Inhibition of the membrane repair protein annexin-A2 prevents tumor invasion and metastasis.

Cancer cells are exposed to major compressive and shearing forces during invasion and metastasis, leading to extensive plasma membrane damage. To survive this mechanical stress, they need to repair membrane injury efficiently. Targeting the membrane repair machinery is thus potentially a new way to prevent invasion and metastasis. We show here that annexin-A2 (ANXA2) is required for membrane repair in invasive breast and pancreatic cancer cells. Mechanistically, we show by fluorescence and electron microscopy that cells fail to reseal shear-stress damaged membrane when ANXA2 is silenced or the protein is inhibited with neutralizing antibody. Silencing of ANXA2 has no effect on proliferation in vitro, and may even accelerate migration in wound healing assays, but reduces tumor cell dissemination in both mice and zebrafish. We expect that inhibiting membrane repair will be particularly effective in aggressive, poor prognosis tumors because they rely on the membrane repair machinery to survive membrane damage during tumor invasion and metastasis. This could be achieved either with anti-ANXA2 antibodies, which have been shown to inhibit metastasis of breast and pancreatic cancer cells, or with small molecule drugs.

TEGDMA modulates glutathione transferase P1 activity in gingival fibroblasts.

Dental resinous materials can contain large amounts (from 30 to 50%) of triethylene-glycol-dimethacrylate (TEGDMA). This compound leaches into aqueous media and is toxic to dental pulp, as well as to gingival fibroblasts in vitro. To elucidate the mechanism of TEGDMA toxicity, we investigated the effects on glutathione (GSH) level and glutathione transferase P1 (GSTP1) activity in cultured human gingival fibroblasts. TEGDMA cytotoxic concentrations (from 0.5 to 2 mM) induced a depletion of GSH without formation of oxidized GSH (GSSG). In fibroblasts expressing the wild-type GSTP1, TEGDMA both inhibited and potentiated GSTP1 activity at high (IC50 = 1.1 mM) and low concentrations, respectively. In contrast, cells expressing the GSTP1 *A/*B variant showed a weak inhibition of GST activity only, associated with greater sensitivity to drug toxicity. Biochemical analysis of GSTP1 inhibition revealed that TEGDMA is a non-competitive antagonist with respect to GSH and substrate. Thus, TEGDMA interference with GSH and GSTP1 activity may contribute to dental-resin-induced adverse effects.

Adsorption of Glycosidic Surfactants at the Mercury Electrode

The adsorption of glycosidic surfactants from aqueous electrolyte solutions on a mercury electrode was studied by means of differential capacitive measurements (tensammetric method). The adsorption behavior of the mono- and disaccharidic surfactants studied is discussed in relation to their micellar properties, in particular their respective critical micellar concentration (CMC). With monosaccharidic surfactants, a broad and bell-shaped peak is observed on the tensammetric curves and it suggests the formation of a monolayer called hemimicelle at the mercury electrode. For disaccharidic compounds, the split capacity peak observed at concentrations above the CMC suggests the formation of a multilayer of micelles throughout the electrical double layer.

[Caudal block in the surgical repair of vesico-renal reflux]. / Intérêt de l'anesthésie caudale dans la cure chirurgicale du reflux vésico-rénal.

One hundred and twenty children have benefited from surgical cure for vesico-renal reflux under loco-regional anesthesia per caudal way, with use of a mixed solution of Lidocaine 1%, Bupivacaine 0.5%, with Adrenaline, along with a complementary narcosis. During the per operative time: the subsequent analgesia and muscular relief have always been excellent and lasted long enough. The hemodynamic status always showed a perfect stability. As to the ventilation, no deleterious effect could be demonstrated. Per operative blooding is reduced and central temperature is more easily controlled. During the post-operative time: the caudal anesthesia has allowed to maintain an efficient analgesia during a mean period of 12 hours which has been considered as sufficient. All the children went quickly back to a normal digestive function. There was no complication relevant to this technique.

[Abortion and the use of anaesthesia. Observations after two years' experience (author's transl)]. / Anesthésie pour interruption volontaire de grossesse. Réflexion après deux ans d'activité.

The authors give an account of their experience of anaesthesia in 380 abortion cases. Two kinds of technique were used: --paracervical block: 10.2 p. cent of the cases, only one complication; --narco-analgesia: considered to be essential. Dextromoramide was the principal analgesic used, chosen for its pharmacodynamic properties. Three narcotic drugs used successively in conjunction with this were: propanidine, with this drug per-anaesthetic complications and post-operative vomiting proved excessive, C.T. 1341 considerably reduced the frequency of these complications, disodic penthiobarbital did not give rise to any problems.

PIP: The authors report on their experience with anesthesia in 380 cases of induced abortion. Paracervical block was used in 39 cases, (10.2%), with no complications. General anesthesia was used in 3 different ways: 1) narcoanalgesia combined with propanidid and dextromoramide, used on 103 women (21.1% of cases), resulted in a large number of cases of vomiting; 2) narcoleptoanalgesia with propanidid, dextromoramide and droperidol, used on 143 patients, (37.6%), resulted in fewer cases of vomiting; and, 3) narcoanalgesia with CT 1341 and dextromoramide, used on 79 patients, (20.7%), resulted in an even smaller number of cases of vomiting.