Jacintha O'Sullivan

Bio: Jacintha O'Sullivan is an academic researcher from Trinity College, Dublin. The author has contributed to research in topics: Cancer & Colorectal cancer. The author has an hindex of 39, co-authored 152 publications receiving 4599 citations. Previous affiliations of Jacintha O'Sullivan include Oklahoma State University Center for Health Sciences & University College Dublin.

Heterogeneity of tumor-induced gene expression changes in the human metabolic network

Abstract: Reprogramming of cellular metabolism is an emerging hallmark of neoplastic transformation. However, it is not known how metabolic gene expression in tumors differs from that in normal tissues, or whether different tumor types exhibit similar metabolic changes. Here we compare expression patterns of metabolic genes across 22 diverse types of human tumors. Overall, the metabolic gene expression program in tumors is similar to that in the corresponding normal tissues. Although expression changes of some metabolic pathways (e.g., up-regulation of nucleotide biosynthesis and glycolysis) are frequently observed across tumors, expression changes of other pathways (e.g., oxidative phosphorylation and the tricarboxylic acid (TCA) cycle) are very heterogeneous. Our analysis also suggests that the expression changes of major metabolic processes across tumors can be rationalized in terms of several principal components. On the level of individual biochemical reactions, many hundreds of metabolic isoenzymes show significant and tumor-specific expression changes. These isoenzymes are potential targets for anticancer therapy.

Chromosomal instability in ulcerative colitis is related to telomere shortening.

Abstract: Ulcerative colitis, a chronic inflammatory disease of the colon, is associated with a high risk of colorectal carcinoma that is thought to develop through genomic instability. We considered that the rapid cell turnover and oxidative injury observed in ulcerative colitis might accelerate telomere shortening, thereby increasing the potential of chromosomal ends to fuse, resulting in cycles of chromatin bridge breakage and fusion and chromosomal instability associated with tumor cell progression. Here we have used quantitative fluorescence in situ hybridization to compare chromosomal aberrations and telomere shortening in non-dysplastic mucosa taken from individuals affected by ulcerative colitis, either with (UC progressors) or without (UC non-progressors) dysplasia or cancer. Losses, but not gains, of chromosomal arms and centromeres are highly correlated with telomere shortening. Chromosomal losses are greater and telomeres are shorter in biopsy samples from UC progressors than in those from UC non-progressors or control individuals without ulcerative colitis. A mechanistic link between telomere shortening and chromosomal instability is supported by a higher frequency of anaphase bridges--an intermediate in the breakage and fusion of chromatin bridges--in UC progressors than in UC non-progressors or control individuals. Our study shows that telomere length is correlated with chromosomal instability in a precursor of human cancer.

Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer.

Abstract: BackgroundTumor budding along the advancing front of colorectal adenocarcinoma is an early event in the metastatic process. A reproducible, prognostic budding scoring system based on outcomes in early stage colorectal cancer has not been established.DesignOne hundred twenty-eight T3N0M0 colorectal c

Synovial tissue hypoxia and inflammation in vivo

Abstract: Introduction Hypoxia is a microenvironmental feature in the inflamed joint, which promotes survival advantage for cells. The aim of this study was to examine the relationship of partial oxygen pressure in the synovial tissue (tPO 2 ) in patients with inflammatory arthritis with macroscopic/microscopic inflammation and local levels of proinflammatory mediators. Methods Patients with inflammatory arthritis underwent full clinical assessment and video arthroscopy to quantify macroscopic synovitis and measure synovial tPO 2 under direct visualisation. Cell specific markers (CD3 (T cells), CD68 (macrophages), Ki67 (cell proliferation) and terminal deoxynucleotidyl transferase dUTP nick end labelling (cell apoptosis)) were quantified by immunohistology. In vitro migration was assessed in primary and normal synoviocytes (synovial fibroblast cells (SFCs)) using a wound repair scratch assay. Levels of tumour necrosis factor α (TNFα), interleukin 1β (IL1β), interferon γ (IFNγ), IL6, macrophage inflammatory protein 3α (MIP3α) and IL8 were quantified, in matched serum and synovial fluid, by multiplex cytokine assay and ELISA. Results The tPO 2 was 22.5 (range 3.2–54.1) mm Hg and correlated inversely with macroscopic synovitis (r=−0.421, p=0.02), sublining CD3 cells (−0.611, p 2 in vivo) induced cell migration. This was coupled with significantly higher levels of synovial fluid tumour necrosis factor α (TNFα), IL1β, IFNγ and MIP3α in patients with tPO 2 Conclusions This is the first study to show a direct in vivo correlation between synovial tPO 2 , inflammation and cell migration, thus it is proposed that hypoxia is a possible primary driver of inflammatory processes in the arthritic joint.

Development and Independent Validation of a Prognostic Assay for Stage II Colon Cancer Using Formalin-Fixed Paraffin-Embedded Tissue

Abstract: Purpose Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray‐based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples. Patients and Methods A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery. Results The 634‐probe set signature identified high-risk patients with a hazard ratio (HR) of 2.62 (P .001) during cross validation of the training set. In an independent validation set of 144 samples, the signature identified high-risk patients with an HR of 2.53 (P .001) for recurrence and an HR of 2.21 (P .0084) for cancer-related death. Additionally, the signature was shown to perform independently from known prognostic factors (P .001).

Food, Nutrition, Physical Activity, and the Prevention of Cancer : a Global Perspective : 食物、栄養、身体活動とがんの予防 : 世界的展望(後篇)

Abstract: physical activity and cancer fact sheet national cancer on this page what is physical activity what is known about the relationship between physical activity and cancer risk how might physical activity be, diet and cancer report american institute for cancer the american institute for cancer research aicr is the cancer charity that fosters research on diet and cancer prevention and educates the public about the results, download resources and toolkits world cancer research downloads for scientists from the wcrf aicr third expert report diet nutrition physical activity and cancer a global perspective, nutritional science university of washington school of public health school of public health nutritional science detailed course offerings time schedule are available for spring quarter 2019, 2019 aicr research conference american institute for about aicr we fund cutting edge research and give people practical tools and information to help them prevent and survive cancer more about aicr, agence fruits et l gumes frais aprifel the global fruit and veg newsletter is a monthly newsletter distributing to 29 countries involved in the promotion of the consumption of fruit and vegetable worldwide, world cancer research fund international we are experts in cancer prevention we analyse global research on diet nutrition physical activity cancer and make public health policy recommendations, the fractions of cancer attributable sciencedirect com a proportion of cancers at many body sites are attributable to potentially modifiable factors no global summaries of the preventable cancer burden have been, who controlling the global obesity epidemic more information obesity and overweight fact sheet who global strategy on diet physical activity and health who global database on body mass index, espen guidelines on nutrition in cancer patients gl nutrition in cancer patients outline o methods o1 basic information o2 methods o3 post publication impact a background a1 catabolic alterations in, un news global perspective human stories un news produces daily news content in arabic chinese english french kiswahili portuguese russian and spanish and weekly programmes in hindi urdu and bangla, recommended community strategies and measurements to table continued summary of recommended community strategies and measurements to prevent obesity in the united states strategies to encourage physical, food as medicine preventing treating the most dreaded food as medicine preventing treating the most dreaded diseases with diet, video resources bc cancer these videos help patients learn about their cancer and its treatment, prostate cancer nutrition and dietary supplements pdq nutrition methods and dietary supplements have been studied for prostate cancer prevention or treatment read about the history of research laboratory, who europe food safety food safety ingestion and handling of contaminated food causes significant illness and death worldwide across the who european region foodborne diseases, creating healthy food and eating environments policy and food and eating environments likely contribute to the increasing epidemic of obesity and chronic diseases over and above individual factors such as knowledge skills, health risks obesity prevention source harvard t h obesity and reproduction obesity can influence various aspects of reproduction from sexual activity to conception among women the association between, top nutrition schools undergraduate degree programs ncr want to know the top nutrition schools and best undergraduate degree programs here we review analyze rank rate them figure out which is best for you , overeating caloric restriction and breast cancer risk by this study analyzes the association of excessive energy intake and caloric restriction with breast cancer bc risk taking into account the individual, calcium what s best for your bones and health the possible increased risk of ovarian cancer high levels of galactose a sugar released by the digestion of lactose in milk have been studied as being, cancer protocol nutrition supplements cancer protocol nutrition supplements herbs enzymes note do not email me unless you would like a personalized protocol free with a suggested donation of 250

Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

Abstract: PLoS BIOLOGY Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor Jean-Philippe Coppe 1 , Christopher K. Patil 1[ , Francis Rodier 1,2[ , Yu Sun 3 , Denise P. Mun oz 1,2 , Joshua Goldstein 1¤ , Peter S. Nelson 3 , Pierre-Yves Desprez 1,4 , Judith Campisi 1,2* 1 Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America, 2 Buck Institute for Age Research, Novato, California, United States of America, 3 Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 4 California Pacific Medical Center Research Institute, San Francisco, California, United States of America Cellular senescence suppresses cancer by arresting cell proliferation, essentially permanently, in response to oncogenic stimuli, including genotoxic stress. We modified the use of antibody arrays to provide a quantitative assessment of factors secreted by senescent cells. We show that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy. This senescence-associated secretory phenotype (SASP) developed slowly over several days and only after DNA damage of sufficient magnitude to induce senescence. Remarkably similar SASPs developed in normal fibroblasts, normal epithelial cells, and epithelial tumor cells after genotoxic stress in culture, and in epithelial tumor cells in vivo after treatment of prostate cancer patients with DNA- damaging chemotherapy. In cultured premalignant epithelial cells, SASPs induced an epithelial–mesenchyme transition and invasiveness, hallmarks of malignancy, by a paracrine mechanism that depended largely on the SASP factors interleukin (IL)-6 and IL-8. Strikingly, two manipulations markedly amplified, and accelerated development of, the SASPs: oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells, and functional loss of the p53 tumor suppressor protein. Both loss of p53 and gain of oncogenic RAS also exacerbated the promalignant paracrine activities of the SASPs. Our findings define a central feature of genotoxic stress-induced senescence. Moreover, they suggest a cell-nonautonomous mechanism by which p53 can restrain, and oncogenic RAS can promote, the development of age-related cancer by altering the tissue microenvironment. Citation: Coppe JP, Patil CK, Rodier F, Sun Y, Mun oz DP, et al. (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6(12): e301. doi:10.1371/journal.pbio.0060301 Introduction Cancer is a multistep disease in which cells acquire increasingly malignant phenotypes. These phenotypes are acquired in part by somatic mutations, which derange normal controls over cell proliferation (growth), survival, invasion, and other processes important for malignant tumorigenesis [1]. In addition, there is increasing evidence that the tissue microenvironment is an important determinant of whether and how malignancies develop [2,3]. Normal tissue environ- ments tend to suppress malignant phenotypes, whereas abnormal tissue environments such at those caused by inflammation can promote cancer progression. Cancer development is restrained by a variety of tumor suppressor genes. Some of these genes permanently arrest the growth of cells at risk for neoplastic transformation, a process termed cellular senescence [4–6]. Two tumor suppressor pathways, controlled by the p53 and p16INK4a/pRB proteins, regulate senescence responses. Both pathways integrate multiple aspects of cellular physiology and direct cell fate towards survival, death, proliferation, or growth arrest, depending on the context [7,8]. Several lines of evidence indicate that cellular senescence is a potent tumor-suppressive mechanism [4,9,10]. Many poten- tially oncogenic stimuli (e.g., dysfunctional telomeres, DNA PLoS Biology | www.plosbiology.org damage, and certain oncogenes) induce senescence [6,11]. Moreover, mutations that dampen the p53 or p16INK4a/pRB pathways confer resistance to senescence and greatly increase cancer risk [12,13]. Most cancers harbor mutations in one or both of these pathways [14,15]. Lastly, in mice and humans, a senescence response to strong mitogenic signals, such as those delivered by certain oncogenes, prevents premalignant lesions from progressing to malignant cancers [16–19]. Academic Editor: Julian Downward, Cancer Research UK, United Kingdom Received June 27, 2008; Accepted October 22, 2008; Published December 2, 2008 Copyright: O 2008 Coppe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abbreviations: CM, conditioned medium; DDR, DNA damage response; ELISA, enzyme-linked immunosorbent assay; EMT, epithelial–mesenchymal transition; GSE, genetic suppressor element; IL, interleukin; MIT, mitoxantrone; PRE, presenescent; PrEC, normal human prostate epithelial cell; REP, replicative exhaustion; SASP, senescence-associated secretory phenotype; SEN, senescent; shRNA, short hairpin RNA; XRA, X-irradiation * To whom correspondence should be addressed. E-mail: jcampisi@lbl.gov [ These authors contributed equally to this work. ¤ Current address: Genomics Institute of the Novartis Research Foundation, San Diego, California, United States of America December 2008 | Volume 6 | Issue 12 | e301

Radical causes of cancer

Abstract: Free radicals are ubiquitous in our body and are generated by normal physiological processes, including aerobic metabolism and inflammatory responses, to eliminate invading pathogenic microorganisms. Because free radicals can also inflict cellular damage, several defences have evolved both to protect our cells from radicals--such as antioxidant scavengers and enzymes--and to repair DNA damage. Understanding the association between chronic inflammation and cancer provides insights into the molecular mechanisms involved. In particular, we highlight the interaction between nitric oxide and p53 as a crucial pathway in inflammatory-mediated carcinogenesis.