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La pandémie de COVID-19 modifie profondément l’organisation et l’accès aux soins, en particulier pour les pathologies néoplasiques péritonéales, dont la prise en charge curative mobilise des moyens importants en personnel, bloc opératoire et réanimation. Les groupes BIG-RENAPE et RENAPE proposent des pistes de réflexion et de priorisation pour leur prise en charge. Un renforcement des critères habituels de sélection est nécessaire pour une prise en charge à visée curative : patients jeunes, avec peu de co-morbidités et une extension péritonéale limitée. Il est souhaitable de prioriser les pathologies pour lesquelles la chirurgie de cytoréduction associée ou non à une chimiohyperthermie intrapéritonéale (CHIP) est le traitement de référence et celles pour lesquelles la chimiothérapie systémique ne peut être une alternative temporaire ou prolongée : pseudomyxomes péritonéaux ; mésothéliomes péritonéaux malins résécables ; métastases péritonéales d’origine colorectale si résécables, non répondeuses à la chimiothérapie systémique et/ou après 12 cures, carcinoses ovariennes en 1reintention si résécables et limitées ou en situation intervallaire après un maximum de 6 cycles de chimiothérapie systémique. L’adjonction d’une CHIP devra être discutée au cas par cas, en centre expert. La priorisation des indications devra prendre en considération les conditions locales et la phase de la période épidémique pour permettre une prise en charge péri-opératoire optimale.

Alternative splicing as a mean to control gene expression and diversify function is suspected to considerably influence drug response and clearance. We report the quantitative expression profiles of the human UGT genes including alternatively spliced variants not previously annotated established by deep RNA-sequencing in tissues of pharmacological importance. We reveal a comprehensive quantification of the alternative UGT transcriptome that differ across tissues and among individuals. Alternative transcripts that comprise novel in-frame sequences associated or not with truncations of the 5'- and/or 3'- termini, significantly contribute to the total expression levels of each UGT1 and UGT2 gene averaging 21% in normal tissues, with expression of UGT2 variants surpassing those of UGT1. Quantitative data expose preferential tissue expression patterns and remodeling in favor of alternative variants upon tumorigenesis. These complex alternative splicing programs have the strong potential to contribute to interindividual variability in drug metabolism in addition to diversify the UGT proteome.

A comprehensive view of the human UDP-glucuronosyltransferase (UGT)transcriptome is a prerequisite to the establishment of an individual’s UGT metabolic glucuronidation signature. Here, we uncover the transcriptome landscape of the 10 human UGTgene loci in normal and tumoral metabolic tissues by targeted RNA next-generation sequencing. Alignment on the human hg19 reference genome identifies 234 novel exon–exon junctions. We recover all previously known UGT1and UGT2enzyme-coding transcripts and identify over 130 structurally and functionally diverse novel UGTvariants. We further expose a revised genomic structure of UGTloci and provide a comprehensive repertoire of transcripts for each UGTgene. Data also uncover a remodelling of the UGTtranscriptome occurring in a tissue- and tumor-specific manner. The complex alternative splicing program regulating UGTexpression and protein functions is likely critical in determining detoxification capacity of an organ and stress-related responses, with significant impact on drug responses and diseases.

Two loci independently implicated in T-and B-lymphocyte neoplasia are shown to be equivalent. The Mis-1 locus is a common proviral integration site in retrovirally induced rat T lymphomas, while the pvt-1 locus on murine chromosome 15 frequently translocates to the kappa locus in plasmacytomas bearing 6;15 translocations. By comparing cloned sequences, we show that pvt-1 is the murine homolog of Mis-1.

Ahi-1 has previously been identified as a common helper provirus integration site on mouse Chromosome (Chr) 10 in 16% of Abelson pre-B-cell lymphomas and shown to be closely linked to the Myb protooncogene. By using long-range restriction mapping, we have mapped the Myb and Ahi-1 regions within a 120-kbp DNA fragment. The Ahi-1 region is located approximately 35 kbp downstream of the Myb gene. A further comfirmation of this finding was obtained by screening a mouse YAC library. The three positive clones obtained contained both the Myb and Ahi-1 gene sequences. To test whether provirus integration in the Ahi-1 region enhances the expression of Myb by a cis-acting mechanism, we have also examined Myb gene expression in A-MuLV-induced pre-B-lymphomas. Our data have revealed that there is no clear evidence for such activation in the tumors we have tested, indicating that provirus insertion in the Ahi-1 region is activating a novel gene, apparently involved in tumor formation.

Acute myeloblastic leukemia (AML) blasts have been shown to produce a variety of cytokines in culture such as interleukin-1 (IL-1), IL-6, granulocyte-, macrophage-, and granulocyte-macrophage colony- stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF alpha). Using two sensitive and specific enzyme-linked immunosorbent assays for IL-1 beta and GM-CSF, we document in the present study that the production of the two cytokines by AML blasts in culture is coordinated. First, we observe a striking correlation between the levels of GM-CSF and IL-1 beta released by the cells. Thus, a high production of IL-1 beta is always concordant with a high production of GM-CSF and, conversely, low production of IL-1 beta is concordant with low levels of GM-CSF. Second, neutralization of intrinsic IL-1 using antibodies that are specific for IL-1 alpha and -1 beta suppresses the release of GM-CSF by the cells. Third, neutralization of the endogenous source of IL-1 also results in an abrogation of GM-CSF mRNA. Fourth, the production of both IL-1 beta and GM-CSF is up-regulated by exposing AML blasts to an exogenous source of IL-1, suggesting a positive regulation of autocrine growth factor production. Taken together, our results indicate that GM-CSF production by AML blasts is mediated by endogenously produced IL-1. Both IL-1 beta and -1 alpha are produced by AML blasts, although IL-1 beta appears to be more abundant. Spontaneous colony formation by AML blasts is abrogated by the addition of neutralizing antibodies against IL-1 beta and GM-CSF, whereas each antibody alone has little effect on blast proliferation. Taken together, our results are consistent with the view that the production of IL-1 beta by AML blasts supports autocrine growth in culture, through induction of CSFs or other cytokines that stimulate blast proliferation.

We have identified the sites of transcription of the apolipoprotein D (apoD) gene in the rabbit by in situ hybridization. We show here for the first time that 1) apoD mRNA production does not correlate with the sites of steroid hormone production in adrenal glands nor male genital tissues; and 2) the expression of the apoD gene is clearly higher in white than in gray matter throughout the central nervous system (CNS). Specifically, apoD mRNA was abundant near blood vessels and was expressed mostly in fibroblast-like cells, in particular in the testis, the efferent ducts, the ductus epididymis, the lung, and the subarachnoid space of the CNS. Other positive cell types were endothelial cells of adrenal sinusoidal capillaries and glial cells of the CNS. We detected apoD mRNA in both the adrenal cortex and medulla. White but not gray matter showed high levels of apoD mRNA throughout both the rabbit CNS and in human brain. The red pulp of spleen showed a strong hybridization. In prepubertal rabbits apoD mRNA levels were moderate in both testis and epididymis. Epididymal but not testicular expression increased with the onset of puberty and epididymal levels always exceeded those of the testes in animals showing spermatogenesis. Thus, the variation in levels of apoD mRNA among organs in vivo, that we and others have previously reported, can be explained by transcription being not only characteristic of cell type, with a few common cell types producing in each organ, but transcription also varied among cells of the same lineage.

Acute myeloblastic leukemia (AML) blasts have been shown to produce a variety of cytokines in culture such as interleukin-1 (IL-1), IL-6, granulocyte-, macrophage-, and granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-a (TNFa). Using two sensitive and specific enzyme-linked immunosorbent assays for IL-1β and GM-CSF, we document in the present study that the production of the two cytokines by AML blasts in culture is coordinated. First, we observe a striking correlation between the levels of GM-CSF and IL-1/β released by the cells. Thus, a high production of IL-1/β is always concordant with a high production of GM-CSF and, conversely, low production of IL-1/β is concordant with low levels of GM-CSF. Second, neutralization of intrinsic IL-1 using antibodies that are specific for IL-1 α and -1β suppresses the release of GM-CSF by the cells. Third, neutralization of the endogenous source of IL-1 also results in an abrogation of GM-CSF mRNA. Fourth, the production of both IL-1/β and GM-CSF is up-regulated by exposing AML blasts to an exogenous source of IL-1, suggesting a positive regulation of autocrine growth factor production. Taken together, our results indicate that GM-CSF production by AML blasts is mediated by endogenously produced IL-1. Both IL-1β and -lα are produced by AML blasts, although IL-1β appears to be more abundant. Spontaneous colony formation by AML blasts is abrogated by the addition of neutralizing antibodies against IL-1β and GM-CSF, whereas each antibody alone has little effect on blast proliferation. Taken together, our results are consistent with the view that the production of IL-1β by AML blasts supports autocrine growth in culture, through induction of CSFs or other cytokines that stimulate blast proliferation. © 1990 by The American Society of Hematology.

The spectroscopic and photophysical characterization of rhodamine 123 (dye 1), 4,5-dibromorhodamine methyl ester (dye 2) and 4,5-dibromorhodamine n-butyl ester (dye 3) are reported in homogeneous media like water and some alcohols and also in microheterogeneous media; anionic sodium dodecylsulfate (SDS), cationic cetyltrimethylammonium bromide (CTAB) and neutral triton X-100 (TX) micelles. The selective biodistribution of these ionic drugs in tissues and membranes strongly influence their photosentisizing properties which have been part of our earlier studies. Results suggest that the hydrogen bonding capability of the amino end group lone pair of these dyes dominates in water. All these dyes interact with anionic SDS micelles. The interaction is mainly electrostatic in nature. At low SDs concentrations (below c.m.c.), dye-SDS aggregate formation takes place. But above c.m.c. only the monomeric dye form is observed. The penetration of dye 3 in SDS is a little less compared to dyes 1 and 2. Dyes 2 and 3 show a finite interaction with CTAB micelle unlike dye 1. With neutral TX micelles all the dyes form strong complexes. The fluorescence quantum yield (ΦF) of these three dyes in TX is lower. In time-resolved fluorescence experiments, two lifetimes are observed. The effects of the TX concentration on the fluorescence decay are measured. The decay associated spectra of dye 2 in TX are obtained by global compartmental analysis. The dye-surfactant interaction mechanisms are also discussed.

The nondefective Moloney murine leukemia virus (MuLV) induces clonal or oligoclonal T-cell tumors in mice or rats. The proviruses of these nondefective MuLVs have been shown to act as insertion mutagens most frequently activating an adjacent cellular gene involved in cell growth control. Mutations by provirus insertions, recognized as common provirus integration sites, have been instrumental in identifying novel cellular genes involved in tumor formation. We have searched for new common provirus integration sites in Moloney MuLV-induced thymomas. Using cellular sequences flanking a provirus cloned from one of these tumors, we found one region, designated Mis-2, which was the target of provirus integration in a low (3%) percentage of these tumors. Mis-2 was mapped on mouse chromosome 10, approximately 160 kbp downstream of myb. The Mis-2 region may contain a novel gene involved in tumor development.

We have previously identified a region of genomic DNA which constitutes the site of frequent provirus integration in rat thymomas induced by Moloney murine leukemia virus (Lemay and Jolicoeur, Proc. Natl. Acad. Sci. USA 81:38-42, 1984). This genetic locus is now designated Mis-1 (Moloney integration site). Cellular sequences homologous to Mis-1 are present in mouse DNA. Using a series of hamster-mouse somatic cell hybrids, we mapped the Mis-1 locus to mouse chromosome 15. Frequent chromosome 15 aberrations have been described in mouse thymomas. Mis-1 represents a putative new oncogene which might be involved in the initiation or maintenance or both of these neoplasms.

ABSTRACTWe describe here what is, to the best of our knowledge, the third reported case of severe thrombocytopenia associated with acute hepatitis E virus infection. The patient was a 72-year-old French woman. It seems likely that the cause of the thrombocytopenia was acute hepatitis E virus infection, possibly occurring via an immune mechanism. No complications were noted, in contrast to the two previous reports.

La pathologie herniaire représente une des premières causes de chirurgie. Pour les patients asymptomatiques, une prise en charge chirurgicale est discutable. L’objectif de cette étude était d’évaluer les pratiques d’une large population de chirurgiens digestifs devant une hernie non symptomatique.

La chirurgie de cytoréduction (CCR) complète est le seul traitement potentiellement curatif des patients atteints de métastases péritonéales du cancer colorectal (MPCC).

Depuis 2012, la déclaration obligatoire (DO) des mésothéliomes par les médecins (cliniciens, pathologistes) à l’Agence régionale de santé vise à renforcer la surveillance des mésothéliomes (tous sites anatomiques, territoire national) et à améliorer la connaissance des expositions, notamment environnementales à l’amiante. Pour cela, la DO est complétée depuis 2014 par des enquêtes d’exposition professionnelle et environnementale dans 9 régions pilotes. Après plus de 3ans de fonctionnement, l’Institut de veille sanitaire fait un bilan du dispositif de DO et des enquêtes d’exposition.