[Combination radiotherapy-immunotherapy in genitourinary cancer]. / Combinaison radiothérapie-immunothérapie en cancérologie génito-urinaire.

Immunotherapy occupies a growing place in urologic oncology, mainly for kidney and bladder cancers. On the basis of encouraging preclinical work, the combination of immunotherapy with radiotherapy aims to increase the tumor response, including in metastatic tumors, which raises many hopes, which this article reviews.

The P2 promoter of the IGF1 gene is a major epigenetic locus for GH responsiveness.

Short children using growth hormone (GH) to accelerate their growth respond to this treatment with a variable efficacy. The causes of this individual variability are multifactorial and could involve epigenetics. Quantifying the impact of epigenetic variation on response to treatments is an emerging challenge. Here we show that methylation of a cluster of CGs located within the P2 promoter of the insulin-like growth factor 1 (IGF1) gene, notably CG-137, is inversely closely correlated with the response of growth and circulating IGF1 to GH administration. For example, variability in CG-137 methylation contributes 25% to variance of growth response to GH. Methylation of CGs in the P2 promoter is negatively associated with the increased transcriptional activity of P2 promoter in patients' mononuclear blood cells following GH administration. Our observation indicates that epigenetics is a major determinant of GH signaling (physiology) and of individual responsiveness to GH treatment (pharmacoepigenetics).

Three common intronic variants in the maternal and fetal thiamine pyrophosphokinase gene (TPK1) are associated with birth weight.

Extreme variations in birth weight increase immediate postnatal mortality and morbidity, and are also associated with the predisposition to metabolic diseases in late adulthood. Birth weight in humans is influenced by yet unknown genetic factors. Since the 7q34-q35 region showed linkage with birth weight in a recent human genome scan (p = 8.10(-5)), this study investigated the TPK1 (thiamine pyrophosphokinase) gene locus, located in 7q34-36. Having found no coding variants in the TPK1 gene, we genotyped 43 non coding SNPs spanning a region of 420kb, and used the QTDT method to test their association with birth weight in 964 individuals from 220 families of European ancestry. Family-based tests detected association of 8 SNPs with birth weight (p<0.008), but after correction for multiple tests only rs228581 C/T (p = 0.03), rs228582 A/G (p = 0.04) and rs228584 C/T (p = 0.03) were still associated with birth weight, as well as their T-A-T haplotype (p = 0.03). In addition, we found an association between maternal rs228584 genotype and offspring birth weight (p = 0.027). These observations suggest that genomic variations in the fetal and maternal TPK1 gene could contribute to the variability of birth weight in normal humans.

'Non-Mendelian' genetics of fetal growth.

Mendelian genetics showed that a few mutated genes, or errors in parental imprinting, can lead to major phenotypic changes (diseases) in pre-natal growth. Mendelian genetics, however, do not explain the individual subtle variability of size at birth within the normal range. Fetal growth is a complex multifactorial, multigenic trait made of various sub-traits, such as body mass, fat and muscle, brain mass, head circumference, skeletal growth of the spine and limbs. It is likely that multiple genetic factors and genomic variants are responsible for the variations of these sub-traits. A study has been launched to investigate the genetics of the variation of human birth weight, with the ultimate aim of identifying genomic variations that are within or near certain genes and are associated with variations of human height and weight at birth.

A new biodegradable elastin-fibrin material; its use in urological, digestive and cardiovascular surgery.

A new original artificial connective matrix mainly made of elastin and fibrin-like product is used to reinforce damaged tissues and to close and restore a loss of substance in several domains of surgery: all sites in the digestive system and urinary tract; besides, it can substitute for the pericardium in iterative heart operations. In all cases, the original tissue is restored ad integrum while the biodegradable material disappears completely, without any complications.

Split-mode unstable resonator.

A novel class of unstable resonators is described in which the mode spatial distribution is altered within the resonator by a prism or axicon. In the particular configuration studied in this work, the resonator beam is separated into two halves by an intracavity reflecting prism. The conditions under which the two halves of the resonator become phase locked to form a coherent mode are studied experimentally and discussed in terms of laser injection locking.

Confirmation of an Electron Avalanche Causing Laser-induced Bulk Damage at 1.06 microm.

Measurements have been made on intrinsic optical bulk breakdown in ten alkali halides at 1.06 microm and in one at 0.69 microm. By comparing the results to previously reported experiments conducted at 10.6 microm and at direct current, it has been possible to identify the damage mechanism as electron avalanche breakdown. Self-focusing has been controlled by restricting the probe powers to well below the critical powers for catastrophic self-focusing, and damage from inclusions has been distinguished from intrinsic damage. Implications of this work for surface damage studies are explored.