Noninvasive detection of microsatellite instability in patients with endometrial cancer

Endometrial cancer; Liquid biopsy; Uterine aspirateCàncer d'endometri; Biòpsia líquida; Aspirat uteríCáncer de endometrio; Biopsia líquida; Aspirado uterinoThe analysis of mismatch repair proteins in solid tissue is the standard of care (SoC) for the microsatellite instability (MSI) characterization in endometrial cancer (EC). Uterine aspirates (UAs) or circulating-DNA (cfDNA) samples capture the intratumor heterogeneity and provide a more comprehensive and dynamic molecular diagnosis. Thus, MSI analysis by droplet-digital PCR (ddPCR) in UAs and cfDNA can provide a reliable tool to characterize and follow-up the disease. The UAs, paraffin-embedded tumor tissue (FFPE) and longitudinal plasma samples from a cohort of 90 EC patients were analyzed using ddPCR panel and compared to the SoC. A high concordance (96.67%) was obtained between the analysis of MSI markers in UAs and the SoC. Three discordant cases were validated as unstable by ddPCR on FFPE samples. Besides, a good overall concordance (70.27%) was obtained when comparing the performance of the ddPCR assay on UAs and cfDNA in high-risk tumors. Importantly, our results also evidenced the value of MSI analysis to monitor the disease evolution. MSI evaluation in minimally invasive samples shows great accuracy and sensitivity and provides a valuable tool for the molecular characterization and follow-up of endometrial tumors, opening new opportunities for personalized management of EC.Centro de Investigación Biomédica en Red de Cáncer, Grant/Award Numbers: CB16/12/00295, CB16/12/00328; Fundación Científica Asociación Española Contra el Cáncer, Grant/Award Numbers: FC_AECC PROYE19036MOR, 2018-AECC, INVES20051COLA; Fundación Instituto de Investigación Sanitaria de Santiago de Compostela; Instituto de Salud Carlos III and FEDER, Grant/Award Numbers: CM19/00087, CP20/00119, PI20/00969, PI20/01566, PI21/00990; Spanish Ministry of Economy and Innovation, Grant/Award Number: PID2019-104644RB-I0

Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of ayahuasca: a longitudinal study

Ayahuasca is an Amazonian psychoactive plant beverage containing the serotonergic 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting alkaloids (harmine, harmaline and tetrahydroharmine) that render it orally active. Ayahuasca ingestion is a central feature in several Brazilian syncretic churches that have expanded their activities to urban Brazil, Europe and North America. Members of these groups typically ingest ayahuasca at least twice per month. Prior research has shown that acute ayahuasca increases blood flow in prefrontal and temporal brain regions and that it elicits intense modifications in thought processes, perception and emotion. However, regular ayahuasca use does not seem to induce the pattern of addiction-related problems that characterize drugs of abuse. To study the impact of repeated ayahuasca use on general psychological well-being, mental health and cognition, here we assessed personality, psychopathology, life attitudes and neuropsychological performance in regular ayahuasca users (n = 127) and controls (n = 115) at baseline and 1 year later. Controls were actively participating in non-ayahuasca religions. Users showed higher Reward Dependence and Self-Transcendence and lower Harm Avoidance and Self-Directedness. They scored significantly lower on all psychopathology measures, showed better performance on the Stroop test, the Wisconsin Card Sorting Test and the Letter-Number Sequencing task from the WAIS-III, and better scores on the Frontal Systems Behavior Scale. Analysis of life attitudes showed higher scores on the Spiritual Orientation Inventory, the Purpose in Life Test and the Psychosocial Well-Being test. Despite the lower number of participants available at follow-up, overall differences with controls were maintained one year later. In conclusion, we found no evidence of psychological maladjustment, mental health deterioration or cognitive impairment in the ayahuasca-using group

Genomic profiling of uterine aspirates and cfDNA as an integrative liquid biopsy strategy in endometrial cancer

The incidence and mortality of endometrial cancer (EC) have risen in recent years, hence more precise management is needed. Therefore, wecombined di erent types of liquid biopsies to better characterize the genetic landscape of EC in a non-invasive and dynamic manner. Uterine aspirates (UAs) from 60 patients with EC were obtained during surgery and analyzed by next-generation sequencing (NGS). Blood samples, collected at surgery, were used for cell-free DNA (cfDNA) and circulating tumor cell (CTC) analyses. Finally, personalized therapies were tested in patient-derived xenografts (PDXs) generated from the UAs. NGS analyses revealed the presence of genetic alterations in 93% of the tumors. Circulating tumor DNA (ctDNA) was present in 41.2% of cases, mainly in patients with high-risk tumors, thus indicating a clear association with a more aggressive disease. Accordingly, the results obtained during the post-surgery follow-up indicated the presence of ctDNA in three patients with progressive disease. Moreover, 38.9% of patients were positive for CTCs at surgery. Finally, the e cacy of targeted therapies based on the UA-specific mutational landscape was demonstrated in PDX models. Our study indicates the potential clinical applicability of a personalized strategy based on a combination of different liquid biopsies to characterize and monitor tumor evolution, and to identify targeted therapiesThis work was supported by grants and support from the Instituto de Salud Carlos III (ISCIII) and FEDER (PI17/01919, PI17/02071), CIBERONC (CB16/12/00328), and the AECC (Grupos Estables de Investigacion 2018-AECC) to A.G.-M. and M.A.; Instituto de Salud Carlos III (ISCIII) and FEDER (PI16/00134), CIBERONC (CB16/12/00295), and the AECC (Grupos Estables de Investigacion 2018-AECC) to G.M.-B.; and the AECC to L.M.-R

Grecs et indigènes de la Catalogne à la mer Noire

Le programme de travail qui aboutit à ce livre s’inscrit dans le cadre du réseau d’excellence européen Ramses2, initié par la Maison méditerranéenne des sciences de l’homme. Une demi-douzaine de tables rondes ont réuni entre 2006 et 2008, d’un bout à l’autre de la Méditerranée (à Empúries, Aix-en-Provence, Palerme, Naples, Athènes), quelque soixante-dix chercheurs essentiellement français, italiens et espagnols, mais aussi anglais, grecs, bulgares, roumains, canadiens et russes. Il s’agissait d’étudier les rapports d’acculturation entre colons grecs et populations indigènes, en tenant compte des différences géographiques et chronologiques mais aussi de l’historiographie et des habitudes de recherche des diverses institutions. Les nombreuses communications qui ont jalonné les six tables rondes sont ici la plupart du temps précédées de textes introductifs. Une première partie, consacrée aux approches régionales, permet d’illustrer l’état de la recherche dans quelques régions choisies (autour d’Empuries, d’Himère, de Marseille, de Vélia, en Thrace et en mer Noire). La seconde partie, thématique, aborde un certain nombre de thèmes de recherche dans les régions précédentes, mais aussi dans d’autres régions du monde de la colonisation grecque. Le point de vue adopté dans ce livre est d’abord celui de la culture matérielle ; l’approche en est essentiellement archéologique. On se demandera par exemple quels sont les indices archéologiques qui permettent de dire si un site est habité par des Grecs, par des indigènes ou par une population “mixte”, et comment ces indices ont été appréciés selon les périodes et selon les régions. Beaucoup de communications présentent des synthèses régionales ou thématiques, mais une large place est faite également à des sites inédits, pour lesquels on n’a pas hésité à livrer une abondante documentation (plans, matériel de fouille). C’est en effet par le renouvellement de la documentation archéologique que nous pouvons espérer avancer dans la compréhension des rapports d’acculturation entre les colons grecs et les populations locales

Improving the Management of Endometrial Cancer Patients through the Use of Liquid Biopsy Analyses: A Case Report

Endometrial cancer (EC) is the 4th most common neoplasm of the female genital tract, with 15–20% of patients being of high risk of recurrence which leads to a significant decrease in patient survival. Current therapeutic options for patients with EC are poor, being the combined therapy of carboplatin and paclitaxel the standard of care, with limited efficacy. Therefore, new therapeutic options and better monitoring tools are needed to improve the management of the disease. In the current case report, we showcase the value of liquid biopsy analyses in a microsatellite instability EC patient with initially good prognosis that however underwent rapid progression disease within 6 months post-surgery; through the study of plasma cfDNA/ctDNA dynamics to assess the tumour evolution during treatment, as well as the study of the uterine aspirate as a valuable sample that captures the intra-tumour heterogeneity that allows a comprehensive genomic profiling of the disease to identify potential therapeutic options. Furthermore, preclinical models were generated at the time of tumour progression to assess the efficacy of the identified targeted therapies

Stroop, Letter-Number Sequency Task, WSCT and FrsBe means (standard deviation).

<p>The ANOVA column shows results for the main effect of <i>Group</i> (ayahuasca users vs. controls). df =  degrees of freedom. Ayahuasca = ayahuasca-using group. W-Words; C-Colors; IW-Color incongruent words; RI-Resistence to Interference. LNS = Letter-Number sequency; <i>N_tot</i>  =  number of total errors; <i>N_pers</i> = number of perseverative errors; <i>N_nonpers</i> = number of non-perseverative errors; <i>N_cat</i> = number of achieved categores; <i>Fail</i> = failures no maintain set.</p

Sociodemographic data as means (standard deviation) for age, years of education, employment and income and as frequencies for race, marital status and religion.

*<p> = <i>p</i><0.05;</p>**<p> = <i>p</i><0.01;</p>***<p> = <i>p</i><0.001 in the Student’s t test.</p>†<p> = <i>p</i><0.05;</p>††<p> = <i>p</i><0.01;</p>†††<p> = <i>p</i><0.001 in the χ2 test (comparison includes multiple categories).</p><p>Asterisks and crosses indicate <i>p</i> values for between group (ayahuasca vs. controls) Student’s t tests (age, education, employment and income) and χ2 tests (gender, race, marital status and religion) at baseline and at follow up for the Jungle and Urban samples. Aya. =  Ayahuasca-using group; Comp. =  comparison group.</p

TCI scales and subscales means (standard deviation).

<p>The ANOVA column shows results for the main effect of <i>Group</i> (ayahuasca users vs. controls). df =  degrees of freedom. Ayahuasca  =  ayahuasca-using group. HA = Harm Avoidance; HA1-Anticipatory Worry vs. Uninhibited Optimism; HA2-Fear of Uncertainty vs. Confidence; HA3-Shyness with Strangers vs. Gregariousness; HA4-Fatigability and Asthenia vs. Vigor; NS = Novelty Seeking; NS1-Exploratory Excitability vs. Stoic Rigidity; NS2-Impulsiveness vs. Reflection; NS3-Extravagance vs. Reserve; NS4-Disorderliness vs. Regimentation; RD = Reward Dependence; RD1-Sentimentality vs. Insensitivity; RD3-Attachment vs. Detachment; RD4-Dependence vs. Independence; P = Persistence; SD = Self-directedness; SD1-Responsibility vs. Blaming; SD2-Purposefulness vs. Lack of Goal-Direction; SD3-Resourcefulness; SD4-Self-Acceptance vs. Self-Striving; SD5-Congruent Second Nature; C = Cooperativeness; C1-Social Acceptance vs. Social Intolerance; C2-Empathy vs. Social Disinterest; C3-Helpfulness vs. Unhelpfulness; C4-Compassion vs. Revengefulness; C5-Integrated Conscience; ST = Self-Trascendence; ST1-Self-Forgetfulness vs. Self-Conscious Experience; ST2-Transpersonal Identification vs. Self-Isolation; ST3-Spiritual Acceptance vs. Rational Materialism.</p

SOI, PLT, and BIEPS means (standard deviation).

<p>The ANOVA column shows results for the main effect of <i>Group</i> (ayahuasca users vs. controls). df = degrees of freedom. Aya.  =  ayahuasca-using group. Transcendent-Transcendent dimension; Meaning-Meaning and purpose in life; Mission-Mission in life; Sacredness-Sacredness of life; Awareness Tragic-Awareness of the tragic.</p