Combination therapy with irinotecan and cisplatin as neoadjuvant chemotherapy in locally advanced cervical cancer

To evaluate the response rate and toxicity of the combination of irinotecan (CPT-11) and cisplatin in a neoadjuvant setting, a phase II study was conducted regarding the regimen of this combination in patients with locally advanced cervical cancer. Eligibility included patients with previously untreated stage Ib2, IIb, or IIIb squamous cell carcinoma with good performance status. CPT-11 (60 mg m−2) was administered intravenously on days 1, 8 and 15, followed by cisplatin (60 mg m−2) given intravenously on day 1. Treatment was repeated every 4 weeks for a total of two or three cycles. Among 23 eligible patients (median age: 59 years), three showed complete response (13%), 15 showed partial response (65%), for an overall response rate of 78% (95% confidence interval 58–90%). Stable disease was observed in four cases (17%) and progressive disease in one (4%). The median time to failure and median survival time have not yet been reached. Of the 52 treatment cycles administered, diarrhoea and grade 3 or 4 neutropenia were observed in 10% and 75% respectively. There were no therapy-related deaths. The combination of CPT-11 with cisplatin is a promising regimen for neoadjuvant chemotherapy in locally advanced cervical cancer. The toxicities of this regimen are well tolerated. © 1999 Cancer Research Campaig

Rapid fucosylation of intestinal epithelium sustains host–commensal symbiosis in sickness

Systemic infection induces conserved physiological responses that include both resistance and ‘tolerance of infection’ mechanisms. Temporary anorexia associated with an infection is often beneficial, reallocating energy from food foraging towards resistance to infection or depriving pathogens of nutrients. However, it imposes a stress on intestinal commensals, as they also experience reduced substrate availability; this affects host fitness owing to the loss of caloric intake and colonization resistance (protection from additional infections). We hypothesized that the host might utilize internal resources to support the gut microbiota during the acute phase of the disease. Here we show that systemic exposure to Toll-like receptor (TLR) ligands causes rapid α(1,2)-fucosylation of small intestine epithelial cells (IECs) in mice, which requires the sensing of TLR agonists, as well as the production of interleukin (IL)-23 by dendritic cells, activation of innate lymphoid cells and expression of fucosyltransferase 2 (Fut2) by IL-22-stimulated IECs. Fucosylated proteins are shed into the lumen and fucose is liberated and metabolized by the gut microbiota, as shown by reporter bacteria and community-wide analysis of microbial gene expression. Fucose affects the expression of microbial metabolic pathways and reduces the expression of bacterial virulence genes. It also improves host tolerance of the mild pathogen Citrobacter rodentium. Thus, rapid IEC fucosylation appears to be a protective mechanism that utilizes the host’s resources to maintain host–microbial interactions during pathogen-induced stress

SHORT RANGE STRUCTURE AND SOME PHYSICAL PROPERTIES OF THE GLASSES IN THE SYSTEM Na2O-Ga2O3-SiO2

On a déterminé le domaine de formation vitreuse dans le système Na2O-Ga2O3-SiO2 et on a mesuré la densité, la dureté et le coefficient de dilatation thermique. On a trouvé que le domaine de formation vitreuse dans ce système est beaucoup plus étendu en comparaison de celui dans le système Na2O-Al2O3-SiO2. Les propriétés ont montré un changement brusque lorsque rapport Ga/Na = 1. Cette anomalie est analogue à celle observée dans le système Na2O-Al2O3-SiO2. Les résultats des mesures des spectres IR, des spectres d'émission des rayons X et des spectres de diffraction des rayons X suggèrent que des oxygènes non pontants existant dans les verres de silicate de sodium se transforment en oxygènes pontants avec l'addition de Ga2O3 pour des rapports Ga/Na inférieurs à l'unité, et que des oxygènes non pontants apparaissent de nouveau avec la formation du liaison Ga-O-Ga lors de l'addition supplémentaire de Ga2O3 lorsque le rapport Ga/Na > 1.The glass-forming region in the system Na2O-Ga2O3-SiO2 was determined, and the density, hardness and thermal expansion coefficient were measured. The glass-forming region in this system was found to be much wider than that in the Na2O-Al2O3-SiO2 system. The properties showed a sudden change at the composition of Ga/Na ratio 1. This anomaly is similar to that observed in the Na2O-Al2O3-SiO2 system. The results of IR spectra, X-ray emission spectra and X-ray diffraction patterns suggest that the non-bridging oxygens existing in sodium silicate glasses change into bridging oxygens with the addition of Ga2O3 at Ga/Na ratio less than 1 and then appear again along with the formation of Ga-O-Ga bond with further addition of Ga2O3 over the Ga/Na ratio of 1