22 research outputs found
The Novel TORC1/2 Kinase Inhibitor PQR620 Has Anti-Tumor Activity in Lymphomas as a Single Agent and in Combination with Venetoclax
The dynamics of Early Celtic consumption practices: a case study of the pottery from the Heuneburg
The Early Celtic site of the Heuneburg (Baden-Wuerttemberg, Germany) has long been understood as a hallmark of early urbanization in Central Europe. The rich collection of Mediterranean imports recovered from the settlement, the elite burials in its surroundings and the Mediterranean-inspired mudbrick fortification wall further point to the importance of intercultural connections with the Mediterranean as a crucial factor in the transformation of Early Iron Age societies. We describe a new facet of this process by studying the transformation of consumption practices, especially drinking habits, brought about by intercultural encounters from the late 7th to the 5th century BC through the analysis of organic remains in 133 ceramic vessels found at the Heuneburg using Organic Residue Analysis (ORA). During the Ha D1 phase, fermented beverages, including Mediterranean grape wine, were identified in and appear to have been consumed from local handmade ceramics. The latter were recovered from different status-related contexts within the Heuneburg, suggesting an early and well-established trade/exchange system of this Mediterranean product. This contrasts with the results obtained for the drinking and serving vessels from the Ha D3 phase that were studied. The consumption of fermented beverages (wine and especially bacteriofermented products) appears to have been concentrated on the plateau. The ORA analyses presented here seem to indicate that during this time, grape wine was consumed primarily from imported vessels, and more rarely from local prestigious fine wheel-made vessels. In addition to imported wine, we demonstrate the consumption of a wide variety of foodstuffs, such as animal fats (especially dairy products), millet, plant oils and waxy plants, fruit and beehive products as well as one or several other fermented beverage(s) that were probably locally produced. Through this diachronic study of vessel function from different intra-site contexts, we inform on changing and status-related practices of food processing and consumption
Possible adverse events in children treated by manual therapy: a review
BACKGROUND: Pediatric manual therapy is controversial within the medical community particularly with respect to adverse events. Pediatric manual therapy (Ped MT) is commonly used by a number of professions such as chiropractors, osteopaths and naturopaths for a variety of treatments in children. Ped MT interventions range from advice, light touch, massage, through to mobilisation and high velocity spinal manipulation. However, current evidence related to adverse events associated with Ped MT is not well understood.
OBJECTIVE: To update the clinical research literature from the 2007 report by Vohra, Johnston, Cramer and Humphreys on possible adverse events in children treated by spinal manipulation.
METHODS: A review of the clinical research literature from June 2004 until January 2010 as reported in MEDLINE, PubMed and PubMed Central for adverse events specifically related to the treatment of pediatric cases by manual therapy.
RESULTS: Only three new clinical studies, one systematic review with meta-analysis and one evidence report were identified. Two clinical studies reported on chiropractic care and one on osteopathic spinal manipulation in children. The systematic review investigated all studies of adverse events and manual therapy and was not specific for pediatric patients. The evidence review focused on effectiveness of spinal manipulation in a variety of musculoskeletal conditions. No serious or catastrophic adverse events were reported in the clinical studies or systematic review. However for adults, it has been estimated that between 0.003% and 0.13% of manual therapy treatments may result in a serious adverse event. Although mild to moderate adverse events are common in adults, an accurate estimate from high quality pediatric studies is currently not available.
CONCLUSIONS: There is currently insufficient research evidence related to adverse events and manual therapy. However, clinical studies and systematic reviews from adult patients undergoing manual therapy, particularly spinal manipulation report that mild to moderate adverse events are common and self limiting. However serious adverse events are rare and much less than for medication commonly prescribed for these problems. More high quality research specifically addressing adverse events and pediatric manual therapy is needed
Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas
Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity
Identification clinique par spectrométrie de masse MALDI-TOF des champignons filamenteux : construction de banques de données pour les dermatophytes et les<em> Fusarium</em>
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Douleur épididymo-testiculaire chronique et syndrome de la charnière dorso-lombaire de Maigne
Follicular helper-T cells restore CD8+-dependent antitumor immunity and anti-PD-L1/PD-1 efficacy
BACKGROUND: T follicular helper cells (Tfh) are essential to shape B cell response during germinal center formation. Tfh accumulation has been reported in various human cancers, with positive or negative prognostic roles. However, the mechanisms explaining the accumulation of Tfh and their role in cancer remain obscure. METHODS: In vitro differentiated and mouse cell sorted Tfh phenotype was evaluated by flow cytometry and quantitative PCR (qPCR). Antitumor effect of Tfh was evaluated by adoptive transfer in different tumor-bearing mice models. The involvement of immune cells, cytokines and chemokines was evaluated, using depleting antibodies. Chemokines and cytokines expression and production were evaluated by qPCR and ELISA. In human, the impact of immune cells and chemokines on survival was evaluated by analyzing transcriptomic data from public databases and from our own patient cohorts. RESULTS: In this study, we show that Tfh exert an antitumor immune effect in a CD8+-dependent manner. Tfh produce interleukin-21, which sustains proliferation, viability, cytokine production and cytotoxic functions of exhausted T cells. The presence of Tfh is required for efficacy of antiprogrammed cell death ligand-1 therapy. Tfh accumulate in the tumor bed and draining lymph nodes in different mouse cancer models. This recruitment is due to the capacity of transforming growth factor β to drive Chemokine (C-X-C motif) Ligand 13 expression, a chemoattractant of Tfh, by intratumor CD8+ T cells. Accumulation of Tfh and exhausted CD8+ T cells predicts cancer outcome in various cancer types. In patients treated with anti-programmed cell death-1 mAb, accumulation of Tfh and CD8+ at the tumor site is associated with outcome. CONCLUSION: This study provides evidence that CD8+/Tfh crosstalk is important in shaping antitumor immune response generated by immunotherapy