ARCON: accelerated radiotherapy with carbogen and nicotinamide in head and neck squamous cell carcinomas. The experience of the Co-operative Group of Radiotherapy of the European Organization for Research and Treatment of Cancer (EORTC)

Bernier, Jacques; Denekamp, Juliana; Rojas, Á.; Minatel, Emilio; Horiot, J.C.; Hamers, Han; Antognoni, Paolo; Dahl, Øyvind; Richaud, Pierre; Glabbeke, M. van; Piérart, M.

doi:10.1016/s0167-8140(00)00165-1

Cited by 54 publications

(26 citation statements)

References 36 publications

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“…However, it has largely been used in the clinic at pharmacological doses over many years with a low incidence of side effects and toxicity for diverse conditions including dermatological, metabolic and psychiatric disorders (19-22). In cancer, NAM has been used in clinical studies in combination with accelerated radiotherapy with carbogen and nicotinamide (ARCON) for radiosensitation (12,(16)(17)(18). In the present study, we demonstrate that NAM effectively inhibits PARP activity in vitro, results that are consistent with those of previous reports (13).…”

Section: Discussionsupporting

confidence: 92%

“…Preclinical studies have shown that NAM may exert antitumor effects and reverse chemotherapy resistance in some models (14). In addition, this drug is currently used as a component of accelerated radiotherapy with carbogen and nicotinamide (ARCON), a therapeutic strategy used in non-small cell lung cancer, head and neck and bladder cancer (15)(16)(17)(18). In the present study, the results showed that NAM increased the cytotoxic effects of cisplatin and radiation on breast cancer cells.…”

Section: Introductionmentioning

confidence: 52%

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Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin

et al. 2014

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Abstract. Poly(ADP-ribose) polymerase (PARP) inhibitors enhance the effect of DNA alkylating agents on BRCA1-and BRCA2-deficient cell lines. The aim of this study was to analyze the effect of the PARP inhibitor nicotinamide (NAM) on breast cancer cells with different BRCA1 expression or function, such as BRCA1-deficient MDA-MB-436 cells, low expression BRCA1 MCF-7 cells, and the BRCA1 wild-type MDA-MB-231 cells, to demonstrate its effects as a chemoor radiosensitizing agent. PARP activity was analyzed in MDA-MB-436, MCF-7 and MDA-MB-231 breast cancer cells subjected or not to NAM. Inhibition of PARP by NAM in the presence of DNA damage was examined by Alexa Fluor 488 immunofluorescence. Crystal violet assays were used to test growth inhibition and the chemo-and radiosensitization effects of NAM were investigated using clonogenic assays. Significant differences among data sets were determined using two-tailed ANOVA and Bonferroni tests. We demonstrated that NAM reduces PARP activity in vitro, and in cells subjected or not to DNA damage, it also reduces the viability of breast cancer cell lines and synergyzes the cytotoxicity of cisplatin in MDA-MB-436 and MCF-7 cells. Downregulation of PARP1 with siRNA led to modest growth inhibition, which was further increased by cisplatin. Nicotinamide also induced radiosensitization in MDA-MB-436 and MDA-MB-231 cells. In conclusion, NAM may be used as a chemo-or radiosensitizing agent regardless of the BRCA1 status in breast cancer.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 52%

Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin

et al. 2014

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“…If the earliest stages of metastatic developmental in human patients follow a similar pattern, the majority of these microscopic tumors will be hypoxic and thus resistant to ionizing radiation and several chemotherapeutic agents. Clinical and preclinical studies on radiotherapy given in combination with hypoxia modulating agents have shown some promising results in macroscopic tumors (35)(36)(37)(38)(39). The present study indicates that carbogen breathing significantly decreased hypoxia in avascular microscopic tumors.…”

Section: Discussionsupporting

confidence: 58%

Visualization of Hypoxia in Microscopic Tumors by Immunofluorescent Microscopy

et al. 2007

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Tumor hypoxia is commonly observed in primary solid malignancies but the hypoxic status of subclinical micrometastatic disease is largely unknown. The distribution of hypoxia in microscopic tumors was studied in animal models of disseminated peritoneal disease and intradermal (i.d.) growing tumors. Tumors derived from human colorectal adenocarcinoma cell lines HT29 and HCT-8 ranged in size from a few hundred microns to several millimeters in diameter. Hypoxia was detected by immunofluorescent visualization of pimonidazole and the hypoxia-regulated protein carbonic anhydrase 9. Tumor blood perfusion, cellular proliferation, and vascularity were visualized using Hoechst 33342, bromodeoxyuridine, and CD31 staining, respectively. In general, tumors of <1 mm diameter were intensely hypoxic, poorly perfused, and possessed little to no vasculature. Larger tumors (f1-4 mm diameter) were well perfused with widespread vasculature and were not significantly hypoxic. Patterns of hypoxia in disseminated peritoneal tumors and i.d. tumors were similar. Levels of hypoxia in microscopic peritoneal tumors were reduced by carbogen breathing. Peritoneal and i.d. tumor models are suitable for studying hypoxia in microscopic tumors. If the patterns of tumor hypoxia in human patients are similar to those observed in these animal experiments, then the efficacy of systemic treatments of micrometastatic disease may be compromised by hypoxic resistance. [Cancer Res 2007;67(16):7646-53]

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“…Nicotinamide has consistently been assayed in clinical trials in combination with carbogen and was found to potentiate the effect of radiotherapy in head and neck carcinoma (64), although its applicability was limited by severe gastrointestinal toxicity (65). Ever since, evidence for a vasoactive effect of nicotinamide has accumulated (63,66,67), and it has been proposed that this effect accounts for the increased cure of xenografted tumors by radiation (66).…”

Section: Arrest Of Replication Parallels Radiosensitization By Animentioning

confidence: 99%

Radiosensitization by the poly(ADP-ribose) polymerase inhibitor 4-amino-1,8-naphthalimide is specific of the S phase of the cell cycle and involves arrest of DNA synthesis

Noël

Godon

Fernet

et al. 2006

Molecular Cancer Therapeutics

114

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ARCON: accelerated radiotherapy with carbogen and nicotinamide in head and neck squamous cell carcinomas. The experience of the Co-operative Group of Radiotherapy of the European Organization for Research and Treatment of Cancer (EORTC)

Cited by 54 publications

References 36 publications

Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin

Nicotinamide sensitizes human breast cancer cells to the cytotoxic effects of radiation and cisplatin

Visualization of Hypoxia in Microscopic Tumors by Immunofluorescent Microscopy

Radiosensitization by the poly(ADP-ribose) polymerase inhibitor 4-amino-1,8-naphthalimide is specific of the S phase of the cell cycle and involves arrest of DNA synthesis

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