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Sample records for cancer reduces transcriptome

  1. A transcriptome anatomy of human colorectal cancers

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    Lü, Bingjian; Xu, Jing; Lai, Maode; Zhang, Hao; Chen, Jian

    2006-01-01

    Accumulating databases in human genome research have enabled integrated genome-wide study on complicated diseases such as cancers. A practical approach is to mine a global transcriptome profile of disease from public database. New concepts of these diseases might emerge by landscaping this profile. In this study, we clustered human colorectal normal mucosa (N), inflammatory bowel disease (IBD), adenoma (A) and cancer (T) related expression sequence tags (EST) into UniGenes via an in-house GetUni software package and analyzed the transcriptome overview of these libraries by GOTree Machine (GOTM). Additionally, we downloaded UniGene based cDNA libraries of colon and analyzed them by Xprofiler to cross validate the efficiency of GetUni. Semi-quantitative RT-PCR was used to validate the expression of β-catenin and. 7 novel genes in colorectal cancers. The efficiency of GetUni was successfully validated by Xprofiler and RT-PCR. Genes in library N, IBD and A were all found in library T. A total of 14,879 genes were identified with 2,355 of them having at least 2 transcripts. Differences in gene enrichment among these libraries were statistically significant in 50 signal transduction pathways and Pfam protein domains by GOTM analysis P < 0.01 Hypergeometric Test). Genes in two metabolic pathways, ribosome and glycolysis, were more enriched in the expression profiles of A and IBD than in N and T. Seven transmembrane receptor superfamily genes were typically abundant in cancers. Colorectal cancers are genetically heterogeneous. Transcription variants are common in them. Aberrations of ribosome and glycolysis pathway might be early indicators of precursor lesions in colon cancers. The electronic gene expression profile could be used to highlight the integral molecular events in colorectal cancers

  2. Colorectal cancer stages transcriptome analysis.

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    Tianyao Huo

    Full Text Available Colorectal cancer (CRC is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differences in different stages of CRC. Gene expression data on 433 CRC patient samples were obtained from The Cancer Genome Atlas (TCGA. Gene expression differences were evaluated across CRC stages using linear regression. Genes with p≤0.001 in expression differences were evaluated further in principal component analysis and genes with p≤0.0001 were evaluated further in gene set enrichment analysis. A total of 377 patients with gene expression data in 20,532 genes were included in the final analysis. The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4 gene, which encodes for NIMA related kinase 4, was differentially expressed across the four stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10-6. Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and SPSB3 had p value of 0.0001 in the differential expression analysis. Principal component analysis indicated that the patients from the 4 clinical stages do not appear to have distinct gene expression pattern. Network-based and pathway-based gene set enrichment analyses showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein complex-based gene set analysis showed that four genes were involved in H2AX complex II. This study identified a small number of genes that might be associated with clinical stages of CRC. Our analysis was not able to find a molecular basis for the current clinical staging for CRC based on the gene expression patterns.

  3. Transcriptome

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    ... Also: Talking Glossary of Genetic Terms Definitions for genetic terms used on this page En Español: Transcriptoma Transcriptome What is a transcriptome? What can a transcriptome tell us? How can transcriptome data be used to explore gene function? What is ...

  4. A pathology atlas of the human cancer transcriptome

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    Uhlén, Mathias; Zhang, Xi-Cheng; Lee, Sunjae

    2017-01-01

    Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes o...

  5. Transcriptome complexity in a genome-reduced bacterium

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    Güell, Marc; van Noort, Vera; Yus, Eva

    2009-01-01

    To study basic principles of transcriptome organization in bacteria, we analyzed one of the smallest self-replicating organisms, Mycoplasma pneumoniae. We combined strand-specific tiling arrays, complemented by transcriptome sequencing, with more than 252 spotted arrays. We detected 117 previousl...

  6. Transcriptome sequencing in prostate cancer identifies inter-tumor heterogeneity

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    Janet Mendonca

    2015-06-01

    Full Text Available Given the dearth of gene mutations in prostate cancer, [1] ,[2] it is likely that genomic rearrangements play a significant role in the evolution of prostate cancer. However, in the search for recurrent genomic alterations, "private alterations" have received less attention. Such alterations may provide insights into the evolution, behavior, and clinical outcome of an individual tumor. In a recent report in "Genome Biology" Wyatt et al. [3] defines unique alterations in a cohort of high-risk prostate cancer patient with a lethal phenotype. Utilizing a transcriptome sequencing approach they observe high inter-tumor heterogeneity; however, the genes altered distill into three distinct cancer-relevant pathways. Their analysis reveals the presence of several non-ETS fusions, which may contribute to the phenotype of individual tumors, and have significance for disease progression.

  7. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.

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    Méplan, Catherine; Johnson, Ian T; Polley, Abigael C J; Cockell, Simon; Bradburn, David M; Commane, Daniel M; Arasaradnam, Ramesh P; Mulholland, Francis; Zupanic, Anze; Mathers, John C; Hesketh, John

    2016-08-01

    Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.-Méplan, C., Johnson, I. T., Polley, A. C. J., Cockell, S., Bradburn, D. M., Commane, D. M., Arasaradnam, R. P., Mulholland, F., Zupanic, A., Mathers, J. C., Hesketh, J. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies. © The Author(s).

  8. Transcriptomic and genomic features of invasive lobular breast cancer.

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    Desmedt, Christine; Zoppoli, Gabriele; Sotiriou, Christos; Salgado, Roberto

    2017-06-01

    Accounting for 10-15% of all breast neoplasms, invasive lobular breast cancer (ILC) is the second most common histological subtype of breast cancer after invasive ductal breast cancer (IDC). Understanding ILC biology, which differs from IDC in terms of clinical presentation, treatment response, relapse timing and patterns, is essential in order to adopt novel, disease-specific management strategies. While the contribution of the histological subtypes to tumour biology has been poorly investigated and acknowledged in the past, recently several major, independent efforts have led to the assembly and molecular characterization of well-annotated ILC case sets. In this review, we provide a critical overview of the literature exploring ILC, through comprehensive and multiomic methods. The first part specifically focuses on ILC transcriptomic features by reviewing the intrinsic molecular subtypes, the application of gene expression scores for the prediction of recurrence, and the identification of gene expression subtypes. The second part describes the main research efforts that lead to the identification of the genomic landscape of ILC, with a special focus to findings that differentiate ILC from IDC and carry potential clinical relevance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Integrated analysis of whole genome and transcriptome sequencing reveals diverse transcriptomic aberrations driven by somatic genomic changes in liver cancers.

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    Yuichi Shiraishi

    Full Text Available Recent studies applying high-throughput sequencing technologies have identified several recurrently mutated genes and pathways in multiple cancer genomes. However, transcriptional consequences from these genomic alterations in cancer genome remain unclear. In this study, we performed integrated and comparative analyses of whole genomes and transcriptomes of 22 hepatitis B virus (HBV-related hepatocellular carcinomas (HCCs and their matched controls. Comparison of whole genome sequence (WGS and RNA-Seq revealed much evidence that various types of genomic mutations triggered diverse transcriptional changes. Not only splice-site mutations, but also silent mutations in coding regions, deep intronic mutations and structural changes caused splicing aberrations. HBV integrations generated diverse patterns of virus-human fusion transcripts depending on affected gene, such as TERT, CDK15, FN1 and MLL4. Structural variations could drive over-expression of genes such as WNT ligands, with/without creating gene fusions. Furthermore, by taking account of genomic mutations causing transcriptional aberrations, we could improve the sensitivity of deleterious mutation detection in known cancer driver genes (TP53, AXIN1, ARID2, RPS6KA3, and identified recurrent disruptions in putative cancer driver genes such as HNF4A, CPS1, TSC1 and THRAP3 in HCCs. These findings indicate genomic alterations in cancer genome have diverse transcriptomic effects, and integrated analysis of WGS and RNA-Seq can facilitate the interpretation of a large number of genomic alterations detected in cancer genome.

  10. Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly.

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    Aramillo Irizar, Peer; Schäuble, Sascha; Esser, Daniela; Groth, Marco; Frahm, Christiane; Priebe, Steffen; Baumgart, Mario; Hartmann, Nils; Marthandan, Shiva; Menzel, Uwe; Müller, Julia; Schmidt, Silvio; Ast, Volker; Caliebe, Amke; König, Rainer; Krawczak, Michael; Ristow, Michael; Schuster, Stefan; Cellerino, Alessandro; Diekmann, Stephan; Englert, Christoph; Hemmerich, Peter; Sühnel, Jürgen; Guthke, Reinhard; Witte, Otto W; Platzer, Matthias; Ruppin, Eytan; Kaleta, Christoph

    2018-01-30

    Disease epidemiology during ageing shows a transition from cancer to degenerative chronic disorders as dominant contributors to mortality in the old. Nevertheless, it has remained unclear to what extent molecular signatures of ageing reflect this phenomenon. Here we report on the identification of a conserved transcriptomic signature of ageing based on gene expression data from four vertebrate species across four tissues. We find that ageing-associated transcriptomic changes follow trajectories similar to the transcriptional alterations observed in degenerative ageing diseases but are in opposite direction to the transcriptomic alterations observed in cancer. We confirm the existence of a similar antagonism on the genomic level, where a majority of shared risk alleles which increase the risk of cancer decrease the risk of chronic degenerative disorders and vice versa. These results reveal a fundamental trade-off between cancer and degenerative ageing diseases that sheds light on the pronounced shift in their epidemiology during ageing.

  11. Transcriptomics in cancer diagnostics: developments in technology, clinical research and commercialization.

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    Sager, Monica; Yeat, Nai Chien; Pajaro-Van der Stadt, Stefan; Lin, Charlotte; Ren, Qiuyin; Lin, Jimmy

    2015-01-01

    Transcriptomic technologies are evolving to diagnose cancer earlier and more accurately to provide greater predictive and prognostic utility to oncologists and patients. Digital techniques such as RNA sequencing are replacing still-imaging techniques to provide more detailed analysis of the transcriptome and aberrant expression that causes oncogenesis, while companion diagnostics are developing to determine the likely effectiveness of targeted treatments. This article examines recent advancements in molecular profiling research and technology as applied to cancer diagnosis, clinical applications and predictions for the future of personalized medicine in oncology.

  12. Meta-Transcriptomic Analysis of a Chromate-Reducing Aquifer Microbial Community

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    Beller, H. R.; Brodie, E. L.; Han, R.; Karaoz, U.

    2010-12-01

    A major challenge for microbial ecology that has become more tractable in the advent of new molecular techniques is characterizing gene expression in complex microbial communities. We are using meta-transcriptomic analysis to characterize functional changes in an aquifer-derived, chromate-reducing microbial community as it transitions through various electron-accepting conditions. We inoculated anaerobic microcosms with groundwater from the Cr-contaminated Hanford 100H site and supplemented them with lactate and electron acceptors present at the site, namely, nitrate, sulfate, and Fe(III). The microcosms progressed successively through various electron-accepting conditions (e.g., denitrifying, sulfate-reducing, and ferric iron-reducing conditions, as well as nitrate-dependent, chemolithotrophic Fe(II)-oxidizing conditions). Cr(VI) was rapidly reduced initially and again upon further Cr(VI) amendments. Extensive geochemical sampling and analysis (e.g., lactate, acetate, chloride, nitrate, nitrite, sulfate, dissolved Cr(VI), total Fe(II)), RNA/DNA harvesting, and PhyloChip analyses were conducted. Methods were developed for removal of rRNA from total RNA in preparation for meta-transcriptome sequencing. To date, samples representing denitrifying and fermentative/sulfate-reducing conditions have been sequenced using 454 Titanium technology. Of the non-rRNA related reads for the denitrifying sample (which was also actively reducing chromate), ca. 8% were associated with denitrification and ca. 0.9% were associated with chromate resistance/transport, in contrast to the fermentative/sulfate-reducing sample (in which chromate had already been reduced), which had zero reads associated with either of these categories but many predicted proteins associated with sulfate-reducing bacteria. We observed sequences for key functional transcripts that were unique at the nucleotide level compared to the GenBank non-redundant database [such as L-lactate dehydrogenase (iron

  13. Saccharomyces cerevisiae Boulardii Reduces the Deoxynivalenol-Induced Alteration of the Intestinal Transcriptome

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    Imourana Alassane-Kpembi

    2018-05-01

    Full Text Available Type B trichothecene mycotoxin deoxynivalenol (DON is one of the most frequently occurring food contaminants. By inducing trans-activation of a number of pro-inflammatory cytokines and increasing the stability of their mRNA, trichothecene can impair intestinal health. Several yeast products, especially Saccharomyces cerevisiae, have the potential for improving the enteric health of piglets, but little is known about the mechanisms by which the administration of yeast counteracts the DON-induced intestinal alterations. Using a pig jejunum explant model, a whole-transcriptome analysis was performed to decipher the early response of the small intestine to the deleterious effects of DON after administration of S. cerevisiae boulardii strain CNCM I-1079. Compared to the control condition, no differentially expressed gene (DE was observed after treatment by yeast only. By contrast, 3619 probes—corresponding to 2771 genes—were differentially expressed following exposure to DON, and 32 signaling pathways were identified from the IPA software functional analysis of the set of DE genes. When the intestinal explants were treated with S. cerevisiae boulardii prior to DON exposure, the number of DE genes decreased by half (1718 probes corresponding to 1384 genes. Prototypical inflammation signaling pathways triggered by DON, including NF-κB and p38 MAPK, were reversed, although the yeast demonstrated limited efficacy toward some other pathways. S. cerevisiae boulardii also restored the lipid metabolism signaling pathway, and reversed the down-regulation of the antioxidant action of vitamin C signaling pathway. The latter effect could reduce the burden of DON-induced oxidative stress. Altogether, the results show that S. cerevisiae boulardii reduces the DON-induced alteration of intestinal transcriptome, and point to new mechanisms for the healing of tissue injury by yeast.

  14. Saccharomyces cerevisiae Boulardii Reduces the Deoxynivalenol-Induced Alteration of the Intestinal Transcriptome.

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    Alassane-Kpembi, Imourana; Pinton, Philippe; Hupé, Jean-François; Neves, Manon; Lippi, Yannick; Combes, Sylvie; Castex, Mathieu; Oswald, Isabelle P

    2018-05-15

    Type B trichothecene mycotoxin deoxynivalenol (DON) is one of the most frequently occurring food contaminants. By inducing trans-activation of a number of pro-inflammatory cytokines and increasing the stability of their mRNA, trichothecene can impair intestinal health. Several yeast products, especially Saccharomyces cerevisiae , have the potential for improving the enteric health of piglets, but little is known about the mechanisms by which the administration of yeast counteracts the DON-induced intestinal alterations. Using a pig jejunum explant model, a whole-transcriptome analysis was performed to decipher the early response of the small intestine to the deleterious effects of DON after administration of S. cerevisiae boulardii strain CNCM I-1079. Compared to the control condition, no differentially expressed gene (DE) was observed after treatment by yeast only. By contrast, 3619 probes-corresponding to 2771 genes-were differentially expressed following exposure to DON, and 32 signaling pathways were identified from the IPA software functional analysis of the set of DE genes. When the intestinal explants were treated with S. cerevisiae boulardii prior to DON exposure, the number of DE genes decreased by half (1718 probes corresponding to 1384 genes). Prototypical inflammation signaling pathways triggered by DON, including NF-κB and p38 MAPK, were reversed, although the yeast demonstrated limited efficacy toward some other pathways. S. cerevisiae boulardii also restored the lipid metabolism signaling pathway, and reversed the down-regulation of the antioxidant action of vitamin C signaling pathway. The latter effect could reduce the burden of DON-induced oxidative stress. Altogether, the results show that S. cerevisiae boulardii reduces the DON-induced alteration of intestinal transcriptome, and point to new mechanisms for the healing of tissue injury by yeast.

  15. Benchmarking Water Quality from Wastewater to Drinking Waters Using Reduced Transcriptome of Human Cells.

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    Xia, Pu; Zhang, Xiaowei; Zhang, Hanxin; Wang, Pingping; Tian, Mingming; Yu, Hongxia

    2017-08-15

    One of the major challenges in environmental science is monitoring and assessing the risk of complex environmental mixtures. In vitro bioassays with limited key toxicological end points have been shown to be suitable to evaluate mixtures of organic pollutants in wastewater and recycled water. Omics approaches such as transcriptomics can monitor biological effects at the genome scale. However, few studies have applied omics approach in the assessment of mixtures of organic micropollutants. Here, an omics approach was developed for profiling bioactivity of 10 water samples ranging from wastewater to drinking water in human cells by a reduced human transcriptome (RHT) approach and dose-response modeling. Transcriptional expression of 1200 selected genes were measured by an Ampliseq technology in two cell lines, HepG2 and MCF7, that were exposed to eight serial dilutions of each sample. Concentration-effect models were used to identify differentially expressed genes (DEGs) and to calculate effect concentrations (ECs) of DEGs, which could be ranked to investigate low dose response. Furthermore, molecular pathways disrupted by different samples were evaluated by Gene Ontology (GO) enrichment analysis. The ability of RHT for representing bioactivity utilizing both HepG2 and MCF7 was shown to be comparable to the results of previous in vitro bioassays. Finally, the relative potencies of the mixtures indicated by RHT analysis were consistent with the chemical profiles of the samples. RHT analysis with human cells provides an efficient and cost-effective approach to benchmarking mixture of micropollutants and may offer novel insight into the assessment of mixture toxicity in water.

  16. Gene set-based module discovery in the breast cancer transcriptome

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    Zhang Michael Q

    2009-02-01

    Full Text Available Abstract Background Although microarray-based studies have revealed global view of gene expression in cancer cells, we still have little knowledge about regulatory mechanisms underlying the transcriptome. Several computational methods applied to yeast data have recently succeeded in identifying expression modules, which is defined as co-expressed gene sets under common regulatory mechanisms. However, such module discovery methods are not applied cancer transcriptome data. Results In order to decode oncogenic regulatory programs in cancer cells, we developed a novel module discovery method termed EEM by extending a previously reported module discovery method, and applied it to breast cancer expression data. Starting from seed gene sets prepared based on cis-regulatory elements, ChIP-chip data, and gene locus information, EEM identified 10 principal expression modules in breast cancer based on their expression coherence. Moreover, EEM depicted their activity profiles, which predict regulatory programs in each subtypes of breast tumors. For example, our analysis revealed that the expression module regulated by the Polycomb repressive complex 2 (PRC2 is downregulated in triple negative breast cancers, suggesting similarity of transcriptional programs between stem cells and aggressive breast cancer cells. We also found that the activity of the PRC2 expression module is negatively correlated to the expression of EZH2, a component of PRC2 which belongs to the E2F expression module. E2F-driven EZH2 overexpression may be responsible for the repression of the PRC2 expression modules in triple negative tumors. Furthermore, our network analysis predicts regulatory circuits in breast cancer cells. Conclusion These results demonstrate that the gene set-based module discovery approach is a powerful tool to decode regulatory programs in cancer cells.

  17. Intra-tumor heterogeneity in breast cancer has limited impact on transcriptomic-based molecular profiling.

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    Karthik, Govindasamy-Muralidharan; Rantalainen, Mattias; Stålhammar, Gustav; Lövrot, John; Ullah, Ikram; Alkodsi, Amjad; Ma, Ran; Wedlund, Lena; Lindberg, Johan; Frisell, Jan; Bergh, Jonas; Hartman, Johan

    2017-11-29

    Transcriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics. In this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications. Molecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications. Our results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.

  18. Identification of Human HK Genes and Gene Expression Regulation Study in Cancer from Transcriptomics Data Analysis

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    Zhang, Zhang; Liu, Jingxing; Wu, Jiayan; Yu, Jun

    2013-01-01

    The regulation of gene expression is essential for eukaryotes, as it drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms. RNA-Sequencing (RNA-Seq) provides researchers with a powerful toolbox for characterization and quantification of transcriptome. Many different human tissue/cell transcriptome datasets coming from RNA-Seq technology are available on public data resource. The fundamental issue here is how to develop an effective analysis method to estimate expression pattern similarities between different tumor tissues and their corresponding normal tissues. We define the gene expression pattern from three directions: 1) expression breadth, which reflects gene expression on/off status, and mainly concerns ubiquitously expressed genes; 2) low/high or constant/variable expression genes, based on gene expression level and variation; and 3) the regulation of gene expression at the gene structure level. The cluster analysis indicates that gene expression pattern is higher related to physiological condition rather than tissue spatial distance. Two sets of human housekeeping (HK) genes are defined according to cell/tissue types, respectively. To characterize the gene expression pattern in gene expression level and variation, we firstly apply improved K-means algorithm and a gene expression variance model. We find that cancer-associated HK genes (a HK gene is specific in cancer group, while not in normal group) are expressed higher and more variable in cancer condition than in normal condition. Cancer-associated HK genes prefer to AT-rich genes, and they are enriched in cell cycle regulation related functions and constitute some cancer signatures. The expression of large genes is also avoided in cancer group. These studies will help us understand which cell type-specific patterns of gene expression differ among different cell types, and particularly for cancer. PMID:23382867

  19. Whole-genome and Transcriptome Sequencing of Prostate Cancer Identify New Genetic Alterations Driving Disease Progression

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    Ren, Shancheng; Wei, Gong-Hong; Liu, Dongbing

    2018-01-01

    BACKGROUND: Global disparities in prostate cancer (PCa) incidence highlight the urgent need to identify genomic abnormalities in prostate tumors in different ethnic populations including Asian men. OBJECTIVE: To systematically explore the genomic complexity and define disease-driven genetic......-scale and comprehensive genomic data of prostate cancer from Asian population. Identification of these genetic alterations may help advance prostate cancer diagnosis, prognosis, and treatment....... alterations in PCa. DESIGN, SETTING, AND PARTICIPANTS: The study sequenced whole-genome and transcriptome of tumor-benign paired tissues from 65 treatment-naive Chinese PCa patients. Subsequent targeted deep sequencing of 293 PCa-relevant genes was performed in another cohort of 145 prostate tumors. OUTCOME...

  20. Meta-analysis of cancer transcriptomes: A new approach to uncover molecular pathological events in different cancer tissues

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    Sundus Iqbal

    2014-03-01

    Full Text Available To explore secrets of metastatic cancers, individual expression of true sets of respective genes must spread across the tissue. In this study, meta-analysis for transcriptional profiles of oncogenes was carried out to hunt critical genes or networks helping in metastasizing cancers. For this, transcriptomic analysis of different cancerous tissues causing leukemia, lung, liver, spleen, colorectal, colon, breast, bladder, and kidney cancers was performed by extracting microarray expression data from online resource; Gene Expression Omnibus. A newly developed bioinformatics technique; Dynamic Impact Approach (DIA was applied for enrichment analysis of transcriptional profiles using Database for Annotation Visualization and Integrated Discovery (DAVID. Furthermore, oPOSSUM (v. 2.0 and Cytoscape (v. 2.8.2 were used for in-depth analysis of transcription factors and regulatory gene networks respectively. DAVID analysis uncovered the most significantly enriched pathways in molecular functions that were 'Ubiquitin thiolesterase activity' up regulated in blood, breast, bladder, colorectal, lung, spleen, prostrate cancer. 'Transforming growth factor beta receptor activity' was inhibited in all cancers except leukemia, colon and liver cancer. oPOSSUM further revealed highly over-represented Transcription Factors (TFs; Broad-complex_3, Broad-complex_4, and Foxd3 except for leukemia and bladder cancer. From these findings, it is possible to target genes and networks, play a crucial role in the development of cancer. In the future, these transcription factors can serve as potential candidates for the therapeutic drug targets which can impede the deadly spread.

  1. Merging transcriptomics and metabolomics - advances in breast cancer profiling

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    Bathen Tone F

    2010-11-01

    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

  2. Merging transcriptomics and metabolomics - advances in breast cancer profiling

    International Nuclear Information System (INIS)

    Borgan, Eldrid; Sitter, Beathe; Lingjærde, Ole Christian; Johnsen, Hilde; Lundgren, Steinar; Bathen, Tone F; Sørlie, Therese; Børresen-Dale, Anne-Lise; Gribbestad, Ingrid S

    2010-01-01

    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. 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. 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 to choline. Additionally, a subset of transcripts was

  3. Does Metformin Reduce Cancer Risks? Methodologic Considerations.

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    Golozar, Asieh; Liu, Shuiqing; Lin, Joeseph A; Peairs, Kimberly; Yeh, Hsin-Chieh

    2016-01-01

    The substantial burden of cancer and diabetes and the association between the two conditions has been a motivation for researchers to look for targeted strategies that can simultaneously affect both diseases and reduce their overlapping burden. In the absence of randomized clinical trials, researchers have taken advantage of the availability and richness of administrative databases and electronic medical records to investigate the effects of drugs on cancer risk among diabetic individuals. The majority of these studies suggest that metformin could potentially reduce cancer risk. However, the validity of this purported reduction in cancer risk is limited by several methodological flaws either in the study design or in the analysis. Whether metformin use decreases cancer risk relies heavily on the availability of valid data sources with complete information on confounders, accurate assessment of drug use, appropriate study design, and robust analytical techniques. The majority of the observational studies assessing the association between metformin and cancer risk suffer from methodological shortcomings and efforts to address these issues have been incomplete. Future investigations on the association between metformin and cancer risk should clearly address the methodological issues due to confounding by indication, prevalent user bias, and time-related biases. Although the proposed strategies do not guarantee a bias-free estimate for the association between metformin and cancer, they will reduce synthesis of and reporting of erroneous results.

  4. Characterizing the Genetic Basis for Nicotine Induced Cancer Development: A Transcriptome Sequencing Study.

    Directory of Open Access Journals (Sweden)

    Jasmin H Bavarva

    Full Text Available Nicotine is a known risk factor for cancer development and has been shown to alter gene expression in cells and tissue upon exposure. We used Illumina® Next Generation Sequencing (NGS technology to gain unbiased biological insight into the transcriptome of normal epithelial cells (MCF-10A to nicotine exposure. We generated expression data from 54,699 transcripts using triplicates of control and nicotine stressed cells. As a result, we identified 138 differentially expressed transcripts, including 39 uncharacterized genes. Additionally, 173 transcripts that are primarily associated with DNA replication, recombination, and repair showed evidence for alternative splicing. We discovered the greatest nicotine stress response by HPCAL4 (up-regulated by 4.71 fold and NPAS3 (down-regulated by -2.73 fold; both are genes that have not been previously implicated in nicotine exposure but are linked to cancer. We also discovered significant down-regulation (-2.3 fold and alternative splicing of NEAT1 (lncRNA that may have an important, yet undiscovered regulatory role. Gene ontology analysis revealed nicotine exposure influenced genes involved in cellular and metabolic processes. This study reveals previously unknown consequences of nicotine stress on the transcriptome of normal breast epithelial cells and provides insight into the underlying biological influence of nicotine on normal cells, marking the foundation for future studies.

  5. Acupuncture Reduces Breast Cancer Joint Pain | Division of Cancer Prevention

    Science.gov (United States)

    In the largest, most rigorous study of its kind, acupuncture was found to significantly reduce the debilitating joint pain experienced by tens of thousands of women each year while being treated for early stage breast cancer with aromatase inhibitors (AIs). |

  6. Understanding and potentially reducing second breast cancer

    International Nuclear Information System (INIS)

    Brenner, D.

    2011-01-01

    Full text: Long term survival after breast cancer diagnosis has increased markedly in the last decade: 15-year relative survival after breast cancer diagnosis is now 75% in the US. Associated with these excellent survival prospects, however, long term studies suggest that contralateral second breast cancer rates are in the range from 10 to 15% at 15 years post treatment, and are still higher for BRCA1/2 carriers, as well as for still longer term survivors. These second cancer risks are much higher than those for a comparable healthy woman to develop a first breast cancer. It follows that women with breast cancer are highly prone to develop a second breast cancer. We propose here a new option for reducing the disturbingly high risk of a contralateral second breast cancer. in patients with both estrogen positive and negative primary breast cancer: prophylactic mammary irradiation (PMI) of the contralateral breast. The rationale behind PMI is evidence that standard post-Iumpectomy radiotherapy of the affected (ipsilateral) breast substantially reduces the long-term genetically-based second cancer risk in the ipsilateral breast, by killing the existing premalignant cells in that breast. This suggests that there are relatively few premalignant cells in the breast (hundreds or thousands, not millions), so even a fairly modest radiation cell-kill level across the whole breast would be expected to kill essentially all of them. If this is so, then a modest radiation dose-much lower than that to the affected breast--delivered uniformly to the whole contralateral breast, and typically delivered at the same time as the radiotherapy of the ipsilateral breast, would have the potential to markedly reduce second-cancer risks in the contralateral breast by killing essentially all the pre-malignant cells in that breast while causing only a very low level of radiation-induced sequelae. Therefore we hypothesize that low-dose prophylactic mammary irradiation of the contralateral breast

  7. Proteomic and transcriptomic profiling of in vitro established radiation resistant oral cancer cells for identification of radioresistance related biomarkers

    International Nuclear Information System (INIS)

    Mohd Yasser; Pawar, Sagar; Teni, Tanuja

    2016-01-01

    Radiotherapy is an integral part of oral cancer treatment, either alone or in combination with surgery. But, during radiotherapy, oral tumours of a subset of patients develop radioresistance that creates major obstruction towards its efficacy. The aim of our study was to establish radioresistant cell lines from different oral subsites using clinically admissible low dose radiation and profile them by proteomic and transcriptomic approaches to identify proteins associated with radioresistance in oral cancer

  8. Reducing milking frequency during nutrient restriction has no effect on the hepatic transcriptome of lactating dairy cattle.

    Science.gov (United States)

    Grala, T M; Kay, J K; Phyn, C V C; Bionaz, M; Walker, C G; Rius, A G; Snell, R G; Roche, J R

    2013-12-01

    The objective of this study was to investigate if a reduced milking frequency altered the effect of dietary energy restriction on the hepatic transcriptome of grazing dairy cows during early lactation. Multiparous Holstein-Friesian and Holstein-Friesian × Jersey cows (n = 120) were milked twice daily (2×) from calving until 34 ± 6 days in milk (mean ± SD). Cows were then allocated to one of four treatments in a 2 × 2 factorial arrangement. Treatments consisted of two milking frequencies [2× or once daily (1×)] and two feeding levels for 3 wk: adequately fed (AF) or underfed (UF, 60% of AF). Liver tissue was biopsied from 12 cows per treatment after 3 wk of treatment, and the hepatic transcriptome was profiled with an Agilent 4 × 44k bovine microarray. Over 2,900 genes were differentially expressed in response to the energy restriction; however, no effects resulted from changes to milking frequency. This may indicate that after 3 wk of 1× milking, any changes to the liver transcriptome that may have occurred earlier have returned to normal. After 3 wk of energy restriction, gene expression patterns indicate that glucose-sparing pathways were activated, and gluconeogenesis was increased in UF cows. Genes involved in hepatic stress were upregulated in response to the energy restriction indicative of the pressure energy restriction places on liver function. Other pathways upregulated included "cytoskeletal remodeling," indicating that a 3 wk energy restriction resulted in molecular changes to assist tissue remodeling. Overall, 1× milking does not modify the hepatic transcriptome changes that occur in response to an energy restriction.

  9. A functional and transcriptomic analysis of NET1 bioactivity in gastric cancer

    LENUS (Irish Health Repository)

    Bennett, Gayle

    2011-02-01

    Abstract Background NET1, a RhoA guanine exchange factor, is up-regulated in gastric cancer (GC) tissue and drives the invasive phenotype of this disease. In this study, we aimed to determine the role of NET1 in GC by monitoring the proliferation, motility and invasion of GC cells in which NET1 has been stably knocked down. Additionally, we aimed to determine NET1-dependent transcriptomic events that occur in GC. Methods An in vitro model of stable knockdown of NET1 was achieved in AGS human gastric adenocarcinoma cells via lentiviral mediated transduction of short-hairpin (sh) RNA targeting NET1. Knockdown was assessed using quantitative PCR. Cell proliferation was assessed using an MTS assay and cell migration was assessed using a wound healing scratch assay. Cell invasion was assessed using a transwell matrigel invasion assay. Gene expression profiles were examined using affymetrix oligonucleotide U133A expression arrays. A student\\'s t test was used to determine changes of statistical significance. Results GC cells were transduced with NET1 shRNA resulting in a 97% reduction in NET1 mRNA (p < 0.0001). NET1 knockdown significantly reduced the invasion and migration of GC cells by 94% (p < 0.05) and 24% (p < 0.001) respectively, while cell proliferation was not significantly altered following NET1 knockdown. Microarray analysis was performed on non-target and knockdown cell lines, treated with and without 10 μM lysophosphatidic acid (LPA) allowing us to identify NET1-dependent, LPA-dependent and NET1-mediated LPA-induced gene transcription. Differential gene expression was confirmed by quantitative PCR. Shortlisted NET1-dependent genes included STAT1, TSPAN1, TGFBi and CCL5 all of which were downregulatd upon NET1 downregulation. Shortlisted LPA-dependent genes included EGFR and PPARD where EGFR was upregulated and PPARD was downregulated upon LPA stimulation. Shortlisted NET1 and LPA dependent genes included IGFR1 and PIP5K3. These LPA induced genes were

  10. A functional and transcriptomic analysis of NET1 bioactivity in gastric cancer

    International Nuclear Information System (INIS)

    Bennett, Gayle; Sadlier, Denise; Doran, Peter P; MacMathuna, Padraic; Murray, David W

    2011-01-01

    NET1, a RhoA guanine exchange factor, is up-regulated in gastric cancer (GC) tissue and drives the invasive phenotype of this disease. In this study, we aimed to determine the role of NET1 in GC by monitoring the proliferation, motility and invasion of GC cells in which NET1 has been stably knocked down. Additionally, we aimed to determine NET1-dependent transcriptomic events that occur in GC. An in vitro model of stable knockdown of NET1 was achieved in AGS human gastric adenocarcinoma cells via lentiviral mediated transduction of short-hairpin (sh) RNA targeting NET1. Knockdown was assessed using quantitative PCR. Cell proliferation was assessed using an MTS assay and cell migration was assessed using a wound healing scratch assay. Cell invasion was assessed using a transwell matrigel invasion assay. Gene expression profiles were examined using affymetrix oligonucleotide U133A expression arrays. A student's t test was used to determine changes of statistical significance. GC cells were transduced with NET1 shRNA resulting in a 97% reduction in NET1 mRNA (p < 0.0001). NET1 knockdown significantly reduced the invasion and migration of GC cells by 94% (p < 0.05) and 24% (p < 0.001) respectively, while cell proliferation was not significantly altered following NET1 knockdown. Microarray analysis was performed on non-target and knockdown cell lines, treated with and without 10 μM lysophosphatidic acid (LPA) allowing us to identify NET1-dependent, LPA-dependent and NET1-mediated LPA-induced gene transcription. Differential gene expression was confirmed by quantitative PCR. Shortlisted NET1-dependent genes included STAT1, TSPAN1, TGFBi and CCL5 all of which were downregulatd upon NET1 downregulation. Shortlisted LPA-dependent genes included EGFR and PPARD where EGFR was upregulated and PPARD was downregulated upon LPA stimulation. Shortlisted NET1 and LPA dependent genes included IGFR1 and PIP5K3. These LPA induced genes were downregulated in NET1 knockdown cells

  11. The integrative epigenomic-transcriptomic landscape of ER positive breast cancer.

    Science.gov (United States)

    Gao, Yang; Jones, Allison; Fasching, Peter A; Ruebner, Matthias; Beckmann, Matthias W; Widschwendter, Martin; Teschendorff, Andrew E

    2015-01-01

    While recent integrative analyses of copy number and gene expression data in breast cancer have revealed a complex molecular landscape with multiple subtypes and many oncogenic/tumour suppressor driver events, much less is known about the role of DNA methylation in shaping breast cancer taxonomy and defining driver events. Here, we applied a powerful integrative network algorithm to matched DNA methylation and RNA-Seq data for 724 estrogen receptor (ER)-positive (ER+) breast cancers and 111 normal adjacent tissue specimens from The Cancer Genome Atlas (TCGA) project, in order to identify putative epigenetic driver events and to explore the resulting molecular taxonomy. This revealed the existence of nine functionally deregulated epigenetic hotspots encompassing a total of 146 genes, which we were able to validate in independent data sets encompassing over 1000 ER+ breast cancers. Integrative clustering of the matched messenger RNA (mRNA) and DNA methylation data over these genes resulted in only two clusters, which correlated very strongly with the luminal-A and luminal B subtypes. Overall, luminal-A and luminal-B breast cancers shared the same epigenetically deregulated hotspots but with luminal-B cancers exhibiting increased aberrant DNA methylation patterns relative to normal tissue. We show that increased levels of DNA methylation and mRNA expression deviation from the normal state define a marker of poor prognosis. Our data further implicates epigenetic silencing of WNT signalling antagonists and bone morphogenetic proteins (BMP) as key events underlying both luminal subtypes but specially of luminal-B breast cancer. Finally, we show that DNA methylation changes within the identified epigenetic interactome hotspots do not exhibit mutually exclusive patterns within the same cancer sample, instead exhibiting coordinated changes within the sample. Our results indicate that the integrative DNA methylation and transcriptomic landscape of ER+ breast cancer is

  12. Transcriptome profiling of the cancer, adjacent non-tumor and distant normal tissues from a colorectal cancer patient by deep sequencing.

    Directory of Open Access Journals (Sweden)

    Yan'an Wu

    Full Text Available Colorectal cancer (CRC is one of the most commonly diagnosed cancers in the world. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into the molecular basis of CRC initiation and progression. Compared with microarray technology, which is commonly used to identify transcriptional changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing, novel transcripts or gene fusion. In this study, we performed high-throughput transcriptome sequencing at ~50× coverage on CRC, adjacent non-tumor and distant normal tissue. The results revealed cancer-specific, differentially expressed genes and differential alternative splicing, suggesting that the extracellular matrix and metabolic pathways are activated and the genes related to cell homeostasis are suppressed in CRC. In addition, one tumor-restricted gene fusion, PRTEN-NOTCH2, was also detected and experimentally confirmed. This study reveals some common features in tumor invasion and provides a comprehensive survey of the CRC transcriptome, which provides better insight into the complexity of regulatory changes during tumorigenesis.

  13. Gene expression relationship between prostate cancer cells of Gleason 3, 4 and normal epithelial cells as revealed by cell type-specific transcriptomes

    International Nuclear Information System (INIS)

    Pascal, Laura E; Liu, Alvin Y; Vêncio, Ricardo ZN; Page, Laura S; Liebeskind, Emily S; Shadle, Christina P; Troisch, Pamela; Marzolf, Bruz; True, Lawrence D; Hood, Leroy E

    2009-01-01

    Prostate cancer cells in primary tumors have been typed CD10 - /CD13 - /CD24 hi /CD26 + /CD38 lo /CD44 - /CD104 - . This CD phenotype suggests a lineage relationship between cancer cells and luminal cells. The Gleason grade of tumors is a descriptive of tumor glandular differentiation. Higher Gleason scores are associated with treatment failure. CD26 + cancer cells were isolated from Gleason 3+3 (G3) and Gleason 4+4 (G4) tumors by cell sorting, and their gene expression or transcriptome was determined by Affymetrix DNA array analysis. Dataset analysis was used to determine gene expression similarities and differences between G3 and G4 as well as to prostate cancer cell lines and histologically normal prostate luminal cells. The G3 and G4 transcriptomes were compared to those of prostatic cell types of non-cancer, which included luminal, basal, stromal fibromuscular, and endothelial. A principal components analysis of the various transcriptome datasets indicated a closer relationship between luminal and G3 than luminal and G4. Dataset comparison also showed that the cancer transcriptomes differed substantially from those of prostate cancer cell lines. Genes differentially expressed in cancer are potential biomarkers for cancer detection, and those differentially expressed between G3 and G4 are potential biomarkers for disease stratification given that G4 cancer is associated with poor outcomes. Differentially expressed genes likely contribute to the prostate cancer phenotype and constitute the signatures of these particular cancer cell types

  14. Reduction in expression of the benign AR transcriptome is a hallmark of localised prostate cancer progression.

    Science.gov (United States)

    Stuchbery, Ryan; Macintyre, Geoff; Cmero, Marek; Harewood, Laurence M; Peters, Justin S; Costello, Anthony J; Hovens, Christopher M; Corcoran, Niall M

    2016-05-24

    Despite the importance of androgen receptor (AR) signalling to prostate cancer development, little is known about how this signalling pathway changes with increasing grade and stage of the disease. To explore changes in the normal AR transcriptome in localised prostate cancer, and its relation to adverse pathological features and disease recurrence. Publically accessible human prostate cancer expression arrays as well as RNA sequencing data from the prostate TCGA. Tumour associated PSA and PSAD were calculated for a large cohort of men (n=1108) undergoing prostatectomy. We performed a meta-analysis of the expression of an androgen-regulated gene set across datasets using Oncomine. Differential expression of selected genes in the prostate TCGA database was probed using the edgeR Bioconductor package. Changes in tumour PSA density with stage and grade were assessed by Student's t-test, and its association with biochemical recurrence explored by Kaplan-Meier curves and Cox regression. Meta-analysis revealed a systematic decline in the expression of a previously identified benign prostate androgen-regulated gene set with increasing tumour grade, reaching significance in nine of 25 genes tested despite increasing AR expression. These results were confirmed in a large independent dataset from the TCGA. At the protein level, when serum PSA was corrected for tumour volume, significantly lower levels were observed with increasing tumour grade and stage, and predicted disease recurrence. Lower PSA secretion-per-tumour-volume is associated with increasing grade and stage of prostate cancer, has prognostic relevance, and reflects a systematic perturbation of androgen signalling.

  15. Low dose irradiation reduces cancer mortality rates

    International Nuclear Information System (INIS)

    Luckey, T.D.

    2000-01-01

    Low doses of ionizing radiation stimulate development, growth, memory, sensual acuity, fecundity, and immunity (Luckey, T.D., ''Radiation Hormesis'', CRC Press, 1991). Increased immune competence reduces cancer mortality rates and provides increased average lifespan in animals. Decreased cancer mortality rates in atom bomb victims who received low dose irradiation makes it desirable to examine populations exposed to low dose irradiation. Studies with over 300,000 workers and 7 million person-years provide a valid comparison of radiation exposed and control unclear workers (Luckey, T.D., Nurture with Ionizing Radiation, Nutrition and Cancer, 34:1-11, 1999). Careful selection of controls eliminated any ''healthy worker effect''. The person-year corrected average indicated the cancer mortality rate of exposed workers was only 51% that of control workers. Lung cancer mortality rates showed a highly significant negative correlation with radon concentrations in 272,000 U.S. homes (Cohen, B.L., Health Physics 68:157-174, 1995). In contrast, radon concentrations showed no effect on lung cancer rates in miners from different countries (Lubin, J.H. Am. J. Epidemiology 140:323-332, 1994). This provides evidence that excessive lung cancer in miners is caused by particulates (the major factor) or toxic gases. The relative risk for cancer mortality was 3.7% in 10,000 Taiwanese exposed to low level of radiation from 60 Co in their steel supported homes (Luan, Y.C. et al., Am. Nuclear Soc. Trans. Boston, 1999). This remarkable finding needs further study. A major mechanism for reduced cancer mortality rates is increased immune competence; this includes both cell and humoral components. Low dose irradiation increases circulating lymphocytes. Macrophage and ''natural killer'' cells can destroy altered (cancer) cells before the mass becomes too large. Low dose irradiation also kills suppressor T-cells; this allows helper T-cells to activate killer cells and antibody producing cells

  16. Statin use and reduced cancer-related mortality

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Nordestgaard, Børge G; Bojesen, Stig E

    2012-01-01

    A reduction in the availability of cholesterol may limit the cellular proliferation required for cancer growth and metastasis. We tested the hypothesis that statin use begun before a cancer diagnosis is associated with reduced cancer-related mortality.......A reduction in the availability of cholesterol may limit the cellular proliferation required for cancer growth and metastasis. We tested the hypothesis that statin use begun before a cancer diagnosis is associated with reduced cancer-related mortality....

  17. In vitro downregulated hypoxia transcriptome is associated with poor prognosis in breast cancer.

    Science.gov (United States)

    Abu-Jamous, Basel; Buffa, Francesca M; Harris, Adrian L; Nandi, Asoke K

    2017-06-15

    Hypoxia is a characteristic of breast tumours indicating poor prognosis. Based on the assumption that those genes which are up-regulated under hypoxia in cell-lines are expected to be predictors of poor prognosis in clinical data, many signatures of poor prognosis were identified. However, it was observed that cell line data do not always concur with clinical data, and therefore conclusions from cell line analysis should be considered with caution. As many transcriptomic cell-line datasets from hypoxia related contexts are available, integrative approaches which investigate these datasets collectively, while not ignoring clinical data, are required. We analyse sixteen heterogeneous breast cancer cell-line transcriptomic datasets in hypoxia-related conditions collectively by employing the unique capabilities of the method, UNCLES, which integrates clustering results from multiple datasets and can address questions that cannot be answered by existing methods. This has been demonstrated by comparison with the state-of-the-art iCluster method. From this collection of genome-wide datasets include 15,588 genes, UNCLES identified a relatively high number of genes (>1000 overall) which are consistently co-regulated over all of the datasets, and some of which are still poorly understood and represent new potential HIF targets, such as RSBN1 and KIAA0195. Two main, anti-correlated, clusters were identified; the first is enriched with MYC targets participating in growth and proliferation, while the other is enriched with HIF targets directly participating in the hypoxia response. Surprisingly, in six clinical datasets, some sub-clusters of growth genes are found consistently positively correlated with hypoxia response genes, unlike the observation in cell lines. Moreover, the ability to predict bad prognosis by a combined signature of one sub-cluster of growth genes and one sub-cluster of hypoxia-induced genes appears to be comparable and perhaps greater than that of known

  18. Breast Cancer Detection with Reduced Feature Set

    Directory of Open Access Journals (Sweden)

    Ahmet Mert

    2015-01-01

    Full Text Available This paper explores feature reduction properties of independent component analysis (ICA on breast cancer decision support system. Wisconsin diagnostic breast cancer (WDBC dataset is reduced to one-dimensional feature vector computing an independent component (IC. The original data with 30 features and reduced one feature (IC are used to evaluate diagnostic accuracy of the classifiers such as k-nearest neighbor (k-NN, artificial neural network (ANN, radial basis function neural network (RBFNN, and support vector machine (SVM. The comparison of the proposed classification using the IC with original feature set is also tested on different validation (5/10-fold cross-validations and partitioning (20%–40% methods. These classifiers are evaluated how to effectively categorize tumors as benign and malignant in terms of specificity, sensitivity, accuracy, F-score, Youden’s index, discriminant power, and the receiver operating characteristic (ROC curve with its criterion values including area under curve (AUC and 95% confidential interval (CI. This represents an improvement in diagnostic decision support system, while reducing computational complexity.

  19. Transcriptome analysis of recurrently deregulated genes across multiple cancers identifies new pan-cancer biomarkers

    DEFF Research Database (Denmark)

    Kaczkowski, Bogumil; Tanaka, Yuji; Kawaji, Hideya

    2016-01-01

    Genes that are commonly deregulated in cancer are clinically attractive as candidate pan-diagnostic markers and therapeutic targets. To globally identify such targets, we compared Cap Analysis of Gene Expression (CAGE) profiles from 225 different cancer cell lines and 339 corresponding primary cell...

  20. Transcriptomic changes in human breast cancer progression as determined by serial analysis of gene expression

    International Nuclear Information System (INIS)

    Abba, Martin C; Aldaz, C Marcelo; Drake, Jeffrey A; Hawkins, Kathleen A; Hu, Yuhui; Sun, Hongxia; Notcovich, Cintia; Gaddis, Sally; Sahin, Aysegul; Baggerly, Keith

    2004-01-01

    Genomic and transcriptomic alterations affecting key cellular processes such us cell proliferation, differentiation and genomic stability are considered crucial for the development and progression of cancer. Most invasive breast carcinomas are known to derive from precursor in situ lesions. It is proposed that major global expression abnormalities occur in the transition from normal to premalignant stages and further progression to invasive stages. Serial analysis of gene expression (SAGE) was employed to generate a comprehensive global gene expression profile of the major changes occurring during breast cancer malignant evolution. In the present study we combined various normal and tumor SAGE libraries available in the public domain with sets of breast cancer SAGE libraries recently generated and sequenced in our laboratory. A recently developed modified t test was used to detect the genes differentially expressed. We accumulated a total of approximately 1.7 million breast tissue-specific SAGE tags and monitored the behavior of more than 25,157 genes during early breast carcinogenesis. We detected 52 transcripts commonly deregulated across the board when comparing normal tissue with ductal carcinoma in situ, and 149 transcripts when comparing ductal carcinoma in situ with invasive ductal carcinoma (P < 0.01). A major novelty of our study was the use of a statistical method that correctly accounts for the intra-SAGE and inter-SAGE library sources of variation. The most useful result of applying this modified t statistics beta binomial test is the identification of genes and gene families commonly deregulated across samples within each specific stage in the transition from normal to preinvasive and invasive stages of breast cancer development. Most of the gene expression abnormalities detected at the in situ stage were related to specific genes in charge of regulating the proper homeostasis between cell death and cell proliferation. The comparison of in situ lesions

  1. Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein

    NARCIS (Netherlands)

    Sotoca Covaleda, A.M.; Sollewijn Gelpke, M.D.; Boeren, S.; Ström, A.; Gustafsson, J.A.; Murk, A.J.; Rietjens, I.M.C.M.; Vervoort, J.J.M.

    2011-01-01

    The present study addresses, by transcriptomics and quantitative SILAC-based proteomics, the estrogen receptor alpha (ER) and beta (ERß)-mediated effects on gene and protein expression in T47D breast cancer cells exposed to the phytoestrogen genistein. Using the T47D human breast cancer cell line

  2. Systematic Identification and Assessment of Therapeutic Targets for Breast Cancer Based on Genome-Wide RNA Interference Transcriptomes

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2017-02-01

    Full Text Available With accumulating public omics data, great efforts have been made to characterize the genetic heterogeneity of breast cancer. However, identifying novel targets and selecting the best from the sizeable lists of candidate targets is still a key challenge for targeted therapy, largely owing to the lack of economical, efficient and systematic discovery and assessment to prioritize potential therapeutic targets. Here, we describe an approach that combines the computational evaluation and objective, multifaceted assessment to systematically identify and prioritize targets for biological validation and therapeutic exploration. We first establish the reference gene expression profiles from breast cancer cell line MCF7 upon genome-wide RNA interference (RNAi of a total of 3689 genes, and the breast cancer query signatures using RNA-seq data generated from tissue samples of clinical breast cancer patients in the Cancer Genome Atlas (TCGA. Based on gene set enrichment analysis, we identified a set of 510 genes that when knocked down could significantly reverse the transcriptome of breast cancer state. We then perform multifaceted assessment to analyze the gene set to prioritize potential targets for gene therapy. We also propose drug repurposing opportunities and identify potentially druggable proteins that have been poorly explored with regard to the discovery of small-molecule modulators. Finally, we obtained a small list of candidate therapeutic targets for four major breast cancer subtypes, i.e., luminal A, luminal B, HER2+ and triple negative breast cancer. This RNAi transcriptome-based approach can be a helpful paradigm for relevant researches to identify and prioritize candidate targets for experimental validation.

  3. Reducing the Burden of Cancer in East Africa

    Science.gov (United States)

    The mission of CGH is to advance global cancer research, build expertise, and leverage resources across nations to reduce cancer deaths worldwide. To carry out that mission, we facilitate the sharing of knowledge and expertise. CGH's latest effort, the East Africa Cancer Control Leadership Forum, carried out this mission by helping African partners develop their own individual cancer control programs.

  4. Drug Reduces Cancer Treatment-Related Joint Pain

    Science.gov (United States)

    A Cancer Currents blog post about a clinical trial demonstrating that duloxetine (Cymbalta®) may reduce joint pain caused by aromatase inhibitors in women being treated for early-stage breast cancer.

  5. Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Sylvie Maubant

    Full Text Available The canonical Wnt/β-catenin pathway is activated in triple-negative breast cancer (TNBC. The activation of this pathway leads to the expression of specific target genes depending on the cell/tissue context. Here, we analyzed the transcriptome of two different TNBC cell lines to define a comprehensive list of Wnt target genes. The treatment of cells with Wnt3a for 6h up-regulated the expression (fold change > 1.3 of 59 genes in MDA-MB-468 cells and 241 genes in HCC38 cells. Thirty genes were common to both cell lines. Beta-catenin may also be a transcriptional repressor and we found that 18 and 166 genes were down-regulated in response to Wnt3a treatment for 6h in MDA-MB-468 and HCC38 cells, respectively, of which six were common to both cell lines. Only half of the activated and the repressed transcripts have been previously described as Wnt target genes. Therefore, our study reveals 137 novel genes that may be positively regulated by Wnt3a and 104 novel genes that may be negatively regulated by Wnt3a. These genes are involved in the Wnt pathway itself, and also in TGFβ, p53 and Hedgehog pathways. Thorough characterization of these novel potential Wnt target genes may reveal new regulators of the canonical Wnt pathway. The comparison of our list of Wnt target genes with those published in other cellular contexts confirms the notion that Wnt target genes are tissue-, cell line- and treatment-specific. Genes up-regulated in Wnt3a-stimulated cell lines were more strongly expressed in TNBC than in luminal A breast cancer samples. These genes were also overexpressed, but to a much lesser extent, in HER2+ and luminal B tumors. We identified 72 Wnt target genes higher expressed in TNBCs (17 with a fold change >1.3 which may reflect the chronic activation of the canonical Wnt pathway that occurs in TNBC tumors.

  6. Transcriptome-wide studies of prostate cancer cell lines in the context of medical radiation

    International Nuclear Information System (INIS)

    Hammer, Paul

    2012-01-01

    The use of radiotherapy in addition to chemotherapy and surgical removal is the most powerful instrument in the fight against malignant tumors in cancer medicine. After cardiovascular diseases, cancer is the second leading cause of death in the western world, in which prostate cancer is the most frequent male cancer. Despite continuous technological improvements in radiological instruments and prognosis, it may occur a recurrence up to many years after radiotherapy due to a high resistance capability of individual malignant cells of the locally occurring tumor. Although modern radiation biology has studied many aspects of the resistance mechanisms, questions are largely unanswered especially in regards to prognostic terms and time response of tumor cells to ionizing radiation. As cellular models four prostate cancer cell lines with different radiation sensitivities (PC3, DuCaP, DU-145, RWPE-1) were cultured and tested for their ability to survive after exposure to ionizing radiation by a trypane blue and MTT viability assay. The proliferative capacity of the four cell lines was determined using a colony formation assay. The PC3 cell line (radiation-resistant) and the DuCaP cell line (radiation-sensitive) showed the maximal differences in terms of radiation sensitivity. Based on these results the two cell lines were selected to allow identification of potential prognostic marker for predicting the effectiveness of radiation therapy via their transcriptome-wide gene expression. Furthermore, a time series experiment with the radiation-resistant PC3 cell line was performed. At 8 different time points, during the period from 00:00 - 42:53 (hh:mm) after exposure with 1 Gy, the mRNA was quantified by next generation sequencing to investigate the dynamic behavior of time-delayed gene expression and to discover resistance mechanisms. Of 10,966 expressed genes 730 were significant differentially expressed, determined by setting a fold change threshold in conjunction with a P

  7. Reduced male fertility in childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Sun Hee Lee

    2013-12-01

    Full Text Available With advances in cancer treatment, more pediatric cancer patients have increased their life expectancy. Because cancer-related therapy causes various physical and psychological problems, many male survivors experience later problems with thyroid and sexual functions, and with growth. As outcomes have improved, more survivors need to maintain their reproductive function to maximize their long-term quality of life. Cancer and cancer-related treatment can impair fertility by damage to the testes, to the hypothalamic-pituitary-gonadal axis, or to the genitourinary organs. Prior radiation therapy to the testes, the use of alkylating agents, and central hypogonadism further impair fertility in male survivors of childhood cancer. Following any course of chemotherapy, peripubertal maturation, any testicular volume changes, and symptoms of androgen deficiency should be monitored systematically. If patients request fertility testing, spermatogenesis status can be evaluated either directly by semen analysis or indirectly by determination of the levels of testosterone/gonadotropins and by monitoring any changes in testicular volume. According to the patient's condition, semen cryopreservation, hormonal therapy, or assisted reproduction technologies should be provided.

  8. Molecular portrait of breast cancer in China reveals comprehensive transcriptomic likeness to Caucasian breast cancer and low prevalence of luminal A subtype

    International Nuclear Information System (INIS)

    Huang, Xiaoyan; Dugo, Matteo; Callari, Maurizio; Sandri, Marco; De Cecco, Loris; Valeri, Barbara; Carcangiu, Maria Luisa; Xue, Jingyan; Bi, Rui; Veneroni, Silvia; Daidone, Maria Grazia; Ménard, Sylvie; Tagliabue, Elda; Shao, Zhimin; Wu, Jiong; Orlandi, Rosaria

    2015-01-01

    The recent dramatic increase in breast cancer incidence across China with progressive urbanization and economic development has signaled the urgent need for molecular and clinical detailing of breast cancer in the Chinese population. Our analyses of a unique transethnic collection of breast cancer frozen specimens from Shanghai Fudan Cancer Center (Chinese Han) profiled simultaneously with an analogous Caucasian Italian series revealed consistent transcriptomic data lacking in batch effects. The prevalence of Luminal A subtype was significantly lower in Chinese series, impacting the overall prevalence of estrogen receptor (ER)-positive disease in a large cohort of Chinese/Caucasian patients. Unsupervised and supervised comparison of gene and microRNA (miRNA) profiles of Chinese and Caucasian samples revealed extensive similarity in the comprehensive taxonomy of transcriptional elements regulating breast cancer biology. Partition of gene expression data using gene lists relevant to breast cancer as “intrinsic” and “extracellular matrix” genes identified Chinese and Caucasian subgroups with equivalent global gene and miRNA profiles. These findings indicate that in the Chinese and Caucasian groups, breast neoplasia and the surrounding stromal characteristics undergo the same differentiation and molecular processes. Transcriptional similarity across transethnic cohorts may simplify translational medicine approaches and clinical management of breast cancer patients worldwide

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

    Directory of Open Access Journals (Sweden)

    Arindam Datta

    2016-06-01

    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.

  10. Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study

    Science.gov (United States)

    Ross-Adams, H.; Lamb, A.D.; Dunning, M.J.; Halim, S.; Lindberg, J.; Massie, C.M.; Egevad, L.A.; Russell, R.; Ramos-Montoya, A.; Vowler, S.L.; Sharma, N.L.; Kay, J.; Whitaker, H.; Clark, J.; Hurst, R.; Gnanapragasam, V.J.; Shah, N.C.; Warren, A.Y.; Cooper, C.S.; Lynch, A.G.; Stark, R.; Mills, I.G.; Grönberg, H.; Neal, D.E.

    2015-01-01

    Background Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. Methods In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. Findings We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene

  11. Reducing cancer risk in rural communities through supermarket interventions.

    Science.gov (United States)

    McCool, Barent N; Lyford, Conrad P; Hensarling, Natalie; Pence, Barbara; McCool, Audrey C; Thapa, Janani; Belasco, Eric; Carter, Tyra M

    2013-09-01

    Cancer risk is high, and prevention efforts are often minimal in rural communities. Feasible means of encouraging lifestyles that will reduce cancer risk for residents of rural communities are needed. This project developed and tested a model that could be feasibly adopted by rural communities to reduce cancer risk. This model focuses on incorporating multi-faceted cancer risk education in the local supermarket. As the supermarket functions both as the primary food source and an information source in small rural communities, the supermarket focus encourages the development of a community environment supportive of lifestyles that should reduce residents' risk for cancer. The actions taken to implement the model and the challenges that communities would have in implementing the model are identified.

  12. Aging Impacts Transcriptome but not Genome of Hormone-dependentBreast Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Yau, Christina; Fedele, Vita; Roydasgupta, Ritu; Fridlyand, Jane; Hubbard, Alan; Gray, Joe W.; Chew, Karen; Dairkee, Shanaz H.; Moore, DanH.; Schittulli, Francesco; Tommasi, Stefania; Paradiso, Angelo; Albertson, Donna G.; Benz, Christopher C.

    2007-10-09

    Age is one of the most important risk factors for human malignancies, including breast cancer; in addition, age-at-diagnosis has been shown to be an independent indicator of breast cancer prognosis. However, except for inherited forms of breast cancer, there is little genetic or epigenetic understanding of the biological basis linking aging with sporadic breast cancer incidence and its clinical behavior.

  13. A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer

    International Nuclear Information System (INIS)

    Meyniel, Jean-Philippe; Alran, Séverine; Rapinat, Audrey; Gentien, David; Roman-Roman, Sergio; Mignot, Laurent; Sastre-Garau, Xavier; Cottu, Paul H; Decraene, Charles; Stern, Marc-Henri; Couturier, Jérôme; Lebigot, Ingrid; Nicolas, André; Weber, Nina; Fourchotte, Virginie

    2010-01-01

    The distinction between primary and secondary ovarian tumors may be challenging for pathologists. The purpose of the present work was to develop genomic and transcriptomic tools to further refine the pathological diagnosis of ovarian tumors after a previous history of breast cancer. Sixteen paired breast-ovary tumors from patients with a former diagnosis of breast cancer were collected. The genomic profiles of paired tumors were analyzed using the Affymetrix GeneChip ® Mapping 50 K Xba Array or Genome-Wide Human SNP Array 6.0 (for one pair), and the data were normalized with ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) algorithm or Partek Genomic Suite, respectively. The transcriptome of paired samples was analyzed using Affymetrix GeneChip ® Human Genome U133 Plus 2.0 Arrays, and the data were normalized with gc-Robust Multi-array Average (gcRMA) algorithm. A hierarchical clustering of these samples was performed, combined with a dataset of well-identified primary and secondary ovarian tumors. In 12 of the 16 paired tumors analyzed, the comparison of genomic profiles confirmed the pathological diagnosis of primary ovarian tumor (n = 5) or metastasis of breast cancer (n = 7). Among four cases with uncertain pathological diagnosis, genomic profiles were clearly distinct between the ovarian and breast tumors in two pairs, thus indicating primary ovarian carcinomas, and showed common patterns in the two others, indicating metastases from breast cancer. In all pairs, the result of the transcriptomic analysis was concordant with that of the genomic analysis. In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors. Transcriptomic analysis may be used when primary breast tissue specimen is not available

  14. Breast cancer after bilateral risk-reducing mastectomy

    DEFF Research Database (Denmark)

    Skytte, A-B; Crüger, Dorthe Gylling; Gerster, M

    2011-01-01

    This study aims to evaluate the incidence of breast cancer after risk-reducing mastectomy (RRM) in healthy BRCA mutation carriers. This study is a long-term follow-up of 307 BRCA mutation carriers of whom 96 chose RRM. None of the study participants had a previous history of breast or ovarian...... cancer nor had they undergone RRM or risk-reducing bilateral salpingo-oophorectomy (BSO) prior to the time of BRCA testing. The annual incidence of post-mastectomy breast cancer was 0.8% compared with 1.7% in the non-operated group. Implications of these findings in relation to genetic counseling...

  15. Proton irradiation impacts age-driven modulations of cancer progression influenced by immune system transcriptome modifications from splenic tissue

    International Nuclear Information System (INIS)

    Wage, Justin; Ma, Lili; Peluso, Michael; Lamont, Clare; Hahnfeldt, Philip; Hlatky, Lynn; Beheshti, Afshin; Evens, Andrew M.

    2015-01-01

    Age plays a crucial role in the interplay between tumor and host, with additional impact due to irradiation. Proton irradiation of tumors induces biological modulations including inhibition of angiogenic and immune factors critical to 'hallmark' processes impacting tumor development. Proton irradiation has also provided promising results for proton therapy in cancer due to targeting advantages. Additionally, protons may contribute to the carcinogenesis risk from space travel (due to the high proportion of high-energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice was altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68-day) versus old (736-day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5 Gy (1-GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared with older subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74 and RUVBL2 indicated these were the key genes involved in the regulatory changes in the host environment response (i.e. the spleen). Collectively, these results suggest that a significant biological component of proton irradiation is modulated by host age through promotion of carcinogenesis in adolescence and resistance to immunosuppression, carcinogenesis and genetic perturbation associated with advancing age. (author)

  16. Transcriptome Profiling of Caco-2 Cancer Cell Line following Treatment with Extracts from Iodine-Biofortified Lettuce (Lactuca sativa L..

    Directory of Open Access Journals (Sweden)

    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.

  17. A collection of annotated and harmonized human breast cancer transcriptome datasets, including immunologic classification [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Jessica Roelands

    2018-02-01

    Full Text Available The increased application of high-throughput approaches in translational research has expanded the number of publicly available data repositories. Gathering additional valuable information contained in the datasets represents a crucial opportunity in the biomedical field. To facilitate and stimulate utilization of these datasets, we have recently developed an interactive data browsing and visualization web application, the Gene Expression Browser (GXB. In this note, we describe a curated compendium of 13 public datasets on human breast cancer, representing a total of 2142 transcriptome profiles. We classified the samples according to different immune based classification systems and integrated this information into the datasets. Annotated and harmonized datasets were uploaded to GXB. Study samples were categorized in different groups based on their immunologic tumor response profiles, intrinsic molecular subtypes and multiple clinical parameters. Ranked gene lists were generated based on relevant group comparisons. In this data note, we demonstrate the utility of GXB to evaluate the expression of a gene of interest, find differential gene expression between groups and investigate potential associations between variables with a specific focus on immunologic classification in breast cancer. This interactive resource is publicly available online at: http://breastcancer.gxbsidra.org/dm3/geneBrowser/list.

  18. Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.

    Science.gov (United States)

    Michaut, Magali; Chin, Suet-Feung; Majewski, Ian; Severson, Tesa M; Bismeijer, Tycho; de Koning, Leanne; Peeters, Justine K; Schouten, Philip C; Rueda, Oscar M; Bosma, Astrid J; Tarrant, Finbarr; Fan, Yue; He, Beilei; Xue, Zheng; Mittempergher, Lorenza; Kluin, Roelof J C; Heijmans, Jeroen; Snel, Mireille; Pereira, Bernard; Schlicker, Andreas; Provenzano, Elena; Ali, Hamid Raza; Gaber, Alexander; O'Hurley, Gillian; Lehn, Sophie; Muris, Jettie J F; Wesseling, Jelle; Kay, Elaine; Sammut, Stephen John; Bardwell, Helen A; Barbet, Aurélie S; Bard, Floriane; Lecerf, Caroline; O'Connor, Darran P; Vis, Daniël J; Benes, Cyril H; McDermott, Ultan; Garnett, Mathew J; Simon, Iris M; Jirström, Karin; Dubois, Thierry; Linn, Sabine C; Gallagher, William M; Wessels, Lodewyk F A; Caldas, Carlos; Bernards, Rene

    2016-01-05

    Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.

  19. Reduced cancer risk in vegetarians: an analysis of recent reports

    Directory of Open Access Journals (Sweden)

    Amy Joy Lanou

    2010-12-01

    Full Text Available Amy Joy Lanou1, Barbara Svenson21Department of Health and Wellness, 2Ramsey Library, University of North Carolina Asheville, Asheville, NC, USAAbstract: This report reviews current evidence regarding the relationship between vegetarian eating patterns and cancer risk. Although plant-based diets including vegetarian and vegan diets are generally considered to be cancer protective, very few studies have directly addressed this question. Most large prospective observational studies show that vegetarian diets are at least modestly cancer protective (10%–12% reduction in overall cancer risk although results for specific cancers are less clear. No long-term randomized clinical trials have been conducted to address this relationship. However, a broad body of evidence links specific plant foods such as fruits and vegetables, plant constituents such as fiber, antioxidants and other phytochemicals, and achieving and maintaining a healthy weight to reduced risk of cancer diagnosis and recurrence. Also, research links the consumption of meat, especially red and processed meats, to increased risk of several types of cancer. Vegetarian and vegan diets increase beneficial plant foods and plant constituents, eliminate the intake of red and processed meat, and aid in achieving and maintaining a healthy weight. The direct and indirect evidence taken together suggests that vegetarian diets are a useful strategy for reducing risk of cancer.Keywords: diet, vegan, prevention

  20. Reduced cancer risk in vegetarians: an analysis of recent reports.

    Science.gov (United States)

    Lanou, Amy Joy; Svenson, Barbara

    2010-12-20

    This report reviews current evidence regarding the relationship between vegetarian eating patterns and cancer risk. Although plant-based diets including vegetarian and vegan diets are generally considered to be cancer protective, very few studies have directly addressed this question. Most large prospective observational studies show that vegetarian diets are at least modestly cancer protective (10%-12% reduction in overall cancer risk) although results for specific cancers are less clear. No long-term randomized clinical trials have been conducted to address this relationship. However, a broad body of evidence links specific plant foods such as fruits and vegetables, plant constituents such as fiber, antioxidants and other phytochemicals, and achieving and maintaining a healthy weight to reduced risk of cancer diagnosis and recurrence. Also, research links the consumption of meat, especially red and processed meats, to increased risk of several types of cancer. Vegetarian and vegan diets increase beneficial plant foods and plant constituents, eliminate the intake of red and processed meat, and aid in achieving and maintaining a healthy weight. The direct and indirect evidence taken together suggests that vegetarian diets are a useful strategy for reducing risk of cancer.

  1. Ovarian and Breast Cancer Spheres Are Similar in Transcriptomic Features and Sensitive to Fenretinide

    Directory of Open Access Journals (Sweden)

    Haiwei Wang

    2013-01-01

    Full Text Available Cancer stem cells (CSCs are resistant to chemotherapy and are ability to regenerate cancer cell populations, thus attracting much attention in cancer research. In this report, we first demonstrated that sphere cells from ovarian cancer cell line A2780 shared many features of CSCs, such as resistance to cisplatin and able to initiate tumors in an efficient manner. Then, we conducted cDNA microarray analysis on spheres from ovarian A2780 cells, and from breast MCF7 and SUM159 cells, and found that molecular pathways underlying spheres from these cancer cell lines were similar to a large extent, suggesting that similar mechanisms are involved in the genesis of CSCs in both ovarian and breast cancer types. In addition, we showed that spheres from these cancer types were highly sensitive to fenretinide, a stimulus of oxidative stress-mediated apoptosis in cancer cells. Thus, our results not only provide important insights into mechanisms underlying CSCs in ovarian and breast cancer, but also lead to the development of more sophisticated protocols of cancer therapy in near future.

  2. Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival

    Science.gov (United States)

    ... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... Nearly 7,000 women with early-stage, estrogen receptor-positive breast cancer were enrolled in the trial ...

  3. Translating Research into Policy: Reducing Breast Cancer Disparities in Illinois

    Science.gov (United States)

    Dr. Carol Ferrans is internationally recognized for her work in disparities in health care and quality of life outcomes. She has a distinguished record of research that includes major grants funded by three institutes of the National Institutes of Health (National Cancer Institute, National Institute for Minority Health and Health Disparities, and National Institute for Nursing Research).    Dr. Ferrans’ work has been instrumental in reducing the disparity in breast cancer mortality Chicago, which at its peak was among the worst in the nation.  Efforts led by Dr. Ferrans and colleagues led directly to statewide legislation, to address the multifaceted causes of black/white disparity in deaths from breast cancer.  She was one of the founders of the Metropolitan Chicago Breast Cancer Task Force (MCBCTF), leading the team focusing on barriers to mammography screening, to identify reasons for the growing disparity in breast cancer mortality. Their findings (citing Ferrans’ research and others) and recommendations for action were translated directly into the Illinois Reducing Breast Cancer Disparities Act and two additional laws strengthening the Act.  These laws and other statewide efforts have improved access to screening and quality of mammography throughout the Illinois. In addition, Dr. Ferrans and her team identified cultural beliefs contributing to later stage diagnosis of breast cancer in African American and Latino women in Chicago, and most importantly, showed that these beliefs can be changed.  They reached more than 8,000 African American women in Chicago with a short film on DVD, which was effective in changing beliefs and promoting screening.  Her team’s published findings were cited by the American Cancer Society in their guidelines for breast cancer screening.  The Chicago black/white disparity in breast cancer deaths has decreased by 35% since the MCBCTF first released its report, according to data from the Illinois Department of Public

  4. Editor's Highlight: Transcriptome Profiling Reveals Bisphenol A Alternatives Activate Estrogen Receptor Alpha in Human Breast Cancer Cells.

    Science.gov (United States)

    Mesnage, Robin; Phedonos, Alexia; Arno, Matthew; Balu, Sucharitha; Corton, J Christopher; Antoniou, Michael N

    2017-08-01

    Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in "BPA-free" products. We have compared estrogenic activity of BPA with 6 bisphenol analogues [bisphenol S (BPS); bisphenol F (BPF); bisphenol AP (BPAP); bisphenol AF (BPAF); bisphenol Z (BPZ); bisphenol B (BPB)] in 3 human breast cancer cell lines. Estrogenicity was assessed (10-11-10-4 M) by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element-mediated transcription in a luciferase assay. BPAF was the most potent bisphenol, followed by BPB > BPZ ∼ BPA > BPF ∼ BPAP > BPS. The addition of ICI 182,780 antagonized the activation of ERs. Data mining of ToxCast high-throughput screening assays confirm our results but also show divergence in the sensitivities of the assays. Gene expression profiles were determined in MCF-7 cells by microarray analysis. The comparison of transcriptome profile alterations resulting from BPA alternatives with an ERα gene expression biomarker further indicates that all BPA alternatives act as ERα agonists in MCF-7 cells. These results were confirmed by Illumina-based RNA sequencing. In conclusion, BPA alternatives are not necessarily less estrogenic than BPA in human breast cancer cells. BPAF, BPB, and BPZ were more estrogenic than BPA. These findings point to the importance of better understanding the risk of adverse effects from exposure to BPA alternatives, including hormone-dependent breast cancer. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology.

  5. Assessment of Radiation Induced Therapeutic Effect and Cytotoxicity in Cancer Patients Based on Transcriptomic Profiling

    Directory of Open Access Journals (Sweden)

    Sajjad Karim

    2016-02-01

    Full Text Available Toxicity induced by radiation therapy is a curse for cancer patients undergoing treatment. It is imperative to understand and define an ideal condition where the positive effects notably outweigh the negative. We used a microarray meta-analysis approach to measure global gene-expression before and after radiation exposure. Bioinformatic tools were used for pathways, network, gene ontology and toxicity related studies. We found 429 differentially expressed genes at fold change >2 and p-value <0.05. The most significantly upregulated genes were synuclein alpha (SNCA, carbonic anhydrase I (CA1, X-linked Kx blood group (XK, glycophorin A and B (GYPA and GYPB, and hemogen (HEMGN, while downregulated ones were membrane-spanning 4-domains, subfamily A member 1 (MS4A1, immunoglobulin heavy constant mu (IGHM, chemokine (C-C motif receptor 7 (CCR7, BTB and CNC homology 1 transcription factor 2 (BACH2, and B-cell CLL/lymphoma 11B (BCL11B. Pathway analysis revealed calcium-induced T lymphocyte apoptosis and the role of nuclear factor of activated T-cells (NFAT in regulation of the immune response as the most inhibited pathways, while apoptosis signaling was significantly activated. Most of the normal biofunctions were significantly decreased while cell death and survival process were activated. Gene ontology enrichment analysis revealed the immune system process as the most overrepresented group under the biological process category. Toxicity function analysis identified liver, kidney and heart to be the most affected organs during and after radiation therapy. The identified biomarkers and alterations in molecular pathways induced by radiation therapy should be further investigated to reduce the cytotoxicity and development of fatigue.

  6. Periodontal disease with treatment reduces subsequent cancer risks.

    Science.gov (United States)

    Hwang, Ing-Ming; Sun, Li-Min; Lin, Cheng-Li; Lee, Chun-Feng; Kao, Chia-Hung

    2014-10-01

    The aim of our study was to evaluate the relationship between routine treatment of periodontal disease (PD) and the subsequent risks for cancers in Taiwan. Study participants were selected from the Taiwan National Health Insurance (NHI) system database. The PD with a routine treatment cohort contained 38 902 patients. For each treatment cohort participant, two age- and sex-matched comparison (control) cohort participants were randomly selected. Cox's proportional hazards regression analysis was used to estimate the effects of PD with treatment on the subsequent risk of cancer. The overall risk of developing cancer was significantly lower in the treatment cohort than in the patients without treatment (adjusted Hazard ratio = 0.72, 95% confidence interval = 0.68-0.76). The risks of developing most gastrointestinal tract, lung, gynecological and brain malignancies were significantly lower in the treatment cohort than in the comparison cohort. In contrast, the risks of prostate and thyroid cancers were significantly higher in the treatment cohort than in the comparison cohort. Our findings suggest that PD with treatment is associated with a significantly reduced overall risk of cancer and reduced risks of certain types of cancers. © The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Reducing Breast Cancer Recurrence: The Role of Dietary Polyphenolics

    Directory of Open Access Journals (Sweden)

    Andrea J. Braakhuis

    2016-09-01

    Full Text Available Evidence from numerous observational and clinical studies suggest that polyphenolic phytochemicals such as phenolic acids in olive oil, flavonols in tea, chocolate and grapes, and isoflavones in soy products reduce the risk of breast cancer. A dietary food pattern naturally rich in polyphenols is the Mediterranean diet and evidence suggests those of Mediterranean descent have a lower breast cancer incidence. Whilst dietary polyphenols have been the subject of breast cancer risk-reduction, this review will focus on the clinical effects of polyphenols on reducing recurrence. Overall, we recommend breast cancer patients consume a diet naturally high in flavonol polyphenols including tea, vegetables (onion, broccoli, and fruit (apples, citrus. At least five servings of vegetables and fruit daily appear protective. Moderate soy protein consumption (5–10 g daily and the Mediterranean dietary pattern show the most promise for breast cancer patients. In this review, we present an overview of clinical trials on supplementary polyphenols of dietary patterns rich in polyphenols on breast cancer recurrence, mechanistic data, and novel delivery systems currently being researched.

  8. Early molecular events involved in Pinus pinaster Ait. somatic embryo development under reduced water availability: transcriptomic and proteomic analyses.

    Science.gov (United States)

    Morel, Alexandre; Teyssier, Caroline; Trontin, Jean-François; Eliášová, Kateřina; Pešek, Bedřich; Beaufour, Martine; Morabito, Domenico; Boizot, Nathalie; Le Metté, Claire; Belal-Bessai, Leila; Reymond, Isabelle; Harvengt, Luc; Cadene, Martine; Corbineau, Françoise; Vágner, Martin; Label, Philippe; Lelu-Walter, Marie-Anne

    2014-09-01

    Maritime pine somatic embryos (SEs) require a reduction in water availability (high gellan gum concentration in the maturation medium) to reach the cotyledonary stage. This key switch, reported specifically for pine species, is not yet well understood. To facilitate the use of somatic embryogenesis for mass propagation of conifers, we need a better understanding of embryo development. Comparison of both transcriptome (Illumina RNA sequencing) and proteome [two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis with mass spectrometry (MS) identification] of immature SEs, cultured on either high (9G) or low (4G) gellan gum concentration, was performed, together with analysis of water content, fresh and dry mass, endogenous abscisic acid (ABA; gas chromatography-MS), soluble sugars (high-pressure liquid chromatography), starch and confocal laser microscope observations. This multiscale, integrated analysis was used to unravel early molecular and physiological events involved in SE development. Under unfavorable conditions (4G), the glycolytic pathway was enhanced, possibly in relation to cell proliferation that may be antagonistic to SE development. Under favorable conditions (9G), SEs adapted to culture constraint by activating specific protective pathways, and ABA-mediated molecular and physiological responses promoting embryo development. Our results suggest that on 9G, germin-like protein and ubiquitin-protein ligase could be used as predictive markers of SE development, whereas protein phosphatase 2C could be a biomarker for culture adaptive responses. This is the first characterization of early molecular mechanisms involved in the development of pine SEs following an increase in gellan gum concentration in the maturation medium, and it is also the first report on somatic embryogenesis in conifers combining transcriptomic and proteomic datasets. © 2014 Scandinavian Plant Physiology Society.

  9. Transcriptome and DNA Methylome Analysis in a Mouse Model of Diet-Induced Obesity Predicts Increased Risk of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Ruifang Li

    2018-01-01

    Full Text Available Colorectal cancer (CRC tends to occur at older age; however, CRC incidence rates have been rising sharply among young age groups. The increasing prevalence of obesity is recognized as a major risk, yet the mechanistic underpinnings remain poorly understood. Using a diet-induced obesity mouse model, we identified obesity-associated molecular changes in the colonic epithelium of young and aged mice, and we further investigated whether the changes were reversed after weight loss. Transcriptome analysis indicated that obesity-related colonic cellular metabolic switch favoring long-chain fatty acid oxidation happened in young mice, while obesity-associated downregulation of negative feedback regulators of pro-proliferative signaling pathways occurred in older mice. Strikingly, colonic DNA methylome was pre-programmed by obesity at young age, priming for a tumor-prone gene signature after aging. Furthermore, obesity-related changes were substantially preserved after short-term weight loss, but they were largely reversed after long-term weight loss. We provided mechanistic insights into increased CRC risk in obesity.

  10. Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer

    DEFF Research Database (Denmark)

    Martens-Uzunova, E S; Jalava, S E; Dits, N F

    2011-01-01

    Prostate cancer (PCa) is the most frequent male malignancy and the second most common cause of cancer-related death in Western countries. Current clinical and pathological methods are limited in the prediction of postoperative outcome. It is becoming increasingly evident that small non-coding RNA...... signatures of 102 fresh-frozen patient samples during PCa progression by miRNA microarrays. Both platforms were cross-validated by quantitative reverse transcriptase-PCR. Besides the altered expression of several miRNAs, our deep sequencing analyses revealed strong differential expression of small nucleolar...... RNAs (snoRNAs) and transfer RNAs (tRNAs). From microarray analysis, we derived a miRNA diagnostic classifier that accurately distinguishes normal from cancer samples. Furthermore, we were able to construct a PCa prognostic predictor that independently forecasts postoperative outcome. Importantly...

  11. Network-Based Isoform Quantification with RNA-Seq Data for Cancer Transcriptome Analysis.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2015-12-01

    Full Text Available High-throughput mRNA sequencing (RNA-Seq is widely used for transcript quantification of gene isoforms. Since RNA-Seq data alone is often not sufficient to accurately identify the read origins from the isoforms for quantification, we propose to explore protein domain-domain interactions as prior knowledge for integrative analysis with RNA-Seq data. We introduce a Network-based method for RNA-Seq-based Transcript Quantification (Net-RSTQ to integrate protein domain-domain interaction network with short read alignments for transcript abundance estimation. Based on our observation that the abundances of the neighboring isoforms by domain-domain interactions in the network are positively correlated, Net-RSTQ models the expression of the neighboring transcripts as Dirichlet priors on the likelihood of the observed read alignments against the transcripts in one gene. The transcript abundances of all the genes are then jointly estimated with alternating optimization of multiple EM problems. In simulation Net-RSTQ effectively improved isoform transcript quantifications when isoform co-expressions correlate with their interactions. qRT-PCR results on 25 multi-isoform genes in a stem cell line, an ovarian cancer cell line, and a breast cancer cell line also showed that Net-RSTQ estimated more consistent isoform proportions with RNA-Seq data. In the experiments on the RNA-Seq data in The Cancer Genome Atlas (TCGA, the transcript abundances estimated by Net-RSTQ are more informative for patient sample classification of ovarian cancer, breast cancer and lung cancer. All experimental results collectively support that Net-RSTQ is a promising approach for isoform quantification. Net-RSTQ toolbox is available at http://compbio.cs.umn.edu/Net-RSTQ/.

  12. Supervised exercise reduces cancer-related fatigue: a systematic review

    Directory of Open Access Journals (Sweden)

    José F Meneses-Echávez

    2015-01-01

    Full Text Available Question: Does supervised physical activity reduce cancer-related fatigue? Design: Systematic review with meta-analysis of randomised trials. Participants: People diagnosed with any type of cancer, without restriction to a particular stage of diagnosis or treatment. Intervention: Supervised physical activity interventions (eg, aerobic, resistance and stretching exercise, defined as any planned or structured body movement causing an increase in energy expenditure, designed to maintain or enhance health-related outcomes, and performed with systematic frequency, intensity and duration. Outcome measures: The primary outcome measure was fatigue. Secondary outcomes were physical and functional wellbeing assessed using the Functional Assessment of Cancer Therapy Fatigue Scale, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Piper Fatigue Scale, Schwartz Cancer Fatigue Scale and the Multidimensional Fatigue Inventory. Methodological quality, including risk of bias of the studies, was evaluated using the PEDro Scale. Results: Eleven studies involving 1530 participants were included in the review. The assessment of quality showed a mean score of 6.5 (SD 1.1, indicating a low overall risk of bias. The pooled effect on fatigue, calculated as a standardised mean difference (SMD using a random-effects model, was –1.69 (95% CI –2.99 to –0.39. Beneficial reductions in fatigue were also found with combined aerobic and resistance training with supervision (SMD = –0.41, 95% CI –0.70 to –0.13 and with combined aerobic, resistance and stretching training with supervision (SMD = –0.67, 95% CI –1.17 to –0.17. Conclusion: Supervised physical activity interventions reduce cancer-related fatigue. These findings suggest that combined aerobic and resistance exercise regimens with or without stretching should be included as part of rehabilitation programs for people who have been diagnosed with cancer

  13. Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes.

    Science.gov (United States)

    Dobroff, Andrey S; D'Angelo, Sara; Eckhardt, Bedrich L; Ferrara, Fortunato; Staquicini, Daniela I; Cardó-Vila, Marina; Staquicini, Fernanda I; Nunes, Diana N; Kim, Kisu; Driessen, Wouter H P; Hajitou, Amin; Lomo, Lesley C; Barry, Marc; Krishnamurthy, Savitri; Sahin, Aysegul; Woodward, Wendy A; Prossnitz, Eric R; Anderson, Robin L; Dias-Neto, Emmanuel; Brown-Glaberman, Ursa A; Royce, Melanie E; Ueno, Naoto T; Cristofanilli, Massimo; Hortobagyi, Gabriel N; Marchiò, Serena; Gelovani, Juri G; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2016-10-24

    Inflammatory breast carcinoma (IBC) is one of the most lethal forms of human breast cancer, and effective treatment for IBC is an unmet clinical need in contemporary oncology. Tumor-targeted theranostic approaches are emerging in precision medicine, but only a few specific biomarkers are available. Here we report up-regulation of the 78-kDa glucose-regulated protein (GRP78) in two independent discovery and validation sets of specimens derived from IBC patients, suggesting translational promise for clinical applications. We show that a GRP78-binding motif displayed on either bacteriophage or adeno-associated virus/phage (AAVP) particles or loop-grafted onto a human antibody fragment specifically targets orthotopic IBC and other aggressive breast cancer models in vivo. To evaluate the theranostic value, we used GRP78-targeting AAVP particles to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) transgene, obtaining simultaneous in vivo diagnosis through PET imaging and tumor treatment by selective activation of the prodrug ganciclovir at tumor sites. Translation of this AAVP system is expected simultaneously to image, monitor, and treat the IBC phenotype and possibly other aggressive (e.g., invasive and/or metastatic) subtypes of breast cancer, based on the inducible cell-surface expression of the stress-response chaperone GRP78, and possibily other cell-surface receptors in human tumors.

  14. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines.

    Directory of Open Access Journals (Sweden)

    Marilyn Carrier

    Full Text Available Retinoic acid (RA, the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome". Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα, which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression.

  15. Evaluating shielding effectiveness for reducing space radiation cancer risks

    International Nuclear Information System (INIS)

    Cucinotta, Francis A.; Kim, Myung-Hee Y.; Ren, Lei

    2006-01-01

    We discuss calculations of probability distribution functions (PDF) representing uncertainties in projecting fatal cancer risk from galactic cosmic rays (GCR) and solar particle events (SPE). The PDFs are used in significance tests for evaluating the effectiveness of potential radiation shielding approaches. Uncertainties in risk coefficients determined from epidemiology data, dose and dose-rate reduction factors, quality factors, and physics models of radiation environments are considered in models of cancer risk PDFs. Competing mortality risks and functional correlations in radiation quality factor uncertainties are included in the calculations. We show that the cancer risk uncertainty, defined as the ratio of the upper value of 95% confidence interval (CI) to the point estimate is about 4-fold for lunar and Mars mission risk projections. For short-stay lunar missions ( 180d) or Mars missions, GCR risks may exceed radiation risk limits that are based on acceptable levels of risk. For example, the upper 95% CI exceeding 10% fatal risk for males and females on a Mars mission. For reducing GCR cancer risks, shielding materials are marginally effective because of the penetrating nature of GCR and secondary radiation produced in tissue by relativistic particles. At the present time, polyethylene or carbon composite shielding cannot be shown to significantly reduce risk compared to aluminum shielding based on a significance test that accounts for radiobiology uncertainties in GCR risk projection

  16. Profiling Invasiveness in Head and Neck Cancer: Recent Contributions of Genomic and Transcriptomic Approaches

    International Nuclear Information System (INIS)

    Nisa, Lluís; Aebersold, Daniel Matthias; Giger, Roland; Caversaccio, Marco Domenico; Borner, Urs; Medová, Michaela; Zimmer, Yitzhak

    2015-01-01

    High-throughput molecular profiling approaches have emerged as precious research tools in the field of head and neck translational oncology. Such approaches have identified and/or confirmed the role of several genes or pathways in the acquisition/maintenance of an invasive phenotype and the execution of cellular programs related to cell invasion. Recently published new-generation sequencing studies in head and neck squamous cell carcinoma (HNSCC) have unveiled prominent roles in carcinogenesis and cell invasion of mutations involving NOTCH1 and PI3K-patwhay components. Gene-expression profiling studies combined with systems biology approaches have allowed identifying and gaining further mechanistic understanding into pathways commonly enriched in invasive HNSCC. These pathways include antigen-presenting and leucocyte adhesion molecules, as well as genes involved in cell-extracellular matrix interactions. Here we review the major insights into invasiveness in head and neck cancer provided by high-throughput molecular profiling approaches

  17. Profiling Invasiveness in Head and Neck Cancer: Recent Contributions of Genomic and Transcriptomic Approaches

    Directory of Open Access Journals (Sweden)

    Lluís Nisa

    2015-03-01

    Full Text Available High-throughput molecular profiling approaches have emerged as precious research tools in the field of head and neck translational oncology. Such approaches have identified and/or confirmed the role of several genes or pathways in the acquisition/maintenance of an invasive phenotype and the execution of cellular programs related to cell invasion. Recently published new-generation sequencing studies in head and neck squamous cell carcinoma (HNSCC have unveiled prominent roles in carcinogenesis and cell invasion of mutations involving NOTCH1 and PI3K-patwhay components. Gene-expression profiling studies combined with systems biology approaches have allowed identifying and gaining further mechanistic understanding into pathways commonly enriched in invasive HNSCC. These pathways include antigen-presenting and leucocyte adhesion molecules, as well as genes involved in cell-extracellular matrix interactions. Here we review the major insights into invasiveness in head and neck cancer provided by high-throughput molecular profiling approaches.

  18. A pan-cancer analysis of transcriptome changes associated with somatic mutations in U2AF1 reveals commonly altered splicing events.

    Directory of Open Access Journals (Sweden)

    Angela N Brooks

    Full Text Available Although recurrent somatic mutations in the splicing factor U2AF1 (also known as U2AF35 have been identified in multiple cancer types, the effects of these mutations on the cancer transcriptome have yet to be fully elucidated. Here, we identified splicing alterations associated with U2AF1 mutations across distinct cancers using DNA and RNA sequencing data from The Cancer Genome Atlas (TCGA. Using RNA-Seq data from 182 lung adenocarcinomas and 167 acute myeloid leukemias (AML, in which U2AF1 is somatically mutated in 3-4% of cases, we identified 131 and 369 splicing alterations, respectively, that were significantly associated with U2AF1 mutation. Of these, 30 splicing alterations were statistically significant in both lung adenocarcinoma and AML, including three genes in the Cancer Gene Census, CTNNB1, CHCHD7, and PICALM. Cell line experiments expressing U2AF1 S34F in HeLa cells and in 293T cells provide further support that these altered splicing events are caused by U2AF1 mutation. Consistent with the function of U2AF1 in 3' splice site recognition, we found that S34F/Y mutations cause preferences for CAG over UAG 3' splice site sequences. This report demonstrates consistent effects of U2AF1 mutation on splicing in distinct cancer cell types.

  19. Interrogation of transcriptomic changes associated with drug-induced hepatic sinusoidal dilatation in colorectal cancer.

    Science.gov (United States)

    Jarzabek, Monika A; Proctor, William R; Vogt, Jennifer; Desai, Rupal; Dicker, Patrick; Cain, Gary; Raja, Rajiv; Brodbeck, Jens; Stevens, Dale; van der Stok, Eric P; Martens, John W M; Verhoef, Cornelis; Hegde, Priti S; Byrne, Annette T; Tarrant, Jacqueline M

    2018-01-01

    Drug-related sinusoidal dilatation (SD) is a common form of hepatotoxicity associated with oxaliplatin-based chemotherapy used prior to resection of colorectal liver metastases (CRLM). Recently, hepatic SD has also been associated with anti-delta like 4 (DLL4) cancer therapies targeting the NOTCH pathway. To investigate the hypothesis that NOTCH signaling plays an important role in drug-induced SD, gene expression changes were examined in livers from anti-DLL4 and oxaliplatin-induced SD in non-human primate (NHP) and patients, respectively. Putative mechanistic biomarkers of bevacizumab (bev)-mediated protection against oxaliplatin-induced SD were also investigated. RNA was extracted from whole liver sections or centrilobular regions by laser-capture microdissection (LCM) obtained from NHP administered anti-DLL4 fragment antigen-binding (F(ab')2 or patients with CRLM receiving oxaliplatin-based chemotherapy with or without bev. mRNA expression was quantified using high-throughput real-time quantitative PCR. Significance analysis was used to identify genes with differential expression patterns (false discovery rate (FDR) < 0.05). Eleven (CCL2, CCND1, EFNB2, ERG, ICAM1, IL16, LFNG, NOTCH1, NOTCH4, PRDX1, and TGFB1) and six (CDH5, EFNB2, HES1, IL16, MIK67, HES1 and VWF) candidate genes were differentially expressed in the liver of anti-DLL4- and oxaliplatin-induced SD, respectively. Addition of bev to oxaliplatin-based chemotherapy resulted in differential changes in hepatic CDH5, HEY1, IL16, JAG1, MMP9, NOTCH4 and TIMP1 expression. This work implicates NOTCH and IL16 pathways in the pathogenesis of drug-induced SD and further explains the hepato-protective effect of bev in oxaliplatin-induced SD observed in CRLM patients.

  20. A Normalization-Free and Nonparametric Method Sharpens Large-Scale Transcriptome Analysis and Reveals Common Gene Alteration Patterns in Cancers.

    Science.gov (United States)

    Li, Qi-Gang; He, Yong-Han; Wu, Huan; Yang, Cui-Ping; Pu, Shao-Yan; Fan, Song-Qing; Jiang, Li-Ping; Shen, Qiu-Shuo; Wang, Xiao-Xiong; Chen, Xiao-Qiong; Yu, Qin; Li, Ying; Sun, Chang; Wang, Xiangting; Zhou, Jumin; Li, Hai-Peng; Chen, Yong-Bin; Kong, Qing-Peng

    2017-01-01

    Heterogeneity in transcriptional data hampers the identification of differentially expressed genes (DEGs) and understanding of cancer, essentially because current methods rely on cross-sample normalization and/or distribution assumption-both sensitive to heterogeneous values. Here, we developed a new method, Cross-Value Association Analysis (CVAA), which overcomes the limitation and is more robust to heterogeneous data than the other methods. Applying CVAA to a more complex pan-cancer dataset containing 5,540 transcriptomes discovered numerous new DEGs and many previously rarely explored pathways/processes; some of them were validated, both in vitro and in vivo , to be crucial in tumorigenesis, e.g., alcohol metabolism ( ADH1B ), chromosome remodeling ( NCAPH ) and complement system ( Adipsin ). Together, we present a sharper tool to navigate large-scale expression data and gain new mechanistic insights into tumorigenesis.

  1. Reduced vaginal elasticity, reduced lubrication, and deep and superficial dyspareunia in irradiated gynecological cancer survivors.

    Science.gov (United States)

    Stinesen Kollberg, Karin; Waldenström, Ann-Charlotte; Bergmark, Karin; Dunberger, Gail; Rossander, Anna; Wilderäng, Ulrica; Åvall-Lundqvist, Elisabeth; Steineck, Gunnar

    2015-05-01

    The purpose of this study was to examine whether or not vaginal elasticity or lack of lubrication is associated with deep or superficial dyspareunia. We investigated gynecological cancer survivors treated with radiation therapy. In a population-based study with 616 women answering a questionnaire (participation rate 78%) and who were treated with radiotherapy for gynecological cancer, we analyzed information from 243 women (39%) who reported that they had had intercourse during the previous six months. Analyses included log-binomial regression (relative risks) and multiple imputations by chained equations in combination with Bayesian Model Averaging, yielding a posterior probability value. Age range of this cancer recurrent-free group of women was 29-80. Dyspareunia affected 164 of 243 of the women (67%). One hundred thirty-four women (55%) reported superficial pain, 97 women (40%) reported deep pain, and 87 women (36%) reported both types of dyspareunia. The relative risk (RR) of deep dyspareunia was 1.87 (CI 1.41-2.49) with impaired vaginal elasticity compared to normal vaginal elasticity. Age and lower abdominal swelling were separate risk factors for deep dyspareunia. However, effects remain after adjusting for these factors. The relative risk of deep dyspareunia was almost twice as high with impaired vaginal elasticity compared to normal vaginal elasticity. If we wish to treat or even prevent deep dyspareunia in women with gynecological cancer, we may use our knowledge of the pathophysiology of deep dyspareunia and increasingly provide dilators together with instructions on how to use them for stretching exercises in order to retain vaginal elasticity. Results highlight the need for studies with more precise questions distinguishing superficial from deep dyspareunia so that in the future we may be able to primarily try to avoid reduced vaginal elasticity and secondarily reduce the symptoms.

  2. Coupling Deep Transcriptome Analysis with Untargeted Metabolic Profiling in Ophiorrhiza pumila to Further the Understanding of the Biosynthesis of the Anti-Cancer Alkaloid Camptothecin and Anthraquinones

    Science.gov (United States)

    Yamazaki, Mami; Mochida, Keiichi; Asano, Takashi; Nakabayashi, Ryo; Chiba, Motoaki; Udomson, Nirin; Yamazaki, Yasuyo; Goodenowe, Dayan B.; Sankawa, Ushio; Yoshida, Takuhiro; Toyoda, Atsushi; Totoki, Yasushi; Sakaki, Yoshiyuki; Góngora-Castillo, Elsa; Buell, C. Robin; Sakurai, Tetsuya; Saito, Kazuki

    2013-01-01

    The Rubiaceae species, Ophiorrhiza pumila, accumulates camptothecin, an anti-cancer alkaloid with a potent DNA topoisomerase I inhibitory activity, as well as anthraquinones that are derived from the combination of the isochorismate and hemiterpenoid pathways. The biosynthesis of these secondary products is active in O. pumila hairy roots yet very low in cell suspension culture. Deep transcriptome analysis was conducted in O. pumila hairy roots and cell suspension cultures using the Illumina platform, yielding a total of 2 Gb of sequence for each sample. We generated a hybrid transcriptome assembly of O. pumila using the Illumina-derived short read sequences and conventional Sanger-derived expressed sequence tag clones derived from a full-length cDNA library constructed using RNA from hairy roots. Among 35,608 non-redundant unigenes, 3,649 were preferentially expressed in hairy roots compared with cell suspension culture. Candidate genes involved in the biosynthetic pathway for the monoterpenoid indole alkaloid camptothecin were identified; specifically, genes involved in post-strictosamide biosynthetic events and genes involved in the biosynthesis of anthraquinones and chlorogenic acid. Untargeted metabolomic analysis by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) indicated that most of the proposed intermediates in the camptothecin biosynthetic pathway accumulated in hairy roots in a preferential manner compared with cell suspension culture. In addition, a number of anthraquinones and chlorogenic acid preferentially accumulated in hairy roots compared with cell suspension culture. These results suggest that deep transcriptome and metabolome data sets can facilitate the identification of genes and intermediates involved in the biosynthesis of secondary products including camptothecin in O. pumila. PMID:23503598

  3. Replication and virus-induced transcriptome of HAdV-5 in normal host cells versus cancer cells--differences of relevance for adenoviral oncolysis.

    Directory of Open Access Journals (Sweden)

    Dominik E Dorer

    Full Text Available Adenoviruses (Ads, especially HAdV-5, have been genetically equipped with tumor-restricted replication potential to enable applications in oncolytic cancer therapy. Such oncolytic adenoviruses have been well tolerated in cancer patients, but their anti-tumor efficacy needs to be enhanced. In this regard, it should be considered that cancer cells, dependent on their tissue of origin, can differ substantially from the normal host cells to which Ads are adapted by complex virus-host interactions. Consequently, viral replication efficiency, a key determinant of oncolytic activity, might be suboptimal in cancer cells. Therefore, we have analyzed both the replication kinetics of HAdV-5 and the virus-induced transcriptome in human bronchial epithelial cells (HBEC in comparison to cancer cells. This is the first report on genome-wide expression profiling of Ads in their native host cells. We found that E1A expression and onset of viral genome replication are most rapid in HBEC and considerably delayed in melanoma cells. In squamous cell lung carcinoma cells, we observed intermediate HAdV-5 replication kinetics. Infectious particle production, viral spread and lytic activity of HAdV-5 were attenuated in melanoma cells versus HBEC. Expression profiling at the onset of viral genome replication revealed that HAdV-5 induced the strongest changes in the cellular transcriptome in HBEC, followed by lung cancer and melanoma cells. We identified prominent regulation of genes involved in cell cycle and DNA metabolism, replication and packaging in HBEC, which is in accord with the necessity to induce S phase for viral replication. Strikingly, in melanoma cells HAdV-5 triggered opposing regulation of said genes and, in contrast to lung cancer cells, no weak S phase induction was detected when using the E2F promoter as reporter. Our results provide a rationale for improving oncolytic adenoviruses either by adaptation of viral infection to target tumor cells or by

  4. Genome, transcriptome and methylome sequencing of a primitively eusocial wasp reveal a greatly reduced DNA methylation system in a social insect.

    Science.gov (United States)

    Standage, Daniel S; Berens, Ali J; Glastad, Karl M; Severin, Andrew J; Brendel, Volker P; Toth, Amy L

    2016-04-01

    Comparative genomics of social insects has been intensely pursued in recent years with the goal of providing insights into the evolution of social behaviour and its underlying genomic and epigenomic basis. However, the comparative approach has been hampered by a paucity of data on some of the most informative social forms (e.g. incipiently and primitively social) and taxa (especially members of the wasp family Vespidae) for studying social evolution. Here, we provide a draft genome of the primitively eusocial model insect Polistes dominula, accompanied by analysis of caste-related transcriptome and methylome sequence data for adult queens and workers. Polistes dominula possesses a fairly typical hymenopteran genome, but shows very low genomewide GC content and some evidence of reduced genome size. We found numerous caste-related differences in gene expression, with evidence that both conserved and novel genes are related to caste differences. Most strikingly, these -omics data reveal a major reduction in one of the major epigenetic mechanisms that has been previously suggested to be important for caste differences in social insects: DNA methylation. Along with a conspicuous loss of a key gene associated with environmentally responsive DNA methylation (the de novo DNA methyltransferase Dnmt3), these wasps have greatly reduced genomewide methylation to almost zero. In addition to providing a valuable resource for comparative analysis of social insect evolution, our integrative -omics data for this important behavioural and evolutionary model system call into question the general importance of DNA methylation in caste differences and evolution in social insects. © 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  5. How can attrition rates be reduced in cancer drug discovery?

    Science.gov (United States)

    Moreno, Lucas; Pearson, Andrew D J

    2013-04-01

    Attrition is a major issue in anticancer drug development with up to 95% of drugs tested in Phase I trials not reaching a marketing authorisation making the drug development process enormously costly and inefficient. It is essential that this problem is addressed throughout the whole drug development process to improve efficiency which will ultimately result in increased patient benefit with more profitable drugs. The approach to reduce cancer drug attrition rates must be based on three pillars. The first of these is that there is a need for new pre-clinical models which can act as better predictors of success in clinical trials. Furthermore, clinical trials driven by tumour biology with the incorporation of predictive and pharmacodynamic biomarkers would be beneficial in drug development. Finally, there is a need for increased collaboration to combine the unique strengths between industry, academia and regulators to ensure that the needs of all stakeholders are met.

  6. IMRT for head and neck cancer: reducing xerostomia and dysphagia

    International Nuclear Information System (INIS)

    Wang, XiaoShen; Eisbruch, Avraham

    2016-01-01

    Dysphagia and xerostomia are the main sequellae of chemoradiotherapy for head and neck cancer, and the main factors in reducing long-term patient quality of life. IMRT uses advanced technology to focus the high radiation doses on the targets and avoid irradiation of non-involved tissues. The decisions about sparing organs and tissues whose damage causes xerostomia and dysphagia depends on the evidence for dose–response relationships for the organs causing these sequellae. This paper discusses the evidence for the contribution of radiotherapy to xerostomia via damage of the major salivary glands (parotid and submandibular) and minor salivary glands within the oral cavity, and the contribution of radiotherapy-related effect on important swallowing structures causing dysphagia. Recommendations for dose limits to these organs, based on measurements of xerostomia and dysphagia following radiotherapy, are provided here

  7. [Effectiveness of prayer in reducing anxiety in cancer patients].

    Science.gov (United States)

    Carvalho, Camila Csizmar; Chaves, Erika de Cássia Lopes; Iunes, Denise Hollanda; Simão, Talita Prado; Grasselli, Cristiane da Silva Marciano; Braga, Cristiane Giffoni

    2014-08-01

    To evaluate the effect of prayer on anxiety in cancer patients undergoing chemotherapy. Quasi-experimental study, with pre and post-intervention. Twenty patients admitted to treatment of continuous intravenous chemotherapy were recruited. The volunteers were evaluated through interviews using a questionnaire of sociodemographic, clinical and spiritual characteristics, the Index of Religiosity Duke University and the State-Trait Anxiety Inventory. Vital signs were measured and collected salivary cortisol. The intervention was applied prayer and data collection occurred in three phases: first collection (baseline), pre and post-intervention. The data found between the pre and post-intervention samples showed different statistically significant for state anxiety (p= Prayer, therefore, proved to be an effective strategy in reducing the anxiety of the patient undergoing chemotherapy.

  8. Oral cryotherapy reduced oral mucositis in patients having cancer treatments.

    Science.gov (United States)

    Spivakovsky, Sylvia

    2016-09-01

    Data sourcesCochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CANCERLIT, CINAHL, the US National Institutes of Health Trials Registry and the WHO Clinical Trials Registry Platform.Study selectionRandomised controlled trials (RCTs) assessing the effects of oral cryotherapy in patients with cancer receiving treatment compared to usual care, no treatment or other interventions to prevent mucositis. The primary outcome was incidence of mucositis and its severity.Data extraction and synthesisTwo reviewers carried out study assessment and data extraction independently. Treatment effect for continuous data was calculated using mean values and standard deviations and expressed as mean difference (MD) and 95% confidence interval. Risk ratio (RR) was calculated for dichotomous data. Meta-analysis was performed.ResultsFourteen studies with 1280 participants were included. Subgroup analysis was undertaken according to the main cancer treatment type. Cryotherapy reduced the risk of developing mucositis by 39% (RR = 0.61; 95%CI, 0.52 to 0.72) on patients treated with fluorouracil (5FU). For melphalan-based treatment the risk of developing mucositis was reduced by 41% (RR =0.59; 95%CI, 0.35 to 1.01). Oral cryotherapy was shown to be safe, with very low rates of minor adverse effects, such as headaches, chills, numbness/taste disturbance and tooth pain. This appears to contribute to the high rates of compliance seen in the included studies.ConclusionsThere is confidence that oral cryotherapy leads to a large reduction in oral mucositis in adults treated with 5FU. Although there is less certainty on the size of the reduction on patients treated with melphalan, it is certain there is reduction of severe mucositis.

  9. Transcriptomic changes underlie altered egg protein production and reduced fecundity in an estuarine model fish exposed to bifenthrin.

    Science.gov (United States)

    Brander, Susanne M; Jeffries, Ken M; Cole, Bryan J; DeCourten, Bethany M; White, J Wilson; Hasenbein, Simone; Fangue, Nann A; Connon, Richard E

    2016-05-01

    PCR demonstrated that bifenthrin downregulates a number of estrogen-related transcripts, particularly at the lowest exposure level. Choriogenin protein also decreased with exposure to increasing concentrations of bifenthrin, and adult M. beryllina exposed to 0.5ng/L had significantly reduced reproductive output (fertilized eggs per female). This reduction in fecundity is consistent with observed changes in endocrine-related gene expression and choriogenin production. Taken together, our results demonstrate that environmental concentrations of bifenthrin have potential to interfere with metabolic processes, endocrine signaling, and to decrease reproductive output. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Transcriptome sequencing revealed differences in the response of renal cancer cells to hypoxia and CoCl2 treatment [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Nadezhda Zhigalova

    2015-12-01

    Full Text Available Human cancer cells are subjected to hypoxic conditions in many tumours. Hypoxia causes alterations in the glycolytic pathway activation through stabilization of hypoxia-inducible factor 1. Currently, two approaches are commonly used to model hypoxia: an alternative to generating low-oxygen conditions in an incubator, cells can be treated with CoCl2. We performed RNA-seq experiments to study transcriptomes of human Caki-1 cells under real hypoxia and after CoCl2 treatment. Despite causing transcriptional changes of a much higher order of magnitude for the genes in the hypoxia regulation pathway, CoCl2 treatment fails to induce alterations in the glycolysis / gluconeogenesis pathway. Moreover, CoCl2 caused aberrant activation of other oxidoreductases in glycine, serine and threonine metabolism pathways.

  11. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer:

    DEFF Research Database (Denmark)

    Vale, Claire; Jakobsen, Anders

    2008-01-01

    BACKGROUND: After a 1999 National Cancer Institute (NCI) clinical alert was issued, chemoradiotherapy has become widely used in treating women with cervical cancer. Two subsequent systematic reviews found that interpretation of the benefits was complicated, and some important clinical questions...

  12. MiRNA Transcriptome Profiling of Spheroid-Enriched Cells with Cancer Stem Cell Properties in Human Breast MCF-7 Cell Line

    Science.gov (United States)

    Boo, Lily; Ho, Wan Yong; Ali, Norlaily Mohd; Yeap, Swee Keong; Ky, Huynh; Chan, Kok Gan; Yin, Wai Fong; Satharasinghe, Dilan Amila; Liew, Woan Charn; Tan, Sheau Wei; Ong, Han Kiat; Cheong, Soon Keng

    2016-01-01

    Breast cancer is the second leading cause of cancer-related mortality worldwide as most patients often suffer cancer relapse. The reason is often attributed to the presence of cancer stem cells (CSCs). Recent studies revealed that dysregulation of microRNA (miRNA) are closely linked to breast cancer recurrence and metastasis. However, no specific study has comprehensively characterised the CSC characteristic and miRNA transcriptome in spheroid-enriched breast cells. This study described the generation of spheroid MCF-7 cell in serum-free condition and the comprehensive characterisation for their CSC properties. Subsequently, miRNA expression differences between the spheroid-enriched CSC cells and their parental cells were evaluated using next generation sequencing (NGS). Our results showed that the MCF-7 spheroid cells were enriched with CSCs properties, indicated by the ability to self-renew, increased expression of CSCs markers, and increased resistance to chemotherapeutic drugs. Additionally, spheroid-enriched CSCs possessed greater cell proliferation, migration, invasion, and wound healing ability. A total of 134 significantly (p<0.05) differentially expressed miRNAs were identified between spheroids and parental cells using miRNA-NGS. MiRNA-NGS analysis revealed 25 up-regulated and 109 down-regulated miRNAs which includes some miRNAs previously reported in the regulation of breast CSCs. A number of miRNAs (miR-4492, miR-4532, miR-381, miR-4508, miR-4448, miR-1296, and miR-365a) which have not been previously reported in breast cancer were found to show potential association with breast cancer chemoresistance and self-renewal capability. The gene ontology (GO) analysis showed that the predicted genes were enriched in the regulation of metabolic processes, gene expression, DNA binding, and hormone receptor binding. The corresponding pathway analyses inferred from the GO results were closely related to the function of signalling pathway, self

  13. Cancer statistics for African Americans, 2016: Progress and opportunities in reducing racial disparities.

    Science.gov (United States)

    DeSantis, Carol E; Siegel, Rebecca L; Sauer, Ann Goding; Miller, Kimberly D; Fedewa, Stacey A; Alcaraz, Kassandra I; Jemal, Ahmedin

    2016-07-01

    In this article, the American Cancer Society provides the estimated number of new cancer cases and deaths for blacks in the United States and the most recent data on cancer incidence, mortality, survival, screening, and risk factors for cancer. Incidence data are from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries, and mortality data are from the National Center for Health Statistics. Approximately 189,910 new cases of cancer and 69,410 cancer deaths will occur among blacks in 2016. Although blacks continue to have higher cancer death rates than whites, the disparity has narrowed for all cancers combined in men and women and for lung and prostate cancers in men. In contrast, the racial gap in death rates has widened for breast cancer in women and remained level for colorectal cancer in men. The reduction in overall cancer death rates since the early 1990s translates to the avoidance of more than 300,000 deaths among blacks. In men, incidence rates from 2003 to 2012 decreased for all cancers combined (by 2.0% per year) as well as for the top 3 cancer sites (prostate, lung, and colorectal). In women, overall rates during the corresponding time period remained unchanged, reflecting increasing trends in breast cancer combined with decreasing trends in lung and colorectal cancer rates. Five-year relative survival is lower for blacks than whites for most cancers at each stage of diagnosis. The extent to which these disparities reflect unequal access to health care versus other factors remains an active area of research. Progress in reducing cancer death rates could be accelerated by ensuring equitable access to prevention, early detection, and high-quality treatment. CA Cancer J Clin 2016;66:290-308. © 2016 American Cancer Society. © 2016 American Cancer Society, Inc.

  14. Metabolomics and transcriptomics identify pathway differences between visceral and subcutaneous adipose tissue in colorectal cancer patients: the ColoCare study.

    Science.gov (United States)

    Liesenfeld, David B; Grapov, Dmitry; Fahrmann, Johannes F; Salou, Mariam; Scherer, Dominique; Toth, Reka; Habermann, Nina; Böhm, Jürgen; Schrotz-King, Petra; Gigic, Biljana; Schneider, Martin; Ulrich, Alexis; Herpel, Esther; Schirmacher, Peter; Fiehn, Oliver; Lampe, Johanna W; Ulrich, Cornelia M

    2015-08-01

    Metabolic and transcriptomic differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) compartments, particularly in the context of obesity, may play a role in colorectal carcinogenesis. We investigated the differential functions of their metabolic compositions. Biochemical differences between adipose tissues (VAT compared with SAT) in patients with colorectal carcinoma (CRC) were investigated by using mass spectrometry metabolomics and gene expression profiling. Metabolite compositions were compared between VAT, SAT, and serum metabolites. The relation between patients' tumor stage and metabolic profiles was assessed. Presurgery blood and paired VAT and SAT samples during tumor surgery were obtained from 59 CRC patients (tumor stages I-IV) of the ColoCare cohort. Gas chromatography time-of-flight mass spectrometry and liquid chromatography quadrupole time-of-flight mass spectrometry were used to measure 1065 metabolites in adipose tissue (333 identified compounds) and 1810 metabolites in serum (467 identified compounds). Adipose tissue gene expression was measured by using Illumina's HumanHT-12 Expression BeadChips. Compared with SAT, VAT displayed elevated markers of inflammatory lipid metabolism, free arachidonic acid, phospholipases (PLA2G10), and prostaglandin synthesis-related enzymes (PTGD/PTGS2S). Plasmalogen concentrations were lower in VAT than in SAT, which was supported by lower gene expression of FAR1, the rate-limiting enzyme for ether-lipid synthesis in VAT. Serum sphingomyelin concentrations were inversely correlated (P = 0.0001) with SAT adipose triglycerides. Logistic regression identified lipids in patients' adipose tissues, which were associated with CRC tumor stage. As one of the first studies, we comprehensively assessed differences in metabolic, lipidomic, and transcriptomic profiles between paired human VAT and SAT and their association with CRC tumor stage. We identified markers of inflammation in VAT, which

  15. Adherence of Primary Care Physicians to Evidence-Based Recommendations to Reduce Ovarian Cancer Mortality

    OpenAIRE

    Stewart, Sherri L.; Townsend, Julie S.; Puckett, Mary C.; Rim, Sun Hee

    2016-01-01

    Ovarian cancer is the deadliest gynecologic cancer. Receipt of treatment from a gynecologic oncologist is an evidence-based recommendation to reduce mortality from the disease. We examined knowledge and application of this evidence-based recommendation in primary care physicians as part of CDC gynecologic cancer awareness campaign efforts and discussed results in the context of CDC National Comprehensive Cancer Control Program (NCCCP). We analyzed primary care physician responses to questions...

  16. Dietary Fish Oil in Reducing Bone Metastasis of Breast Cancer

    National Research Council Canada - National Science Library

    Ghosh-Choudhury, Nandini

    2006-01-01

    In a study of the mechanism behind the inhibitory effect of fish oil on the growth of breast cancer cells, the authors reported that fish oil, or w-3 polyunsaturated fatty acids (PUFAs), did the following: (1...

  17. Survivorship Care in Reducing Symptoms in Young Adult Cancer Survivors

    Science.gov (United States)

    2017-10-13

    Breast Carcinoma; Cancer Survivor; Depression; Fatigue; Leukemia; Lymphoma; Malignant Bone Neoplasm; Malignant Digestive System Neoplasm; Malignant Female Reproductive System Neoplasm; Malignant Male Reproductive System Neoplasm; Pain; Sleep Disorder; Soft Tissue Sarcoma

  18. Developing Partnerships to Reduce Disparities in Cancer Screening

    OpenAIRE

    Breslau, Erica S.; Rochester, Phyllis W.; Saslow, Debbie; Crocoll, Caroline E.; Johnson, Lenora E.; Vinson, Cynthia A.

    2010-01-01

    Background Interventions in scientific settings to improve the well-being of women who are not regularly screened for cancer have failed. Consequently, community-based prevention and control efforts are needed. Community Context From 2003 through 2007, three federal agencies and 1 nongovernmental agency collaborated with county-level public health counterparts from 6 states to address screening disparities in cervical and breast cancer in counties with the highest prevalence. This case study ...

  19. Folic acid induces cell type-specific changes in the transcriptome of breast cancer cell lines: a proof-of-concept study.

    Science.gov (United States)

    Price, R Jordan; Lillycrop, Karen A; Burdge, Graham C

    2016-01-01

    The effect of folic acid (FA) on breast cancer (BC) risk is uncertain. We hypothesised that this uncertainty may be due, in part, to differential effects of FA between BC cells with different phenotypes. To test this we investigated the effect of treatment with FA concentrations within the range of unmetabolised FA reported in humans on the expression of the transcriptome of non-transformed (MCF10A) and cancerous (MCF7 and Hs578T) BC cells. The total number of transcripts altered was: MCF10A, seventy-five (seventy up-regulated); MCF7, twenty-four (fourteen up-regulated); and Hs578T, 328 (156 up-regulated). Only the cancer-associated gene TAGLN was altered by FA in all three cell lines. In MCF10A and Hs578T cells, FA treatment decreased pathways associated with apoptosis, cell death and senescence, but increased those associated with cell proliferation. The folate transporters SLC19A1, SLC46A1 and FOLR1 were differentially expressed between cell lines tested. However, the level of expression was not altered by FA treatment. These findings suggest that physiological concentrations of FA can induce cell type-specific changes in gene regulation in a manner that is consistent with proliferative phenotype. This has implications for understanding the role of FA in BC risk. In addition, these findings support the suggestion that differences in gene expression induced by FA may involve differential activities of folate transporters. Together these findings indicate the need for further studies of the effect of FA on BC.

  20. Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence.

    Science.gov (United States)

    Bernstein, Harris; Prasad, Anil; Holubec, Hana; Bernstein, Carol; Payne, Claire M; Ramsey, Lois; Dvorakova, Katerina; Wilson, Megan; Warneke, James A; Garewal, Harinder

    2006-06-01

    Pms2 protein is a component of the DNA mismatch repair complex responsible both for post-replication correction of DNA nucleotide mispairs and for early steps in apoptosis. Germline mutations in DNA mismatch repair genes give rise to hereditary non-polyposis colon cancer, which accounts for about 4% of colon cancers. However, little is known about the expression of mismatch repair proteins in relation to sporadic colon cancer, which accounts for the great majority of colon cancers. Multiple samples were taken from the non-neoplastic flat mucosa of colon resections from patients with no colonic neoplasia, a tubulovillous adenoma, or an adenocarcinoma. Expression of Pms2 was assessed using semiquantitative immunohistochemistry. Apoptosis was assessed in polychrome-stained epoxy sections using morphologic criteria. Samples from patients without colonic neoplasia had moderate to strong staining for Pms2 in cell nuclei at the base of crypts, while samples from 2 of the 3 colons with a tubulovillous adenoma, and from 6 of the 10 colons with adenocarcinomas, showed reduced Pms2 expression. Samples from patients with an adenocarcinoma that had reduced Pms2 expression also exhibited reduced apoptosis capability in nearby tissue samples, evidenced when this paired tissue was stressed ex vivo with bile acid. Reduced Pms2 expression in the colonic mucosa may be an early step in progression to colon cancer. This reduction may cause decreased mismatch repair, increased genetic instability, and/or reduced apoptotic capability. Immunohistochemical determination of reduced Pms2 expression, upon further testing, may prove to be a promising early biomarker of risk of progression to malignancy.

  1. Reduced Lung Cancer Mortality With Lower Atmospheric Pressure.

    Science.gov (United States)

    Merrill, Ray M; Frutos, Aaron

    2018-01-01

    Research has shown that higher altitude is associated with lower risk of lung cancer and improved survival among patients. The current study assessed the influence of county-level atmospheric pressure (a measure reflecting both altitude and temperature) on age-adjusted lung cancer mortality rates in the contiguous United States, with 2 forms of spatial regression. Ordinary least squares regression and geographically weighted regression models were used to evaluate the impact of climate and other selected variables on lung cancer mortality, based on 2974 counties. Atmospheric pressure was significantly positively associated with lung cancer mortality, after controlling for sunlight, precipitation, PM2.5 (µg/m 3 ), current smoker, and other selected variables. Positive county-level β coefficient estimates ( P atmospheric pressure were observed throughout the United States, higher in the eastern half of the country. The spatial regression models showed that atmospheric pressure is positively associated with age-adjusted lung cancer mortality rates, after controlling for other selected variables.

  2. Dietary turmeric potentially reduces the risk of cancer.

    Science.gov (United States)

    Hutchins-Wolfbrandt, Amanda; Mistry, Anahita M

    2011-01-01

    Turmeric, a plant rhizome that is often dried, ground and used as a cooking spice, has also been used medicinally for several thousand years. Curcumin, the phytochemical that gives turmeric its golden color, is responsible for most of the therapeutic effects of turmeric. In recent years curcumin has been studied for its effects on chronic diseases such as diabetes, Alzheimer's, and cancer. Though many researchers are investigating turmeric/curcumin in cancer therapy, there is little epidemiologic information on the effects of turmeric consumption. With limited availability of pharmacologic interventions in many areas of the world, use of turmeric in the diet may help to alleviate some of the disease burden through prevention. Here we provide a brief overview of turmeric consumption in different parts of the world, cancer rates in those regions, possible biochemical mechanisms by which turmeric acts and practical recommendations based on the information available.

  3. Comparative transcriptome analysis links distinct peritoneal tumor spread types, miliary and non-miliary, with putative origin, tubes and ovaries, in high grade serous ovarian cancer.

    Science.gov (United States)

    Auer, Katharina; Bachmayr-Heyda, Anna; Aust, Stefanie; Grunt, Thomas W; Pils, Dietmar

    2017-03-01

    High grade serous ovarian cancer (HGSOC) is characterized by extensive local, i.e. peritoneal, tumor spread, manifested in two different clinical presentations, miliary (many millet sized peritoneal implants) and non-miliary (few large exophytically growing peritoneal nodes), and an overall unfavorable outcome. HGSOC is thought to arise from fallopian tube secretory epithelial cells, via so called serous tubal intraepithelial carcinomas (STICs) but an ovarian origin was never ruled out for at least some cases. Comparative transcriptome analyses of isolated tumor cells from fresh HGSOC tissues and (immortalized) ovarian surface epithelial and fallopian tube secretory epithelial cell lines revealed a close relation between putative origin and tumor spread characteristic, i.e. miliary from tubes and non-miliary from ovaries. The latter were characterized by more mesenchymal cell characteristics, more adaptive tumor immune infiltration, and a favorable overall survival. Several molecular sub-classification systems (Crijns' overall survival signature, Yoshihara's subclasses, and a collagen-remodeling signature) seem to already indicate origin. Putative origin alone is a significant independent predictor for HGSOC outcome, validated in independent patient cohorts. Characteristics of both spread types could guide development of new targeted therapeutics, which are urgently needed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. A cohort study of permanently reduced work ability in breast cancer patients.

    Science.gov (United States)

    Hauglann, Beate; Benth, Jūratė Šaltytė; Fosså, Sophie D; Dahl, Alv A

    2012-09-01

    The aims of this cohort study were to explore various longitudinal aspects of employment and disability pension due to permanently reduced work ability among women with breast cancer and to investigate the impact of breast cancer on income. In a national register-based controlled cohort study from Norway, 1,548 women diagnosed with breast cancer (all stages) between 1992 and 1996 at the age 45-54 years and 1,548 cancer-free women matched for age, municipality and civil status were followed for up to 14 years. Medical data from the Cancer Registry of Norway were linked with longitudinal data on employment, social security benefits and socio-demography collected from other national official registries. Compared to cancer-free controls, breast cancer patients were significantly more likely to receive disability pension (hazard ratio (HR) 2.7, 95% CI 2.3-3.2) after adjustment for unmatched socio-demographic variables (education, income and children employment rates were higher in non-disabled patients than in non-disabled controls (82% vs. 77%, p = 0.008). Working breast cancer patients experienced a temporary negative effect on employment income. A considerable proportion of women with breast cancer will over time experience permanently reduced work ability and become disability pension holders. In case of reduced work ability in breast cancer survivors, medical personel caring for them should consider and discuss with them rehabilitation and workplace adjustment in order to prevent early disability pension.

  5. Reducing behavioural risk factors for cancer: An affect regulation perspective.

    Science.gov (United States)

    O'Leary, Daniel; Suri, Gaurav; Gross, James J

    2018-01-01

    Nearly half of all cancer deaths are attributable to preventable causes, primarily unhealthy behaviours such as tobacco use, alcohol use and overeating. In this review, we argue that people engage in these behaviours, at least in part, as a means of regulating their affective states. To better understand why people engage in these behaviours and how researchers might design interventions to promote the selection of healthier methods for regulating affect, we propose a conceptual model of affect regulation. We synthesise research from both the stress and coping tradition as well as the emotion and emotion regulation tradition, two literatures that are not typically integrated. In so doing, we indicate where researchers have made headway in understanding these behaviours as affect regulation and note how our model could be used to structure future work in a way that would be particularly advantageous to cancer control efforts.

  6. Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; Neuhaus, Jacqueline; Babiker, Abdel G

    2016-01-01

    BACKGROUND:  In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts a...

  7. Grantee Spotlight: Marvella Ford, Ph.D. - Reducing Barriers to Surgical Cancer Care among African Am

    Science.gov (United States)

    Drs. Marvella E. Ford and Nestor F. Esnaola were awarded a five-year NIH/NIMHD R01 grant to evaluate a patient navigation intervention to reduce barriers to surgical cancer care and improving surgical resection rates in African Americans with lung cancer.

  8. Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer.

    Science.gov (United States)

    Brägelmann, Johannes; Klümper, Niklas; Offermann, Anne; von Mässenhausen, Anne; Böhm, Diana; Deng, Mario; Queisser, Angela; Sanders, Christine; Syring, Isabella; Merseburger, Axel S; Vogel, Wenzel; Sievers, Elisabeth; Vlasic, Ignacija; Carlsson, Jessica; Andrén, Ove; Brossart, Peter; Duensing, Stefan; Svensson, Maria A; Shaikhibrahim, Zaki; Kirfel, Jutta; Perner, Sven

    2017-04-01

    Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches. Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities ( n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer ( n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq. Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancer was marked by high expression of CDK19 In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8 were present in metastases. In vitro , inhibition of CDK19 and CDK8 by knockdown or treatment with a selective CDK8/CDK19 inhibitor significantly decreased migration and invasion. Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer. Clin Cancer Res; 23(7); 1829-40. ©2016 AACR . ©2016 American Association for Cancer Research.

  9. Study Shows Aspirin Reduces Colorectal Cancer in Those at High Risk

    Science.gov (United States)

    Findings from the first large clinical trial of its kind indicate that taking high doses of aspirin daily for at least 2 years substantially reduces the risk of colorectal cancer among people at increased risk of the disease.

  10. Breastfeeding Reduces Breast Cancer Risk: A Case-Control Study in North India

    Directory of Open Access Journals (Sweden)

    Babita

    2014-01-01

    Conclusions: Breastfeeding has a significant role in reducing breast cancer, and so information, education, and communication activities for the promotion of breastfeeding and creating awareness about this fatal disease are the need of the hour.

  11. Transcriptome Analysis of Individual Stromal Cell Populations Identifies Stroma-Tumor Crosstalk in Mouse Lung Cancer Model

    Directory of Open Access Journals (Sweden)

    Hyejin Choi

    2015-02-01

    Full Text Available Emerging studies have begun to demonstrate that reprogrammed stromal cells play pivotal roles in tumor growth, metastasis, and resistance to therapy. However, the contribution of stromal cells to non-small-cell lung cancer (NSCLC has remained underexplored. We used an orthotopic model of Kras-driven NSCLC to systematically dissect the contribution of specific hematopoietic stromal cells in lung cancer. RNA deep-sequencing analysis of individually sorted myeloid lineage and tumor epithelial cells revealed cell-type-specific differentially regulated genes, indicative of activated stroma. We developed a computational model for crosstalk signaling discovery based on ligand-receptor interactions and downstream signaling networks and identified known and novel tumor-stroma paracrine and tumor autocrine crosstalk-signaling pathways in NSCLC. We provide cellular and molecular insights into components of the lung cancer microenvironment that contribute to carcinogenesis. This study has the potential for development of therapeutic strategies that target tumor-stroma interactions and may complement conventional anti-cancer treatments.

  12. Transcriptome analyses of rhesus monkey preimplantation embryos reveal a reduced capacity for DNA double-strand break repair in primate oocytes and early embryos

    Science.gov (United States)

    Wang, Xinyi; Liu, Denghui; He, Dajian; Suo, Shengbao; Xia, Xian; He, Xiechao; Han, Jing-Dong J.; Zheng, Ping

    2017-01-01

    Preimplantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA), and cell-fate commitment. The molecular basis of these processes remains obscure in primates in which there is a high rate of embryo wastage. Thus, understanding the factors involved in genome reprogramming and ZGA might help reproductive success during this susceptible period of early development and generate induced pluripotent stem cells with greater efficiency. Moreover, explaining the molecular basis responsible for embryo wastage in primates will greatly expand our knowledge of species evolution. By using RNA-seq in single and pooled oocytes and embryos, we defined the transcriptome throughout preimplantation development in rhesus monkey. In comparison to archival human and mouse data, we found that the transcriptome dynamics of monkey oocytes and embryos were very similar to those of human but very different from those of mouse. We identified several classes of maternal and zygotic genes, whose expression peaks were highly correlated with the time frames of genome reprogramming, ZGA, and cell-fate commitment, respectively. Importantly, comparison of the ZGA-related network modules among the three species revealed less robust surveillance of genomic instability in primate oocytes and embryos than in rodents, particularly in the pathways of DNA damage signaling and homology-directed DNA double-strand break repair. This study highlights the utility of monkey models to better understand the molecular basis for genome reprogramming, ZGA, and genomic stability surveillance in human early embryogenesis and may provide insights for improved homologous recombination-mediated gene editing in monkey. PMID:28223401

  13. A novel model to combine clinical and pathway-based transcriptomic information for the prognosis prediction of breast cancer.

    Directory of Open Access Journals (Sweden)

    Sijia Huang

    2014-09-01

    Full Text Available Breast cancer is the most common malignancy in women worldwide. With the increasing awareness of heterogeneity in breast cancers, better prediction of breast cancer prognosis is much needed for more personalized treatment and disease management. Towards this goal, we have developed a novel computational model for breast cancer prognosis by combining the Pathway Deregulation Score (PDS based pathifier algorithm, Cox regression and L1-LASSO penalization method. We trained the model on a set of 236 patients with gene expression data and clinical information, and validated the performance on three diversified testing data sets of 606 patients. To evaluate the performance of the model, we conducted survival analysis of the dichotomized groups, and compared the areas under the curve based on the binary classification. The resulting prognosis genomic model is composed of fifteen pathways (e.g., P53 pathway that had previously reported cancer relevance, and it successfully differentiated relapse in the training set (log rank p-value = 6.25e-12 and three testing data sets (log rank p-value < 0.0005. Moreover, the pathway-based genomic models consistently performed better than gene-based models on all four data sets. We also find strong evidence that combining genomic information with clinical information improved the p-values of prognosis prediction by at least three orders of magnitude in comparison to using either genomic or clinical information alone. In summary, we propose a novel prognosis model that harnesses the pathway-based dysregulation as well as valuable clinical information. The selected pathways in our prognosis model are promising targets for therapeutic intervention.

  14. Feasibility of Reduced Port Laparoscopic Colectomy for Colon Cancer.

    Science.gov (United States)

    Tsutsumi, Soichi; Morita, Hiroki; Fujii, Takaaki; Suto, Toshinaga; Yajima, Reina; Takada, Takahiro; Asao, Takayuki; Kuwano, Hiroyuki

    2015-06-01

    Reduced port laparoscopic surgery has recently emerged as a method to improve the cosmetic results of conventional laparoscopic surgery. We reported our technique of reduced port laparoscopic colectomy using 3-port and short-time outcomes. Between 2005 and 2012, we performed 161 reduced port laparoscopic colectomies using the 3-port technique. Data analyzed in-cluded age, gender, body mass index (BMI), duration of surgery, number of harvested lymph nodes, and duration of hospital stay. All of the cases were successfully performed using the 3-port procedure. The median durations of surgery and postoperative hospital stay were 140 mm (range 75-463 mm) and 9 days (range 5-38 days), respectively. No mortality was associated with this technique. Reduced port laparoscopic colectomy is feasible and may have advantages over conventional laparoscopic colectomy.

  15. Are we able to reduce the mortality and morbidity of oral cancer; Some considerations

    Science.gov (United States)

    2013-01-01

    Oral cancer makes up 1%-2% of all cancers that may arise in the body. The majority of oral cancers consists of squamous cell carcinomas. Oral cancer carries a considerable mortality rate, being mainly dependent on the stage of the disease at admission. Worldwide some 50% of the patients with oral cancer present with advanced disease. There are several ways of trying to diagnose oral cancer in a lower tumor stage, being 1) mass screening or screening in selected patients, 2) reduction of patients’ delay, and 3) reduction of doctors’ delay. Oral cancer population-based screening (“mass screening”) programs do not meet the guidelines for a successful outcome. There may be some benefit when focusing on high-risk groups, such as heavy smokers and heavy drinkers. Reported reasons for patients’ delay range from fear of a diagnosis of cancer, limited accessibility of primary health care, to unawareness of the possibility of malignant oral diseases. Apparently, information campaigns in news programs and TV have little effect on patients’ delay. Mouth self-examination may have some value in reducing patients’ delay. Doctors’ delay includes dentists’ delay and diagnostic delay caused by other medical and dental health care professionals. Doctors’ delay may vary from almost zero days up to more than six months. Usually, morbidity of cancer treatment is measured by quality of life (QoL) questionnaires. In the past decades this topic has drawn a lot of attention worldwide. It is a challenge to decrease the morbidity that is associated with the various treatment modalities that are used in oral cancer without substantially compromising the survival rate. Smoking cessation contributes to reducing the risk of oral cancers, with a 50% reduction in risk within five years. Indeed, risk factor reduction seems to be the most effective tool in an attempt to decrease the morbidity and mortality of oral cancer. Key words:Oral cancer, early diagnosis, quality of life

  16. Changes in the transcriptome of the human endometrial Ishikawa cancer cell line induced by estrogen, progesterone, tamoxifen, and mifepristone (RU486 as detected by RNA-sequencing.

    Directory of Open Access Journals (Sweden)

    Karin Tamm-Rosenstein

    Full Text Available BACKGROUND: Estrogen (E2 and progesterone (P4 are key players in the maturation of the human endometrium. The corresponding steroid hormone modulators, tamoxifen (TAM and mifepristone (RU486 are widely used in breast cancer therapy and for contraception purposes, respectively. METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiling of the human endometrial Ishikawa cancer cell line treated with E2 and P4 for 3 h and 12 h, and TAM and RU486 for 12 h, was performed using RNA-sequencing. High levels of mRNA were detected for genes, including PSAP, ATP5G2, ATP5H, and GNB2L1 following E2 or P4 treatment. A total of 82 biomarkers for endometrial biology were identified among E2 induced genes, and 93 among P4 responsive genes. Identified biomarkers included: EZH2, MDK, MUC1, SLIT2, and IL6ST, which are genes previously associated with endometrial receptivity. Moreover, 98.8% and 98.6% of E2 and P4 responsive genes in Ishikawa cells, respectively, were also detected in two human mid-secretory endometrial biopsy samples. TAM treatment exhibited both antagonistic and agonistic effects of E2, and also regulated a subset of genes independently. The cell cycle regulator cyclin D1 (CCND1 showed significant up-regulation following treatment with TAM. RU486 did not appear to act as a pure antagonist of P4 and a functional analysis of RU486 response identified genes related to adhesion and apoptosis, including down-regulated genes associated with cell-cell contacts and adhesion as CTNND1, JUP, CDH2, IQGAP1, and COL2A1. CONCLUSIONS: Significant changes in gene expression by the Ishikawa cell line were detected after treatments with E2, P4, TAM, and RU486. These transcriptome data provide valuable insight into potential biomarkers related to endometrial receptivity, and also facilitate an understanding of the molecular changes that take place in the endometrium in the early stages of breast cancer treatment and contraception usage.

  17. ChimerDB 3.0: an enhanced database for fusion genes from cancer transcriptome and literature data mining.

    Science.gov (United States)

    Lee, Myunggyo; Lee, Kyubum; Yu, Namhee; Jang, Insu; Choi, Ikjung; Kim, Pora; Jang, Ye Eun; Kim, Byounggun; Kim, Sunkyu; Lee, Byungwook; Kang, Jaewoo; Lee, Sanghyuk

    2017-01-04

    Fusion gene is an important class of therapeutic targets and prognostic markers in cancer. ChimerDB is a comprehensive database of fusion genes encompassing analysis of deep sequencing data and manual curations. In this update, the database coverage was enhanced considerably by adding two new modules of The Cancer Genome Atlas (TCGA) RNA-Seq analysis and PubMed abstract mining. ChimerDB 3.0 is composed of three modules of ChimerKB, ChimerPub and ChimerSeq. ChimerKB represents a knowledgebase including 1066 fusion genes with manual curation that were compiled from public resources of fusion genes with experimental evidences. ChimerPub includes 2767 fusion genes obtained from text mining of PubMed abstracts. ChimerSeq module is designed to archive the fusion candidates from deep sequencing data. Importantly, we have analyzed RNA-Seq data of the TCGA project covering 4569 patients in 23 cancer types using two reliable programs of FusionScan and TopHat-Fusion. The new user interface supports diverse search options and graphic representation of fusion gene structure. ChimerDB 3.0 is available at http://ercsb.ewha.ac.kr/fusiongene/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Reducing Cancer Health Disparities through Community Engagement: Working with Faith-Based Organizations (Project CHURCH) | Division of Cancer Prevention

    Science.gov (United States)

    Speaker | "Reducing Cancer Health Disparities through Community Engagement: Working with Faith-Based Organizations (Project CHURCH)" will be presented by Lorna H. McNeill, PhD, MPH, Chair of the Department of Health Disparities at the University of Texas MD Anderson Cancer Center in Houston, TX. Date: 2/20/2018; Time: 11:00am - 12:00pm; Location: NCI Shady Grove Campus,

  19. NME2 reduces proliferation, migration and invasion of gastric cancer cells to limit metastasis.

    Directory of Open Access Journals (Sweden)

    Yan-fei Liu

    Full Text Available Gastric cancer is one of the most common malignancies and has a high rate of metastasis. We hypothesize that NME2 (Nucleoside Diphosphate Kinase 2, which has previously been considered as an anti-metastatic gene, plays a role in the invasiveness of gastric cancer cells. Using a tissue chip technology and immunohistochemistry, we demonstrated that NME2 expression was associated with levels of differentiation of gastric cancer cells and their metastasis into the lymph nodes. When the NME2 gene product was over-expressed by ;in vitro stable transfection, cells from BGC823 and MKN45 gastric cancer cell lines had reduced rates of proliferation, migration, and invasion through the collagen matrix, suggesting an inhibitory activity of NME2 in the propagation and invasion of gastric cancer. NME2 could, therefore, severe as a risk marker for gastric cancer invasiveness and a potential new target for gene therapy to enhance or induce NME2 expression.

  20. Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer

    Science.gov (United States)

    2015-10-01

    RHOB, RRAS, RHOA, PLAU, RHOF, ITGB5, ITGB3 Methylglyoxal degradation III 2.17Eþ00 1.30E01 AKR1C1/AKR1C2, AKR1C3, AKR1C4 Dopamine degradation...2007;25: 2921–7. 6. Bober SL, Recklitis CJ, Bakan J, Garber JE, Patenaude AF. Addressing sexual dysfunction after risk-reducing salpingo-oophorectomy

  1. Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer

    Science.gov (United States)

    2017-12-01

    removed by Picard Tools, and base quality score recalibration and Indel (insert/deletion) realignment using the Genome Analysis Toolkit GATK (McKenna et...Analysis Toolkit : a MapReduce framework for analyzing next-generation DNA sequencing data. Genome research 20, 1297-1303. McLean, C. Y., Bristor, D...CA151683), a Department of Defense Career Development award (CA130247), and grants from Gabrielle’s Angel Foundation and Concern Foundation. GGW is also

  2. External beam radiotherapy (EBRT) techniques used in breast cancer treatment to reduce cardiac exposure

    International Nuclear Information System (INIS)

    Fung, Esther; Hendry, Julie

    2013-01-01

    Radiotherapy in breast cancer treatment has been shown to reduce local recurrence and improve survival rates. However, there is a concern that breast radiotherapy can cause an increase in cardiac mortality, particularly in patients being treated for left-sided breast cancer. This review aims to investigate how cardiac exposure is minimised in breast radiotherapy and determine an optimal method for reducing cardiac dose, using literature from ScienceDirect, Medline and CINAHL. IMRT and breathing-adapted radiotherapy both reduce cardiac exposure but IMRT also increases the irradiated volume at low dose. Several issues were reported with regards to the clinical implementation of these techniques. It is suggested that inspiration breath-hold radiotherapy, is the preferred solution to minimising cardiac exposure but more research is warranted to confirm this. Long-term follow-up is required to determine dose–response relationships. Research needs to focus on breast cancer treatment as a whole in order to effectively reduce cardiac mortality.

  3. Reduced expression of p27 is a novel mechanism of docetaxel resistance in breast cancer cells

    International Nuclear Information System (INIS)

    Brown, Iain; Shalli, Kawan; McDonald, Sarah L; Moir, Susan E; Hutcheon, Andrew W; Heys, Steven D; Schofield, Andrew C

    2004-01-01

    Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. However, apoptosis and cell cycle regulation are key mechanisms by which most chemotherapeutic agents exert their cytotoxic effects. We created two docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) and performed cDNA microarray analysis to identify candidate genes associated with docetaxel resistance. Gene expression changes were validated at the RNA and protein levels by reverse transcription PCR and western analysis, respectively. Gene expression cDNA microarray analysis demonstrated reduced p27 expression in docetaxel-resistant breast cancer cells. Although p27 mRNA expression was found to be reduced only in MCF-7 docetaxel-resistant sublines (2.47-fold), reduced expression of p27 protein was noted in both MCF-7 and MDA-MB-231 docetaxel-resistant breast cancer cells (2.83-fold and 3.80-fold, respectively). This study demonstrates that reduced expression of p27 is associated with acquired resistance to docetaxel in breast cancer cells. An understanding of the genes that are involved in resistance to chemotherapy may allow further development in modulating drug resistance, and may permit selection of those patients who are most likely to benefit from such therapies

  4. Transcriptome-wide studies of prostate cancer cell lines in the context of medical radiation; Transkriptomweite Untersuchungen von Prostata-Krebszelllinien im Kontext medizinischer Strahlentherapie

    Energy Technology Data Exchange (ETDEWEB)

    Hammer, Paul

    2012-06-26

    The use of radiotherapy in addition to chemotherapy and surgical removal is the most powerful instrument in the fight against malignant tumors in cancer medicine. After cardiovascular diseases, cancer is the second leading cause of death in the western world, in which prostate cancer is the most frequent male cancer. Despite continuous technological improvements in radiological instruments and prognosis, it may occur a recurrence up to many years after radiotherapy due to a high resistance capability of individual malignant cells of the locally occurring tumor. Although modern radiation biology has studied many aspects of the resistance mechanisms, questions are largely unanswered especially in regards to prognostic terms and time response of tumor cells to ionizing radiation. As cellular models four prostate cancer cell lines with different radiation sensitivities (PC3, DuCaP, DU-145, RWPE-1) were cultured and tested for their ability to survive after exposure to ionizing radiation by a trypane blue and MTT viability assay. The proliferative capacity of the four cell lines was determined using a colony formation assay. The PC3 cell line (radiation-resistant) and the DuCaP cell line (radiation-sensitive) showed the maximal differences in terms of radiation sensitivity. Based on these results the two cell lines were selected to allow identification of potential prognostic marker for predicting the effectiveness of radiation therapy via their transcriptome-wide gene expression. Furthermore, a time series experiment with the radiation-resistant PC3 cell line was performed. At 8 different time points, during the period from 00:00 - 42:53 (hh:mm) after exposure with 1 Gy, the mRNA was quantified by next generation sequencing to investigate the dynamic behavior of time-delayed gene expression and to discover resistance mechanisms. Of 10,966 expressed genes 730 were significant differentially expressed, determined by setting a fold change threshold in conjunction with a P

  5. Cancer Pain Management Education Rectifies Patients' Misconceptions of Cancer Pain, Reduces Pain, and Improves Quality of Life.

    Science.gov (United States)

    Koh, Su-Jin; Keam, Bhumsuk; Hyun, Min Kyung; Ju Seo, Jeong; Uk Park, Keon; Oh, Sung Yong; Ahn, Jinseok; Lee, Ja Youn; Kim, JinShil

    2018-03-26

    More than half of the patients have reported improper management of breakthrough cancer pain. Empirical evidence is lacking concerning the effectiveness of cancer pain education on breakthrough pain control. This study aimed to examine the effects of individual pain education on pain control, use of short-acting analgesics for breakthrough pain, quality of life outcomes, and rectification of patients' misconceptions regarding cancer pain. A quasi-experimental design was used. In total, 176 (102 inpatients and 74 outpatients) and 163 (93 inpatients and 70 outpatients) cancer patients completed questionnaires on pain intensity, quality of life, use of short-acting medication for breakthrough pain, and misconceptions about cancer pain and opioid use before and immediately and/or seven days after individual pain education. The mean age of the participants was 60.9 years (±11.2), and 56.3% were male. The most common cancers were lung cancer (17.0%), colon cancer (15.9%), and breast cancer (12.5%). The subjects' reasons for attrition were conditional deterioration, death, or voluntary withdrawal (N = 13, 7.4%). Following the education, there was a significant reduction in overall pain intensity over 24 hours (P < 0.001). The outpatients showed more use of short-acting analgesics for breakthrough pain. Sleep quality change was most significantly associated with intervention; other quality of life aspects (e.g., general feelings and life enjoyment) also improved. Pain education also significantly reduced misconceptions regarding cancer pain management. The present educational intervention was effective in encouraging short-acting analgesic use for breakthrough pain, improving quality of life outcomes, and rectifying patients' misconceptions about analgesic use.

  6. The generation and utilization of a cancer-oriented representation of the human transcriptome by using expressed sequence tags

    DEFF Research Database (Denmark)

    Brentani, Helena; Caballero, Otávia L; Camargo, Anamaria A

    2003-01-01

    expressed sequence tags (ESTs) from human tumors and their corresponding normal tissues in the public databases. The data currently define approximately 23,500 genes, of which only approximately 1,250 are still represented only by ESTs. Examination of the EST coverage of known cancer-related (CR) genes...... reveals that ESTs, indicating that the representation of genes associated with commonly studied tumors is high. The careful recording of the origin of all ESTs we have produced has enabled detailed definition of where the genes they represent are expressed in the human body....... More than 100,000 ESTs are available for seven tissues, indicating a surprising variability of gene usage that has led to the discovery of a significant number of genes with restricted expression, and that may thus be therapeutically useful. The ESTs also reveal novel nonsynonymous germline variants...

  7. Hormones and breast cancer: can we use them in ways that could reduce the risk?

    Directory of Open Access Journals (Sweden)

    Khalid Mahmud

    2011-12-01

    Full Text Available Many hormones promote or inhibit breast cancer in different ways. These effects and the mechanisms involved are reviewed in order to suggest a potentially safer use of hormones. Natural estrogens, administered transdermally, and natural progesterone may be the safest combination of female hormones. Increased intake of cruciferous vegetables could provide additional safety by improving 2-hydoxyestrone and diminishing 16 alphahydroxyestrone. Testosterone and dehydroepiandrosterone (DHEA may directly inhibit breast cancer, but could potentially stimulate it by being aromatized into estrogen in the breast. Modest doses with blood level monitoring appear logical. Melatonin and oxytocin are inhibitory to breast and other cancers. Insulin is a growth factor for breast cancer. Managing insulin resistance before the onset of diabetes could reduce the risk. Tri-iodothyronine (T3 has multiple anti-breast cancer effects. Synthroid may not increase T3 levels adequately. Human growth hormone does not appear to increase risk; but it should not be given for performance enhancement.

  8. Update on raloxifene: role in reducing the risk of invasive breast cancer in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Vogel VG

    2011-10-01

    Full Text Available Victor G Vogel Cancer Institute, Geisinger Health System, Danville, PA, USA Abstract: Risk factors allow us to define women who are at increased lifetime risk for breast cancer, and the most important factor is age. Benign breast disease increases risk, and the most important histologies are atypical lobular or ductal hyperplasia and lobular carcinoma in situ. Family history of breast cancer among first-degree relatives (mother, sisters, daughters also increases risk. Quantitative measures of risk give accurate predictions of breast cancer incidence for groups of women but not for individual subjects. Multiple published, randomized controlled trials, which employed selective estrogen receptor (ER modulators (SERMs, have demonstrated consistent reductions of 35% or greater in the risk of ER-positive invasive and noninvasive breast cancer in postmenopausal women. Professional organizations in the US now recommend the use of SERMs to reduce the risk of breast cancer in high-risk, postmenopausal women. Raloxifene and tamoxifen reduce the risk of ER-positive invasive breast cancer with equal efficacy, but raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in breast cancer risk from either agent translates into reduced breast cancer mortality. Overall quality of life is similar with raloxifene or tamoxifen, but the incidence of dyspareunia, weight gain, and musculoskeletal complaints is higher with raloxifene use, whereas vasomotor symptoms, bladder incontinence, gynecologic symptoms, and leg cramps were higher with tamoxifen use. Keywords: selective estrogen receptor modulators (SERMs, raloxifene, risk reduction, chemoprevention

  9. A novel approach to breast cancer prevention: reducing excessive ovarian androgen production in elderly women.

    Science.gov (United States)

    Secreto, Giorgio; Sieri, Sabina; Agnoli, Claudia; Grioni, Sara; Muti, Paola; Zumoff, Barnett; Sant, Milena; Meneghini, Elisabetta; Krogh, Vittorio

    2016-08-01

    Minimizing endogenous estrogen production and activity in women at high risk for breast cancer is a prominent approach to prevention of the disease. A number of clinical trials have shown that the administration of selective-estrogen receptor modulators or aromatase inhibitors significantly reduces the incidence of breast cancer in healthy women. Unfortunately, these drugs often produce adverse effects on the quality of life and are, therefore, poorly accepted by many women, even those who are at high risk for breast cancer. We propose a novel alternative approach to decreasing estrogen production: suppression of ovarian synthesis of the androgen precursors of estrogens by administration of long-acting gonadotropin-releasing hormone analogs to women with ovarian stromal hyperplasia. The specific target population would be elderly postmenopausal women, at increased risk of breast cancer, and with high blood levels of testosterone, marker of ovarian hyperandrogenemia, and recognized factor of risk for breast cancer. Testosterone levels are measured at baseline to identify women at risk and during the follow-up to evaluate the effectiveness of therapy. The postmenopausal ovary is an important source of excessive androgen production which originates from the ovarian interstitial cell hyperplasia frequently present in breast cancer patients. We propose to counter the source of androgen excess in women with ovarian stromal hyperplasia, thus reducing the substrate for estrogen formation without completely inhibiting estrogen synthesis. Available evidence indicates that gonadotropin-releasing hormone analogs can be safely used for breast cancer prevention in postmenopausal women.

  10. Web services for transcriptomics

    NARCIS (Netherlands)

    Neerincx, P.

    2009-01-01

    Transcriptomics is part of a family of disciplines focussing on high throughput molecular biology experiments. In the case of transcriptomics, scientists study the expression of genes resulting in transcripts. These transcripts can either perform a biological function themselves or function as

  11. An expert system design to diagnose cancer by using a new method reduced rule base.

    Science.gov (United States)

    Başçiftçi, Fatih; Avuçlu, Emre

    2018-04-01

    A Medical Expert System (MES) was developed which uses Reduced Rule Base to diagnose cancer risk according to the symptoms in an individual. A total of 13 symptoms were used. With the new MES, the reduced rules are controlled instead of all possibilities (2 13 = 8192 different possibilities occur). By controlling reduced rules, results are found more quickly. The method of two-level simplification of Boolean functions was used to obtain Reduced Rule Base. Thanks to the developed application with the number of dynamic inputs and outputs on different platforms, anyone can easily test their own cancer easily. More accurate results were obtained considering all the possibilities related to cancer. Thirteen different risk factors were determined to determine the type of cancer. The truth table produced in our study has 13 inputs and 4 outputs. The Boolean Function Minimization method is used to obtain less situations by simplifying logical functions. Diagnosis of cancer quickly thanks to control of the simplified 4 output functions. Diagnosis made with the 4 output values obtained using Reduced Rule Base was found to be quicker than diagnosis made by screening all 2 13 = 8192 possibilities. With the improved MES, more probabilities were added to the process and more accurate diagnostic results were obtained. As a result of the simplification process in breast and renal cancer diagnosis 100% diagnosis speed gain, in cervical cancer and lung cancer diagnosis rate gain of 99% was obtained. With Boolean function minimization, less number of rules is evaluated instead of evaluating a large number of rules. Reducing the number of rules allows the designed system to work more efficiently and to save time, and facilitates to transfer the rules to the designed Expert systems. Interfaces were developed in different software platforms to enable users to test the accuracy of the application. Any one is able to diagnose the cancer itself using determinative risk factors. Thereby

  12. Reduced mitochondrial DNA content associates with poor prognosis of prostate cancer in African American men.

    Directory of Open Access Journals (Sweden)

    Shahriar Koochekpour

    Full Text Available Reduction or depletion of mitochondrial DNA (mtDNA has been associated with cancer progression. Although imbalanced mtDNA content is known to occur in prostate cancer, differences in mtDNA content between African American (AA and Caucasian American (CA men are not defined. We provide the first evidence that tumors in AA men possess reduced level of mtDNA compared to CA men. The median tumor mtDNA content was reduced in AA men. mtDNA content was also reduced in normal prostate tissues of AA men compared to CA men, suggesting a possible predisposition to cancer in AA men. mtDNA content was also reduced in benign prostatic hyperplasia (BPH tissue from AA men. Tumor and BPH tissues from patients ≥ 60 years of age possess reduced mtDNA content compared to patients 7 compared to ≤ 7, whereas reduced mtDNA content was observed in tumors of Gleason grade >7 compared to ≤ 7. Together, our data suggest that AA men possess lower mtDNA levels in normal and tumor tissues compared to CA men, which could contribute to higher risk and more aggressive prostate cancer in AA men.

  13. Reduced mitochondrial DNA content associates with poor prognosis of prostate cancer in African American men.

    Science.gov (United States)

    Koochekpour, Shahriar; Marlowe, Timothy; Singh, Keshav K; Attwood, Kristopher; Chandra, Dhyan

    2013-01-01

    Reduction or depletion of mitochondrial DNA (mtDNA) has been associated with cancer progression. Although imbalanced mtDNA content is known to occur in prostate cancer, differences in mtDNA content between African American (AA) and Caucasian American (CA) men are not defined. We provide the first evidence that tumors in AA men possess reduced level of mtDNA compared to CA men. The median tumor mtDNA content was reduced in AA men. mtDNA content was also reduced in normal prostate tissues of AA men compared to CA men, suggesting a possible predisposition to cancer in AA men. mtDNA content was also reduced in benign prostatic hyperplasia (BPH) tissue from AA men. Tumor and BPH tissues from patients ≥ 60 years of age possess reduced mtDNA content compared to patients 7 compared to ≤ 7, whereas reduced mtDNA content was observed in tumors of Gleason grade >7 compared to ≤ 7. Together, our data suggest that AA men possess lower mtDNA levels in normal and tumor tissues compared to CA men, which could contribute to higher risk and more aggressive prostate cancer in AA men.

  14. Subtotal Colectomy for Colon Cancer Reduces the Need for Subsequent Surgery in Lynch Syndrome.

    Science.gov (United States)

    Renkonen-Sinisalo, Laura; Seppälä, Toni T; Järvinen, Heikki J; Mecklin, Jukka-Pekka

    2017-08-01

    The risk of metachronous colorectal cancer is high after surgical resection for first colon cancer in Lynch syndrome. This study aimed to examine whether extended surgery decreases the risk of subsequent colorectal cancer and improves long-term survival. This was a retrospective study. Data were collected from a nationwide registry. Two hundred forty-two Lynch syndrome pathogenic variant carriers who underwent surgery for a first colon cancer from 1984 to 2009 were included. Patients underwent standard segmental colectomy (n = 144) or extended colectomy (n = 98) for colon cancer. Patients were followed a median of 14.6 up to 25 years. Risk of subsequent colorectal cancer in either group, overall and disease-specific survival, and operative mortality were the primary outcomes measured. Subtotal colectomy decreased the risk of subsequent colorectal cancer (HR, 0.20; 95% CI, 0.08-0.52; p = 0.001), compared with segmental resection. Subsequent colorectal cancer decreased in MLH1 carriers. The MSH2 carriers showed no statistical difference, possibly because of their small number. Disease-specific and overall survival within 25 years did not differ between the standard and extended surgeries (82.7% vs 87.2%, p = 0.76 and 47.2% vs 41.4%, p = 0.83). The cumulative risk of subsequent colorectal cancer was 20% in 10 years and 47% within 25 years after standard resection and 4% and 9% after extended surgery. The cumulative risk of metachronous colorectal cancer was 7% within 25 years after subtotal colectomy with ileosigmoidal anastomosis. One patient died of postoperative septicemia within 30 days after segmental colectomy. Data on surgical procedures were primarily collected retrospectively. Lynch syndrome pathogenic variant carriers may undergo subtotal colectomy to manage first colon cancer and avoid repetitive abdominal surgery and to reduce the remaining bowel to facilitate easier endoscopic surveillance. It provides no survival benefit, compared with segmental colon

  15. Simulation of reduced breast cancer mortality in breast cancer screening programs

    International Nuclear Information System (INIS)

    Zamora, L. I.; Forastero, C.; Guirado, D.; Lallena, A. M.

    2011-01-01

    The breast cancer screening programs are an essential tool in the fight against breast cancer. Currently, many questions concerning the setup of these programs are open, namely: age range of women who undergo the same, frequency of mammography, ... The effectiveness of a program should be evaluated in terms of mortality reduction is its systematic implementation in the population. In this sense, we performed Monte Carlo simulations to assess that these reductions.

  16. Downregulation of CD44 reduces doxorubicin resistance of CD44+CD24- breast cancer cells

    Directory of Open Access Journals (Sweden)

    Phuc PV

    2011-06-01

    Full Text Available Pham Van Phuc, Phan Lu Chinh Nhan, Truong Hai Nhung, Nguyen Thanh Tam, Nguyen Minh Hoang, Vuong Gia Tue, Duong Thanh Thuy, Phan Kim NgocLaboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh, VietnamBackground: Cells within breast cancer stem cell populations have been confirmed to have a CD44+CD24- phenotype. Strong expression of CD44 plays a critical role in numerous types of human cancers. CD44 is involved in cell differentiation, adhesion, and metastasis of cancer cells.Methods: In this study, we reduced CD44 expression in CD44+CD24- breast cancer stem cells and investigated their sensitivity to an antitumor drug. The CD44+CD24- breast cancer stem cells were isolated from breast tumors; CD44 expression was downregulated with siRNAs followed by treatment with different concentrations of the antitumor drug.Results: The proliferation of CD44 downregulated CD44+CD24- breast cancer stem cells was decreased after drug treatment. We noticed treated cells were more sensitive to doxorubicin, even at low doses, compared with the control groups.Conclusions: It would appear that expression of CD44 is integral among the CD44+CD24- cell population. Reducing the expression level of CD44, combined with doxorubicin treatment, yields promising results for eradicating breast cancer stem cells in vitro. This study opens a new direction in treating breast cancer through gene therapy in conjunction with chemotherapy.Keywords: antitumor drugs, breast cancer stem cells, CD44, CD44+CD24- cells, doxorubicin

  17. Muscle mass as a target to reduce fatigue in patients with advanced cancer.

    Science.gov (United States)

    Neefjes, Elisabeth C W; van den Hurk, Renske M; Blauwhoff-Buskermolen, Susanne; van der Vorst, Maurice J D L; Becker-Commissaris, Annemarie; de van der Schueren, Marian A E; Buffart, Laurien M; Verheul, Henk M W

    2017-08-01

    Cancer-related fatigue (CRF) reduces quality of life and the activity level of patients with cancer. Cancer related fatigue can be reduced by exercise interventions that may concurrently increase muscle mass. We hypothesized that low muscle mass is directly related to higher CRF. A total of 233 patients with advanced cancer starting palliative chemotherapy for lung, colorectal, breast, or prostate cancer were studied. The skeletal muscle index (SMI) was calculated as the patient's muscle mass on level L3 or T4 of a computed tomography scan, adjusted for height. Fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-fatigue questionnaire (cut-off for fatigue fatigue score was 36 (interquartile range 26-44). A higher SMI on level L3 was significantly associated with less CRF for men (B 0.447, P 0.004) but not for women (B - 0.401, P 0.090). No association between SMI on level T4 and the Functional Assessment of Chronic Illness Therapy-fatigue score was found (n = 82). The association between SMI and CRF may lead to the suggestion that male patients may be able to reduce fatigue by exercise interventions aiming at an increased muscle mass. In women with advanced cancer, CRF is more influenced by other causes, because it is not significantly related to muscle mass. To further reduce CRF in both men and women with cancer, multifactorial assessments need to be performed in order to develop effective treatment strategies. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

  18. Risk-reducing mastectomy for the prevention of primary breast cancer.

    Science.gov (United States)

    Carbine, Nora E; Lostumbo, Liz; Wallace, Judi; Ko, Henry

    2018-04-05

    Recent progress in understanding the genetic basis of breast cancer and widely publicized reports of celebrities undergoing risk-reducing mastectomy (RRM) have increased interest in RRM as a method of preventing breast cancer. This is an update of a Cochrane Review first published in 2004 and previously updated in 2006 and 2010. (i) To determine whether risk-reducing mastectomy reduces death rates from any cause in women who have never had breast cancer and in women who have a history of breast cancer in one breast, and (ii) to examine the effect of risk-reducing mastectomy on other endpoints, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes. For this Review update, we searched Cochrane Breast Cancer's Specialized Register, MEDLINE, Embase and the WHO International Clinical Trials Registry Platform (ICTRP) on 9 July 2016. We included studies in English. Participants included women at risk for breast cancer in at least one breast. Interventions included all types of mastectomy performed for the purpose of preventing breast cancer. At least two review authors independently abstracted data from each report. We summarized data descriptively; quantitative meta-analysis was not feasible due to heterogeneity of study designs and insufficient reporting. We analyzed data separately for bilateral risk-reducing mastectomy (BRRM) and contralateral risk-reducing mastectomy (CRRM). Four review authors assessed the methodological quality to determine whether or not the methods used sufficiently minimized selection bias, performance bias, detection bias, and attrition bias. All 61 included studies were observational studies with some methodological limitations; randomized trials were absent. The studies presented data on 15,077 women with a wide range of risk factors for breast cancer, who underwent RRM.Twenty-one BRRM studies looking at the incidence of breast cancer or disease-specific mortality, or

  19. The diabetes medication Canagliflozin reduces cancer cell proliferation by inhibiting mitochondrial complex-I supported respiration

    Directory of Open Access Journals (Sweden)

    Linda A. Villani

    2016-10-01

    Full Text Available Objective: The sodium-glucose transporter 2 (SGLT2 inhibitors Canagliflozin and Dapagliflozin are recently approved medications for type 2 diabetes. Recent studies indicate that SGLT2 inhibitors may inhibit the growth of some cancer cells but the mechanism(s remain unclear. Methods: Cellular proliferation and clonogenic survival were used to assess the sensitivity of prostate and lung cancer cell growth to the SGLT2 inhibitors. Oxygen consumption, extracellular acidification rate, cellular ATP, glucose uptake, lipogenesis, and phosphorylation of AMP-activated protein kinase (AMPK, acetyl-CoA carboxylase, and the p70S6 kinase were assessed. Overexpression of a protein that maintains complex-I supported mitochondrial respiration (NDI1 was used to establish the importance of this pathway for mediating the anti-proliferative effects of Canagliflozin. Results: Clinically achievable concentrations of Canagliflozin, but not Dapagliflozin, inhibit cellular proliferation and clonogenic survival of prostate and lung cancer cells alone and in combination with ionizing radiation and the chemotherapy Docetaxel. Canagliflozin reduced glucose uptake, mitochondrial complex-I supported respiration, ATP, and lipogenesis while increasing the activating phosphorylation of AMPK. The overexpression of NDI1 blocked the anti-proliferative effects of Canagliflozin indicating reductions in mitochondrial respiration are critical for anti-proliferative actions. Conclusion: These data indicate that like the biguanide metformin, Canagliflozin not only lowers blood glucose but also inhibits complex-I supported respiration and cellular proliferation in prostate and lung cancer cells. These observations support the initiation of studies evaluating the clinical efficacy of Canagliflozin on limiting tumorigenesis in pre-clinical animal models as well epidemiological studies on cancer incidence relative to other glucose lowering therapies in clinical populations. Keywords: AMP

  20. Reduced incidence of lung cancer in patients with idiopathic pulmonary fibrosis treated with pirfenidone.

    Science.gov (United States)

    Miura, Yukiko; Saito, Takefumi; Tanaka, Toru; Takoi, Hiroyuki; Yatagai, Yohei; Inomata, Minoru; Nei, Takahito; Saito, Yoshinobu; Gemma, Akihiko; Azuma, Arata

    2018-01-01

    Idiopathic pulmonary fibrosis (IPF) is a disease with a worse prognosis than some types of cancer. In patients with IPF, lung cancer is critical because of the associated high mortality rate from its progression and fatal complications from anticancer treatments. Therefore, preventing lung cancer in patients with IPF is primordial. Pirfenidone is an anti-fibrotic agent that reduces the decline in forced vital capacity. This study aimed to assess the effect of pirfenidone in the development of lung cancer in patients with IPF. Data from 261 patients with IPF with and without pirfenidone were retrospectively reviewed, and the incidence of lung cancer was analyzed. In the pirfenidone group, the incidence of lung cancer was significantly lower than in the non-pirfenidone group (2.4% vs. 22.0%, P < 0.0001). Multivariate Cox proportional hazards regression analysis demonstrated that pirfenidone decreased the risk of lung cancer (hazard ratio, 0.11; 95% confidence interval, 0.03 to 0.46; P = 0.003), whereas coexisting emphysema increased the incidence of lung cancer (hazard ratio, 3.22; 95% confidence interval, 1.35 to 7.70; P = 0.009). Pirfenidone might correlate with a decreased risk of lung cancer in patients with IPF. However, no definite conclusion can be drawn from this retrospective study, and a multicenter, prospective cohort study is still warranted to confirm the effect of pirfenidone on lung cancer in patients with IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

  1. Is cancer survivorship associated with reduced work engagement? A NOCWO Study.

    Science.gov (United States)

    Berg Gudbergsson, Saevar; Fosså, Sophie D; Dahl, Alv A

    2008-09-01

    This study explores work engagement in employed tumor-free cancer survivors (CSs) compared to matched controls from the general population (NORM). The sample consisted of 446 CSs tumor-free after primary treatment [226 females with breast cancer and 220 males (166 testicular cancer and 54 prostate cancer)] diagnosed 2-6 years prior to the study. All had returned to work and had favourable prognosis. NORM sample consisted of 588 employed controls (319 females, 269 males). All CSs and NORM filled in a mailed questionnaire covering demography, morbidity, and work-related issues including work engagement which was self-rated by the Utrecht Work Engagement Scale (UWES). No differences in work engagement were observed between the CSs and NORM measured by the UWES total scale score or by the Dedication and Absorption domain scores. The Vigor domains score was statistically lower among CSs (p = .03), but the effect size was only 0.19. The CSs reported significantly poorer work ability, poorer health status, greater numbers of disease symptoms, more anxiety, and reduced physical quality of life, and scored significantly higher on both neuroticism and extraversion. CONCLUSIONS/IMPLICATIONS FOR CSS: In spite of poorer health CSs who had returned to work after their treatment for breast, prostate, and testicular cancer showed similar work engagement as individuals without cancer. In such CSs employers have no reason to expect reduced work engagement. Future research should preferably have a prospective and comparative design.

  2. Reduced risk of axillary lymphatic spread in triple-negative breast cancer

    DEFF Research Database (Denmark)

    Holm-Rasmussen, Emil Villiam; Jensen, Maj-Britt; Balslev, Eva

    2015-01-01

    We examined the association between the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status of women with primary breast cancer and the risk of axillary lymph node (ALN) involvement at the time of diagnosis. Information on 20,009 women diagnosed with primary breast...... cancer between 2008 and 2012 was retrieved from the Danish Breast Cancer Cooperative Group database. The associations between clinical and pathological variables and ALN involvement at the time of diagnosis were evaluated in univariate and multivariate regression analyses, as well as the significance......-negative breast cancer (TNBC) patients showed a significantly reduced risk of ALN involvement at the time of diagnosis compared to patients with HR-positive/HER2-negative tumors (OR 0.55; 95 % CI 0.49-0.62; P

  3. Reduced employment and financial hardship among middle-aged individuals with colorectal cancer.

    Science.gov (United States)

    Gordon, Louisa G; Beesley, Vanessa L; Mihala, Gabor; Koczwara, Bogda; Lynch, Brigid M

    2017-09-01

    Financial hardship may affect up to 30% of cancer survivors, however, little research has addressed the effect of employment change on financial hardship. This study compared the self-reported financial hardship of middle-aged (45-64 years) colorectal cancer survivors (n = 187) at 6 and 12 months following diagnosis with that of a matched general population group (n = 355). Colorectal cancer survivors were recruited through the Queensland Cancer Registry, Australia; data from the Household Income and Labour Dynamics in Australia (HILDA) Survey were used for the general population group. Pearson chi-square tests were used to assess the differences in proportions between the two groups and McNemar tests to assess differences across time among the same group. Generalised linear modelling was performed to produce prevalence ratios. A higher proportion of workers with colorectal cancer reported financial strain (money shortage for living essentials) at 6 months (15%) but eased and was comparable to the comparison group at 12 months (7%). Middle-aged working cancer survivors who ceased or reduced work were more likely to report not being financially comfortable, compared with those who had continued work (adjusted prevalence ratio 1.66, 95%CI: 1.12, 2.44) at 12 months. Health professionals, employers and government services should address the impact of impaired employment on financial hardship among cancer survivors. © 2017 John Wiley & Sons Ltd.

  4. Microsatellite instability is associated with reduced disease specific survival in stage III colon cancer.

    Science.gov (United States)

    Mohan, H M; Ryan, E; Balasubramanian, I; Kennelly, R; Geraghty, R; Sclafani, F; Fennelly, D; McDermott, R; Ryan, E J; O'Donoghue, D; Hyland, J M P; Martin, S T; O'Connell, P R; Gibbons, D; Winter, Des; Sheahan, K

    2016-11-01

    Up to 15% of colorectal cancers exhibit microsatellite instability (MSI), where errors in replication go unchecked due to defects in the mismatch repair system. This study aimed to determine survival in a large single-centre series of 1250 consecutive colorectal cancers subjected to universal MSI testing. Clinical and pathological features of patients with colorectal cancer identified on prospectively maintained colorectal and pathology databases at St. Vincent's University Hospital from 2004 to May 2012 were examined. Mismatch repair (MMR) status was determined by immunohistochemistry. Kaplan-Meier curves, the log-rank test and Cox regression were used to associate survival with clinical and pathological characteristics. Of the 1250 colorectal cancers in the study period, 11% exhibited MSI (n = 138). Patients with MSI tumours had significantly lower rates of lymph node and distant metastases (MSI N+ rate: 24.8% compared with MSS N+ rate: 46.2%, p colon cancer. However, patients with Stage III MSI colon cancers had a worse DSS than those with MSS tumours. Stage III MSI tumours exhibited higher rates of lymphovascular invasion and perineural invasion than Stage I/II MSI tumours. MSI is associated with a reduced risk of nodal and distant metastases, with an improved DSS in Stage I/II colon cancer. However, when MSI tumours progress to Stage III these patients had worse outcomes and pathological features. New strategies for this cohort of patients may be required to improve outcomes. Copyright © 2016. Published by Elsevier Ltd.

  5. Hepatoma targeting peptide conjugated bio-reducible polymer complexed with oncolytic adenovirus for cancer gene therapy.

    Science.gov (United States)

    Choi, Joung-Woo; Kim, Hyun Ah; Nam, Kihoon; Na, Youjin; Yun, Chae-Ok; Kim, SungWan

    2015-12-28

    Despite adenovirus (Ad) vector's numerous advantages for cancer gene therapy, such as high ability of endosomal escape, efficient nuclear entry mechanism, and high transduction, and therapeutic efficacy, tumor specific targeting and antiviral immune response still remain as a critical challenge in clinical setting. To overcome these obstacles and achieve cancer-specific targeting, we constructed tumor targeting bioreducible polymer, an arginine grafted bio-reducible polymer (ABP)-PEG-HCBP1, by conjugating PEGylated ABP with HCBP1 peptides which has high affinity and selectivity towards hepatoma. The ABP-PEG-HCBP1-conjugated replication incompetent GFP-expressing ad, (Ad/GFP)-ABP-PEG-HCBP1, showed a hepatoma cancer specific uptake and transduction compared to either naked Ad/GFP or Ad/GFP-ABP. Competition assays demonstrated that Ad/GFP-ABP-PEG-HCBP1-mediated transduction was specifically inhibited by HCBP1 peptide rather than coxsackie and adenovirus receptor specific antibody. In addition, ABP-PEG-HCBP1 can protect biological activity of Ad against serum, and considerably reduced both innate and adaptive immune response against Ad. shMet-expressing oncolytic Ad (oAd; RdB/shMet) complexed with ABP-PEG-HCBP1 delivered oAd efficiently into hepatoma cancer cells. The oAd/ABP-PEG-HCBP1 demonstrated enhanced cancer cell killing efficacy in comparison to oAd/ABP complex. Furthermore, Huh7 and HT1080 cancer cells treated with oAd/shMet-ABP-PEG-HCBP1 complex had significantly decreased Met and VEGF expression in hepatoma cancer, but not in non-hepatoma cancer. In sum, these results suggest that HCBP1-conjugated bioreducible polymer could be used to deliver oncolytic Ad safely and efficiently to treat hepatoma. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Culturally-Relevant Online Cancer Education Modules Empower Alaska's Community Health Aides/Practitioners to Disseminate Cancer Information and Reduce Cancer Risk.

    Science.gov (United States)

    Cueva, Katie; Revels, Laura; Cueva, Melany; Lanier, Anne P; Dignan, Mark; Viswanath, K; Fung, Teresa T; Geller, Alan C

    2017-04-12

    To address a desire for timely, medically accurate cancer education in rural Alaska, ten culturally relevant online learning modules were developed with, and for, Alaska's Community Health Aides/Practitioners (CHA/Ps). The project was guided by the framework of Community-Based Participatory Action Research, honored Indigenous Ways of Knowing, and was informed by Empowerment Theory. A total of 428 end-of-module evaluation surveys were completed by 89 unique Alaska CHA/Ps between January and December 2016. CHA/Ps shared that as a result of completing the modules, they were empowered to share cancer information with their patients, families, friends, and communities, as well as engage in cancer risk reduction behaviors such as eating healthier, getting cancer screenings, exercising more, and quitting tobacco. CHA/Ps also reported the modules were informative and respectful of their diverse cultures. These results from end-of-module evaluation surveys suggest that the collaboratively developed, culturally relevant, online cancer education modules have empowered CHA/Ps to reduce cancer risk and disseminate cancer information. "brought me to tears couple of times, and I think it will help in destroying the silence that surrounds cancer".

  7. Polymorphisms of XRCC4 are involved in reduced colorectal cancer risk in Chinese schizophrenia patients

    Directory of Open Access Journals (Sweden)

    Li Tao

    2010-10-01

    Full Text Available Abstract Background Genetic factors related to the regulation of apoptosis in schizophrenia patients may be involved in a reduced vulnerability to cancer. XRCC4 is one of the potential candidate genes associated with schizophrenia which might induce colorectal cancer resistance. Methods To examine the genetic association between colorectal cancer and schizophrenia, we analyzed five SNPs (rs6452526, rs2662238, rs963248, rs35268, rs2386275 covering ~205.7 kb in the region of XRCC4. Results We observed that two of the five genetic polymorphisms showed statistically significant differences between 312 colorectal cancer subjects without schizophrenia and 270 schizophrenia subjects (rs6452536, p = 0.004, OR 0.61, 95% CI 0.44-0.86; rs35268, p = 0.028, OR 1.54, 95% CI 1.05-2.26. Moreover, the haplotype which combined all five markers was the most significant, giving a global p = 0.0005. Conclusions Our data firstly indicate that XRCC4 may be a potential protective gene towards schizophrenia, conferring reduced susceptibility to colorectal cancer in the Han Chinese population.

  8. Breast cancer screening in BRCA1 and BRCA2 mutation carriers after risk reducing salpingo-oophorectomy

    NARCIS (Netherlands)

    Fakkert, I.E.; Jansen, L.; Meijer, K.; Kok, Theo; Oosterwijk, J.C.; Mourits, M.J.E.; de Bock, G.H.

    Breast cancer screening is offered to BRCA1 and BRCA2 mutation carriers from the age of 25 years because of their increased risk of breast cancer. As ovarian cancer screening is not effective, risk-reducing salpingho-oophorectomy (RRSO) is offered after child bearing age. RRSO before menopause

  9. Adherence of Primary Care Physicians to Evidence-Based Recommendations to Reduce Ovarian Cancer Mortality

    Science.gov (United States)

    Stewart, Sherri L.; Townsend, Julie S.; Puckett, Mary C.; Rim, Sun Hee

    2017-01-01

    Ovarian cancer is the deadliest gynecologic cancer. Receipt of treatment from a gynecologic oncologist is an evidence-based recommendation to reduce mortality from the disease. We examined knowledge and application of this evidence-based recommendation in primary care physicians as part of CDC gynecologic cancer awareness campaign efforts and discussed results in the context of CDC National Comprehensive Cancer Control Program (NCCCP). We analyzed primary care physician responses to questions about how often they refer patients diagnosed with ovarian cancer to gynecologic oncologists, and reasons for lack of referral. We also analyzed these physicians’ knowledge of tests to help determine whether a gynecologic oncologist is needed for a planned surgery. The survey response rate was 52.2%. A total of 84% of primary care physicians (87% of family/general practitioners, 81% of internists and obstetrician/gynecologists) said they always referred patients to gynecologic oncologists for treatment. Common reasons for not always referring were patient preference or lack of gynecologic oncologists in the practice area. A total of 23% of primary care physicians had heard of the OVA1 test, which helps to determine whether gynecologic oncologist referral is needed. Although referral rates reported here are high, it is not clear whether ovarian cancer patients are actually seeing gynecologic oncologists for care. The NCCCP is undertaking several efforts to assist with this, including education of the recommendation among women and providers and assistance with treatment summaries and patient navigation toward appropriate treatment. Expansion of these efforts to all populations may help improve adherence to recommendations and reduce ovarian cancer mortality. PMID:26978124

  10. Mindfulness practice reduces cortisol blunting during chemotherapy: A randomized controlled study of colorectal cancer patients.

    Science.gov (United States)

    Black, David S; Peng, Cheng; Sleight, Alix G; Nguyen, Nathalie; Lenz, Heinz-Josef; Figueiredo, Jane C

    2017-08-15

    The objective of this randomized clinical experiment was to test the influence of a mindfulness meditation practice, when delivered during 1 session of active chemotherapy administration, on the acute salivary cortisol response as a marker of neuroendocrine system activity in cancer patients. A mindfulness, attention-control, or resting exposure was assigned to 57 English- or Spanish-speaking colorectal cancer patients at 1 county oncology clinic and 1 university oncology clinic at the start of chemotherapy. Saliva samples were collected at the start of chemotherapy and at subsequent 20-minute intervals during the first 60 minutes of chemotherapy (4 samples in all). Self-reporting on biobehavioral assessments after chemotherapy included distress, fatigue, and mindfulness. An area-under-the-curve analysis (AUC) showed a relative increase in cortisol reactivity in the mindfulness group after adjustments for biological and clinical measures (β = 123.21; P = .03). More than twice as many patients in the mindfulness group versus the controls displayed a cortisol rise from the baseline to 20 minutes (69% vs 34%; P = .02). AUC values were uncorrelated with biobehavioral measure scores, although mindfulness scores were inversely correlated with fatigue (r = -0.46; P mindfulness practice during chemotherapy can reduce the blunting of neuroendocrine profiles typically observed in cancer patients. Implications include support for the use of mindfulness practice in integrative oncology. Cancer 2017;123:3088-96. © 2017 American Cancer Society. © 2017 American Cancer Society.

  11. Reduced incidence of skin cancer in patients with alopecia areata: A retrospective cohort study.

    Science.gov (United States)

    Mostaghimi, Arash; Qureshi, Sarah; Joyce, Cara; Guo, Ye; Huang, Kathie P

    2016-04-01

    The risk of skin cancer in patients with alopecia areata (AA) is unknown. While the risk of skin cancer in chronic inflammatory alopecias may be elevated, AA shares many characteristics with vitiligo, an autoimmune illness associated with decreased risk of melanoma and non-melanoma skin cancers. In this retrospective cohort study, we determined the risk of developing skin cancer among patients with AA in a validated cohort relative to matched controls at two tertiary care hospitals in Massachusetts. There was a significantly decreased risk of NMSC in AA patients than controls (OR=0.63, 95% CI=0.48-0.81). There was a trend towards a protective effect of AA associated with melanoma (OR=0.65, 95% CI=0.39-1.09). There was no difference in anatomic distribution of skin cancer between patients with AA and controls. Our study demonstrates a decreased risk of nonmelanoma skin cancer and a trend towards reduced risk of melanoma in patients with AA. Copyright © 2016. Published by Elsevier Ltd.

  12. Free Base Lysine Increases Survival and Reduces Metastasis in Prostate Cancer Model.

    Science.gov (United States)

    Ibrahim-Hashim, Arig; Wojtkowiak, Jonathan W; de Lourdes Coelho Ribeiro, Maria; Estrella, Veronica; Bailey, Kate M; Cornnell, Heather H; Gatenby, Robert A; Gillies, Robert J

    2011-11-19

    Malignant tumor cells typically metabolize glucose anaerobically to lactic acid even under normal oxygen tension, a phenomenon called aerobic glycolysis or the Warburg effect. This results in increased acid production and the acidification of the extracellular microenvironment in solid tumors. H + ions tend to flow along concentration gradients into peritumoral normal tissue causing extracellular matrix degradation and increased tumor cell motility thus promoting invasion and metastasis. We have shown that reducing this acidity with sodium bicarbonate buffer decreases the metastatic fitness of circulating tumor cells in prostate cancer and other cancer models. Mathematical models of the tumor-host dynamics predicted that buffers with a pka around 7 will be more effective in reducing intra- and peri-tumoral acidosis and, thus, and possibly more effective in inhibiting tumor metastasis than sodium bicarbonate which has a pKa around 6. Here we test this prediction the efficacy of free base lysine; a non-bicarbonate/non-volatile buffer with a higher pKa (~10), on prostate tumor metastases model. Oxygen consumption and acid production rate of PC3M prostate cancer cells and normal prostate cells were determined using the Seahorse Extracellular Flux (XF-96) analyzer. In vivo effect of 200 mM lysine started four days prior to inoculation on inhibition of metastasis was examined in PC3M-LUC-C6 prostate cancer model using SCID mice. Metastases were followed by bioluminescence imaging. PC3M prostate cancer cells are highly acidic in comparison to a normal prostate cell line indicating that reduction of intra- and perit-tumoral acidosis should inhibit metastases formation. In vivo administration of 200 mM free base lysine increased survival and reduced metastasis. PC3M prostate cancer cells are highly glycolytic and produce large amounts of acid when compared to normal prostate cells. Administration of non-volatile buffer decreased growth of metastases and improved survival

  13. Information Framing Reduces Initial Negative Attitudes in Cancer Patients' Decisions About Hospice Care.

    Science.gov (United States)

    Fridman, Ilona; Glare, Paul A; Stabler, Stacy M; Epstein, Andrew S; Wiesenthal, Alison; Leblanc, Thomas W; Higgins, E Tory

    2018-06-01

    Negative attitudes toward hospice care might prevent patients with cancer from discussing and choosing hospice as they approach end of life. When making a decision, people often naturally focus on either expected benefits or the avoidance of harm. Behavioral research has demonstrated that framing information in an incongruent manner with patients' underlying motivational focus reduces their negative attitudes toward a disliked option. Our study tests this communication technique with cancer patients, aiming to reduce negative attitudes toward a potentially beneficial but often-disliked option, that is, hospice care. Patients (n = 42) with active cancer of different types and/or stages completed a paper survey. Participants read a vignette about a patient with advanced cancer and a limited prognosis. In the vignette, the physician's advice to enroll in a hospice program was randomized, creating a congruent message or an incongruent message with patients' underlying motivational focus (e.g., a congruent message for someone most interested in benefits focuses on the benefits of hospice, whereas an incongruent message for this patient focuses on avoiding harm). Patients' attitudes toward hospice were measured before and after receiving the physician's advice. Regression analyses indicated that information framing significantly influenced patients with strong initial negative attitudes. Patients were more likely to reduce intensity of their initial negative attitude about hospice when receiving an incongruent message (b = -0.23; P negative reactions toward hospice care. Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  14. Soya and isoflavone intakes associated with reduced risk of oesophageal cancer in north-west China.

    Science.gov (United States)

    Tang, Li; Lee, Andy H; Xu, Fenglian; Zhang, Taotao; Lei, Jun; Binns, Colin W

    2015-01-01

    To ascertain the association between soya consumption, isoflavone intakes and oesophageal cancer risk in remote north-west China, where the incidence of oesophageal cancer is known to be high. Case-control study. Information on habitual consumption of soya foods and soya milk was obtained by personal interview. The intakes of isoflavones were then estimated using the US Department of Agriculture nutrient database. Logistic regression analyses were performed to assess the association between soya consumption, isoflavone intakes and oesophageal cancer risk. Urumqi and Shihezi, Xinjiang Uyghur Autonomous Region, China. Participants were 359 incident oesophageal cancer patients and 380 hospital-based controls. The oesophageal cancer patients consumed significantly less (P soya foods (mean 57·2 (sd 119·0) g/d) and soya milk (mean 18·8 (sd 51·7) ml/d) than the controls (mean 93·3 (sd 121·5) g/d and mean 35·7 (sd 73·0) ml/d). Logistic regression analyses showed an inverse association between intake of soya products and the risk of oesophageal cancer. The adjusted odds were OR = 0·33 (95 % CI 0·22, 0·49) and OR = 0·48 (95 % CI 0·31, 0·74) for consuming at least 97 g of soya foods and 60 ml of soya milk daily (the highest tertiles of consumption), respectively, relative to the lowest tertiles of consumption. Similarly, inverse associations with apparent dose-response relationships were found between isoflavone intakes and oesophageal cancer risk. Habitual consumption of soya products appears to be associated with reduced risk of oesophageal cancer in north-west China.

  15. Metformin reduces thyroid cancer risk in Taiwanese patients with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Chin-Hsiao Tseng

    Full Text Available BACKGROUND: Whether metformin may affect thyroid cancer risk has not been studied. This study investigated the association between metformin use and thyroid cancer risk in Taiwanese patients with type 2 diabetes mellitus. METHODS: The reimbursement databases of all diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and 1,414,723 patients with type 2 diabetes were followed for thyroid cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of metformin exposure using tertile cutoffs for cumulative duration of therapy and cumulative dose were calculated and adjusted hazard ratios were estimated by Cox regression. Additional sensitivity analyses were conducted. RESULTS: There were 795,321 ever-users and 619,402 never-users, with respective numbers of incident thyroid cancer of 683 (0.09% and 1,614 (0.26%, and respective incidence of 24.09 and 87.33 per 100,000 person-years. The overall fully adjusted hazard ratio (95% confidence interval was 0.683 (0.598-0.780, and all categories of the dose-response parameters showed significantly lower risk with P-trends < 0.0001. The protective effect of metformin on thyroid cancer incidence was also supported by sensitivity analyses, disregarding age (< 50 or ≥ 50 years and sex; and was not affected by excluding users of insulin, sulfonylurea, and insulin and/or sulfonylurea respectively, by previous diagnosis of other cancers or by potential detection examinations that might lead to differential diagnosis of thyroid cancer. CONCLUSIONS: This study provides evidence for the first time that metformin use in patients with type 2 diabetes may reduce the risk of thyroid cancer.

  16. Health Care Coach Support in Reducing Acute Care Use and Cost in Patients With Cancer

    Science.gov (United States)

    2017-05-12

    Acute Myeloid Leukemia; Brain Glioblastoma; Estrogen Receptor Negative; Extensive Stage Small Cell Lung Carcinoma; Head and Neck Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Limited Stage Small Cell Lung Carcinoma; Myelodysplastic Syndrome; Progesterone Receptor Negative; Progressive Disease; Recurrent Carcinoma; Stage II Pancreatic Cancer; Stage II Rectal Cancer; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIC Rectal Cancer; Stage III Colon Cancer; Stage III Esophageal Cancer; Stage III Gastric Cancer; Stage III Non-Small Cell Lung Cancer; Stage III Ovarian Cancer; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Skin Melanoma; Stage IIIA Colon Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Rectal Cancer; Stage IIIA Skin Melanoma; Stage IIIB Colon Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Rectal Cancer; Stage IIIB Skin Melanoma; Stage IIIC Colon Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Rectal Cancer; Stage IIIC Skin Melanoma; Stage IV Bladder Cancer; Stage IV Bone Sarcoma; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Esophageal Cancer; Stage IV Gastric Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Renal Cell Cancer; Stage IV Skin Melanoma; Stage IV Soft Tissue Sarcoma; Stage IVA Bone Sarcoma; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Bone Sarcoma; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Triple-Negative Breast Carcinoma

  17. O-Linked β-N-Acetylglucosaminylation (O-GlcNAcylation) in Primary and Metastatic Colorectal Cancer Clones and Effect of N-Acetyl-β-d-glucosaminidase Silencing on Cell Phenotype and Transcriptome*

    Science.gov (United States)

    Yehezkel, Galit; Cohen, Liz; Kliger, Adi; Manor, Esther; Khalaila, Isam

    2012-01-01

    O-Linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is a regulatory post-translational modification occurring on the serine or threonine residues of nucleocytoplasmic proteins. O-GlcNAcylation is dynamically regulated by O-GlcNAc transferase and O-GlcNAcase (OGA), which are responsible for O-GlcNAc addition and removal, respectively. Although O-GlcNAcylation was found to play a significant role in several pathologies such as type II diabetes and neurodegenerative diseases, the role of O-GlcNAcylation in the etiology and progression of cancer remains vague. Here, we followed O-GlcNAcylation and its catalytic machinery in metastatic clones of human colorectal cancer and the effect of OGA knockdown on cellular phenotype and on the transcriptome. The colorectal cancer SW620 metastatic clone exhibited increased O-GlcNAcylation and decreased OGA expression compared with its primary clone, SW480. O-GlcNAcylation elevation in SW620 cells, through RNA interference of OGA, resulted in phenotypic alterations that included acquisition of a fibroblast-like morphology, which coincides with epithelial metastatic progression and growth retardation. Microarray analysis revealed that OGA silencing altered the expression of about 1300 genes, mostly involved in cell movement and growth, and specifically affected metabolic pathways of lipids and carbohydrates. These findings support the involvement of O-GlcNAcylation in various aspects of tumor cell physiology and suggest that this modification may serve as a link between metabolic changes and cancer. PMID:22730328

  18. Next-generation transcriptome assembly

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Jeffrey A.; Wang, Zhong

    2011-09-01

    Transcriptomics studies often rely on partial reference transcriptomes that fail to capture the full catalog of transcripts and their variations. Recent advances in sequencing technologies and assembly algorithms have facilitated the reconstruction of the entire transcriptome by deep RNA sequencing (RNA-seq), even without a reference genome. However, transcriptome assembly from billions of RNA-seq reads, which are often very short, poses a significant informatics challenge. This Review summarizes the recent developments in transcriptome assembly approaches - reference-based, de novo and combined strategies-along with some perspectives on transcriptome assembly in the near future.

  19. Resveratrol Reduces Prostate Cancer Growth and Metastasis by Inhibiting the Akt/MicroRNA-21 Pathway

    Science.gov (United States)

    Sheth, Sandeep; Jajoo, Sarvesh; Kaur, Tejbeer; Mukherjea, Debashree; Sheehan, Kelly; Rybak, Leonard P.; Ramkumar, Vickram

    2012-01-01

    The consumption of foods containing resveratrol produces significant health benefits. Resveratrol inhibits cancer by reducing cell proliferation and metastasis and by inducing apoptosis. These actions could be explained by its ability to inhibit (ERK-1/2), Akt and suppressing the levels of estrogen and insulin growth factor -1 (IGF-1) receptor. How these processes are manifested into the antitumor actions of resveratrol is not clear. Using microarray studies, we show that resveratrol reduced the expression of various prostate-tumor associated microRNAs (miRs) including miR-21 in androgen-receptor negative and highly aggressive human prostate cancer cells, PC-3M-MM2. This effect of resveratrol was associated with reduced cell viability, migration and invasiveness. Additionally, resveratrol increased the expression of tumor suppressors, PDCD4 and maspin, which are negatively regulated by miR-21. Short interfering (si) RNA against PDCD4 attenuated resveratrol’s effect on prostate cancer cells, and similar effects were observed following over expression of miR-21 with pre-miR-21 oligonucleotides. PC-3M-MM2 cells also exhibited high levels of phospho-Akt (pAkt), which were reduced by both resveratrol and LY294002 (a PI3-kinase inhibitor). MiR-21 expression in these cells appeared to be dependent on Akt, as LY294002 reduced the levels of miR-21 along with a concurrent increase in PDCD4 expression. These in vitro findings were further corroborated in a severe combined immunodeficient (SCID) mouse xenograft model of prostate cancer. Oral administration of resveratrol not only inhibited the tumor growth but also decreased the incidence and number of metastatic lung lesions. These tumor- and metastatic-suppressive effects of resveratrol were associated with reduced miR-21 and pAkt, and elevated PDCD4 levels. Similar anti-tumor effects of resveratrol were observed in DU145 and LNCaP prostate cancer cells which were associated with suppression of Akt and PDCD4, but

  20. Evaluating sexual nursing care intervention for reducing sexual dysfunction in Indonesian cervical cancer survivors

    Directory of Open Access Journals (Sweden)

    Yati Afiyanti

    2016-01-01

    Full Text Available Objective: This study aims to describe the factors affecting successful nursing care intervention on sexuality. Methods: A one-group pre- and post-test design was used. Fifty-three cervical cancer survivors and their spouses were administered with nursing care intervention on sexuality in three sessions and evaluated after 6 weeks. Results: Sexual intervention reduced dyspareunia symptoms, improved vaginal lubrication, improved sexual satisfaction, and enhanced sexual arousal, sexual desire, and orgasm among cancer survivors and their spouses. The other influencing factors also simultaneously contributed to the success of nursing care intervention. Conclusions: Nursing care intervention on sexuality could be a part of supportive nursing care and an important aspect in standard nursing care for cancer patients in Indonesia.

  1. Endometrial cancer - reduce to the minimum. A new paradigm for adjuvant treatments?

    International Nuclear Information System (INIS)

    Scheithauer, Heike R; Schulz, Diana S; Belka, Claus

    2011-01-01

    Up to now, the role of adjuvant radiation therapy and the extent of lymph node dissection for early stage endometrial cancer are controversial. In order to clarify the current position of the given adjuvant treatment options, a systematic review was performed. Both, Pubmed and ISI Web of Knowledge database were searched using the following keywords and MESH headings: 'Endometrial cancer', 'Endometrial Neoplasms', 'Endometrial Neoplasms/radiotherapy', 'External beam radiation therapy', 'Brachytherapy' and adequate combinations. Recent data from randomized trials indicate that external beam radiation therapy - particularly in combination with extended lymph node dissection - or radical lymph node dissection increases toxicity without any improvement of overall survival rates. Thus, reduced surgical aggressiveness and limitation of radiotherapy to vaginal-vault-brachytherapy only is sufficient for most cases of early stage endometrial cancer

  2. Meta-analysis: Does garlic intake reduce risk of gastric cancer?

    Science.gov (United States)

    Kodali, R T; Eslick, Guy D

    2015-01-01

    In the past 2 decades, various epidemiological studies investigated whether garlic can positively modify the risk of gastric cancer. Garlic contains numerous sulfide compounds, including diallyl trisulfide, which have anticarcinogenic properties. We conducted a meta-analysis to determine if garlic intake reduces the risk of gastric cancer. An electronic search of MEDLINE, PubMed, and EMBASE to June 2014 was completed. There were 14 case control studies, 2 randomized controlled studies, and 1 cohort study that fulfilled our inclusion criteria. We used a random effects model to calculate pooled odds ratios (OR) and 95% confidence intervals (CIs) for risk of gastric cancer with garlic consumption. Meta-analysis of a total of 8,621 cases and 14,889 controls was conducted. Significant variability in duration of garlic intake and reference categories for amount of intake was noted. High, low, and any garlic intake were all associated with reduced risk of gastric cancer. High intake had the most significant risk reduction, OR = 0.49 (95% CI: 0.38-0.62). Heterogeneity was low (I² = 30.85, P = 0.17). A more modest risk reduction was associated with low intake, OR = 0.75 (95% CI: 0.58-0.97). Half of the studies did not separate garlic intake into high or low amounts, intake was only noted as consumption vs. non-consumption. Any amount of consumption still showed a risk reduction similar to low intake, OR = 0.77 (95% CI: 0.60-1.00). Low and any amount of consumption showed moderate heterogeneity (58% and 45%, respectively). Garlic intake appears to be associated with reduced risk of gastric cancer. Further high quality studies are required to confirm this finding and to assess the amount of garlic that needs to be consumed for protective effect.

  3. Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice.

    Science.gov (United States)

    Comish, Paul B; Drumond, Ana Luiza; Kinnell, Hazel L; Anderson, Richard A; Matin, Angabin; Meistrich, Marvin L; Shetty, Gunapala

    2014-01-01

    Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT) and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP) is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1) mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2%) and to 80% in the male offspring of L1 (control value 33%). These increases are similar to those observed in both lines of mice by radiation. In utero exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼ 70% of control and induced atrophic seminiferous tubules in ∼ 30% of the testes. When the in utero CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i) DNA damage is a common mechanism leading to induction of testicular cancer, ii) increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii) children exposed to radiation or DNA damaging chemotherapeutic agents in utero may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan.

  4. Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice.

    Directory of Open Access Journals (Sweden)

    Paul B Comish

    Full Text Available Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1 mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2% and to 80% in the male offspring of L1 (control value 33%. These increases are similar to those observed in both lines of mice by radiation. In utero exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼ 70% of control and induced atrophic seminiferous tubules in ∼ 30% of the testes. When the in utero CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i DNA damage is a common mechanism leading to induction of testicular cancer, ii increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii children exposed to radiation or DNA damaging chemotherapeutic agents in utero may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan.

  5. Reduced lung cancer mortality in dairy farmers: is endotoxin exposure the key factor?

    Science.gov (United States)

    Mastrangelo, G; Marzia, V; Marcer, G

    1996-11-01

    From two areas in the Province of Padova, we selected 2,283 male farmers who worked either in cattle raising or in crop/orchard cultivation. There were 422 cohort deaths from 1970 to 1992. Using the regional population as a reference, the standardized mortality ratio (SMR) was calculated, with 95% confidence intervals (CI) based on the Poisson distribution. Cancer mortality was significantly reduced among the 1,561 dairy farmers (SMR = 0.65; CI = 0.53-0.81); there was a significant decrease in lung cancer (SMR = 0.49; CI = 0.31-0.74), whereas a significant increase from brain tumors was found (SMR = 2.83; CI = 1.04-6.17). Neither overall cancer mortality nor the lung cancer SMR deviated significantly from unity for the 722 crop/orchard farmers. Among dairy farmers, moreover, lung cancer SMRs showed a significant downward trend across the quartiles of increasing length of work, 0.96 in the first quartile, and 0.48, 0.40, and 0.25 in the second, third, and fourth quartiles, respectively. Moreover, lung cancer risk decreased with increasing farm land area, with SMRs in the quartiles of 0.89, 0.37, 0.41 and 0.19. This decrease cannot be attributed to either a selection (healthy worker effect) or a confounding (lower percentage of smokers) bias. Nor was it due to an artifact introduced by differences in age distribution among the quartiles. Dairy farmers are known to be exposed to higher airborne endotoxin concentrations; reasonably, this cumulative exposure increases further with years of work and area of farm. Endotoxins may have protected the dairy farmers against lung cancer through the tumor necrosis factor produced by alveolar macrophages.

  6. Communication strategies to reduce cancer disparities: Insights from African-American mother-daughter dyads.

    Science.gov (United States)

    Mosavel, Maghboeba; Wilson Genderson, Maureen; Ports, Katie A; Carlyle, Kellie E

    2015-12-01

    Mothers and daughters share a powerful and unique bond, which has potential for the dissemination of information on a variety of women's health issues, including the primary and secondary prevention of breast and cervical cancer. This study presents formative research from a long-term project examining the potential of mother-daughter communication in promoting cancer screening among African American women. Thirty-two mother-daughter pairs (N = 64) completed orally administered surveys regarding their cancer knowledge, beliefs and attitudes, and barriers to care. This study compares the attitudes and beliefs of low-income, urban, African American mothers and their adolescent daughters regarding cervical and breast cancer screening. Both mothers and daughters had fairly high levels of knowledge about breast and cervical cancer. In addition, there was a high concordance rate between mothers' and daughters' responses, suggesting a potential sharing of health knowledge between mother and daughter. These results have implications for selecting communication strategies to reduce health disparities, and support that the mother-daughter dyad could be a viable unit to disseminate targeted screening information. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

  7. Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells.

    Science.gov (United States)

    Hummon, Amanda B; Pitt, Jason J; Camps, Jordi; Emons, Georg; Skube, Susan B; Huppi, Konrad; Jones, Tamara L; Beissbarth, Tim; Kramer, Frank; Grade, Marian; Difilippantonio, Michael J; Ried, Thomas; Caplen, Natasha J

    2012-01-04

    Colorectal carcinomas (CRC) carry massive genetic and transcriptional alterations that influence multiple cellular pathways. The study of proteins whose loss-of-function (LOF) alters the growth of CRC cells can be used to further understand the cellular processes cancer cells depend upon for survival. A small-scale RNAi screen of ~400 genes conducted in SW480 CRC cells identified several candidate genes as required for the viability of CRC cells, most prominently CASP8AP2/FLASH. To understand the function of this gene in maintaining the viability of CRC cells in an unbiased manner, we generated gene specific expression profiles following RNAi. Silencing of CASP8AP2/FLASH resulted in altered expression of over 2500 genes enriched for genes associated with cellular growth and proliferation. Loss of CASP8AP2/FLASH function was significantly associated with altered transcription of the genes encoding the replication-dependent histone proteins as a result of the expression of the non-canonical polyA variants of these transcripts. Silencing of CASP8AP2/FLASH also mediated enrichment of changes in the expression of targets of the NFκB and MYC transcription factors. These findings were confirmed by whole transcriptome analysis of CASP8AP2/FLASH silenced cells at multiple time points. Finally, we identified and validated that CASP8AP2/FLASH LOF increases the expression of neurofilament heavy polypeptide (NEFH), a protein recently linked to regulation of the AKT1/ß-catenin pathway. We have used unbiased RNAi based approaches to identify and characterize the function of CASP8AP2/FLASH, a protein not previously reported as required for cell survival. This study further defines the role CASP8AP2/FLASH plays in the regulating expression of the replication-dependent histones and shows that its LOF results in broad and reproducible effects on the transcriptome of colorectal cancer cells including the induction of expression of the recently described tumor suppressor gene NEFH.

  8. Preeclampsia-Associated Hormonal Profiles and Reduced Breast Cancer Risk Among Older Mothers

    Science.gov (United States)

    2003-04-01

    Preeclampsia has been linked to reduced breast cancer risk, and this reduction may be especially marked among women who bear their first child later...in life. In this ongoing case-control study, we examine the hormonal profiles of older Colorado mothers with and without a history of preeclampsia in...premenopausal, and are free of serious chronic disease. Cases are 14 Denver area women who experienced preeclampsia in their first pregnancy; controls are 13

  9. A psychoeducational intervention reduces the need for anesthesia during radiotherapy for young childhood cancer patients

    International Nuclear Information System (INIS)

    Haeberli, Sonja; Grotzer, Michael A; Niggli, Felix K; Landolt, Markus A; Linsenmeier, Claudia; Ammann, Roland A; Bodmer, Nicole

    2008-01-01

    Radiotherapy (RT) has become an important treatment modality in pediatric oncology, but its delivery to young children with cancer is challenging and general anesthesia is often needed. To evaluate whether a psychoeducational intervention might reduce the need for anesthesia, 223 consecutive pediatric cancer patients receiving 4141 RT fractions during 244 RT courses between February 1989 and January 2006 were studied. Whereas in 154 RT courses corresponding with 2580 RT fractions patients received no psychoeducational intervention (group A), 90 RT courses respectively 1561 RT fractions were accomplished by using psychoeducational intervention (group B). This tailored psychoeducational intervention in group B included a play program and interactive support by a trained nurse according to age to get familiar with staff, equipment and procedure of radiotherapy. Group A did not differ significantly from group B in age at RT, gender, diagnosis, localization of RT and positioning during RT. Whereas 33 (21.4%) patients in group A got anesthesia, only 8 (8.9%) patients in group B needed anesthesia. The median age of cooperating patients without anesthesia decreased from 3.2 to 2.7 years. In both uni- and multivariate analyses the psychoeducational intervention significantly and independently reduced the need for anesthesia. We conclude that a specifically tailored psychoeducational intervention is able to reduce the need for anesthesia in children undergoing RT for cancer. This results in lower costs and increased cooperation during RT

  10. A psychoeducational intervention reduces the need for anesthesia during radiotherapy for young childhood cancer patients

    Directory of Open Access Journals (Sweden)

    Linsenmeier Claudia

    2008-06-01

    Full Text Available Abstract Background Radiotherapy (RT has become an important treatment modality in pediatric oncology, but its delivery to young children with cancer is challenging and general anesthesia is often needed. Methods To evaluate whether a psychoeducational intervention might reduce the need for anesthesia, 223 consecutive pediatric cancer patients receiving 4141 RT fractions during 244 RT courses between February 1989 and January 2006 were studied. Whereas in 154 RT courses corresponding with 2580 RT fractions patients received no psychoeducational intervention (group A, 90 RT courses respectively 1561 RT fractions were accomplished by using psychoeducational intervention (group B. This tailored psychoeducational intervention in group B included a play program and interactive support by a trained nurse according to age to get familiar with staff, equipment and procedure of radiotherapy. Results Group A did not differ significantly from group B in age at RT, gender, diagnosis, localization of RT and positioning during RT. Whereas 33 (21.4% patients in group A got anesthesia, only 8 (8.9% patients in group B needed anesthesia. The median age of cooperating patients without anesthesia decreased from 3.2 to 2.7 years. In both uni- and multivariate analyses the psychoeducational intervention significantly and independently reduced the need for anesthesia. Conclusion We conclude that a specifically tailored psychoeducational intervention is able to reduce the need for anesthesia in children undergoing RT for cancer. This results in lower costs and increased cooperation during RT.

  11. Reduced metastasis of transgenic mammary cancer in urokinase-deficient mice

    DEFF Research Database (Denmark)

    Almholt, Kasper; Lund, L.R.; Rygaard, Jørgen

    2005-01-01

    A prominent phenotype of plasmin deficiency in mice is reduced metastasis in the MMTV-PymT transgenic breast cancer model. Proteolytically active plasmin is generated from inactive plasminogen by one of 2 activators, uPA or tPA. We now find that uPA deficiency alone significantly reduces metastasis...... >7-fold in the MMTV-PymT model. We studied a cohort of 55 MMTV-PymT transgenic mice, either uPA-deficient or wild-type controls. Tumor incidence, latency, growth rate and final primary tumor burden were not significantly affected by uPA deficiency. In contrast, average lung metastasis volume...

  12. Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

    Directory of Open Access Journals (Sweden)

    Flores Juana M

    2010-07-01

    Full Text Available Abstract Background ErbB2-positive breast cancer is characterized by highly aggressive phenotypes and reduced responsiveness to standard therapies. Although specific ErbB2-targeted therapies have been designed, only a small percentage of patients respond to these treatments and most of them eventually relapse. The existence of this population of particularly aggressive and non-responding or relapsing patients urges the search for novel therapies. The purpose of this study was to determine whether cannabinoids might constitute a new therapeutic tool for the treatment of ErbB2-positive breast tumors. We analyzed their antitumor potential in a well established and clinically relevant model of ErbB2-driven metastatic breast cancer: the MMTV-neu mouse. We also analyzed the expression of cannabinoid targets in a series of 87 human breast tumors. Results Our results show that both Δ9-tetrahydrocannabinol, the most abundant and potent cannabinoid in marijuana, and JWH-133, a non-psychotropic CB2 receptor-selective agonist, reduce tumor growth, tumor number, and the amount/severity of lung metastases in MMTV-neu mice. Histological analyses of the tumors revealed that cannabinoids inhibit cancer cell proliferation, induce cancer cell apoptosis, and impair tumor angiogenesis. Cannabinoid antitumoral action relies, at least partially, on the inhibition of the pro-tumorigenic Akt pathway. We also found that 91% of ErbB2-positive tumors express the non-psychotropic cannabinoid receptor CB2. Conclusions Taken together, these results provide a strong preclinical evidence for the use of cannabinoid-based therapies for the management of ErbB2-positive breast cancer.

  13. Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer cell growth.

    Science.gov (United States)

    Mukhopadhyay, Archana; Hanold, Laura E; Thayele Purayil, Hamsa; Gisemba, Solomon A; Senadheera, Sanjeewa N; Aldrich, Jane V

    2017-08-03

    The oncoprotein c-Myc is often overexpressed in cancer cells, and the stability of this protein has major significance in deciding the fate of a cell. Thus, targeting c-Myc levels is an attractive approach for developing therapeutic agents for cancer treatment. In this study, we report the anti-cancer activity of the macrocyclic peptides [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) and the natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]). [D-Trp]CJ-15,208 reduced c-Myc protein levels in prostate cancer cells and decreased cell proliferation with IC 50 values ranging from 2.0 to 16 µM in multiple PC cell lines. [D-Trp]CJ-15,208 induced early and late apoptosis in PC-3 cells following 48 hours treatment, and growth arrest in the G2 cell cycle phase following both 24 and 48 hours treatment. Down regulation of c-Myc in PC-3 cells resulted in loss of sensitivity to [D-Trp]CJ-15,208 treatment, while overexpression of c-Myc in HEK-293 cells imparted sensitivity of these cells to [D-Trp]CJ-15,208 treatment. This macrocyclic tetrapeptide also regulated PP2A by reducing the levels of its phosphorylated form which regulates the stability of cellular c-Myc protein. Thus [D-Trp]CJ-15,208 represents a new lead compound for the potential development of an effective treatment of prostate cancer.

  14. A Healthy Dietary Pattern Reduces Lung Cancer Risk: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yanlai Sun

    2016-03-01

    Full Text Available Background: Diet and nutrients play an important role in cancer development and progress; a healthy dietary pattern has been found to be associated with several types of cancer. However, the association between a healthy eating pattern and lung cancer risk is still unclear. Objective: Therefore, we conducted a systematic review with meta-analysis to evaluate whether a healthy eating pattern might reduce lung cancer risk. Methods: We identified relevant studies from the PubMed and Embase databases up to October 2015, and the relative risks were extracted and combined by the fixed-effects model when no substantial heterogeneity was observed; otherwise, the random-effects model was employed. Subgroup and publication bias analyses were also performed. Results: Finally, eight observational studies were included in the meta-analysis. The pooled relative risk of lung cancer for the highest vs. lowest category of healthy dietary pattern was 0.81 (95% confidence interval, CI: 0.75–0.86, and no significant heterogeneity was detected. The relative risks (RRs for non-smokers, former smokers and current smokers were 0.89 (95% CI: 0.63–1.27, 0.74 (95% CI: 0.62–0.89 and 0.86 (95% CI: 0.79–0.93, respectively. The results remained stable in subgroup analyses by other confounders and sensitivity analysis. Conclusions: The results of our meta-analysis suggest that a healthy dietary pattern is associated with a lower lung cancer risk, and they provide more beneficial evidence for changing the diet pattern in the general population.

  15. A Healthy Dietary Pattern Reduces Lung Cancer Risk: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Sun, Yanlai; Li, Zhenxiang; Li, Jianning; Li, Zengjun; Han, Jianjun

    2016-03-04

    Diet and nutrients play an important role in cancer development and progress; a healthy dietary pattern has been found to be associated with several types of cancer. However, the association between a healthy eating pattern and lung cancer risk is still unclear. Therefore, we conducted a systematic review with meta-analysis to evaluate whether a healthy eating pattern might reduce lung cancer risk. We identified relevant studies from the PubMed and Embase databases up to October 2015, and the relative risks were extracted and combined by the fixed-effects model when no substantial heterogeneity was observed; otherwise, the random-effects model was employed. Subgroup and publication bias analyses were also performed. Finally, eight observational studies were included in the meta-analysis. The pooled relative risk of lung cancer for the highest vs. lowest category of healthy dietary pattern was 0.81 (95% confidence interval, CI: 0.75-0.86), and no significant heterogeneity was detected. The relative risks (RRs) for non-smokers, former smokers and current smokers were 0.89 (95% CI: 0.63-1.27), 0.74 (95% CI: 0.62-0.89) and 0.86 (95% CI: 0.79-0.93), respectively. The results remained stable in subgroup analyses by other confounders and sensitivity analysis. The results of our meta-analysis suggest that a healthy dietary pattern is associated with a lower lung cancer risk, and they provide more beneficial evidence for changing the diet pattern in the general population.

  16. Red wine consumption not associated with reduced risk of colorectal cancer.

    Science.gov (United States)

    Chao, Chun; Haque, Reina; Caan, Bette J; Poon, Kwun-Yee T; Tseng, Hung-Fu; Quinn, Virginia P

    2010-01-01

    Red wine contains polyphenol antioxidants that inhibit colorectal cancer (CRC) development in animal studies. We investigated the effect of red wine intake on risk of CRC in the California Men's Health Study (CMHS). CMHS is a prospective, multiethnic cohort of middle-aged men who were members of the Kaiser Permanente (KP) California Health Plans and completed study questionnaires between 2002-2003. Incident CRC were identified from the health plan cancer registries through the end of 2007 (n = 287). To properly account for potential confounding by previous endoscopy screening, we restricted the primary analyses to CMHS men continuously enrolled in KP between 1998-2002 (n = 43,483 and CRC = 176). We used multivariable Cox regression to adjust for important confounders. We did not find an inverse association between moderate red wine intake and risk of CRC. The hazard ratio for consuming >/=1 drink/day (average = 2 drinks/day) was 1.16, 95% confidence intervals 0.56-2.40. There was no linear dose-response. The lack of clear association for red wine intake was consistently observed when we stratified the analyses by CRC stage at diagnosis and cancer site (colon or rectum). Moderate red wine consumption was not associated with reduced risk of colorectal cancer in this population of middle-aged men.

  17. Assessing needs and assets for building a regional network infrastructure to reduce cancer related health disparities.

    Science.gov (United States)

    Wells, Kristen J; Lima, Diana S; Meade, Cathy D; Muñoz-Antonia, Teresita; Scarinci, Isabel; McGuire, Allison; Gwede, Clement K; Pledger, W Jack; Partridge, Edward; Lipscomb, Joseph; Matthews, Roland; Matta, Jaime; Flores, Idhaliz; Weiner, Roy; Turner, Timothy; Miele, Lucio; Wiese, Thomas E; Fouad, Mona; Moreno, Carlos S; Lacey, Michelle; Christie, Debra W; Price-Haywood, Eboni G; Quinn, Gwendolyn P; Coppola, Domenico; Sodeke, Stephen O; Green, B Lee; Lichtveld, Maureen Y

    2014-06-01

    Significant cancer health disparities exist in the United States and Puerto Rico. While numerous initiatives have been implemented to reduce cancer disparities, regional coordination of these efforts between institutions is often limited. To address cancer health disparities nation-wide, a series of regional transdisciplinary networks through the Geographic Management Program (GMaP) and the Minority Biospecimen/Biobanking Geographic Management Program (BMaP) were established in six regions across the country. This paper describes the development of the Region 3 GMaP/BMaP network composed of over 100 investigators from nine institutions in five Southeastern states and Puerto Rico to develop a state-of-the-art network for cancer health disparities research and training. We describe a series of partnership activities that led to the formation of the infrastructure for this network, recount the participatory processes utilized to develop and implement a needs and assets assessment and implementation plan, and describe our approach to data collection. Completion, by all nine institutions, of the needs and assets assessment resulted in several beneficial outcomes for Region 3 GMaP/BMaP. This network entails ongoing commitment from the institutions and institutional leaders, continuous participatory and engagement activities, and effective coordination and communication centered on team science goals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Reflections on multiple strategies to reduce transfusion in cancer patients: A joint narrative.

    Science.gov (United States)

    Goubran, Hadi; Seghatchian, Jerard; Prokopchuk-Gauk, Oksana; Radosevic, Julia; Sabry, Waleed; Iqbal, Nayyer; Burnouf, Thierry

    2017-06-01

    Transfusion of red blood cells, platelets and plasma is widely used in the management of anemia and coagulopathy in cancer patients undergoing surgery, chemotherapy, and radiation. The decision to transfuse should not be made lightly as exposure to transfused blood, whether from an allogeneic or even autologous source, is not without risk and the long-term effect of blood transfusion on cancer outcomes remains questionable. Recognition of anemia associated with nutritional deficiency should be promptly corrected while avoiding the use of erythropoiesis stimulating agents. Minimizing blood loss and the prompt control of bleeding, coupled with a restrictive transfusion strategy, seem to be a reasonable approach that does not appear to be associated with long-term sequelae. Limiting platelet transfusion to patients with severe hypo-proliferative thrombocytopenia, and implementation of local hemostatic measures, together with the use of fractionated coagulation factor concentrates, as an alternative to frozen plasma transfusion, may reduce the exposure of cancer patients to potentially harmful thrombogenic and pro-inflammatory cellular microparticles. This joint narrative highlights current opinions for minimizing blood usage in patients with cancer. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  19. Assessing Needs and Assets for Building a Regional Network Infrastructure to Reduce Cancer Related Health Disparities

    Science.gov (United States)

    Wells, Kristen J.; Lima, Diana S.; Meade, Cathy D.; Muñoz-Antonia, Teresita; Scarinci, Isabel; McGuire, Allison; Gwede, Clement K.; Pledger, W. Jack; Partridge, Edward; Lipscomb, Joseph; Matthews, Roland; Matta, Jaime; Flores, Idhaliz; Weiner, Roy; Turner, Timothy; Miele, Lucio; Wiese, Thomas E.; Fouad, Mona; Moreno, Carlos S.; Lacey, Michelle; Christie, Debra W.; Price-Haywood, Eboni G.; Quinn, Gwendolyn P.; Coppola, Domenico; Sodeke, Stephen O.; Green, B. Lee; Lichtveld, Maureen Y.

    2015-01-01

    Significant cancer health disparities exist in the United States and Puerto Rico. While numerous initiatives have been implemented to reduce cancer disparities, regional coordination of these efforts between institutions is often limited. To address cancer health disparities nationwide, a series of regional transdisciplinary networks through the Geographic Management Program (GMaP) and the Minority Biospecimen/Biobanking Geographic Management Program (BMaP) were established in six regions across the country. This paper describes the development of the Region 3 GMaP/BMaP network composed of over 100 investigators from nine institutions in five Southeastern states and Puerto Rico to develop a state-of-the-art network for cancer health disparities research and training. We describe a series of partnership activities that led to the formation of the infrastructure for this network, recount the participatory processes utilized to develop and implement a needs and assets assessment and implementation plan, and describe our approach to data collection. Completion, by all nine institutions, of the needs and assets assessment resulted in several beneficial outcomes for Region 3 GMaP/BMaP. This network entails ongoing commitment from the institutions and institutional leaders, continuous participatory and engagement activities, and effective coordination and communication centered on team science goals. PMID:24486917

  20. Transcriptomics of shading-induced and NAA-induced abscission in apple (Malus domestica) reveals a shared pathway involving reduced photosynthesis, alterations in carbohydrate transport and signaling and hormone crosstalk.

    Science.gov (United States)

    Zhu, Hong; Dardick, Chris D; Beers, Eric P; Callanhan, Ann M; Xia, Rui; Yuan, Rongcai

    2011-10-17

    Naphthaleneacetic acid (NAA), a synthetic auxin analogue, is widely used as an effective thinner in apple orchards. When applied shortly after fruit set, some fruit abscise leading to improved fruit size and quality. However, the thinning results of NAA are inconsistent and difficult to predict, sometimes leading to excess fruit drop or insufficient thinning which are costly to growers. This unpredictability reflects our incomplete understanding of the mode of action of NAA in promoting fruit abscission. Here we compared NAA-induced fruit drop with that caused by shading via gene expression profiling performed on the fruit abscission zone (FAZ), sampled 1, 3, and 5 d after treatment. More than 700 genes with significant changes in transcript abundance were identified from NAA-treated FAZ. Combining results from both treatments, we found that genes associated with photosynthesis, cell cycle and membrane/cellular trafficking were downregulated. On the other hand, there was up-regulation of genes related to ABA, ethylene biosynthesis and signaling, cell wall degradation and programmed cell death. While the differentially expressed gene sets for NAA and shading treatments shared only 25% identity, NAA and shading showed substantial similarity with respect to the classes of genes identified. Specifically, photosynthesis, carbon utilization, ABA and ethylene pathways were affected in both NAA- and shading-induced young fruit abscission. Moreover, we found that NAA, similar to shading, directly interfered with leaf photosynthesis by repressing photosystem II (PSII) efficiency within 10 minutes of treatment, suggesting that NAA and shading induced some of the same early responses due to reduced photosynthesis, which concurred with changes in hormone signaling pathways and triggered fruit abscission. This study provides an extensive transcriptome study and a good platform for further investigation of possible regulatory genes involved in the induction of young fruit

  1. Combined functional CT/FDG-PET: demonstrates reduced hepatic phosphorylation of glucose in advanced colorectal cancer

    International Nuclear Information System (INIS)

    Miles, K.A.; Keith, C.J.; Griffiths, M.R.; Fuentes, M.; Bunce, I.

    2002-01-01

    Full text: This study describes a technique to quantify hepatic glucose phosphorylation using combined data from functional CT and FDG-PET and assesses the differences in phosphorylation between patients with either early or advanced colorectal cancer. Functional CT and FDG-PET were utilised to obtain measurements of perfusion and glucose uptake respectively within the livers of a series of 35 patients with colorectal cancer. Patients with PET evidence of extrahepatic tumour were considered to have advanced disease. The net influx constant (Ki) for FDG was determined from the liver SUV. CT measurements of hepatic perfusion were incorporated into FDG kinetic analysis to determine hepatic glucose phosphorylation fraction. SUV and Ki were significantly lower in the 12 patients with advanced disease (p=0.015 and p=0.013 respectively) whereas portal and total hepatic perfusion were increased (p=0.013 and p=0.008 respectively). Combining the PET and CT data yielded phosphorylation fractions of 1.14% and 0.74% for early and advanced disease respectively (p=0.002). Hepatic glucose phosphorylation can be determined by combining functional CT measurements of perfusion with PET measurements of FDG and is significantly reduced in patients with more advanced malignancy. Reduced hepatic glucose phosphorylation may be an important mechanism in the development of cancer cachexia. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  2. Combined functional CT/FDG-PET: demonstrates reduced hepatic phosphorylation of glucose in advanced colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Miles, K A [Southernex Imaging Group, QLD (Australia); Queensland University of Technology, QLD (Australia); Keith, C J [Southernex Imaging Group, QLD (Australia); Wesley Research Institute, QLD (Australia); Griffiths, M R [Queensland University of Technology, QLD (Australia); Fuentes, M [Southernex Imaging Group, QLD (Australia); Bunce, I [Wesley Research Institute, QLD (Australia)

    2002-07-01

    Full text: This study describes a technique to quantify hepatic glucose phosphorylation using combined data from functional CT and FDG-PET and assesses the differences in phosphorylation between patients with either early or advanced colorectal cancer. Functional CT and FDG-PET were utilised to obtain measurements of perfusion and glucose uptake respectively within the livers of a series of 35 patients with colorectal cancer. Patients with PET evidence of extrahepatic tumour were considered to have advanced disease. The net influx constant (Ki) for FDG was determined from the liver SUV. CT measurements of hepatic perfusion were incorporated into FDG kinetic analysis to determine hepatic glucose phosphorylation fraction. SUV and Ki were significantly lower in the 12 patients with advanced disease (p=0.015 and p=0.013 respectively) whereas portal and total hepatic perfusion were increased (p=0.013 and p=0.008 respectively). Combining the PET and CT data yielded phosphorylation fractions of 1.14% and 0.74% for early and advanced disease respectively (p=0.002). Hepatic glucose phosphorylation can be determined by combining functional CT measurements of perfusion with PET measurements of FDG and is significantly reduced in patients with more advanced malignancy. Reduced hepatic glucose phosphorylation may be an important mechanism in the development of cancer cachexia. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc.

  3. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-01-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 ± 3mm (mean ± SD) and 10 ± 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 ± 13cGy with Hylaform vs. 106 ± 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

  4. Physiotherapy programme reduces fatigue in patients with advanced cancer receiving palliative care: randomized controlled trial.

    Science.gov (United States)

    Pyszora, Anna; Budzyński, Jacek; Wójcik, Agnieszka; Prokop, Anna; Krajnik, Małgorzata

    2017-09-01

    Cancer-related fatigue (CRF) is a common and relevant symptom in patients with advanced cancer that significantly decreases their quality of life. The aim of this study was to evaluate the effect of a physiotherapy programme on CRF and other symptoms in patients diagnosed with advanced cancer. The study was designed as a randomized controlled trial. Sixty patients diagnosed with advanced cancer receiving palliative care were randomized into two groups: the treatment group (n = 30) and the control group (n = 30). The therapy took place three times a week for 2 weeks. The 30-min physiotherapy session included active exercises, myofascial release and proprioceptive neuromuscular facilitation (PNF) techniques. The control group did not exercise. The outcomes included Brief Fatigue Inventory (BFI), Edmonton Symptom Assessment Scale (ESAS) and satisfaction scores. The exercise programme caused a significant reduction in fatigue scores (BFI) in terms of severity of fatigue and its impact on daily functioning. In the control group, no significant changes in the BFI were observed. Moreover, the physiotherapy programme improved patients' general well-being and reduced the intensity of coexisting symptoms such as pain, drowsiness, lack of appetite and depression. The analysis of satisfaction scores showed that it was also positively evaluated by patients. The physiotherapy programme, which included active exercises, myofascial release and PNF techniques, had beneficial effects on CRF and other symptoms in patients with advanced cancer who received palliative care. The results of the study suggest that physiotherapy is a safe and effective method of CRF management.

  5. Reduced risk of breast cancer associated with recreational physical activity varies by HER2 status

    International Nuclear Information System (INIS)

    Ma, Huiyan; Xu, Xinxin; Ursin, Giske; Simon, Michael S; Marchbanks, Polly A; Malone, Kathleen E; Lu, Yani; McDonald, Jill A; Folger, Suzanne G; Weiss, Linda K; Sullivan-Halley, Jane; Deapen, Dennis M; Press, Michael F; Bernstein, Leslie

    2015-01-01

    Convincing epidemiologic evidence indicates that physical activity is inversely associated with breast cancer risk. Whether this association varies by the tumor protein expression status of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), or p53 is unclear. We evaluated the effects of recreational physical activity on risk of invasive breast cancer classified by the four biomarkers, fitting multivariable unconditional logistic regression models to data from 1195 case and 2012 control participants in the population-based Women’s Contraceptive and Reproductive Experiences Study. Self-reported recreational physical activity at different life periods was measured as average annual metabolic equivalents of energy expenditure [MET]-hours per week. Our biomarker-specific analyses showed that lifetime recreational physical activity was negatively associated with the risks of ER-positive (ER+) and of HER2-negative (HER2−) subtypes (both P trend ≤ 0.04), but not with other subtypes (all P trend > 0.10). Analyses using combinations of biomarkers indicated that risk of invasive breast cancer varied only by HER2 status. Risk of HER2–breast cancer decreased with increasing number of MET-hours of recreational physical activity in each specific life period examined, although some trend tests were only marginally statistically significant (all P trend ≤ 0.06). The test for homogeneity of trends (HER2– vs. HER2+) reached statistical significance only when evaluating physical activity during the first 10 years after menarche (P homogeneity = 0.03). Our data suggest that physical activity reduces risk of invasive breast cancers that lack HER2 overexpression, increasing our understanding of the biological mechanisms by which physical activity acts

  6. Oestradiol reduces Liver Receptor Homolog-1 mRNA transcript stability in breast cancer cell lines

    International Nuclear Information System (INIS)

    Lazarus, Kyren A.; Zhao, Zhe; Knower, Kevin C.; To, Sarah Q.; Chand, Ashwini L.; Clyne, Colin D.

    2013-01-01

    Highlights: •LRH-1 is an orphan nuclear receptor that regulates tumor proliferation. •In breast cancer, high mRNA expression is associated with ER+ status. •In ER−ve cells, despite very low mRNA, we found abundant LRH-1 protein. •Our data show distinctly different LRH-1 protein isoforms in ER− and ER+ breast cancer cells. •This is due to differences in LRH-1 mRNA and protein stability rates. -- Abstract: The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E 2 ), with LRH-1 mRNA transcript levels higher in oestrogen receptor α (ERα) positive (ER+) breast cancer cells compared to ER− cells. However, the presence of LRH-1 protein in ER− cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER− breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER− compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E 2 , showed increased mRNA stability in ER− versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E 2 treatment, this effect mediated by ERα. Our data demonstrates that in ER− cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER− cells as well as ER− tumors suggests a possible role in the development of ER− tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER− and ER+ breast cancer

  7. Oestradiol reduces Liver Receptor Homolog-1 mRNA transcript stability in breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Lazarus, Kyren A. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Environmental and Biotechnology Centre, Swinburne University, Hawthorn, Victoria 3122 (Australia); Zhao, Zhe; Knower, Kevin C. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); To, Sarah Q. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168 (Australia); Chand, Ashwini L. [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Clyne, Colin D., E-mail: Colin.clyne@princehenrys.org [Cancer Drug Discovery Laboratory, Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168 (Australia); Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3168 (Australia)

    2013-08-30

    Highlights: •LRH-1 is an orphan nuclear receptor that regulates tumor proliferation. •In breast cancer, high mRNA expression is associated with ER+ status. •In ER−ve cells, despite very low mRNA, we found abundant LRH-1 protein. •Our data show distinctly different LRH-1 protein isoforms in ER− and ER+ breast cancer cells. •This is due to differences in LRH-1 mRNA and protein stability rates. -- Abstract: The expression of orphan nuclear receptor Liver Receptor Homolog-1 (LRH-1) is elevated in breast cancer and promotes proliferation, migration and invasion in vitro. LRH-1 expression is regulated by oestrogen (E{sub 2}), with LRH-1 mRNA transcript levels higher in oestrogen receptor α (ERα) positive (ER+) breast cancer cells compared to ER− cells. However, the presence of LRH-1 protein in ER− cells suggests discordance between mRNA transcript levels and protein expression. To understand this, we investigated the impact of mRNA and protein stability in determining LRH-1 protein levels in breast cancer cells. LRH-1 transcript levels were significantly higher in ER+ versus ER− breast cancer cells lines; however LRH-1 protein was expressed at similar levels. We found LRH-1 mRNA and protein was more stable in ER− compared to ER+ cell lines. The tumor-specific LRH-1 variant isoform, LRH-1v4, which is highly responsive to E{sub 2}, showed increased mRNA stability in ER− versus ER+ cells. In addition, in MCF-7 and T47-D cell lines, LRH-1 total mRNA stability was reduced with E{sub 2} treatment, this effect mediated by ERα. Our data demonstrates that in ER− cells, increased mRNA and protein stability contribute to the abundant protein expression levels. Expression and immunolocalisation of LRH-1 in ER− cells as well as ER− tumors suggests a possible role in the development of ER− tumors. The modulation of LRH-1 bioactivity may therefore be beneficial as a treatment option in both ER− and ER+ breast cancer.

  8. Apoptosis inducing ability of silver decorated highly reduced graphene oxide nanocomposites in A549 lung cancer

    Directory of Open Access Journals (Sweden)

    Khan M

    2016-03-01

    Full Text Available Merajuddin Khan,1 Mujeeb Khan,1 Abdulhadi H Al-Marri,1 Abdulrahman Al-Warthan,1 Hamad Z Alkhathlan,1 Mohammed Rafiq H Siddiqui,1 Vadithe Lakshma Nayak,2 Ahmed Kamal,2 Syed F Adil1 1Department of Chemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia; 2Department of Medicinal Chemistry and Pharmacology, CSIR – Indian Institute of Chemical Technology, Hyderabad, India Abstract: Recently, graphene and graphene-based materials have been increasingly used for various biological applications due to their extraordinary physicochemical properties. Here, we demonstrate the anticancer properties and apoptosis-inducing ability of silver doped highly reduced graphene oxide nanocomposites synthesized by employing green approach. These nano­composites (PGE-HRG-Ag were synthesized by using Pulicaria glutinosa extract (PGE as a reducing agent and were evaluated for their anticancer properties against various human cancer cell lines with tamoxifen as the reference drug. A correlation between the amount of Ag nanoparticles on the surface of highly reduced graphene oxide (HRG and the anticancer activity of nanocomposite was observed, wherein an increase in the concentration of Ag nanoparticles on the surface of HRG led to the enhanced anticancer activity of the nanocomposite. The nanocomposite PGE-HRG-Ag-2 exhibited more potent cytotoxicity than standard drug in A549 cells, a human lung cancer cell line. A detailed investigation was undertaken and Fluorescence activated cell sorting (FACS analysis demonstrated that the nanocomposite PGE-HRG-Ag-2 showed G0/G1 phase cell cycle arrest and induced apoptosis in A549 cells. Studies such as, measurement of mitochondrial membrane potential, generation of reactive oxygen species (ROS and Annexin V-FITC staining assay suggested that this compound induced apoptosis in human lung cancer cells. Keywords: plant extract, graphene/silver nanocomposites, anticancer, apoptosis

  9. Electroacupuncture reduces duration of postoperative ileus after laparoscopic surgery for colorectal cancer.

    Science.gov (United States)

    Ng, Simon S M; Leung, Wing Wa; Mak, Tony W C; Hon, Sophie S F; Li, Jimmy C M; Wong, Cherry Y N; Tsoi, Kelvin K F; Lee, Janet F Y

    2013-02-01

    We investigated the efficacy of electroacupuncture in reducing the duration of postoperative ileus and hospital stay after laparoscopic surgery for colorectal cancer. We performed a prospective study of 165 patients undergoing elective laparoscopic surgery for colonic and upper rectal cancer, enrolled from October 2008 to October 2010. Patients were assigned randomly to groups that received electroacupuncture (n = 55) or sham acupuncture (n = 55), once daily from postoperative days 1-4, or no acupuncture (n = 55). The acupoints Zusanli, Sanyinjiao, Hegu, and Zhigou were used. The primary outcome was time to defecation. Secondary outcomes included postoperative analgesic requirement, time to ambulation, and length of hospital stay. Patients who received electroacupuncture had a shorter time to defecation than patients who received no acupuncture (85.9 ± 36.1 vs 122.1 ± 53.5 h; P electroacupuncture also had a shorter time to defecation than patients who received sham acupuncture (85.9 ± 36.1 vs 107.5 ± 46.2 h; P = .007). Electroacupuncture was more effective than no or sham acupuncture in reducing postoperative analgesic requirement and time to ambulation. In multiple linear regression analysis, an absence of complications and electroacupuncture were associated with a shorter duration of postoperative ileus and hospital stay after the surgery. In a clinical trial, electroacupuncture reduced the duration of postoperative ileus, time to ambulation, and postoperative analgesic requirement, compared with no or sham acupuncture, after laparoscopic surgery for colorectal cancer. ClinicalTrials.gov number, NCT00464425. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  10. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    David Qualtrough

    2015-09-01

    Full Text Available Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, Cancers 2015, 7 1886 these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  11. Nicaraven reduces cancer metastasis to irradiated lungs by decreasing CCL8 and macrophage recruitment.

    Science.gov (United States)

    Yan, Chen; Luo, Lan; Urata, Yoshishige; Goto, Shinji; Li, Tao-Sheng

    2018-04-01

    Radiotherapy for cancer patients damages normal tissues, thereby inducing an inflammatory response and promoting cancer metastasis. We investigated whether nicaraven, a compound with radioprotective and anti-inflammatory properties, could attenuate radiation-induced cancer metastasis to the lungs of mice. Nicaraven and amifostine, another commercial radioprotective agent, had limited effects on both the radiosensitivity of Lewis lung carcinoma cells in vitro and radiation-induced tumor growth inhibition in vivo. Using experimental and spontaneous metastasis models, we confirmed that thorax irradiation with 5 Gy X-rays dramatically increased the number of tumors in the lungs. Interestingly, the number of tumors in the lungs was significantly reduced by administering nicaraven but not by administering amifostine daily after radiation exposure. Furthermore, nicaraven administration effectively inhibited CCL8 expression and macrophage recruitment in the lungs 1 day after thorax irradiation. Our data suggest that nicaraven attenuates radiation-induced lung metastasis, likely by regulating the inflammatory response after radiation exposure. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. In vitro toxic effects of reduced graphene oxide nanosheets on lung cancer cells

    Science.gov (United States)

    Tabish, Tanveer A.; Pranjol, Md Zahidul I.; Hayat, Hasan; Rahat, Alma A. M.; Abdullah, Trefa M.; Whatmore, Jacqueline L.; Zhang, Shaowei

    2017-12-01

    The intriguing properties of reduced graphene oxide (rGO) have paved the way for a number of potential biomedical applications such as drug delivery, tissue engineering, gene delivery and bio-sensing. Over the last decade, there have been escalating concerns regarding the possible toxic effects, behaviour and fate of rGO in living systems and environments. This paper reports on integrative chemical-biological interactions of rGO with lung cancer cells, i.e. A549 and SKMES-1, to determine its potential toxicological impacts on them, as a function of its concentration. Cell viability, early and late apoptosis and necrosis were measured to determine oxidative stress potential, and induction of apoptosis for the first time by comparing two lung cancer cells. We also showed the general trend between cell death rates and concentrations for different cell types using a Gaussian process regression model. At low concentrations, rGO was shown to significantly produce late apoptosis and necrosis rather than early apoptotic events, suggesting that it was able to disintegrate the cellular membranes in a dose dependent manner. For the toxicity exposures undertaken, late apoptosis and necrosis occurred, which was most likely resultant from limited bioavailability of unmodified rGO in lung cancer cells.

  13. Laparoscopic stomach-partitioning gastrojejunostomy with reduced-port techniques for unresectable distal gastric cancer.

    Science.gov (United States)

    Hirahara, Noriyuki; Matsubara, Takeshi; Hyakudomi, Ryoji; Hari, Yoko; Fujii, Yusuke; Tajima, Yoshitsugu

    2014-03-01

    The improvement of quality of life is of great importance in managing patients with far-advanced gastric cancer. We report a new cure and less invasive method of creating a stomach-partitioning gastrojejunostomy in reduced-port laparoscopic surgery for unresectable gastric cancers with gastric outlet obstruction. A 2.5-cm vertical intraumbilical incision was made, and EZ Access (Hakko Co., Ltd., Tokyo, Japan) was placed. After pneumoperitoneum was created, an additional 5-mm trocar was inserted in the right upper abdomen. A gastrojejunostomy was performed in the form of an antiperistaltic side-to-side anastomosis, in which the jejunal loop was elevated in the antecolic route and anastomosed to the greater curvature of the stomach using an endoscopic linear stapler. The jejunal loop together with the stomach was dissected with additional linear staplers just proximal to the common entry hole so that a functional end-to-end gastrojejunostomy was completed. At the same time, the stomach was partitioned using a linear stapler to leave a 2-cm-wide lumen in the lesser curvature. Subsequently, jejunojejunostomy was performed 30 cm distal to the gastrojejunostomy, and the stomach-partitioning gastrojejunostomy resembling Roux-en Y anastomosis was completed. All patients resumed oral intake on the day of operation. Neither anastomotic leakage nor anastomotic stricture was observed. Our less invasive palliative operation offers the utmost priority to improve quality of life for patients with unresectable gastric cancer.

  14. Spiritual Well-being May Reduce the Negative Impacts of Cancer Symptoms on the Quality of Life and the Desire for Hastened Death in Terminally Ill Cancer Patients.

    Science.gov (United States)

    Wang, Yin-Chih; Lin, Chia-Chin

    2016-01-01

    Spirituality is a central component of the well-being of terminally ill cancer patients. The aim of this study was to examine the mediating or moderating role of spiritual well-being in reducing the impact of cancer-related symptoms on quality of life and the desire for hastened death in terminally ill cancer patients. Eighty-five terminally ill cancer patients were assessed using the Taiwanese version of the M. D. Anderson Symptom Inventory, the Functional Assessment of Cancer Therapy-General, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-being, the Beck Hopelessness Scale, and the Schedule of Attitudes Toward Hastened Death. Spiritual well-being was significantly negatively correlated with symptom severity (r = -0.46, P quality of life (r = -0.54) and positively correlated with hopelessness (r = 0.51, P quality of life. Spiritual well-being was a partial mediator between symptom severity and the desire for hastened death. The meaning subscale of spiritual well-being was a more significant predictor of the desire for hastened death and quality of life than the faith subscale was. Spiritual well-being may reduce the negative impacts of cancer on quality of life and the desire for hastened death. Appropriate spiritual care may reduce the negative impact of severe cancer symptoms on quality of life and the desire for hastened death in terminally ill cancer patients.

  15. Docetaxel-loaded solid lipid nanoparticles suppress breast cancer cells growth with reduced myelosuppression toxicity

    Directory of Open Access Journals (Sweden)

    Yuan Q

    2014-10-01

    Full Text Available Qing Yuan,1 Jing Han,1,2 Wenshu Cong,1 Ying Ge,3 Dandan Ma,1,3,4 Zhaoxia Dai,3,4 Yaping Li,5 Xiaolin Bi1,3,4 1CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 2School of Life Sciences, Anhui University, Hefei, 3Cancer Center, Institute of Cancer Stem Cell, Dalian Medical University, Dalian, 4Graduate School, Dalian Medical University, Dalian, 5Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: Docetaxel is an adjuvant chemotherapy drug widely used to treat multiple solid tumors; however, its toxicity and side effects limit its clinical efficacy. Herein, docetaxel-loaded solid lipid nanoparticles (DSNs were developed to reduce systemic toxicity of docetaxel while still keeping its anticancer activity. To evaluate its anticancer activity and toxicity, and to understand the molecular mechanisms of DSNs, different cellular, molecular, and whole genome transcription analysis approaches were utilized. The DSNs showed lower cytotoxicity compared with the commercial formulation of docetaxel (Taxotere® and induced more apoptosis at 24 hours after treatment in vitro. DSNs can cause the treated cancer cells to arrest in the G2/M phase in a dose-dependent manner similar to Taxotere. They can also suppress tumor growth very effectively in a mice model with human xenograft breast cancer. Systemic analysis of gene expression profiles by microarray and subsequent verification experiments suggested that both DSNs and Taxotere regulate gene expression and gene function, including DNA replication, DNA damage response, cell proliferation, apoptosis, and cell cycle regulation. Some of these genes expressed differentially at the protein level although their messenger RNA expression level was similar under Taxotere and DSN treatment. Moreover, DSNs improved the main side effect of Taxotere by greatly

  16. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Samuelian, Jason M. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Callister, Matthew D., E-mail: Callister.matthew@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Ashman, Jonathan B. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States); Young-Fadok, Tonia M. [Division of Colorectal Surgery, Mayo Clinic, Scottsdale, AZ (United States); Borad, Mitesh J. [Division of Hematology-Oncology, Mayo Clinic, Scottsdale, AZ (United States); Gunderson, Leonard L. [Department of Radiation Oncology, Mayo Clinic, Scottsdale, AZ (United States)

    2012-04-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced {>=}Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, {>=}Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  17. Assessing the Risk of Occult Cancer and 30-day Morbidity in Women Undergoing Risk-reducing Surgery: A Prospective Experience.

    Science.gov (United States)

    Bogani, Giorgio; Tagliabue, Elena; Signorelli, Mauro; Chiappa, Valentina; Carcangiu, Maria Luisa; Paolini, Biagio; Casarin, Jvan; Scaffa, Cono; Gennaro, Massimiliano; Martinelli, Fabio; Borghi, Chiara; Ditto, Antonino; Lorusso, Domenica; Raspagliesi, Francesco

    To investigate the incidence and predictive factors of 30-day surgery-related morbidity and occult precancerous and cancerous conditions for women undergoing risk-reducing surgery. A prospective study (Canadian Task Force classification II-1). A gynecologic oncology referral center. Breast-related cancer antigen (BRCA) mutation carriers and BRCAX patients (those with a significant family history of breast and ovarian cancer). Minimally invasive risk-reduction surgery. Overall, 85 women underwent risk-reducing surgery: 30 (35%) and 55 (65%) had hysterectomy plus bilateral salpingo-oophorectomy (BSO) and BSO alone, respectively. Overall, in 6 (7%) patients, the final pathology revealed unexpected cancer: 3 early-stage ovarian/fallopian tube cancers, 2 advanced-stage ovarian cancers (stage IIIA and IIIB), and 1 serous endometrial carcinoma. Additionally, 3 (3.6%) patients had incidental finding of serous tubal intraepithelial carcinoma. Four (4.7%) postoperative complications within 30 days from surgery were registered, including fever (n = 3) and postoperative ileus (n = 1); no severe (grade 3 or more) complications were observed. All complications were managed conservatively. The presence of occult cancer was the only factor predicting the development of postoperative complications (p = .02). Minimally invasive risk-reducing surgery is a safe and effective strategy to manage BRCA mutation carriers. Patients should benefit from an appropriate counseling about the high prevalence of undiagnosed cancers observed at the time of surgery. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

  18. Water enema CT examination of rectum cancer by reduced amount of water

    International Nuclear Information System (INIS)

    Palko, A.; Gyulai, Cs.; Fedinecz, N.; Balogh, A.; Nagy, F.

    2000-01-01

    To define whether volume of water, administered during water enema CT (WE-CT) for local staging of rectal cancer, may be reduced without compromising the diagnostic value of the examination. Materials and Methods: 29 patients with rectum cancer underwent preoperative WE-CT. Contrast-enhanced CT (equilibrium phase) measurements were performed after i.v. injection of smooth muscle relaxant and rectal administration of 400 - 500 ml lukewarm tap water. Quality of the obtained scans was evaluated and the images were analyzed for depth of tumor invasion. Results of the CT examinations were compared to findings at surgery. Results: Despite reduced dose of water enema, 19/29 examinations were of excellent quality, 6/29 good, and 4/29 poor, but still diagnostic. We achieved sensitivity (90.1), specificity (70.1) and accuracy (86.2) in differentiating tumors confined to the bowel wall from those extending beyond it. Conclusion: Large volume of water enema administered during CT examination of the rectum may cause complaints and increases the risk of complications. Our results prove that using lower amount of water does not impair the quality of examination and accuracy of local staging of rectum carcinomas. (orig.) [de

  19. Finasteride Reduces Risk of Bladder Cancer in a Large Prospective Screening Study.

    Science.gov (United States)

    Morales, Edwin E; Grill, Sonja; Svatek, Robert S; Kaushik, Dharam; Thompson, Ian M; Ankerst, Donna P; Liss, Michael A

    2016-03-01

    The androgen receptor has been implicated in the development and progression of bladder cancer (BCa), largely based on studies of animal models. We investigated whether finasteride was associated with a reduced incidence of BCa as observed by self-report in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial. Cox proportional hazard regression analysis was performed to determine the association of finasteride use with time to diagnosis of BCa, controlling for age and tobacco use. Of the 72,370 male participants who met inclusion criteria, 6069 (8.4%) had reported the use of finasteride. BCa was diagnosed in 1.07% (65 of 6069) of those who reported finasteride compared with 1.46% (966 of 66,301) of those who reported no use during the trial. In a multiple Cox regression analysis, self-reported use of finasteride was associated with a decreased risk of development of BCa (hazard ratio: 0.634; 95% confidence interval, 0.493-0.816; p=0.0004), controlling for age and smoking. Limitations of this study include that it is observational and not randomized, that many of the confounding variables for BCa, such as alcohol use, were not available for use in the analysis, and that finasteride use was by annual self-report, which is subject to missing values and error. Finasteride is a common medication used to reduce the size of the prostate and to promote hair growth by manipulating testosterone in men. Men are more likely than women to develop bladder cancer (BCa), but our study noted that men using finasteride were less likely to have a BCa diagnosis. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  20. Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Hummon Amanda B

    2012-01-01

    Full Text Available Abstract Background Colorectal carcinomas (CRC carry massive genetic and transcriptional alterations that influence multiple cellular pathways. The study of proteins whose loss-of-function (LOF alters the growth of CRC cells can be used to further understand the cellular processes cancer cells depend upon for survival. Results A small-scale RNAi screen of ~400 genes conducted in SW480 CRC cells identified several candidate genes as required for the viability of CRC cells, most prominently CASP8AP2/FLASH. To understand the function of this gene in maintaining the viability of CRC cells in an unbiased manner, we generated gene specific expression profiles following RNAi. Silencing of CASP8AP2/FLASH resulted in altered expression of over 2500 genes enriched for genes associated with cellular growth and proliferation. Loss of CASP8AP2/FLASH function was significantly associated with altered transcription of the genes encoding the replication-dependent histone proteins as a result of the expression of the non-canonical polyA variants of these transcripts. Silencing of CASP8AP2/FLASH also mediated enrichment of changes in the expression of targets of the NFκB and MYC transcription factors. These findings were confirmed by whole transcriptome analysis of CASP8AP2/FLASH silenced cells at multiple time points. Finally, we identified and validated that CASP8AP2/FLASH LOF increases the expression of neurofilament heavy polypeptide (NEFH, a protein recently linked to regulation of the AKT1/ß-catenin pathway. Conclusions We have used unbiased RNAi based approaches to identify and characterize the function of CASP8AP2/FLASH, a protein not previously reported as required for cell survival. This study further defines the role CASP8AP2/FLASH plays in the regulating expression of the replication-dependent histones and shows that its LOF results in broad and reproducible effects on the transcriptome of colorectal cancer cells including the induction of

  1. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Qualtrough, David, E-mail: david.qualtrough@uwe.ac.uk [Department of Biological, Biomedical & Analytical Sciences, University of the West of England, Faculty of Health and Applied Sciences, University of the West of England, Frenchay, Bristol BS16 1QY (United Kingdom); Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos [School of Cellular & Molecular Medicine, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD (United Kingdom)

    2015-09-17

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  2. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    International Nuclear Information System (INIS)

    Qualtrough, David; Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos

    2015-01-01

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer

  3. A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Archibald M

    2016-01-01

    Full Text Available Monica Archibald,1 Tara Pritchard,1 Hayley Nehoff,1 Rhonda J Rosengren,1 Khaled Greish,1,2 Sebastien Taurin1 1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand; 2Aljawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Kingdom of Bahrain Abstract: Castrate-resistant prostate cancer (CRPC remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs, sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene-co-maleic acid micelles. The micelles’ charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing. Keywords: sorafenib, nilotinib, castrate-resistant prostate cancer, tyrosine kinase inhibitors, nanomedicine

  4. TCW: transcriptome computational workbench.

    Science.gov (United States)

    Soderlund, Carol; Nelson, William; Willer, Mark; Gang, David R

    2013-01-01

    The analysis of transcriptome data involves many steps and various programs, along with organization of large amounts of data and results. Without a methodical approach for storage, analysis and query, the resulting ad hoc analysis can lead to human error, loss of data and results, inefficient use of time, and lack of verifiability, repeatability, and extensibility. The Transcriptome Computational Workbench (TCW) provides Java graphical interfaces for methodical analysis for both single and comparative transcriptome data without the use of a reference genome (e.g. for non-model organisms). The singleTCW interface steps the user through importing transcript sequences (e.g. Illumina) or assembling long sequences (e.g. Sanger, 454, transcripts), annotating the sequences, and performing differential expression analysis using published statistical programs in R. The data, metadata, and results are stored in a MySQL database. The multiTCW interface builds a comparison database by importing sequence and annotation from one or more single TCW databases, executes the ESTscan program to translate the sequences into proteins, and then incorporates one or more clusterings, where the clustering options are to execute the orthoMCL program, compute transitive closure, or import clusters. Both singleTCW and multiTCW allow extensive query and display of the results, where singleTCW displays the alignment of annotation hits to transcript sequences, and multiTCW displays multiple transcript alignments with MUSCLE or pairwise alignments. The query programs can be executed on the desktop for fastest analysis, or from the web for sharing the results. It is now affordable to buy a multi-processor machine, and easy to install Java and MySQL. By simply downloading the TCW, the user can interactively analyze, query and view their data. The TCW allows in-depth data mining of the results, which can lead to a better understanding of the transcriptome. TCW is freely available from www.agcol.arizona.edu/software/tcw.

  5. Yoga-Based Rehabilitation Program in Reducing Physical and Emotional Side Effects in Patients With Cancer

    Science.gov (United States)

    2017-01-23

    Alopecia; Anxiety; Breast Carcinoma; Cognitive Side Effects of Cancer Therapy; Colorectal Carcinoma; Depression; Fatigue; Lung Carcinoma; Nausea and Vomiting; Pain; Psychological Impact of Cancer; Sleep Disorder; Weight Change

  6. Thoracic epidural analgesia reduces myocardial injury in ischemic patients undergoing major abdominal cancer surgery

    Directory of Open Access Journals (Sweden)

    Mohamad MF

    2017-04-01

    to PCIA at all measured time points. Regarding perioperative hemodynamics, there was a significant reduction in intra-operative mean arterial pressure (MAP; and heart rate in PCEA group in comparison to PCIA group at most of measured time points while there was not a significant reduction in postoperative MAP and heart rate in the second and third post-operative days. The incidence of other postoperative complications such as DVT, pneumonia and in hospital mortality were decreased in PCEA group.Conclusion: Perioperative thoracic epidural analgesia in patients suffering from coronary artery disease subjected to major abdominal cancer surgery reduced significantly postoperative major adverse cardiac events with better pain control in comparison with perioperative IV analgesia. Keywords: postoperative myocardial infarction, thoracic epidural analgesia, PCA

  7. A nonaxial boost may reduce late complications of radiotherapy for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ben-Josef, E; Mesina, C F; Choi, J; Forman, J D

    1995-07-01

    Purpose: The nonaxial external beam (NAEBT) prostate boost technique was designed to reduce late complications of radiotherapy for prostate cancer. It has been previously shown that with this beam arrangement, the volumes of bladder and rectum receiving high doses could be substantially reduced. This study was undertaken to find if these advantages in dose distribution would translate into clinically significant benefits. Materials and Methods: Follow-up was obtained on 106 prostate cancer patients who had been treated with 3D conformal radiotherapy. Late complications were scored using the RTOG scale. A standard four-field axial (STD) technique had been used to deliver 45 Gy to the prostate, seminal vesicles and periprostatic lymph-nodes. A subsequent 24 Gy boost had been delivered using a STD technique (58 patients) or a NAEBT technique (48 patients). In the latter, the opposing anterior and posterior pair of beams had been substituted for a right and left anterior infero-superior pair. Actuarial probabilities of developing late complications were calculated by the life-table method. The Mantel-Haenszel test was used to compare these probabilities between the two groups. Results: The groups were comparable in regard to age, race, pretreatment serum PSA, stage distribution and dose to prostate. With a median follow-up of 21 months, 18 patients have developed grade 1-2 gastrointestinal or genitourinary complications (14 in the STD group, 4 in the NAEBT group). There were no grade 3-4 complications. The actuarial 3-year complication probability was 58% and 11% in the STD and NAEBT groups, respectively. However, this difference was not statistically significant. Gastrointestinal and genitourinary complications were reduced from 12.1% to 6.2% and from 15.5% to 4.2%, respectively. Conclusion: The use of a nonaxial boost technique has resulted in fewer complications in patients treated with 3D conformal radiotherapy for localized prostate cancer. The greater reduction

  8. Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival

    International Nuclear Information System (INIS)

    Eftang, Lars L; Esbensen, Ying; Tannæs, Tone M; Blom, Gustav P; Bukholm, Ida RK; Bukholm, Geir

    2013-01-01

    The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastric adenocarcinomas from a Norwegian selection, compared to matched normal mucosa, and we have related our findings to prognosis, survival and chronic Helicobacter pylori infection. Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 20 patients immediately following surgical resection of the tumor. Whole genome, cDNA microarray analysis was performed on the RNA isolated from the sample pairs to compare the gene expression profiles between the tumor against matched mucosa. The samples were microscopically examined to classify gastritis. The presence of H. pylori was examined using microscopy and immunohistochemistry. 130 genes showed differential regulation above a predefined cut-off level. Interleukin-8 (IL-8) and Claudin-1 (CLDN1) were the most consistently up-regulated genes in the tumors. Very high CLDN1 expression in the tumor was identified as an independent and significant predictor gene of reduced post-operative survival. There were distinctly different expression profiles between the tumor group and the control mucosa group, and the histological subsets of mixed type, diffuse type and intestinal type cancer demonstrated further sub-clustering. Up-regulated genes were mapped to cell-adhesion, collagen-related processes and angiogenesis, whereas normal intestinal functions such as digestion and excretion were associated with down-regulated genes. We relate the current findings to our previous study on the gene response of gastric epithelial cells to H. pylori infection. CLDN1 was highly up-regulated in gastric cancer, and CLDN1 expression was independently associated with a poor post-operative prognosis, and may have important prognostic

  9. Are we able to reduce the mortality and morbidity of oral cancer; Some considerations

    NARCIS (Netherlands)

    van der Waal, I.

    2013-01-01

    Oral cancer makes up 1%-2% of all cancers that may arise in the body. The majority of oral cancers consists of squamous cell carcinomas. Oral cancer carries a considerable mortality rate, being mainly dependent on the stage of the disease at admission. Worldwide some 50% of the patients with oral

  10. Interventions to prevent skin cancer by reducing exposure to ultraviolet radiation: a systematic review.

    Science.gov (United States)

    Saraiya, Mona; Glanz, Karen; Briss, Peter A; Nichols, Phyllis; White, Cornelia; Das, Debjani; Smith, S Jay; Tannor, Bernice; Hutchinson, Angela B; Wilson, Katherine M; Gandhi, Nisha; Lee, Nancy C; Rimer, Barbara; Coates, Ralph C; Kerner, Jon F; Hiatt, Robert A; Buffler, Patricia; Rochester, Phyllis

    2004-12-01

    The relationship between skin cancer and ultraviolet radiation is well established. Behaviors such as seeking shade, avoiding sun exposure during peak hours of radiation, wearing protective clothing, or some combination of these behaviors can provide protection. Sunscreen use alone is not considered an adequate protection against ultraviolet radiation. This report presents the results of systematic reviews of effectiveness, applicability, other harms or benefits, economic evaluations, and barriers to use of selected interventions to prevent skin cancer by reducing exposure to ultraviolet radiation. The Task Force on Community Preventive Services found that education and policy approaches to increasing sun-protective behaviors were effective when implemented in primary schools and in recreational or tourism settings, but found insufficient evidence to determine effectiveness when implemented in other settings, such as child care centers, secondary schools and colleges, and occupational settings. They also found insufficient evidence to determine the effectiveness of interventions oriented to healthcare settings and providers, media campaigns alone, interventions oriented to parents or caregivers of children, and community-wide multicomponent interventions. The report also provides suggestions for areas for future research.

  11. Bolus effect to reduce skin dose of the caontralateral breast during breast cancer radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Won, Young Jin [Dept. of Radiation Oncology, InJe University Ilsan Paik Hospital, Goyang (Korea, Republic of); Kim, Jong Won; Kim, Jung Hoon [Dept. of Radiology, Radiation Oncology, KonYang University Hospital, Daejeon (Korea, Republic of)

    2017-06-15

    The aim of this study was to evaluate the dose comparison using Radon phantom with 5 mm and 10 mm tissue equivalent materials, FIF, Wedge(15, 30 angle) and IMRT, to reduce the skin dose of the contralateral breast during breast cancer radiation therapy(Total dose: 50.4Gy). The dose was measured for each treatment plan by attaching to the 8 point of the contralateral breast of the treated region using a optical-stimulated luminance dosimeter(OSLD) as a comparative dose evaluation method. Of the OSLD used in the study, 10 were used with reproducibility within 3%. As a result, the average reduction rates of 5 mm and 10 mm in the FIF treatment plan were 37.23 cGy and 41.77 cGy, respectively, and the average reduction rates in the treatment plan using Wedge 15 degrees were 70.69 cGy and 87.57 cGy, respectively. The IMRT showed a reduction of 67.37 cGy and 83.17 cGy, respectively. The results of using bolus showed that as the thickness of the bolus increased in all treatments, the dose reduction increased. We concluded that mastectomy as well as general radiotherapy for breast cancer would be very effective for patients who are more likely to be exposed to scattered radiation due to a more demanding or complex treatment plan.

  12. Evaluating proton stereotactic body radiotherapy to reduce chest wall dose in the treatment of lung cancer

    International Nuclear Information System (INIS)

    Welsh, James; Amini, Arya; Ciura, Katherine; Nguyen, Ngoc; Palmer, Matt; Soh, Hendrick; Allen, Pamela K.; Paolini, Michael; Liao, Zhongxing; Bluett, Jaques; Mohan, Radhe; Gomez, Daniel; Cox, James D.; Komaki, Ritsuko; Chang, Joe Y.

    2013-01-01

    Stereotactic body radiotherapy (SBRT) can produce excellent local control of several types of solid tumor; however, toxicity to nearby critical structures is a concern. We found previously that in SBRT for lung cancer, the chest wall (CW) volume receiving 20, 30, or 40 Gy (V 20 , V 30 , or V 40 ) was linked with the development of neuropathy. Here we sought to determine whether the dosimetric advantages of protons could produce lower CW doses than traditional photon-based SBRT. We searched an institutional database to identify patients treated with photon SBRT for lung cancer with tumors within 20 was 364.0 cm 3 and 160.0 cm 3 (p 30 was 144.6 cm 3 vs 77.0 cm 3 (p = 0.0012), V 35 was 93.9 cm 3 vs 57.9 cm 3 (p = 0.005), V 40 was 66.5 cm 3 vs 45.4 cm 3 (p = 0.0112), and mean lung dose was 5.9 Gy vs 3.8 Gy (p = 0.0001) for photons and protons, respectively. Coverage of the planning target volume (PTV) was comparable between the 2 sets of plans (96.4% for photons and 97% for protons). From a dosimetric standpoint, proton SBRT can achieve the same coverage of the PTV while significantly reducing the dose to the CW and lung relative to photon SBRT and therefore may be beneficial for the treatment of lesions closer to critical structures

  13. Effectiveness of tranexamic acid in reducing blood loss during cytoreductive surgery for advanced ovarian cancer.

    Science.gov (United States)

    Kietpeerakool, Chumnan; Supoken, Amornrat; Laopaiboon, Malinee; Lumbiganon, Pisake

    2016-01-23

    Ovarian cancer is the third most common gynaecological cancer worldwide, with an age-standardised incidence rate of 6.1 per 10,000 women. Standard therapy for advanced epithelial ovarian cancer (EOC) includes a combination of cytoreductive surgery and platinum-based chemotherapy. Cytoreductive surgery aims to remove as much of the visible tumour as possible. As extensive intraperitoneal metastases are typical of advanced EOC, cytoreductive surgery is usually an extensive procedure with the risk of excessive bleeding. Tranexamic acid given perioperatively is effective in reducing blood loss and allogeneic blood transfusion requirements in a variety of surgical settings. Therefore, tranexamic acid seems to be a promising agent for minimising blood loss and the need for blood transfusion among women with advanced EOC undergoing cytoreductive surgery. To assess the effects of tranexamic acid for reducing blood loss associated with cytoreductive surgery in women with advanced EOC (stage III to IV). We searched the Cochrane Gynaecological, Neuro-oncology and Orphan Cancers Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2015), MEDLINE, EMBASE and conference proceedings to May 2015. We also checked registers of clinical trials, citation lists of included studies, key textbooks and previous systematic reviews for potentially relevant studies. We included randomised controlled trials (RCTs) comparing tranexamic acid given during surgery versus placebo or no treatment, in adult women diagnosed with advanced EOC. Two review authors (CK, AS) independently selected potentially relevant trials, extracted data, assessed risk of bias, compared results and resolved disagreements by discussion. We found only one study that met our inclusion criteria. This was a randomised double blind, placebo-controlled multicentre study conducted to evaluate the effectiveness of a single dose of intravenous tranexamic acid (15 mg/kg body weight) versus

  14. Cytotoxic Induction and Photoacoustic Imaging of Breast Cancer Cells Using Astaxanthin-Reduced Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Subramaniyan Bharathiraja

    2016-04-01

    Full Text Available Astaxanthin, a kind of photosynthetic pigment, was employed for gold nanoparticle formation. Nanoparticles were characterized using Ulteraviolet-Visible (UV-Vis spectroscopy, transmission electron microscopy, and X-ray diffraction, and the possible presence of astaxanthin functional groups were analyzed by Fourier transform infrared spectroscopy (FTIR. The cytotoxic effect of synthesized nanoparticles was evaluated against MDA-MB-231 (human breast cancer cells using a tetrazolium-based assay, and synthesized nanoparticles exhibited dose-dependent toxicity. The morphology upon cell death was differentiated through fluorescent microscopy using different stains that predicted apoptosis. The synthesized nanoparticles were applied in ultrasound-coupled photoacoustic imaging to obtain good images of treated cells. Astaxanthin-reduced gold nanoparticle has the potential to act as a promising agent in the field of photo-based diagnosis and therapy.

  15. Reduced hypothalamic blood flow after radiation treatment of nasopharyngeal cancer: SPECT studies in 34 patients

    International Nuclear Information System (INIS)

    Chieng, P.U.; Huang, T.S.; Chang, C.C.; Chong, P.N.; Tien, R.D.; Su, C.T.

    1991-01-01

    To determine the effect of cranial irradiation on hypothalamic blood flow, the authors performed 44 regional cerebral blood flow studies with 99mTc hexamethyl propyleneamine oxime (HMPAO) single-photon emission CT (SPECT) on four normal volunteers and 34 patients with pathologically proved nasopharyngeal cancer. Twenty-three men and 15 women, 30-65 years old, were divided into four study groups: group 1 served as a control and consisted of four normal volunteers and six patients studied prior to cranial irradiation; group 2 patients had cranial irradiation half a year before the SPECT study (n = 12, one from group 1); group 3 patients were irradiated 1 year before the study (n = 13, three from group 1 and two from group 2); and group 4 patients were irradiated at least 5 years before SPECT imaging (n = 9). Six patients were studied twice. Quantification of the 99mTc-HMPAO brain SPECT studies was done separately by three radiologists to obtain the hypothalamus/occipital (H/O) and hypothalamus/parasagittal (H/P) ratios. Endocrinologic studies were performed in all cases and the hypothalamus-thyrotroph-thyroid, hypothalamus-gonadotroph-testis (ovary), hypothalamus-lactotroph, hypothalamus-somatotroph, and hypothalamus-corticotroph-adrenal axes were evaluated separately. They determined that regional hypothalamic blood flow was reduced after cranial irradiation in patients with nasopharyngeal cancer. The H/O ratio of groups 3 and 4 did not differ from that of group 2 (one-half year after cranial irradiation). The H/O ratio was significantly reduced 6 months and 1 year after cranial irradiation; mean ± SD = 0.5801 ± 0.0829 (p less than .025), 0.5725 ± 0.0791 (p less than .01) versus 0.6477 ± 0.0458 before cranial irradiation, respectively

  16. The costs of reducing loss to follow-up in South African cervical cancer screening

    Directory of Open Access Journals (Sweden)

    Kuhn Louise

    2005-11-01

    Full Text Available Abstract Background This study was designed to quantify the resources used in reestablishing contact with women who missed their scheduled cervical cancer screening visits and to assess the success of this effort in reducing loss to follow-up in a developing country setting. Methods Women were enrolled in this Cape Town, South Africa-based screening study between 2000 and 2003, and all had scheduled follow-up visits in 2003. Community health worker (CHW time, vehicle use, maintenance, and depreciation were estimated from weekly logs and cost accounting systems. The percentage of women who attended their scheduled visit, those who attended after CHW contact(s, and those who never returned despite attempted contact(s were determined. The number of CHW visits per woman was also estimated. Results 3,711 visits were scheduled in 2003. Of these, 2,321 (62.5% occurred without CHW contact, 918 (24.8% occurred after contact(s, and 472 (12.7% did not occur despite contact(s. Loss to follow-up was reduced from 21% to 6%, 39% to 10%, and 50% to 24% for 6, 12, and 24-month visits. CHWs attempted 3,200 contacts in 530 trips. On average, 3 CHWs attempted to contact 6 participants over each 111 minute trip. The per-person cost (2003 Rand for these activities was 12.75, 24.92, and 40.50 for 6, 12, and 24-month visits. Conclusion CHW contact with women who missed scheduled visits increased their return rate. Cost-effectiveness analyses aimed at policy decisions about cervical cancer screening in developing countries should incorporate these findings.

  17. Site-specific RNase A activity was dramatically reduced in serum from multiple types of cancer patients.

    Directory of Open Access Journals (Sweden)

    Weiyan Huang

    Full Text Available Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5'-U/A-3' and 5'-C/A-3' dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10(-5 mg/ml- 10(-1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types.

  18. Site-Specific RNase A Activity Was Dramatically Reduced in Serum from Multiple Types of Cancer Patients

    Science.gov (United States)

    Huang, Weiyan; Zhao, Mei; Wei, Na; Wang, Xiaoxia; Cao, Huqing; Du, Quan; Liang, Zicai

    2014-01-01

    Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5′-U/A-3′ and 5′-C/A-3′ dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10−5 mg/ml- 10−1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types. PMID:24805924

  19. The 20-year effort to reduce access to mammography screening: historical facts dispute a commentary in Cancer.

    Science.gov (United States)

    Kopans, Daniel B; Webb, Matthew L; Cady, Blake

    2014-09-15

    Mammography screening fulfills all requirements for an effective screening test. It detects many cancers earlier when they are at a smaller size and earlier stage, and it has been demonstrated that this reduces breast cancer deaths in randomized controlled trials. When screening is introduced into the population, the death rate from breast cancer declines. Nevertheless, scientifically unsupported arguments that appear in the medical literature are passed on to the public and continue to confuse women and physicians regarding the value of screening. Methodologically flawed challenges to mammography have been almost continuous since the 1990s. And, as each challenge has been invalidated, a new, specious challenge has been raised. The authors of this report address the long history of misinformation that has developed in the effort to reduce access to screening, and they address the issues raised by commentators concerning their recent publication in this journal. © 2014 American Cancer Society.

  20. Reduced Acute Bowel Toxicity in Patients Treated With Intensity-Modulated Radiotherapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Samuelian, Jason M.; Callister, Matthew D.; Ashman, Jonathan B.; Young-Fadok, Tonia M.; Borad, Mitesh J.; Gunderson, Leonard L.

    2012-01-01

    Purpose: We have previously shown that intensity-modulated radiotherapy (IMRT) can reduce dose to small bowel, bladder, and bone marrow compared with three-field conventional radiotherapy (CRT) technique in the treatment of rectal cancer. The purpose of this study was to review our experience using IMRT to treat rectal cancer and report patient clinical outcomes. Methods and Materials: A retrospective review was conducted of patients with rectal cancer who were treated at Mayo Clinic Arizona with pelvic radiotherapy (RT). Data regarding patient and tumor characteristics, treatment, acute toxicity according to the Common Terminology Criteria for Adverse Events v 3.0, tumor response, and perioperative morbidity were collected. Results: From 2004 to August 2009, 92 consecutive patients were treated. Sixty-one (66%) patients were treated with CRT, and 31 (34%) patients were treated with IMRT. All but 2 patients received concurrent chemotherapy. There was no significant difference in median dose (50.4 Gy, CRT; 50 Gy, IMRT), preoperative vs. postoperative treatment, type of concurrent chemotherapy, or history of previous pelvic RT between the CRT and IMRT patient groups. Patients who received IMRT had significantly less gastrointestinal (GI) toxicity. Sixty-two percent of patients undergoing CRT experienced ≥Grade 2 acute GI side effects, compared with 32% among IMRT patients (p = 0.006). The reduction in overall GI toxicity was attributable to fewer symptoms from the lower GI tract. Among CRT patients, ≥Grade 2 diarrhea and enteritis was experienced among 48% and 30% of patients, respectively, compared with 23% (p = 0.02) and 10% (p = 0.015) among IMRT patients. There was no significant difference in hematologic or genitourinary acute toxicity between groups. In addition, pathologic complete response rates and postoperative morbidity between treatment groups did not differ significantly. Conclusions: In the management of rectal cancer, IMRT is associated with a

  1. EFFICACIOUS PSYCHOLOGICAL TREATMENTS FOR REDUCING FATIGUE IN CANCER SURVIVORS: THE STATE OF THE QUESTION AND FUTURE PROSPECTS

    Directory of Open Access Journals (Sweden)

    Francisco García Torres

    2015-09-01

    Full Text Available Cancer remains a major health problem worldwide. Due to the efficacy of the treatments and the improvements in healthcare systems, however, the number of cancer survivors has increased significantly over the years. Fatigue is one of the consequences of cancer that appears most frequently, causing significant changes in the lives of survivors. Different psychological treatments have been used to reduce fatigue in this patient group. Cognitive-behavioural techniques and mindfulness therapies are the ones that have the most data supporting their effectiveness, ahead of psycho-educational type interventions. The majority of studies, however, have been conducted with breast cancer survivors, and it would be desirable to test the effectiveness of these techniques with a greater variability of cancer types.

  2. Nanomolar concentration of blood-soluble drag-reducing polymer inhibits experimental metastasis of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Ding Z

    2017-02-01

    Full Text Available Zhijie Ding,1,* Marion Joy,1,* Marina V Kameneva,1-3 Partha Roy1,3-6 1Department of Bioengineering, 2Department of Surgery, 3McGowan Institute of Regenerative Medicine, 4Department of Pathology, 5Department of Cell Biology, 6Magee Women’s Research Institute, University of Pittsburgh, Pittsburgh, PA, USA *These authors contributed equally to this work Abstract: Metastasis is the leading cause of cancer mortality. Extravasation of cancer cells is a critical step of metastasis. We report a novel proof-of-concept study that investigated whether non-toxic blood-soluble chemical agents capable of rheological modification of the near-vessel-wall blood flow can reduce extravasation of tumor cells and subsequent development of metastasis. Using an experimental metastasis model, we demonstrated that systemic administration of nanomolar concentrations of so-called drag-reducing polymer dramatically impeded extravasation and development of pulmonary metastasis of breast cancer cells in mice. This is the first proof-of-principle study to directly demonstrate physical/rheological, as opposed to chemical, way to prevent cancer cells from extravasation and developing metastasis and, thus, it opens the possibility of a new direction of adjuvant interventional approach in cancer. Keywords: breast cancer, metastasis, extravasation, hemodynamics, drag-reducing polymer, blood cell traffic, microvessels

  3. [Cancer treatment in Skane and in Sjaelland. Do differences concerning examination and treatment explain reduced survival among Danish cancer patients?

    DEFF Research Database (Denmark)

    Specht, Lena; Landberg, T.

    2001-01-01

    if differences in the diagnostic workup and treatment can explain some of this variation. MATERIAL AND METHODS: Aspects of the diagnostic workup and treatment of the above mentioned four cancer types are examined using data from cancer registry analyses and official reports. These data are seen in the context...... of counts of trained personnel and equipment in cancer diagnostics and treatment in the two countries. RESULTS: With regard to lung and breast cancer, the data seem to indicate that Danish patients are diagnosed later, and that Denmark lags behind in treatment capacity. With regard to rectal cancer......, the data seem to indicate that concentrating operations in fewer hospitals, and improvements in operation technique have been introduced earlier in Sweden than in Denmark. With regard to prostate cancer, however, the data seem to indicate that many more indolent cases that do not need treatment...

  4. beta-TrCP inhibition reduces prostate cancer cell growth via upregulation of the aryl hydrocarbon receptor.

    Directory of Open Access Journals (Sweden)

    Udi Gluschnaider

    2010-02-01

    Full Text Available Prostate cancer is a common and heterogeneous disease, where androgen receptor (AR signaling plays a pivotal role in development and progression. The initial treatment for advanced prostate cancer is suppression of androgen signaling. Later on, essentially all patients develop an androgen independent stage which does not respond to anti hormonal treatment. Thus, alternative strategies targeting novel molecular mechanisms are required. beta-TrCP is an E3 ligase that targets various substrates essential for many aspects of tumorigenesis.Here we show that beta-TrCP depletion suppresses prostate cancer and identify a relevant growth control mechanism. shRNA targeted against beta-TrCP reduced prostate cancer cell growth and cooperated with androgen ablation in vitro and in vivo. We found that beta-TrCP inhibition leads to upregulation of the aryl hydrocarbon receptor (AhR mediating the therapeutic effect. This phenomenon could be ligand independent, as the AhR ligand 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD did not alter prostate cancer cell growth. We detected high AhR expression and activation in basal cells and atrophic epithelial cells of human cancer bearing prostates. AhR expression and activation is also significantly higher in tumor cells compared to benign glandular epithelium.Together these observations suggest that AhR activation may be a cancer counteracting mechanism in the prostate. We maintain that combining beta-TrCP inhibition with androgen ablation could benefit advanced prostate cancer patients.

  5. TCW: transcriptome computational workbench.

    Directory of Open Access Journals (Sweden)

    Carol Soderlund

    Full Text Available BACKGROUND: The analysis of transcriptome data involves many steps and various programs, along with organization of large amounts of data and results. Without a methodical approach for storage, analysis and query, the resulting ad hoc analysis can lead to human error, loss of data and results, inefficient use of time, and lack of verifiability, repeatability, and extensibility. METHODOLOGY: The Transcriptome Computational Workbench (TCW provides Java graphical interfaces for methodical analysis for both single and comparative transcriptome data without the use of a reference genome (e.g. for non-model organisms. The singleTCW interface steps the user through importing transcript sequences (e.g. Illumina or assembling long sequences (e.g. Sanger, 454, transcripts, annotating the sequences, and performing differential expression analysis using published statistical programs in R. The data, metadata, and results are stored in a MySQL database. The multiTCW interface builds a comparison database by importing sequence and annotation from one or more single TCW databases, executes the ESTscan program to translate the sequences into proteins, and then incorporates one or more clusterings, where the clustering options are to execute the orthoMCL program, compute transitive closure, or import clusters. Both singleTCW and multiTCW allow extensive query and display of the results, where singleTCW displays the alignment of annotation hits to transcript sequences, and multiTCW displays multiple transcript alignments with MUSCLE or pairwise alignments. The query programs can be executed on the desktop for fastest analysis, or from the web for sharing the results. CONCLUSION: It is now affordable to buy a multi-processor machine, and easy to install Java and MySQL. By simply downloading the TCW, the user can interactively analyze, query and view their data. The TCW allows in-depth data mining of the results, which can lead to a better understanding of the

  6. Psychosocial factors and uptake of risk-reducing salpingo-oophorectomy in women at high risk for ovarian cancer.

    Science.gov (United States)

    Meiser, Bettina; Price, Melanie A; Butow, Phyllis N; Karatas, Janan; Wilson, Judy; Heiniger, Louise; Baylock, Brandi; Charles, Margaret; McLachlan, Sue-Anne; Phillips, Kelly-Anne

    2013-03-01

    Bilateral risk-reducing salpingo-oophorectomy (RRSO) has been shown to significantly reduce the risk of ovarian cancer. This study assessed factors predicting uptake of RRSO. Women participating in a large multiple-case breast cancer family cohort study who were at increased risk for ovarian and fallopian tube cancer (i.e. BRCA1 or BRCA2 mutation carrier or family history including at least one first- or second-degree relative with ovarian or fallopian tube cancer), with no personal history of cancer and with at least one ovary in situ at cohort enrolment, were eligible for this study. Women who knew they did not carry the BRCA1 or BRCA2 mutation segregating in their family (true negatives) were excluded. Sociodemographic, biological and psychosocial factors, including cancer-specific anxiety, perceived ovarian cancer risk, optimism and social support, were assessed using self-administered questionnaires and interviews at cohort enrolment. RRSO uptake was self-reported every three years during systematic follow-up. Of 2,859 women, 571 were eligible. Mean age was 43.3 years; 62 women (10.9 %) had RRSO a median of two years after cohort entry. Factors predicting RRSO were: being parous (OR 3.3, p = 0.015); knowing one's mutation positive status (OR 2.9, p cancer (OR 2.5, p = 0.013). Psychological variables measured at cohort entry were not associated with RRSO. These results suggest that women at high risk for ovarian cancer make decisions about RRSO based on risk and individual socio-demographic characteristics, rather than in response to psychological factors such as anxiety.

  7. Reducing Xerostomia After Chemo-IMRT for Head and Neck Cancer: Beyond Sparing the Parotid Glands

    Science.gov (United States)

    Little, Michael; Schipper, Matthew; Feng, Felix Y.; Vineberg, Karen; Cornwall, Craig; Murdoch-Kinch, Carol-Anne; Eisbruch, Avraham

    2011-01-01

    Purpose To assess whether in addition to sparing parotid glands (PGs), xerostomia after chemo-IMRT of head and neck cancer is affected by reducing doses to other salivary glands. Methods Prospective study: 78 patients with stages III/IV oropharynx/nasopharynx cancers received chemo-IMRT aiming to spare the parts outside the targets of bilateral PGs, oral cavity (OC) containing the minor salivary glands, and contralateral submandibular gland (SMG) (when contralateral level I was not a target). Pretherapy and periodically through 24 months, validated patient-reported xerostomia questionnaires (XQ) scores and observer-graded xerostomia were recorded, and stimulated and unstimulated saliva measured selectively from each of the PGs and SMGs. Mean OC doses served as surrogates of minor salivary glands dysfunction. Regression models assessed XQ and observer-graded xerostomia predictors. Results Statistically significant predictors of the XQ score in univariate analysis included OC, PG, and SMG mean doses, as well as baseline XQ score, time since RT, and both stimulated and unstimulated PG saliva flow rates. Similar factors were statistically significant predictors of observer-graded xerostomia. OC, PG and SMG mean doses were moderately inter-correlated (r=0.47–0.55). In multivariate analyses, after adjusting for PG and SMG doses, OC mean dose (p xerostomia. While scatter plots showed no thresholds, OC mean doses xerostomia at almost all post-therapy time points. Conclusion PG, SMG and OC mean doses were significant predictors of both patient-reported and observer-rated xerostomia after chemo-IMRT, with OC doses remaining significant after adjusting for PG and SMG doses. These results support efforts to spare all salivary glands by IMRT, beyond the PGs alone. PMID:22056067

  8. Rye bread consumption in early life and reduced risk of advanced prostate cancer.

    Science.gov (United States)

    Torfadottir, Johanna E; Valdimarsdottir, Unnur A; Mucci, Lorelei; Stampfer, Meir; Kasperzyk, Julie L; Fall, Katja; Tryggvadottir, Laufey; Aspelund, Thor; Olafsson, Orn; Harris, Tamara B; Jonsson, Eirikur; Tulinius, Hrafn; Adami, Hans-Olov; Gudnason, Vilmundur; Steingrimsdottir, Laufey

    2012-06-01

    To determine whether consumption of whole-grain rye bread, oatmeal, and whole-wheat bread, during different periods of life, is associated with risk of prostate cancer (PCa). From 2002 to 2006, 2,268 men, aged 67-96 years, reported their dietary habits in the AGES-Reykjavik cohort study. Dietary habits were assessed for early life, midlife, and current life using a validated food frequency questionnaire. Through linkage to cancer and mortality registers, we retrieved information on PCa diagnosis and mortality through 2009. We used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for PCa according to whole-grain consumption, adjusted for possible confounding factors including fish, fish liver oil, meat, and milk intake. Of the 2,268 men, 347 had or were diagnosed with PCa during follow-up, 63 with advanced disease (stage 3+ or died of PCa). Daily rye bread consumption in adolescence (vs. less than daily) was associated with a decreased risk of PCa diagnosis (OR = 0.76, 95 % confidence interval (CI): 0.59-0.98) and of advanced PCa (OR = 0.47, 95 % CI: 0.27-0.84). High intake of oatmeal in adolescence (≥5 vs. ≤4 times/week) was not significantly associated with risk of PCa diagnosis (OR = 0.99, 95 % CI: 0.77-1.27) nor advanced PCa (OR = 0.67, 95 % CI: 0.37-1.20). Midlife and late life consumption of rye bread, oatmeal, or whole-wheat bread was not associated with PCa risk. Our results suggest that rye bread consumption in adolescence may be associated with reduced risk of PCa, particularly advanced disease.

  9. Tobacco control: reducing cancer incidence and saving lives. American Society of Clinical Oncology.

    Science.gov (United States)

    1996-06-01

    The American Society of Clinical Oncology (ASCO) supports the elimination of tobacco products. Toward that goal, ASCO urges the adoption of national policy that strengthens regulation of the sale, promotion, and distribution of such products. To reduce cancer mortality, our regulatory policies must recognize that the nicotine within tobacco is an addictive substance, the use of which leads to 30% of all cancer deaths and a total of 419,000 deaths each year. Tobacco-related advertising and promotion should be banned. At a minimum, national policies should: ban billboards; limit advertising to black and white text only; prohibit the sale or giveaway of products that contain tobacco brand names or logos; prohibit brand name sponsorship of sporting or entertainment events; and require stronger and more prominent warning labels on all tobacco products. Despite existing state laws prohibiting sale of tobacco products to minors, children are able to buy such products easily. National regulation of the sale and distribution of tobacco products is necessary to eliminate children's access to tobacco. Where sales are permitted, they should be limited to face-to-face purchases by individuals 18 and older. Vending machines and other means of distributing tobacco without a face-to-face purchase should be outlawed. To the extent tobacco sales are allowed to continue, the federal government should mandate that the tobacco industry contribute substantial funds for a national public education campaign to prevent young people from smoking and other tobacco use. ASCO has long advocated a substantial increase (in the range of $2) in the federal excise tax on cigarettes and other tobacco products- a measure known to decrease consumption, particularly among children. Revenue from a tax on tobacco products should be used to support retraining for tobacco farmers, biomedical research, health care delivery, and antitobacco education. United State trade policies should discourage the export

  10. NIH Study Finds Regular Aspirin Use May Reduce Ovarian Cancer Risk

    Science.gov (United States)

    ... Links PubMed Stem Cell Information OppNet NIDB NIH Blueprint for Neuroscience Research Institutes at NIH List of ... www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422- ...

  11. Study shows aspirin reduces the risk and recurrence of prostate cancer in African-American men | Center for Cancer Research

    Science.gov (United States)

    African-American men who take a daily dose of aspirin experience a significantly lower risk of developing advanced prostate cancer – the aggressive and deadly form of the disease – than African-American men who do not regularly use aspirin, according to a study from the Center for Cancer Research (CCR) Laboratory of Human Carcinogenesis. Learn more...

  12. Minocycline Hydrochloride in Reducing Chemotherapy Induced Depression and Anxiety in Patients With Stage I-III Breast Cancer

    Science.gov (United States)

    2017-08-07

    Anxiety Disorder; Depression; Recurrent Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

  13. Synergistic effect of shape-selective silver nanostructures decorating reduced graphene oxide nanoplatelets for enhanced cytotoxicity against breast cancer

    Science.gov (United States)

    Derakhshi, Maryam; Ashkarran, Ali Akbar; Bahari, Ali; Bonakdar, Shahin

    2018-07-01

    Graphene-based nanomaterials contain unique physicochemical properties and have been widely investigated due to a variety of applications particularly in cancer therapy. Furthermore, Ag has been known for its extensive historical background for biomedical applications. Therefore, conjugation of shape-selective Ag nanostructures with graphene may provide new horizons for pharmaceutical applications such as cancer treatments. Here we report on the synthesis of Ag nanoparticles (NPs)/reduced graphene oxide (AgNPs/RGO) conjugate nanomaterials containing various shapes of AgNPs by a novel and simple synthesis route using the deformation of dimethylformamide (DMF) as the reducing and coupling agent. The cytotoxicity and anticancer properties of AgNPs, AgNPs/RGO conjugate nanomaterials, RGO and graphene oxide (GO) were probed against MDA-MB-231 cancer and MCF-10A normal human breast cells in vitro. The AgNPs/RGO nanocomposites exhibited a strong anticancer effect by penetration and apoptosis in cancer cells as well as the lowest influence on the viability of normal cells. It was found that cancer cell viability not only depends on the geometry of Ag nanostructures but also on the interaction between AgNPs and RGO nanoplatelets. It is suggested that AgNPs/RGO conjugate nanomaterials with various shapes of AgNPs is a promising therapeutic platform for cancer therapy.

  14. HPV16 early gene E5 specifically reduces miRNA-196a in cervical cancer cells

    Science.gov (United States)

    Liu, Chanzhen; Lin, Jianfei; Li, Lianqin; Zhang, Yonggang; Chen, Weiling; Cao, Zeyi; Zuo, Huancong; Chen, Chunling; Kee, Kehkooi

    2015-01-01

    High-risk human papillomavirus (HPV) type 16, which is responsible for greater than 50% of cervical cancer cases, is the most prevalent and lethal HPV type. However, the molecular mechanisms of cervical carcinogenesis remain elusive, particularly the early steps of HPV infection that may transform normal cervical epithelium into a pre-neoplastic state. Here, we report that a group of microRNAs (microRNAs) were aberrantly decreased in HPV16-positive normal cervical tissues, and these groups of microRNAs are further reduced in cervical carcinoma. Among these miRNAs, miR196a expression is the most reduced in HPV16-infected tissues. Interestingly, miR196a expression is low in HPV16-positive cervical cancer cell lines but high in HPV16-negative cervical cancer cell lines. Furthermore, we found that only HPV16 early gene E5 specifically down-regulated miRNA196a in the cervical cancer cell lines. In addition, HoxB8, a known miR196a target gene, is up-regulated in the HPV16 cervical carcinoma cell line but not in HPV18 cervical cancer cell lines. Various doses of miR196a affected cervical cancer cell proliferation and apoptosis. Altogether, these results suggested that HPV16 E5 specifically down-regulates miR196a upon infection of the human cervix and initiates the transformation of normal cervix cells to cervical carcinoma. PMID:25563170

  15. Perceptions of Risk of Developing Skin Cancer for Diverse Audiences: Enhancing Relevance of Sun Protection to Reduce the Risk.

    Science.gov (United States)

    Robinson, June K; Friedewald, John; Gordon, Elisa J

    2016-03-01

    Sixty-five percent of kidney transplant recipients (KTRs) develop squamous cell carcinoma (SCC). Perceptions of risk of developing skin cancer, amelioration of this risk with sun protection, and having choices among sun protection strategies may enhance sun protection use by KTRS, who are at greater risk than the general population. Thirty KTRs stratified among non-Hispanic Whites, non-Hispanic Blacks, and Hispanic/Latinos evaluated three versions of the interactive, web-based, electronic sun protection program and suggested refinements. The sequence of content presentation prepared the participant to accept the credibility, accuracy, and relevance of the message. Beginning with informing participants that using sun protection reduces the chance of developing skin cancer made the information credible to KTRs. Showing skin cancer on all skin types and patient testimonials enhanced participants' awareness of their susceptibility to develop skin cancer and primed patients to receive their personal risk of developing skin cancer. Coupling presentation of knowledge about the benefits of sun protection in reducing the risk of developing skin cancer with the personal risk of getting the disease was essential to KTRs believing that they could influence their health outcome.

  16. Evaluating proton stereotactic body radiotherapy to reduce chest wall dose in the treatment of lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Welsh, James, E-mail: jwelsh@mdanderson.org [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Amini, Arya [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); UC Irvine School of Medicine, Irvine, CA (United States); Ciura, Katherine; Nguyen, Ngoc; Palmer, Matt [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Soh, Hendrick [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Department of Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Allen, Pamela K.; Paolini, Michael; Liao, Zhongxing [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Bluett, Jaques; Mohan, Radhe [Department of Radiation Physics, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States); Gomez, Daniel; Cox, James D.; Komaki, Ritsuko; Chang, Joe Y. [Department of Radiation Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX (United States)

    2013-01-01

    Stereotactic body radiotherapy (SBRT) can produce excellent local control of several types of solid tumor; however, toxicity to nearby critical structures is a concern. We found previously that in SBRT for lung cancer, the chest wall (CW) volume receiving 20, 30, or 40 Gy (V{sub 20}, V{sub 30}, or V{sub 40}) was linked with the development of neuropathy. Here we sought to determine whether the dosimetric advantages of protons could produce lower CW doses than traditional photon-based SBRT. We searched an institutional database to identify patients treated with photon SBRT for lung cancer with tumors within < 2.5 cm of the CW. We found 260 cases; of these, chronic grade ≥ 2 CW pain was identified in 23 patients. We then selected 10 representative patients from this group and generated proton SBRT treatment plans, using the identical dose of 50 Gy in 4 fractions, and assessed potential differences in CW dose between the 2 plans. The proton SBRT plans reduced the CW doses at all dose levels measured. The median CW V{sub 20} was 364.0 cm{sup 3} and 160.0 cm{sup 3} (p < 0.0001), V{sub 30} was 144.6 cm{sup 3}vs 77.0 cm{sup 3} (p = 0.0012), V{sub 35} was 93.9 cm{sup 3}vs 57.9 cm{sup 3} (p = 0.005), V{sub 40} was 66.5 cm{sup 3}vs 45.4 cm{sup 3} (p = 0.0112), and mean lung dose was 5.9 Gy vs 3.8 Gy (p = 0.0001) for photons and protons, respectively. Coverage of the planning target volume (PTV) was comparable between the 2 sets of plans (96.4% for photons and 97% for protons). From a dosimetric standpoint, proton SBRT can achieve the same coverage of the PTV while significantly reducing the dose to the CW and lung relative to photon SBRT and therefore may be beneficial for the treatment of lesions closer to critical structures.

  17. MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels.

    Science.gov (United States)

    Lu, Yunqi; Hu, Zhongyi; Mangala, Lingegowda S; Stine, Zachary E; Hu, Xiaowen; Jiang, Dahai; Xiang, Yan; Zhang, Youyou; Pradeep, Sunila; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; DeMarzo, Angelo M; Sood, Anil K; Zhang, Lin; Dang, Chi V

    2018-01-01

    The MYC oncogene broadly promotes transcription mediated by all nuclear RNA polymerases, thereby acting as a positive modifier of global gene expression. Here, we report that MYC stimulates the transcription of DANCR, a long noncoding RNA (lncRNA) that is widely overexpressed in human cancer. We identified DANCR through its overexpression in a transgenic model of MYC-induced lymphoma, but found that it was broadly upregulated in many human cancer cell lines and cancers, including most notably in prostate and ovarian cancers. Mechanistic investigations indicated that DANCR limited the expression of cell-cycle inhibitor p21 (CDKN1A) and that the inhibitory effects of DANCR loss on cell proliferation could be partially rescued by p21 silencing. In a xenograft model of human ovarian cancer, a nanoparticle-mediated siRNA strategy to target DANCR in vivo was sufficient to strongly inhibit tumor growth. Our observations expand knowledge of how MYC drives cancer cell proliferation by identifying DANCR as a critical lncRNA widely overexpressed in human cancers. Significance: These findings expand knowledge of how MYC drives cancer cell proliferation by identifying an oncogenic long noncoding RNA that is widely overexpressed in human cancers. Cancer Res; 78(1); 64-74. ©2017 AACR . ©2017 American Association for Cancer Research.

  18. Reducing Racial Disparities in Breast Cancer Care: The Role of 'Big Data'.

    Science.gov (United States)

    Reeder-Hayes, Katherine E; Troester, Melissa A; Meyer, Anne-Marie

    2017-10-15

    Advances in a wide array of scientific technologies have brought data of unprecedented volume and complexity into the oncology research space. These novel big data resources are applied across a variety of contexts-from health services research using data from insurance claims, cancer registries, and electronic health records, to deeper and broader genomic characterizations of disease. Several forms of big data show promise for improving our understanding of racial disparities in breast cancer, and for powering more intelligent and far-reaching interventions to close the racial gap in breast cancer survival. In this article we introduce several major types of big data used in breast cancer disparities research, highlight important findings to date, and discuss how big data may transform breast cancer disparities research in ways that lead to meaningful, lifesaving changes in breast cancer screening and treatment. We also discuss key challenges that may hinder progress in using big data for cancer disparities research and quality improvement.

  19. Gastric washing by distilled water can reduce free gastric cancer cells exfoliated into the stomach lumen.

    Science.gov (United States)

    Ohki, Atsuko; Abe, Nobutsugu; Yoshimoto, Eri; Hashimoto, Yoshikazu; Takeuchi, Hirohisa; Nagao, Gen; Masaki, Tadahiko; Mori, Toshiyuki; Ohkura, Yasuo; Sugiyama, Masanori

    2018-04-25

    Intragastric free cancer cells in patients with gastric cancer have rarely been studied. The purpose of this study was to investigate the detection rate of intragastric free cancer cells in gastric washes using two types of solutions during endoscopic examination. We further clarified risk factors affecting the presence of exfoliated free cancer cells. A total of 175 patients with gastric cancer were enrolled. Lactated Ringer's solution (N = 89) or distilled water (DW; N = 86) via endoscopic working channel was sprayed onto the tumor surface, and the resultant fluid was collected for cytological examination. We compared the cancer-cell positivity rate between the two (Ringer and DW) groups. We also tested the correlation between cancer-cell positivity and clinicopathological factors in the Ringer group to identify risk factors for the presence of exfoliated cancer cells. The cancer-cell positivity rate was significantly higher in the Ringer group than that in the DW group (58 vs 6%). Cytomorphology in the Ringer group was well maintained, but not in the DW group. The larger tumor size (≥ 20 mm) and positive lymphatic involvement were significant risk factors of exfoliated free cancer cells. Cancer cells can be highly exfoliated from the tumor surface into the gastric lumen by endoscopic irrigation in large gastric cancer with lymphatic involvement. Gastric washing by DW can lead to cytoclasis of free cancer cells; therefore, it may minimize the possibility of cancer-cell seeding in procedures carrying potential risks of tumor-cell seeding upon transluminal communication, such as endoscopic full-thickness resection and laparoscopy-endoscopy cooperative surgery.

  20. Hydrogel injection reduces rectal toxicity after radiotherapy for localized prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pinkawa, Michael; Berneking, Vanessa; Koenig, Liane; Frank, Dilini; Bretgeld, Marilou; Eble, Michael J. [RWTH Aachen University, Department of Radiation Oncology, Aachen (Germany)

    2017-01-15

    Injection of a hydrogel spacer before prostate cancer radiotherapy (RT) is known to reduce the dose to the rectal wall. Clinical results from the patient's perspective are needed to better assess a possible benefit. A group of 167 consecutive patients who received prostate RT during the years 2010 to 2013 with 2-Gy fractions up to 76 Gy (without hydrogel, n = 66) or 76-80 Gy (with hydrogel, n = 101) were included. The numbers of interventions resulting from bowel problems during the first 2 years after RT were compared. Patients were surveyed prospectively before RT, at the last day of RT, and at a median of 2 and 17 months after RT using a validated questionnaire (Expanded Prostate Cancer Index Composite). Baseline patient characteristics were well balanced. Treatment for bowel symptoms (0 vs. 11 %; p < 0.01) and endoscopic examinations (3 vs. 19 %; p < 0.01) were performed less frequently with a spacer. Mean bowel function scores did not change for patients with a spacer in contrast to patients without a spacer (mean decrease of 5 points) >1 year after RT in comparison to baseline, with 0 vs. 12 % reporting a new moderate/big problem with passing stools (p < 0.01). Statistically significant differences were found for the items ''loose stools'', ''bloody stools'', ''painful bowel movements'' and ''frequency of bowel movements''. Spacer injection is associated with a significant benefit for patients after prostate cancer RT. (orig.) [German] Bei der Radiotherapie (RT) des Prostatakarzinoms kann die Dosis an der Rektumwand durch die Injektion eines Hydrogelabstandhalters gesenkt werden. Klinische Ergebnisse aus der Sicht des Patienten sind zur Einschaetzung eines moeglichen Vorteils erforderlich. Eine Gruppe von 167 konsekutiven Patienten, die in den Jahren 2010-2013 eine Prostata-RT mit Einzeldosen von 2 bis 76 Gy (ohne Hydrogel, n = 66) bzw. 76-80 Gy (mit Hydrogel, n = 101

  1. Simple shielding reduces dose to the contralateral breast during prone breast cancer radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Goyal, Uma, E-mail: uma.goyal@gmail.com; Locke, Angela; Smith-Raymond, Lexie; Georgiev, Georgi N.

    2016-07-01

    shielded dose means were 12.68 and 1.54 cGy, respectively. When comparing medial and lateral portions of the contralateral bolus-based doses without and with Pb, the shield significantly reduced dose to both sides of the contralateral breast (medial p = 2.64 × 10{sup −14}, lateral p = 4.91 × 10{sup −6}). The prone 0.2-cm Pb shield significantly reduced scatter dose to the contralateral breast on the order of 2 to 3 times. Reductions may be clinically relevant for women younger than 45 years by decreasing the risk of contralateral radiation-induced breast cancer in patients receiving radiation therapy for breast cancer. This shield is simple as it would be a part of the prone breast board during treatments, but future studies are warranted for safety and efficacy clinically.

  2. Interventions targeting absences increase adherence and reduce abandonment of childhood cancer treatment in El Salvador.

    Science.gov (United States)

    Salaverria, Carmen; Rossell, Nuria; Hernandez, Angelica; Fuentes Alabi, Soad; Vasquez, Roberto; Bonilla, Miguel; Lam, Catherine G; Ribeiro, Raul C

    2015-09-01

    In El Salvador, about 200 new cases of pediatric cancer are diagnosed each year, and survival rates approach 70%. Although treatment is available at no cost, abandonment of therapy has remained at a steady yearly rate of 13% during the past decade. A time sensitive adherence tracking procedure (TS-ATP) was recently implemented to detect missed appointments, identify their causes, and intervene promptly. Procedure The study team was informed daily of patient/family failure to attend medical appointments in the pediatric oncology unit; the families were contacted and interviewed to ascertain and address the reasons. Patients who did not return after this initial contact were contacted again through local health clinics and municipalities. Law enforcement was a last resort for patients undergoing frontline treatment with a good prognosis., The system was adapted to clinical urgency: families of patients undergoing induction therapy were contacted within 24 hr, those in other therapy phases, within 48 hr, and those who had completed treatment, within one week. Reasons for absence were obtained by telephone or in person. The annual rate of abandonment was reduced from 13-3% during the 2 years period. There were 1,111 absences reported and 1,472 contacts with caregivers and institutions. The three main reasons for absences were financial needs (165, 23%), unforeseen barriers (116, 16%), and domestic needs (86, 12%). Use of the treatment adherence tracking system to locate and communicate with patients/families after missed appointments and the allocated aid stemming from these interviews substantially reduced abandonment and non-adherence. © 2015 Wiley Periodicals, Inc.

  3. Reduced dose of salvage-line regorafenib monotherapy for metastatic colorectal cancer in Japan.

    Science.gov (United States)

    Hirano, Gen; Makiyama, Akitaka; Makiyama, Chinatsu; Esaki, Taito; Oda, Hisanobu; Uchino, Keita; Komoda, Masato; Tanaka, Risa; Matsushita, Yuzo; Mitsugi, Kenji; Shibata, Yoshihiro; Kumagai, Hozumi; Arita, Shuji; Ariyama, Hiroshi; Kusaba, Hitoshi; Akashi, Koichi; Baba, Eishi

    2015-01-01

    Salvage-line regorafenib monotherapy exhibited a marked survival benefit for metastatic colorectal cancer (mCRC). However, the toxicity of this regimen has resulted in the clinical use of a reduced dose of regorafenib. Thirty-two Japanese mCRC patients (median age=61 years) who had been treated with regorafenib were retrospectively examined. Best objective response rate was 0% and stable disease (SD) was 31%. Median progression-free survival was 81 days and median overall survival was 233 days. Adverse events of any grade were observed in all patients: 17 (53%) patients suffered grade 3 or 4 adverse events including fatigue (13%), anorexia (13%), hand-foot skin reaction (22%) and elevations of alanine aminotransferase/aspartate aminotransferase (19%/16%). One patient with grade 5 liver dysfunction was identified (3%). Twenty-nine (91%) patients required treatment dose reduction or a delay in treatment. The relative dose intensity was 59%. Regorafenib treatments were terminated because of disease progression (59%) or adverse events (34%). Despite a decrease in the intensity of regorafenib treatment, because of severe adverse events, a fairly favorable efficacy was achieved in Japanese patients. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Shikonin Inhibits the Proliferation of Human Breast Cancer Cells by Reducing Tumor-Derived Exosomes

    Directory of Open Access Journals (Sweden)

    Yao Wei

    2016-06-01

    Full Text Available Shikonin is a naphthoquinone isolated from the traditional Chinese medicine Lithospermum. It has been used in the treatment of various tumors. However, the effects of shikonin on such diseases have not been fully elucidated. In the present study, we detected the exosome release of a breast cancer cell line (MCF-7 with shikonin treatment and found a positive relationship between the level of secreted exosomes and cell proliferation. We next analyzed miRNA profiles in MCF-7 cells and exosomes and found that some miRNAs are specifically sorted and abundant in exosomes. Knockdown of the most abundant miRNAs in exosomes and the MCF-7 proliferation assay showed that miR-128 in exosomes negatively regulates the level of Bax in MCF-7 recipient cells and inhibits cell proliferation. These results show that shikonin inhibits the proliferation of MCF-7 cells through reducing tumor-derived exosomal miR-128. The current study suggests that shikonin suppresses MCF-7 growth by the inhibition of exosome release.

  5. Right Sided Colon Cancer as a Distinct Histopathological Subtype with Reduced Prognosis.

    Science.gov (United States)

    Nitsche, Ulrich; Stögbauer, Fabian; Späth, Christoph; Haller, Bernhard; Wilhelm, Dirk; Friess, Helmut; Bader, Franz G

    2016-01-01

    Recent data suggest that tumors of the right and left colon should be distinguished as they differ in clinical and molecular characteristics. A total of 1,319 patients who underwent surgical resection for colon cancer (CC) were investigated. Tumors between the ileocecal valve and the hepatic flexure were classified as right CC (RCC), tumors between the splenic flexure and the rectum as left CC (LCC). RCC revealed a higher cause-specific mortality risk (hazard ratio 1.36, 95% CI 1.10-1.68, p = 0.005) and lower 5-year cause-specific (RCC 64.9%, 95% CI 60.4-69.4, LCC 70.7%, 95% CI 67.2-74.2, p = 0.032) and disease-free (RCC 56.0%, 95% CI 51.5-60.5, LCC 59.9%, 95% CI 56.2-63.6, p = 0.025) survival rates. RCCs were more often microsatellite instable (RCC 37.2%, LCC 13.0%, p clinical, histopathological and molecular genetic features and can be considered as distinct entities. The reduced prognosis of RCC may be caused by higher rates of microsatellite instability, KRAS and BRAF mutations. © 2016 S. Karger AG, Basel.

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

    Science.gov (United States)

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

    2014-01-01

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

  7. The Mediterranean Diet Reduces the Risk and Mortality of the Prostate Cancer: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Cristiano Capurso

    2017-08-01

    Full Text Available Prostate cancer is the second most common cancer in the world among men, and is the fifth most common cause of cancer death among men. The aim of our review was to analyze observational and case–control studies to point out the effects of overweight and diets components on the cancer risk, particularly on risk of prostate cancer, and the effect of the Mediterranean diet (MD on the reduction of risk and mortality of prostate cancer. It is known that incidence and progression of cancer is multifactorial. Cancer of the large bowel, breast, endometrium, and prostate are due also to a high body mass index and to high consumption of high carcinogenic dietary factors, as red and processed meat or saturated fats rich foods, and to a low consumption of vegetables and fruits. Previous meta-analysis suggested that high adherence to diet model based on the traditional MD pattern gives a significant protection from incidence and mortality of cancer of all types. The main component of the MD is olive oil, consumed in high amount by Mediterranean basin populations. In addition, phenolic compounds exert some strong chemo-preventive effects, which are due to several mechanisms, including both antioxidant effects and actions on cancer cell signaling and cell cycle progression and proliferation. The protective effect of the MD against the prostate cancer is also due to the high consumption of tomato sauce. Lycopene is the most relevant functional component in tomatoes; after activating by the cooking of tomato sauce, it exerts antioxidant properties by acting in the modulation of downregulation mechanisms of the inflammatory response. MD, therefore, represents a healthy dietary pattern in the context of a healthy lifestyle habits. In conclusion, our narrative review allows us to reaffirm how nutritional factors play an important role in cancer initiation and development, and how a healthy dietary pattern represented by MD and its components, especially olive oil

  8. Low-Dose Aspirin Reduces Breast Cancer Risk in Women with Diabetes: A Nationwide Retrospective Cohort Study in Taiwan.

    Science.gov (United States)

    Yang, Yi-Sun; Kornelius, Edy; Chiou, Jeng-Yuan; Lai, Yung-Rung; Lo, Shih-Chang; Peng, Chiung-Huei; Huang, Chien-Ning

    2017-12-01

    Low-dose aspirin is commonly used for preventing cardiovascular disease in people with diabetes, but its association with cancer remains controversial. This study used a nationwide population-based reimbursement database to investigate the relationship between low-dose aspirin use and breast cancer incidence in women with diabetes. This retrospective cohort study was conducted using data retrieved from the National Health Insurance Research Database in Taiwan from January 1, 1998 to December 31, 2011. Women diagnosed as having diabetes with low-dose aspirin use (75-165 mg daily) were identified as the study population, whereas those without low-dose aspirin use were selected as the comparison group. We analyzed 148,739 patients with diabetes. Their mean age (standard deviation) was 63.3 (12.8) years. A total of 27,378 patients were taking aspirin. Overall, the use of aspirin in patients with diabetes reduced the risk of breast cancer by 18% (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.94) after adjustment for potential confounders, namely age and comorbidities. Specifically, a cumulative dose of aspirin exceeding 88,900 mg was observed to reduce the risk of breast cancer by 47% (HR, 0.53, 95% CI, 0.43-0.67); however, low (aspirin did not reduce the risk of breast cancer. Our findings suggest that a cumulative aspirin dosage of more than 88,900 mg daily was associated with a reduced risk of breast cancer in women with diabetes. However, additional studies are necessary to confirm these findings.

  9. Effectiveness of Mindfulness-based Therapy for Reducing Anxiety and Depression in Patients With Cancer

    OpenAIRE

    Zhang, Mei-Fen; Wen, Yong-Shan; Liu, Wei-Yan; Peng, Li-Fen; Wu, Xiao-Dan; Liu, Qian-Wen

    2015-01-01

    Abstract Anxiety and depression are common among patients with cancer, and are often treated with psychological interventions including mindfulness-based therapy. The aim of the study was to perform a meta-analysis of the effectiveness of mindfulness-based interventions for improving anxiety and depression in patients with cancer. Medline, the Cochrane Library, EMBASE, and Google Scholar were searched. The randomized controlled trials designed for patients diagnosed with cancer were included....

  10. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

    OpenAIRE

    ZHAO, BING; HU, MENGCAI

    2013-01-01

    Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa...

  11. Effectiveness of a social marketing media campaign to reduce oral cancer racial disparities.

    Science.gov (United States)

    Watson, Jennifer M; Tomar, Scott L; Dodd, Virginia; Logan, Henrietta L; Choi, Youjin

    2009-08-01

    The purpose of this study was to provide a systematic evaluation of a theory-driven oral cancer awareness media campaign. We surveyed a cohort of residents in an intervention city (250) and a control city (250) immediately prior to and after the media campaign. Participants (125 black/African American and 125 white) in each city completed surveys at baseline and follow-up. Oral cancer campaign awareness was assessed in both cities, along with 4 hypothetical health campaigns. Oral cancer awareness, oral cancer exam awareness, intent to receive an oral cancer exam, interest in exam, and receipt of exam were also assessed in both cities, both at baseline and follow-up. Intervention city residents showed a significant increase in recognition of the campaign, awareness of the oral cancer exam, and interest in getting an exam, while no significant changes in those topics were found for the control city. Blacks/African Americans in the intervention city were significantly more likely than whites to demonstrate increases in awareness of the campaign, oral cancer awareness, and interest in receiving an oral cancer exam. A theory-driven media campaign was successful in increasing awareness of the oral cancer exam and interest in the exam among blacks/African Americans.

  12. Reducing time-to-treatment in underserved Latinas with breast cancer: the Six Cities Study.

    Science.gov (United States)

    Ramirez, Amelie; Perez-Stable, Eliseo; Penedo, Frank; Talavera, Gregory; Carrillo, J Emilio; Fernández, María; Holden, Alan; Munoz, Edgar; San Miguel, Sandra; Gallion, Kipling

    2014-03-01

    The interaction of clinical and patient-level challenges following a breast cancer diagnosis can be a significant source of health care disparities. Failure to address specific cultural features that create or exacerbate barriers can lead to less-than optimal navigation results, specifically in Hispanic/Latino women. To address these disparities, the study leaders in San Antonio, Texas, and 5 other regional partners of the federally-funded Redes En Acción: The National Latino Cancer Research Network developed a culturally-tailored patient navigation intervention model for Latinas with breast cancer. Compared with control patients, a higher percentage of navigated subjects initiated treatment within 30 days (69.0% versus 46.3%, P = .029) and 60 days (97.6% versus 73.1%, P = .001) following their cancer diagnosis. Time from cancer diagnosis to first treatment was lower in the navigated group (mean, 22.22 days; median, 23.00 days) than controls (mean, 48.30 days; median, 33.00 days). These results were independent of cancer stage at diagnosis and numerous characteristics of cancer clinics and individual participants. Successful application of patient navigation increased the percentage of Latinas initiating breast cancer treatment within 30 and 60 days of diagnosis. This was achieved through navigator provision of services such as accompaniment to appointments, transportation arrangements, patient telephone support, patient-family telephone support, Spanish-English language translation, and assistance with insurance paperwork. © 2013 American Cancer Society.

  13. HIF1α deficiency reduces inflammation in a mouse model of proximal colon cancer

    Directory of Open Access Journals (Sweden)

    Dessislava N. Mladenova

    2015-09-01

    Full Text Available Hypoxia-inducible factor 1α (HIF1α is a transcription factor that regulates the adaptation of cells to hypoxic microenvironments, for example inside solid tumours. Stabilisation of HIF1α can also occur in normoxic conditions in inflamed tissue or as a result of inactivating mutations in negative regulators of HIF1α. Aberrant overexpression of HIF1α in many different cancers has led to intensive efforts to develop HIF1α-targeted therapies. However, the role of HIF1α is still poorly understood in chronic inflammation that predisposes the colon to carcinogenesis. We have previously reported that the transcription of HIF1α is upregulated and that the protein is stabilised in inflammatory lesions that are caused by the non-steroidal anti-inflammatory drug (NSAID sulindac in the mouse proximal colon. Here, we exploited this side effect of long-term sulindac administration to analyse the role of HIF1α in colon inflammation using mice with a Villin-Cre-induced deletion of Hif1α exon 2 in the intestinal epithelium (Hif1αΔIEC. We also analysed the effect of sulindac sulfide on the aryl hydrocarbon receptor (AHR pathway in vitro in colon cancer cells. Most sulindac-treated mice developed visible lesions, resembling the appearance of flat adenomas in the human colon, surrounded by macroscopically normal mucosa. Hif1αΔIEC mice still developed lesions but they were smaller than in the Hif1α-floxed siblings (Hif1αF/F. Microscopically, Hif1αΔIEC mice had significantly less severe colon inflammation than Hif1αF/F mice. Molecular analysis showed reduced MIF expression and increased E-cadherin mRNA expression in the colon of sulindac-treated Hif1αΔIEC mice. However, immunohistochemistry analysis revealed a defect of E-cadherin protein expression in sulindac-treated Hif1αΔIEC mice. Sulindac sulfide treatment in vitro upregulated Hif1α, c-JUN and IL8 expression through the AHR pathway. Taken together, HIF1α expression augments inflammation

  14. β-Elemene Reverses Chemoresistance of Breast Cancer Cells by Reducing Resistance Transmission via Exosomes

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2015-07-01

    Full Text Available Background: Currently, exosomes that act as mediators of intercellular communication are being researched extensively. Our previous studies confirmed that these exosomes contain microRNAs (miRNAs that could alter chemo-susceptibility, which is partly attributed to the successful intercellular transfer of multidrug resistance (MDR-specific miRNAs. We also confirmed that β-elemene could influence MDR-related miRNA expression and regulate the expression of the target genes PTEN and Pgp, which may lead to the reversal of the chemoresistant breast cancer (BCA cells. We are the first to report these findings, and we propose the following logical hypothesis: β-elemene can mediate MDR-related miRNA expression in cells, thereby affecting the exosome contents, reducing chemoresistance transmission via exosomes, and reversing the drug resistance of breast cancer cells. Methods: MTT-cytotoxic, miRNA microarray, real-time quantitative PCR, Dual Luciferase Activity Assay, and Western blot analysis were performed to investigate the impact of β-elemene on the expression of chemoresistance specific miRNA and PTEN as well as Pgp in chemoresistant BCA exosomes. Results: Drug resistance can be reversed by β-elemene related to exosomes. There were 104 differentially expressed miRNAs in the exosomes of two chemoresistant BCA cells: adriacin (Adr - resistant MCF-7 cells (MCF-7/Adr and docetaxel (Doc - resistant MCF-7 cells (MCF-7/Doc that underwent treatment. Of these, 31 miRNAs were correlated with the constant changes in the MDR. The expression of miR-34a and miR-452 can lead to changes in the characteristics of two chemoresistant BCA exosomes: MCF-7/Adr exosomes (A/exo and MCF-7/Doc exosomes (D/exo. The PTEN expression affected by β-elemene was significantly increased, and the Pgp expression affected by β-elemene was significantly decreased in both cells and exosomes. β-elemene induced a significant increase in the apoptosis rate in both MCF-7/Doc and MCF-7

  15. Establishing Substantial Equivalence: Transcriptomics

    Science.gov (United States)

    Baudo, María Marcela; Powers, Stephen J.; Mitchell, Rowan A. C.; Shewry, Peter R.

    Regulatory authorities in Western Europe require transgenic crops to be substantially equivalent to conventionally bred forms if they are to be approved for commercial production. One way to establish substantial equivalence is to compare the transcript profiles of developing grain and other tissues of transgenic and conventionally bred lines, in order to identify any unintended effects of the transformation process. We present detailed protocols for transcriptomic comparisons of developing wheat grain and leaf material, and illustrate their use by reference to our own studies of lines transformed to express additional gluten protein genes controlled by their own endosperm-specific promoters. The results show that the transgenes present in these lines (which included those encoding marker genes) did not have any significant unpredicted effects on the expression of endogenous genes and that the transgenic plants were therefore substantially equivalent to the corresponding parental lines.

  16. Lipid Replacement Therapy: a Functional Food Approach with New Formulations for Reducing Cellular Oxidative Damage, Cancer-Associated Fatigue and the Adverse Effects of Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Garth L. Nicolson

    2011-04-01

    Full Text Available Backgroud:Cancer-associated fatigue and the chronic adverse effects of cancer therapy can be reduced by Lipid Replacement Therapy (LRT using membrane phospholipid mixtures given as food supplements.Methods:This is a review of the published literature on LRT and its uses.Results: LRT significantly reduced fatigue in cancer patients as well as patients suffering from chronic fatiguing illnesses and other medical conditions. It also reduced the adverse effects of chemotherapy, resulting in improvements in incidence of fatigue, nausea, diarrhea, impaired taste, constipation, insomnia and other quality of life indicators. In other diseases, such as chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses, LRT reduced fatigue by 35.5-43.1% in different clinical trials and increased mitochondrial function.Conclusions: LRT formulations appear to be useful as non-toxic dietary supplements for direct use or placed in functional foods to reduce fatigue and restore mitochondrial and other cellular membrane functions. Formulations of LRT phospholipids are suitable for addition to variousfood products for the treatment of a variety of chronic illnesses as well as their application inanti-aging and other health supplements and products.

  17. Developmental transcriptome of Aplysia californica'

    KAUST Repository

    Heyland, Andreas; Vue, Zer; Voolstra, Christian R.; Medina, Mó nica; Moroz, Leonid L.

    2010-01-01

    developmental transcriptome with similar studies in the zebra fish Danio rerio, the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, and other studies on molluscs suggests an overall highly divergent pattern of gene regulatory mechanisms

  18. Transcriptomic profiling of curcumin-treated human breast stem cells identifies a role for stearoyl-coa desaturase in breast cancer prevention.

    Science.gov (United States)

    Colacino, Justin A; McDermott, Sean P; Sartor, Maureen A; Wicha, Max S; Rozek, Laura S

    2016-07-01

    Curcumin is a potential agent for both the prevention and treatment of cancers. Curcumin treatment alone, or in combination with piperine, limits breast stem cell self-renewal, while remaining non-toxic to normal differentiated cells. We paired fluorescence-activated cell sorting with RNA sequencing to characterize the genome-wide changes induced specifically in normal breast stem cells following treatment with these compounds. We generated genome-wide maps of the transcriptional changes that occur in epithelial-like (ALDH+) and mesenchymal-like (ALDH-/CD44+/CD24-) normal breast stem/progenitor cells following treatment with curcumin and piperine. We show that curcumin targets both stem cell populations by down-regulating expression of breast stem cell genes including ALDH1A3, CD49f, PROM1, and TP63. We also identified novel genes and pathways targeted by curcumin, including downregulation of SCD. Transient siRNA knockdown of SCD in MCF10A cells significantly inhibited mammosphere formation and the mean proportion of CD44+/CD24- cells, suggesting that SCD is a regulator of breast stemness and a target of curcumin in breast stem cells. These findings extend previous reports of curcumin targeting stem cells, here in two phenotypically distinct stem/progenitor populations isolated from normal human breast tissue. We identified novel mechanisms by which curcumin and piperine target breast stem cell self-renewal, such as by targeting lipid metabolism, providing a mechanistic link between curcumin treatment and stem cell self-renewal. These results elucidate the mechanisms by which curcumin may act as a cancer-preventive compound and provide novel targets for cancer prevention and treatment.

  19. Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden

    International Nuclear Information System (INIS)

    Abubaker, Khalid; Luwor, Rodney B; Zhu, Hongjian; McNally, Orla; Quinn, Michael A; Burns, Christopher J; Thompson, Erik W; Findlay, Jock K; Ahmed, Nuzhat

    2014-01-01

    Current treatment of ovarian cancer patients with chemotherapy leaves behind a residual tumor which results in recurrent ovarian cancer within a short time frame. We have previously demonstrated that a single short-term treatment of ovarian cancer cells with chemotherapy in vitro resulted in a cancer stem cell (CSC)-like enriched residual population which generated significantly greater tumor burden compared to the tumor burden generated by control untreated cells. In this report we looked at the mechanisms of the enrichment of CSC-like residual cells in response to paclitaxel treatment. The mechanism of survival of paclitaxel-treated residual cells at a growth inhibitory concentration of 50% (GI50) was determined on isolated tumor cells from the ascites of recurrent ovarian cancer patients and HEY ovarian cancer cell line by in vitro assays and in a mouse xenograft model. Treatment of isolated tumor cells from the ascites of ovarian cancer patients and HEY ovarian cancer cell line with paclitaxel resulted in a CSC-like residual population which coincided with the activation of Janus activated kinase 2 (JAK2) and signal transducer and activation of transcription 3 (STAT3) pathway in paclitaxel surviving cells. Both paclitaxel-induced JAK2/STAT3 activation and CSC-like characteristics were inhibited by a low dose JAK2-specific small molecule inhibitor CYT387 (1 μM) in vitro. Subsequent, in vivo transplantation of paclitaxel and CYT387-treated HEY cells in mice resulted in a significantly reduced tumor burden compared to that seen with paclitaxel only-treated transplanted cells. In vitro analysis of tumor xenografts at protein and mRNA levels demonstrated a loss of CSC-like markers and CA125 expression in paclitaxel and CYT387-treated cell-derived xenografts, compared to paclitaxel only-treated cell-derived xenografts. These results were consistent with significantly reduced activation of JAK2 and STAT3 in paclitaxel and CYT387-treated cell-derived xenografts

  20. Adenovirus-Mediated Delivery of Decoy Hyper Binding Sites Targeting Oncogenic HMGA1 Reduces Pancreatic and Liver Cancer Cell Viability.

    Science.gov (United States)

    Hassan, Faizule; Ni, Shuisong; Arnett, Tyler C; McKell, Melanie C; Kennedy, Michael A

    2018-03-30

    High mobility group AT-hook 1 (HMGA1) protein is an oncogenic architectural transcription factor that plays an essential role in early development, but it is also implicated in many human cancers. Elevated levels of HMGA1 in cancer cells cause misregulation of gene expression and are associated with increased cancer cell proliferation and increased chemotherapy resistance. We have devised a strategy of using engineered viruses to deliver decoy hyper binding sites for HMGA1 to the nucleus of cancer cells with the goal of sequestering excess HMGA1 at the decoy hyper binding sites due to binding competition. Sequestration of excess HMGA1 at the decoy binding sites is intended to reduce HMGA1 binding at the naturally occurring genomic HMGA1 binding sites, which should result in normalized gene expression and restored sensitivity to chemotherapy. As proof of principle, we engineered the replication defective adenovirus serotype 5 genome to contain hyper binding sites for HMGA1 composed of six copies of an individual HMGA1 binding site, referred to as HMGA-6. A 70%-80% reduction in cell viability and increased sensitivity to gemcitabine was observed in five different pancreatic and liver cancer cell lines 72 hr after infection with replication defective engineered adenovirus serotype 5 virus containing the HMGA-6 decoy hyper binding sites. The decoy hyper binding site strategy should be general for targeting overexpression of any double-stranded DNA-binding oncogenic transcription factor responsible for cancer cell proliferation.

  1. Cymbopogon citratus and Camellia sinensis extracts selectively induce apoptosis in cancer cells and reduce growth of lymphoma xenografts in vivo

    Science.gov (United States)

    Philion, Cory; Ma, Dennis; Ruvinov, Ivan; Mansour, Fadi; Pignanelli, Christopher; Noel, Megan; Saleem, Ammar; Arnason, John; Rodrigues, Mark; Singh, Inderpal; Ropat, Jesse; Pandey, Siyaram

    2017-01-01

    Cancer cells are reported to have elevated levels of reactive oxygen species (ROS) and are highly dependent on cellular defense mechanisms against oxidative stress. Numerous nutraceuticals and natural polyphenolic compounds have a wide range of abilities to alter cellular redox states with potential implications in various diseases. Furthermore, therapeutic options for cancers are mostly nonselective treatments including genotoxic or tubulin-targeting compounds. Some of the natural extracts, containing multiple bioactive compounds, could target multiple pathways in cancer cells to selectively induce cell death. Cymbopogon citratus (lemongrass) and Camellia sinensis (white tea) extracts have been shown to have medicinal properties, however, their activity against lymphoma and leukemia, as well as mechanistic details, have not been fully characterized. Herein, we report potent anti-cancer properties in dose and time-dependent manners of ethanolic lemongrass and hot water white tea extracts in lymphoma and leukemia models. Both extracts were able to effectively induce apoptosis selectively in these human cancer cell types. Interestingly, ethanolic lemongrass extract induces apoptosis primarily by the extrinsic pathway and was found to be dependent on the generation of ROS. Conversely, apoptotic induction by hot water white tea extract was independent of ROS. Furthermore, both of these extracts caused mitochondrial depolarization and decreased rates of oxygen consumption in lymphoma and leukemia cells, leading to cell death. Most importantly, both these extracts were effective in reducing tumor growth in human lymphoma xenograft models when administered orally. Thus, these natural extracts could have potential for being nontoxic alternatives for the treatment of cancer. PMID:29340014

  2. Transcriptomic dissection of tongue squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Schwartz Joel L

    2008-02-01

    Full Text Available Abstract Background The head and neck/oral squamous cell carcinoma (HNOSCC is a diverse group of cancers, which develop from many different anatomic sites and are associated with different risk factors and genetic characteristics. The oral tongue squamous cell carcinoma (OTSCC is one of the most common types of HNOSCC. It is significantly more aggressive than other forms of HNOSCC, in terms of local invasion and spread. In this study, we aim to identify specific transcriptomic signatures that associated with OTSCC. Results Genome-wide transcriptomic profiles were obtained for 53 primary OTSCCs and 22 matching normal tissues. Genes that exhibit statistically significant differences in expression between OTSCCs and normal were identified. These include up-regulated genes (MMP1, MMP10, MMP3, MMP12, PTHLH, INHBA, LAMC2, IL8, KRT17, COL1A2, IFI6, ISG15, PLAU, GREM1, MMP9, IFI44, CXCL1, and down-regulated genes (KRT4, MAL, CRNN, SCEL, CRISP3, SPINK5, CLCA4, ADH1B, P11, TGM3, RHCG, PPP1R3C, CEACAM7, HPGD, CFD, ABCA8, CLU, CYP3A5. The expressional difference of IL8 and MMP9 were further validated by real-time quantitative RT-PCR and immunohistochemistry. The Gene Ontology analysis suggested a number of altered biological processes in OTSCCs, including enhancements in phosphate transport, collagen catabolism, I-kappaB kinase/NF-kappaB signaling cascade, extracellular matrix organization and biogenesis, chemotaxis, as well as suppressions of superoxide release, hydrogen peroxide metabolism, cellular response to hydrogen peroxide, keratinization, and keratinocyte differentiation in OTSCCs. Conclusion In summary, our study provided a transcriptomic signature for OTSCC that may lead to a diagnosis or screen tool and provide the foundation for further functional validation of these specific candidate genes for OTSCC.

  3. The Clinical Effects of Aromatherapy Massage on Reducing Pain for the Cancer Patients: Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Ting-Hao Chen

    2016-01-01

    Full Text Available Purpose. Aromatherapy massage is an alternative treatment in reducing the pain of the cancer patients. This study was to investigate whether aromatherapy massage could improve the pain of the cancer patients. Methods. We searched PubMed and Cochrane Library for relevant randomized controlled trials without language limitations between 1 January 1990 and 31 July 2015 with a priori defined inclusion and exclusion criteria. The search terms included aromatherapy, essential oil, pain, ache, cancer, tumor, and carcinoma. There were 7 studies which met the selection criteria and 3 studies were eventually included among 63 eligible publications. Results. This meta-analysis included three randomized controlled trials with a total of 278 participants (135 participants in the massage with essential oil group and 143 participants in the control (usual care group. Compared with the control group, the massage with essential oil group had nonsignificant effect on reducing the pain (standardized mean difference = 0.01; 95% CI [-0.23,0.24]. Conclusion. Aromatherapy massage does not appear to reduce pain of the cancer patients. Further rigorous studies should be conducted with more objective measures.

  4. Breast Cancer Risk-reducing Strategies in BRCA1/2 Mutation Carriers

    NARCIS (Netherlands)

    B.A.M. Heemskerk-Gerritsen (Bernadette)

    2014-01-01

    textabstract__Abstract__ Breast cancer (BC) is the most common type of cancer in women in developed countries. Currently, approximately 14,000 women are diagnosed with BC every year in the Netherlands. One out of eight Dutch women (12%-13%) will develop BC during their life, and 3% to 4% of

  5. Cetuximab Reduces the Accumulation of Radiolabeled Bevacizumab in Cancer Xenografts without Decreasing VEGF Expression

    NARCIS (Netherlands)

    Heskamp, Sandra; Boerman, Otto C.; Molkenboer-Kuenen, Janneke D. M.; Sweep, Fred C. G. J.; Geurts-Moespot, Anneke; Engelhardt, Mallory S.; van der Graaf, Winette T. A.; Oyen, Wim J. G.; van Laarhoven, Hanneke W. M.

    2014-01-01

    Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains unclear. The aim of this study was to determine the effect of

  6. Cetuximab reduces the accumulation of radiolabeled bevacizumab in cancer xenografts without altering VEGF expression

    NARCIS (Netherlands)

    Heskamp, S.; Boerman, O.C.; Molkenboer-Kuenen, J.D.M.; Sweep, F.C.; Geurts-Moespot, A.; Engelhardt, M.S.; Graaf, W.T.A. van der; Oyen, W.J.G.; Laarhoven, H.W.M. van

    2014-01-01

    Introduction: Bevacizumab and cetuximab are approved for the treatment of cancer. However, in advanced colorectal cancer, addition of cetuximab to chemotherapy with bevacizumab did not improve survival. The reason for the lack of activity remains unclear. The aim of this study was to determine the

  7. Reduced delay in diagnosis of cancer after implementation of ‘fast track’

    DEFF Research Database (Denmark)

    Jensen, Henry; Tørring, Marie Louise; Vedsted, Peter

    In Denmark, the National Integrated Cancer Pathways (“fast track”) was introduced in 2008 as a response to the long waiting times. We performed a natural experiment of 14,023 cancer patients to compare the length of time intervals before and after the introduction of “fast-track”. We saw a decrea...

  8. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    DEFF Research Database (Denmark)

    Longo Martins, Murillo; Ignazzi, Rosanna; Eckert, Juergen

    2016-01-01

    -cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms...... design is potentially safer to healthy cells....

  9. Active surveillance can reduce overtreatment in patients with low-risk prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik Birkebæk; Røder, Martin Andreas; Hvarness, Helle

    2013-01-01

    The incidence of prostate cancer in Denmark rose approximately 50% from 2000 to 2009 in parallel with the introduction of prostate-specific antigen (PSA)-testing. Available evidence indicates a significant overtreatment of patients with low-risk prostate cancer. Active surveillance has been...

  10. Religion and Reduced Cancer Risk – What Is the Explanation? A Review

    DEFF Research Database (Denmark)

    Johannessen-Henry, Christine Tind

    2008-01-01

    was also made for healthy habits, no reduction in risk for cancer was observed. We conclude that the most important factor in the correlation between membership in a religious Christian community and risk for cancer is the healthy lifestyle inherent in religious practice in these communities...

  11. Fast track diagnosis as a means of reducing diagnostic delay in cancer

    DEFF Research Database (Denmark)

    Larsen, Mette Bach; Vedsted, Peter; Olesen, Frede

    of cancer and expanded services to the general practitioners. Objective: To investigate the diagnostic delay of cancer, patient and provider satisfaction and health economic aspects in two Danish regions with special emphasis on the possible benefits of fast track diagnosis. Methods: The study......Background: Denmark has the highest morbidity and mortality from cancer in Western Europe, and studies suggest that Danish cancer patients are diagnosed at a later stage than patients in the other Nordic countries. To address this issue a Danish hospital has introduced fast track diagnosis...... will be designed as a cross-sectional study with the construction of a clinical database of all incident cancers in two Danish regions within a year (12,000 patients). Data will be collected from general practitioners, patients and national registers. In the first part of the analysis the general variation...

  12. A new approach to reduce uncertainties in space radiation cancer risk predictions.

    Directory of Open Access Journals (Sweden)

    Francis A Cucinotta

    Full Text Available The prediction of space radiation induced cancer risk carries large uncertainties with two of the largest uncertainties being radiation quality and dose-rate effects. In risk models the ratio of the quality factor (QF to the dose and dose-rate reduction effectiveness factor (DDREF parameter is used to scale organ doses for cosmic ray proton and high charge and energy (HZE particles to a hazard rate for γ-rays derived from human epidemiology data. In previous work, particle track structure concepts were used to formulate a space radiation QF function that is dependent on particle charge number Z, and kinetic energy per atomic mass unit, E. QF uncertainties where represented by subjective probability distribution functions (PDF for the three QF parameters that described its maximum value and shape parameters for Z and E dependences. Here I report on an analysis of a maximum QF parameter and its uncertainty using mouse tumor induction data. Because experimental data for risks at low doses of γ-rays are highly uncertain which impacts estimates of maximum values of relative biological effectiveness (RBEmax, I developed an alternate QF model, denoted QFγAcute where QFs are defined relative to higher acute γ-ray doses (0.5 to 3 Gy. The alternate model reduces the dependence of risk projections on the DDREF, however a DDREF is still needed for risk estimates for high-energy protons and other primary or secondary sparsely ionizing space radiation components. Risk projections (upper confidence levels (CL for space missions show a reduction of about 40% (CL∼50% using the QFγAcute model compared the QFs based on RBEmax and about 25% (CL∼35% compared to previous estimates. In addition, I discuss how a possible qualitative difference leading to increased tumor lethality for HZE particles compared to low LET radiation and background tumors remains a large uncertainty in risk estimates.

  13. Reduced recurrence of late hemorrhagic radiation cystitis by WF10 therapy in cervical cancer patients

    International Nuclear Information System (INIS)

    Veerasarn, Vutisiri; Khorprasert, Chonlakiet; Lorvidhaya, Vicharn; Sangruchi, Supatra; Tantivatana, Thanatip; Narkwong, Ladawan; Kongthanarat, Yongyut; Chitapanarux, Imjai; Tesavibul, Chanawat; Panichevaluk, Apichart; Puribhat, Sirisak; Sangkittipaiboon, Somphob; Sookpreedee, Lak; Lertsanguansinchai, Prasert; Phromratanapongse, Pramook; Rungpoka, Poonkiat; Trithratipvikul, Supamitr; Lojanapiwat, Bannakij; Ruangdilokrat, Sathit; Ngampanprasert, Pichai

    2004-01-01

    Background and purpose: To evaluate the efficacy and the safety of WF10 as adjunct to standard treatment in the management of late hemorrhagic radiation cystitis compared to standard treatment alone. Patients and methods: Cervical cancer patients with Grade 2 or 3 late hemorrhagic radiation cystitis, were randomized and treated with WF10 0.5 ml/kg body weight, diluted in physiological saline or 5% dextrose water 250 ml, intravenous infusions over 2 h on 5 consecutive days, every 3 weeks for 2 cycles plus standard treatment (WF10 group) or standard treatment alone (control group). Fifty patients in each group were evaluated by questioning; urinalysis and cystoscopy during a 1 year follow up. Results: At week 7, 37 patients (74%) in the WF10 group and 32 patients (64%) in the control group showed complete resolution in objective hematuria (P=0.28). Significantly lower use of antibiotics (P=0.002) and antispasmodics (P<0.001) was found in the WF10 group. Among the responders, 24 patients (77%) in the control group experienced recurrent objective hematuria, whereas in the WF10 group only 17 patients (47%) experienced a recurrence (P=0.01). Recurrence of objective hematuria occurred significantly faster in the control group as evidenced by Kaplan-Meier and log-rank statistics (P=0.004), suggesting a long-term effect of WF10. Cystoscopy, at the end of the treatment period and after the one year follow up showed overall improvement without significant difference between two groups. No severe toxicity was monitored. Conclusions: WF10 therapy is a safe, non-invasive and convenient method in the management of late hemorrhagic radiation cystitis. WF10 therapy, as adjunct to standard treatment, has significantly reduced recurrence of objective hematuria, compared to standard treatment alone, during a one year follow up

  14. Association Between Coffee Intake After Diagnosis of Colorectal Cancer and Reduced Mortality.

    Science.gov (United States)

    Hu, Yang; Ding, Ming; Yuan, Chen; Wu, Kana; Smith-Warner, Stephanie A; Hu, Frank B; Chan, Andrew T; Meyerhardt, Jeffrey A; Ogino, Shuji; Fuchs, Charles S; Giovannucci, Edward L; Song, Mingyang

    2018-03-01

    Few studies have examined the association between coffee intake and survival after diagnosis of colorectal cancer (CRC). We performed a prospective study to investigate the association between coffee intake after a diagnosis of CRC and mortality. We collected data from the Nurses' Health Study (1984-2012) and Health Professionals Follow-up Study (1986-2012), following 1599 patients diagnosed with stage 1, 2, or 3 CRC. CRC was reported on questionnaires and ascertained by review of medical records and pathology reports; intake of food and beverages was determined from responses to semi-quantitative food frequency questionnaires. Participants were asked how often during the previous year that they consumed coffee, with 1 cup as the standard portion size. The first questionnaire response collected at least 6 months but not more than 4 years after diagnosis was used for assessment of post-diagnostic intake (median time from diagnosis to the dietary assessment, 2.2 years). The last semi-quantitative food frequency questionnaire prior to diagnosis was used to assess pre-diagnostic dietary intake. During a median of 7.8 years of follow-up, we documented 803 deaths, of which 188 were because of CRC. In the multivariable adjusted models, compared with nondrinkers, patients who consumed at least 4 cups of coffee per day had a 52% lower risk of CRC-specific death (hazard ratio [HR] 0.48; 95% CI, 0.28-0.83; P for trend=.003) and 30% reduced risk of all-cause death (HR, 0.70; 95% CI, 0.54-0.91; P for trend coffee (2 or more cups/day) was associated with lower risk of CRC-specific mortality and all-cause mortality. When coffee intake before vs after CRC diagnosis were examined, compared with patients consistently consuming low amounts (less than 2 cups/day), those who maintained a high intake (2 or more cups/day) had a significantly lower risk of CRC-specific death (multivariable HR, 0.63; 95% CI, 0.44-0.89) and death from any cause (multivariable HR, 0.71; 95% CI, 0

  15. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

    Science.gov (United States)

    ZHAO, BING; HU, MENGCAI

    2013-01-01

    Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer. PMID:24843386

  16. Leveraging iPads to introduce meditation and reduce distress among cancer patients undergoing chemotherapy: a promising approach.

    Science.gov (United States)

    Millegan, Jeffrey; Manschot, Bernard; Dispenzieri, Monica; Marks, Benjamin; Edwards, Ayesha; Raulston, Vanessa; Khatiwoda, Yojana; Narro, Marlo

    2015-12-01

    Distress is common among cancer patients. Regular meditation practice has the potential to mitigate this distress and improve quality of life for this population. Introducing meditation to cancer patients can be particularly challenging given the demands on patients' time from treatment and normal life events. This internal process improvement study examined the potential benefit of utilizing iPads during chemotherapy sessions to introduce meditation and reduce distress. Patients undergoing chemotherapy infusion were offered iPads with various meditation videos and audio files during the session. Levels of distress were measured using the distress thermometer at the beginning of chemotherapy and at the conclusion of chemotherapy. Seventy-three patients accepted the meditation iPads during the chemotherapy session. Among those who accepted the iPads, average distress dropped 46% by the end of the session (p meditation as a stress management tool for people with cancer.

  17. Observational methods to assess the effectiveness of screening colonoscopy in reducing right colon cancer mortality risk: SCOLAR.

    Science.gov (United States)

    Goodman, Michael; Fletcher, Robert H; Doria-Rose, V Paul; Jensen, Christopher D; Zebrowski, Alexis M; Becerra, Tracy A; Quinn, Virginia P; Zauber, Ann G; Corley, Douglas A; Doubeni, Chyke A

    2015-11-01

    Screening colonoscopy's effectiveness in reducing risk of death from right colon cancers remains unclear. Methodological challenges of existing observational studies addressing this issue motivated the design of 'Effectiveness of Screening for Colorectal Cancer in Average-Risk Adults (SCOLAR)'. SCOLAR is a nested case-control study based on two large integrated health systems. This affords access to a large, well-defined historical cohort linked to integrated data on cancer outcomes, patient eligibility, test indications and important confounders. We found electronic data adequate for excluding ineligible patients (except family history), but not the detailed information needed for test indication assignment. The lessons of SCOLAR's design and implementation may be useful for future studies seeking to evaluate the effectiveness of screening tests in community settings.

  18. Avoiding the ingestion of cytotoxic concentrations of ethanol may reduce the risk of cancer associated with alcohol consumption.

    Science.gov (United States)

    Guillén-Mancina, Emilio; Calderón-Montaño, José Manuel; López-Lázaro, Miguel

    2018-02-01

    Alcohol consumption is a known risk factor for cancer. Almost 6% of all cancers worldwide are attributable to alcohol use. Approximately half of them occur in tissues highly exposed to ethanol, such as the oral cavity, pharynx, upper larynx and esophagus. However, since ethanol is not mutagenic and the mutagenic metabolite of ethanol (acetaldehyde) is mainly produced in the liver, it is unclear why alcohol consumption preferentially exerts a local carcinogenic effect. Recent findings indicate that the risk of cancer in a tissue is strongly correlated with the number of stem cell divisions accumulated by the tissue; the accumulation of stem cell divisions leads to the accumulation of cancer-promoting errors such as mutations occurring during DNA replication. Since cell death activates the division of stem cells, we recently proposed that the possible cytotoxicity of ethanol on the cells lining the tissues in direct contact with alcoholic beverages could explain the local carcinogenic effect of alcohol. Here we report that short-term exposures (2-3 s) to ethanol concentrations between 10% and 15% start to cause a marked cytotoxic effect on human epithelial keratinocytes in a concentration-dependent manner. We propose that choosing alcoholic beverages containing non-cytotoxic concentrations of ethanol, or diluting ethanol to non-cytotoxic concentrations, may be a simple and effective way to reduce the risk of cancers of the oral cavity, pharynx, larynx and esophagus in alcohol users. This preventive strategy may also reduce the known synergistic effect of alcohol drinking and tobacco smoking on the risk of these cancers. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Reduced-port robotic total mesorectal resection for rectal cancer using a single-port access: a technical note.

    Science.gov (United States)

    Bae, Sung Uk; Jeong, Woon Kyung; Baek, Seong Kyu

    2017-12-01

    Single-port laparoscopic surgery has some advantages, including improved cosmetic outcomes and minimized parietal trauma. However, pure single-port laparoscopic rectal cancer surgery is challenging because of the difficulties in creating triangulation and applying the laparoscopic staplers with sufficient distal margins in the narrow pelvic cavity. Recently, a reduced-port robotic operation with a robotic single-port access plus one wristed robotic arm for colon cancer was introduced to overcome the limitations of single-port laparoscopic rectal surgery. Single-port laparoscopic surgery has some advantages, including improved cosmetic outcomes and minimized parietal trauma. However, the pure single-port laparoscopic rectal cancer operation is challenging. Recently, a reduced-port robotic operation with a robotic single-port access plus one wristed robotic arm for colon cancer was introduced to overcome the limitations of single-port laparoscopic rectal surgery. We performed a single-port plus an additional port robotic operation using a robotic single-port access through the umbilical incision, and the wristed robotic instruments were inserted through an additional robotic port in the right lower quadrant. The total operative and docking times were 310 min and 25 min, respectively. The total number of lymph nodes harvested was 12, and the proximal and distal resection margins were 11.1 and 2 cm, respectively. The patient was discharged on postoperative day 12 uneventfully. Based on a representative case, reduced-port robotic total mesorectal excision for rectal cancer using the single-port access appears to be feasible and safe. This approach could overcome the limitations of single-port laparoscopic rectal surgery.

  20. Massage Therapy for Reducing Stress Hormones and Enhancing Immune Function in Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Ironson, Gail

    2001-01-01

    The objectives and specific aims of the ongoing study are to evaluate massage and relaxation therapies for an ethnically diverse group of women with early stages of breast cancer (Stages 1 and 2) for 1...

  1. Massage Therapy for Reducing Stress Hormones and Enhancing Immune Function in Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Tronson, Gail

    2000-01-01

    The objectives and specific aims of the ongoing study are to evaluate massage and relaxation therapies for an ethnically diverse group of women with early stages of breast cancer (Stages 1 and 2) for (1...

  2. Intrathoracic Anastomotic Leakage after Gastroesophageal Cancer Resection Is Associated with Reduced Long-term Survival

    DEFF Research Database (Denmark)

    Kofoed, Steen Christian; Calatayud, Dan; Jensen, Lone Susanne

    2014-01-01

    BACKGROUND: Most likely because of low statistical power, no previous studies have shown any significant association between long-term survival and anastomotic leakage in patients who have undergone gastroesophageal cancer resection. MATERIAL AND METHODS: The present study included, prospectively...

  3. Gastric Cancer: How Can We Reduce the Incidence of this Disease?

    NARCIS (Netherlands)

    C.M. den Hoed (Caroline); E.J. Kuipers (Ernst)

    2016-01-01

    textabstractGastric cancer remains a prevalent disease worldwide with a poor prognosis. Helicobacter pylori plays a major role in gastric carcinogenesis. H. pylori colonization leads to chronic gastritis, which predisposes to atrophic gastritis, intestinal metaplasia, dysplasia, and eventually

  4. Reduced Circumferential Resection Margin Involvement in Rectal Cancer Surgery: Results of the Dutch Surgical Colorectal Audit

    NARCIS (Netherlands)

    Gietelink, Lieke; Wouters, Michel W. J. M.; Tanis, Pieter J.; Deken, Marion M.; ten Berge, Martijn G.; Tollenaar, Rob A. E. M.; van Krieken, J. Han; de Noo, Mirre E.

    2015-01-01

    Background: The circumferential resection margin (CRM) is a significant prognostic factor for local recurrence, distant metastasis, and survival after rectal cancer surgery. Therefore, availability of this parameter is essential. Although the Dutch total mesorectal excision trial raised awareness

  5. Reduced Circumferential Resection Margin Involvement in Rectal Cancer Surgery: Results of the Dutch Surgical Colorectal Audit

    NARCIS (Netherlands)

    Gietelink, L.; Wouters, M.W.; Tanis, P.J.; Deken, M.M.; Berge, M.G. Ten; Tollenaar, R.A.; Krieken, J.H.J.M. van; Noo, M.E. de

    2015-01-01

    BACKGROUND: The circumferential resection margin (CRM) is a significant prognostic factor for local recurrence, distant metastasis, and survival after rectal cancer surgery. Therefore, availability of this parameter is essential. Although the Dutch total mesorectal excision trial raised awareness

  6. Massage Therapy for Reducing Stress Hormones and Enhancing Immune Function in Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Ironson, Gail

    2001-01-01

    ... (immune measures that fight tumors and viruses). During the course of the three-year study, 60 women diagnosed with Stage 1 and 2 breast cancer will be recruited and assigned to a massage therapy (n=20...

  7. Massage Therapy for Reducing Stress Hormones and Enhancing Immune Function in Breast Cancer Survivors

    National Research Council Canada - National Science Library

    Tronson, Gail

    2000-01-01

    ... (immune measures that fight tumors and viruses). During the course of the three-year study, 60 women diagnosed with Stage 1 and 2 breast cancer will be recruited and assigned to a massage therapy (n=20...

  8. Nurse-led group consultation intervention reduces depressive symptoms in men with localised prostate cancer: a cluster randomised controlled trial

    International Nuclear Information System (INIS)

    Schofield, Penelope; Gough, Karla; Lotfi-Jam, Kerryann; Bergin, Rebecca; Ugalde, Anna; Dudgeon, Paul; Crellin, Wallace; Schubach, Kathryn; Foroudi, Farshard; Tai, Keen Hun; Duchesne, Gillian; Sanson-Fisher, Rob; Aranda, Sanchia

    2016-01-01

    Radiotherapy for localised prostate cancer has many known and distressing side effects. The efficacy of group interventions for reducing psychological morbidity is lacking. This study investigated the relative benefits of a group nurse-led intervention on psychological morbidity, unmet needs, treatment-related concerns and prostate cancer-specific quality of life in men receiving curative intent radiotherapy for prostate cancer. This phase III, two-arm cluster randomised controlled trial included 331 men (consent rate: 72 %; attrition: 5 %) randomised to the intervention (n = 166) or usual care (n = 165). The intervention comprised four group and one individual consultation all delivered by specialist uro-oncology nurses. Primary outcomes were anxious and depressive symptoms as assessed by the Hospital Anxiety and Depression Scale. Unmet needs were assessed with the Supportive Care Needs Survey-SF34 Revised, treatment-related concerns with the Cancer Treatment Scale and quality of life with the Expanded Prostate Cancer Index −26. Assessments occurred before, at the end of and 6 months post-radiotherapy. Primary outcome analysis was by intention-to-treat and performed by fitting a linear mixed model to each outcome separately using all observed data. Mixed models analysis indicated that group consultations had a significant beneficial effect on one of two primary endpoints, depressive symptoms (p = 0.009), and one of twelve secondary endpoints, procedural concerns related to cancer treatment (p = 0.049). Group consultations did not have a significant beneficial effect on generalised anxiety, unmet needs and prostate cancer-specific quality of life. Compared with individual consultations offered as part of usual care, the intervention provides a means of delivering patient education and is associated with modest reductions in depressive symptoms and procedural concerns. Future work should seek to confirm the clinical feasibility and cost-effectiveness of group

  9. Factors Associated with Breast Cancer Screening in a Country with National Health Insurance: Did We Succeed in Reducing Healthcare Disparities?

    Science.gov (United States)

    Hayek, Samah; Enav, Teena; Shohat, Tamy; Keinan-Boker, Lital

    2017-02-01

    The effectiveness of breast cancer screening programs in reducing mortality is well established in the scientific literature. The National Breast Cancer Screening Program in Israel provides biennial mammograms for women of average risk aged 50-74 and annual mammograms for women aged 40-49 at higher risk. Compliance is high, but differential. This study explores different factors associated with breast cancer screening attendance among women aged 40-74 years. Two main outcomes were studied: ever been screened and been screened in the 2 years preceding the study, using the cross-sectional Knowledge, Attitudes and Practices (KAP) Survey conducted in 2010-2012 among 2575 Israeli women aged 21+ years. The independent variables were sociodemographic characteristics, perceived health status, lifestyle habits, and healthcare fund membership. Bivariate and multivariable logistic regressions were conducted. Of the 943 participants aged 50-74, 87% had ever been screened and 74.8% had attended screening for breast cancer in the last 2 years. In multivariable models, Jewish compared to Arab women (adjusted prevalence ratio [APR] = 2.09, 95% confidence interval [CI]: 1.02-4.32), and unmarried compared to married women (APR = 2.9, 95% CI: 1.2-7.2), were more likely to have ever been screened. The only factor associated with breast cancer screening in the 2 years preceding the study was healthcare fund membership. In women aged 40-49 years, ethnicity was the only contributing factor associated with breast cancer screening, with higher screening rates in the 2 years preceding the study in Jewish versus Arab women (APR = 3.7, 95% CI: 1.52-9.3). Breast cancer screening attendance in Israel is high. However, significant differences are observed by membership of healthcare fund and by ethnicity, calling for better targeted outreach programs at this level.

  10. How do women at increased breast cancer risk perceive and decide between risks of cancer and risk-reducing treatments? A synthesis of qualitative research.

    Science.gov (United States)

    Fielden, Hannah G; Brown, Stephen L; Saini, Pooja; Beesley, Helen; Salmon, Peter

    2017-09-01

    Risk-reducing procedures can be offered to people at increased cancer risk, but many procedures can have iatrogenic effects. People therefore need to weigh risks associated with both cancer and the risk-reduction procedure in their decisions. By reviewing relevant literature on breast cancer (BC) risk reduction, we aimed to understand how women at relatively high risk of BC perceive their risk and how their risk perceptions influence their decisions about risk reduction. Synthesis of 15 qualitative studies obtained from systematic searches of SCOPUS, Web of Knowledge, PsychINFO, and Medline electronic databases (inception-June 2015). Women did not think about risk probabilistically. Instead, they allocated themselves to broad risk categories, typically influenced by their own or familial experiences of BC. In deciding about risk-reduction procedures, some women reported weighing the risks and benefits, but papers did not describe how they did so. For many women, however, an overriding wish to reduce intense worry about BC led them to choose aggressive risk-reducing procedures without such deliberation. Reasoning that categorisation is a fundamental aspect of risk perception, we argue that patients can be encouraged to develop more nuanced and accurate categorisations of their own risk through their interactions with clinicians. Empirically-based ethical reflection is required to determine whether and when it is appropriate to provide risk-reduction procedures to alleviate worry. © 2016 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.

  11. Transcriptome Profiling in Human Diseases: New Advances and Perspectives

    Directory of Open Access Journals (Sweden)

    Amelia Casamassimi

    2017-07-01

    Full Text Available In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level. RNA sequencing has also been employed in important projects, like ENCODE (Encyclopedia of the regulatory elements and TCGA (The Cancer Genome Atlas, to provide a snapshot of the transcriptome of dozens of cell lines and thousands of primary tumor specimens. Moreover, these studies have also paved the way to the development of data integration approaches in order to facilitate management and analysis of data and to identify novel disease markers and molecular targets to use in the clinics. In this scenario, several ongoing clinical trials utilize transcriptome profiling through RNA sequencing strategies as an important instrument in the diagnosis of numerous human pathologies.

  12. Transcriptome Profiling in Human Diseases: New Advances and Perspectives.

    Science.gov (United States)

    Casamassimi, Amelia; Federico, Antonio; Rienzo, Monica; Esposito, Sabrina; Ciccodicola, Alfredo

    2017-07-29

    In the last decades, transcriptome profiling has been one of the most utilized approaches to investigate human diseases at the molecular level. Through expression studies, many molecular biomarkers and therapeutic targets have been found for several human pathologies. This number is continuously increasing thanks to total RNA sequencing. Indeed, this new technology has completely revolutionized transcriptome analysis allowing the quantification of gene expression levels and allele-specific expression in a single experiment, as well as to identify novel genes, splice isoforms, fusion transcripts, and to investigate the world of non-coding RNA at an unprecedented level. RNA sequencing has also been employed in important projects, like ENCODE (Encyclopedia of the regulatory elements) and TCGA (The Cancer Genome Atlas), to provide a snapshot of the transcriptome of dozens of cell lines and thousands of primary tumor specimens. Moreover, these studies have also paved the way to the development of data integration approaches in order to facilitate management and analysis of data and to identify novel disease markers and molecular targets to use in the clinics. In this scenario, several ongoing clinical trials utilize transcriptome profiling through RNA sequencing strategies as an important instrument in the diagnosis of numerous human pathologies.

  13. Which strategies reduce breast cancer mortality most? Collaborative modeling of optimal screening, treatment, and obesity prevention.

    Science.gov (United States)

    Mandelblatt, Jeanne; van Ravesteyn, Nicolien; Schechter, Clyde; Chang, Yaojen; Huang, An-Tsun; Near, Aimee M; de Koning, Harry; Jemal, Ahmedin

    2013-07-15

    US breast cancer mortality is declining, but thousands of women still die each year. Two established simulation models examine 6 strategies that include increased screening and/or treatment or elimination of obesity versus continuation of current patterns. The models use common national data on incidence and obesity prevalence, competing causes of death, mammography characteristics, treatment effects, and survival/cure. Parameters are modified based on obesity (defined as BMI  ≥  30 kg/m(2) ). Outcomes are presented for the year 2025 among women aged 25+ and include numbers of cases, deaths, mammograms and false-positives; age-adjusted incidence and mortality; breast cancer mortality reduction and deaths averted; and probability of dying of breast cancer. If current patterns continue, the models project that there would be about 50,100-57,400 (range across models) annual breast cancer deaths in 2025. If 90% of women were screened annually from ages 40 to 54 and biennially from ages 55 to 99 (or death), then 5100-6100 fewer deaths would occur versus current patterns, but incidence, mammograms, and false-positives would increase. If all women received the indicated systemic treatment (with no screening change), then 11,400-14,500 more deaths would be averted versus current patterns, but increased toxicity could occur. If 100% received screening plus indicated therapy, there would be 18,100-20,400 fewer deaths. Eliminating obesity yields 3300-5700 fewer breast cancer deaths versus continuation of current obesity levels. Maximal reductions in breast cancer deaths could be achieved through optimizing treatment use, followed by increasing screening use and obesity prevention. © 2013 American Cancer Society.

  14. A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

    Directory of Open Access Journals (Sweden)

    Glen J Weiss

    Full Text Available Small cell lung cancer (SCLC that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients.Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50% received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration. The remaining patients had clinical deterioration before NGS recommended therapy could be initiated.Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.

  15. A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

    Science.gov (United States)

    Weiss, Glen J; Byron, Sara A; Aldrich, Jessica; Sangal, Ashish; Barilla, Heather; Kiefer, Jeffrey A; Carpten, John D; Craig, David W; Whitsett, Timothy G

    2017-01-01

    Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated. Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.

  16. Perioperative epidural analgesia reduces cancer recurrence after gastro-oesophageal surgery.

    Science.gov (United States)

    Hiller, J G; Hacking, M B; Link, E K; Wessels, K L; Riedel, B J

    2014-03-01

    Recent interest has focused on the role of perioperative epidural analgesia in improving cancer outcomes. The heterogeneity of studies (tumour type, stage and outcome endpoints) has produced inconsistent results. Clinical practice also highlights the variability in epidural effectiveness. We considered the novel hypothesis that effective epidural analgesia improves cancer outcomes following gastro-oesophageal cancer surgery in patients with grouped pathological staging. Following institutional approval, a database analysis identified 140 patients, with 2-year minimum follow-up after gastro-oesophageal cancer surgery. All patients were operated on by a single surgeon (2005-2010). Information pertaining to cancer and survival outcomes was extracted. Univariate analysis demonstrated a 1-year 14% vs. 33% (P = 0.01) and 2-year 27% vs. 40% [hazard ratio (HR)=0.59; 95% CI, 0.32-1.09, P = 0.087] incidence of cancer recurrence in patients with (vs. without) effective (> 36 h duration) epidural analgesia, respectively. Multivariate analysis demonstrated increased time to cancer recurrence (HR = 0.33; 95% CI: 0.17-0.63, P benefit (HR = 0.42; 95% CI: 0.21-0.83, P benefit in patients with oesophageal cancer (HR = 0.34; 95% CI: 0.16-0.75, P = 0.005) and in patients with tumour lymphovascular space infiltration (LVSI), (HR = 0.49; 95% CI: 0.26-0.94, P = 0.03). Effective epidural analgesia improved estimated median time to death (2.9 vs. 1.8 years, P = 0.029) in patients with tumour LVSI. This study found an association between effective post-operative epidural analgesia and medium-term benefit on cancer recurrence and survival following oesophageal surgery. A prospective study that controls for disease type, stage and epidural effectiveness is warranted. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  17. High intake of specific carotenoids and flavonoids does not reduce the risk of bladder cancer.

    Science.gov (United States)

    Garcia, R; Gonzalez, C A; Agudo, A; Riboli, E

    1999-01-01

    An analysis of a previously completed Spanish multicentric case-control study of bladder cancer was carried out using new available data on the contents in foods of specific carotenoids (alpha-carotene, beta-carotene, lutein, and lycopene) and flavonoids (quercetin, kaempferol, myricetin, and luteolin) to investigate the relationship of these phytochemicals with bladder cancer. The study included 497 cases first diagnosed with bladder cancer, 547 neighborhood controls, and 566 hospitals controls, matched by gender, age, area of residence, and hospital. Usual food intake was estimated using a dietary history questionnaire administered by trained interviewers. None of the specific carotenoids and none of the specific flavonoids have been found to be significantly associated with bladder cancer risk in this analysis. The adjusted odds ratios for subjects in the highest quartile of intake with respect to subjects in the lowest quartile were 1.36 (95% confidence interval = 0.94-1.95) for total carotenoid intake and 1.23 (95% confidence interval = 0.85-1.79) for total flavonoid intake. The results of this study does not support the hypothesis that intake of specific carotenoids and flavonoids is protective against bladder cancer risk.

  18. RNA-Based TWIST1 Inhibition via Dendrimer Complex to Reduce Breast Cancer Cell Metastasis

    Directory of Open Access Journals (Sweden)

    James Finlay

    2015-01-01

    Full Text Available Breast cancer is the leading cause of cancer-related deaths among women in the United States, and survival rates are lower for patients with metastases and/or triple-negative breast cancer (TNBC; ER, PR, and Her2 negative. Understanding the mechanisms of cancer metastasis is therefore crucial to identify new therapeutic targets and develop novel treatments to improve patient outcomes. A potential target is the TWIST1 transcription factor, which is often overexpressed in aggressive breast cancers and is a master regulator of cellular migration through epithelial-mesenchymal transition (EMT. Here, we demonstrate an siRNA-based TWIST1 silencing approach with delivery using a modified poly(amidoamine (PAMAM dendrimer. Our results demonstrate that SUM1315 TNBC cells efficiently take up PAMAM-siRNA complexes, leading to significant knockdown of TWIST1 and EMT-related target genes. Knockdown lasts up to one week after transfection and leads to a reduction in migration and invasion, as determined by wound healing and transwell assays. Furthermore, we demonstrate that PAMAM dendrimers can deliver siRNA to xenograft orthotopic tumors and siRNA remains in the tumor for at least four hours after treatment. These results suggest that further development of dendrimer-based delivery of siRNA for TWIST1 silencing may lead to a valuable adjunctive therapy for patients with TNBC.

  19. Association Between Travel Distance and Choice of Treatment for Prostate Cancer: Does Geography Reduce Patient Choice?

    Energy Technology Data Exchange (ETDEWEB)

    Muralidhar, Vinayak, E-mail: vmuralidhar@partners.org [Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States); Rose, Brent S.; Chen, Yu-Wei; Nezolosky, Michelle D.; Nguyen, Paul L. [Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    2016-10-01

    Objective: To determine whether the distance between a prostate cancer patient's home and treatment facility was related to the choice of treatment received among those opting for surgery or radiation. Methods and Materials: We identified 222,804 patients diagnosed with National Comprehensive Cancer Network low-, intermediate-, or high-risk N0M0 prostate cancer and treated with local therapy (surgery or radiation alone, with or without hormone therapy) using the National Cancer Database. We used multivariable logistic regression to determine whether the choice of radiation therapy vs radical prostatectomy varied by distance among patients living in rural and urban areas. Analyses were adjusted for geographic location within the United States, age, race, Charlson/Deyo comorbidity score, year of diagnosis, income quartile, education quartile, Gleason score, prostate-specific antigen level, and T stage. Results: Patients living in urban or rural areas were less likely to receive radiation compared with surgery if they lived farther from the treatment facility. Among urban patients living ≤5 miles from the treatment facility, 53.3% received radiation, compared with 47.0%, 43.6%, and 33.8% of those living 5 to 10, 10 to 15, or >15 miles away, respectively (P<.001 in all cases). Similarly, rural patients were less likely to receive radiation the farther they lived from the treatment facility (≤25 miles: 62.3%; 25-50 miles: 55.5%; 50-75 miles: 38.4%; >75 miles: 23.8%; P<.05 in all cases). These trends were also present when each risk group was analyzed separately. Conclusion: Patients with prostate cancer in both urban and rural settings were less likely to receive radiation therapy rather than surgery the farther away they lived from a treatment center. These findings raise the possibility that the geographic availability of radiation treatment centers may be an important determinant of whether patients are able to choose radiation rather than surgery for

  20. Reducing Cancer Health Disparities through Community Engagement: Working with Faith-Based Organizations (Project CHURCH)

    Science.gov (United States)

    Lorna H. McNeill, PhD, MPH, is Chair and Associate Professor in the Department of Health Disparities at the University of Texas MD Anderson Cancer Center. Dr. McNeill's research is on the elimination of cancer-related health disparities in minority populations. Her research has particular emphasis on understanding the influence of social contextual determinants of cancer in minorities, with a special focus of the role of physical activity as a key preventive behavior and obesity as a major cancer determinant. Her research takes place in minority and underserved communities such as public housing developments, black churches, community-based clinics and low-income neighborhoods-communities with excess cancer death rates. She has been continuously funded, receiving grants from various funding agencies (i.e., National Institutes of Health, Robert Wood Johnson Foundation, etc.), to better understand and design innovative solutions to address obesity in racial/ethnic minority communities. Dr. McNeill is PI of several community-based studies, primarily working with African American churches. One is a called Project CHURCH, an academic-faith-based partnership established to: 1) identify underlying reasons for health disparities in cancer and cancer risk factors (e.g., screening, diet) among AAs using a cohort study (N=2400), 2) engage AAs as partners in the research process, and 3) to ultimately eliminate disparities among AAs. In 2014 Dr. McNeill furthered her partnership through the Faith, Health, and Family (FHF) Collaborative. The goals of FHF are to enhance the Project CHURCH partnership to address family obesity in African Americans, strengthen the partnership by developing a larger coalition of organizations and stakeholders to address the problem, assess church and community interest in family obesity and develop an agenda to address obesity in faith settings. To date we have 50 churches as members. Dr. McNeill is also director of the Center for Community

  1. Do palliative care interventions reduce emergency department visits among patients with cancer at the end of life? A systematic review.

    Science.gov (United States)

    DiMartino, Lisa D; Weiner, Bryan J; Mayer, Deborah K; Jackson, George L; Biddle, Andrea K

    2014-12-01

    Frequent emergency department (ED) visits are an indicator of poor quality of cancer care. Coordination of care through the use of palliative care teams may limit aggressive care and improve outcomes for patients with cancer at the end of life. To systematically review the literature to determine whether palliative care interventions implemented in the hospital, home, or outpatient clinic are more effective than usual care in reducing ED visits among patients with cancer at the end of life. PubMed, EMBASE, and CINAHL databases were searched from database inception to May 7, 2014. Only randomized/non-randomized controlled trials (RCTs) and observational studies examining the effect of palliative care interventions on ED visits among adult patients with cancer with advanced disease were considered. Data were abstracted from the articles that met all the inclusion criteria. A second reviewer independently abstracted data from 2 articles and discrepancies were resolved. From 464 abstracts, 2 RCTs, 10 observational studies, and 1 non-RCT/quasi-experimental study were included. Overall there is limited evidence to support the use of palliative care interventions to reduce ED visits, although studies examining effect of hospice care and those conducted outside of the United States reported a statistically significant reduction in ED visits. Evidence regarding whether palliative care interventions implemented in the hospital, home or outpatient clinic are more effective than usual care at reducing ED visits is not strongly substantiated based on the literature reviewed. Improvements in the quality of reporting for studies examining the effect of palliative care interventions on ED use are needed.

  2. High Throughput Transcriptomics @ USEPA (Toxicology ...

    Science.gov (United States)

    The ideal chemical testing approach will provide complete coverage of all relevant toxicological responses. It should be sensitive and specific It should identify the mechanism/mode-of-action (with dose-dependence). It should identify responses relevant to the species of interest. Responses should ideally be translated into tissue-, organ-, and organism-level effects. It must be economical and scalable. Using a High Throughput Transcriptomics platform within US EPA provides broader coverage of biological activity space and toxicological MOAs and helps fill the toxicological data gap. Slide presentation at the 2016 ToxForum on using High Throughput Transcriptomics at US EPA for broader coverage biological activity space and toxicological MOAs.

  3. Motivation and the Knowledge Gap: Effects of a Campaign to Reduce Diet-Related Cancer Risk.

    Science.gov (United States)

    Viswanath, K.; And Others

    1993-01-01

    Examines whether knowledge gaps decrease when motivation to acquire information is similar among more and less educated groups. Compares two groups with differing motivations to acquire cancer and diet information in a community that received a year-long health campaign. Finds evidence of education-based differences in knowledge even among members…

  4. Preeclampsia-Associated Hormonal Profiles and Reduced Breast Cancer Risk Among Older Mothers

    National Research Council Canada - National Science Library

    Laudenslager, Mark

    2003-01-01

    ... to cases on race/ethnicity, current age, age at delivery, and breast-feeding status. A fasting blood and saliva sample was collected from each subject during the luteal phase (day 19-22) of the menstrual cycle and assayed for specific steroid and peptide hormones thought to be linked to breast cancer.

  5. Effectiveness of Mindfulness-based Therapy for Reducing Anxiety and Depression in Patients With Cancer

    Science.gov (United States)

    Zhang, Mei-Fen; Wen, Yong-Shan; Liu, Wei-Yan; Peng, Li-Fen; Wu, Xiao-Dan; Liu, Qian-Wen

    2015-01-01

    Abstract Anxiety and depression are common among patients with cancer, and are often treated with psychological interventions including mindfulness-based therapy. The aim of the study was to perform a meta-analysis of the effectiveness of mindfulness-based interventions for improving anxiety and depression in patients with cancer. Medline, the Cochrane Library, EMBASE, and Google Scholar were searched. The randomized controlled trials designed for patients diagnosed with cancer were included. Mindfulness-based interventions were provided. The outcomes assessed were the changes in anxiety and depression scores from before to after the intervention. The treatment response was determined by calculating the standardized mean difference (SMD) for individual studies and for pooled study results. Subgroup analyses by cancer type, type of therapy, and length of follow-up were performed. Seven studies, involving 469 participants who received mindfulness-based interventions and 419 participants in a control group, were included in the meta-analysis. Mindfulness-based stress reduction and art therapy were the most common interventions (5/7 studies). All studies reported anxiety and depression scores. The pooled SMD of the change in anxiety significantly favored mindfulness-based therapy over control treatment (−0.75, 95% confidence interval −1.28, −0.22, P = 0.005). Likewise, the pooled SMD of the change in depression also significantly favored mindfulness-based therapy over control (−0.90, 95% confidence interval −1.53, −0.26, P = 0.006). During the length of follow-ups less than 12 weeks, mindfulness-based therapy significantly improved anxiety for follow-up ≤12 weeks after the start of therapy, but not >12 weeks after the start of therapy. There was a lack of consistency between the studies in the type of mindfulness-based/control intervention implemented. Patients had different forms of cancer. Subgroup analyses included a relatively small number of

  6. Reduced Mortality With Partial-Breast Irradiation for Early Breast Cancer: A Meta-Analysis of Randomized Trials

    Energy Technology Data Exchange (ETDEWEB)

    Vaidya, Jayant S., E-mail: jayant.vaidya@ucl.ac.uk [Division of Surgery and Interventional Science, University College London, London (United Kingdom); Department of Surgery, Royal Free Hospital, London (United Kingdom); Department of Surgery, Whittington Health, London (United Kingdom); Bulsara, Max [Department of Biostatistics, University of Notre Dame, Fremantle, WA (Australia); Wenz, Frederik [Department of Radiation Oncology, University Medical Centre Mannheim, University of Heidelberg, Mannheim (Germany); Coombs, Nathan [Department of Surgery, Great Western Hospital, Swindon (United Kingdom); Singer, Julian [Department of Clinical Oncology, The Princess Alexandra Hospital, Harlow (United Kingdom); Ebbs, Stephen [Croydon University Hospital, Croydon (United Kingdom); Massarut, Samuele [National Cancer Institute, Centro di Riferimento Oncologico, Aviano (Italy); Saunders, Christobel [School of Surgery, University of Western Australia, Perth, WA (Australia); Douek, Michael [Department of Surgery, Kings College London, London (United Kingdom); Williams, Norman R. [Division of Surgery and Interventional Science, University College London, London (United Kingdom); Joseph, David [Departments of Radiation Oncology, and Surgery, Sir Charles Gairdner Hospital, Perth, WA (Australia); Tobias, Jeffrey S. [Department of Clinical Oncology, University College London Hospitals, London (United Kingdom); Baum, Michael [Division of Surgery and Interventional Science, University College London, London (United Kingdom)

    2016-10-01

    Purpose: With earlier detection and more effective treatment, mortality from breast cancer continues to fall and it has become increasingly important to reduce the toxicity of treatments. Partial-breast radiation therapy, which focuses radiation to the tumor bed, may achieve this aim. We analyzed mortality differences in randomized trials of partial-breast irradiation (PBI). Methods and Materials: We included data from published randomized trials of PBI (alone or as part of a risk-adapted approach) versus whole-breast irradiation (WBI) for invasive breast cancer suitable for breast-conserving therapy. We identified trials using PubMed and Google searches with the terms “partial breast irradiation” OR “intraoperative radiotherapy” OR “IMRT” OR (“accelerated” AND “radiation”) AND “randomised/randomized,” as well as through discussion with colleagues in the field. We calculated the proportion of patients who had events in each randomized arm at 5 years' follow-up and created a forest plot using Stata, version 14.1. Results: We identified 9 randomized trials of PBI versus WBI in invasive breast cancer; 5-year outcomes were available for non–breast cancer mortality in 5 trials (n=4489) and for breast cancer mortality in 4 trials (n=4231). The overall mortality was 4.9%. There was no detectable heterogeneity between the trials for any of the outcomes. There was no difference in the proportion of patients dying of breast cancer (difference, 0.000% [95% confidence interval (CI), −0.7 to +0.7]; P=.999). Non–breast cancer mortality with PBI was lower than with WBI (difference, 1.1% [95% CI, −2.1% to −0.2%]; P=.023). Total mortality with PBI was also lower than with WBI (difference, 1.3% [95% CI, −2.5% to 0.0%]; P=.05). Conclusions: Use of PBI instead of WBI in selected patients results in a lower 5-year non–breast cancer and overall mortality, amounting to a 25% reduction in relative terms. This information should be included when

  7. Reduced Mortality With Partial-Breast Irradiation for Early Breast Cancer: A Meta-Analysis of Randomized Trials

    International Nuclear Information System (INIS)

    Vaidya, Jayant S.; Bulsara, Max; Wenz, Frederik; Coombs, Nathan; Singer, Julian; Ebbs, Stephen; Massarut, Samuele; Saunders, Christobel; Douek, Michael; Williams, Norman R.; Joseph, David; Tobias, Jeffrey S.; Baum, Michael

    2016-01-01

    Purpose: With earlier detection and more effective treatment, mortality from breast cancer continues to fall and it has become increasingly important to reduce the toxicity of treatments. Partial-breast radiation therapy, which focuses radiation to the tumor bed, may achieve this aim. We analyzed mortality differences in randomized trials of partial-breast irradiation (PBI). Methods and Materials: We included data from published randomized trials of PBI (alone or as part of a risk-adapted approach) versus whole-breast irradiation (WBI) for invasive breast cancer suitable for breast-conserving therapy. We identified trials using PubMed and Google searches with the terms “partial breast irradiation” OR “intraoperative radiotherapy” OR “IMRT” OR (“accelerated” AND “radiation”) AND “randomised/randomized,” as well as through discussion with colleagues in the field. We calculated the proportion of patients who had events in each randomized arm at 5 years' follow-up and created a forest plot using Stata, version 14.1. Results: We identified 9 randomized trials of PBI versus WBI in invasive breast cancer; 5-year outcomes were available for non–breast cancer mortality in 5 trials (n=4489) and for breast cancer mortality in 4 trials (n=4231). The overall mortality was 4.9%. There was no detectable heterogeneity between the trials for any of the outcomes. There was no difference in the proportion of patients dying of breast cancer (difference, 0.000% [95% confidence interval (CI), −0.7 to +0.7]; P=.999). Non–breast cancer mortality with PBI was lower than with WBI (difference, 1.1% [95% CI, −2.1% to −0.2%]; P=.023). Total mortality with PBI was also lower than with WBI (difference, 1.3% [95% CI, −2.5% to 0.0%]; P=.05). Conclusions: Use of PBI instead of WBI in selected patients results in a lower 5-year non–breast cancer and overall mortality, amounting to a 25% reduction in relative terms. This information should be included when

  8. Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90

    Directory of Open Access Journals (Sweden)

    Alex Henke

    2016-08-01

    Full Text Available Background: Prostate cancer-associated fibroblasts (CAF can stimulate malignant progression and invasion of prostatic tumour cells via several mechanisms including those active in extracellular matrix; Methods: We isolated CAF from prostate cancer patients of Gleason Score 6–10 and confirmed their cancer-promoting activity using an in vivo tumour reconstitution assay comprised of CAF and BPH1 cells. We tested the effects of heat shock protein 90 (HSP90 inhibitors upon reconstituted tumour growth in vivo. Additionally, CAF contractility was measured in a 3D collagen contraction assay and migration was measured by scratch assay; Results: HSP90 inhibitors dipalmitoyl-radicicol and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG reduced tumour size and proliferation in CAF/BPH1 reconstituted tumours in vivo. We observed that the most contractile CAF were derived from patients with lower Gleason Score and of younger age compared with the least contractile CAF. HSP90 inhibitors radicicol and 17-DMAG inhibited contractility and reduced the migration of CAF in scratch assays. Intracellular levels of HSP70 and HSP90 were upregulated upon treatment with HSP90 inhibitors. Inhibition of HSP90 also led to a specific increase in transforming growth factor beta 2 (TGFβ2 levels in CAF; Conclusions: We suggest that HSP90 inhibitors act not only upon tumour cells, but also on CAF in the tumour microenvironment.

  9. Anti-Inflammatory Agent Indomethacin Reduces Invasion and Alters Metabolism in a Human Breast Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Ellen Ackerstaff

    2007-03-01

    Full Text Available Hostile physiological environments such as hypoxia and acidic extracellular pH, which exist in solid tumors, may promote invasion and metastasis through inflammatory responses and formation of eicosanoids. Here, we have investigated the effects of the antiinflammatory agent indomethacin on the invasion and metabolism of the human breast cancer cell line MDAMB-435 in Dulbecco's Modified Eagles (DME-based or Roswell Park Memorial Institute (RPMI-based cell medium, using a magnetic resonance-compatible invasion assay. Indomethacin treatment significantly reduced the invasion of MDA-MB-435 cells independent of the culture and perfusion conditions examined. Significant changes were detected in levels of intracellular choline phospholipid metabolites and in triglyceride (TG concentrations of these cells, depending on indomethacin treatment and basal cell medium used. Additionally, genetic profiling of breast cancer cells, grown and treated with low-dose indomethacin in cell culture using an RPMI-based medium, revealed the upregulation of several genes implicating cyclooxygenaseindependent targets of indomethacin. These data confirm the ability of an anti-inflammatory agent to reduce breast cancer invasion and demonstrate, depending on cell culture and perfusion conditions, that the indomethacin-induced decrease in invasion is associated with changes in choline phospholipid metabolism, TG metabolism, and gene expression.

  10. Simulation of reduced breast cancer mortality in breast cancer screening programs; Simulacion de la reduccion de mortalidad por cancer de mama en programas de cribado mamografico

    Energy Technology Data Exchange (ETDEWEB)

    Zamora, L. I.; Forastero, C.; Guirado, D.; Lallena, A. M.

    2011-07-01

    The breast cancer screening programs are an essential tool in the fight against breast cancer. Currently, many questions concerning the setup of these programs are open, namely: age range of women who undergo the same, frequency of mammography, ... The effectiveness of a program should be evaluated in terms of mortality reduction is its systematic implementation in the population. In this sense, we performed Monte Carlo simulations to assess that these reductions.

  11. A "package solution" fast track program can reduce the diagnostic waiting time in head and neck cancer

    DEFF Research Database (Denmark)

    Sørensen, Jesper Roed; Johansen, Jørgen; Gano, Lars

    2014-01-01

    and Neck Surgery during three comparable time intervals 2006-2007, 2007-2008, and 2011-2012 (groups 1-3) were investigated. We recorded the time from patient referral, to first consultation and final diagnosis. The first interval was before initiation of the "package solution", the second just after......In 2007, a fast track program for patients with suspicion of head and neck cancer (HNC) was introduced in Denmark to reduce unnecessary waiting time. The program was based on so called "package solutions" including pre-booked slots for outpatient evaluation, imaging, and diagnostic surgical...... procedures. The purpose of this study is to present a model for fast track handling of patients suspicious of cancer in the head and neck region and to evaluate the effect of implementation on the diagnostic work up time. Patients with suspicion of HNC referred to the same university department of ENT Head...

  12. Reducing skin cancer risk: an intervention based on protection motivation theory.

    Science.gov (United States)

    McClendon, B T; Prentice-Dunn, S

    2001-05-01

    Caucasian college students who intentionally tanned participated in a brief skin cancer intervention based on protection motivation theory (PMT). This intervention targeted skin appearance and consisted of brief lectures, a comprehensive essay, video clips about a young man who died of melanoma, and short discussions. Compared to a waitlist control group, the intervention group showed increases on PMT variables and intentions at post-test. The waitlist group later received the intervention and showed similar increases. Additionally, all but one PMT variable maintained post-test levels at a one-month follow-up. Photographs taken at post-test and at the one-month follow-up were judged by raters blind to the hypothesis. Seventy-two percent of participants were judged to have lighter skin whereas only 16 percent had darker skin. These results provide additional support for theory-based methods for changing maladaptive attitudes and behaviors associated with skin cancer risk.

  13. Triple negative breast cancers have a reduced expression of DNA repair genes.

    Directory of Open Access Journals (Sweden)

    Enilze Ribeiro

    Full Text Available DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia in paraffin embedded samples of triple negative breast cancer (TNBC compared to luminal A breast cancer (LABC. Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects.

  14. Strengthening cancer biology research, prevention, and control while reducing cancer disparities: student perceptions of a collaborative master's degree program in cancer biology, preventions, and control.

    Science.gov (United States)

    Jillson, I A; Cousin, C E; Blancato, J K

    2013-09-01

    This article provides the findings of a survey of previous and current students in the UDC/GU-LCCC master's degree program. This master's degree program, Cancer Biology, Prevention, and Control is administered and taught jointly by faculty of a Minority Serving Institution, the University of the District of Columbia, and the Lombardi Comprehensive Cancer Center to incorporate the strengths of a community-based school with a research intensive medical center. The program was initiated in 2008 through agreements with both University administrations and funding from the National Cancer Institute. The master's degree program is 36 credits with a focus on coursework in biostatistics, epidemiology, tumor biology, cancer prevention, medical ethics, and cancer outreach program design. For two semesters during the second year, students work full-time with a faculty person on a laboratory or outreach project that is a requirement for graduation. Students are supported and encouraged to transition to a doctoral degree after they obtain the master's and many of them are currently in doctorate programs. Since the inception of the program, 45 students have initiated the course of study, 28 have completed the program, and 13 are currently enrolled in the program. The survey was designed to track the students in their current activities, as well as determine which courses, program enhancements, and research experiences were the least and most useful, and to discern students' perceptions of knowledge acquired on various aspects of Cancer Biology Prevention, and Control Master's Program. Thirty of the 35 individuals to whom email requests were sent responded to the survey, for a response rate of 85.7%. The results of this study will inform the strengthening of the Cancer Biology program by the Education Advisory Committee. They can also be used in the development of comparable collaborative master's degree programs designed to address the significant disparities in prevalence of

  15. Psychological factors associated with the intention to choose for risk-reducing mastectomy in family cancer clinic attendees.

    Science.gov (United States)

    van Driel, C M G; Oosterwijk, J C; Meijers-Heijboer, E J; van Asperen, C J; Zeijlmans van Emmichoven, I A; de Vries, J; Mourits, M J E; Henneman, L; Timmermans, D R M; de Bock, G H

    2016-12-01

    Women seeking counseling because of familial breast cancer occurrence face difficult decisions, such as whether and when to opt for risk-reducing mastectomy (RRM) in case of BRCA1/2 mutation. Only limited research has been done to identify the psychological factors associated with the decision for RRM. This study investigated which psychological factors are related to the intention to choose for RRM. A cohort of 486 cancer-unaffected women with a family history of breast cancer completed the following questionnaires prior to genetic counseling: the Cancer Worry Scale, Positive And Negative Affect Scale, Perceived Personal Control Scale, Hospital Anxiety and Depression Scale and State Anxiety Scale and questions regarding socio-demographic characteristics, family history, risk perception and RRM intention. Multivariate logistic regression was used to analyze the relation between psychological factors and women's intention to choose for RRM. Factors associated with RRM intention were high positive affect (OR = 1.86, 95%CI = 1.12-3.08), high negative affect (OR = 2.52, 95%CI = 1.44-4.43), high cancer worry (OR = 1.65, 95%CI = 1.00-2.72), high perceived personal control (OR = 3.58, 95%CI = 2.18-5.89), high risk-perception (OR = 1.85, 95%CI = 1.15-2.95) and having children (OR = 2.06, 95%CI = 1.21-3.50). Negative and positive affects play an important role in the intention for RRM. Furthermore, perceived personal control over the situation is associated with an intention for RRM. In addition to focusing on accurate risk communication, counseling should pay attention to the influence of perceived control and emotions to facilitate decision-making. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Reducing confounding and suppression effects in TCGA data: an integrated analysis of chemotherapy response in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Hsu Fang-Han

    2012-10-01

    Full Text Available Abstract Background Despite initial response in adjuvant chemotherapy, ovarian cancer patients treated with the combination of paclitaxel and carboplatin frequently suffer from recurrence after few cycles of treatment, and the underlying mechanisms causing the chemoresistance remain unclear. Recently, The Cancer Genome Atlas (TCGA research network concluded an ovarian cancer study and released the dataset to the public. The TCGA dataset possesses large sample size, comprehensive molecular profiles, and clinical outcome information; however, because of the unknown molecular subtypes in ovarian cancer and the great diversity of adjuvant treatments TCGA patients went through, studying chemotherapeutic response using the TCGA data is difficult. Additionally, factors such as sample batches, patient ages, and tumor stages further confound or suppress the identification of relevant genes, and thus the biological functions and disease mechanisms. Results To address these issues, herein we propose an analysis procedure designed to reduce suppression effect by focusing on a specific chemotherapeutic treatment, and to remove confounding effects such as batch effect, patient's age, and tumor stages. The proposed procedure starts with a batch effect adjustment, followed by a rigorous sample selection process. Then, the gene expression, copy number, and methylation profiles from the TCGA ovarian cancer dataset are analyzed using a semi-supervised clustering method combined with a novel scoring function. As a result, two molecular classifications, one with poor copy number profiles and one with poor methylation profiles, enriched with unfavorable scores are identified. Compared with the samples enriched with favorable scores, these two classifications exhibit poor progression-free survival (PFS and might be associated with poor chemotherapy response specifically to the combination of paclitaxel and carboplatin. Significant genes and biological processes are

  17. Hormones and breast cancer: can we use them in ways that could reduce the risk?

    OpenAIRE

    Khalid Mahmud

    2011-01-01

    Many hormones promote or inhibit breast cancer in different ways. These effects and the mechanisms involved are reviewed in order to suggest a potentially safer use of hormones. Natural estrogens, administered transdermally, and natural progesterone may be the safest combination of female hormones. Increased intake of cruciferous vegetables could provide additional safety by improving 2-hydoxyestrone and diminishing 16 alphahydroxyestrone. Testosterone and dehydroepiandrosterone (DHEA) may di...

  18. Physical activity reduces risk for colon polyps in a multiethnic colorectal cancer screening population

    Directory of Open Access Journals (Sweden)

    Sanchez Nelson F

    2012-06-01

    Full Text Available Abstract Background Identifying modifiable factors that influence the epidemiology of colorectal cancer incidence among multiethnic groups might be informative for the development of public health strategies targeting the disease. Minimal data exists describing the impact of physical activity on colorectal polyp risk in United States minority populations. The aim of this study is to evaluate the relationship of exercise on the prevalence of polyps in a multiethnic colorectal cancer screening population. Results We enrolled 982 patients: 558 Hispanic, 202 Asian,149 Black, and 69 White. Patients who reported exercising one or more hours weekly had a lower prevalence of any polyps (25.3% vs 33.2%, P = 0.008 as well as adenomas (13.8 vs. 18.9%, P = 0.03 compared to those who did not exercise. Black and Hispanic patients and those who were overweight or obese also had lower prevalence of polyps if they led an active lifestyle. Multivariate analysis revealed that age >55, male sex, and Black race/ethnicity were positively associated with the presence of adenomas, while a history of exercising one hour or more weekly was an independent negative predictor for the presence of adenomas anywhere in the colon (OR 0.67; 95% CI 0.4 - 0.9, P = 0.03. Conclusions Exercising one hour per week was associated with a lower prevalence of polyps and adenomas when compared to those who exercised less or not at all. An active lifestyle provides benefits to groups who are at risk for colorectal cancer, such as Blacks. It also provides significant protection to overweight and obese individuals. Public health initiatives should promote physical activity as a cancer prevention tool in multiethnic populations. Trial registration none

  19. Potential impact of the MR spectroscopic cancer blood test on reducing the need for lung biopsy

    International Nuclear Information System (INIS)

    Simon, M.; Fossel, E.T.

    1989-01-01

    Lung biopsies are generally performed to identify or rule out malignancy. A clinical presumption of lung malignancy without biopsy proof may result in unjustified surgery. The authors sought to test the value of the MR cancer blood test (CBT) recently described. They obtained prebiopsy blood samples (2 mL) from 65 patients undergoing lung biopsy for radiologically identified lesions. The CBT was performed blinded, and the result was then compared with the pathologic diagnosis obtained from biopsy. Results are presented

  20. Galectin-4 Reduces Migration and Metastasis Formation of Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Ana I Belo

    Full Text Available Galectin-4 (Gal-4 is a member of the galectin family of glycan binding proteins that shows a significantly higher expression in cystic tumors of the human pancreas and in pancreatic adenocarcinomas compared to normal pancreas. However, the putative function of Gal-4 in tumor progression of pancreatic cancer is still incompletely understood. In this study the role of Gal-4 in cancer progression was investigated, using a set of defined pancreatic cancer cell lines, Pa-Tu-8988S (PaTu-S and Pa-Tu-8988T (PaTu-T, as a model. These two cell lines are derived from the same liver metastasis of a human primary pancreatic adenocarcinoma, but differ in their growth characteristics and metastatic capacity. We demonstrated that Gal-4 expression is high in PaTu-S, which shows poor migratory properties, whereas much lower Gal-4 levels are observed in the highly metastatic cell line PaTu-T. In PaTu-S, Gal-4 is found in the cytoplasm, but it is also secreted and accumulates at the membrane at sites of contact with neighboring cells. Moreover, we show that Gal-4 inhibits metastasis formation by delaying migration of pancreatic cancer cells in vitro using a scratch assay, and in vivo using zebrafish (Danio rerio as an experimental model. Our data suggest that Gal-4 may act at the cell-surface of PaTu-S as an adhesion molecule to prevent release of the tumor cells, but has in addition a cytosolic function by inhibiting migration via a yet unknown mechanism.

  1. Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer

    Directory of Open Access Journals (Sweden)

    Ma Jianjun

    2008-10-01

    Full Text Available Abstract Background NDRG2 (N-Myc downstream-regulated gene 2 was initially cloned in our laboratory. Previous results have shown that NDRG2 expressed differentially in normal and cancer tissues. Specifically, NDRG2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG2 participates in carcinogenesis of the thyroid. Methods In this study, we investigated the expression profile of human NDRG2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40 and carcinomas (n = 35, along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc. Results The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG2 expression with gender, age, different histotypes of thyroid cancers or distant metastases. Conclusion Our data indicates that NDRG2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma.

  2. Reduced expression of N-Myc downstream-regulated gene 2 in human thyroid cancer

    International Nuclear Information System (INIS)

    Zhao, Huadong; Chen, Suning; Lin, Wei; Shi, Hai; Ma, Jianjun; Liu, Xinping; Ma, Qingjiu; Yao, Libo; Zhang, Jian; Lu, Jianguo; He, Xianli; Chen, Changsheng; Li, Xiaojun; Gong, Li; Bao, Guoqiang; Fu, Qiang

    2008-01-01

    NDRG2 (N-Myc downstream-regulated gene 2) was initially cloned in our laboratory. Previous results have shown that NDRG2 expressed differentially in normal and cancer tissues. Specifically, NDRG2 mRNA was down-regulated or undetectable in several human cancers, and over-expression of NDRG2 inhibited the proliferation of cancer cells. NDRG2 also exerts important functions in cell differentiation and tumor suppression. However, it remains unclear whether NDRG2 participates in carcinogenesis of the thyroid. In this study, we investigated the expression profile of human NDRG2 in thyroid adenomas and carcinomas, by examining tissues from individuals with thyroid adenomas (n = 40) and carcinomas (n = 35), along with corresponding normal tissues. Immunohistochemistry, quantitative RT-PCR and western blot methods were utilized to determine both the protein and mRNA expression status of Ndrg2 and c-Myc. The immunostaining analysis revealed a decrease of Ndrg2 expression in thyroid carcinomas. When comparing adenomas or carcinomas with adjacent normal tissue from the same individual, the mRNA expression level of NDRG2 was significantly decreased in thyroid carcinoma tissues, while there was little difference in adenoma tissues. This differential expression was confirmed at the protein level by western blotting. However, there were no significant correlations of NDRG2 expression with gender, age, different histotypes of thyroid cancers or distant metastases. Our data indicates that NDRG2 may participate in thyroid carcinogenesis. This finding provides novel insight into the important role of NDRG2 in the development of thyroid carcinomas. Future studies are needed to address whether the down-regulation of NDRG2 is a cause or a consequence of the progression from a normal thyroid to a carcinoma

  3. BEMER Electromagnetic Field Therapy Reduces Cancer Cell Radioresistance by Enhanced ROS Formation and Induced DNA Damage.

    Directory of Open Access Journals (Sweden)

    Katja Storch

    Full Text Available Each year more than 450,000 Germans are expected to be diagnosed with cancer subsequently receiving standard multimodal therapies including surgery, chemotherapy and radiotherapy. On top, molecular-targeted agents are increasingly administered. Owing to intrinsic and acquired resistance to these therapeutic approaches, both the better molecular understanding of tumor biology and the consideration of alternative and complementary therapeutic support are warranted and open up broader and novel possibilities for therapy personalization. Particularly the latter is underpinned by the increasing utilization of non-invasive complementary and alternative medicine by the population. One investigated approach is the application of low-dose electromagnetic fields (EMF to modulate cellular processes. A particular system is the BEMER therapy as a Physical Vascular Therapy for which a normalization of the microcirculation has been demonstrated by a low-frequency, pulsed EMF pattern. Open remains whether this EMF pattern impacts on cancer cell survival upon treatment with radiotherapy, chemotherapy and the molecular-targeted agent Cetuximab inhibiting the epidermal growth factor receptor. Using more physiological, three-dimensional, matrix-based cell culture models and cancer cell lines originating from lung, head and neck, colorectal and pancreas, we show significant changes in distinct intermediates of the glycolysis and tricarboxylic acid cycle pathways and enhanced cancer cell radiosensitization associated with increased DNA double strand break numbers and higher levels of reactive oxygen species upon BEMER treatment relative to controls. Intriguingly, exposure of cells to the BEMER EMF pattern failed to result in sensitization to chemotherapy and Cetuximab. Further studies are necessary to better understand the mechanisms underlying the cellular alterations induced by the BEMER EMF pattern and to clarify the application areas for human disease.

  4. Early preventive exercises versus usual care does not seem to reduce trismus in patients treated with radiotherapy for cancer in the oral cavity or oropharynx

    DEFF Research Database (Denmark)

    Høgdal, Nina; Juhl, Carsten Bogh; Aadahl, Mette

    2015-01-01

    ABSTRACT Purpose. In head and neck cancer patients undergoing curative radiotherapy, we investigated the benefi ts and harms of an early exercise regime on trismus. Material and methods. Patients with head and neck cancer undergoing radiotherapy were centrally randomised to exercises 5 – 6 times ...... outcomes. Conclusions. In patients with cancer in the oral cavity or oropharynx, early supervised exercises combined with selfcare treatment focusing on mobility exercises to reduce...

  5. Orlistat Reduces Proliferation and Enhances Apoptosis in Human Pancreatic Cancer Cells (PANC-1).

    Science.gov (United States)

    Sokolowska, Ewa; Presler, Malgorzata; Goyke, Elzbieta; Milczarek, Ryszard; Swierczynski, Julian; Sledzinski, Tomasz

    2017-11-01

    Pancreatic cancer is a disease with very poor prognosis, and none of currently available pharmacotherapies have proven to be efficient in this indication. The aim of this study was to analyze the expression of fatty acid synthase (FASN) gene as a potential therapeutic target in proliferating human pancreatic cancer cells (PANC-1), and verify if orlistat, originally developed as an anti-obesity drug, inhibits PANC-1 proliferation. The effects of orlistat on gene expression, lipogenesis, proliferation and apoptosis was studied in PANC-1 cell culture. Expression of FASN increased during proliferation of PANC-1. Inhibition of FASN by orlistat resulted in a significant reduction of PANC-1 proliferation and enhanced apoptosis of these cells. This study showed, to our knowledge for the first time, that orlistat exhibits significant antitumor activity against PANC-1 cells. This implies that orlistat analogs with good oral bioavailability may find application in pharmacotherapy of pancreatic cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. Dietary fiber intake reduces risk for Barrett's esophagus and esophageal cancer.

    Science.gov (United States)

    Sun, Lingli; Zhang, Zhizhong; Xu, Jian; Xu, Gelin; Liu, Xinfeng

    2017-09-02

    Observational studies suggest an association between dietary fiber intake and risk of Barrett's esophagus and esophageal cancer. However, the results are inconsistent. To conduct a meta-analysis of observational studies to assess this association. All eligible studies were identified by electronic searches in PubMed and Embase through February 2015. Dose-response, subgroup, sensitivity, and publication bias analyses were performed. A total of 15 studies involving 16,885 subjects were included in the meta-analysis. The pooled odds ratio for the highest compared with the lowest dietary fiber intake was 0.52 (95% CI, 0.43-0.64). Stratified analyses for tumor subtype, study design, geographic location, fiber type, publication year, total sample size, and quality score yielded consistent results. Dose-response analysis indicated that a 10-g/d increment in dietary fiber intake was associated with a 31% reduction in Barrett's esophagus and esophageal cancer risk. Sensitivity analysis restricted to studies with control for conventional risk factors produced similar results, and omission of any single study had little effect on the overall risk estimate. Our findings indicate that dietary fiber intake is inversely associated with risk of Barrett's esophagus and esophageal cancer. Further large prospective studies are warranted.

  7. Moderate-intensity exercise reduces fatigue and improves mobility in cancer survivors: a systematic review and meta-regression

    Directory of Open Access Journals (Sweden)

    Amy M Dennett

    2016-04-01

    Full Text Available Question: Is there a dose-response effect of exercise on inflammation, fatigue and activity in cancer survivors? Design: Systematic review with meta-regression analysis of randomised trials. Participants: Adults diagnosed with cancer, regardless of specific diagnosis or treatment. Intervention: Exercise interventions including aerobic and/or resistance as a key component. Outcome measures: The primary outcome measures were markers of inflammation (including C-reactive protein and interleukins and various measures of fatigue. The secondary outcomes were: measures of activity, as defined by the World Health Organization's International Classification of Functioning, Disability and Health, including activities of daily living and measures of functional mobility (eg, 6-minute walk test, timed sit-to-stand and stair-climb tests. Risk of bias was evaluated using the PEDro scale, and overall quality of evidence was assessed using the Grades of Research, Assessment, Development and Evaluation (GRADE approach. Results: Forty-two trials involving 3816 participants were included. There was very low-quality to moderate-quality evidence that exercise results in significant reductions in fatigue (SMD 0.32, 95% CI 0.13 to 0.52 and increased walking endurance (SMD 0.77, 95% CI 0.26 to 1.28. A significant negative association was found between aerobic exercise intensity and fatigue reduction. A peak effect was found for moderate-intensity aerobic exercise for improving walking endurance. No dose-response relationship was found between exercise and markers of inflammation or exercise duration and outcomes. Rates of adherence were typically high and few adverse events were reported. Conclusions: Exercise is safe, reduces fatigue and increases endurance in cancer survivors. The results support the recommendation of prescribing moderate-intensity aerobic exercise to reduce fatigue and improve activity in people with cancer. Review registration: PROSPERO CRD

  8. Population-based screening program for reducing oral cancer mortality in 2,334,299 Taiwanese cigarette smokers and/or betel quid chewers.

    Science.gov (United States)

    Chuang, Shu-Lin; Su, William Wang-Yu; Chen, Sam Li-Sheng; Yen, Amy Ming-Fang; Wang, Cheng-Ping; Fann, Jean Ching-Yuan; Chiu, Sherry Yueh-Hsia; Lee, Yi-Chia; Chiu, Han-Mo; Chang, Dun-Cheng; Jou, Yann-Yuh; Wu, Chien-Yuan; Chen, Hsiu-Hsi; Chen, Mu-Kuan; Chiou, Shu-Ti

    2017-05-01

    To reduce oral cancer mortality, an organized, population-based screening program for the early detection of oral premalignancy and oral cancer was designed for high-risk individuals with habits of betel quid chewing, cigarette smoking, or both. The objective of this report was to evaluate the long-term effectiveness of this program in reducing the incidence of advanced disease and deaths from oral cancer. A nationwide, population-based screening program for oral cancer has been conducted in Taiwan since 2004. Residents aged ≥ 18 years with oral habits of cigarette smoking and/or betel quid chewing were invited. The standardized mortality ratio method was used to compare the observed numbers of advanced oral cancers and deaths from oral cancer among screening attendees with the expected numbers derived from mortality among nonattendees. An intention-to-treat analysis of the relative rate of reductions in advanced-stage oral cancers and oral cancer mortality also was conducted. The overall screening rate was 55.1%. The relative risk of death from oral cancer was 0.53 (95% confidence interval [CI], 0.51-0.56) as a result of screening compared with the expected risk of oral cancer deaths in the absence of screening. The corresponding relative risk was 0.74 (95% CI, 0.72-0.77) after adjusting for self-selection bias. The relative risk of advanced oral cancer for the screened group versus the nonscreened group was 0.62 (95% CI, 0.59-0.64), which increased to 0.79 (95% CI, 0.76-0.82) after adjustment for self-selection bias. An organized, population-based oral cancer screening program targeting more than 2 million Taiwanese cigarette smokers and/or betel quid chewers demonstrated the effectiveness of reducing stage III or IV oral cancers and oral cancer mortality. These evidence-based findings corroborate and support the screening strategy of oral visual inspection for the prevention of oral cancer among high-risk individuals in areas with a high incidence of oral

  9. The Effectiveness of Mindfulness-Based Cognitive Group Therapy in Reducing Negative Automatic Thoughts and Dysfunctional Attitudes in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Fatemeh Mehdipour

    2017-06-01

    Full Text Available Background This study aimed to evaluate the effectiveness of mindfulness-based cognitive group therapy (MBCT in reducing negative automatic thoughts and dysfunctional attitudes in cancer patients. Methods The study was an applied and quasi-experimental research conducted by pre- and post-testing. The sample consisted of 30 cancer patients selected by purposive sampling and randomly placed in the control and the experimental group (15 individuals per group. The members of both groups filled out the automatic thoughts questionnaire (ATQ and the dysfunctional attitudes scale (DAS-26 at the pre- and the post-test stage. The collected data were analyzed by the SPSS software and multivariate analysis of covariance (MANCOVA tests. Results The results indicated that MBCT significantly reduced negative automatic thoughts (F = 126.15, P < 0.01 and dysfunctional attitudes (F = 179.53, P < 0.01 in the experimental group at the post-test stage in comparison to the control group. Conclusions Based on the results of this study, it is essential that therapeutic centers and support forums related to patients with refractory disorders use MBCT in their programs for reducing negative automatic thoughts and dysfunctional attitudes.

  10. Can IMRT or Brachytherapy Reduce Dysphagia Associated With Chemoradiotherapy of Head and Neck Cancer? The Michigan and Rotterdam Experiences

    International Nuclear Information System (INIS)

    Eisbruch, Avraham; Levendag, Peter C.; Feng, Felix Y.; Teguh, David; Lyden, Teresa M.A.; Schmitz, Paul I.M.; Haxer, Marc; Noever, Inge; Chepeha, Douglas B.; Heijmen, Ben J.

    2007-01-01

    Purpose: Dysphagia is a major late complication of intensive chemoradiotherapy of head and neck cancer. The initial clinical results of intensity-modulated radiotherapy (IMRT), or brachytherapy, planned specifically to reduce dysphagia are presented. Patients and Methods: Previous research at Michigan University has suggested that the pharyngeal constrictors and glottic and supraglottic larynx are likely structures whose damage by chemo-RT causes dysphagia and aspiration. In a prospective Michigan trial, 36 patients with oropharyngeal (n = 31) or nasopharyngeal (n = 5) cancer underwent chemo-IMRT. IMRT cost functions included sparing noninvolved pharyngeal constrictors and the glottic and supraglottic larynx. After a review of published studies, the retropharyngeal nodes at risk were defined as the lateral, but not the medial, retropharyngeal nodes, which facilitated sparing of the swallowing structures. In Rotterdam, 77 patients with oropharyngeal cancer were treated with IMRT, three dimensional RT, or conventional RT; also one-half received brachytherapy. The dysphagia endpoints included videofluoroscopy and observer-assessed scores at Michigan and patient-reported quality-of-life instruments in both studies. Results: In both studies, the doses to the upper and middle constrictors correlated highly with the dysphagia endpoints. In addition, doses to the glottic and supraglottic larynx were significant in the Michigan series. In the Rotterdam series, brachytherapy (which reduced the doses to the swallowing structures) was the only significant factor on multivariate analysis. Conclusion: The dose-response relationships for the swallowing structures found in these studies suggest that reducing their doses, using either IMRT aimed at their sparing, or brachytherapy, might achieve clinical gains in dysphagia

  11. Modifiers of the Efficacy of Risk-Reducing Salpingo-Oophorectomy for the Prevention of Breast and Ovarian Cancer in Carriers of BRCA1 and BRCA2

    National Research Council Canada - National Science Library

    Kauff, Noah D

    2006-01-01

    .... This plan included 1) conduct of a prospective study examining modifiers of the efficacy of risk-reducing salpingo-oophorectomy for the prevention of breast and ovarian cancer in carriers of BRCA mutations; and 2...

  12. Modifiers of the Efficacy of Risk-Reducing Salpingo-Oophorectomy for the Prevention of Breast and Ovarian Cancer in Carriers of BRCA1 and BRCA2 Mutations

    National Research Council Canada - National Science Library

    Kauff, Noah

    2004-01-01

    .... This plan included 1) conduct of a prospective study examining modifiers of the efficacy of risk-reducing salpingo-oophorectomy for the prevention of breast and ovarian cancer in carriers of BRCA mutations; and 2...

  13. Reduced Circumferential Resection Margin Involvement in Rectal Cancer Surgery: Results of the Dutch Surgical Colorectal Audit.

    Science.gov (United States)

    Gietelink, Lieke; Wouters, Michel W J M; Tanis, Pieter J; Deken, Marion M; Ten Berge, Martijn G; Tollenaar, Rob A E M; van Krieken, J Han; de Noo, Mirre E

    2015-09-01

    The circumferential resection margin (CRM) is a significant prognostic factor for local recurrence, distant metastasis, and survival after rectal cancer surgery. Therefore, availability of this parameter is essential. Although the Dutch total mesorectal excision trial raised awareness about CRM in the late 1990s, quality assurance on pathologic reporting was not available until the Dutch Surgical Colorectal Audit (DSCA) started in 2009. The present study describes the rates of CRM reporting and involvement since the start of the DSCA and analyzes whether improvement of these parameters can be attributed to the audit. Data from the DSCA (2009-2013) were analyzed. Reporting of CRM and CRM involvement was plotted for successive years, and variations of these parameters were analyzed in a funnelplot. Predictors of CRM involvement were determined in univariable analysis and the independent influence of year of registration on CRM involvement was analyzed in multivariable analysis. A total of 12,669 patients were included for analysis. The mean percentage of patients with a reported CRM increased from 52.7% to 94.2% (2009-2013) and interhospital variation decreased. The percentage of patients with CRM involvement decreased from 14.2% to 5.6%. In multivariable analysis, the year of DSCA registration remained a significant predictor of CRM involvement. After the introduction of the DSCA, a dramatic improvement in CRM reporting and a major decrease of CRM involvement after rectal cancer surgery have occurred. This study suggests that a national quality assurance program has been the driving force behind these achievements. Copyright © 2015 by the National Comprehensive Cancer Network.

  14. Reduced disparities and improved surgical outcomes for Asian Americans with colorectal cancer.

    Science.gov (United States)

    Mulhern, Kayln C; Wahl, Tyler S; Goss, Lauren E; Feng, Katey; Richman, Joshua S; Morris, Melanie S; Chen, Herbert; Chu, Daniel I

    2017-10-01

    Studies suggest Asian Americans may have improved oncologic outcomes compared with other ethnicities. We hypothesized that Asian Americans with colorectal cancer would have improved surgical outcomes in mortality, postoperative complications (POCs), length of stay (LOS), and readmissions compared with other racial/ethnic groups. We queried the 2011-2014 American College of Surgeons National Surgical Quality Improvement Program for patients who underwent surgery for colorectal cancer and stratified patients by race. Primary outcome was 30-d mortality with secondary outcomes including POCs, LOS, and 30-d readmission. Stepwise backward logistic regression analyses and incident rate ratio calculations were performed to identify risk factors for disparate outcomes. Of the 28,283 patients undergoing colorectal surgery for malignancy, racial/ethnic groups were divided into Caucasian American (84%), African American (12%), or Asian American (4%). On unadjusted analyses, compared with other racial/ethnic groups, Asian Americans were more likely to have normal weight, not smoke, and had lower American Society of Anesthesiologists score of 1 or 2 (P Asian Americans had the shortest LOS and the lowest rates of complications due to ileus, respiratory, and renal complications (P Asian American race was independently associated with less postoperative ileus (odds ratio 0.8, 95% confidence interval 0.66-0.98, P American and Caucasian American patients, respectively (P Asian Americans undergoing surgery for colorectal cancer have shorter LOS and fewer POCs when compared with other racial/ethnic groups without differences in 30-d mortality or readmissions. The mechanism(s) underlying these disparities will require further study, but may be a result of patient, provider, and healthcare system differences. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1.

    Science.gov (United States)

    Hinrichsen, Inga; Ernst, Benjamin Philipp; Nuber, Franziska; Passmann, Sandra; Schäfer, Dieter; Steinke, Verena; Friedrichs, Nicolaus; Plotz, Guido; Zeuzem, Stefan; Brieger, Angela

    2014-01-24

    Defects in the DNA mismatch repair (MMR) protein MLH1 are frequently observed in sporadic and hereditary colorectal cancers (CRC). Affected tumors generate much less metastatic potential than the MLH1 proficient forms. Although MLH1 has been shown to be not only involved in postreplicative MMR but also in several MMR independent processes like cytoskeletal organization, the connection between MLH1 and metastasis remains unclear. We recently identified non-erythroid spectrin αII (SPTAN1), a scaffolding protein involved in cell adhesion and motility, to interact with MLH1. In the current study, the interaction of MLH1 and SPTAN1 and its potential consequences for CRC metastasis was evaluated. Nine cancer cell lines as well as fresh and paraffin embedded colon cancer tissue from 12 patients were used in gene expression studies of SPTAN1 and MLH1. Co-expression of SPTAN1 and MLH1 was analyzed by siRNA knock down of MLH1 in HeLa, HEK293, MLH1 positive HCT116, SW480 and LoVo cells. Effects on cellular motility were determined in MLH1 deficient HCT116 and MLH1 deficient HEK293T compared to their MLH1 proficient sister cells, respectively. MLH1 deficiency is clearly associated with SPTAN1 reduction. Moreover, siRNA knock down of MLH1 decreased the mRNA level of SPTAN1 in HeLa, HEK293 as well as in MLH1 positive HCT116 cells, which indicates a co-expression of SPTAN1 by MLH1. In addition, cellular motility of MLH1 deficient HCT116 and MLH1 deficient HEK293T cells was impaired compared to the MLH1 proficient sister clones. Consequently, overexpression of SPTAN1 increased migration of MLH1 deficient cells while knock down of SPTAN1 decreased cellular mobility of MLH1 proficient cells, indicating SPTAN1-dependent migration ability. These data suggest that SPTAN1 levels decreased in concordance with MLH1 reduction and impaired cellular mobility in MLH1 deficient colon cancer cells. Therefore, aggressiveness of MLH1-positive CRC might be related to SPTAN1.

  16. Two-phase deep convolutional neural network for reducing class skewness in histopathological images based breast cancer detection.

    Science.gov (United States)

    Wahab, Noorul; Khan, Asifullah; Lee, Yeon Soo

    2017-06-01

    Different types of breast cancer are affecting lives of women across the world. Common types include Ductal carcinoma in situ (DCIS), Invasive ductal carcinoma (IDC), Tubular carcinoma, Medullary carcinoma, and Invasive lobular carcinoma (ILC). While detecting cancer, one important factor is mitotic count - showing how rapidly the cells are dividing. But the class imbalance problem, due to the small number of mitotic nuclei in comparison to the overwhelming number of non-mitotic nuclei, affects the performance of classification models. This work presents a two-phase model to mitigate the class biasness issue while classifying mitotic and non-mitotic nuclei in breast cancer histopathology images through a deep convolutional neural network (CNN). First, nuclei are segmented out using blue ratio and global binary thresholding. In Phase-1 a CNN is then trained on the segmented out 80×80 pixel patches based on a standard dataset. Hard non-mitotic examples are identified and augmented; mitotic examples are oversampled by rotation and flipping; whereas non-mitotic examples are undersampled by blue ratio histogram based k-means clustering. Based on this information from Phase-1, the dataset is modified for Phase-2 in order to reduce the effects of class imbalance. The proposed CNN architecture and data balancing technique yielded an F-measure of 0.79, and outperformed all the methods relying on specific handcrafted features, as well as those using a combination of handcrafted and CNN-generated features. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Preoperative staging of endometrial cancer using reduced field-of-view diffusion-weighted imaging: a preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Ota, Takashi; Hori, Masatoshi; Onishi, Hiromitsu; Sakane, Makoto; Tsuboyama, Takahiro; Tatsumi, Mitsuaki; Tomiyama, Noriyuki [Osaka University Graduate School of Medicine, Department of Diagnostic and Interventional Radiology, Suita, Osaka (Japan); Nakamoto, Atsushi; Narumi, Yoshifumi [Osaka Medical College, Department of Radiology, Osaka (Japan); Kimura, Tadashi [Osaka University Graduate School of Medicine, Department of Obstetrics and Gynaecology, Osaka (Japan)

    2017-12-15

    To compare the image quality and diagnostic performance of reduced field-of-view (rFOV) versus conventional full field-of-view (fFOV) diffusion-weighted (DW) imaging of endometrial cancer. Fifty women with endometrial cancer underwent preoperative rFOV and fFOV DW imaging. Two radiologists compared the image qualities of both techniques, and five radiologists assessed superficial and deep myometrial invasion using both techniques. The statistical analysis included the Wilcoxon signed-rank test and paired t-test for comparisons of image quality and mean diagnostic values. Distortion, tumour delineation, and overall image quality were significantly better with rFOV DW imaging, compared to fFOV DW imaging (P < 0.05); however, the former was inferior in noise (P < 0.05). Regarding superficial invasion, the mean accuracies of the techniques did not differ statistically (rFOV, 58.0% versus fFOV, 56.0%; P = 0.30). Regarding deep myometrial invasion, rFOV DW imaging yielded significantly better mean accuracy, specificity, and positive predictive values (88.4%, 97.8%, and 91.7%, respectively), compared with fFOV DW imaging (84.8%, 94.1%, and 77.4%, respectively; P = 0.009, 0.005, and 0.011, respectively). Compared with fFOV DW imaging, rFOV DW imaging yielded less distortion, improved image quality and, consequently, better diagnostic performance for deep myometrial invasion of endometrial cancer. (orig.)

  18. Respiratory gating during stereotactic body radiotherapy for lung cancer reduces tumor position variability.

    Science.gov (United States)

    Saito, Tetsuo; Matsuyama, Tomohiko; Toya, Ryo; Fukugawa, Yoshiyuki; Toyofuku, Takamasa; Semba, Akiko; Oya, Natsuo

    2014-01-01

    We evaluated the effects of respiratory gating on treatment accuracy in lung cancer patients undergoing lung stereotactic body radiotherapy by using electronic portal imaging device (EPID) images. Our study population consisted of 30 lung cancer patients treated with stereotactic body radiotherapy (48 Gy/4 fractions/4 to 9 days). Of these, 14 were treated with- (group A) and 16 without gating (group B); typically the patients whose tumors showed three-dimensional respiratory motion ≧5 mm were selected for gating. Tumor respiratory motion was estimated using four-dimensional computed tomography images acquired during treatment simulation. Tumor position variability during all treatment sessions was assessed by measuring the standard deviation (SD) and range of tumor displacement on EPID images. The two groups were compared for tumor respiratory motion and position variability using the Mann-Whitney U test. The median three-dimensional tumor motion during simulation was greater in group A than group B (9 mm, range 3-30 mm vs. 2 mm, range 0-4 mm; psimulation, tumor position variability in the EPID images was low and comparable to patients treated without gating. This demonstrates the benefit of respiratory gating.

  19. Ghrelin may reduce radiation-induced mucositis and anorexia in head-neck cancer.

    Science.gov (United States)

    Guney, Yildiz; Ozel Turkcu, Ummuhani; Hicsonmez, Ayse; Nalca Andrieu, Meltem; Kurtman, Cengiz

    2007-01-01

    Body weight loss is common in cancer patients, and is often associated with poor prognosis, it greatly impairs quality of life (QOL). Radiation therapy (RT) is used in head and neck cancers (HNC) either as a primary treatment or as an adjuvant therapy to surgery. Patients with HNC are most susceptible to malnutrition especially due to anorexia, which is aggravated by RT. Multiple pro-inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1beta (IL-1beta), interferon (IFN)-gamma and tumor necrosis factor-alpha(TNF-alpha), have been all associated with the development of both anorexia and oral mucositis. Radiation-induced mucositis occurs in almost all patients, who are treated for HNC, it could also cause weight loss. Ghrelin is a novel 28-amino acid peptide, which up-regulates body weight through appetite control, increase food intake, down-regulate energy expenditure and induces adiposity. Furthermore, ghrelin inhibits pro-inflammatory cytokines such as IL-1alpha, IL-1beta, TNF-alpha which may cause oral mucositis and aneroxia, which are the results of weight loss. Thus weight loss during RT is an early indicator of nutritional decline, we propose that recombinant ghrelin used prophylactically could be useful as an appetite stimulant; and preventive of mucositis because of its anti-inflammatory effect, it might help patients maintain weight over the course of curative RT of the HNC and can improve specific aspects of QOL. This issue warrants further studies.

  20. An in vitro evaluation of graphene oxide reduced by Ganoderma spp. in human breast cancer cells (MDA-MB-231

    Directory of Open Access Journals (Sweden)

    Gurunathan S

    2014-04-01

    Full Text Available Sangiliyandi Gurunathan,1,2 JaeWoong Han,1 Jung Hyun Park,1 Jin Hoi Kim1 1Department of Animal Biotechnology, Konkuk University, Seoul, South Korea; 2GS Institute of Bio and Nanotechnology, Coimbatore, Tamilnadu, India Background: Recently, graphene and graphene-related materials have attracted much attention due their unique properties, such as their physical, chemical, and biocompatibility properties. This study aimed to determine the cytotoxic effects of graphene oxide (GO that is reduced biologically using Ganoderma spp. mushroom extracts in MDA-MB-231 human breast cancer cells. Methods: Herein, we describe a facile and green method for the reduction of GO using extracts of Ganoderma spp. as a reducing agent. GO was reduced without any hazardous chemicals in an aqueous solution, and the reduced GO was characterized using a range of analytical procedures. The Ganoderma extract (GE-reduced GO (GE-rGO was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, dynamic light scattering, scanning electron microscopy, Raman spectroscopy, and atomic force microscopy. Furthermore, the toxicity of GE-rGO was evaluated using a sequence of assays such as cell viability, lactate dehydrogenase leakage, and reactive oxygen species generation in human breast cancer cells (MDA-MB-231. Results: The preliminary characterization of reduction of GO was confirmed by the red-shifting of the absorption peak for GE-rGO to 265 nm from 230 nm. The size of GO and GE-rGO was found to be 1,880 and 3,200 nm, respectively. X-ray diffraction results confirmed that reduction processes of GO and the processes of removing intercalated water molecules and the oxide groups. The surface functionalities and chemical natures of GO and GE-rGO were confirmed using Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. The surface morphologies of the synthesized

  1. Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients

    Directory of Open Access Journals (Sweden)

    Coco Claudio

    2012-09-01

    Full Text Available Abstract Background Expression levels of CD133, a cancer stem cell marker, and of the α-subunit of the dystroglycan (α-DG complex, have been previously reported to be altered in colorectal cancers. Methods Expression levels of CD133 and α-DG were assessed by immunohistochemistry in a series of colon cancers and their prognostic significance was evaluated. Results Scattered cells positive for CD133 were rarely detected at the bases of the crypts in normal colonic mucosa while in cancer cells the median percentage of positive cells was 5% (range 0–80. A significant correlation was observed with pT parameter and tumor stage but not with tumor grade and N status. Recurrence and death from disease were significantly more frequent in CD133-high expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor groups for both disease-free (p = 0.002 and overall (p = 0.008 survival. Expression of α-DG was reduced in a significant fraction of tumors but low α-DG staining did not correlate with any of the classical clinical-pathological parameters. Recurrence and death from the disease were significantly more frequent in α-DG-low expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor tumors for both disease-free (p = 0.02 and overall (p = 0.02 survival. Increased expression of CD133, but not loss of α-DG, confirmed to be an independent prognostic parameters at a multivariate analysis associated with an increased risk of recurrence (RR = 2.4; p = 0.002 and death (RR = 2.3; p = 0.003. Conclusions Loss of α-DG and increased CD133 expression are frequent events in human colon cancer and evaluation of CD133 expression could help to identify high-risk colon cancer patients.

  2. Reducing the Cost of Proton Radiation Therapy: The Feasibility of a Streamlined Treatment Technique for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Newhauser, Wayne D., E-mail: newhauser@lsu.edu [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803 (United States); Department of Physics, Mary Bird Perkins Cancer Center, 4950 Essen Lane, Baton Rouge, LA 70809 (United States); Zhang, Rui [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803 (United States); Department of Physics, Mary Bird Perkins Cancer Center, 4950 Essen Lane, Baton Rouge, LA 70809 (United States); Departments of Radiation Physics and Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030 (United States); Jones, Timothy G. [Departments of Radiation Physics and Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030 (United States); Department of Physics, Abilene Christian University, ACU Box 27963, Abilene, TX 79699 (United States); Giebeler, Annelise; Taddei, Phillip J. [Departments of Radiation Physics and Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, TX 77030 (United States); Stewart, Robert D. [Department of Radiation Oncology, University of Washington School of Medicine, 1959 NE Pacific Street, Box 356043, Seattle, WA 98195 (United States); Lee, Andrew [Departments of Radiation Physics and Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030 (United States); Vassiliev, Oleg [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803 (United States); Department of Physics, Mary Bird Perkins Cancer Center, 4950 Essen Lane, Baton Rouge, LA 70809 (United States)

    2015-04-24

    Proton radiation therapy is an effective modality for cancer treatments, but the cost of proton therapy is much higher compared to conventional radiotherapy and this presents a formidable barrier to most clinical practices that wish to offer proton therapy. Little attention in literature has been paid to the costs associated with collimators, range compensators and hypofractionation. The objective of this study was to evaluate the feasibility of cost-saving modifications to the present standard of care for proton treatments for prostate cancer. In particular, we quantified the dosimetric impact of a treatment technique in which custom fabricated collimators were replaced with a multileaf collimator (MLC) and the custom range compensators (RC) were eliminated. The dosimetric impacts of these modifications were assessed for 10 patients with a commercial treatment planning system (TPS) and confirmed with corresponding Monte Carlo simulations. We assessed the impact on lifetime risks of radiogenic second cancers using detailed dose reconstructions and predictive dose-risk models based on epidemiologic data. We also performed illustrative calculations, using an isoeffect model, to examine the potential for hypofractionation. Specifically, we bracketed plausible intervals of proton fraction size and total treatment dose that were equivalent to a conventional photon treatment of 79.2 Gy in 44 fractions. Our results revealed that eliminating the RC and using an MLC had negligible effect on predicted dose distributions and second cancer risks. Even modest hypofractionation strategies can yield substantial cost savings. Together, our results suggest that it is feasible to modify the standard of care to increase treatment efficiency, reduce treatment costs to patients and insurers, while preserving high treatment quality.

  3. Reducing the Cost of Proton Radiation Therapy: The Feasibility of a Streamlined Treatment Technique for Prostate Cancer

    International Nuclear Information System (INIS)

    Newhauser, Wayne D.; Zhang, Rui; Jones, Timothy G.; Giebeler, Annelise; Taddei, Phillip J.; Stewart, Robert D.; Lee, Andrew; Vassiliev, Oleg

    2015-01-01

    Proton radiation therapy is an effective modality for cancer treatments, but the cost of proton therapy is much higher compared to conventional radiotherapy and this presents a formidable barrier to most clinical practices that wish to offer proton therapy. Little attention in literature has been paid to the costs associated with collimators, range compensators and hypofractionation. The objective of this study was to evaluate the feasibility of cost-saving modifications to the present standard of care for proton treatments for prostate cancer. In particular, we quantified the dosimetric impact of a treatment technique in which custom fabricated collimators were replaced with a multileaf collimator (MLC) and the custom range compensators (RC) were eliminated. The dosimetric impacts of these modifications were assessed for 10 patients with a commercial treatment planning system (TPS) and confirmed with corresponding Monte Carlo simulations. We assessed the impact on lifetime risks of radiogenic second cancers using detailed dose reconstructions and predictive dose-risk models based on epidemiologic data. We also performed illustrative calculations, using an isoeffect model, to examine the potential for hypofractionation. Specifically, we bracketed plausible intervals of proton fraction size and total treatment dose that were equivalent to a conventional photon treatment of 79.2 Gy in 44 fractions. Our results revealed that eliminating the RC and using an MLC had negligible effect on predicted dose distributions and second cancer risks. Even modest hypofractionation strategies can yield substantial cost savings. Together, our results suggest that it is feasible to modify the standard of care to increase treatment efficiency, reduce treatment costs to patients and insurers, while preserving high treatment quality

  4. Vitamin Intake Reduce the Risk of Gastric Cancer: Meta-Analysis and Systematic Review of Randomized and Observational Studies

    Science.gov (United States)

    Geng, Qirong; Wang, Jing; Lan, Yadong; Zhan, Youqing; Xu, Dazhi

    2014-01-01

    Aim The association between vitamin intake and gastric cancer (GC) has been widely debated due to the relatively weak evidence. In this study, a meta-analysis of prospective and well designed observational studies were performed to explore this association. Methods MEDLINE, Cochrane Library, and Sciencedirect were searched for studies of vitamin consumption and gastric cancer. This produced 47 relevant studies covering 1,221,392 human subjects. Random effects models were used to estimate summary relative risk (RR). Dose-response, subgroup, sensitivity, meta-regression, and publication bias analyses were conducted. Results The RR of gastric cancer in the group with the highest vitamin intake was compared to that of the lowest intake group. Total vitamin intake was 0.78 (95% CI, 0.71−0.83). In 9 studies that individuals were given doses at least 4 times above the tolerable upper intake (UL) vitamins, the RR was 1.20 (95% CI, 0.99−1.44). However, in 17 studies that individuals received doses below the UL, the RR was 0.76 (95% CI, 0.68−0.86). Dose-response analysis was conducted on different increments in different types of vitamins (vitamin A: 1.5 mg/day, vitamin C: 100 mg/day, vitamin E: 10 mg/day) intake with a significant reduction in the risk of gastric cancer, respectively, 29% in vitamin A, 26% in vitamin C, and 24% in vitamin E. Conclusion This meta-analysis clearly demonstrated that low doses of vitamins can significantly reduce the risk of GC, especially vitamin A, vitamin C, vitamin E. PMID:25549091

  5. CX4945 suppresses the growth of castration-resistant prostate cancer cells by reducing AR-V7 expression.

    Science.gov (United States)

    Deng, Chuangzhong; Chen, Jieping; Guo, Shengjie; Wang, Yanjun; Zhou, Qianghua; Li, Zaishang; Yang, Xingping; Yu, Xingsu; Zhang, Zhenfeng; Zhou, Fangjian; Han, Hui; Yao, Kai

    2017-08-01

    The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role. A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay. Protein and mRNA levels of full-length AR (AR-FL) and AR-V7 were determined by qPCR and western blot, respectively. The nuclear translocation of p50 and p65 was assessed to reflect the activity of the NF-κB pathway. CX4945 reduced the proliferation of CRPC cells in a dose-dependent and time-dependent manner. AR-V7 rather than AR-FL was downregulated by CX4945 in both the mRNA and protein level. Furthermore, CX4945 could restore the sensitivity of CRPC cells to bicalutamide. The analysis of possible mechanisms demonstrated that the inhibition of CK2 diminished the phosphorylation of p65 at ser529 and thus attenuated the activity of the NF-κB pathway. The inhibition of CK2 by CX4945 can repress the viability of CRPC cells and restore their sensitivity to anti-androgen therapy by suppressing AR-V7. This finding presents a potential option for the treatment of prostate cancer, especially CRPC.

  6. Music Therapy Reduces Radiotherapy-Induced Fatigue in Patients With Breast or Gynecological Cancer: A Randomized Trial.

    Science.gov (United States)

    Alcântara-Silva, Tereza Raquel; de Freitas-Junior, Ruffo; Freitas, Nilceana Maya Aires; de Paula Junior, Wanderley; da Silva, Delson José; Machado, Graziela Dias Pinheiro; Ribeiro, Mayara Kelly Alves; Carneiro, Jonathas Paiva; Soares, Leonardo Ribeiro

    2018-04-01

    To investigate the influence of music therapy on the reduction of fatigue in women with breast or gynecological malignant neoplasia during radiotherapy, since it is one of the most frequent side effects of this type of treatment, and may interfere with self-esteem, social activities, and quality of life. Randomized controlled trial (control group [CG] and music therapy group [MTG]) to assess fatigue, quality of life, and symptoms of depression in women undergoing radiotherapy using the Functional Assessment of Cancer Therapy: Fatigue (FACT-F) version 4, Functional Assessment of Cancer Therapy-General (FACT-G) version 4, and Beck Depression Inventory in 3 separate times, namely, during the first week of radiotherapy, on the week of the intermediary phase, and during the last week of radiotherapy. Individual 30- to 40-minute sessions of music therapy with the presence of a trained music therapist were offered to participants. In this study, 164 women were randomized and 116 (63 CG and 53 MTG) were included in the analyses, with mean age of 52.90 years (CG) and 51.85 years (MTG). Participants in the MTG had an average of 10 music therapy sessions, totaling 509 sessions throughout the study. FACT-F results were significant regarding Trial Outcome Index ( P = .011), FACT-G ( P = .005), and FACT-F ( P = .001) for the MTG compared with the CG. Individual music therapy sessions may be effective to reduce fatigue related to cancer and symptoms of depression, as well as to improve quality of life for women with breast or gynecological cancer undergoing radiotherapy. Further well-designed research studies are needed to adequately determine the effects of music therapy on fatigue.

  7. Morpholino-Mediated Isoform Modulation of Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) Reduces Colon Cancer Xenograft Growth

    Energy Technology Data Exchange (ETDEWEB)

    Stagg, Brian C., E-mail: briancstagg@gmail.com; Uehara, Hironori; Lambert, Nathan; Rai, Ruju; Gupta, Isha; Radmall, Bryce; Bates, Taylor; Ambati, Balamurali K. [John A Moran Eye Center, University of Utah, Salt Lake City, UT, 65 Mario Capecchi Drive, Salt Lake City, UT 84132 (United States)

    2014-11-26

    Angiogenesis plays a key role in tumor growth. Vascular endothelial growth factor (VEGF) is a pro-angiogenic that is involved in tumor angiogenesis. When VEGF binds to membrane-bound vascular endothelial growth factor receptor 2 (mVEGFR2), it promotes angiogenesis. Through alternative polyadenylation, VEGFR2 is also expressed in a soluble form (sVEGFR2). sVEGFR2 sequesters VEGF and is therefore anti-angiogenic. The aim of this study was to show that treatment with a previously developed and reported antisense morpholino oligomer that shifts expression from mVEGFR2 to sVEGFR2 would lead to reduced tumor vascularization and growth in a murine colon cancer xenograft model. Xenografts were generated by implanting human HCT-116 colon cancer cells into the flanks of NMRI nu/nu mice. Treatment with the therapeutic morpholino reduced both tumor growth and tumor vascularization. Because the HCT-116 cells used for the experiments did not express VEGFR2 and because the treatment morpholino targeted mouse rather than human VEGFR2, it is likely that treatment morpholino was acting on the mouse endothelial cells rather than directly on the tumor cells.

  8. Application of biochar to soil reduces cancer risk via rice consumption: a case study in Miaoqian village, Longyan, China.

    Science.gov (United States)

    Khan, Sardar; Reid, Brian J; Li, Gang; Zhu, Yong-Guan

    2014-07-01

    Consumption of rice contaminated with potentially toxic elements (PTEs) is a major pathway for human exposure to PTEs. This is particularly true in China's so called "Cancer Villages". In this study, sewage sludge biochar (SSBC) was applied to soil (at 5% and 10%) to suppress PTE phytoavailability and as a consequence to reduce PTE levels in rice grown in mining impacted paddy soils. Risk assessment indicated that SSBC addition (10%) markedly (P≤0.05) decreased the daily intake, associated with the consumption of rice, of PTEs (As, Cd, Co, Cu, Mn, Pb and Zn by: 68, 42, 55, 29, 43, 38 and 22%, respectively). In treatments containing SSBC (10%) the health quotient (HQ) indices for PTEs (except for As, Cu and Mn) were iAs (AsIII+AsV) associated with the consumption of rice was significantly (P≤0.01) reduced by 66%. These findings suggest that SSBC could be a useful soil amendment to mitigating PTE exposure, through rice consumption, in China's "Cancer Villages". Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. A Novel Dose Constraint to Reduce Xerostomia in Head-and-Neck Cancer Patients Treated With Intensity-Modulated Radiotherapy

    International Nuclear Information System (INIS)

    Strigari, Lidia; Benassi, Marcello; Arcangeli, Giorgio; Bruzzaniti, Vicente; Giovinazzo, Giuseppe; Marucci, Laura

    2010-01-01

    Purpose: To investigate the predictors of incidence and duration of xerostomia (XT) based on parotid glands (PG), submandibular glands (SMG), and both glands taken as a whole organ (TG) in head-and-neck cancer patients treated with intensity-modulated radiotherapy. Methods and Materials: A prospective study was initiated in May 2003. Sixty-three head-and-neck patients (44 with nasopharynx cancer) were included in the analysis. Using the dose-volume histogram the PG, SMG, and TG mean doses were calculated. Unstimulated and stimulated salivary flow were measured and XT-related questionnaires were compiled before and at 3, 6, 12, 18, and 24 months after radiotherapy. Salivary gland toxicity was evaluated using the Radiation Therapy Oncology Group scale, and Grade ≥3 toxicity was used as the endpoint. The XT incidence was investigated according to descriptive statistics and univariate and multivariate analysis. The Bonferroni method was used for multiple comparison adjustment. Results: After a reduced flow at 3 months after radiotherapy, recovery of salivary flow was observed over time. Primary site and salivary gland mean doses and volumes were identified in univariate analysis as prognostic factors. Multivariate analysis confirmed that TG mean dose (p = 0.00066) and pretreatment stimulated salivary flow (p = 0.00420) are independent factors for predicting XT. Conclusion: The TG mean dose correlates with XT as assessed by Radiation Therapy Oncology Group criteria, salivary output, and XT-related questionnaires. Our results suggest that TG mean dose is a candidate dose constraint for reducing XT, requiring considerably more validation in non-nasopharyngeal cancer patients.

  10. Pregabalin reduces acute inflammatory and persistent pain associated with nerve injury and cancer in rat models of orofacial pain.

    Science.gov (United States)

    Hummig, Wagner; Kopruszinski, Caroline Machado; Chichorro, Juliana Geremias

    2014-01-01

    To assess the analgesic effect of pregabalin in orofacial models of acute inflammatory pain and of persistent pain associated with nerve injury and cancer, and so determine its effectiveness in controlling orofacial pains having different underlying mechanisms. Orofacial capsaicin and formalin tests were employed in male Wistar rats to assess the influence of pregabalin (or vehicle) pretreatment in acute pain models, and the results from these experiments were analyzed by one-way analysis of variance (ANOVA) followed by Newman Keuls post-hoc test. Pregabalin (or vehicle) treatment was also tested on the facial heat hyperalgesia that was evaluated in rats receiving injection of the inflammatory irritant carrageenan into the upper lip, as well as after constriction of the infraorbital nerve (a model of trigeminal neuropathic pain), or after inoculation of tumor cells into the facial vibrissal pad; two-way repeated measures ANOVA followed by Newman-Keuls post-hoc test was used to analyze data from these experiments. Facial grooming induced by capsaicin was abolished by pretreatment with pregabalin at 10 and 30 mg/kg. However, pregabalin failed to modify the first phase of the formalin response, but reduced the second phase at both doses (10 and 30 mg/kg). In addition, treatment of rats with pregabalin reduced the heat hyperalgesia induced by carrageenan, as well as by nerve injury and facial cancer. Pregabalin produced a marked antinociceptive effect in rat models of facial inflammatory pain as well as in facial neuropathic and cancer pain models, suggesting that it may represent an important agent for the clinical control of orofacial pain.

  11. Acupuncture in Reducing Chemotherapy-Induced Peripheral Neuropathy in Participants With Stage I-III Breast Cancer

    Science.gov (United States)

    2018-05-30

    Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage IA Breast Cancer AJCC v8; Anatomic Stage IB Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Grade 1 Peripheral Motor Neuropathy, CTCAE; Grade 1 Peripheral Sensory Neuropathy, CTCAE; Grade 2 Peripheral Motor Neuropathy, CTCAE; Grade 2 Peripheral Sensory Neuropathy, CTCAE; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage II Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8

  12. Effectiveness of Lay Health Worker Outreach in Reducing Disparities in Colorectal Cancer Screening in Vietnamese Americans

    Science.gov (United States)

    Stewart, Susan L.; Nguyen, Tung T.; Bui-Tong, Ngoc; McPhee, Stephen J.

    2015-01-01

    Objectives. We conducted a cluster randomized controlled study of a lay health worker (LHW) intervention to increase colorectal cancer (CRC) screening rates among Vietnamese Americans, who typically have lower rates than do non-Hispanic Whites. Methods. We randomized 64 LHWs to 2 arms. Each LHW recruited 10 male or female participants who had never had CRC screening (fecal occult blood test, sigmoidoscopy, or colonoscopy). Intervention LHWs led 2 educational sessions on CRC screening. Control LHWs led 2 sessions on healthy eating and physical activity. The main outcome was self-reported receipt of any CRC screening at 6 months after the intervention. We conducted the study from 2008 to 2013 in Santa Clara County, California. Results. A greater proportion of intervention participants (56%) than control participants (19%) reported receiving CRC screening (P Vietnamese Americans. Randomized controlled trials are needed to test the effectiveness of LHW outreach for other populations and other health outcomes. PMID:26270306

  13. An in vitro evaluation of graphene oxide reduced by Ganoderma spp. in human breast cancer cells (MDA-MB-231).

    Science.gov (United States)

    Gurunathan, Sangiliyandi; Han, Jaewoong; Park, Jung Hyun; Kim, Jin Hoi

    2014-01-01

    Recently, graphene and graphene-related materials have attracted much attention due their unique properties, such as their physical, chemical, and biocompatibility properties. This study aimed to determine the cytotoxic effects of graphene oxide (GO) that is reduced biologically using Ganoderma spp. mushroom extracts in MDA-MB-231 human breast cancer cells. Herein, we describe a facile and green method for the reduction of GO using extracts of Ganoderma spp. as a reducing agent. GO was reduced without any hazardous chemicals in an aqueous solution, and the reduced GO was characterized using a range of analytical procedures. The Ganoderma extract (GE)-reduced GO (GE-rGO) was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, dynamic light scattering, scanning electron microscopy, Raman spectroscopy, and atomic force microscopy. Furthermore, the toxicity of GE-rGO was evaluated using a sequence of assays such as cell viability, lactate dehydrogenase leakage, and reactive oxygen species generation in human breast cancer cells (MDA-MB-231). The preliminary characterization of reduction of GO was confirmed by the red-shifting of the absorption peak for GE-rGO to 265 nm from 230 nm. The size of GO and GE-rGO was found to be 1,880 and 3,200 nm, respectively. X-ray diffraction results confirmed that reduction processes of GO and the processes of removing intercalated water molecules and the oxide groups. The surface functionalities and chemical natures of GO and GE-rGO were confirmed using Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. The surface morphologies of the synthesized graphene were analyzed using high-resolution scanning electron microscopy. Raman spectroscopy revealed single- and multilayer properties of GE-rGO. Atomic force microscopy images provided evidence for the formation of graphene. Furthermore, the effect of GO and GE

  14. An in vitro evaluation of graphene oxide reduced by Ganoderma spp. in human breast cancer cells (MDA-MB-231)

    Science.gov (United States)

    Gurunathan, Sangiliyandi; Han, JaeWoong; Park, Jung Hyun; Kim, Jin Hoi

    2014-01-01

    Background Recently, graphene and graphene-related materials have attracted much attention due their unique properties, such as their physical, chemical, and biocompatibility properties. This study aimed to determine the cytotoxic effects of graphene oxide (GO) that is reduced biologically using Ganoderma spp. mushroom extracts in MDA-MB-231 human breast cancer cells. Methods Herein, we describe a facile and green method for the reduction of GO using extracts of Ganoderma spp. as a reducing agent. GO was reduced without any hazardous chemicals in an aqueous solution, and the reduced GO was characterized using a range of analytical procedures. The Ganoderma extract (GE)-reduced GO (GE-rGO) was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, dynamic light scattering, scanning electron microscopy, Raman spectroscopy, and atomic force microscopy. Furthermore, the toxicity of GE-rGO was evaluated using a sequence of assays such as cell viability, lactate dehydrogenase leakage, and reactive oxygen species generation in human breast cancer cells (MDA-MB-231). Results The preliminary characterization of reduction of GO was confirmed by the red-shifting of the absorption peak for GE-rGO to 265 nm from 230 nm. The size of GO and GE-rGO was found to be 1,880 and 3,200 nm, respectively. X-ray diffraction results confirmed that reduction processes of GO and the processes of removing intercalated water molecules and the oxide groups. The surface functionalities and chemical natures of GO and GE-rGO were confirmed using Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. The surface morphologies of the synthesized graphene were analyzed using high-resolution scanning electron microscopy. Raman spectroscopy revealed single- and multilayer properties of GE-rGO. Atomic force microscopy images provided evidence for the formation of graphene

  15. Successful emergency department interventions that reduce time to antibiotics in febrile pediatric cancer patients

    Science.gov (United States)

    Spencer, Sandra; Nypaver, MIchele; Hebert, Katherine; Benner, Christopher; Stanley, Rachel; Cohen, Daniel; Rogers, Alexander; Goldstick, Jason; Mahajan, Prashant

    2017-01-01

    Children with cancer and fever are at high risk for sepsis related death. Rapid antibiotic delivery ( 38.0 C). A secondary objective was to identify interventions amenable to translation to other centers. We conducted a post project analysis of prospectively collected observational data from children < 18 years visiting these EDs during independently conducted QI projects. Comparisons were made pre to post intervention periods within each institution. All interventions were derived independently using QI methods by each institution. Successful as well as unsuccessful interventions were described and common interventions adopted by all sites identified. A total of 1032 ED patient visits were identified from the three projects. Improvement in median TTA delivery (min) pre to post intervention(s) was 118.5–57.0 at site 1, 163.0–97.5 at site 2, and 188.0–111.5 at site 3 (p<.001 all sites). The eight common interventions were 1) Triage application of topical anesthetic 2) Rapid room placement & triage 3) Resuscitation room placement of ill appearing children 4) Close proximity to central line equipment 5) Antibiotic administration before laboratory analyses 6) Consensus clinical practice guideline establishment 7) Family pre-ED education for fever and 8) Staff project updates. This core set of eight low cost, high yield QI interventions were developed independently by the three ED's which led to substantial reduction in time to antibiotic delivery in children with cancer presenting with fever. These interventions may inform future QI initiatives in other settings caring for febrile pediatric oncology patients. PMID:28321299

  16. Non-steroidal anti-inflammatory drugs use is associated with reduced risk of inflammation-associated cancers: NIH-AARP study.

    Directory of Open Access Journals (Sweden)

    Fatma M Shebl

    Full Text Available Chronic inflammation has been linked to cancers, and use of non-steroidal anti-inflammatory drugs (NSAIDs has been associated with reduced risk of several cancers. To further refine the magnitude of NSAID-related associations, in particular for cancers related to inflammation, such as alcohol-, infection-, obesity-, and smoking-related cancers, as well as for less common cancers, we evaluated the use of NSAIDs and cancer risk in a very large cohort. We used propensity scores to account for potential selection bias and hypothesized that NSAID use is associated with decreased cancer incidence.We conducted a prospective study among 314,522 participants in the NIH-AARP Diet and Health Study. Individuals who completed the lifestyle questionnaire, which included NSAID use, in 1996-1997 were followed through 2006. Information on cancer incidence was ascertained by linking to cancer registries and vital status databases.During 2,715,994 person-years of follow-up (median 10.1 person-years, there were 51,894 incident cancers. Compared with non-users of NSAIDs, individuals who reported use in the 12 months prior to interview had a significantly lower risk of all inflammation-related cancer, alcohol-related, infection-related, obesity-related, and smoking-related cancers [hazard ratio (HR (95% CI 0.90 (0.87-0.93, 0.80 (0.74-0.85, 0.82 (0.78-0.87, 0.88 (0.84-0.92, and 0.88 (0.85-0.92 respectively].After accounting for potential selection bias, our data showed an inverse association between NSAID use and alcohol-related, infection-related, obesity-related, and smoking-related cancers and support the hypothesis that inflammation is related to an increased risk of certain cancers.

  17. Risk-reducing Salpingo-Oophorectomy in Women at Higher Risk of Ovarian and Breast Cancer: A Single Institution Prospective Series.

    Science.gov (United States)

    Ricciardi, Enzo; Tomao, Federica; Aletti, Giovanni; Bazzurini, Luca; Bocciolone, Luca; Boveri, Sara; Landoni, Fabio; Lapresa, Maria Teresa; Maruccio, Matteo; Parma, Gabriella; Peccatori, Fedro; Petrella, Maria Cristina; Zanagnolo, Vanna; Colombo, Nicoletta; Maggioni, Angelo

    2017-09-01

    Occult cancers' reported rates vary from 2-12% and serous tubal intraepithelial carcinomas (STICs) have been identified in 3-12% of the prophylactically removed tubes of women carrying a BRCA mutation. The aim of this study was to evaluate the incidence of tubal minor epithelial atypia (STIL), STIC, and occult invasive cancer and to evaluate the cancer-specific mortality in a prospective series of women at higher risk of ovarian and breast cancer undergoing risk-reducing salpingo-oophorectomy (RRSO) n a tertiary cancer center. A series of RRSO specimens (including endometrial biopsy) from women carrying a BRCA mutation, BRCA-unknown and BRCA-negative were collected between January 1998 and April 2016 at the Division of Gynecology at the European Institute of Oncology. Inclusion criteria were: asymptomatic women who had a negative gynecologic screening within 3 months prior to RRSO. Exclusion criteria were: women with ovarian/tubal cancer prior to RRSO. A total of 411 women underwent RRSO. Median age at RRSO was 47.0 years (range=32-70 years); 75.2% had a history of breast cancer. Fifteen women were diagnosed with an occult cancer (7 STIC, 4 invasive cancers, 2 breast cancers metastatic to the adnexa, 2 endometrial cancer) (3.6%). Sixteen showed a STIL (3.9%). When excluding cases with preoperative positive markers, the occult invasive cancer rate drops to 1.5%. Our study, covering an 18-year period, shows a substantial low risk of occult cancer among a high-risk population of women undergoing RRSO. Our data still support the indication for RRSO in higher-risk patients. An endometrial biopsy should also be routinely obtained as it raises the chances of detecting occult endometrial cancers that may be otherwise missed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Diet and cancer

    Science.gov (United States)

    Fiber and cancer; Cancer and fiber; Nitrates and cancer; Cancer and nitrates ... DIET AND BREAST CANCER The link between nutrition and breast cancer has been well studied. To reduce risk of breast cancer the American ...

  19. MutY-Homolog (MYH) inhibition reduces pancreatic cancer cell growth and increases chemosensitivity.

    Science.gov (United States)

    Sharbeen, George; Youkhana, Janet; Mawson, Amanda; McCarroll, Joshua; Nunez, Andrea; Biankin, Andrew; Johns, Amber; Goldstein, David; Phillips, Phoebe

    2017-02-07

    Patients with pancreatic ductal adenocarcinoma (PC) have a poor prognosis due to metastases and chemoresistance. PC is characterized by extensive fibrosis, which creates a hypoxic microenvironment, and leads to increased chemoresistance and intracellular oxidative stress. Thus, proteins that protect against oxidative stress are potential therapeutic targets for PC. A key protein that maintains genomic integrity against oxidative damage is MutY-Homolog (MYH). No prior studies have investigated the function of MYH in PC cells. Using siRNA, we showed that knockdown of MYH in PC cells 1) reduced PC cell proliferation and increased apoptosis; 2) further decreased PC cell growth in the presence of oxidative stress and chemotherapy agents (gemcitabine, paclitaxel and vincristine); 3) reduced PC cell metastatic potential; and 4) decreased PC tumor growth in a subcutaneous mouse model in vivo. The results from this study suggest MYH may be a novel therapeutic target for PC that could potentially improve patient outcome by reducing PC cell survival, increasing the efficacy of existing drugs and reducing metastatic spread.

  20. Elucidating the transcriptome of Fasciola hepatica - a key to fundamental and biotechnological discoveries for a neglected parasite.

    Science.gov (United States)

    Young, Neil D; Hall, Ross S; Jex, Aaron R; Cantacessi, Cinzia; Gasser, Robin B

    2010-01-01

    Liver flukes of animals are parasitic flatworms (Platyhelminthes: Digenea) of major socioeconomic importance in many countries. Key representatives, such as Fasciola hepatica and F. gigantica, cause "liver fluke disease" (= fascioliasis), which is of major animal health significance worldwide. In particular, F. hepatica is a leading cause of production losses to the livestock (mainly sheep and cattle) and meat industries due to clinical disease, reduced weight gain and milk production, and deaths. This parasite is also a major food-borne pathogen of humans throughout parts of the Middle East, Asia and South America. Currently, there is a significant focus on the development of new approaches for the prevention and control of fascioliasis in livestock. Recent technological advances in genomics and bioinformatics provide unique opportunities for the identification and prevalidation of drug targets and vaccines through a better understanding of the biology of F. hepatica and related species as well as their relationship with their hosts at the molecular level. Surprisingly, despite the widespread socioeconomic impact of fascioliasis, genomic datasets for F. hepatica are scant, limiting the molecular biological research of this parasite. The present article explores specifically the transcriptome of the adult stage of F. hepatica using an integrated genomic-bioinformatic platform. The analysis of the current data reveals numerous molecules of biological relevance, some of which are inferred to be involved in key biological processes or pathways that could serve as targets for new trematocidal drugs or vaccines. Improved insights into the transcriptome of F. hepatica should pave the way for future, comparative analysis of the transcriptomes of other developmental stages of this and related parasites, such as F. gigantica, cancer-causing flatworms (Clonorchis sinensis and Opisthorchis viverrini) and blood flukes (Schistosoma mansoni and S. japonicum). Prediction of the

  1. Smoking cessation programmes in radon affected areas: can they make a significant contribution to reducing radon-induced lung cancers?

    International Nuclear Information System (INIS)

    Denman, A.R.; Groves-Kirkby, C.J.; Timson, K.; Shield, G.; Rogers, S.; Phillips, P.S.

    2008-01-01

    Domestic radon levels in parts of the UK are sufficiently high to increase the risk of lung cancer in the occupants. Public health campaigns in Northamptonshire, a designated radon affected area with 6.3% of homes having average radon levels over the UK action level of 200 Bq m -3 , have encouraged householders to test for radon and then to carry out remediation in their homes, but have been only partially successful. Only 40% of Northamptonshire houses have been tested, and only 15% of householders finding raised levels proceed to remediate. Of those who did remediate, only 9% smoked, compared to a countywide average of 28.8%. This is unfortunate, since radon and smoking combine to place the individual at higher risk by a factor of around 4, and suggests that current strategies to reduce domestic radon exposure are not reaching those most at risk. During 2004-5, the NHS Stop Smoking Services in Northamptonshire assisted 2,808 smokers to quit to the 4-week stage, with some 30% of 4-week quitters remaining quitters at 1 year. We consider whether smoking cessation campaigns make significant contributions to radon risk reduction on their own, by assessing individual occupants' risk of developing lung cancer from knowledge of their age, gender, and smoking habits, together with he radon level in their house. The results demonstrate that smoking cessation programmes have significant added value in radon affected areas, and contribute a greater health benefit than reducing radon levels in the smokers' homes, whilst they remain smokers. Additionally, results are presented from a questionnaire-based survey of quitters, addressing their reasons for seeking help in quitting smoking, and whether knowledge of radon risks influenced this decision. The impact of these findings on future public health campaigns to reduce the impact of radon and smoking are discussed. (author)

  2. Gas in the rectum tends to reduce during radical external beam radiotherapy for localised prostate cancer

    International Nuclear Information System (INIS)

    Nakamura, Naoki; Mizuno, Norifumo; Endo, Haruna; Ogita, Mami; Kawamori, Jiro; Sekigucho, Kenji; Hatanaka, Shogo; Takahashi, Osamu; Tamaki, Seiichi; Shikama, Naoto

    2014-01-01

    This study aims to clarify the time-course of gas accumulation in the rectum during treatment as guidance for the management of rectal volumes. We reviewed 2042 sets (35.2 sets per patient) of anteroposterior and right–left mega voltage (MV) images obtained for daily set-up from 58 patients who underwent radical external beam radiotherapy for localised prostate cancer. The patients were instructed to take magnesium oxide tablets during radiotherapy. They were also encouraged to avoid foods that might cause intestinal gas during radiotherapy. Gas accumulation in the rectum was graded into three classes by the same radiation oncologist. If no gas was seen in the rectum, it was classified as grade 0. A small amount of gas was classified as grade 1, whereas a marked amount of gas that required removal was classified as grade 2. Of the 2042 sets of MV images, grades 1 and 2 gas accumulation were seen in 332 (16%) and 156 (8%), respectively. By the trend test, gas accumulation significantly decreased towards the end of treatment (P=0.02 for grade 1 or 2 and P=0.02 for grade 2). On multivariate analysis, we did not identify any significant independent predictors for either baseline gas accumulation or gas reduction. Gas accumulation tended to decrease until the end of treatment. This tendency should be reconfirmed by other institutions.

  3. Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced

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    Hellevik Turid

    2012-04-01

    Full Text Available Abstract Background Cancer-Associated Fibroblasts (CAFs are significant components of solid malignancies and play central roles in cancer sustainability, invasion and metastasis. In this study we have investigated the invasive capacity and matrix remodelling properties of human lung CAFs after exposure to ablative doses of ionizing radiation (AIR, equivalent to single fractions delivered by stereotactic ablative radiotherapy (SART for medically inoperable stage-I/II non-small-cell lung cancers. Methods CAFs were isolated from lung tumour specimens from 16 donors. Initially, intrinsic radiosensitivity was evaluated by checking viability and extent of DNA-damage response (DDR at different radiation doses. The migrative and invasive capacities of CAFs were thereafter determined after a sub-lethal single radiation dose of 18 Gy. To ascertain the mechanisms behind the altered invasive capacity of cells, expression of matrix metalloproteinases (MMPs and their endogenous inhibitors (TIMPs were measured in the conditioned media several days post-irradiation, along with expression of cell surface integrins and dynamics of focal contacts by vinculin-staining. Results Exposing CAFs to 1 × 18 Gy resulted in a potent induction of multiple nuclear DDR foci (> 9/cell with little resolution after 120 h, induced premature cellular senescence and inhibition of the proliferative, migrative and invasive capacity. AIR promoted MMP-3 and inhibited MMP-1 appearance to some extent, but did not affect expression of other major MMPs. Furthermore, surface expression of integrins α2, β1 and α5 was consistently enhanced, and a dramatic augmentation and redistribution of focal contacts was observed. Conclusions Our data indicate that ablative doses of radiation exert advantageous inhibitory effects on the proliferative, migratory and invasive capacity of lung CAFs. The reduced motility of irradiated CAFs might be a consequence of stabilized focal contacts via integrins.

  4. Reduced expression of bax in small cell lung cancer cells is not sufficient to induce cisplatin-resistance

    Directory of Open Access Journals (Sweden)

    Biagosch J

    2010-10-01

    Full Text Available Abstract Resistance to cisplatin in the course of chemotherapy contributes to the poor prognosis of small cell lung cancer (SCLC. B cell lymphoma-2 is the founding member of a large family of proteins that either promote or inhibit apoptosis. We aimed at investigating if the pro-apoptotic members Bad, Bax, Bim and Bid are involved in cisplatin-resistance. Cisplatin-resistance in the SCLC cell line H1339 was induced by repetitive exposure to cisplatin. Protein expression was quantified by Western Blot and immuno-fluorescence analysis. Protein expression was altered using siRNA interference. Four "cycles" of 0.5 μg/ml cisplatin led to partial cisplatin-resistance in H1339 cells. The expression of Bad, Bim and Bid was comparable in naïve and resistant cells while the expression of Bax was reduced in the resistant clone. But, reducing Bax expression in naïve cells did not lead to altered cisplatin sensitivity neither in H1339 nor in H187 SCLC cells. We conclude that the reduced Bax expression after exposure to cisplatin is not sufficient to induce cis-platin-resistance in SCLC cells.

  5. Enhanced antitumor efficacy and reduced systemic toxicity of sulfatide-containing nanoliposomal doxorubicin in a xenograft model of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Jia Lin

    Full Text Available Sulfatide is a glycosphingolipid known to interact with several extracellular matrix proteins, such as tenascin-C which is overexpressed in many types of cancer including that of the colon. In view of the limited success of chemotherapy in colorectal cancer and high toxicity of doxorubicin (DOX, a sulfatide-containing liposome (SCL encapsulation approach was taken to overcome these barriers. This study assessed the in vitro cytotoxicity, biodistribution, therapeutic efficacy and systemic toxicity in vivo of sulfatide-containing liposomal doxorubicin (SCL-DOX using human colonic adenocarcinoma HT-29 xenograft as the experimental model. In vitro, SCL-DOX was shown to be delivered into the nuclei and displayed prolonged retention compared with the free DOX. The use of this nanodrug delivery system to deliver DOX for treatment of tumor-bearing mice produced a much improved therapeutic efficacy in terms of tumor growth suppression and extended survival in contrast to the free drug. Furthermore, treatment of tumor-bearing mice with SCL-DOX resulted in a lower DOX uptake in the principal sites of toxicity of the free drug, namely the heart and skin, as well as reduced myelosuppression and diminished cardiotoxicity. Such natural lipid-guided nanodrug delivery systems may represent a new strategy for the development of effective anticancer chemotherapeutics targeting the tumor microenvironment for both primary tumor and micrometastases.

  6. Green tea, red wine and lemon extracts reduce experimental tumor growth and cancer drug toxicity.

    Science.gov (United States)

    Zaletok, S P; Gulua, L; Wicker, L; Shlyakhovenko, V A; Gogol, S; Orlovsky, O; Karnaushenko, O V; Verbinenko, A; Milinevska, V; Samoylenko, O; Todor, I; Turmanidze, T

    2015-12-01

    , NanoGTE, and NanoGTRW decreased the levels of malondialdehyde in heart, kidney and liver tissue of experimental animals, as well as the levels of urea and creatinine in blood serum, increased erythrocyte and platelet counts, hemoglobin content, and decreased leucocyte counts. The obtained data indicate the prospects for further development of GTE and corresponding nanocomposites as auxiliary agents in cancer chemotherapy.

  7. Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression.

    Directory of Open Access Journals (Sweden)

    Pin-Shern Chen

    Full Text Available BACKGROUND: Diosgenin, a steroidal saponin obtained from fenugreek (Trigonella foenum graecum, was found to exert anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis in a variety of tumor cells. However, the effect of diosgenin on cancer metastasis remains unclear. The aim of the study is to examine the effect of diosgenin on migration and invasion in human prostate cancer PC-3 cells. METHODS AND PRINCIPAL FINDINGS: Diosgenin inhibited proliferation of PC-3 cells in a dose-dependent manner. When treated with non-toxic doses of diosgenin, cell migration and invasion were markedly suppressed by in vitro wound healing assay and Boyden chamber invasion assay, respectively. Furthermore, diosgenin reduced the activities of matrix metalloproteinase-2 (MMP-2 and MMP-9 by gelatin zymography assay. The mRNA level of MMP-2, -9, -7 and extracellular inducer of matrix metalloproteinase (EMMPRIN were also suppressed while tissue inhibitor of metalloproteinase-2 (TIMP-2 was increased by diosgenin. In addition, diosgenin abolished the expression of vascular endothelial growth factor (VEGF in PC-3 cells and tube formation of endothelial cells. Our immunoblotting assays indicated that diosgenin potently suppressed the phosphorylation of phosphatidylinositide-3 kinase (PI3K, Akt, extracellular signal regulating kinase (ERK and c-Jun N-terminal kinase (JNK. In addition, diosgenin significantly decreased the nuclear level of nuclear factor kappa B (NF-κB, suggesting that diosgenin inhibited NF-κB activity. CONCLUSION/SIGNIFICANCE: The results suggested that diosgenin inhibited migration and invasion of PC-3 cells by reducing MMPs expression. It also inhibited ERK, JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for diosgenin in anti-metastatic therapy.

  8. Target tailoring and proton beam therapy to reduce small bowel dose in cervical cancer radiotherapy. A comparison of benefits

    International Nuclear Information System (INIS)

    Boer, Peter de; Westerveld, Henrike; Smit, Mark; Bel, Arjan; Rasch, Coen R.N.; Stalpers, Lukas J.A.; Schoot, Agustinus J.A.J. van de; Buist, Marrije R.

    2018-01-01

    The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT). The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V 15Gy , V 30Gy , V 45Gy and D mean for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for ≥grade 2 acute small bowel toxicity was calculated. Both IMPT and MRI-based target tailoring resulted in significant reductions in V 15Gy , V 30Gy , V 45Gy and D mean for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of >10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This >10% NTCP reduction was expected if the V 45Gy for bowel bag was >275 cm 3 and >200 cm 3 , respectively, during standard IGART alone. In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity. (orig.) [de

  9. Adaptive radiotherapy in muscle invasive urinary bladder cancer - An effective method to reduce the irradiated bowel volume

    International Nuclear Information System (INIS)

    Tuomikoski, Laura; Collan, Juhani; Keyrilaeinen, Jani; Visapaeae, Harri; Saarilahti, Kauko; Tenhunen, Mikko

    2011-01-01

    Background and purpose: To evaluate the benefits of adaptive radiotherapy for bladder cancer in decreasing irradiation of small bowel. Material and methods: Five patients with muscle invasive bladder cancer received adaptive radiotherapy to a total dose of 55.8-65 Gy with daily cone-beam computed tomography scanning. The whole bladder was treated to 45-50.4 Gy, followed by a partial bladder boost. The plan of the day was chosen from 3 to 4 pre-planned treatment plans according to the visible extent of bladder wall in cone-beam computed tomography images. Dose volume histograms for intestinal cavity volumes were constructed and compared with corresponding histograms calculated for conventional non-adaptive radiotherapy with single treatment plan of 2 cm CTV-PTV margins. CTV dose coverage in adaptive treatment technique was compared with CTV dose coverage in conventional radiotherapy. Results: The average volume of intestinal cavity receiving ≥45 Gy was reduced from 335 ± 106 cm 3 to 180 ± 113 cm 3 (1SD). The maximum volume of intestinal cavity spared at 45 Gy on a single patient was 240 cm 3 , while the minimum volume was 65 cm 3 . The corresponding reduction in average intestinal cavity volume receiving ≥45 Gy calculated for the whole bladder treatment only was 66 ± 36 cm 3 . CTV dose coverage was improved on two out of five patients and decreased on three patients. Conclusions: Adaptive radiotherapy considerably reduces dose to the small bowel, while maintaining the dose coverage of CTV at similar level when compared to the conventional treatment technique.

  10. Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, Romaine C., E-mail: rnichols@floridaproton.org [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Huh, Soon N. [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Prado, Karl L.; Yi, Byong Y.; Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States); Ho, Meng W.; Hoppe, Bradford S.; Mendenhall, Nancy P.; Li, Zuofeng [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States)

    2012-05-01

    Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

  11. Perceived discrimination is associated with reduced breast and cervical cancer screening: the Study of Women's Health Across the Nation (SWAN).

    Science.gov (United States)

    Jacobs, Elizabeth A; Rathouz, Paul J; Karavolos, Kelly; Everson-Rose, Susan A; Janssen, Imke; Kravitz, Howard M; Lewis, Tené T; Powell, Lynda H

    2014-02-01

    Racial disparities in breast and cervical cancer screening have been documented in African American, Hispanic, and Asian populations. Perceived discrimination may contribute to this disparity. The aim of this study was to understand the relationship between perceived everyday racial/ethnic and other discrimination and receipt of breast and cervical cancer screening in a multiethnic population of women. We analyzed data from 3,258 women participating in the Study of Women's Health Across the Nation (SWAN), a multiethnic/racial, longitudinal cohort study of the natural history of the menopausal transition conducted at seven U.S. sites. Participants completed a validated measure of perceived discrimination and reasons for believing that they were treated differently, along with Pap smears, clinical breast exams (CBE), and mammography at each follow-up period. We used multiple logistic regression for the binary outcomes of having a Pap smear, CBE, or mammogram in each of the two follow-up years, using self-reported "race discrimination" and "other discrimination" at baseline as the main predictors. African American women reported the highest percentage of racial discrimination (35%), followed by Chinese (20%), Hispanic (12%), Japanese (11%), and non-Hispanic white women (3%). Non-Hispanic white women reported the highest percentage of "other" discrimination (40%), followed by Chinese (33%), African American (24%), Japanese (23%), and Hispanic women (16%). Perceived racial discrimination was not associated with reduced receipt of preventive screening, except in one fully adjusted model. Reported discrimination owing to "other" reasons, such as age or gender, was associated with reduced receipt of Pap smear (odds ratio [OR] 0.85; 95% confidence interval [CI] 0.74-0.99), CBE (OR 0.78; 95% CI 0.67-0.91), and mammography (OR 0.80; 95% CI 0.69-0.92) regardless of patient race. Perceived discrimination is an important issue across racial/ethnic groups and is negatively

  12. Infertility diagnosis has a significant impact on the transcriptome of developing blastocysts.

    Science.gov (United States)

    McCallie, Blair R; Parks, Jason C; Griffin, Darren K; Schoolcraft, William B; Katz-Jaffe, Mandy G

    2017-08-01

    Is the human blastocyst transcriptome associated with infertility diagnosis, specifically: polycystic ovaries (PCO), male factor (MF) and unexplained (UE)? The global blastocyst transcriptome was significantly altered in association with a PCO, MF and UE infertility diagnosis. Infertility diagnosis has an impact on the probability for a successful outcome following an IVF cycle. Limited information is known regarding the relationship between a specific infertility diagnosis and blastocyst transcription during preimplantation development. Blastocysts created during infertility treatment from patients with specific infertility diagnoses (PCO, MF and UE) were analyzed for global transcriptome compared to fertile donor oocyte blastocysts (control). Surplus cryopreserved blastocysts were donated with patient consent and institutional review board approval. Female patients were infertility diagnosis: PCO (n = 50), MF (n = 50), UE (n = 50) and fertile donor oocyte controls (n = 50). Pooled blastocysts were lysed for RNA isolation followed by microarray analysis using the SurePrint G3 Human Gene Expression Microarray. Validation was performed on significant genes of interest using real-time quantitative PCR (RT-qPCR). Transcription alterations were observed for all infertility etiologies compared to controls, resulting in differentially expressed genes: PCO = 869, MF = 348 and UE = 473 (P 2-fold). Functional annotation of biological and molecular processes revealed both similarities, as well as differences, across the infertility groups. All infertility etiologies displayed transcriptome alterations in signal transducer activity, receptor binding, reproduction, cell adhesion and response to stimulus. Blastocysts from PCO patients were also enriched for apoptotic genes while MF blastocysts displayed enrichment for genes involved in cancer processes. Blastocysts from couples with unexplained infertility displayed transcription alterations related to various disease states

  13. Selecting Superior De Novo Transcriptome Assemblies: Lessons Learned by Leveraging the Best Plant Genome.

    Directory of Open Access Journals (Sweden)

    Loren A Honaas

    Full Text Available Whereas de novo assemblies of RNA-Seq data are being published for a growing number of species across the tree of life, there are currently no broadly accepted methods for evaluating such assemblies. Here we present a detailed comparison of 99 transcriptome assemblies, generated with 6 de novo assemblers including CLC, Trinity, SOAP, Oases, ABySS and NextGENe. Controlled analyses of de novo assemblies for Arabidopsis thaliana and Oryza sativa transcriptomes provide new insights into the strengths and limitations of transcriptome assembly strategies. We find that the leading assemblers generate reassuringly accurate assemblies for the majority of transcripts. At the same time, we find a propensity for assemblers to fail to fully assemble highly expressed genes. Surprisingly, the instance of true chimeric assemblies is very low for all assemblers. Normalized libraries are reduced in highly abundant transcripts, but they also lack 1000s of low abundance transcripts. We conclude that the quality of de novo transcriptome assemblies is best assessed through consideration of a combination of metrics: 1 proportion of reads mapping to an assembly 2 recovery of conserved, widely expressed genes, 3 N50 length statistics, and 4 the total number of unigenes. We provide benchmark Illumina transcriptome data and introduce SCERNA, a broadly applicable modular protocol for de novo assembly improvement. Finally, our de novo assembly of the Arabidopsis leaf transcriptome revealed ~20 putative Arabidopsis genes lacking in the current annotation.

  14. Using a Reduced Spot Size for Intensity-Modulated Proton Therapy Potentially Improves Salivary Gland-Sparing in Oropharyngeal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Water, Tara A. van de, E-mail: t.a.van.de.water@rt.umcg.nl [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Lomax, Antony J. [Centre for Proton Therapy, Paul Scherrer Institute, Villigen-PSI (Switzerland); Bijl, Hendrik P.; Schilstra, Cornelis [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands); Hug, Eugen B. [Centre for Proton Therapy, Paul Scherrer Institute, Villigen-PSI (Switzerland); Langendijk, Johannes A. [Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen (Netherlands)

    2012-02-01

    Purpose: To investigate whether intensity-modulated proton therapy with a reduced spot size (rsIMPT) could further reduce the parotid and submandibular gland dose compared with previously calculated IMPT plans with a larger spot size. In addition, it was investigated whether the obtained dose reductions would theoretically translate into a reduction of normal tissue complication probabilities (NTCPs). Methods: Ten patients with N0 oropharyngeal cancer were included in a comparative treatment planning study. Both IMPT plans delivered simultaneously 70 Gy to the boost planning target volume (PTV) and 54 Gy to the elective nodal PTV. IMPT and rsIMPT used identical three-field beam arrangements. In the IMPT plans, the parotid and submandibular salivary glands were spared as much as possible. rsIMPT plans used identical dose-volume objectives for the parotid glands as those used by the IMPT plans, whereas the objectives for the submandibular glands were tightened further. NTCPs were calculated for salivary dysfunction and xerostomia. Results: Target coverage was similar for both IMPT techniques, whereas rsIMPT clearly improved target conformity. The mean doses in the parotid glands and submandibular glands were significantly lower for three-field rsIMPT (14.7 Gy and 46.9 Gy, respectively) than for three-field IMPT (16.8 Gy and 54.6 Gy, respectively). Hence, rsIMPT significantly reduced the NTCP of patient-rated xerostomia and parotid and contralateral submandibular salivary flow dysfunction (27%, 17%, and 43% respectively) compared with IMPT (39%, 20%, and 79%, respectively). In addition, mean dose values in the sublingual glands, the soft palate and oral cavity were also decreased. Obtained dose and NTCP reductions varied per patient. Conclusions: rsIMPT improved sparing of the salivary glands and reduced NTCP for xerostomia and parotid and submandibular salivary dysfunction, while maintaining similar target coverage results. It is expected that rsIMPT improves quality

  15. Strategic and Operational Plan for Integrating Transcriptomics ...

    Science.gov (United States)

    Plans for incorporating high throughput transcriptomics into the current high throughput screening activities at NCCT; the details are in the attached slide presentation presentation on plans for incorporating high throughput transcriptomics into the current high throughput screening activities at NCCT, given at the OECD meeting on June 23, 2016

  16. Strategies to reduce the systematic error due to tumor and rectum motion in radiotherapy of prostate cancer

    International Nuclear Information System (INIS)

    Hoogeman, Mischa S.; Herk, Marcel van; Bois, Josien de; Lebesque, Joos V.

    2005-01-01

    Background and purpose: The goal of this work is to develop and evaluate strategies to reduce the uncertainty in the prostate position and rectum shape that arises in the preparation stage of the radiation treatment of prostate cancer. Patients and methods: Nineteen prostate cancer patients, who were treated with 3-dimensional conformal radiotherapy, received each a planning CT scan and 8-13 repeat CT scans during the treatment period. We quantified prostate motion relative to the pelvic bone by first matching the repeat CT scans on the planning CT scan using the bony anatomy. Subsequently, each contoured prostate, including seminal vesicles, was matched on the prostate in the planning CT scan to obtain the translations and rotations. The variation in prostate position was determined in terms of the systematic, random and group mean error. We tested the performance of two correction strategies to reduce the systematic error due to prostate motion. The first strategy, the pre-treatment strategy, used only the initial rectum volume in the planning CT scan to adjust the angle of the prostate with respect to the left-right (LR) axis and the shape and position of the rectum. The second strategy, the adaptive strategy, used the data of repeat CT scans to improve the estimate of the prostate position and rectum shape during the treatment. Results: The largest component of prostate motion was a rotation around the LR axis. The systematic error (1 SD) was 5.1 deg and the random error was 3.6 deg (1 SD). The average LR-axis rotation between the planning and the repeat CT scans correlated significantly with the rectum volume in the planning CT scan (r=0.86, P<0.0001). Correction of the rotational position on the basis of the planning rectum volume alone reduced the systematic error by 28%. A correction, based on the data of the planning CT scan and 4 repeat CT scans reduced the systematic error over the complete treatment period by a factor of 2. When the correction was

  17. Physical activity reduces fatigue in patients with cancer and hematopoietic stem cell transplant recipients: A systematic review and meta-analysis of randomized trials.

    Science.gov (United States)

    Oberoi, Sapna; Robinson, Paula D; Cataudella, Danielle; Culos-Reed, S Nicole; Davis, Hailey; Duong, Nathan; Gibson, Faith; Götte, Miriam; Hinds, Pamela; Nijhof, Sanne L; Tomlinson, Deborah; van der Torre, Patrick; Cabral, Sandra; Dupuis, L Lee; Sung, Lillian

    2018-02-01

    Objective was to determine whether physical activity reduces the severity of fatigue in patients with cancer or hematopoietic stem cell transplant (HSCT) recipients. We conducted a meta-analysis of randomized trials comparing physical activity with control interventions for the management of fatigue in patients with cancer or HSCT recipients. There were 170 trials included. Physical activity reduced the severity of fatigue when compared to all control groups (standardized mean difference -0.49, 95% confidence interval -0.60 to -0.37; P fatigue although smaller effects were observed with resistance exercises (P interaction = 0.01). Other intervention and patient characteristics did not influence the effect of physical activity on the severity of fatigue. Physical activity was effective at reducing fatigue in patients with cancer and HSCT recipients across patient sub-groups. Determining the best approaches for safe implementation should be a priority. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Effectiveness of screening colonoscopy in reducing the risk of death from right and left colon cancer: a large community-based study.

    Science.gov (United States)

    Doubeni, Chyke A; Corley, Douglas A; Quinn, Virginia P; Jensen, Christopher D; Zauber, Ann G; Goodman, Michael; Johnson, Jill R; Mehta, Shivan J; Becerra, Tracy A; Zhao, Wei K; Schottinger, Joanne; Doria-Rose, V Paul; Levin, Theodore R; Weiss, Noel S; Fletcher, Robert H

    2018-02-01

    Screening colonoscopy's effectiveness in reducing colorectal cancer mortality risk in community populations is unclear, particularly for right-colon cancers, leading to recommendations against its use for screening in some countries. This study aimed to determine whether, among average-risk people, receipt of screening colonoscopy reduces the risk of dying from both right-colon and left-colon/rectal cancers. We conducted a nested case-control study with incidence-density matching in screening-eligible Kaiser Permanente members. Patients who were 55-90 years old on their colorectal cancer death date during 2006-2012 were matched on diagnosis (reference) date to controls on age, sex, health plan enrolment duration and geographical region. We excluded patients at increased colorectal cancer risk, or with prior colorectal cancer diagnosis or colectomy. The association between screening colonoscopy receipt in the 10-year period before the reference date and colorectal cancer death risk was evaluated while accounting for other screening exposures. We analysed 1747 patients who died from colorectal cancer and 3460 colorectal cancer-free controls. Compared with no endoscopic screening, receipt of a screening colonoscopy was associated with a 67% reduction in the risk of death from any colorectal cancer (adjusted OR (aOR)=0.33, 95% CI 0.21 to 0.52). By cancer location, screening colonoscopy was associated with a 65% reduction in risk of death for right-colon cancers (aOR=0.35, CI 0.18 to 0.65) and a 75% reduction for left-colon/rectal cancers (aOR=0.25, CI 0.12 to 0.53). Screening colonoscopy was associated with a substantial and comparably decreased mortality risk for both right-sided and left-sided cancers within a large community-based population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. A brief facial morphing intervention to reduce skin cancer risk behaviors: Results from a randomized controlled trial.

    Science.gov (United States)

    Blashill, Aaron J; Rooney, Benjamin M; Luberto, Christina M; Gonzales, Manuel; Grogan, Sarah

    2018-04-20

    The current study was designed to test the efficacy of an appearance-based facial morphing program to reduce intentional UV exposure among individuals at risk for skin cancer. A three-arm randomized controlled trial was employed (N = 219) comparing facial morphing + health information to: (1) mindfulness + health information; and (2) health information only. Participants were young adults with a history of recent intentional tanning and future intentions to tan. Primary outcomes were indoor and outdoor tanning frequency and tanning intentions, with secondary outcomes of tanning attitudes, body image, and affect. Facial morphing participants reported less frequent tanning, compared to mindfulness and control participants at 1-month follow-up. Facial morphing participants also generally reported lower intentions to tan at immediate follow-up, although the magnitude of these effects weakened at 1-month follow-up. Facial morphing programs may offer a brief, efficacious, and scalable augmentation to standard of care in reducing intentional UV exposure. This trial is registered with clinicaltrials.gov (NCT03237013). Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Reducing by half the percentage of late-stage presentation for breast and cervix cancer over 4 years: a pilot study of clinical downstaging in Sarawak, Malaysia.

    Science.gov (United States)

    Devi, B C R; Tang, T S; Corbex, M

    2007-07-01

    The registry of the Oncology Departmental in Sarawak General Hospital showed that 79% of nasopharyngeal, 77% of breast and 70% of cervix cancer patients were diagnosed at an advanced stage (stages III and IV) for year 1993. Hence, a low cost Early Cancer Surveillance Program was started in 1994, with the intent of downstaging these three most common cancers in Sarawak. The program consisted of (i) training health staff in hospital and rural clinics to improve their skills in early cancer detection, (ii) raising public awareness through pamphlets, posters and sensitization by health staff. Data analysis revealed that the program achieved downstaging in two of the cancers. Breast cancer in stage III and IV was reduced from 60% (1994) to 35% (1998) (P < 0.0001) and cervical cancer in stage III and IV from 60% (1994) to 26% (1998) (P < 0.0001). No reduction was observed for nasopharyngeal cancer at 88% (1994) to 91% (1998). The overall cost of this program was

  1. MicroRNA-363 targets myosin 1B to reduce cellular migration in head and neck cancer

    International Nuclear Information System (INIS)

    Chapman, Bhavana V.; Wald, Abigail I.; Akhtar, Parvez; Munko, Ana C.; Xu, Jingjing; Gibson, Sandra P.; Grandis, Jennifer R.; Ferris, Robert L.; Khan, Saleem A.

    2015-01-01

    Squamous cell carcinoma of the head and neck (SCCHN) remains a prevalent and devastating disease. Recently, there has been an increase in SCCHN cases that are associated with high-risk human papillomavirus (HPV) infection. The clinical characteristics of HPV-positive and HPV-negative SCCHN are known to be different but their molecular features are only recently beginning to emerge. MicroRNAs (miRNAs, miRs) are small, non-coding RNAs that are likely to play significant roles in cancer initiation and progression where they may act as oncogenes or tumor suppressors. Previous studies in our laboratory showed that miR-363 is overexpressed in HPV-positive compared to HPV-negative SCCHN cell lines, and the HPV type 16-E6 oncoprotein upregulates miR-363 in SCCHN cell lines. However, the functional role of miR-363 in SCCHN in the context of HPV infection remains to be elucidated. We analyzed miR-363 levels in SCCHN tumors with known HPV-status from The Cancer Genome Atlas (TCGA) and an independent cohort from our institution. Cell migration studies were conducted following the overexpression of miR-363 in HPV-negative cell lines. Bioinformatic tools and a luciferase reporter assay were utilized to confirm that miR-363 targets the 3’-UTR of myosin 1B (MYO1B). MYO1B mRNA and protein expression levels were evaluated following miR-363 overexpression in HPV-negative SCCHN cell lines. Small interfering RNA (siRNA) knockdown of MYO1B was performed to assess the phenotypic implication of reduced MYO1B expression in SCCHN cell lines. MiR-363 was found to be overexpressed in HPV-16-positive compared to the HPV-negative SCCHN tumors. Luciferase reporter assays performed in HPV-negative JHU028 cells confirmed that miR-363 targets one of its two potential binding sites in the 3’UTR of MYO1B. MYO1B mRNA and protein levels were reduced upon miR-363 overexpression in four HPV-negative SCCHN cell lines. Increased miR-363 expression or siRNA knockdown of MYO1B expression reduced

  2. Motivators and barriers of tamoxifen use as risk-reducing medication amongst women at increased breast cancer risk: a systematic literature review.

    Science.gov (United States)

    Meiser, B; Wong, W K T; Peate, M; Julian-Reynier, C; Kirk, J; Mitchell, G

    2017-01-01

    Selective estrogen receptor modulators, such as tamoxifen, reduce breast cancer risk by up to 50% in women at increased risk for breast cancer. Despite tamoxifen's well-established efficacy, many studies show that most women are not taking up tamoxifen. This systematic literature review aimed to identify the motivators and barriers to tamoxifen use 's amongst high-risk women. Using MEDLINE, PsycINFO, and Embase plus reviewing reference lists of relevant articles published between 1995 and 2016, 31 studies (published in 35 articles) were identified, which addressed high-risk women's decisions about risk-reducing medication to prevent breast cancer and were peer-reviewed primary clinical studies. A range of factors were identified as motivators of, and barriers to, tamoxifen uptake including: perceived risk, breast-cancer-related anxiety, health professional recommendation, perceived drug effectiveness, concerns about side-effects, knowledge and access to information about side-effects, beliefs about the role of risk-reducing medication, provision of a biomarker, preference for other forms of breast cancer risk reduction, previous treatment experience, concerns about randomization in clinical trial protocols and finally altruism. Results indicate that the decision for high-risk women regarding tamoxifen use or non-use as a risk-reducing medication is not straightforward. Support of women making this decision is essential and needs to encompass the full range of factors, both informational and psychological.

  3. Adjustment of serum HE4 to reduced glomerular filtration and its use in biomarker-based prediction of deep myometrial invasion in endometrial cancer

    DEFF Research Database (Denmark)

    Chovanec, Josef; Selingerova, Iveta; Greplova, Kristina

    2017-01-01

    based on single-institution data from 120 EC patients and validated against multicentric data from 379 EC patients. Results: In non-cancer individuals, serum HE4 levels increase log-linearly with reduced glomerular filtration of eGFR = 90 ml/min/1.73 m2. HE4ren, adjusting HE4 serum levels to decreased e...... levels to reduced eGFR that enables quantification of time-dependent changes in HE4 production and elimination irrespective of age and renal function in women. Utilizing HE4ren improves performance of biomarker-based models for prediction of dMI in endometrial cancer patients....

  4. Reduced selenium-binding protein 1 in breast cancer correlates with poor survival and resistance to the anti-proliferative effects of selenium.

    Directory of Open Access Journals (Sweden)

    Sheng Zhang

    Full Text Available Supplemental dietary selenium is associated with reduced incidence of many cancers. The antitumor function of selenium is thought to be mediated through selenium-binding protein 1 (SELENBP1. However, the significance of SELENBP1 expression in breast cancer is still largely unknown. A total of 95 normal and tumor tissues assay and 12 breast cancer cell lines were used in this study. We found that SELENBP1 expression in breast cancer tissues is reduced compared to normal control. Low SELENBP1 expression in ER(+ breast cancer patients was significantly associated with poor survival (p<0.01, and SELENBP1 levels progressively decreased with advancing clinical stages of breast cancer. 17-β estradiol (E2 treatment of high SELENBP1-expressing ER(+ cell lines led to a down-regulation of SELENBP1, a result that did not occur in ER(- cell lines. However, after ectopic expression of ER in an originally ER(- cell line, down-regulation of SELENBP1 upon E2 treatment was observed. In addition, selenium treatment resulted in reduced cell proliferation in endogenous SELENBP1 high cells; however, after knocking-down SELENBP1, we observed no significant reduction in cell proliferation. Similarly, selenium has no effect on inhibition of cell proliferation in low endogenous SELENBP1 cells, but the inhibitory effect is regained following ectopic SELENBP1 expression. Furthermore, E2 treatment of an ER silenced high endogenous SELENBP1 expressing cell line showed no abolishment of cell proliferation inhibition upon selenium treatment. These data indicate that SELENBP1 expression is regulated via estrogen and that the cell proliferation inhibition effect of selenium treatment is dependent on the high level of SELENBP1 expression. Therefore, the expression level of SELENBP1 could be an important marker for predicting survival and effectiveness of selenium supplementation in breast cancer. This is the first study to reveal the importance of monitoring SELENBP1 expression

  5. Reducing dose to the lungs through loosing target dose homogeneity requirement for radiotherapy of non small cell lung cancer.

    Science.gov (United States)

    Miao, Junjie; Yan, Hui; Tian, Yuan; Ma, Pan; Liu, Zhiqiang; Li, Minghui; Ren, Wenting; Chen, Jiayun; Zhang, Ye; Dai, Jianrong

    2017-11-01

    It is important to minimize lung dose during intensity-modulated radiation therapy (IMRT) of nonsmall cell lung cancer (NSCLC). In this study, an approach was proposed to reduce lung dose by relaxing the constraint of target dose homogeneity during treatment planning of IMRT. Ten NSCLC patients with lung tumor on the right side were selected. The total dose for planning target volume (PTV) was 60 Gy (2 Gy/fraction). For each patient, two IMRT plans with six beams were created in Pinnacle treatment planning system. The dose homogeneity of target was controlled by constraints on the maximum and uniform doses of target volume. One IMRT plan was made with homogeneous target dose (the resulting target dose was within 95%-107% of the prescribed dose), while another IMRT plan was made with inhomogeneous target dose (the resulting target dose was more than 95% of the prescribed dose). During plan optimization, the dose of cord and heart in two types of IMRT plans were kept nearly the same. The doses of lungs, PTV and organs at risk (OARs) between two types of IMRT plans were compared and analyzed quantitatively. For all patients, the lung dose was decreased in the IMRT plans with inhomogeneous target dose. On average, the mean dose, V5, V20, and V30 of lung were reduced by 1.4 Gy, 4.8%, 3.7%, and 1.7%, respectively, and the dose to normal tissue was also reduced. These reductions in DVH values were all statistically significant (P target dose could protect lungs better and may be considered as a choice for treating NSCLC. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  6. Specifying the ovarian cancer risk threshold of 'premenopausal risk-reducing salpingo-oophorectomy' for ovarian cancer prevention: a cost-effectiveness analysis.

    Science.gov (United States)

    Manchanda, Ranjit; Legood, Rosa; Antoniou, Antonis C; Gordeev, Vladimir S; Menon, Usha

    2016-09-01

    Risk-reducing salpingo-oophorectomy (RRSO) is the most effective intervention to prevent ovarian cancer (OC). It is only available to high-risk women with >10% lifetime OC risk. This threshold has not been formally tested for cost-effectiveness. To specify the OC risk thresholds for RRSO being cost-effective for preventing OC in premenopausal women. The costs as well as effects of surgical prevention ('RRSO') were compared over a lifetime with 'no RRSO' using a decision analysis model. RRSO was undertaken in premenopausal women >40 years. The model was evaluated at lifetime OC risk levels: 2%, 4%, 5%, 6%, 8% and 10%. Costs and outcomes are discounted at 3.5%. Uncertainty in the model was assessed using both deterministic sensitivity analysis and probabilistic sensitivity analysis (PSA). Outcomes included in the analyses were OC, breast cancer (BC) and additional deaths from coronary heart disease. Total costs and effects were estimated in terms of quality-adjusted life-years (QALYs); incidence of OC and BC; as well as incremental cost-effectiveness ratio (ICER). Published literature, Nurses Health Study, British National Formulary, Cancer Research UK, National Institute for Health and Care Excellence guidelines and National Health Service reference costs. The time horizon is lifetime and perspective: payer. Premenopausal RRSO is cost-effective at 4% OC risk (life expectancy gained=42.7 days, ICER=£19 536/QALY) with benefits largely driven by reduction in BC risk. RRSO remains cost-effective at >8.2% OC risk without hormone replacement therapy (ICER=£29 071/QALY, life expectancy gained=21.8 days) or 6%if BC risk reduction=0 (ICER=£27 212/QALY, life expectancy gained=35.3 days). Sensitivity analysis indicated results are not impacted much by costs of surgical prevention or treatment of OC/ BC or cardiovascular disease. However, results were sensitive to RRSO utility scores. Additionally, 37%, 61%, 74%, 84%, 96% and 99.5% simulations on PSA are cost

  7. Can sparing of the superficial contralateral parotid lobe reduce xerostomia following radiotherapy for head and neck cancer?

    Science.gov (United States)

    Nevens, Daan; Nuyts, Sandra

    2017-12-01

    The purpose of this study is to see whether sparing the superficial contralateral parotid lobe can help limiting xerostomia following radiotherapy for head and neck cancer. 88 patients that were included in two prospective randomized studies were analysed in the current study. Using the dosimetry of both the parotid glands, we divided our patients in four groups. Group 1 includes patients where we were able to reduce the radiation dose below the threshold in order to spare both the ipsilateral and contralateral parotid glands, Group 2 consists of patients where only the contralateral parotid gland could be spared. Group 3 consists of patients where only the contralateral superficial parotid lobe could be spared, while in Group 4 not even the contralateral superficial lobe could be spared. When we compared Group 1 and Group 2, we did not observe a significant difference between both groups in terms of xerostomia scores at 6 or 12 months. When we compared these groups with Group 3, we observed significant differences with more xerostomia in Group 3 where only the contralateral superficial lobe was spared. A significant difference was also observed between Group 3 and Group 4 with more xerostomia in Group 4. Sparing of just one superficial parotid lobe results in less xerostomia when compared to not sparing any lobe of both parotid glands. Advances in knowledge: When sparing of the whole contralateral parotid gland is not possible, delineating both the superficial parotid glands and trying to spare at least one of them can mean a way forward in limiting xerostomia in head and neck cancer patients treated with radiotherapy.

  8. Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced proinflammatory cytokines and immunosuppressive cells.

    Science.gov (United States)

    Lesinski, Gregory B; Reville, Patrick K; Mace, Thomas A; Young, Gregory S; Ahn-Jarvis, Jennifer; Thomas-Ahner, Jennifer; Vodovotz, Yael; Ameen, Zeenath; Grainger, Elizabeth; Riedl, Kenneth; Schwartz, Steven; Clinton, Steven K

    2015-11-01

    We hypothesized that soy phytochemicals may have immunomodulatory properties that may affect prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 patients with prostate cancer with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to two slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on day 56 versus baseline. Subgroup analysis indicated reduced TH1 (P = 0.028) and myeloid-derived suppressor cell (MDSC)-associated cytokines (P = 0.035). TH2 and TH17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8(+) or CD4(+) T cells but showed increased CD56(+) natural killer (NK) cells (P = 0.038). The percentage of cells with a T regulatory cell phenotype (CD4(+)CD25(+)FoxP3(+)) was significantly decreased after 56 days of soy bread (P = 0.0136). Significantly decreased monocytic (CD33(+)HLADR(neg)CD14(+)) MDSC were observed in patients consuming soy bread (P = 0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required. ©2015 American Association for Cancer Research.

  9. Cost-Effectiveness Analysis of Interventions to Reduce Risk of Aspiration in Elderly Cancer Survivors Residing in Skilled Nursing Facilities.

    Science.gov (United States)

    Mantravadi, S

    2017-04-01

    Aspiration can occur in patients of any age group, but it can be prevented. The primary population at risk is made up of survivors of cancer because of their increased risk of mucositis, mucosal atrophy, and dysphagia associated with chemotherapy, radiotherapy, and the disease process itself. The rate of incidence of aspiration cannot be quantified, because minor cases of aspiration often go unreported. Sequelae ensuing from aspirations can include pneumonia, end-stage kidney disease, dialysis, and death. Analyses of cost, decision-tree modeling, and cost effectiveness were performed to compare a hypothetical, interventional model based on best practices with usual (standard) care. A societal perspective was used as the economic view point. Direct costs, caregiver time, and market values for wages were estimated for the 2 interventions. Effectiveness values for the cost-effectiveness and decision-tree analyses were obtained from the literature. The incremental-cost-effectiveness ratio was calculated and used to compare the intervention with usual care. The interventional method was more costly but more effective than usual care. A sensitivity analysis considered the uncertainty of event probability (aspiration vs no aspiration). The interventional protocol for aspiration reduction continued to be more cost effective than usual care. Aspiration takes a financial toll on all facets of health care, including on nurses, skilled nursing facilities, patients, their families, and insurers, among others. Implementing guidelines that describe best practices for aspiration appears to be a cost-effective strategy for reducing aspirations among cancer survivors - especially elderly patients - who live in skilled nursing facilities.

  10. NURSING CARE MODEL DEVELOPMENT BY COPE APPROACH FOR REDUCING PARENT’S HOSPITALIZATION STRESS WITH CANCER CHILDREN

    Directory of Open Access Journals (Sweden)

    Ilya Krisnana

    2017-04-01

    Full Text Available Introduction: Hospitalization stress on child affect on their parents. Parent empowerment is the important aspect to develop in nursing care for reducing hospitalization stress. The objective of this study was to develop the nursing care model of reduction hospitalization stress through the COPE (creating opportunity for parent empowerment approach on the parent whose child was diagnosed cancer. Method: This study used explanative research with cross sectional design. The population were parents whose child was diagnosed cancer in pediatric hematological ward RSUD Dr. Soetomo Surabaya, conducted on 3–15th May 2012. Sample were 30 mother who met inclusion criteria: 1 toddler and preschool age, 2 first time admition on Bona 1 or Bona 2, 3read and write well and 4 noncritical condition. The independent variable were antecedens (attitude, social economic status, motivation, diffusion of innovation, empowerment (knowledge, participation, skill and environment. The dependent variable was parent’s hospitalization stress. Data were collected by using questionnaires and observation. The data were analyzed by PLS (Partial Least Square with loading factor =0.5 and T-statistic=1.96. Result: The result showed that antecedens factors affected to COPE diffusion of innovation process. Motivation was the strongest factor to influence the diffusion and innovation process (path coeffi cient=0.450;T-stat=5.278. The diffusion of innovation process affected to empowerment variable (path coeffi cient=0.487; T-stat=6.507. Discussion: It can be concluded that environment was the strongest factor as the compiler component of empowerment. Environment include physical and non-physical component. Empowerment affected to parent’s hospitalization stress with path coefficient=0.360 and T-statistik=4.980.

  11. Transcriptomic signatures in cartilage ageing

    Science.gov (United States)

    2013-01-01

    Introduction Age is an important factor in the development of osteoarthritis. Microarray studies provide insight into cartilage aging but do not reveal the full transcriptomic phenotype of chondrocytes such as small noncoding RNAs, pseudogenes, and microRNAs. RNA-Seq is a powerful technique for the interrogation of large numbers of transcripts including nonprotein coding RNAs. The aim of the study was to characterise molecular mechanisms associated with age-related changes in gene signatures. Methods RNA for gene expression analysis using RNA-Seq and real-time PCR analysis was isolated from macroscopically normal cartilage of the metacarpophalangeal joints of eight horses; four young donors (4 years old) and four old donors (>15 years old). RNA sequence libraries were prepared following ribosomal RNA depletion and sequencing was undertaken using the Illumina HiSeq 2000 platform. Differentially expressed genes were defined using Benjamini-Hochberg false discovery rate correction with a generalised linear model likelihood ratio test (P ageing cartilage. Conclusion There was an age-related dysregulation of matrix, anabolic and catabolic cartilage factors. This study has increased our knowledge of transcriptional networks in cartilage ageing by providing a global view of the transcriptome. PMID:23971731

  12. Developmental transcriptome of Aplysia californica'

    KAUST Repository

    Heyland, Andreas

    2010-12-06

    Genome-wide transcriptional changes in development provide important insight into mechanisms underlying growth, differentiation, and patterning. However, such large-scale developmental studies have been limited to a few representatives of Ecdysozoans and Chordates. Here, we characterize transcriptomes of embryonic, larval, and metamorphic development in the marine mollusc Aplysia californica and reveal novel molecular components associated with life history transitions. Specifically, we identify more than 20 signal peptides, putative hormones, and transcription factors in association with early development and metamorphic stages-many of which seem to be evolutionarily conserved elements of signal transduction pathways. We also characterize genes related to biomineralization-a critical process of molluscan development. In summary, our experiment provides the first large-scale survey of gene expression in mollusc development, and complements previous studies on the regulatory mechanisms underlying body plan patterning and the formation of larval and juvenile structures. This study serves as a resource for further functional annotation of transcripts and genes in Aplysia, specifically and molluscs in general. A comparison of the Aplysia developmental transcriptome with similar studies in the zebra fish Danio rerio, the fruit fly Drosophila melanogaster, the nematode Caenorhabditis elegans, and other studies on molluscs suggests an overall highly divergent pattern of gene regulatory mechanisms that are likely a consequence of the different developmental modes of these organisms. © 2010 Wiley-Liss, Inc., A Wiley Company.

  13. A diagnostic dilemma following risk-reducing surgery for BRCA1 mutation – a case report of primary papillary serous carcinoma presenting as sigmoid cancer

    Directory of Open Access Journals (Sweden)

    Nash Guy F

    2007-09-01

    Full Text Available Abstract Background Women that carry germ-line mutations for BRCA1 or BRCA2 genes are at an increased risk of developing breast, ovarian and peritoneal cancer. Primary peritoneal carcinoma is a rare tumour histologically identical to papillary serous ovarian carcinoma. Risk-reducing surgery in the form of mastectomy and oophorectomy in premenopausal women has been recommended to prevent breast and ovarian cancer occurrence and decrease the risk of developing primary peritoneal cancer. Case presentation We present a case report of a woman with a strong family history of breast cancer who underwent risk-reducing surgery in the form of bilateral salpingo-oophorectomy following a mastectomy for a right-sided breast tumour. Following the finding of a BRCA1 mutation, a prophylactic left-sided mastectomy was performed. After remaining well for twenty-seven years, she presented with rectal bleeding and altered bowel habit, and was found to have a secondary cancer of the sigmoid colon. She was finally diagnosed with primary papillary serous carcinoma of the peritoneum (PSCP. Conclusion PSCP can present many years after risk-reducing surgery and be difficult to detect. Surveillance remains the best course of management for patients with known BRCA mutations.

  14. Aspirin therapy reduces the ability of platelets to promote colon and pancreatic cancer cell proliferation: Implications for the oncoprotein c-MYC

    Science.gov (United States)

    Sylman, Joanna L.; Ngo, Anh T. P.; Pang, Jiaqing; Sears, Rosalie C.; Williams, Craig D.; McCarty, Owen J. T.

    2017-01-01

    Aspirin, an anti-inflammatory and antithrombotic drug, has become the focus of intense research as a potential anticancer agent owing to its ability to reduce tumor proliferation in vitro and to prevent tumorigenesis in patients. Studies have found an anticancer effect of aspirin when used in low, antiplatelet doses. However, the mechanisms through which low-dose aspirin works are poorly understood. In this study, we aimed to determine the effect of aspirin on the cross talk between platelets and cancer cells. For our study, we used two colon cancer cell lines isolated from the same donor but characterized by different metastatic potential, SW480 (nonmetastatic) and SW620 (metastatic) cancer cells, and a pancreatic cancer cell line, PANC-1 (nonmetastatic). We found that SW480 and PANC-1 cancer cell proliferation was potentiated by human platelets in a manner dependent on the upregulation and activation of the oncoprotein c-MYC. The ability of platelets to upregulate c-MYC and cancer cell proliferation was reversed by an antiplatelet concentration of aspirin. In conclusion, we show for the first time that inhibition of platelets by aspirin can affect their ability to induce cancer cell proliferation through the modulation of the c-MYC oncoprotein. PMID:27903583

  15. Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

    Science.gov (United States)

    Olivan, M.; Rigau, M.; Colás, E.; Garcia, M.; Montes, M.; Sequeiros, T.; Regis, L.; Celma, A.; Planas, J.; Placer, J.; Reventós, J.; de Torres, I.; Doll, A.; Morote, J.

    2015-01-01

    Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467–0.812), P < 0.001). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068–3.155), P = 0.028) or the combination of both drugs (OR: 3.059 (95% CI: 1.894–4.939), P < 0.001) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effects in vitro are enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence. PMID:25649906

  16. Reduced expression of α-L-Fucosidase-1 (FUCA-1) predicts recurrence and shorter cancer specific survival in luminal B LN+ breast cancer patients.

    Science.gov (United States)

    Bonin, Serena; Parascandolo, Alessia; Aversa, Cinzia; Barbazza, Renzo; Tsuchida, Nobuo; Castellone, Maria Domenica; Stanta, Giorgio; Vecchio, Giancarlo

    2018-03-16

    The lysosomal enzyme α-L-Fucosidase-1 (FUCA-1) catalyzes the hydrolytic cleavage of terminal fucose residues. FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors as its inactivation perturbs the fucosylation of proteins involved in cell adhesion, migration and metastases. Negativity to FUCA-1 was significantly related to the development of later recurrences in breast cancer patients with lymph node involvement at diagnosis. Cancer specific survival of luminal B LN+ patients was influenced by FUCA-1 expression as luminal B LN+ patients with positive expression had a longer cancer specific survival. FUCA-1 mRNA expression was inversely related to cancer stage and lymph node involvement. WB and qPCR analysis of FUCA-1 expression in breast cancer-derived cell lines confirmed an inverse relationship with tumor aggressiveness. This study shows that, within LN+ breast cancer patients, FUCA-1 is able to identify a sub-set of non recurrent patients characterized by the positive expression of FUCA-1 and that, within luminal B LN+ patients, the expression of FUCA-1 predicts longer cancer specific survival. We have analyzed FUCA-1 in 305 breast cancer patients by Immunohistochemistry (IHC), and by qPCR in breast cancer patients and in breast cancer cell lines.

  17. Sensitive detection of viral transcripts in human tumor transcriptomes.

    Directory of Open Access Journals (Sweden)

    Sven-Eric Schelhorn

    Full Text Available In excess of 12% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped 14 transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates

  18. MiR-133b is frequently decreased in gastric cancer and its overexpression reduces the metastatic potential of gastric cancer cells

    International Nuclear Information System (INIS)

    Zhao, Yu; Zhu, Zhenggang; Huang, Jie; Zhang, Li; Qu, Ying; Li, Jianfang; Yu, Beiqin; Yan, Min; Yu, Yingyan; Liu, Bingya

    2014-01-01

    Emerging evidence has shown that microRNAs are involved in gastric cancer development and progression. Here we examine the role of miR-133b in gastric cancer. Quantitative real-time PCR analysis was performed in 140 patient gastric cancer tissues and 8 gastric cancer cell lines. The effects of miR-133b in gastric cancer cells metastasis were examined by scratch assay, transwell migration and matrigel invasion. In vivo effects of miR-133b were examined in an intraperitoneal mouse tumor model. Targets of miR-133b were predicted by bioinformatics tools and validated by luciferase reporter analyses, western blot, and quantitative real-time PCR. MiR-133b was significantly downregulated in 70% (98/140) of gastric cancer patients. Expression of miR-133b was negatively correlated with lymph node metastasis of gastric cancer in patients. Similarly, the expression of miR-133b was significantly lower in seven tested gastric cancer cell lines than in the immortalized non-cancerous GES-1 gastric epithelial cells. Overexpression of miR-133b markedly inhibited metastasis of gastric cancer cells in vitro and in vivo. Moreover, the transcriptional factor Gli1 was identified as a direct target for miR-133b. Level of Gli1 protein but not mRNA was decreased by miR-133b. Activity of luciferase with Gli1 3′-untranslated region was markedly decreased by miR-133b in gastric cancer cells. Gli1 target genes, OPN and Zeb2, were also inhibited by miR133b. MiR-133b is frequently decreased in gastric cancer. Overexpression of miR-133b inhibits cell metastasis in vitro and in vivo partly by directly suppressing expression of Gli1 protein. These results suggested that miR-133b plays an important role in gastric cancer metastasis

  19. Expression of DIAPH1 is up-regulated in colorectal cancer and its down-regulation strongly reduces the metastatic capacity of colon carcinoma cells.

    Science.gov (United States)

    Lin, Yuan-Na; Izbicki, Jakob R; König, Alexandra; Habermann, Jens K; Blechner, Christine; Lange, Tobias; Schumacher, Udo; Windhorst, Sabine

    2014-04-01

    In most cases, metastatic colorectal cancer is not curable, thus new approaches are necessary to identify novel targets for colorectal cancer therapy. Actin-binding-proteins (ABPs) directly regulate motility of metastasising tumor cells, and for cortactin an association with colon cancer metastasis has been already shown. However, as its depletion only incompletely inhibits metastasis, additional, more suitable cellular targets have to be identified. Here we analyzed expression of the ABPs, DIAPH1, VASP, N-WASP, and fascin in comparison with cortactin and found that, besides cortactin, DIAPH1 was expressed with the highest frequency (63%) in colorectal cancer. As well as cortactin, DIAPH1 was not detectable in normal colon tissue and expression of both proteins was positively correlated with metastasis of colorectal cancer. To analyse the mechanistic role of DIAPH1 for metastasis of colon carcinoma cells in comparison with cortactin, expression of the proteins was stably down-regulated in the human colon carcinoma cell lines HT-29, HROC-24 and HCT-116. Analysis of metastasis of colon carcinoma cells in SCID mice revealed that depletion of DIAPH1 reduced metastasis 60-fold and depletion of cortactin 16-fold as compared with control cells. Most likely the stronger effect of DIAPH1 depletion on colon cancer metastasis is due to the fact that in vitro knock down of DIAPH1 impaired all steps of metastasis; adhesion, invasion and migration while down-regulation of cortactin only reduced adhesion and invasion. This very strong reducing effect of DIAPH1 depletion on colon carcinoma cell metastasis makes the protein a promising therapeutic target for individualized colorectal cancer therapy. © 2013 UICC.

  20. A phantom study on fetal dose reducing factors in pregnant patients with breast cancer during radiotherapy treatment

    Directory of Open Access Journals (Sweden)

    Akın Ogretici

    2017-01-01

    Full Text Available Purpose: This study aims to investigate the factors that reduce fetal dose in pregnant patients with breast cancer throughout their radiation treatment. Two main factors in a standard radiation oncology center are considered as the treatment planning systems (TPSs and simple shielding for intensity modulated radiation therapy technique. Materials and Methods: TPS factor was evaluated with two different planning algorithms: Anisotropic analytical algorithm and Acuros XB (external beam. To evaluate the shielding factor, a standard radiological purpose lead apron was chosen. For both studies, thermoluminescence dosimeters were used to measure the point dose, and an Alderson RANDO-phantom was used to simulate a female pregnant patient in this study. Thirteen measurement points were chosen in the 32nd slice of the phantom to cover all possible locations of a fetus up to 8th week of gestation. Results: The results show that both of the TPS algorithms are incapable of calculating the fetal doses, therefore, unable to reduce them at the planning stage. Shielding with a standard lead apron, however, showed a slight radiation protection (about 4.7% to the fetus decreasing the mean fetal dose from 84.8 mGy to 80.8 mGy, which cannot be disregarded in case of fetal irradiation. Conclusions: Using a lead apron for shielding the abdominal region of a pregnant patient during breast irradiation showed a minor advantage; however, its possible side effects (i.e., increased scattered radiation and skin dose should also be investigated further to solidify its benefits.

  1. Indocyanine Green-Loaded Polydopamine-Reduced Graphene Oxide Nanocomposites with Amplifying Photoacoustic and Photothermal Effects for Cancer Theranostics.

    Science.gov (United States)

    Hu, Dehong; Zhang, Jingnan; Gao, Guanhui; Sheng, Zonghai; Cui, Haodong; Cai, Lintao

    2016-01-01

    Photoacoustic (PA) imaging and photothermal therapy (PTT) as light-induced theranostic platforms have been attracted much attention in recent years. However, the development of highly efficient and integrated phototheranostic nanoagents for amplifying PA imaging and PTT treatments poses great challenges. Here, we report a novel phototheranostic nanoagent using indocyanine green-loaded polydopamine-reduced graphene oxide nanocomposites (ICG-PDA-rGO) with amplifying PA and PTT effects for cancer theranostics. The results demonstrate that the PDA layer coating on the surface of rGO could effectively absorb a large number of ICG molecules, quench ICG's fluorescence, and enhance the PDA-rGO's optical absorption at 780 nm. The obtained ICG-PDA-rGO exhibits stronger PTT effect and higher PA contrast than that of pure GO and PDA-rGO. After PA imaging-guided PTT treatments, the tumors in 4T1 breast subcutaneous and orthotopic mice models are suppressed completely and no treatment-induced toxicity being observed. It illustrates that the ICG-PDA-rGO nanocomposites constitute a new class of theranostic nanomedicine for amplifying PA imaging and PTT treatments.

  2. The Role of High-Density Lipoproteins in Reducing the Risk of Vascular Diseases, Neurogenerative Disorders, and Cancer

    Directory of Open Access Journals (Sweden)

    Donovan McGrowder

    2011-01-01

    Full Text Available High-density lipoprotein (HDL is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, as many physiological functions of HDL influence the cardiovascular system in favourable ways unless HDL is modified pathologically. The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from cardiovascular disease. Atheroprotective activities, as well as a functional deficiency of HDL, ultimately depend on the protein and lipid composition of HDL. Further, numerous epidemiological studies have shown a protective association between HDL-cholesterol and cognitive impairment. Oxidative stress, including lipid peroxidation, has been shown to be the mediator of the pathologic effects of numerous risk factors of Alzheimer's disease. Lifestyle interventions proven to increase HDL- cholesterol levels including “healthy” diet, regular exercise, weight control, and smoking cessation have also been shown to provide neuro-protective effects. This review will focus on current knowledge of the beneficial effects of HDL-cholesterol as it relates to cardiovascular diseases, breast and lung cancers, non-Hodgkin's lymphoma, as well as its neuroprotective potential in reducing the risk of Alzheimer's disease and dementia.

  3. Flaccidoxide-13-Acetate Extracted from the Soft Coral Cladiella kashmani Reduces Human Bladder Cancer Cell Migration and Invasion through Reducing Activation of the FAK/PI3K/AKT/mTOR Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Choo-Aun Neoh

    2017-12-01

    Full Text Available Metastasis of cancer is the cause of the majority of cancer deaths. Active compound flaccidoxide-13-acetate, isolated from the soft coral Cladiella kashmani, has been found to exhibit anti-tumor activity. In this study, Boyden chamber analysis, Western blotting and gelatin zymography assays indicated that flaccidoxide-13-acetate exerted inhibitory effects on the migration and invasion of RT4 and T24 human bladder cancer cells. The results demonstrated that flaccidoxide-13-acetate, in a concentration-dependent manner, reduced the levels of matrix metalloproteinase-2 (MMP-2, MMP-9, urokinase-type plasminogen activator receptor (uPAR, focal adhesion kinase (FAK, phosphatidylinositide-3 kinases (PI3K, p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR, p-mTOR, Ras homolog gene family, member A (Rho A, Ras, mitogen-activated protein kinase kinase 7 (MKK7 and mitogen-activated protein kinase kinase kinase 3 (MEKK3, and increased the expressions of tissue inhibitor of metalloproteinase-1 (TIMP-1 and TIMP-2 in RT4 and T24 cells. This study revealed that flaccidoxide-13-acetate suppressed cell migration and invasion by reducing the expressions of MMP-2 and MMP-9, regulated by the FAK/PI3K/AKT/mTOR pathway. In conclusion, our study was the first to demonstrate that flaccidoxide-13-acetate could be a potent medical agent for use in controlling the migration and invasion of bladder cancer.

  4. Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence.

    Science.gov (United States)

    Alsbeih, Ghazi A; Al-Harbi, Najla M; Bin Judia, Sara S; Khoja, Hatim A; Shoukri, Mohamed M; Tulbah, Asma M

    2017-07-01

    Cervical cancer is a predominantly human papillomavirus (HPV)-driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence. Patients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples. The incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV-positive and 16 HPV genotypes were detected-mostly genotypes 16 (75%) and 18 (9%)-with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36-0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P Cervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459-66. © 2017 American Cancer Society. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  5. Comparative transcriptomics in the Triticeae

    Directory of Open Access Journals (Sweden)

    Waugh Robbie

    2009-06-01

    Full Text Available Abstract Background Barley and particularly wheat are two grass species of immense agricultural importance. In spite of polyploidization events within the latter, studies have shown that genotypically and phenotypically these species are very closely related and, indeed, fertile hybrids can be created by interbreeding. The advent of two genome-scale Affymetrix GeneChips now allows studies of the comparison of their transcriptomes. Results We have used the Wheat GeneChip to create a "gene expression atlas" for the wheat transcriptome (cv. Chinese Spring. For this, we chose mRNA from a range of tissues and developmental stages closely mirroring a comparable study carried out for barley (cv. Morex using the Barley1 GeneChip. This, together with large-scale clustering of the probesets from the two GeneChips into "homologous groups", has allowed us to perform a genomic-scale comparative study of expression patterns in these two species. We explore the influence of the polyploidy of wheat on the results obtained with the Wheat GeneChip and quantify the correlation between conservation in gene sequence and gene expression in wheat and barley. In addition, we show how the conservation of expression patterns can be used to elucidate, probeset by probeset, the reliability of the Wheat GeneChip. Conclusion While there are many differences in expression on the level of individual genes and tissues, we demonstrate that the wheat and barley transcriptomes appear highly correlated. This finding is significant not only because given small evolutionary distance between the two species it is widely expected, but also because it demonstrates that it is possible to use the two GeneChips for comparative studies. This is the case even though their probeset composition reflects rather different design principles as well as, of course, the present incomplete knowledge of the gene content of the two species. We also show that, in general, the Wheat GeneChip is not able

  6. Identification of Reprogrammed Myeloid Cell Transcriptomes in NSCLC.

    Directory of Open Access Journals (Sweden)

    Anna Durrans

    Full Text Available Lung cancer is the leading cause of cancer related mortality worldwide, with non-small cell lung cancer (NSCLC as the most prevalent form. Despite advances in treatment options including minimally invasive surgery, CT-guided radiation, novel chemotherapeutic regimens, and targeted therapeutics, prognosis remains dismal. Therefore, further molecular analysis of NSCLC is necessary to identify novel molecular targets that impact prognosis and the design of new-targeted therapies. In recent years, tumor "activated/reprogrammed" stromal cells that promote carcinogenesis have emerged as potential therapeutic targets. However, the contribution of stromal cells to NSCLC is poorly understood. Here, we show increased numbers of bone marrow (BM-derived hematopoietic cells in the tumor parenchyma of NSCLC patients compared with matched adjacent non-neoplastic lung tissue. By sorting specific cellular fractions from lung cancer patients, we compared the transcriptomes of intratumoral myeloid compartments within the tumor bed with their counterparts within adjacent non-neoplastic tissue from NSCLC patients. The RNA sequencing of specific myeloid compartments (immature monocytic myeloid cells and polymorphonuclear neutrophils identified differentially regulated genes and mRNA isoforms, which were inconspicuous in whole tumor analysis. Genes encoding secreted factors, including osteopontin (OPN, chemokine (C-C motif ligand 7 (CCL7 and thrombospondin 1 (TSP1 were identified, which enhanced tumorigenic properties of lung cancer cells indicative of their potential as targets for therapy. This study demonstrates that analysis of homogeneous stromal populations isolated directly from fresh clinical specimens can detect important stromal genes of therapeutic value.

  7. Methods for Reducing Normal Tissue Complication Probabilities in Oropharyngeal Cancer: Dose Reduction or Planning Target Volume Elimination

    Energy Technology Data Exchange (ETDEWEB)

    Samuels, Stuart E.; Eisbruch, Avraham; Vineberg, Karen; Lee, Jae; Lee, Choonik; Matuszak, Martha M.; Ten Haken, Randall K.; Brock, Kristy K., E-mail: kbrock@med.umich.edu

    2016-11-01

    Purpose: Strategies to reduce the toxicities of head and neck radiation (ie, dysphagia [difficulty swallowing] and xerostomia [dry mouth]) are currently underway. However, the predicted benefit of dose and planning target volume (PTV) reduction strategies is unknown. The purpose of the present study was to compare the normal tissue complication probabilities (NTCP) for swallowing and salivary structures in standard plans (70 Gy [P70]), dose-reduced plans (60 Gy [P60]), and plans eliminating the PTV margin. Methods and Materials: A total of 38 oropharyngeal cancer (OPC) plans were analyzed. Standard organ-sparing volumetric modulated arc therapy plans (P70) were created and then modified by eliminating the PTVs and treating the clinical tumor volumes (CTVs) only (C70) or maintaining the PTV but reducing the dose to 60 Gy (P60). NTCP dose models for the pharyngeal constrictors, glottis/supraglottic larynx, parotid glands (PGs), and submandibular glands (SMGs) were analyzed. The minimal clinically important benefit was defined as a mean change in NTCP of >5%. The P70 NTCP thresholds and overlap percentages of the organs at risk with the PTVs (56-59 Gy, vPTV{sub 56}) were evaluated to identify the predictors for NTCP improvement. Results: With the P60 plans, only the ipsilateral PG (iPG) benefited (23.9% vs 16.2%; P<.01). With the C70 plans, only the iPG (23.9% vs 17.5%; P<.01) and contralateral SMG (cSMG) (NTCP 32.1% vs 22.9%; P<.01) benefited. An iPG NTCP threshold of 20% and 30% predicted NTCP benefits for the P60 and C70 plans, respectively (P<.001). A cSMG NTCP threshold of 30% predicted for an NTCP benefit with the C70 plans (P<.001). Furthermore, for the iPG, a vPTV{sub 56} >13% predicted benefit with P60 (P<.001) and C70 (P=.002). For the cSMG, a vPTV{sub 56} >22% predicted benefit with C70 (P<.01). Conclusions: PTV elimination and dose-reduction lowered the NTCP of the iPG, and PTV elimination lowered the NTCP of the cSMG. NTCP thresholds and the

  8. Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance.

    Science.gov (United States)

    Tian, Mengqian; Chen, Ruoyu; Li, Tianwen; Xiao, Bingxiu

    2018-03-01

    Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases including cancers. However, little is known about circRNAs' diagnostic values for gastric cancer, one of the worldwide most common diseases of mortality. The hsa_circ_0003159 levels in 108 paired gastric cancer tissues and adjacent non-tumorous tissues from surgical patients with gastric cancer were first detected by real-time quantitative reverse transcription-polymerase chain reaction. Then, the relationships between hsa_circ_0003159 expression levels in gastric cancer tissues and the clinicopathological factors of patients with gastric cancer were analyzed. Finally, its diagnostic value was evaluated through the receiver operating characteristic curve. Compared with paired adjacent non-tumorous tissues, hsa_circ_0003159 expression was significantly down-regulated in gastric cancer tissues. What is more, we found that hsa_circ_0003159 expression levels were significantly negatively associated with gender, distal metastasis, and tumor-node-metastasis stage. All of the results suggest that hsa_circ_0003159 may be a potential cancer marker of patients with gastric cancer. © 2017 Wiley Periodicals, Inc.

  9. Reducing Xerostomia After Chemo-IMRT for Head-and-Neck Cancer: Beyond Sparing the Parotid Glands

    Energy Technology Data Exchange (ETDEWEB)

    Little, Michael [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States); Cancer Center Biostatistics Core, University of Michigan, Ann Arbor, MI (United States); Feng, Felix Y.; Vineberg, Karen [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States); Cornwall, Craig; Murdoch-Kinch, Carol-Anne [Hospital Dentistry, University of Michigan, Ann Arbor, MI (United States); Eisbruch, Avraham, E-mail: eisbruch@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, MI (United States)

    2012-07-01

    Purpose: To assess whether, in addition to sparing the parotid glands (PGs), xerostomia after chemotherapy plus intensity-modulated radiotherapy (chemo-IMRT) for head-and-neck cancer is affected by reducing the dose to the other salivary glands. Patients and Methods: In a prospective study, 78 patients with Stage III-IV oropharynx/nasopharynx cancer underwent chemo-IMRT, with the aim of sparing the parts of the bilateral PGs, oral cavity (OC) containing the minor salivary glands, and contralateral submandibular gland (SMG) outside the target (when contralateral level I was not a target). Before therapy and periodically for 24 months, validated patient-reported xerostomia questionnaire (XQ) scores and observer-graded xerostomia scores were recorded. Also, the stimulated and unstimulated saliva was measured selectively from each of the PGs and SMGs. The mean OC doses served as surrogates of minor salivary gland dysfunction. Regression models assessed the XQ and observer-graded xerostomia predictors. Results: Statistically significant predictors of the XQ score on univariate analysis included the OC, PG, and SMG mean doses and the baseline XQ score, time since RT, and both stimulated and unstimulated PG saliva flow rates. Similar factors were statistically significant predictors of observer-graded xerostomia. The OC, PG, and SMG mean doses were moderately intercorrelated (r = 0.47-0.55). On multivariate analyses, after adjusting for the PG and SMG doses, the OC mean dose (p < .0001), interval from RT (p < .0001), and stimulated PG saliva (p < .0025) were significant predictors of the XQ scores and the OC mean dose and time for observer-graded xerostomia. Although scatter plots showed no thresholds, an OC mean dose of <40 Gy and contralateral SMG mean dose of <50 Gy were each associated with low patient-reported and observer-rated xerostomia at almost all post-therapy points. Conclusion: The PG, SMG, and OC mean doses were significant predictors of both patient

  10. Reducing Xerostomia After Chemo-IMRT for Head-and-Neck Cancer: Beyond Sparing the Parotid Glands

    International Nuclear Information System (INIS)

    Little, Michael; Schipper, Matthew; Feng, Felix Y.; Vineberg, Karen; Cornwall, Craig; Murdoch-Kinch, Carol-Anne; Eisbruch, Avraham

    2012-01-01

    Purpose: To assess whether, in addition to sparing the parotid glands (PGs), xerostomia after chemotherapy plus intensity-modulated radiotherapy (chemo-IMRT) for head-and-neck cancer is affected by reducing the dose to the other salivary glands. Patients and Methods: In a prospective study, 78 patients with Stage III-IV oropharynx/nasopharynx cancer underwent chemo-IMRT, with the aim of sparing the parts of the bilateral PGs, oral cavity (OC) containing the minor salivary glands, and contralateral submandibular gland (SMG) outside the target (when contralateral level I was not a target). Before therapy and periodically for 24 months, validated patient-reported xerostomia questionnaire (XQ) scores and observer-graded xerostomia scores were recorded. Also, the stimulated and unstimulated saliva was measured selectively from each of the PGs and SMGs. The mean OC doses served as surrogates of minor salivary gland dysfunction. Regression models assessed the XQ and observer-graded xerostomia predictors. Results: Statistically significant predictors of the XQ score on univariate analysis included the OC, PG, and SMG mean doses and the baseline XQ score, time since RT, and both stimulated and unstimulated PG saliva flow rates. Similar factors were statistically significant predictors of observer-graded xerostomia. The OC, PG, and SMG mean doses were moderately intercorrelated (r = 0.47–0.55). On multivariate analyses, after adjusting for the PG and SMG doses, the OC mean dose (p < .0001), interval from RT (p < .0001), and stimulated PG saliva (p < .0025) were significant predictors of the XQ scores and the OC mean dose and time for observer-graded xerostomia. Although scatter plots showed no thresholds, an OC mean dose of <40 Gy and contralateral SMG mean dose of <50 Gy were each associated with low patient-reported and observer-rated xerostomia at almost all post-therapy points. Conclusion: The PG, SMG, and OC mean doses were significant predictors of both patient

  11. Characterizing the transcriptome and molecular markers information ...

    Indian Academy of Sciences (India)

    2008). Analyses of the genetic structure .... The annotations and classifications for the transcriptome ... Based on the Pfam classification, the predic- ..... J. Lipid. Res. 33, 251–262. Eckert C. G., Samis K. E. and Lougheed S. C. 2008 Genetic vari-.

  12. The floral transcriptome of Eucalyptus grandis

    CSIR Research Space (South Africa)

    Vining, KJ

    2015-10-01

    Full Text Available As a step toward functional annotation of genes required for floral initiation and development within the Eucalyptus genome, we used short read sequencing to analyze transcriptomes of floral buds from early and late developmental stages...

  13. Fentanyl induces autophagy via activation of the ROS/MAPK pathway and reduces the sensitivity of cisplatin in lung cancer cells.

    Science.gov (United States)

    Yao, Jiaqi; Ma, Chi; Gao, Wei; Liang, Jinxiao; Liu, Chang; Yang, Hongfang; Yan, Qiu; Wen, Qingping

    2016-12-01

    Cancer pain is the most common complication of lung carcinoma. Opioid agonist fentanyl is widely used for relieving pain in cancer patients, and cisplatin (DDP)‑based chemotherapy is commonly used for the treatment of advanced lung cancer; these two drugs are always used together in lung carcinoma patients. However, the mechanisms and related biological pathways by which fentanyl influences cisplatin sensitivity are relatively poorly reported. Here, we found that fentanyl reduces the sensitivity of cisplatin in human lung cancer cells and induces autophagy. Fentanyl induced reactive oxygen species (ROS) generation and JNK activation. N-acetyl‑L‑cysteine is a ROS scavenger and antioxidant, and the inhibition of JNK with SP600125 prevented fentanyl‑induced autophagy. We also found that 3-methyladenine (3-MA; an autophagy inhibitor) increased the sensitivity of DDP and weakened the inhibition of fentanyl. In conclusion, fentanyl reduces the sensitivity of cisplatin in lung cancer cells through the ROS-JNK-autophagy pathway, whereas the autophagy inhibitor 3-MA may weaken this effect.

  14. The REDUCE metagram: a comprehensive prediction tool for determining the utility of dutasteride chemoprevention in men at risk for prostate cancer

    Directory of Open Access Journals (Sweden)

    Carvell eNguyen

    2012-10-01

    Full Text Available Introduction: 5-alpha reductase inhibitors can reduce the risk of prostate cancer but can be associated with significant side effects. A library of nomograms which predict the risk of clinical endpoints relevant to dutasteride treatment may help determine if chemoprevention is suited to the individual patient. Methods: Data from the REDUCE trial was used to identify predictive factors for nine endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biopsy cohort, Cox proportional hazards and competing risks regression models were used to build 18 nomograms, whose predictive ability was measured by concordance index and calibration plots. Results: A total of 18 nomograms assessing the risks of cancer, high-grade cancer, high grade prostatic intraepithelial neoplasia (HGPIN, atypical small acinar proliferation (ASAP, erectile dysfunction (ED, acute urinary retention (AUR, gynecomastia, urinary tract infection (UTI and BPH-related surgery either on or off dutasteride were created. The nomograms for cancer, high grade cancer, ED, AUR, and BPH-related surgery demonstrated good discrimination and calibration while those for gynecomastia, UTI, HGPIN, and ASAP predicted no better than random chance. Conclusions: To aid patients in determining whether the benefits of dutasteride use outweigh the risks, we have developed a comprehensive metagram that can generate individualized risks of 9 outcomes relevant to men considering chemoprevention. Better models based on more predictive markers are needed for some of the endpoints but the current metagram demonstrates potential as a tool for patient counseling and decision making that is accessible, intuitive, and clinically relevant.

  15. Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway

    NARCIS (Netherlands)

    Kodach, L.L.; Jacobs, R.J.; Voorneveld, P.W.; Wildenberg, M.E.; Verspaget, H.W.; van Wezel, T.; Morreau, H.; Hommes, D.W.; Peppelenbosch, M.P.; van den Brink, G.R.; Hardwick, J.C.H.

    2011-01-01

    Promoter hypermethylation is an important and potentially reversible mechanism of tumour suppressor gene silencing in cancer. Compounds that demethylate tumour suppressor genes and induce differentiation of cancer cells, but do not have toxic side effects, would represent an exciting option in

  16. 3rd International Conference on Transcriptomics

    OpenAIRE

    John A Daniel

    2017-01-01

    Conference Series has been instrumental in conducting international Biochemistry meetings for seven years, and very excited to expand Europe, America and Asia Pacific continents. Previous meetings were held in major cities like Philadelphia, Orlando with success the meetings again scheduled in three continents. 3rd International Conference on Transcriptomics to be held during October 30 - November 01, 2017 at Bangkok, Thailand The Global Transcriptomics business sector to develop at a C...

  17. Familial diabetes is associated with reduced risk of cancer in diabetic patients: a possible role for metformin.

    Science.gov (United States)

    Berstein, Lev M; Boyarkina, Marina P; Teslenko, Svetlana Yu

    2012-06-01

    Type 2 diabetes mellitus (DM2) is a risk factor of a number of malignancies. Therefore, it is important to identify factors linking DM2 and cancer within family units and how current treatment regimens influence the development of cancer in DM2 patients. The present case-controlled study was designed to assess DM2 prevalence among parents or siblings of (a) cancer patients who did not have diabetes (n = 77; age 59.3 ± 1.3 years) or (b) had overt (n = 197; 63.7 ± 0.6 years) or latent (n = 25; 61.5 ± 1.5 years) DM2 and (c) of female DM2 patients without cancer (n = 172; 61.7 ± 0.6 years). In the families of cancer-free DM2 women, DM2 was found to be significantly more frequent (30.8 ± 3.5%) than in families of cancer patients without diabetes (in all patients: 6.5 ± 2.8%; in female patients: 5.0 ± 3.4%). More importantly, DM2 in families of cancer-free DM2 women was more frequent than in the families of DM2 patients having mammary (9.5 ± 4.5%), endometrial (6.3 ± 4.1%) or any other cancer (in all: 15.2 ± 2.6%; in women: 12.9 ± 2.8%). Additionally, DM2 patients without cancer, who had parents or siblings with DM2, received biguanide metformin versus sulfonylurea derivatives more often than those with breast or endometrial cancer, either with or without family history of DM2. Our data indicate that familial DM2 may have a protective effect for some cancer types and that the type of anti-diabetes therapy may be a factor of influence in the associations observed.

  18. Sexuality and quality of life in women with a prior diagnosis of breast cancer after risk-reducing salpingo-oophorectomy.

    Science.gov (United States)

    Tucker, Paige E; Saunders, Christobel; Bulsara, Max K; Tan, Jason Jit-Sun; Salfinger, Stuart G; Green, Helena; Cohen, Paul A

    2016-12-01

    To investigate the prevalence of sexual dysfunction in women with a history of breast cancer following risk-reducing salpingo-oophorectomy (RRSO). A secondary objective was to examine the effect of a prior diagnosis of breast cancer, and other factors, on sexuality and quality of life (QoL) outcomes. Cross-sectional study of 119 women who underwent RRSO between 2009 and 2014. Data were collected via a questionnaire comprising demographic information and validated measures of sexual function, sexual distress, relationship satisfaction, body image, psychological stress, menopause symptoms and general quality of life. Sixty out of 119 participants who underwent RRSO had a history of breast cancer. Eighty percent of women with breast cancer had female sexual dysfunction (FSD) and 82% had hypoactive sexual desire disorder (HSDD) after RRSO. Bilateral mastectomy was associated with higher rates of HSDD (p = 0.028) and higher body image self-consciousness (BISC) during sexual activity (p = 0.011). Breast reconstruction was associated with higher relationship satisfaction (RAS) scores (p = 0.004). Compared to Tamoxifen, aromatase inhibitors (AI) were significantly associated with reduced lubrication (p = 0.041), arousal (p = 0.004), orgasm (p = 0.002) and greater dyspareunia (p = 0.027). Prior diagnosis of breast cancer was not associated with the prevalence of FSD (p = 0.532). High rates of FSD and HSDD occur in women with breast cancer following RRSO. Low relationship satisfaction, bodily pain, bilateral mastectomy and the use of aromatase inhibitors were associated with poorer sexual function. Women had similar sexual outcomes and QoL after RRSO, regardless of breast cancer history. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Silencing of NRF2 Reduces the Expression of ALDH1A1 and ALDH3A1 and Sensitizes to 5-FU in Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hong-Quan Duong

    2017-07-01

    Full Text Available Pancreatic cancer remains an intractable cancer with a poor five-year survival rate, which requires new therapeutic modalities based on the biology of pancreatic oncogenesis. Nuclear factor E2 related factor-2 (NRF2, a key cytoprotective nuclear transcription factor, regulates antioxidant production, reduction, detoxification and drug efflux proteins. It also plays an essential role in cell homeostasis, cell proliferation and resistance to chemotherapy. We aimed to evaluate the possibility that modulation of NRF2 expression could be effective in the treatment of pancreatic cancer cells. We investigated whether the depletion of NRF2 by using small interfering RNAs (siRNAs is effective in the expression of biomarkers of pancreatic cancer stemness such as aldehyde dehydrogenase 1 family, member A1 (ALDH1A1 and aldehyde dehydrogenase 3 family, member A1 (ALDH3A1. NRF2 knockdown markedly reduced the expression of NRF2 and glutamate-cysteine ligase catalytic subunit (GCLC in cell lines established from pancreatic cancers. NRF2 silencing also decreased the ALDH1A1 and ALDH3A1 expression. Furthermore, this NRF2 depletion enhanced the antiproliferative effects of the chemotherapeutic agent, 5-fluorouracil (5-FU in pancreatic cancer cells.

  20. Transcriptomic Response of Chinese Yew (Taxus chinensis to Cold Stress

    Directory of Open Access Journals (Sweden)

    Xianghua Yu

    2017-04-01

    Full Text Available Taxus chinensis is a rare and endangered shrub, highly sensitive to temperature changes and widely known for its potential in cancer treatment. How gene expression of T. chinensis responds to low temperature is still unknown. To investigate cold response of the genus Taxus, we obtained the transcriptome profiles of T. chinensis grown under normal and low temperature (cold stress, 0°C conditions using Illumina Miseq sequencing. A transcriptome including 83,963 transcripts and 62,654 genes were assembled from 4.16 Gb of reads data. Comparative transcriptomic analysis identified 2,025 differently expressed (DE isoforms at p < 0.05, of which 1,437 were up-regulated by cold stress and 588 were down-regulated. Annotation of DE isoforms indicated that transcription factors (TFs in the MAPK signaling pathway and TF families of NAC, WRKY, bZIP, MYB, and ERF were transcriptionally activated. This might have been caused by the accumulation of secondary messengers, such as reactive oxygen species (ROS and Ca2+. While accumulation of ROS will have caused damages to cells, our results indicated that to adapt to low temperatures T. chinensis employed a series of mechanisms to minimize these damages. The mechanisms included: (i cold-enhanced expression of ROS deoxidant systems, such as peroxidase and phospholipid hydroperoxide glutathione peroxidase, to remove ROS. This was further confirmed by analyses showing increased activity of POD, SOD, and CAT under cold stress. (ii Activation of starch and sucrose metabolism, thiamine metabolism, and purine metabolism by cold-stress to produce metabolites which either protect cell organelles or lower the ROS content in cells. These processes are regulated by ROS signaling, as the “feedback” toward ROS accumulation.

  1. Integrative investigation of metabolic and transcriptomic data

    Directory of Open Access Journals (Sweden)

    Önsan Z İlsen

    2006-04-01

    Full Text Available Abstract Background New analysis methods are being developed to integrate data from transcriptome, proteome, interactome, metabolome, and other investigative approaches. At the same time, existing methods are being modified to serve the objectives of systems biology and permit the interpretation of the huge datasets currently being generated by high-throughput methods. Results Transcriptomic and metabolic data from chemostat fermentors were collected with the aim of investigating the relationship between these two data sets. The variation in transcriptome data in response to three physiological or genetic perturbations (medium composition, growth rate, and specific gene deletions was investigated using linear modelling, and open reading-frames (ORFs whose expression changed significantly in response to these perturbations were identified. Assuming that the metabolic profile is a function of the transcriptome profile, expression levels of the different ORFs were used to model the metabolic variables via Partial Least Squares (Projection to Latent Structures – PLS using PLS toolbox in Matlab. Conclusion The experimental design allowed the analyses to discriminate between the effects which the growth medium, dilution rate, and the deletion of specific genes had on the transcriptome and metabolite profiles. Metabolite data were modelled as a function of the transcriptome to determine their congruence. The genes that are involved in central carbon metabolism of yeast cells were found to be the ORFs with the most significant contribution to the model.

  2. Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets.

    Science.gov (United States)

    Thomson, Cynthia A; Stopeck, Alison T; Bea, Jennifer W; Cussler, Ellen; Nardi, Emily; Frey, Georgette; Thompson, Patricia A

    2010-01-01

    Overweight status is common among women breast cancer survivors and places them at greater risk for metabolic disorders, cardiovascular morbidity, and breast cancer recurrence than nonoverweight survivors. Efforts to promote weight control in this population are needed. The objective of this research was to evaluate the effect of low-fat or low-carbohydrate diet counseling on weight loss, body composition, and changes in metabolic indexes in overweight postmenopausal breast cancer survivors. Survivors (n = 40) were randomized to receive dietitian counseling for a low-fat or a reduced carbohydrate diet for 6 mo. Weight and metabolic measures, including glucose, insulin, HbA1c, HOMA, lipids, hsCRP, as well as blood pressure were measured at baseline, 6, 12 and 24 wk. Dietary intake of fat and carbohydrate was reduced by 24 and 76 g/day, respectively. Weight loss averaged 6.1 (± 4.8 kg) at 24 wk and was not significantly different by diet group; loss of lean mass was also demonstrated. All subjects demonstrated improvements in total/HDL cholesterol ratio, and significant reductions in HbA1c, insulin, and HOMA. Triglycerides levels were significantly reduced only in the low-carbohydrate diet group (-31.1 ± 36.6; P = 0.01). Significant improvements in weight and metabolic indexes can be demonstrated among overweight breast cancer survivors adherent to either a carbohydrate- or fat-restricted diet.

  3. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

    Science.gov (United States)

    Greco, Stephanie H; Tomkötter, Lena; Vahle, Anne-Kristin; Rokosh, Rae; Avanzi, Antonina; Mahmood, Syed Kashif; Deutsch, Michael; Alothman, Sara; Alqunaibit, Dalia; Ochi, Atsuo; Zambirinis, Constantinos; Mohaimin, Tasnima; Rendon, Mauricio; Levie, Elliot; Pansari, Mridul; Torres-Hernandez, Alejandro; Daley, Donnele; Barilla, Rocky; Pachter, H Leon; Tippens, Daniel; Malik, Hassan; Boutajangout, Allal; Wisniewski, Thomas; Miller, George

    2015-01-01

    Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.

  4. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

    Directory of Open Access Journals (Sweden)

    Stephanie H Greco

    Full Text Available Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.

  5. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia

    Science.gov (United States)

    Rokosh, Rae; Avanzi, Antonina; Mahmood, Syed Kashif; Deutsch, Michael; Alothman, Sara; Alqunaibit, Dalia; Ochi, Atsuo; Zambirinis, Constantinos; Mohaimin, Tasnima; Rendon, Mauricio; Levie, Elliot; Pansari, Mridul; Torres-Hernandez, Alejandro; Daley, Donnele; Barilla, Rocky; Pachter, H. Leon; Tippens, Daniel; Malik, Hassan; Boutajangout, Allal; Wisniewski, Thomas; Miller, George

    2015-01-01

    Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-β) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-β inhibition using the anti-TGF-β antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-β inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival. PMID:26172047

  6. Immediate treatment with bicalutamide 150mg as adjuvant therapy significantly reduces the risk of PSA progression in early prostate cancer

    DEFF Research Database (Denmark)

    See, W; Iversen, P; Wirth, M

    2003-01-01

    To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer.......To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer....

  7. Adjustment of Serum HE4 to reduced Glomerular filtration and its use in Biomarker-based prediction of deep Myometrial invasion in endometrial cancer

    DEFF Research Database (Denmark)

    Chovanec, Josef; Selingerova, Iveta; Greplova, Kristina

    2017-01-01

    Background: We investigated the efficacy of circulating biomarkers together with histological grade and age to predict deep myometrial invasion (dMI) in endometrial cancer patients. Methods: HE4ren was developed adjusting HE4 serum levels towards decreased glomerular filtration rate as quantified...... levels to reduced eGFR that enables quantification of time-dependent changes in HE4 production and elimination irrespective of age and renal function in women. Utilizing HE4ren improves performance of biomarker-based models for prediction of dMI in endometrial cancer patients....

  8. Target tailoring and proton beam therapy to reduce small bowel dose in cervical cancer radiotherapy. A comparison of benefits

    Energy Technology Data Exchange (ETDEWEB)

    Boer, Peter de; Westerveld, Henrike; Smit, Mark; Bel, Arjan; Rasch, Coen R.N.; Stalpers, Lukas J.A. [Academic Medical Center, University of Amsterdam, Department of Radiation Oncology, Amsterdam (Netherlands); Schoot, Agustinus J.A.J. van de [The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Radiation Oncology, Amsterdam (Netherlands); Buist, Marrije R. [Academic Medical Center, University of Amsterdam, Department of Gynaecology and Obstetrics, Amsterdam (Netherlands)

    2018-03-15

    The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT). The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V{sub 15Gy}, V{sub 30Gy}, V{sub 45Gy} and D{sub mean} for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for ≥grade 2 acute small bowel toxicity was calculated. Both IMPT and MRI-based target tailoring resulted in significant reductions in V{sub 15Gy}, V{sub 30Gy}, V{sub 45Gy} and D{sub mean} for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of >10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This >10% NTCP reduction was expected if the V{sub 45Gy} for bowel bag was >275 cm{sup 3} and >200 cm{sup 3}, respectively, during standard IGART alone. In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity. (orig.) [German] In der vorliegenden Studie wurden die moeglichen klinischen Vorteile einer Zielvolumenpraezisierung durch Ausschluss des tumorfreien proximalen Gebaermutteranteils bei der ''image-guided adaptive radiotherapy

  9. Functional inhibition of Ubiquitin conjugating Enzyme (UBE2C) reduces proliferation and sensitizes cervical and breast cancer cells to radiation, doxorubicin, tamoxifen and letrozole

    International Nuclear Information System (INIS)

    Bose, Mayil Vahanan; Rawat, Akhilesh; Gopisetty, Gopal; Thangarajan, Rajkumar; Ganesharaja, Selvaluxmy

    2014-01-01

    Cervical cancer is the second most common cancer in women, worldwide. About 80% of cervical cancer cases occur in developing countries. Breast cancer has overtaken cervical cancer in most of the urban centers in India. In recent years, interest in the role of Ubiquitin conjugating Enzyme E2C (UBE2C) in cancer has shown a dramatic increase. Several studies have reported UBE2C as a potential oncogene and therapeutic target. The objective of the study was to elucidate radiation and chemo-sensitivity in response to functional inhibition of UBE2C in cervical and breast cancer cell lines. Taqman Real time PCR was performed to measure UBE2C levels in cervical and breast cancer cell lines. A dominant negative form of UBE2C (DN-UBE2C) was used to functionally inhibit wild type UBE2C. Cell proliferation and anchorage independent growth were measured by colorimetric assay and soft agar assay respectively. Radiation and chemo response of cell lines were assessed by colorimetric assay and clonogenic assay. Difference in sensitivity to radiation was observed among the cervical cancer cell lines studied. The growth rate of SiHa and HeLa transfected with DN- UBE2C was significantly reduced compared to vector control. Further, DN-UBE2C mediated radio-sensitivity was correlated with a significant decrease in resistance to radiation by SiHa and HeLa cells after transfection when compared to control cultures. Similarly, both the growth rate and the anchorage independent growth of MCF7 and MDAMB231 cells transfected with DN-UBE2C were significantly reduced compared to cells transfected with vector alone. MCF7 and MDAMB231 cells expressing DN-UBE2C were significantly more sensitive to different doses of radiation and doxorubicin compared to controls. In addition, DN-UBE2C transfected MCF7 cells were more sensitive to inhibition by tamoxifen and letrozole compared to vector controls. These results suggest that UBE2C can be used as a potential therapeutic target for cervical and breast

  10. Targeting Human Papillomavirus to Reduce the Burden of Cervical, Vulvar and Vaginal Cancer and Pre-Invasive Neoplasia

    DEFF Research Database (Denmark)

    Nygard, Mari; Hansen, Bo Terning; Dillner, Joakim

    2014-01-01

    BACKGROUND: Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination...... with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004-2006, prior to the availability of HPV vaccines, in order...... to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases. METHODS: Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias...

  11. ONC201 Targets AR and AR-V7 Signaling, Reduces PSA, and Synergizes with Everolimus in Prostate Cancer.

    Science.gov (United States)

    Lev, Avital; Lulla, Amriti R; Ross, Brian C; Ralff, Marie D; Makhov, Petr B; Dicker, David T; El-Deiry, Wafik S

    2018-05-01

    Androgen receptor (AR) signaling plays a key role in prostate cancer progression, and androgen deprivation therapy (ADT) is a mainstay clinical treatment regimen for patients with advanced disease. Unfortunately, most prostate cancers eventually become androgen-independent and resistant to ADT with patients progressing to metastatic castration-resistant prostate cancer (mCRPC). Constitutively activated AR variants (AR-V) have emerged as mediators of resistance to AR-targeted therapy and the progression of mCRPC, and they represent an important therapeutic target. Out of at least 15 AR-Vs described thus far, AR-V7 is the most abundant, and its expression correlates with ADT resistance. ONC201/TIC10 is the founding member of the imipridone class of small molecules and has shown anticancer activity in a broad range of tumor types. ONC201 is currently being tested in phase I/II clinical trials for advanced solid tumors, including mCRPC, and hematologic malignancies. There has been promising activity observed in patients in early clinical testing. This study demonstrates preclinical single-agent efficacy of ONC201 using in vitro and in vivo models of prostate cancer. ONC201 has potent antiproliferative and proapoptotic effects in both castration-resistant and -sensitive prostate cancer cells. Furthermore, the data demonstrate that ONC201 downregulates the expression of key drivers of prostate cancer such as AR-V7 and downstream target genes including the clinically used biomarker PSA (KLK3). Finally, the data also provide a preclinical rationale for combination of ONC201 with approved therapeutics for prostate cancer such as enzalutamide, everolimus (mTOR inhibitor), or docetaxel. Implications: The preclinical efficacy of ONC201 as a single agent or in combination, in hormone-sensitive or castration-resistant prostate cancer, suggests the potential for immediate clinical translation. Mol Cancer Res; 16(5); 754-66. ©2018 AACR . ©2018 American Association for Cancer

  12. Unique transcriptomic response to sepsis is observed among patients of different age groups.

    Science.gov (United States)

    Raymond, Steven L; López, María Cecilia; Baker, Henry V; Larson, Shawn D; Efron, Philip A; Sweeney, Timothy E; Khatri, Purvesh; Moldawer, Lyle L; Wynn, James L

    2017-01-01

    Sepsis is a major cause of morbidity and mortality, especially at the extremes of age. To understand the human age-specific transcriptomic response to sepsis, a multi-cohort, pooled analysis was conducted on adults, children, infants, and neonates with and without sepsis. Nine public whole-blood gene expression datasets (636 patients) were employed. Age impacted the transcriptomic host response to sepsis. Gene expression from septic neonates and adults was more dissimilar whereas infants and children were more similar. Neonates showed reductions in inflammatory recognition and signaling pathways compared to all other age groups. Likewise, adults demonstrated decreased pathogen sensing, inflammation, and myeloid cell function, as compared to children. This may help to explain the increased incidence of sepsis-related organ failure and death in adults. The number of dysregulated genes in septic patients was proportional to age and significantly differed among septic adults, children, infants, and neonates. Overall, children manifested a greater transcriptomic intensity to sepsis as compared to the other age groups. The transcriptomic magnitude for adults and neonates was dramatically reduced as compared to children and infants. These findings suggest that the transcriptomic response to sepsis is age-dependent, and diagnostic and therapeutic efforts to identify and treat sepsis will have to consider age as an important variable.

  13. Employing the church as a marketer of cancer prevention: a look at a health promotion project aimed to reduce colorectal cancer among African Americans in the Midwest.

    Science.gov (United States)

    Lumpkins, Crystal Y; Coffey, Candice R; Daley, Christine M; Greiner, K Allen

    2013-01-01

    Health promotion programs designed to address colorectal cancer disparities among African Americans are increasing. Unfortunately, this group still shoulders a disproportionate mortality burden in the United States; these numbers are also reflective of colorectal cancer (CRC) disparities in the Midwest. The purpose of this study was to extrapolate results from in-depth interviews and brief surveys on the effectiveness of the church as a social marketer of CRC-prevention messages. Results show that pastors believe the congregation has limited knowledge about CRC risk and prevention; they also believe the church can improve cancer-prevention communication among members and those affiliated with the church.

  14. The use of Chinese herbal medicine as an adjuvant therapy to reduce incidence of chronic hepatitis in colon cancer patients: A Taiwanese population-based cohort study.

    Science.gov (United States)

    Lin, Tsai-Hui; Yen, Hung-Rong; Chiang, Jen-Huai; Sun, Mao-Feng; Chang, Hen-Hong; Huang, Sheng-Teng

    2017-04-18

    There is a decided lack of in-depth studies to evaluate the effectiveness of Chinese Herbal Medicine (CHM) as an adjuvant therapy on the incidence of chronic hepatitis in patients with colon cancer. The aim of this study is to assess whether CHM treatment decreased the incidence of chronic hepatitis in colon cancer patients who received conventional Western medical treatment. A Taiwanese nationwide population-based study of colon cancer patients receiving Western medicine treatment in conjunction with CHM treatment, using data provided by the National Health Insurance (NHI) Research Database, was conducted. A total of 61676 patients were diagnosed with colon cancer in Taiwan within the defined study period, from 1997 to 2010. After randomly equal matching for age, sex, excluding patients younger than 18 years of age, chronic hepatitis before colon cancer diagnosis date, receiving acupuncture and/or moxibustion and taking CHM for less than 30 days, data from 155 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence of CHM and the therapeutic potential of herbal products in treating patients with colon cancer. CHM used for patients with colon cancer exhibited significantly decreased incidence rates of chronic hepatitis [hazard ratio (HR)=0.53; 95% confidence interval (CI):0.38-0.74], with multivariate adjustment, compared to those without CHM use. The protective effect of CHM treatment with statistical significance across the stratification of age, gender, co-morbidity and treatment modality was noted. The cumulative incidence of chronic hepatitis was also reduced in patients with colon cancer receiving CHM treatment during a five-year period. In this study, we provide the ten most used single herbs and herbal formulas that were prescribed for patients with colon cancer; moreover, we identify the eight single herbs and five formulas used in CHM treatment which significantly decreased incidence of chronic

  15. Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic.

    Science.gov (United States)

    Meyskens, Frank L; Curt, Gregory A; Brenner, Dean E; Gordon, Gary; Herberman, Ronald B; Finn, Olivera; Kelloff, Gary J; Khleif, Samir N; Sigman, Caroline C; Szabo, Eva

    2011-03-01

    This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high(er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs.

  16. Transcriptomics and the Mediterranean Diet: A Systematic Review

    Science.gov (United States)

    Herrera-Marcos, Luis V.; Lou-Bonafonte, José M.; Arnal, Carmen; Navarro, María A.; Osada, Jesús

    2017-01-01

    The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases and cancer and in decreasing overall mortality. Nowadays, transcriptomics is gaining particular relevance due to the existence of non-coding RNAs capable of regulating many biological processes. The present work describes a systematic review of current evidence supporting the influence of the Mediterranean diet on transcriptomes of different tissues in various experimental models. While information on regulatory RNA is very limited, they seem to contribute to the effect. Special attention has been given to the oily matrix of virgin olive oil. In this regard, monounsaturated fatty acid-rich diets prevented the expression of inflammatory genes in different tissues, an action also observed after the administration of olive oil phenolic compounds. Among these, tyrosol, hydroxytyrosol, and secoiridoids have been found to be particularly effective in cell cycle expression. Less explored terpenes, such as oleanolic acid, are important modulators of circadian clock genes. The wide range of studied tissues and organisms indicate that response to these compounds is universal and poses an important level of complexity considering the different genes expressed in each tissue and the number of different tissues in an organism. PMID:28486416

  17. The role of hERG1 ion channels in epithelial-mesenchymal transition and the capacity of riluzole to reduce cisplatin resistance in colorectal cancer cells.