Diagnostic des phéochromocytomes et paragangliomes *<br/>Diagnosis of Pheochromocytomas and Paragangliomas

Pheochromocytoma and paraganglioma are tumors leading to increased morbidity and mortality. Over the last 20 years, several major advances allowed a better characterization of these tumors, either from an imaging or from a genetic viewpoint. This is especially the case for the hereditary characteristics of these tumors, as roughly 20 new genes have been identified. This is why the initial steps of the management of a pheochromocytoma and/or a paraganglioma now require a dedicated tertiary referral center. The aim of this review is to depict the diagnostic steps of these tumors, so as to allow the clinician to determine the optimal therapeutic strategy.

Résumé
Les phéochromocytomes et les paragangliomes sont des tumeurs rares responsables d’une surmorbidité et d’une surmortalité. Au cours de ces 20 dernières années, de nombreuses avancées ont permis de mieux les caractériser sur le plan phénotypique (via l’imagerie métabolique) et génotypique (avec la mise en évidence de nombreux gènes de pré- disposition). La prise en charge d’un phéochromocytome ou d’un paragangliome nécessite désormais le recours à un centre expert dès la phase diagnostique. L’objectif de cette revue est de souligner les principales caractéristiques de ces tumeurs, et ce, afin de sensibiliser le clinicien aux différentes étapes permettant d’aboutir à une prise en charge optimale.     

An annexin 1 (ANXA1)-derived peptide inhibits prototype antigen-driven human T cell Th1 and Th2 responses in vitro

BACKGROUND: Annexin-1 (ANXA1, lipocortin 1) is a pleiotrophic protein produced by many cell types including peripheral blood leucocytes. Although it has been shown to inhibit "macroscopic" inflammatory processes in animal models, its direct effects on antigen-activated human T cells have not been studied. OBJECTIVE: To test the hypothesis that ANXA1-derived peptides inhibit antigen-driven prototype Th1 and Th2-type human T cell responses of clinical relevance and lectin-driven responses in vitro. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 14 atopic subjects sensitized to house dust mite allergen (Dermatophagoides pteronyssinus, Der p) and purified protein derivative (PPD) of Mycobacterium tuberculosis. PBMC (1 x 106/mL) were cultured with phytohaemagglutinin (PHA; 5 microg/mL; 4 days), Der p (25 microg/mL; 6 days), PPD (10 microg/mL, 6 days) or medium control. Two ANXA1-derived peptides, Ac2-26 and AF-2 (5-500 microM), were assessed for possible inhibition of PHA-and antigen-induced T cell proliferation (measured by 3H-thymidine uptake), while Ac2-26 was assessed for inhibition of Der p-induced interleukin (IL)-5 release and PPD-induced interferon-gamma (IFN-gamma) release (measured by ELISA). Comparison was made with dexamethasone as an established inhibitory control. Endogenous production by PBMC of cell surface-associated and intracellular ANXA1 in response to PHA, Der p and PPD in the presence and absence of dexamethasone was measured by specific ELISA. RESULTS: Both PHA- and antigen-induced T cellular proliferation were inhibited by dexamethasone. Although neither ANXA1-derived peptide significantly altered PHA-induced proliferation, both effected concentration-dependent reductions in antigen-induced proliferation, Ac2-26 being the more potent. Peptides of identical amino acid composition to Ac2-26 and AF-2, but of random sequence, were ineffective at equivalent concentrations. In addition, Ac2-26 and dexamethasone inhibited Der p-induced IL-5 release and PPD-induced IFN-gamma release in a concentration-dependent fashion. Endogenous ANXA1 was detectable in PBMC, but at concentrations approximately 104-fold lower, in molar terms, than the effective concentrations of the exogenously added, ANXA1-derived inhibitory peptides. Endogenous production was not significantly altered by any of the T cell stimuli employed in this study, in the presence or absence of dexamethasone. CONCLUSION: In prototype Th1 and Th2-type human T cell responses, ANXA1-derived peptides can inhibit antigen-driven cellular proliferation and cytokine production.     

Induction of epithelial-mesenchymal transition (EMT) by hypoxia-induced lncRNA RP11-367G18.1 through regulating the histone 4 lysine 16 acetylation (H4K16Ac) mark

Hypoxia activates various long noncoding RNAs (lncRNAs) to induce the epithelial-mesenchymal transition (EMT) and tumor metastasis. The hypoxia/HIF-1α-regulated lncRNAs that also regulate a specific histone mark and promote EMT and metastasis have not been identified. We performed RNA-sequencing dataset analysis to search for such lncRNAs and lncRNA RP11-367G18.1 was the hypoxia-induced lncRNA with the highest hazard ratio. High expression of lncRNA RP11-367G18.1 is correlated with a worse survival of head and neck cancer patients. We further showed that lncRNA RP11-367G18.1 is induced by hypoxia and directly regulated by HIF-1α in cell lines. Overexpression of lncRNA RP11-367G18.1 induces the EMT and increases the in vitro migration and invasion and in vivo metastatic activity. Knockdown experiments showed that lncRNA RP11-367G18.1 plays an essential role in hypoxia-induced EMT. LncRNA RP11-367G18.1 specifically regulates the histone 4 lysine 16 acetylation (H4K16Ac) mark that is located on the promoters of two “core” EMT regulators, Twist1 and SLUG, and VEGF genes. These results indicate that lncRNA RP11-367G18.1 regulates the deposition of H4K16Ac on the promoters of target genes to activate their expression. This report identifies lncRNA RP11-367G18.1 as a key player in regulating the histone mark H4K16Ac through which activates downstream target genes to mediate hypoxia-induced EMT.     

Sézary综合征1例报告及文献复习

目的归纳、分析S啨zary综合征的临床表现特征,提高对该病的诊疗水平。方法报告1例S啨zary综合征患者,并复习相关文献。结果患者男59岁,以全身皮肤潮红伴瘙痒为主要特征,外周血淋巴细胞达171.9×109/L,骨髓中异常淋巴细胞达33.5%,经大剂量糖皮质激素等治疗后缓解。1994年至今国内共报道11例S啨zary综合征患者,男性10例占90.9%,平均年龄56.9±19.1岁,以红皮病、剧痒为显著皮肤表现。结论S啨zary综合征是一种较罕见的T细胞淋巴瘤,多见于老年男性,早期皮肤损害显著但不典型,易被误诊为神经性皮炎、湿疹等。     

Impact of Adapted Physical Activity on Joint Pain Induced by Hormonotherapy in Adjuvant Breast Cancer Treatment: APAISE Study Protocol<br/>Impact de l’Activité Physique Adaptée sur les Douleurs Articulaires Induites sous Hormonothérapie en Traitement Adjuvant du Cancer : Protocole de l’Etude APAISE

Breast cancer is the most common cancer in women and approximately 80% of patients will receive hormone therapy. If survival rate after breast cancer patients is the most important, their treatment, induces strong side effects on quality of life, including joint pain which is encountered by one woman in two. These joint pains are likely to reduce compliance with the treatment and consequently impact survival. In this context, this work aims to evaluate the potential benefit of adapted physical activity to relieve pain and its impact on daily functions. The APAISE protocol, described in this article, is a prospective observational study carried out in women operated on for breast cancer and suffering from pain induced by hormone therapy (approximately 50 women followed up in 2 living areas). The main objective is to evaluate the evolution of pain in the context of an adapted physical activity supervised by a sports educator over a period of 3 months. In addition to pain and its interference, the other parameters studied are quality of life, therapeutic compliance and the level of physical activity. All these indicators will be measured at inclusion, at 3 months and at 6 months. In addition to an expected benefit on the well-being of patients, the results should shed light on the links between physical exercise and pain and in the long term reinforce recommendations in terms of physical activity in breast cancer patients.

Résumé
Le cancer du sein est le cancer le plus fréquent chez la femme, l’un de ceux qui présente le meilleur taux de survie, et pour lequel environ 80% des patientes recevront une hormonothérapie. Si les patientes présentent un pronostic de survie favorable, leur traitement hormonal induit des effets indésirables impactant sur la qualité de vie, parmi lesquels les douleurs articulaires rencontrées chez une femme sur deux. Ces douleurs articulaires sont susceptibles de diminuer l’observance au traitement et par conséquent d’impacter la survie. Dans ce contexte, ce travail vise à évaluer le bénéfice que pourrait présenter l’activité physique adaptée pour soulager ces douleurs et leur retentissement. Le protocole APAISE, décrit dans cet article, est une étude observationnelle prospective menée chez des femmes opérées d’un cancer du sein présentant des douleurs induites par hormonothérapie (environ 50 patientes suivies dans 2 bassins de vie). L’objectif principal est d’évaluer l’évolution des douleurs dans le cadre d’une activité physique adaptée encadrée par un éducateur sportif sur une durée de 3 mois. Outre la douleur et son retentissement, les autres paramètres étudiés sont la qualité de vie, l’observance thérapeutique et le niveau d’activité physique. Tous ces indicateurs seront mesurés, à l’inclusion, à 3 mois et à 6 mois. Outre un bénéfice attendu sur le bien-être des patientes, l’étude vise à éclairer les liens entre l’exercice physique et la douleur et à long terme de renforcer les recommandations et préconisations en matière d’activité physique chez les femmes traitées pour un cancer du sein.     

结核疫苗的研究进展

结核病是由结核分枝杆菌引发的一种传染病。1882年,结核分枝杆菌(mycobacterium tuberculosis, Mtb)由Robert Koch发现,至今仍是致人类死亡主要病原体之一。更可怕是,多重耐药(MDR)和广泛耐药(XDR) Mtb患病率的明显增加。上世纪90年代,世界卫生组织(World Health Organization, WHO)宣布结核病处于全球性紧急状态。结核病的最佳预防措施是接种疫苗,但是卡介苗(bacille Calmette-Guérin,BCG)对成人的保护效力不完全。随着Mtb基因序列的检测成功,疫苗的研究取得了重大的进展,已经有十几种候选疫苗准备或已进人体临床试验阶段。当前热门的候选疫苗包括重组BCG疫苗、减毒Mtb活疫苗和亚单位疫苗等。本文将从这些方面进行综述。     

Acridine derivatives (PANHs,azaarenes) in raw,fried or grilled pork from different origins,and PANH formation during pork thermal processing

The aim of this work was to determine level of azaarenes (PANHs) in raw pork and to investigate their formation during meat frying or grilling, in particular to verify a suggestion that endogenous vitamin E might inhibit production of azaarenes. Azaarene concentration in raw pork samples from various origins ranged from 2.75 ng g⁻¹ to 3.69 ng g⁻¹ (2.75–2.93 ng g⁻¹ in meat of Polish Landrace pigs, 3.00–3.69 ng g^–1 in meat of hybrid Duroc × Polish Landrance pigs). PANH formation during frying of pork meat was not confirmed. On the other hand, PANHs were indeed formed during grilling; their levels ranged from 6.21 ng g⁻¹ to 8.08 ng g^–1. No inhibition influence of vitamin E on formation of PANHs on was found either in fried or grilled pork meat.     

Monoclonal antibodies differentially affect the interaction between the hemagglutinin of H9 influenza virus escape mutants and sialic receptors

To determine the receptor binding properties of various H9 influenza virus escape mutants in the presence and absence of antibody, sialyloligosaccharides conjugated with biotinylated polyacrylamide were used. A mutant virus with a L226Q substitution showed an increased affinity for the Neu5Acalpha2-3Galbeta1-4Glc. Several escape mutants viruses carrying the mutation N193D bound to Neu5Acalpha2-6Galbeta1-4GlcNAc considerably stronger than to Neu5Acalpha2-6Galbeta1-4Glc. Several monoclonal antibodies unable to neutralize the escape mutants preserved the ability to bind to the hemagglutinin as revealed by enzyme-linked immunosorbent assay. In each case, the bound monoclonal antibodies did not prevent the binding of the mutant HA to high affinity substrates and did not displace them from the virus binding sites. Together, these data suggest that amino acid changes selected by antibody pressure may be involved in the specificity of host-cell recognition by H9 hemagglutinin and in the ability of viruses with these mutations to escape the neutralizing effect of antibodies in a differential way, depending on the specificity of the host cell receptor. It may be important in the natural evolution of the H9 subtype, a plausible candidate for the agent likely to cause a future pandemic.     

Curative resection with endoscopic submucosal dissection of early gastric cancer in Helicobacter pylori-negative Ménétrier’s disease:A case report

BACKGROUND Adult-onset Ménétrier’s disease is strongly associated with Helicobacter pylori(H.pylori)infection and an elevated risk of carcinogenesis.Cases of early-stage gastric cancer developed in H.pylori-negative Ménétrier’s disease are extremely rare.We report a case of early gastric cancer in H.pylori-negative Ménétrier’s disease that was curatively resected with endoscopic submucosal dissection(ESD).CASE SUMMARY A 60-year-old woman was referred to our hospital after her medical examination detected anemia.Contrast-enhanced upper gastrointestinal(UGI)radiography revealed translucency of the nodule-aggregating surface with giant rugae.Blood tests showed hypoproteinemia and were negative for serum H.pylori immunoglobulin G antibodies.The 99mTc-DTPA-human serum albumin scintigraphy showed protein loss from the stomach.UGI endoscopy showed a 40-mm protruding erythematous lesion on giant rugae of the greater curvature of lower gastric body,suggesting early-stage gastric cancer due to Ménétrier’s disease.En bloc resection with ESD was performed for diagnosis and treatment.Histology of ESD showed well-differentiated tubular adenocarcinoma.The cancer was confined to the mucosa,and complete curative resection was achieved.Foveolar hyperplasia and atrophy of the gastric glands were observed in non-tumor areas,histologically corresponding to Ménétrier’s disease.Three years after ESD,gastric cancer had not recurred,and Ménétrier’s disease remained in remission with spontaneous regression of giant gastric rugae.CONCLUSION Complete curative resection was achieved through ESD in a patient with earlystage gastric cancer and H.pylori-negative Ménétrier’s disease.