Ciro, Marco; Bracken, Adrian P; Helin, Kristian
In the past couple of years, several very exciting studies have demonstrated the enormous power of gene-expression profiling for cancer classification and prediction of patient survival. In addition to promising a more accurate classification of cancer and therefore better treatment of patients......, gene-expression profiling can result in the identification of novel potential targets for cancer therapy and a better understanding of the molecular mechanisms leading to cancer....
... Facebook Share on Twitter Your Guide to Understanding Genetic Conditions Search MENU Toggle navigation Home Page Search ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions breast cancer breast cancer Enable ...
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.
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.
U.S. Department of Health & Human Services — The State Cancer Profiles (SCP) web site provides statistics to help guide and prioritize cancer control activities at the state and local levels. SCP is a...
... neoplasm of lung malignant tumor of lung pulmonary cancer pulmonary carcinoma pulmonary neoplasms respiratory carcinoma Related Information How are genetic conditions and genes named? Additional Information & Resources ... Encyclopedia: Lung Cancer--Non-Small Cell Encyclopedia: Lung Cancer--Small Cell ...
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. |
... Cancer Survivorship ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) BLADDER CANCER Sources for This Page American Cancer Society: What Are the Key Statistics for Bladder Cancer? Bryan RT, Hussain SA, James ...
Full Text Available Sebastiano Bordonaro Fabio Raiti, Annamaria Di Mari, Calogera Lopiano, Fabrizio Romano, Vitalinda Pumo, Sebastiano Rametta Giuliano, Margherita Iacono, Eleonora Lanteri, Elena Puzzo, Sebastiano Spada, Paolo TralongoUOC Medical Oncology, RAO, ASP 8 Siracusa, ItalyBackground: Active home-based treatment represents a new model of health care. Chronic treatment requires continuous access to facilities that provide cancer care, with considerable effort, particularly economic, on the part of patients and caregivers. Oral chemotherapy could be limited as a consequence of poor compliance and adherence, especially by elderly patients.Methods: We selected 30 cancer patients referred to our department and treated with oral therapy (capecitabine, vinorelbine, imatinib, sunitinib, sorafenib, temozolomide, ibandronate. This pilot study of oral therapy in the patient’s home was undertaken by a doctor and two nurses with experience in clinical oncology. The instruments used were clinical diaries recording home visits, hospital visits, need for caregiver support, and a questionnaire specially developed by the European Organization for Research and Treatment of Cancer (EORTC, known as the QLQ-C30 version 2.0, concerning the acceptability of oral treatment from the patient’s perspective.Results: This program decreased the need to access cancer facilities by 98.1%, promoted better quality of life for patients, as reflected in increased EORTC QLQ-C30 scores over time, allowing for greater adherence to oral treatment as a result of control of drug administration outside the hospital. This model has allowed treatment of patients with difficult access to care (elderly, disabled or otherwise needed caregivers that in the project represent the majority (78% of these.Conclusions: This model of active home care improves quality of life and adherence with oral therapy, reduces the need to visit the hospital, and consequently decreases the number of lost hours of work on
Pandey, Anjita; Singh, Alok Kumar; Maurya, Sanjeev Kumar; Rai, Rajani; Tewari, Mallika; Kumar, Mohan; Shukla, Hari S
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.
Boom-Poels, P G
This article describes behaviour profiles of psychogeriatric patients participating in some substitute care projects. The behaviour of 55 patients from five residential homes participating in these projects were rated on the Behaviour Rating Scale for Psychogeriatric Inpatients (GIP). These data were compared with GIP-data of two reference groups: elderly people in residential homes and patients in psychogeriatric nursing homes (supervision, intensive care and nursing care requiring patients). Patients in the projects have, compared to the other people in residential homes, more cognitive and social disabilities. Compared to the patients in nursing homes, the patients in the projects have less social, cognitive and psychomotor disabilities, but more emotional problems, like suspicious, melancholic and dependent behaviour. These results show that patients in substitute care projects have a specific behaviour profile. The profile can be used for careful selection of patients in these projects.
Wegmann, Kate M.; Thompson, Aaron M.; Bowen, Natasha K.
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…
Hansson, Eva Helena; Kjaergaard, H; Schmiegelow, K
. Our study highlights the importance of providing hospital-based home care with consideration for the family members' need for the sense of security achieved by home care by experienced paediatric oncology nurses and regular contact with the doctor. In future studies, interviews with children......The study aims to describe the experiences of a hospital-based home care programme in the families of children with cancer. Fourteen parents, representing 10 families, were interviewed about their experiences of a hospital-based home care programme during a 4-month period in 2009 at a university...... hospital in Denmark. Five children participated in all or part of the interview. The interviews were transcribed verbatim and analysed using qualitative content analysis. The findings indicate that hospital-based home care enabled the families to remain intact throughout the course of treatment...
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,
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
Hansson, Eva Helena; Kjaergaard, Hanne; Johansen, Christoffer
BACKGROUND: To assess the feasibility and psychosocial impact of a hospital-based home care (HBHC) program for children with cancer. PROCEDURE: A HBHC program was carried out with 51 children (0-18 years) with cancer to assess its feasibility in terms of satisfaction, care preferences, safety, an...... and the psychosocial burden on the family does not increase. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.......BACKGROUND: To assess the feasibility and psychosocial impact of a hospital-based home care (HBHC) program for children with cancer. PROCEDURE: A HBHC program was carried out with 51 children (0-18 years) with cancer to assess its feasibility in terms of satisfaction, care preferences, safety......, and cost. A controlled trial was conducted to assess children's health-related quality of life (HRQOL) using the parent-reported and self-reported PedsQL Generic Core Scale and PedsQL Cancer Module, and the psychosocial impact on the family by PedsQL Family Impact Module comprising a subsample of 28...
Zalevsky, Zeev; Rudnitsky, Arkady; Sheinman, Victor; Tzoy, Andrey; Toktosunov, Aitmamat; Adashov, Arkady
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.
Hiller, Karsten; Metallo, Christian M
Cancer is a disease of unregulated cell growth and survival, and tumors reprogram biochemical pathways to aid these processes. New capabilities in the computational and bioanalytical characterization of metabolism have now emerged, facilitating the identification of unique metabolic dependencies that arise in specific cancers. By understanding the metabolic phenotype of cancers as a function of their oncogenic profiles, metabolic engineering may be applied to design synthetically lethal therapies for some tumors. This process begins with accurate measurement of metabolic fluxes. Here we review advanced methods of quantifying pathway activity and highlight specific examples where these approaches have uncovered potential opportunities for therapeutic intervention.
Bernards, R.A.; Veer, L.J. van ’t; Dai, H.; Vijver, M.J. van de; He, Y.D.; Hart, A.A.M.; Friend, S.H.
Gruvberger et al. postulate, in their commentary published in this issue of Breast Cancer Research, that our “prognostic gene set may not be broadly applicable to other breast tumor cohorts”, and they suggest that “it may be important to define prognostic expression profiles separately in estrogen r
Sørensen, Kristina Pilekær
Each year approximately 4,800 Danish women are diagnosed with breast cancer. Several clinical and pathological factors are used as prognostic and predictive markers to categorize the patients into groups of high or low risk. Around 90% of all patients are allocated to the high risk group...... clinical courses, and they may be useful as novel prognostic biomarkers in breast cancer. The aim of the present project was to predict the development of metastasis in lymph node negative breast cancer patients by RNA profiling. We collected and analyzed 82 primary breast tumors from patients who...... and the time of event. Previous findings have shown that high expression of the lncRNA HOTAIR is correlated with poor survival in breast cancer. We validated this finding by demonstrating that high HOTAIR expression in our primary tumors was significantly associated with worse prognosis independent...
It is of great importance to identify new cancer genes from the data of large scale genome screenings of gene mutations in cancers. Considering the alternations of some essential functions are indispensable for oncogenesis, we define them as cancer functions and select, as their approximations, a group of detailed functions in GO (Gene Ontology) highly enriched with known cancer genes. To evaluate the efficiency of using cancer functions as features to identify cancer genes, we define, in the screened genes, the known protein kinase cancer genes as gold standard positives and the other kinase genes as gold standard negatives. The results show that cancer associated functions are more efficient in identifying cancer genes than the selection pressure feature. Furthermore, combining cancer functions with the number of non-silent mutations can generate more reliable positive predictions. Finally, with precision 0.42, we suggest a list of 46 kinase genes as candidate cancer genes which are annotated to cancer functions and carry at least 3 non-silent mutations.
Vellone, Ercole; Sinapi, Nadia; Piria, Paola; Bernardi, Francesca M; Dario, Lucia; Brunetti, Annarita
The aim of this study was to investigate the anxiety and depression of cancer patients hospitalized and at home. Using a descriptive, correlational and comparative design and the Roy Adaptation Model, a sample of 80 oncologic patients was studied. Several instruments were used to measure anxiety and depression (HADS), quality of life and symptoms (RSCL), sociodemographic factors, variables connected to the hospitalization, quality of the relationship with health practitioners, family members and friends and the degree of satisfaction for the received information and support. The examined variables were measured on the same patients at hospital and at home. About the 30% of the patients were anxious and depressed. Statistical analysis showed that while anxiety did not change from the hospital to home, depression increased soon after the discharge and decreased over time and after the increasing of the number of hospital access. Anxiety and depression were positively correlated to boredom during the hospitalization, physical symptoms, number of the patients children, and previous anxious and depressive problems. Anxiety and depression were negatively correlated to the ward comfort, the support of health practitioners, family members and friends and the satisfaction for the received information. Differences between this study and the international literature are discussed. Recommendations for the future research and nursing practice are given.
cancer or a history of transurethral resection of the prostate (TURP) for benign prostatic hypertrophy are excluded. Somewhat surprisingly...AD_________________ Award Number: W81XWH-11-1-0451 TITLE: Metabolomic Profiling of Prostate Cancer...29 September 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Metabolomic Profiling of Prostate Cancer Progression During Active Surveillance 5b
Liu, Xiufeng; Whitford, Melinda
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.
Nutritional problems are common in palliative cancer care. Little is known about nutritional problems and nutritional support in home care. AIMS: The primary aim of this thesis was to investigate experiences of nutritional problems and home nutritional support, with a special focus on home parenteral nutrition (HPN), from the perspectives of cancer patients and their family members. Further aims were to investigate the prevalence of nutritional risk and use of nutritional su...
Suzuki, Lalita K; Beale, Ivan L
The content of personal Web home pages created by adolescents with cancer is a new source of information about this population of potential benefit to oncology nurses and psychologists. Individual Internet elements found on 21 home pages created by youths with cancer (14-22 years old) were rated for cancer-related self-presentation, information dissemination, and interpersonal connection. Examples of adolescents' online narratives were also recorded. Adolescents with cancer used various Internet elements on their home pages for cancer-related self-presentation (eg, welcome messages, essays, personal history and diary pages, news articles, and poetry), information dissemination (e.g., through personal interest pages, multimedia presentations, lists, charts, and hyperlinks), and interpersonal connection (eg, guestbook entries). Results suggest that various elements found on personal home pages are being used by a limited number of young patients with cancer for self-expression, information access, and contact with peers.
Neergaard, Mette Asbjørn; Olesen, Frede; Vedsted, Peter;
Background: In most western countries, the majority of palliative cancer patients wish to die at home, where GPs are often deeply involved. However, most research focuses on specialised palliative care, which results in a lack of reliable predictors of home death in primary care. Aim: To analyse...... predictors of home death among deceased palliative cancer patients in a primary care setting. Methods: Using Danish registers, we identified 787 deceased cancer patients and sent a questionnaire to their GPs. The questions concerned the GPs' involvement and the duration of the palliative period at home. We......-of-hours, and whether the GP had had contact with the relatives. Results: 350 questionnaires were filled out. In the preliminary analysis we found that even though many patients died in hospital, this group spent nearly as much of their last time at home as the patients who actually died at home. The analysis...
Perry, G R
This exploratory study measured the degree of loneliness experienced by adult cancer patients. All were in the initial phases of the illness, that is, currently receiving treatment consisting of either chemotherapy or radiation therapy on an outpatient basis and/or recuperating from surgery in the home setting. All were within 100 days of initial diagnosis of cancer. The UCLA Loneliness Scale by Peplau was used in measuring loneliness. In addition, the coping methods of this same group of patients were examined using the Jalowiec Coping Scale to determine predominant methods of coping with the situational crisis imposed by cancer diagnosis and treatment. The instruments were administered in the home or in an outpatient setting and patients were accessed through cancer treatment centers and from oncologists in the southern Illinois area. The study was conducted to determine the prevalence of loneliness, to identify predominant coping methods, and to discern the relationship, if any, between coping methods employed and the degree of loneliness reported by the adult cancer patients. The conceptual framework chosen for the study was taken from the work of Lazarus and Jalowiec with regard to coping; the work of Peplau, Russell, and Cutrone on loneliness formed the conceptual basis for the portion of the study regarding that dimension. A total of 41 cancer patients were surveyed--21 were male and 20 were female. The median age was 60 years, and the mean educational level was 10.5 years. There were significant differences found between loneliness scores by age categories and by marital status, as well as a relationship between membership in organizations and loneliness scores. There were significant relationships found between coping methods (confrontive, emotive, palliative) employed and the degree of loneliness experienced by these cancer patients. Coping methods were also ranked by frequency of use, and interesting patterns emerged--especially noteworthy were group
Minafra, L.; Bravatà, V.; Russo, G.; Ripamonti, M.; Gilardi, M. C.
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.
Minafra, L.; Bravatà, V.; Russo, G.; Ripamonti, M.; Gilardi, M. C. [IBFM CNR - LATO, Cefalù, Segrate (Italy)
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.
Tse, Mimi M Y; Wan, Vanessa T C; Vong, Sinfia K S
The purpose of this exploratory cross-sectional study was to explore the health-related profile and quality of life among older persons living with and without pain in nursing homes. Ten nursing homes were approached, and 535 older persons were invited to join the study from 2009 to 2011. The nursing home residents' demographic information and information regarding their pain situation and the use of oral analgesic drug and nondrug therapy among the older residents with chronic pain were also collected. Residents' physical health (using the Barthel Activities of Daily Living (ADL) and Elderly Mobility Scores); psychologic health, including happiness, life satisfaction, depression, and loneliness (using the Happiness Scale, the Life Satisfaction Scale, the Geriatric Depression Scale, and the UCLA Loneliness Scale); and quality of life were investigated. Among the 535 nursing home residents, 396 (74%) of them suffered from pain, with mean pain scores of 4.09 ± 2.19, indicating medium pain intensity a remaining 139 (26%) reported no pain. The location of pain was mainly in the knees, back and shoulders. Our results demonstrated that, with the exception of the no-pain group (p nursing home residents' pain affected both their psychologic health, including happiness, life satisfaction, and depression, and their physical quality of life. Nevertheless, only one-half of the older persons with pain used oral analgesic drug or nondrug therapy to relieve their pain. Pain had a significant impact on their mobility and ADL, was positively correlated with happiness and life satisfaction, and was negatively correlated with loneliness and depression. Pain management is a high priority in elderly care; as such, innovative and interdisciplinary strategies are necessary to enhance quality of life particularly for older persons living in nursing homes.
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
Gazendam-Donofrio, S.M.; Hoekstra, H.J.; Graaf, W.T.A. van der; Pras, E.; Visser, A.; Huizinga, G.A.; Hoekstra-Weebers, J.E.
GOALS OF WORK: This study examined the quality of life (QoL) of cancer patients diagnosed 1-5 years previously and their spouses, with children 4-18 years living at home. Relationships between parents' QoL and the children's functioning were explored. PATIENTS AND METHODS: 166 cancer patients and th
Gazendam-Donofrio, S.M.; Hoekstra, H.J.; van der Graaf, W.T.A.; Pras, E.; Visser, Annemieke; Huizinga, G.A.; Hoekstra-Weebers, J.E.H.M.
Goals of work This study examined the quality of life (QoL) of cancer patients diagnosed 1-5 years previously and their spouses, with children 4-18 years living at home. Relationships between parents' QoL and the children's functioning were explored. Patients and methods 166 cancer patients and thei
Leichtle, Alexander Benedikt; Nuoffer, Jean-Marc; Ceglarek, Uta; Kase, Julia; Conrad, Tim; Witzigmann, Helmut; Thiery, Joachim; Fiedler, Georg Martin
Mass spectrometry-based serum metabolic profiling is a promising tool to analyse complex cancer associated metabolic alterations, which may broaden our pathophysiological understanding of the disease and may function as a source of new cancer-associated biomarkers. Highly standardized serum samples of patients suffering from colon cancer (n = 59) and controls (n = 58) were collected at the University Hospital Leipzig. We based our investigations on amino acid screening profiles using electrospray tandem-mass spectrometry. Metabolic profiles were evaluated using the Analyst 1.4.2 software. General, comparative and equivalence statistics were performed by R 2.12.2. 11 out of 26 serum amino acid concentrations were significantly different between colorectal cancer patients and healthy controls. We found a model including CEA, glycine, and tyrosine as best discriminating and superior to CEA alone with an AUROC of 0.878 (95% CI 0.815-0.941). Our serum metabolic profiling in colon cancer revealed multiple significant disease-associated alterations in the amino acid profile with promising diagnostic power. Further large-scale studies are necessary to elucidate the potential of our model also to discriminate between cancer and potential differential diagnoses. In conclusion, serum glycine and tyrosine in combination with CEA are superior to CEA for the discrimination between colorectal cancer patients and controls.
Pedersen, Johannes W; Blixt, Ola; Bennett, Eric P
Cancer-associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant post-translational variants of proteins are likely to induce autoantibodies, and changes in O-linked glycosylation represent one of the most important cancer-associated post...... array displaying a comprehensive library of glycopeptides and glycoproteins derived from a panel of human mucins (MUC1, MUC2, MUC4, MUC5AC, MUC6 and MUC7) known to have altered glycosylation and expression in cancer. Seromic profiling of patients with colorectal cancer identified cancer......-associated autoantibodies to a set of aberrant glycopeptides derived from MUC1 and MUC4. The cumulative sensitivity of the array analysis was 79% with a specificity of 92%. The most prevalent of the identified autoantibody targets were validated as authentic cancer immunogens by showing expression of the epitopes in cancer...
Assessment among breast cancer survivors. Oncology 70:190-202 6. Alhola P, Polo-Kantola P. 2007. Sleep deprivation : Impact on cognitive performance ...MEDICAL AND CLINICAL PSYCHOLOGY GRADUATE PROGRAM Name of Student : Briana Todd Date of Examination: May 9, 2014 Time: 9 :00am Place: G252 DECISION OF...million breast cancer survivors in the United States alone and 6.3 internationally (111; 393). The late and long-term effects of cancer and its treatment
Nordly, Mie; Vadstrup, Eva Soelberg; Sjøgren, Per
OBJECTIVE: Due to an urgent need for specialized palliative care (SPC) for patients with advanced cancer, an overview of available information on organization and outcomes of home-based SPC would be valuable. Our systematic review aims to give an overview of available information on the organizat......OBJECTIVE: Due to an urgent need for specialized palliative care (SPC) for patients with advanced cancer, an overview of available information on organization and outcomes of home-based SPC would be valuable. Our systematic review aims to give an overview of available information...... on the organization and outcomes of home-based SPC for patients with advanced cancer. Outcomes related to place of death, survival time, quality of life, performance status, and symptom management are included. METHOD: A PICO process search strategy consisting of terms related to cancer, palliation, and home care...... for patients with advanced cancer, resulting in poor information and a lack of evidence. Generally, home-based SPC seems to have some positive effect on pain and dyspnea, but more high-quality studies are required....
Dhaini, Hassan R; Kobeissi, Loulou
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.
Mitchell, Lori A.; Hirdes, John; Poss, Jeff W.; Slegers-Boyd, Caroline; Caldarelli, Hilary; Martin, Lynn
Background Individuals living in the community with neurological conditions receive the majority of their care from informal caregivers. The purpose of this project was to provide a profile of caregivers of home care clients with neurological conditions. The study also examined prevalence of caregiver distress and the association between neurological conditions and other client and caregiver characteristics with distress. Methods The study population included Canadian home care clients in the...
Frolich, Camilla; Albrechtsen, Reidar; Andersen, Lars Dyrskjøt
PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical...
Perez, Kimberly; Safran, Howard P
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.
Full Text Available Background: The profiles of lipids in normal and cancerous tissues may differ revealing information about cancer development and progression. Lipids being surface active, changes in lipid profiles can manifest as altered surface activity profiles. Langmuir monolayers offer a convenient model for evaluating surface activity of biological membranes. Aims: The aims of this study were to quantify phospholipids and their effects on surface activity of normal and cancerous human cervical tissues as well as to evaluate the role of phosphatidylcholine (PC and sphingomyelin (SM in cervical cancer using Langmuir monolayers. Methods and Materials: Lipid quantification was done using thin layer chromatography and phosphorus assay. Surface activity was evaluated using Langmuir monolayers. Monolayers were formed on the surface of deionized water by spreading tissue organic phase corresponding to 1 mg of tissue and studying their surface pressure-area isotherms at body temperature. The PC and SM contents of cancerous human cervical tissues were higher than those of the normal human cervical tissues. Role of PC and SM were evaluated by adding varying amounts of these lipids to normal cervical pooled organic phase. Statistical analysis: Student′s t-test (p < 0.05 and one-way analysis of variance (ANOVA was used. Results: Our results reveals that the phosphatidylglycerol level in cancerous cervical tissue was nearly five folds higher than that in normal cervical tissue. Also PC and sphingomyelin SM were found to be the major phospholipid components in cancerous and normal cervical tissues respectively. The addition of either 1.5 µg DPPC or 0.5 µg SM /mg of tissue to the normal organic phase changed its surface activity profile to that of the cancerous tissues. Statistically significant surface activity parameters showed that PC and SM have remarkable roles in shifting the normal cervical lipophilic surface activity towards that of cancerous lipophilic
Laura E MacConaill
Full Text Available BACKGROUND: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting. METHODOLOGY: We developed and implemented an optimized mutation profiling platform ("OncoMap" to interrogate approximately 400 mutations in 33 known oncogenes and tumor suppressors, many of which are known to predict response or resistance to targeted therapies. The performance of OncoMap was analyzed using DNA derived from both frozen and FFPE clinical material in a diverse set of cancer types. A subsequent in-depth analysis was conducted on histologically and clinically annotated pediatric gliomas. The sensitivity and specificity of OncoMap were 93.8% and 100% in fresh frozen tissue; and 89.3% and 99.4% in FFPE-derived DNA. We detected known mutations at the expected frequencies in common cancers, as well as novel mutations in adult and pediatric cancers that are likely to predict heightened response or resistance to existing or developmental cancer therapies. OncoMap profiles also support a new molecular stratification of pediatric low-grade gliomas based on BRAF mutations that may have immediate clinical impact. CONCLUSIONS: Our results demonstrate the clinical feasibility of high-throughput mutation profiling to query a large panel of "actionable" cancer gene mutations. In the future, this type of approach may be incorporated into both cancer epidemiologic studies and clinical decision making to specify the use of many targeted anticancer agents.
Lian Xin Liu; Hong Chi Jiang; An Long Zhu; Jin Zhou; Xiu Qin Wang; Min Wu
AIM To describe a liver cancer = specific gene expression profile and to identify genes that showed alteredexpression between liver cancer tissues and their adjacent nearly normal tissues.METHODS The cDNA probes which were labeled with a-32P dATP were synthesized from total RNA ofliver cancer and adjacent normal tissues and hybridized separately to two identical Atlas human cancer eDNAexpression array membranes containing 588 known genes.RESULTS Autoradiographic results were analyzed by specific Atlas ImageTM (version 1. 0) software.Among the 588 genes analyzed, 18 genes were found up-regulated in cancer, including TFDP2, Aktl, E2F-3etc, and 25 genes were down-regulated in cancer, including TDGF1, BAK, LAR, etc. Expression levels ofgenes that associated with the regulation of cell proliferation, apoptosis, differentiation, cell-cellinteraction, invasion regulators and eytokines altered mostly.CONCLUSION The result obtained from Atlas microarray provides a comprehensive liver cancer-specificexpression profile. The results can lead to the identification of liver cancer-specific biomarkers and may behelpful in early diagnosis and dentifiction of target genes for designing rational therapeutic strategies.
Bipin Kumar Sethi
Full Text Available Prolactin has, for long, been associated with galactorrhea and infertility in women while its role in men is largely unknown. Recently, expression of prolactin in various other tissues like the breast, prostate, decidua, and the brain has been recognized. This has led to evaluation of paracrine and autocrine actions of prolactin at these tissues and a possible role in development of various cancers. Increased expression of PRL receptors has also been implicated in carcinogenesis. Breast cancer has the strongest association with increased prolactin and prolactin receptor levels. Prostate cancer also has reported significant association, while the role of prolactin in colorectal, gynecological, laryngeal, and hepatocellular cancers is more tenuous. Prolactin/prolactin receptor pathway has also been implicated in development of resistance to chemotherapy. Thus, the effects of this pathway in carcinogenesis seem widespread. At the same time, they also offer an exciting new approach to hormonal manipulation of cancers, especially the treatment-resistant cancers.
Patil, Ajeetkumar; Bhat, Sujatha; Rai, Lavanya; Kartha, V. B.; Chidangil, Santhosh
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.
Hansson, Helena; Hallström, Inger; Kjaergaard, Hanne
Hospital-based home care (HBHC) is widely applied in Pediatric Oncology. We reviewed the potential effect of HBHC on children's physical health and risk of adverse events, parental and child satisfaction, quality of life of children and their parents, and costs. A search of PubMed, CINAHL...
Shiozawa, Yusuke; Havens, Aaron M.; Jung, Younghun; Ziegler, Anne M.; Pedersen, Elisabeth A.; Wang, Jingcheng; Wang, Jianhua; Lu, Ganwei; Roodman, G. David; Loberg, Robert D.; Pienta, Kenneth J.; Taichman, Russell S.
One of the most life-threatening complications of prostate cancer is skeletal metastasis. In order to develop treatment for metastasis, it is important to understand its molecular mechanisms. Our work in this field has drawn parallels between hematopoietic stem cell and prostate cancer homing to the marrow. Our recent work demonstrated that annexin II expressed by osteoblasts and endothelial cells plays a critical role in niche selection. In this study, we demonstrate that annexin II and its receptor play a crucial role in establishing metastasis of prostate cancer. Prostate cancer cell lines migrate toward annexin II and the adhesion of prostate cancer to osteoblasts and endothelial cells was inhibited by annexin II. By blocking annexin II or its receptor in animal models, short-term and long-term localization of prostate cancers are limited. Annexin II may also facilitate the growth of prostate cancer in vitro and in vivo by the MAPK pathway. These data strongly suggest annexin II and its receptor axis plays a central role in prostate cancer metastasis, and that prostate cancer utilize the hematopoietic stem cell homing mechanisms to gain access to the niche. PMID:18636554
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.
Dumitrescu, Luminita; van den Heuvel-Olaroiu, Marinela; van den Heuvel, Wim J. A.
This study describes the activities and interventions carried out by an at-home palliative care team treating cancer patients who died within two years of being enrolled in a palliative care program. It analyzes which changes in symptoms and pain occurred and which sociodemographic and medical characteristics were related to these changes. The analysis is based on 102 cancer patients. Data were collected through systematic registration during the palliative care process. At enrollment, patien...
Ammerpohl, Ole; Haake, Andrea; Kolarova, Julia; Siebert, Reiner
Epigenetic mechanisms including DNA methylation are fundamental for the regulation of gene expression. Epigenetic alterations can lead to the development and the evolution of malignant tumors as well as the emergence of phenotypically different cancer cells or metastasis from one single tumor cell. Here we describe bisulfite pyrosequencing, a technology to perform quantitative DNA methylation analyses, to detect aberrant DNA methylation in malignant tumors.
Dumitrescu, Luminita; van den Heuvel-Olaroiu, Marinela; van den Heuvel, Wim J. A.
This study describes the activities and interventions carried out by an at-home palliative care team treating cancer patients who died within two years of being enrolled in a palliative care program. It analyzes which changes in symptoms and pain occurred and which sociodemographic and medical chara
Bozzetti, F; Santarpia, L; Pironi, L
BACKGROUND: The role of home parenteral nutrition (HPN) in incurable cachectic cancer patients unable to eat is extremely controversial. The aim of this study is to analyse which factors can influence the outcome. PATIENTS AND METHODS: We studied prospectively 414 incurable cachectic (sub...
Albrechtsen, Reidar; Dyrskjøt, Lars; Rudkjaer, Lise;
PURPOSE: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. EXPERIMENTAL DESIGN: ADAM12...... staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. RESULTS: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined...... by microarray analysis, and the level of ADAM12 mRNA correlated with disease stage. Reverse transcription-PCR, quantitative PCR, and in situ hybridization validated the gene expression results. Using immunohistochemistry, we found ADAM12 protein expression correlated with tumor stage and grade. Finally, ADAM12...
Jang, Eunice Eunhee; Dunlop, Maggie; Wagner, Maryam; Kim, Youn-Hee; Gu, Zhimei
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…
Dimitrios Zardavas; Martine Piccart-Gebhart
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.
Bertucci, François; Finetti, Pascal; Vermeulen, Peter; Van Dam, Peter; Dirix, Luc; Birnbaum, Daniel; Viens, Patrice; Van Laere, Steven
Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer. Despite efforts in the past decade to delineate the molecular biology of IBC by applying high-throughput molecular profiling technologies to clinical samples, IBC remains insufficiently characterized. The reasons for that include limited sizes of the study population, heterogeneity with respect to the composition of the IBC and non-IBC control groups and technological differences across studies. In 2008, the World IBC Consortium was founded to foster collaboration between research groups focusing on IBC. One of the initial projects was to redefine the molecular profile of IBC using an unprecedented number of samples and search for gene signatures associated with survival and response to neo-adjuvant chemotherapy. Here, we provide an overview of all the molecular profiling studies that have been performed on IBC clinical samples to date.
Higginson, Irene J; Wilkinson, Susie
Marie Curie Cancer Care established its nursing service in 1958; however, the service has had little formal evaluation. This study aimed to describe and evaluate the care provided by Marie Curie nurse, and in particular to determine whether patients in their care remained and died at home. Two existing data sets were used: data on all patients referred to the Marie Curie Nursing Services in 147 areas of England, Wales, Scotland and Northern Ireland for 26 months, and data on cancer death registrations in England. A request for a Marie Curie nurse was made for 26,632 patients, 97% of whom had cancer and 11% of whom lived alone. The amount of care provided varied enormously (Marie Curie nurses facilitated home death for many patients. Services need to ensure that mechanisms are in place to achieve data collection. Rigorous prospective evaluation is needed in the future.
Kavita Banker, Bipin Prajapati, Geeta Kedia
Full Text Available Background: Aging is a normal process. The modernization plays a vital role in aging process of an individual. The aged feel a sense of social isolation because of disjunction from various bonds viz work relationships, and diminish of relatives and friends, mobility of children to far off places for jobs. The situation of the elderly still worsens when there is presence of chronic diseases, physical incapacity and financial stringency. Objective: To know the health profile and health related problems of the old age inmates residing at geriatric homes. Material and Methods: A cross sectional study was carried out in geriatric homes of urban and periurban areas of Ahmedabad during January 2008 to January 2009. Result: Out of total 530 inmates, 45.85% were males and 54.15% were females. 93.77% reported one or more health related complaints. 37.4% were obese and 11.9% were underweight. Most common presenting symptoms were: loss of teeth (70%, joint pain (60.2%, impaired vision (44.2%, weakness (34.9%, and insomnia (34%. 82.3% were using spectacles followed by walking sticks (21.7% and denture (12.8%.The main health related problems were osteoarthritis (54.9%, hypertension (54.2%, cataract(16% and diabetes mellitus(14.9%. Conclusion: The study highlighted a high prevalence of morbidity and health related problems in old age groups. We need to strengthen geriatric health care services, social support by people, proper implementation of geriatric related legislation by government and further research like qualitative research to explore the problems of the elderly.
Peeters, J.; Francke, A.L.; Friele, R.D.; Spreeuwenberg, P.; Graaf, de C.; Beek, van A.
Eating profiles" can be defined as types of clients distinguished by combinations of food preferences, consumption patterns, and preferences for ambiance. The purpose of this article is to describe the development and initial testing of an instrument to establish eating profiles of residents of nurs
Wakelam Michael JO
Full Text Available Abstract Background Colorectal cancer is the second most common cause of cancer related death in the developed world. To date, no blood or stool biomarkers with both high sensitivity and specificity for potentially curable early stage disease have been validated for clinical use. SELDI and MALDI profiling are being used increasingly to search for biomarkers in both blood and urine. Both techniques provide information predominantly on the low molecular weight proteome ( Results We collected urine from 67 patients with colorectal cancer and 72 non-cancer control subjects, diluted to a constant protein concentration and generated MALDI and SELDI spectra. The intensities of 19 peaks differed significantly between cancer and non-cancer patients by both t-tests and after adjusting for confounders using multiple linear regressions. Logistic regression classifiers based on peak intensities identified colorectal cancer with up to 78% sensitivity at 87% specificity. We identified and independently quantified 3 of the discriminatory peaks using synthetic stable isotope peptides (an 1885 Da fragment of fibrinogen and hepcidin-20 or ELISA (β2-microglobulin. Conclusion Changes in the urine proteome may aid in the early detection of colorectal cancer.
Johnson, Genevieve Marie
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:…
Weerkamp, Nico J.; Zuidema, Sytse U.; Tissingh, Gerrit; Poels, Petra J. E.; Munneke, Marten; Koopmans, Raymond T. C. M.; Bloem, Bastiaan R.
Objectives To examine the clinical characteristics, motor impairments, and drug treatments of nursing home residents with Parkinson's disease (PD). Design Cross-sectional study. Setting Nursing homes in the southeast of the Netherlands. Participants Nursing home residents with PD and a Mini-Mental S
Peoples, Hanne; Brandt, Åse; Wæhrens, Eva Elisabet Ejlersen;
in the study. The participants were consecutively recruited from a Danish university hospital. Qualitative interviews were performed at the homes of the participants. Content analysis was applied to the data. Results: Managing occupations were manifested in two main categories; 1) Conditions influencing...... limited research that specifically explores how these occupational difficulties are managed. Objective: To describe and explore how people with advanced cancer manage occupations when living at home. Material and methods: A sub-sample of 73 participants from a larger occupational therapy project took part...
Peoples, Hanne; Brandt, Åse; Wæhrens, Eva Elisabet Ejlersen;
university hospital. Qualitative interviews were performed in the participant’s homes. Interviews were audio recorded and transcribed verbatim. Information on demographic and use of social service was included. Thematic and content analysis were performed. Results: The analysis resulted in a core category......, there are limited research that more specifically explore how these are managed. The objective was to describe and explore how people with advanced cancer manage occupations at home. Material and methods: A qualitative descriptive design was applied. 73 participants were consecutively recruited from a Danish...
Makoukji, Joelle; Makhoul, Nadine J.; Khalil, Maya; El-Sitt, Sally; Aldin, Ehab Saad; Jabbour, Mark; Boulos, Fouad; Gadaleta, Emanuela; Sangaralingam, Ajanthah; Chelala, Claude; Boustany, Rose-Mary; Tfayli, Arafat
Breast cancer is commonest cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. Molecular alterations in breast cancer are complex and involve cross-talk between multiple signaling pathways. The aim of this study is to extract a unique mRNA fingerprint of breast cancer in Lebanese women using microarray technologies. Gene-expression profiles of 94 fresh breast tissue samples (84 cancerous/10 non-tumor adjacent samples) were analyzed using GeneChip Human Genome U133 Plus 2.0 arrays. Quantitative real-time PCR was employed to validate candidate genes. Differentially expressed genes between breast cancer and non-tumor tissues were screened. Significant differences in gene expression were established for COL11A1/COL10A1/MMP1/COL6A6/DLK1/S100P/CXCL11/SOX11/LEP/ADIPOQ/OXTR/FOSL1/ACSBG1 and C21orf37. Pathways/diseases representing these genes were retrieved and linked using PANTHER®/Pathway Studio®. Many of the deregulated genes are associated with extracellular matrix, inflammation, angiogenesis, metastasis, differentiation, cell proliferation and tumorigenesis. Characteristics of breast cancers in Lebanese were compared to those of women from Western populations to explain why breast cancer is more aggressive and presents a decade earlier in Lebanese victims. Delineating molecular mechanisms of breast cancer in Lebanese women led to key genes which could serve as potential biomarkers and/or novel drug targets for breast cancer. PMID:27857161
Lee, Eun Joo; Gusev, Yuriy; Jiang, Jinmai; Gerard J Nuovo; Lerner, Megan R; Frankel, Wendy L.; Morgan, Daniel L.; Postier, Russell G.; Brackett, Daniel J; Schmittgen, Thomas D.
microRNAs are functional, 22 nt, noncoding RNAs that negatively regulate gene expression. Disturbance of microRNA expression may play a role in the initiation and progression of certain diseases. A microRNA expression signature has been identified that is associated with pancreatic cancer. This has been accomplished with the application of real-time PCR profiling of over 200 microRNA precursors on specimens of human pancreatic adenocarcinoma, paired benign tissue, normal pancreas, chronic pan...
Meropol, Neal J; Daly, Mary B; Vig, Hetal S; Manion, Frank J; Manne, Sharon L; Mazar, Carla; Murphy, Camara; Solarino, Nicholas; Zubarev, Vadim
We examined the feasibility of home videoconferencing for providing cancer genetic education and risk information to people at risk. Adults with possible hereditary colon or breast and ovarian cancer syndromes were offered Internet-based counselling. Participants were sent web cameras and software to install on their home PCs. They watched a prerecorded educational video and then took part in a live counselling session with a genetic counsellor. A total of 31 participants took part in Internet counselling sessions. Satisfaction with counselling was high in all domains studied, including technical (mean 4.3 on a 1-5 scale), education (mean 4.7), communication (mean 4.8), psychosocial (mean 4.1) and overall (mean 4.2). Qualitative data identified technical aspects that could be improved. All participants reported that they would recommend Internet-based counselling to others. Internet-based genetic counselling is feasible and associated with a high level of satisfaction among participants.
Willmann, Lucas; Schlimpert, Manuel; Halbach, Sebastian; Erbes, Thalia; Stickeler, Elmar; Kammerer, Bernd
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.
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.
Shen, Yufeng; Tolić, Nikola; Liu, Tao; Zhao, Rui; Petritis, Brianne O.; Gritsenko, Marina A.; Camp, David G.; Moore, Ronald J.; Purvine, Samuel O.; Esteva, Francisco J.; Smith, Richard D.
Background Cancer invasion and metastasis are closely associated with activities within the degradome; however, little is known about whether these activities can be detected in the blood of cancer patients. Methodology and Principal Findings The peptidome-degradome profiles of pooled blood plasma sampled from 15 breast cancer patients (BCP) and age, race, and menopausal status matched control healthy persons (HP) were globally characterized using advanced comprehensive separations combined with tandem Fourier transform mass spectrometry and new data analysis approaches that facilitated top-down peptidomic analysis. The BCP pool displayed 71 degradome protein substrates that encompassed 839 distinct peptidome peptides. In contrast, the HP 50 degradome substrates found encompassed 425 peptides. We find that the ratios of the peptidome peptide relative abundances can vary as much as >4000 fold between BCP and HP. The experimental results also show differential degradation of substrates in the BCP sample in their functional domains, including the proteolytic and inhibitory sites of the plasmin-antiplasmin and thrombin-antithrombin systems, the main chains of the extracellular matrix protection proteins, the excessive degradation of innate immune system key convertases and membrane attack complex components, as well as several other cancer suppressor proteins. Conclusions Degradomics-peptidomics profiling of blood plasma is highly sensitive to changes not evidenced by conventional bottom-up proteomics and potentially provides unique signatures of possible diagnostic utility. PMID:20976186
Full Text Available BACKGROUND: Cancer invasion and metastasis are closely associated with activities within the degradome; however, little is known about whether these activities can be detected in the blood of cancer patients. METHODOLOGY AND PRINCIPAL FINDINGS: The peptidome-degradome profiles of pooled blood plasma sampled from 15 breast cancer patients (BCP and age, race, and menopausal status matched control healthy persons (HP were globally characterized using advanced comprehensive separations combined with tandem Fourier transform mass spectrometry and new data analysis approaches that facilitated top-down peptidomic analysis. The BCP pool displayed 71 degradome protein substrates that encompassed 839 distinct peptidome peptides. In contrast, the HP 50 degradome substrates found encompassed 425 peptides. We find that the ratios of the peptidome peptide relative abundances can vary as much as >4000 fold between BCP and HP. The experimental results also show differential degradation of substrates in the BCP sample in their functional domains, including the proteolytic and inhibitory sites of the plasmin-antiplasmin and thrombin-antithrombin systems, the main chains of the extracellular matrix protection proteins, the excessive degradation of innate immune system key convertases and membrane attack complex components, as well as several other cancer suppressor proteins. CONCLUSIONS: Degradomics-peptidomics profiling of blood plasma is highly sensitive to changes not evidenced by conventional bottom-up proteomics and potentially provides unique signatures of possible diagnostic utility.
Liu, Xiufeng; Whitford, Melinda
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…
Full Text Available 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.
Koshikawa, Takafumi; Shimoyama, Naohito
Multi-disciplinary team work among visiting doctors, nurses, care managers and pharmacists located close to the patient's home is essential for smooth transition of a palliative care patient from hospital care to palliative home care and should be set up prior to the patient's discharge from the hospital. Palliative home care physicians should have knowledge of the fundamental support by the government to spare excessive cost to the patients. As for cancer pain management, opioid-centered analgesic therapies have lead to better quality home care for patients. In Japan, although oxycodone SRs and fentanyl patches are available besides morphine, there is no rescue opioid other than morphine. On the other hand, some cancer pain refractory to opioids such as neuropathic cancer pain should be carefully treated by adjuvant analgesics in conjunction with non-pharmacological treatments.
Hoess, Victoria; Bachler, Adi; Ostermann, Herwig; Staudinger, Roland
The call to enlarge or merge nursing homes in order to lower costs rests on the assumption that economies of scale exist within the cost structure of these homes. Economies of scale means that an increasing number of residents will reduce the costs per person needing care. However, the existence and the extent of economies of scale as such in nursing homes are the subject of controversy because studies of this issue performed in nursing homes up to now have yielded contradictory results. In this study, researchers demonstrated economies of scale in Tyrolean, Austria, nursing homes and showed that the composition of the nursing home residents in respect to their care needs influences the development of the average costs. Changing the size of the facility and/or influencing the average care level can have a considerable influence on the progression of average costs in nursing homes. Cost reductions can be achieved by increasing the size of the facility or by improved distribution of the care levels of the persons in need of care.
Full Text Available In the United States, mortality rates from pancreatic cancer (PCa have not changed significantly over the past 50 years. This is due, in part, to the lack of early detection methods for this particularly aggressive form of cancer. The objective of this study was to use highthroughput protein profiling technology to identify biomarkers in the serum proteome for the early detection of resectable PCa. Using surface-enhanced laser desorption/ionization mass spectrometry, protein profiles were generated from sera of 49 PCa patients and 54 unaffected individuals after fractionation on an anion exchange resin. The samples were randomly divided into a training set (69 samples and test set (34 samples, and two multivariate analysis procedures, classification and regression tree and logistic regression, were used to develop classification models from these spectral data that could distinguish PCa from control serum samples. In the test set, both models correctly classified all of the PCa patient serum samples (100% sensitivity. Using the decision tree algorithm, a specificity of 93.5% was obtained, whereas the logistic regression model produced a specificity of 100%. These results suggest that high-throughput proteomics profiling has the capacity to provide new biomarkers for the early detection and diagnosis of PCa.
Kinnari, Päivi J; Hyvönen, Maija L K; Mäkilä, Ermei M; Kaasalainen, Martti H; Rivinoja, Antti; Salonen, Jarno J; Hirvonen, Jouni T; Laakkonen, Pirjo M; Santos, Hélder A
Tumour targeting nanoparticles (NPs) have demonstrated great potential for enhancing anticancer drug delivery to tumour sites and for reducing the side effects of chemotherapy. However, many nanoparticulate delivery systems still lack efficient tumour accumulation. In this work, we present a porous silicon (PSi) nanovector functionalized with a tumour-homing peptide, which targets the mammary-derived growth inhibitor (MDGI) expressing cancer cells both in vitro and in vivo, thereby enhancing the accumulation of the NPs in the tumours. We demonstrated that the tumour homing peptide (herein designated as CooP) functionalized thermally hydrocarbonized PSi (THCPSi) NPs homed specifically to the subcutaneous MDGI-expressing xenograft tumours. The THCPSi-CooP NPs were stable in human plasma and their uptake by MDGI-expressing cancer cells measured by confocal microscopy and flow cytometry was significantly increased compared to the non-functionalized THCPSi NPs. After intravenous injections into nude mice bearing MDGI-expressing tumours, effective targeting was detected and THCPSi-CooP NPs showed ~9-fold higher accumulation in the tumour site compared to the control THCPSi NPs. Accumulation of both NPs in the vital organs was negligible.
Azim, Hatem A; Brohée, Sylvain; Peccatori, Fedro A; Desmedt, Christine; Loi, Sherene; Lambrechts, Diether; Dell'Orto, Patrizia; Majjaj, Samira; Jose, Vinu; Rotmensz, Nicole; Ignatiadis, Michail; Pruneri, Giancarlo; Piccart, Martine; Viale, Giuseppe; Sotiriou, Christos
Breast cancer during pregnancy is rare and is associated with relatively poor prognosis. No information is available on its biological features at the genomic level. Using a dataset of 54 pregnant and 113 non-pregnant breast cancer patients, we evaluated the pattern of hot spot somatic mutations and did transcriptomic profiling using Sequenom and Affymetrix respectively. We performed gene set enrichment analysis to evaluate the pathways associated with diagnosis during pregnancy. We also evaluated the expression of selected cancer-related genes in pregnant and non-pregnant patients and correlated the results with changes occurring in the normal breast using a pregnant murine model. We finally investigated aberrations associated with disease-free survival (DFS). No significant differences in mutations were observed. Of the total number of patients, 18.6% of pregnant and 23% of non-pregnant patients had a PIK3CA mutation. Around 30% of tumors were basal, with no differences in the distribution of breast cancer molecular subtypes between pregnant and non-pregnant patients. Two pathways were enriched in tumors diagnosed during pregnancy: the G protein-coupled receptor pathway and the serotonin receptor pathway (FDR pregnancy had higher expression of PD1 (PDCD1; P=0.015), PDL1 (CD274; P=0.014), and gene sets related to SRC (P=0.004), IGF1 (P=0.032), and β-catenin (P=0.019). Their expression increased almost linearly throughout gestation when evaluated on the normal breast using a pregnant mouse model underscoring the potential effect of the breast microenvironment on tumor phenotype. No genes were associated with DFS in a multivariate model, which could be due to low statistical power. Diagnosis during pregnancy impacts the breast cancer transcriptome including potential cancer targets.
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
Yu, Kaixian; Sang, Qing-Xiang Amy; Lung, Pei-Yau; Tan, Winston; Lively, Ty; Sheffield, Cedric; Bou-Dargham, Mayassa J.; Liu, Jun S.; Zhang, Jinfeng
Choosing the optimal chemotherapy regimen is still an unmet medical need for breast cancer patients. In this study, we reanalyzed data from seven independent data sets with totally 1079 breast cancer patients. The patients were treated with three different types of commonly used neoadjuvant chemotherapies: anthracycline alone, anthracycline plus paclitaxel, and anthracycline plus docetaxel. We developed random forest models with variable selection using both genetic and clinical variables to predict the response of a patient using pCR (pathological complete response) as the measure of response. The models were then used to reassign an optimal regimen to each patient to maximize the chance of pCR. An independent validation was performed where each independent study was left out during model building and later used for validation. The expected pCR rates of our method are significantly higher than the rates of the best treatments for all the seven independent studies. A validation study on 21 breast cancer cell lines showed that our prediction agrees with their drug-sensitivity profiles. In conclusion, the new strategy, called PRES (Personalized REgimen Selection), may significantly increase response rates for breast cancer patients, especially those with HER2 and ER negative tumors, who will receive one of the widely-accepted chemotherapy regimens. PMID:28256629
Schou-Andersen, Marianne; Ullersted, Maria P; Jensen, Anders Bonde;
INTRODUCTION: An important element in end-of-life care advocacy is to meet patients' end-of-life preferences. Most Scandinavian patients die in hospitals even though the majority prefers to die at home. Earlier studies have shown socio-economic differences in relation to dying at home, but more...... qualifies prior studies on preferences for end-of-life care and advocates for a more nuanced picture of the subject. Advocacy in end-of-life nursing recommends optimising active listening and communication skills striving towards more patients' preferences in all settings may be heard and fulfilled....... relatives of deceased patients who died of cancer in Denmark in 2006. Bereaved relatives were asked to state patient's preference concerning place of death at the beginning and end of the palliative period. These data were recently combined with updated, extensive demographic and socio-economic data from...
Full Text Available Paolo Tralongo1, Francesco Ferraù2, Nicolò Borsellino3, Francesco Verderame4, Michele Caruso5, Dario Giuffrida6, Alfredo Butera7, Vittorio Gebbia81Medical Oncology Unit, Azienda Sanitaria Provinciale, Siracusa; 2Medical Oncology Unit, Ospedale San Vincenzo, Taormina; 3Medical Oncology Unit, Ospedale Buccheri La Ferla, Palermo; 4Medical Oncology Unit, Ospedale Giovanni Paolo II, Sciacca; 5Medical Oncology Unit, Istituto Humanitas, Catania; 6Medical Oncology Unit, Istituto Oncologico del Mediterraneo, Catania; 7Medical Oncology Unit, Ospedale San Giovanni di Dio, Agrigento; 8Medical Oncology Unit, Dipartimento Oncologico, La Maddalena, Università degli Studi, Palermo, ItalyAbstract: 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.Keywords: cancer, home care
Roblin, Douglas W.; Weingart, Saul N.; Houlahan, Kathleen E.; Degar, Barbara; Billett, Amy; Keuker, Christopher; Biggins, Colleen; Li, Justin; Wasilewski, Karen; Mazor, Kathleen M.
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
Zhu, Jiangjiang; Djukovic, Danijel; Deng, Lingli; Gu, Haiwei; Himmati, Farhan; Chiorean, E Gabriela; Raftery, Daniel
Colorectal cancer (CRC) is one of the most prevalent and deadly cancers in the world. Despite an expanding knowledge of its molecular pathogenesis during the past two decades, robust biomarkers to enable screening, surveillance, and therapy monitoring of CRC are still lacking. In this study, we present a targeted liquid chromatography-tandem mass spectrometry-based metabolic profiling approach for identifying biomarker candidates that could enable highly sensitive and specific CRC detection using human serum samples. In this targeted approach, 158 metabolites from 25 metabolic pathways of potential significance were monitored in 234 serum samples from three groups of patients (66 CRC patients, 76 polyp patients, and 92 healthy controls). Partial least-squares-discriminant analysis (PLS-DA) models were established, which proved to be powerful for distinguishing CRC patients from both healthy controls and polyp patients. Receiver operating characteristic curves generated based on these PLS-DA models showed high sensitivities (0.96 and 0.89, respectively, for differentiating CRC patients from healthy controls or polyp patients), good specificities (0.80 and 0.88), and excellent areas under the curve (0.93 and 0.95). Monte Carlo cross validation was also applied, demonstrating the robust diagnostic power of this metabolic profiling approach.
Schaffrath Rosario, A.; Heid, I.M.; Kreuzer, M.; Heinrich, J.; Kreienbrock, L.; Wichmann, H.E. [GSF-National Research Center for Environment and Health, Inst. of Epidemiology, Neuherberg (Germany)
Studies on underground miners have shown an increased risk of lung cancer after exposure to high doses of radon and radon daughters. However, in the range of typical indoor radon exposures, there are still some uncertainties about the strength of the association between radon exposure and the risk of lung cancer. Since 1990, population-based epidemiological studies have been performed in various countries in North America, Europe, and China. The pooled analysis of two large German case-control studies on the lung cancer risk due to radon in homes is described. The analysis is based on an extended dataset compared to previous publications, including 2,963 lung cancer cases and 4,232 population controls. A linear increase in the relative lung cancer risk of 0.10 (95% CI -0.02 to 0.39) is found. The risk estimates tend to be higher when measurement error in the radon concentrations is reduced. Furthermore, an outlook is given on the activities regarding the pooling of radon studies worldwide. (orig.)
Viveki, R G; Halappanavar, A B; Joshi, A V; Pujar, Kirankumar; Patil, Sandhya
A new trend of admitting more and more senior citizens hailing from the Indian middle class background to old age homes is being observed in recent times. The objectives of this study were to study sociodemographic dimensions and common health problems of inmates of old age homes and to know various reasons for their admissions and their leisure time activities in old age homes. The present cross-sectional study was conducted during March and April 2010 in 4 different old age homes in and around Belgaum city, North Karnataka, by interviewing the inmates of old age homes using predesigned, pretested, structured questionnaire followed by thorough clinical examination and haemoglobin estimation by Sahli's method. The collected data was compiled and analysed using SPSS software version 14. Out of 73 elderly, 54 were females (74.0%). Majority were in the age group of 61-70 years (50.7%) and 56 were belonging to nuclear family (76.7%). Thirty-nine inmates were widow/widower (53.4%) and 42 were having no children (57.5%). Forty-seven inmates were admitted as there was nobody to take care of them (64.4%). Common health problems observed were locomotive/joint and muscle disorders (35.6%), hypertension (34.2%), diabetes mellitus (26.0%), respiratory disorders (23.3%), hearing loss (21.9%) etc. Forty-nine were having normal body mass index (67.1%) while 19.2% were underweight. Majority were having haemoglobin levels between 10-12 g/dl (58.9%). Old age homes definitely will enable the elderly to remain sociopsychologically healthy and lead active lives if effective medical and emotional support is given.
Maruyama, Michio; Nagahama, Takeshi; Sugano, Norihide; Satoh, Eigo; Maruyama, Shouji; Tanami, Hideo; Chiba, Tetsuma; Murakata, Ayano; Mitsuhashi, Yosuke; Uehira, Daisuke; Akazawa, Naoya; Suzuki, Keiichirou
In over the 10 years from 2000-2010, 21 gastric cancer patients received loco-regional chemotherapy with home enteral nutrition (HEN) at an outpatient clinic because of insufficient oral intake. These loco-regional chemotherapy regimens consisted of 5 intra-aortic chemotherapies, 4 hepato-arterial infusions and 12 intra-peritoneal chemotherapies. Five out of 8 cases that had measurable lesions showed PR, and 3 cases revealed PD. The patients received HEN with peptide central formula, 400-1,200 kcal/day in night time. The average duration of HEN was 12.9 months. The post-operative nutritional management was needed for continuation and securing of outpatient chemotherapy. The author reported an experience of the outpatient loco-regional chemotherapy with HEN for the gastric cancer patients who could not eat a sufficient volume of food.
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
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.
Erk, van M.J.; Krul, C.A.M.; Caldenhoven, E.; Stierum, R.H.; Peters, W.H.; Woutersen, R.A.; Ommen, van B.
Interest in mechanisms of colon cancer prevention by food compounds is strong and research in this area is often performed with cultured colon cancer cells. In order to assess utility for screening of potential cancer-preventive (food) compounds, expression profiles of 14 human cell lines derived fr
Erk, M.J. van; Krul, C.A.; Caldenhoven, E.; Stierum, R.H.; Peters, W.H.M.; Woutersen, R.A.; Ommen, B.
Interest in mechanisms of colon cancer prevention by food compounds is strong and research in this area is often performed with cultured colon cancer cells. In order to assess utility for screening of potential cancer-preventive (food) compounds, expression profiles of 14 human cell lines derived fr
Full Text Available The concept of cancer stem cells (CSCs claims that colorectal carcinomas (CRCs, like normal colorectal epithelium, are organized hierarchically and contain a subpopulation of qualitatively distinct cancer cells. The expression of distinctive surface markers or of certain enzymes is a prerequisite for the isolation and characterization of the CSC population. With respect to CRCs, putative CSCs can be identified by leucine-rich-repeat-containing G-protein-coupled receptor 5 (Lgr5, also known as G-protein-coupled receptor 49, Gpr49. However, the precise function of the intestinal stem cell marker Lgr5 in CRCs remains largely unknown. We silenced LGR5 expression in SW480 CRC cells via lentiviral shRNA constructs. This led to the depletion of a morphologically distinct subpopulation of SW480 CRC cells. Microarray gene expression profiling revealed a down-regulation of NOTCH signaling upon LGR5 silencing that could be confirmed by immunohistochemistry. Furthermore, we induced inflammation-driven colon tumors in Lgr5-EGFP-IRES-Cre-ERT2 mice via administration of azoxymethane and dextrane sodium sulfate. The induced tumors were flow-sorted into fractions of epithelial cells that expressed high or low levels of Lgr5 and were characterized using gene expression profiling. Lgr5 high tumor cells showed higher levels of several stem cell-associated genes and higher Wnt signaling than Lgr5 low tumor cells and Lgr5 high normal stem cells. Here we provide a thorough description of our two gene expression datasets including quality control checks uploaded to Gene Expression Omnibus database (data accession number: GSE46200. The analysis and interpretation of our gene expression data and related results have been published recently by Hirsch and colleagues in Carcinogenesis in 2014.
Petti, Stefano; Scully, Crispian
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.
Ashkani, Jahanshah; Naidoo, Kevin J.
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.
Full Text Available Introduction: The home meals service (HMS is a little-developed resource in the Basque Country, and is dependent on social services. The aim of this study is to establish the nutritional status, eating habits and main social and healthcare characteristics of the users of this service.Material and Methods: A descriptive and transversal study carried out in 2 phases: (a phase 1: an assessment of nutritional status and eating habits using an abbreviated version of the Mini Nutritional Assessment and a questionnaire on food consumption. (b phase 2: the assessment of the dependency risk at home and quality of life related to health by means of Barber and EuroQoL-5D questionnaires.Results: Eighty users (35 men, 45 women fulfilled the criteria for inclusion; average age: 83.62 years (± 5.53. Nutritional status: the prevalence of malnutrition was 11% and that of risk of malnutrition 39%. Eating habits: the meal provided guaranteed a minimal provision of legumes, pasta, rice or potatoes (once or twice a week, fish (once or twice a week, and meat (three or four times a week. In spite of this, the frequency of consumption of vegetables, fish, rice, eggs or meat was less than recommended in over 70% of the group. Social and healthcare profile: 127 users (60 men, 67 women took part; average age: 83.82 years (± 6.17. Barber’s questionnaire: living alone: 48%; housebound through illness: 20%. Poor hearing: 44%; poor sight: 34%; although: 30% needed help, 95% were receiving support. EuroQoL-5D: Serious problems reported: 4.7% had difficulties with mobility; 7.9% with personal care; 23.6% had problems with carrying out daily activities; 15% reported pain or discomfort; 3.9% anxiety/depression. Perceived health status: 32.3% considered their health to be good or very good, 34,6% fair, and 33% bad or very bad.Conclusions: The group studied consists of a vulnerable people, with social and health problems and more malnutrition than the older population living at
... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Tumor... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer...
Gronseth, Evangeline; And Others
Data acquired in personal interviews administered to physicians and nurses who participated in the first year of the Home Care for the Child with Cancer project provided descriptions of individual sources of social support. The results reveal a range of supportive mechanisms and networks within varied institutional contexts. (Author)
Full Text Available Abstract Background Basal breast cancers (BCs represent ~15% of BCs. Although overall poor, prognosis is heterogeneous. Identification of good- versus poor-prognosis patients is difficult or impossible using the standard histoclinical features and the recently defined prognostic gene expression signatures (GES. Kinases are often activated or overexpressed in cancers, and constitute targets for successful therapies. We sought to define a prognostic model of basal BCs based on kinome expression profiling. Methods DNA microarray-based gene expression and histoclinical data of 2515 early BCs from thirteen datasets were collected. We searched for a kinome-based GES associated with disease-free survival (DFS in basal BCs of the learning set using a metagene-based approach. The signature was then tested in basal tumors of the independent validation set. Results A total of 591 samples were basal. We identified a 28-kinase metagene associated with DFS in the learning set (N = 73. This metagene was associated with immune response and particularly cytotoxic T-cell response. On multivariate analysis, a metagene-based predictor outperformed the classical prognostic factors, both in the learning and the validation (N = 518 sets, independently of the lymphocyte infiltrate. In the validation set, patients whose tumors overexpressed the metagene had a 78% 5-year DFS versus 54% for other patients (p = 1.62E-4, log-rank test. Conclusions Based on kinome expression, we identified a predictor that separated basal BCs into two subgroups of different prognosis. Tumors associated with higher activation of cytotoxic tumor-infiltrative lymphocytes harbored a better prognosis. Such classification should help tailor the treatment and develop new therapies based on immune response manipulation.
Cousin, Sophie; Grellety, Thomas; Toulmonde, Maud; Auzanneau, Céline; Khalifa, Emmanuel; Laizet, Yec'han; Tran, Kevin; Le Moulec, Sylvestre; Floquet, Anne; Garbay, Delphine; Robert, Jacques; Hostein, Isabelle; Soubeyran, Isabelle; Italiano, Antoine
Previous precision medicine studies have investigated conventional molecular techniques and/or limited sets of gene alterations. The aim of this study was to describe the impact of the next-generation sequencing of the largest panel of genes used to date in tumour tissue and blood in the context of institutional molecular screening programmes. DNA analysis was performed by next-generation sequencing using a panel of 426 cancer-related genes and by comparative genomic hybridization from formalin-fixed and paraffin-embedded archived tumour samples when available or from fresh tumour samples. Five hundred sixty-eight patients were enrolled. The median number of prior lines of treatment was 2 (range 0-9). The most common primary tumour types were lung (16.9%), colorectal (14.4%), breast (10.6%), ovarian (10.2%) and sarcoma (10.2%). The median patient age was 63 years (range 19-88). A total of 292 patients (51.4%) presented with at least one actionable genetic alteration. The 20 genes most frequently altered were TP53, CDKN2A, KRAS, PTEN, PI3KCA, RB1, APC, ERBB2, MYC, EGFR, CDKN2B, ARID1A, SMAD4, FGFR1, MDM2, BRAF, ATM, CCNE1, FGFR3 and FRS2. One hundred fifty-nine patients (28%) were included in early phase trials. The treatment was matched with a tumour profile in 86 cases (15%). The two main reasons for non-inclusion were non-progressive disease (31.5%) and general status deterioration (25%). Twenty-eight percent of patients presented with a growth modulation index (time to progression under the early phase trial treatment/time to progression of the previous line of treatment) >1.3.Extensive molecular profiling using high-throughput techniques allows for the identification of actionable mutations in the majority of cases and is associated with substantial clinical benefit in up to one in four patients.
Bathen Tone F
Full Text Available Abstract Background Combining gene expression microarrays and high resolution magic angle spinning magnetic resonance spectroscopy (HR MAS MRS of the same tissue samples enables comparison of the transcriptional and metabolic profiles of breast cancer. The aim of this study was to explore the potential of combining these two different types of information. Methods Breast cancer tissue from 46 patients was analyzed by HR MAS MRS followed by gene expression microarrays. Two strategies were used to combine the gene expression and metabolic data; first using multivariate analyses to identify different groups based on gene expression and metabolic data; second correlating levels of specific metabolites to transcripts to suggest new hypotheses of connections between metabolite levels and the underlying biological processes. A parallel study was designed to address experimental issues of combining microarrays and HR MAS MRS. Results In the first strategy, using the microarray data and previously reported molecular classification methods, the majority of samples were classified as luminal A. Three subgroups of luminal A tumors were identified based on hierarchical clustering of the HR MAS MR spectra. The samples in one of the subgroups, designated A2, showed significantly lower glucose and higher alanine levels than the other luminal A samples, suggesting a higher glycolytic activity in these tumors. This group was also enriched for genes annotated with Gene Ontology (GO terms related to cell cycle and DNA repair. In the second strategy, the correlations between concentrations of myo-inositol, glycine, taurine, glycerophosphocholine, phosphocholine, choline and creatine and all transcripts in the filtered microarray data were investigated. GO-terms related to the extracellular matrix were enriched among the genes that correlated the most to myo-inositol and taurine, while cell cycle related GO-terms were enriched for the genes that correlated the most
Aline Lima Ribeiro
Full Text Available This study aimed to understand the concepts of family members of patients with cancer, who were inserted and guided by the actions of an extension project aimed at patients with cancer and their families, about the home care given to them, during the treatment phase and progression of the disease. This is an evaluative qualitative research conducted with six family members from June to October, 2013, through semi-structured interviews, analyzed by the method of content analysis. Three categories emerged: the support of nurses in coping with the disease, creating a bond with the patients and their families and nursing as a link to social support networks. It was understood that the health monitoring in the home context gave to the families and patients support and safety to handle concerns that cancer brought into their lives.
Okur, Aysu Ceren; Erkoc, Pelin; Kizilel, Seda
Targeting cell microenvironment via nano-particle based therapies holds great promise for the treatment of various diseases. One of the main challenges in targeted delivery of nanoparticles for cancer therapy is the reduced localization of delivery vehicles to the tumor site. The therapeutic efficacy of drugs can be improved by recruiting delivery vehicles towards specific region of tumorigenesis in the body. Here, we demonstrate an effective approach in creating PEG particles via water-in-water emulsion technique with a tumor-homing peptide CREKA functionalization. The CREKA conjugated hydrogel nanoparticles were found to be more effective at inducing Doxorubicin (DOX)-mediated apoptosis compared to that of particles conjugated with laminin peptide IKVAV. Fluorescence intensity analysis on confocal micrographs suggested significantly higher cellular uptake of CREKA conjugated PEG particles than internalization of nanoparticles in other groups. We observed that fibrin binding ability of PEG particles could be increased up to 94% through CREKA conjugation. Our results suggest the possibility of cancer cell targeting via CREKA-functional PEG nanoparticles.
Levenstein, Phyllis; Phillips, Juliet R.
This report examines the Family Cognitive Profile Study which provided for the collection and analysis of data regarding the IQ gains of children enrolled in the Mother Child Home Program (MCHP). The existence of siblings among the subjects of the MCHP was noted by the Verbal Interaction Project (VIP), the research organization responsible for…
Full Text Available Abstract Background Breast cancer is a heterogeneous disease for which prognosis and treatment strategies are largely governed by the receptor status (estrogen, progesterone and Her2 of the tumor cells. Gene expression profiling of whole breast tumors further stratifies breast cancer into several molecular subtypes which also co-segregate with the receptor status of the tumor cells. We postulated that cancer associated fibroblasts (CAFs within the tumor stroma may exhibit subtype specific gene expression profiles and thus contribute to the biology of the disease in a subtype specific manner. Several studies have reported gene expression profile differences between CAFs and normal breast fibroblasts but in none of these studies were the results stratified based on tumor subtypes. Methods To address whether gene expression in breast cancer associated fibroblasts varies between breast cancer subtypes, we compared the gene expression profiles of early passage primary CAFs isolated from twenty human breast cancer samples representing three main subtypes; seven ER+, seven triple negative (TNBC and six Her2+. Results We observed significant expression differences between CAFs derived from Her2+ breast cancer and CAFs from TNBC and ER + cancers, particularly in pathways associated with cytoskeleton and integrin signaling. In the case of Her2+ breast cancer, the signaling pathways found to be selectively up regulated in CAFs likely contribute to the enhanced migration of breast cancer cells in transwell assays and may contribute to the unfavorable prognosis of Her2+ breast cancer. Conclusions These data demonstrate that in addition to the distinct molecular profiles that characterize the neoplastic cells, CAF gene expression is also differentially regulated in distinct subtypes of breast cancer.
Full Text Available BACKGROUND Breast cancer is the most common malignant tumour in women worldwide. The relationship between breast cancer and thyroid disease is a controversy. Many of the studies showed hypothyroidism as the commonly found thyroid abnormality in breast cancer.  There is considerable evidence for an increased risk of thyroid and breast cancer in patients with iodine deficiency. This ability of iodine to reduce the risk of breast cancer is attributed to the ability of iodine and its compounds to induce apoptosis so that appropriate cell death occurs. Instead, in the absence of optimum level of iodine in the body the transformed cells continue to grow and divide resulting in cancer. AIMS 1. To find out the association of thyroid hormones and breast cancer in early breast cancer patients. 2. To find out the association of thyroid peroxidase antibodies in early breast cancer patients. Settings Cases: 82 breast cancer patients in early stage who attended the breast clinic. Controls: 82 age matched controls (Between 25-80 years. Design: Case control study. MATERIALS AND METHOD In this study, investigated for thyroid function test (T3, T4, TSH and thyroid peroxide antibody level in 82 early breast cancer patients. STATISTICAL ANALYSIS SPSS 16. RESULTS Statistically significant low T4 and high TSH in breast cancer patients, along with elevated thyroid peroxidase antibody. CONCLUSION Compared to hyperthyroidism, hypothyroidism was found to be clinically significant in breast cancer patients
Full Text Available Abstract Background Around 20% of breast cancers (BC show ERBB2 gene amplification and overexpression of the ERBB2 tyrosine kinase receptor. They are associated with a poor prognosis but can benefit from targeted therapy. A better knowledge of these BCs, genomically and biologically heterogeneous, may help understand their behavior and design new therapeutic strategies. Methods We defined the high resolution genome and gene expression profiles of 54 ERBB2-amplified BCs using 244K oligonucleotide array-comparative genomic hybridization and whole-genome DNA microarrays. Expression of ERBB2, phosphorylated ERBB2, EGFR, IGF1R and FOXA1 proteins was assessed by immunohistochemistry to evaluate the functional ERBB2 status and identify co-expressions. Results First, we identified the ERBB2-C17orf37-GRB7 genomic segment as the minimal common 17q12-q21 amplicon, and CRKRS and IKZF3 as the most frequent centromeric and telomeric amplicon borders, respectively. Second, GISTIC analysis identified 17 other genome regions affected by copy number aberration (CNA (amplifications, gains, losses. The expression of 37 genes of these regions was deregulated. Third, two types of heterogeneity were observed in ERBB2-amplified BCs. The genomic profiles of estrogen receptor-postive (ER+ and negative (ER- ERBB2-amplified BCs were different. The WNT/β-catenin signaling pathway was involved in ER- ERBB2-amplified BCs, and PVT1 and TRPS1 were candidate oncogenes associated with ER+ ERBB2-amplified BCs. The size of the ERBB2 amplicon was different in inflammatory (IBC and non-inflammatory BCs. ERBB2-amplified IBCs were characterized by the downregulated and upregulated mRNA expression of ten and two genes in proportion to CNA, respectively. IHC results showed (i a linear relationship between ERBB2 gene amplification and its gene and protein expressions with a good correlation between ERBB2 expression and phosphorylation status; (ii a potential signaling cross-talk between
Full Text Available Background: Triple negative breast cancer (TNBC is a recent concept and the burning topic of research today. Various studies have been reported in western literature on TNBCs or the similar group of basal like cancers, all highlighting the poor prognostic features of this molecular subtype in comparison to the other types of breast cancers. However extensive data from India is lacking. The aim of this study was to analyze the epidemiological and clinical profile of TNBcs at our institute. Materials and Methods: Data on 171 patients of TNBCs registered at this hospital between 2005 and 2008 and followed up until December 2010 was collected and reviewed for epidemiological and clinical features. Results: The median age at presentation was 49 years (22-75 years. Sixty eight patients (40% had lump in the breast of less than 1 month duration. Fourteen (8% were nulliparous and 10 (7% patients had crossed the age of 30 years at first full-term pregnancy, 89 (52% were pre or peri-menopausal at presentation. Only 8 (5% patients had a family history of breast or ovarian cancer. One hundred and six (62% patients were stage II, 26 (15% stage III, 21 (12% stage I and 18 (10% stage IV at presentation. One hundred and twenty eight patients (75% had early breast cancer eligible for surgery at presentation, 25 (15% were locally advanced and received neoadjuvant chemotherapy (NACT and 18 (10% were found to be metastatic. Modified radical mastectomy was the preferred surgical option by most patients (76% who underwent upfront surgery in our study. The pathological overall response rates (complete and partial response after NACT was 75% with complete response rate of 25% and there were no relapses in the complete responders. The median follow-up was 30 months (9-70 months. One hundred and twenty two patients (71% were alive at last follow-up, 34 (22% had relapsed, 18 (11% had died due to progressive disease. Thirty one patients (18% were lost to follow-up. Most of
Jayant D Deshpande , Kailash K Singh , Deepak B Phalke
Full Text Available Background: Cancer is one of the major public health problems worldwide. Prevalence and pattern of cancer is known to vary from region to region. Epidemiological information on cancer including the pattern is an important basis for determining the priorities for cancer control in any population group. Objective: Present work is an attempt to study magnitude, profile and some epidemiological aspects in relation to cancer cases at a tertiary care level teaching hospital in rural area. Method: All records were studied and analyzed. A total of 1106 patients were treated during the period studied. A proforma was used to collect data such as age, sex, place of residence, type of cancers and treatment given. The data collected were entered into MS-Excel sheets and analysis was carried out. The information obtained was tabulated analyzed using the software GraphPad Instat demo version. Results: A total of 1106 cancer patients were treated during the January 2010 to December 2010. Among these, 626(56.60 were females and 480(43.39 were females. In males, the common cancers were oral cavity cancers, lung cancers and GIT cancers. The most common cancers among females were the cervical carcinomas, which constituted 32.10% of the total number of cancers cases followed by cancers of breast. Almost 2/3rd of cases occurred in the age group of 41 to 70 years. Maximum frequency was observed in 51–60 year age group in both sexes. Maximum numbers (74.59% of the cases were from rural area. The main methods of cancer treatment were surgery, chemotherapy and radiotherapy, used alone or in combination. Conclusion: Tobacco and alcohol related cancers predominated in males. In females, cervical cancer predominated over breast cancer. Human behavior is a major determinant in the successful control of cancer. Understanding cancer magnitude, risk and trends will be of help in cancer control.
Ando, Michiyo; Ninosaka, Yasuyoshi; Okamura, Kazuhisa; Ishi, Yoko
The present study aimed to investigate difficulties in caring for a patient with cancer at the end of life at home and to examine relationships between difficulties with care and complicated grief. The 45 bereaved family members completed the Family Difficulty Scale (FDS) and the Inventory of Complicated Grief (ICG). The FDS score for "Patient's pain and condition" was the highest, followed by "Caregivers did not want home care" and "No support from others." There was a significant relationship between FDS and ICG scores. These results suggest that the condition of the patient, the view of the caregiver on home care, and the absence of other support are important factors contributing to difficulties of family caregivers, and that these difficulties may lead to complicated grief.
Full Text Available Abstract 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
profiles have been described in the normal-appearing bronchial epithelium of healthy smokers (9) including those that were diagnostic of lung cancer...expression is modulated in a site- and a time-dependent manner in the bronchial epithelium of early stage lung cancer patients. • Identified several...in airway epithelium and promotes lung inflammation and tumorigenesis. Cancer Prev Res (Phila). 2010;3(4):424-37. PMID: 20354164. 17. Fujimoto J
Full Text Available Background: Caregiving to bedridden patients in India is set to become a major problem in future. Objective: To ascertain the profile of caregivers for the adult bedridden patients in Chandigarh, India. Materials and Methods: This cross-sectional study was conducted on 100 purposively selected bedridden people. The Katz Index of the activities of daily living was used to ascertain their degree of disability. Patients and families were interviewed about the patterns of care provision. Results: The mean age of subjects was 69 years. A majority (68% of them lived in joint families. All of them required assistance in bathing, dressing, toileting, and transfer. In 54% of the cases someone was hired to look after the subjects. A majority of the caregivers (82% were family members. All caregivers were untrained. In 35% of the cases unqualified practitioners were consulted, while in 59% of the cases government hospitals were consulted. Most patients (78 were given medicines on time. Complications like urinary tract infection (39% and pressure ulcers (54% were reported; 57% of the patients reported satisfaction with the care provided. Conclusion: The main source of caregivers for the bedridden was the family. Bedridden people had high rates of medical complications. There is a need for formal training for the caregivers.
Full Text Available Surface enhanced laser desorption/ionization (SELDI time-of-flight mass spectrometry has emerged as a successful tool for serum based detection and differentiation of many cancer types, including breast cancers. In this study, we have applied the SELDI technology to evaluate three potential applications that could extend the effectiveness of established procedures and biomarkers used for prognostication of breast cancers. Paired serum samples obtained from women with breast cancers prior to surgery and post-surgery (6–9 mos. were examined. In 14/16 post-treatment patients, serum protein profiles could be used to distinguish these samples from the pre-treatment cancer samples. When compared to serum samples from normal healthy women, 11 of these post-treatment samples retained global protein profiles not found in healthy women, including five low-mass proteins that remained elevated in both pre-treatment and post-treatment serum groups. In another pilot study, serum profiles were compared for a group of 30 women who were known BRCA-1 mutation carriers, half of whom subsequently developed breast cancer within three years of the sample procurement. SELDI protein profiling accurately classified 13/15 women with BRCA-1 breast cancers from the 15 non-cancer BRCA-1 carriers. Additionally, the ability of SELDI to distinguish between the serum profiles from sentinel lymph node positive and sentinel lymph node negative patients was evaluated. In sentinel lymph node positive samples, 22/27 samples were correctly classified, in comparison to the correct classification of 55/71 sentinel lymph node negative samples. These initial results indicate the utility of protein profiling approaches for developing new diagnostic and prognostic assays for breast cancers.
Full Text Available Aim. Amino acid metabolism in cancer patients differs from that in healthy people. In the study, we performed urine-free amino acid profile of gastric cancer at different stages and health subjects to explore potential biomarkers for diagnosing or screening gastric cancer. Methods. Forty three urine samples were collected from inpatients and healthy adults who were divided into 4 groups. Healthy adults were in group A (n=15, early gastric cancer inpatients in group B (n=7, and advanced gastric cancer inpatients in group C (n=16; in addition, two healthy adults and three advanced gastric cancer inpatients were in group D (n=5 to test models. We performed urine amino acids profile of each group by applying ion chromatography (IC technique and analyzed urine amino acids according to chromatogram of amino acids standard solution. The data we obtained were processed with statistical analysis. A diagnostic model was constructed to discriminate gastric cancer from healthy individuals and another diagnostic model for clinical staging by principal component analysis. Differentiation performance was validated by the area under the curve (AUC of receiver-operating characteristic (ROC curves. Results. The urine-free amino acid profile of gastric cancer patients changed to a certain degree compared with that of healthy adults. Compared with healthy adult group, the levels of valine, isoleucine, and leucine increased (P<0.05, but the levels of histidine and methionine decreased (P<0.05, and aspartate decreased significantly (P<0.01. The urine amino acid profile was also different between early and advanced gastric cancer groups. Compared with early gastric cancer, the levels of isoleucine and valine decreased in advanced gastric cancer (P<0.05. A diagnosis model constructed for gastric cancer with AUC value of 0.936 tested by group D showed that 4 samples could coincide with it. Another diagnosis model for clinical staging with an AUC value of 0.902 tested by
Full Text Available Background: Researchers have reported association of plasma/serum lipids and lipoproteins with different cancers. Increase levels of circulating lipids and lipoproteins have been associated with breast cancer risk. Aim: The aim of this study is to compare serum lipid profiles: total-cholesterol (T-CHOL, triglyceride (TG, high density lipoprotein-cholesterol (HDL-C, low density lipoprotein-cholesterol (LDL-C and very low density lipoprotein-cholesterol (VLDL-C between breast cancer patients and normal participants. Materials and Methods: A total of 403 women in this study were divided into two groups in the period during May 2006-April 2007. Blood samples were collected from 249 patients with early stage breast cancer and 154 normal controls for serum lipid profiles (T-CHOL, TG, HDL-C, LDL-C and VLDL-C analysis using Hitachi 717 Autoanalyzer (Roche Diagnostic GmbH, Germany. TG, LDL-C and VLDL-C levels in breast cancer group were significantly increased as compared with normal controls group (P < 0.001, whereas HDL-C and T-CHOL levels were not. Results: The results of this study suggest that increased serum lipid profiles may associate with breast cancer risk in Thai women. Further studies to group important factors including, cancer stages, types of cancer, parity, and menopausal status that may affect to lipid profiles in breast cancer patients along with an investigation of new lipid profiles to clarify most lipid factors that may involve in breast cancer development are needed.
Holmila, Reetta; Bornholdt, Jette; Suitiala, Tuula
%) frameshift or nonsense mutations, and 36 (23%) intronic or silent mutations. In coding region, the most common base change detected was C-->T transition (43/125; 34% of base changes in the coding region). G-->T transversions occurred at a frequency of 10% (12/125), which is less than reported in mutation...... not been reported before as frequently mutated in head and neck cancer or human cancer in general. About half of all tumours with TP53 mutations carried more than one mutation. Interestingly, 86% (19/22) of the silent mutations detected had occurred in tumours with multiple mutations.......Genetic alterations underlying the development of the cancer of the nose and paranasal sinuses (sinonasal cancer, SNC), a rare cancer that can be included in the group of head and neck cancers, are still largely unknown. We recently reported that TP53 mutations are a common feature of SNC...
Warbhe Priya A, Warbhe Rupesh
Full Text Available Background: Population ageing is a significant product of demographic transition. Declining fertility and improved health and longevity have generated rising proportions of the older population. Double burden of communicable and non-communicable diseases affects the geriatric segment of the population with variable health seeking behaviour. Objectives: To assess morbidity profile, health seeking behaviour and home environmental survey for adaptive measures in geriatric population from an urban community. Material and Methods: Cross-sectional study stratified systematic random sampling was applied. Research tool was interviewer based closed ended questionnaire. Adaptive measures as part of environment survey were assessed. Proportions and Pearson’s chi-square test were calculated. Results: 64.1% participants were from 60-69 years age category, 9.1% current smokers. 94.1% had 1-3 morbidities, 4.1% had 4-6 morbidities .37.3% gave a history of fall and 31.4% history of fracture. 13.6% cataract operation, 16.8% procedure for fracture.10% had dental procedure. 54.2% went to UHC and GOVT/BMC hospitals for treatment and 78.6% received both allopathic and ayurvedic treatment. History of fall was not associated with adaptive measures in the house (p=0.952. Conclusions: Majority of the participants suffered from old age related morbidities, hypertension emerged as a major morbidity. Most of the participants relied on government hospitals for treatment. Adaptive measures were lacking in most of the houses.
Tatiana C.S. Bonetti
Full Text Available PURPOSE: Report the characteristics of cryopreserved semen from a cohort of male cancer patients, attitudes towards cryopreservation and outcomes of semen samples based on a 12-year cryopreservation program. MATERIAL AND METHODS: Data from 98 male cancer patients whose sperm samples were banked were evaluated. Demographic parameters, semen characteristics, destination of sperm banked samples and questionnaires answered by the patients regarding cryopreservation time were evaluated. RESULTS: The cancer diagnoses were testicle (56.1%, prostate (15.3%, Hodgkin’s lymphomas (9.2%, non-Hodgkin’s lymphomas (7.1%, leukemia (3.1% and other malignancies (9.2%. The patients with testicular cancer presented lower sperm concentration (p < 0.001; however, there were no differences with the percentage of normozoospermic patients among cancer type groups (p = 0.185. A shorter time between cancer diagnosis and sperm banking was observed for testicular and prostate cancer patients (p < 0.001. Most of the patients (89.5% favored sperm banking as a fertility preservation method. CONCLUSIONS: Although less than 20% of banked sperm samples were disposed of, the majority of patients related sperm banking with safe for fertility preservation. Our results show that all male cancer patients of reproductive age facing cancer treatment could be offered sperm banking.
Menon, Suraj; Sujatha; Kumar, K. Kalyan; Kurien, Jacob; Krishnanand, B. R.; Mahato, K. K.; George, Sajan D.; Kartha, V. B.; C, Santhosh
Proteomics based techniques are rapidly emerging as alternative techniques to conventional histo-pathological methods for detection and diagnosis of cancers. Tumor markers are of considerable importance in the study of various cancers. A study of various changes in the protein profile associated with breast cancer will facilitate a better understanding of the various dynamic changes associated with the disease. In our study we have used High Performance Liquid Chromatography coupled with highly sensitive Laser Induced Fluorescence for recording the protein profiles of breast tissue homogenates. The protein profiles were recorded from pathologically certified normal as well as malignant breast tissue samples. The recorded protein profiles were studied by using Principal Component Analysis. Good discrimination of normal, benign and malignant samples was achieved in this pilot study.
Full Text Available Wojciech Leppert,1 Mikolaj Majkowicz,2 Maria Forycka,1 Eleonora Mess,3 Agata Zdun-Ryzewska2 1Department of Palliative Medicine, Poznan University of Medical Sciences, Poznan, Poland; 2Department of Quality of Life Research, Gdansk Medical University, Gdansk, Poland; 3Palliative Care Nursing Department, Wroclaw Medical University, Wroclaw, Poland Aim of the study: To assess quality of life (QoL in cancer patients treated at home, at an in-patient palliative care unit (PCU, and at a day care center (DCC. Patients and methods: QoL was assessed in advanced cancer patients at baseline and after 7 days of symptomatic treatment using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 15-Palliative Care (EORTC QLQ-C15-PAL, the Edmonton Symptom Assessment System (ESAS, and the Karnofsky Performance Status (KPS scale. Results: A total of 129 patients completed the study, with 51 patients treated at home, 51 patients treated at the PCU, and 27 patients at DCC. In the EORTC QLQ-C15-PAL, improvement in functional and symptom scales was observed except in physical functioning and fatigue levels; patients at DCC had a better physical functioning, global QoL, appetite, and fatigue levels. In the ESAS, improvement in all items was found except for drowsiness levels, which was stable in patients treated at DCC and deteriorated in home and PCU patients. Higher activity, better appetite and well-being, and less drowsiness were observed in patients treated at DCC. KPS was better in DCC patients compared to those treated at home and at the PCU; the latter group deteriorated. Conclusions: QoL improved in all patient groups, with better results in DCC patients and similar scores in those staying at home and at the PCU. Along with clinical assessment, baseline age, KPS, physical and emotional functioning may be considered when assigning patients to care at a DCC, PCU, or at home. Keywords: oncology, patient care
Palmero, Edenir Inez; Ashton-Prolla, Patricia; da Rocha, José Cláudio C; Vargas, Fernando Regla; Kalakun, Luciane; Blom, Melissa Brauner; Azevedo, Sérgio J; Caleffi, Maira; Giugliani, Roberto; Schüler-Faccini, Lavinia
Hereditary breast cancer (HBC) accounts for 5-10% of breast cancer cases and it significantly increases the lifetime risk of cancer. Our objective was to evaluate the sociodemographic variables, family history of cancer, breast cancer (BC) screening practices and the risk profile of cancer affected or asymptomatic at-risk women that undergo genetic counseling for hereditary breast cancer in public Brazilian cancer genetics services. Estimated lifetime risk of BC was calculated for asymptomatic women using the Gail and Claus models. The majority of women showed a moderate lifetime risk of developing BC, with an average risk of 19.7% and 19.9% by the Gail and Claus models, respectively. The average prior probability of carrying a BRCA1/2 gene mutation was 16.7% and overall only 32% fulfilled criteria for a hereditary breast cancer syndrome as assessed by family history. We conclude that a significant number of individuals at high-risk for HBC syndromes may not have access to the benefits of cancer genetic counseling in these centers. Contributing factors may include insufficient training of healthcare professionals, disinformation of cancer patients; difficult access to genetic testing and/or resistance in seeking such services. The identification and understanding of these barriers is essential to develop specific strategies to effectively achieve cancer risk reduction in this and other countries were clinical cancer genetics is not yet fully established.
Liang, Yuh-Jin; Ding, Yao; Levery, Steven B;
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...... 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...
Adelaide, J.; Finetti, P.; Bekhouche, I.; Repellini, L.; Geneix, J.; Sircoulomb, F.; Charafe-Jauffret, E.; Cervera, N.; Desplans, J.; Parzy, D.; Schoenmakers, E.F.P.M.; Viens, P.; Jacquemier, J.; Birnbaum, D.; Bertucci, F.; Chaffanet, M.
Basal and luminal are two molecular subtypes of breast cancer with opposite histoclinical features. We report a combined, high-resolution analysis of genome copy number and gene expression in primary basal and luminal breast cancers. First, we identified and compared genomic alterations in 45 basal
Background Early diagnosis and timely treatment are important for improving therapeutic efficiency of prostate cancer. DNA array is a new bio-technology for disease diagnosis. This study was conducted to diagnose prostate cancer with cDNA macroarray and analysis gene expression profiles of some selective genes in prostate cancer.Methods Total RNA was isolated from patients with prostate cancer and from normal people, and poly(A) RNA was further purified. Then it was analyzed for differentially expressed genes in prostate cancer and normal prostate by cDNA macroarray system.Results There were different expressions in the nine prostate-associated specific genes in prostate cancer as compared with normal prostate, in which, 7 were significantly upregulated and 2 were down-regulated.Conclusion As a diagnostic approach at molecular level, the cDNA macroarray is an effectively diagnostic method for prostate cancer.
Full Text Available Abstract 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
Bentur, Netta; Resnizky, Shirli; Balicer, Ran; Eilat-Tsanani, Tsofia
This study examined the utilization and cost of all health services consumed during the last six months of life by cancer patients, and compared those with and without home-hospice care. Detailed information was extracted from the health care electronic administrative data files on 193 deceased cancer patients that their family approved the study (out of 429, 45%). About 88% had been hospitalized for 19 days on average and 53% visited the ER. One quarter received home-hospice care. Their average cost was $13,648 compared to $18,503 for patients without home-hospice care. Hospitalization contributed 32% to the total cost of patients with home-hospice care and 64% for those with it. The findings support the justification for significant expansion of home-hospice care.
Ehab, Moataz; Elbaz, Mohamad
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
Full Text Available Abstract Background Matrix-assisted laser desorption/ionization (MALDI mass spectrometry (MS has been demonstrated to be useful for molecular profiling of common solid tumors. Using recently developed MALDI matrices for lipid profiling, we evaluated whether direct tissue MALDI MS analysis on proteins and lipids may classify human breast cancer samples according to the intrinsic subtype. Methods Thirty-four pairs of frozen, resected breast cancer and adjacent normal tissue samples were analyzed using histology-directed, MALDI MS analysis. Sinapinic acid and 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument. Results Protein and lipid profiles distinguish cancer from adjacent normal tissue samples with the median prediction accuracy of 94.1%. Luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by permutation P values less than 0.01 for 0.632+ bootstrap cross-validated misclassification rates with all classifiers tested. Discriminatory proteins and lipids were useful for classifying tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in random test sets. Conclusions Protein and lipid profiles accurately distinguish tumor from adjacent normal tissue and classify breast cancers according to the intrinsic subtype.
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
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.
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.
Full Text Available Moataz Ehab,1 Mohamad Elbaz2,31Department of Pharmacy Practice, 2Department of Pharmacology, Pharmacy School, Helwan University, Egypt; 3Department of Pathology, The Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH, USAAbstract: 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
Yoon, Joon Kee; Lee, Myung Hoon; Joh, Chul Woo; Yoon, Seok Nam; Soh, Eui Young [College of Medicine, Univ. of Ajou, Suwon (Korea, Republic of)
Low sensitivity of diagnostic whole body iodine scintigraphy and intermediate range of serum thyroglobulin (Tg) with or without anti-Tg antibody make it difficult to select the patients with differentiated thyroid cancer who need further treatment. Surfaced Enhanced Laser Desorption /Ionization - Time of Flight - Mass Spectrometry (SELDI TOF MS) is a useful method to evaluate cancer proteome, biomarkers and patterns of biomarkers. In this preliminary study, we evaluated and developed protein profiles for the discrimination between patients with differentiated thyroid cancer and non-cancer controls using SELDI technology. Serum samples from 10 healthy controls and from 14 patients with papillary thyroid cancer before thyroidectomy were analyzed by SELDI MS. Multiple protein peaks detected were analyzed by the computer software to develop a classifier for separating cancer patients form controls. The classifier was then challenged to 24 serum samples to determine the validity and accuracy of the classification system. All patients with papillary thyroid cancer had no other concomitant cancer or thyroiditis. Their serum Tg concentration was 55.8 (1.5 - 249.7) and 2 patients had extra-thyroidal extension. According to the SELDI analysis, protein peaks at 3696 Da, 4178 Da, and 8149 Da were more prominent in cancer patients than controls in various degrees. Among those, protein peak at 4178 Da was determined as classifier by computer software, and the sensitivity, specificity and accuracy for discrimination of cancer patients from controls was 92.9% (13/14), 90% (9/10) and 91.7% respectively. This preliminary study suggests that serum protein profiles of differentiated thyroid cancer can be used for differentiation between cancer patients and non-cancer controls. And further clinical studies in various test sets will offer useful information in selecting patients who require treatment.
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
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.
Callesen, Anne Kjærgaard; Vach, Werner; Jørgensen, Per E;
Serum protein profiling by mass spectrometry has achieved attention as a promising technology in oncoproteomics. We performed a systematic review of published reports on protein profiling as a diagnostic tool for breast cancer. The MEDLINE, EMBASE, and COCHRANE databases were searched for original...... studies reporting discriminatory protein peaks for breast cancer as either protein identity or as m/ z values in the period from January 1995 to October 2006. To address the important aspect of reproducibility of mass spectrometry data across different clinical studies, we compared the published lists....... Although the studies revealed a considerable heterogeneity in relation to experimental design, biological variation, preanalytical conditions, methods of computational data analysis, and analytical reproducibility of profiles, we found that 45% of peaks previously reported to correlate with breast cancer...
Corrêa, Natássia C R; Kuasne, Hellen; Faria, Jerusa A Q A
Breast cancer is the most common type of cancer among women worldwide. Research using breast cancer cell lines derived from primary tumors may provide valuable additional knowledge regarding this type of cancer. Therefore, the aim of this study was to investigate the phenotypic profiles of MACL-1...... and MGSO-3, the only Brazilian breast cancer cell lines available for comparative studies. We evaluated the presence of hormone receptors, proliferation, differentiation and stem cell markers, using immunohistochemical staining of the primary tumor, cultured cells and xenografts implanted....... This shift in expression may be due to the selection of an 'establishment' phenotype in vitro. Whole-genome DNA evaluation showed a large amount of copy number alterations (CNAs) in the two cell lines. These findings render MACL-1 and MGSO-3 the first characterized Brazilian breast cancer cell lines...
Tsang Percy CK
.7% (DAPK in cervical cancer. Aberrant methylation for some genes (BRCA1, DAPK, hMLH1, MGMT, p14, p16, and PTEN was also associated with clinico-pathological data. Conclusion Thus, differential methylation profiles occur in the three types of gynecologic cancer. Detection of methylation for critical loci is potentially useful as epigenetic markers in tumor classification. More studies using a much larger sample size are needed to define the potential role of DNA methylation as marker for cancer management.
Full Text Available 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.
Øgendahl Callesen, Anne Kjærgaard; Mogensen, Ole; Jensen, Andreas K;
The focus of this systematic review is to give an overview of the current status of clinical protein profiling studies using MALDI and SELDI MS platforms in the search for ovarian cancer biomarkers. A total of 34 profiling studies were qualified for inclusion in the review. Comparative analysis......, and data analysis. About 47% of the peaks reported to be associated to ovarian cancer were also represented in our experimental study, and 34% of these redetected peaks also showed a significant difference between cases and controls in our study. Thus, despite known problems related to reproducibility...... an overlap in peaks between clinical studies was demonstrated, which indicate convergence toward a set of common discriminating, reproducible peaks for ovarian cancer. The potential of the discriminating protein peaks for clinical use as ovarian cancer biomarkers will be discussed and evaluated. This article...
Thomassen, Mads; Tan, Qihua; Eiriksdottir, Freyja;
Promising results for prediction of outcome in breast cancer have been obtained by genome wide gene expression profiling. Some studies have suggested that an extensive overtreatment of breast cancer patients might be reduced by risk assessment with gene expression profiling. A patient group hardly...... examined in these studies is the low-risk patients for whom outcome is very difficult to predict with currently used methods. These patients do not receive adjuvant treatment according to the guidelines of the Danish Breast Cancer Cooperative Group (DBCG). In this study, 26 tumors from low-risk patients...... demonstrated high cross-platform consistency of the classifiers. Higher performance of HUMAC32 was demonstrated among the low-malignant cancers compared with the 70-gene classifier. This suggests that although the metastatic potential to some extend is determined by the same genes in groups of tumors...
Erci, Behice; Özdemir, Süreyya
Despite many researches that have examined life attitude profile, treatment decision evaluation, and symptoms experienced in cancer populations, the relationships between life attitude profile and symptoms experienced with treatment decision evaluation are still not well understood. A thorough understanding of these relationships is critical for health care professionals to provide appropriate management to patients. The aim of this study was to determine relationships among life attitude profile, the treatment decision evaluation, and symptoms experienced in Turkish patients with cancer. A convenience sample of 199 patients with cancer at a Turkish university hospital completed a structured questionnaire including demographic characteristics and the Life Attitude Profile-Revised Scale for patients with cancer in 2007. The researchers visited the oncology clinic 5 work days every week and conducted interviews with the patients. The life attitude profile was not correlated with the treatment decision evaluation and symptoms experienced (r = 0.082, r = -026). The treatment decision evaluation showed that the patients were uncertain about their satisfaction with the treatment decision. Significant correlations were found between the treatment decision evaluation and symptoms experienced (r = 0.206; P <.01). Holistic nursing interventions can be implemented as they promote healing of the whole person processes as facilitating self-awareness, living meaningfully, and promotion connection with others and with nature and a higher power.
Thomassen, Mads; Tan, Qihua; Eiriksdottir, Freyja;
-six tumors from low-risk patients and 34 low-malignant T2 tumors from patients with slightly higher risk have been examined by genome-wide gene expression analysis. Nine prognostic gene sets were tested in this data set. RESULTS: A 32-gene profile (HUMAC32) that accurately predicts metastasis has previously...... sets, mainly developed in high-risk cancers, predict metastasis from low-malignant cancer....
In this study, protein profiling was performed on gastric cancer tissue samples in order to identify proteins that could be utilized for an effective diagnosis of this highly heterogeneous disease and as targets for therapeutic approaches. To this end, 16 pairs of postoperative gastric adenocarcinomas and adjacent non-cancerous control tissues were analyzed on microarrays that contain 813 antibodies targeting 724 proteins. Only 17 proteins were found to be differentially regulated, with much ...
Charles F. Streckfus
Full Text Available Purpose. The objective of this study was to compare the salivary protein profiles from individuals diagnosed with breast cancer that were either HER2/neu receptor positive or negative. Methods. Two pooled saliva specimens underwent proteomic analysis. One pooled specimen was from women diagnosed with stage IIa HER2/neu-receptor-positive breast cancer patients (n=10 and the other was from women diagnosed with stage IIa HER2/neu-receptor-negative cancer patients (n=10. The pooled samples were trypsinized and the peptides labeled with iTRAQ reagent. Specimens were analyzed using an LC-MS/MS mass spectrometer. Results. The results yielded approximately 71 differentially expressed proteins in the saliva specimens. There were 34 upregulated proteins and 37 downregulated proteins.
Full Text Available MicroRNAs (miRNAs are a class of small, non-coding RNA molecules that can regulate gene expression, thereby affecting crucial processes in cancer development. miRNAs offer great potential as biomarkers for cancer detection because of their remarkable stability in blood and their characteristic expression in different diseases. We investigated whether quantitative RT-PCR miRNA profiling on serum could discriminate between breast cancer patients and healthy controls. We performed miRNA profiling on serum from breast cancer patients, followed by construction of ROC (Receiver Operating Characteristic curves to determine the sensitivity and specificity of the assay. We found that seven miRNAs (miR-10b, miR-21, miR-125b, miR-145, miR-155 miR-191 and miR-382 had different expression patterns in serum of breast cancer patients compared to healthy controls. ROC curve analyses revealed that three serum miRNAs could be valuable biomarkers for distinguishing BC from normal controls. Additionally, a combination of ROC curve analyses of miR-145, miR-155 and miR-382 showed better sensitivity and specificity of our assay. miRNA profiling in serum has potential as a novel method for breast cancer detection in the Mexican population.
Veer, L.J. van 't; Dai, H.; Vijver, H. van de; He, Y.D.; Hart, A.A.M.; Mao, M.; Peterse, H.L.; Kooy, K. van der; Marton, M.J.; Witteveen, A.T.; Schreiber, G.J.; Kerkhoven, R.M.; Roberts, C.; Linsley, P.S.; Bernards, R.A.; Friend, S.H.
Breast cancer patients with the same stage of disease can have markedly different treatment responses and overall outcome. The strongest predictors for metastases (for example, lymph node status and histological grade) fail to classify accurately breast tumours according to their clinical behaviour.
Thorsteinsson, Morten; Kirkeby, Lene T; Hansen, Raino;
were retrieved from the Gene Expression Omnibus (GEO) (n¿=¿111) in addition to a Danish data set (n¿=¿37). All patients had stages II and III colon cancers. A Prediction Analysis of Microarray classifier, based on the 128-gene signature and the original training set of stage I (n¿=¿65) and stage IV (n......¿=¿76) colon cancers, was reproduced. The stages II and III colon cancers were subsequently classified as either stage I-like (good prognosis) or stage IV-like (poor prognosis) and assessed by the 36 months cumulative incidence of relapse. RESULTS: In the GEO data set, results were reproducible in stage...... correctly predicted as stage IV-like, and the remaining patients were predicted as stage I-like and unclassifiable, respectively. Stage II patients could not be stratified. CONCLUSIONS: The 128-gene signature showed reproducibility in stage III colon cancer, but could not predict recurrence in stage II...
Full Text Available Research on molecular mechanisms of carcinogenesis plays an important role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to non-invasively identify the potential biomarkers for the early diagnosis of human gastric cancer. The aims of this study were to explore the underlying metabolic mechanisms of gastric cancer and to identify biomarkers associated with morbidity. Gas chromatography/mass spectrometry (GC/MS was used to analyze the serum metabolites of 30 Chinese gastric cancer patients and 30 healthy controls. Diagnostic models for gastric cancer were constructed using orthogonal partial least squares discriminant analysis (OPLS-DA. Acquired metabolomic data were analyzed by the nonparametric Wilcoxon test to find serum metabolic biomarkers for gastric cancer. The OPLS-DA model showed adequate discrimination between cancer and non-cancer cohorts while the model failed to discriminate different pathological stages (I-IV of gastric cancer patients. A total of 44 endogenous metabolites such as amino acids, organic acids, carbohydrates, fatty acids, and steroids were detected, of which 18 differential metabolites were identified with significant differences. A total of 13 variables were obtained for their greatest contribution in the discriminating OPLS-DA model [variable importance in the projection (VIP value >1.0], among which 11 metabolites were identified using both VIP values (VIP >1 and the Wilcoxon test. These metabolites potentially revealed perturbations of glycolysis and of amino acid, fatty acid, cholesterol, and nucleotide metabolism of gastric cancer patients. These results suggest that gastric cancer serum metabolic profiling has great potential in detecting this disease and helping to understand its metabolic mechanisms.
The incidence of thyroid cancer is increasing worldwide and thyroid nodules are a frequent clinical finding. Diagnosing follicular cell-derived cancers is, however, challenging both histopathologically and especially cytopathologically. The advent of high-throughput molecular technologies has...... profiling of follicular cell-derived thyroid cancers....... prompted many researchers to explore the transcriptome and, in recent years, also the miRNome in order to generate new molecular classifiers capable of classifying thyroid tumours more accurately than by conventional cytopathological and histopathological methods. This has led to a number of molecular...
Wallin, A; Francis, P; Nilbert, M;
the incidence in fact has increased. To improve chemotherapy and enable personalised treatment, the need of biomarkers is of great significance. In this study, we evaluated the gene expression profiles of the colon cancer cell lines treated with SN-38, the active metabolite of topoisomerase-1 inhibitor......Colorectal cancer is the third most common form of cancer in the industrial countries. Due to advances regarding the treatments, primarily development of improved surgical methods and the ability to make the earlier diagnosis, the mortality has remained constant during the past decades even though...
Wilhelm-Benartzi, C S; Koestler, D C; Houseman, E A; Christensen, B C; Wiencke, John K; Schned, A R; Karagas, M R; Kelsey, K T; Marsit, C J
DNA methylation profiles can be used to define molecular cancer subtypes that may better inform disease etiology and clinical decision-making. This investigation aimed to create DNA methylation profiles of bladder cancer based on CpG methylation from almost 800 cancer-related genes and to then examine the relationship of those profiles with exposures related to risk and clinical characteristics. DNA, derived from formalin-fixed paraffin-embedded tumor samples obtained from incident cases involved in a population-based case-control study of bladder cancer in New Hampshire, was used for methylation profiling on the Illumina GoldenGate Methylation Bead Array. Unsupervised clustering of those loci with the greatest change in methylation between tumor and non-diseased tissue was performed to defined molecular subgroups of disease, and univariate tests of association followed by multinomial logistic regression was used to examine the association between these classes, bladder cancer risk factors and clinical phenotypes. Membership in the two most methylated classes was significantly associated with invasive disease (P class 3 and 4). Male gender (P = 0.04) and age >70 years (P = 0.05) was associated with membership in one of the most methylated classes. Finally, average water arsenic levels in the highest percentile predicted membership in an intermediately methylated class of tumors (P = 0.02 for both classes). Exposures and demographic associated with increased risk of bladder cancer specifically associate with particular subgroups of tumors defined by DNA methylation profiling and these subgroups may define more aggressive disease.
OSAWA, SOSHI; Shimada, Yutaka; Sekine, Shinichi; Okumura, Tomoyuki; Nagata, Takuya; Fukuoka, Junya; TSUKADA, kazuhiro
MicroRNA (miRNA) is a small non-coding RNA that targets specific mRNA. Recent progress in the extraction of RNA from formalin-fixed paraffin-embedded (FFPE) tissues has facilitated miRNA profiling using samples stored in laboratories worldwide. In the present study, miRNA profiling of gastric cancer patients is determined using FFPE samples. First, criteria were established for determining evaluable RNA from the FFPE samples. miRNA profiling was then undertaken using miRNA oligo chips with 88...
Xiao, Yongsheng; Guo, Lei; Wang, Yinsheng
Kinases are among the most intensively pursued enzyme superfamilies as targets for anti-cancer drugs. Large data sets on inhibitor potency and selectivity for more than 400 human kinases became available recently, offering the opportunity to design rationally novel kinase-based anti-cancer therapies. However, the expression levels and activities of kinases are highly heterogeneous among different types of cancer and even among different stages of the same cancer. The lack of effective strategy for profiling the global kinome hampers the development of kinase-targeted cancer chemotherapy. Here, we introduced a novel global kinome profiling method, based on our recently developed isotope-coded ATP-affinity probe and a targeted proteomic method using multiple-reaction monitoring (MRM), for assessing simultaneously the expression of more than 300 kinases in human cells and tissues. This MRM-based assay displayed much better sensitivity, reproducibility, and accuracy than the discovery-based shotgun proteomic method. Approximately 250 kinases could be routinely detected in the lysate of a single cell line. Additionally, the incorporation of iRT into MRM kinome library rendered our MRM kinome assay easily transferrable across different instrument platforms and laboratories. We further employed this approach for profiling kinase expression in two melanoma cell lines, which revealed substantial kinome reprogramming during cancer progression and demonstrated an excellent correlation between the anti-proliferative effects of kinase inhibitors and the expression levels of their target kinases. Therefore, this facile and accurate kinome profiling assay, together with the kinome-inhibitor interaction map, could provide invaluable knowledge to predict the effectiveness of kinase inhibitor drugs and offer the opportunity for individualized cancer chemotherapy.
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
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.
Full Text Available Cancer represents a major public health and economical burden in developed countries and has emerged as a major public health problem in developing countries, matching its effect in industrialized nations. Although there have been recent declines in breast cancer mortality rates in some European Union countries, breast cancer remains of key importance to public health in Europe. Now days there is increasing recognition of the causative role of lifestyle factors, as smoking, diet, alcohol consumption, or lake of physical activity. The present study aimed to appreciate the presence and magnitude of modifiable risk factors for breast cancer in a sample of patients diagnosed with the disease, and to outline a risk profile liable to be changed in the intention of reducing the global risk. Risk factors have been investigated in 65 patients diagnosed with breast cancer using a questionnaire for breast cancer risk factors evaluation. The high risk profile was identified as taking shape for urban environment, modulated by the impact of overweight-obesity, smoking, reproductive factors and environmental exposure to different chemical substances. From the public health perspective, the control of overweight and obesity comes out in the foreground of preventive activities. Public health approaches emphasize on inexpensive, practical methods and in this perspective the approach of obesity should focus on the alteration of environmental context, promoting healthy eating and increased physical activity which could have a positive, independent impact on breast cancer risk
Wang, Zhigang C; Lin, Ming; Wei, Lee-Jen; Li, Cheng; Miron, Alexander; Lodeiro, Gabriella; Harris, Lyndsay; Ramaswamy, Sridhar; Tanenbaum, David M; Meyerson, Matthew; Iglehart, James D; Richardson, Andrea
Gene expression array profiles identify subclasses of breast cancers with different clinical outcomes and different molecular features. The present study attempted to correlate genomic alterations (loss of heterozygosity; LOH) with subclasses of breast cancers having distinct gene expression signatures. Hierarchical clustering of expression array data from 89 invasive breast cancers identified four major expression subclasses. Thirty-four of these cases representative of the four subclasses were microdissected and allelotyped using genome-wide single nucleotide polymorphism detection arrays (Affymetrix, Inc.). LOH was determined by comparing tumor and normal single nucleotide polymorphism allelotypes. A newly developed statistical tool was used to determine the chromosomal regions of frequent LOH. We found that breast cancers were highly heterogeneous, with the proportion of LOH ranging widely from 0.3% to >60% of heterozygous markers. The most common sites of LOH were on 17p, 17q, 16q, 11q, and 14q, sites reported in previous LOH studies. Signature LOH events were discovered in certain expression subclasses. Unique regions of LOH on 5q and 4p marked a subclass of breast cancers with "basal-like" expression profiles, distinct from other subclasses. LOH on 1p and 16q occurred preferentially in a subclass of estrogen receptor-positive breast cancers. Finding unique LOH patterns in different groups of breast cancer, in part defined by expression signatures, adds confidence to newer schemes of molecular classification. Furthermore, exclusive association between biological subclasses and restricted LOH events provides rationale to search for targeted genes.
Full Text Available Abstract Background To globally characterize the cancer stroma expression profile of muscle-invasive transitional cell carcinoma and to discuss the cancer biology as well as biomarker discovery from stroma. Laser capture micro dissection was used to harvest purified muscle-invasive bladder cancer stromal cells and normal urothelial stromal cells from 4 paired samples. Two-dimensional liquid chromatography tandem mass spectrometry was used to identify the proteome expression profile. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature. Results We identified 868/872 commonly expressed proteins and 978 differential proteins from 4 paired cancer and normal stromal samples using laser capture micro dissection coupled with two-dimensional liquid chromatography tandem mass spectrometry. 487/491 proteins uniquely expressed in cancer/normal stroma. Differential proteins were compared with the entire list of the international protein index (IPI, and there were 42/42 gene ontology (GO terms exhibited as enriched and 8/5 exhibited as depleted in cellular Component, respectively. Significantly altered pathways between cancer/normal stroma mainly include metabolic pathways, ribosome, focal adhesion, etc. Finally, descriptive statistics show that the stromal proteins with extremes of PI and MW have the same probability to be a biomarker. Conclusions Based on our results, stromal cells are essential component of the cancer, biomarker discovery and network based multi target therapy should consider neoplastic cells itself and corresponding stroma as whole one.
Full Text Available Introduction & Objective: This study compared the personality profile of cancer patients with that of normal persons. The aim was identifying personality traits related to people who suffered from cancer, and helping them to cope with the situation and adjust with life.Materials & Methods: This research was a casual comparative study. For this purpose 100 persons were selected from hematology and oncology center and asked to complete (NEO personality inventory. Then 94 persons were selected as matched group. Results: The result showed that neuroticism was high in cancer patients (p<0.00. Also there were significant differences between normal people and cancer patients in adaptibility and extroversion with high scores in normal people (p<0.05. But there were no significant difference between the two groups in agreeableness and conscientious.Conclusion: In general the result of this research demonstrated that the cancer patients were more neurotic and less adaptable and extrovert therefore they need psychotherapy.
Kim, Young S; Milner, John A
Cancer cells possess unique metabolic signatures compared to normal cells, including shifts in aerobic glycolysis, glutaminolysis, and de novo biosynthesis of macromolecules. Targeting these changes with agents (drugs and dietary components) has been employed as strategies to reduce the complications associated with tumorigenesis. This paper highlights the ability of several food components to suppress tumor-specific metabolic pathways, including increased expression of glucose transporters, oncogenic tyrosine kinase, tumor-specific M2-type pyruvate kinase, and fatty acid synthase, and the detection of such effects using various metabonomic technologies, including liquid chromatography/mass spectrometry (LC/MS) and stable isotope-labeled MS. Stable isotope-mediated tracing technologies offer exciting opportunities for defining specific target(s) for food components. Exposures, especially during the early transition phase from normal to cancer, are critical for the translation of knowledge about food components into effective prevention strategies. Although appropriate dietary exposures needed to alter cellular metabolism remain inconsistent and/or ill-defined, validated metabonomic biomarkers for dietary components hold promise for establishing effective strategies for cancer prevention.
Full Text Available 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.
Nordahl, Helene; Hvidtfeldt, Ulla Arthur; Diderichsen, Finn; Rod, Naja Hulvej; Osler, Merete; Frederiksen, Birgitte Lidegaard; Prescott, Eva; Tjønneland, Anne; Lange, Theis; Keiding, Niels; Andersen, Per Kragh; Andersen, Ingelise
The Social Inequality in Cancer (SIC) cohort study was established to determine pathways through which socioeconomic position affects morbidity and mortality, in particular common subtypes of cancer. Data from seven well-established cohort studies from Denmark were pooled. Combining these cohorts provided a unique opportunity to generate a large study population with long follow-up and sufficient statistical power to develop and apply new methods for quantification of the two basic mechanisms underlying social inequalities in cancer-mediation and interaction. The SIC cohort included 83 006 participants aged 20-98 years at baseline. A wide range of behavioural and biological risk factors such as smoking, physical inactivity, alcohol intake, hormone replacement therapy, body mass index, blood pressure and serum cholesterol were assessed by self-administered questionnaires, physical examinations and blood samples. All participants were followed up in nationwide demographic and healthcare registries. For those interested in collaboration, further details can be obtained by contacting the Steering Committee at the Department of Public Health, University of Copenhagen, at firstname.lastname@example.org.
Young S. Kim
Full Text Available Cancer cells possess unique metabolic signatures compared to normal cells, including shifts in aerobic glycolysis, glutaminolysis, and de novo biosynthesis of macromolecules. Targeting these changes with agents (drugs and dietary components has been employed as strategies to reduce the complications associated with tumorigenesis. This paper highlights the ability of several food components to suppress tumor-specific metabolic pathways, including increased expression of glucose transporters, oncogenic tyrosine kinase, tumor-specific M2-type pyruvate kinase, and fatty acid synthase, and the detection of such effects using various metabonomic technologies, including liquid chromatography/mass spectrometry (LC/MS and stable isotope-labeled MS. Stable isotope-mediated tracing technologies offer exciting opportunities for defining specific target(s for food components. Exposures, especially during the early transition phase from normal to cancer, are critical for the translation of knowledge about food components into effective prevention strategies. Although appropriate dietary exposures needed to alter cellular metabolism remain inconsistent and/or ill-defined, validated metabonomic biomarkers for dietary components hold promise for establishing effective strategies for cancer prevention.
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.
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
Hui-Hua Lee, Chu-Ai Lim, Yew-Teik Cheong, Manjit Singh, Lay-Harn Gam
Full Text Available Breast cancer is the most common cancer among women worldwide. Breast cancer metastasis primarily happens through lymphatic system, where the extent of lymph node metastasis is the major factor influencing staging, prognosis and therapeutic decision of the disease. We aimed to study the protein expression changes in different N (regional lymph nodes stages of breast cancer. Protein expression profiles of breast cancerous and adjacent normal tissues were mapped by proteomics approach that comprises of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE and tandem mass spectrometry (LC-MS/MS analysis. Calreticulin and tropomyosin alpha 3 chains were the common up-regulated proteins in N0, N1 and N2 stages of breast cancer. Potential biomarker for each N stage was HSP 70 for N0, 80 k protein H precursor and PDI for N1 stage while 78 kDa glucose-regulated protein was found useful for N2 stage. In addition, significant up-regulation of PDI A3 was detected only in the metastasized breast cancer. The up-regulation expression of these proteins in cancerous tissues can potentially use as indicators for diagnosis, treatment and prognosis of different N stages of breast cancer.
The emergence of a huge volume of "omics" data enables a computational approach to the investigation of the biology of cancer.The cancer informatics approach is a useful supplement to the traditional experimental approach.I reviewed several reports that used a bioinformatics approach to analyze the associations among aging,stem cells,and cancer by microarray gene expression profiling.The high expression of aging-or human embryonic stem cell-related molecules in cancer suggests that certain important mechanisms are commonly underlying aging,stem cells,and cancer.These mechanisms are involved in cell cycle regulation,metabolic process,DNA damage response,apoptosis,p53 signaling pathway,immune/inflammatory response,and other processes,suggesting that cancer is a developmental and evolutional disease that is strongly related to aging.Moreover,these mechanisms demonstrate that the initiation,proliferation,and metastasis of cancer are associated with the deregulation of stem cells.These findings provide insights into the biology of cancer.Certainly,the findings that are obtained by the informatics approach should be justified by experimental validation.This review also noted that next-generation sequencing data provide enriched sources for cancer informatics study.
The emergence of a huge volume of "omics" data enables a computational approach to the investigation of the biology of cancer. The cancer informatics approach is a useful supplement to the traditional experimental approach. I reviewed several reports that used a bioinformatics approach to analyze the associations among aging, stem cells, and cancer by microarray gene expression profiling. The high expression of aging- or human embryonic stem cell-related molecules in cancer suggests that certain important mechanisms are commonly underlying aging, stem cells, and cancer. These mechanisms are involved in cell cycle regulation, metabolic process, DNA damage response, apoptosis, p53 signaling pathway, immune/inflammatory response, and other processes, suggesting that cancer is a developmental and evolutional disease that is strongly related to aging. Moreover, these mechanisms demonstrate that the initiation, proliferation, and metastasis of cancer are associated with the deregulation of stem cells. These findings provide insights into the biology of cancer. Certainly, the findings that are obtained by the informatics approach should be justified by experimental validation. This review also noted that next-generation sequencing data provide enriched sources for cancer informatics study.
Isinger-Ekstrand, Anna; Johansson, Jan; Ohlsson, Mattias
We aimed to characterize the genomic profiles of adenocarcinomas in the gastroesophageal junction in relation to cancers in the esophagus and the stomach. Profiles of gains/losses as well as gene expression profiles were obtained from 27 gastroesophageal adenocarcinomas by means of 32k high......15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction, with upregulation in one quarter of the tumors. Gains....../losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can...
Wang, Kai; Yuen, Siu Tsan; Xu, Jiangchun; Lee, Siu Po; Yan, Helen H N; Shi, Stephanie T; Siu, Hoi Cheong; Deng, Shibing; Chu, Kent Man; Law, Simon; Chan, Kok Hoe; Chan, Annie S Y; Tsui, Wai Yin; Ho, Siu Lun; Chan, Anthony K W; Man, Jonathan L K; Foglizzo, Valentina; Ng, Man Kin; Chan, April S; Ching, Yick Pang; Cheng, Grace H W; Xie, Tao; Fernandez, Julio; Li, Vivian S W; Clevers, Hans; Rejto, Paul A; Mao, Mao; Leung, Suet Yi
Gastric cancer is a heterogeneous disease with diverse molecular and histological subtypes. We performed whole-genome sequencing in 100 tumor-normal pairs, along with DNA copy number, gene expression and methylation profiling, for integrative genomic analysis. We found subtype-specific genetic and e
Li, Qiyuan; Eklund, Aron Charles; Birkbak, Nicolai Juul;
BACKGROUND: Genome scale expression profiling of human tumor samples is likely to yield improved cancer treatment decisions. However, identification of clinically predictive or prognostic classifiers can be challenging when a large number of genes are measured in a small number of tumors. RESULTS...
Full Text Available Background: Gain of the q arm of chromosome 20 in human colorectal cancer has been associated with poorer survival time and has been reported to increase in frequency from adenomas to metastasis. The increasing frequency of chromosome 20q amplification during colorectal cancer progression and the presence of this amplification in carcinomas of other tissue origin has lead us to hypothesize that 20q11-13 harbors one or more genes which, when over expressed promote tumor invasion and metastasis. Aims: Generate genomic and expression profiles of the 20q amplicon in human cancer cell lines in order to identify genes with increased copy number and expression. Materials and Methods: Utilizing genomic sequencing clones and amplification mapping data from our lab and other previous studies, BAC/ PAC tiling paths spanning the 20q amplicon and genomic microarrays were generated. Array-CGH on the custom array with human cancer cell line DNAs was performed to generate genomic profiles of the amplicon. Expression array analysis with RNA from these cell lines using commercial oligo microarrays generated expression profiles of the amplicon. The data were then combined in order to identify genes with increased copy number and expression. Results: Over expressed genes in regions of increased copy number were identified and a list of potential novel genetic tumor markers was assembled based on biological functions of these genes Conclusions: Performing high-resolution genomic microarray profiling in conjunction with expression analysis is an effective approach to identify potential tumor markers.
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
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.
A.N.A. Milne; R. Carvalho; F.M. Morsink; A.R. Musler; W.W.J. de Leng; A. Ristimaki; G.J.A. Offerhaus
Many studies examine the molecular genetics of gastric cancer, but few look at young patients in particular and there is no comparison of molecular expression between early-onset gastric cancer (<= 45 years old) and conventional gastric cancers. Expression of cycloxygenase-2 (COX-2) is elevated in g
Full Text Available 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.
Full Text Available Abstract Global analysis of gene expression by DNA microarrays is nowadays a widely used tool, especially relevant for cancer research. It helps the understanding of complex biology of cancer tissue, allows identification of novel molecular markers, reveals previously unknown molecular subtypes of cancer that differ by clinical features like drug susceptibility or general prognosis. Our aim was to compare gene expression profiles in breast cancer that develop against a background of inherited predisposing mutations versus sporadic breast cancer. In this preliminary study we analysed seven hereditary, BRCA1 mutation-linked breast cancer tissues and seven sporadic cases that were carefully matched by histopathology and ER status. Additionally, we analysed 6 samples of normal breast tissue. We found that while the difference in gene expression profiles between tumour tissue and normal breast can be easily recognized by unsupervised algorithms, the difference between those two types of tumours is more discrete. However, by supervised methods of data analysis, we were able to select a set of genes that may differentiate between hereditary and sporadic tumours. The most significant difference concerns genes that code for proteins engaged in regulation of transcription, cellular metabolism, signalling, proliferation and cell death. Microarray results for chosen genes (TOB1, SEPHS2 were validated by real-time RT-PCR.
Daniella Reis Barbosa Martelli
Full Text Available Internação domiciliar é uma modalidade de atendimento à saúde que está se transformando em uma alternativa importante para minimizar alguns dos principais problemas inerentes aos sistemas de saúde vigentes, especialmente os da rede pública. O objetivo do estudo foi descrever o perfil sociodemográfico e clínico da população assistida pelo Programa de Internação Domiciliar (PID HU em Casa do Hospital Universitário Clemente de Faria da Universidade Estadual de Montes Claros. O estudo foi descritivo e retrospectivo por meio da análise de prontuários, realizada de maio de 2005 a maio de 2008. Foram analisados 137 pacientes, sendo 75 do gênero feminino (54,7% e 62 do masculino (45,3%. O grupo de 61 a 80 anos foi mais prevalente (37,2% e 73% dos pacientes residiam em bairros periféricos do município de Montes Claros-MG. Dos agravos mais comuns na primeira internação, a pneumonia foi prevalente, 22 casos (16,1%. A maioria dos pacientes foi encaminhada ao PID pela clinica médica (84,7%, com intervalo de maior prevalência de duas a três internações (42,4%. Do total de pacientes, 120 (87,6% permaneceram internados por 16 a 30 dias e 51,8% não necessitaram passar novamente pelo PID para uma segunda internação. Com relação à resolutividade clínica, 130 (94,9% tiveram alta clínica, no PID, na primeira internação. O PID mostrou-se ser um programa de alta resolutividade, atendendo mais ao público idoso feminino, de baixa renda e com períodos de internação relativamente curtos.The home care is a modality of health care which is becoming an important alternative to minimize some of mainly relevant problems of world health, especially the public health network. This paper aimed to describe the socio-demographic and clinical population assisted by the Home Care Program HU em Casa, of the University Hospital Clemente de Faria, Universidade Estadual de Montes Claros. It is a descriptive and retrospective study analyzing
Kevin A Kwei
Full Text Available Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein levels, and strong immunostaining was observed in 25 of 54 (46% primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and identify GATA6 as a candidate lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies.
M A Wani
Full Text Available Background: An assessment of cancer incidence in population is required for prevention, early diagnosis, treatment and resource allocation. This will also guide in the formation of facilities for diagnosis, treatment, rehabilitation and follow-up for these patients. The demographic trend of cancer will help to identify common types and etiological factors. Efforts at clinical, research and administrative levels are needed to overcome this problem. Settings and Design: Present retro prospective study was conducted in regional cancer center of a tertiary care hospital. Materials and Methods: After permission from ethics committee, a retro prospective study of 1 year duration was undertaken to study the profile of cancer patients and to compare it with other cancer registries in India. Statistical Analysis: Pearson′s Chi-square test and simple linear regression were used. Statistical Package for the Social Sciences version-16 (University of Bristol information services (www.bristol.ac.uk/is/learning/resources was used. RESULTS: The overall incidence of cancer in Kashmir is on the increase and common sites of cancer are esophagus and gastroesophageal (GE junction, lung, stomach, colorectal, lymphomas, skin, laryngopharynx, acute leukemias, prostate and brain in males.In females common sites are breast, esophagus and GE junction, ovary, colorectal, stomach, lung, gallbladder, lymphomas, acute leukemias and brain. Conclusion: Cancers of esophagus, stomach and lungs have a high incidence both in men and women in Kashmir. Future studies on sources and types of environmental pollution and exposures in relation to these cancers may improve our understanding of risk factors held responsible for causation of these malignancies in this region. This will help in the allocation of available resources for prevention and treatment strategies.
Karemore, Gopal; Sujatha, .; Rai, Lavanya; Pai, Keerthilatha M.; Kartha, V. B.; Santhosh C., .
The serum protein profiles of normal subjects, patients diagnosed with cervical cancer, and oral cancer were recorded using High Performance Liquid Chromatography combined with Laser Induced Fluorescence detection (HPLC-LIF). Serum protein profiles of the above three classes were tested for establishing the ability of HPLC-LIF protein profiling technique for discrimination, using hard clustering and Fuzzy clustering methods. The clustering algorithms have quite successfully classified the profiles as belonging to normal, cancer of cervix, and oral cancer conditions.
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
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.
Full Text Available Fatima Zahra Laamiri,1 Azzedine Otmani,2 Samir Ahid,1,3 Amina Barkat11Faculty of Medicine and Pharmacy/Research Team in Maternal and Child Health and Nutrition, Mohammed V-Souissi University, Rabat, Morocco; 2National Institute of Oncology, Rabat, Morocco; 3Pharmacy Unit, National Institute of Oncology, Rabat, MoroccoBackground: Breast cancer has become the most common type of cancer in Morocco. In 2005, 127 new cases in women, representing 33.5% of female cancers, were added to the National Center of Oncology registry. The incidence of breast cancer is higher in Morocco than in the three other Maghreb countries, and it is significantly lower than in Western countries where it stands at over 80 cases per 100,000 people.Purpose: This 2-year long case-control study was conducted to assess the causal relationship between the lipid profile of overweight Moroccan women and breast cancer risk.Patients and methods: Overweight female patients with breast cancer (n = 400 were compared to 400 healthy controls at the National Institute of Oncology of Rabat. The epidemiological data on the disease and physical activity were gathered by interviewing the patients who had their lipid profile measured (total cholesterol, triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Body mass index was used to determine if patients were overweight.Results: Univariate analysis revealed a significant association between breast cancer and high body mass index (odds ratio [OR] = 1.31; 95% confidence interval [CI] = 1.25–1.37, menopause (OR = 2.68; 95% CI = 2–3.55, lack of physical activity (OR = 0.26; 95% CI = 0.21–0.31, and triglyceridemia (OR = 3.78; 95% CI = 2.73–5.23. Multivariate analysis revealed that the statistically significant increase in breast cancer risk was associated with a higher body mass index (OR = 1.11; 95% CI = 1.04–1.18, menopause (OR = 9.11; 95% CI = 4.76–17.47, and high triglyceride levels (OR = 4
Full Text Available Abstract 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 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 of patient at high risk for this disease; we provide pilot data for such a urinary bioassay. Furthermore, we demonstrate how the knowledge of networks, processes, and pathways altered in kidney cancer may be used to influence the choice of optimal therapy.
Hajiani Eskandar; Sarmast Shoshtari Mohammad Hossein; Masjedizadeh Rahim; Hashemi Jalal; Azmi Mehrdad; Tahereh Rajabi
AIM: To analyze the characteristics of epidemiological, clinical and survival patterns among patients with carcinoma of the stomach. METHODS: We retrospectively studied the characteristics of 186 gastric adenocarcinoma patients at Ahwaz Jundishapur University Hospitals (AJSUH) from September 1, 1996 to September 1, 2002. All the patients had histopathologicallyconfirmed malignancy. Demographic variables, family history of gastric cancer (GC), clinicopathologic characteristics and treatment-related variables were analyzed. Univariate analysis was performed with the log-rank test and multivariate analysis with Cox regression. P ＜ 0.05 was considered statistically significant. RESULTS: Male to female ratio was 2.6:1. The meanage was 60.6 years and 14% of the patients were younger than 40 years. Adenocarcinoma, gastric lymphoma, and gastric metastasis were found in 94.5%,2.3%, and 3% patients, respectively. There was an average of 6-mo delay between the initial symptoms and the diagnosis. Among adenocarcinoma groups, intestinal type was the commonest (55.9%) and the distal third was the most common localization (88.4%). One hundred and thirty-four patients (72.1%) were males. Thirty-one patients (17%) had a family history of GC. Surgery was performed in 90% of patients (non-curative).CONCLUSION: The epidemiological features of GC in south Iran mimic those in high-risk areas. There is a higher frequency of GC in young patients at our institution. Patients are detected and treated after a relatively long delay. Most patients present in advanced stages, which favors a poor overall survival. Family history of GC has a significant problem in our area. Studying the etiology of this cancer in south Iran and earlier diagnosis and subsequent better cares are recommended.
Jönsson, Jenny-Maria; Bartuma, Katarina; Dominguez-Valentin, Mev
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...... 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...
Kim, Minseok S; Kwon, Seyong; Kim, Taemin; Lee, Eun Sook; Park, Je-Kyun
This paper describes a multiplexed microfluidic immunohistochemistry (IHC)/immunocytochemistry (ICC) platform for quantitative proteomic profiling in breast cancer samples. Proteomic profiling via ICC was examined for four breast cancer cell lines (AU-565, HCC70, MCF-7, and SK-BR-3). The microfluidic device enabled 20 ICC assays on a biological specimen at the same time and a 16-fold decrease in time consumption, and could be used to quantitatively compare the expression level of each biomarker. The immunohistochemical staining from the microfluidic system showed an accurate localization of protein and comparable quality to that of the conventional IHC method. Although AU-565 and SK-BR-3 cell lines were classified by luminal subtype and adenocarcinomas and were derived from the same patient, weak p63 expression was seen only in SK-BR-3. The HCC70 cell line showed a triple-negative (estrogen receptor-negative/progesterone receptor-negative/human epidermal growth factor receptor 2-negative) phenotype and showed only cytokeratin 5 expression, a representative basal/myoepithelial cell marker. To demonstrate the applicability of the system to clinical samples for proteomic profiling, we were also able to apply this platform to human breast cancer tissue. This result indicates that the microfluidic IHC/ICC platform is useful for accurate histopathological diagnoses using numerous specific biomarkers simultaneously, facilitating the individualization of cancer therapy.
Gazzaniga, Paola; Naso, Giuseppe; Gradilone, Angela; Cortesi, Enrico; Gandini, Orietta; Gianni, Walter; Fabbri, Maria Agnese; Vincenzi, Bruno; di Silverio, Franco; Frati, Luigi; Aglianò, Anna Maria; Cristofanilli, Massimo
The prognostic value associated with the detection of circulating tumor cells (CTCs) in metastatic breast cancer by the CellSearch technology raise additional issues regarding the biological value of this information. We postulated that a drug-resistance profile of CTCs may predict response to chemotherapy in cancer patients and therefore could be used for patient selection. One hundred 5 patients with diagnosis of carcinoma were enrolled in a prospective trial. CTCs were isolated from peripheral blood, and positive samples were evaluated for the expression of a panel of genes involved in anticancer drugs resistance. The drug-resistance profile was correlated with disease-free survival (DFS; patients in adjuvant setting) and time to progression (TTP; metastatic patients) in a 24-months follow-up. Objective response correlation was a secondary end point. Fifty-one percent of patients were found positive for CTCs while all blood samples from healthy donors were negative. The drug-resistance profile correlates with DFS and TTP (p < 0.001 in both). Sensitivity of the test: able to predict treatment response in 98% of patients. Specificity of the test: 100%; no sample from healthy subject was positive for the presence of CTCs. Positive and negative predictive values were found to be 96.5 and 100%, respectively. We identified a drug-resistance profile of CTCs, which is predictive of response to chemotherapy, independent of tumor type and stage of disease. This approach may represent a first step toward the individualization of chemotherapy in cancer patients.
Jin-Shui Zhu; Hua Guo; Ming-Quan Song; Guo-Qiang Chen; Qun Sun; Qiang Zhang
AIM: To explore the expression of differential gene expression profiles of target cell between non-invasive submucosal and invasive advanced tumor in colon carcinoma using laser microdissection (LMD) in combination with polypeptide analysis.METHODS: Normal colon tissue samples from 20 healthy individuals and 30 cancer tissue samples from early non-invasive colon cancer cells were obtained. The cells from these samples were used LMD independently after P27-based amplification. aRNA from advanced colon cancer cells and metastatic cancer cells of 40 cases were applied to LMD and polypeptide analysis, semiquantitative reverse transcribed polymerase chain reaction (RT-PCR) and immunohistochemical assays were used to verify the results of microarray and further identify differentially expressed genes in non-invasive early stages of colon cancer.RESULTS: Five gene expressions were changed in colon carcinoma cells compared with that of controls. Of the five genes, three genes were downregulated and two were upregulated in invasive submucosal colon carcinoma compared with non-invasive cases. The results were confirmed at the level of aRNA and gene expression. Five genes were further identified as differentially expressed genes in the majority of cases (50%, 25/40) in progression of colon cancer, and their expression patterns of which were similar to tumor suppressor genes or oncogenes.CONCLUSION: This study suggested that combined use of polypeptide analysis might identify early expression profiles of five differential genes associated with the invasion of colon cancer. These results reveal that this gene may be a marker of submucosal invasion in early colon cancer.
Full Text Available Current clinical methods for cancer diagnosis and therapy have limitations, although survival periods are increasing as medical technologies develop. In most cancer cases, patient survival is closely related to cancer stage. Late-stage cancer after metastasis is very challenging to cure because current surgical removal of cancer is not precise enough and significantly affects bystander normal tissues. Moreover, the subsequent chemotherapy and radiation therapy affect not only malignant tumors, but also healthy tissues. Nanotechnologies for cancer treatment have the clear objective of solving these issues. Nanoparticles have been developed to more accurately differentiate early-stage malignant tumors and to treat only the tumors while dramatically minimizing side effects. In this review, we focus on recent chitosan-based nanoparticles developed with the goal of accurate cancer imaging and effective treatment. Regarding imaging applications, we review optical and magnetic resonance cancer imaging in particular. Regarding cancer treatments, we review various therapeutic methods that use chitosan-based nanoparticles, including chemo-, gene, photothermal, photodynamic and magnetic therapies.
Key, Jaehong; Park, Kyeongsoon
Current clinical methods for cancer diagnosis and therapy have limitations, although survival periods are increasing as medical technologies develop. In most cancer cases, patient survival is closely related to cancer stage. Late-stage cancer after metastasis is very challenging to cure because current surgical removal of cancer is not precise enough and significantly affects bystander normal tissues. Moreover, the subsequent chemotherapy and radiation therapy affect not only malignant tumors, but also healthy tissues. Nanotechnologies for cancer treatment have the clear objective of solving these issues. Nanoparticles have been developed to more accurately differentiate early-stage malignant tumors and to treat only the tumors while dramatically minimizing side effects. In this review, we focus on recent chitosan-based nanoparticles developed with the goal of accurate cancer imaging and effective treatment. Regarding imaging applications, we review optical and magnetic resonance cancer imaging in particular. Regarding cancer treatments, we review various therapeutic methods that use chitosan-based nanoparticles, including chemo-, gene, photothermal, photodynamic and magnetic therapies.
Biliary tract cancers (BTCs) are relatively uncommon orphan tumors that have an aggressive disease course and a poor clinical outcome. Surgery is the only curative treatment, but most patients present with advanced disease and therefore have a limited survival. Gemcitabine and cisplatin based chemotherapy has been the only widely accepted standard systemic therapy regimen in these patients but these tumors can be chemoresistant, further complicating their management. In recent times, there has been considerable research in the genetics of BTC and with the advent of new, advanced technologies like next-generation sequencing (NGS) we are achieving a greater understanding of its disease biology. With the help of NGS, we have now been able to identify actionable mutations such as in the isocitrate dehydrogenase 1 (IDH1), FGFR2, BRAF and HER2/neu genes for targeted therapeutics and correlate the genetic variations with distinct clinical prognoses. This recent genetic information has the potential to make precision medicine a part of routine clinical practice for the management of BTC patients. PMID:27747093
Full Text Available BACKGROUND : The changes in lipid profile have long been associated with cancer because lipids play a key role in maintenance of cell integrity. AIMS : The present study evaluated alterations in plasma lipid profile in untreated head and neck cancer patients as well as patients with oral precancerous conditions (OPC and its association with habit of tobacco consumption. MATERIAL AND METHODS : This hospital-based case control study included 184 head and neck cancer patients, 153 patients with OPC and 52 controls. Plasma lipids including: (i Total cholesterol, (ii LDL cholesterol (LDLC, (iii HDL cholesterol (HDLC (iv VLDL cholesterol (VLDLC and (v triglycerides were analysed by spectrophotometric kits. STATISTICAL ANALYSIS USED : Student′s t-test was performed to compare mean values of the parameters. RESULTS : A significant decrease in plasma total cholesterol and HDLC was observed in cancer patients (P=0.008 and P=0.000 respectively as well as in patients with OPC (P=0.014 and P=0.000, respectively as compared to the controls. The plasma VLDL and triglycerides levels were significantly lower in cancer patients as compared to the patients with OPC (P=0.04 and controls (P=0.059. The tobacco habituates showed lower plasma lipid levels than the non-habituates. Our data strengthen the evidence of an inverse relationship between plasma lipid levels and head and neck malignancies as well as OPC. CONCLUSION :The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization by neoplastic cells for new membrane biogenesis. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in head neck cancer patients.
Zhigang WANG; Weigang WANG; Wencai QIU; Youben FAN; Jun ZHAO; Yu WANG; Qi ZHENG
Ghrelin receptor has been shown to be expressed along the human gastrointestinal tract.Recent studies showed that ghrelin and a synthetic ghrelin receptor agonist improved weight gain and lean body mass retention in a rat model of cancer cachexia by acting on ghrelin receptor, that is, growth hormone secretagogue receptor (GHS-R). This study aims to explore the expression and the distribution of ghrelin receptor in human gastrointestinal tract cancers and to investigate the possible involvement of the ghrelin-GHS-R system in human digestive cancers. Surgical human digestive cancer specimens were obtained from various portions of the gastrointestinal tract from different patients. The expression of ghrelin receptor in these tissues was detected by tissue microarray technique. Our results showed that ghrelin receptor was expressed in cancers throughout the gastrointestinal tract, mainly in the cytoplasm of mucosal layer cells.Its expression level possibly correlated with organ type, histological grade, tumor-nodes-metastases stage,and nutrition status (weight loss) of the patients. For the first time, we identified the distribution of ghrelin receptor in digestive system cancers. Our results implied that the ghrelin-GHS-R system might be involved in the pathoclinical profiles of digestive cancers.
Full Text Available Introduction: Lung cancer is one of the leading causes of cancer related deaths in the world. The incidence of lung cancer is increasing in India and there is a need to understand the natural history of this disease. Aim of the study: To study the clinico- pathological- radiological profile of patients diagnosed with lung cancer from January 2013 to May 2015 at a tertiary care teaching hospital. Materials and Methods: Inpatient records of all patients admitted during the study period were examined and all patients with a histologically proven diagnosis of bronchogenic carcinoma were recruited. Demographic characteristics, clinical, radiological and pathological details of each patient were recorded. Results: Fifty four patients with lung cancer were identified. Forty three (79.6% were male and 11 (20.4% were female. Thirty two (59.7% were smokers and 22 (40.7% were non smokers. Cough and expectoration (61.1% was the most common presenting symptom followed by breathlessness (59.3%. Mass lesion (81.5% was the most common radiological presentation and adenocarcinoma (42.6% was the most common histological subtype. When compared to fiber optic bronchoscopy, image guided percutaneous biopsy had a better yield for diagnosing lung cancer (51.9% vs 48.1%. But this difference was not statistically significant (p=0.892 Conclusion: Adenocarcinoma is replacing squamous cell carcinoma as the most common type of lung cancer in India.
Martin, Cara M
Cervical cancer, a potentially preventable disease, remains the second most common malignancy in women worldwide. Human papillomavirus is the single most important etiological agent in cervical cancer. HPV contributes to neoplastic progression through the action of two viral oncoproteins E6 and E7, which interfere with critical cell cycle pathways, p53, and retinoblastoma. However, evidence suggests that HPV infection alone is insufficient to induce malignant changes and other host genetic variations are important in the development of cervical cancer. Advances in molecular biology and high throughput gene expression profiling technologies have heralded a new era in biomarker discovery and identification of molecular targets related to carcinogenesis. These advancements have improved our understanding of carcinogenesis and will facilitate screening, early detection, management, and personalised targeted therapy. In this chapter, we have described the use of high density microarrays to assess gene expression profiles in cervical cancer. Using this approach we have identified a number of novel genes which are differentially expressed in cervical cancer, including several genes involved in cell cycle regulation. These include p16ink4a, MCM 3 and 5, CDC6, Geminin, Cyclins A-D, TOPO2A, CDCA1, and BIRC5. We have validated expression of mRNA using real-time PCR and protein by immunohistochemistry.
Kim, Sang Woo; Fishilevich, Elane; Arango-Argoty, Gustavo; Lin, Yuefeng; Liu, Guodong; Li, Zhihua; Monaghan, A Paula; Nichols, Mark; John, Bino
Non-coding RNAs (ncRNAs) play major roles in development and cancer progression. To identify novel ncRNAs that may identify key pathways in breast cancer development, we performed high-throughput transcript profiling of tumor and normal matched-pair tissue samples. Initial transcriptome profiling using high-density genome-wide tiling arrays revealed changes in over 200 novel candidate genomic regions that map to intronic regions. Sixteen genomic loci were identified that map to the long introns of five key protein-coding genes, CRIM1, EPAS1, ZEB2, RBMS1, and RFX2. Consistent with the known role of the tumor suppressor ZEB2 in the cancer-associated epithelial to mesenchymal transition (EMT), in situ hybridization reveals that the intronic regions deriving from ZEB2 as well as those from RFX2 and EPAS1 are down-regulated in cells of epithelial morphology, suggesting that these regions may be important for maintaining normal epithelial cell morphology. Paired-end deep sequencing analysis reveals a large number of distinct genomic clusters with no coding potential within the introns of these genes. These novel transcripts are only transcribed from the coding strand. A comprehensive search for breast cancer associated genes reveals enrichment for transcribed intronic regions from these loci, pointing to an underappreciated role of introns or mechanisms relating to their biology in EMT and breast cancer.
Sang Woo Kim
Full Text Available Non-coding RNAs (ncRNAs play major roles in development and cancer progression. To identify novel ncRNAs that may identify key pathways in breast cancer development, we performed high-throughput transcript profiling of tumor and normal matched-pair tissue samples. Initial transcriptome profiling using high-density genome-wide tiling arrays revealed changes in over 200 novel candidate genomic regions that map to intronic regions. Sixteen genomic loci were identified that map to the long introns of five key protein-coding genes, CRIM1, EPAS1, ZEB2, RBMS1, and RFX2. Consistent with the known role of the tumor suppressor ZEB2 in the cancer-associated epithelial to mesenchymal transition (EMT, in situ hybridization reveals that the intronic regions deriving from ZEB2 as well as those from RFX2 and EPAS1 are down-regulated in cells of epithelial morphology, suggesting that these regions may be important for maintaining normal epithelial cell morphology. Paired-end deep sequencing analysis reveals a large number of distinct genomic clusters with no coding potential within the introns of these genes. These novel transcripts are only transcribed from the coding strand. A comprehensive search for breast cancer associated genes reveals enrichment for transcribed intronic regions from these loci, pointing to an underappreciated role of introns or mechanisms relating to their biology in EMT and breast cancer.
Full Text Available 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
Queiroz, Ana Carolina de Castro Mendonça; Mota, Dálete Delalibera Corrêa de Faria; Bachion, Maria Marcia; Ferreira, Ana Cássia Mendes
Persons in palliative care develop pressure ulcers (PU) as death approaches, but the extent of the problem is still unknown. The objectives were to identify the prevalence of pressure ulcers in people with cancer in palliative home care, compare the socio-demographic and clinical profile of patients with and without pressure ulcers, and analyze the characteristics of the ulcers. This descriptive, cross-sectional study included 64 people with advanced cancer in palliative home care. Twelve of them (18.8%) had PU, of whom 75.0% were men. The participants had one to three PU, amounting to 19 lesions, 89.4% of those developed at home and 47.4% at stage 3. The presence of PU was higher among those who had a history of previous wound. PU consisted of a significant event occurring in the studied population, indicating that preventive measures should be included in the home palliative care health team.
Ming-Shiang Wu; Yi-Shing Lin; Yu-Ting Chang; Chia-Tung Shun; Ming-Tsan Lin; Jaw-Town Lin
AIM: To examine the gene expression profile of gastric cancer (GC) by combination of laser capture microdissection (LCM) and microarray and to correlate the profiling with histological subtypes. METHODS: Using LCM, pure cancer cells were procured from 45 cancerous tissues. After procurement of about 5 000 cells, total RNA was extracted and the quality of RNA was determined before further amplification and hybridization. One microgram of amplified RNA was converted to cDNA and hybridized to cDNA microarray. RESULTS: Among 45 cases, only 21 were qualified for their RNAs. A total of 62 arrays were performed. These included 42 arrays for cancer (21 cases with dyeswab duplication) and 20 arrays for non-tumorous cells (10 cases with dye-swab duplication) with universal reference. Analyzed data showed 504 genes were differentially expressed and could distinguish cancerous and non-cancerous groups with more than 99% accuracy. Of the 504 genes, trefoil factors 1, 2, and 3 were in the list and their expression patterns were consistent with previous reports. Immunohistochemical staining of trefoil factor 1 was also consistent with the array data. Analyses of the tumor group with these 504 genes showed that there were 3 subgroups of GC that did not correspond to any current classification system, including Lauren's classification. CONCLUSION: By using LCM, linear amplification of RNA, and cDNA microarray, we have identified a panel of genes that have the power to discriminate between GC and non-cancer groups. The new molecular classification and the identified novel genes in gastric carcinogenesis deserve further investigations to elucidate their dinicopathological significance.
Kapil H Agrawal
Full Text Available Background: India is heading towards various types of non-communicable diseases, which are also known as modern epidemics. Among these modern epidemics cancer is among the ten commonest cause of mortality in developing countries including India. Oral cancer is a major problem in India and accounts for 50-70% of all the cancers diagnosed. Ninety percent (90% of oral cancers in South East Asia including India are linked to tobacco chewing and tobacco smoking. Research question: What is the profile of Oral cancer (Oral cavity cases reported in the hospital? Objective: To study the clinico-epidemiological profile associated with Oral cancer cases. Methods: Study Design: Hospital based, Cross -sectional study. Settings: Shri Siddhivinayak Ganapati Cancer Hospital, Miraj, Maharashtra. Participants and Sample size: As it is a time bound study sample size comprised of all the confirmed cases of oral cancer reported in the hospital during the study period. The study was carried out from 1st March 2005 to 28th February 2006. Study variables included demographic factors, socioeconomic factors, enquiries regarding modifiable risk factors such as tobacco usage, alcohol consumption, site involved (within oral cavity, staging, histopathological examination, treatment modality used. Data entry and statistical analysis was done using Microsoft excel. Data presented in form of percentages and proportions. Results: Out of the total 160 cases, majority of the subjects were above 40 years age. 36 (22% of subjects were young adults (below 40 years age. 125 (78% subjects were male. Most of the subjects belonged to upper lower and lower middle socio-economic scale according to modified Kuppuswamy classification. It was observed that 139 (87% cases consumed tobacco in all forms. Out of these, ninety cases consumed tobacco in chewable form. Tobacco was chewed mainly in the form of gutka. Only ten (10 female subjects chewed tobacco. No female subjects smoked. The most
Full Text Available Identification of gene expression profiles of cancer stem cells may have significant implications in the understanding of tumor biology and for the design of novel treatments targeted toward these cells. Here we report a potential ovarian cancer stem cell gene expression profile from isolated side population of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma. Affymetrix U133 Plus 2.0 microarrays were used to interrogate the differentially expressed genes between side population (SP and main population (MP, and the results were analyzed by paired T-test using BRB-ArrayTools. We identified 138 up-regulated and 302 down-regulated genes that were differentially expressed between all 10 SP/MP pairs. Microarray data was validated using qRT-PCR and17/19 (89.5% genes showed robust correlations between microarray and qRT-PCR expression data. The Pathway Studio analysis identified several genes involved in cell survival, differentiation, proliferation, and apoptosis which are unique to SP cells and a mechanism for the activation of Notch signaling is identified. To validate these findings, we have identified and isolated SP cells enriched for cancer stem cells from human ovarian cancer cell lines. The SP populations were having a higher colony forming efficiency in comparison to its MP counterpart and also capable of sustained expansion and differentiation in to SP and MP phenotypes. 50,000 SP cells produced tumor in nude mice whereas the same number of MP cells failed to give any tumor at 8 weeks after injection. The SP cells demonstrated a dose dependent sensitivity to specific γ-secretase inhibitors implicating the role of Notch signaling pathway in SP cell survival. Further the generated SP gene list was found to be enriched in recurrent ovarian cancer tumors.
Liang, Yuh-Jin; Ding, Yao; Levery, Steven B; Lobaton, Marlin; Handa, Kazuko; Hakomori, Sen-itiroh
Previous studies demonstrated that certain glycosphingolipids (GSLs) are involved in various cell functions, such as cell growth and motility. Recent studies showed changes in GSL expression during differentiation of human embryonic stem cells; however, little is known about expression profiles of GSLs in cancer stem cells (CSCs). CSCs are a small subpopulation in cancer and are proposed as cancer-initiating cells, have been shown to be resistant to numerous chemotherapies, and may cause cancer recurrence. Here, we analyzed GSLs expressed in human breast CSCs by applying a CSC model induced through epithelial-mesenchymal transition, using mass spectrometry, TLC immunostaining, and cell staining. We found that (i) Fuc-(n)Lc4Cer and Gb3Cer were drastically reduced in CSCs, whereas GD2, GD3, GM2, and GD1a were greatly increased in CSCs; (ii) among various glycosyltransferases tested, mRNA levels for ST3GAL5, B4GALNT1, ST8SIA1, and ST3GAL2 were increased in CSCs, which could explain the increased expression of GD3, GD2, GM2, and GD1a in CSCs; (iii) the majority of GD2+ cells and GD3+ cells were detected in the CD44(hi)/CD24(lo) cell population; and (iv) knockdown of ST8SIA1 and B4GALNT1 significantly reduced the expression of GD2 and GD3 and caused a phenotype change from CSC to a non-CSC, which was detected by reduced mammosphere formation and cell motility. Our results provide insight into GSL profiles in human breast CSCs, indicate a functional role of GD2 and GD3 in CSCs, and suggest a possible novel approach in targeting human breast CSCs to interfere with cancer recurrence.
Full Text Available BACKGROUND: Recently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection. METHODS AND FINDINGS: Plasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC-electrospray ionization (ESI-mass spectrometry (MS. Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer, regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling. CONCLUSIONS: These findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a
Markiewicz, Aleksandra [Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk 80-211 (Poland); Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw 02-091 (Poland); Książkiewicz, Magdalena [Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk 80-211 (Poland); Seroczyńska, Barbara [Bank of Frozen Tissues and Genetic Specimens, Department of Medical Laboratory Diagnostics, Medical University of Gdańsk, Gdańsk 80-211 (Poland); Skokowski, Jarosław [Bank of Frozen Tissues and Genetic Specimens, Department of Medical Laboratory Diagnostics, Medical University of Gdańsk, Gdańsk 80-211 (Poland); Department of Surgical Oncology, Medical University of Gdańsk, Gdańsk 80-214 (Poland); Szade, Jolanta [Department of Pathomorphology, Medical University of Gdańsk, Gdańsk 80-214 (Poland); Wełnicka-Jaśkiewicz, Marzena [Department of Oncology and Radiotherapy, Medical University of Gdańsk, Gdańsk 80-211 (Poland); Zaczek, Anna J., E-mail: email@example.com [Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Gdańsk 80-211 (Poland)
Breast cancers can metastasize via hematogenous and lymphatic routes, however in some patients only one type of metastases are detected, suggesting a certain proclivity in metastatic patterns. Since epithelial-mesenchymal transition (EMT) plays an important role in cancer dissemination it would be worthwhile to find if a specific profile of EMT gene expression exists that is related to either lymphatic or hematogenous dissemination. Our study aimed at evaluating gene expression profile of EMT-related markers in primary tumors (PT) and correlated them with the pattern of metastatic spread. From 99 early breast cancer patients peripheral blood samples (N = 99), matched PT (N = 47) and lymph node metastases (LNM; N = 22) were collected. Expression of TWIST1, SNAI1, SNAI2 and VIM was analyzed in those samples. Additionally expression of CK19, MGB1 and HER2 was measured in CTCs-enriched blood fractions (CTCs-EBF). Results were correlated with each other and with clinico-pathological data of the patients. Results show that the mesenchymal phenotype of CTCs-EBF correlated with poor clinico-pathological characteristics of the patients. Additionally, PT shared more similarities with LNM than with CTCs-EBF. Nevertheless, LNM showed increased expression of EMT-related markers than PT; and EMT itself in PT did not seem to be necessary for lymphatic dissemination.
Ali Hassan, Nur Zarina; Mokhtar, Norfilza Mohd; Kok Sin, Teow; Mohamed Rose, Isa; Sagap, Ismail; Harun, Roslan; Jamal, Rahman
Integrative analyses of multiple genomic datasets for selected samples can provide better insight into the overall data and can enhance our knowledge of cancer. The objective of this study was to elucidate the association between copy number variation (CNV) and gene expression in colorectal cancer (CRC) samples and their corresponding non-cancerous tissues. Sixty-four paired CRC samples from the same patients were subjected to CNV profiling using the Illumina HumanOmni1-Quad assay, and validation was performed using multiplex ligation probe amplification method. Genome-wide expression profiling was performed on 15 paired samples from the same group of patients using the Affymetrix Human Gene 1.0 ST array. Significant genes obtained from both array results were then overlapped. To identify molecular pathways, the data were mapped to the KEGG database. Whole genome CNV analysis that compared primary tumor and non-cancerous epithelium revealed gains in 1638 genes and losses in 36 genes. Significant gains were mostly found in chromosome 20 at position 20q12 with a frequency of 45.31% in tumor samples. Examples of genes that were associated at this cytoband were PTPRT, EMILIN3 and CHD6. The highest number of losses was detected at chromosome 8, position 8p23.2 with 17.19% occurrence in all tumor samples. Among the genes found at this cytoband were CSMD1 and DLC1. Genome-wide expression profiling showed 709 genes to be up-regulated and 699 genes to be down-regulated in CRC compared to non-cancerous samples. Integration of these two datasets identified 56 overlapping genes, which were located in chromosomes 8, 20 and 22. MLPA confirmed that the CRC samples had the highest gains in chromosome 20 compared to the reference samples. Interpretation of the CNV data in the context of the transcriptome via integrative analyses may provide more in-depth knowledge of the genomic landscape of CRC.
Nur Zarina Ali Hassan
Full Text Available Integrative analyses of multiple genomic datasets for selected samples can provide better insight into the overall data and can enhance our knowledge of cancer. The objective of this study was to elucidate the association between copy number variation (CNV and gene expression in colorectal cancer (CRC samples and their corresponding non-cancerous tissues. Sixty-four paired CRC samples from the same patients were subjected to CNV profiling using the Illumina HumanOmni1-Quad assay, and validation was performed using multiplex ligation probe amplification method. Genome-wide expression profiling was performed on 15 paired samples from the same group of patients using the Affymetrix Human Gene 1.0 ST array. Significant genes obtained from both array results were then overlapped. To identify molecular pathways, the data were mapped to the KEGG database. Whole genome CNV analysis that compared primary tumor and non-cancerous epithelium revealed gains in 1638 genes and losses in 36 genes. Significant gains were mostly found in chromosome 20 at position 20q12 with a frequency of 45.31% in tumor samples. Examples of genes that were associated at this cytoband were PTPRT, EMILIN3 and CHD6. The highest number of losses was detected at chromosome 8, position 8p23.2 with 17.19% occurrence in all tumor samples. Among the genes found at this cytoband were CSMD1 and DLC1. Genome-wide expression profiling showed 709 genes to be up-regulated and 699 genes to be down-regulated in CRC compared to non-cancerous samples. Integration of these two datasets identified 56 overlapping genes, which were located in chromosomes 8, 20 and 22. MLPA confirmed that the CRC samples had the highest gains in chromosome 20 compared to the reference samples. Interpretation of the CNV data in the context of the transcriptome via integrative analyses may provide more in-depth knowledge of the genomic landscape of CRC.
Wang, Ning; Docherty, Freyja E; Brown, Hannah K; Reeves, Kimberley J; Fowles, Anne C M; Ottewell, Penelope D; Dear, T Neil; Holen, Ingunn; Croucher, Peter I; Eaton, Colby L
It has been suggested that metastasis-initiating cells gain a foothold in bone by homing to a metastastatic microenvironment (or "niche"). Whereas the precise nature of this niche remains to be established, it is likely to contain bone cell populations including osteoblasts and osteoclasts. In the mouse tibia, the distribution of osteoblasts on endocortical bone surfaces is non-uniform, and we hypothesize that studying co-localization of individual tumor cells with resident cell populations will reveal the identity of critical cellular components of the niche. In this study, we have mapped the distribution of three human prostate cancer cell lines (PC3-NW1, LN-CaP, and C4 2B4) colonizing the tibiae of athymic mice following intracardiac injection and evaluated their interaction with potential metastatic niches. Prostate cancer cells labeled with the fluorescent cell membrane dye (Vybrant DiD) were found by two-photon microscopy to be engrafted in the tibiae in close proximity (∼40 µm) to bone surfaces and 70% more cancer cells were detected in the lateral compared to the medial endocortical bone regions. This was associated with a 5-fold higher number of osteoblasts and 7-fold higher bone formation rate on the lateral endocortical bone surface compared to the medial side. By disrupting cellular interactions mediated by the chemokine (C-X-C motif) receptor 4 (CXCR4)/chemokine ligand 12 (CXCL12) axis with the CXCR4 inhibitor AMD3100, the preferential homing pattern of prostate cancer cells to osteoblast-rich bone surfaces was disrupted. In this study, we map the location of prostate cancer cells that home to endocortical regions in bone and our data demonstrate that homing of prostate cancer cells is associated with the presence and activity of osteoblast lineage cells, and suggest that therapies targeting osteoblast niches should be considered to prevent development of incurable prostate cancer bone metastases.
Christina Marie Gutierrez
Full Text Available Background/Aims: Early parity reduces breast cancer risk, whereas, late parity and nulliparity increase breast cancer risk. Despite substantial efforts to understand the protective effects of early parity, the precise molecular circuitry responsible for these changes is not yet fully defined. Methods: Here, we have conducted the first study assessing protein expression profiles in normal breast tissue of healthy early parous, late parous, and nulliparous women. Breast tissue biopsies were obtained from 132 healthy parous and nulliparous volunteers. These samples were subjected to global protein expression profiling and immunohistochemistry. GeneSpring and MetaCore bioinformatics analysis software were used to identify protein expression profiles associated with early parity (low risk versus late/nulliparity (high risk. Results: Early parity reduces expression of key proteins involved in mitogenic signaling pathways in breast tissue through down regulation of EGFR1/3, ESR1, AKT1, ATF, Fos, and SRC. Early parity is also characterized by greater genomic stability and reduced tissue inflammation based on differential expression of aurora kinases, p53, RAD52, BRCA1, MAPKAPK-2, ATF-1, ICAM1, and NF-kappaB compared to late and nulli parity. Conclusions: Early parity reduces basal cell proliferation in breast tissue, which translates to enhanced genomic stability, reduced cellular stress/inflammation, and thus reduced breast cancer risk.
Couraud, Sébastien; Debieuvre, Didier; Moreau, Lionel; Dumont, Patrick; Margery, Jacques; Quoix, Elisabeth; Duvert, Bernard; Cellerin, Laurent; Baize, Nathalie; Taviot, Bruno; Coudurier, Marie; Cadranel, Jacques; Missy, Pascale; Morin, Franck; Mornex, Jean-François; Zalcman, Gérard; Souquet, Pierre-Jean
EGFR and HER2 mutations and ALK rearrangement are known to be related to lung cancer in never-smokers, while KRAS, BRAF and PIK3CA mutations are typically observed among smokers. There is still debate surrounding whether never-smokers exposed to passive smoke exhibit a "smoker-like" somatic profile compared with unexposed never-smokers. Passive smoke exposure was assessed in the French BioCAST/IFCT-1002 never-smoker lung cancer cohort and routine molecular profiles analyses were compiled. Of the 384 patients recruited into BioCAST, 319 were tested for at least one biomarker and provided data relating to passive smoking. Overall, 219 (66%) reported having been exposed to passive smoking. No significant difference was observed between mutation frequency and passive smoke exposure (EGFR mutation: 46% in never exposed versus 41% in ever exposed; KRAS: 7% versus 7%; ALK: 13% versus 11%; HER2: 4% versus 5%; BRAF: 6% versus 5%; PIK3CA: 4% versus 2%). We observed a nonsignificant trend for a negative association between EGFR mutation and cumulative duration of passive smoke exposure. No association was found for other biomarkers. There is no clear association between passive smoke exposure and somatic profile in lifelong, never-smoker lung cancer.
Full Text Available 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
A family-run nursing home that gives elderly people the feel of a real of a real home Jiang Shaoju’s three-year-old family-run nursing home for the elderly in Dalian breaks all stereotypes people might attach to traditional homes for the aged.There are no nurses in uniforms,no numbered bedding and there is a lot of laughter. Jiang,56,has given almost every one of the 12 elderly women in her nursing home a nickname.She calls 92-year-old Xuan Shoulan"vice principal"because Xuan likes giving orders to others in the house and
Full Text Available Abstract 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.
Friedrichsen, Maria; Lindholm, Ann; Milberg, Anna
Objective: The aim of this study was to explore the experiences and preferences of terminally ill cancer patients regarding truth telling in the communication of poor prognoses. Method: We recorded and transcribed interviews with 45 patients who knew their cancer was terminal, and analyzed their responses hermeneutically. Results: Patients identified three different modes of truth: (1) the absolute objective truth that they are dying; (2) the partial truth about their condition including some...
Heegaard, Niels H H; Schetter, Aaron J; Welsh, Judith A; Yoneda, Mitsuhiro; Bowman, Elise D; Harris, Curtis C
Circulating micro-RNA (miR) profiles have been proposed as promising diagnostic and prognostic biomarkers for cancer, including lung cancer. We have developed methods to accurately and reproducibly measure micro-RNA levels in serum and plasma. Here, we study paired serum and plasma samples from 220 patients with early stage nonsmall cell lung cancer (NSCLC) and 220 matched controls. We use qRT-PCR to measure the circulating levels of 30 different miRs that have previously been reported to be differently expressed in lung cancer tissue. Duplicate RNA extractions were performed for 10% of all samples, and micro-RNA measurements were highly correlated among those duplicates. This demonstrates high reproducibility of our assay. The expressions of miR-146b, miR-221, let-7a, miR-155, miR-17-5p, miR-27a and miR-106a were significantly reduced in the serum of NSCLC cases, while miR-29c was significantly increased. No significant differences were observed in plasma of patients compared with controls. Overall, expression levels in serum did not correlate well with levels in plasma. In secondary analyses, reduced plasma expression of let-7b was modestly associated with worse cancer-specific mortality in all patients, and reduced serum expression of miR-223 was modestly associated with cancer-specific mortality in stage IA/B patients. MiR profiles also showed considerable differences comparing African American and European Americans. In summary, we found significant differences in miR expression when comparing cases and controls and find evidence that expression of let-7b is associated with prognosis in NSCLC.
Sørensen, Brita Singers; Knudsen, Anders Bisgård; Wittrup, Catja Foged
genes, with BNIP3 not being upregulated at hypoxic conditions in 3 out of 6 colon cancer cell lines, and ALDOA in OE21 and FAM162A and SLC2A1 in SW116 only showing limited hypoxia induction. Furthermore, in the esophagus cell lines, the normoxic and hypoxic expression levels of LOX and BNIP3 were below......BACKGROUND AND PURPOSE: A 15-gene hypoxia profile has previously demonstrated to have both prognostic and predictive impact for hypoxic modification in squamous cell carcinoma of the head and neck. This gene expression profile may also have a prognostic value in other histological cancer types...... the tissue type dependency of hypoxia induced genes included in a 15-gene hypoxic profile in carcinoma cell lines from prostate, colon, and esophagus cancer, and demonstrated that in vitro, with minor fluctuations, the genes in the hypoxic profile are hypoxia inducible, and the hypoxia profile may...
Cancer-associated fibroblasts (CAF) influence tumor development at primary as well as in metastatic sites, but there have been no direct comparisons of the transcriptional profiles of stromal cells from different tumor sites. In this study, we used customized cDNA microarrays to compare the gene expression profile of stromal cells from primary tumor (CAF, n = 4), lymph node metastasis (N+, n = 3) and bone marrow (BM, n = 4) obtained from breast cancer patients. Biological validation was done ...
Chuan-Ding Yu; Shen-Hua Xu; Hang-Zhou Mou; Zhi-Ming Jiang; Chi-Hong Zhu; Xiang-Lin Liu
AIM: To study the difference of gene expression in gastric cancer (T), pericancerous epithelium (P) and normal tissue of gastric mucosa (C), and to screen an associated novel gene in early gastric carcinogenesis by oligonudeotide microarray.METHODS: U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T, P and C, respectively. Bioinformatics was used to analyze the detected results.RESULTS: When gastric cancer was compared with normal gastric mucosa, 766 genes were found, with a difference of more than four times in expression levels. Of the 766 genes,530 were up-regulated (Signal Log Ratio [SLR]＞2), and 236 were down-regulated (SLR＜-2). When pericancerous epithelium was compared with normal gastric mucosa, 64genes were found, with a difference of more than four times in expression levels. Of the 64 genes, 50 were up-regulated (SLR＞2), and 14 were down-regulated (SLR＜-2). Compared with normal gastric mucosa, a total of 143 genes with a difference in expression levels (more than four times, either in cancer or in pericancerous epithelium) were found in gastric cancer (T) and pericancerous epithelium (P). Of the 143 genes, 108 were up-regulated (SLR＞2), and 35were down-regulated (SLR＜-2).CONCLUSION: To apply a gene chip could find 143 genes associated with the genes of gastric cancer in pericancerous epithelium, although there were no pathological changes in the tissue slices. More interesting, six genes of pericancerous epithelium were up-regulated in comparison with genes of gastric cancer and three genes were down-regulated in comparison with genes of gastric cancer. It is suggested that these genes may be related to the carcinogenesis and development of early gastric cancer.
Lizotte, Patrick H.; Ivanova, Elena V.; Awad, Mark M.; Jones, Robert E.; Keogh, Lauren; Liu, Hongye; Dries, Ruben; Herter-Sprie, Grit S.; Santos, Abigail; Feeney, Nora B.; Paweletz, Cloud P.; Kulkarni, Meghana M.; Bass, Adam J.; Rustgi, Anil K.; Yuan, Guo-Cheng; Kufe, Donald W.; Jänne, Pasi A.; Hammerman, Peter S.; Sholl, Lynette M.; Hodi, F. Stephen; Richards, William G.; Bueno, Raphael; English, Jessie M.; Bittinger, Mark A.
BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non–small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC). RESULTS. Cytometric profiling identified an immunologically “hot” cluster with abundant CD8+ T cells expressing high levels of PD-1 and TIM-3 and an immunologically “cold” cluster with lower relative abundance of CD8+ T cells and expression of inhibitory markers. The “hot” cluster was highly enriched for expression of genes associated with T cell trafficking and cytotoxic function and high PD-L1 expression by IHC. There was no correlation between immunophenotype and KRAS or EGFR mutation, or patient smoking history, but we did observe an enrichment of squamous subtype and tumors with higher mutation burden in the “hot” cluster. Additionally, approximately 20% of cases had high B cell infiltrates with a subset producing IL-10. CONCLUSIONS. Our results support the use of immune-based metrics to study response and resistance to immunotherapy in lung cancer. FUNDING. The Robert A. and Renée E. Belfer Family Foundation, Expect Miracles Foundation, Starr Cancer Consortium, Stand Up to Cancer Foundation, Conquer Cancer Foundation, International Association for the Study of Lung Cancer, National Cancer Institute (R01 CA205150), and the Damon Runyon Cancer Research Foundation. PMID:27699239
Villumsen, Brigitta R.; Grønbech Jørgensen, Martin; Frystyk, Jan
will explore the satisfaction and experience with the health game programme. To the best of our knowledge this is the first RCT study to investigate the effect of a home based health game programme on PC patients. No statistical analysis have been made thus far because inclusion is ongoing, however baseline...... observations show that most of the participants fulfil the criteria for being diagnosed with metabolic syndrome. Finally this study will assess the safety and efficacy of a novel exergaming modality for PC patients and the results are expected to influence recommendations on exercise given to this patient...
Kim, Young Ok; Suarez, Marie L.; Dauw, Colleen M.; Stapleton, Stephen J.; Gorman, Geraldine; Storfjell, Judith; Zhao, Zhongsheng
Abstract We aimed to determine the acceptability and feasibility of a pentablet-based software program, PAINReportIt®-Plus, as a means for patients with cancer in home hospice to report their symptoms and differences in acceptability by demographic variables. Of the 131 participants (mean age = 59 ± 13, 58% women, 48.1% African American), 44% had never used a computer, but all participants easily used the computerized tool and reported an average computer acceptability score of 10.3 ± 1.8, indicating high acceptability. Participants required an average of 19.1 ± 9.5 minutes to complete the pain section, 9.8 ± 6.5 minutes for the medication section, and 4.8 ± 2.3 minutes for the symptom section. The acceptability scores were not statistically different by demographic variables but time to complete the tool differed by racial/ethnic groups. Our findings demonstrate that terminally ill patients with cancer are willing and able to utilize computer pentablet technology to record and describe their pain and other symptoms. Visibility of pain and distress is the first step necessary for the hospice team to develop a care plan for improving control of noxious symptoms. PMID:19594343
Ducancelle, Alexandra; Reiser, Justine; Pivert, Adeline; Le Guillou-Guillemette, Hélène; Le Duc-Banaszuk, Anne Sophie; Lunel-Fabiani, Françoise
In France, cervical cancer screening is currently based on cytological examination of a Pap smear for women aged 25 to 65, but screening coverage is unsatisfactory. Previous studies have shown that self-sampling for human papillomavirus (HPV) testing increases rates of compliance. With this purpose in mind, we performed the CapU study to evaluate the acceptance of a urinary HPV test. Letters proposing a new cervical cancer screening method using at-home urine self-sampling were sent to 5000 women aged 40-65 years who had not had a Pap smear over the past three years. The participating patients had to send their urine samples to the Angers Hospital Virology Laboratory for analysis using real-time PCR. Of the 771 samples received, 687 were analyzed. High-risk HPV were detected in 29 women. In follow-up, 28 women with positive urinary HPV results had a Pap smear or colposcopy done. The cytological results showed nine abnormal Pap smears, among which histology studies confirmed three cases of cervical intraepithelial neoplasia grade III lesions. Our study shows that urinary HPV testing may be pertinent to women who do not have cervical Pap smears done and lead to the diagnosis of high-grade cervical lesions.
In this article, we introduce a robust and efficient strategy for deriving global and allele-specific copy number alternations (CNA) from cancer whole exome sequencing data based on Log R ratios and B-allele frequencies. Applying the approach to the analysis of over 200 skin cancer samples, we demonstrate its utility for discovering distinct CNA events and for deriving ancillary information such as tumor purity. Availability and implementation: https://github.com/xfwang/CLOSE CONTACT: firstname.lastname@example.org or email@example.com. (Publication Abstract)
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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…
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Full Text Available Background: The present study was undertaken to estimate and compare the levels of plasma total cholesterol (TC, low density lipoprotein (LDL, high density lipoprotein (HDL, very low density lipoprotein (VLDL and triglycerides in patients with oral precancerous lesions/conditions, oral cancer and normal subjects. Materials and Methods: The study comprised of 60 patients with oral precancerous lesions/conditions, 60 patients with oral cancer and a control group of 60 healthy individuals. The diagnosis of oral precancerous lesions/conditions and oral cancer was confirmed histopathologically. Under aseptic condition 5 ml venous blood of overnight fasting patient was withdrawn from each individual. Serum was separated by centrifugation and plasma levels of TC, LDL, HDL, VLDL and triglycerides were estimated. Descriptive statistical analysis has been carried out in the present study. Analysis of variance has been used to find the significance of study parameters between three or more groups of patients, Post-hoc test as Tukey has been used to find the pair wise significance. Significance is assessed at 5% level of significance. Results: Statistically significant decrease in levels of plasma TC, LDL, HDL, VLDL and triglycerides was observed in the precancerous and cancerous groups as compared to the control group. On comparison between precancerous and cancerous groups, significant decrease was observed in cancerous group. Conclusion: The change in lipid levels may have an early diagnostic or prognostic role in the oral premalignant lesions/conditions and oral cancer. The presence of decreased plasma lipid profile should increase the suspicion of these lesions to be investigated further.
Full Text Available Heritable factors are evidently involved in prostate cancer (PrCa carcinogenesis, but currently, genetic markers are not routinely used in screening or diagnostics of the disease. More precise information is needed for making treatment decisions to distinguish aggressive cases from indolent disease, for which heritable factors could be a useful tool. The genetic makeup of PrCa has only recently begun to be unravelled through large-scale genome-wide association studies (GWAS. The thus far identified Single Nucleotide Polymorphisms (SNPs explain, however, only a fraction of familial clustering. Moreover, the known risk SNPs are not associated with the clinical outcome of the disease, such as aggressive or metastasised disease, and therefore cannot be used to predict the prognosis. Annotating the SNPs with deep clinical data together with miRNA expression profiles can improve the understanding of the underlying mechanisms of different phenotypes of prostate cancer.In this study microRNA (miRNA profiles were studied as potential biomarkers to predict the disease outcome. The study subjects were from Finnish high risk prostate cancer families. To identify potential biomarkers we combined a novel non-parametrical test with an importance measure provided from a Random Forest classifier. This combination delivered a set of nine miRNAs that was able to separate cases from controls. The detected miRNA expression profiles could predict the development of the disease years before the actual PrCa diagnosis or detect the existence of other cancers in the studied individuals. Furthermore, using an expression Quantitative Trait Loci (eQTL analysis, regulatory SNPs for miRNA miR-483-3p that were also directly associated with PrCa were found.Based on our findings, we suggest that blood-based miRNA expression profiling can be used in the diagnosis and maybe even prognosis of the disease. In the future, miRNA profiling could possibly be used in targeted screening
Paradis, Johanne; Kirova, Anna
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…
Full Text Available Abstract Background Genome scale expression profiling of human tumor samples is likely to yield improved cancer treatment decisions. However, identification of clinically predictive or prognostic classifiers can be challenging when a large number of genes are measured in a small number of tumors. Results We describe an unsupervised method to extract robust, consistent metagenes from multiple analogous data sets. We applied this method to expression profiles from five "double negative breast cancer" (DNBC (not expressing ESR1 or HER2 cohorts and derived four metagenes. We assessed these metagenes in four similar but independent cohorts and found strong associations between three of the metagenes and agent-specific response to neoadjuvant therapy. Furthermore, we applied the method to ovarian and early stage lung cancer, two tumor types that lack reliable predictors of outcome, and found that the metagenes yield predictors of survival for both. Conclusions These results suggest that the use of multiple data sets to derive potential biomarkers can filter out data set-specific noise and can increase the efficiency in identifying clinically accurate biomarkers.
Full Text Available 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.
LI Han; ZENG Qunli; WENG Yu; LU Deqiang; JIANG Huai; XU Zhengping
Extremely Low Frequency Magnetic Fields (ELF MF) has been considered as a "possible human carcinogen" by International Agency for Research on Cancer (IARC) while credible mechanisms of its carcinogenicity remain unknown. In this study, a proteomics approach was employed to investigate the changes of protein expression profile induced by ELF MF in human breast cancer cell line MCF7, in order to determine ELF MF-responsive proteins. MCF7 cells were exposed to 50 Hz, 0.4 mT ELF MF for 24 h and the changes of protein profile were examined using two dimensional electrophoresis. Up to 6 spots have been statistically significantly altered (their expression levels were changed at least 5 fold up or down) compared with sham-exposed group. 19 ones were only detected in exposure group while 19 ones were missing. Three proteins were identified by LC-IT Tandem MS as RNA binding protein regulatory subunit、Proteasome subunit beta type 7 precursor and Translationally Controlled Tumor Protein. Our finding showed that 50 Hz, 0.4 mT ELF MF alternates the protein profile of MCF7 cell and may affect many physiological functions of normal cell and 2-DE coupled with MS is a promising approach to elucidating cellular effects of electromagnetic fields.
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
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
Full Text Available Yiyi Yan, Axel Grothey Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA Abstract: Metastatic colorectal cancer (mCRC is a highly heterogeneous disease. Its treatment outcome has been significantly improved over the last decade with the incorporation of biological targeted therapies, including anti-EGFR antibodies, cetuximab and panitumumab, and VEGF inhibitors, bevacizumab, ramucirumab, and aflibercept. The identification of predictive biomarkers has further improved the survival by accurately selecting patients who are most likely to benefit from these treatments, such as RAS mutation profiling for EGFR antibodies. Regorafenib is a multikinase inhibitor currently used as late line therapy for mCRC. The molecular and genetic markers associated with regorafenib treatment response are yet to be characterized. Here, we review currently available clinical evidence of mCRC molecular profiling, such as RAS, BRAF, and MMR testing, and its role in targeted therapies with special focus on regorafenib treatment. Keywords: metastatic colon cancer, targeted therapy, molecular profiling, regorafenib
Wang, Peng; Tang, Hong; Zhang, Peng
Photodynamic therapy combining nanotechnology has shown great potential with improved therapeutic efficacy and fewer side effects. Ideal photosensitizers for cancer treatment should both have good singlet oxygen production capability and be excitable by light illuminations with deep tissue penetration. Here we report a type of hybrid photosensitizers consisting of plasmonic silver nanoparticles and photosensitizing molecules, where strong resonance coupling between the two leads to a broadened excitation profile and exceptionally high singlet oxygen production under both visible light and infrared light excitations. Our results indicate that the hybrid photosensitizers display low cytotoxicity without light illumination yet highly enhanced photodynamic inhibition efficacy against Hela cells under a broad spectrum of light illuminations including the near-infrared light, which has great implication in photodynamic therapy of deep-tissue cancers.
Gonda, David D; Cheung, Vincent J; Muller, Karra A; Goyal, Amit; Carter, Bob S; Chen, Clark C
Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q status, should facilitate accurate and reliable pathological diagnosis of LGGs.
Liu, Xiaodong; Zhang, Jianhua; Xie, Botao; Li, Hao; Shen, Jihong; Chen, Jianheng
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.
Li, Hailong; Xie, Shoupin; Liu, Xiaojun; Wu, Hongyan; Lin, Xingyao; Gu, Jing; Wang, Huping; Duan, Yongqiang
Matrine, a major alkaloid extracted from Sophora flavescens, has been reported to possess antitumor properties in several types of cancers, including gastric cancer. However, its mechanisms of action on gastric cancer remain poorly understood. Dysregulation of microRNAs, a class of small, non-coding, regulatory RNA molecules involved in gene expression, is strongly correlated with cancer. The aim of the present study was to demonstrate that matrine treatment altered miRNA expression in SGC7901 cells. Using miRCURY™ microarray analysis, we identified 128 miRNAs substantially exhibiting >2-fold expression changes in matrine-treated cells relative to their expression levels in untreated cells. RT-qPCR was used to show that the levels of 8 miRNAs whose target genes were clustered in the cell cycle pathway increased, while levels of 14 miRNAs whose target genes were clustered in the MAPK signaling pathway decreased. These results were consistent with those from the miRNA microarray experiment. Bioinformatical analysis revealed that the majority of 57 identified enrichment pathways were highly involved in tumorigenesis. In conclusion, the results demonstrated that matrine induces considerable changes in the miRNA expression profiles of SGC7901 cells, suggesting miRNA microarray combined with RT-qPCR validation and bioinformatical analysis provide a novel and promising approach to identify anticancer targets and the mechanisms of matrine involved.
Chuanding Yu; Shenhua Xu; HangZhou Mou; Zhiming Jiang; Chihong Zhu; Xianglin Liu
OBJECTIVE To study the difference of gene expression in gastric cancer (T) and normal tissue of gastric mucosa (C), and to screen for associated novel genes in gastric cancers by oligonucleotide microarrays.METHODS U133A (Affymetrix, Santa Clara, CA) gene chip was used to detect the gene expression profile difference in T and C. Bioinformatics was used to analyze the detected results.RESULTS When gastric cancers were compared with normal gastric mucosa, a total of 270 genes were found with a difference of more than 9times in expression levels. Of the 270 genes, 157 were up-regulated (Signal Log Ratio [SLR] ≥3), and 113 were down-regulated (SLR ≤-3).Using a classification of function, the highest number of gene expression differences related to enzymes and their regulatory genes (67, 24.8%),followed by signal-transduction genes (43,15.9%). The third were nucleic acid binding genes (17, 6.3%), fourth were transporter genes (15, 5.5%)and fifth were protein binding genes (12, 4.4%). In addition there were 50genes of unknown function, accounting for 18.5%. The five above mentioned groups made up 56.9% of the total gene number.CONCLUSION The 5 gene groups (enzymes and their regulatory proteins, signal transduction proteins, nucleic acid binding proteins, transporter and protein binding) were abnormally expressed and are important genes for further study in gastric cancers.
Santos, Edgardo S; Blaya, Marcelo; Raez, Luis E
Despite new developments in molecular techniques and better knowledge on lung cancer tumor biology, many genetic alterations associated with the development and progression of lung carcinogenesis still remain unclear. Although the development of targeted agents has improved response rates and survival, lung cancer has a very high mortality rate, even for early stages. Thus, there is a greater need for other mechanisms or technologies that may help us diagnose, predict, and treat patients with lung cancer in a more effective way. One of these technologies has been the use of genomics. Some of the available genomic technologies include single-nucleotide polymorphism analysis, high-throughput capillary sequencing, serial analysis of gene expression, and gene expression arrays. DNA microarray analysis is capable of discovering changes in DNA expression within the neoplastic tumor. Thus, gene expression array could help us to decipher the complexity and interaction of different oncogenic pathways and, hence, could contribute to the selection of better targeted agents on an individual basis rather than a general and nonspecific approach as it has been done for many decades. Several studies initiated a few years ago have started to produce fruitful results. Herein, we review the role of gene expression profiling in lung cancer as a diagnostic tool, predictive and prognostic biomarker, and its potential use for a "personalized" medicine in the years to come.
XU, XIAOTAO; Xiao LU; Sun, Jing; Shu, Yongqian
Background and objective Recent studies indicate that the side population (SP) which is an enriched source of cancer stem cells (CSCs) is the root cause of tumor growth and development. SP appears to be highly resistant to chemo- and radio-therapy which becomes an important factor in tumor recurrence and metastasis. The aim of this study is to determine the difference of microRNA expression profiles between SP cells and non-SP cells so as to lay necessary basis for research on the function of...
McDonald S, Watson M, Dooling DJ, Ota D, Chang LW, Bose R, Ley TJ, 18 Piwnica-Worms D, Stuart JM, Wilson RK, Mardis ER. Whole- genome analysis informs...AWARD NUMBER: W81XWH-13-1-0032 TITLE: Tumor Genomic Profiling in Breast Cancer Patients Using Targeted Massively Parallel Sequencing PRINCIPAL...THE ABOVE ADDRESS. 1. REPORT DATE I 2. REPORT TYPE 3. DATES COVERED 04-30-2015 Annual 01-01-2014 to 04-30-2015 4. TITLE AND SUBTITLE Tumor genomic
Full Text Available MicroRNA profiling represents an important first-step in deducting individual RNA-based regulatory function in a cell, tissue, or at a specific developmental stage. Currently there are several different platforms to choose from in order to make the initial miRNA profiles. In this study we investigate recently developed digital microRNA high-throughput technologies. Four different platforms were compared including next generation SOLiD ligation sequencing and Illumina HiSeq sequencing, hybridization-based NanoString nCounter, and miRCURY locked nucleic acid RT-qPCR. For all four technologies, full microRNA profiles were generated from human cell lines that represent noninvasive and invasive tumorigenic breast cancer. This study reports the correlation between platforms, as well as a more extensive analysis of the accuracy and sensitivity of data generated when using different platforms and important consideration when verifying results by the use of additional technologies. We found all the platforms to be highly capable for microRNA analysis. Furthermore, the two NGS platforms and RT-qPCR all have equally high sensitivity, and the fold change accuracy is independent of individual miRNA concentration for NGS and RT-qPCR. Based on these findings we propose new guidelines and considerations when performing microRNA profiling.
Full Text Available Jorunn Drageset,1,2 Geir Egil Eide,2,3 Elin Dysvik,4 Bodil Furnes,4 Solveig Hauge51Faculty of Health and Social Sciences, Bergen University College, Bergen, Norway; 2Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; 3Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway; 4Department of Health Studies, Faculty of Social Sciences, University of Stavanger, Stavanger, Norway; 5Faculty of Health and Social Studies and Centre for Caring Research – Southern Norway, Telemark University College, Porsgrunn, NorwayBackground: Loneliness is a significant psychosocial effect following a cancer diagnosis and may prevent people from engaging in social activities, thus creating difficulties in interpersonal relationships. This study investigated loneliness and social support among cognitively intact nursing home residents with cancer by using a quantitatively driven mixed-methods design with sequential supplementary qualitative components.Methods: The quantitative component consisted of face-to-face interviews of 60 nursing home residents (≥65 years using the one-item Loneliness Scale and the Social Provisions Scale. The supplementary psychosocial component consisted of qualitative research interviews about experiences related to loneliness with nine respondents.Results: The quantitative results indicated that reassurance of worth was associated with loneliness. The experience of loneliness was identified by the following: loneliness that was dominated by a feeling of inner pain, feeling of loss, and feeling small. Loneliness was alleviated by the following: being engaged in activities, being in contact with other people, and occupying oneself.Conclusion: Enhancing the lives of nursing home residents with cancer requires attending to the residents’ experience of loneliness and social relationships in a targeted and individualized manner. This might require screening all nursing home residents
Callesen, Anne Kjærgaard; Vach, Werner; Jørgensen, Per E
Serum protein profiling by mass spectrometry is a promising method for early detection of cancer. We have implemented a combined strategy based on matrix-assisted laser desorption ionization mass spectrometry (MALDI MS) and statistical data analysis for serum protein profiling and applied...... of nine mass spectrometric protein profiles were obtained for each serum sample. A total of 533 common peaks were defined and represented a 'reference protein profile'. Among these 533 common peaks, we identified 72 peaks exhibiting statistically significant intensity differences ( p ... and specificity. We conclude that optimized serum sample handling and mass spectrometry data acquisition strategies in combination with statistical analysis provide a viable platform for serum protein profiling in cancer diagnosis....
Hayashi, Shunsuke; Inoue, Daisuke; Sakuyama, Toshikazu; Tanifuji, Yasumasa; Moriya, Kunio; Kawakubo, Takashi
In recent years, the number of cancer patients and their families desiring palliative home-based care in Japan has increased. Subarachnoid phenol-glycerin block therapy is offered to relieve refractory anal pain in cancer patients, and to reduce the side effects of systemic administration of opioids, such as drowsiness. The effects of phenol-glycerin, which is a medicine used for neurodegenerative diseases, lasted for 1 week to 3 months. Eight patients with this manipulation showed a significant improvement in their pain level, calculated by the numerical rating scale(NRS). Five of these patients could proceed to homebased care. It is important to establish common guidelines for the management of phenol-glycerin. The participation of pharmacists in the palliative care team will contribute to further growth of home-based care.
Henderson, John C.; Neradilek, Moni B.; Moyer, Nicolas A.; Ashcraft, Kristine C.; Thirumaran, Ranjit K.
Background In polypharmacy patients under home health management, pharmacogenetic testing coupled with guidance from a clinical decision support tool (CDST) on reducing drug, gene, and cumulative interaction risk may provide valuable insights in prescription drug treatment, reducing re-hospitalization and emergency department (ED) visits. We assessed the clinical impact of pharmacogenetic profiling integrating binary and cumulative drug and gene interaction warnings on home health polypharmacy patients. Methods and findings This prospective, open-label, randomized controlled trial was conducted at one hospital-based home health agency between February 2015 and February 2016. Recruitment came from patient referrals to home health at hospital discharge. Eligible patients were aged 50 years and older and taking or initiating treatment with medications with potential or significant drug-gene-based interactions. Subjects (n = 110) were randomized to pharmacogenetic profiling (n = 57). The study pharmacist reviewed drug-drug, drug-gene, and cumulative drug and/or gene interactions using the YouScript® CDST to provide drug therapy recommendations to clinicians. The control group (n = 53) received treatment as usual including pharmacist guided medication management using a standard drug information resource. The primary outcome measure was the number of re-hospitalizations and ED visits at 30 and 60 days after discharge from the hospital. The mean number of re-hospitalizations per patient in the tested vs. untested group was 0.25 vs. 0.38 at 30 days (relative risk (RR), 0.65; 95% confidence interval (CI), 0.32–1.28; P = 0.21) and 0.33 vs. 0.70 at 60 days following enrollment (RR, 0.48; 95% CI, 0.27–0.82; P = 0.007). The mean number of ED visits per patient in the tested vs. untested group was 0.25 vs. 0.40 at 30 days (RR, 0.62; 95% CI, 0.31–1.21; P = 0.16) and 0.39 vs. 0.66 at 60 days (RR, 0.58; 95% CI, 0.34–0.99; P = 0.045). Differences in composite outcomes at
Full Text Available 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.
Wang, Fengliang; Gao, Sheng; Chen, Fei; Fu, Ziyi; Yin, Hong; Lu, Xun; Yu, Jing; Lu, Cheng
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.
Cort, A; Ozben, T; Melchiorre, M; Chatgilialoglu, C; Ferreri, C; Sansone, A
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.
Full Text Available Abstract Background Recent studies indicate that microRNAs (miRNAs are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA. Results Comparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R2 = 0.81; and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03; as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index. Conclusion In sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast
Indranil Chattopadhyay; Sujala Kapur; Joydeep Purkayastha; Rupkumar Phukan; Amal Kataki; Jagadish Mahanta; Sunita Saxena
AIM: To identify alterations in genes and molecular functional pathways in esophageal cancer in a high incidence region of India where there is a widespread use of tobacco and betel quid with fermented areca nuts.METHODS: Total RNA was isolated from tumor and matched normal tissue of 16 patients with esophageal squamous cell carcinoma. Pooled tumor tissue RNA was labeled with Cy3-dUTP and pooled normal tissue RNA was labeled with Cy5-dUTP by direct labeling method.The labeled probes were hybridized with human 10K cDNA chip and expression profiles were analyzed by Genespring GX V 7.3 (Silicon Genetics).RESULTS: Nine hundred twenty three genes were differentially expressed. Of these, 611 genes were upregulated and 312 genes were downregulated. Using stringent criteria (P ≤ 0.05 and ≥ 1.5 fold change),127 differentially expressed genes (87 upregulated and 40 downregulated) were identified in tumor tissue. On the basis of Gene Ontology, four different molecular functional pathways (MAPK pathway,G-protein coupled receptor family, ion transport activity,and serine or threonine kinase activity) were most significantly upregulated and six different molecular functional pathways (structural constituent of ribosome,endopeptidase inhibitor activity, structural constituent of cytoskeleton, antioxidant activity, acyl group transferase activity, eukaryotic translation elongation factor activity)were most significantly downregulated.CONCLUSION: Several genes that showed alterations in our study have also been reported from a high incidence area of esophageal cancer in China. This indicates that molecular profiles of esophageal cancer in these two different geographic locations are highly consistent.
Full Text Available Abstract Background Colorectal cancer (CRC is a major health concern worldwide, and recently becomes the most common cancer in Asia. The case collection of this study is one of the largest sets of CRC in Asia, and serves as representative data for investigating genomic differences between ethnic populations. We took comprehensive and high-resolution approaches to compare the clinicopathologic and genomic profiles of microsatellite instability (MSI vs. microsatellite stability (MSS in Taiwanese sporadic CRCs. Methods 1,173 CRC tumors were collected from the Taiwan population, and sequencing-based microsatellite typing assay was used to determine MSI and MSS. Genome-wide SNP array was used to detect CN alterations in 16 MSI-H and 13 MSS CRCs and CN variations in 424 general controls. Gene expression array was used to evaluate the effects of CN alterations, and quantitative PCR methods were used to replicate the findings in independent clinical samples. Results These 1,173 CRC tumors can be classified into 75 high-frequency MSI (MSI-H (6.4%, 96 low-frequency MSI (8.2% and 1,002 MSS (85.4%. Of the 75 MSI-H tumors, 22 had a BRAF mutation and 51 showed MLH1 promoter hypermethylation. There were distinctive differences in the extent of CN alterations between CRC MSS and MSI-H subtypes (300 Mb vs. 42 Mb per genome, p-value Conclusions Sporadic CRCs with MSI-H displayed distinguishable clinicopathologic features, which differ from those of MSS. Genomic profiling of the two types of sporadic CRCs revealed significant differences in the extent and distribution of CN alterations in the cancer genome. More than half of expressed genes showing CN differences can directly contribute to their expressional diversities, and the biological functions of the genes associated with CN changes in sporadic CRCs warrant further investigation to establish their possible clinical implications.
Vanessa de Albuquerque Citero
Full Text Available ABSTRACT CONTEXT: An almost 50% prevalence of psychiatric disorders among cancer patients has prompted a series of studies on consultation-liaison psychiatry. Nonetheless, there are few reports on the epidemiological factors involving comorbidity between cancer and psychiatric disorders. OBJECTIVE: To evaluate the epidemiological profile of cancer inpatients referred to the consultation-liaison psychiatric service in an oncology hospital during its first year of activity. TYPE OF STUDY: Descriptive study. SETTING: Tertiary-care teaching hospital. PARTICIPANTS: 319 patients referred 412 times to the consultation-liaison psychiatry service. PROCEDURES: From August 97 to July 98, an appraisal was made of data on all admissions registered at the Hospital do Câncer, and also all referrals registered at the consultation-liaison psychiatry service. MAIN MEASUREMENTS: The demographics and patients' clinical data, the type and flow of the request, and the evaluation conducted by the service were analyzed and comparisons with the hospital data were made. The distribution of the number of referrals was used to construct a profile of patients who had repeatedly used the service. RESULTS: Psychiatric diagnoses were found in 59% of the cases. Forty-three percent of these required medication, 18.3% needed psychotherapy, 22.1% family intervention and 20.5% guidance from the staff. Over 22.8% of the consultations were reevaluations, mainly involving younger male patients with worst prognoses. These patients required lengthier and more elaborate intervention, and had higher prevalence of depressive and behavioral disorders. CONCLUSION: A younger and mainly male population of non-surgical oncological cases was referred to the consultation-liaison psychiatric service during its first year of activity. The psychiatric disorder prevalence was higher than expected, and consisted predominantly of mood disorders. We detected a priority group, namely the reevaluated
Buhl, Ida Kappel; Gerster, Sarah; Delorenzi, Mauro
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...
David W Y Ho
Full Text Available 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
Ross, Jeffrey S; Gay, Laurie M
Targeting specific mutations that have arisen within a tumour is a promising means of increasing the efficacy of treatments, and breast cancer is no exception to this new paradigm of personalised medicine. Traditional DNA sequencing methods used to characterise clinical cancer specimens and impact treatment decisions are highly sensitive, but are often limited in their scope to known mutational hot spots. Next-generation sequencing (NGS) technologies can also test for these well-known hot spots, as well as identifying insertions and deletions, copy number changes such as ERBB2 (HER2) gene amplification, and a wide array of fusion or rearrangement events. By rapidly analysing many genes in parallel, NGS technologies can make efficient use of precious biopsy material. Comprehensive genomic profiling (CGP) by NGS can reveal targetable, clinically relevant genomic alterations that can stratify tumours by predicted sensitivity to a variety of therapies, including HER2- or MTOR-targeted therapies, immunotherapies, and other kinase inhibitors. Many clinically relevant genomic alterations would not be identified by IHC or hotspot testing, but can be detected by NGS. In addition to the most common breast carcinoma subtypes, rare subtypes analysed with CGP also harbour clinically relevant genomic alterations that can potentially direct therapy selection, illustrating that CGP is a powerful tool for guiding treatment across all breast cancer subtypes.
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
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
Januchowski, Radosław; Zawierucha, Piotr; Ruciński, Marcin; Nowicki, Michał; Zabel, Maciej
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.
... 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 ...
... 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 ...
Wang, Y; Mei, Q; Ai, Y Q; Li, R Q; Chang, L; Li, Y F; Xia, Y X; Li, W H; Chen, Y
This study aimed to identify the oncogenes associated with lung cancer based on the mRNA and single nucleotide polymorphism (SNP) profile data. The mRNA expression profile data of GSE43458 (80 cancer and 30 normal samples) and SNP profile data of GSE33355 (61 pairs of lung cancer samples and control samples) were downloaded from Gene Expression Omnibus database. Common genes between the mRNA profile and SNP profile were identified as the lung cancer oncogenes. Risk subpathways of the selected oncogenes with the SNP locus were analyzed using the iSubpathwayMiner package in R. Moreover, protein-protein interaction (PPI) network of the oncogenes was constructed using the HPRD database and then visualized using the Cytoscape. Totally, 3004 DEGs (1105 up-regulated and 1899 down-regulated) and 125 significant SNPs closely related to 174 genes in the lung cancer samples were identified. Also, 39 common genes, like PFKP (phosphofructokinase, platelet) and DGKH-rs11616202 (diacylglycerol kinase, eta) that enriched in sub-pathways such as galactose metabolism, fructose and mannose metabolism, and pentose phosphate pathway, were identified as the lung cancer oncogenes. Besides, PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1), RORA (RAR-related orphan receptor A), MAGI3 (membrane associated guanylate kinase, WW and PDZ domain containing 3), PTPRM (protein tyrosine phosphatase, receptor type, M), and BMP6 (bone morphogenetic protein 6) were the hub genes in PPI network. Our study suggested that PFKP and DGKH that enriched in galactose metabolism, fructose and mannose metabolism pathway, as well as PIK3R1, RORA, and MAGI3, may be the lung cancer oncogenes.
JÃ¶nsson, Mats; Isinger-Ekstrand, Anna; Johansson, Jan;
/losses and gene expression profiles show strong similarity between cancers in the distal esophagus and the gastroesophageal junction with frequent upregulation of CDK6 and EGFR, whereas gastric cancer displays distinct genetic changes. These data suggest that molecular diagnostics and targeted therapies can......15, 13q34, and 12q13, whereas different profiles with gains at 5p15, 7p22, 2q35, and 13q34 characterized gastric cancers. CDK6 and EGFR were identified as putative target genes in cancers of the esophagus and the gastroesophageal junction, with upregulation in one quarter of the tumors. Gains......-resolution array-based comparative genomic hybridization and 27k oligo gene expression arrays, and putative target genes were validated in an extended series. Adenocarcinomas in the distal esophagus and the gastroesophageal junction showed strong similarities with the most common gains at 20q13, 8q24, 1q21-23, 5p...
Sujatha Bhat; Ajeetkumar Patil; Lavanya Rai; Kartha, V. B.; Santhosh Chidangil
A highly objective method, High Performance Liquid Chromatography with Laser Induced Fluorescence (HPLC-LIF) technique was used to study the protein profiles of normal and cervical cancer tissue homogenates. A total of 44 samples including normal cervical biopsy samples from the hysterectomy patients and the patients suffering from different stages of the cervical cancer were recorded by HPLC-LIF and analysed by Principle Component Analysis (PCA) to get statistical information on different t...
L. M. Kurtasova
Full Text Available We have observed forty-four patients with metastatic renal cancer before and after interferon therapy. Immune markers of of peripheral blood lymphocytes were determined by flow cytometry. Activity of NAD (P-dependent dehydrogenase in blood lymphocytes was studied by means of bioluminescence technique. Changes of immune marker profiles and enzymatic activities of peripheral blood lymphocytes were found in patients with renal cancer after a course of interferon therapy.
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.
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.
Full Text Available Vittavat Termglinchan,1 Wachiraporn Wanichnopparat,1 Kulachanya Suwanwongse,1 Chunhakarn Teeyapant,1 Kanticha Chatpermporn,1 Kanchana Leerunyakul,1 Khwanruthai Chuadpia,1 Onpailin Sirimaneethum,1 Parinya Wijitworawong,1 Wattanakitch Mutirangura,1 Chatchawit Aporntewan,2 Chanida Vinayanuwattikun,3 Apiwat Mutirangura4 1Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 2Department of Mathematics and Computer Science, Faculty of Science, Chulalongkorn University, Bangkok, Thailand; 3Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok, Thailand; 4Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Background: One particularly promising component of personalized medicine in cancer treatment is targeted therapy, which aims to maximize therapeutic efficacy while minimizing toxicity. However, the number of approved targeted agents remains limited. Expression microarray data for different types of cancer are resources to identify genes that were upregulated. The genes are candidate targets for cancer-targeting agents for future anticancer research and targeted treatments. Methods and findings: The gene expression profiles of 48 types of cancer from 2,141 microarrays reported in the Gene Expression Omnibus were analyzed. These data were organized into 78 experimental groups, on which we performed comprehensive analyses using two-tailed Student's t-tests with significance set at P < 0.01 to identify genes that were upregulated compared with normal cells in each cancer type. The resulting list of significantly upregulated genes was cross-referenced with three categories of protein inhibitor targets, categorized by inhibitor type ('Targets of US Food and Drug Administration (FDA-approved anticancer drugs', 'Targets of FDA
Rapin, Nicolas; Bagger, Frederik Otzen; Jendholm, Johan
Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in iden......-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients.......Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient...... in identifying expression changes fundamental to disease etiology. Here we present a method that facilitates the comparison of any cancer sample to its nearest normal cellular counterpart, using acute myeloid leukemia (AML) as a model. We first generated a gene expression-based landscape of the normal...
Ilse Van der Auwera
Full Text Available BACKGROUND: Abnormal DNA methylation is well established for breast cancer and contributes to its progression by silencing tumor suppressor genes. DNA methylation profiling platforms might provide an alternative approach to expression microarrays for accurate breast tumor subtyping. We sought to determine whether the distinction of the inflammatory breast cancer (IBC phenotype from the non-IBC phenotype by transcriptomics could be sustained by methylomics. METHODOLOGY/PRINCIPAL FINDINGS: We performed methylation profiling on a cohort of IBC (N = 19 and non-IBC (N = 43 samples using the Illumina Infinium Methylation Assay. These results were correlated with gene expression profiles. Methylation values allowed separation of breast tumor samples into high and low methylation groups. This separation was significantly related to DNMT3B mRNA levels. The high methylation group was enriched for breast tumor samples from patients with distant metastasis and poor prognosis, as predicted by the 70-gene prognostic signature. Furthermore, this tumor group tended to be enriched for IBC samples (54% vs. 24% and samples with a high genomic grade index (67% vs. 38%. A set of 16 CpG loci (14 genes correctly classified 97% of samples into the low or high methylation group. Differentially methylated genes appeared to be mainly related to focal adhesion, cytokine-cytokine receptor interactions, Wnt signaling pathway, chemokine signaling pathways and metabolic processes. Comparison of IBC with non-IBC led to the identification of only four differentially methylated genes (TJP3, MOGAT2, NTSR2 and AGT. A significant correlation between methylation values and gene expression was shown for 4,981 of 6,605 (75% genes. CONCLUSIONS/SIGNIFICANCE: A subset of clinical samples of breast cancer was characterized by high methylation levels, which coincided with increased DNMT3B expression. Furthermore, an association was observed with molecular signatures indicative of
Cantinha, Rebeca S.; Santos, Mariana L.O.; Franca, Elvis J., E-mail: firstname.lastname@example.org, E-mail: email@example.com, E-mail: firstname.lastname@example.org [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Pessoa, Juanna G.; Melo, Ana M.M.A.; Amancio, Francisco F., E-mail: email@example.com, E-mail: firstname.lastname@example.org, E-mail: email@example.com, E-mail: firstname.lastname@example.org [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departamento de Biofisica e Radiobiologia; Oliveira Neto, Aristides M.; Melo, Jonathan A., E-mail: email@example.com, E-mail: firstname.lastname@example.org [Centro de Radioterapia de Pernambuco (CERAPE), Santo Amaro, PE (Brazil)
Cancer is a worldwide public health problem, its prevention and control are included within 16 strategic objectives of the Brazilian Ministry of Health for the period 2011-2015. Cervical cancer is the fourth most common tumor in the female population, being new 15,590 cases estimated for 2014 according to the Brazilian National Cancer Institute (INCA). Pernambuco is the fifth state with the highest number of cases of cervical cancer and the seventh in cases of endometrial ones, both estimative for 2014. The understanding of the epidemiological profile of these pathologies corroborates strategies for prevention, control and treatment. As Pernambuco has implemented the radiotherapy for cancer treatment since 1998-1999, this work encompassed the comparison of the 1998-1999 epidemiological profile of patients treated by radiotherapy for cervical and endometrial cancer in the State of Pernambuco, Brazil, with 2008-2009 profile - ten years after. Medical record of 490 patients treated at the Center of Radiotherapy of Pernambuco (CERAPE) were compiled according to the patient origin, the affected uterus region, the staging of disease, the type and cell differentiation of the tumor, the age group, and, finally, the realization of hysterectomy as part of the treatment. More than 90% of the patients were affected by cervical cancer in the two investigated periods. For the interval of 1998-1999 the proportion of patients submitted to hysterectomy was quite higher compared to those after ten years. The results also showed a change in the origin of the patients, in which, in 1999, most of the patients were from the capital and the metropolitan area, while, after ten years, patients were mostly from the interior of the State. There was a predominance of squamous cell type tumors in both periods evaluated. For the 1998-1999 interval, tumors were stage 2, moderately differentiated type. Differently, the tumors were mostly stage 3, not differentiated type, for the 2008-2009 period
Full Text Available Alessandra Gorini,1,2 Ketti Mazzocco,1,2 Sara Gandini,2 Elisabetta Munzone,2 Gordon McVie,2 Gabriella Pravettoni1,2 1Department of Health Science, University of Milan, Milan, Italy; 2European Institute of Oncology, Milan, Italy 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
Kogita, Akihiro; Yoshioka, Yasumasa; Sakai, Kazuko; Togashi, Yosuke; Sogabe, Shunsuke; Nakai, Takuya; Okuno, Kiyotaka; Nishio, Kazuto
Intra- and inter-tumor heterogeneity may hinder personalized molecular-target treatment that depends on the somatic mutation profiles. We performed mutation profiling of formalin-fixed paraffin embedded tumors of multi-regional colon cancer and characterized the consequences of intra- and inter-tumor heterogeneity and metastasis using targeted re-sequencing. We performed targeted re-sequencing on multiple spatially separated samples obtained from multi-regional primary colon carcinoma and associated metastatic sites in two patients using next-generation sequencing. In Patient 1 with four primary tumors (P1-1, P1-2, P1-3, and P1-4) and one liver metastasis (H1), mutually exclusive pattern of mutations was observed in four primary tumors. Mutations in primary tumors were identified in three regions; KARS (G13D) and APC (R876*) in P1-2, TP53 (A161S) in P1-3, and KRAS (G12D), PIK3CA (Q546R), and ERBB4 (T272A) in P1-4. Similar combinatorial mutations were observed between P1-4 and H1. The ERBB4 (T272A) mutation observed in P1-4, however, disappeared in H1. In Patient 2 with two primary tumors (P2-1 and P2-2) and one liver metastasis (H2), mutually exclusive pattern of mutations were observed in two primary tumors. We identified mutations; KRAS (G12V), SMAD4 (N129K, R445*, and G508D), TP53 (R175H), and FGFR3 (R805W) in P2-1, and NRAS (Q61K) and FBXW7 (R425C) in P2-2. Similar combinatorial mutations were observed between P2-1 and H2. The SMAD4 (N129K and G508D) mutations observed in P2-1, however, were nor detected in H2. These results suggested that different clones existed in primary tumors and metastatic tumor in Patient 1 and 2 likely originated from P1-4 and P2-1, respectively. In conclusion, we detected the muti-clonalities between intra- and inter-tumors based on mutational profiling in multi-regional colon cancer using next-generation sequencing. Primary region from which metastasis originated could be speculated by mutation profile. Characterization of inter- and
Oxygen - home use; COPD - home oxygen; Chronic obstructive airways disease - home oxygen; Chronic obstructive lung disease - home oxygen; Chronic bronchitis - home oxygen; Emphysema - home oxygen; Chronic respiratory ...
Thomas A. Dunn; Helen L. Fedor; Angelo M. De Marzo; Jun Luo
The contemporary problem of prostate cancer overtreatment can be partially attributed to the diagnosis of potentially indolent prostate cancers that pose low risk to aged men,and lack of sufficiently accurate risk stratification methods to reliably seek out men with indolent diseases.Since progressive acquisition and accumulation of genomic alterations,both genetic and epigenetic,is a defining feature of all human cancers at different stages of disease progression,it is hypothesized that RNA and DNA alterations characteristic of indolent prostate tumors may be different from those previously characterized in the setting of clinically significant prostate cancer.Approaches capable of detecting such alterations on a genome-wide level are the most promising.Such analysis may uncover molecular events defining early initiating stages along the natural history of prostate cancer progression,and ultimately lead to rational development of risk stratification methods for identification of men who can safely forego treatment.However,defining and characterizing indolent prostate cancer in a clinically relevant context remains a challenge,particularly when genome-wide approaches are employed to profile formalin-fixed paraffin-embedded (FFPE) tissue specimens.Here,we provide the conceptual basis underlying the importance of understanding indolent prostate cancer from molecular profiling studies,identify the key hurdles in sample acquisition and variables that affect molecular data derived from FFPE tissues,and highlight recent progresses in efforts to address these technical challenges.
MA Ding; ZHANG You-yi; GUO Yan-li; LI Zi-jian; GENG Li
Background Cervical cancer is one of the most common malignant tumors in women.This study was designed to explore the expression profiles of microRNAs (miRNAs) and mRNAs and the gene regulation network in cervical tumorigenesis and to find candidate molecular markers and key tumorigenic genes in cervical cancer.Methods miRNAs and mRNAs expression microarrays were used to detect the expression of miRNAs and mRNAs in normal and cancer cervical tissues.TargetScan 5.0 database (UK) was used to predict the target genes of the miRNAs,analyze their intersection with differentially expressed mRNAs and negatively correlate the intersection with miRNAs.Bioinformatic approaches were used to analyze functions and pathways of the target genes and establish miRNA-gene network.Results Twenty-nine miRNAs and 2036 mRNAs were differentially expressed in normal and cervical tumor tissues.Among them,13 miRNAs and 754 mRNAs were up-regulated in cervical tumor tissues and 16 miRNAs and 1282 RNA were down-regulated.The 327 target genes negatively related to miRNAs in the intersection were involved in functions and signal pathways.Down-regulated miRNAs targeted genes and up-regulated miRNAs targeted genes were involved in 415 and 163 functions,respectively,and in 37 and 17 significant pathways,respectively (P ＜0.05,false discovery rate (FDR) ＜0.05).We constructed the miRNAs-gene network and found that hsa-miR-15a,hsa-miR-106b and hsa-miR-20b were key nodes in the network.Conclusions The differentially expressed miRNAs and mRNAs in cervical cancer and related miRNA-gene network have been identified.They play important roles in cervical tumorigenesis and are involved in many important biological functions and signal transduction pathways.These findings lay a foundation for research on the molecular mechanism of miRNAs in the pathogenesis of cervical cancer.
Won, Jennifer R; Gao, Dongxia; Chow, Christine; Cheng, Jinjin; Lau, Sherman Y H; Ellis, Matthew J; Perou, Charles M; Bernard, Philip S; Nielsen, Torsten O
Gene expression profiling of breast cancer delineates a particularly aggressive subtype referred to as 'basal-like', which comprises ∼15% of all breast cancers, afflicts younger women and is refractory to endocrine and anti-HER2 therapies. Immunohistochemical surrogate definitions for basal-like breast cancer, such as the clinical ER/PR/HER2 triple-negative phenotype and models incorporating positive expression for CK5 (CK5/6) and/or EGFR are heavily cited. However, many additional biomarkers for basal-like breast cancer have been described in the literature. A parallel comparison of 46 proposed immunohistochemical biomarkers of basal-like breast cancer was performed against a gene expression profile gold standard on a tissue microarray containing 42 basal-like and 80 non-basal-like breast cancer cases. Ki67 and PPH3 were the most sensitive biomarkers (both 92%) positively expressed in the basal-like subtype, whereas CK14, IMP3 and NGFR were the most specific (100%). Among biomarkers surveyed, loss of INPP4B (a negative regulator of phosphatidylinositol signaling) was 61% sensitive and 99% specific with the highest odds ratio (OR) at 108, indicating the strongest association with basal-like breast cancer. Expression of nestin, a common marker of neural progenitor cells that is also associated with the triple-negative/basal-like phenotype and poor breast cancer prognosis, possessed the second highest OR at 29 among the 46 biomarkers surveyed, as well as 54% sensitivity and 96% specificity. As a positively expressed biomarker, nestin possesses technical advantages over INPP4B that make it a more ideal biomarker for identification of basal-like breast cancer. The comprehensive immunohistochemical biomarker survey presented in this study is a necessary step for determining an optimized surrogate immunopanel that best defines basal-like breast cancer in a practical and clinically accessible way.
Hvid, Thine; Lindegaard, Birgitte; Winding, Kamilla;
AIM: Physical activity after prostate cancer diagnosis has been shown to reduce the risk of disease progression. Here, we aimed to evaluate the effect of a 2-year home-based endurance training intervention on body composition, biomarkers levels, and prostate-specific antigen (PSA) doubling time...... as a surrogate end-point for progressing disease. METHODS: Out-clinic patients with either biochemical recurrence following radical prostatectomy or patients managed on active surveillance were randomized to either 24 months (3 times/week) of home-based endurance training or usual care. Aerobic fitness, body...... composition, insulin sensitivity, and biomarkers were measured at 0, 6, and 24 months of intervention. PSA doubling time (PSADT) was calculated based on monthly PSA measurements. RESULTS: Twenty-five patients were enrolled, and 19 patients completed the study. PSADT increased in the training group from 28...
... cancer Non-Hodgkin lymphoma Ovarian cancer Pancreatic cancer Testicular cancer Thyroid cancer Uterine cancer Symptoms Symptoms of cancer ... tumor Obesity Pancreatic cancer Prostate cancer Stomach cancer Testicular cancer Throat or larynx cancer Thyroid cancer Patient Instructions ...
Rajani Rai; Mallika Tewari; Mohan Kumar; Tej Bali Singh; Hari S Shukla
BACKGROUND: Regulatorypeptidereceptorshaveattractedthe interest of oncologists as a new promising approach for cancer pathology, imaging and therapy. Although cholecystokinin (CCK) is a potent modulator of gallbladder contractility and plays a potential role in pancreatic carcinogenesis through CCK type-A receptor (CCKAR), its role in gallbladder cancer (GBC) is still unknown and immunohistochemical detection of CCKAR in the gallbladder has not yet been reported. This novel case-control study aimed to investigate the expression profile of CCKAR in GBC and gallstone disease (GSD). METHODS: This study included 162 samples of gallbladder: 94 fromGBCand68fromGSD.ExpressionofCCKARwasanalyzed by immunohistochemistry and immunoblotting. The results were statistically correlated with disease history including age, sex, presenceofgallstone,stageanddifferentiation. RESULTS: CCKAR was positive in 30/68 (44.1%) of GSD and 72/94 (76.6%) of GBC samples. Fifty-one of the 72 (70.8%) CCKAR-positive GBC samples showed over-expression. Interestingly, consistent results also appeared in the immuno-blotting study. CONCLUSIONS: CCKARexpressionwassignificantlyincreased in GBC compared to GSD. Moreover, CCKAR expression was associated with the degree of tumor differentiation, i.e., less expression in poorly-differentiated tumors. Thus, it has future prognostic and therapeutic implications in the management of GBC.
吕桂泉; 许沈华; 牟瀚舟; 朱赤红; 羊正炎; 高永良; 楼洪坤; 刘祥麟; 杨文; 程勇
To study the gene expression of high metastatic human ovarian carcinoma cell line (HO-8910PM) and to screen for novel metastasis- associated genes by cDNA microarray. Methods: The cDNA was retro-transcribed from equal quantity mRNA derived from tissues of highly metastatic ovarian carcinoma cell line and normal ovarian, and was labeled with Cy5 and Cy3 fluorescence as probes. The mixed probes were hybridized with BioDoor 4096 double dot human whole gene chip. The chip was scanned by scanArray 3000 laser scanner. The acquired image was analyzed by ImaGene 3.0 software. Results: By applying the cDNA microarray we found: A total of 323 genes whose expression level were 3 times higher or lower in HO-8910PM cell than normal ovarian epithelium cell were screened out, with 71 higher and 252 lower respectively. Among these 10 were new genes. 67 genes showed expression difference bigger than 6 times between HO-8910PM cell and normal ovarian epithelium cell, among these genes 12 were higher, 55 lower, and two new genes were found. Conclusion: cDNA microarray technique is effective in screening the differentially expressed genes between human ovarian cancer cell line (HO-8910PM) and normal ovarian epithelium cell. Using the cDNA microarray to analyze of human ovarian cancer cell line gene expression profile difference will help the gene diagnosis, treatment and protection.
Selnaes, K.M.; Gribbestad, I.S.; Bertilsson, H.; Wright, A.; Angelsen, A.; Heerschap, A.; Tessem, M.B.
MR metabolic profiling of the prostate is promising as an additional diagnostic approach to separate indolent from aggressive prostate cancer. The objective of this study was to assess the relationship between the Gleason score and the metabolic biomarker (choline + creatine + spermine)/citrate (CCS
Ana Carolina de Castro Mendonça Queiroz
Full Text Available Persons in palliative care develop pressure ulcers (PU as death approaches, but the extent of the problem is still unknown. The objectives were to identify the prevalence of pressure ulcers in people with cancer in palliative home care, compare the socio-demographic and clinical profile of patients with and without pressure ulcers, and analyze the characteristics of the ulcers. This descriptive, cross-sectional study included 64 people with advanced cancer in palliative home care. Twelve of them (18.8% had PU, of whom 75.0% were men. The participants had one to three PU, amounting to 19 lesions, 89.4% of those developed at home and 47.4% at stage 3. The presence of PU was higher among those who had a history of previous wound. PU consisted of a significant event occurring in the studied population, indicating that preventive measures should be included in the home palliative care health team.
Dienstmann, Rodrigo; Serpico, Danila; Rodon, Jordi; Saura, Cristina; Macarulla, Teresa; Elez, Elena; Alsina, Maria; Capdevila, Jaume; Perez-Garcia, Jose; Sánchez-Ollé, Gessamí; Aura, Claudia; Prudkin, Ludmila; Landolfi, Stefania; Hernández-Losa, Javier; Vivancos, Ana; Tabernero, Josep
Clinical experience increasingly suggests that molecular prescreening and biomarker enrichment strategies in phase I trials with targeted therapies will improve the outcomes of patients with cancer. In keeping with the exigencies of a personalized oncology program, tumors from patients with advanced chemorefractory colorectal cancer were analyzed for specific aberrations (KRAS/BRAF/PIK3CA mutations, PTEN and pMET expression). Patients were subsequently offered phase I trials with matched targeted agents (MTA) directed at the identified anomalies. During 2010 and 2011, tumor molecular analysis was conducted in 254 patients: KRAS mutations (80 of 254, 31.5%), BRAF mutations (24 of 196, 12.2%), PIK3CA mutations (15 of 114, 13.2%), KRAS and PIK3CA mutations (9 of 114, 7.9%), low PTEN expression (97 of 183, 53.0%), and high pMET expression (38 of 64, 59.4%). In total, 68 patients received 82 different MTAs: phosphoinositide 3-kinase (PI3K) pathway inhibitor (if PIK3CA mutation, n = 10; or low PTEN, n = 32), PI3K pathway inhibitor plus MEK inhibitor (if KRAS mutation, n = 10; or BRAF mutation, n = 1), second-generation anti-EGF receptor monoclonal antibodies (if wild-type KRAS, n = 11), anti-hepatocyte growth factor monoclonal antibody (if high pMET, n = 10), mTOR inhibitor plus anti-insulin-like growth factor-1 receptor monoclonal antibody (if low PTEN, n = 5), and BRAF inhibitor (if BRAF mutation, n = 3). Median time-to-treatment failure on MTA was 7.9 versus 16.3 weeks for their prior systemic antitumor therapy (P 16 weeks in 10 cases (12.2%). These results suggest that matching chemorefractory patients with colorectal cancer with targeted agents in phase I trials based on the current molecular profile does not confer a significant clinical benefit.
Hodgson, Nancy A; Lafferty, Doreen
Objective. The purpose of this pilot study was to investigate and compare the effects of reflexology and Swedish massage therapy on physiologic stress, pain, and mood in older cancer survivors residing in nursing homes. Methods. An experimental, repeated-measures, crossover design study of 18 nursing home residents aged 75 or over and diagnosed with solid tumor in the past 5 years and following completion of cancer treatments. The intervention tested was 20 minutes of Swedish Massage Therapy to the lower extremities, versus 20 minute Reflexology, using highly specified protocols. Pre- and post-intervention levels of salivary cortisol, observed affect, and pain were compared in the Swedish Massage Therapy and Reflexology conditions. Results. Both Reflexology and Swedish Massage resulted in significant declines in salivary cortisol and pain and improvements in mood. Conclusions. Preliminary data suggest that studies of Swedish Massage Therapy and Reflexology are feasible in this population of cancer survivors typically excluded from trials. Both interventions were well tolerated and produced measurable improvements in outcomes. Further research is needed to explore the mechanisms underlying the potential benefits of these CAM modalities in this patient population.
Nancy A. Hodgson
Full Text Available Objective. The purpose of this pilot study was to investigate and compare the effects of reflexology and Swedish massage therapy on physiologic stress, pain, and mood in older cancer survivors residing in nursing homes. Methods. An experimental, repeated-measures, crossover design study of 18 nursing home residents aged 75 or over and diagnosed with solid tumor in the past 5 years and following completion of cancer treatments. The intervention tested was 20 minutes of Swedish Massage Therapy to the lower extremities, versus 20 minute Reflexology, using highly specified protocols. Pre- and post-intervention levels of salivary cortisol, observed affect, and pain were compared in the Swedish Massage Therapy and Reflexology conditions. Results. Both Reflexology and Swedish Massage resulted in significant declines in salivary cortisol and pain and improvements in mood. Conclusions. Preliminary data suggest that studies of Swedish Massage Therapy and Reflexology are feasible in this population of cancer survivors typically excluded from trials. Both interventions were well tolerated and produced measurable improvements in outcomes. Further research is needed to explore the mechanisms underlying the potential benefits of these CAM modalities in this patient population.
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Midorikawa, Yasuhiko; Suzushino, Seiko; Tamotsu, Kiyokazu
We conducted home care and home palliative care from the department of home care. We provided home care services to 190 patients(105 men, 85 women)in October 2013. Their average age was 78.7(range: 32-102)years old, and home care had been underway from 1 day to 8 years, 10 months. Among all participants, 168(88.4%)suffered from malignant diseases, 168 patients had died, and over half of deceased patients(88 out of 168)had died at home. We used opioids for control of cancer pain, carried out home parenteral nutrition(HPN), home enteral nutrition(HEN), percutaneous endoscopic gastrostomy( PEG), and removed pleural effusion and ascites during home care. In order to facilitate the practice of palliative care by the palliative care team, which consists of various medical staff in the hospital, we are giving high priority to education and enlightenment in the hospital. To provide enlightenment, education, and cooperation between regional home care and home palliative care, we are also conducting educational lectures in the regional party of the Iwaki city medical associate, and providing combined educational-medical training for home care and home palliative care by various medical staff.
Devik, Siri Andreassen; Hellzen, Ove; Enmarker, Ingela
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.
Siri Andreassen Devik
Full Text Available 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.
Full Text Available Abstract Background UbcH10 participates in proper metaphase to anaphase transition, and abrogation of UbcH10 results in the premature separation of sister chromatids. To assess the potential role of UbcH10 in colon cancer progression, we analyzed the clinicopathological relevance of UbcH10 in colon cancer. Methods We firstly screened the expression profile of UbcH10 in various types of cancer tissues as well as cell lines. Thereafter, using the colon cancer cells line, we manipulated the expression of UbcH10 and evaluated the cell cycle profile and cellular proliferations. Furthermore, the clinicopathological significance of UbcH10 was immunohistologically evaluated in patients with colon cancer. Statistical analysis was performed using the student's t-test and Chi-square test. Results Using the colon cancer cells, depletion of UbcH10 resulted in suppression of cellular growth whereas overexpression of UbcH10 promoted the cellular growth and oncogenic cellular growth. Mitotic population was markedly alternated by the manipulation of UbcH10 expression. Immunohistochemical analysis indicated that UbcH10 was significantly higher in colon cancer tissue compared with normal colon epithelia. Furthermore, the clinicopathological evaluation revealed that UbcH10 was associated with high-grade histological tumors. Conclusion The results show the clinicopathological significance of UbcH10 in the progression of colon cancer. Thus UbcH10 may act as a novel biomarker in patients with colon cancer.
Yang, Yong; Li, Hui; Hou, Shengcai; Hu, Bin; Liu, Jie; Wang, Jun
Cisplatin-based chemotherapy is the standard therapy used for the treatment of several types of cancer. However, its efficacy is largely limited by the acquired drug resistance. To date, little is known about the RNA expression changes in cisplatin-resistant cancers. Identification of the RNAs related to cisplatin resistance may provide specific insight into cancer therapy. In the present study, expression profiling of 7 cancer cell lines was performed using oligonucleotide microarray analysis data obtained from the GEO database. Bioinformatic analyses such as the Gene Ontology (GO) and KEGG pathway were used to identify genes and pathways specifically associated with cisplatin resistance. A signal transduction network was established to identify the core genes in regulating cancer cell cisplatin resistance. A number of genes were differentially expressed in 7 groups of cancer cell lines. They mainly participated in 85 GO terms and 11 pathways in common. All differential gene interactions in the Signal-Net were analyzed. CTNNB1, PLCG2 and SRC were the most significantly altered. With the use of bioinformatics, large amounts of data in microarrays were retrieved and analyzed by means of thorough experimental planning, scientific statistical analysis and collection of complete data on cancer cell cisplatin resistance. In the present study, a novel differential gene expression pattern was constructed and further study will provide new targets for the diagnosis and mechanisms of cancer cisplatin resistance.
Hansen, Ellen Kathrine; Olesen, Gitte Gylling Hammershøj; Mullins, Michael
The article places focus on how smart technologies integrated in a one family- home and particular the window offer unique challenges and opportunities for designing buildings with the best possible environments for people and nature. Toward an interdisciplinary approach, we address the interaction...... between daylight defined in technical terms and daylight defined in aesthetic, architectural terms. Through field-tests of a Danish carbon-neutral home and an analysis of five key design parameters, we explore the contradictions and potentials in smart buildings, using the smart window as example of how...... to the energy design is central. The study illuminates an approach of the design of smart houses as living organisms by connecting technology with the needs of the occupants with the power and beauty of daylight....
Cho, Nancy L., E-mail: email@example.com [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Lin, Chi-Iou [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Du, Jinyan [Broad Institute, Massachusetts Institute of Technology, Cambridge, MA 02142 (United States); Whang, Edward E. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States); Ito, Hiromichi [Department of Surgery, Michigan State University, Lansing, MI 48912 (United States); Moore, Francis D.; Ruan, Daniel T. [Department of Surgery, Brigham and Women' s Hospital, Boston, MA 02115 (United States)
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
Biji M Sankaran
Full Text Available Aim: To report the prevalence and outcomes of pressure ulcers (PU seen in a cohort of cancer patients requiring home-based palliative care. Materials and Methods: All patients referred for home care were eligible for this prospective observational study, provided they were living within a distance of 35 km from the institute and gave informed consent. During each visit, caregivers were trained and educated for providing nursing care for the patient. Dressing material for PU care was provided to all patients free of cost and care methods were demonstrated. Factors influencing the occurrence and healing of PUs were analyzed using logistic regression. Duration for healing of PU was calculated using the Kaplan Meier method. P < 0.05 are taken as significant. Results: Twenty-one of 108 (19.4% enrolled patients had PU at the start of homecare services. None of the patients developed new PU during the course of home care. Complete healing of PU was seen in 9 (42.9% patients. The median duration for healing of PU was found to be 56 days. Median expenditure incurred in patients with PU was Rs. 2323.40 with a median daily expenditure of Rs. 77.56. Conclusions: The present model of homecare service delivery was found to be effective in the prevention and management of PUs. The high prevalence of PU in this cohort indicates a need for greater awareness for this complication. Clinical Trial Registry Number: CTRI/2014/03/004477
Full Text Available Introduction & Objective: Reducing in muscle strength of the shoulder girdle is a side effect of breast cancer treatment. The aim of this study was to determine the effect of 4 weeks of resistance and mobility training on the shoulder girdle strength of women with breast cancer. Materials & Methods: In this randomized clinical trial study twenty-seven postmenopausal women with breast cancer (mean age, 51±5.96 years, (mean height, 158.08±7.2 cm, (mean weight, 63.08±11.06 kg who underwent surgery, chemotherapy and radiation therapy, were purposefully selected and divided into two groups of intervention and control. Intervention group performed 4 weeks (4 sessions per week of resistance training with flex-band and stretch training at home, but the control group did not participate in any sports or physical program. Muscle strength before and after intervention was measured using a handheld dynamometer. The data were analyzed using ANCOVA. Results: Significant differences were seen between intervention and control groups in shoulder flexion, scapula abduction and upward rotation, shoulder internal rotation, shoulder external rotation, shoulder horizontal adduction and scapula depression and adduction strength, as all strength variables increased after 4 weeks exercise. Conclusion: Since strength plays an important role in ADL performance and shoulder girdle function in breast cancer survivors, it seems that muscle strength improvement following combined home based exercise program can help patients after treatment to easier and faster rehabilitation. (Sci J Hamadan Univ Med Sci 2014; 21 (3: 185-195
Full Text Available 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.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.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.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 improve the standard of care for all
Kwiatkowski, Przemysław; Wierzbicki, Piotr; Kmieć, Andrzej; Godlewski, Janusz
Colorectal cancer is the most common cancer of the gastrointestinal tract. It is considered as a biological model of a certain type of cancerogenesis process in which progression from an early to late stage adenoma and cancer is accompanied by distinct genetic alterations. Clinical and pathological parameters commonly used in clinical practice are often insufficient to determine groups of patients suitable for personalized treatment. Moreover, reliable molecular markers with high prognostic value have not yet been determined. Molecular studies using DNA-based microarrays have identified numerous genes involved in cell proliferation and differentiation during the process of cancerogenesis. Assessment of the genetic profile of colorectal cancer using the microarray technique might be a useful tool in determining the groups of patients with different clinical outcomes who would benefit from additional personalized treatment. The main objective of this study was to present the current state of knowledge on the practical application of gene profiling techniques using microarrays for determining diagnosis, prognosis and response to treatment in colorectal cancer.
Full Text Available Abstract Background δ-Catenin is a unique member of β-catenin/armadillo domain superfamily proteins and its primary expression is restricted to the brain. However, δ-catenin is upregulated in human prostatic adenocarcinomas, although the effects of δ-catenin overexpression in prostate cancer are unclear. We hypothesized that δ-catenin plays a direct role in prostate cancer progression by altering gene profiles of cell cycle regulation and cell survival. Results We employed gene transfection and small interfering RNA to demonstrate that increased δ-catenin expression promoted, whereas its knockdown suppressed prostate cancer cell viability. δ-Catenin promoted prostate cancer cell colony formation in soft agar as well as tumor xenograft growth in nude mice. Deletion of either the amino-terminal or carboxyl-terminal sequences outside the armadillo domains abolished the tumor promoting effects of δ-catenin. Quantitative RT2 Profiler™ PCR Arrays demonstrated gene alterations involved in cell cycle and survival regulation. δ-Catenin overexpression upregulated cyclin D1 and cdc34, increased phosphorylated histone-H3, and promoted the entry of mitosis. In addition, δ-catenin overexpression resulted in increased expression of cell survival genes Bcl-2 and survivin while reducing the cell cycle inhibitor p21Cip1. Conclusion Taken together, our studies suggest that at least one consequence of an increased expression of δ-catenin in human prostate cancer is the alteration of cell cycle and survival gene profiles, thereby promoting tumor progression.
... Graphics Infographic Stay Informed Cancer Home What Is Lung Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet ... cancer starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may ...
Ji Soo Choi
Full Text Available The purpose of this study was to determine whether metabolic profiling of core needle biopsy (CNB samples using high-resolution magic angle spinning (HR-MAS magnetic resonance spectroscopy (MRS could be used for predicting pathologic response to neoadjuvant chemotherapy (NAC in patients with locally advanced breast cancer. After institutional review board approval and informed consent were obtained, CNB tissue samples were collected from 37 malignant lesions in 37 patients before NAC treatment. The metabolic profiling of CNB samples were performed by HR-MAS MRS. Metabolic profiles were compared according to pathologic response to NAC using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA. Various metabolites including choline-containing compounds were identified and quantified by HR-MAS MRS in all 37 breast cancer tissue samples obtained by CNB. In univariate analysis, the metabolite concentrations and metabolic ratios of CNB samples obtained with HR-MAS MRS were not significantly different between different pathologic response groups. However, there was a trend of lower levels of phosphocholine/creatine ratio and choline-containing metabolite concentrations in the pathologic complete response group compared to the non-pathologic complete response group. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the pathologic response groups. This study showed OPLS-DA multivariate analysis using metabolic profiles of pretreatment CNB samples assessed by HR- MAS MRS may be used to predict pathologic response before NAC, although we did not identify the metabolite showing statistical significance in univariate analysis. Therefore, our preliminary results raise the necessity of further study on HR-MAS MR metabolic profiling of CNB samples for a large number of cancers.
Rognum Torleiv O
Full Text Available Abstract Background Tumor cell lines are commonly used as experimental tools in cancer research, but their relevance for the in vivo situation is debated. In a series of 11 microsatellite stable (MSS and 9 microsatellite unstable (MSI colon cancer cell lines and primary colon carcinomas (25 MSS and 28 MSI with known ploidy stem line and APC, KRAS, and TP53 mutation status, we analyzed the promoter methylation of the following genes: hMLH1, MGMT, p16INK4a (CDKN2A α-transcript, p14ARF (CDKN2A β-transcript, APC, and E-cadherin (CDH1. We compared the DNA methylation profiles of the cell lines with those of the primary tumors. Finally, we examined if the epigenetic changes were associated with known genetic markers and/or clinicopathological variables. Results The cell lines and primary tumors generally showed similar overall distribution and frequencies of gene methylation. Among the cell lines, 15%, 50%, 75%, 65%, 20% and 15% showed promoter methylation for hMLH1, MGMT, p16INK4a, p14ARF, APC, and E-cadherin, respectively, whereas 21%, 40%, 32%, 38%, 32%, and 40% of the primary tumors were methylated for the same genes. hMLH1 and p14ARF were significantly more often methylated in MSI than in MSS primary tumors, whereas the remaining four genes showed similar methylation frequencies in the two groups. Methylation of p14ARF, which indirectly inactivates TP53, was seen more frequently in tumors with normal TP53 than in mutated samples, but the difference was not statistically significant. Methylation of p14ARF and p16INK4a was often present in the same primary tumors, but association to diploidy, MSI, right-sided location and female gender was only significant for p14ARF. E-cadherin was methylated in 14/34 tumors with altered APC further stimulating WNT signaling. Conclusions The present study shows that colon cancer cell lines are in general relevant in vitro models, comparable with the in vivo situation, as the cell lines display many of the same
Full Text Available OBJECTIVE: Triple-negative breast cancer (TNBC patients with truly chemosensitive disease still represent a minority among all TNBC patients. The aim of the present study is to identify microRNAs (miRNAs that correlate with TNBC chemoresistance. METHODS: In this study, we conducted miRNAs profile comparison between triple-negative breast cancer (TNBCs and normal breast tissues by microRNA array. Quantitative real-time PCR (qRT-PCR was utilized to confirm the specific deregulated miRNAs change trend. We used starBase 2.1 and GOrilla to predict the potential targets of the specific miRNAs. Cells viability and apoptosis assays were employed to determine the effect of alteration of the specific miRNAs in TNBC cells on the chemosensitivity. RESULTS: We identified 11 specific deregulated miRNAs, including 5 up-regulated miRNAs (miR-155-5p, miR-21-3p, miR-181a-5p, miR-181b-5p, and miR-183-5p and 6 down-regulated miRNAs (miR-10b-5p, miR-451a, miR-125b-5p, miR-31-5p, miR-195-5p and miR-130a-3p. Thereafter, this result was confirmed by qRT-PCR. We predicted the potential targets of the candidate miRNAs and found that they are involved in cancer-associated pathways. For the first time, we found that miR-130a-3p and miR-451a were down-regulated in TNBC. 9 of the 11 specific deregulated miRNAs were found to be associated with chemoresistance. In vitro assays, we found that up-regulation of either miR-130a-3p or miR-451a in MDA-MB-231 cells significantly changed the cells sensitivity to doxorubicin. The results suggest that TNBC chemotherapy might be affected by a cluster of miRNAs. CONCLUSION: The abnormal expression miRNAs in TNBC are mainly chemoresistance related. This might be part of reason that TNBC likely to evade from chemotherapy resulting in early relapse and high risk of death. To alter their expression status might be a potential therapeutic strategy to improve the outcome of chemotherapy for TNBC patients.
Kinoshita, Shoji; Inoue, Daisuke; Sakuyama, Toshikazu; Yoshizawa, Akitaka; Nagasaki, Eijiroh; Arakawa, Yasuhiro; Uwagawa, Tadashi; Kobayashi, Kazuma; Kobayashi, Tadashi; Saitoh, Nobuhiro; Aiba, Keisuke
We report the case of a patient with a stage IV b pancreatic cancer in which epidural/subcutaneous reservoir therapy was effective for pain control. However, a catheter-related infection caused by methicillin-resistant Staphylococcus aureus (MRSA)was occurred. In recent years, the number of cancer patients desiring palliative home-based care in Japan has increased. Epidural/subcutaneous reservoir therapy is often offered to relieve refractory pain, and to reduce the side effects of systemic administration of opioids, such as drowsiness, in homecare patients. We believe that this patient may have been able to continue home-based care if the catheter-related infection did not occur, because a significant improvement was calculated in the pain level by the numerical rating scale(NRS)observed. It is important to establish and share common strict guidelines between hospital doctors and general practitioners for the management of the subcutaneous catheter and reservoir therapy in order to prevent catheter-related infections over a long period.
Kenny, Paraic A; Lee, Genee Y; Myers, Connie A;
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...
Karolin Trautmann; Christine Steudel; Dana Grossmann; Daniela Aust; Gerhard Ehninger; Stephan Miehlke; Christian Thiede
AIM: Gene expression profiling provides an unique opportunity to gain insight into the development of different types of gastric cancer. Tumor sample heterogeneity is thought to decrease the sensitivity and tumor specificity of microarray analysis. Thus, microdissection and preamplification of RNA is frequently performed. However, this technique may also induce considerable changes to the expression profile. To assess the effect of gastric tumor heterogeneity on expression profiling results, we measured the variation in gene expression within the same gastric cancer sample by performing a gene chip analysis with two RNA preparations extracted from the same tumor specimen.METHODS: Tumor samples from six intestinal T2 gastric tumors were dissected under liquid nitrogen and RNA was prepared from two separate tumor fragments. Each extraction was individually processed and hybridized to an Affymetrix U133A gene chip covering approximately 18 000 human gene transcripts. Expression profiles were analyzed using Microarray Suite 5.0 (Affymetrix) and GeneSpring 6.0 (Silicon Genetics).RESULTS: All gastric cancers showed little variance in expression profiles between different regions of the same tumor sample. In this case, gene chips displayed mean pair wise correlation coefficients of 0.94±0.02 (mean±SD),compared to values of 0.61±0.1 for different tumor samples. Expression of the variance between the two expression profiles as a percentage of "total change"(Affymetrix) revealed a remarkably low average value of 1.18±0.78 for comparing fragments of the same tumor sample.In contrast, comparison of fragments from different tumors revealed a percentage of 24.4±4.5.CONCLUSION: Our study indicates a low degree of expression profile variability within gastric tumor samples isolated from one patient. These data suggest that tumor tissue heterogeneity is not a dominant source of error for microarray analysis of larger tumor samples, making total RNA extraction an appropriate
Juric, Dejan; Sale, Sanja; Hromas, Robert A.; Yu, Ron; Wang, Yan; Duran, George E.; Tibshirani, Robert; Einhorn, Lawrence H.; Sikic, Branimir I.
Germ cell tumors (GCTs) of the testis are the predominant cancer among young men. We analyzed gene expression profiles of 50 GCTs of various subtypes, and we compared them with 443 other common malignant tumors of epithelial, mesenchymal, and lymphoid origins. Significant differences in gene expression were found among major histological subtypes of GCTs, and between them and other malignancies. We identified 511 genes, belonging to several critical functional groups such as cell cycle progression, cell proliferation, and apoptosis, to be significantly differentially expressed in GCTs compared with other tumor types. Sixty-five genes were sufficient for the construction of a GCT class predictor of high predictive accuracy (100% training set, 96% test set), which might be useful in the diagnosis of tumors of unknown primary origin. Previously described diagnostic and prognostic markers were found to be expressed by the appropriate GCT subtype (AFP, POU5F1, POV1, CCND2, and KIT). Several additional differentially expressed genes were identified in teratomas (EGR1 and MMP7), yolk sac tumors (PTPN13 and FN1), and seminomas (NR6A1, DPPA4, and IRX1). Dynamic computation of interaction networks and mapping to existing pathways knowledge databases revealed a potential role of EGR1 in p21-induced cell cycle arrest and intrinsic chemotherapy resistance of mature teratomas. PMID:16306258
Full Text Available Abstract Background To discover prostate cancer biomarkers, we profiled gene expression in benign and malignant cells laser capture microdissected (LCM from prostate tissues and metastatic prostatic adenocarcinomas. Here we present methods developed, optimized, and validated to obtain high quality gene expression data. Results RNase inhibitor was included in solutions used to stain frozen tissue sections for LCM, which improved RNA quality significantly. Quantitative PCR assays, requiring minimal amounts of LCM RNA, were developed to determine RNA quality and concentration. SuperScript II™ reverse transcriptase was replaced with SuperScript III™, and SpeedVac concentration was eliminated to optimize linear amplification. The GeneChip® IVT labeling kit was used rather than the Enzo BioArray™ HighYield™ RNA transcript labeling kit since side-by-side comparisons indicated high-end signal saturation with the latter. We obtained 72 μg of labeled complementary RNA on average after linear amplification of about 2 ng of total RNA. Conclusion Unsupervised clustering placed 5/5 normal and 2/2 benign prostatic hyperplasia cases in one group, 5/7 Gleason pattern 3 cases in another group, and the remaining 2/7 pattern 3 cases in a third group with 8/8 Gleason pattern 5 cases and 3/3 metastatic prostatic adenocarcinomas. Differential expression of alpha-methylacyl coenzyme A racemase (AMACR and hepsin was confirmed using quantitative PCR.
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
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.
Full Text Available This multicenter cohort study assessed the impact of molecular profiling (MP on advanced pancreaticobiliary cancer (PBC. The study included 30 patients treated with MP-guided therapy after failing ≥1 therapy for advanced PBC. Treatment was considered as having benefit for the patient if the ratio between the longest progression-free survival (PFS on MP-guided therapy and the PFS on the last therapy before MP was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit. Overall, ≥1 actionable (i.e., predictive of response to specific therapies biomarker was identified/patient. Immunohistochemistry (the most commonly used method for guiding treatment decisions identified 1–6 (median: 4 actionable biomarkers per patient. After MP, patients received 1–4 (median: 1 regimens/patient (most commonly, FOLFIRI/XELIRI. In a decision-impact analysis, of the 27 patients for whom treatment decisions before MP were available, 74.1% experienced a treatment decision change in the first line after MP. Twenty-four patients were evaluable for clinical outcome analysis; in 37.5%, the PFS ratio was ≥1.3. In one-sided exact binomial test versus the null hypothesis, P = 0.0015; therefore, the null hypothesis was rejected. In conclusion, our analysis demonstrated the feasibility, clinical decision impact, and potential clinical benefits of MP-guided therapy in advanced PBC.
Jung, Myung Hwan; Park, Jeong Chan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)
Cancer stem cells (CSCs) possess characteristics associated with normal stem cells. The mechanisms regulating CSC radio-resistance, including to proton beam, remain unclear. They showed that a subset of cells expressing CD44 with weak or no CD24 expression could establish new tumors in xenograft mice. Recently, BCSC-targeting therapies have been evaluated by numerous groups. Strategies include targeting BCSC self-renewal, indirectly targeting the microenvironment, and directly killing BCSCs by chemical agents that induce differentiation, immunotherapy, and oncolytic viruses. However, the mechanisms regulating CSC radio-resistance, particularly proton beam resistance, remain unclear. The identification of CSC-related gene expression patterns would make up offer data for better understanding CSCs properties. In this study we investigated the gene expression profile of BCSCs isolation from MCF-7 cell line. Reducing BCSC resistance to pulsed proton beams is essential to improve therapeutic efficacy and decrease the 5-year recurrence rate. In this respect, the information of the level of gene expression patterns in BCSCs is attractive for understanding molecular mechanisms of radio-resistance of BCSCs.
Endo, Takumi; Uzawa, Katsuhiro; Suzuki, Hiroyoshi; Tanzawa, Hideki; Ichikawa, Tomohiko
The molecular mechanism playing a role in the development of benign prostate hypertrophy (BPH) and prostate cancer (PC) is not well defined. We performed microarray analysis to assess the gene expression change in BPH and PC, and performed network analysis. Normal prostate, BPH and PC tissues were obtained from patients who underwent an operation at Chiba University Hospital. Using Affymetrix Human Genome U133 Plus2.0 Array, we identified genes differentially expressed. The identified genes were analyzed using the Ingenuity Pathway Analysis (IPA) to investigate the functional network and gene ontology. The microarray analysis identified 402 genes in BPH and 141 genes in PC, which were up- or down-regulated at least 5.0-fold change in PC at all dose points. Analysis using IPA software revealed eight networks in BPH and five networks in PC. We narrowed these down to the top five genes, which were up- or down-regulated on the networks in their characteristic manner. From this new perspective, comparing BPH and PC in microarray studies, our data showing gene expression profiles provide candidate genes for better understanding of disease and new therapeutic targets.
Agar, John W; Perkins, Anthony; Heaf, James G
We describe the infrastructure that is necessary for hemodialysis in the home focusing on physical requirements, the organization of plumbing and water, and the key features that should guide the selection of machines that are suitable for home use....
Full Text Available High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS is an emerging application for the comprehensive and detailed analysis of the spatial distribution of ionized molecules in situ on tissue slides. HR-MALDI-IMS in negative mode in a mass range of m/z 500-1000 was performed on optimal cutting temperature (OCT compound-embedded human prostate tissue samples obtained from patients with prostate cancer at the time of radical prostatectomy. HR-MALDI-IMS analysis of the 14 samples in the discovery set identified 26 molecules as highly expressed in the prostate. Tandem mass spectrometry (MS/MS showed that these molecules included 14 phosphatidylinositols (PIs, 3 phosphatidylethanolamines (PEs and 3 phosphatidic acids (PAs. Among the PIs, the expression of PI(18:0/18:1, PI(18:0/20:3 and PI(18:0/20:2 were significantly higher in cancer tissue than in benign epithelium. A biomarker algorithm for prostate cancer was formulated by analyzing the expression profiles of PIs in cancer tissue and benign epithelium of the discovery set using orthogonal partial least squares discriminant analysis (OPLS-DA. The sensitivity and specificity of this algorithm for prostate cancer diagnosis in the 24 validation set samples were 87.5 and 91.7%, respectively. In conclusion, HR-MALDI-IMS identified several PIs as being more highly expressed in prostate cancer than benign prostate epithelium. These differences in PI expression profiles may serve as a novel diagnostic tool for prostate cancer.
Larsen, Martin J; Thomassen, Mads; Tan, Qihua
BACKGROUND: In more than 70% of families with a strong history of breast and ovarian cancers, pathogenic mutation in BRCA1 or BRCA2 cannot be identified, even though hereditary factors are expected to be involved. It has been proposed that tumors with similar molecular phenotypes also share similar...... underlying pathophysiological mechanisms. In the current study, the aim was to investigate if global RNA profiling can be used to identify functional subgroups within breast tumors from families tested negative for BRCA1/2 germline mutations and how these subgroupings relate to different breast cancer...... patients within the same family. METHODS: In the current study we analyzed a collection of 70 frozen breast tumor biopsies from a total of 58 families by global RNA profiling and promoter methylation analysis. RESULTS: We show that distinct functional subgroupings, similar to the intrinsic molecular breast...
Vogel Lotte K
Full Text Available Abstract Background Several studies have shown that NDRG2 mRNA is down-regulated or undetectable in various human cancers and cancer cell-lines. Although the function of NDRG2 is currently unknown, high NDRG2 expression correlates with improved prognosis in high-grade gliomas, gastric cancer and hepatocellular carcinomas. Furthermore, in vitro studies have revealed that over-expression of NDRG2 in cell-lines causes a significant reduction in their growth. The aim of this study was to examine levels of NDRG2 mRNA in several human cancers, with focus on breast cancer, by examining affected and normal tissue. Methods By labelling a human Cancer Profiling Array with a radioactive probe against NDRG2, we evaluated the level of NDRG2 mRNA in 154 paired normal and tumor samples encompassing 19 different human cancers. Furthermore, we used quantitative real-time RT-PCR to quantify the levels of NDRG2 and MYC mRNA in thyroid gland cancer and breast cancer, using a distinct set of normal and tumor samples. Results From the Cancer Profiling Array, we saw that the level of NDRG2 mRNA was reduced by at least 2-fold in almost a third of the tumor samples, compared to the normal counterpart, and we observed a marked decreased level in colon, cervix, thyroid gland and testis. However, a Benjamini-Hochberg correction showed that none of the tissues showed a significant reduction in NDRG2 mRNA expression in tumor tissue compared to normal tissue. Using quantitative RT-PCR, we observed a significant reduction in the level of NDRG2 mRNA in a distinct set of tumor samples from both thyroid gland cancer (p = 0.02 and breast cancer (p = 0.004, compared with normal tissue. MYC mRNA was not significantly altered in breast cancer or in thyroid gland cancer, compared with normal tissue. In thyroid gland, no correlation was found between MYC and NDRG2 mRNA levels, but in breast tissue we found a weakly significant correlation with a positive r-value in both normal and
Wendy W Hwang-Verslues
Full Text Available Heterogeneity of cancer stem/progenitor cells that give rise to different forms of cancer has been well demonstrated for leukemia. However, this fundamental concept has yet to be established for solid tumors including breast cancer. In this communication, we analyzed solid tumor cancer stem cell markers in human breast cancer cell lines and primary specimens using flow cytometry. The stem/progenitor cell properties of different marker expressing-cell populations were further assessed by in vitro soft agar colony formation assay and the ability to form tumors in NOD/SCID mice. We found that the expression of stem cell markers varied greatly among breast cancer cell lines. In MDA-MB-231 cells, PROCR and ESA, instead of the widely used breast cancer stem cell markers CD44(+/CD24(-/low and ALDH, could be used to highly enrich cancer stem/progenitor cell populations which exhibited the ability to self renew and divide asymmetrically. Furthermore, the PROCR(+/ESA(+ cells expressed epithelial-mesenchymal transition markers. PROCR could also be used to enrich cells with colony forming ability from MB-361 cells. Moreover, consistent with the marker profiling using cell lines, the expression of stem cell markers differed greatly among primary tumors. There was an association between metastasis status and a high prevalence of certain markers including CD44(+/CD24(-/low, ESA(+, CD133(+, CXCR4(+ and PROCR(+ in primary tumor cells. Taken together, these results suggest that similar to leukemia, several stem/progenitor cell-like subpopulations can exist in breast cancer.
Full Text Available 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
Winkler, Volker; Ott, Jördis J; Holleczek, Bernd; Stegmaier, Christa; Becher, Heiko
This study compares cancer mortality and incidence of ethnic German migrants from the Former Soviet Union (FSU) in Germany. Data were obtained from two migrant cohorts residing in the federal state of North Rhine-Westphalia (NRW) (n = 34,393) and Saarland (n = 18,619). Vital status of the NRW cohort was ascertained through local population registries. Causes of death were obtained from the NRW statistical office or from local health offices. Cancer incidence of the Saarland cohort was derived from the Saarland cancer registry using record linkage. From 1990 to 2005, we observed 708 cancer deaths and 586 incident cancer cases. In males, both cancer incidence and cancer mortality were similar to the German population. Female cancer incidence and mortality were lower, the latter significantly. Site-specific standardized mortality and incidence ratios showed great variation in comparison to Germans and were remarkably similar to each other for most sites. Lung cancer was elevated among males, but lower among females. Stomach cancer was higher contrasting with lower ratios for prostate cancer, male colorectal cancer, and female breast cancer. Results confirm that FSU-migrants suffer from cancers, which may be prevented by prevention programs. Furthermore, we cannot conclude a different health-seeking behavior compared to Germans.
Full Text Available Abstract Background The discovery of the importance of angiogenesis in tumor growth has emphasized the need to find specific vascular targets for tumor-targeted therapies. Previously, using phage display technology, we identified the peptide GX1 as having the ability to target the gastric cancer vasculature. The present study investigated the bioactivities of GX1, as well as its potential ability to cooperate with recombinant mutant human tumor necrosis factor alpha (rmhTNFα, in gastric cancer therapy. Results Tetrazolium salt (MTT assay showed that GX1 could inhibit cell proliferation of both human umbilical vein endothelial cells (HUVEC (44% and HUVEC with tumor endothelium characteristics, generated by culturing in tumor-conditioned medium (co-HUVEC (62%. Flow-cytometry (FCM and western blot assays showed that GX1 increased the rate of apoptosis from 11% to 31% (p in vivo, with the microvessel count decreasing from 21 to 11 (p In vitro MTT and FCM assays showed that, compared to rmhTNFα alone, GX1-rmhTNFα was more effective at suppressing co-HUVEC proliferation (45% vs. 61%, p p 3 vs. 134 mm3, p p Conclusion GX1 had both homing activity and the ability to inhibit vascular endothelial cell proliferation in vitro and neovascularization in vivo. Furthermore, when GX1 was conjugated to rmhTNFα, the fusion protein was selectively delivered to targeted tumor sites, significantly improving the anti-tumor activity of rmhTNFα and decreasing systemic toxicity. These results demonstrate the potential of GX1 as a homing peptide in vascular targeted therapy for gastric cancer.
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
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.
Bhat, Sujatha; Patil, Ajeetkumar; Rai, Lavanya; Kartha, V B; Chidangil, Santhosh
A highly objective method, High Performance Liquid Chromatography with Laser Induced Fluorescence (HPLC-LIF) technique was used to study the protein profiles of normal and cervical cancer tissue homogenates. A total of 44 samples including normal cervical biopsy samples from the hysterectomy patients and the patients suffering from different stages of the cervical cancer were recorded by HPLC-LIF and analysed by Principle Component Analysis (PCA) to get statistical information on different tissue components. Discrimination of different stages of the samples was carried out by considering three parameters--scores of factor, spectral residual, and Mahalanobis Distance. Diagnostic accuracy of the method was evaluated using Receiver Operating Characteristic (ROC) analysis, and Youden's index (J) plots. The PCA results showed high sensitivity and specificity (~100) for cervical cancer diagnosis. ROC and Youden's index curves for both normal and malignant standard sets show good diagnostic accuracy with high AUC values. The statistical analysis has shown that the differences in protein profiles can be used to diagnose biochemical changes in the tissue, and thus can be readily applied for the detection of cervical cancer, even in situations where a histopathology examination is not easy because of nonavailability of experienced pathologists.
Full Text Available A highly objective method, High Performance Liquid Chromatography with Laser Induced Fluorescence (HPLC-LIF technique was used to study the protein profiles of normal and cervical cancer tissue homogenates. A total of 44 samples including normal cervical biopsy samples from the hysterectomy patients and the patients suffering from different stages of the cervical cancer were recorded by HPLC-LIF and analysed by Principle Component Analysis (PCA to get statistical information on different tissue components. Discrimination of different stages of the samples was carried out by considering three parameters—scores of factor, spectral residual, and Mahalanobis Distance. Diagnostic accuracy of the method was evaluated using Receiver Operating Characteristic (ROC analysis, and Youden's index (J plots. The PCA results showed high sensitivity and specificity (∼100 for cervical cancer diagnosis. ROC and Youden's index curves for both normal and malignant standard sets show good diagnostic accuracy with high AUC values. The statistical analysis has shown that the differences in protein profiles can be used to diagnose biochemical changes in the tissue, and thus can be readily applied for the detection of cervical cancer, even in situations where a histopathology examination is not easy because of nonavailability of experienced pathologists.
Popim, Regina Célia; Corrente, José Eduardo; Marino, Jaqueline Aparecida Geromel; de Souza, Carolina Arantes
The aim of this paper was to establish the demographic profile of an at-risk group for skin cancer and to assess the preventive measures taken by the studied individuals and by the employer. The methods chosen was a quantitative study with a sample of 33 mail carriers from the Empresa Brasileira de Correios e Telégrafos in Botucatu, Brazil. Information regarding the demographic profile, how long the individual had been working for the company, hours of sun exposure, history of sunburns, family cancer history and skin cancer prevention strategies used by the company was collected by means of a questionnaire. The data were analyzed using Fisher's Exact Test at a 5% probability. The predominant age groups were 26-30 and 31-35 years corresponding to 42,42%. The predominant skin color was white (93,94%) and 81,82% of the studied individuals were working in the company for over five years. 63,63% of the interviewees use sunscreen habitually; those who do not explain this with a lack of habit (in 75% of the cases). As refers to supply of protective equipment by the company, 100% of the subjects answered positively. These findings allow characterizing the studied population as a skin cancer risk group. Prophylactic measures in form of educational actions for awareness building should be adopted and stimulated.
Full Text Available Abstract Background Postmenopausal hormone-replacement therapy (HRT increases breast-cancer risk. The influence of HRT on the biology of the primary tumor, however, is not well understood. Methods We obtained breast-cancer gene expression profiles using Affymetrix human genome U133A arrays. We examined the relationship between HRT-regulated gene profiles, tumor characteristics, and recurrence-free survival in 72 postmenopausal women. Results HRT use in patients with estrogen receptor (ER protein positive tumors (n = 72 was associated with an altered regulation of 276 genes. Expression profiles based on these genes clustered ER-positive tumors into two molecular subclasses, one of which was associated with HRT use and had significantly better recurrence free survival despite lower ER levels. A comparison with external data suggested that gene regulation in tumors associated with HRT was negatively correlated with gene regulation induced by short-term estrogen exposure, but positively correlated with the effect of tamoxifen. Conclusion Our findings suggest that post-menopausal HRT use is associated with a distinct gene expression profile related to better recurrence-free survival and lower ER protein levels. Tentatively, HRT-associated gene expression in tumors resembles the effect of tamoxifen exposure on MCF-7 cells.
Sujatha; Rai, Lavanya; Kumar, Pratap; Mahato, Krishna K; Kartha, Vasudevan B; Santhosh, Chidangil
High performance liquid chromatography with high sensitivity laser-induced fluorescence detection is used to study the protein profiles of serum samples from healthy volunteers and cervical cancer subjects. The protein profiles are subjected to principal component analysis (PCA). PCA shows that the large number of chromatograms of a given class of serum samples--say normal/malignant--can be expressed in terms of a small number of factors (principal components). Three parameters--scores of the factors, squared residuals, and Mahalanobis distance--are derived from PCA. The parameters are observed to have a narrow range for protein profiles of standard calibration sets formed from groups of clinically confirmed normal/malignant classes. Limit tests using match/no match of the parameters of any test sample with parameters derived for the standard calibration sets give very good discrimination between malignant and normal samples with high sensitivity (approximately 100%) aand specificity (approximately 94%).
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
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
Rod, Naja Hulvej; Hansen, Ase Marie; Nielsen, Jens;
Obesity, alcohol consumption, physical inactivity and postmenopausal hormone use are known modifiable risk factors for breast cancer. We aim to measure incidence rates of breast cancer for women with favorable levels on all 4 risk factors (BMI...
Ferreira, Flávia Regina; Ogawa, Marilia Marufuji; Nascimento, Luiz Fernando Costa; Tomimori, Jane
BACKGROUND: Nonmelanoma skin cancer is the most common form of cancer in humans and also the malignant disease that is increasingly common among kidney transplant recipients. OBJECTIVE: To determine the epidemiological characteristics of renal transplant recipients with nonmelanoma skin cancer seen at a referral transplantation center. METHODS: Cross-sectional descriptive study with renal transplant recipients presenting nonmelanoma skin cancer, treated at a transplantation referral cente...
Full Text Available Background: A large number of gene expression profiling (GEP studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis. Materials and Methods: We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9% had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO categories or Kyoto Encyclopedia of Genes and Genomes (KEGG pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration. Results: Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities. Conclusions: We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.
Chougule, Anuradha; Kane, Subhadha; Kumar, Rajiv; Mahajan, Abhishek; Janu, Amit
Objectives To evaluate the performance and treatment profile of advanced EML4—ALK positive Non-small cell lung cancer (NSCLC) patients in a developing country with potentially restricted access to Crizotinib. Materials and Methods A retrospective analysis of advanced ALK positive NSCLC patients who were treated from June 2012 to September 2015 was conducted. The primary goal was to evaluate outcomes of advanced ALK positive NSCLC in our practice and examine the logistic constraints in procuring Crizotinib. Results 94 patients were available for analysis. 21 (22.3%) patients were started on Crizotinib upfront, 60 (63.8%) on chemotherapy, 10 (10.6%) on Tyrosine kinase inhibitors (in view of poor PS) and 3 (3.2%) patients were offered best supportive care. Reasons for not starting Crizotinib upfront included symptomatic patients needing early initiation of therapy (23.3%), ALK not tested upfront (23.3%) and financial constraints (21.9%). 69 patients (73.4%) received Crizotinib at some stage during treatment. Dose interruptions (> 1 week) with Crizotinib were seen in 20 patients (29%), with drug toxicity being the commonest reason (85%). Median Progression free survival (PFS) on first line therapy for the entire cohort was 10 months, with a significant difference between patients receiving Crizotinib and those who did not ever receive Crizotinib (10 months vs. 2 months, p = 0.028). Median Overall Survival (OS) was not reached for the entire cohort, with 1 year survival being 81.2%. Patients with an ECOG Performance Status (PS) of >2 had a significantly reduced PFS compared to patients with PS schemes. Conclusion A majority of our ALK positive NSCLC patients were exposed to Crizotinib through the help of various support mechanisms and these patients had similar outcomes to that reported from previously published literature. PMID:27637025
Carcel-Trullols, Jaime; Stanley, Joseph S; Saha, Rinku; Shaaf, Saeid; Bendre, Manali S; Monzavi-Karbassi, Behjatolah; Suva, Larry J; Kieber-Emmons, Thomas
The mechanisms that guide organ-specific metastases are not fully established. The aberrant expression of carbohydrates may play a fundamental role in defining the molecular mechanisms for metastases to distant organs and facilitate positive interactions within the target organ. The purpose of the present study was to determine the glycomic profile of a variant of the MDA-MB-231 breast cancer cell line that colonizes the bone and to ascribe mechanistic functions mediated by carbohydrates that might correlate with clinical bone metastases. The carbohydrate expression profiles of osteolytic MDA-MET breast cancer cells and non-osteolytic parental MDA-MB-231 cells were determined. MDA-MET cells were derived from MDA-MB-231 cells by in vivo selection of metastatic bone lesions following intracardiac inoculation. The two related breast cancer cell lines expressed distinct carbohydrate profiles; MDA-MET cells displayed an increased expression of alpha (2,6) linked sialic acid, N-beta1-6 GlcNAc, and sialylated Lewis-A antigen, and decreased expression of Galbeta1,3GalNAc as detected using a combination of lectins and anti-carbohydrate antibodies. Microarray analysis demonstrated an increased expression of glycosyltransferase genes, correlative for the distinct glycomic phenotype. The altered glycomic phenotypes of MDA-MET cells include effects on the differential binding to bone marrow endothelial cells, enhanced ECM binding and an increase in invasive potential. These data suggest that the glycomic phenotype of MDA-MET cells is associated with a select set of accumulated functions that collectively impact on the bone metastases and bone colonization capacity of breast cancer cells.
Li R.; Visser, H.M.
Chemotherapy and hormonal therapy as adjuvant systemic therapies to inhibit breast cancer recurrence are not necessary for each patient. In Veer's paper "Gene expression profiling predicts clinical outcome of breast cancer" (Nature 2002, PMID: 11823860), they introduced a method based on DNA microa
Full Text Available Cadmium is a metalloestrogen known to activate the estrogen receptor and promote breast cancer cell growth. Previous studies have implicated cadmium in the development of more malignant tumors; however the molecular mechanisms behind this cadmium-induced malignancy remain elusive. Using clonal cell lines derived from exposing breast cancer cells to cadmium for over 6 months (MCF-7-Cd4, -Cd6, -Cd7, -Cd8 and -Cd12, this study aims to identify gene expression signatures associated with chronic cadmium exposure. Our results demonstrate that prolonged cadmium exposure does not merely result in the deregulation of genes but actually leads to a distinctive expression profile. The genes deregulated in cadmium-exposed cells are involved in multiple biological processes (i.e. cell growth, apoptosis, etc. and molecular functions (i.e. cadmium/metal ion binding, transcription factor activity, etc.. Hierarchical clustering demonstrates that the five clonal cadmium cell lines share a common gene expression signature of breast cancer associated genes, clearly differentiating control cells from cadmium exposed cells. The results presented in this study offer insights into the cellular and molecular impacts of cadmium on breast cancer and emphasize the importance of studying chronic cadmium exposure as one possible mechanism of promoting breast cancer progression.
Lubovac-Pilav, Zelmina; Borràs, Daniel M; Ponce, Esmeralda; Louie, Maggie C
Cadmium is a metalloestrogen known to activate the estrogen receptor and promote breast cancer cell growth. Previous studies have implicated cadmium in the development of more malignant tumors; however the molecular mechanisms behind this cadmium-induced malignancy remain elusive. Using clonal cell lines derived from exposing breast cancer cells to cadmium for over 6 months (MCF-7-Cd4, -Cd6, -Cd7, -Cd8 and -Cd12), this study aims to identify gene expression signatures associated with chronic cadmium exposure. Our results demonstrate that prolonged cadmium exposure does not merely result in the deregulation of genes but actually leads to a distinctive expression profile. The genes deregulated in cadmium-exposed cells are involved in multiple biological processes (i.e. cell growth, apoptosis, etc.) and molecular functions (i.e. cadmium/metal ion binding, transcription factor activity, etc.). Hierarchical clustering demonstrates that the five clonal cadmium cell lines share a common gene expression signature of breast cancer associated genes, clearly differentiating control cells from cadmium exposed cells. The results presented in this study offer insights into the cellular and molecular impacts of cadmium on breast cancer and emphasize the importance of studying chronic cadmium exposure as one possible mechanism of promoting breast cancer progression.
Catelan, Dolores; Buzzoni, Carlotta; Coviello, Enzo; Crocetti, Emanuele; Pasetto, Roberto; Pirastu, Roberta; Biggeri, Annibale
Epidemiological surveillance on high risk environmental areas or areas covered by cancer registration yields long inventories of relative risks. Summaries of the results' tables must be produced to identify priorities and tailor public health actions. The aim is, therefore, to draw conclusions from each area's disease profile, or from the area signature of each disease.With this inmind, we used data on cancer incidence from 17 Cancer Registries that participated in the ISS-AIRTUM (National Institute of Health-Italian Network of Cancer Registries) study, and we produced conditional and marginal rankings of areas/diseases using a multivariate hierarchical Bayesian model. In this context, it is important to obtain an uncertainty evaluation by calculating the credibility intervals of ranks. The areas marginal ranking shows a large overlapping of credibility intervals, such that it is not possible to speak of a limited number of ISS-AIRTUM areas as being particularly affected. Every ISS-AIRTUMarea, therefore,must be considered individually and ordering themby ranking of cancer incidence wouldn't be appropriate. Instead,marginal ranking of diseases highlights the impact of asbestos exposure in all the analyzed areas.
Full Text Available Background: After harvesting the fibula flap, pain, sensory disturbance, weakness of donor leg, reduced walking endurance, ankle instability, and lower walking speed had been reported. The aim of this study was to quantitatively assess functional outcome of regular home-based exercise on donor ankle strength, endurance, and walking ability after free fibula flap for mandibular reconstruction. Methods: Fourteen patients were recruited. Objective isokinetic testing and a 6-min walk test (6MWT were used to evaluate ankle strength/endurance and walking ability, respectively. Results: There was a significant increase in the peak torque of ankle dorsiflexion/foot inversion of the healthy leg and ankle dorsiflexion/foot eversion of the donor leg after exercise (p < 0.05. After home-based exercise, there was reduced asymmetry in the peak torques of ankle dorsiflexion and foot eversion and the total work of foot eversion between the donor and healthy legs. In 6MWT, no significant difference was found between the walking distances before and after exercise. Conclusion: Regular home-based exercise could improve the strength of ankle dorsiflexion and foot eversion of the donor leg, and get more symmetric ankle motor function between the donor and healthy legs.
Full Text Available BACKGROUND: The problem of prostate cancer progression to androgen independence has been extensively studied. Several studies systematically analyzed gene expression profiles in the context of biological networks and pathways, uncovering novel aspects of prostate cancer. Despite significant research efforts, the mechanisms underlying tumor progression are poorly understood. We applied a novel approach to reconstruct system-wide molecular events following stimulation of LNCaP prostate cancer cells with synthetic androgen and to identify potential mechanisms of androgen-independent progression of prostate cancer. METHODOLOGY/PRINCIPAL FINDINGS: We have performed concurrent measurements of gene expression and protein levels following the treatment using microarrays and iTRAQ proteomics. Sets of up-regulated genes and proteins were analyzed using our novel concept of "topological significance". This method combines high-throughput molecular data with the global network of protein interactions to identify nodes which occupy significant network positions with respect to differentially expressed genes or proteins. Our analysis identified the network of growth factor regulation of cell cycle as the main response module for androgen treatment in LNCap cells. We show that the majority of signaling nodes in this network occupy significant positions with respect to the observed gene expression and proteomic profiles elicited by androgen stimulus. Our results further indicate that growth factor signaling probably represents a "second phase" response, not directly dependent on the initial androgen stimulus. CONCLUSIONS/SIGNIFICANCE: We conclude that in prostate cancer cells the proliferative signals are likely to be transmitted from multiple growth factor receptors by a multitude of signaling pathways converging on several key regulators of cell proliferation such as c-Myc, Cyclin D and CREB1. Moreover, these pathways are not isolated but constitute an
Full Text Available Background: Patients who undergo emergency colorectal cancer surgery has poor outcome compared to elective surgery, both in terms of morbidity and mortality. Approximately 15 to 30% of colorectal cancers present as an emergency, most often as obstruction or perforation. Objective: To compare surgical outcome and clinical profiles of emergency and elective cases for colorectal cancer. Methods: Retrospective analysis of 34 cases who underwent surgery for colorectal cancer between December 2011 to January 2013was carried out and their surgical outcomes, clinical presentation, demographic profile were analyzed. Results: The total numbers of patients included in this study were 34. Out of which 52.94 %( n=18 were emergency cases and 47.05 %( n=16 were elective. Male female ratio was 3:1 in emergency cases and 2.6:1 in elective cases. Per rectal bleeding (56% and altered bowel habit (31.25% was predominant clinical presentation in elective cases whereas intestinal obstruction (55.55% and peritonitis (22.22% were predominant clinical presentation in emergency cases. In emergency cases most of the tumors were located in left side (77.77% and in elective cases rectum was common site (37.5%. Left hemicolectomy was the commonest surgery performed (72.22% in emergency set up. In elective cases, right hemicolectomy, left hemicolectomy, APR and LAR was done in 31.25%, 31.25%, 25% and 25% cases respectively. In the emergency group 11.11% (n=2 developed enterocutaneous fistula and early mortality within 30 days was observed in 5% (n=1 of emergency cases only. Conclusion: In emergency conditions, colorectal cancer presented with intestinal obstruction where as elective cases presented with per rectal bleeding and altered bowel habits. Compared with the elective patients, the emergency patients had higher rate of morbidity and mortality. Because of higher incidence of colorectal cancer in our institution, in all emergency cases who presents with features of
Moussawi, Ahmad H; Yassine, May; Dey, Subhojit; Soliman, Amr S
Prostate cancer is the most common cancer among men in the United States with striking differences in incidence and mortality among ethnic groups. Michigan has one of the largest concentrations of Arab Americans (AAs) in the U.S. and little is known about this ethnic minority with respect to prostate cancer. This study investigated differences in clinical profile, quality of care, and recurrence among prostate cancer survivors comparing AAs and Caucasian Americans (CAs). Participants in this study included 2499 prostate cancer survivors from the Michigan Cancer Registry from 1985 to 2004. Participants completed surveys regarding health-seeking behavior, post-treatment symptoms, quality of care and recurrence. Ethnicity was self-reported and AAs and CAs were compared with respect to clinical profile, quality of care, and recurrence. There were 52 AAs and 1886 CAs patients with AAs being younger ([Formula: see text] age 68.3 ± SD 21.4 years, [Formula: see text] age 72.3 ± SD 14.1 years, for AAs and CAs, respectively) (P = 0.05). AAs had lower socioeconomic standard than CAs (34 vs. 10.6 %, <$20,000 yearly income/year; for AAs vs. CAs, respectively) (P < 0.0001). AAs reported poorer health than AAs (7.7 vs. 3.0 % for AAs vs. CAs, respectively) (P < 0.0001). AAs were more likely to visit specialists for prostate follow-up (44.5 vs. 19.7 % visited a specialist, for AAs vs. CAs respectively) (P < 0.0001) and received supplementary healthcare workers (13 % of AAs vs. 3.1 % CAs) (P = 0.032). In addition, AAs reported higher occurrence of urinary incontinence compared to CAs (67.4 vs. 60.4 %, for AAs vs. CAs, respectively) (P = 0.001). Ethnic background was not a predictor of recurrence [(Odds ratio (OR) = 1.1 (95 % confidence intervals CI = 0.40, 2.9)] (P = 0.873) even after adjusting for age, PSA levels within the last 2 years, metastasis and hormonal therapy. While AAs prostate cancer patients were different from CAs in age, income
Full Text Available Abstract Background Lung cancers are the most common type of human malignancy and are intractable. Lung cancers are generally classified into four histopathological subtypes: adenocarcinoma (AD, squamous cell carcinoma (SQ, large cell carcinoma (LC, and small cell carcinoma (SC. Molecular biological characterization of these subtypes has been performed mainly using DNA microarrays. In this study, we compared the gene expression profiles of these four subtypes using twelve human lung cancer cell lines and the more reliable quantitative real-time PCR (qPCR. Results We selected 100 genes from public DNA microarray data and examined them by DNA microarray analysis in eight test cell lines (A549, ABC-1, EBC-1, LK-2, LU65, LU99, STC 1, RERF-LC-MA and a normal control lung cell line (MRC-9. From this, we extracted 19 candidate genes. We quantified the expression of the 19 genes and a housekeeping gene, GAPDH, with qPCR, using the same eight cell lines plus four additional validation lung cancer cell lines (RERF-LC-MS, LC-1/sq, 86-2, and MS-1-L. Finally, we characterized the four subtypes of lung cancer cell lines using principal component analysis (PCA of gene expression profiling for 12 of the 19 genes (AMY2A, CDH1, FOXG1, IGSF3, ISL1, MALL, PLAU, RAB25, S100P, SLCO4A1, STMN1, and TGM2. The combined PCA and gene pathway analyses suggested that these genes were related to cell adhesion, growth, and invasion. S100P in AD cells and CDH1 in AD and SQ cells were identified as candidate markers of these lung cancer subtypes based on their upregulation and the results of PCA analysis. Immunohistochemistry for S100P and RAB25 was closely correlated to gene expression. Conclusions These results show that the four subtypes, represented by 12 lung cancer cell lines, were well characterized using qPCR and PCA for the 12 genes examined. Certain genes, in particular S100P and CDH1, may be especially important for distinguishing the different subtypes. Our results
Ninety-year-old Ivy Tabberer protested against the closure of her care home at the Houses of Parliament last week. She was joined by fellow residents in the Havering Action Against Home Closures group and three generations of her family. Ms Tabberer is pictured with daughter Doreen Walpole (left), granddaughter Annette (far right) and great granddaughter Shereen (middle). 'If all the homes close,' said Ms Tabberer, 'where are we going to stay?'
... triggering an emergency response or checkup phone call. Healthcare professionals are finding that portable or mobile testing technology (home diagnostics), including x-rays and electrocardiograms (ECGs), ...
Lyng, Maria B; Kodahl, Annette R; Binder, Harald;
is significantly different between women with breast cancer and controls (p-value woman whose 9-miRNA profile predicted a 73% probability of having breast cancer indeed developed the disease within one year despite being categorized as clinically healthy...... developed a 9-miRNA profile using serum and LNA-based qPCR that effectively stratified patients with early stage breast cancer vs. healthy women. To further develop the test into routine clinical practice, we collected serum of women examined by clinical mammography (N = 197) according to standard...
Chen, Qing-yong; Jiao, De-min; Yan, Li; Wu, Yu-quan; Hu, Hui-zhen; Song, Jia; Yan, Jie; Wu, Li-jun; Xu, Li-qun; Shi, Jian-guo
MiRNAs associated with the metastasis of lung cancer remain largely unexplored. In this study, gene and miRNA expression profiling were performed to analyze the global expression of mRNAs and miRNAs in human high- and low-metastatic lung cancer cell strains. By developing an integrated bioinformatics analysis, six miRNAs (miR-424-3p, miR-450b-5p, miR-335-5p, miR-34a-5p, miR-302b-3p and miR-206) showed higher target gene degrees in the miRNA-gene network and might be potential metastasis-related miRNAs. Using the qRT-PCR method, the six miRNAs were further confirmed to show a significant expression difference between human lung cancer and normal tissue samples. Since miR-206 showed lower expression both in lung cancer tissues and cell lines, it was used as an example for further functional verification. The wound healing assay and transwell invasion assay showed that miR-206 mimics significantly inhibited the cell migration and invasion of the high-metastatic lung cancer 95D cell strain. One of its predicted targets in our miRNA-gene network, MET, was also obviously decreased at the protein level when miR-206 was overexpressed. Instead, miR-206 inhibitors increased MET protein expression, cell migration and invasion of the low-metastatic lung cancer 95C cell strain. Meanwhile, the luciferase assay showed that MET was a direct target of miR-206. Furthermore, MET gene silence showed a similar anti-migration and anti-invasion effect with miR-206 mimics in 95D cells and could partially attenuate the migration- and invasion-promoting effect of miR-206 inhibitors in 95C cells, suggesting that miR-206 targets MET in lung cancer metastasis. Finally, we also demonstrated that miR-206 can significantly inhibit lung cancer proliferation and metastasis in mouse models. In conclusion, our study provided a miRNA-gene regulatory network in lung cancer metastasis and further demonstrated the roles of miR-206 and MET in this process, which enhances the understanding of the
Imam, Shahnawaz; Paparodis, Rodis; Sharma, Deepak; Jaume, Juan Carlos
Thyroid cancers are usually surrounded by a significant number of immune-reactive cells. Tumor-associated lymphocytes as well as background lymphocytic thyroiditis are frequently mentioned in pathology reports of patients who have undergone surgery for thyroid cancer. The nature of this lymphocytic reaction is not well understood. The fact that cancer can survive in this adverse microenvironment is indicative of immune regulation. We characterized the lymphocytic infiltration that accompanies thyroid cancer and compared it with that present in thyroid autoimmunity. We found that double-negative (DN) T cells were significantly more abundant in thyroid cancer than in thyroid autoimmunity. Although FOXP3(+) regulatory T cells were also present, DN T cells were the dominant cell type, associated with thyroid cancer. Furthermore, upon stimulation, the DN T cells associated with cancer remained unchanged, while the few (20%). CD25 expression on DN T cells remained unchanged after stimulation, which indicates that the increase in the absolute number of DN T cells in thyroid autoimmunity was at the expense of inactivation of single-positive T cells. We concluded that in the setting of thyroid cancer, DN T cells appear to suppress tumor immunity. In contrast, in thyroid autoimmunity, DN T cells were barely present and only increased at the expense of inactivated, single-positive T cells upon induction. Together, these findings indicate that thyroid cancer-associated DN T cells might regulate proliferation and effector function of T cells and thereby contribute to tumor tolerance and active avoidance of tumor immunity.
Full Text Available 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.
Cornen, Stéphanie; Guille, Arnaud; Adélaïde, José; Addou-Klouche, Lynda; Finetti, Pascal; Saade, Marie-Rose; Manai, Marwa; Carbuccia, Nadine; Bekhouche, Ismahane; Letessier, Anne; Raynaud, Stéphane; Charafe-Jauffret, Emmanuelle; Jacquemier, Jocelyne; Spicuglia, Salvatore; de The, Hugues; Viens, Patrice; Bertucci, François; Birnbaum, Daniel; Chaffanet, Max
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.
Full Text Available Abstract Background Determining the primary site of metastatic cancer with confidence can be challenging. Pathologists commonly use a battery of immunohistochemical (IHC stains to determine the primary site. Gene expression profiling (GEP has found increasing use, particularly in the most difficult cases. In this pilot study, a direct comparison between GEP and IHC-guided methods was performed. Methods Ten archived formalin-fixed paraffin embedded metastatic tumor samples for which the primary site had been clinically determined were selected. Five pathologists who were blinded to the diagnosis were asked to determine the primary site using IHC and other stains selected from a panel of 84 stains. Each pathologist was provided patient sex, biopsy site and gross sample description only. Slides were digitized using ScanScope®XT at 0.25 μm/pixel. Each evaluating pathologist was allowed to provide a diagnosis in three stages: initial (after reviewing the H&E image, intermediate (after reviewing images from the first batch of stains and final diagnosis (after the second batch of stains if requested. GEP was performed using the only FDA-cleared test for this intended use, the Pathwork Tissue of Origin Test. No sample information was provided for GEP testing except for patient sex. Results were reported as the tumor tissue type with the highest similarity score. Results In this feasibility study, GEP determined the correct primary site in 9 of the 10 cases (90%, compared to the IHC-guided method which determined the correct primary site for 32 of 50 case evaluations (average 64%, range 50% to 80%. The five pathologists directing the IHC-guided method ordered an average of 8.8 stains per case (range 1 to 18. GEP required an average of 3 slides per case (range 1 to 4. Conclusions Results of the pilot study suggest that GEP provides correct primary site identification in a higher percentage of metastatic cases than IHC-guided methods, and uses less
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Lebovitz, Chandra B; Robertson, A Gordon; Goya, Rodrigo; Jones, Steven J; Morin, Ryan D; Marra, Marco A; Gorski, Sharon M
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.
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
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
Van Hemelrijck, Mieke; Wigertz, Annette; Sandin, Fredrik; Garmo, Hans; Hellström, Karin; Fransson, Per; Widmark, Anders; Lambe, Mats; Adolfsson, Jan; Varenhorst, Eberhard; Johansson, Jan-Erik; Stattin, Pär
In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case-control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.
Winther, Ida Wentzel
, but to revitalize it to prevent it from turning into a pell-mell or a zombie (Beck 1999). This is important because we are moving away from the hegemonic idea of one home to the tactics of feeling at home, even in more mobile ways. The study is cross-disciplinary, drawing on cultural phenomenology, the history...
George, G Victo Sudha; 10.5121/ijcses.2011.2302
The DNA microarray technology has modernized the approach of biology research in such a way that scientists can now measure the expression levels of thousands of genes simultaneously in a single experiment. Gene expression profiles, which represent the state of a cell at a molecular level, have great potential as a medical diagnosis tool. But compared to the number of genes involved, available training data sets generally have a fairly small sample size for classification. These training data limitations constitute a challenge to certain classification methodologies. Feature selection techniques can be used to extract the marker genes which influence the classification accuracy effectively by eliminating the un wanted noisy and redundant genes This paper presents a review of feature selection techniques that have been employed in micro array data based cancer classification and also the predominant role of SVM for cancer classification.
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.
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.
(P<0.05. Conclusion. The technique of capillary electrophoresis mass spectrometry based on MRB could reveal the significant metabolic alterations during progression of colorectal cancer, and the method is feasible and may be useful for the early diagnosis of colorectal cancer.
serve as potential targets for chemoprevention. Table 1. Clinico -pathological features of NSCLCs cases examined in the Field Cancerization Study... Clinico -pathological features of NSCLCs cases examined in the Field Cancerization Study Covariate Levels N (%) Covariate Levels N (%) Gender Female 11...Anderson institutional review board (IRB)-approved protocol. A summary of the clinicopathological characteristics of the studied patient cases is
Full Text Available E Clair McClung, Robert M WenhamDepartment of Gynecologic Oncology, H. Lee Moffitt Cancer Center, Tampa, FL, USAAbstract: Patients with platinum-resistant ovarian cancer have progression of disease within 6 months of completing platinum-based chemotherapy. While several chemotherapeutic options exist for the treatment of platinum-resistant ovarian cancer, the overall response to any of these therapies is ~10%, with a median progression-free survival of 3–4 months and a median overall survival of 9–12 months. Bevacizumab (Avastin, a humanized, monoclonal antivascular endothelial growth factor antibody, has demonstrated antitumor activity in the platinum-resistant setting and was recently approved by US Food and Drug Administration for combination therapy with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. This review summarizes key clinical trials investigating bevacizumab for recurrent, platinum-resistant ovarian cancer and provides an overview of efficacy, safety, and quality of life data relevant in this setting. While bevacizumab is currently the most studied and clinically available antiangiogenic therapy, we summarize recent studies highlighting novel alternatives, including vascular endothelial growth factor-trap, tyrosine kinase inhibitors, and angiopoietin inhibitor trebananib, and discuss their application for the treatment of platinum-resistant ovarian cancer.Keywords: bevacizumab, angiogenesis, ovarian cancer, platinum-resistant ovarian cancer, recurrent ovarian cancer
Full Text Available 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.
Mavaddat, Nasim; Pharoah, Paul D P; Michailidou, Kyriaki
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. M...
N. Mavaddat (Nasim); P.D.P. Pharoah (Paul); K. Michailidou (Kyriaki); J.P. Tyrer (Jonathan); M.N. Brook (Mark N.); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); A.M. Dunning (Alison); M. Shah (Mitul); R.N. Luben (Robert); J. Brown (Judith); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune F.); H. Flyger (Henrik); K. Czene (Kamila); H. Darabi (Hatef); M. Eriksson (Mikael); J. Peto (Julian); I. dos Santos Silva (Isabel); F. Dudbridge (Frank); N. Johnson (Nichola); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Verhoef; E.J. Rutgers (Emiel J.); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); L.A. Brinton (Louise); J. Lissowska (Jolanta); F.J. Couch (Fergus); J.E. Olson (Janet); C. Vachon (Celine); V.S. Pankratz (Shane); D. Lambrechts (Diether); H. Wildiers (Hans); C. van Ongeval (Chantal); E. van Limbergen (Erik); V. Kristensen (Vessela); G. Grenaker Alnæs (Grethe); S. Nord (Silje); A.-L. Borresen-Dale (Anne-Lise); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P.A. Fasching (Peter); L. Haeberle (Lothar); A.B. Ekici (Arif); M.W. Beckmann (Matthias); B. Burwinkel (Barbara); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); A. Trentham-Dietz (Amy); P. Newcomb (Polly); L. Titus (Linda); K.M. Egan (Kathleen M.); D. Hunter (David); S. Lindstrom (Stephen); R. Tamimi (Rulla); P. Kraft (Peter); N. Rahman (Nazneen); C. Turnbull (Clare); A. Renwick (Anthony); S. Seal (Sheila); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); J. Benítez (Javier); M.P. Zamora (Pilar); J.I. Arias Pérez (José Ignacio); P. Menéndez (Primitiva); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); T. Dörk (Thilo); H. Anton-Culver (Hoda); S.L. Neuhausen (Susan); A. Ziogas (Argyrios); L. Bernstein (Leslie); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); E.K. Khusnutdinova (Elza); M. Bermisheva (Marina); D. Prokofyeva (Darya); Z. Takhirova (Zalina); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Sutter (Christian); R. Yang (Rongxi); P. Schürmann (Peter); M. Bremer (Michael); H. Christiansen (Hans); T.-W. Park-Simon; P. Hillemanns (Peter); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); M. Sanchez (Marie); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); V. Pensotti (Valeria); J. Hopper (John); H. Tsimiklis (Helen); C. Apicella (Carmel); M.C. Southey (Melissa); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); A.J. Sigurdson (Alice); M.M. Doody (Michele M.); U. Hamann (Ute); D. Torres (Diana); H.U. Ulmer (Hans); A. Försti (Asta); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A. Marie Mulligan (Anna); G. Chenevix-Trench (Georgia); R. Balleine (Rosemary); G.G. Giles (Graham); R.L. Milne (Roger); C.A. McLean (Catriona Ann); A. Lindblom (Annika); S. Margolin (Sara); C.A. Haiman (Christopher); B.E. Henderson (Brian); F. Schumacher (Fredrick); L. Le Marchand (Loic); U. Eilber (Ursula); S. Wang-Gohrke (Shan); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); L.B. Koppert (Linetta); J. Carpenter (Jane); C. Clarke (Christine); R.J. Scott (Rodney J.); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); H. Brenner (Hermann); V. Arndt (Volker); C. Stegmaier (Christa); A. Karina Dieffenbach (Aida); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); K. Offit (Kenneth); J. Vijai (Joseph); M. Robson (Mark); R. Rau-Murthy (Rohini); M. Dwek (Miriam); R. Swann (Ruth); K. Annie Perkins (Katherine); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); D. Eccles (Diana); W. Tapper (William); M. Rafiq (Meena); E.M. John (Esther M.); A.S. Whittemore (Alice); S. Slager (Susan); D. Yannoukakos (Drakoulis); A.E. Toland (Amanda); S. Yao (Song); W. Zheng (Wei); S.L. Halverson (Sandra L.); A. González-Neira (Anna); G. Pita (G.); M. Rosario Alonso; N. Álvarez (Nuria); D. Herrero (Daniel); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); M. Maranian (Melanie); S. Healey (Sue); J. Simard (Jacques); P. Hall (Per); D.F. Easton (Douglas); M. García-Closas (Montserrat)
textabstractBackground: 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 l
Dana M Brantley-Sieders
Full Text Available Pre-clinical studies provide compelling evidence that Eph family receptor tyrosine kinases (RTKs and ligands promote cancer growth, neovascularization, invasion, and metastasis. Tumor suppressive roles have also been reported for the receptors, however, creating a potential barrier for clinical application. Determining how these observations relate to clinical outcome is a crucial step for translating the biological and mechanistic data into new molecularly targeted therapies. We investigated eph and ephrin expression in human breast cancer relative to endpoints of overall and/or recurrence-free survival in large microarray datasets. We also investigated protein expression in commercial human breast tissue microarrays (TMA and Stage I prognostic TMAs linked to recurrence outcome data. We found significant correlations between ephA2, ephA4, ephA7, ephB4, and ephB6 and overall and/or recurrence-free survival in large microarray datasets. Protein expression in TMAs supported these trends. While observed no correlation between ephrin ligand expression and clinical outcome in microarray datasets, ephrin-A1 and EphA2 protein co-expression was significantly associated with recurrence in Stage I prognostic breast cancer TMAs. Our data suggest that several Eph family members are clinically relevant and tractable targets for intervention in human breast cancer. Moreover, profiling Eph receptor expression patterns in the context of relevant ligands and in the context of stage may be valuable in terms of diagnostics and treatment.
Full Text Available 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 p53R273H (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.
Full Text Available Abstract Background Basal-like carcinoma are aggressive breast cancers that frequently carry p53 inactivating mutations, lack estrogen receptor-α (ERα and express the cancer stem cell markers CD133 and CD44. These tumors also over-express Interleukin 6 (IL-6, a pro-inflammatory cytokine that stimulates the growth of breast cancer stem/progenitor cells. Results Here we show that p53 deficiency in breast cancer cells induces a loss of methylation at IL-6 proximal promoter region, which is maintained by an IL-6 autocrine loop. IL-6 also elicits the loss of methylation at the CD133 promoter region 1 and of CD44 proximal promoter, enhancing CD133 and CD44 gene transcription. In parallel, IL-6 induces the methylation of estrogen receptor (ERα promoter and the loss of ERα mRNA expression. Finally, IL-6 induces the methylation of IL-6 distal promoter and of CD133 promoter region 2, which harbour putative repressor regions. Conclusion We conclude that IL-6, whose methylation-dependent autocrine loop is triggered by the inactivation of p53, induces an epigenetic reprogramming that drives breast carcinoma cells towards a basal-like/stem cell-like gene expression profile.
Insalaco, Lavinia; Incorvaia, Lorena; Barraco, Nadia; Castiglia, Marta; Rizzo, Sergio; Santini, Daniele; Giordano, Antonio; Castorina, Sergio; Russo, Antonio
Zoledronic acid (ZOL), belonging to third generation bisphosphonate family, is a potent inhibitor of osteoclast-mediated bone resorption, widely used to effectively prevent osteolysis in breast cancer patients who develop bone metastases. Low doses of ZOL have been shown to exhibit a direct anticancer role, by inhibiting cell adhesion, invasion, cytoskeleton remodelling and proliferation in MCF-7 breast cancer cells. In order to identify the molecular mechanisms and signaling pathways underlying the anticancer activity exerted by ZOL, we analyzed for the first time the microRNA expression profile in breast cancer cells. A large-scale microarray analysis of 377 miRNAs was performed on MCF7 cells treated with 10 μM ZOL for 24 h compared to untreated cells. Furthermore, the expression of specific ZOL-induced miRNAs was analyzed in MCF-7 and SkBr3 cells through Real-time PCR. Low-dose treatment with ZOL significantly altered expression of 54 miRNAs. Nine upregulated and twelve downregulated miRNAs have been identified after 24 h of treatment. Also, ZOL induced expression of 11 specific miRNAs and silenced expression of 22 miRNAs. MiRNA data analysis revealed the involvement of differentially expressed miRNAs in PI3K/Akt, MAPK, Wnt, TGF-β, Jak-STAT and mTOR signaling pathways, and regulation of actin cytoskeleton. Our results have been shown to be perfectly coherent with the recent findings reported in literature concerning changes in expression of some miRNAs involved in bone metastasis formation, progression, therapy resistance in breast cancer. In conclusion, this data supports the hypothesis that ZOL-induced modification of the miRNA expression profile contributes to the anticancer efficacy of this agent. PMID:27081088
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
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.
Chu, Andy; Robertson, Gordon; Brooks, Denise; Mungall, Andrew J; Birol, Inanc; Coope, Robin; Ma, Yussanne; Jones, Steven; Marra, Marco A
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.
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.
Sørensen, Kristina P; Thomassen, Mads; Tan, Qihua;
INTRODUCTION: Patients with clinically and pathologically similar breast tumors often have very different outcomes and treatment responses. Current prognostic markers allocate the majority of breast cancer patients to the high-risk group, yielding high sensitivities in expense of specificities be...... cancer patients eligible for adjuvant therapy, as well as early breast cancer patients that could avoid unnecessary systemic adjuvant therapy. This study emphasizes the potential role of lncRNAs in breast cancer prognosis.......INTRODUCTION: Patients with clinically and pathologically similar breast tumors often have very different outcomes and treatment responses. Current prognostic markers allocate the majority of breast cancer patients to the high-risk group, yielding high sensitivities in expense of specificities...... of traditional prognostic markers and time to metastasis. CONCLUSIONS: To our knowledge, this is the first study investigating the prognostic potential of lncRNA profiles. Our study suggest that lncRNA profiles provide additional prognostic information and may contribute to the identification of early breast...
Judith Y.M.N. Engwegen
Full Text Available Colorectal cancer (CRC is the second most common cause of cancer-related death in Europe and its prognosis is largely dependent on stage at diagnosis. Currently, there are no suitable tumour markers for early detection of CRC. In a retrospective study we previously found discriminative CRC serum protein profiles with surface enhanced laser desorption ionisation—time of flight mass spectrometry (SELDI-TOF MS. We now aimed at prospective validation of these profiles. Additionally, we assessed their applicability for follow-up after surgery and investigated tissue protein profiles of patients with CRC and adenomatous polyps (AP. Serum and tissue samples were collected from patients without known malignancy with an indication for colonoscopy and patients with AP and CRC during colonoscopy. Serum samples of controls (CON; n = 359, patients with AP (n = 177 and CRC (n = 73, as well as tissue samples from AP (n = 52 and CRC (n = 47 were analysed as described previously. Peak intensities were compared by non-parametric testing. Discriminative power of differentially expressed proteins was assessed with support vector machines (SVM. We confirmed the decreased serum levels of apolipoprotein C-1 in CRC in the current population. No differences were observed between CON and AP. Apolipoprotein C-I levels did not change significantly within 1 month post-surgery, although a gradual return to normal levels was observed. Several proteins differed between AP and CRC tissue, among which a peak with similar mass as apolipoprotein C-1. This peak was increased in CRC compared to AP. Although we prospectively validated the serum decrease of apolipoprotein C-1 in CRC, serum protein profiles did not yield SVM classifiers with suitable sensitivity and specificity for classification of our patient groups.
Leong, Sharon; Nunez, Andrea C; Lin, Mike Z; Crossett, Ben; Christopherson, Richard I; Baxter, Robert C
Breast cancer is a molecularly heterogeneous disease, and predicting response to chemotherapy remains a major clinical challenge. To minimize adverse side-effects or cumulative toxicity in patients unlikely to benefit from treatment, biomarkers indicating treatment efficacy are critically needed. iTRAQ labeling coupled with multidimensional LC-MS/MS of the enriched mitochondria and endoplasmic reticulum fraction, key organelles regulating apoptosis, has led to the discovery of several differentially abundant proteins in breast cancer cells treated with the chemotherapeutic agent doxorubicin followed by the death receptor ligand, TRAIL, among 571 and 801 unique proteins identified in ZR-75-1 and MDA-MB-231 breast cancer cell lines, respectively. The differentially abundant proteins represent diverse biological processes associated with cellular assembly and organization, molecular transport, oxidative stress, cell motility, cell death, and cancer. Despite many differences in molecular phenotype between the two breast cancer cell lines, a comparison of their subproteomes following drug treatment revealed three proteins displaying common regulation: PPIB, AHNAK, and SLC1A5. Changes in these proteins, detected by iTRAQ, were confirmed by immunofluorescence, visualized by confocal microscopy. These novel potential biomarkers may have clinical utility for assessing response to cancer treatment and may provide insight into new therapeutic targets for breast cancer.
Full Text Available Breast cancer accounts for the largest number of newly diagnosed cases in female cancer patients. Although mammography is a powerful screening tool, about 20% of breast cancer cases cannot be detected by this method. New diagnostic biomarkers for breast cancer are necessary. Here, we used a mass spectrometry-based quantitative metabolomics method to analyze plasma samples from 55 breast cancer patients and 25 healthy controls. A number of 30 patients and 20 age-matched healthy controls were used as a training dataset to establish a diagnostic model and to identify potential biomarkers. The remaining samples were used as a validation dataset to evaluate the predictive accuracy for the established model. Distinct separation was obtained from an orthogonal partial least squares-discriminant analysis (OPLS-DA model with good prediction accuracy. Based on this analysis, 39 differentiating metabolites were identified, including significantly lower levels of lysophosphatidylcholines and higher levels of sphingomyelins in the plasma samples obtained from breast cancer patients compared with healthy controls. Using logical regression, a diagnostic equation based on three metabolites (lysoPC a C16:0, PC ae C42:5 and PC aa C34:2 successfully differentiated breast cancer patients from healthy controls, with a sensitivity of 98.1% and a specificity of 96.0%.
ALAOUI-JAMALI Moulay A.; XU Ying-jie
The progress in the understanding of cancer progression and early detection has been slow and frustrating due to the complex multifactorial nature and heterogeneity of the cancer syndrome. To date, no effective treatment is available for advanced cancers, which remain a major cause of morbidity and mortality. Clearly, there is urgent need to unravel novel biomarkers for early detection.Most of the functional information of the cancer-associated genes resides in the proteome. The later is an exceptionally complex biological system involving several proteins that function through posttranslational modifications and dynamic intermolecular collisions with partners. These protein complexes can be regulated by signals emanating from cancer cells, their surrounding tissue microenvironment, and/or from the host. Some proteins are secreted and/or cleaved into the extracellular milieu and may represent valuable serum biomarkers for diagnosis purpose. It is estimated that the cancer proteome may include over 1.5million proteins as a result of posttranslational processing and modifications. Such complexity clearly highlights the need for ultra-high resolution proteomic technology for robust quantitative protein measurements and data acquisition. This review is to update the current research efforts in high-resolution proteomic technology for discovery and monitoring cancer biomarkers.
Full Text Available Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders. Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11 and non-responders (n = 16 to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029 gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with
Abnormal lipid metabolisms are closely associated with cancers. In this study, mass spectrometry was employed to in situ investigate the associations of membrane lipid phenotypes of six human lung cancer cell lines (i.e., A549, H1650, H1975 from adenocarcinoma, H157 and H1703 from squamous cell carcinomas, and H460 from a large cell carcinoma) with cancer cell types and finally total 230 lipids were detected. Based these 230 lipids, partial least-square discriminant analysis indicated that fi...
M. W. Wille, Mathilde; Dirksen, Asger; Ashraf, Haseem;
RATIONALE: As of April 2015, participants in the Danish Lung Cancer Screening Trial had been followed for at least 5 years since their last screening. OBJECTIVES: Mortality, causes of death, and lung cancer findings are reported to explore the effect of computed tomography (CT) screening. METHODS...... fewer deaths in the screening group. CONCLUSIONS: No statistically significant effects of CT screening on lung cancer mortality were found, but the results of post hoc high-risk subgroup analyses showed nonsignificant trends that seem to be in good agreement with the results of the National Lung...
Jeong, Rae Ung; Lim, Sangsoo; Kim, Myoung Ok; Moon, Myeong Hee
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.
Fisher CM; Schefter TE
Christine M Fisher, Tracey E Schefter Department of Radiation Oncology, University of Colorado, Denver, CO, USA Abstract: 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 occurr...
This work proposes a method to assess the molecular profile of perioperative circulating tumor cells in peripheral blood (PB) of colorectal cancer patients for differentiating the dissemination process of tumor cells. Two-point quantification of multiple marker genes was designed for describing the profile. The expression levels of cytokeratin 20 (CK20),carcino-embryonic antigen (CEA) and survivin mRNA in PB and tumor tissue samples in 37 colorectal cancer patients from 1 d pre-operation to 2 h postoperation were detected with real-time quantitative reverse transcription-polymerase chain reaction. β-Actin mRNA was used as internal control to standardize the results of different mRNA expression levels. The data analysis using Stata statistical packages,Chi-Square test and Mann-Whitney test indicated the expression level of CEA mRNA in PB increased significantly,while those of CK20 and survivin mRNA decreased significantly. Quantitative comparison with tumor tissues indicated that the increase of CEA mRNA level in PB coincided with the decrease of CK20 and survivin mRNA levels in different tumor cells. These results showed surgical manipulation caused tumor cells shedding into blood from primary tumor tissue and significant increase of CEA mRNA level,while occult tumor cells with high expression levels of CK20 and survivin mRNA before surgery decreased after surgery.
Haddock, Robert L.; Olson, David R.; Backer, Lorraine; Malilay, Josephine
We reviewed patient records with a first-listed diagnosis of urolithiasis—also known as urinary tract or kidney stone disease, nephrolithiasis—upon discharge from Guam’s sole civilian hospital during 2006 to 2010 and urinary cancer mortality records from the Guam Cancer Registry for 1970 to 2009 to determine the source of municipal water supplied to the patients’ residence. The objective was to investigate a possible relationship between the sources of municipal water supplied to Guam villages and the incidence of urolithiasis and urinary cancer. We analyzed hospital discharge diagnoses of urolithiasis or renal calculi by calculating the incidence of first-mentioned discharge for urolithiasis or renal calculi and comparing rates across demographic or geographic categories while adjusting by age, sex, and ethnicity/race. We reviewed cancer registry records of urinary cancer deaths by patient residence. The annual incidence of hospitalization for urolithiasis was 5.22 per 10,000. Rates adjusted for sex or age exhibited almost no change. The rate of 9.83 per 10,000 among Chamorros was significantly higher (p < 0.05) than the rates among any other ethnic group or race. When villages were grouped by water source, rates of patients discharged with a first-listed diagnosis of urolithiasis, adjusted for ethnicity/race, were similar for villages using either well water (5.44 per 10,000) or mixed source water (5.39 per 10,000), and significantly greater than the rate for villages using exclusively reservoir water (1.35 per 10,000). No statistically significant differences were found between the water source or village of residence and urinary cancer mortality. Some Guam residents living in villages served completely or partly by deep well water high in calcium carbonate may be at increased risk for urolithiasis compared with residents living in villages served by surface waters. Although the risk appears to be highest in villagers of Chamorro ethnicity, residents
Haddock, Robert L; Olson, David R; Backer, Lorraine; Malilay, Josephine
We reviewed patient records with a first-listed diagnosis of urolithiasis-also known as urinary tract or kidney stone disease, nephrolithiasis-upon discharge from Guam's sole civilian hospital during 2006 to 2010 and urinary cancer mortality records from the Guam Cancer Registry for 1970 to 2009 to determine the source of municipal water supplied to the patients' residence. The objective was to investigate a possible relationship between the sources of municipal water supplied to Guam villages and the incidence of urolithiasis and urinary cancer. We analyzed hospital discharge diagnoses of urolithiasis or renal calculi by calculating the incidence of first-mentioned discharge for urolithiasis or renal calculi and comparing rates across demographic or geographic categories while adjusting by age, sex, and ethnicity/race. We reviewed cancer registry records of urinary cancer deaths by patient residence. The annual incidence of hospitalization for urolithiasis was 5.22 per 10,000. Rates adjusted for sex or age exhibited almost no change. The rate of 9.83 per 10,000 among Chamorros was significantly higher (p < 0.05) than the rates among any other ethnic group or race. When villages were grouped by water source, rates of patients discharged with a first-listed diagnosis of urolithiasis, adjusted for ethnicity/race, were similar for villages using either well water (5.44 per 10,000) or mixed source water (5.39 per 10,000), and significantly greater than the rate for villages using exclusively reservoir water (1.35 per 10,000). No statistically significant differences were found between the water source or village of residence and urinary cancer mortality. Some Guam residents living in villages served completely or partly by deep well water high in calcium carbonate may be at increased risk for urolithiasis compared with residents living in villages served by surface waters. Although the risk appears to be highest in villagers of Chamorro ethnicity, residents should be
Robert L. Haddock
Full Text Available We reviewed patient records with a first-listed diagnosis of urolithiasis—also known as urinary tract or kidney stone disease, nephrolithiasis—upon discharge from Guam’s sole civilian hospital during 2006 to 2010 and urinary cancer mortality records from the Guam Cancer Registry for 1970 to 2009 to determine the source of municipal water supplied to the patients’ residence. The objective was to investigate a possible relationship between the sources of municipal water supplied to Guam villages and the incidence of urolithiasis and urinary cancer. We analyzed hospital discharge diagnoses of urolithiasis or renal calculi by calculating the incidence of first-mentioned discharge for urolithiasis or renal calculi and comparing rates across demographic or geographic categories while adjusting by age, sex, and ethnicity/race. We reviewed cancer registry records of urinary cancer deaths by patient residence. The annual incidence of hospitalization for urolithiasis was 5.22 per 10,000. Rates adjusted for sex or age exhibited almost no change. The rate of 9.83 per 10,000 among Chamorros was significantly higher (p < 0.05 than the rates among any other ethnic group or race. When villages were grouped by water source, rates of patients discharged with a first-listed diagnosis of urolithiasis, adjusted for ethnicity/race, were similar for villages using either well water (5.44 per 10,000 or mixed source water (5.39 per 10,000, and significantly greater than the rate for villages using exclusively reservoir water (1.35 per 10,000. No statistically significant differences were found between the water source or village of residence and urinary cancer mortality. Some Guam residents living in villages served completely or partly by deep well water high in calcium carbonate may be at increased risk for urolithiasis compared with residents living in villages served by surface waters. Although the risk appears to be highest in villagers of Chamorro
Full Text Available Abstract Background Development of innovative, effective therapies against recurrent/chemotherapy-resistant ovarian cancer remains a high priority. Using high-throughput technologies to analyze genetic fingerprints of ovarian cancer, we have discovered extremely high expression of the genes encoding the proteins claudin-3 and claudin-4. Methods Because claudin-3 and -4 are the epithelial receptors for Clostridium perfringens enterotoxin (CPE, and are sufficient to mediate CPE binding, in this study we evaluated the in vitro and in vivo bioactivity of the carboxy-terminal fragment of CPE (i.e., CPE290-319 binding peptide as a carrier for tumor imaging agents and intracellular delivery of therapeutic drugs. Claudin-3 and -4 expression was examined with rt-PCR and flow cytometry in multiple primary ovarian carcinoma cell lines. Cell binding assays were used to assess the accuracy and specificity of the CPE peptide in vitro against primary chemotherapy-resistant ovarian carcinoma cell lines. Confocal microscopy and biodistribution assays were performed to evaluate the localization and uptake of the FITC-conjugated CPE peptide in established tumor tissue. Results Using a FITC-conjugated CPE peptide we show specific in vitro and in vivo binding to multiple primary chemotherapy resistant ovarian cancer cell lines. Bio-distribution studies in SCID mice harboring clinically relevant animal models of chemotherapy resistant ovarian carcinoma showed higher uptake of the peptide in tumor cells than in normal organs. Imunofluorescence was detectable within discrete accumulations (i.e., tumor spheroids or even single chemotherapy resistant ovarian cancer cells floating in the ascites of xenografted animals while a time-dependent internalization of the FITC-conjugated CPE peptide was consistently noted in chemotherapy-resistant ovarian tumor cells by confocal microscopy. Conclusions Based on the high levels of claudin-3 and -4 expression in chemotherapy
Full Text Available Lung cancer is the most common form of cancer with the highest incidence worldwide. The mortality rates are highest in males and second highest in females, after breast cancer. The genetic predisposition to Non Small Cell Lung Cancer (NSCLC is still under investigation, however, studies have shown that the Epidermal Growth Factor Receptor (EGFR, a receptor tyrosine kinase is frequently over-expressed and activated to a phosphorylated state in NSCLC. The activity of EGFR in cancer cells results in the phosphorylation of downstream proteins that promote cell proliferation, invasion, metastasis, and inhibition of apoptosis. Targeting the EGFR pathway therefore constitutes a relevant strategy for cancer therapy. Gefitinib is a selective inhibitor of the EGFR tyrosine kinase and is indicated for the treatment of adult patients with locally advanced or metastatic NSCLC with activating mutations of EGFR-TK. From the pharmacoeconomic point of view gefitinib is dominant (more effective and less expensive compared to the alternatives. In conclusion, gefitinib is a treatment option for NSCLC tumors with a high clinical and economic value in the Italian setting.
Full Text Available Mark W Burns, Eric S Kim Wilmot Cancer Center, University of Rochester, Rochester, NY, USA Abstract: Lung cancer has become one of the leading causes of death in both men and women in the United States, with approximately 230,000 new cases and 160,000 deaths each year. Approximately 80% of lung cancer patients are diagnosed with non-small-cell lung cancer (NSCLC, a subset of epithelial lung cancers that are generally insensitive to chemotherapy. An estimated 3%–7% of NSCLC patients harbor tumors containing anaplastic lymphoma kinase (ALK gene rearrangement as an oncogenic driver. Subsequent development of the first-generation tyrosine kinase inhibitor crizotinib demonstrated substantial initial ALK+-tumor regression, yet ultimately displayed resistance in treated patients. The recently approved tyrosine kinase inhibitor ceritinib has been shown to be an effective antitumor agent against crizotinib-naïve and -resistant ALK+-NSCLC patients. In this review, we will provide an overview of biology and management of ALK+-NSCLC with a special focus on clinical development of ceritinib. Keywords: ceritinib, anaplastic lymphoma kinase, non-small-cell lung cancer
Gang-Qiang Li; Hao Li; Hong-Fu Zhang
AIM: To investigate the expression of tumor suppressor gene p53 and spindle checkpoint gene Mad2, and to demonstrate their expression difference in colorectal cancer and normal mucosa and to evaluate its clinical significance.METHODS: Westemn blot and immunohistochemistry methods were used to analyze the expression of Mad2 in colorectal cancer and its corresponding normal mucosa. The expression of p53 was detected by immunohistochemistry method in colorectal cancer and its corresponding normal mucosa.RESULTS: Mad2 was significantly overexpressed in colorectal cancer compared with corresponding normal mucosa (P＜0.001), and it was not related to the differentiation of adenocarcinoma and other dinical factors (P＞0.05).The ratio of Mad2 protein in cancer tissue (C) to that in its normal mucosa tissue (N) was higher than 2, which was more frequently observed in patients with lymph gland metastasis (P＜0.05). p53 protein expression was not observed in normal mucosa. The rate of p53 positive expression in adenocarcinomas was 52.6%. There was a significant difference between adenocarcinomas and normal mucosa(P＜0.001), which was not related to the differentiation degree of adenocarcinoma and other clinical factors (P＞0.05).CONCLUSION: Defect of spindle checkpoint gene Mad2and mutation of p53 gene are involved mainly in colorectal carcinogenesis and C/N＞2 is associated with prognosis of colorectal cancer.
Full Text Available Amanda L Richer,1 Jacqueline M Friel,1 Vashti M Carson,2 Landon J Inge,1 Timothy G Whitsett2 1Norton Thoracic Institute, St Joseph’s Hospital and Medical Center, 2Cancer and Cell Biology Division, Translational Genomics Research Institute, Phoenix, AZ, USA Abstract: Lung cancer remains the leading cause of cancer-related mortality worldwide. The application of next-generation genomic technologies has offered a more comprehensive look at the mutational landscape across the different subtypes of non-small cell lung cancer (NSCLC. A number of recurrent mutations such as TP53, KRAS, and epidermal growth factor receptor (EGFR have been identified in NSCLC. While targeted therapeutic successes have been demonstrated in the therapeutic targeting of EGFR and ALK, the majority of NSCLC tumors do not harbor these genomic events. This review looks at the current treatment paradigms for lung adenocarcinomas and squamous cell carcinomas, examining genomic aberrations that dictate therapy selection, as well as novel therapeutic strategies for tumors harboring mutations in KRAS, TP53, and LKB1 which, to date, have been considered “undruggable”. A more thorough understanding of the molecular alterations that govern NSCLC tumorigenesis, aided by next-generation sequencing, will lead to targeted therapeutic options expected to dramatically reduce the high mortality rate observed in lung cancer. Keywords: non-small cell lung cancer, precision medicine, epidermal growth factor receptor, Kirsten rat sarcoma viral oncogene homolog, serine/threonine kinase 11, tumor protein p53
El Fatemi Hinde
Full Text Available Abstract Background Breast cancer may be classified into luminal A, luminal B, HER2+/ER-, basal-like and normal-like subtypes based on gene expression profiling or immunohistochemical (IHC characteristics. The aim of our study is to show the molecular profile characteristic of breast cancer in the North African population of Morocco. This work showed preliminary results and correlations with clinicopathological and histological parameters. Three hundred and ninety primary breast carcinomas tumor tissues were immunostained for ER, PR, HER2, CK5/6, CK8/18 and Ki67 using paraffin tissue. Methods We reviewed 390 cases of breast cancer diagnosed on January 2008 to December 2011 at the Department of pathology, Hassan II teaching hospital, Fez, Morocco. Age, size tumor, metastatic profile, node involvement profile, histological type and immunohistochemical profile were studied. Results The average age was 46 years; our patients were diagnosed late with a high average tumor size. Luminal B subtype was more prevalent (41.8%, followed by luminal A (30.5%, basal-like (13, 6%, Her2-overexpressing (9, 2%, and unclassified subtype (4.9%. Conclusion This study showed that molecular classification and biological profile may be different according to geographical distribution, to encourage further studies to know the genomic profile of tumors and the environment. Virtual slide http://www.diagnosticpathology.diagnomx.eu/vs/1675272504826544
Saleh M Rachidi
Full Text Available 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
Allocca Hernandez, Giacomo Antonio
Getting old involves a lot of changes in life. Family and social relations change and mobility can decrease. These variations require new settings, and of course special care. A nursing home is a place dedicated to help with this situation. Sometimes nursing homes can be perceived as mere institutions by society, and even by future residents. Inside, senior citizens are suppose to spend the rest of their lives doing the same activities day after day. How can we improve these days? Archite...
Alevizos, Leonidas; Kataki, Agapi; Derventzi, Anastasia; Gomatos, Ilias; Loutraris, Christos; Gloustianou, Georgia; Manouras, Andreas; Konstadoulakis, Manousos M; Zografos, George
DNA methylation is the best characterised epigenetic change so far. However, its role in breast cancer metastasis has not as yet been elucidated. The aim of this study was to investigate the differences between the methylation profiles characterising primary tumours and their corresponding positive or negative for metastasis lymph nodes (LN) and correlate these with tumour metastatic potential. Methylation signatures of Caveolin-1, CXCR4, RAR-β, Cyclin D2 and Twist gene promoters were studied in 30 breast cancer primary lesions and their corresponding metastasis-free and tumour-infiltrated LN with Methylation-Specific PCR. CXCR4 and Caveolin-1 expression was further studied by immunohistochemistry. Tumours were typified by methylation of RAR-β and hypermethylation of Cyclin-D2 and Twist gene promoters. Tumour patterns were highly conserved in tumour-infiltrated LN. CXCR4 and Caveolin-1 promoter methylation patterns differentiated between node-negative and metastatic tumours. Nodal metastasis was associated with tumour and lymph node profiles of extended methylation of Caveolin-1 and lack of CXCR4 hypermethylation. Immunodetection studies verified CXCR4 and Caveolin-1 hypermethylation as gene silencing mechanism. Absence of Caveolin-1 expression in stromal cells associated with tumour aggressiveness while strong Caveolin-1 expression in tumour cells correlated with decreased 7-year disease-free survival. Methylation-mediated activation of CXCR4 and inactivation of Caveolin-1 was linked with nodal metastasis while intratumoral Caveolin-1 expression heterogeneity correlated with disease progression. This evidence contributes to the better understanding and, thereby, therapeutic management of breast cancer metastasis process.
Full Text Available FDA-cleared ovarian cancer biomarkers are limited to CA-125 and HE4 for monitoring and recurrence and OVA1, a multivariate panel consisting of CA-125 and four additional biomarkers, for referring patients to a specialist. Due to relatively poor performance of these tests, more accurate and broadly applicable biomarkers are needed. We evaluated the dysregulation of 259 candidate cancer markers in serum samples from 499 patients. Sera were collected prospectively at 11 monitored sites under a single well-defined protocol. All stages of ovarian cancer and common benign gynecological conditions were represented. To ensure consistency and comparability of biomarker comparisons, all measurements were performed on a single platform, at a single site, using a panel of rigorously calibrated, qualified, high-throughput, multiplexed immunoassays and all analyses were conducted using the same software. Each marker was evaluated independently for its ability to differentiate ovarian cancer from benign conditions. A total of 175 markers were dysregulated in the cancer samples. HE4 (AUC=0.933 and CA-125 (AUC=0.907 were the most informative biomarkers, followed by IL-2 receptor α, α1-antitrypsin, C-reactive protein, YKL-40, cellular fibronectin, CA-72-4 and prostasin (AUC>0.800. To improve the discrimination between cancer and benign conditions, a simple multivariate combination of markers was explored using logistic regression. When combined into a single panel, the nine most informative individual biomarkers yielded an AUC value of 0.950, significantly higher than obtained when combining the markers in the OVA1 panel (AUC 0.912. Additionally, at a threshold sensitivity of 90%, the combination of the top 9 markers gave 88.9% specificity compared to 63.4% specificity for the OVA1 markers. Although a blinded validation study has not yet been performed, these results indicate that alternative biomarker combinations might lead to significant improvements in the
Full Text Available Abstract Background Changes in DNA methylation of crucial cancer genes including tumor suppressors can occur early in carcinogenesis, being potentially important early indicators of cancer. The objective of this study was to examine a multiplexed approach to assess the methylation of tumor suppressor genes as tumor stratification and clinical outcome prognostic biomarkers for lung cancer. Methods A multicandidate probe panel interrogated DNA for aberrant methylation status in 18 tumor suppressor genes in lung cancer using a methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA. Lung cancer cell lines (n = 7, and primary lung tumors (n = 54 were examined using MS-MLPA. Results Genes frequently methylated in lung cancer cell lines including SCGB3A1, ID4, CCND2 were found among the most commonly methylated in the lung tumors analyzed. HLTF, BNIP3, H2AFX, CACNA1G, TGIF, ID4 and CACNA1A were identified as novel tumor suppressor candidates methylated in lung tumors. The most frequently methylated genes in lung tumors were SCGB3A1 and DLC1 (both 50.0%. Methylation rates for ID4, DCL1, BNIP3, H2AFX, CACNA1G and TIMP3 were significantly different between squamous and adenocarcinomas. Methylation of RUNX3, SCGB3A1, SFRP4, and DLC1 was significantly associated with the extent of the disease when comparing localized versus metastatic tumors. Moreover, methylation of HTLF, SFRP5 and TIMP3 were significantly associated with overall survival. Conclusions MS-MLPA can be used for classification of certain types of lung tumors and clinical outcome prediction. This latter is clinically relevant by offering an adjunct strategy for the clinical management of lung cancer patients.
Choudhury, Sibgat; Almendro, Vanessa; Merino, Vanessa F; Wu, Zhenhua; Maruyama, Reo; Su, Ying; Martins, Filipe C; Fackler, Mary Jo; Bessarabova, Marina; Kowalczyk, Adam; Conway, Thomas; Beresford-Smith, Bryan; Macintyre, Geoff; Cheng, Yu-Kang; Lopez-Bujanda, Zoila; Kaspi, Antony; Hu, Rong; Robens, Judith; Nikolskaya, Tatiana; Haakensen, Vilde D; Schnitt, Stuart J; Argani, Pedram; Ethington, Gabrielle; Panos, Laura; Grant, Michael; Clark, Jason; Herlihy, William; Lin, S Joyce; Chew, Grace; Thompson, Erik W; Greene-Colozzi, April; Richardson, Andrea L; Rosson, Gedge D; Pike, Malcolm; Garber, Judy E; Nikolsky, Yuri; Blum, Joanne L; Au, Alfred; Hwang, E Shelley; Tamimi, Rulla M; Michor, Franziska; Haviv, Izhak; Liu, X Shirley; Sukumar, Saraswati; Polyak, Kornelia
Early full-term pregnancy is one of the most effective natural protections against breast cancer. To investigate this effect, we have characterized the global gene expression and epigenetic profiles of multiple cell types from normal breast tissue of nulliparous and parous women and carriers of BRCA1 or BRCA2 mutations. We found significant differences in CD44(+) progenitor cells, where the levels of many stem cell-related genes and pathways, including the cell-cycle regulator p27, are lower in parous women without BRCA1/BRCA2 mutations. We also noted a significant reduction in the frequency of CD44(+)p27(+) cells in parous women and showed, using explant cultures, that parity-related signaling pathways play a role in regulating the number of p27(+) cells and their proliferation. Our results suggest that pathways controlling p27(+) mammary epithelial cells and the numbers of these cells relate to breast cancer risk and can be explored for cancer risk assessment and prevention.
Koo, Kevin M; Wee, Eugene J H; Trau, Matt
Aberrant chromosal rearrangements, such as the multiple variants of TMPRSS2:ERG fusion gene mutations in prostate cancer (PCa), are promising diagnostic and prognostic biomarkers due to their specific expression in cancerous tissue only. Additionally, TMPRSS2:ERG variants are detectable in urine to provide non-invasive PCa diagnostic sampling as an attractive surrogate for needle biopsies. Therefore, rapid and simplistic assays for identifying multiple urinary TMPRSS2:ERG variants are potentially useful to aid in early cancer detection, immediate patient risk stratification, and prompt personalized treatment. However, current strategies for simultaneous detection of multiple gene fusions are limited by tedious and prolonged experimental protocols, thus limiting their use as rapid clinical screening tools. Herein, we report a simple and rapid gene fusion strategy which expliots the specificity of DNA ligase and the speed of isothermal amplification to simultaneously detect multiple fusion gene RNAs within a short sample-to-answer timeframe of 60min. The method has a low detection limit of 2 amol (1000 copies), and was successfully applied for non-invasive fusion gene profiling in patient urine samples with subsequent validation by a PCR-based gold standard approach.
XU Qing-yong; GAO Yuan; LIU Yan; YANG Wei-zhi; XU Xiang-ying
Background Radiotherapy plays a critical role in the management of non-small cell lung cancer (NSCLC). This study was conducted to identify gene expression profiles of acquired radioresistant NSCLC cell line established by fractionated ionizing radiation (FIR) by cDNA microarray.Methods The human lung adenocarcinoma cell line Anip973 was treated with high energy X-ray to receive 60 Gy in 4 Gy fractions. The radiosensitivity of Anip973R and its parental line were measured by clonogenic assay. Gene expression profiles of Anip973R and its parental line were analyzed using cDNA microarray consisting of 21 522 human genes.Identified partly different expressive genes were validated by quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR).Results Fifty-nine upregulated and 43 downregulated genes were identified to radio-resistant Anip973R. Up-regulated genes were associated with DNA damage repair (DDB2), extracellular matrix (LOX), cell adhesion (CDH2), and apoptosis (CRYAB). Down-regulated genes were associated with angiogenesis (GBP-1), immune response (CD83), and calcium signaling pathway (TNNC1). Subsequent validation of selected eleven genes (CD24, DDB2, IGFBP3, LOX,CDH2, CRYAB, PROCR, ANXA1 DCN, GBP-1 and CD83) by Q-RT-PCR was consistent with microarray analysis.Conclusions Fractionated ionizing radiation can lead to the development of radiation resistance. Altered gene profiles of radioresistant cell line may provide new insights into mechanisms underlying clinical radioresistance for NSCLC.
Ferreira, Flávia Regina; Ogawa, Marilia Marufuji; Nascimento, Luiz Fernando Costa; Tomimori, Jane
BACKGROUND Nonmelanoma skin cancer is the most common form of cancer in humans and also the malignant disease that is increasingly common among kidney transplant recipients. OBJECTIVE To determine the epidemiological characteristics of renal transplant recipients with nonmelanoma skin cancer seen at a referral transplantation center. METHODS Cross-sectional descriptive study with renal transplant recipients presenting nonmelanoma skin cancer, treated at a transplantation referral center between 08/01/2004 and 08/31/2009. Analyzed variables were: gender, age, skin phototype, occupational and recreational sun exposure, use of photoprotection, personal and family history of non-melanoma skin cancer, clinical type and location, time between transplantation and the appearance of the first nonmelanoma skin cancer, occurrence of viral warts, timing of transplantation, type of donor, cause of kidney failure, previous transplants, comorbidities, pre-transplant dialysis, type and duration of dialysis. RESULTS 64 subjects were included. Males - 71.9%; low skin phototypes (up to Fitzpatrick III) - 89%; mean age - 57.0 years - and mean age at transplant - 47.3 years; sun exposure - 67.2% occupational - and 64.1% recreational; photoprotection - 78.2% (although only 34.4% in a regular manner); squamous cell carcinoma - 67.2%; squamous cell carcinoma/basal cell carcinoma ratio - 2:1; personal history of nonmelanoma skin cancer - 25% - and family history - 10.9%; location at photoexposed area - 98.4%; average latency time between transplantation and first nonmelanoma skin cancer appearance - 78.3 months; viral warts (HPV) after transplant - 53.1%; average timing of transplantation - 115.5 months; living donor - 64.1%; triple regimen (antirejection) - 73.2%; comorbidities - 92.2%; pre-transplant dialysis - 98.4%; hemodialysis - 71.7%; average duration of dialysis - 39.1 months; previous transplants - 3.1%; hypertension as cause of renal failure - 46.9%. CONCLUSION This study allowed
Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical Hospital, Taichung, Taiwan (China); Huang, Ya-Li [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Huang, Yung-Kai [School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Chen, Shu-Yuan [Department of Public Health, Tzu-Chi University, Hualien, Taiwan (China); Hsueh, Yu-Mei, E-mail: firstname.lastname@example.org [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)
Few studies investigated the association between chronic arsenic exposure and the mortality of cancers by estimating individual urinary arsenic methylation profiles. Therefore, we compared with the general population in Taiwan to calculate the standardized mortality ratio (SMR) in arseniasis-endemic area of Taiwan from 1996 to 2010 and evaluated the dose-response relationships between environmental arsenic exposure indices or urinary arsenic profiles and the mortality of cause-specific cancer. A cohort of 1563 residents was conducted and collected their urine sample and information regarding arsenic exposure from a questionnaire. All-cause death was identified using the National Death Registry of Taiwan. Urinary arsenic profiles were measured using high performance liquid chromatography–hydride generator–atomic absorption spectrometry. We used Cox proportional hazard models to evaluate the mortality risks. In results, 193 all-site cancer deaths, and 29, 71, 43 deaths respectively for liver, lung and bladder cancers were ascertained. The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. People with high urinary InAs% or low DMA% or low secondary methylation index (SMI) were the most likely to suffer bladder cancer after adjusting other risk factors. Even stopping exposure to arsenic from the artesian well water, the mortality rates of the residents were higher than general population. Finally, urinary InAs%, DMA% and SMI could be the potential biomarkers to predict the mortality risk of bladder cancer. -- Highlights: ► The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. ► People with high urinary InAs% were the most likely to suffer bladder cancer. ► People with low DMA% or low SMI were the most likely to suffer bladder cancer.
Chemometric analysis of the interactions among different parameters describing health conditions, breast cancer risk and fatty acids profile in serum of rats supplemented with conjugated linoleic acids.
Białek, Agnieszka; Zagrodzki, Paweł; Tokarz, Andrzej
We investigated how different doses of conjugated linoleic acids applied for various periods of time influence breast cancer risk and fatty acids profile in serum of rats treated or not with 7,12-dimethylbenz[a]anthracene (DMBA). We also search for interactions among parameters describing health conditions and cancer risk. Animals were divided into 18 groups with different diet modifications (vegetable oil, 1.0%, 2.0% additions of CLA) and different periods of supplementation. In groups treated with DMBA mammary adenocarcinomas appeared. Due to the complexity of experiment apart from statistical analysis a chemometric tool-Partial Least Square method was applied. Analysis of pairs of correlated parameters allowed to identify some regularities concerning the relationships between fatty acid profiles and clinical features of animals. Fatty acids profile was the result of prolonged exposure to high dose of CLA and DMBA administration. These two factors underlined the differences in fatty acids profiles among clusters of animals.
Jochumsen, Kirsten Marie; Tan, Qihua; Høgdall, EV;
toward investigations for more individualized therapies and the use of gene expression profiles in the clinical practice. RNA from tumor tissue from 43 Danish patients with serous epithelial ovarian carcinoma (11 International Federation of Gynecology and Obstetrics [FIGO] stage I/II, 32 FIGO stage III......-term survivors (median overall survival of 32 months) from long-term survivors (median overall survival not yet reached after a median follow-up of 76 months) with a P value of 3.4 x 10 was found. The prognostic gene set was also able to distinguish short-term from long-term survival in patients with advanced......The purpose was to find a gene expression profile that could distinguish short-term from long-term survivors in our collection of serous epithelial ovarian carcinomas. Furthermore, it should be able to stratify in an external validation set. Such a classifier profile will take us a step forward...
Full Text Available Pancreatic ductal adenocarcinoma is characterized by a prominent fibroinflammatory stroma with both tumor-promoting and tumor-suppressive functions. The pancreatic stellate cell (PSC is the major cellular stromal component and the main producer of extracellular matrix proteins, including collagens, which are degraded by metalloproteinases (MMPs. PSCs interact with cancer cells through various factors, including transforming growth factor (TGFβ and interleukin (IL-1α. The role of TGFβ in the dual nature of tumor stroma, i.e., protumorigenic or tumor suppressive, is not clear. We aimed to investigate the roles of TGFβ and IL-1α in the regulation of MMP profiles in PSCs and the subsequent effects on cancer cell migration. Human PSCs isolated from surgically resected specimens were cultured in the presence of pancreatic cancer cell lines, as well as IL-1α or TGFβ. MMP production and activities in PSCs were quantified by gene array transcripts, mRNA measurements, fluorescence resonance energy transfer–based activity assay, and zymography. PSC-conditioned media and pancreatic cancer cells were included in a collagen matrix cell migration model. We found that production of IL-1α by pancreatic cancer cells induced alterations in MMP and tissue inhibitors of matrix metalloproteinase (TIMP profiles and activities in PSCs, upregulated expression and activation of MMP1 and MMP3, and enhanced migration of pancreatic cancer cells in the collagen matrix model. TGFβ counteracted the effects of IL-1α on PSCs, reestablished PSC MMP and TIMP profiles and activities, and inhibited migration of cancer cells. This suggests that tumor TGFβ has a role as a suppressor of stromal promotion of tumor progression through alterations in PSC MMP profiles with subsequent inhibition of pancreatic cancer cell migration.
Laskar, Ruhina Shirin; Ghosh, Sankar Kumar; Talukdar, Fazlur Rahman
Rectal cancer is a heterogeneous disease that develops through multiple pathways characterized by genetic and epigenetic alterations. India has a comparatively higher proportion of rectal cancers and early-onset cases. We analyzed genetic (KRAS, TP53 and BRAF mutations, and MSI), epigenetic alterations (CpG island methylation detection of 10 tumor-related genes/loci), the associated clinicopathological features and survival trend in 80 primary rectal cancer patients from India. MSI was detected using BAT 25 and BAT 26 mononucleotide markers and mutation of KRAS, TP53, and BRAF V600E was detected by direct sequencing. Methyl specific polymerase chain reaction was used to determine promoter methylation status of the classic CIMP panel markers (P16, hMLH1, MINT1, MINT2, and MINT31) as well as other tumor specific genes (DAPK, RASSF1, BRCA1, and GSTP1). MSI and BRAF mutations were uncommon but high frequencies of overall KRAS mutations (67.5%); low KRAS codon 12 and a novel KRAS G15S mutation with concomitant RASSF1 methylation in early onset cases were remarkable. Hierarchical clustering as well as principal component analysis identified three distinct subgroups of patients having discrete age at onset, clinicopathological, molecular and survival characteristics: (i) a KRAS associated CIMP-high subgroup; (ii) a significantly younger MSS, CIMP low, TP53 mutant group having differential KRAS mutation patterns, and (iii) a CIMP-negative, TP53 mutated group. The early onset subgroup exhibited the most unfavorable disease characteristics with advanced stage, poorly differentiated tumors and had the poorest survival compared to the other subgroups. Genetic and epigenetic profiling of rectal cancer patients identified distinct subtypes in Indian population.
Full Text Available Mass spectrometry-based analyses of the low-molecular-weight fraction of serum proteome allow identifying proteome profiles (signatures that are potentially useful in detection and classification of cancer. Several published studies have shown that multipeptide signatures selected in numerical tests have potential values for diagnostics of different types of cancer. However due to apparent problems with standardization of methodological details, both experimental and computational, none of the proposed peptide signatures analyzed directly by MALDI/SELDI-ToF spectrometry has been approved for routine diagnostics. Noteworthy, several components of proposed cancer signatures, especially those characteristic for advanced cancer, were identified as fragments of blood proteins involved in the acute phase and inflammatory response. This indicated that among cancer biomarker candidates to be possibly identified by serum proteome profiling were rather those reflecting overall influence of a disease (and the therapy upon the human organism, than products of cancer-specific genes. Current paper focuses on changes in serum proteome that are related to response of patient’s organism to progressing malignancy and toxicity of anticancer treatment. In addition, several methodological issues that affect robustness and interlaboratory reproducibility of MS-based serum proteome profiling are discussed.
Donnenfeld, Mathilde; Julia, Chantal; Kesse-Guyot, Emmanuelle; Méjean, Caroline; Ducrot, Pauline; Péneau, Sandrine; Deschasaux, Mélanie; Latino-Martel, Paule; Fezeu, Léopold; Hercberg, Serge; Touvier, Mathilde
The Food Standards Agency Nutrient Profiling System (FSA-NPS) constitutes the basis for the Five-Colour Nutrition Label suggested in France to be put on the front-of-pack of food products. At the individual level, a dietary index (FSA-NPS DI) has been derived and validated and corresponds to a weighted mean of all FSA-NPS scores of foods usually consumed by the individual, reflecting the nutritional quality of his/her diet. Our aim was to investigate the association between the FSA-NPS DI and cancer risk in a large cohort. This prospective study included 6435 participants to the SUpplémentation en VItamines et Minéraux AntioXydants cohort (1994-2007) who completed at least six 24 h dietary records during the first 2 years of follow-up. FSA-NPS DI was computed for each subject (higher values representing lower nutritional quality of the diet). After a median follow-up of 12·6 years, 453 incident cancers were diagnosed. Associations were characterised by multivariate Cox proportional hazards models. The FSA-NPS DI was directly associated with overall cancer risk (hazard ratio (HR)for a 1-point increment=1·08 (95 % CI 1·01, 1·15), P trend=0·02; HRQ5 v. Q1=1·34 (95 % CI 1·00, 1·81), P trend=0·03). This association tended to be more specifically observed in subjects with moderate energy intake (≤median, HRfor a 1-point increment=1·10 (95 % CI 1·01-1·20), P trend=0·03). No association was observed in subjects with higher energy intake (P trend=0·3). Results were not statistically significant for breast and prostate cancer risks. For the first time, this study investigated the prospective association between the FSA-NPS individual score and cancer risk. The results suggest that unhealthy food choices may be associated with a 34 % increase in overall cancer risk, supporting the public health relevance of developing front-of-pack nutrition labels based on this score.
Full Text Available Brittany A Davidson, Angeles Alvarez Secord Division of Gynecologic Oncology, Duke Cancer Institute, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA Abstract: Epithelial ovarian cancer (EOC is the most lethal gynecological cancer. Recently, clinical trials have focused on novel antiangiogenic agents in combination with chemotherapy or alone in women with primary and recurrent ovarian cancer. Antiangiogenic agents include monoclonal antibodies, tyrosine-kinase inhibitors, and peptibodies. Many of these agents, including bevacizumab, pazopanib, nintedanib, cediranib, and trebananib, have been evaluated in randomized Phase III clinical trials, and all have demonstrated a progression-free survival (PFS benefit. Specifically, maintenance pazopanib was shown to improve PFS in women with newly diagnosed EOC. Pazopanib, an oral TKI, inhibits several kinase receptors, including those for vascular endothelial growth factor (-1,-2,-3, platelet-derived growth factor (-α and -β, and fibroblast growth factor. It also targets stem cell-factor receptor (c-kit, interleukin 2-inducible T-cell kinase, lymphocyte-specific protein tyrosine kinase, and colony-stimulating factor 1 receptor. Pazopanib has been investigated in several Phase II and III clinical trials, with results indicating a potential role in the management of EOC. This article provides an overview of pazopanib in the treatment of EOC. Keywords: pazopanib, antiangiogenic agents, ovarian carcinoma
Yadegarynia, Sina; Pham, Anh; Ng, Alex; Nguyen, Duong; Lialiutska, Tetiana; Bortolazzo, Anthony; Sivryuk, Valentin; Bremer, Martina; White, J Brandon
Flavonoids have been shown to be cytotoxic to cancer cells. However, the mechanism of cytotoxicity has not been clearly defined. It has previously been reported that HER2/ERBB2, the estrogen receptor, progesterone receptor, and p53 were required for flavonoid induced cytotoxicity in breast cancer cell lines. We have used a panel of breast cancer cell lines, known to contain as well as be deficient in these signaling pathways, to screen fourteen different flavonoids. Comparing the cytotoxicity for all flavonoids allows us to determine if a structure-functional relationship exists between cytotoxicity and flavonoid, and if a particular signaling pathway is required for cytotoxicity. We show that several flavonoids are cytotoxic to all cell lines including primary mammary epithelial cells tested. The cytotoxic flavonoids are also able to inhibit Mitochondrial Outer Membrane Permeability while at the same time stimulate ATP levels whereas the non-cytotoxic flavonoids are not able to do this. We also show that both cytotoxic and non-cytotoxic flavonoids can transverse the cell membrane to enter MDA-MB-231 cells at different levels. Finally, all flavonoids regardless of their cytotoxicity were able to induce some form of cell cycle arrest. We conclude that for flavonoids to be strongly cytotoxic, they must possess the 2,3-double bond in the C-ring and we believe the cytotoxicity occurs through mitochondrial poisoning in both cancer and normal cells.
D. Duijvesz (Diederick); K.E. Burnum-Johnson (Kristin); M.A. Gritsenko (Marina); A.M. Hoogland (Marije); M.S. Vredenbregt-van den Berg (Mirella); R. Willemsen (Rob); T.M. Luider (Theo); L. Paša-Tolić (Ljiljana); G.W. Jenster (Guido)
textabstractBackground: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, the complexity of body fluids often hampers biomarker discovery. An attractive alternative approach is the isolation of small vesicles, i.e. exosomes, ∼10
Kraeima, J.; Vliegen, I.; Siesling, S.; Klaase, J.; IJzerman, M.J.
Objectives Current international guidelines for breast cancer follow-up are not specific to individual risk of local regional recurrences. Instead, for personalised follow-up it is required to have more precise estimates of local regional recurrence probability as a function of time. The objective o
Macmahon, B.; Andersen, A.P.; Brown, J.; Cole, P.; Dewaard, V.; Kauraniemi, T.; Ravhinar, B.; Stormby, N.; Trichopoulos, D.; Westlund, K.
Urine estrogens of women in two age groups, 15 18 and 30-39, were measured in four northern European countries where breast cancer rates are high, two southern European countries where they are low, and in Finland, a northern country where incidence rates are comparable to those of the southern coun
Full Text Available Abstract Background New Zealand Māori have a poorer outcome from breast cancer than non-Māori, yet prognostic data are sparse. The objective of this study was to quantify levels of prognostic factors in a cohort of self-declared Māori and European breast cancer patients from Christchurch, New Zealand. Methods and Results Clinicopathological and survival data from 337 consecutive breast cancer patients (27 Māori, 310 European were evaluated. Fewer tumours were high grade in Māori women than European women (p = 0.027. No significant ethnic differences were detected for node status, tumour type, tumour size, human epidermal growth factor receptor, oestrogen and progesterone receptor (ER/PR status, or survival. In addition, tumour and serum samples from a sub-cohort of 14 Māori matched to 14 NZ European patients were analyzed by immunohistochemistry and enzyme linked immunosorbent assay for molecular prognostic factors. Significant correlations were detected between increased grade and increased levels of hypoxia inducible factor-1 (HIF-1α, glucose transporter-1 (GLUT-1, microvessel density (MVD and cytokeratins CK5/6 (p Conclusions In this Christchurch cohort of breast cancer patients, Māori women were no more likely than European women to have pathological or molecular factors predictive of poor prognosis. These data contrast with data from the North Island NZ, and suggest potential regional differences.
Beck, Hans Christian; Petersen, Jørgen; Nielsen, Søren Jensby;
in the human colon cancer cell line HCT116. Protein extracts from untreated HCT116 cells, and cells grown for 24 h in the presence of 1 and 10 muM belinostat were analysed by 2-D gel electrophoresis. Proteins were visualized by colloidal Coomassie blue staining and quantitative analysis of gel images revealed...
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Full Text Available Abstract Background Circulating tumor cells (CTCs have been associated with prognosis especially in breast cancer and have been proposed as a liquid biopsy for repeated follow up examinations. Molecular characterization of CTCs is difficult to address since they are very rare and the amount of available sample is very limited. Methods We quantified by RT-qPCR CK-19, MAGE-A3, HER-2, TWIST1, hTERT α+β+, and mammaglobin gene transcripts in immunomagnetically positively selected CTCs from 92 breast cancer patients, and 28 healthy individuals. We also compared our results with the CellSearch system in 33 of these patients with early breast cancer. Results RT-qPCR is highly sensitive and specific and can detect the expression of each individual gene at the one cell level. None of the genes tested was detected in the group of healthy donors. In 66 operable breast cancer patients, CK-19 was detected in 42.4%, HER-2 in 13.6%, MAGE-A3 in 21.2%, hMAM in 13.6%, TWIST-1 in 42.4%, and hTERT α+β+ in 10.2%. In 26 patients with verified metastasis, CK-19 was detected in 53.8%, HER-2 in 19.2%, MAGE-A3 in 15.4%, hMAM in 30.8%, TWIST-1 in 38.5% and hTERT α+β+in 19.2%. Our preliminary data on the comparison between RT-qPCR and CellSearch in 33 early breast cancer patients showed that RT-qPCR gives more positive results in respect to CellSearch. Conclusions Molecular characterization of CTCs has revealed a remarkable heterogeneity of gene expression between breast cancer patients. In a small percentage of patients, CTCs were positive for all six genes tested, while in some patients only one of these genes was expressed. The clinical significance of these findings in early breast cancer remains to be elucidated when the clinical outcome for these patients is known.
Dunstan, D. J.; Hodgson, D. J.
Many gardeners and horticulturalists seek non-chemical methods to control populations of snails. It has frequently been reported that snails that are marked and removed from a garden are later found in the garden again. This phenomenon is often cited as evidence for a homing instinct. We report a systematic study of the snail population in a small suburban garden, in which large numbers of snails were marked and removed over a period of about 6 months. While many returned, inferring a homing instinct from this evidence requires statistical modelling. Monte Carlo techniques demonstrate that movements of snails are better explained by drift under the influence of a homing instinct than by random diffusion. Maximum likelihood techniques infer the existence of two groups of snails in the garden: members of a larger population that show little affinity to the garden itself, and core members of a local garden population that regularly return to their home if removed. The data are strongly suggestive of a homing instinct, but also reveal that snail-throwing can work as a pest management strategy.
Wielscher, Matthias; Vierlinger, Klemens; Kegler, Ulrike; Ziesche, Rolf; Gsur, Andrea; Weinhäusel, Andreas
Disease-specific alterations of the cell-free DNA methylation status are frequently found in serum samples and are currently considered to be suitable biomarkers. Candidate markers were identified by bisulfite conversion-based genome-wide methylation screening of lung tissue from lung cancer, fibrotic ILD, and COPD. cfDNA from 400 μl serum (n = 204) served to test the diagnostic performance of these markers. Following methylation-sensitive restriction enzyme digestion and enrichment of methylated DNA via targeted amplification (multiplexed MSRE enrichment), a total of 96 markers were addressed by highly parallel qPCR. Lung cancer was efficiently separated from non-cancer and controls with a sensitivity of 87.8%, (95%CI: 0.67-0.97) and specificity 90.2%, (95%CI: 0.65-0.98). Cancer was distinguished from ILD with a specificity of 88%, (95%CI: 0.57-1), and COPD from cancer with a specificity of 88% (95%CI: 0.64-0.97). Separation of ILD from COPD and controls was possible with a sensitivity of 63.1% (95%CI: 0.4-0.78) and a specificity of 70% (95%CI: 0.54-0.81). The results were confirmed using an independent sample set (n = 46) by use of the four top markers discovered in the study (HOXD10, PAX9, PTPRN2, and STAG3) yielding an AUC of 0.85 (95%CI: 0.72-0.95). This technique was capable of distinguishing interrelated complex pulmonary diseases suggesting that multiplexed MSRE enrichment might be useful for simple and reliable diagnosis of diverse multifactorial disease states.
Full Text Available Cancer researchers have been looking for ways to harness the immune system and to reinstate immune surveillance, to kill cancer cells without collateral damage. Here we scan current approaches to targeting the immune system against cancer, and emphasize our own approach. We are using chemical vectors attached to a specific ligand, to introduce synthetic dsRNA, poly Inosine/Cytosine (polyIC, into tumors. The ligand binds to a receptor protein that is overexpressed on the surface of the tumor cells. Upon ligand binding, the receptor complex is internalized, introducing the polyIC into the cell. In this fashion a large amount of synthetic dsRNA can be internalized, leading to the activation of dsRNA binding proteins, such as dsRNA dependent protein kinase (PKR, Toll-3 receptor (TLR3, retinoic acid–inducible gene I (RIG-1 and melanoma differentiation–associated gene 5 (MDA5. The simultaneous activation of these signaling proteins leads to the rapid demise of the targeted cell and to cytokine secretion. The cytokines lead to a strong bystander effect and to the recruitment of immune cells that converge upon the targeted cells. The bystander effects lead to the destruction of neighboring tumor cells not targeted themselves by the vector. Normal cells, being more robust than tumor cells, survive. This strategy has several advantages: (1 Recruitment of the immune system is localized to the tumor. (2 The response is rapid, leading to fast tumor eradication. (3 The bystander effects lead to the eradication of tumor cells not harboring the target. (4 The multiplicity of pro-death signaling pathways elicited by PolyIC minimizes the likelihood of the emergence of resistance. In this chapter we focus on EGFR as the targeted receptor, which is overexpressed in many tumors. In principle, the strategy can be extended to other tumors that overexpress a protein that can be internalized by a ligand, which be a small molecule, a single chain antibody or an
Cancer researchers have been looking for ways to harness the immune system and to reinstate immune surveillance, to kill cancer cells without collateral damage. Here we scan current approaches to targeting the immune system against cancer, and emphasize our own approach. We are using chemical vectors attached to a specific ligand, to introduce synthetic dsRNA, polyinosine/cytosine (polyIC), into tumors. The ligand binds to a receptor protein that is overexpressed on the surface of the tumor cells. Upon ligand binding, the receptor complex is internalized, introducing the polyIC into the cell. In this fashion a large amount of synthetic dsRNA can be internalized, leading to the activation of dsRNA-binding proteins, such as dsRNA dependent protein kinase (PKR), Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-1), and melanoma differentiation-associated gene 5 (MDA5). The simultaneous activation of these signaling proteins leads to the rapid demise of the targeted cell and to cytokine secretion. The cytokines lead to a strong bystander effect and to the recruitment of immune cells that converge upon the targeted cells. The bystander effects lead to the destruction of neighboring tumor cells not targeted themselves by the vector. Normal cells, being more robust than tumor cells, survive. This strategy has several advantages: (1) recruitment of the immune system is localized to the tumor. (2) The response is rapid, leading to fast tumor eradication. (3) The bystander effects lead to the eradication of tumor cells not harboring the target. (4) The multiplicity of pro-death signaling pathways elicited by PolyIC minimizes the likelihood of the emergence of resistance. In this chapter we focus on EGFR as the targeted receptor, which is overexpressed in many tumors. In principle, the strategy can be extended to other tumors that overexpress a protein that can be internalized by a ligand, which can be a small molecule, a single chain antibody, or an affibody.
Halvorsen, Ann Rita; Helland, Åslaug; Gromov, Pavel
and to elucidate the cross-talk that exists among cells in a tumor microenvironment. Matched tumor interstitial fluid samples (TIF, n = 60), normal interstitial fluid samples (NIF, n = 51), corresponding tumor tissue specimens (n = 54), and serum samples (n = 27) were collected from patients with breast cancer......, and detectable microRNAs were analyzed and compared. In addition, serum data from 32 patients with breast cancer and 22 healthy controls were obtained for a validation study. To identify potential serum biomarkers of breast cancer, first the microRNA profiles of TIF and NIF samples were compared. A total of 266...
Halvorsen, Ann Rita; Helland, Åslaug; Gromov, Pavel;
and to elucidate the cross-talk that exists among cells in a tumor microenvironment. Matched tumor interstitial fluid samples (TIF, n = 60), normal interstitial fluid samples (NIF, n = 51), corresponding tumor tissue specimens (n = 54), and serum samples (n = 27) were collected from patients with breast cancer......, and detectable microRNAs were analyzed and compared. In addition, serum data from 32 patients with breast cancer and 22 healthy controls were obtained for a validation study. To identify potential serum biomarkers of breast cancer, first the microRNA profiles of TIF and NIF samples were compared. A total of 266...
Lu, Jun; Zhang, Xiaoli; Shen, Tingting; Ma, Chao; Wu, Jun; Kong, Hualei; Tian, Jing; Shao, Zhifeng; Zhao, Xiaodong; Xu, Ling
Traditional Chinese medicine Jinfukang (JFK) has been clinically used for treating lung cancer. To examine whether epigenetic modifications are involved in its anticancer activity, we performed a global profiling analysis of H3K4Me3, an epigenomic marker associated with active gene expression, in JFK-treated lung cancer cells. We identified 11,670 genes with significantly altered status of H3K4Me3 modification following JFK treatment (P JFK. Collectively, these findings provide the first evidence that the anticancer activity of JFK involves modulation of histone modification at many cancer-related gene loci.
Olsen, Dorte Aa; Ostergaard, Birthe; Bokmand, Susanne;
and the proteins extracted. The tissue and serum concentrations of HER1-4 were determined quantitatively using a commercially available enzyme linked immunosorbent assay (ELISA) method. Results: HER1 was down regulated in cancer tissue when compared to autologous reference tissue (p=8x10(-6)), while HER2 (p...-4 system. We have mapped the protein concentrations of HER1-4 in breast cancer tissue, autologous reference tissue, normal breast tissue and serum samples, to see whether non-cancer cells from these patients express a protein profile indicating general activation. Methods: Tissue samples from malignant...
王毅欣; 沈洁; 徐燕
Objective To further explore the status and influencing factors of palliative home care service for advanced cancer patients,and thus to provide guidance for the development of palliative home care. Methods Phenomenology method was used in the study. Ten palliative home care providers in five community health centers were interviewed by semi-structure interviews. Results The current palliative home care services for advanced cancer patients provided by community health centers focused on regular follow-up,hospital bed at home and temporary home visit,which still need to be broadened and improved The influencing factors of developing community-based palliative home care were factors in the aspects of policy,service provider and receiver. Conclusion The development of palliative home care service is in need of policy support,good community health services and public's trust and understanding.%目的 深入了解晚期癌症患者居家姑息照护服务现状及其影响因素,为规范发展居家姑息照护服务提供参考.方法 采用现象学研究方法,对10名社区卫生服务中心的医护人员进行非结构访谈,用现象学分析法进行资料分析.结果:社区卫生服务中心为晚期癌症患者开展定期随访、家庭病床、临时出诊等居家姑息服护服务,有待进一步拓展与完善;归纳影响居家姑息照护服务开展的3个主题为政策环境因素、服务供方因素、服务需方因素.结论:居家姑息照护服务的开展需要政策支持,完善杜区卫生服务和提高公众信任与理解.
Wanling Yang; Dingge Ying; Yu-Lung Lau
procedures may allow detection of many expres-sion features for less abundant gene variants. With the reduction of sequencing cost and the emerging of new generation sequencing technology, in-depth sequencing of cDNA pools or libraries may represent a better and powerful tool in gene expression profiling and cancer biomarker detection. We also propose using sequence-specific subtraction to remove hundreds of the most abundant housekeeping genes to in-crease sequencing depth without affecting relative expression ratio of other genes, as transcripts from as few as 300 most abundantly expressed genes constitute about 20% of the total transcriptome. In-depth sequencing also represents a unique ad-vantage of detecting unknown forms of transcripts, such as alternative splicing variants, fusion genes, and regulatory RNAs, as well as detecting mutations and polymorphisms that may play important roles in disease pathogenesis.
@@ Television audiences around the country were shocked on November 21,2009, when national broadcaster China Central Television showed clips of two families violently fighting lawenforcement officials who were evicting them from their homes. The first incident being broadcast happened in June 2008, when Pan Rong and her husband stood on the roof of their four-story house to confront a demolition crew that consisted of police officers, firefighters and a bulldozer. Their family home stood in the way of a Shanghai Hongqiao Airport expansion project. Pan shouted into a loudspeaker,"If you don't have a court verdict, you are violating our property rights."
FU Zhong-yan; HAN Jin-xiang; HUANG Hai-yan
Background The treatment of patients with small cell lung cancer (SCLC) is based on chemotherapy. However, the treatment is limited by the development of drug resistance. Emodin has been shown to exhibit an anti-cancer effect. But the molecular mechanism remains unclear. This study was conducted to investigate the effect of emodin on the gene expression profile changes in SCLC NCI-H446 cells.Methods NCI-H446 cells were treated with emodin and cell viability was determined by MTT assay. Cell apoptosis was determined by both flow cytometry and caspase-3 activity assay. The effect of emodin on the gene expression profile of NCI-H446 cells was analyzed using cDNA microarray. Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to validate the microarray results.Results Emodin suppressed viability, induced apoptosis and changed cell cycle of NCI-H446 cells. Among the 1262 genes, 10 genes were up-regulated and 8 genes were down-regulated more than 2 folds in NCI-H446 cells when compared with the control cells after treatment with emodin for 12 hours, while 12 genes were up-regulated and 24 genes were down-regulated after treatment with emodin for 24 hours. These genes were involved in metabolism, signal transduction, transcription regulation, cytoskeleton organization, immune response, transport, protein synthesis, cell cycle control, cell adhesion and RNA processing. The RT-PCR results were consistent with those obtained by the microarray.Conclusions Emodin affects the expression of genes involved in various cellular functions and plays important roles in cell apoptosis, tumor metastasis and chemotherapy-resistance, which suggests emodin might become an effective chemopreventive or chemotherapeutic agent for SCLC.
Luis I, Seah D, Olson EM, Wagle N, Metzger-Filho O, Sohl J, Litsas G, Burstein HJ, Krop IE, Winer EP, Lin NU. Clinicopathological features among...33. Epub 2013 Apr 15. (4) Abstracts: 1. Vaz- Luis I, Seah D, Olson E, Metzger O, Wagle N, Sohl J, Litsas G, Burstein H, Krop I, Winer E, and Lin...simultaneously. 104th American Association for Cancer Research Annual Meeting, Washington, DC, April 6-10, 2013. 5. Rodon J, Juric D, Gonzalez
Nursing home checklist Name of nursing home: ____________________________________________________ Address: ________________________________________________________________ Phone number: __________________________________________________________ Date of visit: _____________________________________________________________ Basic information Yes No Notes Is the nursing home Medicare certified? Is the nursing ...
Full Text Available Objective: Colorectal cancer (CRC is one of the most common and aggressive cancers worldwide. The majority of CRC cases are sporadic that caused by somatic mutations. The Adenomatous Polyposis Coli (APC; OMIM 611731 is a tumor suppressor gene of Wnt pathway and is frequently mutated in CRC cases. This study was designed to investigate the spectrum of APC gene mutations in Iranian patients with sporadic colorectal cancer. Materials and Methods: In this descriptive study, Tumor and normal tissue samples were obtained from thirty randomly selected and unrelated sporadic CRC patients. We examined the hotspot region of the APC gene in all patients. Our mutation detection method was direct DNA sequencing. Results: We found a total of 8 different APC mutations, including two nonsense mutations (c.4099C>T and c.4348C>T, two missense mutations (c.3236C>G and c.3527C>T and four frame shift mutations (c.2804dupA, c.4317delT, c.4464_4471delATTACATT and c.4468_4469dupCA. The c.3236C>G and c.4468_4469dupCA are novel mutations. The overall frequency of APC mutation was 26.7% (8 of 30 patients. Conclusion: This mutation rate is lower in comparison with previous studies from other countries. The findings of present study demonstrate a different APC mutation spectrum in CRC patients of Iranian origin compared with other populations.
Gang-Qiang Li; Hong-Fu Zhang
AIM: To investigate the expression of tumor suppressor gene p27 and spindle checkpoint gene Mad2 and to demonstrate their expression difference in colorectal cancerand normal mucosa and to evaluate its clinical significance.METHODS: Immunohistochemical staining was used for detection of expression of Mad2 and p27in colorectal cancer and its corresponding normal mucosa.RESULTS: Mad2 was significantly overexpressed in colorectal cancer compared with corresponding normal mucosa (P＜0.01, χ2= 7.5), and it was related to the differentiation of adenocarcinoma, lymph node metastasis and survival period after excision (P＜0.05, χ2 = 7.72, χ2 = 4.302,χ2= 6.234). The rate of p27 positive expression in adenocarcinomas and normal mucosa was 40% and 80%respectively. There was a significant difference in p27expression between adenocarcinomas and normal mucosa (P＜0.001, χ2 = 13.333), which was related to the differentiation degree of adenoca rcinoma and lymph node metastasis (P＜0.05, χ2 = 8.901 χ2 = 4). The positive expression of p27was not correlated with survival period after excision.CONCLUSION: Defect of spindle checkpoint gene Mad2and mutation of p27 gene are involved mainly in colorectal carcinogenesis and associated with prognosis of colorectal cancer.
Full Text Available Introduction: It would be useful to understand which populations are not reached by home-based HIV-1 testing and counselling (HTC to improve strategies aimed at linking these individuals to care and reducing rates of onward HIV transmission. Methods: We present the results of a baseline home-based HTC (HBHTC campaign aimed at counselling and testing residents aged 16 to 64 for HIV in the north-eastern sector of Mochudi, a community in Botswana with about 44,000 inhabitants. Collected data were compared with population references for Botswana, the United Nations (UN estimates based on the National Census data and the Botswana AIDS Impact Survey IV (BAIS-IV. Analyzed data and references were stratified by age and gender. Results: A total of 6238 age-eligible residents were tested for HIV-1; 1247 (20.0%; 95% CI 19.0 to 21.0% were found to be HIV positive (23.7% of women vs. 13.4% of men. HIV-1 prevalence peaked at 44% in 35- to 39-year-old women and 32% in 40- to 44-year-old men. A lower HIV prevalence rate, 10.9% (95% CI 9.5 to 12.5%, was found among individuals tested for the first time. A significant gender gap was evident in all analyzed subsets. The existing HIV transmission network was analyzed by combining phylogenetic mapping and household structure. Between 62.4 and 71.8% of all HIV-positive individuals had detectable virus. When compared with the UN and BAIS-IV estimates, the proportion of men missed by the testing campaign (48.5%; 95% CI 47.0 to 50.0% was significantly higher than the proportion of missed women (14.2%; 95% CI 13.2 to 15.3%; p<0.0001. The estimated proportion of missed men peaked at about 60% in the age group 30 to 39 years old. The proportions of missed women were substantially smaller, at approximately 28% within the age groups 30 to 34 and 45 to 49 years old. Conclusions: The HBHTC campaign seems to be an efficient tool for reaching individuals who have never been tested previously in southern African communities
Chang, Kah Hoong
Abstract Background Advances in high-throughput technologies and bioinformatics have transformed gene expression profiling methodologies. The results of microarray experiments are often validated using reverse transcription quantitative PCR (RT-qPCR), which is the most sensitive and reproducible method to quantify gene expression. Appropriate normalisation of RT-qPCR data using stably expressed reference genes is critical to ensure accurate and reliable results. Mi(cro)RNA expression profiles have been shown to be more accurate in disease classification than mRNA expression profiles. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in miRNA RT-qPCR studies. Methods We adopt and report a systematic approach to identify the most stable reference genes for miRNA expression studies by RT-qPCR in colorectal cancer (CRC). High-throughput miRNA profiling was performed on ten pairs of CRC and normal tissues. By using the mean expression value of all expressed miRNAs, we identified the most stable candidate reference genes for subsequent validation. As such the stability of a panel of miRNAs was examined on 35 tumour and 39 normal tissues. The effects of normalisers on the relative quantity of established oncogenic (miR-21 and miR-31) and tumour suppressor (miR-143 and miR-145) target miRNAs were assessed. Results In the array experiment, miR-26a, miR-345, miR-425 and miR-454 were identified as having expression profiles closest to the global mean. From a panel of six miRNAs (let-7a, miR-16, miR-26a, miR-345, miR-425 and miR-454) and two small nucleolar RNA genes (RNU48 and Z30), miR-16 and miR-345 were identified as the most stably expressed reference genes. The combined use of miR-16 and miR-345 to normalise expression data enabled detection of a significant dysregulation of all four target miRNAs between tumour and normal colorectal tissue. Conclusions Our study demonstrates that the top six most
Chang, Kah Hoong
BACKGROUND: Advances in high-throughput technologies and bioinformatics have transformed gene expression profiling methodologies. The results of microarray experiments are often validated using reverse transcription quantitative PCR (RT-qPCR), which is the most sensitive and reproducible method to quantify gene expression. Appropriate normalisation of RT-qPCR data using stably expressed reference genes is critical to ensure accurate and reliable results. Mi(cro)RNA expression profiles have been shown to be more accurate in disease classification than mRNA expression profiles. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in miRNA RT-qPCR studies. METHODS: We adopt and report a systematic approach to identify the most stable reference genes for miRNA expression studies by RT-qPCR in colorectal cancer (CRC). High-throughput miRNA profiling was performed on ten pairs of CRC and normal tissues. By using the mean expression value of all expressed miRNAs, we identified the most stable candidate reference genes for subsequent validation. As such the stability of a panel of miRNAs was examined on 35 tumour and 39 normal tissues. The effects of normalisers on the relative quantity of established oncogenic (miR-21 and miR-31) and tumour suppressor (miR-143 and miR-145) target miRNAs were assessed. RESULTS: In the array experiment, miR-26a, miR-345, miR-425 and miR-454 were identified as having expression profiles closest to the global mean. From a panel of six miRNAs (let-7a, miR-16, miR-26a, miR-345, miR-425 and miR-454) and two small nucleolar RNA genes (RNU48 and Z30), miR-16 and miR-345 were identified as the most stably expressed reference genes. The combined use of miR-16 and miR-345 to normalise expression data enabled detection of a significant dysregulation of all four target miRNAs between tumour and normal colorectal tissue. CONCLUSIONS: Our study demonstrates that the top six most
Aneta A Koronowicz
Full Text Available Although iodization of salt is the most common method used to obtain iodine-enriched food, iodine deficiency disorders are still a global health problem and profoundly affect the quality of human life. Iodine is required for the synthesis of thyroid hormones, which are crucial regulators of human metabolism, cell growth, proliferation, apoptosis and have been reported to be involved in carcinogenesis. In this study, for the first time, we evaluated the effect of iodine-biofortified lettuce on transcriptomic profile of Caco-2 cancer cell line by applying the Whole Human Genome Microarray assay. We showed 1326 differentially expressed Caco-2 transcripts after treatment with iodine-biofortified (BFL and non-fortified (NFL lettuce extracts. We analysed pathways, molecular functions, biological processes and protein classes based on comparison between BFL and NFL specific genes. Iodine, which was expected to act as a free ion (KI-NFL or at least in part to be incorporated into lettuce macromolecules (BFL, differently regulated pathways of numerous transcription factors leading to different cellular effects. In this study we showed the inhibition of Caco-2 cells proliferation after treatment with BFL, but not potassium iodide (KI, and BFL-mediated induction of mitochondrial apoptosis and/or cell differentiation. Our results showed that iodine-biofortified plants can be effectively used by cells as an alternative source of this trace element. Moreover, the observed differences in action of both iodine sources may suggest a potential of BFL in cancer treatment.
Liu, Yong-Qi; Li, Yi; Qin, Jie; Wang, Qian; She, Ya-Li; Luo, Ya-Li; He, Jian-Xin; Li, Jing-Ya; Xie, Xiao-Dong
Matrine, a main active component extracted from dry roots of Sophora flavecens , has been reported to exert antitumor effects on A549 human non-small lung cancer cells, but its mechanisms of action remain unclear. To determine effects of matrine on proliferation of A549 cells and assess possible mechanisms, MTT assays were employed to detect cytotoxicity, along with o flow cytometric analysis of DNA content of nuclei of cells following staining with propidium iodide to analyze cell cycle distribution. Western blotting was performed to determined expression levels of Bax, Bcl-2, VEGF and HDAC1, while a microarray was used to assessed changes of miRNA profiles. In the MTT assay, matrine suppressed growth of human lung cancer cell A549 in a dose- and time- dependent manner at doses of 0.25-2.5 mg/ml for 24h, 48h or 72h. Matrine induced cell cycle arrest in G0/G1 phase and decreased the G2/M phase, while down-regulating the expression of Bcl2 protein, leading to a reduction in the Bcl-2/Bax ratio. In addition, matrine down regulated the expression level of VEGF and HDAC1 of A549 cells. Microarray analysis demonstrated that matrine altered the expression level of miRNAs compared with untreated control A549 cells. In conclusion, matrine could inhibit proliferation of A549 cells, providing useful information for understanding anticancer mechanisms.
Koronowicz, Aneta A; Kopeć, Aneta; Master, Adam; Smoleń, Sylwester; Piątkowska, Ewa; Bieżanowska-Kopeć, Renata; Ledwożyw-Smoleń, Iwona; Skoczylas, Łukasz; Rakoczy, Roksana; Leszczyńska, Teresa; Kapusta-Duch, Joanna; Pysz, Mirosław
Although iodization of salt is the most common method used to obtain iodine-enriched food, iodine deficiency disorders are still a global health problem and profoundly affect the quality of human life. Iodine is required for the synthesis of thyroid hormones, which are crucial regulators of human metabolism, cell growth, proliferation, apoptosis and have been reported to be involved in carcinogenesis. In this study, for the first time, we evaluated the effect of iodine-biofortified lettuce on transcriptomic profile of Caco-2 cancer cell line by applying the Whole Human Genome Microarray assay. We showed 1326 differentially expressed Caco-2 transcripts after treatment with iodine-biofortified (BFL) and non-fortified (NFL) lettuce extracts. We analysed pathways, molecular functions, biological processes and protein classes based on comparison between BFL and NFL specific genes. Iodine, which was expected to act as a free ion (KI-NFL) or at least in part to be incorporated into lettuce macromolecules (BFL), differently regulated pathways of numerous transcription factors leading to different cellular effects. In this study we showed the inhibition of Caco-2 cells proliferation after treatment with BFL, but not potassium iodide (KI), and BFL-mediated induction of mitochondrial apoptosis and/or cell differentiation. Our results showed that iodine-biofortified plants can be effectively used by cells as an alternative source of this trace element. Moreover, the observed differences in action of both iodine sources may suggest a potential of BFL in cancer treatment.
Full Text Available Epithelial ovarian cancer consists of multiple histotypes differing in etiology and clinical course. The most prevalent histotype is high-grade serous ovarian cancer (HGSOC, which often presents at an advanced stage frequently accompanied with high-volume ascites. While some studies suggest that ascites is associated with poor clinical outcome, most reports have not differentiated between histological subtypes or tumor grade. We compared genome-wide gene expression profiles from a discovery cohort of ten patients diagnosed with stages III-IV HGSOC with high-volume ascites and nine patients with low-volume ascites. An upregulation of immune response genes was detected in tumors from patients presenting with low-volume ascites relative to those with high-volume ascites. Immunohistochemical studies performed on tissue microarrays confirmed higher expression of proteins encoded by immune response genes and increased tumorinfiltrating cells in tumors associated with low-volume ascites. Comparison of 149 advanced-stage HGSOC cases with differential ascites volume at time of primary surgery indicated low-volume ascites correlated with better surgical outcome and longer overall survival. These findings suggest that advanced stage HGSOC presenting with low-volume ascites reflects a unique subgroup of HGSOC, which is associated with upregulation of immune related genes, more abundant tumor infiltrating cells and better clinical outcomes.
Abramson, Vandana G; Cooper Lloyd, M; Ballinger, Tarah; Sanders, Melinda E; Du, Liping; Lai, Darson; Su, Zengliu; Mayer, Ingrid; Levy, Mia; LaFrance, Delecia R; Vnencak-Jones, Cindy L; Shyr, Yu; Dahlman, Kimberly B; Pao, William; Arteaga, Carlos L
Mutations in the PIK3CA gene are common in breast cancer and represent a clinically useful therapeutic target. Several larger, population-based studies have shown a positive prognostic significance associated with these mutations. This study aims to further identify characteristics of patients harboring PIK3CA mutations while evaluating the clinical impact of genomic testing for these mutations. Tumors from 312 patients at Vanderbilt-Ingram Cancer Center were analyzed for PIK3CA mutations using a multiplex screening assay (SNaPshot). Mutation rates, receptor status, histopathologic characteristics, and time to recurrence were assessed. The number of patients participating in clinical trials, specifically trials relating to the PIK3CA mutation, was examined. Statistically significant differences between wild-type and mutated tumors were determined using the Wilcoxon, Pearson, and Fischer exact tests. The PIK3CA mutation was found in 25 % of tumors tested. Patients with PIK3CA mutations were significantly more likely to express hormone receptors, be of lower combined histological grade, and have a reduced time to recurrence. Patients found to have a PIK3CA mutation were significantly more likely to enter a PIK3CA-specific clinical trial. In addition to confirming previously established positive prognostic characteristics of tumors harboring PIK3CA mutations, this study demonstrates the feasibility and utility of mutation profiling in a clinical setting. PIK3CA mutation testing impacted treatment and resulted in more patients entering mutation-specific clinical trials.
Janssens, G.O.R.J.; Terhaard, C.H.J.; Doornaert, P.A.; Bijl, H.P.; Ende, P. van den; Chin, A.; Pop, L.A.M.; Kaanders, J.H.A.M.
PURPOSE: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. METHODS AND MATERIALS: From April 2001 to February 2008, 345 patients with
Janssens, Geert O.; Terhaard, Chris H.; Doornaert, Patricia A.; Bijl, Hendrik P.; van den Ende, Piet; Chin, Alim; Pop, Lucas A.; Kaanders, Johannes H.
Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with
Full Text Available Abstract Smart homes have been viewed with increasing interest by both home owners and the research community in the past few years. One reason for this development is that the use of modern automation technology in the home or building promises considerable savings of energy, therefore, simultaneously reducing the operational costs of the building over its whole lifecycle. However, the full potential of smart homes still lies fallow, due to the complexity and diversity of the systems, badly engineered and configured installations, as well as the frequent problem of suboptimal control strategies. Summarized, these problems converge to two undesirable conditions in the "not-so-smart" home: energy consumption is still higher than actually necessary and users are unable to yield full comfort in their automated homes. This work puts its focus on alleviating the current problems by proposing a comprehensive system concept, that shall ensure that smart homes can keep their promise in the future. The system operates on an extensive knowledge base that stores all information needed to fulfill the goals of energy efficiency and user comfort. Its intelligence is implemented as and within a multiagent system that also caters for the system's openness to the outside world. As a first evaluation, a profile-based control strategy for thermal comfort is developed and verified by means of simulation.
Maja M. Kosanovic
Full Text Available Prostate specific antigen (PSA exhibits pronounced heterogeneity in both primary structure and glycan composition, resulting in the existence of different molecular forms. Investigation of PSA structure is a demanding task facing limitations due to inadequate sensitivity of analytical techniques and low concentrations of the different forms. This study aimed to profile free PSA (fPSA, especially lower molecular mass species lacking detailed classification, in normal seminal plasma and in sera from subjects with benign hyperplasia (BPH or cancer of the prostate (PCa as samples of known clinical relevance. fPSA forms were separated from complex proteomes on chips with immobilized anti-fPSA antibody followed by detection using surface-enhanced laser desorption/ionization time of flight mass spectrometry. At least 39 fPSA-immunoreactive species, ranging from 3–29 kDa were detected in seminal plasma. General fPSA profiles in seminal plasma and sera were similar, but differed in the abundance and presence of particular peaks/clusters of the lower molecular mass species. No striking difference in fPSA forms was observed between BPH and PCa samples, but some distinct peaks varied in intensity and frequency within or between groups. Obtained data verify fPSA heterogeneity that might be important for better exploration of all their molecular and marker potentials.
Full Text Available Motivation: Identifying genes with bimodal expression patterns from large-scale expression profiling data is an important analytical task. Model-based clustering is popular for this purpose. That technique commonly uses the Bayesian information criterion (BIC for model selection. In practice, however, BIC appears to be overly sensitive and may lead to the identification of bimodally expressed genes that are unreliable or not clinically useful. We propose using a novel criterion, the bimodality index, not only to identify but also to rank meaningful and reliable bimodal patterns. The bimodality index can be computed using either a mixture model-based algorithm or Markov chain Monte Carlo techniques.Results: We carried out simulation studies and applied the method to real data from a cancer gene expression profiling study. Our findings suggest that BIC behaves like a lax cutoff based on the bimodality index, and that the bimodality index provides an objective measure to identify and rank meaningful and reliable bimodal patterns from large-scale gene expression datasets. R code to compute the bimodality index is included in the ClassDiscovery package of the Object-Oriented Microarray and Proteomic Analysis (OOMPA suite available at the web site http://bioinformatics.mdanderson.org/Software/OOMPA.
... Associated Lung Ovarian Prostate Skin Uterine Cancer Home Breast Cancer Rates by State Language: English Español (Spanish) Recommend ... from breast cancer each year. Rates of Getting Breast Cancer by State The number of people who get ...
A much-anticipated law protecting homeowners’ rights is on the horizon Television audiences around the country were shocked on November 21,2009,when national broadcaster China Central Television showed clips of two families violently fighting lawenforcement officials who were evicting them from their homes.
Agergaard, Jytte; Brøgger, Ditte
flows. By focusing on these educational migrants, this paper explores how they connect to their rural homes. Guided by a critical reading of the migration-development scholarship, the paper examines how migrants and their relatives make sense of educational migrants’ remitting and returning practices...... and partake in important social remittance practices that represent a vision for impacting local development...
In this paper I briefly discuss the importance of home automation system. Going in to the details I briefly present a real time designed and implemented software and hardware oriented house automation research project, capable of automating house's electricity and providing a security system to detect the presence of unexpected behavior.
Vecchio, Lorella; Seke Etet, Paul Faustin; Kipanyula, Maulilio John; Krampera, Mauro; Nwabo Kamdje, Armel Hervé
Epigenetic alterations represent a key cancer hallmark, even in hematologic malignancies (HMs) or blood cancers, whose clinical features display a high inter-individual variability. Evidence accumulated in recent years indicates that inactivating DNA hypermethylation preferentially targets the subset of polycomb group (PcG) genes that are regulators of developmental processes. Conversely, activating DNA hypomethylation targets oncogenic signaling pathway genes, but outcomes of both events lead in the overexpression of oncogenic signaling pathways that contribute to the stem-like state of cancer cells. On the basis of recent evidence from population-based, clinical and experimental studies, we hypothesize that factors associated with risk for developing a HM, such as metabolic syndrome and chronic inflammation, trigger epigenetic mechanisms to increase the transcriptional expression of oncogenes and activate oncogenic signaling pathways. Among others, signaling pathways associated with such risk factors include pro-inflammatory nuclear factor κB (NF-κB), and mitogenic, growth, and survival Janus kinase (JAK) intracellular non-receptor tyrosine kinase-triggered pathways, which include signaling pathways such as transducer and activator of transcription (STAT), Ras GTPases/mitogen-activated protein kinases (MAPKs)/extracellular signal-related kinases (ERKs), phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR), and β-catenin pathways. Recent findings on epigenetic mechanisms at work in HMs and their importance in the etiology and pathogenesis of these diseases are herein summarized and discussed. Furthermore, the role of epigenetic processes in the determination of biological identity, the consequences for interindividual variability in disease clinical profile, and the potential of epigenetic drugs in HMs are also considered.
Kailavasan, Mithun; Rehman, Ishtiaq; Reynolds, Steven; Bucur, Adriana; Tozer, Gillian; Paley, Martyn
The aim of this study was to evaluate the metabolic profile of human prostate cancer cells that have different metastatic potential and to determine their response to dichloroacetate (DCA) using NMR technology. Two isogenic human prostate cancer cell lines, differing in their metastatic potential [LNCaP (poorly metastatic) and LNCaP-LN3 (highly metastatic)], were studied. Metabolite ratios from NMR spectral integrals acquired at a field strength of 9.4 T using a 5-mm broadband probe with an NMR-compatible bioreactor were compared in the presence and absence of the pyruvate dehydrogenase kinase inhibitor DCA. Lactate dehydrogenase (LDH) isoenzymes were assessed by zymography. Following the treatment of cells with 50 mm DCA, there was a significant reduction in the lactate/choline, lactate/creatine, lactate/alanine and the combined lactate/(choline + creatine + alanine) ratios in LNCaP-LN3 cells relative to LNCaP cells. No significant changes in metabolite ratios were found in LNCaP cells following DCA treatment. As expected, LDH zymography assays showed an absence of the LDH-B subunit in LNCaP-LN3 cells, whereas both LDH-A and LDH-B subunits were present in LNCaP cells. DCA was shown to significantly modify the metabolite ratios in highly metastatic LNCaP-LN3 cells, but not in poorly metastatic LNCaP cells. This effect was probably related to the absence of the LDH-B subunit in LNCaP-LN3 cells, and could have a bearing on cancer treatment with DCA and related compounds.
Full Text Available Background: Different molecular classes of breast cancer (BRCA correlate with prognosis and response to therapy. Triple-negative breast cancer (TNBC is a newer concept and very limited studies were carried out in India. The aim of this study was to profile the molecular types with a particular emphasis on TNBCs. Materials and Methods: Prospectively evaluated descriptive study for 2 years from June 2014 to March 2016, was carried out in the Department of Pathology and Surgery in a tertiary care institute. Cases included were of invasive breast carcinoma in females, confirmed by histopathology. Ethical clearance was received. Data were analyzed using Statistical SAS software. Results: A total of 123 cases of invasive BRCA were studied and mean age was 44.64 years. The peak age group was 36–45 years (43.9%. Tumor sizes ≥2 cm was 30%, between 2 and 5 cm was 50.40%, over 5 cm was 19.51%. Invasive duct carcinoma was 82.11% and invasive lobular carcinoma 8.13%. Only 21% of subjects presented as early breast carcinoma. Cases of 1–3 nodes were 22.8%, 4–5 nodes 21.1%, more than five nodes were 34%. Histologic Grade 3 was 50.4%, Grade 2 was 41%, and Grade 1 was only 8.1. The American Joint Committee on Cancer, Stage 1 (17.9% in Stage 2 (29.3% Stage 3 was 46.3%, Stage 4 was 6.5%. Estrogen receptor was in 40.62%, progesterone receptor 35.77%, Her2/Neu 18.69% luminal A (19.51%, luminal B (21.13%, Her2/Neu type (17.88%, and triple negatives (38.21. Conclusion: The present study showed significantly higher TNBC with poor prognostic factors in younger women in a background of peculiar ethic spectrum in this geographical region.
Shineng Zhang; Haijun Zuo; Zhong Yu; Fengting Huang; Wa Zhong
Objective:To analyze initially the differences of miRNAs expression profiles in human pancreatic cencer cell lines by microarray technique.Methods:A total of 743 probes were designed according to lhe known miRNAs sequences of human,mice,and rats.miRNAs microarray was manufactured and its credibility was verified.Total RNAs were extracted and miRNAs were separated from human pancreatic cancer cell lines(SW1990,Capan-2.BxPC-3,Aspc-1,and Panc 1)and immortal human pancreatic duct epithelial cell line H6C7.They were labeled with T4 RNA ligase.then were hybridized with microarray.Through array scan and analysis,miRNAs expression profiles in pancreatic cancer were obtained.The results were verified by Northern blotting and RT-PCR.Results:A totsl of 63 miRNAs related to pancreatic cancer were found to be differentially expressed in 5 pancreatic cancer cell lines.including 25 down-regulated and 38 up-regulated miRNAs.Expres- sions of mir-21 and let-7 were also confirmed.Conclusion:The results suggested that miRNAs expression profiles could befound in pancreatic cancer cells.
... and vegetables. There is no standard or routine screening test for stomach cancer. Standard treatments for stomach cancer include surgery , ... NCI Stomach (Gastric) Cancer Home Page Information about stomach ... causes, screening, clinical trials, research and statistics from the National ...
Full Text Available BACKGROUND: The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. OBJECTIVE: To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. METHODS: To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. RESULTS AND CONCLUSIONS: We created a manually annotated database (Targeted Therapy Database, TTD where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method
Beck, Hans Christian; Petersen, Jørgen; Nielsen, Søren Jensby
in the human colon cancer cell line HCT116. Protein extracts from untreated HCT116 cells, and cells grown for 24 h in the presence of 1 and 10 muM belinostat were analysed by 2-D gel electrophoresis. Proteins were visualized by colloidal Coomassie blue staining and quantitative analysis of gel images revealed......, and HSP90B that all were related to the proto-oncogene proteins p53, Myc, activator protein 1, and c-fos protein. The modulation of these proteins is consistent with the observations that belinostat is able to inhibit clonogenic cell growth of HCT116 cells and the biological role of these proteins...
Association for Cancer research; April 5- 9 2014; San Diego, CA. Abstract #2352. • Ooi AT, Gower AC, Zhang K, Vick J, Hong LS, Fishbein M, Nagao B, Wallace...Hong LS, Pagano PC, Liclican EL, Krysan K, Larsen JE, Fishbein MC, Minna JD, Lenburg ME, Spira A, Dubinett SM. The impact of e-cigarettes exposure on...Krysan K, Walser T, Seki A, Tran L, Spira A, Fishbein M, Dubinett S. The mutational landscape of pulmonary premalignancy in the context of lung
Full Text Available A CpG island methylator phenotype (CIMP is displayed by a distinct subset of colorectal cancers with a high frequency of DNA hypermethylation in a specific group of CpG islands. Recent studies have shown that an activating mutation of BRAF (BRAF(V600E is tightly associated with CIMP, raising the question of whether BRAF(V600E plays a causal role in the development of CIMP or whether CIMP provides a favorable environment for the acquisition of BRAF(V600E. We employed Illumina GoldenGate DNA methylation technology, which interrogates 1,505 CpG sites in 807 different genes, to further study this association. We first examined whether expression of BRAF(V600E causes DNA hypermethylation by stably expressing BRAF(V600E in the CIMP-negative, BRAF wild-type COLO 320DM colorectal cancer cell line. We determined 100 CIMP-associated CpG sites and examined changes in DNA methylation in eight stably transfected clones over multiple passages. We found that BRAF(V600E is not sufficient to induce CIMP in our system. Secondly, considering the alternative possibility, we identified genes whose DNA hypermethylation was closely linked to BRAF(V600E and CIMP in 235 primary colorectal tumors. Interestingly, genes that showed the most significant link include those that mediate various signaling pathways implicated in colorectal tumorigenesis, such as BMP3 and BMP6 (BMP signaling, EPHA3, KIT, and FLT1 (receptor tyrosine kinases and SMO (Hedgehog signaling. Furthermore, we identified CIMP-dependent DNA hypermethylation of IGFBP7, which has been shown to mediate BRAF(V600E-induced cellular senescence and apoptosis. Promoter DNA hypermethylation of IGFBP7 was associated with silencing of the gene. CIMP-specific inactivation of BRAF(V600E-induced senescence and apoptosis pathways by IGFBP7 DNA hypermethylation might create a favorable context for the acquisition of BRAF(V600E in CIMP+ colorectal cancer. Our data will be useful for future investigations toward
Lancashire, L J; Powe, D G; Reis-Filho, J S; Rakha, E; Lemetre, C; Weigelt, B; Abdel-Fatah, T M; Green, A R; Mukta, R; Blamey, R; Paish, E C; Rees, R C; Ellis, I O; Ball, G R
Gene expression microarrays allow for the high throughput analysis of huge numbers of gene transcripts and this technology has been widely applied to the molecular and biological classification of cancer patients and in predicting clinical outcome. A potential handicap of such data intensive molecular technologies is the translation to clinical application in routine practice. In using an artificial neural network bioinformatic approach, we have reduced a 70 gene signature to just 9 genes capable of accurately predicting distant metastases in the original dataset. Upon validation in a follow-up cohort, this signature was an independent predictor of metastases free and overall survival in the presence of the 70 gene signature and other factors. Interestingly, the ANN signature and CA9 expression also split the groups defined by the 70 gene signature into prognostically distinct groups. Subsequently, the presence of protein for the principal prognosticator gene was categorically assessed in breast cancer tissue of an experimental and independent validation patient cohort, using immunohistochemistry. Importantly our principal prognosticator, CA9, showed that it is capable of selecting an aggressive subgroup of patients who are known to have poor prognosis.
Full Text Available Introduction: This increased risk of bacterial infections in the cancer patient is further compounded by the rising trends of antibiotic resistance in commonly implicated organisms. In the Indian setting this is particularly true in case of Gram negative bacilli such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. Increasing resistance among Gram positive organisms is also a matter of concern. The aim of this study was to document the common organisms isolated from bacterial infections in cancer patients and describe their antibiotic susceptibilities. Methods: We conducted a 6 month study of all isolates from blood, urine, skin/soft tissue and respiratory samples of patients received from medical and surgical oncology units in our hospital. All samples were processed as per standard microbiology laboratory operating procedures. Isolates were identified to species level and susceptibility tests were performed as per Clinical Laboratory Standards Institute (CLSI guidelines -2012. Results: A total of 285 specimens from medical oncology (114 and surgical oncology services (171 were cultured. Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Acinetobacter spp. were most commonly encountered. More than half of the Acinetobacter strains were resistant to carbapenems. Resistance in Klebsiella pneumoniae to cephalosporins, fluoroquinolones and carbapenems was >50%. Of the Staphylococcus aureus isolates 41.67% were methicillin resistant. Conclusion: There is, in general, a high level of antibiotic resistance among gram negative bacilli, particularly E. coli, Klebsiella pneumoniae and Acinetobacter spp. Resistance among Gram positives is not as acute, although the MRSA incidence is increasing.
Berg, Daniela; Hipp, Susanne; Malinowsky, Katharina; Böllner, Claudia; Becker, Karl-Friedrich
In most hospitals word-wide, histopathological cancer diagnosis is currently based on formalin-fixed and paraffin-embedded (FFPE) tissues. In the last few years new approaches and developments in patient-tailored cancer therapy have raised the need to select more precisely those patients, who will respond to personalised treatments. The most efficient way for optimal therapy and patient selection is probably to provide a tumour-specific protein network portrait prior to treatment. The discovery and characterisation of deregulated signalling molecules (e.g. human epidermal growth factor receptor 2, mitogen-activated protein kinases) are very promising candidates for the identification of new suitable therapy targets and for the selection of those patients who will receive the greatest benefit from individualised treatments. The reverse phase protein array (RPPA) is a promising new technology that allows quick, precise and simultaneous analysis of many components of a network. Importantly it requires only limited amounts of routine clinical material (e.g. FFPE biopsies) and can be used for absolute protein measurements. We and other research groups have described successful protein extraction from routine FFPE tissues. In this manuscript we show how these recent developments might facilitate the implementation of RPPA in clinical trials and routine settings.
Rahman, Anis; Rahman, Aunik K; Rao, Babar
Terahertz scanning reflectometry, terahertz 3D imaging and terahertz time-domain spectroscopy have been used to identify features in human skin biopsy samples diagnosed for basal cell carcinoma (BCC) and compared with healthy skin samples. It was found from the 3D images that the healthy skin samples exhibit regular cellular pattern while the BCC skin samples indicate lack of regular cell pattern. The skin is a highly layered structure organ; this is evident from the thickness profile via a scan through the thickness of the healthy skin samples, where, the reflected intensity of the terahertz beam exhibits fluctuations originating from different skin layers. Compared to the healthy skin samples, the BCC samples' profiles exhibit significantly diminished layer definition; thus indicating a lack of cellular order. In addition, terahertz time-domain spectroscopy reveals significant and quantifiable differences between the healthy and BCC skin samples. Thus, a combination of three different terahertz techniques constitutes a conclusive route for detecting the BCC condition on a cellular level compared to the healthy skin.
孙亚丽; 王继红; 于天荣
Objective To investigate influences of the application of Watson ’ s nursing theory by community nursing staff on the life quality of cancer patients living at home. Methods The quality life and the happiness index of 107 patients with cancer were evaluated on the basis of a life quality scale(SF-36) according to Watson’ s nursing theory. Results The scores of the quality of life in 8 dimensions after the application of Watson’ s nursing theory in patients with cancer living at home showed significant differences compared with those before the application ( P<0 . 01 or P<0 . 05 ) . Conclusion Watson ’ s nursing theory can significantly improve the quality of life in patients with cancer living at home.%目的：探讨社区护理人员采用华生照护理论对居家恶性肿瘤患者照护后生活质量的变化.方法应用(SF-36)量表对107名恶性肿瘤患者运用华生照护理论照护后的生活质量进行评估.结果在应用华生照护理论照护后，患者的生活质量在8个维度上的评分具有显著差异(P<0.01或P<0.05).结论采用华生照护理论照护可有效提高恶性肿瘤患者生活质量.
Hamam, Rimi; Ali, Arwa M.; Alsaleh, Khalid A.;
Breast cancer (BC) is the most common cancer type and the second cause of cancer-related death among women. Therefore, better understanding of breast cancer tumor biology and the identification of novel biomarkers is essential for the early diagnosis and for better disease stratification and mana......Breast cancer (BC) is the most common cancer type and the second cause of cancer-related death among women. Therefore, better understanding of breast cancer tumor biology and the identification of novel biomarkers is essential for the early diagnosis and for better disease stratification...... and management choices. Herein we developed a novel approach which relies on the isolation of circulating microRNAs through an enrichment step using speed-vacuum concentration which resulted in 5-fold increase in microRNA abundance. Global miRNA microarray expression profiling performed on individual samples...... of 46 BC and 14 controls. The expression of those microRNAs was overall higher in patients with stage I, II, and III, compared to stage IV, with potential utilization for early detection. The expression of this microRNA panel was slightly higher in the HER2 and TN compared to patients with luminal...
Woolman, Michael; Tata, Alessandra; Bluemke, Emma; Dara, Delaram; Ginsberg, Howard J.; Zarrine-Afsar, Arash
Mass spectrometry imaging with desorption electrospray ionization mass spectrometry (DESI-MS) is used to characterize cancer from ex vivo slices of tissues. The process is time-consuming. The use of tissue smears for DESI-MS analysis has been proposed as it eliminates the time required to snap-freeze and section the tissue. To assess the utility of tissue smears for rapid cancer characterization, principal component analysis (PCA) was performed to evaluate the concordance between DESI-MS profiles of breast cancer from tissue slices and smears prepared on various surfaces. PCA suggested no statistical discrimination between DESI-MS profiles of tissue sections and tissue smears prepared on glass, polytetrafluoroethylene (PTFE), and porous PTFE. However, the abundances of cancer biomarker ions varied between sections and smears, with DESI-MS analysis of tissue sections yielding higher ion abundances of cancer biomarkers compared with smears. Coefficient of variance (CV) analysis suggests DESI-MS profiles from tissue smears are as reproducible as the ones from tissue sections. The limit of detection with smear samples from single pixel analysis is comparable to tissue sections that average the signal from a tissue area of 0.01 mm2. The smears prepared on the PTFE surface possessed a higher degree of homogeneity compared with the smears prepared on the glass surface. This allowed single MS scans ( 1 s) from random positions across the surface of the smear to be used in rapid cancer typing with good reproducibility, providing pathologic information for cancer typing at speeds suitable for clinical utility.
Yong Mao; Xiao-Bo Zhou; Dao-Ying Pi; You-Xian Sun
In this study, we present a constructive algorithm for training cooperative support vector machine ensembles (CSVMEs). CSVME combines ensemble architecture design with cooperative training for individual SVMs in ensembles. Unlike most previous studies on training ensembles, CSVME puts emphasis on both accuracy and collaboration among individual SVMs in an ensemble. A group of SVMs selected on the basis of recursive classifier elimination is used in CSVME, and the number of the individual SVMs selected to construct CSVME is determined by 10-fold cross-validation. This kind of SVME has been tested on two ovarian cancer datasets previously obtained by proteomic mass spectrometry. By combining several individual SVMs, the proposed method achieves better performance than the SVME of all base SVMs.
Malik Tariq Rasool
Results: Most of the patients were in the age group of 41–60 years and there was no gender preponderance in patients. Female breast cancer was the most common incident (15.5% malignancy followed by multiple myeloma, lung, and prostatic carcinoma. Lower dorsal spine was the most common site of compression (35% followed by lumbar (31% and mid-dorsal (26% spine. 70 (91% patients had cord compression subsequent to bone metastasis while as other patients had leptomeningeal metastasis. In 31 (40% patients, spinal cord compression was the presenting symptom. Overall, only 26 patients had motor improvement after treatment. Conclusion: Grade of power before treatment was predictive of response to treatment and overall outcome of motor or sensory functions. Neurodeficit of more than 10 days duration was associated with poor outcome in neurological function.
Yoshie, Tomoo; Nishiumi, Shin; Izumi, Yoshihiro; Sakai, Aya; Inoue, Jun; Azuma, Takeshi; Yoshida, Masaru
Mutation of the APC gene occurs during the early stages of colorectal cancer development. To obtain new insights into the mechanisms underlying the aberrant activation of the Wnt pathway that accompanies APC mutation, we carried out a gas chromatography-mass spectrometry-based semiquantitative metabolome analysis. In vitro experiments comparing SW480 cells expressing normal APC and truncated APC indicated that the levels of metabolites involved in the latter stages of the intracellular tricarboxylic acid cycle, including succinic acid, fumaric acid, and malic acid, were significantly higher in the SW480 cells expressing the truncated APC. In an in vivo study, we found that the levels of most amino acids were higher in the non-polyp tissues of APC(min/+) mice than in the normal tissues of the control mice and the polyp tissues of APC(min/+) mice. Ribitol, the levels of which were decreased in the polyp lesions of the APC(min/+) mice and the SW480 cells expressing the truncated APC, reduced the growth of SW480 cells with the APC mutation, but did not affect the growth of SW480 transfectants expressing full-length APC. The level of sarcosine was found to be significantly higher in the polyp tissues of APC(min/+) mice than in their non-polyp tissues and the normal tissues of the control mice, and the treatment of SW480 cells with 50 μM sarcosine resulted in a significant increase in their growth rate. These findings suggest that APC mutation causes changes in energetic metabolite pathways and that these alterations might be involved in the development of colorectal cancer.
Full Text Available BACKGROUND: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, the complexity of body fluids often hampers biomarker discovery. An attractive alternative approach is the isolation of small vesicles, i.e. exosomes, ∼100 nm, which contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific biomarker discovery. 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. After tryptic digestion, proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS mode. Accurate Mass and Time (AMT tag approach was employed for peptide identification and quantitation. Candidate biomarkers were validated by Western blotting and Immunohistochemistry. RESULTS: Proteomic characterization resulted in the identification of 248, 233, 169, and 216 proteins by at least 2 peptides in exosomes from PNT2C2, RWPE-1, PC346C, and VCaP, respectively. Statistical analyses revealed 52 proteins differently abundant 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. CONCLUSIONS: Identification of exosomal proteins using high performance LC-FTMS resulted in the discovery of PDCD6IP, FASN, XPO1 and ENO1 as new candidate biomarkers for prostate cancer.
Bahena-Román, Margarita; Téllez-Sosa, Juan; Martínez-Barnetche, Jesús; Cortina-Ceballos, Bernardo; López-Estrada, Guillermina; Delgado-Romero, Karina; Burguete-García, Ana I.; Cantú, David; García-Carrancá, Alejandro; Madrid-Marina, Vicente
Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When β-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006) and the largest distance compared to NCL-HPV negative ones (p<0.00001). The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings. PMID:27115350
The Oncology Nursing Society and the American Society of Clinical Oncology have established guidelines for the safe and effective use of chemotherapeutic medications in the acute and outpatient care settings. A review of literature was performed to determine the safe and effective administration of chemotherapy in the home environment. The administration of oral and intravenous chemotherapy in the home has become a common intervention for patients being treated for cancer based on patient preference, cost-effectiveness of healthcare delivery, and increasing demand for oncology services. Home healthcare nurses can greatly impact the management of adverse effects of chemotherapy in the home, increasing the quality of life and improving patient outcomes.
van Suylen Robert-Jan
Full Text Available Abstract Background Selection of early stage non-small cell lung cancer patients with a high risk of recurrence is warranted in order to select patients who will benefit from adjuvant treatment strategies. We evaluated the prognostic value of integrin expression profiles in a retrospective study on frozen primary tumors of 68 patients with early stage non-small cell lung cancer. Methods A retrospective study was performed on frozen primary tumors of 68 early stage non-small cell lung cancer patients with a follow up of at least 10 years. From all tumor tissues, RNA was isolated and reverse transcribed into cDNA. qPCR was used to generate mRNA expression profiles including integrins alpha1, 2, 3, 4, 5, 6, 7, 11, and V as well as integrins beta1, 3, 4, 5, 6, and 8. Results The expression levels of integrins alpha5, beta1 and beta3 predicted overall survival and disease free survival in early stage NSCLC patients. There was no association between integrin expression and lymph node metastases. Comparison between the histological subtypes revealed a distinct integrin signature for squamous cell carcinoma while the profiles of adenocarcinoma and large cell carcinoma were largely the same. Conclusion Integrin expression in NSCLC is important for the development and behavior of the tumor and influences the survival of the patient. Determining the integrin expression profile might serve as a tool in predicting the prognosis of individual patients.
许沈华; 牟瀚舟; 吕桂泉; 朱赤红; 羊正炎; 高永良; 楼洪坤; 刘祥麟; 程勇; 杨文
Objectives To study the difference between gene expressions of high (H0-8910PM) and low (HO-8910) metastatic human ovarian carcinoma cell lines and screen novel associated genes by cDNA microarray. Methods cDNA retro-transcribed from equal quantities of mRNA derived from high and low metastatic tumor cells or normal ovarian tissues were labeled with Cy5 and Cy3 fluorescein as probes. The mixed probe was hybridized with two pieces of BioDoor 4096 double dot human whole gene chip and scanned with a ScanArray 3000 laser scanner. The acquired image was analyzed by ImaGene 3.0 software. Results A total of 355 genes with expression levels more than 3 times larger were found by comparing the HO-8910 cell with normal ovarian epithelial cells. A total of 323 genes with expression levels more than 3 times larger in HO-8910PM cells compared to normal ovarian epithelium cells were also detected. A total of 165 genes whose expression levels were more than two times those of HO-8910PM cells compared to their mother cell line (HO-8910) were detected. Twenty-one genes with expression levels >3 times were found from comparison of these two tumor cell lines.Conclusions cDNA microarray techniques are effective in screening differential gene expression between two human ovarian cancer cell lines (H0-8910PM; HO-8910) and normal ovarian epithelial cells. These genes may be related to the genesis and development of ovarian carcinoma. Analysis of the human ovarian cancer gene expression profile with cDNA microarray may help in gene diagnosis, treatment and prevention.
Asara, Yolande; Marchal, Juan A; Carrasco, Esther; Boulaiz, Houria; Solinas, Giuliana; Bandiera, Pasquale; Garcia, Maria A; Farace, Cristiano; Montella, Andrea; Madeddu, Roberto
Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd), which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU) is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.
Full Text Available Industrialisation, the proximity of factories to cities, and human work activities have led to a disproportionate use of substances containing heavy metals, such as cadmium (Cd, which may have deleterious effects on human health. Carcinogenic effects of Cd and its relationship with breast cancer, among other tumours, have been reported. 5-Fluorouracil (5-FU is a fluoropyrimidine anticancer drug used to treat solid tumours of the colon, breast, stomach, liver, and pancreas. The purpose of this work was to study the effects of Cd on cell cycle, apoptosis, and gene and protein expression in MCF-7 breast cancer cells treated with 5-FU. Cd altered the cell cycle profile, and its effects were greater when used either alone or in combination with 5-FU compared with 5-FU alone. Cd significantly suppressed apoptosis of MCF-7 cells pre-treated with 5-FU. Regarding gene and protein expression, bcl2 expression was mainly upregulated by all treatments involving Cd. The expression of caspase 8 and caspase 9 was decreased by most of the treatments and at all times evaluated. C-myc expression was increased by all treatments involving Cd, especially 5-FU plus Cd at the half time of treatment. Cd plus 5-FU decreased cyclin D1 and increased cyclin A1 expression. In conclusion, our results indicate that exposure to Cd blocks the anticancer effects of 5-FU in MCF-7 cells. These results could have important clinical implications in patients treated with 5-FU-based therapies and who are exposed to high levels of Cd.
Jessica A. Engel
Full Text Available Histone deacetylase (HDAC enzymes work together with histone acetyltransferases (HATs to reversibly acetylate both histone and non-histone proteins. As a result, these enzymes are involved in regulating chromatin structure and gene expression as well as other important cellular processes. HDACs are validated drug targets for some types of cancer, with four HDAC inhibitors clinically approved. However, they are also showing promise as novel drug targets for other indications, including malaria and other parasitic diseases. In this study the in vitro activity of four anti-cancer HDAC inhibitors was examined against parasites that cause malaria and trypanosomiasis. Three of these inhibitors, suberoylanilide hydroxamic acid (SAHA; vorinostat®, romidepsin (Istodax® and belinostat (Beleodaq®, are clinically approved for the treatment of T-cell lymphoma, while the fourth, panobinostat, has recently been approved for combination therapy use in certain patients with multiple myeloma. All HDAC inhibitors were found to inhibit the growth of asexual-stage Plasmodium falciparum malaria parasites in the nanomolar range (IC50 10–200 nM, while only romidepsin was active at sub-μM concentrations against bloodstream form Trypanosoma brucei brucei parasites (IC50 35 nM. The compounds were found to have some selectivity for malaria parasites compared with mammalian cells, but were not selective for trypanosome parasites versus mammalian cells. All compounds caused hyperacetylation of histone and non-histone proteins in P. falciparum asexual stage parasites and inhibited deacetylase activity in P. falciparum nuclear extracts in addition to recombinant PfHDAC1 activity. P. falciparum histone hyperacetylation data indicate that HDAC inhibitors may differentially affect the acetylation profiles of histone H3 and H4.
Engel, Jessica A; Jones, Amy J; Avery, Vicky M; Sumanadasa, Subathdrage D M; Ng, Susanna S; Fairlie, David P; Adams, Tina S; Andrews, Katherine T
Histone deacetylase (HDAC) enzymes work together with histone acetyltransferases (HATs) to reversibly acetylate both histone and non-histone proteins. As a result, these enzymes are involved in regulating chromatin structure and gene expression as well as other important cellular processes. HDACs are validated drug targets for some types of cancer, with four HDAC inhibitors clinically approved. However, they are also showing promise as novel drug targets for other indications, including malaria and other parasitic diseases. In this study the in vitro activity of four anti-cancer HDAC inhibitors was examined against parasites that cause malaria and trypanosomiasis. Three of these inhibitors, suberoylanilide hydroxamic acid (SAHA; vorinostat(®)), romidepsin (Istodax(®)) and belinostat (Beleodaq(®)), are clinically approved for the treatment of T-cell lymphoma, while the fourth, panobinostat, has recently been approved for combination therapy use in certain patients with multiple myeloma. All HDAC inhibitors were found to inhibit the growth of asexual-stage Plasmodium falciparum malaria parasites in the nanomolar range (IC50 10-200 nM), while only romidepsin was active at sub-μM concentrations against bloodstream form Trypanosoma brucei brucei parasites (IC50 35 nM). The compounds were found to have some selectivity for malaria parasites compared with mammalian cells, but were not selective for trypanosome parasites versus mammalian cells. All compounds caused hyperacetylation of histone and non-histone proteins in P. falciparum asexual stage parasites and inhibited deacetylase activity in P. falciparum nuclear extracts in addition to recombinant PfHDAC1 activity. P. falciparum histone hyperacetylation data indicate that HDAC inhibitors may differentially affect the acetylation profiles of histone H3 and H4.