Grade, Marian

[["dc.bibliographiccitation.firstpage","1184"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Radiation Oncology*Biology*Physics"],["dc.bibliographiccitation.lastpage","1192"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Scharf, Jens-Gerd"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Ghadimi, Michael B."],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Grade, Marian"],["dc.date.accessioned","2018-11-07T08:36:51Z"],["dc.date.available","2018-11-07T08:36:51Z"],["dc.date.issued","2010"],["dc.description.abstract","Purpose: The standard treatment of patients with locally advanced rectal cancers comprises preoperative 5-fluorouracil based chemoradiotherapy followed by standardized surgery. However, tumor response to multimodal treatment has varied greatly, ranging from complete resistance to complete pathologic regression. The prediction of the response is, therefore, an important clinical need. Methods and Materials: To establish in vitro models for studying the molecular basis of this heterogeneous tumor response, we exposed 12 colorectal cancer cell lines to 3 mu M of 5-fluorouracil and 2 Gy of radiation. The differences in treatment sensitivity were then correlated with the pretherapeutic gene expression profiles of these cell lines. Results: We observed a heterogeneous response, with surviving fractions ranging from 0.28 to 0.81, closely recapitulating clinical reality. Using a linear model analysis, we identified 4,796 features whose expression levels correlated significantly with the sensitivity to chemoradiotherapy (Q < .05), including many genes involved in the mitogen-activated protein kinase signaling pathway or cell cycle genes. These data have suggested a potential relevance of the insulin and Wnt signaling pathways for treatment response, and we identified STAT3, RASSF1, DOK3, and ERBB2 as potential therapeutic targets. The microarray measurements were independently validated for a subset of these genes using real-time polymerase chain reactions. Conclusion: We are the first to report a gene expression signature for the in vitro chemoradiosensitivity of colorectal cancer cells. We anticipate that this analysis will unveil molecular biomarkers predictive of the response of rectal cancers to chemoradiotherapy and enable the identification of genes that could serve as targets to sensitize a priori resistant primary tumors. (C) 2010 Elsevier Inc."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [KFO 179]"],["dc.identifier.doi","10.1016/j.ijrobp.2010.06.023"],["dc.identifier.isi","000283963100030"],["dc.identifier.pmid","20970032"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6106"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18405"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0360-3016"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","A GENE EXPRESSION SIGNATURE FOR CHEMORADIOSENSITIVITY OF COLORECTAL CANCER CELLS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1284"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.lastpage","1295"],["dc.bibliographiccitation.volume","68"],["dc.contributor.author","Camps, Jordi"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Nguyen, Quang Tri"],["dc.contributor.author","Hoermann, Patrick"],["dc.contributor.author","Becker, Sandra"],["dc.contributor.author","Hummon, Amanda B."],["dc.contributor.author","Rodriguez, Virginia"],["dc.contributor.author","Chandrasekharappa, Settara"],["dc.contributor.author","Chen, Yidong"],["dc.contributor.author","Difilippantonio, Michael J."],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Ried, Thomas"],["dc.date.accessioned","2018-11-07T11:17:24Z"],["dc.date.available","2018-11-07T11:17:24Z"],["dc.date.issued","2008"],["dc.description.abstract","Genomic aberrations on chromosome 8 are common in colon cancer, and are associated with lymph node and distant metastases as well as with disease susceptibility. This prompted us to generate a high-resolution map of genomic imbalances of chromosome 8 in 51 primary colon carcinomas using a custom-designed genomic array consisting of a tiling path of BAC clones. This analysis confirmed the dominant role of this chromosome. Unexpectedly, the position of the breakpoints suggested colocalization with structural variants in the human genome. In order to map these sites with increased resolution and to extend the analysis to the entire genome, we analyzed a subset of these tumors (n = 32) by comparative genomic hybridization on a 185K oligonucleotide array platform. Our comprehensive map of the colon cancer genome confirmed recurrent and specific low-level copy number changes of chromosomes 7, 8, 13, 18, and 20, and unveiled additional, novel sites of genomic imbalances including amplification of a histone gene cluster on chromosome 6p21.1-21.33 and deletions on chromosome 4q34-35. The systematic comparison of segments of copy number change with gene expression profiles showed that genomic imbalances directly affect average expression levels. Strikingly, we observed a significant association of chromosomal breakpoints with structural variants in the human genome: 41% of all copy number changes occurred at sites of such copy number variants (P < 2.2e(-16)). Such an association has not been previously described and reveals a yet underappreciated plasticity of the colon cancer genome; it also points to potential mechanisms for the induction of chromosomal breakage in cancer cells."],["dc.description.sponsorship","Intramural NIH HHS [Z99 CA999999]"],["dc.identifier.doi","10.1158/0008-5472.CAN-07-2864"],["dc.identifier.isi","000253802200007"],["dc.identifier.pmid","18316590"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6102"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54798"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","0008-5472"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Chromosomal breakpoints in primary colon cancer cluster at sites of structural variants in the genome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","19432"],["dc.bibliographiccitation.issue","49"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","19437"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Garman, Katherine S."],["dc.contributor.author","Acharya, Chaitanya R."],["dc.contributor.author","Edelman, Elena"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Sud, Shivani"],["dc.contributor.author","Barry, William"],["dc.contributor.author","Diehl, Anna Mae"],["dc.contributor.author","Provenzale, Dawn"],["dc.contributor.author","Ginsburg, Geoffrey S."],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Nevins, Joseph R."],["dc.contributor.author","Mukherjee, Sayan"],["dc.contributor.author","Hsu, David"],["dc.contributor.author","Potti, Anil"],["dc.date.accessioned","2018-11-07T11:08:03Z"],["dc.date.available","2018-11-07T11:08:03Z"],["dc.date.issued","2008"],["dc.description.abstract","Gene expression profiles provide an opportunity to dissect the heterogeneity of solid tumors, including colon cancer, to improve prognosis and predict response to therapies. Bayesian binary regression methods were used to generate a signature of disease recurrence in patients with resected early stage colon cancer validated in an independent cohort. A 50-gene signature was developed that effectively distinguished early stage colon cancer patients with a low or high risk of disease recurrence. RT-PCR analysis of the 50-gene signature validated 9 of the top 10 differentially expressed genes. When applied to two independent validation cohorts of 55 and 73 patients, the 50-gene model accurately predicted recurrence. Standard Kaplan-Meier survival analysis confirmed the prognostic accuracy (P < 0.01, log rank), as did multivariate Cox proportional hazard models. Wetested potential targeted therapeutic options for patients at high risk for disease recurrence and found a clinically important relationship between sensitivity to celecoxib, LY-294002 (PI3kinase inhibitor), retinol, and sulindac in colon cancer cell lines expressing the poor prognostic phenotype (P < 0.01, t test), which performed better than standard chemotherapy (5-FU and oxaliplatin). We present a genomic strategy in early stage colon cancer to identify patients at highest risk of recurrence. An ability to move beyond current staging by refining the estimation of prognosis in early stage colon cancer also has implications for individualized therapy."],["dc.identifier.doi","10.1073/pnas.0806674105"],["dc.identifier.isi","000261706600073"],["dc.identifier.pmid","19050079"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6104"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/52706"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities (Retracted Article. See vol 106, pg 6878, 2009)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1"],["dc.bibliographiccitation.journal","Molecular Cancer"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Hummon, Amanda B."],["dc.contributor.author","Pitt, Jason J."],["dc.contributor.author","Camps, Jordi"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Skube, Susan B."],["dc.contributor.author","Huppi, Konrad"],["dc.contributor.author","Jones, Tamara L."],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Grade, Marian"],["dc.contributor.author","Difilippantonio, Michael J."],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Caplen, Natasha J."],["dc.date.accessioned","2018-11-07T09:14:27Z"],["dc.date.available","2018-11-07T09:14:27Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Colorectal carcinomas (CRC) carry massive genetic and transcriptional alterations that influence multiple cellular pathways. The study of proteins whose loss-of-function (LOF) alters the growth of CRC cells can be used to further understand the cellular processes cancer cells depend upon for survival. Results: A small-scale RNAi screen of similar to 400 genes conducted in SW480 CRC cells identified several candidate genes as required for the viability of CRC cells, most prominently CASP8AP2/FLASH. To understand the function of this gene in maintaining the viability of CRC cells in an unbiased manner, we generated gene specific expression profiles following RNAi. Silencing of CASP8AP2/FLASH resulted in altered expression of over 2500 genes enriched for genes associated with cellular growth and proliferation. Loss of CASP8AP2/FLASH function was significantly associated with altered transcription of the genes encoding the replication-dependent histone proteins as a result of the expression of the non-canonical polyA variants of these transcripts. Silencing of CASP8AP2/FLASH also mediated enrichment of changes in the expression of targets of the NF kappa B and MYC transcription factors. These findings were confirmed by whole transcriptome analysis of CASP8AP2/FLASH silenced cells at multiple time points. Finally, we identified and validated that CASP8AP2/FLASH LOF increases the expression of neurofilament heavy polypeptide (NEFH), a protein recently linked to regulation of the AKT1/beta-catenin pathway. Conclusions: We have used unbiased RNAi based approaches to identify and characterize the function of CASP8AP2/FLASH, a protein not previously reported as required for cell survival. This study further defines the role CASP8AP2/FLASH plays in the regulating expression of the replication-dependent histones and shows that its LOF results in broad and reproducible effects on the transcriptome of colorectal cancer cells including the induction of expression of the recently described tumor suppressor gene NEFH."],["dc.description.sponsorship","NIH, National Cancer Institute, Center for Cancer Research; NCI"],["dc.identifier.doi","10.1186/1476-4598-11-1"],["dc.identifier.isi","000301603300001"],["dc.identifier.pmid","22216762"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7195"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27412"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1476-4598"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Systems-wide RNAi analysis of CASP8AP2/FLASH shows transcriptional deregulation of the replication-dependent histone genes and extensive effects on the transcriptome of colorectal cancer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]