Cancer de la prostate résistant à la castration (CRPC). Revue de la littérature en 2016

Introduction : Le cancer de la prostate en Tunisie est la troisième cause de mortalité par cancer après le cancer du poumon et les cancers colorectaux. L'avènement récent des hormonothérapies de nouvelle génération a révolutionné la prise en charge du cancer de la prostate résistant à la castration (CPRC). Plusieurs options thérapeutiques sont désormais disponibles en pré et en post Docetaxel. L’objectif de notre travail était d’étudier les différentes stratégies thérapeutiques dans le CPRC. Méthodes : Nous avons effectué une recherche bibliographique sur Pubmed, Medline, Cochrane   et en se référant aux recommandations internationales des sociétés savantes : AFU, EAU, ESMO, NCCN concernant les protocoles thérapeutiques des CPRC. Résultats : De nombreuses nouvelles classes thérapeutiques sont à différents stades de leur développement pour le CPRC. La connaissance de la biologie tumorale a mis en évidence l’implication de nouvelles cibles thérapeutiques comme le récepteur aux androgènes. Selon cette revue de la littérature, des immunothérapies, de nouvelles hormonothérapies, de nouveaux anti-androgènes, des thérapies ciblées et de nouveaux traitements ciblant l’os métastatique ont enrichis-la prise en charge thérapeutique des CPRC. Conclusion : Les progrès dans la prise en charge médicale du patient atteint de CPRC sont en nette progression et ce depuis 2004. L’année 2010 a été particulièrement riche en nouvelles thérapies, avec notamment les hormonothérapies de deuxième génération utilisées en pré et post Docetaxel. Tout le challenge actuel est de proposer la séquence thérapeutique optimale pour chaque patient, d’où le concept de médecine personnalisée.

Tumeur neuro-ectodermique primitive du rein avec insuffisance rénale

Introduction : Les Tumeurs neuroectodermiques périphériques (PNET) ou le sarcome d'Ewing est un cancer qui se développe habituellement dans les os et la localisation extrasquelettique est rare. Les PNET de localisation rénale sont rares et se caractérisent par une évolution clinique agressive et un mauvais pronostic. Seuls quelques cas de PNET rénaux avec insuffisance rénale ont été rapportés dans la littérature à ce jour.  Cas clinique : Nous présentons un cas de PNET rénal chez un homme de 48 ans sans antécédents médicaux, qui présentait une douleur au flanc droit, imitant des coliques nephretiques. Une échographie abdominale a montré une masse rénale droite.  La tomodensitométrie a montré une masse du rein droit de 23x9 cm associée à une carcinose péritonéale, la tumeur été localement avancé avec invasion vasculaire et des structures adjacentes. L'analyse histologique a trouvé de petites cellules rondes monomorphes qui forment des rosettes. à l’immunohistochimie, les cellules tumorales sont fortement positifs pour le CD99 et la vimentine confirmant le diagnostic de PNET. Le patient a développé une insuffisance rénale au début de l'évolution de la maladie qui nous a empêchés de réaliser le bilan d’extension de la maladie et de prescrire une chimiothérapie. Le patient est décédé de sa maladie trois mois plus tard.Discussion : Les Tumeur neuroectodermique périphérique (PNET) de localisation rénale surviennent généralement pendant l'enfance, l'adolescence ou chez le jeune adulte ce qui n’est pas le cas de notre patient (48 ans). L’insuffisance rénale en association avec les PNET rénaux a été rapportée précédemment dans seulement quelques cas pédiatriques, mais pas dans la population adulte. cette insuffisance rénale peut être expliquer par: d'une part le thrombus direct qui envahit la veine rénale (20 à 30% des cas en pédiatrie), d'autre part l'étendue de la tumeur elle-même dans le rein et enfin la compression  par les adénopathies régionales. La présence d'une fonction rénale altérée complique encore la gestion de ces patients à risque élevé avant le traitement et également après le début de la chimiothérapie. Et ceci est un obstacle à l'utilisation d’une chimiothérapie potentiellement néphrotoxiques et de produit de contraste pour l'imagerie. Devrions-nous utiliser l'échographie, la tomodensitométrie sans produit de contraste ou l’imagerie par résonance magnétique pour la stadification et le suivi ? D'autres recherches peuvent répondre à ces questions.Conclusion : Les PNET de localisation rénale doivent être envisagées dans les tumeurs rénales de tous âges, mais plus particulièrement chez les enfants et les jeunes adultes. Cette tumeur a de nombreuses similitudes avec d'autres tumeurs rénales, il est important de diagnostiquer cette entité tôt avant l’apparition des complications et principalement l’insuffisance rénale

Diatoms biotechnology: various industrial applications for a greener tomorrow

The benefits of the complex microscopic and industrially important group of microalgae such as diatoms is not hidden and have lately surprised the scientific community with their industrial potential. The ability to survive in harsh conditions and the presence of different pore structures and defined cell walls have made diatoms ideal cell machinery to produce a variety of industrial products. The prospect of using a diatom cell for industrial application has increased significantly in synch with the advances in microscopy, metabarcoding, analytical and genetic tools. Furthermore, it is well noted that the approach of industry and academia to the use of genetic tools has changed significantly, resulting in a well-defined characterization of various molecular components of diatoms. It is possible to conduct the primary culturing, harvesting, and further downstream processing of diatom culture in a cost-effective manner. Diatoms hold all the qualities to become the alternative raw material for pharmaceutical, nanotechnology, and energy sources leading to a sustainable economy. In this review, an attempt has been made to gather important progress in the different industrial applications of diatoms such as biotechnology, biomedical, nanotechnology, and environmental technologies

Awareness of vitamin D deficiency among at-risk patients

<p>Abstract</p> <p>Background</p> <p>Vitamin D deficiency is a significant problem for a growing proportion of the UK population. Individuals with dark or covered skin are at particularly high risk due to ethno-cultural, environmental and genetic factors. We assessed the level of awareness of vitamin D deficiency among at-risk patients in order to identify groups most in need of education.</p> <p>Findings</p> <p>A cross-sectional survey using a piloted questionnaire was conducted among consecutive at-risk patients without a diagnosis of Vitamin D deficiency arriving at a large inner city general practice in the North West of England over a five day period. The survey was completed by 221 patients. The mean age was 35 years. 28% of them (n = 61) had never heard about vitamin D. Older patients (p = 0.003) were less likely to have heard about vitamin D. 54% of participants were unaware of the commonest symptoms of vitamin D deficiency. 34% did not expose their skin other than their face in the last one year, and 11% did not include vitamin D rich foods in their diet.</p> <p>Conclusion</p> <p>The majority of at-risk patients are aware of vitamin D; nevertheless, there is a significant lack of knowledge among older people, who have higher morbidity. A programme of targeted education of the at-risk population is recommended.</p

Gain of chromosome arm 17q is associated with unfavourable prognosis in neuroblastoma, but does not involve mutations in the somatostatin receptor 2 (SSTR2) gene at 17q24

Deletion of chromosome arm 1p and amplification of the MYCN oncogene are well-recognized genetic alterations in neuroblastoma cells. Recently, another alteration has been reported; gain of the distal part of chromosome arm 17q. In this study 48 neuroblastoma tumours were successfully analysed for 17q status in relation to known genetic alterations. Chromosome 17 status was detected by fluorescence in situ hybridization (FISH). Thirty-one of the 48 neuroblastomas (65%) showed 17q gain, and this was significantly associated with poor prognosis. As previously reported, 17q gain was significantly associated with metastatic stage 4 neuroblastoma and more frequently detected than both deletion of chromosome arm 1p and MYCN amplification in tumours of all stages. 17q gain also showed a strong correlation to survival probability (P = 0.0009). However, the most significant correlation between 17q gain and survival probability was observed in children with low-stage tumours (stage 1, 2, 3 and 4S), with a survival probability of 100% at 5 years from diagnosis for children with tumours showing no 17q gain compared to 52.5% for those showing 17q gain (P = 0.0021). This suggests that 17q gain as a prognostic factor plays a more crucial role in low-stage tumours. Expression of the somatostatin receptor 2 (SSTR2), localized in chromosome region 17q24, has in previous studies been shown to be positively related to survival in neuroblastoma. A point mutation in the SSTR2 gene has earlier been reported in a human small-cell lung cancer. In this study, mutation screening of the SSTR2 gene in 43 neuroblastoma tumours was carried out with polymerase chain reaction-based single-stranded conformation polymorphism/heteroduplex (SSCP/HD) and DNA sequencing, and none of the tumours showed any aberrations in the SSTR2 gene. These data suggest that mutations in the SSTR2 gene are uncommon in neuroblastoma tumours and do not correlate with either the 17q gain often seen or the reason some tumours do not express SSTR2 receptors. Overall, this study indicates that gain of chromosome arm 17q is the most frequently occurring genetic alteration, and that it is associated with established prognostic factors. © 1999 Cancer Research Campaig

The impact of clothing style on bone mineral density among post menopausal women in Morocco: a case-control study

BACKGROUND: The clothing style is an important factor that influences vitamin D production and thus bone mineral density. We performed a case-control study in order to evaluate the effect of veil wearing (concealing clothing) on bone mineral density in Moroccan post menopausal women. METHODS: The cases were osteoporotic women whose disease was assessed by bone mineral density measurement. Each patient was matched with a non osteoporotic woman for age, and body mass index. All our patients were without secondary causes or medications that might affect bone density. The veil was defined as a concealing clothing which covered most of the body including the arms, the legs and the head. This definition is this of the usual Moroccan traditional clothing style. RESULTS: 178 post menopausal osteoporotic patients and 178 controls were studied. The mean age of the cases and the controls was 63.2 years (SD 7) and the mean body mass index was 32.1 (SD 8). The results of crude Odds Ratios analyses indicated that wearing a veil was associated with a high risk of osteoporosis: OR 2.29 (95% CI, 1.38–3.82). Multiparity or a history of familial peripheral osteoporotic fractures had also a significant effect on increasing the osteoporosis risk (ORs: 1.87 (95% CI, 1.05–3.49) and 2.01 (95% CI, 1.20–3.38)). After a multiple regression analysis, wearing the veil and a history of familial osteoporotic fractures remained the both independent factors that increased the osteoporosis risk (ORs: 2.20 (95% CI, 1.22–3.9) and 2.19 (95% CI, 1.12–4.29) respectively). CONCLUSION: our study suggested that in Moroccan post menopausal women, wearing a traditional concealing clothing covering arms, legs and head increased the risk of osteoporosis. Further studies are required to evaluate the clinical impact of the above findings and to clarify the status of vitamin D among veiled women in Morocco

Suppression of LPS-induced inflammatory responses in macrophages infected with Leishmania

<p>Abstract</p> <p>Background</p> <p>Chronic inflammation activated by macrophage innate pathogen recognition receptors such as TLR4 can lead to a range of inflammatory diseases, including atherosclerosis, Crohn's disease, arthritis and cancer. Unlike many microbes, the kinetoplastid protozoan pathogen <it>Leishmania </it>has been shown to avoid and even actively suppress host inflammatory cytokine responses, such as LPS-induced IL-12 production. The nature and scope of <it>Leishmania</it>-mediated inflammatory cytokine suppression, however, is not well characterized. Advancing our knowledge of such microbe-mediated cytokine suppression may provide new avenues for therapeutic intervention in inflammatory disease.</p> <p>Methods</p> <p>We explored the kinetics of a range of cytokine and chemokine responses in primary murine macrophages stimulated with LPS in the presence versus absence of two clinically distinct species of <it>Leishmania </it>using sensitive multiplex cytokine analyses. To confirm that these effects were parasite-specific, we compared the effects of <it>Leishmania </it>uptake on LPS-induced cytokine expression with uptake of inert latex beads.</p> <p>Results</p> <p>Whilst <it>Leishmania </it>uptake alone did not induce significant levels of any cytokine analysed in this study, <it>Leishmania </it>uptake in the presence of LPS caused parasite-specific suppression of certain LPS-induced pro-inflammatory cytokines, including IL-12, IL-17 and IL-6. Interestingly, <it>L. amazonensis </it>was generally more suppressive than <it>L. major</it>. We also found that other LPS-induced proinflammatory cytokines, such as IL-1α, TNF-α and the chemokines MIP-1α and MCP-1 and also the anti-inflammatory cytokine IL-10, were augmented during <it>Leishmania </it>uptake, in a parasite-specific manner.</p> <p>Conclusions</p> <p>During uptake by macrophages, <it>Leishmania </it>evades the activation of a broad range of cytokines and chemokines. Further, in the presence of a strong inflammatory stimulus, <it>Leishmania </it>suppresses certain proinflammatory cytokine responses in a parasite-specific manner, however it augments the production of other proinflammatory cytokines. Our findings highlight the complexity of inflammatory cytokine signalling regulation in the context of the macrophage and <it>Leishmania </it>interaction and confirm the utility of the <it>Leishmania</it>/macrophage infection model as an experimental system for further studies of inflammatory regulation. Such studies may advance the development of therapies against inflammatory disease.</p

Youth as Actors of Change? The Cases of Morocco and Tunisia

In the last decades, ‘youth’ has increasingly become a fashionable category in academic and development literature and a key development (or security) priority. However, beyond its biological attributes, youth is a socially constructed category and also one that tends to be featured in times of drastic social change. As the history of the category shows in both Morocco and Tunisia, youth can represent the wished-for model of future citizenry and a symbol of renovation, or its ‘not-yet-adult’ status which still requires guidance and protection can be used as a justification for increased social control and repression of broader social mobilisation. Furthermore, when used as a homogeneous and undifferentiated category, the reference to youth can divert attention away from other social divides such as class in highly unequal societies