Science.gov

Sample records for cancer profiles home

  1. Stemness-Related Transcriptional Factors and Homing Gene Expression Profiles in Hepatic Differentiation and Cancer

    PubMed Central

    Toraih, Eman A; Fawzy, Manal S; El-Falouji, Abdullah I; Hamed, Elham O; Nemr, Nader A; Hussein, Mohammad H; Fadeal, Noha M Abd El

    2016-01-01

    Stem cell transcriptional signature activation is an essential event in the development of cancer. This study aimed to investigate the differential expression profiles of three pluripotency-associated genes, OCT4, NANOG and SOX2, G-protein-coupled chemokine receptor 4 (CXCR4) and the ligand CXCL2, and alpha-fetoprotein (AFP) in hepatogenic differentiated stem cells and in sera of hepatitis C virus (HCV) and HCV-induced hepatocellular carcinoma (HCC) patients. Mesenchymal stem cells derived from umbilical cord blood were differentiated using hepatogenic differentiation media. Serum specimens were collected from 96 patients (32 cirrhotic HCV, 32 early HCC and 32 late HCC) and 96 controls. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed for relative quantification of the six target genes using the Livak method. In silico network analysis was also executed to explore the pluripotency and tumorigenetic regulatory circuits in liver cancer. The expression levels of all genes declined gradually during the stages of stem cell differentiation. On univariate and multivariate analyses, NANOG, CXCR4 and AFP were significantly upregulated in late clinical stage HCC patients. In contrast, SOX2 and CXCL2 were markedly overexpressed in cirrhotic patients and could be used for clear demarcation between cirrhotic and HCC patients in our cases. In conclusion, our data highlight the potential role of the SOX2 stem cell marker and CXCL2 chemokine in liver cell degeneration and fibrogenesis in HCV-induced hepatic cirrhosis in our sample of the Egyptian population. In addition, the significant association of NANOG and CXCR4 high expression with late HCC could contribute to the acquisition of stem cell–like properties in hepatic cancer and dissemination in late stages, respectively. Taken together, our results could have potential application in HCC prognosis and treatment. PMID:27623812

  2. 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…

  3. 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…

  4. 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.

  5. 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.

  6. 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.

  7. 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. |

  8. 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.

  9. Genetics Home Reference: bladder cancer

    MedlinePlus

    ... SA, James ND, Jankowski JA, Wallace DM. Molecular pathways in bladder cancer: part 1. BJU Int. 2005 Mar;95(4): ... SA, James ND, Jankowski JA, Wallace DM. Molecular pathways in bladder cancer: part 2. BJU Int. 2005 Mar;95(4): ...

  10. Genetics Home Reference: prostate cancer

    MedlinePlus

    ... genes. Others act as tumor suppressors through different pathways. Changes in these genes probably make only a small contribution to overall prostate cancer risk. However, researchers suspect that the combined influence ...

  11. Genetics Home Reference: breast cancer

    MedlinePlus

    ... a small or moderate contribution to overall breast cancer risk. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1 or BRCA2 genes. Others act through different pathways. Researchers suspect that the combined influence of variations ...

  12. Genetics Home Reference: lung cancer

    MedlinePlus

    ... present in up to half of all lung cancer cases. These genes each provide instructions for making a protein that is embedded within the cell membrane. When these proteins are turned on (activated) by binding to other molecules, signaling pathways are triggered within cells that promote cell growth ...

  13. Genetics Home Reference: ovarian cancer

    MedlinePlus

    ... a small or moderate contribution to overall ovarian cancer risk. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1 or BRCA2 genes. Others act through different pathways. Researchers suspect that the combined influence of variations ...

  14. "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.

  15. 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…

  16. Development of the Cancer Survivor Profile

    DTIC Science & Technology

    2014-05-09

    offering your experience and advice throughout this process. My deepest gratitude goes to my second reader, Dr. Neil Grunberg, for his encouragement and...Among women, the highest incidence of all cancers is breast cancer. While breast cancer is the second leading cause of cancer-related deaths in...morbidities (medical, psychological, behavior related) and to provide surveillance for recurrence or second cancers (216). The Cancer Survivor Profile

  17. 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.

  18. 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…

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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,

  4. 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

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Protease Profiling in Prostate Cancer

    DTIC Science & Technology

    2004-05-01

    acid synthase, which contains a serine hydrolase domain. We identified a lead inhibitor of this domain of fatty acid synthase, called Orlistat, which...SUBJECT TERMS 15. NUMBER OF PAGES Prostate cancer, tumor biology, protease, proteomics, transgenic, 20 animal model, fatty acid synthase, orlistat 16...the enzymes we identified is fatty acid synthase. Fatty acid synthase is the sole enzyme responsible for the cellular synthesis of fatty acids . This

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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…

  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. 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.

  4. 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

  5. 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.

  6. 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.

  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. 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.

  9. 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…

  10. 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

  11. 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.

  12. [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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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

  19. 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.

  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. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  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. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. [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.

  15. 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…

  16. 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…

  17. 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

  18. 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…

  19. 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

  20. 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…

  1. 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.

  2. 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.

  3. 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

  4. [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.

  5. 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.

  6. [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.

  7. 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:…

  8. 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…

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Expression and Genomic Profiling of Minute Breast Cancer Samples. Addendum

    DTIC Science & Technology

    2007-07-01

    gene expression profiling and Array-based Comparative Genomic Hybridization (array-CGH) offers global views of cancer genomes and transcriptomes by...gene expression measurements were made in Excel (Microsoft, Redmond, WA). Global Pearson correlation coefficients for microarrays were calculated...Pera, R.A. (2003) Feasibility of global gene expression analysis in testicular biopsies from infertile men. Mol Reprod Dev, 66, 403-421. 21

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. [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.

  3. 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.

  4. 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.

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

    DTIC Science & Technology

    2014-12-18

    1007 TITLE: Molecular Profiles for Lung Cancer Pathogenesis and Detection in U.S. Veterans PRINCIPAL INVESTIGATOR: Ignacio I. Wistuba, M.D...2014 2. REPORT TYPE Final 3. DATES COVERED 20 Sep 2010 - 19 Sep 2014 4. TITLE AND SUBTITLE Molecular Profiles for Lung Cancer Pathogenesis and...field cancerization in NSCLC; 3) identified gradient profiles in the localized field cancerization that embody the nearby lung tumors; 4) demonstrated

  6. 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

  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. 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

  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. 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.

  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. 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.

  16. 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

  17. 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

  18. 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

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... 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...

  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. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... 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...

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... 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...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... 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...

  3. 21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... 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...

  4. 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.

  5. [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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. [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.

  11. 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.

  12. [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.

  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. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

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

    PubMed Central

    Ashkani, Jahanshah; Naidoo, Kevin J.

    2016-01-01

    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. PMID:27198045

  3. 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.

  4. 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)

  5. 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…

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. [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.

  15. 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

  16. 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.

  17. 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

  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. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. [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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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

  15. Distinctive serum protein profiles involving abundant proteins in lung cancer patients based upon antibody microarray analysis

    PubMed Central

    Gao, Wei-Min; Kuick, Rork; Orchekowski, Randal P; Misek, David E; Qiu, Ji; Greenberg, Alissa K; Rom, William N; Brenner, Dean E; Omenn, Gilbert S; Haab, Brian B; Hanash, Samir M

    2005-01-01

    Background Cancer serum protein profiling by mass spectrometry has uncovered mass profiles that are potentially diagnostic for several common types of cancer. However, direct mass spectrometric profiling has a limited dynamic range and difficulties in providing the identification of the distinctive proteins. We hypothesized that distinctive profiles may result from the differential expression of relatively abundant serum proteins associated with the host response. Methods Eighty-four antibodies, targeting a wide range of serum proteins, were spotted onto nitrocellulose-coated microscope slides. The abundances of the corresponding proteins were measured in 80 serum samples, from 24 newly diagnosed subjects with lung cancer, 24 healthy controls, and 32 subjects with chronic obstructive pulmonary disease (COPD). Two-color rolling-circle amplification was used to measure protein abundance. Results Seven of the 84 antibodies gave a significant difference (p < 0.01) for the lung cancer patients as compared to healthy controls, as well as compared to COPD patients. Proteins that exhibited higher abundances in the lung cancer samples relative to the control samples included C-reactive protein (CRP; a 13.3 fold increase), serum amyloid A (SAA; a 2.0 fold increase), mucin 1 and α-1-antitrypsin (1.4 fold increases). The increased expression levels of CRP and SAA were validated by Western blot analysis. Leave-one-out cross-validation was used to construct Diagonal Linear Discriminant Analysis (DLDA) classifiers. At a cutoff where all 56 of the non-tumor samples were correctly classified, 15/24 lung tumor patient sera were correctly classified. Conclusion Our results suggest that a distinctive serum protein profile involving abundant proteins may be observed in lung cancer patients relative to healthy subjects or patients with chronic disease and may have utility as part of strategies for detecting lung cancer. PMID:16117833

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

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

    DTIC Science & Technology

    2014-12-01

    RNA -sequencing and microarray profiling of nasal epithelia, airway epithelial cells collected from both bronchoscopy and lobectomy specimens as well...lesions and epithelial components of the tumors. These cell populations are being profiled with RNA -seq to determine their gene expression...cancer. We have collected on 13 individuals with SCLC, isolated total RNA and were able to obtain quality RNA on 11 of them as shown in Table 3. The

  2. 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

  3. Traditional home-brewed beer consumption and iron status in patients with esophageal cancer and healthy control subjects from Transkei, South Africa.

    PubMed

    Matsha, Tandi; Brink, Lucy; van Rensburg, Susan; Hon, Dinie; Lombard, Carl; Erasmus, Rajiv

    2006-01-01

    Consumption of home-brewed beer is associated with dietary iron excess and a high incidence of esophageal cancer in Transkei, South Africa. We examined the relationship between home-brewed beer consumption and body iron status in 234 patients with esophageal squamous cell carcinoma and 595 control subjects residing in Transkei. Subjects were screened for iron overload using transferrin saturation >45%, and/or serum ferritin >200 microg/l for women and >300 microg/l for men. A questionnaire was administered to all subjects, and iron content of randomly selected home-brewed beer samples was determined. The iron content of home-brewed beer was 258-fold higher than the commercial Castle Lager beer produced by South African Breweries. The prevalence of home-brewed beer consumption was 30.1% in esophageal cancer patients and 15.5% in control subjects and was found not to be a risk factor for esophageal cancer after adjustment for age, sex, and tobacco consumption (male subjects, odds ratio= 1.6 (95% confidence interval [CI]: 0.7-4.5); female subjects, odds ratio=1.7 (95% CI: 0.7-4.5). Iron overload as determined by transferrin saturation and elevated serum ferritin was observed in 4.3% of patients with esophageal cancer and 0.7% of control subjects and was not associated with the consumption of home-brewed beer. Consumption of home-brewed beer is not a risk factor for esophageal cancer and is not linked with iron overload in either cancer patients or control subjects; however, iron overload is likely to result from a combination of dietary intake and a genetic component.

  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. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Expression and Genomic Profiling of Minute Breast Cancer Samples

    DTIC Science & Technology

    2006-07-01

    Array-based Comparative Genomic Hybridization (array-CGH) offers global views of cancer genomes and transcriptomes by detecting amplification or deletion...were made in Excel (Microsoft, Redmond, WA). Global Pearson correlation coefficients for microarrays were calculated using the statistical software...Feasibility of global gene expression analysis in testicular biopsies from infertile men. Mol Reprod Dev, 66, 403-421. 21. Papadopoulou, E., Davilas

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. [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.

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  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. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. High-throughput genomic profiling of adult solid tumors reveals novel insights into cancer pathogenesis.

    PubMed

    Hartmaier, Ryan J; Albacker, Lee; Chmielecki, Juliann; Bailey, Mark; He, Jie; Goldberg, Michael; Ramkissoon, Shakti; Suh, James; Elvin, Julia A; Chiacchia, Samuel; Frampton, Garrett M; Ross, Jeffrey S; Miller, Vincent; Stephens, Philip J; Lipson, Doron

    2017-02-24

    Genomic profiling is widely predicted to become a standard of care in clinical oncology, but more effective data sharing to accelerate progress in precision medicine will be required. Here we describe cancer-associated genomic profiles from 18,004 unique adult cancers. The dataset was composed of 162 tumor subtypes including multiple rare and uncommon tumors. Comparison of alteration frequencies to The Cancer Genome Atlas (TCGA) identified some differences and suggested an enrichment of treatment-refractory samples in breast and lung cancer cohorts. To illustrate novelty within the dataset, we surveyed the genomic landscape of rare diseases and identified an increased frequency of NOTCH1 alterations in adenoid cystic carcinomas compared to previous studies. Analysis of tumor suppressor gene patterns revealed disease specificity for certain genes but broad inactivation of others. We identified multiple potentially druggable, novel and known kinase fusions in diseases beyond those in which they are currently recognized. Analysis of variants of unknown significance identified an enrichment of SMAD4 alterations in colon cancer and other rare alterations predicted to have functional impact. Analysis of established, clinically relevant alterations highlighted the spectrum of molecular changes for which testing is currently recommended, as well as opportunities for expansion of indications for use of approved targeted therapies. Overall, this dataset presents a new resource with which to investigate rare alterations and diseases, validate clinical relevance, and identify novel therapeutic targets.

  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. 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.

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. Prostate cancer cells preferentially home to osteoblast-rich areas in the early stages of bone metastasis: evidence from in vivo models.

    PubMed

    Wang, Ning; Docherty, Freyja E; Brown, Hannah K; Reeves, Kimberley J; Fowles, Anne C M; Ottewell, Penelope D; Dear, T Neil; Holen, Ingunn; Croucher, Peter I; Eaton, Colby L

    2014-12-01

    It has been suggested that metastasis-initiating cells gain a foothold in bone by homing to a metastastatic microenvironment (or "niche"). Whereas the precise nature of this niche remains to be established, it is likely to contain bone cell populations including osteoblasts and osteoclasts. In the mouse tibia, the distribution of osteoblasts on endocortical bone surfaces is non-uniform, and we hypothesize that studying co-localization of individual tumor cells with resident cell populations will reveal the identity of critical cellular components of the niche. In this study, we have mapped the distribution of three human prostate cancer cell lines (PC3-NW1, LN-CaP, and C4 2B4) colonizing the tibiae of athymic mice following intracardiac injection and evaluated their interaction with potential metastatic niches. Prostate cancer cells labeled with the fluorescent cell membrane dye (Vybrant DiD) were found by two-photon microscopy to be engrafted in the tibiae in close proximity (∼40 µm) to bone surfaces and 70% more cancer cells were detected in the lateral compared to the medial endocortical bone regions. This was associated with a 5-fold higher number of osteoblasts and 7-fold higher bone formation rate on the lateral endocortical bone surface compared to the medial side. By disrupting cellular interactions mediated by the chemokine (C-X-C motif) receptor 4 (CXCR4)/chemokine ligand 12 (CXCL12) axis with the CXCR4 inhibitor AMD3100, the preferential homing pattern of prostate cancer cells to osteoblast-rich bone surfaces was disrupted. In this study, we map the location of prostate cancer cells that home to endocortical regions in bone and our data demonstrate that homing of prostate cancer cells is associated with the presence and activity of osteoblast lineage cells, and suggest that therapies targeting osteoblast niches should be considered to prevent development of incurable prostate cancer bone metastases.

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. Molecular profiling to identify molecular mechanism in esophageal cancer with familial clustering.

    PubMed

    Chattopadhyay, Indranil; Phukan, Rupkumar; Singh, Avninder; Vasudevan, Madavan; Purkayastha, Joydeep; Hewitt, Stephen; Kataki, Amal; Mahanta, Jagadish; Kapur, Sujala; Saxena, Sunita

    2009-05-01

    To identify the genes and molecular functional pathways involved in esophageal cancer, we analyzed the gene expression profile of esophageal tumor tissue from patients having family history of esophageal cancer by cDNA microarray. Three hundred and fifty differentially expressed genes (26 up-regulated and 324 down-regulated) were identified. Genes involved in humoral immune response (PF4), extracellular matrix organization (COL4A4), metabolism of xenobiotics (EPHX1), TGF-beta signaling (SMAD1) and calcium signaling pathways (VDAC1) were down-regulated and genes involved in regulation of actin cytoskeleton (WASL), neuroactive ligand receptor interaction (GRM3), Toll-like receptor (CD14), B-cell receptor (IFITM1) and insulin signaling pathways (FOXO1A) were up-regulated. Validation of differential expression of subset of genes by QRT-PCR and tissue microarray in familial and non-familial cases showed no significant difference in expression of these genes in two groups suggesting familial clustering occurs as result of sharing of common environmental factors. Gene expression profiling of clinical specimens from well characterized populations that have familial clustering of cancer identified molecular mechanism associated with progression of esophageal cancer.

  12. Circulating micro-RNA expression profiles in early stage nonsmall cell lung cancer.

    PubMed

    Heegaard, Niels H H; Schetter, Aaron J; Welsh, Judith A; Yoneda, Mitsuhiro; Bowman, Elise D; Harris, Curtis C

    2012-03-15

    Circulating micro-RNA (miR) profiles have been proposed as promising diagnostic and prognostic biomarkers for cancer, including lung cancer. We have developed methods to accurately and reproducibly measure micro-RNA levels in serum and plasma. Here, we study paired serum and plasma samples from 220 patients with early stage nonsmall cell lung cancer (NSCLC) and 220 matched controls. We use qRT-PCR to measure the circulating levels of 30 different miRs that have previously been reported to be differently expressed in lung cancer tissue. Duplicate RNA extractions were performed for 10% of all samples, and micro-RNA measurements were highly correlated among those duplicates. This demonstrates high reproducibility of our assay. The expressions of miR-146b, miR-221, let-7a, miR-155, miR-17-5p, miR-27a and miR-106a were significantly reduced in the serum of NSCLC cases, while miR-29c was significantly increased. No significant differences were observed in plasma of patients compared with controls. Overall, expression levels in serum did not correlate well with levels in plasma. In secondary analyses, reduced plasma expression of let-7b was modestly associated with worse cancer-specific mortality in all patients, and reduced serum expression of miR-223 was modestly associated with cancer-specific mortality in stage IA/B patients. MiR profiles also showed considerable differences comparing African American and European Americans. In summary, we found significant differences in miR expression when comparing cases and controls and find evidence that expression of let-7b is associated with prognosis in NSCLC.

  13. The Effect of Training and Monitoring at Home on the Knowledge Level and Practices of Married Women Regarding Breast and Cervical Cancer

    PubMed Central

    Kolutek, Rahşan; Avcı, İlknur Aydın

    2015-01-01

    Objective This study was performed as a semi-experimental study to determine the effects of training and monitoring at home on the knowledge level and practices of married women regarding breast and cervical cancer. Materials and Methods The research sample consisted of 153 women. Data was collected by the “Introductory Questionnaire” and “Breast Cancer and Cervical Cancer symptoms, prevention, early diagnosis information and application form.” After the data was collected, women received training. After training, to monitor changes, phone calls were made along with home visits for 6 months. After the end of the visits, forms were re-administered. For statistical analysis, the Shapiro–Wilk test, Friedman analysis, and Student–Newman–Keuls test were performed. Results According to the findings, women increased their score from the information form after planned monitoring at home, and the difference between the first and last measurement points was statistically significant (p<0.001). Similarly, it was found that women increased their score from the information form about cervical cancer, and the difference between the first and last measurement points was statistically significant (p<0.001). Conclusion At the end of the study, 84% of women were found to begin the application of breast self-examination (BSE). As a result, women’s knowledge concerning breast and cervical cancer has changed in a positive manner with planned monitoring and training.

  14. Multiparametric profiling of non–small-cell lung cancers reveals distinct immunophenotypes

    PubMed Central

    Lizotte, Patrick H.; Ivanova, Elena V.; Awad, Mark M.; Jones, Robert E.; Keogh, Lauren; Liu, Hongye; Dries, Ruben; Herter-Sprie, Grit S.; Santos, Abigail; Feeney, Nora B.; Paweletz, Cloud P.; Kulkarni, Meghana M.; Bass, Adam J.; Rustgi, Anil K.; Yuan, Guo-Cheng; Kufe, Donald W.; Jänne, Pasi A.; Hammerman, Peter S.; Sholl, Lynette M.; Hodi, F. Stephen; Richards, William G.; Bueno, Raphael; English, Jessie M.; Bittinger, Mark A.

    2016-01-01

    BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non–small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). RESULTS. Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of PD-1 and TIM-3 and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, approximately 20% of cases had high B cell infiltrates with a subset producing IL-10. CONCLUSIONS. Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. FUNDING. The Robert A. and Renée E. Belfer Family Foundation, Expect Miracles Foundation, Starr Cancer Consortium, Stand Up to Cancer Foundation, Conquer Cancer Foundation, International Association for the Study of Lung Cancer, National Cancer Institute (R01 CA205150), and the Damon Runyon Cancer Research Foundation. PMID:27699239

  15. Multiparametric profiling of non-small-cell lung cancers reveals distinct immunophenotypes.

    PubMed

    Lizotte, Patrick H; Ivanova, Elena V; Awad, Mark M; Jones, Robert E; Keogh, Lauren; Liu, Hongye; Dries, Ruben; Almonte, Christina; Herter-Sprie, Grit S; Santos, Abigail; Feeney, Nora B; Paweletz, Cloud P; Kulkarni, Meghana M; Bass, Adam J; Rustgi, Anil K; Yuan, Guo-Cheng; Kufe, Donald W; Jänne, Pasi A; Hammerman, Peter S; Sholl, Lynette M; Hodi, F Stephen; Richards, William G; Bueno, Raphael; English, Jessie M; Bittinger, Mark A; Wong, Kwok-Kin

    2016-09-08

    BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). RESULTS. Cytometric profiling identified an immunologically "hot" cluster with abundant CD8(+) T cells expressing high levels of PD-1 and TIM-3 and an immunologically "cold" cluster with lower relative abundance of CD8(+) T cells and expression of inhibitory markers. The "hot" cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the "hot" cluster. Additionally, approximately 20% of cases had high B cell infiltrates with a subset producing IL-10. CONCLUSIONS. Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. FUNDING. The Robert A. and Renée E. Belfer Family Foundation, Expect Miracles Foundation, Starr Cancer Consortium, Stand Up to Cancer Foundation, Conquer Cancer Foundation, International Association for the Study of Lung Cancer, National Cancer Institute (R01 CA205150), and the Damon Runyon Cancer Research Foundation.

  16. 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)

  17. Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles

    PubMed Central

    Marien, Eyra; Meister, Michael; Muley, Thomas; Fieuws, Steffen; Bordel, Sergio; Derua, Rita; Spraggins, Jeffrey; Van de Plas, Raf; Dehairs, Jonas; Wouters, Jens; Bagadi, Muralidhararao; Dienemann, Hendrik; Thomas, Michael; Schnabel, Philipp A; Caprioli, Richard M; Waelkens, Etienne; Swinnen, Johannes V

    2015-01-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer death globally. To develop better diagnostics and more effective treatments, research in the past decades has focused on identification of molecular changes in the genome, transcriptome, proteome, and more recently also the metabolome. Phospholipids, which nevertheless play a central role in cell functioning, remain poorly explored. Here, using a mass spectrometry (MS)-based phospholipidomics approach, we profiled 179 phospholipid species in malignant and matched non-malignant lung tissue of 162 NSCLC patients (73 in a discovery cohort and 89 in a validation cohort). We identified 91 phospholipid species that were differentially expressed in cancer versus non-malignant tissues. Most prominent changes included a decrease in sphingomyelins (SMs) and an increase in specific phosphatidylinositols (PIs). Also a decrease in multiple phosphatidylserines (PSs) was observed, along with an increase in several phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species, particularly those with 40 or 42 carbon atoms in both fatty acyl chains together. 2D-imaging MS of the most differentially expressed phospholipids confirmed their differential abundance in cancer cells. We identified lipid markers that can discriminate tumor versus normal tissue and different NSCLC subtypes with an AUC (area under the ROC curve) of 0.999 and 0.885, respectively. In conclusion, using both shotgun and 2D-imaging lipidomics analysis, we uncovered a hitherto unrecognized alteration in phospholipid profiles in NSCLC. These changes may have important biological implications and may have significant potential for biomarker development. What’s new? Cellular membranes are subject to extensive modification in cancer, often with marked alterations in phospholipid metabolism. The extent and nature of those changes are not fully known, however, particularly for non-small cell lung cancer (NSCLC). In this study, lipidomics analysis

  18. Gamma-Retrovirus Integration Marks Cell Type-Specific Cancer Genes: A Novel Profiling Tool in Cancer Genomics

    PubMed Central

    Gilroy, Kathryn L.; Terry, Anne; Naseer, Asif; de Ridder, Jeroen; Wang, Weiwei; Carpenter, Eric; Mason, Andrew; Wong, Gane K-S.; Kilbey, Anna; Neil, James C.

    2016-01-01

    Retroviruses have been foundational in cancer research since early studies identified proto-oncogenes as targets for insertional mutagenesis. Integration of murine gamma-retroviruses into the host genome favours promoters and enhancers and entails interaction of viral integrase with host BET/bromodomain factors. We report that this integration pattern is conserved in feline leukaemia virus (FeLV), a gamma-retrovirus that infects many human cell types. Analysis of FeLV insertion sites in the MCF-7 mammary carcinoma cell line revealed strong bias towards active chromatin marks with no evidence of significant post-integration growth selection. The most prominent FeLV integration targets had little overlap with the most abundantly expressed transcripts, but were strongly enriched for annotated cancer genes. A meta-analysis based on several gamma-retrovirus integration profiling (GRIP) studies in human cells (CD34+, K562, HepG2) revealed a similar cancer gene bias but also remarkable cell-type specificity, with prominent exceptions including a universal integration hotspot at the long non-coding RNA MALAT1. Comparison of GRIP targets with databases of super-enhancers from the same cell lines showed that these have only limited overlap and that GRIP provides unique insights into the upstream drivers of cell growth. These observations elucidate the oncogenic potency of the gamma-retroviruses and support the wider application of GRIP to identify the genes and growth regulatory circuits that drive distinct cancer types. PMID:27097319

  19. 6 Common Cancers - Colorectal Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Colorectal Cancer Past Issues / Spring 2007 Table of Contents For ... colon cancer. Photo: AP Photo/Ron Edmonds Colorectal Cancer Cancer of the colon (large intestine) or rectum ( ...

  20. 6 Common Cancers - Breast Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Breast Cancer Past Issues / Spring 2007 Table of Contents For ... her down. Photo: AP Photo/Brett Flashnick Breast Cancer Breast cancer is a malignant (cancerous) growth that ...

  1. Investigating Molecular Profiles of Ovarian Cancer: An Update on Cancer Stem Cells

    PubMed Central

    Tomao, Federica; Papa, Anselmo; Strudel, Martina; Rossi, Luigi; Lo Russo, Giuseppe; Benedetti Panici, Pierluigi; Ciabatta, Francesca Romana; Tomao, Silverio

    2014-01-01

    Currently we are more and more improving our knowledge about the characteristics and the role of cancer stem cells in human cancer. Particularly we have realized that self-renewing ovarian cancer stem cells (CSCs) or ovarian cancer-initiating cells, and mesenchymal stem cells (SCs) too, are probably implicated in the etiopathogenesis of epithelial ovarian cancer (EOC). There is clear evidence that these cells are also involved in its intra- and extra-peritoneal diffusion and in the occurrence of chemo-resistance. In assessing the molecular characteristics of ovarian CSCs, we have to take note that these cellular populations are rare and the absence of specific cell surface markers represents a challenge to isolate and identify pure SC populations. In our review, we focused our attention on the molecular characteristics of epithelial ovarian CSCs and on the methods to detect them starting from their biological features. The study of ovarian CSCs is taking on an increasingly important strategic role, mostly for the potential therapeutic application in the next future. PMID:24723972

  2. Extending Computer Technology to Hospice Research: Interactive Pentablet Measurement of Symptoms by Hospice Cancer Patients in Their Homes

    PubMed Central

    Kim, Young Ok; Suarez, Marie L.; Dauw, Colleen M.; Stapleton, Stephen J.; Gorman, Geraldine; Storfjell, Judith; Zhao, Zhongsheng

    2009-01-01

    Abstract We aimed to determine the acceptability and feasibility of a pentablet-based software program, PAINReportIt®-Plus, as a means for patients with cancer in home hospice to report their symptoms and differences in acceptability by demographic variables. Of the 131 participants (mean age = 59 ± 13, 58% women, 48.1% African American), 44% had never used a computer, but all participants easily used the computerized tool and reported an average computer acceptability score of 10.3 ± 1.8, indicating high acceptability. Participants required an average of 19.1 ± 9.5 minutes to complete the pain section, 9.8 ± 6.5 minutes for the medication section, and 4.8 ± 2.3 minutes for the symptom section. The acceptability scores were not statistically different by demographic variables but time to complete the tool differed by racial/ethnic groups. Our findings demonstrate that terminally ill patients with cancer are willing and able to utilize computer pentablet technology to record and describe their pain and other symptoms. Visibility of pain and distress is the first step necessary for the hospice team to develop a care plan for improving control of noxious symptoms. PMID:19594343

  3. Loneliness, loss, and social support among cognitively intact older people with cancer, living in nursing homes – a mixed-methods study

    PubMed Central

    Drageset, Jorunn; Eide, Geir Egil; Dysvik, Elin; Furnes, Bodil; Hauge, Solveig

    2015-01-01

    Background Loneliness is a significant psychosocial effect following a cancer diagnosis and may prevent people from engaging in social activities, thus creating difficulties in interpersonal relationships. This study investigated loneliness and social support among cognitively intact nursing home residents with cancer by using a quantitatively driven mixed-methods design with sequential supplementary qualitative components. Methods The quantitative component consisted of face-to-face interviews of 60 nursing home residents (≥65 years) using the one-item Loneliness Scale and the Social Provisions Scale. The supplementary psychosocial component consisted of qualitative research interviews about experiences related to loneliness with nine respondents. Results The quantitative results indicated that reassurance of worth was associated with loneliness. The experience of loneliness was identified by the following: loneliness that was dominated by a feeling of inner pain, feeling of loss, and feeling small. Loneliness was alleviated by the following: being engaged in activities, being in contact with other people, and occupying oneself. Conclusion Enhancing the lives of nursing home residents with cancer requires attending to the residents’ experience of loneliness and social relationships in a targeted and individualized manner. This might require screening all nursing home residents for early detection of loneliness. Revealing factors that may contribute to or reduce loneliness improves the ability to enhance people’s lives. PMID:26451093

  4. Global copy number profiling of cancer genomes | Office of Cancer Genomics

    Cancer.gov

    In this article, we introduce a robust and efficient strategy for deriving global and allele-specific copy number alternations (CNA) from cancer whole exome sequencing data based on Log R ratios and B-allele frequencies. Applying the approach to the analysis of over 200 skin cancer samples, we demonstrate its utility for discovering distinct CNA events and for deriving ancillary information such as tumor purity. Availability and implementation: https://github.com/xfwang/CLOSE CONTACT: xuefeng.wang@stonybrook.edu or michael.krauthammer@yale.edu. (Publication Abstract)

  5. PROFILES OF GENE EXPRESSION ASSOCIATED WITH TETRACYCLINE OVER EXPRESSION OF HSP70 IN MCF-7 BREAST CANCER CELLS

    EPA Science Inventory

    Profiles of gene expression associated with tetracycline over expression of HSP70 in MCF-7 breast cancer cells.

    Heat shock proteins (HSPs) protect cells from damage through their function as molecular chaperones. Some cancers reveal high levels of HSP70 expression in asso...

  6. Asbestos in the Home.

    ERIC Educational Resources Information Center

    Environmental Protection Agency, Washington, DC.

    The United States Government is concerned about asbestos-containing products in the home because sometimes asbestos fibers can be released from these produces. If asbestos fibers are inhaled, certain types of cancer may later develop. Asbestos in homes poses several problems. Household members have little or no protection from exposure to asbestos…

  7. No Place Like Home.

    ERIC Educational Resources Information Center

    Austin, Elizabeth

    2000-01-01

    To fight rampant consumerism (Martha Stewart Inc.), reduce the divorce rate, prevent cancer and heart disease, and ensure domestic tranquility, educators should bring back home economics. Workers must put more energy into the home front, and we must begin teaching our children how to live well on less. (MLH)

  8. Genetics Home Reference: neuroblastoma

    MedlinePlus

    ... Help Me Understand Genetics Home Health Conditions neuroblastoma neuroblastoma Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Neuroblastoma is a type of cancer that most often ...

  9. Serum metabolomic profiling of prostate cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial

    PubMed Central

    Huang, Jiaqi; Mondul, Alison M; Weinstein, Stephanie J; Koutros, Stella; Derkach, Andriy; Karoly, Edward; Sampson, Joshua N; Moore, Steven C; Berndt, Sonja I; Albanes, Demetrius

    2016-01-01

    Background: Two recent metabolomic analyses found serum lipid, energy, and other metabolites related to aggressive prostate cancer risk up to 20 years prior to diagnosis. Methods: We conducted a serum metabolomic investigation of prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that included annual serum total prostate-specific antigen measurement and digital rectal examination. This nested study included 380 cases diagnosed post-screening and 380 controls individually matched to cases on age, race, study centre, and blood-collection date (median time to diagnosis, 10 years (range 4.4–17 years)). Sera were analysed on a high-resolution accurate mass platform of ultrahigh-performance liquid and gas chromatography/mass spectroscopy that identified 695 known metabolites. Logistic regression conditioned on the matching factors estimated odds ratios (OR) and 95% confidence intervals of risk associated with an 80th percentile increase in the log-metabolite signal. Results: Twenty-seven metabolites were associated with prostate cancer at P<0.05. Pyroglutamine, gamma-glutamylphenylalanine, phenylpyruvate, N-acetylcitrulline, and stearoylcarnitine showed the strongest metabolite-risk signals (ORs=0.53, 0.51, 0.46, 0.58, and 1.74, respectively; 0.001⩽P⩽0.006). Findings were similar for aggressive disease (peptide chemical class, P=0.03). None of the P-values were below the threshold of Bonferroni correction, however. Conclusions: A unique metabolomic profile associated with post-screening prostate cancer is identified that differs from that in a previously studied, unscreened population. PMID:27673363

  10. English Second-Language Learners in Preschool: Profile Effects in Their English Abilities and the Role of Home Language Environment

    ERIC Educational Resources Information Center

    Paradis, Johanne; Kirova, Anna

    2014-01-01

    The objectives of this study were twofold: (1) Determine the English proficiency of English second-language learners (ELLs) at the end of preschool as referenced to monolingual norms, and in particular, to determine if they showed an asynchronous profile, that is, approached monolingual norms more closely for some linguistic sub-skills than…

  11. Effect of rosemary polyphenols on human colon cancer cells: transcriptomic profiling and functional enrichment analysis.

    PubMed

    Valdés, Alberto; García-Cañas, Virginia; Rocamora-Reverte, Lourdes; Gómez-Martínez, Angeles; Ferragut, José Antonio; Cifuentes, Alejandro

    2013-01-01

    In this work, the effect of rosemary extracts rich on polyphenols obtained using pressurized fluids was investigated on the gene expression of human SW480 and HT29 colon cancer cells. The application of transcriptomic profiling and functional enrichment analysis was done via two computational approaches, Ingenuity Pathway Analysis and Gene Set Enrichment Analysis. These two approaches were used for functional enrichment analysis as a previous step for a reliable interpretation of the data obtained from microarray analysis. Reverse transcription quantitative-PCR was used to confirm relative changes in mRNA levels of selected genes from microarrays. The selection of genes was based on their expression change, adjusted p value, and known biological function. According to genome-wide transcriptomics analysis, rosemary polyphenols altered the expression of ~4 % of the genes covered by the Affymetrix Human Gene 1.0ST chip in both colon cancer cells. However, only ~18 % of the differentially expressed genes were common to both cell lines, indicating markedly different expression profiles in response to the treatment. Differences in induction of G2/M arrest observed by rosemary polyphenols in the two colon adenocarcinoma cell lines suggest that the extract may be differentially effective against tumors with specific mutational pattern. From our results, it is also concluded that rosemary polyphenols induced a low degree of apoptosis indicating that other multiple signaling pathways may contribute to colon cancer cell death.

  12. Unique epigenetic gene profiles define human breast cancers with poor prognosis

    PubMed Central

    Peña-Llopis, Samuel; Wan, Yihong; Martinez, Elisabeth D.

    2016-01-01

    Epigenetic enzymes are at the nexus of cellular regulatory cascades and can drive cancer-specific deregulation at all stages of the oncogenic process, yet little is known about their prognostic value in human patients. Here, we used qRT-PCR to profile at high resolution the expression of fifty-five epigenetic genes in over one hundred human breast cancer samples and patient-matched benign tissues. We correlated expression patterns with clinical and histological parameters and validated our findings in two independent large patient cohorts (TCGA and METABRIC). We found that human breast malignancies have unique epigenetic profiles and cluster into epigenetic subgroups. A subset of epigenetic genes defined an Epigenetic Signature as an independent predictor of patient survival that outperforms triple negative status and other clinical variables. Our results also suggest that breast cancer grade, but not stage, is driven by transcriptional alterations of epigenetic modifiers. Overall, this study uncovers the presence of epigenetic subtypes within human mammary malignancies and identifies tumor subgroups with specific pharmacologically targetable epigenetic susceptibilities not yet therapeutically exploited. PMID:27863398

  13. Transcript Profiling Distinguishes Complete Treatment Responders With Locally Advanced Cervical Cancer1234

    PubMed Central

    Fernandez-Retana, Jorge; Lasa-Gonsebatt, Federico; Lopez-Urrutia, Eduardo; Coronel-Martínez, Jaime; Cantu De Leon, David; Jacobo-Herrera, Nadia; Peralta-Zaragoza, Oscar; Perez-Montiel, Delia; Reynoso-Noveron, Nancy; Vazquez-Romo, Rafael; Perez-Plasencia, Carlos

    2015-01-01

    Cervical cancer (CC) mortality is a major public health concern since it is the second cause of cancer-related deaths among women. Patients diagnosed with locally advanced CC (LACC) have an important rate of recurrence and treatment failure. Conventional treatment for LACC is based on chemotherapy and radiotherapy; however, up to 40% of patients will not respond to conventional treatment; hence, we searched for a prognostic gene signature able to discriminate patients who do not respond to the conventional treatment employed to treat LACC. Tumor biopsies were profiled with genome-wide high-density expression microarrays. Class prediction was performed in tumor tissues and the resultant gene signature was validated by quantitative reverse transcription–polymerase chain reaction. A 27-predictive gene profile was identified through its association with pathologic response. The 27-gene profile was validated in an independent set of patients and was able to distinguish between patients diagnosed as no response versus complete response. Gene expression analysis revealed two distinct groups of tumors diagnosed as LACC. Our findings could provide a strategy to select patients who would benefit from neoadjuvant radiochemotherapy-based treatment. PMID:25926073

  14. Transcript profiling distinguishes complete treatment responders with locally advanced cervical cancer.

    PubMed

    Fernandez-Retana, Jorge; Lasa-Gonsebatt, Federico; Lopez-Urrutia, Eduardo; Coronel-Martínez, Jaime; Cantu De Leon, David; Jacobo-Herrera, Nadia; Peralta-Zaragoza, Oscar; Perez-Montiel, Delia; Reynoso-Noveron, Nancy; Vazquez-Romo, Rafael; Perez-Plasencia, Carlos

    2015-04-01

    Cervical cancer (CC) mortality is a major public health concern since it is the second cause of cancer-related deaths among women. Patients diagnosed with locally advanced CC (LACC) have an important rate of recurrence and treatment failure. Conventional treatment for LACC is based on chemotherapy and radiotherapy; however, up to 40% of patients will not respond to conventional treatment; hence, we searched for a prognostic gene signature able to discriminate patients who do not respond to the conventional treatment employed to treat LACC. Tumor biopsies were profiled with genome-wide high-density expression microarrays. Class prediction was performed in tumor tissues and the resultant gene signature was validated by quantitative reverse transcription-polymerase chain reaction. A 27-predictive gene profile was identified through its association with pathologic response. The 27-gene profile was validated in an independent set of patients and was able to distinguish between patients diagnosed as no response versus complete response. Gene expression analysis revealed two distinct groups of tumors diagnosed as LACC. Our findings could provide a strategy to select patients who would benefit from neoadjuvant radiochemotherapy-based treatment.

  15. Metabolic profiling in colorectal cancer reveals signature metabolic shifts during tumorigenesis.

    PubMed

    Ong, Eng Shi; Zou, Li; Li, Shaoxia; Cheah, Peh Yean; Eu, Kong Weng; Ong, Choon Nam

    2010-02-10

    Colorectal cancer (CRC) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor, and thus is an useful model for studying metabolic shift. In the present study, we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC. Colonic tissues including tumor, polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study. The metabolic profiles were obtained using GC/MS and LC/MS/MS. Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues. Various amino acids and lipids in the polyps and tumors were elevated, suggesting higher energy needs for increased cellular proliferation. In contrast, significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis. In addition, the accumulation of hypoxanthine and xanthine, and the decrease of uric acid concentration, suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC. Further, there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors. It appears that to gain a growth advantage, cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment.

  16. Cervical cancer screening with clinic-based Pap test versus home HPV test among Somali immigrant women in Minnesota: a pilot randomized controlled trial

    PubMed Central

    Sewali, Barrett; Okuyemi, Kolawole S; Askhir, Asli; Belinson, Jerome; Vogel, Rachel I; Joseph, Anne; Ghebre, Rahel G

    2015-01-01

    Cervical cancer is more common in the Somali immigrant population than the general population in the United States (US). There are low rates of cervical cancer screening among Somali women. This study compares cervical cancer screening test completion rates for a home human papilloma virus (HPV) test and standard clinic Pap test. Sixty-three Somali immigrant women aged 30–70 years who had not undergone cervical cancer screening within the past 3 years were randomly assigned to a home HPV test group (intervention) or a clinic Pap test group (control). Test completion rates were measured at 3 months. Univariate and multivariate logistic regression models were used to explore factors associated with test completion (intention-to-treat analysis). Participants in the HPV test group were 14 times more likely to complete the test compared to those in the Pap test group (P = 0.0002). Women who reported having friends/family members to talk about cancer screening were approximately three times more likely to complete any screening test than those who did not (P = 0.127) and participants who reported residing in the US longer were more likely to complete a screening test (P = 0.011). Future research should explore the potential of using the home-based HPV test kits as an initial approach to cervical cancer screening. Impact: The use of a self-sampling HPV kit has the potential to increase cervical cancer screening in under-served communities in the US. PMID:25653188

  17. Plasmonic Nanoparticle-based Hybrid Photosensitizers with Broadened Excitation Profile for Photodynamic Therapy of Cancer Cells

    NASA Astrophysics Data System (ADS)

    Wang, Peng; Tang, Hong; Zhang, Peng

    2016-10-01

    Photodynamic therapy combining nanotechnology has shown great potential with improved therapeutic efficacy and fewer side effects. Ideal photosensitizers for cancer treatment should both have good singlet oxygen production capability and be excitable by light illuminations with deep tissue penetration. Here we report a type of hybrid photosensitizers consisting of plasmonic silver nanoparticles and photosensitizing molecules, where strong resonance coupling between the two leads to a broadened excitation profile and exceptionally high singlet oxygen production under both visible light and infrared light excitations. Our results indicate that the hybrid photosensitizers display low cytotoxicity without light illumination yet highly enhanced photodynamic inhibition efficacy against Hela cells under a broad spectrum of light illuminations including the near-infrared light, which has great implication in photodynamic therapy of deep-tissue cancers.

  18. Plasmonic Nanoparticle-based Hybrid Photosensitizers with Broadened Excitation Profile for Photodynamic Therapy of Cancer Cells

    PubMed Central

    Wang, Peng; Tang, Hong; Zhang, Peng

    2016-01-01

    Photodynamic therapy combining nanotechnology has shown great potential with improved therapeutic efficacy and fewer side effects. Ideal photosensitizers for cancer treatment should both have good singlet oxygen production capability and be excitable by light illuminations with deep tissue penetration. Here we report a type of hybrid photosensitizers consisting of plasmonic silver nanoparticles and photosensitizing molecules, where strong resonance coupling between the two leads to a broadened excitation profile and exceptionally high singlet oxygen production under both visible light and infrared light excitations. Our results indicate that the hybrid photosensitizers display low cytotoxicity without light illumination yet highly enhanced photodynamic inhibition efficacy against Hela cells under a broad spectrum of light illuminations including the near-infrared light, which has great implication in photodynamic therapy of deep-tissue cancers. PMID:27725746

  19. Comparison of biodistribution profile of monoclonal antibodies nanoparticles and aptamers in rats with breast cancer.

    PubMed

    Cerqueira-Coutinho, Cristal; Missailidis, Sotiris; Alessandra-Perini, Jéssica; Machado, Daniel Escorsim; Perini, Jamila Alessandra; Santos-Oliveira, Ralph

    2017-05-01

    The use of monoclonal antibodies and aptamers is growing every single day, as the use of nanoparticle systems. Although most of the products are under investigation, there are a few commercialized products available at the market, for human consume. In this study, we have compared three formulations (aptamer anti-MUC1, monoclonal antibody - Trastuzumab and monoclonal antibodies nanoparticles - PLA/PVA/MMT trastuzumab) to identify their profile as also to understand their behavior into an alive biological system. In this direction the radiolabeling of the products were done and they were all tested in animals (in vivo) in two conditions: healthy rats and breast cancer induced animals. The results showed that the nanoparticle has the better biodistribution profile, followed by the aptamer. We conclude that more studies and a global effort to elucidate the biological behavior of drugs and especially nano-drugs are necessary.

  20. Molecular profiling in the treatment of colorectal cancer: focus on regorafenib

    PubMed Central

    Yan, Yiyi; Grothey, Axel

    2015-01-01

    Metastatic colorectal cancer (mCRC) is a highly heterogeneous disease. Its treatment outcome has been significantly improved over the last decade with the incorporation of biological targeted therapies, including anti-EGFR antibodies, cetuximab and panitumumab, and VEGF inhibitors, bevacizumab, ramucirumab, and aflibercept. The identification of predictive biomarkers has further improved the survival by accurately selecting patients who are most likely to benefit from these treatments, such as RAS mutation profiling for EGFR antibodies. Regorafenib is a multikinase inhibitor currently used as late line therapy for mCRC. The molecular and genetic markers associated with regorafenib treatment response are yet to be characterized. Here, we review currently available clinical evidence of mCRC molecular profiling, such as RAS, BRAF, and MMR testing, and its role in targeted therapies with special focus on regorafenib treatment. PMID:26508880

  1. MicroRNA-200 Family Profile: A Promising Ancillary Tool for Accurate Cancer Diagnosis.

    PubMed

    Liu, Xiaodong; Zhang, Jianhua; Xie, Botao; Li, Hao; Shen, Jihong; Chen, Jianheng

    2016-01-01

    Cancer is one of the most threatening diseases in the world and great interests have been paid to discover accurate and noninvasive methods for cancer diagnosis. The value of microRNA-200 (miRNA-200, miR-200) family has been revealed in many studies. However, the results from various studies were inconsistent, and thus a meta-analysis was designed and performed to assess the overall value of miRNA200 in cancer diagnosis. Relevant studies were searched electronically from the following databases: PubMed, Embase, Web of Science, the Cochrane Library, and Chinese National Knowledge Infrastructure. Keyword combined with "miR-200," "cancer," and "diagnosis" in any fields was used for searching relevant studies. Then, the pooled sensitivity, specificity, area under the curve (AUC), and partial AUC were calculated using the random-effects model. Heterogeneity among individual studies was also explored by subgroup analyses. A total of 28 studies from 18 articles with an overall sample size of 3676 subjects (2097 patients and 1579 controls) were included in this meta-analysis. The overall sensitivity and specificity with 95% confidence intervals (95% CIs) are 0.709 (95% CI: 0.657-0.755) and 0.667 (95% CI: 0.617-0.713), respectively. Additionally, AUC and partial AUC for the pooled data is 0.735 and 0.627, respectively. Subgroup analyses revealed that using miRNA-200 family for cancer diagnosis is more effective in white than in Asian ethnic groups. In addition, cancer diagnosis by miRNA using circulating specimen is more effective than that using noncirculating specimen. Finally, miRNA is more accurate in diagnosing endometrial cancer than other types of cancer, and some miRNA family members (miR-200b and miR-429) have superior diagnostic accuracy than other miR-200 family members. In conclusion, the profiling of miRNA-200 family is likely to be a valuable tool in cancer detection and diagnosis.

  2. Protein Profiling Gastric Cancer and Neighboring Control Tissues Using High-Content Antibody Microarrays

    PubMed Central

    Sill, Martin; Schröder, Christoph; Shen, Ying; Marzoq, Aseel; Komel, Radovan; Hoheisel, Jörg D.; Nienhüser, Henrik; Schmidt, Thomas; Kastelic, Damjana

    2016-01-01

    In this study, protein profiling was performed on gastric cancer tissue samples in order to identify proteins that could be utilized for an effective diagnosis of this highly heterogeneous disease and as targets for therapeutic approaches. To this end, 16 pairs of postoperative gastric adenocarcinomas and adjacent non-cancerous control tissues were analyzed on microarrays that contain 813 antibodies targeting 724 proteins. Only 17 proteins were found to be differentially regulated, with much fewer molecules than the numbers usually identified in studies comparing tumor to healthy control tissues. Insulin-like growth factor-binding protein 7 (IGFBP7), S100 calcium binding protein A9 (S100A9), interleukin-10 (IL‐10) and mucin 6 (MUC6) exhibited the most profound variations. For an evaluation of the proteins’ capacity for discriminating gastric cancer, a Receiver Operating Characteristic curve analysis was performed, yielding an accuracy (area under the curve) value of 89.2% for distinguishing tumor from non-tumorous tissue. For confirmation, immunohistological analyses were done on tissue slices prepared from another cohort of patients with gastric cancer. The utility of the 17 marker proteins, and particularly the four molecules with the highest specificity for gastric adenocarcinoma, is discussed for them to act as candidates for diagnosis, even in serum, and targets for therapeutic approaches. PMID:27600085

  3. [Epidemiological and biologic profile of breast cancer in Fez-Boulemane, Morocco].

    PubMed

    Abbass, F; Bennis, S; Znati, K; Akasbi, Y; Amrani, J K; El Mesbahi, O; Amarti, A

    2011-12-01

    In a retrospective study of 265 patients with breast cancer over 3 years (January 2007-September 2009) we examined the epidemiological profile of breast cancer to determine the impact of biological and prognostic factors on survival over 3 years and on the epidemiology of this cancer. Estrogen (RE), progesterone (RP) and human epidermal growth factor receptors (HER2) were evaluated and RE/RP/HER2 status determined. The patients were young (median age 45 years). Invasive tumours were found in 95.5% of the women. The average tumour size was big [3.6 (SD 2.6) cm] and only 14% were histological grade 1. Large tumour size and high histological grade were independent of patient's age. Overall survival at 3 years was only 49% for the RE-/RP-/HER2- subtype and 75% for the RE-/RP-/HER2+ subtype, while it was 96% for the RE+/RP+/HER2- subtype. The young age, large tumour size and high histological grade in our population suggest a lack of awareness of women about breast cancer.

  4. Gene expression profiling and non-small-cell lung cancer: where are we now?

    PubMed

    Santos, Edgardo S; Blaya, Marcelo; Raez, Luis E

    2009-05-01

    Despite new developments in molecular techniques and better knowledge on lung cancer tumor biology, many genetic alterations associated with the development and progression of lung carcinogenesis still remain unclear. Although the development of targeted agents has improved response rates and survival, lung cancer has a very high mortality rate, even for early stages. Thus, there is a greater need for other mechanisms or technologies that may help us diagnose, predict, and treat patients with lung cancer in a more effective way. One of these technologies has been the use of genomics. Some of the available genomic technologies include single-nucleotide polymorphism analysis, high-throughput capillary sequencing, serial analysis of gene expression, and gene expression arrays. DNA microarray analysis is capable of discovering changes in DNA expression within the neoplastic tumor. Thus, gene expression array could help us to decipher the complexity and interaction of different oncogenic pathways and, hence, could contribute to the selection of better targeted agents on an individual basis rather than a general and nonspecific approach as it has been done for many decades. Several studies initiated a few years ago have started to produce fruitful results. Herein, we review the role of gene expression profiling in lung cancer as a diagnostic tool, predictive and prognostic biomarker, and its potential use for a "personalized" medicine in the years to come.

  5. Comparative metabolic and lipidomic profiling of human breast cancer cells with different metastatic potentials

    PubMed Central

    Kim, So-Hyun; Kwon, Yeo-Jung; Chun, Young-Jin; Choi, Hyung-Kyoon

    2016-01-01

    This study conducted comprehensive and comparative metabolic and lipidomic profiling of a human epithelial breast cell line (MCF-10A), a slightly metastatic (MCF-7), and a highly metastatic (MDA-MB-231) breast cancer cell line using gas chromatography mass spectrometry (GC-MS) and direct infusion mass spectrometry (DI-MS). Among 39 metabolites identified by GC-MS analysis, xanthine, glucose-6-phosphate, mannose-6-phosphate, guanine, and adenine were selected as prognostic markers of breast cancer metastasis. Major metabolic pathways involved in differentiation of the cell lines were alanine, aspartate, and glutamate metabolism, purine metabolism and glycine, serine, and threonine metabolism. Among 44 intact lipid species identified by DI-MS analysis, the levels of most phospholipids were higher in both metastatic groups than in normal cells. Specifically, the levels of phosphatidylserine (PS) 18:0/20:4, phosphatidylinositol (PI) 18:0/20:4, and phosphatidylcholine (PC) 18:0/20:4 were markedly higher while those of phosphatidylethanolamine (PE) 18:1/18:1 and PI 18:0/18:1 were lower in MDA-MB-231 cells than in MCF-7 cells. A partial-least-squares regression model was developed and validated for predicting the metastatic potential of breast cancer cells. The information obtained in this study will be useful when developing diagnostic tools and for identifying potential therapeutic targets for metastatic breast cancer. PMID:27564096

  6. MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer.

    PubMed

    Huo, Lei; Wang, Yan; Gong, Yun; Krishnamurthy, Savitri; Wang, Jing; Diao, Lixia; Liu, Chang-Gong; Liu, Xiuping; Lin, Feng; Symmans, William F; Wei, Wei; Zhang, Xinna; Sun, Li; Alvarez, Ricardo H; Ueno, Naoto T; Fouad, Tamer M; Harano, Kenichi; Debeb, Bisrat G; Wu, Yun; Reuben, James; Cristofanilli, Massimo; Zuo, Zhuang

    2016-04-01

    Inflammatory breast cancer is the most aggressive form of breast cancer. Identifying new biomarkers to be used as therapeutic targets is in urgent need. Messenger RNA expression profiling studies have indicated that inflammatory breast cancer is a transcriptionally heterogeneous disease, and specific molecular targets for inflammatory breast cancer have not been well established. We performed microRNA expression profiling in inflammatory breast cancer in comparison with locally advanced noninflammatory breast cancer in this study. Although many microRNAs were differentially expressed between normal breast tissue and tumor tissue, most of them did not show differential expression between inflammatory and noninflammatory tumor samples. However, by microarray analysis, quantitative reverse transcription PCR, and in situ hybridization, we showed that microRNA-205 expression was decreased not only in tumor compared with normal breast tissue, but also in inflammatory breast cancer compared with noninflammatory breast cancer. Lower expression of microRNA-205 correlated with worse distant metastasis-free survival and overall survival in our cohort. A small-scale immunohistochemistry analysis showed coexistence of decreased microRNA-205 expression and decreased E-cadherin expression in some ductal tumors. MicroRNA-205 may serve as a therapeutic target in advanced breast cancer including inflammatory breast cancer.

  7. Large-scale pharmacological profiling of 3D tumor models of cancer cells

    PubMed Central

    Mathews Griner, Lesley A; Zhang, Xiaohu; Guha, Rajarshi; McKnight, Crystal; Goldlust, Ian S; Lal-Nag, Madhu; Wilson, Kelli; Michael, Sam; Titus, Steve; Shinn, Paul; Thomas, Craig J; Ferrer, Marc

    2016-01-01

    The discovery of chemotherapeutic agents for the treatment of cancer commonly uses cell proliferation assays in which cells grow as two-dimensional (2D) monolayers. Compounds identified using 2D monolayer assays often fail to advance during clinical development, most likely because these assays do not reproduce the cellular complexity of tumors and their microenvironment in vivo. The use of three-dimensional (3D) cellular systems have been explored as enabling more predictive in vitro tumor models for drug discovery. To date, small-scale screens have demonstrated that pharmacological responses tend to differ between 2D and 3D cancer cell growth models. However, the limited scope of screens using 3D models has not provided a clear delineation of the cellular pathways and processes that differentially regulate cell survival and death in the different in vitro tumor models. Here we sought to further understand the differences in pharmacological responses between cancer tumor cells grown in different conditions by profiling a large collection of 1912 chemotherapeutic agents. We compared pharmacological responses obtained from cells cultured in traditional 2D monolayer conditions with those responses obtained from cells forming spheres versus cells already in 3D spheres. The target annotation of the compound library screened enabled the identification of those key cellular pathways and processes that when modulated by drugs induced cell death in all growth conditions or selectively in the different cell growth models. In addition, we also show that many of the compounds targeting these key cellular functions can be combined to produce synergistic cytotoxic effects, which in many cases differ in the magnitude of their synergism depending on the cellular model and cell type. The results from this work provide a high-throughput screening framework to profile the responses of drugs both as single agents and in pairwise combinations in 3D sphere models of cancer cells. PMID

  8. MicroRNA profile in very young women with breast cancer

    PubMed Central

    2014-01-01

    Background Breast cancer is rarely diagnosed in very young women (35years old or younger), and it often presents with distinct clinical-pathological features related to a more aggressive phenotype and worse prognosis when diagnosed at this early age. A pending question is whether breast cancer in very young women arises from the deregulation of different underlying mechanisms, something that will make this disease an entity differentiated from breast cancer diagnosed in older patients. Methods We performed a comprehensive study of miRNA expression using miRNA Affymetrix2.0 array on paraffin-embedded tumour tissue of 42 breast cancer patients 35 years old or younger, 17 patients between 45 and 65 years old and 29 older than 65 years. Data were statistically analyzed by t-test and a hierarchical clustering via average linkage method was conducted. Results were validated by qRT-PCR. Putative targeted pathways were obtained using DIANA miRPath online software. Results The results show a differential and unique miRNA expression profile of 121 miRNAs (p-value <0.05), 96 of those with a FDR-value <0.05. Hierarchical clustering grouped the samples according to their age, but not by subtype nor by tumour characteristics. We were able to validate by qRT-PCR differences in the expression of 6 miRNAs: miR-1228*, miR-3196, miR-1275, miR-92b, miR-139 and miR-1207. Moreover, all of the miRNAs maintained the expression trend. The validated miRNAs pointed out pathways related to cell motility, invasion and proliferation. Conclusions The study suggests that breast cancer in very young women appears as a distinct molecular signature. To our knowledge, this is the first time that a validated microRNA profile, distinctive to breast cancer in very young women, has been presented. The miRNA signature may be relevant to open an important field of research in order to elucidate the underlying mechanism in this particular disease, which in a more clinical setting, could potentially help to

  9. [Home visiting nursing care for a terminal stage cancer patient with bed sore--coordination through exchanging of advice request memo as a useful tool].

    PubMed

    Sugihara, Sachiko; Yamada, Mai; Tayoshi, Mayumi; Kitamikado, Hatsue; Nakajima, Kazuyo; Konno, Hitomi; Akaeda, Kazuko; Yagishita, Toshiyuki; Oka, Yoichi

    2010-12-01

    Visiting nursing care service was provided to a 40s female patient, who had a terminal cancer with bed sore around the sacred bones. We started the nursing service when the patient was still cared at hospital. The nursing service we provided was coordinated by the certified nurse specialized in skin and excrement care and home visiting nurse. A smooth home care transition was resulted because of the coordination provided by the two nurses. We started coaching the family while the patient was still at the hospital with a home care instruction manual until the patient was discharged. All in all, the patient and her family were at ease with two nurses' coordinated efforts. Since the patient was cared at home, her bed sore problem got worse due to an absence of caregiver. In order to solve the bed sore problem, the visiting nurse took pictures of peeled adhesive patch and the bed sore around the sacred bones to show and consult with the certified nurse. With the advice from the certified nurse, the home visiting nurse was able to care the bed sore problem manageable in size. From this experience, we learned that a proper communication channel, in this case an advice request memo exchange, between the certified nurse and visiting nurse was a useful tool for both sides in order to properly assess the patient's medical care needs.

  10. Cost profiles of colorectal cancer patients in Italy based on individual patterns of care

    PubMed Central

    2013-01-01

    Background Due to changes in cancer-related risk factors, improvements in diagnostic procedures and treatments, and the aging of the population, in most developed countries cancer accounts for an increasing proportion of health care expenditures. The analysis of cancer-related costs is a topic of several economic and epidemiological studies and represents a research area of great interest to public health planners and policy makers. In Italy studies are limited either to some specific types of expenditures or to specific groups of cancer patients. Aim of the paper is to estimate the distribution of cancer survivors and associated health care expenditures according to a disease pathway which identifies three clinically relevant phases: initial (one year following diagnosis), continuing (between initial and final) and final (one year before death). Methods The methodology proposed is based on the reconstruction of patterns of care at individual level by combining different data sources, surveillance data and administrative data, in areas covered by cancer registration. Results A total colorectal cancer-related expenditure of 77.8 million Euros for 18012 patients (corresponding to about 4300 Euros per capita) is estimated in 2006 in two Italian areas located in Tuscany and Veneto regions, respectively. Cost of care varies according to the care pathway: 11% of patients were in the initial phase, and consumed 34% of total expenditure; patients in the final (6%) and in the continuing (83%) phase consumed 23% and 43% of the budget, respectively. There is an association between patterns of care/costs and patients characteristics such as stage and age at diagnosis. Conclusions This paper represents the first attempt to attribute health care expenditures in Italy to specific phases of disease, according to varying treatment approaches, surveillance strategies and management of relapses, palliative care. The association between stage at diagnosis, profile of therapies and

  11. Clinical impact of pharmacogenetic profiling with a clinical decision support tool in polypharmacy home health patients: A prospective pilot randomized controlled trial

    PubMed Central

    Henderson, John C.; Neradilek, Moni B.; Moyer, Nicolas A.; Ashcraft, Kristine C.; Thirumaran, Ranjit K.

    2017-01-01

    Background In polypharmacy patients under home health management, pharmacogenetic testing coupled with guidance from a clinical decision support tool (CDST) on reducing drug, gene, and cumulative interaction risk may provide valuable insights in prescription drug treatment, reducing re-hospitalization and emergency department (ED) visits. We assessed the clinical impact of pharmacogenetic profiling integrating binary and cumulative drug and gene interaction warnings on home health polypharmacy patients. Methods and findings This prospective, open-label, randomized controlled trial was conducted at one hospital-based home health agency between February 2015 and February 2016. Recruitment came from patient referrals to home health at hospital discharge. Eligible patients were aged 50 years and older and taking or initiating treatment with medications with potential or significant drug-gene-based interactions. Subjects (n = 110) were randomized to pharmacogenetic profiling (n = 57). The study pharmacist reviewed drug-drug, drug-gene, and cumulative drug and/or gene interactions using the YouScript® CDST to provide drug therapy recommendations to clinicians. The control group (n = 53) received treatment as usual including pharmacist guided medication management using a standard drug information resource. The primary outcome measure was the number of re-hospitalizations and ED visits at 30 and 60 days after discharge from the hospital. The mean number of re-hospitalizations per patient in the tested vs. untested group was 0.25 vs. 0.38 at 30 days (relative risk (RR), 0.65; 95% confidence interval (CI), 0.32–1.28; P = 0.21) and 0.33 vs. 0.70 at 60 days following enrollment (RR, 0.48; 95% CI, 0.27–0.82; P = 0.007). The mean number of ED visits per patient in the tested vs. untested group was 0.25 vs. 0.40 at 30 days (RR, 0.62; 95% CI, 0.31–1.21; P = 0.16) and 0.39 vs. 0.66 at 60 days (RR, 0.58; 95% CI, 0.34–0.99; P = 0.045). Differences in composite outcomes at

  12. Distinct Gene Expression Profiles of Proximal and Distal Colorectal Cancer: Implications for Cytotoxic and Targeted Therapy

    PubMed Central

    Maus, Martin K.H.; Hanna, Diana L.; Stephens, Craig L.; Astrow, Stephanie H.; Yang, Dongyun; Grimminger, Peter P.; Loupakis, Fotios; Hsiang, Jack H.; Zeger, Gary; Wakatsuki, Takeru; Barzi, Afsaneh; Lenz, Heinz-Josef

    2014-01-01

    Colorectal cancer (CRC) is a heterogeneous disease with genetic profiles and clinical outcomes dependent on the anatomic location of the primary tumor. How location impacts the molecular makeup of a tumor and how prognostic and predictive biomarkers differ between proximal versus distal colon cancers is not well established. We investigated the associations between tumor location, KRAS and BRAF mutation status, and the mRNA expression of proteins involved in major signaling pathways, including tumor growth (EGFR), angiogenesis (VEGFR2), DNA repair (ERCC1) and fluoropyrimidine metabolism (TS). FFPE tumor specimens from 431 advanced CRC patients were analyzed. The presence of 7 different KRAS base substitutions and the BRAF V600E mutation was determined. ERCC1, TS, EGFR and VEGFR2 mRNA expression levels were detected by RT-PCR. BRAF mutations were significantly more common in the proximal colon (p<0.001), whereas KRAS mutations occurred at similar frequencies throughout the colorectum. Rectal cancers had significantly higher ERCC1 and VEGFR2 mRNA levels compared to distal and proximal colon tumors (p=0.001), and increased TS levels compared to distal colon cancers (p=0.02). Mutant KRAS status was associated with lower ERCC1, TS, EGFR, and VEGFR2 gene expression in multivariate analysis. In a subgroup analysis, this association remained significant for all genes in the proximal colon and for VEGFR2 expression in rectal cancers. The mRNA expression patterns of predictive and prognostic biomarkers as well as associations with KRAS and BRAF mutation status depend on primary tumor location. Prospective studies are warranted to confirm these findings and determine the underlying mechanisms. PMID:25532759

  13. Predicting risk of breast cancer recurrence using gene-expression profiling.

    PubMed

    Ignatiadis, Michail; Desmedt, Christine

    2007-01-01

    The molecular profiling of breast tumors using the powerful microarray technology has uncovered the molecular heterogeneity of breast tumors and has offered novel insight into breast tumorigenesis. The estrogen receptor (ER) has been shown to be the most important discriminator dichotomizing breast cancer into two main subsets. At the same time, proliferation, as captured by the recently developed Genomic Grade Index (GGI) has been found to be the most important prognostic factor in breast cancer, far beyond ER status. Interestingly, this index encompasses a significant portion of the predictive power of many published prognostic signatures. The challenge now is to integrate all the prognostic gene signatures available to date towards a comprehensive genomic fingerprint of the primary tumor. In the future, we should be able to offer individualized treatment to our patients based on a clinical decision-making algorithm that takes into account the clinicopathological parameters, the genomic profile of the primary tumor, the presence of micrometastatic cells and pharmacogenetic data for drug response.

  14. Mammary Fat of Breast Cancer: Gene Expression Profiling and Functional Characterization

    PubMed Central

    Chen, Fei; Fu, Ziyi; Yin, Hong; Lu, Xun; Yu, Jing; Lu, Cheng

    2014-01-01

    Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolated and cultured the stromal vascular cell fraction from mammary fat. The expression of genes related to adipose function (including adipogenesis and secretion) was detected at both the tissue and the cellular level. We also studied mammary fat browning. The results indicated that fat tissue close to malignant and benign lesions exhibited distinctive gene expression profiles and functional characteristics. Although the mammary fat of breast tumors atrophied, it secreted tumor growth stimulatory factors. Browning of mammary fat was observed and browning activity of fat close to malignant breast tumors was greater than that close to benign lesions. Understanding the diversity between these two fat depots may possibly help us improve our understanding of breast cancer pathogenesis and find the key to unlock new anticancer therapies. PMID:25291184

  15. Effects of bleomycin and antioxidants on the fatty acid profile of testicular cancer cell membranes.

    PubMed

    Cort, A; Ozben, T; Melchiorre, M; Chatgilialoglu, C; Ferreri, C; Sansone, A

    2016-02-01

    Bleomycin is used in chemotherapy regimens for the treatment of patients having testicular germ-cell tumor (TGCT). There is no study in the literature investigating the effects of bleomycin on membrane lipid profile in testicular cancer cells. We investigated membrane fatty acid (FA) profiles isolated, derivatized and analyzed by gas chromatography of NTera-2 testicular cancer cells incubated with bleomycin (Bleo) for 24 h in the absence and presence of N-Acetyl-L-Cysteine (NAC) and curcumin (Cur) as commonly used antioxidant adjuvants. At the same time the MAPK pathway and EGFR levels were followed up. Bleomycin treatment increased significantly saturated fatty acids (SFA) of phospholipids at the expense of monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). Bleomycin also led to a significant increase in the trans lipid isomers of oleic and arachidonic acids due to its free radical producing effect. Incubation with bleomycin increased the p38 MAPK and JNK levels and downregulated EGFR pathway. Coincubation of bleomycin with NAC reversed effects caused by bleomycin. Our results highlight the important role of membrane fatty acid remodeling occurring during the use of bleomycin and its concurrent use with antioxidants which can adjuvate the cytotoxic effects of the chemotherapeutic agents.

  16. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses.

    PubMed

    Tang, Zefang; Li, Chenwei; Kang, Boxi; Gao, Ge; Li, Cheng; Zhang, Zemin

    2017-04-12

    Tremendous amount of RNA sequencing data have been produced by large consortium projects such as TCGA and GTEx, creating new opportunities for data mining and deeper understanding of gene functions. While certain existing web servers are valuable and widely used, many expression analysis functions needed by experimental biologists are still not adequately addressed by these tools. We introduce GEPIA (Gene Expression Profiling Interactive Analysis), a web-based tool to deliver fast and customizable functionalities based on TCGA and GTEx data. GEPIA provides key interactive and customizable functions including differential expression analysis, profiling plotting, correlation analysis, patient survival analysis, similar gene detection and dimensionality reduction analysis. The comprehensive expression analyses with simple clicking through GEPIA greatly facilitate data mining in wide research areas, scientific discussion and the therapeutic discovery process. GEPIA fills in the gap between cancer genomics big data and the delivery of integrated information to end users, thus helping unleash the value of the current data resources. GEPIA is available at http://gepia.cancer-pku.cn/.

  17. Multiplexed molecular profiling of prostate cancer specimens using semiconductor quantum dot bioconjugates

    NASA Astrophysics Data System (ADS)

    Xing, Yun; Numora, Takeo; Chung, Leland; Zhau, Haiyen; Nie, Shuming

    2007-02-01

    Quantum dots (QDs) are light emitting semi-conductor nanocrystals with novel optical properties including superior photostability, narrow emission spectra with continuous excitation spectra. These properties make QDs especially suitable for multiplexed fluorescent labeling, live cell imaging, and in vivo animal imaging. The multiplexing potential has been recognized but real applications of biological/clinical significance are few. In this study, we used quantum dots to study epithelial mesenchymal transition (EMT), an important process involved in the bone metastasis of prostate cancer. Two prostate cancer cells lines with distinct molecular profiles, representing the two ends of the EMT process, were selected for this study. Four EMT-related biomarkers including E-cadherin, N-cadherin, Vimentin, and RANKL were stained with QD-antibody conjugates with elongation factor 1alpha as the internal control. Morphological information of the QD-stained cells was obtained by digital-color imaging and quantitative information obtained by spectra analysis using a spectrometer. Two types of analysis were performed: abundance of each biomarker in the same cell line relative to the internal control; and the relative abundance of these markers between the two cell lines. Our results demonstrate the feasibility of QDs for multiplexed profiling of FFPE cells/tissue of clinical significance; however, the standardization and quantification still awaits optimization.

  18. Global Profiling and Molecular Characterization of Alternative Splicing Events Misregulated in Lung Cancer ▿ †

    PubMed Central

    Misquitta-Ali, Christine M.; Cheng, Edith; O'Hanlon, Dave; Liu, Ni; McGlade, C. Jane; Tsao, Ming Sound; Blencowe, Benjamin J.

    2011-01-01

    Alternative splicing (AS) is a widespread mechanism underlying the generation of proteomic and regulatory complexity. However, which of the myriad of human AS events play important roles in disease is largely unknown. To identify frequently occurring AS events in lung cancer, we used AS microarray profiling and reverse transcription-PCR (RT-PCR) assays to survey patient-matched normal and adenocarcinoma tumor tissues from the lungs of 29 individuals diagnosed with non-small cell lung cancer (NSCLC). Of 5,183 profiled alternative exons, four displayed tumor-associated changes in the majority of the patients. These events affected transcripts from the VEGFA, MACF1, APP, and NUMB genes. Similar AS changes were detected in NUMB and APP transcripts in primary breast and colon tumors. Tumor-associated increases in NUMB exon 9 inclusion correlated with reduced levels of NUMB protein expression and activation of the Notch signaling pathway, an event that has been linked to tumorigenesis. Moreover, short hairpin RNA (shRNA) knockdown of NUMB followed by isoform-specific rescue revealed that expression of the exon 9-skipped (nontumor) isoform represses Notch target gene activation whereas expression of the exon 9-included (tumor) isoform lacks this activity and is capable of promoting cell proliferation. The results thus reveal widespread AS changes in NSCLC that impact cell signaling in a manner that likely contributes to tumorigenesis. PMID:21041478

  19. Mammary fat of breast cancer: gene expression profiling and functional characterization.

    PubMed

    Wang, Fengliang; Gao, Sheng; Chen, Fei; Fu, Ziyi; Yin, Hong; Lu, Xun; Yu, Jing; Lu, Cheng

    2014-01-01

    Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolated and cultured the stromal vascular cell fraction from mammary fat. The expression of genes related to adipose function (including adipogenesis and secretion) was detected at both the tissue and the cellular level. We also studied mammary fat browning. The results indicated that fat tissue close to malignant and benign lesions exhibited distinctive gene expression profiles and functional characteristics. Although the mammary fat of breast tumors atrophied, it secreted tumor growth stimulatory factors. Browning of mammary fat was observed and browning activity of fat close to malignant breast tumors was greater than that close to benign lesions. Understanding the diversity between these two fat depots may possibly help us improve our understanding of breast cancer pathogenesis and find the key to unlock new anticancer therapies.

  20. Integrative exploration of genomic profiles for triple negative breast cancer identifies potential drug targets

    PubMed Central

    Wang, Xiaosheng; Guda, Chittibabu

    2016-01-01

    Abstract Background: Triple negative breast cancer (TNBC) is high-risk due to its rapid drug resistance and recurrence, metastasis, and lack of targeted therapy. So far, no molecularly targeted therapeutic agents have been clinically approved for TNBC. It is imperative that we discover new targets for TNBC therapy. Objectives: A large volume of cancer genomics data are emerging and advancing breast cancer research. We may integrate different types of TNBC genomic data to discover molecular targets for TNBC therapy. Data sources: We used publicly available TNBC tumor tissue genomic data in the Cancer Genome Atlas database in this study. Methods: We integratively explored genomic profiles (gene expression, copy number, methylation, microRNA [miRNA], and gene mutation) in TNBC and identified hyperactivated genes that have higher expression, more copy numbers, lower methylation level, or are targets of miRNAs with lower expression in TNBC than in normal samples. We ranked the hyperactivated genes into different levels based on all the genomic evidence and performed functional analyses of the sets of genes identified. More importantly, we proposed potential molecular targets for TNBC therapy based on the hyperactivated genes. Results: Some of the genes we identified such as FGFR2, MAPK13, TP53, SRC family, MUC family, and BCL2 family have been suggested to be potential targets for TNBC treatment. Others such as CSF1R, EPHB3, TRIB1, and LAD1 could be promising new targets for TNBC treatment. By utilizing this integrative analysis of genomic profiles for TNBC, we hypothesized that some of the targeted treatment strategies for TNBC currently in development are more likely to be promising, such as poly (ADP-ribose) polymerase inhibitors, while the others are more likely to be discouraging, such as angiogenesis inhibitors. Limitations: The findings in this study need to be experimentally validated in the future. Conclusion: This is a systematic study that combined 5

  1. Homes away from Home.

    ERIC Educational Resources Information Center

    Hansen, Laurel D.; And Others

    1993-01-01

    Describes the construction of a variety of inexpensive, escape-proof, and safe insect homes--each complete with window, ventilation screen, and cover--so students can observe firsthand the intriguing world of insects. (PR)

  2. Screening for genes and subnetworks associated with pancreatic cancer based on the gene expression profile.

    PubMed

    Long, Jin; Liu, Zhe; Wu, Xingda; Xu, Yuanhong; Ge, Chunlin

    2016-05-01

    The present study aimed to screen for potential genes and subnetworks associated with pancreatic cancer (PC) using the gene expression profile. The expression profile GSE 16515 was downloaded from the Gene Expression Omnibus database, which included 36 PC tissue samples and 16 normal samples. Limma package in R language was used to screen differentially expressed genes (DEGs), which were grouped as up‑ and downregulated genes. Then, PFSNet was applied to perform subnetwork analysis for all the DEGs. Moreover, Gene Ontology (GO) and REACTOME pathway enrichment analysis of up‑ and downregulated genes was performed, followed by protein‑protein interaction (PPI) network construction using Search Tool for the Retrieval of Interacting Genes Search Tool for the Retrieval of Interacting Genes. In total, 1,989 DEGs including 1,461 up‑ and 528 downregulated genes were screened out. Subnetworks including pancreatic cancer in PC tissue samples and intercellular adhesion in normal samples were identified, respectively. A total of 8 significant REACTOME pathways for upregulated DEGs, such as hemostasis and cell cycle, mitotic were identified. Moreover, 4 significant REACTOME pathways for downregulated DEGs, including regulation of β‑cell development and transmembrane transport of small molecules were screened out. Additionally, DEGs with high connectivity degrees, such as CCNA2 (cyclin A2) and PBK (PDZ binding kinase), of the module in the protein‑protein interaction network were mainly enriched with cell‑division cycle. CCNA2 and PBK of the module and their relative pathway cell‑division cycle, and two subnetworks (pancreatic cancer and intercellular adhesion subnetworks) may be pivotal for further understanding of the molecular mechanism of PC.

  3. A Randomized Controlled Trial of Home-Based Exercise for Cancer-Related Fatigue in Women during and after Chemotherapy with or without Radiation Therapy

    PubMed Central

    Dodd, Marylin J.; Cho, Maria H.; Miaskowski, Christine; Painter, Patricia L.; Paul, Steven M.; Cooper, Bruce A.; Duda, John; Krasnoff, Joanne; Bank, Kayee A.

    2010-01-01

    Background Few studies have evaluated an individualized home-based exercise prescription during and after cancer treatment. Objective The purpose was to evaluate the effectiveness of a home-based exercise training intervention, the PRO-SELF FATIGUE CONTROL PROGRAM on the management of cancer related fatigue. Interventions/Methods Participants (N=119) were randomized into one of three groups: Group 1 (EE) received the exercise prescription throughout the study; Group 2 (CE) received their exercise prescription after completing cancer treatment; Group 3 (CC) received usual care. Patients completed the Piper Fatigue Scale, General Sleep Disturbance Scale, Center for Epidemiological Studies-Depression scale, and Worst Pain Intensity Scale. Results All groups reported mild fatigue levels, sleep disturbance and mild pain, but not depression. Using multilevel regression analysis significant linear and quadratic trends were found for change in fatigue and pain (i.e., scores increased, then decreased over time). No group differences were found in the changing scores over time. A significant quadratic effect for the trajectory of sleep disturbance was found, but no group differences were detected over time. No significant time or group effects were found for depression. Conclusions Our home-based exercise intervention had no effect on fatigue or related symptoms associated with cancer treatment. The optimal timing of exercise remains to be determined. Implications for practice Clinicians need to be aware that some physical activity is better than none, and there is no harm in exercise as tolerated during cancer treatment. Further analysis is needed to examine the adherence to exercise. More frequent assessments of fatigue, sleep disturbance, depression, and pain may capture the effect of exercise. PMID:20467301

  4. Prediction of Clinical Outcomes by Chemokine and Cytokine Profiling In CSF from Radiation Treated Breast Cancer Primary with Brain Metastases

    NASA Astrophysics Data System (ADS)

    Lok, Edwin

    Whole brain radiation is the standard treatment for patients with brain metastasis but unfortunately tumors can recover from radiation-induced damage with the help of the immune system. The hypothesis that differences in immunokines in the cerebrospinal fluid (CSF) pre- and post-irradiation could reveal tumor biology and correlate with outcome of patients with metastatic breast cancer to the brain is tested. Collected CSF samples were analyzed using Luminex's multiplexing assays to survey global immunokine levels while Enzyme-Linked Immunosorbent Assays were used to quantify each individual immunokines. Cluster analysis was performed to segregate patients based on their common immunokine profile and each cluster was correlated with survival and other clinical parameters. Breast cancer brain metastasis was found to have altered immunokine profiles in the CSF, and that Interleukin-1α expression was elevated after irradiation. Therefore, immunokine profiling in the CSF could enable cancer physicians to monitor the status of brain metastases.

  5. The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes

    PubMed Central

    Pereira, Bernard; Chin, Suet-Feung; Rueda, Oscar M.; Vollan, Hans-Kristian Moen; Provenzano, Elena; Bardwell, Helen A.; Pugh, Michelle; Jones, Linda; Russell, Roslin; Sammut, Stephen-John; Tsui, Dana W. Y.; Liu, Bin; Dawson, Sarah-Jane; Abraham, Jean; Northen, Helen; Peden, John F.; Mukherjee, Abhik; Turashvili, Gulisa; Green, Andrew R.; McKinney, Steve; Oloumi, Arusha; Shah, Sohrab; Rosenfeld, Nitzan; Murphy, Leigh; Bentley, David R.; Ellis, Ian O.; Purushotham, Arnie; Pinder, Sarah E.; Børresen-Dale, Anne-Lise; Earl, Helena M.; Pharoah, Paul D.; Ross, Mark T.; Aparicio, Samuel; Caldas, Carlos

    2016-01-01

    The genomic landscape of breast cancer is complex, and inter- and intra-tumour heterogeneity are important challenges in treating the disease. In this study, we sequence 173 genes in 2,433 primary breast tumours that have copy number aberration (CNA), gene expression and long-term clinical follow-up data. We identify 40 mutation-driver (Mut-driver) genes, and determine associations between mutations, driver CNA profiles, clinical-pathological parameters and survival. We assess the clonal states of Mut-driver mutations, and estimate levels of intra-tumour heterogeneity using mutant-allele fractions. Associations between PIK3CA mutations and reduced survival are identified in three subgroups of ER-positive cancer (defined by amplification of 17q23, 11q13–14 or 8q24). High levels of intra-tumour heterogeneity are in general associated with a worse outcome, but highly aggressive tumours with 11q13–14 amplification have low levels of intra-tumour heterogeneity. These results emphasize the importance of genome-based stratification of breast cancer, and have important implications for designing therapeutic strategies. PMID:27161491

  6. Extracellular matrix proteins expression profiling in chemoresistant variants of the A2780 ovarian cancer cell line.

    PubMed

    Januchowski, Radosław; Zawierucha, Piotr; Ruciński, Marcin; Nowicki, Michał; Zabel, Maciej

    2014-01-01

    Ovarian cancer is the leading cause of death among gynaecological malignancies. Extracellular matrix (ECM) can affect drug resistance by preventing the penetration of the drug into cancer cells and increased resistance to apoptosis. This study demonstrates alterations in the expression levels of ECM components and related genes in cisplatin-, doxorubicin-, topotecan-, and paclitaxel-resistant variants of the A2780 ovarian cancer cell line. Affymetrix Gene Chip Human Genome Array Strips were used for hybridisations. The genes that had altered expression levels in drug-resistant sublines were selected and filtered by scatter plots. The genes that were up- or downregulated more than fivefold were selected and listed. Among the investigated genes, 28 genes were upregulated, 10 genes were downregulated, and two genes were down- or upregulated depending on the cell line. Between upregulated genes 12 were upregulated very significantly--over 20-fold. These genes included COL1A2, COL12A1, COL21A1, LOX, TGFBI, LAMB1, EFEMP1, GPC3, SDC2, MGP, MMP3, and TIMP3. Four genes were very significantly downregulated: COL11A1, LAMA2, GPC6, and LUM. The expression profiles of investigated genes provide a preliminary insight into the relationship between drug resistance and the expression of ECM components. Identifying correlations between investigated genes and drug resistance will require further analysis.

  7. Tissue metabolic profiling of lymph node metastasis of colorectal cancer assessed by 1H NMR.

    PubMed

    Zhang, Hailong; Qiao, Liang; Li, Xiaopeng; Wan, Yang; Yang, Li; Wang, Huijuan

    2016-12-01

    Lymph node metastasis is a decisive prognostic and therapeutic staging factor for colorectal cancer (CRC), which is one of the most prevalent types of cancer and a malignant tumor. The metabolic profiling of tissue samples from a large cohort of lymph node non‑metastatic CRC patients (n=73), lymph node metastatic CRC patients (n=52) and normal controls (n=41) was performed using 1H nuclear magnetic resonance (NMR) together with multivariate statistical analyses. Excellent separation was obtained between CRC patients and normal controls, and CRC patients were also perfectly classified according to lymph node metastasis. Forty‑two distinguishing metabolites were identified, which revealed disturbance of glycolysis, glutaminolysis, fatty acid metabolism, choline metabolism and amino acids, suggesting that cellular functions in energy production, macromolecular synthesis, oxidative stress and immune escape of cancer cells are affected in CRC. In total, 10 tissue metabolites were significantly disturbed between non‑metastatic and metastatic CRC patients. The present study firstly staged CRC patients by lymph node metastasis by metabolomic approach. The identified metabolites may be associated with the neoplasia, invasion and metastasis of the tumor. The results suggest the promising application of these metabolites in clinical therapy, and further understanding of the related mechanism warrants further investigation.

  8. Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers.

    PubMed

    Borad, Mitesh J; Egan, Jan B; Condjella, Rachel M; Liang, Winnie S; Fonseca, Rafael; Ritacca, Nicole R; McCullough, Ann E; Barrett, Michael T; Hunt, Katherine S; Champion, Mia D; Patel, Maitray D; Young, Scott W; Silva, Alvin C; Ho, Thai H; Halfdanarson, Thorvardur R; McWilliams, Robert R; Lazaridis, Konstantinos N; Ramanathan, Ramesh K; Baker, Angela; Aldrich, Jessica; Kurdoglu, Ahmet; Izatt, Tyler; Christoforides, Alexis; Cherni, Irene; Nasser, Sara; Reiman, Rebecca; Cuyugan, Lori; McDonald, Jacquelyn; Adkins, Jonathan; Mastrian, Stephen D; Valdez, Riccardo; Jaroszewski, Dawn E; Von Hoff, Daniel D; Craig, David W; Stewart, A Keith; Carpten, John D; Bryce, Alan H

    2016-12-01

    DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single assay to provide: therapeutic target prioritisation, novel target discovery/application and comprehensive germline assessment. A prospective study in 35 advanced/refractory cancer patients was conducted using CLIA-compliant IGP. Feasibility was assessed by estimating time to results (TTR), prioritising/assigning putative therapeutic targets, assessing drug access, ascertaining germline alterations, and assessing patient preferences/perspectives on data use/reporting. Therapeutic targets were identified using biointelligence/pathway analyses and interpreted by a Genomic Tumour Board. Seventy-five percent of cases harboured 1-3 therapeutically targetable mutations/case (median 79 mutations of potential functional significance/case). Median time to CLIA-validated results was 116 days with CLIA-validation of targets achieved in 21/22 patients. IGP directed treatment was instituted in 13 patients utilising on/off label FDA approved drugs (n = 9), clinical trials (n = 3) and single patient IND (n = 1). Preliminary clinical efficacy was noted in five patients (two partial response, three stable disease). Although barriers to broader application exist, including the need for wider availability of therapies, IGP in a CLIA-framework is feasible and valuable in selection/prioritisation of anti-cancer therapeutic targets.

  9. Comprehensive genomic sequencing and the molecular profiles of clinically advanced breast cancer.

    PubMed

    Ross, Jeffrey S; Gay, Laurie M

    2017-02-01

    Targeting specific mutations that have arisen within a tumour is a promising means of increasing the efficacy of treatments, and breast cancer is no exception to this new paradigm of personalised medicine. Traditional DNA sequencing methods used to characterise clinical cancer specimens and impact treatment decisions are highly sensitive, but are often limited in their scope to known mutational hot spots. Next-generation sequencing (NGS) technologies can also test for these well-known hot spots, as well as identifying insertions and deletions, copy number changes such as ERBB2 (HER2) gene amplification, and a wide array of fusion or rearrangement events. By rapidly analysing many genes in parallel, NGS technologies can make efficient use of precious biopsy material. Comprehensive genomic profiling (CGP) by NGS can reveal targetable, clinically relevant genomic alterations that can stratify tumours by predicted sensitivity to a variety of therapies, including HER2- or MTOR-targeted therapies, immunotherapies, and other kinase inhibitors. Many clinically relevant genomic alterations would not be identified by IHC or hotspot testing, but can be detected by NGS. In addition to the most common breast carcinoma subtypes, rare subtypes analysed with CGP also harbour clinically relevant genomic alterations that can potentially direct therapy selection, illustrating that CGP is a powerful tool for guiding treatment across all breast cancer subtypes.

  10. Global gene expression profiles induced by phytoestrogens in human breast cancer cells.

    PubMed

    Dip, Ramiro; Lenz, Sarah; Antignac, Jean-Philippe; Le Bizec, Bruno; Gmuender, Hans; Naegeli, Hanspeter

    2008-03-01

    The nutritional intake of phytoestrogens seems to reduce the risk of breast cancer or other neoplastic diseases. However, these epidemiological findings remain controversial because low doses of phytoestrogens, achievable through soy-rich diets, stimulate the proliferation of estrogen-sensitive tumor cells. The question of whether such phytochemicals prevent cancer or rather pose additional health hazards prompted us to examine global gene expression programs induced by a typical soy product. After extraction from soymilk, phytoestrogens were deconjugated and processed through reverse- and normal-phase cartridges. The resulting mixture was used to treat human target cells that represent a common model system for mammary tumorigenesis. Analysis of mRNA on high-density microarrays revealed that soy phytoestrogens induce a genomic fingerprint that is indistinguishable from the transcriptional effects of the endogenous hormone 17beta-estradiol. Highly congruent responses were also observed by comparing the physiologic estradiol with daidzein, coumestrol, enterolactone, or resveratrol, each representing distinct phytoestrogen structures. More diverging transcriptional profiles were generated when an inducible promoter was used to reconstitute the expression of estrogen receptor beta (ERbeta). Therefore, phytoestrogens appear to mitigate estrogenic signaling in the presence of both ER subtypes but, in late-stage cancer cells lacking ERbeta, these phytochemicals contribute to a tumor-promoting transcriptional signature.

  11. LncRNAs expression profiling in normal ovary, benign ovarian cyst and malignant epithelial ovarian cancer

    PubMed Central

    Wang, Huan; Fu, Ziyi; Dai, Chencheng; Cao, Jian; Liu, Xiaoguang; Xu, Juan; Lv, Mingming; Gu, Yun; Zhang, Jingmin; Hua, Xiangdong; Jia, Genmei; Xu, Sujuan; Jia, Xuemei; Xu, Pengfei

    2016-01-01

    Long noncoding RNA (lncRNA) has been recognized as a regulator of gene expression, and the dysregulation of lncRNAs is involved in the progression of many types of cancer, including epithelial ovarian cancer (EOC). To explore the potential roles of lncRNAs in EOC, we performed lncRNA and mRNA microarray profiling in malignant EOC, benign ovarian cyst and healthy control tissues. In this study, 663 transcripts of lncRNAs were found to be differentially expressed in malignant EOC compared with benign and normal control tissues. We also selected 18 altered lncRNAs to confirm the validity of the microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, especially the cell cycle. Furthermore, Series Test of Cluster (STC) and lncRNA-mRNA co-expression network analyses were conducted to predict lncRNA expression trends and the potential target genes of lncRNAs. We also determined that two antisense lncRNAs (RP11-597D13.9 and ADAMTS9-AS1) were associated with their nearby coding genes (FAM198B, ADAMTS9), which participated in cancer progression. This study offers helpful information to understand the initiation and development mechanisms of EOC. PMID:27941916

  12. 6 Common Cancers - Lung Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents For ... Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the next ...

  13. 6 Common Cancers - Skin Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Skin Cancer Past Issues / Spring 2007 Table of Contents For ... AP Photo/Herald-Mail, Kevin G. Gilbert Skin Cancer Skin cancer is the most common form of ...

  14. Niche-Dependent Gene Expression Profile of Intratumoral Heterogeneous Ovarian Cancer Stem Cell Populations

    PubMed Central

    Abelson, Sagi; Shamai, Yeela; Berger, Liron; Skorecki, Karl; Tzukerman, Maty

    2013-01-01

    Intratumoral heterogeneity challenges existing paradigms for anti-cancer therapy. We have previously demonstrated that the human embryonic stem cells (hESC)-derived cellular microenvironment in immunocompromised mice, enables functional distinction of heterogeneous tumor cells, including cells which do not grow into a tumor in a conventional direct tumor xenograft platform. We have identified and characterized six cancer cell subpopulations each clonally expanded from a single cell, derived from human ovarian clear cell carcinoma of a single tumor, to demonstrate striking intratumoral phenotypic heterogeneity that is dynamically dependent on the tumor growth microenvironment. These cancer cell subpopulations, characterized as cancer stem cell subpopulations, faithfully recapitulate the full spectrum of histological phenotypic heterogeneity known for human ovarian clear cell carcinoma. Each of the six subpopulations displays a different level of morphologic and tumorigenic differentiation wherein growth in the hESC-derived microenvironment favors growth of CD44+/aldehyde dehydrogenase positive pockets of self-renewing cells that sustain tumor growth through a process of tumorigenic differentiation into CD44-/aldehyde dehydrogenase negative derivatives. Strikingly, these derivative cells display microenvironment-dependent plasticity with the capacity to restore self-renewal markers and CD44 expression. In the current study, we delineate the distinct gene expression and epigenetic profiles of two such subpopulations, representing extremes of phenotypic heterogeneity in terms of niche-dependent self-renewal and tumorigenic differentiation. By combining Gene Set Enrichment, Gene Ontology and Pathway-focused array analyses with methylation status, we propose a suite of robust differences in tumor self-renewal and differentiation pathways that underlie the striking intratumoral phenotypic heterogeneity which characterize this and other solid tumor malignancies. PMID

  15. miRNA profiling of circulating EpCAM+ extracellular vesicles: promising biomarkers of colorectal cancer

    PubMed Central

    Ostenfeld, Marie Stampe; Jensen, Steffen Grann; Jeppesen, Dennis Kjølhede; Christensen, Lise-Lotte; Thorsen, Stine Buch; Stenvang, Jan; Hvam, Michael Lykke; Thomsen, Anni; Mouritzen, Peter; Rasmussen, Mads Heilskov; Nielsen, Hans Jørgen; Ørntoft, Torben Falck; Andersen, Claus Lindbjerg

    2016-01-01

    Cancer cells secrete small membranous extracellular vesicles (EVs) into their microenvironment and circulation. These contain biomolecules, including proteins and microRNAs (miRNAs). Both circulating EVs and miRNAs have received much attention as biomarker candidates for non-invasive diagnostics. Here we describe a sensitive analytical method for isolation and subsequent miRNA profiling of epithelial-derived EVs from blood samples of patients with colorectal cancer (CRC). The epithelial-derived EVs were isolated by immunoaffinity-capture using the epithelial cell adhesion molecule (EpCAM) as marker. This approach mitigates some of the specificity issues observed in earlier studies of circulating miRNAs, in particular the negative influence of miRNAs released by erythrocytes, platelets and non-epithelial cells. By applying this method to 2 small-scale patient cohorts, we showed that blood plasma isolated from CRC patients prior to surgery contained elevated levels of 13 EpCAM+-EV miRNAs compared with healthy individuals. Upon surgical tumour removal, the plasma levels of 8 of these were reduced (miR-16-5p, miR-23a-3p, miR-23b-3p, miR-27a-3p, miR-27b-3p, miR-30b-5p, miR-30c-5p and miR-222-3p). These findings indicate that the miRNAs are of tumour origin and may have potential as non-invasive biomarkers for detection of CRC. This work describes a non-invasive blood-based method for sensitive detection of cancer with potential for clinical use in relation to diagnosis and screening. We used the method to study CRC; however, it is not restricted to this disease. It may in principle be used to study any cancer that release epithelial-derived EVs into circulation. PMID:27576678

  16. Proteome and Transcriptome Profiles of a Her2/Neu-driven Mouse Model of Breast Cancer

    SciTech Connect

    Schoenherr, Regine M.; Kelly-Spratt, Karen S.; Lin, Chen Wei; Whiteaker, Jeffrey R.; Liu, Tao; Holzman, Ted; Coleman, Ilsa; Feng, Li-Chia; Lorentzen, Travis D.; Krasnoselsky, Alexei L.; Wang, Pei; Liu, Yan; Gurley, Kay E.; Amon, Lynn M.; Schepmoes, Athena A.; Moore, Ronald J.; Camp, David G.; Chodosh, Lewis A.; Smith, Richard D.; Nelson, Peter S.; McIntosh, Martin; Kemp, Christopher; Paulovich, Amanda G.

    2011-04-01

    In recent years, mouse models have proven to be invaluable in expanding our understanding of cancer biology. We have amassed a tremendous amount of proteomics and transcriptomics data profiling blood and tissues from a Her2-driven mouse model of breast cancer that closely recapitulates the pathology and natural history of human breast cancer. The purpose of this report is to make all of these data publicly available in raw and processed forms, as a resource to the community. Importantly, high quality biospecimens from this same mouse model are freely available through a sample repository that we established, so researchers can readily obtain samples to test biological hypotheses without the need of breeding animals and collecting biospecimens. Specifically, six proteomics and six transcriptomics datasets are available, with the former encompassing 841 liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments of both plasma and tissue samples, and the latter including 255 individual microarray analyses of five different tissue types (thymus, spleen, liver, blood cells, and breast ± laser capture microdissection). A total of 18,880 unique peptides were identified with a PeptideProphet error rate ≤1%, with 3884 non-redundant protein groups identified in five plasma datasets, and 1659 non-redundant protein groups in a tissue dataset (4977 non-redundant protein groups in total). We anticipate that these data will be of use to the community for software tool development, investigations of analytical variation in MS/MS data, development of quality control tools (multiple technical replicates are provided for a subset of the data), empirical selection of proteotypic peptides for multiple reaction monitoring mass spectrometry, and for advancing our understanding of cancer biology.

  17. Home Schooling Children with Special Needs.

    ERIC Educational Resources Information Center

    Duffey, Jane G.

    2002-01-01

    A survey of 121 families who were home schooling children with special needs found family profiles were similar to the general home schooling population and, unlike the general home schooling population, children often spent as much time in a school setting as in a home school environment. Four case studies identified themes as needs-based…

  18. Nursing Homes

    MedlinePlus

    ... our e-newsletter! Aging & Health A to Z Nursing Homes Basic Facts & Information Nursing homes have changed ... physical health and/or mental disabilities. Is a Nursing Home Right for You? Almost half of all ...

  19. Home Modifications

    MedlinePlus

    ... My Home HomeFit ? (AARP) (PDF) Back to top Financial Assistance Minor improvements and repairs can cost between $ ... Learn more by visiting https://www.ncoa.org/economic-security/home-equity/ . Search for additional resources in ...

  20. Cancer du sein au Maroc: profil phénotypique des tumeurs

    PubMed Central

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

    2016-01-01

    Le cancer du sein est le plus fréquent chez la femme et figure parmi les principales causes de mortalité liées au cancer. La curabilité de ce type tumoral est en augmentation, grâce aux programmes de dépistage et aux progrès thérapeutiques, qui ont certes augmenté la survie des patients. Mais des défis restent à relever en rapport avec l’instabilité phénotypique des cellules cancéreuses. L’objectif de ce travail est d’étudier le profil phénotypique du cancer du sein chez les patients pris en charge au Centre Mohammed VI pour le traitement des Cancers, durant les années 2013-2014. Il s’agit d’une étude transversale sur deux années, incluant les cas du cancer du sein pris en charge au Centre. Le recueil des données était fait à partir des dossiers des patients et analysés par le logiciel Epi Info. 1277 patients ont été pris en charge au sein de notre centre. 99,5% des cas de sexe féminin, l’âge moyen était 50,20 ± 11,34 ans. Le type histologique le plus fréquent était le carcinome canalaire infiltrant (80,7% des cas). Le stade diagnostic était précoce (56,9%). Le phénotype moléculaire le plus fréquent était le luminal A (41,4% des cas). Le luminal B, le HER2 et les triples négatifs étaient dans respectivement 10,4%, 6,3%, 11,2% des cas. L’étude du phénotype tumoral des patients atteints du cancer du sein permet l’orientation du clinicien dans le choix du traitement, et des décideurs dans la planification de programmes de lutte contre cette pathologie. PMID:28292037

  1. Integrated analysis of genome-wide DNA methylation and gene expression profiles identifies potential novel biomarkers of rectal cancer

    PubMed Central

    Zhang, Jinning; Zhou, Yuhui; Dang, Shuwei; Chen, Hongsheng; Wu, Qiong; Liu, Ming

    2016-01-01

    DNA methylation was regarded as the promising biomarker for rectal cancer diagnosis. However, the optimal methylation biomarkers with ideal diagnostic performance for rectal cancer are still limited. To identify new molecular markers for rectal cancer, we mapped DNA methylation and transcriptomic profiles in the six rectal cancer and paired normal samples. Further analysis revealed the hypermethylated probes in cancer prone to be located in gene promoter. Meanwhile, transcriptome analysis presented 773 low-expressed and 1,161 over-expressed genes in rectal cancer. Correction analysis identified a panel of 36 genes with an inverse correlation between methylation and gene expression levels, including 10 known colorectal cancer related genes. From the other 26 novel marker genes, GFRA1 and GSTM2 were selected for further analysis on the basis of their biological functions. Further experiment analysis confirmed their methylation and expression status in a larger number (44) of rectal cancer samples, and ROC curves showed higher AUC than SEPT9, which has been used as a biomarker in rectal cancer. Our data suggests that aberrant DNA methylation of contiguous CpG sites in methylation array may be potential diagnostic markers of rectal cancer. PMID:27566576

  2. Using oxygen at home

    MedlinePlus

    Oxygen - home use; COPD - home oxygen; Chronic obstructive airways disease - home oxygen; Chronic obstructive lung disease - home oxygen; Chronic bronchitis - home oxygen; Emphysema - home oxygen; Chronic respiratory ...

  3. Biliary tract cancers: molecular profiling as a tool for treatment decisions. A literature review.

    PubMed

    Berardi, Rossana; Rossana, Berardi; Scartozzi, Mario; Mario, Scartozzi; Freddari, Federica; Federica, Freddari; Squadroni, Michela; Michela, Squadroni; Santinelli, Alfredo; Alfredo, Santinelli; Bearzi, Italo; Italo, Bearzi; Fabris, Guidalberto; Guidalberto, Fabris; Cascinu, Stefano; Stefano, Cascinu

    2006-08-01

    Biliary tract cancer is a quite rare disease; despite recent significant advances in imaging modalities, most of the patients have advanced disease at presentation thus making radical surgery not feasible. Many different chemotherapeutic regimens have been investigated in small uncontrolled studies, with generally disappointing results. We extensively reviewed the literature on this topic trying to give an explanation to chemoresistance in this setting of patients and considering the molecular profiling as a tool for treatment decision. This review is divided in two parts, in the first one we illustrated chemotherapy results and possible mechanisms of resistance. In the second part we analysed the new molecular targets developing an hypothesis about the future therapeutics perspectives.

  4. Molecular profiling of indolent human prostate cancer: tackling technical challenges to achieve high-fidelity genome-wide data.

    PubMed

    Dunn, Thomas A; Fedor, Helen L; De Marzo, Angelo M; Luo, Jun

    2012-05-01

    The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men, and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases. Since progressive acquisition and accumulation of genomic alterations, both genetic and epigenetic, is a defining feature of all human cancers at different stages of disease progression, it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer. Approaches capable of detecting such alterations on a genome-wide level are the most promising. Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression, and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment. However, defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge, particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded (FFPE) tissue specimens. Here, we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies, identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues, and highlight recent progresses in efforts to address these technical challenges.

  5. Prediction of Response to Preoperative Chemoradiotherapy in Rectal Cancer by Multiplex Kinase Activity Profiling

    SciTech Connect

    Folkvord, Sigurd; Flatmark, Kjersti; Dueland, Svein

    2010-10-01

    Purpose: Tumor response of rectal cancer to preoperative chemoradiotherapy (CRT) varies considerably. In experimental tumor models and clinical radiotherapy, activity of particular subsets of kinase signaling pathways seems to predict radiation response. This study aimed to determine whether tumor kinase activity profiles might predict tumor response to preoperative CRT in locally advanced rectal cancer (LARC). Methods and Materials: Sixty-seven LARC patients were treated with a CRT regimen consisting of radiotherapy, fluorouracil, and, where possible, oxaliplatin. Pretreatment tumor biopsy specimens were analyzed using microarrays with kinase substrates, and the resulting substrate phosphorylation patterns were correlated with tumor response to preoperative treatment as assessed by histomorphologic tumor regression grade (TRG). A predictive model for TRG scores from phosphosubstrate signatures was obtained by partial-least-squares discriminant analysis. Prediction performance was evaluated by leave-one-out cross-validation and use of an independent test set. Results: In the patient population, 73% and 15% were scored as good responders (TRG 1-2) or intermediate responders (TRG 3), whereas 12% were assessed as poor responders (TRG 4-5). In a subset of 7 poor responders and 12 good responders, treatment outcome was correctly predicted for 95%. Application of the prediction model on the remaining patient samples resulted in correct prediction for 85%. Phosphosubstrate signatures generated by poor-responding tumors indicated high kinase activity, which was inhibited by the kinase inhibitor sunitinib, and several discriminating phosphosubstrates represented proteins derived from signaling pathways implicated in radioresistance. Conclusions: Multiplex kinase activity profiling may identify functional biomarkers predictive of tumor response to preoperative CRT in LARC.

  6. Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis

    PubMed Central

    Emmanuel, Catherine; Gava, Natalie; Kennedy, Catherine; Balleine, Rosemary L.; Sharma, Raghwa; Wain, Gerard; Brand, Alison; Hogg, Russell; Etemadmoghadam, Dariush; George, Joshy; Birrer, Michael J.; Clarke, Christine L.; Chenevix-Trench, Georgia; Bowtell, David D. L.; Harnett, Paul R.; deFazio, Anna

    2011-01-01

    Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute

  7. A survey of immunohistochemical biomarkers for basal-like breast cancer against a gene expression profile gold standard.

    PubMed

    Won, Jennifer R; Gao, Dongxia; Chow, Christine; Cheng, Jinjin; Lau, Sherman Y H; Ellis, Matthew J; Perou, Charles M; Bernard, Philip S; Nielsen, Torsten O

    2013-11-01

    Gene expression profiling of breast cancer delineates a particularly aggressive subtype referred to as 'basal-like', which comprises ∼15% of all breast cancers, afflicts younger women and is refractory to endocrine and anti-HER2 therapies. Immunohistochemical surrogate definitions for basal-like breast cancer, such as the clinical ER/PR/HER2 triple-negative phenotype and models incorporating positive expression for CK5 (CK5/6) and/or EGFR are heavily cited. However, many additional biomarkers for basal-like breast cancer have been described in the literature. A parallel comparison of 46 proposed immunohistochemical biomarkers of basal-like breast cancer was performed against a gene expression profile gold standard on a tissue microarray containing 42 basal-like and 80 non-basal-like breast cancer cases. Ki67 and PPH3 were the most sensitive biomarkers (both 92%) positively expressed in the basal-like subtype, whereas CK14, IMP3 and NGFR were the most specific (100%). Among biomarkers surveyed, loss of INPP4B (a negative regulator of phosphatidylinositol signaling) was 61% sensitive and 99% specific with the highest odds ratio (OR) at 108, indicating the strongest association with basal-like breast cancer. Expression of nestin, a common marker of neural progenitor cells that is also associated with the triple-negative/basal-like phenotype and poor breast cancer prognosis, possessed the second highest OR at 29 among the 46 biomarkers surveyed, as well as 54% sensitivity and 96% specificity. As a positively expressed biomarker, nestin possesses technical advantages over INPP4B that make it a more ideal biomarker for identification of basal-like breast cancer. The comprehensive immunohistochemical biomarker survey presented in this study is a necessary step for determining an optimized surrogate immunopanel that best defines basal-like breast cancer in a practical and clinically accessible way.

  8. MicroRNA expression profiles of drug-resistance breast cancer cells and their exosomes

    PubMed Central

    Zhong, Shanliang; Chen, Xiu; Wang, Dandan; Zhang, Xiaohui; Shen, Hongyu; Yang, Sujin; Lv, Mengmeng; Tang, Jinhai; Zhao, Jianhua

    2016-01-01

    Exosomes have been shown to transmit drug resistance through delivering miRNAs. We aimed to explore their roles in breast cancer. Three resistant sublines were established by exposing parental MDA-MB-231 cell line to docetaxel, epirubicin and vinorelbine, respectively. Preneoadjuvant chemotherapy biopsies and paired surgically-resected specimens embedded in paraffin from 23 breast cancer patients were collected. MiRNA expression profiles of the cell lines and their exosomes were evaluated using microarray. The result showed that most miRNAs in exosomes had a lower expression level than that in cells, however, some miRNAs expressed higher in exosomes than in cells, suggesting a number of miRNAs is concentrated in exosomes. Among the dysregulated miRNAs, 22 miRNAs were consistently up-regulated in exosomes and their cells of origin. We further found that 12 of the 22 miRNAs were significantly up-regulated after preneoadjuvant chemotherapy. Further study of the role of these 12 miRNAs in acquisition of drug resistance is needed to clarify their contribution to chemoresistance. PMID:26910922

  9. BH3 profiling and a toolkit of BH3-mimetic drugs predict anti-apoptotic dependence of cancer cells

    PubMed Central

    Butterworth, Michael; Pettitt, Andrew; Varadarajan, Shankar; Cohen, Gerald M

    2016-01-01

    Background: Anti-apoptotic BCL-2 family members antagonise apoptosis by sequestering their pro-apoptotic counterparts. The balance between the different BCL-2 family members forms the basis of BH3 profiling, a peptide-based technique used to predict chemosensitivity of cancer cells. Recent identification of cell-permeable, selective inhibitors of BCL-2, BCL-XL and MCL-1, further facilitates the determination of the BCL-2 family dependency of cancer cells. Methods: We use BH3 profiling in combination with cell death analyses using a chemical inhibitor toolkit to assess chemosensitivity of cancer cells. Results: Both BH3 profiling and the inhibitor toolkit effectively predict chemosensitivity of cells addicted to a single anti-apoptotic protein but a combination of both techniques is more instructive when cell survival depends on more than one anti-apoptotic protein. Conclusions: The inhibitor toolkit provides a rapid, inexpensive and simple means to assess the chemosensitivity of tumour cells and in conjunction with BH3 profiling offers much potential in personalising cancer therapy. PMID:26954718

  10. Expression profile of circulating microRNAs as a promising fingerprint for cervical cancer diagnosis and monitoring

    PubMed Central

    JIA, WENHUI; WU, YUANZHE; ZHANG, QIN; GAO, GE; ZHANG, CHENYU; XIANG, YANG

    2015-01-01

    Sensitive and specific biomarkers for the early detection of cervical cancer are urgently required to reduce the high morbidity and mortality of this disease. We previously demonstrated that circulating microRNAs (miRNAs) are correlated with certain types of human cancer. The aim of this study was to investigate the altered profile of serum miRNAs in cervical cancer patients in order to predict cervical cancer at a relative early stage. Serum samples were collected from 213 cervical cancer patients and 158 age- and ethnicity-matched controls. An initial screening of miRNA expression was performed by Solexa sequencing. Differential expression was validated using the stem-loop miRNA quantitative polymerase chain reaction (qPCR) assay in individual samples and the samples were arranged by two-phase selection and validation. The Solexa sequencing results revealed 12 markedly upregulated serum miRNAs in cervical cancer patients compared with controls. The reverse transcription-qPCR analysis identified a profile of 5 serum miRNAs (miR-21, −29a, −25, −200a and −486-5p) as a cervical cancer biomarker. The receiver operating characteristic curves indicated that a panel of 5 miRNAs constitutes a more sensitive and specific diagnostic test compared with any single miRNA-based assay, the squamous cell carcinoma antigen or the carbohydrate antigen 125. More importantly, miR-29a and miR-200a may indicate tumor histological grade and progression stage. Therefore, a 5-miRNA signature identified from genome-wide serum miRNA expression profiling may serve as a fingerprint for cervical cancer diagnosis. PMID:26171195

  11. Identification of plasma protein profiles associated with risk groups of prostate cancer patients

    PubMed Central

    Nordström, Malin; Wingren, Christer; Rose, Carsten; Bjartell, Anders; Becker, Charlotte; Lilja, Hans; Borrebaeck, Carl AK

    2015-01-01

    Purpose Early detection of prostate cancer (PC) using prostate-specific antigen (PSA) in blood reduces PC-death among unscreened men. However, due to modest specificity of PSA at commonly used cut-offs, there are urgent needs for additional biomarkers contributing enhanced risk classification among men with modestly elevated PSA. Experimental design Recombinant antibody microarrays were applied for protein expression profiling of 80 plasma samples from routine PSA-measurements, a priori divided into four risk groups, based on levels of total and %free PSA. Results The results demonstrated that plasma protein profiles could be identified that pinpointed PC (a malignant biomarker signature) and most importantly that showed moderate to high correlation with biochemically defined PC risk groups. Notably, the data also implied that the risk group with mid-range PSA and low %free PSA, a priori known to be heterogeneous, could be further stratified into two subgroups, more resembling the lowest and highest risk groups, respectively. Conclusions and clinical relevance In this pilot study, we have shown that plasma protein biomarker signatures, associated with risk groups of PC, could be identified from crude plasma samples using affinity proteomics. This approach could in the longer perspective provide novel opportunities for improved risk classification of PC patients. PMID:25196118

  12. Gene expression profiles of circulating tumor cells versus primary tumors in metastatic breast cancer.

    PubMed

    Onstenk, Wendy; Sieuwerts, Anieta M; Weekhout, Marleen; Mostert, Bianca; Reijm, Esther A; van Deurzen, Carolien H M; Bolt-de Vries, Joan B; Peeters, Dieter J; Hamberg, Paul; Seynaeve, Caroline; Jager, Agnes; de Jongh, Felix E; Smid, Marcel; Dirix, Luc Y; Kehrer, Diederik F S; van Galen, Anne; Ramirez-Moreno, Raquel; Kraan, Jaco; Van, Mai; Gratama, Jan W; Martens, John W M; Foekens, John A; Sleijfer, Stefan

    2015-06-28

    Before using circulating tumor cells (CTCs) as liquid biopsy, insight into molecular discrepancies between CTCs and primary tumors is essential. We characterized CellSearch-enriched CTCs from 62 metastatic breast cancer (MBC) patients with ≥5 CTCs starting first-line systemic treatment. Expression levels of 35 tumor-associated, CTC-specific genes, including ESR1, coding for the estrogen receptor (ER), were measured by reverse transcription quantitative polymerase chain reaction and correlated to corresponding primary tumors. In 30 patients (48%), gene expression profiles of 35 genes were discrepant between CTCs and the primary tumor, but this had no prognostic consequences. In 15 patients (24%), the expression of ER was discrepant. Patients with ER-negative primary tumors and ER-positive CTCs had a longer median TTS compared to those with concordantly ER-negative CTCs (8.5 versus 2.1 months, P = 0.05). From seven patients, an axillary lymph node metastasis was available. In two patients, the CTC profiles better resembled the lymph node metastasis than the primary tumor. Our findings suggest that molecular discordances between CTCs and primary tumors frequently occur, but that this bears no prognostic consequences. Alterations in ER-status between primary tumors and CTCs might have prognostic implications.

  13. Genetic profiling and epidermal growth factor receptor-directed therapy in nonsmall cell lung cancer.

    PubMed

    Cadranel, J; Zalcman, G; Sequist, L

    2011-01-01

    The principle of preferentially selecting patients most likely to benefit from therapy according to their genetic profile has led to substantial clinical benefit in some tumour types, and has potential to considerably refine treatment in advanced nonsmall cell lung cancer (NSCLC). Effective, reliable use of molecular biomarkers to inform clinical practice requires the standardisation of testing methods and careful assessment of biomarkers' predictive and prognostic value. Although a number of studies have shown that patients with activating mutations in exons 18-21 of the epidermal growth factor receptor (EGFR) gene respond particularly well to gefitinib and erlotinib, a prospective, randomised study was needed to differentiate between the prognostic and predictive value of EGFR mutations. From one such study, it appeared that mutational testing should become standard at diagnosis, at least for adenocarcinoma patients with a never or low smoking history, as clinical predictors are insufficient to optimise treatment. However, outstanding questions remain: what are the treatment options for patients with tumours resistant to erlotinib/gefitinib? What conclusions about treatment can we draw from EGFR copy number or KRAS mutation status? What role should anti-EGFR antibodies play in NSCLC treatment, and in which patients? This review considers current evidence linking biomarker profile to efficacy of EGFR-targeted therapy in NSCLC, and clinical implications of recent findings.

  14. Unique DNA methylome profiles in CpG island methylator phenotype colon cancers

    PubMed Central

    Xu, Yaomin; Hu, Bo; Choi, Ae-Jin; Gopalan, Banu; Lee, Byron H.; Kalady, Matthew F.; Church, James M.; Ting, Angela H.

    2012-01-01

    A subset of colorectal cancers was postulated to have the CpG island methylator phenotype (CIMP), a higher propensity for CpG island DNA methylation. The validity of CIMP, its molecular basis, and its prognostic value remain highly controversial. Using MBD-isolated genome sequencing, we mapped and compared genome-wide DNA methylation profiles of normal, non-CIMP, and CIMP colon specimens. Multidimensional scaling analysis revealed that each specimen could be clearly classified as normal, non-CIMP, and CIMP, thus signifying that these three groups have distinctly different global methylation patterns. We discovered 3780 sites in various genomic contexts that were hypermethylated in both non-CIMP and CIMP colon cancers when compared with normal colon. An additional 2026 sites were found to be hypermethylated in CIMP tumors only; and importantly, 80% of these sites were located in CpG islands. These data demonstrate on a genome-wide level that the additional hypermethylation seen in CIMP tumors occurs almost exclusively at CpG islands and support definitively that these tumors were appropriately named. When these sites were examined more closely, we found that 25% were adjacent to sites that were also hypermethylated in non-CIMP tumors. Thus, CIMP is also characterized by more extensive methylation of sites that are already prone to be hypermethylated in colon cancer. These observations indicate that CIMP tumors have specific defects in controlling both DNA methylation seeding and spreading and serve as an important first step in delineating molecular mechanisms that control these processes. PMID:21990380

  15. Gene expression profiling identifies Fibronectin 1 and CXCL9 as candidate biomarkers for breast cancer screening

    PubMed Central

    Ruiz-Garcia, E; Scott, V; Machavoine, C; Bidart, J M; Lacroix, L; Delaloge, S; Andre, F

    2010-01-01

    Background: There is a need to develop blood-based bioassays for breast cancer (BC) screening. In this study, differential gene expression between BC samples and benign tumours was used to identify candidate biomarkers for blood-based screening. Methods: We identified two proteins (Fibronectin 1 and CXCL9) from a gene expression data set that included 120 BC samples and 45 benign lesions. These proteins fulfil the following criteria: differential gene expression between cancer and benign lesion, protein released in the extracellular medium and stable in the serum, commercially available ELISA kit, ELISA accuracy in a feasibility study. Protein concentrations were determined by ELISA. Blood samples were from normal volunteers (n=119) and early BC patients (n=133). Results: Seventy-three per cent of patients had cT1-T2 tumour. Patients had higher CXCL9 and Fibronectin 1 concentrations than volunteers. CXCL9 mean concentration was 851 and 635 pg ml−1 for patients and volunteers respectively (P=0.013). CXCL9 concentration was significantly higher in patients with estrogen receptor (ER)-negative compared with volunteers (P=0.003), data consistent with gene expression profile. Fibronectin 1 mean concentration was 190 μg ml−1 for patients and 125 μg ml−1 for volunteers (P<0.001). Areas under the curve for BC diagnosis were 0.78 and 0.62 for Fibronectin 1 and CXCL9 respectively. A combined score including Fibronectin 1 and CXCL9 dosages presented 53% of sensitivity and 98% of specificity. Similar performances were observed for ER-negative tumours. Conclusions: This study suggests that Fibronectin 1/CXCL9 dosage in serum could screen a significant rate of BC, including ER-negative, and that differential gene expression analysis is a good approach to select candidate biomarkers to set up blood assays cancer screening. PMID:20068563

  16. Non-invasive molecular profiling of cancer using photoacoustic imaging of functionalized gold nanorods

    NASA Astrophysics Data System (ADS)

    Shah, Anant J.; Alles, Erwin J.; Box, Carol; Eccles, Suzanne A.; Robinson, Simon P.; deSouza, Nandita; Bamber, Jeffrey C.

    2014-03-01

    Although molecularly targeted cancer therapies have shown great promise, it is now evident that responses are dependent upon the molecular genetic context. Spatial and temporal tumour heterogeneity renders biopsy of solid tumours unsuitable for determining the genetic profile of the disease, making adaptation of appropriate therapy difficult. We have utilized the tunable optical absorption characteristic of gold nanorods to assess the potential of photoacoustics for non-invasive multiplexed molecular imaging. Gold nanorods with resonance peaks at 700nm and 900nm were functionalised with in-house antibodies ICR55 and ICR62, targeted to HER2 and EGFR transmembrane receptors, respectively. Three human squamous carcinoma cell lines (LICR-LON-HN4 expressing high HER2 and low EGFR, LICR-LON-HN3 expressing intermediate levels of HER2 and EGFR and A431 expressing high EGFR and low HER2) were incubated with the targeted nanorods for 24 hours. Cells were then incorporated as simulated tumours in tissue-like phantoms composed of 7.5% gelatin containing 0.5% Intralipid® for optical scattering and imaged at a depth of 2.5 cm, using a new clinical in-house multi-spectral photoacoustic imaging system. Images were obtained from the cell inclusions for wavelengths ranging from 710 to 950 nm at 40 nm intervals, and the mean amplitude of the photoacoustic image was computed for each wavelength, to determine their relative receptor expression levels. The molecular profile of the cells obtained using multi-wavelength photoacoustics had substantial similarity to that obtained using flow cytometry. These preliminary results confirm selective uptake of the functionalised nanorods, which reflects the cellular expression of therapeutically important oncoproteins, and give an indication of the potential of photoacoustics for multiplexed molecular profiling.

  17. Gene expression profile predictive of response to chemotherapy in metastatic colorectal cancer.

    PubMed

    Estevez-Garcia, Purificacion; Rivera, Fernando; Molina-Pinelo, Sonia; Benavent, Marta; Gómez, Javier; Limón, Maria Luisa; Pastor, Maria Dolores; Martinez-Perez, Julia; Paz-Ares, Luis; Carnero, Amancio; Garcia-Carbonero, Rocio

    2015-03-20

    Fluoropyrimidine-based chemotherapy (CT) has been the mainstay of care of metastatic colorectal cancer (mCRC) for years. Response rates are only observed, however, in about half of treated patients, and there are no reliable tools to prospectively identify patients more likely to benefit from therapy. The purpose of our study was to identify a gene expression profile predictive of CT response in mCRC. Whole genome expression analyses (Affymetrix GeneChip HG-U133 Plus 2.0) were performed in fresh frozen tumor samples of 37 mCRC patients (training cohort). Differential gene expression profiles among the two study conditions (responders versus non-responders) were assessed using supervised class prediction algorithms. A set of 161 differentially expressed genes in responders (23 patients; 62%) versus non-responders (14 patients; 38%) was selected for further assessment and validation by RT-qPCR (TaqMan Low Density Arrays (TLDA) 7900 HT Micro Fluidic Cards) in an independent multi-institutional cohort (53 mCRC patients). Seven of these genes were confirmed as significant predictors of response. Patients with a favorable predictive signature had significantly greater response rate (58% vs. 13%, p = 0.024), progression-free survival (61% vs. 13% at 1 year, HR = 0.32, p = 0.009) and overall survival (32 vs. 16 months, HR = 0.21, p = 0.003) than patients with an unfavorable gene signature. This is the first study to validate a gene-expression profile predictive of response to CT in mCRC patients. Larger and prospective confirmatory studies are required, however, in order to successfully provide oncologists with adequate tools to optimize treatment selection in routine clinical practice.

  18. Reflexology versus Swedish Massage to Reduce Physiologic Stress and Pain and Improve Mood in Nursing Home Residents with Cancer: A Pilot Trial

    PubMed Central

    Hodgson, Nancy A.; Lafferty, Doreen

    2012-01-01

    Objective. The purpose of this pilot study was to investigate and compare the effects of reflexology and Swedish massage therapy on physiologic stress, pain, and mood in older cancer survivors residing in nursing homes. Methods. An experimental, repeated-measures, crossover design study of 18 nursing home residents aged 75 or over and diagnosed with solid tumor in the past 5 years and following completion of cancer treatments. The intervention tested was 20 minutes of Swedish Massage Therapy to the lower extremities, versus 20 minute Reflexology, using highly specified protocols. Pre- and post-intervention levels of salivary cortisol, observed affect, and pain were compared in the Swedish Massage Therapy and Reflexology conditions. Results. Both Reflexology and Swedish Massage resulted in significant declines in salivary cortisol and pain and improvements in mood. Conclusions. Preliminary data suggest that studies of Swedish Massage Therapy and Reflexology are feasible in this population of cancer survivors typically excluded from trials. Both interventions were well tolerated and produced measurable improvements in outcomes. Further research is needed to explore the mechanisms underlying the potential benefits of these CAM modalities in this patient population. PMID:22888364

  19. Reflexology versus Swedish Massage to Reduce Physiologic Stress and Pain and Improve Mood in Nursing Home Residents with Cancer: A Pilot Trial.

    PubMed

    Hodgson, Nancy A; Lafferty, Doreen

    2012-01-01

    Objective. The purpose of this pilot study was to investigate and compare the effects of reflexology and Swedish massage therapy on physiologic stress, pain, and mood in older cancer survivors residing in nursing homes. Methods. An experimental, repeated-measures, crossover design study of 18 nursing home residents aged 75 or over and diagnosed with solid tumor in the past 5 years and following completion of cancer treatments. The intervention tested was 20 minutes of Swedish Massage Therapy to the lower extremities, versus 20 minute Reflexology, using highly specified protocols. Pre- and post-intervention levels of salivary cortisol, observed affect, and pain were compared in the Swedish Massage Therapy and Reflexology conditions. Results. Both Reflexology and Swedish Massage resulted in significant declines in salivary cortisol and pain and improvements in mood. Conclusions. Preliminary data suggest that studies of Swedish Massage Therapy and Reflexology are feasible in this population of cancer survivors typically excluded from trials. Both interventions were well tolerated and produced measurable improvements in outcomes. Further research is needed to explore the mechanisms underlying the potential benefits of these CAM modalities in this patient population.

  20. Shear-wave elastography of invasive breast cancer: correlation between quantitative mean elasticity value and immunohistochemical profile.

    PubMed

    Youk, Ji Hyun; Gweon, Hye Mi; Son, Eun Ju; Kim, Jeong-Ah; Jeong, Joon

    2013-02-01

    To compare the mean elasticity value, as measured by shear-wave elastography (SWE), with immunohistochemical profile of invasive breast cancer. This was an institutional review board-approved retrospective study, with a waiver of informed consent. A total of 166 invasive breast cancers in 152 women undergoing preoperative SWE and surgery were included. Quantitative mean elasticity values in kPa were measured for each lesion by using SWE. Medical records were reviewed to determine palpability, invasive size, lymphovascular invasion, histologic grade, and axillary lymph node status. Based on the immunohistochemical profiles, tumor subtypes were categorized as triple-negative (TN), luminal A and B, or human epidermal growth factor receptor 2-enriched cancer. The mean elasticity value was correlated with clinicopathological features using univariate regression models and multivariate linear regression analysis. Palpability (P < 0.0001), larger size (P = 0.013), lymphovascular invasion (P < 0.0001), higher histologic grade (P < 0.0001), and lymph node involvement (P = 0.018) were significantly associated with the mean elasticity value. For the immunohistochemical profiles and tumor subtypes, the estrogen receptor (P = 0.015), progesterone receptor (P = 0.002), Ki-67 (P = 0.009), and the TN (P = 0.009) tumor subtype were correlated with the mean elasticity value. Multivariate logistic regression analysis showed that the following variables were significantly associated with the mean elasticity value: palpable abnormality, histologic grade, and lymphovascular invasion. No immunohistochemical profile of the cancers was independently correlated with the mean elasticity value. For invasive breast cancers, clinicopathological features of poor prognosis showed higher mean elasticity values than those of good prognosis. However, the immunohistochemical profile showed no independent association with the mean elasticity value.

  1. Thyroid Cancer

    MedlinePlus

    ... are here Home > Types of Cancer > Thyroid Cancer Thyroid Cancer This is Cancer.Net’s Guide to Thyroid Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Thyroid Cancer Introduction Statistics Medical Illustrations Risk Factors Symptoms and ...

  2. [Assessment of our home care and home palliative care].

    PubMed

    Midorikawa, Yasuhiko; Suzushino, Seiko; Tamotsu, Kiyokazu

    2014-12-01

    We conducted home care and home palliative care from the department of home care. We provided home care services to 190 patients(105 men, 85 women)in October 2013. Their average age was 78.7(range: 32-102)years old, and home care had been underway from 1 day to 8 years, 10 months. Among all participants, 168(88.4%)suffered from malignant diseases, 168 patients had died, and over half of deceased patients(88 out of 168)had died at home. We used opioids for control of cancer pain, carried out home parenteral nutrition(HPN), home enteral nutrition(HEN), percutaneous endoscopic gastrostomy( PEG), and removed pleural effusion and ascites during home care. In order to facilitate the practice of palliative care by the palliative care team, which consists of various medical staff in the hospital, we are giving high priority to education and enlightenment in the hospital. To provide enlightenment, education, and cooperation between regional home care and home palliative care, we are also conducting educational lectures in the regional party of the Iwaki city medical associate, and providing combined educational-medical training for home care and home palliative care by various medical staff.

  3. “Picking up the pieces”—Meanings of receiving home nursing care when being old and living with advanced cancer in a rural area

    PubMed Central

    Devik, Siri Andreassen; Hellzen, Ove; Enmarker, Ingela

    2015-01-01

    Rural home nursing care is a neglected area in the research of palliative care offered to older cancer patients. Because access to specialized services is hampered by long distances and fragmented infrastructure, palliative care is often provided through standard home nursing services and delivered by general district nurses. This study aimed to illuminate the lived experience and to interpret the meaning of receiving home nursing care when being old and living with advanced cancer in a rural area in Norway. Narrative interviews were conducted with nine older persons, and a phenomenological hermeneutic approach was used to interpret the meaning of the lived experience. The analysis revealed three themes, each with subthemes: being content with what one gets, falling into place, and losing one's place. The phrase picking up the pieces was found useful to sum up the meaning of this lived experience. The three respective themes refer to how the pieces symbolize the remaining parts of life or available services in their environment, and how the older persons may see themselves as pieces or bricks in a puzzle. A strong place attachment (physical insideness, social insideness, and autobiographical insideness) is demonstrated by the informants in this study and suggests that the rural context may provide an advantageous healthcare environment. Its potential to be a source of comfort, security, and identity concurs with cancer patients’ strong desire for being seen as unique persons. The study shows that district nurses play an essential role in the provision of palliative care for older rural patients. However, the therapeutic value of being in one's familiar landscape seems to depend on how homecare nurses manage to locate it and use it in a more or less person-centred manner. Communication skills and attentiveness to psychosocial aspects of patient care stand out as important attributes for nursing in this context. PMID:26362533

  4. Profiling Global Kinome Signatures of the Radioresistant MCF-7/C6 Breast Cancer Cells Using MRM-based Targeted Proteomics

    PubMed Central

    2015-01-01

    Ionizing radiation is widely used in cancer therapy; however, cancer cells often develop radioresistance, which compromises the efficacy of cancer radiation therapy. Quantitative assessment of the alteration of the entire kinome in radioresistant cancer cells relative to their radiosensitive counterparts may provide important knowledge to define the mechanism(s) underlying tumor adaptive radioresistance and uncover novel target(s) for effective prevention and treatment of tumor radioresistance. By employing a scheduled multiple-reaction monitoring analysis in conjunction with isotope-coded ATP affinity probes, we assessed the global kinome of radioresistant MCF-7/C6 cells and their parental MCF-7 human breast cancer cells. We rigorously quantified 120 kinases, of which 1/3 exhibited significant differences in expression levels or ATP binding affinities. Several kinases involved in cell cycle progression and DNA damage response were found to be overexpressed or hyperactivated, including checkpoint kinase 1 (CHK1), cyclin-dependent kinases 1 and 2 (CDK1 and CDK2), and the catalytic subunit of DNA-dependent protein kinase. The elevated expression of CHK1, CDK1, and CDK2 in MCF-7/C6 cells was further validated by Western blot analysis. Thus, the altered kinome profile of radioresistant MCF-7/C6 cells suggests the involvement of kinases on cell cycle progression and DNA repair in tumor adaptive radioresistance. The unique kinome profiling results also afforded potential effective targets for resensitizing radioresistant cancer cells and counteracting deleterious effects of ionizing radiation exposure. PMID:25341124

  5. Genetics Home Reference: Simpson-Golabi-Behmel syndrome

    MedlinePlus

    ... Wilms tumor and a cancerous tumor called a neuroblastoma that arises in developing nerve cells. Related Information ... National Cancer Institute: Kidney Cancer National Cancer Institute: Neuroblastoma Home Page Educational Resources (3 links) Disease InfoSearch: ...

  6. [Search for potential gastric cancer biomarkers using low molecular weight blood plasma proteome profiling by mass spectrometry].

    PubMed

    Shevchenko, V E; Arnotskaia, N E; Ogorodnikova, E V; Davydov, M M; Ibraev, M A; Turkin, I N; Davydov, M I

    2014-01-01

    Gastric cancer, one of the most widespread malignant tumors, still lacks reliable serum/plasma biomarkers of its early detection. In this study we have developed, unified, and tested a new methodology for search of gastric cancer biomarkers based on profiling of low molecular weight proteome (LMWP) (1-17 kDa). This approach included three main components: sample pre-fractionation, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), data analysis by a bioinformatics software package. Applicability and perspectives of the developed approach for detection of potential gastric cancer markers during LMWP analysis have been demonstrated using 69 plasma samples from patients with gastric cancer (stages I-IV) and 238 control samples. The study revealed peptides/polypeptides, which may be potentially used for detection of this pathology.

  7. Global tyrosine kinome profiling of human thyroid tumors identifies Src as a promising target for invasive cancers

    SciTech Connect

    Cho, Nancy L.; Lin, Chi-Iou; Du, Jinyan; Whang, Edward E.; Ito, Hiromichi; Moore, Francis D.; Ruan, Daniel T.

    2012-05-11

    Highlights: Black-Right-Pointing-Pointer Kinome profiling is a novel technique for identifying activated kinases in human cancers. Black-Right-Pointing-Pointer Src activity is increased in invasive thyroid cancers. Black-Right-Pointing-Pointer Inhibition of Src activity decreased proliferation and invasion in vitro. Black-Right-Pointing-Pointer Further investigation of Src targeted therapies in thyroid cancer is warranted. -- Abstract: Background: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using a bead-based, high-throughput system. Methods: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room. Protein lysates were analyzed using the Luminex immunosandwich, a bead-based kinase phosphorylation assay. Data was analyzed using GenePattern 3.0 software and clustered according to histology, demographic factors, and tumor status regarding capsular invasion, size, lymphovascular invasion, and extrathyroidal extension. Survival and invasion assays were performed to determine the effect of Src inhibition in papillary thyroid cancer (PTC) cells. Results: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Supervised clustering of well-differentiated tumors by histology, gender, age, or size did not reveal significant differences in tyrosine kinase activity. However, supervised clustering by the presence of invasive disease showed increased Src activity in invasive tumors relative to non-invasive tumors (60% v. 0%, p < 0.05). In vitro, we found that Src inhibition in PTC cells decreased cell invasion and proliferation

  8. Profiles of miRNAs matched to biology in aromatase inhibitor resistant breast cancer

    PubMed Central

    Hoppe, Reiner; Fan, Ping; Büttner, Florian; Winter, Stefan; Tyagi, Amit K.; Cunliffe, Heather; Jordan, V. Craig; Brauch, Hiltrud

    2016-01-01

    Aromatase inhibitor (AI) resistance during breast cancer treatment is mimicked by MCF-7:5C (5C) and MCF-7:2A (2A) cell lines that grow spontaneously. Survival signaling is reconfigured but cells are vulnerable to estradiol (E2)-inducible apoptosis. These model systems have alterations of stress related pathways including the accumulation of endoplasmic reticulum, oxidative, and inflammatory stress that occur prior to E2-induced apoptosis. We investigated miRNA expression profiles of 5C and 2A to characterize their AI resistance phenotypes. Affymetrix GeneChip miRNA2.0 arrays identified 184 miRNAs differentially expressed in 2A and 5C compared to E2-free wild-type MCF-7:WS8. In 5C, 34 miRNAs of the DLK1-DIO3 locus and miR-31 were overexpressed, whereas miR-222 was low. TCGA data revealed poor and favorable overall survival for low miR-31 and miR-222 levels, respectively (HR=3.0, 95% CI:1.9-4.8; HR=0.3, 95% CI:0.1-0.6). Targets of deregulated miRNAs were identified using CLIP-confirmed TargetScan predictions. KEGG enrichment analyses for 5C- and 2A-specific target gene sets revealed pathways associated with cell proliferation including insulin, mTOR, and ErbB signaling as well as immune response and metabolism. Key genes overrepresented in 5C- and 2A-specific pathway interaction networks including EGFR, IGF1R and PIK3R1 had lower protein levels in 5C compared to 2A and were found to be differentially modulated by respective miRNA sets. Distinct up-regulated miRNAs from the DLK1-DIO3 locus may cause these attenuative effects as they are predicted to interact with corresponding 3′ untranslated regions. These new miRNA profiles become an important regulatory database to explore E2-induced apoptotic mechanisms of clinical relevance for the treatment of resistant breast cancer. PMID:27659519

  9. Kidney Cancer

    MedlinePlus

    ... common cancers in the United States. Cancer Home Kidney Cancer Language: English Español (Spanish) Recommend on Facebook ... work with the chemical trichloroethylene. What Are the Kidneys? The body has two kidneys, one on each ...

  10. Different mutation profiles associated to P53 accumulation in colorectal cancer.

    PubMed

    López, Ignacio; P Oliveira, Ligia; Tucci, Paula; Alvarez-Valín, Fernando; A Coudry, Renata; Marín, Mónica

    2012-05-10

    The tumor suppressor TP53 gene is one of the most frequently mutated in different types of human cancer. Particularly in colorectal cancer (CRC), it is believed that TP53 mutations play a role in the adenoma-carcinoma transition of tumors during pathological process. In order to analyze TP53 expressed alleles in CRC, we examined TP53 mRNA in tumor samples from 101 patients with sporadic CRC. Samples were divided in two groups defined according to whether they exhibit positive or negative P53 protein expression as detected by immunohistochemistry (IHC). The presence of TP53 mutation was a common event in tumors with an overall frequency of 54.5%. By direct sequencing, we report 42 different TP53 sequence changes in 55 CRC patients, being two of them validated polymorphisms. TP53 mutations were more frequent in positive than in negative P53 detection group (p<0.0001), being the precise figures 79.6% and 30.8%, respectively. In addition, the mutation profiles were also different between the two groups of samples; while most of the mutations detected in P53 positive group were missense (38 out of 39), changes in P53 negative detection group include 7 insertions/deletions, 6 missense, 2 nonsense and 1 silent mutation. As previously observed, most mutations were concentrated in regions encoding P53 DNA binding domain (DBD). Codons 175, 248 and 273 together account for 36.7% of point mutations, in agreement with previous observations provided that these codons are considered mutation hotspots. Interestingly, we detected two new deletions and two new insertions. In addition, in three samples we detected two deletions and one insertion that could be explained as putative splicing variants or splicing errors.

  11. Profiling of Cross-Functional Peptidases Regulated Circulating Peptides in BRCA1 Mutant Breast Cancer

    PubMed Central

    Fan, Jia; Tea, Muy-Kheng M.; Yang, Chuan; Ma, Li; Meng, Qing H.; Hu, Tony Y.; Singer, Christian F.; Ferrari, Mauro

    2016-01-01

    Women with inherited BRCA1 mutations are more likely to develop breast cancer (BC); however, not every carrier will progress to BC. The aim of this study was to identify and characterize circulating peptides that correlate with BC patients carrying BRCA1 mutations. Circulating peptides were enriched using our well-designed nanoporous silica thin films (NanoTraps) and profiled by mass spectrometry to identify among four clinical groups. To determine the corresponding proteolytic processes and their sites of activity, purified candidate peptidases and synthesized substrates were assayed to verify the processes predicted by the MERPOS database. Proteolytic processes were validated using patient serum samples. The peptides, KNG1K438-R457 and C 3fS1304-R1320, were identified as putative peptide candidates to differentiate BRCA1 mutant BC from sporadic BC and cancer-free BRCA1 mutant carriers. Kallikrein-2 (KLK2) is the major peptidase that cleaves KNG1K438-R457 from kininogen-1, and its expressions and activities were also found to be dependent on BRCA1 status. We further determined that KNG1K438-R457 is cleaved at its C-terminal arginine by carboxypeptidase N1 (CPN1). Increased KLK2 activity, with decreased CPN1 activity, results in the accumulation of KNG1K438-R457 in BRCA1-associated BC. Our work outlined a useful strategy for determining the peptide–petidase relationship and thus establishing a biological mechanism for changes in the peptidome in BRCA1-associated BC. PMID:27058005

  12. Economic Impact of Gene Expression Profiling in Patients with Early-Stage Breast Cancer in France

    PubMed Central

    Katz, Gregory; Romano, Olivier; Foa, Cyril; Vataire, Anne-Lise; Chantelard, Jean-Victor; Hervé, Robert; Barletta, Hugues; Durieux, Axel; Martin, Jean-Pierre; Salmon, Rémy

    2015-01-01

    Background and Aims The heterogeneous nature of breast cancer can make decisions on adjuvant chemotherapy following surgical resection challenging. Oncotype DX is a validated gene expression profiling test that predicts the likelihood of adjuvant chemotherapy benefit in early-stage breast cancer. The aim of this study is to determine the costs of chemotherapy in private hospitals in France, and evaluate the cost-effectiveness of Oncotype DX from national insurance and societal perspectives. Methods A multicenter study was conducted in seven French private hospitals, capturing retrospective data from 106 patient files. Cost estimates were used in conjunction with a published Markov model to assess the cost-effectiveness of using Oncotype DX to inform chemotherapy decision making versus standard care. Sensitivity analyses were performed. Results The cost of adjuvant chemotherapy in private hospitals was estimated at EUR 8,218 per patient from a national insurance perspective and EUR 10,305 from a societal perspective. Cost-effectiveness analysis indicated that introducing Oncotype DX improved life expectancy (+0.18 years) and quality-adjusted life expectancy (+0.17 QALYs) versus standard care. Oncotype DX was found cost-effective from a national insurance perspective (EUR 2,134 per QALY gained) and cost saving from a societal perspective versus standard care. Inclusion of lost productivity costs in the modeling analysis meant that costs for eligible patients undergoing Oncotype DX testing were on average EUR 602 lower than costs for those receiving standard care. Conclusions As Oncotype DX was found both cost and life-saving from a societal perspective, the test was considered to be dominant to standard care. However, the delay in coverage has the potential to erode the quality of the French healthcare system, thus depriving patients of technologies that could improve clinical outcomes and allow healthcare professionals to better allocate hospital resources to

  13. Breakpoint profiling of 64 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms

    PubMed Central

    Malhotra, Ankit; Lindberg, Michael; Faust, Gregory G.; Leibowitz, Mitchell L.; Clark, Royden A.; Layer, Ryan M.; Quinlan, Aaron R.; Hall, Ira M.

    2013-01-01

    Tumor genomes are generally thought to evolve through a gradual accumulation of mutations, but the observation that extraordinarily complex rearrangements can arise through single mutational events suggests that evolution may be accelerated by punctuated changes in genome architecture. To assess the prevalence and origins of complex genomic rearrangements (CGRs), we mapped 6179 somatic structural variation breakpoints in 64 cancer genomes from seven tumor types and screened for clusters of three or more interconnected breakpoints. We find that complex breakpoint clusters are extremely common: 154 clusters comprise 25% of all somatic breakpoints, and 75% of tumors exhibit at least one complex cluster. Based on copy number state profiling, 63% of breakpoint clusters are consistent with being CGRs that arose through a single mutational event. CGRs have diverse architectures including focal breakpoint clusters, large-scale rearrangements joining clusters from one or more chromosomes, and staggeringly complex chromothripsis events. Notably, chromothripsis has a significantly higher incidence in glioblastoma samples (39%) relative to other tumor types (9%). Chromothripsis breakpoints also show significantly elevated intra-tumor allele frequencies relative to simple SVs, which indicates that they arise early during tumorigenesis or confer selective advantage. Finally, assembly and analysis of 4002 somatic and 6982 germline breakpoint sequences reveal that somatic breakpoints show significantly less microhomology and fewer templated insertions than germline breakpoints, and this effect is stronger at CGRs than at simple variants. These results are inconsistent with replication-based models of CGR genesis and strongly argue that nonhomologous repair of concurrently arising DNA double-strand breaks is the predominant mechanism underlying complex cancer genome rearrangements. PMID:23410887

  14. Expression profile of long non-coding RNAs in colorectal cancer: A microarray analysis.

    PubMed

    Luo, Jia; Xu, Luning; Jiang, Yigui; Zhuo, Dexiang; Zhang, Shengjun; Wu, Lianhui; Xu, Huadong; Huang, Yue

    2016-04-01

    Colorectal cancer (CRC) is one of the most prevalent malignant tumors and the second cause of cancer-related mortality worldwide. Due to increased morbidity and mortality rates, there is an urgent need to understand the pathogenesis of CRC, discover strategies that can improve diagnosis, and ultimately identify therapies targeting this disease. Over the past several years, research into tumor progression mechanisms has been devoted to identifying and understanding various coding and non-coding regions of the genome and how these genetic variants may affect tumorigenesis and progression. Recently, long non-coding RNAs (lncRNAs), which are non‑protein coding transcripts longer than 200 nucleotides, have emerged as a key aspect in tumor pathogenesis. In the present study, we examined the lncRNA and mRNA expression profiles in 4 patients with colon adenocarcinoma, with paired adjacent normal tissues as controls. Microarray data showed that a total of 3,523 lncRNAs and 2,515 mRNAs were consistently differentially expressed in the CRC tissues compared to adjacent normal tissues. Upon comparison of the differentially expressed transcripts between the groups, we identified 22 pathways which were related to the upregulated transcripts and 24 pathways that corresponded to the downregulated transcripts. Gene ontology analysis revealed that the upregulated transcripts were predominantly enriched in DNA metabolic processes, and the downregulated transcripts were predominantly enriched in organic hydroxyl compound metabolic processes. Coding-non-coding gene co-expression analysis showed that these differentially expressed lncRNAs were closely correlated with 'Wnt signaling pathway' components, whose aberrant activation plays a central role in CRC, indicating that a functional correlation exists between them. In conclusion, the results of the microarray and informatic analysis strongly suggest that lncRNA dysregulation is involved in the complicated process of CRC development

  15. Clinical Relevance of the First Domomedicine Platform Securing Multidrug Chronotherapy Delivery in Metastatic Cancer Patients at Home: The inCASA European Project

    PubMed Central

    Innominato, Pasquale F; Komarzynski, Sandra; Mohammad-Djafari, Ali; Arbaud, Alexandre; Ulusakarya, Ayhan; Bouchahda, Mohamed; Haydar, Mazen; Bossevot-Desmaris, Rachel; Plessis, Virginie; Mocquery, Magali; Bouchoucha, Davina; Afshar, Mehran; Beau, Jacques; Karaboué, Abdoulaye; Morère, Jean-François; Fursse, Joanna; Rovira Simon, Jordi

    2016-01-01

    Background Telehealth solutions can improve the safety of ambulatory chemotherapy, contributing to the maintenance of patients at their home, hence improving their well-being, all the while reducing health care costs. There is, however, need for a practicable multilevel monitoring solution, encompassing relevant outputs involved in the pathophysiology of chemotherapy-induced toxicity. Domomedicine embraces the delivery of complex care and medical procedures at the patient’s home based on modern technologies, and thus it offers an integrated approach for increasing the safety of cancer patients on chemotherapy. Objective The objective was to evaluate patient compliance and clinical relevance of a novel integrated multiparametric telemonitoring domomedicine platform in cancer patients receiving multidrug chemotherapy at home. Methods Self-measured body weight, self-rated symptoms using the 19-item MD Anderson Symptom Inventory (MDASI), and circadian rest-activity rhythm recording with a wrist accelerometer (actigraph) were transmitted daily by patients to a server via the Internet, using a dedicated platform installed at home. Daily body weight changes, individual MDASI scores, and relative percentage of activity in-bed versus out-of-bed (I

  16. Mapping MRI/MRS Parameters with Genetic Over-expression Profiles In Human Prostate Cancer: Demonstrating the Potential

    PubMed Central

    Lenkinski, Robert E.; Bloch, B. Nicholas; Liu, Fangbing; Frangioni, John V.; Perner, Sven; Rubin, Mark A.; Genega, Elizabeth; Rofsky, Neil M.; Gaston, Sandra M.

    2009-01-01

    Magnetic resonance imaging (MRI) and MR spectroscopy can probe a variety of physiological (e.g. blood vessel permeability) and metabolic characteristics of prostate cancer. However, little is known about the changes in gene expression that underlie the spectral and imaging features observed in prostate cancer. Tumor induced changes in vascular permeability and angiogenesis are thought to contribute to patterns of dynamic contrast enhanced (DCE) MRI images of prostate cancer even though the genetic basis of tumor vasculogenesis is complex and the specific mechanisms underlying these DCEMRI features have not yet been determined. In order to identify the changes in gene expression that correspond to MRS and DCEMRI patterns in human prostate cancers, we have utilized tissue print micropeel techniques to generate “whole mount” molecular maps of radical prostatectomy specimens that correspond to pre-surgical MRI/MRS studies. These molecular maps include RNA expression profiles from both Affymetrix GeneChip microarrays and quantitative reverse transcriptase PCR (qrt-PCR) analysis, as well as immunohistochemical studies. Using these methods on patients with prostate cancer, we found robust over-expression of choline kinase a in the majority of primary tumors. We also observed overexpression of neuropeptide Y (NPY), a newly identified angiogenic factor, in a subset of DCEMRI positive prostate cancers. These studies set the stage for establishing MRI/MRS parameters as validated biomarkers for human prostate cancer. PMID:18752015

  17. [DNA microarray-based gene expression profiling in diagnosis, assessing prognosis and predicting response to therapy in colorectal cancer].

    PubMed

    Kwiatkowski, Przemysław; Wierzbicki, Piotr; Kmieć, Andrzej; Godlewski, Janusz

    2012-06-11

     Colorectal cancer is the most common cancer of the gastrointestinal tract. It is considered as a biological model of a certain type of cancerogenesis process in which progression from an early to late stage adenoma and cancer is accompanied by distinct genetic alterations. Clinical and pathological parameters commonly used in clinical practice are often insufficient to determine groups of patients suitable for personalized treatment. Moreover, reliable molecular markers with high prognostic value have not yet been determined. Molecular studies using DNA-based microarrays have identified numerous genes involved in cell proliferation and differentiation during the process of cancerogenesis. Assessment of the genetic profile of colorectal cancer using the microarray technique might be a useful tool in determining the groups of patients with different clinical outcomes who would benefit from additional personalized treatment. The main objective of this study was to present the current state of knowledge on the practical application of gene profiling techniques using microarrays for determining diagnosis, prognosis and response to treatment in colorectal cancer.

  18. What Is Lung Cancer?

    MedlinePlus

    ... Graphics Infographic Stay Informed Cancer Home What Is Lung Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet ... cancer starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may ...

  19. Cancer during Pregnancy

    MedlinePlus

    ... Cancer is Treated Side Effects Dating, Sex, and Reproduction Dating and Intimacy Sexuality and Cancer Treatment: Men ... here Home > Navigating Cancer Care > Dating, Sex, and Reproduction > Cancer During Pregnancy Request Permissions Cancer During Pregnancy ...

  20. 6 Common Cancers - Prostate Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

  1. Genetics Home Reference: Laron syndrome

    MedlinePlus

    ... AL. Obesity, diabetes and cancer: insight into the relationship from a cohort with growth hormone receptor deficiency. ... healthcare professional . About Genetics Home Reference Site Map Customer Support Selection Criteria for Links USA.gov Copyright ...

  2. Cell Line Derived 5-FU and Irinotecan Drug-Sensitivity Profiles Evaluated in Adjuvant Colon Cancer Trial Data

    PubMed Central

    Delorenzi, Mauro; Jensen, Thomas; Jensen, Peter Buhl; Bosman, Fred; Tejpar, Sabine; Roth, Arnaud; Brunner, Nils; Hansen, Anker; Knudsen, Steen

    2016-01-01

    Purpose This study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs. Methods To test if an irinotecan signature and a SN-38 signature could identify patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based on cell lines and clinical tumor material. These profiles were applied to expression data obtained from pretreatment formalin fixed paraffin embedded (FFPE) tumor tissue from 636 stage III colon cancer patients enrolled in the PETACC-3 prospective randomized clinical trial. A 5-FU profile developed similarly was assessed by comparing the PETACC-3 cohort with a cohort of 359 stage II colon cancer patients who underwent surgery but received no adjuvant therapy. Results There was no statistically significant association between the irinotecan or SN-38 profiles and benefit from irinotecan. The 5-FU sensitivity profile showed a statistically significant association with relapse free survival (RFS) (hazard ratio (HR) = 0.54 (0.41–0.71), p<1e-05) and overall survival (HR = 0.47 (0.34–0.63), p<1e-06) in the PETACC-3 subpopulation. The effect of the 5-FU profile remained significant in a multivariable Cox Proportional Hazards model, adjusting for several relevant clinicopathological parameters. No statistically significant effect of the 5-FU profile was observed in the untreated cohort of 359 patients (relapse free survival, p = 0.671). Conclusion The irinotecan predictor had no predictive value. The 5-FU predictor was prognostic in stage III patients in PETACC-3 but not in stage II patients with no adjuvant therapy. This suggests a potential predictive ability of the 5-FU sensitivity profile to identify colon cancer patients who may benefit from 5-FU, however, any biomarker predicting benefit for adjuvant 5-FU must be rigorously evaluated in independent cohorts. Given differences

  3. DNA methylation profiling to assess pathogenicity of BRCA1 unclassified variants in breast cancer.

    PubMed

    Flower, Kirsty J; Shenker, Natalie S; El-Bahrawy, Mona; Goldgar, David E; Parsons, Michael T; Spurdle, Amanda B; Morris, Joanna R; Brown, Robert; Flanagan, James M

    2015-01-01

    Germline pathogenic mutations in BRCA1 increase risk of developing breast cancer. Screening for mutations in BRCA1 frequently identifies sequence variants of unknown pathogenicity and recent work has aimed to develop methods for determining pathogenicity. We previously observed that tumor DNA methylation can differentiate BRCA1-mutated from BRCA1-wild type tumors. We hypothesized that we could predict pathogenicity of variants based on DNA methylation profiles of tumors that had arisen in carriers of unclassified variants. We selected 150 FFPE breast tumor DNA samples [47 BRCA1 pathogenic mutation carriers, 65 BRCAx (BRCA1-wild type), 38 BRCA1 test variants] and analyzed a subset (n=54) using the Illumina 450K methylation platform, using the remaining samples for bisulphite pyrosequencing validation. Three validated markers (BACH2, C8orf31, and LOC654342) were combined with sequence bioinformatics in a model to predict pathogenicity of 27 variants (independent test set). Predictions were compared with standard multifactorial likelihood analysis. Prediction was consistent for c.5194-12G>A (IVS 19-12 G>A) (P>0.99); 13 variants were considered not pathogenic or likely not pathogenic using both approaches. We conclude that tumor DNA methylation data alone has potential to be used in prediction of BRCA1 variant pathogenicity but is not independent of estrogen receptor status and grade, which are used in current multifactorial models to predict pathogenicity.

  4. MicroRNA expression profiling in male and female familial breast cancer

    PubMed Central

    Pinto, R; De Summa, S; Danza, K; Popescu, O; Paradiso, A; Micale, L; Merla, G; Palumbo, O; Carella, M; Tommasi, S

    2014-01-01

    Background: Gender-associated epigenetic alterations are poorly investigated in male and female familial breast cancer (fBC). MicroRNAs may contribute to the different biology in men and women particularly related to RASSF1A pathways. Methods: Microarray technology was used to evaluate miRNA profile in 24 male and 43 female fBC. Key results were validated using RT–qPCR in an external samples set. In vitro studies were carried out to verify microRNA–target gene interaction. Results: Pathway enrichment analysis with the 287 differentially expressed microRNAs revealed several signalling pathways differently regulated in male and female cases. Because we previously hypothesised a peculiar involvement of RASSF1A in male fBC pathogenesis, we focussed on the MAPK and the Hippo signalling pathways that are regulated by RASSF1A. Male miR-152 and miR-497 upregulation and RASSF1A and NORE1A interacting gene downregulation were observed, confirming a possible indirect interaction between miRNAs and the two genes. Conclusions: For the first time, a different microRNA expression pattern in male and female fBC has been shown. Moreover, the importance of RASSF1A pathway in male fBC carcinogenesis has been confirmed, highlighting a possible role for miR-152 and miR-497 in controlling MAPK and Hippo signalling pathways, regulated by RASSF1A. PMID:25393370

  5. Lipidomic Profiling of Adipose Tissue Reveals an Inflammatory Signature in Cancer-Related and Primary Lymphedema

    PubMed Central

    Sedger, Lisa M.; Tull, Dedreia L.; McConville, Malcolm J.; De Souza, David P.; Rupasinghe, Thusitha W. T.; Williams, Spencer J.; Dayalan, Saravanan; Lanzer, Daniel; Mackie, Helen; Lam, Thomas C.; Boyages, John

    2016-01-01

    Cancer-related and primary lymphedema (LE) are associated with the production of adipose tissue (AT). Nothing is known, however, about the lipid-based molecules that comprise LE AT. We therefore analyzed lipid molecules in lipoaspirates and serum obtained from LE patients, and compared them to lipoaspirates from cosmetic surgery patients and healthy control cohort serum. LE patient serum analysis demonstrated that triglycerides, HDL- and LDL-cholesterol and lipid transport molecules remained within the normal range, with no alterations in individual fatty acids. The lipidomic analysis also identified 275 lipid-based molecules, including triacylglycerides, diacylglycerides, fatty acids and phospholipids in AT oil and fat. Although the majority of lipid molecules were present in a similar abundance in LE and non-LE samples, there were several small changes: increased C20:5-containing triacylglycerides, reduced C10:0 caprinic and C24:1 nervonic acids. LE AT oil also contained a signature of increased cyclopropane-type fatty acids and inflammatory mediators arachidonic acid and ceramides. Interestingly C20:5 and C22:6 omega-3-type lipids are increased in LE AT, correlating with LE years. Hence, LE AT has a normal lipid profile containing a signature of inflammation and omega-3-lipids. It remains unclear, however, whether these differences reflect a small-scale global metabolic disturbance or effects within localised inflammatory foci. PMID:27182733

  6. Profile of rociletinib and its potential in the treatment of non-small-cell lung cancer

    PubMed Central

    Tran, Phu N; Klempner, Samuel J

    2016-01-01

    Patients with non-small-cell lung cancer (NSCLC) harboring activating mutations in EGFR benefit from treatment with EGFR small-molecule tyrosine-kinase inhibitors. However, the development of acquired resistance to EGFR inhibitors is universal and limits treatment efficacy. Over half of patients receiving first-generation EGFR inhibitors (erlotinib and gefitinib) develop resistance via the gatekeeper EGFR T790M (EGFRT790M) mutation, and therapies able to overcome T790M-mediated resistance have been an unmet need in NSCLC. Rociletinib (CO-1686) is a third-generation small-molecule EGFR inhibitor with potent activity against EGFRT790M currently in advanced clinical development in NSCLC. Early clinical data suggested significant activity in EGFR-mutant NSCLC harboring T790M alterations. However, important questions regarding side-effect profile, comparability to competitor compounds, acquired resistance, EGFR-therapy sequencing, and combination therapies remain. Here, we review the available preclinical and clinical data for rociletinib, highlight the comparison to other third-generation EGFR inhibitors, and discuss resistance implications and future directions in NSCLC. PMID:28210165

  7. Molecular Profiling-Selected Therapy for Treatment of Advanced Pancreaticobiliary Cancer: A Retrospective Multicenter Study.

    PubMed

    Epelbaum, Ron; Shacham-Shmueli, Einat; Klein, Baruch; Agbarya, Abed; Brenner, Baruch; Brenner, Ronen; Gez, Eliahu; Golan, Talia; Hubert, Ayala; Purim, Ofer; Temper, Mark; Tepper, Ella; Voss, Andreas; Russell, Kenneth; Dvir, Addie; Soussan-Gutman, Lior; Stemmer, Salomon M; Geva, Ravit

    2015-01-01

    This multicenter cohort study assessed the impact of molecular profiling (MP) on advanced pancreaticobiliary cancer (PBC). The study included 30 patients treated with MP-guided therapy after failing ≥ 1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS) on MP-guided therapy and the PFS on the last therapy before MP was ≥ 1.3. The null hypothesis was that ≤ 15% of patients gain such benefit. Overall, ≥ 1 actionable (i.e., predictive of response to specific therapies) biomarker was identified/patient. Immunohistochemistry (the most commonly used method for guiding treatment decisions) identified 1-6 (median: 4) actionable biomarkers per patient. After MP, patients received 1-4 (median: 1) regimens/patient (most commonly, FOLFIRI/XELIRI). In a decision-impact analysis, of the 27 patients for whom treatment decisions before MP were available, 74.1% experienced a treatment decision change in the first line after MP. Twenty-four patients were evaluable for clinical outcome analysis; in 37.5%, the PFS ratio was ≥ 1.3. In one-sided exact binomial test versus the null hypothesis, P = 0.0015; therefore, the null hypothesis was rejected. In conclusion, our analysis demonstrated the feasibility, clinical decision impact, and potential clinical benefits of MP-guided therapy in advanced PBC.

  8. Cancer-specific MALDI-TOF profiles of blood serum and plasma: biological meaning and perspectives.

    PubMed

    Karpova, M A; Moshkovskii, S A; Toropygin, I Y; Archakov, A I

    2010-01-03

    MALDI-TOF mass-spectrometry has become a popular tool of cancer research during the last decade. High throughput and relative simplicity of this technology have made it attractive for biomarker discovery and validation across various platforms in blood serum/plasma. Many technical approaches have been developed for plasma/serum profiling including protein-chip based SELDI-TOF mass-spectrometry, purification of serum on magnetic beads, analysis of carrier-associated fraction and mass-spectrometric immunoassays. Extensive data about the identity of differential features detected on mass-spectra up to now makes it possible to draw conclusions about potency and perspectives of MALDI-TOF mass-spectrometry in this field. A great majority of identified differentially expressed proteins are either house-keeping or inflammatory proteins as well as their modifications or fragments. Discriminating ability of mass-spectra is likely to be based on differential modification and fragmentation patterns of abundant serum proteins reflecting activity of enzymes including proteases and their inhibitors.

  9. Metabolite profiling of (14)C-omacetaxine mepesuccinate in plasma and excreta of cancer patients.

    PubMed

    Nijenhuis, Cynthia M; Lucas, Luc; Rosing, Hilde; Robertson, Philmore; Hellriegel, Edward T; Schellens, Jan H M; Beijnen, And Jos H

    2016-12-01

    Omacetaxine mepesuccinate (hereafter referred to as omacetaxine) is a protein translation inhibitor approved by the US Food and Drug Administration for adult patients with chronic myeloid leukemia with resistance and/or intolerance to two or more tyrosine kinase inhibitors. The objective was to investigate the metabolite profile of omacetaxine in plasma, urine and faeces samples collected up to 72 h after a single 1.25-mg/m(2) subcutaneous dose of (14)C-omacetaxine in cancer patients. High-performance liquid chromatography mass spectrometry (MS) (high resolution) in combination with off-line radioactivity detection was used for metabolite identification. In total, six metabolites of omacetaxine were detected. The reactions represented were mepesuccinate ester hydrolysis, methyl ester hydrolysis, pyrocatechol conversion from the 1,3-dioxole ring. Unchanged omacetaxine was the most prominent omacetaxine-related compound in plasma. In urine, unchanged omacetaxine was also dominant, together with 4'-DMHHT. In feces very little unchanged omacetaxine was found and the pyrocatechol metabolite of omacetaxine, M534 and 4'-desmethyl homoharringtonine (4'-DMHHT) was the most abundant metabolites. Omacetaxine was extensively metabolized, with subsequent renal and hepatic elimination of the metabolites. The low levels of the metabolites found in plasma indicate that the metabolites are unlikely to contribute materially to the efficacy and/or toxicity of omacetaxine.

  10. Molecular Profiling-Selected Therapy for Treatment of Advanced Pancreaticobiliary Cancer: A Retrospective Multicenter Study

    PubMed Central

    Epelbaum, Ron; Shacham-Shmueli, Einat; Klein, Baruch; Agbarya, Abed; Brenner, Baruch; Brenner, Ronen; Gez, Eliahu; Golan, Talia; Hubert, Ayala; Purim, Ofer; Temper, Mark; Tepper, Ella; Voss, Andreas; Russell, Kenneth; Dvir, Addie; Soussan-Gutman, Lior; Stemmer, Salomon M.; Geva, Ravit

    2015-01-01

    This multicenter cohort study assessed the impact of molecular profiling (MP) on advanced pancreaticobiliary cancer (PBC). The study included 30 patients treated with MP-guided therapy after failing ≥1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS) on MP-guided therapy and the PFS on the last therapy before MP was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit. Overall, ≥1 actionable (i.e., predictive of response to specific therapies) biomarker was identified/patient. Immunohistochemistry (the most commonly used method for guiding treatment decisions) identified 1–6 (median: 4) actionable biomarkers per patient. After MP, patients received 1–4 (median: 1) regimens/patient (most commonly, FOLFIRI/XELIRI). In a decision-impact analysis, of the 27 patients for whom treatment decisions before MP were available, 74.1% experienced a treatment decision change in the first line after MP. Twenty-four patients were evaluable for clinical outcome analysis; in 37.5%, the PFS ratio was ≥1.3. In one-sided exact binomial test versus the null hypothesis, P = 0.0015; therefore, the null hypothesis was rejected. In conclusion, our analysis demonstrated the feasibility, clinical decision impact, and potential clinical benefits of MP-guided therapy in advanced PBC. PMID:26161408

  11. Home Hemodialysis

    MedlinePlus

    ... list clinics that offer home hemodialysis training. Treatment Costs Most health plans pay for home hemodialysis training ... treat. When prepared, this content included the most current information available. For updates or for questions about ...

  12. Home Care

    MedlinePlus

    ... Based Care Nursing Homes Join our e-newsletter! Aging & Health A to Z Home Care Basic Facts & ... March 2013 Posted: March 2012 © 2017 Health in Aging. All rights reserved. Feedback • Site Map • Privacy Policy • ...

  13. Gene expression profile of A549 cells from tissue of 4D model predicts poor prognosis in lung cancer patients.

    PubMed

    Mishra, Dhruva K; Creighton, Chad J; Zhang, Yiqun; Gibbons, Don L; Kurie, Jonathan M; Kim, Min P

    2014-02-15

    The tumor microenvironment plays an important role in regulating cell growth and metastasis. Recently, we developed an ex vivo lung cancer model (four dimensional, 4D) that forms perfusable tumor nodules on a lung matrix that mimics human lung cancer histopathology and protease secretion pattern. We compared the gene expression profile (Human OneArray v5 chip) of A549 cells, a human lung cancer cell line, grown in a petri dish (two-dimensional, 2D), and of the same cells grown in the matrix of our ex vivo model (4D). Furthermore, we obtained gene expression data of A549 cells grown in a petri dish (2D) and matrigel (three-dimensional, 3D) from a previous study and compared the 3D expression profile with that of 4D. Expression array analysis showed 2,954 genes differentially expressed between 2D and 4D. Gene ontology (GO) analysis showed upregulation of several genes associated with extracellular matrix, polarity and cell fate and development. Moreover, expression array analysis of 2D vs. 3D showed 1,006 genes that were most differentially expressed, with only 36 genes (4%) having similar expression patterns as observed between 2D and 4D. Finally, the differential gene expression signature of 4D cells (vs. 2D) correlated significantly with poor survival in patients with lung cancer (n = 1,492), while the expression signature of 3D vs. 2D correlated with better survival in lung cancer patients with lung cancer. As patients with larger tumors have a worse rate of survival, the ex vivo 4D model may be a good mimic of natural progression of tumor growth in lung cancer patients.

  14. Literature Review and Profile of Cancer Diseases Among Afghan Refugees in Iran: Referrals in Six Years of Displacement

    PubMed Central

    Otoukesh, Salman; Mojtahedzadeh, Mona; Figlin, Robert A.; Rosenfelt, Fred P.; Behazin, Arash; Sherzai, Dean; Cooper, Chad J.; Nahleh, Zeina A.

    2015-01-01

    Background There is a paucity of research on the profile of cancers among displaced populations, specifically Afghan refugees in Iran. This study illustrates the pattern of cancers in this population, and highlights the challenges of cancer care in displaced people with the intent that this data will facilitate appropriate allocation of resources to improve care in this population. Material/Methods This was a retrospective cross-sectional study, in which we collected the demographics and profile of cancers among Afghan refugees from 2005 to 2010 from referrals to the United Nations High Commissioner for Refugees (UNHCR) offices in Iran. Accrued evidence by other studies published between January 1993 and July 2014 pertaining to cancer diagnoses in refugees from Afghanistan, Tibet, Syria, Jordan, and Iraq was reviewed. Results Cancer diagnoses accounted for 3083 of 23 152 total referrals, with 49% female and 51% male cases; 23.3% were 0–17 years of age, 61.2% were 18–59, and 15.5% were above 60. The most common health referral for females and males (0–17) was malignant neoplasms of lymphatic and hematopoietic tissue, accounting for 34.2%. In the age groups 18–59 and above 60 for both male and females it was malignant neoplasm of the digestive system, occurring in 26.3% and 48.7%, respectively. Conclusions In the setting of humanitarian crises especially war, cancer diagnoses among refugees is a major health burden both on the host countries and the international community with serious implications considering the recent growing trend in the Middle Eastern countries. The prevalence of certain cancer diagnoses among refugees, like gastrointestinal, respiratory, breast, and genitourinary cancers necessitates a multidirectional approach, primarily aimed at prevention and early detection. International partnerships are essential for improvement in cancer surveillance service availability, and delivery of the standard of care, in an overall effort to reduce the

  15. Regional anesthesia at home

    PubMed Central

    Cheng, Gloria S.; Choy, Lynna P.; Ilfeld, Brian M.

    2009-01-01

    Purpose of review To review the recently published peer-reviewed literature involving regional anesthesia and analgesia in patients at home. Recent findings The potential benefits and risks of regional anesthesia and analgesia at home are pertinent queries, and increased data regarding these topics are rapidly becoming available. Of particular interest is the use of continuous peripheral nerve blocks at home and their potential effect upon hospitalization duration and recovery profile. Summary Advantages of regional techniques include site-specific anesthesia and decreased postoperative opioid use. For shoulder surgeries, the interscalene block provides effective analgesia with minimal complications, whereas the impact and risks of intraarticular injections remain unclear. Perineural catheters are an analgesic option that offer improved pain relief among other benefits. They are now being used at home in both adult and pediatric populations. PMID:18660659

  16. Reach Out to Enhance Wellness in Older Cancer Survivors (RENEW): Design, Methods and Recruitment Challenges of a Home-based Exercise and Diet Intervention to Improve Physical Function among Long-term Survivors of Breast, Prostate, and Colorectal Cancer

    PubMed Central

    Snyder, Denise Clutter; Morey, Miriam C.; Sloane, Richard; Stull, Valeda; Cohen, Harvey Jay; Peterson, Bercedis; Pieper, Carl; Hartman, Terryl J.; Miller, Paige E.; Mitchell, Diane C.; Demark-Wahnefried, Wendy

    2009-01-01

    Objective Cure rates for cancer are increasing, especially for breast, prostate, and colorectal cancer. Despite positive trends in survivorship, a cancer diagnosis can trigger accelerated functional decline that can threaten independence, reduce quality-of-life and increase health care costs, especially among the elderly who comprise the majority of survivors. Lifestyle interventions may hold promise in reorienting functional decline in older cancer survivors, but few studies have been conducted. Method We describe the design and methods of a randomized controlled trial, RENEW (Reach out to ENhancE Wellness), that tests whether a home-based multi-behavior intervention focused on exercise, and including a low-saturated fat, plant-based diet, would improve physical functioning among 641 older, long-term (≥5 years post-diagnosis) survivors of breast, prostate, or colorectal cancer. Challenges to recruitment are examined. Results 20,015 cases were approached, and screened using a two-step screening process to assure eligibility. This population of long-term, elderly cancer survivors had lower rates of response (∼11%) and higher rates of ineligibility (∼70%) than our previous intervention studies conducted on adults with newly diagnosed cancer. Significantly higher response rates were noted among survivors who were white, younger, and more proximal to diagnosis and breast cancer survivors (p-values < 0.001). Conclusions Older cancer survivors represent a vulnerable population for whom lifestyle interventions may hold promise. RENEW may provide guidance in allocating limited resources in order to maximize recruitment efforts aimed at this needy, but hard-to-reach population. PMID:19117329

  17. Effects of Home-Based Diet and Exercise on Functional Outcomes Among Older, Overweight Long-Term Cancer Survivors: The RENEW: Randomized Clinical Trial

    PubMed Central

    Morey, Miriam C.; Snyder, Denise C.; Sloane, Richard; Jay Cohen, Harvey; Peterson, Bercedis; Hartman, Terryl J; Miller, Paige; Mitchell, Diane C.; Demark-Wahnefried, Wendy

    2009-01-01

    Context Five-year survival rates for early-stage colorectal, breast and prostate cancer currently exceed 90% and are increasing. Cancer survivors are at greater risk for second malignancies, other co-morbidities, and accelerated functional decline. Lifestyle interventions may provide benefit, but it is unknown whether long-term cancer survivors can modify their lifestyle behaviors sufficiently to improve functional status. Objective To determine whether a telephone counseling and mailed material-based diet-exercise intervention is effective in reorienting functional decline in older, overweight cancer survivors. Design Randomized controlled trial in which survivors were randomly assigned to intervention (Intervention, n=319) or delayed-intervention control arms (Control, n=322). Setting Home-based from Canada, United Kingdom and 21 United States Participants 641 overweight (body mass index [BMI] ≥ 25), long-term (≥ 5 years) survivors (ages 65–91) of colorectal, breast and prostate cancer recruited July 2005-May 2007. Intervention 12-month home-based tailored program of telephone counseling and mailed materials promoting exercise, improved diet quality, and modest weight loss. Control group wait-listed for 12 months. Main Outcome Measures Change in self-reported physical function (SF-36 physical function subscale: 0–100, high score indicates better function) from baseline to 12 months was the primary endpoint. Secondary outcomes included changes in basic and advanced lower extremity function (0–100), physical activity, BMI, and overall health quality-of-life. Results From an average baseline score of 75.7 to 12-month follow-up, SF-36 function scores declined less rapidly in Intervention [−2.15(95% CI-0.36,−3.93)] versus Control [−4.84(−3.04,−6.63)] arms (p=0.03). Likewise, changes in basic lower extremity function were +0.34(−0.84,1.52) versus −1.89(−0.70,−3.09) from an average baseline score of 78.2, p=0.005. Physical activity, dietary

  18. Multiple Lineages of Human Breast Cancer Stem/Progenitor Cells Identified by Profiling with Stem Cell Markers

    PubMed Central

    Hwang-Verslues, Wendy W.; Kuo, Wen-Hung; Chang, Po-Hao; Pan, Chi-Chun; Wang, Hsing-Hui; Tsai, Sheng-Ta; Jeng, Yung-Ming; Shew, Jin-Yu; Kung, John T.; Chen, Chung-Hsuan; Lee, Eva Y.-H. P.; Chang, King-Jen; Lee, Wen-Hwa

    2009-01-01

    Heterogeneity of cancer stem/progenitor cells that give rise to different forms of cancer has been well demonstrated for leukemia. However, this fundamental concept has yet to be established for solid tumors including breast cancer. In this communication, we analyzed solid tumor cancer stem cell markers in human breast cancer cell lines and primary specimens using flow cytometry. The stem/progenitor cell properties of different marker expressing-cell populations were further assessed by in vitro soft agar colony formation assay and the ability to form tumors in NOD/SCID mice. We found that the expression of stem cell markers varied greatly among breast cancer cell lines. In MDA-MB-231 cells, PROCR and ESA, instead of the widely used breast cancer stem cell markers CD44+/CD24-/low and ALDH, could be used to highly enrich cancer stem/progenitor cell populations which exhibited the ability to self renew and divide asymmetrically. Furthermore, the PROCR+/ESA+ cells expressed epithelial-mesenchymal transition markers. PROCR could also be used to enrich cells with colony forming ability from MB-361 cells. Moreover, consistent with the marker profiling using cell lines, the expression of stem cell markers differed greatly among primary tumors. There was an association between metastasis status and a high prevalence of certain markers including CD44+/CD24−/low, ESA+, CD133+, CXCR4+ and PROCR+ in primary tumor cells. Taken together, these results suggest that similar to leukemia, several stem/progenitor cell-like subpopulations can exist in breast cancer. PMID:20027313

  19. Anticancer drug clustering based on proteomic profiles and a sensitivity database in a lung cancer cell line panel

    PubMed Central

    HINO, MITSUNORI; MATSUDA, KUNIKO; MIYANAGA, AKIHIKO; KURIBAYASI, HIDEHIKO; MIZUTANI, HIDEAKI; NORO, RINTARO; MINEGISHI, YUJI; OKANO, TETSUYA; SEIKE, MASAHIRO; KAWAKAMI, AKIKO; YOSHIMURA, AKINOBU; OGAWA, NAOKI; UESAKA, HARUKA; KUDOH, SHOJI; GEMMA, AKIHIKO

    2010-01-01

    Previously, we performed a molecular pharmacological study that applied a combination of DNA microarray-based gene expression profiling and drug sensitivity tests in vitro with a view to designing an improved chemotherapeutic strategy for advanced lung cancer. Utilizing recent key technological advances in proteomics, particularly antibody array-based methodologies, the current study aimed to examine the benefit of protein expression profiling in an analogous molecular pharmacological context. We performed protein expression analysis in a panel of lung cancer cell lines via an antibody array approach. Using a modified NCI program, we related cell line-specific proteomic profiles to the previously determined cytotoxic activity of a selection of commonly used anticancer agents, namely docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-fluorouracil (5-FU), SN38, cisplatin (CDDP) and carboplatin (CBDCA). In addition, we compared these results with those obtained from our prior DNA microarray-based transcriptomic study. In our expression-drug correlation analysis using antibody array, gemcitabine consistently belonged to an isolated cluster. Docetaxel, paclitaxel, 5-FU, SN38, CBDCA and CDDP were gathered together into one large cluster. These results coincided with those generated by the prior transcriptomic study. Various genes were commonly listed that differentiated gemcitabine from the others. The identified factors associated with drug sensitivities were different between both analyses. Our proteomic profiling data provided confirmation of the previous transcript expression-drug sensitivity correlation analysis. These results suggest that chemotherapy regimens that include gemcitabine should be evaluated in second-line chemotherapy in cases where the first-line chemotherapy did not include this drug. Protein expression-drug sensitivity correlations in lung cancer cells in vitro may provide useful information in determining the most appropriate therapeutic options

  20. Genes overexpressed in different human solid cancers exhibit different tissue-specific expression profiles

    PubMed Central

    Bock Axelsen, Jacob; Lotem, Joseph; Sachs, Leo; Domany, Eytan

    2007-01-01

    We have analyzed gene expression in different normal human tissues and different types of solid cancers derived from these tissues. The cancers analyzed include brain (astrocytoma and glioblastoma), breast, colon, endometrium, kidney, liver, lung, ovary, prostate, skin, and thyroid cancers. Comparing gene expression in each normal tissue to 12 other normal tissues, we identified 4,917 tissue-selective genes that were selectively expressed in different normal tissues. We also identified 2,929 genes that are overexpressed at least 4-fold in the cancers compared with the normal tissue from which these cancers were derived. The overlap between these two gene groups identified 1,340 tissue-selective genes that are overexpressed in cancers. Different types of cancers, including different brain cancers arising from the same lineage, showed differences in the tissue-selective genes they overexpressed. Melanomas overexpressed the highest number of brain-selective genes and this may contribute to melanoma metastasis to the brain. Of all of the genes with tissue-selective expression, those selectively expressed in testis showed the highest frequency of genes that are overexpressed in at least two types of cancer. However, colon and prostate cancers did not overexpress any testis-selective gene. Nearly all of the genes with tissue-selective expression that are overexpressed in cancers showed selective expression in tissues different from the cancers' tissue of origin. Cancers aberrantly expressing such genes may acquire phenotypic alterations that contribute to cancer cell viability, growth, and metastasis. PMID:17664417

  1. Metabolic profiling-based data-mining for an effective chemical combination to induce apoptosis of cancer cells.

    PubMed

    Kumazoe, Motofumi; Fujimura, Yoshinori; Hidaka, Shiori; Kim, Yoonhee; Murayama, Kanako; Takai, Mika; Huang, Yuhui; Yamashita, Shuya; Murata, Motoki; Miura, Daisuke; Wariishi, Hiroyuki; Maeda-Yamamoto, Mari; Tachibana, Hirofumi

    2015-03-31

    Green tea extract (GTE) induces apoptosis of cancer cells without adversely affecting normal cells. Several clinical trials reported that GTE was well tolerated and had potential anti-cancer efficacy. Epigallocatechin-3-O-gallate (EGCG) is the primary compound responsible for the anti-cancer effect of GTE; however, the effect of EGCG alone is limited. To identify GTE compounds capable of potentiating EGCG bioactivity, we performed metabolic profiling of 43 green tea cultivar panels by liquid chromatography-mass spectrometry (LC-MS). Here, we revealed the polyphenol eriodictyol significantly potentiated apoptosis induction by EGCG in vitro and in a mouse tumour model by amplifying EGCG-induced activation of the 67-kDa laminin receptor (67LR)/protein kinase B/endothelial nitric oxide synthase/protein kinase C delta/acid sphingomyelinase signalling pathway. Our results show that metabolic profiling is an effective chemical-mining approach for identifying botanical drugs with therapeutic potential against multiple myeloma. Metabolic profiling-based data mining could be an efficient strategy for screening additional bioactive compounds and identifying effective chemical combinations.

  2. Mutational profiling of brain metastasis from breast cancer: matched pair analysis of targeted sequencing between brain metastasis and primary breast cancer.

    PubMed

    Lee, Ji Yun; Park, Kyunghee; Lim, Sung Hee; Kim, Hae Su; Yoo, Kwai Han; Jung, Ki Sun; Song, Haa-Na; Hong, Mineui; Do, In-Gu; Ahn, TaeJin; Lee, Se Kyung; Bae, Soo Youn; Kim, Seok Won; Lee, Jeong Eon; Nam, Seok Jin; Kim, Duk-Hwan; Jung, Hae Hyun; Kim, Ji-Yeon; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2015-12-22

    Although breast cancer is the second most common cause of brain metastasis with a notable increase of incidence, genes that mediate breast cancer brain metastasis (BCBM) are not fully understood. To study the molecular nature of brain metastasis, we performed gene expression profiling of brain metastasis and matched primary breast cancer (BC). We used the Ion AmpliSeq Cancer Panel v2 covering 2,855 mutations from 50 cancer genes to analyze 18 primary BC and 42 BCBM including 15 matched pairs. The most common BCBM subtypes were triple-negative (42.9%) and basal-like (36.6%). In a total of 42 BCBM samples, 32 (76.2%) harbored at least one mutation (median 1, range 0-7 mutations). Frequently detected somatic mutations included TP53 (59.5%), MLH1 (14.3%), PIK3CA (14.3%), and KIT (7.1%). We compared BCBM with patient-matched primary BC specimens. There were no significant differences in mutation profiles between the two groups. Notably, gene expression in BCBM such as TP53, PIK3CA, KIT, MLH1, and RB1 also seemed to be present in primary breast cancers. The TP53 mutation frequency was higher in BCBM than in primary BC (59.5% vs 38.9%, respectively). In conclusion, we found actionable gene alterations in BCBM that were maintained in primary BC. Further studies with functional testing and a delineation of the role of these genes in specific steps of the metastatic process should lead to a better understanding of the biology of metastasis and its susceptibility to treatment.

  3. Early diffusion of gene expression profiling in breast cancer patients associated with areas of high income inequality.

    PubMed

    Ponce, Ninez A; Ko, Michelle; Liang, Su-Ying; Armstrong, Joanne; Toscano, Michele; Chanfreau-Coffinier, Catherine; Haas, Jennifer S

    2015-04-01

    With the Affordable Care Act reducing coverage disparities, social factors could prominently determine where and for whom innovations first diffuse in health care markets. Gene expression profiling is a potentially cost-effective innovation that guides chemotherapy decisions in early-stage breast cancer, but adoption has been uneven across the United States. Using a sample of commercially insured women, we evaluated whether income inequality in metropolitan areas was associated with receipt of gene expression profiling during its initial diffusion in 2006-07. In areas with high income inequality, gene expression profiling receipt was higher than elsewhere, but it was associated with a 10.6-percentage-point gap between high- and low-income women. In areas with low rates of income inequality, gene expression profiling receipt was lower, with no significant differences by income. Even among insured women, income inequality may indirectly shape diffusion of gene expression profiling, with benefits accruing to the highest-income patients in the most unequal places. Policies reducing gene expression profiling disparities should address low-inequality areas and, in unequal places, practice settings serving low-income patients.

  4. DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker

    PubMed Central

    Esteller, Manel

    2013-01-01

    Using whole blood from 15 twin pairs discordant for breast cancer and high-resolution (450K) DNA methylation analysis, we identified 403 differentially methylated CpG sites including known and novel potential breast cancer genes. Confirming the results in an independent validation cohort of 21 twin pairs determined the docking protein DOK7 as a candidate for blood-based cancer diagnosis. DNA hypermethylation of the promoter region was also seen in primary breast cancer tissues and cancer cell lines. Hypermethylation of DOK7 occurs years before tumor diagnosis, suggesting a role as a powerful epigenetic blood-based biomarker as well as providing insights into breast cancer pathogenesis. PMID:23054610

  5. Application of HPLC combined with laser induced fluorescence for protein profile analysis of tissue homogenates in cervical cancer.

    PubMed

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

    2012-01-01

    A highly objective method, High Performance Liquid Chromatography with Laser Induced Fluorescence (HPLC-LIF) technique was used to study the protein profiles of normal and cervical cancer tissue homogenates. A total of 44 samples including normal cervical biopsy samples from the hysterectomy patients and the patients suffering from different stages of the cervical cancer were recorded by HPLC-LIF and analysed by Principle Component Analysis (PCA) to get statistical information on different tissue components. Discrimination of different stages of the samples was carried out by considering three parameters--scores of factor, spectral residual, and Mahalanobis Distance. Diagnostic accuracy of the method was evaluated using Receiver Operating Characteristic (ROC) analysis, and Youden's index (J) plots. The PCA results showed high sensitivity and specificity (~100) for cervical cancer diagnosis. ROC and Youden's index curves for both normal and malignant standard sets show good diagnostic accuracy with high AUC values. The statistical analysis has shown that the differences in protein profiles can be used to diagnose biochemical changes in the tissue, and thus can be readily applied for the detection of cervical cancer, even in situations where a histopathology examination is not easy because of nonavailability of experienced pathologists.

  6. [Skin cancer: use of preventive measures and demographic profile of a risk group in the city of Botucatu].

    PubMed

    Popim, Regina Célia; Corrente, José Eduardo; Marino, Jaqueline Aparecida Geromel; de Souza, Carolina Arantes

    2008-01-01

    The aim of this paper was to establish the demographic profile of an at-risk group for skin cancer and to assess the preventive measures taken by the studied individuals and by the employer. The methods chosen was a quantitative study with a sample of 33 mail carriers from the Empresa Brasileira de Correios e Telégrafos in Botucatu, Brazil. Information regarding the demographic profile, how long the individual had been working for the company, hours of sun exposure, history of sunburns, family cancer history and skin cancer prevention strategies used by the company was collected by means of a questionnaire. The data were analyzed using Fisher's Exact Test at a 5% probability. The predominant age groups were 26-30 and 31-35 years corresponding to 42,42%. The predominant skin color was white (93,94%) and 81,82% of the studied individuals were working in the company for over five years. 63,63% of the interviewees use sunscreen habitually; those who do not explain this with a lack of habit (in 75% of the cases). As refers to supply of protective equipment by the company, 100% of the subjects answered positively. These findings allow characterizing the studied population as a skin cancer risk group. Prophylactic measures in form of educational actions for awareness building should be adopted and stimulated.

  7. Serum protein profile study of normal and cervical cancer subjects by high performance liquid chromatography with laser-induced fluorescence.

    PubMed

    Sujatha; Rai, Lavanya; Kumar, Pratap; Mahato, Krishna K; Kartha, Vasudevan B; Santhosh, Chidangil

    2008-01-01

    High performance liquid chromatography with high sensitivity laser-induced fluorescence detection is used to study the protein profiles of serum samples from healthy volunteers and cervical cancer subjects. The protein profiles are subjected to principal component analysis (PCA). PCA shows that the large number of chromatograms of a given class of serum samples--say normal/malignant--can be expressed in terms of a small number of factors (principal components). Three parameters--scores of the factors, squared residuals, and Mahalanobis distance--are derived from PCA. The parameters are observed to have a narrow range for protein profiles of standard calibration sets formed from groups of clinically confirmed normal/malignant classes. Limit tests using match/no match of the parameters of any test sample with parameters derived for the standard calibration sets give very good discrimination between malignant and normal samples with high sensitivity (approximately 100%) aand specificity (approximately 94%).

  8. Proteomic Profiling of Exosomes Leads to the Identification of Novel Biomarkers for Prostate Cancer

    SciTech Connect

    Duijvesz, Diederick; Burnum-Johnson, Kristin E.; Gritsenko, Marina A.; Hoogland, Marije; Vredenbregt-van den Berg, Mirella S.; Willemsen, Rob; Luider, Theo N.; Pasa-Tolic, Ljiljana; Jenster, Guido

    2013-12-31

    Introduction: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, biomarker discovery from body fluids is often hampered by the high abundance of many proteins unrelated to disease. An attractive alternative biomarker discovery approach is the isolation of small vesicles (exosomes, ~100 nm). They contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific marker discovery. Profiling prostate cancer-derived exosomes could reveal new markers for this malignancy. Materials and Methods: Exosomes were isolated from 2 immortalized primary prostate epithelial cells (PNT2C2 and RWPE-1) and 2 PCa cell lines (PC346C and VCaP) by ultracentrifugation. Proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS) mode, followed by the Accurate Mass and Time (AMT) tag approach. Exosomal proteins were validated by Western blotting. A Tissue Micro Array, containing 481 different PCa samples (radical prostatectomy), was used to correlate candidate markers with several clinical-pathological parameters such as PSA, Gleason score, biochemical recurrence, and (PCa-related) death. Results: Proteomic characterization resulted in the identification of 263 proteins by at least 2 peptides. Specifically analysis of exosomes from PNT2C2, RWPE-1, PC346C, and VCaP identified 248, 233, 169, and 216 proteins, respectively. Statistical analyses revealed 52 proteins differently expressed between PCa and control cells, 9 of which were more abundant in PCa. Validation by Western blotting confirmed a higher abundance of FASN, XPO1 and PDCD6IP (ALIX) in PCa exosomes. The Tissue Micro 4 Array showed strong correlation of higher Gleason scores and local recurrence with increased cytoplasmic XPO1 (P<0.001). Conclusions: Differentially abundant proteins of cell line-derived exosomes make a clear subdivision between

  9. Prediction of Breast Cancer Metastasis by Gene Expression Profiles: A Comparison of Metagenes and Single Genes

    PubMed Central

    Burton, Mark; Thomassen, Mads; Tan, Qihua; Kruse, Torben A.

    2012-01-01

    Background The popularity of a large number of microarray applications has in cancer research led to the development of predictive or prognostic gene expression profiles. However, the diversity of microarray platforms has made the full validation of such profiles and their related gene lists across studies difficult and, at the level of classification accuracies, rarely validated in multiple independent datasets. Frequently, while the individual genes between such lists may not match, genes with same function are included across such gene lists. Development of such lists does not take into account the fact that genes can be grouped together as metagenes (MGs) based on common characteristics such as pathways, regulation, or genomic location. Such MGs might be used as features in building a predictive model applicable for classifying independent data. It is, therefore, demanding to systematically compare independent validation of gene lists or classifiers based on metagene or individual gene (SG) features. Methods In this study we compared the performance of either metagene-or single gene-based feature sets and classifiers using random forest and two support vector machines for classifier building. The performance within the same dataset, feature set validation performance, and validation performance of entire classifiers in strictly independent datasets were assessed by 10 times repeated 10-fold cross validation, leave-one-out cross validation, and one-fold validation, respectively. To test the significance of the performance difference between MG- and SG-features/classifiers, we used a repeated down-sampled binomial test approach. Results MG- and SG-feature sets are transferable and perform well for training and testing prediction of metastasis outcome in strictly independent data sets, both between different and within similar microarray platforms, while classifiers had a poorer performance when validated in strictly independent datasets. The study showed that MG

  10. Circular RNA and gene expression profiles in gastric cancer based on microarray chip technology.

    PubMed

    Sui, Weiguo; Shi, Zhoufang; Xue, Wen; Ou, Minglin; Zhu, Ying; Chen, Jiejing; Lin, Hua; Liu, Fuhua; Dai, Yong

    2017-03-01

    The aim of the present study was to screen gastric cancer (GC) tissue and adjacent tissue for differences in mRNA and circular (circRNA) expression, to analyze the differences in circRNA and mRNA expression, and to investigate the circRNA expression in gastric carcinoma and its mechanism. circRNA and mRNA differential expression profiles generated using Agilent microarray technology were analyzed in the GC tissues and adjacent tissues. qRT-PCR was used to verify the differential expression of circRNAs and mRNAs according to the interactions between circRNAs and miRNAs as well as the possible existence of miRNA and mRNA interactions. We found that: i) the circRNA expression profile revealed 1,285 significant differences in circRNA expression, with circRNA expression downregulated in 594 samples and upregulated in 691 samples via interactions with miRNAs. The qRT-PCR validation experiments showed that hsa_circRNA_400071, hsa_circRNA_000543 and hsa_circRNA_001959 expression was consistent with the microarray analysis results. ii) 29,112 genes were found in the GC tissues and adjacent tissues, including 5,460 differentially expressed genes. Among them, 2,390 differentially expressed genes were upregulated and 3,070 genes were downregulated. Gene Ontology (GO) analysis of the differentially expressed genes revealed these genes involved in biological process classification, cellular component classification and molecular function classification. Pathway analysis of the differentially expressed genes identified 83 significantly enriched genes, including 28 upregulated genes and 55 downregulated genes. iii) 69 differentially expressed circRNAs were found that might adsorb specific miRNAs to regulate the expression of their target gene mRNAs. The conclusions are: i) differentially expressed circRNAs had corresponding miRNA binding sites. These circRNAs regulated the expression of target genes through interactions with miRNAs and might become new molecular biomarkers for GC

  11. The Evolving Scale and Profile of Cancer Worldwide: Much Ado About Everything.

    PubMed

    Bray, Freddie

    2016-01-01

    Today, cancer is responsible for one in three premature deaths from noncommunicable diseases worldwide, and the number of annual cancer diagnoses will rise to well over 20 million by the year 2030. That cancer is of profound importance to future global health reflects both recent gains in human development as well as mortality transitions that are centuries old. Still, cancer is complex, and the extensive geographical and temporal heterogeneity alerts us to the need for targeted, local approaches to cancer control. The study of trends in specific cancer types remains essential in monitoring and evaluating such strategies and as a descriptive tool for hypothesizing possible contributory factors. Of greatest necessity is an expansion of the availability of high-quality data. To improve the limited cancer incidence data available in low- and middle-income countries (LMIC), the Global Initiative for Cancer Registry Development (http://gicr.iarc.fr) is an international partnership supporting countries to redraw the surveillance map.

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

    DTIC Science & Technology

    2011-10-01

    miRNA genes are located in cancer-associated genomic regions or in fragile sites, frequently amplified or deleted in human cancer, resulting in...the microsatellite one- to four-base DNA repeating units within a tumor 47. Measures of these genetic variations can also be used to identify novel...A, Garlanda C, Mantovani A. Cancer- related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 2009;30:1073

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

    DTIC Science & Technology

    2011-10-01

    of miRNA genes are located in cancer-associated genomic regions or in fragile sites, frequently amplified or deleted in human cancer, resulting in...deletion of the microsatellite one- to four-base DNA repeating units within a tumor 47. Measures of these genetic variations can also be used to identify...Sica A, Garlanda C, Mantovani A. Cancer- related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 2009;30

  14. Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling.

    PubMed

    Chung, Woonbok; Kwabi-Addo, Bernard; Ittmann, Michael; Jelinek, Jaroslav; Shen, Lanlan; Yu, Yinhua; Issa, Jean-Pierre J

    2008-04-30

    DNA hypermethylation is a common epigenetic abnormality in cancer and may serve as a useful marker to clone cancer-related genes as well as a marker of clinical disease activity. To identify CpG islands methylated in prostate cancer, we used methylated CpG island amplification (MCA) coupled with representational difference analysis (RDA) on prostate cancer cell lines. We isolated 34 clones that corresponded to promoter CpG islands, including 5 reported targets of hypermethylation in cancer. We confirmed the data for 17 CpG islands by COBRA and/or pyrosequencing. All 17 genes were methylated in at least 2 cell lines of a 21-cancer cell line panel containing prostate cancer, colon cancer, leukemia, and breast cancer. Based on methylation in primary tumors compared to normal adjacent tissues, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS and NSE1 are candidate biomarkers for prostate cancer (methylation range 50%-85%). The combination of NSE1 or SPOCK2 hypermethylation showed a sensitivity of 80% and specificity of 95% in differentiating cancer from normal. Similarly NKX2-5, SPOCK2, SLC16A12, DPYS and GALR2 are candidate biomarkers for colon cancer (methylation range 60%-95%) and GALR2 hypermethylation showed a sensitivity of 85% and specificity of 95%. Finally, SLC16A12, GALR2, TOX, SPOCK2, EGFR5 and DPYS are candidate biomarkers for breast cancer (methylation range 33%-79%) with the combination of EGFR5 or TOX hypermethylation showing a sensitivity of 92% and specificity of 92%. Expression analysis for eight genes that had the most hypermethylation confirmed the methylation associated silencing and reactivation with 5-aza-2'-deoxycytidine treatment. Our data identify new targets of transcriptional silencing in cancer, and provide new biomarkers that could be useful in screening for prostate cancer and other cancers.

  15. Analysis of gene expression profiles reveals novel correlations with the clinical course of colorectal cancer.

    PubMed

    Cavalieri, Duccio; Dolara, Piero; Mini, Enrico; Luceri, Cristina; Castagnini, Cinzia; Toti, Simona; Maciag, Karolina; De Filippo, Carlotta; Nobili, Stefania; Morganti, Maria; Napoli, Cristina; Tonini, Giulia; Baccini, Michela; Biggeri, Annibale; Tonelli, Francesco; Valanzano, Rosa; Orlando, Claudio; Gelmini, Stefania; Cianchi, Fabio; Messerini, Luca; Luzzatto, Lucio

    2007-01-01

    In order to discover potential markers of prognosis in colorectal cancer (CRC) we have determined gene expression profiles, using cDNA microarrays in CRC samples obtained from 19 patients in Dukes stages C and D, with favorable clinical course (Dukes C patients, survival >5 years after surgery, group A, n=7) or unfavorable clinical course (Dukes stage C and D patients, survival <5 years after surgery, group B, n=12). Gene expression was measured in RNA from each tumor, using a pool of equal amounts of RNA from all tumors as a reference. To identify and rank differentially expressed genes we used three different analytical methods: (i) Significance Analysis of Microarrays (SAM), (ii) Cox's Proportional Hazard Model, and (iii) Trend Filter (a mathematical method for the assessment of numerical trends). The level of expression of a gene in an individual tumor was regarded as of interest when that gene was identified as differentially expressed by at least two of these three methods. By these stringent criteria we identified eight genes (ITGB2, MRPS11, NPR1, TXNL2, PHF10, PRSS8, KCNK3, JAK3) that were correlated with prolonged survival after surgery. Pathway analysis showed that patients with favorable prognosis had several activated metabolic pathways (carbon metabolism, transcription, amino acid and nitrogen metabolism, signaling and fibroblast growth factor receptor pathways). To further validate individual gene expression findings, the RNA level of each gene identified as a marker with microarrays was measured by real-time RT-PCR in CRC samples from an independent group of 55 patients. In this set of patients the Cox Proportional Hazard Model analysis demonstrated a significant association between increased patient survival and low expression of ITGB2 (p = 0.011) and NPR1 (p = 0.023) genes.

  16. Mechanism analysis of colorectal cancer according to the microRNA expression profile

    PubMed Central

    Li, Hong; Zhang, Huichao; Lu, Gang; Li, Qingjing; Gu, Jifeng; Song, Yuan; Gao, Shejun; Ding, Yawen

    2016-01-01

    The present study aimed to identify specific microRNAs (miRs) and their predicted target genes to clarify the molecular mechanisms of colorectal cancer (CRC). An miR expression profile (array ID, GSE39833), which consisted of 88 CRC samples with various tumor-necrosis-metastasis stages and 11 healthy controls, was downloaded from the Gene Expression Omnibus database. Subsequently, the differentially expressed miRs and their target genes were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways of target genes were analyzed using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction (PPI) network of the target genes was constructed using the Search Tool for the Retrieval of Interacting Genes database. The present study identified a total of 18 differentially expressed miRs (upregulated, 8; downregulated, 10) in the sera of the CRC patients compared with the healthy controls. Of these, 3 upregulated (let-7b, miR-1290 and miR-126) and 2 downregulated (miR-16 and miR-760) differentially expressed miRs and their target genes, including cyclin D1 (CCND1), v-myc avian myelocytomatosis viral oncogene homolog (MYC), phosphoinositide-3-kinase, regulatory subunit 2 (beta) (PIK3R2) and SMAD family member 3 (SMAD3), were significantly enriched in the CRC developmental pathway. All these target genes had higher node degrees in the PPI network. In conclusion, let-7b, miR-1290, miR-126, miR-16 and miR-760 and their target genes, CCND1, MYC, PIK3R2 and SMAD3, may be important in the molecular mechanisms for the progression of CRC. PMID:27698796

  17. Culture and Drug Profiling of Patient Derived Malignant Pleural Effusions for Personalized Cancer Medicine

    PubMed Central

    Pietilae, Elina; Vlajnic, Tatjana; Baschiera, Betty; Arabi, Leila; Lorber, Thomas; Oeggerli, Martin; Savic, Spasenija; Obermann, Ellen; Singer, Thomas; Rothschild, Sacha I.; Zippelius, Alfred; Roth, Adrian B.; Bubendorf, Lukas

    2016-01-01

    Introduction The use of patients’ own cancer cells for in vitro selection of the most promising treatment is an attractive concept in personalized medicine. Human carcinoma cells from malignant pleural effusions (MPEs) are suited for this purpose since they have already adapted to the liquid environment in the patient and do not depend on a stromal cell compartment. Aim of this study was to develop a systematic approach for the in-vitro culture of MPEs to analyze the effect of chemotherapeutic as well as targeted drugs. Methods MPEs from patients with solid tumors were selected for this study. After morphological and molecular characterization, they were cultured in medium supplemented with patient-derived sterile-filtered effusion supernatant. Growth characteristics were monitored in real-time using the xCELLigence system. MPEs were treated with a targeted therapeutic (erlotinib) according to the mutational status or chemotherapeutics based on the recommendation of the oncologists. Results We have established a robust system for the ex-vivo culture of MPEs and the application of drug tests in-vitro. The use of an antibody based magnetic cell separation system for epithelial cells before culture allowed treatment of effusions with only moderate tumor cell proportion. Experiments using drugs and drug-combinations revealed dose-dependent and specific growth inhibitory effects of targeted drugs. Conclusions We developed a new approach for the ex-vivo culture of MPEs and the application of drug tests in-vitro using real-time measuring of cell growth, which precisely reproduced the effect of clinically established treatments by standard chemotherapy and targeted drugs. This sets the stage for future studies testing agents against specific targets from genomic profiling of metastatic tumor cells and multiple drug-combinations in a personalized manner. PMID:27548442

  18. The Role of Genomic Profiling in Advanced Breast Cancer: The Two Faces of Janus

    PubMed Central

    Eralp, Yesim

    2016-01-01

    Recent advances in genomic technology have led to considerable improvement in our understanding of the molecular basis that underpins breast cancer biology. Through the use of comprehensive whole genome genomic profiling by next-generation sequencing, an unprecedented bulk of data on driver mutations, key genomic rearrangements, and mechanisms on tumor evolution has been generated. These developments have marked the beginning of a new era in oncology called “personalized or precision medicine.” Elucidation of biologic mechanisms that underpin carcinogenetic potential and metastatic behavior has led to an inevitable explosion in the development of effective targeted agents, many of which have gained approval over the past decade. Despite energetic efforts and the enormous support gained within the oncology community, there are many obstacles in the clinical implementation of precision medicine. Other than the well-known biologic markers, such as ER and Her-2/neu, no proven predictive marker exists to determine the responsiveness to a certain biologic agent. One of the major issues in this regard is teasing driver mutations among the background noise within the bulk of coexisting passenger mutations. Improving bioinformatics tools through electronic models, enhanced by improved insight into pathway dependency may be the step forward to overcome this problem. Next, is the puzzle on spatial and temporal tumoral heterogeneity, which remains to be solved by ultra-deep sequencing and optimizing liquid biopsy techniques. Finally, there are multiple logistical and financial issues that have to be meticulously tackled in order to optimize the use of “precision medicine” in the real-life setting. PMID:27547031

  19. Gene expression profiles in HPV-infected head and neck cancer.

    PubMed

    Schlecht, N F; Burk, R D; Adrien, L; Dunne, A; Kawachi, N; Sarta, C; Chen, Q; Brandwein-Gensler, M; Prystowsky, M B; Childs, G; Smith, R V; Belbin, T J

    2007-11-01

    Epidemiological and laboratory evidence indicate that, in addition to tobacco and alcohol, human papillomaviruses (HPV) play an important aetiological role in a subset of head and neck squamous cell carcinoma (HNSCC). To evaluate the molecular pathogenesis of HPV-infected HNSCC, we compared gene expression patterns between HPV-positive and -negative HNSCC tumours using cDNA microarrays. Tumour tissue was collected from 42 histologically confirmed HNSCC patients from an inner-city area of New York. Total DNA and RNA were extracted and purified from frozen tumour samples and gene expression levels were compared to a universal human reference RNA standard using a 27 323 cDNA microarray chip. HPV detection and genotyping were performed using an MY09/11-PCR system and RT-PCR. HPV was detected in 29% of HNSCC tumours. Most harboured only HPV16 and expressed the HPV16-E6 oncogene. HPV prevalence was highest in pharyngeal tumours (45%). Gene expression patterns that differentiated HPV-positive from negative tumours were compared by supervised classification analysis, and a multiple-gene signature was found to predict HPV16 prevalence in primary HNSCC with a false discovery rate < 0.2. Focusing on never-smokers, we further identified a distinct subset of 123 genes that were specifically dysregulated in HPV16-positive HNSCC. Overexpressed genes in HPV-positive HNSCC tumours included the retinoblastoma-binding protein (p18), replication factor-C gene, and an E2F-dimerization partner transcription factor (TFDP2) that have also been found to be overexpressed in cervical cancer. An additional subset of genes involved in viral defence and immune response, including interleukins and interferon-induced proteins, was found to be down-regulated in HPV-positive tumours, supporting a characteristic and unique transcriptional profile in HPV-induced HNSCC.

  20. RNA profiling reveals familial aggregation of molecular subtypes in non-BRCA1/2 breast cancer families

    PubMed Central

    2014-01-01

    Background In more than 70% of families with a strong history of breast and ovarian cancers, pathogenic mutation in BRCA1 or BRCA2 cannot be identified, even though hereditary factors are expected to be involved. It has been proposed that tumors with similar molecular phenotypes also share similar underlying pathophysiological mechanisms. In the current study, the aim was to investigate if global RNA profiling can be used to identify functional subgroups within breast tumors from families tested negative for BRCA1/2 germline mutations and how these subgroupings relate to different breast cancer patients within the same family. Methods In the current study we analyzed a collection of 70 frozen breast tumor biopsies from a total of 58 families by global RNA profiling and promoter methylation analysis. Results We show that distinct functional subgroupings, similar to the intrinsic molecular breast cancer subtypes, exist among non-BRCA1/2 breast cancers. The distribution of subtypes was markedly different from the distribution found among BRCA1/2 mutation carriers. From 11 breast cancer families, breast tumor biopsies from more than one affected family member were included in the study. Notably, in 8 of these families we found that patients from the same family shared the same tumor subtype, showing a tendency of familial aggregation of tumor subtypes (p-value = 1.7e-3). Using our previously developed BRCA1/2-signatures, we identified 7 non-BRCA1/2 tumors with a BRCA1-like molecular phenotype and provide evidence for epigenetic inactivation of BRCA1 in three of the tumors. In addition, 7 BRCA2-like tumors were found. Conclusions Our finding indicates involvement of hereditary factors in non-BRCA1/2 breast cancer families in which family members may carry genetic susceptibility not just to breast cancer but to a particular subtype of breast cancer. This is the first study to provide a biological link between breast cancers from family members of high-risk non-BRCA1

  1. Technology in MicroRNA Profiling: Circulating MicroRNAs as Noninvasive Cancer Biomarkers in Breast Cancer.

    PubMed

    Pimentel, Fernando; Bonilla, Patricia; Ravishankar, Yashwanth G; Contag, Alec; Gopal, Nimish; LaCour, Sarah; Lee, Trenton; Niemz, Angelika

    2015-10-01

    This report describes technologies to identify and quantify microRNAs (miRNAs) as potential cancer biomarkers, using breast cancer as an example. Most breast cancer patients are not diagnosed until the disease has advanced to later stages, which decreases overall survival rates. Specific miRNAs are up- or downregulated in breast cancer patients at various stages, can be detected in plasma and serum, and have shown promising preliminary clinical sensitivity and specificity for early cancer diagnosis or staging. Nucleic acid testing methods to determine relative concentrations of selected miRNAs include reverse transcription, followed by quantitative PCR (RT-qPCR), microarrays, and next-generation sequencing (NGS). Of these methods, NGS is the most powerful approach for miRNA biomarker discovery, whereas RT-qPCR shows the most promise for eventual clinical diagnostic applications.

  2. Gene Expression Profiling for Guiding Adjuvant Chemotherapy Decisions in Women with Early Breast Cancer

    PubMed Central

    2010-01-01

    Executive Summary In February 2010, the Medical Advisory Secretariat (MAS) began work on evidence-based reviews of published literature surrounding three pharmacogenomic tests. This project came about when Cancer Care Ontario (CCO) asked MAS to provide evidence-based analyses on the effectiveness and cost-effectiveness of three oncology pharmacogenomic tests currently in use in Ontario. Evidence-based analyses have been prepared for each of these technologies. These have been completed in conjunction with internal and external stakeholders, including a Provincial Expert Panel on Pharmacogenomics (PEPP). Within the PEPP, subgroup committees were developed for each disease area. For each technology, an economic analysis was also completed by the Toronto Health Economics and Technology Assessment Collaborative (THETA) and is summarized within the reports. The following reports can be publicly accessed at the MAS website at: www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.html Gene Expression Profiling for Guiding Adjuvant Chemotherapy Decisions in Women with Early Breast Cancer: An Evidence-Based and Economic Analysis Epidermal Growth Factor Receptor Mutation (EGFR) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor (TKI) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer: An Evidence-Based and Ecopnomic Analysis K-RAS testing in Treatment Decisions for Advanced Colorectal Cancer: an Evidence-Based and Economic Analysis Objective To review and synthesize the available evidence regarding the laboratory performance, prognostic value, and predictive value of Oncotype-DX for the target population. Clinical Need: Condition and Target Population The target population of this review is women with newly diagnosed early stage (stage I–IIIa) invasive breast cancer that is estrogen-receptor (ER) positive and/or progesterone-receptor (PR) positive. Much of this review, however, is relevant for women

  3. Discovery and replication of microRNAs for breast cancer risk using genome-wide profiling

    PubMed Central

    Taslim, Cenny; Weng, Daniel Y.; Brasky, Theodore M.; Dumitrescu, Ramona G.; Huang, Kun; Kallakury, Bhaskar V.S.; Krishnan, Shiva; Llanos, Adana A.; Marian, Catalin; McElroy, Joseph; Schneider, Sallie S.; Spear, Scott L.; Troester, Melissa A.; Freudenheim, Jo L.; Geyer, Susan; Shields, Peter G.

    2016-01-01

    Background Genome-wide miRNA expression may be useful for predicting breast cancer risk and/or for the early detection of breast cancer. Results A 41-miRNA model distinguished breast cancer risk in the discovery study (accuracy of 83.3%), which was replicated in the independent study (accuracy = 63.4%, P=0.09). Among the 41 miRNA, 20 miRNAs were detectable in serum, and predicted breast cancer occurrence within 18 months of blood draw (accuracy 53%, P=0.06). These risk-related miRNAs were enriched for HER-2 and estrogen-dependent breast cancer signaling. Materials and Methods MiRNAs were assessed in two cross-sectional studies of women without breast cancer and a nested case-control study of breast cancer. Using breast tissues, a multivariate analysis was used to model women with high and low breast cancer risk (based upon Gail risk model) in a discovery study of women without breast cancer (n=90), and applied to an independent replication study (n=71). The model was then assessed using serum samples from the nested case-control study (n=410). Conclusions Studying breast tissues of women without breast cancer revealed miRNAs correlated with breast cancer risk, which were then found to be altered in the serum of women who later developed breast cancer. These results serve as proof-of-principle that miRNAs in women without breast cancer may be useful for predicting breast cancer risk and/or as an adjunct for breast cancer early detection. The miRNAs identified herein may be involved in breast carcinogenic pathways because they were first identified in the breast tissues of healthy women. PMID:27833082

  4. Characterization of the glycosylation profile of the human breast cancer cell line, MDA-231, and a bone colonizing variant.

    PubMed

    Carcel-Trullols, Jaime; Stanley, Joseph S; Saha, Rinku; Shaaf, Saeid; Bendre, Manali S; Monzavi-Karbassi, Behjatolah; Suva, Larry J; Kieber-Emmons, Thomas

    2006-05-01

    The mechanisms that guide organ-specific metastases are not fully established. The aberrant expression of carbohydrates may play a fundamental role in defining the molecular mechanisms for metastases to distant organs and facilitate positive interactions within the target organ. The purpose of the present study was to determine the glycomic profile of a variant of the MDA-MB-231 breast cancer cell line that colonizes the bone and to ascribe mechanistic functions mediated by carbohydrates that might correlate with clinical bone metastases. The carbohydrate expression profiles of osteolytic MDA-MET breast cancer cells and non-osteolytic parental MDA-MB-231 cells were determined. MDA-MET cells were derived from MDA-MB-231 cells by in vivo selection of metastatic bone lesions following intracardiac inoculation. The two related breast cancer cell lines expressed distinct carbohydrate profiles; MDA-MET cells displayed an increased expression of alpha (2,6) linked sialic acid, N-beta1-6 GlcNAc, and sialylated Lewis-A antigen, and decreased expression of Galbeta1,3GalNAc as detected using a combination of lectins and anti-carbohydrate antibodies. Microarray analysis demonstrated an increased expression of glycosyltransferase genes, correlative for the distinct glycomic phenotype. The altered glycomic phenotypes of MDA-MET cells include effects on the differential binding to bone marrow endothelial cells, enhanced ECM binding and an increase in invasive potential. These data suggest that the glycomic phenotype of MDA-MET cells is associated with a select set of accumulated functions that collectively impact on the bone metastases and bone colonization capacity of breast cancer cells.

  5. Bioenergetic analysis of ovarian cancer cell lines: profiling of histological subtypes and identification of a mitochondria-defective cell line.

    PubMed

    Dier, Usawadee; Shin, Dong-Hui; Hemachandra, L P Madhubhani P; Uusitalo, Larissa M; Hempel, Nadine

    2014-01-01

    Epithelial ovarian cancer (EOC) is the most lethal of all gynecological cancers, and encompasses distinct histological subtypes that have specific genetic and tissues-of-origin differences. Ovarian clear cell carcinoma (OCCC) represents approximately 10% of cases and has been termed a stress responsive cancer. OCCC is characterized by increased expression of oxidative stress and glycolysis-related genes. In the present study, we hypothesized that bioenergetic profiling might uniquely distinguish OCCC from other EOC histological subtypes. Using an extracellular flux analyzer, OCCC lines (ES-2, TOV-21-G) were shown to be highly metabolically active, with high oxygen consumption rate (OCR) and high extracellular acidification rate (ECAR), indicative of enhanced mitochondrial oxidative phosphorylation and glycolytic rate, respectively. A high bioenergetics profile was associated with the cell lines' ability to form anchorage independent spheroids. Given their high glycolytic and mitochondrial activity, OCCC cells displayed strong sensitivity to 2-deoxy-D-glucose and Rotenone growth inhibition, although this chemosensitivity profile was not specific to only OCCC cells. Bioenergetic profiling also identified a non-OCCC cell line, OVCA420, to have severely compromised mitochondrial function, based on low OCR and a lack of stimulation of maximal respiration following application of the uncoupler FCCP. This was accompanied by mitochondrial morphology changes indicative of enhanced fission, increased expression of the mitochondrial fission protein Drp1, a loss of mitochondrial membrane potential and dependence on glycolysis. Importantly, this loss of mitochondrial function was accompanied by the inability of OVCA420 cells to cope with hypoxic stress, and a compromised ability to stabilize HIF-1α in response to 1% O2 hypoxia. This knowledge may be imperative for researchers planning to utilize this cell line for further studies of metabolism and hypoxia, and suggests that

  6. Using Expression Profiling to Understand the Effects of Chronic Cadmium Exposure on MCF-7 Breast Cancer Cells

    PubMed Central

    Lubovac-Pilav, Zelmina; Borràs, Daniel M.; Ponce, Esmeralda; Louie, Maggie C.

    2013-01-01

    Cadmium is a metalloestrogen known to activate the estrogen receptor and promote breast cancer cell growth. Previous studies have implicated cadmium in the development of more malignant tumors; however the molecular mechanisms behind this cadmium-induced malignancy remain elusive. Using clonal cell lines derived from exposing breast cancer cells to cadmium for over 6 months (MCF-7-Cd4, -Cd6, -Cd7, -Cd8 and -Cd12), this study aims to identify gene expression signatures associated with chronic cadmium exposure. Our results demonstrate that prolonged cadmium exposure does not merely result in the deregulation of genes but actually leads to a distinctive expression profile. The genes deregulated in cadmium-exposed cells are involved in multiple biological processes (i.e. cell growth, apoptosis, etc.) and molecular functions (i.e. cadmium/metal ion binding, transcription factor activity, etc.). Hierarchical clustering demonstrates that the five clonal cadmium cell lines share a common gene expression signature of breast cancer associated genes, clearly differentiating control cells from cadmium exposed cells. The results presented in this study offer insights into the cellular and molecular impacts of cadmium on breast cancer and emphasize the importance of studying chronic cadmium exposure as one possible mechanism of promoting breast cancer progression. PMID:24376830

  7. Transcript profiling identifies novel key players mediating the growth inhibitory effect of NS-398 on human pancreatic cancer cells.

    PubMed

    Youns, Mahmoud; Efferth, Thomas; Hoheisel, Jörg D

    2011-01-10

    Pancreatic cancer is one of the most aggressive human malignancies with an increasing incidence worldwide. Despite an increase in the number of systemic treatments available for pancreatic cancer, the impact of therapy on the clinical course of the disease has been modest, underscoring an urgent need for new therapeutic options. Although selective cyclooxygenase-2 inhibitors have been demonstrated to have cancer-preventive effects, the mechanism of their effects is not clearly known. Moreover, there have been no unbiased studies to identify novel molecular targets of NS-398 regarding pancreatic cancer. Here we undertook a gene expression profiling study to identify novel molecular targets modulating the growth inhibitory effects of NS-398 on pancreatic cancer cell lines. Our mRNA-based gene expression results showed that the growth inhibitory effect of NS-398 was accompanied with an activation of G1/S and G2/M cell cycle regulation, P53 signalling, apoptotic, aryl hydrocarbon receptor and death receptor signalling pathways. Moreover, we reported, for the first time, that the growth inhibitory effect of NS-398 is mediated by down-regulation of RRM2, CTGF, MCM2 and PCNA and up-regulation of NAG-1 in all cell lines.

  8. Inferring alterations in cell-to-cell communication in HER2+ breast cancer using secretome profiling of three cell models

    PubMed Central

    Klinke, David J.; Kulkarni, Yogesh M.; Wu, Yueting; Byrne-Hoffman, Christina

    2015-01-01

    Challenges in demonstrating durable clinical responses to molecular-targeted therapies has sparked a re-emergence in viewing cancer as an evolutionary process. In somatic evolution, cellular variants are introduced through a random process of somatic mutation and are selected for improved fitness through a competition for survival. In contrast to Darwinian evolution, cellular variants that are retained may directly alter the fitness competition. If cell-to-cell communication is important for selection, the biochemical cues secreted by malignant cells that emerge should be altered to bias this fitness competition. To test this hypothesis, we compared the proteins secreted in vitro by two human HER2+ breast cancer cell lines (BT474 and SKBR3) relative to a normal human mammary epithelial cell line (184A1) using a proteomics workflow that leveraged two-dimensional gel electrophoresis (2DE) and MALDI-TOF mass spectrometry. Supported by the 2DE secretome maps and identified proteins, the two breast cancer cell lines exhibited secretome profiles that were similar to each other and, yet, were distinct from the 184A1 secretome. Using protein-protein interaction and pathway inference tools for functional annotation, the results suggest that all three cell lines secrete exosomes, as confirmed by scanning electron microscopy. Interestingly, the HER2+ breast cancer cell line exosomes are enriched in proteins involved in antigen processing and presentation and glycolytic metabolism. These pathways are associated with two of the emerging hallmarks of cancer: evasion of tumor immunosurveillance and deregulating cellular energetics. PMID:24752654

  9. [Risk profiling in cancer surveillance in contaminated sites: an example from the ISS-AIRTUM collaborative study].

    PubMed

    Catelan, Dolores; Buzzoni, Carlotta; Coviello, Enzo; Crocetti, Emanuele; Pasetto, Roberto; Pirastu, Roberta; Biggeri, Annibale

    2014-01-01

    Epidemiological surveillance on high risk environmental areas or areas covered by cancer registration yields long inventories of relative risks. Summaries of the results' tables must be produced to identify priorities and tailor public health actions. The aim is, therefore, to draw conclusions from each area's disease profile, or from the area signature of each disease.With this inmind, we used data on cancer incidence from 17 Cancer Registries that participated in the ISS-AIRTUM (National Institute of Health-Italian Network of Cancer Registries) study, and we produced conditional and marginal rankings of areas/diseases using a multivariate hierarchical Bayesian model. In this context, it is important to obtain an uncertainty evaluation by calculating the credibility intervals of ranks. The areas marginal ranking shows a large overlapping of credibility intervals, such that it is not possible to speak of a limited number of ISS-AIRTUM areas as being particularly affected. Every ISS-AIRTUMarea, therefore,must be considered individually and ordering themby ranking of cancer incidence wouldn't be appropriate. Instead,marginal ranking of diseases highlights the impact of asbestos exposure in all the analyzed areas.

  10. Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer

    PubMed Central

    Di, Li-Jun; Byun, Jung S.; Wong, Madeline M.; Wakano, Clay; Taylor, Tara; Bilke, Sven; Baek, Songjoon; Hunter, Kent; Yang, Howard; Lee, Maxwell; Zvosec, Celia; Khramtsova, Galina; Cheng, Fan; Perou, Charles M.; Miller, C. Ryan; Raab, Rachel; Olopade, Olufunmilayo I.; Gardner, Kevin

    2013-01-01

    The C-terminal binding protein (CtBP) is a NADH-dependent transcriptional repressor that links carbohydrate metabolism to epigenetic regulation by recruiting diverse histone modifying complexes to chromatin. Here, global profiling of CtBP in breast cancer cells reveals that it drives epithelial to mesenchymal transition, stem cell pathways, and genome instability. CtBP expression induces mesenchymal and stem cell-like features while CtBP depletion or caloric restriction reverses gene repression and increases DNA repair. Multiple members of the CtBP-targeted gene network are selectively down-regulated in aggressive breast cancer subtypes. Differential expression of CtBP-targeted genes predicts poor clinical outcome in breast cancer patients, and elevated levels of CtBP in patient tumors predict shorter median survival. Finally, both CtBP promoter targeting and gene repression can be reversed by small molecule inhibition. These findings define broad roles for CtBP in breast cancer biology and suggest novel chromatin-based strategies for pharmacologic and metabolic intervention in cancer. PMID:23385593

  11. Integrative bioinformatic analyses of an oncogenomic profile reveal the biology of endometrial cancer and guide drug discovery.

    PubMed

    Wong, Henry Sung-Ching; Juan, Yung-Shun; Wu, Mei-Shin; Zhang, Yan-Feng; Hsu, Yu-Wen; Chen, Huang-Hui; Liu, Wei-Min; Chang, Wei-Chiao

    2016-02-02

    A major challenge in personalized cancer medicine is to establish a systematic approach to translate huge oncogenomic datasets to clinical situations and facilitate drug discovery for cancers such as endometrial carcinoma. We performed a genome-wide somatic mutation-expression association study in a total of 219 endometrial cancer patients from TCGA database, by evaluating the correlation between ~5,800 somatic mutations to ~13,500 gene expression levels (in total, ~78, 500, 000 pairs). A bioinformatics pipeline was devised to identify expression-associated single nucleotide variations (eSNVs) which are crucial for endometrial cancer progression and patient prognoses. We further prioritized 394 biologically risky mutational candidates which mapped to 275 gene loci and demonstrated that these genes collaborated with expression features were significantly enriched in targets of drugs approved for solid tumors, suggesting the plausibility of drug repurposing. Taken together, we integrated a fundamental endometrial cancer genomic profile into clinical circumstances, further shedding light for clinical implementation of genomic-based therapies and guidance for drug discovery.

  12. Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools.

    PubMed

    Canturk, Kemal Murat; Ozdemir, Muhsin; Can, Cavit; Öner, Setenay; Emre, Ramazan; Aslan, Huseyin; Cilingir, Oguz; Ciftci, Evrim; Celayir, Fatih Mehmet; Aldemir, Ozgur; Özen, Mustafa; Artan, Sevilhan

    2014-12-01

    Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs' regulatory networks. In this study, we aimed to construct potential networks of bladder-cancer-related miRNAs and their known target genes using miRNA expression profiling and bioinformatics tools and to investigate potential key molecules that might play roles in bladder cancer regulatory networks. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation using two randomly selected miRNAs. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of three selected KEGG pathways were visualized by Cytoscape software. We finally gained 19 deregulated miRNAs, including 5 ups- and 14 down regulated in 27 bladder-cancer tissue samples and 8 normal urothelial tissue samples. The enrichment results of deregulated miRNAs and known target genes showed that most pathways were related to cancer or cell signaling pathways. We determined the hub CDK6, BCL2, E2F3, PTEN, MYC, RB, and ERBB3 target genes and hub hsa-let-7c, hsa-miR-195-5p, hsa-miR-141-3p, hsa-miR-26a-5p, hsa-miR-23b-3p, and hsa-miR-125b-5p miRNAs of the constructed networks. These findings provide new insights into the bladder cancer regulatory networks and give us a hypothesis that hsa-let-7c, hsa-miR-195-5p, and hsa-miR-125b-5p, along with CDK4 and CDK6 genes might exist in the same bladder cancer pathway. Particularly, hub miRNAs and genes might be potential biomarkers for bladder cancer clinics.

  13. Home front.

    PubMed

    2001-04-04

    Ninety-year-old Ivy Tabberer protested against the closure of her care home at the Houses of Parliament last week. She was joined by fellow residents in the Havering Action Against Home Closures group and three generations of her family. Ms Tabberer is pictured with daughter Doreen Walpole (left), granddaughter Annette (far right) and great granddaughter Shereen (middle). 'If all the homes close,' said Ms Tabberer, 'where are we going to stay?'

  14. Anemia profiles in patients with lung cancer: what have we learned from the European Cancer Anaemia Survey (ECAS)?

    PubMed

    Kosmidis, Paris; Krzakowski, Maciej

    2005-12-01

    The often-aggressive therapy, including platinum-based regimens, required to treat lung cancer patients results in a significant risk for anemia in this population. Results of the recent European Cancer Anaemia Survey (ECAS) showed that, at enrollment, 37.6% (753/2002) of lung cancer patients were anemic; rates by cancer treatment were 50.0% on concomitant chemotherapy/radiotherapy, 39.0% on chemotherapy, 31.7% on radiotherapy, 38.6% on combination treatment, and 30.7%, on no treatment. At enrollment, of 605 patients receiving platinum therapy, 50.1% were anemic versus 30.6% of 1252 receiving nonplatinum regimens. During ECAS, 83.3% of lung cancer patients who received chemotherapy were anemic at some time, with the prevalence of anemia in platinum-treated patients increasing progressively from 23.5% at Cycle 1 to 77.3% at Cycle 6 (corresponding values for nonplatinum-treated patients, 32.9% and 57.7%). However, only 47% of anemic patients received anemia treatment, which, when provided, often was not initiated until hemoglobin (Hb) levels were relatively low (initiation Hb: epoetin, 9.1 g/dL; transfusion, 8.5 g/dL). Logistical analysis of ECAS data identified treatment with platinum, female sex, and initial Hb level as risk factors for anemia in lung cancer patients. Given the potential adverse consequences of anemia in lung cancer patients, including diminished quality of life (QOL), it is advisable that treatment patterns for anemia management, especially in regard to anemia monitoring and Hb level used to initiate treatment, be reviewed and optimized, with the goal of optimizing overall patient care. Also, anemia risk factors should be considered, which may help clinicians identify lung cancer patients particularly at risk for this problem, allowing the planning and initiation of appropriate treatment for effective and timely anemia management, thus preserving patient QOL.

  15. Treatment of patients with refractory metastatic cancer according to molecular profiling on tumor tissue in the clinical routine: an interim-analysis of the ONCO-T-PROFILE project

    PubMed Central

    Seeber, Andreas; Gastl, Guenther; Ensinger, Christian; Spizzo, Gilbert; Willenbacher, Wolfgang; Kocher, Florian; Leitner, Christoph; Willenbacher, Ella; Amann, Arno; Steiner, Normann; Eisterer, Wolfgang; Voss, Andreas; Russell, Kenneth; Zwierzina, Heinz

    2016-01-01

    Introduction Patients with refractory metastatic cancer have been shown to benefit from molecular profiling of tumor tissue. The ONCO-T-PROFILE project was launched in March 2014 at the Innsbruck Medical University. Within 2 years our project aims to recruit 110 patients with stage IV cancer refractory to standard therapy. Our data presented here are based on an interim-analysis. Methods Tumor tissue specimens were submitted for molecular profiling to the certified laboratory (Caris Life Science, USA). Druggable tumor targets were selected based on biomarker status to agents with potential clinical benefit. Clinical benefit was defined as a PFS ratio (=PFS upon treatment according to the molecular profile/ PFS upon the last prior therapy) ≥ 1.3. Results As of April 2015, tumors from 50 patients have been molecularly profiled and one or more targets were detectable in 48 specimens (98%). So far, 19 (38%) patients have been treated according to their molecular tumor profile. To date, 8 (42%) patients have reached a PFS ratio of ≥ 1.3. Conclusions We could show that molecular profiling is feasible in the clinical routine. A proportion of patients might benefit from an individualized treatment approach based on molecular profiling. As a result, we will proceed to enroll patients in ONCO-T-PROFILE. PMID:28050231

  16. Genome-wide gene expression profiling suggests distinct radiation susceptibilities in sporadic and post-Chernobyl papillary thyroid cancers

    PubMed Central

    Detours, V; Delys, L; Libert, F; Weiss Solís, D; Bogdanova, T; Dumont, J E; Franc, B; Thomas, G; Maenhaut, C

    2007-01-01

    Papillary thyroid cancers (PTCs) incidence dramatically increased in the vicinity of Chernobyl. The cancer-initiating role of radiation elsewhere is debated. Therefore, we searched for a signature distinguishing radio-induced from sporadic cancers. Using microarrays, we compared the expression profiles of PTCs from the Chernobyl Tissue Bank (CTB, n=12) and from French patients with no history of exposure to ionising radiations (n=14). We also compared the transcriptional responses of human lymphocytes to the presumed aetiological agents initiating these tumours, γ-radiation and H2O2. On a global scale, the transcriptomes of CTB and French tumours are indistinguishable, and the transcriptional responses to γ-radiation and H2O2 are similar. On a finer scale, a 118 genes signature discriminated the γ-radiation and H2O2 responses. This signature could be used to classify the tumours as CTB or French with an error of 15–27%. Similar results were obtained with an independent signature of 13 genes involved in homologous recombination. Although sporadic and radio-induced PTCs represent the same disease, they are distinguishable with molecular signatures reflecting specific responses to γ-radiation and H2O2. These signatures in PTCs could reflect the susceptibility profiles of the patients, suggesting the feasibility of a radiation susceptibility test. PMID:17712314

  17. Extensive surface protein profiles of extracellular vesicles from cancer cells may provide diagnostic signatures from blood samples

    PubMed Central

    Belov, Larissa; Matic, Kieran J.; Hallal, Susannah; Best, O. Giles; Mulligan, Stephen P.; Christopherson, Richard I.

    2016-01-01

    Extracellular vesicles (EV) are membranous particles (30–1,000 nm in diameter) secreted by cells. Important biological functions have been attributed to 2 subsets of EV, the exosomes (bud from endosomal membranes) and the microvesicles (MV; bud from plasma membranes). Since both types of particles contain surface proteins derived from their cell of origin, their detection in blood may enable diagnosis and prognosis of disease. We have used an antibody microarray (DotScan) to compare the surface protein profiles of live cancer cells with those of their EV, based on their binding patterns to immobilized antibodies. Initially, EV derived from the cancer cell lines, LIM1215 (colorectal cancer) and MEC1 (B-cell chronic lymphocytic leukaemia; CLL), were used for assay optimization. Biotinylated antibodies specific for EpCAM (CD326) and CD19, respectively, were used to detect captured particles by enhanced chemiluminescence. Subsequently, this approach was used to profile CD19+ EV from the plasma of CLL patients. These EV expressed a subset (~40%) of the proteins detected on CLL cells from the same patients: moderate or high levels of CD5, CD19, CD31, CD44, CD55, CD62L, CD82, HLA-A,B,C, HLA-DR; low levels of CD21, CD49c, CD63. None of these proteins was detected on EV from the plasma of age- and gender-matched healthy individuals. PMID:27086589

  18. Comprehensive gene and microRNA expression profiling reveals miR-206 inhibits MET in lung cancer metastasis.

    PubMed

    Chen, Qing-yong; Jiao, De-min; Yan, Li; Wu, Yu-quan; Hu, Hui-zhen; Song, Jia; Yan, Jie; Wu, Li-jun; Xu, Li-qun; Shi, Jian-guo

    2015-08-01

    MiRNAs associated with the metastasis of lung cancer remain largely unexplored. In this study, gene and miRNA expression profiling were performed to analyze the global expression of mRNAs and miRNAs in human high- and low-metastatic lung cancer cell strains. By developing an integrated bioinformatics analysis, six miRNAs (miR-424-3p, miR-450b-5p, miR-335-5p, miR-34a-5p, miR-302b-3p and miR-206) showed higher target gene degrees in the miRNA-gene network and might be potential metastasis-related miRNAs. Using the qRT-PCR method, the six miRNAs were further confirmed to show a significant expression difference between human lung cancer and normal tissue samples. Since miR-206 showed lower expression both in lung cancer tissues and cell lines, it was used as an example for further functional verification. The wound healing assay and transwell invasion assay showed that miR-206 mimics significantly inhibited the cell migration and invasion of the high-metastatic lung cancer 95D cell strain. One of its predicted targets in our miRNA-gene network, MET, was also obviously decreased at the protein level when miR-206 was overexpressed. Instead, miR-206 inhibitors increased MET protein expression, cell migration and invasion of the low-metastatic lung cancer 95C cell strain. Meanwhile, the luciferase assay showed that MET was a direct target of miR-206. Furthermore, MET gene silence showed a similar anti-migration and anti-invasion effect with miR-206 mimics in 95D cells and could partially attenuate the migration- and invasion-promoting effect of miR-206 inhibitors in 95C cells, suggesting that miR-206 targets MET in lung cancer metastasis. Finally, we also demonstrated that miR-206 can significantly inhibit lung cancer proliferation and metastasis in mouse models. In conclusion, our study provided a miRNA-gene regulatory network in lung cancer metastasis and further demonstrated the roles of miR-206 and MET in this process, which enhances the understanding of the

  19. Candidate Luminal B Breast Cancer Genes Identified by Genome, Gene Expression and DNA Methylation Profiling

    PubMed Central

    Addou-Klouche, Lynda; Finetti, Pascal; Saade, Marie-Rose; Manai, Marwa; Carbuccia, Nadine; Bekhouche, Ismahane; Letessier, Anne; Charafe-Jauffret, Emmanuelle; Jacquemier, Jocelyne; Spicuglia, Salvatore; de The, Hugues; Viens, Patrice; Bertucci, François; Birnbaum, Daniel; Chaffanet, Max

    2014-01-01

    Breast cancers (BCs) of the luminal B subtype are estrogen receptor-positive (ER+), highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs), DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs) presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15) and UTRN (6q24), were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype. PMID:24416132

  20. Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling.

    PubMed

    Cornen, Stéphanie; Guille, Arnaud; Adélaïde, José; Addou-Klouche, Lynda; Finetti, Pascal; Saade, Marie-Rose; Manai, Marwa; Carbuccia, Nadine; Bekhouche, Ismahane; Letessier, Anne; Raynaud, Stéphane; Charafe-Jauffret, Emmanuelle; Jacquemier, Jocelyne; Spicuglia, Salvatore; de The, Hugues; Viens, Patrice; Bertucci, François; Birnbaum, Daniel; Chaffanet, Max

    2014-01-01

    Breast cancers (BCs) of the luminal B subtype are estrogen receptor-positive (ER+), highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs), DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs) presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15) and UTRN (6q24), were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype.

  1. Genomic profiling of stage II and III colon cancers reveals APC mutations to be associated with survival in stage III colon cancer patients

    PubMed Central

    van den Broek, Evert; Krijgsman, Oscar; Sie, Daoud; Tijssen, Marianne; Mongera, Sandra; van de Wiel, Mark A.; Th. Belt, Eric J.; den Uil, Sjoerd H.; Bril, Herman; Stockmann, Hein B.A.C.; Ylstra, Bauke; Carvalho, Beatriz; Meijer, Gerrit A.; Fijneman, Remond J.A.

    2016-01-01

    Tumor profiling of DNA alterations, i.e. gene point mutations, somatic copy number aberrations (CNAs) and structural variants (SVs), improves insight into the molecular pathology of cancer and clinical outcome. Here, associations between genomic aberrations and disease recurrence in stage II and III colon cancers were investigated. A series of 114 stage II and III microsatellite stable colon cancer samples were analyzed by high-resolution array-comparative genomic hybridization (array-CGH) to detect CNAs and CNA-associated chromosomal breakpoints (SVs). For 60 of these samples mutation status of APC, TP53, KRAS, PIK3CA, FBXW7, SMAD4, BRAF and NRAS was determined using targeted massive parallel sequencing. Loss of chromosome 18q12.1-18q12.2 occurred more frequently in tumors that relapsed than in relapse-free tumors (p < 0.001; FDR = 0.13). In total, 267 genes were recurrently affected by SVs (FDR < 0.1). CNAs and SVs were not associated with disease-free survival (DFS). Mutations in APC and TP53 were associated with increased CNAs. APC mutations were associated with poor prognosis in (5-fluorouracil treated) stage III colon cancers (p = 0.005; HR = 4.1), an effect that was further enhanced by mutations in MAPK pathway (KRAS, NRAS, BRAF) genes. We conclude that among multiple genomic alterations in CRC, strongest associations with clinical outcome were observed for common mutations in APC. PMID:27729614

  2. Uterine Cancer Statistics

    MedlinePlus

    ... Research AMIGAS Fighting Cervical Cancer Worldwide Stay Informed Statistics for Other Kinds of Cancer Breast Cervical Colorectal ( ... Skin Vaginal and Vulvar Cancer Home Uterine Cancer Statistics Language: English Español (Spanish) Recommend on Facebook Tweet ...

  3. Biomarker discovery to improve prediction of breast cancer survival: using gene expression profiling, meta-analysis, and tissue validation

    PubMed Central

    Meng, Liwei; Xu, Yingchun; Xu, Chaoyang; Zhang, Wei

    2016-01-01

    Purpose Breast cancer is the leading cause of cancer death worldwide in women. The molecular mechanism for human breast cancer is unknown. Gene microarray has been widely used in breast cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis survival. So far, the valuable multigene signatures in clinical practice are unclear, and the biological importance of individual genes is difficult to detect, as the described signatures virtually do not overlap. Early prognosis of this disease, breast invasive ductal carcinoma (IDC) and breast ductal carcinoma in situ (DCIS), is vital in breast surgery. Methods Thus, this study reports gene expression profiling in large breast cancer cohorts from Gene Expression Omnibus, including GSE29044 (N=138) and GSE10780 (N=185) test series and four independent validation series GSE21653 (N=266), GSE20685 (N=327), GSE26971 (N=276), and GSE12776 (N=204). Significantly differentially expressed genes in human breast IDC and breast DCIS were detected by transcriptome microarray analysis. Results We created a set of three genes (MAMDC2, TSHZ2, and CLDN11) that were significantly correlated with disease-free survival of breast cancer patients using a univariate Cox regression model (significance level P<0.01) in a meta-analysis. Based on the risk score of the three genes, the test series patients could be separated into low-risk and high-risk groups with significantly different survival times. This signature was validated in the other three cohorts. The prognostic value of this three-gene signature was confirmed in the internal validation series and another four independent breast cancer data sets. The prognostic impact of one of the three genes, CLDN11, was confirmed by immunohistochemistry. CLDN11 was significantly overexpressed in human breast IDC as compared with normal breast tissues and breast DCIS. Conclusion Using novel gene expression profiling together with a meta-analysis validation

  4. Prediction of Breast Cancer Risk Based on Profiling With Common Genetic Variants

    PubMed Central

    Pharoah, Paul D. P.; Michailidou, Kyriaki; Tyrer, Jonathan; Brook, Mark N.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Brown, Judith; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Peto, Julian; dos-Santos-Silva, Isabel; Dudbridge, Frank; Johnson, Nichola; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Rutgers, Emiel J.; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Figueroa, Jonine; Chanock, Stephen J.; Brinton, Louise; Lissowska, Jolanta; Couch, Fergus J.; Olson, Janet E.; Vachon, Celine; Pankratz, Vernon S.; Lambrechts, Diether; Wildiers, Hans; Van Ongeval, Chantal; van Limbergen, Erik; Kristensen, Vessela; Grenaker Alnæs, Grethe; Nord, Silje; Borresen-Dale, Anne-Lise; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fasching, Peter A.; Haeberle, Lothar; Ekici, Arif B.; Beckmann, Matthias W.; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Trentham-Dietz, Amy; Newcomb, Polly; Titus, Linda; Egan, Kathleen M.; Hunter, David J.; Lindstrom, Sara; Tamimi, Rulla M.; Kraft, Peter; Rahman, Nazneen; Turnbull, Clare; Renwick, Anthony; Seal, Sheila; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Benitez, Javier; Pilar Zamora, M.; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Dörk, Thilo; Anton-Culver, Hoda; Neuhausen, Susan L.; Ziogas, Argyrios; Bernstein, Leslie; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; van Asperen, Christi J.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Khusnutdinova, Elza; Bermisheva, Marina; Prokofyeva, Darya; Takhirova, Zalina; Meindl, Alfons; Schmutzler, Rita K.; Sutter, Christian; Yang, Rongxi; Schürmann, Peter; Bremer, Michael; Christiansen, Hans; Park-Simon, Tjoung-Won; Hillemanns, Peter; Guénel, Pascal; Truong, Thérèse; Menegaux, Florence; Sanchez, Marie; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Pensotti, Valeria; Hopper, John L.; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C.; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Sigurdson, Alice J.; Doody, Michele M.; Hamann, Ute; Torres, Diana; Ulmer, Hans-Ulrich; Försti, Asta; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Marie Mulligan, Anna; Chenevix-Trench, Georgia; Balleine, Rosemary; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Lindblom, Annika; Margolin, Sara; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Eilber, Ursula; Wang-Gohrke, Shan; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; Koppert, Linetta B.; Carpenter, Jane; Clarke, Christine; Scott, Rodney; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Brenner, Hermann; Arndt, Volker; Stegmaier, Christa; Karina Dieffenbach, Aida; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Offit, Kenneth; Vijai, Joseph; Robson, Mark; Rau-Murthy, Rohini; Dwek, Miriam; Swann, Ruth; Annie Perkins, Katherine; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Eccles, Diana M.; Tapper, William J.; Rafiq, Sajjad; John, Esther M.; Whittemore, Alice S.; Slager, Susan; Yannoukakos, Drakoulis; Toland, Amanda E.; Yao, Song; Zheng, Wei; Halverson, Sandra L.; González-Neira, Anna; Pita, Guillermo; Rosario Alonso, M.; Álvarez, Nuria; Herrero, Daniel; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Healey, Catherine S.; Simard, Jacques; Hall, Per; Easton, Douglas F.; Garcia-Closas, Montserrat

    2015-01-01

    Background: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking. Methods: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates. Results: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer. Conclusions: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report. PMID:25855707

  5. Cross-cancer profiling of molecular alterations within the human autophagy interaction network.

    PubMed

    Lebovitz, Chandra B; Robertson, A Gordon; Goya, Rodrigo; Jones, Steven J; Morin, Ryan D; Marra, Marco A; Gorski, Sharon M

    2015-01-01

    Aberrant activation or disruption of autophagy promotes tumorigenesis in various preclinical models of cancer, but whether the autophagy pathway is a target for recurrent molecular alteration in human cancer patient samples is unknown. To address this outstanding question, we surveyed 211 human autophagy-associated genes for tumor-related alterations to DNA sequence and RNA expression levels and examined their association with patient survival outcomes in multiple cancer types with sequence data from The Cancer Genome Atlas consortium. We found 3 (RB1CC1/FIP200, ULK4, WDR45/WIPI4) and one (ATG7) core autophagy genes to be under positive selection for somatic mutations in endometrial carcinoma and clear cell renal carcinoma, respectively, while 29 autophagy regulators and pathway interactors, including previously identified KEAP1, NFE2L2, and MTOR, were significantly mutated in 6 of the 11 cancer types examined. Gene expression analyses revealed that GABARAPL1 and MAP1LC3C/LC3C transcripts were less abundant in breast cancer and non-small cell lung cancers than in matched normal tissue controls; ATG4D transcripts were increased in lung squamous cell carcinoma, as were ATG16L2 transcripts in kidney cancer. Unsupervised clustering of autophagy-associated mRNA levels in tumors stratified patient overall survival in 3 of 9 cancer types (acute myeloid leukemia, clear cell renal carcinoma, and head and neck cancer). These analyses provide the first comprehensive resource of recurrently altered autophagy-associated genes in human tumors, and highlight cancer types and subtypes where perturbed autophagy may be relevant to patient overall survival.

  6. Cross-cancer profiling of molecular alterations within the human autophagy interaction network

    PubMed Central

    Lebovitz, Chandra B; Robertson, A Gordon; Goya, Rodrigo; Jones, Steven J; Morin, Ryan D; Marra, Marco A; Gorski, Sharon M

    2015-01-01

    Aberrant activation or disruption of autophagy promotes tumorigenesis in various preclinical models of cancer, but whether the autophagy pathway is a target for recurrent molecular alteration in human cancer patient samples is unknown. To address this outstanding question, we surveyed 211 human autophagy-associated genes for tumor-related alterations to DNA sequence and RNA expression levels and examined their association with patient survival outcomes in multiple cancer types with sequence data from The Cancer Genome Atlas consortium. We found 3 (RB1CC1/FIP200, ULK4, WDR45/WIPI4) and one (ATG7) core autophagy genes to be under positive selection for somatic mutations in endometrial carcinoma and clear cell renal carcinoma, respectively, while 29 autophagy regulators and pathway interactors, including previously identified KEAP1, NFE2L2, and MTOR, were significantly mutated in 6 of the 11 cancer types examined. Gene expression analyses revealed that GABARAPL1 and MAP1LC3C/LC3C transcripts were less abundant in breast cancer and non-small cell lung cancers than in matched normal tissue controls; ATG4D transcripts were increased in lung squamous cell carcinoma, as were ATG16L2 transcripts in kidney cancer. Unsupervised clustering of autophagy-associated mRNA levels in tumors stratified patient overall survival in 3 of 9 cancer types (acute myeloid leukemia, clear cell renal carcinoma, and head and neck cancer). These analyses provide the first comprehensive resource of recurrently altered autophagy-associated genes in human tumors, and highlight cancer types and subtypes where perturbed autophagy may be relevant to patient overall survival. PMID:26208877

  7. Cohort Profile: the National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0.

    PubMed

    Van Hemelrijck, Mieke; Wigertz, Annette; Sandin, Fredrik; Garmo, Hans; Hellström, Karin; Fransson, Per; Widmark, Anders; Lambe, Mats; Adolfsson, Jan; Varenhorst, Eberhard; Johansson, Jan-Erik; Stattin, Pär

    2013-08-01

    In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case-control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.

  8. Home Schooling.

    ERIC Educational Resources Information Center

    Gordon, William M.; And Others

    Cases that address the issue of home schooling are summarized in this report. Organized chronologically, each case description includes quoted material from the court ruling. Issues involve parent actions regarding compulsory student enrollment, parent qualifications for home teaching, student certification, church-state separation, constitutional…

  9. Home Groups.

    ERIC Educational Resources Information Center

    Stahler, Theresa M.

    All students enrolled in the entry level foundations course in the College of Education of Kutztown University (Pennsylvania) participate in home groups, a cooperative learning strategy. Each student is assigned to a five- or six-person home group on the first day of class. Although group placements are made on the basis of class lists, every…

  10. The morphologies of breast cancer cell lines in three-dimensionalassays correlate with their profiles of gene expression

    SciTech Connect

    Kenny, Paraic A.; Lee, Genee Y.; Myers, Connie A.; Neve, RichardM.; Semeiks, Jeremy R.; Spellman, Paul T.; Lorenz, Katrin; Lee, Eva H.; Barcellos-Hoff, Mary Helen; Petersen, Ole W.; Gray, Joe W.; Bissell, MinaJ.

    2007-01-31

    3D cell cultures are rapidly becoming the method of choice for the physiologically relevant modeling of many aspects of non-malignant and malignant cell behavior ex vivo. Nevertheless, only a limited number of distinct cell types have been evaluated in this assay to date. Here we report the first large scale comparison of the transcriptional profiles and 3D cell culture phenotypes of a substantial panel of human breast cancer cell lines. Each cell line adopts a colony morphology of one of four main classes in 3D culture. These morphologies reflect, at least in part, the underlying gene expression profile and protein expression patterns of the cell lines, and distinct morphologies were also associated with tumor cell invasiveness and with cell lines originating from metastases. We further demonstrate that consistent differences in genes encoding signal transduction proteins emerge when even tumor cells are cultured in 3D microenvironments.

  11. KiSS1/GPR54 and estrogen-related gene expression profiles in primary breast cancer

    PubMed Central

    Kozłowski, Leszek; Milewski, Robert; Wołczyński, Sławomir

    2012-01-01

    The estrogen receptor α (ERα)-mediated pathway plays a critical role in breast cancer development and progression. KiSS1 was previously described as a metastasis suppressor gene in certain carcinomas. However, the role of KiSS1/GPR54 in breast cancer remains controversial. Whether the function of the KiSS1/GPR54 system depends on estrogen signaling in the breast cancer cell remains to be determined. This study aimed to determine the expression profiles of the KiSS1/GPR54, ERα, ERβ, aromatase and cyclin D1 genes in human breast cancer tissues, and to identify a possible link between the expression levels of the studied genes and the selected clinical and pathological features. The study subjects comprised 59 females treated surgically for primary breast cancer. Total RNA was extracted from frozen breast cancer tissues, and expression levels were examined to determine any correlations. We observed strong positive correlations between the expression levels of the studied genes. The expression of ERα correlated positively with progesterone receptors (PRs), and in these tumors we also observed positive correlations between KiSS1, GPR54 and cyclin D1 mRNAs and the ERα protein. ER-positive breast tumors exhibited higher KiSS1 and GPR54 levels than the ER-negative tumors. The expression levels of the ERα and GPR54 transcripts were higher in the moderately differentiated tumors (G2) compared to the poorly differentiated high-grade (G3) cancers. We also found that HER-2/neu status in breast cancer is negatively associated with GPR54 mRNA expression. Decreasing GPR54 mRNA expression levels in HER-2/neu (+) tumors may be associated with the deregulation of the classical estrogen-mediated signaling pathway in breast tumors, and therefore, with promotion of tumor invasiveness. Our findings indicate that genes involved in the KiSS1/GPR54 system, as well as in the estrogen signaling pathway, may be utilizable molecular factors in pathogenesis studies of breast cancer. PMID

  12. Profile of e-patients: analysis of their cancer information-seeking from a national survey.

    PubMed

    Kim, Kyunghye; Kwon, Nahyun

    2010-10-01

    Researchers have yet to fully understand how competent e-patients are in selecting and using health information sources, or, more importantly, who e-patients are. This study attempted to uncover how cancer e-patients differ from other cancer information seekers in terms of their sociodemographic background, social networks, information competence, and selection of cancer information sources. We analyzed data from the National Cancer Institute's 2005 Health Information National Trends Survey, and a series of chi-square tests showed that factors that distinguished cancer e-patients from other cancer information seekers were age, gender, education, employment status, health insurance, and membership in online support groups. They were not different in the other factors measured by the survey. Our logistic regression analysis revealed that the e-patients were older and talked about their health issues with friends or family more frequently compared with online health information seekers without cancer. While preferring information from their doctors over the Internet, e-patients used the Internet as their primary source. In contrast to previous literature, we found little evidence that e-patients were savvy health information consumers who could make informed decisions on their own health. The findings of this study addressed a need for a better design and delivery of health information literacy programs for cancer e-patients.

  13. Cytogenomic profiling of breast cancer brain metastases reveals potential for repurposing targeted therapeutics.

    PubMed

    Bollig-Fischer, Aliccia; Michelhaugh, Sharon K; Wijesinghe, Priyanga; Dyson, Greg; Kruger, Adele; Palanisamy, Nallasivam; Choi, Lydia; Alosh, Baraa; Ali-Fehmi, Rouba; Mittal, Sandeep

    2015-06-10

    Breast cancer brain metastases remain a significant clinical problem. Chemotherapy is ineffective and a lack of treatment options result in poor patient outcomes. Targeted therapeutics have proven to be highly effective in primary breast cancer, but lack of molecular genomic characterization of metastatic brain tumors is hindering the development of new treatment regimens. Here we contribute to fill this void by reporting on gene copy number variation (CNV) in 10 breast cancer metastatic brain tumors, assayed by array comparative genomic hybridization (aCGH). Results were compared to a list of cancer genes verified by others to influence cancer. Cancer gene aberrations were identified in all specimens and pathway-level analysis was applied to aggregate data, which identified stem cell pluripotency pathway enrichment and highlighted recurring, significant amplification of SOX2, PIK3CA, NTRK1, GNAS, CTNNB1, and FGFR1. For a subset of the metastatic brain tumor samples (n = 4) we compared patient-matched primary breast cancer specimens. The results of our CGH analysis and validation by alternative methods indicate that oncogenic signals driving growth of metastatic tumors exist in the original cancer. This report contributes support for more rapid development of new treatments of metastatic brain tumors, the use of genomic-based diagnostic tools and repurposed drug treatments.

  14. Cancer Patients' Use of Social Work Services in Canada: Prevalence, Profile, and Predictors of Use

    ERIC Educational Resources Information Center

    Gadalla, Tahany M.

    2007-01-01

    This study examines the demographic and physical and mental health characteristics of social work clients among cancer patients in Canada as compared with nonusers of social work services, and factors that affect use of social work services among cancer patients. On the basis of data from two cycles of the Canadian Community Health Survey, the…

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

    DTIC Science & Technology

    2013-10-01

    Heymach JV, Lippman SM. Lung cancer. N Engl J Med. 2008;359:1367-80. 3. Slaughter DP, Southwick HW, Smejkal W. Field cancerization in oral stratified...Schembri F, Gilman S, Dumas YM, Calner P, Sebastiani P, Sridhar S, Beamis J, Lamb C, Anderson T, Gerry N, Keane J, Lenburg ME, Brody JS. Airway

  16. Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels

    NASA Astrophysics Data System (ADS)

    Islam, Muhymin; Motasim Bellah, Mohammad; Sajid, Adeel; Raziul Hasan, Mohammad; Kim, Young-Tae; Iqbal, Samir M.

    2015-09-01

    Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer.

  17. Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels.

    PubMed

    Islam, Muhymin; Bellah, Mohammad Motasim; Sajid, Adeel; Hasan, Mohammad Raziul; Kim, Young-tae; Iqbal, Samir M

    2015-09-16

    Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer.

  18. Molecular and clinical profiles of syndecan-1 in solid and hematological cancer for prognosis and precision medicine

    PubMed Central

    Akl, Mohamed R.; Nagpal, Poonam; Ayoub, Nehad M.; Prabhu, Sathyen A.; Gliksman, Matthew; Tai, Betty; Hatipoglu, Ahmet; Goy, Andre; Suh, K. Stephen

    2015-01-01

    Syndecan-1 (SDC1, CD138) is a key cell surface adhesion molecule essential for maintaining cell morphology and interaction with the surrounding microenvironment. Deregulation of SDC1 contributes to cancer progression by promoting cell proliferation, metastasis, invasion and angiogenesis, and is associated with relapse through chemoresistance. SDC1 expression level is also associated with responses to chemotherapy and with prognosis in multiple solid and hematological cancers, including multiple myeloma and Hodgkin lymphoma. At the tissue level, the expression levels of SDC1 and the released extracellular domain of SDC1 correlate with tumor malignancy, phenotype, and metastatic potential for both solid and hematological tumors in a tissue-specific manner. The SDC1 expression profile varies among cancer types, but the differential expression signatures between normal and cancer cells in epithelial and stromal compartments are directly associated with aggressiveness of tumors and patient's clinical outcome and survival. Therefore, relevant biomarkers of SDC signaling may be useful for selecting patients that would most likely respond to a particular therapy at the time of diagnosis or perhaps for predicting relapse. In addition, the reciprocal expression signature of SDC between tumor epithelial and stromal compartments may have synergistic value for patient selection and the prediction of clinical outcome. PMID:26293675

  19. Effects of Nanotexture on Electrical Profiling of Single Tumor Cell and Detection of Cancer from Blood in Microfluidic Channels

    PubMed Central

    Islam, Muhymin; Motasim Bellah, Mohammad; Sajid, Adeel; Raziul Hasan, Mohammad; Kim, Young-tae; Iqbal, Samir M.

    2015-01-01

    Microfluidic channels have been implemented to detect cancer cells from blood using electrical measurement of each single cell from the sample. Every cell provided characteristic current profile based on its mechano-physical properties. Cancer cells not only showed higher translocation time and peak amplitude compared to blood cells, their pulse shape was also distinctively different. Prevalent microfluidic channels are plain but we created nanotexture on the channel walls using micro reactive ion etching (micro-RIE). The translocation behaviors of the metastatic renal cancer cells through plain and nanotextured PDMS microchannels showed clear differences. Nanotexture enhanced the cell-surface interactions and more than 50% tumor cells exhibited slower translocation through nanotextured channels compared to plain devices. On the other hand, most of the blood cells had very similar characteristics in both channels. Only 7.63% blood cells had slower translocation in nanotextured microchannels. The tumor cell detection efficiency from whole blood increased by 14% in nanotextured microchannels compared to plain channels. This interesting effect of nanotexture on translocation behavior of tumor cells is important for the early detection of cancer. PMID:26373820

  20. Activatable and Cell-Penetrable Multiplex FRET Nanosensor for Profiling MT1-MMP Activity in Single Cancer Cells

    PubMed Central

    Chung, Eddie Y.; Ochs, Christopher J.; Wang, Yi; Lei, Lei; Qin, Qin; Smith, Andrew M.; Strongin, Alex Y.; Kamm, Roger; Qi, Ying-Xin; Lu, Shaoying; Wang, Yingxiao

    2015-01-01

    We developed a quantum-dot-based fluorescence resonance energy transfer (QD-FRET) nanosensor to visualize the activity of matrix metalloproteinase (MT1-MMP) at cell membrane. A bended peptide with multiple motifs was engineered to position the FRET pair at a close proximity to allow energy transfer, which can be cleaved by active MT1-MMP to result in FRET changes and the exposure of cell penetrating sequence. Via FRET and penetrated QD signals, the nanosensor can profile cancer cells. PMID:26203778

  1. Parallel Profiles of Inflammatory and Effector Memory T Cells in Visceral Fat and Liver of Obesity-Associated Cancer Patients.

    PubMed

    Conroy, Melissa J; Galvin, Karen C; Doyle, Suzanne L; Kavanagh, Maria E; Mongan, Ann-Marie; Cannon, Aoife; Moore, Gillian Y; Reynolds, John V; Lysaght, Joanne

    2016-10-01

    In the midst of a worsening obesity epidemic, the incidence of obesity-associated morbidities, including cancer, diabetes, cardiac and liver disease is increasing. Insights into mechanisms underlying pathological obesity-associated inflammation are lacking. Both the omentum, the principal component of visceral fat, and liver of obese individuals are sites of excessive inflammation, but to date the T cell profiles of both compartments have not been assessed or compared in a patient cohort with obesity-associated disease. We have previously identified that omentum is enriched with inflammatory cytokines, chemokines and T cells. Here, we compared the inflammatory profile of T cells in the omentum and liver of patients with the obesity-associated malignancy oesophageal adenocarcinoma (OAC). Furthermore, we assessed the secreted cytokine profile in OAC patient serum, omentum and liver to assess systemic and local inflammation. We observed parallel T cell cytokine profiles and phenotypes in the omentum and liver of OAC patients, in particular CD69(+) and inflammatory effector memory T cells. This study reflects similar processes of inflammation and T cell activation in the omentum and liver, and may suggest common targets to modulate pathological inflammation at these sites.

  2. Quantitative Profiling of Protein Tyrosine Kinases in Human Cancer Cell Lines by Multiplexed Parallel Reaction Monitoring Assays*

    PubMed Central

    Kim, Hye-Jung; Lin, De; Lee, Hyoung-Joo; Li, Ming; Liebler, Daniel C.

    2016-01-01

    Protein tyrosine kinases (PTKs) play key roles in cellular signal transduction, cell cycle regulation, cell division, and cell differentiation. Dysregulation of PTK-activated pathways, often by receptor overexpression, gene amplification, or genetic mutation, is a causal factor underlying numerous cancers. In this study, we have developed a parallel reaction monitoring-based assay for quantitative profiling of 83 PTKs. The assay detects 308 proteotypic peptides from 54 receptor tyrosine kinases and 29 nonreceptor tyrosine kinases in a single run. Quantitative comparisons were based on the labeled reference peptide method. We implemented the assay in four cell models: 1) a comparison of proliferating versus epidermal growth factor-stimulated A431 cells, 2) a comparison of SW480Null (mutant APC) and SW480APC (APC restored) colon tumor cell lines, and 3) a comparison of 10 colorectal cancer cell lines with different genomic abnormalities, and 4) lung cancer cell lines with either susceptibility (11–18) or acquired resistance (11–18R) to the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib. We observed distinct PTK expression changes that were induced by stimuli, genomic features or drug resistance, which were consistent with previous reports. However, most of the measured expression differences were novel observations. For example, acquired resistance to erlotinib in the 11–18 cell model was associated not only with previously reported up-regulation of MET, but also with up-regulation of FLK2 and down-regulation of LYN and PTK7. Immunoblot analyses and shotgun proteomics data were highly consistent with parallel reaction monitoring data. Multiplexed parallel reaction monitoring assays provide a targeted, systems-level profiling approach to evaluate cancer-related proteotypes and adaptations. Data are available through Proteome eXchange Accession PXD002706. PMID:26631510

  3. Transcriptional profiling of breast cancer cells in response to mevinolin: Evidence of cell cycle arrest, DNA degradation and apoptosis

    PubMed Central

    MAHMOUD, ALI M.; ABOUL-SOUD, MOURAD A.M.; HAN, JUNKYU; AL-SHEIKH, YAZEED A.; AL-ABD, AHMED M.; EL-SHEMY, HANY A.

    2016-01-01

    The merging of high-throughput gene expression techniques, such as microarray, in the screening of natural products as anticancer agents, is considered the optimal solution for gaining a better understanding of the intervention mechanism. Red yeast rice (RYR), a Chinese dietary product, contains a mixture of hypocholesterolemia agents such as statins. Typically, statins have this effect via the inhibition of HMG-CoA reductase, the key enzyme in the biosynthesis of cholesterol. Recently, statins have been shown to exhibit various beneficial antineoplastic properties through the disruption of tumor angiogenesis and metastatic processes. Mevinolin (MVN) is a member of statins and is abundantly present in RYR. Early experimental trials suggested that the mixed apoptotic/necrotic cell death pathway is activated in response to MVN exposure. In the current study, the cytotoxic profile of MVN was evaluated against MCF-7, a breast cancer-derived cell line. The obtained results indicated that MVN-induced cytotoxicity is multi-factorial involving several regulatory pathways in the cytotoxic effects of MVN on breast cancer cell lines. In addition, MVN-induced transcript abundance profiles inferred from microarrays showed significant changes in some key cell processes. The changes were predicted to induce cell cycle arrest and reactive oxygen species generation but inhibit DNA repair and cell proliferation. This MVN-mediated multi-factorial stress triggered specific programmed cell death (apoptosis) and DNA degradation responses in breast cancer cells. Taken together, the observed MVN-induced effects underscore the potential of this ubiquitous natural compound as a selective anticancer activity, with broad safety margins and low cost compared to benchmarked traditional synthetic chemotherapeutic agents. Additionally, the data support further pre-clinical and clinical evaluations of MVN as a novel strategy to combat breast cancer and overcome drug resistance. PMID:26983896

  4. Pattern Analysis and Decision Support for Cancer through Clinico-Genomic Profiles

    NASA Astrophysics Data System (ADS)

    Exarchos, Themis P.; Giannakeas, Nikolaos; Goletsis, Yorgos; Papaloukas, Costas; Fotiadis, Dimitrios I.

    Advances in genome technology are playing a growing role in medicine and healthcare. With the development of new technologies and opportunities for large-scale analysis of the genome, genomic data have a clear impact on medicine. Cancer prognostics and therapeutics are among the first major test cases for genomic medicine, given that all types of cancer are related with genomic instability. In this paper we present a novel system for pattern analysis and decision support in cancer. The system integrates clinical data from electronic health records and genomic data. Pattern analysis and data mining methods are applied to these integrated data and the discovered knowledge is used for cancer decision support. Through this integration, conclusions can be drawn for early diagnosis, staging and cancer treatment.

  5. A profile of enzalutamide for the treatment of advanced castration resistant prostate cancer

    PubMed Central

    Greasley, Rosa; Khabazhaitajer, Mohammad; Rosario, Derek J

    2015-01-01

    Recent advances in understanding the mechanisms underlying the development and progression of castration resistant prostate cancer from androgen-sensitive prostate cancer have provided new avenues exploring efficacious therapies in a disease which is the second leading cause of cancer deaths among men in the western world. In the evolution of second generation anti-androgens, enzalutamide, a novel androgen-receptor signaling inhibitor, has emerged targeting multiple steps within the androgenic stimulation pathway. This review discusses what is currently known of the mechanisms surrounding castration resistant prostate cancer development and the current human clinical trials to determine whether enzalutamide presents a new hope for men with advanced prostate cancer. The issues of therapy resistance, withdrawal effects and cross-resistance are briefly touched upon. PMID:26109877

  6. Personalized Home-based Interval Exercise Training May Improve Cardiorespiratory Fitness in Cancer Patients Preparing to Undergo Hematopoietic Cell Transplantation

    PubMed Central

    Wood, William A; Phillips, Brett; Smith-Ryan, Abbie E; Wilson, Doug; Deal, Allison M; Bailey, Charlotte; Meeneghan, Mathew; Reeve, Bryce B; Basch, Ethan M; Bennett, Antonia V; Shea, Thomas C; Battaglini, Claudio L

    2016-01-01

    Impaired cardiorespiratory fitness is associated with inferior survival in patients preparing to undergo hematopoietic cell transplantation (HCT). Exercise training based on short, higher-intensity intervals has the potential to efficiently improve cardiorespiratory fitness. We studied home-based interval exercise training (IET) in 40 patients prior to autologous (N=20) or allogeneic (N=20) HCT. Each session consisted of 5, three-minute intervals of walking, jogging, or cycling at 65-95% maximal heart rate (MHR) with 3 minutes of low intensity exercise (<65% MHR) between intervals. Participants were asked to perform sessions at least 3 times weekly. The duration of the intervention was at least 6 weeks, depending on each patient’s scheduled transplantation date. Cardiorespiratory fitness was assessed from a peak oxygen consumption test (VO2peak) and a 6 minute walk (6MWD) before and after the intervention period. For the autologous HCT cohort, improvements in VO2peak (p=0.12) and 6MWD (p=0.19) were not statistically significant. For the allogeneic cohort, the median VO2peak improvement was 3.7ml/kg*min (p=0.005) and the median 6MWD improvement was 34 meters (p=0.006). Home-based, interval exercise training can be performed prior to HCT and has the potential to improve cardiorespiratory fitness. PMID:26999467

  7. Building America Top Innovations 2012: Affordable High Performance in Production Homes: Artistic Homes

    SciTech Connect

    none,

    2013-01-01

    This Building America Top Innovations profile describes Artistic Homes, a successful New Mexico production builder, who went from code-minimum to under HERS 50 standard on every home, with optional PV upgrades to HERS 35 or true net zero on every home plan offered.

  8. Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines

    PubMed Central

    Calcagno, Danielle Queiroz; Takeno, Sylvia Santomi; Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Wisnieski, Fernanda; Chen, Elizabeth Suchi; Araújo, Taíssa Maíra Thomaz; Lima, Eleonidas Moura; Melaragno, Maria Isabel; Demachki, Samia; Assumpção, Paulo Pimentel; Burbano, Rommel Rodriguez; Smith, Marília Cardoso

    2016-01-01

    AIM To identify common copy number alterations on gastric cancer cell lines. METHODS Four gastric cancer cell lines (ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis. RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha (IL11RA) and maternal embryonic leucine zipper kinase (MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11RA and MELK was observed in 19.1% (13/68) and 55.9% (38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer. PMID:27920471

  9. Mass spectrometry-based quantitative metabolomics revealed a distinct lipid profile in breast cancer patients.

    PubMed

    Qiu, Yunping; Zhou, Bingsen; Su, Mingming; Baxter, Sarah; Zheng, Xiaojiao; Zhao, Xueqing; Yen, Yun; Jia, Wei

    2013-04-12

    Breast cancer accounts for the largest number of newly diagnosed cases in female cancer patients. Although mammography is a powerful screening tool, about 20% of breast cancer cases cannot be detected by this method. New diagnostic biomarkers for breast cancer are necessary. Here, we used a mass spectrometry-based quantitative metabolomics method to analyze plasma samples from 55 breast cancer patients and 25 healthy controls. A number of 30 patients and 20 age-matched healthy controls were used as a training dataset to establish a diagnostic model and to identify potential biomarkers. The remaining samples were used as a validation dataset to evaluate the predictive accuracy for the established model. Distinct separation was obtained from an orthogonal partial least squares-discriminant analysis (OPLS-DA) model with good prediction accuracy. Based on this analysis, 39 differentiating metabolites were identified, including significantly lower levels of lysophosphatidylcholines and higher levels of sphingomyelins in the plasma samples obtained from breast cancer patients compared with healthy controls. Using logical regression, a diagnostic equation based on three metabolites (lysoPC a C16:0, PC ae C42:5 and PC aa C34:2) successfully differentiated breast cancer patients from healthy controls, with a sensitivity of 98.1% and a specificity of 96.0%.

  10. iTRAQ-based proteomic profiling of breast cancer cell response to doxorubicin and TRAIL.

    PubMed

    Leong, Sharon; Nunez, Andrea C; Lin, Mike Z; Crossett, Ben; Christopherson, Richard I; Baxter, Robert C

    2012-07-06

    Breast cancer is a molecularly heterogeneous disease, and predicting response to chemotherapy remains a major clinical challenge. To minimize adverse side-effects or cumulative toxicity in patients unlikely to benefit from treatment, biomarkers indicating treatment efficacy are critically needed. iTRAQ labeling coupled with multidimensional LC-MS/MS of the enriched mitochondria and endoplasmic reticulum fraction, key organelles regulating apoptosis, has led to the discovery of several differentially abundant proteins in breast cancer cells treated with the chemotherapeutic agent doxorubicin followed by the death receptor ligand, TRAIL, among 571 and 801 unique proteins identified in ZR-75-1 and MDA-MB-231 breast cancer cell lines, respectively. The differentially abundant proteins represent diverse biological processes associated with cellular assembly and organization, molecular transport, oxidative stress, cell motility, cell death, and cancer. Despite many differences in molecular phenotype between the two breast cancer cell lines, a comparison of their subproteomes following drug treatment revealed three proteins displaying common regulation: PPIB, AHNAK, and SLC1A5. Changes in these proteins, detected by iTRAQ, were confirmed by immunofluorescence, visualized by confocal microscopy. These novel potential biomarkers may have clinical utility for assessing response to cancer treatment and may provide insight into new therapeutic targets for breast cancer.

  11. Expression profiles of loneliness-associated genes for survival prediction in cancer patients.

    PubMed

    You, Liang-Fu; Yeh, Jia-Rong; Su, Mu-Chun

    2014-01-01

    Influence of loneliness on human survival has been established epidemiologically, but genomic research remains undeveloped. We identified 34 loneliness-associated genes which were statistically significant for high- lonely and low-lonely individuals. With the univariate Cox proportional hazards regression model, we obtained corresponding regression coefficients for loneliness-associated genes fo individual cancer patients. Furthermore, risk scores could be generated with the combination of gene expression level multiplied by corresponding regression coefficients of loneliness-associated genes. We verified that high-risk score cancer patients had shorter mean survival time than their low-risk score counterparts. Then we validated the loneliness-associated gene signature in three independent brain cancer cohorts with Kaplan-Meier survival curves (n=77, 85 and 191), significantly separable by log-rank test with hazard ratios (HR) >1 and p-values <0.0001 (HR=2.94, 3.82, and 1.78). Moreover, we validated the loneliness-associated gene signature in bone cancer (HR=5.10, p-value=4.69e-3), lung cancer (HR=2.86, p-value=4.71e-5), ovarian cancer (HR=1.97, p-value=3.11e-5), and leukemia (HR=2.06, p-value=1.79e-4) cohorts. The last lymphoma cohort proved to have an HR=3.50, p-value=1.15e-7. Loneliness- associated genes had good survival prediction for cancer patients, especially bone cancer patients. Our study provided the first indication that expression of loneliness-associated genes are related to survival time of cancer patients.

  12. Lymphocytic profiling in thyroid cancer provides clues for failure of tumor immunity.

    PubMed

    Imam, Shahnawaz; Paparodis, Rodis; Sharma, Deepak; Jaume, Juan Carlos

    2014-06-01

    Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not well understood. The fact that cancer can survive in this adverse microenvironment is indicative of immune regulation. We characterized the lymphocytic infiltration that accompanies thyroid cancer and compared it with that present in thyroid autoimmunity. We found that double-negative (DN) T cells were significantly more abundant in thyroid cancer than in thyroid autoimmunity. Although FOXP3(+) regulatory T cells were also present, DN T cells were the dominant cell type, associated with thyroid cancer. Furthermore, upon stimulation, the DN T cells associated with cancer remained unchanged, while the few (<5%) DN T cells associated with thyroid autoimmunity increased in numbers (>20%). CD25 expression on DN T cells remained unchanged after stimulation, which indicates that the increase in the absolute number of DN T cells in thyroid autoimmunity was at the expense of inactivation of single-positive T cells. We concluded that in the setting of thyroid cancer, DN T cells appear to suppress tumor immunity. In contrast, in thyroid autoimmunity, DN T cells were barely present and only increased at the expense of inactivated, single-positive T cells upon induction. Together, these findings indicate that thyroid cancer-associated DN T cells might regulate proliferation and effector function of T cells and thereby contribute to tumor tolerance and active avoidance of tumor immunity.

  13. Microarray profiling of mononuclear peripheral blood cells identifies novel candidate genes related to chemoradiation response in rectal cancer.

    PubMed

    Palma, Pablo; Cuadros, Marta; Conde-Muíño, Raquel; Olmedo, Carmen; Cano, Carlos; Segura-Jiménez, Inmaculada; Blanco, Armando; Bueno, Pablo; Ferrón, J Antonio; Medina, Pedro

    2013-01-01

    Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders). Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11) and non-responders (n = 16) to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029) gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with locally advanced

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

    EPA Science Inventory

    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....

  15. Reproductive and Hormonal Risk Profile According to Language Acculturation and Country of Residence in the Ella Binational Breast Cancer Study

    PubMed Central

    Gallo, Linda; Cooper, Renee; Wertheim, Betsy C.; Natarajan, Loki; Thompson, Patricia A.; Komenaka, Ian K.; Brewster, Abenaa; Bondy, Melissa; Daneri-Navarro, Adrian; Meza-Montenegro, María Mercedes; Gutierrez-Millan, Luis Enrique; Martínez, María Elena

    2014-01-01

    Abstract Background: We compared the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent. Methods: To compare the distribution of breast cancer reproductive and hormonal risk factors by level of acculturation and country of residence in women of Mexican descent, taking into account level of education, we analyzed data on 581 Mexican and 620 Mexican American (MA) women with a history of invasive breast cancer from the Ella Binational Breast Cancer Study. An eight-item language-based acculturation measure was used to classify MA women. Multivariate logistic regression was used to test associations between language acculturation, country of residence, and reproductive and hormonal risk factors. Results: After adjustment for age and education, compared to women residing in Mexico, English-dominant MAs were significantly more likely to have an earlier age at menarche (<12 years; odds ratio [OR]=2.08; 95% confidence interval [CI], 1.30–3.34), less likely to have a late age at first birth (≥30 years; OR=0.49; 95% CI, 0.25–0.97), and less likely to ever breastfeed (OR=0.13; 95% CI, 0.08–0.21). Conclusions: Differences in reproductive and hormonal risk profile according to language acculturation and country of residence are evident; some of these were explained by education. Results support continued efforts to educate Mexican and MA women on screening and early detection of breast cancer along with promotion of modifiable factors, such as breastfeeding. PMID:24475760

  16. Effect of D-allose on prostate cancer cell lines: phospholipid profiling by nanoflow liquid chromatography-tandem mass spectrometry.

    PubMed

    Jeong, Rae Ung; Lim, Sangsoo; Kim, Myoung Ok; Moon, Myeong Hee

    2011-08-01

    D-Allose, a rare, naturally occurring monosaccharide, is known to exert anti-proliferative effects on cancer cells. The effects of D-allose on the cellular membranes of hormone-refractory prostate cancer cell line (DU145), hormone-sensitive prostate cancer cell line (LNCaP), and normal prostate epithelial cells (PrEC) were studied at the molecular level by phospholipid (PL) profiling using a shotgun lipidomic method. The molecular structures of 85 PL species including 23 phosphatidylcholines, 12 phosphatidylethanolamines (PEs), 11 phosphatidylserines (PSs), 16 phosphatidylinositols, 9 phosphatidic acids (PAs), and 14 phosphatidylglycerols (PGs) were identified by data-dependent collision-induced dissociation of nanoflow liquid chromatography-tandem mass spectrometry, and the PL amounts were quantified. The addition of D-allose to prostate cancer cell lines during their growth phases had negligible or decreased effects on the relative regulation of PL species, but several new PS molecules (two for DU145 and three for LNCaP) emerged. In contrast, experiments on the PrEC cell line revealed that some high abundant species (14:0/14:0-PE, 16:2/16:0-PG, and 20:6/18:1-PA) showed significant increases in concentration. These findings support a mechanism for the anti-proliferative effect of D-allose on prostate cancer cell lines that involves the induction of programmed cell death since PS molecules are known to induce apoptosis. Principal component analysis was carried out to examine differences in PL distributions among the three cell lines promoted by D-allose.

  17. Tumor Genomic Profiling in Breast Cancer Patients Using Targeted Massively Parallel Sequencing

    DTIC Science & Technology

    2015-04-30

    exome sequencing to identify genomic mechanisms of therapeutic resistance The goal of this aim is perfotm whole exome sequencing in breast cancer...identify novel resistance mechanisms . Of the 72 patients described above, we have been able to obtain matched pre-treatment primary tissues from 28...advanced breast cancer, and novel strategies to overcome resistance mechanisms . If widely deployed, implementation of this approach may open new

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

    DTIC Science & Technology

    2011-10-01

    as well as DNA sequence changes of any length attributable to insertion or deletion of the microsatellite one- to four-base DNA repeating units... targeted via chemoprevention strategies. The revolution in “-omics” approaches will make high throughput studies of this region feasible and hold the key...Veterans. INTRODUCTION: Lung cancer continues to be the leading cause of cancer- related death in both men and women in the United States. The

  19. Proteomic profiling of NCI-60 extracellular vesicles uncovers common protein cargo and cancer type-specific biomarkers

    PubMed Central

    Liu, Xia; Singh, Rakesh K.; Meckes, David G.

    2016-01-01

    Packed with biological information, extracellular vesicles (EVs) offer exciting promise for biomarker discovery and applications in therapeutics and non-invasive diagnostics. Currently, our understanding of EV contents is confined by the limited cells from which vesicles have been characterized utilizing the same enrichment method. Using sixty cell lines from the National Cancer Institute (NCI-60), here we provide the largest proteomic profile of EVs in a single study, identifying 6,071 proteins with 213 common to all isolates. Proteins included established EV markers, and vesicular trafficking proteins such as Rab GTPases and tetraspanins. Differentially-expressed proteins offer potential for cancer diagnosis and prognosis. Network analysis of vesicle quantity and proteomes identified EV components associated with vesicle secretion, including CD81, CD63, syntenin-1, VAMP3, Rab GTPases, and integrins. Integration of vesicle proteomes with whole-cell molecular profiles revealed similarities, suggesting EVs provide a reliable reflection of their progenitor cell content, and are therefore excellent indicators of disease. PMID:27894104

  20. Urolithiasis, Urinary Cancer, and Home Drinking Water Source in the United States Territory of Guam, 2006–2010

    PubMed Central

    Haddock, Robert L.; Olson, David R.; Backer, Lorraine; Malilay, Josephine

    2016-01-01

    We reviewed patient records with a first-listed diagnosis of urolithiasis—also known as urinary tract or kidney stone disease, nephrolithiasis—upon discharge from Guam’s sole civilian hospital during 2006 to 2010 and urinary cancer mortality records from the Guam Cancer Registry for 1970 to 2009 to determine the source of municipal water supplied to the patients’ residence. The objective was to investigate a possible relationship between the sources of municipal water supplied to Guam villages and the incidence of urolithiasis and urinary cancer. We analyzed hospital discharge diagnoses of urolithiasis or renal calculi by calculating the incidence of first-mentioned discharge for urolithiasis or renal calculi and comparing rates across demographic or geographic categories while adjusting by age, sex, and ethnicity/race. We reviewed cancer registry records of urinary cancer deaths by patient residence. The annual incidence of hospitalization for urolithiasis was 5.22 per 10,000. Rates adjusted for sex or age exhibited almost no change. The rate of 9.83 per 10,000 among Chamorros was significantly higher (p < 0.05) than the rates among any other ethnic group or race. When villages were grouped by water source, rates of patients discharged with a first-listed diagnosis of urolithiasis, adjusted for ethnicity/race, were similar for villages using either well water (5.44 per 10,000) or mixed source water (5.39 per 10,000), and significantly greater than the rate for villages using exclusively reservoir water (1.35 per 10,000). No statistically significant differences were found between the water source or village of residence and urinary cancer mortality. Some Guam residents living in villages served completely or partly by deep well water high in calcium carbonate may be at increased risk for urolithiasis compared with residents living in villages served by surface waters. Although the risk appears to be highest in villagers of Chamorro ethnicity, residents

  1. Urolithiasis, Urinary Cancer, and Home Drinking Water Source in the United States Territory of Guam, 2006-2010.

    PubMed

    Haddock, Robert L; Olson, David R; Backer, Lorraine; Malilay, Josephine

    2016-05-24

    We reviewed patient records with a first-listed diagnosis of urolithiasis-also known as urinary tract or kidney stone disease, nephrolithiasis-upon discharge from Guam's sole civilian hospital during 2006 to 2010 and urinary cancer mortality records from the Guam Cancer Registry for 1970 to 2009 to determine the source of municipal water supplied to the patients' residence. The objective was to investigate a possible relationship between the sources of municipal water supplied to Guam villages and the incidence of urolithiasis and urinary cancer. We analyzed hospital discharge diagnoses of urolithiasis or renal calculi by calculating the incidence of first-mentioned discharge for urolithiasis or renal calculi and comparing rates across demographic or geographic categories while adjusting by age, sex, and ethnicity/race. We reviewed cancer registry records of urinary cancer deaths by patient residence. The annual incidence of hospitalization for urolithiasis was 5.22 per 10,000. Rates adjusted for sex or age exhibited almost no change. The rate of 9.83 per 10,000 among Chamorros was significantly higher (p < 0.05) than the rates among any other ethnic group or race. When villages were grouped by water source, rates of patients discharged with a first-listed diagnosis of urolithiasis, adjusted for ethnicity/race, were similar for villages using either well water (5.44 per 10,000) or mixed source water (5.39 per 10,000), and significantly greater than the rate for villages using exclusively reservoir water (1.35 per 10,000). No statistically significant differences were found between the water source or village of residence and urinary cancer mortality. Some Guam residents living in villages served completely or partly by deep well water high in calcium carbonate may be at increased risk for urolithiasis compared with residents living in villages served by surface waters. Although the risk appears to be highest in villagers of Chamorro ethnicity, residents should be

  2. Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast cancers

    PubMed Central

    Lee, Ji-Hyun; Zhao, Xing-Ming; Yoon, Ina; Lee, Jin Young; Kwon, Nam Hoon; Wang, Yin-Ying; Lee, Kyung-Min; Lee, Min-Joo; Kim, Jisun; Moon, Hyeong-Gon; In, Yongho; Hao, Jin-Kao; Park, Kyung-Mii; Noh, Dong-Young; Han, Wonshik; Kim, Sunghoon

    2016-01-01

    Despite the explosion in the numbers of cancer genomic studies, metastasis is still the major cause of cancer mortality. In breast cancer, approximately one-fifth of metastatic patients survive 5 years. Therefore, detecting the patients at a high risk of developing distant metastasis at first diagnosis is critical for effective treatment strategy. We hereby present a novel systems biology approach to identify driver mutations escalating the risk of metastasis based on both exome and RNA sequencing of our collected 78 normal-paired breast cancers. Unlike driver mutations occurring commonly in cancers as reported in the literature, the mutations detected here are relatively rare mutations occurring in less than half metastatic samples. By supposing that the driver mutations should affect the metastasis gene signatures, we develop a novel computational pipeline to identify the driver mutations that affect transcription factors regulating metastasis gene signatures. We identify driver mutations in ADPGK, NUP93, PCGF6, PKP2 and SLC22A5, which are verified to enhance cancer cell migration and prompt metastasis with in vitro experiments. The discovered somatic mutations may be helpful for identifying patients who are likely to develop distant metastasis. PMID:27625789

  3. Integrative analysis of mutational and transcriptional profiles reveals driver mutations of metastatic breast <