Valeur pronostique du dosage intratumoral des glutathion S-transférases dans les carcinomes épidermoïdes de l'oesophage traités par chimioradiothérapie

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Reply to Caccialanza et al.

International audienceA double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX. Boisselier P, Kaminsky MC, Thézenas S, Gallocher O, Lavau-Denes S, Garcia-Ramirez M, Alfonsi M, Cupissol D, de Forges H, Janiszewski C, Geoffrois L, Sire C, Senesse P; Head and Neck Oncology and Radiotherapy Group (GORTEC). Am J Clin Nutr. 2020 Dec 10;112(6):1523-1531. doi: 10.1093/ajcn/nqaa227. PMID: 32936874 Clinical Trial. Immunonutrition in head and neck cancer patients undergoing chemoradiotherapy: an alternative approach for overcoming potential bias. Caccialanza R, Cereda E, Orlandi E, Filippi AR, Comoli P, Alberti A, Imarisio I, Pedrazzoli P, Bossi P. Am J Clin Nutr. 2021 Apr 6;113(4):1053-1054. doi: 10.1093/ajcn/nqaa421. PMID: 33822867 No abstract available

ERK2 but not ERK1 plays a key role in hepatocyte replication: an RNAi-mediated ERK2 knockdown approach in wild-type and ERK1 null hepatocytes.

The mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 have been implicated in various physiological events, and specific targeting of these MAPKs could affect cell proliferation in many cell types. First, to evaluate the potential specific roles of these two MAPKs, we analyzed the mitogenic response in regenerating liver after partial hepatectomy (PH) and in primary culture of hepatocytes isolated from ERK1-deficient mice. We show that ERK1 knockout and wild-type (wt) cells replicate with the same kinetics after PH in liver, in vivo, and in primary cultures of hepatocytes, in vitro. Indeed, Cyclin D1 and Cdk1 appear to be expressed concomitantly in knockout and wt cells, highlighting that hepatocytes progress in the cell cycle independently of the presence of ERK1. Second, we specifically abolished ERK2 expression by RNA interference in mouse and rat hepatocytes. We investigated whether small interfering RNA (siRNA) targeting ERK2 could specifically inhibit its expression and interfere with the process of replication. In ERK1-deficient hepatocytes, silencing ERK2 expression by RNA interference and ERK2 activation by U0126 clearly demonstrate that DNA replication is regulated by an ERK2-dependent mechanism. Furthermore, in rat wt hepatocytes, whereas ERK2 targeting inhibits late G(1) and S phase progression, ERK1 silencing is devoid of any effect on cell proliferation, indicating that ERK1 cannot rescue ERK2 deficiency. CONCLUSION: Our results emphasize the importance of the MAPK cascade in hepatocyte replication and allow us to conclude that ERK2 is the key form involved in this regulation, in vivo and in vitro

Tracking, gating, free-breathing, which technique to use for lung stereotactic treatments? A dosimetric comparison

BackgroundThe management of breath-induced tumor motion is a major challenge for lung stereotactic body radiation therapy (SBRT). Three techniques are currently available for these treatments: tracking (T), gating (G) and free-breathing (FB).AimTo evaluate the dosimetric differences between these three treatment techniques for lung SBRT.Materials and methodsPretreatment 4DCT data were acquired for 10 patients and sorted into 10 phases of a breathing cycle, such as 0% and 50% phases defined respectively as the inhalation and exhalation maximum. GTVph, PTVph (=GTVph+3mm) and the ipsilateral lung were contoured on each phase.For the tracking technique, 9 fixed fields were adjusted to each PTVph for the 10 phases. The gating technique was studied with 3 exhalation phases (40%, 50% and 60%). For the free-breathing technique, ITVFB was created from a sum of all GTVph and a 3mm margin was added to define a PTVFB. Fields were adjusted to PTVFB and dose distributions were calculated on the average intensity projection (AIP) CT. Then, the beam arrangement with the same monitor units was planned on each CT phase.The 3 modalities were evaluated using DVHs of each GTVph, the homogeneity index and the volume of the ipsilateral lung receiving 20Gy (V20Gy).ResultsThe FB system improved the target coverage by increasing Dmean (75.87(T)–76.08(G)–77.49(FB)Gy). Target coverage was slightly more homogeneous, too (HI: 0.17(T and G)–0.15(FB)). But the lung was better protected with the tracking system (V20Gy: 3.82(T)–4.96(G)–6.34(FB)%).ConclusionsEvery technique provides plans with a good target coverage and lung protection. While irradiation with free-breathing increases doses to GTV, irradiation with the tracking technique spares better the lung but can dramatically increase the treatment complexity

Tracking, gating, free-breathing, which technique to use for lung stereotactic treatments? A dosimetric comparison

International audienceBackground:The management of breath-induced tumor motion is a major challenge for lung stereotactic body radiation therapy (SBRT). Three techniques are currently available for these treatments: tracking (T), gating (G) and free-breathing (FB).Aim:To evaluate the dosimetric differences between these three treatment techniques for lung SBRT.Materials and methods:Pretreatment 4DCT data were acquired for 10 patients and sorted into 10 phases of a breathing cycle, such as 0% and 50% phases defined respectively as the inhalation and exhalation maximum. GTVph, PTVph (=GTVph + 3 mm) and the ipsilateral lung were contoured on each phase.For the tracking technique, 9 fixed fields were adjusted to each PTVph for the 10 phases. The gating technique was studied with 3 exhalation phases (40%, 50% and 60%). For the free-breathing technique, ITVFB was created from a sum of all GTVph and a 3 mm margin was added to define a PTVFB. Fields were adjusted to PTVFB and dose distributions were calculated on the average intensity projection (AIP) CT. Then, the beam arrangement with the same monitor units was planned on each CT phase.The 3 modalities were evaluated using DVHs of each GTVph, the homogeneity index and the volume of the ipsilateral lung receiving 20 Gy (V 20Gy).Results:The FB system improved the target coverage by increasing D mean (75.87(T)-76.08(G)-77.49(FB)Gy). Target coverage was slightly more homogeneous, too (HI: 0.17(T and G)-0.15(FB)). But the lung was better protected with the tracking system (V 20Gy: 3.82(T)-4.96(G)-6.34(FB)%).Conclusions:Every technique provides plans with a good target coverage and lung protection. While irradiation with free-breathing increases doses to GTV, irradiation with the tracking technique spares better the lung but can dramatically increase the treatment complexity

Etude de phase II sur l’efficacité et la tolérance d’une augmentation de dose de radiothérapie des lésions hypoxiques définies par TEP-scanographie au fluoromisonidazole chez les patients suivis pour un cancer bronchique non à petites cellules

International audienc

NOTCH2 is neither rearranged nor mutated in t(1;19) positive oligodendrogliomas.

The combined deletion of 1p and 19q chromosomal arms is frequent in oligodendrogliomas (OD) and has recently been shown to be mediated by an unbalanced t(1;19) translocation. Recent studies of 1p/19q co-deleted OD suggest that the NOTCH2 gene is implicated in oligodendrocyte differentiation and may be involved in this rearrangement. The objective of the present study was to analyze the NOTCH2 locus either as a chromosomal translocation locus that may be altered by the 1p/19q recurrent rearrangement or as a gene that may be inactivated by a two hit process. We performed an array-CGH analysis of 15 ODs presenting 1p/19q co-deletion using a high-density oligonucleotide microarray spanning 1p and 19q pericentromeric regions with 377 bp average probe spacing. We showed that the 1p deletion extends to the centromere of chromosome 1 and includes the entire NOTCH2 gene. No internal rearrangement of this gene was observed. This strongly suggests that the t(1;19) translocation does not lead to an abnormal NOTCH2 structure. The analysis of the entire NOTCH2 coding sequence was performed in four cases and did not reveal any mutation therefore indicating that NOTCH2 does not harbor genetic characteristics of a tumor suppressor gene. Finally, the detailed analysis of chromosome 19 pericentromeric region led to the identification of two breakpoint clusters at 19p12 and 19q11-12. Interestingly, these two regions share a large stretch of homology. Together with previous observations of similarities between chromosome 1 and 19 alphoid sequences, this suggests that the t(1;19) translocation arises from complex intra and interchromosomal rearrangements.This is the first comprehensive deletion mapping by high density oligo-array of the 1p/19q co-deletion in oligodendroglioma tumors using a methodological approach superior to others previously applied. As such this paper provides clear evidence that the NOTCH2 gene is not physically rearranged by t(1;19) translocation of oligodendroglioma tumors