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The prognosis of patients with advanced soft-tissue sarcomas (STS) remains dismal, and systemic therapeutic options are limited. Early phase trials are becoming increasingly safe and effective. This study aimed to identify the prognostic factors for progression-free survival (PFS).This retrospective analysis included all STS patients participating in early phase trials at Gustave Roussy and Léon Bérard between 1 January 2012 and 31 December 2020.Overall, 199 patients accounted for 214 inclusions in advanced STS. The most frequent histotypes were well-differentiated/dedifferentiated liposarcomas (n = 55), leiomyosarcomas (n = 53), synovial sarcomas (n = 22), undifferentiated pleomorphic sarcomas (n = 15), angiosarcomas (n = 12), and myxoid liposarcomas (n = 10). The median PFS was 2.8 months (95% confidence interval 2.7-4.1 months). The median PFS in the first, second, and later lines was 8.3, 5.4, and 2.6 months, respectively (P = 0.00015). The median PFS was 2.8 months in case of molecular screening, 4.1 months in case of histology-driven screening, and 1.6 months (P = 0.00014) in the absence of either screening modalities. In univariate analysis, histotype (P = 0.026), complex genomics (P = 0.008), number of prior lines (P0.001), prior anthracyclines (P0.001), number of metastatic sites (P = 0.003), liver metastasis (P0.001), lung metastasis (P0.001), absence of molecular or histology-driven screening (P0.001), first-in-human trials (P0.001), dose-escalation cohorts (P = 0.011), and Royal Marsden Hospital (RMH) score1 (P0.001) were significantly associated with shorter PFS. In multivariate analysis, independent prognostic factors for shorter PFS were myxoid liposarcoma (P = 0.031), ≥2 prior lines of treatment (P = 0.033), liver metastasis (P = 0.007), and RMH score2 (P = 0.006). Factors associated with improved PFS were leiomyosarcomas (P = 0.010), molecular screening (P = 0.025), and histology-driven screening (P = 0.010). The median overall survival rates were 36.3, 12.6, and 9.2 months in the first, second, and later lines, respectively (P = 0.0067). The grade 3-4 toxicity rate was 36%.Early phase trials provide an active therapeutic option for STS, even in first-line settings. Molecular screening and histology-driven trials further improve the clinical benefit.

Introduction C. difficile est responsable de 15 a 25 % des diarrhees post-antibiotiques et de plus de 95 % des cas de colites pseudo-membraneuses (CPM). L’infection a C. difficile (ICD) peut varier de la forme de portage asymptomatique a une CPM pouvant se compliquer de perforation colique ou de megacolon toxique. A l’admission a l’hopital, le taux de colonisation asymptomatique est estime entre 1,4 % et 21 %. L’objectif de cette etude etait d’evaluer les facteurs associes a une colonisation asymptomatique a l’admission dans un centre hospitalo-universitaire (CHU). Materiels et methodes Une etude de cohorte prospective a ete menee dans les services suivants d’un CHU : reanimation (n = 3), geriatrie (n = 3) et nephrologie (n = 1). Des echantillons de selles ont ete preleves dans les 48 heures suivant l’admission dans ces services. Un test immunochromatographique combine (Alere®) et une culture anaerobie ont ete realises systematiquement. Les facteurs associes a la colonisation par C. difficile a l’admission ont ete identifies par une regression logistique multivariee. Les analyses ont ete realisees avec le logiciel SPSS® 19. Resultats Au total, 539 patients ont ete inclus entre mars 2017 et mars 2018. La moyenne d’âge etait de 71,6 ans (min–max : 18–99) et 53 % (n = 285) etaient des hommes. La plupart des patients inclus (n = 500 [92,8 %]) souffraient d’au moins une pathologie sous-jacente. La duree moyenne de sejour etait de 23,7 jours (min–max : 2–252). Un prelevement de selles a ete realise a l’admission chez 61,3/100 patients admis. C. difficile a ete isole chez 20 patients asymptomatiques (pas de diarrhee) (3,7 % ; 12/20 (60 %) avaient une souche toxinogene). L’analyse multivariee a montre que les facteurs independamment associes a la colonisation par une souche toxinogene (reference : patients avec une recherche negative du C. difficile) etaient : le sexe masculin [OR : 21,6 (IC95 % :1,4–329,7) ; p = 0,03], l’osteoporose [OR : 12,4 (IC95 % :1,2–131,5) ; p = 0,04], l’hospitalisation dans les 3 derniers mois [OR : 6,4 (IC95 % :1,4–28,6) ; p = 0,02], la nutrition parenterale dans les 30 derniers jours [OR : 8,9 (IC95 % :1,4–57,9) ; p = 0,02], et la prise dans les 60 derniers jours d’amoxicilline [OR :10,0 (IC95 % :1,7–57,9) ; p = 0,01], de C4G [OR : 13,1 (IC95 % :1,1–158,8) ; p = 0,04] ou de metronidazole [OR : 5,5 (IC95 % :1,4–22,1) ; p = 0,02]. Conclusion Les porteurs asymptomatiques constituent un reservoir de transmission du germe mais les recommandations actuelles ne preconisent pas de prise en charge specifique de ces patients. Les resultats de cette etude montrent que des facteurs de risque de portage asymptomatique sont identifiables a l’admission ce qui pourrait orienter vers une politique de depistage cible chez ces patients.

International audience; Transplant recipients are at risk of developing Legionnaires' disease (LD) because of impaired cellular immunity. Here, we describe a renal transplant recipient who developed LD at least 10 days after hospital admission and transplantation. The hospital water network was initially suspected, but further testing determined that the probable source was the patient's domestic water supply. Our report also suggests that the patient's immunosuppressed state may have switched potential colonization to pneumonia.

International audience; OBJECTIVES: Legionella pneumophila serogroup 1 (Lp1) sequence type 47 is the leading cause of legionellosis in north-western Europe, but, surprisingly, it is rarely isolated from environmental samples. Comparative genomics was applied to develop a PCR assay and to better understand the evolution of this strain. METHODS: Comparative analysis of 36 genomes representative of the Lp species was used to identify specific PCR targets, which were then evaluated in silico on 545 sequenced genomes and in~vitro on 436 Legionella strains, 106 respiratory samples, and three environmental samples from proven ST47 sources. Phylogenetic analyses were performed to understand the evolution of ST47. RESULTS: The gene LPO\₁073 was characterized as being 100% conserved in all 129 ST47 genomes analysed. A real-time PCR designed to detect LPO\₁073 was positive for all 110 ST47 strains tested and agreed with culture and typing results previously obtained for 106 respiratory samples. The three environmental samples were also positive. Surprisingly, 26 of the 44 ST109 strains tested among 342 non-ST47 strains scored positive for LPO\₁073. SNP-based phylogenetic analysis was undertaken to understand this result: the PCR-positive ST109 genomes were almost identical to ST47 genomes, with the exception of a recombined region probably acquired by ST47 from a ST62(-like) strain. CONCLUSION: The genomic analysis allowed the design of a highly specific PCR assay for rapid detection of ST47 strains. Furthermore, it allowed us to uncover the evolution of ST47 strains from ST109 by homologous recombination with ST62. We hypothesize that this recombination generated the leading cause of legionellosis in north-western Europe.

The contamination of aerosols by washbasin water colonized by Legionella in a hospital was evaluated. Aerosol samples were collected by two impingement technologies. Legionella was never detected by culture in all the (aerosol) samples. However, 45% (18/40) of aerosol samples were positive for Legionella spp. by polymerase chain reaction, with measurable concentrations in 10% of samples (4/40). Moreover, immunoassay detected Legionella pneumophila serogroup 1 and L. anisa, and potentially viable bacteria were seen on viability testing. These data suggest that colonized hospital washbasins could represent risks of exposure to Legionella aerosol inhalation, especially by immunocompromised patients.

Resume Objectifs Description des cas confirmes de grippe A(H1N1)pdm09 admis en reanimation dans un centre hospitalo-universitaire et identification des facteurs de gravite. Patients et methodes Durant la pandemie grippale A(H1N1)pdm09, une etude prospective realisee dans un centre hospitalo-universitaire a permis de decrire et comparer les cas de grippe A(H1N1)pdm09 confirmes et definis comme graves (hospitalisation en reanimation) aux cas de moindre gravite (absence d’hospitalisation en reanimation). Resultats Parmi les 69 cas inclus, 36 (52 %) etaient âges entre 15 et 44 ans. Au total, 16 (23 %) cas ont ete definis comme graves, dix (63 %) etant âges entre 45 et 64 ans. Les facteurs independants associes a la gravite etaient les antecedents de pathologies cardiaques, le tabagisme et l’obesite. Conclusions Ce travail confirme l’importance d’identifier et de proteger les patients a risque d’aggravation.

Resume Bien que rare, les infections associees aux chambres a catheter implantables (CCI) restent une des complications les plus frequentes apres la thrombose et elles sont a l’origine d’un pourcentage eleve de retraits. En France, seul le referentiel publie par l’Anaes en 2000 propose des recommandations qui specifiquement de la prevention du risque infectieux associe aux CCI. Apres un rappel des donnees epidemiologiques, cette mise au point a pour objectif de propos une synthese des travaux scientifiques utilises pour l’elaboration de recommandations professionnelles par consensus formalise d’experts sous l’egide de la Societe francaise d’hygiene hospitaliere (SF2H).

Le cancer du sein est la deuxieme cause demetastases cerebrales. Chez les patientes ayant un cancer du sein HER2+, l’incidence de ces metastases cerebrales s’eleve a 40 %. Autant l’arrivee des therapies anti-HER2 a permis un meilleur controle de la maladie metastatique extracerebrale, autant il reste des progres therapeutiques a realiser pour le controle de ces metastases cerebrales. Actuellement, les voies de recherche portent sur les associations radiochimiotherapies, les associations anti-HER2-chimiotherapie et plus particulierement l’association lapatinib-capecitabine ou encore l’administration intrathecale d’herceptine.

The aim of this study was to investigate the risk factors associated with CTX-M-producing Escherichia coli strains isolated from infected or colonized patients. From 191 clinical samples, a case–control study was designed. From January 2005 to December 2007, 98 hospitalized patients infected or colonized with CTX-M-producing E. coli were included in the study. They were matched 1 : 1 with controls that had a non-CTX-M-producing E. coli infection on the basis of the site of sample, the unit of hospitalization and the time at risk. The rate of CTX-M-producing E. coli among those producing extended spectrum β-lactamases was always ≥90% from 2005 to 2008. All strains were susceptible to carbapenems. However, we observed a high rate of co-resistance to ciprofloxacin (61%), sulphonamides (86%) and gentamicin (34%). Significant risk factors identified by multivariate analysis were recurrent infections (OR = 2.93), presence of artificial nutrition (OR = 3.99), and recent exposure to quinolones (OR = 4.39), third- or fourth-generation cephalosporin (OR = 3.49) and the combination of both antibiotic classes (OR = 5.50). This report highlights the dramatic increase of CTX-M-producing E. coli and the need for changes in the use of antimicrobial drugs and in infection control measures to manage this major health concern.

Neuroendocrine small cell carcinoma of the bladder is a rare and aggressive cancer with a very pejorative behavior. Neuroendocrine small cell carcinoma of bladder is a histological entity with special characteristics, rapidly aggressive and metastatic and with a poor prognosis. Because it is rare, there is no consensus to date. Its management should be multidisciplinary, involving surgery, chemotherapy and radiotherapy. We report the case of an 84-year-old patient with neuroendocrine small cell carcinoma of the bladder, treated by neoadjuvant chemotherapy followed by a combined chemoradiotherapy. A review of the literature on this topic is also presented.

Culture media performance is a critical factor in the isolation of Legionellae from respiratory samples. We showed that BMPA and MWY media yielded significantly higher isolation rates than GVPC and BCYE media in regard to performance with samples that harbored low Legionella inocula and high contamination levels.

International audience; In France, approximately 1200 cases of Legionnaires disease (LD) are reported annually, and isolates are available for approximately 20% of cases identified since 2000. All Legionella pneumophila serogroup 1 (sg1) isolates are characterized by sequence-based typing at the National Reference Centre. LD cases caused by L.~pneumophila sg1 reported from 2008 through 2012 were considered for the study. Our study objective was to describe cases according to their sequence type (ST). We also constructed multivariable modified Poisson regression models to estimate the incidence rate ratio (IRR) and to identify characteristics potentially associated with ST23 clones compared to ST1 and ST47 clones. We studied 1192 patients infected by ST1 (n~= 109), ST23 (n~= 236), ST47 (n~= 123) or other STs (n~= 724). The geographic distribution of the ST23 cases across the country was significantly different compared to other ST groups. This genotype was significantly associated with the absence of corticosteroid therapy compared to ST1 (IRR~= 0.56; p 0.016). Concerning exposure, the ST23 genotype was significantly less associated with hospital-acquired infections compared to ST1 (IRR~= 0.32; p 0.001), but it was more associated with infections acquired in hospitals and elderly settings compared with ST47. Finally, the ST23 genotype was less frequently associated with travel than other STs. Despite the large number of cases of ST23 infection, we did not identify any characteristics specific to this ST. However, we identified independent associations between ST1 and nosocomial transmission and steroid therapy. These findings should encourage further exploration, especially in terms of environmental diffusion, strain virulence and host factors.

Epstein-Barr virus (EBV) is known to establish latent infections in B-lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV-associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were naïve for EBV before the transplantation, that they developed a post-transplant lymphoproliferative disorder before the diagnosis of EBV-PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV-PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV-PTSMT are discussed based on a comprehensive review of the literature.

Platypus beetles can attack apparently healthy or more or less decaying trees, causing economic damage to the timber by digging galleries in the wood or killing the trees. They transport the spores of Ambrosia fungi or others (Graphium spp) inside specialized prothoracic mycangia of the female. These mycangia are linked with several unusual glandular cells. Their ultrastructural study shows the presence of a large bundle of interlaced microtubular structures going through the cuticle from the cavity of the glandular cell to the spheroidal cavity containing the spores. These glandular cells show the characteristics of non-proteic secreting cells. Another type of glandular unit (type III) exists all round the mycangial cavities. The possible role of all these structures in helping to establish a mutualistic relationship between the beetle and fungi is discussed.

To evaluate the contribution of the setaceous membrane of the worker to the defensive behaviour of a bee colony, we studied its fine structure and the effect of alarm pheromones present on the membrane surface on the reaction of guards. Groups of guards at the hive entrances displayed defence behaviour when stimulated with volatiles from the setaceous membranes. Transmission electron microscopy sections of the setaceous membrane did not reveal any structure characteristic of an exocrine gland, in contrast to the sting sheaths or the Koschewnikow glands. Both surfaces of the membrane are abundantly covered with setae, which can considerably increase the general surface of the membrane and thus are suited for a quick discharge of alarm pheromones. The setaceous membrane serves only as a platform to release the alarm pheromones originating from the glandular part of the sting sheaths and the Koschewnikow glands.

Objectifs Decouverte d’une lesion secondaire atypique musculaire du grand adducteur droit au decours d’une TEP/TDM au 18F-FDG realisee dans le suivi d’un GIST grelique CD 117 positif avec mutation de l’exon 11 de KIT. Materiels et methodes Patiente de 66 ans, suivie pour un GIST de l’intestin grele depuis 2006, traitee initialement par chirurgie. En 2009, apparition de lesions secondaires hepatiques confirmees par biopsie. Mise en place d’un traitement par imatinib, puis hepatectomie partielle en 2012. Poursuite du traitement par imatinib et de la surveillance en postoperatoire. L’acquisition TEP/TDM standard, du sommet du crâne au tiers superieur de cuisses, a ete realisee 1 heure apres injection de 316 MBq de 18F-FDG. Resultats L’examen TEP realise en 2015 montre une recidive multifocale intra-abdominale hypermetabolique. De plus, apparition d’une adenopathie sous carenaire hypermetabolique sans lesion parenchymateuse pulmonaire sous-jacente (SUVmax 6,1) et d’un hypermetabolisme intense en regard d’une lesion hypodense du grand adducteur de la cuisse droite (SUVmax 6,2). Devant la decouverte de ces localisations d’allure secondaire ne correspondant pas au mode de diffusion habituel des GIST, des prelevements histologiques ont ete realises sur les deux lesions extra-abdominales. Les analyses histologiques, cytologiques et moleculaires (mutation de l’exon 11 de KIT et apparition d’une mutation de l’exon 17 de KIT de resistance a l’imatinib) confirment le diagnostic de lesion secondaire du GIST du grele connu. Conclusions Les localisations secondaires de GIST en dehors de la cavite peritoneale et du foie sont exceptionnelles lors du diagnostic initial et restent rares au cours du suivi : seuls quelques cas ont ete decrits dans la litterature. Une confirmation histologique, cytologique et moleculaire est indiquee dans ces rares cas. Nous rapportons ici un nouveau cas.

This paper reports on the fine structure of the Nassanov glands, in relation with their capacity to secrete both volatile and protein compounds. The protein fraction seems to enhance the attractiveness of the volatile fraction.

To study the behavior of the toxins E and A destruxin in biological media, a method was developed with direct injection on to a liquid chromatographic (LC) column. Either slightly lipophilic C 1 and C 4 “wide-pore” packings or the column-switching approach with a guard column were used. To confirm the results of the direct LC analysis, a “classical approach” with pretreatment prior to injection on to a C 8 packed column was also developed. Further, parallel fast atom bombardment MS monitoring in the negative-ion mode was carried out on the same biological samples, to obtain complementary information on the destruxin metabolism in locusts. Thus, the behaviours of E and A destruxin were examined in vivo in different organs of locusts. For E destruxin, several detoxication processes could be observed, such as hydrolysis and conjugation with glutathione.

To evaluate the contribution of the sting sheaths of the worker to the defensive behaviour of a bee colony, we studied their fine structure and the effect of their secretions on the reaction of guards. (1) The structure of the proximal part of the sting sheath integument has all the characteristics of a primitive exocrine gland: porous cuticle with enlarged pore canals and epicuticular pores, and hypertrophied epithelial cells secreting an electron dense material. The non-volatile part of the secretory product embedded the setae of the sheaths. (2) Individual recipient guards in the laboratory and as a group at hive entrances in a beeyard displayed defence behaviour only when stimulated with either sting sheaths or with setaceous membrane, but not with any other gland or organ. Enhanced defensive reaction of guards has been observed when a venom gland or Koschewnikow's glands, are added to either sting sheaths or to setaceous membrane. (3) We demonstrate for the first time that the sting sheaths have the structure of an exocrine gland and that their secretions induce defensive behaviour in guards.

1. 1. The wax moth, Galleria metionella enters larval diapause when 1-day-old last instar larvae are transferred from an optimal rearing temperature of 30 to 18°C. In the haemolymph of diapausing larvae very low ecdysteroid titres exist which are due to synthetic inactivity of the prothoracic glands and not due to a reduction in prothoracic gland cell numbers. Ultrastructural analysis of the prothoracic glands taken from diapause-committed 8-day-old last instar larvae, show all the signs of inactivity as far as the development of the endoplasmic reticulum and mitochondrial system are concerned. Whereas in the same age last instar non-diapausing larvae, the glands are extremely active as judged by their ultrastructure. 2. 2. Paraldehyde-fuchsin staining and ultrastructural studies have revealed that in diapause-committed 8-day-old last instar larvae of Galleria mellonella, neurosecretory cells of the protocerebrum accumulate the neurosecretory vesicles in their perikaria. The protocerebral cells of control (non-diapausing) larvae of the same age contain only a small amount of neurosecretory vesicles. 3. 3. The corpora allata of diapause-committed larvae seems to be inactive despite the high titre of juvenile hormone found in their haemolymph. The endoplasmic reticulum and mitochondrial system, organellae involved in the juvenile hormone biosynthesis, are reduced. 4. 4. The possible mechanism controlling larval diapause of Galleria mellonella is discussed.

Experiments in vitro have shown that 20-hydroxyecdysone (at a concentration of 0.2 and 2 μM and after 12 and 24 hr of incubation) is able to induce the precocious deposition of chorion materials by the follicular epithelium of young oocytes of the cockroach Blattella germanica. Since previous studies had shown that 20-hydroxyecdysone levels in B. germanica ovaries increase with oocyte maturation to reach a peak just before oviposition, we therefore hypothesize that ovarian ecdysteroids trigger Choriogenesis in this species through an autocrine action.

Multidimensional chromatographies (MDC) implying either a single column with an unique packing designed for providing several separation modes such as internal surface reversed-phase (ISRP), or C1 large pores particles, or multi-column switching technique using the previous supports as guard columns, allow fast and easy direct monitoring of pesticides into plant or animal biological media. In such a way, the comparative study of the agricultural fungicide cymoxanil in two strains of Botrytis cinerea of different sensitivities gave concordant conclusions with the previous work using radiolabelled cymoxanil and TLC. Moreover, as a comparison, a study of the metabolism of this xenobiotic was also followed in animal biological fluids likely to contain peptidases. In locust or lobster haemolymph, an unusual isomerization into a cyclic compound was thus demonstrated accompanying the classical peptidase-depending metabolism generally observed in plants. The same chromatographic approaches were tested and compared for monitoring the metabolism of the natural insecticide toxin E-destruxin in insects. A detoxication process leading to the less toxic E-diol destruxin was evidenced in the organs or haemolymph of the locust Locusta migratoria chosen as a model of non-target insects.

In addition to glial cells, intrinsic glandular cells and ordinary axons, the corpora cardiaca of Blattella germanica (L.) (Dictyoptera : Blattellidae) contain 4 types of neurosecretory fibers originating from the brain (types 1, 2, 3, and 4), which can be recognized on the basis of the size, form, and electron density of their neurosecretory granules. A comparative ultrastructural study of the corpora cardiaca from normal females and from dopamine-treated (1 μg) females has been carried out at different stages within the first ovarian cycle (freshly emerged: day 0; 2-day-old: pre-vitellogenesis; 4-day-old: beginning of vitellogenesis; 6-day-old: full vitellogenesis; 8-day-old: post-vitellogenesis, period of ootheca transport). Quantitative data on the exocytotic configurations observed in each type of fiber (1–4) have led to the following conclusions: (a) the exocytotic configurations in control specimens are too infrequent to prompt any inference about the dynamics of neurosecretion release in the different types of fibers; (b) dopamine treatment induces a stimulation of the exocytotis phenomenon, whose extent depends on the specimen age and on the type of fiber. Therefore, on days 2 and 6, dopamine: preferentially stimulates neurosecretion release in the fibers of types 3 and 4 respectively.

The recent progress of the biology of the locally aggressive sarcomas of soft tissues and related connective tissue tumors enabled to reclassify molecular and histological entities of the disease. Six subgroups of sarcomas are identified with specific molecular alterations, the targeted treatments of which are the object of this article: 1) sarcomas with specific translocations with fusion oncogenes (DFSP, PVNS); 2) sarcomas with tyrosine kinase mutations (KIT in GIST); 3) tumors with deletion of tumor suppressor genes (TSC in the PEComes, NF1 involved in type 1 neurofibromatosis; 4) sarcomas with MDM2/CDK4 amplification in the 12q13-15 amplicon, i.e. well differentiated or dedifferentiated liposarcomas; 5) sarcomas with complex genetics present more unrefined genetic changes (leiomyosarcomas, osteosarcomas). On top these 5 groups, desmoids tumors characterized by alterations of the Wnt, beta catenin, APC, and giant cell tumors of the bone, in which RANK/RANKL operates a complex interaction between the cellular stroma and giant tumor cells. The identification of these abnormal ways of road marking to licence the development of effective targeted therapeutic agents against certain rare histological connective subcategories of sarcomas and tumors with local aggressiveness, in particular DFSP, PVNS, GCST, PEComes, endometrial stromal sarcomas, Ewing sarcomas, etc. Imatinib is used in the treatment of DFSP, characterized by a translocation of the gene PDGF, or in pigmented villonodular synovitis (PVNS), a tumor of soft part also locally aggressive, caused by an abnormality of the gene coding for the M-CSF. Several clinical trials of phase I and II trials demonstrated the antitumor activity of anti-IGF1R antibodies in Ewing, whose fusion gene downregulates IGFBP3. Inhibitors of MDM2 are in the course of clinical evaluation in liposarcomas. Inhibitors of mTOR (sirolimus, temsirolimus) demonstrated an antitumoral activity in the PEComas. The molecular characterization of sarcomas allowed to develop therapeutic targeted to correct the responsible abnormalities. Translational research is and will be an essential tool for the development of new treatments and the identification of the mechanisms of answer and resistance set up by these tumors.

Neuroendocrine small cell carcinoma of the bladder is a rare and aggressive cancer with a very pejorative behavior. Neuroendocrine small cell carcinoma of bladder is a histological entity with special characteristics, rapidly aggressive and metastatic and with a poor prognosis. Because it is rare, there is no consensus to date. Its management should be multidisciplinary, involving surgery, chemotherapy and radiotherapy. We report the case of an 84-year-old patient with neuroendocrine small cell carcinoma of the bladder, treated by neoadjuvant chemotherapy followed by a combined chemoradiotherapy. A review of the literature on this topic is also presented.

Soft tissue sarcomas are rare tumors. They may occur in any part of the body. Early step of management are essential because they directly affect functional consequences and survival of patients. It is very important to rapidly evoke the diagnostic of soft tissue sarcoma. Multidisciplinary discussion is indispensable at different step of the management: before the diagnostic to organize radiological check up and preoperative biopsy, before resection of localized tumor to decide the surgical procedure, with anatomopathological results to discuss an adjuvant treatment, at metastatic setting to decide a systemic treatment to start or inclusion in a clinical trial.

High-performance liquid chromatography with internal surface reversed-phase packing provides an analytical tool for studying the in vitro and in vivo metabolism of A and E destruxins in the haemolymph and various organs of male adults of Locusta migratoria. A slight amount of injected E destruxin is shown to be hydrated into E-diol destruxin in the haemolymph. The rest of the toxin is recovered unchanged in the fat-body, pericardial tissues and Malpighian tubules, and some further E-diol destruxin formation occurs in these organs. Because E-diol destruxin is only weakly toxic, this appears to be a detoxication process.

The European bark beetle, Ips sexdentatus Boerner, carries fungi in puncture pits located on the proximal part of each mandible, the sides of the pronotum, and the elytra.On the pronotum, each mycangium corresponds to the cup-shaped depression surrounding each seta. Several type III gland cells are associated with each mycangium. The general organization of these cells, commonly found in the epidermis, corresponds to those described by other authors. Their finely granular secretions probably protect the fungi, assure spore adhesion, and also may temporarily inhibit their germination. Similar gland cells were scattered under unspecialized pronotal integument where fungi were not detected.Thus, it appears that this beetle has evolved a mechanism for the protection or dissemination, or both, of yeasts and fungi such as Ceratocystis sp. This relatively simple system seems to be as efficient as the more evolved mycangia of other species.

1. 1. The Koschewnikow glands (KG) of honeybee queens are composed of type III glandular units; secretions are emitted from ducts that open onto the entire surface of the intersegmental membrane. 2. 2. Secretory activity is characterized by the appearance of dense granules containing mainly glycoproteins, stained by periodic acid-thiocarbohydrazide-silver proteinate, extracted by pronase. In one-yearold mated queens, the gland degenerates. Secretory products originating from mitochondria are likely to be only carriers of pheromonal compounds. 3. 3. Topical treatment of worker bees (“pseudoqueens”) with EtOH extracts of queen Koschewnikow glands induced typical queen balling behaviour in workers of a bee colony. 4. 4. Twenty-eight compounds including acids, alcohols, alkanes and alkenes (C8H16C43H88) were characterized by gas liquid chromatography-mass spectrometry in queen KG extract. None of them is present in worker alarm pheromone which is secreted from worker KG.

Cuticle deposition and chitin synthesis in the wing pads of 1-day-old fifth-instar larvae of Locusta were stimulated in vitro by 20-hydroxyecdysone and makisterone A. Stimulation was dose-dependent from 2 × 10−7 to 2 × 10−5 M. The response appeared after a 36- to 48-h lag period characterized by inhibition of the postecdysial activity of the previous cuticular cycle. The hormones stimulated deposition of the epicuticular layers, triggered uptake of the chitin precursor N-acetyl-D-glucosamine and biosynthesis of chitin, and initiated microtubular bundle orientation. Ecdysone has no effect on these processes. Ecdysone and 20-hydroxyecdysone do not act synergistically on chitin biosynthesis. These data confirm earlier observations on the differential effects of the major forms of ecdysteroids, ecdysone and 20-hydroxyecdysone, on the activity of epidermal cells of locusts. Chitin biosynthesis by 20-hydroxyecdysone stimulated cells requires the integrity of the microtubular system and the chitin–synthetase complex. It was inhibited by colcemid, a microtubular poison, and by diflubenzuron, an inhibitor of chitin synthetase. These drugs had no effect on apolysis and epicuticular secretion. The in vitro biosynthesis of chitin was also inhibited by azadirachtin, a cytotoxic drug.

In the present study we have tried to: (1) correlate, according to the age and polyethism of worker bees, the ontogeny of their mandibular glands and the age-dependent changes of 2-heptanone levels and (2) evaluate the role of 2-heptanone in some social behavioural interactions of the honeybee. 1. (1) Each mandibular gland of the worker honeybee, Apis mellifera (Hymenoptera: Apidae), consists of an axial cavity lined with a thin cuticular intima elaborated by a flat epithelium, and of numerous glandular units (type 3), each with a duct cell and a large polyploid glandular cell. Mitochondria and endoplasmic reticulum are preponderant organelles. The Golgi apparatus is reduced; its activity is lysosomal. With increasing age, the size of the gland and the amount of 2-heptanone per headspace sample progressively increased. The increasing quantity of 2-heptanone from 0.1 μl at emergence to 7 μl in foraging bees, is strictly correlated with hypertrophy of the mitochondria, which are engaged in the production of heterogeneous bodies. 2. (2) Similar age-dependent changes of 2-heptanone levels were found in mandibular glands of workers from docile and aggressive colonies and the amount of 2-heptanone in foraging bees of the two groups was alike. Neither crushed glands nor 2-heptanone showed any direct effect as an alarm pheromone on guardian bees at hive entrances. 2-heptanone had either an attractive or a repulsive effect on guards, according to the season; it showed a repulsive effect when added to sucrose solution which was visited by foragers. 2-heptanone had a temporary, repulsive effect on the visitation of flowers by foraging bees, hence it seems to act as a “forage-marking” pheromone. 2-heptanone does not inhibit the germination of pollen grains.

Aim Anti-FZD10 antibody-DTPA-90Y (Anti-FZD10-DTPA-90Y) is a novel radioimmunotherapy treatment for synovial-sarcomas (SS) which associates a chimeric monoclonal antibody targeting FZD10 with 90 Yttrium radioisotope (90Y). The expression of FZD10 is observed in SS clinical samples with high frequency, while it is not detected in normal tissues except placenta. Based on pre-clinical data, Anti-FZD10-DTPA-90Y is expected to have potent anti-tumour activity in humans with SS, with little side effects. The objectives of this study were to determine tumour uptake and biodistribution of Anti-FZD10-DTPA, to evaluate the absorbed dose to critical organs and to support the treatment decision. Materials and method Ten patients with relapsed or refractory non resectable SS were enrolled. They received an injection of approximately 185 MBq of 111In-Anti-FZD10-DTPA for pretreatment dosimetric study. Two quantitative imaging protocols have been designed: 2D (based on whole-body gamma-cameras scan) and 3D (based on SPECT/CT). The scans were obtained at different time points: 1-h (without urination), 2 h, 5 h, 24 h, 48 h, 72 h and 144 h after 111In-Anti-FZD10-DTPA injection. The conjugate-view technique was applied to anterior and posterior images after background, scatter and attenuation corrections. The radiation absorbed dose of 90Y-Anti-FZD10-DTPA to heart, lungs, liver, spleen, kidneys, bladder and bone marrow has been evaluated by calculating the cumulated activity in each of these organs from region of interest drawn on planar and SPECT/CT 111In-Anti-FZD10-DTPA imaging. Based on these calculations, and mostly the dose to tumour, the decision to treat with 90Y-Anti-FZD10-DTPA was taken by the scientific committee. Results Scintigraphic images showed blood vessel activity in arteries and an early uptake in liver persisting over time. Median absorbed doses for 90-yttrium (mGy/MBq) were 3.5, 5.6, 3.8, 2.8, 0.5 to heart, liver, spleen, kidneys and bladder respectively. The uptake in lungs and bone marrow was negligible. No toxicity was observed. Conclusion 90Y-Anti-FZD10-DTPA seems to be a well tolerated therapy, with potential efficiency and high tumour specificity. An ancillary study aims to analyze the correlation between predictive dosimetry from 111In imaging and actual dose delivered by the treatment from SPECT/CT and PETC/CT imaging of Yttrium-90.

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The insect societies are stable structures submitted to various qualitative and quantitative regulations funded on the perception of mechanical, acoustic, visual and mainly chemical stimuli. The chemical informations provided by the biotic environment are named allomones if they trigger a defensive behaviour, kairomone if they allow an attractive one to the emitor. The pheromones secreted by conspecific individuals, belonging or not to the same group or society, act immediatly on the behaviour (primer) or after a lag time on the physiology (releaser) of the receptive insect. The blend or pheromonal bouquet is truly the identity card of each insect.

Both queen and worker honey bees secrete specific alarm pheromones which trigger different behavioural patterns in each female caste.

La secretion de la cire par les ouvrieres de l'abeille italienne (A m var ligustica) est le fait de complexes glandulaires, localises a la partie anterieure des sternites abdominaux IV a VII, recouverts par des zones cuticulaires amincies ou miroirs. Chaque complexe glandulaire comporte 3 types cellulaires (cellules epitheliales, œnocytes et adipocytes), dont l'activite synchrone est fonction de l'âge de l'abeille. La cire est un melange d'hydrocarbures, d'acides gras et de proteines. La structure des miroirs et des differents types cellulaires a ete etudiee a l'echelle de la microscopie electronique a balayage et a transmission afin de preciser les relations entre structures cuticulaires et cellulaires, et d'envisager le transit des constituants de la cire. Au niveau des miroirs (figs 1-4) la cuticule amincie (2-4 μm) est remarquable par le grand developpement du systeme fibrillaire (20 nm) des canaux poraires connectes d'une part aux canaux ciriers epicuticulaires et d'autre part aux fibrilles extracellulaires localisees dans des invaginations de la membrane plasmique apicale des cellules epitheliales. Les cellules epitheliales (figs 4-6) reunies par un systeme jonctionnel complexe (fig 7) (desmosome, desmosome cloisonne, jonction serree) possedent de longues citernes de reticulum endoplasmique agranulaire (fig 8) contenant le meme materiel que celui qui subsiste a la surface des miroirs a l'issue des traitements de la microscopie electronique. Les citernes semblent en relation avec les espaces extracellulaires (fig 8). Les œnocytes (fig 9) a l'origine des hydrocarbures de la cire possedent un abondant reticulum endoplasmique agranulaire, tubulaire et de nombreuses structures lytiques traduisant un intense metabolisme. Les adipocytes riches en reticulum granulaire, en lipides et en glycogene doivent couvrir les besoins energetiques des complexes glandulaires. Lipophorines hemolymphatiques, hydrocarbures synthetises par les œnocytes traversent les cellules epitheliales par l'intermediaire des citernes de reticulum agranulaire et la cuticule le long des structures fibrillaires (canaux poraires et canaux ciriers)