Radiation induces different changes in expression profiles of normal rectal tissue compared with rectal carcinoma

Nagtegaal, Irıs D.; Gaspar, Cláudia; Peltenburg, L. T. C.; Marijnen, Corrie A.M.; Velde, Cornelis J.H. van de; Fodde, Riccardo; Krieken, J.H.J.M. van

doi:10.1007/s00428-004-1160-8

Cited by 16 publications

(11 citation statements)

References 34 publications

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“…Understanding the reasons for partial response to preoperative RCT is of utmost importance and numerous studies have already addressed this issue [2,8,9,14,19,20,23,30,44]. It was shown that radiotherapy may induce changes at the genetic level [21,22], particularly in those genes regulating proliferation, apoptosis, and tissue repair. This might explain the morphological modifications observed in tissues after RCT.…”

Section: Discussionmentioning

confidence: 98%

Oncocytic modifications in rectal adenocarcinomas after radio and chemotherapy

et al. 2005

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The purpose of the study is to highlight oncocytic modifications in rectal adenocarcinomas and evaluate a possible correlation with preoperative radiochemotherapy (RCT). Twenty-eight cases of advanced rectal carcinoma, treated preoperatively by 5-fluorouracil (200-225 mg/m(2)) and 44-46 Gy in 22-23 fractions, were studied. All patients underwent biopsy before RCT. Surgery was performed within 6 weeks after RCT. In all cases oncocytic modifications were searched for on hematoxylin and eosin (H&E) and at immunohistochemistry using an antimitochondrial antibody. In addition, in two cases, both pre- and post-RCT tissues were examined at electron microscopy. All tumors were adenocarcinomas. In pre-RCT biopsies, oncocytic changes were difficult to find on H&E, while the antimitochondrial antibody strongly stained numerous neoplastic cells (mean 48.4%). In post-RCT surgical specimens, oncocytic changes were detected in 24 out of 28 cases on H&E and the antimitochondrial antibody stained most of the residual neoplastic cells (mean 76.7%). Ultrastructural examination revealed large and bizarre mitochondria inside tumor cells both in pre- and post-RCT tissues. In conclusion, the present data suggest that rectal adenocarcinomas are "mitochondrion-rich" tumors. After preoperative RCT, residual neoplastic cells acquire a definite oncocytic phenotype.

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Section: Discussionmentioning

confidence: 98%

Oncocytic modifications in rectal adenocarcinomas after radio and chemotherapy

et al. 2005

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“…Effect of epigenetically controlled genes on radiosensitivity Gene expression of SERPINB5 and S100A6 is reportedly controlled by methylation (Futscher et al, 2002;Rehman et al, 2004); however, the effect of SERPINB5 and S100A6 expression on radiosensitivity has not been studied in depth, although expression of these genes is induced by ionizing radiation (Nagtegaal et al, 2005;Orre et al, 2007). Using siRNAs, we lowered the levels of SERPINB5 and S100A6 in H460 cells and then examined the cell survival rate after exposure to g-irradiation at 2, 5 or 8 Gy (Figure 3).…”

Section: Validation Of Cpg Methylation and Mrna Expressionmentioning

confidence: 99%

Global analysis of CpG methylation reveals epigenetic control of the radiosensitivity in lung cancer cell lines

et al. 2010

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Epigenetic regulation by CpG methylation has an important role in tumorigenesis as well as in the response to cancer therapy. To analyze the mechanism of epigenetic control of radiosensitivity, the CpG methylation profiles of radiosensitive H460 and radioresistant H1299 human non-small cell lung cancer (NSCLC) cell lines were analyzed using microarray profiling. These analyses revealed 1091 differentially methylated genes (DMG) (absolute difference of mean b-values, |Db % |40.5), including genes involved in cell adhesion, cell communication, signal transduction and transcriptional regulation. Among the 747 genes hypermethylated in radioresistant H1299 cells, CpG methylation of SERPINB5 and S100A6 in radioresistant H1299 cells was confirmed by methylationspecific PCR. Reverse transcriptase-PCR showed higher expression of these two genes in radiosensitive H460 cells compared with radioresistant H1299 cells. Downregulation of SERPINB5 or S100A6 by small interfering RNA in H460 cells increased the resistance of these cells to ionizing radiation. In contrast, promoter CpG sites of 344 genes, including CAT and BNC1, were hypomethylated in radioresistant H1299 cells. Suppression of CAT or BNC1 mRNA expression in H1299 cells also reduced the resistance of these cells to ionizing radiation. Thus, we identified DMGs by genome-wide CpG methylation profiling in two NSCLC cell lines with different responses to ionizing radiation, and our data indicated that these differences may be critical for epigenetic regulation of radiosensitivity in lung cancer cells.

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“…The pelvic position of the rectum leads to surgical limits; and thereby, an increased risk of local recurrence and poorer overall prognosis. Preoperative radiotherapy is widely used as a complement to surgery in rectal cancer treatment (Wolpin et al 2007) and it decreases the local recurrence by more than 60%, thereby increasing the overall survival (Nagtegaal et al 2005). There are yet many patients that do not respond to radiotherapy treatment.…”

Section: Introductionmentioning

confidence: 99%