Diffuse large B‐cell lymphoma (DLBCL) is a clinically heterogeneous entity, in which the first‐line treatment currently consists of an immuno‐chemotherapy regimen (R‐CHOP). However, around 30% of ...patients will not respond or will relapse. Overexpression of c‐MYC or p53 is frequently found in DLBCL, but an association with prognosis remains controversial, as for other biomarkers previously linked with DLBCL aggressivity (CD5, CD23, or BCL2). The aim of this study was to explore the expression of these biomarkers and their correlation with outcome, clinical, or pathological features in a DLBCL cohort. Immunohistochemical (c‐MYC, p53, BCL2, CD5, and CD23), morphological (‘starry‐sky’ pattern SSP), targeted gene panel sequencing by next‐generation sequencing (NGS), and fluorescence in situ hybridisation analyses were performed on tissue microarray blocks for a retrospective cohort of 94 R‐CHOP‐treated de novo DLBCL. In univariate analyses, p53 overexpression (p53high) was associated with unfavourable outcome (p = 0.04) and with c‐MYC overexpression (p = 0.01), whereas c‐MYC overexpression was linked with an SSP (p = 0.004), but only tended towards an inferior prognosis (p = 0.06). Presence of a starry‐sky morphology was found to be correlated with better survival in p53high DLBCL (p = 0.03) and/or c‐MYC‐positive DLBCL (p = 0.002). Furthermore, NGS data revealed that these three variables were associated with somatic mutations (PIM1, TNFRSF14, FOXO1, and B2M) involved in B‐cell proliferation, survival, metabolism, and immune signalling. Taken together, these results show that the SSP pattern seems to be a protective factor in high‐risk DLBCL subgroups and highlight cell death as a built‐in failsafe mechanism to control tumour growth.
Glioblastoma multiform (GBM) tumors are very heterogeneous, organized in a hierarchical pattern, including cancer stem cells (CSC), and are responsible for development, maintenance, and cancer ...relapse. Therefore, it is relevant to establish new GBM cell lines with CSC characteristics to develop new treatments. A new human GBM cell line, named R2J, was established from the cerebro-spinal fluid (CSF) of a patient affected by GBM with leptomeningeal metastasis. R2J cells exhibits an abnormal karyotype and form self-renewable spheres in a serum-free medium. Original tumor, R2J, cultured in monolayer (2D) and in spheres showed a persistence expression of CD44, CD56 (except in monolayer), EGFR, Ki67, Nestin, and vimentin. The R2J cell line is tumorigenic and possesses CSC properties. We tested in vitro the anticancer effects of sodium selenite (SS) compared to temozolomide TMZ. SS was absorbed by R2J cells, was cytotoxic, induced an oxidative stress, and arrested cell growth in G2M before inducing both necrosis and apoptosis via caspase-3. SS also modified dimethyl-histone-3-lysine-9 (H3K9m2) levels and decreased histone deacetylase (HDAC) activity, suggesting anti-invasiveness potential. This study highlights the value of this new GBM cell line for preclinical modeling of clinically relevant, patient specific GBM and opens a therapeutic window to test SS to target resistant and recurrent GBM.
Curve tracing occurs when a line is followed covertly to accomplish a task, for example, to determine whether two landmarks are on the same line or not (could Highway 61 take Robert Johnson from New ...Orleans to St Louis?). Previous work suggests that attention either moves along the curve, momentarily activating local representations of the curve during this process, leaving little or no trace of this activation once attention has passed, or attention spreads along the curve, resulting in an activated state along the entire portion of the curve that was traced. We re-examined this issue using event-related potentials. Curves to be traced were presented briefly to encourage a rapid deployment of attention. The curves started on the vertical midline and passed into the left or right visual field and terminated either on the vertical midline or at a lateral position. We measured a posterior contralateral negativity (relative to the visual field of the traced curve) that offset more rapidly when the curve was traced back to the midline than when it remained lateral. The results suggest that attention travels along the curve like fire on a fuse, with activation returning to baseline once the flame has passed.
Abstract We presented pure tones interspersed with white noise sounds to disrupt contour perception in an acoustic short-term memory (ASTM) experiment during which we recorded the ...electroencephalogram. The memory set consisted of seven stimuli, 0, 1, 2, 3, or 4 of which were to-be-remembered tones. We estimated each participant׳s capacity, K , for each set size and measured the amplitude of the SAN (sustained anterior negativity, an ERP related to acoustic short-term memory). We correlated their K slopes with their SAN amplitude slopes as a function of set size, and found a significant link between performance and the SAN: a larger increase in SAN amplitude was linked with a larger number of stimuli maintained in ASTM. The SAN decreased in amplitude in the later portion of the silent retention interval, but the correlation between the SAN and capacity remained strong. These results show the SAN is not an index of contour but rather an index of the maintenance of individual objects in STM. This article is part of a Special Issue entitled SI: Auditory working memory.
We observed how information about the structure of tone sequences modulates cortical responses in the context of a standard short‐term memory (STM) task. Participants heard two sequences of one, ...three, or five tones (203 ms on, 203 ms off) interspersed by a silent interval (2 s) and decided whether the sequences were the same or different. In experiment 1, sequence length was randomized between trials. During the first sequence, the amplitude of the auditory P2 was larger for the second tone in trials with three tones, and for the second and fourth tone in trials with five tones. We hypothesize the increase in P2 reflected a dynamic disambiguation process because these tones were predictive of a sequence longer than one or three tones. This hypothesis was supported by the absence of P2 amplitude modulation during the second sequence (when sequence length was known). In experiment 2, we blocked trials by sequence length to ensure the effects were not caused by some process related to encoding in STM. There was no P2 amplitude modulation in either the first or second sequences. Thus, tones 2 and 4 had a larger amplitude only when they provided new information about the length of the current tone sequence. To some extent, the auditory N1 also showed those modulations. Independent Component Analysis of the ERPs provided evidence the modulations in P2 amplitude could originate in auditory cortex. These results suggest a rapid dynamic adaptation of auditory cortical responses based on the local informativeness of auditory signals.
A novel paradigm reveals dynamic updating of anticipated auditory events in the human brain based on the contextual informativeness of auditory signals within rapid short sequences. Tones carrying information that disambiguated sequence length produced larger auditory N1 and P2 ERP amplitudes. This new paradigm has the potential to be useful in future studies of fundamental mechanisms of dynamic context updating as well as in clinical applications.
Summary We report the first case of composite lymphoma involving both mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL) with circulating villous lymphocytes. Morphological, ...immunohistochemical, immunophenotyping, as well as detailed genetic studies (fluorescence in situ hybridization, IGVH gene sequencing), were performed and confirmed the existence of 2 independent, unrelated tumor clones. The MCL component expressed IgMD λ , was CD5+, harbored a t(11;14)(q13;q32) involving CCND1 , and showed an unmutated VH1-18 gene rearrangement. The SMZL component expressed IgMD κ , was CD5−, showed a t(10;14)(q24;q32) and an unmutated VH3-7 gene rearrangement. Interestingly, this t(10;14) targeted the NFKB2 gene. Only a single other case of SMZL with t(10;14)/ NFKB2 has been reported. Taken together, these data indicate that the MCL and SMZL arose as a consequence of independent malignant transformation events within an antigen-naive B-cell population. This case highlights the importance of a multidisciplinary approach and tissue diagnosis in these complex situations.
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