Science.gov

Sample records for cancer profiles home

  1. Bringing cancer care home.

    PubMed

    Treco-Jones, S

    1991-01-01

    Community hospitals in the South are seeing new and more cancer patients. Hospitals aggressively seeking new and faster methods to treat patients in their home towns bring benefits to both. PMID:10115667

  2. Genetics Home Reference: breast cancer

    MedlinePlus

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

  3. Genetics Home Reference: lung cancer

    MedlinePlus

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

  4. State Cancer Profiles

    MedlinePlus

    ... Data 2012 USCS Incidence Data 2013 American Community Survey Data 2013 Small Area Health Insurance Estimates Cancer Knowledge Maps Site Home Policies Accessibility FOIA Contact Us U.S. Department of Health and Human Services | National Institutes of Health | National Cancer Institute | USA.gov ...

  5. 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.

  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. Genetics Home Reference: bladder cancer

    MedlinePlus

    ... chemicals. Studies suggest that chronic bladder inflammation, a parasitic infection called schistosomiasis, and some medications used to treat ... Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Patient Support and Advocacy Resources (2 links) American Cancer ...

  9. Vocational Home Economics Teacher Educators: A Profile.

    ERIC Educational Resources Information Center

    Sullivan, Deborah; Redick, Sharon S.

    1991-01-01

    A total of 188 usable responses from 227 home economics teacher educators identified variables that raise job satisfaction (age, salary, program location in home economics department/college) and lower it (higher degree, never married, teaching load, institution with high enrollment). Overall, teacher educators had high job satisfaction. (SK)

  10. Cancer Patients Who Choose to Die At Home Live Longer

    MedlinePlus

    ... suggest that doctors shouldn't hesitate to allow dying cancer patients to receive palliative care at home, ... people would like to be at home when dying, but there have been concerns about whether the ...

  11. Genomic profiling of breast cancer.

    PubMed

    Pandey, Anjita; Singh, Alok Kumar; Maurya, Sanjeev Kumar; Rai, Rajani; Tewari, Mallika; Kumar, Mohan; Shukla, Hari S

    2009-05-01

    Genome study provides significant changes in the advancement of molecular diagnosis and treatment in Breast cancer. Several recent critical advances and high-throughput techniques identified the genomic trouble and dramatically accelerated the pace of research in preventing and curing this malignancy. Tumor-suppressor genes, proto-oncogenes, DNA-repair genes, carcinogen-metabolism genes are critically involved in progression of breast cancer. We reviewed imperative finding in breast genetics, ongoing work to segregate further susceptible genes, and preliminary studies on molecular profiling. PMID:19235775

  12. "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. PMID:10538737

  13. A State Profile of IT Sophistication in Nursing Homes

    PubMed Central

    Alexander, Gregory L.

    2008-01-01

    In healthcare, IT sophistication has been defined as the diversity and maturity of information system hardware and software that support clinical services. Clinical services relevant to this study include resident care management, clinical support and administrative activities in nursing homes. An IT sophistication survey previously validated in acute care settings and adapted for nursing homes was used to develop a state profile of Missouri nursing homes. The IT survey was disseminated via paper and electronic methods as chosen by a selected responder that had IT oversight and knowledge of IT stakeholders. A census of 199 respondents completed the survey, representing a 41% (199/491) response rate. Findings support recent literature indicating a higher percentage of nursing homes are still using technology for administrative purposes; however, there is growing recognition that technologies with greater functionality, is used more extensively for electronic and automated transfer of resident care information. PMID:18999316

  14. 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. PMID:24479985

  15. Psychological Correlates of Survival in Nursing Home Cancer Patients.

    ERIC Educational Resources Information Center

    Stein, Shayna; And Others

    1989-01-01

    Analyzed demographic, cancer, physical functioning and psychological data for late-stage cancer, newly admitted nursing home patients (n=90). Concluded that, compared to survivors, those who died within a three-month period more often acknowledged their condition as terminal, anticipated greater environmental stress and adjustment problems and had…

  16. 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…

  17. Classifying pancreatic cancer using gene expression profiling

    PubMed Central

    Ayars, Michael; Goggins, Michael

    2016-01-01

    Despite some advances in our understanding of the molecular characteristics of pancreatic cancer, much more progress is needed. In a new study, RNA profiling of pancreatic cancers was used to identify gene signatures of tumour cells and stromal cells to help predict patient outcomes. PMID:26484444

  18. Integrated Molecular Profiling in Advanced Cancers Trial

    ClinicalTrials.gov

    2016-08-19

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

  19. Home Remedy for Skin Cancer May Cause Damage, Mask New Growth

    MedlinePlus

    ... medlineplus/news/fullstory_158984.html Home Remedy For Skin Cancer May Cause Damage, Mask New Growth 'Black ... promise of an "easy and natural" treatment for skin cancer, home remedies such as black salve can ...

  20. 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. PMID:22086728

  1. Genetics Home Reference: hereditary diffuse gastric cancer

    MedlinePlus

    ... JT, van Hillegersberg R, Dekker E, Oliveira C, Cats A, Hoogerbrugge N; Dutch Working Group on Hereditary ... JH, van Hillegersberg R, Ligtenberg M, Bleiker E, Cats A; Dutch Working Group on Hereditary Gastric Cancer. ...

  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. 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

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

    PubMed

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

    2005-12-01

    Due to a payment system based on Comprehensive Medical Evaluation has been adopted, both a shorter hospitalization and the use of home nursing care have been increasing. A good cooperation between hospital and home visiting nurses is desired in order to transfer continued nursing. Regarding a home nursing care service for the most terminal cancer patients, we conducted a survey of 459 home visiting nurses with twelve questions in five categories: (1) Before transferring to home care, (2) Right after the transfer to home care, (3) Patient in a stable period, (4) Time of near death and (5) Other (Requests to hospital nurses). The following issues became clearer in terms of how hospital and home visiting nurses should be cooperating with the handling of last stage terminal cancer patients: (1) A home visiting nurse should have a coordinating role with a hospital nurse when the patient is discharged from the hospital. (2) A participation of home visiting nurses on the coordination guidance at the time of a patient discharge is influenced by a manpower of the nursing station. (3) Even though home visiting nurses found a discrepancy between the hospital information and what patients and their families were getting from the hospital, home visiting nurses have learned through the job to clarify what patient and family needs were, and they responded accordingly. (4) A coordination between hospital and home visiting nurses was needed quite often when the patient's time has come to die at home. PMID:16422484

  5. 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.

  6. 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,

  7. Orphan symptoms in advanced cancer patients followed at home.

    PubMed

    Mercadante, Sebastiano; Porzio, Giampiero; Valle, Alessandro; Fusco, Flavio; Aielli, Federica; Adile, Claudio; Casuccio, Alessandra

    2013-12-01

    Orphan symptoms are rarely assessed, particularly at home. The aim of this multicenter prospective study was to assess the prevalence of these symptoms and eventual factors possibly associated in advanced cancer patients at admission of a home care program. A prospective study was performed at three home care programs in Italy. Patients' data were collected, including age, sex, diagnosis, and Karnofsky status. Possible contributing factors were analyzed; preexisting neurological diseases, cerebral metastases, hyperthermia, diabetes, a state of dehydration clinically evident and/or oliguria, possible biochemical parameters when available, data regarding recent chemotherapy, opioids and doses, use of neuroleptics, benzodiazepine or anticonvulsants, corticosteroids, anti-inflammatory, and antibiotics were collected. Myoclonus, hiccup, sweating, pruritus, and tenesmus, either rectal or vesical, were assessed, according to a preliminary definition, at time of home care program admission. Three hundred sixty-two patients were surveyed at the three home care programs. Globally, 48 patients presented one or more orphan symptoms in the period taken into consideration, and 7 patients presented more than 1 symptom. One patient presented occasional and diffuse myoclonus. Nineteen patients presented sweating, 13 patients presented pruritus, and 14 patients presented hiccup. Finally, nine patients presented rectal or vesical tenesmus. There was a significant correlation between sweating and transdermal fentanyl use (P = 0.044), fever (P = 0.001), hiccup (P < 0.0005), and vesical tenesmus (P = 0.028). Pruritus was not associated to any factor. Hiccup was associated with gender (males, P = 0.006) and sweating (P < 0.0005). Vesical tenesmus was associated with fever (P = 0.019) and sweating (P = 0.028). Although the symptoms examined have a low prevalence in advanced cancer patients admitted to home care, the distress for patients may be high and

  8. 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. PMID:19961057

  9. Problems faced by relatives caring for cancer patients at home.

    PubMed

    Tsigaroppoulos, Thomas; Mazaris, Evangelos; Chatzidarellis, Eleftherios; Skolarikos, Andreas; Varkarakis, Ioannis; Deliveliotis, Charalambos

    2009-02-01

    The care of patients suffering from advanced cancer is not limited in the hospital setting. It continues at home where the burden of care is borne by specific individuals. The aim of the present study was to survey and record the various problems faced by those who care for cancer patients at home. The study was conducted in our hospital during the summer of 2007. All participants completed, during a personal interview, a questionnaire which covered pathologic, social, psychological, spiritual/religious and financial problems. Seventy-six carers returned fully completed questionnaires. The most frequent problems reported were: anxiety regarding the patient's future (61.8%), troublesome symptoms such as pain (54%), increased economic burden-financial difficulty (51.3%), problems with patient's feeding (50%), unhappiness or depression (48,7%), emotional upset (47.4%), worsening of the patient's behaviour and personality (38.2%), difficulty of establishing a positive attitude regarding their current status (34.2%), transport to hospital (32.9%), assistance from the wider family circle (25%). Taking care of cancer patients at home creates several problems among carers. Many of them remain undetected. The acknowledgement and recognition of these problems by health-care professionals might contribute to finding solutions in order to assist the difficult task of these individuals. PMID:19187163

  10. [Choice of Expiration for Cancer Patients under Home Medical Care - Palliative Care Unit or Home].

    PubMed

    Okino, Takashi; Okagaki, Tetsuya; Nakamura, Hiromi; Okino, Akie

    2015-12-01

    Kohka Public Hospital(KPH)was rebuilt at a new place in April 2013. The Palliative Care Unit(PCU)was newly constructed during renovation. We examined the will and outcome of cancer patients, especially on expiration. A 123 patients died in 2014: 27 died at the PCU, and the remaining 7 at home. Of 27 patients, 20 were willing to die at the PCU, and one patient visited the hospital after judgment by the Visiting Nurse Center. Other 6 patients were admitted finally after their families experienced fatigue. Six of seven patients who died at home, showed a strong will to stay at home. We think that patients' will drives the clinical course, especially in their end-stage. In this context, the majority of the patients decided their terminal place based on their will. On the contrary, there were several cases whose requests were not fulfilled. To overcome the problem, we should discuss cancer patients' will to make a choice regarding death at the end-stage of their lives and the place of expiration in advance. We including the staff of social care and regional medical resources, should co-operate and share information on these patients to solve the problems. PMID:26809413

  11. Behavioral Development Profile. Manual I. Parent/Child Home Stimulation 'The Marshalltown Project'.

    ERIC Educational Resources Information Center

    Donahue, Michael J.; And Others

    Described is the Marshalltown Behavioral Development Profile, developed for handicapped and culturally deprived children in the 0-6 year range, and designed to facilitate individualized prescriptive teaching of preschool children within the home setting. The profile check list is arranged under three categories of behavior: communication, motor,…

  12. A Profile of the Newly-Admitted Nursing Home Resident.

    ERIC Educational Resources Information Center

    Erber, Joan T.; Dye, Carol J.

    1982-01-01

    Recently admitted nursing home residents received a battery of psychological tests and were rated on a number of behavioral indices. Results revealed the morale/anxiety dimension was independent of cognitive competency, internally controlled residents were rated high by others in behavioral competency, and self-rating scales measure something…

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. Molecular profiling of breast cancer: portraits but not physiognomy.

    PubMed

    Brenton, J D; Aparicio, S A; Caldas, C

    2001-01-01

    Breast cancers differ in response to treatment and may have a divergent clinical course despite having a similar histopathological appearance. New technology using DNA microarrays provides a systematic method to identify key markers for prognosis and treatment response by profiling thousands of genes expressed in a single cancer. Microarray profiling of 38 invasive breast cancers now confirms striking molecular differences between ductal carcinoma specimens and suggests a new classification for oestrogen-receptor negative breast cancer. Future approaches will need to include methods for high-throughput clinical validation and the ability to analyze microscopic samples. PMID:11250749

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

    SciTech Connect

    Chuang, J.; Cao, S.; Xian, Y.; Harris, B.; Mumford, J.

    1992-01-01

    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 micrometers) 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.

  19. 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.

  20. 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

  1. 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

  2. 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…

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

    PubMed

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

    2016-01-01

    Extracellular vesicles are cell-derived vesicles, which can transport various cargos out of cells. From their cell of origin, the content molecules (proteins, non-coding RNAs including miRNAs, DNA and others) can be delivered to neighboring or distant cells and as such extracellular vesicles can be regarded as vehicles of intercellular communication or "homing pigeons". Extracellular vesicle shuttling is able to actively modulate the tumor microenvironment and can partake in tumor dissemination. In various diseases, including cancer, levels of extracellular vesicle secretion are altered resulting in different amounts and/or profiles of detectable vesicular cargo molecules and these distinct content profiles are currently being evaluated as biomarkers. Apart from their potential as blood-derived containers of specific biomarkers, the transfer of extracellular vesicles to surrounding cells also appears to be involved in the propagation of phenotypic traits. These interesting properties have put extracellular vesicles into the focus of many recent studies.Here we review findings on the involvement of extracellular vesicles in transferring traits of cancer cells to their surroundings and briefly discuss new data on oncosomes, a larger type of vesicle. A pressing issue in cancer treatment is rapidly evolving resistance to many initially efficient drug therapies. Studies investigating the role of extracellular vesicles in this phenomenon together with a summary of the technical challenges that this field is still facing, are also presented. Finally, emerging areas of research such as the analysis of the lipid composition on extracellular vesicles and cutting-edge techniques to visualise the trafficking of extracellular vesicles are discussed. PMID:27282631

  4. Proteomic global profiling for cancer biomarker discovery.

    PubMed

    Faca, Vitor; Wang, Hong; Hanash, Samir

    2009-01-01

    The ultimate goal of cancer molecular diagnostics is the development of simple tests to predict cancer risk, detect cancer early, classify tumors, and monitor response to therapy. Proteomics is well suited for these tasks. However, there are substantial challenges that need to be met to identify the most informative markers using proteomics. Approaches for in-depth quantitative proteomic analysis based on isotopic labeling and protein fractionation are presented in this chapter. PMID:19241042

  5. Toxicogenetic profile and cancer risk in Lebanese.

    PubMed

    Dhaini, Hassan R; Kobeissi, Loulou

    2014-01-01

    An increasing number of genetic polymorphisms in drug-metabolizing enzymes (DME) were identified among different ethnic groups. Some of these polymorphisms are associated with an increased cancer risk, while others remain equivocal. However, there is sufficient evidence that these associations become significant in populations overexposed to environmental carcinogens. Hence, genetic differences in expression activity of both Phase I and Phase II enzymes may affect cancer risk in exposed populations. In Lebanon, there has been a marked rise in reported cancer incidence since the 1990s. There are also indicators of exposure to unusually high levels of environmental pollutants and carcinogens in the country. This review considers this high cancer incidence by exploring a potential gene-environment model based on available DME polymorphism prevalence, and their impact on bladder, colorectal, prostate, breast, and lung cancer in the Lebanese population. The examined DME include glutathione S-transferases (GST), N-acetyltransferases (NAT), and cytochromes P-450 (CYP). Data suggest that these DME influence bladder cancer risk in the Lebanese population. Evidence indicates that identification of a gene-environment interaction model may help in defining future research priorities and preventive cancer control strategies in this country, particularly for breast and lung cancer. PMID:24627976

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

    PubMed Central

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

    2016-01-01

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

  7. 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. PMID:26422541

  8. Genomic Profiling in Luminal Breast Cancer

    PubMed Central

    Gluz, Oleg; Hofmann, Daniel; Würstlein, Rachel; Liedtke, Cornelia; Nitz, Ulrike; Harbeck, Nadia

    2013-01-01

    Summary The developments in gene expression analysis have made it possible to sub-classify hormone receptor-positive (luminal) breast cancer in different prognostic subgroups. This sub-classification is currently used in clinical routine as prognostic signature (e.g. 21-gene Onoctype DX®, 70-gene Mammaprint®). As yet, the optimal method for sub-classification has not been defined. Moreover, there is no evidence from prospective trials. This review explores widely used genomic signatures in luminal breast cancer, making a critical appraisal of evidence from retrospective/prospective trials. It is based on systematic literature search performed using Medline (accessed September 2013) and abstracts presented at the Annual Meeting of American Society of Clinical Oncology and San Antonio Breast Cancer Symposium. PMID:24550749

  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. Profile of olaparib in the treatment of advanced ovarian cancer

    PubMed Central

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

    2016-01-01

    Olaparib is a poly(ADP-ribose) polymerase inhibitor that received accelerated approval from the US Food and Drug Administration as monotherapy for patients with germline BRCA mutations and ovarian cancer treated with three or more prior lines of chemotherapy. This article summarizes the mechanism of poly(ADP-ribose) polymerase inhibition, therapeutic profile and uses of olaparib, and current and ongoing literature pertaining to olaparib in advanced ovarian cancer. PMID:27186080

  11. Gene expression profiling analysis of ovarian cancer

    PubMed Central

    YIN, JI-GANG; LIU, XIAN-YING; WANG, BIN; WANG, DAN-YANG; WEI, MAN; FANG, HUA; XIANG, MEI

    2016-01-01

    As a gynecological oncology, ovarian cancer has high incidence and mortality. To study the mechanisms of ovarian cancer, the present study analyzed the GSE37582 microarray. GSE37582 was downloaded from Gene Expression Omnibus and included data from 74 ovarian cancer cases and 47 healthy controls. The differentially-expressed genes (DEGs) were screened using linear models for microarray data package in R and were further screened for functional annotation. Next, Gene Ontology and pathway enrichment analysis of the DEGs was conducted. The interaction associations of the proteins encoded by the DEGs were searched using the Search Tool for the Retrieval of Interacting Genes, and the protein-protein interaction (PPI) network was visualized by Cytoscape. Moreover, module analysis of the PPI network was performed using the BioNet analysis tool in R. A total of 284 DEGs were screened, consisting of 145 upregulated genes and 139 downregulated genes. In particular, downregulated FBJ murine osteosarcoma viral oncogene homolog (FOS) was an oncogene, while downregulated cyclin-dependent kinase inhibitor 1A (CDKN1A) was a tumor suppressor gene and upregulated cluster of differentiation 44 (CD44) was classed as an ‘other’ gene. The enriched functions included collagen catabolic process, stress-activated mitogen-activated protein kinases cascade and insulin receptor signaling pathway. Meanwhile, FOS (degree, 15), CD44 (degree, 9), B-cell CLL/lymphoma 2 (BCL2; degree, 7), CDKN1A (degree, 7) and matrix metallopeptidase 3 (MMP3; degree, 6) had higher connectivity degrees in the PPI network for the DEGs. These genes may be involved in ovarian cancer by interacting with other genes in the module of the PPI network (e.g., BCL2-FOS, BCL2-CDKN1A, FOS-CDKN1A, FOS-CD44, MMP3-MMP7 and MMP7-CD44). Overall, BCL2, FOS, CDKN1A, CD44, MMP3 and MMP7 may be correlated with ovarian cancer. PMID:27347159

  12. Prediction of individualized therapeutic vulnerabilities in cancer from genomic profiles

    PubMed Central

    Aksoy, Bülent Arman; Demir, Emek; Babur, Özgün; Wang, Weiqing; Jing, Xiaohong; Schultz, Nikolaus; Sander, Chris

    2014-01-01

    Motivation: Somatic homozygous deletions of chromosomal regions in cancer, while not necessarily oncogenic, may lead to therapeutic vulnerabilities specific to cancer cells compared with normal cells. A recently reported example is the loss of one of the two isoenzymes in glioblastoma cancer cells such that the use of a specific inhibitor selectively inhibited growth of the cancer cells, which had become fully dependent on the second isoenzyme. We have now made use of the unprecedented conjunction of large-scale cancer genomics profiling of tumor samples in The Cancer Genome Atlas (TCGA) and of tumor-derived cell lines in the Cancer Cell Line Encyclopedia, as well as the availability of integrated pathway information systems, such as Pathway Commons, to systematically search for a comprehensive set of such epistatic vulnerabilities. Results: Based on homozygous deletions affecting metabolic enzymes in 16 TCGA cancer studies and 972 cancer cell lines, we identified 4104 candidate metabolic vulnerabilities present in 1019 tumor samples and 482 cell lines. Up to 44% of these vulnerabilities can be targeted with at least one Food and Drug Administration-approved drug. We suggest focused experiments to test these vulnerabilities and clinical trials based on personalized genomic profiles of those that pass preclinical filters. We conclude that genomic profiling will in the future provide a promising basis for network pharmacology of epistatic vulnerabilities as a promising therapeutic strategy. Availability and implementation: A web-based tool for exploring all vulnerabilities and their details is available at http://cbio.mskcc.org/cancergenomics/statius/ along with supplemental data files. Contact: statius@cbio.mskcc.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:24665131

  13. Gene Expression Profiling of Gastric Cancer

    PubMed Central

    Marimuthu, Arivusudar; Jacob, Harrys K.C.; Jakharia, Aniruddha; Subbannayya, Yashwanth; Keerthikumar, Shivakumar; Kashyap, Manoj Kumar; Goel, Renu; Balakrishnan, Lavanya; Dwivedi, Sutopa; Pathare, Swapnali; Dikshit, Jyoti Bajpai; Maharudraiah, Jagadeesha; Singh, Sujay; Sameer Kumar, Ghantasala S; Vijayakumar, M.; Veerendra Kumar, Kariyanakatte Veeraiah; Premalatha, Chennagiri Shrinivasamurthy; Tata, Pramila; Hariharan, Ramesh; Roa, Juan Carlos; Prasad, T.S.K; Chaerkady, Raghothama; Kumar, Rekha Vijay; Pandey, Akhilesh

    2015-01-01

    Gastric cancer is the second leading cause of cancer death worldwide, both in men and women. A genomewide gene expression analysis was carried out to identify differentially expressed genes in gastric adenocarcinoma tissues as compared to adjacent normal tissues. We used Agilent’s whole human genome oligonucleotide microarray platform representing ~41,000 genes to carry out gene expression analysis. Two-color microarray analysis was employed to directly compare the expression of genes between tumor and normal tissues. Through this approach, we identified several previously known candidate genes along with a number of novel candidate genes in gastric cancer. Testican-1 (SPOCK1) was one of the novel molecules that was 10-fold upregulated in tumors. Using tissue microarrays, we validated the expression of testican-1 by immunohistochemical staining. It was overexpressed in 56% (160/282) of the cases tested. Pathway analysis led to the identification of several networks in which SPOCK1 was among the topmost networks of interacting genes. By gene enrichment analysis, we identified several genes involved in cell adhesion and cell proliferation to be significantly upregulated while those corresponding to metabolic pathways were significantly downregulated. The differentially expressed genes identified in this study are candidate biomarkers for gastric adenoacarcinoma. PMID:27030788

  14. The Profile and Incidence of Cancer in Down Syndrome

    ERIC Educational Resources Information Center

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

    2007-01-01

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

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

    ERIC Educational Resources Information Center

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

    2004-01-01

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

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

    PubMed Central

    Zardavas, Dimitrios; Piccart-Gebhart, Martine

    2016-01-01

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

  17. Mutation profiling in gallbladder cancer in Indian population

    PubMed Central

    Kumari, Niraj; Corless, Christopher L.; Warrick, Andrea; Beadling, Carol; Nelson, Dylan; Neff, Tanay; Krishnani, Narendra; Kapoor, Vinay Kumar

    2015-01-01

    Aim Gallbladder cancer is an aggressive malignancy usually diagnosed at late stage. The molecular genetics of this cancer is heterogeneous and not well established. Mutation profiling of gallbladder cancer was performed through massarray technology with an aim to identify molecular markers involved in the tumor pathogenesis that can be helpful as markers for early diagnosis and targets for therapy. Materials and Methods Forty nine cases of gallbladder cancer were screened through Sequenom Massarray technology for 390 mutations across 30 genes in formalin fixed paraffin embedded archived tissues and the results of mutation profiling was correlated with tumor characteristics. Mutations were observed in 9 of 49 cases across four genes - TP53 (four cases), CTNNB1 (two cases), PIK3CA (two cases), and KRAS (one case). Six of these cases were well differentiated but of eight of them belonged to stage II to IV disease. Six cases had associated gallstones. Conclusion The mutation frequency found in gallbladder cancer is comparable to the data available in literature. Identification of PIK3CA and KRAS mutations would help in formulating more efficacious targeted approach for management. Studies with large number of cases would help in exploring more targets and better classification of these cancers at genetic level. PMID:24739824

  18. Transcription profiles of non-immortalized breast cancer cell lines

    PubMed Central

    Fernandez-Cobo, Mariana; Holland, James F; Pogo, Beatriz GT

    2006-01-01

    Background Searches for differentially expressed genes in tumours have made extensive use of array technology. Most samples have been obtained from tumour biopsies or from established tumour-derived cell lines. Here we compare cultures of non-immortalized breast cancer cells, normal non-immortalized breast cells and immortalized normal and breast cancer cells to identify which elements of a defined set of well-known cancer-related genes are differentially expressed. Methods Cultures of cells from pleural effusions or ascitic fluids from breast cancer patients (MSSMs) were used in addition to commercially-available normal breast epithelial cells (HMECs), established breast cancer cell lines (T-est) and established normal breast cells (N-est). The Atlas Human Cancer 1.2 cDNA expression array was employed. The data obtained were analysed using widely-available statistical and clustering software and further validated through real-time PCR. Results According to Significance Analysis of Microarray (SAM) and AtlasImage software, 48 genes differed at least 2-fold in adjusted intensities between HMECs and MSSMs (p < 0.01). Some of these genes have already been directly linked with breast cancer, metastasis and malignant progression, whilst others encode receptors linked to signal transduction pathways or are otherwise related to cell proliferation. Fifty genes showed at least a 2.5-fold difference between MSSMs and T-est cells according to AtlasImage, 2-fold according to SAM. Most of these classified as genes related to metabolism and cell communication. Conclusion The expression profiles of 1176 genes were determined in finite life-span cultures of metastatic breast cancer cells and of normal breast cells. Significant differences were detected between the finite life-span breast cancer cell cultures and the established breast cancer cell lines. These data suggest caution in extrapolating information from established lines for application to clinical cancer research. PMID

  19. 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

  20. What can digital transcript profiling reveal about human cancers?

    PubMed

    Cerutti, J M; Riggins, G J; de Souza, S J

    2003-08-01

    Important biological and clinical features of malignancy are reflected in its transcript pattern. Recent advances in gene expression technology and informatics have provided a powerful new means to obtain and interpret these expression patterns. A comprehensive approach to expression profiling is serial analysis of gene expression (SAGE), which provides digital information on transcript levels. SAGE works by counting transcripts and storing these digital values electronically, providing absolute gene expression levels that make historical comparisons possible. SAGE produces a comprehensive profile of gene expression and can be used to search for candidate tumor markers or antigens in a limited number of samples. The Cancer Genome Anatomy Project has created a SAGE database of human gene expression levels for many different tumors and normal reference tissues and provides online tools for viewing, comparing, and downloading expression profiles. Digital expression profiling using SAGE and informatics have been useful for identifying genes that have a role in tumor invasion and other aspects of tumor progression. PMID:12886451

  1. The At-Home Multidisciplinary Rehabilitation Team: A New Trend in Cancer Rehabilitation.

    ERIC Educational Resources Information Center

    Bluhm, Harry P.; And Others

    1979-01-01

    The implementation of a multidisciplinary rehabilitation team in providing rehabilitative services to discharged cancer patients in an in-home situation is outlined in this article. The characteristics of effective team coordinators, their functions, the nature of their services, and evaluation results are discussed. (Author)

  2. 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

    2016-01-01

    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. PMID:26602695

  3. 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.

  4. Cancer profile of Larkana, Pakistan (2000-2002).

    PubMed

    Bhurgri, Yasmin; Pervez, Shahid; Kayani, Naila; Bhurgri, Asif; Usman, Ahmed; Bashir, Imtiaz; Ahmed, Rashida; Hasan, Sheema H; Khurshid, Mohd H

    2006-01-01

    This present study was conducted with the objective of providing the cancer profile of Larkana, the fourth largest city of Sindh, Province. The study included two sets of patients. The first set included the incident cancer cases, residents of Larkana, who reached Karachi for diagnosis or treatment. The second set consisted of the incident cancer cases registered at the Aga Khan University (AKU) Pathology collection points at Larkana during 1st January 2000 to 31st December 2002. The age-standardized rates (ASR) for cancer (all sites) were 134.2/100,000 in males and 110.3/100,000 in females. The most common malignancies in males were lymphoma, oral cavity, prostate, liver, and urinary bladder. Cancers in females were breast, oral cavity, lymphoma, skin and thyroid. Tobacco-associated cancers accounted for approximately 35.0% of the tumors in males and 18.6% in females. The gender ratio was 1.5, the mean age of cancer all sites was 45.5 years (95% CI 34.6; 56.4) in males and 42.9 years (95% CI 33.6; 52.2) in females. This is the first attempt to determine the cancer incidence pattern of Larkana and should serve as a guideline for estimation of the cancer burden of Pakistan and the cancer control program of the country. The data must be interpreted with care, as they are largely pathology-based with approximately 15-30% population-wise under-registration. However, the chances of selective collection bias were minimized as the AKU pathology specimens were collected from 2 centers within the city, Each collection centre provided diagnostic service to several health centres giving wide population coverage, thus ensuring adequate sampling from the entire city. PMID:17250420

  5. A distinct molecular profile associated with mucinous epithelial ovarian cancer

    PubMed Central

    Heinzelmann-Schwarz, V A; Gardiner-Garden, M; Henshall, S M; Scurry, J P; Scolyer, R A; Smith, A N; Bali, A; Bergh, P Vanden; Baron-Hay, S; Scott, C; Fink, D; Hacker, N F; Sutherland, R L; O'Brien, P M

    2006-01-01

    Mucinous epithelial ovarian cancers (MOC) are clinically and morphologically distinct from the other histological subtypes of ovarian cancer. To determine the genetic basis of MOC and to identify potential tumour markers, gene expression profiling of 49 primary ovarian cancers of different histological subtypes was performed using a customised oligonucleotide microarray containing >59 000 probesets. The results show that MOC express a genetic profile that both differs and overlaps with other subtypes of epithelial ovarian cancer. Concordant with its histological phenotype, MOC express genes characteristic of mucinous carcinomas of varying epithelial origin, including intestinal carcinomas. Differences in gene expression between MOC and other histological subtypes of ovarian cancer were confirmed by RT–PCR and/or immunohistochemistry. In particular, galectin 4 (LGALS4) was highly and specifically expressed in MOC, but expressed at lower levels in benign mucinous cysts and borderline (atypical proliferative) tumours, supporting a malignant progression model of MOC. Hence LGALS4 may have application as an early and differential diagnostic marker of MOC. PMID:16508639

  6. 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…

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

    PubMed Central

    2014-01-01

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

  8. 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

  9. Metabolic profiling of breast cancer: Differences in central metabolism between subtypes of breast cancer cell lines.

    PubMed

    Willmann, Lucas; Schlimpert, Manuel; Halbach, Sebastian; Erbes, Thalia; Stickeler, Elmar; Kammerer, Bernd

    2015-09-01

    Although the concept of aerobic glycolysis in cancer was already reported in the 1930s by Otto Warburg, the understanding of metabolic pathways remains challenging especially due to the heterogeneity of cancer. In consideration of four different time points (1, 2, 4, and 7 days of incubation), GC-MS profiling of metabolites was performed on cell extracts and supernatants of breast cancer cell lines (MDA-MB-231, -453, BT-474) with different sub classification and the breast epithelial cell line MCF-10A. To the exclusion of trypsinization, direct methanolic extraction, cell scraping and cell disruption was executed to obtain central metabolites. Major differences in biochemical pathways have been observed in the breast cancer cell lines compared to the breast epithelial cell line, as well as between the breast cancer cell lines themselves. Characteristics of breast cancer subtypes could be correlated to their individual metabolic profiles. PLS-DA revealed the discrimination of breast cancer cell lines from MCF-10A based on elevated amino acid levels. The observed metabolic signatures have great potential as biomarker for breast cancer as well as an improved understanding of subtype specific phenomenons of breast cancer. PMID:26218769

  10. 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. PMID:22957961

  11. Molecular profiling of breast cancer: transcriptomic studies and beyond.

    PubMed

    Culhane, A C; Howlin, J

    2007-12-01

    Utilisation of 'omics' technologies, in particular gene expression profiling, has increased dramatically in recent years. In basic research, high-throughput profiling applications are increasingly used and may now even be considered standard research tools. In the clinic, there is a need for better and more accurate diagnosis, prognosis and treatment response indicators. As such, clinicians have looked to omics technologies for potential biomarkers. These prediction profiling studies have in turn attracted the attention of basic researchers eager to uncover biological mechanisms underlying clinically useful signatures. Here we highlight some of the seminal work establishing the arrival of the omics, in particular transcriptomics, in breast cancer research and discuss a sample of the most current applications. We also discuss the challenges of data analysis and integrated data analysis with emphasis on utilising the current publicly available gene expression datasets. (Part of a Multi-author Review). PMID:17957338

  12. Home-based Exercise among Cancer Survivors: Adherence and its Predictors

    PubMed Central

    Pinto, Bernardine M.; Rabin, Carolyn; Dunsiger, Shira

    2010-01-01

    Objective Evidence of the benefits of exercise for those treated for cancer has led to several exercise interventions for this population. Some have questioned whether cancer patients offered a home-based intervention adhere to the exercise prescribed. Method We examined exercise adherence in a randomized controlled trial of a 12-week, home-based exercise trial for breast cancer patients. Three adherence outcomes were examined: minutes of exercise participation during each week of the intervention, number of steps taken during planned exercise during each intervention week, and whether the participant met her weekly exercise goal. Predictors of adherence (e.g., demographic and medical variables, Transtheoretical Model variables, history of exercise) were examined. Results Findings indicate that participants significantly increased their minutes of exercise and steps taken during planned exercise from the first to the last week of the intervention. The percentage of participants achieving exercise goals was highest in the first few weeks of the intervention. Exercise self-efficacy significantly predicted each adherence outcome. Baseline PA predicted mean exercise session steps over the 12 weeks. Conclusion Adherence to a home-based exercise intervention for breast cancer patients changes over time and may be related to baseline levels of self-efficacy for exercise. PMID:19242921

  13. 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:…

  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. Genetic risk profiles for cancer susceptibility and therapy response.

    PubMed

    Bartsch, Helmut; Dally, Heike; Popanda, Odilia; Risch, Angela; Schmezer, Peter

    2007-01-01

    Cells in the body are permanently attacked by DNA-reactive species, both from intracellular and environmental sources. Inherited and acquired deficiencies in host defense mechanisms against DNA damage (metabolic and DNA repair enzymes) can modify cancer susceptibility as well as therapy response. Genetic profiles should help to identify high-risk individuals who subsequently can be enrolled in preventive measures or treated by tailored therapy regimens. Some of our attempts to define such risk profiles are presented. Cancer susceptibility: Single nucleotide polymorphisms (SNPs) in metabolic and repair genes were investigated in a hospital-based lung cancer case-control study. When evaluating the risk associated with different genotypes for N-acetyltransferases (Wikman et al. 2001) and glutathione-S-transferases (Risch et al. 2001), it is mandatory to distinguish between the three major histological subtypes of lung tumors. A promoter polymorphism of the myeloperoxidase gene MPO was shown to decrease lung cancer susceptibility mainly in small cell lung cancer (SCLC) (Dally et al. 2002). The CYP3A4*1B allele was also linked to an increased SCLC risk and in smoking women increased the risk of lung cancer eightfold (Dally et al. 2003b). Polymorphisms in DNA repair genes were shown to modulate lung cancer risk in smokers, and reduced DNA repair capacity elevated the disease risk (Rajaee-Behbahani et al. 2001). Investigations of several DNA repair gene variants revealed that lung cancer risk was only moderately affected by a single variant but was enhanced up to approximately threefold by specific risk allele combinations (Popanda et al. 2004). Therapy response: Inter-individual differences in therapy response are consistently observed with cancer chemotherapeutic agents. Initial results from ongoing studies showed that certain polymorphisms in drug transporter genes (ABCB1) differentially affect response outcome in histological subgroups of lung cancer. Stronger

  16. 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. PMID:26573639

  17. Gendered Processes in Hospice Palliative Home Care for Seniors With Cancer and Their Family Caregivers.

    PubMed

    Sutherland, Nisha; Ward-Griffin, Catherine; McWilliam, Carol; Stajduhar, Kelli

    2016-06-01

    There has been limited investigation into the processes that shape gender (in)equities in hospice palliative home care. As part of a larger critical ethnographic study, we examined how and why gender relations occur in this context. Using a critical feminist lens, we conducted in-depth interviews with clients living with terminal cancer, their family caregivers and primary nurses; observations of agency home visits; and review of institutional documents. A gender-based analysis revealed that gender enactments of Regulating Gender Relations were legitimized through ideological processes of Normalizing Gender Relations and Equalizing Gender Relations (Re)produced through institutional discourses of individualism and egalitarianism, these gendered processes both advantaged and disadvantaged men and women in hospice palliative home care. Findings suggest that to promote equity, health care providers and policy makers must attend to gender as a prevalent social determinant of health and health care. Implications for policy, practice, education, and research are discussed. PMID:26489710

  18. Genomic Interaction Profiles in Breast Cancer Reveal Altered Chromatin Architecture

    PubMed Central

    Zeitz, Michael J.; Ay, Ferhat; Heidmann, Julia D.; Lerner, Paula L.

    2013-01-01

    Gene transcription can be regulated by remote enhancer regions through chromosome looping either in cis or in trans. Cancer cells are characterized by wholesale changes in long-range gene interactions, but the role that these long-range interactions play in cancer progression and metastasis is not well understood. In this study, we used IGFBP3, a gene involved in breast cancer pathogenesis, as bait in a 4C-seq experiment comparing normal breast cells (HMEC) with two breast cancer cell lines (MCF7, an ER positive cell line, and MDA-MB-231, a triple negative cell line). The IGFBP3 long-range interaction profile was substantially altered in breast cancer. Many interactions seen in normal breast cells are lost and novel interactions appear in cancer lines. We found that in HMEC, the breast carcinoma amplified sequence gene family (BCAS) 1–4 were among the top 10 most significantly enriched regions of interaction with IGFBP3. 3D-FISH analysis indicated that the translocation-prone BCAS genes, which are located on chromosomes 1, 17, and 20, are in close physical proximity with IGFBP3 and each other in normal breast cells. We also found that epidermal growth factor receptor (EGFR), a gene implicated in tumorigenesis, interacts significantly with IGFBP3 and that this interaction may play a role in their regulation. Breakpoint analysis suggests that when an IGFBP3 interacting region undergoes a translocation an additional interaction detectable by 4C is gained. Overall, our data from multiple lines of evidence suggest an important role for long-range chromosomal interactions in the pathogenesis of cancer. PMID:24019942

  19. Profile of thyroid hormones in breast cancer patients.

    PubMed

    Saraiva, P P; Figueiredo, N B; Padovani, C R; Brentani, M M; Nogueira, C R

    2005-05-01

    Estrogen involvement in breast cancer has been established; however, the association between breast cancer and thyroid diseases is controversial. Estrogen-like effects of thyroid hormone on breast cancer cell growth in culture have been reported. The objective of the present study was to determine the profile of thyroid hormones in breast cancer patients. Serum aliquots from 26 patients with breast cancer ranging in age from 30 to 85 years and age-matched normal controls (N = 22) were analyzed for free triiodothyronine (T3F), free thyroxine (T4F), thyroid-stimulating hormone (TSH), antiperoxidase antibody (TPO), and estradiol (E2). Estrogen receptor ss (ERss) was determined in tumor tissues by immunohistochemistry. Thyroid disease incidence was higher in patients than in controls (58 vs 18%, P < 0.05). Subclinical hyperthyroidism was the most frequent disorder in patients (31%); hypothyroidism (8%) and positive anti-TPO antibodies (19%) were also found. Subclinical hypothyroidism was the only dysfunction (18%) found in controls. Hyperthyroidism was associated with postmenopausal patients, as shown by significantly higher mean T3 and T4 values and lower TSH levels in this group of breast cancer patients than in controls. The majority of positive ERss tumors were clustered in the postmenopausal patients and all cases presenting subclinical hyperthyroidism in this subgroup concomitantly exhibited Erss-positive tumors. Subclinical hyperthyroidism was present in only one of 6 premenopausal patients. We show here that postmenopausal breast cancer patients have a significantly increased thyroid hormone/E2 ratio (P < 0.05), suggesting a possible tumor growth-promoting effect caused by this misbalance. PMID:15917958

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

    PubMed

    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

  1. 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

  2. Biopathological profile of multiple synchronous homolateral and bilateral breast cancers.

    PubMed

    Cavaliere, Antonio; Bellezza, Guido; Scheibel, Massimo; Vitali, Rino; Sidoni, Angelo

    2004-01-01

    It still needs to be verified whether multiple syncronous homolateral and bilateral breast cancers represent intramammary spread of a single tumor or two or more separate neoplastic events. To clarify this problem, we studied the biopathological profile of 46 homolateral and 20 bilateral cases. The cancers were always surgically removed and processed at the same time. The expression of estrogen receptors (ER), progesterone receptors (PR), MIB 1, p53, and c-erbB-2 was determined. Computer-assisted image analysis (CAS 200) was used to evaluate ER, PR, MIB 1, and p53. The histological concordance was 95.6% in homolateral and 50% in bilateral cases. The immunophenotype profile of multiple homolateral neoplasms showed a concordance between 93.47% for ER and 78.26% for p53. The results were statistically significant for all parameters except for p53. In bilateral cancers, there was a significant statistical concordance for ER. These data strongly suggest that both mechanisms may exert an influence and, in particular, that in the majority of homolateral carcinomas, there may be intramammary spread of tumor cells. In multiple bilateral tumors, however, the great diversity of the histological aspects and the differences in the immunophenotype pattern suggest that the vast majority of these may constitute independent multiple events. PMID:15157045

  3. Feasibility Study: Home Telemonitoring for Patients With Lung Cancer in a Mountainous Rural Area

    PubMed Central

    Petitte, Trisha M.; Narsavage, Georgia L.; Chen, Yea-Jyh; Coole, Charles; Forth, Tara; Frick, Kevin D.

    2015-01-01

    Purpose/Objectives To explore the feasibility of rural home telemonitoring for patients with lung cancer. Design Exploratory, descriptive, observational. Setting Patient homes within a 75-mile radius of the study hospital in West Virginia. Sample 10 patients hospitalized with lung cancer as a primary or secondary-related diagnosis. Methods Data included referral and demographics, chart reviews, and clinical data collected using a HomMed telemonitor. Five patients received usual care after discharge; five had telemonitors set up at home for 14 days with daily phone calls for nurse coaching; mid- and end-study data were collected by phone and in homes through two months. Main Research Variables Enrollment and retention characteristics, physiologic (e.g., temperature, pulse, blood pressure, weight, O2 saturation) and 10 symptom datapoints, patient and family telemonitor satisfaction. Findings Of 45 referred patients, only 10 consented; 1 of 5 usual care and 3 of 5 monitored patients completed the entire study. Telemonitored data transmission was feasible in rural areas with high satisfaction; symptom data and physiologic data were inconsistent but characteristic of lung cancer. Conclusions Challenges included environment, culture, technology, and overall enrollment and retention. Physiologic and symptom changes were important data for nurse coaching on risks, symptom management, and clinician contact. Implications for Nursing Enrollment and retention in cancer research warrants additional study. Daily monitoring is feasible and important in risk assessment, but length of time to monitor signs and symptoms, which changed rapidly, is unclear. Symptom changes were useful as proxy indicators for physiologic changes, so risk outcomes may be assessable by phone for patient self-management coaching by nurses. PMID:24578075

  4. In-Home Coal and Wood Use and Lung Cancer Risk: A Pooled Analysis of the International Lung Cancer Consortium

    PubMed Central

    Hosgood, H. Dean; Boffetta, Paolo; Greenland, Sander; Lee, Yuan-Chin Amy; McLaughlin, John; Seow, Adeline; Duell, Eric J.; Andrew, Angeline S.; Zaridze, David; Szeszenia-Dabrowska, Neonila; Rudnai, Peter; Lissowska, Jolanta; Fabiánová, Eleonóra; Mates, Dana; Bencko, Vladimir; Foretova, Lenka; Janout, Vladimir; Morgenstern, Hal; Rothman, Nathaniel; Hung, Rayjean J.; Brennan, Paul; Lan, Qing

    2010-01-01

    Background Domestic fuel combustion from cooking and heating is an important public health issue because roughly 3 billion people are exposed worldwide. Recently, the International Agency for Research on Cancer classified indoor emissions from household coal combustion as a human carcinogen (group 1) and from biomass fuel (primarily wood) as a probable human carcinogen (group 2A). Objectives We pooled seven studies from the International Lung Cancer Consortium (5,105 cases and 6,535 controls) to provide further epidemiological evaluation of the association between in-home solid-fuel use, particularly wood, and lung cancer risk. Methods Using questionnaire data, we classified subjects as predominant solid-fuel users (e.g., coal, wood) or nonsolid-fuel users (e.g., oil, gas, electricity). Unconditional logistic regression was used to estimate the odds ratios (ORs) and to compute 95% confidence intervals (CIs), adjusting for age, sex, education, smoking status, race/ethnicity, and study center. Results Compared with nonsolid-fuel users, predominant coal users (OR = 1.64; 95% CI, 1.49–1.81), particularly coal users in Asia (OR = 4.93; 95% CI, 3.73–6.52), and predominant wood users in North American and European countries (OR = 1.21; 95% CI, 1.06–1.38) experienced higher risk of lung cancer. The results were similar in never-smoking women and other subgroups. Conclusions Our results are consistent with previous observations pertaining to in-home coal use and lung cancer risk, support the hypothesis of a carcinogenic potential of in-home wood use, and point to the need for more detailed study of factors affecting these associations. PMID:20846923

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

    SciTech Connect

    none,

    2014-11-01

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

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

    PubMed

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

    2012-06-01

    Home blood transfusion may be an interesting alternative to hospital transfusion, especially when given with curative or palliative intent or for terminal care in advanced-stage cancer patients. However, there is limited information about patients' attitude toward this type of care. The purpose of this study was to measure French cancer patients' willingness to pay (WTP) for home blood transfusion and to analyze determinants of their choice. A contingent valuation survey was administered to 139 patients receiving transfusions in the framework of a regional home care network or in the hospital outpatient department. Participation was high (90%). Most patients (65%) had received home care, including 43% blood transfusions. Just under half of the patients gave a zero WTP, among which we identified 8 protest bidders. The median WTP for home blood transfusion was 26.5 per patient. In multivariate analysis, long home-hospital distance, poor quality of life, and previous experience of home care were identified as important factors in determining how much more patients would be willing to pay for transfusion at home. These results demonstrate the benefits of developing domiciliary services to improve patient well-being, notably for the weakest among them. The significant impact of previous home care experience on WTP is probably related to the strong involvement of physicians from the blood center and to their active contribution to a high-level homecare network. Some of our findings could be useful for policy decision-making regarding home care. PMID:21660563

  7. 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. PMID:25752741

  8. Rural Alberta Home-Based Businesses: A Profile of Workshop Participants.

    ERIC Educational Resources Information Center

    Capjack, M. Linda; Fetterman, Nelma I.

    1992-01-01

    Of 252 rural Alberta attendees of home-based business workshops, 60 were in business. Of these, 65 percent produced sewing, textile, or food-related products; 73 percent contributed less than 5 percent of family income; 72 percent worked at home because a hobby became profitable; and the majority were married women over 40. (SK)

  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. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. Global DNA methylation profiling technologies and the ovarian cancer methylome.

    PubMed

    Tang, Jessica; Fang, Fang; Miller, Dave F; Pilrose, Jay M; Matei, Daniela; Huang, Tim Hui-Ming; Nephew, Kenneth P

    2015-01-01

    Cytosine methylation in DNA constitutes an important epigenetic layer of transcriptional and regulatory control in many eukaryotes. Profiling DNA methylation across the genome is critical to understanding the influence of epigenetics in normal biology and disease, such as cancer. Genome-wide analyses such as arrays and next-generation sequencing (NGS) technologies have been used to assess large fractions of the methylome at a single-base-pair resolution. However, the range of DNA methylation profiling techniques can make selecting the appropriate protocol a challenge. This chapter discusses the advantages and disadvantages of various methylome detection approaches to assess which is appropriate for the question at hand. Here, we focus on four prominent genome-wide approaches: whole-genome bisulfite sequencing (WGBS); methyl-binding domain capture sequencing (MBDCap-Seq); reduced-representation-bisulfite-sequencing (RRBS); and Infinium Methylation450 BeadChips (450 K, Illumina). We discuss some of the requirements, merits, and challenges that should be considered when choosing a methylome technology to ensure that it will be informative. In addition, we show how genome-wide methylation detection arrays and high-throughput sequencing have provided immense insight into ovarian cancer-specific methylation signatures that may serve as diagnostic biomarkers or predict patient response to epigenetic therapy. PMID:25421685

  16. Molecular profiling of patient-derived breast cancer xenografts

    PubMed Central

    2012-01-01

    Introduction Identification of new therapeutic agents for breast cancer (BC) requires preclinical models that reproduce the molecular characteristics of their respective clinical tumors. In this work, we analyzed the genomic and gene expression profiles of human BC xenografts and the corresponding patient tumors. Methods Eighteen BC xenografts were obtained by grafting tumor fragments from patients into Swiss nude mice. Molecular characterization of patient tumors and xenografts was performed by DNA copy number analysis and gene expression analysis using Affymetrix Microarrays. Results Comparison analysis showed that 14/18 pairs of tumors shared more than 56% of copy number alterations (CNA). Unsupervised hierarchical clustering analysis showed that 16/18 pairs segregated together, confirming the similarity between tumor pairs. Analysis of recurrent CNA changes between patient tumors and xenografts showed losses in 176 chromosomal regions and gains in 202 chromosomal regions. Gene expression profile analysis showed that less than 5% of genes had recurrent variations between patient tumors and their respective xenografts; these genes largely corresponded to human stromal compartment genes. Finally, analysis of different passages of the same tumor showed that sequential mouse-to-mouse tumor grafts did not affect genomic rearrangements or gene expression profiles, suggesting genetic stability of these models over time. Conclusions This panel of human BC xenografts maintains the overall genomic and gene expression profile of the corresponding patient tumors and remains stable throughout sequential in vivo generations. The observed genomic profile and gene expression differences appear to be due to the loss of human stromal genes. These xenografts, therefore, represent a validated model for preclinical investigation of new therapeutic agents. PMID:22247967

  17. 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.

  18. [Euthanasia: refusal requires alternatives. The home hospital model could be a solution for some cancer patients].

    PubMed

    Tanneberger, S

    1995-04-01

    Maybe more important than an emotional debate on "pro and con" of euthanasia is search of alternatives for all who would request for physician-assisted suicide. Obviously it is not easy to find such alternative approaches. However only these justify a position "contra euthanasia". As one alternative Franco Pannuti introduced 1985 the concept of Eubiosia. Eubiosia, what means, the set of qualities that give life dignity, was proposed as a fundamental right of all patients. And dying in dignity as part of life in dignity excludes euthanasia. In the same way as respecting beginning life we have to respect ending life. A possible approach to guarantee Eubiosia for cancer patients is the hospital at home. A hospital at home is a part of the health care system having his own structural and organisational characteristics. It guarantees for a certain group of patients clinical level of care at the comfort of their own homes. The evaluation of 10,236 patients admitted in the Bologna home hospital, show that a majority of patients favour this care model which additional can have economical advantages. PMID:7539192

  19. 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

  20. 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

  1. [A study of "sudden death" in end-stage cancer patients receiving home care].

    PubMed

    Suzuki, Michiaki; Ishimaki, Shizuyo; Yamazaki, Fumio

    2013-12-01

    We retrospectively examined the actual status and management of sudden changes in end-stage cancer patients receiving home care. We defined "sudden death" as an incident in which patients who had been ambulatory suddenly experienced a change in condition and died within a day. As per this definition, 32 of 130 end-stage cancer patients (24.6%) who died at home during a period of 2 years experienced "sudden death". The reasons for sudden changes included liver rupture, liver failure, hematemesis/melena, and renal failure. It was presumed that 87.5% of patients who experienced "sudden death" had a life expectancy of days or weeks. Those who experienced sudden change in the presence of their family and died immediately thereafter or were found in a state of respiratory arrest accounted for 43.8% of cases. At the time of sudden change, sedation was performed in 34.3% of cases. Patient families were generally able to take action in a calm manner. Healthcare professionals and patient families should always be aware of the possibility of sudden changes in end-stage cancer patients. In addition, it is important for healthcare professionals to confirm how patients and their families perceive the disease condition, provide pain relief, and support families who are upset and anxious at the time of sudden changes. PMID:24712135

  2. Medication Errors in the Home: A Multisite Study of Children With Cancer

    PubMed Central

    Roblin, Douglas W.; Weingart, Saul N.; Houlahan, Kathleen E.; Degar, Barbara; Billett, Amy; Keuker, Christopher; Biggins, Colleen; Li, Justin; Wasilewski, Karen; Mazor, Kathleen M.

    2013-01-01

    OBJECTIVE: As home medication use increases, medications previously managed by nurses are now managed by patients and their families. Our objective was to describe the types of errors occurring in the home medication management of children with cancer. METHODS: In a prospective observational study at 3 pediatric oncology clinics in the northeastern and southeastern United States, patients undergoing chemotherapy and their parents were recruited from November 2007 through April 2011. We reviewed medical records and checked prescription doses. A trained nurse visited the home, reviewed medication bottles, and observed administration. Two physicians independently made judgments regarding whether an error occurred and its severity. Overall rates of errors were weighted to account for clustering within sites. RESULTS: We reviewed 963 medications and observed 242 medication administrations in the homes of 92 patients. We found 72 medication errors. Four errors led to significant patient injury. An additional 40 errors had potential for injury: 2 were life-threatening, 13 were serious, and 25 were significant. Error rates varied between study sites (40–121 errors per 100 patients); the weighted overall rate was 70.2 errors per 100 patients (95% confidence interval [CI]: 58.9–81.6). The weighted rate of errors with injury was 3.6 (95% CI: 1.7–5.5) per 100 patients and with potential to injure the patient was 36.3 (95% CI: 29.3–43.3) per 100 patients. Nonchemotherapy medications were more often involved in an error than chemotherapy. CONCLUSIONS: Medication errors were common in this multisite study of outpatient pediatric cancer care. Rates of preventable medication-related injuries in this outpatient population were comparable or higher than those found in studies of hospitalized patients. PMID:23629608

  3. A profile of homicides on the streets and in the homes of New York City.

    PubMed Central

    Tardiff, K; Marzuk, P M; Leon, A C; Hirsch, C S; Stajic, M; Portera, L; Hartwell, N

    1995-01-01

    Although prior research has found that homes containing firearms and illicit drug and ethanol users are more likely to be the scene of a homicide than homes that do not contain these elements, the authors studied homicides on the streets as well as in homes so as to assess the role of firearms, cocaine, and ethanol in both settings. Using the files of the Chief Medical Examiner, the authors reviewed all 4,468 homicides occurring in New York City in 1990 and 1991. The most frequent places of occurrence were the streets and other outdoor places (49.6 percent) and the victims' homes (19.3 percent). Firearms were the cause of death for 49.6 percent of homicides in the home and 80.3 percent of those on the streets. Use of cocaine and ethanol was found more frequently among victims killed on the streets than those killed at home. In addition, victims killed on the streets were more likely to be male, ages 15-24 years, and African American. Further research in regard to prevention and intervention strategies is needed, keeping in mind the different patterns of homicide on the streets compared with those occurring in other settings. PMID:7838937

  4. Molecular profiles of cancer stem-like cell populations in aggressive thyroid cancers.

    PubMed

    Dima, Mariavittoria; Pecce, Valeria; Biffoni, Mauro; Di Gioia, Cira Rosaria Tiziana; Tallini, Giovanni; Biffoni, Marco; Rosignolo, Francesca; Verrienti, Antonella; Sponziello, Marialuisa; Damante, Giuseppe; Russo, Diego; Durante, Cosimo

    2016-07-01

    A substantial proportion of patients with advanced thyroid carcinoma fail to respond to or at some point become refractory to conventional therapies. This resistance and the phenomena of thyroid cancer progression and metastasis themselves are thought to be related to tumor-cell sub-populations with stem-like properties. We isolated thyrospheres from four advanced thyroid carcinomas that were resistant to radioiodine therapy and analyzed their molecular profiles. ALDH activity and proteomic profile of main stem cell markers were used to assess stem cell properties. The TaqMan Low Density Array approach was used to evaluate the expression of several genes involved in the EMT process. The phosphorylation status of tyrosine kinase receptors (RTKs) was analyzed to identify potential markers for targeted therapies. We then investigated the effects of the EMT-inhibitor crizotinib on both cell proliferation and phosphorylation status of RTK targets. The cancer stem-like properties of a subset of cells from primary cultures of each tumor were demonstrated. A wide variability among thyrospheres arising from the four thyroid cancers in terms of ALDH activity, stem cell marker expression, and phosphoproteome profiling was present. Dysregulated expression of genes involved in the EMT was observed in all four thyrosphere lines. Treatment with crizotinib was ineffective in cancer stem-like cells, suggesting the presence of a mechanism of resistance in thyrospheres. Collectively, our data indicate that thyroid cancer stem-like populations vary markedly from tumor to tumor and require detailed molecular and biological characterization if they are to be used as the basis of "personalized" treatment of aggressive disease. PMID:26370117

  5. Quantitative proteomic profiling studies of pancreatic cancer stem cells.

    PubMed

    Dai, Lan; Li, Chen; Shedden, Kerby A; Lee, Cheong J; Li, Chenwei; Quoc, HuyVuong; Simeone, Diane M; Lubman, David M

    2010-07-01

    Analyzing subpopulations of tumor cells in tissue is a challenging subject in proteomic studies. Pancreatic cancer stem cells (CSCs) are such a group of cells that only constitute 0.2-0.8% of the total tumor cells but have been found to be the origin of pancreatic cancer carcinogenesis and metastasis. Global proteome profiling of pancreatic CSCs from xenograft tumors in mice is a promising way to unveil the molecular machinery underlying the signaling pathways. However, the extremely low availability of pancreatic tissue CSCs (around 10,000 cells per xenograft tumor or patient sample) has limited the utilization of currently standard proteomic approaches which do not work effectively with such a small amount of material. Herein, we describe the profiling of the proteome of pancreatic CSCs using a capillary scale shotgun technique by coupling offline capillary isoelectric focusing(cIEF) with nano reversed phase liquid chromatography(RPLC) followed by spectral counting peptide quantification. A whole cell lysate from 10,000 cells which corresponds to approximately 1 microg of protein material is equally divided for three repeated cIEF separations where around 300 ng of peptide material is used in each run. In comparison with a nontumorigenic tumor cell sample, among 1159 distinct proteins identified with FDR less than 0.2%, 169 differentially expressed proteins are identified after multiple testing corrections where 24% of the proteins are upregulated in the CSCs group. Ingenuity Pathway analysis of these differential expression signatures further suggests significant involvement of signaling pathways related to apoptosis, cell proliferation, inflammation, and metastasis. PMID:20486718

  6. 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. PMID:15979385

  7. Colon cancer prediction with genetic profiles using intelligent techniques

    PubMed Central

    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. PMID:19238250

  8. Integrative molecular profiling of routine clinical prostate cancer specimens

    PubMed Central

    Grasso, C. S.; Cani, A. K.; Hovelson, D. H.; Quist, M. J.; Douville, N. J.; Yadati, V.; Amin, A. M.; Nelson, P. S.; Betz, B. L.; Liu, C-J.; Knudsen, K. E.; Cooney, K. A.; Feng, F. Y.; McDaniel, A. S.; Tomlins, S. A.

    2015-01-01

    Background Comprehensive molecular profiling led to the recognition of multiple prostate cancer (PCa) molecular subtypes and driving alterations, but translating these findings to clinical practice is challenging. Patients and methods We developed a formalin-fixed paraffin-embedded (FFPE) tissue compatible integrative assay for PCa molecular subtyping and interrogation of relevant genetic/transcriptomic alterations (MiPC). We applied MiPC, which combines capture-based next generation sequencing and quantitative reverse transcription PCR (qRT-PCR), to 53 FFPE PCa specimens representing cases not well represented in frozen tissue cohorts, including 8 paired primary tumor and lymph node metastases. Results were validated using multiplexed PCR based NGS and Sanger sequencing. Results We identified known and novel potential driving, somatic mutations and copy number alterations, including a novel BRAF T599_V600insHT mutation and CYP11B2 amplification in a patient treated with ketoconazole (a potent CYP11B2 inhibitor). qRT-PCR integration enabled comprehensive molecular subtyping and provided complementary information, such as androgen receptor (AR) target gene module assessment in advanced cases and SPINK1 over-expression. MiPC identified highly concordant profiles for all 8 tumor/lymph node metastasis pairs, consistent with limited heterogeneity amongst driving events. MiPC and exome sequencing were performed on separately isolated conventional acinar PCa and prostatic small cell carcinoma (SCC) components from the same FFPE resection specimen to enable direct comparison of histologically distinct components. While both components showed TMPRSS2:ERG fusions, the SCC component exclusively harbored complete TP53 inactivation (frameshift variant and copy loss) and two CREBBP mutations. Conclusions Our results demonstrate the feasibility of integrative profiling of routine PCa specimens, which may have utility for understanding disease biology and enabling personalized

  9. 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.

  10. 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.

  11. 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

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

    PubMed

    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

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

    PubMed Central

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

    2011-01-01

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

  14. Implications of social isolation during cancer treatment. The implications of residence away from home during cancer treatment on patients' experiences: a comparative study.

    PubMed

    Payne, S; Jarrett, N; Jeffs, D; Brown, L

    2001-12-01

    With the centralisation and specialisation of cancer services, patients may have to travel considerable distances and stay away from their homes during treatment. This paper describes a comparative study that sought to identify the effects on patients of receiving chemotherapy and/or radiotherapy away from their homes, families and social support networks. Eighty four cancer patients treated in Southampton (42 from Guernsey and 42 from Southampton) agreed to participate in a structured interview and a standardised measure of social support. There were few differences in terms of satisfaction with services between Guernsey patients who stayed away from home during treatment and Southampton patients who lived at home. Counter-intuitively, Guernsey patients perceived themselves to have better social support. PMID:11682327

  15. 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…

  16. Parental Divorce, Death and Foster Home Placement as Related to Personality Profiles of Adolescents.

    ERIC Educational Resources Information Center

    Stolberg, Arnold L.; And Others.

    The purpose of the study was to investigate whether there was a consistent relationship between various deviant personality patterns and the status of the home from which the child came. Subjects were 300 adolescents from a population of 834 Caucasian teenagers, aged 12 to 18, not mentally deficient or retarded, from across the U.S., who were…

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

    PubMed

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

    2016-08-01

    Information regarding advanced cancer patients followed at home who are admitted to the hospital in the last days of life are lacking. The aim of this study was to assess the characteristics of patients who were hospitalized in the last days of life after being assisted by a home palliative care team. The secondary outcome was to identify possible risk factors for hospitalization. The charts were analyzed of a consecutive sample of advanced cancer patients admitted to hospital wards in the last days of life after being followed at home by a palliative care team. Of 550 consecutive patients followed at home, 138 (25.1 %) were admitted to the hospital. Younger patients were more likely to die in the hospital. In a logistic risk analysis adjusted for age, patients with lung and head-neck cancer were more likely to die in the hospital. Patients having a female relative or a female consort as a caregiver were more likely to die at home. CAGE-positive patients (7.25 %), and patients with a shorter period of home assistance were more likely transported to hospital before dying (p = 0.00 and p < 0.024, respectively). The most frequent reason for hospital admission was dyspnea. Admission was more frequent to the oncology ward. Patients who were admitted to the hospital died after a mean of 10.2 days (SD 8.2, range 0-40). This study provides preliminary data on the risk factors of hospitalization at the end of life for advanced cancer patients followed at home. PMID:26895033

  18. 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

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

    PubMed

    Wheeler, Scott R; Shi, Chanjuan; Holt, Jonathan A; Vnencak-Jones, Cindy L

    2016-06-01

    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

  20. DNA methylation profiling reveals a predominant immune component in breast cancers

    PubMed Central

    Dedeurwaerder, Sarah; Desmedt, Christine; Calonne, Emilie; Singhal, Sandeep K; Haibe-Kains, Benjamin; Defrance, Matthieu; Michiels, Stefan; Volkmar, Michael; Deplus, Rachel; Luciani, Judith; Lallemand, Françoise; Larsimont, Denis; Toussaint, Jérôme; Haussy, Sandy; Rothé, Françoise; Rouas, Ghizlane; Metzger, Otto; Majjaj, Samira; Saini, Kamal; Putmans, Pascale; Hames, Gérald; van Baren, Nicolas; Coulie, Pierre G; Piccart, Martine; Sotiriou, Christos; Fuks, François

    2011-01-01

    Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimizing treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but the involvement of the epigenome in breast cancer and its contribution to the complexity of the disease are still poorly understood. By means of DNA methylation profiling of 248 breast tissues, we have highlighted the existence of previously unrecognized breast cancer groups that go beyond the currently known ‘expression subtypes’. Interestingly, we showed that DNA methylation profiling can reflect the cell type composition of the tumour microenvironment, and in particular a T lymphocyte infiltration of the tumours. Further, we highlighted a set of immune genes having high prognostic value in specific tumour categories. The immune component uncovered here by DNA methylation profiles provides a new perspective for the importance of the microenvironment in breast cancer, holding implications for better management of breast cancer patients. PMID:21910250

  1. Gene expression profiles of small-cell lung cancers: molecular signatures of lung cancer.

    PubMed

    Taniwaki, Masaya; Daigo, Yataro; Ishikawa, Nobuhisa; Takano, Atsushi; Tsunoda, Tatsuhiko; Yasui, Wataru; Inai, Kouki; Kohno, Nobuoki; Nakamura, Yusuke

    2006-09-01

    To characterize the molecular mechanisms involved in the carcinogenesis and progression of small-cell lung cancer (SCLC) and identify molecules to be applied as novel diagnostic markers and/or for development of molecular-targeted drugs, we applied cDNA microarray profile analysis coupled with purification of cancer cells by laser-microbeam microdissection (LMM). Expression profiles of 32,256 genes in 15 SCLCs identified 252 genes that were commonly up-regulated and 851 transcripts that were down-regulated in SCLC cells compared with non-cancerous lung tissue cells. An unsupervised clustering algorithm applied to the expression data easily distinguished SCLC from the other major histological type of non-small cell lung cancer (NSCLC) and identified 475 genes that may represent distinct molecular features of each of the two histological types. In particular, SCLC was characterized by altered expression of genes related to neuroendocrine cell differentiation and/or growth such as ASCL1, NRCAM, and INSM1. We also identified 68 genes that were abundantly expressed both in advanced SCLCs and advanced adenocarcinomas (ADCs), both of which had been obtained from patients with extensive chemotherapy treatment. Some of them are known to be transcription factors and/or gene expression regulators such as TAF5L, TFCP2L4, PHF20, LMO4, TCF20, RFX2, and DKFZp547I048 as well as those encoding nucleotide-binding proteins such as C9orf76, EHD3, and GIMAP4. Our data provide valuable information for better understanding of lung carcinogenesis and chemoresistance. PMID:16865272

  2. Reduced Fatalism and Increased Prevention Behavior After Two High-Profile Lung Cancer Events

    PubMed Central

    PORTNOY, DAVID B.; LEACH, CORINNE R.; KAUFMAN, ANNETTE R.; MOSER, RICHARD P.; ALFANO, CATHERINE M.

    2015-01-01

    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. PMID:24274730

  3. Homing to solid cancers: a vascular checkpoint in adoptive cell therapy using CAR T-cells.

    PubMed

    Ager, Ann; Watson, H Angharad; Wehenkel, Sophie C; Mohammed, Rebar N

    2016-04-15

    The success of adoptive T-cell therapies for the treatment of cancer patients depends on transferred T-lymphocytes finding and infiltrating cancerous tissues. For intravenously transferred T-cells, this means leaving the bloodstream (extravasation) from tumour blood vessels. In inflamed tissues, a key event in extravasation is the capture, rolling and arrest of T-cells inside blood vessels which precedes transmigration across the vessel wall and entry into tissues. This depends on co-ordinated signalling of selectins, integrins and chemokine receptors on T-cells by their respective ligands which are up-regulated on inflamed blood vessels. Clinical data and experimental studies in mice suggest that tumour blood vessels are anergic to inflammatory stimuli and the recruitment of cytotoxic CD8(+)T-lymphocytes is not very efficient. Interestingly, and somewhat counter-intuitively, anti-angiogenic therapy can promote CD8(+)T-cell infiltration of tumours and increase the efficacy of adoptive CD8(+)T-cell therapy. Rather than inhibit tumour angiogenesis, anti-angiogenic therapy 'normalizes' (matures) tumour blood vessels by promoting pericyte recruitment, increasing tumour blood vessel perfusion and sensitizing tumour blood vessels to inflammatory stimuli. A number of different approaches are currently being explored to increase recruitment by manipulating the expression of homing-associated molecules on T-cells and tumour blood vessels. Future studies should address whether these approaches improve the efficacy of adoptive T-cell therapies for solid, vascularized cancers in patients. PMID:27068943

  4. 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.

  5. Place of death: hospital-based advanced home care versus conventional care. A prospective study in palliative cancer care.

    PubMed

    Ahlner-Elmqvist, Marianne; Jordhøy, Marit S; Jannert, Magnus; Fayers, Peter; Kaasa, Stein

    2004-10-01

    The purpose of this prospective nonrandomized study was to evaluate time spent at home, place of death and differences in sociodemographic and medical characteristics of patients, with cancer in palliative stage, receiving either hospital-based advanced home care (AHC), including 24-hour service by a multidisciplinary palliative care team or conventional hospital care (CC). Recruitment to the AHC group and to the study was a two-step procedure. The patients were assigned to either hospital-based AHC or CC according to their preferences. Following this, the patients were asked to participate in the study. Patients were eligible for the study if they had malignant disease, were older than 18 years and had a survival expectancy of 2-12 months. A total of 297 patients entered the study and 280 died during the study period of two and a half years, 117 in the AHC group and 163 in the CC group. Significantly more patients died at home in the AHC group (45%) compared with the CC group (10%). Preference for and referral to hospital-based AHC were not related to sociodemographic or medical characteristics. However, death at home was associated with living together with someone. Advanced hospital-based home care targeting seriously ill cancer patients with a wish to remain at home enable a substantial number of patients to die in the place they desire. PMID:15540666

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

    PubMed

    Narang, Pankaj; Dhapola, Parashar; Chowdhury, Shantanu

    2016-01-01

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

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

    PubMed 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

  8. Metabolic Profiles are Principally Different between Cancers of the Liver, Pancreas and Breast

    PubMed Central

    Budhu, Anuradha; Terunuma, Atsushi; Zhang, Geng; Hussain, S. Perwez; Ambs, Stefan; Wang, Xin Wei

    2014-01-01

    Molecular profiling of primary tumors may facilitate the classification of patients with cancer into more homogenous biological groups to aid clinical management. Metabolomic profiling has been shown to be a powerful tool in characterizing the biological mechanisms underlying a disease but has not been evaluated for its ability to classify cancers by their tissue of origin. Thus, we assessed metabolomic profiling as a novel tool for multiclass cancer characterization. Global metabolic profiling was employed to identify metabolites in paired tumor and non-tumor liver (n=60), breast (n=130) and pancreatic (n=76) tissue specimens. Unsupervised principal component analysis showed that metabolites are principally unique to each tissue and cancer type. Such a difference can also be observed even among early stage cancers, suggesting a significant and unique alteration of global metabolic pathways associated with each cancer type. Our global high-throughput metabolomic profiling study shows that specific biochemical alterations distinguish liver, pancreatic and breast cancer and could be applied as cancer classification tools to differentiate tumors based on tissue of origin. PMID:25210494

  9. 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

  10. 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

  11. Profile of the DNA recognition site of the archaeal homing endonuclease I-DmoI.

    PubMed Central

    Aagaard, C; Awayez, M J; Garrett, R A

    1997-01-01

    I- Dmo I is a homing enzyme of the LAGLI-DADG type that recognizes up to 20 bp of DNA and is encoded by an archaeal intron of the hyperthermophilic archaeon Desulfurococcus mobilis . A combined mutational and DNA footprinting approach was employed to investigate the specificity of the I- Dmo I-substrate interaction. The results indicate that the enzyme binds primarily to short base paired regions that border the sites of DNA cleavage and intron insertion. The minimal substrate spans no more than 15 bp and while sequence degeneracy is tolerated in the DNA binding regions, the sequence and size of the cleavage region is highly conserved. The enzyme has a slow turnover rate and cuts the coding strand with a slight preference over the non-coding strand. Complex formation produces some distortion of the DNA double helix within the cleavage region. The data are compatible with the two DNA-binding domains of I- Dmo I bridging the minor groove, where cleavage occurs, and interacting within the major groove on either side, thereby stabilizing a distorted DNA double helix. This may provide a general mode of DNA interaction at least for the LAGLIDADG-type homing enzymes. PMID:9092657

  12. 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…

  13. Patients with cancer and family caregivers: management of symptoms caused by cancer or cancer therapy at home

    PubMed Central

    Hazelwood, Daniela Maria; Wallner, Martin; Anderson, Kathryn Hoehn; Mayer, Hanna

    2013-01-01

    Summary People are diagnosed with cancer sooner nowadays thanks to increased awareness and improvements in cancer screenings. Patients are able to live longer due to cancer treatment regimens; however, they suffer the consequences of living with cancer and therapy-related symptoms. Symptom management is challenging for both patients and family caregivers. Therefore, family members must be integrated in the patient’s care plan. For this review, a literature search was conducted to determine what types of interventions were available that involved family members of cancer patients with the management of cancer and therapy-related symptoms. The following interventions were found that were designed for the family caregivers or both the patient and caregiver to aide with symptom management: pain intervention program, massage therapy, telephone intervention, self-efficacy improvement, coping enhancement and a multidimensional intervention. A positive effect was noted in all the studies, but several had no significance in the patient intervention group but did in the caregiver intervention group. However, studies indicated decreased symptom intensity for various symptoms, decreased symptom distress for both the patient and caregiver, increased self-efficacy of the family member, and increased satisfaction with certain interventions. Further research should be conducted on both existing interventions to better determine their effect and on family symptom management of cancer patients as they need support from healthcare professionals as well. PMID:24027658

  14. Colorectal Cancer Screening Rates Increased after Exposure to the Patient-Centered Medical Home (PCMH)

    PubMed Central

    Green, Beverly B.; Anderson, Melissa L.; Chubak, Jessica; Baldwin, Laura Mae; Tuzzio, Leah; Catz, Sheryl; Cole, Alison; Vernon, Sally W.

    2016-01-01

    Objective The patient-centered medical home (PCMH) includes comprehensive chronic illness and preventive services, including identifying patients who are overdue for colorectal cancer screening (CRCS). The association between PCMH implementation and CRCS during the Systems of Support to Increase Colorectal Cancer Screening Trial (SOS) is described. Methods The SOS enrolled 4664 patients from 21 clinics from August 2008 to November 2009. Patients were randomized to usual care, mailed fecal kits, kits plus brief assistance, or kits plus assistance and navigation. A PCMH model that included a workflow for facilitating CRCS was implemented at all study clinics in late 2009. Patients enrolled early had little exposure to the PCMH, whereas patients enrolled later were exposed during most of their first year in the trial. Logistic regression models were used to assess the association between PCMH exposure and CRCS. Results Usual care patients with ≥8 months in the PCMH had higher CRCS rates than those with ≤4 months in the PCMH (adjusted difference, 10.1%; 95% confidence interval, 5.7–14.6). SOS interventions led to significant increases in CRCS, but the magnitude of effect was attenuated by exposure to the PCMH (P for interaction = .01). Conclusion Exposure to a PCMH was associated with higher CRCS rates. Automated mailed and centrally delivered stepped interventions increased CRCS rates, even in the presence of a PCMH. (J Am Board Fam Med 2016;29:191–200.) PMID:26957375

  15. A Data Similarity-Based Strategy for Meta-analysis of Transcriptional Profiles in Cancer

    PubMed Central

    Xiang, Yuzhu; Shyr, Yu; Chen, Xi; Lehmann, Brian David; Viox, Daniel Joseph; George, Alfred L.; Yi, Yajun

    2013-01-01

    Background Robust transcriptional signatures in cancer can be identified by data similarity-driven meta-analysis of gene expression profiles. An unbiased data integration and interrogation strategy has not previously been available. Methods and Findings We implemented and performed a large meta-analysis of breast cancer gene expression profiles from 223 datasets containing 10,581 human breast cancer samples using a novel data similarity-based approach (iterative EXALT). Cancer gene expression signatures extracted from individual datasets were clustered by data similarity and consolidated into a meta-signature with a recurrent and concordant gene expression pattern. A retrospective survival analysis was performed to evaluate the predictive power of a novel meta-signature deduced from transcriptional profiling studies of human breast cancer. Validation cohorts consisting of 6,011 breast cancer patients from 21 different breast cancer datasets and 1,110 patients with other malignancies (lung and prostate cancer) were used to test the robustness of our findings. During the iterative EXALT analysis, 633 signatures were grouped by their data similarity and formed 121 signature clusters. From the 121 signature clusters, we identified a unique meta-signature (BRmet50) based on a cluster of 11 signatures sharing a phenotype related to highly aggressive breast cancer. In patients with breast cancer, there was a significant association between BRmet50 and disease outcome, and the prognostic power of BRmet50 was independent of common clinical and pathologic covariates. Furthermore, the prognostic value of BRmet50 was not specific to breast cancer, as it also predicted survival in prostate and lung cancers. Conclusions We have established and implemented a novel data similarity-driven meta-analysis strategy. Using this approach, we identified a transcriptional meta-signature (BRmet50) in breast cancer, and the prognostic performance of BRmet50 was robust and applicable across a

  16. Molecular profile of liquid biopsies: next generation biomarkers to improve lung cancer treatment

    PubMed Central

    Bianchi, Fabrizio

    2015-01-01

    Molecular profiling of liquid biopsies is now emerging as pivotal for cancer biomarker discovery. The low-invasive nature of the approach used for collecting biospecimens (i.e. blood, urine, saliva, etc.) may allow a widespread application of novel molecular diagnostics based on liquid biopsies. This is relevant, for example, in cancer screening programmes where it is essential to reduce costs and the complexity of screening tests in order to increase study compliance and effectiveness. Here, I discuss recent advances in biomarkers for the early cancer detection and prediction of chemotherapy response based on the molecular profiling of liquid biopsies. PMID:26635902

  17. 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…

  18. Activity-based protein profiling for biochemical pathway discovery in cancer

    PubMed Central

    Nomura, Daniel K.; Dix, Melissa M.; Cravatt, Benjamin F.

    2011-01-01

    Large-scale profiling methods have uncovered numerous gene and protein expression changes that correlate with tumorigenesis. However, determining the relevance of these expression changes and which biochemical pathways they affect has been hindered by our incomplete understanding of the proteome and its myriad functions and modes of regulation. Activity-based profiling platforms enable both the discovery of cancer-relevant enzymes and selective pharmacological probes to perturb and characterize these proteins in tumour cells. When integrated with other large-scale profiling methods, activity-based proteomics can provide insight into the metabolic and signalling pathways that support cancer pathogenesis and illuminate new strategies for disease diagnosis and treatment. PMID:20703252

  19. A self-directed home yoga programme for women with breast cancer during chemotherapy: A feasibility study.

    PubMed

    Komatsu, Hiroko; Yagasaki, Kaori; Yamauchi, Hideko; Yamauchi, Teruo; Takebayashi, Toru

    2016-06-01

    Recent studies suggest yoga as a promising approach for improving the cognitive function of cancer survivors. We studied whether a self-directed home yoga programme was feasible for patients with breast cancer who were undergoing chemotherapy. Participants' preferences for the type of yoga course and the clinical effects of the programme were also assessed. In this study, 18 women (mean age, 43.9 years) were enrolled (44.7% recruitment rate). Of the participants, 63.6% had stage II cancer and 71.4% received adjuvant chemotherapy. Favourable retention (86%), adherence (94.4%) and acceptability (96.5%) rates were determined. Most (94.4%) of the women practiced the home programme more than twice a week on average. The participants preferred to gradually increase the intensity of the exercises. We only observed improvements in the cognitive aspects of fatigue. No serious adverse events were encountered during the programme. This self-directed home yoga programme was safe and feasible for patients with breast cancer undergoing chemotherapy. PMID:26643264

  20. The Impact of Genomic Profiling for Novel Cancer Therapy--Recent Progress in Non-Small Cell Lung Cancer.

    PubMed

    Xie, Jingwu; Zhang, Xiaoli

    2016-01-20

    There is high expectation for significant improvements in cancer patient care after completion of the human genome project in 2003. Through pains-taking analyses of genomic profiles in cancer patients, a number of targetable gene alterations have been discovered, with some leading to novel therapies, such as activating mutations of EGFR, BRAF and ALK gene fusions. As a result, clinical management of cancer through targeted therapy has finally become a reality for a subset of cancers, such as lung adenocarcinomas and melanomas. In this review, we summarize how gene mutation discovery leads to new treatment strategies using non-small cell lung cancer (NSCLC) as an example. We also discuss possible future implications of cancer genome analyses. PMID:26842989

  1. Personalized chemotherapy profiling using cancer cell lines from selectable mice

    PubMed Central

    Kamiyama, Hirohiko; Rauenzahn, Sherri; Shim, Joong Sup; Karikari, Collins A.; Feldmann, Georg; Hua, Li; Kamiyama, Mihoko; Schuler, F. William; Lin, Ming-Tseh; Beaty, Robert M.; Karanam, Balasubramanyam; Liang, Hong; Mullendore, Michael E.; Mo, Guanglan; Hidalgo, Manuel; Jaffee, Elizabeth; Hruban, Ralph H.; Jinnah, H. A.; Roden, Richard B. S.; Jimeno, Antonio; Liu, Jun O.; Maitra, Anirban; Eshleman, James R.

    2013-01-01

    Purpose High-throughput chemosensitivity testing of low-passage cancer cell lines can be used to prioritize agents for personalized chemotherapy. However, generating cell lines from primary cancers is difficult, because contaminating stromal cells overgrow the malignant cells. Experimental Design We produced a series of hypoxanthine phosphoribosyl transferase (hprt)-null immunodeficient mice. During growth of human cancers in these mice, hprt-null murine stromal cells replace their human counterparts. Results Pancreatic and ovarian cancers explanted from these mice were grown in selection media to produce pure human cancer cell lines. We screened one cell line with a 3,131-drug panel and identified seventy-seven FDA approved drugs with activity, including two novel drugs to which the cell line was uniquely sensitive. Xenografts of this carcinoma were selectively responsive to both drugs. Conclusion Chemotherapy can be personalized using patient-specific cell lines derived in biochemically selectable mice. PMID:23340293

  2. Metabolic Profiling Reveals PAFAH1B3 as a Critical Driver of Breast Cancer Pathogenicity

    PubMed Central

    Mulvihill, Melinda M.; Benjamin, Daniel I.; Ji, Xiaodan; Le Scolan, Erwan; Louie, Sharon M.; Shieh, Alice; Green, McKenna; Narasimhalu, Tara; Morris, Patrick J.; Luo, Kunxin; Nomura, Daniel K.

    2014-01-01

    Many studies have identified metabolic pathways that underlie cellular transformation, but the metabolic drivers of cancer progression remain less well understood. The Hippo transducer pathway has been shown to confer malignant traits on breast cancer cells. In this study, we used metabolic mapping platforms to identify biochemical drivers of cellular transformation and malignant progression driven through RAS and the Hippo pathway in breast cancer, and identified platelet activating factor acetylhydrolase 1B3 (PAFAH1B3) as a key metabolic driver of breast cancer pathogenicity that is upregulated in primary human breast tumors and correlated with poor prognosis. Metabolomic profiling suggests that PAFAH1B3 inactivation attenuates cancer pathogenicity through enhancing tumor-suppressing signaling lipids. Our studies provide a map of altered metabolism that underlies breast cancer progression and put forth PAFAH1B3 as a critical metabolic node in breast cancer. PMID:24954006

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

    PubMed Central

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

    2012-01-01

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

  4. Lung cancer signatures in plasma based on proteome profiling of mouse tumor models.

    PubMed

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

    2011-09-13

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

  5. Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal

    PubMed Central

    Gao, Jianjiong; Aksoy, Bülent Arman; Dogrusoz, Ugur; Dresdner, Gideon; Gross, Benjamin; Sumer, S. Onur; Sun, Yichao; Jacobsen, Anders; Sinha, Rileen; Larsson, Erik; Cerami, Ethan; Sander, Chris; Schultz, Nikolaus

    2014-01-01

    The cBioPortal for Cancer Genomics (http://cbioportal.org) provides a Web resource for exploring, visualizing, and analyzing multidimensional cancer genomics data. The portal reduces molecular profiling data from cancer tissues and cell lines into readily understandable genetic, epigenetic, gene expression, and proteomic events. The query interface combined with customized data storage enables researchers to interactively explore genetic alterations across samples, genes, and pathways and, when available in the underlying data, to link these to clinical outcomes. The portal provides graphical summaries of gene-level data from multiple platforms, network visualization and analysis, survival analysis, patient-centric queries, and software programmatic access. The intuitive Web interface of the portal makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries. Here, we provide a practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics. PMID:23550210

  6. 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

  7. Radon in The Home May Be Linked to Blood Cancers in Women

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_158632.html Radon in the Home May Be Linked to Blood ... strong link between exposure to high levels of radon in the home and women's risk of blood ...

  8. Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

    PubMed Central

    2010-01-01

    Background Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs

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

    PubMed

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

    2016-01-01

    Cancer cells have broken circadian clocks when compared to their normal tissue counterparts. Moreover, it has been shown in breast cancer that disruption of common circadian oscillations is associated with a more negative prognosis. Numerous studies, focused on canonical circadian genes in breast cancer cell lines, have suggested that there are no mRNA circadian-like oscillations. Nevertheless, cancer cell lines have not been extensively characterized and it is unknown to what extent the circadian oscillations are disrupted. We have chosen representative non-cancerous and cancerous breast cell lines (MCF-10A, MCF-7, ZR-75-30, MDA-MB-231 and HCC-1954) in order to determine the degree to which the circadian clock is damaged. We used serum shock to synchronize the circadian clocks in culture. Our aim was to initially observe the time course of gene expression using cDNA microarrays in the non-cancerous MCF-10A and the cancerous MCF-7 cells for screening and then to characterize specific genes in other cell lines. We used a cosine function to select highly correlated profiles. Some of the identified genes were validated by quantitative polymerase chain reaction (qPCR) and further evaluated in the other breast cancer cell lines. Interestingly, we observed that breast cancer and non-cancerous cultured cells are able to generate specific circadian expression profiles in response to the serum shock. The rhythmic genes, suggested via microarray and measured in each particular subtype, suggest that each breast cancer cell type responds differently to the circadian synchronization. Future results could identify circadian-like genes that are altered in breast cancer and non-cancerous cells, which can be used to propose novel treatments. Breast cell lines are potential models for in vitro studies of circadian clocks and clock-controlled pathways. PMID:27010605

  10. Amino acid profiling as a method of discovering biomarkers for early diagnosis of cancer.

    PubMed

    Simińska, Edyta; Koba, Marcin

    2016-06-01

    Cancer is one of the main causes of mortality in the world and its early detection significantly increases chances of patients' survival. High cancer mortality rate is caused mainly by late-stage diagnosis and lack of non-invasive and reliable methods for early diagnosis, such as plasma biomarkers. The incidence of cancers in the world still grows so it is crucial to develop a new, faster, high specificity and more sensitive diagnostic technologies. Several recent researchers indicate amino acids as a potential marker for cancer detection. An ideal cancer biomarker should be characterized by high specificity and sensitivity, reliability, ease of measurement and, what is important, ability to detect disease in its early stage. This study is focused on indicating metabolic amino acid profiling as a method of identifying biomarkers for cancer early detection and screening. Presented results are derived from the most recent studies where patients in early, often asymptomatic stages of disease constituted a large percentage of all the patients and, what is important, where researchers have observed alterations in these patients' amino acid profiles. This review is concentrated on analyzing studies on the most common cancers with high mortality rate. Inventing effective methods of early diagnosis is particularly important in case of such diseases. Research presented in this publication is focused on patients with lung, breast and colon cancer. In all analyzed cases, significant changes in the amino acid profile in cancer patients comparing to healthy controls were observed. This study indicates potential of amino acid profiling as method for early cancer detection. PMID:27033065

  11. Mass Spectrometry–based Proteomic Profiling of Lung Cancer

    PubMed Central

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

    2009-01-01

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

  12. Profile of palbociclib in the treatment of metastatic breast cancer

    PubMed Central

    Ehab, Moataz; Elbaz, Mohamad

    2016-01-01

    Breast cancer is the most common cancer diagnosed in women. Each year, thousands die either because of disease progression or failure of treatment. Breast cancer is classified into different subtypes based on the molecular expression of estrogen receptor (ER), progesterone receptor, and/or human epidermal growth factor receptor 2 (HER2). These receptors represent important therapeutic targets either through monoclonal antibodies or through small-molecule inhibitors directed toward them. However, up to 40% of patients develop either a primary or a secondary resistance to the current treatments. Therefore, there is an urgent need for investigating new targets in order to overcome the resistance and/or enhance the current therapies. Cell cycle is altered in many human cancers, especially in breast cancer. Cyclin-dependent kinases (CDKs), especially CDK4 and CDK6, play a pivotal role in cell cycle progression that makes them potential targets for new promising therapies. CDK inhibition has shown strong antitumor activities, ranging from cytostatic antiproliferative effects to synergistic effects in combination with other antitumor drugs. In order to overcome the drawbacks of the first-generation CDK inhibitors, recently, new CDK inhibitors have emerged that are more selective to CDK4 and CDK6 such as palbociclib, which is the most advanced CDK4/6 inhibitor in trials. In preclinical studies, palbociclib has shown a very promising antitumor activity, especially against ERα+ breast cancer subtype. Palbociclib has gained world attention, and US the Food and Drug Administration has accelerated its approval for first-line treatment in combination with letrozole for the first-line systematic treatment of postmenopausal women with ERα+/HER2− locally advanced or metastatic breast cancer. In this review, we discuss the potential role of CDK inhibition in breast cancer treatment, and focus on palbociclib progress from preclinical studies to clinical trials with mentioning the

  13. [Organisational diagnosis of a home care-coordinating unit in oncology: which choices for the comprehensive cancer center of Lyon?].

    PubMed

    Chvetzoff, Gisèle; Chvetzoff, Roland; Devaux, Yves; Teil, A; Chalencon, J; Lancry, L; Kante, V; Poncelas, C; Sontag, P; Tretiakoff, C; Philip, T

    2006-10-01

    Lyon comprehensive cancer center developed a home care-coordinating unit (HCCU) allowing a wide range of cancer care at home. We present the results of an organisational and strategical analysis of the unit, in relation with internal and external contexts. We describe the functioning of the unit, modelled from the daily follow-up of professionnels. Patient discharge is initiated by the oncologist at the inpatient clinic, at the day-hospital or at outpatient visit. After consent of the patient and relatives, the HCCU (nurses and medical oncologists) evaluates patient's needs, organises hospital discharge (contacts with community nurses and general practitioner, supply of medical appliances and drugs), and provides follow-up and counselling to patient and caregivers. The HCCU works in a challenging environment, with both partners and competitors. Within the hospital, it collaborates with all other units. Outside the hospital, partners are, besides patients themselves; general practitioners and community nurses home care agencies and network services, private medical appliance providers, and public health authorities. The unit might evolve towards formal home hospitalisation or community-hospital network. Collaboration of both structure closely associated with hospital could allow to provide continuous and graduated care by the same caregivers even if administrative structures change. PMID:17074663

  14. 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

  15. How Can Gastric Cancer Molecular Profiling Guide Future Therapies?

    PubMed

    Corso, Simona; Giordano, Silvia

    2016-07-01

    Gastric cancer is the third greatest global cause of cancer-related deaths. Despite its high prevalence, only recently have comprehensive genomic surveys shed light on its molecular alterations. As surgery is the only curative treatment strategy and chemotherapy has shown limited efficacy, new treatments are urgently needed. Many molecular therapies for gastric cancer have entered clinical trials but-apart from Trastuzumab and Ramucirumab-all have failed. We analyze the current knowledge of the genetic 'landscape' of gastric cancers, elaborating on novel, preclinical approaches. We posit that this knowledge lays the basis for identifying bona fide molecular targets and developing solid therapeutic approaches, requiring accurate patient selection and taking advantage of preclinical models to assist clinical development of novel combination strategies. PMID:27260398

  16. 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.

  17. 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

  18. Mutation Profile of Well-Differentiated Thyroid Cancer in Asians

    PubMed Central

    Song, Young Shin; Lim, Jung Ah

    2015-01-01

    Recent advances in molecular diagnostics have led to significant insights into the genetic basis of thyroid tumorigenesis. Among the mutations commonly seen in thyroid cancers, the vast majority are associated with the mitogen-activated protein kinase pathway. B-Raf proto-oncogene (BRAF) mutations are the most common mutations observed in papillary thyroid cancers (PTCs), followed by RET/PTC rearrangements and RAS mutations, while follicular thyroid cancers are more likely to harbor RAS mutations or PAX8/peroxisome proliferator-activated receptor γ (PPARγ) rearrangements. Beyond these more common mutations, alterations in the telomerase reverse transcriptase (TERT) promoter have recently been associated with clinicopathologic features, disease prognosis, and tumorigenesis in thyroid cancer. While the mutations underlying thyroid tumorigenesis are well known, the frequency of these mutations is strongly associated with geography, with clear differences reported between Asian and Western countries. Of particular interest is the prevalence of BRAF mutations, with Korean patients exhibiting the highest rate of BRAF-associated thyroid cancers in the world. Here, we review the prevalence of each of the most common mutations in Asian and Western countries, and identify the characteristics of well-differentiated thyroid cancer in Asians. PMID:26435130

  19. Possible detection of pancreatic cancer by plasma protein profiling.

    PubMed

    Honda, Kazufumi; Hayashida, Yasuharu; Umaki, Tomoko; Okusaka, Takuji; Kosuge, Tomoo; Kikuchi, Satoru; Endo, Mitsufumi; Tsuchida, Akihiko; Aoki, Tatsuya; Itoi, Takao; Moriyasu, Fuminori; Hirohashi, Setsuo; Yamada, Tesshi

    2005-11-15

    The survival rate of pancreatic cancer patients is the lowest among those with common solid tumors, and early detection is one of the most feasible means of improving outcomes. We compared plasma proteomes between pancreatic cancer patients and sex- and age-matched healthy controls using surface-enhanced laser desorption/ionization coupled with hybrid quadrupole time-of-flight mass spectrometry. Proteomic spectra were generated from a total of 245 plasma samples obtained from two institutes. A discriminating proteomic pattern was extracted from a training cohort (71 pancreatic cancer patients and 71 healthy controls) using a support vector machine learning algorithm and was applied to two validation cohorts. We recognized a set of four mass peaks at 8,766, 17,272, 28,080, and 14,779 m/z, whose mean intensities differed significantly (Mann-Whitney U test, P < 0.01), as most accurately discriminating cancer patients from healthy controls in the training cohort [sensitivity of 97.2% (69 of 71), specificity of 94.4% (67 of 71), and area under the curve value of 0.978]. This set discriminated cancer patients in the first validation cohort with a sensitivity of 90.9% (30 of 33) and a specificity of 91.1% (41 of 45), and its discriminating capacity was further validated in an independent cohort at a second institution. When combined with CA19-9, 100% (29 of 29 patients) of pancreatic cancers, including early-stage (stages I and II) tumors, were detected. Although a multi-institutional large-scale study will be necessary to confirm clinical significance, the biomarker set identified in this study may be applicable to using plasma samples to diagnose pancreatic cancer. PMID:16288055

  20. Educating Hispanic Women About Breast Cancer Prevention: Evaluation of a Home-Based Promotora-Led Intervention

    PubMed Central

    Coronado, Gloria D.; Espinoza, Noah; Islas, Ilda; Ibarra, Genoveva; Thompson, Beti

    2010-01-01

    Abstract Objectives Trained community health promoters (i.e., promotoras) conducted home-based group educational interventions (home health parties) to educate Hispanic women from the Lower Yakima Valley of Washington state about breast cancer and mammography screening. Methods Women aged 40–79 participating in the parties completed baseline and follow-up surveys 6 months postintervention (n = 70). Changes in general cancer knowledge, breast cancer screening practices, and intentions to be screened among participants from baseline to follow-up were measured using McNemar's test for marginal homogeneity to evaluate the effectiveness of the parties. Results The average age of the sample was 50.0 years (standard deviation [SD] 10.0), 84% reported less than an eighth grade education, and 54% were covered by the state's Basic Health Care Plan. Significant changes between baseline and follow-up were observed with respect to (1) believing that risk of cancer could not be reduced (41% vs. 15%, respectively, p = 0.001), (2) ever having a mammogram (83% vs. 91%, p = 0.014), (3) discussing a mammogram with a doctor (37% vs. 67%, p < 0.001), and (4) intending to have a mammogram within the next few months among women who did not report having a mammogram between baseline and follow-up (61% vs. 81%, p = 0.046). Conclusions Participation in home-based group educational interventions delivered by promotoras may be associated with improved breast cancer screening practices among Hispanic women. PMID:20849288

  1. 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

  2. The Valuable Role of Measuring Serum Lipid Profile in Cancer Progression

    PubMed Central

    Ghahremanfard, Farahnaz; Mirmohammadkhani, Majid; Shahnazari, Banafsheh; Gholami, Golnaz; Mehdizadeh, Jamileh

    2015-01-01

    Objective Serum lipid levels are not only associated with etiology, but also with prognosis in cancer. To investigate this issue further, we aimed to evaluate the serum levels of lipids in association with the most important prognostic indicators in cancer patients at the start of chemotherapy. Methods In a retrospective cross-sectional study, using existing medical records obtained from 2009–2014, the data of all incident cancer cases in Iranian patients referred to the Semnan oncology clinic for chemotherapy were analyzed. Data on demographics, cancer type, prognostic indicators (e.g. lymph node involvement, metastasis, and stage of disease), as well as the patient’s lipid profile were collected. We used multiple logistic regression models to show the relationship between prognosis indicators and lipid profile adjusting for age, gender, and type of cancer. Results The data of 205 patients was gathered. We found a significant difference in the lipid profile between different types of cancers (breast, colon, gastric, and ovarian). With the exception of high-density lipoprotein levels in women, which were higher than in men, the means of other lipid profiles were similar between the genders. There was a significant association between higher levels of low-density lipoprotein (LDL >110mg/dL) in the serum and metastasis (adjusted odds ratio=2.4, 95% CI 1.2–3.5). No significant association was reported between lipid profile and lymph nodes involvement and stage of the disease. Conclusion Our study suggested a benefit of measuring serum levels of lipids for predicting cancer progression. Increased LDL levels can be considered a predictive factor for increasing the risk of metastasis. PMID:26421116

  3. Protein profile study of the cervical cancer using HPLC-LIF

    NASA Astrophysics Data System (ADS)

    Sujatha; Rai, Lavanya; Krishnanand, B. R.; Mahato, K. K.; Kartha, V. B.; C, Santhosh

    2006-02-01

    Optical methods and proteomics investigations are becoming promising approaches for early detection of many diseases, which remain clinically silent for long periods. We have used efficient High Performance Liquid Chromatography (HPLC) separation combined with highly sensitive laser induced fluorescence detection of proteins present in clinical samples for diagnostic applications in cervical cancer. The protein profile and the fluorescence of individual proteins were simultaneously recorded using our HPLC-LIF system. Protein profiles (Chromatogram) of serum from normal male and female volunteers with and without tobacco habits, and malignant serum samples were studied. Protein profiles were also recorded for lysates of exfoliated cells collected from Pap smear of normal and cancer patients. The protein profile patterns were subjected to Principal component Analysis. Discrimination of normal and malignant samples were achieved with very high sensitivity and specificity.

  4. Radon in The Home May Be Linked to Blood Cancers in Women

    MedlinePlus

    ... cancer and is the second leading cause of lung cancer in the United States, the researchers said. The American Cancer Society collected ... lifetime risk of hematological [blood] cancers in the United States is about 2 ... already associated with lung cancer, and if other studies confirm the link ...

  5. Gene cataloging and expression profiling in human gastric cancer cells by expressed sequence tags.

    PubMed

    Kim, Nam-Soon; Hahn, Yoonsoo; Oh, Jung-Hwa; Lee, Ju-Yeon; Oh, Kyung-Jin; Kim, Jeong-Min; Park, Hong-Seog; Kim, Sangsoo; Song, Kyu-Sang; Rho, Seung-Moo; Yoo, Hyang-Sook; Kim, Yong Sung

    2004-06-01

    To understand the molecular mechanism associated with gastric carcinogenesis, we identified genes expressed in gastric cancer cell lines and tissues. Of 97,609 high-quality ESTs sequenced from 36 cDNA libraries, 92,545 were coalesced into 10,418 human Unigene clusters (Build 151). The gene expression profile was produced by counting the cluster frequencies in each library. Although the profiles of highly expressed genes varied greatly from library to library, those genes related to cell structure formation, heat shock proteins, the glycolysis pathway, and the signaling pathway were highly represented in human gastric cancer cell lines and in primary tumors. Conversely, the genes encoding immunoglobulins, ribosomal proteins, and digestive proteins were down-regulated in gastric cancer cell lines and tissues compared to normal tissues. The transcription levels of some of these genes were confirmed by RT-PCR. We found that genes related to cell adhesion, apoptosis, and cytoskeleton formation were particularly up-regulated in the gastric cancer cell lines established from malignant ascites compared to those from primary tumors. This comprehensive molecular profiling of human gastric cancer should be useful for elucidating the genetic events associated with human gastric cancer. PMID:15177556

  6. Comprehensive molecular profiling of the B7 family of immune-regulatory ligands in breast cancer.

    PubMed

    Xu, Zhenyu; Shen, Jing; Wang, Maggie Haitian; Yi, Tao; Yu, Yangyang; Zhu, Yinxin; Chen, Bo; Chen, Jianping; Li, Longfei; Li, Minxing; Zuo, Jian; Jiang, Hui; Zhou, Dexi; Luan, Jiajie; Xiao, Zhangang

    2016-08-01

    The B7 gene family has crucial roles in the regulation of adaptive cellular immunity. In cancer, deregulation of co-inhibitory B7 molecules is associated with reduced antitumor immunity and cancer immune evasion. FDA approval of cancer immunotherapy antibodies against cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1)-both ligands of the B7 family-demonstrate the impact of these checkpoint regulators in cancer. Using data from cBioPortal, we performed comprehensive molecular profiling of the 10 currently known B7 family proteins in 105 different cancers. B7 family members were amplified in breast cancer: with B7 mRNA levels upregulated in a cohort of 1,098 patients with all types of breast cancer and in 82 patients with triple-negative breast cancer. Promoter methylation analysis indicated an epigenetic basis for deregulation of certain B7 family genes in breast cancer. Moreover, patients with B7-H6 genomic alterations had significantly worse overall survival, and certain clinical attributes were associated with B7-H6 expression, which indicates that B7-H6 may be a potential target for breast cancer immunotherapy. Finally, using network analysis (based on data from cBioportal), we identified BTLA, MARCH8, PLSCR1 and SMAD3 as potentially involved in T cell signaling under regulation of B7 family proteins. PMID:27622076

  7. The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

    PubMed Central

    Kon, Oi Lian; Yip, Tai-Tung; Ho, Meng Fatt; Chan, Weng Hoong; Wong, Wai Keong; Tan, Soo Yong; Ng, Wai Har; Kam, Siok Yuen; Eng, Alvin KH; Ho, Patrick; Viner, Rosa; Ong, Hock Soo; Kumarasinghe, M Priyanthi

    2008-01-01

    Background Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints. Methods Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides) was used for validation. Results By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p < 0.01). Multimarker clustering showed two distinctive proteomic profiles independent of age and ethnicity. Eighteen of 19 cancer samples clustered together (sensitivity 95%) while 27/36 of non-cancer samples clustered in a second group. Nine non-cancer samples that clustered with cancer samples included 5 pre-malignant lesions (1 adenomatous polyp and 4 intestinal metaplasia). Validation using a second sample set showed the sensitivity and specificity to be 88% and 93%, respectively. Positive predictive value of the combined data was 0.80. Selected peptide sequencing identified pepsinogen C and pepsin A activation peptide as significantly down-regulated and alpha-defensin as significantly up-regulated. Conclusion This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions. PMID:18950519

  8. Comprehensive analysis of the transcriptional profile of the Mediator complex across human cancer types.

    PubMed

    Syring, Isabella; Klümper, Niklas; Offermann, Anne; Braun, Martin; Deng, Mario; Boehm, Diana; Queisser, Angela; von Mässenhausen, Anne; Brägelmann, Johannes; Vogel, Wenzel; Schmidt, Doris; Majores, Michael; Schindler, Anne; Kristiansen, Glen; Müller, Stefan C; Ellinger, Jörg; Shaikhibrahim, Zaki; Perner, Sven

    2016-04-26

    The Mediator complex is a key regulator of gene transcription and several studies demonstrated altered expressions of particular subunits in diverse human diseases, especially cancer. However a systematic study deciphering the transcriptional expression of the Mediator across different cancer entities is still lacking.We therefore performed a comprehensive in silico cancer vs. benign analysis of the Mediator complex subunits (MEDs) for 20 tumor entities using Oncomine datasets. The transcriptional expression profiles across almost all cancer entities showed differentially expressed MEDs as compared to benign tissue. Differential expression of MED8 in renal cell carcinoma (RCC) and MED12 in lung cancer (LCa) were validated and further investigated by immunohistochemical staining on tissue microarrays containing large numbers of specimen. MED8 in clear cell RCC (ccRCC) associated with shorter survival and advanced TNM stage and showed higher expression in metastatic than primary tumors. In vitro, siRNA mediated MED8 knockdown significantly impaired proliferation and motility in ccRCC cell lines, hinting at a role for MED8 to serve as a novel therapeutic target in ccRCC. Taken together, our Mediator complex transcriptome proved to be a valid tool for identifying cancer-related shifts in Mediator complex composition, revealing that MEDs do exhibit cancer specific transcriptional expression profiles. PMID:27050271

  9. Gene Expression Profiling Analysis of Castration-Resistant Prostate Cancer

    PubMed Central

    Wang, Xuelei; Wen, Jiling; Li, Rongbing; Qiu, Guangming; Zhou, Lan; Wen, Xiaofei

    2015-01-01

    Background Prostate cancer is a global health issue. Usually, men with metastatic disease will progress to castration-resistant prostate cancer (CRPC). We aimed to identify the differentially expressed genes (DEGs) in tumor samples from non-castrated and castrated men from LNCaP Orthotopic xenograft models of prostate cancer and to study the mechanisms of CRPC. Material/Methods In this work, GSE46218 containing 4 samples from non-castrated men and 4 samples from castrated men was downloaded from Gene Expression Omnibus. We identified DEGs using limma Geoquery in R, the Robust Multi-array Average (RMA) method in Bioconductor, and Bias methods, followed by constructing an integrated regulatory network involving DEGs, miRNAs, and TFs using Cytoscape. Then, we analyzed network motifs of the integrated gene regulatory network using FANMOD. We selected regulatory modules corresponding to network motifs from the integrated regulatory network by Perl script. We preformed gene ontology (GO) and pathway enrichment analysis of DEGs in the regulatory modules using DAVID. Results We identified total 443 DEGs. We built an integrated regulatory network, found three motifs (motif 1, motif 2 and motif 3), and got two function modules (module 1 corresponded to motif 1, and module 2 corresponded to motif 2). Several GO terms (such as regulation of cell proliferation, positive regulation of macromolecule metabolic process, phosphorylation, and phosphorus metabolic process) and two pathways (pathway in cancer and Melanoma) were enriched. Furthermore, some significant DEGs (such as CAV1, LYN, FGFR3 and FGFR3) were related to CPRC development. Conclusions These genes might play important roles in the development and progression of CRPC. PMID:25592164

  10. 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

  11. Comprehensive genomic profiles of small cell lung cancer.

    PubMed

    George, Julie; Lim, Jing Shan; Jang, Se Jin; Cun, Yupeng; Ozretić, Luka; Kong, Gu; Leenders, Frauke; Lu, Xin; Fernández-Cuesta, Lynnette; Bosco, Graziella; Müller, Christian; Dahmen, Ilona; Jahchan, Nadine S; Park, Kwon-Sik; Yang, Dian; Karnezis, Anthony N; Vaka, Dedeepya; Torres, Angela; Wang, Maia Segura; Korbel, Jan O; Menon, Roopika; Chun, Sung-Min; Kim, Deokhoon; Wilkerson, Matt; Hayes, Neil; Engelmann, David; Pützer, Brigitte; Bos, Marc; Michels, Sebastian; Vlasic, Ignacija; Seidel, Danila; Pinther, Berit; Schaub, Philipp; Becker, Christian; Altmüller, Janine; Yokota, Jun; Kohno, Takashi; Iwakawa, Reika; Tsuta, Koji; Noguchi, Masayuki; Muley, Thomas; Hoffmann, Hans; Schnabel, Philipp A; Petersen, Iver; Chen, Yuan; Soltermann, Alex; Tischler, Verena; Choi, Chang-min; Kim, Yong-Hee; Massion, Pierre P; Zou, Yong; Jovanovic, Dragana; Kontic, Milica; Wright, Gavin M; Russell, Prudence A; Solomon, Benjamin; Koch, Ina; Lindner, Michael; Muscarella, Lucia A; la Torre, Annamaria; Field, John K; Jakopovic, Marko; Knezevic, Jelena; Castaños-Vélez, Esmeralda; Roz, Luca; Pastorino, Ugo; Brustugun, Odd-Terje; Lund-Iversen, Marius; Thunnissen, Erik; Köhler, Jens; Schuler, Martin; Botling, Johan; Sandelin, Martin; Sanchez-Cespedes, Montserrat; Salvesen, Helga B; Achter, Viktor; Lang, Ulrich; Bogus, Magdalena; Schneider, Peter M; Zander, Thomas; Ansén, Sascha; Hallek, Michael; Wolf, Jürgen; Vingron, Martin; Yatabe, Yasushi; Travis, William D; Nürnberg, Peter; Reinhardt, Christian; Perner, Sven; Heukamp, Lukas; Büttner, Reinhard; Haas, Stefan A; Brambilla, Elisabeth; Peifer, Martin; Sage, Julien; Thomas, Roman K

    2015-08-01

    We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer. PMID:26168399

  12. Comprehensive genomic profiles of small cell lung cancer

    PubMed Central

    George, Julie; Lim, Jing Shan; Jang, Se Jin; Cun, Yupeng; Ozretić, Luka; Kong, Gu; Leenders, Frauke; Lu, Xin; Fernández-Cuesta, Lynnette; Bosco, Graziella; Müller, Christian; Dahmen, Ilona; Jahchan, Nadine S.; Park, Kwon-Sik; Yang, Dian; Karnezis, Anthony N.; Vaka, Dedeepya; Torres, Angela; Wang, Maia Segura; Korbel, Jan O.; Menon, Roopika; Chun, Sung-Min; Kim, Deokhoon; Wilkerson, Matt; Hayes, Neil; Engelmann, David; Pützer, Brigitte; Bos, Marc; Michels, Sebastian; Vlasic, Ignacija; Seidel, Danila; Pinther, Berit; Schaub, Philipp; Becker, Christian; Altmüller, Janine; Yokota, Jun; Kohno, Takashi; Iwakawa, Reika; Tsuta, Koji; Noguchi, Masayuki; Muley, Thomas; Hoffmann, Hans; Schnabel, Philipp A.; Petersen, Iver; Chen, Yuan; Soltermann, Alex; Tischler, Verena; Choi, Chang-min; Kim, Yong-Hee; Massion, Pierre P.; Zou, Yong; Jovanovic, Dragana; Kontic, Milica; Wright, Gavin M.; Russell, Prudence A.; Solomon, Benjamin; Koch, Ina; Lindner, Michael; Muscarella, Lucia A.; la Torre, Annamaria; Field, John K.; Jakopovic, Marko; Knezevic, Jelena; Castaños-Vélez, Esmeralda; Roz, Luca; Pastorino, Ugo; Brustugun, Odd-Terje; Lund-Iversen, Marius; Thunnissen, Erik; Köhler, Jens; Schuler, Martin; Botling, Johan; Sandelin, Martin; Sanchez-Cespedes, Montserrat; Salvesen, Helga B.; Achter, Viktor; Lang, Ulrich; Bogus, Magdalena; Schneider, Peter M.; Zander, Thomas; Ansén, Sascha; Hallek, Michael; Wolf, Jürgen; Vingron, Martin; Yatabe, Yasushi; Travis, William D.; Nürnberg, Peter; Reinhardt, Christian; Perner, Sven; Heukamp, Lukas; Büttner, Reinhard; Haas, Stefan A.; Brambilla, Elisabeth; Peifer, Martin; Sage, Julien; Thomas, Roman K.

    2016-01-01

    We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer. PMID:26168399

  13. Mutational profiling of colorectal cancers with microsatellite instability

    PubMed Central

    Lin, Elaine I.; Tseng, Li-Hui; Gocke, Christopher D.; Reil, Stacy; Le, Dung T.; Azad, Nilofer S.; Eshleman, James R.

    2015-01-01

    Microsatellite instability (MSI) is caused by defective mismatch repair in 15–20% of colorectal cancers (CRCs). Higher mutation loads in tumors with mismatch repair deficiency can predict response to pembrolizumab, an anti-programmed death 1 (PD-1) immune checkpoint inhibitor. We analyzed the mutations in 113 CRCs without MSI (MSS) and 29 CRCs with MSI-High (MSI-H) using the 50-gene AmpliSeq cancer panel. Overall, MSI-H CRCs showed significantly higher mutations than MSS CRCs, including insertion/deletion mutations at repeat regions. MSI-H CRCs showed higher incidences of mutations in the BRAF, PIK3CA, and PTEN genes as well as mutations in the receptor tyrosine kinase families. While the increased mutations in BRAF and PTEN in MSI-H CRCs are well accepted, we also support findings of mutations in the mTOR pathway and receptor tyrosine kinase family genes. MSS CRCs showed higher incidences of mutations in the APC, KRAS and TP53 genes, confirming previous findings. NGS assays may be designed to detect driver mutations for targeted therapeutics and to identify tumors with high mutation loads for potential treatment with immune checkpoint blockade therapies. Further studies may be warranted to elucidate potential targeted therapeutics against mutations in the mTOR pathway and the receptor tyrosine kinase family in MSI-H CRCs as well as the benefit of anti-PD-1 immunotherapy in hypermutated MSS CRCs or other cancers. PMID:26517354

  14. Methylation profiling of 48 candidate genes in tumor and matched normal tissues from breast cancer patients.

    PubMed

    Li, Zibo; Guo, Xinwu; Wu, Yepeng; Li, Shengyun; Yan, Jinhua; Peng, Limin; Xiao, Zhi; Wang, Shouman; Deng, Zhongping; Dai, Lizhong; Yi, Wenjun; Xia, Kun; Tang, Lili; Wang, Jun

    2015-02-01

    Gene-specific methylation alterations in breast cancer have been suggested to occur early in tumorigenesis and have the potential to be used for early detection and prevention. The continuous increase in worldwide breast cancer incidences emphasizes the urgent need for identification of methylation biomarkers for early cancer detection and patient stratification. Using microfluidic PCR-based target enrichment and next-generation bisulfite sequencing technology, we analyzed methylation status of 48 candidate genes in paired tumor and normal tissues from 180 Chinese breast cancer patients. Analysis of the sequencing results showed 37 genes differentially methylated between tumor and matched normal tissues. Breast cancer samples with different clinicopathologic characteristics demonstrated distinct profiles of gene methylation. The methylation levels were significantly different between breast cancer subtypes, with basal-like and luminal B tumors having the lowest and the highest methylation levels, respectively. Six genes (ACADL, ADAMTSL1, CAV1, NPY, PTGS2, and RUNX3) showed significant differential methylation among the 4 breast cancer subtypes and also between the ER +/ER- tumors. Using unsupervised hierarchical clustering analysis, we identified a panel of 13 hypermethylated genes as candidate biomarkers that performed a high level of efficiency for cancer prediction. These 13 genes included CST6, DBC1, EGFR, GREM1, GSTP1, IGFBP3, PDGFRB, PPM1E, SFRP1, SFRP2, SOX17, TNFRSF10D, and WRN. Our results provide evidence that well-defined DNA methylation profiles enable breast cancer prediction and patient stratification. The novel gene panel might be a valuable biomarker for early detection of breast cancer. PMID:25636590

  15. Erratum: Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing.

    PubMed

    2015-01-01

    The author's email has been corrected in the publication of Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing. There was an error with the author, Jerry Zhou's, email. The author's email has been updated to: j.zhou@uws.edu.au from: jzho7551@mail.usyd.edu.au. PMID:26167960

  16. Dynamic BH3 profiling-poking cancer cells with a stick.

    PubMed

    Montero, Joan; Letai, Anthony

    2016-05-01

    The vast majority of efforts in precision medicine for cancer try to link static genetic information to tumor biology and from there predict clinical response. Dynamic BH3 profiling offers an alternative functional approach by measuring death signaling induced by specific drugs in tumors from patients ex vivo to predict clinical response. PMID:27314085

  17. Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines

    PubMed Central

    Coram, Marc A.; Reddy, Anupama; Deng, Glenn; Telli, Melinda L.; Advani, Ranjana H.; Carlson, Robert W.; Mollick, Joseph A.; Sheth, Shruti; Kurian, Allison W.; Ford, James M.; Stockdale, Frank E.; Quake, Stephen R.; Pease, R. Fabian; Mindrinos, Michael N.; Bhanot, Gyan; Dairkee, Shanaz H.; Davis, Ronald W.; Jeffrey, Stefanie S.

    2012-01-01

    Background To improve cancer therapy, it is critical to target metastasizing cells. Circulating tumor cells (CTCs) are rare cells found in the blood of patients with solid tumors and may play a key role in cancer dissemination. Uncovering CTC phenotypes offers a potential avenue to inform treatment. However, CTC transcriptional profiling is limited by leukocyte contamination; an approach to surmount this problem is single cell analysis. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery. Methodology/Principal Findings We purified CTCs using the MagSweeper, an immunomagnetic enrichment device that isolates live tumor cells from unfractionated blood. CTCs that met stringent criteria for further analysis were obtained from 70% (14/20) of primary and 70% (21/30) of metastatic breast cancer patients; none were captured from patients with non-epithelial cancer (n = 20) or healthy subjects (n = 25). Microfluidic-based single cell transcriptional profiling of 87 cancer-associated and reference genes showed heterogeneity among individual CTCs, separating them into two major subgroups, based on 31 highly expressed genes. In contrast, single cells from seven breast cancer cell lines were tightly clustered together by sample ID and ER status. CTC profiles were distinct from those of cancer cell lines, questioning the suitability of such lines for drug discovery efforts for late stage cancer therapy. Conclusions/Significance For the first time, we directly measured high dimensional gene expression in individual CTCs without the common practice of pooling such cells. Elevated transcript levels of genes associated with metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM, TGFß1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Our findings demonstrate that profiling CTCs

  18. 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

  19. Rapid detection and profiling of cancer cells in fine-needle aspirates

    PubMed Central

    Lee, Hakho; Yoon, Tae-Jong; Figueiredo, Jose-Luiz; Swirski, Filip K.; Weissleder, Ralph

    2009-01-01

    There is a growing need for fast, highly sensitive and quantitative technologies to detect and profile unaltered cells in biological samples. Technologies in current clinical use are often time consuming, expensive, or require considerable sample sizes. Here, we report a diagnostic magnetic resonance (DMR) sensor that combines a miniaturized NMR probe with targeted magnetic nanoparticles for detection and molecular profiling of cancer cells. The sensor measures the transverse relaxation rate of water molecules in biological samples in which target cells of interest are labeled with magnetic nanoparticles. We achieved remarkable sensitivity improvements over our prior DMR prototypes by synthesizing new nanoparticles with higher transverse relaxivity and by optimizing assay protocols. We detected as few as 2 cancer cells in 1-μL sample volumes of unprocessed fine-needle aspirates of tumors and profiled the expression of several cellular markers in <15 min. PMID:19620715

  20. 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. PMID:26052692

  1. Cell surface and secreted protein profiles of human thyroid cancer cell lines reveal distinct glycoprotein patterns.

    PubMed

    Arcinas, Arthur; Yen, Ten-Yang; Kebebew, Electron; Macher, Bruce A

    2009-08-01

    Cell surface proteins have been shown to be effective therapeutic targets. In addition, shed forms of these proteins and secreted proteins can serve as biomarkers for diseases, including cancer. Thus, identification of cell surface and secreted proteins has been a prime area of interest in the proteomics field. Most cell surface and secreted proteins are known to be glycosylated, and therefore, a proteomics strategy targeting these proteins was applied to obtain proteomic profiles from various thyroid cancer cell lines that represent the range of thyroid cancers of follicular cell origin. In this study, we oxidized the carbohydrates of secreted proteins and those on the cell surface with periodate and isolated them via covalent coupling to hydrazide resin. The glycoproteins obtained were identified from tryptic peptides and N-linked glycopeptides released from the hydrazide resin using two-dimensional liquid chromatography-tandem mass spectrometry in combination with the gas phase fractionation. Thyroid cancer cell lines derived from papillary thyroid cancer (TPC-1), follicular thyroid cancer (FTC-133), Hurthle cell carcinoma (XTC-1), and anaplastic thyroid cancer (ARO and DRO-1) were evaluated. An average of 150 glycoproteins were identified per cell line, of which more than 57% are known cell surface or secreted glycoproteins. The usefulness of the approach for identifying thyroid cancer associated biomarkers was validated by the identification of glycoproteins (e.g., CD44, galectin 3 and metalloproteinase inhibitor 1) that have been found to be useful markers for thyroid cancer. In addition to glycoproteins that are commonly expressed by all of the cell lines, we identified others that are only expressed in the more well-differentiated thyroid cancer cell lines (follicular, Hurthle cell and papillary), or by cell lines derived from undifferentiated tumors that are uniformly fatal forms of thyroid cancer (i.e., anaplastic). On the basis of the results obtained, a

  2. Enrichment of CD44 in basal-type breast cancer correlates with EMT, cancer stem cell gene profile, and prognosis

    PubMed Central

    Xu, Hanxiao; Tian, Yijun; Yuan, Xun; Liu, Yu; Wu, Hua; Liu, Qian; Wu, Gen Sheng; Wu, Kongming

    2016-01-01

    Cluster of differentiation 44 (CD44) is a transmembrane glycoprotein that serves as the receptor for the extracellular matrix component hyaluronic acid. CD44 has been reported to play key roles in cell proliferation, motility, and survival, but its role in breast cancer remains controversial. In this study, we conducted a meta-analysis. A total of 23 published Gene Expression Omnibus databases were included to evaluate the association between CD44 mRNA expression and clinicopathological characteristics or prognosis of the patients with breast cancer. Our analysis revealed that CD44 expression was associated with clinicopathological features, including the histological grade, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor-2 status. Higher levels of CD44 expression were observed in the basal subtype of breast cancer both at the mRNA and protein levels (odds ratio [OR] =2.08, 95% confidence interval [CI]: 1.72–2.52; OR =2.11, 95% CI: 1.67–2.68). Patients with CD44 overexpression exhibited significantly worse overall survival (hazard ratio =1.27; 95% CI: 1.04–1.55). Whole gene profile analysis revealed that CD44 expression was enriched in basal-type breast cancer and correlated with epithelial–mesenchymal transition and cancer stem cell gene profiles. In summary, our analyses indicated that CD44 potentially might be a prognostic marker for breast cancer and thus can serve as a therapeutic target for basal-type breast cancer. PMID:26855592

  3. Gene Expression Profiling of Breast Cancer Brain Metastasis.

    PubMed

    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

  4. 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

  5. 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. PMID:27548261

  6. 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

  7. Automated tumor analysis for molecular profiling in lung cancer.

    PubMed

    Hamilton, Peter W; Wang, Yinhai; 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

    2015-09-29

    The discovery and clinical application of molecular biomarkers in solid tumors, increasingly relies on nucleic acid extraction from FFPE tissue sections and subsequent molecular profiling. This in turn requires the pathological review of haematoxylin & eosin (H&E) stained slides, to ensure sample quality, tumor DNA sufficiency by visually estimating the percentage tumor nuclei and tumor annotation for manual macrodissection. In this study on NSCLC, we demonstrate considerable variation in tumor nuclei percentage between pathologists, potentially undermining the precision of NSCLC molecular evaluation and emphasising the need for quantitative tumor evaluation. We subsequently describe the development and validation of a system called TissueMark for automated tumor annotation and percentage tumor nuclei measurement in NSCLC using computerized image analysis. Evaluation of 245 NSCLC slides showed precise automated tumor annotation of cases using Tissuemark, strong concordance with manually drawn boundaries and identical EGFR mutational status, following manual macrodissection from the image analysis generated tumor boundaries. Automated analysis of cell counts for % tumor measurements by Tissuemark showed reduced variability and significant correlation (p < 0.001) with benchmark tumor cell counts. This study demonstrates a robust image analysis technology that can facilitate the automated quantitative analysis of tissue samples for molecular profiling in discovery and diagnostics. PMID:26317646

  8. 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

  9. Can home care maintain an acceptable quality of life for patients with terminal cancer and their relatives?

    PubMed

    Hinton, J

    1994-01-01

    This prospective study was designed to assess whether patients with terminal cancer, and their relatives, find that competent home care sufficiently maintains comfort and helps adjustment. A random sample from a home care service with readily available beds comprised 77 adults and their relatives who were able and willing to be interviewed separately each week. They were asked the nature and degree of current problems and regular assessments were made of some qualities of life including mood, attitude to the condition, perceived help and preferred place of care. These patients had 90% of their care at home; 29% died at home but 30% were finally admitted for one to three days and 41% for longer. In the final eight weeks, tolerable physical symptoms were volunteered by a mean of 63% each week and psychological symptoms by 17%. Some distress was felt by 11% of patients; this was usually from pain, depression, dyspnoea, anxiety or weakness, and generally did not persist. Relatives suffered grief, strain or their own ill health. Patients' and relatives' reports generally matched except for the strain on carers. Regular assessments found that 64% of patients thought death certain or probable, and 27% thought it possible. Various proportions coped by optimism, fighting their disease, partial suppression or denial, but 50% reached positive acceptance. Relatives were more aware and accepting. About three-quarters of patients and half the relatives were composed, often enjoying life. Serious depression affected 5% of patients and anxiety 4%, but relatives' manifest depression in the later stages increased to 17% and anxiety to 14%. Many consciously disguised their feelings. Treatment was usually praised but realistic preference for home care fell steadily from 100% to 54% of patients and 45% of relatives. At follow-up most relatives approved of where patients had received care and died. PMID:7952369

  10. Large-Scale Profiling of Kinase Dependencies in Cancer Cell Lines.

    PubMed

    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

    2016-03-15

    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

  11. Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome.

    PubMed

    Jönsson, Jenny-Maria; Bartuma, Katarina; Dominguez-Valentin, Mev; Harbst, Katja; Ketabi, Zohreh; Malander, Susanne; Jönsson, Mats; Carneiro, Ana; Måsbäck, Anna; Jönsson, Göran; Nilbert, Mef

    2014-12-01

    Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified for histologic subtype, hierarchical clustering confirmed distinct differences related to heredity in the endometrioid and serous subtypes. Furthermore, separate clustering was achieved in an independent, publically available data set. The distinct genetic signatures in Lynch syndrome-associated and sporadic ovarian cancers point to alternative preferred tumorigenic routes and suggest that genetic discriminators may be relevant for molecular diagnostics and targeted therapeutics. PMID:24848881

  12. 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

  13. 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.

  14. Whole genome expression profiling in chewing-tobacco-associated oral cancers: a pilot study.

    PubMed

    Chakrabarti, Sanjukta; Multani, Shaleen; Dabholkar, Jyoti; Saranath, Dhananjaya

    2015-03-01

    The current study was undertaken with a view to identify differential biomarkers in chewing-tobacco-associated oral cancer tissues in patients of Indian ethnicity. The gene expression profile was analyzed in oral cancer tissues as compared to clinically normal oral buccal mucosa. We examined 30 oral cancer tissues and 27 normal oral tissues with 16 paired samples from contralateral site of the patient and 14 unpaired samples from different oral cancer patients, for whole genome expression using high-throughput IlluminaSentrix Human Ref-8 v2 Expression BeadChip array. The cDNA microarray analysis identified 425 differentially expressed genes with >1.5-fold expression in the oral cancer tissues as compared to normal tissues in the oral cancer patients. Overexpression of 255 genes and downregulation of 170 genes (p < 0.01) were observed. Further, a minimum twofold overexpression was observed in 32 genes and downregulation in 12 genes, in 30-83% of oral cancer patients. Biological pathway analysis using Kyoto Encyclopedia of Genes and Genome Pathway database revealed that the differentially regulated genes were associated with critical biological functions. The biological functions and representative deregulated genes include cell proliferation (AIM2, FAP, TNFSF13B, TMPRSS11A); signal transduction (FOLR2, MME, HTR3B); invasion and metastasis (SPP1, TNFAIP6, EPHB6); differentiation (CLEC4A, ELF5); angiogenesis (CXCL1); apoptosis (GLIPR1, WISP1, DAPL1); and immune responses (CD300A, IFIT2, TREM2); and metabolism (NNMT; ALDH3A1). Besides, several of the genes have been differentially expressed in human cancers including oral cancer. Our data indicated differentially expressed genes in oral cancer tissues and may identify prognostic and therapeutic biomarkers in oral cancers, postvalidation in larger numbers and varied population samples. PMID:25663065

  15. Gene Profile Identifies Zinc Transporters Differentially Expressed in Normal Human Organs and Human Pancreatic Cancer

    PubMed Central

    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.

    2013-01-01

    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. PMID:23331012

  16. 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.

  17. Profiles of Basal and stimulated receptor signaling networks predict drug response in breast cancer lines.

    PubMed

    Niepel, Mario; Hafner, Marc; Pace, Emily A; Chung, Mirra; Chai, Diana H; Zhou, Lili; Schoeberl, Birgit; Sorger, Peter K

    2013-09-24

    Identifying factors responsible for variation in drug response is essential for the effective use of targeted therapeutics. We profiled signaling pathway activity in a collection of breast cancer cell lines before and after stimulation with physiologically relevant ligands, which revealed the variability in network activity among cells of known genotype and molecular subtype. Despite the receptor-based classification of breast cancer subtypes, we found that the abundance and activity of signaling proteins in unstimulated cells (basal profile), as well as the activity of proteins in stimulated cells (signaling profile), varied within each subtype. Using a partial least-squares regression approach, we constructed models that significantly predicted sensitivity to 23 targeted therapeutics. For example, one model showed that the response to the growth factor receptor ligand heregulin effectively predicted the sensitivity of cells to drugs targeting the cell survival pathway mediated by PI3K (phosphoinositide 3-kinase) and Akt, whereas the abundance of Akt or the mutational status of the enzymes in the pathway did not. Thus, basal and signaling protein profiles may yield new biomarkers of drug sensitivity and enable the identification of appropriate therapies in cancers characterized by similar functional dysregulation of signaling networks. PMID:24065145

  18. DNA Methylation Profile and Expression of Surfactant Protein A2 gene in Lung Cancer

    PubMed Central

    Grageda, Melissa; Silveyra, Patricia; Thomas, Neal J.; DiAngelo, Susan L.; Floros, Joanna

    2014-01-01

    Knowledge of the methylation profile of genes allow for the identification of biomarkers that may guide diagnosis and effective treatment of disease. Human surfactant protein A (SP-A) plays an important role in lung homeostasis and immunity, and is encoded by two genes (SFTPA1 and SFTPA2). The goal of this study was to identify differentially methylated CpG sites in the promoter region of the SFTPA2 gene in lung cancer tissue, and to determine the correlation between the promoter’s methylation profile and gene expression. For this, we collected 28 pairs of cancerous human lung tissue and adjacent non-cancerous (NC) lung tissue: 17 adenocarcinoma (AC), 9 squamous cell carcinoma (SCC), and 2 AC with SCC features, and we evaluated DNA methylation of the SFTPA2 promoter region by bisulfite conversion. Our results identified a higher methylation ratio in one CpG site of the SFTPA2 gene in cancerous tissue vs. NC tissue (0.36 vs. 0.11, p=0.001). When assessing AC samples, we also found cancerous tissues associated with a higher methylation ratio (0.43 vs. 0.10, p=0.02). In the SCC group, although cancerous tissue showed a higher methylation ratio (0.22 vs. 0.11), this difference was not statistically significant (p=0.35). Expression of SFTPA2 mRNA and total SP-A protein was significantly lower in cancer tissue when compared to adjacent NC tissue (p<0.001), and correlated with the hypermethylated status of a SFTPA2 CpG site in AC samples. The findings of this pilot study may hold promise for future use of SFTPA2 as a biomarker for the diagnosis of lung cancer. PMID:25514367

  19. Clinical profile and post-operative lifestyle changes in cancer and non-cancer patients with ostomy

    PubMed Central

    Anaraki, Fakhryalsadat; Vafaie, Mohamad; Behboo, Roobic; Maghsoodi, Nakisa; Esmaeilpour, Sahar

    2012-01-01

    Aim The aim of this was to investigate some clinical profiles and lifestyle changes in stoma patients. Background Stoma patients experienced multiple complications due to their ostomy formation. Patients and methods A cross-sectional study performed on 102 random samples of stoma patients. Any patient with adequate physical and mental capability to participate and having had an ostomy in place for at least 3 months was eligible to enter the study. Participants asked to answer study questions concerning age, sex, type of stoma, having permanent or temporary ostomy, underlying cause of stoma formation, type of cancers cause of stoma. Patient also questioned about some lifestyle changes because of stoma including: changing diet, sexual satisfaction (if sexually active after stoma formation), sense of depression, changing job, change clothing style. Results Colostomy was the most common type of stoma followed by ileostomy and urostomy. In 80.4% of patients under study the stoma was permanent. Most patients had a stoma because of cancer (77.5%), with colon cancer (41.2%) being the most common malignant diagnosis. The mean age of cancer patients (56.1±10.9) with stoma was significantly higher than non-cancer patients (44.7±12.9) (p < 0.05). A significant differences were found regarding to sexual satisfaction after stoma formation between the two groups (p < 0.05) and the cancer group was less sexually satisfied post-ostomy. Conclusion In conclusion, stoma formation can caused multiple problems for both cancer and non-cancer patients. Counseling of patient is an important component of care that could help stoma patients to adjust with new situations. PMID:24834234

  20. 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

  1. Prostate cancer cells home to bone using a novel in vivo model: modulation by the integrin antagonist GLPG0187.

    PubMed

    Reeves, Kimberley J; Hurrell, Jack E; Cecchini, Marco; van der Pluijm, Gabri; Down, Jenny M; Eaton, Colby L; Hamdy, Freddie; Clement-Lacroix, Philippe; Brown, Nicola J

    2015-04-01

    Micrometastasis is a barrier to the development of effective cancer therapies for prostate cancer metastasis to bone. The mechanisms remain incompletely characterised, primarily due to an inability to adequately monitor the initial metastatic events in vivo. This study aimed to establish a new model, allowing the tracking of prostate cancer cells homing to bone, and furthermore, to evaluate the response of this approach to therapeutic modulation, using the integrin antagonist GLPG0187. A single murine metatarsal was engrafted into a dorsal skinfold chamber implanted on a SCID mouse. Fluorescently-labeled human prostate (PC3-GFP) or oral (SCC4-GFP) cancer cells were administered via intracardiac (i.c) injection, with simultaneous daily GLPG0187 or vehicle-control treatment (i.p. 100 mg/kg/day) for the experimental duration. Metatarsal recordings were taken every 48 h for up to 4 weeks. Tissue was harvested and processed for microCT, multiphoton analysis, histology and immunohistochemistry. Cell viability, proliferation and migration in vitro were also quantified following treatment with GLPG0187. Metatarsals rapidly revascularised by inosculation with the host vasculature (day 5-7). PC3-GFP cells adhered to the microvascular endothelium and/or metatarsal matrix 3 days after administration, with adhesion maintained for the experimental duration. GLPG0187 treatment significantly (p < 0.05) reduced PC3 cell number within the metatarsal in vivo and reduced migration (p < 0.05) and proliferation (p < 0.05) but not cell viability in vitro. This new model allows evaluation of the early events of tumour-cell homing and localisation to the bone microenvironment, in addition to determining responses to therapeutic interventions. PMID:25156971

  2. 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

  3. 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

  4. Addressing Methodological Challenges in Large Communication Data Sets: Collecting and Coding Longitudinal Interactions in Home Hospice Cancer Care.

    PubMed

    Reblin, Maija; Clayton, Margaret F; John, Kevin K; Ellington, Lee

    2016-07-01

    In this article, we present strategies for collecting and coding a large longitudinal communication data set collected across multiple sites, consisting of more than 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 data sets 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, multisite 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 has 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

  5. Gene expression profiling of peripheral blood cells for early detection of breast cancer

    PubMed Central

    2010-01-01

    Introduction Early detection of breast cancer is key to successful treatment and patient survival. We have previously reported the potential use of gene expression profiling of peripheral blood cells for early detection of breast cancer. The aim of the present study was to refine these findings using a larger sample size and a commercially available microarray platform. Methods Blood samples were collected from 121 females referred for diagnostic mammography following an initial suspicious screening mammogram. Diagnostic work-up revealed that 67 of these women had breast cancer while 54 had no malignant disease. Additionally, nine samples from six healthy female controls were included. Gene expression analyses were conducted using high density oligonucleotide microarrays. Partial Least Squares Regression (PLSR) was used for model building while a leave-one-out (LOO) double cross validation approach was used to identify predictors and estimate their prediction efficiency. Results A set of 738 probes that discriminated breast cancer and non-breast cancer samples was identified. By cross validation we achieved an estimated prediction accuracy of 79.5% with a sensitivity of 80.6% and a specificity of 78.3%. The genes deregulated in blood of breast cancer patients are related to functional processes such as defense response, translation, and various metabolic processes, such as lipid- and steroid metabolism. Conclusions We have identified a gene signature in whole blood that classifies breast cancer patients and healthy women with good accuracy supporting our previous findings. PMID:20078854

  6. Discovery of Lung Cancer Biomarkers by Profiling the Plasma Proteome with Monoclonal Antibody Libraries*

    PubMed Central

    Guergova-Kuras, Mariana; Kurucz, István; Hempel, William; Tardieu, Nadège; Kádas, János; Malderez-Bloes, Carole; Jullien, Anne; Kieffer, Yann; Hincapie, Marina; Guttman, András; Csánky, Eszter; Dezső, Balázs; Karger, Barry L.; Takács, László

    2011-01-01

    A challenge in the treatment of lung cancer is the lack of early diagnostics. Here, we describe the application of monoclonal antibody proteomics for discovery of a panel of biomarkers for early detection (stage I) of non-small cell lung cancer (NSCLC). We produced large monoclonal antibody libraries directed against the natural form of protein antigens present in the plasma of NSCLC patients. Plasma biomarkers associated with the presence of lung cancer were detected via high throughput ELISA. Differential profiling of plasma proteomes of four clinical cohorts, totaling 301 patients with lung cancer and 235 healthy controls, identified 13 lung cancer-associated (p < 0.05) monoclonal antibodies. The monoclonal antibodies recognize five different cognate proteins identified using immunoprecipitation followed by mass spectrometry. Four of the five antigens were present in non-small cell lung cancer cells in situ. The approach is capable of generating independent antibodies against different epitopes of the same proteins, allowing fast translation to multiplexed sandwich assays. Based on these results, we have verified in two independent clinical collections a panel of five biomarkers for classifying patient disease status with a diagnostics performance of 77% sensitivity and 87% specificity. Combining CYFRA, an established cancer marker, with the panel resulted in a performance of 83% sensitivity at 95% specificity for stage I NSCLC. PMID:21947365

  7. Discovery of lung cancer biomarkers by profiling the plasma proteome with monoclonal antibody libraries.

    PubMed

    Guergova-Kuras, Mariana; Kurucz, István; Hempel, William; Tardieu, Nadège; Kádas, János; Malderez-Bloes, Carole; Jullien, Anne; Kieffer, Yann; Hincapie, Marina; Guttman, András; Csánky, Eszter; Dezso, Balázs; Karger, Barry L; Takács, László

    2011-12-01

    A challenge in the treatment of lung cancer is the lack of early diagnostics. Here, we describe the application of monoclonal antibody proteomics for discovery of a panel of biomarkers for early detection (stage I) of non-small cell lung cancer (NSCLC). We produced large monoclonal antibody libraries directed against the natural form of protein antigens present in the plasma of NSCLC patients. Plasma biomarkers associated with the presence of lung cancer were detected via high throughput ELISA. Differential profiling of plasma proteomes of four clinical cohorts, totaling 301 patients with lung cancer and 235 healthy controls, identified 13 lung cancer-associated (p < 0.05) monoclonal antibodies. The monoclonal antibodies recognize five different cognate proteins identified using immunoprecipitation followed by mass spectrometry. Four of the five antigens were present in non-small cell lung cancer cells in situ. The approach is capable of generating independent antibodies against different epitopes of the same proteins, allowing fast translation to multiplexed sandwich assays. Based on these results, we have verified in two independent clinical collections a panel of five biomarkers for classifying patient disease status with a diagnostics performance of 77% sensitivity and 87% specificity. Combining CYFRA, an established cancer marker, with the panel resulted in a performance of 83% sensitivity at 95% specificity for stage I NSCLC. PMID:21947365

  8. From drug response profiling to target addiction scoring in cancer cell models.

    PubMed

    Yadav, Bhagwan; Gopalacharyulu, Peddinti; Pemovska, Tea; Khan, Suleiman A; Szwajda, Agnieszka; Tang, Jing; Wennerberg, Krister; Aittokallio, Tero

    2015-10-01

    Deconvoluting the molecular target signals behind observed drug response phenotypes is an important part of phenotype-based drug discovery and repurposing efforts. We demonstrate here how our network-based deconvolution approach, named target addiction score (TAS), provides insights into the functional importance of druggable protein targets in cell-based drug sensitivity testing experiments. Using cancer cell line profiling data sets, we constructed a functional classification across 107 cancer cell models, based on their common and unique target addiction signatures. The pan-cancer addiction correlations could not be explained by the tissue of origin, and only correlated in part with molecular and genomic signatures of the heterogeneous cancer cells. The TAS-based cancer cell classification was also shown to be robust to drug response data resampling, as well as predictive of the transcriptomic patterns in an independent set of cancer cells that shared similar addiction signatures with the 107 cancers. The critical protein targets identified by the integrated approach were also shown to have clinically relevant mutation frequencies in patients with various cancer subtypes, including not only well-established pan-cancer genes, such as PTEN tumor suppressor, but also a number of targets that are less frequently mutated in specific cancer types, including ABL1 oncoprotein in acute myeloid leukemia. An application to leukemia patient primary cell models demonstrated how the target deconvolution approach offers functional insights into patient-specific addiction patterns, such as those indicative of their receptor-type tyrosine-protein kinase FLT3 internal tandem duplication (FLT3-ITD) status and co-addiction partners, which may lead to clinically actionable, personalized drug treatment developments. To promote its application to the future drug testing studies, we have made available an open-source implementation of the TAS calculation in the form of a stand-alone R

  9. Multiparametric Biomechanical and Biochemical Phenotypic Profiling of Single Cancer Cells Using an Elasticity Microcytometer.

    PubMed

    Hu, Shuhuan; Liu, Guangyu; Chen, Weiqiang; Li, Xiang; Lu, Wei; Lam, Raymond H W; Fu, Jianping

    2016-05-01

    Deep phenotyping of single cancer cells is of critical importance in the era of precision medicine to advance understanding of relationships between gene mutation and cell phenotype and to elucidate the biological nature of tumor heterogeneity. Existing microfluidic single-cell phenotyping tools, however, are limited to phenotypic measurements of 1-2 selected morphological and physiological features of single cells. Herein a microfluidic elasticity microcytometer is reported for multiparametric biomechanical and biochemical phenotypic profiling of free-floating, live single cancer cells for quantitative, simultaneous characterizations of cell size, cell deformability/stiffness, and surface receptors. The elasticity microcytometer is implemented for measurements and comparisons of four human cell lines with distinct metastatic potentials and derived from different human tissues. An analytical model is developed from first principles for the first time to convert cell deformation and adhesion information of single cancer cells encapsulated inside the elasticity microcytometer to cell deformability/stiffness and surface protein expression. Together, the elasticity microcytometer holds great promise for comprehensive molecular, cellular, and biomechanical phenotypic profiling of live cancer cells at the single cell level, critical for studying intratumor cellular and molecular heterogeneity using low-abundance, clinically relevant human cancer cells. PMID:26929029

  10. DNA Methylome of Familial Breast Cancer Identifies Distinct Profiles Defined by Mutation Status

    PubMed Central

    Flanagan, James M.; Cocciardi, Sibylle; Waddell, Nic; Johnstone, Cameron N.; Marsh, Anna; Henderson, Stephen; Simpson, Peter; da Silva, Leonard; Khanna, Kumkum; Lakhani, Sunil; Boshoff, Chris; Chenevix-Trench, Georgia

    2010-01-01

    It is now understood that epigenetic alterations occur frequently in sporadic breast carcinogenesis, but little is known about the epigenetic alterations associated with familial breast tumors. We performed genome-wide DNA-methylation profiling on familial breast cancers (n = 33) to identify patterns of methylation specific to the different mutation groups (BRCA1, BRCA2, and BRCAx) or intrinsic subtypes of breast cancer (basal, luminal A, luminal B, HER2-amplified, and normal-like). We used methylated DNA immunoprecipitation (MeDIP) on Affymetrix promoter chips to interrogate methylation profiles across 25,500 distinct transcripts. Using a support vector machine classification algorithm, we demonstrated that genome-wide methylation profiles predicted tumor mutation status with estimated error rates of 19% (BRCA1), 31% (BRCA2), and 36% (BRCAx) but did not accurately predict the intrinsic subtypes defined by gene expression. Furthermore, using unsupervised hierarchical clustering, we identified a distinct subgroup of BRCAx tumors defined by methylation profiles. We validated these findings in the 33 tumors in the test set, as well as in an independent validation set of 47 formalin-fixed, paraffin-embedded familial breast tumors, by pyrosequencing and Epityper. Finally, gene-expression profiling and SNP CGH array previously performed on the same samples allowed full integration of methylation, gene-expression, and copy-number data sets, revealing frequent hypermethylation of genes that also displayed loss of heterozygosity, as well as of genes that show copy-number gains, providing a potential mechanism for expression dosage compensation. Together, these data show that methylation profiles for familial breast cancers are defined by the mutation status and are distinct from the intrinsic subtypes. PMID:20206335

  11. [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. PMID:25293794

  12. Profiling analysis of circulating microRNA expression in cervical cancer

    PubMed Central

    NAGAMITSU, YUZO; NISHI, HIROTAKA; SASAKI, TORU; TAKAESU, YOTARO; TERAUCHI, FUMITOSHI; ISAKA, KEIICHI

    2016-01-01

    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. 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. PMID:24917360

  15. Home kitchen ventilation, cooking fuels, and lung cancer risk in a prospective cohort of never smoking women in Shanghai, China

    PubMed Central

    Kim, Christopher; Gao, Yu-Tang; Xiang, Yong-Bing; Barone-Adesi, Francesco; Zhang, Yawei; Hosgood, H. Dean; Ma, Shuangge; Shu, Xiao-ou; Ji, Bu-Tian; Chow, Wong-Ho; Seow, Wei Jie; Bassig, Bryan; Cai, Qiuyin; Zheng, Wei; Rothman, Nathaniel; Lan, Qing

    2014-01-01

    Indoor air pollution (IAP) caused by cooking has been associated with lung cancer risk in retrospective case-control studies in developing and rural countries. We report the association of cooking conditions, fuel use, oil use and risk of lung cancer in a developed urban population in a prospective cohort of women in Shanghai. A total of 71,320 never smoking women were followed from 1996 through 2009 and 429 incident lung cancer cases were identified. Questionnaires collected information on household living and cooking practices for the women’s three most recent residences and utilization of cooking fuel and oil, and ventilation conditions. Cox proportional hazards regression estimated the association for kitchen ventilation conditions, cooking fuels, and use of cooking oils for the risk of lung cancer by hazard ratios (HR) with 95% confidence intervals (95% CI). Ever poor kitchen ventilation was associated with a 49% increase in lung cancer risk (HR: 1.49; 95% CI: 1.15–1.95) compared to never poor ventilation. Ever use of coal was not significantly associated. However, ever coal use with poor ventilation (HR: 1.69; 95% CI: 1.22–2.35) and twenty or more years of using coal (HR: 2.03; 95% CI: 1.35–3.05) was significantly associated compared to no exposure to coal or poor ventilation. Cooking oil use was not significantly associated. These results demonstrate that IAP from poor ventilation of coal combustion increases the risk of lung cancer and is an important public health issue in cities across China where people may have lived in homes with inadequate kitchen ventilation. PMID:24917360

  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. 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. PMID:26174441

  18. 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.

  19. 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

  20. 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

  1. Proteomic profiling of small-molecule inhibitors reveals dispensability of MTH1 for cancer cell survival.

    PubMed

    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

  2. Expression profiling of prostate cancer tissue delineates genes associated with recurrence after prostatectomy

    PubMed Central

    Mortensen, Martin Mørck; Høyer, Søren; Lynnerup, Anne-Sophie; Ørntoft, Torben Falck; Sørensen, Karina Dalsgaard; Borre, Michael; Dyrskjøt, Lars

    2015-01-01

    Prostate cancer is a leading cause of cancer death amongst males. The main clinical dilemma in treating prostate cancer is the high number of indolent cases that confer a significant risk of overtreatment. In this study, we have performed gene expression profiling of tumor tissue specimens from 36 patients with prostate cancer to identify transcripts that delineate aggressive and indolent cancer. Key genes were validated using previously published data and by tissue microarray analysis. Two molecular subgroups were identified with a significant overrepresentation of tumors from patients with biochemical recurrence in one of the groups. We successfully validated key transcripts association with recurrence using two publically available datasets totaling 669 patients. Twelve genes were found to be independent predictors of recurrence in multivariate logistical regression analysis. SFRP4 gene expression was consistently up regulated in patients with recurrence in all three datasets. Using an independent cohort of 536 prostate cancer patients we showed SFRP4 expression to be an independent predictor of recurrence after prostatectomy (HR = 1.35; p = 0.009). We identified SFRP4 to be associated with disease recurrence. Prospective studies are needed in order to assess the clinical usefulness of the identified key markers in this study. PMID:26522007

  3. 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

  4. Profiling cell-free and circulating miRNA: a clinical diagnostic tool for different cancers.

    PubMed

    Chakraborty, Chiranjib; Das, Srijit

    2016-05-01

    Effective cancer management depends on early diagnosis and treatment. There are several microRNAs (miRNAs) which are used for detection of various cancers. Cell-free and circulating miRNAs originate from plasma, either from blood cells or endothelial cells. Cell-free and circulating miRNAs are very much important in the diagnosis and prognosis of cancer therapy. Admittedly, biological knowledge of extracellular miRNAs is still at its preliminary level. Recent discoveries of novel cell-free and circulating miRNAs from the body fluids are now being considered as important biomarkers that may help us in the early diagnosis of any cancer. In the present review, we highlight the biogenesis of miRNAs and their current extracellular pattern, the discovery of circulating miRNA, significant advantages, and different profiling techniques. Finally, we discuss the different circulating miRNAs such as miR-21, miR-20a, miR-155, miR‑221, miR-210, miR-218, miR-200-family, miR-141, miR-122, miR-486-5p, miR‑423-5p, miR-29a, and miR-500 for clinical diagnosis of various cancers. The present review may be beneficial for future researches concerned with miRNAs which are used for detection of various cancers. PMID:26831657

  5. 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

  6. A decade of cancer gene profiling: from molecular portraits to molecular function.

    PubMed

    Sara, Henri; Kallioniemi, Olli; Nees, Matthias

    2010-01-01

    Cancer gene profiling has greatly profited from the progress in high-throughput technologies, including microarray-, sequencing-, and bioinformatics-based methods. The flood of data generated during the last decade has provoked a panel of "-omics" fields that significantly changed our understanding of malignant diseases. However, while the terms "-omics" and "-ome" in principle refer to the completeness of a genetic approach, we are in fact far from a complete understanding of cancer progression. We may understand gene expression patterns better and successfully use gene signatures for outcome prediction and prognosis, but truly promising molecular targets still have to find their way into novel therapeutic concepts. In this chapter, we will show how more comprehensive strategies, integrating multiple layers of genetic information, might in the future provide a more profound functional understanding of cancer. PMID:19882258

  7. Computational dissection of tissue contamination for identification of colon cancer-specific expression profiles.

    PubMed

    Türeci, Ozlem; Ding, Jiayi; Hilton, Holly; Bian, Hongjin; Ohkawa, Hitomi; Braxenthaler, Michael; Seitz, Gerhard; Raddrizzani, Laura; Friess, Helmut; Buchler, Markus; Sahin, Ugur; Hammer, Juergen

    2003-03-01

    Microarray profiles of bulk tumor tissues reflect gene expression corresponding to malignant cells as well as to many different types of contaminating normal cells. In this report, we assess the feasibility of querying baseline multitissue transcriptome databases to dissect disease-specific genes. Using colon cancer as a model tumor, we show that the application of Boolean operators (AND, OR, BUTNOT) for database searches leads to genes with expression patterns of interest. The BUTNOT operator for example allows the assignment of "expression signatures" to normal tissue specimens. These expression signatures were then used to computationally identify contaminating cells within conventionally dissected tissue specimens. The combination of several logic operators together with an expression database based on multiple human tissue specimens can resolve the problem of tissue contamination, revealing novel cancer-specific gene expression. Several markers, previously not known to be colon cancer associated, are provided. PMID:12631577

  8. Mass Spectrometry-Based Metabolomics Identifies Longitudinal Urinary Metabolite Profiles Predictive of Radiation-Induced Cancer.

    PubMed

    Cook, John A; Chandramouli, Gadisetti V R; Anver, Miriam R; Sowers, Anastasia L; Thetford, Angela; Krausz, Kristopher W; Gonzalez, Frank J; Mitchell, James B; Patterson, Andrew D

    2016-03-15

    Nonlethal exposure to ionizing radiation (IR) is a public concern due to its known carcinogenic effects. Although latency periods for IR-induced neoplasms are relatively long, the ability to detect cancer as early as possible is highly advantageous for effective therapeutic intervention. Therefore, we hypothesized that metabolites in the urine from mice exposed to total body radiation (TBI) would predict for the presence of cancer before a palpable mass was detected. In this study, we exposed mice to 0 or 5.4 Gy TBI, collected urine samples periodically over 1 year, and assayed urine metabolites by using mass spectrometry. Longitudinal data analysis within the first year post-TBI revealed that cancers, including hematopoietic, solid, and benign neoplasms, could be distinguished by unique urinary signatures as early as 3 months post-TBI. Furthermore, a distinction among different types of malignancies could be clearly delineated as early as 3 months post-TBI for hematopoietic neoplasms, 6 months for solid neoplasms, and by 1 year for benign neoplasms. Moreover, the feature profile for radiation-exposed mice 6 months post-TBI was found to be similar to nonirradiated control mice at 18 months, suggesting that TBI accelerates aging. These results demonstrate that urine feature profiles following TBI can identify cancers in mice prior to macroscopic detection, with important implications for the early diagnosis and treatment. PMID:26880804

  9. Profiling alternatively spliced mRNA isoforms for prostate cancer classification

    PubMed Central

    Zhang, Chaolin; Li, Hai-Ri; Fan, Jian-Bing; Wang-Rodriguez, Jessica; Downs, Tracy; Fu, Xiang-Dong; Zhang, Michael Q

    2006-01-01

    Background Prostate cancer is one of the leading causes of cancer illness and death among men in the United States and world wide. There is an urgent need to discover good biomarkers for early clinical diagnosis and treatment. Previously, we developed an exon-junction microarray-based assay and profiled 1532 mRNA splice isoforms from 364 potential prostate cancer related genes in 38 prostate tissues. Here, we investigate the advantage of using splice isoforms, which couple transcriptional and splicing regulation, for cancer classification. Results As many as 464 splice isoforms from more than 200 genes are differentially regulated in tumors at a false discovery rate (FDR) of 0.05. Remarkably, about 30% of genes have isoforms that are called significant but do not exhibit differential expression at the overall mRNA level. A support vector machine (SVM) classifier trained on 128 signature isoforms can correctly predict 92% of the cases, which outperforms the classifier using overall mRNA abundance by about 5%. It is also observed that the classification performance can be improved using multivariate variable selection methods, which take correlation among variables into account. Conclusion These results demonstrate that profiling of splice isoforms is able to provide unique and important information which cannot be detected by conventional microarrays. PMID:16608523

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

    PubMed

    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

    2015-10-01

    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. PMID:25784292

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

    PubMed

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

    2016-08-01

    Despite the recent progress in RNA modification study, a comprehensive modification profile is still lacking for mammalian cells. Using a quantitative HPLC/MS/MS assay, we present here a study where RNA modifications are examined in term of the major RNA species. With paired slow- and fast-proliferating cell lines, distinct RNA modification profiles are first revealed for diverse RNA species. Compared to mRNAs, increased ribose and nucleobase modifications are shown for the highly-structured tRNAs and rRNAs, lending support to their contribution to the formation of high-order structures. This study also reveals a dynamic tRNA modification profile in the fast-proliferating cells. In addition to cultured cells, this unique tRNA profile has been further confirmed with endometrial cancers and their adjacent normal tissues. Taken together, the results indicate that tRNA is a actively regulated RNA species in the fast-proliferating cancer cells, and suggest that they may play a more active role in biological process than expected. PMID:27246735

  12. A geographical profile of the South African population as a basis for epidemiological cancer research.

    PubMed

    van der Merwe, I J

    1988-11-19

    Because people do not necessarily become ill proportionally, particular subgroups of the population are more susceptible to certain types of diseases than others. It is also essential to take spatial distribution and accessibility of the population into account when considering the optimal location of medical facilities. A geographical profile of the heterogeneous population of South Africa with regard to demographic and socioeconomic composition and urbanisation patterns is therefore presented. Analysis of the composition of the population by tabulating and mapping population census results reveals a complexity which arises from the diversity between the developed white profile and the developing black and coloured communities with their escalating numbers, relative youth and socio-economic backlog. Examination of the maps shows up an unbalanced spatial urbanisation profile with overconcentration in the five metropolitan core areas. Although such a population framework usually fits best to cancer epidemiology, most other diseases could benefit from such an approach. PMID:3187804

  13. Rapid and comprehensive 'shotgun' lipidome profiling of colorectal cancer cell derived exosomes.

    PubMed

    Lydic, Todd A; Townsend, Steven; Adda, Christopher G; Collins, Christine; Mathivanan, Suresh; Reid, Gavin E

    2015-10-01

    There is an increasing recognition of the role that cancer cell derived exosomes play in intercellular signaling upon fusion or uptake with a target cell, including immune system evasion, tumor growth and metastasis. To date, however, although exosomal membrane and cargo lipids are expected to play a pivotal role in exosome biogenesis and secretion, as well as in fusion or uptake and target cell functional response, the detailed characterization of cancer cell derived exosome lipids across a range of different cancers has not yet been broadly explored. Here, a simple and straightforward lipidome analysis strategy consisting of optimized sample extraction and novel sample derivatization techniques, coupled with high-resolution 'shotgun' mass spectrometry and 'targeted' tandem mass spectrometry methods, is demonstrated for the rapid identification of >520 individual lipids in 36 lipid classes and sub classes from exosomes secreted by the colorectal cancer cell line, LIM1215. Relative quantification and comparison of exosome versus cellular lipid profiles reveals significant enrichment of certain lipid classes, as well as substantial lipid subclass remodeling and changes in abundance of individual lipids, including sphingolipids, sterol lipids, glycerolipids and glycerophospholipids, and particularly plasmalogen- and alkyl ether-containing glycerophospholipids. This analysis strategy therefore provides a platform for comprehensive lipidome profiling across a wide range of cancer cell or tissue derived exosomes, that will facilitate subsequent functional studies aimed at elucidating the role of specific cellular or exosome lipids in the onset and progression of colorectal cancer, or to identify specific lipid(s) that could serve as effective diagnostic or prognostic disease biomarkers. PMID:25907253

  14. Symptoms, unbearability and the nature of suffering in terminal cancer patients dying at home: a prospective primary care study

    PubMed Central

    2013-01-01

    Background Primary care physicians provide palliative home care. In cancer patients dying at home in the Netherlands (45% of all cancer patients) euthanasia in about one out of every seven patients indicates unbearable suffering. Symptom prevalence, relationship between intensity of symptoms and unbearable suffering, evolvement of symptoms and unbearability over time and quality of unbearable suffering were studied in end-of-life cancer patients in primary care. Methods 44 general practitioners during three years recruited cancer patients estimated to die within six months. Every two months patients quantified intensity as well as unbearability of 69 symptoms with the State-of-Suffering-V (SOS-V). Also overall unbearable suffering was quantified. The five-point rating scale ranged from 1 (not at all) to 5 (hardly can be worse). For symptoms assessed to be unbearable the nature of the suffering was additionally investigated with open-ended questions. The final interviews were analyzed; for longitudinal evolvement also the pre-final interviews were analyzed. Symptom intensity scores 4 and 5 were defined to indicate high intensity. Symptom unbearability scores 4 and 5 were defined to indicate unbearable suffering. Two raters categorized the qualitative descriptions of unbearable suffering. Results Out of 148 requested patients 51% participated; 64 patients were followed up until death. The SOS-V was administered at least once in 60 patients (on average 30 days before death) and at least twice in 33 patients. Weakness was the most frequent unbearable symptom (57%). Pain was unbearable in 25%. Pain, loss of control over one’s life and fear of future suffering frequently were unbearable (89-92%) when symptom intensity was high. Loss of control over one’s life, vomiting and not being able to do important things frequently were unbearable (52-80%) when symptom intensity was low. Unbearable weakness significantly increased between pre-final and final interview. Physical

  15. Monitoring of changes in lipid profiles during PLK1 knockdown in cancer cells using DESI MS.

    PubMed

    Jayashree, Balasubramanyam; Srimany, Amitava; Jayaraman, Srinidhi; Bhutra, Anjali; Janakiraman, Narayanan; Chitipothu, Srujana; Krishnakumar, Subramanian; Baddireddi, Lakshmi Subhadra; Elchuri, Sailaja; Pradeep, Thalappil

    2016-08-01

    The importance of the polo-like kinase 1 (PLK1) gene is increasing substantially both as a biomarker and as a target for highly specific cancer therapy. This is due to its involvement in multiple points of cell progression and carcinogenesis. PLK1 inhibitors' efficacy in treating human cancers has been limited due to the lack of a specific targeting strategy. Here, we describe a method of targeted downregulation of PLK1 in cancer cells and the concomitant rapid detection of surface lipidomic perturbations using desorption electrospray ionization mass spectrometry (DESI MS). The efficient delivery of siRNA targeting PLK1 gene selectively to the cancer cells is achieved by targeting overexpressed cell surface epithelial cell adhesion molecule (EpCAM) by the EpDT3 aptamer. The chimeric aptamer (EpDT3-siPLK1) showed the knockdown of PLK1 gene expression and PLK1 protein levels by quantitative PCR and western blotting, respectively. The abundant surface lipids, phosphatidylcholines (PCs), such as PC(32:1) (m/z 754.6), PC(34:1) (m/z 782.6), and PC(36:2) (m/z 808.6), were highly expressed in MCF-7 and WERI-RB1 cancer cells compared to normal MIO-M1 cells and they were observed using DESI MS. These overexpressed cell surface lipids in the cancer cells were downregulated upon the treatment of EpDT3-siPLK1 chimera indicating a novel role of PLK1 to regulate surface lipid expression in addition to the efficient selective cancer targeting ability. Our results indicate that DESI MS has a potential ability to rapidly monitor aptamer-mediated cancer therapy and accelerate the drug discovery process. Graphical abstract Binding of aptamer chimera to the cells and changes in lipid profile. PMID:27277815

  16. Bladder Cancer Associated Gene Expression Signatures Identified by Profiling of Exfoliated Urothelia

    PubMed Central

    Rosser, Charles J.; Liu, Li; Sun, Yijun; Villicana, Patrick; McCullers, Molly; Porvasnik, Stacy; Young, Paul R.; Parker, Alexander S.; Goodison, Steve

    2009-01-01

    Bladder cancer is the fifth most commonly diagnosed malignancy in the United States and one of the most prevalent worldwide. It harbors a probability of recurrence of >50%, thus rigorous, long-term surveillance of patients is advocated. Flexible cystoscopy coupled with voided urine cytology (VUC) is the primary diagnostic approach, but cystoscopy is an uncomfortable, invasive procedure and the sensitivity of VUC is poor in all but high-grade tumors. Thus, improvements in non-invasive urinalysis assessment strategies would benefit patients. We applied gene expression microarray analysis to exfoliated urothelia recovered from bladder washes obtained prospectively from 46 patients with subsequently confirmed presence or absence of bladder cancer. Data from microarrays containing 56,000 targets was subjected to a panel of statistical analyses to identify bladder cancer-associated gene signatures. Hierarchical clustering and supervised learning algorithms were used to classify samples on the basis of tumor burden. A differentially expressed geneset of 319 gene probes was associated with the presence of bladder cancer (P<0.01), and visualization of protein interaction networks revealed VEGF and AGT as pivotal factors in tumor cells. Supervised machine learning and a cross-validation approach were used to build a 14-gene molecular classifier that was able to classify patients with and without bladder cancer with an overall accuracy of 76%. Our results show that it is possible to achieve the detection of bladder cancer using molecular signatures present in exfoliated tumor urothelia. Further investigation and validation of the cancer-associated profiles may reveal important biomarkers for the non-invasive detection and surveillance of bladder cancer. PMID:19190164

  17. 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

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

    PubMed

    Gilroy, Kathryn L; Terry, Anne; Naseer, Asif; de Ridder, Jeroen; Allahyar, Amin; Wang, Weiwei; Carpenter, Eric; Mason, Andrew; Wong, Gane K-S; Cameron, Ewan R; 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. Biological Functions of the Genes in the Mammaprint Breast Cancer Profile Reflect the Hallmarks of Cancer

    PubMed Central

    Tian, Sun; Roepman, Paul; van’t Veer, Laura J; Bernards, Rene; de Snoo, Femke; Glas, Annuska M

    2010-01-01

    Background: MammaPrint was developed as a diagnostic tool to predict risk of breast cancer metastasis using the expression of 70 genes. To better understand the tumor biology assessed by MammaPrint, we interpreted the biological functions of the 70-genes and showed how the genes reflect the six hallmarks of cancer as defined by Hanahan and Weinberg. Results: We used a bottom-up system biology approach to elucidate how the cellular processes reflected by the 70-genes work together to regulate tumor activities and progression. The biological functions of the genes were analyzed using literature research and several bioinformatics tools. Protein-protein interaction network analyses indicated that the 70-genes form highly interconnected networks and that their expression levels are regulated by key tumorigenesis related genes such as TP53, RB1, MYC, JUN and CDKN2A. The biological functions of the genes could be associated with the essential steps necessary for tumor progression and metastasis, and cover the six well-defined hallmarks of cancer, reflecting the acquired malignant characteristics of a cancer cell along with tumor progression and metastasis-related biological activities. Conclusion: Genes in the MammaPrint gene signature comprehensively measure the six hallmarks of cancer-related biology. This finding establishes a link between a molecular signature and the underlying molecular mechanisms of tumor cell progression and metastasis. PMID:21151591

  20. 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

  1. 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 ...

  2. 6 Common Cancers - Breast Cancer

    MedlinePlus

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

  3. 6 Common Cancers - Colorectal Cancer

    MedlinePlus

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

  4. 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 ( ...

  5. 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)

  6. Proteomic Profiling of Paraffin-Embedded Samples Identifies Metaplasia-Specific and Early-Stage Gastric Cancer Biomarkers

    PubMed Central

    Sousa, Josane F.; Ham, Amy-Joan L.; Whitwell, Corbin; Nam, Ki Taek; Lee, Hyuk-Joon; Yang, Han-Kwang; Kim, Woo Ho; Zhang, Bing; Li, Ming; LaFleur, Bonnie; Liebler, Daniel C.; Goldenring, James R.

    2013-01-01

    Early diagnosis and curative resection are the predominant factors associated with increased survival in patients with gastric cancer. However, most gastric cancer cases are still diagnosed at later stages. Since most pathologic specimens are archived as FFPE samples, the ability to use them to generate expression profiles can greatly improve cancer biomarker discovery. We sought to uncover new biomarkers for stomach preneoplastic metaplasias and neoplastic lesions by generating proteome profiles using FFPE samples. We combined peptide isoelectric focusing and liquid chromatography–tandem mass spectrometry analysis to generate proteomic profiles from FFPE samples of intestinal-type gastric cancer, metaplasia, and normal mucosa. The expression patterns of selected proteins were analyzed by immunostaining first in single tissue sections from normal stomach, metaplasia, and gastric cancer and later in larger tissue array cohorts. We detected 60 proteins up-regulated and 87 proteins down-regulated during the progression from normal mucosa to metaplasia to gastric cancer. Two of the up-regulated proteins, LTF and DMBT1, were validated as specific markers for spasmolytic polypeptide–expressing metaplasia and intestinal metaplasia, respectively. In cancers, significantly lower levels of DMBT1 or LTF correlated with more advanced disease and worse prognosis. Thus, proteomic profiling using FFPE samples has led to the identification of two novel markers for stomach metaplasias and gastric cancer prognosis. PMID:22944598

  7. 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...

  8. Insulin Receptor Substrate Adaptor Proteins Mediate Prognostic Gene Expression Profiles in Breast Cancer

    PubMed Central

    Becker, Marc A.; Ibrahim, Yasir H.; Oh, Annabell S.; Fagan, Dedra H.; Byron, Sara A.; Sarver, Aaron L.; Lee, Adrian V.; Shaw, Leslie M.; Fan, Cheng; Perou, Charles M.; Yee, Douglas

    2016-01-01

    Therapies targeting the type I insulin-like growth factor receptor (IGF-1R) have not been developed with predictive biomarkers to identify tumors with receptor activation. We have previously shown that the insulin receptor substrate (IRS) adaptor proteins are necessary for linking IGF1R to downstream signaling pathways and the malignant phenotype in breast cancer cells. The purpose of this study was to identify gene expression profiles downstream of IGF1R and its two adaptor proteins. IRS-null breast cancer cells (T47D-YA) were engineered to express IRS-1 or IRS-2 alone and their ability to mediate IGF ligand-induced proliferation, motility, and gene expression determined. Global gene expression signatures reflecting IRS adaptor specific and primary vs. secondary ligand response were derived (Early IRS-1, Late IRS-1, Early IRS-2 and Late IRS-2) and functional pathway analysis examined. IRS isoforms mediated distinct gene expression profiles, functional pathways, and breast cancer subtype association. For example, IRS-1/2-induced TGFb2 expression and blockade of TGFb2 abrogated IGF-induced cell migration. In addition, the prognostic value of IRS proteins was significant in the luminal B breast tumor subtype. Univariate and multivariate analyses confirmed that IRS adaptor signatures correlated with poor outcome as measured by recurrence-free and overall survival. Thus, IRS adaptor protein expression is required for IGF ligand responses in breast cancer cells. IRS-specific gene signatures represent accurate surrogates of IGF activity and could predict response to anti-IGF therapy in breast cancer. PMID:26991655

  9. Cancer Therapy Directed by Comprehensive Genomic Profiling: A Single Center Study.

    PubMed

    Wheler, Jennifer J; Janku, Filip; Naing, Aung; Li, Yali; Stephen, Bettzy; Zinner, Ralph; Subbiah, Vivek; Fu, Siqing; Karp, Daniel; Falchook, Gerald S; Tsimberidou, Apostolia M; Piha-Paul, Sarina; Anderson, Roosevelt; Ke, Danxia; Miller, Vincent; Yelensky, Roman; Lee, J Jack; Hong, David S; Kurzrock, Razelle

    2016-07-01

    Innovative molecular diagnostics deployed in the clinic enable new ways to stratify patients into appropriate treatment regimens. These approaches may resolve a major challenge for early-phase clinical trials, which is to recruit patients who, while having failed previous treatments, may nevertheless respond to molecularly targeted drugs. We report the findings of a prospective, single-center study conducted in patients with diverse refractory cancers who underwent comprehensive genomic profiling (CGP; next-generation sequencing, 236 genes). Of the 500 patients enrolled, 188 (37.6%) received either matched (N = 122/188, 65%) or unmatched therapy (N = 66/188, 35%). The most common reasons that patients were not evaluable for treatment included insufficient tissue, death, or hospice transfer. The median number of molecular alterations per patient was five (range, 1-14); median number of prior therapies, four. The most common diagnoses were ovarian cancer (18%), breast cancer (16%), sarcoma (13%), and renal cancer (7%). Of the 339 successfully profiled patients, 317 (93.5%) had at least one potentially actionable alteration. By calculating matching scores, based on the number of drug matches and genomic aberrations per patient, we found that high scores were independently associated with a greater frequency of stable disease ≥6 months/partial/complete remission [22% (high scores) vs. 9% (low scores), P = 0.024], longer time-to-treatment failure [hazard ratio (HR) = 0.52; 95% confidence interval (CI) = 0.36-0.74; P = 0.0003], and survival (HR = 0.65; 95% CI = 0.43-1.0; P = 0.05). Collectively, this study offers a clinical proof of concept for the utility of CGP in assigning therapy to patients with refractory malignancies, especially in those patients with multiple genomic aberrations for whom combination therapies could be implemented. Cancer Res; 76(13); 3690-701. ©2016 AACR. PMID:27197177

  10. 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. PMID:22923011

  11. Comprehensive Native Glycan Profiling with Isomer Separation and Quantitation for the Discovery of Cancer Biomarkers

    PubMed Central

    Hua, Serenus; An, Hyun Joo; Ozcan, Sureyya; Ro, Grace S.; Soares, Stephanie; DeVere-White, Ralph; Lebrilla, Carlito B.

    2012-01-01

    Glycosylation is highly sensitive to the biochemical environment and has been implicated in many diseases including cancer. Glycan compositional profiling of human serum with mass spectrometry has already identified potential biomarkers for several types of cancer and diseases; however, composition alone does not fully describe glycan stereo- and regioisomeric diversity. The vast structural heterogeneity of glycans presents a formidable analytical challenge. We have developed a method to identify and quantify isomeric native glycans using nanoflow liquid chromatography (nano-LC)/mass spectrometry. A microfluidic chip packed with graphitized carbon was used to chromatographically separate the glycans. To determine the utility of this method for structure-specific biomarker discovery, we analyzed serum samples from two groups of prostate cancer patients with different prognoses. More than 300 N-glycan species (including isomeric structures) were identified, corresponding to over 100 N-glycan compositions. Statistical tests established significant differences in glycan abundances between patient groups. This method provides comprehensive, selective, and quantitative glycan profiling. PMID:21776491

  12. 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

  13. 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. PMID:25926073

  14. Metabolomic profiling of human plasma in pancreatic cancer using pressurized capillary electrochromatography.

    PubMed

    Zhang, Huiping; Wang, Yan; Gu, Xue; Zhou, Junyi; Yan, Chao

    2011-02-01

    The application of pressurized capillary electrochromatography (pCEC) coupled with ultra violet (UV) detection has been investigated for the production of global metabolite profiles from human plasma, and its capabilities of classifying pancreatic cancer patients. The pCEC separation of plasma samples was performed on a RP column with gradient elution. The applied voltage, detection wavelength and type of acid modifiers on separation of plasma samples were optimized with pooled quality control (QC) sample. The stability and the repeatability of the methodology were also determined by the repeat analysis of QC sample. The effects of different scaling methods on the results of orthogonal partial least-squares discrimination analysis (OPLS-DA) based on pCEC-UV data set were also investigated. The results of the current study clearly showed the different phenotypes of metabolites of pancreatic cancer patients and healthy controls based on pCEC-UV plasma profiles. OPLS-DA data are shown to provide a valuable means of convenient classification. This work indicated that pCEC-UV method can be used as a cost-effective and information-rich, while relatively simple and inexpensive approach for plasma profiling on disease metabolomics studies. PMID:21298661

  15. Application of Molecular Profiling in Clinical Trials for Advanced Metastatic Cancers

    PubMed Central

    Williams, P. Mickey; Lih, Chih-Jian; Polley, Eric C.; Chen, Alice P.; Rubinstein, Larry V.; Zhao, Yingdong; Simon, Richard M.; Conley, Barbara A.; Doroshow, James H.

    2015-01-01

    There is growing interest in the application of molecular profiling, including sequencing, genotyping, and/or mRNA expression profiling, to the analysis of patient tumors with the objective of applying these data to inform therapeutic choices for patients with advanced cancers. Multiple clinical trials that are attempting to validate this personalized or precision medicine approach are in various stages of development and execution. Although preliminary data from some of these efforts have fueled excitement about the value and utility of these studies, their execution has also provoked many questions about the best way to approach complicating factors such as tumor heterogeneity and the choice of which genetic mutations to target. This commentary highlights some of the challenges confronting the clinical application of molecular tumor profiling and the various trial designs being utilized to address these challenges. Randomized trials that rigorously test patient response to molecularly targeted agents assigned based on the presence of a defined set of mutations in putative cancer-driving pathways are required to address some of the current challenges and to identify patients likely to benefit from this approach. PMID:25663694

  16. Proteomic profile of KSR1-regulated signalling in response to genotoxic agents in breast cancer.

    PubMed

    Zhang, Hua; Angelopoulos, Nicos; Xu, Yichen; Grothey, Arnhild; Nunes, Joao; Stebbing, Justin; Giamas, Georgios

    2015-06-01

    Kinase suppressor of Ras 1 (KSR1) has been implicated in tumorigenesis in multiple cancers, including skin, pancreatic and lung carcinomas. However, our recent study revealed a role of KSR1 as a tumour suppressor in breast cancer, the expression of which is potentially correlated with chemotherapy response. Here, we aimed to further elucidate the KSR1-regulated signalling in response to genotoxic agents in breast cancer. Stable isotope labelling by amino acids in cell culture (SILAC) coupled to high-resolution mass spectrometry (MS) was implemented to globally characterise cellular protein levels induced by KSR1 in the presence of doxorubicin or etoposide. The acquired proteomic signature was compared and GO-STRING analysis was subsequently performed to illustrate the activated functional signalling networks. Furthermore, the clinical associations of KSR1 with identified targets and their relevance in chemotherapy response were examined in breast cancer patients. We reveal a comprehensive repertoire of thousands of proteins identified in each dataset and compare the unique proteomic profiles as well as functional connections modulated by KSR1 after doxorubicin (Doxo-KSR1) or etoposide (Etop-KSR1) stimulus. From the up-regulated top hits, several proteins, including STAT1, ISG15 and TAP1 are also found to be positively associated with KSR1 expression in patient samples. Moreover, high KSR1 expression, as well as high abundance of these proteins, is correlated with better survival in breast cancer patients who underwent chemotherapy. In aggregate, our data exemplify a broad functional network conferred by KSR1 with genotoxic agents and highlight its implication in predicting chemotherapy response in breast cancer. PMID:26022350

  17. Serum and tissue profiling in bladder cancer combining protein and tissue arrays.

    PubMed

    Orenes-Piñero, Esteban; Barderas, Rodrigo; Rico, Daniel; Casal, J Ignacio; Gonzalez-Pisano, David; Navajo, Jose; Algaba, Ferran; Piulats, Josep Maria; Sanchez-Carbayo, Marta

    2010-01-01

    Aiming at identifying biomarkers for bladder cancer, the serum proteome was explored in a pilot study through a profiling approach using protein arrays. Supervised analyses identified a panel 171 immunogenic proteins differentially expressed between patients with bladder cancer (n = 12) and controls without the disease (n = 10). The microanatomical expression patterns of novel immunogenic proteins, especially dynamin and clusterin, were found significantly associated with histopathologic variables and overall survival, as confirmed by immunohistochemistry using an independent series of bladder tumors contained in tissue microarrays (n = 289). Thus, the protein arrays approach has identified a panel of immunogenic candidates that may potentially play a role as diagnostic biomarkers, especially for muscle invasive disease. Moreover, the protein expression patterns of dynamin and clusterin in bladder tumors were shown to adjunct for histopathologic staging and clinical outcome prognosis. PMID:19883059

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

    PubMed Central

    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. PMID:26618619

  19. Measurement of bioelectric and acoustic profile of breast tissue using hybrid magnetoacoustic method for cancer detection.

    PubMed

    Salim, M I Mohamad; Supriyanto, E; Haueisen, J; Ariffin, I; Ahmad, A H; Rosidi, B

    2013-04-01

    This paper proposes a novel hybrid magnetoacoustic measurement (HMM) system aiming at breast cancer detection. HMM combines ultrasound and magnetism for the simultaneous assessment of bioelectric and acoustic profiles of breast tissue. HMM is demonstrated on breast tissue samples, which are exposed to 9.8 MHz ultrasound wave with the presence of a 0.25 Tesla static magnetic field. The interaction between the ultrasound wave and the magnetic field in the breast tissue results in Lorentz Force that produces a magnetoacoustic voltage output, proportional to breast tissue conductivity. Simultaneously, the ultrasound wave is sensed back by the ultrasound receiver for tissue acoustic evaluation. Experiments are performed on gel phantoms and real breast tissue samples harvested from laboratory mice. Ultrasound wave characterization results show that normal breast tissue experiences higher attenuation compared with cancerous tissue. The mean magnetoacoustic voltage results for normal tissue are lower than that for the cancerous tissue group. In conclusion, the combination of acoustic and bioelectric measurements is a promising approach for breast cancer diagnosis. PMID:23238828

  20. Impact of molecular profiling on overall survival of patients with advanced ovarian cancer

    PubMed Central

    Herzog, Thomas J.; Spetzler, David; Xiao, Nick; Burnett, Ken; Maney, Todd; Voss, Andreas; Reddy, Sandeep; Burger, Robert; Krivak, Thomas; Powell, Matthew; Friedlander, Michael; McGuire, William

    2016-01-01

    Objective Patients with recurrent epithelial ovarian cancer (EOC) have limited treatment options. Studies have reported that biomarker profiling may help predict patient response to available treatments. This study sought to determine the value of biomarker profiling in recurrent EOC. Results Patients in the Matched cohort had a median OS of 36 months compared to 27 months for patients in the Unmatched cohort (HR 0.62, 95% CI 0.41-0.96; p < 0.03). Individual biomarkers were analyzed, with TUBB3, and PGP prognostic for survival. Biomarker analysis also identified a molecular subtype (positive for at least two of the following markers: ERCC1, RRM1, TUBB3, PGP) with particularly poor overall survival. Methods 224 patients from a commercial registry (NCT02678754) with stage IIIC/IV EOC at diagnosis, or restaged to IIIC/IV EOC at the time of molecular profiling, were retrospectively divided into two cohorts based on whether or not the drugs they received matched their profile recommendations. The Matched cohort received no drugs predicted to be lack-of-benefit while the Unmatched cohort received at least one drug predicted to be lack-of-benefit. Profile biomarker/drug associations were based on multiple test platforms including immunohistochemistry, fluorescent in situ hybridization and DNA sequencing. Conclusions This report demonstrates the ability of multi-platform molecular profiling to identify EOC patients at risk of inferior survival. It also suggests a potential beneficial role of avoidance of lack-of-benefit therapies which, when administered, resulted in decreased survival relative to patients who received only therapies predicted to be of benefit. PMID:26942886

  1. Plasma metabolomic profiles of breast cancer patients after short-term limonene intervention

    PubMed Central

    Miller, Jessica A.; Pappan, Kirk; Thompson, Patricia A.; Want, Elizabeth J.; Siskos, Alexandros; Keun, Hector C.; Wulff, Jacob; Hu, Chengcheng; Lang, Julie E.; Chow, H-H. Sherry

    2014-01-01

    Limonene is a lipophilic monoterpene found in high levels in citrus peel. Limonene demonstrates anti-cancer properties in preclinical models with effects on multiple cellular targets at varying potency. While of interest as a cancer chemopreventive, the biological activity of limonene in humans is poorly understood. We conducted metabolite profiling in 39 paired (pre/post-intervention) plasma samples from early-stage breast cancer patients receiving limonene treatment (2 g QD) before surgical resection of their tumor. Metabolite profiling was conducted using ultra-performance liquid chromatography (UPLC) coupled to a linear trap quadrupole (LTQ) system and gas chromatography mass spectrometry (GC-MS). Metabolites were identified by comparison of ion features in samples to a standard reference library. Pathway-based interpretation was conducted using the human metabolome database (HMDB) and the MetaCyc database. Of the 397 named metabolites identified, 72 changed significantly with limonene intervention. Class-based changes included significant decreases in adrenal steroids (P’s<0.01), and significant increases in bile acids (P’s≤0.05) and multiple collagen breakdown products (P’s<0.001). The pattern of changes also suggested alterations in glucose metabolism. There were 47 metabolites whose change with intervention was significantly correlated to a decrease in cyclin D1, a cell cycle regulatory protein, in patient tumor tissues (P’s≤0.05). Here, oral administration of limonene resulted in significant changes in several metabolic pathways. Further, pathway-based changes were related to the change in tissue level cyclin D1 expression. Future controlled clinical trials with limonene are necessary to determine the potential role and mechanisms of limonene in the breast cancer prevention setting. PMID:25388013

  2. Development and psychometric testing of a breast cancer patient-profiling questionnaire

    PubMed Central

    Gorini, Alessandra; Mazzocco, Ketti; Gandini, Sara; Munzone, Elisabetta; McVie, Gordon; Pravettoni, Gabriella

    2015-01-01

    Introduction The advent of “personalized medicine” has been driven by technological advances in genomics. Concentration at the subcellular level of a patient’s cancer cells has meant inevitably that the “person” has been overlooked. For this reason, we think there is an urgent need to develop a truly personalized approach focusing on each patient as an individual, assessing his/her unique mental dimensions and tailoring interventions to his/her individual needs and preferences. The aim of this study was to develop and test the psychometric properties of the ALGA-Breast Cancer (ALGA-BC), a new multidimensional questionnaire that assesses the breast cancer patient’s physical and mental characteristics in order to provide physicians, prior to the consultation, with a patient’s profile that is supposed to facilitate subsequent communication, interaction, and information delivery between the doctor and the patient. Methods The specific validation processes used were: content and face validity, construct validity using factor analysis, reliability and internal consistency using test–retest reliability, and Cronbach’s alpha correlation coefficient. The exploratory analysis included 100 primary breast cancer patients and 730 healthy subjects. Results The exploratory factor analysis revealed eight key factors: global self-rated health, perceived physical health, anxiety, self-efficacy, cognitive closure, memory, body image, and sexual life. Test–retest reliability and internal consistency were good. Comparing patients with a sample of healthy subjects, we also observed a general ability of the ALGA-BC questionnaire to discriminate between the two. Conclusion The ALGA-BC questionnaire with 29 items is a valid instrument with which to obtain a patient’s profile that is supposed to help physicians achieve meaningful personalized care which supplements biological and genetic analyses. PMID:26064067

  3. Home chemotherapy for children with cancer: perspectives from health care professionals.

    PubMed

    Stevens, Bonnie; McKeever, Patricia; Booth, Marilyn; Greenberg, Mark; Daub, Stacey; Gafni, Amiram; Gammon, Janet; Yamada, Janet; Beamer, Madelyn

    2004-03-01

    The goal of this study was to determine the perspectives of healthcare professionals (HPs) from community and hospital settings involved in a paediatric home chemotherapy programme. Using a prospective descriptive study design, HPs including paediatricians, community nurses, hospital clinic nurses, administrators and pharmacists were interviewed using a moderately structured open-ended approach. Through inductive content analysis, data were categorised under three themes reflecting HPs' perspectives on the programme: (1) perceived family benefits, (2) human resources and service delivery considerations and (3) impact on the role of the HP. All HPs reported that home chemotherapy helped reduce both disruption to family life and psychological stress. Community-based HPs reported increased job satisfaction, increased workload and increased frustration related to scheduling challenges. Hospital-based HPs reported decreased patient interaction and discrepancies in workload changes. Both groups emphasised the need for consistency in care and for specific chemotherapy training. Service delivery issues included the need for more clarity in the programme process, improved eligibility criteria, a focus on community laboratory coordination and development of centralised communications. PMID:19777723

  4. Proteomics Signature Profiling (PSP): A Novel Contextualization Approach for Cancer Proteomics

    PubMed Central

    2012-01-01

    Traditional proteomics analysis is plagued by the use of arbitrary thresholds resulting in large loss of information. We propose here a novel method in proteomics that utilizes all detected proteins. We demonstrate its efficacy in a proteomics screen of 5 and 7 liver cancer patients in the moderate and late stage, respectively. Utilizing biological complexes as a cluster vector, and augmenting it with submodules obtained from partitioning an integrated and cleaned protein–protein interaction network, we calculate a Proteomics Signature Profile (PSP) for each patient based on the hit rates of their reported proteins, in the absence of fold change thresholds, against the cluster vector. Using this, we demonstrated that moderate- and late-stage patients segregate with high confidence. We also discovered a moderate-stage patient who displayed a proteomics profile similar to other poor-stage patients. We identified significant clusters using a modified version of the SNet approach. Comparing our results against the Proteomics Expansion Pipeline (PEP) on which the same patient data was analyzed, we found good correlation. Building on this finding, we report significantly more clusters (176 clusters here compared to 70 in PEP), demonstrating the sensitivity of this approach. Gene Ontology (GO) terms analysis also reveals that the significant clusters are functionally congruent with the liver cancer phenotype. PSP is a powerful and sensitive method for analyzing proteomics profiles even when sample sizes are small. It does not rely on the ratio scores but, rather, whether a protein is detected or not. Although consistency of individual proteins between patients is low, we found the reported proteins tend to hit clusters in a meaningful and informative manner. By extracting this information in the form of a Proteomics Signature Profile, we confirm that this information is conserved and can be used for (1) clustering of patient samples, (2) identification of significant

  5. Neighborhood Rough Set Reduction-Based Gene Selection and Prioritization for Gene Expression Profile Analysis and Molecular Cancer Classification

    PubMed Central

    Hou, Mei-Ling; Wang, Shu-Lin; Li, Xue-Ling; Lei, Ying-Ke

    2010-01-01

    Selection of reliable cancer biomarkers is crucial for gene expression profile-based precise diagnosis of cancer type and successful treatment. However, current studies are confronted with overfitting and dimensionality curse in tumor classification and false positives in the identification of cancer biomarkers. Here, we developed a novel gene-ranking method based on neighborhood rough set reduction for molecular cancer classification based on gene expression profile. Comparison with other methods such as PAM, ClaNC, Kruskal-Wallis rank sum test, and Relief-F, our method shows that only few top-ranked genes could achieve higher tumor classification accuracy. Moreover, although the selected genes are not typical of known oncogenes, they are found to play a crucial role in the occurrence of tumor through searching the scientific literature and analyzing protein interaction partners, which may be used as candidate cancer biomarkers. PMID:20625410

  6. 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

  7. 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…

  8. Distinct health behavior and psychosocial profiles of young adult survivors of childhood cancers: a mixed methods study

    PubMed Central

    Lowe, Kincaid; Escoffery, Cam; Mertens, Ann C.; Berg, Carla J.

    2016-01-01

    Background We used a mixed-methods approach to examine health behavior profiles of young adult cancer survivors and characterize related sociodemographic and psychosocial factors. Methods We conducted a mail-based survey assessing sociodemographics, cancer treatment, health behaviors (e.g., tobacco use, physical activity), healthcare provider interactions, and psychosocial factors (e.g., Profile of Moods States [POMS]) among 106 young adult survivors from a southeastern cancer center and semi-structured interviews among a subset of 26. Results A k-means cluster analysis using eight health behaviors yielded three distinct health behavior profiles: high risk (n = 25), moderate risk (n = 39), and low risk (n = 40). High risks had the highest current alcohol, tobacco, and marijuana use; physical activity; and number of sexual partners (p’s < 0.001). They had higher symptoms of POMS tension-anxiety, depression-dejection, fatigue-inertia, and confusion-bewilderment (p’s < 0.05). Moderate risks had lowest physical activity (p < 0.05) but otherwise had moderate health behaviors. Low risks had the lowest alcohol, tobacco, and marijuana use and fewest sexual partners (p’s < 0.05). They had the lowest levels of tension-anxiety, depression-dejection, fatigue-inertia, and confusion-bewilderment (p’s < 0.05). Qualitative interviews showed that cancer had a range of effects on health behaviors and variable experiences regarding how healthcare providers address these behaviors. Conclusions Assessing health behavior profiles, rather than individual health behaviors, is informative in characterizing young adult cancer survivors and targeting survivorship care. Implications for Cancer Survivors Young adult cancer survivors demonstrate distinct health behavior profiles and are differentially impacted by the experience of cancer. Healthcare providers should be consistently intervening to ensure that survivors understand their specific health risks. PMID:26688575

  9. Microparticle conferred microRNA profiles - implications in the transfer and dominance of cancer traits

    PubMed Central

    2012-01-01

    Background Microparticles (MPs) are membrane vesicles which are released from normal and malignant cells following a process of budding and detachment from donor cells. MPs contain surface antigens, proteins and genetic material and serve as vectors of intercellular communication. MPs comprise the major source of systemic RNA including microRNA (miRNA), the aberrant expression of which appears to be associated with stage, progression and spread of many cancers. Our previous study showed that MPs carry both transcripts and miRNAs associated with the acquisition of multidrug resistance in cancer. Results Herein, we expand on our previous finding and demonstrate that MPs carry the transcripts of the membrane vesiculation machinery (floppase and scramblase) as well as nucleic acids encoding the enzymes essential for microRNA biogenesis (Drosha, Dicer and Argonaute). We also demonstrate using microarray miRNA profiling analysis, the selective packaging of miRNAs (miR-1228*, miR-1246, miR-1308, miR-149*, miR-455-3p, miR-638 and miR-923) within the MP cargo upon release from the donor cells. Conclusions These miRNAs are present in both haematological and non-haematological cancer cells and are involved in pathways implicated in cancer pathogenesis, membrane vesiculation and cascades regulated by ABC transporters. Our recent findings reinforce our earlier reports that MP transfer ‘re-templates’ recipient cells so as to reflect donor cell traits. We now demonstrate that this process is likely to occur via a process of selective packaging of nucleic acid species, including regulatory nucleic acids upon MP vesiculation. These findings have significant implications in understanding the cellular basis governing the intercellular acquisition and dominance of deleterious traits in cancers. PMID:22682234

  10. Cancer of the Uterus (Endometrial Cancer)

    MedlinePlus

    ... Management Education & Events Advocacy For Patients About ACOG Cancer of the Uterus [Endometrial Cancer] Home For Patients Search FAQs Cancer of the ... Uterus [Endometrial Cancer] FAQ097, May 2011 PDF Format Cancer of the Uterus [Endometrial Cancer] Gynecologic Problems What ...

  11. Proteomics profiling of cholangiocarcinoma exosomes: A potential role of oncogenic protein transferring in cancer progression.

    PubMed

    Dutta, Suman; Reamtong, Onrapak; Panvongsa, Wittaya; Kitdumrongthum, Sarunya; Janpipatkul, Keatdamrong; Sangvanich, Polkit; Piyachaturawat, Pawinee; Chairoungdua, Arthit

    2015-09-01

    Cholangiocarcinoma (CCA), a common primary malignant tumor of bile duct epithelia, is highly prevalent in Asian countries and unresponsive to chemotherapeutic drugs. Thus, a newly recognized biological entity for early diagnosis and treatment is highly needed. Exosomes are small membrane bound vesicles found in body fluids and released by most cell types including cancer cells. The vesicles contain specific subset of proteins and nucleic acids corresponding to cell types and play essential roles in pathophysiological processes. The present study aimed to assess the protein profiles of CCA-derived exosomes and their potential roles. We have isolated exosomes from CCA cells namely KKU-M213 and KKU-100 derived from Thai patients and their roles were investigated by incubation with normal human cholangiocyte (H69) cells. Exosomes were internalized into H69 cells and had no effects on viability or proliferation of the host cells. Interestingly, the exosomes from KKU-M213 cells only induced migration and invasion of H69 cells. Proteomic analysis of the exosomes from KKU-M213 cells disclosed multiple cancer related proteins that are not present in H69 exosomes. Consistent with the protein profile, treatment with KKU-M213 exosomes induced β-catenin and reduced E-cadherin expressions in H69 cells. Collectively, our results suggest that a direct cell-to-cell transfer of oncogenic proteins via exosomal pathway may be a novel mechanism for CCA progression and metastasis. PMID:26148937

  12. Changes in tumor-antigen expression profile as human small-cell lung cancers progress

    PubMed Central

    Ge, Li-Sheng; Hoa, Neil T.; Lambrecht, Nils; Dacosta-Iyer, Maria; Ouyang, Yi; Abolhoda, Amir; Jadus, Martin R.

    2015-01-01

    Objective Our group has previously observed that in patients with small-cell lung cancers (SCLCs), the expression of a tumor antigen, glioma big potassium (gBK) ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein (TAPP). We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production. Methods SCLC samples (eight surgical resections and three autopsy samples) and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets. Results Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of P53-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody. Conclusion Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages. PMID:26175925

  13. 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.

  14. Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis.

    PubMed

    Komatsu, Masato; Yoshimaru, Tetsuro; Matsuo, Taisuke; Kiyotani, Kazuma; Miyoshi, Yasuo; Tanahashi, Toshihito; Rokutan, Kazuhito; Yamaguchi, Rui; Saito, Ayumu; Imoto, Seiya; Miyano, Satoru; Nakamura, Yusuke; Sasa, Mitsunori; Shimada, Mitsuo; Katagiri, Toyomasa

    2013-02-01

    Triple negative breast cancer (TNBC) has a poor outcome due to the lack of beneficial therapeutic targets. To clarify the molecular mechanisms involved in the carcinogenesis of TNBC and to identify target molecules for novel anticancer drugs, we analyzed the gene expression profiles of 30 TNBCs as well as 13 normal epithelial ductal cells that were purified by laser-microbeam microdissection. We identified 301 and 321 transcripts that were significantly upregulated and downregulated in TNBC, respectively. In particular, gene expression profile analyses of normal human vital organs allowed us to identify 104 cancer-specific genes, including those involved in breast carcinogenesis such as NEK2, PBK and MELK. Moreover, gene annotation enrichment analysis revealed prominent gene subsets involved in the cell cycle, especially mitosis. Therefore, we focused on cell cycle regulators, asp (abnormal spindle) homolog, microcephaly-associated (Drosophila) (ASPM) and centromere protein K (CENPK) as novel therapeutic targets for TNBC. Small-interfering RNA-mediated knockdown of their expression significantly attenuated TNBC cell viability due to G1 and G2/M cell cycle arrest. Our data will provide a better understanding of the carcinogenesis of TNBC and could contribute to the development of molecular targets as a treatment for TNBC patients. PMID:23254957

  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. PMID:26656160

  16. Gene Expression Profiling of Evening Fatigue in Women Undergoing Chemotherapy for Breast Cancer.

    PubMed

    Kober, Kord M; Dunn, Laura; Mastick, Judy; Cooper, Bruce; Langford, Dale; Melisko, Michelle; Venook, Alan; Chen, Lee-May; Wright, Fay; Hammer, Marilyn; Schmidt, Brian L; Levine, Jon; Miaskowski, Christine; Aouizerat, Bradley E

    2016-07-01

    Moderate-to-severe fatigue occurs in up to 94% of oncology patients undergoing active treatment. Current interventions for fatigue are not efficacious. A major impediment to the development of effective treatments is a lack of understanding of the fundamental mechanisms underlying fatigue. In the current study, differences in phenotypic characteristics and gene expression profiles were evaluated in a sample of breast cancer patients undergoing chemotherapy (CTX) who reported low (n = 19) and high (n = 25) levels of evening fatigue. Compared to the low group, patients in the high evening fatigue group reported lower functional status scores, higher comorbidity scores, and fewer prior cancer treatments. One gene was identified as upregulated and 11 as downregulated in the high evening fatigue group. Gene set analysis found 24 downregulated and 94 simultaneously up- and downregulated pathways between the two fatigue groups. Transcript origin analysis found that differential expression (DE) originated primarily from monocytes and dendritic cell types. Query of public data sources found 18 gene expression experiments with similar DE profiles. Our analyses revealed that inflammation, neurotransmitter regulation, and energy metabolism are likely mechanisms associated with evening fatigue severity; that CTX may contribute to fatigue seen in oncology patients; and that the patterns of gene expression may be shared with other models of fatigue (e.g., physical exercise and pathogen-induced sickness behavior). These results suggest that the mechanisms that underlie fatigue in oncology patients are multifactorial. PMID:26957308

  17. 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. PMID:25291184

  18. Gene expression profiling of cancer stem cell in human lung adenocarcinoma A549 cells

    PubMed Central

    Seo, Dong-Cheol; Sung, Ji-Min; Cho, Hee-Jung; Yi, Hee; Seo, Kun-Ho; Choi, In-Soo; Kim, Dong-Ku; Kim, Jin-Suk; El-Aty AM, Abd; Shin, Ho-Chul

    2007-01-01

    Background The studies on cancer-stem-cells (CSCs) have attracted so much attention in recent years as possible therapeutic implications. This study was carried out to investigate the gene expression profile of CSCs in human lung adenocarcinoma A549 cells. Results We isolated CSCs from A549 cell line of which side population (SP) phenotype revealed several stem cell properties. After staining the cell line with Hoechst 33342 dye, the SP and non-side population (non-SP) cells were sorted using flow cytometric analysis. The mRNA expression profiles were measured using an Affymetrix GeneChip® oligonucleotide array. Among the sixty one differentially expressed genes, the twelve genes inclusive three poor prognostic genes; Aldo-keto reductase family 1, member C1/C2 (AKR1C1/C2), Transmembrane 4 L six family member 1 nuclear receptor (TM4SF1), and Nuclear receptor subfamily 0, group B, member 1 (NR0B1) were significantly up-regulated in SP compared to non-SP cells. Conclusion This is the first report indicating the differences of gene expression pattern between SP and non-SP cells in A549 cells. We suggest that the up-regulations of the genes AKR1C1/C2, TM4SF1 and NR0B1 in SP of human adenocarcinoma A549 cells could be a target of poor prognosis in anti-cancer therapy. PMID:18034892

  19. 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 ...

  20. 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)

  1. 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…

  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. PMID:27035224

  3. Molecular Profiling in Unknown Primary Cancer: Accuracy of Tissue of Origin Prediction

    PubMed Central

    Spigel, David R.; Yardley, Denise A.; Erlander, Mark G.; Ma, Xiao-Jun; Hainsworth, John D.

    2010-01-01

    Introduction. This retrospective, multi-institutional study evaluated the accuracy of tissue-of-origin prediction by molecular profiling in patients with carcinoma of unknown primary site (CUP). Methods. Thirty-eight of 501 patients (7.6%) with CUP, seen in 2000–2008, had their latent primary site tumor subsequently identified during life. Twenty-eight of these patients (73.7%) had adequate initial tissue biopsies available for molecular profiling with a reverse transcriptase-polymerase chain reaction (RT-PCR) assay (Cancer Type ID; bioTheranostics, Inc., San Diego, CA). The assay was performed on formalin-fixed paraffin-embedded biopsy specimens in a blinded fashion, and the assay results were compared with clinicopathologic data and the actual latent primary sites. Results. Twenty of the 28 (71.4%) RT-PCR assays were successfully completed (eight biopsies had either insufficient tumor or poorly preserved RNA). Fifteen of the 20 assay predictions (75%) were correct (95% confidence interval, 60%–85%), corresponding to the actual latent primary sites identified after the initial diagnosis of CUP. Primary sites correctly identified included breast (four patients), ovary/primary peritoneal (four patients), non-small cell lung (three patients), colorectal (two patients), gastric (one patient), and melanoma (one patient). Three predictions were incorrect (intestinal, testicular, sarcoma) in patients with gastroesophageal, pancreatic, and non-small cell lung cancer, respectively, and two were unclassifiable in patients with non-small cell lung cancer. Clinicopathologic findings were helpful in suggesting the correct primary site in some patients and appear to complement the molecular assay findings. Conclusions. These data validate the reliability of this assay in predicting the primary site in CUP patients and may form the basis for more successful site-directed therapy, when used in concert with clinicopathologic data. PMID:20427384

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

    PubMed Central

    LONG, JIN; LIU, ZHE; WU, XINGDA; XU, YUANHONG; GE, CHUNLIN

    2016-01-01

    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. PMID:27035224

  5. Identification of Intrinsic Imaging Phenotypes for Breast Cancer Tumors: Preliminary Associations with Gene Expression Profiles1

    PubMed Central

    Ashraf, Ahmed Bilal; Daye, Dania; Gavenonis, Sara; Mies, Carolyn; Feldman, Michael; Rosen, Mark; Kontos, Despina

    2015-01-01

    Purpose To present a method for identifying intrinsic imaging phenotypes in breast cancer tumors and to investigate their association with prognostic gene expression profiles. Materials and Methods The authors retrospectively analyzed dynamic contrast material–enhanced (DCE) magnetic resonance (MR) images of the breast in 56 women (mean age, 55.6 years; age range, 37–74 years) diagnosed with estrogen receptor–positive breast cancer between 2005 and 2010. The study was approved by the institutional review board and compliant with HIPAA. The requirement to obtain informed consent was waived. Primary tumors were assayed with a validated gene expression assay that provides a score for the likelihood of recurrence. A multiparametric imaging phenotype vector was extracted for each tumor by using quantitative morphologic, kinetic, and spatial heterogeneity features. Multivariate linear regression was performed to test associations between DCE MR imaging features and recurrence likelihood. To identify intrinsic imaging phenotypes, hierarchical clustering was performed on the extracted feature vectors. Multivariate logistic regression was used to classify tumors at high versus low or medium risk of recurrence. To determine the additional value of intrinsic phenotypes, the phenotype category was tested as an additional variable. Receiver operating characteristic analysis and the area under the receiver operating characteristic curve (Az) were used to assess classification performance. Results There was a moderate correlation (r = 0.71, R2 = 0.50, P < .001) between DCE MR imaging features and the recurrence score. DCE MR imaging features were predictive of recurrence risk as determined by the surrogate assay, with an Az of 0.77 (P < .01). Four dominant imaging phenotypes were detected, with two including only low- and medium-risk tumors. When the phenotype category was used as an additional variable, the Az increased to 0.82 (P < .01). Conclusion Intrinsic imaging

  6. Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process

    PubMed Central

    Chandran, Uma R; Ma, Changqing; Dhir, Rajiv; Bisceglia, Michelle; Lyons-Weiler, Maureen; Liang, Wenjing; Michalopoulos, George; Becich, Michael; Monzon, Federico A

    2007-01-01

    Background Prostate cancer is characterized by heterogeneity in the clinical course that often does not correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. Methods Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. Results The metastatic samples are highly heterogenous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodelling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). Conclusion We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer. PMID:17430594

  7. Gene Expression Profiling of Liver Cancer Stem Cells by RNA-Sequencing

    PubMed Central

    Lam, Chi Tat; Ng, Michael N. P.; Yu, Wan Ching; Lau, Joyce; Wan, Timothy; Wang, Xiaoqi; Yan, Zhixiang; Liu, Hang; Fan, Sheung Tat

    2012-01-01

    Background Accumulating evidence supports that tumor growth and cancer relapse are driven by cancer stem cells. Our previous work has demonstrated the existence of CD90+ liver cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). Nevertheless, the characteristics of these cells are still poorly understood. In this study, we employed a more sensitive RNA-sequencing (RNA-Seq) to compare the gene expression profiling of CD90+ cells sorted from tumor (CD90+CSCs) with parallel non-tumorous liver tissues (CD90+NTSCs) and elucidate the roles of putative target genes in hepatocarcinogenesis. Methodology/Principal Findings CD90+ cells were sorted respectively from tumor and adjacent non-tumorous human liver tissues using fluorescence-activated cell sorting. The amplified RNAs of CD90+ cells from 3 HCC patients were subjected to RNA-Seq analysis. A differential gene expression profile was established between CD90+CSCs and CD90+NTSCs, and validated by quantitative real-time PCR (qRT-PCR) on the same set of amplified RNAs, and further confirmed in an independent cohort of 12 HCC patients. Five hundred genes were differentially expressed (119 up-regulated and 381 down-regulated genes) between CD90+CSCs and CD90+NTSCs. Gene ontology analysis indicated that the over-expressed genes in CD90+CSCs were associated with inflammation, drug resistance and lipid metabolism. Among the differentially expressed genes, glypican-3 (GPC3), a member of glypican family, was markedly elevated in CD90+CSCs compared to CD90+NTSCs. Immunohistochemistry demonstrated that GPC3 was highly expressed in forty-two human liver tumor tissues but absent in adjacent non-tumorous liver tissues. Flow cytometry indicated that GPC3 was highly expressed in liver CD90+CSCs and mature cancer cells in liver cancer cell lines and human liver tumor tissues. Furthermore, GPC3 expression was positively correlated with the number of CD90+CSCs in liver tumor tissues. Conclusions/Significance The identified genes

  8. Antibody microarray profiling of human prostate cancer sera: antibody screening and identification of potential biomarkers.

    PubMed

    Miller, Jeremy C; Zhou, Heping; Kwekel, Joshua; Cavallo, Robert; Burke, Jocelyn; Butler, E Brian; Teh, Bin S; Haab, Brian B

    2003-01-01

    We developed a practical strategy for serum protein profiling using antibody microarrays and applied the method to the identification of potential biomarkers in prostate cancer serum. Protein abundances from 33 prostate cancer and 20 control serum samples were compared to abundances from a common reference pool using a two-color fluorescence assay. Robotically spotted microarrays containing 184 unique antibodies were prepared on two different substrates: polyacrylamide based hydrogels on glass and poly-1-lysine coated glass with a photoreactive cross-linking layer. The hydrogel substrate yielded an average six-fold higher signal-to-noise ratio than the other substrate, and detection of protein binding was possible from a greater number of antibodies using the hydrogels. A statistical filter based on the correlation of data from "reverse-labeled" experiment sets accurately predicted the agreement between the microarray measurements and enzyme-linked immunosorbent assay measurements, showing that this parameter can serve to screen for antibodies that are functional on microarrays. Having defined a set of reliable microarray measurements, we identified five proteins (von Willebrand Factor, immunoglobulinM, Alpha1-antichymotrypsin, Villin and immunoglobulinG) that had significantly different levels between the prostate cancer samples and the controls. These developments enable the immediate use of high-density antibody and protein microarrays in biomarker discovery studies. PMID:12548634

  9. Clinical profile and epidemiological factors of oral cancer patients from North India

    PubMed Central

    Singh, Mahendra Pratap; Misra, Sanjeev; Rathanaswamy, Siva Prakash; Gupta, Sameer; Tewari, Brij Nath; Bhatt, Madan Lal Brahma; Kumar, Vijay

    2015-01-01

    Introduction: Tobacco chewing, smoking, and alcohol consumption are major contributing factors in the development of oral carcinoma. India has world's highest number of oral cancers (almost 20%) and approximately 1% of the Indian population has oral premalignant lesions. Aim: The purpose of the study was to evaluate the epidemiological factors and clinical profile of oral cancer cases in our hospital. Settings: Department of Surgical Oncology, King George's Medical University, Lucknow, India. Materials and Methods: A retrospective study was conducted from January 2010 to December 2012 on 479 cases with histopathologically confirmed oral carcinoma. Subjects’ details of age, sex, occupation, tobacco consumption, site of carcinoma, and stage at presentation were recorded. Results: Mean age in this study was 47.84 years with male to female ratio of 3.1:1.0. Buccal mucosa and alveolus were the most affected sites. The majority of cases were from socially and economically weaker section, with 93.72% cases being tobacco users. The majority of cases were advance stage (Stage III and IV) with Stage IV being the predominant stage at presentation followed by Stage III. Conclusion: The findings of the study reveal that tobacco consumption is one of the major contributors in the development of cancer of oral cavity with the majority of cases presenting in advance stages posing a big therapeutic challenge. PMID:26668448

  10. 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. PMID:24804215

  11. Extracellular Matrix Proteins Expression Profiling in Chemoresistant Variants of the A2780 Ovarian Cancer Cell Line

    PubMed Central

    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. PMID:24804215

  12. 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. PMID:18310284

  13. Molecular Profiling of the ‘Plexinome’ in melanoma and pancreatic cancer

    PubMed Central

    Balakrishnan, Asha; Penachioni, Junia Y.; Lamba, Simona; Bleeker, Fonnet E; Zanon, Carlo; Rodolfo, Monica; Vallacchi, Viviana; Scarpa, Aldo; Felicioni, Lara; Buck, Matthias; Marchetti, Antonio; Comoglio, Paolo M.; Bardelli, Alberto; Tamagnone, Luca

    2010-01-01

    Plexins are transmembrane high-affinity receptors for semaphorins, regulating cell guidance, motility and invasion. Functional evidences implicate semaphorin signals in cancer progression and metastasis. Yet, it is largely unknown whether plexin genes are genetically altered in human tumors. We performed a comprehensive gene copy analysis and mutational profiling of all nine members of the plexin gene family (plexinome), in melanomas and pancreatic ductal adenocarcinomas (PDACs), which are characterized by high metastatic potential and poor prognosis. Gene copy analysis detected amplification of PLXNA4 in melanomas, while copy number losses of multiple plexin genes were seen in PDACs. Somatic mutations were detected in PLXNA4, PLXNB3 and PLXNC1; providing the first evidence that these plexins are mutated in human cancer. Functional assays in cellular models revealed that some of these missense mutations result in loss of plexin function. For instance, c.1613G>A, p.R538H mutation in the extracellular domain of PLXNB3 prevented binding of the ligand Sema5A. Moreover, while PLXNA4 signaling can inhibit tumor cell migration, the mutated c.5206C>T, p.H1736Y allele had lost this activity. Our study is the first systematic analysis of the “plexinome” in human tumors, and indicates that multiple mutated plexins may be involved in cancer progression. PMID:19462467

  14. 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

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

    PubMed Central

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

    2013-01-01

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

  16. Nab-Paclitaxel in Metastatic Breast Cancer: Defining the Best Patient Profile.

    PubMed

    González-Martín, Antonio; Alba, Emilio; Ciruelos, Eva; Cortés, Javier; Llombart, Antonio; Lluch, Ana; Andrés, Raquel; Álvarez, Isabel; Aramendía, José Manuel; de la Peña, Francisco Ayala; Barnadas, Agustí; Batista, Norberto; Calvo, Lourdes; Galve, Elena; García-Palomo, Andrés; García-Sáenz, José Ángel; de la Haba, Juan; López, Rafael; López-Vivanco, Guillermo; Martínez-Jáñez, Noelia; de Dueñas, Eduardo Martínez; Plazaola, Arrate; Rodríguez-Lescure, Álvaro; Ruiz, Manuel; Sánchez-Rovira, Pedro; Santaballa, Ana; Seguí, Miguel Ángel; Tusquets, Ignasi; Zamora, Pilar; Martín, Miguel

    2016-01-01

    Around 40% of patients with breast cancer will present with a recurrence of the disease. Chemotherapy is recommended for patients with recurrent hormone-independent or hormone-refractory breast cancer and almost all patients with metastatic breast cancer (MBC) receive chemotherapy during their medical history. Nanoparticle albuminbound (nab)-paclitaxel is a solvent-free, 130-nanometer particle formulation of paclitaxel. Nab-paclitaxel can be administered to all patients for whom the treatment choice is a taxane. In this review, 6 patient profiles for which nabpaclitaxel may be particularly useful are described and analyzed: (i) as first-line treatment of MBC, (ii) as second-line treatment of MBC after oral chemotherapy, (iii) after a standard taxane, (iv) as third-line treatment after a standard taxane and oral chemotherapy, (v) for patients with HER2-positive MBC and (vi) for patients with intolerance to standard taxanes. Nab-paclitaxel is a rational treatment choice for patients with MBC in different settings, as well as for those with prior exposure to a standard taxane. PMID:26278712

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

    PubMed

    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

  18. 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.

  19. Novel drug candidates for the treatment of metastatic colorectal cancer through global inverse gene-expression profiling.

    PubMed

    van Noort, Vera; Schölch, Sebastian; Iskar, Murat; Zeller, Georg; Ostertag, Kristina; Schweitzer, Christine; Werner, Kristin; Weitz, Jürgen; Koch, Moritz; Bork, Peer

    2014-10-15

    Drug-induced gene-expression profiles that invert disease profiles have recently been illustrated to be a starting point for drug repositioning. In this study, we validate this approach and focus on prediction of novel drugs for colorectal cancer, for which there is a pressing need to find novel antimetastatic compounds. We computationally predicted three novel and still unknown compounds against colorectal cancer: citalopram (an antidepressant), troglitazone (an antidiabetic), and enilconazole (a fungicide). We verified the compounds by in vitro assays of clonogenic survival, proliferation, and migration and in a subcutaneous mouse model. We found evidence that the mode of action of these compounds may be through inhibition of TGFβ signaling. Furthermore, one compound, citalopram, reduced tumor size as well as the number of circulating tumor cells and metastases in an orthotopic mouse model of colorectal cancer. This study proposes citalopram as a potential therapeutic option for patients with colorectal cancer, illustrating the potential of systems pharmacology. PMID:25038229

  20. 6 Common Cancers - Lung Cancer

    MedlinePlus

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

  1. 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 ...

  2. 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 ...

  3. Predicting the home location of serial offenders: a preliminary comparison of the accuracy of human judges with a geographic profiling system.

    PubMed

    Snook, Brent; Canter, David; Bennell, Craig

    2002-01-01

    The accuracy with which human judges, before and after 'training', could predict the likely home location of serial offenders was compared with predictions produced by a geographic profiling system known as Dragnet. All predictions were derived from ten spatial displays, one for each of ten different U.S. serial murderers, indicating five crime locations. In all conditions participants were asked to place an 'X' on each spatial display corresponding to where they thought the offender lived. In the control condition, a comparison was made between the accuracy of these predictions for 21 participants on two separate occasions a few minutes apart. In the experimental condition, between their first and second predictions the 21 participants were given two heuristics to follow--distance-decay and circle hypothesis. Results showed that participants with no previous knowledge of geographic profiling were able to use the two heuristics to improve the accuracy of their predictions. The overall accuracy of the second set of predictions for the experimental group was also not significantly different from the accuracy of predictions generated by Dragnet. PMID:11979494

  4. 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

  5. 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.

  6. miRNA profiling of circulating EpCAM(+) extracellular vesicles: promising biomarkers of colorectal cancer.

    PubMed

    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

  7. Quality Control Usage in High-Density Microarrays Reveals Differential Gene Expression Profiles in Ovarian Cancer.

    PubMed

    Villegas-Ruiz, Vanessa; Moreno, Jose; Jacome-Lopez, Karina; Zentella-Dehesa, Alejandro; Juarez-Mendez, Sergio

    2016-01-01

    There are several existing reports of microarray chip use for assessment of altered gene expression in different diseases. In fact, there have been over 1.5 million assays of this kind performed over the last twenty years, which have influenced clinical and translational research studies. The most commonly used DNA microarray platforms are Affymetrix GeneChip and Quality Control Software along with their GeneChip Probe Arrays. These chips are created using several quality controls to confirm the success of each assay, but their actual impact on gene expression profiles had not been previously analyzed until the appearance of several bioinformatics tools for this purpose. We here performed a data mining analysis, in this case specifically focused on ovarian cancer, as well as healthy ovarian tissue and ovarian cell lines, in order to confirm quality control results and associated variation in gene expression profiles. The microarray data used in our research were downloaded from ArrayExpress and Gene Expression Omnibus (GEO) and analyzed with Expression Console Software using RMA, MAS5 and Plier algorithms. The gene expression profiles were obtained using Partek Genomics Suite v6.6 and data were visualized using principal component analysis, heat map, and Venn diagrams. Microarray quality control analysis showed that roughly 40% of the microarray files were false negative, demonstrating over- and under-estimation of expressed genes. Additionally, we confirmed the results performing second analysis using independent samples. About 70% of the significant expressed genes were correlated in both analyses. These results demonstrate the importance of appropriate microarray processing to obtain a reliable gene expression profile. PMID:27268623

  8. Integrated Genomic and Transcriptional Profiling Identifies Chromosomal Loci with Altered Gene Expression in Cervical Cancer

    PubMed Central

    Wilting, Saskia M.; de Wilde, Jillian; Meijer, Chris J. L. M.; Berkhof, Johannes; Yi, Yajun; van Wieringen, Wessel N.; Braakhuis, Boudewijn J. M.; Meijer, Gerrit A.; Ylstra, Bauke; Snijders, Peter J. F.; Steenbergen, Renske D. M.

    2009-01-01

    For a better understanding of the consequences of recurrent chromosomal alterations in cervical carcinomas, we integrated genome-wide chromosomal and transcriptional profiles of 10 squamous cell carcinomas (SCCs), 5 adenocarcinomas (AdCAs) and 6 normal controls. Previous genomic profiling showed that gains at chromosome arms 1q, 3q, and 20q as well as losses at 8q, 10q, 11q, and 13q were common in cervical carcinomas. Altered regions spanned multiple megabases, and the extent to which expression of genes located there is affected remains unclear. Expression analysis of these previously chromosomally profiled carcinomas yielded 83 genes with significantly differential expression between carcinomas and normal epithelium. Application of differential gene locus mapping (DIGMAP) analysis and the array CGH expression integration tool (ACE-it) identified hotspots within large chromosomal alterations in which gene expression was altered as well. Chromosomal gains of the long arms of chromosome 1, 3, and 20 resulted in increased expression of genes located at 1q32.1-32.2, 3q13.32-23, 3q26.32-27.3, and 20q11.21-13.33, whereas a chromosomal loss of 11q22.3-25 was related to decreased expression of genes located in this region. Overexpression of DTX3L, PIK3R4, ATP2C1, and SLC25A36, all located at 3q21.1-23 and identified by DIGMAP, ACE-it or both, was confirmed in an independent validation sample set consisting of 12 SCCs and 13 normal ectocervical samples. In conclusion, integrated chromosomal and transcriptional profiling identified chromosomal hotspots at 1q, 3q, 11q, and 20q with altered gene expression within large commonly altered chromosomal regions in cervical cancer. PMID:18618715

  9. Prospective Molecular Profiling of Canine Cancers Provides a Clinically Relevant Comparative Model for Evaluating Personalized Medicine (PMed) Trials

    PubMed Central

    Mazcko, Christina; Cherba, David; Hendricks, William; Lana, Susan; Ehrhart, E. J.; Charles, Brad; Fehling, Heather; Kumar, Leena; Vail, David; Henson, Michael; Childress, Michael; Kitchell, Barbara; Kingsley, Christopher; Kim, Seungchan; Neff, Mark; Davis, Barbara

    2014-01-01

    Background Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. Methodology A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Conclusions Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (<1 week). Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer

  10. Minimally invasive genomic and transcriptomic profiling of visceral cancers by next-generation sequencing of circulating exosomes

    PubMed Central

    San Lucas, F. A.; Allenson, K.; Bernard, V.; Castillo, J.; Kim, D. U.; Ellis, K.; Ehli, E. A.; Davies, G. E.; Petersen, J. L.; Li, D.; Wolff, R.; Katz, M.; Varadhachary, G.; Wistuba, I.; Maitra, A.; Alvarez, H.

    2016-01-01

    Background The ability to perform comprehensive profiling of cancers at high resolution is essential for precision medicine. Liquid biopsies using shed exosomes provide high-quality nucleic acids to obtain molecular characterization, which may be especially useful for visceral cancers that are not amenable to routine biopsies. Patients and methods We isolated shed exosomes in biofluids from three patients with pancreaticobiliary cancers (two pancreatic, one ampullary). We performed comprehensive profiling of exoDNA and exoRNA by whole genome, exome and transcriptome sequencing using the Illumina HiSeq 2500 sequencer. We assessed the feasibility of calling copy number events, detecting mutational signatures and identifying potentially actionable mutations in exoDNA sequencing data, as well as expressed point mutations and gene fusions in exoRNA sequencing data. Results Whole-exome sequencing resulted in 95%–99% of the target regions covered at a mean depth of 133–490×. Genome-wide copy number profiles, and high estimates of tumor fractions (ranging from 56% to 82%), suggest robust representation of the tumor DNA within the shed exosomal compartment. Multiple actionable mutations, including alterations in NOTCH1 and BRCA2, were found in patient exoDNA samples. Further, RNA sequencing of shed exosomes identified the presence of expressed fusion genes, representing an avenue for elucidation of tumor neoantigens. Conclusions We have demonstrated high-resolution profiling of the genomic and transcriptomic landscapes of visceral cancers. A wide range of cancer-derived biomarkers could be detected within the nucleic acid cargo of shed exosomes, including copy number profiles, point mutations, insertions, deletions, gene fusions and mutational signatures. Liquid biopsies using shed exosomes has the potential to be used as a clinical tool for cancer diagnosis, therapeutic stratification and treatment monitoring, precluding the need for direct tumor sampling. PMID

  11. Zoster in children with cancer: radioimmune precipitation profiles of sera before and after illness.

    PubMed

    Grose, C

    1983-01-01

    Sera collected from children with cancer before and for extended periods after the onset of zoster were analyzed by radioimmune precipitation techniques. The percent recovery of both [3H]fucose- and [35S]methionine-labeled varicella-zoster virus (VZV)-specific antigens increased severalfold immediately after zoster and declined slowly during convalescence; however, within two years serum panels from two patients exhibited serologic evidence of subclinical reactivation of VZV. After electrophoretic fractionation of the immunoprecipitates, the polypeptide profile after zoster closely resembled that described for high titer xenoantisera to VZV and contained at least 16 constituents ranging in molecular weight from 32 to 174,000. In contrast, sera obtained before zoster were easily distinguished because they precipitated poorly, if at all, two major VZV glycoproteins (gp62 and gp98) and several nonglycosylated polypeptides. The emergence of zoster, therefore, was associated with the appearance of previously undetectable antibodies to VZV-specific proteins. PMID:6296242

  12. Profiling of Multiple Targets of Artemisinin Activated by Hemin in Cancer Cell Proteome.

    PubMed

    Zhou, Yiqing; Li, Weichao; Xiao, Youli

    2016-04-15

    The antimalarial drug artemisinin is found to have diverse biological activities ranging from anti-inflammatory to anticancer properties; however, as of today, the cellular targets and mechanism of action of this important compound have remained elusive. Here, we report the global protein target profiling of artemisinin in the HeLa cancer cell proteome using a chemical proteomics approach. In the presence of hemin, multiple proteins were targeted by artemisinin probe through covalent modification. Further studies revealed that reducing of hemin to heme by protein thiols was essential for endoperoxide activation and subsequent protein alkylation. Artemisinin may exert its synergistic therapeutic anticancer effects via modulation of a variety of cellular pathways through acting on multiple targets. PMID:26854499

  13. Profile of ramucirumab in the treatment of metastatic non-small-cell lung cancer

    PubMed Central

    Cooper, Maryann R; Binkowski, Chelsea; Hartung, Jessica; Towle, Jennifer

    2016-01-01

    The interaction between vascular endothelial growth factor and its receptor is an important therapeutic target due to the importance of this pathway in carcinogenesis. In particular, this pathway promotes and regulates angiogenesis as well as increases endothelial cell proliferation, permeability, and survival. Ramucirumab is a fully human monoclonal antibody that specifically targets the vascular endothelial growth factor receptor-2, the key receptor implicated in angiogenesis. Currently, ramucirumab is approved for the second-line treatment of metastatic non-small-cell lung cancer (NSCLC) in combination with docetaxel. In a Phase III clinical trial, ramucirumab was shown to improve the overall survival in patients with disease progression, despite platinum-based chemotherapy for advanced NSCLC. This review describes the pharmacology, pharmacokinetics and dynamics, adverse event profile, and the clinical activity of ramucirumab observed in Phase II and III trials in NSCLC. PMID:27110124

  14. Age differences in the last week of life in advanced cancer patients followed at home.

    PubMed

    Mercadante, Sebastiano; Aielli, Federica; Masedu, Francesco; Valenti, Marco; Verna, Lucilla; Porzio, Giampiero

    2016-04-01

    A retrospective analysis of a consecutive sample of patients admitted to a home care program was performed. Data were recorded in the last week through a backward analysis from the day before death as follows: 1 week before dying (-1W), 3 days before death (-3D), and the day before dying (-1D). Data to be collected included the Edmonton Symptom Assessment System (ESAS), background pain intensity, the prevalence of breakthrough pain, the use of opioids in the last week, and the need for palliative sedation, with indications, duration, and drugs used. Patients were distributed according to the following age ranges: adults (<65 years, A) and aged (≥65 years, O). Of the latter group, three subgroups were assessed: old (65-74 years, O1), very old (75-84 years, O2), and the oldest (≥85 years, O3). Four hundred eleven patients were assessed. At -W1, no statistical differences in intensity of ESAS items ≥4 among the age subgroups were found. For ESAS values at -1W, -3D, and -1D, no statistical differences were found unless for anorexia at -1W (p = 0.000) (more likely), depression at -3D (p = 0.000) (less likely), depression (p = 0.000), and dyspnea (p = 0.01) (less likely) at -1D in the oldest group (O3). No differences in pain intensity among the groups were found (p = 0.54). Opioid doses increased in time and were significantly lower in older patients (p = 0.000). The subcutaneous route was more frequently used at -3D and -1D in older patients. No differences in opioid switching were found among the groups (p = 0.56). Adult patients required more often palliative sedation (p = 0.003). Older patients have problems relatively similar to adult patients in the last week of life, unless for some symptoms. Older patients had also a lower opioid consumption, a more frequent use of the subcutaneous route, and a lower need for palliative sedation. PMID:26471279

  15. 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

  16. Targeted serum metabolite profiling and sequential metabolite ratio analysis for colorectal cancer progression monitoring.

    PubMed

    Zhu, Jiangjiang; Djukovic, Danijel; Deng, Lingli; Gu, Haiwei; Himmati, Farhan; Abu Zaid, Mohammad; Chiorean, Elena Gabriela; Raftery, Daniel

    2015-10-01

    Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and a major cause of human morbidity and mortality. In addition to early detection, close monitoring of disease progression in CRC can be critical for patient prognosis and treatment decisions. Efforts have been made to develop new methods for improved early detection and patient monitoring; however, research focused on CRC surveillance for treatment response and disease recurrence using metabolomics has yet to be reported. In this proof of concept study, we applied a targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) metabolic profiling approach focused on sequential metabolite ratio analysis of serial serum samples to monitor disease progression from 20 CRC patients. The use of serial samples reduces patient to patient metabolic variability. A partial least squares-discriminant analysis (PLS-DA) model using a panel of five metabolites (succinate, N2, N2-dimethylguanosine, adenine, citraconic acid, and 1-methylguanosine) was established, and excellent model performance (sensitivity = 0.83, specificity = 0.94, area under the receiver operator characteristic curve (AUROC) = 0.91 was obtained, which is superior to the traditional CRC monitoring marker carcinoembryonic antigen (sensitivity = 0.75, specificity = 0.76, AUROC = 0.80). Monte Carlo cross validation was applied, and the robustness of our model was clearly observed by the separation of true classification models from the random permutation models. Our results suggest the potential utility of metabolic profiling for CRC disease monitoring. PMID:26342311

  17. Post-translational modification profiling - A novel tool for mapping the protein modification landscape in cancer.

    PubMed

    Eisenberg-Lerner, Avital; Ciechanover, Aaron; Merbl, Yifat

    2016-08-01

    The ubiquitin system plays an important role in essentially every cellular process, regulating numerous pathways ranging from development, transcription, DNA damage response, cell cycle, and signal transduction. Its best studied role involves removal of faulty proteins or those that are not necessary anymore. Aberrations in the ubiquitin system have been implicated in various pathologies including cancer, where specific mutations in E3 ligases such as Mdm2, pVHL, and BRCA1 have been linked to disease progression, prognosis, and resistance to drugs. Yet, there are hundreds of E3 ligases in the human genome and our knowledge of their target proteins and their dynamic regulation in the cellular environment is largely limited. In addition, fundamental questions related to recognition and specificity in ubiquitin conjugation remain unanswered. It is thus of major importance to characterize the ubiquitin landscape under various cellular conditions, and study how the regulatory network is altered in health and disease. To do so, analytical tools that allow identification of ubiquitin substrates, the conjugation and removal of ubiquitin, and the nature of specific ubiquitin linkages that are formed are needed. In this mini-review, we discuss common proteomic methodologies applied to studying the ubiquitome, and specifically focus on our recently developed post-translational modification (PTM) profiling approach. PTM profiling is a functional assay, amenable to biochemical manipulation, which allows the detection of protein modifications in a high-throughput manner. We discuss in detail the advantages and limitations of this system, focusing primarily on examples for analyzing the ubiquitin system in cancer. Uncovering the intricate signaling dynamics governed by and regulating ubiquitin modifications should clearly evolve into a new paradigm in understanding the molecular basis of malignant transformation and the development of novel therapeutic modalities. PMID:27229346

  18. Expression profiling and long lasting responses to chemotherapy in metastatic gastric cancer.

    PubMed

    Lo Nigro, Cristiana; Monteverde, Martino; Riba, Michela; Lattanzio, Laura; Tonissi, Federica; Garrone, Ornella; Heouaine, Abdelhamid; Gallo, Fabio; Ceppi, Marcello; Borghi, Felice; Comino, Alberto; Merlano, Marco

    2010-11-01

    Current palliative chemotherapy (CT) regimens achieve clinical benefits in less than 50% of patients treated for metastatic gastric cancers, and long-term survivals are anecdotical. Genetic polymorphisms and differences at the level of transcription in genes involved in biological processes of drug metabolism, DNA repair and drug resistance can explain the observed individual differences in response to drugs, in survival and in different susceptibility to the toxic effects of CT. The possibility to classify patients on the basis of genetic signatures could help in choosing the CT regimen. We present herein an analysis of genetic and expression profiling of three patients affected by metastatic gastric cancer, treated with CT and alive, disease-free, at 66-82 months. Four patients with typical clinical outcome represented the control group. Expression profiling from paraffin-embedded tumor tissues was performed on an ad hoc set of genes involved in drug metabolism and resistance, DNA repair, cell cycle regulation and growth factors signalling. Genetic polymorphism analysis on DNA extracted from peripheral blood was done by pyrosequencing of genetic markers predictive of drug response. Expression analysis in long-term survivors revealed a significant upregulation of PTEN, TP63, GADD45a and MAPK1 genes. We found also an upregulation of CYP1A1, CYP3A4 and ERBB4 genes. EGF was found to be down-regulated in long-term survivors. ERCC1 C8092A polymorphism seems to be associated with survival in our set of patients. The present study shed light on a set of genes, which could have a predictive role in survival of patients with metastatic gastric tumors. PMID:20878069

  19. Microarray-based transcriptional and epigenetic profiling of matrix metalloproteinases, collagens, and related genes in cancer.

    PubMed

    Chernov, Andrei V; Baranovskaya, Svetlana; Golubkov, Vladislav S; Wakeman, Dustin R; Snyder, Evan Y; Williams, Roy; Strongin, Alex Y

    2010-06-18

    Epigenetic parameters (DNA methylation, histone modifications, and miRNAs) play a significant role in cancer. To identify the common epigenetic signatures of both the individual matrix metalloproteinases (MMPs) and the additional genes, the function of which is also linked to proteolysis, migration, and tumorigenesis, we performed epigenetic profiling of 486 selected genes in unrelated non-migratory MCF-7 breast carcinoma and highly migratory U251 glioma cells. Genome-wide transcriptional profiling, quantitative reverse transcription-PCR, and microRNA analyses were used to support the results of our epigenetic studies. Transcriptional silencing in both glioma and breast carcinoma cells predominantly involved the repressive histone H3 Lys-27 trimethylation (H3K27me3) mark. In turn, epigenetic stimulation was primarily performed through a gain in the histone H3 Lys-4 dimethylation (H3K4me2) and H3 hyperacetylation and by a global reduction of H3K27me3. Inactive pro-invasive genes in MCF-7 cells but not in U251 cells frequently exhibited a stem cell-like bivalent mark (enrichment in both H3K27me3 and H3K4me2), a characteristic of developmental genes. In contrast with other MMPs, MMP-8 was epigenetically silenced in both cell types, thus providing evidence for the strict epigenetic control of this anti-tumorigenic proteinase in cancer. Epigenetic stimulation of multiple collagen genes observed in cultured glioma cells was then directly confirmed using orthotopic xenografts and tumor specimens. We suggest that the epigenetic mechanisms allow gliomas to deposit an invasion-promoting collagen-enriched matrix and then to use this matrix to accomplish their rapid migration through the brain tissue. PMID:20404328

  20. 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.

  1. Gene profiling and circulating tumor cells as biomarker to prognostic of patients with locoregional breast cancer.

    PubMed

    Kuniyoshi, Renata K; Gehrke, Flávia de Sousa; Alves, Beatriz C A; Vilas-Bôas, Viviane; Coló, Anna E; Sousa, Naiara; Nunes, João; Fonseca, Fernando L A; Del Giglio, Auro

    2015-09-01

    The gene profile of primary tumors, as well as the identification of circulating tumor cells (CTCs), can provide important prognostic and predictive information. In this study, our objective was to perform tumor gene profiling (TGP) in combination with CTC characterization in women with nonmetastatic breast cancer. Biological samples (from peripheral blood and tumors) from 167 patients diagnosed with stage I, II, and III mammary carcinoma, who were also referred for adjuvant/neoadjuvant chemotherapy, were assessed for the following parameters: (a) the presence of CTCs identified by the expression of CK-19 and c-erbB-2 in the peripheral blood mononuclear cell (PBMC) fraction by quantitative reverse transcription PCR (RT-PCR) and (b) the TGP, which was determined by analyzing the expression of 21 genes in paraffin-embedded tissue samples by quantitative multiplex RT-PCR with the Plexor® system. We observed a statistically significant correlation between the progression-free interval (PFI) and the clinical stage (p = 0.000701), the TGP score (p = 0.006538), and the presence of hormone receptors in the tumor (p = 0.0432). We observed no correlation between the PFI and the presence or absence of CK-19 or HER2 expression in the PBMC fraction prior to the start of treatment or in the two following readouts. Multivariate analysis revealed that only the TGP score significantly correlated with the PFI (p = 0.029247). The TGP is an important prognostic variable for patients with locoregional breast cancer. The presence of CTCs adds no prognostic value to the information already provided by the TGP. PMID:25976504

  2. 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

  3. Methylation profiling defines an extensive field defect in histologically normal prostate tissues associated with prostate cancer.

    PubMed

    Yang, Bing; Bhusari, Sachin; Kueck, Jessica; Weeratunga, Pushpa; Wagner, Jennifer; Leverson, Glen; Huang, Wei; Jarrard, David F

    2013-04-01

    Prostate cancer (PCa) is typically found as a multifocal disease suggesting the potential for molecular defects within the morphologically normal tissue. The frequency and spatial extent of DNA methylation changes encompassing a potential field defect are unknown. A comparison of non-tumor-associated (NTA) prostate to histologically indistinguishable tumor-associated (TA) prostate tissues detected a distinct profile of DNA methylation alterations (0.2%) using genome-wide DNA arrays based on the Encyclopedia of DNA Elements 18 sequence that tile both gene-rich and poor regions. Hypomethylation (87%) occurred more frequently than hypermethylation (13%). Several of the most significantly altered loci (CAV1, EVX1, MCF2L, and FGF1) were then used as probes to map the extent of these DNA methylation changes in normal tissues from prostates containing cancer. In TA tissues, the extent of methylation was similar both adjacent (2 mm) and at a distance (>1 cm) from tumor foci. These loci were also able to distinguish NTA from TA tissues in a validation set of patient samples. These mapping studies indicate that a spatially widespread epigenetic defect occurs in the peripheral prostate tissues of men who have PCa that may be useful in the detection of this disease. PMID:23555185

  4. 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

  5. Genomic Profiling of Thyroid Cancer Reveals a Role for Thyroglobulin in Metastasis.

    PubMed

    Siraj, Abdul K; Masoodi, Tariq; Bu, Rong; Beg, Shaham; Al-Sobhi, Saif S; Al-Dayel, Fouad; Al-Dawish, Mohammed; Alkuraya, Fowzan S; Al-Kuraya, Khawla S

    2016-06-01

    Papillary thyroid carcinoma (PTC) has a wide geographic variation in incidence; it is most common in Saudi Arabia, where it is only second to breast cancer as the most common cancer among females. Genomic profiling of PTC from Saudi Arabia has not been attempted previously. We performed whole-exome sequencing of 101 PTC samples and the corresponding genomic DNA to identify genes with recurrent somatic mutations, then sequenced these genes by using a next-generation gene-panel approach in an additional 785 samples. In addition to BRAF, N-RAS, and H-RAS, which have previously been shown to be recurrently mutated in PTC, our analysis highlights additional genes, including thyroglobulin (TG), which harbored somatic mutations in 3% of the entire cohort. Surprisingly, although TG mutations were not exclusive to mutations in the RAS-MAP kinase pathway, their presence was associated with a significantly worse clinical outcome, which suggests a pathogenic role beyond driving initial oncogenesis. Analysis of metastatic PTC tissue revealed significant enrichment for TG mutations (p < 0.001), including events of apparent clonal expansion. Our results suggest a previously unknown role of TG somatic mutations in the pathogenesis of PTC and its malignant evolution. PMID:27236916

  6. Cancer cell profiling by barcoding allows multiplexed protein analysis in fine needle aspirates

    PubMed Central

    Ullal, Adeeti V.; Peterson, Vanessa; Agasti, Sarit S.; Tuang, Suan; Juric, Dejan; Castro, Cesar M.; Weissleder, Ralph

    2014-01-01

    Immunohistochemistry-based clinical diagnoses require invasive core biopsies and use a limited number of protein stains to identify and classify cancers. Here, we introduce a technology that allows analysis of hundreds of proteins from minimally invasive fine needle aspirates (FNA), which contain much smaller numbers of cells than core biopsies. The method capitalizes on DNA-barcoded antibody sensing where barcodes can be photo-cleaved and digitally detected without any amplification steps. Following extensive benchmarking in cell lines, this method showed high reproducibility and achieved single cell sensitivity. We used this approach to profile ~90 proteins in cells from FNAs and subsequently map patient heterogeneity at the protein level. Additionally, we demonstrate how the method could be used as a clinical tool to identify pathway responses to molecularly targeted drugs and to predict drug response in patient samples. This technique combines specificity with ease of use to offer a new tool for understanding human cancers and designing future clinical trials. PMID:24431113

  7. 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

  8. 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

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

    PubMed

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

    2012-02-01

    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

  10. 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.

  11. Expression Profiling of Exosomal miRNAs Derived from Human Esophageal Cancer Cells by Solexa High-Throughput Sequencing

    PubMed Central

    Liao, Juan; Liu, Ran; Yin, Lihong; Pu, Yuepu

    2014-01-01

    Cellular genetic materials, such as microRNAs (miRNAs), mRNAs and proteins, are packaged inside exosomes, small membrane vesicles of endocytic origin that are released into the extracellular environment. These cellular genetic materials can be delivered into recipient cells, where they exert their respective biological effects. However, the miRNA profiles and biological functions of exosomes secreted by cancer cells remain unknown. The present study explored the miRNA expression profile and distribution characteristics of exosomes derived from human esophageal cancer cells through Solexa high-throughput sequencing. Results showed that 56,421 (2.94%) unique sequences in cells and 7727 (0.63%) in exosomes matched known miRNAs. A total of 342 and 48 known miRNAs were identified in cells and exosomes, respectively. Moreover, 64 and 32 novel miRNAs were predicted in cells and exosomes, respectively. Significant differences in miRNA expression profiles were found between human esophageal cancer cells and exosomes. These findings provided new insights into the characteristics of miRNAs in exosomes derived from human esophageal cancer cells and the specific roles of miRNAs in intercellular communication mediated by exosomes in esophageal cancer. PMID:25184951

  12. Proteomic Mucin Profiling for the Identification of Cystic Precursors of Pancreatic Cancer

    PubMed Central

    2014-01-01

    Background Pancreatic cystic lesions (PCLs) are increasingly frequent radiological incidentalomas, with a considerable proportion representing precursors of pancreatic cancer. Better diagnostic tools are required for patients to benefit from this development. Methods To evaluate whether cyst fluid mucin expression could predict malignant potential and/or transformation in PCLs, a proteomic method was devised and prospectively evaluated in consecutive patients referred to our tertiary center for endoscopic ultrasound-guided aspiration of cystic lesions from May 2007 through November 2008 (discovery cohort) and from December 2008 through October 2012 (validation cohort). Cytology and cyst fluid carcinoembryonic antigen (CEA; premalignancy > 192ng/mL, malignancy > 1000ng/mL) were routinely analyzed, and samples were further processed as follows: one-dimensional gel electrophoresis, excision of high-mass areas, tryptic digestion and nano-liquid chromatography–tandem mass spectrometry, with peptide identification by Mascot software and an in-house mucin database. All diagnostic evaluations were blinded to proteomics results. Histology was required to confirm the presence/absence of malignant transformation. All statistical tests were two-sided. Results Proteomic mucin profiling proved statistically significantly more accurate (97.5%; 95% confidence interval [CI] = 90.3% to 99.6%) than cytology (71.4%; 95% CI = 59.8% to 80.9%; P < .001) and cyst fluid CEA (78.0%; 95% CI = 65.0% to 87.3%; P < .001) in identifying the 37 (out of 79; 46.8%) lesions with malignant potential (ie, premalignant or malignant tumors). The accuracy of proteomics was nearly identical (96.6% vs 98.0%) between the discovery (n = 29) and validation (n = 50) cohorts. Furthermore, mucin profiling predicted malignant transformation, present in 16 out of 29 (discovery cohort: 9, validation cohort: 20) lesions with available histology, with 89.7% accuracy (95% CI = 71.5% to 97.3%) (for the validation

  13. Identifying Early Dehydration Risk With Home-Based Sensors During Radiation Treatment: A Feasibility Study on Patients With Head and Neck Cancer

    PubMed Central

    2013-01-01

    Background Systems that enable remote monitoring of patients’ symptoms and other health-related outcomes may optimize cancer care outside of the clinic setting. CYCORE (CYberinfrastructure for COmparative effectiveness REsearch) is a software-based prototype for a user-friendly cyberinfrastructure supporting the comprehensive collection and analyses of data from multiple domains using a suite of home-based and mobile sensors. This study evaluated the feasibility of using CYCORE to address early at-home identification of dehydration risk in head and neck cancer patients undergoing radiation therapy. Methods Head and neck cancer patients used home-based sensors to capture weight, blood pressure, pulse, and patient-reported outcomes for two 5-day periods during radiation therapy. Data were sent to the radiation oncologist of each head and neck cancer patient, who viewed them online via a Web-based interface. Feasibility outcomes included study completion rate, acceptability and perceived usefulness of the intervention, and adherence to the monitoring protocol. We also evaluated whether sensor data could identify dehydration-related events. Results Fifty patients consented to participate, and 48 (96%) completed the study. More than 90% of patients rated their ease, self-efficacy, and satisfaction regarding use of the sensor suite as extremely favorable, with minimal concerns expressed regarding data privacy issues. Patients highly valued the ability to have immediate access to objective, self-monitoring data related to personal risk for dehydration. Clinician assessments indicated a high degree of satisfaction with the ease of using the CYCORE system and the resulting ability to monitor their patients remotely. Conclusion Implementing CYCORE in a clinical oncology care setting is feasible and highly acceptable to both patients and providers. PMID:24395986

  14. 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 ... social workers, and patient advocates. Cancer.Net Guide Thyroid Cancer Overview Statistics Medical Illustrations Risk Factors Symptoms ...

  15. Breast Cancer

    MedlinePlus

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

  16. Anal Cancer

    MedlinePlus

    ... are here Home > Types of Cancer > Anal Cancer Anal Cancer This is Cancer.Net’s Guide to Anal Cancer. Use the menu below to choose the ... social workers, and patient advocates. Cancer.Net Guide Anal Cancer Introduction Statistics Risk Factors and Prevention Screening ...

  17. Human umbilical cord mesenchymal stem cells delivering sTRAIL home to lung cancer mediated by MCP-1/CCR2 axis and exhibit antitumor effects.

    PubMed

    Yan, Cihui; Song, Xinmiao; Yu, Wenwen; Wei, Feng; Li, Hui; Lv, Mengguo; Zhang, Xinwei; Ren, Xiubao

    2016-06-01

    Mesenchymal stem cells (MSCs) are believed to be a potential vehicle delivering antitumor agents for their tumor-homing capacity, while the underlying mechanism is yet to be explored. The apoptotic ligand TNF-related apoptosis-inducing ligand (TRAIL) has been suggested as a promising candidate for cancer gene therapy owing to its advantage of selectively inducing apoptosis in cancer cells while sparing normal cells. An isoleucine zipper (ISZ) added to the N-terminal of secretable soluble TRAIL (sTRAIL) can generate the trimeric form of TRAIL (ISZ-sTRAIL) and increase its antitumor potential. However, the inefficient delivery and toxicity are still obstacles for its use. In this study, the migration of human umbilical cord mesenchymal stem cells (HUMSCs) to lung cancer was observed through transwell migration assay and animal bioluminescent imaging both in vitro and in vivo. We found that the homing ability of HUMSCs was suppressed after either knocking down the expression of monocyte chemoattractant protein-1(MCP-1) in lung cancer cells or blocking CCR2 expressed on the surface of HUMSCs, indicating the important role of MCP-1/CCR2 axis in the tropism of HUMSCs to lung cancer. Furthermore, we genetically modified HUMSCs to deliver ISZ-sTRAIL to tumor sites specifically. This targeted therapeutic system exhibited promising apoptotic induction and antitumor potential in a xenograft mouse model without obvious side effects. In conclusion, HUMSCs expressing ISZ-sTRAIL might be an efficient therapeutic approach against lung cancer and MCP-1/CCR2 axis is essential for the tumor tropism of HUMSCs. PMID:26733169

  18. Drug transporter expression profiling in chemoresistant variants of the A2780 ovarian cancer cell line.

    PubMed

    Januchowski, Radosław; Zawierucha, Piotr; Ruciński, Marcin; Andrzejewska, Małgorzata; Wojtowicz, Karolina; Nowicki, Michał; Zabel, Maciej

    2014-05-01

    Ovarian cancer is characterized by the higher mortality among gynecological cancers. In results of MDR development during chemotherapy cancer cells become resistant to further treatment. Microarray techniques can provide information about MDR development at gene expression level. ABC and SLC transporters are most important proteins responsible for this phenomenon. In this study changes of ABC and SLC genes expression pattern in drugs resistant sublines of the A2780 ovarian cancer cell line were demonstrated. The cytostatic resistant sublines were generated by culture of A2780 cell line with an increasing concentration of the indicated drugs. As screening methods, we used Affymetrix U219 Human Genome microarrays. Independent t-tests were used to determinate statistical significances of results. Genes that expression levels were higher than assumed threshold (upregulated above threefold and downregulated under -3 fold) were visualized using scatter plot method, selected and listed in table. Between the ABC genes increased expression of seven genes and decreased expression of three genes were observed. Expression of two genes was increased or decreased depending on the cell line. We observed significant (more than tenfold) increase in expression of four ABC genes: ABCA8, ABCB1, ABCB4 and ABCG2 and decreased expression of ABCA3 gene. We also observed changes in expression of 32 SLC genes. Between them we observe increased expression of 17 genes and decreased expression of 15 genes. Expression of four genes was increased or decreased dependent on cell line. The expression of nine SLC genes increased or decreased very significantly (more than tenfold). Five genes were significantly upregulated: SLC2A9, SLC16A3, SLC16A14, SLC38A4 and SLC39A8. Four additional genes were significantly downregulated: SLC2A14, SLC6A15, SLC8A1 and SLC27A2. Expression profiles of these genes give strong arguments for assumption of correlation between expression of ABC and SLC genes and drug

  19. Lymphocytic infiltrate is associated with favorable biomarkers profile in HER2-overexpressing breast cancers and adverse biomarker profile in ER-positive breast cancers.

    PubMed

    Tsang, Julia Y S; Hui, Suen-Wah; Ni, Yun-Bi; Chan, Siu-Ki; Yamaguchi, Rin; Kwong, Ava; Law, Bonita K B; Tse, Gary M

    2014-01-01

    The value for lymphocytic infiltration (LI) has been increasingly recognized for tumor assessment. In breast cancer, however, the overall significance of LI remains poorly defined, probably due to its heterogeneity. A large cohort of breast cancer was evaluated for the degree of LI and its association with traditional pathologic factors, biomarker expression, and cancer subtypes. The number of CD8 cytotoxic effector and FoxP3 regulatory T cell (Treg) was evaluated in those cases with high LI. High LI was associated with negative ER and PR but positive HER2 and EGFR expression (p < 0.001 for all). In ER-positive cancers, high LI was associated with poor prognostic features including higher grade, the presence of necrosis, and lymphovascular invasion (LVI) (p = 0.007 for LVI and <0.001 for the others). Conversely, LI correlated with smaller tumor size, a good prognostic feature (p = 0.046) in HER2+ ER-cancers. These observations suggested LI may show opposite prognostic values in different breast cancer subgroups. Interestingly, when the phenotype of LI in these subgroups was evaluated, a strong positive association with intratumoral accumulation of Treg was found in ER-positive cancers (p = 0.003, Rs = 0.319), while the opposite was observed in HER2+ ER-cancers (p < 0.001, Rs = -0.427). Also, in ER-positive cancers, positive associations between peri- and intra-tumoral distribution were found with both CD8 and Tregs (CD8: p < 0.001, Rs = 0.547; Treg: p = 0.001, Rs = 0.460). Nonetheless, in HER2+ ER-cancers, such strong association was found with CD8 (p < 0.001, Rs = 0.766) but not Tregs. The results may implicate a differential intratumoral migration of LI in different subtypes of breast cancer. In summary, the clinical value of LI in breast cancers could be subtype-dependent. In ER-positive cancers, high LI correlated with biologic parameters associated with poor prognosis, whereas in HER2 positive cancers, LI correlated with biologic

  20. 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…

  1. Profiling of Discrete Gynecological Cancers Reveals Novel Transcriptional Modules and Common Features Shared by Other Cancer Types and Embryonic Stem Cells

    PubMed Central

    Jacob-Hirsch, Jasmine; Amariglio, Ninette; Vlachos, George D.; Loutradis, Dimitrios; Anagnou, Nicholas P.

    2015-01-01

    Studies on individual types of gynecological cancers (GCs), utilizing novel expression technologies, have revealed specific pathogenetic patterns and gene markers for cervical (CC), endometrial (EC) and vulvar cancer (VC). Although the clinical phenotypes of the three types of gynecological cancers are discrete, the fact they originate from a common embryological origin, has led to the hypothesis that they might share common features reflecting regression to early embryogenesis. To address this question, we performed a comprehensive comparative analysis of their profiles. Our data identified both common features (pathways and networks) and novel distinct modules controlling the same deregulated biological processes in all three types. Specifically, four novel transcriptional modules were discovered regulating cell cycle and apoptosis. Integration and comparison of our data with other databases, led to the identification of common features among cancer types, embryonic stem (ES) cells and the newly discovered cell population of squamocolumnar (SC) junction of the cervix, considered to host the early cancer events. Conclusively, these data lead us to propose the presence of common features among gynecological cancers, other types of cancers, ES cells and the pre-malignant SC junction cells, where the novel E2F/NFY and MAX/CEBP modules play an important role for the pathogenesis of gynecological carcinomas. PMID:26559525

  2. 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

  3. Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen

    PubMed Central

    Loi, Sherene; Haibe-Kains, Benjamin; Desmedt, Christine; Wirapati, Pratyaksha; Lallemand, Françoise; Tutt, Andrew M; Gillet, Cheryl; Ellis, Paul; Ryder, Kenneth; Reid, James F; Daidone, Maria G; Pierotti, Marco A; Berns, Els MJJ; Jansen, Maurice PHM; Foekens, John A; Delorenzi, Mauro; Bontempi, Gianluca; Piccart, Martine J; Sotiriou, Christos

    2008-01-01

    Background Estrogen receptor positive (ER+) breast cancers (BC) are heterogeneous with regard to their clinical behavior and response to therapies. The ER is currently the best predictor of response to the anti-estrogen agent tamoxifen, yet up to 30–40% of ER+BC will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance are required. We used gene expression profiling to develop an outcome-based predictor using a training set of 255 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy. We used clusters of highly correlated genes to develop our predictor to facilitate both signature stability and biological interpretation. Independent validation was performed using 362 tamoxifen-treated ER+ BC samples obtained from multiple institutions and treated with tamoxifen only in the adjuvant and metastatic settings. Results We developed a gene classifier consisting of 181 genes belonging to 13 biological clusters. In the independent set of adjuvantly-treated samples, it was able to define two distinct prognostic groups (HR 2.01 95%CI: 1.29–3.13; p = 0.002). Six of the 13 gene clusters represented pathways involved in cell cycle and proliferation. In 112 metastatic breast cancer patients treated with tamoxifen, one of the classifier components suggesting a cellular inflammatory mechanism was significantly predictive of response. Conclusion We have developed a gene classifier that can predict clinical outcome in tamoxifen-treated ER+ BC patients. Whilst our study emphasizes the important role of proliferation genes in prognosis, our approach proposes other genes and pathways that may elucidate further mechanisms that influence clinical outcome and prediction of response to tamoxifen. PMID:18498629

  4. 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

  5. [Three cases of lung cancer presenting with spinal cord paralysis as the initial manifestation-symptom control, nursing care, and coordination of home medical care].

    PubMed

    Isono, Hisayo; Hayakawa, Naoko; Inoue, Akiko; Onose, Akira

    2013-12-01

    Bone metastasis from lung cancer accounts for approximately 30% of all metastatic bone tumors. The median survival time of patients with stage IV lung cancer with bone metastases is 5.5 months and that of patients without bone metastases is 7.5 months. Here, we report 3 cases of spinal cord paralysis. All cases were assessed according to the Tokuhashi score. As the predicted survival time of these patients was < or = 6 months, we opted for conservative treatment. We administered chemotherapy and radiation therapy, ensured symptom control, provided nursing care (prevention of decubitus, position changing, defecation control, rehabilitation, and mental health care), and coordinated home medical care. Patient management was mediated by a multidisciplinary medical team. However, all 3 patients were unable to return home and died in the hospital within 1-2 months after the onset of spinal cord paralysis. Spinal metastases can be expected not only in patients with lung cancer but also in patients with other types of carcinomas. Early diagnosis and treatment and accurate prognosis prediction are essential. Rapid responses and cooperation from experts are required, and increased awareness regarding spinal metastases among health professionals is essential. PMID:24712141

  6. Immunohistochemical, genetic and epigenetic profiles of hereditary and triple negative breast cancers. Relevance in personalized medicine

    PubMed Central

    Murria, Rosa; Palanca, Sarai; de Juan, Inmaculada; Alenda, Cristina; Egoavil, Cecilia; Seguí, Francisco J; García-Casado, Zaida; Juan, María J; Sánchez, Ana B; Segura, Ángel; Santaballa, Ana; Chirivella, Isabel; Llop, Marta; Pérez, Gema; Barragán, Eva; Salas, Dolores; Bolufer, Pascual

    2015-01-01

    This study aims to identify the profile of immunohistochemical (IHC) parameters, copy number aberrations (CNAs) and epigenetic alterations [promoter methylation (PM) and miR expression] related to hereditary (H) and triple negative (TN) breast cancer (BC). This profile could be of relevance for guiding tumor response to treatment with targeting therapy. The study comprises 278 formalin fixed paraffin-embedded BCs divided into two groups: H group, including 88 hereditary BC (HBC) and 190 non hereditary (NHBC), and TN group, containing 79 TNBC and 187 non TNBC (NTNBC). We assessed IHC parameters (Ki67, ER, PR, HER2, CK5/6, CK18 and Cadherin-E), CNA of 20 BC related genes, and PM of 24 tumor suppressor genes employing MLPA/MS-MLPA (MRC Holland, Amsterdam). MiR-4417, miR-423-3p, miR-590-5p and miR-187-3p expression was assessed by quantitative RT-PCR (Applied Biosystems). Binary logistic regression was applied to select the parameters that better differentiate the HBC or TN groups. For HBC we found that, ER expression, ERBB2 CNA and PM in RASSF1 and TIMP3 were associated with NHBC whereas; MYC and AURKA CNA were linked to HBC. For TNBC, we found that CDC6 CNA, GSTP1 and RASSF1 PM and miR-423-3p hyperexpression were characteristic of NTNBC, while MYC aberrations, BRCA1 hypermethylation and miR-590-5p and miR-4417 hyperexpression were more indicative of TNBC. The selected markers allow establishing BC subtypes, which are characterized by showing similar etiopathogenetic mechanisms, some of them being molecular targets for known drugs or possible molecular targets. These results could be the basis to implement a personalized therapy. PMID:26328265

  7. 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 ...

  8. Ruguo key genes and tumor driving factors identification of bladder cancer based on the RNA-seq profile

    PubMed Central

    Zhang, Minglei; Li, Hongyan; Zou, Di; Gao, Ji

    2016-01-01

    Aim This study aimed to select several signature genes associated with bladder cancer, thus to investigate the possible mechanism in bladder cancer. Methods The mRNA expression profile data of GSE31614, including ten bladder tissues and ten control samples, was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) in bladder cancer samples compared with the control samples were screened using the Student’s t-test method. Functional analysis for the DEGs was analyzed using the Database for Annotation, Visualization, and Integrated Discovery from the Gene Ontology database, followed by the transcription function annotation of DEGs from Tumor-Associated Gene database. Motifs of genes that had transcription functions in promoter region were analyzed using the Seqpos. Results A total of 1,571 upregulated and 1,507 downregulated DEGs in the bladder cancer samples were screened. ELF3 and MYBL2 involved in cell cycle and DNA replication were tumor suppressors. MEG3, APEX1, and EZH2 were related with the cell epigenetic regulation in bladder cancer. Moreover, HOXB9 and EN1 that have their own motif were the transcription factors. Conclusion Our study has identified several key genes involved in bladder cancer. ELF3 and MYBL2 are tumor suppressers, HOXB9 and EN1 are the main regulators, while MEG3, APEX1, and EZH2 are driving factors for bladder cancer progression. PMID:27217782

  9. “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

  10. "Picking up the pieces" - Meanings of receiving home nursing care when being old and living with advanced cancer in a rural area.

    PubMed

    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

  11. 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

  12. Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing

    PubMed Central

    Zhou, Jerry; Belov, Larissa; Solomon, Michael J.; Chan, Charles; Clarke, Stephen J.; Christopherson, Richard I.

    2011-01-01

    The current prognosis and classification of CRC relies on staging systems that integrate histopathologic and clinical findings. However, in the majority of CRC cases, cell dysfunction is the result of numerous mutations that modify protein expression and post-translational modification1. A number of cell surface antigens, including cluster of differentiation (CD) antigens, have been identified as potential prognostic or metastatic biomarkers in CRC. These antigens make ideal biomarkers as their expression often changes with tumour progression or interactions with other cell types, such as tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs). The use of immunohistochemistry (IHC) for cancer sub-classification and prognostication is well established for some tumour types2,3. However, no single ‘marker’ has shown prognostic significance greater than clinico-pathological staging or gained wide acceptance for use in routine pathology reporting of all CRC cases. A more recent approach to prognostic stratification of disease phenotypes relies on surface protein profiles using multiple 'markers'. While expression profiling of tumours using proteomic techniques such as iTRAQ is a powerful tool for the discovery of biomarkers4, it is not optimal for routine use in diagnostic laboratories and cannot distinguish different cell types in a mixed population. In addition, large amounts of tumour tissue are required for the profiling of purified plasma membrane glycoproteins by these methods. In this video we described a simple method for surface proteome profiling of viable cells from disaggregated CRC samples using a DotScan CRC antibody microarray. The 122-antibody microarray consists of a standard 82-antibody region recognizing a range of lineage-specific leukocyte markers, adhesion molecules, receptors and markers of inflammation and immune response5, together with a satellite region for detection of 40 potentially prognostic markers for CRC

  13. Mouse skin tumorigenicity studies of indoor coal and wood combustion emissions from homes of residents in Xuan Wei, China with high lung cancer mortality

    SciTech Connect

    Mumford, J.L.; Helmes, C.T.; Lee, X.; Seidenberg, J.; Nesnow, S.

    1990-01-01

    The rural Xuan Wei County, Yunnan Province, China, has an unusually high lung cancer mortality rate that cannot be attributed to tobacco smoke or occupational exposure. The lung cancer rate is associated with 'smoky' coal, in contrast to wood or 'smokeless' coal burned in unventilated homes. The study was conducted to characterize and compare mouse skin tumorigenicity of the coal and the wood combustion emissions and to link the resulting animal data to human lung cancer. Indoor air particles were collected from a central commune where the lung cancer mortality rate is high and smoky coal is the major fuel used, and also from a south western commune where lung cancer mortality rate is low and wood and smokeless coal are the major fuels used. The organic extracts of these indoor air particles were analyzed for polycyclic aromatic hydrocarbons (PAHs) and assayed for skin tumor initiation activity and complete carcinogenicity in SENCAR mice. Mouse skin was initiated with 1,2,5,10, and 20 mg of organic extracts of the emission particles during the first week, and one week after initiation the mice were promoted with 12-0-tetradecanoylphorbol-13-acetate (TPA, 2 microgram/mouse) applied topically twice a week for 26 weeks. The results showed that the smoky coal sample is the most active among the three combustion emission samples.

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

    PubMed Central

    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. PMID:26727311

  15. Somatic mutation profiling of follicular thyroid cancer by next generation sequencing.

    PubMed

    Swierniak, Michal; Pfeifer, Aleksandra; Stokowy, Tomasz; Rusinek, Dagmara; Chekan, Mykola; Lange, Dariusz; Krajewska, Jolanta; Oczko-Wojciechowska, Małgorzata; Czarniecka, Agnieszka; Jarzab, Michal; Jarzab, Barbara; Wojtas, Bartosz

    2016-09-15

    The molecular etiology of follicular thyroid tumors is largely unknown, rendering the diagnostics of these tumors challenging. The somatic alterations present in these tumors apart from RAS gene mutations and PAX8/PPARG translocations are not well described. To evaluate the profile of somatic alteration in follicular thyroid tumors, a total of 82 thyroid tissue samples derived from 48 patients were subjected to targeted Illumina HiSeq next generation sequencing of 372 cancer-related genes. New somatic alterations were identified in oncogenes (MDM2, FLI1), transcription factors and repressors (MITF, FLI1, ZNF331), epigenetic enzymes (KMT2A, NSD1, NCOA1, NCOA2), and protein kinases (JAK3, CHEK2, ALK). Single nucleotide and large structural variants were most and least frequently identified, respectively. A novel translocation in DERL/COX6C was detected. Many somatic alterations in non-coding gene regions with high penetrance were observed. Thus, follicular thyroid tumor somatic alterations exhibit complex patterns. Most tumors contained distinct somatic alterations, suggesting previously unreported heterogeneity. PMID:27283500

  16. Primary breast lymphoma: Patient profile, outcome and prognostic factors. A multicentre Rare Cancer Network study

    PubMed Central

    Jeanneret-Sozzi, Wendy; Taghian, Alphonse; Epelbaum, Ron; Poortmans, Philip; Zwahlen, Daniel; Amsler, Beat; Villette, Sylviane; Belkacémi, Yazid; Nguyen, Tan; Scalliet, Pierre; Maingon, Philippe; Gutiérrez, Cristina; Gastelblum, Pauline; Krengli, Marco; Raad, Rita Abi; Ozsahin, Mahmut; Mirimanoff, René-Olivier

    2008-01-01

    Background To asses the clinical profile, treatment outcome and prognostic factors in primary breast lymphoma (PBL). Methods Between 1970 and 2000, 84 consecutive patients with PBL were treated in 20 institutions of the Rare Cancer Network. Forty-six patients had Ann Arbor stage IE, 33 stage IIE, 1 stage IIIE, 2 stage IVE and 2 an unknown stage. Twenty-one underwent a mastectomy, 39 conservative surgery and 23 biopsy; 51 received radiotherapy (RT) with (n = 37) or without (n = 14) chemotherapy. Median RT dose was 40 Gy (range 12–55 Gy). Results Ten (12%) patients progressed locally and 43 (55%) had a systemic relapse. Central nervous system (CNS) was the site of relapse in 12 (14%) cases. The 5-yr overall survival, lymphoma-specific survival, disease-free survival and local control rates were 53%, 59%, 41% and 87% respectively. In the univariate analyses, favorable prognostic factors were early stage, conservative surgery, RT administration and combined modality treatment. Multivariate analysis showed that early stage and the use of RT were favorable prognostic factors. Conclusion The outcome of PBL is fair. Local control is excellent with RT or combined modality treatment but systemic relapses, including that in the CNS, occurs frequently. PMID:18380889

  17. Molecular mechanisms associated with breast cancer based on integrated gene expression profiling by bioinformatics analysis.

    PubMed

    Wu, Di; Han, Bing; Guo, Liang; Fan, Zhimin

    2016-07-01

    In this study, we aimed to gain more insights into the underlying molecular mechanisms responsible for breast cancer (BC) progression. Three gene expression profiles of human BC were integrated and used to screen the differentially expressed genes (DEGs) between healthy breast samples and BC samples. Protein-protein interaction (PPI) network of DEGs was constructed by mapping DEGs into the Search Tool for the Retrieval of Interacting Genes (STRING) database; then the subnetworks of PPI were constructed with plug-in, MCODE and DEGs in Subnetwork 1 were analysed based on Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway database ( http://www.genome.jp/kegg /). In addition, co-expression network of DEGs was established using the Cytoscape. Totalally 931 DEGs were selected, including 340 up-regulated genes and 591 down-regulated genes. KEGG pathway analysis for DEGs in Subnetwork 1 showed that the pathogenesis of BC was associated with cell cycle, oocyte meiosis, progesterone-mediated oocyte maturation and p53 signalling pathways. Meanwhile, the most significant-related DEGs were found by co-expression network analysis of DEGs. In conclusion, CCNG1 might be involved in the progression of BC via inhibiting cell proliferation, and ADAMTS1 might play a crucial role in BC development through the regulation of angiogenesis. PMID:26804550

  18. 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

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

    PubMed

    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

  20. 6 Common Cancers - Prostate Cancer

    MedlinePlus

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

  1. 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 ...

  2. 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

  3. Exon-Level Transcriptome Profiling in Murine Breast Cancer Reveals Splicing Changes Specific to Tumors with Different Metastatic Abilities

    PubMed Central

    Bemmo, Amandine; Dias, Christel; Rose, April A. N.; Russo, Caterina; Siegel, Peter; Majewski, Jacek

    2010-01-01

    Background Breast cancer is the second most frequent type of cancer affecting women. We are increasingly aware that changes in mRNA splicing are associated with various characteristics of cancer. The most deadly aspect of cancer is metastasis, the process by which cancer spreads from the primary tumor to distant organs. However, little is known specifically about the involvement of alternative splicing in the formation of macroscopic metastases. Our study investigates transcript isoform changes that characterize tumors of different abilities to form growing metastases. Methods and Findings To identify alternative splicing events (ASEs) that are associated with the fully metastatic phenotype in breast cancer, we used Affymetrix Exon Microarrays to profile mRNA isoform variations genome-wide in weakly metastatic (168FARN and 4T07) and highly metastatic (4T1) mammary carcinomas. Statistical analysis identified significant expression changes in 7606 out of 155,994 (4%) exons and in 1725 out of 189,460 (1%) intronic regions, which affect 2623 out of 16,654 (16%) genes. These changes correspond to putative alternative isoforms—several of which are novel—that are differentially expressed between tumors of varying metastatic phenotypes. Gene pathway analysis showed that 1224 of genes expressing alternative isoforms were involved in cell growth, cell interactions, cell proliferation, cell migration and cell death and have been previously linked to cancers and genetic disorders. We chose ten predicted splice variants for RT-PCR validation, eight of which were successfully confirmed (MED24, MFI2, SRRT, CD44, CLK1 and HNRNPH1). These include three novel intron retentions in CD44, a gene in which isoform variations have been previously associated with the metastasis of several cancers. Conclusion Our findings reveal that various genes are differently spliced and/or expressed in association with the metastatic phenotype of tumor cells. Identification of metastasis

  4. The Ovarian Cancer Chemokine Landscape is Conducive to Homing of Vaccine-primed and CD3/CD28 Costimulated T cells Prepared for Adoptive Therapy

    PubMed Central

    Zsiros, Emese; Duttagupta, Priyanka; Dangaj, Denarda; Li, Hongzhe; Frank, Renee; Garrabrant, Thomas; Hagemann, Ian S.; Levine, Bruce L.; June, Carl H.; Zhang, Lin; Wang, Ena; Marincola, Francesco M.; Bedognetti, Davide; Powell, Daniel J.; Tanyi, Janos; Feldman, Michael D.; Kandalaft, Lana E.; Coukos, George

    2016-01-01

    Purpose Chemokines are implicated in T cell trafficking. We mapped the chemokine landscape in advanced stage ovarian cancer and characterized the expression of cognate receptors in autologous DC-vaccine primed T cells in the context of cell-based immunotherapy. Experimental design The expression of all known human chemokines in patients with primary ovarian cancer was analyzed on two independent microarray datasets and validated on tissue microarray. Peripheral blood T cells from five HLA-A2 patients with recurrent ovarian cancer, who previously received autologous tumor DC vaccine, underwent CD3/CD28 costimulation and expansion ex vivo. Tumor-specific T cells were identified by HER2/neu pentamer staining and were evaluated for the expression and functionality of chemokine receptors important for homing to ovarian cancer. Results The chemokine landscape of ovarian cancer is heterogeneous with high expression of known lymphocyte-recruiting chemokines (CCL2, CCL4 and CCL5) in tumors with intraepithelial T cells, whereas CXCL10, CXCL12 and CXCL16 are expressed quasi-universally, including in tumors lacking tumor infiltrating T cells. DC-vaccine primed T cells were found to express the cognate receptors for the above chemokines. Ex vivo CD3/CD28 costimulation and expansion of vaccine-primed T cells upregulated CXCR3 and CXCR4, and enhanced their migration toward universally expressed chemokines in ovarian cancer. Conclusions DC-primed tumor specific T cells are armed with the appropriate receptors to migrate towards universal ovarian cancer chemokines, and these receptors are further upregulated by ex vivo CD3/CD28 costimulation, which render T cells more fit for migrating towards these chemokines. PMID:25712684

  5. Gene Expression Profile for Predicting Survival in Advanced-Stage Serous Ovarian Cancer Across Two Independent Datasets

    PubMed Central

    Yoshihara, Kosuke; Tajima, Atsushi; Yahata, Tetsuro; Kodama, Shoji; Fujiwara, Hiroyuki; Suzuki, Mitsuaki; Onishi, Yoshitaka; Hatae, Masayuki; Sueyoshi, Kazunobu; Fujiwara, Hisaya; Kudo, Yoshiki; Kotera, Kohei; Masuzaki, Hideaki; Tashiro, Hironori; Katabuchi, Hidetaka; Inoue, Ituro; Tanaka, Kenichi

    2010-01-01

    Background Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer. Methodology/Principal Findings Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66–5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20–1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008). Conclusions/Significance The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer. PMID:20300634

  6. Metabolic Profiling-based Data-mining for an Effective Chemical Combination to Induce Apoptosis of Cancer Cells

    PubMed Central

    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

    2015-01-01

    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. PMID:25824377

  7. Home Hemodialysis

    MedlinePlus

    ... Organizations​​ . (PDF, 345 KB)​​​​​ Alternate Language URL Home Hemodialysis Page Content On this page: What is home ... Points to Remember Clinical Trials What is home hemodialysis? Home hemodialysis is hemodialysis that a person can ...

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

    PubMed

    Heyn, Holger; Carmona, F Javier; Gomez, Antonio; Ferreira, Humberto J; Bell, Jordana T; Sayols, Sergi; Ward, Kirsten; Stefansson, Olafur A; Moran, Sebastian; Sandoval, Juan; Eyfjord, Jorunn E; Spector, Tim D; 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

  9. 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

  10. AB053. MicroRNA expression profile in penile cancer revealed by next-generation small RNA sequencing

    PubMed Central

    Zhang, Li; Wei, Pengfei

    2016-01-01

    Objective 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. Methods 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. Results 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 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. Conclusions 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

  11. 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. PMID:25847643

  12. A qualitative investigation of the roles and perspectives of older patients with advanced cancer and their family caregivers in managing pain in the home

    PubMed Central

    2014-01-01

    Background Pain in advanced cancer is complex and multifaceted. In older patients comorbidities and age-related functional decline add to the difficulties in managing cancer pain. The current emphasis on care in the community, and preference by patients with life-limiting disease to receive care in the home, has meant that patients and their family caregivers have become increasingly responsible for the day-to-day management of cancer pain. An appreciation of patients’ and caregivers’ roles and perspectives managing pain is, therefore, fundamental to addressing cancer pain in this setting. Consequently, we sought to explore and describe their perspectives and roles. Methods A qualitative descriptive approach was used. Semi-structured interviews were conducted with a purposeful sample of patient- family caregiver dyads. Participants included 18 patients aged 65 years and over, with advanced cancer, receiving palliative care at home, and 15 family caregivers. The interview data were analysed using thematic analyses. Strategies were used to establish rigour. Results Two main themes were identified. The first theme, "Communicating the pain", represented pain assessment and incorporated four subthemes in which participants described: their roles in pain assessment, the identification and expression of pain, and the communication of pain between patients and caregivers. The second theme, "Finding a solution", comprised of four subthemes that reflected participants’ roles and approaches in controlling pain; as well as their beliefs about cancer pain control, experience with side effects, and perspectives on the goals of treatment. Conclusions The findings support other studies in identifying knowledge and attitudinal barriers to pain control; while adding to the literature by highlighting practical and relational barriers faced by older patients and their family caregivers. Health care professionals can do much to address the barriers identified by: correcting

  13. Multiplex Flow Cytometry Barcoding and Antibody Arrays Identify Surface Antigen Profiles of Primary and Metastatic Colon Cancer Cell Lines

    PubMed Central

    Sukhdeo, Kumar; Paramban, Rosanto I.; Vidal, Jason G.; Elia, Jeanne; Martin, Jody; Rivera, Maricruz; Carrasco, Daniel R.; Jarrar, Awad; Kalady, Matthew F.; Carson, Christian T.; Balderas, Robert; Hjelmeland, Anita B.; Lathia, Justin D.; Rich, Jeremy N.

    2013-01-01

    Colon cancer is a deadly disease affecting millions of people worldwide. Current treatment challenges include management of disease burden as well as improvements in detection and targeting of tumor cells. To identify disease state-specific surface antigen signatures, we combined fluorescent cell barcoding with high-throughput flow cytometric profiling of primary and metastatic colon cancer lines (SW480, SW620, and HCT116). Our multiplexed technique offers improvements over conventional methods by permitting the simultaneous and rapid screening of cancer cells with reduced effort and cost. The method uses a protein-level analysis with commercially available antibodies on live cells with intact epitopes to detect potential tumor-specific targets that can be further investigated for their clinical utility. Multiplexed antibody arrays can easily be applied to other tumor types or pathologies for discovery-based approaches to target identification. PMID:23308131

  14. 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: ...

  15. Genome-Wide Uncovering of STAT3-Mediated miRNA Expression Profiles in Colorectal Cancer Cell Lines

    PubMed Central

    Zhang, Jufeng; Luo, Xia; Li, Huiming; Deng, Ling

    2014-01-01

    Colorectal cancer (CRC) is one of the most common malignancies resulting in high mortality worldwide. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor which is frequently activated and aberrantly expressed in CRC. MicroRNAs (miRNAs) are a class of small noncoding RNAs which play important roles in many cancers. However, little is known about the global miRNA profiles mediated by STAT3 in CRC cells. In the present study, we applied RNA interference to inhibit STAT3 expression and profiled the miRNA expression levels regulated by STAT3 in CRC cell lines with deep sequencing. We found that 26 and 21 known miRNAs were significantly overexpressed and downexpressed, respectively, in the STAT3-knockdown CRC cell line SW480 (SW480/STAT3-siRNA) compared to SW480 transfected with scrambled siRNAs (SW480/siRNA-control). The miRNA expression profiling was then validated by quantitative real-time PCR for selected known miRNAs. We further predicted the putative target genes for the dysregulated miRNAs and carried out functional annotation including GO enrichment and KEGG pathway analysis for selected miRNA targets. This study directly depicts STAT3-mediated miRNA profiles in CRC cells, which provides a possible way to discover biomarkers for CRC therapy. PMID:25126546

  16. 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

  17. A Novel Multivariate Index for Pancreatic Cancer Detection Based On the Plasma Free Amino Acid Profile

    PubMed Central

    Fukutake, Nobuyasu; Ueno, Makoto; Hiraoka, Nobuyoshi; Shimada, Kazuaki; Shiraishi, Koichi; Saruki, Nobuhiro; Ito, Toshifumi; Yamakado, Minoru; Ono, Nobukazu; Imaizumi, Akira; Kikuchi, Shinya; Yamamoto, Hiroshi; Katayama, Kazuhiro

    2015-01-01

    Background The incidence of pancreatic cancer (PC) continues to increase in the world, while most patients are diagnosed with advanced stages and survive <12 months. This poor prognosis is attributable to difficulty of early detection. Here we developed and evaluated a multivariate index composed of plasma free amino acids (PFAAs) for early detection of PC. Methods We conducted a cross-sectional study in multi-institutions in Japan. Fasting plasma samples from PC patients (n = 360), chronic pancreatitis (CP) patients (n = 28), and healthy control (HC) subjects (n = 8372) without apparent cancers who were undergoing comprehensive medical examinations were collected. Concentrations of 19 PFAAs were measured by liquid chromatography–mass spectrometry. We generated an index consisting of the following six PFAAs: serine, asparagine, isoleucine, alanine, histidine, and tryptophan as variables for discrimination in a training set (120 PC and matching 600 HC) and evaluation in a validation set (240 PC, 28 CP, and 7772 HC). Results Several amino acid concentrations in plasma were significantly altered in PC. Plasma tryptophan and histidine concentrations in PC were particularly low, while serine was particularly higher than that of HC. The area under curve (AUC) based on receiver operating characteristic (ROC) curve analysis of the resulting index to discriminate PC from HC were 0.89 [95% confidence interval (CI), 0.86–0.93] in the training set. In the validation set, AUCs based on ROC curve analysis of the PFAA index were 0.86 (95% CI, 0.84–0.89) for all PC patients versus HC subjects, 0.81 (95% CI, 0.75–0.86) for PC patients from stage IIA to IIB versus HC subjects, and 0.87 (95% CI, 0.80–0.93) for all PC patients versus CP patients. Conclusions These findings suggest that the PFAA profile of PC was significantly different from that of HC. The PFAA index is a promising biomarker for screening and diagnosis of PC. PMID:26133769

  18. 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

  19. NCI Designated Cancer Centers

    MedlinePlus

    ... Laboratory for Cancer Research Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer ... Cancer Center History Frederick National Laboratory for Cancer Research Partners ... Profiles in Cancer Research Outstanding Investigator Award Recipients ...

  20. 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

  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. PMID:25524488

  2. 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

  3. 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

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

    PubMed

    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

  5. Care homes. Home truths.

    PubMed

    Schneider, J; Netten, A; Mozley, C; Levin, E; Mann, A; Blizard, B; Topan, C; Abbey, A; Kharicha, K; Todd, C

    1998-01-15

    Proposed joint inspectorates of care homes open the way for health input into residential care. An investigation into quality-of-care measures concluded that health professionals should be included in inspectorate teams, particularly in view of the increasing dependency of residents. No association was shown between cost and quality, but higher costs were associated with short-term car provision. When costing residential care, the impact on community and primary healthcare services may need to be taken into account. PMID:10176463

  6. 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

  7. Secondary electrospray ionization-mass spectrometry and a novel statistical bioinformatic approach identifies a cancer-related profile in exhaled breath of breast cancer patients: a pilot study.

    PubMed

    Martinez-Lozano Sinues, Pablo; Landoni, Elena; Miceli, Rosalba; Dibari, Vincenza F; Dugo, Matteo; Agresti, Roberto; Tagliabue, Elda; Cristoni, Simone; Orlandi, Rosaria

    2015-09-01

    Breath analysis represents a new frontier in medical diagnosis and a powerful tool for cancer biomarker discovery due to the recent development of analytical platforms for the detection and identification of human exhaled volatile compounds. Statistical and bioinformatic tools may represent an effective complement to the technical and instrumental enhancements needed to fully exploit clinical applications of breath analysis. Our exploratory study in a cohort of 14 breast cancer patients and 11 healthy volunteers used secondary electrospray ionization-mass spectrometry (SESI-MS) to detect a cancer-related volatile profile. SESI-MS full-scan spectra were acquired in a range of 40-350 mass-to-charge ratio (m/z), converted to matrix data and analyzed using a procedure integrating data pre-processing for quality control, and a two-step class prediction based on machine-learning techniques, including a robust feature selection, and a classifier development with internal validation. MS spectra from exhaled breath showed an individual-specific breath profile and high reciprocal homogeneity among samples, with strong agreement among technical replicates, suggesting a robust responsiveness of SESI-MS. Supervised analysis of breath data identified a support vector machine (SVM) model including 8 features corresponding to m/z 106, 126, 147, 78, 148, 52, 128, 315 and able to discriminate exhaled breath from breast cancer patients from that of healthy individuals, with sensitivity and specificity above 0.9.Our data highlight the significance of SESI-MS as an analytical technique for clinical studies of breath analysis and provide evidence that our noninvasive strategy detects volatile signatures that may support existing technologies to diagnose breast cancer. PMID:26390050

  8. Computational analysis of image-based drug profiling predicts synergistic drug combinations: applications in triple-negative breast cancer.

    PubMed

    Brandl, Miriam B; Pasquier, Eddy; Li, Fuhai; Beck, Dominik; Zhang, Sufang; Zhao, Hong; Kavallaris, Maria; Wong, Stephen T C

    2014-12-01

    An imaged-based profiling and analysis system was developed to predict clinically effective synergistic drug combinations that could accelerate the identification of effective multi-drug therapies for the treatment of triple-negative breast cancer and other challenging malignancies. The identification of effective drug combinations for the treatment of triple-negative breast cancer (TNBC) was achieved by integrating high-content screening, computational analysis, and experimental biology. The approach was based on altered cellular phenotypes induced by 55 FDA-approved drugs and biologically active compounds, acquired using fluorescence microscopy and retained in multivariate compound profiles. Dissimilarities between compound profiles guided the identification of 5 combinations, which were assessed for qualitative interaction on TNBC cell growth. The combination of the microtubule-targeting drug vinblastine with KSP/Eg5 motor protein inhibitors monastrol or ispinesib showed potent synergism in 3 independent TNBC cell lines, which was not substantiated in normal fibroblasts. The synergistic interaction was mediated by an increase in mitotic arrest with cells demonstrating typical ispinesib-induced monopolar mitotic spindles, which translated into enhanced apoptosis induction. The antitumour activity of the combination vinblastine/ispinesib was confirmed in an orthotopic mouse model of TNBC. Compared to single drug treatment, combination treatment significantly reduced tumour growth without causing increased toxicity. Image-based profiling and analysis led to the rapid discovery of a drug combination effective against TNBC in vitro and in vivo, and has the potential to lead to the development of new therapeutic options in other hard-to-treat cancers. PMID:24997502

  9. Expression profiles of inhibitor of growth protein 2 in normal and cancer tissues: An immunohistochemical screening analysis.

    PubMed

    Zhao, Shuang; Yang, Xue-Feng; Gou, Wen-Feng; Lu, Hang; Li, Hua; Zhu, Zhi-Tu; Sun, Hong-Zhi; Zheng, Hua-Chuan

    2016-02-01

    Inhibitor of growth protein 2 (ING2) has an important role in the regulation of chromatin remodeling, cell proliferation, cell‑cycle arrest, senescence and apoptosis. The present study performed an immunohistochemical analysis for expression profiling of ING2 protein in an array of tissues comprising normal mouse and human tissues, as well as human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung (n=192) carcinoma tissues. In mouse tissues, ING2 was detected in the nuclei and cytoplasm of the glandular epithelium of breast, hepatocytes, intestine, bronchium and alveoli, as well as the squamous epithelium of skin and glomeruli, and in myocardial cells, while it was located in the cytoplasm of renal tubules and striated muscle cells. ING2 protein was scattered in the brain and spleen. In human tissues, ING2 protein was principally distributed in the cytoplasm, while in it was present in the cytoplasm and nuclei in the stomach, intestine, cervix, endometrium trachea, breast and pancreas. The nuclear location of ING2 in the stomach was more prominent than that in the cytoplasm. High ING2 immunoreactivity was detected in the tongue, stomach, skin, pancreas, cervix and breast, whereas weakly in the brain stem, thymus, thyroid, lung, striated muscle, testis, bladder and ovary. In total, 617 out of 1,194 of the tested cancer tissues (51.7%) were ING2-positive. In most cases, ING2 expression was found to be restricted to the cytoplasm of all cancer tissues, while in certain cancer types, including renal clear cell, ovarian and colorectal carcinoma, it was occasionally present in the nuclei. Among the cancer tissues examined, ING2 was most frequently expressed in breast cancer (67.4%) and gynecological cancer types, including ovarian cancer (61.5%) and endometrial cancer (57.3%). Compared with

  10. Bisphenol A modulates colorectal cancer protein profile and promotes the metastasis via induction of epithelial to mesenchymal transitions.

    PubMed

    Chen, Zhuo-Jia; Yang, Xiang-Ling; Liu, Hao; Wei, Wei; Zhang, Kun-Shui; Huang, Hong-Bin; Giesy, John P; Liu, Huan-Liang; Du, Jun; Wang, Hong-Sheng

    2015-08-01

    More and more evidences indicate that endocrine disruptor chemicals such as bisphenol A (BPA) can act as carcinogens and enhance susceptibility to tumorigenesis. Although the gut is in direct contact with orally ingested BPA, effects of BPA on occurrence and development of colorectal cancer remain an unexplored endpoint. Colorectal cancer SW480 cells treated with nanomolar (10(-8) M) or greater (10(-5) M) concentrations of BPA were compared with responses of a control group. Proteomic study revealed that more than 56 proteins were modulated following exposure to BPA, which are relevant to structure, motility and proliferation of cells, production of ATP, oxidative stress, and protein metabolism. Further studies revealed that BPA increased migration and invasion and triggered transformations from epithelial to mesenchymal transitions (EMTs) of colorectal cancer cells, which was characterized by acquiring mesenchymal spindle-like morphology and increasing the expression of N-cadherin with a concomitant decrease of E-cadherin. Accordingly, BPA treatment increased the expression of transcription factor Snail. Furthermore, signal AKT/GSK-3β-mediated stabilization of Snail is involved during BPA-induced EMT of colon cancer cells. Our study first demonstrated that the xenoestrogen BPA at nanomolar and greater concentrations modulates the protein profiles and promotes the metastasis of colorectal cancer cells via induction of EMT. PMID:25119493

  11. 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

  12. Gene expression profiles of bladder cancers: evidence for a striking effect of in vitro cell models on gene patterns

    PubMed Central

    Dangles, V; Lazar, V; Validire, P; Richon, S; Wertheimer, M; Laville, V; Janneau, J-L; Barrois, M; Bovin, C; Poynard, T; Vallancien, G; Bellet, D

    2002-01-01

    In order to assess the effect of in vitro models on the expression of key genes known to be implicated in the development or progression of cancer, we quantified by real-time quantitative PCR the expression of 28 key genes in three bladder cancer tissue specimens and in their derived cell lines, studied either as one-dimensional single cell suspensions, two-dimensional monolayers or three-dimensional spheroids. Global analysis of gene expression profiles showed that in vitro models had a dramatic impact upon gene expression. Remarkably, quantitative differences in gene expression of 2–63-fold were observed in 24 out of 28 genes among the cell models. In addition, we observed that the in vitro model which most closely mimicked in vivo mRNA phenotype varied with both the gene and the patient. These results provide evidence that mRNA expression databases based on cancer cell lines, which are studied to provide a rationale for selection of therapy on the basis of molecular characteristics of a patient's tumour, must be carefully interpreted. British Journal of Cancer (2002) 86, 1283–1289. DOI: 10.1038/sj/bjc/6600239 www.bjcancer.com © 2002 Cancer Research UK PMID:11953886

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

    PubMed Central

    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

    2016-01-01

    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. PMID:26716509

  14. 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

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

    PubMed Central

    2013-01-01

    Background Stage shift is widely considered a major determinant of the survival benefit conferred by breast cancer screening. However, factors and mechanisms underlying such a prognostic advantage need further clarification. We sought to compare the molecular characteristics of screen detected vs. symptomatic breast cancers and assess whether differences in tumour biology might translate into survival benefit. Methods In a clinical series of 448 women with operable breast cancer, the Kaplan-Meier method and the log-rank test were used to estimate the likelihood of cancer recurrence and death. The Cox proportional hazard model was used for the multivariate analyses including mode of detection, age at diagnosis, tumour size, and lymph node status. These same models were applied to subgroups defined by molecular subtypes. Results Screen detected breast cancers tended to show more favourable clinicopathological features and survival outcomes compared to symptomatic cancers. The luminal A subtype was more common in women with mammography detected tumours than in symptomatic patients (68.5 vs. 59.0%, p=0.04). Data analysis across categories of molecular subtypes revealed significantly longer disease free and overall survival for screen detected cancers with a luminal A subtype only (p=0.01 and 0.02, respectively). For women with a luminal A subtype, the independent prognostic role of mode of detection on recurrence was confirmed in Cox proportional hazard models (p=0.03). An independent role of modality of detection on survival was also suggested (p=0.05). Conclusions Molecular subtypes did not substantially explain the differences in survival outcomes between screened and symptomatic patients. However, our results suggest that molecular profiles might play a role in interpreting such differences at least partially. Further studies are warranted to reinterpret the efficacy of screening programmes in the light of tumour biology. PMID:23305429

  16. Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling

    PubMed Central

    Pan, Sheng; Chen, Ru; Crispin, David A.; May, Damon; Stevens, Tyler; McIntosh, Martin; Bronner, Mary P.; Ziogas, Argyrios; Anton-Culver, Hoda; Brentnall, Teresa A.

    2011-01-01

    Pancreatic cancer is a lethal disease that is difficult to diagnose at early stages when curable treatments are effective. Biomarkers that can improve current pancreatic cancer detection would have great value in improving patient management and survival rate. A large scale quantitative proteomics study was performed to search for the plasma protein alterations associated with pancreatic cancer. The enormous complexity of the plasma proteome and the vast dynamic range of protein concentration therein present major challenges for quantitative global profiling of plasma. To address these challenges, multi-dimensional fractionation at both protein and peptide levels was applied to enhance the depth of proteomics analysis. Employing stringent criteria, more than thirteen hundred proteins total were identified in plasma across 8-orders of magnitude in protein concentration. Differential proteins associated with pancreatic cancer were identified, and their relationship with the proteome of pancreatic tissue and pancreatic juice from our previous studies was discussed. A subgroup of differentially expressed proteins was selected for biomarker testing using an independent cohort of plasma and serum samples from well-diagnosed patients with pancreatic cancer, chronic pancreatitis and non-pancreatic disease controls. Using ELISA methodology, the performance of each of these protein candidates was benchmarked against CA19-9, the current gold standard for a pancreatic cancer blood test. A composite marker of TIMP1 and ICAM1 demonstrate significantly better performance than CA19-9 in distinguishing pancreatic cancer from the non-pancreatic disease controls and chronic pancreatitis controls. In addition, protein AZGP1 was identified as a biomarker candidate for chronic pancreatitis. The discovery and technical challenges associated with plasma-based quantitative proteomics are discussed and may benefit the development of plasma proteomics technology in general. The protein

  17. Cancer

    MedlinePlus

    ... Leukemia Liver cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer ... have any symptoms. In certain cancers, such as pancreatic cancer, symptoms often do not start until the disease ...

  18. 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

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

    PubMed

    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

  20. Papillary Renal Carcinoma Presenting as a Cancer of Unknown Primary (CUP) and Diagnosed through Gene Expression Profiling

    PubMed Central

    Sorscher, Steven M.; Greco, Frank Anthony

    2012-01-01

    Cancer of unknown primary (CUP) is a clinical syndrome representing many types of cancers and diagnoses are typically made after review of clinical presentation, pathology (including immunohistochemical staining) and imaging studies. Treatment with systemic chemotherapy has been shown to result in fairly reproducible objective response rates. Herein, a case of a patient who was initially diagnosed with a poorly differentiated adenocarcinoma of unknown origin is reported. After mRNA gene expression profiling (commercially available CancerTYPE ID), a specific diagnosis of papillary renal cell carcinoma (RCC) was made and then confirmed with additional immunohistochemical staining. The patient was treated with targeted therapy and an objective radiographic response was seen. A literature review suggests this to be the first patient with papillary RCC, identified by molecular profiling, and benefitting from a targeted agent that otherwise would not have been considered in the setting of CUP. This case underscores the importance of considering the use of newer testing technologies in the interest of offering patients more specific, targeted therapy in order to improve efficacy and spare patients toxicities of less specific, empiric chemotherapeutic regimens. PMID:22679428

  1. The prostate cancer immunome: In silico functional analysis of antigenic proteins from microarray profiling with IgG.

    PubMed

    Luna-Coronell, Johana A; Vierlinger, Klemens; Gamperl, Magdalena; Hofbauer, Johann; Berger, Ingrid; Weinhäusel, Andreas

    2016-04-01

    The study of the immunome of prostate cancer (PCa) and characterization of autoantibody signature from differentially reactive antigens can uncover disease stage proteins, reveal enriched networks and even expose aberrant cellular mechanisms during the disease process. By conducting plasma IgG profiling on protein microarrays presenting 5449 unique human proteins expressed in 15 417 E. coli human cDNA expression clones, we elucidated 471 (21 higher reactive in PCa) differentially reactive antigens in 50 PCa versus 49 patients with benign prostate hyperplasia (BPH) at initial diagnosis. Functional analyzes show that the immune-profile of PCa compared to BPH control samples is significantly enriched in features targeting Cellular assembly, Cell death and pathways involved in Cell cycle, translation, and assembly of proteins as EIF2 signaling, PCa related genes as AXIN1 and TP53, and ribosomal proteins (e.g. RPS10). An overlap of 61 (out of 471) DIRAGs with the published 1545 antigens from the SEREX database has been found, however those were higher reactive in BPH. Clinical relevance is shown when antibody-reactivities against eight proteins were significantly (p < 0.001) correlated with Gleason-score. Herewith we provide a biological and pathophysiological characterization of the immunological layer of cancerous (PCa) versus benign (BPH) disease, derived from antibody profiling on protein microarrays. PMID:27089054

  2. Clinical utility of gene-expression profiling in women with early breast cancer: an overview of systematic reviews

    PubMed Central

    Marrone, Michael; Stewart, Alison; Dotson, W. David

    2015-01-01

    Purpose This overview systematically evaluates the clinical utility of using Oncotype DX and MammaPrint gene-expression profiling tests to direct treatment decisions in women with breast cancer. The findings are intended to inform an updated recommendation from the Evaluation of Genomic Applications in Practice and Prevention Working Group. Methods Evidence reported in systematic reviews evaluating the clinical utility of Oncotype DX and MammaPrint, as well as the ability to predict treatment outcomes, change in treatment decisions, and cost-effectiveness, was qualitatively synthesized. Results Five systematic reviews found no direct evidence of clinical utility for either test. Indirect evidence showed Oncotype DX was able to predict treatment effects of adjuvant chemotherapy, whereas no evidence of predictive value was found for MammaPrint. Both tests influenced a change in treatment recommendations in 21 to 74% of participants. The cost-effectiveness of Oncotype DX varied with the alternative compared. For MammaPrint, lack of evidence of the predictive value led to uncertainty in the cost-effectiveness. Conclusion No studies were identified that provided direct evidence that using gene-expression profiling tests to direct treatment decisions improved outcomes in women with breast cancer. Three ongoing studies may provide direct evidence for determining the clinical utility of gene-expression profiling testing. PMID:25474343

  3. Optical-mechanical signatures of cancer cells based on fluctuation profiles measured by interferometry.

    PubMed

    Bishitz, Yael; Gabai, Haniel; Girshovitz, Pinhas; Shaked, Natan T

    2014-08-01

    We propose to establish a cancer biomarker based on the unique optical-mechanical signatures of cancer cells measured in a noncontact, label-free manner by optical interferometry. Using wide-field interferometric phase microscopy (IPM), implemented by a portable, off-axis, common-path and low-coherence interferometric module, we quantitatively measured the time-dependent, nanometer-scale optical thickness fluctuation maps of live cells in vitro. We found that cancer cells fluctuate significantly more than healthy cells, and that metastatic cancer cells fluctuate significantly more than primary cancer cells. Atomic force microscopy (AFM) measurements validated the results. Our study shows the potential of IPM as a simple clinical tool for aiding in diagnosis and monitoring of cancer. PMID:23585163

  4. Profile of bevacizumab and its potential in the treatment of cervical cancer

    PubMed Central

    Fisher, Christine M; Schefter, Tracey E

    2015-01-01

    Blocking angiogenesis is an effective antitumor strategy proven in many disease sites. Anti-angiogenic therapies are fulfilling the promise of improved outcomes in cervical cancer as demonstrated in several recent trials. With its overall survival improvement in metastatic or recurrent cervical cancer, a frame shift in the management of these patients has occurred. The US Food and Drug Administration approval of bevacizumab in advanced cervical cancer has led to national guidelines, including the US National Comprehensive Cancer Network guidelines for cervical cancer, including systemic regimens containing bevacizumab as first line combination therapy. Future trials will build on this anti-angiogenesis backbone via targeting additional novel pathways and potentially leading to further improved outcomes in cervical cancer. PMID:26640382

  5. Profile of vintafolide (EC145) and its use in the treatment of platinum-resistant ovarian cancer

    PubMed Central

    Luyckx, Mathieu; Votino, Raffaella; Squifflet, Jean-Luc; Baurain, Jean-François

    2014-01-01

    Objective Our aim was to review the profile of vintafolide (EC145) and its rationale for use in platinum-resistant ovarian cancer. First we investigated the folate receptors (FRs), folate’s pathway into cells, and its expression in normal and cancerous cells, before detailing the mechanism of action of vintafolide, its clinical applications, and the results of different study phases. Materials and methods A literature search was conducted through PubMed/Medline, Google, ClinicalTrials.gov and websites of pharmaceutical companies. Only articles in English were selected. All articles investigating folate receptor expression in ovarian cancer were selected first, than articles reviewing platinum resistance. Papers about vintafolide were collected, while those talking about synthesis and biochemistry concerns were excluded. The different Phase I and II studies were read, and an update on the website of pharmaceuticals companies were added. Results FR is a bundle-membrane receptor that is expressed normally in some normal tissues on the apical surface of cells, but highly expressed in ovarian cancer cells (>80%). It collects folate through endocytosis. Chemotherapy does not modify its expression in ovarian cancer cells, and its expression appears to be mostly associated with a poor prognosis and platinum resistance. Vintafolide is a folate-desacetylvinblastine monohydrazide conjugate, allowing a liberation of the drug into the cytoplasm of cancerous cells via the FR-α (FRα) and endocytosis, with high specificity. Phase I studies showed a 2.5 mg bolus dose to be nontoxic, with moderately adverse events. Phase II clinical trials for the first time demonstrated a statistically significant improvement in disease-free survival in patients with platinum-resistant ovarian cancer, and in those with a very poor prognosis who had already received three to four lines of systemic chemotherapy. The greater benefits were observed in patients with highly expressed FRα. Conclusion

  6. Genomic Profiling Guides the Choice of Molecular Targeted Therapy of Pancreatic Cancer

    PubMed Central

    Frank, Thomas S.; Sun, Xiaotian; Zhang, Yuqing; Yang, Jingxuan; Fisher, William E.; Gingras, Marie-Claude; Li, Min

    2015-01-01

    Pancreatic cancer has the worst five-year survival rate of all malignancies due to its aggressive progression and resistance to therapy. Current therapies are limited to gemcitabine-based chemotherapeutics, surgery, and radiation. The current trend toward “personalized genomic medicine” has the potential to improve the treatment options for pancreatic cancer. Gene identification and genetic alterations like single nucleotide polymorphisms and mutations will allow physicians to predict the efficacy and toxicity of drugs, which could help diagnose pancreatic cancer, guide neoadjuvant or adjuvant treatment, and evaluate patients’ prognosis. This article reviews the multifaceted roles of genomics and pharmacogenomics in pancreatic cancer. PMID:25890222

  7. Gene expression profiling revealed novel mechanism of action of Taxotere and Furtulon in prostate cancer cells

    PubMed Central

    Li, Yiwei; Hussain, Maha; Sarkar, Sarah H; Eliason, James; Li, Ran; Sarkar, Fazlul H

    2005-01-01

    Background Both Taxotere and Capecitabine have shown anti-cancer activity against various cancers including prostate cancer. In combination, Taxotere plus Capecitabine has demonstrated higher anti-cancer activity in advanced breast cancers. However, the molecular mechanisms of action of Taxotere and Capecitabine have not been fully elucidated in prostate cancer. Methods The total RNA from PC3 and LNCaP prostate cells untreated and treated with 2 nM Taxotere, 110 μM Furtulon (active metabolite of Capecitabine), or 1 nM Taxotere plus 50 μM Furtulon for 6, 36, and 72 hours, was subjected to Affymetrix Human Genome U133A Array analysis. Real-time PCR and Western Blot analysis were conducted to confirm microarray data. Results Taxotere and Furtulon down-regulated some genes critical for cell proliferation, cell cycle progression, transcription factor, cell signaling, and oncogenesis, and up-regulated some genes related to the induction of apoptosis, cell cycle arrest, and differentiation in both cell lines. Taxotere and Furtulon also up-regulated some genes responsible for chemotherapeutic resistance, suggesting the induction of cancer cell resistance to these agents. Conclusions Taxotere and Furtulon caused the alternation of a large number of genes, many of which may contribute to the molecular mechanisms by which Taxotere and Furtulon inhibit the growth of prostate cancer cells. This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against prostate cancer. PMID:15656911

  8. Breakpoint Analysis of Transcriptional and Genomic Profiles Uncovers Novel Gene Fusions Spanning Multiple Human Cancer Types

    PubMed Central

    Giacomini, Craig P.; Sun, Steven; Varma, Sushama; Shain, A. Hunter; Giacomini, Marilyn M.; Balagtas, Jay; Sweeney, Robert T.; Lai, Everett; Del Vecchio, Catherine A.; Forster, Andrew D.; Clarke, Nicole; Montgomery, Kelli D.; Zhu, Shirley; Wong, Albert J.; van de Rijn, Matt; West, Robert B.; Pollack, Jonathan R.

    2013-01-01

    Gene fusions, like BCR/ABL1 in chronic myelogenous leukemia, have long been recognized in hematologic and mesenchymal malignancies. The recent finding of gene fusions in prostate and lung cancers has motivated the search for pathogenic gene fusions in other malignancies. Here, we developed a “breakpoint analysis” pipeline to discover candidate gene fusions by tell-tale transcript level or genomic DNA copy number transitions occurring within genes. Mining data from 974 diverse cancer samples, we identified 198 candidate fusions involving annotated cancer genes. From these, we validated and further characterized novel gene fusions involving ROS1 tyrosine kinase in angiosarcoma (CEP85L/ROS1), SLC1A2 glutamate transporter in colon cancer (APIP/SLC1A2), RAF1 kinase in pancreatic cancer (ATG7/RAF1) and anaplastic astrocytoma (BCL6/RAF1), EWSR1 in melanoma (EWSR1/CREM), CDK6 kinase in T-cell acute lymphoblastic leukemia (FAM133B/CDK6), and CLTC in breast cancer (CLTC/VMP1). Notably, while these fusions involved known cancer genes, all occurred with novel fusion partners and in previously unreported cancer types. Moreover, several constituted druggable targets (including kinases), with therapeutic implications for their respective malignancies. Lastly, breakpoint analysis identified new cell line models for known rearrangements, including EGFRvIII and FIP1L1/PDGFRA. Taken together, we provide a robust approach for gene fusion discovery, and our results highlight a more widespread role of fusion genes in cancer pathogenesis. PMID:23637631

  9. 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

  10. 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

  11. 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

  12. Home Care

    MedlinePlus

    ... Help Related Topics Assisted Living Community-Based Care Nursing Homes Related Video Join our e-newsletter! Aging & Health A to Z Home Care Basic Facts & Information Role of Health Care Professionals in Home Care Your physician is the leader ...

  13. How to Check Your Skin for Skin Cancer

    MedlinePlus

    ... Home Cancer Types Skin Cancer Skin Cancer Patient Skin Cancer Treatment Melanoma Treatment Merkel Cell Carcinoma Treatment Skin Cancer Prevention Skin Cancer Screening Health Professional Skin Cancer Treatment Melanoma Treatment Merkel Cell Carcinoma Treatment Skin Cancer ...

  14. The Development of an Angiogenic Protein "Signature" in Ovarian Cancer Ascites as a Tool for Biologic and Prognostic Profiling.

    PubMed

    Trachana, Sofia-Paraskevi; Pilalis, Eleftherios; Gavalas, Nikos G; Tzannis, Kimon; Papadodima, Olga; Liontos, Michalis; Rodolakis, Alexandros; Vlachos, Georgios; Thomakos, Nikolaos; Haidopoulos, Dimitrios; Lykka, Maria; Koutsoukos, Konstantinos; Kostouros, Efthimios; Terpos, Evagelos; Chatziioannou, Aristotelis; Dimopoulos, Meletios-Athanasios; Bamias, Aristotelis

    2016-01-01

    Advanced ovarian cancer (AOC) is one of the leading lethal gynecological cancers in developed countries. Based on the important role of angiogenesis in ovarian cancer oncogenesis and expansion, we hypothesized that the development of an "angiogenic signature" might be helpful in prediction of prognosis and efficacy of anti-angiogenic therapies in this disease. Sixty-nine samples of ascitic fluid- 35 from platinum sensitive and 34 from platinum resistant patients managed with cytoreductive surgery and 1st-line carboplatin-based chemotherapy- were analyzed using the Proteome ProfilerTM Human Angiogenesis Array Kit, screening for the presence of 55 soluble angiogenesis-related factors. A protein profile based on the expression of a subset of 25 factors could accurately separate resistant from sensitive patients with a success rate of approximately 90%. The protein profile corresponding to the "sensitive" subset was associated with significantly longer PFS (8 [95% Confidence Interval {CI}: 8-9] vs. 20 months [95% CI: 15-28]; Hazard ratio {HR}: 8.3, p<0.001) and OS (20.5 months [95% CI: 13.5-30] vs. 74 months [95% CI: 36-not reached]; HR: 5.6 [95% CI: 2.8-11.2]; p<0.001). This prognostic performance was superior to that of stage, histology and residual disease after cytoreductive surgery and the levels of vascular endothelial growth factor (VEGF) in ascites. In conclusion, we developed an "angiogenic signature" for patients with AOC, which can be used, after appropriate validation, as a prognostic marker and a tool for selection for anti-angiogenic therapies. PMID:27258020

  15. Assessing early therapeutic response to bevacizumab in primary breast cancer using magnetic resonance imaging and gene expression profiles.

    PubMed

    Mehta, Shaveta; Hughes, Nicholas P; Buffa, Francesca M; Li, Sonia P; Adams, Rosemary F; Adwani, Asha; Taylor, N Jane; Levitt, Nicola C; Padhani, Anwar R; Makris, Andreas; Harris, Adrian L

    2011-01-01

    Antiangiogenic therapy is a promising approach for the treatment of breast cancer. In practice, however, only a subset of patients who receive antiangiogenic drugs demonstrate a significant response. A key challenge, therefore, is to discover biomarkers that are predictive of response to antiangiogenic therapy. To address this issue, we have designed a window-of-opportunity study in which bevacizumab is administered as a short-term first-line treatment to primary breast cancer patients. Central to our approach is the use of a detailed pharmacodynamic assessment, consisting of pre- and post-bevacizumab multi-parametric magnetic resonance imaging scans and core biopsies for exon array gene expression analysis. Here, we illustrate three intrinsic patterns of response to bevacizumab and discuss the molecular mechanisms that may underpin each. Our results illustrate how the combination of dynamic imaging data and gene expression profiles can guide the development of biomarkers for predicting response to antiangiogenic therapy. PMID:22043045

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

    PubMed Central

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

    2015-01-01

    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. PMID:25970776

  17. 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. PMID:21104502

  18. A novel subtype classification and risk of breast cancer by histone modification profiling.

    PubMed

    Chen, Xiaohua; Hu, Hanyang; He, Lin; Yu, Xueyuan; Liu, Xiangyu; Zhong, Rong; Shu, Maoguo

    2016-06-01

    Breast cancer has been classified into several intrinsic molecular subtypes on the basis of genetic and epigenetic factors. However, knowledge about histone modifications that contribute to the classification and development of biologically distinct breast cancer subtypes remains limited. Here we compared the genome-wide binding patterns of H3K4me3 and H3K27me3 between human mammary epithelial cells and three breast cancer cell lines representing the luminal, HER2, and basal subtypes. We characterized thousands of unique binding events as well as bivalent chromatin signatures unique to each cancer subtype, which were involved in different epigenetic regulation programs and signaling pathways in breast cancer progression. Genes linked to the unique histone mark features exhibited subtype-specific expression patterns, both in cancer cell lines and primary tumors, some of which were confirmed by qPCR in our primary cancer samples. Finally, histone mark-based gene classifiers were significantly correlated with relapse-free survival outcomes in patients. In summary, we have provided a valuable resource for the identification of novel biomarkers of subtype classification and clinical prognosis evaluation in breast cancers. PMID:27178334

  19. 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…

  20. Blood Genome-Wide Transcriptional Profiles of HER2 Negative Breast Cancers Patients

    PubMed Central

    Balacescu, Ovidiu; Balacescu, Loredana; Gherman, Claudia; Drigla, Flaviu; Pop, Laura; Bolba-Morar, Gabriela; Tudoran, Oana; Berindan-Neagoe, Ioana

    2016-01-01

    Tumors act systemically to sustain cancer progression, affecting the physiological processes in the host and triggering responses in the blood circulating cells. In this study, we explored blood transcriptional patterns of patients with two subtypes of HER2 negative breast cancers, with different prognosis and therapeutic outcome. Peripheral blood samples from seven healthy female donors and 29 women with breast cancer including 14 triple-negative breast cancers and 15 hormone-dependent breast cancers were evaluated by microarray. We also evaluated the stroma in primary tumors. Transcriptional analysis revealed distinct molecular signatures in the blood of HER2− breast cancer patients according to ER/PR status. Our data showed the implication of immune signaling in both breast cancer subtypes with an enrichment of these processes in the blood of TNBC patients. We observed a significant alteration of “chemokine signaling,” “IL-8 signaling,” and “communication between innate and adaptive immune cells” pathways in the blood of TNBC patients correlated with an increased inflammation and necrosis in their primary tumors. Overall, our data indicate that the presence of triple-negative breast cancer is associated with an enrichment of altered systemic immune-related pathways, suggesting that immunotherapy could possibly be synergistic to the chemotherapy, to improve the clinical outcome of these patients. PMID:26884644

  1. 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.

  2. Genomic and Proteomic Profiles Reveal the Association of Gelsolin to TP53 Status and Bladder Cancer Progression

    PubMed Central

    Sanchez-Carbayo, Marta; Socci, Nicholas D.; Richstone, Lee; Corton, Marta; Behrendt, Nille; Wulkfuhle, Julia; Bochner, Bernard; Petricoin, Emmanuel; Cordon-Cardo, Carlos

    2007-01-01

    Bladder cancer transformation and immortalization require the inactivation of key regulatory genes, including TP53. Genotyping of a large cohort of bladder cancer patients (n = 256) using the TP53 GeneChip showed mutations in 103 cases (40.2%), the majority of them mapping to the DNA-binding core domain. TP53 mutation status was significantly associated with tumor stage (P = 0.0001) and overall survival for patients with advanced disease (P = 0.01). Transcript profiling using oligonucleotide arrays was performed on a subset of these cases (n = 46). Supervised analyses identified genes differentially expressed between invasive bladder tumors with wild-type (n = 24) and mutated TP53 (n = 22). Pathway analyses of top-ranked genes supported the central role of TP53 in the functional network of such gene patterns. A proteomic strategy using reverse phase arrays with protein extracts of bladder cancer cell lines validated the association of identified differentially expressed genes, such as gelsolin, to TP53 status. Immunohistochemistry on tissue microarrays (n = 294) revealed that gelsolin was associated with tumor stage and overall survival, correlating positively with TP53 status in a subset of these patients. This study further reveals that TP53 mutations are frequent events in bladder cancer progression and identified gelsolin related to TP53 status, tumor staging, and clinical outcome by independent high-throughput strategies. PMID:17982131

  3. Patient-specific driver gene prediction and risk assessment through integrated network analysis of cancer omics profiles.

    PubMed

    Bertrand, Denis; Chng, Kern Rei; Sherbaf, Faranak Ghazi; Kiesel, Anja; Chia, Burton K H; Sia, Yee Yen; Huang, Sharon K; Hoon, Dave S B; Liu, Edison T; Hillmer, Axel; Nagarajan, Niranjan

    2015-04-20

    Extensive and multi-dimensional data sets generated from recent cancer omics profiling projects have presented new challenges and opportunities for unraveling the complexity of cancer genome landscapes. In particular, distinguishing the unique complement of genes that drive tumorigenesis in each patient from a sea of passenger mutations is necessary for translating the full benefit of cancer genome sequencing into the clinic. We address this need by presenting a data integration framework (OncoIMPACT) to nominate patient-specific driver genes based on their phenotypic impact. Extensive in silico and in vitro validation helped establish OncoIMPACT's robustness, improved precision over competing approaches and verifiable patient and cell line specific predictions (2/2 and 6/7 true positives and negatives, respectively). In particular, we computationally predicted and experimentally validated the gene TRIM24 as a putative novel amplified driver in a melanoma patient. Applying OncoIMPACT to more than 1000 tumor samples, we generated patient-specific driver gene lists in five different cancer types to identify modes of synergistic action. We also provide the first demonstration that computationally derived driver mutation signatures can be overall superior to single gene and gene expression based signatures in enabling patient stratification and prognostication. Source code and executables for OncoIMPACT are freely available from http://sourceforge.net/projects/oncoimpact. PMID:25572314

  4. Transcriptome profiling identifies genes and pathways deregulated upon floxuridine treatment in colorectal cancer cells harboring GOF mutant p53.

    PubMed

    Datta, Arindam; Dey, Sanjib; Das, Pijush; Alam, Sk Kayum; Roychoudhury, Susanta

    2016-06-01

    Mutation in TP53 is a common genetic alteration in human cancers. Certain tumor associated p53 missense mutants acquire gain-of-function (GOF) properties and confer oncogenic phenotypes including enhanced chemoresistance. The colorectal cancers (CRC) harboring mutant p53 are generally aggressive in nature and difficult to treat. To identify a potential gene expression signature of GOF mutant p53-driven acquired chemoresistance in CRC, we performed transcriptome profiling of floxuridine (FUdR) treated SW480 cells expressing mutant p53(R273H) (GEO#: GSE77533). We obtained several genes differentially regulated between FUdR treated and untreated cells. Further, functional characterization and pathway analysis revealed significant enrichment of crucial biological processes and pathways upon FUdR treatment in SW480 cells. Our data suggest that in response to chemotherapeutics treatment, cancer cells with GOF mutant p53 can modulate key cellular pathways to withstand the cytotoxic effect of the drugs. The genes and pathways identified in the present study can be further validated and targeted for better chemotherapy response in colorectal cancer patients harboring mutant p53. PMID:27114909

  5. 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

  6. 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

  7. 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.

  8. Large-scale profiling of microRNAs for The Cancer Genome Atlas

    PubMed Central

    Chu, Andy; Robertson, Gordon; Brooks, Denise; Mungall, Andrew J.; Birol, Inanc; Coope, Robin; Ma, Yussanne; Jones, Steven; Marra, Marco A.

    2016-01-01

    The comprehensive multiplatform genomics data generated by The Cancer Genome Atlas (TCGA) Research Network is an enabling resource for cancer research. It includes an unprecedented amount of microRNA sequence data: ∼11 000 libraries across 33 cancer types. Combined with initiatives like the National Cancer Institute Genomics Cloud Pilots, such data resources will make intensive analysis of large-scale cancer genomics data widely accessible. To support such initiatives, and to enable comparison of TCGA microRNA data to data from other projects, we describe the process that we developed and used to generate the microRNA sequence data, from library construction through to submission of data to repositories. In the context of this process, we describe the computational pipeline that we used to characterize microRNA expression across large patient cohorts. PMID:26271990

  9. 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.

  10. 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

  11. Large-scale profiling of microRNAs for The Cancer Genome Atlas.

    PubMed

    Chu, Andy; Robertson, Gordon; Brooks, Denise; Mungall, Andrew J; Birol, Inanc; Coope, Robin; Ma, Yussanne; Jones, Steven; Marra, Marco A

    2016-01-01

    The comprehensive multiplatform genomics data generated by The Cancer Genome Atlas (TCGA) Research Network is an enabling resource for cancer research. It includes an unprecedented amount of microRNA sequence data: ~11 000 libraries across 33 cancer types. Combined with initiatives like the National Cancer Institute Genomics Cloud Pilots, such data resources will make intensive analysis of large-scale cancer genomics data widely accessible. To support such initiatives, and to enable comparison of TCGA microRNA data to data from other projects, we describe the process that we developed and used to generate the microRNA sequence data, from library construction through to submission of data to repositories. In the context of this process, we describe the computational pipeline that we used to characterize microRNA expression across large patient cohorts. PMID:26271990

  12. Histopathological, Molecular, and Genetic Profile of Hereditary Diffuse Gastric Cancer: Current Knowledge and Challenges for the Future.

    PubMed

    van der Post, Rachel S; Gullo, Irene; Oliveira, Carla; Tang, Laura H; Grabsch, Heike I; O'Donovan, Maria; Fitzgerald, Rebecca C; van Krieken, Han; Carneiro, Fátima

    2016-01-01

    Familial clustering is seen in 10 % of gastric cancer cases and approximately 1-3 % of gastric cancer arises in the setting of hereditary diffuse gastric cancer (HDGC). In families with HDGC, gastric cancer presents at young age. HDGC is predominantly caused by germline mutations in CDH1 and in a minority by mutations in other genes, including CTNNA1. Early stage HDGC is characterized by a few, up to dozens of intramucosal foci of signet ring cell carcinoma and its precursor lesions. These include in situ signet ring cell carcinoma and pagetoid spread of signet ring cells. Advanced HDGC presents as poorly cohesive/diffuse type carcinoma, normally with very few typical signet ring cells, and has a poor prognosis. Currently, it is unknown which factors drive the progression towards aggressive disease, but it is clear that most intramucosal lesions will not have such progression.Immunohistochemical profile of early and advanced HDGC is often characterized by abnormal E-cadherin immunoexpression, including absent or reduced membranous expression, as well as "dotted" or cytoplasmic expression. However, membranous expression of E-cadherin does not exclude HDGC. Intramucosal HDGC (pT1a) presents with an "indolent" phenotype, characterized by typical signet ring cells without immunoexpression of Ki-67 and p53, while advanced carcinomas (pT > 1) display an "aggressive" phenotype with pleomorphic cells, that are immunoreactive for Ki-67 and p53. These features show that the IHC profile is different between intramucosal and more advanced HDGC, providing evidence of phenotypic heterogeneity, and may help to define predictive biomarkers of progression from indolent to aggressive, widely invasive carcinomas. PMID:27573781

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

    PubMed

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

    2016-02-01

    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

  14. 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

  15. 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 ...

  16. Symptoms of Ovarian Cancer

    MedlinePlus

    ... Informed Cancer Home What Are the Symptoms of Ovarian Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Gynecologic cancer symptoms diaries Ovarian cancer may cause one or more of these signs ...

  17. 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 Print to PDF ...

  18. Geriatric study in Europe on health effects of air quality in nursing homes (GERIE study) profile: objectives, study protocol and descriptive data

    PubMed Central

    2013-01-01

    Background Indoor air pollution (IAP) constitutes a major global public health problem requiring increasing efforts in research and policymaking that may have special significance for elderly that are likely to spend most of their day indoors and appear to be particularly susceptible to adverse effects of chemical pollutants and bio-contaminants. Yet, evidence existing on the effects of IAP in elderly is scanty. The Geriatric study in Europe on health effects of air quality in nursing homes (GERIE) study aimed to assess health effects of major indoor air pollutants and thermal conditions in elderly (> 70 years) living stably in nursing homes (NH) across Europe. Respiratory effects were particularly considered as airways and lung constitute the first target of air pollutants. Objectives We describe here the rationale and the methods of the GERIE Study. Methods 8 nursing homes were randomly selected in 7 European countries. Twenty individuals were randomly selected in each nursing home. Major indoor and outdoor air chemical pollutants (PM10, PM2.5, PM0.1, formaldehyde, NO2; O3, VOC, CO2) and bio-contaminants (moulds, allergens) were assessed objectively with standardized procedures. Major health status indicators were assessed through a standardized questionnaire, non-invasive clinical tests and blood and urine biomarkers as well as saliva for ADN. Results The GERIE study has given the opportunity to publish two reviews on respiratory health effects of indoor and outdoor air pollution in elderly. In addition it has provided the inventory of air quality and thermal conditions in 50 nursing homes across Europe and data on respiratory health status in 600 elderly aged 82 years in mean. Major future results will include the relationships between NH environment and health in elderly. Conclusions The main long-term purpose of the GERIE study is to improve the health of elderly who permanently reside in nursing homes or of those who are exposed to indoor air pollution

  19. Profiling the expression pattern of GPI transamidase complex subunits in human cancer.

    PubMed

    Nagpal, Jatin K; Dasgupta, Santanu; Jadallah, Sana; Chae, Young K; Ratovitski, Edward A; Toubaji, Antoun; Netto, George J; Eagle, Toby; Nissan, Aviram; Sidransky, David; Trink, Barry

    2008-08-01

    The glycosylphosphatidylinositol transamidase complex (GPIT) consists of five subunits: PIG-U, PIG-T, GPAA1, PIG-S and GPI8, and is important in attaching GPI anchors to target proteins. On the basis of our previous reports incriminating PIG-U as an oncogene in bladder cancer and PIG-T and GPAA1 as oncogenes in breast cancer, we evaluated the expression pattern of the GPIT subunits in 19 different human cancers at both mRNA and protein levels. In general, our results demonstrate a more frequent expression of GPIT subunits in cancers than in normal. Among the 19 anatomic sites compared; breast, ovary and uterus showed consistent evidence of overexpression of specific GPIT subunits. There was also overexpression of PIG-U and GPI8 in lymphoma. In addition, non-small cell lung carcinoma showed significant overexpression of the GPIT subunits as compared to small cell lung carcinoma and normal lung tissue. Also, deregulation of specific GPIT subunits was seen in various other cancers. Forced overexpression of two GPIT subunits; PIG-S and GPI8 alone or in combination induced increased proliferation and invasion of breast cancer cells. Collectively, our study defines a trend involving the deregulated expression and the functional contribution of the GPIT subunits in various cancers with potential implications in diagnosis, prognosis and therapeutic intervention. PMID:18487995

  20. Quantitative profiling of colorectal cancer-associated bacteria reveals associations between fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer.

    PubMed

    Viljoen, Katie S; Dakshinamurthy, Amirtha; Goldberg, Paul; Blackburn, Jonathan M

    2015-01-01

    Various studies have presented clinical or in vitro evidence linking bacteria to colorectal cancer, but these bacteria have not previously been concurrently quantified by qPCR in a single cohort. We quantify these bacteria (Fusobacterium spp., Streptococcus gallolyticus, Enterococcus faecalis, Enterotoxigenic Bacteroides fragilis (ETBF), Enteropathogenic Escherichia coli (EPEC), and afaC- or pks-positive E. coli) in paired tumour and normal tissue samples from 55 colorectal cancer patients. We further investigate the relationship between a) the presence and b) the level of colonisation of each bacterial species with site and stage of disease, age, gender, ethnicity and MSI-status. With the exception of S. gallolyticus, we detected all bacteria profiled here in both tumour and normal samples at varying frequencies. ETBF (FDR = 0.001 and 0.002 for normal and tumour samples) and afaC-positive E. coli (FDR = 0.03, normal samples) were significantly enriched in the colon compared to the rectum. ETBF (FDR = 0.04 and 0.002 for normal and tumour samples, respectively) and Fusobacterium spp. (FDR = 0.03 tumour samples) levels were significantly higher in late stage (III/IV) colorectal cancers. Fusobacterium was by far the most common bacteria detected, occurring in 82% and 81% of paired tumour and normal samples. Fusobacterium was also the only bacterium that was significantly higher in tumour compared to normal samples (p = 6e-5). We also identified significant associations between high-level colonisation by Fusobacterium and MSI-H (FDR = 0.05), age (FDR = 0.03) or pks-positive E. coli (FDR = 0.01). Furthermore, we exclusively identified atypical EPEC in our cohort, which has not been previously reported in association with colorectal cancer. By quantifying colorectal cancer-associated bacteria across a single cohort, we uncovered inter- and intra-individual patterns of colonization not previously recognized, as well as important associations with clinicopathological

  1. Expression profile of innate immune receptors, NLRs and AIM2, in human colorectal cancer: correlation with cancer stages and inflammasome components

    PubMed Central

    Chen, Liang; Hu, Peizhen; Li, Zengshan; Chen, Jun; Song, Chaojun; Chen, Lihua; Ting, Jenny Pan-Yun

    2015-01-01

    NLRs (nucleotide-binding domain leucine-rich repeat proteins or NOD-like receptors) are regulators of inflammation and immunity. A subgroup of NLRs and the innate immune receptor, AIM2 (absent-in-melanoma 2), can induce the assembly of a large caspase-1 activating complex called the inflammasome. Other NLRs regulate key signaling pathways such as NF-kB and MAPK. Since inflammation is a central component of colorectal cancer (CRC), this work was undertaken to analyze NLR and AIM2 expression in human CRC by combining bioinformatics analysis and experimental verification using clinical tissue samples. Additional experiments analyzed the association of (i) gene expression and cancer staging, and (ii) gene expression among inflammasome components. Ten public CRC datasets from the Oncomine® Platform were analyzed. Genes analyzed include NLRP1, NLRP3, NLRP6, NLRP12, NLRC3, NLRC4, NLRC5, NOD1, NOD2 and AIM2. Additionally, forty case-matched cancer samples and adjacent healthy control tissues isolated from a cohort of Chinese CRC patients were profiled. Three patterns of gene expression in CRC are shown. The expression of NLRC3, a checkpoint of inflammation, and the inflammasome components NLRP1, NLRP3, NLRC4 and AIM2 were reduced in CRC. NOD1 and NOD2 expression was increased in CRC, while NLRC5, NLRP6 and NLRP12 showed little difference compared to controls. Reduced expression of NLRC3 in CRC was verified in all available databases analyzed and confirmed with our patient cohort. Furthermore, the extent of NLRC3 and AIM2 gene reduction was correlated with cancer progression. This report reveals the potential value of NLR and AIM2 genes as biomarkers of CRC and cancer progression. PMID:26378020

  2. Expression profile of innate immune receptors, NLRs and AIM2, in human colorectal cancer: correlation with cancer stages and inflammasome components.

    PubMed

    Liu, Rongrong; Truax, Agnieszka D; Chen, Liang; Hu, Peizhen; Li, Zengshan; Chen, Jun; Song, Chaojun; Chen, Lihua; Ting, Jenny Pan-Yun

    2015-10-20

    NLRs (nucleotide-binding domain leucine-rich repeat proteins or NOD-like receptors) are regulators of inflammation and immunity. A subgroup of NLRs and the innate immune receptor, AIM2 (absent-in-melanoma 2), can induce the assembly of a large caspase-1 activating complex called the inflammasome. Other NLRs regulate key signaling pathways such as NF-kB and MAPK. Since inflammation is a central component of colorectal cancer (CRC), this work was undertaken to analyze NLR and AIM2 expression in human CRC by combining bioinformatics analysis and experimental verification using clinical tissue samples. Additional experiments analyzed the association of (i) gene expression and cancer staging, and (ii) gene expression among inflammasome components.Ten public CRC datasets from the Oncomine® Platform were analyzed. Genes analyzed include NLRP1, NLRP3, NLRP6, NLRP12, NLRC3, NLRC4, NLRC5, NOD1, NOD2 and AIM2. Additionally, forty case-matched cancer samples and adjacent healthy control tissues isolated from a cohort of Chinese CRC patients were profiled.Three patterns of gene expression in CRC are shown. The expression of NLRC3, a checkpoint of inflammation, and the inflammasome components NLRP1, NLRP3, NLRC4 and AIM2 were reduced in CRC. NOD1 and NOD2 expression was increased in CRC, while NLRC5, NLRP6 and NLRP12 showed little difference compared to controls. Reduced expression of NLRC3 in CRC was verified in all available databases analyzed and confirmed with our patient cohort. Furthermore, the extent of NLRC3 and AIM2 gene reduction was correlated with cancer progression. This report reveals the potential value of NLR and AIM2 genes as biomarkers of CRC and cancer progression. PMID:26378020

  3. Proteomic Profiling of Serum-Derived Exosomes from Ethnically Diverse Prostate Cancer Patients

    PubMed Central

    Turay, David; Khan, Salma; Osterman, Carlos J. Diaz; Curtis, Matthew P.; Khaira, Balreet; Neidigh, Jonathan W.; Mirshahidi, Saied; Casiano, Carlos A.; Wall, Nathan R.

    2015-01-01

    Prostate cancer (PCa) remains the most frequently diagnosed male malignancy in Western countries and the second most common cause of male cancer death in the United States. The relatively elevated PCa incidence and mortality among African American men makes this cancer type a challenging health disparity disease. To increase the chance for successful trea tment, earlier detection and prediction of tumor aggress iveness will be important and need to be resolved. This study demonstrates that small membrane-bound vesicles shed from the tumor called exosomes contain ethnically and tumor-specific biomarkers, and could be exploited for their diagnostic and therapeutic potential. PMID:26536157

  4. Anti-heat shock protein autoantibody profiling in breast cancer using customized protein microarray.

    PubMed

    Shi, Liu; Gehin, Thomas; Chevolot, Yann; Souteyrand, Eliane; Mangé, Alain; Solassol, Jérôme; Laurenceau, Emmanuelle

    2016-02-01

    Heat shock proteins (HSPs) are over-expressed in a wide range of human cancers. It results in the stimulation of the immune system and consequently in elevated concentration of anti-HSP autoantibodies. Elevated anti-HSP autoantibodies were found in breast cancer patients, and they are associated with tumor metastasis. Therefore, screening these autoantibodies could be of diagnostic and prognostic values. Protein microarrays have already demonstrated their great potential as a diagnostic tool. However, protein diversity requires optimization of the microarray fabrication to achieve high sensitivity and specificity. In this study, seven HSPs were immobilized on six different surface chemistries. After evaluation and optimization with purified antibodies of the six surface chemistries, two surfaces were selected to detect anti-HSP autoantibodies in breast cancer sera. Multiplex detection of anti-HSP autoantibodies allowed discrimination of breast cancer patients (50) from healthy controls (26) with a sensitivity of 86% and a specificity of 100%. PMID:26715250

  5. Differential gene expression profiles of gastric cancer cells established from primary tumour and malignant ascites

    PubMed Central

    Sakakura, C; Hagiwara, A; Nakanishi, M; Shimomura, K; Takagi, T; Yasuoka, R; Fujita, Y; Abe, T; Ichikawa, Y; Takahashi, S; Ishikawa, T; Nishizuka, I; Morita, T; Shimada, H; Okazaki, Y; Hayashizaki, Y; Yamagishi, H

    2002-01-01

    Advanced gastric cancer is often accompanied by metastasis to the peritoneum, resulting in a high mortality rate. Mechanisms involved in gastric cancer metastasis have not been fully clarified because metastasis involves multiple steps and requires a combination of altered expressions of many different genes. Thus, independent analysis of any single gene would be insufficient to understand all of the aspects of gastric cancer peritoneal dissemination. In this study, we performed a global analysis of the differential gene expression of a gastric cancer cell line established from a primary main tumour (SNU-1) and of other cell lines established from the metastasis to the peritoneal cavity (SNU-5, SNU-16, SNU-620, KATO-III and GT3TKB). The application of a high-density cDNA microarray method made it possible to analyse the expression of approximately 21 168 genes. Our examinations of SNU-5, SNU-16, SNU-620, KATO-III and GT3TKB showed that 24 genes were up-regulated and 17 genes down-regulated besides expression sequence tags. The analysis revealed the following altered expression such as: (a) up-regulation of CD44 (cell adhesion), keratins 7, 8, and 14 (epitherial marker), aldehyde dehydrogenase (drug metabolism), CD9 and IP3 receptor type3 (signal transduction); (b) down-regulation of IL2 receptor γ, IL4-Stat (immune response), p27 (cell cycle) and integrin β4 (adhesion) in gastric cancer cells from malignant ascites. We then analysed eight gastric cancer cell lines with Northern blot and observed preferential up-regulation and down-regulation of these selected genes in cells prone to peritoneal dissemination. Reverse transcriptase–polymerase chain reaction confirmed that several genes selected by DNA microarray were also overexpressed in clinical samples of malignant ascites. It is therefore considered that these genes may be related to the peritoneal dissemination of gastric cancers. The results of this global gene expression analysis of gastric cancer cells

  6. Immunohistochemical detection of ERβ in breast cancer: towards more detailed receptor profiling?

    PubMed Central

    Skliris, G P; Carder, P J; Lansdown, M R J; Speirs, V

    2001-01-01

    Oestrogen receptor (ER) is used routinely to predict endocrine responsiveness in patients with breast cancer. A second ER, ERβ has been described but its significance remains undefined; most studies have described mRNA levels rather than protein expression. Here, we demonstrate for the first time, immunohistochemical detection of ERβ in archival breast tumours. © 2001 Cancer Research Campaignhttp://www.bjcancer.com PMID:11308260

  7. 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

  8. 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. PMID:21633842

  9. 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

  10. Transcriptional profiling analysis and functional prediction of long noncoding RNAs in cancer

    PubMed Central

    Zhang, Meiying; Luo, Jianjun; Liu, Lihui; Wu, Wei; Xiao, Tengfei; Chen, Xiaowei; Chen, Xiaomin; Zhang, Dongdong; Xing, Rui; Tong, Xin; Wu, Nan; Zhao, Jian; Lu, Youyong; Guo, Mingzhou; Chen, Runsheng

    2016-01-01

    Long noncoding RNAs (lncRNAs), which are noncoding RNAs (ncRNAs) with length more than 200 nucleotides (nt), have been demonstrated to be involved in various types of cancer. Consequently, it has been frequently discussed that lncRNAs with aberrant expression in cancer serve as potential diagnostic biomarkers and therapeutic targets. However, one major challenge of developing cancer biomarkers is tumor heterogeneity which means that tumor cells show different cellular morphology, metastatic potential as well as gene expression. In this study, a custom designed microarray platform covering both mRNAs and lncRNAs was applied to tumor tissues of gastric, colon, liver and lung. 316 and 157 differentially expressed (DE-) protein coding genes and lncRNAs common to these four types of cancer were identified respectively. Besides, the functional roles of common DE-lncRNAs were inferred based on their expression and genomic position correlation with mRNAs. Moreover, mRNAs and lncRNAs with tissue specificity were also identified, suggesting their particular roles with regard to specific biogenesis and functions of different organs. Based on the large-scale survey of mRNAs and lncRNAs in four types of cancer, this study may offer new biomarkers common or specific for various types of cancer. PMID:26812883

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

    PubMed

    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

  12. Detection and identification of heat shock protein 10 as a biomarker in colorectal cancer by protein profiling.

    PubMed

    Melle, Christian; Bogumil, Ralf; Ernst, Günther; Schimmel, Bettina; Bleul, Annett; von Eggeling, Ferdinand

    2006-04-01

    Although colorectal cancer is one of the best-characterized tumors with regard to the multistep progression, it remains one of the most frequent and deadly neoplasms. For a better understanding of the molecular mechanisms behind the process of tumorigenesis and tumor progression, changes in protein expression between microdissected normal and tumorous colonic epithelium were analyzed. Cryostat sections from colorectal tumors, adenoma tissue, and adjacent normal mucosa were laser-microdissected and analyzed using ProteinChip Arrays. The derived MS profiles exhibited numerous statistical differences. One peak showing significantly high expression in the tumor was purified by reverse-phase chromatography and SDS-PAGE. The protein band of interest was passively eluted from the gel and identified as heat shock protein 10 (HSP 10) by tryptic digestion, peptide mapping, and MS/MS analysis. This tumor marker was further characterized by immunohistochemistry. Analysis of HSP 10-positive tissue by ProteinChip technology confirmed the identity of this protein. This work demonstrates that biomarker in colorectal cancer can be detected, identified, and assessed by a proteomic approach comprising tissue microdissection, protein profiling, and immunological techniques. In our experience, histological defined microdissected tissue areas should be used to identify proteins that might be responsible for tumorigenesis. PMID:16502466

  13. Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker

    PubMed Central

    Rachidi, Saleh M.; Qin, Tingting; Sun, Shaoli; Zheng, W. Jim; Li, Zihai

    2013-01-01

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

  14. Increased tumor homing and tissue penetration of the filamentous plant viral nanoparticle Potato virus X

    PubMed Central

    Shukla, Sourabh; Ablack, Amber L.; Wen, Amy M.; Lee, Karin L.; Lewis, John D.; Steinmetz, Nicole F.

    2012-01-01

    Nanomaterials with elongated architectures have been shown to possess differential tumor homing properties compared to their spherical counterparts. Here, we investigate whether this phenomenon is mirrored by plant viral nanoparticles that are filamentous (Potato virus X) or spherical (Cowpea mosaic virus). Our studies demonstrate that Potato virus X (PVX) and Cowpea mosaic virus (CPMV) show distinct biodistribution profiles and differ in their tumor homing and penetration efficiency. Analogous to what is seen with inorganic nanomaterials, PVX shows enhanced tumor homing and tissue penetration. Human tumor xenografts exhibit higher uptake of PEGylated filamentous PVX compared to CPMV, particularly in the core of the tumor. This is supported by immunohistochemical analysis of the tumor sections, which indicates greater penetration and accumulation of PVX within the tumor tissues. The enhanced tumor homing and retention properties of PVX along with its higher payload carrying capacity makes it a potentially superior platform for applications in cancer drug delivery and imaging applications. PMID:22731633

  15. Plasma free amino acid profiling of esophageal cancer using high-performance liquid chromatography spectroscopy

    PubMed Central

    Ma, Hong; Hasim, Ayshamgul; Mamtimin, Batur; Kong, Bin; Zhang, Hai-Ping; Sheyhidin, Ilyar

    2014-01-01

    AIM: To perform plasma free amino acid (PFAA) profiling of esophageal squamous cell carcinoma (ESCC) patients at different pathological stages and healthy subjects. METHODS: Plasma samples from ESCC patients (n = 51) and healthy control adults (n = 60) were analyzed by high-performance liquid chromatography (HPLC). The ESCC patients included moderate/poorly-differentiation (n = 24), lymph node metastasis (n = 17) and clinical stage > Ib2 (n = 36). Partial least squares discriminant analysis was performed to demonstrate that the PFAA metabolic patterns enabled discrimination between ESCC patients and controls, and the Student t test was applied to assess significant differences in PFAA concentrations between the two groups. RESULTS: There were significant differences in the PFAA profiles between controls and ESCC patients. Compared with healthy controls, the levels of Asp, Glu, Gly, His, Thr, Tau, Ala, Met, Ile, Leu, and Phe were decreased in ESCC patients, but Cys was increased. There exists a strong correlation between PFAA profiles and clinicopathological characteristics in ESCC patients. The levels of many PFAAs (i.e., Glu, Asp, Ser, Gly, Tau, Ala, Tyr, Val, Ile, and Leu) were related to pathological grading, lymph node metastasis, and ESCC clinical stage. Very good discrimination between ESCC patients and control subjects was achieved by multivariate modeling of plasma profiles. CONCLUSION: HPLC-based plasma profiling analysis was shown to be an effective approach to differentiate between ESCC patients and controls. PFAA profiles may have potential value for screening or diagnosing ESCC. PMID:25024622

  16. Non-invasive urinary metabolomic profiling identifies diagnostic and prognostic markers in lung cancer

    PubMed Central

    Mathé, Ewy A.; Patterson, Andrew D.; Haznadar, Majda; Manna, Soumen K.; Krausz, Kristopher W.; Bowman, Elise D.; Shields, Peter G.; Idle, Jeffrey R.; Smith, Philip B.; Anami, Katsuhiro; Kazandjian, Dickran G.; Hatzakis, Emmanuel; Gonzalez, Frank J.; Harris, Curtis C.

    2014-01-01

    Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (<1500 Da) were measured in urine collected from 469 lung cancer patients and 536 population controls using unbiased liquid chromatography-mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time points and further validated in an independent sample set, which comprises 80 cases and 78 population controls, with similar demographic and clinical characteristics when compared to the training set. Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel molecule identified in this study, and N-acetylneuraminic acid (NANA), were each significantly (P <0.00001) elevated in non–small cell lung cancer (NSCLC) and associated with worse prognosis (hazard ratio (HR) =1.81 [P =0.0002], and 1.54 [P =0.025], respectively). Creatine riboside was the strongest classifier of lung cancer status in all and stage I–II cases, important for early detection, and also associated with worse prognosis in stage I–II lung cancer (HR =1.71, P =0.048). All measurements were highly reproducible with intraclass correlation coefficients ranging from 0.82 – 0.99. Both metabolites were significantly (P <0.03) enriched in tumor tissue compared to adjacent non-tumor tissue (N =48), thus revealing their direct association with tumor metabolism. Creatine riboside and NANA may be robust urinary clinical metabolomic markers that are elevated in tumor tissue and associated with early lung cancer diagnosis and worse prognosis. PMID:24736543

  17. Noninvasive urinary metabolomic profiling identifies diagnostic and prognostic markers in lung cancer.

    PubMed

    Mathé, Ewy A; Patterson, Andrew D; Haznadar, Majda; Manna, Soumen K; Krausz, Kristopher W; Bowman, Elise D; Shields, Peter G; Idle, Jeffrey R; Smith, Philip B; Anami, Katsuhiro; Kazandjian, Dickran G; Hatzakis, Emmanuel; Gonzalez, Frank J; Harris, Curtis C

    2014-06-15

    Lung cancer remains the most common cause of cancer deaths worldwide, yet there is currently a lack of diagnostic noninvasive biomarkers that could guide treatment decisions. Small molecules (<1,500 Da) were measured in urine collected from 469 patients with lung cancer and 536 population controls using unbiased liquid chromatography/mass spectrometry. Clinical putative diagnostic and prognostic biomarkers were validated by quantitation and normalized to creatinine levels at two different time points and further confirmed in an independent sample set, which comprises 80 cases and 78 population controls, with similar demographic and clinical characteristics when compared with the training set. Creatine riboside (IUPAC name: 2-{2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-oxolan-2-yl]-1-methylcarbamimidamido}acetic acid), a novel molecule identified in this study, and N-acetylneuraminic acid (NANA) were each significantly (P < 0.00001) elevated in non-small cell lung cancer and associated with worse prognosis [HR = 1.81 (P = 0.0002), and 1.54 (P = 0.025), respectively]. Creatine riboside was the strongest classifier of lung cancer status in all and stage I-II cases, important for early detection, and also associated with worse prognosis in stage I-II lung cancer (HR = 1.71, P = 0.048). All measurements were highly reproducible with intraclass correlation coefficients ranging from 0.82 to 0.99. Both metabolites were significantly (P < 0.03) enriched in tumor tissue compared with adjacent nontumor tissue (N = 48), thus revealing their direct association with tumor metabolism. Creatine riboside and NANA may be robust urinary clinical metabolomic markers that are elevated in tumor tissue and associated with early lung cancer diagnosis and worse prognosis. PMID:24736543

  18. Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling.

    PubMed

    Zeller, C; Dai, W; Steele, N L; Siddiq, A; Walley, A J; Wilhelm-Benartzi, C S M; Rizzo, S; van der Zee, A; Plumb, J A; Brown, R

    2012-10-18

    Multiple DNA methylation changes in the cancer methylome are associated with the acquisition of drug resistance; however it remains uncertain how many represent critical DNA methylation drivers of chemoresistance. Using isogenic, cisplatin-sensitive/resistant ovarian cancer cell lines and inducing resensitizaton with demethylating agents, we aimed to identify consistent methylation and expression changes associated with chemoresistance. Using genome-wide DNA methylation profiling across 27 578 CpG sites, we identified loci at 4092 genes becoming hypermethylated in chemoresistant A2780/cp70 compared with the parental-sensitive A2780 cell line. Hypermethylation at gene promoter regions is often associated with transcriptional silencing; however, expression of only 245 of these hypermethylated genes becomes downregulated in A2780/cp70 as measured by microarray expression profiling. Treatment of A2780/cp70 with the demethylating agent 2-deoxy-5'-azacytidine induces resensitization to cisplatin and re-expression of 41 of the downregulated genes. A total of 13/41 genes were consistently hypermethylated in further independent cisplatin-resistant A2780 cell derivatives. CpG sites at 9 of the 13 genes (ARHGDIB, ARMCX2, COL1A, FLNA, FLNC, MEST, MLH1, NTS and PSMB9) acquired methylation in ovarian tumours at relapse following chemotherapy or chemoresistant cell lines derived at the time of patient relapse. Furthermore, 5/13 genes (ARMCX2, COL1A1, MDK, MEST and MLH1) acquired methylation in drug-resistant ovarian cancer-sustaining (side population) cells. MLH1 has a direct role in conferring cisplatin sensitivity when reintroduced into cells in vitro. This combined genomics approach has identified further potential key drivers of chemoresistance whose expression is silenced by DNA methylation that should be further evaluated as clinical biomarkers of drug resistance. PMID:22249249

  19. Expression Profiling of Macrophages Reveals Multiple Populations with Distinct Biological Roles in an Immunocompetent Orthotopic Model of Lung Cancer.

    PubMed

    Poczobutt, Joanna M; De, Subhajyoti; Yadav, Vinod K; Nguyen, Teresa T; Li, Howard; Sippel, Trisha R; Weiser-Evans, Mary C M; Nemenoff, Raphael A

    2016-03-15

    Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and they alter their phenotype in response to local environmental cues. Whereas the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes has not been well studied, particularly in lung cancer. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multimarker flow cytometry, we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and expresses multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor and selectively expresses a panel of chemokine genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict outcomes in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and they suggest that distinct populations play specific roles in tumor progression. PMID:26873985

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

    PubMed

    Mahmoud, Ali M; Aboul-Soud, Mourad A M; Han, Junkyu; Al-Sheikh, Yazeed A; Al-Abd, Ahmed M; El-Shemy, Hany A

    2016-05-01

    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

  1. Personalized home-based interval exercise training may improve cardiorespiratory fitness in cancer patients preparing to undergo hematopoietic cell transplantation.

    PubMed

    Wood, W A; Phillips, B; Smith-Ryan, A E; Wilson, D; Deal, A M; Bailey, C; Meeneghan, M; Reeve, B B; Basch, E M; Bennett, A V; Shea, T C; Battaglini, C L

    2016-07-01

    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 before autologous (N=20) or allogeneic (N=20) HCT. Each session consisted of five, 3 min intervals of walking, jogging or cycling at 65-95% maximal heart rate (MHR) with 3 min of low-intensity exercise (<65% MHR) between intervals. Participants were asked to perform sessions at least three 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 min 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 3.7 ml/kg min (P=0.005) and the median 6MWD improvement was 34 m (P=0.006). Home-based IET can be performed before HCT and has the potential to improve cardiorespiratory fitness. PMID:26999467

  2. Comprehensive genomic profiling of inflammatory breast cancer cases reveals a high frequency of clinically relevant genomic alterations.

    PubMed

    Ross, Jeffrey S; Ali, Siraj M; Wang, Kai; Khaira, Depinder; Palma, Norma A; Chmielecki, Juliann; Palmer, Gary A; Morosini, Deborah; Elvin, Julia A; Fernandez, Sandra V; Miller, Vincent A; Stephens, Philip J; Cristofanilli, Massimo

    2015-11-01

    Inflammatory breast cancer (IBC) is a distinct clinicopathologic entity that carries a worse prognosis relative to non-IBC breast cancer even when matched for standard biomarkers (ER/PR/HER2). The objective of this study was to identify opportunities for benefit from targeted therapy, which are not currently identifiable in the standard workup for advanced breast cancer. Comprehensive genomic profiling on 53 IBC formalin-fixed paraffin-embedded specimens (mean, 800× + coverage) using the hybrid capture-based FoundationOne assay. Academic and community oncology clinics. From a series of 2208 clinical cases of advanced/refractory invasive breast cancers, 53 cases with IBC were identified. The presence of clinically relevant genomic alterations (CRGA) in IBC and responses to targeted therapies. CRGA were defined as genomic alterations (GA) associated with on label targeted therapies and targeted therapies in mechanism-driven clinical trials. For the 44 IBCs with available biomarker data, 19 (39 %) were ER-/PR-/HER2- (triple-negative breast cancer, TNBC). For patients in which the clinical HER2 status was known, 11 (25 %) were HER2+ with complete (100 %) concordance with ERBB2 (HER2) amplification detected by the CGP assay. The 53 sequenced IBC cases harbored a total of 266 GA with an average of 5.0 GA/tumor (range 1-15). At least one alteration associated with an FDA approved therapy or clinical trial was identified in 51/53 (96 %) of cases with an average of 2.6 CRGA/case. The most frequently altered genes were TP53 (62 %), MYC (32 %), PIK3CA (28 %), ERBB2 (26 %), FGFR1 (17 %), BRCA2 (15 %), and PTEN (15 %). In the TNBC subset of IBC, 8/19 (42 %) showed MYC amplification (median copy number 8X, range 7-20) as compared to 9/32 (28 %) in non-TNBC IBC (median copy number 7X, range 6-21). Comprehensive genomic profiling uncovered a high frequency of GA in IBC with 96 % of cases harboring at least 1 CRGA. The clinical benefit of selected targeted

  3. Tumoral profile in Down syndrome: A step towards the understanding of the consequences of aneuploidy and the development of cancer

    SciTech Connect

    Stage, D.; Sommelet, D.; Geneix, A.

    1994-09-01

    A review of the tumoral profile observed in Down syndrome has been done. Besides the well-known presence of congenital leukemia (recurring during childhood in 25% of cases) and the excess of acute leukemias occurring in the first two years of life where the nonlymphocytic (FAB M7) type is much more common than the lymphocytic (pre-B) type, some solid tumors are also observed more frequently in Down syndrome patients than in the general population. For example, one observes in Down syndrome patients an excess of lymphoma, germ cell tumors (testicular and extra testicular) as well as bone and pancreatic tumors. These tumors are often observed in male Down syndrome patients and occur sometimes during the fetal life. On the contrary, some tumors are less frequently observed in a Down syndrome population than in the general population. For example, in children, kidney and neurological (central and peripheral) tumors and in adults, digestive, pulmonary, skin, kidney, breast and uterine cancers are rare. These data suggest that there might be on chromosome 21, genes that may predispose or protect for cancer. The positioning of these genes by centromeric mapping in patients with trisomy 21 might be useful for the understanding of the consequences of aneuploidy and the development of cancer.

  4. A Comparison of DESI-MS and LC-MS for the Lipidomic Profiling of Human Cancer Tissue

    NASA Astrophysics Data System (ADS)

    Abbassi-Ghadi, Nima; Jones, Emrys A.; Gomez-Romero, Maria; Golf, Ottmar; Kumar, Sacheen; Huang, Juzheng; Kudo, Hiromi; Goldin, Rob D.; Hanna, George B.; Takats, Zoltan

    2016-02-01

    In this study, we make a direct comparison between desorption electrospray ionization-mass spectrometry (DESI-MS) and ultraperformance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) platforms for the profiling of glycerophospholipid (GPL) species in esophageal cancer tissue. In particular, we studied the similarities and differences in the range of GPLs detected and the congruency of their relative abundances as detected by each analytical platform. The main differences between mass spectra of the two modalities were found to be associated with the variance in adduct formation of common GPLs, rather than the presence of different GPL species. Phosphatidylcholines as formate adducts in UPLC-ESI-MS accounted for the majority of differences in negative ion mode and alkali metal adducts of phosphatidylcholines in DESI-MS for positive ion mode. Comparison of the relative abundance of GPLs, normalized to a common peak, revealed a correlation coefficient of 0.70 ( P < 0.001). The GPL profile detected by DESI-MS is congruent to UPLC-ESI-MS, which reaffirms the role of DESI-MS for lipidomic profiling and a potential premise for quantification.

  5. Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer.

    PubMed

    Krishnan, Preethi; Ghosh, Sunita; Wang, Bo; Heyns, Mieke; Li, Dongping; Mackey, John R; Kovalchuk, Olga; Damaraju, Sambasivarao

    2016-01-01

    Transfer RNAs (tRNAs, key molecules in protein synthesis) have not been investigated as potential prognostic markers in breast cancer (BC), despite early findings of their dysregulation and diagnostic potential. We aim to comprehensively profile tRNAs from breast tissues and to evaluate their role as prognostic markers (Overall Survival, OS and Recurrence Free Survival, RFS). tRNAs were profiled from 11 normal breast and 104 breast tumor tissues using next generation sequencing. We adopted a Case-control (CC) and Case-Only (CO) association study designs. Risk scores constructed from tRNAs were subjected to univariate and multivariate Cox-proportional hazards regression to investigate their prognostic value. Of the 571 tRNAs profiled, 76 were differentially expressed (DE) and three were significant for OS in the CC approach. We identified an additional 11 tRNAs associated with OS and 14 tRNAs as significant for RFS in the CO approach, indicating that CC alone may not capture all discriminatory tRNAs in prognoses. In both the approaches, the risk scores were significant in the multivariate analysis as independent prognostic factors, and patients belonging to high-risk group were associated with poor prognosis. Our results confirmed global up-regulation of tRNAs in BC and identified tRNAs as potential novel prognostic markers for BC. PMID:27604545

  6. Genome-wide profiling of transfer RNAs and their role as novel prognostic markers for breast cancer

    PubMed Central

    Krishnan, Preethi; Ghosh, Sunita; Wang, Bo; Heyns, Mieke; Li, Dongping; Mackey, John R.; Kovalchuk, Olga; Damaraju, Sambasivarao

    2016-01-01

    Transfer RNAs (tRNAs, key molecules in protein synthesis) have not been investigated as potential prognostic markers in breast cancer (BC), despite early findings of their dysregulation and diagnostic potential. We aim to comprehensively profile tRNAs from breast tissues and to evaluate their role as prognostic markers (Overall Survival, OS and Recurrence Free Survival, RFS). tRNAs were profiled from 11 normal breast and 104 breast tumor tissues using next generation sequencing. We adopted a Case-control (CC) and Case-Only (CO) association study designs. Risk scores constructed from tRNAs were subjected to univariate and multivariate Cox-proportional hazards regression to investigate their prognostic value. Of the 571 tRNAs profiled, 76 were differentially expressed (DE) and three were significant for OS in the CC approach. We identified an additional 11 tRNAs associated with OS and 14 tRNAs as significant for RFS in the CO approach, indicating that CC alone may not capture all discriminatory tRNAs in prognoses. In both the approaches, the risk scores were significant in the multivariate analysis as independent prognostic factors, and patients belonging to high-risk group were associated with poor prognosis. Our results confirmed global up-regulation of tRNAs in BC and identified tRNAs as potential novel prognostic markers for BC. PMID:27604545

  7. A Comparison of DESI-MS and LC-MS for the Lipidomic Profiling of Human Cancer Tissue.

    PubMed

    Abbassi-Ghadi, Nima; Jones, Emrys A; Gomez-Romero, Maria; Golf, Ottmar; Kumar, Sacheen; Huang, Juzheng; Kudo, Hiromi; Goldin, Rob D; Hanna, George B; Takats, Zoltan

    2016-02-01

    In this study, we make a direct comparison between desorption electrospray ionization-mass spectrometry (DESI-MS) and ultraperformance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) platforms for the profiling of glycerophospholipid (GPL) species in esophageal cancer tissue. In particular, we studied the similarities and differences in the range of GPLs detected and the congruency of their relative abundances as detected by each analytical platform. The main differences between mass spectra of the two modalities were found to be associated with the variance in adduct formation of common GPLs, rather than the presence of different GPL species. Phosphatidylcholines as formate adducts in UPLC-ESI-MS accounted for the majority of differences in negative ion mode and alkali metal adducts of phosphatidylcholines in DESI-MS for positive ion mode. Comparison of the relative abundance of GPLs, normalized to a common peak, revealed a correlation coefficient of 0.70 (P < 0.001). The GPL profile detected by DESI-MS is congruent to UPLC-ESI-MS, which reaffirms the role of DESI-MS for lipidomic profiling and a potential premise for quantification. PMID:26466600

  8. Identification of therapeutic targets in ovarian cancer through active tyrosine kinase profiling

    PubMed Central

    Ocaña, Alberto; Pandiella, Atanasio

    2015-01-01

    The activation status of a set of pro-oncogenic tyrosine kinases in ovarian cancer patient samples was analyzed to define potential therapeutic targets. Frequent activation of HER family receptor tyrosine kinases, especially HER2, was observed. Studies in ovarian cancer cell lines confirmed the activation of HER2. Moreover, knockdown of HER2 caused a strong inhibition of their proliferation. Analyses of the action of agents that target HER2 indicated that the antibody drug conjugate trastuzumab-emtansine (T-DM1) caused a substantial antitumoral effect in vivo and in vitro, and potentiated the action of drugs used in the therapy of ovarian cancer. T-DM1 provoked cell cycle arrest in mitosis, and caused the appearance of aberrant mitotic spindles in cells treated with the drug. Biochemical experiments confirmed accumulation of the mitotic markers phospho-Histone H3 and phospho-BUBR1 in cells treated with the drug. Prolonged treatment of ovarian cancer cells with T-DM1 provoked the appearance of multinucleated cells which later led to cell death. Together, these data indicate that HER2 represents an important oncogene in ovarian cancer, and suggest that targeting this tyrosine kinase with T-DM1 may be therapeutically effective, especially in ovarian tumors with high content of HER2. PMID:26336133

  9. Helping the Sick Child Live with Cancer: The Role of the Child Life Worker in At-Home Team Rehabilitation.

    ERIC Educational Resources Information Center

    Tharp, Paulette

    The paper discusses the role of the Child Life Worker as a member of a multidisciplinary team in the rehabilitation of cancer patients and their families when children are involved. It is noted that the concepts can be applied to any chronic pediatric illness or handicapping condition. (Author/SBH)