Biology subjects

Toth, E.

Publications and source records attributed to Toth, E..

At least 19 recordsLinked to original sources

bioRxiv2026

The 'false transience' hypothesis: Do we need to reconsider the seed persistence classifications of soil seed bank studies?

Background and Aims Seed bank persistence data is typically indirect, inferred from the presence and distribution of seeds in the soil. However, this approach frequently underestimates seed longevity, because dormant and low-abundance seeds can remain undetected. Here, we introduce and test the 'false transience' hypothesis which proposes that a subset of species classified as having transient seeds based on soil seed bank (SSB) studies actually possess the capacity for long-term persistence. Their perceived transience stems from methodological limitations and ecological filters, rather than physiological constraints. We also aimed to assess how the seed mass and seed production of 'false transient' species compare to the full range of tested species. Methods We focused on species considered to have transient seeds based on SSB studies. We conducted a germination experiment with 103 species using dry-stored seeds aged 10-29 years. We then assessed how the seed mass and seed number of germinating species relate to the full range of tested species. Key Results From the 103 tested species, eight species (~8%) germinated. The majority of species germinating after >10 years had large seeds and low seed numbers compared to the full range of species, and all germinating species had seed numbers below the median of the tested species. Conclusions Our results provide partial support for the proposed 'false transience' hypothesis, showing that nearly 10% of supposedly transient species can persist after more than a decade of ex situ storage. Our results also suggest that 'false transients' are frequently large-seeded with low seed production, therefore being more likely to be missed in SSB studies and erroneously classified as transient. We can conclude that relying solely on field SSB data to infer seed persistence can be misleading, suggesting that the widely observed negative relationship between seed size and persistence may also require reconsideration.

ecology↗

bioRxiv2025

Glia cells are selectively sensitive to nanosized titanium dioxide mineral forms

Nanosized titanium dioxide is widely used by the industry e.g. in pigments, suncreams and food colors. Its environmental and biological effects have been investigated in the past, however, few studies have focused on its crystal structure-specific effects. In our experiments, the toxicity of two types of nanoparticles was examined on primary neural cultures with different cell-compositions, using MTT and LDH assays. Primary murine cell cultures containing only astroglia cells originated from two brain regions, as well as mixed neurons and glia cells or microglia cells exclusively, were treated with anatase and rutile TiO2 nanoparticles at varying concentrations for 24 or 48 hours. Our results show that neither anatase nor rutile nanoparticles reduced viability in cell cultures containing a mixture of neurons and glial cells, independently of the applied concentration and treatment time. Rutile but not anatase form induced cell death in cortical astroglia cultures already at 24 hours of treatment above 10 {micro}g/mL, while hippocampus-derived glial cultures were much less sensitive to rutile. The rutile form also damaged microglia. These findings suggest that products containing rutile-form nano-titanium particles may pose a targeted risk to astroglia and microglial cells in the central nervous system.

neuroscience↗

bioRxiv2025

Chromosomal fusions and subsequent rearrangements shaped octopus genomes

Why some animal groups retain ancestral chromosomal complements while others change significantly is a fundamental question in evolutionary genomics. Few systems exist where accumulations of chromosomal changes can be studied in the context of morphological innovation. In coleoid cephalopods (octopus, squid, cuttlefish), an ancient coleoid chromosomal rearrangement event (ACCRE) has led to a substantial increase in the chromosome number and a new set of chromosomal homologies. Compared to typical molluscan or bilaterian genomes, ACCRE has enabled the origin of many novel regulatory regions in coleoid cephalopods. However, the discrepancies between extant octopodiform (octopus, [~]30 chromosomes) and decapodiform (squid and cuttlefish, [~]46 chromosomes) karyotypes and the direction of these evolutionary changes remain unexplained. Here we provide a draft genome assembly of the vampire squid Vampyroteuthis sp., the largest cephalopod genome sequenced to-date (over 10 gigabasepairs). Through syntenic comparisons, we infer that this basally branching octopodiform species shows partial retention of the chromosomal complement of Decapodiformes, indicating its more ancestral state and the derived nature of the octopod karyotype. Together with the analysis of a new chromosome-level assembly of the pelagic octopod Argonauta hians, we identified irreversible chromosomal fusion-with-mixing events followed by inter-chromosomal translocations in octopods. We show that this secondary reduction and mixing within octopod chromosomes has enabled the origin of a more entangled genomic configuration, shedding light onto the early evolutionary transitions within the clade. Our results offer broader insights into general patterns of chromosomal evolution following large-scale rearrangement events in animal genomes. Significance statementHow changes to the ancient animal synteny result in novel chromosomal homologies is difficult to dissect due to the lack of intermediate states. Here we report that the genome of Vampyroteuthis, one of the largest animal genomes sequenced to-date (over 11 gigabasepairs), despite its phylogenetic position within the octopodiform cephalopods, partially retains squid and cuttlefish chromosomal complement, reflecting an ancestral karyotypic state that existed at the time of divergence between these cephalopod lineages. Our findings reveal karyotype reductions through chromosomal fusions were followed by inter-chromosomal translocations in octopods, leading to a more specialized genomic and gene regulatory architecture. These data show how chromosomal fusions can act as drivers of further inter-chromosomal rearrangements in animal genomes.

genomics↗

bioRxiv2022

PADAPT 1.0 - the Pannonian Database of Plant Traits

We present PADAPT 1.0, the Pannonian Database of Plant Traits which relies on regional data sources and integrates existing data and new measurements on a wide range of traits and attributes of the plant species of the Pannonian Biogeographical Region and makes it freely accessible at www.padapt.eu. The current version covers the species of the region occurring in Hungary (cc. 90% of the regions flora) and consists of 126,337 records on 2745 taxa. There are 53 plant attributes in PADAPT 1.0 organised in six major groups: (i) Habitus and strategy, (ii) Reproduction, (iii) Kariology, (iv) Distribution and conservation, (v) Ecological indicator values, and (vi) Leaf traits. By including species of the eastern part of Europe not covered by other databases, PADAPT can facilitate studying the flora and vegetation of the eastern part of the continent. Data collection will continue in the future and the PADAPT team welcomes researchers interested in contributing with data. The main task before an updated version of the database is to include species of the Pannonian region not covered by the current version. In conclusion, although data coverage is far from complete, PADAPT meets the longstanding need for a regional database of the Pannonian flora.

ecology↗

bioRxiv2022

Rapid Identity and Quantity CQA Test for Multivalent mRNA Drug Product Formulations

The COVID-19 pandemic highlighted mRNA as a promising platform for vaccines and therapeutics. Many of the analytical tools used to characterize the critical quality attributes of mRNA are inherently singleplex and are not necessarily optimal from a labor and cost perspective. Here we demonstrate feasibility of a multiplexed platform (VaxArray) for efficient identity verification and concentration determination for both monovalent and multivalent mRNA formulations. A model system comprised of mRNA constructs for influenza hemagglutinin and neuraminidase was used to characterize the analytical performance metrics for a VaxArray mRNA assay. The assay presented herein had a time to result of less than 2 hours, required no PCR-based amplification nor extraction of mRNA from lipid nanoparticles, and exhibited high construct specificity that enabled application to the bivalent mixture. The sensitivity for influenza hemagglutinin and neuraminidase mRNA was sub-{micro}g/mL, which is vaccine-relevant, and the average accuracy (%recovery) and precision were 104%{+/-}2%and 9%{+/-}2%, respectively.

bioengineering↗

bioRxiv2022

Target-matched increased fidelity SpCas9 variants can edit any target without genome-wide off-target effects

Streptococcus pyogenes Cas9 (SpCas9) has been employed as a genome engineering tool with a promising potential within therapeutics. However, its off- target effects pose a major limitation for applications requiring high specificity. Approaches developed to date to mitigate this effect, including any of the increased fidelity (i.e., high-fidelity) SpCas9 variants, only provide efficient editing on a relatively small fraction of targets without detectable off-targets. Upon addressing this problem, we have revealed a rather unexpected cleavability ranking of target sequences, and a cleavage rule that governs the on-target and off-target cleavage of increased fidelity SpCas9 variants but not that of SpCas9-NG or xCas9. As a consequence of this rule, each target needs a matching-fidelity, optimal variant for efficient cleavage without detectable off-target effects. By exploiting this finding, we have developed an extended set of increased fidelity variants spanning across a wide range, with differences in fidelity small enough to comprise an optimal variant for any target, irrespective of its cleavability ranking. We have demonstrated efficient editing with maximum specificity even on those targets that have been challenged but failed in previous studies.

molecular biology↗

bioRxiv2021

Sand dropseed (Sporobolus cryptandrus) - A new pest in Eurasian sand areas?

For the effective control of an invasive species, gathering as much information as possible on its ecology, establishment and persistence in the subjected communities is of utmost importance. We aimed to review the current distribution and characteristics of Sporobolus cryptandrus (sand dropseed), an invasive C4 grass species of North American origin recently discovered in Hungary. We aimed to provide information on (i) its current distribution paying special attention to its invasion in Eurasia; (ii) the characteristics of the invaded habitats in Central Europe; (iii) seed bank formation and germination characteristics, crucial factors in early establishment; and (iv) the effects of its increasing cover on vegetation composition. Finally, we aimed to (v) point out further research directions that could enable us to understand the invasion success of this potential invasive species. Field surveys uncovered large stands of the species in Central and Eastern Hungary with most of the locations in the former, especially the Kiskunsag region. The species invaded disturbed stands of dry and open sand grasslands, closed dune slack grasslands and it also penetrates into natural open sand grasslands from neighbouring disturbed habitats. Increasing cover of Sporobolus cryptandrus caused a decline in species richness and abundance of subordinate species both in the vegetation and seed banks, but a low density of Sporobolus cryptandrus can even have a weak positive effect on these characteristics. Viable seeds of Sporobolus were detected from all soil layers (2.5 cm layers measured from the surface to 10 cm in depth), which indicates that the species is able to form a persistent seed bank (1,114 to 3,077 seeds/m2 with increasing scores towards higher abundance of the species in vegetation). Germination of Sporobolus cryptandrus was negatively affected by both litter cover and 1 cm deep soil burial. To sum up, Sporobolus cryptandrus can be considered as a transformer invasive species, whose spread forms a high risk for dry sand and steppe grasslands in Eurasia. We can conclude that for the effective suppression of the species it is necessary: (i) to clarify the origin of the detected populations; (ii) to assess its competitive ability including its potential allelopathic effects; (iii) to assess its seed bank formation potential in habitats with different abiotic conditions; and (iv) to assess the possibility of its suppression by natural enemies and management techniques such as mowing or livestock grazing.

ecology↗

bioRxiv2020

Anterior Nucleus of Thalamus Gates Progression of Mesial Temporal Seizures by Modulating Thalamocortical Synchrony

The anterior nucleus of the thalamus (ANT) mediates cortical-subcortical interactions between the limbic system and is hypothesized to facilitate the early organization of temporal lobe seizures. We set out to investigate the dynamic changes in synchronization parameters between the seizure onset zone (SOZ) and ANT during seizure stages (pre-onset to post-termination) in seven patients (n=26 seizures) with drug-resistant nonlesional temporal lobe epilepsy. Using local field potentials recorded directly from the limbic system and the ANT during stereoelectroencephalography, we confirm that the onset of mesial temporal lobe seizure is associated with increased thalamocortical network excitability and phase-amplitude coupling. The increase in thalamocortical phase synchronization preceded seizure onset, thereby suggesting that the early organization of temporal lobe seizures involves the integration of the ANT within the epileptic network. Towards seizure termination, there is a significant decrease in thalamic excitability, thalamocortical synchronization, and decoupling, thereby suggesting a breakdown in thalamocortical connectivity. A higher disease burden is significantly correlated with increased synchronization between the ANT and epileptic networks. Collectively, the results elucidate mechanistic insights and provide the temporal architecture of thalamocortical interactions that can be targeted in the rational designing of closed-loop seizure abortive interventions. HighlightsO_LIAnterior nucleus of thalamus is coactivated at the onset of temporal lobe seizures C_LIO_LIIncrease thalamocortical synchronization and excitability is observed at seizure onset C_LIO_LISeizure termination is characterized by a breakdown in thalamocortical connectivity C_LIO_LIIncreased seizure burden affects thalamocortical synchronization C_LI

neuroscience↗

bioRxiv2020

Non-linear Computation Between Neighboring Dendritic Hotspots in Rat CA1 Hippocampal Interneurons

Dendritic hotspots have been shown to play a determining role as local activity foci during sensory information coding and memory formation in cortical neurons in vivo. Here we aim to reveal the characteristics of co-activating more dendritic hotspots themselves within a dynamic time window. Using electrical stimulation and patterned two-photon uncaging for the coincident activation of two neighboring dendritic hotspots in rat hippocampal CA1 interneurons, the evoked local dendritic Ca2+ and the associated excitatory postsynaptic potentials (EPSPs) summed supralinearly. Between active hotspots, supralinearity was present in a relatively broad temporal ([~]10 ms) and spatial ([~]30 {micro}m) window, mediated by NMDA receptors. Though at larger inter-hotspot distances (>30 {micro}m) supralinear summation of EPSPs was replaced by sublinear integration, the summation of dendritic Ca2+ responses remained supralinear. The inter-hotspot integration represents a novel signal integration state, extending the interaction distance between dendritic inputs, and allowing long-range coincidence detection.

neuroscience↗

bioRxiv2020

Implantation technique, safety and complications of robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy

IntroductionDespite numerous imaging studies highlighting the importance of thalamus in surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei in patients with suspected temporal lobe epilepsy (TLE). MethodsAfter obtaining informed consent, 24 adults with drug-resistant suspected TLE undergoing Stereo-EEG evaluation were enrolled in this prospective study. The trajectory of one electrode planned for clinical sampling the operculo-insular cortex was modified to extend to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior thalamus (ANT) (N=13) and the medial group of thalamic nuclei (MED) (N=11), including mediodorsal (MD) and centromedian (CeM) were targeted. The post-implantation CT was co-registered to the pre-operative MRI, and Morels thalamic atlas was used to confirm the accuracy of implantation. ResultsTen out of 13 (77%) in the ANT group and 10 out of 11 patients (90%) in the medial group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical level entry site were noted in 20.8% of patients and they did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from the medial group at the entry point i.e., precentral gyrus in the former and postcentral gyrus in the latter. ConclusionsUsing judiciously planned robot-assisted SEEG, we demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes, or comprising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.

neuroscience↗

bioRxiv2020

Consumption rate and dietary choice of cattle in species-rich mesic grasslands

For the improvement and maintenance of the desirable ecological value of grasslands it is necessary to manage them in a way which maintains their structure and their long-term functioning. Extensive grazing plays a crucial role in the seasonal biomass removal, thereby it prevents litter accumulation and shrub encroachment. Defoliation and biomass removal are among the most important effects of grazing on the vegetation, while the sufficient quantity and quality of plant biomass is an important ecosystem service for animal husbandry. In order to maintain the long term functioning of pastures it is important to gather information about the amount of consumed biomass and the dietary choice of the grazers. Therefore, we studied the direct effects of grazing on species-rich meadow steppes in Central-Hungary and the underlying mechanisms of dietary choice of cattle using trait-based approach. We asked the following questions: (i) What are the direct effects of grazing on the main biomass fractions (litter, moss, forbs and graminoids)? (ii) Which traits distinguish the preferred and non-preferred vascular plant species? The studied pastures were divided into two adjacent units, which were managed differently in the study year: the grazed units were managed by grazing for three months before the sampling date, while the control units remained ungrazed until the sampling. We collected above-ground biomass samples, measured leaf traits and shoot nitrogen content of plants. The consumption of the litter and moss biomass was negligible, while the reduction of the live biomass of vascular plants was 65%. Grazing significantly decreased the flowering success of plants. Cattle consumed species characterized by high specific leaf area and high nitrogen content. Based on our results we emphasize that, in order to ensure the reproduction of most plant species in the long term, it is unfavourable to graze an area every year in the same period. Instead, it is recommended to use grazing in a mosaic spatial and temporal pattern. The livestock carrying capacity of an area and the long-term management of grasslands can be carefully planned based on biomass measurements and the nutritional value of plants, which is well indicated by some easily measurable plant properties such as specific leaf area and the nitrogen content of species.

ecology↗

bioRxiv2020

Germination response of invasive plants to soil burial depth and litter accumulation is species specific

QuestionsPlant invasions are considered among the biggest threats to biodiversity worldwide. In a full-factorial greenhouse experiment we analysed the effect of soil burial depth and litter cover on the germination of invasive plants. We hypothesised that (i) burial depth and litter cover affect the germination of the studied species, (ii) the effects of burial and litter cover interact with each other, and (iii) the effects are species-specific, but dependent on seed size. MethodsWe tested the germination and seedling growth of 11 herbaceous invasive species in a full-factorial experiment using four levels of seed burial depths and litter cover. We analysed the effect of burial, litter cover, and their interactions on germination, seedling length and biomass across species and at the species level. ResultsSoil burial depth and litter cover had a significant effect on the germination of the studied species, but there were considerable differences between species. We observed a general trend of species with bigger seeds being not or less seriously affected by soil burial and litter cover than smaller-seeded species. Correlations between seed weight and effect sizes mostly confirmed this general trend, but not in the case of soil burial. ConclusionsOur findings confirmed that seed size is a major driver of species response to litter cover and to the combined effects of litter cover and soil burial, but there is no general trend regarding the response to soil burial depth. Despite its very small seeds the germination of Cynodon dactylon was not affected by soil burial. The germination of Ambrosia artemisiifolia was hampered by both soil burial and litter cover despite its relatively large seeds. Thus, specific information on species response to burial depth and litter accumulation is crucial when planning management or restoration in areas threatened by plant invasions.

ecology↗

bioRxiv2019

Mapping short-latency cortical responses to electrical stimulation of thalamic motor nuclei by increasing sampling rate - a technical report

Direct electrical stimulation (DES) of the cortex is a clinically indispensable brain mapping technique that provides reliable information about the distribution of eloquent cortex and its connectivity to the white matter bundles. Here we present a technical report on mapping the short latency cortical responses to stimulation of the ventral anterior nucleus of human thalamus. Reliable downstream responses were noted in the regions connected to the ventral anterior nucleus i.e. superior and inferior frontal gyri, supplementary motor area and limbic substructures (cingulate gyrus and hippocampus).

neuroscience↗

bioRxiv2019

Ictal recruitment of anterior nucleus of thalamus in human focal epilepsy

The thalamic nuclei play diverse roles in the initiation, propagation, and termination of temporal lobe seizures. The role of the anterior nucleus of the thalamus (ANT) - a node that is integral to the limbic network is unclear. The objective of this study was to characterize temporal and - spectral patterns of ANT ictal recruitment in drug-resistant temporal lobe epilepsy (TLE). We hypothesized that seizures localized to the temporolimbic network are likely to recruit ANT, and the odds of recruitment were higher in seizures that had altered consciousness. Ten patients undergoing stereo-electroencephalography (SEEG) were recruited prospectively to record field potentials from the ANT. Using epileptogenicity index and line length, we computed the number of seizures that recruited the ANT (recruitment ratio), the recruitment latencies between the ANT and the epileptogenic zone (EZ), and latency of ANT recruitment to clinical manifestation for seventy-nine seizures. We observed that seizures localized to mesial temporal subregions (hippocampus, amygdala, anterior cingulate) have a higher predilection for ANT recruitment, and the recruitment was faster (ranged 5-12 secs) and preceded clinical onset for seizures that impaired consciousness. Seizures that recruited ANT lasted significantly longer (t=1.795, p=0.005). Recruitment latency was inversely correlated to seizure duration (r=-0.78, p=0.004). Electrical stimulation of the EZ induced seizures, in which early recruitment of ANT was confirmed. Stimulation of ANT did not induce a seizure. Finally, we tested the hypothesis that spectral and entropy-based features extracted from thalamic field potentials can distinguish its state of ictal recruitment from other interictal states (including awake, sleep). For this, we employed classification machine learning that discriminated thalamic ictal state from other interictal states with high accuracy (92.8%) and precision (93.1%). Among the features, the emergence of the theta rhythm (4-8 Hz) maximally discriminated the endogenous ictal state from other interictal states of vigilance. These results prompt a mechanistic role for the ANT in the early organization and sustaining of seizures, and the possibility to serve as a target for therapeutic closed-loop stimulation in TLE.

neuroscience↗

bioRxiv2019

A morphological analysis of activity-dependent myelination and myelin injury in transitional oligodendrocytes

Neuronal activity is established as a driver of oligodendrocyte (OL) differentiation and myelination. The concept of activity-dependent myelin plasticity, and its role in cognition and disease, is gaining support. Methods capable of resolving changes in the morphology of individual myelinating OL would advance our understanding of myelin plasticity and injury, thus we adapted a labelling approach involving Semliki Forest Virus (SFV) vectors to resolve and quantify the 3-D structure of OL processes and internodes in cerebellar slice cultures. We first demonstrate the utility of the approach by studying changes in OL morphology after complement-mediated injury. SFV vectors injected into cerebellar white matter labelled transitional OL (TOL), whose characteristic mixture of myelinating and non-myelinating processes exhibited significant degeneration after complement injury. The method was also capable of resolving finer changes in morphology related to neuronal activity. Prolonged suppression of neuronal activity, which reduced myelination, increased the number of TOL processes, while decreasing both the length of putative internodes, and the proportion of myelinating terminal branches. Overall this approach provides novel information on the morphology of TOL, and new opportunities to study the response of OL to conditions that alter circuit function or induce demyelination.

neuroscience↗

bioRxiv2019

Early Ictal Recruitment of Midline Thalamus in Mesial Temporal Lobe Epilepsy

The causal role of midline thalamus in the initiation and early organization of mesial temporal lobe seizures is studied. Three patients undergoing stereoelectroencephalography were enrolled for the placement of an additional depth electrode targeting the midline thalamus. The midline thalamus was recruited in all three patients at varying points of seizure initiation (0-13 seconds) and early propagation (9-60 seconds). Stimulation of either thalamus or hippocampus induced similar habitual seizures. Seizure-induced in the hippocampus rapidly recruited the thalamus. Evoked potentials demonstrated stronger connectivity from the hippocampus to the thalamus than in the opposite direction. The midline thalamus can be within the seizure initiation and symptomatogenic circuits.

neuroscience↗

bioRxiv2018

Influence of mutagenic versus non-mutagenic pre-operative chemotherapy on the immune infiltration of breast cancer

BackgroundChemotherapeutic agents are often mutagenic. Induction of mutation associated neo-epitopes is one of the mechanisms by which chemotherapy is thought to increase the number of tumor-infiltrating lymphocytes, but the clinical relevance of this triggered immune response is not known.\n\nWe decided to investigate, whether treatment with various chemotherapeutic agents with significantly different mutagenic capacity induce a significantly different number of stromal tumor-infiltrating lymphocytes (StrTIL) in the clinical setting.\n\nMethods112 breast carcinoma cases treated with pre-operative chemotherapy were selected for the study. According to chemotherapy regimen 28/112 patients received platinum-based, 42/112 cyclophosphamide-based and 42/112 anthracycline-based chemotherapy. The percentage of stromal tumor-infiltrating lymphocytes (StrTIL) was evaluated on hematoxylineosin stained slides of pre-treatment core biopsy (pre-StrTIL) and post-treatment surgical tumor samples (post-StrTIL), according to the most recent recommendation of International TILs Working Group. In survival analyses, TIL changes ({Delta}StrTIL) were calculated from the difference between post-StrTIL and pre-StrTIL.\n\nResultsOf the 112 cases, 58.0% (n=65) were hormone receptor (HR) positive and 42.0% (n=47) were HR negative. There was a trend of higher post-StrTIL compared to pre-StrTIL (median 6.25% vs. 3.00%; p<0.001). When analyzing the pre-StrTIL and post-StrTIL among the three treatment groups, we experienced significant StrTIL increase independently of the treatment applied. Based on the results of survival analyses both post-StrTIL and {Delta}StrTIL was found to be independent prognostic factor in HR negative cases. Each 1% increase in post-StrTIL reduced the hazard of distant metastases development by 2.6% (hazard ratio: 0.974; CI: 0.948-1.000; p=0.05) and for each 1% {Delta}StrTIL increment, the risk of distant metastases was reduced by 4.3% (hazard ratio: 0.957; CI: 0.932-0.983; p=0.001). The prognostic role of StrTIL in HR positive cases could not be proven.\n\nConclusionsStrTIL expression might be stimulated by highly (platinum), moderately (cyclophosphamide) and marginally (taxane, anthracycline) mutagenic chemotherapeutic agents. Increase in StrTIL in residual cancer compared to pre-treatment tumor tissue is associated with improved distant metastasis-free survival in cases with HR negative breast carcinoma.

cancer biology↗

bioRxiv2018

Breast cancer brain metastases show increased levels of genomic aberration based homologous recombination deficiency scores relative to their corresponding primary tumors

Due to its mechanism of action, PARP inhibitor therapy is expected to benefit mainly tumor cases with homologous recombination deficiency (HRD). Various measures of genomic scarring based HRD scores were developed as a companion diagnostic in order to correlate it with PARP inhibitor sensitivity. We compared a variety of HRD scores in primary tumors and their corresponding brain metastases and found a significant increase in this measure in brain metastases for all measures of HRD that were tested. This discrepancy warrants further investigation to assess whether this observation is common to other metastatic sites, and potentially a significant adjustment of strategy in the application of HRD measures in clinical trials for the prioritization of patients for PARP inhibitor therapy.\n\nKey messageWe quantified homologous recombination deficiency (HRD) in paired primary breast cancer and brain metastases samples based on a previously published data set. We showed that HRD significantly increases in the brain metastases relative to its paired primary tumor. An independent validation was also performed on another set of primary breast cancer and brain metastasis pairs using the \"my choice\" HRD score in collaboration with Myriad Genetics.\n\nThese confirmatory results suggest that brain metastases of breast cancer tend to have significantly higher HRD scores, which would prioritize those patients for PARP inhibitor therapy with those agents that cross the blood brain barrier such as veliparib and niraparib.

cancer biology↗