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  • Journal article
    Celsa C, Pressiani T, Nishida N, Mohamad Chamseddine S, Arvind A, Li M, Fortuny M, Ben Khaled N, Iavarone M, Toyoda H, Giovanni Rapposelli I, Casadei-Gardini A, Vivaldi C, Ulahannan S, Andanamala H, Scheiner B, Pinter M, Orlandi E, Fulgenzi CAM, Manfredi GF, Lombardi P, DAlessio A, Stefanini B, Villani R, Romana Ponziani F, Stella L, Carminati O, Dalia Ricci A, Gonzalez M, Sparacino A, Di Maria G, Vaccaro M, Cabibbo G, Cammà C, Reig M, Kelley RK, Singal AG, Kaseb AO, Kudo M, Rimassa L, Pinato Det al., 2026,

    Reproducible safety and efficacy of durvalumab with or without tremelimumab for hepatocellular carcinoma in clinical practice: Results of the DT-real study

    , JHEP Reports, Vol: 8, ISSN: 2589-5559

    Background & AimsDurvalumab plus tremelimumab (STRIDE) has emerged as a first-line systemic treatment option for unresectable hepatocellular carcinoma (HCC). This international multicentre study aimed to evaluate the efficacy and tolerability of STRIDE or durvalumab monotherapy in routine clinical practice, comparing outcomes between patients within and outside key eligibility criteria for the HIMALAYA trial.MethodsFrom a database of 1,423 patients with advanced/unresectable HCC treated with immunotherapy across 35 centres, we analysed 233 patients receiving STRIDE or durvalumab monotherapy. Patients were categorized as HIMALAYA-IN or HIMALAYA-OUT based on key trial eligibility criteria (no prior systemic therapy, ECOG-PS 0–1, Child-Pugh class A, no Vp4 thrombosis). Baseline characteristics were assessed for overall survival (OS) and hepatic decompensation using a multivariable Cox model and competing-risk analysis, respectively. Objective response rates and treatment-related adverse events were recorded.ResultsOf the 233 patients, 123 (53%) were HIMALAYA-IN and 110 (47%) were HIMALAYA-OUT. STRIDE was given in 95% of HIMALAYA-IN patients. After median follow-up of 6.0 months, median OS was 20.4 months (95% CI 11.7-NR) in the overall population. HIMALAYA-IN patients achieved significantly longer OS than HIMALAYA-OUT patients (23.0 vs. 12.2 months; hazard ratio 0.61; 95% CI 0.39-0.96; p = 0.03). Macrovascular invasion and hepatic decompensation were independent negative prognostic factors in the whole cohort. Hepatic decompensation occurred in 10.5% of patients within 12 months from treatment start. Objective response rate was 23.7% and 17.8% of HIMALAYA-IN and -OUT patients, respectively. Patients achieving disease control (whole cohort: 59.4%) demonstrated 24-month OS of 58.2% in HIMALAYA-IN and 44.8% in HIMALAYA-OUT groups. Grade 3-4 treatment-related adverse events occurred in 16.3% of patients.ConclusionsSTRIDE shows reproducible effectiveness and an ac
  • Journal article
    Habiburrahman M, Masrour N, Patel N, Piskorz AM, Brown R, Brenton JD, Mcneish IA, Flanagan JMet al., 2026,

    Clinical validation of a DNA methylation biomarker associated with overall survival of relapsed ovarian cancer patients

    , International Journal of Cancer, Vol: 158, Pages: 1821-1835, ISSN: 0020-7136

    Approximately 70% of ovarian cancer (OC) patients relapse after chemotherapy, underscoring the need to assess survival before second-line treatment. We previously identified PLAT-M8, an 8-CpG blood-based methylation signature linked to chemoresistance. This study validates its correlation with clinicopathological features and treatment profiles in additional cohorts. Extracted DNA from whole blood was provided from the BriTROC-1 (n = 47) and OV04 cohorts (n = 57) upon the first relapse. Additional samples from Hammersmith Hospital (n = 100) were collected during first-line chemotherapy (Cycles 3–4 and 6). Bisulphite pyrosequencing was used to quantify DNA methylation at the previously identified 8 CpG sites. The methylation data obtained were combined with previous data from ScoTROC-1D and 1V (n = 141) and OCTIPS (n = 46). Cox regression was used to assess OS after relapse concerning clinicopathological characteristics. The DNA methylation Class (Class 1 vs. 2) was determined by consensus clustering. As for results, blood DNA methylation at relapse correlates with clinical outcomes, but it has no impact during first-line treatment. Class 1 is linked to shorter survival (summary OS: HR 2.50, 1.64–3.79) and poorer prognosis on carboplatin monotherapy (OS: aHR 9.69, 95% CI: 2.38–39.47). It is associated with older (>75 years), advanced-stage, platinum-resistant patients, residual disease, and shorter PFS. In contrast, Class 2 is linked to platinum sensitivity, higher complete response rates (RECIST), and better prognosis but shows no correlation with CA-125. These findings highlight PLAT-M8's potential in guiding second-line chemotherapy decisions. The PLAT-M8 methylation biomarker is associated with survival in relapsed OC patients and may potentially predict their response to second-line platinum treatment.
  • Journal article
    Pinato DJ, 2026,

    Neoantigen-based vaccination unlocks precision immunotherapy in fibrolamellar carcinoma.

    , J Hepatol, Vol: 84, Pages: 843-845
  • Journal article
    Vieito M, Fontana E, Han CH, Castanon E, Pinato DJ, Bechter O, Eefsen RL, Moreno I, Prenen H, Dummer R, Plummer R, Schnetzler G, Kornacker M, Pettazzoni P, Renner F, About M, Serrano-Serrano ML, Godfried Sie C, Keelara A, Roller A, Dejardin D, Cinato E, Fakolade T, Guarin E, Flinn N, Kratochwil NA, Keshelava Net al., 2026,

    Phase I Study of Mosperafenib, a Novel Paradox Breaker B-Raf Proto-Oncogene Serine/Threonine Kinase (BRAF) Inhibitor, in Patients With <i>BRAF</i> V600-Mutant Solid Tumors

    , Journal of Clinical Oncology, ISSN: 0732-183X

    <jats:sec> <jats:title>PURPOSE</jats:title> <jats:p> <jats:italic toggle="yes">BRAF</jats:italic> V600 mutations are tumor-agnostic oncogenic drivers whose targeted inhibition is challenged by therapeutic resistance. Mosperafenib is a novel paradox breaker and brain-penetrant BRAF inhibitor (BRAFi), tested in this study for safety, maximum tolerated dose (MTD), pharmacokinetics (PK), and preliminary clinical activity. </jats:p> </jats:sec> <jats:sec> <jats:title>PATIENTS AND METHODS</jats:title> <jats:p> This phase Ia/b study was conducted in patients with advanced solid tumors harboring a <jats:italic toggle="yes">BRAF</jats:italic> V600 mutation (ISRCTN13713551). The modified continuous reassessment method guided dose escalation of mosperafenib, which was given orally up to 3,600 mg once daily in 28-day cycles. The primary objective was to estimate the MTD and/or recommended phase II dose(s). </jats:p> </jats:sec> <jats:sec> <jats:title>RESULTS</jats:title> <jats:p>Eighty patients (60% BRAFi-exposed)—63 with colorectal cancer (CRC), 13 with melanoma, and 4 with other solid tumors—received ≥1 dose of mosperafenib as a single agent for a median of 3.7 months (range, 0.2-28.6). Two dose-limiting grade 3 toxicities of rash and rash maculopapular were reported. MTD was not reached. Grade 3 to 4 treatment-related adverse events (TRAEs) occurred in 13 patients (16.3%); no grade 5 TRAEs events were reported. Two patients (2.5%) discontinued study treatment due to TRAEs. There were no reports of palmar
  • Journal article
    Cunnington A, 2026,

    Predicting trajectories of illness using RNA velocity of whole blood

    , Nature Communications, ISSN: 2041-1723
  • Journal article
    Dunican C, Wilson C, Coote D, Paterson S, Noursadeghi M, Moseki R, Stek C, Wilkinson R, Agueman P, Beudeker C, Biesbroek C, von Both U, Brengel-Pesce K, Carrol E, Coin L, D'Souza G, De T, Emonts M, Fidler K, Fink C, Van Der Flier M, Georgaki I, Kolberg L, Kolnik M, Kuijpers T, Martinon-Torres F, Mommert-Tripon M, Nichols S, Paulus S, Pokorn M, Pollard A, Rivero-Calle I, Rudzate A, Schlapbach L, Schweintzger N, Shen C-F, Shrestha S, Tan C, Tsolia M, Usuf E, van der Velden F, Vermont C, Voice M, Yeung S, Zavadska D, Zenz W, Wright V, Levin M, Herberg J, Lai R, Meintjes G, Chiu C, Barahona M, Kaforou M, Cunnington Aet al., 2026,

    Predicting trajectories of illness using RNA velocity of whole blood

    , Nature Communications, ISSN: 2041-1723
  • Journal article
    Christou N, Fitikides N, Yan X, Vadukul D, Ying L, Vilar Compte R, Aprile Fet al., 2026,

    Cobalt(III) complexes as promoters of amyloid-β fibril destabilization

    , ChemMedChem, ISSN: 1860-7179

    Alzheimer’s disease is linked to the formation of pathological aggregates of the amyloid-β peptide in the brain. The N-terminus of amyloid-β plays an important role in modulating aggregation through metal- ion binding. It also remains solvent-accessible in both the monomers and the amyloid fibrils. This observation inspired us to synthesize cobalt(III) metal complexes featuring functionalized aromatic ligands, aimed at targeting amyloid-β N-terminus to influence aggregation. Through chemical kinetic analysis, we found that our cobalt(III) complexes modulate both primary and secondary nucleation pathways. Furthermore, total internal reflection fluorescence microscopy demonstrated that the compounds could disrupt preformed amyloid fibrils. Under physiologically relevant oxidative conditions, inhibition of fibril formation was reduced, whereas fibril disassembly remained largely preserved. This indicates that oxidation selectively impairs the aggregation-inhibiting mechanism without substantially affecting fibril disassembly. These findings suggest that inhibition of aggregation depends on interactions with protein species, e.g., monomers and oligomers, whose conformations are likely altered in an oxidative environment, thereby diminishing compound efficacy. In contrast, the structural features of mature fibrils formed under oxidative conditions remain susceptible to compound-induced destabilization. The preserved disaggregation activity of the cobalt(III) complexes under oxidative conditions resembling those associated with late-stage Alzheimer’s disease supports further investigation of their therapeutic potential.
  • Journal article
    Agnorelli C, Peill J, Sawicka G, Kurtin D, Shatalina E, Ahmad K, Wall MB, Rua C, Godfrey K, Ertl N, Searle G, Zhou K, Osugo M, Weiss B, Greenway KT, Fagiolini A, Carhart-Harris R, Matthews PM, Rabiner EA, Nutt D, Erritzoe Det al., 2026,

    Detecting neuroplastic effects induced by ketamine in healthy human subjects: A multimodal approach.

    , J Cereb Blood Flow Metab

    We investigated ketamine's neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1-8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven male participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (glutamate and GABA) and resting-state fMRI (intrinsic brain activity, functional connectivity), before and after ketamine. While group-level analyses showed no significant increases in PET synaptic markers, ketamine administration resulted in significantly elevated glutamate levels within the anterior cingulate cortex (ACC). Functional connectivity analyses revealed reduced coupling between the ACC and the dorsolateral prefrontal cortex (dlPFC) and increased coupling between the ACC and the amygdala in the days following ketamine administration. Our multimodal analysis revealed that participants showing an increase in [11C]-UCBJ volume distribution (VT), a putative index of synaptic plasticity, showed a correlated reduction in intrinsic activity within regions belonging to the default mode network (DMN). By linking molecular, cellular and network-level changes, our results point to the DMN as a central hub where ketamine may reshape brain hierarchies in the long term, providing new directions for understanding its therapeutic mechanisms and developing targeted treatments.
  • Journal article
    Moore Jr J, 2026,

    Excessive shear rate, not shear stress, influences cell mechanical damage in small-bore needle injections

    , Journal of Biomechanical Engineering, ISSN: 0148-0731

    Purpose: Cell therapies and 3D bioprinting often require suspended cells to be delivered through needles of 20-gauge and smaller. This often damages cells, affecting their short and long-term viability. Most researchers have attributed this to excessive viscous stresses encountered entering or within the needle, but the experimental evidence contradicts that, as higher viscosity suspension fluids generally yield higher cell viabilities when injected at the same flow rate. We therefore sought to determine the most relevant fluid flow parameter influencing cell mechanical damage.Methods: A combination of reprocessing published results and cell injection experiments were conducted. Human umbilical vein endothelial cells were suspended in Newtonian fluids of varying viscosities and injected through 30-gauge syringe needles in experiments that controlled for either shear stress or shear rate (a kinematic quantity expressing relative velocity of adjacent fluid layers).Results: Based on evidence from injection experiments using a variety of fluids, it is shown that increasing shear rate better explains reductions in cell viability than increasing shear stress. Conclusion: Knowledge that shear rate is a more relevant fluid mechanical parameter governing mechanical damage provides a rational basis for designing injection protocols (injectors and suspension fluid rheological properties) to maximize cell viability.
  • Journal article
    Rasmussen AB, Swann OC, Brown JC, Sukhova K, Liu N, Brown MD, Levitt CJL, Martin-Sancho L, Sheppard CM, Barclay WSet al., 2026,

    Influenza A virus polymerase co-opts distinct sets of host proteins for RNA transcription or replication.

    , Cell Chem Biol, Vol: 33, Pages: 338-352.e7

    The influenza A virus polymerase, consisting of a heterotrimer of three viral proteins, carries out both transcription and replication of the viral RNA genome. These distinct activities are regulated by viral proteins and various co-opted host cell proteins, which serve as targets for the development of novel antiviral interventions. However, little is known about which host proteins direct transcription versus replication. In this report, we performed a differential interactome screen to identify host proteins co-opted downstream or upstream of primary transcription, some of which may be transcription- or replication-specific factors. We found that distinct sets of host proteins interact with the influenza polymerase as it carries out the different activities. We functionally characterized HMGB2 and RUVBL2 as replication cofactors and RPAP2 as a transcription cofactor. Our data demonstrate that comparative proteomics can be used as a targeted approach to uncover virus-host interactions that regulate specific stages of the viral life cycle.

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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