PURPOSE: Rectal cancer is often clinically resistant to radiotherapy (RT) and identifying molecular markers to define the biologic basis for this phenomenon would be valuable. The nuclear factor κ-light chain-enhancer of activated B cells (NF-κB) is a potential anti-apoptotic transcription factor that has been associated with resistance to RT in model systems. The present study was designed to evaluate NF-κB activation in patients with rectal cancer undergoing chemoradiotherapy to determine whether NF-κB activity correlates with the outcome in rectal cancer patients. METHODS AND MATERIALS: A total of 22 patients underwent biopsy at multiple points in a prospective study and the data from another 50 were analyzed retrospectively. The pretreatment tumor tissue was analyzed for multiple NF-κB subunits by immunohistochemistry. Serial tumor biopsy cores were analyzed for NF-κB-regulated gene expression using reverse transcriptase polymerase chain reaction and for NF-κB subunit nuclear localization using immunohistochemistry. RESULTS: Several NF-κB target genes (Bcl-2, cellular inhibitor of apoptosis protein [cIAP]2, interleukin-8, and tumor necrosis factor receptor-associated-1) were significantly upregulated by a single fraction of RT at 24 h, demonstrating for the first time that NF-κB is activated by RT in human rectal tumors. The baseline NF-κB p50 nuclear expression did not correlate with the pathologic response to RT. However, an increasing baseline p50 level was prognostic for overall survival (hazard ratio, 2.15; p = .040). CONCLUSION: NF-κB nuclear expression at baseline in rectal cancer was prognostic for overall survival but not predictive of the response to RT. Larger patient numbers are needed to assess the effect of NF-κB target gene upregulation on the response to RT. Our results suggest that NF-κB might play an important role in tumor metastasis but not to the resistance to chemoradiotherapy.
PURPOSE:Rectal cancer is often clinically resistant to radiotherapy (RT) and identifying molecular markers to define the biologic basis for this phenomenon would be valuable. The nuclear factor κ-light chain-enhancer of activated B cells (NF-κB) is a potential anti-apoptotic transcription factor that has been associated with resistance to RT in model systems. The present study was designed to evaluate NF-κB activation in patients with rectal cancer undergoing chemoradiotherapy to determine whether NF-κB activity correlates with the outcome in rectal cancerpatients. METHODS AND MATERIALS: A total of 22 patients underwent biopsy at multiple points in a prospective study and the data from another 50 were analyzed retrospectively. The pretreatment tumor tissue was analyzed for multiple NF-κB subunits by immunohistochemistry. Serial tumor biopsy cores were analyzed for NF-κB-regulated gene expression using reverse transcriptase polymerase chain reaction and for NF-κB subunit nuclear localization using immunohistochemistry. RESULTS: Several NF-κB target genes (Bcl-2, cellular inhibitor of apoptosis protein [cIAP]2, interleukin-8, and tumor necrosis factor receptor-associated-1) were significantly upregulated by a single fraction of RT at 24 h, demonstrating for the first time that NF-κB is activated by RT in humanrectal tumors. The baseline NF-κB p50 nuclear expression did not correlate with the pathologic response to RT. However, an increasing baseline p50 level was prognostic for overall survival (hazard ratio, 2.15; p = .040). CONCLUSION: NF-κB nuclear expression at baseline in rectal cancer was prognostic for overall survival but not predictive of the response to RT. Larger patient numbers are needed to assess the effect of NF-κB target gene upregulation on the response to RT. Our results suggest that NF-κB might play an important role in tumor metastasis but not to the resistance to chemoradiotherapy.
Authors: Sally A Amundson; Richard Anthony Lee; Christine A Koch-Paiz; Michael L Bittner; Paul Meltzer; Jeffrey M Trent; Albert J Fornace Journal: Mol Cancer Res Date: 2003-04 Impact factor: 5.852
Authors: Rolf Sauer; Heinz Becker; Werner Hohenberger; Claus Rödel; Christian Wittekind; Rainer Fietkau; Peter Martus; Jörg Tschmelitsch; Eva Hager; Clemens F Hess; Johann-H Karstens; Torsten Liersch; Heinz Schmidberger; Rudolf Raab Journal: N Engl J Med Date: 2004-10-21 Impact factor: 91.245
Authors: C Didelot; M Barberi-Heyob; A Bianchi; P Becuwe; J F Mirjolet; M Dauça; J L Merlin Journal: Int J Radiat Oncol Biol Phys Date: 2001-12-01 Impact factor: 7.038
Authors: Christopher H Crane; John M Skibber; Elisa H Birnbaum; Barry W Feig; Anurag K Singh; Marc E Delclos; Edward H Lin; James W Fleshman; Howard D Thames; Ira J Kodner; Mary Ann Lockett; Joel Picus; Thinh Phan; Anshu Chandra; Nora A Janjan; Thomas E Read; Robert J Myerson Journal: Int J Radiat Oncol Biol Phys Date: 2003-09-01 Impact factor: 7.038
Authors: Soham D Puvvada; William K Funkhouser; Kevin Greene; Allison Deal; Haitao Chu; Albert S Baldwin; Joel E Tepper; Bert H O'Neil Journal: Oncology Date: 2010-04-23 Impact factor: 2.935
Authors: Antja-Voy Hartley; Benlian Wang; Guanglong Jiang; Han Wei; Mengyao Sun; Lakshmi Prabhu; Matthew Martin; Ahmad Safa; Steven Sun; Yunlong Liu; Tao Lu Journal: Int J Mol Sci Date: 2020-05-23 Impact factor: 5.923
Authors: Juan J Ortiz de Urbina; Beatriz San-Miguel; Alfonso Vidal-Casariego; Irene Crespo; Diana I Sánchez; José L Mauriz; Jesús M Culebras; Javier González-Gallego; María J Tuñón Journal: Int J Med Sci Date: 2017-09-04 Impact factor: 3.738