Impact of radiotherapy on survival in resected or unresectable anaplastic thyroid carcinomas, a Rare Cancer Network study.

PURPOSE: Anaplastic thyroid carcinomas (ATC) are a heterogenous group of tumors of overall dismal prognosis. We designed models to identify relevant prognostic factors of survival of irradiated ATC patients including radiotherapy modalities (field size, dose). MATERIAL AND METHODS: Between 2000 and 2017, 166 ATC patients' treatments were divided into surgery and postoperative radiotherapy (poRT) or definitive radiotherapy (RT). Multiple imputation approach was used for missing data. Prognostic factors were identified using Lasso-penalized Cox modelling and predicted risk scores were built. RESULTS: Patients undergoing RT (n=70) had more adverse patient and disease characteristics than those undergoing poRT (n=96). Corresponding median survival rates were 5.4 and 12.1 months, respectively. PoRT patients undergoing poRT more likely received extended-field radiotherapy with prophylactic nodal irradiation, but rather received platinum- vs. adriamycin-based chemoradiotherapy. Radiotherapy was conventionally fractionated, delivered >60Gy in 51.9% and 61.7% and used extended fields in 88.5% and 71.2% of patients with poRT or RT. Radiotherapy interruption rates for toxicity were similar in the two groups. The best poRT-group model identified age>45yo, PS≥1, pathologic tumor stage≥pT4b,>N1 and R2 resection as poor prognostic factors. The best RT-group model (C-index of 0.72) identified PS≥3,>N1 and extended-field radiotherapy with prophylactic nodal irradiation (as opposed to tumour-bed irradiation only) as poor prognostic factors. CONCLUSION: In patients undergoing poRT, radiotherapy parameters had little influence over their survival irrespective of patient, disease characteristics, and quality of resection. In patients undergoing RT, extended-field radiotherapy improved survival in addition to PS and nodal stage.

Efficacy and safety of hypofractionated stereotactic radiotherapy for brain metastases using three fractions: A single-centre retrospective study.

PURPOSE: Hypofractionated stereotactic radiotherapy (HFSRT) has become a standard of care for patients with a limited number of brain metastases (BM). An increasing number of linear accelerators (LA) are able to accurately perform HFSRT including VersaHD® (Elekta®) LA. The main aim of this study was to report clinical outcomes of BM treated by HFSRT using 3×7.7Gy on 70% isodose line in terms of local control (LC). PATIENTS AND METHODS: Between November 2016 and October 2018, all patients suffering from histologically-proven primary with one or several newly diagnosed BM treated by HFSRT were retrospectively included and evaluated. Patients who had received prior treatment by neurosurgery or cerebral radiotherapy were excluded. RESULTS: Among 44 patients, 61 BM were treated. With a median follow-up of 31.9 months, LC rates at 6 and 12 months were 93.2% and 90.9, respectively. Single-BM was independently predictive of LC (P=0.025) and overall survival (P=0.013). Acute toxicity rates were acceptable: 65.9% of patients had grade 1 and 2 and no acute grade 3 toxicity according to the NCI-CTCAE (version 5.0). Regarding delayed toxicity, one case (2.3%) of radionecrosis was confirmed by magnetic resonance spectroscopy. CONCLUSION: In our single-centre retrospective analysis, BM treatment by HFSRT delivered in three fractions showed a 12-month LC rate of 90.9% without major toxicities, which suggests safety and efficiency of this technique. However, longer-term follow-up and prospective studies are still needed to confirm these results.

Evolutionary dynamics of Waxy and the origin of hexaploid Spartina species (Poaceae).

We investigated the evolutionary dynamics of duplicated copies of the granule-bound starch synthase I gene (GBSSI or Waxy) within polyploid Spartina species. Molecular cloning, sequencing, and phylogenetic analyses revealed incongruences between the expected species phylogeny and the inferred gene trees. Some genes within species were more divergent than expected from ploidy level alone, suggesting the existence of paralogous sets of Waxy loci in Spartina. Phylogenetic analyses indicate that this paralogy originated from a duplication that occurred prior to the divergence of Spartina from other Chloridoideae. Gene tree topologies revealed three divergent homoeologous sequences in the hexaploid S. alterniflora that are consistent with the proposal of an allopolyploid origin of the hexaploid clade. Waxy sequences differ in insertion-deletion events in introns, which may be used to diagnose gene copies. Both paralogous and homoeologous coding regions appear to evolving under selective constraints.

Effect of matrix metalloprotease inhibitors on the 95 kDa metallopeptidase of Candida albicans.

A 95 kDa metallopeptidase of Candida albicans could be involved in the process of dissemination of the yeast. Matrix metalloproteases (MMPs) are also responsible for collagen breakdown in inflammatory and malignant processes. We tested six compounds on the C. albicans enzyme. Doxycycline, gentamicin, cefalothin, galardin, and elaidic and oleic acids are known for their capacity to inhibit some MMPs. Amongst these agents, only oleic acid was able to markedly inhibit the purified metallopeptidase at very low concentrations. Moreover, this fatty acid inhibited the secretion of the enzyme in the culture medium without altering the yeast viability.

Detection of myosin immunoanalogue in the yeast Candida albicans.

Detection and localization of myosin immunoanalogue protein in the yeast Candida albicans were achieved by immunoblotting, indirect immunofluorescence assay, and immunoelectron microscopy. A polypeptide with an M(r) about 110,000, from cytosolic extract and insoluble fraction in the corresponding membrane pellet, was reacted with polyclonal and monoclonal antibodies raised against vertebrate muscle myosin. This protein was located by immunofluorescence and immunoelectron microscopy in the cell cortex along the plasmalemma, in the cytoplasm, and in the septum corresponding to bud scar region situated between the yeast-mother cell and the bud.

[Critical study of ELISA technique and high sensitivity direct agglutination test for the screening of antitoxoplasma IgG]. / Etude critique d'une technique ELISA et d'un test d'agglutination directe haute sensibilité pour le dépistage des IgG antitoxoplasmiques.

The authors have evaluated an ELISA (Toxo-IgG EIA; bioMérieux) and a direct agglutination test using a sensitized antigen (Toxo-Screen DA; bioMérieux), with a fluorescent test antibody (Toxo-Spot IF; bioMérieux) as a reference for the screening of toxoplasmosis IgG antibodies. A good correlation was obtained for these two methods with fluorescent test antibody (p less than 0.00001) on 841 sera. However, results obtained with direct agglutination test were better than those obtained with ELISA (direct agglutination versus fluorescent test antibody: 97.4% of agreement; ELISA versus fluorescent test antibody: 96.1% of agreement). In addition, the use of the Receiver Operating Characteristic (ROC) curve, showing the changes of sensitivity and specificity as a function of the possible values of each threshold, indicated that sera with titers between 15-20 IU/ml should be interpreted very cautiously.

[Amoebic keratitis caused by Acanthamoeba sp. May HSV1 infection play a role?]. / Kératite amibienne à Acanthamoeba sp. L'infection par HSV1 aurait-elle un rôle?

Many cases of human keratitis with Acanthamoeba sp. have a pseudo-herpetic appearance. The authors therefore evaluated the importance of co-infection with this virus in the onset of amoebic cornean lesions. After herpetic and amoebic co-infection rabbits showed severe cornean lesions, the viral aspect of cornea received a specific treatment. The amoebic co-infection progressed unchecked with severe lesions until day 37 p.i., in which trophozoites and cysts were numerous. The possible favourising role of HSV1 and Acanthamoeba sp. co-infection may exist in humans, just as it certainly exists in the rabbit.

Fos and Jun oncogenes transactivate chimeric or native promoters containing AP1/GCN4 binding sites in plant cells.

The function of mammalian transcription factors of the leucine zipper class was investigated in leaf-derived protoplasts of tobacco. In transient expression experiments, Fos and Jun strongly activated chimeric promoters composed of the TATA box region of the cauliflower mosaic virus 35S transcript preceded by one to five copies of an AP1/GCN4 binding site. Fos and Jun also stimulated a wheat high molecular weight glutenin promoter in which similar binding sites are located more than 500 base pairs from its transcription start site. Both the DNA binding and the transcription activation domains of these proteins were required for proper promoter stimulation by Fos and Jun. Each factor alone was partially active, suggesting that at least the Fos protein can associate with an endogenous plant transcription factor. These observations support the hypothesis that sequences related to AP1/GCN4 binding sites could be cis-acting modules involved in the transcriptional regulation of plant genes.

Yeast RAS2 affects cell viability, mitotic division and transient gene expression in Nicotiana species.

Overexpression of the budding yeast RAS2 gene in Nicotiana plumbaginifolia cells revealed that RAS2 acted as 'suicide' gene in freshly isolated protoplasts from leaves and blocked cell proliferation in cell suspension-derived protoplasts. Among a series of genes tested (such as npt II, CDC35, PDE2), RAS2 was the only one to block the expression of the cat gene, as measured in a transient gene expression assay. Another ras gene, v-Ha-ras, had similar effects. Furthermore, the RAS2 effect was species-specific and depended on the modulation of hormonal metabolism in the transfected cells, while no differences were noticed between the normal and the activated val19 gene. Transfected plant cells are shown to synthesize a RAS2 protein of the same electrophoretic mobility as the yeast RAS2 product. The results are discussed in the broader context of the evolutionarily conserved ras genes involved in vital cellular functions.