Results of R-ESHAP as salvage therapy in refractory/relapsed follicular lymphoma: a real-world experience on behalf of GELCAB group.

There is no standard treatment for relapsed follicular lymphoma (FL). Although platinum-based combinations are one of the most used treatments, few data have been reported in this setting. Our aim was to analyse R-ESHAP efficacy in relapsed FL patients. We retrospectively analysed 80 FL patients treated with R-ESHAP in the first or successive relapses. Responding patients received a stem cell transplantation following R-ESHAP. Seventeen histologically transformed patients were included. Median age was 50 years. At R-ESHAP initiation, 85% of the patients were in an advanced stage, 28% had a bulky disease and 40% had increased LDH. There were no statistically significant differences between POD24 and non-POD24 patients in terms of response to R-ESHAP (ORR 72% vs. 93%, p = 0.109). When analyzing R-ESHAP efficacy according to the response to the immediately previous line, patients achieving CR or PR had better CR rates to R-ESHAP than those who did not respond (CR of 57% vs. 15%, respectively, p = 0.009), as well as differences in OS (7.2 vs. 1.4 years, p < 0.0001) and in PFS (2.1 vs. 0.3 years, p < 0.0001). R-ESHAP is an effective treatment in relapsed FL patients who respond to the previous line and has to be considered as an adequate alternative for some patients.

First total syntheses of aeruginosin 298-A and aeruginosin 298-B, based on a stereocontrolled route to the new amino acid 6-hydroxyoctahydroindole-2-carboxylic acid.

The first total syntheses of aeruginosin 298-A (1) and aeruginosin 298-B (3) are described. The syntheses of the alternative putative structures 2 and 4 were also accomplished. The key common strategic element is the stereo-controlled synthesis of (2S,3aS,6R,7aS)-6-hydroxyoctahydroindole-2-carboxylic acid (L-Choi, 5) from L-tyrosine. The synthesis of this new bicyclic alpha-amino acid, which is the core of aeruginosins, involves Birch reduction of O-methyl-L-tyrosine (6) and aminocyclization of the resulting dihydroanisole 7 in acid medium, followed by N-benzylation to give the diastereoisomers 12 and 13. Upon acid treatment with HCl-MeOH, the last two produce an equilibrium mixture in which the endo isomer 13 significantly predominates. Hydrogenation of 13 in the presence of (Boc)2O gives 16, which on reduction with LS-Selectride furnishes the alcohol 22, a protected L-Choi. Successive couplings of 22 with D-leucine, protected (R)-(4-hydroxyphenyl)lactic acid, and L-arginine fragments, followed by reduction to the argininol level and a deprotection end step complete the synthetic sequence to produce aeruginosin 298-A (1). Spectral comparison showed that peptide 2, with the structure previously proposed for aeruginosin 298-A, was different from the natural product. However, synthetic 1 was found to be identical to the isolated natural sample of aeruginosin 298-A. These results unequivocally establish that the absolute stereochemistry of aeruginosin 298-A, formerly assigned incorrectly, is D-Hpla-D-Leu-L-Choi-L-Argol, as shown by structure 1. Aeruginosin 298-B was also synthesized and shown to be a mixture of rotamers of D-Hpla-D-Leu-L-ChoiNH2 (3), rather than an epimeric mixture of 3 and the L-Leu-incorporating 4.

Ultra low-level gamma ray spectrometry of thorium in human bone samples.

Following the use of in vivo measurements of 210Pb to estimate retrospectively radon exposure, interest has been expressed in the use of in vivo measurements of 208Tl to estimate thorium intake. To aid with calibration and to determine the optimum part of the body on which in vivo measurements should be made, the distribution of 208Tl and 228Ac amongst different human bones was measured in the underground laboratory HADES. The 208Tl activity was determined by the 2614.5 keV and the 583.2 keV gamma ray lines. The 225Ac activity was determined by the 911.2 keV and the 969.0 keV gamma ray lines. The background under those peaks when measured on the 106% relative efficiency coaxial HPGe detector in HADES is of the order of 1 d(-1), resulting in detection limits in the order of 1 mBq for both radionuclides for a typical 10 g bone sample and for a measuring time of I week.

Measurements of activation induced by environmental neutrons using ultra low-level gamma-ray spectrometry.

The flux of environmental neutrons is being studied by activation of metal discs of selected elements. Near the earth's surface the total neutron flux is in the order of 10(-2) cm(-2)s(-1), which gives induced activities of a few mBq in the discs. Initial results from this technique, involving activation at ground level for several materials (W, Au, Ta, In, Re, Sm, Dy and Mn) and ultra low-level gamma-ray spectrometry in an underground laboratory located at 500 m.w.e., are presented. Diffusion of environmental neutrons in water is also measured by activation of gold at different depths.

Presence of blood group H antigen on a carcinoembryonic antigen, and its enzymatic modification into blood group A and B specificities.

A carcinoembryonic antigen (CEA-M) was purified from a hepatic metastasis obtained from a blood group O patient with cancer of the rectum. Using 125I-labeled carcinoembryonic antigen (CEA) and blood group antisera, H specificity has been found on the CEA-M. As the addition of anti-H to anti-CEA does not modify the extent of binding of labeled CEA-M to its antibodies (86%), the H and CEA determinants are carried by the same molecule. The affinity chromatography of CEA-M on an immunosorbent "anti-H-Sepharose" demonstrated that a proportion of CEA-M molecules might bear both H and CEA antigenic determinants. In addition, glycosyltransferases were used to modify the blood group H specificity into blood group A or B specificities.

Cordycepin and early effects of estradiol on the immature rat uterus.

Estradiol induces the synthesis of a specific protein fraction (IP) in the uterus of the immature rat. The injection of cordycepin (3' deoxyadenosine), an inhibitor of poly A synthesis, inhibits the synthesis of IP. This fact suggests that one of the earliest effects of estrogen is the production of Hn-RNA poly-A relative to IP. Moreover, using electron microscopy, the stimulation by estradiol of the nucleolus of the immature rat uterine epithelium has been shown. Cordycepin does not affect this stimulation to any appreciable extent. Biochemical studies (incorporation of radioactive stracers into NRA, affinity chromatography on poly U-Sepharose) carried out in parallel with and under conditions comparable to those used in electron microscopy show that cordycepin does not greatly affect the increase in ribosomal RNA observed under the effect of estradiol. The blocking of IP by cordycepin and the lack of inhibition at the nucleolus level under the same conditions, show that the two early effects of the action of estrogen on the immature rat uterus are not directly correlated.

Enzymatic modification of the transplant antigens (ABO system) on human tumor cells.

Blood group glycosyltransferases were used to modify HeLa cells of H specificity (O Group) into cells of A and B specificity. We also obtained the identical type of modification with lymphocytes from healthy subjects and leukemia patients. This method can be applied to tumor cells in general, and constitutes an attempt to stimulate the immunocompetent system.

[Presence of the H blood group antigen on a carcinoembryonic antigen (CEA). Enzymatic transformation of H to A and B specificities]. / Présence de l'antigène H de groupe sanguin sur un antigène carcino-embryonnaire (CEA). Modification enzymatique de la spécificité H en spécificité A et B

The carcinoembryonic antigen (CEA-M) was purified from a hepatic metastasis obtained from a blood group O patient with a cancer of the rectum. Using 125I-labelled-CEA and blood group antisera, H specificity was found on the CEA-M; the addition of anti-H to anti-CEA does not modify the binding of labelled-CEA-M to its antibodies (86%), this result leads us to conclude that H and CEA determinants are carried by the same molecule. However the low percentage of binding (30% with 1/10 anti-H) suggests that only a few CEA-M molecules do carry the H antigenic determinant. Finally, glycosyltransferases were used to modify the H specificity into blood group A and B specificities.

[Fluorescence study of lymphocyte plasma membranes]. / Etude par fluorescence des membranes plasmiques de lymphocytes

ANS binding parameters--dissociation constant, number of binding sites, rotation freedom--are measured by fluorescence studies of a complex between ANS and lymph node cell plasma membranes. Divalent ions, Mg++ and Ca++, enhance the complex fluorescence intensity without shifting its maximum wavelength : this enhancement is induced by affinity and quantum yield increases, while the number of binding sites remains constant. The complex fluorescence quenching by ethacrynic acid shows the presence of free SH groups in the ANS binding site. An energy transfer takes place between membrane protein tryptophan residues and bound ANS ; the energy transfer yield is unaffected by Ca++ ions. A correlation of these results is postulated with the biological activity of the membrane.