahl; Kim, Dong Won [Dept. of Radiation Oncology, Biomedical Research Institute, Pusan National University Hospital, Busan (Korea, Republic of); Nam, Ji Ho; Jeon, Sang Ho [Dept. of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2013-12-15

    The purpose of this retrospective study was to evaluate the efficacy and feasibility of short-course hypofractionated radiotherapy (RT) for the palliation of uterine cervical cancer. Seventeen patients with cancer of the uterine cervix, who underwent palliative hypofractionated 3-dimensional conformal radiotherapy between January 2002 and June 2012, were retrospectively analyzed. RT was delivered to symptomatic lesions (both the primary mass and/or metastatic regional lymph nodes). The total dose was 20 to 25 Gy (median, 25 Gy) in 5 Gy daily fractions. The median follow-up duration was 12.2 months (range, 4 to 24 months). The median survival time was 7.8 months (range, 4 to 24 months). Vaginal bleeding was the most common presenting symptom followed by pelvic pain (9 patients). The overall response rates were 93.8% and 66.7% for vaginal bleeding control and pelvic pain, respectively. Nine patients did not have any acute side effects and 7 patients showed minor gastrointestinal toxicity. Only 1 patient had grade 3 diarrhea 1 week after completion of treatment, which was successfully treated conservatively. Late complications occurred in 4 patients; however, none of these were of grade 3 or higher severity. Short-course hypofractionated RT was effective and well tolerated as palliative treatment for uterine cervical cancer.

  2. Cancer cachexia: towards integrated therapeutic interventions.

    Science.gov (United States)

    Molfino, Alessio; Formiconi, Alessandra; Rossi Fanelli, Filippo; Muscaritoli, Maurizio

    2014-10-01

    Biological treatments represent a novel approach to counteract cancer cachexia. Monoclonal antibodies targeting cytokines and molecules responsible for muscle wasting, with an anti-inflammatory effect, however, still have several limitations and need further clinical investigation. New research in this field will contribute to the better understanding of the multifactorial pathogenesis of cancer cachexia, while favoring the consolidation of multimodal preventive and therapeutic strategies encompassing nutritional and pharmacological treatments. New pharmacological therapies and conventional nutritional treatments will soon integrate in the 'parallel pathway', aimed at early recognition, prevention and treatment of the metabolic and nutritional derangements occurring in cancer. This will likely produce improvement in quality of life, tolerance to treatments and survival.

  3. Integrated Immunotherapy for Breast Cancer

    Science.gov (United States)

    2015-09-01

    myocardial infarction among apparently healthy men. Circulation 101, 1767 (Apr 18, 2000). 33. E. A. Rakha, Pitfalls in outcome prediction of breast...cancer patients at diagnosis IL-6 plasma levels have been shown to be elevated in advanced metastatic BC patients (15, 31). To investigate whether the...plasma from BC patients was collected at diagnosis prior to surgery or any therapy. Interestingly, we found that IL-6 plasma levels were not

  4. Integrated Immunotherapy for Breast Cancer

    Science.gov (United States)

    2014-09-01

    be cultured in calcium‐ free DMEM supplemented with 1% FBS, cholera toxin (10 ng/ml), bovine insulin (3 μg/ml), hydrocortisone (0.5 μg/ml), EGF and...regimens for induction of optimal anti-tumor immunity. Then we will determine the optimal time to administer these regimens during disease ...node status. Breast Cancer Res Treat 60, 227 (Apr, 2000). 4. H. E. Kohrt et al., Profile of immune cells in axillary lymph nodes predicts disease -free

  5. Short Polymer Modeling using Self-Consistent Integral Equation Method

    Science.gov (United States)

    Kim, Yeongyoon; Park, So Jung; Kim, Jaeup

    2014-03-01

    Self-consistent field theory (SCFT) is an excellent mean field theoretical tool for predicting the morphologies of polymer based materials. In the standard SCFT, the polymer is modeled as a Gaussian chain which is suitable for a polymer of high molecular weight, but not necessarily for a polymer of low molecular weight. In order to overcome this limitation, Matsen and coworkers have recently developed SCFT of discrete polymer chains in which one polymer is modeled as finite number of beads joined by freely jointed bonds of fixed length. In their model, the diffusion equation of the canonical SCFT is replaced by an iterative integral equation, and the full spectral method is used for the production of the phase diagram of short block copolymers. In this study, for the finite length chain problem, we apply pseudospectral method which is the most efficient numerical scheme to solve the iterative integral equation. We use this new numerical method to investigate two different types of polymer bonds: spring-beads model and freely-jointed chain model. By comparing these results with those of the Gaussian chain model, the influences on the morphologies of diblock copolymer melts due to the chain length and the type of bonds are examined. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (no. 2012R1A1A2043633).

  6. Integrative Medicine Program- MD Anderson Cancer Center

    Directory of Open Access Journals (Sweden)

    Richard T Lee

    2012-06-01

    Full Text Available The Integrative Medicine Program at MD Anderson Cancer Center was first established in 1998.  Our mission is to empower patients with cancer and their families to become active partners in their own physical, psycho-spiritual, and social health through personalized education and evidenced-based clinical care to optimize health, quality of life, and clinical outcomes across the cancer continuum.  The program consists of three main components: clinical care, research, and education.  The Integrative Medicine Center provides clinical services to patients through individual and group programs.  The clinical philosophy of the center is to work collaboratively with the oncology teams to build comprehensive and integrative care plans that are personalized, evidence-based, and safe with the goal of improving clinical outcomes.  The individual services comprise of integrative oncology consultation, acupuncture, meditation, music therapy, nutrition, and oncology massage.  The center also provides a variety of group programs including meditation, yoga, tai chi, cooking classes and others.  Over the past 13 years, over 70,000 patients and families have participated in services and programs offered by the center.  The research portfolio focuses on three main areas: mind-body interventions, acupuncture, and meditation.  This lecture will focus on providing an overview of the Integrative Medicine Program at MD Anderson with a focus on the clinical services provided.  Participants will learn about the integrative clinical model and how this is applied to the care of cancer patients at MD Anderson Cancer Center.  Current and future research topics will be discussed as well as patient cases.

  7. Graves' Disease that Developed Shortly after Surgery for Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Hea Min Yu

    2013-09-01

    Full Text Available Graves' disease is an autoimmune disorder that may present with various clinical manifestations of hyperthyroidism. Patients with Graves' disease have a greater number of thyroid nodules and a higher incidence of thyroid cancer compared with patients with normal thyroid activity. However, cases in which patients are diagnosed with recurrence of Graves' disease shortly after partial thyroidectomy for thyroid cancer are very rare. Here we report a case of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary thyroid cancer. In this case, the patient developed hyperthyroidism 9 months after right hemithyroidectomy, and antithyroglobulin autoantibody and thyroid stimulating hormone receptor stimulating autoantibody were positive. Therefore, we diagnosed Graves' disease on the basis of the laboratory test results and thyroid ultrasonography findings. The patient was treated with and maintained on antithyroid drugs. The mechanism of the recurrence of Graves' disease in this patient is still unclear. The mechanism may have been the improper response of the immune system after partial thyroidectomy. To precisely determine the mechanisms in Graves' disease after partial thyroidectomy, further studies based on a greater number of cases are needed.

  8. Integrated flora management and pest control in short rotation coppice

    Energy Technology Data Exchange (ETDEWEB)

    Sage, R.; Tucker, K. [Game Conservancy Trust (United Kingdom)

    1994-12-31

    Weeds and insect pests can reduce yields and hence the profitability of short rotation coppice crops. Control becomes prudent when the cost of controlling the pests is exceeded by the yield loss (the economic threshold). This frequently happens when establishing the crop because of weed competition. Economic yield losses due to insect pest damage and weed competition in established SRC plots are less obvious but probably still occur. Traditional methods of control using pesticides is often logistically difficult and expensive. However there may be opportunities for controlling pest populations through cultural practices as part of an Integrated Pest Management (IPM) strategy. Insect pests have a range of natural enemy species that could be encouraged through habitat and crop manipulations while the occurrence of weeds could be reduced by providing a ground cover of other less competitive plants. These cultural practices can lead to environmental benefits by reducing chemical applications and mechanical movements and increasing floral diversity, wildlife use and the landscape and amenity value of the crop. (Author)

  9. Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care

    Science.gov (United States)

    Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care, a 2010 workshop sponsored by the Epidemiology and Genomics Research Program.

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

    Directory of Open Access Journals (Sweden)

    Claudia Erika Hernández Patiño

    2013-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  12. Integrated genomic analysis of breast cancers.

    Science.gov (United States)

    Addou-Klouche, L; Adélaïde, J; Cornen, S; Bekhouche, I; Finetti, P; Guille, A; Sircoulomb, F; Raynaud, S; Bertucci, F; Birnbaum, D; Chaffanet, M

    2012-12-01

    Breast cancer is the most frequent and the most deadly cancer in women in Western countries. Different classifications of disease (anatomoclinical, pathological, prognostic, genetic) are used for guiding the management of patients. Unfortunately, they fail to reflect the whole clinical heterogeneity of the disease. Consequently, molecularly distinct diseases are grouped in similar clinical classes, likely explaining the different clinical outcome between patients in a given class, and the fact that selection of the most appropriate diagnostic or therapeutic strategy for each patient is not done accurately. Today, treatment is efficient in only 70.0-75.0% of cases overall. Our repertoire of efficient drugs is limited but is being expanded with the discovery of new molecular targets for new drugs, based on the identification of candidate oncogenes and tumor suppressor genes (TSG) functionally relevant in disease. Development of new drugs makes therapeutical decisions even more demanding of reliable classifiers and prognostic/predictive tests. Breast cancer is a complex, heterogeneous disease at the molecular level. The combinatorial molecular origin and the heterogeneity of malignant cells, and the variability of the host background, create distinct subgroups of tumors endowed with different phenotypic features such as response to therapy and clinical outcome. Cellular and molecular analyses can identify new classes biologically and clinically relevant, as well as provide new clinically relevant markers and targets. The various stages of mammary tumorigenesis are not clearly defined and the genetic and epigenetic events critical to the development and aggressiveness of breast cancer are not precisely known. Because the phenotype of tumors is dependent on many genes, a large-scale and integrated molecular characterization of the genetic and epigenetic alterations and gene expression deregulation should allow the identification of new molecular classes clinically

  13. Integrated Large-Scale Environmental Information Systems: A Short Survey

    OpenAIRE

    Kolios, Stavros; Maurodimou, Olga; Stylios, Chrysostomos

    2013-01-01

    Part 6: Performance Management; International audience; The installation and operation of instrument/sensor networks has great importance in monitoring the physical environment from local to global scale. Nowadays, such networks comprise vital parts of integrated information systems that are called Environmental Information Systems (EIS). Such systems provide real time monitoring, forecasts and interesting conclusions extracted from the collected data sets that are stored in huge databases. T...

  14. Integrated Short Range, Low Bandwidth, Wearable Communications Networking Technologies

    Science.gov (United States)

    2012-04-30

    savings of 30mA of 7.2V battery current in the MSP430 audio circuit was harvested by activating a DAC on the MSP430 code. The Blackfin serial...investigative work, testing and collaboration with digital-to-analog ( DAC ) experts at Analog Devices, resolution to a distortion issue was achieved...This issue was resolved by adding small capacitors between the input pin of the DAC and ground. This modification restored the signal integrity of

  15. Short (

    NARCIS (Netherlands)

    Telleman, Gerdien; den Hartog, Laurens

    2013-01-01

    Aim: This systematic review assessed the implant survival rate of short (<10 mm) dental implants installed in partially edentulous patients. A case report of a short implant in the posterior region have been added. Materials and methods: A search was conducted in the electronic databases of MEDLINE

  16. Integrated Filters for Short Range Wireless and Biomedical Applications

    CERN Document Server

    Laoudias, Costas

    2012-01-01

    This book describes the design of low-voltage analog integrated filters using current mirrors, one of the most common building blocks both in analog and mixed-signal VLSI circuits, offering the advantages of low-voltage operation, derivation of resistorless topologies and electronic adjustment capability of their frequency characteristics.  Several design examples are described, using current mirrors that fulfill the requirements of modern low-power wireless and biomedical applications, such as universal biquadratic filter topologies, complex filters for Bluetooth/ZigBee low-IF receivers and Wavelet filters for cardiac signal detection. The experimental results from the fabricated chips will also be presented, showing their utility in modern low-voltage low-power portable devices.

  17. Lie Algebraic Structures and Integrability of Long-Short Wave Equation in (2+1) Dimensions

    Institute of Scientific and Technical Information of China (English)

    ZHAO Xue-Qing; L(U)Jing-Fa

    2004-01-01

    The hidden symmetry and integrability of the long-short wave equation in (2+1) dimensions are considered using the prolongation approach. The internal algebraic structures and their linear spectra are derived in detail which show that the equation is integrable.

  18. Short-term outcomes of the prospective multicentre 'Prostate Cancer Research International : Active Surveillance' study

    NARCIS (Netherlands)

    van den Bergh, Roderick C. N.; Vasarainen, Hanna; van der Poel, Henk G.; Vis-Maters, Jenneke J.; Rietbergen, John B.; Pickles, Tom; Cornel, Erik B.; Valdagni, Riccardo; Jaspars, Joris J.; van der Hoeven, John; Staerman, Frederic; Oomens, Eric H. G. M.; Rannikko, Antti; Roemeling, Stijn; Steyerberg, Ewout W.; Roobol, Monique J.; Schroder, Fritz H.; Bangma, Chris H.

    2010-01-01

    OBJECTIVE To evaluate the short-term outcomes of the prospective international Prostate Cancer Research International: Active Surveillance ('PRIAS') study (Dutch Trial Register NTR1718), as active surveillance (AS) for early prostate cancer might provide a partial solution to the current overtreatme

  19. Clotrimazole as a Cancer Drug: A Short Review

    OpenAIRE

    S, Kadavakollu; C, Stailey; CS, Kunapareddy; S, White

    2014-01-01

    Although clotrimazole was first used against fungal infections, a body of research was later developed indicating that this drug has anticancer properties as well. The mechanism of action is based on the inhibition of mitochondrial-bound glycolytic enzymes and calmodulin, which starves cancer cells of energy. Clotrimazole and its derivatives have been shown to decrease rates of cancer cell proliferation, induce G1 phase arrest, and promote pro-apoptotic factors, which lead to cell death.

  20. Integration of genomics in cancer care

    DEFF Research Database (Denmark)

    Santos, Erika Maria Monteiro; Edwards, Quannetta T; Floria-Santos, Milena

    2013-01-01

    cancer syndromes, epigenetics factors, and management of care considerations. METHODS: Peer-reviewed literature and expert professional guidelines were reviewed to address concepts of genetics-genomics in cancer care. FINDINGS: Cancer is now known to be heterogeneous at the molecular level, with genetic...

  1. Integration of prostate cancer clinical data using an ontology.

    Science.gov (United States)

    Min, Hua; Manion, Frank J; Goralczyk, Elizabeth; Wong, Yu-Ning; Ross, Eric; Beck, J Robert

    2009-12-01

    It is increasingly important for investigators to efficiently and effectively access, interpret, and analyze the data from diverse biological, literature, and annotation sources in a unified way. The heterogeneity of biomedical data and the lack of metadata are the primary sources of the difficulty for integration, presenting major challenges to effective search and retrieval of the information. As a proof of concept, the Prostate Cancer Ontology (PCO) is created for the development of the Prostate Cancer Information System (PCIS). PCIS is applied to demonstrate how the ontology is utilized to solve the semantic heterogeneity problem from the integration of two prostate cancer related database systems at the Fox Chase Cancer Center. As the results of the integration process, the semantic query language SPARQL is applied to perform the integrated queries across the two database systems based on PCO.

  2. Work-up times in an integrated brain cancer pathway

    DEFF Research Database (Denmark)

    Lund Laursen, Emilie; Rasmussen, Birthe Krogh

    2012-01-01

    The integrated brain cancer pathway (IBCP) aims to ensure fast-track diagnostics and treatment for brain cancers in Denmark. This paper focuses on the referral pattern and the time frame of key pathway elements during the first two years following implementation of the IBCP in a regional neurology...

  3. The mathematics of cancer: integrating quantitative models.

    Science.gov (United States)

    Altrock, Philipp M; Liu, Lin L; Michor, Franziska

    2015-12-01

    Mathematical modelling approaches have become increasingly abundant in cancer research. The complexity of cancer is well suited to quantitative approaches as it provides challenges and opportunities for new developments. In turn, mathematical modelling contributes to cancer research by helping to elucidate mechanisms and by providing quantitative predictions that can be validated. The recent expansion of quantitative models addresses many questions regarding tumour initiation, progression and metastases as well as intra-tumour heterogeneity, treatment responses and resistance. Mathematical models can complement experimental and clinical studies, but also challenge current paradigms, redefine our understanding of mechanisms driving tumorigenesis and shape future research in cancer biology.

  4. Semiquantitative diagnosis of cancer using short-lived radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Tomio; Oriuchi, Noboru; Endo, Keigo [Gunma Univ., Maebashi (Japan). School of Medicine

    1997-03-01

    The accuracy and usefulness of semiquantitative diagnoses of SPECT using radiolabeled monoclonal antibodies in patients with colorectal cancer and PET using FDG in patients with recurrent lung cancer were investigated. The tumor to normal tissue count ratio (T/N ratio) was determined with SPECT and compared with the same index (T/N ratio) obtained by measuring radioactivity in tumor and normal tissue of the resected specimens. Significant correlation between SPECT T/N ratios and tissue T/N ratio was observed (r=0.92, p<0.001, n=8). In PET study, standardized uptake value (SUV) was obtained with PET images and assessed the difference in SUV between recurrent tumors and noncancerous lesions. The relationship between the SUV threshold and diagnostic accuracy in differentiating recurrent tumors from post-treatment changes was also assessed. The maximum SUV in recurrent tumor ranged from 3.0 to 25.8 with a mean {+-} s.d. of 11.2 {+-} 5.7 (n=16) and in the noncancerous lesion ranged from 2.0 to 7.5 with a mean {+-} s.d. of 3.5 {+-} 1.8 (n=9). The SUV was significantly higher in the recurrent cancer (P<0.0001). A threshold SUV of 5.0 provided optimal diagnostic accuracy (sensitivity 93.8%, specificity 88.9%, accuracy 92.0%). It was superior to visual interpretation of FDG PET (sensitivity 100%, specificity 55.6%, accuracy 84%). In conclusion, semiquantitative diagnoses with SPECT using radiolabeled monoclonal antibody and PET using FDG were accurate and useful in detecting malignant tumors. (author)

  5. Introducing a short measure of shared servant leadership impacting team performance through team behavioral integration

    NARCIS (Netherlands)

    M. Sousa (Milton); D. van Dierendonck (Dirk)

    2016-01-01

    textabstractThe research reported in this paper was designed to study the influence of shared servant leadership on team performance through the mediating effect of team behavioral integration, while validating a new short measure of shared servant leadership. A round-robin approach was used to coll

  6. The effect of a short integrated study skills programme for first-year

    NARCIS (Netherlands)

    Stegers-Jager, K.M.; Cohen-Schotanus, J.; Themmen, A.P.

    2012-01-01

    Background: There is a need for outcome-based studies on strategies for supporting at-risk medical students that use long-term follow-up and contemporaneous controls. AIM: To measure the effect of a short integrated study skills programme (SSP) on the study progress of at-risk medical students. METH

  7. Integration of proteomics into systems biology of cancer.

    Science.gov (United States)

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

    2012-01-01

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

  8. Short-term effects of night shift work on breast cancer risk

    DEFF Research Database (Denmark)

    Vistisen, Helene Tilma; Garde, Anne Helene; Frydenberg, Morten;

    2016-01-01

    Objectives The objective was to examine if night shift work is a short-term risk factor for breast cancer, including combined estrogen receptor (ER) and human epidermal growth factor 2 (HER2) breast cancer subtypes. Methods The cohort comprised 155 540 public sector female workers in Denmark who...... were followed from 2007-2012. Day-to-day work-hour information was available from payroll registers and 1245 incident cases of breast cancer were identified in national cancer registries together with receptor subtype information. Results A rate ratio (RR) of 0.90 [95% confidence interval (95% CI) 0.......80-1.01] was observed for workers ever working night shifts during the follow-up period compared with workers only working day shifts after adjustment for age, age at first child, parity, family history of breast or ovarian cancer, sex hormones, medications related to alcoholism, family educational level, mammography...

  9. Discovering cancer genes by integrating network and functional properties

    Directory of Open Access Journals (Sweden)

    Davis David P

    2009-09-01

    Full Text Available Abstract Background Identification of novel cancer-causing genes is one of the main goals in cancer research. The rapid accumulation of genome-wide protein-protein interaction (PPI data in humans has provided a new basis for studying the topological features of cancer genes in cellular networks. It is important to integrate multiple genomic data sources, including PPI networks, protein domains and Gene Ontology (GO annotations, to facilitate the identification of cancer genes. Methods Topological features of the PPI network, as well as protein domain compositions, enrichment of gene ontology categories, sequence and evolutionary conservation features were extracted and compared between cancer genes and other genes. The predictive power of various classifiers for identification of cancer genes was evaluated by cross validation. Experimental validation of a subset of the prediction results was conducted using siRNA knockdown and viability assays in human colon cancer cell line DLD-1. Results Cross validation demonstrated advantageous performance of classifiers based on support vector machines (SVMs with the inclusion of the topological features from the PPI network, protein domain compositions and GO annotations. We then applied the trained SVM classifier to human genes to prioritize putative cancer genes. siRNA knock-down of several SVM predicted cancer genes displayed greatly reduced cell viability in human colon cancer cell line DLD-1. Conclusion Topological features of PPI networks, protein domain compositions and GO annotations are good predictors of cancer genes. The SVM classifier integrates multiple features and as such is useful for prioritizing candidate cancer genes for experimental validations.

  10. A multilevel data integration resource for breast cancer study

    Directory of Open Access Journals (Sweden)

    Viti Federica

    2010-06-01

    Full Text Available Abstract Background Breast cancer is one of the most common cancer types. Due to the complexity of this disease, it is important to face its study with an integrated and multilevel approach, from genes, transcripts and proteins to molecular networks, cell populations and tissues. According to the systems biology perspective, the biological functions arise from complex networks: in this context, concepts like molecular pathways, protein-protein interactions (PPIs, mathematical models and ontologies play an important role for dissecting such complexity. Results In this work we present the Genes-to-Systems Breast Cancer (G2SBC Database, a resource which integrates data about genes, transcripts and proteins reported in literature as altered in breast cancer cells. Beside the data integration, we provide an ontology based query system and analysis tools related to intracellular pathways, PPIs, protein structure and systems modelling, in order to facilitate the study of breast cancer using a multilevel perspective. The resource is available at the URL http://www.itb.cnr.it/breastcancer. Conclusions The G2SBC Database represents a systems biology oriented data integration approach devoted to breast cancer. By means of the analysis capabilities provided by the web interface, it is possible to overcome the limits of reductionist resources, enabling predictions that can lead to new experiments.

  11. Effectiveness of the Mindfulness Art Therapy Short Version for Japanese Patients with Advanced Cancer

    Science.gov (United States)

    Ando, Michiyo; Kira, Haruko; Hayashida, Shigeru; Ito, Sayoko

    2016-01-01

    The aim of this study was to investigate the feasibility of the Mindfulness Art Therapy Short Version for Japanese patients with advanced cancer. Patients learned mindfulness practices and then made art to express their feelings in the first session. After receiving instruction on practicing mindfulness 2 weeks later, they participated in a second…

  12. Nanoshell bioconjugates for integrated imaging and therapy of cancer

    Science.gov (United States)

    Loo, Christopher H.; Lee, Min-Ho; Hirsch, Leon R.; West, Jennifer L.; Halas, Naomi J.; Drezek, Rebekah A.

    2004-06-01

    Currently, separate diagnostic and therapeutic modalities are required for the diagnosis and treatment of cancer. In many cases, the present standard of care requires invasive surgical procedures and/or other treatments associated with significant side effect profiles, high cost, and poor clinical outcome. A single technology with dual diagnostic/therapeutic capabilities would potentially yield significant savings in the time and cost associated with diagnosing and treating many cancers. In this paper, we discuss gold nanoshell bioconjugates and their role in the development of an integrated cancer imaging and therapy application. Nanoshells are a novel class of nanomaterials that have unique properties including continuous and broad wavelength tunability, far greater scattering and absorption coefficients, increased chemical stability, and improved biocompatibility. Here, we describe the development of an integrated cancer imaging and therapy application using near-infrared (NIR) gold nanoshell bioconjugates.

  13. Integrative Nanomedicine: Treating Cancer With Nanoscale Natural Products

    OpenAIRE

    Bell, Iris R.; Sarter, Barbara; Koithan, Mary; Banerji, Prasanta; Banerji, Pratip; Jain, Shamini; Ives, John

    2014-01-01

    Finding safer and more effective treatments for specific cancers remains a significant challenge for integrative clinicians and researchers worldwide. One emerging strategy is the use of nanostructured forms of drugs, vaccines, traditional animal venoms, herbs, and nutraceutical agents in cancer treatment. The recent discovery of nanoparticles in traditional homeopathic medicines adds another point of convergence between modern nanomedicine and alternative interventional strategies. A way in ...

  14. Modulators of prostate cancer cell proliferation and viability identified by short-hairpin RNA library screening.

    Directory of Open Access Journals (Sweden)

    Kimberly Brown Dahlman

    Full Text Available There is significant need to identify novel prostate cancer drug targets because current hormone therapies eventually fail, leading to a drug-resistant and fatal disease termed castration-resistant prostate cancer. To functionally identify genes that, when silenced, decrease prostate cancer cell proliferation or induce cell death in combination with antiandrogens, we employed an RNA interference-based short hairpin RNA barcode screen in LNCaP human prostate cancer cells. We identified and validated four candidate genes (AKT1, PSMC1, STRADA, and TTK that impaired growth when silenced in androgen receptor positive prostate cancer cells and enhanced the antiproliferative effects of antiandrogens. Inhibition of AKT with a pharmacologic inhibitor also induced apoptosis when combined with antiandrogens, consistent with recent evidence for PI3K and AR pathway crosstalk in prostate cancer cells. Recovery of hairpins targeting a known prostate cancer pathway validates the utility of shRNA library screening in prostate cancer as a broad strategy to identify new candidate drug targets.

  15. Modulators of prostate cancer cell proliferation and viability identified by short-hairpin RNA library screening.

    Science.gov (United States)

    Dahlman, Kimberly Brown; Parker, Joel S; Shamu, Tambudzai; Hieronymus, Haley; Chapinski, Caren; Carver, Brett; Chang, Kenneth; Hannon, Gregory J; Sawyers, Charles L

    2012-01-01

    There is significant need to identify novel prostate cancer drug targets because current hormone therapies eventually fail, leading to a drug-resistant and fatal disease termed castration-resistant prostate cancer. To functionally identify genes that, when silenced, decrease prostate cancer cell proliferation or induce cell death in combination with antiandrogens, we employed an RNA interference-based short hairpin RNA barcode screen in LNCaP human prostate cancer cells. We identified and validated four candidate genes (AKT1, PSMC1, STRADA, and TTK) that impaired growth when silenced in androgen receptor positive prostate cancer cells and enhanced the antiproliferative effects of antiandrogens. Inhibition of AKT with a pharmacologic inhibitor also induced apoptosis when combined with antiandrogens, consistent with recent evidence for PI3K and AR pathway crosstalk in prostate cancer cells. Recovery of hairpins targeting a known prostate cancer pathway validates the utility of shRNA library screening in prostate cancer as a broad strategy to identify new candidate drug targets.

  16. Short term integrative meditation improves resting alpha activity and stroop performance.

    Science.gov (United States)

    Fan, Yaxin; Tang, Yi-Yuan; Tang, Rongxiang; Posner, Michael I

    2014-12-01

    Our previous research showed that short term meditation training reduces the time to resolve conflict in the flanker task. Studies also show that resting alpha increases with long term meditation practice. The aim of this study is to determine whether short term meditation training both increases resting alpha activity and reduces the time to resolve conflict in the Stroop task and whether these two effects are related. Forty-three Chinese undergraduates were randomly assigned an experiment group given 5 days meditation training using integrative body-mind training (IBMT) and a relaxation training control. After training, only the IBMT group showed decreased conflict reaction time (RT), and increased resting mean alpha power. Moreover, the higher the enhancement of resting alpha power, the stronger the improvement of conflict RT. The results indicate that short term meditation diffusely enhances alpha and improves the ability to deal with conflict and moreover these two effects are positively related.

  17. Introducing a Short Measure of Shared Servant Leadership Impacting Team Performance through Team Behavioral Integration

    OpenAIRE

    Milton eSousa; Dirk evan Dierendonck

    2016-01-01

    The research reported in this paper was designed to study the influence of shared servant leadership on team performance through the mediating effect of team behavioural integration, while validating a new short measure of shared servant leadership. A round-robin approach was used to collect data in two similar studies. Study 1 included 244 undergraduate students in 61 teams following an intense HRM business simulation of two weeks. The following year, study 2 included 288 students in 72 team...

  18. Integrated Power Flow and Short Circuit Calculation Method for Distribution Network with Inverter Based Distributed Generation

    Directory of Open Access Journals (Sweden)

    Shan Yang

    2016-01-01

    Full Text Available Power flow calculation and short circuit calculation are the basis of theoretical research for distribution network with inverter based distributed generation. The similarity of equivalent model for inverter based distributed generation during normal and fault conditions of distribution network and the differences between power flow and short circuit calculation are analyzed in this paper. Then an integrated power flow and short circuit calculation method for distribution network with inverter based distributed generation is proposed. The proposed method let the inverter based distributed generation be equivalent to Iθ bus, which makes it suitable to calculate the power flow of distribution network with a current limited inverter based distributed generation. And the low voltage ride through capability of inverter based distributed generation can be considered as well in this paper. Finally, some tests of power flow and short circuit current calculation are performed on a 33-bus distribution network. The calculated results from the proposed method in this paper are contrasted with those by the traditional method and the simulation method, whose results have verified the effectiveness of the integrated method suggested in this paper.

  19. Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer.

    Science.gov (United States)

    Zhang, Hui; Liu, Tao; Zhang, Zhen; Payne, Samuel H; Zhang, Bai; McDermott, Jason E; Zhou, Jian-Ying; Petyuk, Vladislav A; Chen, Li; Ray, Debjit; Sun, Shisheng; Yang, Feng; Chen, Lijun; Wang, Jing; Shah, Punit; Cha, Seong Won; Aiyetan, Paul; Woo, Sunghee; Tian, Yuan; Gritsenko, Marina A; Clauss, Therese R; Choi, Caitlin; Monroe, Matthew E; Thomas, Stefani; Nie, Song; Wu, Chaochao; Moore, Ronald J; Yu, Kun-Hsing; Tabb, David L; Fenyö, David; Bafna, Vineet; Wang, Yue; Rodriguez, Henry; Boja, Emily S; Hiltke, Tara; Rivers, Robert C; Sokoll, Lori; Zhu, Heng; Shih, Ie-Ming; Cope, Leslie; Pandey, Akhilesh; Zhang, Bing; Snyder, Michael P; Levine, Douglas A; Smith, Richard D; Chan, Daniel W; Rodland, Karin D

    2016-07-28

    To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass-spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSCs). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease, such as how different copy-number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, and the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC. VIDEO ABSTRACT.

  20. A short latency between radiation exposure from nuclear plants and cancer in young children.

    Science.gov (United States)

    Mangano, Joseph J

    2006-01-01

    Previous reports document a short latency of cancer onset in young children exposed to low doses of radioactivity. The standard mortality ratio (SMR) for cancer in children dying before age ten rose in the period 6-10 years after the Three Mile Island and Chernobyl accidents in populations most exposed to fallout. SMRs near most nuclear power plants were elevated 6-10 years after startup, particularly for leukemia. Cancer incidence in children under age ten living near New York and New Jersey nuclear plants increased 4-5 years after increases in average strontium-90 in baby teeth, and declined 4-5 years after Sr-90 averages dropped. The assumption that Sr-90 and childhood cancer are correlated is best supported for a supralinear dose-response, meaning the greatest per-dose risks are at the lowest doses. Findings document that the very young are especially susceptible to adverse effects of radiation exposure, even at relatively low doses.

  1. Integrating Heterogeneous Biomedical Data for Cancer Research: the CARPEM infrastructure

    OpenAIRE

    2016-01-01

    Summary Cancer research involves numerous disciplines. The multiplicity of data sources and their heterogeneous nature render the integration and the exploration of the data more and more complex. Translational research platforms are a promising way to assist scientists in these tasks. In this article, we identify a set of scientific and technical principles needed to build a translational research platform compatible with ethical requirements, data protection and data-integration problems. W...

  2. Status of integrated irradiation and cystectomy for bladder cancer.

    Science.gov (United States)

    Whitmore, W F; Batata, M

    1984-11-01

    The rationale and representative results of integrated irradiation and cystectomy for bladder cancer are reviewed and an hypothesis regarding the mechanism and benefits of such treatment formulated. The basis for uncertainty regarding the value of preoperative irradiation is outlined and a perspective on the resolution of this uncertainty provided.

  3. Ozone depletion and skin cancer incidence: an integrated modelling approach

    NARCIS (Netherlands)

    Slaper H; den Elzen MGJ; de Woerd HJ; de Greef J

    1992-01-01

    A decrease in stratospheric ozone, probably caused by chlorofluorocarbon (CFC) emissions, has been observed over large parts of the globe. The incidence of skin cancer is expected to increase due to ozone depletion. An integrated source-risk model is developed and applied to evaluate the increased

  4. Gene transcriptional networks integrate microenvironmental signals in human breast cancer.

    Science.gov (United States)

    Xu, Ren; Mao, Jian-Hua

    2011-04-01

    A significant amount of evidence shows that microenvironmental signals generated from extracellular matrix (ECM) molecules, soluble factors, and cell-cell adhesion complexes cooperate at the extra- and intracellular level. This synergetic action of microenvironmental cues is crucial for normal mammary gland development and breast malignancy. To explore how the microenvironmental genes coordinate in human breast cancer at the genome level, we have performed gene co-expression network analysis in three independent microarray datasets and identified two microenvironment networks in human breast cancer tissues. Network I represents crosstalk and cooperation of ECM microenvironment and soluble factors during breast malignancy. The correlated expression of cytokines, chemokines, and cell adhesion proteins in Network II implicates the coordinated action of these molecules in modulating the immune response in breast cancer tissues. These results suggest that microenvironmental cues are integrated with gene transcriptional networks to promote breast cancer development.

  5. Linking Genetic Counseling Content to Short-Term Outcomes in Individuals at Elevated Breast Cancer Risk

    Science.gov (United States)

    Ellington, Lee; Schoenberg, Nancy; Agarwal, Parul; Jackson, Thomas; Dickinson, Stephanie; Abraham, Jame; Paskett, Electra D.; Leventhal, Howard; Andrykowski, Michael

    2014-01-01

    Few studies have linked actual genetic counseling content to short-term outcomes. Using the Self-regulation Model, the impact of cognitive and affective content in genetic counseling on short-term outcomes was studied in individuals at elevated risk of familial breast-ovarian cancer. Surveys assessed dependent variables: distress, perceived risk, and 6 knowledge measures (Meaning of Positive Test; Meaning of Negative Test; Personal Behavior; Practitioner Knowledge; Mechanisms of Cancer Inheritance; Frequency of Inherited Cancer) measured at pre- and post-counseling. Proportion of participant cognitive and affective and counselor cognitive and affective content during sessions (using LIWC software) were predictors in regressions. Knowledge increased for 5 measures and decreased for Personal Behavior, Distress and Perceived Risk. Controlling for age and education, results were significant/marginally significant for three measures. More counselor content was associated with decreases in knowledge of Personal Behavior. More participant and less counselor affective content was associated with gains in Practitioner Knowledge. More counselor cognitive, and interaction of counselor cognitive and affective content, were associated with higher perceived risk. Genetic counselors dominate the content of counseling sessions. Therefore, their content is tied more closely to short term outcomes than participant content. A lack of patient communication in sessions may pose problems for understanding of complex concepts. PMID:24671341

  6. Short, sharp shock public health campaign had limited impact on raising awareness of laryngeal cancer.

    Science.gov (United States)

    Sethi, Neeraj; Rafferty, Amy; Rawnsley, Trisha; Jose, Jemy

    2016-09-01

    Laryngeal cancer has poorer outcomes if diagnosed at a later stage. Improving awareness could encourage earlier presentation and improve outcomes. This study aimed to evaluate a public engagement campaign targeted at raising awareness of laryngeal cancer. An epidemiological study identified high-risk populations in the region. A target population as well as a matched control population was selected. A cancer awareness survey combined with focus groups guided the design of a 3-month multimedia campaign. The survey was repeated post-campaign to evaluate the campaign effectiveness. The study identified populations with the highest rates of laryngeal cancer and late stage disease at presentation. The surveys performed revealed a limited effect of the multimedia campaign in raising awareness of the signs and symptoms of laryngeal cancer. Recall of the campaign also faded rapidly. This is the first public awareness campaign aimed at laryngeal cancer carried out in the UK. The results suggest that short-term campaigns have a limited effect and a more prolonged approach should be considered.

  7. Short-course hypofrationated radiochemotherapy for unresectable locally advanced cancer of the base of tongue: Palliation only? A case report and short review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Kalogeridi, Maria-Aggeliki; Zygogianni, Anna; Kyrgias, George [University Hospital of Larissa, Larissa (Greece); Kouloulias, Vassilios [School of Health Sciences, Kapodistrian University of Athens, Athens (Greece)

    2014-06-15

    We present a case of unresectable cancer of the base of tongue treated with hypofractionated 3D conformal radiotherapy and concomitant chemotherapy. Based on the excellent tumour response in this radiotherapy regimen and international experience in short course treatments we shortly reviewed, we propose that this therapeutic approach could be considered in a curative setting for patients unsuitable for the a standard long course radiochemotherapy schedule.

  8. Integration of real options into short-term mine planning and production scheduling

    Institute of Scientific and Technical Information of China (English)

    LI Shu-xing; KNIGHTS Peter

    2009-01-01

    Commodity prices have fallen sharply due to the global financial crisis. This has adversely affected the viability of some mining projects, including leading to the possibility of bankruptcy for some companies. These price falls reflect uncertainties and risks associated with mining projects. In recent years, much work has been published related to the application of real options pric-ing theory to value life-of-mine plans in response to long term financial uncertainty and risk. However, there are uncertainties and risks associated with medium/short-term mining operations. Real options theory can also be applied to tactical decisions involving uncertainties and risks. This paper will investigate the application of real options in the mining industry and present a methodology developed at University of Queensland, Australia, for integrating real options into medium/short-term mine planning and produc-tion scheduling. A case study will demonstrate the validity and usefulness of the methodology and techniques developed.

  9. Short-Term Prognostic Index for Breast Cancer: NPI or Lpi

    Directory of Open Access Journals (Sweden)

    V. Van Belle

    2011-01-01

    Full Text Available Axillary lymph node involvement is an important prognostic factor for breast cancer survival but is confounded by the number of nodes examined. We compare the performance of the log odds prognostic index (Lpi, using a ratio of the positive versus negative lymph nodes, with the Nottingham Prognostic Index (NPI for short-term breast cancer specific disease free survival. A total of 1818 operable breast cancer patients treated in the University Hospital of Leuven between 2000 and 2005 were included. The performance of the NPI and Lpi were compared on two levels: calibration and discrimination. The latter was evaluated using the concordance index (cindex, the number of patients in the extreme groups, and difference in event rates between these. The NPI had a significant higher cindex, but a significant lower percentage of patients in the extreme risk groups. After updating both indices, no significant differences between NPI and Lpi were noted.

  10. Psychiatric benefits of integrative therapies in patients with cancer.

    Science.gov (United States)

    Cassileth, Barrie R

    2014-02-01

    Integrative oncology uses non-pharmacological adjuncts to mainstream care to manage physical, emotional, and psychological symptoms experienced by cancer survivors. Depression, anxiety, fatigue and pain are among the common, often burdensome symptoms that can occur in clusters, deplete patient morale, interfere with treatment plans, and hamper recovery. Patients already seek various modalities on their own to address a broad range of problems. Legitimate complementary therapies offered at major cancer institutions improve quality of life, speed recovery, and optimize patient support. They also augment the benefits of psychiatric interventions, due to their ability to increase self-awareness and improve physical and psychological conditioning. Further, these integrated therapies provide lifelong tools and develop skills that patients use well after treatment to develop self-care regimens. The active referral of patients to integrative therapies achieves three important objectives: complementary care is received from therapists experienced in working with cancer patients, visits become part of the medical record, allowing treatment teams to guide individuals in maximizing benefit, and patients are diverted from useless or harmful 'alternatives.' We review the reciprocal physical and psychiatric benefits of exercise, mind-body practices, massage, acupuncture, and music therapy for cancer survivors, and suggest how their use can augment mainstream psychiatric interventions.

  11. Use of comparative data for integrated cancer services

    Directory of Open Access Journals (Sweden)

    McCarthy Mark

    2007-12-01

    Full Text Available Abstract Background Comparative data are an important resource for management of integrated care. In 2001, the English Department of Health created 34 cancer networks, broadly serving populations of half to three million people, to coordinate cancer services across providers. We have investigated how national and regional routine data are used by the cancer network management teams. Methods Telephone interviews using a standardised semi-structured questionnaire were conducted with 68 participants in 29 cancer network teams. Replies were analysed both quantitatively and qualitatively. Results While most network teams had a formal information strategy, data were used ad hoc more than regularly, and were not thought to be as influential in network decision making as other sources of information. Data collection was more prominent in information strategies than data use. Perceptions of data usefulness were mixed and there were worries over data quality, relevance, and potential misuse. Participants were receptive to the idea of a new limited dataset collating comparative data from currently available routine data sources. Few network structural factors were associated with data use, perceptions of current data, or receptivity to a new dataset. Conclusion Comparative data are underused for managing integrated cancer services in England. Managers would welcome more comparative data, but also desired data to be relevant, quality assured and contextualised, and for the teams to be better resourced for data use.

  12. Tightly coupled long baseline/ultra-short baseline integrated navigation system

    Science.gov (United States)

    Batista, Pedro; Silvestre, Carlos; Oliveira, Paulo

    2016-06-01

    This paper proposes a novel integrated navigation filter based on a combined long baseline/ultra short baseline acoustic positioning system with application to underwater vehicles. With a tightly coupled structure, the position, linear velocity, attitude, and rate gyro bias are estimated, considering the full nonlinear system dynamics without resorting to any algebraic inversion or linearisation techniques. The resulting solution ensures convergence of the estimation error to zero for all initial conditions, exponentially fast. Finally, it is shown, under simulation environment, that the filter achieves very good performance in the presence of sensor noise.

  13. Integrating cannabis into clinical cancer care.

    Science.gov (United States)

    Abrams, D I

    2016-03-01

    Cannabis species have been used as medicine for thousands of years; only since the 1940s has the plant not been widely available for medical use. However, an increasing number of jurisdictions are making it possible for patients to obtain the botanical for medicinal use. For the cancer patient, cannabis has a number of potential benefits, especially in the management of symptoms. Cannabis is useful in combatting anorexia, chemotherapy-induced nausea and vomiting, pain, insomnia, and depression. Cannabis might be less potent than other available antiemetics, but for some patients, it is the only agent that works, and it is the only antiemetic that also increases appetite. Inhaled cannabis is more effective than placebo in ameliorating peripheral neuropathy in a number of conditions, and it could prove useful in chemotherapy-induced neuropathy. A pharmacokinetic interaction study of vaporized cannabis in patients with chronic pain on stable doses of sustained-release opioids demonstrated no clinically significant change in plasma opiates, while suggesting the possibility of synergistic analgesia. Aside from symptom management, an increasing body of in vitro and animal-model studies supports a possible direct anticancer effect of cannabinoids by way of a number of different mechanisms involving apoptosis, angiogenesis, and inhibition of metastasis. Despite an absence of clinical trials, abundant anecdotal reports that describe patients having remarkable responses to cannabis as an anticancer agent, especially when taken as a high-potency orally ingested concentrate, are circulating. Human studies should be conducted to address critical questions related to the foregoing effects.

  14. Introducing a short measure of shared servant leadership impacting team performance through team behavioral integration

    Directory of Open Access Journals (Sweden)

    Milton eSousa

    2016-01-01

    Full Text Available The research reported in this paper was designed to study the influence of shared servant leadership on team performance through the mediating effect of team behavioural integration, while validating a new short measure of shared servant leadership. A round-robin approach was used to collect data in two similar studies. Study 1 included 244 undergraduate students in 61 teams following an intense HRM business simulation of two weeks. The following year, study 2 included 288 students in 72 teams involved in the same simulation. The most important findings were that (1 shared servant leadership was a strong determinant of team behavioural integration, (2 information exchange worked as the main mediating process between shared servant leadership and team performance, and (3 the essence of servant leadership can be captured on the key dimensions of empowerment, humility, stewardship and accountability, allowing for a new promising shortened four-dimensional measure of shared servant leadership.

  15. Introducing a Short Measure of Shared Servant Leadership Impacting Team Performance through Team Behavioral Integration.

    Science.gov (United States)

    Sousa, Milton; Van Dierendonck, Dirk

    2015-01-01

    The research reported in this paper was designed to study the influence of shared servant leadership on team performance through the mediating effect of team behavioral integration, while validating a new short measure of shared servant leadership. A round-robin approach was used to collect data in two similar studies. Study 1 included 244 undergraduate students in 61 teams following an intense HRM business simulation of 2 weeks. The following year, study 2 included 288 students in 72 teams involved in the same simulation. The most important findings were that (1) shared servant leadership was a strong determinant of team behavioral integration, (2) information exchange worked as the main mediating process between shared servant leadership and team performance, and (3) the essence of servant leadership can be captured on the key dimensions of empowerment, humility, stewardship and accountability, allowing for a new promising shortened four-dimensional measure of shared servant leadership.

  16. THE INTEGRATED SHORT-TERM STATISTICAL SURVEYS: EXPERIENCE OF NBS IN MOLDOVA

    Directory of Open Access Journals (Sweden)

    Oleg CARA

    2012-07-01

    Full Text Available The users’ rising need for relevant, reliable, coherent, timely data for the early diagnosis of the economic vulnerability and of the turning points in the business cycles, especially during a financial and economic crisis, asks for a prompt answer, coordinated by statistical institutions. High quality short term statistics are of special interest for the emerging market economies, such as the Moldavian one, being extremely vulnerable when facing economic recession. Answering to the challenges of producing a coherent and adequate image of the economic activity, by using the system of indicators and definitions efficiently applied at the level of the European Union, the National Bureau of Statistics (NBS of the Republic of Moldova has launched the development process of an integrated system of short term statistics (STS based on the advanced international experience.Thus, in 2011, BNS implemented the integrated statistical survey on STS based on consistent concepts, harmonized with the EU standards. The integration of the production processes, which were previously separated, is based on a common technical infrastructure, standardized procedures and techniques for data production. The achievement of this complex survey with holistic approach has allowed the consolidation of the statistical data quality, comparable at European level and the signifi cant reduction of information burden on business units, especially of small size.The reformation of STS based on the integrated survey has been possible thanks to the consistent methodological and practical support given to NBS by the National Institute of Statistics (INS of Romania, for which we would like to thank to our Romanian colleagues.

  17. Evaluation of Tumor Response after Short-Course Radiotherapy and Delayed Surgery for Rectal Cancer

    Science.gov (United States)

    Rega, Daniela; Pecori, Biagio; Scala, Dario; Avallone, Antonio; Pace, Ugo; Petrillo, Antonella; Aloj, Luigi; Tatangelo, Fabiana; Delrio, Paolo

    2016-01-01

    Purpose Neoadjuvant therapy is able to reduce local recurrence in rectal cancer. Immediate surgery after short course radiotherapy allows only for minimal downstaging. We investigated the effect of delayed surgery after short-course radiotherapy at different time intervals before surgery, in patients affected by rectal cancer. Methods From January 2003 to December 2013 sixty-seven patients with the following characteristics have been selected: clinical (c) stage T3N0 ≤ 12 cm from the anal verge and with circumferential resection margin > 5 mm (by magnetic resonance imaging); cT2, any N, CRM+ve who resulted unfit for chemo-radiation, were also included. Patients underwent preoperative short-course radiotherapy with different interval to surgery were divided in three groups: A (within 6 weeks), B (between 6 and 8 weeks) and C (after more than 8 weeks). Hystopatolgical response to radiotherapy was measured by Mandard’s modified tumor regression grade (TRG). Results All patients completed the scheduled treatment. Sixty-six patients underwent surgery. Fifty-three of which (80.3%) received a sphincter saving procedure. Downstaging occurred in 41 cases (62.1%). The analysis of subgroups showed an increasing prevalence of TRG 1–2 prolonging the interval to surgery (group A—16.7%, group B—36.8% and 54.3% in group C; p value 0.023). Conclusions Preoperative short-course radiotherapy is able to downstage rectal cancer if surgery is delayed. A higher rate of TRG 1–2 can be obtained if interval to surgery is prolonged to more than 8 weeks. PMID:27548058

  18. Probing the Nature of Short Swift Bursts via Deep INTEGRAL Monitoring of GRB 050925

    Science.gov (United States)

    Sakamoto, T.; Barbier, L.; Barthelmy, S. D.; Cummings, J. R.; Fenimore, E. E.; Gehrels, N.; Krimm, H. A.; Markwardt, C. B.; Palmer, D. M.; Parsons, A. M.; Sato, G.; Stamatikos, M.; Tueller, J.

    2010-01-01

    We present results from Swift, XMM-Newton, and deep INTEGRAL monitoring in the region of GRB 050925. This short Swift burst is a candidate for a newly discovered soft gamma-ray repeater (SGR) with the following observational burst properties: 1) galactic plane (b=-0.1 deg) localization, 2) 150 msec duration, and 3) a blackbody rather than a simple power-law spectral shape (with a significance level of 97%). We found two possible X-ray counterparts of GRB 050925 by comparing the X-ray images from Swift XRT and XMM-Newton. Both X-ray sources show the transient behavior with a power-law decay index shallower than -1. We found no hard X-ray emission nor any additional burst from the location of GRB 050925 in approximately 5 Ms of INTEGRAL data. We discuss about the three BATSE short bursts which might be associated with GRB 050925, based on their location and the duration. Assuming GRB 050925 is associated with the H(sub II), regions (W 58) at the galactic longitude of 1=70 deg, we also discuss the source frame properties of GRB 050925.

  19. Computational model for short-fiber composites with eigenstrain formulation of boundary integral equations

    Institute of Scientific and Technical Information of China (English)

    MA Hang; XIA Li-wei; QIN Qing-hua

    2008-01-01

    A computational model is proposed for short-fiber reinforced materials with the eigenstrain formulation of the boundary integral equations(BIE)and solved with the newly developed boundary point method(BPM).The model is closely derived from the concept of the equivalent inclusion of Eshelby tensors.Eigenstrains are iteratively determined for each short.fiber embedded in the matrix with various properties via the Eshelby tensors,which can be readily obtained beforehand either through analytical or numerical means.As unknown variables appear only on the boundary of the solution domain,the solution scale of the inhomogeneity problem with the model is greatly reduced.This feature is considered significant because such a traditionally time-consuming problem with inhomogeneity can be solved most cost-effectively compared with existing numerical models of the FEM or the BEM.The numerical examples are presented to compute the overall elastic properties for various short-fiber reinforced composites over a representative volume element(RVE),showing the validity and the effectiveness of the proposed computational modal and the solution procedure.

  20. Integrated patient and tumor genetic testing for individualized cancer therapy.

    Science.gov (United States)

    Hertz, D L; McLeod, H L

    2016-02-01

    Tumor genome analysis is transforming cancer treatment by enabling identification of specific oncogenic drivers and selection of effective targeted agents. Meanwhile, patient genome analysis is being employed across therapeutic areas to inform selection of appropriate drugs and doses for treatment safety. Integration of patient genome analysis concurrent with preemptive tumor genetic testing will enable oncologists to make informed treatment decisions to select the right dose of the right drug for each patient and their tumor.

  1. Positive psychological functioning in breast cancer: An integrative review.

    Science.gov (United States)

    Casellas-Grau, Anna; Vives, Jaume; Font, Antoni; Ochoa, Cristian

    2016-06-01

    This integrative review aimed to analyze the research into positive psychological functioning after breast cancer, and to integrate the most relevant findings relating to sociodemographic, medical and psychosocial factors. Relevant outcomes were identified from electronic databases (Medline, PsycINFO, Web of Science, Scopus, Cochrane, CINAHL, and Wiley Online Library) up to July 2015. A Google search was performed to identify unindexed literature. Dissertations and theses were searched on Proquest Dissertations and Theses, DIALNET and TDX. Selection criteria included empirical studies assessing relationships between breast cancer and positive functioning, without restrictions on type of participants. In total, 134 studies met the inclusion criteria. The sociodemographic, medical, and psychosocial characteristics associated with well-being, posttraumatic growth, finding benefit and meaning were being young, undergoing chemotherapy, and having social support. The last two of these characteristics were time-oriented. The culture of the different samples and positive dispositional characteristics like optimism had an influence on the women's coping styles. Socioeconomic status and level of education were also associated with positive psychological functioning. The perceived impact of breast cancer on patient, as well as the perceived support from significant others can result in better functioning in women with breast cancer. The results highlight that oncology health professionals should take into account not only the individual and medical characteristics, but also the stage of the oncological process and the psychosocial environment of patients in order to promote their positive functioning.

  2. Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hui; Liu, Tao; Zhang, Zhen; Payne, Samuel H.; Zhang, Bai; McDermott, Jason E.; Zhou, Jian-Ying; Petyuk, Vladislav A.; Chen, Li; Ray, Debjit; Sun, Shisheng; Yang, Feng; Chen, Lijun; Wang, Jing; Shah, Punit; Cha, Seong Won; Aiyetan, Paul; Woo, Sunghee; Tian, Yuan; Gritsenko, Marina A.; Clauss, Therese R.; Choi, Caitlin; Monroe, Matthew E.; Thomas, Stefani; Nie, Song; Wu, Chaochao; Moore, Ronald J.; Yu, Kun-Hsing; Tabb, David L.; Fenyö, David; Bafna, Vineet; Wang, Yue; Rodriguez, Henry; Boja, Emily S.; Hiltke, Tara; Rivers, Robert C.; Sokoll, Lori; Zhu, Heng; Shih, Ie-Ming; Cope, Leslie; Pandey, Akhilesh; Zhang, Bing; Snyder, Michael P.; Levine, Douglas A.; Smith, Richard D.; Chan, Daniel W.; Rodland, Karin D.

    2016-07-01

    Ovarian cancer remains the most lethal gynecological malignancy in the developed world, despite recent advances in genomic information and treatment. To better understand this disease, define an integrated proteogenomic landscape, and identify factors associated with homologous repair deficiency (HRD) and overall survival, we performed a comprehensive proteomic characterization of ovarian high-grade serous carcinomas (HGSC) previously characterized by The Cancer Genome Atlas (TCGA). We observed that messenger RNA transcript abundance did not reliably predict abundance for 10,030 proteins across 174 tumors. Clustering of tumors based on protein abundance identified five subtypes, two of which correlated robustly with mesenchymal and proliferative subtypes, while tumors characterized as immunoreactive or differentiated at the transcript level were intermixed at the protein level. At the genome level, HGSC is characterized by a complex landscape of somatic copy number alterations (CNA), which individually do not correlate significantly with survival. Correlation of CNAs with protein abundances identified loci with significant trans regulatory effects mapping to pathways associated with proliferation, cell motility/invasion, and immune regulation, three known hallmarks of cancer. Using the trans regulated proteins we also created models significantly correlated with patient survival by multivariate analysis. Integrating protein abundance with specific post-translational modification data identified subnetworks correlated with HRD status; specifically, acetylation of Lys12 and Lys16 on histone H4 was associated with HRD status. Using quantitative phosphoproteomics data covering 4,420 proteins as reflective of pathway activity, we identified the PDGFR and VEGFR signaling pathways as significantly up-regulated in patients with short overall survival, independent of PDGFR and VEGFR protein levels, potentially informing the use of anti-angiogenic therapies. Components of

  3. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer.

    Science.gov (United States)

    Kamel, Azza M; Teama, Salwa; Fawzy, Amal; El Deftar, Mervat

    2016-06-01

    Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions.

  4. Short-Term Outcomes of Simultaneous Laparoscopic Colectomy and Hepatectomy for Primary Colorectal Cancer With Synchronous Liver Metastases

    OpenAIRE

    2014-01-01

    Although simultaneous resection of primary colorectal cancer and synchronous liver metastases is reported to be safe and effective, the feasibility of a laparoscopic approach remains controversial. This study evaluated the safety, feasibility, and short-term outcomes of simultaneous laparoscopic surgery for primary colorectal cancer with synchronous liver metastases. From September 2008 to December 2013, 10 patients underwent simultaneous laparoscopic resection of primary colorectal cancer an...

  5. Lie Algebraic Structures and Integrability of Long-Short Wave Equation in (2+1)Dimensions

    Institute of Scientific and Technical Information of China (English)

    ZHAOXue-Qing; LüJing-Fa

    2004-01-01

    The hidden symmetry and integrability of the long-short wave equation in (2+1) dimensions are considered using the prolongation approach. The internal algebraic structures and their linear spectra are derived in detail which show that the equation is integrable.

  6. Integrating short-term and long-term forecasting with reservoir optimisation; Mantaro Basin, Peru.

    Science.gov (United States)

    Jensen, R. A.; Lasarte, A.; Butts, M. B.

    2009-04-01

    Operational water management often requires a trade-off between short-term and long-term water demands, where short-term demands are driven for example by hydropower generation and flood protection requirements and the long-term demands by water and irrigation supply, sustainable reservoir management and the seasonal impacts of snow melt or climate. This paper presents an operational decision support system designed to forecast and optimise reservoir operations in both the short-term and long-term. The system has been established for the 20,000 km2 Mantaro river basin located in the high Andes with altitudes ranging from 3500 to nearly 6000 m.a.s.l.. The two main power stations at Tablachaca have a combined capacity of more than 1000 MW that supplies 30% of Peru's electrical energy. In addition, the basin's water resources supply extensive agricultural areas, an urban population and mining activities and sustain important ecological habitats. In this paper, the methodologies used for the integrating short-term and long-term forecasting are presented together with their application to the optimal operation of reservoirs. A key element in the system is the MIKE BASIN modelling tool. The system uses several modelling capabilities of MIKE BASIN: rainfall-runoff, reservoir operation, hydropower production, and river flow routing. The system also takes advantage of long-term forecasts (based on statistical information) and short-term forecasts (based on telemetry data). The continually updated runoff and flow forecasts enter the optimization, which applies the Model Predictive Control principle for MIKE BASIN as the core simulation model. For each optimization, a non-linear program algorithm is used to find the best release strategy. On the basis of the forecasted inflows and the real time data the system suggests to the user from which reservoirs to release water for alleviation of possible forecasted deficits. In addition to the Tablachaca scheme the model accounts for

  7. Integrated genomic and epigenomic analysis of breast cancer brain metastasis.

    Directory of Open Access Journals (Sweden)

    Bodour Salhia

    Full Text Available The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies.

  8. Integrated genomic and epigenomic analysis of breast cancer brain metastasis.

    Science.gov (United States)

    Salhia, Bodour; Kiefer, Jeff; Ross, Julianna T D; Metapally, Raghu; Martinez, Rae Anne; Johnson, Kyle N; DiPerna, Danielle M; Paquette, Kimberly M; Jung, Sungwon; Nasser, Sara; Wallstrom, Garrick; Tembe, Waibhav; Baker, Angela; Carpten, John; Resau, Jim; Ryken, Timothy; Sibenaller, Zita; Petricoin, Emanuel F; Liotta, Lance A; Ramanathan, Ramesh K; Berens, Michael E; Tran, Nhan L

    2014-01-01

    The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies.

  9. Integrable multi-component generalization of a modified short pulse equation

    Science.gov (United States)

    Matsuno, Yoshimasa

    2016-11-01

    We propose a multi-component generalization of the modified short pulse (SP) equation which was derived recently as a reduction of Feng's two-component SP equation. Above all, we address the two-component system in depth. We obtain the Lax pair, an infinite number of conservation laws and multisoliton solutions for the system, demonstrating its integrability. Subsequently, we show that the two-component system exhibits cusp solitons and breathers for which the detailed analysis is performed. Specifically, we explore the interaction process of two cusp solitons and derive the formula for the phase shift. While cusp solitons are singular solutions, smooth breather solutions are shown to exist, provided that the parameters characterizing the solutions satisfy certain conditions. Last, we discuss the relation between the proposed system and existing two-component SP equations.

  10. Catalog of Short Gamma-Ray Transients Detected in the SPI/INTEGRAL Experiment

    CERN Document Server

    Minaev, P Yu; Molkov, S V; Grebenev, S A

    2014-01-01

    We analyzed data obtained by the SPI telescope onboard the INTEGRAL observatory to search for short transient events with a duration from 1 ms to a few tens of seconds. An algorithm for identifying gamma-ray events against the background of a large number of charged particle interactions with the detector has been developed. The classification of events was made. Apart from the events associated with cosmic gamma-ray bursts (GRBs) confirmed by other space experiments and the activity of known soft gamma repeaters (for example, SGR 1806-20), previously unreported GRBs have been found. GRB candidates and short gamma-ray events probably associated with the activity of known SGRs and AXPs have been selected. The spectral evolution of 28 bright GRBs from the catalog has been studied extensively. A new method for investigating the spectral evolution is proposed. The energy dependence of the spectral lag for bursts with a simple structure of their light curves and for individual pulses of multipulse events is shown ...

  11. Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC.

    Directory of Open Access Journals (Sweden)

    Chad A Glazer

    Full Text Available BACKGROUND: Cancer/testis antigens (CTAs were first discovered as immunogenic targets normally expressed in germline cells, but differentially expressed in a variety of human cancers. In this study, we used an integrative epigenetic screening approach to identify coordinately expressed genes in human non-small cell lung cancer (NSCLC whose transcription is driven by promoter demethylation. METHODOLOGY/PRINCIPAL FINDINGS: Our screening approach found 290 significant genes from the over 47,000 transcripts incorporated in the Affymetrix Human Genome U133 Plus 2.0 expression array. Of the top 55 candidates, 10 showed both differential overexpression and promoter region hypomethylation in NSCLC. Surprisingly, 6 of the 10 genes discovered by this approach were CTAs. Using a separate cohort of primary tumor and normal tissue, we validated NSCLC promoter hypomethylation and increased expression by quantitative RT-PCR for all 10 genes. We noted significant, coordinated coexpression of multiple target genes, as well as coordinated promoter demethylation, in a large set of individual tumors that was associated with the SCC subtype of NSCLC. In addition, we identified 2 novel target genes that exhibited growth-promoting effects in multiple cell lines. CONCLUSIONS/SIGNIFICANCE: Coordinated promoter demethylation in NSCLC is associated with aberrant expression of CTAs and potential, novel candidate protooncogenes that can be identified using integrative discovery techniques. These findings have significant implications for discovery of novel CTAs and CT antigen directed immunotherapy.

  12. G-protein-coupled receptor for short-chain fatty acids suppresses colon cancer.

    Science.gov (United States)

    Tang, Yong; Chen, Yakun; Jiang, Hongmei; Robbins, Gregory T; Nie, Daotai

    2011-02-15

    GPR43 is a G-protein-coupled receptor for short-chain fatty acids (SCFAs). Expression of GPR43 is detected in hematopoietic tissues and the large intestine. SCFAs are derived from bacterial fermentation and metabolism of undigested dietary fibers and have been recognized for their cancer prevention activities in the colon. The role of SCFAs, particularly butyrate, in colon cancer therapy has been extensively studied, and its tumor suppressive functions are believed to be due to their intracellular actions, notably inhibition of histone deacetylase. In our study, we show that SCFAs also exert their antitumor effects via receptor GPR43 and that GPR43 is frequently lost in colon cancer cells. Immunohistostaining revealed that GPR43 immunoreactivity was high in normal colon tissues (N = 31) but was markedly reduced or completely lost in most colorectal adenocarcinoma tissues (N = 70) and their corresponding lymph node metastatic adenocarcinomas (N = 38). RT-PCR analysis detected the presence of full length GPR43 mRNA in only one (HT-29) of nine established human colon cancer cell lines. Restoration of GPR43 expression in HCT8 human colonic adenocarcinoma cells induced G0/G1 cell cycle arrest and activated caspases, leading to increased apoptotic cell death after propionate/butyrate treatment. Restored GPR43 expression, coupled with propionate treatment, induced an upregulation of p21 and a decrease in the levels of cyclin D3 and cyclin-dependent kinases (CDKs) 1 and 2, while the CDK4 and CDK6 levels remained unchanged. Our results suggest that GPR43 functions as a tumor suppressor by mediating SCFA-induced cell proliferation inhibition and apoptotic cell death in colon cancer.

  13. Professionalism in global, personalized cancer care: restoring authenticity and integrity.

    Science.gov (United States)

    Surbone, Antonella

    2013-01-01

    Personalized medicine is revolutionizing cancer care and creating new expectations among oncologists and patients. At present the benefit is still marginal, however, and must be understood as incremental. In addition, cultural and resource disparities limit the sustainability of new cancer therapies on a global scale. Adequate instruments are needed to enable our exercise of sound and honest judgment in distinguishing breakthrough treatments from those that yield only marginal or doubtful improvements, and to develop strategies for formulation and correct application of balanced guidelines for sustainable cancer care. Professionalism requires that the acquisition of knowledge and skills go hand in hand with moral education in the intellectual virtues of humility, perseverance, adaptability, communicativeness, and commitment to resist self-deception or conflicts of interest. Hidden curricula undermine the moral values of medicine: these must be understood and uncovered. We should possess a special body of knowledge, skills, and values that allow us to change our practices when appropriate and to be stewards of society's limited resources through proper communication with our patients and families. In the era of personalized oncology and global issues of sustainability, professional authenticity and integrity in cancer clinical practice are key to bridging the gaps between true and false expectations of patients and the public.

  14. EFFECTS OF SHORT TERM PRACTICE OF BHASTRIKA PRANAYAMA ON METABOLIC FITNESS (METF AND BONE INTEGRITY (BI

    Directory of Open Access Journals (Sweden)

    Baljinder Singh Bal

    2015-07-01

    Full Text Available Purpose: The present study was conducted with the objective to determine the short term practice of bhastrika pranayama on Metabolic Fitness and Bone Integrity. Material: 30 university level females between the age group of 21-26 years were selected. The subjects were randomly matched and assigned into two groups: Group-A: Experimental (n 1=15; Group-B: Control (n 2=15. The subjects from Group-A: Experimental were provided to a 4-weeks bhastrika pranayama. Statistical Analysis: Student t test for paired samples was utilized to compare the means of the pre-test and the post-test. Results & Conclusions: Based on the analysis of the results obtained, we conclude that the significant differences were found in Metabolic Fitness (i.e., Maximal Oxygen Consumption (V O2max and blood pressure of University Level Girls. Insignificant between-group differences were noted in Blood Lipid, Blood Sugar and Bone Integrity of University Level Girls.

  15. Multidensity integral-equation theory for short diblock hard-sphere-sticky-hard-sphere chains.

    Science.gov (United States)

    Wu, Ning; Chiew, Y C

    2010-04-01

    The multidensity Ornstein-Zernike integral equation theory is applied to study a simple model of hard sphere/sticky hard sphere diblock chains. The multidensity integral equation formalism has been successfully used to model the equilibrium structure and thermodynamic properties of homonuclear chains and shorter dimer fluids; to our knowledge it has not been applied to model diblock chains. In this work, a diblock chain fluids is represented by an m-component equal molar mixture of hard spheres with species 1,2,...,mh and sticky hard spheres with species mh+1,mh+2,...,m. Each spherical particle has two attractive sites A and B except species 1 and m, which have only one site per particle. In the limit of complete association, this mixture yields a system of monodisperse diblock chains. A general solution of this model is obtained in the Percus-Yevick, Polymer Percus-Yevick and ideal chain approximations. Both structural and thermodynamic properties of this model are investigated. From this study, a microphase separation is predicted for relatively short diblock symmetric and asymmetric chains. This microphase separation is enhanced at lower temperature and higher density. When chain length increases, the phase transition changes from a microphase level to a macrophase level. The size of microdomain structure is found to be dependent on total chain length, relative ratio of block lengths, temperature, and density.

  16. Monolithically integrated quantum dot optical modulator with Semiconductor optical amplifier for short-range optical communications

    Science.gov (United States)

    Yamamoto, Naokatsu; Akahane, Kouichi; Umezawa, Toshimasa; Kawanishi, Tetsuya

    2015-04-01

    A monolithically integrated quantum dot (QD) optical gain modulator (OGM) with a QD semiconductor optical amplifier (SOA) was successfully developed. Broadband QD optical gain material was used to achieve Gbps-order high-speed optical data transmission, and an optical gain change as high as approximately 6-7 dB was obtained with a low OGM voltage of 2.0 V. Loss of optical power due to insertion of the device was also effectively compensated for by the SOA section. Furthermore, it was confirmed that the QD-OGM/SOA device helped achieve 6.0-Gbps error-free optical data transmission over a 2.0-km-long photonic crystal fiber. We also successfully demonstrated generation of Gbps-order, high-speed, and error-free optical signals in the >5.5-THz broadband optical frequency bandwidth larger than the C-band. These results suggest that the developed monolithically integrated QD-OGM/SOA device will be an advantageous and compact means of increasing the usable optical frequency channels for short-reach communications.

  17. Integration of interventional bronchoscopy in the management of lung cancer

    Directory of Open Access Journals (Sweden)

    Nicolas Guibert

    2015-09-01

    Full Text Available Tracheal or bronchial proximal stenoses occur as complications in 20–30% of lung cancers, resulting in a dramatic alteration in quality of life and poor prognosis. Bronchoscopic management of these obstructions is based on what are known as “thermal” techniques for intraluminal stenosis and/or placement of tracheal or bronchial prostheses for extrinsic compressions, leading to rapid symptom palliation in the vast majority of patients. This invasive treatment should only be used in cases of symptomatic obstructions and in the presence of viable bronchial tree and downstream parenchyma. This review aims to clarify 1 the available methods for assessing the characteristics of stenoses before treatment, 2 the various techniques available including their preferred indications, outcomes and complications, and 3 the integration of interventional bronchoscopy in the multidisciplinary management of proximal bronchial cancers and its synergistic effects with the other specific treatments (surgery, radiotherapy or chemotherapy.

  18. Integration of interventional bronchoscopy in the management of lung cancer.

    Science.gov (United States)

    Guibert, Nicolas; Mazieres, Julien; Marquette, Charles-Hugo; Rouviere, Damien; Didier, Alain; Hermant, Christophe

    2015-09-01

    Tracheal or bronchial proximal stenoses occur as complications in 20-30% of lung cancers, resulting in a dramatic alteration in quality of life and poor prognosis. Bronchoscopic management of these obstructions is based on what are known as "thermal" techniques for intraluminal stenosis and/or placement of tracheal or bronchial prostheses for extrinsic compressions, leading to rapid symptom palliation in the vast majority of patients. This invasive treatment should only be used in cases of symptomatic obstructions and in the presence of viable bronchial tree and downstream parenchyma. This review aims to clarify 1) the available methods for assessing the characteristics of stenoses before treatment, 2) the various techniques available including their preferred indications, outcomes and complications, and 3) the integration of interventional bronchoscopy in the multidisciplinary management of proximal bronchial cancers and its synergistic effects with the other specific treatments (surgery, radiotherapy or chemotherapy).

  19. Lymphoscintigraphy in breast cancer: a short review about the impact on upper limb after surgical treatment

    Energy Technology Data Exchange (ETDEWEB)

    Bergmann, Anke; Resende, Juliana Miranda Dutra de; Bello, Marcelo Adeodato; Oliveira, Juliana Flavia de; Bernardo-Filho, Mario [Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil); Santos-Filho, Sebastiao David [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Lab. de Radiofarmacia Experimental; Palestro, Christopher J. [Yeshiva University, NY (United States). Albert Einstein College of Medicine

    2008-12-15

    Breast cancer is still associated with high mortality rates and one of the most important factors governing long survival is accurate and early diagnosis. In underdeveloped countries, this disease frequently is only detected in advanced stages; however, through mammography, many women have been diagnosed at early stages. In this context, the sentinel lymph node (SLN) technique is associated with less postoperative morbidity compared to axillary lymphadenectomy. Lymphoscintigraphy has emerged as a method for the evaluation of lymphatic drainage chains in various tumours, being both accurate and non invasive. The aim of this work is to present the main aspects which cause controversy about SLN and lymphoscintigraphy and the impact that these procedures have had on lymphedema after surgical treatment for breast cancer. A short review including papers in English, Spanish and Portuguese, available on Lilacs and Medline database, published between January, 2000 and July, 2008 was performed. The key words breast cancer, lymphoscintigraphy, SLN biopsy, lymphedema were used. Various studies have aimed to compare the incidence and prevalence of lymphedema according to the technique used; however, the population subjected to SLN is different from the one with indication for axillary lymphadenectomy regarding staging. Moreover, little is known about long term morbidity since it is a relatively new technique. In conclusion, the development of surgical techniques has permitted to minimize deformities and the current trend is that these techniques be as conservative as possible. Thus, lymphoscintigraphy plays an important role in the identification of SLN, contributing to the prevention and minimization of postoperative complications. (author)

  20. Short telomere length and breast cancer risk: a study in sister sets.

    Science.gov (United States)

    Shen, Jing; Terry, Mary Beth; Gurvich, Irina; Liao, Yuyan; Senie, Ruby T; Santella, Regina M

    2007-06-01

    Telomeres consist of a tandem repeats of the sequence TTAGGG at the ends of chromosomes and play a key role in the maintenance of chromosomal stability. Previous studies indicated that short telomeres are associated with increased risk for human bladder, head and neck, lung, and renal cell cancer. We investigated the association between white blood cell telomere length and breast cancer risk among 268 family sets (287 breast cancer cases and 350 sister controls). Telomere length was assessed by quantitative PCR. The mean telomere length was shorter in cases (mean, 0.70; range, 0.03-1.95) than in unaffected control sisters (mean, 0.74; range, 0.03-2.29), but no significant difference was observed (P = 0.11). When subjects were categorized according to the median telomere length in controls (0.70), affected sisters had shorter telomeres compared with unaffected sisters after adjusting for age at blood donation and smoking status [odds ratio (OR), 1.3; 95% confidence interval (95% CI), 0.9-1.8], but the association was not statistically significant. The association by quartile of telomere length (Q4 shortest versus Q1 longest) also supported an increase in risk from shorter telomere length, although the association was not statistically significant (OR, 1.6; 95% CI, 0.9-2.7). This association was more pronounced among premenopausal women (OR, 2.1; 95% CI, 0.8-5.5) than postmenopausal women (OR, 1.3; 95% CI, 0.5-3.6 for Q4 versus Q1). If these associations are replicated in larger studies, they provide modest epidemiologic evidence that shortened telomere length may be associated with breast cancer risk.

  1. Integrative cancer care in a US academic cancer centre: The Memorial Sloan-Kettering Experience.

    Science.gov (United States)

    Deng, G

    2008-08-01

    Various surveys show that interest in complementary and alternative medicine (CAM) is high among cancer patients. Patients want to explore all options that may help their treatment. Many CAM modalities offer patients an active role in their self-care, and the resulting sense of empowerment is very appealing. On the other hand, many unscrupulous marketeers promote alternative cancer "cures," targeting cancer patients who are particularly vulnerable. Some alternative therapies can hurt patients by delaying effective treatment or by causing adverse effects or detrimental interactions with other medications. It is not in the best interest of cancer patients if they cannot get appropriate guidance on the use of CAM from the health care professionals who are part of their cancer care team. The Integrative Medicine Service at Memorial Sloan-Kettering Cancer Center in New York was established in 1999 to address patient interest in cam, to incorporate helpful complementary therapies into each patient's overall treatment management, to guide patients in avoiding harmful alternative therapies, and to develop prospective research to evaluate the efficacy of CAM modalities.

  2. Integrative Cancer Care in a US Academic Cancer Centre: The Memorial Sloan–Kettering Experience

    Science.gov (United States)

    Deng, G.

    2008-01-01

    Various surveys show that interest in complementary and alternative medicine (cam) is high among cancer patients. Patients want to explore all options that may help their treatment. Many cam modalities offer patients an active role in their self-care, and the resulting sense of empowerment is very appealing. On the other hand, many unscrupulous marketeers promote alternative cancer “cures,” targeting cancer patients who are particularly vulnerable. Some alternative therapies can hurt patients by delaying effective treatment or by causing adverse effects or detrimental interactions with other medications. It is not in the best interest of cancer patients if they cannot get appropriate guidance on the use of cam from the health care professionals who are part of their cancer care team. The Integrative Medicine Service at Memorial Sloan–Kettering Cancer Center in New York was established in 1999 to address patient interest in cam, to incorporate helpful complementary therapies into each patient’s overall treatment management, to guide patients in avoiding harmful alternative therapies, and to develop prospective research to evaluate the efficacy of cam modalities. PMID:18769574

  3. Methodology to predict long-term cancer survival from short-term data using Tobacco Cancer Risk and Absolute Cancer Cure models

    Science.gov (United States)

    Mould, R. F.; Lederman, M.; Tai, P.; Wong, J. K. M.

    2002-11-01

    Three parametric statistical models have been fully validated for cancer of the larynx for the prediction of long-term 15, 20 and 25 year cancer-specific survival fractions when short-term follow-up data was available for just 1-2 years after the end of treatment of the last patient. In all groups of cases the treatment period was only 5 years. Three disease stage groups were studied, T1N0, T2N0 and T3N0. The models are the Standard Lognormal (SLN) first proposed by Boag (1949 J. R. Stat. Soc. Series B 11 15-53) but only ever fully validated for cancer of the cervix, Mould and Boag (1975 Br. J. Cancer 32 529-50), and two new models which have been termed Tobacco Cancer Risk (TCR) and Absolute Cancer Cure (ACC). In each, the frequency distribution of survival times of defined groups of cancer deaths is lognormally distributed: larynx only (SLN), larynx and lung (TCR) and all cancers (ACC). All models each have three unknown parameters but it was possible to estimate a value for the lognormal parameter S a priori. By reduction to two unknown parameters the model stability has been improved. The material used to validate the methodology consisted of case histories of 965 patients, all treated during the period 1944-1968 by Dr Manuel Lederman of the Royal Marsden Hospital, London, with follow-up to 1988. This provided a follow-up range of 20- 44 years and enabled predicted long-term survival fractions to be compared with the actual survival fractions, calculated by the Kaplan and Meier (1958 J. Am. Stat. Assoc. 53 457-82) method. The TCR and ACC models are better than the SLN model and for a maximum short-term follow-up of 6 years, the 20 and 25 year survival fractions could be predicted. Therefore the numbers of follow-up years saved are respectively 14 years and 19 years. Clinical trial results using the TCR and ACC models can thus be analysed much earlier than currently possible. Absolute cure from cancer was also studied, using not only the prediction models which

  4. Integrating Multiscale Modeling with Drug Effects for Cancer Treatment.

    Science.gov (United States)

    Li, Xiangfang L; Oduola, Wasiu O; Qian, Lijun; Dougherty, Edward R

    2015-01-01

    In this paper, we review multiscale modeling for cancer treatment with the incorporation of drug effects from an applied system's pharmacology perspective. Both the classical pharmacology and systems biology are inherently quantitative; however, systems biology focuses more on networks and multi factorial controls over biological processes rather than on drugs and targets in isolation, whereas systems pharmacology has a strong focus on studying drugs with regard to the pharmacokinetic (PK) and pharmacodynamic (PD) relations accompanying drug interactions with multiscale physiology as well as the prediction of dosage-exposure responses and economic potentials of drugs. Thus, it requires multiscale methods to address the need for integrating models from the molecular levels to the cellular, tissue, and organism levels. It is a common belief that tumorigenesis and tumor growth can be best understood and tackled by employing and integrating a multifaceted approach that includes in vivo and in vitro experiments, in silico models, multiscale tumor modeling, continuous/discrete modeling, agent-based modeling, and multiscale modeling with PK/PD drug effect inputs. We provide an example application of multiscale modeling employing stochastic hybrid system for a colon cancer cell line HCT-116 with the application of Lapatinib drug. It is observed that the simulation results are similar to those observed from the setup of the wet-lab experiments at the Translational Genomics Research Institute.

  5. Efficacy and safety assessment of short EOF program regional arterial infusion chemotherapy and conventional chemotherapy for advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ming-Cai Shui; Lin Xiong

    2016-01-01

    Objective:To study the efficacy and safety of short EOF program regional arterial infusion chemotherapy and conventional chemotherapy for advanced gastric cancer.Methods: 66 cases of patients diagnosed of advanced gastric cancer in our hospital were enrolled for study, given preoperative short EOF program chemotherapy and randomly divided into two groups. Observation group received short EOF program regional arterial infusion chemotherapy and control group received short EOF program intravenous chemotherapy. Then number of apoptosis cells and contents of apoptosis genes in the tumor tissue, serum liver and kidney function indicators as well as cfDNA methylation degree of two groups were detected. Results:(1) indicators of efficacy: the number of apoptosis cells in gastric cancer tissue of observation group was more than that of control group, mRNA levels of Caspase-3, Caspase-9, Fas and FasL were higher than those of control group, and serum p16, RNF180, SFRP2, SOX17 and RUNX methylation ratios were lower than those of control group; (2) indicators of safety: serum RBP, CysC, ALT and AST contents of observation group were lower than those of control group.Conclusions:Short EOF program regional arterial infusion chemotherapy can more effectively kill cancer cells, reduce methylation degree of tumor-associated genes and decrease liver function and kidney function damage; both efficacy and safety of it are better than conventional chemotherapy.

  6. Short-term and long-term risk factors in gastric cancer.

    Science.gov (United States)

    Verlato, Giuseppe; Marrelli, Daniele; Accordini, Simone; Bencivenga, Maria; Di Leo, Alberto; Marchet, Alberto; Petrioli, Roberto; Zoppini, Giacomo; Muggeo, Michele; Roviello, Franco; de Manzoni, Giovanni

    2015-06-07

    While in chronic diseases, such as diabetes, mortality rates slowly increases with age, in oncological series mortality usually changes dramatically during the follow-up, often in an unpredictable pattern. For instance, in gastric cancer mortality peaks in the first two years of follow-up and declines thereafter. Also several risk factors, such as TNM stage, largely affect mortality in the first years after surgery, while afterward their effect tends to fade. Temporal trends in mortality were compared between a gastric cancer series and a cohort of type 2 diabetic patients. For this purpose, 937 patients, undergoing curative gastrectomy with D1/D2/D3 lymphadenectomy for gastric cancer in three GIRCG (Gruppo Italiano Ricerca Cancro Gastrico = Italian Research Group for Gastric Cancer) centers, were compared with 7148 type 2 diabetic patients from the Verona Diabetes Study. In the early/advanced gastric cancer series, mortality from recurrence peaked to 200 deaths per 1000 person-years 1 year after gastrectomy and then declined, becoming lower than 40 deaths per 1000 person-years after 5 years and lower than 20 deaths after 8 years. Mortality peak occurred earlier in more advanced T and N tiers. At variance, in the Verona diabetic cohort overall mortality slowly increased during a 10-year follow-up, with ageing of the type 2 diabetic patients. Seasonal oscillations were also recorded, mortality being higher during winter than during summer. Also the most important prognostic factors presented a different temporal pattern in the two diseases: while the prognostic significance of T and N stage markedly decrease over time, differences in survival among patients treated with diet, oral hypoglycemic drugs or insulin were consistent throughout the follow-up. Time variations in prognostic significance of main risk factors, their impact on survival analysis and possible solutions were evaluated in another GIRCG series of 568 patients with advanced gastric cancer, undergoing

  7. An Evaluation Methodology for Longitudinal Studies of Short-Term Cancer Research Training Programs.

    Science.gov (United States)

    Padilla, Luz A; Venkatesh, Raam; Daniel, Casey L; Desmond, Renee A; Brooks, C Michael; Waterbor, John W

    2016-03-01

    The need to familiarize medical students and graduate health professional students with research training opportunities that cultivate the appeal of research careers is vital to the future of research. Comprehensive evaluation of a cancer research training program can be achieved through longitudinal tracking of program alumni to assess the program's impact on each participant's career path and professional achievements. With advances in technology and smarter means of communication, effective ways to track alumni have changed. In order to collect data on the career outcomes and achievements of nearly 500 short-term cancer research training program alumni from 1999-2013, we sought to contact each alumnus to request completion of a survey instrument online, or by means of a telephone interview. The effectiveness of each contact method that we used was quantified according to ease of use and time required. The most reliable source of contact information for tracking alumni from the early years of the program was previous tracking results, and for alumni from the later years, the most important source of contact information was university alumni records that provided email addresses and telephone numbers. Personal contacts with former preceptors were sometimes helpful, as were generic search engines and people search engines. Social networking was of little value for most searches. Using information from two or more sources in combination was most effective in tracking alumni. These results provide insights and tools for other research training programs that wish to track their alumni for long-term program evaluation.

  8. Li-ion Battery Separators, Mechanical Integrity and Failure Mechanisms Leading to Soft and Hard Internal Shorts

    Science.gov (United States)

    Zhang, Xiaowei; Sahraei, Elham; Wang, Kai

    2016-09-01

    Separator integrity is an important factor in preventing internal short circuit in lithium-ion batteries. Local penetration tests (nail or conical punch) often produce presumably sporadic results, where in exactly similar cell and test set-ups one cell goes to thermal runaway while the other shows minimal reactions. We conducted an experimental study of the separators under mechanical loading, and discovered two distinct deformation and failure mechanisms, which could explain the difference in short circuit characteristics of otherwise similar tests. Additionally, by investigation of failure modes, we provided a hypothesis about the process of formation of local “soft short circuits” in cells with undetectable failure. Finally, we proposed a criterion for predicting onset of soft short from experimental data.

  9. Measurement properties of PROMIS Sleep Disturbance short forms in a large, ethnically diverse cancer cohort

    Directory of Open Access Journals (Sweden)

    Roxanne E. Jensen

    2016-06-01

    Full Text Available AIMS: To evaluate model fit, differential item function (DIF, and construct validity of select short forms from the PROMIS® Sleep Disturbance item bank. METHODS: We recruited cancer survivors who were between 6 - 13 months post diagnosis (n = 4,956, as part of the Measuring Your Health (MY-Health study. We measured sleep disturbance using 10 items commonly found in PROMIS Sleep Disturbance short forms (Sleep 4a, Sleep 6a, Sleep 8b, and which are frequently administered in computerized adaptive testing. We evaluated domain reliability using Cronbach’s coefficient alpha and factorial validity by fitting a PROMIS Sleep Disturbance unidimensional measurement model using confirmatory factor analy-sis (CFA. At the item-level, we examined DIF with respect to race/ethnicity (non-Hispanic White [NHW], non-Hispanic Black [NHB], Hispanic, and Asian/Pacific Islander, age, and sex. We used a multi-group CFA and multiple indicators, multiple methods (MIMIC analyses. We then assessed construct validity (convergent, discriminate, and known groups for sleep short forms, and a new “best fit” 6-item sleep disturbance short form. RESULTS: We identified a satisfactory unidimensional sleep disturbance 6-item measure (χ2(637.6, p < 0.001, RMSEA = 0.031. To achieve this, we removed four items from the model with item content overlap and added residual covariances between positively worded items in order to address a method effect. We identified one instance of DIF: NHW participants were less likely to agree with the statement “I had difficulty falling asleep” compared to NHBs, Hispanics, or Asians/Pacific Islanders, who all reported the same level of sleep disturbance. After controlling for DIF, we extended this into a MIMIC model, identifying no additional DIF by age or sex. Across all race/ethnicity groups, the adjusted overall means suggest that older adults reported significantly lower sleep disturbance, and NHW, NHB, and Hispanic women reported

  10. Tumor perfusion increases during hypofractionated short-course radiotherapy in rectal cancer : Sequential perfusion-CT findings

    NARCIS (Netherlands)

    Janssen, Marco H. M.; Aerts, Hugo J. W. L.; Kierkels, Roel G. J.; Backes, Walter H.; Ollers, Michel C.; Buijsen, Jeroen; Lambin, Philippe; Lammering, Guido

    2010-01-01

    Purpose: The purpose of this study was to investigate perfusion of rectal tumors and to determine early responses to short-course hypofractionated radiotherapy (RT). Material and methods: Twenty-three rectal cancer patients were included, which underwent perfusion-CT imaging before (pre-scan) and af

  11. Tissue-Doppler assessment of cardiac left ventricular function during short-term adjuvant epirubicin therapy for breast cancer

    DEFF Research Database (Denmark)

    Appel, Jon M; Sogaard, Peter; Mortensen, Christiane E;

    2011-01-01

    It has been hypothesized that the extent of acute anthracycline-induced cardiotoxicity reflects the risk for late development of heart failure. The aim of this study was to examine if short-term changes in cardiac function can be detected even after low-dose adjuvant epirubicin therapy for breast...... cancer when using Doppler tissue imaging of longitudinal left ventricular function....

  12. Esophageal Cancer Dose Escalation Using a Simultaneous Integrated Boost Technique

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, James, E-mail: jwelsh@mdanderson.org [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Palmer, Matthew B. [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Ajani, Jaffer A. [Department of Gastrointestinal Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Liao Zhongxing [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Swisher, Steven G.; Hofstetter, Wayne L. [Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States); Allen, Pamela K.; Settle, Steven H.; Gomez, Daniel; Likhacheva, Anna; Cox, James D.; Komaki, Ritsuko [Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX (United States)

    2012-01-01

    Purpose: We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer. Methods and Materials: Treatment plans were generated using four different approaches (two-dimensional conformal radiotherapy [2D-CRT] to 50.4 Gy, 2D-CRT to 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure. Results: The 50.4 Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4 Gy 2D-CRT plan. The 64.8 Gy SIB-IMRT plan produced a 28% increase in GTV dose and comparable normal tissue doses as the 50.4 Gy IMRT plan; compared with the 50.4 Gy 2D-CRT plan, the 64.8 Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord). Conclusions: The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation.

  13. Risk factors of breast cancer and knowledge about the disease: an integrative revision of Latin American studies

    Directory of Open Access Journals (Sweden)

    Aline Ferreira de Araújo Jerônimo

    Full Text Available Abstract The aim of this integrative review was to compare Latin American literature about risk and knowledge on breast cancer. Of 47 studies selected, 20 were about knowledge or awareness and 27 about risk of breast cancer. English was the dominant language in studies about risk, whereas studies about knowledge were mainly written in Spanish or Portuguese. Studies about knowledge were all cross- sectional, whereas case- control studies dominated authors’ interest about risk of breast cancer. Studies about knowledge were mainly focused on early detection of the disease and the most common study objective was breast self- examination (N = 14. In contrast, few studies about risk of breast cancer focused on early detection (N = 5. Obesity and overweight (N = 14, family history (N = 13, decreased parity (N = 12, and short breastfeeding duration (N = 10 were among the most frequent identified risk factors. Socio- economic factors such as income and educational level had variable effects on breast cancer risk and affected also knowledge of women about risk factors and early detection. Present results indicated that studies about risk of breast cancer were more often based on a better sound analytical background, compared to studies about knowledge, which were mostly descriptive.

  14. Integrated proteomic analysis of human cancer cells and plasma from tumor bearing mice for ovarian cancer biomarker discovery.

    Directory of Open Access Journals (Sweden)

    Sharon J Pitteri

    Full Text Available The complexity of the human plasma proteome represents a substantial challenge for biomarker discovery. Proteomic analysis of genetically engineered mouse models of cancer and isolated cancer cells and cell lines provide alternative methods for identification of potential cancer markers that would be detectable in human blood using sensitive assays. The goal of this work is to evaluate the utility of an integrative strategy using these two approaches for biomarker discovery.We investigated a strategy that combined quantitative plasma proteomics of an ovarian cancer mouse model with analysis of proteins secreted or shed by human ovarian cancer cells. Of 106 plasma proteins identified with increased levels in tumor bearing mice, 58 were also secreted or shed from ovarian cancer cells. The remainder consisted primarily of host-response proteins. Of 25 proteins identified in the study that were assayed, 8 mostly secreted proteins common to mouse plasma and human cancer cells were significantly upregulated in a set of plasmas from ovarian cancer patients. Five of the eight proteins were confirmed to be upregulated in a second independent set of ovarian cancer plasmas, including in early stage disease.Integrated proteomic analysis of cancer mouse models and human cancer cell populations provides an effective approach to identify potential circulating protein biomarkers.

  15. Application of integrative information system improves the quality and effectiveness of cancer case management

    Science.gov (United States)

    Lee, Pei-Yi; Chang, Tsue-Rung

    2015-01-01

    Cancer case management provides consecutive care during the entire process through diagnosis to treatment and follow-up. We established an integrative information system with integration of the health information system. This integrative information system shortened the time spent on case screening, follow-up data management, and monthly data summarization of case managers. It also promoted the case follow-up rate. This integrative information system may improve the quality and effectiveness for cancer case management, one important part of cancer nursing. PMID:26089680

  16. Motexafin lutetium-photodynamic therapy of prostate cancer: Short and long term effects on PSA

    Science.gov (United States)

    Patel, Hiral; Mick, Rosemarie; Finlay, Jarod; Zhu, Timothy C.; Rickter, Elizabeth; Cengel, Keith A.; Malkowicz, S. Bruce; Hahn, Stephen M.; Busch, Theresa M.

    2009-01-01

    Purpose: The time course of serum PSA response to photodynamic therapy (PDT) of prostate cancer was measured. Experimental Design: Seventeen patients were treated in a Phase I trial of motexafin lutetium-PDT. PDT dose was calculated in each patient as the product of the ex vivo-measured pre-PDT photosensitizer level and the in situ-measured light dose. Serum PSA level was measured within two months prior to PDT (baseline), and at day 1; weeks 1-3; months 1, 2 and 3; months 4-6 and months 7-11 after PDT. Results: At 24h after PDT, serum PSA increased by 98±36% (mean ± SE) relative to baseline levels (p=0.007). When patients were dichotomized based on median PDT dose, those who received high PDT dose demonstrated a 119±52% increase in PSA compared to a 54±27% increase in patients treated at low PDT dose. Patients treated with high vs. low PDT dose demonstrated a median biochemical delay of 82 vs. 43 days (p=0.024), with biochemical delay defined as the length of time between PDT and a nonreversible increase in PSA to a value ≥baseline. Conclusions: Results show PDT to induce large, transient increases in serum PSA levels. Patients who experienced high PDT dose demonstrated greater short-term increase in PSA and a significantly more durable PSA response (biochemical delay). These data strongly promote the need for individualized delivery of PDT dose and assessment of treatment effect in PDT of prostate cancer. Information gained from such patient-specific measurements could facilitate the introduction of multiple PDT sessions in patients who would benefit. PMID:18676760

  17. Development of the short version of the Gynecologic Cancer Lymphedema Questionnaire: GCLQ-7

    Science.gov (United States)

    Kim, Namjoo; Lee, Seonjoo; Lee, Sujung; Seo, Sang-Soo; Chung, Seung Hyun

    2017-01-01

    Objective The Gynecologic Cancer Lymphedema Questionnaire (GCLQ) was designed to identify gynecologic cancer patients with lower limb lymphedema (LLL). The questionnaire consists of 20 items distributed over 7 symptom clusters. The present study aimed to develop an abridged form of the GCLQ for simpler screening and more effective follow-up of LLL. Methods Data that had been collected for the development and validation of the Korean version of the GCLQ (GCLQ-K) were used in this study. Receiver-operating characteristic (ROC) curves were drawn according to the individual items of the GCLQ-K. Based on discrimination ability, the candidate items were selected in each symptom cluster. After combining the items, the best model was identified and named GCLQ-7. The area under the ROC curve (AUC) was compared between the GCLQ-7 and the original GCLQ-K. Results In total, 11 candidate items were selected from the original GCLQ-K. Among the models made with the candidate items, GCLQ-7, the best model, was constructed with 7 items as follows: 1) limited knee movement, 2) general swelling, 3) redness, 4) firmness/tightness, 5) groin swelling, 6) heaviness, and 7) aching. This model exhibited an AUC of 0.945 (95% confidence interval [CI], 0.900–0.991), which is comparable with that of the original GCLQ-K (AUC, 0.867; 95% CI, 0.779–0.956). The best cutoff value was 2 points, at which the sensitivity and specificity were 97.0% and 76.5%, respectively. Conclusion The newly developed short version model, GCLQ-7, showed acceptable discrimination ability as compared with the original GCLQ-K. PMID:27819411

  18. Short-term outcomes of simultaneous laparoscopic colectomy and hepatectomy for primary colorectal cancer with synchronous liver metastases.

    Science.gov (United States)

    Inoue, Akira; Uemura, Mamoru; Yamamoto, Hirofumi; Hiraki, Masayuki; Naito, Atsushi; Ogino, Takayuki; Nonaka, Ryoji; Nishimura, Junichi; Wada, Hiroshi; Hata, Taishi; Takemasa, Ichiro; Eguchi, Hidetoshi; Mizushima, Tsunekazu; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki

    2014-01-01

    Although simultaneous resection of primary colorectal cancer and synchronous liver metastases is reported to be safe and effective, the feasibility of a laparoscopic approach remains controversial. This study evaluated the safety, feasibility, and short-term outcomes of simultaneous laparoscopic surgery for primary colorectal cancer with synchronous liver metastases. From September 2008 to December 2013, 10 patients underwent simultaneous laparoscopic resection of primary colorectal cancer and synchronous liver metastases with curative intent at our institute. The median operative time was 452 minutes, and the median estimated blood loss was 245 mL. Median times to discharge from the hospital and adjuvant chemotherapy were 13.5 and 44 postoperative days, respectively. Negative resection margins were achieved in all cases, with no postoperative mortality or major morbidity. Simultaneous laparoscopic colectomy and hepatectomy for primary colorectal cancer with synchronous liver metastases appears feasible with low morbidity and favorable outcomes.

  19. Short-Term Side Effects after Radioiodine Treatment in Patients with Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Liyan Lu

    2016-01-01

    Full Text Available Objectives. I-131 therapy for differentiated thyroid cancer (DTC could induce adverse effects. The purpose of this study was to report and analyze symptoms after I-131 treatment within the hospitalization and present relevant medical intervention. Methods. I-131 doses ranging from 3.7 to 9.25 GBq (100–250 mCi were administrated for thyroid remnant ablation or treating DTC metastases. 117 patients with DTC for I-131 therapy were monitored through the video and intercommunicating with standardized questionnaire at different time points after I-131 oral administration. Adverse effects were recorded and relevant clinical factors were analyzed. Results. Among all the 117 patients, 55 cases complained of neck’s pain or swelling and 79 cases presented with gastrointestinal symptoms. Pain or swelling of salivary gland occurred in 15 patients, headache and vertigo in 10, insomnia in 9, vocal cord paralysis in 6, fatigue or general malaise in 6, and foreign body sensation in 5. Body numbness and urinary symptoms were observed in only 1 case, respectively. Those side effects were related with sex, pre-I-131 treatment TSH levels, frequency of I-131 therapy, and lymph node metastases. Conclusions. Short-term side effects after I-131 therapy for DTC patients varied individually; severe symptoms were not uncommon but generally did not need emergent medical intervention.

  20. Risk factors for short-term outcomes after thoracoscopic lobectomy for lung cancer.

    Science.gov (United States)

    Irie, Masataka; Nakanishi, Ryoichi; Yasuda, Manabu; Fujino, Yoshihisa; Hamada, Kazumi; Hyodo, Masahiro

    2016-08-01

    Few studies have analysed postoperative risk factors in patients undergoing thoracoscopic lobectomy, including assessments of preoperative physical function. The objectives of this study were to identify predictors of postoperative deterioration of performance status and cardiopulmonary complications in cases of thoracoscopic lobectomy.Between June 2005 and October 2012, we retrospectively reviewed 188 consecutive subjects who underwent thoracoscopic lobectomy for preoperative stage I nonsmall cell lung cancer. The demographic and clinical parameters, including physical function, were analysed using a multivariate logistic regression to clarify the determinants.The percent predicted diffusing capacity of the lung for carbon monoxide, quadriceps muscle strength and pathologic stage were independent risk factors for deterioration of performance status after surgery in the multivariate analyses. Chronic obstructive pulmonary disease, 6-min walking distance and pathologic stage were also independent risk factors for postoperative cardiopulmonary complications.Our data suggest that, in addition to a greater pathologic stage, lower diffusing capacity and comorbid chronic obstructive pulmonary disease, poor physical function was associated with worse short-term outcomes after thoracoscopic lobectomy. An evaluation of preoperative quadriceps muscle strength and 6-min walk test is easily performed and may therefore be a useful predictor in cases of thoracoscopic lobectomy.

  1. Thyroid cancer in the Marshallese: relative risk of short-lived internal emitters and external radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Lessard, E.T.; Brill, A.B.; Adams, W.H.

    1985-01-01

    In a study of the comparative effects of internal versus external irradiation of the thyroid in young people, we determined that the dose from internal irradiation of the thyroid with short-lived internal emitters produced several times less thyroid cancer than did the same dose of radiation given externally. We determined this finding for a group of 85 Marshall Islands children, who were less than 10 years of age at the time of exposure and who were accidentially exposed to internal and external thyroid radiation at an average level of 1400 rad. The external risk coefficient ranged between 2.5 and 4.9 cancers per million person-rad-years at risk, and thus, from our computations, the internal risk coefficient for the Marshallese children was estimated to range between 1.0 and 1.4 cancers per million person-rad-years at risk. In contrast, for individual more than 10 years of age at the time of exposure, the dose from internal irradiation of the thyroid with short-lived internal emitters produced several times more thyroid cancer than did the same dose of radiation given externally. The external risk coefficients for the older age groups were reported in the literature to be in the range of 1.0 to 3.3 cancers per million person-rad-years-at risk. We computed internal risk coefficients of 3.3 to 8.1 cancers per million person-rad-years at risk for adolescent and adult groups. This higher sensitivity to cancer induction in the exposed adolescents and adults, is different from that seen in other exposed groups. 14 refs., 8 tabs.

  2. A short guide to exponential Krylov subspace time integration for Maxwell's equations

    NARCIS (Netherlands)

    Botchev, Mike A.

    2012-01-01

    The exponential time integration, i.e., time integration which involves the matrix exponential, is an attractive tool for solving Maxwell's equations in time. However, its application in practice often requires a substantial knowledge of numerical linear algebra algorithms, in particular, of the Kry

  3. Integrating random matrix theory predictions with short-time dynamical effects in chaotic systems.

    Science.gov (United States)

    Smith, A Matthew; Kaplan, Lev

    2010-07-01

    We discuss a modification to random matrix theory eigenstate statistics that systematically takes into account the nonuniversal short-time behavior of chaotic systems. The method avoids diagonalization of the Hamiltonian; instead it requires only knowledge of short-time dynamics for a chaotic system or ensemble of similar systems. Standard random matrix theory and semiclassical predictions are recovered in the limits of zero Ehrenfest time and infinite Heisenberg time, respectively. As examples, we discuss wave-function autocorrelations and cross correlations, and show that significant improvement in accuracy is obtained for simple chaotic systems where comparison can be made with brute-force diagonalization. The accuracy of the method persists even when the short-time dynamics of the system or ensemble is known only in a classical approximation. Further improvement in the rate of convergence is obtained when the method is combined with the correlation function bootstrapping approach introduced previously.

  4. Using Short Texts to Teach English as Second Language: An Integrated Approach

    Science.gov (United States)

    Kembo, Jane

    2016-01-01

    The teacher of English Language is often hard pressed to find interesting and authentic ways to present language to target second language speakers. While language can be taught and learned, part of it must be acquired and short texts provide powerful tools for doing so and reinforcing what has been taught/learned. This paper starts from research,…

  5. Effect of Vagus nerve integrity on short and long-term efficacy of antireflux surgery

    NARCIS (Netherlands)

    Van Rijn, S.; Rinsma, N. F.; Van Herwaarden-Lindeboom, M. Y A; Ringers, J.; Gooszen, H. G.; Van Rijn, P. J J; Veenendaal, R. A.; Conchillo, J. M.; Bouvy, N. D.; Masclee, Adrian A M

    2016-01-01

    OBJECTIVES:Vagus nerve injury is a feared complication of antireflux surgery (ARS) that may negatively affect reflux control. The aim of the present prospective study was to evaluate short-term and long-term impact of vagus nerve injury, evaluated by pancreatic polypeptide response to insulin-induce

  6. Integration of palliative medicine into comprehensive cancer care.

    Science.gov (United States)

    Lagman, Ruth; Walsh, Declan

    2005-04-01

    Because of the advent of disease-modifying agents for patients with malignancies, cancer is now a chronic illness. However, most cancer patients will experience significant symptoms and complications during the course of their illness or its treatment. In addition to their physical symptoms, patient and families are burdened with psychological, social, and spiritual difficulties. Palliative medicine addresses all these issues and complements attempts to cure the disease; it is an essential part of modern comprehensive cancer care.

  7. Non-thyroid cancer in Northern Ukraine in the post-Chernobyl period: Short report.

    Science.gov (United States)

    Hatch, M; Ostroumova, E; Brenner, A; Federenko, Z; Gorokh, Y; Zvinchuk, O; Shpak, V; Tereschenko, V; Tronko, M; Mabuchi, K

    2015-06-01

    The Chernobyl nuclear power plant accident in Ukraine in 1986 led to widespread radioactive releases into the environment - primarily of radioiodines and cesium - heavily affecting the northern portions of the country, with settlement-averaged thyroid doses estimated to range from 10 mGy to more than 10 Gy. The increased risk of thyroid cancer among exposed children and adolescents is well established but the impact of radioactive contamination on the risk of other types of cancer is much less certain. To provide data on a public health issue of major importance, we have analyzed the incidence of non-thyroid cancers during the post-Chernobyl period in a well-defined cohort of 13,203 individuals who were cancers identified through linkage with the National Cancer Registry of Ukraine for the period 1998 through 2009. We compared the observed and expected number of cases in three cancer groupings: all solid cancers excluding thyroid, leukemia, and lymphoma. Our analyses found no evidence of a statistically significant elevation in cancer risks in this cohort exposed at radiosensitive ages, although the cancer trends, particularly for leukemia (SIR=1.92, 95% confidence interval: 0.69; 4.13), should continue to be monitored.

  8. Lymphoscintigraphy in breast cancer: a short review about the impact on upper limb after surgical treatment

    Directory of Open Access Journals (Sweden)

    Anke Bergmann

    2008-12-01

    Full Text Available Breast cancer is still associated with high mortality rates and one of the most important factors governing long survival is accurate and early diagnosis. In underdeveloped countries, this disease frequently is only detected in advanced stages; however, through mammography, many women have been diagnosed at early stages. In this context, the sentinel lymph node (SLN technique is associated with less postoperative morbidity compared to axillary lymphadenectomy. Lymphoscintigraphy has emerged as a method for the evaluation of lymphatic drainage chains in various tumours, being both accurate and non invasive. The aim of this work is to present the main aspects which cause controversy about SLN and lymphoscintigraphy and the impact that these procedures have had on lymphedema after surgical treatment for breast cancer. A short review including papers in English, Spanish and Portuguese, available on Lilacs and Medline database, published between January, 2000 and July, 2008 was performed. The key words breast cancer, lymphoscintigraphy, SLN biopsy, lymphedema were used. Various studies have aimed to compare the incidence and prevalence of lymphedema according to the technique used; however, the population subjected to SLN is different from the one with indication for axillary lymphadenectomy regarding staging. Moreover, little is known about long term morbidity since it is a relatively new technique. In conclusion, the development of surgical techniques has permitted to minimize deformities and the current trend is that these techniques be as conservative as possible. Thus, lymphoscintigraphy plays an important role in the identification of SLN, contributing to the prevention and minimization of postoperative complications.O câncer de mama é ainda associado com altas taxas de mortalidade e um dos mais importantes fatores de manutenção de longa sobrevivência é a precisão e o diagnóstico precoce. Em países em desenvolvimento, essa doença freq

  9. Integrating Multiple Microarray Data for Cancer Pathway Analysis Using Bootstrapping K-S Test

    Directory of Open Access Journals (Sweden)

    Bing Han

    2009-01-01

    Full Text Available Previous applications of microarray technology for cancer research have mostly focused on identifying genes that are differentially expressed between a particular cancer and normal cells. In a biological system, genes perform different molecular functions and regulate various biological processes via interactions with other genes thus forming a variety of complex networks. Therefore, it is critical to understand the relationship (e.g., interactions between genes across different types of cancer in order to gain insights into the molecular mechanisms of cancer. Here we propose an integrative method based on the bootstrapping Kolmogorov-Smirnov test and a large set of microarray data produced with various types of cancer to discover common molecular changes in cells from normal state to cancerous state. We evaluate our method using three key pathways related to cancer and demonstrate that it is capable of finding meaningful alterations in gene relations.

  10. The process of short- and long-term price integration in the Benin maize market.

    NARCIS (Netherlands)

    Lutz, C.; Tilburg, van A.; Kamp, van der B.J.

    1995-01-01

    This paper reviews the methodology used to study the price integration process in spatially separated spot markets, and applies it to the Benin maize market. An autoregressive distributed lag model is derived to take into account the sluggishness of price adjustments. Hypothesis testing concerns sta

  11. Short term Braking Capability during Power Interruptions for Integrated Matrix Converter-Motor Drives

    DEFF Research Database (Denmark)

    Klumpner, Christian; Blaabjerg, Frede

    2002-01-01

    The new trend in Adjustable Speed Drives (ASD) is to integrate the inverter and the motor into a single unit in order to reduce the production cost, the commissioning time and the physical size of the equipment. This last issue becomes more important, making the matrix converter topology more...

  12. Short term braking capability during power interruptions for integrated matrix converter

    DEFF Research Database (Denmark)

    Klumpner, Christian; Blaabjerg, Frede

    2004-01-01

    The new trend in adjustable speed drives (ASD) is to integrate the inverter and the motor into a single unit in order to reduce the production cost, the commissioning time, and the physical size of the equipment. This last issue becomes more important, making the matrix converter topology more...

  13. Role of Kampo Medicine in Integrative Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jun-ichi Yamakawa

    2013-01-01

    Full Text Available Clinical trials to date demonstrate that standard cancer treatments are currently the most efficient treatments for large numbers of cancer patients. Cancer treatments will increasingly require approaches that allow patients to live with cancer, by increasing their natural healing power and tumor immunity, as well as attenuating the progression of their cancers, instead of only attacking the cancer cells directly. Complementary and alternative medicine, including Kampo medicine, compensates for the drawbacks of western medicine by increasing patients’ self-defense mechanisms. In Japan, clinicians who have studied both western medicine and Kampo treat cancer patients by fusing the two medical systems into a unitary one. The goal of the system is to assist the functional maintenance and recovery of the living body complex with the physical, mental, social, and spiritual balance, rather than addressing direct antitumor effects. In this review, we describe the usefulness of Kampo medicine, especially juzentaihoto, and outline the reports on evidence, in addition to the report on an attitudinal survey about the use of Kampo medicine in cancer treatment in Japan.

  14. Integrated profiling of basal and luminal breast cancers.

    NARCIS (Netherlands)

    Adelaide, J.; Finetti, P.; Bekhouche, I.; Repellini, L.; Geneix, J.; Sircoulomb, F.; Charafe-Jauffret, E.; Cervera, N.; Desplans, J.; Parzy, D.; Schoenmakers, E.F.P.M.; Viens, P.; Jacquemier, J.; Birnbaum, D.; Bertucci, F.; Chaffanet, M.

    2007-01-01

    Basal and luminal are two molecular subtypes of breast cancer with opposite histoclinical features. We report a combined, high-resolution analysis of genome copy number and gene expression in primary basal and luminal breast cancers. First, we identified and compared genomic alterations in 45 basal

  15. Comparison of perioperative and short-term outcomes between robotic and conventional laparoscopic surgery for colonic cancer: a systematic review and meta-analysis

    Science.gov (United States)

    Lim, Sungwon; Kim, Jin Hee; Baek, Se-Jin; Kim, Seon-Hahn

    2016-01-01

    Purpose Reports from several case series have described the feasibility and safety of robotic surgery (RS) for colonic cancer. Experience is still limited in robotic colonic surgery, and a few meta-analysis has been conducted to integrate the results for colon cancer specifically. We conducted a systematic review of the available evidence comparing the surgical safety and efficacy of RS with that of conventional laparoscopic surgery (CLS) for colonic cancer. Methods We searched English databases (MEDLINE, Embase, and Cochrane Library), and Korean databases (KoreaMed, KMbase, KISS, RISS, and KisTi). Dichotomous variables were pooled using the risk ratio, and continuous variables were pooled using the mean difference (MD). Results The present study found that the RS group had a shorter time to resumption of a regular diet (MD, –0.62 days; 95% CI, –0.97 to –0.28), first passage of flatus (MD, –0.44 days; 95% CI, –0.66 to –0.23) and defecation (MD, –0.62 days; 95% CI, –0.77 to –0.47). Also, RS was associated with a shorter hospital stay (MD, –0.69 days; 95% CI, –1.12 to –0.26), a lower estimated blood loss (MD, –19.49 mL; 95% CI, –27.10 to –11.89) and a longer proximal margin (MD, 2.29 cm; 95% CI, 1.11-3.47). However, RS was associated with a longer surgery time (MD, 51.00 minutes; 95% CI, 39.38–62.62). Conclusion We found that the potential benefits of perioperative and short-term outcomes for RS than for CLS. For a more accurate understanding of RS for colonic cancer patients, robust comparative studies and randomized clinical trials are required. PMID:27274509

  16. A short history of stochastic integration and mathematical finance: the early years, 1880–1970

    OpenAIRE

    Jarrow, Robert; Protter, Philip

    2004-01-01

    We present a history of the development of the theory of Stochastic Integration, starting from its roots with Brownian motion, up to the introduction of semimartingales and the independence of the theory from an underlying Markov process framework. We show how the development has influenced and in turn been influenced by the development of Mathematical Finance Theory. The calendar period is from 1880 to 1970.

  17. Efficacy of psychodynamic short-term psychotherapy for depressed breast cancer patients: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Zwerenz Rüdiger

    2012-12-01

    Full Text Available Abstract Background There is a lack of psychotherapeutic trials of treatments of comorbid depression in cancer patients. Our study determines the efficacy of a manualized short-term psychodynamic psychotherapy and predictors of outcome by personality and quality of the therapeutic relationship. Methods/design Eligible breast cancer patients with comorbid depression are assigned to short-term psychodynamic psychotherapy (up to 20 + 5 sessions or to treatment as usual (augmented by recommendation for counseling center and physician information. We plan to recruit a total of 180 patients (90 per arm in two centers. Assessments are conducted pretreatment, after 6 (treatment termination and 12 months (follow-up. The primary outcome measures are reduction of the depression score in the Hospital Anxiety and Depression Scale and remission of depression as assessed by means of the Structured Clinical Interview for DSM IV Disorders by independent, blinded assessors at treatment termination. Secondary outcomes refer to quality of life. Discussion We investigate the efficacy of short-term psychodynamic psychotherapy in acute care and we aim to identify predictors for acceptance and success of treatment. Trial registration ISRCTN96793588

  18. Evaluation and integration of cancer gene classifiers: identification and ranking of plausible drivers.

    Science.gov (United States)

    Liu, Yang; Tian, Feng; Hu, Zhenjun; DeLisi, Charles

    2015-05-11

    The number of mutated genes in cancer cells is far larger than the number of mutations that drive cancer. The difficulty this creates for identifying relevant alterations has stimulated the development of various computational approaches to distinguishing drivers from bystanders. We develop and apply an ensemble classifier (EC) machine learning method, which integrates 10 classifiers that are publically available, and apply it to breast and ovarian cancer. In particular we find the following: (1) Using both standard and non-standard metrics, EC almost always outperforms single method classifiers, often by wide margins. (2) Of the 50 highest ranked genes for breast (ovarian) cancer, 34 (30) are associated with other cancers in either the OMIM, CGC or NCG database (P plausible. Biological implications are briefly discussed. Source codes and detailed results are available at http://www.visantnet.org/misi/driver_integration.zip.

  19. Gastric Cancer Associated Genes Identified by an Integrative Analysis of Gene Expression Data

    Science.gov (United States)

    Jiang, Bing; Li, Shuwen; Jiang, Zhi

    2017-01-01

    Gastric cancer is one of the most severe complex diseases with high morbidity and mortality in the world. The molecular mechanisms and risk factors for this disease are still not clear since the cancer heterogeneity caused by different genetic and environmental factors. With more and more expression data accumulated nowadays, we can perform integrative analysis for these data to understand the complexity of gastric cancer and to identify consensus players for the heterogeneous cancer. In the present work, we screened the published gene expression data and analyzed them with integrative tool, combined with pathway and gene ontology enrichment investigation. We identified several consensus differentially expressed genes and these genes were further confirmed with literature mining; at last, two genes, that is, immunoglobulin J chain and C-X-C motif chemokine ligand 17, were screened as novel gastric cancer associated genes. Experimental validation is proposed to further confirm this finding. PMID:28232943

  20. Diet Quality Index as a predictor of short-term mortality in the American Cancer Society Cancer Prevention Study II Nutrition Cohort.

    Science.gov (United States)

    Seymour, Jennifer D; Calle, Eugenia E; Flagg, Elaine W; Coates, Ralph J; Ford, Earl S; Thun, Michael J

    2003-06-01

    The Diet Quality Index (DQI) was developed to measure overall dietary patterns and to predict chronic disease risk. This study examined associations between DQI and short-term all-cause, all-circulatory-disease, and all-cancer mortality in the American Cancer Society Cancer Prevention Study II Nutrition Cohort, a cohort of US adults aged 50-79 years enrolled in a prospective study. After 4 years of follow-up (1992-1996), there were 869 deaths among 63,109 women and 1,736 deaths among 52,724 men. All study participants reported being disease free at baseline in 1992-1993. In age-adjusted Cox models, a higher DQI, which was indicative of a poorer quality diet, was positively related to all-cause and all-circulatory-disease mortality rates in both women and men and to cancer mortality in men only. However, in fully adjusted Cox models, only circulatory disease mortality was clearly positively related to DQI and only in women (medium-low-quality diet vs. highest-quality diet: rate ratio = 1.86, 95% confidence interval: 1.19, 2.89). Although trend tests indicated significant positive relations between DQI and all-cause mortality, effects were small (rate ratios cancer mortality. As currently constructed, the DQI may have limited ability to predict mortality.

  1. Integrating complementary and alternative medicine into cancer care: Canadian oncology nurses′ perspectives

    Directory of Open Access Journals (Sweden)

    Tracy L Truant

    2015-01-01

    Full Text Available The integration of complementary and alternative medicine (CAM and conventional cancer care in Canada is in its nascent stages. While most patients use CAM during their cancer experience, the majority does not receive adequate support from their oncology health care professionals (HCPs to integrate CAM safely and effectively into their treatment and care. A variety of factors influence this lack of integration in Canada, such as health care professional(HCP education and attitudes about CAM; variable licensure, credentialing of CAM practitioners, and reimbursement issues across the country; an emerging CAM evidence base; and models of cancer care that privilege diseased-focused care at the expense of whole person care. Oncology nurses are optimally aligned to be leaders in the integration of CAM into cancer care in Canada. Beyond the respect afforded to oncology nurses by patients and family members that support them in broaching the topic of CAM, policies, and position statements exist that allow oncology nurses to include CAM as part of their scope. Oncology nurses have also taken on leadership roles in clinical innovation, research, education, and advocacy that are integral to the safe and informed integration of evidence-based CAM therapies into cancer care settings in Canada.

  2. Muscle Adaptations Following Short-Duration Bed Rest with Integrated Resistance, Interval, and Aerobic Exercise

    Science.gov (United States)

    Hackney, Kyle J.; Scott, Jessica M.; Buxton, Roxanne; Redd-Goetchius, Elizabeth; Crowell, J. Brent; Everett, Meghan E.; Wickwire, Jason; Ryder, Jeffrey W.; Bloomberg, Jacob J.; Ploutz-Snyder, Lori L.

    2011-01-01

    Unloading of the musculoskeletal system during space flight results in deconditioning that may impair mission-related task performance in astronauts. Exercise countermeasures have been frequently tested during bed rest (BR) and limb suspension; however, high-intensity, short-duration exercise prescriptions have not been fully explored. PURPOSE: To determine if a high intensity resistance, interval, and aerobic exercise program could protect against muscle atrophy and dysfunction when performed during short duration BR. METHODS: Nine subjects (1 female, 8 male) performed a combination of supine exercises during 2 weeks of horizontal BR. Resistance exercise (3 d / wk) consisted of squat, leg press, hamstring curl, and heel raise exercises (3 sets, 12 repetitions). Aerobic (6 d / wk) sessions alternated continuous (75% VO2 peak) and interval exercise (30 s, 2 min, and 4 min) and were completed on a supine cycle ergometer and vertical treadmill, respectively. Muscle volumes of the upper leg were calculated pre, mid, and post-BR using magnetic resonance imaging. Maximal isometric force (MIF), rate of force development (RFD), and peak power of the lower body extensors were measured twice before BR (averaged to represent pre) and once post BR. ANOVA with repeated measures and a priori planned contrasts were used to test for differences. RESULTS: There were no changes to quadriceps, hamstring, and adductor muscle volumes at mid and post BR time points compared to pre BR (Table 1). Peak power increased significantly from 1614 +/- 372 W to 1739 +/- 359 W post BR (+7.7%, p = 0.035). Neither MIF (pre: 1676 +/- 320 N vs. post: 1711 +/- 250 N, +2.1%, p = 0.333) nor RFD (pre: 7534 +/- 1265 N/ms vs. post: 6951 +/- 1241 N/ms, -7.7%, p = 0.136) were significantly impaired post BR.

  3. Short-term retention of relational memory in amnesia revisited: accurate performance depends on hippocampal integrity.

    Science.gov (United States)

    Yee, Lydia T S; Hannula, Deborah E; Tranel, Daniel; Cohen, Neal J

    2014-01-01

    Traditionally, it has been proposed that the hippocampus and adjacent medial temporal lobe cortical structures are selectively critical for long-term declarative memory, which entails memory for inter-item and item-context relationships. Whether the hippocampus might also contribute to short-term retention of relational memory representations has remained controversial. In two experiments, we revisit this question by testing memory for relationships among items embedded in scenes using a standard working memory trial structure in which a sample stimulus is followed by a brief delay and the corresponding test stimulus. In each experimental block, eight trials using different exemplars of the same scene were presented. The exemplars contained the same items but with different spatial relationships among them. By repeating the pictures across trials, any potential contributions of item or scene memory to performance were minimized, and relational memory could be assessed more directly than has been done previously. When test displays were presented, participants indicated whether any of the item-location relationships had changed. Then, regardless of their responses (and whether any item did change its location), participants indicated on a forced-choice test, which item might have moved, guessing if necessary. Amnesic patients were impaired on the change detection test, and were frequently unable to specify the change after having reported correctly that a change had taken place. Comparison participants, by contrast, frequently identified the change even when they failed to report the mismatch, an outcome that speaks to the sensitivity of the change specification measure. These results confirm past reports of hippocampal contributions to short-term retention of relational memory representations, and suggest that the role of the hippocampus in memory has more to do with relational memory requirements than the length of a retention interval.

  4. Short-term Retention of Relational Memory in Amnesia Revisited: Accurate Performance Depends on Hippocampal Integrity

    Directory of Open Access Journals (Sweden)

    Lydia T.S. Yee

    2014-01-01

    Full Text Available Traditionally, it has been proposed that the hippocampus and adjacent medial temporal lobe cortical structures are selectively critical for long-term declarative memory, which entails memory for inter-item and item-context relationships. Whether the hippocampus might also contribute to short-term retention of relational memory representations has remained controversial. In two experiments, we revisit this question by testing memory for relationships among items embedded in scenes using a standard working memory trial structure in which a sample stimulus is followed by a brief delay and the corresponding test stimulus. In each experimental block, eight trials using different exemplars of the same scene were presented. The exemplars contained the same items but with different spatial relationships among them. By repeating the pictures across trials, any potential contributions of item or scene memory to performance were minimized, and relational memory could be assessed more directly than has been done previously. When test displays were presented, participants indicated whether any of the item-location relationships had changed. Then, regardless of their responses (and whether any item did change its location, participants indicated on a forced-choice test, which item might have moved, guessing if necessary. Amnesic patients were impaired on the change detection test, and were frequently unable to specify the change after having reported correctly that a change had taken place. Comparison participants, by contrast, frequently identified the change even when they failed to report the mismatch, an outcome that speaks to the sensitivity of the change specification measure. These results confirm past reports of hippocampal contributions to short-term retention of relational memory representations, and suggest that the role of the hippocampus in memory has more to do with relational memory requirements than the length of a retention interval.

  5. IDICAP: A Novel Tool for Integrating Drug Intervention Based on Cancer Panel

    Directory of Open Access Journals (Sweden)

    Noelle Kosarek

    2016-10-01

    Full Text Available Cancer is a heterogeneous disease afflicting millions of people of all ages and their families worldwide. Tremendous resources have been and continue to be devoted to the development of cancer treatments that target the unique mutation profiles of patients, namely targeted cancer therapy. However, the sheer volume of drugs coupled with cancer heterogeneity becomes a challenge for physicians to prescribe effective therapies targeting patients’ unique genetic mutations. Developing a web service that allows clinicians as well as patients to identify effective drug therapies, both approved and experimental, would be helpful for both parties. We have developed an innovative web service, IDICAP, which stands for Integrated Drug Intervention for CAncer Panel. It uses genes that have been linked to a cancer type to search for drug and clinical trial information from ClinicalTrials.gov and DrugBank. IDICAP selects and integrates information pertaining to clinical trials, disease conditions, drugs under trial, locations of trials, drugs that are known to target the queried gene, and any known single nucleotide polymorphism (SNP effects. We tested IDICAP by gene panels that contribute to breast cancer, ovarian cancer, and cancer in general. Clinical trials and drugs listed by our tool showed improved precision compared to the results from ClinicalTrials.gov and Drug Gene Interaction Database (DGIdb. Furthermore, IDICAP provides patients and doctors with a list of clinical facilities in their proximity, a characteristic that lends credence to the Precision Medicine Initiative launched by the White House in the United States in 2015.

  6. Integrated modelling framework for short pulse high energy density physics experiments

    Science.gov (United States)

    Sircombe, N. J.; Hughes, S. J.; Ramsay, M. G.

    2016-03-01

    Modelling experimental campaigns on the Orion laser at AWE, and developing a viable point-design for fast ignition (FI), calls for a multi-scale approach; a complete description of the problem would require an extensive range of physics which cannot realistically be included in a single code. For modelling the laser-plasma interaction (LPI) we need a fine mesh which can capture the dispersion of electromagnetic waves, and a kinetic model for each plasma species. In the dense material of the bulk target, away from the LPI region, collisional physics dominates. The transport of hot particles generated by the action of the laser is dependent on their slowing and stopping in the dense material and their need to draw a return current. These effects will heat the target, which in turn influences transport. On longer timescales, the hydrodynamic response of the target will begin to play a role as the pressure generated from isochoric heating begins to take effect. Recent effort at AWE [1] has focussed on the development of an integrated code suite based on: the particle in cell code EPOCH, to model LPI; the Monte-Carlo electron transport code THOR, to model the onward transport of hot electrons; and the radiation hydrodynamics code CORVUS, to model the hydrodynamic response of the target. We outline the methodology adopted, elucidate on the advantages of a robustly integrated code suite compared to a single code approach, demonstrate the integrated code suite's application to modelling the heating of buried layers on Orion, and assess the potential of such experiments for the validation of modelling capability in advance of more ambitious HEDP experiments, as a step towards a predictive modelling capability for FI.

  7. Stress, Metabolism and Cancer: Integrated Pathways Contributing to Immune Suppression

    OpenAIRE

    Repasky, Elizabeth A.; Eng, Jason; Hylander, Bonnie L

    2015-01-01

    The potential for immune cells to control cancers has been recognized for many decades, but only recently has real excitement begun to spread through the oncology community following clear evidence that therapeutic blockade of specific immune-suppressive mechanisms is enough to make a real difference in survival for patients with several different advanced cancers. However, impressive and encouraging as these new clinical data are, it is clear that more effort should be devoted toward underst...

  8. Conversion of laparoscopic colorectal resection for cancer: What is the impact on short-term outcomes and survival?

    Science.gov (United States)

    Allaix, Marco E; Furnée, Edgar J B; Mistrangelo, Massimiliano; Arezzo, Alberto; Morino, Mario

    2016-01-01

    and rectal cancer on both short-term outcomes and long-term survival. PMID:27729737

  9. MicroRNAs: short non-coding players in cancer chemoresistance.

    Science.gov (United States)

    Donzelli, Sara; Mori, Federica; Biagioni, Francesca; Bellissimo, Teresa; Pulito, Claudio; Muti, Paola; Strano, Sabrina; Blandino, Giovanni

    2014-01-01

    Chemoresistance is one of the main problems in the therapy of cancer. There are a number of different molecular mechanisms through which a cancer cell acquires resistance to a specific treatment, such as alterations in drug uptake, drug metabolism and drug targets. There are several lines of evidence showing that miRNAs are involved in drug sensitivity of cancer cells in different tumor types and by different treatments. In this review, we provide an overview of the more recent and significant findings on the role of miRNAs in cancer cell drug resistance. In particular, we focus on specific miRNA mechanisms of action that in various steps lead from drug cell sensitivity to drug cell resistance. We also provide evidence on how miRNA profiling may unveil relevant predictive biomarkers for therapy outcomes.

  10. Non-thyroid cancer in Northern Ukraine in the post-Chernobyl period: Short Report

    OpenAIRE

    Hatch, M.; Ostroumova, E.; Brenner, A.; Federenko, Z; Gorokh, Y; Zvinchuk, O; Shpak, V.; Tereschenko, V.; Tronko, M.; Mabuchi, K

    2015-01-01

    The Chernobyl nuclear power plant accident in Ukraine in 1986 led to widespread radioactive releases into the environment - primarily of radioiodines and cesium – heavily affecting the northern portions of the country, with settlement-averaged thyroid doses estimated to range from 10 mGy to more than 10 Gy. The increased risk of thyroid cancer among exposed children and adolescents is well-established but the impact of radioactive contamination on the risk of other types of cancer is much les...

  11. Metformin for cancer and aging prevention: is it a time to make the long story short?

    OpenAIRE

    2015-01-01

    During the last decade, the burst of interest is observed to antidiabetic biguanide metformin as candidate drug for cancer chemoprevention. The analysis of the available data have shown that the efficacy of cancer preventive effect of metformin (MF) and another biguanides, buformin (BF) and phenformin (PF), has been studied in relation to total tumor incidence and to 17 target organs, in 21 various strains of mice, 4 strains of rats and 1 strain of hamsters (inbred, outbred, transgenic, mutan...

  12. Long-term and short-term effects of insomnia in cancer and effective interventions.

    Science.gov (United States)

    Davis, Mellar P; Goforth, Harold W

    2014-01-01

    Sleep disorders and insomnia are more prevalent in patients with cancer than in the normal population. Sleep disorders consist of delayed sleep latency, waking episodes after sleep onset, unrefreshing sleep, reduced quality of sleep, and reduced sleep efficiency. Sleep disorders cluster with pain, fatigue, depression, anxiety, and vasomotor symptoms, depending on stage of disease, treatment, and comorbidities. Premorbid sleep problems and shift work have been associated with a higher prevalence of cancer; in fact, shift work has been labeled a carcinogen. Treatment for insomnia includes cognitive behavioral therapy with sleep hygiene, bright-light therapy, exercise, yoga, melatonin, and hypnotic medications. Unfortunately, there are few randomized trials in cancer-related sleep disorders such that most recommendations particularly for hypnotics are based on treatment for primary insomnia. In this article, insomnia is reviewed as a predisposing factor to cancer, prior to and during treatment, in cancer survivorship and in advanced cancer. Recommendations for treatment are based on low-quality evidence but are also reviewed.

  13. Compact Shorted Stacked-Patch Antenna Integrated with Chip-Package Based on LTCC Technology

    Directory of Open Access Journals (Sweden)

    Yongjiu Li

    2014-01-01

    Full Text Available A low profile chip-package stacked-patch antenna is proposed by using low temperature cofired ceramic (LTCC technology. The proposed antenna employs a stacked-patch to achieve two operating frequency bands and enhance the bandwidth. The height of the antenna is decreased to 4.09 mm (about λ/25 at 2.45 GHz due to the shorted pin. The package is mounted on a 44 × 44 mm2 ground plane to miniaturize the volume of the system. The design parameters of the antenna and the effect of the antenna on chip-package cavity are carefully analyzed. The designed antenna operates at a center frequency of 2.45 GHz and its impedance bandwidth (S11< -10 dB is 200 MHz, resulting from two neighboring resonant frequencies at 2.41 and 2.51 GHz, respectively. The average gain across the frequency band is about 5.28 dBi.

  14. Identification of ovarian cancer associated genes using an integrated approach in a Boolean framework

    Science.gov (United States)

    2013-01-01

    Background Cancer is a complex disease where molecular mechanism remains elusive. A systems approach is needed to integrate diverse biological information for the prognosis and therapy risk assessment using mechanistic approach to understand gene interactions in pathways and networks and functional attributes to unravel the biological behaviour of tumors. Results We weighted the functional attributes based on various functional properties observed between cancerous and non-cancerous genes reported from literature. This weighing schema was then encoded in a Boolean logic framework to rank differentially expressed genes. We have identified 17 genes to be differentially expressed from a total of 11,173 genes, where ten genes are reported to be down-regulated via epigenetic inactivation and seven genes are up-regulated. Here, we report that the overexpressed genes IRAK1, CHEK1 and BUB1 may play an important role in ovarian cancer. We also show that these 17 genes can be used to form an ovarian cancer signature, to distinguish normal from ovarian cancer subjects and that the set of three genes, CHEK1, AR, and LYN, can be used to classify good and poor prognostic tumors. Conclusion We provided a workflow using a Boolean logic schema for the identification of differentially expressed genes by integrating diverse biological information. This integrated approach resulted in the identification of genes as potential biomarkers in ovarian cancer. PMID:23383610

  15. Complementary Therapy for Cancer Survivors: Integrative Nursing Care

    Directory of Open Access Journals (Sweden)

    Kazuko Onishi

    2016-01-01

    Full Text Available Objective: The number of cancer patients who survive more than 5 years after the completion of their initial treatment is increasing. Oncology nurses must consider the needs of long-term cancer survivors in addition to those of cancer patients undergoing treatment because cancer survivors experience anxiety over several issues, including the risk of recurrence and progression of cancer status and symptom management. Methods: We tried to examine the effect of complementary therapy (CT to reduce anxiety. The experimental study compared an intervention group (5 males and 68 females that underwent four CTs and a control group (5 males and 56 females that received no intervention. The intervention group practiced the CTs in their home for 20 min/day, 2 days/week, for 8 weeks, for a total of 16 times, whereas the control group performed their usual routines. Stress response scale-18 (SRS-18 scores consisting of three subscales (depression-anxiety, temper-anger, and lethargy were compared between the groups and across time within each group. Results: The intervention group reduced depression and anxiety significantly than the control group. Furthermore, the intervention group expressed the following positive feedback: "being able to relax," "being distracted from their worries and anxieties," "being able to sleep," "feeling more in-touch with reality," and "wanting to continue the practice." Conclusions: The study might accurately reflect the perspectives of women with cancer because the majority of the patients were women. Meanwhile, the result suggests that CTs might be useful for long-term cancer survivors who experience anxiety that influence their quality of life.

  16. Integrative oncology for breast cancer patients: introduction of an expert-based model

    Directory of Open Access Journals (Sweden)

    Dobos Gustav J

    2012-11-01

    Full Text Available Abstract Background Malignant breast neoplasms are among the most frequent forms of cancer in the Western world. Conventional treatment of breast cancer may include surgery, hormonal therapy, chemotherapy, radiation and/or immunotherapy, all of which are often accompanied by severe side effects. Complementary and alternative medicine (CAM treatments have been shown to be effective in alleviating those symptoms. Furthermore, with patient survival rates increasing, oncologists, psychologists and other therapists have to become more sensitive to the needs of cancer survivors that go beyond than the mere alleviation of symptoms. Many CAM methods are geared to treat the patient in a holistic manner and thus are also concerned with the patient’s psychological and spiritual needs. Discussion The use of certain CAM methods may become problematic when, as frequently occurs, patients use them indiscriminately and without informing their oncologists. Herbal medicines and dietary supplements, especially, may interfere with primary cancer treatments or have other detrimental effects. Thus, expertise in this highly specialized field of integrative medicine should be available to patients so that they can be advised about the benefits and negative effects of such preparations and practices. Being a beneficial combination of conventional and CAM care, integrative oncology makes possible the holistic approach to cancer care. The concept of integrative oncology for breast cancer is jointly practiced by the Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, academic teaching hospital of the University of Duisburg-Essen, and the Breast Center at Kliniken Essen-Mitte in Germany. This model is introduced here; its scope is reviewed, and its possible implications for the practice of integrative medicine are discussed. Summary Evidence-based integrative care is crucial to the field of oncology in establishing state-of-the-art care for breast

  17. The short-term effects of an integrated care model for the frail elderly on health, quality of life, health care use and satisfaction with care

    NARCIS (Netherlands)

    W.M. Looman (Willemijn); I.N. Fabbricotti (Isabelle); R. Huijsman (Robbert)

    2014-01-01

    markdownabstract__Abstract__ Purpose: This study explores the short-term value of integrated care for the frail elderly by evaluating the effects of the Walcheren Integrated Care Model on health, quality of life, health care use and satisfaction with care after three months. Intervention: Frailty w

  18. Stress, metabolism and cancer: integrated pathways contributing to immune suppression.

    Science.gov (United States)

    Repasky, Elizabeth A; Eng, Jason; Hylander, Bonnie L

    2015-01-01

    The potential for immune cells to control cancers has been recognized for many decades, but only recently has real excitement begun to spread through the oncology community following clear evidence that therapeutic blockade of specific immune-suppressive mechanisms is enough to make a real difference in survival for patients with several different advanced cancers. However, impressive and encouraging as these new clinical data are, it is clear that more effort should be devoted toward understanding the full spectrum of factors within cancer patients, which have the potential to block or weaken antitumor activity by immune cells. The goal of this brief review is to highlight recent literature revealing interactive stress and metabolic pathways, particularly those mediated by the sympathetic nervous system, which may conspire to block immune cells from unleashing their full killing potential. There is exciting new information regarding the role of neurogenesis by tumors and adrenergic signaling in cancer progression (including metabolic changes associated with cachexia and lipolysis) and in regulation of immune cell function and differentiation. However, much more work is needed to fully understand how the systemic metabolic effects mediated by the brain and nervous system can be targeted for therapeutic efficacy in the setting of immunotherapy and other cancer therapies.

  19. An integrated, population-based framework for knowledge management for cancer control.

    Science.gov (United States)

    Hagen, Neil A; Craighead, Peter; Esmail, Rosmin

    2010-01-01

    Cancer control organizations commonly refer to the critical role of clinical practice guidelines to support the best possible cancer care. But how can a cancer care program ensure the systematic implementation of those guidelines? The goals of this article are to describe the process of developing a cancer control system driven by knowledge management, to highlight the key elements of this system and to foster discussion on the implementation of such frameworks. In order to promote best cancer practices within an expanded radiation service model for the province of Alberta, we developed an integrated conceptual framework for knowledge management. We identified six key elements of a knowledge management framework for the cancer program: evidence-based provincial guidelines, funding decisions, harmonized care pathways, targeted knowledge transfer projects, performance measurement and feedback to the system. We are establishing a process to characterize the explicit linkages and accountabilities between each of these elements as part of a broader cancer care quality agenda. We will implement the framework to support the start-up of the first of three new radiation treatment services in the province. The basic elements of a guidelines-supported cancer care system are not in doubt; how to unambiguously engage them within an integrated care system remains an area of intense interest.

  20. Complementary and integrative medicine for breast cancer patients - Evidence based practical recommendations.

    Science.gov (United States)

    Witt, C M; Cardoso, M J

    2016-08-01

    On average half of the breast cancer patients' population uses complementary and integrative medicine (CIM) therapies and many of them would like to receive information on CIM from their conventional treatment team. However, often they don't feel comfortable in discussing CIM related questions, with their conventional treatment team, because they think they don't have enough expertise and available time to deal with this topic. Furthermore, information on the evidence of CIM is not easily accessible and the available information is not always reliable. The purpose of the current paper is to provide: 1) an overview about the CIM interventions that have shown positive effects in breast cancer patients and might be useful in supportive cancer care, 2) practical guidance on how to choose and find a qualified referral to a CIM treatment: 3) recommendations on how these interventions could be integrated into Breast Cancer Centers and which factors should be taken into consideration in this setting. This paper takes available CIM practice guidelines for cancer patients and previous research on CIM implementation models into account. There are CIM interventions that have shown a potential to reduce symptoms of cancer or cancer treatments in breast cancer patients and the vast majority uses a non-pharmacological approach and have a good potential for implementation. Nevertheless, further and more rigorous research is still needed.

  1. Add-On Complementary Medicine in Cancer Care: Evidence in Literature and Experiences of Integration

    Directory of Open Access Journals (Sweden)

    Elio Rossi

    2017-01-01

    Full Text Available Background: According to the literature an increasing number of cancer patients demand for complementary therapies during their disease. Research has demonstrated that some of these therapies are effective and safe as adjunctive treatments in specific symptoms of these patients. Methods: The aims of the paper are to review the main and recent papers of international literature on the effectiveness of complementary medicine (CM therapies on side effects of anti-cancer protocols and improvement in the quality of life of oncological patients, and to describe the integration of evidence-based acupuncture, herbal medicine and homeopathy treatments in Public Cancer Network of the region of Tuscany. Results: After the review of literature and the approval of a Regional Resolution, some CM will be introduced in Cancer Departments in Tuscany to additionally treat cancer-related symptoms and side effects of conventional cancer therapy: acupuncture for nausea and post-chemotherapy and post-surgery vomiting, pain, hot flashes of iatrogenic menopause, xerostomia; homeopathy for hot flashes of iatrogenic menopause and the side effects of radiotherapy; herbal medicine for cancer-related fatigue, nausea and vomiting, pain, mucositis, anxiety, and depression. Conclusions: The integration of evidence-based complementary treatments allows for an effective response to the demand coming from cancer patients and combines safety and equity of access in public health systems.

  2. Apoptosis induced by short hairpin RNA-mediated STAT6 gene silencing in human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ming-sheng; ZHOU Yun-feng; ZHANG Wen-jie; ZHANG Xiao-lian; PAN Qin; JI Xue-mei; LUO Zhi-guo; WU Jian-ping

    2006-01-01

    Background The relationship between signal transduction and tumors has become one of the foci in cancer research. Signal transducer and activator of the transcription 6 (STAT6) signaling pathway is found to be activated in some cancer cells. But the function of the pathway in cancer cells is unknown. This study was undertaken to investigate the effect of the Stat6 signaling pathway on apoptosis in human colon cancer cells (HT-29 cells) and the possible mechanism of Stat6 by RNA interference techniques.Methods Four eukaryotic expression plasmid vectors of short hairpin RNA (shRNA) specific for the STAT6gene were designed and generated by molecular biological technology. The plasmid vectors were transfected into HT-29 cells by cation liposomes to block the Stat6 signaling pathway. The expressions of STAT6 mRNA and phosph-Stat6 protein were detected by the reverse transcriptase polymerase chain reaction (RT-PCR) method and flow cytometry respectively to screen the most effective shRNA at 72 hours after transfection. The apoptosis condition of the cells in which the expression of the STAT6 gene had been interfered was analyzed by flow cytometry and confocal microscopy. Both mRNA and protein expression of B cell lymphoma-2 (Bcl-2) and Bax were detected by RT-PCR and western blotting.Results Two effective eukaryotic expression plasmid vectors of shRNA specific for the STAT6 gene were generated successfully. One can reduce the expression of the STAT6 gene by 82.4% and the other by 56.8%(P<0.01). The apoptotic rate of colon cancer cells in which STAT6 gene expression had been interfered was significantly higher than that in controlled colon cancer cells (P<0.01). In the cells in which the Stat6 signaling pathway was blocked, the levels of mRNA and protein Bcl-2 were significantly decreased, whereas those of Bax were significantly increased (P<0.01).Conclusions The Stat6 signaling pathway can inhibit apoptosis in human colon cancer cells. The subsequent disorder of

  3. Quality of life in cancer survivors: an integrative review

    Directory of Open Access Journals (Sweden)

    Bruna Knob Pinto

    2013-09-01

    Full Text Available This study aims at identifying factors related to the quality of life of cancer survivors. The databases PubMed, LILACS and SciELO were used, being quality of life, survival and neoplasms the main keywords entered. Sixty-eight articles were found and ten that approached aspects related to quality of life of cancer survivors were selected. The results analysis was performed in stages. Several factors were identified and grouped into physical (chewing, pain and others, psychological (disease conception, social, financial (high cost of treatment and miscellaneous (age, treatment performance among others. It is believed that the analysis of the different areas that comprise the quality of life of patients can assist health professionals in the implementation of assistance practices that consider the multidimensionality of cancer survival.

  4. A short-term psychoeducational intervention for patients newly diagnosed with cancer.

    Science.gov (United States)

    Fawzy, F I

    1995-07-01

    The psychological and medical problems encountered by cancer patients are numerous and unique. The diagnosis of cancer frequently produces psychological distress. A review of the literature and the authors' clinical and research experience suggest that cancer patients may benefit from a variety of psychological intervention programs. A structured, psychiatric intervention consisting of health education, stress management/behavioral training, coping (including problem-solving techniques), and psychosocial group support offers the greatest potential benefit for patients newly diagnosed or in the early stages of their treatment. Early-stage interventions that encourage active behavioral coping and active cognitive coping rather than avoidance or passive acceptance of the illness can be helpful psychologically. These active behavioral and cognitive coping behaviors, which can be learned, can attenuate the psychological distress caused by stressful illness, decrease the amount of psychosocial adjustment to the illness needed, improve overall quality of life, and may also be associated with longer survival times.

  5. Patient empowerment in cancer pain management: an integrative literature review

    NARCIS (Netherlands)

    Boveldt, N.D. te; Vernooij-Dassen, M.; Leppink, I.; Samwel, H.; Vissers, K.; Engels, Y.M.

    2014-01-01

    OBJECTIVE: More than 50% of patients with cancer experience pain. Patient empowerment has been highlighted as central to success in pain management. Up to now, no clear model for this patient group exists, yet several strategies to empower patients have been used in clinical practice. This review ex

  6. Empowerment of cancer survivors through information technology: an integrative review

    NARCIS (Netherlands)

    Groen, W.G.; Kuijpers, W.; Oldenburg, H.S.A.; Wouters, M.W.J.M.; Aaronson, N.K.; van Harten, W.H.

    2015-01-01

    Background: Patient empowerment may be an effective approach to strengthen the role of cancer survivors and to reduce the burden on health care. However, it is not well conceptualized, notably in oncology. Furthermore, it is unclear to what extent information technology (IT) services can contribute

  7. Empowerment of Cancer Survivors Through Information Technology: An Integrative Review

    NARCIS (Netherlands)

    Groen, Wim G.; Kuijpers, Wilma; Oldenburg, Hester S.A.; Wouters, Michel W.J.M.; Aaronson, Neil K.; Harten, van Wim H.

    2015-01-01

    Background: Patient empowerment may be an effective approach to strengthen the role of cancer survivors and to reduce the burden on health care. However, it is not well conceptualized, notably in oncology. Furthermore, it is unclear to what extent information technology (IT) services can contribute

  8. Cancer

    Science.gov (United States)

    ... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...

  9. ProKinO: an ontology for integrative analysis of protein kinases in cancer.

    Directory of Open Access Journals (Sweden)

    Gurinder Gosal

    Full Text Available BACKGROUND: Protein kinases are a large and diverse family of enzymes that are genomically altered in many human cancers. Targeted cancer genome sequencing efforts have unveiled the mutational profiles of protein kinase genes from many different cancer types. While mutational data on protein kinases is currently catalogued in various databases, integration of mutation data with other forms of data on protein kinases such as sequence, structure, function and pathway is necessary to identify and characterize key cancer causing mutations. Integrative analysis of protein kinase data, however, is a challenge because of the disparate nature of protein kinase data sources and data formats. RESULTS: Here, we describe ProKinO, a protein kinase-specific ontology, which provides a controlled vocabulary of terms, their hierarchy, and relationships unifying sequence, structure, function, mutation and pathway information on protein kinases. The conceptual representation of such diverse forms of information in one place not only allows rapid discovery of significant information related to a specific protein kinase, but also enables large-scale integrative analysis of protein kinase data in ways not possible through other kinase-specific resources. We have performed several integrative analyses of ProKinO data and, as an example, found that a large number of somatic mutations (∼288 distinct mutations associated with the haematopoietic neoplasm cancer type map to only 8 kinases in the human kinome. This is in contrast to glioma, where the mutations are spread over 82 distinct kinases. We also provide examples of how ontology-based data analysis can be used to generate testable hypotheses regarding cancer mutations. CONCLUSION: We present an integrated framework for large-scale integrative analysis of protein kinase data. Navigation and analysis of ontology data can be performed using the ontology browser available at: http://vulcan.cs.uga.edu/prokino.

  10. Recurrent venous thromboembolism in anticoagulated patients with cancer : management and short-term prognosis

    NARCIS (Netherlands)

    Schulman, S.; Zondag, M.; Linkins, L.; Pasca, S.; Cheung, Y. W.; De Sancho, M.; Gallus, A.; Lecumberri, R.; Molnar, S.; Ageno, W.; Le Gal, G.; Falanga, A.; Hulegardh, E.; Ranta, S.; Kamphuisen, P.; Debourdeau, P.; Rigamonti, V.; Ortel, T. L.; Lee, A.

    2015-01-01

    BackgroundRecommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagul

  11. The short-term outcomes of conventional and single-port laparoscopic surgery for rectal cancer

    DEFF Research Database (Denmark)

    Levic, Katarina; Bulut, Orhan

    2014-01-01

    BACKGROUND: Single-port laparoscopic surgery (SPLS) has evolved as an alternative method to conventional laparoscopic surgery (CLS). The aim of this study is to evaluate the results of SPLS compared to CLS in the treatment of rectal cancer. MATERIAL AND METHODS: Prospectively collected data...

  12. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRi) plasmids | Office of Cancer Genomics

    Science.gov (United States)

    CTD2 researchers at the University of California in San Francisco developed a modified Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) CRISPR/dCas9 system. Catalytically inactive dCas9 enables modular and programmable RNA-guided genome regulation in eukaryotes.

  13. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRi) plasmids | Office of Cancer Genomics

    Science.gov (United States)

    CTD2 researchers at the University of California in San Francisco developed a modified Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) CRISPR/dCas9 system. Catalytically inactive dCas9 enables modular and programmable RNA-guided genome regulation in eukaryotes.

  14. Integrated proteomic and genomic analysis of colorectal cancer

    Science.gov (United States)

    Investigators who analyzed 95 human colorectal tumor samples have determined how gene alterations identified in previous analyses of the same samples are expressed at the protein level. The integration of proteomic and genomic data, or proteogenomics, pro

  15. An integrative review of South African cancer nursing research published from 2002–2012

    Directory of Open Access Journals (Sweden)

    Johanna Maree

    2014-02-01

    Full Text Available Background: This integrative review aimed to quantify the publication output of South African cancer nursing research conducted between 2002 and 2012 and to identify key trends relevant to cancer nurse researchers.Objectives: To describe the publication output of cancer nursing research in terms of the journals of publication, authors, focus, participants and methods used, to explore whether the published work was funded and to assess the quality of the studies published.Methods: An integrative review was conducted using the key words South Africa in combination with cancer nursing and oncology nursing to search the databases Pubmed, PsycINFO, CINAHL, Sabinet, Web of Science, Medline and OvidSP. A data extraction sheet was developed to document the required information from each paper and all publications were reviewed independently by the authors.Results: A total of 181 publications for potential inclusion were identified and 26 papers were included in this review. Cervical cancer, specifically the prevention of this disease, was the most popular diagnostic focus and theme of investigation. Most of the studies were descriptive and none of the studies met the criteria of the highest quality.Conclusion: Nursing added to the body of knowledge regarding the primary and secondary prevention of cancer. There is a need for work on both men and women diagnosed withthe most common cancers, as well as the family and care giver. There is also a need for multidisciplinary work using complex interventions focusing on symptom management to improve patient outcomes.

  16. Identifying master regulators of cancer and their downstream targets by integrating genomic and epigenomic features.

    Science.gov (United States)

    Gevaert, Olivier; Plevritis, Sylvia

    2013-01-01

    Vast amounts of molecular data characterizing the genome, epigenome and transcriptome are becoming available for a variety of cancers. The current challenge is to integrate these diverse layers of molecular biology information to create a more comprehensive view of key biological processes underlying cancer. We developed a biocomputational algorithm that integrates copy number, DNA methylation, and gene expression data to study master regulators of cancer and identify their targets. Our algorithm starts by generating a list of candidate driver genes based on the rationale that genes that are driven by multiple genomic events in a subset of samples are unlikely to be randomly deregulated. We then select the master regulators from the candidate driver and identify their targets by inferring the underlying regulatory network of gene expression. We applied our biocomputational algorithm to identify master regulators and their targets in glioblastoma multiforme (GBM) and serous ovarian cancer. Our results suggest that the expression of candidate drivers is more likely to be influenced by copy number variations than DNA methylation. Next, we selected the master regulators and identified their downstream targets using module networks analysis. As a proof-of-concept, we show that the GBM and ovarian cancer module networks recapitulate known processes in these cancers. In addition, we identify master regulators that have not been previously reported and suggest their likely role. In summary, focusing on genes whose expression can be explained by their genomic and epigenomic aberrations is a promising strategy to identify master regulators of cancer.

  17. A short-term sublethal toxicity assay with zebra fish based on preying rate and its integration with mortality.

    Science.gov (United States)

    Abdel-moneim, Ahmed; Moreira-Santos, Matilde; Ribeiro, Rui

    2015-02-01

    Contaminant-induced feeding inhibition has direct and immediate consequences at higher levels of biological organization, by depressing the population consumption and thus hampering ecosystem functioning (e.g. grazing, organic matter decomposition). Thus, similarly to lethality and avoidance, feeding is mechanistically linked to ecosystem processes and is therefore an unequivocal ecologically meaningful response. The objective of the present study was to develop a short-term assay with the small freshwater fish Danio rerio, based on feeding. For this, a methodology to easily and precisely quantify feeding was first optimized: each fish was allowed to prey on ten live Daphnia magna juveniles, for 1h, just before the end of a 48-h exposure test period. Secondly, copper sensitivity of feeding relatively to survival and growth was evaluated. At the growth EC20 (40 μg L(-1)), feeding was inhibited by 53%, and at the feeding EC50 (36 μg L(-1)), mortality was negligible (1.3%). Integrating feeding and survival revealed a 97% depression in the population consumption at the LC50 (61 μg L(-1)). Thirdly, the influence of pH, conductivity and hardness on the feeding background variability was assessed by assaying waters collected at eight reference sites and was found to be negligible, within tested ranges. Fourthly, feeding assays with natural waters contaminated with acid mine drainage confirmed the integration of lethality and feeding to be pertinent at estimating contaminant effects at higher levels of biological organization.

  18. An integral equation and simulation study of hydrogen inclusions in a molecular crystal of short-capped nanotubes

    Science.gov (United States)

    Lomba, Enrique; Bores, Cecilia; Notario, Rafael; Sánchez-Gil, V.

    2016-09-01

    In this work we have assessed the ability of a recently proposed three-dimensional integral equation approach to describe the explicit spatial distribution of molecular hydrogen confined in a crystal formed by short-capped nanotubes of C50 H10. To that aim we have resorted to extensive molecular simulation calculations whose results have been compared with our three-dimensional integral equation approximation. We have first tested the ability of a single C50 H10 nanocage for the encapsulation of H2 by means of molecular dynamics simulations, in particular using targeted molecular dynamics to estimate the binding Gibbs energy of a host hydrogen molecule inside the nanocage. Then, we have investigated the adsorption isotherm of the nanocage crystal using grand canonical Monte Carlo simulations in order to evaluate the maximum load of molecular hydrogen. For a packing close to the maximum load explicit hydrogen density maps and density profiles have been determined using molecular dynamics simulations and the three-dimensional Ornstein-Zernike equation with a hypernetted chain closure. In these conditions of extremely tight confinement the theoretical approach has shown to be able to reproduce the three-dimensional structure of the adsorbed fluid with accuracy down to the finest details.

  19. Demonstration of a time-integrated short line of sight neutron imaging system for inertial confinement fusion

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, R., E-mail: raspberry@lanl.gov; Danly, C.; Fatherley, V. E.; Merrill, F. E.; Volegov, P.; Wilde, C. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Christensen, K.; Fittinghoff, D.; Grim, G. P.; Izumi, N.; Jedlovec, D.; Skulina, K. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States)

    2015-12-15

    The Neutron Imaging System (NIS) is an important diagnostic for understanding implosions of deuterium-tritium capsules at the National Ignition Facility. While the detectors for the existing system must be positioned 28 m from the source to produce sufficient imaging magnification and resolution, recent testing of a new short line of sight neutron imaging system has shown sufficient resolution to allow reconstruction of the source image with quality similar to that of the existing NIS on a 11.6 m line of sight. The new system used the existing pinhole aperture array and a stack of detectors composed of 2 mm thick high-density polyethylene converter material followed by an image plate. In these detectors, neutrons enter the converter material and interact with protons, which recoil and deposit energy within the thin active layer of the image plate through ionization losses. The described system produces time-integrated images for all neutron energies passing through the pinhole. We present details of the measurement scheme for this novel technique to produce energy-integrated neutron images as well as source reconstruction results from recent experiments at NIF.

  20. Demonstration of a time-integrated short line of sight neutron imaging system for inertial confinement fusion

    Science.gov (United States)

    Simpson, R.; Christensen, K.; Danly, C.; Fatherley, V. E.; Fittinghoff, D.; Grim, G. P.; Izumi, N.; Jedlovec, D.; Merrill, F. E.; Skulina, K.; Volegov, P.; Wilde, C.

    2015-12-01

    The Neutron Imaging System (NIS) is an important diagnostic for understanding implosions of deuterium-tritium capsules at the National Ignition Facility. While the detectors for the existing system must be positioned 28 m from the source to produce sufficient imaging magnification and resolution, recent testing of a new short line of sight neutron imaging system has shown sufficient resolution to allow reconstruction of the source image with quality similar to that of the existing NIS on a 11.6 m line of sight. The new system used the existing pinhole aperture array and a stack of detectors composed of 2 mm thick high-density polyethylene converter material followed by an image plate. In these detectors, neutrons enter the converter material and interact with protons, which recoil and deposit energy within the thin active layer of the image plate through ionization losses. The described system produces time-integrated images for all neutron energies passing through the pinhole. We present details of the measurement scheme for this novel technique to produce energy-integrated neutron images as well as source reconstruction results from recent experiments at NIF.

  1. Integrating palliative care into the trajectory of cancer care.

    Science.gov (United States)

    Hui, David; Bruera, Eduardo

    2016-03-01

    Over the past five decades, palliative care has evolved from serving patients at the end of life into a highly specialized discipline focused on delivering supportive care to patients with life-limiting illnesses throughout the disease trajectory. A growing body of evidence is now available to inform the key domains in the practice of palliative care, including symptom management, psychosocial care, communication, decision-making, and end-of-life care. Findings from multiple studies indicate that integrating palliative care early in the disease trajectory can result in improvements in quality of life, symptom control, patient and caregiver satisfaction, illness understanding, quality of end-of-life care, survival, and costs of care. In this narrative Review, we discuss various strategies to integrate oncology and palliative care by optimizing clinical infrastructures, processes, education, and research. The goal of integration is to maximize patient access to palliative care and, ultimately, to improve patient outcomes. We provide a conceptual model for the integration of supportive and/or palliative care with primary and oncological care. We also discuss how health-care systems and institutions need to tailor integration based on their resources, size, and the level of primary palliative care available.

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

    Science.gov (United States)

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

    2015-01-01

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

  3. Development and preliminary validation of a short questionnaire based on the FDI 4-6 by Haeberlin, Moser, Bless, and Klaghofer measuring the educational integration of pupils

    Directory of Open Access Journals (Sweden)

    Martin Venetz

    2014-05-01

    Full Text Available The „Fragebogen zur Erfassung der Dimensionen der Integration von Schülern“ (FDI 4-6; Haeberlin, Moser, Bless & Klaghofer, 1989 is a self-report questionnaire measuring educational integration of pupils from an emotional, social, and motivational perspective. A short form comprising 12 items was developed on the basis of a sample of 744 pupils, and replicated using the sample of the original study (N = 1620. Confirmatory factor analyses support the postulated three-dimensional structure. Multiple group comparisons with respect to academic achievement, behavioural competencies, and linguistic background confirm the measurement equivalence of the short form. Internal consistencies of the three scales are satisfactory (. 80 ≤ a ≤ .91. As hypothesized, the scales are correlated with wellbeing in the classroom, behavioural competencies (teacher ratings, goal orientations, academic self-concept, and academic achievement. This short form KFDI 4-6 represents a reliable, valid, and highly economical instrument measuring the educational integration of pupils.

  4. Clinical Significance of the Prognostic Nutritional Index for Predicting Short- and Long-Term Surgical Outcomes After Gastrectomy: A Retrospective Analysis of 7781 Gastric Cancer Patients.

    Science.gov (United States)

    Lee, Jee Youn; Kim, Hyoung-Il; Kim, You-Na; Hong, Jung Hwa; Alshomimi, Saeed; An, Ji Yeong; Cheong, Jae-Ho; Hyung, Woo Jin; Noh, Sung Hoon; Kim, Choong-Bai

    2016-05-01

    To evaluate the predictive and prognostic significance of the prognostic nutritional index (PNI) in a large cohort of gastric cancer patients who underwent gastrectomy.Assessing a patient's immune and nutritional status, PNI has been reported as a predictive marker for surgical outcomes in various types of cancer.We retrospectively reviewed data from a prospectively maintained database of 7781 gastric cancer patients who underwent gastrectomy from January 2001 to December 2010 at a single center. From this data, we analyzed clinicopathologic characteristics, PNI, and short- and long-term surgical outcomes for each patient. We used the PNI value for the 10th percentile (46.70) of the study cohort as a cut-off for dividing patients into low and high PNI groups.Regarding short-term outcomes, multivariate analysis showed a low PNI (odds ratio [OR] = 1.505, 95% CI = 1.212-1.869, P cancer recurrence.

  5. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer

    NARCIS (Netherlands)

    Peifer, Martin; Fernandez-Cuesta, Lynnette; Sos, Martin L.; George, Julie; Seidel, Danila; Kasper, Lawryn H.; Plenker, Dennis; Leenders, Frauke; Sun, Ruping; Zander, Thomas; Menon, Roopika; Koker, Mirjam; Dahmen, Ilona; Mueller, Christian; Di Cerbo, Vincenzo; Schildhaus, Hans-Ulrich; Altmueller, Janine; Baessmann, Ingelore; Becker, Christian; de Wilde, Bram; Vandesompele, Jo; Boehm, Diana; Ansen, Sascha; Gabler, Franziska; Wilkening, Ines; Heynck, Stefanie; Heuckmann, Johannes M.; Lu, Xin; Carter, Scott L.; Cibulskis, Kristian; Banerji, Shantanu; Getz, Gad; Park, Kwon-Sik; Rauh, Daniel; Gruetter, Christian; Fischer, Matthias; Pasqualucci, Laura; Wright, Gavin; Wainer, Zoe; Russell, Prudence; Petersen, Iver; Chen, Yuan; Stoelben, Erich; Ludwig, Corinna; Schnabel, Philipp; Hoffmann, Hans; Muley, Thomas; Brockmann, Michael; Engel-Riedel, Walburga; Muscarella, Lucia A.; Fazio, Vito M.; Groen, Harry; Timens, Wim; Sietsma, Hannie; Thunnissen, Erik; Smit, Egbert; Heideman, Danielle A. M.; Snijders, Peter J. F.; Cappuzzo, Federico; Ligorio, Claudia; Damiani, Stefania; Field, John; Solberg, Steinar; Brustugun, Odd Terje; Lund-Iversen, Marius; Saenger, Joerg; Clement, Joachim H.; Soltermann, Alex; Moch, Holger; Weder, Walter; Solomon, Benjamin; Soria, Jean-Charles; Validire, Pierre; Besse, Benjamin; Brambilla, Elisabeth; Brambilla, Christian; Lantuejoul, Sylvie; Lorimier, Philippe; Schneider, Peter M.; Hallek, Michael; Pao, William; Meyerson, Matthew; Sage, Julien; Shendure, Jay; Schneider, Robert; Buettner, Reinhard; Wolf, Juergen; Nuernberg, Peter; Perner, Sven; Heukamp, Lukas C.; Brindle, Paul K.; Haas, Stefan; Thomas, Roman K.

    2012-01-01

    Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analys

  6. Strategies for Integrated Analysis of Genetic, Epigenetic, and Gene Expression Variation in Cancer

    DEFF Research Database (Denmark)

    Thingholm, Louise B; Andersen, Lars; Makalic, Enes

    2016-01-01

    The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis. H...

  7. Integration of early specialist palliative care in cancer care: Survey of oncologists, oncology nurses, and patients

    Directory of Open Access Journals (Sweden)

    Naveen Salins

    2016-01-01

    Conclusion: Oncologists, oncology nurses, and patients felt that integration of early specialist palliative care in cancer improves symptom control, end-of-life care, health-related communication, and continuity of care. The perceptions of benefit of the palliative care intervention in the components surveyed, differed among the three groups.

  8. Sperm integrity pre- and post-chemotherapy in men with testicular germ cell cancer.

    NARCIS (Netherlands)

    Spermon, J.R.; Ramos, L.; Wetzels, A.M.M.; Sweep, C.G.J.; Braat, D.D.M.; Kiemeney, L.A.L.M.; Witjes, J.A.

    2006-01-01

    BACKGROUND: While (partial) recovery of spermatogenesis, observed by means of standard semen analysis, has been seen in testicular cancer patients after chemotherapy with cisplatin, sperm genomic integrity and its implication for the patient's fertility are poorly understood. METHODS: Semen and seru

  9. No differences in short-term morbidity and mortality after robot-assisted laparoscopic versus laparoscopic resection for colonic cancer

    DEFF Research Database (Denmark)

    Helvind, Neel Maria; Eriksen, Jens Ravn; Mogensen, Anders Skibsted

    2013-01-01

    BACKGROUND: Robot-assisted laparoscopy has been reported to be a safe and feasible alternative to traditional laparoscopy. The aim of this study was to compare short-term results in patients with colonic cancer who underwent robot-assisted laparoscopic colonic resection (RC) or laparoscopic colonic...... journals. Biochemical markers [C-reactive protein (CRP), hemoglobin, white blood cell count, and thrombocyte count] were recorded before surgery and for the first 3 days after surgery. RESULTS: A total of 101 patients underwent RC and 162 patients underwent LC. There were no significant differences...... in the rate of conversion to open surgery, number of permanent enterostomies, number of intraoperative complications, level of postoperative cellular stress response, number of postoperative complications, length of postoperative hospital stay, or 30-day mortality between the two groups...

  10. Marginal pulmonary function is associated with poor short- and long-term outcomes in lung cancer surgery

    Science.gov (United States)

    Ozeki, Naoki; Kawaguchi, Koji; Okasaka, Toshiki; Fukui, Takayuki; Fukumoto, Koichi; Nakamura, Shota; Hakiri, Shuhei; Yokoi, Kohei

    2017-01-01

    ABSTRACT We sought to determine the short- and long-term prognoses among ‘marginal-risk’ non-small cell lung cancer patients who have a predicted postoperative- (ppo) forced expiratory volume in the first second (FEV1) of 30–60% and/or a ppo-diffusing capacity of the lung for carbon monoxide (DLCO) of 30–60%. The present study included 73 ‘marginal-risk’ and 318 ‘normal-risk’ patients who underwent anatomical resection for clinical stage I lung cancer between 2008 and 2012. The rates of postoperative morbidity, prolonged hospital stay, and overall survival were assessed. Postoperative morbidity occurred in 35 (48%) ‘marginal-risk’ patients and 66 (21%) ‘normal-risk’ patients, and 17 (23%) ‘marginal-risk’ patients and 20 (6%) ‘normal-risk’ patients required a prolonged hospital stay. The three- and five-year survival rates were 79% and 64% in the ‘marginal-risk’ patients and 93% and 87% in the ‘normal-risk’ patients, respectively. A ‘marginal-risk’ status was a significant factor in the prediction of postoperative morbidity (odds ratio [OR] 2.97, p < 0.001), the rate of prolonged hospital stay (OR 3.83, p < 0.001), and overall survival (hazard ratio 2.07, p = 0.028). In conclusion, ‘Marginal-risk’ patients, who are assessed based on ppo-values, comprise a subgroup of patients with poorer short- and long-term postoperative outcomes.

  11. Metformin for cancer and aging prevention: is it a time to make the long story short?

    Science.gov (United States)

    Anisimov, Vladimir N

    2015-11-24

    During the last decade, the burst of interest is observed to antidiabetic biguanide metformin as candidate drug for cancer chemoprevention. The analysis of the available data have shown that the efficacy of cancer preventive effect of metformin (MF) and another biguanides, buformin (BF) and phenformin (PF), has been studied in relation to total tumor incidence and to 17 target organs, in 21 various strains of mice, 4 strains of rats and 1 strain of hamsters (inbred, outbred, transgenic, mutant), spontaneous (non- exposed to any carcinogenic agent) or induced by 16 chemical carcinogens of different classes (polycycIic aromatic hydrocarbons, nitroso compounds, estrogen, etc.), direct or indirect (need metabolic transformation into proximal carcinogen), by total body X-rays and γ- irradiation, viruses, genetic modifications or special high fat diet, using one stage and two-stage protocols of carcinogenesis, 5 routes of the administration of antidiabetic biguanides (oral gavage, intraperitoneal or subcutaneous injections, with drinking water or with diet) in a wide ranks of doses and treatment regimens. In the majority of cases (86%) the treatment with biguanides leads to inhibition of carcinogenesis. In 14% of the cases inhibitory effect of the drugs was not observed. Very important that there was no any case of stimulation of carcinogenesis by antidiabetic biguanides. It was conclude that there is sufficient experimental evidence of anti-carcinogenic effect of antidiabetic biguanides.

  12. Metformin for cancer and aging prevention: is it a time to make the long story short?

    Science.gov (United States)

    Anisimov, Vladimir N.

    2015-01-01

    During the last decade, the burst of interest is observed to antidiabetic biguanide metformin as candidate drug for cancer chemoprevention. The analysis of the available data have shown that the efficacy of cancer preventive effect of metformin (MF) and another biguanides, buformin (BF) and phenformin (PF), has been studied in relation to total tumor incidence and to 17 target organs, in 21 various strains of mice, 4 strains of rats and 1 strain of hamsters (inbred, outbred, transgenic, mutant), spontaneous (non- exposed to any carcinogenic agent) or induced by 16 chemical carcinogens of different classes (polycycIic aromatic hydrocarbons, nitroso compounds, estrogen, etc.), direct or indirect (need metabolic transformation into proximal carcinogen), by total body X-rays and γ- irradiation, viruses, genetic modifications or special high fat diet, using one stage and two-stage protocols of carcinogenesis, 5 routes of the administration of antidiabetic biguanides (oral gavage, intraperitoneal or subcutaneous injections, with drinking water or with diet) in a wide ranks of doses and treatment regimens. In the majority of cases (86%) the treatment with biguanides leads to inhibition of carcinogenesis. In 14% of the cases inhibitory effect of the drugs was not observed. Very important that there was no any case of stimulation of carcinogenesis by antidiabetic biguanides. It was conclude that there is sufficient experimental evidence of anti-carcinogenic effect of antidiabetic biguanides. PMID:26583576

  13. Single-Chip Fully Integrated Direct-Modulation CMOS RF Transmitters for Short-Range Wireless Applications

    Directory of Open Access Journals (Sweden)

    M. Jamal Deen

    2013-08-01

    Full Text Available Ultra-low power radio frequency (RF transceivers used in short-range application such as wireless sensor networks (WSNs require efficient, reliable and fully integrated transmitter architectures with minimal building blocks. This paper presents the design, implementation and performance evaluation of single-chip, fully integrated 2.4 GHz and 433 MHz RF transmitters using direct-modulation power voltage-controlled oscillators (PVCOs in addition to a 2.0 GHz phase-locked loop (PLL based transmitter. All three RF transmitters have been fabricated in a standard mixed-signal CMOS 0.18 µm technology. Measurement results of the 2.4 GHz transmitter show an improvement in drain efficiency from 27% to 36%. The 2.4 GHz and 433 MHz transmitters deliver an output power of 8 dBm with a phase noise of −122 dBc/Hz at 1 MHz offset, while drawing 15.4 mA of current and an output power of 6.5 dBm with a phase noise of −120 dBc/Hz at 1 MHz offset, while drawing 20.8 mA of current from 1.5 V power supplies, respectively. The PLL transmitter delivers an output power of 9 mW with a locking range of 128 MHz and consumes 26 mA from 1.8 V power supply. The experimental results demonstrate that the RF transmitters can be efficiently used in low power WSN applications.

  14. Integrative exercise and lifestyle intervention increases leisure-time activity in breast cancer patients

    DEFF Research Database (Denmark)

    Casla, Soraya; Hojman, Pernille; Cubedo, Ricardo

    2014-01-01

    BACKGROUND: Physical activity has been demonstrated to increase survival in breast cancer patients, but few breast cancer patients meet the general recommendations for physical activity. The aim of this pilot study was to investigate if a supervised integrated counseling and group-based exercise...... program could increase leisure-time activity in women with breast cancer. METHODS: This pilot project, designed as a single-arm study with pre-post testing, consisted of 24 classes of combined aerobic and strength exercise training as well as classes on dietary and health behavior. A total of 48 women...... with breast cancer who were undergoing or had recently completed anticancer treatment completed the study. Leisure-time physical activity, grip strength, functional capacity, quality of life (QoL), and depression were assessed at baseline, after intervention, and at the 12-week follow-up after intervention...

  15. HPV genotyping and site of viral integration in cervical cancers in Indian women.

    Directory of Open Access Journals (Sweden)

    Poulami Das

    Full Text Available Persistent HPV infection plays a major role in cervical cancer. This study was undertaken to identify HPV types in a cohort of Indian women with locally advanced cervical cancer as well as to determine the physical state and/or site of viral integration in the host genome. Pretreatment biopsies (n = 270 from patients were screened for HPV infection by a high throughput HPV genotyping assay based on luminex xMAP technology as well as MY09/11 PCR and SPF1/2 PCR. Overall HPV positivity was observed to be 95%, with HPV16 being most common (63% followed by infection with HPV18. Integration status of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT assay in a subset of samples positive for HPV16 and/or HPV18 (n = 86 and with an adequate follow-up. The data was correlated with clinical outcome of the patients. Integration of the viral genome was observed in 79% of the cases and a preference for integration into the chromosomal loci 1p, 3q, 6q, 11q, 13q and 20q was seen. Clinical data revealed that the physical state of the virus (integrated or episomal could be an important prognostic marker for cervical cancer.

  16. Parity and Short-Term Estradiol Treatment Utilizes Similar Cellular Mechanisms to Confer Protection Against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Arunkumar Arumugam

    2014-08-01

    Full Text Available Background: Protective effect of early pregnancy and short-term estrogen treatment (STET, against breast cancer is well established. The underlying mechanisms are not well understood. In this study, we compared the mammary gland cellular microenvironment influenced/induced by parity and STET alongside age-matched controls. Methods: Parous, STET, and control rats were injected with N-methyl-N-nitrosourea at 15 weeks and monitored for the development of mammary cancer. A subset of 4 rats were killed five weeks post carcinogen treatment and mammary gland samples were isolated and subjected to molecular analysis. Results: Our results demonstrated a reduction in cell survival, extracellular matrix associated proliferation, hormonal and growth factor receptor pathways in the experimental groups compared to control rats. Moreover, concomitant reductions in the EMT markers along with cell migration regulators were also observed in parous and STET groups. Hormonal receptor such as GHR, PR, ERα and growth factor receptors IGFR, EGFR and erbB2 were down regulated in the treatment groups. Further analysis revealed that parity and STET drastically reduced the expression, activation of JAK2 and nuclear localization of STATs. Conclusion: Parity and STET by targeting major cell signaling pathways involved in cell survival, cell migration and cell death reduces the mammary tumor promoting environment.

  17. Strategies for Integrated Analysis of Genetic, Epigenetic, and Gene Expression Variation in Cancer: Addressing the Challenges

    DEFF Research Database (Denmark)

    Thingholm, Louise Bruun; Andersen, Lars; Makalic, Enes

    2016-01-01

    The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis....... However, integration of heterogeneous measurements of biological variation is a non-trivial exercise due to the diversity of the human genome and the variety of output data formats and genome coverage obtained from the commonly used molecular platforms. This review article will provide an introduction...... to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured...

  18. An integrative review of guidelines for anal cancer screening in HIV-infected persons.

    Science.gov (United States)

    Wells, Jessica S; Holstad, Marcia M; Thomas, Tami; Bruner, Deborah Watkins

    2014-07-01

    HIV-infected individuals are 28 times more likely than the general population to be diagnosed with anal cancer. An integrative review of recommendations and guidelines for anal cancer screening was performed to provide a succinct guide to inform healthcare clinicians. The review excluded studies that were of non-HIV populations, redundant articles or publications, non-English manuscripts, or nonclinical trials. The review found no formal national or international guidelines exist for routine screening of anal cancer for HIV-infected individuals. To date, no randomized control trial provides strong evidence supporting efficaciousness and effectiveness of an anal cancer screening program. The screening recommendations from seven international-, national-, and state-based reports were reviewed and synthesized in this review. These guidelines suggest anal cancer screening, albeit unproven, may be beneficial at decreasing the incidence of anal cancer. This review highlights the paucity of screening-related research and is an area of need to provide clear direction and to define standard of care for anal cancer screening in HIV-infected persons.

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

    Directory of Open Access Journals (Sweden)

    Chihyun Park

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

  20. Quality of Life among Female Cancer Survivors in Africa: An Integrative Literature Review

    Science.gov (United States)

    Muliira, Rhoda Suubi; Salas, Anna Santos; O’Brien, Beverley

    2017-01-01

    Quality of life (QOL) has been studied extensively among cancer populations in high income countries where cancer care resources are available to many. Little is known concerning the QOL of cancer groups residing in Africa where resources can be scarce. The integrative review of the literature explored and critically examined studies that had addressed QOL in female cancer survivors in Africa. The extent to which QOL studies incorporated a cultural perspective was also examined. Research studies published between 2005 and 2015 were retrieved from five databases: CINAHL, MEDLINE, SCOPUS, ProQuest dissertations and Theses full text, and GlobalHealth. Primary qualitative or quantitative studies regardless of sample size or setting were included. A total of 300 studies were identified and 28 full text studies were retrieved and assessed for eligibility. Eight studies met inclusion criteria. Factors that affected the QOL were socio-demographic especially age, education, employment, income and residence; illness-related factors such as having advanced cancer and multiple symptoms; treatment-related factors associated with surgery and radiotherapy; psychosocial factors such as support and anxiety; and cultural factors including fatalism and bewitching. Practice implications entail increasing awareness among nurses and allied healthcare providers of the potential effects on QOL of a cancer diagnosis and treatment of female cancers such as pain, fatigue, sexual dysfunction, hormonal and body image changes, anxiety, depression and cultural practices. Failure to identify and deal with these may result in poor treatment adherence, low self-esteem, and ultimately poor QOL. PMID:28217724

  1. Quality of life among female cancer survivors in Africa: An integrative literature review

    Directory of Open Access Journals (Sweden)

    Rhoda Suubi Muliira

    2017-01-01

    Full Text Available Quality of life (QOL has been studied extensively among cancer populations in high income countries where cancer care resources are available to many. Little is known concerning the QOL of cancer groups residing in Africa where resources can be scarce. The integrative review of the literature explored and critically examined studies that had addressed QOL in female cancer survivors in Africa. The extent to which QOL studies incorporated a cultural perspective was also examined. Research studies published between 2005 and 2015 were retrieved from five databases: CINAHL, MEDLINE, SCOPUS, ProQuest dissertations and Theses full text, and GlobalHealth. Primary qualitative or quantitative studies regardless of sample size or setting were included. A total of 300 studies were identified and 28 full text studies were retrieved and assessed for eligibility. Eight studies met inclusion criteria. Factors that affected the QOL were socio-demographic especially age, education, employment, income and residence; illness-related factors such as having advanced cancer and multiple symptoms; treatment-related factors associated with surgery and radiotherapy; psychosocial factors such as support and anxiety; and cultural factors including fatalism and bewitching. Practice implications entail increasing awareness among nurses and allied healthcare providers of the potential effects on QOL of a cancer diagnosis and treatment of female cancers such as pain, fatigue, sexual dysfunction, hormonal and body image changes, anxiety, depression and cultural practices. Failure to identify and deal with these may result in poor treatment adherence, low self-esteem, and ultimately poor QOL.

  2. Electromagnetic-Thermal Integrated Design Optimization for Hypersonic Vehicle Short-Time Duty PM Brushless DC Motor

    Directory of Open Access Journals (Sweden)

    Quanwu Li

    2016-01-01

    Full Text Available High reliability is required for the permanent magnet brushless DC motor (PM-BLDCM in an electrical pump of hypersonic vehicle. The PM-BLDCM is a short-time duty motor with high-power-density. Since thermal equilibrium is not reached for the PM-BLDCM, the temperature distribution is not uniform and there is a risk of local overheating. The winding is a main heat source and its insulation is thermally sensitive, so reducing the winding temperature rise is the key to the improvement of the reliability. In order to reduce the winding temperature rise, an electromagnetic-thermal integrated design optimization method is proposed. The method is based on electromagnetic analysis and thermal transient analysis. The requirements and constraints of electromagnetic and thermal design are considered in this method. The split ratio and the maximum flux density in stator lamination, which are highly relevant to the windings temperature rise, are optimized analytically. The analytical results are verified by finite element analysis (FEA and experiments. The maximum error between the analytical and the FEA results is 4%. The errors between the analytical and measured windings temperature rise are less than 8%. It can be proved that the method can obtain the optimal design accurately to reduce the winding temperature rise.

  3. A Service Oriented Architecture to Integrate Short Message Service (SMS Notification in Road Traffic Volume Control System

    Directory of Open Access Journals (Sweden)

    Zahi Abu Sarhan

    2013-02-01

    Full Text Available The traffic volume becomes one of the top problems in the world, the volume of traffic spends many time and much money, the traffic volume grows daily, and there is not effective and suitable solutions for grows problem. This paper will present and describe an effective approach to integrate the Service Oriented Architecture with mobile devices and services agents in Traffic Management Systems (TMS. The Traffic Volume Control System (TVCS should enable mobile short message service (SMS notifications. Unfortunately, cellular SMS notification based on services that are not aspect of the TVCS.Developing altered exterior systems and services, to be virtually aspect of TVCS, are one of the most incorporation difficulties. In this paper, a Service Oriented Architecture (SOA approach to includecellular SMS alerts in TVCS is presented. Suggested Structure includes two layers: Service layer and Interface layer. The Service layer includes all the system software. The service layer consists of three sub layers: Orchestration, Application Services, and Agents sub-layers. While the Interface layer interrelates with speed detectors and users via sites, and with exterior organization services via Web services.

  4. Keplerian integrals, elimination theory and identification of very short arcs in a large database of optical observations

    CERN Document Server

    Gronchi, Giovanni Federico; Milani, Andrea

    2016-01-01

    The modern optical telescopes produce a huge number of asteroid observations, that are grouped into very short arcs (VSAs), each containing a few observations of the same object in one single night. To decide whether two VSAs, collected in different nights, refer to the same observed object we can attempt to compute an orbit with the observations of both arcs: this is called the linkage problem. Since the number of orbit computations to be performed is very large, we need efficient methods of orbit determination. Using the first integrals of Kepler's motion we can write algebraic equations for the linkage problem, which can be put in polynomial form. The equations introduced in (Gronchi et al. 2015) can be reduced to a univariate polynomial of degree 9: the unknown is the topocentric distance $\\rho$ of the observed body at the mean epoch of one of the VSAs. Using elimination theory we show an optimal property of this polynomial: it has the least degree among the univariate polynomials in the same variable tha...

  5. Short-term outcomes after complete mesocolic excision compared with 'conventional' colonic cancer surgery

    DEFF Research Database (Denmark)

    Bertelsen, C A; Neuenschwander, A U; Jansen, J E

    2016-01-01

    2008 to December 2013) were retrieved from the Danish Colorectal Cancer Group database and medical charts. Approval from a Danish ethics committee was not required (retrospective study). RESULTS: Some 529 patients who underwent CME surgery at one centre were compared with 1701 patients undergoing......BACKGROUND: Complete mesocolic excision (CME) seems to be associated with improved oncological outcomes compared with 'conventional' surgery, but there is a potential for higher morbidity. METHODS: Data for patients after elective resection at the four centres in the Capital Region of Denmark (June...... group was 6·2 per cent versus 4·9 per cent in the 'conventional' group (P = 0·219), with a propensity score-adjusted logistic regression odds ratio (OR) of 1·22 (95 per cent c.i. 0·79 to 1·87). Laparoscopic surgery was associated with a lower risk of mortality at 90 days (OR 0·63, 0·42 to 0...

  6. Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin; Yamada, Yoshiya; Kalikstein, Abraham [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kuk, Deborah; Zhang, Zhigang [Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Zelefsky, Michael J., E-mail: zelefskm@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)

    2013-03-15

    Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.

  7. Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers.

    Science.gov (United States)

    Power, D G; Ilson, D H

    2009-11-01

    Pre- and peri-operative strategies are becoming standard for the management of localized gastro-esophageal cancer. For localized gastric/gastro-esophageal junction (GEJ) cancer there are conflicting data that a peri-operative approach with cisplatin-based chemotherapy improves survival, with the benefits seen in esophageal cancer likely less than a 5-10% incremental improvement. Further trends toward improvement in local control and survival, when combined chemotherapy and radiation therapy are given pre-operatively, are suggested by recent phase III trials. In fit patients, a significant survival benefit with pre-operative chemoradiation is seen in those patients who achieve a pathologic complete response. In esophageal/GEJ cancer, definitive chemoradiation is now considered in medically inoperable patients. In squamous cell carcinoma of the esophagus, surgery after primary chemoradiation is not clearly associated with an improved overall survival, however, local control may be better. In localized gastric/GEJ cancer, the integration of bevacizumab with pre-operative chemotherapy is being explored in large randomized studies, and with chemoradiotherapy in pilot trials. The addition of anti-epidermal growth factor receptor and anti-human epidermal growth factor receptor-2 antibody treatment to pre-operative chemoradiation continues to be explored. Early results show the integration of targeted therapy is feasible. Metabolic imaging can predict early response to pre-operative chemotherapy and biomarkers may further predict response to pre-operative chemo-targeted therapy. A multimodality approach to localized gastro-esophageal cancer has resulted in better outcomes. For T3 or node-positive disease, surgery alone is no longer considered appropriate and neo-adjuvant therapy is recommended. The future of neo-adjuvant strategies in this disease will involve the individualization of therapy with the integration of molecular signatures, targeted therapy, metabolic imaging

  8. Relationship of short-course preoperative radiotherapy and serum albumin level with postoperative complications in rectal cancer surgery

    Directory of Open Access Journals (Sweden)

    Trifunović Bratislav

    2015-01-01

    Full Text Available Background/Aim. The identification of risk factors could play a role in improving early postoperative outcome for rectal cancer surgery patients. The aim of this study was to determine the relationship between short-course preoperative radiotherapy (RT, serum albumin level and the development of postoperative complications in patients after anterior rectal resection due to rectal cancer without creation of diverting stoma. Methods. This retrospective study included patients with histopathologically confirmed adenocarcinoma of the rectum by and the clinical stage of T2-T4 operated on between 2007 and 2012. All the patients underwent open anterior rectal resection with no diverting stoma creation. Preoperative serum albumin was measured in each patient. Tumor location was noted intraoperatively as the distance from the inferior tumor margin to the anal verge. Tumor size was measured and noted by the pathologist who assessed specimens. Some of the patients received short-course preoperative RT, and some did not. The patients were divided into two groups (group 1 with short-course preoperative RT, group 2 with no short-course preoperative RT. Postoperative complications included clinically apparent anastomotic leakage, wound infection, diffuse peritonitis and pneumonia. They were compared between the groups, in relation to preoperative serum albumin level, patients age, tumor size and location. Results. The study included 107 patients (51 in the group 1 and 56 in the group 2. There were no significant difference in age (p = 0.95, and gender (p = 0.12 and tumor distance from anal verge (p = 0.53. The size of rectal carcinoma was significantly higher in the group 1 than in the group 2 (51.37 ± 12.04 mm vs 45.57 ± 9.81 mm, respectively; p = 0.007. The preoperative serum albumin level was significantly lower in the group 1 than in the group 2 (34.80 ± 2.85 g/L vs 37.55 ± 2.74 g/L, respectively; p < 0.001. A significant correlation between the tumor

  9. SIGMA: A System for Integrative Genomic Microarray Analysis of Cancer Genomes

    Directory of Open Access Journals (Sweden)

    Davies Jonathan J

    2006-12-01

    Full Text Available Abstract Background The prevalence of high resolution profiling of genomes has created a need for the integrative analysis of information generated from multiple methodologies and platforms. Although the majority of data in the public domain are gene expression profiles, and expression analysis software are available, the increase of array CGH studies has enabled integration of high throughput genomic and gene expression datasets. However, tools for direct mining and analysis of array CGH data are limited. Hence, there is a great need for analytical and display software tailored to cross platform integrative analysis of cancer genomes. Results We have created a user-friendly java application to facilitate sophisticated visualization and analysis such as cross-tumor and cross-platform comparisons. To demonstrate the utility of this software, we assembled array CGH data representing Affymetrix SNP chip, Stanford cDNA arrays and whole genome tiling path array platforms for cross comparison. This cancer genome database contains 267 profiles from commonly used cancer cell lines representing 14 different tissue types. Conclusion In this study we have developed an application for the visualization and analysis of data from high resolution array CGH platforms that can be adapted for analysis of multiple types of high throughput genomic datasets. Furthermore, we invite researchers using array CGH technology to deposit both their raw and processed data, as this will be a continually expanding database of cancer genomes. This publicly available resource, the System for Integrative Genomic Microarray Analysis (SIGMA of cancer genomes, can be accessed at http://sigma.bccrc.ca.

  10. Salinomycin inhibits growth of pancreatic cancer and cancer cell migration by disruption of actin stress fiber integrity.

    Science.gov (United States)

    Schenk, Miriam; Aykut, Berk; Teske, Christian; Giese, Nathalia A; Weitz, Juergen; Welsch, Thilo

    2015-03-28

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by aggressive growth, early metastasis and high resistance to chemotherapy. Salinomycin is a promising compound eliminating cancer stem cells and retarding cancer cell migration. The present study investigated the effectiveness of salinomycin against PDAC in vivo and elucidated the mechanism of PDAC growth inhibition. Salinomycin treatment was well tolerated by the mice and significantly reduced tumor growth after 19 days compared to the control group (each n = 16). There was a trend that salinomycin also impeded metastatic spread to the liver and peritoneum. Whereas salinomycin moderately induced apoptosis and retarded proliferation at 5-10 µM, it strongly inhibited cancer cell migration that was accompanied by a marked loss of actin stress fibers after 6-9 h. Salinomycin silenced RhoA activity, and loss of stress fibers could be reversed by Rho activation. Moreover, salinomycin dislocated fascin from filopodia and stimulated Rac-associated circular dorsal ruffle formation. In conclusion, salinomycin is an effective and promising compound against PDAC. Besides its known stem cell-specific cytotoxic effects, salinomycin blocks cancer cell migration by disrupting stress fiber integrity and affecting the mutual Rho-GTPase balance.

  11. Combining process indicators to evaluate quality of care for surgical patients with colorectal cancer: are scores consistent with short-term outcome?

    NARCIS (Netherlands)

    Kolfschoten, N.E.; Gooiker, G.A.; Bastiaannet, E.; Leersum, N.J. van; Velde, C.J. van de; Eddes, E.H.; Marang-van de Mheen, P.J.; Kievit, J.; Harst, E. van der; Wiggers, T.; Wouters, M.W.; Tollenaar, R.A.E.M.; Krieken, J.H. van

    2012-01-01

    OBJECTIVE: To determine if composite measures based on process indicators are consistent with short-term outcome indicators in surgical colorectal cancer care. DESIGN: Longitudinal analysis of consistency between composite measures based on process indicators and outcome indicators for 85 Dutch hosp

  12. Combining process indicators to evaluate quality of care for surgical patients with colorectal cancer : are scores consistent with short-term outcome?

    NARCIS (Netherlands)

    Kolfschoten, N. E.; Gooiker, G. A.; Bastiaannet, E.; van Leersum, N. J.; van de Velde, C. J. H.; Eddes, E. H.; Marang-van de Mheen, P. J.; Kievit, J.; van der Harst, E.; Wiggers, T.; Wouters, M. W. J. M.; Tollenaar, R. A. E. M.

    2012-01-01

    Objective: To determine if composite measures based on process indicators are consistent with short-term outcome indicators in surgical colorectal cancer care. Design: Longitudinal analysis of consistency between composite measures based on process indicators and outcome indicators for 85 Dutch hosp

  13. The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study

    NARCIS (Netherlands)

    Groot, S. de; Vreeswijk, M.P.; Welters, M.J.; Gravesteijn, G.; Boei, J.J.; Jochems, A.; Houtsma, D.; Putter, H.; Hoeven, J.J.M. van der; Nortier, J.W.; Pijl, H.; Kroep, J.R.

    2015-01-01

    BACKGROUND: Preclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer cells more vulnerable to it. This pilot study examines the feasibility of STF and its effects on tolerance of chemotherapy in a homogeneous patient group

  14. Short treatment time and excellent treatment outcome in accelerated hyperfractionated radiotherapy for T1 glottic cancer.

    Science.gov (United States)

    Tamaki, Yukihisa; Hieda, Yoko; Yoshida, Rika; Yoshizako, Takeshi; Fuchiwaki, Takafumi; Aoi, Noriaki; Sekihara, Kazumasa; Kitajima, Kazuhiro; Kawauchi, Hideyuki; Kitagaki, Hajime; Sasaki, Ryohei; Inomata, Taisuke

    2015-11-01

    Accelerated hyperfractionated radiotherapy was performed as treatment for patients with T1 glottic cancer, and its utility was evaluated based on treatment outcomes and adverse effects. Fifty-eight men who had undergone radiotherapy were retrospectively reviewed. Tumor classification was Tis in 4 patients, T1a in 38, and T1b in 16. Histological examination revealed squamous cell carcinoma in 55 patients. Travel time from home to hospital was 0-1 hour for 24 patients, 1-2 hours for 9, and >2 hours for 25. Laser vaporization was performed prior to radiotherapy in 38 patients, and 19 patients received concurrent chemotherapy with an agent such as S-1. Patients were irradiated twice daily using an irradiation container. Most patients received a dose of 1.5 Gy/fraction up to a total of 60 Gy. The median overall treatment time was 30 days, with a median observation period of 59.6 months. A complete response was observed in all patients. The 5-year overall survival, disease-free survival, and local control rates were 97.2%, 93.2%, and 97.8%, respectively. Although grade 3 pharyngeal mucositis was observed in 2 patients, there were no other grade 3 or higher acute adverse events. As late toxicity, grade 2 laryngeal edema and grade 1 laryngeal hemorrhage were observed in 1 patient each, but no serious events such as laryngeal necrosis or laryngeal stenosis were observed. In conclusion, this treatment method brings excellent outcome and will substantially reduce the treatment duration among patients who need to stay at nearby hotels while undergoing treatment at hospitals in rural areas.

  15. Keplerian integrals, elimination theory and identification of very short arcs in a large database of optical observations

    Science.gov (United States)

    Gronchi, G. F.; Baù, G.; Milani, A.

    2016-09-01

    Modern asteroid surveys produce an increasingly large number of observations, which are grouped into very short arcs (VSAs) each containing a few observations of the same object in one single night. To decide whether two VSAs collected in different nights correspond to the same observed object we can attempt to compute an orbit with the observations of both arcs: this is called the linkage problem. Since the number of linkages to be attempted is very large, we need efficient methods of orbit determination. Using the first integrals of Kepler's motion we can write algebraic equations for the linkage problem, which can be put in polynomial form. In Gronchi et al. (Celest Mech Dyn Astron 123(2):105-122, 2015) these equations are reduced to a polynomial equation of degree 9: the unknown is the topocentric distance of the observed body at the mean epoch of one VSA. Here we derive the same equations in a more concise way, and show that the degree 9 is optimal in a sense that will be specified in Sect. 3.3. We also introduce a procedure to join three VSAs: from the conservation of angular momentum we obtain a polynomial equation of degree 8 in the topocentric distance at the mean epoch of the second VSA. For both identification methods, with two and three VSAs, we discuss how to discard solutions. Finally, we present some numerical tests showing that the new methods give satisfactory results and can be used also when the time separation between the VSAs is large. The low polynomial degree of the new methods makes them well suited to deal with the very large number of asteroid observations collected by the modern surveys.

  16. Keplerian integrals, elimination theory and identification of very short arcs in a large database of optical observations

    Science.gov (United States)

    Gronchi, G. F.; Baù, G.; Milani, A.

    2017-02-01

    Modern asteroid surveys produce an increasingly large number of observations, which are grouped into very short arcs (VSAs) each containing a few observations of the same object in one single night. To decide whether two VSAs collected in different nights correspond to the same observed object we can attempt to compute an orbit with the observations of both arcs: this is called the linkage problem. Since the number of linkages to be attempted is very large, we need efficient methods of orbit determination. Using the first integrals of Kepler's motion we can write algebraic equations for the linkage problem, which can be put in polynomial form. In Gronchi et al. (Celest Mech Dyn Astron 123(2):105-122, 2015) these equations are reduced to a polynomial equation of degree 9: the unknown is the topocentric distance of the observed body at the mean epoch of one VSA. Here we derive the same equations in a more concise way, and show that the degree 9 is optimal in a sense that will be specified in Sect. 3.3. We also introduce a procedure to join three VSAs: from the conservation of angular momentum we obtain a polynomial equation of degree 8 in the topocentric distance at the mean epoch of the second VSA. For both identification methods, with two and three VSAs, we discuss how to discard solutions. Finally, we present some numerical tests showing that the new methods give satisfactory results and can be used also when the time separation between the VSAs is large. The low polynomial degree of the new methods makes them well suited to deal with the very large number of asteroid observations collected by the modern surveys.

  17. Cancer panomics: computational methods and infrastructure for integrative analysis of cancer high-throughput "omics" data

    DEFF Research Database (Denmark)

    Brunak, Søren; De La Vega, Francisco M.; Rätsch, Gunnar

    2014-01-01

    Targeted cancer treatment is becoming the goal of newly developed oncology medicines and has already shown promise in some spectacular cases such as the case of BRAF kinase inhibitors in BRAF-mutant (e.g. V600E) melanoma. These developments are driven by the advent of high-throughput sequencing...

  18. IBPRO - A Novel Short-Duration Teaching Course in Advanced Physics and Biology Underlying Cancer Radiotherapy.

    Science.gov (United States)

    Joiner, Michael C; Tracey, Monica W; Kacin, Sara E; Burmeister, Jay W

    2017-03-22

    This article provides a summary and status report of the ongoing advanced education program IBPRO - Integrated course in Biology and Physics of Radiation Oncology. IBPRO is a five-year program funded by NCI. It addresses the recognized deficiency in the number of mentors available who have the required knowledge and skill to provide the teaching and training that is required for future radiation oncologists and researchers in radiation sciences. Each year, IBPRO brings together 50 attendees typically at assistant professor level and upwards, who are already qualified/certified radiation oncologists, medical physicists or biologists. These attendees receive keynote lectures and activities based on active learning strategies, merging together the clinical, biological and physics underpinnings of radiation oncology, at the forefront of the field. This experience is aimed at increasing collaborations, raising the level and amount of basic and applied research undertaken in radiation oncology, and enabling attendees to confidently become involved in the future teaching and training of researchers and radiation oncologists.

  19. An integrated approach to blood-based cancer diagnosis and biomarker discovery.

    Science.gov (United States)

    Min, Martin Renqiang; Chowdhury, Salim; Qi, Yanjun; Stewart, Alex; Ostroff, Rachel

    2014-01-01

    Disrupted or abnormal biological processes responsible for cancers often quantitatively manifest as disrupted additive and multiplicative interactions of gene/protein expressions correlating with cancer progression. However, the examination of all possible combinatorial interactions between gene features in most case-control studies with limited training data is computationally infeasible. In this paper, we propose a practically feasible data integration approach, QUIRE (QUadratic Interactions among infoRmative fEatures), to identify discriminative complex interactions among informative gene features for cancer diagnosis and biomarker discovery directly based on patient blood samples. QUIRE works in two stages, where it first identifies functionally relevant gene groups for the disease with the help of gene functional annotations and available physical protein interactions, then it explores the combinatorial relationships among the genes from the selected informative groups. Based on our private experimentally generated data from patient blood samples using a novel SOMAmer (Slow Off-rate Modified Aptamer) technology, we apply QUIRE to cancer diagnosis and biomarker discovery for Renal Cell Carcinoma (RCC) and Ovarian Cancer (OVC). To further demonstrate the general applicability of our approach, we also apply QUIRE to a publicly available Colorectal Cancer (CRC) dataset that can be used to prioritize our SOMAmer design. Our experimental results show that QUIRE identifies gene-gene interactions that can better identify the different cancer stages of samples, as compared to other state-of-the-art feature selection methods. A literature survey shows that many of the interactions identified by QUIRE play important roles in the development of cancer.

  20. Comparison of preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Guckenberger, M.; Saur, G.; Wehner, D.; Sweeney, R.A.; Flentje, M. [Universitaetsklinikum Wuerzburg (Germany). Klinik und Poliklinik fuer Strahlentherapie; Thalheimer, A.; Germer, C.T. [Universitaetsklinikum Wuerzburg (Germany). Chirurgische Klinik I

    2012-07-15

    Background: The purpose of this work was to perform a single institution comparison between preoperative short-course radiotherapy (SC-RT) and long-course radiochemotherapy (LC-RCHT) for locally advanced rectal cancer. Methods: A total of 225 patients with clinical stage UICC II-III rectal cancer were treated with SC-RT (29 Gy in 10 twice daily fractions followed by immediate surgery; n = 108) or LC-RCHT (54 Gy in 28 fractions with simultaneous 5-fluorouracil (5-FU) {+-} oxaliplatin chemotherapy followed by delayed surgery; n = 117). All patients in the LC-RCHT cohort and patients in the SC-RT with pathological UICC stage {>=} II received adjuvant chemotherapy. Before 2004, the standard of care was SC-RT with LC-RCHT reserved for patients where downstaging was considered as required for sphincter preservation or curative resection. In the later period, SC-RT was practiced only for patients unfit for radiochemotherapy. Results: Patients in the LC-RCHT cohort had a significantly higher proportion of cT4 tumors, clinical node positivity, and lower tumor location. The 5-year local control (LC) and overall survival (OS) were 91% and 66% without differences between the SC-RT and LC-RCHT groups. Acute toxicity was increased during LC-RCHT (grade {>=} II 1% vs. 33%) and there were no differences in postoperative complications. Severe late toxicity grade {>=} III was increased after SC-RT (12% vs. 3%). Of patients aged > 80 years, 7 of 7 patients and 4 of 9 patients received curative surgery after SC-RT and LC-RCHT, respectively. Conclusion: Despite the fact that patients with worse prognostic factors were treated with LC-RCHT, there were no significant differences in LC and OS between the SC-RT and LC-RCHT group. Age > 80 years was identified as a significant risk factor for LC-RCHT and these patients could be treated preferably with SC-RT. (orig.)

  1. Nutritional predictors for postoperative short-term and long-term outcomes of patients with gastric cancer.

    Science.gov (United States)

    Kanda, Mitsuro; Mizuno, Akira; Tanaka, Chie; Kobayashi, Daisuke; Fujiwara, Michitaka; Iwata, Naoki; Hayashi, Masamichi; Yamada, Suguru; Nakayama, Goro; Fujii, Tsutomu; Sugimoto, Hiroyuki; Koike, Masahiko; Takami, Hideki; Niwa, Yukiko; Murotani, Kenta; Kodera, Yasuhiro

    2016-06-01

    Evidence indicates that impaired immunocompetence and nutritional status adversely affect short-term and long-term outcomes of patients with cancer. We aimed to evaluate the clinical significance of preoperative immunocompetence and nutritional status according to Onodera's prognostic nutrition index (PNI) among patients who underwent curative gastrectomy for gastric cancer (GC).This study included 260 patients with stage II/III GC who underwent R0 resection. The predictive values of preoperative nutritional status for postoperative outcome (morbidity and prognosis) were evaluated. Onodera's PNI was calculated as follows: 10 × serum albumin (g/dL) + 0.005 × lymphocyte count (per mm).The mean preoperative PNI was 47.8. The area under the curve for predicting complications was greater for PNI compared with the serum albumin concentration or lymphocyte count. Multivariate analysis identified preoperative PNI < 47 as an independent predictor of postoperative morbidity. Moreover, patients in the PNI < 47 group experienced significantly shorter overall and disease-free survival compared with those in the PNI ≥ 47 group, notably because of a higher prevalence of hematogenous metastasis as the initial recurrence. Subgroup analysis according to disease stage and postoperative adjuvant treatment revealed that the prognostic significance of PNI was more apparent in patients with stage II GC and in those who received adjuvant chemotherapy.Preoperative PNI is easy and inexpensive to determine, and our findings indicate that PNI served as a significant predictor of postoperative morbidity, prognosis, and recurrence patterns of patients with stage II/III GC.

  2. Sphincter Preservation After Short-term Preoperative Radiotherapy for Low Rectal Cancer - Presentation of Own Data and a Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Bujko, Krzysztof; Nowacki, Marek P.; Oldzki, Janusz; Sopyo, Rafa; Skoczylas, Jerzy; Chwaliski, Maciej [The Maria Sklodowska-Curie Memorial Cancer Centre and Inst. of Oncology, Warsaw (Poland)

    2001-07-01

    This report is based on a series of 108 patients with clinically staged T2 (9), T3 (94) and T4 (5) rectal cancer treated with preoperative irradiation with 25 Gy, 5 Gy per fraction given for one week. In 77% of patients, the tumour was located within 7 cm of the anal verge and in 15% the anal canal was involved. Surgery was usually undertaken during the week after irradiation. For low tumours, total mesorectal excision was performed, and for middle and upper cancers, the whole circumference of the mesorectum was excised at least 2 cm below the lower pole of a tumour. Tumour was resected in 103 patients, and sphincter-preserving surgery was performed in 73% of them. In the subgroup where the tumour was located higher than 4 cm from the anal verge, sphincter-preserving surgery was performed in 95%. The follow-up period ranged from 10 to 49 months, with a median of 25 months. Local recurrences were observed in 4% of patients. Anorectal dysfunction caused impairment of social life in 40% of patients and 18% admitted that their quality of life was seriously affected - however, none of them stated that they would have preferred a colostomy. These preliminary data suggest that following high dose per fraction short-term preoperative radiotherapy a high rate of sphincter-preserving surgery can be reached, with acceptable anorectal function and an acceptable rate of local failure and late complications. The results of our own data and literature review indicate the need for a randomized clinical trial comparing high dose per fraction preoperative radiotherapy with immediate surgery with conventional preoperative radiochemotherapy with delayed surgery.

  3. Impact of late radiation effects on cancer survivor children: an integrative review

    Energy Technology Data Exchange (ETDEWEB)

    Coura, Cibeli Fernandes; Modesto, Patrícia Cláudia [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil); Coura, Cibeli Fernandes; Modesto, Patrícia Cláudia [Hospital Israelita Albert Einstein, São Paulo, SP (Brazil)

    2016-07-01

    We aimed to identify the late effects of radiation exposure in pediatric cancer survivors. An integrated literature review was performed in the databases MEDLINE and LILACS and SciELO. Included were articles in Portuguese and English, published over the past 10 years, using the following keywords: “neoplasias/neoplasms” AND “radioterapia/radiotherapy” AND “radiação/radiation”. After analysis, 14 articles - published in nine well-known journals - met the inclusion criteria. The publications were divided into two categories: “Late endocrine effects” and “Late non-endocrine effects”. Considering the increased survival rates in children who had cancer, the impact of late effects of exposure to radiation during radiological examinations for diagnosis and treatment was analyzed. Childhood cancer survivors were exposed to several late effects and should be early and regularly followed up, even when exposed to low radiation doses.

  4. Impact of late radiation effects on cancer survivor children: an integrative review

    Science.gov (United States)

    Coura, Cibeli Fernandes; Modesto, Patrícia Cláudia

    2016-01-01

    ABSTRACT We aimed to identify the late effects of radiation exposure in pediatric cancer survivors. An integrated literature review was performed in the databases MEDLINE and LILACS and SciELO. Included were articles in Portuguese and English, published over the past 10 years, using the following keywords: “neoplasias/neoplasms” AND “radioterapia/radiotherapy” AND “radiação/radiation”. After analysis, 14 articles - published in nine well-known journals - met the inclusion criteria. The publications were divided into two categories: “Late endocrine effects” and “Late non-endocrine effects”. Considering the increased survival rates in children who had cancer, the impact of late effects of exposure to radiation during radiological examinations for diagnosis and treatment was analyzed. Childhood cancer survivors were exposed to several late effects and should be early and regularly followed up, even when exposed to low radiation doses. PMID:26313432

  5. Integrated analysis of copy number variation and genome-wide expression profiling in colorectal cancer tissues.

    Science.gov (United States)

    Ali Hassan, Nur Zarina; Mokhtar, Norfilza Mohd; Kok Sin, Teow; Mohamed Rose, Isa; Sagap, Ismail; Harun, Roslan; Jamal, Rahman

    2014-01-01

    Integrative analyses of multiple genomic datasets for selected samples can provide better insight into the overall data and can enhance our knowledge of cancer. The objective of this study was to elucidate the association between copy number variation (CNV) and gene expression in colorectal cancer (CRC) samples and their corresponding non-cancerous tissues. Sixty-four paired CRC samples from the same patients were subjected to CNV profiling using the Illumina HumanOmni1-Quad assay, and validation was performed using multiplex ligation probe amplification method. Genome-wide expression profiling was performed on 15 paired samples from the same group of patients using the Affymetrix Human Gene 1.0 ST array. Significant genes obtained from both array results were then overlapped. To identify molecular pathways, the data were mapped to the KEGG database. Whole genome CNV analysis that compared primary tumor and non-cancerous epithelium revealed gains in 1638 genes and losses in 36 genes. Significant gains were mostly found in chromosome 20 at position 20q12 with a frequency of 45.31% in tumor samples. Examples of genes that were associated at this cytoband were PTPRT, EMILIN3 and CHD6. The highest number of losses was detected at chromosome 8, position 8p23.2 with 17.19% occurrence in all tumor samples. Among the genes found at this cytoband were CSMD1 and DLC1. Genome-wide expression profiling showed 709 genes to be up-regulated and 699 genes to be down-regulated in CRC compared to non-cancerous samples. Integration of these two datasets identified 56 overlapping genes, which were located in chromosomes 8, 20 and 22. MLPA confirmed that the CRC samples had the highest gains in chromosome 20 compared to the reference samples. Interpretation of the CNV data in the context of the transcriptome via integrative analyses may provide more in-depth knowledge of the genomic landscape of CRC.

  6. Integrated analysis of copy number variation and genome-wide expression profiling in colorectal cancer tissues.

    Directory of Open Access Journals (Sweden)

    Nur Zarina Ali Hassan

    Full Text Available Integrative analyses of multiple genomic datasets for selected samples can provide better insight into the overall data and can enhance our knowledge of cancer. The objective of this study was to elucidate the association between copy number variation (CNV and gene expression in colorectal cancer (CRC samples and their corresponding non-cancerous tissues. Sixty-four paired CRC samples from the same patients were subjected to CNV profiling using the Illumina HumanOmni1-Quad assay, and validation was performed using multiplex ligation probe amplification method. Genome-wide expression profiling was performed on 15 paired samples from the same group of patients using the Affymetrix Human Gene 1.0 ST array. Significant genes obtained from both array results were then overlapped. To identify molecular pathways, the data were mapped to the KEGG database. Whole genome CNV analysis that compared primary tumor and non-cancerous epithelium revealed gains in 1638 genes and losses in 36 genes. Significant gains were mostly found in chromosome 20 at position 20q12 with a frequency of 45.31% in tumor samples. Examples of genes that were associated at this cytoband were PTPRT, EMILIN3 and CHD6. The highest number of losses was detected at chromosome 8, position 8p23.2 with 17.19% occurrence in all tumor samples. Among the genes found at this cytoband were CSMD1 and DLC1. Genome-wide expression profiling showed 709 genes to be up-regulated and 699 genes to be down-regulated in CRC compared to non-cancerous samples. Integration of these two datasets identified 56 overlapping genes, which were located in chromosomes 8, 20 and 22. MLPA confirmed that the CRC samples had the highest gains in chromosome 20 compared to the reference samples. Interpretation of the CNV data in the context of the transcriptome via integrative analyses may provide more in-depth knowledge of the genomic landscape of CRC.

  7. Reconstruction of gene regulatory modules in cancer cell cycle by multi-source data integration.

    Directory of Open Access Journals (Sweden)

    Yuji Zhang

    Full Text Available BACKGROUND: Precise regulation of the cell cycle is crucial to the growth and development of all organisms. Understanding the regulatory mechanism of the cell cycle is crucial to unraveling many complicated diseases, most notably cancer. Multiple sources of biological data are available to study the dynamic interactions among many genes that are related to the cancer cell cycle. Integrating these informative and complementary data sources can help to infer a mutually consistent gene transcriptional regulatory network with strong similarity to the underlying gene regulatory relationships in cancer cells. RESULTS AND PRINCIPAL FINDINGS: We propose an integrative framework that infers gene regulatory modules from the cell cycle of cancer cells by incorporating multiple sources of biological data, including gene expression profiles, gene ontology, and molecular interaction. Among 846 human genes with putative roles in cell cycle regulation, we identified 46 transcription factors and 39 gene ontology groups. We reconstructed regulatory modules to infer the underlying regulatory relationships. Four regulatory network motifs were identified from the interaction network. The relationship between each transcription factor and predicted target gene groups was examined by training a recurrent neural network whose topology mimics the network motif(s to which the transcription factor was assigned. Inferred network motifs related to eight well-known cell cycle genes were confirmed by gene set enrichment analysis, binding site enrichment analysis, and comparison with previously published experimental results. CONCLUSIONS: We established a robust method that can accurately infer underlying relationships between a given transcription factor and its downstream target genes by integrating different layers of biological data. Our method could also be beneficial to biologists for predicting the components of regulatory modules in which any candidate gene is involved

  8. Effects of a Short-Term Dance Movement Therapy Program on Symptoms and Stress in Patients With Breast Cancer Undergoing Radiotherapy: A Randomized, Controlled, Single-Blind Trial

    OpenAIRE

    Luk, MY; Yip, PSF; Cheung, IKM; Fong, TCt; Ho, RTH

    2016-01-01

    Context: Integrated interventions with combined elements of body movement and psychotherapy on treatment-related symptoms in cancer patients are relatively scarce. Objectives: The aim of the present study is to investigate the effectiveness of dance movement therapy (DMT) on improving treatment-related symptoms in a randomized controlled trial. Methods: A total of 139 Chinese patients with breast cancer awaiting adjuvant radiotherapy were randomized to DMT or control group. The intervention i...

  9. Pancreatic Expression database: a generic model for the organization, integration and mining of complex cancer datasets

    Directory of Open Access Journals (Sweden)

    Lemoine Nicholas R

    2007-11-01

    Full Text Available Abstract Background Pancreatic cancer is the 5th leading cause of cancer death in both males and females. In recent years, a wealth of gene and protein expression studies have been published broadening our understanding of pancreatic cancer biology. Due to the explosive growth in publicly available data from multiple different sources it is becoming increasingly difficult for individual researchers to integrate these into their current research programmes. The Pancreatic Expression database, a generic web-based system, is aiming to close this gap by providing the research community with an open access tool, not only to mine currently available pancreatic cancer data sets but also to include their own data in the database. Description Currently, the database holds 32 datasets comprising 7636 gene expression measurements extracted from 20 different published gene or protein expression studies from various pancreatic cancer types, pancreatic precursor lesions (PanINs and chronic pancreatitis. The pancreatic data are stored in a data management system based on the BioMart technology alongside the human genome gene and protein annotations, sequence, homologue, SNP and antibody data. Interrogation of the database can be achieved through both a web-based query interface and through web services using combined criteria from pancreatic (disease stages, regulation, differential expression, expression, platform technology, publication and/or public data (antibodies, genomic region, gene-related accessions, ontology, expression patterns, multi-species comparisons, protein data, SNPs. Thus, our database enables connections between otherwise disparate data sources and allows relatively simple navigation between all data types and annotations. Conclusion The database structure and content provides a powerful and high-speed data-mining tool for cancer research. It can be used for target discovery i.e. of biomarkers from body fluids, identification and analysis

  10. Integrating precision cancer medicine into healthcare-policy, practice, and research challenges.

    Science.gov (United States)

    Bertier, Gabrielle; Carrot-Zhang, Jian; Ragoussis, Vassilis; Joly, Yann

    2016-10-24

    Precision medicine (PM) can be defined as a predictive, preventive, personalized, and participatory healthcare service delivery model. Recent developments in molecular biology and information technology make PM a reality today through the use of massive amounts of genetic, 'omics', clinical, environmental, and lifestyle data. With cancer being one of the most prominent public health threats in developed countries, both the research community and governments have been investing significant time, money, and efforts in precision cancer medicine (PCM). Although PCM research is extremely promising, a number of hurdles still remain on the road to an optimal integration of standardized and evidence-based use of PCM in healthcare systems. Indeed, PCM raises a number of technical, organizational, ethical, legal, social, and economic challenges that have to be taken into account in the development of an appropriate health policy framework. Here, we highlight some of the more salient issues regarding the standards needed for integration of PCM into healthcare systems, and we identify fields where more research is needed before policy can be implemented. Key challenges include, but are not limited to, the creation of new standards for the collection, analysis, and sharing of samples and data from cancer patients, and the creation of new clinical trial designs with renewed endpoints. We believe that these issues need to be addressed as a matter of priority by public health policymakers in the coming years for a better integration of PCM into healthcare.

  11. Integrated exon level expression analysis of driver genes explain their role in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Mohammad Azhar Aziz

    Full Text Available Integrated analysis of genomic and transcriptomic level changes holds promise for a better understanding of colorectal cancer (CRC biology. There is a pertinent need to explain the functional effect of genome level changes by integrating the information at the transcript level. Using high resolution cytogenetics array, we had earlier identified driver genes by 'Genomic Identification of Significant Targets In Cancer (GISTIC' analysis of paired tumour-normal samples from colorectal cancer patients. In this study, we analyze these driver genes at three levels using exon array data--gene, exon and network. Gene level analysis revealed a small subset to experience differential expression. These results were reinforced by carrying out separate differential expression analyses (SAM and LIMMA. ATP8B1 was found to be the novel gene associated with CRC that shows changes at cytogenetic, gene and exon levels. Splice index of 29 exons corresponding to 13 genes was found to be significantly altered in tumour samples. Driver genes were used to construct regulatory networks for tumour and normal groups. There were rearrangements in transcription factor genes suggesting the presence of regulatory switching. The regulatory pattern of AHR gene was found to have the most significant alteration. Our results integrate data with focus on driver genes resulting in highly enriched novel molecules that need further studies to establish their role in CRC.

  12. A framework for organizing cancer-related variations from existing databases, publications and NGS data using a High-performance Integrated Virtual Environment (HIVE).

    Science.gov (United States)

    Wu, Tsung-Jung; Shamsaddini, Amirhossein; Pan, Yang; Smith, Krista; Crichton, Daniel J; Simonyan, Vahan; Mazumder, Raja

    2014-01-01

    Years of sequence feature curation by UniProtKB/Swiss-Prot, PIR-PSD, NCBI-CDD, RefSeq and other database biocurators has led to a rich repository of information on functional sites of genes and proteins. This information along with variation-related annotation can be used to scan human short sequence reads from next-generation sequencing (NGS) pipelines for presence of non-synonymous single-nucleotide variations (nsSNVs) that affect functional sites. This and similar workflows are becoming more important because thousands of NGS data sets are being made available through projects such as The Cancer Genome Atlas (TCGA), and researchers want to evaluate their biomarkers in genomic data. BioMuta, an integrated sequence feature database, provides a framework for automated and manual curation and integration of cancer-related sequence features so that they can be used in NGS analysis pipelines. Sequence feature information in BioMuta is collected from the Catalogue of Somatic Mutations in Cancer (COSMIC), ClinVar, UniProtKB and through biocuration of information available from publications. Additionally, nsSNVs identified through automated analysis of NGS data from TCGA are also included in the database. Because of the petabytes of data and information present in NGS primary repositories, a platform HIVE (High-performance Integrated Virtual Environment) for storing, analyzing, computing and curating NGS data and associated metadata has been developed. Using HIVE, 31 979 nsSNVs were identified in TCGA-derived NGS data from breast cancer patients. All variations identified through this process are stored in a Curated Short Read archive, and the nsSNVs from the tumor samples are included in BioMuta. Currently, BioMuta has 26 cancer types with 13 896 small-scale and 308 986 large-scale study-derived variations. Integration of variation data allows identifications of novel or common nsSNVs that can be prioritized in validation studies. Database URL: BioMuta: http

  13. Integrative review of the supportive care needs of Arab people affected by cancer

    Directory of Open Access Journals (Sweden)

    Ibrahim Alananzeh

    2016-01-01

    Full Text Available This review aimed to identify the unmet supportive care needs to conduct an integrative review of the literature, to identify the unmet supportive care needs of Arab people affected by cancer (patients and caregivers, and the impact of these needs on quality of life and psychosocial well-being. In July 2015 databases, search engines and electronic list servers were searched, with no limit on the year of publication. Reference lists of included articles and published reviews were also hand searched. Six studies met the inclusion criteria. Most studies examined the supportive care/unmet needs of Arab cancer patients and their family caregivers. Language, communication, information, and the need to get relief from dependency were the most frequently reported unmet needs among Arab cancer patients. For immigrant Arab patients, physical unmet needs were higher than other migrant groups and native Anglo-Australians. Arab caregivers' unmet needs included concerns about providing suitable care for their family member, sharing their experience with other caregivers, obtaining information, and, in the case of pediatric cancers, dealing with siblings' emotional reactions. The existing literature exploring the unmet supportive care needs of Arab people affected by cancer is limited suggesting that comprehensive studies are needed to enhance our understanding of these needs and to inform service planning.

  14. Integrating cervical cancer screening with HIV care in a district hospital in Abuja, Nigeria

    Directory of Open Access Journals (Sweden)

    Solomon Odafe

    2013-01-01

    Full Text Available Background: Human immunodeficiency virus positive (HIV+ women have a higher risk of developing invasive cervical cancer compared with uninfected women. This study aims to document programmatic experience of integrating cervical cancer screening using Visual Inspection and Acetic Acid (VIA into HIV care as well as to describe patients′ characteristics associated with positive VIA findings amongst HIV+ women. Materials and Methods: A cross-sectional study analysed routine service data collected at the antiretroviral therapy (ART and cervical cancer screening services. Our program integrated screening for cervical cancer using VIA technique to HIV care and treatment services through a combination of stakeholder engagement, capacity building for health workers, creating a bi-directional referral between HIV and reproductive health (RH services and provider initiated counselling and screening for cervical cancer. Information on patients′ baseline and clinical characteristics were captured using an electronic medical records system and then exported to Statistical Package for the Social Sciences (SPSS. Logistic regression model was used to estimate factors that influence VIA results. Results: A total of 834 HIV+ women were offered VIA screening between April 2010 and April 2011, and 805 (96.5% accepted it. Complete data was available for 802 (96.2% women. The mean age at screening and first sexual contact were 32.0 (SD 6.6 and 18.8 (SD 3.5 years, respectively. VIA was positive in 52 (6.5% women while 199 (24.8% had a sexually transmitted infection (STI. Of the 199 who had a STI, eight (4.0% had genital ulcer syndrome, 30 (15.1% had lower abdominal pain syndrome and 161 (80.9% had vaginal discharge syndrome. Presence of lower abdominal pain syndrome was found to be a significant predictor of a positive VIA result ( P = 0.001. Women with lower abdominal pain syndrome appeared to be more likely (OR 47.9, 95% CI: 4.8-480.4, P = 0.001 to have a

  15. Integrative Genomic Data Mining for Discovery of Potential Blood-Borne Biomarkers for Early Diagnosis of Cancer

    OpenAIRE

    Yongliang Yang; Pavel Pospisil; Iyer, Lakshmanan K.; S. James Adelstein; Amin I. Kassis

    2008-01-01

    BACKGROUND: With the arrival of the postgenomic era, there is increasing interest in the discovery of biomarkers for the accurate diagnosis, prognosis, and early detection of cancer. Blood-borne cancer markers are favored by clinicians, because blood samples can be obtained and analyzed with relative ease. We have used a combined mining strategy based on an integrated cancer microarray platform, Oncomine, and the biomarker module of the Ingenuity Pathways Analysis (IPA) program to identify po...

  16. Enhancing Psychosocial Outcomes for Young Adult Childhood CNS Cancer Survivors: Importance of Addressing Vocational Identity and Community Integration

    Science.gov (United States)

    Strauser, David R.; Wagner, Stacia; Wong, Alex W. K.

    2012-01-01

    The purpose of this study was to examine the relationship between vocational identity, community integration, positive and negative affect, and satisfaction with life in a group of young adult central nervous system (CNS) cancer survivors. Participants in this study included 45 young adult CNS cancer survivors who ranged in age from 18 to 30 years…

  17. Integrative Analysis of Gene Expression Data Including an Assessment of Pathway Enrichment for Predicting Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Pingzhao Hu

    2006-01-01

    Full Text Available Background: Microarray technology has been previously used to identify genes that are differentially expressed between tumour and normal samples in a single study, as well as in syntheses involving multiple studies. When integrating results from several Affymetrix microarray datasets, previous studies summarized probeset-level data, which may potentially lead to a loss of information available at the probe-level. In this paper, we present an approach for integrating results across studies while taking probe-level data into account. Additionally, we follow a new direction in the analysis of microarray expression data, namely to focus on the variation of expression phenotypes in predefined gene sets, such as pathways. This targeted approach can be helpful for revealing information that is not easily visible from the changes in the individual genes. Results: We used a recently developed method to integrate Affymetrix expression data across studies. The idea is based on a probe-level based test statistic developed for testing for differentially expressed genes in individual studies. We incorporated this test statistic into a classic random-effects model for integrating data across studies. Subsequently, we used a gene set enrichment test to evaluate the significance of enriched biological pathways in the differentially expressed genes identified from the integrative analysis. We compared statistical and biological significance of the prognostic gene expression signatures and pathways identified in the probe-level model (PLM with those in the probeset-level model (PSLM. Our integrative analysis of Affymetrix microarray data from 110 prostate cancer samples obtained from three studies reveals thousands of genes significantly correlated with tumour cell differentiation. The bioinformatics analysis, mapping these genes to the publicly available KEGG database, reveals evidence that tumour cell differentiation is significantly associated with many

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

    Directory of Open Access Journals (Sweden)

    Matthew Ruffalo

    2015-12-01

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

  19. Identification of diagnostic markers in colorectal cancer via integrative epigenomics and genomics data.

    Science.gov (United States)

    Kok-Sin, Teow; Mokhtar, Norfilza Mohd; Ali Hassan, Nur Zarina; Sagap, Ismail; Mohamed Rose, Isa; Harun, Roslan; Jamal, Rahman

    2015-07-01

    Apart from genetic mutations, epigenetic alteration is a common phenomenon that contributes to neoplastic transformation in colorectal cancer. Transcriptional silencing of tumor-suppressor genes without changes in the DNA sequence is explained by the existence of promoter hypermethylation. To test this hypothesis, we integrated the epigenome and transcriptome data from a similar set of colorectal tissue samples. Methylation profiling was performed using the Illumina InfiniumHumanMethylation27 BeadChip on 55 paired cancer and adjacent normal epithelial cells. Fifteen of the 55 paired tissues were used for gene expression profiling using the Affymetrix GeneChip Human Gene 1.0 ST array. Validation was carried out on 150 colorectal tissues using the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) technique. PCA and supervised hierarchical clustering in the two microarray datasets showed good separation between cancer and normal samples. Significant genes from the two analyses were obtained based on a ≥2-fold change and a false discovery rate (FDR) p-value of <0.05. We identified 1,081 differentially hypermethylated CpG sites and 36 hypomethylated CpG sites. We also found 709 upregulated and 699 downregulated genes from the gene expression profiling. A comparison of the two datasets revealed 32 overlapping genes with 27 being hypermethylated with downregulated expression and 4 hypermethylated with upregulated expression. One gene was found to be hypomethylated and downregulated. The most enriched molecular pathway identified was cell adhesion molecules that involved 4 overlapped genes, JAM2, NCAM1, ITGA8 and CNTN1. In the present study, we successfully identified a group of genes that showed methylation and gene expression changes in well-defined colorectal cancer tissues with high purity. The integrated analysis gives additional insight regarding the regulation of colorectal cancer-associated genes and their underlying mechanisms that

  20. Fluorescent multiple staining and CASA system to assess boar sperm viability and membranes integrity in short and long-term extenders

    Directory of Open Access Journals (Sweden)

    F. Cremonesi

    2013-03-01

    Full Text Available The aim of this study was to assess the effect on boar spermatozoa quality of in vitro storage in short and long-term extenders by fluorescent multiple staining (FMS and computer assisted semen analyzer (CASA. Fresh ejaculates from three healthy, sexually mature boars were diluted with equal volumes of six short-term or three long-term commercial extenders and stored at 19°C for 6 days (short-term or 12 days (long-term. The integrity of spermatozoa membranes was analyzed by FMS using propidium iodide, 5,5’,6,6’-tetrachloro-1,1’,3,3’ tetraethylbenzimidazolyl-carbocyanine iodide (JC-1 and fluorescein isothiocyanate-conjugated peanut agglutinin (PNA. The results obtained from this staining were compared with spermatozoa motility assessed by CASA. Our study showed that the number of viable spermatozoa with non-reacted acrosomes and intact mitochondria was positively correlated with the rate of motile spermatozoa (r2>0.9 irrespective of the extender used. In all extenders the number of motile spermatozoa significantly decreased as preservation period increased (P<0.05. FMS test is a potent indicator of sperm motility because it analyses mitochondrial integrity independently from observable alterations in motility. The best performing extenders were BTS for short-term storage and TRI-x-Cell for long-term storage.

  1. Fluorescent multiple staining and CASA system to assess boar sperm viability and membranes integrity in short and long-term extenders.

    Science.gov (United States)

    Lange-Consiglio, A; Meucci, A; Cremonesi, F

    2013-01-01

    The aim of this study was to assess the effect on boar spermatozoa quality of in vitro storage in short and long-term extenders by fluorescent multiple staining (FMS) and computer assisted semen analyzer (CASA). Fresh ejaculates from three healthy, sexually mature boars were diluted with equal volumes of six short-term or three long-term commercial extenders and stored at 19°C for 6 days (short-term) or 12 days (long-term). The integrity of spermatozoa membranes was analyzed by FMS using propidium iodide, 5,5',6,6'-tetrachloro-1,1',3,3' tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) and fluorescein isothiocyanate-conjugated peanut agglutinin (PNA). The results obtained from this staining were compared with spermatozoa motility assessed by CASA. Our study showed that the number of viable spermatozoa with non-reacted acrosomes and intact mitochondria was positively correlated with the rate of motile spermatozoa (r(2)>0.9) irrespective of the extender used. In all extenders the number of motile spermatozoa significantly decreased as preservation period increased (P<0.05). FMS test is a potent indicator of sperm motility because it analyses mitochondrial integrity independently from observable alterations in motility. The best performing extenders were BTS for short-term storage and TRI-x-Cell for long-term storage.

  2. Effectiveness of integrative modalities for pain and anxiety in children and adolescents with cancer: a systematic review.

    Science.gov (United States)

    Thrane, Susan

    2013-01-01

    Throughout the trajectory of the cancer experience, children and adolescents will likely face pain and anxiety in a variety of circumstances. Integrative therapies may be used either alone or as an adjunct to standard analgesics. Children are often very receptive to integrative therapies such as music, art, guided imagery, massage, therapeutic play, distraction, and other modalities. The effect of integrative modalities on pain and anxiety in children with cancer has not been systematically examined across the entire cancer experience. An in-depth search of PubMed, CINAHL, MedLine, PsychInfo, and Web of Science, integrative medicine journals, and the reference lists of review articles using the search terms pain, anxiety, pediatric, child*, oncology, cancer, neoplasm, complementary, integrative, nonconventional, and unconventional yielded 164 articles. Of these, 25 warranted full-text review. Cohen's d calculations show medium (d = 0.70) to extremely large (8.57) effect sizes indicating that integrative interventions may be very effective for pain and anxiety in children undergoing cancer treatment. Integrative modalities warrant further study with larger sample sizes to better determine their effectiveness in this population.

  3. Short-term effects of supplementary feeding with enteral nutrition via jejunostomy catheter on post-gastrectomy gastric cancer patients

    Institute of Scientific and Technical Information of China (English)

    WU Quan; YU Jian-chun; KANG Wei-ming; MA Zhi-qiang

    2011-01-01

    Background Most gastric cancer patients who undergo gastrectomy develop malnutrition.It is,therefore,crucial to establish an effective means to provide nutrition for these patients.To perform home enteral nutrition (EN) to ensure adequate nutritional intake in gastric cancer patients,we placed a jejunostomy catheter during gastric surgery.Most patients showed improved nutritional status.Methods Twenty-nine inpatients at our hospital underwent radical gastrectomy and jejunostomy from December 2002 to December 2007 and were designated as the jejunostomy group,and 32 matched patients without a jejunostomy tube were designated as the tube-free group.The jejunostomy group was treated with EN from 72 hours to 3 months postoperatively.The tube-free group did not receive EN.Data including preoperative and postoperative body weight,body mass index (BMI),nutrition risk screening (NRS) score,Karnofsky performance score (KPS),and laboratory biochemical indicators were documented respectively and compared.Results Compared with preoperative week 1,both groups showed decreased body weight and BMI at 3 months postoperatively.The weight loss in the jejunostomy group ((7.1±3.3) kg) was significantly less than that in the tube-free group ((9.9±3.1) kg).Similarly,BMI decreased by (2.4+1.0) kg/m2 in the jejunostomy group,which was significantly less than in the tube-free group ((3.2±0.9) kg/m2).The number of patients with postoperative NRS ≥3 was decreased in the jejunostomy group,but was increased in the tube-free group,and this difference was significant.There were no significant differences between the two groups in total lymphocyte count,hemoglobin,albumin and prealbumin,and adverse drug effects.Conclusions Short-term (3 months) EN supplementation via jejunostomy tube can reduce the risk of malnutrition and weight loss,and improve tolerance of chemotherapy.Tube feeding is reliable for achieving these goals because it is not important whether or not the patients have appetites.

  4. Integrative Molecular Profiling Reveals Asparagine Synthetase Is a Target in Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Sircar, Kanishka; Huang, Heng; Hu, Limei; Cogdell, David; Dhillon, Jasreman; Tzelepi, Vassiliki; Efstathiou, Eleni; Koumakpayi, Ismaël H.; Saad, Fred; Luo, Dijun; Bismar, Tarek A.; Aparicio, Ana; Troncoso, Patricia; Navone, Nora; Zhang, Wei

    2013-01-01

    The identification of new and effective therapeutic targets for the lethal, castration-resistant stage of prostate cancer (CRPC) has been challenging because of both the paucity of adequate frozen tissues and a lack of integrated molecular analysis. Therefore, in this study, we performed a genome-wide analysis of DNA copy number alterations from 34 unique surgical CRPC specimens and 5 xenografts, with matched transcriptomic profiling of 25 specimens. An integrated analysis of these data revealed that the asparagine synthetase (ASNS) gene showed a gain in copy number and was overexpressed at the transcript level. The overexpression of ASNS was validated by analyzing other public CRPC data sets. ASNS protein expression, as detected by reverse-phase protein lysate array, was tightly correlated with gene copy number. In addition, ASNS protein expression, as determined by IHC analysis, was associated with progression to a therapy-resistant disease state in TMAs that included 77 castration-resistant and 40 untreated prostate cancer patient samples. Knockdown of ASNS by small-interfering RNAs in asparagine-deprived media led to growth inhibition in both androgen-responsive (ie, LNCaP) and castration-resistant (ie, C4-2B) prostate cancer cell lines and in cells isolated from a CRPC xenograft (ie, MDA PCa 180-30). Together, our results suggest that ASNS is up-regulated in cases of CRPC and that depletion of asparagine using ASNS inhibitors will be a novel strategy for targeting CRPC cells. PMID:22245216

  5. Internet-Based Interactive Support for Cancer Patients: Are Integrated Systems Better?

    Science.gov (United States)

    Gustafson, David H.; Hawkins, Robert; McTavish, Fiona; Pingree, Suzanne; Chen, Wei Chih; Volrathongchai, Kanittha; Stengle, William; Stewart, James A.; Serlin, Ronald C.

    2011-01-01

    To compare the benefits of the Internet generally versus a focused system of services, 257 breast cancer patients were randomly assigned to a control group, access to the Internet with links to high-quality breast cancer sites, or access to an eHealth system (Comprehensive Health Enhancement Support System, CHESS) that integrated information, support, and decision and analysis tools. The intervention lasted 5 months, and self-report data on quality of life, health-care competence, and social support were collected at pretest and at 2-, 4-, and 9-month posttests. CHESS subjects logged on more overall than Internet subjects and accessed more health resources, but the latter used non health-related sites more. Subjects with access to the Internet alone experienced no better outcomes than controls at any of the 3 time points, compared to pretest levels. Subjects with CHESS experienced greater social support during the intervention period and had higher scores on all 3 outcomes at 9 months, 4 months after the intervention ended. CHESS subjects also scored higher than those with Internet access during the intervention period but not significantly after the intervention ended. Thus, CHESS (with one simple interface and integrated information, communication, and skills services) helped newly diagnosed breast cancer patients even after computers were removed. In contrast, patients received little benefit from Internet access, despite having links to a variety of high-quality sites. PMID:21804645

  6. The short-term effects of an integrated care model for the frail elderly on health, quality of life, health care use and satisfaction with care

    Directory of Open Access Journals (Sweden)

    Wilhelmina Mijntje Looman

    2014-12-01

    Full Text Available Purpose: This study explores the short-term value of integrated care for the frail elderly by evaluating the effects of the Walcheren Integrated Care Model on health, quality of life, health care use and satisfaction with care after three months.Intervention: Frailty was preventively detected in elderly living at home with the Groningen Frailty Indicator. Geriatric nurse practitioners and secondary care geriatric nursing specialists were assigned as case managers and co-ordinated the care agreed upon in a multidisciplinary meeting. The general practitioner practice functions as a single entry point and supervises the co-ordination of care. The intervention encompasses task reassignment between nurses and doctors and consultations between primary, secondary and tertiary care providers. The entire process was supported by multidisciplinary protocols and web-based patient files.Methods: The design of this study was quasi-experimental. In this study, 205 frail elderly patients of three general practitioner practices that implemented the integrated care model were compared with 212 frail elderly patients of five general practitioner practices that provided usual care. The outcomes were assessed using questionnaires. Baseline measures were compared with a three-month follow-up by chi-square tests, t-tests and regression analysis.Results and conclusion: In the short term, the integrated care model had a significant effect on the attachment aspect of quality of life. The frail elderly patients were better able to obtain the love and friendship they desire. The use of care did not differ despite the preventive element and the need for assessments followed up with case management in the integrated care model. In the short term, there were no significant changes in health. As frailty is a progressive state, it is assumed that three months are too short to influence changes in health with integrated care models. A more longitudinal approach is required

  7. The short-term effects of an integrated care model for the frail elderly on health, quality of life, health care use and satisfaction with care

    Directory of Open Access Journals (Sweden)

    Wilhelmina Mijntje Looman

    2014-12-01

    Full Text Available Purpose: This study explores the short-term value of integrated care for the frail elderly by evaluating the effects of the Walcheren Integrated Care Model on health, quality of life, health care use and satisfaction with care after three months. Intervention: Frailty was preventively detected in elderly living at home with the Groningen Frailty Indicator. Geriatric nurse practitioners and secondary care geriatric nursing specialists were assigned as case managers and co-ordinated the care agreed upon in a multidisciplinary meeting. The general practitioner practice functions as a single entry point and supervises the co-ordination of care. The intervention encompasses task reassignment between nurses and doctors and consultations between primary, secondary and tertiary care providers. The entire process was supported by multidisciplinary protocols and web-based patient files. Methods: The design of this study was quasi-experimental. In this study, 205 frail elderly patients of three general practitioner practices that implemented the integrated care model were compared with 212 frail elderly patients of five general practitioner practices that provided usual care. The outcomes were assessed using questionnaires. Baseline measures were compared with a three-month follow-up by chi-square tests, t-tests and regression analysis. Results and conclusion: In the short term, the integrated care model had a significant effect on the attachment aspect of quality of life. The frail elderly patients were better able to obtain the love and friendship they desire. The use of care did not differ despite the preventive element and the need for assessments followed up with case management in the integrated care model. In the short term, there were no significant changes in health. As frailty is a progressive state, it is assumed that three months are too short to influence changes in health with integrated care models. A more longitudinal approach is

  8. Phase I study of short-time oxaliplatin, capecitabine and epirubicin (EXE) as first line therapy in patients with non-resectable gastric cancer

    DEFF Research Database (Denmark)

    Dupont, Jeanette; Jensen, Helle A; Jensen, Benny V

    2007-01-01

    A phase I trial of short-time oxaliplatin (E), capecitabine (X) and epirubicin (E) for patients with metastatic gastric cancer was initiated to establish the recommended dose for further therapy with short-time EXE. Patients received out-patient therapy with a fixed dose of epirubicin 50 mg/m2 day......-8), median survival was 9.2 months and median TTP was 7.5 months. A combination of epirubicin 50 mg/m2 day 1, capecitabine 1,000 mg/m2 continuously and oxaliplatin 130 mg/m2 day 1 each 3 weeks is an easily administered and well tolerated out-patient regimen for patients with non-resectable gastric cancer....

  9. Duration of short-course androgen suppression therapy and the risk of death as a result of prostate cancer.

    LENUS (Irish Health Repository)

    D'Amico, Anthony V

    2011-12-10

    We evaluated whether the duration of androgen suppression therapy (AST) had an impact on the risk of prostate cancer-specific mortality (PCSM) in men with unfavorable-risk prostate cancer (PC) within established Gleason score (GS) categories.

  10. Semantic Integration of Cervical Cancer Data Repositories to Facilitate Multicenter Association Studies: The ASSIST Approach

    Directory of Open Access Journals (Sweden)

    Theodoros Agorastos

    2009-02-01

    Full Text Available The current work addresses the unification of Electronic Health Records related to cervical cancer into a single medical knowledge source, in the context of the EU-funded ASSIST research project. The project aims to facilitate the research for cervical precancer and cancer through a system that virtually unifies multiple patient record repositories, physically located in different medical centers/hospitals, thus, increasing flexibility by allowing the formation of study groups “on demand” and by recycling patient records in new studies. To this end, ASSIST uses semantic technologies to translate all medical entities (such as patient examination results, history, habits, genetic profile and represent them in a common form, encoded in the ASSIST Cervical Cancer Ontology. The current paper presents the knowledge elicitation approach followed, towards the definition and representation of the disease’s medical concepts and rules that constitute the basis for the ASSIST Cervical Cancer Ontology. The proposed approach constitutes a paradigm for semantic integration of heterogeneous clinical data that may be applicable to other biomedical application domains.

  11. Multiplexed cancer biomarker detection using chip-integrated silicon photonic sensor arrays.

    Science.gov (United States)

    Washburn, Adam L; Shia, Winnie W; Lenkeit, Kimberly A; Lee, So-Hyun; Bailey, Ryan C

    2016-09-21

    The analysis of disease-specific biomarker panels holds promise for the early detection of a range of diseases, including cancer. Blood-based biomarkers, in particular, are attractive targets for minimally-invasive disease diagnosis. Specifically, a panel of organ-specific biomarkers could find utility as a general disease surveillance tool enabling earlier detection or prognostic monitoring. Using arrays of chip-integrated silicon photonic sensors, we describe the simultaneous detection of eight cancer biomarkers in serum in a relatively rapid (1 hour) and fully automated antibody-based sandwich assay. Biomarkers were chosen for their applicability to a range of organ-specific cancers, including disease of the pancreas, liver, ovary, breast, lung, colorectum, and prostate. Importantly, we demonstrate that selected patient samples reveal biomarker "fingerprints" that may be useful for a personalized cancer diagnosis. More generally, we show that the silicon photonic technology is capable of measuring multiplexed panels of protein biomarkers that may have broad utility in clinical diagnostics.

  12. Health-related quality of life among patients with advanced cancer: an integrative review

    Directory of Open Access Journals (Sweden)

    Maria Eliane Moreira Freire

    2014-04-01

    Full Text Available This integrative literature review aimed to characterize scientific articles on health-related quality of life – HRQoL – among patients with advanced cancer from national and international literature, and summarize those factors evidenced in the literature that contributed to the improvement or worsening of HRQoL among patients with advanced cancer. The search for materials was conducted in the following databases: CINAHL, EMBASE, PubMed, SciELO and LILACS. Among the 21 articles in the sample, 13 showed an improvement of HRQoL among patients with advanced cancer related to the development of physical, emotional and spiritual interventions. In eight studies, we identified predictive symptoms of low HRQoL, such as pain, fatigue, sleep disorders, depression, nutritional changes, and others. The results showed that clinical manifestations, which many times were inherent in cancer, such as factors that can lower patients’ HRQoL, while physical, psychological and spiritual benefits resulting from therapeutic interventions may promote its improvement.

  13. Recurrent integration of human papillomaviruses 16, 45, and 67 near translocation breakpoints in new cervical cancer cell lines

    NARCIS (Netherlands)

    Koopman, L A; Szuhai, K; van Eendenburg, J D; Bezrookove, V; Kenter, G G; Schuuring, E; Tanke, H; Fleuren, G J

    1999-01-01

    Progressive chromosomal changes and integration of human papillomavirus (HPV) sequences mark the development of invasive cervical cancer. Chromosomal localization of HPV integration is essential to the study of genomic regions involved in HPV-induced pathogenesis. Yet, the available information abou

  14. Strategies for integrated analysis of genetic, epigenetic and gene expression variation in cancer: addressing the challenges

    Directory of Open Access Journals (Sweden)

    Louise Bruun Thingholm

    2016-02-01

    Full Text Available The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis. However, integration of heterogeneous measurements of biological variation is a non-trivial exercise due to the diversity of the human genome and the variety of output data formats and genome coverage obtained from the commonly used molecular platforms. This review article will provide an introduction to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured – making the assessment of disease risk against a composite genomic factor possible. The focus of this review is to provide an overview and introduction to the main strategies and to discuss where there is a need for further development.

  15. Developing a service model that integrates palliative care throughout cancer care: the time is now.

    Science.gov (United States)

    Partridge, Ann H; Seah, Davinia S E; King, Tari; Leighl, Natasha B; Hauke, Ralph; Wollins, Dana S; Von Roenn, Jamie Hayden

    2014-10-10

    Palliative care is a fundamental component of cancer care. As part of the 2011 to 2012 Leadership Development Program (LDP) of the American Society of Clinical Oncology (ASCO), a group of participants was charged with advising ASCO on how to develop a service model integrating palliative care throughout the continuum of cancer care. This article presents the findings of the LDP group. The group focused on the process of palliative care delivery in the oncology setting. We identified key elements for models of palliative care in various settings to be potentially equitable, sustainable, feasible, and acceptable, and here we describe a dynamic model for the integrated, simultaneous implementation of palliative care into oncology practice. We also discuss critical considerations to better integrate palliative care into oncology, including raising consciousness and educating both providers and the public about the importance of palliative care; coordinating palliative care efforts through strengthening affiliations and/or developing new partnerships; prospectively evaluating the impact of palliative care on patient and provider satisfaction, quality improvement, and cost savings; and ensuring sustainability through adequate reimbursement and incentives, including linkage of performance data to quality indicators, and coordination with training efforts and maintenance of certification requirements for providers. In light of these findings, we believe the confluence of increasing importance of incorporation of palliative care education in oncology education, emphasis on value-based care, growing use of technology, and potential cost savings makes developing and incorporating palliative care into current service models a meaningful goal.

  16. Impact of tumour bed boost integration on acute and late toxicity in patients with breast cancer: A systematic review.

    Science.gov (United States)

    Hamilton, Daniel George; Bale, Rebecca; Jones, Claire; Fitzgerald, Emma; Khor, Richard; Knight, Kellie; Wasiak, Jason

    2016-06-01

    The purpose of this systematic review was to summarise the evidence from studies investigating the integration of tumour bed boosts into whole breast irradiation for patients with Stage 0-III breast cancer, with a focus on its impact on acute and late toxicities. A comprehensive systematic electronic search through the Ovid MEDLINE, EMBASE and PubMed databases from January 2000 to January 2015 was conducted. Studies were considered eligible if they investigated the efficacy of hypo- or normofractionated whole breast irradiation with the inclusion of a daily concurrent boost. The primary outcomes of interest were the degree of observed acute and late toxicity following radiotherapy treatment. Methodological quality assessment was performed on all included studies using either the Newcastle-Ottawa Scale or a previously published investigator-derived quality instrument. The search identified 35 articles, of which 17 satisfied our eligibility criteria. Thirteen and eleven studies reported on acute and late toxicities respectively. Grade 3 acute skin toxicity ranged from 1 to 7% whilst moderate to severe fibrosis and telangiectasia were both limited to 9%. Reported toxicity profiles were comparable to historical data at similar time-points. Studies investigating the delivery of concurrent boosts with whole breast radiotherapy courses report safe short to medium-term toxicity profiles and cosmesis rates. Whilst the quality of evidence and length of follow-up supporting these findings is low, sufficient evidence has been generated to consider concurrent boost techniques as an alternative to conventional sequential techniques.

  17. A Total Integrated Biochip System for Detection of SNP in Cancer

    DEFF Research Database (Denmark)

    Perch-Nielsen, Ivan R.; Brivio, Monica; Schaeffer, Eva

    2010-01-01

    and treatment. In this paper, we described a total integrated BIOLABCHIP namely SMART-BioMEMS for rapid detection and identification SNPs of Kirsten-RAS (K-ras) and TP53 genes in cancer. The SMART-BioMEMS system consist of different components: An optical readout system, disposable biochip; and a reusable...... mutation is a hallmark of many tumors. Importantly, most anticancer agents act by inducing apoptosis and, typically, p53- deficient tumors are more resistant to drug-induced apoptosis than those carrying wild-type p53. It is therefore important to analyze such SNPs and point mutation in cancer diagnosis...... actuators chip that can perform all the steps from sample preparation, DNA isolation and purification, PCR amplification, Enzymatic clean up, mini-sequencing and SNP detection. The prototype of the SmartBIOMEMS system designs, detail of different components and functions will be present and discusses...

  18. Noninvasive photothermal cancer therapy nanoplatforms via integrating nanomaterials and functional polymers.

    Science.gov (United States)

    Ban, Qingfu; Bai, Ting; Duan, Xiao; Kong, Jie

    2017-01-31

    In the cutting-edge field of cancer therapy, noninvasive photothermal therapy (PTT) has received great attention because it is considered to overcome the drawbacks of conventional surgery, radiotherapy and chemotherapy of severe body injuries and side effects on the immune system. The construction of PTT therapeutic and theranostic nanoplatforms is the key issue in achieving tumor targeting, imaging and therapy in a synergetic manner. In this review, we focus on the recent advances in constructing PTT therapeutic and theranostic nanoplatforms by integrating nanomaterials and functional polymers. The noninvasive photothermal cancer therapy mechanism and achievement strategies of PTT therapeutic and theranostic nanoplatforms are presented as well as the innovative construction strategies and perspectives for the future. Owing to their high tumor ablation efficiency, biological availability and low- or non-toxicity, PTT therapeutic and theranostic nanoplatforms are promising and emerging in medicine and clinical applications.

  19. Retracted: Identification of Novel Biomarkers for Pancreatic Cancer Using Integrated Transcriptomics With Functional Pathways Analysis.

    Science.gov (United States)

    Zhang, Xuan; Tong, Pan; Chen, Jinyun; Pei, Zenglin; Zhang, Xiaoyan; Chen, Weiping; Xu, Jianqing; Wang, Jin

    2016-02-22

    Retraction: 'Identification of Novel Biomarkers for Pancreatic Cancer Using Integrated Transcriptomics With Functional Pathways Analysis' by Zhang, X., Tong, P., Chen, J., Pei, Z., Zhang, X., Chen, W., Xu, J. and Wang, J. The above article from the Journal of Cellular Physiology, published online on 10 March 2016 in Wiley Online Library as Early View (http://onlinelibrary.wiley.com/enhanced/doi/10.1002/jcp.25353/), has been retracted by agreement between Gary Stein, the journal's Editor-in-Chief, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation at the University of Texas, MD Anderson Cancer Center, which confirmed that the article was submitted and approved for publication by Dr. Jin Wang without acknowledgement of NIH funding received or the consent and authorship of Dr. Ann Killary and Dr. Subrata Sen, with whom the manuscript was originally drafted.

  20. Integrated extracellular matrix signaling in mammary gland development and breast cancer progression.

    Science.gov (United States)

    Zhu, Jieqing; Xiong, Gaofeng; Trinkle, Christine; Xu, Ren

    2014-09-01

    Extracellular matrix (ECM), a major component of the cellular microenvironment, plays critical roles in normal tissue morphogenesis and disease progression. Binding of ECM to membrane receptor proteins, such as integrin, discoidin domain receptors, and dystroglycan, elicits biochemical and biomechanical signals that control cellular architecture and gene expression. These ECM signals cooperate with growth factors and hormones to regulate cell migration, differentiation, and transformation. ECM signaling is tightly regulated during normal mammary gland development. Deposition and alignment of fibrillar collagens direct migration and invasion of mammary epithelial cells during branching morphogenesis. Basement membrane proteins are required for polarized acinar morphogenesis and milk protein expression. Deregulation of ECM proteins in the long run is sufficient to promote breast cancer development and progression. Recent studies demonstrate that the integrated biophysical and biochemical signals from ECM and soluble factors are crucial for normal mammary gland development as well as breast cancer progression.

  1. [Nursing in palliative care to children and adolescents with cancer: integrative literature review].

    Science.gov (United States)

    da Costa, Thailly Faria; Ceolim, Maria Filomena

    2010-12-01

    Pediatric palliative care is a challenge for nursing because it requires emotional balance and knowledge about its specific features. This study is an integrative literature review that aims to identify nursing actions in palliative care for children and adolescents with cancer, considering peculiarities of the disease and dying process. The review was performed by searching for articles indexed in Biblioteca Virtual da Adolescência (Adolec), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and PubMed databases from January 2004 till May 2009. From 29 references found, six met inclusion criteria. Results show teamwork, home care, pain management, dialogue, family support and particularities of childhood cancer fundamental tools for nursing in palliative care. The complexity of care in this situation requires solidarity, compassion, support and relieving suffering.

  2. An Integrative Pathway-based Clinical-genomic Model for Cancer Survival Prediction.

    Science.gov (United States)

    Chen, Xi; Wang, Lily; Ishwaran, Hemant

    2010-09-01

    Prediction models that use gene expression levels are now being proposed for personalized treatment of cancer, but building accurate models that are easy to interpret remains a challenge. In this paper, we describe an integrative clinical-genomic approach that combines both genomic pathway and clinical information. First, we summarize information from genes in each pathway using Supervised Principal Components (SPCA) to obtain pathway-based genomic predictors. Next, we build a prediction model based on clinical variables and pathway-based genomic predictors using Random Survival Forests (RSF). Our rationale for this two-stage procedure is that the underlying disease process may be influenced by environmental exposure (measured by clinical variables) and perturbations in different pathways (measured by pathway-based genomic variables), as well as their interactions. Using two cancer microarray datasets, we show that the pathway-based clinical-genomic model outperforms gene-based clinical-genomic models, with improved prediction accuracy and interpretability.

  3. Modeling short-term variability of semivolatile organic chemicals in air at a local scale: an integrated modeling approach.

    Science.gov (United States)

    Morselli, Melissa; Ghirardello, Davide; Semplice, Matteo; Di Guardo, Antonio

    2011-05-01

    Monitoring campaigns from different locations have recently shown how air concentrations of persistent semivolatile contaminants such as polychlorinated biphenyls (PCBs) often exhibit short-term (less than 24 h) variations. The observed patterns have been ascribed to different factors, such as temperature-mediated air-surface exchange and variability of planetary boundary layer (PBL) height and dynamics. Here, we present a new modeling approach developed in order to investigate the short-term variability in air concentrations of organic pollutants at a local scale. A new dynamic multimedia box model is supplied by a meteorological preprocessor (AERMET) with hourly values of air compartment height and wind speed. The resulting model is tested against an existing dataset of PCB air concentrations measured in Zurich, Switzerland. Results show the importance of such modeling approach in elucidating the short- and long-term behavior of semivolatile contaminants in the air/soil system.

  4. Total laparoscopic right hemicolectomy with 3-step stapled intracorporeal isoperistaltic ileocolic anastomosis for colon cancer: An evaluation of short-term outcomes.

    Science.gov (United States)

    Jian-Cheng, Tu; Shu-Sheng, Wang; Bo, Zhang; Jian, Fang; Liang, Zhou

    2016-11-01

    Laparoscopic right hemicolectomy with extracorporeal anastomosis is a widely used procedure; several authors have published their approach to intracorporeal anastomosis. In this paper, we present an approach developed by us and compare short-term outcomes with those of extracorporeal anastomosis in colon cancer patients.Retrospective review of colon cancer patients treated with laparoscopic right hemicolectomy either with intracorporeal anastomosis (TLG group) or extracorporeal anastomosis (LG group) at the Zhangjiagang Hospital Affiliated to Soochow University between January 2011 and October 2015. Operative and postoperative data are compared.Around 85 patients underwent laparoscopic hemicolectomy (56 TLG and 29 LG) during the reference period for this study. Age, gender, body mass index (BMI), stage of cancer, operation time, number of lymph nodes harvested, and length of hospital stay were comparable between the 2 groups. In the TLG group, the ileocolic anastomosis time was significantly shorter (9.9-15.5 minutes vs 13.5-18.2 minutes in LG; P anastomosis for colon cancer is a safe and reliable procedure. Its advantages include short anastomosis time, less intraoperative blood loss, less postoperative pain, and early bowel function recovery.

  5. Integrating Palliative Care in Pediatric Oncology: An Evolving Paradigm for Comprehensive Cancer Care

    Science.gov (United States)

    Levine, Deena R.; Johnson, Liza-Marie; Snyder, Angela; Wiser, Robert K.; Gibson, Deborah; Kane, Javier R.; Baker, Justin N.

    2017-01-01

    Background The demonstrated benefit of integrating palliative care (PC) into cancer treatment has triggered an increased need for PC services. The trajectory of integrating PC in comprehensive cancer centers, particularly pediatric centers, is unknown. We describe our eight-year experience of initiating and establishing PC with the Quality of Life Service (QoLS) at St. Jude Children’s Research Hospital. Patients and Methods We retrospectively reviewed records of patients seen by the QoLS (n= 615) from March 2007 to December 2014. Variables analyzed for each year, using descriptive statistics, included diagnostic groups, QoLS encounters, goals of care, duration of survival, and location of death. Results Total QoLS patient encounters increased from 58 (2007) to 1297 (2014), new consults increased from 17 (2007) to 115 (2014), and mean encounters per patient increased from 5.06 (2007) to 16.11 (2014). Goal of care at initial consultation shifted from primarily comfort to an increasing goal of cure. The median number of days from initial consult to death increased from 52 days (2008) to 223 days (2014). A trend toward increased outpatient location of death was noted with 42% outpatient deaths in 2007 increasing to a majority in each subsequent year (range 51–74%). Hospital-wide, patients receiving PC services before death increased from approximately 50% to nearly 100%. Conclusions Since its inception, the QoLS experienced a dramatic rise in referrals and encounters per patient, utilization by all clinical services, a trend toward earlier consultation and longer term follow-up, increasing outpatient location of death, and near-universal PC involvement at the end-of-life. The successful integration of PC in a comprehensive cancer center, and resulting potential for improved care provision over time, can serve as a model for other programs on a broad scale. PMID:27283167

  6. Problematic integration theory: implications of supportive communication for breast cancer patients.

    Science.gov (United States)

    Repass, Michael; Matusitz, Jonathan

    2010-05-01

    In this analysis, the authors apply Problematic Integration (PI) Theory to the way breast cancer patients engage in and receive support. The theory focuses on the relationship between expectations and desires, and enlightens cognitive and communicative responses to situations that involve tensions between their perceived likelihoods of occurrence and their perceived values. The relationship between PI Theory and its significance in treating and providing support for patients suffering from terminal illnesses is one of great interest to health care providers and those charged with creating supportive messages and support groups for those patients.

  7. The impact of supervised exercise intervention on short-term postprogram leisure time physical activity level in cancer patients undergoing chemotherapy: 1- and 3-month follow-up on the body & cancer project

    DEFF Research Database (Denmark)

    Klausen, Julie Midtgaard; Tveterås, Anders; Rørth, Mikael Rahbek

    2006-01-01

    BACKGROUND: Exercise is becoming an important component of cancer rehabilitation programs. A consistent finding across studies is that patients experience improved physical fitness and reduced fatigue. However, sustained physical activity is essential if the benefits are to be preserved over...... the course of cancer survivorship. OBJECTIVE: This study examined self-reported short-term exercise adherence following a 6-week, supervised exercise program (muscle strength, cardiovascular fitness, relaxation, body awareness, and massage) in a heterogeneous group of 61 cancer patients (mean age 42.9 years......, and postprogram changes in depression. SIGNIFICANCE OF RESEARCH: Given the significant decrease in postprogram PA level, especially in subjects still undergoing cancer treatment, the study suggests that continuous supervised programs may be required in order to encourage and support exercise adherence...

  8. Identifying and assessing the risk of opioid abuse in patients with cancer: an integrative review

    Directory of Open Access Journals (Sweden)

    Carmichael AN

    2016-06-01

    Full Text Available Ashley-Nicole Carmichael,1 Laura Morgan,1 Egidio Del Fabbro2 1School of Pharmacy, 2Division of Hematology, Oncology, and Palliative Care, Virginia Commonwealth University, Richmond, VA, USA Background: The misuse and abuse of opioid medications in many developed nations is a health crisis, leading to increased health-system utilization, emergency department visits, and overdose deaths. There are also increasing concerns about opioid abuse and diversion in patients with cancer, even at the end of life. Aims: To evaluate the current literature on opioid misuse and abuse, and more specifically the identification and assessment of opioid-abuse risk in patients with cancer. Our secondary aim is to offer the most current evidence of best clinical practice and suggest future directions for research. Materials and methods: Our integrative review included a literature search using the key terms “identification and assessment of opioid abuse in cancer”, “advanced cancer and opioid abuse”, “hospice and opioid abuse”, and “palliative care and opioid abuse”. PubMed, PsycInfo, and Embase were supplemented by a manual search. Results: We found 691 articles and eliminated 657, because they were predominantly noncancer populations or specifically excluded cancer patients. A total of 34 articles met our criteria, including case studies, case series, retrospective observational studies, and narrative reviews. The studies were categorized into screening questionnaires for opioid abuse or alcohol, urine drug screens to identify opioid misuse or abuse, prescription drug-monitoring programs, and the use of universal precautions. Conclusion: Screening questionnaires and urine drug screens indicated at least one in five patients with cancer may be at risk of opioid-use disorder. Several studies demonstrated associations between high-risk patients and clinical outcomes, such as aberrant behavior, prolonged opioid use, higher morphine-equivalent daily dose

  9. An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state.

    Science.gov (United States)

    Polytarchou, Christos; Iliopoulos, Dimitrios; Struhl, Kevin

    2012-09-01

    Cancer stem-like cells (CSCs) are a highly tumorigenic cell type present as a minority population in developmentally diverse tumors and cell lines. Using a genetic screen in an inducible model of CSC formation in a breast cell line, we identify microRNAs (miRNAs) that inhibit CSC growth and are down-regulated in CSCs. Aside from the previously identified miR-200 family, these include the miR-15/16 (miR-16, miR-15b) and miR-103/107 (miR-103, miR-107) families as well as miR-145, miR-335, and miR-128b. Interestingly, these miRNAs affect common target genes that encode the Bmi1 and Suz12 components of the polycomb repressor complexes as well as the DNA-binding transcription factors Zeb1, Zeb2, and Klf4. Conversely, expression of the CSC-modulating miRNAs is inhibited by Zeb1 and Zeb2. There is an inverse relationship between the levels of CSC-regulating miRNAs and their respective targets in samples from triple-negative breast cancer patients, providing evidence for the relevance of these interactions in human cancer. In addition, combinatorial overexpression of these miRNAs progressively attenuates the growth of CSCs derived from triple-negative breast cancers. These observations suggest that CSC formation and function are reinforced by an integrated regulatory circuit of miRNAs, transcription factors, and chromatin-modifying activities that can act as a bistable switch to drive cells into either the CSC or the nonstem state within the population of cancer cells.

  10. An integrated transcriptional regulatory circuit that reinforces the breast cancer stem cell state

    Science.gov (United States)

    Polytarchou, Christos; Iliopoulos, Dimitrios; Struhl, Kevin

    2012-01-01

    Cancer stem-like cells (CSCs) are a highly tumorigenic cell type present as a minority population in developmentally diverse tumors and cell lines. Using a genetic screen in an inducible model of CSC formation in a breast cell line, we identify microRNAs (miRNAs) that inhibit CSC growth and are down-regulated in CSCs. Aside from the previously identified miR-200 family, these include the miR-15/16 (miR-16, miR-15b) and miR-103/107 (miR-103, miR-107) families as well as miR-145, miR-335, and miR-128b. Interestingly, these miRNAs affect common target genes that encode the Bmi1 and Suz12 components of the polycomb repressor complexes as well as the DNA-binding transcription factors Zeb1, Zeb2, and Klf4. Conversely, expression of the CSC-modulating miRNAs is inhibited by Zeb1 and Zeb2. There is an inverse relationship between the levels of CSC-regulating miRNAs and their respective targets in samples from triple-negative breast cancer patients, providing evidence for the relevance of these interactions in human cancer. In addition, combinatorial overexpression of these miRNAs progressively attenuates the growth of CSCs derived from triple-negative breast cancers. These observations suggest that CSC formation and function are reinforced by an integrated regulatory circuit of miRNAs, transcription factors, and chromatin-modifying activities that can act as a bistable switch to drive cells into either the CSC or the nonstem state within the population of cancer cells. PMID:22908280

  11. Effectiveness of the World Health Organization cancer pain relief guidelines: an integrative review

    Science.gov (United States)

    Carlson, Cathy L

    2016-01-01

    Inadequate cancer pain relief has been documented extensively across historical records. In response, in 1986, the World Health Organization (WHO) developed guidelines for cancer pain treatment. The purpose of this paper is to disseminate the results of a comprehensive, integrative review of studies that evaluate the effectiveness of the WHO guidelines. Studies were included if they: 1) identified patients treated with the guidelines, 2) evaluated self-reported pain, 3) identified instruments used, 4) provided data documenting pain relief, and 5) were written in English. Studies were coded for duration of treatment, definition of pain relief, instruments used, findings related to pain intensity or relief, and whether measures were used other than the WHO analgesic ladder. Twenty-five studies published since 1987 met the inclusion criteria. Evidence indicates 20%–100% of patients with cancer pain can be provided pain relief with the use of the WHO guidelines – while considering their status of treatment or end-of-life care. Due to multiple limitations in included studies, analysis was limited to descriptions. Future research to examine the effectiveness of the WHO guidelines needs to consider recommendations to facilitate study comparisons by standardizing outcome measures. Recent studies have reported that patients with cancer experience pain at moderate or greater levels. The WHO guidelines reflect the knowledge and effectual methods to relieve most cancer pain, but the guidelines are not being adequately employed. Part of the explanation for the lack of adoption of the WHO guidelines is that they may be considered outdated by many because they are not specific to the pharmacological and interventional options used in contemporary pain management practices. The conundrum of updating the WHO guidelines is to encompass the latest pharmacological and interventional innovations while maintaining its original simplicity. PMID:27524918

  12. Physical status of human papillomavirus integration in cervical cancer is associated with treatment outcome of the patients treated with radiotherapy.

    Directory of Open Access Journals (Sweden)

    Hye-Jin Shin

    Full Text Available Integration of human papillomavirus (HPV DNA into the host genome is a critical aetiological event in the progression from normal cervix to intraepithelial neoplasm, and finally to invasive cervical cancer. However, there has been little work on how HPV integration status relates to treatment outcome for cervical carcinomas. In the current study, HPV E2 and E6 gene copy numbers were measured in 111 cervical cancer tissues using real-time QPCR. Integration patterns were divided into four groups: single copy-integrated with episomal components (group 1, single copy-integrated without episomal components (group 2, multicopy tandem repetition-integrated (group 3, and low HPV (group 4 groups. A relapse-predicting model was constructed using multivariable Cox proportional hazards model to classify patients into different risk groups for disease-free survival (DFS. The model was internally validated using bootstrap resampling. Oligonucleotide microarray analysis was performed to evaluate gene expression patterns in relation to the different integration groups. DFS rate was inferior in the order of the patients in group 4, group 2/3, and group 1. Multivariate analysis showed that histologic grade, clinical stage group, and integration pattern were significant prognostic factors for poor DFS. The current prognostic model accurately predicted the risk of relapse, with an area under the receiver operating characteristic curve (AUC of 0.74 (bootstrap corrected, 0.71. In conclusion, these data suggest that HPV integration pattern is a potent prognostic factor for tailored treatment of cervical cancer.

  13. Short-cut calculations for integrated product recovery options in fermentative production of bio-bulk chemicals

    NARCIS (Netherlands)

    Oudshoorn, A.; Berg, C. van den; Roelands, C.P.M.; Straathof, A.J.J.; Wielen, L.A.M. van der

    2010-01-01

    Microorganisms are generally sensitive to high concentrations of products that they excrete. Such product inhibition and toxicity effects can significantly be reduced by the integration of fermentations with separation technologies to remove the products continuously. Cost-calculations are required

  14. High serum YKL-40 levels in patients with primary breast cancer is related to short recurrence free survival

    DEFF Research Database (Denmark)

    Johansen, Julia S; Christensen, Ib Jarle; Riisbro, Rikke;

    2003-01-01

    YKL-40 is a growth factor for connective tissue cells and stimulates migration of endothelial cells. YKL-40 is secreted by cancer cells, and elevated serum YKL-40 in patients with metastatic breast cancer and colorectal cancer is associated with a poorer prognosis as compared to patients...... with normal serum YKL-40. In the present study we evaluated the associations of preoperative serum YKL-40 in 271 patients with primary breast cancer in relation to relapse-free survival and overall survival. The median follow-up time was 5.9 years. There were 77 relapses and 69 patients died. The median serum...... YKL-40 in patients with primary breast cancer at time of operation is only elevated in a small group of patients, but these patients have a shorter recurrence free interval. Further studies are required to determine the biological function of YKL-40 in breast cancer....

  15. Detecting the effect of targeted anti-cancer medicines on single cancer cells using a poly-silicon wire ion sensor integrated with a confined sensitive window.

    Science.gov (United States)

    Wu, You-Lin; Hsu, Po-Yen; Hsu, Chung-Ping; Lin, Jing-Jenn

    2012-10-01

    A mold-cast polydimethylsiloxane (PDMS) confined window was integrated with a poly-silicon wire (PSW) ion sensor. The PSW sensor surface inside the confined window was coated with a 3-aminopropyltriethoxysilane (γ-APTES) sensitive layer which allowed a single living cell to be cultivated. The change in the microenvironment due to the extracellular acidification of the single cell could then be determined by measuring the current flowing through the PSW channel. Based on this, the PSW sensor integrated with a confined sensitive window was used to detect the apoptosis as well as the effect of anti-cancer medicines on the single living non-small-lung-cancer (NSLC) cells including lung adenocarcinoma cancer cells A549 and H1299, and lung squamous-cell carcinoma CH27 cultivated inside the confined window. Single human normal cells including lung fibroblast cells WI38, lung fibroblast cells MRC5, and bronchial epithelium cell Beas-2B were tested for comparison. Two targeted anti-NSCLC cancer medicines, Iressa and Staurosporine, were used in the present study. It was found that the PSW sensor can be used to accurately detect the apoptosis of single cancer cells after the anti-cancer medicines were added. It was also found that Staurosporine is more effective than Iressa in activating the apoptosis of cancer cells.

  16. An integrated microfluidic system for screening of phage-displayed peptides specific to colon cancer cells and colon cancer stem cells.

    Science.gov (United States)

    Che, Yu-Jui; Wu, Huei-Wen; Hung, Lien-Yu; Liu, Ching-Ann; Chang, Hwan-You; Wang, Kuan; Lee, Gwo-Bin

    2015-09-01

    Affinity reagents recognizing biomarkers specifically are essential components of clinical diagnostics and target therapeutics. However, conventional methods for screening of these reagents often have drawbacks such as large reagent consumption, the labor-intensive or time-consuming procedures, and the involvement of bulky or expensive equipment. Alternatively, microfluidic platforms could potentially automate the screening process within a shorter period of time and reduce reagent and sample consumption dramatically. It has been demonstrated recently that a subpopulation of tumor cells known as cancer stem cells possess high drug resistance and proliferation potential and are regarded as the main cause of metastasis. Therefore, a peptide that recognizes cancer stem cells and differentiates them from other cancer cells will be extremely useful in early diagnosis and target therapy. This study utilized M13 phage display technology to identify peptides that bind, respectively, to colon cancer cells and colon cancer stem cells using an integrated microfluidic system. In addition to positive selection, a negative selection process was integrated on the chip to achieve the selection of peptides of high affinity and specificity. We successfully screened three peptides specific to colon cancer cells and colon cancer stem cells, namely, HOLC-1, HOLC-2, and COLC-1, respectively, and their specificity was measured by the capture rate between target, control, and other cell lines. The capture rates are 43.40 ± 7.23%, 45.16 ± 7.12%, and 49.79 ± 5.34% for colon cancer cells and colon cancer stem cells, respectively, showing a higher specificity on target cells than on control and other cell lines. The developed technique may be promising for early diagnosis of cancer cells and target therapeutics.

  17. Human telomeres that carry an integrated copy of human herpesvirus 6 are often short and unstable, facilitating release of the viral genome from the chromosome.

    Science.gov (United States)

    Huang, Yan; Hidalgo-Bravo, Alberto; Zhang, Enjie; Cotton, Victoria E; Mendez-Bermudez, Aaron; Wig, Gunjan; Medina-Calzada, Zahara; Neumann, Rita; Jeffreys, Alec J; Winney, Bruce; Wilson, James F; Clark, Duncan A; Dyer, Martin J; Royle, Nicola J

    2014-01-01

    Linear chromosomes are stabilized by telomeres, but the presence of short dysfunctional telomeres triggers cellular senescence in human somatic tissues, thus contributing to ageing. Approximately 1% of the population inherits a chromosomally integrated copy of human herpesvirus 6 (CI-HHV-6), but the consequences of integration for the virus and for the telomere with the insertion are unknown. Here we show that the telomere on the distal end of the integrated virus is frequently the shortest measured in somatic cells but not the germline. The telomere carrying the CI-HHV-6 is also prone to truncations that result in the formation of a short telomere at a novel location within the viral genome. We detected extra-chromosomal circular HHV-6 molecules, some surprisingly comprising the entire viral genome with a single fully reconstituted direct repeat region (DR) with both terminal cleavage and packaging elements (PAC1 and PAC2). Truncated CI-HHV-6 and extra-chromosomal circular molecules are likely reciprocal products that arise through excision of a telomere-loop (t-loop) formed within the CI-HHV-6 genome. In summary, we show that the CI-HHV-6 genome disrupts stability of the associated telomere and this facilitates the release of viral sequences as circular molecules, some of which have the potential to become fully functioning viruses.

  18. An initial investigation on developing a new method to predict short-term breast cancer risk based on deep learning technology

    Science.gov (United States)

    Qiu, Yuchen; Wang, Yunzhi; Yan, Shiju; Tan, Maxine; Cheng, Samuel; Liu, Hong; Zheng, Bin

    2016-03-01

    In order to establish a new personalized breast cancer screening paradigm, it is critically important to accurately predict the short-term risk of a woman having image-detectable cancer after a negative mammographic screening. In this study, we developed and tested a novel short-term risk assessment model based on deep learning method. During the experiment, a number of 270 "prior" negative screening cases was assembled. In the next sequential ("current") screening mammography, 135 cases were positive and 135 cases remained negative. These cases were randomly divided into a training set with 200 cases and a testing set with 70 cases. A deep learning based computer-aided diagnosis (CAD) scheme was then developed for the risk assessment, which consists of two modules: adaptive feature identification module and risk prediction module. The adaptive feature identification module is composed of three pairs of convolution-max-pooling layers, which contains 20, 10, and 5 feature maps respectively. The risk prediction module is implemented by a multiple layer perception (MLP) classifier, which produces a risk score to predict the likelihood of the woman developing short-term mammography-detectable cancer. The result shows that the new CAD-based risk model yielded a positive predictive value of 69.2% and a negative predictive value of 74.2%, with a total prediction accuracy of 71.4%. This study demonstrated that applying a new deep learning technology may have significant potential to develop a new short-term risk predicting scheme with improved performance in detecting early abnormal symptom from the negative mammograms.

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

    CERN Document Server

    Patel, Manish

    2010-01-01

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

  20. Nutriomes and personalised nutrition for DNA damage prevention, telomere integrity maintenance and cancer growth control.

    Science.gov (United States)

    Fenech, Michael F

    2014-01-01

    DNA damage at the base sequence and chromosome level is a fundamental cause of developmental and degenerative diseases. Multiple micronutrients and their interactions with the inherited and/or acquired genome determine DNA damage and genomic instability rates. The challenge is to identify for each individual the combination of micronutrients and their doses (i.e. the nutriome) that optimises genome stability, including telomere integrity and functionality and DNA repair. Using nutrient array systems with high-content analysis diagnostics of DNA damage, cell death and cell growth, it is possible to define, on an individual basis, the optimal nutriome for DNA damage prevention and cancer growth control. This knowledge can also be used to improve culture systems for cells used in therapeutics such as stem cells to ensure that they are not genetically aberrant when returned to the body. Furthermore, this information could be used to design dietary patterns that deliver the micronutrient combinations and concentrations required for preventing DNA damage by micronutrient deficiency or excess. Using this approach, new knowledge could be obtained to identify the dietary restrictions and/or supplementations required to control specific cancers, which is particularly important given that reliable validated advice is not yet available for those diagnosed with cancer.

  1. Quality of life of Brazilian and Spanish cancer patients undergoing chemotherapy: an integrative literature review

    Directory of Open Access Journals (Sweden)

    Namie Okino Sawada

    2016-01-01

    Full Text Available Objective: characterize the scientific production of Brazil and Spain in regard to methodological aspects and aspects of health-related quality of life experienced by cancer patients receiving chemotherapy in both countries. Method: integrative literature review was conducted using the following databases: CINAHL, MEDLINE, SCOPUS and CUIDEN and the electronic libraries PubMed and SciELO, conducted in September 2013. Results: a total of 28 papers met the inclusion criteria. The synthesis of knowledge was presented in three categories of analysis: assessment of quality of life in different types of cancer; sociodemographic factors that influenced quality of life; and type of cancer and interventions that improve quality of life. Chemotherapy affects health-related quality of life and the most important factors were: age, sex, chemotherapy protocol, type of surgery, stage of the disease, educational level, and emotional intelligence. Complementary therapies such as acupuncture, guided visualization, prayers and exercise were positive and reduced side effects. Conclusion: the results showed a poor level of evidence, since 86% of the studies were cross-sectional descriptive studies; the instrument most frequently used to measure health-related quality of life was EORTC QLQ C-30 and more studies were conducted in Brazil than in Spain.

  2. Gene set based integrated data analysis reveals phenotypic differences in a brain cancer model.

    Directory of Open Access Journals (Sweden)

    Kjell Petersen

    Full Text Available A key challenge in the data analysis of biological high-throughput experiments is to handle the often low number of samples in the experiments compared to the number of biomolecules that are simultaneously measured. Combining experimental data using independent technologies to illuminate the same biological trends, as well as complementing each other in a larger perspective, is one natural way to overcome this challenge. In this work we investigated if integrating proteomics and transcriptomics data from a brain cancer animal model using gene set based analysis methodology, could enhance the biological interpretation of the data relative to more traditional analysis of the two datasets individually. The brain cancer model used is based on serial passaging of transplanted human brain tumor material (glioblastoma--GBM through several generations in rats. These serial transplantations lead over time to genotypic and phenotypic changes in the tumors and represent a medically relevant model with a rare access to samples and where consequent analyses of individual datasets have revealed relatively few significant findings on their own. We found that the integrated analysis both performed better in terms of significance measure of its findings compared to individual analyses, as well as providing independent verification of the individual results. Thus a better context for overall biological interpretation of the data can be achieved.

  3. Solution-based photodetectors for monolithically integrated low-cost short-wave infrared focal plane arrays

    Science.gov (United States)

    Heves, Emre; Kayahan, Huseyin; Gurbuz, Yasar

    2013-05-01

    In this work, PbS Colloidal Quantum Dots (CQD) based photodiodes are realized on both silicon substrates and on the replicas of the ROICs in order to demonstrate fully integrated FPAs. Careful optimization of PbS CQD film formation and ligand exchange process, together with optimization of IC integrable process steps resulted in high performance, monolithically integrable photodiodes. High quantum efficiencies such as 32% is achieved for photodiodes on Si substrates and high responsivities up to 5,73 A/W is achieved for photodiodes on ROIC replicas. Also these detectors achieved very high normalized detectivities such as; 1.36 x 1011 Jones and 1.42 x 1012 Jones under 1V and 2V reverse bias respectively, which is close to conventional InGaAS SWIR detectors.

  4. PET/CT imaging of c-Myc transgenic mice identifies the genotoxic N-nitroso-diethylamine as carcinogen in a short-term cancer bioassay.

    Directory of Open Access Journals (Sweden)

    Katja Hueper

    Full Text Available BACKGROUND: More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay. METHODOLOGY/PRINCIPAL FINDINGS: μCT and ¹⁸F-FDG μPET were used to detect and quantify tumor lesions after treatment with the genotoxic carcinogen NDEA, the tumor promoting agent BHT or the hepatotoxin paracetamol. Tumor growth was investigated between the ages of 4 to 8.5 months and contrast-enhanced μCT imaging detected liver lesions as well as metastatic spread with high sensitivity and accuracy as confirmed by histopathology. Significant differences in the onset of tumor growth, tumor load and glucose metabolism were observed when the NDEA treatment group was compared with any of the other treatment groups. NDEA treatment of c-Myc transgenic mice significantly accelerated tumor growth and caused metastatic spread of HCC in to lung but this treatment also induced primary lung cancer growth. In contrast, BHT and paracetamol did not promote hepatocarcinogenesis. CONCLUSIONS/SIGNIFICANCE: The present study evidences the accuracy of in vivo imaging in defining tumor growth, tumor load, lesion number and metastatic spread. Consequently, the application of in vivo imaging techniques to transgenic animal models may possibly enable short-term cancer bioassays to significantly improve hazard identification and follow-up examinations of different organs by non-invasive methods.

  5. CATTLE (CAncer treatment treasury with linked evidence): An integrated knowledge base for personalized oncology research and practice

    Science.gov (United States)

    Soysal, E; Lee, H‐J; Zhang, Y; Huang, L‐C; Chen, X; Wei, Q; Zheng, W; Chang, JT; Cohen, T; Sun, J

    2017-01-01

    Despite the existence of various databases cataloging cancer drugs, there is an emerging need to support the development and application of personalized therapies, where an integrated understanding of the clinical factors and drug mechanism of action and its gene targets is necessary. We have developed CATTLE (CAncer Treatment Treasury with Linked Evidence), a comprehensive cancer drug knowledge base providing information across the complete spectrum of the drug life cycle. The CATTLE system collects relevant data from 22 heterogeneous databases, integrates them into a unified model centralized on drugs, and presents comprehensive drug information via an interactive web portal with a download function. A total of 2,323 unique cancer drugs are currently linked to rich information from these databases in CATTLE. Through two use cases, we demonstrate that CATTLE can be used in supporting both research and practice in personalized oncology. PMID:28296354

  6. Mortality Among Women With Cervical Cancer During or Shortly After a Pregnancy in Denmark 1968 to 2006

    DEFF Research Database (Denmark)

    Eibye, Simone; Krüger Kjær, Susanne; Nielsen, Thor S S;

    2016-01-01

    to a pregnancy. MATERIALS AND METHODS: From the nationwide Danish Cancer Registry, we identified women diagnosed with a primary cervical cancer at ages 15 to 44 years during 1968 to 2006 born after April 1, 1935. The women were linked to several Danish national registries to obtain information on births...

  7. GRAIL gravity field recovery using the short-arc integral equation technique: development of the latest Graz lunar gravity field model (GrazLGM)

    Science.gov (United States)

    Krauss, S.; Klinger, B.; Baur, O.; Mayr-Guerr, T.

    2015-10-01

    We present an updated version of the lunar gravity field model GrazLGM300a,b [1,2] based on intersatellite Ka-band ranging (KBR) observations collected by the GRAIL mission. We propose to exploit the ranging measurements by an integral equation approach using short orbital arcs [4].Compared to the predecessor model we increase the spectral resolution to degree and order 450 and refined the parameterization. Validation shows that the applied technique is well suited to recover the lunar gravity field.

  8. THE PROCESS OF SHORT-TERM AND LONG-TERM PRICE INTEGRATION IN THE BENIN MAIZE MARKET

    NARCIS (Netherlands)

    LUTZ, C; VANTILBURG, A; VANDERKAMP, BJ

    1995-01-01

    This paper reviews the methodology used to study the price integration process in spatially separated spot markets, and applies if to the Benin maize market. An Autoregressive Distributed Lag Model is derived to take into account the sluggishness of price adjustments. Hypothesis testing concerns sta

  9. Short-term Intensive Neoadjuvant Chemotherapy Improving 10-year Survival for Patients with Stage Ⅱ and Operable Stage Ⅲ Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    BinZhang; YueCai; QiZhang; ZiweiYing; ShulingJiang; HongXu; YongxueZheng; DaqingJiang

    2004-01-01

    OBJECTIVE To evaluate the 10-year curative effects of short-term intensive neoadjuvant chemotherapy for operable breast cancer. METHODS A total of 510 patients with stagell and operable stagelll breast cancer were divided into group A (preoperative neoadjuvant chemotherapy 251 cases) and group B (postoperative adjuvant chemotherapy 259 cases). The patients in group A received short-term and intensive neoadjuvant chemotherapy for 4 weeks followed by modified radical mastectomy two weeks after the chemotherapy. The postoperative adjuvant chemotherapy began within two weeks after surgery. The same chemotherapeutic regimen was used for both groups. RESULTS For stage Ⅲ in group A the 5-year overall survival rate (OS) and disease-free survival rate (DFS) were 59.2% and 54.9% respectively which were higher than those in group B (28.3% and 20.8% respectively, P<0.05). The 10-year OS and DFS were 78.1% and 73.5% respectively for stage Ⅱ in group A which were higher than those in group B (68.4% and 60.7%, P<0.05). The 10-year OS and DFS were 42.3% and 40.4% respectively forstage Ⅲ in group A which were higher than those in group B (20.4% and 18.4% respectively, P<0.05). CONCLUSION The results showed that intensive neoadjuvant chemotherapy can improve the 10-year survival for patients with stage Ⅱ and operablestage Ⅲ breast cancer.

  10. Laparoscopic-assisted gastrectomy versus open gastrectomy for T4a gastric cancer in short-term and long-term outcomes.

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Objective:To study thesafety of oncologic short-term and long-term outcomes of laparoscopic-assisted gastrectomy (LAG) performed for T4a stage gastric cancer. Methods: Between January 2009 and December 2014, 86 patients with American Joint Committee on Cancer (AJCC) stage T4a gastric cancer underwent LAG or conventional open gastrectomy (OG). Of these patients, 43 patients underwent LAG and they were compared with patients who underwent OG regarding short-term and long-term outcome. Results:The N stage (P=0.685) did not differ between the LAG and OG groups. Postoperative morbidity occurred in 6 (14.0%) OG and 8 (9.3%) LAG cases and postoperative mortality occurred 2 (4.0%) and 0 (0.0%) cases of OG and LAG, respectively. Recurrence occurred in 6 (14.0%) cases and 4 (9.3%) case in the OG and LAG group, respectively (P=0.077). hTe mean survival time in the OG group was 53.86 m)and in the LAG was 53.97 m with no signiifcant difference (P=0.295).Conclusion:The LAG is a feasible and safe procedure, and has several advantages over conventional OG.

  11. Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers.

    Directory of Open Access Journals (Sweden)

    Yuichi Shiraishi

    Full Text Available Recent studies applying high-throughput sequencing technologies have identified several recurrently mutated genes and pathways in multiple cancer genomes. However, transcriptional consequences from these genomic alterations in cancer genome remain unclear. In this study, we performed integrated and comparative analyses of whole genomes and transcriptomes of 22 hepatitis B virus (HBV-related hepatocellular carcinomas (HCCs and their matched controls. Comparison of whole genome sequence (WGS and RNA-Seq revealed much evidence that various types of genomic mutations triggered diverse transcriptional changes. Not only splice-site mutations, but also silent mutations in coding regions, deep intronic mutations and structural changes caused splicing aberrations. HBV integrations generated diverse patterns of virus-human fusion transcripts depending on affected gene, such as TERT, CDK15, FN1 and MLL4. Structural variations could drive over-expression of genes such as WNT ligands, with/without creating gene fusions. Furthermore, by taking account of genomic mutations causing transcriptional aberrations, we could improve the sensitivity of deleterious mutation detection in known cancer driver genes (TP53, AXIN1, ARID2, RPS6KA3, and identified recurrent disruptions in putative cancer driver genes such as HNF4A, CPS1, TSC1 and THRAP3 in HCCs. These findings indicate genomic alterations in cancer genome have diverse transcriptomic effects, and integrated analysis of WGS and RNA-Seq can facilitate the interpretation of a large number of genomic alterations detected in cancer genome.

  12. The Effect of Endoscopic Resection on Short-Term Surgical Outcomes in Patients with Additional Laparoscopic Gastrectomy after Non-Curative Resection for Gastric Cancer

    Science.gov (United States)

    Lee, Eun-Gyeong; Eom, Bang-Wool; Yoon, Hong-Man; Kim, Yong-Il; Cho, Soo-Jeong; Lee, Jong-Yeul; Kim, Young-Woo

    2017-01-01

    Purpose Endoscopic submucosal dissection (ESD) in early gastric cancer causes an artificial gastric ulcer and local inflammation that has a negative intraprocedural impact on additional laparoscopic gastrectomy in patients with noncurative ESD. In this study, we analyzed the effect of ESD on short-term surgical outcomes and evaluated the risk factors. Materials and Methods From January 2003 to January 2013, 1,704 patients of the National Cancer Center underwent laparoscopic gastrectomy with lymph node dissection because of preoperative stage Ia or Ib gastric cancer. They were divided into 2 groups: (1) with preoperative ESD or (2) without preoperative ESD. Clinicopathologic factors and short-term surgical outcomes were retrospectively evaluated along with risk factors such as preoperative ESD. Results Several characteristics differed between patients who underwent ESD-surgery (n=199) or surgery alone (n=1,505). The mean interval from the ESD procedure to the operation was 43.03 days. Estimated blood loss, open conversion rate, mean operation time, and length of hospital stay were not different between the 2 groups. Postoperative complications occurred in 23 patients (11.56%) in the ESD-surgery group and in 189 patients (12.56%) in the surgery-only group, and 3 deaths occurred among patients with complications (1 patient [ESD-surgery group] vs. 2 patients [surgery-only group]; P=0.688). A history of ESD was not significantly associated with postoperative complications (P=0.688). Multivariate analysis showed that male sex (P=0.008) and laparoscopic total or proximal gastrectomy (P=0.000) were independently associated with postoperative complications. Conclusions ESD did not affect short-term surgical outcomes during and after an additional laparoscopic gastrectomy.

  13. Leadership emergence over time in short-lived groups: Integrating expectations states theory with temporal person-perception and self-serving bias.

    Science.gov (United States)

    Kalish, Yuval; Luria, Gil

    2016-10-01

    Research into leadership emergence typically focuses on the attributes of the emergent leader. By considering also the attributes of perceivers and the passage of time, we develop a more complete theory of leadership emergence in short-lived groups. Using expectation states theory as an overarching theoretical framework, and integrating it with the surface- and deep-level diversity literature and with theories of self-serving biases, we examine the predictors of leadership emergence in short timeframes. We conduct a field study in a military assessment boot camp (a pilot study, n = 60; and a main study, n = 89). We use cross-sectional and longitudinal exponential random graph models to analyze data on participants' abilities and on their perceptions of who, in their respective groups, were "leaders." We find that the criteria by which people perceive leadership in others change over time, from easily noticeable attributes to covert leadership-relevant attributes, and that people also rely on leadership-relevant attributes that they possess at high levels to inform their perceptions of leadership in others. The integration of expectation states theory, attribute salience over time and theories of self-serving bias is needed for a full understanding of leadership emergence in groups, because perceivers' own abilities are instrumental in shaping their perceptions of emergent leadership over time. Theoretical and practical implications are discussed. (PsycINFO Database Record

  14. An autoregressive integrated moving average model for short-term prediction of hepatitis C virus seropositivity among male volunteer blood donors in Karachi, Pakistan

    Institute of Scientific and Technical Information of China (English)

    Saeed Akhtar; Shafquat Rozi

    2009-01-01

    AIM: To identify the stochastic autoregressive integrated moving average (ARIMA) model for short term forecasting of hepatitis C virus (HCV) seropositivity among volunteer blood donors in Karachi, Pakistan. METHODS: Ninety-six months (1998-2005) data on volunteer blood donors tested at four major blood banks in Karachi, Pakistan were subjected to ARIMA modeling. Subsequently, a fitted ARIMA model was used to forecast HCV seropositive donors for 91-96 mo to contrast with observed series of the same months. To assess the forecast accuracy, the mean absolute error rate (%) between the observed and predicted HCV seroprevalence was calculated. Finally, a fitted ARIMA model was used for short-term forecasts beyond the observed series. RESULTS: The goodness-of-fit test of the optimum ARIMA (2,1,7) model showed non- s igni f icant autocorrelations in the residuals of the model. The forecasts by ARIMA for 91-96 mo closely followed the pattern of observed series for the same months, with mean monthly absolute forecast errors (%) over 6 mo of 6.5%. The short-term forecasts beyond the observed series adequately captured the pattern in the data and showed increasing tendency of HCV seropositivity with CONCLUSION: To curtail HCV spread, public health authorities need to educate communities and health care providers about HCV transmission routes based on known HCV epidemiology in Pakistan and its neighboring countries. Future research may focus on factors associated with hyperendemic levels of HCV infection.

  15. False-positive findings in mammography screening induces short-term distress - breast cancer-specific concern prevails longer

    DEFF Research Database (Denmark)

    Aro, A R; Pilvikki Absetz, S; van Elderen, T M

    2000-01-01

    -ups at 2 and 12 months postscreening. At 2 months, there was a moderate multivariate effect of group on distress; and intrusive thinking and worry about breast cancer, in particular, were most frequent amongst the false positives. Intrusive thinking still prevailed at 12 months, in addition to a higher...... perceived breast cancer risk and susceptibility. Distress related to screening and false-positive findings seems to be moderate, but prevailing cancer-specific concerns call for improvements in screening programmes....... findings (n=1407), false-positive findings (n=492) and referents from outside the screening programme (n=1718, age 48-49 years). Distress was measured as illness worry, anxiety, depression, cancer beliefs and early detection behaviour. Measurements were one month before screening invitation with follow...

  16. Cancer gene prioritization by integrative analysis of mRNA expression and DNA copy number data: a comparative review

    CERN Document Server

    Lahti, Leo; Klein, Hans-Ulrich; Bicciato, Silvio; Dugas, Martin

    2011-01-01

    A variety of genome-wide profiling techniques are available to probe complementary aspects of genome structure and function. Integrative analysis of heterogeneous data sources can reveal higher-level interactions that cannot be detected based on individual observations. A standard integration task in cancer studies is to identify altered genomic regions that induce changes in the expression of the associated genes based on joint analysis of genome-wide gene expression and copy number profiling measurements. In this review, we provide a comparison among various modeling procedures for integrating genome-wide profiling data of gene copy number and transcriptional alterations and highlight common approaches to genomic data integration. A transparent benchmarking procedure is introduced to quantitatively compare the cancer gene prioritization performance of the alternative methods. The benchmarking algorithms and data sets are available at http://intcomp.r-forge.r-project.org

  17. Barriers to Integration of Traditional and Complementary Medicine in Supportive Cancer Care of Arab Patients in Northern Israel

    Directory of Open Access Journals (Sweden)

    Eran Ben-Arye

    2012-01-01

    Full Text Available In 2008, an Integrative Oncology Program (IOP, aiming to improve patients’ quality of life during chemotherapy and advanced cancer, was launched within the Clalit Health Organization's oncology service at the Lin Medical Center, Haifa, Israel. The IOP clinical activity is documented using a research-based registry protocol. In this study, we present an analysis of the registry protocol of 15 Arab patients with cancer who were referred to the IOP. Analysis of patients’ reported outcomes using the Edmonton Symptom Assessment Scale suggests that integrative medicine care improves fatigue (=0.024, nausea (=0.043, depression (=0.012, anxiety (=0.044, appetite (=0.012, and general well-being (=0.031. Barriers to integration of traditional and complementary medicine in supportive care of Arab patients are discussed followed by six practical recommendations aimed at improving accessibility of patients to integrative supportive care, as well as compliance with treatments.

  18. Short-term treatment with glucosamine hydrochloride specifically downregulates hypoxia-inducible factor-1α at the protein level in YD-8 human tongue cancer cells.

    Science.gov (United States)

    Jo, Jeong-Rang; Park, Yu-Kyoung; Jang, Byeong-Churl

    2014-05-01

    Hypoxia-inducible factor-1 (HIF-1) is a tumor angiogenic transcription factor composed of an α and β subunit. We investigated the effect of glucosamine hydrochloride (GS-HCl) on the expression of HIF-1α and HIF-1β in serum‑treated YD-8 human tongue cancer cells. While long-term (24 h) treatment with GS-HCl strongly repressed the expression of HIF-1α and HIF-1β at both the protein and mRNA levels, short-term (4 h) GS-HCl treatment inhibited HIF-1α at the protein level. Short-term GS-HCl treatment also decreased phosphorylation of p70S6K and S6, translation-related proteins. However, the results of subsequent pharmacological inhibition and protein stability analyses indicated that HIF-1α protein downregulation induced by short-term GS-HCl treatment was not through modulation of the mTOR/p70S6K/S6 signaling pathways, the 26S proteasomal and lysosomal activities and HIF-1α protein stability. Importantly, our further analyses identified that HIF-1α protein downregulation induced by short-term GS-HCl treatment was blunted by exogenous administration of the citric acid cycle metabolites citrate and 2-oxoglutarate, but not the glycolytic end byproducts pyruvate and lactate. These findings demonstrate firstly that short-term GS treatment selectively downregulates HIF-1α at the protein level in YD-8 cells via interference of production of the citric acid cycle metabolites. It is proposed that short-term GS-HCl exposure may be applied for the treatment of oral tumors with high expression of HIF-1α.

  19. Second Cancer Risk after simultaneous integrated boost radiation therapy of right sided breast cancer with and without flattening filter

    Energy Technology Data Exchange (ETDEWEB)

    Dobler, Barbara; Maier, Johannes; Knott, Bernadette; Maerz, Manuel; Koelbl, Oliver [Regensburg University Medical Center, Department of Radiotherapy, Regensburg (Germany); Loeschel, Rainer [Ostbayerische Technische Hochschule Regensburg, Faculty of Computer Science and Mathematics, Regensburg (Germany)

    2016-10-15

    The aim of this study was to investigate if the flattening filter free mode (FFF) of a linear accelerator reduces the excess absolute risk (EAR) for second cancer as compared to the flat beam mode (FF) in simultaneous integrated boost (SIB) radiation therapy of right-sided breast cancer. Six plans were generated treating the whole breast to 50.4 Gy and a SIB volume to 63 Gy on CT data of 10 patients: intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and a tangential arc VMAT (tVMAT), each with flattening filter and without. The EAR was calculated for the contralateral breast and the lungs from dose-volume histograms (DVH) based on the linear-exponential, the plateau, and the full mechanistic dose-response model. Peripheral low-dose measurements were performed to compare the EAR in more distant regions as the thyroids and the uterus. FFF reduces the EAR significantly in the contralateral and peripheral organs for tVMAT and in the peripheral organs for VMAT. No reduction was found for IMRT. The lowest EAR for the contralateral breast and lung was achieved with tVMAT FFF, reducing the EAR by 25 % and 29 % as compared to tVMAT FF, and by 44 % to 58 % as compared to VMAT and IMRT in both irradiation modes. tVMAT FFF showed also the lowest peripheral dose corresponding to the lowest EAR in the thyroids and the uterus. The use of FFF mode allows reducing the EAR significantly when tVMAT is used as the treatment technique. When second cancer risk is a major concern, tVMAT FFF is considered the preferred treatment option in SIB irradiation of right-sided breast cancer. (orig.) [German] Ziel der Studie war es zu untersuchen, ob der ausgleichskoerperfreie Modus (FFF) bei der simultan integrierten Boost-(SIB-)Bestrahlung des rechtsseitigen Mammakarzinoms eine Reduktion des strahleninduzierten Sekundaermalignomrisikos (''excess absolute risk'', EAR) im Vergleich zur Bestrahlung mit Ausgleichskoerper (FF) erlaubt. Auf CT

  20. Global Integration of the Hot-State Brain Network of Appetite Predicts Short Term Weight Loss in Older Adult

    Directory of Open Access Journals (Sweden)

    Brielle M Paolini

    2015-05-01

    Full Text Available Obesity is a public health crisis in North America. While lifestyle interventions for weight loss (WL remain popular, the rate of success is highly variable. Clearly, self-regulation of eating behavior is a challenge and patterns of activity across the brain may be an important determinant of success. The current study prospectively examined whether integration across the Hot-State Brain Network of Appetite (HBN-A predicts WL after 6-months of treatment in older adults. Our metric for network integration was global efficiency (GE. The present work is a sub-study (n = 56 of an ongoing randomized clinical trial involving WL. Imaging involved a baseline food-cue visualization functional MRI (fMRI scan following an overnight fast. Using graph theory to build functional brain networks, we demonstrated that regions of the HBN-A (insula, anterior cingulate cortex (ACC, superior temporal pole, amygdala and the parahippocampal gyrus were highly integrated as evidenced by the results of a principal component analysis. After accounting for known correlates of WL (baseline weight, age, sex, and self-regulatory efficacy and treatment condition, which together contributed 36.9% of the variance in WL, greater GE in the HBN-A was associated with an additional 19% of the variance. The ACC of the HBN-A was the primary driver of this effect, accounting for 14.5% of the variance in WL when entered in a stepwise regression following the covariates, p = 0.0001. The HBN-A is comprised of limbic regions important in the processing of emotions and visceral sensations and the ACC is key for translating such processing into behavioral consequences. The improved integration of these regions may enhance awareness of body and emotional states leading to more successful self-regulation and to greater WL. This is the first study among older adults to prospectively demonstrate that, following an overnight fast, GE of the HBN-A during a food visualization task is predictive of

  1. [Playful strategies for data collection with child cancer patients: an integrative review].

    Science.gov (United States)

    Sposito, Amanda Mota Pacciulio; de Sparapani, Valéria Cássia; Pfeifer, Luzia Iara; de Lima, Regina Aparecida Garcia; Nascimento, Lucila Castanheira

    2013-09-01

    Children are the best sources of information on their experiences and opinions, and qualitative studies have favored the development and application of techniques that facilitate their self-expression and approaching the researcher. Through an integrative literature review, the objective of this research was to identify playful resources used in qualitative research data collection with child cancer patients, and their forms of application. Systemized searches of electronic databases and a virtual library were undertaken, which, combined with a non-systemized sample, totaled 15 studies spanning the period from 2000 and 2010. Drawing, toys, puppets, photography and creativity and sensitivity dynamics were identified which, in association with interviews or not, were shown to directly or indirectly facilitate data collection, thereby broadening the interaction with the children, and permitting further expression of their feelings. The advantages and limitations of using these resources are presented thus contributing to planning research with children.

  2. An Integrated Genome-Wide Systems Genetics Screen for Breast Cancer Metastasis Susceptibility Genes.

    Directory of Open Access Journals (Sweden)

    Ling Bai

    2016-04-01

    Full Text Available Metastasis remains the primary cause of patient morbidity and mortality in solid tumors and is due to the action of a large number of tumor-autonomous and non-autonomous factors. Here we report the results of a genome-wide integrated strategy to identify novel metastasis susceptibility candidate genes and molecular pathways in breast cancer metastasis. This analysis implicates a number of transcriptional regulators and suggests cell-mediated immunity is an important determinant. Moreover, the analysis identified novel or FDA-approved drugs as potentially useful for anti-metastatic therapy. Further explorations implementing this strategy may therefore provide a variety of information for clinical applications in the control and treatment of advanced neoplastic disease.

  3. Friend leukemia virus integration 1 activates the Rho GTPase pathway and is associated with metastasis in breast cancer.

    Science.gov (United States)

    Song, Wei; Li, Wei; Li, Lingyu; Zhang, Shilin; Yan, Xu; Wen, Xue; Zhang, Xiaoying; Tian, Huimin; Li, Ailing; Hu, Ji-Fan; Cui, Jiuwei

    2015-09-15

    Breast cancer is the most prevalent malignant disease in women worldwide. In patients with breast cancer, metastasis to distant sites directly determines the survival outcome. However, the molecular mechanism underlying metastasis in breast cancer remains to be defined. In this report, we found that Friend leukemia virus integration 1 (FLI1) proto-oncogene was differentially expressed between the aggressive MDA-MB231 and the non-aggressive MCF-7 breast cancer cells. Congruently, immunohistochemical staining of clinical samples revealed that FLI1 was overexpressed in breast cancers as compared with the adjacent tissues. The abundance of FLI1 protein was strongly correlated with the advanced stage, poor differentiation, and lymph node metastasis in breast cancer patients. Knockdown of FLI1 with small interfering RNAs significantly attenuated the potential of migration and invasion in highly metastatic human breast cancer cells. FLI1 oncoprotein activated the Rho GTPase pathway that is known to play a role in tumor metastasis. This study for the first time identifies FLI1 as a clinically and functionally important target gene of metastasis, providing a rationale for developing FLI1 inhibitors in the treatment of breast cancer.

  4. Integrated ecological hazard assessment of waste site soil extracts using FETAX and short-term fathead minnow teratogenesis assay

    Energy Technology Data Exchange (ETDEWEB)

    Fort, D.J.; Stover, E.L. [Stover Group, Stillwater, OK (United States); Bantle, J.A. [Oklahoma State Univ., Stillwater, OK (United States)

    1996-12-31

    Frog Embryo Teratogenesis Assay-Xenopus (FETAX) is a 96-h whole embryo-larval assay designed to detect environmental developmental toxicants for use in ecological hazard assessment. FETAX offers several advantages in integrated biological hazard assessment including, time- and cost-effectiveness, technical ease, and versatility. FETAX has undergone extensive intra- and more recently interlaboratory validation with known mammalian teratogens and non-teratogens. Ecological hazard evaluations of contaminated sediments, waste site soils, and complex surface and groundwaters have also been performed. An integrated hazard assessment study using FETAX, the conventional, Pimephales promelas 7-d teratogenecity test, and an abbreviated P. promelas teratogenecity test utilizing the general FETAX protocol was conducted with specific reference toxicants and aqueous extracts of contaminated hazardous waste site soils. Results from the studies indicated that FETAX can be used as a component of a battery of bioassays designed to assess potential ecological hazard. Furthermore, the generalized FETAX protocol may be useful with other species in evaluating developmental toxicity hazard.

  5. Integrating the interpersonal psychological theory of suicide into the depression/suicidal ideation relationship: a short-term prospective study.

    Science.gov (United States)

    Kleiman, Evan M; Liu, Richard T; Riskind, John H

    2014-03-01

    We examined the hypothesis that depressive symptoms are associated with increased beliefs about perceived burdensomeness and thwarted belongingness identified in the interpersonal psychological theory of suicide and that these beliefs are associated with changes in suicidal ideation. Participants with clinical levels of depressive symptoms (n=299) were selected from a larger group (n=508) and completed measures of depressive symptoms, perceived burdensomeness and thwarted belongingness, and suicidal ideation twice over a period of 2 months. Results of a structural equation model found that depressive symptoms were associated with increases in burdensomeness and lack of belonging, which were associated with suicidal ideation. Moreover, this hypothesized integrated model demonstrated a significantly better fit than an alternative model that assumed burdensomeness and lack of belonging were associated with changes in depressive symptoms, which were associated with suicidal ideation. Our findings suggest that the well-established relationship between depressive symptoms and suicidal ideation is associated with changes in beliefs that one is a burden on others and lacks belonging. More generally, these results suggest that it may be fruitful to integrate theories of suicide risk to form a comprehensive model that can inform future research and clinical interventions.

  6. Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Brisset

    Full Text Available Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (p<0.05. These studies suggest that PRM imaging biomarkers are useful for detection of the impact of prostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease.

  7. Phase II Study of Preoperative Helical Tomotherapy With a Simultaneous Integrated Boost for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Engels, Benedikt; Tournel, Koen [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium); Everaert, Hendrik [Department of Nuclear Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium); Hoorens, Anne [Department of Pathology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium); Sermeus, Alexandra [Department of Gastroenterology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium); Christian, Nicolas; Storme, Guy; Verellen, Dirk [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium); De Ridder, Mark, E-mail: mark.deridder@uzbrussel.be [Department of Radiotherapy, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels (Belgium)

    2012-05-01

    Purpose: The addition of concomitant chemotherapy to preoperative radiotherapy is considered the standard of care for patients with cT3-4 rectal cancer. The combined treatment modality increases the complete response rate and local control (LC), but has no impact on survival or the incidence of distant metastases. In addition, it is associated with considerable toxicity. As an alternative strategy, we explored prospectively, preoperative helical tomotherapy with a simultaneous integrated boost (SIB). Methods and Materials: A total of 108 patients were treated with intensity-modulated and image-guided radiotherapy using the Tomotherapy Hi-Art II system. A dose of 46 Gy, in daily fractions of 2 Gy, was delivered to the mesorectum and draining lymph nodes, without concomitant chemotherapy. Patients with an anticipated circumferential resection margin (CRM) of less than 2 mm, based on magnetic resonance imaging, received a SIB to the tumor up to a total dose of 55.2 Gy. Acute and late side effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: A total of 102 patients presented with cT3-4 tumors; 57 patients entered the boost group and 51 the no-boost group. One patient in the no-boost group developed a radio-hypersensitivity reaction, resulting in a complete tumor remission, a Grade 3 acute and Grade 5 late enteritis. No other Grade {>=}3 acute toxicities occurred. With a median follow-up of 32 months, Grade {>=}3 late gastrointestinal and urinary toxicity were observed in 6% and 4% of the patients, respectively. The actuarial 2-year LC, progression-free survival and overall survival were 98%, 79%, and 93%. Conclusions: Preoperative helical tomotherapy displays a favorable acute toxicity profile in patients with cT3-4 rectal cancer. A SIB can be safely administered in patients with a narrow CRM and resulted in a promising LC.

  8. Dosimetric evaluation of simultaneous integrated boost during stereotactic body radiation therapy for pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Wensha, E-mail: wensha.yang@cshs.org [Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States); Reznik, Robert; Fraass, Benedick A. [Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States); Nissen, Nicholas [Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA (United States); Hendifar, Andrew [Department of Gastrointestinal Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States); Wachsman, Ashley [Department of Cross-Sectional Imaging Interventional Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States); Sandler, Howard; Tuli, Richard [Department of Radiation Oncology, Cedars Sinai Medical Center, Los Angeles, CA (United States)

    2015-04-01

    Stereotactic body radiation therapy (SBRT) provides a promising way to treat locally advanced pancreatic cancer and borderline resectable pancreatic cancer. A simultaneous integrated boost (SIB) to the region of vessel abutment or encasement during SBRT has the potential to downstage otherwise likely positive surgical margins. Despite the potential benefit of using SIB-SBRT, the ability to boost is limited by the local geometry of the organs at risk (OARs), such as stomach, duodenum, and bowel (SDB), relative to tumor. In this study, we have retrospectively replanned 20 patients with 25 Gy prescribed to the planning target volume (PTV) and 33~80 Gy to the boost target volume (BTV) using an SIB technique for all patients. The number of plans and patients able to satisfy a set of clinically established constraints is analyzed. The ability to boost vessels (within the gross target volume [GTV]) is shown to correlate with the overlap volume (OLV), defined to be the overlap between the GTV + a 1(OLV1)- or 2(OLV2)-cm margin with the union of SDB. Integral dose, boost dose contrast (BDC), biologically effective BDC, tumor control probability for BTV, and normal tissue complication probabilities are used to analyze the dosimetric results. More than 65% of the cases can deliver a boost to 40 Gy while satisfying all OAR constraints. An OLV2 of 100 cm{sup 3} is identified as the cutoff volume: for cases with OLV2 larger than 100 cm{sup 3}, it is very unlikely the case could achieve 25 Gy to the PTV while successfully meeting all the OAR constraints.

  9. Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis.

    Science.gov (United States)

    Ramakrishna, Manasa; Williams, Louise H; Boyle, Samantha E; Bearfoot, Jennifer L; Sridhar, Anita; Speed, Terence P; Gorringe, Kylie L; Campbell, Ian G

    2010-04-08

    Ovarian cancer is a disease characterised by complex genomic rearrangements but the majority of the genes that are the target of these alterations remain unidentified. Cataloguing these target genes will provide useful insights into the disease etiology and may provide an opportunity to develop novel diagnostic and therapeutic interventions. High resolution genome wide copy number and matching expression data from 68 primary epithelial ovarian carcinomas of various histotypes was integrated to identify genes in regions of most frequent amplification with the strongest correlation with expression and copy number. Regions on chromosomes 3, 7, 8, and 20 were most frequently increased in copy number (> 40% of samples). Within these regions, 703/1370 (51%) unique gene expression probesets were differentially expressed when samples with gain were compared to samples without gain. 30% of these differentially expressed probesets also showed a strong positive correlation (r > or =0.6) between expression and copy number. We also identified 21 regions of high amplitude copy number gain, in which 32 known protein coding genes showed a strong positive correlation between expression and copy number. Overall, our data validates previously known ovarian cancer genes, such as ERBB2, and also identified novel potential drivers such as MYNN, PUF60 and TPX2.

  10. Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis.

    Directory of Open Access Journals (Sweden)

    Manasa Ramakrishna

    Full Text Available Ovarian cancer is a disease characterised by complex genomic rearrangements but the majority of the genes that are the target of these alterations remain unidentified. Cataloguing these target genes will provide useful insights into the disease etiology and may provide an opportunity to develop novel diagnostic and therapeutic interventions. High resolution genome wide copy number and matching expression data from 68 primary epithelial ovarian carcinomas of various histotypes was integrated to identify genes in regions of most frequent amplification with the strongest correlation with expression and copy number. Regions on chromosomes 3, 7, 8, and 20 were most frequently increased in copy number (> 40% of samples. Within these regions, 703/1370 (51% unique gene expression probesets were differentially expressed when samples with gain were compared to samples without gain. 30% of these differentially expressed probesets also showed a strong positive correlation (r > or =0.6 between expression and copy number. We also identified 21 regions of high amplitude copy number gain, in which 32 known protein coding genes showed a strong positive correlation between expression and copy number. Overall, our data validates previously known ovarian cancer genes, such as ERBB2, and also identified novel potential drivers such as MYNN, PUF60 and TPX2.

  11. Interest in Integrative Medicine Among Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

    Science.gov (United States)

    Hack, Carolin C; Fasching, Peter A; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesslet, Thomas; Fischer, Gunnar; Henschen, Stefan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y; Wallwiener, Diethelm; Kümmel, Sherko; Beckmann, Matthias W; Paepke, Daniela

    2016-09-14

    Background Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine. Methods The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive primary breast cancer. Between 2008 and 2009, 5045 postmenopausal patients were enrolled at 339 certified breast centers in Germany. As part of the data collection process, patients were asked at the baseline about their interest in and information needs relating to integrative medicine. Results Of the 5045 patients recruited, 3411 responded to the questionnaire on integrative medicine and took part in the analysis, 1583 patients expressed an interest in integrative medicine, and 1828 patients declared no interest. Relevant predictors of interest in integrative medicine were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in integrative medicine declined highly significantly (P 65 years, 38.0%). Patients in favor of integrative medicine were significantly less satisfied with the information received about individual treatments and antihormonal therapy. Patients with interest in integrative medicine were more often interested in rehabilitation and fitness, nutritional counseling, and additional support from self-help organizations. These women were mostly interested in receiving information about their disease and integrative medicine from a physician, rather than from other sources. Conclusions This study shows that a considerable proportion of postmenopausal breast cancer patients are interested in

  12. Addressing the unique psychosocial barriers to breast cancer treatment experienced by African-American women through integrative navigation.

    Science.gov (United States)

    Chatman, Michelle C; Green, Rodney D

    2011-12-01

    African-American women face a disproportionally high breast cancer mortality rate and a significantly low five-year survival rate after breast cancer treatment. This study investigated, through a series of focus groups, how 32 African-American women (N = 32) breast cancer patients and survivors managed their cancer-related health needs. Participants also reported important barriers to care including problematic interactions with medical professionals, challenges in intimate relations, difficulties in handling the stigma and myths about breast cancer, and the psychological challenges that they faced. A patient navigation model was implemented at an eastern urban hospital that emphasized integrative therapies such as meditation, nutritional instruction, and yoga. Follow-up telephone interviews with 37 additional African-American participants (N = 37) indicated the rating of effectiveness to be at 3.8 to 3.9 out of 4 for the integrative patient navigation program. Over half of the survivors reported using some complementary techniques after treatment was completed, thus suggesting a long-term improvement in their quality of life as a result of the integrative techniques.

  13. The Integration of Technology and Management in the Competitiveness of the United States Short Staple Yarn Manufacturing Industry

    Directory of Open Access Journals (Sweden)

    Suvalee T. Tangboonritruthai

    2014-01-01

    Full Text Available The purpose of this research was to investigate whether a balance of technology and management could be used in order to sustain a viable United States (US short staple yarn production industry. The methodology used in this study consisted of primary research comprising two phases. The first phase consisted of interviews with industry executives in order to find out what US yarn manufacturers think are the important factors in maintaining a competitive yarn industry. The second phase was an online survey with industry customers in order to find out why weavers and knitters buy from US manufacturers. Results reveal that US manufacturers have competitive advantages over other countries because of skill level of workforce, variety of products offered, customer relationships, innovation and technology, and product quality. In order to keep these competitive advantages, “technology” and “management” strategies should be implemented. Results also reveal the areas in which the US yarn manufacturers should focus their resources in order to stay competitive or indeed survive.

  14. Integration of MODIS data and short baseline subset (SBAS) technique for land subsidence monitoring in Datong, China

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, C.Y.; Zhang, Q.; Yang, C.S.; Zou, W.B. [Changan University, Xian (China)

    2011-07-15

    Datong is located in the north of Shanxi Province, which is famous for its old-fashioned coal-mining preservation in China. Some serious issues such as land subsidence, ground fissures, mining collapse, and earthquake hazards have occurred over this area for a long time resulting in significant damages to buildings and roads. In order to monitor and mitigate these natural man-made hazards, Short Baseline Subsets (SBAS) InSAR technique with ten Envisat ASAR data is applied to detect the surface deformation over an area of thousands of square kilometers. Then, five MODIS data are used to check the atmospheric effects on InSAR interferograms. Finally, nine nonlinear land subsidence cumulative results during September 2004 and February 2008 are obtained. Based on the deformation data, three kinds of land subsidence are clearly detected, caused by mine extraction, underground water withdrawal and construction of new economic zones, respectively. The annual mean velocity of subsidence can reach 1 to 4 cm/year in different subsidence areas. A newly designed high-speed railway (HSR) with speeds of 350 km/h will cross through the Datong hi-tech zone. Special measures should be taken for the long run of this project. In addition, another two subsidence regions need further investigation to mitigate such hazards.

  15. Short-Chain 3-Hydroxyacyl-Coenzyme A Dehydrogenase Associates with a Protein Super-Complex Integrating Multiple Metabolic Pathways

    Science.gov (United States)

    Narayan, Srinivas B.; Master, Stephen R.; Sireci, Anthony N.; Bierl, Charlene; Stanley, Paige E.; Li, Changhong; Stanley, Charles A.; Bennett, Michael J.

    2012-01-01

    Proteins involved in mitochondrial metabolic pathways engage in functionally relevant multi-enzyme complexes. We previously described an interaction between short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD) and glutamate dehydrogenase (GDH) explaining the clinical phenotype of hyperinsulinism in SCHAD-deficient patients and adding SCHAD to the list of mitochondrial proteins capable of forming functional, multi-pathway complexes. In this work, we provide evidence of SCHAD's involvement in additional interactions forming tissue-specific metabolic super complexes involving both membrane-associated and matrix-dwelling enzymes and spanning multiple metabolic pathways. As an example, in murine liver, we find SCHAD interaction with aspartate transaminase (AST) and GDH from amino acid metabolic pathways, carbamoyl phosphate synthase I (CPS-1) from ureagenesis, other fatty acid oxidation and ketogenesis enzymes and fructose-bisphosphate aldolase, an extra-mitochondrial enzyme of the glycolytic pathway. Most of the interactions appear to be independent of SCHAD's role in the penultimate step of fatty acid oxidation suggesting an organizational, structural or non-enzymatic role for the SCHAD protein. PMID:22496890

  16. Predictive Modeling of Chemical Hazard by Integrating Numerical Descriptors of Chemical Structures and Short-term Toxicity Assay Data

    Science.gov (United States)

    Rusyn, Ivan; Sedykh, Alexander; Guyton, Kathryn Z.; Tropsha, Alexander

    2012-01-01

    Quantitative structure-activity relationship (QSAR) models are widely used for in silico prediction of in vivo toxicity of drug candidates or environmental chemicals, adding value to candidate selection in drug development or in a search for less hazardous and more sustainable alternatives for chemicals in commerce. The development of traditional QSAR models is enabled by numerical descriptors representing the inherent chemical properties that can be easily defined for any number of molecules; however, traditional QSAR models often have limited predictive power due to the lack of data and complexity of in vivo endpoints. Although it has been indeed difficult to obtain experimentally derived toxicity data on a large number of chemicals in the past, the results of quantitative in vitro screening of thousands of environmental chemicals in hundreds of experimental systems are now available and continue to accumulate. In addition, publicly accessible toxicogenomics data collected on hundreds of chemicals provide another dimension of molecular information that is potentially useful for predictive toxicity modeling. These new characteristics of molecular bioactivity arising from short-term biological assays, i.e., in vitro screening and/or in vivo toxicogenomics data can now be exploited in combination with chemical structural information to generate hybrid QSAR–like quantitative models to predict human toxicity and carcinogenicity. Using several case studies, we illustrate the benefits of a hybrid modeling approach, namely improvements in the accuracy of models, enhanced interpretation of the most predictive features, and expanded applicability domain for wider chemical space coverage. PMID:22387746

  17. Short-chain 3-hydroxyacyl-coenzyme A dehydrogenase associates with a protein super-complex integrating multiple metabolic pathways.

    Directory of Open Access Journals (Sweden)

    Srinivas B Narayan

    Full Text Available Proteins involved in mitochondrial metabolic pathways engage in functionally relevant multi-enzyme complexes. We previously described an interaction between short-chain 3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD and glutamate dehydrogenase (GDH explaining the clinical phenotype of hyperinsulinism in SCHAD-deficient patients and adding SCHAD to the list of mitochondrial proteins capable of forming functional, multi-pathway complexes. In this work, we provide evidence of SCHAD's involvement in additional interactions forming tissue-specific metabolic super complexes involving both membrane-associated and matrix-dwelling enzymes and spanning multiple metabolic pathways. As an example, in murine liver, we find SCHAD interaction with aspartate transaminase (AST and GDH from amino acid metabolic pathways, carbamoyl phosphate synthase I (CPS-1 from ureagenesis, other fatty acid oxidation and ketogenesis enzymes and fructose-bisphosphate aldolase, an extra-mitochondrial enzyme of the glycolytic pathway. Most of the interactions appear to be independent of SCHAD's role in the penultimate step of fatty acid oxidation suggesting an organizational, structural or non-enzymatic role for the SCHAD protein.

  18. SEMICONDUCTOR INTEGRATED CIRCUITS Short locking time and low jitter phase-locked loop based on slope charge pump control

    Science.gov (United States)

    Zhongjie, Guo; Youbao, Liu; Longsheng, Wu; Xihu, Wang; Wei, Tang

    2010-10-01

    A novel structure of a phase-locked loop (PLL) characterized by a short locking time and low jitter is presented, which is realized by generating a linear slope charge pump current dependent on monitoring the output of the phase frequency detector (PFD) to implement adaptive bandwidth control. This improved PLL is created by utilizing a fast start-up circuit and a slope current control on a conventional charge pump PLL. First, the fast start-up circuit is enabled to achieve fast pre-charging to the loop filter. Then, when the output pulse of the PFD is larger than a minimum value, the charge pump current is increased linearly by the slope current control to ensure a shorter locking time and a lower jitter. Additionally, temperature variation is attenuated with the temperature compensation in the charge pump current design. The proposed PLL has been fabricated in a kind of DSP chip based on a 0.35 μm CMOS process. Comparing the characteristics with the classical PLL, the proposed PLL shows that it can reduce the locking time by 60% with a low peak-to-peak jitter of 0.3% at a wide operation temperature range.

  19. An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer

    Directory of Open Access Journals (Sweden)

    Lockwood William W

    2010-05-01

    Full Text Available Abstract Background Genomics has substantially changed our approach to cancer research. Gene expression profiling, for example, has been utilized to delineate subtypes of cancer, and facilitated derivation of predictive and prognostic signatures. The emergence of technologies for the high resolution and genome-wide description of genetic and epigenetic features has enabled the identification of a multitude of causal DNA events in tumors. This has afforded the potential for large scale integration of genome and transcriptome data generated from a variety of technology platforms to acquire a better understanding of cancer. Results Here we show how multi-dimensional genomics data analysis would enable the deciphering of mechanisms that disrupt regulatory/signaling cascades and downstream effects. Since not all gene expression changes observed in a tumor are causal to cancer development, we demonstrate an approach based on multiple concerted disruption (MCD analysis of genes that facilitates the rational deduction of aberrant genes and pathways, which otherwise would be overlooked in single genomic dimension investigations. Conclusions Notably, this is the first comprehensive study of breast cancer cells by parallel integrative genome wide analyses of DNA copy number, LOH, and DNA methylation status to interpret changes in gene expression pattern. Our findings demonstrate the power of a multi-dimensional approach to elucidate events which would escape conventional single dimensional analysis and as such, reduce the cohort sample size for cancer gene discovery.

  20. Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study

    Directory of Open Access Journals (Sweden)

    H. Ross-Adams

    2015-09-01

    Interpretation: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

  1. Detecting robust gene signature through integrated analysis of multiple types of high-throughput data in liver cancer

    Institute of Scientific and Technical Information of China (English)

    Xin-yu ZHANG; Tian-tian LI; Xiang-jun LIU

    2007-01-01

    Aim: To investigate the robust gene signature in liver cancer, we applied an integrated approach to perform a joint analysis of a highly diverse collection of liver cancer genome-wide datasets, including genomic alterations and transcrip- tion profiles. Methods: 1-class Significance Analysis of Microarrays coupled with ranking score method were used to identify the robust gene signature in liver tumor tissue. Results: In total, 1 625 051 gene expression measurements from 16 public microarrays, 2 pairs of serial analyses of gene expression experiments, and 252 loss of heterozygosity reports obtained from 568 publications were used in this integrated study. The resulting robust gene signatures included 90 genes, which may be of great importance to liver cancer research. A system assessment analysis revealed that our integrative method had an accuracy of 92% and a correlation coefficient value of 0.88. Conclusion: The system assessment results indicated that our method had the ability of integrating the datasets from various types of sources, and eliciting more accurate results, as can be very useful in the study of liver cancer.

  2. Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study

    Directory of Open Access Journals (Sweden)

    Acampa Olga

    2005-07-01

    Full Text Available Abstract Background Non-invasive diagnostic strategies aimed at identifying biomarkers of lung cancer are of great interest for early cancer detection. The aim of this study was to set up a new method for identifying and quantifying volatile organic compounds (VOCs in exhaled air of patients with non-small cells lung cancer (NSCLC, by comparing the levels with those obtained from healthy smokers and non-smokers, and patients with chronic obstructive pulmonary disease. The VOC collection and analyses were repeated three weeks after the NSCLC patients underwent lung surgery. Methods The subjects' breath was collected in a Teflon® bulb that traps the last portion of single slow vital capacity. The 13 VOCs selected for this study were concentrated using a solid phase microextraction technique and subsequently analysed by means of gas cromatography/mass spectrometry. Results The levels of the selected VOCs ranged from 10-12 M for styrene to 10-9 M for isoprene. None of VOCs alone discriminated the study groups, and so it was not possible to identify one single chemical compound as a specific lung cancer biomarker. However, multinomial logistic regression analysis showed that VOC profile can correctly classify about 80 % of cases. Only isoprene and decane levels significantly decreased after surgery. Conclusion As the combination of the 13 VOCs allowed the correct classification of the cases into groups, together with conventional diagnostic approaches, VOC analysis could be used as a complementary test for the early diagnosis of lung cancer. Its possible use in the follow-up of operated patients cannot be recommended on the basis of the results of our short-term nested study.

  3. Integration

    DEFF Research Database (Denmark)

    Emerek, Ruth

    2004-01-01

    Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration......Bidraget diskuterer de forskellige intergrationsopfattelse i Danmark - og hvad der kan forstås ved vellykket integration...

  4. Prediction of the efficacy of immunotherapy by measuring the integrity of cell-free DNA in plasma in colorectal cancer.

    Science.gov (United States)

    Kitahara, Masahiro; Hazama, Shoichi; Tsunedomi, Ryouichi; Takenouchi, Hiroko; Kanekiyo, Shinsuke; Inoue, Yuka; Nakajima, Masao; Tomochika, Shinobu; Tokuhisa, Yoshihiro; Iida, Michihisa; Sakamoto, Kazuhiko; Suzuki, Nobuaki; Takeda, Shigeru; Ueno, Tomio; Yamamoto, Shigeru; Yoshino, Shigefumi; Nagano, Hiroaki

    2016-12-01

    We previously reported a phase II study of a cancer vaccine using five novel peptides recognized by HLA-A*2402-restricted CTL in combination with oxaliplatin-containing chemotherapy (FXV study) as first-line therapy for patients with metastatic colorectal cancer and demonstrated the safety and promising potential of our five-peptide cocktail. The objective of this analysis was to identify predictive biomarkers for identifying patients who are likely to receive a clinical benefit from immunochemotherapy. Circulating cell-free DNA (cfDNA) in plasma has been reported to be a candidate molecular biomarker for the efficacy of anticancer therapy. Unlike uniformly truncated small-sized DNA released from apoptotic normal cells, DNA released from necrotic cancer cells varies in size. The integrity of plasma cfDNA (i.e. the ratio of longer fragments [400 bp] to shorter fragments [100 bp] of cfDNA), may be clinically useful for detecting colorectal cancer progression. We assessed plasma samples collected from 93 patients prior to receiving immunochemotherapy. The cfDNA levels and integrity were analyzed by semi-quantitative real-time PCR. Progression-free survival was significantly better in patients with a low plasma cfDNA integrity value than in those with a high value (P = 0.0027). Surprisingly, in the HLA-A*2402-matched group, patients with a low plasma cfDNA integrity value had significantly better progression-free survival than those with a high value (P = 0.0015). This difference was not observed in the HLA-A*2402-unmatched group. In conclusion, the integrity of plasma cfDNA may provide important clinical information and may be a useful predictive biomarker of the outcome of immunotherapy in metastatic colorectal cancer.

  5. INTEGRAL/IBIS observations of the Galactic center region at the epoch of the short Fermi/LAT flare

    DEFF Research Database (Denmark)

    Fiocchi, M.; Sanchez-Fernandez, C.; Natalucci, L.;

    2011-01-01

    was reported. SAX J1747.0-2853 was not detected in the IBIS/ISGRI images produced in the range 20-60 keV and we find 3 sigma upper limits of 6 mCrab for period (a) and 4 mCrab for period (b). Conversely, during a 10.4 ks period including the XRT observation, we have an indication of faint activity......The Galactic Center was in the IBIS/ISGRI field-of-view during the epoch of the gamma-ray flare observed recently by Fermi/LAT (ATEL#3162). During the 20s interval of the flare IBIS/ISGRI did not detect any emission from SAX J1747.0-2853, located at ~10degrees off-axis, with a 3sigma upper limit...... of ~250mCrab in the 20-60 keV band. We have also analyzed two separate time slots of 6 and 7 pointings, respectively: (a) 2011 Feb. 10, 11:41-18:41 UT, and (b) 2011 Feb. 12, 04:09-10:09 UT. The retrieved data belong to the near-real time INTEGRAL archive. The first period includes the gamma-ray flare...

  6. Impact of single-point GPS integrated water vapor estimates on short-range WRF model forecasts over southern India

    Science.gov (United States)

    Kumar, Prashant; Gopalan, Kaushik; Shukla, Bipasha Paul; Shyam, Abhineet

    2016-09-01

    Specifying physically consistent and accurate initial conditions is one of the major challenges of numerical weather prediction (NWP) models. In this study, ground-based global positioning system (GPS) integrated water vapor (IWV) measurements available from the International Global Navigation Satellite Systems (GNSS) Service (IGS) station in Bangalore, India, are used to assess the impact of GPS data on NWP model forecasts over southern India. Two experiments are performed with and without assimilation of GPS-retrieved IWV observations during the Indian winter monsoon period (November-December, 2012) using a four-dimensional variational (4D-Var) data assimilation method. Assimilation of GPS data improved the model IWV analysis as well as the subsequent forecasts. There is a positive impact of ˜10 % over Bangalore and nearby regions. The Weather Research and Forecasting (WRF) model-predicted 24-h surface temperature forecasts have also improved when compared with observations. Small but significant improvements were found in the rainfall forecasts compared to control experiments.

  7. Usefulness of Integrated PET/MRI in Head and Neck Cancer: A Preliminary Study

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Soo Jin; Seo, Hyo Jung; Cheon, Gi Jeong; Kim, Ji Hoon; Kim, E. Edmund; Kang, Keon Wook; Paeng, Jin Chul; Chung, Junekey; Lee, Dong Soo [Seoul National Univ., Seoul (Korea, Republic of)

    2014-06-15

    The new modality of an integrated positron emission tomography/magnetic resonance imaging (PET/MRI) has recently been introduced but not validated. Our objective was to evaluate clinical performance of {sup 18}F-fluoro-2-deoxyglucose ({sup 18}F-FDG) PET/MRI in patients with head and neck cancer. This retrospective study was conducted between January 2013 and February 2013. Ten patients (eight men, two women; mean age, 61.4±13.4 years) with histologically proven head and neck tumors were enrolled.Whole-body PET/MRI and regional positron emission tomography (PET) with dedicated MRI were sequentially obtained. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume, total lesion glycolysis and contrast enhancement were analyzed. A total of ten whole-body positron emission tomography (PET), ten regional positron emission tomography (PET), ten dedicated MRI and ten regional PET/gadolinium-enhanced T1-weighted (Gd)-MRI images were analyzed for initial staging. Two nuclear medicine physicians analyzed positron emission tomography (PET) and PET/MRI with a consensus. One radiologist analyzed dedicated MRI. The primary lesions and number of metastatic lymph nodes analyzed from each image were compared. Eight patients were diagnosed with head and neck cancer (one tongue cancer, four tonsillar cancers, one nasopharyngeal cancer and two hypopharyngeal cancers) by histological diagnosis. Two benign tumors (pleomorphic adenoma and Warthin tumor) were diagnosed with surgical operation. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) attenuated by MRI showed good image quality for the lesion detection. Whole-body positron emission tomography (PET) and regional positron emission tomography (PET) detected ten primary sites and compensated for a missed lesion on dedicated MRI. A discordant number of suspicious lymph node metastases was noted according to the different images; 22, 16, 39 and 40 in the whole

  8. Results of Neoadjuvant Short-Course Radiation Therapy Followed by Transanal Endoscopic Microsurgery for T1-T2 N0 Extraperitoneal Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Arezzo, Alberto, E-mail: alberto.arezzo@unito.it [General Surgery I, Department of Surgical Sciences, University of Torino, Torino (Italy); Arolfo, Simone; Allaix, Marco Ettore [General Surgery I, Department of Surgical Sciences, University of Torino, Torino (Italy); Munoz, Fernando [Radiation Oncology, Department of Oncology, University of Torino, Torino (Italy); Cassoni, Paola [Pathology Unit, Department of Medical Sciences, University of Torino, Torino (Italy); Monagheddu, Chiara [Clinical Epidemiology Unit, Piedmont Reference Centre for Epidemiology and Cancer Prevention, City of Health and Science Hospital of Torino, Torino (Italy); Ricardi, Umberto [Radiation Oncology, Department of Oncology, University of Torino, Torino (Italy); Ciccone, Giovannino [Clinical Epidemiology Unit, Piedmont Reference Centre for Epidemiology and Cancer Prevention, City of Health and Science Hospital of Torino, Torino (Italy); Morino, Mario [General Surgery I, Department of Surgical Sciences, University of Torino, Torino (Italy)

    2015-06-01

    Purpose: This study was undertaken to assess the short-term outcomes of neoadjuvant short-course radiation therapy (SCRT) followed by transanal endoscopic microsurgery (TEM) for T1-T2 N0 extraperitoneal rectal cancer. Recent studies suggest that neoadjuvant radiation therapy followed by TEM is safe and has results similar to those with abdominal rectal resection for the treatment of extraperitoneal early rectal cancer. Methods and Materials: We planned a prospective pilot study including 25 consecutive patients with extraperitoneal T1-T2 N0 M0 rectal adenocarcinoma undergoing SCRT followed by TEM 4 to 10 weeks later (SCRT-TEM). Safety, efficacy, and acceptability of this treatment modality were compared with historical groups of patients with similar rectal cancer stage and treated with long-course radiation therapy (LCRT) followed by TEM (LCRT-TEM), TEM alone, or laparoscopic rectal resection with total mesorectal excision (TME) at our institution. Results: The study was interrupted after 14 patients underwent SCRT of 25 Gy in 5 fractions followed by TEM. Median time between SCRT and TEM was 7 weeks (range: 4-10 weeks). Although no preoperative complications occurred, rectal suture dehiscence was observed in 7 patients (50%) at 4 weeks follow-up, associated with an enterocutaneous fistula in the sacral area in 2 cases. One patient required a colostomy. Quality of life at 1-month follow-up, according to European Organization for Research and Treatment of Cancer QLQ-C30 survey score, was significantly worse in SCRT-TEM patients than in LCRT-TEM patients (P=.0277) or TEM patients (P=.0004), whereas no differences were observed with TME patients (P=.604). At a median follow-up of 10 months (range: 6-26 months), we observed 1 (7%) local recurrence at 6 months that was treated with abdominoperineal resection. Conclusions: SCRT followed by TEM for T1-T2 N0 rectal cancer is burdened by a high rate of painful dehiscence of the suture line and enterocutaneous

  9. Response to Dr Stevens' letter ref. Visitisen et al: "Short-term effects of night shift work on breast cancer risk: a cohort study of payroll data".

    Science.gov (United States)

    Kolstad, Henrik A; Garde, Anne Helene; Hansen, Åse Marie; Frydenberg, Morten; Christiansen, Peer; Vistisen, Helene Tilma; Bonde, Jens Peter E

    2017-01-01

    selection bias, but we observed similar risk estimates as for the total study population. Taken together, we find that our study provides rather robust evidence of no short-term breast cancer risk following recent night shift work. It must, however, be stressed that data did not allow assessment of a possible long-term risk. Reference 1. Stevens R. Letter ref. Vitisen et al: "Short-term effects of night shift work on breast cancer risk: a cohort study of payroll data". Scand J Work Environ Health. 2017;43(1):95. http://dx.doi.org/10.5271/sjweh.3607 2. Vistisen HT, Garde AH, Frydenberg M, Christiansen P, Hansen AM, Hansen J, Bonde JP, Kolstad HA. Short-term effects of night shift work on breast cancer risk: A cohort study of payroll data. Scand J Work Environ Health. 2017;43(1):59-67. http://dx.doi.org/10.5271/sjweh.3603. 3. Ijaz S, Verbeek J, Seidler A, Lindbohm ML, Ojajarvi A, Orsini N, Costa G, Neuvonen K. Night-shift work and breast cancer--a systematic review and meta-analysis. Scand J Work Environ Health. 2013 Sep 1;39(5):431-47. http://dx.doi.org/10.5271/sjweh.3371.

  10. A Randomized Trial (Irish Clinical Oncology Research Group 97-01) Comparing Short Versus Protracted Neoadjuvant Hormonal Therapy Before Radiotherapy for Localized Prostate Cancer.

    LENUS (Irish Health Repository)

    Armstrong, John G

    2010-08-24

    PURPOSE: To examine the long-term outcomes of a randomized trial comparing short (4 months; Arm 1) and long (8 months; Arm 2) neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer. METHODS AND MATERIALS: Between 1997 and 2001, 276 patients were enrolled and the data from 261 were analyzed. The stratification risk factors were prostate-specific antigen level >20 ng\\/mL, Gleason score >\\/=7, and Stage T3 or more. The intermediate-risk stratum had one factor and the high-risk stratum had two or more. Staging was done from the bone scan and computed tomography findings. The primary endpoint was biochemical failure-free survival. RESULTS: The median follow-up was 102 months. The overall survival, biochemical failure-free survival. and prostate cancer-specific survival did not differ significantly between the two treatment arms, overall or at 5 years. The cumulative probability of overall survival at 5 years was 90% (range, 87-92%) in Arm 1 and 83% (range, 80-86%) in Arm 2. The biochemical failure-free survival rate at 5 years was 66% (range, 62-71%) in Arm 1 and 63% (range, 58-67%) in Arm 2. CONCLUSION: No statistically significant difference was found in biochemical failure-free survival between 4 months and 8 months of neoadjuvant hormonal therapy before radiotherapy for localized prostate cancer.

  11. Modulatory effects of heparin and short-length oligosaccharides of heparin on the metastasis and growth of LMD MDA-MB 231 breast cancer cells in vivo.

    Science.gov (United States)

    Mellor, P; Harvey, J R; Murphy, K J; Pye, D; O'Boyle, G; Lennard, T W J; Kirby, J A; Ali, S

    2007-09-17

    Expression of the chemokine receptor CXCR4 allows breast cancer cells to migrate towards specific metastatic target sites which constitutively express CXCL12. In this study, we determined whether this interaction could be disrupted using short-chain length heparin oligosaccharides. Radioligand competition binding assays were performed using a range of heparin oligosaccharides to compete with polymeric heparin or heparan sulphate binding to I(125) CXCL12. Heparin dodecasaccharides were found to be the minimal chain length required to efficiently bind CXCL12 (71% inhibition; PLMD MDA-MB 231 breast cancer cells. In addition, heparin dodecasaccharides were found to have less anticoagulant activity than either a smaller quantity of polymeric heparin or a similar amount of the low molecular weight heparin pharmaceutical product, Tinzaparin. When given subcutaneously in a SCID mouse model of human breast cancer, heparin dodecasaccharides had no effect on the number of lung metastases, but did however inhibit (P<0.05) tumour growth (lesion area) compared to control groups. In contrast, polymeric heparin significantly inhibited both the number (P<0.001) and area of metastases, suggesting a differing mechanism for the action of polymeric and heparin-derived oligosaccharides in the inhibition of tumour growth and metastases.

  12. Short-Term Outcomes and Safety of Computed Tomography-Guided Percutaneous Microwave Ablation of Solitary Adrenal Metastasis from Lung Cancer: A Multi-Center Retrospective Study

    Science.gov (United States)

    Men, Min; Fan, Weijun; Zhang, Kaixian; Bi, Jingwang; Yang, Xia; Zheng, Aimin; Huang, Guanghui; Wei, Zhigang

    2016-01-01

    Objective To retrospectively evaluate the short-term outcomes and safety of computed tomography (CT)-guided percutaneous microwave ablation (MWA) of solitary adrenal metastasis from lung cancer. Materials and Methods From May 2010 to April 2014, 31 patients with unilateral adrenal metastasis from lung cancer who were treated with CT-guided percutaneous MWA were enrolled. This study was conducted with approval from local Institutional Review Board. Clinical outcomes and complications of MWA were assessed. Results Their tumors ranged from 1.5 to 5.4 cm in diameter. After a median follow-up period of 11.1 months, primary efficacy rate was 90.3% (28/31). Local tumor progression was detected in 7 (22.6%) of 31 cases. Their median overall survival time was 12 months. The 1-year overall survival rate was 44.3%. Median local tumor progression-free survival time was 9 months. Local tumor progression-free survival rate was 77.4%. Of 36 MWA sessions, two (5.6%) had major complications (hypertensive crisis). Conclusion CT-guided percutaneous MWA may be fairly safe and effective for treating solitary adrenal metastasis from lung cancer. PMID:27833402

  13. Disruption of human papillomavirus 16 E6 gene by clustered regularly interspaced short palindromic repeat/Cas system in human cervical cancer cells

    Directory of Open Access Journals (Sweden)

    Yu L

    2014-12-01

    Full Text Available Lan Yu, Xiaoli Wang, Da Zhu, Wencheng Ding, Liming Wang, Changlin Zhang, Xiaohui Jiang, Hui Shen, Shujie Liao, Ding Ma, Zheng Hu, Hui Wang Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China Abstract: High-risk human papillomavirus (HPV, especially HPV16, is considered a main causative agent of cervical cancer. Upon HPV infection, the viral oncoprotein E6 disrupts the host tumor-suppressor protein p53, thus promoting malignant transformation of normal cervical cells. Here, we used the newly developed programmable ribonucleic acid-guided clustered regularly interspaced short palindromic repeat (CRISPR/Cas system to disrupt the HPV16 E6 gene. We showed that HPV16 E6 deoxyribonucleic acid was cleaved at specific sites, leading to apoptosis and growth inhibition of HPV16-positive SiHa and CaSki cells, but not HPV-negative C33A or human embryonic kidney 293 cells. We also observed downregulation of the E6 protein and restoration of the p53 protein. These data proved that the HPV16 E6 ribonucleic acid-guided CRISPR/Cas system might be an effective therapeutic agent in treating HPV infection-related cervical malignancy. Keywords: CRISPR/Cas system, E6, p53, SiHa, CaSki, cervical cancer

  14. Breast cancer osteomimicry and its role in bone specific metastasis; an integrative, systematic review of preclinical evidence.

    Science.gov (United States)

    Awolaran, Olugbenga; Brooks, Susan A; Lavender, Verna

    2016-12-01

    Metastasis accounts for most of the deaths from breast cancer and the preference of invasive breast cancer metastasising to bone has been widely reported. However, the biological basis of breast cancer osteotropism is not fully understood. This paper provides, for the first time, an integrative, systematic review of evidence of molecular factors that have functional roles in the homing of metastatic breast cancer to the bone. Pubmed, Web of Science and EBSCOhost were searched using keywords and synonyms for molecular, metastasis, breast cancer and bone to identify articles published between January 2004 and August 2016. 4491 potentially relevant citations were retrieved. 63 articles met the inclusion criteria, which were primary studies reporting evidence of molecular factors that have functional roles in predisposing breast cancer bone metastasis in vivo. 12 of those 63 articles that additionally met quality criteria were included in the review. Extracted data were tabulated and key findings that indicated biological mechanisms involved in breast cancer metastasis to bone were synthesised. 15 proteins expressed by breast cancer cells were identified as factors that mediate breast cancer bone metastasis: ICAM-1, cadherin-11, osteoactivin, bone sialoprotein, CCN3, IL-11, CCL2, CITED2, CXCR4, CTGF, OPN, CX3CR1, TWIST1, adrenomedullin and Enpp1. Upregulation or overexpression of one or more of them by breast cancer cells resulted in increased breast cancer metastasis to bone in vivo, except for CCL2 where bone-metastatic cells showed a reduced expression of this factor. All factors identified, here expressed by breast cancer cells, are proteins that are normally expressed in the bone microenvironment and linked to physiologic bone functions. All have a functional role in one of more of the following: cell proliferation and differentiation, bone mineralization and remodelling, cell adhesion and/or chemokine signalling. Six of them (cadherin-11, ICAM-1, OPN, CX3CR1

  15. Intravenous Mistletoe Treatment in Integrative Cancer Care: A Qualitative Study Exploring the Procedures, Concepts, and Observations of Expert Doctors

    Directory of Open Access Journals (Sweden)

    Gunver S. Kienle

    2016-01-01

    Full Text Available Background. Mistletoe therapy (MT is widely used in patient-centered integrative cancer care. The objective of this study was to explore the concepts, procedures, and observations of expert doctors, with a focus on intravenous MT. Method. A qualitative interview study was conducted with 35 highly experienced doctors specialized in integrative and anthroposophic medicine. Structured qualitative content analysis was applied. For triangulation, the results were compared with external evidence that was systematically collected, reviewed, and presented. Results. Doctors perform individualized patient assessments that lead to multimodal treatment approaches. The underlying goal is to help patients to live with and overcome disease. Mistletoe infusions are a means of accomplishing this goal. They are applied to stabilize disease, achieve responsiveness, induce fever, improve quality of life, and improve the tolerability of conventional cancer treatments. The doctors reported long-term disease stability and improvements in patients’ general condition, vitality, strength, thermal comfort, appetite, sleep, pain from bone metastases, dyspnea in pulmonary lymphangitis carcinomatosa, fatigue, and cachexia; chemotherapy was better tolerated. Also patients’ emotional and mental condition was reported to have improved. Conclusion. Individualized integrative cancer treatment including MT aims to help cancer patients to live well with their disease. Further research should investigate the reported observations.

  16. Short-term outcome in patients treated with cytoreduction and HIPEC compared to conventional colon cancer surgery

    DEFF Research Database (Denmark)

    Simkens, Geert A; Verwaal, Victor Jilbert; Lemmens, Valery E;

    2016-01-01

    peritoneally metastasized (PM) colon cancer patients treated with CRS + HIPEC and patients undergoing conventional colon surgery. Furthermore, the impact of CRS + HIPEC on the risk of postoperative complications will be assessed, probably leading to better insight into how to report on postoperative outcomes...... in this distinct group of patients undergoing extensive colon surgery.All patients with primary colon cancer who underwent segmental colon resection in a tertiary referral hospital between 2011 and 2014 were included in this prospective cohort study. Outcome after surgery was compared between patients who......-related mortality.Although patients with colonic PM undergoing CRS + HIPEC treatment were younger and healthier, the postoperative outcome was worse. This is most probably due to less favorable tumor characteristics and more extensive surgery. Nevertheless, CRS + HIPEC treatment was not associated with severe...

  17. High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients

    DEFF Research Database (Denmark)

    Nielsen, Boye Schnack; Jørgensen, Stine; Fog, Jacob Ulrik;

    2011-01-01

    relative to the nuclear density (TBR) obtained using a red nuclear stain. High TBR (and TB) estimates of miR-21 expression correlated significantly with shorter disease-free survival (p = 0.004, HR = 1.28, 95% CI: 1.06-1.55) in the stage II colon cancer patient group, whereas no significant correlation......Approximately 25% of all patients with stage II colorectal cancer will experience recurrent disease and subsequently die within 5 years. MicroRNA-21 (miR-21) is upregulated in several cancer types and has been associated with survival in colon cancer. In the present study we developed a robust......R-21 signal was revealed as a blue chromogenic reaction, predominantly observed in fibroblast-like cells located in the stromal compartment of the tumors. The expression levels were measured using image analysis. The miR-21 signal was determined as the total blue area (TB), or the area fraction...

  18. Microfluidics & nanotechnology: Towards fully integrated analytical devices for the detection of cancer biomarkers

    KAUST Repository

    Perozziello, Gerardo

    2014-01-01

    In this paper, we describe an innovative modular microfluidic platform allowing filtering, concentration and analysis of peptides from a complex mixture. The platform is composed of a microfluidic filtering device and a superhydrophobic surface integrating surface enhanced Raman scattering (SERS) sensors. The microfluidic device was used to filter specific peptides (MW 1553.73 D) derived from the BRCA1 protein, a tumor-suppressor molecule which plays a pivotal role in the development of breast cancers, from albumin (66.5 KD), the most represented protein in human plasma. The filtering process consisted of driving the complex mixture through a porous membrane having a cut-off of 12-14 kD by hydrodynamic flow. The filtered samples coming out of the microfluidic device were subsequently deposited on a superhydrophobic surface formed by micro pillars on top of which nanograins were fabricated. The nanograins coupled to a Raman spectroscopy instrument acted as a SERS sensor and allowed analysis of the filtered sample on top of the surface once it evaporated. By using the presented platform, we demonstrate being able to sort small peptides from bigger proteins and to detect them by using a label-free technique at a resolution down to 0.1 ng μL-1. The combination of microfluidics and nanotechnology to develop the presented microfluidic platform may give rise to a new generation of biosensors capable of detecting low concentration samples from complex mixtures without the need for any sample pretreatment or labelling. The developed devices could have future applications in the field of early diagnosis of severe illnesses, e.g. early cancer detection. This journal is

  19. Helical tomotherapy in cervical cancer patients. Simultaneous integrated boost concept: technique and acute toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Marnitz, Simone; Stromberger, Carmen; Kawgan-Kagan, Michael; Wlodarczyk, Waldemar; Jahn, Ulrich; Budach, Volker [Dept. of Radiooncology, Charite - Univ. Medicine, Berlin (Germany); Schneider, Achim; Koehler, Christhardt [Dept. of Gynecology Charite - Univ. Medicine, Berlin (Germany); Ulrich, Uwe [Dept. of Gynecology and Obstetrics, Martin Luther Hospital, Berlin (Germany)

    2010-10-15

    Purpose: To evaluate the acute toxicity of simultaneous integrated boost (SIB) technique for dose escalation with helical tomotherapy (HT) in patients with locally advanced cervical cancer. Patients and Methods: 20 patients (FIGO IB1 pN1-IIIB) underwent primary chemoradiation. Prior to chemoradiation, a laparoscopic pelvic and para-aortic lymphadenectomy was performed. A boost region was defined using titanium clips during staging for planning target volume (PTV-B). Patients were treated with five weekly fractions of 1.8 Gy to a total dose of 50.4 Gy to the tumor region and the pelvic (para-aortic) lymph node region (PTV-A), and five weekly fractions of 2.12 Gy to a total dose of 59.36 Gy to the PTV-B. Chemotherapy consisted of weekly cisplatin 40 mg/m{sup 2}. 19 patients underwent brachytherapy. Dose-volume histograms were evaluated and acute gastrointestinal (GI), genitourinary (GU), and hematologic toxicity were documented (CTCAE v3.0). Results: Pelvic and para-aortic lymph node metastases were confirmed in nine and four patients, respectively. Five patients refused laparoscopic staging. The mean volume of PTV-A and PTV-B was 1,570 {+-} 404 cm{sup 3} and 341 {+-} 125 cm{sup 3}, respectively. The mean dose to the bladder, rectum, and small bowel was 47.85 Gy, 45.76 Gy, and 29.71 Gy, respectively. No grade 4/5 toxicity was observed. Grade 2/3 hematologic toxicity occurred in 50% of patients and 5% experienced grade 3 diarrhea. There was no grade 3 GU toxicity. 19 patients underwent curettage 6-9 weeks after chemoradiation without any evidence of tumor. Conclusion: The concept of SIB for dose escalation in patients with locally advanced cervical cancer is feasible with a low rate of acute toxicity. Whether dose escalation can translate into improved outcome will be assessed after a longer follow-up. (orig.)

  20. Integrated analysis of differentially expressed genes and pathways in triple-negative breast cancer

    Science.gov (United States)

    Peng, Cancan; Ma, Wenli; Xia, Wei; Zheng, Wenling

    2017-01-01

    Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by an aggressive phenotype and reduced survival. The aim of the present study was to investigate the molecular mechanisms involved in the carcinogenesis of TNBC and to identify novel target molecules for therapy. The differentially expressed genes (DEGs) in TNBC and normal adjacent tissue were assessed by analyzing the GSE41970 microarray data using Qlucore Omics Explorer, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes. Pathway enrichment analyses for DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery online resource. A protein-protein interaction (PPI) network was constructed using Search Tool for the Retrieval of Interacting Genes, and subnetworks were analyzed by ClusterONE. The PPI network and subnetworks were visualized using Cytoscape software. A total of 121 DEGs were obtained, of which 101 were upregulated and 20 were downregulated. The upregulated DEGs were significantly enriched in 14 pathways and 83 GO biological processes, while the downregulated DEGs were significantly enriched in 18 GO biological processes. The PPI network with 118 nodes and 1,264 edges was constructed and three subnetworks were extracted from the entire network. The significant hub DEGs with high degrees were identified, including TP53, glyceraldehyde-3-phosphate dehydrogenase, cyclin D1, HRAS and proliferating cell nuclear antigen, which were predominantly enriched in the cell cycle pathway and pathways in cancer. A number of critical genes and pathways were revealed to be associated with TNBC. The present study may provide an improved understanding of the pathogenesis of TNBC and contribute to the development of therapeutic targets for TNBC. PMID:28075450

  1. Dose-escalated simultaneous integrated-boost treatment of prostate cancer patients via helical tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Geier, M.; Astner, S.T.; Duma, M.N.; Putzhammer, J.; Winkler, C.; Molls, M.; Geinitz, H. [Technische Univ. Muenchen (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie; Jacob, V. [Universitaetsklinikum Freiburg (Germany). Klinik fuer Strahlenheilkunde; Nieder, C. [Nordland Hospital, Bodoe (Norway). Dept. of Oncology and Palliative Care; Tromsoe Univ. (Norway). Inst. of Clinical Medicine

    2012-05-15

    The goal of this work was to assess the feasibility of moderately hypofractionated simultaneous integrated-boost intensity-modulated radiotherapy (SIB-IMRT) with helical tomotherapy in patients with localized prostate cancer regarding acute side effects and dose-volume histogram data (DVH data). Acute side effects and DVH data were evaluated of the first 40 intermediate risk prostate cancer patients treated with a definitive daily image-guided SIB-IMRT protocol via helical tomotherapy in our department. The planning target volume including the prostate and the base of the seminal vesicles with safety margins was treated with 70 Gy in 35 fractions. The boost volume containing the prostate and 3 mm safety margins (5 mm craniocaudal) was treated as SIB to a total dose of 76 Gy (2.17 Gy per fraction). Planning constraints for the anterior rectal wall were set in order not to exceed the dose of 76 Gy prescribed to the boost volume. Acute toxicity was evaluated prospectively using a modified CTCAE (Common Terminology Criteria for Adverse Events) score. SIB-IMRT allowed good rectal sparing, although the full boost dose was permitted to the anterior rectal wall. Median rectum dose was 38 Gy in all patients and the median volumes receiving at least 65 Gy (V65), 70 Gy (V70), and 75 Gy (V75) were 13.5%, 9%, and 3%, respectively. No grade 4 toxicity was observed. Acute grade 3 toxicity was observed in 20% of patients involving nocturia only. Grade 2 acute intestinal and urological side effects occurred in 25% and 57.5%, respectively. No correlation was found between acute toxicity and the DVH data. This institutional SIB-IMRT protocol using daily image guidance as a precondition for smaller safety margins allows dose escalation to the prostate without increasing acute toxicity. (orig.)

  2. Integrative genomic data mining for discovery of potential blood-borne biomarkers for early diagnosis of cancer.

    Directory of Open Access Journals (Sweden)

    Yongliang Yang

    Full Text Available BACKGROUND: With the arrival of the postgenomic era, there is increasing interest in the discovery of biomarkers for the accurate diagnosis, prognosis, and early detection of cancer. Blood-borne cancer markers are favored by clinicians, because blood samples can be obtained and analyzed with relative ease. We have used a combined mining strategy based on an integrated cancer microarray platform, Oncomine, and the biomarker module of the Ingenuity Pathways Analysis (IPA program to identify potential blood-based markers for six common human cancer types. METHODOLOGY/PRINCIPAL FINDINGS: In the Oncomine platform, the genes overexpressed in cancer tissues relative to their corresponding normal tissues were filtered by Gene Ontology keywords, with the extracellular environment stipulated and a corrected Q value (false discovery rate cut-off implemented. The identified genes were imported to the IPA biomarker module to separate out those genes encoding putative secreted or cell-surface proteins as blood-borne (blood/serum/plasma cancer markers. The filtered potential indicators were ranked and prioritized according to normalized absolute Student t values. The retrieval of numerous marker genes that are already clinically useful or under active investigation confirmed the effectiveness of our mining strategy. To identify the biomarkers that are unique for each cancer type, the upregulated marker genes that are in common between each two tumor types across the six human tumors were also analyzed by the IPA biomarker comparison function. CONCLUSION/SIGNIFICANCE: The upregulated marker genes shared among the six cancer types may serve as a molecular tool to complement histopathologic examination, and the combination of the commonly upregulated and unique biomarkers may serve as differentiating markers for a specific cancer. This approach will be increasingly useful to discover diagnostic signatures as the mass of microarray data continues to grow in the

  3. Integrating Enzymatic Self-Assembly and Mitochondria Targeting for Selectively Killing Cancer Cells without Acquired Drug Resistance.

    Science.gov (United States)

    Wang, Huaimin; Feng, Zhaoqianqi; Wang, Youzhi; Zhou, Rong; Yang, Zhimou; Xu, Bing

    2016-12-14

    Targeting organelles by modulating the redox potential of mitochondria is a promising approach to kill cancer cells that minimizes acquired drug resistance. However, it lacks selectivity because mitochondria perform essential functions for (almost) all cells. We show that enzyme-instructed self-assembly (EISA), a bioinspired molecular process, selectively generates the assemblies of redox modulators (e.g., triphenyl phosphinium (TPP)) in the pericellular space of cancer cells for uptake, which allows selectively targeting the mitochondria of cancer cells. The attachment of TPP to a pair of enantiomeric, phosphorylated tetrapeptides produces the precursors (L-1P or D-1P) that form oligomers. Upon dephosphorylation catalyzed by ectophosphatases (e.g., alkaline phosphatase (ALP)) overexpressed on cancer cells (e.g., Saos2), the oligomers self-assemble to form nanoscale assemblies only on the surface of the cancer cells. The cancer cells thus uptake these assemblies of TPP via endocytosis, mainly via a caveolae/raft-dependent pathway. Inside the cells, the assemblies of TPP-peptide conjugates escape from the lysosome, induce dysfunction of mitochondria to release cytochrome c, and result in cell death, while the controls (i.e., omitting TPP motif, inhibiting ALP, or removing phosphate trigger) hardly kill the Saos2 cells. Most importantly, the repeated stimulation of the cancers by the precursors, unexpectedly, sensitizes the cancer cells to the precursors. As the first example of the integration of subcellular targeting with cell targeting, this study validates the spatial control of the assemblies of nonspecific cytotoxic agents by EISA as a promising molecular process for selectively killing cancer cells without inducing acquired drug resistance.

  4. Knockdown of NAPA using short-hairpin RNA sensitizes cancer cells to cisplatin: implications to overcome chemoresistance.

    Science.gov (United States)

    Wu, Zchong-Zcho; Chao, Chuck C-K

    2010-09-15

    Cisplatin is a widely used anti-cancer drug which targets DNA in replicating cells. In the present study, we found that NAPA--a protein found in the endoplasmic reticulum (ER) and implicated in protein trafficking--protects cells against cisplatin. Accordingly, knockdown of NAPA using lentivirus-encoded shRNA (shNAPA) induced ER stress similar to cisplatin treatment in HEK293 cells. A low dose of cisplatin also elicited a mild ER stress response associated with the accumulation of the protective proteins BiP and NAPA. Remarkably, knockdown of NAPA induced apoptosis and enhanced cisplatin-induced cytotoxicity/apoptosis, thereby sensitizing cancer cells to cisplatin. On the other hand, overexpression of NAPA increased resistance to cisplatin by reducing cisplatin-induced ER stress and apoptosis. The modulatory effects of shNAPA required the tumor suppressor p53 since the effects of NAPA knockdown were reduced by the p53 inhibitor PFT-alpha and in H1299 cells which are p53-null. A partial reversal of cisplatin resistance was also observed in cisplatin-resistant HeLa cells following knockdown of NAPA. Our results also indicated that calpain is required for ER-mediated apoptosis. Importantly, combined cisplatin/shNAPA treatment suppressed tumor growth in vivo in xenograph experiments performed in nude mice. Taken together, these observations suggest that NAPA represents a target of cisplatin, and that knockdown of NAPA may improve cisplatin-based cancer therapy.

  5. The value of perfusion CT in predicting the short-term response to synchronous radiochemotherapy for cervical squamous cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiang Sheng; Fan, Hong Xia; Zhu, Hong Xian; Song, Yun Long [Air Force General Hospital of People' s Liberation Army, Department of CT, Beijing (China); Zhou, Chun Wu [Chinese Academy of Medical Sciences, Department of Radiology, Cancer Hospital, Beijing (China)

    2012-03-15

    To determine the value of the perfusion parameters in predicting short-term tumour response to synchronous radiochemotherapy for cervical squamous carcinoma. Ninety-three patients with cervical squamous carcinoma later than stage IIB were included in this study. Perfusion CT was performed for all these patients who subsequently received the same synchronous radiochemotherapy. The patients were divided into responders and non-responders according to short-term response to treatment. Baseline perfusion parameters of the two groups were compared. The perfusion parameters that might affect treatment effect were analysed by using a multivariate multi-regression analysis. The responders group had higher baseline permeability-surface area product (PS) and blood volume (BV) values than the non-responders group (P < 0.05). There was no statistical difference in baseline mean transit time (MTT) and blood flow (BF) value between the two groups (P >0.05). At multivariate multi-regression analysis, BV, PS and tumour size were significant factors in the prediction of treatment effect. Small tumours usually had high PS and BV values, and thus had a good treatment response. Perfusion CT can provide some helpful information for the prediction of the short-term effect. Synchronous radiochemotherapy may be more effective in cervical squamous carcinoma with higher baseline PS and BV. (orig.)

  6. Short-term costs of conventional vs laparoscopic assisted surgery in patients with colorectal cancer (MRC CLASICC trial)

    Science.gov (United States)

    Franks, P J; Bosanquet, N; Thorpe, H; Brown, J M; Copeland, J; Smith, A M H; Quirke, P; Guillou, P J

    2006-01-01

    The short-term clinical results of the CLASICC trial indicated that clinical outcomes were similar between laparoscopic and open approaches. This study presents the short-term (3 month) cost analysis undertaken on a subset of patients entered into the CLASICC trial (682 of 794 patients). As expected the costs associated with the operation were higher in the 452 patients randomised to laparoscopic surgery (lap) compared with the 230 randomised to open procedure (open), £1703 vs £1386. This was partially offset by the other hospital (nontheatre) costs, which were lower in the lap group (£2930 vs £3176). The average cost to individuals for reoperations was higher in the lap group (£762 vs £553). Overall costs were slightly higher in the lap group (£6899 vs £6631), with mean difference of £268 (95%CI −689 to 1457). Sensitivity analysis made little difference to these results. The cost of rectal surgery was higher than for colon, for lap (£8259 vs £5586) and open procedures (£7820 vs £5503). The short-term cost analysis for the CLASICC trial indicates that the costs of either laparoscopic or open procedure were similar, lap surgery costing marginally more on average than open surgery. PMID:16755298

  7. Short-term Survival of Patients with Lung Metastases from Colorectal and Non-colorectal Cancer Who Underwent Pulmonary Metastasectomy.

    Science.gov (United States)

    Lumachi, Franco; Mazza, Francesco; Del Conte, Alessandro; Lo Re, Giovanni; Ermani, Mario; Chiara, Giordano B; Basso, Stefano M M

    2015-06-01

    The lung is a common site of metastases, whose prevalence varies as a function of the primary tumor site, which is usually colorectal cancer (CRC), breast carcinoma, or genitourinary cancers, such as ovary, urinary bladder and renal cell carcinomas. The aim of the present study was to analyze whether the site of primitive tumor affects overall survival (OS) of patients with lung metastases (LMs) who underwent pulmonary metastasectomy. The data of 41 patients with surgically treated CRC (Group A=22 patients) and non-colorectal carcinomas (Group B=19 patients), who developed matachronous LMs and underwent pulmonary metastasectomy with curative intent, were analyzed. The origin of non-colorectal LMs was genitourinary cancer in nine and breast cancer in 10 patients. Overall, there were 22 men and 19 women, with a median age of 65 years (range=31-80); 18 patients had a solitary metastatic tumor, while 23 had two or more LMs. Twenty-nine patients underwent wedge resection, through thoracotomy or video-assisted thoracic surgery, while 12 underwent pulmonary lobectomy. Seventy-five LMs were resected with a 5-tear OS of 48.8%. No difference was found between elderly (≥65 year-old) and younger patients (p=0.26), and between those with solitary or multiple LMs (p=0.62) in terms of survival rate. The female patients had a worse OS (31.6% vs. 63.6%; odds ratio (OR)=3.79, 95% confidence interval (CI)=1.03-13.91, p=0.003) compared to males, independent of the origin of primary cancer. There was no difference in the cumulative survival rates (OR=1.65, 95%CI=0.48-5.69, p=0.42) between Groups and the log-rank test (p=0.75) was not significant. In conclusion, the main pathological characteristics of metastatic lesions and advanced age do not appear to be associated with a poor prognosis in patients with LMs, while the female gender is a negative prognostic factor. Thus, the primary tumor site should not be considered a major criterion in selecting patients for pulmonary

  8. Integrated PET/MRI for whole-body staging of patients with primary cervical cancer: preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Grueneisen, Johannes; Kinner, Sonja; Forsting, Michael; Lauenstein, Thomas; Umutlu, Lale [University Hospital Essen, University of Duisburg-Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany); Schaarschmidt, Benedikt Michael [University Hospital Dusseldorf, University of Dusseldorf, Department of Diagnostic and Interventional Radiology, Dusseldorf (Germany); Heubner, Martin; Aktas, Bahriye [University Hospital Essen, University of Duisburg-Essen, Department of Obstetrics and Gynecology, Essen (Germany); Ruhlmann, Verena [University Hospital Essen, University of Duisburg-Essen, Department of Nuclear Medicine, Essen (Germany)

    2015-11-15

    To assess the diagnostic value of integrated PET/MRI for whole-body staging of cervical cancer patients, as well as to investigate a potential association between PET/MRI derived functional parameters and prognostic factors of cervical cancer. The present study was approved by the local institutional review board. Twenty-seven patients with histopathologically confirmed cervical cancer were prospectively enrolled in our study. All patients underwent a whole-body PET/MRI examination after written informed consent was obtained. Two radiologists separately evaluated the PET/MRI data sets regarding the determination of local tumor extent of primary cervical cancer lesions, as well as detection of nodal and distant metastases. Furthermore, SUV and ADC values of primary tumor lesions were analyzed and correlated with dedicated prognostic factors of cervical cancer. Results based on histopathology and cross-sectional imaging follow-up served as the reference standard. PET/MRI enabled the detection of all 27 primary tumor lesions of the uterine cervix and allowed for the correct determination of the T-stage in 23 (85 %) out of the 27 patients. Furthermore, the calculated sensitivity, specificity and diagnostic accuracy for the detection of nodal positive patients (n = 11) were 91 %, 94 % and 93 %, respectively. PET/MRI correctly identified regional metastatic disease (N1-stage) in 8/10 (80 %) patients and non-regional lymph node metastases in 5/5 (100 %) patients. In addition, quantitative analysis of PET and MRI derived functional parameters (SUV; ADC values) revealed a significant correlation with pathological grade and tumor size (p < 0.05). The present study demonstrates the high potential of integrated PET/MRI for the assessment of primary tumor and the detection of lymph node metastases in patients with cervical cancer. Providing additional prognostic information, PET/MRI may serve as a valuable diagnostic tool for cervical cancer patients in a pretreatment setting

  9. Total integrated slidable and valveless solid phase extraction-polymerase chain reaction-capillary electrophoresis microdevice for mini Y chromosome short tandem repeat genotyping.

    Science.gov (United States)

    Kim, Yong Tae; Lee, Dohwan; Heo, Hyun Young; Sim, Jeong Eun; Woo, Kwang Man; Kim, Do Hyun; Im, Sung Gap; Seo, Tae Seok

    2016-04-15

    A fully integrated slidable and valveless microsystem, which performs solid phase DNA extraction (SPE), micro-polymerase chain reaction (μPCR) and micro-capillary electrophoresis (μCE) coupled with a portable genetic analyser, has been developed for forensic genotyping. The use of a slidable chip, in which a 1 μL-volume of the PCR chamber was patterned at the center, does not necessitate any microvalves and tubing systems for fluidic control. The functional micro-units of SPE, μPCR, and μCE were fabricated on a single glass wafer by conventional photolithography, and the integrated microdevice consists of three layers: from top to bottom, a slidable chip, a channel wafer in which a SPE chamber, a mixing microchannel, and a CE microchannel were fabricated, and a Ti/Pt resistance temperature detector (RTD) wafer. The channel glass wafer and the RTD glass wafer were thermally bonded, and the slidable chip was placed on the designated functional unit. The entire process from the DNA extraction using whole human blood sample to identification of target Y chromosomal short tandem repeat (STR) loci was serially carried out with simply sliding the slidable chamber from one to another functional unit. Monoplex and multiplex detection of amelogenin and mini Y STR loci were successfully analysed on the integrated slidable SPE-μPCR-μCE microdevice by using 1 μL whole human blood within 60 min. The proposed advanced genetic analysis microsystem is capable of point-of-care DNA testing with sample-in-answer-out capability, more importantly, without use of complicated microvalves and microtubing systems for liquid transfer.

  10. Gum arabic-coated radioactive gold nanoparticles cause no short-term local or systemic toxicity in the clinically relevant canine model of prostate cancer

    Directory of Open Access Journals (Sweden)

    Axiak-Bechtel SM

    2014-10-01

    Full Text Available Sandra M Axiak-Bechtel,1 Anandhi Upendran,2,3 Jimmy C Lattimer,1 James Kelsey,3,4 Cathy S Cutler,4 Kim A Selting,1 Jeffrey N Bryan,1 Carolyn J Henry,1,5 Evan Boote,6 Deborah J Tate,1 Margaret E Bryan,7 Kattesh V Katti,3,8 Raghuraman Kannan3,8 1Department of Veterinary Medicine and Surgery, 2Department of Physics, University of Missouri, Columbia, MO, USA; 3Nanoparticle Biochem, Inc., and Shasun-NBI LLC, Columbia, MO, USA; 4Missouri University Research Reactor, 5Department of Internal Medicine, University of Missouri, Columbia, MO, USA; 6Spectrum Health, Grand Rapids, MI, USA; 7Department of Statistics, 8Department of Radiology, University of Missouri, Columbia, MO, USA Introduction: Gum arabic-coated radioactive gold nanoparticles (GA-198AuNPs offer ­several advantages over traditional brachytherapy in the treatment of prostate cancer, including homogenous dose distribution and higher dose-rate irradiation. Our objective was to determine the short-term safety profile of GA-198AuNPs injected intralesionally. We proposed that a single treatment of GA-198AuNPs would be safe with minimal-to-no evidence of systemic or local toxicity.Methods: Nine dogs with spontaneously occurring prostatic cancer were treated. Injections were performed with ultrasound or computerized tomography guidance. Complete blood counts, chemistry panels, and urinalyses were performed at weekly intervals for 1 month and imaging was repeated 4 weeks postinjection. Planar scintigraphic images were obtained within 30 minutes of injection.Results: No statistically significant difference was found in any hematologic or biochemical parameter studied, nor was any evidence of tumor swelling or abscessation found in eight dogs with repeat imaging; one dog died secondary to urethral obstruction 12 days following injection. At 30 minutes postinjection, an average of 53% of injected dose in seven dogs was retained in the prostate, with loss of remaining activity in the bladder and

  11. Integrated screening concept in women with genetic predisposition for breast cancer; Integriertes Frueherkennungskonzept bei Frauen mit genetischer Praedisposition fuer Brustkrebs

    Energy Technology Data Exchange (ETDEWEB)

    Bick, U. [Muenster Univ. (Germany). Inst. fuer Klinische Radiologie

    1997-08-01

    Breast cancer is in 5% of cases due to a genetic disposition. BRCA1 and BRCA2 are by far the most common breast cancer susceptibility genes. For a woman with a genetic predisposition, the individual risk of developing breast cancer sometime in her life is between 70 and 90%. Compared to the spontaneous forms of breast cancer, woman with a genetic predisposition often develop breast cancer at a much younger age. This is why conventional screening programs on the basis of mammography alone cannot be applied without modification to this high-risk group. In this article, an integrated screening concept for women with genetic prodisposition for breast cancer using breast self-examination, clinical examination, ultrasound, mammography and magnetic resonance imaging is introduced. (orig.) [Deutsch] Mammakarzinome sind in etwa 5% auf eine genetische Disposition zurueckzufuehren. Am haeufigsten finden sich Mutationen im Bereich der Gene BRCA1 und BRCA2. Frauen mit einer genetischen Disposition erkranken in etwa 70-90% im Laufe ihres Lebens an einem Mammakarzinom. Das Erkrankungsalter bei diesen Frauen liegt in der Regel deutlich niedriger als bei den spontanen Formen des Mammakarzinoms, so dass vorhandene Frueherkennungskonzepte auf der Basis eines Mammographiescrennings nicht ohne weiteres auf dieses Hochrisikokollektiv uebertragbar sind. Im folgenden wird ein integriertes Konzept zur Frueherkennung bei Frauen mit genetischer Praedisposition fuer ein Mammakarzinom auf der Basis von Brustselbstuntersuchung, klinischer Untersuchung, Sonographie, Mammographie und Magnetresonanztomographie vorgestellt. (orig.)

  12. Measurement equivalence of the Patient Reported Outcomes Measurement Information System® (PROMIS® Pain Interference short form items: Application to ethnically diverse cancer and palliative care populations

    Directory of Open Access Journals (Sweden)

    Jeanne A. Teresi

    2016-06-01

    Full Text Available Reducing the response burden of standardized pain measures is desirable, particularly for individuals who are frail or live with chronic illness, e.g., those suffering from cancer and those in palliative care. The Patient Reported Outcome Measurement Information System® (PROMIS® project addressed this issue with the provision of computerized adaptive tests (CAT and short form measures that can be used clinically and in research. Although there has been substantial evaluation of PROMIS item banks, little is known about the performance of PROMIS short forms, particularly in ethnically diverse groups. Reviewed in this article are findings related to the differential item functioning (DIF and reliability of the PROMIS pain interference short forms across diverse socio-demographic groups. Methods: DIF hypotheses were generated for the PROMIS short form pain interference items. Initial analyses tested item response theory (IRT model assumptions of unidimensionality and local independence. Dimensionality was evaluated using factor analytic methods; local dependence (LD was tested using IRT-based LD indices. Wald tests were used to examine group differences in IRT parameters, and to test DIF hypotheses. A second DIF-detection method used in sensitivity analyses was based on ordinal logistic regression with a latent IRT-derived conditioning variable. Magnitude and impact of DIF were investigated, and reliability and item and scale information statistics were estimated. Results: The reliability of the short form item set was excellent. However, there were a few items with high local dependency, which affected the estimation of the final discrimination parameters. As a result, the item, “How much did pain interfere with enjoyment of social activities?” was excluded in the DIF analyses for all subgroup comparisons. No items were hypothesized to show DIF for race and ethnicity; however, five items showed DIF after adjustment for multiple comparisons in

  13. Mesenteric ischemia after capecitabine treatment in rectal cancer and resultant short bowel syndrome is not an absolute contraindication for radical oncological treatment

    Directory of Open Access Journals (Sweden)

    Perpar Ana

    2015-06-01

    Full Text Available Background. Thrombotic events, arterial or venous in origin, still remain a source of substantial morbidity and mortality in cancer patients. The propensity for their development in oncology patients is partially a consequence of the disease itself and partially a result of our attempts to treat it. One of the rarest and deadliest thromboembolic complications is arterial mesenteric ischemia. The high mortality rate is caused by its rarity and by its non-specific clinical presentation, both of which make early diagnosis and treatment difficult. Hence, most diagnoses and treatments occur late in the course of the disease. The issue survivors of arterial mesenteric ischemia may face is short bowel syndrome, which has become a chronic condition after the introduction of parenteral nutrition at home.

  14. Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer.

    Science.gov (United States)

    Wu, Chunxiao; Wyatt, Alexander W; Lapuk, Anna V; McPherson, Andrew; McConeghy, Brian J; Bell, Robert H; Anderson, Shawn; Haegert, Anne; Brahmbhatt, Sonal; Shukin, Robert; Mo, Fan; Li, Estelle; Fazli, Ladan; Hurtado-Coll, Antonio; Jones, Edward C; Butterfield, Yaron S; Hach, Faraz; Hormozdiari, Fereydoun; Hajirasouliha, Iman; Boutros, Paul C; Bristow, Robert G; Jones, Steven Jm; Hirst, Martin; Marra, Marco A; Maher, Christopher A; Chinnaiyan, Arul M; Sahinalp, S Cenk; Gleave, Martin E; Volik, Stanislav V; Collins, Colin C

    2012-05-01

    Next-generation sequencing is making sequence-based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology-pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora. Despite a homogeneous cell type, our transcriptome analysis revealed signatures of both luminal and neuroendocrine cell types. Remarkably, the repertoire of expressed but apparently private gene fusions, including C15orf21:MYC, recapitulated this biology. We hypothesize that the amplification and over-expression of the stem cell gene MSI2 may have contributed to the stable hybrid cellular identity. This hybrid luminal-neuroendocrine tumour appears to represent a novel and highly aggressive case of prostate cancer with unique biological features and, conceivably, a propensity for rapid progression to castrate-resistance. Overall, this work highlights the importance of integrated analyses of genome, exome and transcriptome sequences for basic tumour biology, sequence-based molecular pathology and personalized oncology.

  15. Canadian Lung Cancer Relative Risk from Radon Exposure for Short Periods in Childhood Compared to a Lifetime

    Directory of Open Access Journals (Sweden)

    Jing Chen

    2013-05-01

    Full Text Available Long-term exposure to elevated indoor radon concentrations has been determined to be the second leading cause of lung cancer in adults after tobacco smoking. With the establishment of a National Radon Program in Canada in 2007 thousands of homes across the country have been tested for radon. Although the vast majority of people are exposed to low or moderate radon concentrations; from time to time; there are homes found with very high concentrations of radon. Among those living in homes with very high radon concentrations, it is typically parents of young children that demonstrate a great deal of concern. They want to know the equivalent risk in terms of the lifetime relative risk of developing lung cancer when a child has lived in a home with high radon for a few years. An answer to this question of risk equivalency is proposed in this paper. The results demonstrate clearly that the higher the radon concentration; the sooner remedial measures should be undertaken; as recommended by Health Canada in the Canadian radon guideline.

  16. Identifying Liver Cancer-Related Enhancer SNPs by Integrating GWAS and Histone Modification ChIP-seq Data

    Directory of Open Access Journals (Sweden)

    Tianjiao Zhang

    2016-01-01

    Full Text Available Many disease-related single nucleotide polymorphisms (SNPs have been inferred from genome-wide association studies (GWAS in recent years. Numerous studies have shown that some SNPs located in protein-coding regions are associated with numerous diseases by affecting gene expression. However, in noncoding regions, the mechanism of how SNPs contribute to disease susceptibility remains unclear. Enhancer elements are functional segments of DNA located in noncoding regions that play an important role in regulating gene expression. The SNPs located in enhancer elements may affect gene expression and lead to disease. We presented a method for identifying liver cancer-related enhancer SNPs through integrating GWAS and histone modification ChIP-seq data. We identified 22 liver cancer-related enhancer SNPs, 9 of which were regulatory SNPs involved in distal transcriptional regulation. The results highlight that these enhancer SNPs may play important roles in liver cancer.

  17. Identifying Liver Cancer-Related Enhancer SNPs by Integrating GWAS and Histone Modification ChIP-seq Data

    Science.gov (United States)

    Hu, Yang; Wu, Xiaoliang; Ma, Rui

    2016-01-01

    Many disease-related single nucleotide polymorphisms (SNPs) have been inferred from genome-wide association studies (GWAS) in recent years. Numerous studies have shown that some SNPs located in protein-coding regions are associated with numerous diseases by affecting gene expression. However, in noncoding regions, the mechanism of how SNPs contribute to disease susceptibility remains unclear. Enhancer elements are functional segments of DNA located in noncoding regions that play an important role in regulating gene expression. The SNPs located in enhancer elements may affect gene expression and lead to disease. We presented a method for identifying liver cancer-related enhancer SNPs through integrating GWAS and histone modification ChIP-seq data. We identified 22 liver cancer-related enhancer SNPs, 9 of which were regulatory SNPs involved in distal transcriptional regulation. The results highlight that these enhancer SNPs may play important roles in liver cancer. PMID:27429976

  18. The Adherence to Physical Exercise in a Group of Prostate Cancer: an Integrated Model to Improve the Quality of Life

    Directory of Open Access Journals (Sweden)

    Bernat-Carles Serdà i Ferrer

    2011-12-01

    Full Text Available This article presents the design and implementation of a model of adherence integrated into an exercise program in men with prostate cancer to get the autonomous practice at home. The study design is qualitative following Grounded Theory principles. The sample of 33 participants and it has been built through an intensive sampling by theoretical representativeness. The analytical procedure corresponds to the Method of Constants Comparisons. The design of simple and flexible program with a modular structure allows the user to adapt the exercise to his health, his symptoms resulting from the disease and his everyday life situation. The figure of professional trainer is essential in the process of achieving the autonomy. Working adherence as a process empowers the participant to maintain the autonomous activity at home. The adherence model integrated to a group exercise program is effective for improving the quality of life of older people affected by prostate cancer.

  19. SIGMA2: A system for the integrative genomic multi-dimensional analysis of cancer genomes, epigenomes, and transcriptomes

    Directory of Open Access Journals (Sweden)

    MacAulay Calum

    2008-10-01

    Full Text Available Abstract Background High throughput microarray technologies have afforded the investigation of genomes, epigenomes, and transcriptomes at unprecedented resolution. However, software packages to handle, analyze, and visualize data from these multiple 'omics disciplines have not been adequately developed. Results Here, we present SIGMA2, a system for the integrative genomic multi-dimensional analysis of cancer genomes, epigenomes, and transcriptomes. Multi-dimensional datasets can be simultaneously visualized and analyzed with respect to each dimension, allowing combinatorial integration of the different assays belonging to the different 'omics. Conclusion The identification of genes altered at multiple levels such as copy number, loss of heterozygosity (LOH, DNA methylation and the detection of consequential changes in gene expression can be concertedly performed, establishing SIGMA2 as a novel tool to facilitate the high throughput systems biology analysis of cancer.

  20. Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer

    OpenAIRE

    H Billur Engin; Emre Guney; Ozlem Keskin; Baldo Oliva; Attila Gursoy

    2013-01-01

    Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer H. Billur Engin1, Emre Guney2, Ozlem Keskin1, Baldo Oliva2, Attila Gursoy1* 1 Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Istanbul, Turkey, 2 Structural Bioinformatics Group (GRIB), Universitat Pompeu Fabra Abstract Blocking specific protein interactions can lead to human diseases. Accordingly, protein i...

  1. Effect of short message service as a reminder on breast self-examination in breast cancer patients: a randomized controlled trial.

    Science.gov (United States)

    Chung, Il Yong; Kang, Eunyoung; Yom, Cha Kyong; Kim, Dongwon; Sun, Young; Hwang, Yoonsun; Jang, Jin Youn; Kim, Sung-Won

    2015-04-01

    This study was a single-blind randomized controlled trial to assess the effectiveness of SMS as a reminder for breast self-examination (BSE). Participants who underwent surgery for breast cancer were recruited and randomized to the intervention group or the control group. Subjects in the intervention group received one text message on the first day of every month that reminded them to complete monthly BSE and the other text message on the fifteenth day of every month that contained information about breast cancer. Primary and secondary outcomes were self-reported BSE adherence and the frequency of BSE over 6 months. Between August 2010 and December 2011, 216 patients were randomly assigned to the SMS group (n = 110) or the control group (n = 106). A total of 202 patients were included in the final analysis. Self-reported BSE adherence and the frequency of BSE over the past six months were significantly higher in the intervention group than in the control group. Multivariate analysis showed that the SMS was the only significant factor for BSE adherence (p < 0.001). The short-term results of our study suggest that SMS is an effective and low-cost method to enhance adherence to BSE with existing information technology infrastructure.

  2. Microfluidic chip with integrated electrical cell-impedance sensing for monitoring single cancer cell migration in three-dimensional matrixes.

    Science.gov (United States)

    Nguyen, Tien Anh; Yin, Tsung-I; Reyes, Diego; Urban, Gerald A

    2013-11-19

    Cell migration has been recognized as one hallmark of malignant tumor progression. By integrating the method of electrical cell-substrate impedance sensing (ECIS) with the Boyden chamber design, the state-of-the-art techniques provide kinetic information about cell migration and invasion processes in three-dimensional (3D) extracellular matrixes. However, the information related to the initial stage of cell migration with single-cell resolution, which plays a unique role in the metastasis-invasion cascade of cancer, is not yet available. In this paper, we present a microfluidic device integrated with ECIS for investigating single cancer cell migration in 3D matrixes. Using microfluidics techniques without the requirement of physical connections to off-chip pneumatics, the proposed sensor chip can efficiently capture single cells on microelectrode arrays for sequential on-chip 2D or 3D cell culture and impedance measurement. An on-chip single-cell migration assay was successfully demonstrated within several minutes. Migration of single metastatic MDA-MB-231 cells in their initial stage can be monitored in real time; it shows a rapid change in impedance magnitude of approximately 10 Ω/s, whereas no prominent impedance change is observed for less-metastasis MCF-7 cells. The proposed sensor chip, allowing for a rapid and selective detection of the migratory properties of cancer cells at the single-cell level, could be applied as a new tool for cancer research.

  3. Short-term emergency response planning and risk assessment via an integrated modeling system for nuclear power plants in complex terrain

    Institute of Scientific and Technical Information of China (English)

    Ni-Bin CHANG; Yu-Chi WENG

    2013-01-01

    Short-term predictions of potential impacts from accidental release of various radionuclides at nuclear power plants are acutely needed,especially after the Fukushima accident in Japan.An integrated modeling system that provides expert services to assess the consequences of accidental or intentional releases of radioactive materials to the atmosphere has received wide attention.These scenarios can be initiated either by accident due to human,software,or mechanical failures,or from intentional acts such as sabotage and radiological dispersal devices.Stringent action might be required just minutes after the occurrence of accidental or intentional release.To fulfill the basic functions of emergency preparedness and response systems,previous studies seldom consider the suitability of air pollutant dispersion models or the connectivity between source term,dispersion,and exposure assessment models in a holistic context for decision support.Therefore,the Gaussian plume and puff models,which are only suitable for illustrating neutral air pollutants in flat terrain conditional to limited meteorological situations,are frequently used to predict the impact from accidental release of industrial sources.In situations with complex terrain or special meteorological conditions,the proposing emergency response actions might be questionable and even intractable to decisionmakers responsible for maintaining public health and environmental quality.This study is a preliminary effort to integrate the source term,dispersion,and exposure assessment models into a Spatial Decision Support System (SDSS) to tackle the complex issues for short-term emergency response planning and risk assessment at nuclear power plants.Through a series model screening procedures,we found that the diagnostic (objective) wind field model with the aid of sufficient on-site meteorological monitoring data was the most applicable model to promptly address the trend of local wind field patterns.However,most of the

  4. Short-term emergency response planning and risk assessment via an integrated modeling system for nuclear power plants in complex terrain

    Science.gov (United States)

    Chang, Ni-Bin; Weng, Yu-Chi

    2013-03-01

    Short-term predictions of potential impacts from accidental release of various radionuclides at nuclear power plants are acutely needed, especially after the Fukushima accident in Japan. An integrated modeling system that provides expert services to assess the consequences of accidental or intentional releases of radioactive materials to the atmosphere has received wide attention. These scenarios can be initiated either by accident due to human, software, or mechanical failures, or from intentional acts such as sabotage and radiological dispersal devices. Stringent action might be required just minutes after the occurrence of accidental or intentional release. To fulfill the basic functions of emergency preparedness and response systems, previous studies seldom consider the suitability of air pollutant dispersion models or the connectivity between source term, dispersion, and exposure assessment models in a holistic context for decision support. Therefore, the Gaussian plume and puff models, which are only suitable for illustrating neutral air pollutants in flat terrain conditional to limited meteorological situations, are frequently used to predict the impact from accidental release of industrial sources. In situations with complex terrain or special meteorological conditions, the proposing emergency response actions might be questionable and even intractable to decisionmakers responsible for maintaining public health and environmental quality. This study is a preliminary effort to integrate the source term, dispersion, and exposure assessment models into a Spatial Decision Support System (SDSS) to tackle the complex issues for short-term emergency response planning and risk assessment at nuclear power plants. Through a series model screening procedures, we found that the diagnostic (objective) wind field model with the aid of sufficient on-site meteorological monitoring data was the most applicable model to promptly address the trend of local wind field patterns

  5. Effects of massive wind power integration on short-term water resource management in central Chile - a grid-wide study

    Science.gov (United States)

    Haas, J.; Olivares, M. A.; Palma, R.

    2013-12-01

    In central Chile, water from reservoirs and streams is mainly used for irrigation and power generation. Hydropower reservoirs operation is particularly challenging because: i) decisions at each plant impact the entire power system, and ii) the existence of large storage capacity implies inter-temporal ties. An Independent System Operator (ISO) decides the grid-wide optimal allocation of water for power generation, under irrigation-related constraints. To account for the long-term opportunity cost of water, a future cost function is determined and used in the short term planning. As population growth and green policies demand increasing levels of renewable energy in power systems, deployment of wind farms and solar plants is rising quickly. However, their power output is highly fluctuating on short time scales, affecting the operation of power plants, particularly those fast responding units as hydropower reservoirs. This study addresses these indirect consequences of massive introduction of green energy sources on reservoir operations. Short-term reservoir operation, under different wind penetration scenarios, is simulated using a replica of Chile's ISO's scheduling optimization tools. Furthermore, an ongoing study is exploring the potential to augment the capacity the existing hydro-power plants to better cope with the balancing needs due to a higher wind power share in the system. As reservoir releases determine to a great extent flows at downstream locations, hourly time series of turbined flows for 24-hour periods were computed for selected combinations between new wind farms and increased capacity of existing hydropower plants. These time series are compiled into subdaily hydrologic alteration (SDHA) indexes (Zimmerman et al, 2010). The resulting sample of indexes is then analyzed using duration curves. Results show a clear increase in the SDHA for every reservoir of the system as more fluctuating renewables are integrated into the system. High

  6. C-erbB-2 onco-protein expression in breast cancer: relationship to tumour characteristics and short-term survival in Universiti Kebansaan Malaysia Medical Centre.

    Science.gov (United States)

    Sharifah, N A; Lee, B R; Clarence-Ko, C H; Tan, G C; Shiran, M S; Naqiyah, I; Rohaizak, M; Fuad, I; Tamil, A M

    2008-01-01

    Breast cancer is the commonest cancer affecting females in Malaysia, contributing 31% of all newly diagnosed cases amongst Malaysian women. The present retrospective cohort study evaluated the relationship between cerbB- 2 onco-protein overexpression with various tumour characteristics and survival rate of breast cancer patients treated at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between 1996-2000. CerbB- 2 oncoprotein overexpression was determined by immunohistochemistry (IHC) and tumors showing 2+ positivity were verified by Fluorescence In Situ Hybridization (FISH). One hundred and seventy two patients were eligible for the study with a short-term follow-up (median) of 5.1 years. C-erbB-2 oncoprotein overexpression correlated with lymph node positivity, oestrogen receptor (ER) and progesterone receptor (PR) negativity. Univariate analyses showed shorter disease free survival (DFS) and overall survival (OS) in patients with cerbB- 2 oncoprotein overexpression, Malay ethnicity, higher tumour grade, lymph node positivity, ER and PR negativity. In a subgroup of patients with c-erbB-2 oncoprotein overexpression, a shorter OS was observed in those with lymph node positivity, ER and PR negativity. In multivariate prognostic analysis, lymph node status, ER status and tumour grading were the strongest independent prognostic factors for both OS and DFS. However, c-erbB-2 status was not a significantly independent prognostic factor, even in subsets with lymph node positive or negative group. C-erbB-2 oncoprotein overexpression correlated well with lymph node status, ER and PR. Shorter OS and DFS were significantly observed in patients with c-erbB-2 oncoprotein overexpression. Lymph node status, ER status and tumour grading were the only three independent prognostic factors for OS and DFS in this study. Although c-erbB-2 expression is obviously important from a biological standpoint, multivariate analysis showed that it is not an independent prognostic

  7. An integrated approach to the prediction of chemotherapeutic response in patients with breast cancer.

    Directory of Open Access Journals (Sweden)

    Kelly H Salter

    Full Text Available A major challenge in oncology is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in cancer patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent and limiting the agents used to those most likely to be effective.Using gene expression data on the NCI-60 and corresponding drug sensitivity, mRNA and microRNA profiles were developed representing sensitivity to individual chemotherapeutic agents. The mRNA signatures were tested in an independent cohort of 133 breast cancer patients treated with the TFAC (paclitaxel, 5-fluorouracil, adriamycin, and cyclophosphamide chemotherapy regimen. To further dissect the biology of resistance, we applied signatures of oncogenic pathway activation and performed hierarchical clustering. We then used mRNA signatures of chemotherapy sensitivity to identify alternative therapeutics for patients resistant to TFAC. Profiles from mRNA and microRNA expression data represent distinct biologic mechanisms of resistance to common cytotoxic agents. The individual mRNA signatures were validated in an independent dataset of breast tumors (P = 0.002, NPV = 82%. When the accuracy of the signatures was analyzed based on molecular variables, the predictive ability was found to be greater in basal-like than non basal-like patients (P = 0.03 and P = 0.06. Samples from patients with co-activated Myc and E2F represented the cohort with the lowest percentage (8% of responders. Using mRNA signatures of sensitivity to other cytotoxic agents, we predict that TFAC non-responders are more likely to be sensitive to docetaxel (P = 0.04, representing a viable alternative therapy.Our results suggest that the optimal strategy for chemotherapy sensitivity prediction integrates molecular variables such as ER and HER2 status with corresponding micro

  8. Short-Course Treatment With Gefitinib Enhances Curative Potential of Radiation Therapy in a Mouse Model of Human Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bokobza, Sivan M.; Jiang, Yanyan; Weber, Anika M.; Devery, Aoife M.; Ryan, Anderson J., E-mail: anderson.ryan@oncology.ox.ac.uk

    2014-03-15

    Purpose: To evaluate the combination of radiation and an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in preclinical models of human non-small cell lung cancer. Methods and Materials: Sensitivity to an EGFR TKI (gefitinib) or radiation was assessed using proliferation assays and clonogenic survival assays. Effects on receptor signal transduction pathways (pEGFR, pAKT, pMAPK) and apoptosis (percentage of cleaved PARP Poly (ADP-ribose) polymerase (PARP)) were assessed by Western blotting. Radiation-induced DNA damage was assessed by γH2AX immunofluorescence. Established (≥100 mm{sup 3}) EGFR-mutated (HCC287) or EGFR wild-type (A549) subcutaneous xenografts were treated with radiation (10 Gy, day 1) or gefitinib (50 mg/kg, orally, on days 1-3) or both. Results: In non-small cell lung cancer (NSCLC) cell lines with activating EGFR mutations (PC9 or HCC827), gefitinib treatment markedly reduced pEGFR, pAKT, and pMAPK levels and was associated with an increase in cleaved PARP but not in γH2AX foci. Radiation treatment increased the mean number of γH2AX foci per cell but did not significantly affect EGFR signaling. In contrast, NSCLC cell lines with EGFR T790M (H1975) or wild-type EGFR (A549) were insensitive to gefitinib treatment. The combination of gefitinib and radiation treatment in cell culture produced additive cell killing with no evidence of synergy. In xenograft models, a short course of gefitinib (3 days) did not significantly increase the activity of radiation treatment in wild-type EGFR (A549) tumors (P=.27), whereas this combination markedly increased the activity of radiation (P<.001) or gefitinib alone (P=.002) in EGFR-mutated HCC827 tumors, producing sustained tumor regressions. Conclusions: Gefitinib treatment increases clonogenic cell killing by radiation but only in cell lines sensitive to gefitinib alone. Our data suggest additive rather than synergistic interactions between gefitinib and radiation and that a

  9. Therapeutic Evaluation on Advanced Pancreatic Cancer Treated by Integrative Chinese and Western Medicine Clinical Analysis of 56 Cases

    Institute of Scientific and Technical Information of China (English)

    刘鲁明; 吴良村; 林胜友; 杨维鸿; 郭勇; 徐颖扉; 舒琦瑾

    2003-01-01

    Objective: In comparison with chemotherapy, to evaluate therapeutic effcts on advanced pancreatic cancer treated by integrative Chinese and western medicine (ICWM) therapies. Methods: Based on the retrospective study of 56 patients with advanced pancreatic cancer,life table was applied to the analysis of patients' survival rate and χ2 test to the comparison of therapeutic response between ICWM and chemotherapy groups. Results: The results showed that 1-year survival rate in the ICWM group was 55.37%±3.24%; 2-year survival rate 34.61%±16.31%; 3-year survival rate 25.96%±24.64%; 5-year survival rate 25.96%±24.64%; and median survival period 16.3 months. However 1-year survival rate in the chemotherapy group was 21.95%±27.54%; 2-year survival rate 7.31%±27.54%; 3-year survival rate 0%; and median survival period 7.5 months. The therapeutic effects between two groups were significantly different (P=0.004). Further analysis suggested that the reduction of cancer mass in the ICWM group was more than that in chemotherapy group (P=0.049) and the improvement of advanced pancreatic cancer related-symptoms better than that of chemotherapy group (P=0.002). Conclusion: The ICWM comprehensive therapy is of important value in the treatment of advanced pancreatic cancer.

  10. The road map towards providing a robust Raman spectroscopy-based cancer diagnostic platform and integration into clinic

    Science.gov (United States)

    Lau, Katherine; Isabelle, Martin; Lloyd, Gavin R.; Old, Oliver; Shepherd, Neil; Bell, Ian M.; Dorney, Jennifer; Lewis, Aaran; Gaifulina, Riana; Rodriguez-Justo, Manuel; Kendall, Catherine; Stone, Nicolas; Thomas, Geraint; Reece, David

    2016-03-01

    Despite the demonstrated potential as an accurate cancer diagnostic tool, Raman spectroscopy (RS) is yet to be adopted by the clinic for histopathology reviews. The Stratified Medicine through Advanced Raman Technologies (SMART) consortium has begun to address some of the hurdles in its adoption for cancer diagnosis. These hurdles include awareness and acceptance of the technology, practicality of integration into the histopathology workflow, data reproducibility and availability of transferrable models. We have formed a consortium, in joint efforts, to develop optimised protocols for tissue sample preparation, data collection and analysis. These protocols will be supported by provision of suitable hardware and software tools to allow statistically sound classification models to be built and transferred for use on different systems. In addition, we are building a validated gastrointestinal (GI) cancers model, which can be trialled as part of the histopathology workflow at hospitals, and a classification tool. At the end of the project, we aim to deliver a robust Raman based diagnostic platform to enable clinical researchers to stage cancer, define tumour margin, build cancer diagnostic models and discover novel disease bio markers.

  11. Therapeutic Evaluation on Advanced Pancreatic Cancer Treated by Integrative Chinese and Western Medicine—Clinical Analysis of 56 Cases

    Institute of Scientific and Technical Information of China (English)

    LIULu-ming; WULiang-cun; 等

    2003-01-01

    Objective:In comparison with chemotherapy,to evaluate therapeutic effects on advanced pancreatic cancer treated by integrative Chinese and western medicine(ICWM) therapies.Methods:Based on the retrospective study of 56 patients with advanced pancreatic cancer,life table was applied to the anal-ysis of patients' survival rate and X2 test to the comparison of therapeutic response between ICWM and chemotherapy groups.Results:The results showed that 1-year survival rate 25.96%±24.64%; 5-year 37%±3.24%;2-year survival rate 34.61%±16.31%;3-year survival rate 25.96%±24.64%;5-year survival rate 25.96%±24.64%; and median survival period 16.3 months.However 1-year survival rate in the chemotherapy group was 21.95%±27.54%;2-year survival rate 7.31%±27.54%;3-year survival rate 0%; and median survival period 7.5months.The therapeutic effects between two groups were signifi-cantly different(P=0.004).Further analysis suggested that the reduction of cancer mass in the ICWM group was more than that in chemotherapy group(P=0.049) and the improvement of advanced pancreatic cancer related-symptoms better than that of chemotherapy group(P=0.002).Conclusion:The ICWM comprehensive therapy is of important value in the treatment of advanced pancreatic cancer.

  12. Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Callinice D. Capo-chichi; Kathy Q. Car; Jennifer Smedberg; Parvin Ganjei-Azar; Andrew K. Godwin; Xiang-Xi Xu

    2011-01-01

    Through advances in technology, the genetic basis of cancer has been investigated at the genomic level, and many fundamental questions have begun to be addressed. Among several key unresolved questions in cancer biology, the molecular basis for the link between nuclear deformation and malignancy has not been determined. Another hallmark of human cancer is aneuploidy; however, the causes and consequences of aneuploidy are unanswered and are hotly contested topics. We found that nuclear lamina proteins lamin A/C are absent in a significant fraction (38%) of human breast cancer tissues. Even in lamin A/C-positive breast cancer, lamin A/C expression is heterogeneous or aberrant (such as nonnuclear distribution) in the population of tumor cells, as determined by immunohistology and immunofluorescence microscopy. In most breast cancer cell lines, a significant fraction of the lamin A/Cnegative population was observed. To determine the consequences of the loss of lamin A/C, we suppressed their expression by shRNA in non-cancerous primary breast epithelial cells. Down-regulation of lamin A/C in breast epithelial cells led to morphological deformation, resembling that of cancer cells, as observed by immunofluorescence microscopy. The lamin A/C-suppressed breast epithelial cells developed aneuploidy as determined by both flow cytometry and fluorescence in situ hybridization. We conclude that the loss of nuclear envelope structural proteins lamin A/C in breast cancer underlies the two hallmarks of cancer aberrations in nuclear morphology and aneuploidy.

  13. Short Communication: Viral Suppression Is Associated with Increased Likelihood of Colorectal Cancer Screening Among Persons Living with HIV/AIDS.

    Science.gov (United States)

    Burkholder, Greer A; Tamhane, Ashutosh R; Appell, Lauren E; Willig, James H; Saag, Michael S; Raper, James L; Westfall, Andrew O; Mugavero, Michael J

    2015-05-01

    With improved survival and aging, more persons living with HIV/AIDS (PLWHA) are at risk for colorectal cancer (CRC). This retrospective longitudinal study evaluated patient characteristics associated with CRC screening in our HIV cohort. Patients were followed beginning at age 50 years during a study period from January 1, 2003 to December 31, 2010 (n=265). During a median follow-up time of 1.7 years, only 30% of patients underwent CRC screening. The majority of screened patients received endoscopic screening (colonoscopy, 86%; sigmoidoscopy, 8%); among these patients, results were available for 68/75, and adenomatous polyps were found in 13%. No cases of CRC were reported. Among unscreened patients, only 23% had an external primary care provider, indicating an HIV provider was the expected source for CRC screening referral in the majority. Patients with time-varying suppressed HIV viral load were more likely to receive screening (HRadjusted=1.74; 95% CI: 1.05-2.87), independent of CD4 count. Our findings suggest HIV providers are more likely to address non-HIV-related healthcare maintenance when HIV is controlled. In addition, a significant number of neoplastic lesions are likely being missed in PLWHA who have not been screened for CRC. Provision of evidence-based preventive care in addition to HIV care is required for the aging population of PLWHA.

  14. Impact of Short-term 1,25-Dihydroxyvitamin D3 on the Chemopreventive Efficacy of Erlotinib against Oral Cancer.

    Science.gov (United States)

    Bothwell, Katelyn D; Shaurova, Tatiana; Merzianu, Mihai; Suresh, Amritha; Kuriakose, Moni A; Johnson, Candace S; Hershberger, Pamela A; Seshadri, Mukund

    2015-09-01

    Activation of the epidermal growth factor receptor (EGFR) pathway is an early event in head and neck carcinogenesis. As a result, targeting EGFR for chemoprevention of head and neck squamous cell carcinomas (HNSCC) has received considerable attention. In the present study, we examined the impact of 1,25(OH)2D3, the active metabolite of the nutritional supplement vitamin D on the chemopreventive efficacy of the EGFR inhibitor, erlotinib, against HNSCC. Experimental studies were conducted in patient-derived xenografts (PDX) and the 4-nitroquinoline-1-oxide (4NQO) carcinogen-induced model of HNSCC. Short-term treatment (4 weeks) of PDX-bearing mice with 1,25(OH)2D3 and erlotinib resulted in significant inhibition of tumor growth. Noninvasive MRI enabled longitudinal monitoring of disease progression in the 4NQO model with 100% of control animals showing evidence of neoplastic lesions by 24 weeks. Among the experimental groups, animals treated with the combination regimen showed the greatest reduction in tumor incidence and volume (P phospho-EGFR and phospho-Akt with the combination regimen. These results highlight the potential of 1,25(OH)2D3 to augment the efficacy of erlotinib against HNSCC. Further optimization of schedule and sequence of this combination regimen along with investigation into the activity of less calcemic analogues or dietary vitamin D is essential to fully realize the potential of this approach.

  15. Integration of Anatomic and Pathogenetic Bases for Early Lung Cancer Diagnosis

    Science.gov (United States)

    2007-03-01

    cell lung cancer and their correlation to clinical parameters and survival. BMC Cancer (BMC cancer [ electronic resource].) 2004; 4(1): 66. [44...steps: printing and immobilization of capture antibodies on a functionalized surface (usually glass slide covered with poly-L-lysine, aldehyde , epoxy or...associated with cigarette smoking. Int J Epidemil, 1993. 22(4): p.592-9. [46] Pope M, Ashley MJ, Ferrence R. The carcinogenic and toxic effects of tobacco

  16. Microfluidics and cancer analysis: cell separation, cell/tissue culture, cell mechanics, and integrated analysis systems.

    Science.gov (United States)

    Pappas, Dimitri

    2016-01-21

    Among the growing number of tools available for cancer studies, microfluidic systems have emerged as a promising analytical tool to elucidate cancer cell and tumor function. Microfluidic methods to culture cells have created approaches to provide a range of environments from single-cell analysis to complex three-dimensional devices. In this review we discuss recent advances in tumor cell culture, cancer cell analysis, and advanced studies enabled by microfluidic systems.

  17. Simultaneous mapping of human papillomavirus integration sites and molecular karyotyping in short-term cultures of cervical carcinomas by using 49-color combined binary ratio labeling fluorescence in situ hybridization

    NARCIS (Netherlands)

    Brink, AATP; Wiegant, JCAG; Szuhai, K; Tanke, HJ; Kenter, GG; Fleuren, GJ; Schuuring, E; Raap, AK

    2002-01-01

    Infection with high-risk type human papillomavirus (HPV) is a necessary causal factor in the pathogenesis of cervical carcinoma. In most invasive cervical cancers, HPV is integrated in the host cell genome, and additional genetic aberrations are observed among which are chromosomal aberrations. To a

  18. Knowledge Toward Cancer Pain and the Use of Opioid Analgesics Among Medical Students in their Integrated Clinical Clerkship

    Directory of Open Access Journals (Sweden)

    Maria Fidelis C. Manalo

    2008-01-01

    Full Text Available Introduction: Among the focal issues of barriers to pain management include the physicians’ lack of knowledge about cancer pain and negative attitudes towards opioids. Many physicians and educators attribute this, at least in part, to limited exposure to pain and palliative care education during medical school.Aim: The researcher investigated the medical students’ knowledge about cancer pain and the use of opioid analgesics.Methods: The subjects were a sample of 50 students of the University of the Philippines College of Medicine in their integrated clinical clerkship year. Descriptive statistics (frequencies, means, standard deviation, rating scales were used to determine mean knowledge score and level of confidence with opioid use. The study also identified specific areas where students exhibited good or poor knowledge of opioids.Results: Approximately sixty-nine (69% of the study respondents mentioned that pain management was given to them during their Anesthesiology lectures while a few recalled that they had these lectures during their Family Medicine rotation in Supportive, Palliative and Hospice Care. More than a third (35% of the respondents admitted to not being confident with morphine use at present. The top three reasons cited as limitations in choice of opioids for cancer pain include fear of addiction, lack of adequate knowledge and experience and fear of side effects and complications. Out of a maximum of 13 correct answers, the mean knowledge score of the medical students was 6.6 ± 2.9. Less than 16% of the respondents had adequate knowledge on cancer pain and opioid use.Conclusions: The results show that basic knowledge of the role of opioids in cancer pain management among medical students in their integrated clinical clerkship year at the University of the Philippines is poor. The findings imply a need to look into making revisions in the medical curriculum to include a training program that will enable all students to

  19. Integrated Cellular and Plasma Proteomics of Contrasting B-cell Cancers Reveals Common, Unique and Systemic Signatures.

    Science.gov (United States)

    Johnston, Harvey E; Carter, Matthew J; Cox, Kerry L; Dunscombe, Melanie; Manousopoulou, Antigoni; Townsend, Paul A; Garbis, Spiros D; Cragg, Mark S

    2017-03-01

    Approximately 800,000 leukemia and lymphoma cases are diagnosed worldwide each year. Burkitt's lymphoma (BL) and chronic lymphocytic leukemia (CLL) are examples of contrasting B-cell cancers; BL is a highly aggressive lymphoid tumor, frequently affecting children, whereas CLL typically presents as an indolent, slow-progressing leukemia affecting the elderly. The B-cell-specific overexpression of the myc and TCL1 oncogenes in mice induce spontaneous malignancies modeling BL and CLL, respectively. Quantitative mass spectrometry proteomics and isobaric labeling were employed to examine the biology underpinning contrasting Eμ-myc and Eμ-TCL1 B-cell tumors. Additionally, the plasma proteome was evaluated using subproteome enrichment to interrogate biomarker emergence and the systemic effects of tumor burden. Over 10,000 proteins were identified (qIL5) receptor. IL5 treatment promoted Eμ-TCL1 tumor proliferation, suggesting an amplification of IL5-induced AKT signaling by TCL1. Tumor plasma contained a substantial tumor lysis signature, most prominent in Eμ-myc plasma, whereas Eμ-TCL1 plasma contained signatures of immune-response, inflammation and microenvironment interactions, with putative biomarkers in early-stage cancer. These findings provide a detailed characterization of contrasting B-cell tumor models, identifying common and specific tumor mechanisms. Integrated plasma proteomics allowed the dissection of a systemic response and a tumor lysis signature present in early- and late-stage cancers, respectively. Overall, this study suggests common B-cell cancer signatures exist and illustrates the potential of the further evaluation of B-cell cancer subtypes by integrative proteomics.

  20. Magnitude of fatigue in cancer patients receiving radiotherapy and its short term effect on quality of life

    Directory of Open Access Journals (Sweden)

    Janaki M

    2010-01-01

    Full Text Available Background : Fatigue is one of the most common, ongoing symptoms reported by patients undergoing radiotherapy and has profound effects on the quality of life. Aims : This study attempts to identify the magnitude of fatigue and its implication on the quality of life during radiotherapy. Methods and Materials : A prospective study was conducted from March 2004 to September 2005, on 90 patients with histologically proven cancer, receiving radiotherapy. Pretreatment and weekly assessment of fatigue and QOL was done during radiation treatment using Brief Fatigue Inventory Scale and EORTC QLQ C30 respectively and repeated one month after completion of radiotherapy. All the scores were measured in the 0 to 100 scale. Statistical Methods Used : Trimean, SPSS 11.0 and Sysstat 8.0 were used for statistical analysis. Results : Fatigue was present in 87.8% of patients initially and increased gradually over the course of radiotherapy and peaked in the last week. However at follow up it was nearing the pretreatment level. There was significant reduction in the functional scores ( P < 0.001 of QOL (physical, role and emotional function, which returned to pretreatment level at follow up. In the seventh week impairment of cognitive function (P=0.059 was noted. Significant reduction of social function (P < 0.001 at second week and global health status (P < 0.001 at fifth week was noted while financial difficulty was seen from second week onwards. Conclusion : Fatigue is transiently increased by radiotherapy before reaching pretreatment level after few weeks of completion of radiotherapy. QOL is also affected by fatigue which follows the same pattern.

  1. Short-term resveratrol exposure causes in vitro and in vivo growth inhibition and apoptosis of bladder cancer cells.

    Directory of Open Access Journals (Sweden)

    Mo-Li Wu

    Full Text Available Conventional adjuvant chemotherapies for bladder transitional cell carcinomas (TCCs may cause strong systemic toxicity and local irritation. Non-toxic resveratrol inhibits TCC cell growth but its feasibility in clinical management of TCCs remains obscure. This study aimed to evaluate the safety and anti-TCC efficacy of resveratrol, using the experimental models closer to the clinical treatment condition. Human TCC EJ cells were exposed to 100 µM, 150 µM and 200 µM resveratrol respectively for 1 hour and 2 hours to mimic intravesical drug instillation and the cell responses were analyzed by multiple experimental approaches. An orthotopic TCC nude mouse model was established by injecting EJ cells into the sub-urothelial layer and used for short-term intravesical resveratrol instillation. The safety of resveratrol instillation was evaluated and compared with that of MCC. The results revealed that 2 h 150 µM or 200 µM resveratrol treatment leaded to remarkable S phase arrest and apoptosis at 72 h time-point, accompanied with attenuated phosphorylation, nuclear translocation and transcription of STAT3, down-regulation of STAT3 downstream genes (survivin, cyclinD1, c-Myc and VEGF and nuclear translocations of Sirt1 and p53. The importance of STAT3 signaling in cell growth was confirmed by treating EJ cells with JAK2 inhibitor tyrphostin AG490. The efficacy and safety of resveratrol instillation were proved by the findings from nude mouse orthotopic xenograft models, because this treatment caused growth suppression, distinctive apoptosis and STAT3 inactivation of the transplanted tumors without affecting normal urothelium. Our results thus suggest for the first time the practical values of resveratrol as a safe and effective agent in the post-operative treatment of TCCs.

  2. Psycho-Spiritual Integrative Therapy: Psychological Intervention for Women with Breast Cancer

    Science.gov (United States)

    Corwin, Diana; Wall, Kathleen; Koopman, Cheryl

    2012-01-01

    Women with breast cancer frequently report psychological distress throughout the treatment process. Patients have several empirically supported options for group psychotherapy while undergoing breast cancer treatment. However, few interventions have been developed that incorporate spirituality into psychotherapy, despite indications that patients…

  3. Quality improvement by implementing an integrated oncological care pathway for breast cancer patients

    NARCIS (Netherlands)

    van Hoeve, J.; de Munck, L.; Otter, Renee; de Vries, J.; Siesling, S.

    2014-01-01

    Background and aim: In cancer care, more and more systemized approaches such as care pathways are used to reduce variation, reduce waiting- and throughput times and to improve quality of care. The aim of this study was to determine whether the implementation of a multidisciplinary breast cancer path

  4. Quality improvement by implementing an integrated oncological care pathway for breast cancer patients

    NARCIS (Netherlands)

    Hoeve, van J.; Munck, de L.; Otter, R.; Vries, de J.; Siesling, S.

    2014-01-01

    Background and aim In cancer care, more and more systemized approaches such as care pathways are used to reduce variation, reduce waiting- and throughput times and to improve quality of care. The aim of this study was to determine whether the implementation of a multidisciplinary breast cancer pathw

  5. Integrated analysis of the miRNA, gene and pathway regulatory network in gastric cancer.

    Science.gov (United States)

    Zhang, Haiyang; Qu, Yanjun; Duan, Jingjing; Deng, Ting; Liu, Rui; Zhang, Le; Bai, Ming; Li, Jialu; Zhou, Likun; Ning, Tao; Li, Hongli; Ge, Shaohua; Li, Hua; Ying, Guoguang; Huang, Dingzhi; Ba, Yi

    2016-02-01

    Gastric cancer is one of the most common malignant tumors worldwide; however, the efficacy of clinical treatment is limited. MicroRNAs (miRNAs) are a class of small non-coding RNAs that have been reported to play a key role in the development of cancer. They also provide novel candidates for targeted therapy. To date, in-depth studies on the molecular mechanisms of gastric cancer involving miRNAs are still absent. We previously reported that 5 miRNAs were identified as being significantly increased in gastric cancer, and the role of these miRNAs was investigated in the present study. By using bioinformatics tools, we found that more than 4,000 unique genes are potential downstream targets of gastric cancer miRNAs, and these targets belong to the protein class of nucleic acid binding, transcription factor, enzyme modulator, transferase and receptor. Pathway mapping showed that the targets of gastric cancer miRNAs are involved in the MAPK signaling pathway, pathways in cancer, the PI3K-Akt signaling pathway, the HTLV-1 signaling pathway and Ras signaling pathway, thus regulating cell growth, differentiation, apoptosis and metastasis. Analysis of the pathways related to miRNAs may provides potential drug targets for future therapy of gastric cancer.

  6. An MMP-2 Responsive Liposome Integrating Antifibrosis and Chemotherapeutic Drugs for Enhanced Drug Perfusion and Efficacy in Pancreatic Cancer.

    Science.gov (United States)

    Ji, Tianjiao; Li, Suping; Zhang, Yinlong; Lang, Jiayan; Ding, Yanping; Zhao, Xiao; Zhao, Ruifang; Li, Yiye; Shi, Jian; Hao, Jihui; Zhao, Ying; Nie, Guangjun

    2016-02-10

    Fibrotic stroma, a critical character of pancreatic tumor microenvironment, provides a critical barrier against the penetration and efficacy of various antitumor drugs. Therefore, new strategies are urgently needed to alleviate the fibrotic mass and increase the drug perfusion within pancreatic cancer tissue. In our current work, we developed a β-cyclodextrin (β-CD) modified matrix metalloproteinase-2 (MMP-2) responsive liposome, integrating antifibrosis and chemotherapeutic drugs for regulation of pancreatic stellate cells (PSCs), a key source of the fibrosis, and targeted delivery of cytotoxic drugs for pancreatic cancer therapy. These liposomes disassembed into two functional parts upon MMP-2 cleavage at the tumor site. One part was constituted by the β-CDs and the antifibrosis drug pirfenidone, which was kept in the stroma and inhibited the expression of collagen I and TGF-β in PSCs, down-regulating the fibrosis and decreasing the stromal barrier. The other segment, the RGD peptide-modified-liposome loading the chemotherapeutic drug gemcitabine, targeted and killed pancreatic tumor cells. This integrated nanomedicine, showing an increased drug perfusion without any overt side effects, may provide a potential strategy for improvement of the pancreatic cancer therapy.

  7. Short fiber reinforced thermoplastic blends

    NARCIS (Netherlands)

    Malchev, P.G.

    2008-01-01

    The present thesis investigates the potential of short fiber reinforced thermoplastic blends, a combination of an immiscible polymer blend and a short fiber reinforced composite, to integrate the easy processing solutions available for short fiber reinforced composites with the high mechanical perfo

  8. Detection of driver protein complexes in breast cancer metastasis by large-scale transcriptome-interactome integration.

    Science.gov (United States)

    Garcia, Maxime; Finetti, Pascal; Bertucci, Francois; Birnbaum, Daniel; Bidaut, Ghislain

    2014-01-01

    With the development of high-throughput gene expression profiling technologies came the opportunity to define genomic signatures predicting clinical condition or cancer patient outcome. However, such signatures show dependency on training set, lack of generalization, and instability, partly due to microarray data topology. Additional issues for analyzing tumor gene expression are that subtle molecular perturbations in driver genes leading to cancer and metastasis (masked in typical differential expression analysis) may provoke expression changes of greater amplitude in downstream genes (easily detected). In this chapter, we are describing an interactome-based algorithm, Interactome-Transcriptome Integration (ITI) that is used to find a generalizable signature for prediction of breast cancer relapse by superimposition of a large-scale protein-protein interaction data (human interactome) over several gene expression datasets. ITI extracts regions in the interactome whose expression is discriminating for predicting relapse-free survival in cancer and allow detection of subnetworks that constitutes a generalizable and stable genomic signature. In this chapter, we describe the practical aspects of running the full ITI pipeline (subnetwork detection and classification) on six microarray datasets.

  9. Integrating spot short-term measurements of carbon emissions and backward dietary energy partition calculations to estimate intake in lactating dairy cows fed ad libitum or restricted.

    Science.gov (United States)

    Pereira, A B D; Utsumi, S A; Dorich, C D; Brito, A F

    2015-12-01

    The objective of this study was to use spot short-term measurements of CH4 (QCH4) and CO2 (QCO2) integrated with backward dietary energy partition calculations to estimate dry matter intake (DMI) in lactating dairy cows. Twelve multiparous cows averaging 173±37d in milk and 4 primiparous cows averaging 179±27d in milk were blocked by days in milk, parity, and DMI (as a percentage of body weight) and, within each block, randomly assigned to 1 of 2 treatments: ad libitum intake (AL) or restricted intake (RI=90% DMI) according to a crossover design. Each experimental period lasted 22d with 14d for treatments adaptation and 8d for data and sample collection. Diets contained (dry matter basis): 40% corn silage, 12% grass-legume haylage, and 48% concentrate. Spot short-term gas measurements were taken in 5-min sampling periods from 15 cows (1 cow refused sampling) using a portable, automated, open-circuit gas quantification system (GreenFeed, C-Lock Inc., Rapid City, SD) with intervals of 12h between the 2daily samples. Sampling points were advanced 2h from a day to the next to yield 16 gas samples per cow over 8d to account for diurnal variation in QCH4 and QCO2. The following equations were used sequentially to estimate DMI: (1) heat production (MJ/d)=(4.96 + 16.07 ÷ respiratory quotient) × QCO2; respiratory quotient=0.95; (2) metabolizable energy intake (MJ/d)=(heat production + milk energy) ± tissue energy balance; (3) digestible energy (DE) intake (MJ/d)=metabolizable energy + CH4 energy + urinary energy; (4) gross energy (GE) intake (MJ/d)=DE + [(DE ÷ in vitro true dry matter digestibility) - DE]; and (5) DMI (kg/d)=GE intake estimated ÷ diet GE concentration. Data were analyzed using the MIXED procedure of SAS (SAS Institute Inc., Cary, NC) and Fit Model procedure in JMP (α=0.05; SAS Institute Inc.). Cows significantly differed in DMI measured (23.8 vs. 22.4kg/d for AL and RI, respectively). Dry matter intake estimated using QCH4 and QCO2 coupled with

  10. Optimal beam design on intensity-modulated radiation therapy with simultaneous integrated boost in nasopharyngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Mei-Chun [Division of Radiation Oncology, Department of Oncology Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan (China); Hu, Yu-Wen; Liu, Ching-Sheng [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Lee, Jeun-Shenn [Division of Radiation Oncology, Department of Oncology Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Huang, Pin-I; Yen, Sang-Hue; Lee, Yuh-Lin; Hsieh, Chun-Mei [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Shiau, Cheng-Ying, E-mail: cyshiau@vghtpe.gov.tw [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China)

    2014-10-01

    This study aims to determine the optimal beam design among various combinations of field numbers and beam trajectories for intensity-modulated radiation therapy (IMRT) with simultaneous integrated boost (SIB) technique for the treatment of nasopharyngeal cancer (NPC). We used 10 fields with gantry angles of 155°, 130°, 75°, 25°, 0° L, 0° R, 335°, 285°, 230°, and 205° denoted as F10. To decrease doses in the spinal cord, the F10 technique was designed by featuring 2 pairs of split-opposed beam fields at 155° to 335° and 205° to 25°, as well as one pair of manually split beam fields at 0°. The F10 technique was compared with 4 other common field arrangements: F7E, 7 fields with 50° equally spaced gantry angles; F7, the basis of F10 with 155°, 130°, 75°, 0°, 285°, 230°, and 205°; F9E, 9 fields with 40° equally spaced gantry angles; and FP, 7 posterior fields with 180°, 150°, 120°, 90°, 270°, 240°, and 210°. For each individual case of 10 patients, the customized constraints derived after optimization with the standard F10 technique were applied to 4 other field arrangements. The 4 new optimized plans of each individual case were normalized to achieve the same coverage of planning target volume (PTV){sub 63} {sub Gy} as that of the standard F10 technique. The F10 field arrangement exhibited the best coverage in PTV{sub 70} {sub Gy} and the least mean dose in the trachea-esophagus region. Furthermore, the F10 field arrangement demonstrated the highest level of conformity in the low-dose region and the least monitor unit. The F10 field arrangement performed more outstandingly than the other field arrangements in PTV{sub 70} {sub Gy} coverage and spared the central organ. This arrangement also exhibited the highest conformity and delivery efficiency. The F10 technique is recommended as the standard beam geometry for the SIB-IMRT of NPC.

  11. Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) in nasopharyngeal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Studer, Gabriela [Dept. of Radiation Oncology, Univ. Hospital, Zurich (Switzerland); Peponi, Evangelia; Glanzmann, Christoph; Kunz, Guntram; Renner, Christoph; Tomuschat, Katja

    2010-03-15

    Purpose: To assess the efficacy and safety of using simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) to treat nasopharyngeal cancer (NPC) in a Caucasian cohort. Outcome was analyzed with respect to dose-volume histogram (DVH) values. Patients and Methods: Between 03/2002 and 01/2008, 39 NPC patients underwent SIB-IMRT (37 Caucasians; 31 males; mean age 53 years [16-78 years]). 41% presented with WHO (World Health Organization) type 1 unfavorable histology, 85% with stage III/IV disease. 19 patients had total gross tumor volume (GTV) 16-70 cm{sup 3} (mean 36 cm{sup 3}), while 16 had GTV > 70 cm{sup 3} (73-217 cm{sup 3}; mean 115 cm{sup 3}). All patients with stage II-IV disease received concomitant cisplatin. The prescribed SIB dose delivered to the planning target volume (PTV) was 70 Gy (2.00 Gy/fraction) in 17, 69.6 Gy (2.11 Gy/fraction) in 19, and 66 Gy (2.20 Gy/fraction) in three patients. Results: 3-year local relapse-free, nodal relapse-free, distant metastases-free, disease-free rates and overall survival were 86%, 89%, 85%, 72%, and 85% (median follow-up 30 months [8-71 months]). Histology was a significant prognostic factor concerning overall survival, with worst prognosis in WHO type 1 compared to type 2/3 (75% vs. 93%; p = 0.03). There was a trend in favor of WHO type 2/3 regarding local control (74% vs. 94%; p = 0.052). The PTV DVHs showed a slight left shift compared to reported series. Three patients developed grade 3 late effects (xerostomia [n=2], dysphagia [n=1], hearing loss [n=1]). Conclusion: In comparison with predominantly Asian NPC IMRT series in the literature, chemo-IMRT in the own Caucasian cohort, characterized by less radioresponsive WHO type 1, was equally effective. Treatment tolerance was excellent. (orig.)

  12. {sup 18}F-alfatide PET/CT may predict short-term outcome of concurrent chemoradiotherapy in patients with advanced non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Luan, Xiaohui [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiation Oncology, Jinan, Shandong (China); University of Jinan-Shandong Academy of Medical Sciences, School of Medicine and Life Sciences, Jinan (China); Huang, Yong; Sun, Xiaorong; Ma, Li; Teng, Xuepeng; Lu, Hong [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiology, Jinan, Shandong (China); Gao, Song [Jining Infectious Diseases Hospital, Department of Oncology, Jining, Shandong (China); Wang, Suzhen; Yu, Jinming; Yuan, Shuanghu [Shandong Cancer Hospital affiliated to Shandong University, Department of Radiation Oncology, Jinan, Shandong (China)

    2016-12-15

    The study aims to investigate the role of {sup 18}F-alfatide positron emission tomography/computed tomography (PET/CT) in predicting the short-term outcome of concurrent chemoradiotherapy (CCRT) in patients with advanced non-small cell lung cancer (NSCLC). Eighteen patients with advanced NSCLC had undergone {sup 18}F-alfatide PET/CT scans before CCRT and PET/CT parameters including maximum and mean standard uptake values (SUV{sub max}/SUV{sub mean}), peak standard uptake values (SUV{sub peak}) and tumor volume (TV{sub PET} and TV{sub CT}) were obtained. The SUV{sub max} of tumor and normal tissues (lung, blood pool and muscle) were measured, and their ratios were denoted as T/NT (T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle}). Statistical methods included the Two-example t test, Wilcoxon rank-sum test, Receiver-operating characteristic (ROC) curve analysis and logistic regression analyses. We found that SUV{sub max}, SUV{sub peak}, T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle} were higher in non-responders than in responders (P = 0.0024, P = 0.016, P < 0.001, P = 0.003, P = 0.004). According to ROC curve analysis, the thresholds of SUV{sub max}, SUV{sub peak}, T/NT{sub lung}, T/NT{sub blood} and T/NT{sub muscle} were 5.65, 4.46, 7.11, 5.41, and 11.75, respectively. The five parameters had high sensitivity, specificity and accuracy in distinguishing non-responders and responders. Multivariate logistic regression analyses showed that T/NT{sub lung} was an independent predictor of the short-term outcome of CCRT in patients with advanced NSCLC (P = 0.032). {sup 18}F-alfatide PET/CT may be useful in predicting the short-term outcome of CCRT in patients with advanced NSCLC. (orig.)

  13. Short-Term PTEN Inhibition Improves In Vitro Activation of Primordial Follicles, Preserves Follicular Viability, and Restores AMH Levels in Cryopreserved Ovarian Tissue From Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Edurne Novella-Maestre

    Full Text Available In vitro activation and growth of primordial dormant follicles to produce fertilizable oocytes would provide a useful instrument for fertility preservation. The employment of Phosphatase and TENsin homolog (PTEN inhibitors, in combination with Protein kinase B (Akt stimulating molecules, has been previously employed to increase follicular activation through the stimulation of the PTEN-Akt pathway.We aim to establish improved in vitro activation also for cancer patients whose ovarian tissue has already been cryopreserved. Fresh and previously cryopreserved human ovarian cortex were exposed to short-term, low-concentration and ovary-specific treatment with only a PTEN inhibitor.Our in vitro activation protocol enhances the activation mechanisms of primordial follicles in both fresh and cryopreserved samples, and enlarges growing populations without inducing apoptosis in either follicles or the surrounding stroma. Treatment augments estradiol secretion and restores the expression levels of the previously diminished Anti-Müllerian hormone by means of cryopreservation procedures. Genomic modulation of the relative expression of PTEN pathway genes was found in treated samples.The in vitro activation protocol offers new alternatives for patients with cryopreserved tissue as it increases the pool of viable activated follicles available for in vitro growth procedures. The combination of ovarian tissue cryopreservation and in vitro activation of primordial follicles, the main ovarian reserve component, will be a major advancement in fertility preservation.

  14. Increased range of motion and function in an individual with breast cancer and necrotizing fasciitis-manual therapy and pulsed short-wave diathermy treatment.

    Science.gov (United States)

    Johnson, Wayne; Draper, David O

    2010-01-01

    Necrotizing fasciitis is a severe soft tissue infection of the subcutaneous tissue and fascia affecting those predisposed to immune system compromise. It is a life threatening condition; mortality can be reduced by rapid diagnosis, adequate early surgical debridement and antibiotic ointment. In this case report we present the use of manual therapy (MT) techniques, joint and soft tissue mobilization, following a regimen of pulsed short wave diathermy (PSWD) in the treatment of a woman 3 years post necrotizing fasciitis developed during chemotherapy treatment for breast cancer. During her course of chemotherapy, she developed necrotizing fasciitis which was treated with extensive surgical debridement (8 linear feet of incisions) followed by debridement to both hips and the pelvis area. When we started working with her, we put her on a course of PSWD/MT. After six weeks of following this regimen, she gained 25 degrees of external rotation in both her left and right hips, 15 degrees of left hip flexion and 17 degrees of right hip flexion. The patient gained 10 degrees of right hip extension, yet there was no improvement in left hip extension. The treatments led to a dramatic reduction in pain and scarring from previous surgeries. The patient also returned to running.

  15. An integrated approach utilizing proteomics and bioinformatics to detect ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    YU Jie-kai; ZHENG Shu; TANG Yong; LI Li

    2005-01-01

    Objective: To find new potential biomarkers and establish the patterns for the detection of ovarian cancer. Methods:Sixty one serum samples including 32 ovarian cancer patients and 29 healthy people were detected by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS). The protein fingerprint data were analyzed by bioinformatics tools. Ten folds cross-validation support vector machine (SVM) was used to establish the diagnostic pattern. Results: Five potential biomarkers were found (2085 Da, 5881 Da, 7564 Da, 9422 Da, 6044 Da), combined with which the diagnostic pattern separated the ovarian cancer from the healthy samples with a sensitivity of 96.7%, a specificity of 96.7% and a positive predictive value of96.7%. Conclusions: The combination of SELDI with bioinformatics tools could find new biomarkers and establish patterns with high sensitivity and specificity for the detection of ovarian cancer.

  16. Cost Effectiveness of Integrated Medicine in Patients With Cancer Receiving Anticancer Chemotherapy

    OpenAIRE

    Coriat, Romain; Boudou-Rouquette, Pascaline; Durand, Jean-Philippe; Forgeot d'Arc, Priscille; Martin, Idalie; Mir, Olivier; Ropert, Stanislas; Alexandre, Jérôme; Goldwasser, François

    2012-01-01

    The hospital-home monitoring program is a cost-effective strategy for offering ambulatory chemotherapy treatment to patients with cancer and has become the authors' standard procedure for ambulatory chemotherapy.

  17. Integrated Classification of Prostate Cancer Reveals a Novel Luminal Subtype with Poor Outcome.

    Science.gov (United States)

    You, Sungyong; Knudsen, Beatrice S; Erho, Nicholas; Alshalalfa, Mohammed; Takhar, Mandeep; Al-Deen Ashab, Hussam; Davicioni, Elai; Karnes, R Jeffrey; Klein, Eric A; Den, Robert B; Ross, Ashley E; Schaeffer, Edward M; Garraway, Isla P; Kim, Jayoung; Freeman, Michael R

    2016-09-01

    Prostate cancer is a biologically heterogeneous disease with variable molecular alterations underlying cancer initiation and progression. Despite recent advances in understanding prostate cancer heterogeneity, better methods for classification of prostate cancer are still needed to improve prognostic accuracy and therapeutic outcomes. In this study, we computationally assembled a large virtual cohort (n = 1,321) of human prostate cancer transcriptome profiles from 38 distinct cohorts and, using pathway activation signatures of known relevance to prostate cancer, developed a novel classification system consisting of three distinct subtypes (named PCS1-3). We validated this subtyping scheme in 10 independent patient cohorts and 19 laboratory models of prostate cancer, including cell lines and genetically engineered mouse models. Analysis of subtype-specific gene expression patterns in independent datasets derived from luminal and basal cell models provides evidence that PCS1 and PCS2 tumors reflect luminal subtypes, while PCS3 represents a basal subtype. We show that PCS1 tumors progress more rapidly to metastatic disease in comparison with PCS2 or PCS3, including PSC1 tumors of low Gleason grade. To apply this finding clinically, we developed a 37-gene panel that accurately assigns individual tumors to one of the three PCS subtypes. This panel was also applied to circulating tumor cells (CTC) and provided evidence that PCS1 CTCs may reflect enzalutamide resistance. In summary, PCS subtyping may improve accuracy in predicting the likelihood of clinical progression and permit treatment stratification at early and late disease stages. Cancer Res; 76(17); 4948-58. ©2016 AACR.

  18. Integrated analysis of breast cancer cell lines reveals unique signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Heiser, Laura M.; Wang, Nicholas J.; Talcott, Carolyn L.; Laderoute, Keith R.; Knapp, Merrill; Guan, Yinghui; Hu, Zhi; Ziyad, Safiyyah; Weber, Barbara L.; Laquerre, Sylvie; Jackson, Jeffrey R.; Wooster, Richard F.; Kuo, Wen-Lin; Gray, Joe W.; Spellman, Paul T.

    2009-03-31

    Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EGFR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EGFR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EGFR-MEK signaling. This model was comprised of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype specific subnetworks, including one that suggested PAK1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that PAK1 overexpressing cell lines would have increased sensitivity to MEK inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three MEK inhibitors. We found that PAK1 over-expressing luminal breast cancer cell lines are significantly more sensitive to MEK inhibition as compared to those that express PAK1 at low levels. This indicates that PAK1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to MEK inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.

  19. Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics

    DEFF Research Database (Denmark)

    Khurana, Ekta; Fu, Yao; Colonna, Vincenza;

    2013-01-01

    populations to identify patterns of selection, especially in noncoding regulatory regions. Noncoding regions under very strong negative selection included binding sites of some chromatin and general transcription factors (TFs) and core motifs of some important TF families. Positive selection in TF binding...... sites tended to occur in network hub promoters. Many recurrent somatic cancer variants occurred in noncoding regulatory regions and thus might indicate mutations that drive cancer....

  20. Integrated functional, gene expression and genomic analysis for the identification of cancer targets.

    Directory of Open Access Journals (Sweden)

    Elizabeth Iorns

    Full Text Available The majority of new drug approvals for cancer are based on existing therapeutic targets. One approach to the identification of novel targets is to perform high-throughput RNA interference (RNAi cellular viability screens. We describe a novel approach combining RNAi screening in multiple cell lines with gene expression and genomic profiling to identify novel cancer targets. We performed parallel RNAi screens in multiple cancer cell lines to identify genes that are essential for viability in some cell lines but not others, suggesting that these genes constitute key drivers of cellular survival in specific cancer cells. This approach was verified by the identification of PIK3CA, silencing of which was selectively lethal to the MCF7 cell line, which harbours an activating oncogenic PIK3CA mutation. We combined our functional RNAi approach with gene expression and genomic analysis, allowing the identification of several novel kinases, including WEE1, that are essential for viability only in cell lines that have an elevated level of expression of this kinase. Furthermore, we identified a subset of breast tumours that highly express WEE1 suggesting that WEE1 could be a novel therapeutic target in breast cancer. In conclusion, this strategy represents a novel and effective strategy for the identification of functionally important therapeutic targets in cancer.

  1. 'Integration'

    DEFF Research Database (Denmark)

    Olwig, Karen Fog

    2011-01-01

    After a long history dominated by out-migration, Denmark, Norway and Sweden have, in the past 50 years, become immigration societies. This article compares how these Scandinavian welfare societies have sought to incorporate immigrants and refugees into their national communities. It suggests that......, while the countries have adopted disparate policies and ideologies, differences in the actual treatment and attitudes towards immigrants and refugees in everyday life are less clear, due to parallel integration programmes based on strong similarities in the welfare systems and in cultural notions...... of equality in the three societies. Finally, it shows that family relations play a central role in immigrants’ and refugees’ establishment of a new life in the receiving societies, even though the welfare society takes on many of the social and economic functions of the family....

  2. 一种短期风电功率集成预测方法%An integrated forecasting method of short-term wind power

    Institute of Scientific and Technical Information of China (English)

    张颖超; 郭晓杰; 叶小岭; 邓华

    2016-01-01

    为提高短期风电功率预测精度,缩短模型训练时间,提出了一种短期风电功率集成预测方法。根据风速功率曲线和风速频率特征,将风速划分为高、中、低三段,并对每段的风速功率特征进行统计分析。高、低风速段功率波动较大,使用最小二乘支持向量机(Least Squares Support Vector Machine,LSSVM)方法可取得较高的预测精度。中风速段风速数据点较多,且风速和功率有明显的物理关系,使用高斯(Gaussian)模型预测。并用风速功率等级表对各段预测的结果进行订正,保证了算法的稳定性。用上海某风电场2014年的历史数据,验证了Gaussian模型以及高、中、低风速段对应的预测算法选取的合理性。与LSSVM预测方法相比较,集成预测方法既提高了预测精度又缩短了预测时间,适合风电场短期功率的实时预测。%An integrated forecasting method of short-term wind power is presented for improving prediction accuracy and shortening the model training time. Based on the characteristic of wind power curve and wind speed frequency, the wind speed is divided into high, medium and low three segments, and each wind power characteristic is analyzed. As the predicted power shows larger fluctuated statuses in segments of high and low wind speed, so Least Squares Support Vector Machine is used to achieve better prediction accuracy. Much more data can be accessed in the medium segment, and there is an obvious physical relationship between wind speed and power, so Gaussian Model is used under this sort of circumstance. At the same time, the level table of wind and power is used to revise the predicted power in each section to ensure the stability of the algorithm. The rationality of Gaussian model and selection of algorithm in high, medium and low segment is verified by using the historical data of a wind farm of Shanghai in 2014. The simulated result compared with LSSVM

  3. Identification of genetic determinants of breast cancer immune phenotypes by integrative genome-scale analysis

    Science.gov (United States)

    Simeone, Ines; Anjum, Samreen; Mokrab, Younes; Bertucci, François; Finetti, Pascal; Curigliano, Giuseppe; Cerulo, Luigi; Tomei, Sara; Delogu, Lucia Gemma; Maccalli, Cristina; Miller, Lance D.; Ceccarelli, Michele

    2017-01-01

    ABSTRACT Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development of more effective treatments is hindered by incomplete knowledge of the genetic determinant of immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from The Cancer Genome Atlas (TCGA). By using RNA-sequencing data from 1,004 breast cancers, we defined distinct immune phenotypes characterized by progressive expression of transcripts previously associated with immune-mediated rejection. The T helper 1 (Th-1) phenotype (ICR4), which also displays upregulation of immune-regulatory transcripts such as PDL1, PD1, FOXP3, IDO1, and CTLA4, was associated with prolonged patients' survival. We validated these findings in an independent meta-cohort of 1,954 breast cancer gene expression data. Chromosome segment 4q21, which includes genes encoding for the Th-1 chemokines CXCL9-11, was significantly amplified only in the immune favorable phenotype (ICR4). The mutation and neoantigen load progressively decreased from ICR4 to ICR1 but could not fully explain immune phenotypic differences. Mutations of TP53 were enriched in the immune favorable phenotype (ICR4). Conversely, the presence of MAP3K1 and MAP2K4 mutations were tightly associated with an immune-unfavorable phenotype (ICR1). Using both the TCGA and the validation dataset, the degree of MAPK deregulation segregates breast tumors according to their immune disposition. These findings suggest that mutation-driven perturbations of MAPK pathways are linked to the negative regulation of intratumoral immune response in breast cancer. Modulations of MAPK pathways could be experimentally tested to enhance breast cancer immune sensitivity. PMID:28344865

  4. Custom-Designed MLPA Using Multiple Short Synthetic Probes Application to Methylation Analysis of Five Promoter CpG Islands in Tumor and Urine Specimens from Patients with Bladder Cancer

    DEFF Research Database (Denmark)

    Serizawa, R.R.; Ralfkiaer, U.; Dahl, C.;

    2010-01-01

    -stranded bacteriophage vector to introduce a sequence of defined length between the primer binding site and the specific target sequence. Here we demonstrate that differences in amplicon length can be achieved by using multiple short synthetic probes for each target sequence. When joined by a DNA ligase, these probes...... this assay to analyze DNA from tumor tissue and corresponding urine samples from patients with bladder cancer. Our data show that the use of multiple short synthetic probes provides a simple means for custom-designed MS-MLPA analysis. (J Mol Diagn 2010, 12:402-408; DOI: 10.2353/jmoldx.2010.090152)...

  5. No Evidence That Short-Term Cognitive or Physical Training Programs or Lifestyles Are Related to Changes in White Matter Integrity in Older Adults at Risk of Dementia

    Science.gov (United States)

    Fissler, Patrick; Müller, Hans-Peter; Küster, Olivia C.; Laptinskaya, Daria; Thurm, Franka; Woll, Alexander; Elbert, Thomas; Kassubek, Jan; von Arnim, Christine A. F.; Kolassa, Iris-Tatjana

    2017-01-01

    Cognitive and physical activities can benefit cognition. However, knowledge about the neurobiological mechanisms underlying these activity-induced cognitive benefits is still limited, especially with regard to the role of white matter integrity (WMI), which is affected in cognitive aging and Alzheimer’s disease. To address this knowledge gap, we investigated the immediate and long-term effects of cognitive or physical training on WMI, as well as the association between cognitive and physical lifestyles and changes in WMI over a 6-month period. Additionally, we explored whether changes in WMI underlie activity-related cognitive changes, and estimated the potential of both trainings to improve WMI by correlating training outcomes with WMI. In an observational and interventional pretest, posttest, 3-month follow-up design, we assigned 47 community-dwelling older adults at risk of dementia to 50 sessions of auditory processing and working memory training (n = 13), 50 sessions of cardiovascular, strength, coordination, balance and flexibility exercises (n = 14), or a control group (n = 20). We measured lifestyles trough self-reports, cognitive training skills through training performance, functional physical fitness through the Senior Fitness Test, and global cognition through a cognitive test battery. WMI was assessed via a composite score of diffusion tensor imaging-based fractional anisotropy (FA) of three regions of interest shown to be affected in aging and Alzheimer’s disease: the genu of corpus callosum, the fornix, and the hippocampal cingulum. Effects for training interventions on FA outcomes, as well as associations between lifestyles and changes in FA outcomes were not significant. Additional analyses did show associations between cognitive lifestyle and global cognitive changes at the posttest and the 3-month follow-up (β ≥ 0.40, p ≤ 0.02) and accounting for changes in WMI did not affect these relationships. The targeted training outcomes were

  6. No Evidence That Short-Term Cognitive or Physical Training Programs or Lifestyles Are Related to Changes in White Matter Integrity in Older Adults at Risk of Dementia.

    Science.gov (United States)

    Fissler, Patrick; Müller, Hans-Peter; Küster, Olivia C; Laptinskaya, Daria; Thurm, Franka; Woll, Alexander; Elbert, Thomas; Kassubek, Jan; von Arnim, Christine A F; Kolassa, Iris-Tatjana

    2017-01-01

    Cognitive and physical activities can benefit cognition. However, knowledge about the neurobiological mechanisms underlying these activity-induced cognitive benefits is still limited, especially with regard to the role of white matter integrity (WMI), which is affected in cognitive aging and Alzheimer's disease. To address this knowledge gap, we investigated the immediate and long-term effects of cognitive or physical training on WMI, as well as the association between cognitive and physical lifestyles and changes in WMI over a 6-month period. Additionally, we explored whether changes in WMI underlie activity-related cognitive changes, and estimated the potential of both trainings to improve WMI by correlating training outcomes with WMI. In an observational and interventional pretest, posttest, 3-month follow-up design, we assigned 47 community-dwelling older adults at risk of dementia to 50 sessions of auditory processing and working memory training (n = 13), 50 sessions of cardiovascular, strength, coordination, balance and flexibility exercises (n = 14), or a control group (n = 20). We measured lifestyles trough self-reports, cognitive training skills through training performance, functional physical fitness through the Senior Fitness Test, and global cognition through a cognitive test battery. WMI was assessed via a composite score of diffusion tensor imaging-based fractional anisotropy (FA) of three regions of interest shown to be affected in aging and Alzheimer's disease: the genu of corpus callosum, the fornix, and the hippocampal cingulum. Effects for training interventions on FA outcomes, as well as associations between lifestyles and changes in FA outcomes were not significant. Additional analyses did show associations between cognitive lifestyle and global cognitive changes at the posttest and the 3-month follow-up (β ≥ 0.40, p ≤ 0.02) and accounting for changes in WMI did not affect these relationships. The targeted training outcomes were related

  7. Down-regulation in multiple human cancers of a novel gene, DMHC, from 17q25.1 that encodes an integral membrane protein.

    Science.gov (United States)

    Mikami, I; Harada, H; Nagai, H; Tsuneizumi, M; Nobe, Y; Koizumi, K; Sugano, S; Tanaka, S; Emi, M

    2001-04-01

    Frequent observations of allelic loss in chromosomal band 17q25.1 in a variety of human cancers have suggested that one or more tumor suppressor genes are present in that region. Moreover, a genetic locus for hereditary focal non-epidermolytic palmoplantar keratoderma, a condition associated with cancer of the esophagus (TOC; Tylosis with Oesophageal Cancer), lies in the same region. We screened cell lines derived from a variety of human cancers by reverse transcription-polymerase chain reaction (RT-PCR) to detect alterations in expression of genes within the region in question, by examining expressed sequence tags located there. These experiments identified an 1834-bp full-length cDNA encoding a novel, 441-amino acid integral membrane protein with seven putative transmembrane domains. This gene showed loss or extreme decrease of expression in 6 of 10 uterine cancer-cell lines, 2 of 11 hepatic cell carcinoma-cell lines, 2 of 7 lung cancer-cell lines, 1 of 6 gastric cancer-cell lines, and 1 of 10 breast cancer-cell lines. (We named it DMHC ("down-regulated in multiple human cancers").) Our results suggest that loss of expression of DMHC at 17q25.1 may play an important role in development of variety of human cancers.

  8. Immuno nanoparticles integrated electrical control of targeted cancer cell development using whole cell bioelectronic device.

    Science.gov (United States)

    Hondroulis, Evangelia; Zhang, Rui; Zhang, Chengxiao; Chen, Chunying; Ino, Kosuke; Matsue, Tomokazu; Li, Chen-Zhong

    2014-01-01

    Electrical properties of cells determine most of the cellular functions, particularly ones which occur in the cell's membrane. Manipulation of these electrical properties may provide a powerful electrotherapy option for the treatment of cancer as cancerous cells have been shown to be more electronegative than normal proliferating cells. Previously, we used an electrical impedance sensing system (EIS) to explore the responses of cancerous SKOV3 cells and normal HUVEC cells to low intensity (electric fields, determining that the optimal frequency for SKOV3 proliferation arrest was 200 kHz, without harming the non-cancerous HUVECs. In this study, to determine if these effects are cell type dependant, human breast adenocarcinoma cells (MCF7) were subjected to a range of frequencies (50 kHz-2 MHz) similar to the previously tested SKOV3. For the MCF7, an optimal frequency of 100 kHz was determined using the EIS, indicating a higher sensitivity towards the applied field. Further experiments specifically targeting the two types of cancer cells using HER2 antibody functionalized gold nanoparticles (HER2-AuNPs) were performed to determine if enhanced electric field strength can be induced via the application of nanoparticles, consequently leading to the killing of the cancerous cells without affecting non cancerous HUVECs and MCF10a providing a platform for the development of a non-invasive cancer treatment without any harmful side effects. The EIS was used to monitor the real-time consequences on cellular viability and a noticeable decrease in the growth profile of the MCF7 was observed with the application of the HER2-AuNPs and the electric fields indicating specific inhibitory effects on dividing cells in culture. To further understand the effects of the externally applied field to the cells, an Annexin V/EthD-III assay was performed to determine the cell death mechanism indicating apoptosis. The zeta potential of the SKOV3 and the MCF7 before and after incorporation of

  9. Integrated proteo-genomic approach for early diagnosis and prognosis of cancer.

    Science.gov (United States)

    Shukla, Hem D; Mahmood, Javed; Vujaskovic, Zeljko

    2015-12-01

    Cancer is the leading cause of mortality among men and women worldwide. Despite the availability of numerous diagnostic techniques for various cancers, the overall survival rate remains low and the majority of patients die due to late diagnosis and advanced stage of the disease. Diagnosing and treating cancer at its early stages ideally during the precancerous phase could significantly increase survival rate with the possibility of cure and prolong survival. Cancer is a genetic disease and it is illicitly activated by the acquisition of somatic DNA lesions and aberrations in genome structure and defects in maintenance and repair. These somatic DNA mutations known as driver mutations seem to be the prime cause in initiating tumorigenesis. The advances in genomic technologies have immensely facilitated the understanding of cancer progression and metastasis, and the discovery of novel biomarkers. However, changes in somatic mutational landscape of the oncogenome are translated into aberrantly regulated oncoproteome which drives the cancer initiation. Thus, combination of proteomic and genomic technologies is urgently required to discover biomarkers for early diagnosis. The recent advances in human genome based detection of cancer using advanced genomic technologies like NextGen Sequencing, digital PCR, cfDNA technology have shown promise; for example oncogenic somatic mutation variants, transcriptomic analysis, copy number variant, and methylation data from the Cancer Genome Atlas. Similarly, oncoproteomics has the potential to revolutionize clinical management of the disease, including cancer diagnosis and screening based on new proteomic database which embodies somatic variants and post translational modifications, thus devising proteomic technologies as a complement to histopathology. Further, the use of multiple proteomic and genomic biomarkers rather than a single gene or protein could greatly improve diagnostic accuracy and enhance the predictive power for

  10. Integration of co-localized glandular morphometry and protein biomarker expression in immunofluorescent images for prostate cancer prognosis

    Science.gov (United States)

    Scott, Richard; Khan, Faisal M.; Zeineh, Jack; Donovan, Michael; Fernandez, Gerardo

    2015-03-01

    Immunofluorescent (IF) image analysis of tissue pathology has proven to be extremely valuable and robust in developing prognostic assessments of disease, particularly in prostate cancer. There have been significant advances in the literature in quantitative biomarker expression as well as characterization of glandular architectures in discrete gland rings. However, while biomarker and glandular morphometric features have been combined as separate predictors in multivariate models, there is a lack of integrative features for biomarkers co-localized within specific morphological sub-types; for example the evaluation of androgen receptor (AR) expression within Gleason 3 glands only. In this work we propose a novel framework employing multiple techniques to generate integrated metrics of morphology and biomarker expression. We demonstrate the utility of the approaches in predicting clinical disease progression in images from 326 prostate biopsies and 373 prostatectomies. Our proposed integrative approaches yield significant improvements over existing IF image feature metrics. This work presents some of the first algorithms for generating innovative characteristics in tissue diagnostics that integrate co-localized morphometry and protein biomarker expression.

  11. Regulators of genetic risk of breast cancer identified by integrative network analysis.

    Science.gov (United States)

    Castro, Mauro A A; de Santiago, Ines; Campbell, Thomas M; Vaughn, Courtney; Hickey, Theresa E; Ross, Edith; Tilley, Wayne D; Markowetz, Florian; Ponder, Bruce A J; Meyer, Kerstin B

    2016-01-01

    Genetic risk for breast cancer is conferred by a combination of multiple variants of small effect. To better understand how risk loci might combine, we examined whether risk-associated genes share regulatory mechanisms. We created a breast cancer gene regulatory network comprising transcription factors and groups of putative target genes (regulons) and asked whether specific regulons are enriched for genes associated with risk loci via expression quantitative trait loci (eQTLs). We identified 36 overlapping regulons that were enriched for risk loci and formed a distinct cluster within the network, suggesting shared biology. The risk transcription factors driving these regulons are frequently mutated in cancer and lie in two opposing subgroups, which relate to estrogen receptor (ER)(+) luminal A or luminal B and ER(-) basal-like cancers and to different luminal epithelial cell populations in the adult mammary gland. Our network approach provides a foundation for determining the regulatory circuits governing breast cancer, to identify targets for intervention, and is transferable to other disease settings.

  12. Short tunnels.

    NARCIS (Netherlands)

    Schreuder, D.A.

    1965-01-01

    Before dealing with the question of lighting short tunnels, it is necessary define what is meant by a tunnel and when it should be called 'short'. Confined to motorized road traffic the following is the most apt definition of a tunnel: every form of roofing-over a road section, irrespective of it le

  13. The technologically integrated oncosimulator: combining multiscale cancer modeling with information technology in the in silico oncology context.

    Science.gov (United States)

    Stamatakos, Georgios; Dionysiou, Dimitra; Lunzer, Aran; Belleman, Robert; Kolokotroni, Eleni; Georgiadi, Eleni; Erdt, Marius; Pukacki, Juliusz; Rüeping, Stefan; Giatili, Stavroula; d'Onofrio, Alberto; Sfakianakis, Stelios; Marias, Kostas; Desmedt, Christine; Tsiknakis, Manolis; Graf, Norbert

    2014-05-01

    This paper outlines the major components and function of the technologically integrated oncosimulator developed primarily within the Advancing Clinico Genomic Trials on Cancer (ACGT) project. The Oncosimulator is defined as an information technology system simulating in vivo tumor response to therapeutic modalities within the clinical trial context. Chemotherapy in the neoadjuvant setting, according to two real clinical trials concerning nephroblastoma and breast cancer, has been considered. The spatiotemporal simulation module embedded in the Oncosimulator is based on the multiscale, predominantly top-down, discrete entity-discrete event cancer simulation technique developed by the In Silico Oncology Group, National Technical University of Athens. The technology modules include multiscale data handling, image processing, invocation of code execution via a spreadsheet-inspired environment portal, execution of the code on the grid, and the visualization of the predictions. A refining scenario for the eventual coupling of the oncosimulator with immunological models is also presented. Parameter values have been adapted to multiscale clinical trial data in a consistent way, thus supporting the predictive potential of the oncosimulator. Indicative results demonstrating various aspects of the clinical adaptation and validation process are presented. Completion of these processes is expected to pave the way for the clinical translation of the system.

  14. Integrated analyses identify a master microRNA regulatory network for the mesenchymal subtype in serous ovarian cancer.

    Science.gov (United States)

    Yang, Da; Sun, Yan; Hu, Limei; Zheng, Hong; Ji, Ping; Pecot, Chad V; Zhao, Yanrui; Reynolds, Sheila; Cheng, Hanyin; Rupaimoole, Rajesha; Cogdell, David; Nykter, Matti; Broaddus, Russell; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Liu, Jinsong; Shmulevich, Ilya; Sood, Anil K; Chen, Kexin; Zhang, Wei

    2013-02-11

    Integrated genomic analyses revealed a miRNA-regulatory network that further defined a robust integrated mesenchymal subtype associated with poor overall survival in 459 cases of serous ovarian cancer (OvCa) from The Cancer Genome Atlas and 560 cases from independent cohorts. Eight key miRNAs, including miR-506, miR-141, and miR-200a, were predicted to regulate 89% of the targets in this network. Follow-up functional experiments illustrate that miR-506 augmented E-cadherin expression, inhibited cell migration and invasion, and prevented TGFβ-induced epithelial-mesenchymal transition by targeting SNAI2, a transcriptional repressor of E-cadherin. In human OvCa, miR-506 expression was correlated with decreased SNAI2 and VIM, elevated E-cadherin, and beneficial prognosis. Nanoparticle delivery of miR-506 in orthotopic OvCa mouse models led to E-cadherin induction and reduced tumor growth.

  15. Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Chung Jae

    2009-06-01

    Full Text Available Abstract Background Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s underlying the development of platinum resistance in late-stage ovarian cancer patients currently remains unknown, CpG-island (CGI methylation, a phenomenon strongly associated with aberrant gene silencing and ovarian tumorigenesis, may contribute to this devastating condition. Methods To model the onset of drug resistance, and investigate DNA methylation and gene expression alterations associated with platinum resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation and mRNA expression microarray analyses. To identify chemoresistance-associated, biological pathways likely impacted by DNA methylation, promoter CGI methylation and mRNA expression profiles were integrated and subjected to pathway enrichment analysis. Results Promoter CGI methylation revealed a positive association (Spearman correlation of 0.99 between the total number of hypermethylated CGIs and GI50 values (i.e., increased drug resistance following successive cisplatin treatment cycles. In accord with that result, chemoresistance was reversible by DNA methylation inhibitors. Pathway enrichment analysis revealed hypermethylation-mediated repression of cell adhesion and tight junction pathways and hypomethylation-mediated activation of the cell growth-promoting pathways PI3K/Akt, TGF-beta, and cell cycle progression, which may contribute to the onset of chemoresistance in ovarian cancer cells. Conclusion Selective epigenetic disruption of distinct biological

  16. Integrated miRNA-risk gene-pathway pair network analysis provides prognostic biomarkers for gastric cancer

    Directory of Open Access Journals (Sweden)

    Cai H

    2016-05-01

    Full Text Available Hui Cai,1 Jiping Xu,2 Yifang Han,3 Zhengmao Lu,1 Ting Han,1 Yibo Ding,4 Liye Ma1 1Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 2Department of Medical Administration, Changhai Hospital, Second Military Medical University, Shanghai, 3Department of Epidemiology, Research Institute for Medicine of Nanjing Command, Nanjing, 4Department of Epidemiology, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China Purpose: This study aimed to identify molecular prognostic biomarkers for gastric cancer. Methods: mRNA and miRNA expression profiles of eligible gastric cancer and control samples were downloaded from Gene Expression Omnibus to screen the differentially expressed genes (DEGs and differentially expressed miRNAs (DEmiRs, using MetaDE and limma packages, respectively. Target genes of the DEmiRs were also collected from both predictive and experimentally validated target databases of miRNAs. The overlapping genes between selected targets and DEGs were identified as risk genes, followed by functional enrichment analysis. Human pathways and their corresponding genes were downloaded from the Kyoto Encyclopedia of Genes and Genomes (KEGG database for the expression analysis of each pathway in gastric cancer samples. Next, co-pathway pairs were selected according to the Pearson correlation coefficients. Finally, the co-pathway pairs, miRNA–target pairs, and risk gene–pathway pairs were merged into a complex interaction network, the most important nodes (miRNAs/target genes/co-pathway pairs of which were selected by calculating their degrees.Results: Totally, 1,260 DEGs and 144 DEmiRs were identified. There were 336 risk genes found in the 9,572 miRNA–target pairs. Judging from the pathway expression files, 45 co-pathway pairs were screened out. There were 1,389 interactive pairs and 480 nodes in the integrated network. Among all nodes in the network, focal

  17. Short-chain fatty acid level and field cancerization show opposing associations with enteroendocrine cell number and neuropilin expression in patients with colorectal adenoma

    Directory of Open Access Journals (Sweden)

    Staton Carolyn A

    2011-03-01

    Full Text Available Abstract Background Previous reports have suggested that the VEGF receptor neuropilin-1 (NRP-1 is expressed in a singly dispersed subpopulation of cells in the normal colonic epithelium, but that expression becomes dysregulated during colorectal carcinogenesis, with higher levels in tumour suggestive of a poor prognosis. We noted that the spatial distribution and morphology if NRP-1 expressing cells resembles that of enteroendocrine cells (EEC which are altered in response to disease state including cancer and irritable bowel syndrome (IBS. We have shown that NRP-1 is down-regulated by butyrate in colon cancer cell lines in vitro and we hypothesized that butyrate produced in the lumen would have an analogous effect on the colon mucosa in vivo. Therefore we sought to investigate whether NRP-1 is expressed in EEC and how NRP-1 and EEC respond to butyrate and other short-chain fatty acids (SCFA - principally acetate and propionate. Additionally we sought to assess whether there is a field effect around adenomas. Methodology Biopsies were collected at the mid-sigmoid, at the adenoma and at the contralateral wall (field of 28 subjects during endoscopy. Samples were fixed for IHC and stained for either NRP-1 or for chromogranin A (CgA, a marker of EEC. Stool sampling was undertaken to assess individuals' butyrate, acetate and propionate levels. Result NRP-1 expression was inversely related to SCFA concentration at the colon landmark (mid-sigmoid, but expression was lower and not related to SCFA concentration at the field. Likewise CgA+ cell number was also inversely related to SCFA at the landmark, but was lower and unresponsive at the field. Crypt cellularity was unaltered by field effect. A colocalisation analysis showed only a small subset of NRP-1 localised with CgA. Adenomas showed extensive, weaker staining for NRP-1 which contrastingly correlated positively with butyrate level. Field effects cause this relationship to be lost. Adenoma tissue

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

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    Jaeyun Sung

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

  19. CLINICAL EXPERIENCE OF CANCER IMMUNOTHERAPY INTEGRATED WITH OLEIC ACID COMPLEXED WITH DE-GLYCOSYLATED VITAMIN D BINDING PROTEIN

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    Emma Ward

    2014-01-01

    Full Text Available Proteins highly represented in milk such as α-lactalbumin and lactoferrin bind Oleic Acid (OA to form complexes with selective anti-tumor activity. A protein present in milk, colostrum and blood, vitamin D binding protein is the precursor of a potent Macrophage Activating Factor (GcMAF and in analogy with other OA-protein complexes, we proposed that OA-GcMAF could demonstrate a greater immunotherapeutic activity than that of GcMAF alone. We describe a preliminary experience treating patients with advanced cancers, often labelled as “incurable” with an integrative immunotherapy centred on OA-GcMAF. Patients with advanced cancer were treated at the Immuno Biotech Treatment Centre with OA-GcMAF-based integrative immunotherapy in combination with a very low carbohydrate, high protein diet, fermented milk products containing naturally produced GcMAF, vitamin D3 and low-dose acetylsalicylic acid. When the primary tumor or a metastasis could be measured by ultrasonographic techniques, we observed, on average, a decrease of tumor volume of approximately 25% in a week. We also observed a consistent increase in splenic blood flow that was interpreted in the context of generalised immune system activation and allowed to assess the degree of responsiveness of the individual patient. The results reported here are consistent with the results previously described in the experimental animal harbouring a human hepatocellular carcinoma as well as with the results reported for neoadjuvant chemotherapy. OA-protein complexes are bound to play a leading role in cancer therapy thanks to selectivity of antitumoral effects, absence of any side effects, safety and oral availability. We hypothesise that OA-GcMAF, combines the known anticancer effects OA-protein complexes with the well established immune stimulating effects of GcMAF.

  20. Very short-term reactive forecasting of the solar ultraviolet index using an extreme learning machine integrated with the solar zenith angle.

    Science.gov (United States)

    Deo, Ravinesh C; Downs, Nathan; Parisi, Alfio V; Adamowski, Jan F; Quilty, John M

    2017-02-18

    Exposure to erythemally-effective solar ultraviolet radiation (UVR) that contributes to malignant keratinocyte cancers and associated health-risk is best mitigated through innovative decision-support systems, with global solar UV index (UVI) forecast necessary to inform real-time sun-protection behaviour recommendations. It follows that the UVI forecasting models are useful tools for such decision-making. In this study, a model for computationally-efficient data-driven forecasting of diffuse and global very short-term reactive (VSTR) (10-min lead-time) UVI, enhanced by drawing on the solar zenith angle (θs) data, was developed using an extreme learning machine (ELM) algorithm. An ELM algorithm typically serves to address complex and ill-defined forecasting problems. UV spectroradiometer situated in Toowoomba, Australia measured daily cycles (0500-1700h) of UVI over the austral summer period. After trialling activations functions based on sine, hard limit, logarithmic and tangent sigmoid and triangular and radial basis networks for best results, an optimal ELM architecture utilising logarithmic sigmoid equation in hidden layer, with lagged combinations of θs as the predictor data was developed. ELM's performance was evaluated using statistical metrics: correlation coefficient (r), Willmott's Index (WI), Nash-Sutcliffe efficiency coefficient (ENS), root mean square error (RMSE), and mean absolute error (MAE) between observed and forecasted UVI. Using these metrics, the ELM model's performance was compared to that of existing methods: multivariate adaptive regression spline (MARS), M5 Model Tree, and a semi-empirical (Pro6UV) clear sky model. Based on RMSE and MAE values, the ELM model (0.255, 0.346, respectively) outperformed the MARS (0.310, 0.438) and M5 Model Tree (0.346, 0.466) models. Concurring with these metrics, the Willmott's Index for the ELM, MARS and M5 Model Tree models were 0.966, 0.942 and 0.934, respectively. About 57% of the ELM model's absolute

  1. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  2. Scapula alata in early breast cancer patients enrolled in a randomized clinical trial of post-surgery short-course image-guided radiotherapy

    Directory of Open Access Journals (Sweden)

    Adriaenssens Nele

    2012-05-01

    Full Text Available Abstract Background Scapula alata (SA is a known complication of breast surgery associated with palsy of the serratus anterior, but it is seldom mentioned. We evaluated the risk factors associated with SA and the relationship of SA with ipsilateral shoulder/arm morbidity in a series of patients enrolled in a trial of post-surgery radiotherapy (RT. Methods The trial randomized women with completely resected stage I-II breast cancer to short-course image-guided RT, versus conventional RT. SA, arm volume and shoulder-arm mobility were measured prior to RT and at one to three months post-RT. Shoulder/arm morbidities were computed as a post-RT percentage change relative to pre-RT measurements. Results Of 119 evaluable patients, 13 (= 10.9% had pre-RT SA. Age younger than 50 years old, a body mass index less than 25 kg/m2, and axillary lymph node dissection were significant risk factors, with odds ratios of 4.8 (P = 0.009, 6.1 (P = 0.016, and 6.1 (P = 0.005, respectively. Randomization group was not significant. At one to three months’ post-RT, mean arm volume increased by 4.1% (P = 0.036 and abduction decreased by 8.6% (P = 0.046 among SA patients, but not among non-SA patients. SA resolved in eight, persisted in five, and appeared in one patient. Conclusion The relationship of SA with lower body mass index suggests that SA might have been underestimated in overweight patients. Despite apparent resolution of SA in most patients, pre-RT SA portended an increased risk of shoulder/arm morbidity. We argue that SA warrants further investigation. Incidentally, the observation of SA occurring after RT in one patient represents the second case of post-RT SA reported in the literature.

  3. Peripheral myeloid-derived suppressor and T regulatory PD-1 positive cells predict response to neoadjuvant short-course radiotherapy in rectal cancer patients.

    Science.gov (United States)

    Napolitano, Maria; D'Alterio, Crescenzo; Cardone, Eleonora; Trotta, Anna Maria; Pecori, Biagio; Rega, Daniela; Pace, Ugo; Scala, Dario; Scognamiglio, Giosuè; Tatangelo, Fabiana; Cacciapuoti, Carmela; Pacelli, Roberto; Delrio, Paolo; Scala, Stefania

    2015-04-10

    Short-course preoperative radiotherapy (SC-RT) followed by total mesorectal excision (TME) is one therapeutic option for locally advanced rectal cancer (LARC) patients. Since radio-induced DNA damage may affect tumor immunogenicity, Myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) were evaluated in 13 patients undergoing SC-RT and TME for LARC. Peripheral Granulocytic-MDSCs (G-MDSC) [LIN-/HLA-DR-/CD11b+/CD14-/CD15+/CD33+], Monocytic (M-MDSC) [CD14+/HLA-DR-/lowCD11b+/CD33+] and Tregs [CD4+/CD25hi+/FOXP3+- CTLA-4/PD1] basal value was significantly higher in LARC patients compared to healthy donors (HD). Peripheral MDSC and Tregs were evaluated at time 0 (T0), after 2 and 5 weeks (T2-T5) from radiotherapy; before surgery (T8) and 6-12 months after surgery (T9, T10). G-MDSC decreased at T5 and further at T8 while M-MDSC cells decreased at T5; Tregs reached the lowest value at T5. LARC poor responder patients displayed a major decrease in M-MDSC after SC-RT and an increase of Treg-PD-1. In this pilot study MDSCs and Tregs decrease during the SC-RT treatment could represent a biomarker of response in LARC patients. Further studies are needed to confirm that the deepest M-MDSC reduction and increase in Treg-PD1 cells within 5-8 weeks from the beginning of treatment could discriminate LARC patients poor responding to SC-RT.

  4. Integration of Nuclear- and Extranuclear-Initiated Estrogen Receptor Signaling in Breast Cancer Cells

    Science.gov (United States)

    Madak Erdogan, Zeynep

    2009-01-01

    Estrogenic hormones exert their effects through binding to Estrogen Receptors (ERs), which work in concert with coregulators and extranuclear signaling pathways to control gene expression in normal as well as cancerous states, including breast tumors. In this thesis, we have used multiple genome-wide analysis tools to elucidate various ways that…

  5. Cancer treatment as a game: integrating evolutionary game theory into the optimal control of chemotherapy.

    Science.gov (United States)

    Orlando, Paul A; Gatenby, Robert A; Brown, Joel S

    2012-12-01

    Chemotherapy for metastatic cancer commonly fails due to evolution of drug resistance in tumor cells. Here, we view cancer treatment as a game in which the oncologists choose a therapy and tumors 'choose' an adaptive strategy. We propose the oncologist can gain an upper hand in the game by choosing treatment strategies that anticipate the adaptations of the tumor. In particular, we examine the potential benefit of exploiting evolutionary tradeoffs in tumor adaptations to therapy. We analyze a math model where cancer cells face tradeoffs in allocation of resistance to two drugs. The tumor 'chooses' its strategy by natural selection and the oncologist chooses her strategy by solving a control problem. We find that when tumor cells perform best by investing resources to maximize response to one drug the optimal therapy is a time-invariant delivery of both drugs simultaneously. However, if cancer cells perform better using a generalist strategy allowing resistance to both drugs simultaneously, then the optimal protocol is a time varying solution in which the two drug concentrations negatively covary. However, drug interactions can significantly alter these results. We conclude that knowledge of both evolutionary tradeoffs and drug interactions is crucial in planning optimal chemotherapy schedules for individual patients.

  6. Integrative approach to pre-operative determination of clinically significant prostate cancer

    Directory of Open Access Journals (Sweden)

    Shatylko T.V.

    2015-09-01

    Full Text Available Aim: improvement of early diagnostics of prostate cancer by developing a technique, which makes possible to predict its clinical significance in outpatient setting before initiation of invasive procedures. Material and Methods. Clinical data of 398 patients who underwent transrectal prostate biopsy in 2012-2014 in SSMU S. R. Mirotvortsev Clinical Hospital, was used to build an artificial neural network, while its output allowed to determine whether the tumour corresponds to Epstein criteria and which D'Amico risk group it belongs to. Internal validation was performed on 80 patients, who underwent prostate biopsy in September 2014 — December 2014. Sensitivity, specificity, positive and negative predictive value of artificial neural network were calculated. Results. Accuracy of predicting adenocarcinoma presence in biopsy specimen was 93,75%; accuracy of predicting whether the cancer meets active surveillance criteria was 90%. Accuracy of predicting T stage (T1c, T2a, T2b, T2cwas 57,1%. Prediction of D'Amico risk group was accurate in 70% of cases; for low-risk cancer accuracy was 81,2%. Conclusion. Artificial neural networks may be responsible for prostate cancer risk stratification and determination of its clinical significance prior to biopsy.

  7. Tailoring folic acid and methotrexate-attributed quantum dots for integrated cancer cell imaging and therapy

    Science.gov (United States)

    Fahmi, Mochamad Zakki; Chang, Jia-Yaw

    2016-03-01

    Potential application of folic acid and methotrexate-attributed AgInS2-ZnS quantum dots on both detection and therapeutic of cancer cell were intensively investigated on this study. In the initial step, the bright luminescent of QDs, with % QY up to 55.3, were synthesized with one-pot two-step process resulting narrow particle distribution and successfully transferred to water phase without significant effect on optical properties. The water-soluble AgInS2-ZnS quantum dots (QDs) encapsulated with oleylamine have been successfully prepared by ultrasonication assisting. Several aspect including QDs characterization, pH stability, ionic strength, and bonding properties were investigated to reach desired condition of water-soluble AgInS2-ZnS QDs. Folic acid was further conjugated to QDs for HeLa and MCF7 cancer cell imaging to performs the targeting capability. Moreover, folic acid is efficiently internalized into cell through the receptor-mediated endocytosis even when conjugated with a wide variety of molecules. Confocal imaging characterization further informs folic acid-conjugated AgInS2-ZnS QDs could most specific targeted to the human cervical (HeLa) cells. The therapeutic feature of QDs on HeLa cancer cell was conjugated by attributing methotrexate on the QDs, instead of folic acid, and the design could improve on inhibiting the cancer cell viability as well as its fluorescent intensity.

  8. Cancer treatment as a game: integrating evolutionary game theory into the optimal control of chemotherapy

    Science.gov (United States)

    Orlando, Paul A.; Gatenby, Robert A.; Brown, Joel S.

    2012-12-01

    Chemotherapy for metastatic cancer commonly fails due to evolution of drug resistance in tumor cells. Here, we view cancer treatment as a game in which the oncologists choose a therapy and tumors ‘choose’ an adaptive strategy. We propose the oncologist can gain an upper hand in the game by choosing treatment strategies that anticipate the adaptations of the tumor. In particular, we examine the potential benefit of exploiting evolutionary tradeoffs in tumor adaptations to therapy. We analyze a math model where cancer cells face tradeoffs in allocation of resistance to two drugs. The tumor ‘chooses’ its strategy by natural selection and the oncologist chooses her strategy by solving a control problem. We find that when tumor cells perform best by investing resources to maximize response to one drug the optimal therapy is a time-invariant delivery of both drugs simultaneously. However, if cancer cells perform better using a generalist strategy allowing resistance to both drugs simultaneously, then the optimal protocol is a time varying solution in which the two drug concentrations negatively covary. However, drug interactions can significantly alter these results. We conclude that knowledge of both evolutionary tradeoffs and drug interactions is crucial in planning optimal chemotherapy schedules for individual patients.

  9. Integrated Multimodal Imaging of Dynamic Bone-Tumor Alterations Associated with Metastatic Prostate Cancer

    NARCIS (Netherlands)

    Brisset, Jean-Christophe; Hoff, Benjamin A.; Chenevert, Thomas L.; Jacobson, Jon A.; Boes, Jennifer L.; Galban, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D.; Pienta, Kenneth J.; Galban, Craig J.; Meyer, Charles R.; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S.; Hussain, Maha; Ross, Brian D.; Schakel, Tim

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellul

  10. Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration

    NARCIS (Netherlands)

    M. Smid (Marcel); F.G. Rodriguez-Gonzalez (F. German); A.M. Sieuwerts (Anieta); R. Salgado (Roberto); W.J.C. Prager-van der Smissen (Wendy); Vlugt-Daane, M.V.D. (Michelle Van Der); A. van Galen (Anne); S. Nik-Zainal (Serena); J. Staaf (Johan); A.B. Brinkman (Arie B.); M.J. Vijver (Marc ); A.L. Richardson (Andrea); A. Fatima (Aquila); Berentsen, K. (Kim); A. Butler (Adam); S. Martin (Sandra); H. Davies (Helen); J.E.M.A. Debets (Reno); M.E.M.-V. Gelder (Marion E. Meijer-Van); C.H.M. van Deurzen (Carolien); Macgrogan, G. (Gaëtan); Van Den Eynden, G.G.G.M. (Gert G. G. M.); C.A. Purdie (Colin A.); A.M. Thompson (Alastair M.); C. Caldas (Carlos); P.N. Span (Paul); Simpson, P.T. (Peter T.); S. Lakhani (Sunil); S.J. van Laere (Steven); C. Desmedt (Christine); Ringnér, M. (Markus); Tommasi, S. (Stefania); Eyford, J. (Jorunn); A. Broeks (Annegien); A. Vincent-Salomon (Anne); Futreal, P.A. (P. Andrew); S. Knappskog (Stian); King, T. (Tari); G. Thomas (Gilles); Viari, A. (Alain); Langerød, A. (Anita); A.-L. Borresen-Dale (Anne-Lise); E. Birney (Ewan); H. Stunnenberg (Henk); M.R. Stratton (Michael); J.A. Foekens (John); J.W.M. Martens (John)

    2016-01-01

    textabstractA recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP

  11. Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration

    NARCIS (Netherlands)

    Smid, M.; Rodriguez-Gonzalez, F.G.; Sieuwerts, A.M.; Salgado, R.; Smissen, W.J. Prager-Van der; Vlugt-Daane, M.V.; Galen, A. van; Nik-Zainal, S.; Staaf, J.; Brinkman, A.B.; Vijver, M.J. van de; Richardson, A.L.; Fatima, A.; Berentsen, K.; Butler, A.; Martin, S.; Davies, H.R.; Debets, R.; Gelder, M.E. Meijer-van; Deurzen, C.H. van; MacGrogan, G.; Eynden, G.G. Van den; Purdie, C.; Thompson, A.M.; Caldas, C.; Span, P.N; Simpson, P.T.; Lakhani, S.R.; Laere, S. van; Desmedt, C.; Ringner, M.; Tommasi, S.; Eyford, J.; Broeks, A.; Vincent-Salomon, A.; Futreal, P.A.; Knappskog, S.; King, T.; Thomas, G; Viari, A.; Langerod, A.; Borresen-Dale, A.L.; Birney, E.; Stunnenberg, H.G.; Stratton, M.; Foekens, J.A.; Martens, J.W.M.

    2016-01-01

    A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA,

  12. Integrating proteomic and functional genomic technologies in discovery-driven translational breast cancer research

    DEFF Research Database (Denmark)

    Celis, Julio E; Gromov, Pavel; Gromova, Irina

    2003-01-01

    The application of state-of-the-art proteomics and functional genomics technologies to the study of cancer is rapidly shifting toward the analysis of clinically relevant samples derived from patients, as the ultimate aim of translational research is to bring basic discoveries closer to the bedsid...

  13. An integrative model on the role of DMBT1 in epithelial cancer

    DEFF Research Database (Denmark)

    Mollenhauer, Jan; Helmke, Burkhard; Müller, Hanna

    2002-01-01

    The gene, deleted in malignant brain tumors 1 (DMBT1), has been proposed to play a role in brain and epithelial cancer, but shows unusual features for a classical tumor suppressor gene. We have proposed that its presumptive dual function in protection and differentiation is of importance to under...

  14. Return-to-work interventions integrated into cancer care: a systematic review

    NARCIS (Netherlands)

    Tamminga, S.J.; de Boer, A.G.E.M.; Verbeek, J.H.A.M.; Frings-Dresen, M.H.W.

    2010-01-01

    Objectives The purpose of this study was to review the literature on the content of interventions focusing on return to work, employment status, or work retention in patients with cancer. Furthermore, the effect of the interventions on return to work was assessed in studies reporting return to work.

  15. Religiousness/Spirituality, Cardiovascular Disease, and Cancer: Cultural Integration for Health Research and Intervention

    Science.gov (United States)

    Masters, Kevin S.; Hooker, Stephanie A.

    2013-01-01

    Objective: Recently, behavioral scientists have developed greater interest in understanding the relations between religiousness and spirituality (R/S) and health. Our objectives were to (a) provide an overview of the R/S and health literature specific to cardiovascular disease (CVD) and cancer, (b) discuss the importance of religious culture…

  16. Integrated Analysis of Genome-Wide Copy Number Alterations and Gene Expression Profiling of Lung Cancer in Xuanwei, China

    Science.gov (United States)

    Zhang, Yanliang; Xue, Qiuyue; Pan, Guoqing; Meng, Qing H.; Tuo, Xiaoyu; Cai, Xuemei; Chen, Zhenghui; Li, Ya; Huang, Tao; Duan, Xincen; Duan, Yong

    2017-01-01

    Objectives Lung cancer in Xuanwei (LCXW), China, is known throughout the world for its distinctive characteristics, but little is known about its pathogenesis. The purpose of this study was to screen potential novel “driver genes” in LCXW. Methods Genome-wide DNA copy number alterations (CNAs) were detected by array-based comparative genomic hybridization and differentially expressed genes (DEGs) by gene expression microarrays in 8 paired LCXW and non-cancerous lung tissues. Candidate driver genes were screened by integrated analysis of CNAs and DEGs. The candidate genes were further validated by real-time quantitative polymerase chain reaction. Results Large numbers of CNAs and DEGs were detected, respectively. Some of the most frequently occurring CNAs included gains at 5p15.33-p15.32, 5p15.1-p14.3, and 5p14.3-p14.2 and losses at 11q24.3, 21q21.1, 21q22.12-q22.13, and 21q22.2. Integrated analysis of CNAs and DEGs identified 24 candidate genes with frequent copy number gains and concordant upregulation, which were considered potential oncogenes, including CREB3L4, TRIP13, and CCNE2. In addition, the analysis identified 19 candidate genes with a negative association between copy number change and expression change, considered potential tumor suppressor genes, including AHRR, NKD2, and KLF10. One of the most studied oncogenes, MYC, may not play a carcinogenic role in LCXW. Conclusions This integrated analysis of CNAs and DEGs identified several potential novel LCXW-related genes, laying an important foundation for further research on the pathogenesis of LCXW and identification of novel biomarkers or therapeutic targets. PMID:28056099

  17. Classical pathology and mutational load of breast cancer - integration of two worlds.

    Science.gov (United States)

    Budczies, Jan; Bockmayr, Michael; Denkert, Carsten; Klauschen, Frederick; Lennerz, Jochen K; Györffy, Balázs; Dietel, Manfred; Loibl, Sibylle; Weichert, Wilko; Stenzinger, Albrecht

    2015-10-01

    Breast cancer is a complex molecular disease comprising several biological subtypes. However, daily routine diagnosis is still based on a small set of well-characterized clinico-pathological variables. Here, we try to link the two worlds of surgical pathology and multilayered molecular profiling by analyzing the relationships between clinico-pathological phenotypes and mutational loads of breast cancer. We evaluated the number of mutated genes with somatic non-silent mutations in different subgroups of breast cancer based on clinico-pathological, including immunohistochemical and tumour characteristics. The analysis was performed for a cohort of 687 primary breast cancer patients with mutational profiling, gene expression and clinico-pathological data available from The Cancer Genome Atlas (TCGA) project. The number of mutated genes was strongly positively associated with higher tumour grade (p = 1.4e-14) and with the different immunohistochemical and PAM50 molecular subtypes of breast cancer (p = 1.4e-10 and p = 4.3e-10, respectively). We observed significant associations (|R| > 0.4) between the abundance of mutated genes and expression levels of genes related to proliferation in the overall cohort and hormone receptor positive cohort, including the Recurrence Score gene signature (e.g., MYBL2 and BIRC5). Specific mutated genes (TP53, NCOR1, NF1, PTPRD and RB1) were highly significantly associated with high loads of mutated genes. Multivariate analysis for overall survival (OS) revealed a worse survival for patients with high numbers of mutated genes (hazard ratio = 4.6, 95% CI: 1.0 - 20.0, p = 0.044). Here, we report a strong association of the number of mutated genes with immunohistochemical and PAM50 subtypes and tumour grade in breast cancer. We provide evidence that specific levels of the mutational load underlie different morphological and biological phenotypes, which collectively constitute the current basis of pathological diagnosis

  18. Cationic lipid guided short-hairpin RNA interference of annexin A2 attenuates tumor growth and metastasis in a mouse lung cancer stem cell model.

    Science.gov (United States)

    Andey, Terrick; Marepally, Srujan; Patel, Apurva; Jackson, Tanise; Sarkar, Shubhashish; O'Connell, Malaney; Reddy, Rakesh C; Chellappan, Srikumar; Singh, Pomila; Singh, Mandip

    2014-06-28

    The role of side populations (SP) or cancer stem-like cells (CSC) in promoting the resistance phenotype presents a viable anticancer target. Human-derived H1650 SP cells over-express annexin A2 (AnxA2) and SOX2, and are resistant to conventional cytotoxic chemotherapeutics. AnxA2 and SOX2 bind to proto-oncogenes, c-Myc and c-Src, and AnxA2 forms a functional heterotetramer with S100A10 to promote tumor motility. However, the combined role of AnxA2, S100A10 and SOX2 in promoting the resistant phenotype of SP cells has not been investigated. In the current studies, we examined for the first time a possible role of AnxA2 in regulating SA100A10 and SOX2 in promoting a resistant phenotype of lung tumors derived from H1650 SP cells. The resistance of H1650 SP cells to chemotherapy compared to H1650 MP cells was investigated by cell viability studies. A short hairpin RNA targeting AnxA2 (shAnxA2) was formulated in a liposomal (cationic ligand-guided, CLG) carrier and characterized for size, charge and entrapment and loading efficiencies; CLG carrier uptake by H1650 SP cells was demonstrated by fluorescence microscopy, and knockdown of AnxA2 confirmed by qRT-PCR and Western blot. Targeting of xenograft and orthotopic lung tumors was demonstrated with fluorescent (DiR) CLG carriers in mice. The therapeutic efficacy of CLG-AnxA2, compared to that of placebo, was investigated after 2 weeks of treatment in terms of tumor weights and tumor burden in vivo. Compared to mixed population cells, H1650 SP cells showed exponential resistance to docetaxel (15-fold), cisplatin (13-fold), 5-fluorouracil (31-fold), camptothecin (7-fold), and gemcitabine (16-fold). CLG carriers were nanoparticulate (199nm) with a slight positive charge (21.82mV); CLG-shAnx2 was of similar size (217nm) with decreased charge (12.11mV), and entrapment and loading efficiencies of 97% and 6.13% respectively. Fluorescence microscopy showed high uptake of CLG-shAnxA2 in H1650 SP cells after 2h resulting in a 6

  19. INCREASED RISK OF THROMBOEMBOLISM AS A RESULT OF HIGH THROMBIN PRODUCTION IS ASSOCIATED WITH SHORT ACTIVATED PARTIAL THROMBOPLASTIN TIME IN CANCER PATIENTS ON AND AFTER CHEMOTHERAPY: A PROSPECTIVE STUDY IN A TERTIARY CARE HOSPITAL

    Directory of Open Access Journals (Sweden)

    Indranil

    2014-06-01

    Full Text Available : To investigate wheather cancer patients during and following chemotherapy with short activated partial thromboplastin times (aPTTs have increased thrombin generation and are at increased risk for thromboembolism, this prospective study was designed. Routine coagulation specimens of such patients were screened for the presence of short or normal aPTT for 5-month period, and, accordingly, 250 specimens were collected. Prothrombin fragment F1+2 (F1+2 was measured to evaluate thrombin activation, and a second aPTT was performed with a different reagent. Clinical history were obtained from medical records after conclusion of sample collection. 6 to12months later, patients were questioned on thromboembolic events during the previous 18 months by questionnaire. F1+2 and the incidence of venous thromboses were elevated significantly in the short aPTT group. Patients with acute bleeding had short aPTTs, but 36% of these also had thromboembolic events during the 18 months proximal to blood collection. These findings were confirmed with the second aPTT reagent. Patients with short aPTTs have increased thrombin generation and are at increased risk for thromboembolism, mainly venous thromboses, despite the fact that a short aPTT can occur in the acute setting of bleeding.

  20. Beyond androgen deprivation: ancillary integrative strategies for targeting the androgen receptor addiction of prostate cancer.

    Science.gov (United States)

    McCarty, Mark F; Hejazi, Jalal; Rastmanesh, Reza

    2014-09-01

    The large majority of clinical prostate cancers remain dependent on androgen receptor (AR) activity for proliferation even as they lose their responsiveness to androgen deprivation or antagonism. AR activity can be maintained in these circumstances by increased AR synthesis--often reflecting increased NF-κB activation; upregulation of signaling pathways that promote AR activity in the absence of androgens; and by emergence of AR mutations or splice variants lacking the ligand-binding domain, which render the AR constitutively active. Drugs targeting the N-terminal transactivating domain of the AR, some of which are now in preclinical development, can be expected to inhibit the activity not only of unmutated ARs but also of the mutant forms and splice variants selected for by androgen deprivation. Concurrent measures that suppress AR synthesis or boost AR turnover could be expected to complement the efficacy of such drugs. A number of nutraceuticals that show efficacy in prostate cancer xenograft models--including polyphenols from pomegranate, grape seed, and green tea, the crucifera metabolite diindolylmethane, and the hormone melatonin--have the potential to suppress AR synthesis via downregulation of NF-κB activity; clinical doses of salicylate may have analogous efficacy. The proteasomal turnover of the AR is abetted by diets with a high ratio of long-chain omega-3 to omega-6 fatty acids, which are beneficial in prostate cancer xenograft models; berberine and sulforaphane, by inhibiting AR's interaction with its chaperone Hsp90, likewise promote AR proteasomal degradation and retard growth of human prostate cancer in nude mice. Hinge region acetylation of the AR is required for optimal transactivational activity, and low micromolar concentrations of the catechin epigallocatechin-3-gallate (EGCG) can inhibit such acetylation--possibly explaining the ability of EGCG administration to suppress androgenic activity and cell proliferation in prostate cancer

  1. [Montérégie Comprehensive Cancer Care Centre: integrating nurse navigators in Montérégie's oncology teams: one aspect of implementing the Cancer Control Program--Part 1].

    Science.gov (United States)

    Plante, Anne; Joannette, Sonia

    2009-01-01

    The oncology patient navigator role was developed to ensure both continuity and consultation in the delivery of care to cancer patients and their families. In Québec, this role is filled by a nurse. This first article in a series of two, aims to explain why nurses were selected as patient navigators and to describe how this new role has been integrated in the Montérégie Region. The Québec Cancer Control Program, the definition established for the oncology nurse navigator role and the implementation of an integrated care network based on the Montérégie experience will be discussed.

  2. Model-integrated estimation of normal tissue contamination for cancer SNP allelic copy number data.

    Science.gov (United States)

    Stjernqvist, Susann; Rydén, Tobias; Greenman, Chris D

    2011-01-01

    SNP allelic copy number data provides intensity measurements for the two different alleles separately. We present a method that estimates the number of copies of each allele at each SNP position, using a continuous-index hidden Markov model. The method is especially suited for cancer data, since it includes the fraction of normal tissue contamination, often present when studying data from cancer tumors, into the model. The continuous-index structure takes into account the distances between the SNPs, and is thereby appropriate also when SNPs are unequally spaced. In a simulation study we show that the method performs favorably compared to previous methods even with as much as 70% normal contamination. We also provide results from applications to clinical data produced using the Affymetrix genome-wide SNP 6.0 platform.

  3. Designing a broad-spectrum integrative approach for cancer prevention and treatment

    OpenAIRE

    2015-01-01

    Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that a...

  4. Critical questions in metastatic castration-resistant prostate cancer: Integrating emerging clinical evidence and guideline recommendations

    OpenAIRE

    2016-01-01

    Metastatic castration-resistant prostate cancer (CRPC) typically confers a poor prognosis, however, novel advances in treatment options, as well as biomarkers for monitoring disease response and progression, have recently helped improve survival rates. Additionally, new guidelines provide some direction on incorporating these new treatments but some confusion still exists among clinicians about best methods for initiating treatment and the optimal sequencing of agents to prolong survival. In ...

  5. Emerging integrated nanoclay-facilitated drug delivery system for papillary thyroid cancer therapy

    Science.gov (United States)

    Zhang, Yi; Long, Mei; Huang, Peng; Yang, Huaming; Chang, Shi; Hu, Yuehua; Tang, Aidong; Mao, Linfeng

    2016-09-01

    Nanoclay can be incorporated into emerging dual functional drug delivery systems (DDSs) to promote efficiency in drug delivery and reduce the toxicity of doxorubicin (DOX) used for thyroid cancer treatment. This paper reports the expansion of the basal spacing of kaolinite nanoclay was expanded from 0.72 nm to 0.85 nm, which could provide sufficiently spacious site for hosting doxorubicin molecules and controlling the diffusion rate. A targeted design for papillary thyroid cancer cells was achieved by introducing KI, which is consumed by the sodium-iodide symporter (NIS). As indicated by MTT assays, confocal laser scanning microscopy and bio-TEM observations, methoxy-intercalated kaolinite (KaolinMeOH) exhibited negligible cytotoxicity against papillary thyroid cancer cells. By contrast, DOX-KaolinMeOH showed dose-dependent therapeutic effects in vitro, and KI@DOX-KaolinMeOH was found to act as a powerful targeted therapeutic drug. Furthermore, active and passive targeting strategies played a role in the accumulation of the drug molecules, as verified by an in vivo bio-distribution analysis.

  6. Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 Induces Loss of Epithelial Integrity

    Directory of Open Access Journals (Sweden)

    Fei Yao

    2015-07-01

    Full Text Available Genome rearrangements, a hallmark of cancer, can result in gene fusions with oncogenic properties. Using DNA paired-end-tag (DNA-PET whole-genome sequencing, we analyzed 15 gastric cancers (GCs from Southeast Asians. Rearrangements were enriched in open chromatin and shaped by chromatin structure. We identified seven rearrangement hot spots and 136 gene fusions. In three out of 100 GC cases, we found recurrent fusions between CLDN18, a tight junction gene, and ARHGAP26, a gene encoding a RHOA inhibitor. Epithelial cell lines expressing CLDN18-ARHGAP26 displayed a dramatic loss of epithelial phenotype and long protrusions indicative of epithelial-mesenchymal transition (EMT. Fusion-positive cell lines showed impaired barrier properties, reduced cell-cell and cell-extracellular matrix adhesion, retarded wound healing, and inhibition of RHOA. Gain of invasion was seen in cancer cell lines expressing the fusion. Thus, CLDN18-ARHGAP26 mediates epithelial disintegration, possibly leading to stomach H+ leakage, and the fusion might contribute to invasiveness once a cell is transformed.

  7. Immunotherapy in castration-resistant prostate cancer: integrating sipuleucel-T into our current treatment paradigm.

    Science.gov (United States)

    Garcia, Jorge A; Dreicer, Robert

    2011-03-01

    The availability of several novel antibodies, coupled with viral, DNA, and dendritic-cell vaccines, has renewed interest in immunotherapeutic approaches to the treatment of advanced prostate cancer. Although promising, none of these approaches have led to major clinical activity, and in the case of cell-based immunotherapy with GVAX, new concerns about safety arose when this therapy was used in the castration-resistant setting. A more attractive yet toxic approach has also utilized a check-point blockade with CTLA-4 antibodies. Although initial clinical efficacy has been observed, toxicity appears to be the major limitation of its use in prostate cancer. Sipuleucel-T (Provenge) is an autologous active cellular immunotherapy product that includes autologous dendritic cells pulsed ex vivo with PAP2024, a recombinant fusion protein made of prostatic acid phosphataase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Despite the lack of objective anti-tumor activity seen with sipuleucel-T, a recently reported phase III trial demonstrated a significant improvement in the overall survival of men with asymptomatic, minimally symptomatic metastatic castration-resistant prostate cancer (CRPC). This agent is the first FDA-approved novel immunotherapeutic compound for the treatment of a solid malignancy. A better understanding of how clinicians should incorporate this novel agent into the current management of CRPC is needed.

  8. The development of an integrated platform to identify breast cancer glycoproteome changes in human serum.

    Science.gov (United States)

    Zeng, Zhi; Hincapie, Marina; Haab, Brian B; Hanash, Samir; Pitteri, Sharon J; Kluck, Steven; Hogan, Jason M; Kennedy, Jacob; Hancock, William S

    2010-05-07

    Protein glycosylation represents one of the major post-translational modifications and can have significant effects on protein function. Moreover, changes in the carbohydrate structure are increasingly being recognized as an important modification associated with cancer etiology. In this report, we describe the development of a proteomics approach to identify breast cancer related changes in either concentration and/or the carbohydrate structures of glycoprotein(s) present in blood samples. Diseased and healthy serum samples were processed by an optimized sample preparation protocol using multiple lectin affinity chromatography (M-LAC) that partitions serum proteins based on glycan characteristics. Subsequently, three separate procedures, 1D SDS-PAGE, isoelectric focusing and an antibody microarray, were applied to identify potential candidate markers for future study. The combination of these three platforms is illustrated in this report with the analysis of control and cancer glycoproteomic fractions. Firstly, a molecular weight based separation of glycoproteins by 1D SDS-PAGE was performed, followed by protein, glycoprotein staining, lectin blotting and LC-MS analysis. To refine or confirm the list of interesting glycoproteins, isoelectric focusing (targeting sialic acid changes) and an antibody microarray (used to detect neutral glycan shifts) were selected as the orthogonal methods. As a result, several glycoproteins including alpha-1B-glycoprotein, complement C3, alpha-1-antitrypsin and transferrin were identified as potential candidates for further study.

  9. Key nodes of a microRNA network associated with the integrated mesenchymal subtype of high-grade serous ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Yan Sun; Da Yang; Wei Zhang; Fei Guo; Marina Bagnoli; Feng-Xia Xue; Bao-Cun Sun; Ilya Shmulevich; Delia Mezzanzanica; Ke-Xin Chen; Anil K. Sood

    2015-01-01

    Metastasis is the main cause of cancer mortality. One of the initiating events of cancer metastasis of epithelial tumors is epithelial-to-mesenchymal transition (EMT), during which cells dedifferentiate from a relatively rigid cell structure/morphology to a flexible and changeable structure/morphology often associated with mesenchymal cells. The presence of EMT in human epithelial tumors is reflected by the increased expression of genes and levels of proteins that are preferentialy present in mesenchymal cels. The combined presence of these genes forms the basis of mesenchymal gene signatures, which are the foundation for classifying a mesenchymal subtype of tumors. Indeed, tumor classification schemes that use clustering analysis of large genomic characterizations, like The Cancer Genome Atlas (TCGA), have defined mesenchymal subtype in a number of cancer types, such as high-grade serous ovarian cancer and glioblastoma. However, recent analyses have shown that gene expression-based classifications of mesenchymal subtypes often do not associate with poor survival. This“paradox” can be ameliorated using integrated analysis that combines multiple data types. We recently found that integrating mRNA and microRNA (miRNA) data revealed an integrated mesenchymal subtype that is consistently associated with poor survival in multiple cohorts of patients with serous ovarian cancer. This network consists of 8 major miRNAs and 214 mRNAs. Among the 8 miRNAs, 4 are known to be regulators of EMT. This review provides a summary of these 8 miRNAs, which were associated with the integrated mesenchymal subtype of serous ovarian cancer.

  10. Integrating diet and exercise into care of prostate cancer patients on androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Moyad MA

    2016-08-01

    Full Text Available Mark A Moyad,1 Robert U Newton,2 Ulf W Tunn,3 Damian Gruca4 1Department of Urology, University of Michigan Medical Center, Ann Arbor, MI, USA; 2Exercise Medicine Research Institute, Edith Cowan University, Joondalup, WA, Australia; 3Urological Clinic, Facharztzentrum Academic Hospital Sana Klinikum Offenbach, Offenbach/Main, 4Global Medical Affairs, AbbVie Deutschland, Ludwigshafen, Germany Abstract: Improved diagnosis and treatment regimens have resulted in greater longevity for men with prostate cancer. This has led to an increase in both androgen deprivation therapy (ADT use and duration of exposure, and therefore to its associated adverse effects, such as sexual dysfunction, osteoporosis, reduced muscle mass, increased fat mass, and increased incidence of cardiovascular disease and type 2 diabetes. Given that the adverse effects of ADT are systemic, often debilitating, and difficult to treat, efforts continue in the development of new strategies for long-term management of prostate cancer. The PubMed database was searched to select trials, reviews, and meta-analyses in English using such search terms as “prostate cancer” and “androgen deprivation therapy”, “cardiovascular risk”, “lean body mass”, “exercise”, and “diet”. The initial searches produced 379 articles with dates 2005 or more recent. Articles published after 2004 were favored. This review utilizes the latest data to provide a status update on the effects of exercise and diet on patients with prostate cancer, focusing on ADT-associated side effects, and it discusses the evidence for such interventions. Since the evidence of large-scale trials in patients with prostate cancer is missing, and an extrapolation of supporting data to all patient subgroups cannot be provided, individualized risk assessments remain necessary before the initiation of exercise and diet programs. Exercise, diet, and nutritional supplementation interventions have the potential to

  11. Integrative identification of deregulated miRNA/TF-mediated gene regulatory loops and networks in prostate cancer.

    Science.gov (United States)

    Afshar, Ali Sobhi; Xu, Joseph; Goutsias, John

    2014-01-01

    MicroRNAs (miRNAs) have attracted a great deal of attention in biology and medicine. It has been hypothesized that miRNAs interact with transcription factors (TFs) in a coordinated fashion to play key roles in regulating signaling and transcriptional pathways and in achieving robust gene regulation. Here, we propose a novel integrative computational method to infer certain types of deregulated miRNA-mediated regulatory circuits at the transcriptional, post-transcriptional and signaling levels. To reliably predict miRNA-target interactions from mRNA/miRNA expression data, our method collectively utilizes sequence-based miRNA-target predictions obtained from several algorithms, known information about mRNA and miRNA targets of TFs available in existing databases, certain molecular structures identified to be statistically over-represented in gene regulatory networks, available molecular subtyping information, and state-of-the-art statistical techniques to appropriately constrain the underlying analysis. In this way, the method exploits almost every aspect of extractable information in the expression data. We apply our procedure on mRNA/miRNA expression data from prostate tumor and normal samples and detect numerous known and novel miRNA-mediated deregulated loops and networks in prostate cancer. We also demonstrate instances of the results in a number of distinct biological settings, which are known to play crucial roles in prostate and other types of cancer. Our findings show that the proposed computational method can be used to effectively achieve notable insights into the poorly understood molecular mechanisms of miRNA-mediated interactions and dissect their functional roles in cancer in an effort to pave the way for miRNA-based therapeutics in clinical settings.

  12. Gadolinium(III)-Chelated Silica Nanospheres Integrating Chemotherapy and Photothermal Therapy for Cancer Treatment and Magnetic Resonance Imaging.

    Science.gov (United States)

    Cao, Mingjing; Wang, Pengyang; Kou, Yu; Wang, Jing; Liu, Jing; Li, Yanhui; Li, Jiayang; Wang, Liming; Chen, Chunying

    2015-11-18

    The combination of therapy and diagnosis has been emerging as a promising strategy for cancer treatment. To realize chemotherapy, photothermal therapy, and magnetic resonance imaging (MRI) in one system, we have synthesized a new magnetic nanoparticle (Gd@SiO2-DOX/ICG-PDC) integrating doxorubicin (DOX), indocyanine green (ICG), and gadolinium(III)-chelated silica nanospheres (Gd@SiO2) with a poly(diallyldimethylammonium chloride) (PDC) coating. PDC coating serves as a polymer layer to protect from quick release of drugs from the nanocarriers and increase cellular uptake. The DOX release from Gd@SiO2-DOX/ICG-PDC depends on pH and temperature. The process will be accelerated in the acidic condition than in a neutral pH 7.4. Meanwhile, upon laser irradiation, the photothermal effects promote DOX release and improve the therapeutic efficacy compared to either DOX-loaded Gd@SiO2 or ICG-loaded Gd@SiO2. Moreover, MRI results show that the Gd@SiO2-PDC nanoparticles are safe T1-type MRI contrast agents for imaging. The Gd@SiO2-PDC nanoparticles loaded with DOX and ICG can thus act as a promising theranostic platform for multimodal cancer treatment.

  13. Non-pharmacological interventions to manage fatigue and psychological stress in children and adolescents with cancer: an integrative review.

    Science.gov (United States)

    Lopes-Júnior, L C; Bomfim, E O; Nascimento, L C; Nunes, M D R; Pereira-da-Silva, G; Lima, R A G

    2016-11-01

    Cancer-related fatigue (CRF) is the most stressful and prevalent symptom in paediatric oncology patients. This integrative review aimed to identify, analyse and synthesise the evidence of non-pharmacological intervention studies to manage fatigue and psychological stress in a paediatric population with cancer. Eight electronic databases were used for the search: PubMed, Web of Science, CINAHL, LILACS, EMBASE, SCOPUS, PsycINFO and the Cochrane Library. Initially, 273 articles were found; after the exclusion of repeated articles, reading of the titles, abstracts and the full articles, a final sample of nine articles was obtained. The articles were grouped into five categories: physical exercise, healing touch, music therapy, therapeutic massage, nursing interventions and health education. Among the nine studies, six showed statistical significance regarding the fatigue and/or stress levels, showing that the use of the interventions led to symptoms decrease. The most frequently tested intervention was programmed physical exercises. It is suggested that these interventions are complementary to conventional treatment and that their use can indicate an improvement in CRF and psychological stress.

  14. Impact of integration of clinical and outpatient units on cancer patient satisfaction

    NARCIS (Netherlands)

    Wessels, H.; De Graeff, A.; Groenewegen, G.; Wynia, K.; De Heus, M.; Vos, J. B. H.; Tjia, P.; Kruitwagen, C. L. J. J.; Teunissen, S. C. C. M.; Voest, Emile E.

    2010-01-01

    There is an ongoing drive to measure and improve quality of care. Donabedians' quality framework with structure, process and outcome domains provides a useful hold to examine quality of care. The aim of this study was to address the effect of an intervention in hospital structure (integration of thr

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

    Directory of Open Access Journals (Sweden)

    Luca Grieco

    2013-10-01

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

  16. A Broad-Spectrum Integrative Design for Cancer Prevention and Therapy

    Science.gov (United States)

    Block, Keith I.; Gyllenhaal, Charlotte; Lowe, Leroy; Amedei, Amedeo; Amin, A.R.M. Ruhul; Amin, Amr; Aquilano, Katia; Arbiser, Jack; Arreola, Alexandra; Arzumanyan, Alla; Ashraf, S. Salman; Azmi, Asfar S.; Benencia, Fabian; Bhakta, Dipita; Bilsland, Alan; Bishayee, Anupam; Blain, Stacy W.; Block, Penny B.; Boosani, Chandra S.; Carey, Thomas E.; Carnero, Amancio; Carotenuto, Marianeve; Casey, Stephanie C.; Chakrabarti, Mrinmay; Chaturvedi, Rupesh; Chen, Georgia Zhuo; Chen, Helen; Chen, Sophie; Chen, Yi Charlie; Choi, Beom K.; Ciriolo, Maria Rosa; Coley, Helen M.; Collins, Andrew R.; Connell, Marisa; Crawford, Sarah; Curran, Colleen S.; Dabrosin, Charlotta; Damia, Giovanna; Dasgupta, Santanu; DeBerardinis, Ralph J.; Decker, William K.; Dhawan, Punita; Diehl, Anna Mae E.; Dong, Jin-Tang; Dou, Q. Ping; Drew, Janice E.; Elkord, Eyad; El-Rayes, Bassel; Feitelson, Mark A.; Felsher, Dean W.; Ferguson, Lynnette R; Fimognari, Carmela; Firestone, Gary L.; Frezza, Christian; Fujii, Hiromasa; Fuster, Mark M.; Generali, Daniele; Georgakilas, Alexandros G.; Gieseler, Frank; Gilbertson, Michael; Green, Michelle F.; Grue, Brendan; Guha, Gunjan; Halicka, Dorota; Helferich, William G.; Heneberg, Petr; Hentosh, Patricia; Hirschey, Matthew D.; Hofseth, Lorne J.; Holcombe, Randall F.; Honoki, Kanya; Hsu, Hsue-Yin; Huang, Gloria S.; Jensen, Lasse D.; Jiang, Wen G.; Jones, Lee W.; Karpowicz, Phillip A.; Keith, W Nicol; Kerkar, Sid P.; Khan, Gazala N.; Khatami, Mahin; Ko, Young H.; Kucuk, Omer; Kulathinal, Rob J.; Kumar, Nagi B.; Kumara, H.M.C. Shantha; Kwon, Byoung S.; Le, Anne; Lea, Michael A.; Lee, Ho-Young; Lichtor, Terry; Lin, Liang-Tzung; Locasale, Jason W.; Lokeshwar, Bal L.; Longo, Valter D.; Lyssiotis, Costas A.; MacKenzie, Karen L.; Malhotra, Meenakshi; Marino, Maria; Martinez-Chantar, Maria L.; Matheu, Ander; Maxwell, Christopher; McDonnell, Eoin; Meeker, Alan K.; Mehrmohamadi, Mahya; Mehta, Kapil; Michelotti, Gregory A.; Mohammad, Ramzi M.; Mohammed, Sulma I.; Morre, D. James; Muqbil, Irfana; Muralidhar, Vinayak; Murphy, Michael P.; Nagaraju, Ganji Purnachandra; Nahta, Rita; Niccolai, Elena; Nowsheen, Somaira; Panis, Carolina; Pantano, Francesco; Parslow, Virginia R.; Pawelec, Graham; Pedersen, Peter L.; Poore, Brad; Poudyal, Deepak; Prakash, Satya; Prince, Mark; Raffaghello, Lizzia; Rathmell, Jeffrey C.; Rathmell, W. Kimryn; Ray, Swapan K.; Reichrath, Jörg; Rezazadeh, Sarallah; Ribatti, Domenico; Ricciardiello, Luigi; Robey, R. Brooks; Rodier, Francis; Rupasinghe, H.P. Vasantha; Russo, Gian Luigi; Ryan, Elizabeth P.; Samadi, Abbas K.; Sanchez-Garcia, Isidro; Sanders, Andrew J.; Santini, Daniele; Sarkar, Malancha; Sasada, Tetsuro; Saxena, Neeraj K.; Shackelford, Rodney E; Sharma, Dipali; Shin, Dong M.; Sidransky, David; Siegelin, Markus David; Signori, Emanuela; Singh, Neetu; Sivanand, Sharanya; Sliva, Daniel; Smythe, Carl; Spagnuolo, Carmela; Stafforini, Diana M.; Stagg, John; Subbarayan, Pochi R.; Sundin, Tabetha; Talib, Wamidh H.; Thompson, Sarah K.; Tran, Phuoc T.; Ungefroren, Hendrik; Vander Heiden, Matthew G.; Venkateswaran, Vasundara; Vinay, Dass S.; Vlachostergios, Panagiotis J.; Wang, Zongwei; Wellen, Kathryn E.; Whelan, Richard L.; Yang, Eddy S.; Yang, Huanjie; Yang, Xujuan; Yaswen, Paul; Yedjou, Clement; Yin, Xin; Zhu, Jiyue; Zollo, Massimo

    2016-01-01

    Targeted therapies and the consequent adoption of “personalized” oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity “broad-spectrum” therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested; many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment. Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to help us address disease relapse, which is a

  17. Critical questions in metastatic castration-resistant prostate cancer: Integrating emerging clinical evidence and guideline recommendations

    Directory of Open Access Journals (Sweden)

    Mohamed Ali

    2016-01-01

    Full Text Available Metastatic castration-resistant prostate cancer (CRPC typically confers a poor prognosis, however, novel advances in treatment options, as well as biomarkers for monitoring disease response and progression, have recently helped improve survival rates. Additionally, new guidelines provide some direction on incorporating these new treatments but some confusion still exists among clinicians about best methods for initiating treatment and the optimal sequencing of agents to prolong survival. In this article, we review the literature and answer some frequently asked questions about treating men with metastatic CRPC, including choosing a first-line treatment, monitoring treatment response, and proceeding to additional lines of therapy.

  18. Rationale, design, and implementation protocol of the Dutch clinical practice guideline Pain in patients with cancer: a cluster randomised controlled trial with short message service (SMS and interactive voice response (IVR

    Directory of Open Access Journals (Sweden)

    te Boveldt Nienke

    2011-12-01

    Full Text Available Abstract Background One-half of patients with cancer have pain. In nearly one out of two cancer patients with pain, this was undertreated. Inadequate pain control still remains an important problem in this group of patients. Therefore, in 2008 a national, evidence-based multidisciplinary clinical practice guideline 'pain in patients with cancer' has been developed. Yet, publishing a guideline is not enough. Implementation is needed to improve pain management. An innovative implementation strategy, Short Message Service with Interactive Voice Response (SVS-IVR, has been developed and pilot tested. This study aims to evaluate on effectiveness of this strategy to improve pain reporting, pain measurement and adequate pain therapy. In addition, whether the active role of the patient and involvement of caregivers in pain management may change. Methods/design A cluster randomised controlled trial with two arms will be performed in six oncology outpatient clinics of hospitals in the Southeastern region of the Netherlands, with three hospitals in the intervention and three in the control condition. Follow-up measurements will be conducted in all hospitals to study the long-term effect of the intervention. The intervention includes training of professionals (medical oncologists, nurses, and general practitioners and SMS-IVR to report pain in patients with cancer to improve pain reporting by patients, pain management by medical oncologists, nurses, and general practitioners, and decrease pain intensity. Discussion This innovative implementation strategy with technical tools and the involvement of patients, may enhance the use of the guideline 'pain in patients with cancer' for pain management. Short Message Service alerts may serve as a tool to support self-management of patients. Therefore, the SMS-IVR intervention may increase the feeling of having control over one's life. Trail registration Netherlands Trial Register (NTR: NTR2739

  19. Retrospective feasibility study of simultaneous integrated boost in cervical cancer using tomotherapy: the impact of organ motion and tumor regression

    Directory of Open Access Journals (Sweden)

    Herrera Fernanda G

    2013-01-01

    Full Text Available Abstract Background Whole pelvis intensity modulated radiotherapy (IMRT is increasingly being used to treat cervical cancer aiming to reduce side effects. Encouraged by this, some groups have proposed the use of simultaneous integrated boost (SIB to target the tumor, either to get a higher tumoricidal effect or to replace brachytherapy. Nevertheless, physiological organ movement and rapid tumor regression throughout treatment might substantially reduce any benefit of this approach. Purpose To evaluate the clinical target volume - simultaneous integrated boost (CTV-SIB regression and motion during chemo-radiotherapy (CRT for cervical cancer, and to monitor treatment progress dosimetrically and volumetrically to ensure treatment goals are met. Methods and materials Ten patients treated with standard doses of CRT and brachytherapy were retrospectively re-planned using a helical Tomotherapy - SIB technique for the hypothetical scenario of this feasibility study. Target and organs at risk (OAR were contoured on deformable fused planning-computed tomography and megavoltage computed tomography images. The CTV-SIB volume regression was determined. The center of mass (CM was used to evaluate the degree of motion. The Dice’s similarity coefficient (DSC was used to assess the spatial overlap of CTV-SIBs between scans. A cumulative dose-volume histogram modeled estimated delivered doses. Results The CTV-SIB relative reduction was between 31 and 70%. The mean maximum CM change was 12.5, 9, and 3 mm in the superior-inferior, antero-posterior, and right-left dimensions, respectively. The CTV-SIB-DSC approached 1 in the first week of treatment, indicating almost perfect overlap. CTV-SIB-DSC regressed linearly during therapy, and by the end of treatment was 0.5, indicating 50% discordance. Two patients received less than 95% of the prescribed dose. Much higher doses to the OAR were observed. A multiple regression analysis showed a significant interaction

  20. Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration.

    Science.gov (United States)

    Smid, Marcel; Rodríguez-González, F Germán; Sieuwerts, Anieta M; Salgado, Roberto; Prager-Van der Smissen, Wendy J C; Vlugt-Daane, Michelle van der; van Galen, Anne; Nik-Zainal, Serena; Staaf, Johan; Brinkman, Arie B; van de Vijver, Marc J; Richardson, Andrea L; Fatima, Aquila; Berentsen, Kim; Butler, Adam; Martin, Sancha; Davies, Helen R; Debets, Reno; Gelder, Marion E Meijer-Van; van Deurzen, Carolien H M; MacGrogan, Gaëtan; Van den Eynden, Gert G G M; Purdie, Colin; Thompson, Alastair M; Caldas, Carlos; Span, Paul N; Simpson, Peter T; Lakhani, Sunil R; Van Laere, Steven; Desmedt, Christine; Ringnér, Markus; Tommasi, Stefania; Eyford, Jorunn; Broeks, Annegien; Vincent-Salomon, Anne; Futreal, P Andrew; Knappskog, Stian; King, Tari; Thomas, Gilles; Viari, Alain; Langerød, Anita; Børresen-Dale, Anne-Lise; Birney, Ewan; Stunnenberg, Hendrik G; Stratton, Mike; Foekens, John A; Martens, John W M

    2016-09-26

    A recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP53, PIK3CA, PTEN, CCND1 and CDH1. We find that CCND3 expression levels do not correlate with amplification, while increased GATA3 expression in mutant GATA3 cancers suggests GATA3 is an oncogene. In luminal cases the total number of substitutions, irrespective of type, associates with cell cycle gene expression and adverse outcome, whereas the number of mutations of signatures 3 and 13 associates with immune-response specific gene expression, increased numbers of tumour-infiltrating lymphocytes and better outcome. Thus, while earlier reports imply that the sheer number of somatic aberrations could trigger an immune-response, our data suggests that substitutions of a particular type are more effective in doing so than others.

  1. The integration of anthracyclines in the treatment of advanced ovarian cancer.

    Science.gov (United States)

    Lück, H J; Du Bois, A; Weber, B; Pfisterer, J; Goupil, A; Kuhn, W; Barats, J C; Blohmer, J; Mousseau, M; Schröder, W; Meier, W; Möbus, V; Richter, B

    2001-01-01

    Since the publication of the Gynecologic Oncology Group (GOG) protocol 111 in 1996, and the results of the Arbeitgemeinschaft Gyna kologische Onkologie (AGO) trial Ovar-3 and the GOG protocol 158, the combination of platinum and paclitaxel has been adopted as the standard therapy in advanced ovarian cancer. One option for achieving further progress in the first-line treatment of advanced ovarian cancer might be the addition of noncross-resistant drugs to the two-drug regimen. Meta-analysis showed a survival benefit for platinum-anthracycline based combinations as compared to platinum-based combinations without anthracyclines. An AGO phase I/II trial compared epirubicin in combination with carboplatin and paclitaxel in untreated patients with gynecological malignancies. Based on the results of this study a randomized phase III trial together with the French GINECO group was conducted. The trial started 11/97 and was closed 11/99. All 1281 patients were randomized. Currently, 1132 end-of-therapy reports have been issued. Nine hundred eighty nine (87%) patients completed six cycles of treatment. Treatment and toxicity data are available for these patients. Three hundred thirty five patients had a measurable residual tumor after initial debulking surgery. Response data of 228 patients (111 ET-Carbo, 117 Carbo-T) are available.

  2. Emerging integrated nanohybrid drug delivery systems to facilitate the intravenous-to-oral switch in cancer chemotherapy.

    Science.gov (United States)

    Luo, Cong; Sun, Jin; Du, Yuqian; He, Zhonggui

    2014-02-28

    Nanohybrid drug delivery systems have presented lots of characteristic advantages as an efficient strategy to facilitate oral drug delivery. Nonetheless, oral administration of chemotherapy agents by nanoparticulate delivery technology still faces great challenges owing to the multiple biobarriers ranging from poorly physicochemical properties of drugs, to complex gastrointestinal disposition and to presystemic metabolism. This review briefly analyzes a series of biobarriers hindering oral absorption and describes the multiple aspects for facilitating the intravenous-to-oral switch in cancer therapy. Moreover, the developed nanoparticulate drug delivery strategies to overcome the above obstacles are provided, including metabolic enzyme inhibition, enteric-coated nanocarriers, bioadhesive and mucus-penetrating strategies, P-gp inhibition and active targeting. On these foundations, the emerging trends of integrated hybrid nanosystems in response to the present low-efficiency drug delivery of any single approach are summarized, such as mixed polymeric micelles and nanocomposite particulate systems. Finally, the recent advances of high-efficiency hybrid nanoparticles in oral chemotherapy are highlighted, with special attention on integrated approach to design drug delivery nanosystems.

  3. Integration of Early Specialist Palliative Care in Cancer Care and Patient Related Outcomes: A Critical Review of Evidence

    Science.gov (United States)

    Salins, Naveen; Ramanjulu, Raghavendra; Patra, Lipika; Deodhar, Jayita; Muckaden, Mary Ann

    2016-01-01

    Introduction: World Health Organization and American Society of Clinical Oncology recommend early integration of specialist palliative care in patients with cancer. This paper focuses on critical review of evidence on integration of early specialist palliative care in cancer care and patient-related outcomes. Methods: The question for the literature search was – Does integration of early specialist palliative care in cancer care influences patient-related outcomes? 31 articles related to literature search review question were included in this paper. Results: Ten patient-related outcomes of early specialist palliative care in adult cancer care was studied. Studies by Temel et al. (2012), Bakitas et al. (2009), Zimmermann et al. (2014), Rugno et al. (2014), Lowery et al. (2013) and Walker et al. (2014) showed early specialist palliative care improves health-related quality of life (HRQOL). Studies by Pirl et al. (2012), Lowery et al. (2013), and Walker et al. (2014) showed early specialist palliative care improved mood depression and anxiety. Studies by Zimmermann et al. and Rugno et al. (2014) showed symptom control benefit of early specialist palliative care. Studies by Temel (2010), Bakitas (2015) and Rugno et al. (2014) showed survival improvement with early specialist palliative care. All these studies were carried in ambulatory palliative care setting. No survival benefit of palliative care intervention was seen in inpatient palliative care setting. The studies by Geer et al. (2012), Rugno et al. (2014), and Lowery et al. (2013) showed that early palliative care intervention positively influences treatment decision making. All the studies showed that palliative care intervention group received less intravenous chemotherapy in last few weeks of life. Studies by Yoong et al. and Temel et al. (2011) shows early specialist palliative care improves advanced care planning. Studies by Temel et al. (2010), Greer et al. (2012), McNamara et al. (2013), Hui et al. (2014

  4. Integration Analysis of Three Omics Data Using Penalized Regression Methods: An Application to Bladder Cancer.

    Science.gov (United States)

    Pineda, Silvia; Real, Francisco X; Kogevinas, Manolis; Carrato, Alfredo; Chanock, Stephen J; Malats, Núria; Van Steen, Kristel

    2015-12-01

    Omics data integration is becoming necessary to investigate the genomic mechanisms involved in complex diseases. During the integration process, many challenges arise such as data heterogeneity, the smaller number of individuals in comparison to the number of parameters, multicollinearity, and interpretation and validation of results due to their complexity and lack of knowledge about biological processes. To overcome some of these issues, innovative statistical approaches are being developed. In this work, we propose a permutation-based method to concomitantly assess significance and correct by multiple testing with the MaxT algorithm. This was applied with penalized regression methods (LASSO and ENET) when exploring relationships between common genetic variants, DNA methylation and gene expression measured in bladder tumor samples. The overall analysis flow consisted of three steps: (1) SNPs/CpGs were selected per each gene probe within 1Mb window upstream and downstream the gene; (2) LASSO and ENET were applied to assess the association between each expression probe and the selected SNPs/CpGs in three multivariable models (SNP, CPG, and Global models, the latter integrating SNPs and CPGs); and (3) the significance of each model was assessed using the permutation-based MaxT method. We identified 48 genes whose expression levels were significantly associated with both SNPs and CPGs. Importantly, 36 (75%) of them were replicated in an independent data set (TCGA) and the performance of the proposed method was checked with a simulation study. We further support our results with a biological interpretation based on an enrichment analysis. The approach we propose allows reducing computational time and is flexible and easy to implement when analyzing several types of omics data. Our results highlight the importance of integrating omics data by applying appropriate statistical strategies to discover new insights into the complex genetic mechanisms involved in disease

  5. Model Uncertainty via the Integration of Hormesis and LNT as the Default in Cancer Risk Assessment

    Directory of Open Access Journals (Sweden)

    Edward J. Calabrese

    2015-12-01

    Full Text Available On June 23, 2015, the US Nuclear Regulatory Commission (NRC issued a formal notice in the Federal Register that it would consider whether “it should amend its ‘Standards for Protection Against Radiation’ regulations from the linear non-threshold (LNT model of radiation protection to the hormesis model.” The present commentary supports this recommendation based on the (1 flawed and deceptive history of the adoption of LNT by the US National Academy of Sciences (NAS in 1956; (2 the documented capacity of hormesis to make more accurate predictions of biological responses for diverse biological end points in the low-dose zone; (3 the occurrence of extensive hormetic data from the peer-reviewed biomedical literature that revealed hormetic responses are highly generalizable, being independent of biological model, end point measured, inducing agent, level of biological organization, and mechanism; and (4 the integration of hormesis and LNT models via a model uncertainty methodology that optimizes public health responses at 10−4. Thus, both LNT and hormesis can be integratively used for risk assessment purposes, and this integration defines the so-called “regulatory sweet spot.”

  6. Integration of estrogen and progesterone receptors with pathological and molecular prognostic factors in breast cancer patients.

    Science.gov (United States)

    Gago, F E; Tello, O M; Diblasi, A M; Ciocca, D R

    1998-12-01

    In this study we have examined biopsies from women with localized primary breast cancer to investigate the prognostic performance of estrogen receptors (ER) and progesterone receptors (PR) for estimating the metastatic probability of the patients, and to explore whether discrimination gets better by combining clinicopathological and other molecular parameters into a score. This prospective study involved 205 patients with a median follow-up of 5 y. Among the evaluated clinicopathological data were: patient's age; tumor size; axillary lymph node involvement; and tumor grade. The most representative tumor samples were derived to a single laboratory for immunohistochemical evaluation of the following molecular markers: ER, PR, proliferating cell nuclear antigen (PCNA), p53 protein product, erbB-2 (HER-2/neu) oncoprotein, and P170 glycoprotein (mdrl gen product). Distant metastases (study endpoint) appeared in 19.5% (40/205) of the patients, most of these patients presented a mixture of poor, regular and good prognostic factors. Disease-free survival analysis procedures (Kaplan-Meier method) identified tumor size, axillary lymph node involvement, tumor grade, receptor status, PCNA, p53, erbB-2 and P170 as useful prognostic factors. Proportional hazard regression analysis (Cox) identified in order of importance erbB-2, tumor size, receptors status, tumor grade and PCNA as useful prognostic factors. To facilitate the evaluation of the prognostic factors, a practical and simple score system was derived. A high pathological score identified 65% of the patients that developed distant metastases, while a high molecular score was obtained in 57% of patients with metastatic disease. There was a significant improvement in the diagnosis of probability of being with distant metastases when the pathological score was combined with the molecular score, 82% of the patients with distant metastases showed an elevated combined score. Validation of this scoring system will need further

  7. Supervised multi-view canonical correlation analysis (sMVCCA): integrating histologic and proteomic features for predicting recurrent prostate cancer.

    Science.gov (United States)

    Lee, George; Singanamalli, Asha; Wang, Haibo; Feldman, Michael D; Master, Stephen R; Shih, Natalie N C; Spangler, Elaine; Rebbeck, Timothy; Tomaszewski, John E; Madabhushi, Anant

    2015-01-01

    In this work, we present a new methodology to facilitate prediction of recurrent prostate cancer (CaP) following radical prostatectomy (RP) via the integration of quantitative image features and protein expression in the excised prostate. Creating a fused predictor from high-dimensional data streams is challenging because the classifier must 1) account for the "curse of dimensionality" problem, which hinders classifier performance when the number of features exceeds the number of patient studies and 2) balance potential mismatches in the number of features across different channels to avoid classifier bias towards channels with more features. Our new data integration methodology, supervised Multi-view Canonical Correlation Analysis (sMVCCA), aims to integrate infinite views of highdimensional data to provide more amenable data representations for disease classification. Additionally, we demonstrate sMVCCA using Spearman's rank correlation which, unlike Pearson's correlation, can account for nonlinear correlations and outliers. Forty CaP patients with pathological Gleason scores 6-8 were considered for this study. 21 of these men revealed biochemical recurrence (BCR) following RP, while 19 did not. For each patient, 189 quantitative histomorphometric attributes and 650 protein expression levels were extracted from the primary tumor nodule. The fused histomorphometric/proteomic representation via sMVCCA combined with a random forest classifier predicted BCR with a mean AUC of 0.74 and a maximum AUC of 0.9286. We found sMVCCA to perform statistically significantly (p state-of-the-art data fusion strategies for predicting BCR. Furthermore, Kaplan-Meier analysis demonstrated improved BCR-free survival prediction for the sMVCCA-fused classifier as compared to histology or proteomic features alone.

  8. Study of integrated heterogeneous data reveals prognostic power of gene expression for breast cancer survival.

    Directory of Open Access Journals (Sweden)

    Richard E Neapolitan

    Full Text Available Studies show that thousands of genes are associated with prognosis of breast cancer. Towards utilizing available genetic data, efforts have been made to predict outcomes using gene expression data, and a number of commercial products have been developed. These products have the following shortcomings: 1 They use the Cox model for prediction. However, the RSF model has been shown to significantly outperform the Cox model. 2 Testing was not done to see if a complete set of clinical predictors could predict as well as the gene expression signatures.We address these shortcomings. The METABRIC data set concerns 1981 breast cancer tumors. Features include 21 clinical features, expression levels for 16,384 genes, and survival. We compare the survival prediction performance of the Cox model and the RSF model using the clinical data and the gene expression data to their performance using only the clinical data. We obtain significantly better results when we used both clinical data and gene expression data for 5 year, 10 year, and 15 year survival prediction. When we replace the gene expression data by PAM50 subtype, our results are significant only for 5 year and 15 year prediction. We obtain significantly better results using the RSF model over the Cox model. Finally, our results indicate that gene expression data alone may predict long-term survival.Our results indicate that we can obtain improved survival prediction using clinical data and gene expression data compared to prediction using only clinical data. We further conclude that we can obtain improved survival prediction using the RSF model instead of the Cox model. These results are significant because by incorporating more gene expression data with clinical features and using the RSF model, we could develop decision support systems that better utilize heterogeneous information to improve outcome prediction and decision making.

  9. Short Review

    DEFF Research Database (Denmark)

    Lynnerup, Niels; Rühli, Frank

    2015-01-01

    modality in ancient mummy research. The aim of this short review is to address the advantages and pitfalls of this particular technique for such unique samples. We recommend that when results of X-ray examination of mummies are presented, the specific recording data should be listed, and any given finds......, for example, of Paleopathology, should be cross-checked against other sources, for example, CT-scanning, direct inspection (also by endoscopy), and so forth....

  10. Cake: a bioinformatics pipeline for the integrated analysis of somatic variants in cancer genomes

    Science.gov (United States)

    Rashid, Mamunur; Robles-Espinoza, Carla Daniela; Rust, Alistair G.; Adams, David J.

    2013-01-01

    Summary: We have developed Cake, a bioinformatics software pipeline that integrates four publicly available somatic variant-calling algorithms to identify single nucleotide variants with higher sensitivity and accuracy than any one algorithm alone. Cake can be run on a high-performance computer cluster or used as a stand-alone application. Availabilty: Cake is open-source and is available from http://cakesomatic.sourceforge.net/ Contact: da1@sanger.ac.uk Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:23803469

  11. Cancer

    Science.gov (United States)

    ... uses a surgical tool to remove the tumor.Mohs' surgery. Layers of cancer cells are removed one ... usually have not been approved by the U.S. Food and Drug Administration (FDA). The medicine may have ...

  12. A Subacute Care Intervention for Short-Stay Breast Cancer Surgery Self-Test Kit: Rapid Diagnosis of Urogenital Infections in Military Women

    Science.gov (United States)

    1998-10-01

    Costs in Studies of Treatment Effectiveness", " Music and Healing for Women with Breast Cancer", and "Impaired Cognition in Cancer Patients." All... Effetive and completed 3. Single time intervention, cg,, cachln& llteratur, demo 3. Intervention effective, Dx resolved 4. Non-compliant 4. After initial use...pattern El hs snack El loose clothing El massage El music El positioning El tepid bath El warm liquids El unknown Cause (choose only 2): 0 anxiety El

  13. An integrated analysis of genes and pathways exhibiting metabolic differences between estrogen receptor positive breast cancer cells

    Directory of Open Access Journals (Sweden)

    Davie James R

    2007-09-01

    Full Text Available Abstract Background The sex hormone estrogen (E2 is pivotal to normal mammary gland growth and differentiation and in breast carcinogenesis. In this in silico study, we examined metabolic differences between ER(+ve breast cancer cells during E2 deprivation. Methods Public repositories of SAGE and MA gene expression data generated from E2 deprived ER(+ve breast cancer cell lines, MCF-7 and ZR75-1 were compared with normal breast tissue. We analyzed gene ontology (GO, enrichment, clustering, chromosome localization, and pathway profiles and performed multiple comparisons with cell lines and tumors with different ER status. Results In all GO terms, biological process (BP, molecular function (MF, and cellular component (CC, MCF-7 had higher gene utilization than ZR75-1. Various analyses showed a down-regulated immune function, an up-regulated protein (ZR75-1 and glucose metabolism (MCF-7. A greater percentage of 77 common genes localized to the q arm of all chromosomes, but in ZR75-1 chromosomes 11, 16, and 19 harbored more overexpressed genes. Despite differences in gene utilization (electron transport, proteasome, glycolysis/gluconeogenesis and expression (ribosome in both cells, there was an overall similarity of ZR75-1 with ER(-ve cell lines and ER(+ve/ER(-ve breast tumors. Conclusion This study demonstrates integral metabolic differences may exist within the same cell subtype (luminal A in representative ER(+ve cell line models. Selectivity of gene and pathway usage for strategies such as energy requirement minimization, sugar utilization by ZR75-1 contrasted with MCF-7 cells, expressing genes whose protein products require ATP utilization. Such characteristics may impart aggressiveness to ZR75-1 and may be prognostic determinants of ER(+ve breast tumors.

  14. Challenges in integrating 18FDG PET-CT into radiotherapy planning of head and neck cancer.

    Science.gov (United States)

    Dandekar, P; Partridge, M; Kazi, R; Nutting, C; Harrington, K; Newbold, K

    2010-01-01

    Radiotherapy forms one of the major treatment modalities for head and neck cancers (HNC), and precision radiotherapy techniques, such as intensity-modulated radiotherapy require accurate target delineation to ensure success of the treatment. Conventionally used imaging modalities, such as X-ray computed tomography (CT) and magnetic resonance imaging are used to delineate the tumor. Imaging, such as positron emission tomography (PET)-CT, which combines the functional and anatomic modalities, is increasingly being used in the management of HNC. Currently, 18-fluorodeoxyglucose is the most commonly used radioisotope, which is accumulated in areas of high glucose uptake, such as the tumor tissue. Because most disease recurrences are within the high-dose radiotherapy volume, defining a biological target volume for radiotherapy boost is an attractive approach to improve the results. There are many challenges in employing the PET-CT for radiotherapy planning, such as patient positioning, target edge definition, and use of new PET tracers, which represent various functional properties, such as hypoxia, protein synthesis, and proliferation. The role of PET-CT for radiotherapy planning is ever expanding and more clinical data underlining the advantages and challenges in this approach are emerging. In this article, we review the current clinical evidence for the application of functional imaging to radiotherapy planning and discuss some of the current challenges and possible solutions that have been suggested to date.

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

    Directory of Open Access Journals (Sweden)

    Nam Seungyoon

    2012-12-01

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

  16. Short communication. Evaluation of a commercial kit based on acridine orange/propidium iodide to assess the plasma membrane integrity of ram sperm

    Directory of Open Access Journals (Sweden)

    J. L. Yániz

    2013-03-01

    Full Text Available This study was designed to develop a semiautomatic computer assisted methodology to evaluate the membrane integrity of ram spermatozoa using a commercial kit based on acridine orange/propidium iodide (AO/PI labelling and ImageJ software. The study was divided into two experiments. In the first trial, the new computer-assisted method was validated by mixing fresh semen samples with different volumes of freeze killed spermatozoa to determine proportions of damaged spermatozoa in the final samples. The proportion of damaged spermatozoa in each sample determined by the automated procedure where highly correlated (R2=0.97, p<0.001 with the predicted theoretical values. In the second trial, the new method was compared with a previously validated method of membrane integrity assessment based on phase-contrast/propidium iodide (PH/PI methodology. Measurements by AO/PI were, on average, 4.0% larger than measurements by PH/PI (SD=7.02% and 1.79% smaller than measurements of sperm motility determined by CASA (SD=4.83. The AO/PI method was also more repeatable than the PH/PI. The double staining methodology coupled with the routine for image analysis allowing automatic determination of sperm membrane integrity means a reduction in processing time of 75% compared to the previously developed method using a single fluorochrome (3 vs 12 min on average if the incubation period was included. This facilitates its use when a large number of samples are analysed. Our results validate the new computer assisted method for assessing sperm membrane integrity in sheep. The new method developed, in addition to being a free tool, allows quick automatic determination of sperm viability, which facilitates its use in routine semen analysis.

  17. 肿瘤患者的短期团体认知行为干预%Short-term group cognitive behavioral intervention in cancer patients

    Institute of Scientific and Technical Information of China (English)

    郑儒君; 符琰; 陈林; 牟倩倩; 刘珊珊; 李俊英; 余春华

    2015-01-01

    .7) points (t=11.8, P<0.05), and the proportions of distress problems contained anxiety [42.2% (27/64)], pain [29.7% (19/64)], depression [35.9% (23/64)] and sleep [23.4% (15/64)] in the experimental group were all significant lower than the control group [60.6% (40/66), 47.0% (31/66), 53.0% (35/66), 39.4% (26/66)]( X2=4.4, 4.1, 3.9, 4.5, P<0.05). Conclusions Short-term group cognitive behavioral intervention can alleviate the distress and pain, improve their negative emotions and sleep, eventually improve the quality of life of cancer patients.