Mise au point sur l'analyse par chromatographie par exclusion stérique en milieu aqueux de télomères de l'acide acrylique

In the case of water soluble polymers, the use of size exclusion chromatography (SEC) for the determination of the molecular weight involves numerous difficulties. In order to analyse and determine the molecular weight of acrylic acid telomers we have first tried to obtain a satisfactory and reproducible separation. In this particular case, low-molecular-weight standards are not commercially available. Therefore, we decided to prepare standards based on acrylic acid, either by telomerization with a fluorinated telogen or by polymerization with an initiator bearing a fluorinated group. A calibration curve was obtained from the standards. Telomers of acrylic acid with thioglycolic acid were analysed. This is a general method for determination of DP _n by SEC when there is no standard for the polymers. It can be used in a wide range of DP _n from 1 to 700.     

Kyste hydatique du foie ouvert dans la vésicule biliaire : à propos d’un cas

The opening in the intra hepatic bile ducts is the most common complication of hepatic hydatid cyst. The opening in the gallbladder is unusual.We report the case of a 65-year-old woman with complaints of right upper quadrant pain and fever. Various explorations have found a hydatid acute cholecystitis due to an opening of a hydatid cyst of the liver in the gallbladder. Treatment was surgical.     

Immunohistochemical analysis of c-erbB-2, Bcl-2, p53, p21WAF1/Cip1, p63 and Ki-67 expression in hydatidiform moles

Hydatidiform moles (HM) are characterized by an abnormal proliferating trophoblast with a potential for a malignant transformation. Similar to other human tumors, trophoblastic pathogenesis is likely a multistep process involving several molecular and genetic alterations. The study was performed to investigate the expression patterns of c-erbB-2 and Bcl-2 oncoproteins, p53, p21^WAF1/CIP1 and p63 tumor suppressor proteins and Ki-67 cell proliferation marker in HM.We conducted a retrospective study of 220 gestational products, including 39 hydropic abortions (HA), 41 partial HM (PHM) and 140 complete HM (CHM). The expression of c-erbB-2, Bcl-2, p53, p21^WAF1/CIP1, p63 and Ki-67 was investigated by immunohistochemistry on archival tissues. c-erbB-2 expression was observed in three PHM and 10 CHM. Bcl-2 immunostaining was significantly higher in PHM (61%) and CHM (70.7%) compared with HA (7.7%, p?=? 0.001 and p?<? 0.0001, respectively). p53 expression was stronger in CHM (73.6%) compared with PHM (24.4%, p < 0.0001) and HA (12.8%, p < 0.0001). p21^WAF1/CIP1 staining was observed as well in molar and non-molar gestations (p?>? 0.05). p63 immunoexpression was significantly described in CHM (85.7%) and PHM (78%) compared with HA (10.2%, p < 0.0001 and p = 0.0001, respectively). Ki-67 was significantly expressed in CHM (72.1%) compared with HA (46.2%, p = 0.005).Altered expression of Bcl-2, p53, p63 and Ki-67 reflects the HM pathological development. Immunohistochemical analysis is beneficial to recognize the HM molecular and pathogenic mechanisms. Furthermore, it could serve as a useful adjunct to conventional methods for refining HM diagnosis.     

Tumor‐induced myeloid‐derived suppressor cell subsets exert either inhibitory or stimulatory effects on distinct CD8+ T‐cell activation events

Tumor growth coincides with an accumulation of myeloid‐derived suppressor cells (MDSCs), which exert immune suppression and which consist of two main subpopulations, known as monocytic (MO) CD11b⁺CD115⁺Ly6G^?Ly6C^high MDSCs and granulocytic CD11b⁺CD115^?Ly6G⁺Ly6C^int polymorphonuclear (PMN)‐MDSCs. However, whether these distinct MDSC subsets hamper all aspects of early CD8⁺ T‐cell activation — including cytokine production, surface marker expression, survival, and cytotoxicity — is currently unclear. Here, employing an in vitro coculture system, we demonstrate that splenic MDSC subsets suppress antigen‐driven CD8⁺ T‐cell proliferation, but differ in their dependency on IFN‐γ, STAT‐1, IRF‐1, and NO to do so. Moreover, MO‐MDSC and PMN‐MDSCs diminish IL‐2 levels, but only MO‐MDSCs affect IL‐2Rα (CD25) expression and STAT‐5 signaling. Unexpectedly, however, both MDSC populations stimulate IFN‐γ production by CD8⁺ T cells on a per cell basis, illustrating that some T‐cell activation characteristics are actually stimulated by MDSCs. Conversely, MO‐MDSCs counteract the activation‐induced change in CD44, CD62L, CD162, and granzyme B expression, while promoting CD69 and Fas upregulation. Together, these effects result in an altered CD8⁺ T‐cell adhesiveness to the extracellular matrix and selectins, sensitivity to FasL‐mediated apoptosis, and cytotoxicity. Hence, MDSCs intricately influence different CD8⁺ T‐cell activation events in vitro, whereby some parameters are suppressed while others are stimulated.     

Modulation of CD8 T-cell activation events by monocytic and granulocytic myeloid-derived suppressor cells

Myeloid-derived suppressor cells are immature myeloid cells, consisting of a monocytic and a granulocytic fraction, that are known to suppress anti-tumor immune responses. Important targets of the immunosuppressive capacity of MDSC are CD8⁺ T cells, which are crucial cytotoxic effector cells in immunotherapeutic settings. CD8⁺ T-cell activation and differentiation comprises a well-orchestrated series of events, starting from early TCR-mediated signaling and leading to cytokine secretion, the expression of activation markers, proliferation and the differentiation into several subsets of effector and memory cells. In this review, we summarize the available data on how the production of reactive oxygen species, nitric oxide, the arginase-mediated depletion of l-arginine and Cystine depletion by MDSCs interfere with the signaling molecules necessary for normal CTL differentiation and activation.     

Cell senescence and telomere shortening induced by a new series of specific G-quadruplex DNA ligands

Telomeres of human chromosomes contain a G-rich 3'-overhang that adopts an intramolecular G-quadruplex structure in vitro which blocks the catalytic reaction of telomerase. Agents that stabilize G-quadruplexes have the potential to interfere with telomere replication by blocking the elongation step catalyzed by telomerase and can therefore act as antitumor agents. We have identified by Fluorescence Resonance Energy Transfer a new series of quinoline-based G-quadruplex ligands that also exhibit potent and specific anti-telomerase activity with IC50 in the nanomolar concentration range. Long term treatment of tumor cells at subapoptotic dosage induces a delayed growth arrest that depends on the initial telomere length. This growth arrest is associated with telomere erosion and the appearance of the senescent cell phenotype (large size and expression of beta-galactosidase activity). Our data show that a G-quadruplex interacting agent is able to impair telomerase function in a tumor cell thus providing a basis for the development of new anticancer agents.