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  1. Genetics Home Reference: prostate cancer

    MedlinePlus

    ... Email Facebook Twitter Home Health Conditions prostate cancer prostate cancer Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Prostate cancer is a common disease that affects men, usually ...

  2. Genetics Home Reference: lung cancer

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions lung cancer lung cancer Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Lung cancer is a disease in which certain cells ...

  3. Development of the Home Learning Environment Profile.

    ERIC Educational Resources Information Center

    Heath, Robert W.; And Others

    The development and validation of the Home Learning Environment Profile (HLEP) are outlined. The HLEP instrument was designed to assess successful preschool home educational programs for Hawaiian families. The instrument covers sociodemographic, cultural, and environmental factors of Hawaiian families. After an extensive review of published…

  4. Development of the Home Learning Environment Profile.

    ERIC Educational Resources Information Center

    Heath, Robert W.; And Others

    The development and validation of the Home Learning Environment Profile (HLEP) are outlined. The HLEP instrument was designed to assess successful preschool home educational programs for Hawaiian families. The instrument covers sociodemographic, cultural, and environmental factors of Hawaiian families. After an extensive review of published…

  5. Occupational Competency Profiles for Vocational Home Economics.

    ERIC Educational Resources Information Center

    Texas Education Agency, Austin.

    This package consists of occupational competency profiles for evaluation of students in vocational home economics courses in Texas. The package begins with a rating sheet of essential elements for all vocational programs, with space for instructors to rate students on a four-point scale, followed by a competency profile sheet. Competency…

  6. Profiles in Cancer Research

    Cancer.gov

    These articles put a face to some of the thousands of individuals who contribute to NCI’s cancer research efforts. The profiles highlight the work of scientists and clinicians and describe the circumstances and motivation behind their work.

  7. Genetics Home Reference: hereditary diffuse gastric cancer

    MedlinePlus

    ... Twitter Home Health Conditions hereditary diffuse gastric cancer hereditary diffuse gastric cancer Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Hereditary diffuse gastric cancer (HDGC) is an inherited disorder ...

  8. Genetics Home Reference: breast cancer

    MedlinePlus

    ... cancers . A small percentage of all breast cancers cluster in families. These cancers are described as hereditary ... will develop breast cancer . Some breast cancers that cluster in families are associated with inherited mutations in ...

  9. Homing of cancer cells to the bone.

    PubMed

    Mishra, Anjali; Shiozawa, Yusuke; Pienta, Kenneth J; Taichman, Russell S

    2011-12-01

    A variety of tumor cells preferentially home to the bone. The homing of cancer cells to the bone represents a multi-step process that involves malignant progression of the tumor, invasion of the tumor through the extracellular matrix and the blood vessels and settling of the tumor cells in the bone. Gaining a greater understanding as to the mechanisms used by cancer cells in these processes will facilitate the design of drugs which could specifically target the homing process. In this review we will discuss the properties of tumor cells and the bone microenvironment which promote homing of a cancer cell to the bone. We will highlight the different steps and the molecular pathways involved when a cancer cell metastasize to the bone. Since bone is the major home for hematopoietic stem cells (HSCs), we will also highlight the similarities between the homing of cancer and HSC to the bone. Finally we will conclude with therapeutic and early detection strategies which can prevent homing of a cancer cell to the bone.

  10. Home Care Nursing Improves Cancer Symptom Management

    Cancer.gov

    Home care nursing (HCN) improves the management of symptoms in breast and colorectal cancer patients who take the oral chemotherapy drug capecitabine, according to a study published online November 16 in the Journal of Clinical Oncology.

  11. Genetics Home Reference: ovarian cancer

    MedlinePlus

    ... body are called metastatic cancers. Some ovarian cancers cluster in families. These cancers are described as hereditary ... during a person's lifetime, and they do not cluster in families. A predisposition to cancer caused by ...

  12. Home | Division of Cancer Prevention

    Cancer.gov

    Our Research The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into cancer. |

  13. Home care workers. A national profile.

    PubMed

    Crown, W; MacAdam, M; Sadowsky, E

    1992-04-01

    This study presents the first nationally representative estimates of the characteristics of home care aides compared with nursing aides and hospital aides. For nearly every characteristic examined, substantial differences among the three types of aides exist. Understanding the distinct characteristics and needs of the home care aide is the first step toward increasing job satisfaction and reducing para-professional turnover.

  14. Home | Cancer Trends Progress Report

    Cancer.gov

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  15. Genetics Home Reference: parathyroid cancer

    MedlinePlus

    ... fifties and occurs in one of the four parathyroid glands . The parathyroid glands are located in the neck and secrete parathyroid ... cancer is described as hormonally functional because the parathyroid glands are producing excess hormone. Many individuals with hormonally ...

  16. Genetics Home Reference: bladder cancer

    MedlinePlus

    ... Kozlowski JM. The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the ... Zwarthoff EC, Radvanyi F. Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified ...

  17. "The home infusion patient": patient profiles for the home infusion therapy market.

    PubMed

    Westbrook, K W; Powers, T

    1999-01-01

    The authors review the relevant literature regarding home health care patient profiles. An empirical analysis is provided from archival data for a home infusion company servicing patients in urban and rural areas. The results are provided as a 2 x 2 matrix for patients in urban and rural areas seeing either a specialist or primary care physicians. A series of moderated regressions indicate that type of treating physician, patient's gender, geographic residence and level of acuity are cogent in predicting the complexity of prescribed infusion therapies. Managerial implications are provided for the home care marketer in segmenting patient markets for infusion services.

  18. Spanish Developmental Dyslexia: Prevalence, Cognitive Profile, and Home Literacy Experiences

    ERIC Educational Resources Information Center

    Jimenez, Juan E.; Rodriguez, Cristina; Ramirez, Gustavo

    2009-01-01

    This study was designed to examine the prevalence, cognitive profile, and home literacy experiences in subtypes of Spanish developmental dyslexia. The subtyping procedure used comparison with chronological-age-matched and reading-level controls on reaction times and accuracy responses to high-frequency words and pseudowords. Using regression-based…

  19. Genomic profiling of breast cancers.

    PubMed

    Curtis, Christina

    2015-02-01

    To describe recent advances in the application of advanced genomic technologies towards the identification of biomarkers of prognosis and treatment response in breast cancer. Advances in high-throughput genomic profiling such as massively parallel sequencing have enabled researchers to catalogue the spectrum of somatic alterations in breast cancers. These tools also hold promise for precision medicine through accurate patient prognostication, stratification, and the dynamic monitoring of treatment response. For example, recent efforts have defined robust molecular subgroups of breast cancer and novel subtype-specific oncogenes. In addition, previously unappreciated activating mutations in human epidermal growth factor receptor 2 have been reported, suggesting new therapeutic opportunities. Genomic profiling of cell-free tumor DNA and circulating tumor cells has been used to monitor disease burden and the emergence of resistance, and such 'liquid biopsy' approaches may facilitate the early, noninvasive detection of aggressive disease. Finally, single-cell genomics is coming of age and will contribute to an understanding of breast cancer evolutionary dynamics. Here, we highlight recent studies that employ high-throughput genomic technologies in an effort to elucidate breast cancer biology, discover new therapeutic targets, improve prognostication and stratification, and discuss the implications for precision cancer medicine.

  20. Day Care Homes: A Pennsylvania Profile. Center for Human Services Development Report No. 18.

    ERIC Educational Resources Information Center

    Peters, Donald L.

    This report presents a preliminary profile of home day care in Pennsylvania. Information was gathered through extensive questionnaires and home observations which occurred during site visits to a geographically-representative sample of 162 licensed or approved day care homes. In the profile, comparisons are made between 146 homes which are…

  1. Proteomic profiling of cancer biomarkers.

    PubMed

    Shau, Hungyi; Chandler, G Scott; Whitelegge, Julian P; Gornbein, Jeffrey A; Faull, Kym F; Chang, Helena R

    2003-07-01

    Early detection and correct diagnosis are essential for effective treatment of cancer and patient survival. Complete sequencing of the human genome, and the genomes of other species, provides valuable tools for discerning the genetic abnormalities in cancer. However, differences between cancerous and normal cells reflect more than variations in genetic sequences and abundance of transcribed RNA. Many cancer biomarkers are manifestation of differences in post-transcriptional splicing and/or post-translational modifications. Thus, proteomic tools are being increasingly utilised in the post-genomic era for discovery of new cancer biomarkers. In this paper we will provide an overview of the biomarker discovery process from the proteomic profiling point of view, with emphasis given to the principles that are involved in the process, including the protein identification strategies, and how surface enhanced laser desorption ionisation mass spectrometry fits into the picture. The aim is to provide a resource for the experimental practitioner seeking awareness of the analytical tools that are now available in contemporary cancer research.

  2. Spanish developmental dyslexia: prevalence, cognitive profile, and home literacy experiences.

    PubMed

    Jiménez, Juan E; Rodríguez, Cristina; Ramírez, Gustavo

    2009-06-01

    This study was designed to examine the prevalence, cognitive profile, and home literacy experiences in subtypes of Spanish developmental dyslexia. The subtyping procedure used comparison with chronological-age-matched and reading-level controls on reaction times and accuracy responses to high-frequency words and pseudowords. Using regression-based procedures, 8 phonological dyslexics and 16 surface dyslexics were identified from a sample of 35 dyslexic fourth graders by comparing them with chronological-age-matched controls on reaction times to high-frequency word and pseudoword reading. However, when the dyslexic subtypes were defined by reference to reading-level controls, 12 phonological dyslexics were defined but only 5 surface dyslexics were identified. Both dyslexic subtypes showed a deficit in phonological awareness, but children with surface dyslexia also showed a deficit in orthographical processing assessed by a homophone comprehension task. This deficit was associated with poor home literacy experiences, with the group of parents with children matched in reading age, in comparison with the group of parents with children with surface dyslexia, reporting more literacy home experiences.

  3. The 24-h recall instrument for home nursing to measure the activity profile of home nurses: development and psychometric testing.

    PubMed

    De Vliegher, Kristel; Aertgeerts, Bert; Declercq, Anja; Gosset, Christiane; Heyden, Isabelle; Van Geert, Michel; Moons, Philip

    2015-01-01

    Home health care today is challenged by a shift from an acute to a chronic health-care model, moving the focus of care from the hospital to home-care setting. This increased focus on care at home emphasizes the need for an efficient, effective, and transparent management of home health care. However, it is not precisely known what home-care nurses do; what kind of care is received by patients; what the performance of home nurses is; and what the impact of the increasing need for home nursing is on the current and future role of home nurses. In this respect, it is necessary to gain a clear insight into the activity profile of home nurses, but there is no gold standard to measure their activities. This study reports on the development and psychometric testing of the '24-hour recall instrument for home nursing' to measure the activity profile of home nurses. Five home nurses in Belgium, simultaneously with the researcher, registered the performed activities in a total of 69 patients, using the 24-h recall instrument for home nursing. The validity and the interrater reliability of this instrument were high: the proportions that observed agreement were very high; the strength of kappa agreement was substantial to almost perfect; the prevalence index showed great variety; and the bias index was low. The findings in this study support the validity evidence based on test content and the interrater reliability of the 24-h recall instrument. This instrument can help to shape practice and policy by making the home nursing profession more transparent: a clear insight into the kind of care that is provided by home nurses and is received by the patients in primary care contributes to the development of a clear definition of the role of home nurses in health care.

  4. A Confirmatory Factor Analysis of Home Environment and Home Social Behavior Data from the Elementary School Success Profile for Families

    ERIC Educational Resources Information Center

    Wegmann, Kate M.; Thompson, Aaron M.; Bowen, Natasha K.

    2011-01-01

    The purpose of the current study was to test the factor structure and scale quality of data provided by caregivers about the home environment and child behavior at home using the Elementary School Success Profile (ESSP) for Families. The ESSP for Families is one component of the ESSP, an online social-environmental assessment that also collects…

  5. A Confirmatory Factor Analysis of Home Environment and Home Social Behavior Data from the Elementary School Success Profile for Families

    ERIC Educational Resources Information Center

    Wegmann, Kate M.; Thompson, Aaron M.; Bowen, Natasha K.

    2011-01-01

    The purpose of the current study was to test the factor structure and scale quality of data provided by caregivers about the home environment and child behavior at home using the Elementary School Success Profile (ESSP) for Families. The ESSP for Families is one component of the ESSP, an online social-environmental assessment that also collects…

  6. MicroRNA profiling in cancer.

    PubMed

    Munker, Reinhold; Calin, George A

    2011-08-01

    The diagnosis of cancer has undergone major changes in the last 40 years. Once based purely on morphology, diagnosis has come to incorporate immunological, cytogenetic and molecular methods. Many cancers, especially leukaemias, are now defined by molecular markers. Gene expression profiling based on mRNA has led to further refinement of the classification and diagnosis of cancer. More recently, miRNAs (microRNAs), among other small non-coding RNA molecules, have been discovered and found to be major players in cell biology. miRNAs, having both oncogenic and tumour-suppressive functions, are dysregulated in many types of cancer. miRNAs also interfere with metastasis, apoptosis and invasiveness of cancer cells. In the present review, we discuss recent advances in miRNA profiling in human cancer. We discuss both frequent and rare tumour types and give an outlook on future developments.

  7. Integrated Molecular Profiling in Advanced Cancers Trial

    ClinicalTrials.gov

    2016-08-19

    Breast Cancer; Non-small Cell Lung Cancer; Colorectal Cancer; Genitourinary Cancer; Pancreatobiliary Gastrointestinal Cancer; Upper Aerodigestive Tract Cancer; Gynecological Cancers; Melanoma Cancers; Rare Cancers; Unknown Primary Cancers

  8. Translating genomic profiling to gastrointestinal cancer treatment.

    PubMed

    Harada, Kazuto; Mizrak Kaya, Dilsa; Shimodaira, Yusuke; Song, Shumei; Baba, Hideo; Ajani, Jaffer A

    2017-04-01

    Next-generation sequencing enables faster, cheaper and more accurate whole-genome sequencing, allowing genome profiling and discovery of molecular features. As molecular targeted drugs are developed, treatment can be tailored according to molecular subtype. Gastric and colorectal cancers have each been divided into four subtypes according to molecular features. Profiling of the esophageal cancer genome is underway and its classification is anticipated. To date, identification of HER2 expression in gastric adenocarcinoma and KRAS, NRAS and BRAF mutations in colon cancer have proved essential for treatment decisions. However, to overcome therapy resistance and improve prognosis, further individualized therapy is required. Here, we summarize the treatment options for gastrointestinal cancer according to genomic profiling and discuss future directions.

  9. Profile of childhood cancers: a multicentric study.

    PubMed

    Roy, Birendra Nath; Purkait, Radheshyam; Ganguly, Subir; Samanta, Tryambak; Gayen, Shibnath; Pal, Sumita

    2012-12-01

    The incidence of cancer has been increasing steadily in the developing world including India. Childhood cancers are a special entity with different genetic, environmental factors playing a role in their aetiology. The profiles of cancer incidence reflect the racial, cultural and geographical diversity within populations. This article shows the profile of childhood cancer across three medical college hospitals in the state of West Bengal in India and the data were collected from the period between 2008 and 2011. The results showed leukaemia was the most common cancer affecting children followed by lymphoma and retinoblastoma.The profile of childhood cancers showed wide variation among the age groups. Frequency of retinoblastoma, renal tumours, neuroblastoma and hepatic tumours were higher in children less than five years whereas lymphoma, leukaemia, bone tumours and central nervous system tumours were found more in children above five years. As many of common childhood malignancies are curable there is need to have a dedicated paediatric cancer registry for assessing the magnitude of problem in our country as paediatric cancers show wide variation across centres.

  10. ICPS: an integrative cancer profiler system.

    PubMed

    Zhang, Xin-yu; Shi, Lin; Liu, Yan; Tian, Feng; Zhao, Hai-tao; Miao, Xiao-ping; Huang, Ming-lie; Zhu, Xiao-yan

    2010-10-15

    Founded upon the database of 570 public signatures, ICPS is a web-based application to obtain biomarker profiles among 11 common cancers by integrating genomic alterations with transcription signatures on the basis of a previously developed integrative pipeline. ICPS supports both public data and user's in-house data, and performs meta-analysis at a cancer subtype level by combining heterogeneous datasets. Finally, ICPS returns the robust gene signature containing potential cancer biomarkers that may be useful to carcinogenesis study and clinical cancer diagnosis. http://server.bioicps.org zhxy@mail.tsinghua.edu.cn; zxy-dcs@mail.tsinghua.edu.cn

  11. Promoting cancer screening within the patient centered medical home.

    PubMed

    Sarfaty, Mona; Wender, Richard; Smith, Robert

    2011-01-01

    While consensus has grown that primary care is the essential access point in a high-performing health care system, the current model of primary care underperforms in both chronic disease management and prevention. The Patient Centered Medical Home model (PCMH) is at the center of efforts to reinvent primary care practice, and is regarded as the most promising approach to addressing the burden of chronic disease, improving health outcomes, and reducing health spending. However, the potential for the medical home to improve the delivery of cancer screening (and preventive services in general) has received limited attention in both conceptualization and practice. Medical home demonstrations to date have included few evidence-based preventive services in their outcome measures, and few have evaluated the effect of different payment models. Decreasing use of hospitals and emergency rooms and an emphasis on improving chronic care represent improvements in effective delivery of healthcare, but leave opportunities for reducing the burden of cancer untouched. Data confirm that what does or does not happen in the primary care setting has a substantial impact on cancer outcomes. Insofar as cancer is the leading cause of death before age 80, the PCMH model must prioritize adherence to cancer screening according to recommended guidelines, and systems, financial incentives, and reimbursements must be aligned to achieve that goal. This article explores capacities that are needed in the medical home model to facilitate the integration of cancer screening and other preventive services. These capacities include improved patient access and communication, health risk assessments, periodic preventive health exams, use of registries that store cancer risk information and screening history, ability to track and follow up on tests and referrals, feedback on performance, and payment models that reward cancer screening.

  12. Gene-expression profiling in pancreatic cancer.

    PubMed

    López-Casas, Pedro P; López-Fernández, Luís A

    2010-07-01

    Pancreatic cancer has one of the worst prognoses, owing principally to a late diagnosis and the absence of good treatments. In the last 5 years, up to 12 molecular pathways involved in pancreatic cancer have been described. Global gene-expression profiling and the use of microarray databases have allowed the identification of hundreds of genes that are differentially expressed in pancreatic cancer. However, validation of these genes as biomarkers for early diagnosis, prognosis or treatment efficacy is still incomplete. Additionally, microRNAs have emerged as a potential source of variation between cancer and normal samples, and several of them have been identified as being deregulated in pancreatic tumors. An integrative point of view in the study of pancreatic cancer that makes use of all the whole-genome technologies has revealed several molecular mechanisms that affect pancreatic cancer development. These results should encourage the use of more personalized medicine in this pathology. Recent developments and future perspectives are discussed.

  13. Building America Top Innovations 2013 Profile – HPXML: A Standardized Home Performance Data Sharing System

    SciTech Connect

    none,

    2013-09-01

    This Top Innovation profile describes the Standard for Home Performance-Related Data Transfer (known as HPXML), developed by the National Renewable Energy Laboratory, which facilitates smooth communication between program tracking systems and energy upgrade analysis software,

  14. 38 CFR 58.10 - VA Form 10-3567-State Home Inspection Staffing Profile.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2013-07-01 2013-07-01 false VA Form 10-3567-State Home Inspection Staffing Profile. 58.10 Section 58.10 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) FORMS § 58.10 VA Form 10-3567—State Home Inspection Staffing Profile. ER06JA00.000 ER06JA00.001...

  15. 38 CFR 58.10 - VA Form 10-3567-State Home Inspection Staffing Profile.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false VA Form 10-3567-State Home Inspection Staffing Profile. 58.10 Section 58.10 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) FORMS § 58.10 VA Form 10-3567—State Home Inspection Staffing Profile. ER06JA00.000 ER06JA00.001...

  16. 38 CFR 58.10 - VA Form 10-3567-State Home Inspection Staffing Profile.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2012-07-01 2012-07-01 false VA Form 10-3567-State Home Inspection Staffing Profile. 58.10 Section 58.10 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) FORMS § 58.10 VA Form 10-3567—State Home Inspection Staffing Profile. ER06JA00.000 ER06JA00.001...

  17. 38 CFR 58.10 - VA Form 10-3567-State Home Inspection Staffing Profile.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false VA Form 10-3567-State Home Inspection Staffing Profile. 58.10 Section 58.10 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS (CONTINUED) FORMS § 58.10 VA Form 10-3567—State Home Inspection Staffing Profile. ER06JA00.000 ER06JA00.001...

  18. Profiling metabolic networks to study cancer metabolism.

    PubMed

    Hiller, Karsten; Metallo, Christian M

    2013-02-01

    Cancer is a disease of unregulated cell growth and survival, and tumors reprogram biochemical pathways to aid these processes. New capabilities in the computational and bioanalytical characterization of metabolism have now emerged, facilitating the identification of unique metabolic dependencies that arise in specific cancers. By understanding the metabolic phenotype of cancers as a function of their oncogenic profiles, metabolic engineering may be applied to design synthetically lethal therapies for some tumors. This process begins with accurate measurement of metabolic fluxes. Here we review advanced methods of quantifying pathway activity and highlight specific examples where these approaches have uncovered potential opportunities for therapeutic intervention.

  19. [Ways to make cooperation between hospital nurse and home visiting nurse in treating a final stage cancer patient at home].

    PubMed

    Nagai, Hamae; Ohori, Yoko; Shino, Satoko; Marutani, Harumi; Numata, Kumiko; Sato, Yasutomo

    2005-12-01

    Due to a payment system based on Comprehensive Medical Evaluation has been adopted, both a shorter hospitalization and the use of home nursing care have been increasing. A good cooperation between hospital and home visiting nurses is desired in order to transfer continued nursing. Regarding a home nursing care service for the most terminal cancer patients, we conducted a survey of 459 home visiting nurses with twelve questions in five categories: (1) Before transferring to home care, (2) Right after the transfer to home care, (3) Patient in a stable period, (4) Time of near death and (5) Other (Requests to hospital nurses). The following issues became clearer in terms of how hospital and home visiting nurses should be cooperating with the handling of last stage terminal cancer patients: (1) A home visiting nurse should have a coordinating role with a hospital nurse when the patient is discharged from the hospital. (2) A participation of home visiting nurses on the coordination guidance at the time of a patient discharge is influenced by a manpower of the nursing station. (3) Even though home visiting nurses found a discrepancy between the hospital information and what patients and their families were getting from the hospital, home visiting nurses have learned through the job to clarify what patient and family needs were, and they responded accordingly. (4) A coordination between hospital and home visiting nurses was needed quite often when the patient's time has come to die at home.

  20. Functional profiling methods in cancer.

    PubMed

    Dopazo, Joaquín

    2010-01-01

    The introduction of new high-throughput methodologies such as DNA microarrays constitutes a major breakthrough in cancer research. The unprecedented amount of data produced by such technologies has opened new avenues for interrogating living systems although, at the same time, it has demanded of the development of new data analytical methods as well as new strategies for testing hypotheses. A history of early successful applications in cancer boosted the use of microarrays and fostered further applications in other fields. Keeping the pace with these technologies, bioinformatics offers new solutions for data analysis and, what is more important, permits the formulation of a new class of hypotheses inspired in systems biology, more oriented to pathways or, in general, to modules of functionally related genes. Although these analytical methodologies are new, some options are already available and are discussed in this chapter.

  1. Targeting cancer cell invasiveness using homing peptide-nanocomplexes

    NASA Astrophysics Data System (ADS)

    Suarato, Giulia; Cathcart, Jillian; Li, Weiyi; Cao, Jian; Meng, Yizhi

    Matrix metalloproteinase-14 (MMP-14) plays critical roles in digesting the basement membrane and extracellular matrix and inducing cancer migration. We recently unraveled a unique role in cell invasion of the hemopexin (PEX) domain of MMP-14. The minimal motif located at the outmost strand of the fourth blade of the PEX domain was identified to form homodimers of MMP-14. A peptide (IVS4) mimicking the binding motif was shown to interrupt MMP-14 dimerization and decrease MMP-14-mediated functions. Since most invasive cancer cells express upregulated MMP-14 at the surface, IVS4 could be used as a cancer homing peptide to specifically deliver cytotoxic drugs for cancer therapy. We developed cancer homing nanocarriers by linking IVS4 to polysaccharide-based micellar nanoparticles (NPs). To determine if conjugation of IVS4 to NPs maintains the IVS4 inhibition of MMP-14 function, substrate degradation and cell migration assays were performed. IVS4-NPs efficiently prevented MMP-14-mediated substrate degradation and cell migration, and were minimally uptaken by non-cancer cells. Importantly, IVS4 confers an uptake advantage compared to the control peptide in MMP-14-expressing cells. Taken together, our findings demonstrate the potential use of IVS4-NPs as novel cancer nanotherapeutics.

  2. Yearly transitions of disability profiles in older people living at home.

    PubMed

    Raîche, Michel; Hébert, Réjean; Dubois, Marie-France; Gueye, N'deye Rokhaya; Dubuc, Nicole

    2012-01-01

    Planning home services for older people requires extensive knowledge about the progression of disabilities. Disability-based case-mix classifications identify meaningful groups of older people; yet transitions between profiles are mostly unknown. Disability was assessed annually over four years with the Functional Autonomy Measurement System (SMAF) in 1410 older people at risk of functional decline aged 75 and over and living at home. The SMAF generates a case-mix classification of 14 Iso-SMAF profiles with progressive mean disability levels. Transitions made by older people were analyzed using a continuous-time, multi-state Markov model to estimate the probabilities of annual transitions into and out of each profile as well as the mean sojourn time in each profile. The probability of staying in a profile tended to decrease as profile severity increased. For profiles 5 and above, recovery to mild profiles 1, 2 and 3 was low, while annual probabilities of death and institutionalization were high (>0.10). The lower disability profiles (1 and 2) evidenced a mean profile sojourn time of over two years, contrary to sojourn times of 18 months or less with the other profiles. The probabilities are identifiable, indicating that a disability-based classification can characterize progression in older people. Since the required resources and costs are known for each profile, these probabilities are very helpful in planning home services for elderly populations. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  3. Profile of Home Care Aides, Nursing Home Aides, and Hospital Aides: Historical Changes and Data Recommendations

    ERIC Educational Resources Information Center

    Yamada, Yoshiko

    2002-01-01

    Purpose: To examine demographic characteristics and work conditions of home care aides, nursing home aides, and hospital aides in the late 1980s and late 1990s. Design and Methods: This study replicated a previous study which examined the Current Population Survey (CPS) March supplement from 1987 to 1989. The present study examined CPS data from…

  4. Demographic, epidemiological and nutritional profile of elders using home enteral nutritional therapy in Distrito Federal, Brazil.

    PubMed

    Salomon Zaban, Ana Lúcia Ribeiro; Garbi Novaes, Maria Rita Carvalho

    2009-09-01

    According to statistical projections of the World Health Organization, during the period between 1950 and 2025, the group of elderly in Brazil will have increased 15 times. Chronic-degenerative diseases are the illnesses that most affect the elderly population, directly related to the growing demand for Enteral Nutrition Therapy. The objective of this study was to analyze the demographic, epidemiological and nutritional profile of elderly patients assisted at the public hospitals in the Home Enteral Nutrition Therapy Program, of the State Health Department of Distrito Federal. This is a retroprospective, cross-sectional and analytical study, based on primary data, which enrolled 141 elderly patients who were prescribed home enteral nutrition. The collected variables corresponded to age, gender, clinical diagnosis, enteral route and nutritional status at the beginning of Home Enteral Nutrition Therapy. The association between variables was analyzed through the t-Student and chi-square tests, with a significance level of 0.05 and a Confidence Interval (CI) of 95%. There was a higher number of female patients (53.9%) when compared to male (46.1%), average age 75.82 years old for both groups. The most prevalent diseases were cerebro-vascular accident sequels and cancer (42.6% and 22.7% respectively). It was observed a prevalence of malnutrition equal to 69.7%, independent of age and gender. The most used enteral route was the nasal. Though Brazilian policies concerning assistance to the elderly have advanced during the last few years, the need for public policies for nutritional recovery of such patients persists, to promote a better quality of life for them.

  5. Cervical Cancer: paradigms at home and abroad

    Cancer.gov

    NCI funded a clinical trial that will have an impact on the treatment of late-stage cervical cancer, and also supported a screening trial in India using a network of community outreach workers offering low tech-screening by direct visualization of the cer

  6. Home-use cancer detecting band aid

    NASA Astrophysics Data System (ADS)

    Zalevsky, Zeev; Rudnitsky, Arkady; Sheinman, Victor; Tzoy, Andrey; Toktosunov, Aitmamat; Adashov, Arkady

    2016-03-01

    In this paper we present a novel concept in which special band aid is developed for early detection of cancer. The band aid contains an array of micro needles with small detection array connected to each needle which inspects the color of the surface of the skin versus time after being pinched with the needles. We were able to show in pre-clinical trials that the color varies differently if the skin is close to tumor tissue.

  7. Peptides homing to tumor vasculature: imaging and therapeutics for cancer.

    PubMed

    Liu, Zhiguo; Wu, Kaichun

    2008-11-01

    A major obstacle to advances in anti-vascular therapy is the lack of molecule candidates that are effective in selectively targeting cancer tissues while sparing normal ones. Phage display peptide library greatly eases the discovery of peptides with specific homing capacity. Many novel peptides homing to angiogenic vessels were isolated recently. Notably, many such peptides showed relatively specific affinity with particular tumor types. These peptides appear to be able to accumulate in the target vascular site of tumor, making them particularly efficient to deliver drugs or other therapeutic and imaging agents. Some homing peptides could not only target to the desired location, but also be internalized into targeted cells, or even induce destruction in desired cells all by the same peptide sequence itself. Accumulating evidence has shown that by tumor specific targeting delivery, improved local effect can be achieved with well tolerated side effects. In the current review, recent literatures and patents in this field have been summarized.

  8. Home - The Cancer Genome Atlas - Cancer Genome - TCGA

    Cancer.gov

    The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing.

  9. MALDI Profiling of Human Lung Cancer Subtypes

    PubMed Central

    Nistal, Manuel; Calvo, Enrique; Madero, Rosario; Díaz, Esther; Camafeita, Emilio; de Castro, Javier; López, Juan Antonio; González-Barón, Manuel; Espinosa, Enrique; Fresno Vara, Juan Ángel

    2009-01-01

    Background Proteomics is expected to play a key role in cancer biomarker discovery. Although it has become feasible to rapidly analyze proteins from crude cell extracts using mass spectrometry, complex sample composition hampers this type of measurement. Therefore, for effective proteome analysis, it becomes critical to enrich samples for the analytes of interest. Despite that one-third of the proteins in eukaryotic cells are thought to be phosphorylated at some point in their life cycle, only a low percentage of intracellular proteins is phosphorylated at a given time. Methodology/Principal Findings In this work, we have applied chromatographic phosphopeptide enrichment techniques to reduce the complexity of human clinical samples. A novel method for high-throughput peptide profiling of human tumor samples, using Parallel IMAC and MALDI-TOF MS, is described. We have applied this methodology to analyze human normal and cancer lung samples in the search for new biomarkers. Using a highly reproducible spectral processing algorithm to produce peptide mass profiles with minimal variability across the samples, lineal discriminant-based and decision tree–based classification models were generated. These models can distinguish normal from tumor samples, as well as differentiate the various non–small cell lung cancer histological subtypes. Conclusions/Significance A novel, optimized sample preparation method and a careful data acquisition strategy is described for high-throughput peptide profiling of small amounts of human normal lung and lung cancer samples. We show that the appropriate combination of peptide expression values is able to discriminate normal lung from non-small cell lung cancer samples and among different histological subtypes. Our study does emphasize the great potential of proteomics in the molecular characterization of cancer. PMID:19890392

  10. Serum lipid profile of breast cancer patients.

    PubMed

    Owiredu, W K B A; Donkor, S; Addai, B Wiafe; Amidu, N

    2009-02-15

    The purpose of this study was to carry out a comparative study to investigate the effect of lipid profile, oestradiol and obesity on the risk of a woman developing breast cancer. This study was carried out at the Komfo Anokye Teaching Hospital (KATH), Peace and Love Hospital, Oduom, Kumasi and Redeemed Clinic, Nima, Accra between May 2002 and March 2003. In this study, 200 consented women comprising 100 breast cancer patients (43 pre- and 57 post-menopausal) and 100 controls (45 pre- and 55 post-menopausal) with similar age range (25 to 80 years) were assessed for lipid profile, oestradiol and BMI. There was a significant increase in Body Mass Index (BMI) (p = 0.011), Total Cholesterol (TC) (p < 0.001), triglyceride (p = 0.026) and low density lipoprotein (LDL-cholesterol) (p = 0.001) of the breast cancer patients compared to the controls. With the exception of oestradiol (EST) that decreased, the lipid profile generally increased with age in both subjects and controls with the subjects having a much higher value than the corresponding control. There was also a significant positive correlation between BMI and TC (r2 = 0.022; p = 0.002) and also between BMI and LDL-cholesterol (r2 = 0.031; p = 0.0003). Apart from EST and LDL-cholesterol that were increased significantly only in the postmenopausal phase in comparison to the controls, BMI, TC and TG were increased in both pre-menopausal and post menopausal phases with HDL-cholesterol remaining unchanged. This study confirms the association between dyslipidaemia, BMI and increased breast cancer risk.

  11. Androgen receptor profiling predicts prostate cancer outcome

    PubMed Central

    Stelloo, Suzan; Nevedomskaya, Ekaterina; van der Poel, Henk G; de Jong, Jeroen; van Leenders, Geert JLH; Jenster, Guido; Wessels, Lodewyk FA; Bergman, Andries M; Zwart, Wilbert

    2015-01-01

    Prostate cancer is the second most prevalent malignancy in men. Biomarkers for outcome prediction are urgently needed, so that high-risk patients could be monitored more closely postoperatively. To identify prognostic markers and to determine causal players in prostate cancer progression, we assessed changes in chromatin state during tumor development and progression. Based on this, we assessed genomewide androgen receptor/chromatin binding and identified a distinct androgen receptor/chromatin binding profile between primary prostate cancers and tumors with an acquired resistance to therapy. These differential androgen receptor/chromatin interactions dictated expression of a distinct gene signature with strong prognostic potential. Further refinement of the signature provided us with a concise list of nine genes that hallmark prostate cancer outcome in multiple independent validation series. In this report, we identified a novel gene expression signature for prostate cancer outcome through generation of multilevel genomic data on chromatin accessibility and transcriptional regulation and integration with publically available transcriptomic and clinical datastreams. By combining existing technologies, we propose a novel pipeline for biomarker discovery that is easily implementable in other fields of oncology. PMID:26412853

  12. Immunity profile in breast cancer patients.

    PubMed

    Hrubisko, M; Sanislo, L; Zuzulova, M; Michalickova, J; Zeleznikova, T; Sedlak, J; Bella, V

    2010-01-01

    Despite the multifactorial pathogenesis of malignant transformation, it is assumed that deficiency in some immune mechanisms plays a considerable role in its development. Chronically activated immune cells exert tumour-promoting effects directly by influencing the proliferation and survival of neoplastic cells, as well as by indirect modulation of neoplastic microenvironments in favour of tumour progression. We refer to results of two separate investigations that aim to monitor the immune functions in patients with breast cancer. In the first investigation, we compare the picture of basic cellular immunity profile of patients in early stage of breast cancer with those suffering from advanced disease; in the second one, we compare the production of Th1-cytokines in patients in different stages of breast cancer and atopic healthy controls. We recognized that the totals of T-lymphocytes and T-helpers were lower and the expression of HLADR on T-lymphocytes were higher in patients with advanced disease; the expression of IL-2 and LFN-gamma by T-lymphocytes was decreased in metastatic breast cancer patients, however IL-2 production was increased in patients in early stage of disease. We conclude that the role of immune system in cancer development is ambivalent as it may be not only protective, but also harmful (Tab. 1, Fig. 3, Ref. 22). Full Text (Free, PDF) www.bmj.sk.

  13. Immune profiling and cancer post transplantation

    PubMed Central

    Hope, Christopher Martin; Coates, Patrick Toby H; Carroll, Robert Peter

    2015-01-01

    Half of all long-term (> 10 year) australian kidney transplant recipients (KTR) will develop squamous cell carcinoma (SCC) or solid organ cancer (SOC), making cancer the leading cause of death with a functioning graft. At least 30% of KTR with a history of SCC or SOC will develop a subsequent SCC or SOC lesion. Pharmacological immunosuppression is a major contributor of the increased risk of cancer for KTR, with the cancer lesions themselves further adding to systemic immunosuppression and could explain, in part, these phenomena. Immune profiling includes; measuring immunosuppressive drug levels and pharmacokinetics, enumerating leucocytes and leucocyte subsets as well as testing leucocyte function in either an antigen specific or non-specific manner. Outputs can vary from assay to assay according to methods used. In this review we define the rationale behind post-transplant immune monitoring assays and focus on assays that associate and/or have the ability to predict cancer and rejection in the KTR. We find that immune monitoring can identify those KTR of developing multiple SCC lesions and provide evidence they may benefit from pharmacological immunosuppressive drug dose reductions. In these KTR risk of rejection needs to be assessed to determine if reduction of immunosuppression will not harm the graft. PMID:25664246

  14. Electrochemical Genetic Profiling of Single Cancer Cells.

    PubMed

    Acero Sánchez, Josep Ll; Joda, Hamdi; Henry, Olivier Y F; Solnestam, Beata W; Kvastad, Linda; Akan, Pelin S; Lundeberg, Joakim; Laddach, Nadja; Ramakrishnan, Dheeraj; Riley, Ian; Schwind, Carmen; Latta, Daniel; O'Sullivan, Ciara K

    2017-03-21

    Recent understandings in the development and spread of cancer have led to the realization of novel single cell analysis platforms focused on circulating tumor cells (CTCs). A simple, rapid, and inexpensive analytical platform capable of providing genetic information on these rare cells is highly desirable to support clinicians and researchers alike to either support the selection or adjustment of therapy or provide fundamental insights into cell function and cancer progression mechanisms. We report on the genetic profiling of single cancer cells, exploiting a combination of multiplex ligation-dependent probe amplification (MLPA) and electrochemical detection. Cells were isolated using laser capture and lysed, and the mRNA was extracted and transcribed into DNA. Seven markers were amplified by MLPA, which allows for the simultaneous amplification of multiple targets with a single primer pair, using MLPA probes containing unique barcode sequences. Capture probes complementary to each of these barcode sequences were immobilized on a printed circuit board (PCB) manufactured electrode array and exposed to single-stranded MLPA products and subsequently to a single stranded DNA reporter probe bearing a HRP molecule, followed by substrate addition and fast electrochemical pulse amperometric detection. We present a simple, rapid, flexible, and inexpensive approach for the simultaneous quantification of multiple breast cancer related mRNA markers, with single tumor cell sensitivity.

  15. 'Genetic profiling' and ovarian cancer therapy (review).

    PubMed

    Vella, Nadia; Aiello, Marco; Russo, Alessia Erika; Scalisi, Aurora; Spandidos, Demetrios A; Toffoli, Giuseppe; Sorio, Roberto; Libra, Massimo; Stivala, Franca

    2011-01-01

    High variability observed among ovarian cancer patients in response to the same therapy and the related toxicity may be correlated to gene polymorphisms and genetic alterations affecting the metabolism of drugs commonly used to treat this tumor. Recent studies have shown a correlation between the polymorphisms characterizing GSTM1-T1 detoxifying enzymes and poor outcome in advanced ovarian cancer patients treated with platinum/paclitaxel-based chemotherapy. Multidrug resistance 1 (mdr-1) polymorphisms were found to be associated with resistance to paclitaxel treatment. Polymorphisms of MRP2, a protein involved in methotrexate, cisplatin and irinotecan active metabolite glucuronide transport, negatively affect platinum-based chemotherapy response. A similar occurrence has been observed with CYP1A1 Ile462Val and ercc1 C118T polymorphisms while patients who were carriers of MTHFR C677T polymorphism had a better response to methotrexate therapy, but an elevated risk of toxicity. Biological therapy with Bevacizumab, the anti-vascular endothelial growth factor has been shown to be less efficient in ovarian cancer patients carrying the polymorphism of the Interleukin-8 gene. Instead, polymorphisms in the XPD gene (Lys751Gln and Asp312Asn), a member of the nucleotide excision repair pathway, positively affects the response to therapy with carboplatin/paclitaxel. Therefore, the study of 'genetic profiling' is crucial to improving the clinician's ability to tailor effective therapy to the molecular profile of the patient while minimizing toxicities. This review describes clinical applications of the above genetic polymorphisms in ovarian cancer patients treated with platinum/paclitaxel-based chemotherapy.

  16. School-readiness profiles of children with language impairment: linkages to home and classroom experiences.

    PubMed

    Pentimonti, Jill M; Justice, Laura M; Kaderavek, Joan N

    2014-01-01

    This study represents an effort to advance our understanding of the nature of school readiness among children with language impairment (LI), a population of children acknowledged to be at risk of poor academic achievement. The academic, social-emotional, and behavioural competencies with which children arrive at kindergarten affect the nature of their future educational experiences, and their overall academic achievement. To examine whether there are reliable profiles that characterize children with LI just prior to kindergarten entrance, and the extent to which profile membership is associated with characteristics of children's homes and preschool experiences. Questions addressed were twofold: (1) To what extent are there reliable profiles of children with LI with respect to their school readiness? (2) To what extent is children's profile membership associated with characteristics of their homes and preschool classrooms? Participants were 136 children with LI from early childhood special education classrooms. We utilized latent class analysis (LCA) to classify individuals into profiles based on individual responses on school readiness measures. We then used multilevel hierarchical generalized linear models to examine the relations between profile membership and children's home/classroom experiences. LCA analyses revealed that a four-profile solution was the most appropriate fit for the data and that classroom experiences were predictive of these profiles, such that children in classrooms with more instructional/emotional support were more likely to be placed in profiles characterized by higher school readiness skills. These results suggest that the school readiness profiles of young children with LI are associated with the quality of children's classroom experiences, and that high-quality classroom experiences can be influential for ensuring that young children with LI arrive in kindergarten ready to learn. © 2014 Royal College of Speech and Language Therapists.

  17. Profile of nursing home residents with dementia who require assistance with mouth care.

    PubMed

    Jablonski, Rita A; Kolanowski, Ann M; Litaker, Mark

    2011-01-01

    The majority of nursing home residents require assistance with activities of daily living, including oral care. Poor oral health is common in the nursing home because residents are not given appropriate assistance to support this aspect of their care. The purpose of this study was to describe the demographic, functional, and behavioral profile of nursing home residents with dementia who require verbal or physical assistance with mouth care. Residents who required verbal support to complete mouth care exhibited higher levels of physical function, higher levels of cognitive functioning in the domains of language and executive function, lower levels of passivity, and higher scores for the personality trait of openness than residents who required physical assistance. Best practices for implementing verbal and physical assistance during mouth care to persons with dementia are presented on the basis of these profiles. Copyright © 2011 Mosby, Inc. All rights reserved.

  18. Profile of Nursing Home Residents With Dementia Who Require Assistance With Mouth Care

    PubMed Central

    Kolanowski, Ann M.; Litaker, Mark

    2011-01-01

    The majority of nursing home residents require assistance with activities of daily living, including oral care. Poor oral health is common in the nursing home because residents are not given appropriate assistance to support this aspect of their care. The purpose of this study was to describe the demographic, functional and behavioral profile of nursing home residents with dementia who require verbal or physical assistance with mouth care. Residents who required verbal support to complete mouth care exhibited higher levels of physical function, higher levels of cognitive functioning in the domains of language and executive function, lower levels of passivity, and higher scores for the personality trait of openness than residents who required physical assistance. Best practices for implementing verbal and physical assistance during mouth care to persons with dementia are presented based on these profiles. PMID:22055640

  19. Reading about Today's Homes and Gardens: A Subscriber Profile of a New Magazine.

    ERIC Educational Resources Information Center

    Garrison, Bruce

    A study examined readership and consumer patterns for subscribers of a new upscale home and garden magazine, in order to construct a demographic profile of the typical subscriber and to determine the magazine content preferred by these subscribers, as well as the lifestyle maintained by these individuals. Subjects, 603 randomly selected…

  20. A Profile of Home Care Workers from the 2000 Census: How It Changes What We Know

    ERIC Educational Resources Information Center

    Montgomery, Rhonda J. V.; Holley, Lyn; Deichert, Jerome; Kosloski, Karl

    2005-01-01

    Purpose: The goal of our study was to identify a representative sample of direct care aides to generate an accurate profile of the long-term-care workforce, with a special focus on home care workers. Design and Methods: Data were taken from the 5% Public Use Microdata Sample (PUMS) of the 2000 Census. Results: Variable coding in the 2000 Census…

  1. Opportunities-to-Learn at Home: Profiles of Students With and Without Reaching Science Proficiency

    NASA Astrophysics Data System (ADS)

    Liu, Xiufeng; Whitford, Melinda

    2011-08-01

    This study examines the relationship between opportunity-to-learn (OTL) at home and students' attainment of science proficiency. The data set used was the 2006 PISA science US national sample. Data mining was used to create patterns of association between home OTL variables and student attainment of science proficiency. It was found that students who failed to reach science proficiency are characterized by having fewer than 100 books at home; these students are also found to take out-of-school individual or group lessons with their teachers or with other teachers. On the other hands, students who reached science proficiency are characterized by having more than 100 books at home, not taking any out-of-school lessons, and having a highest parent level of graduate education. In addition to the above common characteristics, other home characteristics (e.g. computer and internet at home and language spoke at home) are also identified in profiles of students who have reached science proficiency. We explain the above findings in terms of current social-cultural theories. We finally discuss implications of the above findings for future studies and for improving science education policy and practice.

  2. Do Women with Inoperable Breast Cancer Have a Psychological Profile?

    ERIC Educational Resources Information Center

    Gilbar, Ora; Florian, Victor

    1991-01-01

    Compared psychological variables of 30 patients with inoperable breast cancer to matched group of 30 operable breast cancer patients. Found that women with inoperable breast cancer had higher scores in denial, exhaustion, hopelessness, worthlessness, depression, somatization, hostility, and psychoticism. Profile of inoperable cancer patients did…

  3. Gene expression profiles in irradiated cancer cells

    SciTech Connect

    Minafra, L.; Bravatà, V.; Russo, G.; Ripamonti, M.; Gilardi, M. C.

    2013-07-26

    Knowledge of the molecular and genetic mechanisms underlying cellular response to radiation may provide new avenues to develop innovative predictive tests of radiosensitivity of tumours and normal tissues and to improve individual therapy. Nowadays very few studies describe molecular changes induced by hadrontherapy treatments, therefore this field has to be explored and clarified. High-throughput methodologies, such as DNA microarray, allow us to analyse mRNA expression of thousands of genes simultaneously in order to discover new genes and pathways as targets of response to hadrontherapy. Our aim is to elucidate the molecular networks involved in the sensitivity/resistance of cancer cell lines subjected to hadrontherapy treatments with a genomewide approach by using cDNA microarray technology to identify gene expression profiles and candidate genes responsible of differential cellular responses.

  4. Gene expression profiles in irradiated cancer cells

    NASA Astrophysics Data System (ADS)

    Minafra, L.; Bravatà, V.; Russo, G.; Ripamonti, M.; Gilardi, M. C.

    2013-07-01

    Knowledge of the molecular and genetic mechanisms underlying cellular response to radiation may provide new avenues to develop innovative predictive tests of radiosensitivity of tumours and normal tissues and to improve individual therapy. Nowadays very few studies describe molecular changes induced by hadrontherapy treatments, therefore this field has to be explored and clarified. High-throughput methodologies, such as DNA microarray, allow us to analyse mRNA expression of thousands of genes simultaneously in order to discover new genes and pathways as targets of response to hadrontherapy. Our aim is to elucidate the molecular networks involved in the sensitivity/resistance of cancer cell lines subjected to hadrontherapy treatments with a genomewide approach by using cDNA microarray technology to identify gene expression profiles and candidate genes responsible of differential cellular responses.

  5. Home-based multidimensional survivorship programmes for breast cancer survivors.

    PubMed

    Cheng, Karis Kin Fong; Lim, Yee Ting Ethel; Koh, Zhi Min; Tam, Wilson Wai San

    2017-08-24

    The prognosis and survival rate of women with breast cancer have significantly improved worldwide. Effective home-based multidimensional programmes for breast cancer survivors have gained an ever greater emphasis in survivorship care to maximise women's quality of life for their successful transition to rehabilitation and normal life. It is important to summarise the best available evidence to evaluate the effects of home-based multidimensional survivorship programmes on quality of life in women within 10 years of the completion of surgery or adjuvant cancer therapy for breast cancer, or both. To assess the effects of home-based, multidimensional survivorship (HBMS) programmes on maintaining or improving the quality of life in breast cancer survivors. In April 2016 we searched the Cochrane Breast Cancer Specialised Register, CENTRAL, PubMed, Embase, CINAHL Plus, PsycINFO, Web of Science, and the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov. We also screened reference lists of all identified studies and contacted study authors. Randomised controlled trials (RCTs) and quasi-RCTs assessing the effects of HBMS programmes in maintaining or improving quality of life in women with stages 0 to 3 breast cancer who completed primary cancer treatment (surgery or adjuvant cancer therapy, or both) up to 10 years earlier. We considered studies where the interventions included more than one of the following listed components: educational (such as information provision and self-management advice), physical (such as exercise training and resistance training) and psychological (such as counselling and cognitive therapies), to constitute a multidimensional programme. Interventions had to be allowed to be carried out at home. Two authors independently assessed eligible studies for inclusion, and performed quality assessment and extracted relevant data of the included studies. Quality of life was the primary outcome of

  6. Personal Web home pages of adolescents with cancer: self-presentation, information dissemination, and interpersonal connection.

    PubMed

    Suzuki, Lalita K; Beale, Ivan L

    2006-01-01

    The content of personal Web home pages created by adolescents with cancer is a new source of information about this population of potential benefit to oncology nurses and psychologists. Individual Internet elements found on 21 home pages created by youths with cancer (14-22 years old) were rated for cancer-related self-presentation, information dissemination, and interpersonal connection. Examples of adolescents' online narratives were also recorded. Adolescents with cancer used various Internet elements on their home pages for cancer-related self-presentation (eg, welcome messages, essays, personal history and diary pages, news articles, and poetry), information dissemination (e.g., through personal interest pages, multimedia presentations, lists, charts, and hyperlinks), and interpersonal connection (eg, guestbook entries). Results suggest that various elements found on personal home pages are being used by a limited number of young patients with cancer for self-expression, information access, and contact with peers.

  7. Profiles of nursing home residents with multiple sclerosis using the minimum data set.

    PubMed

    Buchanan, R J; Wang, S; Huang, C; Graber, D

    2001-06-01

    This paper profiles nursing home residents with multiple sclerosis (MS) at the time of admission, including sociodemographic characteristics, health status measures, and treatments received. Admission assessments from the Minimum Data Set are used to create these profiles of residents with MS. There are 9,013 admission assessments in the MDS for residents with MS between June 22, 1998 and January 17, 2000 analyzed for this study. Residents with MS are distinctly younger at admission than most nursing home residents, averaging 57.98 years of age. Recently admitted residents with MS are more physically dependent than other nursing home residents and tend to have limited range of motion and loss of voluntary movement About one in three newly admitted residents with MS had some degree of impaired cognitive function. Over one third of residents with MS were depressed at admission, yet only 11.7% of recently admitted residents with MS were evaluated by a licensed mental health specialist This prompts concem about the psychosocial well-being of MS residents in nursing homes.

  8. Loneliness and coping among tertiary-level adult cancer patients in the home.

    PubMed

    Perry, G R

    1990-10-01

    This exploratory study measured the degree of loneliness experienced by adult cancer patients. All were in the initial phases of the illness, that is, currently receiving treatment consisting of either chemotherapy or radiation therapy on an outpatient basis and/or recuperating from surgery in the home setting. All were within 100 days of initial diagnosis of cancer. The UCLA Loneliness Scale by Peplau was used in measuring loneliness. In addition, the coping methods of this same group of patients were examined using the Jalowiec Coping Scale to determine predominant methods of coping with the situational crisis imposed by cancer diagnosis and treatment. The instruments were administered in the home or in an outpatient setting and patients were accessed through cancer treatment centers and from oncologists in the southern Illinois area. The study was conducted to determine the prevalence of loneliness, to identify predominant coping methods, and to discern the relationship, if any, between coping methods employed and the degree of loneliness reported by the adult cancer patients. The conceptual framework chosen for the study was taken from the work of Lazarus and Jalowiec with regard to coping; the work of Peplau, Russell, and Cutrone on loneliness formed the conceptual basis for the portion of the study regarding that dimension. A total of 41 cancer patients were surveyed--21 were male and 20 were female. The median age was 60 years, and the mean educational level was 10.5 years. There were significant differences found between loneliness scores by age categories and by marital status, as well as a relationship between membership in organizations and loneliness scores. There were significant relationships found between coping methods (confrontive, emotive, palliative) employed and the degree of loneliness experienced by these cancer patients. Coping methods were also ranked by frequency of use, and interesting patterns emerged--especially noteworthy were group

  9. Home versus hospital mortality from cancer in Mexico (1999-2009).

    PubMed

    Castillo-Guzmán, Sandra; Palacios-Ríos, Dionicio; Nava-Obregón, Teresa Adriana; Torres-Pérez, Juan Francisco; González-Santiago, Omar

    2013-05-01

    To analyze the place of death from cancer in México from 1999 to 2009 and find the associated factors. We collected data on mortality by cancer from the national database including age, gender, area of residence, level of education, place of death, and type of cancer. The proportion of deaths at home and hospital was 55.67% and 39%, respectively. Factors associated with home deaths were old age, female gender, rural area of residence, and lack of formal education. There was a short but significant decrease in home deaths for cervical cancer and leukemia. In México, mortality in home is greater than in hospital for patients with cancer. Our results have important implications for palliative care professionals and health services of México.

  10. Pain management at home in children with cancer: a daily diary study.

    PubMed

    Fortier, Michelle A; Wahi, Aditi; Bruce, Colette; Maurer, Eva L; Stevenson, Robert

    2014-06-01

    With the transition of care of cancer patients from the hospital to the home setting, parents are largely responsible for children's pain management. Children's cancer pain is undermanaged, yet, there is little empirical data on the occurrence and management of cancer pain in the home setting. The purpose of the present study, therefore, was to employ a daily diary protocol to examine barriers to pain management of children's cancer pain by parents at home. Parent-child dyads were recruited from the Cancer Institute at a major children's hospital in Southern California. A total of 45 patient/parent pairs completed baseline data on demographic and personality characteristics, children's quality of life, and parental beliefs regarding analgesic use for children and then completed daily diaries of pain and analgesic administration for 14 consecutive days. Most children were reported to experience chronic pain while undergoing treatment for cancer, yet overall analgesic administration at home was low. Parents who reported misconceptions regarding analgesic use for children were less likely to administer pain medication to children. Children who were less shy, more social, or had lower quality of life were more likely to receive analgesics. A significant proportion of children receiving outpatient treatment for cancer were rated as experiencing chronic pain and pain was not optimally managed in the home setting. Further understanding and addressing barriers to children's cancer pain management in the home setting will aid in alleviating unnecessary pain in this vulnerable patient population. © 2013 Wiley Periodicals, Inc.

  11. Molecular Profiling of Clear Cell Ovarian Cancers

    PubMed Central

    Friedlander, Michael L.; Russell, Kenneth; Millis, Sherri; Gatalica, Zoran; Bender, Ryan; Voss, Andreas

    2016-01-01

    Background Advanced stage/recurrent clear cell ovarian cancers (CCOCs) are characterized by a low response to chemotherapy and a poor prognosis. There is growing interest in investigating novel/molecular targeted therapies in patients with CCOC in histotype-specific trials. However, CCOCs are not a uniform entity and comprise a number of molecular subtypes and it is unlikely that a single approach to treatment will be appropriate for all patients. The aim of this study was to analyze the results of a multiplatform profiling panel in CCOCs to identify potential therapeutic targets. Patients and Methods Tumor profiling was performed on 521 CCOCs. They were grouped into pure (n = 422) and mixed (n = 99) CCOC for analysis. Testing included a combination of DNA sequencing (including next-generation sequencing) using a 46-gene panel, immunohistochemistry, fluorescent or chromogenic in situ hybridization, and RNA fragment analysis. Results The most common findings were in the PIK3CA/Akt/mTOR pathway, with 61% of all CCOCs showing a molecular alteration in one of these pathway components. Next-generation sequencing revealed PIK3CA mutations in 50% of pure CCOCs. Significant differences were observed between pure and mixed CCOCs with respect to hormone receptor expression (9% vs 34.7% for ER, 13.45 vs 26.4% for PR), cMET (24.1% vs 11.6%), PD-1 tumor infiltrating lymphocytes (48.1% vs 100%), expression of PD-L1 (7.4% vs 25%), and TOPO1 (41% vs 27.1%) on immunohistochemistry, whereas next-generation sequencing revealed significant differences in mutation frequency in PIK3CA (50% vs 18.5%), TP53 (18.1% vs 57.7%), KRAS (12.4% vs 3.7%), and cMET (1.9% vs 11.1%). Conclusions This large study confirms that the PIK3CA/Akt/mTOR pathway is commonly altered in CCOCs, and highlights the significant differences between pure and mixed CCOCs. Clear cell ovarian cancers are molecularly heterogeneous and there are a number of potential therapeutic targets which could be tested in clinical

  12. From ABCs to DVDs: Profiles of Infants' Home Media Environments in the First Two Years of Life

    ERIC Educational Resources Information Center

    Mol, Suzanne E.; Neuman, Susan B.; Strouse, Gabrielle A.

    2014-01-01

    The very definition of print exposure has evolved in recent years as has the production of new media for infants and toddlers. Recognising that parents now have a confluence of media to select from, our study was designed to provide a richer understanding of home-literacy environments among 100 infants. Three profiles of families' home media…

  13. From ABCs to DVDs: Profiles of Infants' Home Media Environments in the First Two Years of Life

    ERIC Educational Resources Information Center

    Mol, Suzanne E.; Neuman, Susan B.; Strouse, Gabrielle A.

    2014-01-01

    The very definition of print exposure has evolved in recent years as has the production of new media for infants and toddlers. Recognising that parents now have a confluence of media to select from, our study was designed to provide a richer understanding of home-literacy environments among 100 infants. Three profiles of families' home media…

  14. Health-related profile and quality of life among nursing home residents: does pain matter?

    PubMed

    Tse, Mimi M Y; Wan, Vanessa T C; Vong, Sinfia K S

    2013-12-01

    The purpose of this exploratory cross-sectional study was to explore the health-related profile and quality of life among older persons living with and without pain in nursing homes. Ten nursing homes were approached, and 535 older persons were invited to join the study from 2009 to 2011. The nursing home residents' demographic information and information regarding their pain situation and the use of oral analgesic drug and nondrug therapy among the older residents with chronic pain were also collected. Residents' physical health (using the Barthel Activities of Daily Living (ADL) and Elderly Mobility Scores); psychologic health, including happiness, life satisfaction, depression, and loneliness (using the Happiness Scale, the Life Satisfaction Scale, the Geriatric Depression Scale, and the UCLA Loneliness Scale); and quality of life were investigated. Among the 535 nursing home residents, 396 (74%) of them suffered from pain, with mean pain scores of 4.09 ± 2.19, indicating medium pain intensity a remaining 139 (26%) reported no pain. The location of pain was mainly in the knees, back and shoulders. Our results demonstrated that, with the exception of the no-pain group (p < .05), nursing home residents' pain affected both their psychologic health, including happiness, life satisfaction, and depression, and their physical quality of life. Nevertheless, only one-half of the older persons with pain used oral analgesic drug or nondrug therapy to relieve their pain. Pain had a significant impact on their mobility and ADL, was positively correlated with happiness and life satisfaction, and was negatively correlated with loneliness and depression. Pain management is a high priority in elderly care; as such, innovative and interdisciplinary strategies are necessary to enhance quality of life particularly for older persons living in nursing homes.

  15. Microbiological and clinical profiles of patients with microbial keratitis residing in nursing homes.

    PubMed

    Jhanji, V; Constantinou, M; Taylor, H R; Vajpayee, R B

    2009-12-01

    To study the microbiological and clinical profile of patients with microbial keratitis living in nursing homes. A retrospective analysis of hospital records from 1996 to 2006 of patients who had microbial keratitis, and were living in nursing homes, was undertaken. The main parameters evaluated were clinical and microbiological profile and final visual outcome. Of 66 patients included in this study, 39 were female and 27 were male, with mean age of 81(SD 11) (range 46-97) years. The major ocular and systemic factors associated with the occurrence of microbial keratitis were the presence of dry eyes (26%) and rheumatoid arthritis (81%), respectively. A positive bacterial culture was obtained in 54 (82%) cases with Staphylococcus being the most prevalent isolate (48%). Seven patients had positive culture for herpes virus. Surgical intervention had to be performed in 31(47%) of cases mainly in the form of botox injection for induction of ptosis (n = 9, 27%), keratoplasty (n = 8, 24%), tarsorrhaphy (n = 5, 15%) or glue (n = 3, 9%). The mean pre-treatment and post-treatment visual acuity was counting fingers and 6/60 respectively. Microbial keratitis in patients living in nursing homes is usually caused by Staphylococcus and is associated with dry eyes and ocular surface disease. Surgical intervention is required in majority of cases with poor visual outcome.

  16. Chemical characterization of indoor air of homes from communes in Xuan Wei, China, with high lung cancer mortality rate

    NASA Astrophysics Data System (ADS)

    Chuang, J. C.; Cao, S. R.; Xian, Y. L.; Harris, D. B.; Mumford, J. L.

    In a rural county, Xuan Wei, China, the lung cancer mortality rate is among China's highest, especially in women. This mortality rate is more associated with indoor air burning of smoky coal, as opposed to smokeless coal or wood, for cooking and heating under unvented conditions. Homes using different fuels from communes with high and low lung cancer mortality rates were sampled for particulate matter (< 10 μm) and semivolatile organics. The fine particles obtained from homes using smoky coal contained highest concentrations of organic matter (> 70%), including PAH, followed by homes using wood and smokeless coal. The major components present in the smoky coal filter samples were PAH and alkylated PAH. The smokeless coal filter samples exhibited profiles which were similar to the smoky coal samples except that some sulfur compounds were found. The estimated concentration levels of PAH in the smokeless coal samples were about one to two orders of magnitude lower than those of the smoky coal samples. In addition to PAH, aliphatic compounds and fatty acids were the major components found in the wood samples. Selected sample extracts from homes using smoky coal were fractionated into four fractions, and the results showed that the PAH and polar fractions have high mutagenic activity. Chemical characterization of the PAH fraction indicated that concentrations of some alkylated PAH were higher than those of their parent compounds. Chemical characterization of the polar fractions showed that nitrogen heterocyclic compounds are present.

  17. Molecular Profiling of Prostate Cancer Specimens Using Multicolor Quantum Dots

    DTIC Science & Technology

    2009-02-01

    0117 TITLE: Molecular profiling of prostate cancer specimens using Multicolor Quantum Dots PRINCIPAL INVESTIGATOR: Xiaohu Gao...profiling of prostate cancer specimens using Multicolor Quantum Dots 5a. CONTRACT NUMBER W81XWH-07-1-0117 5b. GRANT NUMBER PC061345 5c...based on the biology of their tumors. We proposed to develop oligonucleotide tagged quantum dots and antibodies for multiplexed imaging of prostate

  18. Risk Profiling May Improve Lung Cancer Screening

    Cancer.gov

    A new modeling study suggests that individualized, risk-based selection of ever-smokers for lung cancer screening may prevent more lung cancer deaths and improve the effectiveness and efficiency of screening compared with current screening recommendations

  19. Transferring intercellular signals and traits between cancer cells: extracellular vesicles as "homing pigeons".

    PubMed

    Cesi, Giulia; Walbrecq, Geoffroy; Margue, Christiane; Kreis, Stephanie

    2016-06-10

    Extracellular vesicles are cell-derived vesicles, which can transport various cargos out of cells. From their cell of origin, the content molecules (proteins, non-coding RNAs including miRNAs, DNA and others) can be delivered to neighboring or distant cells and as such extracellular vesicles can be regarded as vehicles of intercellular communication or "homing pigeons". Extracellular vesicle shuttling is able to actively modulate the tumor microenvironment and can partake in tumor dissemination. In various diseases, including cancer, levels of extracellular vesicle secretion are altered resulting in different amounts and/or profiles of detectable vesicular cargo molecules and these distinct content profiles are currently being evaluated as biomarkers. Apart from their potential as blood-derived containers of specific biomarkers, the transfer of extracellular vesicles to surrounding cells also appears to be involved in the propagation of phenotypic traits. These interesting properties have put extracellular vesicles into the focus of many recent studies.Here we review findings on the involvement of extracellular vesicles in transferring traits of cancer cells to their surroundings and briefly discuss new data on oncosomes, a larger type of vesicle. A pressing issue in cancer treatment is rapidly evolving resistance to many initially efficient drug therapies. Studies investigating the role of extracellular vesicles in this phenomenon together with a summary of the technical challenges that this field is still facing, are also presented. Finally, emerging areas of research such as the analysis of the lipid composition on extracellular vesicles and cutting-edge techniques to visualise the trafficking of extracellular vesicles are discussed.

  20. LUNG CANCER IN NEVER SMOKERS: MOLECULAR PROFILES AND THERAPEUTIC IMPLICATIONS

    PubMed Central

    Rudin, Charles M.; Avila-Tang, Erika; Harris, Curtis C.; Herman, James G.; Hirsch, Fred R.; Pao, William; Schwartz, Ann G.; Vahakangas, Kirsi H.; Samet, Jonathan M.

    2010-01-01

    The majority of lung cancers are caused by long term exposure to the several classes of carcinogens present in tobacco smoke. While a significant fraction of lung cancers in never smokers may also be attributable to tobacco, many such cancers arise in the absence of detectable tobacco exposure, and may follow a very different cellular and molecular pathway of malignant transformation. Recent studies summarized here suggest that lung cancers arising in never smokers have a distinct natural history, profile of oncogenic mutations, and response to targeted therapy. The majority of molecular analyses of lung cancer have focused on genetic profiling of pathways responsible for metabolism of primary tobacco carcinogens. Limited research has been conducted evaluating familial aggregation and genetic linkage of lung cancer, particularly among never smokers in whom such associations might be expected to be strongest. Data emerging over the past several years demonstrates that lung cancers in never smokers are much more likely to carry activating mutations of the Epidermal Growth Factor Receptor (EGFR), a key oncogenic factor and direct therapeutic target of several newer anti-cancer drugs. EGFR mutant lung cancers may represent a distinct class of lung cancers, enriched in the never smoking population, and less clearly linked to direct tobacco carcinogenesis. These insights followed initial testing and demonstration of efficacy of EGFR-targeted drugs. Focused analysis of molecular carcinogenesis in lung cancers in never smokers is needed, and may provide additional biologic insight with therapeutic implications for lung cancers in both ever smokers and never smokers. PMID:19755392

  1. Can This Patient Be Discharged Home? Factors Associated With At-Home Death Among Patients With Cancer

    PubMed Central

    Alonso-Babarro, Alberto; Bruera, Eduardo; Varela-Cerdeira, María; Boya-Cristia, María Jesús; Madero, Rosario; Torres-Vigil, Isabel; De Castro, Javier; González-Barón, Manuel

    2011-01-01

    Purpose The purpose of this study was to identify factors associated with at-home death among patients with advanced cancer and create a decision-making model for discharging patients from an acute-care hospital. Patients and Methods We conducted an observational cohort study to identify the association between place of death and the clinical and demographic characteristics of patients with advanced cancer who received care from a palliative home care team (PHCT) and of their primary caregivers. We used logistic regression analysis to identify the predictors of at-home death. Results We identified 380 patients who met the study inclusion criteria; of these, 245 patients (64%) died at home, 72 (19%) died in an acute-care hospital, 60 (16%) died in a palliative care unit, and three (1%) died in a nursing home. Median follow-up was 48 days. We included the 16 variables that were significant in univariate analysis in our decision-making model. Five variables predictive of at-home death were retained in the multivariate analysis: caregiver's preferred place of death, patients' preferred place of death, caregiver's perceived social support, number of hospital admission days, and number of PHCT visits. A subsequent reduced model including only those variables that were known at the time of discharge (caregivers' preferred place of death, patients' preferred place of death, and caregivers' perceived social support) had a sensitivity of 96% and a specificity of 81% in predicting place of death. Conclusion Asking a few simple patient- and family-centered questions may help to inform the decision regarding the best place for end-of-life care and death. PMID:21343566

  2. The behavioural homing response of adult chum salmon Oncorhynchus keta to amino-acid profiles.

    PubMed

    Chen, E Y; Leonard, J B K; Ueda, H

    2016-11-21

    Adult chum salmon Oncorhynchus keta homing behaviour in a two-choice test tank (Y-maze) was monitored using a passive integrated transponder (PIT)-tag system in response to river-specific dissolved free amino-acid (DFAA) profiles and revealed that the majority of O. keta showed a preference for artificial natal-stream water and tended to stay in this maze arm for a longer period; natal-stream water was chosen over a nearby tributary's water, but not when the O. keta were presented with a non-tributary water. The results demonstrate the ability of O. keta to discriminate artificial stream waters containing natural levels of DFAA.

  3. Radon, Secondhand Smoke, and Children in the Home: Creating a Teachable Moment for Lung Cancer Prevention.

    PubMed

    Huntington-Moskos, Luz; Rayens, Mary Kay; Wiggins, Amanda; Hahn, Ellen J

    2016-11-01

    This study determined whether having minor children in the home was associated with the teachable moment (TM) constructs of lung cancer worry, perceived risk, health-related self-concept, and the novel construct of synergistic risk. Secondary data analysis of baseline data from a randomized controlled trial of an intervention to reduce home exposure to radon and secondhand smoke (SHS). Quota sample of adults recruited at a Central Kentucky academic medical center (N = 556). Survey items assessed lung cancer worry, perceived risk, synergistic risk perception, and health-related self-concept. The presence of children in the home was not a significant predictor of any construct needed to create a TM for lung cancer prevention. Individuals with children living in the home were more likely to be younger, a racial/ethnic minority, a current smoker, and live with a smoker compared to those without children in the home. There is a critical need to raise parental awareness on child health inequities related to the home exposure to radon and SHS. Public health nurses can create TMs for lung cancer prevention through greater awareness of the risks posed by radon and SHS along with promoting home testing and low-cost resources to reduce risk. © 2016 Wiley Periodicals, Inc.

  4. [Promotion of home shifts for terminal cancer patients through intervention of visitor palliative care team].

    PubMed

    Shiraishi, Ko; Chigira, Mayumi; Tsuyuki, Naoko; Hozaki, Kyoko; Murotsu, Keizo; Umeki, Mikiko; Harada, Naohiro; Hirata, Satomi; Otsuka, Yuko; Hara, Hiroko

    2013-12-01

    It has been recommended that terminal cancer patients be shifted from the hospital to their homes. In our hospital, a visitor palliative care team was started for the purpose of the early introduction of palliative care, and home shifts were promoted. The results of home shifts by the visitor palliative care team from 2008 to 2012 were examined. Home shifts were possible for 27 cases out of 108 cases intervened. In 12 cases, there were at-home deaths, and the median at-home period was 55 days. In the group that could not be shifted, the at-home death rate and application rate of nursing care insurance were low. Additionally, the length of stay (median) for patients who died in hospitalization was 8 days for the group that could be shifted and 17 days for the group that could not be shifted. It was felt that effective communication with local health care facilities is important for a successful home shift. Early and adequate preparations for the treatment and care of terminal cancer patients undergoing home shift are important, and in this regard, a review of the current provisions of nursing care insurance is necessary.

  5. Effect of home care service on the quality of life in patients with gynecological cancer.

    PubMed

    Aktas, Demet; Terzioglu, Fusun

    2015-01-01

    The purpose of the research was to determine the effect of home care service on the quality of life in patients with gynecological cancer. This randomized case control study was carried out in a womans hospital between September 2011 and February 2012. Women undergoing gynecological cancer treatment were separated into intervention and control groups, of 35 patients each. The intervention group was provided with nursing care service through hospital and home visits (1st, 12th weeks) within the framework of a specifically developed nursing care plan. The control group was monitored without any intervention through the hospital routine protocols (1st, 12th weeks). Data were collected using An Interview Form, Home Visit Monitoring Form and Quality of Life Scale/Cancer Survivors. Effects of home care service on the quality of life in gynecological cancer patients were investigated using chi-square tests, McNemar's test, independent t-test and ANOVA. This study found that the intervention group receiving home care service had a moderately high quality of life (average mean: 6.01±0.64), while the control group had comparatively lower quality (average mean: 4.35±0.79) within the 12 week post- discharge period (p<0.05). This study found home care services to be efficient in improving the quality of life in patients with gynecological cancer.

  6. Marie Curie nurses: enabling patients with cancer to die at home.

    PubMed

    Higginson, Irene J; Wilkinson, Susie

    2002-05-01

    Marie Curie Cancer Care established its nursing service in 1958; however, the service has had little formal evaluation. This study aimed to describe and evaluate the care provided by Marie Curie nurse, and in particular to determine whether patients in their care remained and died at home. Two existing data sets were used: data on all patients referred to the Marie Curie Nursing Services in 147 areas of England, Wales, Scotland and Northern Ireland for 26 months, and data on cancer death registrations in England. A request for a Marie Curie nurse was made for 26,632 patients, 97% of whom had cancer and 11% of whom lived alone. The amount of care provided varied enormously (<1 hour-2862 hours), although the vast majority of patients less than 300 hours of nursing care. Place of death was recorded for only half these patients; 94% died at home, 2.5% in a hospice, 2.3% in a hospital, 0.2% in a nursing home and 0.6% other. Home death was most often associated with patients receiving medication via a syringe driver, patients living with other people, patients with cancer, other than prostate cancer, shorter time between referral and death and younger age. The results lend support to the theory that the care given to patients in their homes by Marie Curie nurses facilitated home death for many patients. Services need to ensure that mechanisms are in place to achieve data collection. Rigorous prospective evaluation is needed in the future.

  7. Tumor homing peptides as molecular probes for cancer therapeutics, diagnostics and theranostics.

    PubMed

    Gautam, A; Kapoor, P; Chaudhary, K; Kumar, R; Raghava, G P S

    2014-01-01

    Cancer is one of the leading causes of mortality worldwide, with more than 10 million new cases each year. Despite the presence of several anticancer agents, cancer treatment is still not very effective. Main reasons behind this high mortality rate are the lack of screening tests for early diagnosis, and non-availability of tumor specific drug delivery system. Most of the current anticancer drugs are unable to differentiate between cancerous and normal cells, leading to systemic toxicity, and adverse side effects. In order to tackle this problem, a considerable progress has been made over the years to identify peptides, which specifically bind to the tumor cells, and tumor vasculature (tumor homing peptides). With the advances in phage display technology, and combinatorial libraries like one-bead one-compound library, several hundreds of tumor homing peptides, and their derivatives, which have potential to detect tumor in vivo, and deliver anticancer agents specifically to the tumor site, have been discovered. Currently, many tumor homing peptide-based therapies for cancer treatment and diagnosis are being tested in various phases of clinical trials. In this review, we have discussed the progress made so far in the identification of tumor homing peptides, and their applications in cancer therapeutics, diagnosis, and theranostics. In addition, a brief discussion on tumor homing peptide resource, and in silico designing of tumor homing peptides has also been provided.

  8. Assessment of the impact of cancer on work, recreation, home management and sleep using a general health status measure.

    PubMed Central

    Malone, M; Harris, A L; Luscombe, D K

    1994-01-01

    A general health status measure (the UK Sickness Impact Profile) was used to assess health-related quality of life in 212 cancer patients [143 women, mean (SD-standard deviation) age 55.3 (11.7) years] compared to 105 age-sex matched control subjects [71 women, mean (SD) age 54.7 (12.2) years]. The four main areas of impairment in the cancer patient group were work, recreation and pastimes, home management and sleep and rest. The majority of patients were unable to work or working shorter hours due to their disease. A diagnosis of cancer was likewise found to have a major impact on active leisure pursuits and led to reduced participation in social and community activities. Patients had particular problems in carrying out household chores and maintenance or repair work in the house. Many patients had difficulty sleeping at night and tended to sleep during the day or rest for much of the day. The majority of studies of quality of life in oncology patients concentrate upon alterations in symptoms, such measures would fail to detect impairment in the aspects described above. Greater attention should be directed towards addressing issues such as changes in employment status and the need for help in the home to improve the overall care of cancer patients. PMID:8046723

  9. Metabolic Risk Profile and Cancer in Korean Men and Women.

    PubMed

    Ko, Seulki; Yoon, Seok-Jun; Kim, Dongwoo; Kim, A-Rim; Kim, Eun-Jung; Seo, Hye-Young

    2016-05-01

    Metabolic syndrome is a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease. Associations between metabolic syndrome and several types of cancer have recently been documented. We analyzed the sample cohort data from the Korean National Health Insurance Service from 2002, with a follow-up period extending to 2013. The cohort data included 99 565 individuals who participated in the health examination program and whose data were therefore present in the cohort database. The metabolic risk profile of each participant was assessed based on obesity, high serum glucose and total cholesterol levels, and high blood pressure. The occurrence of cancer was identified using Korean National Health Insurance claims data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for age group, smoking status, alcohol intake, and regular exercise. A total of 5937 cases of cancer occurred during a mean follow-up period of 10.4 years. In men with a high-risk metabolic profile, the risk of colon cancer was elevated (HR, 1.40; 95% CI, 1.14 to 1.71). In women, a high-risk metabolic profile was associated with a significantly increased risk of gallbladder and biliary tract cancer (HR, 2.05; 95% CI, 1.24 to 3.42). Non-significantly increased risks were observed in men for pharynx, larynx, rectum, and kidney cancer, and in women for colon, liver, breast, and ovarian cancer. The findings of this study support the previously suggested association between metabolic syndrome and the risk of several cancers. A high-risk metabolic profile may be an important risk factor for colon cancer in Korean men and gallbladder and biliary tract cancer in Korean women.

  10. Metabolic Risk Profile and Cancer in Korean Men and Women

    PubMed Central

    Kim, A-Rim; Kim, Eun-Jung; Seo, Hye-Young

    2016-01-01

    Objectives: Metabolic syndrome is a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease. Associations between metabolic syndrome and several types of cancer have recently been documented. Methods: We analyzed the sample cohort data from the Korean National Health Insurance Service from 2002, with a follow-up period extending to 2013. The cohort data included 99 565 individuals who participated in the health examination program and whose data were therefore present in the cohort database. The metabolic risk profile of each participant was assessed based on obesity, high serum glucose and total cholesterol levels, and high blood pressure. The occurrence of cancer was identified using Korean National Health Insurance claims data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for age group, smoking status, alcohol intake, and regular exercise. Results: A total of 5937 cases of cancer occurred during a mean follow-up period of 10.4 years. In men with a high-risk metabolic profile, the risk of colon cancer was elevated (HR, 1.40; 95% CI, 1.14 to 1.71). In women, a high-risk metabolic profile was associated with a significantly increased risk of gallbladder and biliary tract cancer (HR, 2.05; 95% CI, 1.24 to 3.42). Non-significantly increased risks were observed in men for pharynx, larynx, rectum, and kidney cancer, and in women for colon, liver, breast, and ovarian cancer. Conclusions: The findings of this study support the previously suggested association between metabolic syndrome and the risk of several cancers. A high-risk metabolic profile may be an important risk factor for colon cancer in Korean men and gallbladder and biliary tract cancer in Korean women. PMID:27255073

  11. Gene expression profiling for targeted cancer treatment.

    PubMed

    Yuryev, Anton

    2015-01-01

    There is certain degree of frustration and discontent in the area of microarray gene expression data analysis of cancer datasets. It arises from the mathematical problem called 'curse of dimensionality,' which is due to the small number of samples available in training sets, used for calculating transcriptional signatures from the large number of differentially expressed (DE) genes, measured by microarrays. The new generation of causal reasoning algorithms can provide solutions to the curse of dimensionality by transforming microarray data into activity of a small number of cancer hallmark pathways. This new approach can make feature space dimensionality optimal for mathematical signature calculations. The author reviews the reasons behind the current frustration with transcriptional signatures derived from DE genes in cancer. He also provides an overview of the novel methods for signature calculations based on differentially variable genes and expression regulators. Furthermore, the authors provide perspectives on causal reasoning algorithms that use prior knowledge about regulatory events described in scientific literature to identify expression regulators responsible for the differential expression observed in cancer samples. The author advocates causal reasoning methods to calculate cancer pathway activity signatures. The current challenge for these algorithms is in ensuring quality of the knowledgebase. Indeed, the development of cancer hallmark pathway collections, together with statistical algorithms to transform activity of expression regulators into pathway activity, are necessary for causal reasoning to be used in cancer research.

  12. Global Profiling Strategies for Mapping Dysregulated Metabolic Pathways in Cancer

    PubMed Central

    Benjamin, Daniel I.; Cravatt, Benjamin F.; Nomura, Daniel K.

    2012-01-01

    Cancer cells possess fundamentally altered metabolism that provides a foundation to support tumorigenicity and malignancy. Our understanding of the biochemical underpinnings of cancer has benefited from the integrated utilization of large-scale profiling platforms (e.g. genomics, proteomics, and metabolomics), which, together, can provide a global assessment of how enzymes and their parent metabolic networks become altered in cancer to fuel tumor growth. This review presents several examples of how these integrated platforms have yielded fundamental insights into dysregulated metabolism in cancer. We will also discuss questions and challenges that must be addressed to more completely describe, and eventually control, the diverse metabolic pathways that support tumorigenesis. PMID:23063552

  13. Updates in Tumor Profiling in Gastrointestinal Cancers.

    PubMed

    Perez, Kimberly; Safran, Howard P

    2015-10-01

    In the last decade there has been a focus on biomarkers that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression of cancers. Characterization of genomes by next-generation sequencing (NGS) has permitted significant advances in gastrointestinal cancer care. These discoveries have fueled the development of novel therapeutics and have laid the groundwork for the development of new treatment strategies. Work in colorectal cancer (CRC) has been in the forefront of these advances. With the continued development of NGS technology and the positive clinical experience in CRC, genome work has begun in esophagogastric, pancreatic, and hepatocellular carcinomas as well.

  14. Terminal care of the child with cancer at home.

    PubMed

    Sirkiä, K; Saarinen, U M; Ahlgren, B; Hovi, L

    1997-10-01

    One hundred paediatric patients with either leukaemia (36%), solid tumours (34%) or brain tumours (30%), treated at the Children's Hospital, University of Helsinki, Finland, died during 1987-92; 70 of them died while in organized terminal care. They were treated at home (60%), in hospital (29%), and partly at both (11%). One or both parents stayed at home to take care of their child. Personnel of the oncologic ward coordinated home care. The purpose of this study was to evaluate the advantages and disadvantages of a terminal care program, with special reference to terminal care at home. Evaluation included retrospective analysis of patients' records, as well as a structured interview with the two parents separately. The quality of life of the children during the terminal period was greatly influenced by their happiness at being at home. Relief of symptoms, particularly pain, was in most instances adequate. Most parents had no complaints to make afterwards. Only some of them complained of having received too little information, too little supervision and support, and insufficient preparation for the death of the child. Thus, the system of terminal care at home proved satisfactory for the child and the whole family in many different respects. For successful home care, the parents need continuous supervision, help and support by well-trained personnel.

  15. Analysis of lipid profile in cancer patients, smokers, and nonsmokers.

    PubMed

    Reddy, A Vikramsimha; Killampalli, Lakshmi Keerthana; Prakash, A Ravi; Naag, Sushma; Sreenath, G; Biraggari, Sunil Kumar

    2016-01-01

    Lipids play an important role in maintaining the cell membrane integrity. Lipid profile is a panel of blood tests that serve as an initial medical screening for abnormalities in lipids and approximate risk for cancer, cardiovascular diseases, pancreatitis, etc., The present study evaluates the alterations in lipid profile in cancer patients, smokers, and nonsmokers and aims to achieve a correlation between them. The study is an in vitro type of cross-sectional study with 25 oral cancer patients, 25 chronic smokers (habit persisting for 15 years or more), and 15 nonsmokers as control group. Blood samples had been collected, and triglycerides (TGs), total cholesterol (TC), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) were analyzed using a lipid profile kit and an autoanalyzer. The results were analyzed using the unpaired t-test and ANOVA test (P < 0.05). There was a significant increase in TC, TG, LDL, and VLDL and decrease in HDL in the smokers group when compared to the controls (P < 0.05). A significant increase in LDL, but a decrease in values of HDL, VLDL, TG, and TC was observed in the cancer patients group when compared to the controls (P < 0.05). There is an inverse relationship between serum lipid profile in smokers and cancer patients. The decrease in lipid profile in cancer patients might be due to their increased utilization of lipids by neoplastic cells in membrane biogenesis. Therefore, a decrease in lipid profile in smokers can be assumed that they might be more prone to develop cancerous conditions.

  16. Analysis of lipid profile in cancer patients, smokers, and nonsmokers

    PubMed Central

    Reddy, A. Vikramsimha; Killampalli, Lakshmi Keerthana; Prakash, A. Ravi; Naag, Sushma; Sreenath, G.; Biraggari, Sunil Kumar

    2016-01-01

    Background: Lipids play an important role in maintaining the cell membrane integrity. Lipid profile is a panel of blood tests that serve as an initial medical screening for abnormalities in lipids and approximate risk for cancer, cardiovascular diseases, pancreatitis, etc., The present study evaluates the alterations in lipid profile in cancer patients, smokers, and nonsmokers and aims to achieve a correlation between them. Materials and Methods: The study is an in vitro type of cross-sectional study with 25 oral cancer patients, 25 chronic smokers (habit persisting for 15 years or more), and 15 nonsmokers as control group. Blood samples had been collected, and triglycerides (TGs), total cholesterol (TC), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) were analyzed using a lipid profile kit and an autoanalyzer. The results were analyzed using the unpaired t-test and ANOVA test (P < 0.05). Results: There was a significant increase in TC, TG, LDL, and VLDL and decrease in HDL in the smokers group when compared to the controls (P < 0.05). A significant increase in LDL, but a decrease in values of HDL, VLDL, TG, and TC was observed in the cancer patients group when compared to the controls (P < 0.05). Conclusion: There is an inverse relationship between serum lipid profile in smokers and cancer patients. The decrease in lipid profile in cancer patients might be due to their increased utilization of lipids by neoplastic cells in membrane biogenesis. Therefore, a decrease in lipid profile in smokers can be assumed that they might be more prone to develop cancerous conditions. PMID:28182070

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

    PubMed Central

    Ahmed, Atif A.; Abedalthagafi, Malak

    2016-01-01

    Although histomorphology has made significant advances into the understanding of cancer etiology, classification and pathogenesis, it is sometimes complicated by morphologic ambiguities, and other shortcomings that necessitate the development of ancillary tests to complement its diagnostic value. A new approach to cancer patient management consists of targeting specific molecules or gene mutations in the cancer genome by inhibitory therapy. Molecular diagnostic tests and genomic profiling methods are increasingly being developed to identify tumor targeted molecular profile that is the basis of targeted therapy. Novel targeted therapy has revolutionized the treatment of gastrointestinal stromal tumor, renal cell carcinoma and other cancers that were previously difficult to treat with standard chemotherapy. In this review, we discuss the role of histomorphology in cancer diagnosis and management and the rising role of molecular profiling in targeted therapy. Molecular profiling in certain diagnostic and therapeutic difficulties may provide a practical and useful complement to histomorphology and opens new avenues for targeted therapy and alternative methods of cancer patient management. PMID:27509178

  18. Using spiral intensity profile to quantify head and neck cancer

    PubMed Central

    Kong, Koon Y.; Shanna, Yachna; Raza, S. Hussain; Chen, Zhuo (Georgia); Muller, Susan; Wang, May D.

    2016-01-01

    During the analysis of microscopy images, researchers locate regions of interest (ROI) and extract relevant information within it. Identifying the ROI is mostly done manually and subjectively by pathologists. Computer algorithms could help in reducing their workload and improve reproducibility. In particular, we want to assess the validity of the folic acid receptor as a biomarker for head and neck cancer. We are only interested in folic acid receptors appearing in cancerous tissue. Therefore, the first step is to segment images into cancerous and noncancerous regions. We propose to use a spiral intensity profile for segmentation of light microscopy images. Many algorithms identify objects in an image by considering pixel intensity and spatial information separately. Our algorithm integrates intensity and spatial information by considering the change, or profile, of pixel intensity in a spiral fashion. Using a spiral intensity profile can also perform segmentation at different scales from cancer regions to nuclei cluster to individual nuclei. We compared our algorithm with manually segmented image and obtained a specificity of 83.7% and sensitivity of 61.1%. Spiral intensity profiles can be used as a feature to improve other segmentation algorithms. Segmentation of cancerous images at different scales allows effective quantification of folic acid receptor inside cancerous regions, nuclei clusters, or individual cells.

  19. Development of the Cancer Survivor Profile

    DTIC Science & Technology

    2014-05-09

    behaviors (e.g., alcohol consumption ≥ 6 g/day, poor nutrition , lack of physical activity) have been positively associated with an elevated risk for...and physical effects of cancer, as well as a focus on nutrition and exercise (196; 222). However, current survivorship care planning methods (e.g...et al. 2006. Dietary fat reduction and breast cancer outcome: Interim efficacy results from the women’s intervention nutrition study. Journal of the

  20. Lung Cancer Risk from Radon in Marcellus Shale Gas in Northeast U.S. Homes.

    PubMed

    Mitchell, Austin L; Griffin, W Michael; Casman, Elizabeth A

    2016-11-01

    The amount of radon in natural gas varies with its source. Little has been published about the radon from shale gas to date, making estimates of its impact on radon-induced lung cancer speculative. We measured radon in natural gas pipelines carrying gas from the Marcellus Shale in Pennsylvania and West Virginia. Radon concentrations ranged from 1,520 to 2,750 Bq/m(3) (41-74 pCi/L), and the throughput-weighted average was 1,983 Bq/m(3) (54 pCi/L). Potential radon exposure due to the use of Marcellus Shale gas for cooking and space heating using vent-free heaters or gas ranges in northeastern U.S. homes and apartments was assessed. Though the measured radon concentrations are higher than what has been previously reported, it is unlikely that exposure from natural gas cooking would exceed 1.2 Bq/m(3) (<1% of the U.S. Environmental Protection Agency's action level). Using worst-case assumptions, we estimate the excess lifetime (70 years) lung cancer risk associated with cooking to be 1.8×10(-4) (interval spanning 95% of simulation results: 8.5×10(-5) , 3.4×10(-4) ). The risk profile for supplemental heating with unvented gas appliances is similar. Individuals using unvented gas appliances to provide primary heating may face lifetime risks as high as 3.9×10(-3) . Under current housing stock and gas consumption assumptions, expected levels of residential radon exposure due to unvented combustion of Marcellus Shale natural gas in the Northeast United States do not result in a detectable change in the lung cancer death rates.

  1. Pattern of drug use by advanced cancer patients followed at home.

    PubMed

    Mercadante, S; Fulfaro, F; Casuccio, A

    2001-01-01

    The aim of this study was to document the drugs most commonly prescribed to control symptoms in advanced cancer patients being followed at home. We analyzed data for 128 patients admitted to a home palliative care program from January 1993 to January 1995. All patients were followed at home until death by a team consisting of doctors and nurses, and were given two or three medical examinations a week. The most frequently prescribed drugs were analgesics and drugs commonly used to prevent NSAID-induced gastric toxicity. Slow-release morphine was the analgesic used most often. Most patients received more than four drugs. Younger people received morphine more often than did older patients. Drug monitoring is a useful audit tool for verifying the quality and quantity of drugs prescribed for advanced cancer patients being followed at home. Pharmacological usage should be reviewed periodically and should reflect evidence-based practice.

  2. Objective Diagnosis of Cervical Cancer by Tissue Protein Profile Analysis

    NASA Astrophysics Data System (ADS)

    Patil, Ajeetkumar; Bhat, Sujatha; Rai, Lavanya; Kartha, V. B.; Chidangil, Santhosh

    2011-07-01

    Protein profiles of homogenized normal cervical tissue samples from hysterectomy subjects and cancerous cervical tissues from biopsy samples collected from patients with different stages of cervical cancer were recorded using High Performance Liquid Chromatography coupled with Laser Induced Fluorescence (HPLC-LIF). The Protein profiles were subjected to Principle Component Analysis to derive statistically significant parameters. Diagnosis of sample types were carried out by matching three parameters—scores of factors, squared residuals, and Mahalanobis Distance. ROC and Youden's Index curves for calibration standards were used for objective estimation of the optimum threshold for decision making and performance.

  3. Smoke-free Home Rules | Cancer Trends Progress Report

    Cancer.gov

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  4. Smoke-free Home Rules | Cancer Trends Progress Report

    Cancer.gov

    The Cancer Trends Progress Report, first issued in 2001, summarizes our nation's advances against cancer in relation to Healthy People targets set forth by the Department of Health and Human Services.

  5. Profile of olaparib in the treatment of advanced ovarian cancer.

    PubMed

    Chase, Dana M; Patel, Shreya; Shields, Kristin

    2016-01-01

    Olaparib is a poly(ADP-ribose) polymerase inhibitor that received accelerated approval from the US Food and Drug Administration as monotherapy for patients with germline BRCA mutations and ovarian cancer treated with three or more prior lines of chemotherapy. This article summarizes the mechanism of poly(ADP-ribose) polymerase inhibition, therapeutic profile and uses of olaparib, and current and ongoing literature pertaining to olaparib in advanced ovarian cancer.

  6. Quantitative DNA Methylation Profiling in Cancer.

    PubMed

    Ammerpohl, Ole; Haake, Andrea; Kolarova, Julia; Siebert, Reiner

    2016-01-01

    Epigenetic mechanisms including DNA methylation are fundamental for the regulation of gene expression. Epigenetic alterations can lead to the development and the evolution of malignant tumors as well as the emergence of phenotypically different cancer cells or metastasis from one single tumor cell. Here we describe bisulfite pyrosequencing, a technology to perform quantitative DNA methylation analyses, to detect aberrant DNA methylation in malignant tumors.

  7. Quality of life in Chinese home-based advanced cancer patients: does awareness of cancer diagnosis matter?

    PubMed

    Fan, Xiaoping; Huang, Hua; Luo, Qiong; Zhou, Jiying; Tan, Ge; Yong, Na

    2011-10-01

    The aim of this study was to assess the quality of life (QOL) of Chinese home-based advanced-stage cancer patients and to evaluate the association between the disclosure of cancer diagnosis and QOL. An interview-based survey was conducted from December 2009 to June 2010 in the home-based hospice of the First Affiliated Hospital of Chongqing Medical University, China. The principal finding of this study demonstrated that patients who did not have knowledge of their diagnosis exhibited better physical and emotional QOL compared with those who had knowledge of their diagnosis.

  8. Gene expression profiling in bladder cancer identifies potential therapeutic targets

    PubMed Central

    Hussain, Syed A.; Palmer, Daniel H.; Syn, Wing-Kin; Sacco, Joseph J.; Greensmith, Richard M.D.; Elmetwali, Taha; Aachi, Vijay; Lloyd, Bryony H.; Jithesh, Puthen V.; Arrand, John; Barton, Darren; Ansari, Jawaher; Sibson, D. Ross; James, Nicholas D.

    2017-01-01

    Despite advances in management, bladder cancer remains a major cause of cancer related complications. Characterisation of gene expression patterns in bladder cancer allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. Between 2004 and 2005, cystoscopic bladder biopsies were obtained from 19 patients and 11 controls. These were subjected to whole transcript-based microarray analysis. Unsupervised hierarchical clustering was used to identify samples with similar expression profiles. Hypergeometric analysis was used to identify canonical pathways and curated networks having statistically significant enrichment of differentially expressed genes. Osteopontin (OPN) expression was validated by immunohistochemistry. Hierarchical clustering defined signatures, which differentiated between cancer and healthy tissue, muscle-invasive or non-muscle invasive cancer and healthy tissue, grade 1 and grade 3. Pathways associated with cell cycle and proliferation were markedly upregulated in muscle-invasive and grade 3 cancers. Genes associated with the classical complement pathway were downregulated in non-muscle invasive cancer. Osteopontin was markedly overexpressed in invasive cancer compared to healthy tissue. The present study contributes to a growing body of work on gene expression signatures in bladder cancer. The data support an important role for osteopontin in bladder cancer, and identify several pathways worthy of further investigation. PMID:28259975

  9. Building America Top Innovations 2013 Profile – Zero Energy-Ready Single-Family Homes

    SciTech Connect

    none,

    2013-09-01

    Building homes that are zero energy-ready is a goal of the U.S. Department of Energy’s Building America program and one embodied in Building America’s premier home certification program, the Challenge Home program. This case study describes several examples of successful zero energy-ready home projects completed by Building America teams and partner builders.

  10. Genetic tumor profiling and genetically targeted cancer therapy.

    PubMed

    Goetsch, Cathleen M

    2011-02-01

    To discuss how understanding and manipulation of tumor genetics information and technology shapes cancer care today and what changes might be expected in the near future. Published articles, web resources, clinical practice. Advances in our understanding of genes and their regulation provide a promise of more personalized cancer care, allowing selection of the most safe and effective therapy in an individual situation. Rapid progress in the technology of tumor profiling and targeted cancer therapies challenges nurses to keep up-to-date to provide quality patient education and care. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Biliary Tract Cancer: Epidemiology, Radiotherapy, and Molecular Profiling.

    PubMed

    Bridgewater, John A; Goodman, Karyn A; Kalyan, Aparna; Mulcahy, Mary F

    2016-01-01

    Biliary tract cancer, or cholangiocarcinoma, arises from the biliary epithelium of the small ducts in the periphery of the liver (intrahepatic) and the main ducts of the hilum (extrahepatic), extending into the gallbladder. The incidence and epidemiology of biliary tract cancer are fluid and complex. It is shown that intrahepatic cholangiocarcinoma is on the rise in the Western world, and gallbladder cancer is on the decline. Radiation therapy has emerged as an important component of adjuvant therapy for resected disease and definitive therapy for locally advanced disease. The emerging sophisticated techniques of imaging tumors and conformal dose delivery are expanding the indications for radiotherapy in the management of bile duct tumors. As we understand more about the molecular pathways driving biliary tract cancers, targeted therapies are at the forefront of new therapeutic combinations. Understanding the gene expression profile and mutational burden in biliary tract cancer allows us to better discern the pathogenesis and identify promising new developmental therapeutic targets.

  12. T-lymphocyte homing: an underappreciated yet critical hurdle for successful cancer immunotherapy.

    PubMed

    Sackstein, Robert; Schatton, Tobias; Barthel, Steven R

    2017-03-27

    Advances in cancer immunotherapy have offered new hope for patients with metastatic disease. This unfolding success story has been exemplified by a growing arsenal of novel immunotherapeutics, including blocking antibodies targeting immune checkpoint pathways, cancer vaccines, and adoptive cell therapy (ACT). Nonetheless, clinical benefit remains highly variable and patient-specific, in part, because all immunotherapeutic regimens vitally hinge on the capacity of endogenous and/or adoptively transferred T-effector (Teff) cells, including chimeric antigen receptor (CAR) T cells, to home efficiently into tumor target tissue. Thus, defects intrinsic to the multi-step T-cell homing cascade have become an obvious, though significantly underappreciated contributor to immunotherapy resistance. Conspicuous have been low intralesional frequencies of tumor-infiltrating T-lymphocytes (TILs) below clinically beneficial threshold levels, and peripheral rather than deep lesional TIL infiltration. Therefore, a Teff cell 'homing deficit' may arguably represent a dominant factor responsible for ineffective immunotherapeutic outcomes, as tumors resistant to immune-targeted killing thrive in such permissive, immune-vacuous microenvironments. Fortunately, emerging data is shedding light into the diverse mechanisms of immune escape by which tumors restrict Teff cell trafficking and lesional penetrance. In this review, we scrutinize evolving knowledge on the molecular determinants of Teff cell navigation into tumors. By integrating recently described, though sporadic information of pivotal adhesive and chemokine homing signatures within the tumor microenvironment with better established paradigms of T-cell trafficking under homeostatic or infectious disease scenarios, we seek to refine currently incomplete models of Teff cell entry into tumor tissue. We further summarize how cancers thwart homing to escape immune-mediated destruction and raise awareness of the potential impact of immune

  13. Molecular profiling of male breast cancer - lost in translation?

    PubMed

    Johansson, Ida; Killander, Fredrika; Linderholm, Barbro; Hedenfalk, Ingrid

    2014-08-01

    Breast cancer is the most common cancer form in women and it has been extensively studied on the molecular level. Male breast cancer (MBC), on the other hand, is rare and has not been thoroughly investigated in terms of transcriptional profiles or genomic aberrations. Most of our understanding of MBC has therefore been extrapolated from knowledge of female breast cancer. Although differences in addition to similarities with female breast cancer have been reported, the same prognostic and predictive markers are used to determine optimal management strategies for both men and women diagnosed with breast cancer. This review is focused on prognosis for MBC patients, prognostic and predictive factors and molecular subgrouping; comparisons are made with female breast cancer. Information was collected from relevant literature on both male and female breast cancer from the MEDLINE database between 1992 and 2014. MBC is a heterogeneous disease, and on the molecular level many differences compared to female breast cancer have recently been revealed. Two distinct subgroups of MBC, luminal M1 and luminal M2, have been identified which differ from the well-established intrinsic subtypes of breast cancer in women. These novel subgroups of breast cancer therefore appear unique to MBC. Furthermore, several studies report inferior survival for men diagnosed with breast cancer compared to women. New promising prognostic biomarkers for MBC (e.g. NAT1) deserving further attention are reviewed. Further prospective studies aimed at validating the novel subgroups and recently proposed biomarkers for MBC are warranted to provide the basis for optimal patient management in this era of personalized medicine. This article is part of a Directed Issue entitled: Rare Cancers. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. The Profile and Incidence of Cancer in Down Syndrome

    ERIC Educational Resources Information Center

    Sullivan, S. G.; Hussain, R.; Glasson, E. J.; Bittles, A. H.

    2007-01-01

    Background: Down syndrome is one of the commonest causes of intellectual disability. As life expectancy improves with early and more intensive surgical and medical treatments, people with the disorder are more likely to exhibit classic morbidity and mortality patterns and be diagnosed with diseases such as cancer. Methods: A profile of cancer…

  15. Sun Protection Motivational Stages and Behavior: Skin Cancer Risk Profiles

    ERIC Educational Resources Information Center

    Pagoto, Sherry L.; McChargue, Dennis E.; Schneider, Kristin; Cook, Jessica Werth

    2004-01-01

    Objective: To create skin cancer risk profiles that could be used to predict sun protection among Midwest beachgoers. Method: Cluster analysis was used with study participants (N=239), who provided information about sun protection motivation and behavior, perceived risk, burn potential, and tan importance. Participants were clustered according to…

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

    PubMed Central

    Zardavas, Dimitrios; Piccart-Gebhart, Martine

    2016-01-01

    The implementation of molecular profiling technologies in oncology deepens our knowledge for the molecular landscapes of cancer diagnoses, identifying aberrations that could be linked with specific therapeutic vulnerabilities. In particular, there is an increasing list of molecularly targeted anticancer agents undergoing clinical development that aim to block specific molecular aberrations. This leads to a paradigm shift, with an increasing list of specific aberrations dictating the treatment of patients with cancer. This paradigm shift impacts the field of clinical trials, since the classical approach of having clinico-pathological disease characteristics dictating the patients' enrolment in oncology trials shifts towards the implementation of molecular profiling as pre-screening step. In order to facilitate the successful clinical development of these new anticancer drugs within specific molecular niches of cancer diagnoses, there have been developed new, innovative trial designs that could be classified as follows: i) longitudinal cohort studies that implement (or not) "nested" downstream trials, 2) studies that assess the clinical utility of molecular profiling, 3) "master" protocol trials, iv) "basket" trials, v) trials following an adaptive design. In the present article, we review these innovative study designs, providing representative examples from each category and we discuss the challenges that still need to be addressed in this era of new generation oncology trials implementing molecular profiling. Emphasis is put on the field of breast cancer clinical trials. PMID:27458530

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

    PubMed

    Zardavas, Dimitrios; Piccart-Gebhart, Martine

    2016-06-01

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

  18. Sun Protection Motivational Stages and Behavior: Skin Cancer Risk Profiles

    ERIC Educational Resources Information Center

    Pagoto, Sherry L.; McChargue, Dennis E.; Schneider, Kristin; Cook, Jessica Werth

    2004-01-01

    Objective: To create skin cancer risk profiles that could be used to predict sun protection among Midwest beachgoers. Method: Cluster analysis was used with study participants (N=239), who provided information about sun protection motivation and behavior, perceived risk, burn potential, and tan importance. Participants were clustered according to…

  19. The Child Health and Illness Profile--Adolescent Edition: Assessing Well-Being in Group Homes or Institutions.

    ERIC Educational Resources Information Center

    Altshuler, Sandra J.; Poertner, John

    2002-01-01

    The Child Health and Illness Profile--Adolescent Edition (CHIP-AE) was administered to 63 adolescents in group settings. Domains studied were satisfaction, resilience, risk, achievement, and disorders. Compared to a normed group, youth in group homes or institutions felt physically healthy and safe and were resilient. Of concern were low…

  20. Elementary School ELLs' Reading Skill Profiles Using Cognitive Diagnosis Modeling: Roles of Length of Residence and Home Language Environment

    ERIC Educational Resources Information Center

    Jang, Eunice Eunhee; Dunlop, Maggie; Wagner, Maryam; Kim, Youn-Hee; Gu, Zhimei

    2013-01-01

    The study examined differences in reading achievement and mastery skill development among Grade-6 students with different language background profiles, using cognitive diagnosis modeling applied to large-scale provincial reading test performance data. Our analyses revealed that students residing in various home language environments show different…

  1. Elementary School ELLs' Reading Skill Profiles Using Cognitive Diagnosis Modeling: Roles of Length of Residence and Home Language Environment

    ERIC Educational Resources Information Center

    Jang, Eunice Eunhee; Dunlop, Maggie; Wagner, Maryam; Kim, Youn-Hee; Gu, Zhimei

    2013-01-01

    The study examined differences in reading achievement and mastery skill development among Grade-6 students with different language background profiles, using cognitive diagnosis modeling applied to large-scale provincial reading test performance data. Our analyses revealed that students residing in various home language environments show different…

  2. The Child Health and Illness Profile--Adolescent Edition: Assessing Well-Being in Group Homes or Institutions.

    ERIC Educational Resources Information Center

    Altshuler, Sandra J.; Poertner, John

    2002-01-01

    The Child Health and Illness Profile--Adolescent Edition (CHIP-AE) was administered to 63 adolescents in group settings. Domains studied were satisfaction, resilience, risk, achievement, and disorders. Compared to a normed group, youth in group homes or institutions felt physically healthy and safe and were resilient. Of concern were low…

  3. Large-scale profiling of metabolic dysregulation in ovarian cancer.

    PubMed

    Ke, Chaofu; Hou, Yan; Zhang, Haiyu; Fan, Lijun; Ge, Tingting; Guo, Bing; Zhang, Fan; Yang, Kai; Wang, Jingtao; Lou, Ge; Li, Kang

    2015-02-01

    Ovarian cancer is the leading cause of death in gynecologic malignancies. Profiling of endogenous metabolites has potential to identify changes caused by cancer and provide inspiring insights into cancer metabolism. To systematically investigate ovarian cancer metabolism, we performed metabolic profiling of 448 plasma samples related to epithelial ovarian cancer (EOC) based on ultra-performance liquid chromatography mass spectrometry in both positive and negative modes. These unbiased metabolomic profiles could well distinguish EOC from benign ovarian tumor (BOT) and uterine fibroid (UF). Fifty-three metabolites were identified as specific biomarkers for EOC, and this is the first report of piperine, 3-indolepropionic acid, 5-hydroxyindoleacetaldehyde and hydroxyphenyllactate as metabolic biomarkers of EOC. The AUC values of these metabolites for discriminating EOC from BOT/UF and early-stage EOC from BOT/UF were 0.9100/0.9428 and 0.8385/0.8624, respectively. Meanwhile, our metabolites were able to distinguish early-stage EOC from late-stage EOC with an AUC of 0.8801. Importantly, analysis of dysregulated metabolic pathways extends our current understanding of EOC metabolism. Metabolic pathways in EOC patients are mainly characterized by abnormal phospholipid metabolism, altered l-tryptophan catabolism, aggressive fatty acid β-oxidation and aberrant metabolism of piperidine derivatives. Together, these metabolic pathways provide a foundation to support cancer development and progression. In conclusion, our large-scale plasma metabolomics study yielded fundamental insights into dysregulated metabolism in ovarian cancer, which could facilitate clinical diagnosis, therapy, prognosis and shed new lights on ovarian cancer pathogenesis.

  4. Home administration of maintenance pemetrexed for patients with advanced non-squamous non-small cell lung cancer: rationale, practicalities and phase II feasibility study design

    PubMed Central

    2013-01-01

    Background Home-based care in oncology is mainly reserved for patients at the end of life. Regulations regarding home delivery of cytotoxics differ across Europe, with a notable lack of practice guidelines in most countries. This has led to a lack of data addressing the feasibility of home-based administration of cytotoxic chemotherapy. In advanced non-squamous non-small cell lung cancer, pemetrexed is approved as maintenance therapy after first-line chemotherapy. In this setting, patients have the potential to be treated long-term with maintenance therapy, which, in the absence of unacceptable toxicity, is continued until disease progression. The favourable safety profile of pemetrexed and the ease of its administration by 10-minute intravenous infusion every 3 weeks make this drug a suitable candidate for administration in a home setting. Methods Literature and regulations relevant to the home-based delivery of cytotoxic therapy were reviewed, and a phase II feasibility study of home administration of pemetrexed maintenance therapy was designed. At least 50 patients with advanced non-squamous non-small cell lung cancer, Eastern Cooperative Oncology Group performance status 0–1 and no progressive disease after four cycles of platinum-based first-line therapy are required to allow investigation of the feasibility of home-based administration of pemetrexed maintenance therapy (500 mg/m2 every 3 weeks until progressive disease or unacceptable toxicity). Feasibility is being assessed as adherence to the home-based administration process (primary endpoint), patient safety, impact on patients’ quality of life, patient and physician satisfaction with home care, and healthcare resource use and costs. Enrolment of patients from the UK and Sweden, where home-based care is relatively well developed, commenced in December 2011. Discussion This feasibility study addresses an important aspect of maintenance therapy, that is, patient comfort during protracted home

  5. Genomic profiling of inflammatory breast cancer: a review.

    PubMed

    Bertucci, François; Finetti, Pascal; Vermeulen, Peter; Van Dam, Peter; Dirix, Luc; Birnbaum, Daniel; Viens, Patrice; Van Laere, Steven

    2014-10-01

    Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. Despite efforts in the past decade to delineate the molecular biology of IBC by applying high-throughput molecular profiling technologies to clinical samples, IBC remains insufficiently characterized. The reasons for that include limited sizes of the study population, heterogeneity with respect to the composition of the IBC and non-IBC control groups and technological differences across studies. In 2008, the World IBC Consortium was founded to foster collaboration between research groups focusing on IBC. One of the initial projects was to redefine the molecular profile of IBC using an unprecedented number of samples and search for gene signatures associated with survival and response to neo-adjuvant chemotherapy. Here, we provide an overview of all the molecular profiling studies that have been performed on IBC clinical samples to date.

  6. Molecular profiling of human cancer: new opportunities.

    PubMed

    Englert, C R; Petricoin, E F; Krizman, D B; Emmert-Buck, M R

    1999-12-01

    The Human Genome Project will be completed in the near future, providing new opportunities for researchers to better understand human biology. In order to maximize the value of the genetic data, high-throughput molecular analyses will become an essential experimental methodology, allowing global views of gene expression to be produced and examined. As an example, this approach will permit investigators studying cancer to comprehensively examine the genes and gene products whose alterations underlie tumor development and progression. This information will be essential in determining the fundamental causes of human neoplasms as well as having immediate practical value in the development of clinically useful diagnostic markers and therapeutic targets.

  7. [Creative activities in home care for terminally-ill cancer patients at a rural municipal hospital].

    PubMed

    Miyao, Y; Tonouchi, A; Yokoyama, H

    1999-12-01

    Karuizawa Hospital is a rural, small town municipal hospital with 60 beds, located in Nagano Prefecture in central Japan. The terminal stages of patients who were treated in our department of surgery but later died of cancer are reviewed. In the five year period extending from April, 1994 through March, 1999 sixty patients died from cancer. Of them, 34 people died in their own home and 26 in our hospital. The annual ratio of patients who died at home to those who died in the hospital are analyzed, as well as whether these ratios differed according to the location of the patient's cancer. The identity of the patients' main home caregiver was sought, as well as how many days the patients resided at home until they passed away, and how frequently doctors or nurses visited their home. Some of the doctors' attempts to gain informed consent are described. Based on the findings, the authors recommend an end to the practice of first revealing the name and details of a patient's disease to his/her family. It was also found that documented information is useful in order to promote smooth relationships among patients, family members, and the doctor.

  8. Metastatic Cancer of Cowper's Gland: A Rare Cancer Managed Successfully by Molecular Profiling

    PubMed Central

    Myers, Charles E.; Gatalica, Zoran; Spinelli, Anthony; Castro, Michael; Linden, Erica; Sartor, Oliver; Sargent, Mathew

    2014-01-01

    Cancer of Cowper's gland is a very rare cancer. This case represents the 9th case in the medical literature. As such, there are no phase II or phase III trials to guide treatment. In this article, we report the successful treatment of a patient over a 7-year period guided solely by molecular profiling. Through multiple cycles to treatment, the cancer was controlled using drugs targeting c-kit, as the cancer steadily increased the expression of c-kit. This report also documents the use of a novel drug combination based on sunitinib that was well tolerated and may warrant testing in other c-kit-dependent cancers. PMID:24575017

  9. Home literacy environment profiles of children with language impairment: associations with caregiver- and child-specific factors.

    PubMed

    Tambyraja, Sherine R; Schmitt, Mary Beth; Farquharson, Kelly; Justice, Laura M

    2017-03-01

    Numerous studies suggest a positive relationship between the home literacy environment (HLE) and children's language and literacy skills, yet very little research has focused on the HLE of children with language impairment (LI). Children with LI are at risk for reading difficulties; thus, understanding the nature and frequency of their home literacy interactions is warranted. To identify unique HLE profiles within a large sample of children with LI, and to determine relevant caregiver- and child-specific factors that predict children's profile membership. Participants were 195 kindergarten and first-grade children with LI who were receiving school-based language therapy. Caregivers completed a comprehensive questionnaire regarding their child's HLE, and the extent to which their child engaged in shared book reading, were taught about letters, initiated or asked to be read to, and chose to read independently. Caregivers also answered questions regarding the highest level of maternal education, caregiver history of reading difficulties, and caregiver reading habits. Children completed a language and literacy battery in the fall of their academic year. Latent profile analyses indicated a three-profile solution, representing high, average and low frequency of the selected HLE indicators. Multinomial regression further revealed that caregivers' own reading habits influenced children's profile membership, as did child age and language abilities. These results highlight the considerable variability in the frequency of home literacy interactions of children with LI. Future work examining relations between familial reading practices and literacy outcomes for children with LI is warranted. © 2016 Royal College of Speech and Language Therapists.

  10. Cancer Cell Dissemination and Homing to the Bone Marrow in a Zebrafish Model.

    PubMed

    Sacco, Antonio; Roccaro, Aldo M; Ma, Dongdong; Shi, Jiantao; Mishima, Yuji; Moschetta, Michele; Chiarini, Marco; Munshi, Nikhil; Handin, Robert I; Ghobrial, Irene M

    2016-01-15

    Advancement of many solid tumors and hematologic malignancies is frequently characterized by dissemination and homing of cancer cells to the bone marrow (BM). Methods to quantitatively characterize these key steps of the metastatic cascade in mammalian models are currently limited and do not offer opportunities to perform rapid, large-scale genomic, or drug screening. Because of their optical clarity, we used zebrafish to develop an in vivo model of cancer cell dissemination and homing to the BM. We performed intracardiac injection of multiple myeloma (MM) cells derived from human BM or cell lines and monitored their migration to the caudal hematopoietic tissue (CHT), the region where hematopoiesis occurs in the zebrafish embryo, which recapitulates a BM-like niche. Transcriptomic analyses confirmed that MM cells homing to the CHT displayed gene-expression differences compared with MM cells outside of the CHT, including significant enrichment for genes known to regulate interleukin-6 (IL6) signaling, cell adhesion, and angiogenesis. Collectively, our findings point to the zebrafish as a valuable model in which to study cancer cell homing to the hematopoietic niche and to establish a screening platform for the identification of factors and mechanisms contributing to the early steps of bone metastasis. ©2016 American Association for Cancer Research.

  11. Changes in profiles of airborne fungi in flooded homes in southern Taiwan after Typhoon Morakot.

    PubMed

    Hsu, Nai-Yun; Chen, Pei-Yu; Chang, Hsin-Wen; Su, Huey-Jen

    2011-04-01

    In August 2009, the historic Typhoon Morakot brought extreme rainfall and resulted in flooding which spread throughout southern Taiwan. This study compared the difference between fungal concentrations before and after the disaster in selected homes of the Tainan metropolitan area, which were hit hardest by the catastrophe. A group of 83 households available from a prior cohort established with random sampling out of a regional population in southern Taiwan was contacted successfully by telephone. Twenty-five of these reported to have suffered from floods of various degrees at this time. Around 2 weeks after the event, at which time most of the remedial process had been completed by self-efforts and public health endeavours, 14 of these 25 (56%) agreed to participate in measurements of the airborne microbial concentrations. The averages (standard deviation) of the total culturable fungal concentrations in children's bedrooms and flooded rooms were 18,181 (25,854) colony-forming units per cubic metre (CFU/m(3)) and 13,440 (11,033) CFU/m(3), respectively. The airborne fungal spore levels in the 2 above-mentioned indoor sites were 221,536 (169,640) spores/m(3) and 201,582 (137,091) spores/m(3), respectively. The average indoor/outdoor ratios in the children's bedrooms were 4.2 for culturable fungi and 1.4 for fungal spores. These values were higher than the respective values measured in the same homes during the previous year: 1.1 and 0.6. In terms of the specific fungal profile, the percentages of Aspergillus spp. increased significantly in both the indoor and outdoor environments after the event. To this date, this study is among the limited research that has been conducted to quantitatively demonstrate that fungal manifestation is likely to persist in flooded homes even after seemingly robust remedial measures have been put into place. Studies to examine the potential health implications and effectiveness of better remedial technology remain much needed.

  12. Cancer risks from exposure to radon in homes.

    PubMed Central

    Axelson, O

    1995-01-01

    Exposure to radon and its decay products in mines is a well recognized risk of lung cancer in miners. A large number of epidemiologic studies from various countries are quite consistent in this respect even it the magnitude of the risk differs according to exposure levels. Indoor radon became a concern in the 1970s and about a dozen studies have been conducted since 1979, mainly of the case-control design. From first being of a simple pilot character, the designs have become increasingly sophisticated, especially with regard to exposure assessment. Crude exposure estimates based on type of house, building material and geological features have been supplemented or replaced by quite extensive measurements. Still, exposure assessment remains a difficult and uncertain issue in these studies, most of which indicate a lung cancer risk from indoor radon. Also a recent large scale study has confirmed a lung cancer risk from indoor radon. More recently there are also some studies, mainly of the correlation type, suggesting other cancers also to be related to indoor radon, especially leukemia, kidney cancer, and malignant melanoma, and some other cancers as well. The data are less consistent and much more uncertain than for indoor radon and lung cancer, however; and there is no clear support from studies of miners in this respect. PMID:7614945

  13. Marching to the Beat of Their Own Drum! A Profile of Home Education Research.

    ERIC Educational Resources Information Center

    Ray, Brian D.

    This publication summarizes recent research findings on home education. In particular, the booklet examines the movement's historical background; reasons why parents choose to home school their children; home-schooling characteristics, practices, and outcomes; and the impact on children's social development. Findings indicate that the…

  14. Young Children's Internet Use at Home and School: Patterns and Profiles

    ERIC Educational Resources Information Center

    Johnson, Genevieve Marie

    2010-01-01

    Thirty-eight children in first and second grade completed a 10-item rating scale on Internet use at home and school. Results suggested that, in general, more children used the Internet at school than at home but home-based use was more often perceived as enjoyable. Three patterns of Internet use emerged suggesting three types of young users:…

  15. Young Children's Internet Use at Home and School: Patterns and Profiles

    ERIC Educational Resources Information Center

    Johnson, Genevieve Marie

    2010-01-01

    Thirty-eight children in first and second grade completed a 10-item rating scale on Internet use at home and school. Results suggested that, in general, more children used the Internet at school than at home but home-based use was more often perceived as enjoyable. Three patterns of Internet use emerged suggesting three types of young users:…

  16. Cancer RNA-Seq Nexus: a database of phenotype-specific transcriptome profiling in cancer cells.

    PubMed

    Li, Jian-Rong; Sun, Chuan-Hu; Li, Wenyuan; Chao, Rou-Fang; Huang, Chieh-Chen; Zhou, Xianghong Jasmine; Liu, Chun-Chi

    2016-01-04

    The genome-wide transcriptome profiling of cancerous and normal tissue samples can provide insights into the molecular mechanisms of cancer initiation and progression. RNA Sequencing (RNA-Seq) is a revolutionary tool that has been used extensively in cancer research. However, no existing RNA-Seq database provides all of the following features: (i) large-scale and comprehensive data archives and analyses, including coding-transcript profiling, long non-coding RNA (lncRNA) profiling and coexpression networks; (ii) phenotype-oriented data organization and searching and (iii) the visualization of expression profiles, differential expression and regulatory networks. We have constructed the first public database that meets these criteria, the Cancer RNA-Seq Nexus (CRN, http://syslab4.nchu.edu.tw/CRN). CRN has a user-friendly web interface designed to facilitate cancer research and personalized medicine. It is an open resource for intuitive data exploration, providing coding-transcript/lncRNA expression profiles to support researchers generating new hypotheses in cancer research and personalized medicine.

  17. Characterisation and protein expression profiling of annexins in colorectal cancer.

    PubMed

    Duncan, R; Carpenter, B; Main, L C; Telfer, C; Murray, G I

    2008-01-29

    The annexins are family of calcium-regulated phospholipid-binding proteins with diverse roles in cell biology. Individual annexins have been implicated in tumour development and progression, and in this investigation a range of annexins have been studied in colorectal cancer. Annexins A1, A2, A4 and A11 were identified by comparative proteomic analysis to be overexpressed in colorectal cancer. Annexins A1, A2, A4 and A11 were further studied by immunohistochemistry with a colorectal cancer tissue microarray containing primary and metastatic colorectal cancer and also normal colon. There was significant increase in expression in annexins A1 (P=0.01), A2 (P<0.001), A4 (P<0.001) and A11 (P<0.001) in primary tumours compared with normal colon. There was increasing expression of annexins A2 (P=0.001), A4 (P=0.03) and A11 (P=0.006) with increasing tumour stage. An annexin expression profile was identified by k-means cluster analysis, and the annexin profile was associated with tumour stage (P=0.01) and also patient survival. Patients in annexin cluster group 1 (low annexin expression) had a better survival (log rank=5.33, P=0.02) than patients in cluster group 2 (high annexins A4 and A11 expression). In conclusion, this study has shown that individual annexins are present in colorectal cancer, specific annexins are overexpressed in colorectal cancer and the annexin expression profile is associated with survival.

  18. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is... Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this...

  19. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is... Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this...

  20. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is... Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this...

  1. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is... Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this...

  2. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is... Profiling Test System for Breast Cancer Prognosis.” See § 866.1(e) for the availability of this...

  3. Novel Magnetic Resonance Detection and Profiling of Ovarian Cancer Across Specimens

    DTIC Science & Technology

    2012-10-01

    Breast Cancer Display Both Epithelial and Mesenchymal Markers. Mol. Cancer Res. 2011, 9, 997–1007. 11. Attard, G.; de Bono, J. S. Utilizing Circulating...Profiling of Ovarian Cancer Across Specimens PRINCIPAL INVESTIGATOR: Ralph Weissleder, MD, PhD...September 2011–29 September 2012 4. TITLE AND SUBTITLE Novel Magnetic Resonance Detection and Profiling of Ovarian Cancer Across Specimens 5a. CONTRACT

  4. [Breast cancer in Morocco: phenotypic profile of tumors].

    PubMed

    Khalil, Ahmadaye Ibrahim; Bendahhou, Karima; Mestaghanmi, Houriya; Saile, Rachid; Benider, Abdellatif

    2016-01-01

    Breast cancer is most common in women and it is among the leading causes of cancer related deaths. The curability of this type of tumor is increasing thanks to screening programs and treatment advances which have certainly enhanced patient survival. But challenges remain, particularly in respect of phenotypic instability of cancer cells. The aim of this study was to analyse the phenotypic profile of breast cancer in patients treated at Mohammed VI Cancer Treatment Center over the years 2013-2014. We conducted a cross-sectional study over a two-year period, including the cases of breast cancer treated in our Center. Data were collected from patients medical records and analyzed using Epi Info software. 1277 patients were treated in our Center. 99.5% were females, mean age 50.20 ± 11.34 years. The most common histological type was invasive ductal carcinoma (80.7% of cases). It was diagnosed at an early stage (56,9%). The most common molecular phenotype was luminal A (41.4% of cases). Luminal B, HER2 and triple negatives occurred in 10.4%, 6.3%, 11.2% of cases respectively. The study of tumor phenotype in patients with breast cancer helps clinician make treatment choice and policy makers implement programs against this disease.

  5. Molecular profiling of ADAM12 gene in breast cancers.

    PubMed

    Nariţa, Diana; Anghel, A; Seclaman, E; Ilina, R; Cireap, Natalia; Ursoniu, S

    2010-01-01

    ADAMs (a disintegrin and metalloproteinase) family have been associated with the process of proteolytic "shedding" of membrane-associated proteins ectodomain and hence the rapid modulation of key cell signaling pathways in tissues microenvironment. A variety of cytokines, chemokines and growth factors which are initially produced as transmembrane proforms are activated by these sheddase activities. ADAM12 is highly expressed in rapidly growing tissues such as placenta and malignant tumors and it was found as one of the Candidate Cancer Genes in a comprehensive mutational analysis of human breast cancers. Our aim was to determine the gene expression profile of ADAM12 in breast cancers in comparison with normal breast and to correlate their level of expression with the clinical and pathological characteristics of breast cancers. Gene expression of ADAM12 spliced variants (12L and 12S) was evaluated using quantitative reverse-transcription PCR in samples obtained by laser capture microdissection from 38 patients with breast cancers and compared with adjacent healthy breast tissues. Both ADAM12L and 12S expression were significantly up-regulated in breast cancers, while in the normal breast, we found a very low expression. ADAM12L expression was significantly correlated with the histopathological types and, although not statistically significant, ADAM12 both variants were up-regulated in high-grade, highly-proliferative and HER2÷neu positive tumors. From these preliminary results, we found that ADAM12 could be an interesting marker and eventually a therapeutic target for breast cancer.

  6. Gene expression profiling of breast cancer in Lebanese women

    PubMed Central

    Makoukji, Joelle; Makhoul, Nadine J.; Khalil, Maya; El-Sitt, Sally; Aldin, Ehab Saad; Jabbour, Mark; Boulos, Fouad; Gadaleta, Emanuela; Sangaralingam, Ajanthah; Chelala, Claude; Boustany, Rose-Mary; Tfayli, Arafat

    2016-01-01

    Breast cancer is commonest cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. Molecular alterations in breast cancer are complex and involve cross-talk between multiple signaling pathways. The aim of this study is to extract a unique mRNA fingerprint of breast cancer in Lebanese women using microarray technologies. Gene-expression profiles of 94 fresh breast tissue samples (84 cancerous/10 non-tumor adjacent samples) were analyzed using GeneChip Human Genome U133 Plus 2.0 arrays. Quantitative real-time PCR was employed to validate candidate genes. Differentially expressed genes between breast cancer and non-tumor tissues were screened. Significant differences in gene expression were established for COL11A1/COL10A1/MMP1/COL6A6/DLK1/S100P/CXCL11/SOX11/LEP/ADIPOQ/OXTR/FOSL1/ACSBG1 and C21orf37. Pathways/diseases representing these genes were retrieved and linked using PANTHER®/Pathway Studio®. Many of the deregulated genes are associated with extracellular matrix, inflammation, angiogenesis, metastasis, differentiation, cell proliferation and tumorigenesis. Characteristics of breast cancers in Lebanese were compared to those of women from Western populations to explain why breast cancer is more aggressive and presents a decade earlier in Lebanese victims. Delineating molecular mechanisms of breast cancer in Lebanese women led to key genes which could serve as potential biomarkers and/or novel drug targets for breast cancer. PMID:27857161

  7. Gene expression profiling of breast cancer in Lebanese women.

    PubMed

    Makoukji, Joelle; Makhoul, Nadine J; Khalil, Maya; El-Sitt, Sally; Aldin, Ehab Saad; Jabbour, Mark; Boulos, Fouad; Gadaleta, Emanuela; Sangaralingam, Ajanthah; Chelala, Claude; Boustany, Rose-Mary; Tfayli, Arafat

    2016-11-18

    Breast cancer is commonest cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. Molecular alterations in breast cancer are complex and involve cross-talk between multiple signaling pathways. The aim of this study is to extract a unique mRNA fingerprint of breast cancer in Lebanese women using microarray technologies. Gene-expression profiles of 94 fresh breast tissue samples (84 cancerous/10 non-tumor adjacent samples) were analyzed using GeneChip Human Genome U133 Plus 2.0 arrays. Quantitative real-time PCR was employed to validate candidate genes. Differentially expressed genes between breast cancer and non-tumor tissues were screened. Significant differences in gene expression were established for COL11A1/COL10A1/MMP1/COL6A6/DLK1/S100P/CXCL11/SOX11/LEP/ADIPOQ/OXTR/FOSL1/ACSBG1 and C21orf37. Pathways/diseases representing these genes were retrieved and linked using PANTHER(®)/Pathway Studio(®). Many of the deregulated genes are associated with extracellular matrix, inflammation, angiogenesis, metastasis, differentiation, cell proliferation and tumorigenesis. Characteristics of breast cancers in Lebanese were compared to those of women from Western populations to explain why breast cancer is more aggressive and presents a decade earlier in Lebanese victims. Delineating molecular mechanisms of breast cancer in Lebanese women led to key genes which could serve as potential biomarkers and/or novel drug targets for breast cancer.

  8. [Prevalence and profile of the elderly home care valid suffering in a private residence falls].

    PubMed

    Pellicer García, Begoña; Juárez Vela, Raúl; Delgado Sevilla, David; Redondo Castan, Luis Carlos; Martínez Abadía, Blanca; Ramón Arbués, Enrique

    2013-12-01

    To estimate the prevalence of falls in people over 65 years old institutionalized and to know the elderly profile of those who suffered falls in the last 12 months. It was performed a transversal-descriptive study. The instruments used were the Mini-Mental State Examination (MMSE-35 Lobo, 1979) and the Questionnaire (1989) for the study of falls in the elderly. It was collected the following variables: age, sex, BMI, weight, height, assistive devices for ambulation, fear of falling, falling place, difficulty in actions, sort of footwear, fall time, lighting at the fall time, objects that could favour the fall, type of fall and contact with the health system. All of the participants in this study were 51 valid elderly and institutionalized. In the last 12 months, 21 individuals suffered a fall. This is equivalent to 41,17% in both sexes, being a 61,91% for women and 38,09% for men. The BMI average in all of the study participants amounts to 26,6 kg/m2. By the MCA, it was observed how the overweight variable is, without any doubt, linked with suffering a fall. In the Mantel-Haenszel test, it was obtained that women between 85-90 years old had a 42% more probability of falling. The places with the highest prevalence of falls were inside the nursing home with 71,4%. The women reported a fear sensation in order to suffer a second fall by 84,6% and the men by 75% over the total falls which were produced in both sexes. From the elderly who suffered falls, 52,38% used technical assistance to ambulate, compared to the 47,61% who didn't use. The footwear, which was used the most at the time of the fall, was slippers with 38,1%. Most falls took place in the morning with a percentage of 47,6% and the 90,5% of the falls occurred with an optimal lighting and in the 71,4% of the falls, there wasn't anything that favoured them. The 66,7% of the falls didn't need health care after them and the 52,4% of the falls had no physical consequences. The main difficulties that arise in our

  9. A Study on the Secure User Profiling Structure and Procedure for Home Healthcare Systems.

    PubMed

    Ko, Hoon; Song, MoonBae

    2016-01-01

    Despite of various benefits such as a convenience and efficiency, home healthcare systems have some inherent security risks that may cause a serious leak on personal health information. This work presents a Secure User Profiling Structure which has the patient information including their health information. A patient and a hospital keep it at that same time, they share the updated data. While they share the data and communicate, the data can be leaked. To solve the security problems, a secure communication channel with a hash function and an One-Time Password between a client and a hospital should be established and to generate an input value to an OTP, it uses a dual hash-function. This work presents a dual hash function-based approach to generate the One-Time Password ensuring a secure communication channel with the secured key. In result, attackers are unable to decrypt the leaked information because of the secured key; in addition, the proposed method outperforms the existing methods in terms of computation cost.

  10. Profiling early outcomes during the transition from hospital to home after brain injury.

    PubMed

    Turner, Benjamin; Fleming, Jennifer; Cornwell, Petrea; Haines, Terry; Ownsworth, Tamara

    2009-01-01

    To profile early outcomes during the transition from hospital to home for individuals with acquired brain injury (ABI) and their family caregivers. Prospective longitudinal study with data collected at three time points: pre-discharge and 1- and 3-months post-discharge. Participants included 26 individuals with ABI and 26 family caregivers, who were assessed on measures of global functioning, psychosocial reintegration, health-related quality-of-life and emotional well-being. Changes in outcomes over time and group comparisons were examined using repeated measures ANOVAs with relevant post-hoc analyses. Participants typically demonstrated improved global functioning and psychosocial reintegration during the transition period, with closer alignment of perspectives (i.e. comparisons between self-ratings of participants with ABI and ratings of family caregivers) at 3-months post-discharge on the occupational activities and living skills domains. Additionally, levels of depression and stress reported by participants with ABI were observed to increase over time. Collectively, the results highlight the critical nature of the transition phase for psychosocial reintegration and emotional adjustment and support the need for holistic approaches to transition-specific interventions.

  11. [The current status of home palliative care for patients with advanced cancer at the Jikei University School of Medicine].

    PubMed

    Nagasaki, Eijiro; Sakuyama, Toshikazu; Hayashi, Kazumi; Sakaji, Yukie; Aoki, Masako; Naito, Yasuko; Arakawa, Yasuhiro; Uwagawa, Tadashi; Kobayashi, Tadashi; Aiba, Keisuke

    2014-12-01

    Medical oncologists are involved in cancer chemotherapy as well as end-of-life care. Recently, an increased number of patients with advanced cancer have expressed their preference to receive palliative care at their home during the end-of-life period, and several home medical care providers have aimed to provide such a service. The number of cancer patients who wish to receive home palliative care has also increased at our institution. We reviewed the characteristics of advanced cancer patients who received chemotherapy and who eventually received homecare from 2012 to 2014. The total number of patients was 22. Of these, 9 had breast cancer(40.9%)and 8 had colorectal cancer(36.4%). The median age was 68(range 36-90) years. Half of these patients died at home. The median duration of homecare to death was 64.5(range 12-252)days. Approximately 70% of patients were able to remain at home for over a month, but 3 patients died within 2 weeks at home and 1 patient returned to the hospital after 10 days of homecare due to disease progression. While palliative care in the home setting is valued by many cancer patients in the end-of-life period, close monitoring is needed for patients with rapidly progressing disease.

  12. [Home care for cancer patients previously treated at other medical facilities].

    PubMed

    Okino, Takashi; Okino, Akie; Miyamoto, Hiroko; Yamawaki, Mitsuko; Yamamoto, Toshiyuki; Tanaka, Toshiki

    2013-12-01

    Nine cancer patients who were treated at other medical facilities were referred to the Kohka Public Hospital (KPH) to receive further cancer treatment or terminal care. Of these patients, 7 were men and 2 were women, and their mean age was 58.8 years. All the patients had unresectable cancer invasion or metastases. Their Eastern Cooperative Oncology Group performance status was either 3 or 4. Six of the 9 patients were first admitted to KPH and then discharged to home care. Two of these 6 patients died at home. The other 4 patients were ultimately re-admitted. The problem was that prognosis was not predicted accurately in some of these patients. Two of the 9 patients were managed by home care and died on days 8 and 13 after the initiation of home care. One patient returned to the previous hospital with the hope of receiving further treatment and palliative care. Patient information had to be available at presentation to all persons involved in the management of the patient and we had to prepare for patient care. Additionally, patients should be informed about serious conditions and poor prognosis without delay.

  13. Proteomic profiling of lymphocytes in autoimmunity, inflammation and cancer.

    PubMed

    Zhou, Jiebai; Zhu, Zhitu; Bai, Chunxue; Sun, Hongzhi; Wang, Xiangdong

    2014-01-07

    Lymphocytes play important roles in the balance between body defense and noxious agents involved in a number of diseases, e.g. autoimmune diseases, allergic inflammation and cancer. The proteomic analyses have been applied to identify and validate disease-associated and disease-specific biomarkers for therapeutic strategies of diseases. The proteomic profiles of lymphocytes may provide more information to understand their functions and roles in the development of diseases, although proteomic approaches in lymphocytes are still limited. The present review overviewed the proteomics-based studies on lymphocytes to headlight the proteomic profiles of lymphocytes in diseases, such as autoimmune diseases, allergic inflammation and cancer, with a special focus on lung diseases. We will explore the potential significance of diagnostic biomarkers and therapeutic targets from the current status in proteomic studies of lymphocytes and discuss the value of the currently available proteomic methodologies in the lymphocytes research.

  14. Proteomic profiling of lymphocytes in autoimmunity, inflammation and cancer

    PubMed Central

    2014-01-01

    Lymphocytes play important roles in the balance between body defense and noxious agents involved in a number of diseases, e.g. autoimmune diseases, allergic inflammation and cancer. The proteomic analyses have been applied to identify and validate disease-associated and disease-specific biomarkers for therapeutic strategies of diseases. The proteomic profiles of lymphocytes may provide more information to understand their functions and roles in the development of diseases, although proteomic approaches in lymphocytes are still limited. The present review overviewed the proteomics-based studies on lymphocytes to headlight the proteomic profiles of lymphocytes in diseases, such as autoimmune diseases, allergic inflammation and cancer, with a special focus on lung diseases. We will explore the potential significance of diagnostic biomarkers and therapeutic targets from the current status in proteomic studies of lymphocytes and discuss the value of the currently available proteomic methodologies in the lymphocytes research. PMID:24397796

  15. Unmet home healthcare needs and quality of life in cancer patients: a hospital-based Turkish sample.

    PubMed

    Ataman, Gülsen; Erbaydar, Tugrul

    2017-07-01

    Home healthcare services in Turkey are provided primarily to patients that are bedridden or seriously disabled. There are no such services integrated with hospital services that are specifically designed for cancer patients. The present study aimed to explore the home healthcare needs of cancer patients and their experiences related to unmet home healthcare needs. The study included 394 adult cancer patients who were followed up at the surgical oncology department of a university hospital. A 37-item, study-specific questionnaire and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for cancer patients (EORTC-QLQ-C30) were administered, and patient clinical records were evaluated. Home healthcare was provided primarily by the patients' immediate family members; the professional home healthcare usage rate was only 2.8%. Patient quality of life (QoL) was negatively affected by cancer, especially those with stage three and four disease. The frequency of the need for home healthcare services due to disease-related health problems during the 30 days prior to administration of the questionnaires was as follows: pain (62.9%), surgical wound care (44.9%), injection of therapeutics (52.3%), gastrointestinal complaints (51.8%), anxiety (87.1%), psychosocial assistance (77.2%) and information about cancer (94.4%). In the absence of home healthcare services, the patients primarily used institutional healthcare services to meet their needs; otherwise, their needs were not met. The physical and psychosocial problems that cancer patients experience could be solved in most cases by professional home healthcare services. Hospital-integrated home healthcare services might not only improve cancer patient QoL but might also increase the effectiveness of hospital-based healthcare services. © 2017 John Wiley & Sons Ltd.

  16. Early Lung Cancer Detection via Global Protein Modification Profiles

    DTIC Science & Technology

    2013-12-01

    remission at 3 years (low risk) following diagnosis (Figure 2). The top graph shows the mean difference in the observed expression of the first 100...in patients with remission at 3 years. These preliminary results suggest that the PTM profiles of Lung cancer tumors with poor prognosis may be...highly divergent from that of tumors from patients that were in remission at 3 years following diagnosis and these differences can be detected using

  17. Plasma extracellular RNA profiles in healthy and cancer patients

    PubMed Central

    Yuan, Tiezheng; Huang, Xiaoyi; Woodcock, Mark; Du, Meijun; Dittmar, Rachel; Wang, Yuan; Tsai, Susan; Kohli, Manish; Boardman, Lisa; Patel, Tushar; Wang, Liang

    2016-01-01

    Extracellular vesicles are selectively enriched in RNA that has potential as disease biomarkers. To systemically characterize circulating extracellular RNA (exRNA) profiles, we performed RNA sequencing analysis on plasma extracellular vesicles derived from 50 healthy individuals and 142 cancer patients. Of ~12.6 million raw reads for each individual, the number of mappable reads aligned to RNA references was ~5.4 million including miRNAs (~40.4%), piwiRNAs (~40.0%), pseudo-genes (~3.7%), lncRNAs (~2.4%), tRNAs (~2.1%), and mRNAs (~2.1%). By expression stability testing, we identified a set of miRNAs showing relatively consistent expression, which may serve as reference control for exRNA quantification. By performing multivariate analysis of covariance, we identified significant associations of these exRNAs with age, sex and different types of cancers. In particular, down-regulation of miR-125a-5p and miR-1343-3p showed an association with all cancer types tested (false discovery rate <0.05). We developed multivariate statistical models to predict cancer status with an area under the curve from 0.68 to 0.92 depending cancer type and staging. This is the largest RNA-seq study to date for profiling exRNA species, which has not only provided a baseline reference profile for circulating exRNA, but also revealed a set of RNA candidates for reference controls and disease biomarkers. PMID:26786760

  18. Random Subspace Aggregation for Cancer Prediction with Gene Expression Profiles

    PubMed Central

    Yuan, Xiguo; Zhang, Junying

    2016-01-01

    Background. Precisely predicting cancer is crucial for cancer treatment. Gene expression profiles make it possible to analyze patterns between genes and cancers on the genome-wide scale. Gene expression data analysis, however, is confronted with enormous challenges for its characteristics, such as high dimensionality, small sample size, and low Signal-to-Noise Ratio. Results. This paper proposes a method, termed RS_SVM, to predict gene expression profiles via aggregating SVM trained on random subspaces. After choosing gene features through statistical analysis, RS_SVM randomly selects feature subsets to yield random subspaces and training SVM classifiers accordingly and then aggregates SVM classifiers to capture the advantage of ensemble learning. Experiments on eight real gene expression datasets are performed to validate the RS_SVM method. Experimental results show that RS_SVM achieved better classification accuracy and generalization performance in contrast with single SVM, K-nearest neighbor, decision tree, Bagging, AdaBoost, and the state-of-the-art methods. Experiments also explored the effect of subspace size on prediction performance. Conclusions. The proposed RS_SVM method yielded superior performance in analyzing gene expression profiles, which demonstrates that RS_SVM provides a good channel for such biological data. PMID:27999797

  19. Going Home to Kansas | Center for Cancer Research

    Cancer.gov

    In June 2011, at the age of 34 and despite regular screenings, Aricca Wallace was diagnosed with stage 3 cervical cancer. Raising two small children with her husband, and otherwise healthy, she was ready to fight. “I was young and was able to handle the aggressive chemotherapy and radiation. I thought everything would be fine,” said Wallace.

  20. Bone metastasis from lung cancer identified by genetic profiling

    PubMed Central

    Liu, Zhu-Lin; Wang, Chun; Chen, Hui-Jiao; Li, Xue; Dai, Li-Jun; Ding, Zhen-Yu

    2017-01-01

    Cancer metastasis remains responsible for the vast majority of cases of cancer-related morbidity and mortality. Metastasis, by its definition, is the spread of cancer from the primary site to the distant tissues. Advancing the scientific and clinical understanding of cancer metastasis is a high priority. The prerequisite requirement for pathological consistency may be compromised during metastasis. The present study reports the case of a cancer patient with different pathological types. The patient presented with pain in the neck and right hip, as well as weight loss. He underwent whole-body positron emission tomography-computed tomography, which identified a mass in the lung and abnormal metabolism of the bone. Biopsies of the ilium and lung were performed and he was shown to have lung adenocarcinoma and bone squamous carcinoma. The morphology and immunohistochemical patterns were completely different, while each lesion harbored an identical genetic profile. The bone lesion was identified to be a metastasis from the lung cancer. The patient was prescribed an epithelial growth factor receptor inhibitor, which resulted in a partial response in the lung mass and alleviation of the patient's bone pain. Through this case study, we advocate the importance of using genetic testing in addition to pathological assessment. PMID:28356968

  1. Glycan profiling of endometrial cancers using lectin microarray.

    PubMed

    Nishijima, Yoshihiro; Toyoda, Masashi; Yamazaki-Inoue, Mayu; Sugiyama, Taro; Miyazawa, Masaki; Muramatsu, Toshinari; Nakamura, Kyoko; Narimatsu, Hisashi; Umezawa, Akihiro; Mikami, Mikio

    2012-10-01

    Cell surface glycans change during the process of malignant transformation. To characterize and distinguish endometrial cancer and endometrium, we performed glycan profiling using an emerging modern technology, lectin microarray analysis. The three cell lines, two from endometrial cancers [well-differentiated type (G1) and poorly differentiated type (G3)] and one from normal endometrium, were successfully categorized into three independent groups by 45 lectins. Furthermore, in cancer cells, a clear difference between G1 and G3 type was observed for the glycans recognized with six lectins, Ulex europaeus agglutinin I (UEA-I), Sambucus sieboldiana agglutinin (SSA), Sambucus nigra agglutinin (SNA), Trichosanthes japonica agglutinin I (TJA-I), Amaranthus caudatus agglutinin (ACA), and Bauhinia purpurea lectin (BPL). The lectin microarray analysis using G3 type tissues demonstrated that stage I and stage III or IV were distinguished depending on signal pattern of three lectins, Dolichos biflorus agglutinin (DBA), BPL, and ACA. In addition, the analysis of the glycans on the ovarian cancer cells showed that only anticancer drug-sensitive cell lines had almost no activities to specific three lectins. Glycan profiling by the lectin microarray may be used to assess the characteristics of tumors and potentially to predict the success of chemotherapy treatment.

  2. A sense of security for cancer patients at home: the role of community nurses.

    PubMed

    McKenzie, Heather; Boughton, Maureen; Hayes, Lillian; Forsyth, Sue; Davies, Michelle; Underwood, Emma; McVey, Peta

    2007-07-01

    The present paper reports on a qualitative research project designed to expose the presently unrecognised minutiae of community nurses' work with cancer patients at home, and to identify the ways in which these, combined to form comprehensive care episodes, contribute to physical and psychosocial well-being. The project was conducted in two locations in New South Wales, Australia, one metropolitan and one rural. The research model focused on particular nurse-patient encounters, and involved pre- and post-encounter interviews with nurses, post-encounter interviews with patients and carers, and observation of the encounters themselves. Participants included generalist community nurses, cancer patients being cared for at home, and their primary carers where appropriate. This research demonstrates that regular contact with generalist community nurses is associated with a strong sense of security about the immediate situation for home-based cancer patients and their primary carers. This sense of security is a significant component of patient and carer physical and psychosocial well-being, and may have implications for health services utilisation. In the present paper, the authors outline the factors underpinning this sense of security, and argue that these findings contribute important new knowledge that is vital for contemporary debates about role responsibilities and continuity of care for cancer patients.

  3. Home energy efficiency and radon related risk of lung cancer: modelling study

    PubMed Central

    Milner, James; Shrubsole, Clive; Das, Payel; Jones, Benjamin; Ridley, Ian; Chalabi, Zaid; Hamilton, Ian; Armstrong, Ben; Davies, Michael

    2014-01-01

    Objective To investigate the effect of reducing home ventilation as part of household energy efficiency measures on deaths from radon related lung cancer. Design Modelling study. Setting England. Intervention Home energy efficiency interventions, motivated in part by targets for reducing greenhouse gases, which entail reduction in uncontrolled ventilation in keeping with good practice guidance. Main outcome measures Modelled current and future distributions of indoor radon levels for the English housing stock and associated changes in life years due to lung cancer mortality, estimated using life tables. Results Increasing the air tightness of dwellings (without compensatory purpose-provided ventilation) increased mean indoor radon concentrations by an estimated 56.6%, from 21.2 becquerels per cubic metre (Bq/m3) to 33.2 Bq/m3. After the lag in lung cancer onset, this would result in an additional annual burden of 4700 life years lost and (at peak) 278 deaths. The increases in radon levels for the millions of homes that would contribute most of the additional burden are below the threshold at which radon remediation measures are cost effective. Fitting extraction fans and trickle ventilators to restore ventilation will help offset the additional burden but only if the ventilation related energy efficiency gains are lost. Mechanical ventilation systems with heat recovery may lower radon levels and the risk of cancer while maintaining the advantage of energy efficiency for the most airtight dwellings but there is potential for a major adverse impact on health if such systems fail. Conclusion Unless specific remediation is used, reducing the ventilation of dwellings will improve energy efficiency only at the expense of population wide adverse impact on indoor exposure to radon and risk of lung cancer. The implications of this and other consequences of changes to ventilation need to be carefully evaluated to ensure that the desirable health and environmental benefits of

  4. Home energy efficiency and radon related risk of lung cancer: modelling study.

    PubMed

    Milner, James; Shrubsole, Clive; Das, Payel; Jones, Benjamin; Ridley, Ian; Chalabi, Zaid; Hamilton, Ian; Armstrong, Ben; Davies, Michael; Wilkinson, Paul

    2014-01-10

    To investigate the effect of reducing home ventilation as part of household energy efficiency measures on deaths from radon related lung cancer. Modelling study. England. Home energy efficiency interventions, motivated in part by targets for reducing greenhouse gases, which entail reduction in uncontrolled ventilation in keeping with good practice guidance. Modelled current and future distributions of indoor radon levels for the English housing stock and associated changes in life years due to lung cancer mortality, estimated using life tables. Increasing the air tightness of dwellings (without compensatory purpose-provided ventilation) increased mean indoor radon concentrations by an estimated 56.6%, from 21.2 becquerels per cubic metre (Bq/m(3)) to 33.2 Bq/m(3). After the lag in lung cancer onset, this would result in an additional annual burden of 4700 life years lost and (at peak) 278 deaths. The increases in radon levels for the millions of homes that would contribute most of the additional burden are below the threshold at which radon remediation measures are cost effective. Fitting extraction fans and trickle ventilators to restore ventilation will help offset the additional burden but only if the ventilation related energy efficiency gains are lost. Mechanical ventilation systems with heat recovery may lower radon levels and the risk of cancer while maintaining the advantage of energy efficiency for the most airtight dwellings but there is potential for a major adverse impact on health if such systems fail. Unless specific remediation is used, reducing the ventilation of dwellings will improve energy efficiency only at the expense of population wide adverse impact on indoor exposure to radon and risk of lung cancer. The implications of this and other consequences of changes to ventilation need to be carefully evaluated to ensure that the desirable health and environmental benefits of home energy efficiency are not compromised by avoidable negative impacts

  5. Building America Top Innovations 2014 Profile: Cost-Optimized Attic Insulation Solution for Factory-Built Homes

    SciTech Connect

    none,

    2014-11-01

    This 2014 Top Innovation profile describes a low-cost, low-tech attic insulation technique developed by the ARIES Building America team with help from Southern Energy Homes and Johns Manville. Increasing attic insulation in manufactured housing has been a significant challenge due to cost, production and transportation constraints. The simplicity of this dense-pack solution to increasing attic insulation R-value promises real hope for widespread industry adoption.

  6. Mutational Profile of Metastatic Breast Cancers: A Retrospective Analysis.

    PubMed

    Lefebvre, Celine; Bachelot, Thomas; Filleron, Thomas; Pedrero, Marion; Campone, Mario; Soria, Jean-Charles; Massard, Christophe; Lévy, Christelle; Arnedos, Monica; Lacroix-Triki, Magali; Garrabey, Julie; Boursin, Yannick; Deloger, Marc; Fu, Yu; Commo, Frédéric; Scott, Véronique; Lacroix, Ludovic; Dieci, Maria Vittoria; Kamal, Maud; Diéras, Véronique; Gonçalves, Anthony; Ferrerro, Jean-Marc; Romieu, Gilles; Vanlemmens, Laurence; Mouret Reynier, Marie-Ange; Théry, Jean-Christophe; Le Du, Fanny; Guiu, Séverine; Dalenc, Florence; Clapisson, Gilles; Bonnefoi, Hervé; Jimenez, Marta; Le Tourneau, Christophe; André, Fabrice

    2016-12-01

    Major advances have been achieved in the characterization of early breast cancer (eBC) genomic profiles. Metastatic breast cancer (mBC) is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing. Whole-exome sequencing was performed on 216 tumor-blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO) prospective trials. Mutational profiles from 772 primary breast tumors from The Cancer Genome Atlas (TCGA) were used as a reference for comparing primary and mBC mutational profiles. Twelve genes (TP53, PIK3CA, GATA3, ESR1, MAP3K1, CDH1, AKT1, MAP2K4, RB1, PTEN, CBFB, and CDKN2A) were identified as significantly mutated in mBC (false discovery rate [FDR] < 0.1). Eight genes (ESR1, FSIP2, FRAS1, OSBPL3, EDC4, PALB2, IGFN1, and AGRN) were more frequently mutated in mBC as compared to eBC (FDR < 0.01). ESR1 was identified both as a driver and as a metastatic gene (n = 22, odds ratio = 29, 95% CI [9-155], p = 1.2e-12) and also presented with focal amplification (n = 9) for a total of 31 mBCs with either ESR1 mutation or amplification, including 27 hormone receptor positive (HR+) and HER2 negative (HER2-) mBCs (19%). HR+/HER2- mBC presented a high prevalence of mutations on genes located on the mechanistic target of rapamycin (mTOR) pathway (TSC1 and TSC2) as compared to HR+/HER2- eBC (respectively 6% and 0.7%, p = 0.0004). Other actionable genes were more frequently mutated in HR+ mBC, including ERBB4 (n = 8), NOTCH3 (n = 7), and ALK (n = 7). Analysis of mutational signatures revealed a significant increase in APOBEC-mediated mutagenesis in HR+/HER2- metastatic tumors as compared to primary TCGA samples (p < 2e-16). The main limitations of this study include the absence of bone metastases and the size of the cohort, which

  7. Profile of morbidity among elderly at home health care service in Southern Saudi Arabia

    PubMed Central

    Al-Modeer, Mohamed A.; Hassanien, Noha S.; Jabloun, Chauky M.

    2013-01-01

    Background: This study aimed to determine the profile of morbidity among elderly registered at home health care service in the Armed Forces Hospital of Southern Region, Kingdom of Saudi Arabia. Materials and Methods: A retrospective study was conducted (over a period of 6 months during year 2011) and data was collected by reviewing of medical records of all elderly patients of elderly. Results: The total number of elderly ≥ 60 years were 880. The most prevalent morbidity is hypertension (59.1%) followed by diabetes mellitus (57.3%), stroke (34.9%), dementia (28.5%), osteoarthritis (24.2%) and Alzheimer (21.4%). Females are at higher risks of having many types elderly diseases compared to males. The highest risk was for obesity (OR = 9.1; 95% CI = 3.51- 12.8), followed by osteoporosis (OR = 8.7; 95% CI = 15.10 – 9.13) and fracture neck femur (OR = 3.9; 95 CI = 2.11 – 6.91). In addition, females were also at higher risks of having Osteoarthritis and thyroid disorder. On the other hand, males are more susceptible to hypertension (OR = 1.4; 95 % CI = 1.07 – 1.85), stroke (OR = 1.3; 95 % CI = 1.08 – 1.89) and renal diseases (OR = 2.4; 95% CI = 1.25 – 4.54). Conclusion: It is concluded that there is a great need for preventive, curative and rehabilitative program in order to introduce high quality of health care services to elderly. PMID:23723732

  8. Patient Navigators: Agents of Creating Community-Nested Patient-Centered Medical Homes for Cancer Care

    PubMed Central

    Simon, Melissa A.; Samaras, Athena T.; Nonzee, Narissa J.; Hajjar, Nadia; Frankovich, Carmi; Bularzik, Charito; Murphy, Kara; Endress, Richard; Tom, Laura S.; Dong, XinQi

    2016-01-01

    Patient navigation is an internationally utilized, culturally grounded, and multifaceted strategy to optimize patients’ interface with the health-care team and system. The DuPage County Patient Navigation Collaborative (DPNC) is a campus–community partnership designed to improve access to care among uninsured breast and cervical cancer patients in DuPage County, IL. Importantly, the DPNC connects community-based social service delivery with the patient-centered medical home to achieve a community-nested patient-centered medical home model for cancer care. While the patient navigator experience has been qualitatively documented, the literature pertaining to patient navigation has largely focused on efficacy outcomes and program cost effectiveness. Here, we uniquely highlight stories of women enrolled in the DPNC, told from the perspective of patient navigators, to shed light on the myriad barriers that DPNC patients faced and document the strategies DPNC patient navigators implemented. PMID:27594792

  9. Opportunities-to-Learn at Home: Profiles of Students with and without Reaching Science Proficiency

    ERIC Educational Resources Information Center

    Liu, Xiufeng; Whitford, Melinda

    2011-01-01

    This study examines the relationship between opportunity-to-learn (OTL) at home and students' attainment of science proficiency. The data set used was the 2006 PISA science US national sample. Data mining was used to create patterns of association between home OTL variables and student attainment of science proficiency. It was found that students…

  10. Detection of Bladder Cancer Using Proteomic Profiling of Urine Sediments

    PubMed Central

    Majewski, Tadeusz; Spiess, Philippe E.; Bondaruk, Jolanta; Black, Peter; Clarke, Charlotte; Benedict, William; Dinney, Colin P.; Grossman, Herbert Barton; Tang, Kuang S.; Czerniak, Bogdan

    2012-01-01

    We used protein expression profiles to develop a classification rule for the detection and prognostic assessment of bladder cancer in voided urine samples. Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a training set of 85 voided urine samples (32 controls and 53 bladder cancer), and a blinded testing set of 68 voided urine samples (33 controls and 35 bladder cancer). Using t-tests, we identified 473 peaks showing significant differential expression across different categories of paired bladder tumor and adjacent urothelial samples compared to normal urothelium. Then the intensities of those 473 peaks were examined in a training set of voided urine samples. Using this approach, we identified 41 protein peaks that were differentially expressed in both sets of samples. The expression pattern of the 41 protein peaks was used to classify the voided urine samples as malignant or benign. This approach yielded a sensitivity and specificity of 59% and 90%, respectively, on the training set and 80% and 100%, respectively, on the testing set. The proteomic classification rule performed with similar accuracy in low- and high-grade bladder carcinomas. In addition, we used hierarchical clustering with all 473 protein peaks on 65 benign voided urine samples, 88 samples from patients with clinically evident bladder cancer, and 127 samples from patients with a history of bladder cancer to classify the samples into Cluster A or B. The tumors in Cluster B were characterized by clinically aggressive behavior with significantly shorter metastasis-free and disease-specific survival. PMID:22879988

  11. Detection of bladder cancer using proteomic profiling of urine sediments.

    PubMed

    Majewski, Tadeusz; Spiess, Philippe E; Bondaruk, Jolanta; Black, Peter; Clarke, Charlotte; Benedict, William; Dinney, Colin P; Grossman, Herbert Barton; Tang, Kuang S; Czerniak, Bogdan

    2012-01-01

    We used protein expression profiles to develop a classification rule for the detection and prognostic assessment of bladder cancer in voided urine samples. Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a training set of 85 voided urine samples (32 controls and 53 bladder cancer), and a blinded testing set of 68 voided urine samples (33 controls and 35 bladder cancer). Using t-tests, we identified 473 peaks showing significant differential expression across different categories of paired bladder tumor and adjacent urothelial samples compared to normal urothelium. Then the intensities of those 473 peaks were examined in a training set of voided urine samples. Using this approach, we identified 41 protein peaks that were differentially expressed in both sets of samples. The expression pattern of the 41 protein peaks was used to classify the voided urine samples as malignant or benign. This approach yielded a sensitivity and specificity of 59% and 90%, respectively, on the training set and 80% and 100%, respectively, on the testing set. The proteomic classification rule performed with similar accuracy in low- and high-grade bladder carcinomas. In addition, we used hierarchical clustering with all 473 protein peaks on 65 benign voided urine samples, 88 samples from patients with clinically evident bladder cancer, and 127 samples from patients with a history of bladder cancer to classify the samples into Cluster A or B. The tumors in Cluster B were characterized by clinically aggressive behavior with significantly shorter metastasis-free and disease-specific survival.

  12. A profile of skin cancer prevention media coverage in 2009.

    PubMed

    Cokkinides, Vilma; Kirkland, Deborah; Andrews, Kimberly; Sullivan, Kristen; Lichtenfeld, J Leonard

    2012-10-01

    Little is known about the coverage of skin cancer prevention messages in news print media. To perform a content analysis of mass-media articles from newspaper and magazines pertaining to skin cancer prevention in 4 specific months (January, May, July, and October) in 2009 and assess the extent of coverage of skin cancer prevention messages. We conducted a content analysis of 144 articles related to skin cancer prevention extracted from strategic media scans of selected months in 2009. We sought to provide the frequency of mass-media content categorized by theme and focus related to ultraviolet radiation (UVR) protection and risk-reducing behaviors. The audience for the vast majority (78%) of the articles was the general public. Among the assessed articles, more were published in May (49%) and July (35%) than in the remaining other months. The two most frequent themes focused on 'protection of the skin' (32%) and on 'skin cancer prevention' (23%) via risk reduction behavioral practices. Analysis of message content regarding UVR reduction practices showed that many mentioned 'use of sunscreen' (65% of messages) with the least-often mentioned behaviors being 'seek shade' (6.3%) and 'do not burn' (1.4%). In addition, a quarter of the articles lacked any content mentioning recommended UVR reduction behaviors. This study was limited to the narrow scope of articles published in 2009 and for selected months. This profile of mass-media content regarding skin cancer prevention revealed gaps in coverage of UVR reduction behaviors with possible room for improvement. Strategies for improving and comprehensiveness of coverage of recommended skin cancer prevention behaviors in the media are discussed. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  13. Pediatric Cancer CareLink--supporting home management of childhood leukemia.

    PubMed

    Goldsmith, D M; Silverman, L B; Safran, C

    2002-01-01

    We conducted a descriptive evaluation of an Internet-based system designed to support home management of childhood leukemia (Pediatric Cancer CareLink). Twenty-five parents of children with ALL and thirty-four clinicians were interviewed to identify functional requirements and to demonstrate the system's potential to improve the experience and outcomes of children with acute lymphoblastic leukemia (ALL). Parental interviews focused on: medication and side effect management in the home; communication with the health care team; and the use of a computer for ALL home management. Results from these interviews provide strong evidence that parents of children with ALL are struggling to manage the complexity of their children's care in the home. Parents revealed an urgent need for tools that would help them to safely organize the medicines that their children receive while on ALL protocols. Forty percent of parents needed to know more about what to expect during their child's therapy and how to be prepared for it. Clinician interviews focused on the clinical impact and workflow issues associated with such a system. Decision support, prescription refill management, and educational and emotional support functions were considered key components. Clinicians were concerned that such a system would increase their already overburdened workload. Conversely, parents believed that access to such a system would eliminate unnecessary phone calls to the care team. Our findings show that parents would embrace collaborative Internet-based tools that would help with the home management of their child's leukemia.

  14. Pediatric Cancer CareLink--supporting home management of childhood leukemia.

    PubMed Central

    Goldsmith, D. M.; Silverman, L. B.; Safran, C.

    2002-01-01

    We conducted a descriptive evaluation of an Internet-based system designed to support home management of childhood leukemia (Pediatric Cancer CareLink). Twenty-five parents of children with ALL and thirty-four clinicians were interviewed to identify functional requirements and to demonstrate the system's potential to improve the experience and outcomes of children with acute lymphoblastic leukemia (ALL). Parental interviews focused on: medication and side effect management in the home; communication with the health care team; and the use of a computer for ALL home management. Results from these interviews provide strong evidence that parents of children with ALL are struggling to manage the complexity of their children's care in the home. Parents revealed an urgent need for tools that would help them to safely organize the medicines that their children receive while on ALL protocols. Forty percent of parents needed to know more about what to expect during their child's therapy and how to be prepared for it. Clinician interviews focused on the clinical impact and workflow issues associated with such a system. Decision support, prescription refill management, and educational and emotional support functions were considered key components. Clinicians were concerned that such a system would increase their already overburdened workload. Conversely, parents believed that access to such a system would eliminate unnecessary phone calls to the care team. Our findings show that parents would embrace collaborative Internet-based tools that would help with the home management of their child's leukemia. PMID:12463833

  15. Managing occupations in everyday life for people with advanced cancer living at home.

    PubMed

    Peoples, Hanne; Brandt, Åse; Wæhrens, Eva E; la Cour, Karen

    2017-01-01

    People with advanced cancer are able to live for extended periods of time. Advanced cancer can cause functional limitations influencing the ability to manage occupations. Although studies have shown that people with advanced cancer experience occupational difficulties, there is only limited research that specifically explores how these occupational difficulties are managed. To describe and explore how people with advanced cancer manage occupations when living at home. A sub-sample of 73 participants from a larger occupational therapy project took part in the study. The participants were consecutively recruited from a Danish university hospital. Qualitative interviews were performed at the homes of the participants. Content analysis was applied to the data. Managing occupations were manifested in two main categories; (1) Conditions influencing occupations in everyday life and (2) Self-developed strategies to manage occupations. The findings suggest that people with advanced cancer should be supported to a greater extent in finding ways to manage familiar as well as new and more personally meaningful occupations to enhance quality of life.

  16. [Home parenteral nutrition in elderly patients with cancer: an observational prospective study].

    PubMed

    Seys, Patrick; Tadmouri, Abir; Senesse, Pierre; Radji, Abderraouf; Rotarski, Maciej; Balian, Axel; Culine, Stéphane; Dufour, Patrick; Chambrier, Cécile

    2014-03-01

    Malnutrition is a bad prognostic factor that reduces the quality of life (QoL) in patients with cancer. The objective was to assess the impact of home parenteral nutrition (HPN) on the QoL of elderly malnourished patients with cancer. This French prospective observational study included patients, aged 70 years or older, with cancer, for whom HPN was prescribed for at least 14 days. The patient, the physician and a family member or home caregiver had to fill in a questionnaire at inclusion and 28 days later. Included patients (n = 221) were mainly suffering from a digestive cancer. After HPN intake, improved weight was noticed in 68% and 14% of patients had reached the target weight. Improved global QoL was reported in 59% of patients. Physicians noticed a significant improvement for the same compounds. These results suggest a benefit of the HPN on the nutritional status and QoL in elderly patients with cancer. Further controlled randomised trials are needed to prove the benefit of HPN in the routine management of these patients.

  17. Home bowel cancer tests and informed choice--is current information sufficient?

    PubMed

    Howard, K; Salkeld, G

    2003-10-01

    To evaluate the type of information that is available to purchasers of home-based bowel cancer test kits. Manufacturers, pharmacies and independent testing programs were contacted to obtain faecal occult blood test (FOBT) kits. State cancer organisations were contacted for information on bowel cancer screening. Information on bowel cancer, the FOBT kit, the testing process and potential benefits and harms of the screening process were assessed using guidelines provided by the UK General Medical Council (GMC). FOBT kits and cancer organisation information provided adequate information on the purpose of screening, the screening process itself and potential benefits, but provided no information concerning uncertainties of screening or potential harms. On the basis of both the UK GMC criteria and patient desires for information, the information available at present falls short of being considered adequate for an informed decision to purchase a home-based FOBT. We must ensure adequate and balanced information is available to redress the present information asymmetry to facilitate informed participation in a potentially valuable public health initiative.

  18. Diagnosis of pancreatic cancer using serum proteomic profiling.

    PubMed

    Bhattacharyya, Sudeepa; Siegel, Eric R; Petersen, Gloria M; Chari, Suresh T; Suva, Larry J; Haun, Randy S

    2004-01-01

    In the United States, mortality rates from pancreatic cancer (PCa) have not changed significantly over the past 50 years. This is due, in part, to the lack of early detection methods for this particularly aggressive form of cancer. The objective of this study was to use high-throughput protein profiling technology to identify biomarkers in the serum proteome for the early detection of resectable PCa. Using surface-enhanced laser desorption/ionization mass spectrometry, protein profiles were generated from sera of 49 PCa patients and 54 unaffected individuals after fractionation on an anion exchange resin. The samples were randomly divided into a training set (69 samples) and test set (34 samples), and two multivariate analysis procedures, classification and regression tree and logistic regression, were used to develop classification models from these spectral data that could distinguish PCa from control serum samples. In the test set, both models correctly classified all of the PCa patient serum samples (100% sensitivity). Using the decision tree algorithm, a specificity of 93.5% was obtained, whereas the logistic regression model produced a specificity of 100%. These results suggest that high-throughput proteomics profiling has the capacity to provide new biomarkers for the early detection and diagnosis of PCa.

  19. Profile of black woman in Senegal with breast cancer.

    PubMed

    Gueye, M; Kane Gueye, S M; Ndiaye Gueye, M D; Gueye, L; Moreau, J-C

    2016-05-01

    To describe the profile of Senegalese black women with breast cancer. This is a retrospective and prospective study of patients receiving care for breast cancer in the breast diseases department of the Aristide Le Dantec Teaching Hospital in Dakar from 2010 through June 2014. 188 women patients met the inclusion criteria. Their mean age at diagnosis was 43.3 years. The age of onset of the first menses was early (<12 years) in 7 patients (4.9%). More than two thirds of the women (71.6%) were premenopausal at diagnosis. At least one pregnancy was reported by 161 women (86.1%) and 96.3 had given birth. Mean age at first pregnancy was 19.47 years, and 85.9% had had their first pregnancy before the age of 30. Similarly, 133 (87.3%) had breastfed, for a mean duration of 18.36 months. In our country, breast cancer occurs in young women, who had their first menses after 12 years, are premenopausal, had their first pregnancy before the age of 30, and breastfed for several months. These data suggest that further study of this profile is needed but that the testing policy must change drastically, to start much earlier than 50 years.

  20. Test Your Home for Radon, You May Prevent Lung Cancer Radon kills 21,000 Americans each year, readily available tests can warn of high levels in homes

    EPA Pesticide Factsheets

    (01/15/16 -Atlanta) - January is National Radon Action Month and the U.S. Environmental Protection Agency (EPA) encourages Americans around the country to test their homes for radon, the second leading cause of lung cancer. Make 2016 a healthier, safer new

  1. Cancer in nursing homes: characteristics and health-related quality of life among cognitively intact residents with and without cancer.

    PubMed

    Drageset, Jorunn; Eide, Geir Egil; Ranhoff, Anette Hylen

    2012-01-01

    Studies are lacking on how cancer influences physical, mental, and social functioning beyond comorbidity among older people without cognitive impairment in nursing homes (NHs). The objective was to study the sociodemographic characteristics and health-related quality of life (HRQOL) among NH residents with and without a cancer diagnosis, adjusting for comorbidity. This was a cross-sectional observation study: 30 NHs; 227 residents 65 to 102 years old: 60 with cancer and 167 without, at least 6 months' residence. All had Clinical Dementia Rating of 0.5 or less and could converse. Health-related quality of life was measured using the 36-item Short-Form Health Survey in face-to-face interviews. Sociodemographic variables and medical diagnoses were obtained from records. Possible differences in HRQOL, controlled for age, gender, marital status, education, length of stay, and comorbidity, were examined by multiple linear regression analyses. The most common cancer diagnoses were breast cancer among women (20%) and prostate cancer among men (12%). More residents with cancer were married (P = .007), reported more bodily pain (P = .17) and scored lower on all other HRQOL subscales, except for role-emotional. General health was worse than that of the residents without cancer (P = .04) after adjusting for sociodemographic variables but not for comorbidity (P = .06). Cognitively intact NH residents with cancer reported more pain and worse general health but better role limitation related to emotional problems compared with residents without cancer. The difference in general health was partly due to comorbidity. Nurses should pay attention to HRQOL among NH residents with cancer and especially observe and ensure pain treatment.

  2. Impact of Home Hospice Care on Patients with Advanced Lung Cancer: A Longitudinal Population-Based Study in Taiwan.

    PubMed

    Chiang, Jui-Kun; Kao, Yee-Hsin

    2016-04-01

    The effectiveness of home hospice care was helping patients to die at home, and reducing symptom burden. The study objective was to explore the impact of home hospice care on death at home, end-of-life (EOL) care, and health care costs among patients with advanced lung cancer in their last month of life. Using Taiwan's National Health Insurance Claims Database, we analyzed factors associated with home hospice care using logistic regression analysis. We enrolled 568 patients with advanced lung cancer under hospice care who died during 1997-2011, of which 238 (41.9%) received home hospice care. Compared with the inpatient hospice (IH) group, the home hospice (HH) group had a larger portion die at home (55.5% versus 22.1%, p < 0.001), but a smaller portion stayed in hospital more than 14 days in their last month of life (67.3% versus 40.8%, p < 0.001). The mean health care cost was less in the HH group than in the IH group (US $1,385.00 ± $1,370.00 and US $2,155.00 ± $1,739.00 [p < 0.001], respectively). Female patients' (p = 0.001) decreased hospital stay in the last month of life (p < 0.001) and longer hospice care duration (p = 0.003) were predictors of receiving home hospice care in advanced lung patients. Home hospice care enables patients with advanced lung cancer to increase the 33.4% chance of dying at home, to spend an average of eight-days less in hospital stay, and to save 35.7% health care costs in the last month of life, compared with their counterparts with only inpatient hospice care. Female patients' decreased hospital stay and longer hospice care duration were the predictors of receiving home hospice care.

  3. Effectiveness of the "Cancer Home-Life Intervention" on everyday activities and quality of life in people with advanced cancer living at home: a randomised controlled trial and an economic evaluation.

    PubMed

    Brandt, Å; Pilegaard, M S; Oestergaard, L G; Lindahl-Jacobsen, L; Sørensen, J; Johnsen, A T; la Cour, K

    2016-01-22

    During the past decade an increasing number of people live with advanced cancer mainly due to improved medical treatment. Research has shown that many people with advanced cancer have problems with everyday activities, which have negative impact on their quality of life, and that they spend a considerable part of their time at home. Still, research on interventions to support the performance of and participation in everyday activities is only scarcely available. Therefore, the occupational therapy-based "Cancer Home-Life Intervention" consisting of tailored adaptive interventions applied in the participant's home environment was developed. The objective of this study is to examine the effectiveness and cost-effectiveness of the Cancer Home-Life Intervention compared to usual care on the performance of and participation in everyday activities and quality of life in people with advanced cancer living at home. The study is a randomised, controlled trial (RCT) including an economic evaluation. The required sample size of 272 adults living at home will be recruited from outpatient clinics at two Danish hospitals. They should be diagnosed with cancer; evaluated incurable by the responsible oncologist; and with a functional level 1-2 on the WHO performance scale. The primary outcome is the quality of performance of activities of daily living. Secondary outcomes are problems with prioritised everyday activities; autonomy and participation; and health-related quality of life. Participants are randomly assigned to: a) The Cancer Home-Life Intervention in addition to usual care, and b) Usual care alone. The trial will show whether the Cancer Home-Life Intervention provides better support for people with advanced cancer living at home in performing and participating in everyday activities, and whether it contributes to their health-related quality of life. The economic evaluation alongside the RCT will show if the Cancer Home-Life Intervention is cost-effective. The trial will

  4. Home-based functional walking program for advanced cancer patients receiving palliative care: a case series

    PubMed Central

    2013-01-01

    Background Although meta-analyses have demonstrated that physical activity can positively impact quality of life outcomes in early stage cancer patients, it is not yet known whether these benefits can be extended to patients with advanced cancer. In a previous pilot survey of patients with advanced cancer with a median survival of 104 days, participants felt willing and able to participate in a physical activity intervention, and reported a strong preference for walking and home-based programming. Here, we report on the initial development and feasibility of a home-based functional walking program in patients with advanced cancer receiving palliative care. Methods Nine adult patients were recruited from outpatient palliative care clinics and palliative home care. A pilot intervention trial was conducted over a 6-week period. The McGill Quality of Life Questionnaire (MQOL), Late Life Function and Disability Instrument (LLFDI), Edmonton Symptom Assessment System (ESAS), Seniors Fitness Test, four-test balance scale, and grip strength, were performed pre- and post-intervention. Participants wore activPAL™ accelerometers to monitor ambulatory activity levels. Results Of the nine recruited participants, three participants dropped out prior to baseline testing due to hospital admission and feeling overwhelmed, and three participants dropped out during the intervention due to severe symptoms. Only three participants completed the intervention program, pre- and post-intervention assessments: two reported improvements in total MQOL scores, yet all three shared an overall trend towards worsening symptom and total fatigue scores post-intervention. Two participants passed away within 90 days of completing the intervention. Conclusions This case series demonstrates the challenges of a physical activity intervention in patients with advanced cancer receiving palliative care. Further feasibility research is required in this patient population. Trial registration This study is

  5. Implications of micro-RNA profiling for cancer diagnosis.

    PubMed

    Cummins, J M; Velculescu, V E

    2006-10-09

    Micro-RNAs (miRNAs) are a large class of small non-coding RNAs that regulate protein expression in eucaryotic cells. Initially believed to be unique to the nematode Caenorhabditis elegans, miRNAs are now recognized to be important gene regulatory elements in multicellular organisms and have been implicated in a variety of disease processes, including cancer. Advances in expression technologies have facilitated the high-throughput analysis of small RNAs, identifying novel miRNAs and showing that these genes may be aberrantly expressed in various human tumors. These studies suggest that miRNA expression profiling can be correlated with disease pathogenesis and prognosis, and may ultimately be useful in the management of human cancer.

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

    PubMed

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

    2014-08-01

    Breast cancer during pregnancy is rare and is associated with relatively poor prognosis. No information is available on its biological features at the genomic level. Using a dataset of 54 pregnant and 113 non-pregnant breast cancer patients, we evaluated the pattern of hot spot somatic mutations and did transcriptomic profiling using Sequenom and Affymetrix respectively. We performed gene set enrichment analysis to evaluate the pathways associated with diagnosis during pregnancy. We also evaluated the expression of selected cancer-related genes in pregnant and non-pregnant patients and correlated the results with changes occurring in the normal breast using a pregnant murine model. We finally investigated aberrations associated with disease-free survival (DFS). No significant differences in mutations were observed. Of the total number of patients, 18.6% of pregnant and 23% of non-pregnant patients had a PIK3CA mutation. Around 30% of tumors were basal, with no differences in the distribution of breast cancer molecular subtypes between pregnant and non-pregnant patients. Two pathways were enriched in tumors diagnosed during pregnancy: the G protein-coupled receptor pathway and the serotonin receptor pathway (FDR <0.0001). Tumors diagnosed during pregnancy had higher expression of PD1 (PDCD1; P=0.015), PDL1 (CD274; P=0.014), and gene sets related to SRC (P=0.004), IGF1 (P=0.032), and β-catenin (P=0.019). Their expression increased almost linearly throughout gestation when evaluated on the normal breast using a pregnant mouse model underscoring the potential effect of the breast microenvironment on tumor phenotype. No genes were associated with DFS in a multivariate model, which could be due to low statistical power. Diagnosis during pregnancy impacts the breast cancer transcriptome including potential cancer targets.

  7. Multiplexed Methylation Profiles of Tumor Suppressor Genes in Bladder Cancer

    PubMed Central

    Cabello, Maria José; Grau, Laura; Franco, Noreli; Orenes, Esteban; Alvarez, Miguel; Blanca, Ana; Heredero, Oscar; Palacios, Alberto; Urrutia, Manuel; Fernández, Jesus María; López-Beltrán, Antonio; Sánchez-Carbayo, Marta

    2011-01-01

    Changes in DNA methylation of tumor suppressors can occur early in carcinogenesis and are potentially important early indicators of cancer. The objective of this study was to assess the methylation of 25 tumor suppressor genes in bladder cancer using a methylation-specific (MS) multiplex ligation-dependent probe amplification assay (MLPA). Initial analyses in bladder cancer cell lines (n = 14) and fresh-frozen primary bladder tumor specimens (n = 31) supported the panel of genes selected being altered in bladder cancer. The process of MS-MLPA was optimized for its application in body fluids using two independent training and validation sets of urinary specimens (n = 146), including patients with bladder cancer (n = 96) and controls (n = 50). BRCA1 (71.0%), WT1 (38.7%), and RARB (38.7%) were the most frequently methylated genes in bladder tumors, with WT1 methylation being significantly associated with tumor stage (P = 0.011). WT1 and PAX5A were identified as methylated tumor suppressors. In addition, BRCA1, WT1, and RARB were the most frequently methylated genes in urinary specimens. Receiver operating characteristic curve analyses revealed significant diagnostic accuracies in both urinary sets for BRCA1, RARB, and WT1. The novelty of this report relates to applying MS-MLPA, a multiplexed methylation technique, for tumor suppressors in bladder cancer and body fluids. Methylation profiles of tumor suppressor genes were clinically relevant for histopathological stratification of bladder tumors and offered a noninvasive diagnostic strategy for the clinical management of patients affected with uroepithelial neoplasias. PMID:21227392

  8. Proteomic profiling of human plasma for cancer biomarker discovery.

    PubMed

    Huang, Zhao; Ma, Linguang; Huang, Canhua; Li, Qifu; Nice, Edouard C

    2017-03-01

    Over the past decades, substantial advances have been made in both the early diagnosis and accurate prognosis of many cancers because of the impressive development of novel proteomic strategies. However, it remains difficult to standardize proteomic approaches. In addition, the heterogeneity of proteins in distinct tissues results in incomplete population of the whole proteome, which inevitably limits its clinical practice. As one of the most complex proteomes in the human body, the plasma proteome contains secreted proteins originating from multiple organs and tissues, making it a favorable matrix for comprehensive biomarker discovery. Here, we will discuss the roles of plasma proteome profiling in cancer biomarker discovery and validation, and highlight both the inherent advantages and disadvantages. Although several hurdles lay ahead, further advances in this technology will greatly increase our understanding of cancer biology, reveal new biomarkers and biomarker panels, and open a new avenue for more efficient early diagnosis and surveillance of cancer, leading toward personalized medicine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Personalized chemotherapy selection for breast cancer using gene expression profiles

    PubMed Central

    Yu, Kaixian; Sang, Qing-Xiang Amy; Lung, Pei-Yau; Tan, Winston; Lively, Ty; Sheffield, Cedric; Bou-Dargham, Mayassa J.; Liu, Jun S.; Zhang, Jinfeng

    2017-01-01

    Choosing the optimal chemotherapy regimen is still an unmet medical need for breast cancer patients. In this study, we reanalyzed data from seven independent data sets with totally 1079 breast cancer patients. The patients were treated with three different types of commonly used neoadjuvant chemotherapies: anthracycline alone, anthracycline plus paclitaxel, and anthracycline plus docetaxel. We developed random forest models with variable selection using both genetic and clinical variables to predict the response of a patient using pCR (pathological complete response) as the measure of response. The models were then used to reassign an optimal regimen to each patient to maximize the chance of pCR. An independent validation was performed where each independent study was left out during model building and later used for validation. The expected pCR rates of our method are significantly higher than the rates of the best treatments for all the seven independent studies. A validation study on 21 breast cancer cell lines showed that our prediction agrees with their drug-sensitivity profiles. In conclusion, the new strategy, called PRES (Personalized REgimen Selection), may significantly increase response rates for breast cancer patients, especially those with HER2 and ER negative tumors, who will receive one of the widely-accepted chemotherapy regimens. PMID:28256629

  10. Caregiver Activation and Home Hospice Nurse Communication in Advanced Cancer Care.

    PubMed

    Dingley, Catherine E; Clayton, Margaret; Lai, Djin; Doyon, Katherine; Reblin, Maija; Ellington, Lee

    Activated patients have the skills, knowledge, and confidence to manage their care, resulting in positive outcomes such as lower hospital readmission and fewer adverse consequences due to poor communication with providers. Despite extensive evidence on patient activation, little is known about activation in the home hospice setting, when family caregivers assume more responsibility in care management. We examined caregiver and nurse communication behaviors associated with caregiver activation during home hospice visits of patients with advanced cancer using a prospective observational design. We adapted Street's Activation Verbal Coding tool to caregiver communication and used qualitative thematic analysis to develop codes for nurse communications that preceded and followed each activation statement in 60 audio-recorded home hospice visits. Caregiver communication that reflected activation included demonstrating knowledge regarding the patient/care, describing care strategies, expressing opinions regarding care, requesting explanations of care, expressing concern about the patient, and redirecting the conversation toward the patient. Nurses responded by providing education, reassessing the patient/care environment, validating communications, clarifying care issues, updating/revising care, and making recommendations for future care. Nurses prompted caregiver activation through focused care-specific questions, open-ended questions/statements, and personal questions. Few studies have investigated nurse/caregiver communication in home hospice, and, to our knowledge, no other studies focused on caregiver activation. The current study provides a foundation to develop a framework of caregiver activation through enhanced communication with nurses. Activated caregivers may facilitate patient-centered care through communication with nurses in home hospice, thus resulting in enhanced outcomes for patients with advanced cancer.

  11. Acute hospital admission for nursing home residents without cognitive impairment with a diagnosis of cancer.

    PubMed

    Drageset, J; Eide, G E; Harrington, C; Ranhoff, A H

    2015-03-01

    Studies of hospitalisation of cognitively intact nursing home (NH) residents with cancer are scarce. Knowledge about associations between socio-demographic, medical and social support variables and hospital admissions aids in preventing unnecessary admissions. This is part of a prospective study from 2004 to 2005 with follow-up to 2010 for admission rates. We studied whether residents with cancer have more admissions and whether socio-demographic and medical variables and social support subdimensions are associated with admission among cognitively intact NH residents with (n = 60) and without (n = 167) cancer aged ≥65 years scoring ≤0.5 on the Clinical Dementia Rating Scale and residing ≥6 months. We measured social support by face-to-face interview. We identified all respondents through NH medical records for hospital admission, linking their identification numbers to the hospital record system to register all admissions. We examined whether socio-demographic and medical variables (medical records) and social support subscales were associated with the time between inclusion and first admission. Residents with cancer had more admissions (25/60) than those without (53/167) (odds ratio 1.7). Social integration was correlated with admission (P = 0.04) regardless of cancer diagnosis. Residents with cancer had more hospital admissions than those without. Higher social integration gave more admissions independent of cancer diagnosis.

  12. Cancer patients' willingness to pay for blood transfusions at home: results from a contingent valuation study in a French cancer network.

    PubMed

    Havet, Nathalie; Morelle, Magali; Remonnay, Raphaël; Carrere, Marie-Odile

    2012-06-01

    Home blood transfusion may be an interesting alternative to hospital transfusion, especially when given with curative or palliative intent or for terminal care in advanced-stage cancer patients. However, there is limited information about patients' attitude toward this type of care. The purpose of this study was to measure French cancer patients' willingness to pay (WTP) for home blood transfusion and to analyze determinants of their choice. A contingent valuation survey was administered to 139 patients receiving transfusions in the framework of a regional home care network or in the hospital outpatient department. Participation was high (90%). Most patients (65%) had received home care, including 43% blood transfusions. Just under half of the patients gave a zero WTP, among which we identified 8 protest bidders. The median WTP for home blood transfusion was 26.5 per patient. In multivariate analysis, long home-hospital distance, poor quality of life, and previous experience of home care were identified as important factors in determining how much more patients would be willing to pay for transfusion at home. These results demonstrate the benefits of developing domiciliary services to improve patient well-being, notably for the weakest among them. The significant impact of previous home care experience on WTP is probably related to the strong involvement of physicians from the blood center and to their active contribution to a high-level homecare network. Some of our findings could be useful for policy decision-making regarding home care.

  13. Dealing with chemotherapy-related symptoms at home: a qualitative study in adult patients with cancer.

    PubMed

    Coolbrandt, A; Dierckx de Casterlé, B; Wildiers, H; Aertgeerts, B; Van der Elst, E; van Achterberg, T; Milisen, K

    2016-01-01

    Given that chemotherapy treatments are done mostly in an outpatient setting, patients with cancer must deal with treatment-related symptoms mainly at home. Evidence suggests that they often feel left alone or unprepared to do so. This qualitative study explores how patients deal with chemotherapy-related symptoms in their home, which factors and ideas influence their self-management and what role professional caregivers play. One-off, semi-structured interviews were held with 28 adult patients with cancer being treated with chemotherapy. Using a Grounded Theory approach, we cyclically collected and analysed data to come to a thorough understanding of the major conceptual themes and their interconnections. Dealing with chemotherapy-related symptoms involves a process of experiencing and learning how side effects unfold over time and how to deal with them. Patients express very personal symptom experiences and symptom-management styles, which are shaped by personal factors (e.g. coping with cancer and cancer treatment, perceived level of control) and environmental factors (e.g. professionals' attitude, information resources). Improving symptom self-management support requires active exploration of the personal symptom experience and symptom-management style. Professional care should be tailored to the patient's perspective and should address personal and environmental determinants of their behaviour.

  14. Managing Medications During Home Hospice Cancer Care: The Needs of Family Caregivers

    PubMed Central

    Tjia, Jennifer; Ellington, Lee; Clayton, Margaret F.; Lemay, Celeste; Reblin, Maija

    2015-01-01

    Context Family caregivers (FCGs) are often at the frontline of symptom management for patients with advanced illness in home hospice. FCGs’ cognitive, social and technical skills in complex medication management have been well studied in the literature; however, few studies have tested existing frameworks in clinical cases in home hospice. Objectives This study sought to assess the applicability of Lau et al.’s caregiver medication management skills framework in the context of family caregiving in home hospice in order to further the understanding of FCGs’ essential medication management skills. Methods This was a secondary data analysis of 18 audio recorded home hospice visits transcribed verbatim; deductive content analysis of caregiver-nurse interactions was conducted. The target sample included FCGs of hospice patients who had cancer diagnoses in hospices located in the greater urban area of the Rocky Mountain West. Caregiver medication management skills were identified and categorized into the five domains of caregiver expertise. Exemplars of each domain were identified. Results An average of four medications (SD 3.5) was discussed at each home hospice visit. Medication knowledge skills were observed in the majority of home hospice visits (15 of 18). Teamwork skills were observed in 11 of 18 cases, followed by organizational and personhood skills (10 of 18). Symptom management skills occurred in 12 of 18 cases. An additional two subconstructs of the Personhood domain –1) advocacy for the caregiver and 2) skills in discontinuing medications – were proposed. Conclusion These findings support Lau et al.’s framework for caregiver medication management skills and expands upon the existing domains proposed. Future interventions to assess FCGs’ skills are recommended. PMID:26159294

  15. Managing Medications During Home Hospice Cancer Care: The Needs of Family Caregivers.

    PubMed

    Tjia, Jennifer; Ellington, Lee; Clayton, Margaret F; Lemay, Celeste; Reblin, Maija

    2015-11-01

    Family caregivers (FCGs) are often at the frontline of symptom management for patients with advanced illness in home hospice. FCGs' cognitive, social, and technical skills in complex medication management have been well studied in the literature; however, few studies have tested existing frameworks in clinical cases in home hospice. This study sought to assess the applicability of caregiver medication management skills framework by Lau et al. in the context of family caregiving in home hospice to further the understanding of FCGs' essential medication management skills. This was a secondary data analysis of 18 audio recorded home hospice visits transcribed verbatim; deductive content analysis of caregiver-nurse interactions was conducted. The target sample included FCGs of hospice patients who had cancer diagnoses in hospices located in the greater urban area of the Rocky Mountain West. Caregiver medication management skills were identified and categorized into the five domains of caregiver expertise. Exemplars of each domain were identified. An average of four medications (SD = 3.5) was discussed at each home hospice visit. Medication knowledge skills were observed in most home hospice visits (15 of 18). Teamwork skills were observed in 11 of 18 cases, followed by organizational and personhood skills (10 of 18). Symptom management skills occurred in 12 of 18 cases. An additional two subconstructs of the personhood domain-1) advocacy for the caregiver and 2) skills in discontinuing medications-were proposed. These findings support framework by Lau et al. for caregiver medication management skills and expands on the existing domains proposed. Future interventions to assess FCGs' skills are recommended. Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  16. Micro-RNA profiling in kidney and bladder cancers.

    PubMed

    Gottardo, Fedra; Liu, Chang Gong; Ferracin, Manuela; Calin, George A; Fassan, Matteo; Bassi, Pierfrancesco; Sevignani, Cinzia; Byrne, Dolores; Negrini, Massimo; Pagano, Francesco; Gomella, Leonard G; Croce, Carlo M; Baffa, Raffaele

    2007-01-01

    Micro-RNAs are a group of small noncoding RNAs with modulator activity of gene expression. Recently, micro-RNA genes were found abnormally expressed in several types of cancers. To study the role of the micro-RNAs in human kidney and bladder cancer, we analyzed the expression profile of 245 micro-RNAs in kidney and bladder primary tumors. A total of 27 kidney specimens (20 carcinomas, 4 benign renal tumors, and 3 normal parenchyma) and 27 bladder specimens (25 urothelial carcinomas and 2 normal mucosa) were included in the study. Total RNA was used for hybridization on an oligonucleotide microchip for micro-RNA profiling developed in our laboratories. This microchip contains 368 probes in triplicate, corresponding to 245 human and mouse micro-RNA genes. A set of 4 human micro-RNAs (miR-28, miR-185, miR-27, and let-7f-2) were found significantly up-regulated in renal cell carcinoma (P < 0.05) compared to normal kidney. Human micro-RNAs miR-223, miR-26b, miR-221, miR-103-1, miR-185, miR-23b, miR-203, miR-17-5p, miR-23a, and miR-205 were significantly up-regulated in bladder cancers (P < 0.05) compared to normal bladder mucosa. Of the kidney cancers studied, there was no differential micro-RNA expression across various stages, whereas with increasing tumor-nodes-metastasis staging in bladder cancer, miR-26b showed a moderate decreasing trend (P = 0.082). Our results show that different micro-RNAs are deregulated in kidney and bladder cancer, suggesting the involvement of these genes in the development and progression of these malignancies. Further studies are needed to clarify the role of micro-RNAs in neoplastic transformation and to test the potential clinical usefulness of micro-RNAs microarrays as diagnostic and prognostic tool.

  17. Colorectal cancer detection using targeted serum metabolic profiling.

    PubMed

    Zhu, Jiangjiang; Djukovic, Danijel; Deng, Lingli; Gu, Haiwei; Himmati, Farhan; Chiorean, E Gabriela; Raftery, Daniel

    2014-09-05

    Colorectal cancer (CRC) is one of the most prevalent and deadly cancers in the world. Despite an expanding knowledge of its molecular pathogenesis during the past two decades, robust biomarkers to enable screening, surveillance, and therapy monitoring of CRC are still lacking. In this study, we present a targeted liquid chromatography-tandem mass spectrometry-based metabolic profiling approach for identifying biomarker candidates that could enable highly sensitive and specific CRC detection using human serum samples. In this targeted approach, 158 metabolites from 25 metabolic pathways of potential significance were monitored in 234 serum samples from three groups of patients (66 CRC patients, 76 polyp patients, and 92 healthy controls). Partial least-squares-discriminant analysis (PLS-DA) models were established, which proved to be powerful for distinguishing CRC patients from both healthy controls and polyp patients. Receiver operating characteristic curves generated based on these PLS-DA models showed high sensitivities (0.96 and 0.89, respectively, for differentiating CRC patients from healthy controls or polyp patients), good specificities (0.80 and 0.88), and excellent areas under the curve (0.93 and 0.95). Monte Carlo cross validation was also applied, demonstrating the robust diagnostic power of this metabolic profiling approach.

  18. Tumour homing peptide-functionalized porous silicon nanovectors for cancer therapy.

    PubMed

    Kinnari, Päivi J; Hyvönen, Maija L K; Mäkilä, Ermei M; Kaasalainen, Martti H; Rivinoja, Antti; Salonen, Jarno J; Hirvonen, Jouni T; Laakkonen, Pirjo M; Santos, Hélder A

    2013-12-01

    Tumour targeting nanoparticles (NPs) have demonstrated great potential for enhancing anticancer drug delivery to tumour sites and for reducing the side effects of chemotherapy. However, many nanoparticulate delivery systems still lack efficient tumour accumulation. In this work, we present a porous silicon (PSi) nanovector functionalized with a tumour-homing peptide, which targets the mammary-derived growth inhibitor (MDGI) expressing cancer cells both in vitro and in vivo, thereby enhancing the accumulation of the NPs in the tumours. We demonstrated that the tumour homing peptide (herein designated as CooP) functionalized thermally hydrocarbonized PSi (THCPSi) NPs homed specifically to the subcutaneous MDGI-expressing xenograft tumours. The THCPSi-CooP NPs were stable in human plasma and their uptake by MDGI-expressing cancer cells measured by confocal microscopy and flow cytometry was significantly increased compared to the non-functionalized THCPSi NPs. After intravenous injections into nude mice bearing MDGI-expressing tumours, effective targeting was detected and THCPSi-CooP NPs showed ~9-fold higher accumulation in the tumour site compared to the control THCPSi NPs. Accumulation of both NPs in the vital organs was negligible. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Improving sleep quality for cancer patients: benefits of a home-based exercise intervention.

    PubMed

    Tang, Mei-Feng; Liou, Tsan-Hon; Lin, Chia-Chin

    2010-10-01

    1) To determine the effect of a home-based walking exercise program on the sleep quality and quality of life of cancer patients, as well as 2) to determine if enhanced sleep quality was associated with improvement in quality of life over time. This is a prospective, longitudinal, two-armed, randomized clinical trial. Participants were recruited from oncology outpatient clinics in two university-based medical centers and were allocated to either usual care (n = 35) or a home-based walking exercise intervention for 8 weeks (n = 36). Measurements included the Taiwanese version of the Pittsburgh Sleep Quality Index, the Medical Outcomes Study Short Form-36, the Taiwanese Version Ratings of the Perceived Exertion Scale, and a walking exercise log. This study was analyzed on an intention-to-treat basis. Effects of the walking exercise program on sleep quality and quality of life were analyzed by the generalized estimating equation method. Patients in the exercise group reported significant improvements in sleep quality (beta = -3.54, p < 0.01) and the mental health dimension of quality of life (beta = 10.48, p < 0.01). Among patients who exercised, enhanced sleep quality also corresponded with reduced bodily pain (beta = 0.98, p = 0.04) and improvements over time in the mental health dimension of quality of life (beta = -3.87, p < 0.01). A home-based walking exercise program can be easily incorporated into care for cancer patients who are suffering from sleep disturbances.

  20. Proteome profiling of breast cancer biopsies reveals a wound healing signature of cancer-associated fibroblasts.

    PubMed

    Groessl, Michael; Slany, Astrid; Bileck, Andrea; Gloessmann, Kerstin; Kreutz, Dominique; Jaeger, Walter; Pfeiler, Georg; Gerner, Christopher

    2014-11-07

    Breast cancer is still the most common type of cancer in women; an important role in carcinogenesis is actually attributed to cancer-associated fibroblasts. In this study, we investigated whether it is possible to assess the functional state of cancer-associated fibroblasts through tumor tissue proteome profiling. Tissue proteomics was performed on tumor-central, tumor-near, and tumor-distant biopsy sections from breast adenocarcinoma patients, which allowed us to identify 2074 proteins. Data were interpreted referring to reference proteome profiles generated from primary human mammary fibroblasts comprising 4095 proteins. These cells were analyzed in quiescent cell state as well as after in vitro treatment with TGFβ or IL-1β, stimulating wound healing or inflammatory processes, respectively. Representative for cancer cells, we investigated the mammary carcinoma cell line ZR-75-1, identifying 5212 proteins. All mass analysis data have been made fully accessible via ProteomeXchange, DOI PXD001311 and PXD001323-8. Comparison of tissue proteomics data with all of those reference profiles revealed predominance of cancer cell-derived proteins within the tumor and fibroblast-derived proteins in the tumor-distant tissue sections. Remarkably, proteins characteristic for acute inflammation were hardly identified in the tissue samples. In contrast, several proteins found by us to be induced by TGFβ in mammary fibroblasts, including fibulin-5, SLC2A1, and MUC18, were positively identified in all tissue samples, with relatively higher abundance in tumor neighboring tissue sections. These findings indicate a predominance of cancer-associated fibroblasts with wound healing activities localized around tumors.

  1. Mutational Profile of Metastatic Breast Cancers: A Retrospective Analysis

    PubMed Central

    Pedrero, Marion; Campone, Mario; Soria, Jean-Charles; Massard, Christophe; Lévy, Christelle; Arnedos, Monica; Lacroix-Triki, Magali; Garrabey, Julie; Boursin, Yannick; Deloger, Marc; Commo, Frédéric; Scott, Véronique; Kamal, Maud; Diéras, Véronique; Gonçalves, Anthony; Romieu, Gilles; Vanlemmens, Laurence; Mouret Reynier, Marie-Ange; Théry, Jean-Christophe; Le Du, Fanny; Guiu, Séverine; Dalenc, Florence; Bonnefoi, Hervé; Jimenez, Marta; Le Tourneau, Christophe; André, Fabrice

    2016-01-01

    Background Major advances have been achieved in the characterization of early breast cancer (eBC) genomic profiles. Metastatic breast cancer (mBC) is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing. Methods and Findings Whole-exome sequencing was performed on 216 tumor–blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO) prospective trials. Mutational profiles from 772 primary breast tumors from The Cancer Genome Atlas (TCGA) were used as a reference for comparing primary and mBC mutational profiles. Twelve genes (TP53, PIK3CA, GATA3, ESR1, MAP3K1, CDH1, AKT1, MAP2K4, RB1, PTEN, CBFB, and CDKN2A) were identified as significantly mutated in mBC (false discovery rate [FDR] < 0.1). Eight genes (ESR1, FSIP2, FRAS1, OSBPL3, EDC4, PALB2, IGFN1, and AGRN) were more frequently mutated in mBC as compared to eBC (FDR < 0.01). ESR1 was identified both as a driver and as a metastatic gene (n = 22, odds ratio = 29, 95% CI [9–155], p = 1.2e-12) and also presented with focal amplification (n = 9) for a total of 31 mBCs with either ESR1 mutation or amplification, including 27 hormone receptor positive (HR+) and HER2 negative (HER2−) mBCs (19%). HR+/HER2− mBC presented a high prevalence of mutations on genes located on the mechanistic target of rapamycin (mTOR) pathway (TSC1 and TSC2) as compared to HR+/HER2− eBC (respectively 6% and 0.7%, p = 0.0004). Other actionable genes were more frequently mutated in HR+ mBC, including ERBB4 (n = 8), NOTCH3 (n = 7), and ALK (n = 7). Analysis of mutational signatures revealed a significant increase in APOBEC-mediated mutagenesis in HR+/HER2− metastatic tumors as compared to primary TCGA samples (p < 2e-16). The main limitations of this study include the absence of bone

  2. Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

    NASA Astrophysics Data System (ADS)

    Balivada, Sivasai

    Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V

  3. Blood Gene Expression Profiling of Breast Cancer Survivors Experiencing Fibrosis

    SciTech Connect

    Landmark-Hoyvik, Hege; Dumeaux, Vanessa; Reinertsen, Kristin V.; Edvardsen, Hege; Fossa, Sophie D.; Borresen-Dale, Anne-Lise

    2011-03-01

    Purpose: To extend knowledge on the mechanisms and pathways involved in maintenance of radiation-induced fibrosis (RIF) by performing gene expression profiling of whole blood from breast cancer (BC) survivors with and without fibrosis 3-7 years after end of radiotherapy treatment. Methods and Materials: Gene expression profiles from blood were obtained for 254 BC survivors derived from a cohort of survivors, treated with adjuvant radiotherapy for breast cancer 3-7 years earlier. Analyses of transcriptional differences in blood gene expression between BC survivors with fibrosis (n = 31) and BC survivors without fibrosis (n = 223) were performed using R version 2.8.0 and tools from the Bioconductor project. Gene sets extracted through a literature search on fibrosis and breast cancer were subsequently used in gene set enrichment analysis. Results: Substantial differences in blood gene expression between BC survivors with and without fibrosis were observed, and 87 differentially expressed genes were identified through linear analysis. Transforming growth factor-{beta}1 signaling was identified as the most significant gene set, showing a down-regulation of most of the core genes, together with up-regulation of a transcriptional activator of the inhibitor of fibrinolysis, Plasminogen activator inhibitor 1 in the BC survivors with fibrosis. Conclusion: Transforming growth factor-{beta}1 signaling was found down-regulated during the maintenance phase of fibrosis as opposed to the up-regulation reported during the early, initiating phase of fibrosis. Hence, once the fibrotic tissue has developed, the maintenance phase might rather involve a deregulation of fibrinolysis and altered degradation of extracellular matrix components.

  4. Next-generation tag sequencing for cancer gene expression profiling.

    PubMed

    Morrissy, A Sorana; Morin, Ryan D; Delaney, Allen; Zeng, Thomas; McDonald, Helen; Jones, Steven; Zhao, Yongjun; Hirst, Martin; Marra, Marco A

    2009-10-01

    We describe a new method, Tag-seq, which employs ultra high-throughput sequencing of 21 base pair cDNA tags for sensitive and cost-effective gene expression profiling. We compared Tag-seq data to LongSAGE data and observed improved representation of several classes of rare transcripts, including transcription factors, antisense transcripts, and intronic sequences, the latter possibly representing novel exons or genes. We observed increases in the diversity, abundance, and dynamic range of such rare transcripts and took advantage of the greater dynamic range of expression to identify, in cancers and normal libraries, altered expression ratios of alternative transcript isoforms. The strand-specific information of Tag-seq reads further allowed us to detect altered expression ratios of sense and antisense (S-AS) transcripts between cancer and normal libraries. S-AS transcripts were enriched in known cancer genes, while transcript isoforms were enriched in miRNA targeting sites. We found that transcript abundance had a stronger GC-bias in LongSAGE than Tag-seq, such that AT-rich tags were less abundant than GC-rich tags in LongSAGE. Tag-seq also performed better in gene discovery, identifying >98% of genes detected by LongSAGE and profiling a distinct subset of the transcriptome characterized by AT-rich genes, which was expressed at levels below those detectable by LongSAGE. Overall, Tag-seq is sensitive to rare transcripts, has less sequence composition bias relative to LongSAGE, and allows differential expression analysis for a greater range of transcripts, including transcripts encoding important regulatory molecules.

  5. Integrative radiogenomic profiling of squamous cell lung cancer

    PubMed Central

    Abazeed, Mohamed E.; Adams, Drew J.; Hurov, Kristen E.; Tamayo, Pablo; Creighton, Chad J.; Sonkin, Dmitriy; Giacomelli, Andrew O.; Du, Charles; Fries, Daniel F.; Wong, Kwok-Kin; Mesirov, Jill P.; Loeffler, Jay S.; Schreiber, Stuart L.; Hammerman, Peter S.; Meyerson, Matthew

    2013-01-01

    Radiation therapy is one of the mainstays of anti-cancer treatment, but the relationship between the radiosensitivity of cancer cells and their genomic characteristics is still not well-defined. Here we report the development of a high-throughput platform for measuring radiation survival in vitro and its validation by comparison to conventional clonogenic radiation survival analysis. We combined results from this high-throughput assay with genomic parameters in cell lines from squamous cell lung carcinoma, which is standardly treated by radiation therapy, to identify parameters that predict radiation sensitivity. We showed that activation of NFE2L2, a frequent event in lung squamous cancers, confers radiation resistance. An expression-based, in silico screen nominated inhibitors of PI3K as NFE2L2 antagonists. We showed that the selective PI3K inhibitor, NVP-BKM120, both decreased NRF2 protein levels and sensitized NFE2L2 or KEAP1 mutant cells to radiation. We then combined results from this high-throughput assay with single-sample gene set enrichment analysis (ssGSEA) of gene expression data. The resulting analysis identified pathways implicated in cell survival, genotoxic stress, detoxification, and innate and adaptive immunity as key correlates of radiation sensitivity. The integrative, high-throughput methods shown here for large-scale profiling of radiation survival and genomic features of solid-tumor derived cell lines should facilitate tumor radiogenomics and the discovery of genotype-selective radiation sensitizers and protective agents. PMID:23980093

  6. Genetic profiling to predict recurrence of early cervical cancer.

    PubMed

    Lee, Yoo-Young; Kim, Tae-Joong; Kim, Ji-Young; Choi, Chel Hun; Do, In-Gu; Song, Sang Yong; Sohn, Insuk; Jung, Sin-Ho; Bae, Duk-Soo; Lee, Jeong-Won; Kim, Byoung-Gie

    2013-12-01

    Recurrence is the major cause of death in early cervical cancer. We compared the prediction powers for disease recurrence between the gene set prognostic model and the clinical prognostic model. A gene set model to predict disease free survival was developed using the cDNA-mediated annealing, selection, extension, and ligation (DASL) assay data set from a cohort of early cervical cancer patients who had been treated with radical surgery with or without adjuvant therapy. A clinical prediction model was also developed using the same cohort, and the ability of predicting recurrence from each model was compared. Adequate DASL assay profiles were obtained from 300 patients, and we selected 12 genes for the gene set model. When patients were categorized as having a low or high risk by the prognostic score, the Kaplan-Meier curve showed significantly different recurrence rates between the two groups. The clinical model was developed using FIGO stage and post-surgical pathological findings. In multivariate Cox regression analysis of prognostic models, the gene set prognostic model showed a higher hazard ratio than that of the clinical prognostic model. The genetic quantitative approach may be better in predicting recurrence in early cervical cancer patients. © 2013 Elsevier Inc. All rights reserved.

  7. miRNA expression profile in multicellular breast cancer spheroids.

    PubMed

    Mandujano-Tinoco, Edna Ayerim; Garcia-Venzor, Alfredo; Muñoz-Galindo, Laura; Lizarraga-Sanchez, Floria; Favela-Orozco, Andrei; Chavez-Gutierrez, Edwin; Krötzsch, Edgar; Salgado, Rosa M; Melendez-Zajgla, Jorge; Maldonado, Vilma

    2017-10-01

    Multicellular Tumor Spheroids develop a heterogeneous micromilieu and different cell populations, thereby constituting a cancer model with intermediate characteristics between in vitro bi-dimensional cultures and in vivo tumors. Multicellular Tumor Spheroids also acquire tumor aggressiveness features due to transcription modulation of coding and non-coding RNA. Utilizing microarray analyses, we evaluated the microRNAs expression profile in MCF-7 breast cancer cells cultured as Multicellular Tumor Spheroids. The expression data was used to predict associated cellular and molecular functions using different software tools. The biological importance of two dysregulated miRNAs (miR-221-3p and miR-187) was studied by functional assays. Finally, the clinical relevance of these dysregulated miRNAs was explored using previously reported data. Thirty-three dysregulated microRNAs were found in MCF-7 Multicellular Tumor Spheroids. miRNA expression changes were closely linked with growth, proliferation, and cell development. miRNA-221-3p and miR-187 were implicated in the acquisition of migration/invasion capacities, sensitivity to the deprivation of growth factors, cell cycle phase regulation, and cell death. A panel of 5 miRNAs, including miR-187, showed a good predictive value in discriminating between low and high-risk groups of breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Spouse cancer caregivers' burden and distress at entry to home hospice: The role of relationship quality.

    PubMed

    Reblin, Maija; Donaldson, Gary; Ellington, Lee; Mooney, Kathi; Caserta, Michael; Lund, Dale

    2016-08-01

    High-quality relationships may be protective for family caregivers. This study focuses on relationship quality categories (supportive and ambivalent) in spouse caregivers in cancer home hospice. The goals of this article are to, first, describe relationship quality categories among end-of-life caregivers and, second, test the effects of relationship quality categories on caregiver burden and distress within a stress process model. Using questionnaire data collected at entry to home hospice, we found relationship quality categories were proportionally similar to those seen in noncaregiver older adults. Relationship quality significantly predicted caregiver burden, which completely mediated the relationship between caregiver relationship quality and distress. Caregivers whose social contexts place them at risk for greater distress may benefit from increased clinical attention or intervention.

  9. Androgen deprivation modulates gene expression profile along prostate cancer progression.

    PubMed

    Volante, Marco; Tota, Daniele; Giorcelli, Jessica; Bollito, Enrico; Napoli, Francesca; Vatrano, Simona; Buttigliero, Consuelo; Molinaro, Luca; Gontero, Paolo; Porpiglia, Francesco; Tucci, Marcello; Papotti, Mauro; Berruti, Alfredo; Rapa, Ida

    2016-10-01

    Androgen deprivation therapy (ADT) is the standard of care for metastatic prostate cancer and initially induces tumor regression, but invariably results in castration-resistant prostate cancer through various mechanisms, incompletely discovered. Our aim was to analyze the dynamic modulation, determined by ADT, of the expression of selected genes involved in the pathogenesis and progression of prostate cancer (TMPRSS2:ERG, WNT11, SPINK1, CHGA, AR, and SPDEF) using real-time polymerase chain reaction in a series of 59 surgical samples of prostate carcinomas, including 37 cases preoperatively treated with ADT and 22 untreated cases, and in 43 corresponding biopsies. The same genes were analyzed in androgen-deprived and control LNCaP cells. Three genes were significantly up-modulated (WNT11 and AR) or down-modulated (SPDEF) in patients treated with ADT versus untreated cases, as well as in androgen-deprived LNCaP cells. The effect of ADT on CHGA gene up-modulation was almost exclusively detected in cases positive for the TMPRSS2:ERG fusion. The correlation between biopsy and surgical samples was poor for most of the tested genes. Gene expression analysis of separate tumor areas from the same patient showed an extremely heterogeneous profile in the 6 tested cases (all untreated). In conclusion, our results strengthened the implication of ADT in promoting a prostate cancer aggressive phenotype and identified potential biomarkers, with special reference to the TMPRSS2:ERG fusion, which might favor the development of neuroendocrine differentiation in hormone-treated patients. However, intratumoral heterogeneity limits the use of gene expression analysis as a potential prognostic or predictive biomarker in patients treated with ADT.

  10. MicroRNA Profiles Discriminate among Colon Cancer Metastasis

    PubMed Central

    Drusco, Alessandra; Nuovo, Gerard J.; Zanesi, Nicola; Di Leva, Gianpiero; Pichiorri, Flavia; Volinia, Stefano; Fernandez, Cecilia; Antenucci, Anna; Costinean, Stefan; Bottoni, Arianna; Rosito, Immacolata A.; Liu, Chang-Gong; Burch, Aaron; Acunzo, Mario; Pekarsky, Yuri; Alder, Hansjuerg; Ciardi, Antonio; Croce, Carlo M.

    2014-01-01

    MicroRNAs are being exploited for diagnosis, prognosis and monitoring of cancer and other diseases. Their high tissue specificity and critical role in oncogenesis provide new biomarkers for the diagnosis and classification of cancer as well as predicting patients' outcomes. MicroRNAs signatures have been identified for many human tumors, including colorectal cancer (CRC). In most cases, metastatic disease is difficult to predict and to prevent with adequate therapies. The aim of our study was to identify a microRNA signature for metastatic CRC that could predict and differentiate metastatic target organ localization. Normal and cancer tissues of three different groups of CRC patients were analyzed. RNA microarray and TaqMan Array analysis were performed on 66 Italian patients with or without lymph nodes and/or liver recurrences. Data obtained with the two assays were analyzed separately and then intersected to identify a primary CRC metastatic signature. Five differentially expressed microRNAs (hsa-miR-21, -103, -93, -31 and -566) were validated by qRT-PCR on a second group of 16 American metastatic patients. In situ hybridization was performed on the 16 American patients as well as on three distinct commercial tissues microarray (TMA) containing normal adjacent colon, the primary adenocarcinoma, normal and metastatic lymph nodes and liver. Hsa-miRNA-21, -93, and -103 upregulation together with hsa-miR-566 downregulation defined the CRC metastatic signature, while in situ hybridization data identified a lymphonodal invasion profile. We provided the first microRNAs signature that could discriminate between colorectal recurrences to lymph nodes and liver and between colorectal liver metastasis and primary hepatic tumor. PMID:24921248

  11. [Gastric cancer: epidemiologic profile 2001-2007 in Lima, Peru].

    PubMed

    Chirinos, Jesús L; Carbajal, Luz A; Segura, María D; Combe, J; Akiba, S

    2012-01-01

    To describe and compare the demographic and social characteristics as well as lifestyles of patients with gastric cancer against patients with other important gastric disorders, who attended at main reference health services in Lima, Peru. Case control study, matched by sex and age + 2 years, applying a questionnaire to 96 cases with gastric cancer, and to 96 controls from September 2001 to November 2007. There were no significant differences about ethnicity; marital status; exposure to minerals, wood, and metal dusts; tobacco and alcohol; red meat consumption; salt addition; food temperature. 87, 5% of the control group had lesions in the gastric antrum, and 73% of cases group had a tubular adenocarcinoma (56%) in the gastric antrum. There was no family history of cancer in 85% patients of cases group and 59% of controls, (with significant difference). There were significant differences in low scholarship level of cases, as well as for their mothers and fathers (OR 3.75, 3.9, and 3.49 respectively), fruit or vegetables intake, milk or cheese consumption (minus of once a day) (OR 2, 3, 2, 57 and 2, 9 respectively), type of fuel for cooking (firewood, charcoal, and kerosene OR 5, 25), lack of use of refrigerator (OR 8, 4). The profile of a gastric cancer patient was to proceed from the Andean zone (high altitude +3000 meters over sea level) and jungle, low education level (low socioeconomic level), low consumption of fruits, vegetables and milk, use of firewood, charcoal, or kerosene to cook, and no use of refrigerator. The most frequent histological diagnosis in the case group was tubular adenocarcinoma.

  12. Home-Telemonitoring Lung Cancer Intervention in Appalachia: A Pilot Study

    PubMed Central

    Chen, YJ; Narsavage, GL; Frick, KD; Petitte, TM

    2016-01-01

    Benefits of home-telemonitoring for rural dwelling cancer patients are largely unknown. This study examined the effectiveness of home-telemonitoring surveillance with nurse coaching for self-management to improve lung cancer outcomes in mountainous Appalachia where health care access/ service is limited. This randomized clinical trial pilot study compared patient outcomes for telemonitoring versus routine care. A convenience sample (N = 47) was enrolled/ randomized (Telemonitored: 26/ Control: 21) from a university hospital and cancer center. Physiologic parameters and symptoms were collected in the telemonitored group for two weeks; all participants were studied for 60 days after the index treatment/ discharge. The telemonitored group showed greater improvement for both functional status (Wald X2 = 3.78, p = .05) and quality of life (QOL) (Wald X2 = 7.25, p = .007) from baseline to 60 days post-discharge. Compared to controls, telemonitored patients survived longer; had more scheduled medical visits (96% vs. 75%); made more unplanned calls to doctors/ nurses (32% vs. 30% & 64% vs. 50%); had fewer rehospitalizations (28% vs. 40%); and had more ER utilization (36% vs. 30%). The telemonitored group had relative improvements for health utility (.09 on a scale where 0 = death/ 1= perfect health) and QOL (15 on 0–100 VAS). Differences in health care utilization and cost were not significantly different (p > .05), likely due to the sample size. Telemonitoring group satisfaction with care was high and recommended by patients and caregivers. Results suggest that it is possible to improve patient outcomes with home-telemonitoring for self-management in rural areas. Short-term, telemonitoring-based coaching is feasible and offers a promising option to develop patient self-management knowledge and skills. PMID:28184382

  13. Health Profile of Aging Family Caregivers Supporting Adults with Intellectual and Developmental Disabilities at Home

    ERIC Educational Resources Information Center

    Yamaki, Kiyoshi; Hsieh, Kelly; Heller, Tamar

    2009-01-01

    The health status of 206 female caregivers supporting adults with intellectual and developmental disabilities at home was investigated using objective (i.e., presence of chronic health conditions and activity limitations) and subjective (i.e., self-perceived health status) health measures compared with those of women in the general population in 2…

  14. Health Profile of Aging Family Caregivers Supporting Adults with Intellectual and Developmental Disabilities at Home

    ERIC Educational Resources Information Center

    Yamaki, Kiyoshi; Hsieh, Kelly; Heller, Tamar

    2009-01-01

    The health status of 206 female caregivers supporting adults with intellectual and developmental disabilities at home was investigated using objective (i.e., presence of chronic health conditions and activity limitations) and subjective (i.e., self-perceived health status) health measures compared with those of women in the general population in 2…

  15. [The Home Care Doctor Today is "STRIKE" - Considering Care of Terminal Stage Patients with Cancer through a Case Report].

    PubMed

    Ogihara, Miyoko; Yamaoka, Keita; Fujimaki, Yoko; Watanabe, Mutsuko; Hirohara, Masayoshi; Kushida, Kazuki

    2015-12-01

    Although many patients wish to remain in their familiar home environment while undergoing cancer treatment, many obstacles prevent a patient from receiving cancer care at home. With early-stage cancer, the patients may better accept the diagnosis and have a greater will to fight the illness. However as time proceeds, progression or recurrence of cancer may occur, and eventually, proactive treatments will not be available. This progression results in great physical and mental strain on the patients and their family. At all stages of such progression, opportunities exist for a care provider to assist with overcoming potential obstacles by openly communicating with the patients, talking through the patients' experiences, and understanding their feelings. However, on diagnosis, cancer patients must often face the reality that they have very little time left to live. When transiting medical care from their long-trusted hospital to a home care base, a new physician must be selected and other decisions related to their care must be quickly made. Transferring responsibility to a good home care provider can greatly influence a patient's emotional state. This paper reports one such case in which the patients died in their homes with the best comfort and possible outcome.

  16. [Loco-regional chemotherapy at the outpatient clinic for gastric cancer patients with home enteral nutrition].

    PubMed

    Maruyama, Michio; Nagahama, Takeshi; Sugano, Norihide; Satoh, Eigo; Maruyama, Shouji; Tanami, Hideo; Chiba, Tetsuma; Murakata, Ayano; Mitsuhashi, Yosuke; Uehira, Daisuke; Akazawa, Naoya; Suzuki, Keiichirou

    2011-11-01

    In over the 10 years from 2000-2010, 21 gastric cancer patients received loco-regional chemotherapy with home enteral nutrition (HEN) at an outpatient clinic because of insufficient oral intake. These loco-regional chemotherapy regimens consisted of 5 intra-aortic chemotherapies, 4 hepato-arterial infusions and 12 intra-peritoneal chemotherapies. Five out of 8 cases that had measurable lesions showed PR, and 3 cases revealed PD. The patients received HEN with peptide central formula, 400-1,200 kcal/day in night time. The average duration of HEN was 12.9 months. The post-operative nutritional management was needed for continuation and securing of outpatient chemotherapy. The author reported an experience of the outpatient loco-regional chemotherapy with HEN for the gastric cancer patients who could not eat a sufficient volume of food.

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  18. [Can new molecular profiles in epithelial ovarian cancer modify therapeutics?

    PubMed

    Lavoué, V; Rousselin, A; Delplanque, S; Pinsard, M; Henno, S; Foucher, F; Levêque, J; de la Motte Rouge, T

    2017-02-01

    Epithelial ovarian cancer (EOC) affects 4500 women a year in France, with a survival of 30% at 5 years. Treatment is based on extensive surgery and chemotherapy. Around 15% of EOCs are due to genetic mutation predisposition essentially with mutated BRCA1 and BRCA2 genes. Four histological subtypes are described (serous, endometrioid, and mucinous cells to clear), corresponding to different carcinogenesis and distinct molecular mutations. High-grade serous EOCs have a mutation of the BRCA genes in 20-30% of cases. This mutation causes a deficit of repair by homologous recombination of DNA in case of double strand break, allowing greater sensitivity to platinum salts and the use of PARP inhibitors, a protein involved in the repair of single-strand breaks of DNA. PARP inhibitors have shown efficacy in patients mutated BRCA but this effectiveness remains to be demonstrated in patients without congenital mutation, but with acquired BRCAness profile EOC. The BRCAness profile is defined by a tumor having a defect in DNA repair counterpart (not limited to BRCA mutation). Molecular definition of BRCAness is still not consensual but is necessary for the use of PARP inhibitors. Gene expression analyses have identified four subgroups of high-grade serous CEO: mesenchymal, proliferative, differentiated and immunoreactive. These four subtypes, not mutually exclusive, although correlated with prognosis, are not yet used in clinical routine. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Colon cancer prediction with genetic profiles using intelligent techniques.

    PubMed

    Alladi, Subha Mahadevi; P, Shinde Santosh; Ravi, Vadlamani; Murthy, Upadhyayula Suryanarayana

    2008-01-01

    Micro array data provides information of expression levels of thousands of genes in a cell in a single experiment. Numerous efforts have been made to use gene expression profiles to improve precision of tumor classification. In our present study we have used the benchmark colon cancer data set for analysis. Feature selection is done using t-statistic. Comparative study of class prediction accuracy of 3 different classifiers viz., support vector machine (SVM), neural nets and logistic regression was performed using the top 10 genes ranked by the t-statistic. SVM turned out to be the best classifier for this dataset based on area under the receiver operating characteristic curve (AUC) and total accuracy. Logistic Regression ranks as the next best classifier followed by Multi Layer Perceptron (MLP). The top 10 genes selected by us for classification are all well documented for their variable expression in colon cancer. We conclude that SVM together with t-statistic based feature selection is an efficient and viable alternative to popular techniques.

  20. Cancer patient-centered home care: a new model for health care in oncology

    PubMed Central

    Tralongo, Paolo; Ferraù, Francesco; Borsellino, Nicolò; Verderame, Francesco; Caruso, Michele; Giuffrida, Dario; Butera, Alfredo; Gebbia, Vittorio

    2011-01-01

    Patient-centered home care is a new model of assistance, which may be integrated with more traditional hospital-centered care especially in selected groups of informed and trained patients. Patient-centered care is based on patients’ needs rather than on prognosis, and takes into account the emotional and psychosocial aspects of the disease. This model may be applied to elderly patients, who present comorbid diseases, but it also fits with the needs of younger fit patients. A specialized multidisciplinary team coordinated by experienced medical oncologists and including pharmacists, psychologists, nurses, and social assistance providers should carry out home care. Other professional figures may be required depending on patients’ needs. Every effort should be made to achieve optimal coordination between the health professionals and the reference hospital and to employ shared evidence-based guidelines, which in turn guarantee safety and efficacy. Comprehensive care has to be easily accessible and requires a high level of education and knowledge of the disease for both the patients and their caregivers. Patient-centered home care represents an important tool to improve quality of life and help cancer patients while also being cost effective. PMID:21941445

  1. [Home care for terminal cancer patients from the family and caregiver perspective].

    PubMed

    Ishikawa, Mitsuko; Ogiwara, Miyoko; Yamaoka, Keita; Matsumoto, Ayumi; Fujimaki, Yoko; Watanabe, Mutsuko; Kushida, Kazuki

    2014-12-01

    The progression of home care provision is associated with an increased burden on the family, as patients tend to progressively become more dependent on medicine. In the present case, a family supported a patient by performing medical activities such as taking blood sugar measurements, administering insulin injections, exchanging fluids, managing each tube, handling medical devices, conducting status observations, and attending to emergency calls. Thus, the family caregiver undertakes duties that were previously performed by a nurse and interacts with the various professionals who visit the patient's home daily. Therefore, the caregiver undergoes a considerable amount of stress. Family caregivers with no medical knowledge or nursing experience require plenty of support, in order to fulfill a patient's requirements. The first step is the establishment of trust between the medical professionals and the caregiver. In the present case, because the trust had been established, interprofessional collaboration ensured that the patient received support until the end. Thus, we reported on the perspectives of the family and caregiver on home care for terminal cancer patients.

  2. Oral cancer: the association between nation-based alcohol-drinking profiles and oral cancer mortality.

    PubMed

    Petti, Stefano; Scully, Crispian

    2005-09-01

    The unclear association between different nation-based alcohol-drinking profiles and oral cancer mortality was investigated using, as observational units, 20 countries from Europe, Northern America, Far Eastern Asia, with cross-nationally comparable data. Stepwise multiple regression analyses were run with male age-standardised, mortality rate (ASMR) as explanatory variable and annual adult alcohol consumption, adult smoking prevalence, life expectancy, as explanatory. Large between-country differences in ASMR (range, 0.88-6.87 per 100,000) were found, but the mean value was similar to the global estimate (3.31 vs. 3.09 per 100,000). Differences in alcohol consumption (2.06-21.03 annual litres per capita) and in distribution between beverages were reported. Wine was the most prevalent alcoholic beverage in 45% of cases. Significant increases in ASMR for every litre of pure ethanol (0.15 per 100,000; 95 CI, 0.01-0.29) and spirits (0.26 per 100,000; 95 CI, 0.03-0.49), non-significant effects for beer and wine were estimated. The impact of alcohol on oral cancer deaths would be higher than expected and the drinking profile could affect cancer mortality, probably because of the different drinking pattern of spirit drinkers, usually consuming huge alcohol quantities on single occasions, and the different concentrations of ethanol and cancer-preventing compounds such as polyphenols, in the various beverages.

  3. Clinical profile of Ethiopian patients with breast cancer.

    PubMed

    Gebremedhin, A; Shamebo, M

    1998-11-01

    This prospective study was designed to obtain information on demographic characteristics, clinical profile and problems related to early diagnosis and treatment of breast cancer in 72 Ethiopian patients. There were 62 females and 10 males, the female to male ratio being 6.2:1. The age range of the females was 21-82 (mean 41.8 +/- 12.8) years and that of the males' was 38-75 (mean 52.1 +/- 12.2) years. The time interval between the onset of breast-related symptoms to diagnosis varied from 2-108 (median 12) months. Infiltrating ductal and lobular carcinoma histologic types accounted for 85% and 11%, respectively, in 62 cases who had surgical biopsies. Surgery was performed in 46 cases out of whom only 21 cases received adjuvant treatment. Eighteen females refused mastectomy at some point before they came to our clinic with metastatic disease. After a median follow up duration of 36 (range 2-120) months, 29 cases were alive, 24 died and 19 were lost to follow up. The cause of death in 17 subjects (71%) was rapidly refilling pleural effusion and superimposed infection. Both females and males had similar clinical characteristics, except that, the males were older by 10 years. Moreover, the females in this series developed breast cancer at a younger age (72% were premenopausal) and 76% had advanced disease (Stages III and IV) at presentation, similar to females from other African countries. We suggest that the attitude of Ethiopian females towards breast cancer has to change through continuous but targeted public education.

  4. Progressive lung cancer determined by expression profiling and transcriptional regulation.

    PubMed

    Han, Namshik; Dol, Zulkifli; Vasieva, Olga; Hyde, Russell; Liloglou, Triantafillos; Raji, Olaide; Brambilla, Elisabeth; Brambilla, Christian; Martinet, Yves; Sozzi, Gabriella; Risch, Angela; Montuenga, Luis M; Brass, Andy; Field, John K

    2012-07-01

    Clinically, our ability to predict disease outcome for patients with early stage lung cancer is currently poor. To address this issue, tumour specimens were collected at surgery from non-small cell lung cancer (NSCLC) patients as part of the European Early Lung Cancer (EUELC) consortium. The patients were followed-up for three years post-surgery and patients who suffered progressive disease (PD, tumour recurrence, metastasis or a second primary) or remained disease-free (DF) during follow-up were identified. RNA from both tumour and adjacent-normal lung tissue was extracted from patients and subjected to microarray expression profiling. These samples included 36 adenocarcinomas and 23 squamous cell carcinomas from both PD and DF patients. The microarray data was subject to a series of systematic bioinformatics analyses at gene, network and transcription factor levels. The focus of these analyses was 2-fold: firstly to determine whether there were specific biomarkers capable of differentiating between PD and DF patients, and secondly, to identify molecular networks which may contribute to the progressive tumour phenotype. The experimental design and analyses performed permitted the clear differentiation between PD and DF patients using a set of biomarkers implicated in neuroendocrine signalling and allowed the inference of a set of transcription factors whose activity may differ according to disease outcome. Potential links between the biomarkers, the transcription factors and the genes p21/CDKN1A and Myc, which have previously been implicated in NSCLC development, were revealed by a combination of pathway analysis and microarray meta-analysis. These findings suggest that neuroendocrine-related genes, potentially driven through p21/CDKN1A and Myc, are closely linked to whether or not a NSCLC patient will have poor clinical outcome.

  5. Does dying at home influence the good death of terminal cancer patients?

    PubMed

    Yao, Chien-An; Hu, Wen-Yu; Lai, Yun-Fong; Cheng, Shao-Yi; Chen, Ching-Yu; Chiu, Tai-Yuan

    2007-11-01

    To investigate whether dying at home influences the likelihood that a terminal cancer patient will achieve a good death despite the limited medical resources available in many communities, this study investigated the relationship between the achievement of a good death and the performance of good-death services in two groups with different places of death, and explored the possible factors associated with this relationship. Three hundred and seventy-four consecutive patients with terminal cancers admitted to a palliative care unit were enrolled. Two instruments, the good-death scale and the audit scale for good-death services, were used in the study. Mean age of the 374 patients was 65.45 +/- 14.77 years. The total good-death score in the home-death group (n=307) was significantly higher than that in the hospital-death group (n=67), both at the time of admission (t= -5.741, P<0.001) and prior to death (t= -3.027, P<0.01). However, the score of item "degree of physical comfort" assessed prior to death in the home-death group was lower than that in the hospital-death group (P=0.185). As to the audit scale for good-death services, each subscale score and total scores in the home-death group were significantly higher than that in the hospital-death group, with the exception of the subscale "continuity of social support" (4.72 vs. 4.61, P=0.132). Bereavement support (odds ratio=1.01, 95% confidence interval=0.62-1.39; multiple regression), alleviation of anxiety (0.81, 0.46-1.15), decision-making participation (0.61, 0.26-0.95), fulfillment of last wish (0.45, 0.08-0.82), and survival time (0.00, 0.00-0.01) were independent correlates of the good-death score (35.8% of explained variance). However, the place of death was not in the model. The study conclusively suggests the necessity for palliative home care to strengthen the competence of physical care. Moreover, earlier incorporation of palliative care into anticancer therapies can lead to better death preparation and

  6. Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

    NASA Astrophysics Data System (ADS)

    Ashkani, Jahanshah; Naidoo, Kevin J.

    2016-05-01

    Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.

  7. Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

    DTIC Science & Technology

    2014-12-18

    report will also be included in the comprehensive report to be prepared and submitted by Dr . Steven Dubinett (UCLA) as the Initiating PI...Initiating PI ( Dr . Steve Dubinett) and other Partnering PIs ( Dr . Avrum Spira and Dr . Pierre Massion) we performed RNA-sequencing and microarray profiling of...analysis of the airway Field cancerization in NSCLC. MD Anderson Cancer Center ( Dr . I Wistuba) PROGRESS REPORT Molecular Profiles for Lung Cancer

  8. Interactions of Factors and Profiles of Incontinent Nursing Home Residents and Hospital Patients: A Classification Tree Analysis.

    PubMed

    Mandl, Manuela; Halfens, Ruud J G; Lohrmann, Christa

    2016-01-01

    To investigate the interactions among well-known influencing factors for urinary incontinence (UI), fecal incontinence (FI), and double urinary and fecal incontinence (DI) in the nursing home and hospital setting and to identify profiles of UI, FI, and DI residents and patients. Data from more than 4200 residents and patients from 16 nursing homes and 36 hospitals were collected. This was a cross-sectional study. A cross-sectional study was used for data collection. The Austrian version of the International Prevalence Measurement of Care Problems survey was used to collect data about different nursing care problems (eg, pressure ulcer and incontinence). To improve objectivity, 2 nurses assessed each resident/patient. The Care Dependency Scale (CDS) was used to measure the degree of care dependency regarding different needs such as mobility, with lower scores indicating a higher level of care dependency. A classification and regression tree analysis was used to determine the interactions among factors and develop profiles of incontinent residents and patients. Interactions between the CDS-items of states of Dress/Undress, Hygiene, Mobility, and Eat/Drink and age based on incontinence were found in nursing home residents. In contrast, interactions between the CDS-items Hygiene and Eat/Drink, as well as age and gender based on incontinence, were identified in hospitalized patients. Residents with UI were care dependent with reference to the CDS-item Dress/Undress. Patients with UI were older than 77.5 years and completely, or to a great extent, care dependent with reference to the CDS-item Hygiene. Nursing home residents with DI were completely, or to a great extent, care dependent with regard to the CDS-item Hygiene and completely care dependent with reference to the CDS-item Dress/Undress. In comparison, hospitalized DI patients were completely, or to a great extent, care dependent with regard to the CDS-item Hygiene. The results of this study show that

  9. EPA Urges Home Radon Testing/Protect Your Family from Lung Cancer Caused by Exposure to Radon in Your Home

    EPA Pesticide Factsheets

    WASHINGTON - In recognizing January as National Radon Action Month, EPA encourages Americans around the country to test their homes for this naturally occurring radioactive gas and make 2015 a healthier, safer new year.

  10. Breast cancer genetic risk profile is differentially associated with interval and screen-detected breast cancers.

    PubMed

    Li, J; Holm, J; Bergh, J; Eriksson, M; Darabi, H; Lindström, L S; Törnberg, S; Hall, P; Czene, K

    2015-03-01

    Polygenic risk profiles computed from multiple common susceptibility alleles for breast cancer have been shown to identify women at different levels of breast cancer risk. We evaluated whether this genetic risk stratification can also be applied to discriminate between screen-detected and interval cancers, which are usually associated with clinicopathological and survival differences. A 77 single-nucleotide polymorphism polygenic risk score (PRS) was constructed for breast cancer overall and by estrogen receptor (ER) status. PRS was inspected as a continuous (per standard deviation increment) variable in a case-only design. Modification of the PRS by mammographic density was evaluated by fitting an additional interaction term. PRS weighted by breast cancer overall estimates was found to be differentially associated with 1865 screen-detected and 782 interval cancers in the LIBRO-1 study {age-adjusted odds ratio (OR)perSD [95% confidence interval (CI)] 0.91 [0.83-0.99], P = 0.023}. The association was found to be more significant for PRS weighted by ER-positive breast cancer estimates [ORperSD = 0.90 (0.82-0.98), P = 0.011]. This result was corroborated by two independent studies [combined ORperSD = 0.87 (0.76-1.00), P = 0.058] with no evidence of heterogeneity. When enriched for 'true' interval cancers among nondense breasts, the difference in the association with PRS in screen-detected and interval cancers became more pronounced [ORperSD = 0.74 (0.62-0.89), P = 0.001], with a significant interaction effect between PRS and mammographic density (Pinteraction = 0.017). To our knowledge, this is the first report looking into the genetic differences between screen-detected and interval cancers. It is an affirmation that the two types of breast cancer may have unique underlying biology. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  11. The characteristics of advanced cancer patients followed at home, but admitted to the hospital for the last days of life.

    PubMed

    Mercadante, Sebastiano; Masedu, Francesco; Valenti, Marco; Mercadante, Alessandro; Aielli, Federica

    2016-08-01

    Information regarding advanced cancer patients followed at home who are admitted to the hospital in the last days of life are lacking. The aim of this study was to assess the characteristics of patients who were hospitalized in the last days of life after being assisted by a home palliative care team. The secondary outcome was to identify possible risk factors for hospitalization. The charts were analyzed of a consecutive sample of advanced cancer patients admitted to hospital wards in the last days of life after being followed at home by a palliative care team. Of 550 consecutive patients followed at home, 138 (25.1 %) were admitted to the hospital. Younger patients were more likely to die in the hospital. In a logistic risk analysis adjusted for age, patients with lung and head-neck cancer were more likely to die in the hospital. Patients having a female relative or a female consort as a caregiver were more likely to die at home. CAGE-positive patients (7.25 %), and patients with a shorter period of home assistance were more likely transported to hospital before dying (p = 0.00 and p < 0.024, respectively). The most frequent reason for hospital admission was dyspnea. Admission was more frequent to the oncology ward. Patients who were admitted to the hospital died after a mean of 10.2 days (SD 8.2, range 0-40). This study provides preliminary data on the risk factors of hospitalization at the end of life for advanced cancer patients followed at home.

  12. Population-based home care services in breast cancer: utilization and costs

    PubMed Central

    Mittmann, N.; Isogai, P.K.; Saskin, R.; Liu, N.; Porter, J.M.; Cheung, M.C.; Leighl, N.B.; Hoch, J.S.; Trudeau, M.E.; Evans, W.K.; Dainty, K.N.; Earle, C.C.

    2012-01-01

    Objective To determine utilization and costs of home care services (hcs) for individuals with a diagnosis of breast cancer (bc). Methods Incident cases of invasive bc in women were extracted from the Ontario Cancer Registry (2005–2009) and linked with other Ontario health care administrative databases. Control patients were selected from the population of women never diagnosed with any type of cancer. The types and proportions of hcs used were determined and stratified by disease stage. Attributable home care utilization and costs for bc patients were determined. Factors associated with hcs costs were assessed using regression analysis. Results Among the 39,656 bc and 198,280 control patients identified (median age: 61.6 years for both), 75.4% of bc patients used hcs (62.1% stage i; 85.7% stage ii; 94.6% stage iii; 79.1% stage iv) compared with 14.6% of control patients. The number of hcs used per patient–year were significantly higher for the bc patients than for the control patients (14.97 vs. 6.13, p < 0.01), resulting in higher costs per patient–year ($1,210 vs. $325; $885 attributable cost to bc, p < 0.01). The number of hcs utilized and the associated costs increased as the bc stage increased. In contrast, hcs costs decreased as income increased and as previous health care exposure decreased. Interpretation Patients with bc used twice as many hcs, resulting in costs that were almost 4 times those observed in a matched control group. Less than an additional $1000 per bc patient per year were spent on hcs utilization in the study population. PMID:23300362

  13. Mutation profiles of synchronous colorectal cancers from a patient with Lynch syndrome suggest distinct oncogenic pathways

    PubMed Central

    Shi, Chanjuan; Holt, Jonathan A.; Vnencak-Jones, Cindy L.

    2016-01-01

    Patients with Lynch syndrome often present with multiple synchronous or metachronous colorectal cancers (CRCs). The presence of multiple CRCs with distinct genetic profiles and driver mutations could complicate treatment as each cancer may respond differently to therapy. Studies of sporadic CRCs suggested that synchronous tumors have distinct etiologies, but could not rule out differences in genetic background. The presence of multiple cancers in a patient with a predisposing mutation provides an opportunity to profile synchronous cancers in the same genetic background. Here, we describe the case of a patient with Lynch syndrome that presented with six synchronous CRCs. Microsatellite instability (MSI) and genomic profiling indicated that each lesion had a unique pattern of instability and a distinct profile of affected genes. These findings support the idea that in Lynch syndrome, synchronous CRCs can develop in parallel with distinct mutation profiles and that these differences may inform treatment decisions. PMID:27284491

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

    PubMed

    Cousin, Sophie; Grellety, Thomas; Toulmonde, Maud; Auzanneau, Céline; Khalifa, Emmanuel; Laizet, Yec'han; Tran, Kevin; Le Moulec, Sylvestre; Floquet, Anne; Garbay, Delphine; Robert, Jacques; Hostein, Isabelle; Soubeyran, Isabelle; Italiano, Antoine

    2017-02-08

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

  15. [Physical activity during cancer: Can we define participants' profiles?

    PubMed

    Villaron, Charlène; Marqueste, Tanguy; Eisinger, François; Cappiello, Maria Antonietta; Cury, François

    2017-03-01

    Benefits of physical activity during cancer treatment are widely demonstrated, however, most of patients are not active enough. Several studies have analyzed the different variables that would affect the participation to physical activity programs. The aim of our study was to define profiles of patients who agree to participate in a physical activity program in the medical setting according to the hospital structure in which they receive their care, their past and present habits in sports and their temporal perspectives. Forty-six patients treated from two different hospitals (regional hospital denoted CLCC; and local hospital denoted CH), completed a survey consisting of a questionnaire on their past and present habits in physical activity, ZTPI and a demographic questionnaire. Patients could decide to participate or not in a physical activity program in the medical community. T-tests and Chi(2) were performed to compare the two groups. Chi(2) tests have shown that patients cared in CH are significantly more involved in physical activity program than patients cared in CLCC. Our study points out that the past and present patient PA (physical activity) has no influence on their accession to a physical activity program, however the type of hospital providing patient care could influence their participation. These results should lead us to rethink about the different forms of communication made around the physical activity programs in medical contexts, and about different practical arrangements proposed according to each health facility. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  16. Socio-economic implications of cancer survivorship: results from the PROFILES registry.

    PubMed

    Mols, Floortje; Thong, Melissa S Y; Vissers, Pauline; Nijsten, Tamar; van de Poll-Franse, Lonneke V

    2012-09-01

    The goal of this large population-based study was to examine the socio-economic implications of cancer survivorship. Individuals alive and diagnosed with colorectal cancer and melanoma between 1998 and 2007 or Hodgkin lymphoma, non-Hodgkin lymphoma or multiple myeloma between 1999 and 2008 as registered in the Eindhoven Cancer Registry received a questionnaire on work changes and problems with obtaining a new (or extended) health care insurance, life insurance or a home loan; 70% (n = 2892) responded. Results showed that 28% of all cancer patients experienced changes in their work situation after cancer. Most of them switched to part-time work or stopped working entirely. Patients (3.4%) who tried to obtain a different or upgrade their health care insurance experienced problems and in most cases, these were eventually resolved. Problems with life insurance were somewhat more common with 18% of those who tried to obtain a life insurance experiencing problems. The majority of these patients was rejected by the insurance company (61%) or was accepted at a higher premium (22%). Of the 21% who tried to obtain a home loan, 9% experienced problems. However, 22.2% got accepted eventually, 27.8% got accepted but at a higher mortgage payment and 22.2% got rejected but were eventually accepted by another bank. Almost a third of cancer survivors experienced changes in their work situation after cancer. Problems with obtaining health insurance, life insurance and home loans were also common. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Estimated risk of lung cancer from exposure to radon decay products in U.S. homes: A brief review

    NASA Astrophysics Data System (ADS)

    Nero, Anthony V.

    Recent analyses now permit direct estimation of the risks of lung cancer from radon decay products in U.S. homes. Analysis of data from indoor monitoring in single-family homes yields a tentative frequency distribution of annual-average 222Rn concentrations with an arithmetic mean of 55 Bq m -3 and approximately 2% of homes having 300 Bq m -3 or more. Application of the results of occupational epidemiological studies to indoor exposures, either directly or using recent advances in lung dosimetry, suggests that the average indoor concentration entails a lifetime risk of lung cancer of about 0.4%, contributing about 10% of the total risk of lung cancer. The risk to individuals occupying the homes with 300 Bq m -3 or more for their lifetimes is estimated to exceed 2%, with risks from the homes with thousands of Bq m -3 correspondingly higher, even exceeding the total risk of premature death due to cigarette smoking. Such average and high-level risks greatly exceed ordinarily-considered environmental risks, forcing development of a new perspective on environmental exposures.

  18. Single-cell mutational profiling and clonal phylogeny in cancer

    PubMed Central

    Potter, Nicola E.; Ermini, Luca; Papaemmanuil, Elli; Cazzaniga, Giovanni; Vijayaraghavan, Gowri; Titley, Ian; Ford, Anthony; Campbell, Peter; Kearney, Lyndal; Greaves, Mel

    2013-01-01

    The development of cancer is a dynamic evolutionary process in which intraclonal, genetic diversity provides a substrate for clonal selection and a source of therapeutic escape. The complexity and topography of intraclonal genetic architectures have major implications for biopsy-based prognosis and for targeted therapy. High-depth, next-generation sequencing (NGS) efficiently captures the mutational load of individual tumors or biopsies. But, being a snapshot portrait of total DNA, it disguises the fundamental features of subclonal variegation of genetic lesions and of clonal phylogeny. Single-cell genetic profiling provides a potential resolution to this problem, but methods developed to date all have limitations. We present a novel solution to this challenge using leukemic cells with known mutational spectra as a tractable model. DNA from flow-sorted single cells is screened using multiplex targeted Q-PCR within a microfluidic platform allowing unbiased single-cell selection, high-throughput, and comprehensive analysis for all main varieties of genetic abnormalities: chimeric gene fusions, copy number alterations, and single-nucleotide variants. We show, in this proof-of-principle study, that the method has a low error rate and can provide detailed subclonal genetic architectures and phylogenies. PMID:24056532

  19. Profiling cancer testis antigens in non–small-cell lung cancer

    PubMed Central

    Djureinovic, Dijana; Hallström, Björn M.; Horie, Masafumi; Mattsson, Johanna Sofia Margareta; La Fleur, Linnea; Brunnström, Hans; Madjar, Katrin; Rahnenführer, Jörg; Ekman, Simon; Koyi, Hirsh; Brandén, Eva; Edlund, Karolina; Hengstler, Jan G.; Lambe, Mats; Saito, Akira; Botling, Johan; Uhlén, Mathias

    2016-01-01

    Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non–small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies. PMID:27699219

  20. Profiling cancer testis antigens in non-small-cell lung cancer.

    PubMed

    Djureinovic, Dijana; Hallström, Björn M; Horie, Masafumi; Mattsson, Johanna Sofia Margareta; La Fleur, Linnea; Fagerberg, Linn; Brunnström, Hans; Lindskog, Cecilia; Madjar, Katrin; Rahnenführer, Jörg; Ekman, Simon; Ståhle, Elisabeth; Koyi, Hirsh; Brandén, Eva; Edlund, Karolina; Hengstler, Jan G; Lambe, Mats; Saito, Akira; Botling, Johan; Pontén, Fredrik; Uhlén, Mathias; Micke, Patrick

    2016-07-07

    Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.

  1. Reduced fatalism and increased prevention behavior after two high-profile lung cancer events.

    PubMed

    Portnoy, David B; Leach, Corinne R; Kaufman, Annette R; Moser, Richard P; Alfano, Catherine M

    2014-01-01

    The positive impact of media coverage of high-profile cancer events on cancer prevention behaviors is well-established. However, less work has focused on potential adverse psychological reactions to such events, such as fatalism. Conducting 3 studies, the authors explored how the lung cancer death of Peter Jennings and diagnosis of Dana Reeve in 2005 related to fatalism. Analysis of a national media sample in Study 1 found that media coverage of these events often focused on reiterating the typical profile of those diagnosed with lung cancer; 38% of the media mentioned at least 1 known risk factor for lung cancer, most often smoking. Data from a nationally representative survey in Study 2 found that respondents reported lower lung cancer fatalism, after, compared with before, the events (OR = 0.16, 95% CI [0.03, 0.93]). A sustained increase in call volume to the national tobacco Quitline after these events was found in Study 3. These results suggest that there is a temporal association between high-profile cancer events, the subsequent media coverage, psychological outcomes, and cancer prevention behaviors. These results suggest that high-profile cancer events could be leveraged as an opportunity for large-scale public heath communication campaigns through the dissemination of cancer prevention messages and services.

  2. Experiences of parents with the physical care needs at home of children with cancer: a qualitative study.

    PubMed

    Yildirim Sari, Hatice; Yilmaz, Medine; Ozsoy, Süheyla; Kantar, Mehmet; Cetingul, Nazan

    2013-01-01

    Between cancer treatment courses, children who have not developed any complications or neutropenia are sent home until the start of the next treatment protocol. The aim of this study was to describe the experiences of parents in the home care of children who had been recently diagnosed with cancer and were undergoing cancer treatment but had been discharged from the hospital between treatment protocols. The study was carried out at Ege University, Turkey. Twelve parents of 12 children between 0 and 18 years of age participated in an in-depth interview. The data were analyzed according to Orem's Self-care Deficit Theory. The main themes were basic conditioning factors, self-care agency, and self-care needs. Some parents changed their place of residence because of the cancer treatment, focused on the recovery of the child, and experienced fear, perception difficulties, and difficulties related to self-care needs. Parents report difficulties with extreme emotions and dilemmas in maintaining their daily routines of life secondary to fear of infection and challenges with feeding their children. A well-planned discharge education, home visits, and telephone consultation interventions are essential to meet the needs of children and their parents who are at home between treatment courses.

  3. Support System of Health Professionals as Observed in the Project of Home Care For the Child With Cancer.

    ERIC Educational Resources Information Center

    Gronseth, Evangeline; And Others

    1981-01-01

    Data acquired in personal interviews administered to physicians and nurses who participated in the first year of the Home Care for the Child with Cancer project provided descriptions of individual sources of social support. The results reveal a range of supportive mechanisms and networks within varied institutional contexts. (Author)

  4. Identifying frailty risk profiles of home-dwelling older people: focus on sociodemographic and socioeconomic characteristics.

    PubMed

    Dury, Sarah; De Roeck, Ellen; Duppen, Daan; Fret, Bram; Hoeyberghs, Lieve; Lambotte, Deborah; Van der Elst, Michaël; van der Vorst, Anne; Schols, Jos; Kempen, Gertrudis; Rixt Zijlstra, G A; De Lepeleire, Jan; Schoenmakers, Birgitte; Kardol, Tinie; De Witte, Nico; Verté, Dominique; De Donder, Liesbeth; De Deyn, Peter Paul; Engelborghs, Sebastiaan; Smetcoren, An-Sofie; Dierckx, Eva

    2017-10-01

    This paper investigates risk profiles of frailty among older people, as these are essential for detecting those individuals at risk for adverse outcomes and to undertake specific preventive actions. Frailty is not only a physical problem, but also refers to emotional, social, and environmental hazards. Using data generated from the Belgian Ageing Studies, a cross-sectional study (n = 28,049), we tested a multivariate regression model that included sociodemographic and socioeconomic indicators as well as four dimensions of frailty, for men and women separately. The findings indicated that for both men and women, increased age, having no partner, having moved house in the previous 10 years, having a lower educational level and having a lower household income are risk characteristics for frailty. Moreover, when looking at the different frailty domains, different risk profiles arose, and gender-specific risk characteristics were detected. This paper elaborates on practical implications, and formulates a number of future research recommendations to tackle frailty in an aging society. The conclusion demonstrates the necessity for a thorough knowledge of risk profiles of frailty, as this will save both time and money and permit preventive actions to be more individually tailored.

  5. Chronic radiation enteritis after ovarian cancer: from home parenteral nutrition to oral diet.

    PubMed

    Vidal, Alfonso; de la Cuerda, Cristina; Luis Escat, José; Bretón, Irene; Camblor, Miguel; García-Peris, Pilar

    2006-08-01

    External beam radiation of abdominal and pelvic cavities is a current therapy for gynaecological cancer that often produces radiation-induced bowel injury and malnutrition. A 72-year old patient underwent surgery and external beam radiation therapy for an ovarian carcinoma. Two years later she was found to have intestinal pseudoobstruction related to chronic radiation enteritis and protein-energy malnutrition. Home parenteral nutrition was prescribed due to poor oral intake, but it was discontinued after 6 catheter-related sepsis and upper cava vein thrombosis. Parenteral nutrition could be reintroduced after an angioplasty of that vein, and the patient was operated on with the finding of an incarcerated ileum eventration. Nowadays she maintains a normal nutritional status with oral diet. Radiation enteritis can lead to perforation, fistulae or strictures of the bowel. Malnutrition is common and parenteral nutrition may be necessary. Surgery can solve these complications, achieves good survival rates and can allow stopping parenteral nutrition.

  6. BreCAN-DB: a repository cum browser of personalized DNA breakpoint profiles of cancer genomes

    PubMed Central

    Narang, Pankaj; Dhapola, Parashar; Chowdhury, Shantanu

    2016-01-01

    BreCAN-DB (http://brecandb.igib.res.in) is a repository cum browser of whole genome somatic DNA breakpoint profiles of cancer genomes, mapped at single nucleotide resolution using deep sequencing data. These breakpoints are associated with deletions, insertions, inversions, tandem duplications, translocations and a combination of these structural genomic alterations. The current release of BreCAN-DB features breakpoint profiles from 99 cancer-normal pairs, comprising five cancer types. We identified DNA breakpoints across genomes using high-coverage next-generation sequencing data obtained from TCGA and dbGaP. Further, in these cancer genomes, we methodically identified breakpoint hotspots which were significantly enriched with somatic structural alterations. To visualize the breakpoint profiles, a next-generation genome browser was integrated with BreCAN-DB. Moreover, we also included previously reported breakpoint profiles from 138 cancer-normal pairs, spanning 10 cancer types into the browser. Additionally, BreCAN-DB allows one to identify breakpoint hotspots in user uploaded data set. We have also included a functionality to query overlap of any breakpoint profile with regions of user's interest. Users can download breakpoint profiles from the database or may submit their data to be integrated in BreCAN-DB. We believe that BreCAN-DB will be useful resource for genomics scientific community and is a step towards personalized cancer genomics. PMID:26586806

  7. BreCAN-DB: a repository cum browser of personalized DNA breakpoint profiles of cancer genomes.

    PubMed

    Narang, Pankaj; Dhapola, Parashar; Chowdhury, Shantanu

    2016-01-04

    BreCAN-DB (http://brecandb.igib.res.in) is a repository cum browser of whole genome somatic DNA breakpoint profiles of cancer genomes, mapped at single nucleotide resolution using deep sequencing data. These breakpoints are associated with deletions, insertions, inversions, tandem duplications, translocations and a combination of these structural genomic alterations. The current release of BreCAN-DB features breakpoint profiles from 99 cancer-normal pairs, comprising five cancer types. We identified DNA breakpoints across genomes using high-coverage next-generation sequencing data obtained from TCGA and dbGaP. Further, in these cancer genomes, we methodically identified breakpoint hotspots which were significantly enriched with somatic structural alterations. To visualize the breakpoint profiles, a next-generation genome browser was integrated with BreCAN-DB. Moreover, we also included previously reported breakpoint profiles from 138 cancer-normal pairs, spanning 10 cancer types into the browser. Additionally, BreCAN-DB allows one to identify breakpoint hotspots in user uploaded data set. We have also included a functionality to query overlap of any breakpoint profile with regions of user's interest. Users can download breakpoint profiles from the database or may submit their data to be integrated in BreCAN-DB. We believe that BreCAN-DB will be useful resource for genomics scientific community and is a step towards personalized cancer genomics.

  8. Process Evaluation of a Home-Based Program to Reduce Diet-Related Cancer Risk: The "WIN at Home Series."

    ERIC Educational Resources Information Center

    Finnegan, John R.; And Others

    1992-01-01

    Following media recruitment campaign, WIN at Home, series of diet-related booklets mailed to participants, was evaluated through survey of 226 participants (75 percent). Results showed that 97 percent learned about program through media, women were more likely to learn about it from personal sources, 57 percent shared information with spouses, and…

  9. Process Evaluation of a Home-Based Program to Reduce Diet-Related Cancer Risk: The "WIN at Home Series."

    ERIC Educational Resources Information Center

    Finnegan, John R.; And Others

    1992-01-01

    Following media recruitment campaign, WIN at Home, series of diet-related booklets mailed to participants, was evaluated through survey of 226 participants (75 percent). Results showed that 97 percent learned about program through media, women were more likely to learn about it from personal sources, 57 percent shared information with spouses, and…

  10. Factors Associated with Length of Stay at Home in the Final Month of Life among Advanced Cancer Patients: A Retrospective Chart Review.

    PubMed

    Otsuka, Masatomo

    2017-08-01

    Living at home is an important factor for maintaining high quality of life among patients. Many studies have discussed parameters associated with place of death, but no studies have yet clarified which factors influence the length of stay at home during the end of life. The aim of this study was to identify factors influencing the amount of time spent at home during the final month of life among patients with advanced cancer. A retrospective chart review was conducted for 415 patients with advanced cancer. Multivariate multiple linear regression analysis was used to examine relationships between the length of stay at home during the final month of life and variables measuring patient's background (four indicators), family structure (three indicators) cancer type (four types), chief complaint at initial palliative care referral (seven indicators), and medical interventions (three factors). The multiple linear regression predicting time spent at home in the last month of life yielded partial regression coefficients of 4.2 for past outpatient palliative care services (OPCS) (p < 0.001) and 3.3 for in-home nurse visits (p = 0.003). The most influential factor for length of stay at home in the final month of life was a history of OPCS. Many patients with advanced cancer who receive chemotherapy without OPCS spend time as inpatients after an initial period at home. Palliative care interventions for outpatients effectively enable patients with advanced cancer to adapt and continue living at home.

  11. Cancer treatment at home or in the hospital: what are the costs for French public health insurance? Findings of a comprehensive-cancer centre.

    PubMed

    Raphaël, Remonnay; Yves, Devaux; Giselle, Chvetzoff; Magali, Morelle; Odile, Carrere Marie

    2005-05-01

    The objective of this study was to evaluate the cost of home-cancer-healthcare programs and their potential interest for public health insurance as compared to inpatient cancer care. The study was conducted at the Centre Leon Berard (CLB), a comprehensive cancer centre in Lyon, France. Hospitals at home patients were monitored by nurses and oncologists from the CLB. All patients, who received home treatment over a 15-day period in 2001, were included in the study. Patients were broken down into groups according to the type of healthcare required and the corresponding impact on health insurance expenditure. For each of these patients, a fictive-hospital stay was then reconstructed, which corresponded to the inpatient hospital care that would have been required during the observation period, had hospital at home not been available. The average cost of hospital at home was significantly lower than the corresponding estimated cost for treatment at the hospital (776.6 versus 2012.5, P < 0.001). This difference was particularly high for patients in the "palliative care" group (N = 33) (1201.7 versus 3489.7, P < 0.001), whereas in the "chemotherapy" group, results were not significantly different (N = 34) (225.5 versus 318). Our study suggests that hospitalisation alternatives can generate substantial savings for public health insurance in France.

  12. Flexitouch® Home Maintenance Therapy or Standard Home Maintenance Therapy in Treating Patients With Lower-Extremity Lymphedema Caused by Treatment for Cervical Cancer, Vulvar Cancer, or Endometrial Cancer

    ClinicalTrials.gov

    2014-12-29

    Lymphedema; Stage 0 Cervical Cancer; Stage 0 Uterine Corpus Cancer; Stage 0 Vulvar Cancer; Stage I Uterine Corpus Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Uterine Corpus Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Uterine Corpus Cancer; Stage III Vulvar Cancer; Stage IV Uterine Corpus Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Stage IVB Vulvar Cancer

  13. Pathway analysis of kidney cancer using proteomics and metabolic profiling

    PubMed Central

    Perroud, Bertrand; Lee, Jinoo; Valkova, Nelly; Dhirapong, Amy; Lin, Pei-Yin; Fiehn, Oliver; Kültz, Dietmar; Weiss, Robert H

    2006-01-01

    Background Renal cell carcinoma (RCC) is the sixth leading cause of cancer death and is responsible for 11,000 deaths per year in the US. Approximately one-third of patients present with disease which is already metastatic and for which there is currently no adequate treatment, and no biofluid screening tests exist for RCC. In this study, we have undertaken a comprehensive proteomic analysis and subsequently a pathway and network approach to identify biological processes involved in clear cell RCC (ccRCC). We have used these data to investigate urinary markers of RCC which could be applied to high-risk patients, or to those being followed for recurrence, for early diagnosis and treatment, thereby substantially reducing mortality of this disease. Results Using 2-dimensional electrophoresis and mass spectrometric analysis, we identified 31 proteins which were differentially expressed with a high degree of significance in ccRCC as compared to adjacent non-malignant tissue, and we confirmed some of these by immunoblotting, immunohistochemistry, and comparison to published transcriptomic data. When evaluated by several pathway and biological process analysis programs, these proteins are demonstrated to be involved with a high degree of confidence (p values < 2.0 E-05) in glycolysis, propanoate metabolism, pyruvate metabolism, urea cycle and arginine/proline metabolism, as well as in the non-metabolic p53 and FAS pathways. In a pilot study using random urine samples from both ccRCC and control patients, we performed metabolic profiling and found that only sorbitol, a component of an alternative glycolysis pathway, is significantly elevated at 5.4-fold in RCC patients as compared to controls. Conclusion Extensive pathway and network analysis allowed for the discovery of highly significant pathways from a set of clear cell RCC samples. Knowledge of activation of these processes will lead to novel assays identifying their proteomic and/or metabolomic signatures in biofluids

  14. Human breast cancer associated fibroblasts exhibit subtype specific gene expression profiles

    PubMed Central

    2012-01-01

    Background Breast cancer is a heterogeneous disease for which prognosis and treatment strategies are largely governed by the receptor status (estrogen, progesterone and Her2) of the tumor cells. Gene expression profiling of whole breast tumors further stratifies breast cancer into several molecular subtypes which also co-segregate with the receptor status of the tumor cells. We postulated that cancer associated fibroblasts (CAFs) within the tumor stroma may exhibit subtype specific gene expression profiles and thus contribute to the biology of the disease in a subtype specific manner. Several studies have reported gene expression profile differences between CAFs and normal breast fibroblasts but in none of these studies were the results stratified based on tumor subtypes. Methods To address whether gene expression in breast cancer associated fibroblasts varies between breast cancer subtypes, we compared the gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main subtypes; seven ER+, seven triple negative (TNBC) and six Her2+. Results We observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER + cancers, particularly in pathways associated with cytoskeleton and integrin signaling. In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs likely contribute to the enhanced migration of breast cancer cells in transwell assays and may contribute to the unfavorable prognosis of Her2+ breast cancer. Conclusions These data demonstrate that in addition to the distinct molecular profiles that characterize the neoplastic cells, CAF gene expression is also differentially regulated in distinct subtypes of breast cancer. PMID:22954256

  15. Profiling of cytokines in human epithelial ovarian cancer ascites

    PubMed Central

    Matte, Isabelle; Lane, Denis; Laplante, Claude; Rancourt, Claudine; Piché, Alain

    2012-01-01

    Background The behavior of tumor cells is influenced by the composition of the surrounding tumor environment. The importance of ascites in ovarian cancer (OC) progression is being increasingly recognized. The characterization of soluble factors in ascites is essential to understand how this environment affects OC progression. The development of cytokine arrays now allows simultaneous measurement of multiple cytokines per ascites using a single array. Methods We applied a multiplex cytokine array technology that simultaneously measures the level of 120 cytokines in ascites from 10 OC patients. The ascites concentration of a subset (n = 5) of cytokines that was elevated based on the multiplex array was validated by commercially available ELISA. The ascites level of these 5 cytokines was further evaluated by ELISA in a cohort of 38 patients. Kaplan-Meier analysis was used to assess the association of cytokine expression with progression-free survival (PFS) in this cohort. Results We observed a wide variability of expression between different cytokines and levels of specific cytokines also varied in the 10 malignant ascites tested. Fifty-three (44%) cytokines were not detected in any of the 10 ascites. The level of several factors including, among others, angiogenin, angiopoietin-2, GRO, ICAM-1, IL-6, IL-6R, IL-8, IL-10, leptin, MCP-1, MIF NAP-2, osteprotegerin (OPG), RANTES, TIMP-2 and UPAR were elevated in most malignant ascites. Higher levels of OPG, IL-10 and leptin in OC ascites were associated with shorter PFS. IL-10 was shown to promote the anti-apoptotic activity of malignant ascites whereas OPG did not. Conclusion Our data demonstrated that there is a complex network of cytokine expression in OC ascites. Characterization of cytokine profiles in malignant ascites may provide information from which to prioritize key functional cytokines and understand the mechanism by which they alter tumor cells behavior. A better understanding of the cytokine network is

  16. Pre-exposure of human adipose mesenchymal stem cells to soluble factors enhances their homing to brain cancer.

    PubMed

    Smith, Chris L; Chaichana, Kaisorn L; Lee, Young M; Lin, Benjamin; Stanko, Kevin M; O'Donnell, Thomas; Gupta, Saksham; Shah, Sagar R; Wang, Joanne; Wijesekera, Olindi; Delannoy, Michael; Levchenko, Andre; Quiñones-Hinojosa, Alfredo

    2015-03-01

    Recent research advances have established mesenchymal stem cells (MSCs) as a promising vehicle for therapeutic delivery. Their intrinsic tropism for brain injury and brain tumors, their lack of immunogenicity, and their ability to breach the blood-brain barrier make these cells an attractive potential treatment of brain disorders, including brain cancer. Despite these advantages, the efficiency of MSC homing to the brain has been limited in commonly used protocols, hindering the feasibility of such therapies. In the present study, we report a reproducible, comprehensive, cell culture-based approach to enhance human adipose-derived MSC (hAMSC) engraftment to brain tumors. We used micro- and nanotechnological tools to systematically model several steps in the putative homing process. By pre-exposing hAMSCs to glioma-conditioned media and the extracellular matrix proteins fibronectin and laminin, we achieved significant enhancements of the individual homing steps in vitro. This homing was confirmed in an in vivo rodent model of brain cancer. This comprehensive, cell-conditioning approach provides a novel method to enhance stem cell homing to gliomas and, potentially, other neurological disorders. ©AlphaMed Press.

  17. Amino Acid Profiling of Zinc Resistant Prostate Cancer Cell Lines: Associations With Cancer Progression.

    PubMed

    Kratochvilova, Monika; Raudenska, Martina; Heger, Zbynek; Richtera, Lukas; Cernei, Natalia; Adam, Vojtech; Babula, Petr; Novakova, Marie; Masarik, Michal; Gumulec, Jaromir

    2017-05-01

    Failure in intracellular zinc accumulation is a key process in prostate carcinogenesis. Nevertheless, epidemiological studies of zinc administration have provided contradicting results. In order to examine the impact of the artificial intracellular increase of zinc(II) ions on prostate cancer metabolism, PNT1A, 22Rv1, and PC-3 prostatic cell lines-depicting different stages of cancer progression-and their zinc-resistant counterparts were used. To determine "benign" and "malignant" metabolic profiles, amino acid patterns, gene expression, and antioxidant capacity of these cell lines were assessed. Amino acid profiles were examined using an ion-exchange liquid chromatography. Intracellular zinc content was measured by atomic absorption spectrometry. Metallothionein was quantified using differential pulse voltammetry. The content of reduced glutathione was determined using high performance liquid chromatography coupled with an electrochemical detector. Cellular antioxidant capacity was determined by the ABTS test and gene expression analysis was performed by qRT-PCR. Long-term zinc treatment was shown to reroute cell metabolism from benign to more malignant type. Long-term application of high concentration of zinc(II) significantly enhanced cisplatin resistance, invasiveness, cellular antioxidant capacity, synthesis of glutathione, and expression of treatment resistance- and stemness-associated genes (SOX2, POU5F1, BIRC5). Tumorous cell lines universally displayed high accumulation of aspartate and sarcosine and depletion of essential amino acids. Increased aspartate/threonine, aspartate/methionine, and sarcosine/serine ratios were associated with cancer phenotype with high levels of sensitivity and specificity. Prostate 77: 604-616, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Profile in community cooperation: Delaware big in fighting cancer.

    PubMed

    Botvin, Judith D

    2005-01-01

    The Delaware Cancer Treatment Program, created under an official state mandate, provides support for Delawareans diagnosed with any cancer who are without health insurance and who are ineligible for Medicaid.The multi-faceted campaign shown here includes information kits designed to help community leaders as they encourage men to be screened for prostate cancer. Also, it directly enlists physicians in this effort.

  19. Tissue metabolic profiling of human gastric cancer assessed by (1)H NMR.

    PubMed

    Wang, Huijuan; Zhang, Hailong; Deng, Pengchi; Liu, Chunqi; Li, Dandan; Jie, Hui; Zhang, Hu; Zhou, Zongguang; Zhao, Ying-Lan

    2016-06-29

    Gastric cancer is the fourth most common cancer and the second most deadly cancer worldwide. Study on molecular mechanisms of carcinogenesis will play a significant role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to identify the potential biomarkers for the early diagnosis of gastric cancer. In this study, we reported the metabolic profiling of tissue samples on a large cohort of human gastric cancer subjects (n = 125) and normal controls (n = 54) based on (1)H nuclear magnetic resonance ((1)H NMR) together with multivariate statistical analyses (PCA, PLS-DA, OPLS-DA and ROC curve). The OPLS-DA model showed adequate discrimination between cancer tissues and normal controls, and meanwhile, the model excellently discriminated the stage-related of tissue samples (stage I, 30; stage II, 46; stage III, 37; stage IV, 12) and normal controls. A total of 48 endogenous distinguishing metabolites (VIP > 1 and p < 0.05) were identified, 13 of which were changed with the progression of gastric cancer. These modified metabolites revealed disturbance of glycolysis, glutaminolysis, TCA, amino acids and choline metabolism, which were correlated with the occurrence and development of human gastric cancer. The receiver operating characteristic diagnostic AUC of OPLS-DA model between cancer tissues and normal controls was 0.945. And the ROC curves among different stages cancer subjects and normal controls were gradually improved, the corresponding AUC values were 0.952, 0.994, 0.998 and 0.999, demonstrating the robust diagnostic power of this metabolic profiling approach. As far as we know, the present study firstly identified the differential metabolites in various stages of gastric cancer tissues. And the AUC values were relatively high. So these results suggest that the metabolic profiling of gastric cancer tissues has great potential in detecting this

  20. Differences in gene expression profiles and carcinogenesis pathways between colon and rectal cancer.

    PubMed

    Li, Jing Nan; Zhao, Li; Wu, Jun; Wu, Bin; Yang, Hong; Zhang, Heng Hui; Qian, Jia Ming

    2012-01-01

    Colon cancer is more common in the USA and Europe than that in China, for reasons that are unclear. The aim of this study was to investigate the differences in gene expression profiles and carcinogenesis pathways between colon and rectal cancer. Expression profiling of primary tumor tissues from 12 colon and 12 rectal cancers was performed using oligonucleotide microarray analysis. All samples were strictly matched by clinical features. Bioinformatic analyses such as the Kyoto Encyclopedia of Genes and Genomes were used to identify genes and pathways specifically associated with colon or rectal cancers. A total of 824 genes were differentially expressed in colon and rectal cancers. All differential gene interactions in the Signal-Net were analyzed. More genes were differentially expressed and included in the Signal-Net for rectal than colon cancer. Of the genes differentially expressed between colon and rectal cancer, S100P, the Reg family, ACTN1, CAMK2G and ACAT1 were the most significantly altered. Genes involved in the cell cycle pathway were present in rectal and colon cancers, but were more important in rectal cancer. The p53 and metabolic signaling pathways were significantly different in colon and rectal cancers. Gene expression profiles differed between colon and rectal cancer, with metabolic pathways being more important in rectal cancer. The oncogenesis of rectal cancer may be more complex than that of colon cancer. Some genes could be new biomarkers for distinguishing between these two cancers. © 2011 The Authors. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

  1. [A study of 31 terminally ill cancer patients who received pure oxycodone injections at home].

    PubMed

    Sasaki, Tsubasa; Kawagoe, Izumi

    2014-11-01

    Since the launch of pure oxycodone injections in May 2012, it has been possible to use oxycodone without opioid rotation. Although an extremely important step showing progress, very few studies regarding the use of pure oxycodone injections have been performed. In this study, we evaluated the safety and efficacy of pure oxycodone injections in 31 terminally ill cancer patients receiving home care. The difficulty in oral oxycodone intake was the main reason for changing to pure oxycodone injections. The mean administered period of subcutaneous pure oxycodone was 5.6 ± 6.7 days. One out of 5 patients receiving pure oxycodone injections complained of worsening sleepiness. However, other symptoms improved. In addition, in cases wherein pure oxycodone injection was the initiating opioid, 1 out of 6 patients showed no improvement of respiratory discomfort, while other symptoms improved. It was difficult to evaluate more patients because of the short period for administration. Although 5 patients experienced skin problems, they were successfully managed by changing the injection site. Of these 5 patients, 2 patients had sensitive skin, with a previous history of alcohol rash. In conclusion, our study suggests that pure oxycodone injections are beneficial over oral oxycodone treatment for terminally ill cancer patients. However, further evaluation of skin problems associated with pure oxycodone injections is required by performing larger studies.

  2. Nocturnal sleep-wake parameters of adolescents at home following cancer chemotherapy.

    PubMed

    Walker, Amy J; Johnson, Kyle P; Miaskowski, Christine; Gedaly-Duff, Vivian

    2012-07-01

    The purpose of this descriptive, longitudinal study was to describe objective nocturnal sleep-wake parameters of adolescents at home after receiving chemotherapy in the hospital or outpatient clinic and explore differences in sleep variables by age, gender, and corticosteroid use. We collected 7 days of wrist actigraphy and sleep diary data from 48 adolescents (10-19 years) who were receiving cancer chemotherapy for a primary or secondary cancer or a relapse. The actigraphic sleep variables included rest interval (i.e., time in bed), sleep onset, sleep offset, sleep duration, total sleep time (TST), wake after sleep onset (WASO), and %WASO. Of the 48 adolescents, 38 had at least five nights of scored actigraphy and were included in analyses. Older (13-18 years) adolescents went to bed later and had fewer minutes of TST than younger adolescents (10-12 years). Exploratory analyses revealed no differences between adolescents who were taking oral corticosteroids (i.e., prednisone, dexamethasone) and those who were not or between males and females. These adolescents had sleep durations that met or exceeded the recommended sleep duration for their age groups but experienced significant WASO. Further research is needed to estimate sleep needs of adolescents during chemotherapy and determine factors that contribute to nocturnal wake-time so that targeted interventions can be designed to improve sleep quality.

  3. Targeting cancer cells via tumor-homing peptide CREKA functional PEG nanoparticles.

    PubMed

    Okur, Aysu Ceren; Erkoc, Pelin; Kizilel, Seda

    2016-11-01

    Targeting cell microenvironment via nano-particle based therapies holds great promise for the treatment of various diseases. One of the main challenges in targeted delivery of nanoparticles for cancer therapy is the reduced localization of delivery vehicles to the tumor site. The therapeutic efficacy of drugs can be improved by recruiting delivery vehicles towards specific region of tumorigenesis in the body. Here, we demonstrate an effective approach in creating PEG particles via water-in-water emulsion technique with a tumor-homing peptide CREKA functionalization. The CREKA conjugated hydrogel nanoparticles were found to be more effective at inducing Doxorubicin (DOX)-mediated apoptosis compared to that of particles conjugated with laminin peptide IKVAV. Fluorescence intensity analysis on confocal micrographs suggested significantly higher cellular uptake of CREKA conjugated PEG particles than internalization of nanoparticles in other groups. We observed that fibrin binding ability of PEG particles could be increased up to 94% through CREKA conjugation. Our results suggest the possibility of cancer cell targeting via CREKA-functional PEG nanoparticles.

  4. Profiles of and practices in crisis resolution and home treatment teams in Norway: a longitudinal survey study

    PubMed Central

    2011-01-01

    Background Crisis resolution and home treatment (CRHT) is one of the more recent modes of delivering acute mental health care in the community. The objective of the study was to describe the standardizations and variations in the CRHT teams in Norway in order to gain knowledge regarding the structures and processes of CRHT teams. Methods A longitudinal survey of five CRHT teams in Norway was carried out for a period of 18 months with two sets of questionnaires-one for CRHT team profiles for a bi-yearly survey and the other for services and practices of CRHT teams for a monthly survey. Results The five CRHT teams were configured by a set of common basic characteristics in their operations, while at the same time were variant in several areas of the teams' structures and processes. Significant differences among the teams were evident in terms of the structural aspects such as service locality, staffing and team make-up, caseload, service hours, and travel time, and the process aspects such as the number of referrals received, referral source, admission, service duration, and discharge destination. These variations are reflected upon the perspectives regarding the nature of mental health crisis, the conflicting policies in mental health services, and the nature of home-based mental health care. Conclusions The diversity in the way CRHT teams are established and operate needs to be examined further in order to understand the reasons for such variations and their impact on the quality of services to service users and in relation to the total mental health service system in a community. PMID:21878115

  5. [Home parenteral nutrition in patients with advanced cancer: experience of a single centre over ten years].

    PubMed

    Moreno Villares, J M; Gomis Muñoz, P; Valero Zanuy, Ma A; León Sanz, M

    2004-01-01

    The use of Home Parenteral Nutrition (HPN) in patients with advanced cancer without the possibility of curative treatment continues to be a controversial subject entailing a considerable emotional burden. Nonetheless, this group of patients constitutes the main indication for HPN in many programmes. To present the characteristics of a series of patients included on an HPN programme over the last ten years. Retrospective study of the case histories of the 11 patients who received HPN over this period. The demographic and clinical details were noted along with their complications and evolution for comparison with those of a control group of patients with benign disease receiving HPN over the same period. For the comparisons, Student's t test and the chi-squared test were used as and when indicated. Results were considered statistically significant if p < 0.05. Eleven patients received HPN, nine of them because of an irresoluble intestinal obstruction and two because of a high flow fistula. The mean age at the start of HPN was 50.8 +/- 12.7 years versus 37.3 +/- 17.2 years for the group with benign disease (p < 0.05). The mean duration of HPN was 71.05 +/- 217 days in the first group, notably less than the second (387.15 +/- 995.85; p < 0.05), with a range between 5 and 760 days. The patients received the infusion through a previously implanted subcutaneous reservoir (n = 9) and on two occasions, electively, through a tunnelled catheter. The infection rate was higher in the group with cancer (0.34 episodes per patient and 1,000 days on HPN) than in the group with benign disease (0.08 episodes; p < 0.05). HPN was suspended in only one of the patients more than 5 days prior to death due to clinical deterioration. Two patients required admission due to a complication associated with the technique. In both cases, a fungal infection of the blood made it necessary to withdraw the catheter. The quality of life, measured by means of an activity scale, was similar at the start

  6. Current clinical application of genomic and proteomic profiling in non-small-cell lung cancer.

    PubMed

    Tanvetyanon, Tawee; Creelan, Benjamin C; Chiappori, Alberto A

    2014-01-01

    Genomic or proteomic profiling of cancer can be broadly defined as a systematic grouping of cancer based on its genetic or protein makeup. In the management of non-small-cell lung cancer (NSCLC), genomic and proteomic profiling applications have become useful in early disease detection, diagnosis, treatment, and prognostication. We reviewed the recent literature on the applications of genomic and proteomic profiling in NSCLC. Important applications were summarized into those already adopted as standard care and those still under investigation. For genomic profiling, testing for EGFR mutation and ALK rearrangement has become routine for adenocarcinoma. Multiplex assay and malignancy-risk gene signature are both important applications in development. A test to predict outcome after treatment with an epidermal growth factor rector/tyrosine kinase inhibitor and a screening blood test for lung cancer are being investigated for use in proteomic profiling. Genomic profiling is routine in patients with NSCLC, and proteomic profiling shows promise. Additional genomic and proteomic profiling applications may also prove to be useful contributions in the care of these patients.

  7. Acute impact of home parenteral nutrition in patients with late-stage cancer on family caregivers: preliminary data.

    PubMed

    Santarpia, Lidia; Bozzetti, Federico

    2017-09-18

    Since there is no information regarding quality of life of caregivers assisting patients with advanced malignancy on home parenteral nutrition, herewith we report a preliminary series of 19 patients who received total parenteral nutrition at home under the strict supervision of their relatives. The relatives of 19 incurable patients with cancer-related cachexia, discharged from the hospital with a home parenteral nutrition program, were prospectively studied. They filled out a validated questionnaire, the Family Strain Questionnaire Short Form, prior to patient discharge and after 2 weeks of home care. The questionnaire included 30 items, which explored different domains regarding the superimposed burden on caregivers in relation to the assistance given to their relatives. Our findings show that the basal level of strain was relatively high (about three quarters of positive answers) but did not increase after 2 weeks of home care. Similarly, there was no difference in the nutritional status and quality of life of the patients. Eight patients and their relatives could be also analyzed after 2 months and the results maintained unchanged. This preliminary investigation shows that home parenteral nutrition does not exacerbate the level of strain on caregivers involved in surveillance of such a supportive intervention. It is possible that the perception of an active contribution to the benefit of patients, who maintained unchanged their nutritional status and quality of life, could gratify caregivers despite the objective burden in the constant supervision of administering Parenteral Nutrition.

  8. A qualitative exploration of district nurses' care of patients with advanced cancer: the challenges of supporting families within the home.

    PubMed

    Wilson, Charlotte; Griffiths, Jane; Ewing, Gail; Connolly, Michael; Grande, Gunn

    2014-01-01

    In the United Kingdom, district nurses (DNs) support patients with advanced cancer in their homes. Although evidence suggests that DNs emphasize the distinctiveness of home rather than hospital settings, little is known about the specific challenges of delivering care in family-home settings. The objective of this study was to explore DNs' experiences of supporting patients within families. Focus groups were conducted with 40 DNs from 4 areas in the United Kingdom. The groups were digitally recorded and facilitated by researchers using a flexible topic guide. Verbatim transcripts were analyzed using thematic content analysis. Case-load complexity (household volatility) and family dynamics posed distinct challenges for nurses supporting patients. Many family members struggled with accepting the patients' prognosis and were complicit in withholding information. At times, this foreclosed a consideration of palliative options. Carers provide a great deal of positive supportive care within the home. However, for some, the home is characterized by conflict rather than consensus. Complexities surrounding family relationships pose a distinctive and challenging environment for DNs. Education and training of DNs should be designed to address the challenges of supporting patients within the family-home setting.

  9. Molecular Profiling of Breast Cancer Cell Lines Defines Relevant Tumor Models and Provides a Resource for Cancer Gene Discovery

    PubMed Central

    Bocanegra, Melanie; Choi, Yoon-La; Girard, Luc; Gandhi, Jeet; Kwei, Kevin A.; Hernandez-Boussard, Tina; Wang, Pei; Gazdar, Adi F.; Minna, John D.; Pollack, Jonathan R.

    2009-01-01

    Background Breast cancer cell lines have been used widely to investigate breast cancer pathobiology and new therapies. Breast cancer is a molecularly heterogeneous disease, and it is important to understand how well and which cell lines best model that diversity. In particular, microarray studies have identified molecular subtypes–luminal A, luminal B, ERBB2-associated, basal-like and normal-like–with characteristic gene-expression patterns and underlying DNA copy number alterations (CNAs). Here, we studied a collection of breast cancer cell lines to catalog molecular profiles and to assess their relation to breast cancer subtypes. Methods Whole-genome DNA microarrays were used to profile gene expression and CNAs in a collection of 52 widely-used breast cancer cell lines, and comparisons were made to existing profiles of primary breast tumors. Hierarchical clustering was used to identify gene-expression subtypes, and Gene Set Enrichment Analysis (GSEA) to discover biological features of those subtypes. Genomic and transcriptional profiles were integrated to discover within high-amplitude CNAs candidate cancer genes with coordinately altered gene copy number and expression. Findings Transcriptional profiling of breast cancer cell lines identified one luminal and two basal-like (A and B) subtypes. Luminal lines displayed an estrogen receptor (ER) signature and resembled luminal-A/B tumors, basal-A lines were associated with ETS-pathway and BRCA1 signatures and resembled basal-like tumors, and basal-B lines displayed mesenchymal and stem/progenitor-cell characteristics. Compared to tumors, cell lines exhibited similar patterns of CNA, but an overall higher complexity of CNA (genetically simple luminal-A tumors were not represented), and only partial conservation of subtype-specific CNAs. We identified 80 high-level DNA amplifications and 13 multi-copy deletions, and the resident genes with concomitantly altered gene-expression, highlighting known and novel

  10. Gene expression profiles of prostate cancer stem cells isolated by aldehyde dehydrogenase activity assay.

    PubMed

    Nishida, Sachiyo; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Kitamura, Hiroshi; Takahashi, Akari; Masumori, Naoya; Tsukamoto, Taiji; Sato, Noriyuki

    2012-07-01

    Prostate cancer cells include a small population of cancer stem-like/cancer initiating cells, which have roles in cancer initiation and progression. Recently aldehyde dehydrogenase activity was used to isolate stem cells of various cancer and normal cells. We evaluated the aldehyde dehydrogenase activity of the human prostate cancer cell line 22Rv1 (ATCC®) with the ALDEFLUOR® assay and determined its potency as prostate cancer stem-like/cancer initiating cells. The human prostate cancer cell line 22Rv1 was labeled with ALDEFLUOR reagent and analyzed by flow cytometry. ALDH1(high) and ALDH1(low) cells were isolated and tumorigenicity was evaluated by xenograft transplantation into NOD/SCID mice. Tumor sphere forming ability was evaluated by culturing in a floating condition. Invasion capability was evaluated by the Matrigel™ invasion assay. Gene expression profiling was assessed by microarrays and reverse transcriptase-polymerase chain reaction. ALDH1(high) cells were detected in 6.8% of 22Rv1 cells, which showed significantly higher tumorigenicity than ALDH1(low) cells in NOD/SCID mice (p < 0.05). Gene expression profiling revealed higher expression of the stem cell related genes PROM1 and NKX3-1 in ALDH1(high) cells than in ALDH1(low) cells. ALDH1(high) cells also showed higher invasive capability and sphere forming capability than ALDH1(low) cells. Results indicate that cancer stem-like/cancer initiating cells are enriched in the ALDH1(high) population of the prostate cancer cell line 22Rv1. This approach may provide a breakthrough to further clarify prostate cancer stem-like/cancer initiating cells. To our knowledge this is the first report of cancer stem-like/cancer initiating cells of 22Rv1 using the aldehyde dehydrogenase activity assay. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  11. Institutional implementation of clinical tumor profiling on an unselected cancer population

    PubMed Central

    Sholl, Lynette M.; Do, Khanh; Shivdasani, Priyanka; Cerami, Ethan; Dubuc, Adrian M.; Kuo, Frank C.; Garcia, Elizabeth P.; Jia, Yonghui; Davineni, Phani; Abo, Ryan P.; van Hummelen, Paul; Thorner, Aaron R.; Ducar, Matthew; Berger, Alice H.; Nishino, Mizuki; Janeway, Katherine A.; Church, Alanna; Harris, Marian; Rojas-Rudilla, Vanesa; Ligon, Azra H.; Ramkissoon, Shakti; Cleary, James M.; Matulonis, Ursula; Oxnard, Geoffrey R.; Chao, Richard; Tassell, Vanessa; Christensen, James; Hahn, William C.; Kantoff, Philip W.; Kwiatkowski, David J.; Johnson, Bruce E.; Meyerson, Matthew; Garraway, Levi A.; Shapiro, Geoffrey I.; Rollins, Barrett J.; Lindeman, Neal I.; MacConaill, Laura E.

    2016-01-01

    BACKGROUND. Comprehensive genomic profiling of a patient’s cancer can be used to diagnose, monitor, and recommend treatment. Clinical implementation of tumor profiling in an enterprise-wide, unselected cancer patient population has yet to be reported. METHODS. We deployed a hybrid-capture and massively parallel sequencing assay (OncoPanel) for all adult and pediatric patients at our combined cancer centers. Results were categorized by pathologists based on actionability. We report the results for the first 3,727 patients tested. RESULTS. Our cohort consists of cancer patients unrestricted by disease site or stage. Across all consented patients, half had sufficient and available (>20% tumor) material for profiling; once specimens were received in the laboratory for pathology review, 73% were scored as adequate for genomic testing. When sufficient DNA was obtained, OncoPanel yielded a result in 96% of cases. 73% of patients harbored an actionable or informative alteration; only 19% of these represented a current standard of care for therapeutic stratification. The findings recapitulate those of previous studies of common cancers but also identify alterations, including in AXL and EGFR, associated with response to targeted therapies. In rare cancers, potentially actionable alterations suggest the utility of a “cancer-agnostic” approach in genomic profiling. Retrospective analyses uncovered contextual genomic features that may inform therapeutic response and examples where diagnoses revised by genomic profiling markedly changed clinical management. CONCLUSIONS. Broad sequencing-based testing deployed across an unselected cancer cohort is feasible. Genomic results may alter management in diverse scenarios; however, additional barriers must be overcome to enable precision cancer medicine on a large scale. FUNDING. This work was supported by DFCI, BWH, and the National Cancer Institute (5R33CA155554 and 5K23CA157631). PMID:27882345

  12. Institutional implementation of clinical tumor profiling on an unselected cancer population.

    PubMed

    Sholl, Lynette M; Do, Khanh; Shivdasani, Priyanka; Cerami, Ethan; Dubuc, Adrian M; Kuo, Frank C; Garcia, Elizabeth P; Jia, Yonghui; Davineni, Phani; Abo, Ryan P; Pugh, Trevor J; van Hummelen, Paul; Thorner, Aaron R; Ducar, Matthew; Berger, Alice H; Nishino, Mizuki; Janeway, Katherine A; Church, Alanna; Harris, Marian; Ritterhouse, Lauren L; Campbell, Joshua D; Rojas-Rudilla, Vanesa; Ligon, Azra H; Ramkissoon, Shakti; Cleary, James M; Matulonis, Ursula; Oxnard, Geoffrey R; Chao, Richard; Tassell, Vanessa; Christensen, James; Hahn, William C; Kantoff, Philip W; Kwiatkowski, David J; Johnson, Bruce E; Meyerson, Matthew; Garraway, Levi A; Shapiro, Geoffrey I; Rollins, Barrett J; Lindeman, Neal I; MacConaill, Laura E

    2016-11-17

    BACKGROUND. Comprehensive genomic profiling of a patient's cancer can be used to diagnose, monitor, and recommend treatment. Clinical implementation of tumor profiling in an enterprise-wide, unselected cancer patient population has yet to be reported. METHODS. We deployed a hybrid-capture and massively parallel sequencing assay (OncoPanel) for all adult and pediatric patients at our combined cancer centers. Results were categorized by pathologists based on actionability. We report the results for the first 3,727 patients tested. RESULTS. Our cohort consists of cancer patients unrestricted by disease site or stage. Across all consented patients, half had sufficient and available (>20% tumor) material for profiling; once specimens were received in the laboratory for pathology review, 73% were scored as adequate for genomic testing. When sufficient DNA was obtained, OncoPanel yielded a result in 96% of cases. 73% of patients harbored an actionable or informative alteration; only 19% of these represented a current standard of care for therapeutic stratification. The findings recapitulate those of previous studies of common cancers but also identify alterations, including in AXL and EGFR, associated with response to targeted therapies. In rare cancers, potentially actionable alterations suggest the utility of a "cancer-agnostic" approach in genomic profiling. Retrospective analyses uncovered contextual genomic features that may inform therapeutic response and examples where diagnoses revised by genomic profiling markedly changed clinical management. CONCLUSIONS. Broad sequencing-based testing deployed across an unselected cancer cohort is feasible. Genomic results may alter management in diverse scenarios; however, additional barriers must be overcome to enable precision cancer medicine on a large scale. FUNDING. This work was supported by DFCI, BWH, and the National Cancer Institute (5R33CA155554 and 5K23CA157631).

  13. [Trial of home anti-cancer chemotherapy with infusion of 5-FU and low-dose cisplatin].

    PubMed

    Muto, A; Ashino, Y; Ito, H; Kanno, A; Moriyama, A; Hiraga, M

    1996-12-01

    We tried home anti-cancer chemotherapy for patients with advanced or recurrent cancer of the digestive system, using two disposable balloon pumps connected to an implantable drug delivery system via central venous line. There were 33 patients under 75 years old, including 20 cases of gastric cancer, 9 cases of colorectal cancer, 2 cases of cholangiocarcinoma and 2 cases of esophageal cancer enrolled in this study. The protocol was combined chemotherapy with continuous intravenous infusion of 5-FU (300 mg/body/day) and low-dose intravenous injection of cisplatin (5 mg/body/day) in 10-day courses for two weeks, and it was repeated 3 times for 6 weeks. Because of side effects such as nausea, vomiting and bone marrow suppression, treatment was discontinued in 12 cases with peritoneal cancer infiltration. In two of 10 with estimable disease, the reduction of the metastatic lymph node was observed, but no effect was shown in the colorectal metastatic liver tumor. Thanks to the portability of the pump with this method, the patient need not undergo hospitalization. Moreover, there is no renal dysfunction or other major side effects, quality of life is not compromised and a return to family and social life is possible. Thus, if the patient cannot take the oral nutrition, it is easy to start home hyper-alimentation.

  14. Ejaculation profiles of men following radiation therapy for prostate cancer.

    PubMed

    Sullivan, John F; Stember, Doron S; Deveci, Serkan; Akin-Olugbade, Yemi; Mulhall, John P

    2013-05-01

    Radical prostatectomy (RP) is associated with anejaculation, which for some men is a source of bother and sexual dissatisfaction. Clinical experience has shown us some men after pelvic radiation therapy (RT) also experience anejaculation. This analysis was conducted to define the ejaculation profiles of men after RT for prostate cancer (PCa). As a routine part of the sexual health evaluation for post-RT patients, men provided information regarding their ejaculatory function and orgasm. Analysis was conducted of a sexual medicine database reviewing demographic data, PCa factors, erectile, ejaculatory, and orgasmic function. Men with prior history of RP, cryotherapy, focal therapies, and androgen deprivation therapy (ADT) were excluded. Patients completed the International Index of Erectile Function (IIEF) questionnaire at follow-up visits commencing with the first posttreatment visit and specific attention was paid to the IIEF orgasm domain. Three hundred and sixty-four consecutive patients were included. Two hundred and fifty-two patients had external beam, and 112 patients had brachytherapy (BT). Mean age was 64 ± 11 (42-78) years and mean follow-up after RT was 6 ± 4.5 years. Mean prostate size at time of RT was 42 ± 21 g. Of the entire population, 72% lost the ability to ejaculate in an antegrade fashion after prostate RT by their last visit. The proportion experiencing anejaculation at 1, 3, and 5 years after RT was 16%, 69%, and 89%, respectively. For men with at least two IIEF questionnaires completed, the orgasm domain scores decreased dramatically over the follow-up period; orgasm domain scores (0-10): <12 months post-RT 7.4, 13-24 months 5.4, 25-36 months 3.2, >36 months 2.8 (P < 0.01). Multivariable analysis identified several factors predictive of failure to ejaculate: older age, ADT, RT dose > 100 Gy, and smaller prostates at the time of RT. The vast majority of men after prostate RT will experience anejaculation and should be

  15. ¹H NMR-based metabolic profiling of human rectal cancer tissue

    PubMed Central

    2013-01-01

    Background Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. Methods Here, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer. Results Excellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would

  16. Oncogenic mutation profiling in new lung cancer and mesothelioma cell lines

    PubMed Central

    Lam, David CL; Luo, Susan Y; Deng, Wen; Kwan, Johnny SH; Rodriguez-Canales, Jaime; Cheung, Annie LM; Cheng, Grace HW; Lin, Chi-Ho; Wistuba, Ignacio I; Sham, Pak C; Wan, Thomas SK; Tsao, Sai-Wah

    2015-01-01

    Background Thoracic tumor, especially lung cancer, ranks as the top cancer mortality in most parts of the world. Lung adenocarcinoma is the predominant subtype and there is increasing knowledge on therapeutic molecular targets, namely EGFR, ALK, KRAS, and ROS1, among lung cancers. Lung cancer cell lines established with known clinical characteristics and molecular profiling of oncogenic targets like ALK or KRAS could be useful tools for understanding the biology of known molecular targets as well as for drug testing and screening. Materials and methods Five new cancer cell lines were established from pleural fluid or biopsy tissues obtained from Chinese patients with primary lung adenocarcinomas or malignant pleural mesothelioma. They were characterized by immunohistochemistry, growth kinetics, tests for tumorigenicity, EGFR and KRAS gene mutations, ALK gene rearrangement and OncoSeq mutation profiling. Results These newly established lung adenocarcinoma and mesothelioma cell lines were maintained for over 100 passages and demonstrated morphological and immunohistochemical features as well as growth kinetics of tumor cell lines. One of these new cell lines bears EML4-ALK rearrangement variant 2, two lung cancer cell lines bear different KRAS mutations at codon 12, and known single nucleotide polymorphism variants were identified in these cell lines. Discussion Four new lung adenocarcinoma and one mesothelioma cell lines were established from patients with different clinical characteristics and oncogenic mutation profiles. These characterized cell lines and their mutation profiles will provide resources for exploration of lung cancer and mesothelioma biology with regard to the presence of known oncogenic mutations. PMID:25653542

  17. Family's difficulty scale in end-of-life home care: a new measure of the family's difficulties in caring for patients with cancer at the end of life at home from bereaved family's perspective.

    PubMed

    Ishii, Yoko; Miyashita, Mitsunori; Sato, Kazuki; Ozawa, Taketoshi

    2012-02-01

    The aim of this study was to develop a tool to measure the family's difficulties in caring for cancer patients at the end of life at home: Family's Difficulty Scale in end-of-life home care (FDS). The draft of the FDS was derived from a pilot interview survey and literature reviews. The questionnaires were sent to 395 bereaved family caregivers whose family members were patients with terminal cancer receiving home service. We obtained 306 responses (response rate, 81%). Factor analysis resulted in 29 items and 8 factors: Burden of Care, Concerns about Home Care Doctor, Balance of Work and Care, Patient's Pain and Condition, Concerns about Visiting Nurse, Concerns about Home Care Service, Relationship between Family Caregivers and their Families, and Funeral Preparations. The cumulative rate of contribution was 71.8%. Cronbach coefficient α for the FDS was 0.73-0.75; the intraclass correlation coefficient in the test-retest examination was 0.75-0.85. Evidence for construct validity was confirmed by convergent and divergent validity. Concurrent validity was confirmed by significant correlations between identified factors and concurrent measures. The validity and reliability of this new instrument were confirmed. This scale should help home care providers to assess and focus on family difficulties and provide individualized care for the family who cares for a patient with terminal cancer at home.

  18. Functioning and health in patients with cancer on home-parenteral nutrition: a qualitative study

    PubMed Central

    2010-01-01

    Background Malnutrition is a common problem in patients with cancer. One possible strategy to prevent malnutrition and further deterioration is to administer home-parenteral nutrition (HPN). While the effect on survival is still not clear, HPN presumably improves functioning and quality of life. Thus, patients' experiences concerning functioning and quality of life need to be considered when deciding on the provision of HPN. Currently used quality of life measures hardly reflect patients' perspectives and experiences. The objective of our study was to investigate the perspectives of patients with cancer on their experience of functioning and health in relation to HPN in order to get an item pool to develop a comprehensive measure to assess the impact of HPN in this population. Methods We conducted a series of qualitative semi-structured interviews. The interviews were analysed to identify categories of the International Classification of Functioning, Disability and Health (ICF) addressed by patients' statements. Patients were consecutively included in the study until an additional patient did not yield any new information. Results We extracted 94 different ICF-categories from 16 interviews representing patient-relevant aspects of functioning and health (32 categories from the ICF component 'Body Functions', 10 from 'Body Structures', 32 from 'Activities & Participation', 18 from 'Environmental Factors'). About 8% of the concepts derived from the interviews could not be linked to specific ICF categories because they were either too general, disease-specific or pertained to 'Personal Factors'. Patients referred to 22 different aspects of functioning improving due to HPN; mainly activities of daily living, mobility, sleep and emotional functions. Conclusions The ICF proved to be a satisfactory framework to standardize the response of patients with cancer on HPN. For most aspects reported by the patients, a matching concept and ICF category could be found. The

  19. Biomechanical profile of cancer stem-like/tumor-initiating cells derived from a progressive ovarian cancer model.

    PubMed

    Babahosseini, Hesam; Ketene, Alperen N; Schmelz, Eva M; Roberts, Paul C; Agah, Masoud

    2014-07-01

    We herein report, for the first time, the mechanical properties of ovarian cancer stem-like/tumor-initiating cells (CSC/TICs). The represented model is a spontaneously transformed murine ovarian surface epithelial (MOSE) cell line that mimics the progression of ovarian cancer from early/non-tumorigenic to late/highly aggressive cancer stages. Elastic modulus measurements via atomic force microscopy (AFM) illustrate that the enriched CSC/TICs population (0.32±0.12kPa) are 46%, 61%, and 72% softer (P<0.0001) than their aggressive late-stage, intermediate, and non-malignant early-stage cancer cells, respectively. Exposure to sphingosine, an anti-cancer agent, induced an increase in the elastic moduli of CSC/TICs by more than 46% (0.47±0.14kPa, P<0.0001). Altogether, our data demonstrate that the elastic modulus profile of CSC/TICs is unique and responsive to anti-cancer treatment strategies that impact the cytoskeleton architecture of cells. These findings increase the chance for obtaining distinctive cell biomechanical profiles with the intent of providing a means for effective cancer detection and treatment control. This novel study utilized atomic force microscopy to demonstrate that the elastic modulus profile of cancer stem cell-like tumor initiating cells is unique and responsive to anti-cancer treatment strategies that impact the cytoskeleton of these cells. These findings pave the way to the development of unique means for effective cancer detection and treatment control. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Whole-Body Profiling of Cancer Metastasis with Single-Cell Resolution.

    PubMed

    Kubota, Shimpei I; Takahashi, Kei; Nishida, Jun; Morishita, Yasuyuki; Ehata, Shogo; Tainaka, Kazuki; Miyazono, Kohei; Ueda, Hiroki R

    2017-07-05

    Stochastic and proliferative events initiated from a single cell can disrupt homeostatic balance and lead to fatal disease processes such as cancer metastasis. To overcome metastasis, it is necessary to detect and quantify sparsely distributed metastatic cells throughout the body at early stages. Here, we demonstrate that clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC)-based cancer (CUBIC-cancer) analysis with a refractive index (RI)-optimized protocol enables comprehensive cancer cell profiling of the whole body and organs. We applied CUBIC-cancer analysis to 13 mouse models using nine cancer cell lines and spatiotemporal quantification of metastatic cancer progression at single-cell resolution. CUBIC-cancer analysis suggests that the epithelial-mesenchymal transition promotes not only extravasation but also cell survival at metastatic sites. CUBIC-cancer analysis is also applicable to pharmacotherapeutic profiling of anti-tumor drugs. CUBIC-cancer analysis is compatible with in vivo bioluminescence imaging and 2D histology. We suggest that a scalable analytical pipeline with these three modalities may contribute to addressing currently incurable metastatic diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  1. Lung Cancer Signatures in Plasma Based on Proteome Profiling of Mouse Tumor Models

    PubMed Central

    Taguchi, Ayumu; Politi, Katerina; Pitteri, Sharon J.; Lockwood, William W.; Faça, Vitor M.; Kelly-Spratt, Karen; Wong, Chee-Hong; Zhang, Qing; Chin, Alice; Park, Kwon-Sik; Goodman, Gary; Gazdar, Adi F.; Sage, Julien; Dinulescu, Daniela M.; Kucherlapati, Raju; DePinho, Ronald A.; Kemp, Christopher J.; Varmus, Harold E.; Hanash, Samir M.

    2012-01-01

    SUMMARY We investigated the potential of in-depth quantitative proteomics to reveal plasma protein signatures that reflect lung tumor biology. We compared plasma protein profiles of four mouse models of lung cancer with profiles of models of pancreatic, ovarian, colon, prostate, and breast cancer and two models of inflammation. A protein signature for Titf1/Nkx2-1, a known lineage-survival oncogene in lung cancer, was found in plasmas of mouse models of lung adenocarcinoma. An EGFR signature was found in plasma of an EGFR mutant model, and a distinct plasma signature related to neuroendocrine development was uncovered in the small-cell lung cancer model. We demonstrate relevance to human lung cancer of the protein signatures identified on the basis of mouse models. PMID:21907921

  2. Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies

    PubMed Central

    Darby, S; Hill, D; Auvinen, A; Barros-Dios, J M; Baysson, H; Bochicchio, F; Deo, H; Falk, R; Forastiere, F; Hakama, M; Heid, I; Kreienbrock, L; Kreuzer, M; Lagarde, F; Mäkeläinen, I; Muirhead, C; Oberaigner, W; Pershagen, G; Ruano-Ravina, A; Ruosteenoja, E; Rosario, A Schaffrath; Tirmarche, M; Tomášek, L; Whitley, E; Wichmann, H-E; Doll, R

    2005-01-01

    Objective To determine the risk of lung cancer associated with exposure at home to the radioactive disintegration products of naturally occurring radon gas Design Collaborative analysis of individual data from 13 case-control studies of residential radon and lung cancer. Setting Nine European countries. Subjects 7148 cases of lung cancer and 14 208 controls. Main outcome measures Relative risks of lung cancer and radon gas concentrations in homes inhabited during the previous 5-34 years measured in becquerels (radon disintegrations per second) per cubic metre (Bq/m3) of household air. Results The mean measured radon concentration in homes of people in the control group was 97 Bq/m3, with 11% measuring > 200 and 4% measuring > 400 Bq/m3. For cases of lung cancer the mean concentration was 104 Bq/m3. The risk of lung cancer increased by 8.4% (95% confidence interval 3.0% to 15.8%) per 100 Bq/m3 increase in measured radon (P = 0.0007). This corresponds to an increase of 16% (5% to 31%) per 100 Bq/m3 increase in usual radon—that is, after correction for the dilution caused by random uncertainties in measuring radon concentrations. The dose-response relation seemed to be linear with no threshold and remained significant (P = 0.04) in analyses limited to individuals from homes with measured radon < 200 Bq/m3. The proportionate excess risk did not differ significantly with study, age, sex, or smoking. In the absence of other causes of death, the absolute risks of lung cancer by age 75 years at usual radon concentrations of 0, 100, and 400 Bq/m3 would be about 0.4%, 0.5%, and 0.7%, respectively, for lifelong non-smokers, and about 25 times greater (10%, 12%, and 16%) for cigarette smokers. Conclusions Collectively, though not separately, these studies show appreciable hazards from residential radon, particularly for smokers and recent ex-smokers, and indicate that it is responsible for about 2% of all deaths from cancer in Europe. PMID:15613366

  3. The Liverpool Care Pathway: a systematic review discarded in cancer patients but good enough for dying nursing home patients?

    PubMed

    Husebø, Bettina S; Flo, Elisabeth; Engedal, Knut

    2017-08-09

    The Liverpool Care Pathway (LCP) is an interdisciplinary protocol, aiming to ensure that dying patients receive dignified and individualized treatment and care at the end-of-life. LCP was originally developed in 1997 in the United Kingdom from a model of cancer care successfully established in hospices. It has since been introduced in many countries, including Norway. The method was withdrawn in the UK in 2013. This review investigates whether LCP has been adapted and validated for use in nursing homes and for dying people with dementia. This systematic review is based on a systematic literature search of MEDLINE, CINAHL, EMBASE, and Web of Science. The search identified 12 studies, but none describing an evidence-based adaption of LCP to nursing home patients and people with dementia. No studies described the LCP implementation procedure, including strategies for discontinuation of medications, procedures for nutrition and hydration, or the testing of such procedures in nursing homes. No effect studies addressing the assessment and treatment of pain and symptoms that include dying nursing home patients and people with dementia are available. LCP has not been adapted to nursing home patients and people with dementia. Current evidence, i.e. studies investigating the validity and reliability in clinically relevant settings, is too limited for the LCP procedure to be recommended for the population at hand. There is a need to develop good practice in palliative medicine, Advance Care Planning, and disease-specific recommendations for people with dementia.

  4. Identification of circadian-related gene expression profiles in entrained breast cancer cell lines.

    PubMed

    Gutiérrez-Monreal, Miguel A; Treviño, Victor; Moreno-Cuevas, Jorge E; Scott, Sean-Patrick

    2016-01-01

    Cancer cells have broken circadian clocks when compared to their normal tissue counterparts. Moreover, it has been shown in breast cancer that disruption of common circadian oscillations is associated with a more negative prognosis. Numerous studies, focused on canonical circadian genes in breast cancer cell lines, have suggested that there are no mRNA circadian-like oscillations. Nevertheless, cancer cell lines have not been extensively characterized and it is unknown to what extent the circadian oscillations are disrupted. We have chosen representative non-cancerous and cancerous breast cell lines (MCF-10A, MCF-7, ZR-75-30, MDA-MB-231 and HCC-1954) in order to determine the degree to which the circadian clock is damaged. We used serum shock to synchronize the circadian clocks in culture. Our aim was to initially observe the time course of gene expression using cDNA microarrays in the non-cancerous MCF-10A and the cancerous MCF-7 cells for screening and then to characterize specific genes in other cell lines. We used a cosine function to select highly correlated profiles. Some of the identified genes were validated by quantitative polymerase chain reaction (qPCR) and further evaluated in the other breast cancer cell lines. Interestingly, we observed that breast cancer and non-cancerous cultured cells are able to generate specific circadian expression profiles in response to the serum shock. The rhythmic genes, suggested via microarray and measured in each particular subtype, suggest that each breast cancer cell type responds differently to the circadian synchronization. Future results could identify circadian-like genes that are altered in breast cancer and non-cancerous cells, which can be used to propose novel treatments. Breast cell lines are potential models for in vitro studies of circadian clocks and clock-controlled pathways.

  5. Multivariate classification of urine metabolome profiles for breast cancer diagnosis.

    PubMed

    Kim, Younghoon; Koo, Imhoi; Jung, Byung Hwa; Chung, Bong Chul; Lee, Doheon

    2010-04-16

    Diagnosis techniques using urine are non-invasive, inexpensive, and easy to perform in clinical settings. The metabolites in urine, as the end products of cellular processes, are closely linked to phenotypes. Therefore, urine metabolome is very useful in marker discoveries and clinical applications. However, only univariate methods have been used in classification studies using urine metabolome. Since multiple genes or proteins would be involved in developments of complex diseases such as breast cancer, multiple compounds including metabolites would be related with the complex diseases, and multivariate methods would be needed to identify those multiple metabolite markers. Moreover, because combinatorial effects among the markers can seriously affect disease developments and there also exist individual differences in genetic makeup or heterogeneity in cancer progressions, single marker is not enough to identify cancers. We proposed classification models using multivariate classification techniques and developed an analysis procedure for classification studies using metabolome data. Through this strategy, we identified five potential urinary biomarkers for breast cancer with high accuracy, among which the four biomarker candidates were not identifiable by only univariate methods. We also proposed potential diagnosis rules to help in clinical decision making. Besides, we showed that combinatorial effects among multiple biomarkers can enhance discriminative power for breast cancer. In this study, we successfully showed that multivariate classifications are needed to precisely diagnose breast cancer. After further validation with independent cohorts and experimental confirmation, these marker candidates will likely lead to clinically applicable assays for earlier diagnoses of breast cancer.

  6. A Classification Framework Applied to Cancer Gene Expression Profiles

    PubMed Central

    Hijazi, Hussein; Chan, Christina

    2013-01-01

    Classification of cancer based on gene expression has provided insight into possible treatment strategies. Thus, developing machine learning methods that can successfully distinguish among cancer subtypes or normal versus cancer samples is important. This work discusses supervised learning techniques that have been employed to classify cancers. Furthermore, a two-step feature selection method based on an attribute estimation method (e.g., ReliefF) and a genetic algorithm was employed to find a set of genes that can best differentiate between cancer subtypes or normal versus cancer samples. The application of different classification methods (e.g., decision tree, k-nearest neighbor, support vector machine (SVM), bagging, and random forest) on 5 cancer datasets shows that no classification method universally outperforms all the others. However, k-nearest neighbor and linear SVM generally improve the classification performance over other classifiers. Finally, incorporating diverse types of genomic data (e.g., protein-protein interaction data and gene expression) increase the prediction accuracy as compared to using gene expression alone. PMID:23778014

  7. Proteomic technology for biomarker profiling in cancer: an update*

    PubMed Central

    Alaoui-Jamali, Moulay A.; Xu, Ying-jie

    2006-01-01

    The progress in the understanding of cancer progression and early detection has been slow and frustrating due to the complex multifactorial nature and heterogeneity of the cancer syndrome. To date, no effective treatment is available for advanced cancers, which remain a major cause of morbidity and mortality. Clearly, there is urgent need to unravel novel biomarkers for early detection. Most of the functional information of the cancer-associated genes resides in the proteome. The later is an exceptionally complex biological system involving several proteins that function through posttranslational modifications and dynamic intermolecular collisions with partners. These protein complexes can be regulated by signals emanating from cancer cells, their surrounding tissue microenvironment, and/or from the host. Some proteins are secreted and/or cleaved into the extracellular milieu and may represent valuable serum biomarkers for diagnosis purpose. It is estimated that the cancer proteome may include over 1.5 million proteins as a result of posttranslational processing and modifications. Such complexity clearly highlights the need for ultra-high resolution proteomic technology for robust quantitative protein measurements and data acquisition. This review is to update the current research efforts in high-resolution proteomic technology for discovery and monitoring cancer biomarkers. PMID:16625706

  8. Mass Spectrometry–based Proteomic Profiling of Lung Cancer

    PubMed Central

    Ocak, Sebahat; Chaurand, Pierre; Massion, Pierre P.

    2009-01-01

    In an effort to further our understanding of lung cancer biology and to identify new candidate biomarkers to be used in the management of lung cancer, we need to probe these tissues and biological fluids with tools that address the biology of lung cancer directly at the protein level. Proteins are responsible of the function and phenotype of cells. Cancer cells express proteins that distinguish them from normal cells. Proteomics is defined as the study of the proteome, the complete set of proteins produced by a species, using the technologies of large-scale protein separation and identification. As a result, new technologies are being developed to allow the rapid and systematic analysis of thousands of proteins. The analytical advantages of mass spectrometry (MS), including sensitivity and high-throughput, promise to make it a mainstay of novel biomarker discovery to differentiate cancer from normal cells and to predict individuals likely to develop or recur with lung cancer. In this review, we summarize the progress made in clinical proteomics as it applies to the management of lung cancer. We will focus our discussion on how MS approaches may advance the areas of early detection, response to therapy, and prognostic evaluation. PMID:19349484

  9. Enhanced Baculovirus-Mediated Transduction of Human Cancer Cells by Tumor-Homing Peptides

    PubMed Central

    Mäkelä, Anna R.; Matilainen, Heli; White, Daniel J.; Ruoslahti, Erkki; Oker-Blom, Christian

    2006-01-01

    Tumor cells and vasculature offer specific targets for the selective delivery of therapeutic genes. To achieve tumor-specific gene transfer, baculovirus tropism was manipulated by viral envelope modification using baculovirus display technology. LyP-1, F3, and CGKRK tumor-homing peptides, originally identified by in vivo screening of phage display libraries, were fused to the transmembrane anchor of vesicular stomatitis virus G protein and displayed on the baculoviral surface. The fusion proteins were successfully incorporated into budded virions, which showed two- to fivefold-improved binding to human breast carcinoma (MDA-MB-435) and hepatocarcinoma (HepG2) cells. The LyP-1 peptide inhibited viral binding to MDA-MB-435 cells with a greater magnitude and specificity than the CGKRK and F3 peptides. Maximal 7- and 24-fold increases in transduction, determined by transgene expression level, were achieved for the MDA-MB-435 and HepG2 cells, respectively. The internalization of each virus was inhibited by ammonium chloride treatment, suggesting the use of a similar endocytic entry route. The LyP-1 and F3 peptides showed an apparent inhibitory effect in transduction of HepG2 cells with the corresponding display viruses. Together, these results imply that the efficiency of baculovirus-mediated gene delivery can be significantly enhanced in vitro when tumor-targeting ligands are used and therefore highlight the potential of baculovirus vectors in cancer gene therapy. PMID:16775347

  10. Evaluation of electronic patient-reported outcome assessment with cancer patients in the hospital and at home.

    PubMed

    Wintner, L M; Giesinger, J M; Zabernigg, A; Rumpold, G; Sztankay, M; Oberguggenberger, A S; Gamper, E M; Holzner, B

    2015-12-23

    Patient-reported outcomes (PRO) provide a more comprehensive picture of patients' quality of life than do mere physicians' ratings. Electronic data collection of PRO offers several advantages and allows assessments at patients' homes as well. This study reports on patients' personal internet use, their attitudes towards electronic and web-based PRO assessment (clinic-ePRO and home-ePRO) and the feasibility of these two assessment modes. At the Medical University of Innsbruck and Kufstein County Hospital, cancer patients who participated in clinic-ePRO/home-ePRO were asked to complete a comprehensive evaluation form on their personal internet usage, attitudes towards and the feasibility of routine clinic-ePRO/home-ePRO with the Computer-based Health Evaluation System (CHES) software. In total, 113 patients completed the evaluation form for clinic-ePRO (Ø 45 years, SD 14) and 45 patients for home-ePRO (Ø 58 years, SD 10; 33.1 per cent inclusion rate for this sample). Most patients expressed willingness to complete routine clinic-ePRO assessments in the future (94.7 per cent of clinic-ePRO patients and 84.4 per cent of home-ePRO patients) and to discuss their data with attending physicians (82.2 per cent, home-ePRO patients only). Overall, patients preferred the software over paper-pencil questionnaires (67.2 per cent of clinic-ePRO patients and 60 per cent of home-ePRO patients) and experienced it as easy to use. Only a few minor suggestions for improvement were made (e.g. adjustable font sizes). The use of clinic-ePRO/home-ePRO was in general shown to be feasible and well accepted. However, to be more inclusive in the implementation of clinic-ePRO/home-ePRO, educational programs concerning their particular benefit in oncology practice potentially could enhance patients' attitudes towards, and consequently their acceptance of and compliance with electronic PRO assessments.

  11. [Stimulation at home and psychological profile of mothers of children with or without weight loss during the first 15 days of life].

    PubMed

    Bravo, G; Cravioto, J; Cravioto, P; Fernández, G

    1990-04-01

    To determine the possible difference of the microenvironment of a group of children who lost weight in their first 15 days of life. Longitudinal ecological study of growth and development of a total cohort of all children born during a calendar year. Rural village of Central Mexico. A group of sixteen children, who fifteen days after birth and without apparent reason, showed a decrease in weight as compared with weight at birth, they were compared with a control group from the same population and matched, case by case, according to gestation age, height at the time of birth, and body weight. To assess the influence of microenvironmental factors two indicators were used. Recording and scoring of maternal behavior was done by adaptation to local conditions by Cravioto et al, of the Maternal Behavior Profile developed by Nancy Bayley. The instrument used for estimating home stimulation was the inventory developed by Caldwell design to sample certain aspects of the quantity and/quality of social, emotional, and cognitive stimulation available to a young child within his home. No significant differences were found in relation to Maternal Behavior Profile and Home Stimulation in the two groups studied (statistical differences, P greater than 0.05). Data from present study contribute to the claim that systematic stimulation in the home and an adequate interrelation mother-child are among the main elements necessary for the proper development of the child.

  12. Determinants of Anti-Cancer Effect of Mitochondrial Electron Transport Chain Inhibitors: Bioenergetic Profile and Metabolic Flexibility of Cancer Cells.

    PubMed

    Urra, Félix A; Weiss-López, Boris; Araya-Maturana, Ramiro

    2016-01-01

    Recent evidence highlights that energy requirements of cancer cells vary greatly from normal cells and they exhibit different metabolic phenotypes with variable participation of both glycolysis and oxidative phosphorylation (OXPHOS). Interestingly, mitochondrial electron transport chain (ETC) has been identified as an essential component in bioenergetics, biosynthesis and redox control during proliferation and metastasis of cancer cells. This dependence converts ETC of cancer cells in a promising target to design small molecules with anti-cancer actions. Several small molecules have been described as ETC inhibitors with different consequences on mitochondrial bioenergetics, viability and proliferation of cancer cells, when the substrate availability is controlled to favor either the glycolytic or OXPHOS pathway. These ETC inhibitors can be grouped as 1) inhibitors of a respiratory complex (e.g. rotenoids, vanilloids, alkaloids, biguanides and polyphenols), 2) inhibitors of several respiratory complexes (e.g. capsaicin, ME-344 and epigallocatechin-3 gallate) and 3) inhibitors of ETC activity (e.g. elesclomol and VLX600). Although pharmacological ETC inhibition may produce cell death and a decrease of proliferation of cancer cells, factors such as degree of inhibition of ETC activity by small molecules, bioenergetic profile and metabolic flexibility of different cancer types or subpopulations of cells in a particular cancer type, can affect the impact of the anti-cancer actions. Particularly interesting are the adaptive mechanisms induced by ETC inhibition, such as induction of glutamine-dependent reductive carboxylation, which may offer a strategy to sensitize cancer cells to inhibitors of glutamine metabolism.

  13. Protein and lipid MALDI profiles classify breast cancers according to the intrinsic subtype

    PubMed Central

    2011-01-01

    Background Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) has been demonstrated to be useful for molecular profiling of common solid tumors. Using recently developed MALDI matrices for lipid profiling, we evaluated whether direct tissue MALDI MS analysis on proteins and lipids may classify human breast cancer samples according to the intrinsic subtype. Methods Thirty-four pairs of frozen, resected breast cancer and adjacent normal tissue samples were analyzed using histology-directed, MALDI MS analysis. Sinapinic acid and 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. Results Protein and lipid profiles distinguish cancer from adjacent normal tissue samples with the median prediction accuracy of 94.1%. Luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by permutation P values less than 0.01 for 0.632+ bootstrap cross-validated misclassification rates with all classifiers tested. Discriminatory proteins and lipids were useful for classifying tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in random test sets. Conclusions Protein and lipid profiles accurately distinguish tumor from adjacent normal tissue and classify breast cancers according to the intrinsic subtype. PMID:22029885

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

    PubMed

    Zardavas, Dimitrios; Piccart-Gebhart, Martine

    2015-01-01

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

  15. Genomic profiling of circulating plasma RNA for the analysis of cancer.

    PubMed

    Collado, Manuel; Garcia, Vanesa; Garcia, Jose Miguel; Alonso, Isabel; Lombardia, Luis; Diaz-Uriarte, Ramon; Fernández, Luis A López; Zaballos, Angel; Bonilla, Félix; Serrano, Manuel

    2007-10-01

    The blood of cancer patients is known to contain fragments of RNA released from the tumor. The application of genomic profiling techniques to plasma RNA may allow the unbiased selection of cancer markers in the blood, but the informative value of genomic profiling of plasma RNA is currently unknown. We used cDNA microarray hybridization to perform genomic profiling of plasma RNA from colorectal cancer (CRC) patients and from healthy donors. From a list of 40 genes differentially upregulated in cancer patients, we randomly selected 4 genes for further characterization. These 4 markers were analyzed by quantitative reverse-transcription PCR in a wide set of samples including paired samples from the same CRC patients before and after surgical resection of the tumor. Three of the selected markers - EPAS1, UBE2D3, and KIAA0101 - were confirmed by PCR to be significantly increased in cancer compared to healthy donors. Importantly, 2 of the markers, EPAS1 and UBE2D3, showed a significant decrease after surgery, returning to the levels of healthy donors. Finally, supervised class prediction using these 3 markers correctly (77%) assigned presurgery samples to the CRC group and assigned postsurgery samples from the same patients to the healthy group. Our findings demonstrate the usefulness of gene expression profiling of circulating plasma RNA to find cancer markers of potential clinical value.

  16. The role of developing breast cancer in alteration of serum lipid profile

    PubMed Central

    Abdelsalam, Kamal Eldin A.; Hassan, Ikhlas K.; Sadig, Isam A.

    2012-01-01

    Aims: The major aim of this study is to examine the role of alterations in lipid profile in women developing breast cancer. This study was carried out between May 2009 and December 2010. Background: The relationship between lipids and breast cancer is undistinguished. Until now, conflicting results have been reported on the association between lipids and risk of breast cancer development in women. Materials and Methods: Plasma lipids (i.e., total cholesterol [TC], high-density lipoprotein [HDL], low-density lipoprotein [LDL], and triglycerides [TG] were analyzed from 60 controls and 120 untreated breast cancer patients with clinical and histopathological evidence, under aseptic conditions. Venous blood was drawn from the cases and controls and estimations of lipid profile were done utilizing the standard procedures. Statistical Analysis Used: Independent sample t-test to compare the mean serum levels of lipid profile and TC/HDL ratio between patients and controls. Results: A significant rise in serum total cholesterol, low-density lipoprotein cholesterol, and ratio of total cholesterol: high density lipoprotein cholesterol values, whereas high density lipoprotein cholesterol and very low density lipoprotein cholesterol were not affected significantly by the breast cancer. Conclusions: The developing breast cancer might be considered as one of the factors in alterations in lipid profile levels. PMID:23626635

  17. Blood Peptidome-Degradome Profile of Breast Cancer

    SciTech Connect

    Shen, Yufeng; Tolic, Nikola; Liu, Tao; Zhao, Rui; Petritis, Brianne O; Gritsenko, Marina A; Camp, David G; Moore, Ronald J; Purvine, Samuel O; Esteva, FJ; Smith, Richard D

    2010-10-18

    We report on the degradomic-peptidomic insights into blood plasma of early-stage breast cancer patients. The plasmin-α2-antiplasmin and thrombin-antithrombin systems are observed to be changed in early stage breast cancer through the selective degradation of their functional domains. The extracellular matrix (ECM) protection protein complexes are destroyed, but the ECM itself is not massively degraded. Key innate immune system components and cancer inhibitor and suppressor substrates are differentially degraded. The degradomic-peptidomic analysis provides information on the selectivity and extent of substrate and functional domain degradation and the specificity of substrate cleavages, potentially enabling discovery of diagnostic and therapeutic targets for early-stage breast cancer.

  18. Metabolomic Profiling of Prostate Cancer Progression During Active Surveillance

    DTIC Science & Technology

    2015-10-01

    collected under a separate ongoing protocol of Dr. Trock’s, WIRB protocol #20011642 “Molecular Epidemiology of Prostate Cancer.” This protocol also...PhD, and WIRB protocol #20011642 “Molecular Epidemiology of Prostate Cancer”, PI: Bruce Trock, PhD. Dr. Trock obtained tissues from these...and Evaluation of a Tumor Marker for Prostate Cancer “ (PI: Alan Partin, MD, PhD), and under WIRB protocol #20011642 “Molecular Epidemiology of

  19. Recent Advances in Metabolic Profiling And Imaging of Prostate Cancer

    PubMed Central

    Thapar, Roopa; Titus, Mark A

    2015-01-01

    Cancer is a metabolic disease. Cancer cells, being highly proliferative, show significant alterations in metabolic pathways such as glycolysis, respiration, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, lipid metabolism, and amino acid metabolism. Metabolites like peptides, nucleotides, products of glycolysis, the TCA cycle, fatty acids, and steroids can be an important read out of disease when characterized in biological samples such as tissues and body fluids like urine, serum, etc. The cancer metabolome has been studied since the 1960s by analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Current research is focused on the identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients and distinguish between benign and advanced metastatic forms of the disease. In this review, we discuss the current state of prostate cancer metabolomics, the biomarkers that show promise in distinguishing indolent from aggressive forms of the disease, the strengths and limitations of the analytical techniques being employed, and future applications of metabolomics in diagnostic imaging and personalized medicine of prostate cancer. PMID:25632377

  20. Serum lipid profile in oral cancer and leukoplakia: correlation with tobacco abuse and histological grading.

    PubMed

    Kumar, Priya; Augustine, J; Urs, Aadithya B; Arora, Shelly; Gupta, Shalini; Mohanty, Vikrant R

    2012-01-01

    Role of alterations in serum lipid profile in oral cancer remains controversial. The present study aimed to evaluate the implications of altered serum lipid profile in patients with oral cancer (OC), oral leukoplakia (OLP), and tobacco habits. Thirty patients with OC, 30 with OLP, 30 tobacco abusers (TAs), and 30 age and sex matched healthy controls were included in the study. Serum lipid profile including total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), Very low density lipoprotein (VLDL), and triglycerides (Tg) were evaluated using a fully automatic Biochemistry analyzer. Difference in lipid profile in various types of TA, that is, smokeless tobacco (SLT), smoking tobacco (ST), and a combination (Comb) usage of both forms were also analyzed. TC, HDL, and LDL were much lower in the OC group compared with control. Although these parameters were low in the OPC group compared with controls, the difference was not significant. On histological analysis, TC and HDL were found to decrease marginally with loss of tumor differentiation in OC. No correlation was found between the mean serum lipid profiles and degree of dysplasia in OLP. TC and HDL were significantly lesser in all forms of TA when compared with control. There may be an inverse relationship between serum lipid profile and OC. No significant reduction in lipid profile was observed in the OLP group. This may indicate that hypolipidemia is a late change occurring during carcinogenesis or is an effect rather than the cause of cancer.

  1. Home-Based Palliative Care for Children With Incurable Cancer: Long-term Perspectives of and Impact on General Practitioners.

    PubMed

    van der Geest, Ivana M M; Bindels, Patrick J E; Pluijm, Saskia M F; Michiels, Erna M C; van der Heide, Agnes; Pieters, Rob; Darlington, Anne-Sophie E; van den Heuvel-Eibrink, Marry M

    2017-03-01

    Although a large percentage of children with advanced-stage cancer die at home, remarkably little information is available regarding the experience of general practitioners (GPs) with respect to providing home-based palliative care to children with incurable cancer. The objective of this study was to explore the perspectives of GPs who care for children with advanced-stage cancer in a home-based setting. In this cross-sectional study, 144 GPs who provided home-based palliative care to 150 children with incurable cancer from 2001 through 2010 were invited to complete a questionnaire addressing their perspectives regarding: 1) symptom management, 2) collaboration with other health care professionals, 3) the child's death and care after death, and 4) impact of having provided palliative care, scored on distress thermometer (range 0-10). A total of 112 GPs (78%) responded, and 91 GPs completed the questionnaire for 93 patients. The median interval between the child's death and completing the questionnaire was seven years. The most prevalent symptoms reported in the patients were fatigue (67%) and pain (61%). Difficulties with communicating with (14%), coordinating with (11%), collaborating with (11%), and contacting (2%) fellow members of the multidisciplinary treatment team were rare. Hectic (7%) and shocking (5%) situations and panic (2%) around the child's death were rare. GPs reported feelings of sadness (61%) and/or powerlessness (43%) around the time of the patient's death, and they rated their own distress level as relatively high during the terminal phase (median score 6, range 0-9.5). The majority of GPs (94%) reported that they ultimately came to terms with the child's death. In general, GPs appear to be satisfied with the quality of home-based palliative care that they provide pediatric patients with incurable cancer. Communication among health care professionals is generally positive and is considered important. Finally, although the death of a pediatric

  2. Gene profile identifies zinc transporters differentially expressed in normal human organs and human pancreatic cancer.

    PubMed

    Yang, J; Zhang, Y; Cui, X; Yao, W; Yu, X; Cen, P; Hodges, S E; Fisher, W E; Brunicardi, F C; Chen, C; Yao, Q; Li, M

    2013-03-01

    Deregulated expression of zinc transporters was linked to several cancers. However, the detailed expression profile of all human zinc transporters in normal human organs and in human cancer, especially in pancreatic cancer is not available. The objectives of this study are to investigate the complete expression patterns of 14 ZIP and 10 ZnT transporters in a large number of normal human organs and in human pancreatic cancer tissues and cell lines. We examined the expression patterns of ZIP and ZnT transporters in 22 different human organs and tissues, 11 pairs of clinical human pancreatic cancer specimens and surrounding normal/benign tissues, as well as 10 established human pancreatic cancer cell lines plus normal human pancreatic ductal epithelium (HPDE) cells, using real time RT-PCR and immunohistochemistry. The results indicate that human zinc transporters have tissue specific expression patterns, and may play different roles in different organs or tissues. Almost all the ZIPs except for ZIP4, and most ZnTs were down-regulated in human pancreatic cancer tissues compared to the surrounding benign tissues. The expression patterns of individual ZIPs and ZnTs are similar among different pancreatic cancer lines. Those results and our previous studies suggest that ZIP4 is the only zinc transporter that is significantly up-regulated in human pancreatic cancer and might be the major zinc transporter that plays an important role in pancreatic cancer growth. ZIP4 might serve as a novel molecular target for pancreatic cancer diagnosis and therapy.

  3. A profile of cancer patient outcomes from a tertiary care teaching hospital in Malaysia.

    PubMed

    Suthahar, A; Gurpreet, K; Ambigga, D; Maniam, T; Dhachayani, S; Fuad, I; Adlina, S

    2009-07-01

    The aim of this paper was to determine the sociodemographic and cancer characteristics of patients with cancer at a tertiary care centre. For the study, 80 newly-diagnosed cancer patients were selected and interviewed using structured questionnaires that included sociodemographic and cancer characteristic profiles. At the end of the study period of two years, the survivorship status of the patients was determined. Gender, occupational status, type of cancer and stage of cancer were found to be significantly associated with the survival status among the study group of cancer patients. Results of logistic regression analysis showed that deceased patients were significantly more likely to be pensioners rather than employed, aged 60-69 years rather than 40-49 years, to have all other types of cancer rather than breast cancer, and to be in Stage 3 or 4 of the disease rather than in Stage 1 of the disease. There is a greater necessity for psychosocial research in order to achieve optimal health for patients with cancer, and in turn, to improve the survival of cancer patients.

  4. Breast Cancer Profile among Patients with a History of Chemoprevention

    PubMed Central

    Pivo, Sarah; Refinetti, Ana Paula; Guth, Amber

    2016-01-01

    Purpose. This study identifies women with breast cancer who utilized chemoprevention agents prior to diagnosis and describes their patterns of disease. Methods. Our database was queried retrospectively for patients with breast cancer who reported prior use of chemoprevention. Patients were divided into primary (no history of breast cancer) and secondary (previous history of breast cancer) groups and compared to patients who never took chemoprevention. Results. 135 (6%) of 2430 women used chemoprevention. In the primary chemoprevention group (n = 18, 1%), 39% had completed >5 years of treatment, and fully 50% were on treatment at time of diagnosis. These patients were overwhelmingly diagnosed with ER/PR positive cancers (88%/65%) and were diagnosed with equal percentages (44%) of IDC and DCIS. 117 (87%) used secondary chemoprevention. Patients in this group were diagnosed with earlier stage disease and had lower rates of ER/PR-positivity (73%/65%) than the nonchemoprevention group (84%/72%). In the secondary group, 24% were on chemoprevention at time of diagnosis; 73% had completed >5 years of treatment. Conclusions. The majority of patients who used primary chemoprevention had not completed treatment prior to diagnosis, suggesting that the timing of initiation and compliance to prevention strategies are important in defining the pattern of disease in these patients. PMID:28078143

  5. Breast Cancer Profile among Patients with a History of Chemoprevention.

    PubMed

    Schnabel, Freya R; Pivo, Sarah; Chun, Jennifer; Schwartz, Shira; Refinetti, Ana Paula; Axelrod, Deborah; Guth, Amber

    2016-01-01

    Purpose. This study identifies women with breast cancer who utilized chemoprevention agents prior to diagnosis and describes their patterns of disease. Methods. Our database was queried retrospectively for patients with breast cancer who reported prior use of chemoprevention. Patients were divided into primary (no history of breast cancer) and secondary (previous history of breast cancer) groups and compared to patients who never took chemoprevention. Results. 135 (6%) of 2430 women used chemoprevention. In the primary chemoprevention group (n = 18, 1%), 39% had completed >5 years of treatment, and fully 50% were on treatment at time of diagnosis. These patients were overwhelmingly diagnosed with ER/PR positive cancers (88%/65%) and were diagnosed with equal percentages (44%) of IDC and DCIS. 117 (87%) used secondary chemoprevention. Patients in this group were diagnosed with earlier stage disease and had lower rates of ER/PR-positivity (73%/65%) than the nonchemoprevention group (84%/72%). In the secondary group, 24% were on chemoprevention at time of diagnosis; 73% had completed >5 years of treatment. Conclusions. The majority of patients who used primary chemoprevention had not completed treatment prior to diagnosis, suggesting that the timing of initiation and compliance to prevention strategies are important in defining the pattern of disease in these patients.

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

    PubMed Central

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

    2014-01-01

    Background Technological advances including high-throughput sequencing have identified numerous tumor-specific genetic changes in pediatric and adolescent cancers that can be exploited as targets for novel therapies. Scope of review This review provides a detailed overview of recent advances in the application of target-specific therapies for childhood cancers, either as single agents or in combination with other therapies. The review summarizes preclinical evidence on which clinical trials are based, early phase clinical trial results, and the incorporation of predictive biomarkers into clinical practice, according to cancer type. Major conclusions There is growing evidence that molecularly targeted therapies can valuably add to the arsenal available for treating childhood cancers, particularly when used in combination with other therapies. Nonetheless the introduction of molecularly targeted agents into practice remains challenging, due to the use of unselected populations in some clinical trials, inadequate methods to evaluate efficacy, and the need for improved preclinical models to both evaluate dosing and safety of combination therapies. General significance The increasing recognition of the heterogeneity of molecular causes of cancer favors the continued development of molecularly targeted agents, and their transfer to pediatric and adolescent populations. PMID:26675306

  7. [The university hospital palliative care team's approach to the transfer of end-stage cancer patients from hospital care to home medical care].

    PubMed

    Yoshino, Kazuho; Nishiumi, Noboru; Kushino, Nobuhisa; Tsukada, Michiko; Douzono, Sachiko; Saito, Yuki; Yagame, Mitsunori; Tokuda, Yutaka

    2009-12-01

    The palliative care team's roles are to provide a symptom relief to cancer patients, help them accept their medical conditions, and offer advice regarding the selection of appropriate medical treatments to suit their needs. Seeking the comfort of their homes, patients prefer a home care of superior medical care provided at hospitals. In 2008, 25 of the end-stage cancer patients at hospitals were expressed their desires to have a home medical care, and 10 of them were allowed to do so. We considered the following contributing factors that a patient should have for a smooth transition from hospital care to home medical care: (1) life expectancy of more than 2 months, (2) no progressive breathing difficulties experienced daily, (3) good awareness of medical condition among patients and families, (4) living with someone who has a good understanding of the condition, (5) availability of an appropriate hospital in case of a sudden change in medical requirements, and (6) good collaboration between emergency care hospitals, home physicians, and visiting nurses. To treat the end-stage cancer patients at home, there is a need for information sharing and a joint training of physicians specialized in cancer therapy, palliative care teams, home physicians, and visiting nurses. This would ensure a sustainable "face-to-face collaboration" in community health care.

  8. Utilization and cost of services in the last 6 months of life of patients with cancer - with and without home hospice care.

    PubMed

    Bentur, Netta; Resnizky, Shirli; Balicer, Ran; Eilat-Tsanani, Tsofia

    2014-11-01

    This study examined the utilization and cost of all health services consumed during the last six months of life by cancer patients, and compared those with and without home-hospice care. Detailed information was extracted from the health care electronic administrative data files on 193 deceased cancer patients that their family approved the study (out of 429, 45%). About 88% had been hospitalized for 19 days on average and 53% visited the ER. One quarter received home-hospice care. Their average cost was $13,648 compared to $18,503 for patients without home-hospice care. Hospitalization contributed 32% to the total cost of patients with home-hospice care and 64% for those with it. The findings support the justification for significant expansion of home-hospice care.

  9. Association between Medical Home Enrollment and Health Care Utilization and Costs among Breast Cancer Patients in a State Medicaid Program

    PubMed Central

    Kohler, Racquel E; Goyal, Ravi K; Lich, Kristen Hassmiller; Domino, Marisa Elena; Wheeler, Stephanie B

    2016-01-01

    Background The patient centered medical home (PCMH) is increasingly being implemented in an effort to improve and coordinate primary care, but its effect on health care utilization among breast cancer patients remains unclear. The objective of this study was to examine health care utilization and expenditures as a function of PCMH enrollment among breast cancer patients in North Carolina's Medicaid program. Methods North Carolina Medicaid claims linked to North Carolina Central Cancer Registry records (2003-2007) were used to examine monthly patterns of health care use and expenditures. Fixed effects regression models analyzed associations between PCMH enrollment and utilization of outpatient, inpatient, and emergency department (ED) services and Medicaid expenditures during the 15-months after breast cancer diagnosis, controlling for selection bias on time-invariant characteristics. Results Among 758 breast cancer patients, 381 (50%) were enrolled in a PCMH at some time in the 15 months post-diagnosis. After controlling for individual fixed effects, PCMH enrollment was significantly associated with greater outpatient service use, but there was no difference in the probability of inpatient hospitalizations or ED visits. Enrollment in a PCMH was associated with increased average expenditures of $429 per month during the first 15 months. Conclusions Greater outpatient care utilization and increased average expenditures among breast cancer patients enrolled in a PCMH may suggest that these women have improved access to primary and specialty care. Expanding PCMHs may change patterns of service utilization for Medicaid breast cancer patients, but may not be associated with lower costs. PMID:26287506

  10. Gut flora profiling and fecal metabolite composition of colorectal cancer patients and healthy individuals.

    PubMed

    Wang, Xiaoxue; Wang, Jianping; Rao, Benqiang; Deng, Li

    2017-06-01

    Colorectal cancer is one of the most common types of cancer in the world and its morbidity and mortality rates are increasing due to alterations to human lifestyle and dietary habits. The relationship between human gut flora and colorectal cancer has attracted increasing attention. In the present study, a metabolic fingerprinting technique that combined pyrosequencing with gas chromatography-mass spectrometry was utilized to compare the differences in gut flora profiling and fecal metabolites between healthy individuals and patients with colorectal cancer. The results demonstrated that there were no significant differences in the abundance and diversity of gut flora between healthy individuals and patients with colorectal cancer (P>0.05) and the dominant bacterial phyla present in the gut of both groups included Firmicutes, Bacteroidetes and Verrucomicrobia. At the bacterial strain/genus level, significant differences were observed in the relative abundance of 18 species of bacteria (P<0.05). Analysis of fecal metabolites demonstrated that the metabolic profiles of healthy individuals and patients with colorectal cancer were distinct. The levels of short-chain fatty acid metabolites, including acetic acid, valeric acid, isobutyric acid and isovaleric acid, and of nine amino acids in patients with colorectal cancer were significantly higher than those in healthy individuals (P<0.05). However, the levels of butyrate, oleic acid, trans-oleic acid, linoleic acid, glycerol, monoacyl glycerol, myristic acid, ursodesoxycholic acid and pantothenic acid in patients with colorectal cancer were significantly lower than those in healthy individuals (P<0.05). Pearson rank correlation analysis demonstrated that there was a correlation between gut flora profiling and metabolite composition. These findings suggest that gut flora disorder results in the alteration of bacterial metabolism, which may be associated with the pathogenesis of colorectal cancer. The results of the present

  11. Deciphering Phosphotyrosine-Dependent Signaling Networks in Cancer by SH2 Profiling

    PubMed Central

    Machida, Kazuya; Khenkhar, Malik

    2012-01-01

    It has been a decade since the introduction of SH2 profiling, a modular domain-based molecular diagnostics tool. This review covers the original concept of SH2 profiling, different analytical platforms, and their applications, from the detailed analysis of single proteins to broad screening in translational research. Illustrated by practical examples, we discuss the uniqueness and advantages of the approach as well as its limitations and challenges. We provide guidance for basic researchers and oncologists who may consider SH2 profiling in their respective cancer research, especially for those focusing on tyrosine phosphoproteomics. SH2 profiling can serve as an alternative phosphoproteomics tool to dissect aberrant tyrosine kinase pathways responsible for individual malignancies, with the goal of facilitating personalized diagnostics for the treatment of cancer. PMID:23226573

  12. Profiles of Connectedness: Processes of Resilience and Growth in Children With Cancer.

    PubMed

    Howard Sharp, Katianne M; Willard, Victoria W; Okado, Yuko; Tillery, Rachel; Barnes, Sarah; Long, Alanna; Phipps, Sean

    2015-10-01

    Identified patterns of connectedness in youth with cancer and demographically similar healthy peers. Participants included 153 youth with a history of cancer and 101 youth without a history of serious illness (8-19 years). Children completed measures of connectedness, posttraumatic stress symptoms (PTSS), and benefit-finding. Parents also reported on children's PTSS. Latent profile analysis revealed four profiles: high connectedness (45%), low connectedness (6%), connectedness primarily to parents (40%), and connectedness primarily to peers (9%). These profiles did not differ by history of cancer. However, profiles differed on PTSS and benefit-finding. Children highly connected across domains displayed the lowest PTSS and highest benefit-finding, while those with the lowest connectedness had the highest PTSS, with moderate PTSS and benefit-finding for the parent and peer profiles. Children with cancer demonstrate patterns of connectedness similar to their healthy peers. Findings support connectedness as a possible mechanism facilitating resilience and growth. © The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Relationships between life attitude profile and symptoms experienced with treatment decision evaluation in patients with cancer.

    PubMed

    Erci, Behice; Özdemir, Süreyya

    2013-01-01

    Despite many researches that have examined life attitude profile, treatment decision evaluation, and symptoms experienced in cancer populations, the relationships between life attitude profile and symptoms experienced with treatment decision evaluation are still not well understood. A thorough understanding of these relationships is critical for health care professionals to provide appropriate management to patients. The aim of this study was to determine relationships among life attitude profile, the treatment decision evaluation, and symptoms experienced in Turkish patients with cancer. A convenience sample of 199 patients with cancer at a Turkish university hospital completed a structured questionnaire including demographic characteristics and the Life Attitude Profile-Revised Scale for patients with cancer in 2007. The researchers visited the oncology clinic 5 work days every week and conducted interviews with the patients. The life attitude profile was not correlated with the treatment decision evaluation and symptoms experienced (r = 0.082, r = -026). The treatment decision evaluation showed that the patients were uncertain about their satisfaction with the treatment decision. Significant correlations were found between the treatment decision evaluation and symptoms experienced (r = 0.206; P <.01). Holistic nursing interventions can be implemented as they promote healing of the whole person processes as facilitating self-awareness, living meaningfully, and promotion connection with others and with nature and a higher power.

  14. tRNA modification profiles of the fast-proliferating cancer cells

    SciTech Connect

    Dong, Chao; Niu, Leilei; Song, Wei; Xiong, Xin; Zhang, Xianhua; Zhang, Zhenxi; Yang, Yi; Yi, Fan; Zhan, Jun; Zhang, Hongquan; Yang, Zhenjun; Zhang, Li-He; Zhai, Suodi; Li, Hua; Ye, Min; Du, Quan

    2016-08-05

    Despite the recent progress in RNA modification study, a comprehensive modification profile is still lacking for mammalian cells. Using a quantitative HPLC/MS/MS assay, we present here a study where RNA modifications are examined in term of the major RNA species. With paired slow- and fast-proliferating cell lines, distinct RNA modification profiles are first revealed for diverse RNA species. Compared to mRNAs, increased ribose and nucleobase modifications are shown for the highly-structured tRNAs and rRNAs, lending support to their contribution to the formation of high-order structures. This study also reveals a dynamic tRNA modification profile in the fast-proliferating cells. In addition to cultured cells, this unique tRNA profile has been further confirmed with endometrial cancers and their adjacent normal tissues. Taken together, the results indicate that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. -- Highlights: •RNA modifications were first examined in term of the major RNA species. •A dynamic tRNA modifications was characterized for the fast-proliferating cells. •The unique tRNA profile was confirmed with endometrial cancers and their adjacent normal tissues. •tRNA was predicted as an actively regulated RNA species in the fast-proliferating cancer cells.

  15. Profiles of Connectedness: Processes of Resilience and Growth in Children With Cancer

    PubMed Central

    Howard Sharp, Katianne M.; Willard, Victoria W.; Okado, Yuko; Tillery, Rachel; Barnes, Sarah; Long, Alanna

    2015-01-01

    Objective Identified patterns of connectedness in youth with cancer and demographically similar healthy peers. Method Participants included 153 youth with a history of cancer and 101 youth without a history of serious illness (8–19 years). Children completed measures of connectedness, posttraumatic stress symptoms (PTSS), and benefit-finding. Parents also reported on children’s PTSS. Results Latent profile analysis revealed four profiles: high connectedness (45%), low connectedness (6%), connectedness primarily to parents (40%), and connectedness primarily to peers (9%). These profiles did not differ by history of cancer. However, profiles differed on PTSS and benefit-finding. Children highly connected across domains displayed the lowest PTSS and highest benefit-finding, while those with the lowest connectedness had the highest PTSS, with moderate PTSS and benefit-finding for the parent and peer profiles. Conclusion Children with cancer demonstrate patterns of connectedness similar to their healthy peers. Findings support connectedness as a possible mechanism facilitating resilience and growth. PMID:25968051

  16. Gene expression profiling of non-small cell lung cancer.

    PubMed

    Singhal, Sunil; Miller, Daniel; Ramalingam, Suresh; Sun, Shi-Yong

    2008-06-01

    Functional genomics has emerged over the past 10 years as a novel technology to study genetic alterations. Gene expression arrays are one genomic technique employed to discover changes in the DNA expression that occur in neoplastic transformation. Microarrays have been applied to investigating lung cancer. Specific applications include discovering novel genetic changes that occur in lung tumors. Microarrays can also be applied to improve diagnosis, staging and discover prognostic markers. The eventual goal of this technology is to discover new markers for therapy and to customize therapy based on an individual tumor genetic composition. In this review, we present the current state of gene expression array technology in its application to lung cancer.

  17. Human Gastric Cancer Kinase Profile and Prognostic Significance of MKK4 Kinase

    PubMed Central

    Wu, Chew-Wun; Li, Anna F.-Y.; Chi, Chin-Wen; Huang, Chen Lung; Shen, King-Han; Liu, Wing-Yiu; Lin, Wen-chang

    2000-01-01

    Alterations of protein tyrosine kinase are often associated with uncontrolled cell growth and tumor progression. Knowledge of the overall expression pattern of tyrosine kinases should prove beneficial in understanding the signaling pathways involved in gastric cancer oncogenesis and in providing possible biomarkers for gastric cancer progression. To establish a general tyrosine-kinase expression profile, degenerated polymerase chain reaction primers designed from the consensus catalytic kinase motifs were used to amplify protein tyrosine kinase molecules from gastric cancer tissues. We observed more than 50 tyrosine and serine/threonine kinases from matching pairs of gastric cancer tissue and normal mucosa. Based on this new kinase profile information, we selected the MKK4 gene for further immunohistochemical studies. Statistical analysis of MKK4 protein expression and clinicopathological features indicated that MKK4 kinase expression could serve as a significant prognostic factor for relapse-free survival and for overall survival. We demonstrated a simple and sensitive method for establishing protein tyrosine-kinase expression profiles of human gastric cancer tissues as well as for discovering novel and useful clinical biomarkers from such kinase expression profiles. PMID:10854223

  18. Expression profiles of estrogen-regulated microRNAs in breast cancer cells

    PubMed Central

    Katchy, Anne; Williams, Cecilia

    2016-01-01

    Summary Molecular signaling through both estrogen and microRNAs are critical for breast cancer development and growth. The activity of estrogen is mediated by transcription factors, the estrogen receptors. Here we describe a method for robust characterization of estrogen-regulated microRNA profiles. The method details how to prepare cells for optimal estrogen response, directions for estrogen treatment, RNA extraction, microRNA large-scale profiling and subsequent confirmations. PMID:26585151

  19. Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

    DTIC Science & Technology

    2014-12-01

    false positives rate there is a pressing need to develop reliable molecular biomarkers to supplement the radiologic imaging to improve the sensitivity...of early detection of lung cancer. Based on the notions that: 1) smoking- induced injury alters mRNA and microRNA (miRNA) expression profiles in...signatures and biomarkers derived from the results of aims 1 and 2 to develop and test airway- based biomarkers capable of diagnosing lung cancer in current or

  20. Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans

    DTIC Science & Technology

    2011-10-01

    as DNA sequence changes of any length attributable to insertion or deletion of the microsatellite one- to four-base DNA repeating units within a...capture microdissected material to sequence the transcriptome. This allows us to examine the gene expression profiles in premalignant lesions and...to be the leading cause of cancer- related death in both men and women in the United States. The majority of lung cancers are non-small cell lung

  1. Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans

    DTIC Science & Technology

    2012-10-01

    buccal and nasal cavities 8. Finally, our group has previously shown that gene-expression profiles in cytologically normal mainstem bronchus epithelium...smokers undergoing resection of lung lesions, high-throughput mRNA expression analyses are being performed on cytological specimens (brushings) obtained...Lung cancer. N Engl J Med 359:1367-80, 2008 3. Slaughter D, Southwick H, Smejkal W: Field cancerization in oral stratified squamous epithelium

  2. Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology

    DTIC Science & Technology

    2016-10-01

    Biology PRINCIPAL INVESTIGATOR: Scott A. Tomlins, M.D., Ph.D. CONTRACTING ORGANIZATION: Regents of the University of Michigan Ann Arbor, MI 48109...Cancer to Inform on Prognosis and Disease Biology 5b. GRANT NUMBER W81XWH-15-1-0661 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...169,574/yr Comprehensive Molecular Profiling of African-American Prostate Cancer to Inform on Prognosis and Disease Biology Goal(s): Perform

  3. Bacterial infection profiles in lung cancer patients with febrile neutropenia.

    PubMed

    Lanoix, Jean-Philippe; Pluquet, Emilie; Lescure, Francois Xavier; Bentayeb, Houcine; Lecuyer, Emmanuelle; Boutemy, Marie; Dumont, Patrick; Jounieaux, Vincent; Schmit, Jean Luc; Dayen, Charles; Douadi, Youcef

    2011-06-27

    The chemotherapy used to treat lung cancer causes febrile neutropenia in 10 to 40% of patients. Although most episodes are of undetermined origin, an infectious etiology can be suspected in 30% of cases. In view of the scarcity of data on lung cancer patients with febrile neutropenia, we performed a retrospective study of the microbiological characteristics of cases recorded in three medical centers in the Picardy region of northern France. We analyzed the medical records of lung cancer patients with neutropenia (neutrophil count < 500/mm(3)) and fever (temperature > 38.3°C). The study included 87 lung cancer patients with febrile neutropenia (mean age: 64.2). Two thirds of the patients had metastases and half had poor performance status. Thirty-three of the 87 cases were microbiologically documented. Gram-negative bacteria (mainly enterobacteriaceae from the urinary and digestive tracts) were identified in 59% of these cases. Staphylococcus species (mainly S. aureus) accounted for a high proportion of the identified Gram-positive bacteria. Bacteremia accounted for 60% of the microbiologically documented cases of fever. 23% of the blood cultures were positive. 14% of the infections were probably hospital-acquired and 14% were caused by multidrug-resistant strains. The overall mortality rate at day 30 was 33% and the infection-related mortality rate was 16.1%. Treatment with antibiotics was successful in 82.8% of cases. In a multivariate analysis, predictive factors for treatment failure were age >60 and thrombocytopenia < 20000/mm(3). Gram-negative species were the most frequently identified bacteria in lung cancer patients with febrile neutropenia. Despite the success of antibiotic treatment and a low-risk neutropenic patient group, mortality is high in this particular population.

  4. Individual investigator profiles of biospecimen use in cancer research.

    PubMed

    Braun, Lauren; Lesperance, Maria; Mes-Massons, Anne-Marie; Tsao, Ming S; Watson, Peter H

    2014-06-01

    Establishing targets for case accrual is an important component of a strategic plan for a biobank. We have previously assessed overall patterns of biospecimen use in cancer research publications in selected journals. Here we extend this analysis to consider patterns of biospecimen use in relation to cancer research programs developed by individual investigators. We selected three individual cancer research investigators whose independent research programs began circa 1986, have been characterized by extensive use of human tumor biospecimens, and have primarily involved translational research in the areas of breast, lung, and ovarian cancer. We analyzed biospecimen and data usage in their career publications categorized by numbers, type, and format, and accompanying annotating data in terms of conformance with BRISQ reporting and ethics related criteria. Biospecimens were used in 313/474 (66%) of publications analyzed. The average number of biospecimens used by these research programs increased six-fold from less than 1000 in 2001-2003 to greater than 6000 in 2010-2012, and the average cohort sizes per article also increased from approximately 50 to 200 cases per study over the same period in most biospecimen categories (p<0.05). The relative proportions of different formats of biospecimens used has varied significantly and continues to change with the emergence of digital biospecimen derived data. In these three translational research programs, BRISQ elements relating to 'Biobank' categories were significantly less well reported for biospecimens used in publications than data corresponding to 'Clinical chart' categories (p<0001). This study shows that overall use of biospecimens in cancer research has increased significantly and that dynamic variation in the relative use of different biospecimen formats has also occurred. This study also confirms our previous findings on patterns of biospecimen use and also those concerning incomplete reporting of relevant data

  5. Impact of home enteral nutrition in malnourished patients with upper gastrointestinal cancer: A multicentre randomised clinical trial.

    PubMed

    Gavazzi, Cecilia; Colatruglio, Silvia; Valoriani, Filippo; Mazzaferro, Vincenzo; Sabbatini, Annarita; Biffi, Roberto; Mariani, Luigi; Miceli, Rosalba

    2016-09-01

    Weight loss is frequent in patients with gastrointestinal (GI) cancer. Nutritional status deteriorates throughout anti-cancer treatment, mostly after major surgery, increasing complications, reducing tolerance and worsening the final prognosis. Enteral nutrition is safe and effective in malnourished patients undergoing major GI surgery. Randomised trials aimed at investigating the effects of home enteral nutrition (HEN) in post-surgical patients with GI cancer are lacking. This study compares HEN and counselling in limiting weight loss during oncologic treatment. Patients with upper GI cancer and candidate to major surgery were included in the protocol when the nutritional risk screening (NRS 2002) score was ≥3. All patients were supported with enteral nutrition through a jejunostomy after surgery and randomly assigned to continue enteral nutrition or receiving nutritional counselling after discharge. Nutritional and performance status, quality of life (QoL) and tolerance to cancer treatment have been evaluated at 2 and 6 months after discharge. Seventy-nine patients were randomised; 38 continued enteral nutrition at home and 41 patients received nutritional counselling only. After 2 months, patients on HEN maintained their mean body weight, while patients in the nutritional counselling group showed a weight loss of 3.6 kg. Patients supported on HEN had a higher chance to complete chemotherapy as planned (48% versus 34%). QoL was not worsened by HEN. No complications were reported. HEN is a simple and feasible treatment to support malnourished patients with upper GI cancer after major surgery and during chemotherapy in order to limit further weight loss. Published by Elsevier Ltd.

  6. Use of serum-circulating miRNA profiling for the identification of breast cancer biomarkers.

    PubMed

    Mar-Aguilar, Fermín; Rodríguez-Padilla, Cristina; Reséndez-Pérez, Diana

    2014-01-01

    MicroRNAs (miRNAs) are important regulatory molecules involved in disease pathogenesis. miRNAs are very stable in bodily fluids and can be detected in serum, plasma, saliva, and urine, among other fluids. Several studies have demonstrated the usefulness of serum miRNAs as potential biomarkers for detecting and monitoring cancer progression. Here, we describe in detail the experiment protocol we used to profile miRNA expression in the serum of breast cancer patients, including RNA extraction from serum, RT-qPCR quantification, and analysis of the deregulated miRNAs. Detection of circulating miRNAs may be a useful, noninvasive diagnostic tool for breast cancer.

  7. A Targeted Quantitative Proteomics Strategy for Global Kinome Profiling of Cancer Cells and Tissues*

    PubMed Central

    Xiao, Yongsheng; Guo, Lei; Wang, Yinsheng

    2014-01-01

    Kinases are among the most intensively pursued enzyme superfamilies as targets for anti-cancer drugs. Large data sets on inhibitor potency and selectivity for more than 400 human kinases became available recently, offering the opportunity to design rationally novel kinase-based anti-cancer therapies. However, the expression levels and activities of kinases are highly heterogeneous among different types of cancer and even among different stages of the same cancer. The lack of effective strategy for profiling the global kinome hampers the development of kinase-targeted cancer chemotherapy. Here, we introduced a novel global kinome profiling method, based on our recently developed isotope-coded ATP-affinity probe and a targeted proteomic method using multiple-reaction monitoring (MRM), for assessing simultaneously the expression of more than 300 kinases in human cells and tissues. This MRM-based assay displayed much better sensitivity, reproducibility, and accuracy than the discovery-based shotgun proteomic method. Approximately 250 kinases could be routinely detected in the lysate of a single cell line. Additionally, the incorporation of iRT into MRM kinome library rendered our MRM kinome assay easily transferrable across different instrument platforms and laboratories. We further employed this approach for profiling kinase expression in two melanoma cell lines, which revealed substantial kinome reprogramming during cancer progression and demonstrated an excellent correlation between the anti-proliferative effects of kinase inhibitors and the expression levels of their target kinases. Therefore, this facile and accurate kinome profiling assay, together with the kinome-inhibitor interaction map, could provide invaluable knowledge to predict the effectiveness of kinase inhibitor drugs and offer the opportunity for individualized cancer chemotherapy. PMID:24520089

  8. A targeted quantitative proteomics strategy for global kinome profiling of cancer cells and tissues.

    PubMed

    Xiao, Yongsheng; Guo, Lei; Wang, Yinsheng

    2014-04-01

    Kinases are among the most intensively pursued enzyme superfamilies as targets for anti-cancer drugs. Large data sets on inhibitor potency and selectivity for more than 400 human kinases became available recently, offering the opportunity to design rationally novel kinase-based anti-cancer therapies. However, the expression levels and activities of kinases are highly heterogeneous among different types of cancer and even among different stages of the same cancer. The lack of effective strategy for profiling the global kinome hampers the development of kinase-targeted cancer chemotherapy. Here, we introduced a novel global kinome profiling method, based on our recently developed isotope-coded ATP-affinity probe and a targeted proteomic method using multiple-reaction monitoring (MRM), for assessing simultaneously the expression of more than 300 kinases in human cells and tissues. This MRM-based assay displayed much better sensitivity, reproducibility, and accuracy than the discovery-based shotgun proteomic method. Approximately 250 kinases could be routinely detected in the lysate of a single cell line. Additionally, the incorporation of iRT into MRM kinome library rendered our MRM kinome assay easily transferrable across different instrument platforms and laboratories. We further employed this approach for profiling kinase expression in two melanoma cell lines, which revealed substantial kinome reprogramming during cancer progression and demonstrated an excellent correlation between the anti-proliferative effects of kinase inhibitors and the expression levels of their target kinases. Therefore, this facile and accurate kinome profiling assay, together with the kinome-inhibitor interaction map, could provide invaluable knowledge to predict the effectiveness of kinase inhibitor drugs and offer the opportunity for individualized cancer chemotherapy.

  9. Molecular profiling and commercial predication assays in ovarian cancer: still not ready for prime time?

    PubMed

    Kohn, Elise C

    2014-01-01

    Short of early detection to allow curative primary intervention, the other major barrier to further success in treatment of ovarian cancers is matching the best treatment to the proper ovarian cancer type and to the individual patient. There are several decades of experience applying in vitro chemoresponse testing for solid tumors including ovarian cancer. This concept, first described in 1979, has yet to receive level one evidence supporting its application, despite the testing of numerous assays commercially as well as in academic centers and its use for tens of thousands of patients at a significant cost. The approach-rather than undergoing rigorous scientific examination-is now being muddied by the development of commercial molecular profiling assays from which treatment suggestions are provided. Molecular profiling as a research tool has added value to our understanding and treatment of patients with ovarian cancer. Morphologic and histochemical characterizations coupled now with increasing knowledge of ovarian cancer type-specific molecular patterns is improving our ability to properly diagnosis ovarian cancer type and thus guide therapy. With the exception of the role of germ-line and possibly somatic BRCA1 and BRCA2 mutations and their true predictiveness for probable response to poly(ADP-ribose) polymerase inhibition, molecular typing and profiling has yet to identify druggable molecular targets in ovarian cancer. Its use should be continued as a research and learning tool, and its results should be subjected to clinical trial validation. For very different reasons, neither chemoresponse assays nor molecular profiling are ready for prime time, yet.

  10. Differentiation of cancer cell origin and molecular subtype by plasma membrane N-glycan profiling.

    PubMed

    Hua, Serenus; Saunders, Mary; Dimapasoc, Lauren M; Jeong, Seung Hyup; Kim, Bum Jin; Kim, Suhee; So, Minkyung; Lee, Kwang-Sik; Kim, Jae Han; Lam, Kit S; Lebrilla, Carlito B; An, Hyun Joo

    2014-02-07

    In clinical settings, biopsies are routinely used to determine cancer type and grade based on tumor cell morphology, as determined via histochemical or immunohistochemical staining. Unfortunately, in a significant number of cases, traditional biopsy results are either inconclusive or do not provide full subtype differentiation, possibly leading to inefficient or ineffective treatment. Glycomic profiling of the cell membrane offers an alternate route toward cancer diagnosis. In this study, isomer-sensitive nano-LC/MS was used to directly obtain detailed profiles of the different N-glycan structures present on cancer cell membranes. Membrane N-glycans were extracted from cells representing various subtypes of breast, lung, cervical, ovarian, and lymphatic cancer. Chip-based porous graphitized carbon nano-LC/MS was used to separate, identify, and quantify the native N-glycans. Structure-sensitive N-glycan profiling identified hundreds of glycan peaks per cell line, including multiple isomers for most compositions. Hierarchical clusterings based on Pearson correlation coefficients were used to quickly compare and separate each cell line according to originating organ and disease subtype. Based simply on the relative abundances of broad glycan classes (e.g., high mannose, complex/hybrid fucosylated, complex/hybrid sialylated, etc.), most cell lines were readily differentiated. More closely related cell lines were differentiated based on several-fold differences in the abundances of individual glycans. Based on characteristic N-glycan profiles, primary cancer origins and molecular subtypes could be distinguished. These results demonstrate that stark differences in cancer cell membrane glycosylation can be exploited to create an MS-based biopsy, with potential applications toward cancer diagnosis and direction of treatment.

  11. Expression and Genomic Profiling of Minute Breast Cancer Samples. Addendum

    DTIC Science & Technology

    2007-07-01

    Alteration of gene expression profiles of peripheral mononuclear blood cells by tobacco smoke: implications for periodontal diseases . Oral Microbiol...conventional PCR (reproduced with permission from Nature Publishing Group). Tables I and II: Linkers and primers used in conjunction with NlaIII DNA...burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing

  12. Expression and Genomic Profiling of Minute Breast Cancer Samples

    DTIC Science & Technology

    2006-07-01

    Alteration of gene expression profiles of peripheral mononuclear blood cells by tobacco smoke: implications for periodontal diseases . Oral...conventional PCR (reproduced with permission from Nature Publishing Group). Tables I and II: Linkers and primers used in conjunction with NlaIII DNA...Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions

  13. Metabolomic Profiling of Prostate Cancer Progression During Active Surveillance

    DTIC Science & Technology

    2012-10-01

    that the profile captures the phenotype of Gleason grade 4 we will use clinically significant tumors from men who underwent immediate surgery (i.e. not...matched tumor and benign tissue samples from 5 open prostatectomy (RRP) cases and 5 robotic assisted laparoscopic prostatectomy (RAL) cases (including 3...criteria, collection of sufficient frozen tissue from the prostatectomy, matched to serum and urine collected prior to surgery , and collection of clinical

  14. Gene Expression Profiling of Non-Small Cell Lung Cancer

    PubMed Central

    Miller, Daniel; Ramalingam, Suresh; Sun, Shi-Yong

    2008-01-01

    Functional genomics has emerged over the past ten years as a novel technology to study genetic alterations. Gene expression arrays are one genomic technique employed to discover changes in the DNA expression that occur in neoplastic transformation. Microarrays have been applied to investigating lung cancer. Specific applications include discovering novel genetic changes that occur in lung tumors. Microarrays can also be applied to improve diagnosis, staging, and discover prognostic markers. The eventual goal of this technology is to discover new markers for therapy and to customize therapy based on an individual tumor genetic composition. In this review, we present the current state of gene expression array technology in its application to lung cancer. PMID:18440087

  15. Amino Acid Profiles of Serum and Urine in Search for Prostate Cancer Biomarkers: a Pilot Study.

    PubMed

    Dereziński, Paweł; Klupczynska, Agnieszka; Sawicki, Wojciech; Pałka, Jerzy A; Kokot, Zenon J

    2017-01-01

    There is a great interest in searching for diagnostic biomarkers in prostate cancer patients. The aim of the pilot study was to evaluate free amino acid profiles in their serum and urine. The presented paper shows the first comprehensive analysis of a wide panel of amino acids in two different physiological fluids obtained from the same groups of prostate cancer patients (n = 49) and healthy men (n = 40). The potential of free amino acids, both proteinogenic and non-proteinogenic, as prostate cancer biomarkers and their utility in classification of study participants have been assessed. Several metabolites, which deserve special attention in the further metabolomic investigations on searching for prostate cancer markers, were indicated. Moreover, free amino acid profiles enabled to classify samples to one of the studied groups with high sensitivity and specificity. The presented research provides a strong evidence that ethanolamine, arginine and branched-chain amino acids metabolic pathways can be a valuable source of markers for prostate cancer. The altered concentrations of the above-mentioned metabolites suggest their role in pathogenesis of prostate cancer and they should be further evaluated as clinically useful markers of prostate cancer.

  16. Amino Acid Profiles of Serum and Urine in Search for Prostate Cancer Biomarkers: a Pilot Study

    PubMed Central

    Dereziński, Paweł; Klupczynska, Agnieszka; Sawicki, Wojciech; Pałka, Jerzy A.; Kokot, Zenon J.

    2017-01-01

    There is a great interest in searching for diagnostic biomarkers in prostate cancer patients. The aim of the pilot study was to evaluate free amino acid profiles in their serum and urine. The presented paper shows the first comprehensive analysis of a wide panel of amino acids in two different physiological fluids obtained from the same groups of prostate cancer patients (n = 49) and healthy men (n = 40). The potential of free amino acids, both proteinogenic and non-proteinogenic, as prostate cancer biomarkers and their utility in classification of study participants have been assessed. Several metabolites, which deserve special attention in the further metabolomic investigations on searching for prostate cancer markers, were indicated. Moreover, free amino acid profiles enabled to classify samples to one of the studied groups with high sensitivity and specificity. The presented research provides a strong evidence that ethanolamine, arginine and branched-chain amino acids metabolic pathways can be a valuable source of markers for prostate cancer. The altered concentrations of the above-mentioned metabolites suggest their role in pathogenesis of prostate cancer and they should be further evaluated as clinically useful markers of prostate cancer. PMID:28138303

  17. Stromal proteome expression profile and muscle-invasive bladder cancer research

    PubMed Central

    2012-01-01

    Background To globally characterize the cancer stroma expression profile of muscle-invasive transitional cell carcinoma and to discuss the cancer biology as well as biomarker discovery from stroma. Laser capture micro dissection was used to harvest purified muscle-invasive bladder cancer stromal cells and normal urothelial stromal cells from 4 paired samples. Two-dimensional liquid chromatography tandem mass spectrometry was used to identify the proteome expression profile. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature. Results We identified 868/872 commonly expressed proteins and 978 differential proteins from 4 paired cancer and normal stromal samples using laser capture micro dissection coupled with two-dimensional liquid chromatography tandem mass spectrometry. 487/491 proteins uniquely expressed in cancer/normal stroma. Differential proteins were compared with the entire list of the international protein index (IPI), and there were 42/42 gene ontology (GO) terms exhibited as enriched and 8/5 exhibited as depleted in cellular Component, respectively. Significantly altered pathways between cancer/normal stroma mainly include metabolic pathways, ribosome, focal adhesion, etc. Finally, descriptive statistics show that the stromal proteins with extremes of PI and MW have the same probability to be a biomarker. Conclusions Based on our results, stromal cells are essential component of the cancer, biomarker discovery and network based multi target therapy should consider neoplastic cells itself and corresponding stroma as whole one. PMID:22920603

  18. Abnormalities in plasma and red blood cell fatty acid profiles of patients with colorectal cancer.

    PubMed Central

    Baró, L.; Hermoso, J. C.; Núñez, M. C.; Jiménez-Rios, J. A.; Gil, A.

    1998-01-01

    We evaluated total plasma fatty acid concentrations and percentages, and the fatty acid profiles for the different plasma lipid fractions and red blood cell lipids, in 17 patients with untreated colorectal cancer and 12 age-matched controls with no malignant diseases, from the same geographical area. Cancer patients had significantly lower total plasma concentrations of saturated, monounsaturated and essential fatty acids and their polyunsaturated derivatives than healthy controls; when the values were expressed as relative percentages, cancer patients had significantly higher proportions of oleic acid and lower levels of linoleic acid than controls. With regard to lipid fractions, cancer patients had higher proportions of oleic acid in plasma phospholipids, triglycerides and cholesterol esters, and lower percentages of linoleic acid and its derivatives. On the other hand, alpha-linolenic acid was significantly lower in triglycerides from cancer patients and tended to be lower in phospholipids. Its derivatives also tended to be lower in phospholipids and triglycerides from cancer patients. Our findings suggest that colorectal cancer patients present abnormalities in plasma and red blood cell fatty acid profiles characterized by lower amounts of most saturated, monounsaturated and essential fatty acids and their polyunsaturated derivatives, especially members of the n-6 series, than their healthy age-matched counterparts. These changes are probably due to metabolic changes caused by the illness per se but not to malnutrition. PMID:9667678

  19. Obesity and menopause modify the epigenomic profile of breast cancer.

    PubMed

    Crujeiras, Ana B; Diaz-Lagares, Angel; Stefansson, Olafur A; Macias-Gonzalez, Manuel; Sandoval, Juan; Cueva, Juan; Lopez-Lopez, Rafael; Moran, Sebastian; Jonasson, Jon G; Tryggvadottir, Laufey; Olafsdottir, Elinborg; Tinahones, Francisco J; Carreira, Marcos C; Casanueva, Felipe F; Esteller, Manel

    2017-07-01

    Obesity is a high risk factor for breast cancer. This relationship could be marked by a specific methylome. The current work was aimed to explore the impact of obesity and menopausal status on variation in breast cancer methylomes. Data from Infinium 450K array-based methylomes of 64 breast tumors were coupled with information on BMI and menopausal status. Additionally, DNA methylation results were validated in 18 non-tumor and 81 tumor breast samples. Breast tumors arising in either pre- or postmenopausal women stratified by BMI or menopausal status alone were not associated with a specific DNA methylation pattern. Intriguingly, the DNA methylation pattern identified in association with the high-risk group (postmenopausal women with high BMI (>25) and premenopausal women with normal or low BMI < 25) exclusively characterized by hypermethylation of 1287 CpG sites as compared with the low-risk group. These CpG sites included the promoter region of fourteen protein-coding genes of which CpG methylation over the ZNF577 promoter region represents the top scoring associated event. In an independent cohort, the ZNF577 promoter methylation remained statistically significant in association with the high-risk group. Additionally, the impact of ZNF577 promoter methylation on mRNA expression levels was demonstrated in breast cancer cell lines after treatment with a demethylating agent (5-azacytidine). In conclusion, the epigenome of breast tumors is affected by a complex interaction between BMI and menopausal status. The ZNF577 methylation quantification is clearly relevant for the development of novel biomarkers of precision therapy in breast cancer. © 2017 Society for Endocrinology.

  20. Audiological profile of patients treated for childhood cancer.

    PubMed

    Liberman, Patricia Helena Pecora; Goffi-Gomez, Maria Valéria Schmidt; Schultz, Christiane; Novaes, Paulo Eduardo; Lopes, Luiz Fernando

    To characterize the hearing loss after cancer treatment, according to the type of treatment, with identification of predictive factors. Two hundred patients who had cancer in childhood were prospectively evaluated. The mean age at diagnosis was 6 years, and at the audiometric assessment, 21 years. The treatment of the participants included chemotherapy without using platinum derivatives or head and neck radiotherapy in 51 patients; chemotherapy using cisplatin without radiotherapy in 64 patients; head and neck radiotherapy without cisplatin in 75 patients; and a combined treatment of head and neck radiotherapy and chemotherapy with cisplatin in ten patients. Patients underwent audiological assessment, including pure tone audiometry, speech audiometry, and immittancemetry. The treatment involving chemotherapy with cisplatin caused 41.9% and 47.3% hearing loss in the right and left ear, respectively, with a 11.7-fold higher risk of hearing loss in the right ear and 17.6-fold higher in the left ear versus patients not treated with cisplatin (p<0.001 and p<0.001, respectively). Children whose cancer diagnosis occurred after the age of 6 have shown an increased risk of hearing loss vs. children whose diagnosis occurred under 6 years of age (p=0.02). The auditory feature found after the cancer treatment was a symmetrical bilateral sensorineural hearing loss. Chemotherapy with cisplatin proved to be a risk factor, while head and neck radiotherapy was not critical for the occurrence of hearing loss. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  1. Comprehensive genomic profiles of small cell lung cancer

    PubMed Central

    George, Julie; Lim, Jing Shan; Jang, Se Jin; Cun, Yupeng; Ozretić, Luka; Kong, Gu; Leenders, Frauke; Lu, Xin; Fernández-Cuesta, Lynnette; Bosco, Graziella; Müller, Christian; Dahmen, Ilona; Jahchan, Nadine S.; Park, Kwon-Sik; Yang, Dian; Karnezis, Anthony N.; Vaka, Dedeepya; Torres, Angela; Wang, Maia Segura; Korbel, Jan O.; Menon, Roopika; Chun, Sung-Min; Kim, Deokhoon; Wilkerson, Matt; Hayes, Neil; Engelmann, David; Pützer, Brigitte; Bos, Marc; Michels, Sebastian; Vlasic, Ignacija; Seidel, Danila; Pinther, Berit; Schaub, Philipp; Becker, Christian; Altmüller, Janine; Yokota, Jun; Kohno, Takashi; Iwakawa, Reika; Tsuta, Koji; Noguchi, Masayuki; Muley, Thomas; Hoffmann, Hans; Schnabel, Philipp A.; Petersen, Iver; Chen, Yuan; Soltermann, Alex; Tischler, Verena; Choi, Chang-min; Kim, Yong-Hee; Massion, Pierre P.; Zou, Yong; Jovanovic, Dragana; Kontic, Milica; Wright, Gavin M.; Russell, Prudence A.; Solomon, Benjamin; Koch, Ina; Lindner, Michael; Muscarella, Lucia A.; la Torre, Annamaria; Field, John K.; Jakopovic, Marko; Knezevic, Jelena; Castaños-Vélez, Esmeralda; Roz, Luca; Pastorino, Ugo; Brustugun, Odd-Terje; Lund-Iversen, Marius; Thunnissen, Erik; Köhler, Jens; Schuler, Martin; Botling, Johan; Sandelin, Martin; Sanchez-Cespedes, Montserrat; Salvesen, Helga B.; Achter, Viktor; Lang, Ulrich; Bogus, Magdalena; Schneider, Peter M.; Zander, Thomas; Ansén, Sascha; Hallek, Michael; Wolf, Jürgen; Vingron, Martin; Yatabe, Yasushi; Travis, William D.; Nürnberg, Peter; Reinhardt, Christian; Perner, Sven; Heukamp, Lukas; Büttner, Reinhard; Haas, Stefan A.; Brambilla, Elisabeth; Peifer, Martin; Sage, Julien; Thomas, Roman K.

    2016-01-01

    We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer. PMID:26168399

  2. Monitoring the profile of cervical cancer in a developing city

    PubMed Central

    2013-01-01

    Background Medical records are frequently consulted to verify whether the treatment and guiding principles were correct. Determine incidence and mortality trends of in situ and invasive neoplasms of the uterine cervix, in the period 1988–2004 in Goiânia, Brazil. Methods The incident cases were identified through the Population-Based Cancer Registry of Goiânia. Population data were collected from census data of the Brazilian Institute of Geography and Statistics. For mortality analysis, data were extracted from the Mortality Information System. The Poisson Regression was utilized to determine the annual incidence and mortality rates. Results A total of 4446 cases of in situ and invasive neoplasms of the uterine cervix were identified. No significant reductions were verified in invasive cervical cancer rates (p = 0.386) during the study period, while in situ carcinomas presented an annual increasing trend of 13.08% (p < 0.001). A decreasing trend was observed for mortality (3.02%, p = 0.017). Conclusion No reduction was observed for the incidence of invasive cancer of the uterine cervix; however, increasing trends were verified for in situ lesions with a consequent reduction in mortality rates. These increasing trends may be the result of recently-implemented screening programs or due to improvements in the notification system. PMID:23759074

  3. Cohort profile: the Social Inequality in Cancer (SIC) cohort study.

    PubMed

    Nordahl, Helene; Hvidtfeldt, Ulla Arthur; Diderichsen, Finn; Rod, Naja Hulvej; Osler, Merete; Frederiksen, Birgitte Lidegaard; Prescott, Eva; Tjønneland, Anne; Lange, Theis; Keiding, Niels; Andersen, Per Kragh; Andersen, Ingelise

    2014-12-01

    The Social Inequality in Cancer (SIC) cohort study was established to determine pathways through which socioeconomic position affects morbidity and mortality, in particular common subtypes of cancer. Data from seven well-established cohort studies from Denmark were pooled. Combining these cohorts provided a unique opportunity to generate a large study population with long follow-up and sufficient statistical power to develop and apply new methods for quantification of the two basic mechanisms underlying social inequalities in cancer-mediation and interaction. The SIC cohort included 83 006 participants aged 20-98 years at baseline. A wide range of behavioural and biological risk factors such as smoking, physical inactivity, alcohol intake, hormone replacement therapy, body mass index, blood pressure and serum cholesterol were assessed by self-administered questionnaires, physical examinations and blood samples. All participants were followed up in nationwide demographic and healthcare registries. For those interested in collaboration, further details can be obtained by contacting the Steering Committee at the Department of Public Health, University of Copenhagen, at inan@sund.ku.dk.

  4. Bioactive food components and cancer-specific metabonomic profiles.

    PubMed

    Kim, Young S; Milner, John A

    2011-01-01

    Cancer cells possess unique metabolic signatures compared to normal cells, including shifts in aerobic glycolysis, glutaminolysis, and de novo biosynthesis of macromolecules. Targeting these changes with agents (drugs and dietary components) has been employed as strategies to reduce the complications associated with tumorigenesis. This paper highlights the ability of several food components to suppress tumor-specific metabolic pathways, including increased expression of glucose transporters, oncogenic tyrosine kinase, tumor-specific M2-type pyruvate kinase, and fatty acid synthase, and the detection of such effects using various metabonomic technologies, including liquid chromatography/mass spectrometry (LC/MS) and stable isotope-labeled MS. Stable isotope-mediated tracing technologies offer exciting opportunities for defining specific target(s) for food components. Exposures, especially during the early transition phase from normal to cancer, are critical for the translation of knowledge about food components into effective prevention strategies. Although appropriate dietary exposures needed to alter cellular metabolism remain inconsistent and/or ill-defined, validated metabonomic biomarkers for dietary components hold promise for establishing effective strategies for cancer prevention.

  5. A Clinicopathological Profile of Prostate Cancer in Trinidad and Tobago

    PubMed Central

    Sukhraj, Rajendra; Goetz, Lester

    2016-01-01

    Aim. To conduct a clinicopathological review of all prostate biopsies performed in a tertiary referral centre in Trinidad and Tobago over a period of 30 months. Methods. The records of all patients who had prostate biopsies from January 2012 to July 2014 were reviewed. Clinical and pathologic data were compiled and subsequently analysed using SPSS version 20. Results. From January 2012 to July 2014, 617 transrectal ultrasound guided prostate biopsies were performed. Pathological data were found for 546 patients of whom 283 (51.8%) were confirmed carcinoma of the prostate. Moderately differentiated tumors (Gleason 7) were the most common group. Using the D'Amico risk classification, most cases were found to be high risk (63.1%). Afro-Trinidadians comprised 72.1% of the patients with prostate cancer. Afro-Trinidadians were also more likely to have high risk and high grade disease as well as high PSA values. Conclusion. This study demonstrates that over half of our biopsies are eventually positive for cancer and most cases were high risk. Afro-Trinidadians comprised a disproportionate number of those diagnosed with prostate cancer and had a greater risk of high risk disease. PMID:27493662

  6. Comprehensive genomic profiles of small cell lung cancer.

    PubMed

    George, Julie; Lim, Jing Shan; Jang, Se Jin; Cun, Yupeng; Ozretić, Luka; Kong, Gu; Leenders, Frauke; Lu, Xin; Fernández-Cuesta, Lynnette; Bosco, Graziella; Müller, Christian; Dahmen, Ilona; Jahchan, Nadine S; Park, Kwon-Sik; Yang, Dian; Karnezis, Anthony N; Vaka, Dedeepya; Torres, Angela; Wang, Maia Segura; Korbel, Jan O; Menon, Roopika; Chun, Sung-Min; Kim, Deokhoon; Wilkerson, Matt; Hayes, Neil; Engelmann, David; Pützer, Brigitte; Bos, Marc; Michels, Sebastian; Vlasic, Ignacija; Seidel, Danila; Pinther, Berit; Schaub, Philipp; Becker, Christian; Altmüller, Janine; Yokota, Jun; Kohno, Takashi; Iwakawa, Reika; Tsuta, Koji; Noguchi, Masayuki; Muley, Thomas; Hoffmann, Hans; Schnabel, Philipp A; Petersen, Iver; Chen, Yuan; Soltermann, Alex; Tischler, Verena; Choi, Chang-min; Kim, Yong-Hee; Massion, Pierre P; Zou, Yong; Jovanovic, Dragana; Kontic, Milica; Wright, Gavin M; Russell, Prudence A; Solomon, Benjamin; Koch, Ina; Lindner, Michael; Muscarella, Lucia A; la Torre, Annamaria; Field, John K; Jakopovic, Marko; Knezevic, Jelena; Castaños-Vélez, Esmeralda; Roz, Luca; Pastorino, Ugo; Brustugun, Odd-Terje; Lund-Iversen, Marius; Thunnissen, Erik; Köhler, Jens; Schuler, Martin; Botling, Johan; Sandelin, Martin; Sanchez-Cespedes, Montserrat; Salvesen, Helga B; Achter, Viktor; Lang, Ulrich; Bogus, Magdalena; Schneider, Peter M; Zander, Thomas; Ansén, Sascha; Hallek, Michael; Wolf, Jürgen; Vingron, Martin; Yatabe, Yasushi; Travis, William D; Nürnberg, Peter; Reinhardt, Christian; Perner, Sven; Heukamp, Lukas; Büttner, Reinhard; Haas, Stefan A; Brambilla, Elisabeth; Peifer, Martin; Sage, Julien; Thomas, Roman K

    2015-08-06

    We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.

  7. Metabolomic Profiling of Hormone-Dependent Cancers: A Bird’s Eye View

    PubMed Central

    Lloyd, Stacy M.; Arnold, James; Sreekumar, Arun

    2015-01-01

    Hormone-dependent cancers present a significant public health challenge, as they are among the most common cancers in the world. One factor associated with cancer development and progression is metabolic reprogramming. By understanding these alterations, we can identify potential markers and novel biochemical therapeutic targets. Metabolic profiling is an advanced technology that allows investigators to assess low molecular weight compounds that reflect physiological alterations. Current research in metabolomics in prostate and breast cancer has made great strides in uncovering specific metabolic pathways that are associated with cancer development, progression, and resistance. This review will highlight some of the major findings and potential therapeutic advances that have been reported utilizing this technology. PMID:26242817

  8. Profiles.

    ERIC Educational Resources Information Center

    Macintosh, Henry G.

    An introduction to profiles is presented with examples provided to permit an overall appraisal of the potential of profiles, of the principles upon which they might be based, and of the problems that will have to be overcome if their potential is to be realized in practice. The larger scale examples of profiles discussed are the Scottish Pupil…

  9. Methylation profiling of 48 candidate genes in tumor and matched normal tissues from breast cancer patients.

    PubMed

    Li, Zibo; Guo, Xinwu; Wu, Yepeng; Li, Shengyun; Yan, Jinhua; Peng, Limin; Xiao, Zhi; Wang, Shouman; Deng, Zhongping; Dai, Lizhong; Yi, Wenjun; Xia, Kun; Tang, Lili; Wang, Jun

    2015-02-01

    Gene-specific methylation alterations in breast cancer have been suggested to occur early in tumorigenesis and have the potential to be used for early detection and prevention. The continuous increase in worldwide breast cancer incidences emphasizes the urgent need for identification of methylation biomarkers for early cancer detection and patient stratification. Using microfluidic PCR-based target enrichment and next-generation bisulfite sequencing technology, we analyzed methylation status of 48 candidate genes in paired tumor and normal tissues from 180 Chinese breast cancer patients. Analysis of the sequencing results showed 37 genes differentially methylated between tumor and matched normal tissues. Breast cancer samples with different clinicopathologic characteristics demonstrated distinct profiles of gene methylation. The methylation levels were significantly different between breast cancer subtypes, with basal-like and luminal B tumors having the lowest and the highest methylation levels, respectively. Six genes (ACADL, ADAMTSL1, CAV1, NPY, PTGS2, and RUNX3) showed significant differential methylation among the 4 breast cancer subtypes and also between the ER +/ER- tumors. Using unsupervised hierarchical clustering analysis, we identified a panel of 13 hypermethylated genes as candidate biomarkers that performed a high level of efficiency for cancer prediction. These 13 genes included CST6, DBC1, EGFR, GREM1, GSTP1, IGFBP3, PDGFRB, PPM1E, SFRP1, SFRP2, SOX17, TNFRSF10D, and WRN. Our results provide evidence that well-defined DNA methylation profiles enable breast cancer prediction and patient stratification. The novel gene panel might be a valuable biomarker for early detection of breast cancer.

  10. Comparison of protein expression profiles of different stages of lymph nodes metastasis in breast cancer.

    PubMed

    Lee, Hui-Hua; Lim, Chu-Ai; Cheong, Yew-Teik; Singh, Manjit; Gam, Lay-Harn

    2012-01-01

    Breast cancer is the most common cancer among women worldwide. Breast cancer metastasis primarily happens through lymphatic system, where the extent of lymph node metastasis is the major factor influencing staging, prognosis and therapeutic decision of the disease. We aimed to study the protein expression changes in different N (regional lymph nodes) stages of breast cancer. Protein expression profiles of breast cancerous and adjacent normal tissues were mapped by proteomics approach that comprises of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and tandem mass spectrometry (LC-MS/MS) analysis. Calreticulin and tropomyosin alpha 3 chains were the common up-regulated proteins in N0, N1 and N2 stages of breast cancer. Potential biomarker for each N stage was HSP 70 for N0, 80 k protein H precursor and PDI for N1 stage while 78 kDa glucose-regulated protein was found useful for N2 stage. In addition, significant up-regulation of PDI A3 was detected only in the metastasized breast cancer. The up-regulation expression of these proteins in cancerous tissues can potentially use as indicators for diagnosis, treatment and prognosis of different N stages of breast cancer.

  11. MiRNA molecular profiles in human medical conditions: connecting lung cancer and lung development phenomena.

    PubMed

    Aghanoori, Mohamad-Reza; Mirzaei, Behnaz; Tavallaei, Mahmood

    2014-01-01

    MiRNAs are endogenous, single stranded ~22-nucleotide non-coding RNAs (ncRNAs) which are transcribed by RNA polymerase II and mediate negative post-transcriptional gene regulation through binding to 3'untranslated regions (UTR), possibly open reading frames (ORFs) or 5'UTRs of target mRNAs. MiRNAs are involved in the normal physiology of eukaryotic cells, so dysregulation may be associated with diseases like cancer, and neurodegenerative, heart and other disorders. Among all cancers, lung cancer, with high incidence and mortality worldwide, is classified into two main groups: non-small cell lung cancer and small cell lung cancer. Recent promising studies suggest that gene expression profiles and miRNA signatures could be a useful step in a noninvasive, low-cost and repeatable screening process of lung cancer. Similarly, every stage of lung development during fetal life is associated with specific miRNAs. Since lung development and lung cancer phenomena share the same physiological, biological and molecular processes like cell proliferation, development and shared mRNA or expression regulation pathways, and according to data adopted from various studies, they may have partially shared miRNA signature. Thus, focusing on lung cancer in relation to lung development in miRNA studies might provide clues for lung cancer diagnosis and prognosis.

  12. Discovery of molecular associations among aging, stem cells, and cancer based on gene expression profiling.

    PubMed

    Wang, Xiaosheng

    2013-04-01

    The emergence of a huge volume of "omics" data enables a computational approach to the investigation of the biology of cancer. The cancer informatics approach is a useful supplement to the traditional experimental approach. I reviewed several reports that used a bioinformatics approach to analyze the associations among aging, stem cells, and cancer by microarray gene expression profiling. The high expression of aging- or human embryonic stem cell-related molecules in cancer suggests that certain important mechanisms are commonly underlying aging, stem cells, and cancer. These mechanisms are involved in cell cycle regulation, metabolic process, DNA damage response, apoptosis, p53 signaling pathway, immune/inflammatory response, and other processes, suggesting that cancer is a developmental and evolutional disease that is strongly related to aging. Moreover, these mechanisms demonstrate that the initiation, proliferation, and metastasis of cancer are associated with the deregulation of stem cells. These findings provide insights into the biology of cancer. Certainly, the findings that are obtained by the informatics approach should be justified by experimental validation. This review also noted that next-generation sequencing data provide enriched sources for cancer informatics study.

  13. A classification system for clinical relevance of somatic variants identified in molecular profiling of cancer.

    PubMed

    Sukhai, Mahadeo A; Craddock, Kenneth J; Thomas, Mariam; Hansen, Aaron R; Zhang, Tong; Siu, Lillian; Bedard, Philippe; Stockley, Tracy L; Kamel-Reid, Suzanne

    2016-02-01

    Interpretation systems for clinical laboratory reporting of genetic variants for inherited conditions have been widely published. By contrast, there are no existing systems for interpretation and classification of somatic variants found from molecular testing of cancer. We designed an assessment protocol and classification system for somatic variants identified through next-generation sequencing molecular profiling of tumor-derived samples and applied these to a pilot dataset of somatic variants found by next-generation sequencing profiling of 158 tumor samples derived from advanced cancer patients examined at the Princess Margaret Cancer Centre. We present a classification system to interpret the significance of genetic variants in molecular analysis of cancer, including the following key factors: (i) known or predicted pathogenicity of the variant; (ii) primary site and tumor histology in which the variant is found; (iii) recurrence of the variant; and (iv) evidence of clinical actionability. We used these factors to develop a five-category somatic variant classification for simplified reporting of variant interpretations to treating oncologists. Our somatic variant classification can be of practical value to other clinical molecular laboratories performing cancer genetic profiling by promoting consistent reporting of somatic variants and permitting harmonization of variant data among laboratories and clinical studies.

  14. Rapid detection and profiling of rare cancer cells with a portable holographic imaging system

    NASA Astrophysics Data System (ADS)

    Im, Hyungsoon; Song, Jun; Liong, Monty; Fexon, Lioubov; Pivovarov, Misha; Weissleder, Ralph; Lee, Hakho

    2013-03-01

    We herein present the detection and molecular profiling of rare cancer cells, using a chip-based holographic imaging system. In this approach, target cancer cells are labeled with molecular-specific microbeads. Such labeling enables 1) a reliable differentiation between cancer cells and host cells (e.g., leukocytes); and 2) quantitative profiling of target marker expression through bead-counting. A new algorithm for digital image reconstruction and bead counting was developed as well to facilitate the assay. The developed system were able to accurately count more than thousands of beads and cells in a single image. Importantly, the assay could be performed without any dilution or washing steps, minimizing cell loss and simplifying the assay procedure. By counting the number of beads attached on cells, we could also measure the expression levels of different cancer markers, which showed good agreement with profiling results by flow cytometry and fluorescence microscopy. This cost-effective, portable, flow-based holographic imaging system is applicable to detecting rare cancer cells in a large volume of blood samples for point-of-care applications.

  15. LC-MS-based serum metabolic profiling for genitourinary cancer classification and cancer type-specific biomarker discovery.

    PubMed

    Lin, Lin; Huang, Zhenzhen; Gao, Yao; Chen, Yongjing; Hang, Wei; Xing, Jinchun; Yan, Xiaomei

    2012-08-01

    Bladder cancer (BC) and kidney cancer (KC) are the first two commonly occurring genitourinary cancers in China. In this study, a comprehensive LC-MS-based method, which utilizes both reversed phase liquid chromatography (RPLC) and hydrophilic interaction chromatography (HILIC) separations, has been carried out in conjunction with multivariate data analysis to discriminate the global serum profiles of BC, KC, and noncancer controls. An independent test set consisting of different patients has been used to objectively evaluate the predictive ability of the analysis platform. Excellent sensitivity and specificity have been achieved in detection of KC and BC. The results suggest that serum metabolic profiling could be used for different types of genitourinary cancer diagnosis. Furthermore, cancer type-specific biomarkers were found through a critical selection criterion. As a result, eicosatrienol, azaprostanoic acid, docosatrienol, retinol, and 14'-apo-beta-carotenal  were found as specific biomarkers for BC; and PE(P-16:0e/0:0), glycerophosphorylcholine, ganglioside GM3 (d18:1/22:1), C17 sphinganine, and SM(d18:0/16:1(9Z)) were found as specific biomarkers for KC. Receiver operating characteristic (ROC) analysis was used for the preliminary evaluation of the biomarkers. These biomarkers have great potential to be used in the clinical diagnosis after further rigorous assessment.

  16. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

    PubMed Central

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

    2016-01-01

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

  17. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

    PubMed

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

    2016-02-29

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

  18. Barriers preventing the adoption of comprehensive cancer genomic profiling in the clinic.

    PubMed

    Statz, Cara M; Patterson, Sara E; Mockus, Susan M

    2017-06-01

    Comprehensive cancer genomic profiling provides the opportunity to expose the various molecular aberrations potentially driving tumor progression. Consequently, the identity of these genetic drivers can be utilized to match a patient to the most appropriate targeted therapy, thereby increasing the probability of improved clinical outcome. Despite its capability of informing patient care, the adoption of comprehensive cancer genomic profiling in the clinic has not been widespread. The barriers surrounding its universal acceptance are attributed to both physician and patient perspectives. Areas covered: The following report discusses the various obstacles in place, including those related to clinical utility, education, insurance coverage, and clinical trials, which can deter physicians and patients from utilizing genomic profiling for therapeutic decision-making. Expert commentary: The authors review the recent growth and potential of clinical utility studies over the last two years, provide a suggestive framework for educational support, and comment on the use of social media to enhance clinical trial recruitment.

  19. Rapid detection and profiling of cancer cells in fine-needle aspirates

    PubMed Central

    Lee, Hakho; Yoon, Tae-Jong; Figueiredo, Jose-Luiz; Swirski, Filip K.; Weissleder, Ralph

    2009-01-01

    There is a growing need for fast, highly sensitive and quantitative technologies to detect and profile unaltered cells in biological samples. Technologies in current clinical use are often time consuming, expensive, or require considerable sample sizes. Here, we report a diagnostic magnetic resonance (DMR) sensor that combines a miniaturized NMR probe with targeted magnetic nanoparticles for detection and molecular profiling of cancer cells. The sensor measures the transverse relaxation rate of water molecules in biological samples in which target cells of interest are labeled with magnetic nanoparticles. We achieved remarkable sensitivity improvements over our prior DMR prototypes by synthesizing new nanoparticles with higher transverse relaxivity and by optimizing assay protocols. We detected as few as 2 cancer cells in 1-μL sample volumes of unprocessed fine-needle aspirates of tumors and profiled the expression of several cellular markers in <15 min. PMID:19620715

  20. Serum cytokine profile in patients with pancreatic cancer.

    PubMed

    Torres, Carolina; Perales, Sonia; Alejandre, María José; Iglesias, José; Palomino, Rogelio J; Martin, Miguel; Caba, Octavio; Prados, José C; Aránega, Antonia; Delgado, Juan R; Irigoyen, Antonio; Ortuño, Francisco M; Rojas, Ignacio; Linares, Ana

    2014-10-01

    Pancreatic ductal adenocarcinoma is a deadly disease because of late diagnosis and chemoresistance. We aimed to find a panel of serum cytokines representing diagnostic and predictive biomarkers for pancreatic cancer. A cytokine antibody array was performed to simultaneously identify 507 cytokines in sera of patients with pancreatic cancer and healthy controls. The nonparametric Mann-Whitney U test was used to pairwise compare the controls, the pretreated patients, and the posttreated patients. Fold changes greater than or equal to 1.5 or less than or equal to 1/1.5 were considered significant. Receiver operating characteristic curves were used to assess the performance of the model. A leave-one-out cross-validation was used for estimating prediction error. Comparing the sera of pretreated patients against the control samples, the cytokines fibroblast growth factor 10 (FGF-10/keratinocyte growth factor-2 (KGF-2), chemokine (C-X-C motif) ligand 11 interferon inducible T cell alpha chemokine (I-TAC)/chemokine [C-X-C motif] ligand 11 (CXCL11), oncostatin M (OSM), osteoactivin/glycoprotein nonmetastatic melanoma protein B, and stem cell factor (SCF) were found significantly overexpressed. Besides, the cytokines CD30 ligand/tumor necrosis factor superfamily, member 8 (TNFSF8), chordin-like 2, FGF-10/KGF-2, growth/differentiation factor 15, I-TAC/CXCL11, OSM, and SCF were differentially expressed in response to treatment. We propose a role for FGF-10/KGF-2, I-TAC/CXCL11, OSM, osteoactivin/glycoprotein nonmetastatic melanoma protein B, and SCF as novel diagnostic biomarkers. CD30 ligand/TNFSF8, chordin-like 2, FGF-10/KGF-2, growth/differentiation factor 15, I-TAC/CXCL11, OSM, and SCF might represent as predictive biomarkers for gemcitabine and erlotinib response of patients with pancreatic cancer.

  1. Methylation profiles of endometrioid and serous endometrial cancers.

    PubMed

    Seeber, Laura M S; Zweemer, Ronald P; Marchionni, Luigi; Massuger, Leon F A G; Smit, Vincent T H B M; van Baal, W Marchien; Verheijen, René H M; van Diest, Paul J

    2010-09-01

    Promoter methylation is a gene- and cancer type-specific epigenetic event that plays an important role in tumour development. As endometrioid (endometrioid endometrial carcinoma, EEC) and serous endometrial cancers (uterine papillary serous carcinoma, UPSC) exhibit different clinical, histological and molecular genetic characteristics, we hypothesized that these differences may be reflected in epigenetic phenomena as well. Identification of a panel of methylation biomarkers could be helpful in a correct histological classification of these two subtypes, which solely on the basis of morphology is not always easy. Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of different tumour suppressor genes in EEC and UPSC. Methylation results were correlated with histology and survival. The median cumulative methylation index of all genes was significantly higher in EEC (124) than in UPSC (93) (P<0.001). Promoter methylation of CDH13 and MLH1 was more frequently present in EEC, while CDKN2B and TP73 were more frequently methylated in UPSC. Almost 90% of EEC and 70% of UPSC could be predicted by CDH13 and TP73. In EEC, methylation of MLH1 was associated with a shorter disease-free survival (DFS; P<0.0001) and overall survival (OS; P=0.005). In a multivariate model, MLH1 methylation emerged as an additional prognostic factor to stage for DFS (P=0.002). In conclusion, promoter methylation is more common in EEC than UPSC. A panel of methylation biomarkers could be useful to distinguish between the two histological subtypes of endometrial cancer. Furthermore, methylation of MLH1 may have prognostic value in EEC.

  2. Gene profiling suggests a common evolution of bladder cancer subtypes

    PubMed Central

    2013-01-01

    Background Bladder cancer exists as several distinct subtypes, including urothelial carcinoma (UCa), squamous cell carcinoma (SCCa), adenocarcinoma and small cell carcinoma. These entities, despite showing distinct morphology and clinical behavior, arise from the urothelial lining and are often accompanied by similar precursor/in situ findings. The relationship between these subtypes has not been explored in detail. Methods We compared gene expression analysis of the two most common subtypes of bladder cancer, UCa (n = 10) and SCCa (n = 9), with an additional comparison to normal urothelium from non-cancer patients (n = 8) using Affymetrix GeneChip Human genome arrays (Affymetrix, Santa Clara, CA). The results were stratified by supervised and unsupervised clustering analysis, as well as by overall fold change in gene expression. Results When compared to normal urothelium, UCa showed differential expression of 155 genes using a 5-fold cut-off. Examples of differentially regulated genes included topoisomerases, cancer-related transcription factors and cell cycle mediators. A second comparison of normal urothelium to SCCa showed differential expression of 503 genes, many of which were related to squamous-specific morphology (desmosomal complex, intermediate filaments present within squamous epithelium, squamous cornifying proteins, and molecules upregulated in squamous carcinomas from other anatomic sites). When compared, 137 genes were commonly dysregulated in both UCa and SCCa as compared to normal urothelium. All dysregulated genes in UCa were shared in common with SCCa, with the exception of only 18 genes. Supervised clustering analysis yielded correct classification of lesions in 26/27 (96%) of cases and unsupervised clustering analysis yielded correct classification in 25/27 (92.6%) of cases. Conclusions The results from this analysis suggest that bladder SCCa shares a significant number of gene expression changes with conventional UCa, but also

  3. Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines

    PubMed Central

    Coram, Marc A.; Reddy, Anupama; Deng, Glenn; Telli, Melinda L.; Advani, Ranjana H.; Carlson, Robert W.; Mollick, Joseph A.; Sheth, Shruti; Kurian, Allison W.; Ford, James M.; Stockdale, Frank E.; Quake, Stephen R.; Pease, R. Fabian; Mindrinos, Michael N.; Bhanot, Gyan; Dairkee, Shanaz H.; Davis, Ronald W.; Jeffrey, Stefanie S.

    2012-01-01

    Background To improve cancer therapy, it is critical to target metastasizing cells. Circulating tumor cells (CTCs) are rare cells found in the blood of patients with solid tumors and may play a key role in cancer dissemination. Uncovering CTC phenotypes offers a potential avenue to inform treatment. However, CTC transcriptional profiling is limited by leukocyte contamination; an approach to surmount this problem is single cell analysis. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery. Methodology/Principal Findings We purified CTCs using the MagSweeper, an immunomagnetic enrichment device that isolates live tumor cells from unfractionated blood. CTCs that met stringent criteria for further analysis were obtained from 70% (14/20) of primary and 70% (21/30) of metastatic breast cancer patients; none were captured from patients with non-epithelial cancer (n = 20) or healthy subjects (n = 25). Microfluidic-based single cell transcriptional profiling of 87 cancer-associated and reference genes showed heterogeneity among individual CTCs, separating them into two major subgroups, based on 31 highly expressed genes. In contrast, single cells from seven breast cancer cell lines were tightly clustered together by sample ID and ER status. CTC profiles were distinct from those of cancer cell lines, questioning the suitability of such lines for drug discovery efforts for late stage cancer therapy. Conclusions/Significance For the first time, we directly measured high dimensional gene expression in individual CTCs without the common practice of pooling such cells. Elevated transcript levels of genes associated with metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM, TGFß1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Our findings demonstrate that profiling CTCs

  4. Selection of Novel Peptides Homing the 4T1 CELL Line: Exploring Alternative Targets for Triple Negative Breast Cancer.

    PubMed

    Silva, Vera L; Ferreira, Debora; Nobrega, Franklin L; Martins, Ivone M; Kluskens, Leon D; Rodrigues, Ligia R

    2016-01-01

    The use of bacteriophages to select novel ligands has been widely explored for cancer therapy. Their application is most warranted in cancer subtypes lacking knowledge on how to target the cancer cells in question, such as the triple negative breast cancer, eventually leading to the development of alternative nanomedicines for cancer therapeutics. Therefore, the following study aimed to select and characterize novel peptides for a triple negative breast cancer murine mammary carcinoma cell line- 4T1. Using phage display, 7 and 12 amino acid random peptide libraries were screened against the 4T1 cell line. A total of four rounds, plus a counter-selection round using the 3T3 murine fibroblast cell line, was performed. The enriched selective peptides were characterized and their binding capacity towards 4T1 tissue samples was confirmed by immunofluorescence and flow cytometry analysis. The selected peptides (4T1pep1 -CPTASNTSC and 4T1pep2-EVQSSKFPAHVS) were enriched over few rounds of selection and exhibited specific binding to the 4T1 cell line. Interestingly, affinity to the human MDA-MB-231 cell line was also observed for both peptides, promoting the translational application of these novel ligands between species. Additionally, bioinformatics analysis suggested that both peptides target human Mucin-16. This protein has been implicated in different types of cancer, as it is involved in many important cellular functions. This study strongly supports the need of finding alternative targeting systems for TNBC and the peptides herein selected exhibit promising future application as novel homing peptides for breast cancer therapy.

  5. Selection of Novel Peptides Homing the 4T1 CELL Line: Exploring Alternative Targets for Triple Negative Breast Cancer

    PubMed Central

    Nobrega, Franklin L.; Martins, Ivone M.

    2016-01-01

    The use of bacteriophages to select novel ligands has been widely explored for cancer therapy. Their application is most warranted in cancer subtypes lacking knowledge on how to target the cancer cells in question, such as the triple negative breast cancer, eventually leading to the development of alternative nanomedicines for cancer therapeutics. Therefore, the following study aimed to select and characterize novel peptides for a triple negative breast cancer murine mammary carcinoma cell line– 4T1. Using phage display, 7 and 12 amino acid random peptide libraries were screened against the 4T1 cell line. A total of four rounds, plus a counter-selection round using the 3T3 murine fibroblast cell line, was performed. The enriched selective peptides were characterized and their binding capacity towards 4T1 tissue samples was confirmed by immunofluorescence and flow cytometry analysis. The selected peptides (4T1pep1 –CPTASNTSC and 4T1pep2—EVQSSKFPAHVS) were enriched over few rounds of selection and exhibited specific binding to the 4T1 cell line. Interestingly, affinity to the human MDA-MB-231 cell line was also observed for both peptides, promoting the translational application of these novel ligands between species. Additionally, bioinformatics analysis suggested that both peptides target human Mucin-16. This protein has been implicated in different types of cancer, as it is involved in many important cellular functions. This study strongly supports the need of finding alternative targeting systems for TNBC and the peptides herein selected exhibit promising future application as novel homing peptides for breast cancer therapy. PMID:27548261

  6. Development of a Clinical Tool to Predict Home Death of a Discharged Cancer Patient in Japan: a Case-Control Study.

    PubMed

    Fukui, Sakiko; Morita, Tatsuya; Yoshiuchi, Kazuhiro

    2017-08-01

    The aim of this study was to investigate the predictive value of a clinical tool to predict whether discharged cancer patients die at home, comparing groups of case who died at home and control who died in hospitals or other facilities. We conducted a nationwide case-control study to identify the determinants of home death for a discharged cancer patient. We randomly selected nurses in charge of 2000 home-visit nursing agencies from all 5813 agencies in Japan by referring to the nationwide databases in January 2013. The nurses were asked to report variables of their patients' place of death, patients' and caregivers' clinical statuses, and their preferences for home death. We used logistic regression analysis and developed a clinical tool to accurately predict it and investigated their predictive values. We identified 466 case and 478 control patients. Five predictive variables of home death were obtained: patients' and caregivers' preferences for home death [OR (95% CI) 2.66 (1.99-3.55)], availability of visiting physicians [2.13 (1.67-2.70)], 24-h contact between physicians and nurses [1.68 (1.30-2.18)], caregivers' experiences of deathwatch at home [1.41 (1.13-1.75)], and patients' insights as to their own prognosis [1.23 (1.02-1.50)]. We calculated the scores predicting home death for each variable (range 6-28). When using a cutoff point of 16, home death was predicted with a sensitivity of 0.72 and a specificity of 0.81 with the Harrell's c-statistic of 0.84. This simple clinical tool for healthcare professionals can help predict whether a discharged patient is likely to die at home.

  7. Automated tumor analysis for molecular profiling in lung cancer

    PubMed Central

    Boyd, Clinton; James, Jacqueline A.; Loughrey, Maurice B.; Hougton, Joseph P.; Boyle, David P.; Kelly, Paul; Maxwell, Perry; McCleary, David; Diamond, James; McArt, Darragh G.; Tunstall, Jonathon; Bankhead, Peter; Salto-Tellez, Manuel

    2015-01-01

    The discovery and clinical application of molecular biomarkers in solid tumors, increasingly relies on nucleic acid extraction from FFPE tissue sections and subsequent molecular profiling. This in turn requires the pathological review of haematoxylin & eosin (H&E) stained slides, to ensure sample quality, tumor DNA sufficiency by visually estimating the percentage tumor nuclei and tumor annotation for manual macrodissection. In this study on NSCLC, we demonstrate considerable variation in tumor nuclei percentage between pathologists, potentially undermining the precision of NSCLC molecular evaluation and emphasising the need for quantitative tumor evaluation. We subsequently describe the development and validation of a system called TissueMark for automated tumor annotation and percentage tumor nuclei measurement in NSCLC using computerized image analysis. Evaluation of 245 NSCLC slides showed precise automated tumor annotation of cases using Tissuemark, strong concordance with manually drawn boundaries and identical EGFR mutational status, following manual macrodissection from the image analysis generated tumor boundaries. Automated analysis of cell counts for % tumor measurements by Tissuemark showed reduced variability and significant correlation (p < 0.001) with benchmark tumor cell counts. This study demonstrates a robust image analysis technology that can facilitate the automated quantitative analysis of tissue samples for molecular profiling in discovery and diagnostics. PMID:26317646

  8. Psychopathological profile of women with breast cancer based on the symptom checklist-90-R.

    PubMed

    Pan, Xiong-Fei; Fei, Man-Dong; Zhang, Kenneth Y; Fan, Zhen-Lie; Fu, Feng-Huan; Fan, Jin-Hu

    2014-01-01

    With effective early treatments, many breast cancer patients suffer from psychological distress due to adverse effects and lifelong physical disfigurement. Our study aimed to evaluate the psychopathological profile of breast cancer patients in comparison with healthy women and explored demographic correlates. We consecutively enrolled breast cancer patients who came to the hospital for follow-up or rehabilitation care after primary treatment, and healthy female relatives or friends of inpatients in the Cancer Institute of Chinese Academy of Medical Sciences between August 30, 2010 and January 1, 2012. Psychopathological profile was assessed based on the Symptom Checklist-90-R (SCL-90-R) for patients and controls. We compared demographics such as age, ethnicity, education, marriage, and occupation, and incorporated these data plus cancer status for the association with the general SCL-90-R index and scores for 9 major symptom dimensions in multiple regression analysis. We surveyed a total of 291 female breast cancer patients and 531 healthy women. The average age was 55.1 ± 6.40 years for breast cancer patients and 43.1 ± 12.8 for healthy controls (P<0.01). The mean survival was 5.20 years for cancer patients (range, 0.60-9.90 years). There were statistically significant differences in education, marriage, and occupation between the two groups (P<0.01). General index (1.45 ± 0.45 versus 1.32 ± 0.37) and 8 dimension scores (excluding anxiety) on SCL-90-R were significantly higher in patients (P<0.05). Multiple regression analysis showed that the breast cancer status was positively correlated with general SCL-90-R index and 6 dimension scores (excluding the anxiety, phobic anxiety and paranoid ideation dimensions) (P<0.05). Regression coefficients ranged from 0.10 (depression) to 0.19 (somatization). Higher interpersonal sensitivity was noticed in single women compared to married women. Chinese patients with breast cancer demonstrate greater psychopathology

  9. Gene Expression Profiling of Breast Cancer Brain Metastasis

    PubMed Central

    Lee, Ji Yun; Park, Kyunghee; Lee, Eunjin; Ahn, TaeJin; Jung, Hae Hyun; Lim, Sung Hee; Hong, Mineui; Do, In-Gu; Cho, Eun Yoon; Kim, Duk-Hwan; Kim, Ji-Yeon; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2016-01-01

    The biology of breast cancer brain metastasis (BCBM) is poorly understood. We aimed to explore genes that are implicated in the process of brain metastasis of primary breast cancer (BC). NanoString nCounter Analysis covering 252 target genes was used for comparison of gene expression levels between 20 primary BCs that relapsed to brain and 41 BCBM samples. PAM50-based intrinsic subtypes such as HER2-enriched and basal-like were clearly over-represented in BCBM. A panel of 22 genes was found to be significantly differentially expressed between primary BC and BCBM. Five of these genes, CXCL12, MMP2, MMP11, VCAM1, and MME, which have previously been associated with tumor progression, angiogenesis, and metastasis, clearly discriminated between primary BC and BCBM. Notably, the five genes were significantly upregulated in primary BC compared to BCBM. Conversely, SOX2 and OLIG2 genes were upregulated in BCBM. These genes may participate in metastatic colonization but not in primary tumor development. Among patient-matched paired samples (n = 17), a PAM50 molecular subtype conversion was observed in eight cases (47.1%), with a trend toward unfavorable subtypes in patients with the distinct gene expression. Our findings, although not conclusive, reveal differentially expressed genes that might mediate the brain metastasis process. PMID:27340107

  10. The utilization of formal and informal home care by older patients with cancer: a Belgian cohort study with two control groups.

    PubMed

    Baitar, Abdelbari; Buntinx, Frank; De Burghgraeve, Tine; Deckx, Laura; Bulens, Paul; Wildiers, Hans; van den Akker, Marjan

    2017-09-12

    The purpose of this paper is to analyse the utilization of formal and informal home care among older patients with cancer (OCP) and to compare this with middle-aged patients with cancer (MCP) and older patients without cancer (ONC). Additionally, we examined predictors of transitions towards formal care one year after a cancer diagnosis. OCP and MCP had to be recruited within three months after a cancer diagnosis and have an estimated life expectancy over six months. ONC consisted of patients without known cancer, seen by the general practitioner. Formal and informal care were compared between the patient groups at baseline, i.e. shortly after a cancer diagnosis and changes in care were studied after one year. A total of 844 patients were evaluable for formal care at baseline and 469 patients (56%) at follow-up. At baseline, about half of older adults and 18% of MCP used formal care, while about 85% of cancer patients and 57% ONC used informal care. Formal care increased for all groups after one year though not significantly in OCP. The amount of informal care only changed in MCP which decreased after one year. Cancer-related factors and changes in need factors predict a transition towards formal care after a cancer diagnosis. A cancer diagnosis has a different impact on the use of formal and informal care than ageing as such. The first year after a cancer diagnosis is an important time to follow-up on the patients' needs for home care.

  11. Cell Surface-Specific N-Glycan Profiling in Breast Cancer

    PubMed Central

    Yao, Yuanfei; Maitikabili, Alaiyi; Qu, Youpeng; Shi, Shuliang; Chen, Cuiying; Li, Yu

    2013-01-01

    Aberrant changes in specific glycans have been shown to be associated with immunosurveillance, tumorigenesis, tumor progression and metastasis. In this study, the N-glycan profiling of membrane proteins from human breast cancer cell lines and tissues was detected using modified DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). The N-glycan profiles of membrane proteins were analyzed from 7 breast cancer cell lines and MCF 10A, as well as from 100 pairs of breast cancer and corresponding adjacent tissues. The results showed that, compared with the matched adjacent normal tissue samples, two biantennary N-glycans (NA2 and NA2FB) were significantly decreased (p <0.0001) in the breast cancer tissue samples, while the triantennary glycan (NA3FB) and a high-mannose glycan (M8) were dramatically increased (p = 0.001 and p <0.0001, respectively). Moreover, the alterations in these specific N-glycans occurred through the oncogenesis and progression of breast cancer. These results suggested that the modified method based on DSA-FACE is a high-throughput detection technology that is suited for analyzing cell surface N-glycans. These cell surface-specific N-glycans may be helpful in recognizing the mechanisms of tumor cell immunologic escape and could be potential targets for new breast cancer drugs. PMID:24009699

  12. Gene Expression Profiling in Hereditary, BRCA1-linked Breast Cancer: Preliminary Report

    PubMed Central

    2006-01-01

    Global analysis of gene expression by DNA microarrays is nowadays a widely used tool, especially relevant for cancer research. It helps the understanding of complex biology of cancer tissue, allows identification of novel molecular markers, reveals previously unknown molecular subtypes of cancer that differ by clinical features like drug susceptibility or general prognosis. Our aim was to compare gene expression profiles in breast cancer that develop against a background of inherited predisposing mutations versus sporadic breast cancer. In this preliminary study we analysed seven hereditary, BRCA1 mutation-linked breast cancer tissues and seven sporadic cases that were carefully matched by histopathology and ER status. Additionally, we analysed 6 samples of normal breast tissue. We found that while the difference in gene expression profiles between tumour tissue and normal breast can be easily recognized by unsupervised algorithms, the difference between those two types of tumours is more discrete. However, by supervised methods of data analysis, we were able to select a set of genes that may differentiate between hereditary and sporadic tumours. The most significant difference concerns genes that code for proteins engaged in regulation of transcription, cellular metabolism, signalling, proliferation and cell death. Microarray results for chosen genes (TOB1, SEPHS2) were validated by real-time RT-PCR. PMID:20223001

  13. Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines

    PubMed Central

    Campbell, James; Ryan, Colm J.; Brough, Rachel; Bajrami, Ilirjana; Pemberton, Helen N.; Chong, Irene Y.; Costa-Cabral, Sara; Frankum, Jessica; Gulati, Aditi; Holme, Harriet; Miller, Rowan; Postel-Vinay, Sophie; Rafiq, Rumana; Wei, Wenbin; Williamson, Chris T.; Quigley, David A.; Tym, Joe; Al-Lazikani, Bissan; Fenton, Timothy; Natrajan, Rachael; Strauss, Sandra J.; Ashworth, Alan; Lord, Christopher J.

    2016-01-01

    Summary One approach to identifying cancer-specific vulnerabilities and therapeutic targets is to profile genetic dependencies in cancer cell lines. Here, we describe data from a series of siRNA screens that identify the kinase genetic dependencies in 117 cancer cell lines from ten cancer types. By integrating the siRNA screen data with molecular profiling data, including exome sequencing data, we show how vulnerabilities/genetic dependencies that are associated with mutations in specific cancer driver genes can be identified. By integrating additional data sets into this analysis, including protein-protein interaction data, we also demonstrate that the genetic dependencies associated with many cancer driver genes form dense connections on functional interaction networks. We demonstrate the utility of this resource by using it to predict the drug sensitivity of genetically or histologically defined subsets of tumor cell lines, including an increased sensitivity of osteosarcoma cell lines to FGFR inhibitors and SMAD4 mutant tumor cells to mitotic inhibitors. PMID:26947069

  14. Analytical validation of serum proteomic profiling for diagnosis of prostate cancer: sources of sample bias.

    PubMed

    McLerran, Dale; Grizzle, William E; Feng, Ziding; Bigbee, William L; Banez, Lionel L; Cazares, Lisa H; Chan, Daniel W; Diaz, Jose; Izbicka, Elzbieta; Kagan, Jacob; Malehorn, David E; Malik, Gunjan; Oelschlager, Denise; Partin, Alan; Randolph, Timothy; Rosenzweig, Nicole; Srivastava, Shiv; Srivastava, Sudhir; Thompson, Ian M; Thornquist, Mark; Troyer, Dean; Yasui, Yutaka; Zhang, Zhen; Zhu, Liu; Semmes, O John

    2008-01-01

    This report and a companion report describe a validation of the ability of serum proteomic profiling via SELDI-TOF mass spectrometry to detect prostatic cancer. Details of this 3-stage process have been described. This report describes the development of the algorithm and results of the blinded test for stage 1. We derived the decision algorithm used in this study from the analysis of serum samples from patients with prostate cancer (n = 181) and benign prostatic hyperplasia (BPH) (n = 143) and normal controls (n = 220). We also derived a validation test set from a separate, geographically diverse set of serum samples from 42 prostate cancer patients and 42 controls without prostate cancer. Aliquots were subjected to randomization and blinded analysis, and data from each laboratory site were subjected to the decision algorithm and decoded. Using the data collected from the validation test set, the decision algorithm was unsuccessful in separating cancer from controls with any predictive utility. Analysis of the experimental data revealed potential sources of bias. The ability of the decision algorithm to successfully differentiate between prostate cancer, BPH, and control samples using data derived from serum protein profiling was compromised by bias.

  15. Metabolic Profile of Breast Cancer in a Population of Women in Southern Spain

    PubMed Central

    Lopez-Saez, Juan-Bosco; Martinez-Rubio, Jose Antonio; Alvarez, Maria Montes; Carrera, Carmen Gonzalez; Dominguez Villar, Margarita; de Lomas Mier, Antonio Garcia; Doménech, Charo; Senra-Varela, Avelino

    2008-01-01

    Background: There are indications that mortality in breast cancer is related with dietary factors, but no study has been large enough to characterise reliably how, this risk is influenced. To establish a logistic regression equation that would predict breast cancer from factors in the endocrinological and metabolic profile, we studied endocrinological and metabolic risk factors that are modified by the diet, in a population of women with breast cancer in southern Spain. Patients and Methods: We carried out a simple a case-control study comparing 204 women with breast cancer (96 premenopausal and 108 postmenopausal women) and 250 healthy control subjects. The predictive variables were basal glycaemia, insulin, glycosylated haemoglobin (HbA1c), C-peptide, insulin-like growth factor-I (IGF-I), total cholesterol, triglycerides, high density lipoprotein-c (HDL-C), low density lipoprotein-c (LDL-C), selenium and Quetelet index (BMI). Results: The metabolic profile differed between pre- and postmenopausal patients, and metabolic alterations were greater in postmenopausal than in premenopausal women. The differences between healthy subjects and breast cancer patients were clearly significant. Conclusions: Our findings have several potential practical applications in the early detection of breast cancer, especially in premenopausal women; in primary prevention; and in the development of a mathematical model of breast carcinogenesis. PMID:18665244

  16. Variability in statin-induced changes in gene expression profiles of pancreatic cancer

    PubMed Central

    Gbelcová, Helena; Rimpelová, Silvie; Ruml, Tomáš; Fenclová, Marie; Kosek, Vítek; Hajšlová, Jana; Strnad, Hynek; Kolář, Michal; Vítek, Libor

    2017-01-01

    Statins, besides being powerful cholesterol-lowering drugs, also exert potent anti-proliferative activities. However, their anti-cancer efficacy differs among the individual statins. Thus, the aim of this study was to identify the biological pathways affected by individual statins in an in vitro model of human pancreatic cancer. The study was performed on a human pancreatic cancer cell line MiaPaCa-2, exposed to all commercially available statins (12 μM, 24 h exposure). DNA microarray analysis was used to determine changes in the gene expression of treated cells. Intracellular concentrations of individual statins were measured by UPLC (ultra performance liquid chromatography)-HRMS (high resolution mass spectrometer). Large differences in the gene transcription profiles of pancreatic cancer cells exposed to various statins were observed; cerivastatin, pitavastatin, and simvastatin being the most efficient modulators of expression of genes involved namely in the mevalonate pathway, cell cycle regulation, DNA replication, apoptosis and cytoskeleton signaling. Marked differences in the intracellular concentrations of individual statins in pancreatic cancer cells were found (>11 times lower concentration of rosuvastatin compared to lovastatin), which may contribute to inter-individual variability in their anti-cancer effects. In conclusion, individual statins exert different gene expression modulating effects in treated pancreatic cancer cells. These effects may be partially caused by large differences in their bioavailability. We report large differences in gene transcription profiles of pancreatic cancer cells exposed to various statins. These data correlate to some extent with the intracellular concentrations of statins, and may explain the inter-individual variability in the anti-cancer effects of statins. PMID:28276528

  17. Circulating microRNA Profiling Identifies a Subset of Metastatic Prostate Cancer Patients with Evidence of Cancer-Associated Hypoxia

    PubMed Central

    Kroh, Evan M.; Dowell, Alexander E.; Chéry, Lisly; Siddiqui, Javed; Nelson, Peter S.; Vessella, Robert L.; Knudsen, Beatrice S.; Chinnaiyan, Arul M.; Pienta, Kenneth J.; Morrissey, Colm; Tewari, Muneesh

    2013-01-01

    MicroRNAs (miRNAs) are small (∼22 nucleotide) non-coding RNAs that regulate a myriad of biological processes and are frequently dysregulated in cancer. Cancer-associated microRNAs have been detected in serum and plasma and hold promise as minimally invasive cancer biomarkers, potentially for assessing disease characteristics in patients with metastatic disease that is difficult to biopsy. Here we used miRNA profiling to identify cancer-associated miRNAs that are differentially expressed in sera from patients with metastatic castration resistant prostate cancer (mCRPC) as compared to healthy controls. Of 365 miRNAs profiled, we identified five serum miRNAs (miR-141, miR-200a, miR-200c, miR-210 and miR-375) that were elevated in cases compared to controls across two independent cohorts. One of these, miR-210, is a known transcriptional target of the hypoxia-responsive HIF-1α signaling pathway. Exposure of cultured prostate cancer cells to hypoxia led to induction of miR-210 and its release into the extracellular environment. Moreover, we found that serum miR-210 levels varied widely amongst mCRPC patients undergoing therapy, and correlated with treatment response as assessed by change in PSA. Our results suggest that (i) cancer-associated hypoxia is a frequent, previously under-appreciated characteristic of mCRPC, and (ii) serum miR-210 may be further developed as a predictive biomarker in patients with this distinct disease biology. PMID:23935962

  18. Detecting pan-cancer conserved microRNA modules from microRNA expression profiles across multiple cancers.

    PubMed

    Liu, Zhaowen; Zhang, Junying; Yuan, Xiguo; Liu, Baobao; Liu, Yajun; Li, Aimin; Zhang, Yuanyuan; Sun, Xiaohan; Tuo, Shouheng

    2015-08-01

    MicroRNAs (miRNAs) play an indispensable role in cancer initiation and progression. Different cancers have some common hallmarks in general. Analyzing miRNAs that consistently contribute to different cancers can help us to discover the relationship between miRNAs and traits shared by cancers. Most previous works focus on analyzing single miRNA. However, dysregulation of a single miRNA is generally not sufficient to contribute to complex cancer processes. In this study, we put emphasis on analyzing cooperation of miRNAs across cancers. We assume that miRNAs can cooperatively regulate oncogenic pathways and contribute to cancer hallmarks. Such a cooperation is modeled by a miRNA module referred to as a pan-cancer conserved miRNA module. The module consists of miRNAs which simultaneously regulate cancers and are significantly intra-correlated. A novel computational workflow for the module discovery is presented. Multiple modules are discovered from miRNA expression profiles using the method. The function of top two ranked modules are analyzed using the mRNAs which correlate to all the miRNAs in a module across cancers, inferring that the two modules function in regulating the cell cycle which relates to cancer hallmarks as self sufficiency in growth signals and insensitivity to antigrowth signals. Additionally, two novel miRNAs mir-590 and mir-629 are found to cooperate with well-known onco-miRNAs in the modules to contribute to cancers. We also found that PTEN, which is a well known tumor suppressor that regulates the cell cycle, is a common target of miRNAs in the top-one module and cooperative control of PTEN can be a reason for the miRNAs' cooperation. We believe that analyzing the cooperative mechanism of the miRNAs in modules rather than focusing on only single miRNAs may help us know more about the complicated relationship between miRNAs and cancers and develop more effective treatment strategies for cancers.

  19. 1-stearoylglycerol is associated with risk of prostate cancer: results from serum metabolomic profiling.

    PubMed

    Mondul, Alison M; Moore, Steven C; Weinstein, Stephanie J; Männistö, Satu; Sampson, Joshua N; Albanes, Demetrius

    2014-10-01

    Although prostate cancer is the most commonly diagnosed cancer among men in developed populations, recent recommendations against routine prostate-specific antigen screening have cast doubt on its utility for early detection. We compared the metabolomic profiles of prospectively collected fasting serum from 74 prostate cancer cases and 74 controls selected from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of male smokers. Circulating 1-stearoylglycerol (1-SG, or 1-monostearin) was statistically significantly inversely associated with risk of prostate cancer after Bonferroni correction for multiple comparisons (i.e., 420 identified metabolites) (OR=0.34, 95% CI=0.20 - 0.58, p=6.3 × 10(-5)). The magnitude of this association did not differ by disease aggressiveness and was observed for cases diagnosed up to 23 years after blood collection. Similar but somewhat weaker prostate cancer risk signals were also evident for glycerol and alpha-ketoglutarate. In this population, men with higher serum 1-SG were less likely to develop prostate cancer, supporting a role for dysregulation of lipid metabolism in this malignancy. Additional studies are needed to retest the association and to examine 1-SG for its potential as a prostate cancer early detection marker.

  20. Hormone profiles in women treated for cervical cancer

    SciTech Connect

    Eby, N.L.

    1986-01-01

    Some investigators believe that the protective effect of radiotherapy is hormonally mediated. To determine whether ovarian radiation affects serum hormone levels differently from surgical removal of the ovaries, serum estradiol, estrone, testosterone and androstenedione were evaluated by radioimmunoassay in 320 women (203 irradiated and 117 nonirradiated) from six US clinics participating in a large international cohort study of women treated for cervical cancer since the 1960's. Overall, estradiol levels were similar for both treatment groups, while estrone, testosterone and androstenedione levels were somewhat lower in irradiated women than in nonirradiated women after adjustment for year of birth. Notably, among women in both groups whose treatment included bilateral oophorectomy, irradiated women consistently had lower levels of androstenedione, testosterone and estrone but similar levels of estradiol.

  1. Cohort profile: the skin cancer after organ transplant study.

    PubMed

    Madeleine, Margaret M; Johnson, Lisa G; Daling, Janet R; Schwartz, Stephen M; Carter, Joseph J; Berg, Daniel; Nelson, Karen; Davis, Connie L; Galloway, Denise A

    2013-12-01

    The Skin Cancer after Organ Transplant (SCOT) study was designed to investigate the link between genus beta human papillomavirus (HPV) and squamous cell skin cancer (SCSC). We focused on a population receiving immunosuppressive therapy for extended periods, transplant patients, as they are at extremely high risk for developing SCSC. Two complementary projects were conducted in the Seattle area: (i) a retrospective cohort with interview data from 2004 recipients of renal or cardiac transplants between 1995 and 2010 and (ii) a prospective cohort with interview data from 328 people on the transplant waiting lists between 2009 and 2011. Within the retrospective cohort, we developed a nested case-control study (172 cases and 337 control subjects) to assess risk of SCSC associated with markers of HPV in SCSC tumour tissue and eyebrow hair bulb DNA (HPV genotypes) and blood (HPV antibodies). In the prospective cohort, 135 participants had a 1-year post-transplant visit and 71 completed a 2-year post-transplant visit. In both arms of the cohort, we collected samples to assess markers of HPV infection such as acquisition of new types, proportion positive for each type, persistence of types at consecutive visits and number of HPV types detected. In the prospective cohort, we will also examine these HPV markers in relation to levels of cell-mediated immunity. The goal of the SCOT study is to use the data we collected to gain a more complete understanding of the role of immune suppression in HPV kinetics and of genus beta HPV types in SCSC. For more information, please contact the principal investigator through the study website: http://www.fhcrc.org/science/phs/cerc/The_SCOT_Study.html.

  2. Cancer trends in Kashmir; common types, site incidence and demographic profiles: National Cancer Registry 2000-2012.

    PubMed

    Wani, M A; Jan, F A; Khan, N A; Pandita, K K; Khurshid, R; Khan, S H

    2014-01-01

    An assessment of cancer incidence in population is required for prevention, early diagnosis, treatment and resource allocation. This will also guide in the formation of facilities for diagnosis, treatment, rehabilitation and follow-up for these patients. The demographic trend of cancer will help to identify common types and etiological factors. Efforts at clinical, research and administrative levels are needed to overcome this problem. Present retro prospective study was conducted in regional cancer center of a tertiary care hospital. After permission from ethics committee, a retro prospective study of 1 year duration was undertaken to study the profile of cancer patients and to compare it with other cancer registries in India. Pearson's Chi-square test and simple linear regression were used. Statistical Package for the Social Sciences version-16 (University of Bristol information services (www.bristol.ac.uk/is/learning/resources) was used. The overall incidence of cancer in Kashmir is on the increase and common sites of cancer are esophagus and gastroesophageal (GE) junction, lung, stomach, colorectal, lymphomas, skin, laryngopharynx, acute leukemias, prostate and brain in males.In females common sites are breast, esophagus and GE junction, ovary, colorectal, stomach, lung, gallbladder, lymphomas, acute leukemias and brain. Cancers of esophagus, stomach and lungs have a high incidence both in men and women in Kashmir. Future studies on sources and types of environmental pollution and exposures in relation to these cancers may improve our understanding of risk factors held responsible for causation of these malignancies in this region. This will help in the allocation of available resources for prevention and treatment strategies.

  3. Home care by general practitioners for cancer patients in the last 3 months of life: An epidemiological study of quality and associated factors

    PubMed Central

    Pivodic, Lara; Harding, Richard; Calanzani, Natalia; McCrone, Paul; Hall, Sue; Deliens, Luc; Higginson, Irene J; Gomes, Barbara

    2016-01-01

    Background: Stronger generalist end-of-life care at home for people with cancer is called for but the quality of end-of-life care delivered by general practitioners has been questioned. Aim: To determine the degree of and factors associated with bereaved relatives’ satisfaction with home end-of-life care delivered by general practitioners to cancer patients. Design: Population-based mortality followback survey. Setting/participants: Bereaved relatives of people who died of cancer in London, United Kingdom (identified from death registrations in 2009–2010), were invited to complete a postal questionnaire surveying the deceased’s final 3 months of life. Results: Questionnaires were completed for 596 decedents of whom 548 spent at least 1 day at home in the last 3 months of life. Of the respondents, 55% (95% confidence interval: 51%–59%) reported excellent/very good home care by general practitioners, compared with 78% (95% confidence interval: 74%–82%) for specialist palliative care providers and 68% (95% confidence interval: 64%–73%) for district/community/private nurses. The odds of high satisfaction (excellent/very good) with end-of-life care by general practitioners doubled if general practitioners made three or more compared with one or no home visits in the patient’s last 3 months of life (adjusted odds ratio: 2.54 (95% confidence interval: 1.52–4.24)) and halved if the patient died at hospital rather than at home (adjusted odds ratio: 0.55 (95% confidence interval: 0.31–0.998)). Conclusion: There is considerable room for improvement in the satisfaction with home care provided by general practitioners to terminally ill cancer patients. Ensuring an adequate offer of home visits by general practitioners may help to achieve this goal. PMID:26036688

  4. Economic and patient-reported outcomes of outpatient home-based versus inpatient hospital-based chemotherapy for patients with colorectal cancer.

    PubMed

    Joo, Eun-Hye; Rha, Sun-Young; Ahn, Joong Bae; Kang, Hye-Young

    2011-07-01

    This study aims to compare the economic- and patient-reported outcomes between outpatient home-based and inpatient hospital-based chemotherapy in advanced colorectal cancer patients. A total of 80 patients from Severance Hospital in Seoul, Korea, who had stage III colorectal cancer and underwent home-based (n = 40) or hospital-based chemotherapy (n = 40) with a FOLFOX regimen between January 2007 and April 2008 were enrolled. Patient satisfaction data were collected by a self-administered questionnaire survey. Based on hospital charge records, average cost (in 2008 Korean won (KW)) per chemotherapy session was estimated and compared between home- and hospital-based chemotherapy from a societal perspective. Patients receiving chemotherapy at home showed higher satisfaction with their treatment (mean satisfaction score 3.58 ± 0.15, 5-point Likert-type scale, with a higher score indicating higher satisfaction) than did those treated at the hospital (3.23 ± 0.21; p < 0.01). After adjusting for differences in baseline characteristics between the two groups using multivariate analysis, those receiving home-based chemotherapy still showed significantly higher satisfaction than those undergoing hospital-based therapy (β = 0.271, p < 0.001). Additionally, home-based therapy reduced the cost per chemotherapy session by 16.6%, compared with hospital-based treatment (1,694,216 versus 2,030,383 KW, 1,200 KW ≈ 1 US dollar). The largest cost reduction was attributable to medical costs (-201,122 KW), followed by caregiver's opportunity costs (-135,000 KW). Higher satisfaction and lower economic cost for home-based chemotherapy suggests that home-based chemotherapy could be a popular and cost-effective treatment option for colorectal cancer patients who are eligible for home-based chemotherapy.

  5. Differential variability improves the identification of cancer risk markers in DNA methylation studies profiling precursor cancer lesions.

    PubMed

    Teschendorff, Andrew E; Widschwendter, Martin

    2012-06-01

    The standard paradigm in omic disciplines has been to identify biologically relevant biomarkers using statistics that reflect differences in mean levels of a molecular quantity such as mRNA expression or DNA methylation. Recently, however, it has been proposed that differential epigenetic variability may mark genes that contribute to the risk of complex genetic diseases like cancer and that identification of risk and early detection markers may therefore benefit from statistics based on differential variability. Using four genome-wide DNA methylation datasets totalling 311 epithelial samples and encompassing all stages of cervical carcinogenesis, we here formally demonstrate that differential variability, as a criterion for selecting DNA methylation features, can identify cancer risk markers more reliably than statistics based on differences in mean methylation. We show that differential variability selects features with heterogeneous outlier methylation profiles and that these play a key role in the early stages of carcinogenesis. Moreover, differentially variable features identified in precursor non-invasive lesions exhibit significantly increased enrichment for developmental genes compared with differentially methylated sites. Conversely, differential variability does not add predictive value in cancer studies profiling invasive tumours or whole-blood tissue. Finally, we incorporate the differential variability feature selection step into a novel adaptive index prediction algorithm called EVORA (epigenetic variable outliers for risk prediction analysis), and demonstrate that EVORA compares favourably to powerful prediction algorithms based on differential methylation statistics. Statistics based on differential variability improve the detection of cancer risk markers in the context of DNA methylation studies profiling epithelial preinvasive neoplasias. We present a novel algorithm (EVORA) which could be used for prediction and diagnosis of precursor epithelial

  6. Plasma Biomarker Profiles Differ Depending on Breast Cancer Subtype but RANTES is Consistently Increased

    SciTech Connect

    Gonzales, Rachel M.; Daly, Don S.; Tan, Ruimin; Marks, Jeffrey R.; Zangar, Richard C.

    2011-07-01

    Background: Current biomarkers for breast cancer have little potential for detection. We determined if breast cancer subtypes influence circulating protein biomarkers. Methods: A sandwich-ELISA microarray platform was used to evaluate 23 candidate biomarkers in plasma samples that were obtained from subjects with either benign breast disease or invasive breast cancer. All plasma samples were collected at the time of biopsy, after a referral due to a suspicious screen (e.g., mammography). Cancer samples were evaluated based on breast cancer subtypes, as defined by the HER2 and estrogen receptor statuses. Results: Ten proteins were statistically altered in at least one breast cancer subtype, including four epidermal growth factor receptor ligands, two matrix metalloproteases, two cytokines, and two angiogenic factors. Only one cytokine, RANTES, was significantly increased (P<0.01 for each analysis) in all four subtypes, with areas under receiver operating characteristic curves (AUC) that ranged from 0.76 to 0.82, depending on cancer subtype. The best AUC values were observed for analyses that combined data from multiple biomarkers, with values ranging from 0.70 to 0.99, depending on the cancer subtype. Although the results for RANTES are consistent with previous publications, the multi-assay results need to be validated in independent sample sets. Conclusions: Different breast cancer subtypes produce distinct biomarker profiles, and circulating protein biomarkers have potential to differentiate between true and false positive screens for breast cancer. Impact: Subtype-specific biomarker panels may be useful for detecting breast cancer or as an adjunct assay to improve the accuracy of current screening methods.

  7. Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression.

    PubMed

    Putluri, Nagireddy; Shojaie, Ali; Vasu, Vihas T; Vareed, Shaiju K; Nalluri, Srilatha; Putluri, Vasanta; Thangjam, Gagan Singh; Panzitt, Katrin; Tallman, Christopher T; Butler, Charles; Sana, Theodore R; Fischer, Steven M; Sica, Gabriel; Brat, Daniel J; Shi, Huidong; Palapattu, Ganesh S; Lotan, Yair; Weizer, Alon Z; Terris, Martha K; Shariat, Shahrokh F; Michailidis, George; Sreekumar, Arun

    2011-12-15

    Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.

  8. Bereaved family members' perspectives on suffering among older rural cancer patients in palliative home nursing care: A qualitative study.

    PubMed

    Devik, S A; Hellzen, O; Enmarker, I

    2016-11-17

    Little is known about experiences with receiving home nursing care when old, living in a rural area, and suffering from end-stage cancer. The aim of this study was thus to investigate bereaved family members' perceptions of suffering by their older relatives when receiving palliative home nursing care. Qualitative semi-structured interviews were conducted with 10 family members, in Norway during autumn 2015, and directed content analysis guided by Katie Eriksson's theoretical framework on human suffering was performed upon the data. The two main categories identified reflected expressions of both suffering and well-being. Expressions of suffering were related to illness, to care and to life and supported the theory. Expressions of well-being were related to other people (e.g. familiar people and nurses), to home and to activity. The results indicate a need to review and possibly expand the perspective of what should motivate care. Nursing and palliative care that become purely disease and symptom-focused may end up with giving up and divert the attention to social and cultural factors that may contribute to well-being when cure is not the goal.

  9. Addressing Methodological Challenges in Large Communication Datasets: Collecting and Coding Longitudinal Interactions in Home Hospice Cancer Care

    PubMed Central

    Reblin, Maija; Clayton, Margaret F; John, Kevin K; Ellington, Lee

    2015-01-01

    In this paper, we present strategies for collecting and coding a large longitudinal communication dataset collected across multiple sites, consisting of over 2000 hours of digital audio recordings from approximately 300 families. We describe our methods within the context of implementing a large-scale study of communication during cancer home hospice nurse visits, but this procedure could be adapted to communication datasets across a wide variety of settings. This research is the first study designed to capture home hospice nurse-caregiver communication, a highly understudied location and type of communication event. We present a detailed example protocol encompassing data collection in the home environment, large-scale, multi-site secure data management, the development of theoretically-based communication coding, and strategies for preventing coder drift and ensuring reliability of analyses. Although each of these challenges have the potential to undermine the utility of the data, reliability between coders is often the only issue consistently reported and addressed in the literature. Overall, our approach demonstrates rigor and provides a “how-to” example for managing large, digitally-recorded data sets from collection through analysis. These strategies can inform other large-scale health communication research. PMID:26580414

  10. Tolerability profile of bevacizumab in metastatic colorectal cancer: about a Medical Department experience

    PubMed Central

    Khmamouche, Mohamed Reda; Mahfoud, Tarik; Bazine, Aziz; Tanz, Rachid; Ichou, Mohamed; Errihani, Hassan

    2016-01-01

    Colorectal cancer is one of the most common cancers worldwide, and associated with high mortality rates in our country. The prognosis of patients diagnosed with metastatic colorectal cancer (mCRC) has improved markedly over the last 12 years, increasing from 5 months with best supportive care to almost 2 years with combination chemotherapy plus bevacizumab. Bevacizumab is well suited for use in combination with first or second line chemotherapy in the treatment of mCRC because its side effects are predictable and appear not to add to the incidence or severity of the side effects of chemotherapy. The aim of our small study is to explore the tolerability profile of bevacizumab used in daily clinical practice in patients with metastatic colorectal cancer (mCRC) in our department. PMID:28292081

  11. Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies

    PubMed Central

    Arslan‐Low, Elif; Kabir, Musarat; Worthington, Jenny; Camuzeaux, Stephane; Sinclair, John; Szaub, Joanna; Afrough, Babak; Podust, Vladimir N.; Fourkala, Evangelia‐Ourania; Cubizolles, Myriam; Kronenberg, Florian; Fung, Eric T.; Gentry‐Maharaj, Aleksandra; Menon, Usha; Jacobs, Ian

    2014-01-01

    Purpose Ovarian cancer is a devastating disease and biomarkers for its early diagnosis are urgently required. Serum may be a valuable source of biomarkers that may be revealed by proteomic profiling. Herein, complementary serum protein profiling strategies were employed for discovery of biomarkers that could discriminate cases of malignant and benign ovarian cancer. Experimental design Identically collected and processed serum samples from 22 cases of invasive epithelial ovarian cancer, 45 benign ovarian neoplasms, and 64 healthy volunteers were subjected to immunodepletion and protein equalization coupled to 2D‐DIGE/MS and multidimensional fractionation coupled to SELDI‐TOF profiling with MS/MS for protein identification. Selected candidates were verified by ELISA in samples from malignant (n = 70) and benign (n = 89) cases and combined marker panels tested against serum CA125. Results Both profiling platforms were complementary in identifying biomarker candidates, four of which (A1AT, SLPI, APOA4, VDBP) significantly discriminated malignant from benign cases. However, no combination of markers was as good as CA125 for diagnostic accuracy. SLPI was further tested as an early marker using prediagnosis serum samples. While it rose in cases toward diagnosis, it did not discriminate prediagnosis cases from controls. Conclusions and clinical relevance The candidate biomarkers warrant further validation in independent sample sets. PMID:25290619

  12. Computational Cell Cycle Profiling of Cancer Cells for Prioritizing FDA-Approved Drugs with Repurposing Potential.

    PubMed

    Lo, Yu-Chen; Senese, Silvia; France, Bryan; Gholkar, Ankur A; Damoiseaux, Robert; Torres, Jorge Z

    2017-09-12

    Discovery of first-in-class medicines for treating cancer is limited by concerns with their toxicity and safety profiles, while repurposing known drugs for new anticancer indications has become a viable alternative. Here, we have developed a new approach that utilizes cell cycle arresting patterns as unique molecular signatures for prioritizing FDA-approved drugs with repurposing potential. As proof-of-principle, we conducted large-scale cell cycle profiling of 884 FDA-approved drugs. Using cell cycle indexes that measure changes in cell cycle profile patterns upon chemical perturbation, we identified 36 compounds that inhibited cancer cell viability including 6 compounds that were previously undescribed. Further cell cycle fingerprint analysis and 3D chemical structural similarity clustering identified unexpected FDA-approved drugs that induced DNA damage, including clinically relevant microtubule destabilizers, which was confirmed experimentally via cell-based assays. Our study shows that computational cell cycle profiling can be used as an approach for prioritizing FDA-approved drugs with repurposing potential, which could aid the development of cancer therapeutics.

  13. MicroRNA expression profiling in cancer from a bioinformatics prospective.

    PubMed

    Gusev, Yuriy; Brackett, Daniel J

    2007-11-01

    A new type of noncoding short single-stranded RNA molecules, microRNA (miRNA), has recently emerged as one of the most important new classes of cellular regulators. Recent advances in miRNA research have provided evidence that aberrant expression of specific miRNAs is associated with a broad spectrum of human diseases, such as cancer, diabetes, cardiovascular diseases, psychological disorders and others. Global microRNAome profiling has demonstrated drastic changes in expression of multiple miRNAs in many common human cancers. miRNA expression signatures have been shown to provide a more accurate method of classifying cancer subtypes than transcriptome profiling of an entire set of known protein-coding genes. miRNA profiling also allows classification of different stages in tumor progression and can predict disease outcome in some cases. Further characterization of these abnormal miRNA expression signatures and identification of the most significant and informative aberrantly expressed miRNAs could lead to the development of tissue- and biofluid-specific diagnostic markers, as well as a new type of oligonucleotide-based therapeutics. As researchers continue to study miRNA expression in cancer and focus on most relevant miRNAs, the further advancement of miRNA-detection technologies and bioinformatics algorithms is critical for successful identification of the most informative diagnostics markers among the tissue-specific miRNAs.

  14. Meaning in life for patients with cancer: validation of the Life Attitude Profile-Revised Scale.

    PubMed

    Erci, Behice

    2008-06-01

    This paper is a report of a study to adapt the Life Attitude Profile-Revised Scale for Turkish patients with cancer and to evaluate its psychometric properties. Cancer is a life-threatening illness that can challenge the experience of meaning in life. Meaning in life is a multidimensional concept involving meaning and purpose in life, as well as the motivation to find meaning and purpose in life. As meaning in life may be influenced by culture, a culture-sensitive tool is needed for its measurement. A convenience sample of 199 patients with cancer at a Turkish university hospital completed a structured questionnaire including demographic characteristics and the Life Attitude Profile-Revised Scale for Patients with Cancer in 2006. Item analysis, principal components analysis, internal consistency reliability and Cronbach's alpha were used to measure the psychometric properties of the items of the scale. In the assessment of construct validity, identified four factors with eigenvalues greater than 1 explained 46.91% of the total variance. Internal reliability coefficients of these four factor-based scales were 0.73 and 0.82 respectively. The present study provides evidence of the Life Attitude Profile-Revised Scale's validity, reliability and acceptability. This scale should be further evaluated with a larger sample, in different regions in Turkey and diverse populations of world. The scale has potential applications for use both in research and as a screening tool in clinical settings.

  15. Profiles of non-cancer diseases in atomic bomb survivors.

    PubMed

    Kodama, K; Fujiwara, S; Yamada, M; Kasagi, F; Shimizu, Y; Shigematsu, I

    1996-01-01

    This article summarizes the results of a recent study of atomic bomb radiation and non-cancer diseases in the AHS (Adult Health Study) population by the RERF (Radiation Effects Research Foundation) along with a general discussion of previous studies. The association of atomic bomb radiation and CVD was examined by incidence studies and prevalence studies of various endpoints of atherosclerosis, such as MI, stroke, aortic arch calcification, isolated systolic hypertension, and pulse wave velocity, and, although the excess was small, all endpoints indicated an increase of CVD in the heavily exposed group. Because of the consistency of the results, it is almost certain that CVD is higher among atomic bomb survivors. However, all CVD risk factors associated with lifestyle had not necessarily been adjusted for in studies to date, and it is difficult at present to conclude that the increase in CVD among survivors was a direct effect of radiation. Recent studies have demonstrated almost certainly that uterine myoma is more frequent among atomic bomb survivors. It cannot, at present, be concluded that uterine myoma is caused by radiation, because there are no reported studies of other exposed populations. Further analyses including the role of confounding factors as well as molecular approaches are needed to verify this radiation effect. The relationship between atomic bomb radiation exposure and hyperparathyroidism can now be said to have been established in view of the strong dose response, the agreement with results of studies of other populations, the high risk in the younger survivors, and the biological plausibility. Future studies by molecular approaches, etc., are needed to determine the pathogenic mechanism. Among other benign tumours, a dose response has been demonstrated for tumours of the thyroid, stomach and ovary. Although fewer studies have been conducted than for cancer, a clear association between radiation and various benign tumours is emerging

  16. A framework for personalized medicine: prediction of drug sensitivity in cancer by proteomic profiling

    PubMed Central

    2012-01-01

    Background The goal of personalized medicine is to provide patients optimal drug screening and treatment based on individual genomic or proteomic profiles. Reverse-Phase Protein Array (RPPA) technology offers proteomic information of cancer patients which may be directly related to drug sensitivity. For cancer patients with different drug sensitivity, the proteomic profiling reveals important pathophysiologic information which can be used to predict chemotherapy responses. Results The goal of this paper is to present a framework for personalized medicine using both RPPA and drug sensitivity (drug resistance or intolerance). In the proposed personalized medicine system, the prediction of drug sensitivity is obtained by a proposed augmented naive Bayesian classifier (ANBC) whose edges between attributes are augmented in the network structure of naive Bayesian classifier. For discriminative structure learning of ANBC, local classification rate (LCR) is used to score augmented edges, and greedy search algorithm is used to find the discriminative structure that maximizes classification rate (CR). Once a classifier is trained by RPPA and drug sensitivity using cancer patient samples, the classifier is able to predict the drug sensitivity given RPPA information from a patient. Conclusion In this paper we proposed a framework for personalized medicine where a patient is profiled by RPPA and drug sensitivity is predicted by ANBC and LCR. Experimental results with lung cancer data demonstrate that RPPA can be used to profile patients for drug sensitivity prediction by Bayesian network classifier, and the proposed ANBC for personalized cancer medicine achieves better prediction accuracy than naive Bayes classifier in small sample size data on average and outperforms other the state-of-the-art classifier methods in terms of classification accuracy. PMID:22759571

  17. [Sharing information of urological cancer patient in terminal stage using Cybozulive® for home medical care].

    PubMed

    Yumura, Yasushi; Hattori, Yusuke; Gobara, Ayako; Takamoto, Daiji; Yasuda, Kengo; Nakamura, Masafumi; Noguchi, Kazumi; Asahina, Kan; Kamijo, Takeo

    2014-09-01

    It is very important to share patient information because home patient care involves several different specialties of care. We introduced Cybozulive ® , a cloud-based free groupware, for 14 terminal-stage patients with urological cancer to share information among doctors and co-medical staff. This system enables access to patient information regardless of time and place. Of the 14 patients (mean age 74.4 years), 11 died of cancer. The average period in which Cybozulive® was used for the patients was 210 days. The average number of entries to the electronic bulletin board in this period was 88.4. We were able to obtain more information about the patients from the website. There was no difference in the average number of times that the patient consulted the out patient clinic before and after the introduction of Cybozulive® (before 7.0 ; after 6.3). After introduction of this system, eleven patients were hospitalized in our department 21 times. Eighteen of these 21 times, since we had acquired patient information from the website beforehand, there was a quick response for management of the emergency admission. This system could be used to construct a network for home care and may be helpful for sharing patient information in homecare.

  18. Proteomic profiling of the cancer microenvironment by antibody arrays.

    PubMed

    Knezevic, V; Leethanakul, C; Bichsel, V E; Worth, J M; Prabhu, V V; Gutkind, J S; Liotta, L A; Munson, P J; Petricoin, E F; Krizman, D B

    2001-10-01

    Critical changes in protein expression that enable tumors to initiate and progress originate in the local tissue microenvironment, and there are increasing indications that these microenvironmental alterations in protein expression play critical roles in shaping and directing this process. As a model to better understand how patterns of protein expression shape the tissue microenvironment, we analyzed protein expression in tissue derived from squamous cell carcinoma of the oral cavity through an antibody microarray approach for high-throughput proteomic analysis. Utilizing laser capture microdissection to procure total protein from specific microscopic cellular populations, we demonstrate that quantitative, and potentially qualitative, differences in expression patterns of multiple proteins within epithelial cells reproducibly correlate with oral cavity tumor progression. Furthermore, differential expression of multiple proteins was also found in stromal cells surrounding and adjacent to regions of diseased epithelium that directly correlated with tumor progression of the epithelium. Most of the proteins identified in both cell types are involved in signal transduction pathways, thus we hypothesize that extensive molecular communication involving complex cellular signaling between epithelium and stroma play a key role in driving oral cavity cancer progression.

  19. Gene expression profiling in vaccine therapy and immunotherapy for cancer

    PubMed Central

    Bedognetti, Davide; Wang, Ena; Sertoli, Mario Roberto; Marincola, Francesco M

    2012-01-01

    The identification of tumor antigens (TA) recognized by T cells led to the design of therapeutic strategies aimed at eliciting adaptive-immune responses. The last decade experience has shown that, although active immunization can induce enhancement of anti-cancer T cell precursors (easily detectable in standard assays), most often they are unable to induce tumor regression and, consequently, have scarce impact on overall survival. Moreover, in the few occasions when tumor rejection occurs, the mechanisms determining this phenomenon remain poorly understood, and data derived from in vivo human observations are rare. The advent of high-throughput gene expression analysis (microarrays) has cast new lights on unrecognized mechanisms that are now deemed as central for the development of an efficient immune-mediated tumor rejection. The aim of this article is to review the data about the molecular signature associated with this process. We believe that the description of how the mechanism of immune-mediated tissue destruction occurs would contribute to understand why it happens, thereby allowing to develop more effective immune-therapeutic strategies. PMID:20518712

  20. Molecular profiling of biliary tract cancer: a target rich disease

    PubMed Central

    Jain, Apurva

    2016-01-01

    Biliary tract cancers (BTCs) are relatively uncommon orphan tumors that have an aggressive disease course and a poor clinical outcome. Surgery is the only curative treatment, but most patients present with advanced disease and therefore have a limited survival. Gemcitabine and cisplatin based chemotherapy has been the only widely accepted standard systemic therapy regimen in these patients but these tumors can be chemoresistant, further complicating their management. In recent times, there has been considerable research in the genetics of BTC and with the advent of new, advanced technologies like next-generation sequencing (NGS) we are achieving a greater understanding of its disease biology. With the help of NGS, we have now been able to identify actionable mutations such as in the isocitrate dehydrogenase 1 (IDH1), FGFR2, BRAF and HER2/neu genes for targeted therapeutics and correlate the genetic variations with distinct clinical prognoses. This recent genetic information has the potential to make precision medicine a part of routine clinical practice for the management of BTC patients. PMID:27747093

  1. Mutational profiling of familial male breast cancers reveals similarities with luminal A female breast cancer with rare TP53 mutations.

    PubMed

    Deb, S; Wong, S Q; Li, J; Do, H; Weiss, J; Byrne, D; Chakrabarti, A; Bosma, T; Fellowes, A; Dobrovic, A; Fox, S B

    2014-12-09

    Male breast cancer (MBC) is still poorly understood with a large proportion arising in families with a history of breast cancer. Genomic studies have focused on germline determinants of MBC risk, with minimal knowledge of somatic changes in these cancers. Using a TruSeq amplicon cancer panel, this study evaluated 48 familial MBCs (3 BRCA1 germline mutant, 17 BRCA2 germline mutant and 28 BRCAX) for hotspot somatic mutations and copy number changes in 48 common cancer genes. Twelve missense mutations included nine PIK3CA mutations (seven in BRCAX patients), two TP53 mutations (both in BRCA2 patients) and one PTEN mutation. Common gains were seen in GNAS (34.1%) and losses were seen in GNAQ (36.4%), ABL1 (47.7%) and ATM (34.1%). Gains of HRAS (37.5% vs 3%, P=0.006), STK11 (25.0% vs 0%, P=0.01) and SMARCB1 (18.8% vs 0%, P=0.04) and the loss of RB1 (43.8% vs 13%, P=0.03) were specific to BRCA2 tumours. This study is the first to perform high-throughput somatic sequencing on familial MBCs. Overall, PIK3CA mutations are most commonly seen, with fewer TP53 and PTEN mutations, similar to the profile seen in luminal A female breast cancers. Differences in mutation profiles and patterns of gene gains/losses are seen between BRCA2 (associated with TP53/PTEN mutations, loss of RB1 and gain of HRAS, STK11 and SMARCB1) and BRCAX (associated with PIK3CA mutations) tumours, suggesting that BRCA2 and BRCAX MBCs may be distinct and arise from different tumour pathways. This has implications on potential therapies, depending on the BRCA status of MBC patients.

  2. Radiotherapy improves serum fatty acids and lipid profile in breast cancer.

    PubMed

    Shaikh, Sana; Channa, Naseem Aslam; Talpur, Farha Naz; Younis, Muhammad; Tabassum, Naila

    2017-05-18

    Breast cancer is a disease with diverse clinical symptoms, molecular profiles, and its nature to response its therapeutic treatments. Radiotherapy (RT), along with surgery and chemotherapy is a part of treatment in breast cancer. The aim of present study was to investigate pre and post treatment effects of radiotherapy in serum fatty acids and its lipids profile in patients with breast cancer. In this comparative as well as follow up study, Serum fatty acids were performed by gas chromatography to investigate fatty acids and Microlab for analysis of lipid profile. Among serum free and total fatty acids the major saturated fatty acids (SFAs) in serum lipids of breast cancer patients (pre and post treated) were stearic acid (18:0) and palmitic acid (16:0). These fatty acids contributed about 35-50% of total fatty acids. The decreased concentrations of linoleic acid (C18:2) and arachidonic acid (C20:4) with a lower ratio of C18:2/C18:1 was found in pretreated breast cancer patients as compared to controls. The n-3/n-6 ratio of breast cancer patients was decreased before treatment but it was 35% increased after treatment. In addition, plasma activity of D6 desaturase was increased in the breast cancer patients, while the activity of D5 desaturase was decreased. Increased levels of SFAs, monounsaturated fatty acids (MUFAs) and decreased polyunsaturated fatty acids (PUFAs) levels in breast cancer patients (pre and post treated) as compared to controls. Serum total cholesterol (TC) (224.4 mg/dL) and low density lipoprotein cholesterol (LDL-C) (142.9 mg/dL) were significantly increased in pretreated breast cancer patients but after the radiotherapy treatment, the TC (150.2 mg/dL) and LDL-C (89.8 mg/dL) were decreased. It seems that RT would have played a potential role in the treatment of BC. After RT the serum levels of PUFAs, TC, and LDL-C are improved. Our study reinforces the important role of RT in the management of BC. The level of PUFAs, TC, and LDL-C can be

  3. The potential role of comprehensive genomic profiling to guide targeted therapy for patients with biliary cancer.

    PubMed

    Lee, Hwajeong; Ross, Jeffrey S

    2017-06-01

    Remarkable advancements in techniques of genomic profiling and bioinformatics have led to the accumulation of vast amounts of knowledge on the genomic profiles of biliary tract cancer (BTC). Recent largescale molecular profiling studies have not only highlighted genomic differences characterizing tumors of the intrahepatic and extrahepatic bile ducts and gallbladder, but have also revealed differences in genomic profiles pertaining to associated risk factors. Novel genomic alterations such as FGFR2 fusions and IDH1/2 mutations in intrahepatic cholangiocarcinoma (ICC) and ERBB2 alterations in gallbladder cancer (GBCA) are emerging as targeted therapy options capable of advancing precision medicine for the care of these patients. Moreover, variable genomic alterations also appear to impact prognosis and overall disease outcome independent from their therapy selection value. High mutational burden and increased expression of immune checkpoint-related proteins observed in a subset of BTC also show a potential for guidance of immunotherapy. Thus, comprehensive genomic profiling (CGP) is rapidly achieving status as an integral component of precision medicine and is starting to become invaluable in guiding the management of patients with BTC, a rare disease with dismal outcome.

  4. Effects of culture media on metabolic profiling of the human gastric cancer cell line SGC7901.

    PubMed

    Huang, Zicheng; Shao, Wei; Gu, Jinping; Hu, Xiaomin; Shi, Yuanzhi; Xu, Wenqi; Huang, Caihua; Lin, Donghai

    2015-07-01

    Cell culture metabolomics has demonstrated significant advantages in cancer research. However, its applications have been impeded by some influencing factors such as culture media, which could significantly affect cellular metabolic profiles and lead to inaccuracy and unreliability of comparative metabolomic analysis of cells. To evaluate the effects of different culture media on cellular metabolic profiling, we performed NMR-based metabolomic analysis of the human gastric cancer cell line SGC7901 cultured in both RPMI1640 and DMEM. We found that SGC7901 cultured in the two media exhibited distinct metabolic profiles with obviously different levels of discrepant metabolites, even though they showed almost the same cellular morphology and proliferation rates. When SGC7901 originally cultured in RPMI1640 was gradually acclimated in DMEM, both the metabolic profiles and most of the discrepant metabolite levels gradually converged toward those of the cells originally cultured in DMEM without significantly altered cell proliferation rates. However, several metabolite levels did not show the converging trends. Our results indicate that the effects of culture media on metabolic profiling must be carefully taken into account for comparative metabolomic analysis of cell lines. This work may be of benefit to the development of cell culture metabolomics.

  5. Cancer mortality in Yukon 1999–2013: elevated mortality rates and a unique cancer profile

    PubMed Central

    Simkin, Jonathan; Woods, Ryan; Elliott, Catherine

    2017-01-01

    ABSTRACT Background: Although cancer is the leading cause of death in Canada, cancer in the North has been incompletely described. Objective: To determine cancer mortality rates in the Yukon Territory, compare them with Canadian rates, and identify major causes of cancer mortality. Design: The Yukon Vital Statistics Registry provided all cancer deaths for Yukon residents between 1999-2013. Age-standardised mortality rates (ASMRs) were calculated using direct standardisation and compared with Canadian rates. Standardised mortality ratios (SMRs) were calculated using indirect standardisation relative to age-specific rates from Canada, British Columbia (BC), and three sub-provincial BC administrative health regions : Interior Health (IH), Northern Health (NH) and Vancouver Coastal Health (VCH). Trends in smoothed ASMRs were examined with graphical methods. Results: Yukon’s all-cancer ASMRs were elevated compared with national and provincial rates for the entire period. Disparities were greatest compared with the urban VCH: prostate (SMRVCH=246.3, 95% CI 140.9–351.6), female lung (SMRVCH=221.2, 95% CI 154.3–288.1), female breast (SMRVCH=169.0 95% CI, 101.4–236.7), and total colorectal (SMRVCH=149.3, 95% CI 101.8–196.8) cancers were significantly elevated. Total stomach cancer mortality was significantly elevated compared with all comparators. Conclusions: Yukon cancer mortality rates were elevated compared with national, provincial, urban, and southern-rural jurisdictions. More research is required to elucidate these differences. PMID:28598269

  6. Home Literacy Environment Profiles of Children with Language Impairment: Associations with Caregiver- and Child-Specific Factors

    ERIC Educational Resources Information Center

    Tambyraja, Sherine R.; Schmitt, Mary Beth; Farquharson, Kelly; Justice, Laura M.

    2017-01-01

    Background: Numerous studies suggest a positive relationship between the home literacy environment (HLE) and children's language and literacy skills, yet very little research has focused on the HLE of children with language impairment (LI). Children with LI are at risk for reading difficulties; thus, understanding the nature and frequency of their…

  7. Global metabolite profiling of human colorectal cancer xenografts in mice using HPLC-MS/MS.

    PubMed

    Loftus, Neil J; Lai, Lindsay; Wilkinson, Robert W; Odedra, Rajesh; Wilson, Ian D; Barnes, Alan J

    2013-06-07

    Reversed-phase gradient LC-MS was used to perform untargeted metabonomic analysis on extracts of human colorectal cancer (CRC) cell lines (COLO 205, HT-29, HCT 116 and SW620) subcutaneously implanted into age-matched athymic nude male mice to study small molecule metabolic profiles and examine possible correlations with human cancer biopsies. Following high mass accuracy data analysis using MS and MS/MS, metabolites were identified by searching against major metabolite databases including METLIN, MASSBANK, The Human Metabolome Database, PubChem, Biospider, LipidMaps and KEGG. HT-29 and COLO 205 tumor xenografts showed a distribution of metabolites that differed from SW620 and HCT 116 xenografts (predominantly on the basis of relative differences in the amounts of amino acids and lipids detected). This finding is consistent with NMR-based analysis of human colorectal tissue, where the metabolite profiles of HT-29 tumors exhibit the greatest similarity to human rectal cancer tissue with respect to changes in the relative amounts of lipids and choline-containing compounds. As the metabolic signatures of cancer cells result from oncogene-directed metabolic reprogramming, the HT-29 xenografts in mice may prove to be a useful model to further study the tumor microenvironment and cancer biology.

  8. Genome-wide transcript profiling reveals novel breast cancer-associated intronic sense RNAs.

    PubMed

    Kim, Sang Woo; Fishilevich, Elane; Arango-Argoty, Gustavo; Lin, Yuefeng; Liu, Guodong; Li, Zhihua; Monaghan, A Paula; Nichols, Mark; John, Bino

    2015-01-01

    Non-coding RNAs (ncRNAs) play major roles in development and cancer progression. To identify novel ncRNAs that may identify key pathways in breast cancer development, we performed high-throughput transcript profiling of tumor and normal matched-pair tissue samples. Initial transcriptome profiling using high-density genome-wide tiling arrays revealed changes in over 200 novel candidate genomic regions that map to intronic regions. Sixteen genomic loci were identified that map to the long introns of five key protein-coding genes, CRIM1, EPAS1, ZEB2, RBMS1, and RFX2. Consistent with the known role of the tumor suppressor ZEB2 in the cancer-associated epithelial to mesenchymal transition (EMT), in situ hybridization reveals that the intronic regions deriving from ZEB2 as well as those from RFX2 and EPAS1 are down-regulated in cells of epithelial morphology, suggesting that these regions may be important for maintaining normal epithelial cell morphology. Paired-end deep sequencing analysis reveals a large number of distinct genomic clusters with no coding potential within the introns of these genes. These novel transcripts are only transcribed from the coding strand. A comprehensive search for breast cancer associated genes reveals enrichment for transcribed intronic regions from these loci, pointing to an underappreciated role of introns or mechanisms relating to their biology in EMT and breast cancer.

  9. Genome-Wide Transcript Profiling Reveals Novel Breast Cancer-Associated Intronic Sense RNAs

    PubMed Central

    Lin, Yuefeng; Liu, Guodong; Li, Zhihua; Monaghan, A. Paula; Nichols, Mark; John, Bino

    2015-01-01

    Non-coding RNAs (ncRNAs) play major roles in development and cancer progression. To identify novel ncRNAs that may identify key pathways in breast cancer development, we performed high-throughput transcript profiling of tumor and normal matched-pair tissue samples. Initial transcriptome profiling using high-density genome-wide tiling arrays revealed changes in over 200 novel candidate genomic regions that map to intronic regions. Sixteen genomic loci were identified that map to the long introns of five key protein-coding genes, CRIM1, EPAS1, ZEB2, RBMS1, and RFX2. Consistent with the known role of the tumor suppressor ZEB2 in the cancer-associated epithelial to mesenchymal transition (EMT), in situ hybridization reveals that the intronic regions deriving from ZEB2 as well as those from RFX2 and EPAS1 are down-regulated in cells of epithelial morphology, suggesting that these regions may be important for maintaining normal epithelial cell morphology. Paired-end deep sequencing analysis reveals a large number of distinct genomic clusters with no coding potential within the introns of these genes. These novel transcripts are only transcribed from the coding strand. A comprehensive search for breast cancer associated genes reveals enrichment for transcribed intronic regions from these loci, pointing to an underappreciated role of introns or mechanisms relating to their biology in EMT and breast cancer. PMID:25798919

  10. Carcinoma of unknown primary with a colon-cancer profile-changing paradigm and emerging definitions.

    PubMed

    Varadhachary, Gauri R; Raber, Martin N; Matamoros, Aurelio; Abbruzzese, James L

    2008-06-01

    Carcinoma of unknown primary (CUP), which accounts for about 3-5% of all new cancers, is a challenging heterogeneous entity with an unmet research need. Traditionally, CUP has been managed with broad-spectrum chemotherapy, but with the increasing availability of sophisticated diagnostic techniques and the emergence of new treatments that have been shown to be effective in specific cancers the one-treatment-fits-all approach to CUP might eventually no longer be valid. CUP in association with a colon-cancer profile (CCP-CUP) is an example of an emerging, specific CUP subset that seems to benefit from a tailored approach. CCP-CUP is identified by CK20 and CDX2-positive and CK7-negative immunohistochemistry and a clinical course consistent with that of patients known to have metastatic colon cancer. Our findings suggest that patients with CCP-CUP derive substantial benefit from the use of specific treatments developed for colon cancer and larger clinical trials are warranted to more definitely test this finding. In the era of molecular profiling, we expect that additional work with CCP-CUP and other CUP subsets will provide attractive tailored treatment alternatives, with efficacies that exceed the current one-treatment-fits-all approach.

  11. Mass Spectrometry-Based Metabolomics Identifies Longitudinal Urinary Metabolite Profiles Predictive of Radiation-Induced Cancer.

    PubMed

    Cook, John A; Chandramouli, Gadisetti V R; Anver, Miriam R; Sowers, Anastasia L; Thetford, Angela; Krausz, Kristopher W; Gonzalez, Frank J; Mitchell, James B; Patterson, Andrew D

    2016-03-15

    Nonlethal exposure to ionizing radiation (IR) is a public concern due to its known carcinogenic effects. Although latency periods for IR-induced neoplasms are relatively long, the ability to detect cancer as early as possible is highly advantageous for effective therapeutic intervention. Therefore, we hypothesized that metabolites in the urine from mice exposed to total body radiation (TBI) would predict for the presence of cancer before a palpable mass was detected. In this study, we exposed mice to 0 or 5.4 Gy TBI, collected urine samples periodically over 1 year, and assayed urine metabolites by using mass spectrometry. Longitudinal data analysis within the first year post-TBI revealed that cancers, including hematopoietic, solid, and benign neoplasms, could be distinguished by unique urinary signatures as early as 3 months post-TBI. Furthermore, a distinction among different types of malignancies could be clearly delineated as early as 3 months post-TBI for hematopoietic neoplasms, 6 months for solid neoplasms, and by 1 year for benign neoplasms. Moreover, the feature profile for radiation-exposed mice 6 months post-TBI was found to be similar to nonirradiated control mice at 18 months, suggesting that TBI accelerates aging. These results demonstrate that urine feature profiles following TBI can identify cancers in mice prior to macroscopic detection, with important implications for the early diagnosis and treatment. ©2016 American Association for Cancer Research.

  12. Clinical and epidemiological profile of cases of deaths from stomach cancer in the National Cancer Institute, Brazil

    PubMed Central

    Guedes, Maria Teresa dos Santos; de Jesus, José Paulo; de Souza Filho, Odilon; Fontenele, Raquel Malta; Sousa, Ana Inês

    2014-01-01

    Introduction Stomach cancer is the third most common cause of death worldwide, mainly affecting people with low socioeconomic status. In Brazil, we expect 20,390 new cases of stomach cancer in 2014, in both sexes, and according to the proportional distribution of the ten most prevalent types of cancer (except non-melanoma skin cancer) expected for 2014, this type of cancer was estimated to be the fourth most common in men and sixth in women. Aim To investigate and analyse the clinical and epidemiological profile of deaths caused by stomach adenocarcinoma in patients enrolled in the National Cancer Institute, Brazil. Methods Cross-sectional study, with samples which consisted of data from the medical records of deaths from stomach cancer, enrolled in the period from 1 February 2009 to 31 March 2012 and who had died as of 30 April 2012. Statistical Analysis Used The Epi Info ®, version 7 Results We included 264 cases, mostly male. The mean age was 61.7 years. They were smokers, drinkers, white, and married, with elementary education and an income of one minimum salary. They had advanced stage disease (E IV), with symptoms characteristic of this phase, and the majority died within six months. Conclusion The findings are similar to other studies. The advanced stage of the disease at the time of admission of the patients reflects the difficulty for users of the Unified Health System to access early diagnosis, demonstrating the need for efforts to identify groups and risk factors for the development of gastric cancer. Training of health professionals will facilitate planning and implementation of programmes for the prevention and control of disease, considering socioeconomic conditions, as seen in the sample, which is common among most users. PMID:25114717

  13. Expanded metabolomics approach to profiling endogenous carbohydrates in the serum of ovarian cancer patients.

    PubMed

    Cheng, Yu; Li, Li; Zhu, Bangjie; Liu, Feng; Wang, Yan; Gu, Xue; Yan, Chao

    2016-01-01

    We applied hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry to the quantitative analysis of serum from 58 women, including ovarian cancer patients, ovarian benign tumor patients, and healthy controls. All of these ovarian cancer and ovarian benign tumor patients have elevated cancer antigen 125, which makes them clinically difficult to differentiate the malignant from the benign. All of the 16 endogenous carbohydrates were quantitatively detected in the human sera, of which, eight endogenous carbohydrates were significantly different (P-value < 0.05) between the ovarian cancer and healthy control. According to the receiver operating characteristic curve analysis, arabitol was the most potentially specific biomarker for discriminating ovarian cancer from healthy control, having an area under the curve of 0.911. A panel of metabolite markers composed of maltose, maltotriose, raffinose, and mannitol was selected, which was able to discriminate the ovarian cancer from the benign ovarian tumor counterparts, with an area under concentration-time curve value of 0.832. Endogenous carbohydrates in the expanded metabolomics approach after the global metabolic profiling are characterized and are potential biomarkers for the early diagnosis of ovarian cancer.

  14. Identification of CD200+ colorectal cancer stem cells and their gene expression profile.

    PubMed

    Zhang, Shan-Shan; Huang, Zai-Wei; Li, Li-Xuan; Fu, Jin-Jin; Xiao, Bing

    2016-10-01

    CD200 is a cell surface glycoprotein that has been implicated in a variety of human cancer cells. It has been proposed as a cancer stem cell (CSC) marker in colon cancer and is closely related to tumor immunosuppression. However, there is little functional data supporting its role as a true CSC marker, and the mechanism by which CD200 contributes to colorectal cancer has not been elucidated. In the present study, CD200+ and CD200- COLO 205 colorectal cancer cells were sorted out by flow cytometry, and colonosphere formation and Transwell migration assays were performed. Affymetrix Human U133 Plus2.0 arrays were used to screen the gene expression profiles of CD200+ and CD200- colorectal cancer cells. The results suggest that there are differentially expressed genes between the two subpopulations, including several important genes that function in cell proliferation, metastasis, apoptosis and the immune response. Pathway analysis revealed that the Wnt, MAPK and calcium signaling pathways were differentially expressed between CD200+ and CD200- cells. Moreover, several key genes upregulated in CD200+ cells were also highly overexpressed in CD44+CD133+ colorectal stem cells compared to the CD44-CD133- fraction of the same cell line. In the present study, we showed for the first time a correlation between CD200 expression and the Wnt signaling pathway in colon cancer cells.

  15. Factors influencing the opioid response in advanced cancer patients with pain followed at home: the effects of age and gender.

    PubMed

    Mercadante, S; Casuccio, A; Pumo, S; Fulfaro, F

    2000-03-01

    The aim of this study was to evaluate the influence of age and gender on pain characteristics and opioid response in advanced cancer patients followed at home. A perspective study was carried out in a sample of 181 consecutive advanced cancer patients who required opioids in the last 4 weeks before death. Pain intensity and symptoms associated with opioid therapy at weekly intervals for 4 weeks were recorded, as were the previous oncological treatments. Opioid doses increased over time, but remained stable in the last 2 weeks of life, while pain intensity decreased over time despite unchanged use of NSAIDs. A considerable increase in symptom intensity was observed in the last weeks of life, except for nausea and vomiting. Visceral pain was more often reported in women. Male patients more often presented somatic pain mechanisms. Neuropathic pain was associated with higher mean VAS intensity and was equally reported in male and female patients and in the different age groups. Very old patients, who received less chemotherapy, required less opioid doses and reported a lower intensity of some symptoms, while reporting similar pain relief. Dry mouth was more frequent in adults than in very old patients. The identification of specific factors and pain characteristics may be useful in suggesting the likelihood of response in terms of analgesia and opioid-related adverse effects. Age and gender analysis should be included in all cancer pain and symptom control studies, as they may have an influence on cancer pain prognosis.

  16. From drug response profiling to target addiction scoring in cancer cell models.

    PubMed

    Yadav, Bhagwan; Gopalacharyulu, Peddinti; Pemovska, Tea; Khan, Suleiman A; Szwajda, Agnieszka; Tang, Jing; Wennerberg, Krister; Aittokallio, Tero

    2015-10-01

    Deconvoluting the molecular target signals behind observed drug response phenotypes is an important part of phenotype-based drug discovery and repurposing efforts. We demonstrate here how our network-based deconvolution approach, named target addiction score (TAS), provides insights into the functional importance of druggable protein targets in cell-based drug sensitivity testing experiments. Using cancer cell line profiling data sets, we constructed a functional classification across 107 cancer cell models, based on their common and unique target addiction signatures. The pan-cancer addiction correlations could not be explained by the tissue of origin, and only correlated in part with molecular and genomic signatures of the heterogeneous cancer cells. The TAS-based cancer cell classification was also shown to be robust to drug response data resampling, as well as predictive of the transcriptomic patterns in an independent set of cancer cells that shared similar addiction signatures with the 107 cancers. The critical protein targets identified by the integrated approach were also shown to have clinically relevant mutation frequencies in patients with various cancer subtypes, including not only well-established pan-cancer genes, such as PTEN tumor suppressor, but also a number of targets that are less frequently mutated in specific cancer types, including ABL1 oncoprotein in acute myeloid leukemia. An application to leukemia patient primary cell models demonstrated how the target deconvolution approach offers functional insights into patient-specific addiction patterns, such as those indicative of their receptor-type tyrosine-protein kinase FLT3 internal tandem duplication (FLT3-ITD) status and co-addiction partners, which may lead to clinically actionable, personalized drug treatment developments. To promote its application to the future drug testing studies, we have made available an open-source implementation of the TAS calculation in the form of a stand-alone R

  17. Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression.

    PubMed

    Chen, Huanhuan; Deng, Zaian; Huang, Chuncui; Wu, Hongmei; Zhao, Xia; Li, Yan

    2017-07-01

    Aberrant changes of N-glycan modifications on proteins have been linked to various diseases including different cancers, suggesting possible avenue for exploring their etiologies based on N-glycomic analysis. Changes in N-glycan patterns during epithelial ovarian cancer development have so far been investigated mainly using serum, plasma, ascites, and cell lines. However, changes in patterns of N-glycans in tumor tissues during epithelial ovarian cancer progression have remained largely undefined. To investigate whether changes in N-glycan patterns correlate with oncogenesis and progression of epithelial ovarian cancer, we profiled N-glycans from formalin-fixed paraffin-embedded tissue slides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and quantitatively compared among different pathological grades of epithelial ovarian cancer and healthy controls. Our results show that among the 80 compositions of N-glycan detected, expression levels of high-mannose type were higher in epithelial ovarian cancer samples than that observed in healthy controls, accompanied by reduced levels of hybrid-type glycans. By applying receiver operating characteristic analysis, we show that a combined panel composed of four high-mannose and three fucosylated neutral complex N-glycans allows for good discrimination of epithelial ovarian cancer from healthy controls. Furthermore, using a statistical analysis of variance assay, we found that different N-glycan patterns, including 2 high-mannose-type, 2 fucosylated and sialylated complex structures, and 10 fucosylated neutral complex N-glycans, exhibited specific changes in N-glycan abundance across epithelial ovarian cancer grades. Together, our results provide strong evidence that N-glycomic changes are a strong indicator for epithelial ovarian cancer pathological grades and should provide avenues to identify novel biomarkers for epithelial ovarian cancer diagnosis and monitoring.

  18. Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression

    PubMed Central

    Rhodes, Daniel R.; Yu, Jianjun; Shanker, K.; Deshpande, Nandan; Varambally, Radhika; Ghosh, Debashis; Barrette, Terrence; Pandey, Akhilesh; Chinnaiyan, Arul M.

    2004-01-01

    Many studies have used DNA microarrays to identify the gene expression signatures of human cancer, yet the critical features of these often unmanageably large signatures remain elusive. To address this, we developed a statistical method, comparative metaprofiling, which identifies and assesses the intersection of multiple gene expression signatures from a diverse collection of microarray data sets. We collected and analyzed 40 published cancer microarray data sets, comprising 38 million gene expression measurements from >3,700 cancer samples. From this, we characterized a common transcriptional profile that is universally activated in most cancer types relative to the normal tissues from which they arose, likely reflecting essential transcriptional features of neoplastic transformation. In addition, we characterized a transcriptional profile that is commonly activated in various types of undifferentiated cancer, suggesting common molecular mechanisms by which cancer cells progress and avoid differentiation. Finally, we validated these transcriptional profiles on independent data sets. PMID:15184677

  19. Home parenteral nutrition improves quality of life and nutritional status in patients with cancer: a French observational multicentre study.

    PubMed

    Culine, S; Chambrier, C; Tadmouri, A; Senesse, P; Seys, P; Radji, A; Rotarski, M; Balian, A; Dufour, P

    2014-07-01

    Malnutrition is a predictor of poor outcomes in patients with cancer. Little is known about the benefit of nutritional support in these patients. The purpose of this study was to assess the impact of home parenteral nutrition (HPN) on quality of life (Qol) in cancer patients. We performed an observational prospective study to determine the impact of HPN on Qol in a population of patients with heterogeneous cancer. Physicians, patients and family members had to complete a questionnaire before HPN administration and 28 days after the course of HPN. Qol was evaluated using the self-administered questionnaire FACT-G. We included 767 patients with cancer of whom 437 ended the study. Mean patient age was 63±11.4 years and 60.5% were men. Primary gastrointestinal cancer was reported in 50% of patients and 65.3% were presenting metastases. Malnutrition was reported in 98.3%. After 28 days of HPN intake, significant improvement was observed in the Qol (49.95±5.82 vs. 48.35±5.01 at baseline, p<0.0001). The mean weight, serum albumin and the nutrition risk index had also improved significantly. Most patients (78%) had perceived a positive impact of the HPN. A significant improvement in patient's well-being was perceived also by family members and physicians. Our data suggest that preventing and correcting malnutrition using HPN in patients with cancer might have a significant benefit on their well-being. Randomized controlled studies are required to confirm this finding.

  20. Home kitchen ventilation, cooking fuels, and lung cancer risk in a prospective cohort of never smoking women in Shanghai, China.

    PubMed

    Kim, Christopher; Gao, Yu-Tang; Xiang, Yong-Bing; Barone-Adesi, Francesco; Zhang, Yawei; Hosgood, H Dean; Ma, Shuangge; Shu, Xiao-ou; Ji, Bu-Tian; Chow, Wong-Ho; Seow, Wei Jie; Bassig, Bryan; Cai, Qiuyin; Zheng, Wei; Rothman, Nathaniel; Lan, Qing

    2015-02-01

    Indoor air pollution (IAP) caused by cooking has been associated with lung cancer risk in retrospective case-control studies in developing and rural countries. We report the association of cooking conditions, fuel use, oil use, and risk of lung cancer in a developed urban population in a prospective cohort of women in Shanghai. A total of 71,320 never smoking women were followed from 1996 through 2009 and 429 incident lung cancer cases were identified. Questionnaires collected information on household living and cooking practices for the three most recent residences and utilization of cooking fuel and oil, and ventilation conditions. Cox proportional hazards regression estimated the association for kitchen ventilation conditions, cooking fuels, and use of cooking oils for the risk of lung cancer by hazard ratios (HR) with 95% confidence intervals (95% CI). Ever poor kitchen ventilation was associated with a 49% increase in lung cancer risk (HR: 1.49; 95% CI: 1.15-1.95) compared to never poor ventilation. Ever use of coal was not significantly associated. However, ever coal use with poor ventilation (HR: 1.69; 95% CI: 1.22-2.35) and 20 or more years of using coal with poor ventilation (HR: 2.03; 95% CI: 1.35-3.05) was significantly associated compared to no exposure to coal or poor ventilation. Cooking oil use was not significantly associated. These results demonstrate that IAP from poor ventilation of coal combustion increases the risk of lung cancer and is an important public health issue in cities across China where people may have lived in homes with inadequate kitchen ventilation. © 2014 UICC.

  1. Home kitchen ventilation, cooking fuels, and lung cancer risk in a prospective cohort of never smoking women in Shanghai, China

    PubMed Central

    Kim, Christopher; Gao, Yu-Tang; Xiang, Yong-Bing; Barone-Adesi, Francesco; Zhang, Yawei; Hosgood, H. Dean; Ma, Shuangge; Shu, Xiao-ou; Ji, Bu-Tian; Chow, Wong-Ho; Seow, Wei Jie; Bassig, Bryan; Cai, Qiuyin; Zheng, Wei; Rothman, Nathaniel; Lan, Qing

    2014-01-01

    Indoor air pollution (IAP) caused by cooking has been associated with lung cancer risk in retrospective case-control studies in developing and rural countries. We report the association of cooking conditions, fuel use, oil use and risk of lung cancer in a developed urban population in a prospective cohort of women in Shanghai. A total of 71,320 never smoking women were followed from 1996 through 2009 and 429 incident lung cancer cases were identified. Questionnaires collected information on household living and cooking practices for the women’s three most recent residences and utilization of cooking fuel and oil, and ventilation conditions. Cox proportional hazards regression estimated the association for kitchen ventilation conditions, cooking fuels, and use of cooking oils for the risk of lung cancer by hazard ratios (HR) with 95% confidence intervals (95% CI). Ever poor kitchen ventilation was associated with a 49% increase in lung cancer risk (HR: 1.49; 95% CI: 1.15–1.95) compared to never poor ventilation. Ever use of coal was not significantly associated. However, ever coal use with poor ventilation (HR: 1.69; 95% CI: 1.22–2.35) and twenty or more years of using coal (HR: 2.03; 95% CI: 1.35–3.05) was significantly associated compared to no exposure to coal or poor ventilation. Cooking oil use was not significantly associated. These results demonstrate that IAP from poor ventilation of coal combustion increases the risk of lung cancer and is an important public health issue in cities across China where people may have lived in homes with inadequate kitchen ventilation. PMID:24917360

  2. Identification of microRNA profile specific to cancer stem-like cells directly isolated from human larynx cancer specimens.

    PubMed

    Karatas, Omer Faruk; Suer, Ilknur; Yuceturk, Betul; Yilmaz, Mehmet; Oz, Buge; Guven, Gulgun; Cansiz, Harun; Creighton, Chad J; Ittmann, Michael; Ozen, Mustafa

    2016-11-05

    Emerging evidences proposed that microRNAs are associated with regulation of distinct physio-pathological processes including development of normal stem cells and carcinogenesis. In this study we aimed to investigate microRNA profile of cancer stem-like cells (CSLCs) isolated form freshly resected larynx cancer (LCa) tissue samples. CD133 positive (CD133(+)) stem-like cells were isolated from freshly resected LCa tumor specimens. MicroRNA profile of 12 pair of CD133(+) and CD133(-) cells was determined using microRNA microarray and differential expressions of selvected microRNAs were validated by quantitative real time PCR (qRT-PCR). MicroRNA profiling of CD133(+) and CD133(-) LCa samples with microarray revealed that miR-26b, miR-203, miR-200c, and miR-363-3p were significantly downregulated and miR-1825 was upregulated in CD133(+) larynx CSLCs. qRT-PCR analysis in a total of 25 CD133(+)/CD133(-) sample pairs confirmed the altered expressions of these five microRNAs. Expressions of miR-26b, miR-200c, and miR-203 were significantly correlated with miR-363-3p, miR-203, and miR-363-3p expressions, respectively. Furthermore, in silico analysis revealed that these microRNAs target both cancer and stem-cell associated signaling pathways. Our results showed that certain microRNAs in CD133(+) cells could be used as cancer stem cell markers. Based on these results, we propose that this panel of microRNAs might carry crucial roles in LCa pathogenesis through regulating stem cell properties of tumor cells.

  3. Metabolomic profile in pancreatic cancer patients: a consensus-based approach to identify highly discriminating metabolites

    PubMed Central

    Di Gangi, Iole Maria; Mazza, Tommaso; Fontana, Andrea; Copetti, Massimiliano; Fusilli, Caterina; Ippolito, Antonio; Mattivi, Fulvio; Latiano, Anna; Andriulli, Angelo

    2016-01-01

    Purpose pancreatic adenocarcinoma is the fourth leading cause of cancer related deaths due to its aggressive behavior and poor clinical outcome. There is a considerable variability in the frequency of serum tumor markers in cancer' patients. We performed a metabolomics screening in patients diagnosed with pancreatic cancer. Experimental Design Two targeted metabolomic assays were conducted on 40 serum samples of patients diagnosed with pancreatic cancer and 40 healthy controls. Multivariate methods and classification trees were performed. Materials and Methods Sparse partial least squares discriminant analysis (SPLS-DA) was used to reduce the high dimensionality of a pancreatic cancer metabolomic dataset, differentiating between pancreatic cancer (PC) patients and healthy subjects. Using Random Forest analysis palmitic acid, 1,2-dioleoyl-sn-glycero-3-phospho-rac-glycerol, lanosterol, lignoceric acid, 1-monooleoyl-rac-glycerol, cholesterol 5α,6α epoxide, erucic acid and taurolithocholic acid (T-LCA), oleoyl-L-carnitine, oleanolic acid were identified among 206 metabolites as highly discriminating between disease states. Comparison between Receiver Operating Characteristic (ROC) curves for palmitic acid and CA 19-9 showed that the area under the ROC curve (AUC) of palmitic acid (AUC=1.000; 95% confidence interval) is significantly higher than CA 19-9 (AUC=0.963; 95% confidence interval: 0.896-1.000). Conclusion Mass spectrometry-based metabolomic profiling of sera from pancreatic cancer patients and normal subjects showed significant alterations in the profiles of the metabolome of PC patients as compared to controls. These findings offer an information-rich matrix for discovering novel candidate biomarkers with diagnostic or prognostic potentials. PMID:26735340

  4. A DNA hypermethylation profile reveals new potential biomarkers for prostate cancer diagnosis and prognosis.

    PubMed

    Ashour, Nadia; Angulo, Javier C; Andrés, Guillermo; Alelú, Raúl; González-Corpas, Ana; Toledo, María V; Rodríguez-Barbero, José M; López, Jose I; Sánchez-Chapado, Manuel; Ropero, Santiago

    2014-09-01

    DNA hypermethylation has emerged as a novel molecular biomarker for the evaluation of prostate cancer diagnosis and prognosis. Defining the specific gene hypermethylation profile for prostate cancer could involve groups of genes that specifically discriminate patients with indolent and aggressive tumors. Genome-wide methylation analysis was performed on 83 tumor and 10 normal prostate samples using the GoldenGate Methylation Cancer Panel I (Illumina, Inc.). All clinical stages of disease were considered. We found 41 genes hypermethylated in more than 20% of the tumors analyzed (P < 0.01). Of these, we newly identified GSTM2 and PENK as being genes that are hypermethylated in prostate cancer and that were simultaneously methylated in 40.9% of the tumors analyzed. We also identified panels of genes that are more frequently methylated in tumor samples with clinico-pathological indicators of poor prognosis: a high Gleason score, elevated Ki-67, and advanced disease. Of these, we found simultaneous hypermethylation of CFTR and HTR1B to be common in patients with a high Gleason score and high Ki-67 levels; this might indicate the population at higher risk of therapeutic failure. The DNA hypermethylation profile was associated with cancer-specific mortality (log-rank test, P = 0.007) and biochemical recurrence-free survival (log-rank test, P = 0.0008). Our findings strongly indicate that epigenetic silencing of GSTM2 and PENK is a common event in prostate cancer that could be used as a molecular marker for prostate cancer diagnosis. In addition, simultaneous HTR1B and CFTR hypermethylation could help discriminate aggressive from indolent prostate tumors. © 2014 Wiley Periodicals, Inc.

  5. Estrogen and progesterone receptor status affect genome-wide DNA methylation profile in breast cancer.

    PubMed

    Li, Lian; Lee, Kyoung-Mu; Han, Wonshik; Choi, Ji-Yeob; Lee, Ji-Young; Kang, Gyeong Hoon; Park, Sue Kyung; Noh, Dong-Young; Yoo, Keun-Young; Kang, Daehee

    2010-11-01

    DNA methylation is the main epigenetic modification that occurs at the early stages of carcinogenesis. We performed a genome-wide DNA methylation profiling to evaluate whether the DNA methylation state is different in the estrogen receptor (ER) and progesterone receptor (PR) status of breast cancer. Twelve ER+/PR+ and 12 ER-/PR- breast cancer tissues were selected from the biorepository of the Seoul Breast Cancer Study for Infinium Methylation Assay. The difference of the DNA methylation state of 27 578 methylation sites in 14 000 genes between two groups was evaluated by Student's t-test. False discovery rate (FDR) was estimated to evaluate the probability of false positive associations. Of the 27 578 sites, 148 sites (0.54%) were significantly different between ER+/PR+ and ER-/PR- breast cancers (P < 0.001); 93 hypermethylated and 55 hypomethylated. Five genes, FAM124B (P = 7.26 × 10(-7)), MANEAL (P = 3.38 × 10(-7)), ST6GALNAC1 (P = 2.85 × 10(-6)), NAV1 (P = 5.94 × 10(-6)) and PER1 (P = 6.45 × 10(-6)) remained significant after correction for multiple tests (FDR < 0.05). In a subsequent replication study for five genes, four of the five genes were validated; FAM124B and ST6GALNAC1 were significantly hypermethylated, and NAV1 and PER1 were significantly hypomethylated in ER+/PR+ breast cancers (P < 0.05). In the first genome-wide DNA methylation profiling according to the receptor status of breast cancer, we found that ER/PR status affects the DNA methylation state of FAM124B, ST6GALNAC1, NAV1 and PER1 in breast cancer.

  6. Profiling analysis of circulating microRNA expression in cervical cancer.

    PubMed

    Nagamitsu, Yuzo; Nishi, Hirotaka; Sasaki, Toru; Takaesu, Yotaro; Terauchi, Fumitoshi; Isaka, Keiichi

    2016-07-01

    MicroRNA (miRNA) expression is altered in cancer cells and is associated with the development and progression of various types of cancer. Accordingly, miRNAs may serve as diagnostic or prognostic biomarkers in cancer patients. In this study, we attempted to analyze circulating exosomal miRNA in patients with cervical cancer. Total RNA was extracted from the serum of healthy subjects, subjects with cervical intraepithelial neoplasia (CIN) and patients with cervical cancer. We first investigated miRNA expression profiles in 6 serum samples from healthy subjects and patients with cervical cancer using the miRCURY LNA microRNA array. miRNAs with significant differences in expression were validated in a larger sample set by quantitative reverse transcription-polymerase chain reaction, using TaqMan gene expression assays. The results of the miRCURY LNA microRNA array indicated that 6 of 1,223 miRNAs found in serum samples from cervical cancer patients and normal controls exhibited a >3.0-fold change in expression level in subjects with cervical cancer, with a P-value of <0.01. In a validation set (n=131) that investigated the expression of 4 of the 6 miRNAs (miR-483-5p, miR-1246, miR-1275 and miR-1290), miR-1290 was found to have significantly higher expression levels in cervical cancer samples (n=45) compared with control samples (n=31). We also found that the median levels of these miRNAs were significantly higher in subjects with cervical cancer (n=45) compared with those in subjects with CIN (n=55). Circulating miRNAs were not correlated with clinicopathological parameters. However, receiver operating characteristic curve analysis suggested that these serum miRNAs may be useful diagnostic markers in cervical cancer. The expression of circulating miR-1290 was significantly higher in the blood of cervical cancer patients compared with that in controls and may thus serve as a useful biomarker in cervical cancer diagnosis. However, larger studies are required to fully

  7. Profiles.

    ERIC Educational Resources Information Center

    School Arts, 1979

    1979-01-01

    Profiles seven Black, Native American, and Chicano artists and art teachers: Hale A. Woodruff, Allan Houser, Luis Jimenez, Betrand D. Phillips, James E. Pate, I, and Fernando Navarro. This article is part of a theme issue on multicultural art. (SJL)

  8. Profiles.

    ERIC Educational Resources Information Center

    School Arts, 1979

    1979-01-01

    Profiles seven Black, Native American, and Chicano artists and art teachers: Hale A. Woodruff, Allan Houser, Luis Jimenez, Betrand D. Phillips, James E. Pate, I, and Fernando Navarro. This article is part of a theme issue on multicultural art. (SJL)

  9. Metabolomic profiling for the identification of novel diagnostic markers in prostate cancer.

    PubMed

    Lucarelli, Giuseppe; Rutigliano, Monica; Galleggiante, Vanessa; Giglio, Andrea; Palazzo, Silvano; Ferro, Matteo; Simone, Cristiano; Bettocchi, Carlo; Battaglia, Michele; Ditonno, Pasquale

    2015-01-01

    Metabolomic profiling offers a powerful methodology for understanding the perturbations of biochemical systems occurring during a disease process. During neoplastic transformation, prostate cells undergo metabolic reprogramming to satisfy the demands of growth and proliferation. An early event in prostate cell transformation is the loss of capacity to accumulate zinc. This change is associated with a higher energy efficiency and increased lipid biosynthesis for cellular proliferation, membrane formation and cell signaling. Moreover, recent studies have shown that sarcosine, an N-methyl derivative of glycine, was significantly increased during disease progression from normal to localized to metastatic prostate cancer. Mapping the metabolomic profiles to their respective biochemical pathways showed an upregulation of androgen-induced protein synthesis, an increased amino acid metabolism and a perturbation of nitrogen breakdown pathways, along with high total choline-containing compounds and phosphocholine levels. In this review, the role of emerging biomarkers is summarized, based on the current understanding of the prostate cancer metabolome.

  10. Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans

    DTIC Science & Technology

    2013-10-01

    latter transcription factor but rather dependent on serum deprivation- induced stress. Our findings point to a novel intracellular mechanism, which...e5611. 29. Ling H, Sylvestre JR, Jolicoeur P. Notch1- induced mammary tumor development is cyclin D1- dependent and correlates with expansion of pre...lung cancer. Based on the notions that: 1) smoking- induced injury alters mRNA and microRNA (miRNA) expression profiles in airway epithelium [5-7

  11. Preeclampsia-Associated Hormonal Profiles and Reduced Breast Cancer Risk Among Older Mothers

    DTIC Science & Technology

    2003-04-01

    Preeclampsia has been linked to reduced breast cancer risk, and this reduction may be especially marked among women who bear their first child later...in life. In this ongoing case-control study, we examine the hormonal profiles of older Colorado mothers with and without a history of preeclampsia in...premenopausal, and are free of serious chronic disease. Cases are 14 Denver area women who experienced preeclampsia in their first pregnancy; controls are 13

  12. Proteome profiling of human epithelial ovarian cancer cell line TOV-112D.

    PubMed

    Gagné, Jean-Philippe; Gagné, Pierre; Hunter, Joanna M; Bonicalzi, Marie-Eve; Lemay, Jean-François; Kelly, Isabelle; Le Page, Cécile; Provencher, Diane; Mes-Masson, Anne-Marie; Droit, Amaud; Bourgais, David; Poirier, Guy G

    2005-07-01

    A proteome profiling of the epithelial ovarian cancer cell line TOV-112D was initiated as a protein expression reference in the study of ovarian cancer. Two complementary proteomic approaches were used in order to maximise protein identification: two-dimensional gel electrophoresis (2DE) protein separation coupled to matrix assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and one-dimensional gel electrophoresis (1DE) coupled to liquid-chromatography tandem mass spectrometry (LC MS/MS). One hundred and seventy-two proteins have been identified among 288 spots selected on two-dimensional gels and a total of 579 proteins were identified with the 1DE LC MS/MS approach. This proteome profiling covers a wide range of protein expression and identifies several proteins known for their oncogenic properties. Bioinformatics tools were used to mine databases in order to determine whether the identified proteins have previously been implicated in pathways associated with carcinogenesis or cell proliferation. Indeed, several of the proteins have been reported to be specific ovarian cancer markers while others are common to many tumorigenic tissues or proliferating cells. The diversity of proteins found and their association with known oncogenic pathways validate this proteomic approach. The proteome 2D map of the TOV-112D cell line will provide a valuable resource in studies on differential protein expression of human ovarian carcinomas while the 1DE LC MS/MS approach gives a picture of the actual protein profile of the TOV-112D cell line. This work represents one of the most complete ovarian protein expression analysis reports to date and the first comparative study of gene expression profiling and proteomic patterns in ovarian cancer.

  13. Identification of a potential ovarian cancer stem cell gene expression profile from advanced stage papillary serous ovarian cancer.

    PubMed

    Vathipadiekal, Vinod; Saxena, Deepa; Mok, Samuel C; Hauschka, Peter V; Ozbun, Laurent; Birrer, Michael J

    2012-01-01

    Identification of gene expression profiles of cancer stem cells may have significant implications in the understanding of tumor biology and for the design of novel treatments targeted toward these cells. Here we report a potential ovarian cancer stem cell gene expression profile from isolated side population of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma. Affymetrix U133 Plus 2.0 microarrays were used to interrogate the differentially expressed genes between side population (SP) and main population (MP), and the results were analyzed by paired T-test using BRB-ArrayTools. We identified 138 up-regulated and 302 down-regulated genes that were differentially expressed between all 10 SP/MP pairs. Microarray data was validated using qRT-PCR and17/19 (89.5%) genes showed robust correlations between microarray and qRT-PCR expression data. The Pathway Studio analysis identified several genes involved in cell survival, differentiation, proliferation, and apoptosis which are unique to SP cells and a mechanism for the activation of Notch signaling is identified. To validate these findings, we have identified and isolated SP cells enriched for cancer stem cells from human ovarian cancer cell lines. The SP populations were having a higher colony forming efficiency in comparison to its MP counterpart and also capable of sustained expansion and differentiation in to SP and MP phenotypes. 50,000 SP cells produced tumor in nude mice whereas the same number of MP cells failed to give any tumor at 8 weeks after injection. The SP cells demonstrated a dose dependent sensitivity to specific γ-secretase inhibitors implicating the role of Notch signaling pathway in SP cell survival. Further the generated SP gene list was found to be enriched in recurrent ovarian cancer tumors.

  14. Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells

    PubMed Central

    Liang, Yuh-Jin; Ding, Yao; Levery, Steven B.; Lobaton, Marlin; Handa, Kazuko; Hakomori, Sen-itiroh

    2013-01-01

    Previous studies demonstrated that certain glycosphingolipids (GSLs) are involved in various cell functions, such as cell growth and motility. Recent studies showed changes in GSL expression during differentiation of human embryonic stem cells; however, little is known about expression profiles of GSLs in cancer stem cells (CSCs). CSCs are a small subpopulation in cancer and are proposed as cancer-initiating cells, have been shown to be resistant to numerous chemotherapies, and may cause cancer recurrence. Here, we analyzed GSLs expressed in human breast CSCs by applying a CSC model induced through epithelial–mesenchymal transition, using mass spectrometry, TLC immunostaining, and cell staining. We found that (i) Fuc-(n)Lc4Cer and Gb3Cer were drastically reduced in CSCs, whereas GD2, GD3, GM2, and GD1a were greatly increased in CSCs; (ii) among various glycosyltransferases tested, mRNA levels for ST3GAL5, B4GALNT1, ST8SIA1, and ST3GAL2 were increased in CSCs, which could explain the increased expression of GD3, GD2, GM2, and GD1a in CSCs; (iii) the majority of GD2+ cells and GD3+ cells were detected in the CD44hi/CD24lo cell population; and (iv) knockdown of ST8SIA1 and B4GALNT1 significantly reduced the expression of GD2 and GD3 and caused a phenotype change from CSC to a non-CSC, which was detected by reduced mammosphere formation and cell motility. Our results provide insight into GSL profiles in human breast CSCs, indicate a functional role of GD2 and GD3 in CSCs, and suggest a possible novel approach in targeting human breast CSCs to interfere with cancer recurrence. PMID:23479608

  15. Differential expression profiles of glycosphingolipids in human breast cancer stem cells vs. cancer non-stem cells.

    PubMed

    Liang, Yuh-Jin; Ding, Yao; Levery, Steven B; Lobaton, Marlin; Handa, Kazuko; Hakomori, Sen-itiroh

    2013-03-26

    Previous studies demonstrated that certain glycosphingolipids (GSLs) are involved in various cell functions, such as cell growth and motility. Recent studies showed changes in GSL expression during differentiation of human embryonic stem cells; however, little is known about expression profiles of GSLs in cancer stem cells (CSCs). CSCs are a small subpopulation in cancer and are proposed as cancer-initiating cells, have been shown to be resistant to numerous chemotherapies, and may cause cancer recurrence. Here, we analyzed GSLs expressed in human breast CSCs by applying a CSC model induced through epithelial-mesenchymal transition, using mass spectrometry, TLC immunostaining, and cell staining. We found that (i) Fuc-(n)Lc4Cer and Gb3Cer were drastically reduced in CSCs, whereas GD2, GD3, GM2, and GD1a were greatly increased in CSCs; (ii) among various glycosyltransferases tested, mRNA levels for ST3GAL5, B4GALNT1, ST8SIA1, and ST3GAL2 were increased in CSCs, which could explain the increased expression of GD3, GD2, GM2, and GD1a in CSCs; (iii) the majority of GD2+ cells and GD3+ cells were detected in the CD44(hi)/CD24(lo) cell population; and (iv) knockdown of ST8SIA1 and B4GALNT1 significantly reduced the expression of GD2 and GD3 and caused a phenotype change from CSC to a non-CSC, which was detected by reduced mammosphere formation and cell motility. Our results provide insight into GSL profiles in human breast CSCs, indicate a functional role of GD2 and GD3 in CSCs, and suggest a possible novel approach in targeting human breast CSCs to interfere with cancer recurrence.

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

    PubMed

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

    2017-10-01

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

  17. Benzodiazepines use and breast cancer risk: A population-based study and gene expression profiling evidence.

    PubMed

    Iqbal, Usman; Chang, Tzu-Hao; Nguyen, Phung-Anh; Syed-Abdul, Shabbir; Yang, Hsuan-Chia; Huang, Chih-Wei; Atique, Suleman; Yang, Wei-Chung; Moldovan, Max; Jian, Wen-Shan; Hsu, Min-Huei; Yen, Yun; Jack Li, Yu-Chuan

    2017-08-26

    The aim of this study was to investigate whether long-term use of Benzodiazepines (BZDs) is associated with breast cancer risk through the combination of population-based observational and gene expression profiling evidence. We conducted a population-based case-control study by using 1998 to 2009 year Taiwan National Health Insurance Research Database and investigated the association between BZDs use and breast cancer risk. We selected subjects age of > 20 years old and six eligible controls matched for age, sex and the index date (i.e., free of any cancer at the case diagnosis date) by using propensity scores. A bioinformatics analysis approach was also performed for the identification of oncogenesis effects of BZDs on breast cancer. We used breast cancer gene expression data from the Cancer Genome Atlas and perturbagen signatures of BZDs from the Library of Integrated Cellular Signatures database in order to identify the oncogenesis effects of BZDs on breast cancer. We found evidence of increased breast cancer risk for diazepam (OR, 1.16; 95%CI, 0.95-1.42; connectivity score [CS], 0.3016), zolpidem (OR, 1.11; 95%CI, 0.95-1.30; CS, 0.2738), but not for lorazepam (OR, 1.04; 95%CI, 0.89-1.23; CS, -0.2952) consistently in both methods. The finding for alparazolam was contradictory from the two methods. Diazepam and zolpidem trends showed association, although not statistically significant, with breast cancer risk in both epidemiological and bioinformatics analyses outcomes. The methodological value of our study is in introducing the way of combining epidemiological and bioinformatics approaches in order to answer a common scientific question. Combining the two approaches would be a substantial step towards uncovering, validation and further application of previously unknown scientific knowledge to the emerging field of precision medicine informatics. Copyright © 2017. Published by Elsevier Inc.

  18. Breast cancer risk and germline genomic profiling of women with neurofibromatosis type 1 who developed breast cancer.

    PubMed

    Wang, Xia; Teer, Jamie K; Tousignant, Renee N; Levin, Albert M; Boulware, David; Chitale, Dhananjay A; Shaw, Brandon M; Chen, Zhihua; Zhang, Yonghong; Blakeley, Jaishri O; Acosta, Maria T; Messiaen, Ludwine M; Korf, Bruce R; Tainsky, Michael A

    2017-09-10

    NF1 mutations predispose to neurofibromatosis type 1 (NF1) and women with NF1 have a moderately elevated risk for breast cancer, especially under age 50. Germline genomic analysis may better define the risk so screening and prevention can be applied to the individuals who benefit the most. Survey conducted in several neurofibromatosis clinics in the United States has demonstrated a 17.2% lifetime risk of breast cancer in women affected with NF1. Cumulated risk to age 50 is estimated to be 9.27%. For genomic profiling, fourteen women with NF1 and a history of breast cancer were recruited and underwent whole exome sequencing (WES), targeted genomic DNA based and RNA-based analysis of the NF1 gene. Deleterious NF1 pathogenic variants were identified in each woman. Frameshift mutations because of deletion/duplication/complex rearrangement were found in 50% (7/14) of the cases, nonsense mutations in 21% (3/14), in-frame splice mutations in 21% (3/14), and one case of missense mutation (7%, 1/14). No deleterious mutation was found in the following high/moderate-penetrance breast cancer genes: ATM, BRCA1, BRCA2, BARD1, BRIP1, CDH1, CHEK2, FANCC, MRE11A, NBN, PALB2, PTEN, RAD50, RAD51C, TP53, and STK11. Twenty-five rare or common variants in cancer related genes were discovered and may have contributed to the breast cancers in these individuals. Breast cancer predisposition modifiers in women with NF1 may involve a great variety of molecular and cellular functions. © 2017 Wiley Periodicals, Inc.

  19. Limitations in SELDI-TOF MS whole serum proteomic profiling with IMAC surface to specifically detect colorectal cancer

    PubMed Central

    2009-01-01

    Background Surface enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS) analysis on serum samples was reported to be able to detect colorectal cancer (CRC) from normal or control patients. We carried out a validation study of a SELDI-TOF MS approach with IMAC surface sample processing to identify CRC. Methods A retrospective cohort of 338 serum samples including 154 CRCs, 67 control cancers and 117 non-cancerous conditions was profiled using SELDI-TOF-MS. Results No CRC "specific" classifier was found. However, a classifier consisting of two protein peaks separates cancer from non-cancerous conditions with high accuracy. Conclusion In this study, the SELDI-TOF-MS-based protein expression profiling approach did not perform to identify CRC. However, this technique is promising in distinguishing patients with cancer from a non-cancerous population; it may be useful for monitoring recurrence of CRC after treatment. PMID:19689818

  20. A Comparison of the Biological Features of Prostate Cancer with (PSA+, PSMA+) Profile according to RKIP

    PubMed Central

    Ben Jemaa, Awatef; Bouraoui, Yosra; Sallami, Sataa; Nouira, Yassine; Oueslati, Ridha

    2013-01-01

    Purpose. To investigate differences in the biological features of the most immunoexpressed prostate cancer (PC) profiles (PSA+, PSMA+) according to the RKIP. Methods. 19 PC with dominant Gleason grade ≥8 were studied. Expression of PSA, PSMA, RKIP, Raf-1, MEK-1, ERK-1, ERK-2, p-Akt (T308), p-Akt (S473), NF-κB p50, and NF-κBp65 were detected immunohistochemically. Results. Loss of RKIP in the most immunoexpressed PC (PSA+, PSMA+) profile was associated with increased levels of PSA and PSMA expression. Intensities of immunoreactions to PSA and PSMA were higher in cancer cells negative for RKIP (12.51 ± 1.6 and 34.95 ± 1.92) compared to those positive for RKIP (4.68 ± 1.11 and 28.56 ± 0.91). In parallel, missing RKIP expression in PC patients with PSA+, PSMA+ profile was connected with increased components of both Raf-1/MEK/ERK and NF-κB (p65/p50), whereas Akt is activated independently of RKIP. Conclusions. Although characterized by the same (PSA+, PSMA+) profile, PC phenotype missing the RKIP related to invasive potential and greater biological aggressiveness reflected in overexpression of components of Raf-1/MEK/ERK and NF-κB (p65/p50) in which Akt is activated independently of RKIP. Taking into account the PC phenotypes according to RKIP among PSA-PSMA profiles may improve distinguishing them from cancers that will become more aggressive and therefore adapt the therapeutic strategies in those patients. PMID:23991415

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

    PubMed

    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.

  2. Genetic profiling of putative breast cancer stem cells from malignant pleural effusions

    PubMed Central

    Tiran, Verena; Stanzer, Stefanie; Heitzer, Ellen; Meilinger, Michael; Rossmann, Christopher; Lax, Sigurd; Tsybrovskyy, Oleksiy; Dandachi, Nadia; Balic, Marija

    2017-01-01

    A common symptom during late stage breast cancer disease is pleural effusion, which is related to poor prognosis. Malignant cells can be detected in pleural effusions indicating metastatic spread from the primary tumor site. Pleural effusions have been shown to be a useful source for studying metastasis and for isolating cells with putative cancer stem cell (CSC) properties. For the present study, pleural effusion aspirates from 17 metastatic breast cancer patients were processed to propagate CSCs in vitro. Patient-derived aspirates were cultured under sphere forming conditions and isolated primary cultures were further sorted for cancer stem cell subpopulations ALDH1+ and CD44+CD24-/low. Additionally, sphere forming efficiency of CSC and non-CSC subpopulations was determined. In order to genetically characterize the different tumor subpopulations, DNA was isolated from pleural effusions before and after cell sorting, and compared with corresponding DNA copy number profiles from primary tumors or bone metastasis using low-coverage whole genome sequencing (SCNA-seq). In general, unsorted cells had a higher potential to form spheres when compared to CSC subpopulations. In most cases, cell sorting did not yield sufficient cells for copy number analysis. A total of five from nine analyzed unsorted pleura samples (55%) showed aberrant copy number profiles similar to the respective primary tumor. However, most sorted subpopulations showed a balanced profile indicating an insufficient amount of tumor cells and low sensitivity of the sequencing method. Finally, we were able to establish a long term cell culture from one pleural effusion sample, which was characterized in detail. In conclusion, we confirm that pleural effusions are a suitable source for enrichment of putative CSC. However, sequencing based molecular characterization is impeded due to insufficient sensitivity along with a high number of normal contaminating cells, which are masking genetic alterations of

  3. Genetic profiling of putative breast cancer stem cells from malignant pleural effusions.

    PubMed

    Tiran, Verena; Stanzer, Stefanie; Heitzer, Ellen; Meilinger, Michael; Rossmann, Christopher; Lax, Sigurd; Tsybrovskyy, Oleksiy; Dandachi, Nadia; Balic, Marija

    2017-01-01

    A common symptom during late stage breast cancer disease is pleural effusion, which is related to poor prognosis. Malignant cells can be detected in pleural effusions indicating metastatic spread from the primary tumor site. Pleural effusions have been shown to be a useful source for studying metastasis and for isolating cells with putative cancer stem cell (CSC) properties. For the present study, pleural effusion aspirates from 17 metastatic breast cancer patients were processed to propagate CSCs in vitro. Patient-derived aspirates were cultured under sphere forming conditions and isolated primary cultures were further sorted for cancer stem cell subpopulations ALDH1+ and CD44+CD24-/low. Additionally, sphere forming efficiency of CSC and non-CSC subpopulations was determined. In order to genetically characterize the different tumor subpopulations, DNA was isolated from pleural effusions before and after cell sorting, and compared with corresponding DNA copy number profiles from primary tumors or bone metastasis using low-coverage whole genome sequencing (SCNA-seq). In general, unsorted cells had a higher potential to form spheres when compared to CSC subpopulations. In most cases, cell sorting did not yield sufficient cells for copy number analysis. A total of five from nine analyzed unsorted pleura samples (55%) showed aberrant copy number profiles similar to the respective primary tumor. However, most sorted subpopulations showed a balanced profile indicating an insufficient amount of tumor cells and low sensitivity of the sequencing method. Finally, we were able to establish a long term cell culture from one pleural effusion sample, which was characterized in detail. In conclusion, we confirm that pleural effusions are a suitable source for enrichment of putative CSC. However, sequencing based molecular characterization is impeded due to insufficient sensitivity along with a high number of normal contaminating cells, which are masking genetic alterations of

  4. Multicomponent, Tumor-Homing Chitosan Nanoparticles for Cancer Imaging and Therapy

    PubMed Central

    Key, Jaehong; Park, Kyeongsoon

    2017-01-01

    Current clinical methods for cancer diagnosis and therapy have limitations, although survival periods are increasing as medical technologies develop. In most cancer cases, patient survival is closely related to cancer stage. Late-stage cancer after metastasis is very challenging to cure because current surgical removal of cancer is not precise enough and significantly affects bystander normal tissues. Moreover, the subsequent chemotherapy and radiation therapy affect not only malignant tumors, but also healthy tissues. Nanotechnologies for cancer treatment have the clear objective of solving these issues. Nanoparticles have been developed to more accurately differentiate early-stage malignant tumors and to treat only the tumors while dramatically minimizing side effects. In this review, we focus on recent chitosan-based nanoparticles developed with the goal of accurate cancer imaging and effective treatment. Regarding imaging applications, we review optical and magnetic resonance cancer imaging in particular. Regarding cancer treatments, we review various therapeutic methods that use chitosan-based nanoparticles, including chemo-, gene, photothermal, photodynamic and magnetic therapies. PMID:28282891

  5. Multicomponent, Tumor-Homing Chitosan Nanoparticles for Cancer Imaging and Therapy.

    PubMed

    Key, Jaehong; Park, Kyeongsoon

    2017-03-08

    Current clinical methods for cancer diagnosis and therapy have limitations, although survival periods are increasing as medical technologies develop. In most cancer cases, patient survival is closely related to cancer stage. Late-stage cancer after metastasis is very challenging to cure because current surgical removal of cancer is not precise enough and significantly affects bystander normal tissues. Moreover, the subsequent chemotherapy and radiation therapy affect not only malignant tumors, but also healthy tissues. Nanotechnologies for cancer treatment have the clear objective of solving these issues. Nanoparticles have been developed to more accurately differentiate early-stage malignant tumors and to treat only the tumors while dramatically minimizing side effects. In this review, we focus on recent chitosan-based nanoparticles developed with the goal of accurate cancer imaging and effective treatment. Regarding imaging applications, we review optical and magnetic resonance cancer imaging in particular. Regarding cancer treatments, we review various therapeutic methods that use chitosan-based nanoparticles, including chemo-, gene, photothermal, photodynamic and magnetic therapies.

  6. Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach.

    PubMed

    Domenyuk, Valeriy; Zhong, Zhenyu; Stark, Adam; Xiao, Nianqing; O'Neill, Heather A; Wei, Xixi; Wang, Jie; Tinder, Teresa T; Tonapi, Sonal; Duncan, Janet; Hornung, Tassilo; Hunter, Andrew; Miglarese, Mark R; Schorr, Joachim; Halbert, David D; Quackenbush, John; Poste, George; Berry, Donald A; Mayer, Günter; Famulok, Michael; Spetzler, David

    2017-02-20

    Technologies capable of characterizing the full breadth of cellular systems need to be able to measure millions of proteins, isoforms, and complexes simultaneously. We describe an approach that fulfils this criterion: Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT). ADAPT employs an enriched library of single-stranded oligodeoxynucleotides (ssODNs) to profile complex biological samples, thus achieving an unprecedented coverage of system-wide, native biomolecules. We used ADAPT as a highly specific profiling tool that distinguishes women with or without breast cancer based on circulating exosomes in their blood. To develop ADAPT, we enriched a library of ~10(11) ssODNs for those associating with exosomes from breast cancer patients or controls. The resulting 10(6) enriched ssODNs were then profiled against plasma from independent groups of healthy and breast cancer-positive women. ssODN-mediated affinity purification and mass spectrometry identified low-abundance exosome-associated proteins and protein complexes, some with known significance in both normal homeostasis and disease. Sequencing of the recovered ssODNs provided quantitative measures that were used to build highly accurate multi-analyte signatures for patient classification. Probing plasma from 500 subjects with a smaller subset of 2000 resynthesized ssODNs stratified healthy, breast biopsy-negative, and -positive women. An AUC of 0.73 was obtained when comparing healthy donors with biopsy-positive patients.

  7. Plasma Exosome Profiling of Cancer Patients by a Next Generation Systems Biology Approach

    PubMed Central

    Domenyuk, Valeriy; Zhong, Zhenyu; Stark, Adam; Xiao, Nianqing; O’Neill, Heather A.; Wei, Xixi; Wang, Jie; Tinder, Teresa T.; Tonapi, Sonal; Duncan, Janet; Hornung, Tassilo; Hunter, Andrew; Miglarese, Mark R.; Schorr, Joachim; Halbert, David D.; Quackenbush, John; Poste, George; Berry, Donald A.; Mayer, Günter; Famulok, Michael; Spetzler, David

    2017-01-01

    Technologies capable of characterizing the full breadth of cellular systems need to be able to measure millions of proteins, isoforms, and complexes simultaneously. We describe an approach that fulfils this criterion: Adaptive Dynamic Artificial Poly-ligand Targeting (ADAPT). ADAPT employs an enriched library of single-stranded oligodeoxynucleotides (ssODNs) to profile complex biological samples, thus achieving an unprecedented coverage of system-wide, native biomolecules. We used ADAPT as a highly specific profiling tool that distinguishes women with or without breast cancer based on circulating exosomes in their blood. To develop ADAPT, we enriched a library of ~1011 ssODNs for those associating with exosomes from breast cancer patients or controls. The resulting 106 enriched ssODNs were then profiled against plasma from independent groups of healthy and breast cancer-positive women. ssODN-mediated affinity purification and mass spectrometry identified low-abundance exosome-associated proteins and protein complexes, some with known significance in both normal homeostasis and disease. Sequencing of the recovered ssODNs provided quantitative measures that were used to build highly accurate multi-analyte signatures for patient classification. Probing plasma from 500 subjects with a smaller subset of 2000 resynthesized ssODNs stratified healthy, breast biopsy-negative, and -positive women. An AUC of 0.73 was obtained when comparing healthy donors with biopsy-positive patients. PMID:28218293

  8. Characterizing Tyrosine Phosphorylation Signaling in Lung Cancer Using SH2 Profiling

    PubMed Central

    Li, Jiannong; Bai, Yun; Koomen, John; Mayer, Bruce J.; Haura, Eric B.

    2010-01-01

    Background Tyrosine kinases drive the proliferation and survival of many human cancers. Thus profiling the global state of tyrosine phosphorylation of a tumor is likely to provide a wealth of information that can be used to classify tumors for prognosis and prediction. However, the comprehensive analysis of tyrosine phosphorylation of large numbers of human cancer specimens is technically challenging using current methods. Methodology/Principal Findings We used a phosphoproteomic method termed SH2 profiling to characterize the global state of phosphotyrosine (pTyr) signaling in human lung cancer cell lines. This method quantifies the phosphorylated binding sites for SH2 domains, which are used by cells to respond to changes in pTyr during signaling. Cells could be grouped based on SH2 binding patterns, with some clusters correlated with EGF receptor (EGFR) or K-RAS mutation status. Binding of specific SH2 domains, most prominently RAS pathway activators Grb2 and ShcA, correlated with EGFR mutation and sensitivity to the EGFR inhibitor erlotinib. SH2 binding patterns also reflected MET activation and could identify cells driven by multiple kinases. The pTyr responses of cells treated with kinase inhibitors provided evidence of distinct mechanisms of inhibition. Conclusions/Significance This study illustrates the potential of modular protein domains and their proteomic binding profiles as powerful molecular diagnostic tools for tumor classification and biomarker identification. PMID:20976048

  9. Presurgical symptom profiles predict quality of life 2 years after surgery in women with breast cancer.

    PubMed

    Chen, Mei-Ling; Liu, Li-Ni; Miaskowski, Christine; Chen, Shin-Cheh; Lin, Yung-Chang; Wang, Jong-Shyan

    2016-01-01

    Higher symptom burden in oncology patients is associated with poorer quality of life (QOL). However, the long-term predictive relationship between pre-treatment symptom profiles and QOL is unknown. The aim of this study was to identify subgroups of breast cancer patients based on their presurgical symptom profiles and to examine the predictive effect of group membership on QOL 2 years after surgery. Data were analyzed from a longitudinal study of women's (N = 198) symptoms after breast cancer surgery. Patient subgroups were identified by latent class analysis based on presurgical severity of five symptoms (i.e., attentional and physical fatigue, sleep disturbance, depression, and anxiety). Among these 198 women, quality of life 2 years after surgery was available for 97. Group differences in QOL were examined by general linear models. We identified four distinct patient groups. Group A (All Low) had low levels of all symptoms. Group B (Low Fatigue and Moderate Mood) was characterized by low attentional and physical fatigue but moderate sleep disturbance, depression, and anxiety. Group C (All Moderate) was characterized by moderate levels of all five symptoms. Group D was characterized by moderate attentional and physical fatigue and severe sleep disturbance, depression, and anxiety (Moderate Fatigue and High Mood). Group D had significantly lower overall QOL scores 2 years after surgery than Group A (p = 0.002). Breast cancer patients' presurgical symptom profile had a long-term predictive effect on QOL. Routine assessment of patients' pre-treatment symptom is suggested to identify high risk group.

  10. No impact of passive smoke on the somatic profile of lung cancers in never-smokers.

    PubMed

    Couraud, Sébastien; Debieuvre, Didier; Moreau, Lionel; Dumont, Patrick; Margery, Jacques; Quoix, Elisabeth; Duvert, Bernard; Cellerin, Laurent; Baize, Nathalie; Taviot, Bruno; Coudurier, Marie; Cadranel, Jacques; Missy, Pascale; Morin, Franck; Mornex, Jean-François; Zalcman, Gérard; Souquet, Pierre-Jean

    2015-05-01

    EGFR and HER2 mutations and ALK rearrangement are known to be related to lung cancer in never-smokers, while KRAS, BRAF and PIK3CA mutations are typically observed among smokers. There is still debate surrounding whether never-smokers exposed to passive smoke exhibit a "smoker-like" somatic profile compared with unexposed never-smokers. Passive smoke exposure was assessed in the French BioCAST/IFCT-1002 never-smoker lung cancer cohort and routine molecular profiles analyses were compiled. Of the 384 patients recruited into BioCAST, 319 were tested for at least one biomarker and provided data relating to passive smoking. Overall, 219 (66%) reported having been exposed to passive smoking. No significant difference was observed between mutation frequency and passive smoke exposure (EGFR mutation: 46% in never exposed versus 41% in ever exposed; KRAS: 7% versus 7%; ALK: 13% versus 11%; HER2: 4% versus 5%; BRAF: 6% versus 5%; PIK3CA: 4% versus 2%). We observed a nonsignificant trend for a negative association between EGFR mutation and cumulative duration of passive smoke exposure. No association was found for other biomarkers. There is no clear association between passive smoke exposure and somatic profile in lifelong, never-smoker lung cancer.

  11. Profiles of Health Competence Beliefs Among Young Adult Survivors of Childhood Cancer

    PubMed Central

    Brier, Moriah J.; DeRosa, Branlyn Werba; Hocking, Matthew C.; Schwartz, Lisa A.; Ginsberg, Jill P.; Hobbie, Wendy; Ittenbach, Richard F.

    2011-01-01

    Purpose: The goal of this study was to identify profiles of young adult (YA)-aged cancer survivors' beliefs about their health and well-being. Survivors' beliefs and their associated psychosocial and demographic characteristics may be clinically useful in survivorship care. Patients and methods: YA survivors of pediatric leukemias (n=51), lymphomas (n=24), and solid tumors (n=44), aged 18–29 years old (N=119), were categorized using cluster analysis based on their responses to the Health Competence Beliefs Inventory, a measure assessing beliefs about their health, satisfaction with healthcare, autonomy, and cognitive competence. Profiles of beliefs generated by cluster analysis were examined using self-report measures of health problems, distress, demographics, and provider-reported health problems and cancer treatment intensity. Results: Three distinct clusters were identified: Adaptive (n=54), Low Autonomy (n=25), and Vulnerable (n=40). Adaptive survivors had positive beliefs, low distress, and minimal health problems. The Low Autonomy survivors were similar to those in the Adaptive cluster except they had low autonomy beliefs and the majority reported living with their parents. The Vulnerable cluster had more negative beliefs, the most medical problems, and the highest levels of distress. Conclusion: Health competence belief profiles identified unique subsets of YA survivors of pediatric cancer that have potentially distinct risk factors. Categorizing survivors by health belief patterns may help healthcare providers treat and educate their patients in ways that are tailored to individual survivors' needs and risks. PMID:23610738

  12. Cancer cell line identification by short tandem repeat profiling: power and limitations.

    PubMed

    Parson, Walther; Kirchebner, Romana; Mühlmann, Roswitha; Renner, Kathrin; Kofler, Anita; Schmidt, Stefan; Kofler, Reinhard

    2005-03-01

    Cancer cell lines are used worldwide in biological research, and data interpretation depends on unambiguous attribution of the respective cell line to its original source. Short-tandem-repeat (STR) profiling (DNA fingerprinting) is the method of choice for this purpose; however, the genetic stability of cell lines under various experimental conditions is not well defined. We tested the effect of long-term culture, subcloning, and generation of drug-resistant subclones on fingerprinting profiles in four widely used leukemia cell lines. The DNA fingerprinting profile remained unaltered in two of them (U937 and K562) throughout 12 months in culture, and the vast majority of subclones derived therefrom by limiting dilution after long-term culture revealed the same profile, indicating a high degree of stability and clonotypic homogeneity. In contrast, two other cell lines (CCRF-CEM and Jurkat) showed marked alterations in DNA fingerprinting profiles during long-term culture. Limiting dilution subcloning revealed extensive clonotypic heterogeneity with subclones differing in up to eight STR loci from the parental culture. Similar heterogeneity was observed in subclones generated by selection culture for drug resistance where DNA fingerprinting proved useful in identifying possible resistance mechanisms. Thus, common tissue culture procedures may dramatically affect the fingerprinting profile of certain cell lines and thus render definition of their origin difficult.

  13. Genomic and phenotypic profiles of two Brazilian breast cancer cell lines derived from primary human tumors

    PubMed Central

    CORRÊA, NATÁSSIA C.R.; KUASNE, HELLEN; FARIA, JERUSA A.Q.A.; SEIXAS, CIÇA C.S.; SANTOS, IRIA G.D.; ABREU, FRANCINE B.; NONOGAKI, SUELY; ROCHA, RAFAEL M.; SILVA, GERLUZA APARECIDA BORGES; GOBBI, HELENICE; ROGATTO, SILVIA R.; GOES, ALFREDO M.; GOMES, DAWIDSON A.

    2013-01-01

    Breast cancer is the most common type of cancer among women worldwide. Research using breast cancer cell lines derived from primary tumors may provide valuable additional knowledge regarding this type of cancer. Therefore, the aim of this study was to investigate the phenotypic profiles of MACL-1 and MGSO-3, the only Brazilian breast cancer cell lines available for comparative studies. We evaluated the presence of hormone receptors, proliferation, differentiation and stem cell markers, using immunohistochemical staining of the primary tumor, cultured cells and xenografts implanted in immunodeficient mice. We also investigated the ability of the cell lines to form colonies and copy number alterations by array comparative genomic hybridization. Histopathological analysis showed that the invasive primary tumor from which the MACL-1 cell line was derived, was a luminal A subtype carcinoma, while the ductal carcinoma in situ (DCIS) that gave rise to the MGSO-3 cell line was a HER2 subtype tumor, both showing different proliferation levels. The cell lines and the tumor xenografts in mice preserved their high proliferative potential, but did not maintain the expression of the other markers assessed. This shift in expression may be due to the selection of an ‘establishment’ phenotype in vitro. Whole-genome DNA evaluation showed a large amount of copy number alterations (CNAs) in the two cell lines. These findings render MACL-1 and MGSO-3 the first characterized Brazilian breast cancer cell lines to be potentially used for comparative research. PMID:23404580

  14. Molecular profiling of thyroid cancer subtypes using large-scale text mining

    PubMed Central

    2014-01-01

    Background Thyroid cancer is the most common endocrine tumor with a steady increase in incidence. It is classified into multiple histopathological subtypes with potentially distinct molecular mechanisms. Identifying the most relevant genes and biological pathways reported in the thyroid cancer literature is vital for understanding of the disease and developing targeted therapeutics. Results We developed a large-scale text mining system to generate a molecular profiling of thyroid cancer subtypes. The system first uses a subtype classification method for the thyroid cancer literature, which employs a scoring scheme to assign different subtypes to articles. We evaluated the classification method on a gold standard derived from the PubMed Supplementary Concept annotations, achieving a micro-average F1-score of 85.9% for primary subtypes. We then used the subtype classification results to extract genes and pathways associated with different thyroid cancer subtypes and successfully unveiled important genes and pathways, including some instances that are missing from current manually annotated databases or most recent review articles. Conclusions Identification of key genes and pathways plays a central role in understanding the molecular biology of thyroid cancer. An integration of subtype context can allow prioritized screening for diagnostic biomarkers and novel molecular targeted therapeutics. Source code used for this study is made freely available online at https://github.com/chengkun-wu/GenesThyCan. PMID:25521965

  15. Proteomic profiling of small-molecule inhibitors reveals dispensability of MTH1 for cancer cell survival

    PubMed Central

    Kawamura, Tatsuro; Kawatani, Makoto; Muroi, Makoto; Kondoh, Yasumitsu; Futamura, Yushi; Aono, Harumi; Tanaka, Miho; Honda, Kaori; Osada, Hiroyuki

    2016-01-01

    Since recent publications suggested that the survival of cancer cells depends on MTH1 to avoid incorporation of oxidized nucleotides into the cellular DNA, MTH1 has attracted attention as a potential cancer therapeutic target. In this study, we identified new purine-based MTH1 inhibitors by chemical array screening. However, although the MTH1 inhibitors identified in this study targeted cellular MTH1, they exhibited only weak cytotoxicity against cancer cells compared to recently reported first-in-class inhibitors. We performed proteomic profiling to investigate the modes of action by which chemically distinct MTH1 inhibitors induce cancer cell death, and found mechanistic differences among the first-in-class MTH1 inhibitors. In particular, we identified tubulin as the primary target of TH287 and TH588 responsible for the antitumor effects despite the nanomolar MTH1-inhibitory activity in vitro. Furthermore, overexpression of MTH1 did not rescue cells from MTH1 inhibitor–induced cell death, and siRNA-mediated knockdown of MTH1 did not suppress cancer cell growth. Taken together, we conclude that the cytotoxicity of MTH1 inhibitors is attributable to off-target effects and that MTH1 is not essential for cancer cell survival. PMID:27210421

  16. MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing

    PubMed Central

    Zhang, Yuanwei; Xu, Bo; Zhou, Jun; Fan, Song; Hao, Zongyao; Shi, Haoqiang; Zhang, Xiansheng; Kong, Rui; Xu, Lingfan; Gao, Jingjing; Zou, Duohong; Liang, Chaozhao

    2015-01-01

    Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-β signaling pathways, which were all well-established to participate in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights

  17. MicroRNA Expression Profile in Penile Cancer Revealed by Next-Generation Small RNA Sequencing.

    PubMed

    Zhang, Li; Wei, Pengfei; Shen, Xudong; Zhang, Yuanwei; Xu, Bo; Zhou, Jun; Fan, Song; Hao, Zongyao; Shi, Haoqiang; Zhang, Xiansheng; Kong, Rui; Xu, Lingfan; Gao, Jingjing; Zou, Duohong; Liang, Chaozhao

    2015-01-01

    Penile cancer (PeCa) is a relatively rare tumor entity but possesses higher morbidity and mortality rates especially in developing countries. To date, the concrete pathogenic signaling pathways and core machineries involved in tumorigenesis and progression of PeCa remain to be elucidated. Several studies suggested miRNAs, which modulate gene expression at posttranscriptional level, were frequently mis-regulated and aberrantly expressed in human cancers. However, the miRNA profile in human PeCa has not been reported before. In this present study, the miRNA profile was obtained from 10 fresh penile cancerous tissues and matched adjacent non-cancerous tissues via next-generation sequencing. As a result, a total of 751 and 806 annotated miRNAs were identified in normal and cancerous penile tissues, respectively. Among which, 56 miRNAs with significantly different expression levels between paired tissues were identified. Subsequently, several annotated miRNAs were selected randomly and validated using quantitative real-time PCR. Compared with the previous publications regarding to the altered miRNAs expression in various cancers and especially genitourinary (prostate, bladder, kidney, testis) cancers, the most majority of deregulated miRNAs showed the similar expression pattern in penile cancer. Moreover, the bioinformatics analyses suggested that the putative target genes of differentially expressed miRNAs between cancerous and matched normal penile tissues were tightly associated with cell junction, proliferation, growth as well as genomic instability and so on, by modulating Wnt, MAPK, p53, PI3K-Akt, Notch and TGF-β signaling pathways, which were all well-established to participate in cancer initiation and progression. Our work presents a global view of the differentially expressed miRNAs and potentially regulatory networks of their target genes for clarifying the pathogenic transformation of normal penis to PeCa, which research resource also provides new insights

  18. Liquid Profiling of Circulating Nucleic Acids as a Novel Tool for the Management of Cancer Patients.

    PubMed

    Holdenrieder, Stefan

    2016-01-01

    Liquid profiling is a traditional concept in laboratory diagnostics using patterns of blood-derived biochemical molecules for disease detection and characterization. Beyond protein and cellular parameters, molecular biomarkers at the DNA, RNA and miRNA level have been developed as promising diagnostic tools in metabolic and malignant diseases as new technologies for ultrasensitive profiling of nucleic acids in blood and body fluids became available. In cancer disease, they are successfully applied for the stratification of patients for individually tailored therapies, treatment monitoring and the sensitive detection of minimal residual disease. Due to its minimally invasive nature, blood-based qualitative and quantitative determinations of targeted and global molecular changes can be applied serially and complement well-established molecular tissue diagnostics. Interdisciplinary interaction between laboratory medicine, pathology and human genetics will speed up the development of liquid nucleic acid profiling as a most valuable tool for precision medicine.

  19. [Enrichment analysis of Fanconi anemia gene expression profiles in cancer related genesets].

    PubMed

    Zhou, Quan-quan; Wang, Xiao-juan; Zhu, Xiao-fan; Yuan, Wei-ping; Cheng, Tao

    2012-05-01

    To investigate the underlying tumor susceptibility mechanisms and reasons for the high risk of cancer in Fanconi anemia (FA). Gene Set Enrichment Analysis (GSEA) was performed to compare gene expression profiles between 21 FA patients' bone marrow (BM) mononuclear cell (BMNC) and 11 normal controls in cancer related gene sets from NCBI GEO database, then core enriched genes were identified by further investigation. Through enrichment analyzing biological processes of gene ontology sets and structural genomic gene sets between FA expression profiles and control, more details related with its tumor susceptibility had been revealed. Compared with normal control, gene expression in FA group had significant been enriched in resistance to Bcl-2 inhibitor gene set, fibroblast growth factors signalling pathways, insulin and insulin-like growth factors (IGF) signalling pathways induced cancer genesis gene sets. The high level of D4S234E, SST, FGFs, IGFs, FGFRs and IGFBP expression provided an initiate environment for tumorgenesis and drug resistance. There were significant differences in biogenesis extracellular molecules and cytomembrane structure organizations between FA and control. Genes with promoter regions around transcription start sites containing either motif RRCAGGTGNCV or CCTNTMAGA were enriched and those former genes match annotation for tumorgenic transcription factor 3 (TCF3). The high tumor susceptibility of FA patients may be closely related with the dramatic changes in cancer related growth factors and hormones environment. This study provides new insights into tumor susceptibility mechanism in FA patients.

  20. Common and contrasting genomic profiles among the major human lung cancer subtypes.

    PubMed

    Tonon, G; Brennan, C; Protopopov, A; Maulik, G; Feng, B; Zhang, Y; Khatry, D B; You, M J; Aguirre, A J; Martin, E S; Yang, Z; Ji, H; Chin, L; Wong, K-K; Depinho, R A

    2005-01-01

    Lung cancer is the leading cause of cancer mortality worldwide. With the recent success of molecularly targeted therapies in this disease, a detailed knowledge of the spectrum of genetic lesions in lung cancer represents a critical step in the development of additional effective agents. An integrated high-resolution survey of regional amplifications and deletions and gene expression profiling of non-small-cell lung cancers (NSCLC) identified 93 focal high-confidence copy number alterations (CNAs), with 21 spanning less than 0.5 Mb with a median of five genes. Most CNAs were novel and included high-amplitude amplification and homozygous deletion events. Pathogenic relevance of these genomic alterations was further reinforced by their recurrence and overlap with focal alterations of other tumor types. Additionally, the comparison of the genomic profiles of the two major subtypes of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SCC), showed an almost complete overlap with the exception of one amplified region on chromosome 3, specific for SCC. Among the few genes overexpressed within this amplicon was p63, a known regulator of squamous cell differentiation. These findings suggest that the AC and SCC subtypes may arise from a common cell of origin and they are driven to their distinct phenotypic end points by altered expression of a limited number of key genes such as p63.

  1. Symptoms, unbearability and the nature of suffering in terminal cancer patients dying at home: a prospective primary care study

    PubMed Central

    2013-01-01

    Background Primary care physicians provide palliative home care. In cancer patients dying at home in the Netherlands (45% of all cancer patients) euthanasia in about one out of every seven patients indicates unbearable suffering. Symptom prevalence, relationship between intensity of symptoms and unbearable suffering, evolvement of symptoms and unbearability over time and quality of unbearable suffering were studied in end-of-life cancer patients in primary care. Methods 44 general practitioners during three years recruited cancer patients estimated to die within six months. Every two months patients quantified intensity as well as unbearability of 69 symptoms with the State-of-Suffering-V (SOS-V). Also overall unbearable suffering was quantified. The five-point rating scale ranged from 1 (not at all) to 5 (hardly can be worse). For symptoms assessed to be unbearable the nature of the suffering was additionally investigated with open-ended questions. The final interviews were analyzed; for longitudinal evolvement also the pre-final interviews were analyzed. Symptom intensity scores 4 and 5 were defined to indicate high intensity. Symptom unbearability scores 4 and 5 were defined to indicate unbearable suffering. Two raters categorized the qualitative descriptions of unbearable suffering. Results Out of 148 requested patients 51% participated; 64 patients were followed up until death. The SOS-V was administered at least once in 60 patients (on average 30 days before death) and at least twice in 33 patients. Weakness was the most frequent unbearable symptom (57%). Pain was unbearable in 25%. Pain, loss of control over one’s life and fear of future suffering frequently were unbearable (89-92%) when symptom intensity was high. Loss of control over one’s life, vomiting and not being able to do important things frequently were unbearable (52-80%) when symptom intensity was low. Unbearable weakness significantly increased between pre-final and fina