Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen

Amundson, Sally A.; Khánh, Trần Vân; Vinikoor, Lisa C.; Lee, R. Anthony; Koch-Paiz, Christine A.; Ahn, Juhyeon; Reimers, Mark; Chen, Yidong; Scudiero, Dominic A.; Weinstein, John N.; Trent, Jeffrey M.; Bittner, Michael; Meltzer, Paul S.; Fornace, Albert J.

doi:10.1158/0008-5472.can-07-2120

Cited by 229 publications

(220 citation statements)

References 38 publications

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“…Our findings here complement a recent gene expression study in directly irradiated and bystander cells that revealed NF-B as the dominant transcription factor in mediating bystander responses (91,92). TNF is one of the key cytokines that activates the NF-B (93).…”

Section: Tnfr2/p75 Regulate Ir-induced Nontargeted Effectssupporting

confidence: 87%

TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Nontargeted Effects in Bone Marrow-derived Endothelial Progenitor Cells

Sasi¹,

Song²,

Park³

et al. 2014

Journal of Biological Chemistry

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Background: Ionizing radiation can induce DNA damage in nonirradiated (N-IR) cells via nontargeted effects (NTE). Results: TNF-␣ and IL-1␣ mediate NTE in N-IR bone marrow-derived EPCs, and neutralizing TNF-␣ diminishes NTE in WT and p55 knock-out BM-EPCs. Conclusion: TNF-TNFR2/p75 signaling alters accumulation of inflammatory cytokines that attenuate NTE in N-IR EPCs. Significance: TNFR2/p75 may represent a gene target for mitigation of delayed RBR in BM-EPCs.

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Section: Tnfr2/p75 Regulate Ir-induced Nontargeted Effectssupporting

confidence: 87%

TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Nontargeted Effects in Bone Marrow-derived Endothelial Progenitor Cells

Sasi¹,

Song²,

Park³

et al. 2014

Journal of Biological Chemistry

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“…KEGG pathways significantly over-represented relative to chance in the set of radiation-repressed genes included "ribosome" (P = 5.45 × 10 −22 ), "cell cycle" (P = 5.24 × 10 −4 ) and "spliceosome" (P = 3.78 × 10 −19 ). The enrichment of genes involved in apoptosis in the radiation-induced gene set, and enrichment of genes involved in mitosis in the radiation-repressed gene set, is consistent with prior studies examining radiation-responsive genes in humans (26)(27)(28)(29) indicating conservation of the radiation responsiveness of these gene ontology categories/ pathways in our mouse model. As for the radiation-induced genes, clusters of radiationrepressed genes showing highly correlated expression were observed (Fig.…”

Section: Identification Of Radiation-responsive Genessupporting

confidence: 88%

“…Many genes identified as radiation induced in our analysis were previously known to be radiation responsive in humans including CREM, BNIP3, FAS, TNFRSF11B, IFITM1, LGALS3PB, COX7B and SESN1 (26)(27)(28)(29), indicating the conservation of the radiation responsiveness of many genes in this p53-deficient mouse model. Using the program DAVID [Database for Annotation, Visualization and Integrated Discovery (30,31); http:// david.abcc.ncifcrf.gov], the gene ontology categories that were significantly overrepresented relative to chance in the set of all radiation-induced genes included: "protein catabolic process" (P = 3.40 × 10 −9 ); "apoptosis" (P = 3.45 × 10 −5 ); "cell death" (P = 1.17 × 10 −4 ) and "macromolecule catabolic process" (P = 8.24 × 10 −8 ).…”

Section: Identification Of Radiation-responsive Genessupporting

confidence: 52%

Radiation-induced Gene Signature Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

Chao

Balletta

et al. 2012

International Journal of Radiation Oncology*Biology*Physics

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The identification of biomarkers predictive of neoadjuvant chemotherapy response in breast cancer patients would be an important advancement in personalized cancer therapy. In this study, we hypothesized that due to similarities between radiation-and chemotherapy-induced cellular response mechanisms, radiation-responsive genes may be useful in predicting response to neoadjuvant chemotherapy. Murine p53 null breast cancer cell lines representative of the luminal, basal-like and claudin-low human breast cancer subtypes were irradiated to identify radiationresponsive genes across subtypes. These murine tumor radiation-induced genes were then converted to their human orthologs, and subsequently tested as a predictor of pathologic complete response (pCR), which was validated on two independent published neoadjuvant chemotherapy datasets of genomic data with chemotherapy response. A radiation-induced gene signature consisting of 30 genes was identified on a training set of 337 human primary breast cancer tumor samples that was prognostic for survival. Mean expression of this signature was calculated for individual samples on two independent published datasets and was found to be significantly predictive of pCR. Multivariate logistic regression analysis in both independent datasets showed 1 Address for correspondence: Leo W. Jenkins Cancer Center, The Brody School of Medicine at East Carolina University, 600 Moye Boulevard, Greenville, NC 27834; oh.daniel.s@gmail.com. Supplementary Fig. S1. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster A shown Fig. 3 (upper left) significantly enriched for genes involved in wound and inflammatory response as determined by DAVID. Supplementary Fig. S2. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster B from Fig. 3 (upper left) significantly enriched for genes involved in M phase, mitotic cell cycle and ribosome as determined by DAVID. Supplementary Fig. S3. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster C from Fig. 3 (upper left) significantly enriched for genes involved in muscle contraction, muscle cell development, and myofibril assembly as determined by DAVID. Supplementary Fig. S4. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster D from Fig. 3 (upper left) significantly enriched for genes involved in positive regulation of mesenchymal cell proliferation, blood vessel development and cell motion as determined by DAVID. Supplementary Fig. S5. http://dx.doi.org/10.1667/RR13485.1.S1; Gene cluster E from Fig. 3 (upper left) significantly enriched for genes involved in zinc ion and DNA binding as determined by DAVID. SUPPLEMENTARY INFORMATION HHS Public Access

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“…The results of the present study emphasize that even for radioresistant tumors, clinical responses of grid therapy may vary with the SF2 value. Some authors 25 , 30 have reported that tumors with different histology may have different SF2 values. Also, they have noted that, for a given tumor with a specific histology, there may be different radiosensitivity characteristics at different anatomical sites.…”

Section: Discussionmentioning

confidence: 99%

Is grid therapy useful for all tumors and every grid block design?

Gholami

Nedaie

Longo

et al. 2016

J Applied Clin Med Phys

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Grid therapy is a treatment technique that has been introduced for patients with advanced bulky tumors. The purpose of this study is to investigate the effect of the radiation sensitivity of the tumors and the design of the grid blocks on the clinical response of grid therapy. The Monte Carlo simulation technique is used to determine the dose distribution through a grid block that was used for a Varian 2100C linear accelerator. From the simulated dose profiles, the therapeutic ratio (TR) and the equivalent uniform dose (EUD) for different types of tumors with respect to their radiation sensitivities were calculated. These calculations were performed using the linear quadratic (LQ) and the Hug‐Kellerer (H‐K) models. The results of these calculations have been validated by comparison with the clinical responses of 232 patients from different publications, who were treated with grid therapy. These published results for different tumor types were used to examine the correlation between tumor radiosensitivity and the clinical response of grid therapy. Moreover, the influence of grid design on their clinical responses was investigated by using Monte Carlo simulations of grid blocks with different hole diameters and different center‐to‐center spacing. The results of the theoretical models and clinical data indicated higher clinical responses for the grid therapy on the patients with more radioresistant tumors. The differences between TR values for radioresistant cells and radiosensitive cells at 20 Gy and 10 Gy doses were up to 50% and 30%, respectively. Interestingly, the differences between the TR values with LQ model and H‐K model were less than 4%. Moreover, the results from the Monte Carlo studies showed that grid blocks with a hole diameters of 1.0 cm and 1.25 cm may lead to about 19% higher TR relative to the grids with hole diameters smaller than 1.0 cm or larger than 1.25 cm (with 95% confidence interval). In summary, the results of this study indicate that grid therapy is more effective for tumors with radioresistant characteristics than radiosensitive tumors.PACS number(s): 87.55.‐x

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Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen

Abstract: The 60 cell lines of the National

Cited by 229 publications

References 38 publications

TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Nontargeted Effects in Bone Marrow-derived Endothelial Progenitor Cells

TNF-TNFR2/p75 Signaling Inhibits Early and Increases Delayed Nontargeted Effects in Bone Marrow-derived Endothelial Progenitor Cells

Radiation-induced Gene Signature Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

Is grid therapy useful for all tumors and every grid block design?

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