[Cancers of the external genital organs of male in Hérault: Results from the Hérault tumor register (RTH) over a period of 30 years (1987-2016)]. / Le cancer des organes génitaux externes de l'homme dans le département de l'Hérault: résultats de 30 ans d'enregistrement du registre des tumeurs de l'Hérault (1987­2016).

AIM: The objective of this study is to present the history of cancers of the external genital organs of male in Hérault using data from the Hérault tumor register (RTH) over a period of 30 years. PATIENTS AND METHODS: Using the RTH database, we studied the development of testicular germ cell tumors (TGCT) and penile cancer (PC) over 30 years, from 1987 to 2016. We analyzed the incidence and mortality data for these tumors. We compared these results to French, European and global data. RESULTS: In 30 years of registration we have recorded 725 cases of TGCT and 175 cases of PC. The age standardized incidence rate (ASR) of TGCT has doubled between 1987 and 2016 (4.2 per 100,000 in 1987 and 9.3 per 100,000 in 2016). It was multiplied by 2.63 in the population of patients aged 30 to 44. There is a decrease of the mortality rate with a ASR of 0.8 deaths per 100,000 in 1987, and 0.4/100 000 in 2016. The PC incidence ASR was stable between 1987 and 2016 (0.4-0.9/100,000). Mortality is stable with a ASR between 0.1 and 0.3 deaths per 100,000 between 1987 and 2016. CONCLUSION: The incidence of TGCT has increased sharply in the Hérault over the past 30 years, while a decrease in mortality has been observed. The proportion of seminomas is increasing; it has gone from 53 % to 60 % in 30 years in the Hérault. The incidence and mortality of PC shows a stability in the Hérault over the past 30 years.

[RHESOU (Registry in HErault Specialized in Onco-Urology) : the first French Registry specialized in Onco-Urology. One-year experience]. / RHESOU (Registre de l'Hérault spécialisé en onco-urologie) : le premier registre français spécialisé en onco-urologie. Un outil méthodologique de recueil de données en onco-urologie. Bilan de faisabilité sur un an d'expérience.

PURPOSE: In 2016, the Herault tumor registry collected 1961cancers in urology (21.4 % from all Herault cancers this year). RHESOU was created to complete RTH' data with specific parameters in onco-urology. The aim of this study is to describe RHESOU and to give some examples with our first results. MATERIAL AND METHODS: In November 2018, RHESOU (Registry HErault Specialised in Onco-Urology) was founded with the same registry recommendations. It collects specific oncologic parameters and also complete RTH's data. For each urological cancer, a specific survey with different choices was performed to collect a maximum of data which could be present in patients' file. These surveys were used for urological cancers cases that live in Herault in 2017. RESULTS: In 2017, we collected 970 prostate cancers, 581 bladder cancers, 212 kidney cancers, 51 upper excretory tract cancers, 28 testicle cancers and 9 penil cancers. Our urological data collection gives many possibilities to create many requests for detailed analysis in urological cancers. In this article, we reported data from kidney, bladder and prostate cancers. CONCLUSIONS: RHESOU is a new tool opened to the different urologic corporations (urologists, pathologists, oncologists, radiotherapists, radiologists) that permits an overview in urological cancers in Herault. Finally, one important aim is that this tool will be adapted when new treatments or new important parameters appear in the years ahead. LEVEL OF EVIDENCE: 3.

[Results of surgical revisions for ureteral complications after renal transplantation]. / Résultats des reprises chirurgicales pour complications urétérales après transplantation rénale.

OBJECTIVE: To analyze the results of surgical revision for ureteral complication (ureteric stenosis or urinary leakage) after renal transplantation over a period of 10 years. MATERIALS AND METHODS: We performed a retrospective study on 1313 consecutive kidney transplantations carried out in a University Hospital Center between 2005 and 2014. The data of the patients who developed a ureteral stenosis or a urinary leakage secondary to a renal transplantation were analyzed. Combined organ transplantations (kidney-liver and kidney-pancreas), as well as pediatric transplantations were excluded. RESULTS: Seventy-six patients (5.8%) had ureteric stenosis or urinary leakage after renal transplantation. Forty-six patients (3.5%) underwent surgical revision: 27 for ureteral stenosis, 19 for urinary leakage. Early success was achieved in 26 patients (56.5%), including 14 ureteric stenosis (51.9%) and 12 urinary leakage (63.2%) (P=0.45). After a complementary endoscopic or surgical treatment, the final success rate was increased to 73.1% (34 patients): 20 ureteric stenosis (74.1%) and 14 urinary leakage (73.7%) (P=0.98). There were 2 graft losses (4.3%) and one death (2.2%). The mean glomerular filtration rate estimated by the MDRD was 44.58mL/min/1.73m2 (±14.7) before surgery and 45.37mL/min/1.73m2 (±16.5) 6 months after surgery (P=0.92). CONCLUSION: Although frequently challenging, surgical revisions for ureteral complications after renal transplantation give good results, with a low rate of graft loss and mortality. LEVEL OF EVIDENCE: 4.

Overall survival and oncological outcomes after partial nephrectomy and radical nephrectomy for cT2a renal tumors: A collaborative international study from the French kidney cancer research network UroCCR.

BACKGROUND: Partial nephrectomy (PN) is recommended as first-line treatment for cT1 stage kidney tumors because of a better renal function and probably a better overall survival than radical nephrectomy (RN). For larger tumors, PN has a controversial position due to lack of evidence showing good cancer control. The aim of this study was to compare the results of PN and RN in cT2a stage on overall survival and oncological results. METHOD: A retrospective international multicenter study was conducted in the frame of the French kidney cancer research network (UroCCR). We considered all patients aged≥18 years who underwent surgical treatment for localized renal cell carcinoma (RCC) stage cT2a (7.1-10cm) between 2000 and 2014. Cox and Fine-Gray models were performed to analyze overall survival (OS), cancer specific survival (CSS) and cancer-free survival (CFS). Comparison between PN and RN was realized after an adjustment by propensity score considering predefined confounding factors: age, sex, tumor size, pT stage of the TNM classification, histological type, ISUP grade, ASA score. RESULTS: A total of 267 patients were included. OS at 3 and 5 years was 93.6% and 78.7% after PN and 88.0% and 76.2% after RN, respectively. CSS at 3 and 5 years was 95.4% and 80.2% after PN and 91.0% and 85.0% after RN. No significant difference between groups was found after propensity score adjustment for OS (HR 0.87, 95% CI: 0.37-2.05, P=0.75), CSS (HR 0.52, 95% CI: 0.18-1.54, P=0.24) and CFS (HR 1.02, 95% CI: 0.50-2.09, P=0.96). CONCLUSION: PN seems equivalent to RN for OS, CSS and CFS in cT2a stage kidney tumors. The risk of recurrence is probably more related to prognostic factors than the surgical technique. The decision to perform a PN should depend on technical feasibility rather than tumor size, both to imperative and elective situation. LEVEL OF EVIDENCE: 4.

Is it possible to improve the breaking bad news skills of residents when a relative is present? A randomised study.

BACKGROUND: Although patients with cancer are often accompanied by a relative during breaking bad news (BBN) consultations, little is known regarding the efficacy of training programmes designed to teach residents the communication skills needed to break bad news in a triadic consultation. METHODS: Residents were randomly assigned to a 40-h dyadic and triadic communication skills training programme (n=48) or a waiting list (n=47). A simulated BBN triadic consultation was audiotaped at baseline, and after training for the training group, and 8 months after baseline for the waiting list group. Transcripts were analysed using content analysis software (LaComm). A coder determined the moment of bad news delivery and the relative's first turn of speech regarding the bad news. A generalised estimating equation was used to evaluate residents' communication skills, BBN timing, and the relative's inclusion in the consultation. RESULTS: Ninety-five residents were included. After training, the duration of the pre-delivery phase was found to be longer for the trained residents (relative risk (RR)=3.04; P<0.001). The simulated relative's first turn of speech about the bad news came more often during the pre-delivery phase (RR=6.68; P=0.008), and was more often initiated by the trained residents (RR=19.17; P<0.001). Trained residents also used more assessment (RR=1.83; P<0.001) and supportive utterances (RR=1.58; P<0.001). CONCLUSION: This study demonstrates that a training programme that focuses on the practice of dyadic and triadic communication skills can improve the communication skills of the participating residents in a BBN triadic consultation. Such a training should be included in resident curriculum.

Is it possible to improve residents breaking bad news skills? A randomised study assessing the efficacy of a communication skills training program.

BACKGROUND: This study aims to assess the efficacy of a 40-h training programme designed to teach residents the communication skills needed to break the bad news. METHODS: Residents were randomly assigned to the training programme or to a waiting list. A simulated patient breaking bad news (BBN) consultation was audiotaped at baseline and after training in the training group and 8 months after baseline in the waiting-list group. Transcripts were analysed by tagging the used communication skills with a content analysis software (LaComm) and by tagging the phases of bad news delivery: pre-delivery, delivery and post-delivery. Training effects were tested with generalised estimating equation (GEE) and multivariate analysis of variance (MANOVA). RESULTS: The trained residents (n=50) used effective communication skills more often than the untrained residents (n=48): more open questions (relative rate (RR)=5.79; P<0.001), open directive questions (RR=1.71; P=0.003) and empathy (RR=4.50; P=0.017) and less information transmission (RR=0.72; P=0.001). The pre-delivery phase was longer for the trained (1 min 53 s at baseline and 3 min 55 s after training) compared with the untrained residents (2 min 7 s at baseline and 1 min 46 s at second assessment time; P<0.001). CONCLUSION: This study shows the efficacy of training programme designed to improve residents' BBN skills. The way residents break bad news may thus be improved.

The prognostic benefit of tumour-infiltrating Natural Killer cells in endometrial cancer is dependent on concurrent overexpression of Human Leucocyte Antigen-E in the tumour microenvironment.

BACKGROUND: Human Leucocyte Antigen- E (HLA-E) has been reported as both a positive and negative prognostic marker in cancer. This apparent discrepancy may be due to opposing actions of HLA-E on tumour-infiltrating immune cells. Therefore, we evaluated HLA-E expression and survival in relation to the presence of intratumoural natural killer (NK) cells and cytotoxic T cells (CTLs). METHODS: Tissue microarrays (TMAs) of endometrial tumours were used for immunohistochemical staining of parameters of interest. The combined impact of clinical, pathological and immune parameters on survival was analysed using log rank testing and Cox regression analyses. RESULTS: Upregulation of HLA-E was associated with an improved disease-free and disease-specific survival in univariate analysis (HR 0.58 95% CI 0.37-0.89; HR 0.42 95% CI 0.25-0.73, respectively). In multivariate analysis, the presence of NK cells predicts survival with a hazard ratio (HR) 0.28 (95% confidence interval (CI) 0.09-0.91) when HLA-E expression is upregulated; but it is associated with a worse prognosis when HLA-E expression is normal (HR 13.43, 95% CI 1.70-106.14). By contrast, the prognostic benefit of T cells was not modulated by HLA-E expression. CONCLUSIONS: Taken together, we demonstrate that the prognostic benefit of NK cells, but not T-cells, is influenced by HLA-E expression in endometrial cancer (EC) and propose a model to explain our observations.

Influence of dissolved gases on sonochemistry and sonoluminescence in a flow reactor.

In the present work, the influence of gas addition is investigated on both sonoluminescence (SL) and radical formation at 47 and 248 kHz. The frequencies chosen in this study generate two distinct bubble types, allowing to generalize the conclusions for other ultrasonic reactors. In this case, 47 kHz provides transient bubbles, while stable ones dominate at 248 kHz. For both bubble types, the hydroxyl radical and SL yield under gas addition followed the sequence: Ar>Air>N2>>CO2. A comprehensive interpretation is given for these results, based on a combination of thermal gas properties, chemical reactions occurring within the cavitation bubble, and the amount of bubbles. Furthermore, in the cases where argon, air and nitrogen were bubbled, a reasonable correlation existed between the OH-radical yield and the SL signal, being most pronounced under stable cavitation at 248 kHz. Presuming that SL and OH originate from different bubble populations, the results indicate that both populations respond similarly to a change in acoustic power and dissolved gas. Consequently, in the presence of non-volatile pollutants that do not quench SL, sonoluminescence can be used as an online tool to qualitatively monitor radical formation.

Molecular basis of the cell-specific activity of v-erb A in quail myoblasts.

We have previously shown that v-erb A expression strongly stimulates quail myoblast proliferation and differentiation without alteration of the triiodothyronine (T3) influence in this cell type. In order to understand the molecular basis of v-erb A action in myoblasts, we have studied the influence of this oncoprotein on c-erb A alpha1 encoded T3 nuclear receptor (TR alpha) activity. In transfection experiments, v-erb A did not inhibit the T3-dependent c-erb A alpha1 transcriptional activity in QM7 myoblasts in contrast to its action in HeLa cells. However, it repressed the retinoic acid receptor RAR alpha activity in both cell-types, indicating that v-erb A interactions with T3 or RA mediated transcription significantly differs. In EMSA experiments using a TREpa1 probe, T3R alpha binds as three complexes in HeLa cells. We have previously identified the slow migrating complex, undetectable in QM7 myoblasts, as a T3R/RXR heterodimer. Interestingly, v-erb A inhibited binding of this complex in HeLa cells, but did not affect binding of the two other complexes in QM7 myoblasts. Expression of RXR (gamma isoform), the TR alpha dimerization partner absent in proliferating QM7 cells, restored inhibition of c-erb A alpha1 transcriptional activity in these cells and abrogated the v-erb A myogenic influence. Lastly, v-erb A induced a T3-independent c-erb A alpha1 activity in QM7 cells when cotransfected in equimolar ratio with the receptor, by inhibiting AP-1 activity and stimulating transcription of a reporter gene driven by a TRE sequence.

v-erbA stimulates quail myoblast differentiation in a T3 independent, cell-specific manner.

The v-erbA oncoprotein represents a mutated version of a thyroid hormone receptor, responsible for the induction of a differentiation arrest in chicken erythroid cells. We have studied the influence of v-erbA on proliferation and differentiation of avian myoblasts. Secondary quail myoblast cultures were infected either with an avian retrovirus carrying the v-erbA oncogene in association with the neomycin resistance gene, or with a control deleted v-erbA/neoR alpha retrovirus. We report here that v-erbA expression led to an increase in myoblast proliferation and to a surprising stimulation of quail myoblast terminal differentiation. In addition, these effects occurred in the presence or absence of T3, and v-erbA did not suppress T3 influence on myoblasts. Transient transfection assays demonstrated that, in contrast to its action in HeLa cells, v-erbA was unable to repress the transcriptional activation of a TRE-CAT reporter gene by liganded c-erbA alpha receptors in quail myoblasts. We also observed that the AP-1/c-erbA/v-erbA interactions are not functional in quail myoblasts. These data suggest that, in these cells, v-erbA action does not interfere with T3 induced mechanisms. They also demonstrate a cell specificity for the v-erbA pathway. Lastly, expression of c-erbA/v-erbA chimeric proteins and of the S61G v-erbA mutant indicates that the DNA binding domain of v-erbA, and more specifically serine 61, is directly involved in the enhancement of myoblast differentiation by the oncoprotein.

Structural and biochemical investigations of the catalytic mechanism of an NADP-dependent aldehyde dehydrogenase from Streptococcus mutans.

The NADP-dependent non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans (abbreviated Sm-ALDH) belongs to the aldehyde dehydrogenase (ALDH) family. Its catalytic mechanism proceeds via two steps, acylation and deacylation. Its high catalytic efficiency at neutral pH implies prerequisites relative to the chemical mechanism. First, the catalytic Cys284 should be accessible and in a thiolate form at physiological pH to attack efficiently the aldehydic group of the glyceraldehyde-3-phosphate (G3P). Second, the hydride transfer from the hemithioacetal intermediate toward the nicotinamide ring of NADP should be efficient. Third, the nucleophilic character of the water molecule involved in the deacylation should be strongly increased. Moreover, the different complexes formed during the catalytic process should be stabilised. The crystal structures presented here (an apoenzyme named Apo2 with two sulphate ions bound to the catalytic site, the C284S mutant holoenzyme and the ternary complex composed of the C284S holoenzyme and G3P) together with biochemical results and previously published apo and holo crystal structures (named Apo1 and Holo1, respectively) contribute to the understanding of the ALDH catalytic mechanism. Comparison of Apo1 and Holo1 crystal structures shows a Cys284 side-chain rotation of 110 degrees, upon cofactor binding, which is probably responsible for its pK(a) decrease. In the Apo2 structure, an oxygen atom of a sulphate anion interacts by hydrogen bonds with the NH2 group of a conserved asparagine residue (Asn154 in Sm-ALDH) and the Cys284 NH group. In the ternary complex, the oxygen atom of the aldehydic carbonyl group of the substrate interacts with the Ser284 NH group and the Asn154 NH2 group. A substrate isotope effect on acylation is observed for both the wild-type and the N154A and N154T mutants. The rate of the acylation step strongly decreases for the mutants and becomes limiting. All these results suggest the involvement of Asn154 in an oxyanion hole in order to stabilise the tetrahedral intermediate and likely the other intermediates of the reaction. In the ternary complex, the cofactor conformation is shifted in comparison with its conformation in the C284S holoenzyme structure, likely resulting from its peculiar binding mode to the Rossmann fold (i.e. non-perpendicular to the plane of the beta-sheet). This change is likely favoured by a characteristic loop of the Rossmann fold, longer in ALDHs than in other dehydrogenases, whose orientation could be constrained by a conserved proline residue. In the ternary and C284S holenzyme structures, as well as in the Apo2 structure, the Glu250 side-chain is situated less than 4 A from Cys284 or Ser284 instead of 7 A in the crystal structure of the wild-type holoenzyme. It is now positioned in a hydrophobic environment. This supports the pK(a) assignment of 7.6 to Glu250 as recently proposed from enzymatic studies.

Characterization of the pressure-induced intermediate and unfolded state of red-shifted green fluorescent protein--a static and kinetic FTIR, UV/VIS and fluorescence spectroscopy study.

The green fluorescence proteins (GFP) are widely used as reporters in molecular and cell biology. For their use it in high-pressure microbiology and biotechnology studies, their structural properties, thermodynamic parameters and stability diagrams have to be known. We investigated the pressure stability of the red-shifted green fluorescent protein (rsGFP) using Fourier-transform infrared spectroscopy, fluorescence and UV/Vis spectroscopy. We found that rsGFP does not unfold up to approximately 9kbar at room temperature. Its unique three-dimensional structure is held responsible for the high-pressure stability. At higher temperatures, its secondary structure collapses below 9kbar (e.g. the denaturation pressure at 58 degrees C is 7.8kbar). The analysis of the IR data shows that the pressure-denatured state contains more disordered structures at the expense of a decrease of intramolecular beta-sheets. As indicated by the large volume change of DeltaV degrees (u) approximately -250(+/-50)mlmol(-1) at 58 degrees C, this highly cooperative transition can be interpreted as a collapse of the beta-can structure of rsGFP. For comparison, the temperature-induced unfolding of rsGFP has also been studied. At high temperature (T(m)=78 degrees C), the unfolding resulted in the formation of an aggregated state. Contrary to the pressure-induced unfolding, the temperature-induced unfolding and aggregation of GFP is irreversible. From the FT-IR data, a tentative p,T-stability diagram for the secondary structure collapse of GFP has been obtained. Furthermore, changes in fluorescence and absorptivity were found which are not correlated to the secondary structural changes. The fluorescence and UV/Vis data indicate smaller conformational changes in the chromophore region at much lower pressures ( approximately 4kbar) which are probably accompanied by the penetration of water into the beta-can structure. In order to investigate also the kinetics of this initial step, pressure-jump relaxation experiments were carried out. The partial activation volumes observed indicate that the conformational changes in the chromophore region when passing the transition state are indeed rather small, thus leading to a comparably small volume change of -20 ml mol(-1) only. The use of the chromophore absorption and fluorescence band of rsGFP in using GFP as reporter for gene expression and other microbiological studies under high pressure conditions is thus limited to pressures of about 4kbar, which still exceeds the pressure range relevant for studies in vivo in micro-organisms, including piezophilic bacteria from deep-sea environments.

Apo and holo crystal structures of an NADP-dependent aldehyde dehydrogenase from Streptococcus mutans.

The aldehyde dehydrogenases (ALDHs) are a superfamily of multimeric enzymes which catalyse the oxidation of a broad range of aldehydes into their corresponding carboxylic acids with the reduction of their cofactor, NAD or NADP, into NADH or NADPH. At present, the only known structures concern NAD-dependent ALDHs. Three structures are available in the Protein Data Bank: two are tetrameric and the other is a dimer. We solved by molecular replacement the first structure of an NADP-dependent ALDH isolated from Streptococcus mutans, in its apo form and holo form in complex with NADP, at 1.8 and 2.6 A resolution, respectively. Although the protein sequence shares only approximately 30 % identity with the other solved tetrameric ALDHs, the structures are very similar. However, a large local conformational change in the region surrounding the 2' phosphate group of the adenosine moiety is observed when the enzyme binds NADP, in contrast to the NAD-dependent ALDHs. Structure and sequence analyses reveal several properties. A small number of residues seem to determine the oligomeric state. Likewise, the nature (charge and volume) of the residue at position 180 (Thr in ALDH from S. mutans) determines the cofactor specificity in comparison with the structures of NAD-dependent ALDHs. The presence of a hydrogen bond network around the cofactor not only allows it to bind to the enzyme but also directs the side-chains in a correct orientation for the catalytic reaction to take place. Moreover, a specific part of this network appears to be important in substrate binding. Since the enzyme oxidises the same substrate, glyceraldehyde-3-phosphate (G3P), as NAD-dependent phosphorylating glyceraldehyde-3-phosphate dehydrogenases (GAPDH), the active site of GAPDH was compared with that of the S. mutans ALDH. It was found that Arg103, Arg283 and Asp440 might be key residues for substrate binding.

The powerful high pressure tool for protein conformational studies.

The pressure behavior of proteins may be summarized as a the pressure-induced disordering of their structures. This thermodynamic parameter has effects on proteins that are similar but not identical to those induced by temperature, the other thermodynamic parameter. Of particular importance are the intermolecular interactions that follow partial protein unfolding and that give rise to the formation of fibrils. Because some proteins do not form fibrils under pressure, these observations can be related to the shape of the stability diagram. Weak interactions which are differently affected by hydrostatic pressure or temperature play a determinant role in protein stability. Pressure acts on the 2 degrees, 3 degrees and 4 degrees structures of proteins which are maintained by electrostatic and hydrophobic interactions and by hydrogen bonds. We present some typical examples of how pressure affects the tertiary structure of proteins (the case of prion proteins), induces unfolding (ataxin), is a convenient tool to study enzyme dissociation (enolase), and provides arguments to understand the role of the partial volume of an enzyme (butyrylcholinesterase). This approach may have important implications for the understanding of the basic mechanism of protein diseases and for the development of preventive and therapeutic measures.

Antiproliferative activity of thermosensitive liposome-encapsulated doxorubicin combined with 43 degrees C hyperthermia in sensitive and multidrug-resistant MCF-7 cells.

Thermosensitive liposome-encapsulated doxorubicin (TLED) was compared to free doxorubicin, at 37 degrees C or combined with 43 degrees C hyperthermia, in sensitive and multidrug-resistant MCF-7 human tumour cells using clonogenic assays. In the resistant subline, TLED was found to partly circumvent multidrug resistance (MDR). The reversal was comparable to that obtained when verapamil was added to free doxorubicin. When hyperthermic treatment was applied, no difference in thermosensitivity was found between sensitive and resistant cells. The combination of hyperthermia with free doxorubicin did not reverse MDR. Hyperthermia and TLED yielded additive effects in the resistant cells while potentiation was observed in the sensitive cells. These results confirmed the usefulness of the liposome encapsulation of doxorubicin in reversing MDR. The possibility of obtaining additive cytotoxicity using TLED combined with hyperthermia may represent an alternative way of intensification of doxorubicin cytotoxicity concomitant with the circumvention of MDR without using MDR reversing agents, which often generate limiting toxic side-effects.

The effects of a 24-h psychological training program on attitudes, communication skills and occupational stress in oncology: a randomised study.

The usefulness of psychological training programs (P.T.P.) in health care settings devoted to cancer care is beginning to be recognised but their content, form and effectiveness need further investigation. Seventy-two oncology nurses were randomly assigned to a 24-h P.T.P. or to a waiting list period. Attitudes were assessed by a semantic differential questionnaire, occupational stress was assessed by the Nursing Stress Scale and communication skills were assessed by standardised videotaped role-playing exercises. These were used to compare trained (T.S.) and control subjects (C.S.). The results show a significant training effect on attitudes (P = 0.05), especially on those related to self concept (P = 0.004), and on the level of occupational stress related to inadequate preparation (P = 0.02). Limited changes were found regarding post-training communication skills. T.S. were significantly more in control of the interview than C.S. (P = 0.02). The results indicate that 24-h P.T.P. assessed here are effective. The data also demonstrate the need to consolidate the skills acquired by regular post-training sessions.

Radiosensitivity of multicellular tumour spheroids obtained from human ovarian cancers.

The radioresponsiveness of immunologically characterised (KL1, antivimentin and OC125) human ovarian carcinoma cells, obtained from effusions or solid tumours, was assayed in vitro using the multicellular tumour spheroids (MTS) three-dimensional model. Great interspecimen variabilities were observed in MTS doubling time (1.0-8.5 days), as well as in the doses inducing a 50% decrease in the MTS individual volume (ID50) (0.56-9.15 Gy), or in the overall population MTS number (SCD50) (1.9-15.7 Gy) and the residual/initial MTS individual volume ratio after 2 Gy irradiation (RSV2) (10-88%). The doubling time, DNA-ploidy and S-phase fraction did not correlate with the ID50. Significant correlations were found between the new parameters defined (RSV2 and ID50) and the SCD50, a well-accepted local control parameter. These parameters demonstrated their usefulness for studying the radiosensitivity of MTS prepared from human ovarian tumour biopsies.

v-erb A and v-erb B do not cooperate in quail myoblasts.

We have previously shown that v-erb A stimulates quail myoblast differentiation in a T3 independent, cell-specific manner. In this work, we have studied the influence of v-erb B (the second oncogene carried in the AEV genome) upon quail myoblast proliferation and differentiation. v-erb B expression,moderately stimulates myoblast proliferation, and inhibits differentiation. Moreover, this oncoprotein fully inhibits the v-erb A myogenic influence. These data provide evidence that these two oncogenes do not cooperate in avian myoblasts. Consequently, in contrast to results obtained in other cell-types, coexpression of both oncogenes does not transform quail myoblasts.

Involvement of neutrophilic granulocytes in the uptake of biodegradable non-stealth and stealth nanoparticles in guinea pig.

The in vivo behavior of monomethoxypoly(ethylene oxide)-poly(lactic acid) (MPEO20-PLA45/PLA (75/25)) nanoparticles in comparison with PLA ones was studied in guinea pig. Indeed, the aim of this study was to bring to the fore the in vivo stealth character of these copolymer nanoparticles and to identify the phagocytic circulating cells involved in their uptake. After the intravascular administration of fluorescent nanoparticles (rubrene), their phagocytosis by granulocytes and monocytes was assayed by flow cytometry. At the same time, the evolution of the number of these phagocytic cells was realized in order to identify their function in the nanoparticle uptake. Finally, a histological study of the spleen (30 h after the nanoparticle administration) was investigated to highlight the splenic trapping of these stealth nanoparticles. This study has shown that the phagocytic circulating cells involved in the nanoparticle uptake were mainly neutrophilic granulocytes and some of them were found in the spleen.