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Sample records for cancer reduces transcriptome

  1. A transcriptome anatomy of human colorectal cancers

    International Nuclear Information System (INIS)

    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. INsPeCT: INtegrative Platform for Cancer Transcriptomics

    OpenAIRE

    Madhamshettiwar, Piyush B; Maetschke, Stefan R; Davis, Melissa J; Antonio Reverter; Ragan, Mark A

    2014-01-01

    The emergence of transcriptomics, fuelled by high-throughput sequencing technologies, has changed the nature of cancer research and resulted in a massive accumulation of data. Computational analysis, integration, and data visualization are now major bottlenecks in cancer biology and translational research. Although many tools have been brought to bear on these problems, their use remains unnecessarily restricted to computational biologists, as many tools require scripting skills, data infrast...

  3. Transcriptome complexity in a genome-reduced bacterium

    DEFF Research Database (Denmark)

    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...

  4. Effects of smoking on oral cancer transcriptome

    OpenAIRE

    Zain, R. B.; Karen-Ng, L. P.; Cheong, S C; Anwar, A.; Mustaffa, W. M. W.; Prepagaran, N.; Zaini, Z.; Merican, A. F.; Abraham, M. T.; Tay, K. K.; Rahman, Z. A. A.; Jallaludin, A.

    2011-01-01

    Introduction: Oral cancer is a debilitating disease and the survival rates for these patients have not improved over the past decades. Tobacco smoking is one of the most common risk factor associated with oral cancer. Objectives: To explore and identify differential genes expression associated with tobacco smoking. Methodology: Next generation sequencing using the Illumina Genome Analyzer was done to sequence five fresh frozen oral cancer tissue samples from smoking patients, two of which wer...

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Transcriptome complexity in a genome-reduced bacterium.

    Science.gov (United States)

    Güell, Marc; van Noort, Vera; Yus, Eva; Chen, Wei-Hua; Leigh-Bell, Justine; Michalodimitrakis, Konstantinos; Yamada, Takuji; Arumugam, Manimozhiyan; Doerks, Tobias; Kühner, Sebastian; Rode, Michaela; Suyama, Mikita; Schmidt, Sabine; Gavin, Anne-Claude; Bork, Peer; Serrano, Luis

    2009-11-27

    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 previously undescribed, mostly noncoding transcripts, 89 of them in antisense configuration to known genes. We identified 341 operons, of which 139 are polycistronic; almost half of the latter show decaying expression in a staircase-like manner. Under various conditions, operons could be divided into 447 smaller transcriptional units, resulting in many alternative transcripts. Frequent antisense transcripts, alternative transcripts, and multiple regulators per gene imply a highly dynamic transcriptome, more similar to that of eukaryotes than previously thought.

  7. Transcriptome-wide targets of alternative splicing by RBM4 and possible role in cancer.

    Science.gov (United States)

    Markus, M Andrea; Yang, Yee Hwa J; Morris, Brian J

    2016-04-01

    This study determined transcriptome-wide targets of the splicing factor RBM4 using Affymetrix GeneChip(®) Human Exon 1.0 ST Arrays and HeLa cells treated with RBM4-specific siRNA. This revealed 238 transcripts that were targeted for alternative splicing. Cross-linking and immunoprecipitation experiments identified 945 RBM4 targets in mouse HEK293 cells, 39% of which were ascribed to "alternative splicing" by in silico pathway analysis. Mouse embryonic stem cells transfected with Rbm4 siRNA hairpins exhibited reduced colony numbers and size consistent with involvement of RBM4 in cell proliferation. RBM4 cDNA probing of a cancer cDNA array involving 18 different tumor types from 13 different tissues and matching normal tissue found overexpression of RBM4 mRNA (p<0.01) in cervical, breast, lung, colon, ovarian and rectal cancers. Many RBM4 targets we identified have been implicated in these cancers. In conclusion, our findings reveal transcriptome-wide targets of RBM4 and point to potential cancer-related targets and mechanisms that may involve RBM4. PMID:26898347

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

    Science.gov (United States)

    Culhane, A C; Howlin, J

    2007-12-01

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

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

    Directory of Open Access Journals (Sweden)

    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. Deep Sequencing the MicroRNA Transcriptome in Colorectal Cancer.

    Directory of Open Access Journals (Sweden)

    Kristina Schee

    Full Text Available Colorectal cancer (CRC is one of the leading causes of cancer related deaths and the search for prognostic biomarkers that might improve treatment decisions is warranted. MicroRNAs (miRNAs are short non-coding RNA molecules involved in regulating gene expression and have been proposed as possible biomarkers in CRC. In order to characterize the miRNA transcriptome, a large cohort including 88 CRC tumors with long-term follow-up was deep sequenced. 523 mature miRNAs were expressed in our cohort, and they exhibited largely uniform expression patterns across tumor samples. Few associations were found between clinical parameters and miRNA expression, among them, low expression of miR-592 and high expression of miR-10b-5p and miR-615-3p were associated with tumors located in the right colon relative to the left colon and rectum. High expression of miR-615-3p was also associated with poorly differentiated tumors. No prognostic biomarker candidates for overall and metastasis-free survival were identified by applying the LASSO method in a Cox proportional hazards model or univariate Cox. Examination of the five most abundantly expressed miRNAs in the cohort (miR-10a-5p, miR-21-5p, miR-22-3p, miR-143-3p and miR-192-5p revealed that their collective expression represented 54% of the detected miRNA sequences. Pathway analysis of the target genes regulated by the five most highly expressed miRNAs uncovered a significant number of genes involved in the CRC pathway, including APC, TGFβ and PI3K, thus suggesting that these miRNAs are relevant in CRC.

  11. Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration

    NARCIS (Netherlands)

    M. Smid (Marcel); F.G. Rodriguez-Gonzalez (F. German); A.M. Sieuwerts (Anieta); R. Salgado (Roberto); W.J.C. Prager-van der Smissen (Wendy); Vlugt-Daane, M.V.D. (Michelle Van Der); A. van Galen (Anne); S. Nik-Zainal (Serena); J. Staaf (Johan); A.B. Brinkman (Arie B.); M.J. Vijver (Marc ); A.L. Richardson (Andrea); A. Fatima (Aquila); Berentsen, K. (Kim); A. Butler (Adam); S. Martin (Sandra); H. Davies (Helen); J.E.M.A. Debets (Reno); M.E.M.-V. Gelder (Marion E. Meijer-Van); C.H.M. van Deurzen (Carolien); Macgrogan, G. (Gaëtan); Van Den Eynden, G.G.G.M. (Gert G. G. M.); C.A. Purdie (Colin A.); A.M. Thompson (Alastair M.); C. Caldas (Carlos); P.N. Span (Paul); Simpson, P.T. (Peter T.); S. Lakhani (Sunil); S.J. van Laere (Steven); C. Desmedt (Christine); Ringnér, M. (Markus); Tommasi, S. (Stefania); Eyford, J. (Jorunn); A. Broeks (Annegien); A. Vincent-Salomon (Anne); Futreal, P.A. (P. Andrew); S. Knappskog (Stian); King, T. (Tari); G. Thomas (Gilles); Viari, A. (Alain); Langerød, A. (Anita); A.-L. Borresen-Dale (Anne-Lise); E. Birney (Ewan); H. Stunnenberg (Henk); M.R. Stratton (Michael); J.A. Foekens (John); J.W.M. Martens (John)

    2016-01-01

    textabstractA recent comprehensive whole genome analysis of a large breast cancer cohort was used to link known and novel drivers and substitution signatures to the transcriptome of 266 cases. Here, we validate that subtype-specific aberrations show concordant expression changes for, for example, TP

  12. Transcriptome profiling of infectious diseases and cancer in zebrafish

    NARCIS (Netherlands)

    Ordas, Anita Katalin

    2010-01-01

    Analysis of the transcriptome, the total of all expressed RNA transcripts in a cell or an organism, contributes to our understanding of gene regulation during development and disease processes and is therefore of great importance in the field of genomic research. This thesis focuses on the analysis

  13. Reducing Your Risk of Cancer

    Science.gov (United States)

    ... Double contrast barium enema test Computed tomography Fecal DNA test Women aged 50 years and older Women aged ... the colon. Fecal Occult Blood Test (FOBT): A test of a stool sample for blood, which could be a sign of cancer ... “blueprints” that code for specific traits, such as ...

  14. The low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer.

    Science.gov (United States)

    Bizama, Carolina; Benavente, Felipe; Salvatierra, Edgardo; Gutiérrez-Moraga, Ana; Espinoza, Jaime A; Fernández, Elmer A; Roa, Iván; Mazzolini, Guillermo; Sagredo, Eduardo A; Gidekel, Manuel; Podhajcer, Osvaldo L

    2014-02-15

    Studies on the low-abundance transcriptome are of paramount importance for identifying the intimate mechanisms of tumor progression that can lead to novel therapies. The aim of the present study was to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analyses of the low-abundance transcriptome. The procedure involved an initial subtractive hybridization step, followed by global gene expression analysis using microarrays. We observed profound differences, both at the single gene and gene ontology levels, between the low-abundance transcriptome and the whole transcriptome. Analysis of the low-abundance transcriptome led to the identification and validation by tissue microarrays of novel biomarkers, such as LAMA3 and TTN; moreover, we identified cancer type-specific intracellular pathways and targetable genes, such as IRS2, IL17, IFNγ, VEGF-C, WISP1, FZD5 and CTBP1 that were not detectable by whole transcriptome analyses. We also demonstrated that knocking down the expression of CTBP1 sensitized gastric cancer cells to mainstay chemotherapeutic drugs. We conclude that the analysis of the low-abundance transcriptome provides useful insights into the molecular basis and treatment of cancer. PMID:23907728

  15. Low expression of leptin and its association with breast cancer: A transcriptomic study.

    Science.gov (United States)

    Karim, Sajjad; Merdad, Adnan; Schulten, Hans-Juergen; Jayapal, Manikandan; Dallol, Ashraf; Buhmeida, Abdelbaset; Al-Thubaity, Fatima; Mirza, Zeenat; Gari, Mamdooh A; Chaudhary, Adeel G; Abuzenadah, Adel M; Al-Qahtani, Mohammed H

    2016-07-01

    The incidence of breast cancer is alarmingly increasing worldwide and also among Saudi women. Obesity is linked with an increased cancer risk and studies have also revealed that leptin may be involved in breast tumorigenesis particularly among obese women. Numerous transcriptomic studies have been carried out worldwide; however, molecular studies among breast cancer patients of diverse ethnic groups from the Arabian Peninsula are scarce. In the present study, whole transcriptome analysis of 45 surgically resected breast tumors from Saudi Arabian female patients was carried out. Expression data were analyzed, and molecular networks and canonical pathways were identified. We identified 1,159 differentially expressed genes using p-value with a false discovery rate 2 as a cut-off. Using ingenuity pathway analysis tool, we identified many canonical pathways that were implicated in breast cancer for the first time. Notably, along with other lipid metabolism molecules, leptin (LEP)was one of the most downregulated genes (fold cut-off, -7.03) with significant differences between the breast cancer and the control groups (pcancer from a Saudi female population revealed downregulation of LEP. Molecular pathway analysis demonstrated the role of LEP and other associated molecules of the lipid metabolism pathway. Involvement of leptin and lipid metabolism in breast cancer was highlighted. The majority of cases presented were of late stage, stressing the need to educate individuals concerning early diagnostic testing and the life-style risk factors for breast cancer such as unhealthy diet and obesity. PMID:27177292

  16. Does Metformin Reduce Cancer Risks? Methodologic Considerations.

    Science.gov (United States)

    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.

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

    OpenAIRE

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

    2012-01-01

    In this work, the effect of rosemary extracts rich on polyphenols obtained using pressurized fluids was investigated on the gene expression of human SW480 and HT29 colon cancer cells. The application of transcriptomic profiling and functional enrichment analysis was done via two computational approaches, Ingenuity Pathway Analysis and Gene Set Enrichment Analysis. These two approaches were used for functional enrichment analysis as a previous step for a reliable interpretation of the data obt...

  18. Cancer core modules identification through genomic and transcriptomic changes correlation detection at network level

    Directory of Open Access Journals (Sweden)

    Li Wenting

    2012-06-01

    Full Text Available Abstract Background Identification of driver mutations among numerous genomic alternations remains a critical challenge to the elucidation of the underlying mechanisms of cancer. Because driver mutations by definition are associated with a greater number of cancer phenotypes compared to other mutations, we hypothesized that driver mutations could more easily be identified once the genotype-phenotype correlations are detected across tumor samples. Results In this study, we describe a novel network analysis to identify the driver mutation through integrating both cancer genomes and transcriptomes. Our method successfully identified a significant genotype-phenotype change correlation in all six solid tumor types and revealed core modules that contain both significantly enriched somatic mutations and aberrant expression changes specific to tumor development. Moreover, we found that the majority of these core modules contained well known cancer driver mutations, and that their mutated genes tended to occur at hub genes with central regulatory roles. In these mutated genes, the majority were cancer-type specific and exhibited a closer relationship within the same cancer type rather than across cancer types. The remaining mutated genes that exist in multiple cancer types led to two cancer type clusters, one cluster consisted of three neural derived or related cancer types, and the other cluster consisted of two adenoma cancer types. Conclusions Our approach can successfully identify the candidate drivers from the core modules. Comprehensive network analysis on the core modules potentially provides critical insights into convergent cancer development in different organs.

  19. Whole Grain Intake Reduces Pancreatic Cancer Risk

    OpenAIRE

    Lei, Qiucheng; Zheng, Huazhen; Bi, Jingcheng; Wang, Xinying; Jiang, Tingting; Gao, Xuejin; Tian, Feng; Xu, Min; Wu, Chao; Zhang, Li; Ning LI; Li, Jieshou

    2016-01-01

    Abstract Mounting evidence from epidemiology studies suggests that whole grain intake may reduce pancreatic cancer risk, but convincing evidence is scarce. We conducted a meta-analysis to assess the association between whole grain intake and pancreatic cancer risk. Relevant observational studies were identified by searching PubMed, Embase, Scopus, and Cochrane library databases for the period from January 1980 to July 2015, with no restrictions. We calculated the summary odds ratios (ORs) for...

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Elucidation of how cancer cells avoid acidosis through comparative transcriptomic data analysis.

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    Kun Xu

    Full Text Available The rapid growth of cancer cells fueled by glycolysis produces large amounts of protons in cancer cells, which tri mechanisms to transport them out, hence leading to increased acidity in their extracellular environments. It has been well established that the increased acidity will induce cell death of normal cells but not cancer cells. The main question we address here is: how cancer cells deal with the increased acidity to avoid the activation of apoptosis. We have carried out a comparative analysis of transcriptomic data of six solid cancer types, breast, colon, liver, two lung (adenocarcinoma, squamous cell carcinoma and prostate cancers, and proposed a model of how cancer cells utilize a few mechanisms to keep the protons outside of the cells. The model consists of a number of previously, well or partially, studied mechanisms for transporting out the excess protons, such as through the monocarboxylate transporters, V-ATPases, NHEs and the one facilitated by carbonic anhydrases. In addition we propose a new mechanism that neutralizes protons through the conversion of glutamate to γ-aminobutyrate, which consumes one proton per reaction. We hypothesize that these processes are regulated by cancer related conditions such as hypoxia and growth factors and by the pH levels, making these encoded processes not available to normal cells under acidic conditions.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Transfer RNA-derived small RNAs in the cancer transcriptome

    OpenAIRE

    Green, Darrell; Fraser, William; Dalmay, Tamas

    2016-01-01

    The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such...

  4. A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer

    Science.gov (United States)

    Auslander, Noam; Yizhak, Keren; Weinstock, Adam; Budhu, Anuradha; Tang, Wei; Wang, Xin Wei; Ambs, Stefan; Ruppin, Eytan

    2016-07-01

    Disrupted regulation of cellular processes is considered one of the hallmarks of cancer. We analyze metabolomic and transcriptomic profiles jointly collected from breast cancer and hepatocellular carcinoma patients to explore the associations between the expression of metabolic enzymes and the levels of the metabolites participating in the reactions they catalyze. Surprisingly, both breast cancer and hepatocellular tumors exhibit an increase in their gene-metabolites associations compared to noncancerous adjacent tissues. Following, we build predictors of metabolite levels from the expression of the enzyme genes catalyzing them. Applying these predictors to a large cohort of breast cancer samples we find that depleted levels of key cancer-related metabolites including glucose, glycine, serine and acetate are significantly associated with improved patient survival. Thus, we show that the levels of a wide range of metabolites in breast cancer can be successfully predicted from the transcriptome, going beyond the limited set of those measured.

  5. Integrated genome and transcriptome sequencing identifies a novel form of hybrid and aggressive prostate cancer.

    Science.gov (United States)

    Wu, Chunxiao; Wyatt, Alexander W; Lapuk, Anna V; McPherson, Andrew; McConeghy, Brian J; Bell, Robert H; Anderson, Shawn; Haegert, Anne; Brahmbhatt, Sonal; Shukin, Robert; Mo, Fan; Li, Estelle; Fazli, Ladan; Hurtado-Coll, Antonio; Jones, Edward C; Butterfield, Yaron S; Hach, Faraz; Hormozdiari, Fereydoun; Hajirasouliha, Iman; Boutros, Paul C; Bristow, Robert G; Jones, Steven Jm; Hirst, Martin; Marra, Marco A; Maher, Christopher A; Chinnaiyan, Arul M; Sahinalp, S Cenk; Gleave, Martin E; Volik, Stanislav V; Collins, Colin C

    2012-05-01

    Next-generation sequencing is making sequence-based molecular pathology and personalized oncology viable. We selected an individual initially diagnosed with conventional but aggressive prostate adenocarcinoma and sequenced the genome and transcriptome from primary and metastatic tissues collected prior to hormone therapy. The histology-pathology and copy number profiles were remarkably homogeneous, yet it was possible to propose the quadrant of the prostate tumour that likely seeded the metastatic diaspora. Despite a homogeneous cell type, our transcriptome analysis revealed signatures of both luminal and neuroendocrine cell types. Remarkably, the repertoire of expressed but apparently private gene fusions, including C15orf21:MYC, recapitulated this biology. We hypothesize that the amplification and over-expression of the stem cell gene MSI2 may have contributed to the stable hybrid cellular identity. This hybrid luminal-neuroendocrine tumour appears to represent a novel and highly aggressive case of prostate cancer with unique biological features and, conceivably, a propensity for rapid progression to castrate-resistance. Overall, this work highlights the importance of integrated analyses of genome, exome and transcriptome sequences for basic tumour biology, sequence-based molecular pathology and personalized oncology.

  6. Multi-study integration of brain cancer transcriptomes reveals organ-level molecular signatures.

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    Jaeyun Sung

    Full Text Available We utilized abundant transcriptomic data for the primary classes of brain cancers to study the feasibility of separating all of these diseases simultaneously based on molecular data alone. These signatures were based on a new method reported herein--Identification of Structured Signatures and Classifiers (ISSAC--that resulted in a brain cancer marker panel of 44 unique genes. Many of these genes have established relevance to the brain cancers examined herein, with others having known roles in cancer biology. Analyses on large-scale data from multiple sources must deal with significant challenges associated with heterogeneity between different published studies, for it was observed that the variation among individual studies often had a larger effect on the transcriptome than did phenotype differences, as is typical. For this reason, we restricted ourselves to studying only cases where we had at least two independent studies performed for each phenotype, and also reprocessed all the raw data from the studies using a unified pre-processing pipeline. We found that learning signatures across multiple datasets greatly enhanced reproducibility and accuracy in predictive performance on truly independent validation sets, even when keeping the size of the training set the same. This was most likely due to the meta-signature encompassing more of the heterogeneity across different sources and conditions, while amplifying signal from the repeated global characteristics of the phenotype. When molecular signatures of brain cancers were constructed from all currently available microarray data, 90% phenotype prediction accuracy, or the accuracy of identifying a particular brain cancer from the background of all phenotypes, was found. Looking forward, we discuss our approach in the context of the eventual development of organ-specific molecular signatures from peripheral fluids such as the blood.

  7. 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

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

    International Nuclear Information System (INIS)

    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

  9. Low dose irradiation reduces cancer mortality rates

    Energy Technology Data Exchange (ETDEWEB)

    Luckey, T.D.

    2000-05-01

    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 hlumg 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 {sup 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

  10. 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.

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

    Science.gov (United States)

    ... Cancers Breast Cancer Screening Research Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival For some ... after Beginning 5 or 10 Years of Adjuvant Tamoxifen 5 Years 10 Years Risk of Recurrence 25. ...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-04-01

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

  13. Whole Grain Intake Reduces Pancreatic Cancer Risk

    Science.gov (United States)

    Lei, Qiucheng; Zheng, Huazhen; Bi, Jingcheng; Wang, Xinying; Jiang, Tingting; Gao, Xuejin; Tian, Feng; Xu, Min; Wu, Chao; Zhang, Li; Li, Ning; Li, Jieshou

    2016-01-01

    Abstract Mounting evidence from epidemiology studies suggests that whole grain intake may reduce pancreatic cancer risk, but convincing evidence is scarce. We conducted a meta-analysis to assess the association between whole grain intake and pancreatic cancer risk. Relevant observational studies were identified by searching PubMed, Embase, Scopus, and Cochrane library databases for the period from January 1980 to July 2015, with no restrictions. We calculated the summary odds ratios (ORs) for pancreatic cancer using random-effects model meta-analysis. Between-study heterogeneity was analyzed using the I2 statistic. A total of 8 studies regarding whole grain intake were included in the meta-analysis. The pooled OR of pancreatic cancer for those with high versus low whole grain intake was 0.76 (95% confidence interval [CI], 0.64–0.91; P = 0.002). There was no significant heterogeneity across these studies (I2 = 11.7%; Pheterogeneity = 0.339). In the subgroup analysis by geographic area, the summary ORs of developing pancreatic cancer were 0.64 (95% CI, 0.53–0.79; P < 0.001; I2 = 0%; Pheterogeneity = 0.482) in the United States (n = 4) and 0.95 (95% CI, 0.63–1.43; P = 0.803; I2 = 45.6%; Pheterogeneity = 0.175) in Europe (n = 2). In the subgroup analysis by type of whole grain, the summary ORs were 0.72 (95% CI, 0.60–0.87; P = .001; I2 = 0; Pheterogeneity = 0.876) for grains (n = 4) and 0.74 (95% CI, 0.27–2.02; P = 0.554; I2 = 86.3%; Pheterogeneity = 0.007) for wheat (n = 2). A high intake of whole grains was associated with a reduced risk of pancreatic cancer. Because of the absent of more cohort studies, further prospective studies need to be conducted to ensure conclusions that are more robust. PMID:26945361

  14. 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

  15. Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers

    Science.gov (United States)

    Shen, Yao; Kim, Arianna L.; Du, Rong; Liu, Liang

    2016-01-01

    Exposure to ultraviolet radiation (UVR) is a major risk factor for both melanoma and non-melanoma skin cancers. In addition to its mutagenic effect, UVR can also induce substantial transcriptional instability in skin cells affecting thousands of genes, including many cancer genes, suggesting that transcriptional instability may be another important etiological factor in skin photocarcinogenesis. In this study, we performed detailed transcriptomic profiling studies to characterize the kinetic changes in global gene expression in human keratinocytes exposed to different UVR conditions. We identified a subset of UV-responsive genes as UV signature genes (UVSGs) based on 1) conserved UV-responsiveness of this subset of genes among different keratinocyte lines; and 2) UV-induced persistent changes in their mRNA levels long after exposure. Interestingly, 11 of the UVSGs were shown to be critical to skin cancer cell proliferation and survival. Through computational Gene Set Enrichment Analysis, we demonstrated that a significant portion of the UVSGs were dysregulated in human skin squamous cell carcinomas, but not in other human malignancies. This highlights the potential and specificity of the UVSGs in clinical diagnosis of UV damage and stratification of skin cancer risk. PMID:27643989

  16. Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers.

    Science.gov (United States)

    Shen, Yao; Kim, Arianna L; Du, Rong; Liu, Liang

    2016-01-01

    Exposure to ultraviolet radiation (UVR) is a major risk factor for both melanoma and non-melanoma skin cancers. In addition to its mutagenic effect, UVR can also induce substantial transcriptional instability in skin cells affecting thousands of genes, including many cancer genes, suggesting that transcriptional instability may be another important etiological factor in skin photocarcinogenesis. In this study, we performed detailed transcriptomic profiling studies to characterize the kinetic changes in global gene expression in human keratinocytes exposed to different UVR conditions. We identified a subset of UV-responsive genes as UV signature genes (UVSGs) based on 1) conserved UV-responsiveness of this subset of genes among different keratinocyte lines; and 2) UV-induced persistent changes in their mRNA levels long after exposure. Interestingly, 11 of the UVSGs were shown to be critical to skin cancer cell proliferation and survival. Through computational Gene Set Enrichment Analysis, we demonstrated that a significant portion of the UVSGs were dysregulated in human skin squamous cell carcinomas, but not in other human malignancies. This highlights the potential and specificity of the UVSGs in clinical diagnosis of UV damage and stratification of skin cancer risk. PMID:27643989

  17. Extensive Transcriptomic and Genomic Analysis Provides New Insights about Luminal Breast Cancers

    Science.gov (United States)

    Tishchenko, Inna; Milioli, Heloisa Helena; Riveros, Carlos; Moscato, Pablo

    2016-01-01

    Despite constituting approximately two thirds of all breast cancers, the luminal A and B tumours are poorly classified at both clinical and molecular levels. There are contradictory reports on the nature of these subtypes: some define them as intrinsic entities, others as a continuum. With the aim of addressing these uncertainties and identifying molecular signatures of patients at risk, we conducted a comprehensive transcriptomic and genomic analysis of 2,425 luminal breast cancer samples. Our results indicate that the separation between the molecular luminal A and B subtypes—per definition—is not associated with intrinsic characteristics evident in the differentiation between other subtypes. Moreover, t-SNE and MST-kNN clustering approaches based on 10,000 probes, associated with luminal tumour initiation and/or development, revealed the close connections between luminal A and B tumours, with no evidence of a clear boundary between them. Thus, we considered all luminal tumours as a single heterogeneous group for analysis purposes. We first stratified luminal tumours into two distinct groups by their HER2 gene cluster co-expression: HER2-amplified luminal and ordinary-luminal. The former group is associated with distinct transcriptomic and genomic profiles, and poor prognosis; it comprises approximately 8% of all luminal cases. For the remaining ordinary-luminal tumours we further identified the molecular signature correlated with disease outcomes, exhibiting an approximately continuous gene expression range from low to high risk. Thus, we employed four virtual quantiles to segregate the groups of patients. The clinico-pathological characteristics and ratios of genomic aberrations are concordant with the variations in gene expression profiles, hinting at a progressive staging. The comparison with the current separation into luminal A and B subtypes revealed a substantially improved survival stratification. Concluding, we suggest a review of the definition of

  18. Proteomic and meta-transcriptomic study on lymph node metastasis in gastric cancer

    Directory of Open Access Journals (Sweden)

    Hiroshi Ichikawa

    2014-06-01

    Full Text Available To examine the proteomic background of lymph node metastasis (LNM in gastric cancer, we performed protein expression profiling of paired non-tumor, primary tumor, and LNM tissues. Using a label-free proteomic approach, we generated protein expression profiles of 3894 unique proteins and identified 109 differentially expressed proteins. Functional pathway analysis of the differentially expressed proteins showed that members of the beta-3 integrin (ITGB3 pathway were significantly enriched. Aberrations of ITGB3 were reported in various malignancies; however, ITGB3 in LNM tissues has not been examined to date. Different level of ITGB3 expression was confirmed in 20 gastric cancer cases by Western blotting. We analyzed the mRNA levels of the differentially expressed proteins by using a public mRNA expression database; 38.8% of the proteins examined, including those involved in oxidation and reduction, showed correlation between protein and mRNA levels. Proteins without such correlation included factors related to cell adhesion. Our study suggests a novel role for the integrin pathway in the development of LNM in gastric cancer and indicated possible benefits of observational transcriptomic analysis for proteomic studies.

  19. Long-range Transcriptome Sequencing Reveals Cancer Cell Growth Regulatory Chimeric mRNA

    Directory of Open Access Journals (Sweden)

    Roberto Plebani

    2012-11-01

    Full Text Available mRNA chimeras from chromosomal translocations often play a role as transforming oncogenes. However, cancer transcriptomes also contain mRNA chimeras that may play a role in tumor development, which arise as transcriptional or post-transcriptional events. To identify such chimeras, we developed a deterministic screening strategy for long-range sequence analysis. High-throughput, long-read sequencing was then performed on cDNA libraries from major tumor histotypes and corresponding normal tissues. These analyses led to the identification of 378 chimeras, with an unexpectedly high frequency of expression (≈2 x 10-5 of all mRNA. Functional assays in breast and ovarian cancer cell lines showed that a large fraction of mRNA chimeras regulates cell replication. Strikingly, chimeras were shown to include both positive and negative regulators of cell growth, which functioned as such in a cell-type-specific manner. Replication-controlling chimeras were found to be expressed by most cancers from breast, ovary, colon, uterus, kidney, lung, and stomach, suggesting a widespread role in tumor development.

  20. 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

    RNAs which are upregulated in cancer, defining promoters which overlap with repetitive elements (especially SINE/Alu and LTR/ERV1 elements) that are often upregulated in cancer. Lastly, we documented for the first time upregulation of multiple copies of the REP522 interspersed repeat in cancer. Overall...

  1. 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)

    Prostate cancer cells in primary tumors have been typed CD10-/CD13-/CD24hi/CD26+/CD38lo/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

  2. ExSurv: A Web Resource for Prognostic Analyses of Exons Across Human Cancers Using Clinical Transcriptomes.

    Science.gov (United States)

    Hashemikhabir, Seyedsasan; Budak, Gungor; Janga, Sarath Chandra

    2016-01-01

    Survival analysis in biomedical sciences is generally performed by correlating the levels of cellular components with patients' clinical features as a common practice in prognostic biomarker discovery. While the common and primary focus of such analysis in cancer genomics so far has been to identify the potential prognostic genes, alternative splicing - a posttranscriptional regulatory mechanism that affects the functional form of a protein due to inclusion or exclusion of individual exons giving rise to alternative protein products, has increasingly gained attention due to the prevalence of splicing aberrations in cancer transcriptomes. Hence, uncovering the potential prognostic exons can not only help in rationally designing exon-specific therapeutics but also increase specificity toward more personalized treatment options. To address this gap and to provide a platform for rational identification of prognostic exons from cancer transcriptomes, we developed ExSurv (https://exsurv.soic.iupui.edu), a web-based platform for predicting the survival contribution of all annotated exons in the human genome using RNA sequencing-based expression profiles for cancer samples from four cancer types available from The Cancer Genome Atlas. ExSurv enables users to search for a gene of interest and shows survival probabilities for all the exons associated with a gene and found to be significant at the chosen threshold. ExSurv also includes raw expression values across the cancer cohort as well as the survival plots for prognostic exons. Our analysis of the resulting prognostic exons across four cancer types revealed that most of the survival-associated exons are unique to a cancer type with few processes such as cell adhesion, carboxylic, fatty acid metabolism, and regulation of T-cell signaling common across cancer types, possibly suggesting significant differences in the posttranscriptional regulatory pathways contributing to prognosis. PMID:27528797

  3. ExSurv: A Web Resource for Prognostic Analyses of Exons Across Human Cancers Using Clinical Transcriptomes

    Science.gov (United States)

    Hashemikhabir, Seyedsasan; Budak, Gungor; Janga, Sarath Chandra

    2016-01-01

    Survival analysis in biomedical sciences is generally performed by correlating the levels of cellular components with patients’ clinical features as a common practice in prognostic biomarker discovery. While the common and primary focus of such analysis in cancer genomics so far has been to identify the potential prognostic genes, alternative splicing – a posttranscriptional regulatory mechanism that affects the functional form of a protein due to inclusion or exclusion of individual exons giving rise to alternative protein products, has increasingly gained attention due to the prevalence of splicing aberrations in cancer transcriptomes. Hence, uncovering the potential prognostic exons can not only help in rationally designing exon-specific therapeutics but also increase specificity toward more personalized treatment options. To address this gap and to provide a platform for rational identification of prognostic exons from cancer transcriptomes, we developed ExSurv (https://exsurv.soic.iupui.edu), a web-based platform for predicting the survival contribution of all annotated exons in the human genome using RNA sequencing-based expression profiles for cancer samples from four cancer types available from The Cancer Genome Atlas. ExSurv enables users to search for a gene of interest and shows survival probabilities for all the exons associated with a gene and found to be significant at the chosen threshold. ExSurv also includes raw expression values across the cancer cohort as well as the survival plots for prognostic exons. Our analysis of the resulting prognostic exons across four cancer types revealed that most of the survival-associated exons are unique to a cancer type with few processes such as cell adhesion, carboxylic, fatty acid metabolism, and regulation of T-cell signaling common across cancer types, possibly suggesting significant differences in the posttranscriptional regulatory pathways contributing to prognosis. PMID:27528797

  4. A comparison of single molecule and amplification based sequencing of cancer transcriptomes.

    Directory of Open Access Journals (Sweden)

    Lee T Sam

    Full Text Available The second wave of next generation sequencing technologies, referred to as single-molecule sequencing (SMS, carries the promise of profiling samples directly without employing polymerase chain reaction steps used by amplification-based sequencing (AS methods. To examine the merits of both technologies, we examine mRNA sequencing results from single-molecule and amplification-based sequencing in a set of human cancer cell lines and tissues. We observe a characteristic coverage bias towards high abundance transcripts in amplification-based sequencing. A larger fraction of AS reads cover highly expressed genes, such as those associated with translational processes and housekeeping genes, resulting in relatively lower coverage of genes at low and mid-level abundance. In contrast, the coverage of high abundance transcripts plateaus off using SMS. Consequently, SMS is able to sequence lower- abundance transcripts more thoroughly, including some that are undetected by AS methods; however, these include many more mapping artifacts. A better understanding of the technical and analytical factors introducing platform specific biases in high throughput transcriptome sequencing applications will be critical in cross platform meta-analytic studies.

  5. Genome and transcriptome delineation of two major oncogenic pathways governing invasive ductal breast cancer development

    Science.gov (United States)

    Aswad, Luay; Yenamandra, Surya Pavan; Ow, Ghim Siong; Grinchuk, Oleg; Ivshina, Anna V.; Kuznetsov, Vladimir A.

    2015-01-01

    Invasive ductal carcinoma (IDC) is a major histo-morphologic type of breast cancer. Histological grading (HG) of IDC is widely adopted by oncologists as a prognostic factor. However, HG evaluation is highly subjective with only 50%–85% inter-observer agreements. Specifically, the subjectivity in the assignment of the intermediate grade (histologic grade 2, HG2) breast cancers (comprising ~50% of IDC cases) results in uncertain disease outcome prediction and sub-optimal systemic therapy. Despite several attempts to identify the mechanisms underlying the HG classification, their molecular bases are poorly understood. We performed integrative bioinformatics analysis of TCGA and several other cohorts (total 1246 patients). We identified a 22-gene tumor aggressiveness grading classifier (22g-TAG) that reflects global bifurcation in the IDC transcriptomes and reclassified patients with HG2 tumors into two genetically and clinically distinct subclasses: histological grade 1-like (HG1-like) and histological grade 3-like (HG3-like). The expression profiles and clinical outcomes of these subclasses were similar to the HG1 and HG3 tumors, respectively. We further reclassified IDC into low genetic grade (LGG = HG1+HG1-like) and high genetic grade (HGG = HG3-like+HG3) subclasses. For the HG1-like and HG3-like IDCs we found subclass-specific DNA alterations, somatic mutations, oncogenic pathways, cell cycle/mitosis and stem cell-like expression signatures that discriminate between these tumors. We found similar molecular patterns in the LGG and HGG tumor classes respectively. Our results suggest the existence of two genetically-predefined IDC classes, LGG and HGG, driven by distinct oncogenic pathways. They provide novel prognostic and therapeutic biomarkers and could open unique opportunities for personalized systemic therapies of IDC patients. PMID:26474389

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

    International Nuclear Information System (INIS)

    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

  7. The Colorectal cancer disease-specific transcriptome may facilitate the discovery of more biologically and clinically relevant information

    Directory of Open Access Journals (Sweden)

    Proutski Vitali

    2010-12-01

    Full Text Available Abstract Background To date, there are no clinically reliable predictive markers of response to the current treatment regimens for advanced colorectal cancer. The aim of the current study was to compare and assess the power of transcriptional profiling using a generic microarray and a disease-specific transcriptome-based microarray. We also examined the biological and clinical relevance of the disease-specific transcriptome. Methods DNA microarray profiling was carried out on isogenic sensitive and 5-FU-resistant HCT116 colorectal cancer cell lines using the Affymetrix HG-U133 Plus2.0 array and the Almac Diagnostics Colorectal cancer disease specific Research tool. In addition, DNA microarray profiling was also carried out on pre-treatment metastatic colorectal cancer biopsies using the colorectal cancer disease specific Research tool. The two microarray platforms were compared based on detection of probesets and biological information. Results The results demonstrated that the disease-specific transcriptome-based microarray was able to out-perform the generic genomic-based microarray on a number of levels including detection of transcripts and pathway analysis. In addition, the disease-specific microarray contains a high percentage of antisense transcripts and further analysis demonstrated that a number of these exist in sense:antisense pairs. Comparison between cell line models and metastatic CRC patient biopsies further demonstrated that a number of the identified sense:antisense pairs were also detected in CRC patient biopsies, suggesting potential clinical relevance. Conclusions Analysis from our in vitro and clinical experiments has demonstrated that many transcripts exist in sense:antisense pairs including IGF2BP2, which may have a direct regulatory function in the context of colorectal cancer. While the functional relevance of the antisense transcripts has been established by many studies, their functional role is currently unclear

  8. European Code against Cancer 4th Edition: 12 ways to reduce your cancer risk.

    Science.gov (United States)

    Schüz, Joachim; Espina, Carolina; Villain, Patricia; Herrero, Rolando; Leon, Maria E; Minozzi, Silvia; Romieu, Isabelle; Segnan, Nereo; Wardle, Jane; Wiseman, Martin; Belardelli, Filippo; Bettcher, Douglas; Cavalli, Franco; Galea, Gauden; Lenoir, Gilbert; Martin-Moreno, Jose M; Nicula, Florian Alexandru; Olsen, Jørgen H; Patnick, Julietta; Primic-Zakelj, Maja; Puska, Pekka; van Leeuwen, Flora E; Wiestler, Otmar; Zatonski, Witold

    2015-12-01

    This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer. PMID:26164654

  9. 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.

  10. Eat well, keep well and reduce your risk of cancer

    OpenAIRE

    Public Health Agency

    2010-01-01

    This leaflet highlights Northern Ireland's incidence of cancer as an important public health concern, and explains how eating more fruit, vegetables and other fibre rich foods can significantly reduce our risk of getting the disease.

  11. Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis

    Directory of Open Access Journals (Sweden)

    Gabet Yankel

    2010-09-01

    Full Text Available Abstract Background Prostate cancer (PCa cells preferentially metastasize to bone at least in part by acquiring osteomimetic properties. Runx2, an osteoblast master transcription factor, is aberrantly expressed in PCa cells, and promotes their metastatic phenotype. The transcriptional programs regulated by Runx2 have been extensively studied during osteoblastogenesis, where it activates or represses target genes in a context-dependent manner. However, little is known about the gene regulatory networks influenced by Runx2 in PCa cells. We therefore investigated genome wide mRNA expression changes in PCa cells in response to Runx2. Results We engineered a C4-2B PCa sub-line called C4-2B/Rx2dox, in which Doxycycline (Dox treatment stimulates Runx2 expression from very low to levels observed in other PCa cells. Transcriptome profiling using whole genome expression array followed by in silico analysis indicated that Runx2 upregulated a multitude of genes with prominent cancer associated functions. They included secreted factors (CSF2, SDF-1, proteolytic enzymes (MMP9, CST7, cytoskeleton modulators (SDC2, Twinfilin, SH3PXD2A, intracellular signaling molecules (DUSP1, SPHK1, RASD1 and transcription factors (Sox9, SNAI2, SMAD3 functioning in epithelium to mesenchyme transition (EMT, tissue invasion, as well as homing and attachment to bone. Consistent with the gene expression data, induction of Runx2 in C4-2B cells enhanced their invasiveness. It also promoted cellular quiescence by blocking the G1/S phase transition during cell cycle progression. Furthermore, the cell cycle block was reversed as Runx2 levels declined after Dox withdrawal. Conclusions The effects of Runx2 in C4-2B/Rx2dox cells, as well as similar observations made by employing LNCaP, 22RV1 and PC3 cells, highlight multiple mechanisms by which Runx2 promotes the metastatic phenotype of PCa cells, including tissue invasion, homing to bone and induction of high bone turnover. Runx2 is

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

    International Nuclear Information System (INIS)

    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

  13. 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...

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

    Science.gov (United States)

    Lanou, Amy Joy; Svenson, Barbara

    2010-01-01

    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. PMID:21407994

  15. 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

  16. A high-resolution transcriptome map of cell cycle reveals novel connections between periodic genes and cancer.

    Science.gov (United States)

    Dominguez, Daniel; Tsai, Yi-Hsuan; Gomez, Nicholas; Jha, Deepak Kumar; Davis, Ian; Wang, Zefeng

    2016-08-01

    Progression through the cell cycle is largely dependent on waves of periodic gene expression, and the regulatory networks for these transcriptome dynamics have emerged as critical points of vulnerability in various aspects of tumor biology. Through RNA-sequencing of human cells during two continuous cell cycles (>2.3 billion paired reads), we identified over 1 000 mRNAs, non-coding RNAs and pseudogenes with periodic expression. Periodic transcripts are enriched in functions related to DNA metabolism, mitosis, and DNA damage response, indicating these genes likely represent putative cell cycle regulators. Using our set of periodic genes, we developed a new approach termed "mitotic trait" that can classify primary tumors and normal tissues by their transcriptome similarity to different cell cycle stages. By analyzing >4 000 tumor samples in The Cancer Genome Atlas (TCGA) and other expression data sets, we found that mitotic trait significantly correlates with genetic alterations, tumor subtype and, notably, patient survival. We further defined a core set of 67 genes with robust periodic expression in multiple cell types. Proteins encoded by these genes function as major hubs of protein-protein interaction and are mostly required for cell cycle progression. The core genes also have unique chromatin features including increased levels of CTCF/RAD21 binding and H3K36me3. Loss of these features in uterine and kidney cancers is associated with altered expression of the core 67 genes. Our study suggests new chromatin-associated mechanisms for periodic gene regulation and offers a predictor of cancer patient outcomes. PMID:27364684

  17. Transcriptome Analysis of Piperlongumine-Treated Human Pancreatic Cancer Cells Reveals Involvement of Oxidative Stress and Endoplasmic Reticulum Stress Pathways.

    Science.gov (United States)

    Dhillon, Harsharan; Mamidi, Sujan; McClean, Phillip; Reindl, Katie M

    2016-06-01

    Piperlongumine (PL), an alkaloid obtained from long peppers, displays antitumorigenic properties for a variety of human cell- and animal-based models. The aim of this study was to identify the underlying molecular mechanisms for PL anticancer effects on human pancreatic cancer cells. RNA sequencing (RNA-seq) was used to identify the effects of PL on the transcriptome of MIA PaCa-2 human pancreatic cancer cells. PL treatment of pancreatic cancer cells resulted in differential expression of 683 mRNA transcripts with known protein functions, 351 of which were upregulated and 332 of which were downregulated compared to control-treated cells. Transcripts associated with oxidative stress, endoplasmic reticulum (ER) stress, and unfolded protein response pathways were significantly overexpressed with PL treatment. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to validate the RNA-seq results, which included upregulation of HO-1, IRE1α, cytochrome c, and ASNS. The results provide key insight into the mechanisms by which PL alters cancer cell physiology and identify that activation of oxidative stress and ER stress pathways is a critical avenue for PL anticancer effects. PMID:27119744

  18. 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.

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

    Science.gov (United States)

    Braakhuis, Andrea J; Campion, Peta; Bishop, Karen S

    2016-01-01

    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. PMID:27608040

  20. 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.

  1. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer.

    Science.gov (United States)

    Bowtell, David D; Böhm, Steffen; Ahmed, Ahmed A; Aspuria, Paul-Joseph; Bast, Robert C; Beral, Valerie; Berek, Jonathan S; Birrer, Michael J; Blagden, Sarah; Bookman, Michael A; Brenton, James D; Chiappinelli, Katherine B; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G; Iwanicki, Marcin; Karlan, Beth Y; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A; Lu, Karen H; McNeish, Iain A; Menon, Usha; Narod, Steven A; Nelson, Brad H; Nephew, Kenneth P; Pharoah, Paul; Powell, Daniel J; Ramos, Pilar; Romero, Iris L; Scott, Clare L; Sood, Anil K; Stronach, Euan A; Balkwill, Frances R

    2015-11-01

    High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. PMID:26493647

  2. How surgical innovation reduced death and suffering from prostate cancer.

    Science.gov (United States)

    Walsh, Patrick C

    2013-01-01

    Radical prostatectomy for the cure of prostate cancer never gained widespread popularity because of severe side effects: all men were impotent, many were totally incontinent, and when performed by the retropubic approach, bleeding was often life threatening. When I arrived at Johns Hopkins in 1974 as the new director of the Brady Urological Institute, I embarked upon a series of anatomic studies to determine the source of this morbidity. Using the operating room as an anatomy laboratory and performing dissections in stillborn male infants, it was possible to define important, previously unrecognized anatomic structures. Application of these discoveries to the surgical technique made it possible to preserve sexual function, reduce urinary continence to a minimum, and perform the procedure in a relative bloodless field. Armed with the ability to cure prostate cancer more safely with surgery and with fewer side effects, radical prostatectomy was rapidly adopted and in the following decade death from prostate cancer declined by 40%.

  3. 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

  4. Large-scale transcriptome analyses reveal new genetic marker candidates of head, neck, and thyroid cancer

    DEFF Research Database (Denmark)

    Reis, Eduardo M; Ojopi, Elida P B; Alberto, Fernando L;

    2005-01-01

    curation, pointing to 788 putatively new alternative splicing isoforms, the majority (75%) being insertion events. A subset of 34 new splicing isoforms (5% of 788 events) was selected and 23 (68%) were confirmed by reverse transcription-PCR and DNA sequencing. Putative new genes were revealed, including...... with detailed clinical data about tumor origin, the information reported here is now publicly available on a dedicated Web site as a resource for further biological investigation. This first in silico reconstruction of the head, neck, and thyroid transcriptomes points to a wealth of new candidate markers...

  5. Reduced serum selenoprotein P concentrations in German prostate cancer patients.

    Science.gov (United States)

    Meyer, Hellmuth-Alexander; Hollenbach, Birgit; Stephan, Carsten; Endermann, Tobias; Morgenthaler, Nils G; Cammann, Henning; Köhrle, Josef; Jung, Klaus; Schomburg, Lutz

    2009-09-01

    Selenium (Se) is essentially needed for the biosynthesis of selenoproteins. Low Se intake causes reduced selenoprotein biosynthesis and constitutes a risk factor for tumorigenesis. Accordingly, some Se supplementation trials have proven effective to reduce prostate cancer risk, especially in poorly supplied individuals. Because Se metabolism is controlled by selenoprotein P (SEPP), we have tested whether circulating SEPP concentrations correlate to prostate cancer stage and grade. A total of 190 men with prostate cancer (n = 90) and "no evidence of malignancy" (NEM; n = 100) histologically confirmed by prostate biopsy were retrospectively analyzed for established tumor markers and for their Se and SEPP status. Prostate specific antigen (PSA), free PSA, total Se, and SEPP concentrations were determined from serum samples and compared with clinicopathologic parameters. The diagnostic performance was analyzed with receiver operating characteristic curves. Median Se and SEPP concentrations differed significantly (P curve (AUC) of a marker combination with age, PSA, and percent free PSA (%fPSA) in combination with the SEPP concentration, yielded the highest diagnostic value (AUC 0.80) compared with the marker combination without SEPP (AUC 0.77) or %fPSA (AUC 0.76). We conclude that decreased SEPP concentration in serum might represent an additional valuable marker for prostate cancer diagnostics. PMID:19690186

  6. Evaluating shielding effectiveness for reducing space radiation cancer risks

    International Nuclear Information System (INIS)

    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

  7. Evaluating Shielding Effectiveness for Reducing Space Radiation Cancer Risks

    Science.gov (United States)

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

    2007-01-01

    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 PDF s are used in significance tests of 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 PDF s. Competing mortality risks and functional correlations in radiation quality factor uncertainties are treated in the calculations. We show that the cancer risk uncertainty, defined as the ratio of the 95% confidence level (CL) to the point estimate is about 4-fold for lunar and Mars mission risk projections. For short-stay lunar missions (risk, however one that is mitigated effectively by shielding, especially for carbon composites structures with high hydrogen content. In contrast, for long duration lunar (>180 d) or Mars missions, GCR risks may exceed radiation risk limits, with 95% CL s 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 can not be shown to significantly reduce risk compared to aluminum shielding based on a significance test that accounts for radiobiology uncertainties in GCR risk projection.

  8. Reducing bone cancer cell functions using selenium nanocomposites.

    Science.gov (United States)

    Stolzoff, Michelle; Webster, Thomas J

    2016-02-01

    Cancer recurrence at the site of tumor resection remains a major threat to patient survival despite modern cancer therapeutic advances. Osteosarcoma, in particular, is a very aggressive primary bone cancer that commonly recurs after surgical resection, radiation, and chemotherapeutic treatment. The objective of the present in vitro study was to develop a material that could decrease bone cancer cell recurrence while promoting healthy bone cell functions. Selenium is a natural part of our diet which has shown promise for reducing cancer cell functions, inhibiting bacteria, and promoting healthy cells functions, yet, it has not been widely explored for osteosarcoma applications. For this purpose, due to their increased surface area, selenium nanoparticles (SeNP) were precipitated on a very common orthopedic tissue engineering material, poly-l-lactic acid (or PLLA). Selenium-coated PLLA materials were shown to selectively decrease long-term osteosarcoma cell density while promoting healthy, noncancerous, osteoblast functions (for example, up to two times more alkaline phosphatase activity on selenium coated compared to osteoblasts grown on typical tissue culture plates), suggesting they should be further studied for replacing tumorous bone tissue with healthy bone tissue. Importantly, results of this study were achieved without the use of chemotherapeutics or pharmaceutical agents, which have negative side effects. PMID:26454004

  9. Ginger Helps Reduce Nausea from Chemotherapy | Division of Cancer Prevention

    Science.gov (United States)

    Ginger helped prevent or reduce chemotherapy-induced nausea when taken with traditional anti-nausea drugs by patients with cancer, researchers have found. The results are from a randomized, double-blind, placebo-controlled clinical trial, the largest study to examine the potential effects of ginger on chemotherapy-related nausea. The study will be presented May 30 at the ASCO annual meeting in Orlando, FL. |

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

    International Nuclear Information System (INIS)

    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)

  11. 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.

  12. Elevation of sulfatides in ovarian cancer: An integrated transcriptomic and lipidomic analysis including tissue-imaging mass spectrometry

    Directory of Open Access Journals (Sweden)

    McDonald John F

    2010-07-01

    explanation for the higher ST. Conclusions This study combined transcriptomic and lipidomic approaches to establish that sulfatides are elevated in ovarian cancer and should be evaluated further as factors that might be important in ovarian cancer biology and, possibly, as biomarkers.

  13. 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.

  14. Reducing inequities in colorectal cancer screening in North America

    Directory of Open Access Journals (Sweden)

    Kathleen M Decker

    2014-01-01

    Full Text Available Colorectal cancer (CRC is an important cause of mortality and morbidity in North America. Screening using a fecal occult blood test, flexible sigmoidoscopy, or colonoscopy reduces CRC mortality through the detection and treatment of precancerous polyps and early stage CRC. Although CRC screening participation has increased in recent years, large inequities still exist. Minorities, new immigrants, and those with lower levels of education or income are much less likely to be screened. This review provides an overview of the commonly used tests for CRC screening, disparities in CRC screening, and promising methods at the individual, provider, and system levels to reduce these disparities. Overall, to achieve high CRC participation rates and reduce the burden of CRC in the population, a multi-faceted approach that uses strategies at all levels to reduce CRC screening disparities is urgently required.

  15. Genomic instability influences the transcriptome and proteome in endometrial cancer subtypes

    OpenAIRE

    Habermann Jens K; Bündgen Nana K; Gemoll Timo; Hautaniemi Sampsa; Lundgren Caroline; Wangsa Danny; Doering Jana; Bruch Hans-Peter; Nordstroem Britta; Roblick Uwe J; Jörnvall Hans; Auer Gert; Ried Thomas

    2011-01-01

    Abstract Background In addition to clinical characteristics, DNA aneuploidy has been identified as a prognostic factor in epithelial malignancies in general and in endometrial cancers in particular. We mapped ploidy-associated chromosomal aberrations and identified corresponding gene and protein expression changes in endometrial cancers of different prognostic subgroups. Methods DNA image cytometry classified 25 endometrioid cancers to be either diploid (n = 16) or aneuploid (n = 9), and all ...

  16. Transcriptomic signature of Bexarotene (Rexinoid LGD1069 on mammary gland from three transgenic mouse mammary cancer models

    Directory of Open Access Journals (Sweden)

    Bissonnette Reid P

    2008-09-01

    Full Text Available Abstract Background The rexinoid bexarotene (LGD1069, Targretin is a highly selective retinoid × receptor (RXR agonist that inhibits the growth of pre-malignant and malignant breast cells. Bexarotene was shown to suppress the development of breast cancer in transgenic mice models without side effects. The chemopreventive effects of bexarotene are due to transcriptional modulation of cell proliferation, differentiation and apoptosis. Our goal in the present study was to obtain a profile of the genes modulated by bexarotene on mammary gland from three transgenic mouse mammary cancer models in an effort to elucidate its molecular mechanism of action and for the identification of biomarkers of effectiveness. Methods Serial analysis of gene expression (SAGE was employed to profile the transcriptome of p53-null, MMTV-ErbB2, and C3(1-SV40 mammary cells obtained from mice treated with bexarotene and their corresponding controls. Results This resulted in a dataset of approximately 360,000 transcript tags representing over 20,000 mRNAs from a total of 6 different SAGE libraries. Analysis of gene expression changes induced by bexarotene in mammary gland revealed that 89 genes were dysregulated among the three transgenic mouse mammary models. From these, 9 genes were common to the three models studied. Conclusion Analysis of the indicated core of transcripts and protein-protein interactions of this commonly modulated genes indicate two functional modules significantly affected by rexinoid bexarotene related to protein biosynthesis and bioenergetics signatures, in addition to the targeting of cancer-causing genes related with cell proliferation, differentiation and apoptosis.

  17. 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.

  18. 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...... 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...

  19. Genomic instability influences the transcriptome and proteome in endometrial cancer subtypes

    Directory of Open Access Journals (Sweden)

    Habermann Jens K

    2011-10-01

    Full Text Available Abstract Background In addition to clinical characteristics, DNA aneuploidy has been identified as a prognostic factor in epithelial malignancies in general and in endometrial cancers in particular. We mapped ploidy-associated chromosomal aberrations and identified corresponding gene and protein expression changes in endometrial cancers of different prognostic subgroups. Methods DNA image cytometry classified 25 endometrioid cancers to be either diploid (n = 16 or aneuploid (n = 9, and all uterine papillary serous cancers (UPSC to be aneuploid (n = 8. All samples were subjected to comparative genomic hybridization and gene expression profiling. Identified genes were subjected to Ingenuity pathway analysis (IPA and were correlated to protein expression changes. Results Comparative genomic hybridization revealed ploidy-associated specific, recurrent genomic imbalances. Gene expression analysis identified 54 genes between diploid and aneuploid endometrioid carcinomas, 39 genes between aneuploid endometrioid cancer and UPSC, and 76 genes between diploid endometrioid and aneuploid UPSC to be differentially expressed. Protein profiling identified AKR7A2 and ANXA2 to show translational alterations consistent with the transcriptional changes. The majority of differentially expressed genes and proteins belonged to identical molecular functions, foremost Cancer, Cell Death, and Cellular Assembly and Organization. Conclusions We conclude that the grade of genomic instability rather than the histopathological subtype correlates with specific gene and protein expression changes. The identified genes and proteins might be useful as molecular targets for improved diagnostic and therapeutic intervention and merit prospective validation.

  20. A whole-genome sequence and transcriptome perspective on HER2-positive breast cancers.

    Science.gov (United States)

    Ferrari, Anthony; Vincent-Salomon, Anne; Pivot, Xavier; Sertier, Anne-Sophie; Thomas, Emilie; Tonon, Laurie; Boyault, Sandrine; Mulugeta, Eskeatnaf; Treilleux, Isabelle; MacGrogan, Gaëtan; Arnould, Laurent; Kielbassa, Janice; Le Texier, Vincent; Blanché, Hélène; Deleuze, Jean-François; Jacquemier, Jocelyne; Mathieu, Marie-Christine; Penault-Llorca, Frédérique; Bibeau, Frédéric; Mariani, Odette; Mannina, Cécile; Pierga, Jean-Yves; Trédan, Olivier; Bachelot, Thomas; Bonnefoi, Hervé; Romieu, Gilles; Fumoleau, Pierre; Delaloge, Suzette; Rios, Maria; Ferrero, Jean-Marc; Tarpin, Carole; Bouteille, Catherine; Calvo, Fabien; Gut, Ivo Glynne; Gut, Marta; Martin, Sancha; Nik-Zainal, Serena; Stratton, Michael R; Pauporté, Iris; Saintigny, Pierre; Birnbaum, Daniel; Viari, Alain; Thomas, Gilles

    2016-01-01

    HER2-positive breast cancer has long proven to be a clinically distinct class of breast cancers for which several targeted therapies are now available. However, resistance to the treatment associated with specific gene expressions or mutations has been observed, revealing the underlying diversity of these cancers. Therefore, understanding the full extent of the HER2-positive disease heterogeneity still remains challenging. Here we carry out an in-depth genomic characterization of 64 HER2-positive breast tumour genomes that exhibit four subgroups, based on the expression data, with distinctive genomic features in terms of somatic mutations, copy-number changes or structural variations. The results suggest that, despite being clinically defined by a specific gene amplification, HER2-positive tumours melt into the whole luminal-basal breast cancer spectrum rather than standing apart. The results also lead to a refined ERBB2 amplicon of 106 kb and show that several cases of amplifications are compatible with a breakage-fusion-bridge mechanism. PMID:27406316

  1. Improving Pathological Assessment of Breast Cancer by Employing Array-Based Transcriptome Analysis

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Mihály

    2013-08-01

    Full Text Available Breast cancer research has paved the way of personalized oncology with the introduction of hormonal therapy and the measurement of estrogen receptor as the first widely accepted clinical biomarker. The expression of another receptor—HER2/ERBB2/neu—was initially a sign of worse prognosis, but targeted therapy has granted improved outcome for these patients so that today HER2 positive patients have better prognosis than HER2 negative patients. Later, the introduction of multigene assays provided the pathologists with an unbiased assessment of the tumors’ molecular fingerprint. The recent FDA approval of complete microarray pipelines has opened new possibilities for the objective classification of breast cancer samples. Here we review the applications of microarrays for determining ER and HER2 status, molecular subtypes as well as predicting prognosis and grade for breast cancer patients. An open question remains the role of single genes within such signatures. Openly available microarray datasets enable the execution of an independent cross-validation of new marker and signature candidates. In summary, we review the current state regarding clinical applications of microarrays in breast cancer molecular pathology.

  2. Transcriptomic and Protein Expression Analysis Reveals Clinicopathological Significance of Bloom Syndrome Helicase (BLM) in Breast Cancer.

    Science.gov (United States)

    Arora, Arvind; Abdel-Fatah, Tarek M A; Agarwal, Devika; Doherty, Rachel; Moseley, Paul M; Aleskandarany, Mohammed A; Green, Andrew R; Ball, Graham; Alshareeda, Alaa T; Rakha, Emad A; Chan, Stephen Y T; Ellis, Ian O; Madhusudan, Srinivasan

    2015-04-01

    Bloom syndrome helicase (BLM) has key roles in homologous recombination repair, telomere maintenance, and DNA replication. Germ-line mutations in the BLM gene causes Bloom syndrome, a rare disorder characterized by premature aging and predisposition to multiple cancers, including breast cancer. The clinicopathologic significance of BLM in sporadic breast cancers is unknown. We investigated BLM mRNA expression in the Molecular Taxonomy of Breast Cancer International Consortium cohort (n = 1,950) and validated in an external dataset of 2,413 tumors. BLM protein level was evaluated in the Nottingham Tenovus series comprising 1,650 breast tumors. BLM mRNA overexpression was significantly associated with high histologic grade, larger tumor size, estrogen receptor-negative (ER(-)), progesterone receptor-negative (PR(-)), and triple-negative phenotypes (ps < 0.0001). BLM mRNA overexpression was also linked to aggressive molecular phenotypes, including PAM50.Her2 (P < 0.0001), PAM50.Basal (P < 0.0001), and PAM50.LumB (P < 0.0001) and Genufu subtype (ER(+)/Her2(-)/high proliferation; P < 0.0001). PAM50.LumA tumors and Genufu subtype (ER(+)/Her2(-)/low proliferation) were more likely to express low levels of BLM mRNA (ps < 0.0001). Integrative molecular clusters (intClust) intClust.1 (P < 0.0001), intClust.5 (P < 0.0001), intClust.9 (P < 0.0001), and intClust.10 (P < 0.0001) were also more likely in tumors with high BLM mRNA expression. BLM mRNA overexpression was associated with poor breast cancer-specific survival (BCSS; ps < 0.000001). At the protein level, altered subcellular localization with high cytoplasmic BLM and low nuclear BLM was linked to aggressive phenotypes. In multivariate analysis, BLM mRNA and BLM protein levels independently influenced BCSS. This is the first and the largest study to provide evidence that BLM is a promising biomarker in breast cancer. PMID:25673821

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

    Science.gov (United States)

    Carrier, Marilyn; Joint, Mathilde; Lutzing, Régis; Page, Adeline; Rochette-Egly, Cécile

    2016-01-01

    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. PMID:27362937

  4. The American Cancer Society challenge goal to reduce US cancer mortality by 50% between 1990 and 2015: Results and reflections.

    Science.gov (United States)

    Byers, Tim; Wender, Richard C; Jemal, Ahmedin; Baskies, Arnold M; Ward, Elizabeth E; Brawley, Otis W

    2016-09-01

    In 1996, the Board of Directors of the American Cancer Society (ACS) challenged the United States to reduce what looked to be possible peak cancer mortality in 1990 by 50% by the year 2015. This analysis examines the trends in cancer mortality across this 25-year challenge period from 1990 to 2015. In 2015, cancer death rates were 26% lower than in 1990 (32% lower among men and 22% lower among women). The 50% reduction goal was more fully met for the cancer sites for which there was enactment of effective approaches for prevention, early detection, and/or treatment. Among men, mortality rates dropped for lung cancer by 45%, for colorectal cancer by 47%, and for prostate cancer by 53%. Among women, mortality rates dropped for lung cancer by 8%, for colorectal cancer by 44%, and for breast cancer by 39%. Declines in the death rates of all other cancer sites were substantially smaller (13% among men and 17% among women). The major factors that accounted for these favorable trends were progress in tobacco control and improvements in early detection and treatment. As we embark on new national cancer goals, this recent past experience should teach us that curing the cancer problem will require 2 sets of actions: making new discoveries in cancer therapeutics and more completely applying those discoveries in cancer prevention we have already made. CA Cancer J Clin 2016;66:359-369. © 2016 American Cancer Society.

  5. Modelling p-value distributions to improve theme-driven survival analysis of cancer transcriptome datasets

    Directory of Open Access Journals (Sweden)

    Brors Benedikt

    2010-01-01

    Full Text Available Abstract Background Theme-driven cancer survival studies address whether the expression signature of genes related to a biological process can predict patient survival time. Although this should ideally be achieved by testing two separate null hypotheses, current methods treat both hypotheses as one. The first test should assess whether a geneset, independent of its composition, is associated with prognosis (frequently done with a survival test. The second test then verifies whether the theme of the geneset is relevant (usually done with an empirical test that compares the geneset of interest with random genesets. Current methods do not test this second null hypothesis because it has been assumed that the distribution of p-values for random genesets (when tested against the first null hypothesis is uniform. Here we demonstrate that such an assumption is generally incorrect and consequently, such methods may erroneously associate the biology of a particular geneset with cancer prognosis. Results To assess the impact of non-uniform distributions for random genesets in such studies, an automated theme-driven method was developed. This method empirically approximates the p-value distribution of sets of unrelated genes based on a permutation approach, and tests whether predefined sets of biologically-related genes are associated with survival. The results from a comparison with a published theme-driven approach revealed non-uniform distributions, suggesting a significant problem exists with false positive rates in the original study. When applied to two public cancer datasets our technique revealed novel ontological categories with prognostic power, including significant correlations between "fatty acid metabolism" with overall survival in breast cancer, as well as "receptor mediated endocytosis", "brain development", "apical plasma membrane" and "MAPK signaling pathway" with overall survival in lung cancer. Conclusions Current methods of theme

  6. Surgery to Reduce the Risk of Breast Cancer

    Science.gov (United States)

    ... breast-cancer prevention in postmenopausal women. New England Journal of Medicine 2011; 364(25):2381–2391. [PubMed Abstract] Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI ...

  7. Reducing Barriers to Use of Breast Cancer Screening

    Science.gov (United States)

    Investigation to determine whether a telephone counseling intervention aimed at women who are known to underuse breast cancer screening can with, or without, an accompanying educational intervention for their physicians, increase use of breast cancer screening.

  8. 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.

  9. 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. PMID:26859767

  10. Citrus Fruit Intake Substantially Reduces the Risk of Esophageal Cancer

    OpenAIRE

    Wang, Anqiang; Zhu, Chengpei; Fu, Lilan; Wan, Xueshuai; Yang, Xiaobo; Zhang, Haohai; Miao, Ruoyu; He, Lian; Sang, Xinting; ZHAO, HAITAO

    2015-01-01

    Abstract Many epidemiologic studies indicate a potential association between fruit and vegetable intake and various cancers. The purpose of this meta-analysis is to investigate the association between citrus fruit intake and esophageal cancer risk. The authors conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Library from inception until July 2014. Studies presenting information about citrus intake and esophageal cancer were analyzed. The authors extracted the categories of...

  11. Relaxation Acupressure Reduces Persistent Cancer-Related Fatigue

    OpenAIRE

    Zick, Suzanna M; Sara Alrawi; Gary Merel; Brodie Burris; Ananda Sen; Amie Litzinger; Harris, Richard E.

    2010-01-01

    Persistent cancer-related fatigue (PCRF) is a symptom experienced by many cancer survivors. Acupressure offers a potential treatment for PCRF. We investigated if acupressure treatments with opposing actions would result in differential effects on fatigue and examined the effect of different “doses” of acupressure on fatigue. We performed a trial of acupressure in cancer survivors experiencing moderate to severe PCRF. Participants were randomized to one of three treatment groups: relaxation ac...

  12. How to reduce your cancer risk: mechanisms and myths

    OpenAIRE

    Nahleh Z; Bhatti NS; Mal M

    2011-01-01

    Zeina Nahleh1, Narinder Singh Bhatti2, Meenakshi Mal21Division of Hematology-Oncology, Department of Internal Medicine, TTUHSC-Paul L Foster School of Medicine, El Paso, TX, USA; 2Dayanand Medical College and Hospital, Ludhiana, Punjab, IndiaAbstract: Cancer prevention continues to be a high research priority and the most optimal way to ultimately lower the economic and psychological burden of cancer. Many known risk factors associated with cancer are related to dietary and lifestyle factors ...

  13. Identification of RECQ1-regulated transcriptome uncovers a role of RECQ1 in regulation of cancer cell migration and invasion

    Science.gov (United States)

    Li, Xiao Ling; Lu, Xing; Parvathaneni, Swetha; Bilke, Sven; Zhang, Hongen; Thangavel, Saravanabhavan; Vindigni, Alessandro; Hara, Toshifumi; Zhu, Yuelin; Meltzer, Paul S; Lal, Ashish; Sharma, Sudha

    2014-01-01

    The RECQ protein family of helicases has critical roles in protecting and stabilizing the genome. Three of the 5 known members of the human RecQ family are genetically linked with cancer susceptibility syndromes, but the association of the most abundant human RecQ homolog, RECQ1, with cellular transformation is yet unclear. RECQ1 is overexpressed in a variety of human cancers, indicating oncogenic functions. Here, we assessed genome-wide changes in gene expression upon knockdown of RECQ1 in HeLa and MDA-MB-231 cells. Pathway analysis suggested that RECQ1 enhances the expression of multiple genes that play key roles in cell migration, invasion, and metastasis, including EZR, ITGA2, ITGA3, ITGB4, SMAD3, and TGFBR2. Consistent with these results, silencing RECQ1 significantly reduced cell migration and invasion. In comparison to genome-wide annotated promoter regions, the promoters of genes downregulated upon RECQ1 silencing were significantly enriched for a potential G4 DNA forming sequence motif. Chromatin immunoprecipitation assays demonstrated binding of RECQ1 to the G4 motifs in the promoters of select genes downregulated upon RECQ1 silencing. In breast cancer patients, the expression of a subset of RECQ1-activated genes positively correlated with RECQ1 expression. Moreover, high RECQ1 expression was associated with poor prognosis in breast cancer. Collectively, our findings identify a novel function of RECQ1 in gene regulation and indicate that RECQ1 contributes to tumor development and progression, in part, by regulating the expression of key genes that promote cancer cell migration, invasion and metastasis. PMID:25483193

  14. 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. PMID:26910411

  15. Reducing inequalities in lung cancer incidence through smoking policies

    NARCIS (Netherlands)

    I. Soerjomataram; J.J. Barendregt; C. Gartner; A. Kunst; H. Moller; M. Avendano

    2011-01-01

    Introduction: Lower social class has higher lung cancer incidence, largely attributable to higher smoking prevalence among the lower social classes. We assessed the magnitude and time dimension of potential impact of targeted interventions on smoking on socioeconomic inequalities in lung cancer. Met

  16. Religion and reduced cancer risk: what is the explanation?

    DEFF Research Database (Denmark)

    Hoff, Andreas; Johannessen-Henry, Christine Tind; Ross, Lone;

    2008-01-01

    40 years. In the studies in which adjustment was made only for age and sex, reductions were observed in the risks for lifestyle-associated cancers, i.e. those associated with tobacco smoking, alcohol consumption, diet, physical activity and reproductive factors. In the studies in which adjustment......Several studies of members of Christian religious communities have shown significantly lower risks for certain cancers amongst members than in the general population. We identified 17 epidemiological studies of the risk for cancer amongst members of Christian communities published during the past...... 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...

  17. Neoadjuvant chemotherapy for locally advanced cervical cancer reduces surgical risks and lymph-vascular space involvement

    OpenAIRE

    Wang, Yue; Wang, Guang; Wei, Li-Hui; Huang, Ling-Hui; Wang, Jian-Liu; Wang, Shi-Jun; Li, Xiao-Ping; Shen, Dan-Hua; Bao, Dong-Mei; Gao, Jian

    2011-01-01

    Neoadjuvant chemotherapy (NACT), which can reduce the size and therefore increase the resectability of tumors, has recently evolved as a treatment for locally advanced cervical cancer. NACT has been reported to decrease the risk of pathologic factors related to prognosis of cervical cancer. To further assess the effects of NACT on surgery and the pathologic characteristics of cervical cancer, we reviewed 110 cases of locally advanced cervical cancer treated with radical hysterectomy with or w...

  18. Linalool is a PPARα ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome.

    Science.gov (United States)

    Jun, Hee-Jin; Lee, Ji Hae; Kim, Jiyoung; Jia, Yaoyao; Kim, Kyoung Heon; Hwang, Kwang Yeon; Yun, Eun Ju; Do, Kyoung-Rok; Lee, Sung-Joon

    2014-06-01

    We investigated the hypotriglyceridemic mechanism of action of linalool, an aromatic monoterpene present in teas and fragrant herbs. Reporter gene and time-resolved fluorescence resonance energy transfer assays demonstrated that linalool is a direct ligand of PPARα. Linalool stimulation reduced cellular lipid accumulation regulating PPARα-responsive genes and significantly induced FA oxidation, and its effects were markedly attenuated by silencing PPARα expression. In mice, the oral administration of linalool for 3 weeks reduced plasma TG concentrations in Western-diet-fed C57BL/6J mice (31%, P linalool stimulation rewired global gene expression in lipid-loaded hepatocytes and that the effects of 1 mM linalool were comparable to those of 0.1 mM fenofibrate. Metabolomic analysis of the mouse plasma revealed that the global metabolite profiles were significantly distinguishable between linalool-fed mice and controls. Notably, the concentrations of saturated FAs were significantly reduced in linalool-fed mice. These findings suggest that the appropriate intake of a natural aromatic compound could exert beneficial metabolic effects by regulating a cellular nutrient sensor.

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

    Science.gov (United States)

    Taking adjuvant tamoxifen for 10 years after primary treatment leads to a greater reduction in breast cancer recurrences and deaths than taking the drug for only 5 years, according to the results of a large international clinical trial.

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

    OpenAIRE

    Amy Joy Lanou; Barbara Svenson

    2010-01-01

    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 veg...

  1. Identification of key components in the energy metabolism of the hyperthermophilic sulfate reducing archaeon Archaeoglobus fulgidus by transcriptome analyses

    Directory of Open Access Journals (Sweden)

    William Peter eHocking

    2014-03-01

    Full Text Available Energy conservation by the pathway of dissimilatory sulfate reduction is present in a diverse group of prokaryotes, but is most comprehensively studied in Deltaproteobacteria. Herein, whole-genome microarray analyses where used to provide a model of the energy me-tabolism of the sulfate reducing archaeon Archaeoglobus fulgidus, based comparative analysis litoautotrophic growth with H2/CO2 and thiosulfate, and heterotrophic growth on lactate with sulfate or thiosulfate. Only 72 genes were expressed differentially between the cultures utiliz-ing sulfate or thiosulfate whereas 269 genes were affected by a shift in energy source. We identified co-located gene cluster encoding putative lactate dehydrogenases (lldD, dld, lldEFG, also present in sulfate reducing bacteria. These enzymes may take part in energy conservation in A. fulgidus by specifically linking lactate oxidation with APS reduction via the Qmo complex. High transcriptional levels of Fqo confirm an important role of F420H2 and menaquinone mediated electron transport chain during heterotrophic growth. A putative pe-riplasmic thiosulfate reductase was identified by specific up-regulation. Also, putative genes for transport of sulfate and sulfite are discussed. We present a model for hydrogen metabo-lism, based on the probable bifurcation reaction of the Mvh:Hdl hydrogenase, that may inhibit the utilization of Fdred for energy conservation. Rather, energy conservation is probably facili-tated via menaquinone to multiple membrane bound heterodisulfide reductase complexes and the enzyme DsrC – linking periplasmic hydrogenase (Vht to the cytoplasmic reduction of sulfite. The ambiguous roles of genes corresponding to fatty acid metabolism induced during growth with H2 are discussed. Putative co-assimilation of organic acids is favored over a homologues secondary carbon fixation pathway, although both mechanisms may contribute to conserve the amount of Fdred needed during autotrophic growth

  2. Colchicine Significantly Reduces Incident Cancer in Gout Male Patients

    Science.gov (United States)

    Kuo, Ming-Chun; Chang, Shun-Jen; Hsieh, Ming-Chia

    2015-01-01

    Abstract Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77–0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout. PMID:26683907

  3. 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. PMID:26975043

  4. Exemestane Following Tamoxifen Reduces Breast Cancer Recurrences and Prolongs Survival

    Science.gov (United States)

    Postmenopausal women with early-stage hormone receptor-positive breast cancer had delayed disease recurrence and longer survival after taking 2-3 years of tamoxifen followed by exemestane for a total of 5 years compared to taking tamoxifen for 5 years.

  5. Reducing aluminum: an occupation possibly associated with bladder cancer.

    Science.gov (United States)

    Thériault, G; De Guire, L; Cordier, S

    1981-02-15

    A case-control study, undertaken to identify reasons for the exceptionally high incidence of bladder cancer among men in the Chicoutimi census division of the province of Quebec, revealed an increased risk associated with employment in the electrolysis department of an aluminum reduction plant. The estimated relative risk was 2.83 (95% confidence interval; 1.06 to 7.54). An interaction was found between such employment and cigarette smoking, resulting in a combined relative risk of 5.70 (95% confidence interval: 2.00 to 12.30). These findings suggest that employment in an aluminum reduction plant accounts for part of the excess of bladder cancer in the region studied.

  6. NGS meta data analysis for identification of SNP and INDEL patterns in human airway transcriptome: A preliminary indicator for lung cancer

    Directory of Open Access Journals (Sweden)

    Sathya B.

    2015-03-01

    Full Text Available High-throughput sequencing of RNA (RNA-Seq was developed primarily to analyze global gene expression in different tissues. It is also an efficient way to discover coding SNPs and when multiple individuals with different genetic backgrounds were used, RNA-Seq is very effective for the identification of SNPs. The objective of this study was to perform SNP and INDEL discoveries in human airway transcriptome of healthy never smokers, healthy current smokers, smokers without lung cancer and smokers with lung cancer. By preliminary comparative analysis of these four data sets, it is expected to get SNP and INDEL patterns responsible for lung cancer. A total of 85,028 SNPs and 5738 INDELs in healthy never smokers, 32,671 SNPs and 1561 INDELs in healthy current smokers, 50,205 SNPs and 3008 INDELs in smokers without lung cancer and 51,299 SNPs and 3138 INDELs in smokers with lung cancer were identified. The analysis of the SNPs and INDELs in genes that were reported earlier as differentially expressed was also performed. It has been found that a smoking person has SNPs at position 62,186,542 and 62,190,293 in SCGB1A1 gene and 180,017,251, 180,017,252, and 180,017,597 in SCGB3A1 gene and INDELs at position 35,871,168 in NFKBIA gene and 180,017,797 in SCGB3A1 gene. The SNPs identified in this study provides a resource for genetic studies in smokers and shall contribute to the development of a personalized medicine. This study is only a preliminary kind and more vigorous data analysis and wet lab validation are required.

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

    DEFF Research Database (Denmark)

    Borges, Álvaro H; 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...

  8. NIH study finds regular aspirin use may reduce ovarian cancer risk

    Science.gov (United States)

    Women who take aspirin daily may reduce their risk of ovarian cancer by 20 percent, according to a study by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health. However, further research is needed before clinical r

  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. Exemestane Reduces Breast Cancer Risk in High-Risk Postmenopausal Women

    Science.gov (United States)

    Clinical trial results presented at the 2011 ASCO annual meeting showed that the aromatase inhibitor exemestane—used to treat early and advanced breast cancer—substantially reduced the risk of invasive breast cancer in high-risk postmenopausal women.

  11. 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.

  12. Investigation of radiation-induced transcriptome profile of radioresistant non-small cell lung cancer A549 cells using RNA-seq.

    Directory of Open Access Journals (Sweden)

    Hee Jung Yang

    Full Text Available Radioresistance is a main impediment to effective radiotherapy for non-small cell lung cancer (NSCLC. Despite several experimental and clinical studies of resistance to radiation, the precise mechanism of radioresistance in NSCLC cells and tissues still remains unclear. This result could be explained by limitation of previous researches such as a partial understanding of the cellular radioresistance mechanism at a single molecule level. In this study, we aimed to investigate extensive radiation responses in radioresistant NSCLC cells and to identify radioresistance-associating factors. For the first time, using RNA-seq, a massive sequencing-based approach, we examined whole-transcriptome alteration in radioresistant NSCLC A549 cells under irradiation, and verified significant radiation-altered genes and their chromosome distribution patterns. Also, bioinformatic approaches (GO analysis and IPA were performed to characterize the radiation responses in radioresistant A549 cells. We found that epithelial-mesenchymal transition (EMT, migration and inflammatory processes could be meaningfully related to regulation of radiation responses in radioresistant A549 cells. Based on the results of bioinformatic analysis for the radiation-induced transcriptome alteration, we selected seven significant radiation-altered genes (SESN2, FN1, TRAF4, CDKN1A, COX-2, DDB2 and FDXR and then compared radiation effects in two types of NSCLC cells with different radiosensitivity (radioresistant A549 cells and radiosensitive NCI-H460 cells. Interestingly, under irradiation, COX-2 showed the most significant difference in mRNA and protein expression between A549 and NCI-H460 cells. IR-induced increase of COX-2 expression was appeared only in radioresistant A549 cells. Collectively, we suggest that COX-2 (also known as prostaglandin-endoperoxide synthase 2 (PTGS2 could have possibility as a putative biomarker for radioresistance in NSCLC cells.

  13. 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.

  14. Genistein-Inhibited Cancer Stem Cell-Like Properties and Reduced Chemoresistance of Gastric Cancer

    OpenAIRE

    Weifeng Huang; Chunpeng Wan; Qicong Luo; Zhengjie Huang; Qi Luo

    2014-01-01

    Genistein, the predominant isoflavone found in soy products, has exerted its anticarcinogenic effect in many different tumor types in vitro and in vivo. Accumulating evidence in recent years has strongly indicated the existence of cancer stem cells in gastric cancer. Here, we showed that low doses of genistein (15 µM), extracted from Millettia nitida Benth var hirsutissima Z Wei, inhibit tumor cell self-renewal in two types of gastric cancer cells by colony formation assay and tumor sphere f...

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

    International Nuclear Information System (INIS)

    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

  16. 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.

  17. 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.

  18. 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.

    2011-01-01

    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 reduc

  19. Matrine reduces the proliferation and invasion of colorectal cancer cells via reducing the activity of p38 signaling pathway.

    Science.gov (United States)

    Ren, Hongtao; Zhang, Shuqun; Ma, Hongbing; Wang, Yali; Liu, Di; Wang, Xijing; Wang, Zhongwei

    2014-12-01

    Matrine has been used in anti-inflammatory and anti-cancer therapies for a long time. However, the anti-metastatic effect and related mechanism(s) in colorectal cancer (CRC) are still unclear. In this study, we investigated whether the administration of matrine could inhibit the proliferation, motility, and invasion of human CRC cells via regulating p38 signaling pathway. Results showed that matrine inhibited migration and invasion of CRC cells in vitro and in vivo. Additionally, after being treated with matrine for 24 h, the expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 as well as proteinase activity in CRC cells were reduced in a dose-dependent manner. Moreover, matrine reduced the phosphorylation level of p38 obviously. Combined treatment with p38 inhibitor (SB203580) and matrine resulted in a synergistic reduction of invasion as well as MMP-2/-9 expression in CRC cells. It was also found that matrine inhibited the proliferation and metastasis of CRC tumor in vivo. In conclusion, p38 signaling pathway may involve in matrine's inhibitory effects on migration and invasion of CRC cells by reducing the expression of MMP-2/-9, suggesting that matrine may be a potential therapeutic agent for CRC.

  20. 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

  1. Exon-level transcriptome profiling in murine breast cancer reveals splicing changes specific to tumors with different metastatic abilities.

    Directory of Open Access Journals (Sweden)

    Amandine Bemmo

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

  2. Enhancing Supportive-Educative Nursing Systems to Reduce Risk of Post-Breast Cancer Lymphedema

    OpenAIRE

    Jane M Armer; Shook, Robin P.; Schneider, Melanie K; Brooks, Constance W.; Peterson, Julie; Stewart, Bob R.

    2009-01-01

    This study describes the use of data regarding self-care agency to enhance a supportive-educative nursing system for breast cancer survivors to reduce the risk of developing lymphedema post surgery. Impetus for this study came from the analysis of participant feedback from a parent study (Lance Armstrong Foundation pilot study) that sought to plan an educational program for nurses that will improve their supportive-educative nursing system when working with breast cancer survivors. The goal i...

  3. Ulinastatin reduces the resistance of liver cancer cells to epirubicin by inhibiting autophagy.

    Directory of Open Access Journals (Sweden)

    Bin Song

    Full Text Available During chemotherapy, drug resistance caused by autophagy remains a major challenge to successful treatment of cancer patients. The purpose of this study is to show that ulinastatin (UTI, a trypsin inhibitor, could reduce the resistance of liver cancer cells to chemotherapeutic agent epirubicin (EPI. We achieved this conclusion by analyzing the effect of EPI alone or UTI plus EPI on SMMC-7721 and MHCC-LM3 liver cancer cells. We also generated an EPI-resistant liver cancer cell line (MHCC-LM3er cells, and found that UTI could sensitize the LM3er cells to EPI. Autophagy usually functions to protect cancer cells during chemotherapy. Our study showed that UTI inhibited the autophagy induced by EPI in liver cancer cells, which promoted apoptosis, and therefore, reduced the resistance of the cancer cells to EPI. Further studies showed that the UTI-mediated inhibition on autophagy was achieved by inhibiting transcriptional factor nuclear factor-κB (NF-κB signaling pathway. To verify our results in vivo, we injected MHCC-LM3 liver cancer cells or EPI-resistant LM3er cells into mice, and found that EPI could only effectively inhibit the growth of tumor in MHCC-LM3 cell-injected mice, but not in LM3er cell-injected mice. However, when UTI was also administered, the growth of tumor was inhibited in the MHCC-LM3er cell-injected mice as well. Our results suggest that UTI may be used in combination with anti-cancer drugs, such as EPI, to improve the outcome of cancer therapy.

  4. The REDUCE trial: chemoprevention in prostate cancer using a dual 5alpha-reductase inhibitor, dutasteride.

    Science.gov (United States)

    Musquera, Mireia; Fleshner, Neil E; Finelli, Antonio; Zlotta, Alexandre R

    2008-07-01

    Dutasteride, a dual 5alpha-reductase inhibitor, is used in the treatment of benign prostatic hyperplasia (BPH). It reduces serum prostate-specific antigen levels by approximately 50% at 6 months and total prostate volume by 25% after 2 years. Randomized placebo-controlled trials in BPH patients have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate. Side effects occurring with dutasteride are decreased libido, erectile dysfunction, ejaculation disorders and gynecomastia. Preliminary data from placebo-controlled BPH trials have shown a decrease in the detection of prostate cancer in patients treated with dutasteride, although these studies were not designed to look at this issue. Dutasteride differs from finasteride in that it inhibits both isoenzymes of 5alpha-reductase, type I and type II. The landmark Prostate Cancer Prevention Trial at the end of the 7-year study demonstrated a 24.8% reduction in the incidence of prostate cancer in the finasteride group compared with placebo. However, a 25.5% increase in the prevalence of high-grade Gleason tumors has been observed, the clinical significance of which has been debated. Preliminary data suggest a decrease in prostate cancer incidence in dutasteride-treated patients and demonstrate type I alphareductase enzyme expression in prostate cancer. As a result, dutasteride is being investigated for prostate cancer prevention in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which is discussed here. PMID:18588452

  5. 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. PMID:27393623

  6. 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.

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

    International Nuclear Information System (INIS)

    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.

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

    OpenAIRE

    Hyejin Choi; Jianting Sheng; Dingcheng Gao; Fuhai Li; Anna Durrans; Seongho Ryu; Sharrell B. Lee; Navneet Narula; Shahin Rafii; Olivier Elemento; Nasser K. Altorki; Stephen T.C. Wong; Vivek Mittal

    2015-01-01

    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 c...

  9. 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

  10. Integrated transcriptomic and proteomic analysis identifies protein kinase CK2 as a key signaling node in an inflammatory cytokine network in ovarian cancer cells

    Science.gov (United States)

    Kulbe, Hagen; Iorio, Francesco; Chakravarty, Probir; Milagre, Carla S.; Moore, Robert; Thompson, Richard G.; Everitt, Gemma; Canosa, Monica; Montoya, Alexander; Drygin, Denis; Braicu, Ioana; Sehouli, Jalid; Saez-Rodriguez, Julio; Cutillas, Pedro R.; Balkwill, Frances R.

    2016-01-01

    We previously showed how key pathways in cancer-related inflammation and Notch signaling are part of an autocrine malignant cell network in ovarian cancer. This network, which we named the “TNF network”, has paracrine actions within the tumor microenvironment, influencing angiogenesis and the immune cell infiltrate. The aim of this study was to identify critical regulators in the signaling pathways of the TNF network in ovarian cancer cells that might be therapeutic targets. To achieve our aim, we used a systems biology approach, combining data from phospho-proteomic mass spectrometry and gene expression array analysis. Among the potential therapeutic kinase targets identified was the protein kinase Casein kinase II (CK2). Knockdown of CK2 expression in malignant cells by siRNA or treatment with the specific CK2 inhibitor CX-4945 significantly decreased Notch signaling and reduced constitutive cytokine release in ovarian cancer cell lines that expressed the TNF network as well as malignant cells isolated from high grade serous ovarian cancer ascites. The expression of the same cytokines was also inhibited after treatment with CX-4945 in a 3D organotypic model. CK2 inhibition was associated with concomitant inhibition of proliferative activity, reduced angiogenesis and experimental peritoneal ovarian tumor growth. In conclusion, we have identified kinases, particularly CK2, associated with the TNF network that may play a central role in sustaining the cytokine network and/or mediating its effects in ovarian cancer. PMID:26871292

  11. American Indian/Alaska Native cancer policy: systemic approaches to reducing cancer disparities.

    Science.gov (United States)

    Warne, Donald; Kaur, Judith; Perdue, David

    2012-04-01

    Members of American Indian and Alaska Native (AI/AN) tribes have a unique political status in the United States in terms of citizenship, and that political status determines eligibility for certain unique healthcare services. The AI/AN population has a legal right to healthcare services based on treaties, court decisions, acts of Congress, Executive Orders, and other legal bases. Although the AI/AN population has a right to healthcare services, the Indian Health Service (the federal agency responsible for providing healthcare to AI/ANs) is severely underfunded, limiting access to services (including cancer care). In order to overcome distinct cancer health disparities, policy changes will be needed. This paper reviews the historical pattern of AI/AN healthcare and the challenges of the complex care needed from prevention through end-of-life care for cancer.

  12. Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile.

    Science.gov (United States)

    Oliveras-Ferraros, Cristina; Vazquez-Martin, Alejandro; Cuyàs, Elisabet; Corominas-Faja, Bruna; Rodríguez-Gallego, Esther; Fernández-Arroyo, Salvador; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A

    2014-01-01

    Therapeutic interventions based on metabolic inhibitor-based therapies are expected to be less prone to acquired resistance. However, there has not been any study assessing the possibility that the targeting of the tumor cell metabolism may result in unforeseeable resistance. We recently established a pre-clinical model of estrogen-dependent MCF-7 breast cancer cells that were chronically adapted to grow (> 10 months) in the presence of graded, millimolar concentrations of the anti-diabetic biguanide metformin, an AMPK agonist/mTOR inhibitor that has been evaluated in multiple in vitro and in vivo cancer studies and is now being tested in clinical trials. To assess what impact the phenomenon of resistance might have on the metformin-like "dirty" drugs that are able to simultaneously hit several metabolic pathways, we employed the ingenuity pathway analysis (IPA) software to functionally interpret the data from Agilent whole-human genome arrays in the context of biological processes, networks, and pathways. Our findings establish, for the first time, that a "global" targeting of metabolic reprogramming using metformin certainly imposes a great selective pressure for the emergence of new breast cancer cellular states. Intriguingly, acquired resistance to metformin appears to trigger a transcriptome reprogramming toward a metastatic stem-like profile, as many genes encoding the components of the degradome (KLK11, CTSF, FREM1, BACE-2, CASP, TMPRSS4, MMP16, HTRA1), cancer cell migration and invasion factors (TP63, WISP2, GAS3, DKK1, BCAR3, PABPC1, MUC1, SPARCL1, SEMA3B, SEMA6A), stem cell markers (DCLK1, FAK), and key pro-metastatic lipases (MAGL and Cpla2) were included in the signature. Because this convergent activation of pathways underlying tumor microenvironment interactions occurred in low-proliferative cancer cells exhibiting a notable downregulation of the G 2/M DNA damage checkpoint regulators that maintain genome stability (CCNB1, CCNB2, CDC20, CDC25C, AURKA

  13. Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile

    Science.gov (United States)

    Oliveras-Ferraros, Cristina; Vazquez-Martin, Alejandro; Cuyàs, Elisabet; Corominas-Faja, Bruna; Rodríguez-Gallego, Esther; Fernández-Arroyo, Salvador; Martin-Castillo, Begoña; Joven, Jorge; Menendez, Javier A

    2014-01-01

    Therapeutic interventions based on metabolic inhibitor-based therapies are expected to be less prone to acquired resistance. However, there has not been any study assessing the possibility that the targeting of the tumor cell metabolism may result in unforeseeable resistance. We recently established a pre-clinical model of estrogen-dependent MCF-7 breast cancer cells that were chronically adapted to grow (> 10 months) in the presence of graded, millimolar concentrations of the anti-diabetic biguanide metformin, an AMPK agonist/mTOR inhibitor that has been evaluated in multiple in vitro and in vivo cancer studies and is now being tested in clinical trials. To assess what impact the phenomenon of resistance might have on the metformin-like “dirty” drugs that are able to simultaneously hit several metabolic pathways, we employed the ingenuity pathway analysis (IPA) software to functionally interpret the data from Agilent whole-human genome arrays in the context of biological processes, networks, and pathways. Our findings establish, for the first time, that a “global” targeting of metabolic reprogramming using metformin certainly imposes a great selective pressure for the emergence of new breast cancer cellular states. Intriguingly, acquired resistance to metformin appears to trigger a transcriptome reprogramming toward a metastatic stem-like profile, as many genes encoding the components of the degradome (KLK11, CTSF, FREM1, BACE-2, CASP, TMPRSS4, MMP16, HTRA1), cancer cell migration and invasion factors (TP63, WISP2, GAS3, DKK1, BCAR3, PABPC1, MUC1, SPARCL1, SEMA3B, SEMA6A), stem cell markers (DCLK1, FAK), and key pro-metastatic lipases (MAGL and Cpla2) were included in the signature. Because this convergent activation of pathways underlying tumor microenvironment interactions occurred in low-proliferative cancer cells exhibiting a notable downregulation of the G2/M DNA damage checkpoint regulators that maintain genome stability (CCNB1, CCNB2, CDC20, CDC25C

  14. 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

    OpenAIRE

    Nicolson, Garth L.; Robert Settineri

    2011-01-01

    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 impr...

  15. Reducing the Human Burden of Breast Cancer: Advanced Radiation Therapy Yields Improved Treatment Outcomes.

    Science.gov (United States)

    Currey, Adam D; Bergom, Carmen; Kelly, Tracy R; Wilson, J Frank

    2015-01-01

    Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x-rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of treatment benefit, as well as patient and biological factors that confer an increased recurrence risk, have allowed radiation oncologists to better tailor treatment decisions to individual patients. Furthermore, significant technological advances have occurred that have reduced the acute and long-term toxicity of radiation treatment. These advances continue to reduce the human burden of breast cancer. It is important for radiation oncologists and nonradiation oncologists to understand these advances, so that patients are appropriately educated about the risks and benefits of this important treatment modality.

  16. Tamoxifen's protection against breast cancer recurrence is not reduced by concurrent use of the SSRI citalopram

    DEFF Research Database (Denmark)

    Lash, T L; Pedersen, L; Cronin-Fenton, D;

    2008-01-01

    serotonin reuptake inhibitors (SSRI), so these widely used drugs - when taken concurrently - may reduce tamoxifen's prevention of breast cancer recurrence. We studied citalopram use in 184 cases of breast cancer recurrence and 184 matched controls without recurrence after equivalent follow-up. Cases and...... prescription databases from the National Health Service. Seventeen cases (9%) and 21 controls (11%) received at least one prescription for the SSRI citalopram while taking tamoxifen (adjusted conditional odds ratio=0.85, 95% confidence interval=0.42, 1.7). We also observed no reduction of tamoxifen...... effectiveness among regular citalopram users (>or=30% overlap with tamoxifen use). These results suggest that concurrent use of citalopram does not reduce tamoxifen's prevention of breast cancer recurrence....

  17. Apples to origins: Identifying brain tumor stem cell genes by comparing transcriptomes of normal and cancer stem cells

    OpenAIRE

    Wortham, Matthew; Yan, Hai

    2012-01-01

    The mechanisms whereby medulloblastoma stem cells coordinate tumor propagation are poorly understood. Utilizing microarray analysis, Corno and colleagues draw parallels and distinctions between medulloblastoma stem cells from the Ptch+/− mouse and normal neural stem cells, identifying Ebf3 as a cancer stem cell-specific transcript critical for tumor growth.

  18. 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

    Whereas genome sequencing defines the genetic potential of an organism, transcript sequencing defines the utilization of this potential and links the genome with most areas of biology. To exploit the information within the human genome in the fight against cancer, we have deposited some two milli...

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    H. Ross-Adams

    2015-09-01

    Interpretation: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

  1. Transcriptome analysis of individual stromal cell populations identifies stroma-tumor crosstalk in mouse lung cancer model.

    Science.gov (United States)

    Choi, Hyejin; Sheng, Jianting; Gao, Dingcheng; Li, Fuhai; Durrans, Anna; Ryu, Seongho; Lee, Sharrell B; Narula, Navneet; Rafii, Shahin; Elemento, Olivier; Altorki, Nasser K; Wong, Stephen T C; Mittal, Vivek

    2015-02-24

    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. PMID:25704820

  2. 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.

  3. 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.

  4. Candidate Antimetastasis Drugs Suppress the Metastatic Capacity of Breast Cancer Cells by Reducing Membrane Fluidity.

    Science.gov (United States)

    Zhao, Weina; Prijic, Sara; Urban, Bettina C; Tisza, Michael J; Zuo, Yan; Li, Lin; Tan, Zhi; Chen, Xiaoling; Mani, Sendurai A; Chang, Jeffrey T

    2016-04-01

    Despite the high mortality from metastatic cancer, therapeutic targets to prevent metastasis are limited. Efforts to identify genetic aberrations that predispose tumors to metastasis have been mostly unsuccessful. To understand the nature of candidate targets for metastatic disease, we performed an in silico screen to identify drugs that can inhibit a gene expression signature associated with epithelial-mesenchymal transition (EMT). Compounds discovered through this method, including those previously identified, appeared to restrict metastatic capacity through a common mechanism, the ability to modulate the fluidity of cell membranes. Treatment of breast cancer cell lines with the putative antimetastasis agents reduced membrane fluidity, resulting in decreased cell motility, stem cell-like properties, and EMT in vitro, and the drugs also inhibited spontaneous metastasis in vivo When fluidity was unchanged, the antimetastasis compounds could no longer restrict metastasis, indicating a causal association between fluidity and metastasis. We further demonstrate that fluidity can be regulated by cellular cholesterol flux, as the cholesterol efflux channel ABCA1 potentiated metastatic behaviors in vitro and in vivo The requirement for fluidity was further supported by the finding in breast cancer patients that ABCA1 was overexpressed in 41% of metastatic tumors, reducing time to metastasis by 9 years. Collectively, our findings reveal increased membrane fluidity as a necessary cellular feature of metastatic potential that can be controlled by many currently available drugs, offering a viable therapeutic opportunity to prevent cancer metastasis. Cancer Res; 76(7); 2037-49. ©2016 AACR. PMID:26825169

  5. The anthelmintic drug niclosamide induces apoptosis, impairs metastasis and reduces immunosuppressive cells in breast cancer model.

    Directory of Open Access Journals (Sweden)

    Tinghong Ye

    Full Text Available Breast carcinoma is the most common female cancer with considerable metastatic potential. Discovery of new therapeutic approaches for treatment of metastatic breast cancer is still needed. Here, we reported our finding with niclosamide, an FDA approved anthelmintic drug. The potency of niclosamide on breast cancer was assessed in vitro and in vivo. In this investigation, we found that niclosamide showed a dramatic growth inhibition against breast cancer cell lines and induced apoptosis of 4T1 cells in a dose-dependent manner. Further, Western blot analysis demonstrated the occurrence of its apoptosis was associated with activation of Cleaved caspases-3, down-regulation of Bcl-2, Mcl-1 and Survivin. Moreover, niclosamide blocked breast cancer cells migration and invasion, and the reduction of phosphorylated STAT3(Tyr705, phosphorylated FAK(Tyr925 and phosphorylated Src(Tyr416 were also observed. Furthermore, in our animal experiments, intraperitoneal administration of 20 mg/kg/d niclosamide suppressed 4T1 tumor growth without detectable toxicity. Histological and immunohistochemical analyses revealed a decrease in Ki67-positive cells, VEGF-positive cells and microvessel density (MVD and an increase in Cleaved caspase-3-positive cells upon niclosamide. Notably, niclosamide reduced the number of myeloid-derived suppressor cells (MDSCs in tumor tissues and blocked formation of pulmonary metastases. Taken together, these results demonstrated that niclosamide may be a promising candidate for breast cancer.

  6. Application of chemokine receptor antagonist with stents reduces local inflammation and suppresses cancer growth.

    Science.gov (United States)

    Mao, Ai-Wu; Jiang, Ting-Hui; Sun, Xian-Jun; Peng, Jian

    2015-11-01

    Severe pain and obstructive jaundice resulting from invasive cholangiocarcinoma or pancreatic carcinoma can be alleviated by implantation of biliary and duodenal stents. However, stents may cause local inflammation to have an adverse effect on the patients' condition and survival. So far, no efficient approaches have been applied to prevent the occurrence of stents-related inflammation. Here, we reported significantly higher levels of serum stromal cell-derived factor 1 (SDF-1) in the patients that developed stents-associated inflammation. A higher number of inflammatory cells have been detected in the cancer close to stent in the patients with high serum SDF-1. Since chemokine plays a pivotal role in the development of inflammation, we implanted an Alzet osmotic pump with the stents to gradually release AMD3100, a specific inhibitor binding of SDF-1 and its receptor C-X-C chemokine receptor 4 (CXCR4), at the site of stents in mice that had developed pancreatic cancer. We found that AMD3100 significantly reduced local inflammation and significantly inhibited cancer cell growth, resulting in improved survival of the mice that bore cancer. Moreover, the suppression of cancer growth may be conducted through modulation of CyclinD1, p21, and p27 in the cancer cells. Together, these data suggest that inhibition of chemokine signaling at the site of stents may substantially improve survival through suppression of stent-related inflammation and tumor growth.

  7. p62/IMP2 stimulates cell migration and reduces cell adhesion in breast cancer

    Science.gov (United States)

    Li, Yang; Francia, Giulio; Zhang, Jian-Ying

    2015-01-01

    p62/IMP2 is an oncofetal protein that is overexpressed in several types of cancer, and is a member of the family of insulin-like growth factor 2 mRNA binding proteins. We previously reported that high levels of p62/IMP2 autoantibody are present in sera from cancer patients, compared to healthy individuals. Here, we report the overexpression of p62/IMP2 in tumor tissues of 72 out of 104 cases of human breast cancer, and high levels of p62/IMP2 autoantibody in patients’ sera (in 63 out of 216 cases). To explore the role of p62/IMP2 in breast cancer progression, we generated p62/IMP2 transfected variants of two human breast cancer cell lines: MDA-MB-231 and LM2-4. Using in vitro assays we found that overexpression of p62/IMP2 can increase cell migration, and reduce cell adhesion to extracellular matrix (ECM) proteins. A Human Extracellular Matrix and Adhesion Molecules qPCR array was performed with our generated variants, and it identified a group of mRNAs whose expression was altered with p62/IMP2 overexpression, including connective tissue growth factor (CTGF) mRNA – which we show to be a p62/IMP2 binding partner. Overall, our results provide new insights into the molecular mechanism by which p62/IMP2 can contribute to breast cancer progression. PMID:26416451

  8. Reduced methylation of PFKFB3 in cancer cells shunts glucose towards the pentose phosphate pathway.

    Science.gov (United States)

    Yamamoto, Takehiro; Takano, Naoharu; Ishiwata, Kyoko; Ohmura, Mitsuyo; Nagahata, Yoshiko; Matsuura, Tomomi; Kamata, Aki; Sakamoto, Kyoko; Nakanishi, Tsuyoshi; Kubo, Akiko; Hishiki, Takako; Suematsu, Makoto

    2014-03-17

    Haem oxygenase (HO)-1/carbon monoxide (CO) protects cancer cells from oxidative stress, but the gas-responsive signalling mechanisms remain unknown. Here we show using metabolomics that CO-sensitive methylation of PFKFB3, an enzyme producing fructose 2,6-bisphosphate (F-2,6-BP), serves as a switch to activate phosphofructokinase-1, a rate-limiting glycolytic enzyme. In human leukaemia U937 cells, PFKFB3 is asymmetrically di-methylated at R131 and R134 through modification by protein arginine methyltransferase 1. HO-1 induction or CO results in reduced methylation of PFKFB3 in varied cancer cells to suppress F-2,6-BP, shifting glucose utilization from glycolysis toward the pentose phosphate pathway. Loss of PFKFB3 methylation depends on the inhibitory effects of CO on haem-containing cystathionine β-synthase (CBS). CBS modulates remethylation metabolism, and increases NADPH to supply reduced glutathione, protecting cells from oxidative stress and anti-cancer reagents. Once the methylation of PFKFB3 is reduced, the protein undergoes polyubiquitination and is degraded in the proteasome. These results suggest that the CO/CBS-dependent regulation of PFKFB3 methylation determines directional glucose utilization to ensure resistance against oxidative stress for cancer cell survival.

  9. Endoscopic ultrasound-guided coeliac plexus neurolysis to reduce pain in patients with pancreatic cancer

    DEFF Research Database (Denmark)

    Vilmann, Andreas Slot; Karstensen, John Gésdal; Cherciu, Irina;

    2014-01-01

    Pain is among the most common symptoms in patients with pancreatic cancer and up to 80% require analgesics, most often as opioids. Unfortunately the analgesic effect is frequently insufficient, and increasing doses are required, resulting in unpleasant side effects. Endoscopic ultrasound......-guided neurolysis is a well established method to alleviate or reduce pain due to pancreatic cancer with a documented effect in 80% of patients. The aim of this review is to draw attention to endoscopic ultrasound-guided neurolysis and to discuss its potential which may not be fully utilized....

  10. Dietary cholesterol deprivation improves survival and reduces incidence of metastatic colon cancer in dimethylhydrazine-pretreated rats.

    OpenAIRE

    Cruse, J P; Lewin, M. R.; Clark, C G

    1982-01-01

    Cholesterol feeding of rats with colon cancer induced by dimethylhydrazine results in reduced survival and an increased incidence of metastatic colon cancer. As cholesterol may be implicated in the induction or maintenance of the metastatic process, an experiment was designed to determine whether rats with colon cancer would benefit from the removal of cholesterol from the diet. Female Wistar rats were treated with a colon cancer-inducing regimen of dimethylhydrazine (40 mg/kg/week for 10 wee...

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

    Science.gov (United States)

    Martins, Murillo L.; Ignazzi, Rosanna; Eckert, Juergen; Watts, Benjamin; Kaneno, Ramon; Zambuzzi, Willian F.; Daemen, Luke; Saeki, Margarida J.; Bordallo, Heloisa N.

    2016-03-01

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-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 with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. From these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier design is potentially safer to healthy cells.

  12. Peanut consumption and reduced risk of colorectal cancer in women: A prospective study in Taiwan

    Institute of Scientific and Technical Information of China (English)

    Chih-Ching Yeh; San-Lin You; Chien-Jen Chen; Fung-Chang Sung

    2006-01-01

    AIM: To examine whether peanut consumption is associated with a reduced risk of colorectal cancer in a prospective cohort with a 10-year follow-up.METHODS: In 1990-1992, residents (12026 men and 11917 women aged 30 to 65 years) in 7 townships,Taiwan, were interviewed and recruited into a cancerscreening cohort and annually followed up. Colorectal cancer cases in this cohort were identified from cancer registry and death certificates. Incidence rates of this disease by the end of 2001 were calculated by gender for the primary study variable and covariates. The dietary intake was assessed by means of weekly food frequency measures, including frequently consumed food groups and folk dishes including sweet potato, bean products,peanut products, pickled foodstuffs, nitrated or smoked foodstuffs.RESULTS: During the study period, 107 new colorectal cancer cases (68 men and 39 women) were confirmed.The multivariate Cox's proportional hazard model showed that the relative risk (RR) of peanut consumption was 0.73[95% confidence interval (CI) = 0.44-1.21] for men and 0.42 (95% CI = 0.21-0.84) for women. However, frequent intake of pickled foodstuffs was harmful for women (RR=2.15, 95% CI=0.99-4.65). The risk of colorectal cancer was also elevated among cigarette smokers but not significant (P< 0.05).CONCLUSION: This study suggests that frequent intake of peanut and its products may reduce colorectal cancer risk in women, demonstrating the anti-proliferating effect of peanut intake.

  13. 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.

  14. Fruit Consumption Reduces the Risk of Esophageal Cancer in Yanting, People's Republic of China.

    Science.gov (United States)

    Song, Qingkun; Zhao, Lin; Li, Jun; Ren, Jun

    2015-05-01

    This study aimed to investigate the contribution of fruit and family history to esophageal cancer, among residents with abnormal esophagus discovered in screening. The study was a frequency-matched case-control design in groups of normal esophagus, abnormal esophagus but not carcinoma, and esophageal squamous cell carcinoma. Odds ratio (OR) was estimated by unconditional logistic regression. Fruit intake (OR = 0.19, 95% CI = 0.06-0.56) and positive family history of esophageal cancer (OR = 3.87, 95% CI = 1.41-10.63) were associated with esophageal cancer compared to individuals with abnormal conditions of the esophagus. In individuals who consumed fruits at least once per week, the OR for family cancer history is reduced to a nonsignificant level (OR = 1.06, 95% CI = 0.07-15.91). In the individuals with abnormal esophagus at screening, fruit intake was possibly protective against esophageal cancer, even in the ones with positive family history. Local public health strategies should focus on the improvement in fruit intake.

  15. Reducing the weight of cancer: mechanistic targets for breaking the obesity-carcinogenesis link.

    Science.gov (United States)

    Hursting, Stephen D; Lashinger, Laura M; Wheatley, Karrie W; Rogers, Connie J; Colbert, Lisa H; Nunez, Nomeli P; Perkins, Susan N

    2008-08-01

    The prevalence of obesity, an established epidemiologic risk factor for many cancers, has risen steadily for the past several decades in the US. The increasing rates of obesity among children are especially alarming and suggest continuing increases in the rates of obesity-related cancers for many years to come. Unfortunately, the mechanisms underlying the association between obesity and cancer are not well understood. In particular, the effects on the carcinogenesis process and mechanistic targets of interventions that modulate energy balance, such as reduced-calorie diets and physical activity, have not been well characterized. The purpose of this review is to provide a strong foundation for the translation of mechanism-based research in this area by describing key animal and human studies of energy balance modulations involving diet or physical activity and by focusing on the interrelated pathways affected by alterations in energy balance. Particular attention is placed on signaling through the insulin and insulin-like growth factor-1 receptors, including components of the Akt and mammalian target of rapamycin (mTOR) signaling pathways downstream of these growth factor receptors. These pathways have emerged as potential targets for disrupting the obesity-cancer link. The ultimate goal of this work is to provide the missing mechanistic information necessary to identify targets for the prevention and control of cancers related to or caused by excess body weight.

  16. 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

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

    OpenAIRE

    Flores Juana M; Moreno-Bueno Gema; Cerutti Camilla; Pérez-Gómez Eduardo; Mira Emilia; Andradas Clara; Caffarel María M; García-Real Isabel; Palacios José; Mañes Santos; Guzmán Manuel; Sánchez Cristina

    2010-01-01

    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 whe...

  18. Do high risk patients alter their lifestyle to reduce risk of colorectal cancer?

    OpenAIRE

    Tarr, Gregory P; Crowley, Andrew; John, Rhys; Kok, Jonathan B; Lee, Ho-Nam L; Mustafa, Hasif; Sii, Kia M; Smith, Rebecca; Son, Sung-Eun Q; Weaver, Lauren J; Cameron, Claire; Dockerty, John D.; Schultz, Michael; Murray, Iain A.

    2014-01-01

    Background Colorectal cancer (CRC) may be reduced by healthy lifestyle behaviours. We determined the extent of self-reported lifestyle changes in people at increased risk of CRC, and the association of these reports with anxiety, risk and knowledge-based variables. Methods We randomly selected 250 participants who had undergone surveillance colonoscopy for family history of CRC. A telephone interview was conducted, recording demographics and family history. Self-reported lifestyle change due ...

  19. Inhibition of xanthine oxidase reduces wasting and improves outcome in a rat model of cancer cachexia.

    Science.gov (United States)

    Springer, Jochen; Tschirner, Anika; Hartman, Kai; Palus, Sandra; Wirth, Eva K; Ruis, Silvia Busquets; Möller, Nadine; von Haehling, Stephan; Argiles, Josep M; Köhrle, Josef; Adams, Volker; Anker, Stefan D; Doehner, Wolfram

    2012-11-01

    Cachexia is a common co-morbidity in cancer occurring in up to 80% of patients depending on the type of cancer. Uric acid (UA), the end-product of the purine metabolism, is elevated in cachexia due to tissue wasting and upregulated xanthine oxidase (XO) activity. High serum UA levels indicate increased XO-dependent production of oxygen free radicals (reactive oxygen species; ROS) and correlate with metabolic illness and poor survival. We hypothesized that XO-inhibition might reduce inflammatory signals accounting for tissue wasting and improve survival in experimental cancer cachexia. Animals were inoculated intraperitoneally with AH-130 hepatoma cells and treated with two XO-inhibitors: allopurinol [Allo, low (LD) and high dose (HD) 4 and 40 mg/kg/d] and its more effective active metabolite oxypurinol (Oxy, 4 and 40 mg/kg/d) or placebo for 15 days. Weight loss and tissue wasting of both fat and lean tissue (assessed by NMR-scanning) was reduced by both LD and HD Allo and LD-Oxy, but not by HD-Oxy. A robust induction of XO-activity for generation of reactive oxygen species was seen in the placebo group (assessed by electron paramagnetic spectroscopy), which was reduced by XO-inhibition. Increased ROS induced cytokine signaling, proteolytic activity and tissue degradation were all attenuated by XO inhibition. Survival was significantly and dose dependently improved. Food intake and spontaneous locomotor activity were higher, indicating a higher quality of life. Inhibition of XO can reduce tissue wasting and improve survival in cancer cachexia and clearly clinical studies are needed.

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

    Science.gov (United States)

    Khan, Merajuddin; Khan, Mujeeb; Al-Marri, Abdulhadi H; Al-Warthan, Abdulrahman; Alkhathlan, Hamad Z; Siddiqui, Mohammed Rafiq H; Nayak, Vadithe Lakshma; Kamal, Ahmed; Adil, Syed F

    2016-01-01

    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 nano composites (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. PMID:27022256

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

    International Nuclear Information System (INIS)

    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

  2. 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.

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

    Science.gov (United States)

    Khan, Merajuddin; Khan, Mujeeb; Al-Marri, Abdulhadi H; Al-Warthan, Abdulrahman; Alkhathlan, Hamad Z; Siddiqui, Mohammed Rafiq H; Nayak, Vadithe Lakshma; Kamal, Ahmed; Adil, Syed F

    2016-01-01

    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 nano composites (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.

  4. 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.

  5. 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.

  6. Surveillance recommendations in reducing risk of and optimally managing breast cancer-related lymphedema.

    Science.gov (United States)

    Ostby, Pamela L; Armer, Jane M; Dale, Paul S; Van Loo, Margaret J; Wilbanks, Cassie L; Stewart, Bob R

    2014-01-01

    Breast cancer survivors are at increased risk for the development of breast cancer-related lymphedema (BCRL), a chronic, debilitating, and disfiguring condition that is progressive and requires lifelong self-management of symptoms. It has been reported that over 40% of the 2.5 million breast cancer survivors in the United States may meet the criteria for BCRL during their lifetimes. Ongoing surveillance, beginning with pre-operative assessment, has been effective in identifying subclinical lymphedema (LE). A prospective model for surveillance is necessary in order to detect BCRL at an early stage when there is the best chance to reduce risk or slow progression. Physical methods for monitoring and assessment, such as circumferential arm measures, perometry, bioimpedance; exercise programs; prophylactic and early-intervention compression garments; and referral for complete decongestive therapy are all interventions to consider in the development of a BCRL surveillance program. In addition, supportive-educative programs and interactive engagement for symptom self-management should also be implemented. The importance of interdisciplinary collaboration is integral to the success of an effective personalized medicine program in breast cancer-related lymphedema surveillance. PMID:25563360

  7. Surveillance Recommendations in Reducing Risk of and Optimally Managing Breast Cancer-Related Lymphedema

    Directory of Open Access Journals (Sweden)

    Pamela L. Ostby

    2014-08-01

    Full Text Available Breast cancer survivors are at increased risk for the development of breast cancer-related lymphedema (BCRL, a chronic, debilitating, and disfiguring condition that is progressive and requires lifelong self-management of symptoms. It has been reported that over 40% of the 2.5 million breast cancer survivors in the United States may meet the criteria for BCRL during their lifetimes. Ongoing surveillance, beginning with pre-operative assessment, has been effective in identifying subclinical lymphedema (LE. A prospective model for surveillance is necessary in order to detect BCRL at an early stage when there is the best chance to reduce risk or slow progression. Physical methods for monitoring and assessment, such as circumferential arm measures, perometry, bioimpedance; exercise programs; prophylactic and early-intervention compression garments; and referral for complete decongestive therapy are all interventions to consider in the development of a BCRL surveillance program. In addition, supportive-educative programs and interactive engagement for symptom self-management should also be implemented. The importance of interdisciplinary collaboration is integral to the success of an effective personalized medicine program in breast cancer-related lymphedema surveillance.

  8. Housework reduces all-cause and cancer mortality in Chinese men.

    Directory of Open Access Journals (Sweden)

    Ruby Yu

    Full Text Available BACKGROUND: Leisure time physical activity has been extensively studied. However, the health benefits of non-leisure time physical activity, particular those undertaken at home on all-cause and cancer mortality are limited, particularly among the elderly. METHODS: We studied physical activity in relation to all-cause and cancer mortality in a cohort of 4,000 community-dwelling elderly aged 65 and older. Leisure time physical activity (sport/recreational activity and lawn work/yard care/gardening and non-leisure time physical activity (housework, home repairs and caring for another person were self-reported on the Physical Activity Scale for the Elderly. Subjects with heart diseases, stroke, cancer or diabetes at baseline were excluded (n = 1,133. RESULTS: Among the 2,867 subjects with a mean age of 72 years at baseline, 452 died from all-cause and 185 died from cancer during the follow-up period (2001-2012. With the adjustment for age, education level and lifestyle factors, we found an inverse association between risk of all-cause mortality and heavy housework among men, with the adjusted hazard ratio (HR of 0.72 (95%CI = 0.57-0.92. Further adjustment for BMI, frailty index, living arrangement, and leisure time activity did not change the result (HR = 0.71, 95%CI = 0.56-0.91. Among women, however, heavy housework was not associated with all-cause mortality. The risk of cancer mortality was significantly lower among men who participated in heavy housework (HR = 0.52, 95%CI = 0.35-0.78, whereas among women the risk was not significant. Men participated in light housework also were at lower risk of cancer mortality than were their counterparts, however, the association was not significant. Leisure time physical activity was not related to all-cause or cancer mortality in either men or women. CONCLUSION: Heavy housework is associated with reduced mortality and cancer deaths over a 9-year period. The underlying mechanism needs

  9. Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2016-08-01

    This retrospective cohort study investigated whether metformin may reduce gastric cancer risk by using the reimbursement databases of the Taiwan's National Health Insurance. Patients with type 2 diabetes diagnosed during 1999-2005 and newly treated with metformin (n=287971, "ever users of metformin") or other antidiabetic drugs (n=16217, "never users of metformin") were followed until December 31, 2011. The effect of metformin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Results showed that the respective numbers of incident gastric cancer in ever and never users were 759 (0.26%) and 89 (0.55%), with respective incidences of 55.26 and 122.53 per 100,000 person-years. The overall hazard ratio (95% confidence intervals) of 0.448 (0.359-0.558) suggested a significantly lower risk among ever users. In tertile analyses, hazard ratios (95% confidence intervals) for the first (<21.47 months), second (21.47-45.97 months) and third (>45.97 months) tertile of cumulative duration was 0.973 (0.773-1.224), 0.422 (0.331-0.537) and 0.120 (0.090-0.161), respectively, while compared to never users. In conclusion, metformin significantly reduces gastric cancer risk, especially when the cumulative duration is more than approximately 2 years. PMID:27587088

  10. Contralateral risk reducing mastectomy in patients with sporadic breast cancer. Benefits and hazards.

    Science.gov (United States)

    Boccardo, C; Gentilini, O

    2016-07-01

    During the last years an improving outcome of breast conserving surgery was observed along with the availability of diagnostic procedures allowing early diagnosis. Nevertheless, women with breast cancer are more frequently requesting a radical approach comprising contralateral mastectomy even if they do not have a demonstrated increased genetic risk. In this paper we reviewed the main reasons patients ask for aggressive preventive surgery, the perceived and the real risks of developing contralateral breast cancer, and the potential, if any, survival benefits along with the hazards associated to contralateral risk reducing mastectomy. A respectful management should be given to these women within a multi-disciplinary team. Psychological support is highly encouraged cope fears and uncertainties but treating physicians should provide patients with comprehensive and unbiased data to take the best decision for the single person. Physicians should also give clear information on the benefits of adjuvant therapies which are reducing the incidence of contralateral breast cancer and also of the possible influences of healthy lifestyle (weight control, physical activity, diet) as effective preventive methods. PMID:27189832

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

    International Nuclear Information System (INIS)

    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 Ptrend ≤ 0.04), but not with other subtypes (all Ptrend > 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 Ptrend ≤ 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 (Phomogeneity = 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

  12. Neoadjuvant chemotherapy for locally advanced cervical cancer reduces surgical risks and lymph-vascular space involvement

    Institute of Scientific and Technical Information of China (English)

    Yue Wang; Guang Wang; Li-Hui Wei; Ling-Hui Huang; Jian-Liu Wang; Shi-Jun Wang; Xiao-Ping Li

    2011-01-01

    Neoadjuvant chemotherapy (NACT),which can reduce the size and therefore increase the resectability of tumors,has recently evolved as a treatment for locally advanced cervical cancer.NACT has been reported to decrease the risk of pathologic factors related to prognosis of cervical cancer.To further assess the effects of NACT on surgery and the pathologic characteristics of cervicat cancer,we reviewed 110 cases of locally advanced cervical cancer treated with radical hysterectomy with or without NACT at the People's Hospital of Peking University between January 2006 and December 2010.Of 110 patients,68 underwent platinum-based NACT prior to surgery (NACT group) and 42 underwent pdmary surgery treatment (PST group).Our results showed 48 of 68 (70.6%) patients achieved a complete response or partial response to NACT.Estimated blood loss,operation time,and number of removed lymph nodes during surgery,as well as complication rates during and after surgery were not significantly different between the NACT group and the PST group.The rates of deep stromal invasion,positive parametria,positive surgical vaginal margins,and lymph node metastasis were not significantly different between the two groups.However,the rate of lymph-vascular space involvement (LVSI) was significantly lower in the NACT group than in the PST group (P = 0.021).In addition,the response rate of NACT was significantly higher in the patients with chemotherapeutic drugs administrated via artery than via vein.Our results suggest that NACT is a safe and effective treatment for locally advanced cervical cancer and significantly decreases the rate of LVSI.

  13. Pancratistatin selectively targets cancer cell mitochondria and reduces growth of human colon tumor xenografts.

    Science.gov (United States)

    Griffin, Carly; Karnik, Aditya; McNulty, James; Pandey, Siyaram

    2011-01-01

    The naturally occurring Amaryllidaceae alkaloid pancratistatin exhibits potent apoptotic activity against a large panel of cancer cells lines and has an insignificant effect on noncancerous cell lines, although with an elusive cellular target. Many current chemotherapeutics induce apoptosis via genotoxic mechanisms and thus have low selectivity. The observed selectivity of pancratistatin for cancer cells promoted us to consider the hypothesis that this alkaloid targets cancer cell mitochondria rather than DNA or its replicative machinery. In this study, we report that pancratistatin decreased mitochondrial membrane potential and induced apoptotic nuclear morphology in p53-mutant (HT-29) and wild-type p53 (HCT116) colorectal carcinoma cell lines, but not in noncancerous colon fibroblast (CCD-18Co) cells. Interestingly, pancratistatin was found to be ineffective against mtDNA-depleted (ρ(0)) cancer cells. Moreover, pancratistatin induced cell death in a manner independent of Bax and caspase activation, and did not alter β-tubulin polymerization rate nor cause double-stranded DNA breaks. For the first time we report the efficacy of pancratistatin in vivo against human colorectal adenocarcinoma xenografts. Intratumor administration of pancratistatin (3 mg/kg) caused significant reduction in the growth of subcutaneous HT-29 tumors in Nu/Nu mice (n = 6), with no apparent toxicity to the liver or kidneys as indicated by histopathologic analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Altogether, this work suggests that pancratistatin may be a novel mitochondria-targeting compound that selectively induces apoptosis in cancer cells and significantly reduces tumor growth. PMID:21220492

  14. Reduced Popdc3 expression correlates with high risk and poor survival in patients with gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Deng Luo; Ming-Liang Lu; Gong-Fang Zhao; Hua Huang; Meng-Yao Zheng; Jiang Chang; Lin Lv

    2012-01-01

    AIM:To investigate the expression of Popeye domain containing 3 (Popdc3) and its correlation with clinicopathological features and prognosis of gastric cancer.METHODS:The method of immunohistochemistry was used to investigate the expression of Popdc3 in 306 cases of human gastric cancer and 84 noncancerous gastric tissues.Simultaneously,the relationship between Popdc3 expression and the survival of the patients was retrospectively analyzed.RESULTS:Popdc3 was detected in 72 (85.71%) of 84 human nontumor mucosa.High expression of Popdc3 protein was detected in 78 (25.49%) of 306 human gastric cancer cases,and low expression was detected in 228 (74.51%).Low expression of Popdc3 correlated with depth of invasion (P < 0.0001),regional lymph nodes (P < 0.0001) and distant metastasis (P =0.02),and tumor,nodes,metastasis (TNM) stages (P< 0.0001).On multivariate analysis,only the patient's gender,regional lymph node metastasis,distant metastasis,TNM stages,and the expression of Popdc3 were independent prognostic factors in patients with gastric cancer.The Kaplan-Meier plot showed that low Popdc3 expression had a much more significant effect on the survival of those patients with early-stage tumors (x2 =104.741,P < 0.0001),with a > 51.9% reduction in the three-year survival compared with high Popdc3 expression.In late stages,the difference was also significant (x2 =5.930,P =0.015),with a 32.6% reduction in the three-year survival.CONCLUSION:Reduced expression of Popdc3 may play a significant role in the carcinogenesis and progression of gastric cancer.Popdc3 may be an independent prognostic factor.

  15. Vegan proteins may reduce risk of cancer, obesity, and cardiovascular disease by promoting increased glucagon activity.

    Science.gov (United States)

    McCarty, M F

    1999-12-01

    Amino acids modulate the secretion of both insulin and glucagon; the composition of dietary protein therefore has the potential to influence the balance of glucagon and insulin activity. Soy protein, as well as many other vegan proteins, are higher in non-essential amino acids than most animal-derived food proteins, and as a result should preferentially favor glucagon production. Acting on hepatocytes, glucagon promotes (and insulin inhibits) cAMP-dependent mechanisms that down-regulate lipogenic enzymes and cholesterol synthesis, while up-regulating hepatic LDL receptors and production of the IGF-I antagonist IGFBP-1. The insulin-sensitizing properties of many vegan diets--high in fiber, low in saturated fat--should amplify these effects by down-regulating insulin secretion. Additionally, the relatively low essential amino acid content of some vegan diets may decrease hepatic IGF-I synthesis. Thus, diets featuring vegan proteins can be expected to lower elevated serum lipid levels, promote weight loss, and decrease circulating IGF-I activity. The latter effect should impede cancer induction (as is seen in animal studies with soy protein), lessen neutrophil-mediated inflammatory damage, and slow growth and maturation in children. In fact, vegans tend to have low serum lipids, lean physiques, shorter stature, later puberty, and decreased risk for certain prominent 'Western' cancers; a vegan diet has documented clinical efficacy in rheumatoid arthritis. Low-fat vegan diets may be especially protective in regard to cancers linked to insulin resistance--namely, breast and colon cancer--as well as prostate cancer; conversely, the high IGF-I activity associated with heavy ingestion of animal products may be largely responsible for the epidemic of 'Western' cancers in wealthy societies. Increased phytochemical intake is also likely to contribute to the reduction of cancer risk in vegans. Regression of coronary stenoses has been documented during low-fat vegan diets

  16. 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

  17. 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

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti...... with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. From these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier...

  18. 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.

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

    Science.gov (United States)

    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, Cancers 2015, 7 1886 these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer. PMID:26393651

  20. Reduced repair of 8-hydroxyguanine in the human breast cancer cell line, HCC1937

    Directory of Open Access Journals (Sweden)

    Trzeciak Andrzej R

    2006-12-01

    Full Text Available Abstract Background Breast cancer is the second leading cause of cancer deaths in women in the United States. Although the causes of this disease are incompletely understood, oxidative DNA damage is presumed to play a critical role in breast carcinogenesis. A common oxidatively induced DNA lesion is 8-hydroxyguanine (8-OH-Gua, which has been implicated in carcinogenesis. The aim of this study was to investigate the ability of HCC1937 and MCF-7 breast cancer cell lines to repair 8-OH-Gua relative to a nonmalignant human mammary epithelial cell line, AG11134. Methods We used oligonucleotide incision assay to analyze the ability of the two breast cancer cell lines to incise 8-OH-Gua relative to the control cell line. Liquid chromatography/mass spectrometry (LC/MS was used to measure the levels of 8-OH-Gua as its nucleoside, 8-OH-dG in the cell lines after exposure to H2O2 followed by 30 min repair period. Protein expression levels were determined by Western blot analysis, while the hOGG1 mRNA levels were analyzed by RT-PCR. Complementation of hOGG1 activity in HCC1937 cells was assessed by addition of the purified protein in the incision assay, and in vivo by transfection of pFlagCMV-4-hOGG1. Clonogenic survival assay was used to determine sensitivity after H2O2-mediated oxidative stress. Results We show that the HCC1937 breast cancer cells have diminished ability to incise 8-OH-Gua and they accumulate higher levels of 8-OH-dG in the nuclear genome after H2O2 treatment despite a 30 min repair period when compared to the nonmalignant mammary cells. The defective incision of 8-OH-Gua was consistent with expression of undetectable amounts of hOGG1 in HCC1937 cells. The reduced incision activity was significantly stimulated by addition of purified hOGG1. Furthermore, transfection of pFlagCMV-4-hOGG1 in HCC1937 cells resulted in enhanced incision of 8-OH-Gua. HCC1937 cells are more sensitive to high levels of H2O2 and have up-regulated SOD1 and SOD2

  1. 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 messe

  2. 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

  3. High-resolution diffusion tensor imaging of prostate cancer using a reduced FOV technique

    Energy Technology Data Exchange (ETDEWEB)

    Reischauer, Carolin, E-mail: reischauer@biomed.ee.ethz.ch [Institute for Biomedical Engineering, ETH and University of Zurich, Gloriastrasse 35, CH-8092 Zurich (Switzerland); Wilm, Bertram J. [Institute for Biomedical Engineering, ETH and University of Zurich, Gloriastrasse 35, CH-8092 Zurich (Switzerland); Froehlich, Johannes M. [Guerbet AG, Scientific Affairs, Winterthurerstrasse 92, CH-8006 Zurich (Switzerland); Gutzeit, Andreas [Department of Radiology, Cantonal Hospital Winterthur, Brauerstrasse 15, CH-8401 Winterthur (Switzerland); Prikler, Ladislav; Gablinger, Roger [Uroviva, Specialist Hospital for Urology, Zuerichstrasse 5, CH-8180 Buelach (Switzerland); Boesiger, Peter [Institute for Biomedical Engineering, ETH and University of Zurich, Gloriastrasse 35, CH-8092 Zurich (Switzerland); Wentz, Klaus-Ulrich [Institute for Biomedical Engineering, ETH and University of Zurich, Gloriastrasse 35, CH-8092 Zurich (Switzerland); Department of Radiology, Cantonal Hospital Muensterlingen, CH-8596 Muensterlingen (Switzerland)

    2011-11-15

    Objective: Diffusion tensor imaging (DTI) offers the promise of improved tumor localization in prostate cancer but the technique suffers from susceptibility-induced artifacts that limit the achievable resolution. The present work employs a reduced field-of-view technique that enables high-resolution DTI of the prostate at 3 T. Feasibility of the approach is demonstrated in a clinical study including 26 patients and 14 controls. Materials and methods: Reduced field-of-view acquisition was established by non-coplanar application of the excitation and the refocusing pulse in conjunction with outer volume suppression. Accuracy for cancer detection of apparent diffusion coefficient (ADC) mapping and T{sub 2}-weighted imaging was calculated and compared with reference to the findings of trans-rectal ultrasound-guided octant biopsy. Mean ADCs and fractional anisotropy (FA) values in the patients with positive and negative biopsies were compared to each other and to the controls. Results: Fine anatomical details were successfully depicted on the ADC maps with sub-millimeter resolution. Accuracy for prostate cancer detection was 73.5% for ADC maps and 71% for T{sub 2}-weighted images, respectively. Cohen's kappa ({kappa} = 0.48) indicated moderate agreement of the two methods. The mean ADCs were significantly lower, the FA values higher, in the patients with positive biopsy than in the patients with negative biopsy and the controls. Monte Carlo simulations showed that the FA values, but not the ADCs, were slightly overestimated. Bootstrap analysis revealed that the ADC, but not the FA value, is a highly repeatable marker. Conclusion: In conclusion, the present work introduces a new approach for high-resolution DTI of the prostate enabling a more accurate detection of focal tumors especially useful in screening populations or as a potential navigator for image-guided biopsy.

  4. Reduced retinoids and retinoid receptors' expression in pancreatic cancer: A link to patient survival.

    Science.gov (United States)

    Bleul, Tim; Rühl, Ralph; Bulashevska, Svetlana; Karakhanova, Svetlana; Werner, Jens; Bazhin, Alexandr V

    2015-09-01

    Pancreatic ductal adenocarcinoma (PDAC) represents one of the deadliest cancers in the world. All-trans retinoic acid (ATRA) is the major physiologically active form of vitamin A, regulating expression of many genes. Disturbances of vitamin A metabolism are prevalent in some cancer cells. The main aim of this work was to investigate deeply the components of retinoid signaling in PDAC compared to in the normal pancreas and to prove the clinical importance of retinoid receptor expression. For the study, human tumor tissues obtained from PDAC patients and murine tumors from the orthotopic Panc02 model were used for the analysis of retinoids, using high performance liquid chromatography mass spectrometry and real-time RT-PCR gene expression analysis. Survival probabilities in univariate analysis were estimated using the Kaplan-Meier method and the Cox proportional hazards model was used for the multivariate analysis. In this work, we showed for the first time that the ATRA and all-trans retinol concentration is reduced in PDAC tissue compared to their normal counterparts. The expression of RARα and β as well as RXRα and β are down-regulated in PDAC tissue. This reduced expression of retinoid receptors correlates with the expression of some markers of differentiation and epithelial-to-mesenchymal transition as well as of cancer stem cell markers. Importantly, the expression of RARα and RXRβ is associated with better overall survival of PDAC patients. Thus, reduction of retinoids and their receptors is an important feature of PDAC and is associated with worse patient survival outcomes.

  5. High-resolution diffusion tensor imaging of prostate cancer using a reduced FOV technique

    International Nuclear Information System (INIS)

    Objective: Diffusion tensor imaging (DTI) offers the promise of improved tumor localization in prostate cancer but the technique suffers from susceptibility-induced artifacts that limit the achievable resolution. The present work employs a reduced field-of-view technique that enables high-resolution DTI of the prostate at 3 T. Feasibility of the approach is demonstrated in a clinical study including 26 patients and 14 controls. Materials and methods: Reduced field-of-view acquisition was established by non-coplanar application of the excitation and the refocusing pulse in conjunction with outer volume suppression. Accuracy for cancer detection of apparent diffusion coefficient (ADC) mapping and T2-weighted imaging was calculated and compared with reference to the findings of trans-rectal ultrasound-guided octant biopsy. Mean ADCs and fractional anisotropy (FA) values in the patients with positive and negative biopsies were compared to each other and to the controls. Results: Fine anatomical details were successfully depicted on the ADC maps with sub-millimeter resolution. Accuracy for prostate cancer detection was 73.5% for ADC maps and 71% for T2-weighted images, respectively. Cohen's kappa (κ = 0.48) indicated moderate agreement of the two methods. The mean ADCs were significantly lower, the FA values higher, in the patients with positive biopsy than in the patients with negative biopsy and the controls. Monte Carlo simulations showed that the FA values, but not the ADCs, were slightly overestimated. Bootstrap analysis revealed that the ADC, but not the FA value, is a highly repeatable marker. Conclusion: In conclusion, the present work introduces a new approach for high-resolution DTI of the prostate enabling a more accurate detection of focal tumors especially useful in screening populations or as a potential navigator for image-guided biopsy.

  6. The Malignant Phenotype of Breast Cancer Cells Is Reduced by COX-2 Silencing

    Directory of Open Access Journals (Sweden)

    Ioannis Stasinopoulos

    2008-11-01

    Full Text Available The cyclooxygenase (COX pathway is currently targeted for therapeutic intervention in different cancers. We have previously shown that silencing of COX-2 in the poorly differentiated metastatic breast cell line MDA-MB-231 by RNA interference markedly delayed tumor onset and inhibited metastasis. To understand the functional effects of COX-2 silencing underlying the inhibition of tumor growth and metastasis previously reported, we investigated changes in these cells for a number of cancer-associated phenotypes. Cyclooxygenase-2-silenced cells were less able to acidify tissue culture medium, a response that could partly be attributed to decreased lactate production or export detected by reduced lactate in the medium. Consistent with the significantly reduced transcript levels of hyaluronan synthase 2, an enzyme responsible for the total level of hyaluronan secreted by these cells, COX-2 silencing resulted in lower hyaluronan levels secreted in culture medium. Inhibition of human umbilical vein endothelial cell network association in a coculture assay was also observed in COX-2-silenced cells. These data highlight the functional role of COX-2 in pathways that mediate increased malignancy.

  7. Should We Offer Medication to Reduce Breast Cancer Risk?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

    Science.gov (United States)

    Burns, Risa B; Schonberg, Mara A; Tung, Nadine M; Libman, Howard

    2016-08-01

    In November 2013, the U.S. Preventive Services Task Force issued a guideline on medications for risk reduction of primary breast cancer in women. Although mammography can detect early cases, it cannot prevent development of breast cancer. Tamoxifen and raloxifene are selective estrogen receptor modulators that have been shown to reduce the risk for estrogen receptor-positive breast cancer and are approved by the U.S. Food and Drug Administration (FDA) for this indication. However, neither medication reduces the risk for estrogen receptor-negative breast cancer or all-cause mortality. The Task Force concluded that postmenopausal women with an estimated 5-year risk for breast cancer of 3% or greater will probably have more net benefit than harm and recommends that clinicians engage in shared, informed decision making about these medications. The American Society of Clinical Oncology issued a practice guideline on use of pharmacologic interventions for breast cancer in 2013. It recommends that women aged 35 years or older at increased risk, defined as a 5-year absolute risk for breast cancer of 1.66% or greater, discuss breast cancer prevention medications with their primary care practitioner. The Society includes the aromatase inhibitor exemestane in addition to tamoxifen and raloxifene as a breast cancer prevention medication, although exemestane is not FDA approved for this indication. Here, an oncologist and an internist discuss how they would balance these recommendations and what they would suggest for an individual patient. PMID:27479221

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

    Science.gov (United States)

    2015-12-09

    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

  9. 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)

    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

  10. 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.

  11. 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

  12. Risk-Reducing Salpingo-oophorectomy and Ovarian Cancer Screening in 1077 Women After BRCA Testing

    Science.gov (United States)

    Mannis, Gabriel N.; Fehniger, Julia E.; Creasman, Jennifer S.; Jacoby, Vanessa L.; Beattie, Mary S.

    2016-01-01

    Background For women at potentially increased risk for ovarian cancer, data regarding screening and risk reduction are limited. Previous studies have reported on the behaviors of BRCA mutation carriers, but less is known about the behaviors of non-BRCA carriers. We surveyed a large cohort of women after BRCA testing to identify the prevalence and posttest predictors of risk-reducing and screening interventions. Methods A median of 3.7 years after BRCA testing, 1447 women who received genetic counseling and BRCA testing at 2 hospital sites were surveyed, with a 77.6% response rate. We analyzed data from 1077 survey respondents. We performed univariate and multivariate logistic regression analyses to identify predictors of risk-reducing salpingo-oophorectomy (RRSO), screening transvaginal ultrasonography (TVUS), and screening serum cancer antigen 125 (CA-125). Results Among the respondents, 201 women (18.7%) received positive test results for a deleterious mutation, 103 women (9.6%) received true-negative results, and 773 women (71.8%) received uninformative results. Overall, 19.1% of eligible women underwent RRSO and 39.6% used screening procedures. A positive BRCA result predicted RRSO (odds ratio [OR], 28.1; 95% CI, 16.2-48.6), TVUS (9.5 [4.3-21.0]), and serum CA-125 (13.0 [5.5-29.0]). Similarly, a true-negative BRCA result reduced the OR for RRSO (0.1 [0.0-0.6]), TVUS (0.2 [0.1-0.5]), and serum CA-125 (0.3 [0.1-0.7]). Of the 71.8% of women who received uninformative results after BRCA testing, 12.3% subsequently underwent RRSO, 33.8% reported ever having undergone screening serum CA-125 since BRCA testing, and 37.3% reported ever having undergone screening TVUS since BRCA testing. Conclusions Results of BRCA testing strongly predict RRSO and ovarian cancer screening. Use of RRSO and ovarian screening was reported in a sizable percentage of non-BRCA carriers despite insufficient data to determine the effectiveness of these interventions. PMID:23247828

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

    International Nuclear Information System (INIS)

    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

  14. A polymeric colchicinoid prodrug with reduced toxicity and improved efficacy for vascular disruption in cancer therapy

    Directory of Open Access Journals (Sweden)

    Crielaard BJ

    2011-11-01

    Full Text Available Bart J Crielaard1, Steffen van der Wal1, Twan Lammers2, Huong Thu Le1, Wim E Hennink1, Raymond M Schiffelers1, Gert Storm1, Marcel HAM Fens11Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; 2Department of Experimental Molecular Imaging, RWTH Aachen University, Aachen, Germany The first two authors contributed equally to this work. Abstract: Colchicinoids are very potent tubulin-binding compounds, which interfere with microtubule formation, giving them strong cytotoxic properties, such as cell mitosis inhibition and induction of microcytoskeleton depolymerization. While this makes them promising vascular disrupting agents (VDAs in cancer therapy, their dose-limiting toxicity has prevented any clinical application for this purpose. Therefore, colchicinoids are considered attractive lead molecules for the development of novel vascular disrupting nanomedicine. In a previous study, a polymeric colchicinoid prodrug that showed favorable hydrolysis characteristics at physiological conditions was developed. In the current study, this polymeric colchicinoid prodrug was evaluated in vitro and in vivo for its toxicity and vascular disrupting potential. Cell viability studies with human umbilical vein endothelial cells, as an in vitro measure for colchicine activity, reflected the degradation kinetics of the prodrug accordingly. Upon intravenous treatment, in vivo, of B16F10 melanoma-bearing mice with colchicine or with the polymeric colchicinoid prodrug, apparent vascular disruption and consequent tumor necrosis was observed for the prodrug but not for free colchicine at an equivalent dose. Moreover, a five-times-higher dose of the prodrug was well tolerated, indicating reduced toxicity. These findings demonstrate that the polymeric colchicinoid prodrug has a substantially improved efficacy/toxicity ratio compared with that of colchicine, making it a promising VDA for cancer therapy

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

    NARCIS (Netherlands)

    I. van der Waal

    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 ca

  16. Meta-analysis of studies using statins as a reducer for primary liver cancer risk

    Science.gov (United States)

    Zhong, Guo-Chao; Liu, Yan; Ye, Yuan-Yuan; Hao, Fa-Bao; Wang, Kang; Gong, Jian-Ping

    2016-01-01

    A protective effect of statins on primary liver cancer (PLC) risk has been suggested. However, issues about the dose–response relationship, the protective effect of individual statins, and PLC risk reduction among at-risk populations remain unsolved. Therefore, a meta-analysis was conducted. PubMed and EMBASE were searched for studies providing the risk ratio (RR) on statins and PLC risk. Summary RRs were calculated using a random-effects model. Twenty-five studies were identified. Stain use was significantly associated with a reduced risk of PLC (RR = 0.60, 95% confidence interval (CI) = 0.53–0.69). The summary RR for every additional 50 cumulative defined daily doses per year was 0.87 (95% CI = 0.83–0.91). Evidence of a non-linear dose–response relationship between statins and PLC risk was found (Pnon-linearity < 0.01). All individual statins significantly reduced PLC risk, and the risk reduction was more evident with rosuvastatin. The inverse association between statins and PLC risk remained among populations with common risk factors. Subgroup analyses revealed more significant reduction in PLC risk by statins in high- versus non-high-risk populations (Pinteraction = 0.02). Overall, these findings add to our understanding of the association between statins and PLC risk. Whether statin use is causally associated with a reduced risk of PLC should be further studied. PMID:27198922

  17. Sorafenib treatment during partial hepatectomy reduces tumorgenesis in an inflammation-associated liver cancer model

    Science.gov (United States)

    Salmon, Asher; Peretz, Tamar; Galun, Eithan; Axelrod, Jonathan H.; Sonnenblick, Amir

    2016-01-01

    The long-term prognosis after resection of hepatocellular carcinoma (HCC), which is one of the treatment options for early-stage HCC, remains unsatisfactory as a result of a high incidence of disease recurrence. Recent studies performed in murine models revealed a link between liver regeneration under chronic inflammation and hepatic tumorigenesis. Sorafenib is a potent drug for advanced HCC with multikinase inhibition activity. We propose that inhibition of signal transduction pathways which are activated during hepatectomy, using Sorafenib, will reduce accelerated tumorigenesis. To test this hypothesis, we studied the Mdr2-knockout (KO) mouse strain, a model of inflammation-associated cancer, which underwent partial hepatectomy (PHx) at three months of age, with or without Sorafenib. Here we show that Sorafenib treatment during PHx inhibited different signal transduction pathways at the multikinase levels, but did not result in increased morbidity or mortality. At the early stages after PHx, Sorafenib treatment had no effect on the course of proliferation, apoptosis and DNA repair in the regenerating liver, but resulted in decreased stellate cells activation and inflammatory response. Finally, we show that Sorafenib treatment during PHx at three months of age resulted in decreased fibrosis and tumor formation at 8.5 months. In conclusion our study indicates that short-term Sorafenib treatment during PHx is safe and effective in inhibiting inflammation-associated cancer, and is therefore a potential strategy for recurrence prevention in patients with early-stage HCC treated with PHx. PMID:26695439

  18. relA over-expression reduces tumorigenicity and activates apoptosis in human cancer cells

    Science.gov (United States)

    Ricca, A; Biroccio, A; Trisciuoglio, D; Cippitelli, M; Zupi, G; Bufalo, D Del

    2001-01-01

    We previously demonstrated that bcl-2 over-expression increases the malignant behaviour of the MCF7 ADR human breast cancer cell line and enhances nuclear factor-kappa B (NF-k B) transcriptional activity. Here, we investigated the direct effect of increased NF-k B activity on the tumorigenicity of MCF7 ADR cells by over-expressing the NF-k B subunit relA/p65. Surprisingly, our results demonstrated that over-expression of relA determines a considerable reduction of the tumorigenic ability in nude mice as indicated by the tumour take and the median time of tumour appearance. In vitro studies also evidenced a reduced cell proliferation and the activation of the apoptotic programme after relA over-expression. Apoptosis was associated with the production of reactive oxygen species, and the cleavage of the specific substrate Poly-ADP-ribose-polymerrase. Our data indicate that there is no general role for NF-k B in the regulation of apoptosis and tumorigenicity. In fact, even though inhibiting NF-k B activity has been reported to be lethal to tumour cells, our findings clearly suggest that an over-induction of nuclear NF-k B activity may produce the same effect. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11747334

  19. 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...... of tumor subtypes in ALN involvement. The risk of ALN metastases at the time of diagnosis was significantly reduced in HR-negative patients compared to HR-positive patients [adjusted odds ratio (OR) 0.69; 95 % CI 0.63-0.76; P = 0.0009]. A HER2-positive status was associated with an increased risk of ALN...... involvement at diagnosis compared to a HER2-negative status (OR 1.37; 95 % CI 1.24-1.50; P positive status significantly associated with ALN involvement at the time of diagnosis only in HR-negative patients (P

  20. 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.

  1. Potential opportunities to reduce cervical cancer by addressing risk factors other than HPV

    OpenAIRE

    Kumar, Ramaiah Vinay; Bhasker, Suman

    2013-01-01

    Cervical cancer is the most common cancer in developing world and 80% of global burden is reported from these nations. Human papillomavirus along with poverty, illiteracy/lower education level and standards, multi-parity, tobacco, malnutrition and poor genital hygiene may act synergistically to cause cervical cancer. Risk factor of cervical cancer may in itself be the reason for non-viability of cervical cancer vaccine program in this part of the world. Interventions to address these risk fac...

  2. Antithrombin reduces reperfusion-induced hepatic metastasis of colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Masanao Kurata; Kenji Okajima; Toru Kawamoto; Mitsuhiro Uchiba; Nobuhiro Ohkohchi

    2006-01-01

    AIM: To examine whether antithrombin (AT) could prevent hepatic ischemia/reperfusion (I/R)-induced hepatic metastasis by inhibiting tumor necrosis factor (TNF)-α-induced expression of E-selectin in rats.METHODS: Hepatic I/R was induced in rats and mice by clamping the left branches of the portal vein and the hepatic artery. Cancer cells were injected intrasplenically.The number of metastatic nodules was counted on day 7after I/R. TNF-α and E-selectin mRNA in hepatic tissue,serum fibrinogen degradation products and hepatic tissue levels of 6-keto-PGF1α, a stable metabolite of PGI2,were measured.RESULTS: AT inhibited increases in hepatic metastasis of tumor cells and hepatic tissue mRNA levels of TNF-αand E-selectin in animals subjected to hepatic I/R.Argatroban, a thrombin inhibitor, did not suppress any of these changes. Both AT and argatroban inhibited I/R-induced coagulation abnormalities. I/R-induced increases of hepatic tissue levels of 6-keto-PGF1αwere significantly enhanced by AT. Pretreatment with indomethacin completely reversed the effects of AT.Administration of OP-2507, a stable PGI2 analog, showed effects similar to those of AT in this model. Hepatic metastasis in congenit.al AT-deficient mice subjected to hepatic I/R was significantly increased compared to that observed in wild-type mice. Administration of AT significantly reduced the number of hepatic metastases in congenital AT-deficient mice.CONCLUSION: AT might reduce I/R-induced hepatic metastasis of colon cancer cells by inhibiting TNF-α-induced expression of E-selectin through an increase in the endothelial production of PGI2. These findings also raise the possibility that AT might prevent hepatic metastasis of tumor cells if administered during the resection of liver tumors.

  3. 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.

  4. ERK/p38 MAPK inhibition reduces radio-resistance to a pulsed proton beam in breast cancer stem cells

    Science.gov (United States)

    Jung, Myung-Hwan; Park, Jeong Chan

    2015-10-01

    Recent studies have identified highly tumorigenic cells with stem cell-like characteristics, termed cancer stem cells (CSCs) in human cancers. CSCs are resistant to conventional radiotherapy and chemotherapy owing to their high DNA repair ability and oncogene overexpression. However, the mechanisms regulating CSC radio-resistance, particularly proton beam resistance, remain unclear. We isolated CSCs from the breast cancer cell lines MCF-7 and MDA-MB-231, which expressed the characteristic breast CSC membrane protein markers CD44+/CD24-/ low , and irradiated the CSCs with pulsed proton beams. We confirmed that CSCs were resistant to pulsed proton beams and showed that treatment with p38 and ERK inhibitors reduced CSC radio-resistance. Based on these results, BCSC radio-resistance can be reduced during proton beam therapy by co-treatment with ERK1/2 or p38 inhibitors, a novel approach to breast cancer therapy.

  5. 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.

  6. Müllerian intra-abdominal carcinomatosis in hereditary breast ovarian cancer syndrome: implications for risk-reducing surgery.

    Science.gov (United States)

    Casey, Murray Joseph; Colanta, Agnes B

    2016-07-01

    More than 40 years ago Lynch et al. described several multigenerational breast cancer family pedigrees which demonstrated autosomal dominant inheritance of a trait(s) that increased risks for both breast and ovarian cancers. Mutation carriers in at least 90 % of these hereditary breast ovarian cancer (HBOC) syndrome families have been linked to cancer-associated mutations in the genes BRCA1 and BRCA2. This review focuses on the contributions of Lynch, colleagues and collaborators and pertinent literature, toward defining the HBOC syndrome, the cancer risks that the inherited adverse mutations convey, the gynecologic tissues and organs from which the malignancy may arise to disseminate throughout the pelvic and abdominal organs and peritoneum and how this information can be used to reduce the risk and morbidities of intra-abdominal carcinomatosis in effected individuals. PMID:26875157

  7. Association of NDRG1 gene promoter methylation with reduced NDRG1 expression in gastric cancer cells and tissue specimens.

    Science.gov (United States)

    Chang, Xiaojing; Zhang, Shuanglong; Ma, Jinguo; Li, Zhenhua; Zhi, Yu; Chen, Jing; Lu, Yao; Dai, Dongqiu

    2013-05-01

    NDRG1 (N-myc downstream-regulated gene 1) plays a role in cell differentiation and suppression of tumor metastasis. This study aims to determine the expression of NDRG1 mRNA and protein in gastric cancer cell lines and tissue specimens and then assess the possible cause of its aberrant expression. Six gastric cancer cell lines and 20 pairs of normal and gastric cancer tissue samples were used to assess NDRG1 expression using Real-time PCR and Western blot. High-resolution melting analysis (HRM) and methylation-specific PCR (MSP) were performed to detect gene mutation and methylation, respectively, in cell lines and tissues samples. Expression of NDRG1 mRNA and protein was downregulated in gastric cancer cell lines and tissues. Specifically, expression of NDRG1 mRNA and protein was lower in all six gastric cancer cell lines than that of normal gastric cells, while 15 out of 20 cases of gastric cancer tissues had the reduced levels of NDRG1 mRNA and protein. HRM data showed that there was no mutation in NDRG1 gene, but MSP data showed high levels of NDRG1 gene promoter methylation in the CpG islands in both cell lines and tissue samples. Moreover, treatment with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine upregulated NDRG1 expression in gastric cancer HGC27 cells, but not in the histone deacetylase inhibitor trichostatin A-treated HGC27 cells. In conclusion, this study has shown that expression of NDRG1 mRNA and protein was reduced in gastric cancer cell lines and tissues, which is due to methylation of NDRG1 gene promoter. Further study will unearth the clinical significance of the reduced NDRG1 protein in gastric cancer.

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

    OpenAIRE

    Ting-Hao Chen; Tao-Hsin Tung; Pei-Shih Chen; Shu-Hui Wang; Chuang-Min Chao; Nan-Hsing Hsiung; Ching-Chi Chi

    2016-01-01

    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, cance...

  9. Transcriptome 2002 Conference

    Energy Technology Data Exchange (ETDEWEB)

    Quackenbush, John

    2002-01-01

    The Transcriptome 2002 meeting was held March 11-13, 2002 in Seattle, Washington with attendance by more than 300 scientists representing the international community. The scientific program was developed by an international organizing committee. In association with the main meeting, an Image Consortium invitational meeting was organized by Charles Auffray of CNRS and held with approximately 40 participants immediately following the conclusion of the Transcriptome meeting.

  10. Abrogation of junctional adhesion molecule-A expression induces cell apoptosis and reduces breast cancer progression.

    Directory of Open Access Journals (Sweden)

    Masato Murakami

    Full Text Available Intercellular junctions promote homotypic cell to cell adhesion and transfer intracellular signals which control cell growth and apoptosis. Junctional adhesion molecule-A (JAM-A is a transmembrane immunoglobulin located at tight junctions of normal epithelial cells of mammary ducts and glands. In the present paper we show that JAM-A acts as a survival factor for mammary carcinoma cells. JAM-A null mice expressing Polyoma Middle T under MMTV promoter develop significantly smaller mammary tumors than JAM-A positive mice. Angiogenesis and inflammatory or immune infiltrate were not statistically modified in absence of JAM-A but tumor cell apoptosis was significantly increased. Tumor cells isolated from JAM-A null mice or 4T1 cells incubated with JAM-A blocking antibodies showed reduced growth and increased apoptosis which paralleled altered junctional architecture and adhesive function. In a breast cancer clinical data set, tissue microarray data show that JAM-A expression correlates with poor prognosis. Gene expression analysis of mouse tumor samples showed a correlation between genes enriched in human G3 tumors and genes over expressed in JAM-A +/+ mammary tumors. Conversely, genes enriched in G1 human tumors correlate with genes overexpressed in JAM-A-/- tumors. We conclude that down regulation of JAM-A reduces tumor aggressive behavior by increasing cell susceptibility to apoptosis. JAM-A may be considered a negative prognostic factor and a potential therapeutic target.

  11. Targeting Id1 reduces proliferation and invasion in aggressive human salivary gland cancer cells

    International Nuclear Information System (INIS)

    Salivary gland cancer (SGC) is one of the common malignancies of the head and neck area. It develops in the minor and major salivary glands and sometimes metastasizes to other organs, particularly to the lungs. Inhibitors of differentiation (Id) proteins are negative regulators of basic helix-loop-helix transcription factors that control malignant cell behavior and tumor aggressiveness in many tissues. In this study, our goal was to determine the potential role of Id proteins, particularly Id1, during human SGC cell progression. We first determined the expression levels of Id1 and Id2 in four SGC cell lines: two adenocarcinoma of the salivary gland (HSG and HSY) and two adenoid cystic carcinoma (ACC2 and ACCM) cell lines. We then used constructs that expressed antisense cDNAs to Id1 or Id2 to knockdown the expression of these proteins in cell lines where they were highly expressed, and determined the effects of the knockdown on cell proliferation, migration and invasion. Id1 mRNA and protein were detectable in all cell lines, and expression of Id2 was variable, from absent to high. The ACC2 and ACCM cell lines expressed both Id1 and Id2, but Id1 was expressed at a higher level in the more aggressive ACCM cell line in comparison toACC2 cells as confirmed by Id1 promoter-reporter assays. We therefore focused on the ACCM cells for the remainder of the study. We found that proliferation and invasiveness of ACCM cells were strongly reduced after Id1 knockdown whereas Id2 suppression had only a slight effect. Results of scratch and colony formation assays also confirmed that ACCM cell aggressiveness was significantly reduced upon Id1 knockdown. Finally, this knockdown resulted in reduced c-myc and enhanced cyclin-dependent kinase inhibitor p21 expression. These results demonstrate that Id1 plays an important role in the control of human SGC cell aggressiveness and suggest a potential role as a marker of diagnosis, prognosis and progression of SGCs. Id1 suppression could

  12. 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.

  13. Ovarian Cancer Screening Method Fails to Reduce Deaths from the Disease

    Science.gov (United States)

    New results from the NCI-sponsored PLCO Cancer Screening Trial show that screening for ovarian cancer with transvaginal ultrasound (TVU) and the CA-125 blood test did not result in fewer deaths from the disease compared with usual care.

  14. Relaxin reduces xenograft tumour growth of human MDA-MB-231 breast cancer cells

    OpenAIRE

    Radestock, Yvonne; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine

    2008-01-01

    Introduction Relaxin levels are increased in cases of human breast cancer and has been shown to promote cancer cell migration in carcinoma cells of the breast, prostate gland and thyroid gland. In oestrogen receptor alpha-negative MDA-MB-231 human breast cancer cells, relaxin was shown to down-regulate the metastasis-promoting protein S100A4 (metastasin), a highly significant prognostic factor for poor survival in breast cancer patients. The cellular mechanisms of relaxin exposure in breast c...

  15. 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

    Directory of Open Access Journals (Sweden)

    Xia Rui

    2011-10-01

    Full Text Available Abstract Background 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. Results 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. Conclusions This study provides an extensive transcriptome study and a good platform for further investigation of possible

  16. Preoperative dexamethasone reduces postoperative pain, nausea and vomiting following mastectomy for breast cancer

    International Nuclear Information System (INIS)

    Dexamethasone has been reported to reduce postoperative symptoms after different surgical procedures. We evaluated the efficacy of preoperative dexamethasone in ameliorating postoperative nausea and vomiting (PONV), and pain after mastectomy. In this prospective, double-blind, placebo-controlled study, 70 patients scheduled for mastectomy with axillary lymph node dissection were analyzed after randomization to treatment with 8 mg intravenous dexamethasone (n = 35) or placebo (n = 35). All patients underwent standardized procedures for general anesthesia and surgery. Episodes of PONV and pain score were recorded on a visual analogue scale. Analgesic and antiemetic requirements were also recorded. Demographic and medical variables were similar between groups. The incidence of PONV was lower in the dexamethasone group at the early postoperative evaluation (28.6% vs. 60%; p = 0.02) and at 6 h (17.2% vs. 45.8%; p = 0.03). More patients in the placebo group required additional antiemetic medication (21 vs. 8; p = 0.01). Dexamethasone treatment significantly reduced postoperative pain just after surgery (VAS score, 4.54 ± 1.55 vs. 5.83 ± 2.00; p = 0.004), at 6 h (3.03 ± 1.20 vs. 4.17 ± 1.24; p < 0.0005) and at 12 h (2.09 ± 0.85 vs. 2.54 ± 0.98; p = 0.04). Analgesics were required in more patients of the control group (21 vs. 10; p = 0.008). There were no adverse events, morbidity or mortality. Preoperative intravenous dexamethasone (8 mg) can significantly reduce the incidence of PONV and pain in patients undergoing mastectomy with axillary dissection for breast cancer. NCT01116713

  17. An association between anti-platelet drug use and reduced cancer prevalence in diabetic patients: results from the Vermont Diabetes Information System Study

    OpenAIRE

    Ramos-Nino Maria E; Holmes Chris E; Littenberg Benjamin

    2010-01-01

    Abstract Background Diabetes is associated with an increased risk of several malignancies. Both diabetic patients and patients with cancer have an increase in platelet reactivity and platelet activation has recently emerged as a potential mediator of cancer progression. Drug therapies, such as aspirin, that reduce platelet reactivity reduce both cardiovascular and cancer risk. Methods We performed a cross-sectional analysis to assess the association between history of cancer and current anti-...

  18. Deep inspiration breath hold technique reduces heart dose from radiotherapy for left-sided breast cancer

    International Nuclear Information System (INIS)

    Adjuvant left breast radiotherapy (ALBR) for breast cancer can result in significant radiation dose to the heart. Current evidence suggests a dose–response relationship between the risk of cardiac morbidity and radiation dose to cardiac volumes. This study explores the potential benefit of utilising a deep inspiration breath hold (DIBH) technique to reduce cardiac doses. Thirty patients with left-sided breast cancer underwent CT-simulation scans in free breathing (FB) and DIBH. Treatment plans were generated using a hybrid intensity-modulated radiation therapy technique with simultaneous integrated boost. A dosimetric comparison was made between the two techniques for the heart, left anterior descending coronary artery (LAD), left lung and contralateral breast. Compared with FB, DIBH resulted in a significant reduction in heart V30 (7.1 vs. 2.4%, P < 0.0001), mean heart dose (6.9 vs. 3.9 Gy, P < 0.001), maximum LAD planning risk volume (PRV) dose, (51.6 vs. 45.6 Gy, P = 0.0032) and the mean LAD PRV dose (31.7 vs. 21.9 Gy, P < 0.001). No significant difference was noted for lung V20, mean lung dose or mean dose to the contralateral breast. The DIBH plans demonstrated significantly larger total lung volumes (1126 vs. 2051 cc, P < 0.0001), smaller maximum heart depth (2.08 vs. 1.17 cm, P < 0.0001) and irradiated heart volume (36.9 vs. 12.1 cc, P < 0.0001). DIBH resulted in a significant reduction in radiation dose to the heart and LAD compared with an FB technique for ALBR. Ongoing research is required to determine optimal cardiac dose constraints and methods of predicting which patients will derive the most benefit from a DIBH technique.

  19. [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

    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...... to indicate that problems in the areas of sufficient capacity for diagnostic workup and treatment may explain some of the difference in survival between Danish and Swedish cancer patients Udgivelsesdato: 2001/1/22...

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

    Science.gov (United States)

    2016-03-07

    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

  1. Randomized Trial of a Pre-Surgical Scheduled Reduced Smoking Intervention for Patients Newly Diagnosed with Cancer

    Science.gov (United States)

    Ostroff, Jamie S.; Burkhalter, Jack E.; Cinciripini, Paul M.; Li, Yuelin; Shiyko, Mariya P.; Lam, Cho Y.; Hay, Jennifer L.; Dhingra, Lara K.; Lord-Bessen, Jennifer; Holland, Susan M.; Manna, Ruth

    2014-01-01

    Objective Cancer patients are advised to quit smoking to reduce treatment complications and future cancer risk. This study's main objective was to evaluate the efficacy of a novel, pre-surgical cessation intervention in newly diagnosed cancer patients scheduled for surgical hospitalization. Methods We conducted a parallel-arm, randomized controlled trial comparing the efficacy of our hospital-based, tobacco cessation “best practices” treatment model (BP; cessation counseling and nicotine replacement therapy) with BP enhanced by a behavioral tapering regimen (scheduled reduced smoking; BP+SRS) administered by a handheld computer before hospitalization for surgery. Cessation outcomes were short (hospital admission and three months) and longer-term (6 months) biochemically-verified smoking abstinence. We hypothesized that BP+SRS would be superior to BP alone. One hundred eighty-five smokers were enrolled. Results Overall, 7-day-point prevalence, confirmed abstinence rates at six months for BP alone (32%) and BP+SRS (32%) were high; however, no main effect of treatment was observed. Patients who were older and diagnosed with lung cancer were more likely to quit smoking. Conclusions Compared to best practices for treating tobacco dependence, a pre-surgical, scheduled reduced smoking intervention did not improve abstinence rates among newly diagnosed cancer patients. PMID:23895203

  2. Transcriptional silencing of ETS-1 abrogates epithelial-mesenchymal transition resulting in reduced motility of pancreatic cancer cells.

    Science.gov (United States)

    Li, Chunyan; Wang, Zhonghan; Chen, Yan; Zhou, Min; Zhang, Haijun; Chen, Rong; Shi, Fangfang; Wang, Cailian; Rui, Zongdao

    2015-02-01

    v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS-1) plays crucial roles in a spectrum of malignancies. ETS-1 has gained attention in cancer research for its importance in cell migration, invasion and proliferation. In the present study, we focused on the effect of ETS-1 on epithelial-mesenchymal transition (EMT), which is characterized by reduced E-cadherin expression and increased N-cadherin expression. We found that ETS-1 mRNA expression was positively correlated with N-cadherin and negatively correlated with E-cadherin mRNA expression in five pancreatic cancer cell lines. To elucidate the functionality of ETS-1 on EMT in pancreatic cancer cells, we constructed a green fluorescent protein (GFP)-expressing plasmid carrying ETS-1 short hairpin RNA (shRNA), and transfected Panc-1 cells with the plasmid. We detected reduced N-cadherin and vascular endothelial growth factor yet higher E-cadherin expression in the ETS-1-silenced cells compared with the control group. In addition, we observed reduced cell migration and increased adhesion in these cells. Our data showed that ETS-1 actively functioned as a regulator of EMT in Panc-1 cells, and provide additional evidence supporting a fundamental role for ETS-1 in metastatic pancreatic cancer cells. These results suggest that analysis of ETS-1 expression levels may provide an avenue for evaluating prognosis in pancreatic cancer.

  3. Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain.

    Science.gov (United States)

    Pan, Ruirui; Di, Huiting; Zhang, Jinming; Huang, Zhangxiang; Sun, Yuming; Yu, Weifeng; Wu, Feixiang

    2015-01-01

    Although bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4) plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the downregulation of TLR4 by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for bone cancer pain, an inducible lentivirus LvOn-siTLR4 (tetracycline inducible lentivirus carrying siRNA targeting TLR4) was prepared and the antinociception effects were observed in bone cancer pain rats induced by Walker 256 cells injection in left leg. Results showed that LvOn-siTLR4 intrathecal injection with doxycycline (Dox) oral administration effectively reduced the nociception induced by Walker 256 cells while inhibiting the mRNA and protein expression of TLR4. Proinflammatory cytokines as TNF-α and IL-1β in spinal cord were also decreased. These findings suggest that TLR4 could be a target for bone cancer pain treatment and tetracycline inducible lentivirus LvOn-siTLR4 represents a new potential option for long-term treatment of bone cancer pain. PMID:26556957

  4. Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain

    Directory of Open Access Journals (Sweden)

    Ruirui Pan

    2015-01-01

    Full Text Available Although bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4 plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the downregulation of TLR4 by RNA interference; however, naked siRNA (small interference RNA is not effective in long-term treatments. In order to concoct a viable prolonged treatment for bone cancer pain, an inducible lentivirus LvOn-siTLR4 (tetracycline inducible lentivirus carrying siRNA targeting TLR4 was prepared and the antinociception effects were observed in bone cancer pain rats induced by Walker 256 cells injection in left leg. Results showed that LvOn-siTLR4 intrathecal injection with doxycycline (Dox oral administration effectively reduced the nociception induced by Walker 256 cells while inhibiting the mRNA and protein expression of TLR4. Proinflammatory cytokines as TNF-α and IL-1β in spinal cord were also decreased. These findings suggest that TLR4 could be a target for bone cancer pain treatment and tetracycline inducible lentivirus LvOn-siTLR4 represents a new potential option for long-term treatment of bone cancer pain.

  5. Suppression of Poly(rC)-Binding Protein 4 (PCBP4) reduced cisplatin resistance in human maxillary cancer cells.

    Science.gov (United States)

    Ito, Yumi; Narita, Norihiko; Nomi, Nozomi; Sugimoto, Chizuru; Takabayashi, Tetsuji; Yamada, Takechiyo; Karaya, Kazuhiro; Matsumoto, Hideki; Fujieda, Shigeharu

    2015-07-21

    Cisplatin plays an important role in the therapy for human head and neck cancers. However, cancer cells develop cisplatin resistance, leading to difficulty in treatment and poor prognosis. To analyze cisplatin-resistant mechanisms, a cisplatin-resistant cell line, IMC-3CR, was established from the IMC-3 human maxillary cancer cell line. Flow cytometry revealed that, compared with IMC-3 cells, cisplatin more dominantly induced cell cycle G2/M arrest rather than apoptosis in IMC-3CR cells. That fact suggests that IMC-3CR cells avoid cisplatin-induced apoptosis through induction of G2/M arrest, which allows cancer cells to repair damaged DNA and survive. In the present study, we specifically examined Poly(rC)-Binding Protein 4 (PCBP4), which reportedly induces G2/M arrest. Results showed that suppression of PCBP4 by RNAi reduced cisplatin-induced G2/M arrest and enhanced apoptosis in IMC-3CR cells, resulting in the reduction of cisplatin resistance. In contrast, overexpression of PCBP4 in IMC-3 cells induced G2/M arrest after cisplatin treatment and enhanced cisplatin resistance. We revealed that PCBP4 combined with Cdc25A and suppressed the expression of Cdc25A, resulting in G2/M arrest. PCBP4 plays important roles in the induction of cisplatin resistance in human maxillary cancers. PCBP4 is a novel molecular target for the therapy of head and neck cancers, especially cisplatin-resistant cancers.

  6. Can Avoiding Light at Night Reduce the Risk of Breast Cancer?

    Science.gov (United States)

    Keshet-Sitton, Atalya; Or-Chen, Keren; Yitzhak, Sara; Tzabary, Ilana; Haim, Abraham

    2016-06-01

    Excessive exposure to artificial light at night (ALAN) suppresses nocturnal melatonin (MLT) production in the pineal gland and is, therefore, associated with an increased risk of breast cancer (BC). We examined indoor and outdoor light habits of 278 women, BC patients (n = 93), and controls (n = 185; 2010-2014). Cases and controls were age and residential area matched. Data regarding behavior in the sleeping habitat in a 5-year period, 10 to 15 years prior to disease diagnosis, were collected using a questionnaire. Sleep quality, bedtime, sleep duration, TV watching habits, presleeping reading habits, subjective illumination intensity, and type of illumination were collected. Binary logistic regression models were used to calculate odds ratios with 95% confidence intervals (ORs with 95% CIs) for BC patients in relation to those habits. OR results revealed that women who had slept longer (controls), 10 to 15 years before the time of the study, in a period of 5 years, had a significant (OR = 0.74; 95% CI = 0.57-0.97; P < .03) reduced BC risk. Likewise, women who had been moderately exposed to ALAN as a result of reading using bed light (reading lamp) illumination and women who had slept with closed shutters reduced their BC risk: OR = 0.81, 95% CI = 0.67-0.97, P < .02, and OR = 0.82, 95% CI = 0.68-0.99, P < .04, respectively. However, women who had been exposed to ALAN as a result of living near strong illumination sources were at a significantly higher BC risk (OR = 1.52; 95% CI = 1.10-2.12; P < .01). These data support the hypothesis that diminishing nighttime light exposure will diminish BC risk and incidence. This hypothesis needs to be tested directly using available testing strategies and technologies that continuously measure an individual's light exposure, its timing, and sleep length longitudinally and feed this information back to the individual, so that BC risk can be distinguished prospectively. PMID:26631258

  7. High mobility group A1 protein expression reduces the sensitivity of colon and thyroid cancer cells to antineoplastic drugs

    OpenAIRE

    D’Angelo, Daniela; Mussnich, Paula; De Rosa, Roberta; Bianco, Roberto; Tortora, Giampaolo; Fusco, Alfredo

    2014-01-01

    Background Development of resistance to conventional drugs and novel biological agents often impair long-term chemotherapy. HMGA gene overexpression is often associated with antineoplastic drug resistance and reduced survival. Inhibition of HMGA expression in thyroid cancer cells reduces levels of ATM protein, the main cellular sensor of DNA damage, and enhances cellular sensitivity to DNA-damaging agents. HMGA1 overexpression promotes chemoresistance to gemcitabine in pancreatic adenocarcino...

  8. A New Approach to Reduce Toxicities and to Improve Bioavailabilities of Platinum-Containing Anti-Cancer Nanodrugs

    OpenAIRE

    Liu, Li; Ye, Qing; Lu, Maggie; Lo, Ya-Chin; Hsu, Yuan-Hung; Wei, Ming-Cheng; Chen, Yu-Hsiang; Lo, Shen-Chuan; Wang, Shian-Jy; Bain, Daniel J.; Ho, Chien

    2015-01-01

    Platinum (Pt) drugs are the most potent and commonly used anti-cancer chemotherapeutics. Nanoformulation of Pt drugs has the potential to improve the delivery to tumors and reduce toxic side effects. A major challenge for translating nanodrugs to clinical settings is their rapid clearance by the reticuloendothelial system (RES), hence increasing toxicities on off-target organs and reducing efficacy. We are reporting that an FDA approved parenteral nutrition source, Intralipid 20%, can help th...

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

    Science.gov (United States)

    Wei, Yao; Li, Mingzhen; Cui, Shufang; Wang, Dong; Zhang, Chen-Yu; Zen, Ke; Li, Limin

    2016-01-01

    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. PMID:27322220

  10. 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.

  11. REDUCED TOPOISOMERASE-II ACTIVITY IN MULTIDRUG-RESISTANT HUMAN NONSMALL CELL LUNG-CANCER CELL-LINES

    NARCIS (Netherlands)

    EIJDEMS, EWHM; DEHAAS, M; TIMMERMAN, AJ; VANDERSCHANS, GP; KAMST, E; DENOOIJ, J; RICOTTI, GCBA; BORST, P; BAAS, F

    1995-01-01

    Multidrug-resistant (MDR) cell lines often have a compound phenotype, combining reduced drug accumulation with a decrease in topoisomerase II. We have analysed alterations in topoisomerase II in MDR derivatives of the human lung cancer cell line SW-1573. Selection with doxorubicin frequently resulte

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

    NARCIS (Netherlands)

    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

    2016-01-01

    OBJECTIVES: 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 de

  13. Surveillance Recommendations in Reducing Risk of and Optimally Managing Breast Cancer-Related Lymphedema

    OpenAIRE

    Ostby, Pamela L.; Jane M Armer; Dale, Paul S.; Margaret J. Van Loo; Cassie L. Wilbanks; Stewart, Bob R.

    2014-01-01

    Breast cancer survivors are at increased risk for the development of breast cancer-related lymphedema (BCRL), a chronic, debilitating, and disfiguring condition that is progressive and requires lifelong self-management of symptoms. It has been reported that over 40% of the 2.5 million breast cancer survivors in the United States may meet the criteria for BCRL during their lifetimes. Ongoing surveillance, beginning with pre-operative assessment, has been effective in identifying subclinical ly...

  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. 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

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

    Science.gov (United States)

    Mladenova, Dessislava N; Dahlstrom, Jane E; Tran, Phuong N; Benthani, Fahad; Bean, Elaine G; Ng, Irvin; Pangon, Laurent; Currey, Nicola; Kohonen-Corish, Maija R J

    2015-09-01

    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 (Hif1α(ΔIEC)). 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. Hif1α(ΔIEC) mice still developed lesions but they were smaller than in the Hif1α-floxed siblings (Hif1α(F/F)). Microscopically, Hif1α(ΔIEC) mice had significantly less severe colon inflammation than Hif1α(F/F) mice. Molecular analysis showed reduced MIF expression and increased E-cadherin mRNA expression in the colon of sulindac-treated Hif1α(ΔIEC) mice. However, immunohistochemistry analysis revealed a defect of E-cadherin protein expression in sulindac-treated Hif1α(ΔIEC) mice. Sulindac sulfide treatment in vitro upregulated Hif1α, c-JUN and IL8 expression through the AHR pathway. Taken together, HIF1α expression augments inflammation in

  17. Transcriptomics in ecotoxicology.

    Science.gov (United States)

    Schirmer, Kristin; Fischer, Beat B; Madureira, Danielle J; Pillai, Smitha

    2010-06-01

    The emergence of analytical tools for high-throughput screening of biomolecules has revolutionized the way in which toxicologists explore the impact of chemicals or other stressors on organisms. One of the most developed and routinely applied high-throughput analysis approaches is transcriptomics, also often referred to as gene expression profiling. The transcriptome represents all RNA molecules, including the messenger RNA (mRNA), which constitutes the building blocks for translating DNA into amino acids to form proteins. The entirety of mRNA is a mirror of the genes that are actively expressed in a cell or an organism at a given time. This in turn allows one to deduce how organisms respond to changes in the external environment. In this article we explore how transcriptomics is currently applied in ecotoxicology and highlight challenges and trends.

  18. 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.

  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)

    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. Inhibition of STAT3, FAK and Src mediated signaling reduces cancer stem cell load, tumorigenic potential and metastasis in breast cancer.

    Science.gov (United States)

    Thakur, Ravi; Trivedi, Rachana; Rastogi, Namrata; Singh, Manisha; Mishra, Durga Prasad

    2015-01-01

    Cancer stem cells (CSCs) are responsible for aggressive tumor growth, metastasis and therapy resistance. In this study, we evaluated the effects of Shikonin (Shk) on breast cancer and found its anti-CSC potential. Shk treatment decreased the expression of various epithelial to mesenchymal transition (EMT) and CSC associated markers. Kinase profiling array and western blot analysis indicated that Shk inhibits STAT3, FAK and Src activation. Inhibition of these signaling proteins using standard inhibitors revealed that STAT3 inhibition affected CSCs properties more significantly than FAK or Src inhibition. We observed a significant decrease in cell migration upon FAK and Src inhibition and decrease in invasion upon inhibition of STAT3, FAK and Src. Combined inhibition of STAT3 with Src or FAK reduced the mammosphere formation, migration and invasion more significantly than the individual inhibitions. These observations indicated that the anti-breast cancer properties of Shk are due to its potential to inhibit multiple signaling proteins. Shk also reduced the activation and expression of STAT3, FAK and Src in vivo and reduced tumorigenicity, growth and metastasis of 4T1 cells. Collectively, this study underscores the translational relevance of using a single inhibitor (Shk) for compromising multiple tumor-associated signaling pathways to check cancer metastasis and stem cell load. PMID:25973915

  1. Citrus Fruit Intake Substantially Reduces the Risk of Esophageal Cancer: A Meta-Analysis of Epidemiologic Studies.

    Science.gov (United States)

    Wang, Anqiang; Zhu, Chengpei; Fu, Lilan; Wan, Xueshuai; Yang, Xiaobo; Zhang, Haohai; Miao, Ruoyu; He, Lian; Sang, Xinting; Zhao, Haitao

    2015-09-01

    Many epidemiologic studies indicate a potential association between fruit and vegetable intake and various cancers. The purpose of this meta-analysis is to investigate the association between citrus fruit intake and esophageal cancer risk. The authors conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Library from inception until July 2014. Studies presenting information about citrus intake and esophageal cancer were analyzed. The authors extracted the categories of citrus intake, study-specific odds ratio or relative risk, and the P value and associated 95% confidence intervals for the highest versus lowest dietary intake of citrus fruit level. The association was quantified using meta-analysis of standard errors with a random-effects model. Thirteen case-control studies and 6 cohort studies were eligible for inclusion. Citrus intake may significantly reduce risk of esophageal cancer (summary odds ratio = 0.63; 95% confidence interval = 0.52-0.75; P = 0), without notable publication bias (intercept = -0.79, P = 0.288) and with significant heterogeneity across studies (I = 52%). The results from epidemiologic studies suggest an inverse association between citrus fruit intake and esophageal cancer risk. The significant effect is consistent between case-control and cohort studies. Larger prospective studies with rigorous methodology should be considered to validate the association between citrus fruits and esophageal cancer.

  2. The VEGF_936_C>T 3'UTR polymorphism reduces BRCA1-associated breast cancer risk in Polish women.

    Science.gov (United States)

    Jakubowska, Anna; Gronwald, Jacek; Menkiszak, Janusz; Górski, Bohdan; Huzarski, Tomasz; Byrski, Tomasz; Edler, Lutz; Lubiński, Jan; Scott, Rodney J; Hamann, Ute

    2008-04-01

    The vascular endothelial growth factor (VEGF) plays a crucial role in the initiation of angiogenesis, which is an important stage in tumor development. A functional 936_C>T polymorphism in the VEGF gene and its association with sporadic breast cancer risk has been analyzed in various studies yielding conflicting results. To analyze the role of this polymorphism in modifying hereditary breast and ovarian cancer risks, we conducted a case-control study and genotyped 755 Polish BRCA1 carriers, including 319 breast cancer cases, 146 ovarian cancer cases, and 290 unaffected controls. The results revealed an association of the CT+TT genotypes with a reduced breast cancer risk (OR(adj) 0.63, 95% CI, 0.41-0.98; OR(clustered) 0.63, 95% CI, 0.48-0.83), and a potential effect on ovarian cancer risk (OR(adj) 0.62, 95% CI, 0.33-1.18; OR(clustered) 0.62, 95% CI, 0.47-0.83). Thus, the 936_C>T polymorphism appears to modify disease risks in BRCA1 carriers. PMID:18171601

  3. Upregulation of endogenous ICAM-1 reduces ovarian cancer cell growth in the absence of immune cells

    NARCIS (Netherlands)

    de Groote, Marloes L.; Kazemier, Hinke G.; Huisman, Christian; van der Gun, Bernardina T. F.; Faas, Marijke M.; Rots, Marianne G.

    2014-01-01

    Ovarian cancer is a difficult-to-treat cancer with a 5-year survival rate of only approximate to 45%, due to late diagnosis and therapy resistance. In need of new therapeutic approaches, induction of intercellular adhesion molecule (ICAM)-1 expression might be of interest, since the expression of IC

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

    Science.gov (United States)

    Chen, Ting-Hao; Tung, Tao-Hsin; Chen, Pei-Shih; Wang, Shu-Hui; Chao, Chuang-Min; Hsiung, Nan-Hsing; Chi, Ching-Chi

    2016-01-01

    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. PMID:26884799

  5. 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.

  6. Local and Systemic Therapies for Breast Cancer Patients: Reducing Short-term Symptoms with the Methods of Integrative Medicine

    OpenAIRE

    Hack, C. C.; Voiß, P.; S. Lange; Paul, A. E.; Conrad, S.; Dobos, G J; Beckmann, M. W.; Kümmel, S

    2015-01-01

    With improved prognosis due to advances in the diagnosis and therapy of breast cancer, physicians and therapists now focus on aspects such as quality of life and the management of side effects from breast cancer treatment. Therapy- and disease-related side effects often reduce the patientʼs quality of life and can place a further burden on patients, with non-compliance or discontinuation of therapy a potential consequence. Study data have shown that therapy- and disease-related side effects c...

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

    Directory of Open Access Journals (Sweden)

    Udi Gluschnaider

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  8. Study Protocol: A randomized controlled trial of patient navigation-activation to reduce cancer health disparities

    Directory of Open Access Journals (Sweden)

    Rousseau Sally

    2010-10-01

    Full Text Available Abstract Background Cancer health disparities affecting low-income and minority patients are well documented. Root-causes are multifactorial, including diagnostic and treatment delays, social and financial barriers, and poor communication. Patient navigation and communication coaching (activation are potential interventions to address disparities in cancer treatment. The purpose of this clinical trial is to test the effectiveness of an intervention combining patient navigation and activation to improve cancer treatment. Methods/Design The Rochester Patient Navigation Research Program (PNRP is a National Cancer Institute-sponsored, patient-level randomized trial (RCT of patient navigation and activation, targeting newly-diagnosed breast and colorectal cancer patients in Rochester, NY. The goal of the program is to decrease cancer health disparities by addressing barriers to receipt of cancer care and promoting patient self-efficacy. The intervention uses trained, paraprofessional patient navigators recruited from the target community, and a detailed training and supervisory program. Recruited patients are randomly assigned to receive either usual care (except for baseline and follow-up questionnaires and interviews or intervention. The intervention patients receive tailored assistance from their patient navigators, including phone calls, in-person meetings, and behind-the-scenes coordination of care. A total of 344 patients have been recruited. Outcomes measured at three month intervals include timeliness of care, patient adherence, patient satisfaction, quality of life, self-efficacy, health literacy, and cancer knowledge. Discussion This unique intervention combining patient navigation and patient activation is designed to address the multifactorial problem of cancer health disparities. If successful, this study will affect the design and implementation of patient navigation programs. Trials Registration clinicaltrials.gov identifier NCT

  9. Does Music Therapy Reduce Anxiety and Depression in Cancer Patients? A Systematic Literature Review.

    OpenAIRE

    Moir, Victoria

    2008-01-01

    Background One in three people in England will develop cancer, and one in four will die from it. Providing support for patients experiencing distress is a key component of the role of nurses involved in cancer care. Interest in the potential benefits of complementary therapies in cancer care has grown and is continuing to grow. However, NHS spending is focused on interventions which are both effective and cost-effective, in line with NICE guidance. There is, therefore, a need for up-to-da...

  10. Exercise, Behavioral Therapy Reduce Menopausal Symptoms Caused by Breast Cancer Treatment

    Science.gov (United States)

    Women with breast cancer who were suffering from treatment-related menopausal symptoms experienced symptom relief with cognitive behavioral therapy, physical exercise, or both, according to a Dutch study.

  11. 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 ab

  12. Denosumab Reduces Risk of Bone Side Effects in Advanced Prostate Cancer

    Science.gov (United States)

    The biological agent denosumab (Xgeva) is more effective than zoledronic acid at decreasing the risk of bone fractures and other skeletal-related events (SRE) in men with castration-resistant metastatic prostate cancer, according to results from a randomi

  13. Housework Reduces All-Cause and Cancer Mortality in Chinese Men

    OpenAIRE

    Ruby Yu; Jason Leung; Jean Woo

    2013-01-01

    BACKGROUND: Leisure time physical activity has been extensively studied. However, the health benefits of non-leisure time physical activity, particular those undertaken at home on all-cause and cancer mortality are limited, particularly among the elderly. METHODS: We studied physical activity in relation to all-cause and cancer mortality in a cohort of 4,000 community-dwelling elderly aged 65 and older. Leisure time physical activity (sport/recreational activity and lawn work/yard care/garden...

  14. Reduced risk of colorectal cancer among recent generations in New Zealand.

    OpenAIRE

    Cox, B.; Little, J.

    1992-01-01

    Male and female age standardised mortality and incidence rates of colorectal cancer have increased over the most recent 30 years in New Zealand. Among men and women aged 40 to 74, age standardised mortality and incidence rates increased 18 to 105%. However, age standardised mortality and incidence rates among younger men and women have declined from 14 to 69%. Analysis of trends in age specific mortality and incidence rates indicates that the occurrence of colorectal cancer has been declining...

  15. Increasing awareness of gynecological cancer symptoms and reducing barriers to medical help seeking: does health literacy play a role?

    Science.gov (United States)

    Boxell, Emily M; Smith, Samuel G; Morris, Melanie; Kummer, Sonja; Rowlands, Gill; Waller, Jo; Wardle, Jane; Simon, Alice E

    2012-01-01

    Health literacy may influence the efficacy of print-based public health interventions. A key part of the U.K. cancer control strategy is to provide information to the public on earlier diagnoses with a view to improving the United Kingdom's relatively poor 1-year cancer survival statistics. This study examined the effect of health literacy on the efficacy of a gynecological cancer information leaflet. Participants (n = 451) were recruited from 17 Cancer Research UK events. Health literacy was assessed with the Newest Vital Sign test. Gynecological cancer symptom awareness and barriers to medical help seeking were assessed before and after participants read the leaflet. Symptom awareness improved, and barriers to medical help seeking were reduced (ps .05). As predicted, individuals with lower health literacy benefited less after exposure to the leaflet (ps information design principles in the development of the leaflet, more intensive efforts may be required to ensure that inequalities are not exacerbated by reliance on print-based public health interventions.

  16. Radionuclide (131)I labeled reduced graphene oxide for nuclear imaging guided combined radio- and photothermal therapy of cancer.

    Science.gov (United States)

    Chen, Lei; Zhong, Xiaoyan; Yi, Xuan; Huang, Min; Ning, Ping; Liu, Teng; Ge, Cuicui; Chai, Zhifang; Liu, Zhuang; Yang, Kai

    2015-10-01

    Nano-graphene and its derivatives have attracted great attention in biomedicine, including their applications in cancer theranostics. In this work, we develop 131I labeled, polyethylene glycol (PEG) coated reduced nano-graphene oxide (RGO), obtaining 131I-RGO-PEG for nuclear imaging guided combined radiotherapy and photothermal therapy of cancer. Compared with free 131I, 131IRGO- PEG exhibits enhanced cellular uptake and thus improved radio-therapeutic efficacy against cancer cells. As revealed by gamma imaging, efficient tumor accumulation of 131I-RGO-PEG is observed after its intravenous injection. While RGO exhibits strong near-infrared (NIR) absorbance and could induce effective photothermal heating of tumor under NIR light irradiation, 131I is able to emit high-energy X-ray to induce cancer killing as the result of radio ionization effect. By utilizing the combined photothermal therapy and radiotherapy, both of which are delivered by a single agent 131IRGO- PEG, effective elimination of tumors is achieved in our animal tumor model experiments. Toxicology studies further indicate that 131I-RGO-PEG induces no appreciable toxicity to mice at the treatment dose. Our work demonstrates the great promise of combing nuclear medicine and photothermal therapy as a novel therapeutic strategy to realize synergistic efficacy in cancer treatment. PMID:26188609

  17. Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality

    OpenAIRE

    Xu, Hua; Aldrich, Melinda C; Chen, Qingxia; Liu, Hongfang; Peterson, Neeraja B.; Dai, Qi; Levy, Mia; Shah, Anushi; Han, Xue; Ruan, Xiaoyang; Jiang, Min; Ying LI; Julien, Jamii St.; Warner, Jeremy; Friedman, Carol

    2014-01-01

    Objectives Drug repurposing, which finds new indications for existing drugs, has received great attention recently. The goal of our work is to assess the feasibility of using electronic health records (EHRs) and automated informatics methods to efficiently validate a recent drug repurposing association of metformin with reduced cancer mortality. Methods By linking two large EHRs from Vanderbilt University Medical Center and Mayo Clinic to their tumor registries, we constructed a cohort includ...

  18. 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

    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...... the introduction, and the third interval represents the current situation. The median time from referral to first consultation was reduced from eight calendar days in group 1 to only one day in groups 2 and 3 (p ...

  19. A Walnut-Enriched Diet Reduces the Growth of LNCaP Human Prostate Cancer Xenografts in Nude Mice

    OpenAIRE

    Reiter, Russel J.; Tan, Dun-Xian; Manchester, Lucien C.; Korkmaz, Ahmet; Fuentes-Broto, Lorena; Hardman, W. Elaine; Rosales-Corral, Sergio A; Qi, Wenbo

    2013-01-01

    It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those ...

  20. Reduced LAK cytotoxicity of peripheral blood mononuclear cells in patients with bladder cancer

    DEFF Research Database (Denmark)

    Hermann, G G; Petersen, K R; Steven, K;

    1990-01-01

    were analyzed using monoclonal antibodies against T cells, natural killer (NK) -cells, monocytes, and activation markers. The cytotoxicities of US-PBMC, PS-PBMC, and LAK cells were all significantly lower in the cancer patients than in the controls (P less than 0.05). The percentages of PBMC positive......The cytotoxicity of unstimulated peripheral blood mononuclear cells (US-PBMC), phytohemagglutinin (PHA)-stimulated PBMC (PS-PBMC) and interleukin-2 (IL-2)-activated PBMC (LAK cells) was assessed in patients with noninvasive and invasive transitional-cell bladder cancer and compared with those...... determined in healthy controls. The differences in the cytotoxicities were correlated with specific changes in the subsets of peripheral blood mononuclear cells (PBMC). PBMC from 37 patients and 13 healthy controls were tested against the bladder cancer cell line T24 in 51Cr-release assays. The PBMC subsets...

  1. 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

    .19-1.90) and 1.41 (1.10-1.81). After exclusion of 8 weeks mortality the odds ratios were 1.38 (1.08-1.77) and 1.32 (1.02-1.71). CONCLUSIONS: This nationwide study confirms that patients experiencing anastomotic leakage after gastroesophageal cancer resection have a significantly lower long-term survival, even......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...... and consecutively, nationwide collected patients who underwent gastroesophageal cancer resection between 2003 and 2011 in Denmark. The operation was carried out as an Ivor Lewis procedure. Only patients with intrathoracic anastomosis were included in the analysis. RESULTS: From 2003 to 2011, 1,296 patients...

  2. HPV Literacy and Associated Factors Among Hmong American Immigrants: Implications for Reducing Cervical Cancer Disparity.

    Science.gov (United States)

    Beltran, Raiza; Simms, Tina; Lee, Hee Yun; Kwon, Melissa

    2016-06-01

    Previous studies show that certain minority and ethnic communities experience low human papillomavirus (HPV) vaccination rates despite a higher cervical cancer burden. HPV is known to be responsible for almost all cervical cancer cases. Hmong Americans, a growing Asian American population, appear to be at increased risk. The cervical cancer incidence rate among Hmong American women is three times higher than other Asian/Pacific Islanders and more than four times higher than Non-Hispanic Whites. Despite such alarming statistics, there is limited research focusing on HPV literacy and its associated factors in the Hmong American community. This study's objectives are to investigate: (1) the level of HPV knowledge among Hmong Americans; (2) HPV vaccination initiation and completion rates of Hmong Americans; and (3) factors associated with HPV literacy in the Hmong American community. Andersen's Behavioral Model of Health Services Use was used as the study's theoretical framework. A self-administered paper and online health survey was completed by192 Hmong Americans living in a major metropolitan area in Minnesota. Results revealed a mean score of 4.76 (SD 1.67) for the 7-item questionnaire measuring HPV knowledge. The HPV vaccination initiation rate was 46.3 % (n = 56), with 32.7 % completing the recommended three doses. Multiple regression analysis found that participants' level of education, number of doctor visits, and cervical cancer screening literacy were significantly associated with HPV knowledge. This study's results indicate the important role of health providers in educating Hmong Americans patients about HPV and cervical cancer prevention to decrease the cervical cancer burden in this high-risk population. PMID:26696118

  3. 胃癌基因表达谱和蛋白质表达谱的分析研究%Analysis of human gastric cancer by transcriptome and proteome profiling

    Institute of Scientific and Technical Information of China (English)

    李炜; 刘炳亚; 张晓青; 杨燕青; 李建芳; 唐凯玲; 张庆华; 陈雪华; 朱正纲

    2009-01-01

    Objective To screen differential expression genes and proteins at transcriptome and proteome levels between human gastric cancer tissue and corresponding normal mucosa. Methods Fresh-frozen gastric cancers were collected from patients treated at Ruijin Hospital. A total of 22 pairs of gastric cancer tissues and the corresponding noncancerous mucosa were analyzed. Commercially available cDNA microarray with 14 592 genes/ESTs was used. Genes were considered to be up-or down-regulated when the intensity ratio Cy3/Cy5 was ≥2 or ≤0.5 in over 50% samples (P<0.05). Immobilized pH gradient(IPG)-based 2-DE was applied to separate the total proteins of gastric cancer tissue and paired normal tissue. After staining and analysis by software, the differential expression proteins were identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) or MALDI-TOF-TOF-MS. Results As compared with corresponding noncancerous tisssue, there were totally 149 up-regnlating genes/ESTs and 238 down-regulating genes/ESTs in gastric cancer, including 29 genes with 3-fold over-expression ratio and 21 genes with 5-fold under-expression. Fifteen protein spots were identified successfully, among whom there were ten over-expressed and five under-expressed proteins in gastric cancer tissue compared with normal tissue. Most of over-expressed genes and proteins were related to cell motility, cell proliferation, signal transduction, while those under-expressed genes and proteins were related to defense response, toxicoid metabolism. Conclusion Studying gastric cancer at transcriptome and proteome levels can help demonstrate tumorigenesis and biological characteristics of gastric cancer comprehensively and provide powerful tools to find new biomarkers associated with gastric cancer and therapy targets.%目的 从转录组水平和蛋白质组水平寻找胃癌组织与正常胃组织间的差异表达基因和蛋白.方法 应用含有14592个已知基因

  4. Reduced expression of DNA repair and redox signaling protein APE1/Ref-1 impairs human pancreatic cancer cell survival, proliferation, and cell cycle progression.

    Science.gov (United States)

    Jiang, Yanlin; Zhou, Shaoyu; Sandusky, George E; Kelley, Mark R; Fishel, Melissa L

    2010-11-01

    Pancreatic cancer is a deadly disease that is virtually never cured. Understanding the chemoresistance intrinsic to this cancer will aid in developing new regimens. High expression of APE1/Ref-1, a DNA repair and redox signaling protein, is associated with resistance, poor outcome, and angiogenesis; little is known in pancreatic cancer. Immunostaining of adenocarcinoma shows greater APE1/Ref-1 expression than in normal pancreas tissue. A decrease in APE1/Ref-1 protein levels results in pancreatic cancer cell growth inhibition, increased apoptosis, and altered cell cycle progression. Endogenous cell cycle inhibitors increase when APE1/ Ref-1 is reduced, demonstrating its importance to proliferation and growth of pancreatic cancer.

  5. An integrative transcriptomics approach identifies miR-503 as a candidate master regulator of the estrogen response in MCF-7 breast cancer cells

    Science.gov (United States)

    Purvis, Jeremy E.

    2016-01-01

    Estrogen receptor α (ERα) is an important biomarker of breast cancer severity and a common therapeutic target. In response to estrogen, ERα stimulates a dynamic transcriptional program including both coding and noncoding RNAs. We generate a fine-scale map of expression dynamics by performing a temporal profiling of both messenger RNAs (mRNAs) and microRNAs (miRNAs) in MCF-7 cells (an ER+ model cell line for breast cancer) in response to estrogen stimulation. We identified three primary expression trends—transient, induced, and repressed—that were each enriched for genes with distinct cellular functions. Integrative analysis of mRNA and miRNA temporal expression profiles identified miR-503 as the strongest candidate master regulator of the estrogen response, in part through suppression of ZNF217—an oncogene that is frequently amplified in cancer. We confirmed experimentally that miR-503 directly targets ZNF217 and that overexpression of miR-503 suppresses MCF-7 cell proliferation. Moreover, the levels of ZNF217 and miR-503 are associated with opposite outcomes in breast cancer patient cohorts, with high expression of ZNF217 associated with poor survival and high expression of miR-503 associated with improved survival. Overall, these data indicate that miR-503 acts as a potent estrogen-induced candidate tumor suppressor miRNA that opposes cellular proliferation and has promise as a novel therapeutic for breast cancer. More generally, our work provides a systems-level framework for identifying functional interactions that shape the temporal dynamics of gene expression. PMID:27539783

  6. Transcriptomics using axolotls.

    Science.gov (United States)

    Voss, S Randal; Athippozhy, Antony; Woodcock, M Ryan

    2015-01-01

    Microarray and RNA-sequencing technology now exists for the characterization of the Ambystoma mexicanum transcriptome. With sufficient replication, these tools give the opportunity to truly investigate gene expression in a variety of experimental paradigms. Analysis of data from the Amby002 array and RNA-sequencing technology can identify genes that change expression levels in concert with each other, which in turn may reveal mechanisms associated with biological processes and molecular functions. PMID:25740496

  7. Adaptive radiotherapy for bladder cancer reduces integral dose despite daily volumetric imaging

    International Nuclear Information System (INIS)

    We studied the integral radiation dose in 27 patients who had adaptive radiotherapy for bladder cancer using kilo voltage cone beam CT imaging. Compared to conventional radiotherapy the reduction in margin and choice of best plan of three for the day resulted in a lower total dose in most patients despite daily volumetric imaging.

  8. 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.

  9. A panel of kallikrein markers can reduce unnecessary biopsy for prostate cancer: data from the European Randomized Study of Prostate Cancer Screening in Göteborg, Sweden

    Directory of Open Access Journals (Sweden)

    Scardino Peter T

    2008-07-01

    Full Text Available Abstract Background Prostate-specific antigen (PSA is widely used to detect prostate cancer. The low positive predictive value of elevated PSA results in large numbers of unnecessary prostate biopsies. We set out to determine whether a multivariable model including four kallikrein forms (total, free, and intact PSA, and human kallikrein 2 (hK2 could predict prostate biopsy outcome in previously unscreened men with elevated total PSA. Methods The study cohort comprised 740 men in Göteborg, Sweden, undergoing biopsy during the first round of the European Randomized study of Screening for Prostate Cancer. We calculated the area-under-the-curve (AUC for predicting prostate cancer at biopsy. AUCs for a model including age and PSA (the 'laboratory' model and age, PSA and digital rectal exam (the 'clinical' model were compared with those for models that also included additional kallikreins. Results Addition of free and intact PSA and hK2 improved AUC from 0.68 to 0.83 and from 0.72 to 0.84, for the laboratory and clinical models respectively. Using a 20% risk of prostate cancer as the threshold for biopsy would have reduced the number of biopsies by 424 (57% and missed only 31 out of 152 low-grade and 3 out of 40 high-grade cancers. Conclusion Multiple kallikrein forms measured in blood can predict the result of biopsy in previously unscreened men with elevated PSA. A multivariable model can determine which men should be advised to undergo biopsy and which might be advised to continue screening, but defer biopsy until there was stronger evidence of malignancy.

  10. Transcriptome analysis of copper homeostasis genes reveals coordinated upregulation of SLC31A1,SCO1, and COX11 in colorectal cancer.

    Science.gov (United States)

    Barresi, Vincenza; Trovato-Salinaro, Angela; Spampinato, Giorgia; Musso, Nicolò; Castorina, Sergio; Rizzarelli, Enrico; Condorelli, Daniele Filippo

    2016-08-01

    Copper homeostasis and distribution is strictly regulated by a network of transporters and intracellular chaperones encoded by a group of genes collectively known as copper homeostasis genes (CHGs). In this work, analysis of The Cancer Genome Atlas database for somatic point mutations in colorectal cancer revealed that inactivating mutations are absent or extremely rare in CHGs. Using oligonucleotide microarrays, we found a strong increase in mRNA levels of the membrane copper transporter 1 protein [CTR1; encoded by the solute carrier family 31 member 1 gene (SLC31A1 gene)] in our series of colorectal carcinoma samples. CTR1 is the main copper influx transporter and changes in its expression are able to induce modifications of cellular copper accumulation. The increased SLC31A1 mRNA level is accompanied by a parallel increase in transcript levels for copper efflux pump ATP7A, copper metabolism Murr1 domain containing 1 (COMMD1), the cytochrome C oxidase assembly factors [synthesis of cytochrome c oxidase 1 (SCO1) and cytochrome c oxidase copper chaperone 11 (COX11)], the cupric reductase six transmembrane epithelial antigen of the prostate (STEAP3), and the metal-regulatory transcription factors (MTF1, MTF2) and specificity protein 1 (SP1). The significant correlation between SLC31A1,SCO1, and COX11 mRNA levels suggests that this transcriptional upregulation might be part of a coordinated program of gene regulation. Transcript-level upregulation of SLC31A1,SCO1, and COX11 was also confirmed by the analysis of different colon carcinoma cell lines (Caco-2, HT116, HT29) and cancer cell lines of different tissue origin (MCF7, PC3). Finally, exon-level expression analysis of SLC31A1 reveals differential expression of alternative transcripts in colorectal cancer and normal colonic mucosa.

  11. Transcriptome analysis of copper homeostasis genes reveals coordinated upregulation of SLC31A1,SCO1, and COX11 in colorectal cancer.

    Science.gov (United States)

    Barresi, Vincenza; Trovato-Salinaro, Angela; Spampinato, Giorgia; Musso, Nicolò; Castorina, Sergio; Rizzarelli, Enrico; Condorelli, Daniele Filippo

    2016-08-01

    Copper homeostasis and distribution is strictly regulated by a network of transporters and intracellular chaperones encoded by a group of genes collectively known as copper homeostasis genes (CHGs). In this work, analysis of The Cancer Genome Atlas database for somatic point mutations in colorectal cancer revealed that inactivating mutations are absent or extremely rare in CHGs. Using oligonucleotide microarrays, we found a strong increase in mRNA levels of the membrane copper transporter 1 protein [CTR1; encoded by the solute carrier family 31 member 1 gene (SLC31A1 gene)] in our series of colorectal carcinoma samples. CTR1 is the main copper influx transporter and changes in its expression are able to induce modifications of cellular copper accumulation. The increased SLC31A1 mRNA level is accompanied by a parallel increase in transcript levels for copper efflux pump ATP7A, copper metabolism Murr1 domain containing 1 (COMMD1), the cytochrome C oxidase assembly factors [synthesis of cytochrome c oxidase 1 (SCO1) and cytochrome c oxidase copper chaperone 11 (COX11)], the cupric reductase six transmembrane epithelial antigen of the prostate (STEAP3), and the metal-regulatory transcription factors (MTF1, MTF2) and specificity protein 1 (SP1). The significant correlation between SLC31A1,SCO1, and COX11 mRNA levels suggests that this transcriptional upregulation might be part of a coordinated program of gene regulation. Transcript-level upregulation of SLC31A1,SCO1, and COX11 was also confirmed by the analysis of different colon carcinoma cell lines (Caco-2, HT116, HT29) and cancer cell lines of different tissue origin (MCF7, PC3). Finally, exon-level expression analysis of SLC31A1 reveals differential expression of alternative transcripts in colorectal cancer and normal colonic mucosa. PMID:27516958

  12. Engaging African Americans in developing an intervention to reduce breast cancer recurrence: A brief report

    Science.gov (United States)

    Smith, Selina A.; Whitehead, Mary S.; Sheats, Joyce Q.; Fontenot, Brittney; Alema-Mensah, Ernest; Ansa, Benjamin

    2016-01-01

    Background To develop a culturally appropriate lifestyle intervention, involvement of its intended users is needed. Methods Members of an African American (AA) breast cancer support group participated in two 4-hour guided discussions, which were audiotaped, transcribed, and analyzed to guide the content. Results The support group collaborated with researchers to develop 24 experiential nutrition education sessions using a social cognitive framework and incorporating self-regulation skills (goal-setting, self-monitoring, problem-solving, stimulus control) and social support to enhance self-efficacy for changes in dietary intake. Conclusions Community engagement fostered autonomy, built collaboration, and enhanced the capacity of AA breast cancer survivors to participate in developing a lifestyle intervention.

  13. Triple Negative Breast Cancers Have a Reduced Expression of DNA Repair Genes

    Science.gov (United States)

    Andreis, Daniele; Bertoni, Ramona; Giardini, Roberto; Fox, Stephen B.; Broggini, Massimo; Bottini, Alberto; Zanoni, Vanessa; Bazzola, Letizia; Foroni, Chiara; Generali, Daniele; Damia, Giovanna

    2013-01-01

    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. PMID:23825533

  14. Transcriptomic studies on liver toxicity of acetaminophen.

    Science.gov (United States)

    Toska, Endrit; Zagorsky, Robert; Figler, Bryan; Cheng, Feng

    2014-09-01

    Acetaminophen is widely used as a pain reliever and to reduce fever. At high doses, it can cause severe hepatotoxicity. Acetaminophen overdose has become the leading cause of acute liver failure in the US. The mechanisms for acetaminophen-induced liver injury are unclear. Transcriptomic studies can identify the changes in expression of thousands of genes when exposed to supratherapeutic doses of acetaminophen. These studies elucidated the mechanism of acetaminophen-induced hepatotoxicity and also provide insight into future development of diagnosis and treatment options for acetaminophen-induced acute liver failure. The following is a brief overview of some recent transcriptomic studies and gene-expression-based prediction models on liver toxicity induced by acetaminophen.

  15. 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.

  16. Gut microbiota-derived propionate reduces cancer cell proliferation in the liver

    OpenAIRE

    Bindels, Laure B.; Porporato, Paolo; Dewulf, Evelyne; Verrax, Julien; Audrey M Neyrinck; Martin, J C; Scott, K P; Buc Calderon, Pedro; Feron, Olivier; Muccioli, Giulio; Sonveaux, Pierre; Cani, Patrice D.; Delzenne, Nathalie M

    2012-01-01

    BACKGROUND: Metabolites released by the gut microbiota may influence host metabolism and immunity. We have tested the hypothesis that inulin-type fructans (ITF), by promoting microbial production of short-chain fatty acids (SCFA), influence cancer cell proliferation outside the gut. METHODS: Mice transplanted with Bcr-Abl-transfected BaF3 cells, received ITF in their drinking water. Gut microbiota was analysed by 16S rDNA polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis...

  17. Radiotherapy for Rectal Cancer Is Associated With Reduced Serum Testosterone and Increased FSH and LH

    International Nuclear Information System (INIS)

    Purpose: It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. Methods and Materials: All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone binding globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. Results: Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. Conclusions: Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction

  18. 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.

  19. 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

  20. Reduced arginine availability and nitric oxide synthesis in cancer is related to impaired endogenous arginine synthesis.

    Science.gov (United States)

    Engelen, Mariëlle P K J; Safar, Ahmed M; Bartter, Thaddeus; Koeman, Fari; Deutz, Nicolaas E P

    2016-07-01

    Reduced plasma arginine (ARG) concentrations are found in various types of cancer. ARG and its product nitric oxide (NO) are important mediators in the immune function and the defense against tumour cells. It remains unclear whether the diminished systemic ARG availability in cancer is related to insufficient endogenous ARG synthesis, negatively affecting NO synthesis, and whether a dietary amino acid mixture is able to restore this. In 13 patients with advanced non-small cell lung cancer (NSCLC) and 11 healthy controls, whole body ARG and CIT (citrulline) rates of appearance were measured by stable isotope methodology before and after intake of a mixture of amino acids as present in whey protein. The conversions of CIT to ARG (indicator of de novo ARG synthesis) and ARG to CIT (marker of NO synthesis), and ARG clearance (reflecting ARG disposal capacity) were calculated. Plasma isotopic enrichments and amino acid concentrations were measured by LC-MS/MS. Conversions of CIT to ARG and ARG to CIT (P<0.05), and CIT rate of appearance (P=0.07) were lower in NSCLC. ARG rate of appearance and clearance were comparable suggesting no enhanced systemic ARG production and disposal capacity in NSCLC. After intake of the mixture, ARG rate of appearance and concentration increased (P<0.001), and ARG to CIT conversion was restored in NSCLC. In conclusion, an impaired endogenous ARG synthesis plays a role in the reduced systemic ARG availability and NO synthesis in advanced NSCLC. Nutritional approaches may restore systemic ARG availability and NO synthesis in cancer, but the clinical implication remains unclear. PMID:27129191

  1. Reducing Both Pgp Overexpression and Drug Efflux with Anti-Cancer Gold-Paclitaxel Nanoconjugates

    Science.gov (United States)

    Li, Fei; Zhou, Xiaofei; Zhou, Hongyu; Jia, Jianbo; Li, Liwen; Zhai, Shumei; Yan, Bing

    2016-01-01

    Repeated administrations of anti-cancer drugs to patients often induce drug resistance. P-glycoprotein (Pgp) facilitates an efficient drug efflux, preventing cellular accumulation of drugs and causing multi-drug resistance (MDR). In this study, we developed a gold-paclitaxel nanoconjugate system to overcome MDR. Gold nanoparticles (GNPs) were conjugated with β-cyclodextrin enclosing paclitaxel (PTX) molecules and PEG molecules. GNP conjugates were effectively endocytosed by both drug-sensitive human lung cancer H460 cells and Pgp-overexpressed drug-resistant H460PTX cells. Compared with PTX, PGNPs did not induce the Pgp overexpression in drug-sensitive H460 cells after long-term treatment and also avoided being pumped out of cells by overexpressed Pgp molecules in H460PTX with a 17-fold lower EC50 compared to PTX. Fluorescent microscopy and flow cytometry further confirmed that fluorescent labeled PGNPs (f-PGNPs) maintained a high cellular PTX level in both H460 and H460PTX cells. These results demonstrated that nano-drug conjugates were able to avoid the development of drug resistance in sensitive cells and evade Pgp-mediated drug resistance and to maintain a high cytotoxicity in drug-resistant cancer cells. These findings exemplify a powerful nanotechnological approach to the long-lasting issue of chemotherapy-induced drug resistance. PMID:27467397

  2. Diagnosis and treatment of cancer: radiopharmaceutical biochemical markers and therapy with radionuclides and reducing agents

    International Nuclear Information System (INIS)

    The cancer is the Second cause but common of death in many countries like it USES, after the cardiac disease, similar situation in Uruguay. The cancer incidence increasing with the age . I number adult developed the illness. For it, you prove biochemical of laboratory, through their determination in the serum or in the plasma, They are very useful in the patient's care with cancer. It is so the mensuration of resulting substances of the cellular metabolism that they are overturned to the patient's sanguine torrent with a certain neoplasms, it is constituted in markers of the illness, called by it Markers Tumours. Many of these labels are useful in the neoplasmas neodiagnosis and therapy. However, in general, any of the labels of it own can not be used for all neoplasms types and for all patients with kind of disease. The most effective uses in the labels tumour have been, the pursuit of the answers to the treatment and the identification of the early recurrence

  3. Reducing Both Pgp Overexpression and Drug Efflux with Anti-Cancer Gold-Paclitaxel Nanoconjugates.

    Science.gov (United States)

    Li, Fei; Zhou, Xiaofei; Zhou, Hongyu; Jia, Jianbo; Li, Liwen; Zhai, Shumei; Yan, Bing

    2016-01-01

    Repeated administrations of anti-cancer drugs to patients often induce drug resistance. P-glycoprotein (Pgp) facilitates an efficient drug efflux, preventing cellular accumulation of drugs and causing multi-drug resistance (MDR). In this study, we developed a gold-paclitaxel nanoconjugate system to overcome MDR. Gold nanoparticles (GNPs) were conjugated with β-cyclodextrin enclosing paclitaxel (PTX) molecules and PEG molecules. GNP conjugates were effectively endocytosed by both drug-sensitive human lung cancer H460 cells and Pgp-overexpressed drug-resistant H460PTX cells. Compared with PTX, PGNPs did not induce the Pgp overexpression in drug-sensitive H460 cells after long-term treatment and also avoided being pumped out of cells by overexpressed Pgp molecules in H460PTX with a 17-fold lower EC50 compared to PTX. Fluorescent microscopy and flow cytometry further confirmed that fluorescent labeled PGNPs (f-PGNPs) maintained a high cellular PTX level in both H460 and H460PTX cells. These results demonstrated that nano-drug conjugates were able to avoid the development of drug resistance in sensitive cells and evade Pgp-mediated drug resistance and to maintain a high cytotoxicity in drug-resistant cancer cells. These findings exemplify a powerful nanotechnological approach to the long-lasting issue of chemotherapy-induced drug resistance. PMID:27467397

  4. 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

  5. Consumption of fruit and vegetables reduces risk of pancreatic cancer: evidence from epidemiological studies.

    Science.gov (United States)

    Wu, Qi-Jun; Wu, Lang; Zheng, Li-Qiang; Xu, Xin; Ji, Chao; Gong, Ting-Ting

    2016-05-01

    Observational studies have reported inconsistent results on the association between fruit and vegetable intake and the risk of pancreatic cancer. We carried out a meta-analysis of epidemiological studies to summarize available evidence. We searched PubMed, Scopus, and ISI Web of Science databases for relevant studies published until the end of January 2015. Fixed-effects and random-effects models were used to estimate the summary relative risks (RRs) and 95% confidence intervals (CIs) for the associations between fruit and vegetable intake and the risk of pancreatic cancer. A total of 15 case-control studies, eight prospective studies, and one pooled analysis fulfilled the inclusion criteria. The summary RR for the highest versus the lowest intake was 0.73 (95% CI=0.53-1.00) for fruit and vegetables, 0.73 (95% CI=0.63-0.84) for fruit, and 0.76 (95% CI=0.69-0.83) for vegetables, with significant heterogeneities (I=70.5, 55.7, and 43.0%, respectively). Inverse associations were observed in the stratified analysis by study design, although the results of prospective studies showed borderline significance, with corresponding RR=0.90 (95% CI=0.77-1.05) for fruit and vegetable intake, 0.93 (95% CI=0.83-1.03) for fruit intake, and 0.89 (95% CI=0.80-1.00) for vegetable intake. Besides, significant inverse associations were observed in the majority of other subgroup analyses by study quality, geographic location, exposure assessment method, and adjustment for potential confounders. Findings from the present meta-analysis support that fruit and vegetable intake is associated inversely with the risk of pancreatic cancer. However, study design may play a key role in the observed magnitude of the aforementioned association. Future well-designed prospective studies are warranted to confirm these findings.

  6. Investigating VMAT planning technique to reduce rectal and bladder dose in prostate cancer treatment plans

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    Suresh B Rana

    2013-01-01

    Full Text Available Background: RapidArc is a volumetric modulated arc therapy (VMAT technique that can deliver conformal dose distribution to the target while minimizing dose to critical structures. The main purpose of this study was to compare dosimetric quality of full double arc (full DA, full single arc (full SA, and partial double arc (partial DA techniques in RapidArc planning of prostate cancer. Materials and Methods: Twelve cases of prostate cancer involving seminal vesicles were selected for this retrospective study. For each case, RapidArc plans were created using full DA (two full arcs, full SA (one full arc, and partial DA (two partial arcs with anterior and posterior avoidance sectors techniques. For planning target volume (PTV, the maximum and mean doses, conformity, and inhomogeneity indices were evaluated. For bladder and rectum, volumes that received 70, 50, 40, and 20 Gy (V 70Gy , V 50Gy , V 40Gy and V 20Gy , respectively, and mean dose were compared. For femoral heads, V 40Gy , V 20Gy , and mean dose were evaluated. Additionally, an integral dose and monitor units (MUs were compared for each treatment plan. Results: In comparison to full DA and full SA techniques, the partial DA technique was better in sparing of rectum and bladder but delivered higher femoral head dose, which was nonetheless within the planning criteria. No clear dosimetric differences were found between full DA and partial DA plans for dose conformity and target homogeneity. The number of MUs and integral dose were largest with the partial DA technique and lowest with the full SA technique. Conclusion: The partial DA technique provides an alternative RapidArc planning approach for low risk prostate cancer.

  7. relA over-expression reduces tumorigenicity and activates apoptosis in human cancer cells

    OpenAIRE

    Ricca, A; Biroccio, A; Trisciuoglio, D; M. Cippitelli; Zupi, G.; Bufalo, D Del

    2001-01-01

    We previously demonstrated that bcl-2 over-expression increases the malignant behaviour of the MCF7 ADR human breast cancer cell line and enhances nuclear factor-kappa B (NF-k B) transcriptional activity. Here, we investigated the direct effect of increased NF-k B activity on the tumorigenicity of MCF7 ADR cells by over-expressing the NF-k B subunit relA/p65. Surprisingly, our results demonstrated that over-expression of relA determines a considerable reduction of the tumorigenic ability in n...

  8. Inorganic sulfur reduces the motility and invasion of MDA-MB-231 human breast cancer cells

    OpenAIRE

    Kim, Jin Joo; Ha, Ae Wha; Kim, Hee Sun; Kim, Woo Kyoung

    2011-01-01

    This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 µmol/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 µmol/L within 48 h. Inorganic sulfur significantly d...

  9. TCW: transcriptome computational workbench.

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    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

  10. 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. PMID:17030099

  11. Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients

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    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.

  12. 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.

  13. Progressive Muscle Relaxation: An adjuvant therapy for reducing pain and fatigue among hospitalized cancer patients’ receiving radiotherapy.

    Directory of Open Access Journals (Sweden)

    Pragya Pathak

    2013-03-01

    Full Text Available Background: Cancer patients’ face number of problems, among those pain and fatigue are common problems. To manage pain and fatigue among cancer patients, studies now a days are even focusing on use of non-pharmacological/ non invasive methods as exercises, imagery etc. But studies on effect of progressive muscle relaxation (PMR exercises on pain and fatigue among admitted patients are scarce. Objective: The study was done to evaluate effectiveness of PMR exercises on pain and fatigue among hospitalized cancer patients’ receiving radiotherapy. Methods: The study design was quasi-experimental Pre test Post test control group design. Total of 100 participants, 50 in each intervention and control group were included. The subjects in the intervention group received four PMR exercise sessions in 4weeks along with routine standardized treatment while subjects in control group received treatment as usual with no added intervention. Results: There was significant difference (p<0.01 in Pre NPRS (4.42±2.35 to post NPRS (3.44±2.05 scores among intervention group (PMR. Pre assessment mean fatigue scores (CFS of subjects were 33.80±10.62 in intervention group (PMR and 33.24±7.02 in controls where as post assessment CFS were 28.52±12.74 and 36.52±7.53 in intervention and control group respectively. There was significant (p<0.01 reduction in pre to post CFS in PMR group while fatigue increased significantly (p<0.01 in control group. Conclusion: PMR along with routine standard treatment is effective in reducing pain and fatigue among hospitalized cancer patients receiving radiotherapy.

  14. Vitamin intake reduce the risk of gastric cancer: meta-analysis and systematic review of randomized and observational studies.

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    Pengfei Kong

    Full Text Available 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.

  15. 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 ...

  16. Reduced Expression of TFF1 and Increased Expression of TFF3 in Gastric Cancer: Correlation with Clinicopathological Parameters and Prognosis

    Directory of Open Access Journals (Sweden)

    Soyoung Im, Changyoung Yoo, Ji-Han Jung, Hyun Joo Choi, Jinyoung Yoo, Chang Suk Kang

    2013-01-01

    Full Text Available Objectives: The trefoil factor family (TFF is composed of three thermostable, and protease-resistant proteins, named TFF1, TFF2 and TFF3, and plays a role in gastrointestinal mucosal defence and repair. Recently, TFFs have been found to be related to the development of various types of cancer. This study assessed the relationship between the expression of TFF1 and TFF3 and the clinicopathological parameters in gastric carcinoma (GC. Materials and Methods: The expression of TFF1 and TFF3 was analyzed by immunohistochemistry in 292 GCs and 20 normal gastric tissues. Results: All normal gastric tissues expressed TFF1, but 53.8% of GCs showed reduced TFF1 expression. However, TFF3 was not detected in normal gastric tissues and 44.2% of GCs showed a high level of expression. Highly expressed TFF3 was significantly correlated with lymph node metastasis, lymphatic invasion, vein invasion, and advanced stage. The overall survival was shorter in patients with high expression of TFF3 than in those with low expression of TFF3 in 292 GCs and in 125 early GCs (EGCs. Moreover, in patients with EGCs, high expression of TFF3, associated with reduced expression of TFF1, was determined as an independent poor prognostic marker. Conclusions: Reduced expression of TFF1 and increased expression of TFF3 may play a role in the carcinogenesis of gastric cancer. Furthermore, high expression of TFF3 with reduced expression of TFF1 may be a marker of poor prognosis for patients with EGC.

  17. miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity.

    Science.gov (United States)

    O'Brien, Keith; Lowry, Michelle C; Corcoran, Claire; Martinez, Vanesa G; Daly, Melissa; Rani, Sweta; Gallagher, William M; Radomski, Marek W; MacLeod, Roderick A F; O'Driscoll, Lorraine

    2015-10-20

    Exosomes (EVs) have relevance in cell-to-cell communication carrying pro-tumorigenic factors that participate in oncogenesis and drug resistance and are proposed to have potential as self-delivery systems. Advancing on our studies of EVs in triple-negative breast cancer, here we more comprehensively analysed isogenic cell line variants and their EV populations, tissues cell line variants and their EV populations, as well as breast tumour and normal tissues. Profiling 384 miRNAs showed EV miRNA content to be highly representative of their cells of origin. miRNAs most substantially down-regulated in aggressive cells and their EVs originated from 14q32. Analysis of miR-134, the most substantially down-regulated miRNA, supported its clinical relevance in breast tumours compared to matched normal breast tissue. Functional studies indicated that miR-134 controls STAT5B which, in turn, controls Hsp90. miR-134 delivered by direct transfection into Hs578Ts(i)8 cells (in which it was greatly down-regulated) reduced STAT5B, Hsp90, and Bcl-2 levels, reduced cellular proliferation, and enhanced cisplatin-induced apoptosis. Delivery via miR-134-enriched EVs also reduced STAT5B and Hsp90, reduced cellular migration and invasion, and enhanced sensitivity to anti-Hsp90 drugs. While the differing effects achieved by transfection or EV delivery are likely to be, at least partly, due to specific amounts of miR-134 delivered by these routes, these EV-based studies identified miRNA-134 as a potential biomarker and therapeutic for breast cancer. PMID:26416415

  18. High intake of folate from food sources is associated with reduced risk of esophageal cancer in an Australian population.

    Science.gov (United States)

    Ibiebele, Torukiri I; Hughes, Maria Celia; Pandeya, Nirmala; Zhao, Zhen; Montgomery, Grant; Hayward, Nick; Green, Adèle C; Whiteman, David C; Webb, Penelope M

    2011-02-01

    Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barrett's esophagus (BE), a precancerous lesion, remain unexplored. We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC.

  19. A Novel Dose Constraint to Reduce Xerostomia in Head-and-Neck Cancer Patients Treated With Intensity-Modulated Radiotherapy

    International Nuclear Information System (INIS)

    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.

  20. Dexamethasone reduces sensitivity to cisplatin by blunting p53-dependent cellular senescence in non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Haiyan Ge

    Full Text Available INTRODUCTION: Dexamethasone (DEX co-treatment has proved beneficial in NSCLC patients, improving clinical symptoms by the reduction of side effects after chemotherapy. However, recent studies have shown that DEX could render cancer cells more insensitive to cytotoxic drug therapy, but it is not known whether DEX co-treatment could influence therapy-induced senescence (TIS, and unknown whether it is in a p53-dependent or p53-independent manner. METHODS: We examined in different human NSCLC cell lines and detected cellular senescence after cisplatin (DDP treatment in the presence or absence of DEX. The in vivo effect of the combination of DEX and DDP was assessed by tumor growth experiments using human lung cancer cell lines growing as xenograft tumors in nude mice. RESULTS: Co-treatment with DEX during chemotherapy in NSCLC resulted in increased tumor cell viability and inhibition of TIS compared with DDP treated group. DEX co-treatment cells exhibited the decrease of DNA damage signaling pathway proteins, the lower expression of p53 and p21(CIP1, the lower cellular secretory program and down-regulation of NF-κB and its signaling cascade. DEX also significantly reduced DDP sensitivity in vivo. CONCLUSIONS: Our results underscore that DEX reduces chemotherapy sensitivity by blunting therapy induced cellular senescence after chemotherapy in NSCLC, which may, at least in part, in a p53-dependent manner. These data therefore raise concerns about the widespread combined use of gluocorticoids (GCs with antineoplastic drugs in the clinical management of cancer patients.

  1. 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.

  2. Everybody's talking: using entertainment-education video to reduce barriers to discussion of cervical cancer screening among Thai women.

    Science.gov (United States)

    Love, G D; Mouttapa, Michele; Tanjasiri, S P

    2009-10-01

    Although Southeast Asian women are at exceedingly high risk for cervical cancer, low rates of the Pap testing necessary for early detection and successful treatment continue among this group. Previous research suggests that discussions about Pap testing with important people in a woman's life, particularly her doctor, may increase the likelihood of screening; therefore increasing women's discussions about cancer screenings is an important step toward behavior change. The purpose of this study was to determine the effectiveness of a culturally sensitive, seven-minute video intervention in reducing barriers to discussions about Pap tests among Thai women. This unique video presented Thai actors, speaking in Thai, in a soap opera format. Participants completed a self-report questionnaire at baseline, immediately after the intervention and at 3-month follow-up. The comparison group received an educational pamphlet. Although the results indicated that both groups experienced reductions in barriers to communicating with others about Pap tests, the intervention group had significantly stronger outcomes than the comparison group for communicating about Pap tests in general as well as to doctors. These findings suggest that intermediate communication effects such as self-efficacy, collective efficacy and perhaps interpersonal communication may reduce barriers to discussion and positive decision making regarding Pap tests.

  3. 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 BACKGROUND: 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. METHODS: 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. FINDINGS: 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]. CONCLUSIONS: 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.

  4. Hydroxyethyl starch 200/0.5 decreases circulating tumor cells of colorectal cancer patients and reduces metastatic potential of colon cancer cell line through inhibiting platelets activation.

    Science.gov (United States)

    Liang, Hua; Yang, Chengxiang; Zhang, Bin; Wang, Hanbing; Liu, Hongzhen; Zhao, Zhenlong; Zhang, Zhiming; Wen, Xianjie; Lai, Xiaohong

    2015-05-01

    Platelets play an important role in metastasis of circulating tumor cells (CTCs). It has been demonstrated that hydroxyethyl starch (HES) inhibits platelets function. However, the effect of HES on CTCs in patients with colorectal cancer remains unclear. We compared the effects of HES 200/0.5 and HES 130/0.4 on CTCs and platelets activation of colorectal patients in this study. Additionally, the effects of HES 200/0.5 or HES 130/0.4 on metastasis ability of colon cancer cell line that stimulated by activated platelets have been explored. In vivo, 90 patients undergoing colorectal cancer radical surgery received randomly 15 mL/kg of HES 200/0.5 (n = 45) or HES 130/0.4 (n = 45) infusion before surgery. Platelet glycoprotein IIb/IIIa (GPIIb/IIIa), CD62P and platelets aggregation rate (PAR) were evaluated pre-, intra- and postoperatively. Cytokeratin-20 (CK-20) mRNA was detected by reverse transcriptase polymerase chain reaction before and after surgery. In vitro, colon cancer SW480 cells were incubated with activated platelets in the presence or absence HES 200/0.5 or HES 130/0.4. The metastasis ability of SW480 cells was assessed by Transwell assay. The results showed that CK-20 mRNA positive rate in HES 200/0.5 group after surgery was decreased significantly as compared to group HES 130/0.4 (χ (2) = 6.164, P = 0.013). Simultaneously, a more pronounced inhibition of platelets activation was observed in group HES 200/0.5. A positive correlation between platelets activation marker and CK-20 mRNA positive rate was found. In vitro, HES 200/0.5, but not HES 130/0.4, decreased the invasion and migration ability of SW480 cells that induced by activated platelets. Besides, the expression of GPIIb/IIIa, CD62P and PAR was inhibited more strongly in group HES 200/0.5 than those in group HES 130/0.4. In summary, we found that HES 200/0.5 significantly decreased CTCs of patients undergoing colorectal cancer radical surgery as compared to HES 130/0.4, which might be associated

  5. Statins Attenuate Helicobacter pylori CagA Translocation and Reduce Incidence of Gastric Cancer: In Vitro and Population-Based Case-Control Studies.

    Science.gov (United States)

    Lin, Chun-Jung; Liao, Wei-Chih; Lin, Hwai-Jeng; Hsu, Yuan-Man; Lin, Cheng-Li; Chen, Yu-An; Feng, Chun-Lung; Chen, Chih-Jung; Kao, Min-Chuan; Lai, Chih-Ho; Kao, Chia-Hung

    2016-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide. The correlation of Helicobacter pylori and the etiology of gastric cancer was substantially certain. Cholesterol-rich microdomains (also called lipid rafts), which provide platforms for signaling, are associated with H. pylori-induced pathogenesis leading to gastric cancer. Patients who have been prescribed statins, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, have exhibited a reduced risk of several types of cancer. However, no studies have addressed the effect of statins on H. pylori-associated gastric cancer from the antineoplastic perspective. In this study, we showed that treatment of gastric epithelial cells with simvastatin reduced the level of cellular cholesterol and led to attenuation of translocation and phosphorylation of H. pylori cytotoxin-associated gene A (CagA), which is recognized as a major determinant of gastric cancer development. Additionally, a nationwide case-control study based on data from the Taiwanese National Health Insurance Research Database (NHIRD) was conducted. A population-based case-control study revealed that patients who used simvastatin exhibited a significantly reduced risk of gastric cancer (adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.70-0.83). In patients exhibiting H. pylori infection who were prescribed simvastatin, the adjusted OR for gastric cancer was 0.25 (95% CI = 0.12-0.50). Our results combined an in vitro study with a nationwide population analysis reveal that statin use might be a feasible approach to prevent H. pylori-associated gastric cancer.

  6. Statins Attenuate Helicobacter pylori CagA Translocation and Reduce Incidence of Gastric Cancer: In Vitro and Population-Based Case-Control Studies.

    Directory of Open Access Journals (Sweden)

    Chun-Jung Lin

    Full Text Available Gastric cancer is the second leading cause of cancer-related death worldwide. The correlation of Helicobacter pylori and the etiology of gastric cancer was substantially certain. Cholesterol-rich microdomains (also called lipid rafts, which provide platforms for signaling, are associated with H. pylori-induced pathogenesis leading to gastric cancer. Patients who have been prescribed statins, inhibitors of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA reductase, have exhibited a reduced risk of several types of cancer. However, no studies have addressed the effect of statins on H. pylori-associated gastric cancer from the antineoplastic perspective. In this study, we showed that treatment of gastric epithelial cells with simvastatin reduced the level of cellular cholesterol and led to attenuation of translocation and phosphorylation of H. pylori cytotoxin-associated gene A (CagA, which is recognized as a major determinant of gastric cancer development. Additionally, a nationwide case-control study based on data from the Taiwanese National Health Insurance Research Database (NHIRD was conducted. A population-based case-control study revealed that patients who used simvastatin exhibited a significantly reduced risk of gastric cancer (adjusted odds ratio (OR = 0.76, 95% confidence interval (CI = 0.70-0.83. In patients exhibiting H. pylori infection who were prescribed simvastatin, the adjusted OR for gastric cancer was 0.25 (95% CI = 0.12-0.50. Our results combined an in vitro study with a nationwide population analysis reveal that statin use might be a feasible approach to prevent H. pylori-associated gastric cancer.

  7. 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.

  8. Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced

    Directory of Open Access Journals (Sweden)

    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.

  9. Whole Genome and Transcriptome Sequencing of a B3 Thymoma

    OpenAIRE

    Iacopo Petrini; Arun Rajan; Trung Pham; Donna Voeller; Sean Davis; James Gao; Yisong Wang; Giuseppe Giaccone

    2013-01-01

    Molecular pathology of thymomas is poorly understood. Genomic aberrations are frequently identified in tumors but no extensive sequencing has been reported in thymomas. Here we present the first comprehensive view of a B3 thymoma at whole genome and transcriptome levels. A 55-year-old Caucasian female underwent complete resection of a stage IVA B3 thymoma. RNA and DNA were extracted from a snap frozen tumor sample with a fraction of cancer cells over 80%. We performed array comparative genomi...

  10. Metformin and Rapamycin Reduce Pancreatic Cancer Growth in Obese Prediabetic Mice by Distinct MicroRNA-Regulated Mechanisms.

    Science.gov (United States)

    Cifarelli, Vincenza; Lashinger, Laura M; Devlin, Kaylyn L; Dunlap, Sarah M; Huang, Jennifer; Kaaks, Rudolf; Pollak, Michael N; Hursting, Stephen D

    2015-05-01

    Metformin treatment is associated with a decreased risk and better prognosis of pancreatic cancer (PC) in patients with type 2 diabetes, but the mechanism of metformin's PC growth inhibition in the context of a prediabetic state is unknown. We used a Panc02 pancreatic tumor cell transplant model in diet-induced obese (DIO) C57BL/6 mice to compare the effects of metformin and the direct mammalian target of rapamycin (mTOR) inhibitor rapamycin on PC growth, glucose regulation, mTOR pathway signaling, and candidate microRNA (miR) expression. In DIO/prediabetic mice, metformin and rapamycin significantly reduced pancreatic tumor growth and mTOR-related signaling. The rapamycin effects centered on decreased mTOR-regulated growth and survival signaling, including increased expression of let-7b and cell cycle-regulating miRs. Metformin (but not rapamycin) reduced glucose and insulin levels and expression of miR-34a and its direct targets Notch, Slug, and Snail. Metformin also reduced the number and size of Panc02 tumor spheres in vitro and inhibited the expression of Notch in spheroids. Our results suggest that metformin and rapamycin can both inhibit pancreatic tumor growth in obese, prediabetic mice through shared and distinct mechanisms. Metformin and direct mTOR inhibitors, alone or possibly in combination, represent promising intervention strategies for breaking the diabetes-PC link. PMID:25576058

  11. A new approach to reduce toxicities and to improve bioavailabilities of platinum-containing anti-cancer nanodrugs.

    Science.gov (United States)

    Liu, Li; Ye, Qing; Lu, Maggie; Lo, Ya-Chin; Hsu, Yuan-Hung; Wei, Ming-Cheng; Chen, Yu-Hsiang; Lo, Shen-Chuan; Wang, Shian-Jy; Bain, Daniel J; Ho, Chien

    2015-01-01

    Platinum (Pt) drugs are the most potent and commonly used anti-cancer chemotherapeutics. Nanoformulation of Pt drugs has the potential to improve the delivery to tumors and reduce toxic side effects. A major challenge for translating nanodrugs to clinical settings is their rapid clearance by the reticuloendothelial system (RES), hence increasing toxicities on off-target organs and reducing efficacy. We are reporting that an FDA approved parenteral nutrition source, Intralipid 20%, can help this problem. A dichloro (1, 2-diaminocyclohexane) platinum (II)-loaded and hyaluronic acid polymer-coated nanoparticle (DACHPt/HANP) is used in this study. A single dose of Intralipid (2 g/kg, clinical dosage) is administrated [intravenously (i. v.), clinical route] one hour before i.v. injection of DACHPt/HANP. This treatment can significantly reduce the toxicities of DACHPt/HANP in liver, spleen, and, interestingly, kidney. Intralipid can decrease Pt accumulation in the liver, spleen, and kidney by 20.4%, 42.5%, and 31.2% at 24-hr post nanodrug administration, respectively. The bioavailability of DACHPt/HANP increases by 18.7% and 9.4% during the first 5 and 24 hr, respectively. PMID:26039249

  12. A new angiographic imaging platform reduces radiation exposure for patients with liver cancer treated with transarterial chemoembolization

    Energy Technology Data Exchange (ETDEWEB)

    Schernthaner, Ruediger E.; Duran, Rafael; Chapiro, Julius; Wang, Zhijun; Geschwind, Jean-Francois H. [The Johns Hopkins Hospital, Russell H. Morgan Department of Radiology and Radiological Science, Division of Vascular and Interventional Radiology, Baltimore, MD (United States); Lin, MingDe [Ultrasound Imaging and and Interventions (UII), Philips Research North America, Briarcliff Manor, NY (United States)

    2015-11-15

    To quantify the reduction of radiation liver cancer patients are exposed to during transarterial chemoembolization (TACE), while maintaining diagnostic image quality, using a new C-arm imaging platform. In this prospective, HIPAA-compliant, IRB-approved, two-arm trial, 78 consecutive patients with primary or secondary liver cancer were treated with TACE on a C-arm imaging platform before and after an upgrade incorporating optimized acquisition parameters and advanced real-time image processing algorithms. Dose area product (DAP) and radiation time of each digital fluoroscopy (DF), digital subtraction angiography (DSA) and cone beam CT (CBCT) were recorded. DSA image quality was assessed by two blinded and independent readers on a four-rank scale. Both cohorts showed no significant differences with regard to patient characteristics and tumour burden. The new system resulted in a statistically significant reduction of cumulative DAP of 66 % compared to the old platform (median 132.9 vs. 395.8 Gy cm{sup 2}). Individually, DAP of DF, DSA and CBCT decreased by 52 %, 79 % and 15 % (p < 0.01, p < 0.01, p = 0.51), respectively. No statistically significant differences in DSA image quality were found between the two imaging platforms. The new imaging platform significantly reduced radiation exposure for TACE procedures without increased radiation time or negative impact on DSA image quality. (orig.)

  13. Astragaloside Ⅳ reduces the expression level of P-glycoprotein in multidrug-resistant human hepatic cancer cell lines.

    Science.gov (United States)

    Wang, Pei-Pei; Xu, Du-Juan; Huang, Can; Wang, Wei-Ping; Xu, Wen-Ke

    2014-06-01

    Astragaloside is a saponin widely used in traditional Chinese medicine and has been reported to be a potent multidrug resistance (MDR) reversal agent. The present study investigated the role of astragaloside Ⅳ (ASIV) in the regulation of P-glycoprotein (P-gp, encoded by the mdr1 gene) and its effect on the reversal of MDR. The activity of ASIV was evaluated using human hepatic cancer cells Bel-7402 and the corresponding 5-fluorouracil (5-FU) resistant cells Bel-7402/FU. ASIV (0.08 mg/ml) potentiated the cytotoxicity of 5-FU which was demonstrated using the MTT assay on Bel-7402/FU cells. ASIV reduced the expression of P-gp as was revealed by immunocytochemistry. Accumulation and efflux studies with the P-gp substrate, rhodamine 123 (Rh123), demonstrated that ASIV inhibited P-gp-mediated drug efflux. Furthermore, it was demonstrated that ASⅣ enhanced the drug accumulation of 5-FU using a high performance liquid chromatography (HPLC) assay for drug resistant cells. Furthermore, ASIV may downregulate the expression of P-gp, which was examined using western blot analysis and polymerase chain reaction. In conclusion, the results of the present study indicated that ASIV reverses the drug resistance of Bel-7402/FU cells by downregulating the expression of mdr1. ASIV may represent a potent modulator of P-gp-mediated MDR in hepatic cancer therapy. PMID:24676670

  14. Robot-assisted surgery for kidney cancer increased access to a procedure that can reduce mortality and renal failure.

    Science.gov (United States)

    Chandra, Amitabh; Snider, Julia Thornton; Wu, Yanyu; Jena, Anupam; Goldman, Dana P

    2015-02-01

    Surgeons increasingly use robot-assisted minimally invasive surgery for a variety of medical conditions. For hospitals, the acquisition and maintenance of a robot requires a significant investment, but financial returns are not linked to any improvement in long-term patient outcomes in the current reimbursement environment. Kidney cancer provides a useful case study for evaluating the long-term value that this innovation can provide. Kidney cancer is generally treated through partial or radical nephrectomy, with evidence favoring the former procedure for appropriate patients. We found that robot-assisted surgery increased access to partial nephrectomy and that partial nephrectomy reduced mortality and renal failure. The value of the benefits of robot-assisted minimally invasive surgery to patients, in terms of quality-adjusted life-years gained, outweighed the health care and surgical costs to patients and payers by a ratio of five to one. In addition, we found no evidence that the availability of robot-assisted minimally invasive surgery increased the likelihood that inappropriate patients received partial nephrectomy. PMID:25646101

  15. 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.

  16. CURENT ADVANCES AND STRETEGIES FOR REDUCING THE SIDE EFFECTS OF RADIATION THERAPIES USED FOR VARIOUS TYPES OF CANCERS

    OpenAIRE

    Jagtar Singh; Manvi Kaur

    2013-01-01

    Cancer originates from the abnormal expression or activation of positive regulators and functional suppression of negative regulators. The World Health Organization (WHO) estimates that 84 million people will die of cancer between 2005 and 2015 without intervention. Research suggests that one-third of cancer deaths can be avoided through prevention. Major cancer treatment modalities are surgery, radiation therapy and chemotherapy. Radiation therapy is an important cancer treatment method and ...

  17. A1E reduces stemness and self-renewal in HPV 16-positive cervical cancer stem cells

    OpenAIRE

    Kwon, Taeho; Bak, Yesol; Ham, Sun-Young; Yu, Dae-Yeul; Yoon, Do-Young

    2016-01-01

    Background Cervical cancer is the second most common cancer in females. Recent reports have revealed the critical role of cervical cancer stem cells (CSCs) in tumorigenicity and metastasis. Previously we demonstrated that A1E exerts an anti-proliferative action, which inhibits the growth of cervical cancer cells. Methods A1E is composed of 11 oriental medicinal herbs. Cervical cancer cell culture, wund healing and invasion assay, flow cytometry, sheroid formation assay, and wstern blot assays...

  18. Using latent variables in logistic regression to reduce multicollinearity, A case-control example: breast cancer risk factors

    Directory of Open Access Journals (Sweden)

    Mohamad Amin Pourhoseingholi

    2008-03-01

    Full Text Available

    Background: Logistic regression is one of the most widely used models to analyze the relation between one or more explanatory variables and a categorical response in the field of epidemiology, health and medicine. When there is strong correlation among explanatory variables, i.e.multicollinearity, the efficiency of model reduces considerably. The objective of this research was to employ latent variables to reduce the effect of multicollinearity in analysis of a case-control study about breast cancer risk factors.

    Methods: The data belonged to a case-control study in which 300 women with breast cancer were compared to same number of controls. To assess the effect of multicollinearity, five highly correlated quantitative variables were selected. Ordinary logistic regression with collinear data was compared to two models contain latent variables were generated using either factor analysis or principal components analysis. Estimated standard errors of parameters were selected to compare the efficiency of models. We also conducted a simulation study in order to compare the efficiency of models with and without latent factors. All analyses were carried out using S-plus.

    Results: Logistic regression based on five primary variables showed an unusual odds ratios for age at first pregnancy (OR=67960, 95%CI: 10184-453503 and for total length of breast feeding (OR=0. On the other hand the parameters estimated for logistic regression on latent variables generated by both factor analysis and principal components analysis were statistically significant (P<0.003. Their standard errors were smaller than that of ordinary logistic regression on original variables. The simulation showed that in the case of normal error and 58% reliability the logistic regression based on latent variables is more efficient than that model for collinear variables.

    Conclusions: This research

  19. Inhibition of platelet activation prevents the P-selectin and integrin-dependent accumulation of cancer cell microparticles and reduces tumor growth and metastasis in vivo.

    Science.gov (United States)

    Mezouar, Soraya; Darbousset, Roxane; Dignat-George, Françoise; Panicot-Dubois, Laurence; Dubois, Christophe

    2015-01-15

    Venous thromboembolism constitutes one of the main causes of death during the progression of a cancer. We previously demonstrated that tissue factor (TF)-bearing cancer cell-derived microparticles accumulate at the site of injury in mice developing a pancreatic cancer. The presence of these microparticles at the site of thrombosis correlates with the size of the platelet-rich thrombus. The objective of this study was to determine the involvement of TF expressed by cancer cell-derived microparticles on thrombosis associated with cancer. We observed that pancreatic cancer cell derived microparticles expressed TF, its inhibitor tissue factor pathway inhibitor (TFPI) as well as the integrins αvβ1 and αvβ3. In mice bearing a tumor under-expressing TF, a significant decrease in circulating TF activity associated with an increase bleeding time and a 100-fold diminished fibrin generation and platelet accumulation at the site of injury were observed. This was mainly due to the interaction of circulating cancer cell-derived microparticles expressing TFPI with activated platelets and fibrinogen. In an ectopic model of cancer, treatment of mice with Clopidogrel, an anti-platelet drug, decreased the size of the tumors and restored hemostasis by preventing the accumulation of cancer cell-derived microparticles at the site of thrombosis. In a syngeneic orthotopic model of pancreatic cancer Clopidogrel also significantly inhibited the development of metastases. Together, these results indicate that an anti-platelet strategy may efficiently treat thrombosis associated with cancer and reduce the progression of pancreatic cancer in mice.

  20. A Transcriptome Post-Scaffolding Method for Assembling High Quality Contigs

    Directory of Open Access Journals (Sweden)

    Mingming Liu

    2014-01-01

    Full Text Available With the rapid development of high throughput sequencing technologies, new transcriptomes can be sequenced for little cost with high coverage. Sequence assembly approaches have been modified to meet the requirements for de novo transcriptomes, which have complications not found in traditional genome assemblies such as variation in coverage for each candidate mRNA and alternative splicing. As a consequence, de novo assembly strategies tend to generate a large number of redundant contigs due to sequence variations, which adversely affects downstream analysis and experiments. In this work we proposed TransPS, a transcriptome post-scaffolding method, to generate high quality, nonredundant de novo transcriptomes. TransPS shows promising results on the test transcriptome datasets, where redundancy is greatly reduced by more than 50% and, at the same time, coverage is improved considerably. The web server and source code are available.

  1. 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.

  2. Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models

    OpenAIRE

    Bianchi, Giovanna; Martella, Roberto; Ravera, Silvia; Marini, Cecilia; Capitanio, Selene; Orengo, Annamaria; Emionite, Laura; Lavarello, Chiara; Amaro, Adriana; Petretto, Andrea; Pfeffer, Ulrich; Sambuceti, Gianmario; Pistoia, Vito; Raffaghello, Lizzia; Longo, Valter D.

    2015-01-01

    Tumor chemoresistance is associated with high aerobic glycolysis rates and reduced oxidative phosphorylation, a phenomenon called “Warburg effect” whose reversal could impair the ability of a wide range of cancer cells to survive in the presence or absence of chemotherapy. In previous studies, Short-term-starvation (STS) was shown to protect normal cells and organs but to sensitize different cancer cell types to chemotherapy but the mechanisms responsible for these effects are poorly understo...

  3. 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

  4. An association between anti-platelet drug use and reduced cancer prevalence in diabetic patients: results from the Vermont Diabetes Information System Study

    Directory of Open Access Journals (Sweden)

    Ramos-Nino Maria E

    2010-06-01

    Full Text Available Abstract Background Diabetes is associated with an increased risk of several malignancies. Both diabetic patients and patients with cancer have an increase in platelet reactivity and platelet activation has recently emerged as a potential mediator of cancer progression. Drug therapies, such as aspirin, that reduce platelet reactivity reduce both cardiovascular and cancer risk. Methods We performed a cross-sectional analysis to assess the association between history of cancer and current anti-platelet drug use in a primary care population of adults with diabetes enrolled in the Vermont Diabetes Information System. Results Self-reported characteristics, medical history, and a complete medication list were recorded on 1007 diabetic adults. Fifty percent of diabetic patients used an anti-platelet drug. In unadjusted analysis, no association was seen between anti-platelet drug use and cancer history (OR = 0.93; P = .70. Platelet inhibitor use was associated with a decreased patient-reported history of malignancy in a multivariate logistic regression adjusted for age, sex, body mass index, comorbidity, and number of medications (OR = 0.66; CI 0.44-0.99; P = .045. Similar odds of association were seen in both males and females, and for aspirin and non-aspirin platelet inhibitor therapy. Conclusions Our data suggest an association between anti-platelet drug use and reduced cancer prevalence in patients with diabetes. Given the potentially large implications of our observations in the diabetic population, further studies are required to determine if this association is causal.

  5. Transcriptome and proteome profiling of colon mucosa from quercetin fed F344 rats point to tumor preventive mechanisms, increased mitochondrial fatty acid degradation and decreased glycolysis

    NARCIS (Netherlands)

    Dihal, A.A.; Woude, H. van der; Hendriksen, P.J.M.; Charif, H.; Dekker, L.J.; IJsselstijn, L.; Boer, V.C.J. de; Alink, G.M.; Burgers, P.C.; Rietjens, I.M.C.M.; Woutersen, R.A.; Stierum, R.H.

    2008-01-01

    Quercetin has been shown to act as an anticarcinogen in experimental colorectal cancer (CRC). The aim of the present study was to characterize transcriptome and proteome changes occurring in the distal colon mucosa of rats supplemented with 10 g quercetin/kg diet for 11 wk. Transcriptome data analyz

  6. Oomycete transcriptomics database: A resource for oomycete transcriptomes

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    Tripathy Sucheta

    2012-07-01

    Full Text Available Abstract Background Oomycete pathogens have attracted significant attention in recent years due to their economic impact. With improving sequencing technologies, large amounts of oomycete transcriptomics data are now available which have great biological utility. A known bottleneck with next generation sequencing data however lies with their analysis, interpretation, organization, storage and visualization. A number of efforts have been made in this respect resulting in development of a myriad of resources. Most of the existing NGS browsers work as standalone applications that need processed data to be uploaded to the browser locally for visualization. At the same time, several oomycete EST databases such as PFGD, ESTAP and SPC, are not available anymore, so there is an immediate need for a database resource that can store and disseminate this legacy information in addition to NGS data. Description Oomycetes Transcriptomics Database is an integrated transcriptome and EST data resource for oomycete pathogens. The database currently stores processed ABI SOLiD transcript sequences from Phytophthora sojae and its host soybean (P. sojae mycelia, healthy soybean and P. sojae-infected soybean as well as Illumina transcript sequences from five Hyaloperonospora arabidopsidis libraries. In addition to those resources, it has also a complete set of Sanger EST sequences from P. sojae, P. infestans and H. arabidopsidis grown under various conditions. A web-based transcriptome browser was created for visualization of assembled transcripts, their mapping to the reference genome, expression profiling and depth of read coverage for particular locations on the genome. The transcriptome browser merges EST-derived contigs with NGS-derived assembled transcripts on the fly and displays the consensus. OTD possesses strong query features and the database interacts with the VBI Microbial Database as well as the Phytophthora Transcriptomics Database. Conclusion Oomycete

  7. Bio reducible PEI-si RNA Nano complex for Liver Cancer Therapy: Transfection, Biodistribution, and Tumor Growth Inhibition In Vivo

    International Nuclear Information System (INIS)

    A bio reducible polyethylenimine (SS-PEI) was successfully applied as a non viral carrier for the delivery of plasmid DNA and VEGF-si RNA in vitro and in vivo. The SS-PEI could strongly condense DNA or si RNA into nano sized complexes (below 200 nm) with positive surface charges. In vitro transfection experiments using GFP plasmid as gene reporter showed that the complexes of SS-PEI/DNA were able to efficiently transfect HepG2 cells, with efficiency comparable to that of polyethylenimine, a gold standard for non viral gene delivery. Moreover, the complexes of SS-PEI/VEGF-si RNA could lead to reduced levels of VEGF protein in HepG2 cells in vitro. Treatment with the complexes of SS-PEI/VEGF-si RNA efficiently inhibited HepG2 tumor growth in an xenograft mouse model. The data of this study imply that the SS-PEI is a potent nucleic acid carrier applicable for liver cancer gene therapy.

  8. Targeting ID2 expression triggers a more differentiated phenotype and reduces aggressiveness in human salivary gland cancer cells.

    Science.gov (United States)

    Sumida, Tomoki; Ishikawa, Akiko; Nakano, Hiroyuki; Yamada, Tomohiro; Mori, Yoshihide; Desprez, Pierre-Yves

    2016-08-01

    Inhibitors of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We previously determined that ID1 was highly expressed in aggressive salivary gland cancer (SGC) cells in culture. Here, we show that ID2 is also expressed in aggressive SGC cells. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. Moreover, ID2 knockdown almost completely suppresses invasion and the expression of matrix metalloproteinase 9. In conclusion, ID2 expression maintains an aggressive phenotype in SGC cells, and ID2 repression triggers a reduction in cell aggressiveness. ID2 therefore represents a potential therapeutic target during SGC progression. ID proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. ID2 therefore represents a potential therapeutic target during SGC progression. PMID:27364596

  9. 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

  10. TGF-β Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia

    OpenAIRE

    Stephanie H Greco; Lena Tomkötter; Anne-Kristin Vahle; Rae Rokosh; Antonina Avanzi; Syed Kashif Mahmood; Michael Deutsch; Sara Alothman; Dalia Alqunaibit; Atsuo Ochi; Constantinos Zambirinis; Tasnima Mohaimin; Mauricio Rendon; Elliot Levie; Mridul Pansari

    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 s...

  11. The effectiveness of hypnosis in reducing pain and suffering among women with metastatic breast cancer and among women with temporomandibular disorder.

    Science.gov (United States)

    Nash, Michael R; Tasso, Anthony

    2010-10-01

    The authors describe two studies of special interest to clinicians and clinical researchers. Both are randomized controlled studies, exclusively focused on female patients. The first study tests whether a year-long weekly group intervention including hypnosis can reduce cancer pain among women with metastatic breast cancer. Findings suggest the intervention slowed the increase in reported pain over a 12-month period relative to controls. The second study examines the effect of hypnosis in women suffering from temporomandibular disorder (TMD), with a special focus on function as well as pain. Hypnosis reduced TMD pain as measured by a numerical-rating scale. PMID:20799126

  12. Effectiveness and feasibility of using the computerized interactive virtual space in reducing depressive symptoms of Hong Kong Chinese children hospitalized with cancer.

    Science.gov (United States)

    Li, William H C; Chung, Joyce O K; Ho, Eva K Y; Chiu, Sau Ying

    2011-07-01

    PURPOSE. To examine the effectiveness and feasibility of using the computerized interactive virtual space in reducing depressive symptoms of children hospitalized with cancer. DESIGN AND METHODS. A nonequivalent control group design was employed. Children (8-16 years of age; n= 122) admitted to a pediatric oncology ward during a 14-month period were recruited. RESULTS. The results support the effectiveness and feasibility of using the computerized interactive virtual space in reducing depressive symptoms of children hospitalized with cancer. PRACTICE IMPLICATIONS. The results heighten the awareness in nurses of the importance of integrating play activities as an essential component of holistic and quality nursing care.

  13. Highly efficient nuclear delivery of anti-cancer drugs using a bio-functionalized reduced graphene oxide.

    Science.gov (United States)

    Zheng, Xin Ting; Ma, Xiao Qing; Li, Chang Ming

    2016-04-01

    Targeted drug delivery has become important, attractive and challenging in biomedical science and applications. Anti-HER2 antibody-conjugated poly-l-lysine functionalized reduced graphene oxide (anti-HER2-rGO-PLL) nanocarriers were prepared to efficiently deliver doxorubicin targeting at the nucleus of HER2 over-expressing cancer cells. The polycationic PLL was first covalently grafted to graphene oxide (GO) nanosheets followed by reduction to obtain rGO-PLL with high drug loading and good colloidal stability. The anti-HER2 antibodies were subsequently conjugated to the amino groups of PLL to achieve excellent cell uptake capability. Cellular uptake of anti-HER2-rGO-PLL into MCF7/HER2 cells is significantly higher than that of rGO-PLL due to the specific targeting of anti-HER2 to HER2 overexpressing breast cancer cells. Additionally the anti-HER2-rGO-PLL enables a fast accumulation of DOX inside the nucleus, its subcellular site of action. In vitro cytotoxicity measurements clearly reveal a seven fold improvement in the anticancer efficacy for anti-HER2-rGO-PLL/DOX in comparison to rGO-PLL/DOX. The enhanced anticancer efficacy could be ascribed to the different intracellular DOX distributions resulted from the different internalization routes that are energy-dependent macropinocytosis and energy-independent direct penetration by anti-HER2-rGO-PLL and rGO-PLL, respectively. The results demonstrate that anti-HER2 conjugated rGO-PLL developed is a promising vehicle for efficient nuclear delivery of chemotherapeutic agents to HER2 over-expressing tumours. PMID:26773607

  14. Taurolidine-citrate lock solution (TauroLock significantly reduces CVAD-associated grampositive infections in pediatric cancer patients

    Directory of Open Access Journals (Sweden)

    Fleischhack Gudrun

    2008-07-01

    Full Text Available Abstract Background Taurolidin/Citrate (TauroLock™, a lock solution with broad spectrum antimicrobial activity, may prevent bloodstream infection (BSI due to coagulase-negative staphylococci (CoNS or 'MRSE' in case of methicillin-resistant isolates in pediatric cancer patients with a long term central venous access device (CVAD, Port- or/Broviac-/Hickman-catheter type. Methods In a single center prospective 48-months cohort study we compared all patients receiving anticancer chemotherapy from April 2003 to March 2005 (group 1, heparin lock with 200 IU/ml sterile normal saline 0.9%; Canusal® Wockhardt UK Ltd, Wrexham, Wales and all patients from April 2005 to March 2007 (group 2; taurolidine 1.35%/Sodium Citrate 4%; TauroLock™, Tauropharm, Waldbüttelbrunn, Germany. Results In group 1 (heparin, 90 patients had 98 CVAD in use during the surveillance period. 14 of 30 (47% BSI were 'primary Gram positive BSI due to CoNS (n = 4 or MRSE (n = 10' [incidence density (ID; 2.30 per 1000 inpatient CVAD-utilization days]. In group 2 (TauroLock™, 89 patients had 95 CVAD in use during the surveillance period. 3 of 25 (12% BSI were caused by CoNS. (ID, 0.45. The difference in the ID between the two groups was statistically significant (P = 0.004. Conclusion The use of Taurolidin/Citrate (TauroLock™ significantly reduced the number and incidence density of primary catheter-associated BSI due to CoNS and MRSE in pediatric cancer patients.

  15. Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time.

    Science.gov (United States)

    Shabo, Ivan; Olsson, Hans; Sun, Xiao-Feng; Svanvik, Joar

    2009-10-15

    Expression of the macrophage antigen CD163 in breast cancer cells is recently shown to be related to early distant recurrence and shortened survival. In this study, 163 patients with rectal cancer, included in the Swedish rectal cancer trial and followed up for a median of 71 months, were examined for the expression of CD163 in the primary tumors. The cancer cells expressed CD163 in the primary tumors in 23% (n = 32) of the patients. In pretreatment biopsies from 101 patients, 10 had CD163-positive cancers and these patients had earlier local recurrence (p CD163-negative tumors. When studying surgical specimens from 61 patients randomized to preoperative irradiation (5 x 5 Gy delivered in 1 week), it was found that 31% were CD163 positive whereas the corresponding figure was only 17% for 78 patients who were nonirradiated (p CD163-positive tumors there was a reduced apoptotic activity as measured with the Termina deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique (p = 0.018). There tended also to be an increased proliferation activity measured as an expression of Ki-67 non significant (NS). It is concluded that primary rectal cancers may express CD-163, and this phenotypic macrophage trait is related to early local recurrence, shorter survival time and reduced apoptosis. Furthermore, the expression of CD163 is more common after irradiation. PMID:19582880

  16. RNA Editing Dynamically Rewrites the Cancer Code

    Science.gov (United States)

    Rayon-Estrada, Violeta; Papavasiliou, F. Nina; Harjanto, Dewi

    2016-01-01

    Global analyses of cancer transcriptomes demonstrate that ADAR (adenosine deaminase, RNA-specific)-mediated RNA editing dynamically contributes to genetic alterations in cancer, and directly correlates with progression and prognosis. RNA editing is abundant and frequently elevated in cancer, and affects functionally and clinically relevant sites in both coding and non-coding regions of the transcriptome. Therefore, ADAR and differentially edited transcripts may be promising biomarkers or targets for therapy.

  17. Calpain Inhibitor Reduces Cancer-induced Bone Pain Possibly Through Inhibition of Osteoclastogenesis in Rat Cancer-induced Bone Pain Model

    Institute of Scientific and Technical Information of China (English)

    Jia-Ying Xu; Yu Jiang; Wei Liu; Yu-Guang Huang

    2015-01-01

    Background:Calpain,a calcium-dependent cysteine protease,has been demonstrated to regulate osteoclastogenesis,which is considered one of the major reasons for cancer-induced bone pain (CIBP).In the present study,calpain inhibitor was applied in a rat CIBP model to determine whether it could reduce CIBP through regulation of osteoclastogenesis activity.Methods:A rat CIBP model was established with intratibial injection of Walker 256 cells.Then,the efficacy of intraperitoneal administered calpain inhibitor Ⅲ (MDL28170,1 mg/kg) on mechanical withdrawal threshold (MWT) of bilateral hind paws was examined on postoperative days (PODs) 2,5,8,11,and 14.On POD 14,the calpain inhibitor's effect on tumor bone tartrate-resistant acid phosphatase (TRAP) stain and radiology was also carefully investigated.Results:Pain behavioral tests in rats showed that the calpain inhibitor effectively attenuated MWTs of both the surgical side and contralateral side hind paws on POD 5,8,and 11 (P < 0.05).TRAP-positive cell count of the surgical side bone was significantly decreased in the calpain inhibitor group compared with the vehicle group (P < 0.05).However,bone resorption and destruction measured by radiographs showed no difference between the two groups.Conclusions:Calpain inhibitor can effectively reduce CIBP of both the surgical side and nonsurgical side after tumor injection in a rat CIBP model.It may be due to the inhibition of receptor activator of nuclear factor-kappa B ligand-induced osteoclastogenesis.Whether a calpain inhibitor could be a novel therapeutic target to treat CIBP needs further investigation.

  18. STI571 reduces TRAIL-induced apoptosis in colon cancer cells: c-Abl activation by the death receptor leads to stress kinase-dependent cell death

    Directory of Open Access Journals (Sweden)

    Huang Duen-Yi

    2012-03-01

    Full Text Available Abstract Background In an effort to achieve better cancer therapies, we elucidated the combination cancer therapy of STI571 (an inhibitor of Bcr-Abl and clinically used for chronic myelogenous leukemia and TNF-related apoptosis-inducing ligand (TRAIL, a developing antitumor agent in leukemia, colon, and prostate cancer cells. Methods Colon cancer (HCT116, SW480, prostate cancer (PC3, LNCaP and leukemia (K562 cells were treated with STI571 and TRAIL. Cell viability was determined by MTT assay and sub-G1 appearance. Protein expression and kinase phosphorylation were determined by Western blotting. c-Abl and p73 activities were inhibited by target-specific small interfering (siRNA. In vitro kinase assay of c-Abl was conducted using CRK as a substrate. Results We found that STI571 exerts opposite effects on the antitumor activity of TRAIL. It enhanced cytotoxicity in TRAIL-treated K562 leukemia cells and reduced TRAIL-induced apoptosis in HCT116 and SW480 colon cancer cells, while having no effect on PC3 and LNCaP cells. In colon and prostate cancer cells, TRAIL caused c-Abl cleavage to the active form via a caspase pathway. Interestingly, JNK and p38 MAPK inhibitors effectively blocked TRAIL-induced toxicity in the colon, but not in prostate cancer cells. Next, we found that STI571 could attenuate TRAIL-induced c-Abl, JNK and p38 activation in HCT116 cells. In addition, siRNA targeting knockdown of c-Abl and p73 also reduced TRAIL-induced cytotoxicity, rendering HCT116 cells less responsive to stress kinase activation, and masking the cytoprotective effect of STI571. Conclusions All together we demonstrate a novel mediator role of p73 in activating the stress kinases p38 and JNK in the classical apoptotic pathway of TRAIL. TRAIL via caspase-dependent action can sequentially activate c-Abl, p73, and stress kinases, which contribute to apoptosis in colon cancer cells. Through the inhibition of c-Abl-mediated apoptotic p73 signaling, STI571 reduces

  19. Thrombomodulin reduces tumorigenic and metastatic potential of lung cancer cells by up-regulation of E-cadherin and down-regulation of N-cadherin expression.

    Science.gov (United States)

    Zheng, Nana; Huo, Zihe; Zhang, Bin; Meng, Mei; Cao, Zhifei; Wang, Zhiwei; Zhou, Quansheng

    2016-08-01

    Thrombomodulin (TM) is an endothelial cell membrane protein and plays critical roles in anti-thrombosis, anti-inflammation, vascular endothelial protection, and is traditionally regarded as a "vascular protection god". In recent years, although TM has been reported to be down-regulated in a variety of malignant tumors including lung cancer, the role and mechanism of TM in lung cancer are enigmatic. In this study, we found that induction of TM overexpression by cholesterol-reducing drug atorvastatin significantly diminished the tumorigenic capability of the lung cancer cells. Moreover, we demonstrated that TM overexpression caused G0/G1 phase arrest and markedly reduced the colony forming capability of the cells. Furthermore, overexpression of TM inhibited cell migration and invasion. Consistently, depletion of TM promoted cell growth, reduced the cell population at the G0/G1 phase, and enhanced cell migratory ability. Mechanistic study revealed that TM up-regulated E-cadherin but down-regulated N-cadherin expression, resulting in reversal of epithelial-mesenchymal transition (EMT) in the lung cancer cells. Moreover, silencing TM expression led to decreased E-cadherin and increased N-cadherin. Taken together, our study suggests that TM functions as a tumor suppressive protein, providing a conceptual framework for inducing TM overexpression as a sensible strategy and approach for novel anti-lung cancer drug discovery. PMID:27223053

  20. Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    M. Olivan

    2015-01-01

    Full Text Available 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.

  1. Small RNA transcriptome investigation based on next-generation sequencing technology

    Institute of Scientific and Technical Information of China (English)

    Linglin Zhou; Xueying Li; Qi Liu; Fangqing Zhao; Jinyu Wu

    2011-01-01

    Over the past decade,there has been a growing realization that studying the small RNA transcriptome is essential for understanding the complexity of transcriptional regulation.With an increased throughput and a reduced cost,next-generation sequencing technology has provided an unprecedented opportunity to measure the extent and complexity of small RNA transcriptome.Meanwhile,the large amount of obtained data and varied technology platforms have also posed multiple challenges for effective data analysis and mining.To provide some insight into the small RNA transcriptome investigation,this review describes the major small RNA classes,experimental methods to identify small RNAs,and available bioinformatics tools and databases.

  2. Combination treatment with flavonoid morin and telomerase inhibitor MST‑312 reduces cancer stem cell traits by targeting STAT3 and telomerase.

    Science.gov (United States)

    Chung, Seyung S; Oliva, Bryant; Dwabe, Sami; Vadgama, Jaydutt V

    2016-08-01

    Colorectal cancer (CRC) is one of the most commonly diagnosed cancers worldwide. The malignant CRC that undergoes metastasis in the advanced stage is usually refractory to existing chemotherapy and shows a poor prognosis. However, to date, efficient targeted-therapy for metastatic CRC is ill-defined. We tested the hypothesis that combined treatment of flavonoid morin and telomerase inhibitor MST‑312 may reduce the cancer stem cell (CSC) traits. To characterize CSC phenotype, we performed the CD133/CD44 subpopulation profiling, tumorsphere formation assay, cell invasion assay and wound healing assay. We have examined the augmenting effects of the combined treatment of morin and MST‑312 for 5-FU (5-fluorouracil) efficacy in human colorectal cancer. Morin and MST‑312 combined treatment reduced CD133 (+) and CD44 (+) subpopulations in human colorectal and breast cancer cells, respectively. Tumorsphere formation and cell invasiveness were decreased with the morin and MST‑312 combination treatment. Consistent with these data, morin and MST‑312 treatment decreased the wound healing capacity of human breast cancer cells. Stress and apoptosis antibody arrays revealed that there were specific upregulated and downregulated proteins resulting from different treatments. Phosphorylation levels of BAD, p53 and Chk1 were enhanced upon morin/MST‑312 treatments in HT-29 cells, whereas caspase-3 cleavage level and expression of IκBα were downregulated by combined morin/MST‑312 treatment in SW620 cells. Finally, morin and MST‑312 co-treatment further augmented the 5-FU efficacy, chemosensitizing the 5-FU resistant human colorectal cancer cells. Taken together, our study suggests that novel targeted-therapy can be implemented by using flavonoid morin and telomerase inhibitor MST‑312 for improved cancer prognosis. PMID:27279256

  3. Prospective study found thatperipheral lymph node sampling reduced the false-negative rate ofsentinel lymph node biopsy forbreast cancer

    Institute of Scientific and Technical Information of China (English)

    ChaoHan; BenYang; WenShuZuo; YanSongLiu; GangZheng; LiYang; MeiZhuZheng

    2016-01-01

    Background:Although sentinel lymph node biopsy (SLNB) can accurately predict the status of axillary lymph node (ALN) metastasis, the high false‑negative rate (FNR) of SLNB is still the main obstacle for the treatment of patients who receive SLNB instead of ALN dissection (ALND). The purpose of this study was to evaluate the clinical signiifcance of SLNB combined with peripheral lymph node (PLN) sampling for reducing the FNR for breast cancer and to discuss the effect of “skip metastasis” on the FNR of SLNB. Methods:At Shandong Cancer Hospital Affliated to Shandong University between March 1, 2012 and June 30, 2015, the sentinel lymph nodes (SLNs) of 596 patients with breast cancer were examined using radiocolloids with blue dye tracer. First, the SLNs were removed; then, the area surrounding the original SLNs was selected, and the visible lymph nodes in a ifeld of 3–5cm in diameter around the center (i.e., PLNs) were removed, avoiding damage to the structure of the breast. Finally, ALND was performed. The SLNs, PLNs, and remaining ALNs underwent pathologic examination, and the relationship between them was analyzed. Results:The identiifcation rate of SLNs in the 596 patients was 95.1% (567/596); the metastasis rate of ALNs was 33.7% (191/567); the FNR of pure SLNB was 9.9% (19/191); and after the SLNs and PLNs were eliminated, the FNR was 4.2% (8/191), which was signiifcantly decreased compared with the FNR before removal of PLNs (P=0.028). According to the detected number (N) of SLNs, the patients were divided into four groups of N=1, 2, 3, and≥4; the FNR in these groups was 19.6, 9.8, 7.3, and 2.3%, respectively. For the patients with≤2 or≤3 detected SLNs, the FNR after removal of PLNs was signiifcantly decreased compared with that before removal of PLNs (N≤2: 14.0% vs. 4.7%, P=0.019; N≤3: 12.2% vs. 4.7%,P=0.021), whereas for patients with≥4 detected SLNs, the decrease in FNR was not statistically signiifcant (P=1.000). In the entire cohorts

  4. Stearidonic acid-enriched flax oil reduces the growth of human breast cancer in vitro and in vivo.

    Science.gov (United States)

    Subedi, K; Yu, H-M; Newell, M; Weselake, R J; Meesapyodsuk, D; Qiu, X; Shah, S; Field, C J

    2015-01-01

    The 20 and 22 carbon n-3 long-chain polyunsaturated fatty acids (LCPUFA) inhibit the growth of tumors in vitro and in animal models, but less is known about the 18 carbon n-3, stearidonic acid (SDA). This study aimed to establish and determine a mechanism for the anti-cancer activity of SDA-enriched oil (SO). SO (26 % of lipid) was produced by genetically engineering flax and used to treat human tumorigenic (MDA-MB-231, MCF-7) and non-tumorigenic (MCF-12A) breast cells. Nu/nu mice bearing MDA-MB-231 tumor were fed SO (SDA, 4 % of fat). Cell/tumor growth, phospholipid (PL) composition, apoptosis, CD95, and pro-apoptotic molecules were determined in SO-treated cells/tumors. Compared to a control lipid mixture, SO reduced (p < 0.05) the number of tumorigenic, but not MCF-12A cells, and resulted in higher concentration of most of the n-3 fatty acids in PL of all cells (p < 0.05). However, docosapentaenoic acid increased only in tumorigenic cells (p < 0.05). SO diet decreased tumor growth and resulted in more n-3 LCPUFA, including DPA and less arachidonic acid (AA) levels in major tumor PL (p < 0.05). Treatment of MDA-MB-231 cells/tumors with SO resulted in more apoptotic cells (in tumors) and in vivo and in vitro, more CD95+ positive cells and a higher expression of apoptotic molecules caspase-10, Bad, or Bid (p < 0.05). Supplementing SO alters total PL and PL classes by increasing membrane content of n-3 LCPUFA and lowering AA (in vivo), which is associated with increased CD95-mediated apoptosis, thereby suggesting a possible mechanism for reduce tumor survival. PMID:25417173

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

    OpenAIRE

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

    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 path...

  6. The REDUCE metagram: a comprehensive prediction tool for determining the utility of dutasteride chemoprevention in men at risk for prostate cancer

    OpenAIRE

    Carvell eNguyen; Brandon eIsariyawongse; Changhong eYu; Michael eKattan

    2012-01-01

    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 bio...

  7. The REDUCE metagram: a comprehensive prediction tool for determining the utility of dutasteride chemoprevention in men at risk for prostate cancer

    OpenAIRE

    Nguyen, Carvell T.; Isariyawongse, Brandon; Yu, Changhong; Michael W Kattan

    2012-01-01

    Introduction: 5-alpha reductase inhibitors can reduce the risk of prostate cancer (PCa) 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 9 endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biop...

  8. Orally available selective melanocortin-4 receptor antagonists stimulate food intake and reduce cancer-induced cachexia in mice.

    Directory of Open Access Journals (Sweden)

    Philipp Weyermann

    Full Text Available BACKGROUND: Cachexia is among the most debilitating and life-threatening aspects of cancer. It represents a metabolic syndrome affecting essential functional circuits involved in the regulation of homeostasis, and includes anorexia, fat and muscle tissue wasting. The anorexigenic peptide alpha-MSH is believed to be crucially involved in the normal and pathologic regulation of food intake. It was speculated that blockade of its central physiological target, the melanocortin (MC-4 receptor, might provide a promising anti-cachexia treatment strategy. This idea is supported by the fact that in animal studies, agouti-related protein (AgRP, the endogenous inverse agonist at the MC-4 receptor, was found to affect two hallmark features of cachexia, i.e. to increase food intake and to reduce energy expenditure. METHODOLOGY/PRINCIPAL FINDINGS: SNT207707 and SNT209858 are two recently discovered, non peptidic, chemically unrelated, orally active MC-4 receptor antagonists penetrating the blood brain barrier. Both compounds were found to distinctly increase food intake in healthy mice. Moreover, in mice subcutaneously implanted with C26 adenocarcinoma cells, repeated oral administration (starting the day after tumor implantation of each of the two compounds almost completely prevented tumor induced weight loss, and diminished loss of lean body mass and fat mass. CONCLUSIONS/SIGNIFICANCE: In contrast to the previously reported peptidic and small molecule MC-4 antagonists, the compounds described here work by the oral administration route. Orally active compounds might offer a considerable advantage for the treatment of cachexia patients.

  9. [Application of photodynamic therapy to reduce the amount of resection for non-small cell lung cancer].

    Science.gov (United States)

    Akopov, A L; Rusanov, A A; Chistiakov, I V; Urtenova, M A; Kazakov, N V; Gerasin, A V; Papaian, G V

    2013-01-01

    A prospective analysis of results of combined treatment of 22 patients with central stage II-III non-small cell lung cancer (NSCLC) was performed (the defeat of the main bronchi or lower parts of the trachea), which initially had been regarded as unresectable or inoperable (12 patients for functional reasons could not pass pneumonectomy, and in 10 patients a contraindication to primary surgery was the involvement of the distal trachea in tumor), but underwent surgery after preoperative treatment.Combination therapy included preoperative endobronchial photodynamic therapy (PDT) and chemotherapy followed by surgery and intraoperative PDT resection margins. PDT was carried out with the use of chlorine E6 (Radachlorin) and light wavelength of 662 nm. Overall response rate after neoadjuvant treatment was 82 %, endoscopic remission was observed in 21 of 22 patients (95%). 10 patients underwent pneumonectomy, 12--lobectomy. 19 surgical interventions were regarded as radical (R0--86%), 3--as microscopically non-radical (R1--14%). Degree of lymphatic metastasis spreading pN0 was detected in 6 patients (27 %), pN1--in 14 (64%) and pN2--in 2 patients (9%). Surgical lethality was 5%. In the late time of the whole observation period none of the patients developed local recurrence. One-year survival was 95%, 3-year--91%. PDT can play an important role in combination with surgical treatment for NSCLC and reduces the amount of resection in part of initially unresectable or inoperable patients. PMID:24624784

  10. 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. PMID:27217837

  11. Flurbiprofen axetil reduces postoperative sufentanil consumption and enhances postoperative analgesic effects in patients with colorectal cancer surgery.

    Science.gov (United States)

    Lin, Xue; Zhang, Ruiqin; Xing, Jingchun; Gao, Xiaocui; Chang, Pan; Li, Wenzhi

    2014-01-01

    To investigate the effects of different strategies of flurbiprofen axetil (FA) administration on postoperative pain and sufentanil (SF) consumption after open colorectal cancer (CRC) surgery. Forty patients undergoing elective CRC resection were divided into two groups (n = 20 each). Patients in the F50+50 group received 50 mg of intravenous FA 30 min before skin incision and six hours after the first dose; patients in the F100 group received 100 mg of intravenous FA 30 min before skin incision. Perioperative plasma FA (CFA) and SF concentrations (CSF) were determined. Analgesic and sedative efficacy were evaluated using the visual analogue scale (VAS), Bruggman Comfort Scale (BCS), and Ramsay sedation scale. The time to the first PCIA trigger, the number of patients that pressed the PCIA trigger within 24 h after surgery, and the cumulative doses of SF consumption within 6 and 24 h after surgery were recorded. At postoperative 6 and 24 h, CFA was significantly higher, CSF was significantly lower, and the number of patients that pressed the PCIA trigger and the consumption of SF were significantly lower in the F50+50 group compared with the F100 group. At postoperative 4 h, VAS and BCS were significantly lower in the F50+50 group compared with the F100 group (P < 0.05). An administration strategy that maintains a relatively high plasma FA concentration at 6-24 h post-operatively may reduce postoperative inflammatory pain and SF-requirement in patients undergoing CRC resection.

  12. ENERGY-DEPENDENT PROCESSES INVOLVED IN REDUCED DRUG ACCUMULATION IN MULTIDRUG-RESISTANT HUMAN LUNG-CANCER CELL-LINES WITHOUT P-GLYCOPROTEIN EXPRESSION

    NARCIS (Netherlands)

    VERSANTVOORT, CHM; BROXTERMAN, HJ; PINEDO, HM; DEVRIES, EGE; FELLER, N; KUIPER, CM; LANKELMA, J

    1992-01-01

    Mechanisms contributing to reduced cytotoxic drug accumulation were studied in two multidrug-resistant (MDR) human lung cancer cell lines without P-glycoprotein expression. In these (non-small cell) SW-1573/ 2R120 and (small cell) GLC4/ADR MDR cells, the steady-state accumulation of [C-14]daunorubic

  13. To Screen or not to Screen: Low Dose Computed Tomography in Comparison to Chest Radiography or Usual Care in Reducing Morbidity and Mortality from Lung Cancer

    Science.gov (United States)

    Kamdar, Jay; Moats, Austin; Nguyen, Brenda

    2016-01-01

    Lung cancer has the highest mortality rate of all cancers. This paper seeks to address the question: Can the mortality of lung cancer be decreased by screening with low-dose computerized tomography (LDCT) in higher risk patients compared to chest X-rays (CXR) or regular patient care? Currently, CXR screening is recommended for certain high-risk patients. Several recent trials have examined the effectiveness of LDCT versus chest radiography or usual care as a control. These trials include National Lung Screening Trial (NLST), Detection And screening of early lung cancer with Novel imaging TEchnology (DANTE), Lung Screening Study (LSS), Depiscan, Italian Lung (ITALUNG), and Dutch-Belgian Randomized Lung Cancer Screening Trial (Dutch acronym: NELSON study). NLST, the largest trial (n=53, 454), demonstrated a decrease in mortality from lung cancer in the LDCT group (RRR=20%, P=0.004). LSS demonstrated a greater sensitivity in detecting both early stage and any stage of lung cancer in comparison to traditional CXR. Although the DANTE trial yielded data consistent with findings in LSS, it also showed that via LDCT screening a greater proportion of patients were placed under unnecessary surgical procedures. The Depiscan trial yielded a high nodule detection rate at the cost of a high false-positive rate compared to CXR screening. The ITALUNG and NELSON trials demonstrated the early detection capabilities of LDCT for lung cancers compared to usual care without surveillance imaging. False-positive findings with unnecessary workup, intervention, and radiation exposure remain significant concerns for routine LDCT screening. However, current data suggests LDCT may provide a highly sensitive and specific means for detecting lung cancers and reducing mortality. PMID:27375974

  14. To Screen or not to Screen: Low Dose Computed Tomography in Comparison to Chest Radiography or Usual Care in Reducing Morbidity and Mortality from Lung Cancer.

    Science.gov (United States)

    Dajac, Joshua; Kamdar, Jay; Moats, Austin; Nguyen, Brenda

    2016-01-01

    Lung cancer has the highest mortality rate of all cancers. This paper seeks to address the question: Can the mortality of lung cancer be decreased by screening with low-dose computerized tomography (LDCT) in higher risk patients compared to chest X-rays (CXR) or regular patient care? Currently, CXR screening is recommended for certain high-risk patients. Several recent trials have examined the effectiveness of LDCT versus chest radiography or usual care as a control. These trials include National Lung Screening Trial (NLST), Detection And screening of early lung cancer with Novel imaging TEchnology (DANTE), Lung Screening Study (LSS), Depiscan, Italian Lung (ITALUNG), and Dutch-Belgian Randomized Lung Cancer Screening Trial (Dutch acronym: NELSON study). NLST, the largest trial (n=53, 454), demonstrated a decrease in mortality from lung cancer in the LDCT group (RRR=20%, P=0.004). LSS demonstrated a greater sensitivity in detecting both early stage and any stage of lung cancer in comparison to traditional CXR. Although the DANTE trial yielded data consistent with findings in LSS, it also showed that via LDCT screening a greater proportion of patients were placed under unnecessary surgical procedures. The Depiscan trial yielded a high nodule detection rate at the cost of a high false-positive rate compared to CXR screening. The ITALUNG and NELSON trials demonstrated the early detection capabilities of LDCT for lung cancers compared to usual care without surveillance imaging. False-positive findings with unnecessary workup, intervention, and radiation exposure remain significant concerns for routine LDCT screening. However, current data suggests LDCT may provide a highly sensitive and specific means for detecting lung cancers and reducing mortality. PMID:27375974

  15. Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain

    OpenAIRE

    Ruirui Pan; Huiting Di; Jinming Zhang; Zhangxiang Huang; Yuming Sun; Weifeng Yu; Feixiang Wu

    2015-01-01

    Although bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4) plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the downregulation of TLR4 by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for bone cancer ...

  16. 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

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

    International Nuclear Information System (INIS)

    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

  18. 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)

    L.L. Kodach; R.J. Jacobs; P.W. Voorneveld; M.E. Wildenberg; H.W. Verspaget; T. van Wezel; H. Morreau; D.W. Hommes; M.P. Peppelenbosch; G.R. van den Brink; J.C.H. Hardwick

    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 cance

  19. 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.

  20. Binding and inhibition of drug transport proteins by heparin: a potential drug transporter modulator capable of reducing multidrug resistance in human cancer cells.

    Science.gov (United States)

    Chen, Yunliang; Scully, Michael; Petralia, Gloria; Kakkar, Ajay

    2014-01-01

    A major problem in cancer treatment is the development of resistance to chemotherapeutic agents, multidrug resistance (MDR), associated with increased activity of transmembrane drug transporter proteins which impair cytotoxic treatment by rapidly removing the drugs from the targeted cells. Previously, it has been shown that heparin treatment of cancer patients undergoing chemotherapy increases survival. In order to determine whether heparin is capable reducing MDR and increasing the potency of chemotherapeutic drugs, the cytoxicity of a number of agents toward four cancer cell lines (a human enriched breast cancer stem cell line, two human breast cancer cell lines, MCF-7 and MDA-MB-231, and a human lung cancer cell line A549) was tested in the presence or absence of heparin. Results demonstrated that heparin increased the cytotoxicity of a range of chemotherapeutic agents. This effect was associated with the ability of heparin to bind to several of the drug transport proteins of the ABC and non ABC transporter systems. Among the ABC system, heparin treatment caused significant inhibition of the ATPase activity of ABCG2 and ABCC1, and of the efflux function observed as enhanced intracellular accumulation of specific substrates. Doxorubicin cytoxicity, which was enhanced by heparin treatment of MCF-7 cells, was found to be under the control of one of the major non-ABC transporter proteins, lung resistance protein (LRP). LRP was also shown to be a heparin-binding protein. These findings indicate that heparin has a potential role in the clinic as a drug transporter modulator to reduce multidrug resistance in cancer patients. PMID:24253450

  1. CURENT ADVANCES AND STRETEGIES FOR REDUCING THE SIDE EFFECTS OF RADIATION THERAPIES USED FOR VARIOUS TYPES OF CANCERS

    Directory of Open Access Journals (Sweden)

    Jagtar Singh

    2013-03-01

    Full Text Available Cancer originates from the abnormal expression or activation of positive regulators and functional suppression of negative regulators. The World Health Organization (WHO estimates that 84 million people will die of cancer between 2005 and 2015 without intervention. Research suggests that one-third of cancer deaths can be avoided through prevention. Major cancer treatment modalities are surgery, radiation therapy and chemotherapy. Radiation therapy is an important cancer treatment method and is used for approximately 50% of all cancer patients with varying success. Therapy uses high-energy waves or particles to destroy cancer cells. It can be used basically for three main reasons: to achieve high radiation dose into tumors; minimizing dose into surrounding normal tissues; to avoid complications as far as possible. The recent advances in this treatment method have led to the improvement in cancer death statistics. It can also be combined with surgery or chemotherapy for better results. This review covers general applications, various side effects/agents and factors affecting to get rid of these effects and strategies to improve radiation therapy.

  2. 5-azacytidine induces anoikis, inhibits mammosphere formation and reduces metalloproteinase 9 activity in MCF-7 human breast cancer cells.

    Science.gov (United States)

    Chang, Hsueh-Wei; Wang, Hui-Chun; Chen, Chiau-Yi; Hung, Ting-Wei; Hou, Ming-Feng; Yuan, Shyng-Shiou F; Huang, Chih-Jen; Tseng, Chao-Neng

    2014-01-01

    Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported to be resilient to common chemotherapeutic drugs in comparison to regular cancer cells, screening for compounds selectively targeting cancer stem cells may provide an effective therapeutic strategy. We found that 5-azacytidine (5-AzaC) selectively induced anoikis of MCF-7 in suspension cultures with an EC₅₀ of 8.014 µM, and effectively inhibited tumorsphere formation, as well as the migration and matrix metalloproteinases-9 (MMP-9) activity of MCF-7 cells. Furthermore, 5-AzaC and radiation collaboratively inhibited MCF-7 tumorsphere formation at clinically relevant radiation doses. Investigating the underlying mechanism may provide insight into signaling pathways crucial for cancer stem cell survival and pave the way to novel potential therapeutic targets. PMID:24633350

  3. Targeting of miR9/NOTCH1 interaction reduces metastatic behavior in triple-negative breast cancer.

    Science.gov (United States)

    Mohammadi-Yeganeh, Samira; Mansouri, Ardalan; Paryan, Mahdi

    2015-11-01

    Many reports have indicated deregulation of a variety of microRNAs (miRNAs) in human cancers. In this study, we appraised miR-9 correlation with NOTCH1 involved in Notch signaling in metastatic breast cancer. The Notch signaling pathway has been approved to be associated with the development and progression of many human cancers, including breast cancer, but the precise mechanism has remained unknown. To the best of our knowledge, this is the first study that introduces miR-9 and NOTCH1 correlation as an effective factor in breast cancer. We found that miR-9 expression was decreased in MDA-MB-231 breast cancer cells compared with MCF-10A normal breast cell line. However, NOTCH1 was upregulated in the metastatic breast cancer cells. Furthermore, luciferase assay revealed a significant inverse correlation between miR-9 and NOTCH1. Overexpression of Notch signaling via Notch1 intracellular domain in MDA-MB-231 cell line was suppressed by lentiviruses expressing miR-9. Taken together, the results obtained by MTT, flow cytometry, migration, and wound healing assays showed that it is possible to inhibit metastasis and induce pro-apoptotic state by induction of miR-9 expression in MDA-MB-231 cells but with no effect on cell proliferation. These results shows that miR-9, by direct targeting of NOTCH1, can reveal a suppressor-like activity in metastatic breast cancer cells.

  4. 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....

  5. 5-Azacytidine Induces Anoikis, Inhibits Mammosphere Formation and Reduces Metalloproteinase 9 Activity in MCF-7 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hsueh-Wei Chang

    2014-03-01

    Full Text Available Cancer stem cells are a subset of cancer cells that initiate the growth of tumors. Low levels of cancer stem cells also exist in established cancer cell lines, and can be enriched in serum-free tumorsphere cultures. Since cancer stem cells have been reported to be resilient to common chemotherapeutic drugs in comparison to regular cancer cells, screening for compounds selectively targeting cancer stem cells may provide an effective therapeutic strategy. We found that 5-azacytidine (5-AzaC selectively induced anoikis of MCF-7 in suspension cultures with an EC50 of 8.014 µM, and effectively inhibited tumorsphere formation, as well as the migration and matrix metalloproteinases-9 (MMP-9 activity of MCF-7 cells. Furthermore, 5-AzaC and radiation collaboratively inhibited MCF-7 tumorsphere formation at clinically relevant radiation doses. Investigating the underlying mechanism may provide insight into signaling pathways crucial for cancer stem cell survival and pave the way to novel potential therapeutic targets.

  6. Inhibition of ALDH1A1 activity decreases expression of drug transporters and reduces chemotherapy resistance in ovarian cancer cell lines.

    Science.gov (United States)

    Januchowski, Radosław; Wojtowicz, Karolina; Sterzyńska, Karolina; Sosińska, Patrycja; Andrzejewska, Małgorzata; Zawierucha, Piotr; Nowicki, Michał; Zabel, Maciej

    2016-09-01

    The high mortality of ovarian cancer patients results from the failure of treatment caused by the inherent or acquired chemotherapy drug resistance. It was reported that overexpression of aldehyde dehydrogenase A1 (ALDH1A1) in cancer cells can be responsible for the development of drug resistance. To add the high expression of the drug transporter proteins the ALDHA1 is considered as a molecular target in cancer therapy. Therefore, we analysed drug-resistant ovarian cancer cell lines according to ALDHA1 expression and the association with drug resistance. The expression of ALDH1A1, P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) was determined using a microarray and confirmed by Q-PCR, western blot and fluorescence analysis. ALDH1A1 activity was determined using an Aldefluor assay. The impact of all-trans retinoic acid (ATRA) and diethylaminobenzaldehyde (DEAB) on chemotherapy resistance was assessed by the MTT chemosensitivity assay. The most abundant expression of ALDH1A1 was noted in paclitaxel- and topotecan-resistant cell lines where two populations of ALDH-positive and ALDH-negative cells could be observed. Those cell lines also revealed the overexpression of P-gp and BCRP respectively, and were able to form spheres in non-adherent conditions. Pre-treatment with ATRA and DEAB reduced chemotherapy resistance in both cell lines. ATRA treatment led to downregulation of the ALDH1A1, P-gp and BCRP proteins. DEAB treatment led to downregulation of the P-gp protein and BCRP transcript and protein. Our results indicate that ALDH1A1-positive cancer cells can be responsible for drug resistance development in ovarian cancer. Developing more specific ALDH1A1 inhibitors can increase chemotherapy effectiveness in ovarian cancer.

  7. Nanostructured zirconia decorated reduced graphene oxide based efficient biosensing platform for non-invasive oral cancer detection.

    Science.gov (United States)

    Kumar, Suveen; Sharma, Jai Gopal; Maji, Sagar; Malhotra, Bansi Dhar

    2016-04-15

    We report results of the studies relating to fabrication of a non-invasive, label-free and an efficient biosensing platform for detection of the oral cancer biomarker (CYFRA-21-1). One step hydrothermal process was used for uniform decoration of nanostructured zirconia (average particle size 13 nm) on reduced graphene oxide (ZrO2-RGO) to avoid coagulation of the zirconia nanoparticles and to obtain enhanced electrochemical performance of ZrO2-RGO nanocomposite based biosensor. Further, ZrO2-RGO has been functionalized using 3-aminopropyl triethoxy saline (APTES) and electrophoretically deposited on the indium tin oxide coated glass substrate at a low DC potential.The APTES/ZrO2-RGO/ITO electrode exhibits improved heterogeneous electron transfer (more than two times) with respect to that of the APTES/ZrO2/ITO electrode indicating faster electron transfer kinetics. The -NH2 containing APTES/ZrO2-RGO/ITO platform is further biofunctionalized with anti-CYFRA-21-1. The structural and morphological investigations of the ZrO2-RGO based biosensing platform have been accomplished using X-ray diffraction (XRD), electrochemical, transmission electron microscopy (TEM), atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FT-IR) studies. This immunosensor exhibits a wider linear detection range (2-22 ng mL(-1)), excellent sensitivity (0.756 µA mL ng(-1)) and a remarkable lower detection limit of 0.122 ng mL(-1). The observed results have been validated via enzyme linked immunosorbent assay (ELISA).

  8. Nanostructured zirconia decorated reduced graphene oxide based efficient biosensing platform for non-invasive oral cancer detection.

    Science.gov (United States)

    Kumar, Suveen; Sharma, Jai Gopal; Maji, Sagar; Malhotra, Bansi Dhar

    2016-04-15

    We report results of the studies relating to fabrication of a non-invasive, label-free and an efficient biosensing platform for detection of the oral cancer biomarker (CYFRA-21-1). One step hydrothermal process was used for uniform decoration of nanostructured zirconia (average particle size 13 nm) on reduced graphene oxide (ZrO2-RGO) to avoid coagulation of the zirconia nanoparticles and to obtain enhanced electrochemical performance of ZrO2-RGO nanocomposite based biosensor. Further, ZrO2-RGO has been functionalized using 3-aminopropyl triethoxy saline (APTES) and electrophoretically deposited on the indium tin oxide coated glass substrate at a low DC potential.The APTES/ZrO2-RGO/ITO electrode exhibits improved heterogeneous electron transfer (more than two times) with respect to that of the APTES/ZrO2/ITO electrode indicating faster electron transfer kinetics. The -NH2 containing APTES/ZrO2-RGO/ITO platform is further biofunctionalized with anti-CYFRA-21-1. The structural and morphological investigations of the ZrO2-RGO based biosensing platform have been accomplished using X-ray diffraction (XRD), electrochemical, transmission electron microscopy (TEM), atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FT-IR) studies. This immunosensor exhibits a wider linear detection range (2-22 ng mL(-1)), excellent sensitivity (0.756 µA mL ng(-1)) and a remarkable lower detection limit of 0.122 ng mL(-1). The observed results have been validated via enzyme linked immunosorbent assay (ELISA). PMID:26657594

  9. 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. PMID:23718957

  10. 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

    OpenAIRE

    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...

  11. Inhibition of STAT3, FAK and Src mediated signaling reduces cancer stem cell load, tumorigenic potential and metastasis in breast cancer

    OpenAIRE

    Thakur, Ravi; Trivedi, Rachana; Rastogi, Namrata; Singh, Manisha; Mishra, Durga Prasad

    2015-01-01

    Cancer stem cells (CSCs) are responsible for aggressive tumor growth, metastasis and therapy resistance. In this study, we evaluated the effects of Shikonin (Shk) on breast cancer and found its anti-CSC potential. Shk treatment decreased the expression of various epithelial to mesenchymal transition (EMT) and CSC associated markers. Kinase profiling array and western blot analysis indicated that Shk inhibits STAT3, FAK and Src activation. Inhibition of these signaling proteins using standard ...

  12. Association of Vitamin E Intake with Reduced Risk of Kidney Cancer: A Meta-Analysis of Observational Studies

    OpenAIRE

    Shen, Chongxing; Huang, Ying; Yi, Shanhong; Fang, Zhenqiang; Li, Longkun

    2015-01-01

    Background Several observational studies suggested that vitamin E intake is related to the risk of kidney cancer; however, the results of published studies are inconsistent. Material/Methods A meta-analysis was performed to assess the relationship between vitamin E intake and the risk of kidney cancer by searching PubMed and Medline through August 2015. We computed pooled relative risks (RR) and 95%CI of kidney cancer for the highest versus lowest level of vitamin E intake. Results A total of...

  13. Global gene expression analysis reveals reduced abundance of putative microRNA targets in human prostate tumours

    Directory of Open Access Journals (Sweden)

    Xie Yi

    2009-02-01

    Full Text Available Abstract Background Recently, microRNAs (miRNAs have taken centre stage in the field of human molecular oncology. Several studies have shown that miRNA profiling analyses offer new possibilities in cancer classification, diagnosis and prognosis. However, the function of miRNAs that are dysregulated in tumours remains largely a mystery. Global analysis of miRNA-target gene expression has helped illuminate the role of miRNAs in developmental gene expression programs, but such an approach has not been reported in cancer transcriptomics. Results In this study, we globally analysed the expression patterns of miRNA target genes in prostate cancer by using several public microarray datasets. Intriguingly, we found that, in contrast to global mRNA transcript levels, putative miRNA targets showed a reduced abundance in prostate tumours relative to benign prostate tissue. Additionally, the down-regulation of these miRNA targets positively correlated with the number of types of miRNA target-sites in the 3' untranslated regions of these targets. Further investigation revealed that the globally low expression was mainly driven by the targets of 36 specific miRNAs that were reported to be up-regulated in prostate cancer by a miRNA expression profiling study. We also found that the transcript levels of miRNA targets were lower in androgen-independent prostate cancer than in androgen-dependent prostate cancer. Moreover, when the global analysis was extended to four other cancers, significant differences in transcript levels between miRNA targets and total mRNA backgrounds were found. Conclusion Global gene expression analysis, along with further investigation, suggests that miRNA targets have a significantly reduced transcript abundance in prostate cancer, when compared with the combined pool of all mRNAs. The abnormal expression pattern of miRNA targets in human cancer could be a common feature of the human cancer transcriptome. Our study may help to shed new

  14. Cancer

    Science.gov (United States)

    ... Blood tests (which look for chemicals such as tumor markers) Bone marrow biopsy (for lymphoma or leukemia) Chest ... the case with skin cancers , as well as cancers of the lung, breast, and colon. If the tumor has spread ...

  15. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  16. 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

    was obtained from high-quality national population-based registries. A literature review was conducted to define the fraction of these lesions attributable to HPV16/18, i.e., those that could be prevented by HPV vaccination. RESULTS: Among the four countries, the age-standardised IR/10⁵ of cervical, vaginal......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...

  17. Music in Reducing Anxiety and Pain in Adult Patients Undergoing Bone Marrow Biopsy for Hematologic Cancers or Other Diseases

    Science.gov (United States)

    2012-07-12

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Psychosocial Effects of Cancer and Its Treatment

  18. Conquer fear: protocol of a randomised controlled trial of a psychological intervention to reduce fear of cancer recurrence

    OpenAIRE

    Butow, Phyllis N.; Bell, Melanie L; Smith, Allan B; Fardell, Joanna E.; Thewes, Belinda; Turner, Jane; Gilchrist, Jemma; Beith, Jane; Girgis, Afaf; Sharpe, Louise; Shih, Sophy; Mihalopoulos, Cathrine

    2013-01-01

    Background Up to 70% of cancer survivors report clinically significant levels of fear of cancer recurrence (FCR). Despite the known negative impact of FCR on psychological wellbeing and quality of life, little research has investigated interventions for high FCR. Our team has developed and piloted a novel intervention (Conquer Fear) based on the Self-Regulatory Executive Function Model and Relational Frame Theory and is evaluating Conquer Fear in a randomised controlled trial (RCT). We aim to...

  19. Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

    Directory of Open Access Journals (Sweden)

    Euphemia Yee Leung

    2014-09-01

    Full Text Available The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, docetaxel and hydrogen peroxide. The mechanisms underlying these changes have not yet been characterized but may include a shift from glycolysis to mitochondrial respiration. If this phenotype is found in clinical hormone-resistant breast cancers, conventional cytotoxic therapy may be a preferred option for treatment.

  20. Transcriptome Profiling Reveals the Antitumor Mechanism of Polysaccharide from Marine Algae Gracilariopsis lemaneiformis

    Science.gov (United States)

    Li, Hua; Wu, Jun; Xu, Xiaoting; Sun, Xue; Zhao, Xiaodong; Xu, Nianjun

    2016-01-01

    Seaweed is one of the important biomass producers and possesses active metabolites with potential therapeutic effects against tumors. The red alga Gracilariopsis lemaneiformis (Gp. lemaneiformis) possesses antitumor activity, and the polysaccharide of Gp. lemaneiformis (PGL) has been demonstrated to be an ingredient with marked anticancer activity. However, the anticancer mechanism of PGL remains to be elucidated. In this study, we analyzed the inhibitory effect of PGL on the cell growth of 3 human cancer cell lines and found that PGL inhibited cell proliferation, reduced cell viability, and altered cell morphology in a time- and concentration-dependent manner. Our transcriptome analysis indicates that PGL can regulate the expression of 758 genes, which are involved in apoptosis, the cell cycle, nuclear division, and cell death. Furthermore, we demonstrated that PGL induced apoptosis and cell cycle arrest and modulated the expression of related genes in the A549 cell line. Our work provides a framework to understand the effects of PGL on cancer cells, and can serve as a resource for delineating the antitumor mechanisms of Gp. lemaneiformis. PMID:27355352

  1. HR-MAS MRS of the pancreas reveals reduced lipid and elevated lactate and taurine associated with early pancreatic cancer.

    Science.gov (United States)

    Wang, Alan S; Lodi, Alessia; Rivera, Lee B; Izquierdo-Garcia, Jose L; Firpo, Matthew A; Mulvihill, Sean J; Tempero, Margaret A; Bergers, Gabriele; Ronen, Sabrina M

    2014-11-01

    The prognosis for patients with pancreatic cancer is extremely poor, as evidenced by the disease's five-year survival rate of ~5%. New approaches are therefore urgently needed to improve detection, treatment, and monitoring of pancreatic cancer. MRS-detectable metabolic changes provide useful biomarkers for tumor detection and response-monitoring in other cancers. The goal of this study was to identify MRS-detectable biomarkers of pancreatic cancer that could enhance currently available imaging approaches. We used (1) H high-resolution magic angle spinning MRS to probe metabolite levels in pancreatic tissue samples from mouse models and patients. In mice, the levels of lipids dropped significantly in pancreata with lipopolysaccharide-induced inflammation, in pancreata with pre-cancerous metaplasia (4 week old p48-Cre;LSL-Kras(G12D) mice), and in pancreata with pancreatic intraepithelial neoplasia, which precedes invasive pancreatic cancer (8 week old p48-Cre LSL-Kras(G12D) mice), to 26 ± 19% (p = 0.03), 19 ± 16% (p = 0.04), and 26 ± 10% (p = 0.05) of controls, respectively. Lactate and taurine remained unchanged in inflammation and in pre-cancerous metaplasia but increased significantly in pancreatic intraepithelial neoplasia to 266 ± 61% (p = 0.0001) and 999 ± 174% (p pancreatitis and in invasive cancer biopsies to 29 ± 15% (p = 0.01) and 26 ± 38% (p = 0.02) of normal tissue. In addition, lactate and taurine levels remained unchanged in inflammation but rose in tumor samples to 244 ± 155% (p = 0.02) and 188 ± 67% (p = 0.02), respectively, compared with normal tissue. Based on these findings, we propose that a drop in lipid levels could serve to inform on pancreatitis and cancer-associated inflammation, whereas elevated lactate and taurine could serve to identify the presence of pancreatic intraepithelial neoplasia and invasive tumor. Our findings may help enhance current imaging methods to improve early pancreatic cancer detection and monitoring.

  2. Brefeldin A Reduces Anchorage-Independent Survival, Cancer Stem Cell Potential and Migration of MDA-MB-231 Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chao-Neng Tseng

    2014-10-01

    Full Text Available Cancer stem cells (CSCs are a subset of cancer cells in tumors or established cancer cell lines that can initiate and sustain the growth of tumors in vivo. Cancer stem cells can be enriched in serum-free, suspended cultures that allow the formation of tumorspheres over several days to weeks. Brefeldin A (BFA is a mycotoxin that induces endoplasmic reticulum (ER stress in eukaryotic cells. We found that BFA, at sub-microgram per milliliter concentrations, preferentially induced cell death in MDA-MB-231 suspension cultures (EC50: 0.016 µg/mL compared to adhesion cultures. BFA also effectively inhibited clonogenic activity and the migration and matrix metalloproteinases-9 (MMP-9 activity of MDA-MB-231 cells. Western blotting analysis indicated that the effects of BFA may be mediated by the down-regulation of breast CSC marker CD44 and anti-apoptotic proteins Bcl-2 and Mcl-1, as well as the reversal of epithelial-mesenchymal transition. Furthermore, BFA also displayed selective cytotoxicity toward suspended MDA-MB-468 cells, and suppressed tumorsphere formation in T47D and MDA-MB-453 cells, suggesting that BFA may be effective against breast cancer cells of various phenotypes.

  3. Integration of transcriptomics and metabonomics

    DEFF Research Database (Denmark)

    Bjerrum, Jacob Tveiten; Rantalainen, Mattias; Wang, Yulan;

    2014-01-01

    A systems biology approach to multi-faceted diseases has provided an opportunity to establish a holistic understanding of the processes at play. Thus, the current study merges transcriptomics and metabonomics data in order to improve diagnostics, biomarker identification and to explore the possib......A systems biology approach to multi-faceted diseases has provided an opportunity to establish a holistic understanding of the processes at play. Thus, the current study merges transcriptomics and metabonomics data in order to improve diagnostics, biomarker identification and to explore...... profiles were generated using (1)H Nuclear magnetic resonance spectroscopy (Bruker 600 MHz, Bruker BioSpin, Rheinstetten, Germany). Data were analyzed with the use of orthogonal-projection to latent structure-discriminant analysis and a multivariate logistic regression model fitted by lasso. Prediction....... These combined panels improve diagnostics and more importantly also the molecular phenotyping in UC and provide insight into the pathophysiological processes at play, making optimized and personalized medication a possibility....

  4. Tricks to translating TB transcriptomics.

    Science.gov (United States)

    Deffur, Armin; Wilkinson, Robert J; Coussens, Anna K

    2015-05-01

    Transcriptomics and other high-throughput methods are increasingly applied to questions relating to tuberculosis (TB) pathogenesis. Whole blood transcriptomics has repeatedly been applied to define correlates of TB risk and has produced new insight into the late stage of disease pathogenesis. In a novel approach, authors of a recently published study in Science Translational Medicine applied complex data analysis of existing TB transcriptomic datasets, and in vitro models, in an attempt to identify correlates of protection in TB, which are crucially required for the development of novel TB diagnostics and therapeutics to halt this global epidemic. Utilizing latent TB infection (LTBI) as a surrogate of protection, they identified IL-32 as a mediator of interferon gamma (IFNγ)-vitamin D dependent antimicrobial immunity and a marker of LTBI. Here, we provide a review of all TB whole-blood transcriptomic studies to date in the context of identifying correlates of protection, discuss potential pitfalls of combining complex analyses originating from such studies, the importance of detailed metadata to interpret differential patient classification algorithms, the effect of differing circulating cell populations between patient groups on the interpretation of resulting biomarkers and we decipher weighted gene co-expression network analysis (WGCNA), a recently developed systems biology tool which holds promise of identifying novel pathway interactions in disease pathogenesis. In conclusion, we propose the development of an integrated OMICS platform and open access to detailed metadata, in order for the TB research community to leverage the vast array of OMICS data being generated with the aim of unraveling the holy grail of TB research: correlates of protection. PMID:26046091

  5. Hormone Resistance in Two MCF-7 Breast Cancer Cell Lines is Associated with Reduced mTOR Signaling, Decreased Glycolysis, and Increased Sensitivity to Cytotoxic Drugs

    OpenAIRE

    Leung, Euphemia Yee; Kim, Ji Eun; Askarian-Amiri, Marjan; Joseph, Wayne R.; McKeage, Mark J; Baguley, Bruce C.

    2014-01-01

    The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume, and resistance to mTOR inhibition. Here, we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, d...

  6. Hormone resistance in two MCF-7 breast cancer cell lines is associated with reduced mTOR signaling, decreased glycolysis and increased sensitivity to cytotoxic drugs

    OpenAIRE

    Euphemia Yee Leung; Ji Eun eKim; Marjan eAskarian-Amiri; Joseph, Wayne R.; McKeage, Mark J; Bruce Charles Baguley

    2014-01-01

    The mTOR pathway is a key regulator of multiple cellular signaling pathways and is a potential target for therapy. We have previously developed two hormone-resistant sub-lines of the MCF-7 human breast cancer line, designated TamC3 and TamR3, which were characterized by reduced mTOR signaling, reduced cell volume and resistance to mTOR inhibition. Here we show that these lines exhibit increased sensitivity to carboplatin, oxaliplatin, 5-fluorouracil, camptothecin, doxorubicin, paclitaxel, doc...

  7. Co-existence of Echinococcus granulosus infection and cancer metastasis in the liver correlates with reduced Th1 immune responses.

    Science.gov (United States)

    Turhan, N; Esendagli, G; Ozkayar, O; Tunali, G; Sokmensuer, C; Abbasoglu, O

    2015-01-01

    A possible relationship between cancer and Echinococcus granulosus infection has been postulated. As T cells are critical players in immune responses against both infections and malignancies, in an experimental model of secondary echinococcosis and breast cancer, this study aims to observe the progression of cancer and to determine the characters of T-cell responses. 4T1 breast tumour cells were subcutaneously injected into mammary region, whereas protoscoleces were intraperitoneally inoculated into the mice. Hydatid cysts, tumours and metastases were determined with macroscopic and histopathological evaluation. T cells found in spleen, liver and tumour were characterised by flow cytometric analysis of CD3, CD4, CD8, CD25, CCR5, CCR3, IL-4 and IFN-γ. In the mice inoculated both with protoscoleces and with breast tumour cells, increased frequency of cancer metastasis was observed in the liver. The amount of CD4(+) T cells was increased in the liver and in the spleen of mice infected with E. granulosus. However, co-existence of echinococcosis and metastatic lesions in the liver was associated with significant reduction in the IFN-γ(+) and CCR5(+) Th1 cells and increase in the CD25(+) T cells. Our results may indicate an immunological link between cystic echinococcosis and cancer that allows tumour metastasis to flourish in the liver.

  8. Reduced radiation dose for elective nodal irradiation in node-negative anal cancer: back to the roots

    Energy Technology Data Exchange (ETDEWEB)

    Henkenberens, Christoph; Meinecke, Daniela; Bremer, Michael; Christiansen, Hans [Medizinische Hochschule Hannover, Hannover Medical School, Department of Radiation Oncology, Klinik fuer Strahlentherapie und Spezielle Onkologie, Hannover (Germany); Michael, Stoll [End- und Dickdarmzentrum Hannover, Hannover (Germany)

    2015-11-15

    Chemoradiation (CRT) is the standard of care in patients with node-positive (cN+) and node-negative (cN0) anal cancer. Depending on the tumor size (T-stage), total doses of 50-60 Gray (Gy) in daily fractions of 1.8-2.0 Gy are usually applied to the tumor site. Inguinal and iliac lymph nodes usually receive a dose of ≥ 45 Gy. Since 2010, our policy has been to apply a reduced total dose of 39.6 Gy to uninvolved nodal regions. This paper provides preliminary results of the efficacy and safety of this protocol. Overall, 30 patients with histologically confirmed and node-negative anal cancer were treated in our department from 2009-2014 with definitive CRT. Histology all cases showed squamous cell carcinoma. A total dose of 39.6 Gy [single dose (SD) 1.8 Gy] was delivered to the iliac/inguinal lymph nodes. The area of the primary tumor received 50-59.4 Gy, depending on the T-stage. In parallel with the irradiation, 5-fluorouracil (5-FU) at a dose of 1000 mg/m{sup 2} was administered by continuous intravenous infusion over 24 h on days 1-4 and 29-32, and mitomycin C (MMC) at a dose of 10 mg/m{sup 2} (maximum absolute dose 14 mg) was administered on days 1 and 29. The distribution of the tumor stages was as follows: T1, n = 8; T2, n = 17; T3 n = 3. Overall survival (OS), local control (LC) of the lymph nodes, colostomy-free survival (CFS), and acute and chronic toxicities were assessed. The median follow-up was 27.3 months (range 2.7-57.4 months). Three patients (10.0 %) died, 2 of cardiopulmonary diseases and one of liver failure, yielding a 3-year OS of 90.0 %. Two patients (6.7 %) relapsed early and received salvage colostomies, yielding a 3-year CFS of 93.3 %. No lymph node relapses were observed, giving a lymph node LC of 100 %. According to the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE V. 4.0), there were no grade IV gastrointestinal or genitourinary acute toxicities. Seven patients showed acute grade III perineal skin toxicity. Acute grade

  9. A special device (double-hole belly board) and optimal radiation technique to reduce testicular radiation exposure in radiotherapy of rectal cancer

    International Nuclear Information System (INIS)

    Purpose: Patients with rectal cancer are treated in prone position on a belly board to reduce the volume of irradiated small bowel. With this technique the testes obtain radiation doses, which often result in partial or complete impairment of the spermatogenesis and a dose-dependent decrease of testosterone levels. We developed a double-hole belly board (DHBB) and evaluated its potential to reduce testicular dose. Methods and materials: In nine consecutive male patients (3 very low tumor localisations [inguinal RT], 3 low [RT perineum], 3 high [lower border ischial tuberosities]) CT scans were performed on a conventional single-hole belly board (SHBB) and on a DHBB. Dose-volume histograms of the testes were analysed for both belly boards and for different treatment techniques (3-field and 4-field). Results: To reduce testicular dose in high tumors, positioning on DHBB was most effective (V1.5Gy 20-30% vs. 60% for SHBB, V4Gy 7% vs. 35%). In low tumors, a 3-field technique reduced high testicular doses (V14Gy 0-6% vs. 28-34% for 4-fields). In very low tumors a combination of DHBB and 3-fields led to a decrease of high dose exposure (V33Gy 0% vs. 24-78%). Conclusion: In male patients with rectal cancer the use of a DHBB and a 3-field technique is recommended to reduce testicular radiation exposure

  10. Reduced expression of Toll-like receptor 4 inhibits human breast cancer cells proliferation and inflammatory cytokines secretion

    Directory of Open Access Journals (Sweden)

    Xie Xiaofang

    2010-07-01

    Full Text Available Abstract Background Tumor cell expression of Toll-like receptors (TLRs can promote inflammation and cell survival in the tumor microenvironment. Toll-like receptor 4 (TLR4 signaling in tumor cells can mediate tumor cell immune escape and tumor progression, and it is regarded as one of the mechanisms for chronic inflammation in tumorigenesis and progression. The expression of TLR4 in human breast cancer cell line MDA-MB-231 and its biological function in the development and progression of breast cancer have not been investigated. We sought to characterize the expression of TLR1-TLR10 in the established human breast cancer cell line MDA-MB-231, and to investigate the biological roles of TLR4 in breast cancer cells growth, survival, and its potential as a target for breast cancer therapy. Methods TLRs mRNA and protein expressions were detected in human breast cancer cell line MDA-MB-231 by RT-PCR, real-time PCR and flow cytometry (FCM. RNA interference was used to knockdown the expression of TLR4 in MDA-MB-231. MDA-MB-231 transfected with the vector pGenesil-1 and the vector containing a scrambled siRNA were as controls. Recombinant plasmids named TLR4AsiRNA, TLR4BsiRNA and TLR4CsiRNA specific to TLR4 were transfected into human breast cancer cell line MDA-MB-231 with Lipfectamine™2000 reagent. TLR4 mRNA and protein expressions were investigated by RT-PCR, real-time PCR, FCM and immunofluorescence after silence. MTT analysis was performed to detect cell proliferation and FCM was used to detect the secretion of inflammatory cytokines in supernatant of transfected cells. Results The human breast cancer cell line MDA-MB-231 was found to express TLR1-TLR10 at both the mRNA and protein levels. TLR4 was found to be the highest expressed TLR in MDA-MB-231. TLR4AsiRNA, TLR4BsiRNA and TLR4CsiRNA were found to significantly inhibit TLR4 expression in MDA-MB-231 at both mRNA and protein levels as compared to vector control(vector transfected cells. TLR4Asi

  11. Exercise may reduce depression but not anxiety in self-referred cancer patients undergoing chemotherapy. Post-hoc analysis of data from the 'Body & Cancer' trial

    DEFF Research Database (Denmark)

    Midtgaard, Julie; Stage, Maria; Møller, Tom;

    2011-01-01

    chemotherapy (The 'Body & Cancer' trial). Methods. Two hundred and nine self-referred patients (52 males, 157 females, mean age 47 years) were randomised into an intervention group and a waiting-list control group. Anxiety and depression was measured by the Hospital Anxiety and Depression Scale. Results...

  12. GPER mediated estradiol reduces miR-148a to promote HLA-G expression in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Sifeng, E-mail: taosifeng@aliyun.com; He, Haifei; Chen, Qiang; Yue, Wenjie

    2014-08-15

    Highlights: • E2 induces the level of miR-148a in MCF-7 and MDA-MB-231 cells. • GPER mediates the E2-induced increase of miR-148a in MCF-7 and MDA-MB-231 cells. • E2-GPER regulates the expression of HLA-G by miR-148a. - Abstract: Breast cancer is the most common malignant diseases in women. miR-148a plays an important role in regulation of cancer cell proliferation and cancer invasion and down-regulation of miR-148a has been reported in both estrogen receptor (ER) positive and triple-negative (TN) breast cancer. However, the regulation mechanism of miR-148a is unclear. The role of estrogen signaling, a signaling pathway is important in development and progression of breast cancer. Therefore, we speculated that E2 may regulate miR-148a through G-protein-coupled estrogen receptor-1 (GPER). To test our hypothesis, we checked the effects of E2 on miR-148a expression in ER positive breast cancer cell MCF-7 and TN cancer cell MDA-MB-231. Then we used GPER inhibitor G15 to investigate whether GPER is involved in regulation of E2 on miR-148a. Furthermore, we analyzed whether E2 affects the expression of HLA-G, which is a miR-148a target gene through GPER. The results showed that E2 induces the level of miR-148a in MCF-7 and MDA-MB-231 cells, GPER mediates the E2-induced increase in miR-148a expression in MCF-7 and MDA-MB-231 cells and E2-GPER regulates the expression of HLA-G by miR-148a. In conclusion, our findings offer important new insights into the ability of estrogenic GPER signaling to trigger HLA-G expression through inhibiting miR-148a that supports immune evasion in breast cancer.

  13. Improved xenobiotic metabolism and reduced susceptibility to cancer in gluten-sensitive macaques upon introduction of a gluten-free diet.

    Directory of Open Access Journals (Sweden)

    Karol Sestak

    Full Text Available BACKGROUND: A non-human primate (NHP model of gluten sensitivity was employed to study the gene perturbations associated with dietary gluten changes in small intestinal tissues from gluten-sensitive rhesus macaques (Macaca mulatta. METHODOLOGY: Stages of remission and relapse were accomplished in gluten-sensitive animals by administration of gluten-free (GFD and gluten-containing (GD diets, as described previously. Pin-head-sized biopsies, obtained non-invasively by pediatric endoscope from duodenum while on GFD or GD, were used for preparation of total RNA and gene profiling, using the commercial Rhesus Macaque Microarray (Agilent Technologies,targeting expression of over 20,000 genes. PRINCIPAL FINDINGS: When compared with normal healthy control, gluten-sensitive macaques showed differential gene expressions induced by GD. While observed gene perturbations were classified into one of 12 overlapping categories--cancer, metabolism, digestive tract function, immune response, cell growth, signal transduction, autoimmunity, detoxification of xenobiotics, apoptosis, actin-collagen deposition, neuronal and unknown function--this study focused on cancer-related gene networks such as cytochrome P450 family (detoxification function and actin-collagen-matrix metalloproteinases (MMP genes. CONCLUSIONS/SIGNIFICANCE: A loss of detoxification function paralleled with necessity to metabolize carcinogens was revealed in gluten-sensitive animals while on GD. An increase in cancer-promoting factors and a simultaneous decrease in cancer-preventing factors associated with altered expression of actin-collagen-MMP gene network were noted. In addition, gluten-sensitive macaques showed reduced number of differentially expressed genes including the cancer-associated ones upon withdrawal of dietary gluten. Taken together, these findings indicate potentially expanded utility of gluten-sensitive rhesus macaques in cancer research.

  14. [Cancer].

    Science.gov (United States)

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer. PMID:27603890

  15. Inhibition of formyl peptide receptor 1 reduces the efficacy of anticancer chemotherapy against carcinogen-induced breast cancer.

    Science.gov (United States)

    Baracco, Elisa E; Pietrocola, Federico; Buqué, Aitziber; Bloy, Norma; Senovilla, Laura; Zitvogel, Laurence; Vacchelli, Erika; Kroemer, Guido

    2016-06-01

    The loss-of-function mutation of formyl peptide receptor 1 (FPR1) has a negative impact on the progression-free and overall survival of breast cancer patients treated with anthracycline-based adjuvant chemotherapy. This effect may be attributed to the fact that chemotherapy-induced antitumor immunity requires FPR1 and that such anticancer immune responses are responsible for the long-term effects of chemotherapy. Here, we investigated the possible contribution of FPR1 to the efficacy of a combination of mitoxantrone (MTX) and cyclophosphamide (CTX) for the treatment of hormone-induced breast cancer. Breast cancer induced by a combination of medroxyprogesterone acetate (MPA) and 7,12-Dimethylbenz[a]anthracene (DMBA) could be successfully treated with MTX plus CTX in thus far that tumor growth was retarded and overall survival was extended (as compared to vehicle-only treated controls). However, the therapeutic efficacy of the combination therapy was completely abolished when FPR1 receptors were blocked by means of cyclosporin H (CsH). Future genetic studies on neoadjuvant chemotherapy-treated breast cancers are warranted to validate these findings at the clinical level. PMID:27471610

  16. Restoring KLF5 in esophageal squamous cell cancer cells activates the JNK pathway leading to apoptosis and reduced cell survival.

    Science.gov (United States)

    Tarapore, Rohinton S; Yang, Yizeng; Katz, Jonathan P

    2013-05-01

    Esophageal cancer is the eighth most common cancer in the world and has an extremely dismal prognosis, with a 5-year survival of less than 20%. Current treatment options are limited, and thus identifying new molecular targets and pathways is critical to derive novel therapies. Worldwide, more than 90% of esophageal cancers are esophageal squamous cell cancer (ESCC). Previously, we identified that Krüppel-like factor 5 (KLF5), a key transcriptional regulator normally expressed in esophageal squamous epithelial cells, is lost in human ESCC. To examine the effects of restoring KLF5 in ESCC, we transduced the human ESCC cell lines TE7 and TE15, both of which lack KLF5 expression, with retrovirus to express KLF5 upon doxycycline induction. When KLF5 was induced, ESCC cells demonstrated increased apoptosis and decreased viability, with up-regulation of the proapoptotic factor BAX. Interestingly, c-Jun N-terminal kinase (JNK) signaling, an important upstream mediator of proapoptotic pathways including BAX, was also activated following KLF5 induction. KLF5 activation of JNK signaling was mediated by KLF5 transactivation of two key upstream regulators of the JNK pathway, ASK1 and MKK4, and inhibition of JNK blocked apoptosis and normalized cell survival following KLF5 induction. Thus, restoring KLF5 in ESCC cells promotes apoptosis and decreases cell survival in a JNK-dependent manner, providing a potential therapeutic target for human ESCC.

  17. MicroRNA-10a is reduced in breast cancer and regulated in part through retinoic acid

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are short non-coding RNA molecules that play a critical role in mRNA cleavage and translational repression, and are known to be altered in many diseases including breast cancer. MicroRNA-10a (miR-10a) has been shown to be deregulated in various cancer types. The aim of this study was to investigate miR-10a expression in breast cancer and to further delineate the role of retinoids and thyroxine in regulation of miR-10a. Following informed patient consent and ethical approval, tissue samples were obtained during surgery. miR-10a was quantified in malignant (n = 103), normal (n = 30) and fibroadenoma (n = 35) tissues by RQ-PCR. Gene expression of Retinoic Acid Receptor beta (RARβ) and Thyroid Hormone receptor alpha (THRα) was also quantified in the same patient samples (n = 168). The in vitro effects of all-trans Retinoic acid (ATRA) and L-Thyroxine (T4) both individually and in combination, on miR-10a expression was investigated in breast cancer cell lines, T47D and SK-BR-3. The level of miR-10a expression was significantly decreased in tissues harvested from breast cancer patients (Mean (SEM) 2.1(0.07)) Log10 Relative Quantity (RQ)) compared to both normal (3.0(0.16) Log10 RQ, p < 0.001) and benign tissues (2.6(0.17) Log10 RQ, p < 0.05). The levels of both RARβ and THRα gene expression were also found to be decreased in breast cancer patients compared to controls (p < 0.001). A significant positive correlation was determined between miR-10a and RARβ (r = 0.31, p < 0.001) and also with THRα (r = 0.32, p < 0.001). In vitro stimulation assays revealed miR-10a expression was increased in both T47D and SK-BR-3 cells following addition of ATRA (2 fold (0.7)). While T4 alone did not stimulate miR-10a expression, the combination of T4 and ATRA was found to have a positive synergistic effect. The data presented supports a potential tumour suppressor role for miR-10a in breast cancer, and highlights retinoic acid as a positive regulator of the micro

  18. CanPrevent: a telephone-delivered intervention to reduce multiple behavioural risk factors for colorectal cancer

    Directory of Open Access Journals (Sweden)

    Hawkes Anna L

    2012-11-01

    Full Text Available Abstract Background This pilot study aimed to test the acceptability and short-term effectiveness of a telephone-delivered multiple health behaviour change intervention for relatives of colorectal cancer survivors. Methods A community-based sample of 22 first-degree relatives of colorectal cancer survivors were recruited via a media release. Data were collected at baseline and at six weeks (post-intervention. Outcome measures included health behaviours (physical activity, television viewing, diet, alcohol, body mass index, waist circumference and smoking, health-related quality of life (Short Form-36 and perceived colorectal cancer risk. Intervention satisfaction levels were also measured. The intervention included six telephone health coaching sessions, a participant handbook and a pedometer. It focused on behavioural risk factors for colorectal cancer [physical activity, diet (red and processed meat consumption, fruit and vegetable intake, alcohol, weight management and smoking], and colorectal cancer risk. Results From baseline to six weeks, improvements were observed for minutes moderate-vigorous physical activity (150.7 minutes, processed meat intake (−1.2 serves/week, vegetable intake (1 serve/day, alcohol intake (−0.4 standard drinks/day, body mass index (−1.4 kg/m2, and waist circumference (−5.1 cm. Improvements were also observed for physical (3.3 and mental (4.4 health-related quality of life. Further, compared with baseline, participants were more likely to meet Australian recommendations post-intervention for: moderate-vigorous physical activity (27.3 vs 59.1%; fruit intake (68.2 vs 81.8%; vegetable intake (4.6 vs 18.2%; alcohol consumption (59.1 vs 72.7%; body mass index (31.8 vs 45.5% and waist circumference (18.2 vs 27.3%. At six weeks participants were more likely to believe a diagnosis of CRC was related to family history, and there was a decrease in their perceived risk of developing CRC in their lifetime following

  19. Effectiveness of Mindfulness-based Therapy for Reducing Anxiety and Depression in Patients With Cancer: A Meta-analysis.

    Science.gov (United States)

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

    2015-11-01

    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 studies and did not

  20. The Role of Religious Psychotherapy with Independent Ruqyah in Reducing Depression and Improved Spiritual Quality of Life of Cancer Patients at Hospital of Hasanuddin University Makassar 2016

    Directory of Open Access Journals (Sweden)

    M. Fais Satrianegara

    2016-05-01

    Full Text Available This study aims to reveal the spiritual quality of life in cancer patients who receive spiritual support to the intervention of religious psychotherapy approaches as well as the efforts made to achieve a better life quality. The research method using pre-experimental one group pre and post test design with 10 respondent who were taken by purposive sampling technique. This study measured which measure depression score by using the instrument of BDI (Beck Depression Inventory and FACIT Sp.12 (The Functional Assessment of Chronic Illness Therapy Spiritual before and after the independent ruqyah and implement devotions sunnah in cancer patient who undergoing radiotherapy treatment in Hospital of Hasanuddin University, Makassar. Analysis of the data was analyzed using t-test. The results showed that there is a significant difference between levels of depression before and after the intervention (P <0.005. Cancer patients undergoing radiotherapy treatment and apply a independently ruqyah therapy consistently for 30 days can reduce levels of depression and improve the spiritual quality of life is better than before. The use of independent ruqyah can be considered as a palliative nursing interventions in the hospital for depression and in the framework of efforts in achieving the life quality of cancer patients.

  1. Overexpression of myeloid zinc finger 1 suppresses matrix metalloproteinase-2 expression and reduces invasiveness of SiHa human cervical cancer cells.

    Science.gov (United States)

    Tsai, Su-Ju; Hwang, Jin-Ming; Hsieh, Shu-Ching; Ying, Tsung-Ho; Hsieh, Yi-Hsien

    2012-08-24

    Myeloid zinc finger 1 (MZF1) gene belongs to the Kruppel family of zinc finger transcription factors. MZF1 has been suggested to play an important role in the tumorigenesis, invasion, and apoptosis of various tumor cells. However, the role of MZF1 in human cervical cancer remains unclear. To investigate the molecular mechanisms of MZF1 and its functional role in human cervical cancer cell migration and invasion, we experimented on stable SiHa cells overexpressing MZF1. We found that MZF1 overexpression inhibits the migratory and invasive abilities of SiHa cervical cancer cells. In addition, the overexpression of MZF1 significantly reduces MMP-2 protein and mRNA levels. Luciferase and ChIP assays suggested that MZF1 directly binds to MMP-2 gene regulatory sequences in vivo and suppresses MMP-2 promoter activity in vitro. This study shows that MZF-1 represses MMP-2 transcription and suggests that this repression may be linked to inhibition of human cervical cancer cell migration and metastasis.

  2. A High-Fat Diet Containing Lard Accelerates Prostate Cancer Progression and Reduces Survival Rate in Mice: Possible Contribution of Adipose Tissue-Derived Cytokines

    Directory of Open Access Journals (Sweden)

    Han Jin Cho

    2015-04-01

    Full Text Available To examine the effects of high-fat diet (HFD containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.

  3. Functional characterization of a promoter polymorphism in APE1/Ref-1 that contributes to reduced lung cancer susceptibility.

    Science.gov (United States)

    Lu, Juan; Zhang, Shuyu; Chen, Dan; Wang, Huibo; Wu, Wenting; Wang, Xiaotian; Lei, Yunping; Wang, Jiucun; Qian, Ji; Fan, Weiwei; Hu, Zhibin; Jin, Li; Shen, Hongbing; Huang, Wei; Wei, Qingyi; Lu, Daru

    2009-10-01

    Apurinic/apyrimidinic endonuclease 1/redox effector factor-1 (APE1/Ref-1) is a ubiquitous multifunctional protein that possesses both DNA-repair and redox regulatory activities. Although it was originally identified as a DNA-repair enzyme, accumulating evidence supports a role of APE1/Ref-1 in tumor development. To investigate association between APE1/Ref-1 polymorphisms and lung cancer risk in Chinese populations, we first genotyped three variants of APE1/Ref-1 and found a -141 T-to-G variant (rs1760944) in the promoter associated with decreased risk of lung cancer [odds ratio (OR) = 0.62 for GG; P=0.043]. Similar results were obtained in a follow-up replication study. Combined data from the two studies comprising a total of 1072 lung cancer patients and 1064 cancer-free control participants generated a more significant association (P=0.002). We observed lower APE1/Ref-1 mRNA levels in the presence of the protective G allele in human peripheral blood mononuclear cells and normal lung tissues. The -141G-allele-promoter construct exhibited decreased luciferase reporter gene expression. Electrophoretic mobility shift assays and surface plasmon resonance analysis showed that the -141G allele impaired the binding affinity of some transcription factor, accounting for lower APE1/Ref-1-promoter activity. Supershift assays further revealed that the protein of interest was octamer-binding transcription factor-1 (Oct-1). Chromatin immunoprecipitation reconfirmed binding of Oct-1 to the APE1/Ref-1 -141-promoter region. We also found that Oct-1 conferred attenuated transactivation capacity toward the -141G variant by exogenously introducing Oct-1. These data indicate that genetic variations in APE1/Ref-1 may modify susceptibility to lung cancer and provide new insights into an unexpected effect of APE1/Ref-1 on lung carcinogenesis.

  4. Obesity-mediated regulation of HGF/c-Met is associated with reduced basal-like breast cancer latency in parous mice.

    Directory of Open Access Journals (Sweden)

    Sneha Sundaram

    Full Text Available It is widely thought that pregnancy reduces breast cancer risk, but this lacks consideration of breast cancer subtypes. While a full term pregnancy reduces risk for estrogen receptor positive (ER+ and luminal breast cancers, parity is associated with increased risk of basal-like breast cancer (BBC subtype. Basal-like subtypes represent less than 10% of breast cancers and are highly aggressive, affecting primarily young, African American women. Our previous work demonstrated that high fat diet-induced obesity in nulliparous mice significantly blunted latency in C3(1-TAg mice, a model of BBC, potentially through the hepatocyte growth factor (HGF/c-Met oncogenic pathway. Experimental studies have examined parity and obesity individually, but to date, the joint effects of parity and obesity have not been studied. We investigated the role of obesity in parous mice on BBC. Parity alone dramatically blunted tumor latency compared to nulliparous controls with no effects on tumor number or growth, while obesity had only a minor role in further reducing latency. Obesity-associated metabolic mediators and hormones such as insulin, estrogen, and progesterone were not significantly regulated by obesity. Plasma IL-6 was also significantly elevated by obesity in parous mice. We have previously reported a potential role for stromal-derived hepatocyte growth factor (HGF via its cognate receptor c-Met in the etiology of obesity-induced BBC tumor onset and in both human and murine primary coculture models of BBC-aggressiveness. Obesity-associated c-Met concentrations were 2.5-fold greater in normal mammary glands of parous mice. Taken together, our studies demonstrate that, parity in C3(1-TAg mice dramatically reduced BBC latency compared to nulliparous mice. In parous mice, c-Met is regulated by obesity in unaffected mammary gland and is associated with tumor onset. C3(1-TAg mice recapitulate epidemiologic findings such that parity drives increased BBC risk and

  5. Evaluation of the Families SHARE workbook: an educational tool outlining disease risk and healthy guidelines to reduce risk of heart disease, diabetes, breast cancer and colorectal cancer

    OpenAIRE

    Koehly, Laura M.; Morris, Bronwyn A.; Skapinsky, Kaley; Goergen, Andrea; Ludden, Amanda

    2015-01-01

    Background Common diseases such as heart disease, diabetes, and cancer are etiologically complex with multiple risk factors (e.g., environment, genetic, lifestyle). These risk factors tend to cluster in families, making families an important social context for intervention and lifestyle-focused disease prevention. The Families Sharing Health Assessment and Risk Evaluation (SHARE) workbook was designed as an educational tool outlining family health history based risk of heart disease, type 2 d...

  6. Using Transcriptomics to Understand the Wheat Genome

    Science.gov (United States)

    Wheat (Triticum aestivum L.) is one of the most important food crops in the world, and transcriptomics studies of this crop promise to reveal the expression dynamics of genes that control many agriculturally important traits. In this review of wheat transcriptomics research, the current status of tr...

  7. Transfer of p14ARF gene in drug-resistant human breast cancer MCF-7/Adr cells inhibits proliferation and reduces doxorubicin resistance

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To elucidate the effect of p14ARF gene on multidrug-resistant tumor cells. Methods: We transferred a p14ARF cDNA into p53-mutated MCF-7/Adr human breast cancer cells. Results: In this report we demonstrated for the first time that p14ARF expression was able to greatly inhibit the MCF-7/Adr cell proliferation. Furthermore, p14ARF expression resulted in decreases in MDR1 mRNA and P-glycoprotein production, which linked with the reducing resistance of MCF-7/Adr cells to doxorubicin. Conclusion: These results imply that drug resistance might be effectively reversed with the wild-type p14ARF expression in human breast cancer cells.

  8. Transcriptome sequencing goals, assembly, and assessment.

    Science.gov (United States)

    Wheat, Christopher W; Vogel, Heiko

    2011-01-01

    Transcriptome sequencing provides quick, direct access to the mRNA. With this information, one can design primers for PCR of thousands of different genes, SNP markers, probes for microarrays and qPCR, or just use the sequence data itself in comparative studies. Transcriptome sequencing, while getting cheaper, is still an expensive endeavor, with an examination of data quality and its assembly infrequently performed in depth. Here, we outline many of the important issues we think need consideration when starting a transcriptome sequencing project. We also walk the reader through a detailed analysis of an example transcriptome dataset, highlighting the importance of both within-dataset analysis and comparative inferences. Our hope is that with greater attention focused upon assessing assembly performance, advances in transcriptome assembly will increase as prices continue to drop and new technologies, such as Illumina sequencing, start to be used. PMID:22065435

  9. SRC drives growth of antiestrogen resistant breast cancer cell lines and is a marker for reduced benefit of tamoxifen treatment

    DEFF Research Database (Denmark)

    Larsen, Sarah L; Laenkholm, Anne-Vibeke; Duun-Henriksen, Anne Katrine;

    2015-01-01

    screen on antiestrogen responsive T47D breast cancer cells and T47D-derived tamoxifen and fulvestrant resistant cell lines. We found that dasatinib, a broad-spectrum kinase inhibitor, inhibited growth of the antiestrogen resistant cells compared to parental T47D cells. Furthermore western blot analysis...... formed complexes with the Human Epidermal growth factor Receptor (HER)1 and HER2. Neither HER receptors nor ER were co-precipitated with Src in the tamoxifen resistant cell lines. Compared to treatment with dasatinib alone, combined treatment with dasatinib and fulvestrant had a stronger inhibitory...... effect on tamoxifen resistant cell growth, whereas dasatinib in combination with tamoxifen had no additive inhibitory effect on fulvestrant resistant growth. When performing immunohistochemical staining on 268 primary tumors from breast cancer patients who had received tamoxifen as first line endocrine...

  10. Acetylcysteine Rinse in Reducing Saliva Thickness and Mucositis in Patients With Head and Neck Cancer Undergoing Radiation Therapy

    Science.gov (United States)

    2016-02-04

    Mucositis; Oral Complications; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Adenoid Cystic Carcinoma of the Oral Cavity; Stage I Basal Cell Carcinoma of the Lip; Stage I Lymphoepithelioma of the Nasopharynx; Stage I Lymphoepithelioma of the Oropharynx; Stage I Mucoepidermoid Carcinoma of the Oral Cavity; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Adenoid Cystic Carcinoma of the Oral Cavity; Stage II Basal Cell Carcinoma of the Lip; Stage II Lymphoepithelioma of the Nasopharynx; Stage II Lymphoepithelioma of the Oropharynx; Stage II Mucoepidermoid Carcinoma of the Oral Cavity; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Adenoid Cystic Carcinoma of the Oral Cavity; Stage III Basal Cell Carcinoma of the Lip; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Lymphoepithelioma of the Oropharynx; Stage III Mucoepidermoid

  11. Kinesiology Taping reduces lymphedema of the upper extremity in women after breast cancer treatment: a pilot study

    OpenAIRE

    Iwona Malicka; Agnieszka Rosseger; Justyna Hanuszkiewicz; Marek Woźniewski

    2014-01-01

    Introduction : Secondary lymphedema affects approximately 40% of women treated for breast cancer and is recognized as a major problem associated with the therapy of malignant tumors. Consequently, new therapeutic methods are constantly being sought to effectively eliminate the condition. One of the new forms of edema management, especially in the initial stages of edematous development, is Kinesiology Taping (KT). Aim of the study : The aim of the study was to assess the effects of KT ap...

  12. Reducing the Cost of Proton Radiation Therapy: The Feasibility of a Streamlined Treatment Technique for Prostate Cancer

    OpenAIRE

    Newhauser, Wayne D.; Rui Zhang; Jones, Timothy G.; Annelise Giebeler; Taddei, Phillip J.; Robert D Stewart; Andrew Lee; Oleg Vassiliev

    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 standa...

  13. Overexpression of the novel senescence marker β-galactosidase (GLB1 in prostate cancer predicts reduced PSA recurrence.

    Directory of Open Access Journals (Sweden)

    Jennifer Wagner

    Full Text Available Senescence is a terminal growth arrest that functions as a tumor suppressor in aging and precancerous cells and is a response to selected anticancer compounds. Lysosomal-β-galactosidase (GLB1 hydrolyzes β-galactose from glycoconjugates and is the origin of senescence-associated β-gal activity (SA-β-gal. Using a new GLB1 antibody, senescence biology was investigated in prostate cancer (PCa tissues.In vitro characterization of GLB1 was determined in primary prostate epithelial cell cultures passaged to replicative senescence and in therapy-induced senescence in PCa lines using chemotherapeutic agents. FFPE tissue microarrays were subjected to immunofluorescent staining for GLB1, Ki67 and HP1γ and automated quantitative imaging initially using AQUA in exploratory samples and Vectra in a validation series.GLB1 expression accumulates in replicative and induced senescence and correlates with senescent morphology and P16 (CDKN2 expression. In tissue arrays, quantitative imaging detects increased GLB1 expression in high-grade prostatic intraepithelial neoplasia (HGPIN, known to contain senescent cells, and cancer compared to benign prostate tissues (p<0.01 and senescent cells contain low Ki67 and elevated HP1γ. Within primary tumors, elevated GLB1 associates with lower T stage (p=0.01, localized versus metastatic disease (p=0.0003 and improved PSA-free survival (p=0.03. Increased GLB1 stratifies better PSA-free survival in intermediate grade PCa (0.01. Tissues that elaborate higher GLB1 display increased uniformity of expression.Increased GLB1 is a valuable marker in formalin-fixed paraffin-embedded (FFPE tissues for the senescence-like phenotype and associates with improved cancer outcomes. This protein addresses a lack of senescence markers and should be applicable to study the biologic role of senescence in other cancers.

  14. Beef conjugated linoleic acid isomers reduce human cancer cell growth even when associated with other beef fatty acids

    OpenAIRE

    De La Torre, Anne; Debiton, Eric; Juaneda, Pierre; Durand, Denis; Chardigny, Jean-Michel; Barthomeuf, Chantal; Bauchart, Dominique; Gruffat, Dominique

    2006-01-01

    Although many data are available concerning anticarcinogenic effects of industrial conjugated linoleic acid (CLA), few studies have reported the antitumour properties of CLA mixtures originating from ruminant products. The aim of the present study was to investigate the in vitro antiproliferative effects of beef CLA mixtures on breast, lung, colon, melanoma and ovarian human cancer cell lines. For this purpose, four fatty acid (FA) extracts prepared from beef lipid and varying in their CLA co...

  15. Reduced expression of Toll-like receptor 4 inhibits human breast cancer cells proliferation and inflammatory cytokines secretion

    OpenAIRE

    Xie Xiaofang; Wen Huiyan; Zhou Xiaoni; Feng Ping; Zhou Huiqin; Yang Huan; Shen Haiying; Zhu Xueming

    2010-01-01

    Abstract Background Tumor cell expression of Toll-like receptors (TLRs) can promote inflammation and cell survival in the tumor microenvironment. Toll-like receptor 4 (TLR4) signaling in tumor cells can mediate tumor cell immune escape and tumor progression, and it is regarded as one of the mechanisms for chronic inflammation in tumorigenesis and progression. The expression of TLR4 in human breast cancer cell line MDA-MB-231 and its biological function in the development and progression of br...

  16. Analysis of Intensity-Modulated Radiation Therapy (IMRT, Proton and 3D Conformal Radiotherapy (3D-CRT for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients

    Directory of Open Access Journals (Sweden)

    Ted C. Ling

    2014-12-01

    Full Text Available Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT, proton and 3D conformal radiotherapy (3D-CRT with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.

  17. Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ling, Ted C.; Slater, Jerry M.; Nookala, Prashanth; Mifflin, Rachel; Grove, Roger; Ly, Anh M.; Patyal, Baldev; Slater, Jerry D.; Yang, Gary Y., E-mail: gyang@llu.edu [Department of Radiation Medicine, Loma Linda University Medical Center, 11234 Anderson Street, A875, Loma Linda, CA 92354 (United States)

    2014-12-05

    Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients.

  18. Kinesiology Taping reduces lymphedema of the upper extremity in women after breast cancer treatment: a pilot study

    Directory of Open Access Journals (Sweden)

    Iwona Malicka

    2014-09-01

    Full Text Available Introduction : Secondary lymphedema affects approximately 40% of women treated for breast cancer and is recognized as a major problem associated with the therapy of malignant tumors. Consequently, new therapeutic methods are constantly being sought to effectively eliminate the condition. One of the new forms of edema management, especially in the initial stages of edematous development, is Kinesiology Taping (KT. Aim of the study : The aim of the study was to assess the effects of KT applications on the extent of lymphedema of the upper extremity in women post cancer treatment. Material and methods: The study group consisted of 28 women after axillary lymphadenectomy due to breast cancer. All the patients were diagnosed with grade I secondary lymphedema. Kinesiology Taping was applied to a total of 14 randomly selected women. The remaining 14 patients constituted a control group. The extent of lymphedema was measured using a centimeter tape and Limb Volumes Professional 5.0 software. Results : A significant reduction in the extent of lymphedema (p = 0.0009 was achieved in the KT group between baseline and post-treatment assessments. No such reduction, however, was found in the control group (p = 0.36. Conclusions : Kinesiology Taping applications are an effective method of early-stage edema management. Kinesiology Taping may be a safe new therapeutic option in patients who are contraindicated for the use of other methods.

  19. Inhibition of system L (LAT1/CD98hc) reduces the growth of cultured human breast cancer cells.

    Science.gov (United States)

    Shennan, David B; Thomson, Jean

    2008-10-01

    It has been suggested that system L (LAT1/CD98hc) is up-regulated in cancer cells, including breast tumour cells, and is therefore a promising molecular target to inhibit or limit tumour cell growth. In view of this, we have examined the effect of BCH and other inhibitors of system L on the growth of MCF-7, ZR-75-1 and MDA-MB-231 cells. Treating cells with BCH markedly inhibited the metabolism of WST-1 in a dose-dependent fashion. Similarly, melphalan and D-leucine inhibited the growth of cultured breast cancer cells whereas MeAIB, an inhibitor of system A, was without effect. The effects of BCH and melphalan on cell growth were non-additive suggesting that both compounds were acting at a single locus. The results indicate that system L is required to maintain MCF-7, ZR-75-1 and MDA-MB-231 cell growth and support the notion that LAT1/CD98hc may be a suitable target to inhibit breast cancer progression. PMID:18813831

  20. Ganoderma lucidum Combined with the EGFR Tyrosine Kinase Inhibitor, Erlotinib Synergize to Reduce Inflammatory Breast Cancer Progression.

    Science.gov (United States)

    Suárez-Arroyo, Ivette J; Rios-Fuller, Tiffany J; Feliz-Mosquea, Yismeilin R; Lacourt-Ventura, Mercedes; Leal-Alviarez, Daniel J; Maldonado-Martinez, Gerónimo; Cubano, Luis A; Martínez-Montemayor, Michelle M

    2016-01-01

    The high incidence of resistance to Tyrosine Kinase Inhibitors (TKIs) targeted against EGFR and downstream pathways has increased the necessity to identify agents that may be combined with these therapies to provide a sustained response for breast cancer patients. Here, we investigate the therapeutic potential of Ganoderma lucidum extract (GLE) in breast cancer, focusing on the regulation of the EGFR signaling cascade when treated with the EGFR TKI, Erlotinib. SUM-149, or intrinsic Erlotinib resistant MDA-MB-231 cells, and a successfully developed Erlotinib resistant cell line, rSUM-149 were treated with increasing concentrations of Erlotinib, GLE, or their combination (Erlotinib/GLE) for 72h. Treatment effects were tested on cell viability, cell proliferation, cell migration and invasion. To determine tumor progression, severe combined immunodeficient mice were injected with SUM-149 cells and then treated with Erlotinib/GLE or Erlotinib for 13 weeks. We assessed the protein expression of ERK1/2 and AKT in in vitro and in vivo models. Our results show that GLE synergizes with Erlotinib to sensitize SUM-149 cells to drug treatment, and overcomes intrinsic and developed Erlotinib resistance. Also, Erlotinib/GLE decreases SUM-149 cell viability, proliferation, migration and invasion. GLE increases Erlotinib sensitivity by inactivating AKT and ERK signaling pathways in our models. We conclude that a combinatorial therapeutic approach may be the best way to increase prognosis in breast cancer patients with EGFR overexpressing tumors.

  1. Ganoderma lucidum Combined with the EGFR Tyrosine Kinase Inhibitor, Erlotinib Synergize to Reduce Inflammatory Breast Cancer Progression.

    Science.gov (United States)

    Suárez-Arroyo, Ivette J; Rios-Fuller, Tiffany J; Feliz-Mosquea, Yismeilin R; Lacourt-Ventura, Mercedes; Leal-Alviarez, Daniel J; Maldonado-Martinez, Gerónimo; Cubano, Luis A; Martínez-Montemayor, Michelle M

    2016-01-01

    The high incidence of resistance to Tyrosine Kinase Inhibitors (TKIs) targeted against EGFR and downstream pathways has increased the necessity to identify agents that may be combined with these therapies to provide a sustained response for breast cancer patients. Here, we investigate the therapeutic potential of Ganoderma lucidum extract (GLE) in breast cancer, focusing on the regulation of the EGFR signaling cascade when treated with the EGFR TKI, Erlotinib. SUM-149, or intrinsic Erlotinib resistant MDA-MB-231 cells, and a successfully developed Erlotinib resistant cell line, rSUM-149 were treated with increasing concentrations of Erlotinib, GLE, or their combination (Erlotinib/GLE) for 72h. Treatment effects were tested on cell viability, cell proliferation, cell migration and invasion. To determine tumor progression, severe combined immunodeficient mice were injected with SUM-149 cells and then treated with Erlotinib/GLE or Erlotinib for 13 weeks. We assessed the protein expression of ERK1/2 and AKT in in vitro and in vivo models. Our results show that GLE synergizes with Erlotinib to sensitize SUM-149 cells to drug treatment, and overcomes intrinsic and developed Erlotinib resistance. Also, Erlotinib/GLE decreases SUM-149 cell viability, proliferation, migration and invasion. GLE increases Erlotinib sensitivity by inactivating AKT and ERK signaling pathways in our models. We conclude that a combinatorial therapeutic approach may be the best way to increase prognosis in breast cancer patients with EGFR overexpressing tumors. PMID:26958085

  2. DBGC: A Database of Human Gastric Cancer

    OpenAIRE

    Chao Wang; Jun Zhang; Mingdeng Cai; Zhenggang Zhu; Wenjie Gu; Yingyan Yu; Xiaoyan Zhang

    2015-01-01

    The Database of Human Gastric Cancer (DBGC) is a comprehensive database that integrates various human gastric cancer-related data resources. Human gastric cancer-related transcriptomics projects, proteomics projects, mutations, biomarkers and drug-sensitive genes from different sources were collected and unified in this database. Moreover, epidemiological statistics of gastric cancer patients in China and clinicopathological information annotated with gastric cancer cases were also integrated...

  3. Reduced Risk of Human Lung Cancer by Selective Cyclooxygenase 2 (Cox-2 Blockade: Results of a Case Control Study

    Directory of Open Access Journals (Sweden)

    Randall E. Harris, Joanne Beebe-Donk, Galal A. Alshafie

    2007-01-01

    Full Text Available We conducted a case control study of selective cyclooxygenase-2 (COX-2 blocking agents and lung cancer. A total of 492 newly diagnosed lung cancer cases were ascertained during January 1, 2002 to September 30, 2004, at The Ohio State University Medical Center, Columbus, Ohio. All cases were confirmed by examination of the pathology report. Healthy population controls without cancer were ascertained during the same time period. Controls were frequency matched at a rate of 2:1 to the cases by age, gender, and county of residence. We collected information on type, frequency, and duration of use of selective COX-2 inhibitors (primarily celecoxib or rofecoxib and nonselective NSAIDs such as ibuprofen and aspirin. Estimates of odds ratios (OR were obtained with adjustment for cigarette smoking, age and other potential confounders using logistic regression analysis. Odds Ratios for selective COX-2 inhibitors were adjusted for past use of other NSAIDs. Use of any selective COX-2 inhibitor for more than one year produced a significant (60% reduction in the risk of lung cancer (OR=0.40, 95% CI=0.19-0.81. Observed risk reductions were consistent for men (OR=0.26, 95% CI=0.10-0.62 and women (OR=0.52, 95% CI=0.24-1.13 and for individual COX-2 inhibitors (OR=0.28, 95% CI=-0.12-0.67, for celecoxib and OR=0.55, 95% CI=0.19-1.56, for rofecoxib. Intake of ibuprofen or aspirin also produced significant risk reductions (OR=0.40, 95% CI=0.23-0.73 and OR=0.53, 95% CI=0.34-0.82, respectively, whereas acetaminophen, an analgesic with negligible COX-2 activity, had no effect on the risk (OR=1.36, 95% CI=0.53-3.37. This investigation demonstrates for the first time that selective COX-2 blocking agents have strong potential for the chemoprevention of human lung cancer.

  4. 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

  5. Study protocol of a randomized controlled trial comparing Mindfulness-Based Stress Reduction with treatment as usual in reducing psychological distress in patients with lung cancer and their partners: the MILON study

    NARCIS (Netherlands)

    Schellekens, M.P.J.; Hurk, D.G.M. van den; Prins, J.B.; Molema, J.; Donders, A.R.T.; Woertman, W.H.; Drift, M.A. van der; Speckens, A.E.M.

    2014-01-01

    BACKGROUND: Lung cancer is the leading cause of cancer death worldwide and characterized by a poor prognosis. It has a major impact on the psychological wellbeing of patients and their partners. Recently, it has been shown that Mindfulness-Based Stress Reduction (MBSR) is effective in reducing anxie

  6. Study protocol of a multicenter randomized controlled trial comparing the effectiveness of group and individual internet-based Mindfulness-Based Cognitive Therapy with treatment as usual in reducing psychological distress in cancer patients: the BeMind study

    NARCIS (Netherlands)

    Compen, F.R.; Bisseling, E.M.; Lee, M.L. Van der; Adang, E.M.M.; Donders, A.R.T.; Speckens, A.E.M.

    2015-01-01

    BACKGROUND: Mindfulness-based interventions have shown to reduce psychological distress in cancer patients. The accessibility of mindfulness-based interventions for cancer patients could be further improved by providing mindfulness using an individual internet-based format. The aim of this study is

  7. Systematic Analysis of Sex-Linked Molecular Alterations and Therapies in Cancer

    OpenAIRE

    Jonathan Ma; Sadhika Malladi; Beck, Andrew H.

    2016-01-01

    Though patient sex influences response to cancer treatments, little is known of the molecular causes, and cancer therapies are generally given irrespective of patient sex. We assessed transcriptomic differences in tumors from men and women spanning 17 cancer types, and we assessed differential expression between tumor and normal samples stratified by sex across 7 cancers. We used the LincsCloud platform to perform Connectivity Map analyses to link transcriptomic signatures identified in male ...

  8. Transcriptome Analysis of Enterococcus faecalis in Response to Alkaline Stress

    Directory of Open Access Journals (Sweden)

    Ran eshujun

    2015-08-01

    Full Text Available E. faecalis is the most commonly isolated species from endodontic failure root canals; its persistence in treated root canals has been attributed to its ability to resist high pH stress. The goal of this study was to characterize the E. faecalis transcriptome and to identify candidate genes for response and resistance to alkaline stress using Illumina HiSeq 2000 sequencing.We found that E. faecalis could survive and form biofilms in a pH 10 environment and that alkaline stress had a great impact on the transcription of many genes in the E. faecalis genome. The transcriptome sequencing results revealed that 613 genes were differentially expressed (DEGs for E. faecalis grown in pH 10 medium; 211 genes were found to be differentially up-regulated and 402 genes differentially down-regulated. Many of the down-regulated genes found are involved in cell energy production and metabolism and carbohydrate and amino acid metabolism, and the up-regulated genes are mostly related to nucleotide transport and metabolism. The results presented here reveal that cultivation of E. faecalis in alkaline stress has a profound impact on its transcriptome. The observed regulation of genes and pathways revealed that E. faecalis reduced its carbohydrate and amino acid metabolism and increased nucleotide synthesis to adapt and grow in alkaline stress. A number of the regulated genes may be useful candidates for the development of new therapeutic approaches for the treatment of E. faecalis infections.

  9. Metformin and Rapamycin Reduce Pancreatic Cancer Growth in Obese Prediabetic Mice by Distinct MicroRNA-Regulated Mechanisms

    OpenAIRE

    Cifarelli, Vincenza; Laura M. Lashinger; Devlin, Kaylyn L.; Dunlap, Sarah M; Huang, Jennifer; Kaaks, Rudolf; Pollak, Michael N.; Hursting, Stephen D.

    2015-01-01

    Metformin treatment is associated with a decreased risk and better prognosis of pancreatic cancer (PC) in patients with type 2 diabetes, but the mechanism of metformin’s PC growth inhibition in the context of a prediabetic state is unknown. We used a Panc02 pancreatic tumor cell transplant model in diet-induced obese (DIO) C57BL/6 mice to compare the effects of metformin and the direct mammalian target of rapamycin (mTOR) inhibitor rapamycin on PC growth, glucose regulation, mTOR pathway sign...

  10. 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.

  11. The olfactory transcriptomes of mice.

    Science.gov (United States)

    Ibarra-Soria, Ximena; Levitin, Maria O; Saraiva, Luis R; Logan, Darren W

    2014-09-01

    The olfactory (OR) and vomeronasal receptor (VR) repertoires are collectively encoded by 1700 genes and pseudogenes in the mouse genome. Most OR and VR genes were identified by comparative genomic techniques and therefore, in many of those cases, only their protein coding sequences are defined. Some also lack experimental support, due in part to the similarity between them and their monogenic, cell-specific expression in olfactory tissues. Here we use deep RNA sequencing, expression microarray and quantitative RT-PCR in both the vomeronasal organ and whole olfactory mucosa to quantify their full transcriptomes in multiple male and female mice. We find evidence of expression for all VR, and almost all OR genes that are annotated as functional in the reference genome, and use the data to generate over 1100 new, multi-exonic, significantly extended receptor gene annotations. We find that OR and VR genes are neither equally nor randomly expressed, but have reproducible distributions of abundance in both tissues. The olfactory transcriptomes are only minimally different between males and females, suggesting altered gene expression at the periphery is unlikely to underpin the striking sexual dimorphism in olfactory-mediated behavior. Finally, we present evidence that hundreds of novel, putatively protein-coding genes are expressed in these highly specialized olfactory tissues, and carry out a proof-of-principle validation. Taken together, these data provide a comprehensive, quantitative catalog of the genes that mediate olfactory perception and pheromone-evoked behavior at the periphery. PMID:25187969

  12. The olfactory transcriptomes of mice.

    Directory of Open Access Journals (Sweden)

    Ximena Ibarra-Soria

    2014-09-01

    Full Text Available The olfactory (OR and vomeronasal receptor (VR repertoires are collectively encoded by 1700 genes and pseudogenes in the mouse genome. Most OR and VR genes were identified by comparative genomic techniques and therefore, in many of those cases, only their protein coding sequences are defined. Some also lack experimental support, due in part to the similarity between them and their monogenic, cell-specific expression in olfactory tissues. Here we use deep RNA sequencing, expression microarray and quantitative RT-PCR in both the vomeronasal organ and whole olfactory mucosa to quantify their full transcriptomes in multiple male and female mice. We find evidence of expression for all VR, and almost all OR genes that are annotated as functional in the reference genome, and use the data to generate over 1100 new, multi-exonic, significantly extended receptor gene annotations. We find that OR and VR genes are neither equally nor randomly expressed, but have reproducible distributions of abundance in both tissues. The olfactory transcriptomes are only minimally different between males and females, suggesting altered gene expression at the periphery is unlikely to underpin the striking sexual dimorphism in olfactory-mediated behavior. Finally, we present evidence that hundreds of novel, putatively protein-coding genes are expressed in these highly specialized olfactory tissues, and carry out a proof-of-principle validation. Taken together, these data provide a comprehensive, quantitative catalog of the genes that mediate olfactory perception and pheromone-evoked behavior at the periphery.

  13. Matrine reduces proliferation of human lung cancer cells by inducing apoptosis and changing miRNA expression profiles.

    Science.gov (United States)

    Liu, Yong-Qi; Li, Yi; Qin, Jie; Wang, Qian; She, Ya-Li; Luo, Ya-Li; He, Jian-Xin; Li, Jing-Ya; Xie, Xiao-Dong

    2014-01-01

    Matrine, a main active component extracted from dry roots of Sophora flavecens , has been reported to exert antitumor effects on A549 human non-small lung cancer cells, but its mechanisms of action remain unclear. To determine effects of matrine on proliferation of A549 cells and assess possible mechanisms, MTT assays were employed to detect cytotoxicity, along with o flow cytometric analysis of DNA content of nuclei of cells following staining with propidium iodide to analyze cell cycle distribution. Western blotting was performed to determined expression levels of Bax, Bcl-2, VEGF and HDAC1, while a microarray was used to assessed changes of miRNA profiles. In the MTT assay, matrine suppressed growth of human lung cancer cell A549 in a dose- and time- dependent manner at doses of 0.25-2.5 mg/ml for 24h, 48h or 72h. Matrine induced cell cycle arrest in G0/G1 phase and decreased the G2/M phase, while down-regulating the expression of Bcl2 protein, leading to a reduction in the Bcl-2/Bax ratio. In addition, matrine down regulated the expression level of VEGF and HDAC1 of A549 cells. Microarray analysis demonstrated that matrine altered the expression level of miRNAs compared with untreated control A549 cells. In conclusion, matrine could inhibit proliferation of A549 cells, providing useful information for understanding anticancer mechanisms.

  14. Reducing Colorectal Cancer Incidence and Disparities: Performance and Outcomes of a Screening Colonoscopy Program in South Carolina

    Directory of Open Access Journals (Sweden)

    Sudha Xirasagar

    2014-01-01

    Full Text Available This study evaluated the efficiency, effectiveness, and racial disparities reduction potential of Screening Colonoscopies for People Everywhere in South Carolina (SCOPE SC, a state-funded program for indigent persons aged 50–64 years (45–64 years for African American (AA with a medical home in community health centers. Patients were referred to existing referral network providers, and the centers were compensated for patient navigation. Data on procedures and patient demographics were analyzed. Of 782 individuals recruited (71.2% AA, 85% (665 completed the procedure (71.1% AA. The adenoma detection rate was 27.8% (males 34.6% and females 25.1%, advanced neoplasm rate 7.7% (including 3 cancers, cecum intubation rate 98.9%, inadequate bowel preparation rate 7.9%, and adverse event rate 0.9%. All indicators met the national quality benchmarks. The adenoma rate of 26.0% among AAs aged 45–49 years was similar to that of older Whites and AAs. We found that patient navigation and a medical home setting resulted in a successful and high-quality screening program. The observed high adenoma rate among younger AAs calls for more research with larger cohorts to evaluate the appropriateness of the current screening guidelines for AAs, given that they suffer 47% higher colorectal cancer mortality than Whites.

  15. Reduced mrna expression level of corticotropin-releasing hormone-binding protein is associated with aggressive human kidney cancer

    International Nuclear Information System (INIS)

    Significance of Urocortin (Ucn or UcnI), Ucn2, Ucn3 and their receptors, Corticotropin Releasing Factor Receptor 1 and 2 (CRFR1 and CRFR2), and the binding protein, Corticotropin-Releasing Hormone-Binding Protein (CRHBP) in oncology is growing rapidly. The objective of our study was to assess the expression of the CRHBP mRNA and protein in renal cancer. Tumoral tissues of 78 patients with clear cell renal cell cancer and their corresponding normal tissues were analyzed using quantitative mRNA expression analysis for detection of mRNA expression level. Protein expression and tissue localization of CRHBP protein in renal specimens was evaluated using western blotting, immunohistochemistry and double immunofluorescence, respectively. We found an approx. 33 fold decrease of average CRHBP mRNA level in tumoral tissues compared to paired normal tissues (p<0.001). Diminished CRHBP mRNA expression was positively correlated with advanced, metastasized and higher stage of disease (p<0.001, p=0.026, p=0.028 respectively). CRHBP protein was detected in glomeruli and proximal tubules of normal kidney while none or weak immunopositivity was found in cc-RCC (p<0.001). The expression analysis of CRHBP shows that cc-RCC is characterized by a significant loss of CRHBP mRNA expression that furthermore is associated with a more aggressive state of tumors. Depletion of CRHBP proteins also indicate that the protein as part of the UCN system may be involved in renal carcinogenesis

  16. Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates

    NARCIS (Netherlands)

    B.K. Edwards (Brenda); E. Ward (Elizabeth); B.A. Kohler (Betsy); C. Eheman (Christie); A. Zauber (Ann); R.N. Anderson (Robert); A. Jemal (Ahmedin); M.J. Schymura (Maria); I. Lansdorp-Vogelaar (Iris); L.C. Seeff (Laura); M. van Ballegooijen (Marjolein); S.L. Goede (Luuk); L.A.G. Ries (Lynn)

    2010-01-01

    textabstractBACKGROUND. The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information regarding cancer occurrence and

  17. A novel Trojan-horse targeting strategy to reduce the non-specific uptake of nanocarriers by non-cancerous cells.

    Science.gov (United States)

    Shen, Zheyu; Wu, Hao; Yang, Sugeun; Ma, Xuehua; Li, Zihou; Tan, Mingqian; Wu, Aiguo

    2015-11-01

    One big challenge with active targeting of nanocarriers is non-specific binding between targeting molecules and non-target moieties expressed on non-cancerous cells, which leads to non-specific uptake of nanocarriers by non-cancerous cells. Here, we propose a novel Trojan-horse targeting strategy to hide or expose the targeting molecules of nanocarriers on-demand. The non-specific uptake by non-cancerous cells can be reduced because the targeting molecules are hidden in hydrophilic polymers. The nanocarriers are still actively targetable to cancer cells because the targeting molecules can be exposed on-demand at tumor regions. Typically, Fe3O4 nanocrystals (FN) as magnetic resonance imaging (MRI) contrast agents were encapsulated into albumin nanoparticles (AN), and then folic acid (FA) and pH-sensitive polymers (PP) were grafted onto the surface of AN-FN to construct PP-FA-AN-FN nanoparticles. Fourier transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), transmission electron microscope (TEM) and gel permeation chromatography (GPC) results confirm successful construction of PP-FA-AN-FN. According to difference of nanoparticle-cellular uptake between pH 7.4 and 5.5, the weight ratio of conjugated PP to nanoparticle FA-AN-FN (i.e. graft density) and the molecular weight of PP (i.e. graft length) are optimized to be 1.32 and 5.7 kDa, respectively. In vitro studies confirm that the PP can hide ligand FA to prevent it from binding to cells with FRα at pH 7.4 and shrink to expose FA at pH 5.5. In vivo studies demonstrate that our Trojan-horse targeting strategy can reduce the non-specific uptake of the PP-FA-AN-FN by non-cancerous cells. Therefore, our PP-FA-AN-FN might be used as an accurately targeted MRI contrast agent. PMID:26295434

  18. Characterization of the Asian Citrus Psyllid Transcriptome.

    Science.gov (United States)

    Reese, Justin; Christenson, Matthew K; Leng, Nan; Saha, Surya; Cantarel, Brandi; Lindeberg, Magdalen; Tamborindeguy, Cecilia; Maccarthy, Justin; Weaver, Daniel; Trease, Andrew J; Steven V, Ready; Davis, Vincent M; McCormick, Courtney; Haudenschild, Christian; Han, Shunsheng; Johnson, Shannon L; Shelby, Kent S; Huang, Hong; Bextine, Blake R; Shatters, Robert G; Hall, David G; Davis, Paul H; Hunter, Wayne B

    2014-01-01

    The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae) is a vector for the causative agents of Huanglongbing, which threatens citrus production worldwide. This study reports and discusses the first D. citri transcriptomes, encompassing the three main life stages of D. citri, egg, nymph and adult. The transcriptomes were annotated using Gene Ontology (GO) and insecticide-related genes within each life stage were identified to aid the development of future D. citri insecticides. Transcriptome assemblies and other sequence data are available for download at the International Asian Citrus Psyllid Genome Consortium website [http://psyllid.org/download] and at NCBI [http://www.ncbi.nlm.nih.gov/bioproject/29447]. PMID:24511328

  19. Characterization of the Asian Citrus Psyllid Transcriptome.

    Science.gov (United States)

    Reese, Justin; Christenson, Matthew K; Leng, Nan; Saha, Surya; Cantarel, Brandi; Lindeberg, Magdalen; Tamborindeguy, Cecilia; Maccarthy, Justin; Weaver, Daniel; Trease, Andrew J; Steven V, Ready; Davis, Vincent M; McCormick, Courtney; Haudenschild, Christian; Han, Shunsheng; Johnson, Shannon L; Shelby, Kent S; Huang, Hong; Bextine, Blake R; Shatters, Robert G; Hall, David G; Davis, Paul H; Hunter, Wayne B

    2014-01-01

    The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae) is a vector for the causative agents of Huanglongbing, which threatens citrus production worldwide. This study reports and discusses the first D. citri transcriptomes, encompassing the three main life stages of D. citri, egg, nymph and adult. The transcriptomes were annotated using Gene Ontology (GO) and insecticide-related genes within each life stage were identified to aid the development of future D. citri insecticides. Transcriptome assemblies and other sequence data are available for download at the International Asian Citrus Psyllid Genome Consortium website [http://psyllid.org/download] and at NCBI [http://www.ncbi.nlm.nih.gov/bioproject/29447].

  20. Adenovirus-mediated expression of UHRF1 reduces the radiosensitivity of cervical cancer HeLa cells to γ-irradiation

    Institute of Scientific and Technical Information of China (English)

    Xin-li LI; Qing-hui MENG; Sai-jun FAN

    2009-01-01

    Aim:An in vitro study was carried out to determine the effect of UHRF1 overexpression on radiosensitivity in human cervical cancer HeLa ceUs using adenovirus-mediated UHRF1 gene transfer (Ad5-UHRF1). Methods: Cell survival was evaluated using the clonogenic survival assay and the MTT assay; apoptosis and cell cycle distribution were monitored by flow cytometry. Protein levels were measured by Western blotting. Silencing XRCC4 expression was performed by transfection of small interfering RNA (siRNA).Results: Increased expression of UHRF1 by AdS-UHRF1 significantly reduced the radiosensitivity of HeLa cells. The UHRF1-mediated radioresistance was correlated with increased DNA repair capability and increased expression of the DNA damage repair protein, XRCC4. Knocking down XRCC4 expression in the cells using XRCC4 siRNA markedly reduced the UHRFl-mediated radioresistance. Conclusion: These results provide the first evidence for revealing a functional role of UHRF1 in human cervical cancer cells as a negative regulator of radiosensitivity.

  1. A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lips, Irene M., E-mail: i.m.lips@umcutrecht.nl [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Gils, Carla H. van [Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht (Netherlands); Kotte, Alexis N.T.J. [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Leerdam, Monique E. van [Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam (Netherlands); Franken, Stefan P.G.; Heide, Uulke A. van der; Vulpen, Marco van [Department of Radiation Oncology, University Medical Center Utrecht, Utrecht (Netherlands)

    2012-06-01

    Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondary outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.

  2. Metastasis is strongly reduced by the matrix metalloproteinase inhibitor Galardin in the MMTV-PymT transgenic breast cancer model

    DEFF Research Database (Denmark)

    Almholt, Kasper; Juncker-Jensen, Anna; Lærum, Ole Didrik;

    2008-01-01

    Matrix metalloproteinases (MMP) have several roles that influence cancer progression and dissemination. However, low molecular weight metalloproteinase inhibitors (MPI) have not yet been tested in transgenic/spontaneous metastasis models. We have tested Galardin/GM6001, a potent MPI that reacts...... collagen deposition, and increased MMP-2 activity. MMPs are known to have tumor-promoting and tumor-inhibitory effects, and several clinical trials of broad-spectrum MPIs have failed to show promising effects. The very potent antimetastatic effect of Galardin in the MMTV-PymT model does, however, show that...... it may be possible to find broad-spectrum MPIs with favorable inhibition profiles, or perhaps combinations of monospecific MPIs, for future clinical application....

  3. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Oorschot, Bregje van, E-mail: b.vanoorschot@amc.uva.nl [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hovingh, Suzanne E. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Moerland, Perry D. [Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Medema, Jan Paul; Stalpers, Lukas J.A. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Vrieling, Harry [Department of Toxicogenetics, Leiden University Medical Center, Leiden (Netherlands); Franken, Nicolaas A.P. [Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Molecular Medicine (CEMM), Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

  4. Willingness to participate in a parental training intervention to reduce neurocognitive late effects among Latino parents of childhood cancer survivors.

    Science.gov (United States)

    Dennis, Jessica M; Rosen, Roxanna; Patel, Sunita K

    2015-03-01

    The purpose of the study was to examine correlates of Spanish-speaking Latino parents' interest for participation in an educational intervention to improve learning and school success in children with cancer-related cognitive and behavioral late effects. Participants included 73 Latino caregivers of school-age children who are survivors of brain tumor or leukemia and at risk for cognitive late effects. The parents completed a battery of surveys relating to interest in and barriers to intervention participation, as well as measures of parental knowledge and beliefs and their children's cognitive functioning, and health-related quality of life. Results showed that the majority of parents expressed interest in participating in the proposed 8-week intervention, with over 90% indicating interest in learning more about improving grades, making learning more exciting, being a role model, and the impact of cancer on memory. The factors most strongly related to interest in intervention included lower maternal education as well as perceptions of greater child cognitive difficulties and lower health-related quality of life. The barriers most highly endorsed by the most parents were difficulty paying for gas, child care responsibility, and too much stress in other parts of life. Also highly endorsed as barriers were statements relating to the child's lack of interest and need for services (i.e., my child is doing fine). These findings are consistent with the Health Belief Model wherein decisions to engage in health-related behaviors are made by weighing the potential benefits relative to the costs and barriers. PMID:24792525

  5. Comparative transcriptomics in the Triticeae

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    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. Resistance to bleomycin in cancer cell lines is characterized by prolonged doubling time, reduced DNA damage and evasion of G2/M arrest and apoptosis.

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    Qi Wang

    Full Text Available BACKGROUND: To establish, characterize and elucidate potential mechanisms of acquired bleomycin (BLM resistance using human cancer cell lines. Seven BLM-resistant cell lines were established by exposure to escalating BLM concentrations over a period of 16-24 months. IC50 values and cell doubling times were quantified using a real time cytotoxicity assay. COMET and γ-H2AX assays, cell cycle analysis, and apoptosis assessment further investigated the mechanisms of BLM resistance in these cell lines. RESULTS: Compared with parental cell lines, real time cytotoxicity assays revealed 7 to 49 fold increases in IC50 and a mean doubling time increase of 147 % (range 64 %-352% in BLM-resistant sub-clones (p<0.05 for both. Higher maintenance BLM concentrations were associated with higher IC50 and increased doubling times (p<0.05. Significantly reduced DNA damage (COMET and γ-H2AX assays, G2/M arrest, and apoptosis (p<0.05 for each set of comparison following high-dose acute BLM exposure was observed in resistant sub-clones, compared with their BLM-sensitive parental counterparts. Three weeks of BLM-free culturing resulted in a partial return to BLM sensitivity in 3/7 BLM-resistant sub-clones (p<0.05. CONCLUSION: Bleomycin resistance may be associated with reduced DNA damage after bleomycin exposure, resulting in reduced G2/M arrest, and reduced apoptosis.

  7. Cytosine deaminase adenoviral vector and 5-fluorocytosine selectively reduce breast cancer cells 1 million-fold when they contaminate hematopoietic cells: a potential purging method for autologous transplantation.

    Science.gov (United States)

    Garcia-Sanchez, F; Pizzorno, G; Fu, S Q; Nanakorn, T; Krause, D S; Liang, J; Adams, E; Leffert, J J; Yin, L H; Cooperberg, M R; Hanania, E; Wang, W L; Won, J H; Peng, X Y; Cote, R; Brown, R; Burtness, B; Giles, R; Crystal, R; Deisseroth, A B

    1998-07-15

    48 hours. All of the BCC lines tested were shown to be sensitive to infection by adenoviral vectors when exposed to a recombinant adenoviral vector containing the reporter gene betagalactosidase (Ad.CMV-betagal). In contrast, less than 1% of the CD34-selected cells and their more immature subsets, such as the CD34+CD38- or CD34(+)CD33- subpopulations, were positive for infection by the Ad.CMV-betagal vector, as judged by fluorescence-activated cell sorting (FACS) analysis, when exposed to the adenoviral vector under conditions that did not commit the early hematopoietic precursor cells to maturation. When artificial mixtures of hematopoietic cells and BCCs were exposed for 90 minutes to the Ad.CMV-CD vector and to 5-FC for 10 days or more, a greater than 1 million fold reduction in the number of BCCs, as measured by colony-limiting dilution assays, was observed. To test if the conditions were damaging for the hematopoietic reconstituting cells, marrow cells collected from 5-FU-treated male donor mice were incubated with the cytosine deaminase adenoviral vector and then exposed to 5-FC either for 4 days in vitro before transplantation or for 14 days immediately after transplantation in vivo. There was no significant decrease in the reconstituting capability of the male marrow cells, as measured by their persistence in female irradiated recipients for up to 6 months after transplantation. These observations suggest that adenovirus-mediated gene transfer of the Escherichia coli cytosine deaminase gene followed by exposure to the nontoxic pro-drug 5-FC may be a potential strategy to selectively reduce the level of contaminating BCCs in collections of hematopoietic cells used for autografts in breast cancer patients.

  8. Characterization of the Asian Citrus Psyllid Transcriptome

    OpenAIRE

    Reese, Justin; Christenson, Matthew K.; Leng, Nan; Saha, Surya; Cantarel, Brandi; Lindeberg, Magdalen; Tamborindeguy, Cecilia; MacCarthy, Justin; Weaver, Daniel; Trease, Andrew J.; Ready, Steven V.; Davis, Vincent M.; McCormick, Courtney; Haudenschild, Christian; Han, Shunsheng

    2014-01-01

    The Asian citrus psyllid, Diaphorina citri Kuwayama (Hemiptera: Psyllidae) is a vector for the causative agents of Huanglongbing, which threatens citrus production worldwide. This study reports and discusses the first D. citri transcriptomes, encompassing the three main life stages of D. citri, egg, nymph and adult. The transcriptomes were annotated using Gene Ontology (GO) and insecticide-related genes within each life stage were identified to aid the development of future D. citri insectici...

  9. The effect-enhancing and toxicity-reducing activity of Hypericum japonicum Thunb. extract in murine liver cancer chemotherapy

    OpenAIRE

    ZHANG, HONG-BO; Lu, Ping; CAO, WEN-BO; Zhang, Zhen-Hua; MENG, XIANG-LEI

    2012-01-01

    Chinese herbs are potential sources of antitumor drugs with immunoregulatory activity and few adverse effects. In the present study, we investigated whether the Hypericum japonicum Thunb. (HJT) extract enhanced the efficacy of 5-fluorouracil (5-FU) treatment in murine liver tumor xenografts and reduced toxicity of chemotherapy in hepatoma H22-bearing mice. Tumor weight and inhibition rate, thymus and spleen indices, as well as white blood cell (WBC) count were calculated. The phagocytic funct...

  10. An efficient transcriptome analysis pipeline to accelerate venom peptide discovery and characterisation.

    Science.gov (United States)

    Prashanth, Jutty Rajan; Lewis, Richard J

    2015-12-01

    Transcriptome sequencing is now widely adopted as an efficient means to study the chemical diversity of venoms. To improve the efficiency of analysis of these large datasets, we have optimised an analysis pipeline for cone snail venom gland transcriptomes. The pipeline combines ConoSorter with sequence architecture-based elimination and similarity searching using BLAST to improve the accuracy of sequence identification and classification, while reducing requirements for manual intervention. As a proof-of-concept, we used this approach reanalysed three previously published cone snail transcriptomes from diverse dietary groups. Our pipeline method generated similar results to the published studies with significantly less manual intervention. We additionally found undiscovered sequences in the piscovorous Conus geographus and vermivorous Conus miles and identified sequences in incorrect superfamilies in the molluscivorus Conus marmoreus and C. geographus transcriptomes. Our results indicate that this method can improve toxin detection without extending analysis time. While this method was evaluated on cone snail transcriptomes it can be easily optimised to retrieve toxins from other venomous animals. PMID:26376071

  11. 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.

  12. Metaplastic breast carcinomas display genomic and transcriptomic heterogeneity [corrected]. .

    Science.gov (United States)

    Weigelt, Britta; Ng, Charlotte K Y; Shen, Ronglai; Popova, Tatiana; Schizas, Michail; Natrajan, Rachael; Mariani, Odette; Stern, Marc-Henri; Norton, Larry; Vincent-Salomon, Anne; Reis-Filho, Jorge S

    2015-03-01

    Metaplastic breast carcinoma is a rare and aggressive histologic type of breast cancer, preferentially displaying a triple-negative phenotype. We sought to define the transcriptomic heterogeneity of metaplastic breast cancers on the basis of current gene expression microarray-based classifiers, and to determine whether these tumors display gene copy number profiles consistent with those of BRCA1-associated breast cancers. Twenty-eight consecutive triple-negative metaplastic breast carcinomas were reviewed, and the metaplastic component present in each frozen specimen was defined (ie, spindle cell, squamous, chondroid metaplasia). RNA and DNA extracted from frozen sections with tumor cell content >60% were subjected to gene expression (Illumina HumanHT-12 v4) and copy number profiling (Affymetrix SNP 6.0), respectively. Using the best practice PAM50/claudin-low microarray-based classifier, all metaplastic breast carcinomas with spindle cell metaplasia were of claudin-low subtype, whereas those with squamous or chondroid metaplasia were preferentially of basal-like subtype. Triple-negative breast cancer subtyping using a dedicated website (http://cbc.mc.vanderbilt.edu/tnbc/) revealed that all metaplastic breast carcinomas with chondroid metaplasia were of mesenchymal-like subtype, spindle cell carcinomas preferentially of unstable or mesenchymal stem-like subtype, and those with squamous metaplasia were of multiple subtypes. None of the cases was classified as immunomodulatory or luminal androgen receptor subtype. Integrative clustering, combining gene expression and gene copy number data, revealed that metaplastic breast carcinomas with spindle cell and chondroid metaplasia were preferentially classified as of integrative clusters 4 and 9, respectively, whereas those with squamous metaplasia were classified into six different clusters. Eight of the 26 metaplastic breast cancers subjected to SNP6 analysis were classified as BRCA1-like. The diversity of histologic

  13. Transcriptome Alterations In X-Irradiated Human Gingiva Fibroblasts.

    Science.gov (United States)

    Weissmann, Robert; Kacprowski, Tim; Peper, Michel; Esche, Jennifer; Jensen, Lars R; van Diepen, Laura; Port, Matthias; Kuss, Andreas W; Scherthan, Harry

    2016-08-01

    Ionizing radiation is known to induce genomic lesions, such as DNA double strand breaks, whose repair can lead to mutations that can modulate cellular and organismal fate. Soon after radiation exposure, cells induce transcriptional changes and alterations of cell cycle programs to respond to the received DNA damage. Radiation-induced mutations occur through misrepair in a stochastic manner and increase the risk of developing cancers years after the incident, especially after high dose radiation exposures. Here, the authors analyzed the transcriptomic response of primary human gingival fibroblasts exposed to increasing doses of acute high dose-rate x rays. In the dataset obtained after 0.5 and 5 Gy x-ray exposures and two different repair intervals (0.5 h and 16 h), the authors discovered several radiation-induced fusion transcripts in conjunction with dose-dependent gene expression changes involving a total of 3,383 genes. Principal component analysis of repeated experiments revealed that the duration of the post-exposure repair intervals had a stronger impact than irradiation dose. Subsequent overrepresentation analyses showed a number of KEGG gene sets and WikiPathways, including pathways known to relate to radioresistance in fibroblasts (Wnt, integrin signaling). Moreover, a significant radiation-induced modulation of microRNA targets was detected. The data sets on IR-induced transcriptomic alterations in primary gingival fibroblasts will facilitate genomic comparisons in various genotoxic exposure scenarios.

  14. International network of cancer genome projects.

    OpenAIRE

    Aretz, Axel; Bernabé, Rosa R.; Eerola, Iiro; Hemsley, Fiona M.; Jennings, Jennifer L.; Kerr, David; Klatt, Peter; Kolar, Patrik; Lane, David P; Laplace, Frank; Nettekoven, Gerd; Remacle, Jacques; WATANABE, Koichi; Yuen, Matthew M. F.; Knoppers, Bartha M.

    2010-01-01

    The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeut...

  15. Hormone therapy with tamoxifen reduces plasma levels of NT-B-type natriuretic peptide but does not change ventricular ejection fraction after chemotherapy in women with breast cancer

    Directory of Open Access Journals (Sweden)

    F.B. Silva

    2015-02-01

    Full Text Available The objective of this study was to evaluate the effect of tamoxifen on the plasma concentration of NT-pro-B-type natriuretic peptide (NT-proBNP in women undergoing chemotherapy for breast cancer and to correlate changes in NT-proBNP with the left ventricular ejection fraction (LVEF. Over a period of 12 months, we followed 60 women with a diagnosis of breast cancer. The patients were separated into a group that received only chemotherapy (n=23, a group that received chemotherapy + tamoxifen (n=21, and a group that received only tamoxifen (n=16. Plasma levels of NT-proBNP were assessed at 0 (T0, 6 (T6, and 12 (T12 months of treatment, and echocardiography data were assessed at T0 and T12. Plasma NT-proBNP levels were increased in the chemotherapy-only group at T6 and T12, whereas elevated NT-proBNP levels were only found at T6 in the chemotherapy + tamoxifen group. At T12, the chemotherapy + tamoxifen group exhibited a significant reduction in the peptide to levels similar to the group that received tamoxifen alone. The chemotherapy-only group exhibited a significant decrease in LVEF at T12, whereas the chemotherapy + tamoxifen and tamoxifen-only groups maintained levels similar to those at the beginning of treatment. Treatment with tamoxifen for 6 months after chemotherapy significantly reduced the plasma levels of NT-proBNP and did not change LVEF in women with breast cancer.

  16. Selenium Nanoparticle-Enriched Lactobacillus Brevis Causes More Efficient Immune Responses In Vivo And Reduces The Liver Metastasis In Metastatic Form Of Mouse Breast Cancer

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    Mohammad Esfandyar

    2013-04-01

    Full Text Available Background and the purpose of the study:Selenium enriched Lactobacillus has been reported as an immunostimulatory agent which can be used to increase the life span of cancer bearing animals. Lactic acid bacteria can reduce selenium ions to elemental selenium nanoparticles (SeNPs and deposit them in intracellular spaces. In this strategy two known immunostimulators, lactic acid bacteria (LAB and SeNPs, are concomitantly administered for enhancing of immune responses in cancer bearing mice.Methods:Forty five female inbred BALB/c mice were divided into three groups of tests and control, each containing 15 mice. Test mice were orally administered with SeNP-enriched Lactobacillus brevis or Lactobacillus brevis alone for 3 weeks before tumor induction. After that the administration was followed in three cycles of seven days on/three days off. Control group received phosphate buffer saline (PBS at same condition. During the study the tumor growth was monitored using caliper method. At the end of study the spleen cell culture was carried out for both NK cytotoxicity assay and cytokines measurement. Delayed type hypersensitivity (DTH responses were also assayed after 72h of tumor antigen recall. Serum lactate dehydrogenase (LDH and alkaline phosphatase (ALP levels were measured, the livers of mice were removed and prepared for histopathological analysis.Results:High level of IFN-γ and IL-17 besides the significant raised in NK cytotoxicity and DTH responses were observed in SeNP-enriched L. brevis administered mice and the extended life span and decrease in the tumor metastasis to liver were also recorded in this group compared to the control mice or L.brevis alone administered mice.Conclusion:Our results suggested that the better prognosis could be achieved by oral administration of SeNP-enriched L. brevis in highly metastatic breast cancer mice model.

  17. Ultrasound-Assisted Thoracic Paravertebral Block Reduces Intraoperative Opioid Requirement and Improves Analgesia after Breast Cancer Surgery: A Randomized, Controlled, Single-Center Trial.

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    Lijian Pei

    Full Text Available The contribution of ultrasound-assisted thoracic paravertebral block to postoperative analgesia remains unclear. We compared the effect of a combination of ultrasound assisted-thoracic paravertebral block and propofol general anesthesia with opioid and sevoflurane general anesthesia on volatile anesthetic, propofol and opioid consumption, and postoperative pain in patients having breast cancer surgery.Patients undergoing breast cancer surgery were randomly assigned to ultrasound-assisted paravertebral block with propofol general anesthesia (PPA group, n = 121 or fentanyl with sevoflurane general anesthesia (GA group, n = 126. Volatile anesthetic, propofol and opioid consumption, and postoperative pain intensity were compared between the groups using noninferiority and superiority tests.Patients in the PPA group required less sevoflurane than those in the GA group (median [interquartile range] of 0 [0, 0] vs. 0.4 [0.3, 0.6] minimum alveolar concentration [MAC]-hours, less intraoperative fentanyl requirements (100 [50, 100] vs. 250 [200, 300]μg,, less intense postoperative pain (median visual analog scale score 2 [1, 3.5] vs. 3 [2, 4.5], but more propofol (median 529 [424, 672] vs. 100 [100, 130] mg. Noninferiority was detected for all four outcomes; one-tailed superiority tests for each outcome were highly significant at P<0.001 in the expected directions.The combination of propofol anesthesia with ultrasound-assisted paravertebral block reduces intraoperative volatile anesthetic and opioid requirements, and results in less post operative pain in patients undergoing breast cancer surgery.ClinicalTrial.gov NCT00418457.

  18. Regulator of G-Protein Signaling 5 Reduces HeyA8 Ovarian Cancer Cell Proliferation and Extends Survival in a Murine Tumor Model

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    Molly K. Altman

    2012-01-01

    Full Text Available The regulator of G-protein signaling 5 (RGS5 belongs to a family of GTPase activators that terminate signaling cascades initiated by extracellular mediators and G-protein-coupled receptors. RGS5 has an interesting dual biological role. One functional RGS5 role is as a pericyte biomarker influencing the switch to angiogenesis during malignant progression. Its other functional role is to promote apoptosis in hypoxic environments. We set out to clarify the extent to which RGS5 expression regulates tumor progression—whether it plays a pathogenic or protective role in ovarian tumor biology. We thus constructed an inducible gene expression system to achieve RGS5 expression in HeyA8-MDR ovarian cancer cells. Through this we observed that inducible RGS5 expression significantly reduces in vitro BrdU-positive HeyA8-MDR cells, although this did not correlate with a reduction in tumor volume observed using an in vivo mouse model of ovarian cancer. Interestingly, mice bearing RGS5-expressing tumors demonstrated an increase in survival compared with controls, which might be attributed to the vast regions of necrosis observed by pathological examination. Additionally, mice bearing RGS5-expressing tumors were less likely to have ulcerated tumors. Taken together, this data supports the idea that temporal expression and stabilization of RGS5 could be a valuable tactic within the context of a multicomponent approach for modulating tumor progression.

  19. Silencing of osteopontin promotes the radiosensitivity of breast cancer cells by reducing the expression of hypoxia inducible factor 1 and vascular endothelial growth factor

    Institute of Scientific and Technical Information of China (English)

    YANG Li; ZHAO Wei; ZUO Wen-shu; WEI Ling; SONG Xian-rang; WANG Xing-wu; ZHENG Gang; ZHENG Mei-zhu

    2012-01-01

    Background Osteopontin (OPN) is a secreted phosphoglycoprotein (SSP) that is overexpressed in a variety of tumors and was regarded as a molecular marker of tumors.In this study,we intended to demonstrate the role of OPN in human breast cancer cell line MDA-MB-231.Methods Recombinant plasmid expressing small interfering RNA (siRNA) specific to OPN mRNA was transfected into MDA-MB-231 cells to generate the stable transfected cell line MDA-MB-343,and the empty plasmid tansfected cells (MDA-MB-neg) or wildtype MDA-MB-231 cells were used as control cells respectively.Expression of OPN,hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) proteins was analyzed by Western blotting analysis.The radiosensitivity of cells was determined by detecting cell apoptosis,cell proliferation and cell senescence.Results HIF-1 and VEGF proteins in MDA-MB-343 cells were significantly downregulated upon the efficient knockdown of OPN expression under either hypoxia or normoxia environment.Moreover,expression of OPN protein was upregualted upon hypoxic culture.Stable OPN-silencing also decreased cell invasion,increased cell apoptosis and cell senescence,as well as reduced clonogenic survival,resulting in increase radiation tolerance.Conclusions Suppression of OPN gene expression can enhance radiosensitivity and affect cell apoptosis in breast cancer cells.OPN seems to be an attractive target for the improvement of radiotherapy.

  20. Decision aid on breast cancer screening reduces attendance rate: results of a large-scale, randomized, controlled study by the DECIDEO group.

    Science.gov (United States)

    Bourmaud, Aurelie; Soler-Michel, Patricia; Oriol, Mathieu; Regnier, Véronique; Tinquaut, Fabien; Nourissat, Alice; Bremond, Alain; Moumjid, Nora; Chauvin, Franck

    2016-03-15

    Controversies regarding the benefits of breast cancer screening programs have led to the promotion of new strategies taking into account individual preferences, such as decision aid. The aim of this study was to assess the impact of a decision aid leaflet on the participation of women invited to participate in a national breast cancer screening program. This Randomized, multicentre, controlled trial. Women aged 50 to 74 years, were randomly assigned to receive either a decision aid or the usual invitation letter. Primary outcome was the participation rate 12 months after the invitation. 16 000 women were randomized and 15 844 included in the modified intention-to-treat analysis. The participation rate in the intervention group was 40.25% (3174/7885 women) compared with 42.13% (3353/7959) in the control group (p = 0.02). Previous attendance for screening (RR = 6.24; [95%IC: 5.75-6.77]; p aid reduced the participation rate. The decision aid activate the decision making process of women toward non-attendance to screening. These results show the importance of promoting informed patient choices, especially when those choices cannot be anticipated.

  1. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi

    1973-09-01

    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  2. Investigation of HER2 expression in canine mammary tumors by antibody-based, transcriptomic and mass spectrometry analysis: is the dog a suitable animal model for human breast cancer?

    Science.gov (United States)

    Burrai, G P; Tanca, A; De Miglio, M R; Abbondio, M; Pisanu, S; Polinas, M; Pirino, S; Mohammed, S I; Uzzau, S; Addis, M F; Antuofermo, E

    2015-11-01

    Canine mammary tumors (CMTs) share many features with human breast cancer (HBC), specifically concerning cancer-related pathways. Although the human epidermal growth factor receptor 2 (HER2) plays a significant role as a therapeutic and prognostic biomarker in HBC, its relevance in the pathogenesis and prognosis of CMT is still controversial. The aim of this study was to investigate HER2 expression in canine mammary hyperplasic and neoplastic tissues as well as to evaluate the specificity of the most commonly used polyclonal anti HER2 antibody by multiple molecular approaches. HER2 protein and RNA expression were determined by immunohistochemistry (IHC) and by quantitative real-time (qRT) PCR. A strong cell membrane associated with non-specific cytoplasmic staining was observed in 22% of carcinomas by IHC. Adenomas and carcinomas exhibited a significantly higher HER2 mRNA expression when compared to normal mammary glands, although no significant difference between benign and malignant tumors was noticed by qRT-PCR. The IHC results suggest a lack of specificity of the FDA-approved antibody in CMT samples as further demonstrated by Western immunoblotting (WB) and reverse phase protein arrays (RPPA). Furthemore, HER2 was not detected by mass spectrometry (MS) in a protein-expressing carcinoma at the IHC investigation. This study highlights that caution needs to be used when trying to translate from human to veterinary medicine information concerning cancer-related biomarkers and pathways. Further investigations are necessary to carefully assess the diagnostic and biological role specifically exerted by HER2 in CMTs and the use of canine mammary tumors as a model of HER2 over-expressing breast cancer. PMID:26088453

  3. American Society of Clinical Oncology policy statement update: tobacco control--reducing cancer incidence and saving lives. 2003.

    Science.gov (United States)

    2003-07-15

    As an international medical society dedicated to cancer prevention, the American Society of Clinical Oncology (ASCO) advocates a fundamental reform of United States and international policy toward addictive tobacco products. ASCO's goal is the immediate reduction of tobacco use and ultimate achievement of a tobacco-free world. The centerpiece of ASCO's policy is the recommendation for an independent commission to study the tobacco problem in all of its dimensions: social, medical, legal, and economic (both domestically and globally). The commission membership should include broad-based representation and expertise on tobacco issues. In ASCO's view, tobacco control efforts to date have been less than successful because they are too fragmented and incremental, leaving many important issues unaddressed. A more comprehensive solution could flow from this study, including input from a variety of government agencies involved with public health, agriculture, First Amendment and other legal considerations, and international trade. The study, within defined time limits, should culminate in a report that outlines a strategy for achieving immediate reduction of tobacco use and ultimate achievement of a tobacco-free world, including explicit plans and a timetable for implementation. Although this comprehensive approach to tobacco control will take many years to implement even under the best of circumstances, there are certain measures that could be undertaken immediately with meaningful impact on tobacco usage. These include: Increasing efforts to discourage tobacco use, particularly among the young Raising federal excise taxes by at least $2 per pack and encouraging states to consider tobacco taxes as a first resort in revenue enhancement Ensuring that tobacco settlement funds be devoted only to health-related projects, including medical treatment, biomedical research, and tobacco prevention efforts Requiring disclosure of all ingredients in tobacco products Comprehensively

  4. Could Intermittent Energy Restriction and Intermittent Fasting Reduce Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence.

    Science.gov (United States)

    Harvie, Michelle N; Howell, Tony

    2016-07-01

    Animal studies and human observational data link energy restriction (ER) to reduced rates of carcinogenesis. Most of these studies have involved continuous energy restriction (CER), but there is increasing public and scientific interest in the potential health and anticancer effects of intermittent energy restriction (IER) or intermittent fasting (IF), which comprise periods of marked ER or total fasting interspersed with periods of normal eating. This review summarizes animal studies that assessed tumor rates with IER and IF compared with CER or ad libitum feed consumption. The relevance of these animal data to human cancer is also considered by summarizing available human studies of the effects of IER or IF compared with CER on cancer biomarkers in obese, overweight, and normal-weight subjects. IER regimens that include periods of ER alternating with ad libitum feed consumption for 1, 2, or 3 wk have been reported to be superior to CER in reducing tumor rates in most spontaneous mice tumor models. Limited human data from short-term studies (≤6 mo) in overweight and obese subjects have shown that IER can lead to greater improvements in insulin sensitivity (homeostasis model assessment) than can CER, with comparable reductions in adipokines and inflammatory markers and minor changes in the insulin-like growth factor axis. There are currently no data comparing IER or IF with CER in normal-weight subjects. The benefits of IER in these short-term trials are of interest, but not sufficient evidence to recommend the use of IER above CER. Longer-term human studies of adherence to and efficacy and safety of IER are required in obese and overweight subjects, as well as normal-weight subjects. PMID:27422504

  5. MicroRNA-125a reduces proliferation and invasion of oral squamous cell carcinoma cells by targeting estrogen-related receptor α: implications for cancer therapeutics.

    Science.gov (United States)

    Tiwari, Ankana; Shivananda, Swamy; Gopinath, Kodaganur S; Kumar, Arun

    2014-11-14

    Estrogen-related receptor α (ESRRA) functions as a transcription factor and regulates the expression of several genes, such as WNT11 and OPN. Up-regulation of ESRRA has been reported in several cancers. However, the mechanism underlying its up-regulation is unclear. Furthermore, the reports regarding the role and regulation of ESRRA in oral squamous cell carcinoma (OSCC) are completely lacking. Here, we show that tumor suppressor miR-125a directly binds to the 3'UTR of ESRRA and represses its expression. Overexpression of miR-125a in OSCC cells drastically reduced the level of ESRRA, decreased cell proliferation, and increased apoptosis. Conversely, the delivery of an miR-125a inhibitor to these cells drastically increased the level of ESRRA, increased cell proliferation, and decreased apoptosis. miR-125a-mediated down-regulation of ESRRA impaired anchorage-independent colony formation and invasion of OSCC cells. Reduced cell proliferation and increased apoptosis of OSCC cells were dependent on the presence of the 3'UTR in ESRRA. The delivery of an miR-125a mimic to OSCC cells resulted in marked regression of xenografts in nude mice, whereas the delivery of an miR-125a inhibitor to OSCC cells resulted in a significant increase of xenografts and abrogated the tumor suppressor function of miR-125a. We observed an inverse correlation between the expression levels of miR-125a and ESRRA in OSCC samples. In summary, up-regulation of ESRRA due to down-regulation of miR-125a is not only a novel mechanism for its up-regulation in OSCC, but decreasing the level of ESRRA by using a synthetic miR-125a mimic may have an important role in therapeutic intervention of OSCC and other cancers.

  6. Transcriptome profiling of mice testes following low dose irradiation

    DEFF Research Database (Denmark)

    Belling, Kirstine C.; Tanaka, Masami; Dalgaard, Marlene Danner;

    2013-01-01

    cell types of the adult testis. We observed large expression changes in the somatic cell profile, which mainly could be attributed to changes in cellularity, but hyperplasia of Leydig cells may also play a role. We speculate that the possible hyperplasia may be caused by lower testosterone production......ABSTRACT: BACKGROUND: Radiotherapy is used routinely to treat testicular cancer. Testicular cells vary in radio-sensitivity and the aim of this study was to investigate cellular and molecular changes caused by low dose irradiation of mice testis and to identify transcripts from different cell types...... in the adult testis. METHODS: Transcriptome profiling was performed on total RNA from testes sampled at various time points (n = 17) after 1 Gy of irradiation. Transcripts displaying large overall expression changes during the time series, but small expression changes between neighbouring time points were...

  7. Probabilistic analysis of the human transcriptome with side information

    CERN Document Server

    Lahti, Leo

    2011-01-01

    Understanding functional organization of genetic information is a major challenge in modern biology. Following the initial publication of the human genome sequence in 2001, advances in high-throughput measurement technologies and efficient sharing of research material through community databases have opened up new views to the study of living organisms and the structure of life. In this thesis, novel computational strategies have been developed to investigate a key functional layer of genetic information, the human transcriptome, which regulates the function of living cells through protein synthesis. The key contributions of the thesis are general exploratory tools for high-throughput data analysis that have provided new insights to cell-biological networks, cancer mechanisms and other aspects of genome function. A central challenge in functional genomics is that high-dimensional genomic observations are associated with high levels of complex and largely unknown sources of variation. By combining statistical ...

  8. Superiority of Minimally Invasive Oesophagectomy in Reducing In-Hospital Mortality of Patients with Resectable Oesophageal Cancer: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Can Zhou

    Full Text Available Compared with open oesophagectomy (OE, minimally invasive oesophagectomy (MIO proves to have benefits in reducing the risk of pulmonary complications for patients with resectable oesophageal cancer. However, it is unknown whether MIO has superiority in reducing the occurrence of in-hospital mortality (IHM.The objective of this meta-analysis was to explore the effect of MIO vs. OE on the occurrence of in-hospital mortality (IHM.Sources such as Medline (through December 31, 2014, Embase (through December 31, 2014, Wiley Online Library (through December 31, 2014, and the Cochrane Library (through December 31, 2014 were searched.Data of randomized and non-randomized clinical trials related to MIO versus OE were included.Eligible studies were those that reported patients who underwent MIO procedure. The control group included patients undergoing conventional OE.Fixed or random -effects models were used to calculate summary odds ratios (ORs or relative risks (RRs for quantification of associations. Heterogeneity among studies was evaluated by using Cochran's Q and I2 statistics.A total of 48 studies involving 14,311 cases of resectable oesophageal cancer were included in the meta-analysis. Compared to patients undergoing OE, patients undergoing MIO had statistically reduced occurrence of IHM (OR=0.69, 95%CI =0.55 -0.86. Patients undergoing MIO also had significantly reduced incidence of pulmonary complications (PCs (RR=0.73, 95%CI = 0.63-0.86, pulmonary embolism (PE (OR=0.71, 95%CI= 0.51-0.99 and arrhythmia (OR=0.79, 95%CI = 0.68-0.92. Non-significant reductions were observed among the included studies in the occurrence of anastomotic leak (AL (OR=0.93, 95%CI =0.78-1.11, or Gastric Tip Necrosis (GTN (OR=0.89, 95%CI =0.54-1.49.Most of the included studies were non-randomized case-control studies, with a diversity of study designs, demographics of participants and surgical intervention.Minimally invasive oesophagectomy (MIO has superiority over open

  9. Whole genome and transcriptome sequencing of a B3 thymoma.

    Directory of Open Access Journals (Sweden)

    Iacopo Petrini

    Full Text Available Molecular pathology of thymomas is poorly understood. Genomic aberrations are frequently identified in tumors but no extensive sequencing has been reported in thymomas. Here we present the first comprehensive view of a B3 thymoma at whole genome and transcriptome levels. A 55-year-old Caucasian female underwent complete resection of a stage IVA B3 thymoma. RNA and DNA were extracted from a snap frozen tumor sample with a fraction of cancer cells over 80%. We performed array comparative genomic hybridization using Agilent platform, transcriptome sequencing using HiSeq 2000 (Illumina and whole genome sequencing using Complete Genomics Inc platform. Whole genome sequencing determined, in tumor and normal, the sequence of both alleles in more than 95% of the reference genome (NCBI Build 37. Copy number (CN aberrations were comparable with those previously described for B3 thymomas, with CN gain of chromosome 1q, 5, 7 and X and CN loss of 3p, 6, 11q42.2-qter and q13. One translocation t(11;X was identified by whole genome sequencing and confirmed by PCR and Sanger sequencing. Ten single nucleotide variations (SNVs and 2 insertion/deletions (INDELs were identified; these mutations resulted in non-synonymous amino acid changes or affected splicing sites. The lack of common cancer-associated mutations in this patient suggests that thymomas may evolve through mechanisms distinctive from other tumor types, and supports the rationale for additional high-throughput sequencing screens to better understand the somatic genetic architecture of thymoma.

  10. Transcriptome and microRNome of Theileria annulata Host Cells

    KAUST Repository

    Rchiad, Zineb

    2016-06-01

    Tropical Theileriosis is a parasitic disease of calves with a profound economic impact caused by Theileria annulata, an apicomplexan parasite of the genus Theileria. Transmitted by Hyalomma ticks, T. annulata infects and transforms bovine lymphocytes and macrophages into a cancer-like phenotype characterized by all six hallmarks of cancer. In the current study we investigate the transcriptional landscape of T. annulata-infected lymphocytes to define genes and miRNAs regulated by host cell transformation using next generation sequencing. We also define genes and miRNAs differentially expressed as a result of the attenuation of a T.annulata-infected macrophage cell line used as a vaccine. By comparing the transcriptional landscape of one attenuated and two transformed cell lines we identify four genes that we propose as key factors in transformation and virulence of the T. annulata host cells. We also identify miR- 126-5p as a key regulator of infected cells proliferation, adhesion, survival and invasiveness. In addition to the host cell trascriptome we studied T. annulata transcriptome and identified the role of ROS and TGF-β2 in controlling parasite gene expression. Moreover, we have used the deep parasite ssRNA-seq data to refine the available T. annulata annotation. Taken together, this study provides the full list of host cell’s genes and miRNAs transcriptionally perturbed after infection with T. annulata and after attenuation and describes genes and miRNAs never identified before as players in this type of host cell transformation. Moreover, this study provides the first database for the transcriptome of T. annulata and its host cells using next generation sequencing.

  11. [Transcriptome analysis of Dunaliella viridis].

    Science.gov (United States)

    Zhu, Shuaiqi; Gong, Yifu; Hang, Yuqing; Liu, Hao; Wang, Heyu

    2015-08-01

    In order to understand the gene information, function, haloduric pathway (glycerolipid metabolism) and related key genes for Dunaliella viridis, we used Illumina HiSeqTM 2000 high-throughput sequencing technology to sequence its transcriptome. Trinity soft was used to assemble the data to form transcripts. Based on the Clusters of Orthologous Groups (COG), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG ) databases, we carried out functional annotation and classification, pathway annotation, and the opening reading fragment (ORF) sequence prediction of transcripts. The key genes in the glycerolipid metabolism were analyzed. The results suggested that 81,593 transcripts were found, and 77,117 ORF sequences were predicted, accounting for 94.50% of all transcripts. COG classification results showed that 16,569 transcripts were assigned to 24 categories. GO classification annotated 76,436 transcripts. The number of transcripts for biologcial processes was 30,678, accounting for 40.14% of all transcripts. KEGG pathway analysis showed that 26,428 transcripts were annotated to 317 pathways, and 131 pathways were related to metabolism, accounting for 41.32% of all annotated pathways. Only one transcript was annotated as coding the key enzyme dihydroxyacetone kinase involved in the glycerolipid pathway. This enzyme could be related to glycerol biosynthesis under salt stress. This study further improved the gene information and laid the foundation of metabolic pathway research for Dunaliella viridis. PMID:26266786

  12. Investigating evolutionary perspective of carcinogenesis with single-cell transcriptome analysis

    Institute of Scientific and Technical Information of China (English)

    Xi Zhang; Cheng Zhang; Zhongjun Li; Jiangjian Zhong; Leslie P. Weiner; Jiang F. Zhong

    2013-01-01

    We developed phase-switch microfluidic devices for molecular profiling of a large number of single cells. Whole genome microarrays and RNA-sequencing are commonly used to determine the expression levels of genes in cell lysates (a physical mix of millions of cells) for inferring gene functions. However, cellular heterogeneity becomes an inherent noise in the measurement of gene expression. The unique molecular characteristics of individual cells, as well as the temporal and quantitative information of gene expression in cells, are lost when averaged among all cells in cell lysates. Our single-cell technology overcomes this limitation and enables us to obtain a large number of single-cell transcriptomes from a population of cells. A collection of single-cell molecular profiles allows us to study carcinogenesis from an evolutionary perspective by treating cancer as a diverse population of cells with abnormal molecular characteristics. Because a cancer cellpopulation contains cells at various stages of development toward drug resistance, clustering similar single-cell molecular profiles could reveal how drug-resistant sub-clones evolve during cancer treatment. Here, we discuss how single-celltranscriptome analysis technology could enable the study of carcinogenesis from an evolutionary perspective and the development of drug-resistance in leukemia. The single-cell transcriptome analysis reported here could have a direct and significant impact on current cancer treatments and future personalized cancer therapies.

  13. Reducing the Social Gradient in Uptake of the NHS Colorectal Cancer Screening Programme Using a Narrative-Based Information Leaflet: A Cluster-Randomised Trial

    Directory of Open Access Journals (Sweden)

    Lesley M. McGregor

    2016-01-01

    Full Text Available Objective. To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC screening programme on reducing socioeconomic inequalities in uptake. Participants. 150,417 adults (59–74 years routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt in March 2013. Design. A cluster randomised controlled trial (ISRCTN74121020 to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI + N. Between group comparisons were made for uptake overall and across socioeconomic status (SES. Results. Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI + N: 56.7%; odds ratio = 0.93; 95% confidence interval: 0.81–1.06; p=0.27. There was no interaction between group and SES quintile (p=0.44. Conclusions. Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace, existing information may have limited the true value of an evidence-based intervention on behaviour.

  14. Reducing the Social Gradient in Uptake of the NHS Colorectal Cancer Screening Programme Using a Narrative-Based Information Leaflet: A Cluster-Randomised Trial.

    Science.gov (United States)

    McGregor, Lesley M; von Wagner, Christian; Atkin, Wendy; Kralj-Hans, Ines; Halloran, Stephen P; Handley, Graham; Logan, Richard F; Rainbow, Sandra; Smith, Steve; Snowball, Julia; Thomas, Mary C; Smith, Samuel G; Vart, Gemma; Howe, Rosemary; Counsell, Nicholas; Hackshaw, Allan; Morris, Stephen; Duffy, Stephen W; Raine, Rosalind; Wardle, Jane

    2016-01-01

    Objective. To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC) screening programme on reducing socioeconomic inequalities in uptake. Participants. 150,417 adults (59-74 years) routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt) in March 2013. Design. A cluster randomised controlled trial (ISRCTN74121020) to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI) and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI + N). Between group comparisons were made for uptake overall and across socioeconomic status (SES). Results. Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI + N: 56.7%; odds ratio = 0.93; 95% confidence interval: 0.81-1.06; p = 0.27). There was no interaction between group and SES quintile (p = 0.44). Conclusions. Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace, existing information may have limited the true value of an evidence-based intervention on behaviour. PMID:27069473

  15. Reducing the Social Gradient in Uptake of the NHS Colorectal Cancer Screening Programme Using a Narrative-Based Information Leaflet: A Cluster-Randomised Trial.

    Science.gov (United States)

    McGregor, Lesley M; von Wagner, Christian; Atkin, Wendy; Kralj-Hans, Ines; Halloran, Stephen P; Handley, Graham; Logan, Richard F; Rainbow, Sandra; Smith, Steve; Snowball, Julia; Thomas, Mary C; Smith, Samuel G; Vart, Gemma; Howe, Rosemary; Counsell, Nicholas; Hackshaw, Allan; Morris, Stephen; Duffy, Stephen W; Raine, Rosalind; Wardle, Jane

    2016-01-01

    Objective. To test the effectiveness of adding a narrative leaflet to the current information material delivered by the NHS English colorectal cancer (CRC) screening programme on reducing socioeconomic inequalities in uptake. Participants. 150,417 adults (59-74 years) routinely invited to complete the guaiac Faecal Occult Blood test (gFOBt) in March 2013. Design. A cluster randomised controlled trial (ISRCTN74121020) to compare uptake between two arms. The control arm received the standard NHS CRC screening information material (SI) and the intervention arm received the standard information plus a supplementary narrative leaflet, which had previously been shown to increase screening intentions (SI + N). Between group comparisons were made for uptake overall and across socioeconomic status (SES). Results. Uptake was 57.7% and did not differ significantly between the two trial arms (SI: 58.5%; SI + N: 56.7%; odds ratio = 0.93; 95% confidence interval: 0.81-1.06; p = 0.27). There was no interaction between group and SES quintile (p = 0.44). Conclusions. Adding a narrative leaflet to existing information materials does not reduce the SES gradient in uptake. Despite the benefits of using a pragmatic trial design, the need to add to, rather than replace, existing information may have limited the true value of an evidence-based intervention on behaviour.

  16. Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis.

    Science.gov (United States)

    Konishi, Hiroaki; Fujiya, Mikihiro; Tanaka, Hiroki; Ueno, Nobuhiro; Moriichi, Kentaro; Sasajima, Junpei; Ikuta, Katsuya; Akutsu, Hiroaki; Tanabe, Hiroki; Kohgo, Yutaka

    2016-01-01

    Previous reports have suggested that some probiotics inhibit tumorigenesis and cancer progression. However, the molecules involved have not yet been identified. Here, we show that the culture supernatant of Lactobacillus casei ATCC334 has a strong tumour-suppressive effect on colon cancer cells. Using mass spectrometry, we identify ferrichrome as a tumour-suppressive molecule produced by L. casei ATCC334. The tumour-suppressive effect of ferrichrome is greater than that of cisplatin and 5-fluorouracil, and ferrichrome has less of an effect on non-cancerous intestinal cells than either of those agents. A transcriptome analysis reveals that ferrichrome treatment induces apoptosis, which is mediated by the activation of c-jun N-terminal kinase (JNK). Western blotting indicates that the induction of apoptosis by ferrichrome is reduced by the inhibition of the JNK signalling pathway. This we demonstrate that probiotic-derived ferrichrome exerts a tumour-suppressive effect via the JNK signalling pathway. PMID:27507542

  17. EGFR-TK inhibition before radiotherapy reduces tumour volume but does not improve local control: Differential response of cancer stem cells and nontumourigenic cells?

    International Nuclear Information System (INIS)

    Background and purpose: Waiting times before radiotherapy may reduce tumour control probability due to proliferation of tumour cells. The aim of the experiment was to test whether the growth inhibiting effect of epidermal growth factor receptor (EGFR)-inhibitors after surgery or tumour transplantation results in a lower tumour mass at time of irradiation and can thereby improve local tumour control. Materials and methods: The EGFR-tyrosine kinase inhibitor BIBX1382BS was applied over 14 days starting from microscopically non-in-sano-resection of FaDu tumours or from tumour transplantation, followed by irradiation (5f/5d). Endpoint was local tumour control. In addition, vital tumour areas, pimonidazole hypoxic fraction, BrdU labelling index, and colony forming ability in vitro were tested in control tumours and after BIBX1382BS treatment (starting from transplantation). Results: The tumour volume at start of irradiation was significantly lower in the BIBX1382BS treated tumours as compared to the control groups by factors of 11 (post-surgery setting) and 2.7 (transplantation setting). However, the reduced volume did not translate into improved local control after irradiation. The TCD50 values after surgery were 25.4 Gy [95% CI 18; 33 Gy] in the control group and 30.5 Gy [24; 37] in the BIBX1382BS group (p = 0.25). Treatment after transplantation resulted in TCD50 values of 41.1 Gy [35; 47] in the control group and 41.1 Gy [33; 49] in the BIBX1382BS group (p = 1). While the proportion of S-phase cells decreased after BIBX1382BS treatment, no differences were observed between the pimonidazole hypoxic fractions and in vitro colony forming ability. Conclusions: EGFR-TK inhibition with BIBX1382BS over 14 days between macroscopically complete tumour resection or tumour transplantation and start of radiotherapy significantly reduced tumour volume but did not improve local tumour control. One possible explanation is that the EGFR-TK inhibitor has a higher activity in

  18. Perspectives on the use of transcriptomics to advance biofuels

    Directory of Open Access Journals (Sweden)

    Siseon Lee

    2015-11-01

    Full Text Available As a field within the energy research sector, bioenergy is continuously expanding. Although much has been achieved and the yields of both ethanol and butanol have been improved, many avenues of research to further increase these yields still remain. This review covers current research related with transcriptomics and the application of this high-throughput analytical tool to engineer both microbes and plants with the penultimate goal being better biofuel production and yields. The initial focus is given to the responses of fermentative microbes during the fermentative production of acids, such as butyric acid, and solvents, including ethanol and butanol. As plants offer the greatest natural renewable source of fermentable sugars within the form of lignocellulose, the second focus area is the transcriptional responses of microbes when exposed to plant hydrolysates and lignin-related compounds. This is of particular importance as the acid/base hydrolysis methods commonly employed to make the plant-based cellulose available for enzymatic hydrolysis to sugars also generates significant amounts of lignin-derivatives that are inhibitory to fermentative bacteria and microbes. The article then transitions to transcriptional analyses of lignin-degrading organisms, such as Phanerochaete chrysosporium, as an alternative to acid/base hydrolysis. The final portion of this article will discuss recent transcriptome analyses of plants and, in particular, the genes involved in lignin production. The rationale behind these studies is to eventually reduce the lignin content present within these plants and, consequently, the amount of inhibitors generated during the acid/base hydrolysis of the lignocelluloses. All four of these topics represent key areas where transcriptomic research is currently being conducted to identify microbial genes and their responses to products and inhibitors as well as those related with lignin degradation/formation.

  19. Construction of coffee transcriptome networks based on gene annotation semantics.

    Science.gov (United States)

    Castillo, Luis F; Galeano, Narmer; Isaza, Gustavo A; Gaitán, Alvaro

    2012-07-24

    Gene annotation is a process that encompasses multiple approaches on the analysis of nucleic acids or protein sequences in order to assign structural and functional characteristics to gene models. When thousands of gene models are being described in an organism genome, construction and visualization of gene networks impose novel challenges in the understanding of complex expression patterns and the generation of new knowledge in genomics research. In order to take advantage of accumulated text data after conventional gene sequence analysis, this work applied semantics in combination with visualization tools to build transcriptome networks from a set of coffee gene annotations. A set of selected coffee transcriptome sequences, chosen by the quality of the sequence comparison reported by Basic Local Alignment Search Tool (BLAST) and Interproscan, were filtered out by coverage, identity, length of the query, and e-values. Meanwhile, term descriptors for molecular biology and biochemistry were obtained along the Wordnet dictionary in order to construct a Resource Description Framework (RDF) using Ruby scripts and Methontology to find associations between concepts. Relationships between sequence annotations and semantic concepts were graphically represented through a total of 6845 oriented vectors, which were reduced to 745 non-redundant associations. A large gene network connecting transcripts by way of relational concepts was created where detailed connections remain to be validated for biological significance based on current biochemical and genetics frameworks. Besides reusing text information in the generation of gene connections and for data mining purposes, this tool development opens the possibility to visualize complex and abundant transcriptome data, and triggers the formulation of new hypotheses in metabolic pathways analysis.

  20. Optimization of de novo short read assembly of seabuckthorn (Hippophae rhamnoides L. transcriptome.

    Directory of Open Access Journals (Sweden)

    Rajesh Ghangal

    Full Text Available Seabuckthorn (Hippophaerhamnoides L. is known for its medicinal, nutritional and environmental importance since ancient times. However, very limited efforts have been made to characterize the genome and transcriptome of this wonder plant. Here, we report the use of next generation massive parallel sequencing technology (Illumina platform and de novo assembly to gain a comprehensive view of the seabuckthorn transcriptome. We assembled 86,253,874 high quality short reads using six assembly tools. At our hand, assembly of non-redundant short reads following a two-step procedure was found to be the best considering various assembly quality parameters. Initially, ABySS tool was used following an additive k-mer approach. The assembled transcripts were subsequently subjected to TGICL suite. Finally, de novo short read assembly yielded 88,297 transcripts (> 100 bp, representing about 53 Mb of seabuckthorn transcriptome. The average length of transcripts was 610 bp, N50 length 1198 BP and 91% of the short reads uniquely mapped back to seabuckthorn transcriptome. A total of 41,340 (46.8% transcripts showed significant similarity with sequences present in nr protein databases of NCBI (E-value < 1E-06. We also screened the assembled transcripts for the presence of transcription factors and simple sequence repeats. Our strategy involving the use of short read assembler (ABySS followed by TGICL will be useful for the researchers working with a non-model organism's transcriptome in terms of saving time and reducing complexity in data management. The seabuckthorn transcriptome data generated here provide a valuable resource for gene discovery and development of functional molecular markers.

  1. Comprehensive evaluation of AmpliSeq transcriptome, a novel targeted whole transcriptome RNA sequencing methodology for global gene expression analysis

    OpenAIRE

    Li, Wenli; Turner, Amy; Aggarwal, Praful; Matter, Andrea; Storvick, Erin; Donna K Arnett; Broeckel, Ulrich

    2015-01-01

    Background Whole transcriptome sequencing (RNA-seq) represents a powerful approach for whole transcriptome gene expression analysis. However, RNA-seq carries a few limitations, e.g., the requirement of a significant amount of input RNA and complications led by non-specific mapping of short reads. The Ion AmpliSeq™ Transcriptome Human Gene Expression Kit (AmpliSeq) was recently introduced by Life Technologies as a whole-transcriptome, targeted gene quantification kit to overcome these limitati...

  2. Liver and circulating NK1.1(+)CD3(-) cells are increased in infection with attenuated Salmonella typhimurium and are associated with reduced tumor in murine liver cancer.

    Science.gov (United States)

    Feltis, B A; Miller, J S; Sahar, D A; Kim, A S; Saltzman, D A; Leonard, A S; Wells, C L; Sielaff, T D

    2002-09-01

    An attenuated (DeltacyA, Deltacrp) strain of Salmonella typhimurium (chi4550) containing a gene for human IL-2 (chi4550pIL2) reduces hepatic tumor burden when orally inoculated into mice with liver cancer; however, wild-type S. typhimurium is also associated with cancer regression. Therefore, experiments were designed to clarify the invasiveness and the anti-tumor properties of three strains of S. typhimurium. S. typhimurium chi4550pIL2, chi4550, or wild type (WT) was incubated with mature Caco-2 and HT-29 enterocytes, and S. typhimurium internalization was assessed. For infectivity experiments, mice were orally inoculated with saline or 10(9)S. typhimurium chi4550pIL2, chi4550, or WT; 48 h later mice were sacrificed for analysis of cecal bacteria and S. typhimurium translocation to mesenteric lymph nodes. For experiments involving tumor implantation, four groups were studied: saline control, tumor alone, chi4550pIL2+tumor, and chi4550+tumor. Mice were orally inoculated with saline or S. typhimurium and underwent laparotomy 24 h later with 5 x 10(4) MCA38 murine adenocarcinoma cells injected into the spleen. On day 14, liver tumors were counted and peripheral blood and hepatic lymphocyte populations were analyzed by FACScan. Attenuated S. typhimurium exhibited decreased internalization by cultured enterocytes and decreased infectivity after oral inoculation. Mice treated with chi4550pIL2 or chi4550 had fewer liver tumors and increased populations of hepatic and circulating NK1.1(+)CD3(-) lymphocytes compared to mice treated with saline (P < 0.01). These data suggest that attenuated S. typhimurium may have an application as an anti-tumor agent.

  3. Knowledge of pathologically versus clinically negative lymph nodes is associated with reduced use of radioactive iodine post-thyroidectomy for low-risk papillary thyroid cancer.

    Science.gov (United States)

    Ruel, Ewa; Thomas, Samantha; Dinan, Michaela A; Perkins, Jennifer M; Roman, Sanziana A; Sosa, Julie Ann

    2016-06-01

    Cervical lymph node metastases are common in papillary thyroid cancer (PTC). Clinically negative lymph nodes confer uncertainty about true lymph node status, potentially prompting empiric postoperative radioactive iodine (RAI) administration even in low-risk patients. We examined the association of clinically (cN0) versus pathologically negative (pN0) lymph nodes with utilization of RAI for low-risk PTC. Using the National Cancer Database 1998-2011, adults with PTC who underwent total thyroidectomy for Stage I/II tumors 1-4 cm were evaluated for receipt of RAI based on cN0 versus pN0 status. Cut-point analysis was conducted to determine the number of pN0 nodes associated with the greatest decrease in the odds of receipt of RAI. Survival models and multivariate analyses predicting RAI use were conducted separately for all patients and patients negative surgical margins and multifocal disease (all p negative nodes reported in surgical pathology specimens was 4; ≥5 pathologically negative lymph nodes provided the best cut-point associated with reduced RAI administration (OR 0.91, CI 0.85-0.97). After multivariable adjustment, pN0 patients with ≥5 nodes examined were less likely to receive RAI compared to cN0 patients across all ages (OR 0.89, p negative lymph nodes in patients with PTC appears to influence the decision to administer postoperative RAI if ≥5 negative lymph nodes are removed. It is possible that fewer excised lymph nodes may be viewed by clinicians as incidentally resected and thus may suboptimally represent the true nodal status of the central neck. Further research is warranted to determine if there is an optimal number of lymph nodes that should be resected to standardize pathological diagnosis.

  4. Enhanced G2/M Arrest, Caspase Related Apoptosis and Reduced E-Cadherin Dependent Intercellular Adhesion by Trabectedin in Prostate Cancer Stem Cells

    Science.gov (United States)

    Uslu, Ruchan; Kara, Mikail; Soner, Burak Cem; Oktem, Gulperi

    2015-01-01

    Trabectedin (Yondelis, ET-743) is a marine-derived tetrahydroisoquinoline alkaloid. It is originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and currently produced synthetically. Trabectedin is active against a variety of tumor cell lines growing in culture. The present study focused on the effect of trabectedin in cell proliferation, cell cycle progression, apoptosis and spheroid formation in prostate cancer stem cells (CSCs). Cluster of differentiation (CD) 133+high/CD44+high prostate CSCs were isolated from the DU145 and PC-3 human prostate cancer cell line through flow cytometry. We studied the growth-inhibitory effects of trabectedin and its molecular mechanisms on human prostate CSCs and non-CSCs. DU-145 and PC-3 CSCs were treated with 0.1, 1, 10 and 100 nM trabectedin for 24, 48 and 72 h and the growth inhibition rates were examined using the sphere-forming assay. Annexin-V assay and immunofluorescence analyses were performed for the detection of the cell death. Concentration-dependent effects of trabectedin on the cell cycle were also evaluated. The cells were exposed to the different doses of trabectedin for 24, 48 and 72 h to evaluate the effect of trabectedin on the number and diameter of spheroids. According to the results, trabectedin induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspase-3, caspase-8, caspase-9, p53 and decrease expression of bcl-2 in dose-dependent manner. Cell cycle analyses revealed that trabectedin induces dose-dependent G2/M-phase cell cycle arrest, particularly at high-dose treatments. Three-dimensional culture studies showed that trabectedin reduced the number and diameter of spheroids of DU145 and PC3 CSCs. Furthermore, we have found that trabectedin disrupted cell-cell interactions via E-cadherin in prostasphere of DU-145 and PC-3 CSCs. Our results showed that trabectedin inhibits cellular proliferation and accelerates apoptotic events in

  5. Enhanced G2/M Arrest, Caspase Related Apoptosis and Reduced E-Cadherin Dependent Intercellular Adhesion by Trabectedin in Prostate Cancer Stem Cells.

    Directory of Open Access Journals (Sweden)

    Eda Acikgoz

    Full Text Available Trabectedin (Yondelis, ET-743 is a marine-derived tetrahydroisoquinoline alkaloid. It is originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and currently produced synthetically. Trabectedin is active against a variety of tumor cell lines growing in culture. The present study focused on the effect of trabectedin in cell proliferation, cell cycle progression, apoptosis and spheroid formation in prostate cancer stem cells (CSCs. Cluster of differentiation (CD 133+high/CD44+high prostate CSCs were isolated from the DU145 and PC-3 human prostate cancer cell line through flow cytometry. We studied the growth-inhibitory effects of trabectedin and its molecular mechanisms on human prostate CSCs and non-CSCs. DU-145 and PC-3 CSCs were treated with 0.1, 1, 10 and 100 nM trabectedin for 24, 48 and 72 h and the growth inhibition rates were examined using the sphere-forming assay. Annexin-V assay and immunofluorescence analyses were performed for the detection of the cell death. Concentration-dependent effects of trabectedin on the cell cycle were also evaluated. The cells were exposed to the different doses of trabectedin for 24, 48 and 72 h to evaluate the effect of trabectedin on the number and diameter of spheroids. According to the results, trabectedin induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspase-3, caspase-8, caspase-9, p53 and decrease expression of bcl-2 in dose-dependent manner. Cell cycle analyses revealed that trabectedin induces dose-dependent G2/M-phase cell cycle arrest, particularly at high-dose treatments. Three-dimensional culture studies showed that trabectedin reduced the number and diameter of spheroids of DU145 and PC3 CSCs. Furthermore, we have found that trabectedin disrupted cell-cell interactions via E-cadherin in prostasphere of DU-145 and PC-3 CSCs. Our results showed that trabectedin inhibits cellular proliferation and accelerates

  6. Transcriptomic response to differentiation induction

    Directory of Open Access Journals (Sweden)

    Dimitrov DS

    2006-02-01

    Full Text Available Abstract Background Microarrays used for gene expression studies yield large amounts of data. The processing of such data typically leads to lists of differentially-regulated genes. A common terminal data analysis step is to map pathways of potentially interrelated genes. Methods We applied a transcriptomics analysis tool to elucidate the underlying pathways of leukocyte maturation at the genomic level in an established cellular model of leukemia by examining time-course data in two subclones of U-937 cells. Leukemias such as Acute Promyelocytic Leukemia (APL are characterized by a block in the hematopoietic stem cell maturation program at a point when expansion of clones which should be destined to mature into terminally-differentiated effector cells get locked into endless proliferation with few cells reaching maturation. Treatment with retinoic acid, depending on the precise genomic abnormality, often releases the responsible promyelocytes from this blockade but clinically can yield adverse sequellae in terms of potentially lethal side effects, referred to as retinoic acid syndrome. Results Briefly, the list of genes for temporal patterns of expression was pasted into the ABCC GRID Promoter TFSite Comparison Page website tool and the outputs for each pattern were examined for possible coordinated regulation by shared regelems (regulatory elements. We found it informative to use this novel web tool for identifying, on a genomic scale, genes regulated by dru