PD-L1 expression with QR1 and E1L3N antibodies according to histological ovarian cancer subtype: A series of 232 cases

Therapeutic strategies for epithelial ovarian cancers are evolving with the advent of immunotherapy, such as PD-L1 inhibitors, with encouraging results. However, little data are available on PDL-1 expression in ovarian cancers. Thus, we set out to determine the PD-L1 expression according to histological subtype. We evaluated the expression of two PD-L1 clones – QR1 and E1L3N – with two scores, one based on the percentage of labeled tumor cells (tumor proportion score, TPS) and the other on labeled immune cells (combined proportion score, CPS) in a consecutive retrospective series of 232 ovarian cancers. PD-L1 expression was more frequent in high grade serous carcinoma (27.5% with E1L3N clone and 41.5% with QR1 clone), grade 3 endometrioid carcinoma (25% with E1L3N clone and 50% with QR1 clone), and clear-cell carcinomas (27.3% with E1L3N clone and 29.6% with QR1 clone) than other histological subtypes with CPS score. Using the CPS score, 17% of cases were labeled with E1L3N vs 28% with QR1. Using the TPS score, 14% of cases were positive to E1L3N vs 17% for QR1. For TPS and CPS, respectively, 77% and 78% of the QR1 cases were concordant with E1L3N for the thresholds of 1%. Overall and progression-free survival between PD-L1 positive and PD-L1 negative patients were not different across all histological types, and each subtype in particular for serous carcinomas expressing PD-L1. Expression of PD-L1 is relatively uncommon in epithelium ovarian tumors. When positive, usually <10% of tumor cells are labeled. QR1 clone and CPS appear the best tools to evaluate PD-L1 expression.Key words: Ovarian cancer, PD-L1 antibody, immunochemistry, histological subtype     

Lessons from human teratomas to guide development of safe stem cell therapies

The potential for the formation of teratomas or other neoplasms is a major safety roadblock to clinical application of pluripotent stem cell therapies. Preclinical assessment of the risk of tumor formation in this context poses considerable scientific and regulatory challenges, especially because animal xenograft models may not properly reflect the long-term tumorigenic potential of human cells. A better understanding of the biology of spontaneously occurring teratomas and related tumors in humans can help to guide efforts to assess and minimize the potential hazards of embryonic stem cell or induced pluripotent stem cell therapeutics. Here we review the features of teratomas derived experimentally from human pluripotent stem cells and argue that they most closely resemble spontaneous benign teratomas that occur early in both mouse and human life. The natural history and pathology of these spontaneously occurring teratomas provide important clues for preclinical safety assessment and patient monitoring in trials of stem cell therapies.     

The Synthesis of 125I-2-Iodohistamine for Radioimmunoassay1

Abstract

Recently radioactively labeled iodohistamines have been claimed to have superior shelf-life to the iodophenols more commonly used in radioimmunoassay of small molecules. This claim is based largely on theoretical considerations; no systematic study has appeared. We found that iodination of histamine on macroscale proceeds rapidly at pH 7–8.4 to yield principally 2-iodohistamine. With large excess of iodine, substantial diiodi-nation can be achieved. In 0.5 N sodium hydroxide solution, tri-iodination produces 1,2,5-triiodohistamine; the N-I bond, how-ever, is somewhat labile. ¹²⁵I-2,5-Diiodohistamine is also some-what unstable, having first order decomposition rate of 1.6 × 10^?3 day^?1 (t^1/2, 182 days), while ¹²⁵I-2-iodohistamine shows barely perceptible change in 60 days (7.5 × 10^?5 day^?1) The assignment of the first iodine introduced to C-2 is based on a comparison of the NMR spectra of monoiodohistamine and histamine. Iodination with carrier-free iodine-125 using the Hunter-Greenwood procedure (chloramine-T) produces a 76% yield of mono- and a 19% yield of diiodo product which are easily isolable by a single TLC using silica gel in the solvent system, ethano1:ethyl ether:water, 5:5:2.

Nothing has appeared on the chemistry of iodination of histamine. Since the proposal of Jeffcoate et al.⁴ that iodohistamines might be more stable than iodophenols, notably iodotyrosine derivates, a number of investigators have used ¹²⁵I-iodohistamines for the radioimmunoassay of estradiol-17β⁵, progesterone^6–9, norethisterone^6,10,11, testosterone⁶ and bile acids¹². Usually an undefined mixture of iodohistamines has been coupled to the assay ligand.

In this paper we report the preparation of standards (2-, 2,5- and l,2,5-iodohistamines) and the effect of experimental parameters on the synthesis of ¹²⁵I-2-iodohistamine and ²⁵¹I-2,5-diiodohistamine.     

Marine fungal abilities to enzymatically degrade algal polysaccharides,proteins and lipids: a review

Journal of Applied Phycology - Over the last decades, metabolites with biotechnological application produced by marine resources and notably macroalgae have seen increasing interest. Among these...     

Spatial coupling between DNA replication and mismatch repair in Caulobacter crescentus

The DNA mismatch repair (MMR) process detects and corrects replication errors in organisms ranging from bacteria to humans. In most bacteria, it is initiated by MutS detecting mismatches and MutL nicking the mismatch-containing DNA strand. Here, we show that MMR reduces the appearance of rifampicin resistances more than a 100-fold in the Caulobacter crescentus Alphaproteobacterium. Using fluorescently-tagged and functional MutS and MutL proteins, live cell microscopy experiments showed that MutS is usually associated with the replisome during the whole S-phase of the C. crescentus cell cycle, while MutL molecules may display a more dynamic association with the replisome. Thus, MMR components appear to use a 1D-scanning mode to search for rare mismatches, although the spatial association between MutS and the replisome is dispensible under standard growth conditions. Conversely, the spatial association of MutL with the replisome appears as critical for MMR in C. crescentus, suggesting a model where the β-sliding clamp licences the endonuclease activity of MutL right behind the replication fork where mismatches are generated. The spatial association between MMR and replisome components may also play a role in speeding up MMR and/or in recognizing which strand needs to be repaired in a variety of Alphaproteobacteria.     

Monogeneans from <Emphasis Type="Italic">Epinephelus chlorostigma</Emphasis> (Val.) (Perciformes: Serranidae) off New Caledonia,with the description of three new species of diplectanids

Gill monogeneans from the brownspotted grouper Epinephelus chlorostigma (Val.) collected in deep water off the coral barrier reef of New Caledonia, South Pacific, comprise seven species. These include the ancyrocephalid Haliotrema sp., the capsalid Allobenedenia cf. epinepheli Yamaguti, 1968, and five diplectanids, namely Pseudorhabdosynochus epinepheli (Yamaguti, 1938), reported in a previous paper, P. cyanopodus Sigura & Justine, 2008 and P. podocyanus Sigura & Justine, 2008, two species originally described from E. cyanopodus Richardson, P. stigmosus n. sp., P. exoticoides n. sp. and Diplectanum femineum n. sp. P. stigmosus is characterised by a sclerotised vagina with a straight primary canal, large ovoid primary chamber and spherical secondary chamber. P. exoticoides is a highly aberrant species, with a thick-walled male quadriloculate organ and a discoid sclerotised vagina with an exceptional structure. Interestingly, P. exoticoides resembles P. exoticus Sigura & Justine, 2008, a species from E. cyanopodus, and P. stigmosus resembles P. cyanopodus and P. podocyanus, also both from E. cyanopodus, suggesting close relationships between the diplectanid faunae of these two fish species. D. femineum belongs to a group of diplectanids, provisionally classified as ‘Diplectanum’ Diesing, 1858, which all share a small funnel-shaped male copulatory organ. In contrast to other members of this group which have no sclerotised vagina, D. femineum has a sclerotised vagina with the same organisation as those of species of Pseudorhabdosynochus Yamaguti, 1958. This suggests that the species of ‘Diplectanum’ from groupers are closer to Pseudorhabdosynochus than suggested by the structure of the male organs.     

Microcotyle visa n. sp. (Monogenea: Microcotylidae), a gill parasite of Pagrus caeruleostictus (Valenciennes) (Teleostei: Sparidae) off the Algerian coast,Western Mediterranean

Parasite biodiversity of fish of the southern part of the Mediterranean sea is still incompletely explored. We describe here Microcotyle visa n. sp. from the gill filaments of the bluespotted seabream Pagrus caeruleostictus (Valenciennes) (Sparidae) collected off the Algerian coast. The identity of fish hosts was confirmed by barcoding. Microcotyle visa n. sp. is herein described and illustrated. Analysis of the cox1 gene of the monogeneans revealed minor intraspecific variation (1.4%), an order of magnitude lower than the distance between this species and other Microcotyle species (10–15 %). Microcotyle visa n. sp. is distinguished from Microcotyle erythrini van Beneden & Hesse, 1863, a congener infesting sparids, on the basis of morphological (size of clamps, number of testes) and molecular (cox1) differences. This is the fourth member of the genus known to parasitise a sparid host. A species of Paramicrocotyle sp. included in the molecular analysis was nested within a robust Microcotyle + Paramicrocotyle clade; in the absence of demonstrated molecular and morphological differences, we consider that Paramicrocotyle Caballero & Bravo-Hollis, 1972 is a junior synonym of Microcotyle van Beneden & Hesse, 1863 and transfer two species of Paramicrocotyle as Microcotyle danielcarrioni (Martinez & Barrantes, 1977) n. comb. and Microcotyle moyanoi (Villalba & Fernandes, 1986) n. comb.