Conventional receptor-targeted fluorescent probes have shown promise in tumor imaging, yet achieving a high tumor-to-normal (T/N) tissue ratio in vivo remains challenging due to limited biomarker density on tumor cell membranes. Here, we present an in situ assembly strategy of bioorthogonal-functionalized chimeric artificial receptors (BCARs) that locally constructs BCARs on tumor surfaces, which amplify fluorescence signals and enable high-contrast imaging. Rapid, selective membrane engineering under physiological conditions increases effective receptor density, enhancing fluorophore binding and tumor visualization. Mechanistic studies reveal that BCARs exhibit exceptional membrane retention and spatial precision, sustaining signal amplification in heterogeneous tumor microenvironments. In air-pouch and orthotopic bladder cancer models, BCARs notably improve the T/N imaging ratio and tumor boundary delineation. Translational validation with surgical specimens from 14 patients with bladder cancer confirms clinical feasibility. This work establishes a versatile platform for on-site receptor reprogramming and signal amplification, offering a powerful tool for high-contrast tumor margin detection.

Therapeutic resistance remains a major challenge in cancer treatment, driven by compensatory signaling and stress response pathways that sustain tumor survival. Topoisomerase IIβ-binding protein 1 (TopBP1), a multifunctional scaffold protein with nine BRCT domains, integrates replication stress signaling with oncogenic networks and is frequently overexpressed in aggressive cancers. Its BRCT7/8 domains mediate critical interactions with E2F1, mutant p53, MIZ1, PLK1, and CIP2A, making TopBP1-BRCT7/8 an attractive therapeutic target. Using docking-guided screening and structure-activity relationship-driven optimization, we developed CS18 as a potent and selective BRCT7/8 inhibitor that disrupts oncogenic TopBP1 complexes without interfering with DNA replication. CS18 suppresses MYC transcriptional programs, restores E2F1-mediated apoptosis, and induces mitotic catastrophe. It exhibits broad-spectrum anticancer activity and synergizes with poly(ADP-ribose) polymerase (PARP) inhibitors in multiple cancer types and enhances osimertinib sensitivity in EGFR-mutated non-small cell lung cancer (NSCLC) cells. CS18 demonstrates efficacy in patient-derived breast cancer xenografts and overcomes osimertinib resistance in refractory NSCLC in vivo. These findings establish CS18 as a chemically distinct TopBP1 inhibitor with translational potential to overcome therapeutic resistance and advance precision oncology.

Background and objectives Drug resistance and off-target toxicity remain major challenges in cancer therapy. Due to rapid proliferating nature of malignant cells, microtubule-targeting agents (MTAs) are widely used for chemotherapy, although their clinical efficacy is often limited by drug resistance and adverse effects. Objective of this study was to identify a novel therapeutic agent capable of selectively targeting microtubules in cancer cells while minimising toxicity to normal cells. Present study evaluates the chemotherapeutic potential of Vibrio cholerae haemagglutinin protease (HAP) as a novel MTA for gastric and colon cancers by investigating its role in microtubule degradation and apoptosis induction. Methods Effects of HAP were evaluated in human gastric and colon cancer cells using cellular and molecular assays. Time-dependent live-cell imaging was employed to assess HAP internalisation and co-localisation within intracellular organelles. Explant cultures derived from human tumour tissues were used to replicate the tumour microenvironment and validate therapeutic responses. Results HAP treatment activated protease-activated receptor 1 (PAR1), which is overexpressed in malignant cells, leading to an increase in intracellular reactive oxygen species (ROS) and facilitated HAP internalisation. Once internalised, HAP induced microtubule degradation through four mechanisms: ROS-mediated degradation of MAP2 and tau, destabilising microtubule network; enhancing tubulin-PARKIN interaction, enabling microtubule ubiquitination; and activation of lysosomal and proteasomal pathways to degrade microtubules. Collectively these events triggered apoptotic cascades in cancer cells and explant tissues, while normal healthy cells remained unaffected. Interpretation and conclusions HAP demonstrates strong potential as a selective anticancer therapeutic by inducing microtubule degradation and apoptosis without compromising viability of normal cells.

Massage is widely used in cancer survivors. However, formal assessment of potential harms is lacking. The aim of this study is to assess harms related to massage.

This systematic review and meta-analysis included studies that compared massage with control conditions, in people with- and/or receiving treatment for cancer. The primary outcome was adverse events. Ten databases and trials registries were searched up to 22 October 2024. Quality of adverse events reporting was assessed as adherence to the CONSORT statement extension for reporting of harms. Studies reporting on adverse events were assessed for risk of bias using the PEDro scale (randomized controlled/ cross-over trials) and ROBINS-I (quasi-experimental and cohort) and were eligible for meta-analysis (random-effect). The study was registered at PROSPERO (CRD42023352993).

Sixty-three intervention studies were included, of which 53% (n = 34 studies) did not report on adverse events. Twenty-nine studies (n = 2699) reported on adverse events explicity and/or as study discontinuation. Of these, no studies assessed deep massage, with most interventions using light massage. Meta-analyses indicated no evidence of a higher risk of adverse events related to massage compared to usual care/attention control. Three cohort studies (n = 1406) were included, two of which (both with critical risk of bias) found significant associations between massage over tumor site and negative survival outcomes, in patients with osteosarcoma. Overall, the quality of adverse events reporting was poor, and certainty of evidence considered very low.

Results indicate that light to moderate intensity massage in people living with- and/or receiving treatment for cancer can be performed without increased risk of harms. Contraindications for massage should be applied as per the general population. Due to uncertainty as to whether massage over tumor in osteosarcoma constitutes an increased risk of negative survival outcomes, massage directly on tumor is discouraged, though definitive evidence is lacking.

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent form of non-Hodgkin lymphoma, exhibiting significant molecular and clinical heterogeneity. Advances in classification integrating phenotypic, genetic, and transcriptomic features have improved diagnosis and prognosis. However, a comprehensive and integrated molecular characterization of DLBCL cell lines is still lacking, which limits their optimal use as reliable experimental models. We employed fluorescence in situ hybridization, immunohistochemistry, and targeted DNA and RNA sequencing to identify genetic subtypes and determine the cell of origin, providing a comprehensive characterization of 29 DLBCL cell lines through the integration of phenotypic, genomic, and transcriptomic data. Principal component analysis, gene set enrichment analysis (GSEA), differential expression profiling, and regulon analysis enabled us to dissect molecular heterogeneity. We achieved high concordance in genetic subtype assignment using multiple classification algorithms (2-S, LymphGen, and DLBclass). The DHIT/DZ signature and transcriptional profiling further revealed additional molecular complexity. Some DLBCL-NOS cases exhibited high-grade features, suggesting that gene expression signatures may capture biological aggressiveness better than cytogenetic methods. GSEA confirmed the relevance of signaling pathways across DLBCL subtypes, and regulatory network analysis identified specific transcription-factor activities that support these pathways. MCD cell lines showed increased NF-κB and STAT signaling, while EZB/MYC+ cell lines demonstrated increased proliferation and cell cycle regulation, along with decreased NF-κB/STAT activity. Our study offers a detailed molecular overview of DLBCL cell lines, underscoring their relevance for mechanistic and therapeutic research. The data highlights how integrating genetic and transcriptomic analyses can refine disease classification and guide personalized therapy strategies.

The aim of this retrospective study is to analyze the outcome and survival of patients with well-differentiated metastatic neuroendocrine neoplasm (NEN) treated with peptide receptor radionuclide therapy (PRRT).

The treatment was applied to 32 subjects, 18 men and 14 women, aged 39-79 years (median 65 years). The dominant grade of the tumor according to the Ki-67 index was G2 (75%) compared to G1 (25%). The average number of three-day protocol PRRT cycles was 4 (1.00-9.00). Lutetium-177- DOTA⁰,Tyr³,Thr⁸-octreotide (¹⁷⁷Lu-DOTA-TATE) was used in 22 (69%), both ¹⁷⁷Lu-DOTA-TATE and yttrium-90-DOTA⁰,Tyr³-octreotide (⁹⁰Y-DOTA-TOC) in 8 (25%), and ⁹⁰Y-DOTA-TOC in 2 (6%) patients. No adverse effects of PRRT were recorded excerpt one patient who has died soon after the first therapy due to ileus after surgery.

Response to PRRT according to response evaluation criteria in solid tumors (RECIST) 1.1. criteria showed that 9 (28%) patients had disease progression, 16 (50%) had stable disease, and 7 (22%) had partial remission. Significantly shorter time until progression or death of 18 months was detected for patients with disease progression than for other groups with stable disease (34.5 months, P<0.02) and partial remission (35 months, P<0.05). However, the values obtained for overall survival were not significantly different between the studied groups being 33 months in subjects with disease progression, and 34.5 and 35 months in groups with stable disease and partial remission, respectively. In 6 subjects, an asymptomatic low hemoglobin level was detected that did not require intervention (Grade1). In 2 subjects, nephrotoxicity occurred with glomerular filtration rate (GFR) values below 30mL/min/1.73m² (Grade3).

It can be concluded that PRRT according to a three-day nephroprotection protocol is a reliable and safe method of treatment for advanced NEN. Longer time to disease progression and overall survival in most patients underline the great potential of this treatment method in patients with advanced NEN.

SCF (Skp1-Cullin1-Fbox protein) is a multi-subunit RING-type E3 ligase and plays critical roles in various pivotal physiological and pathological processes by mediating the ubiquitination and degradation of key proteins. F-box proteins directly bind substrates, thereby determining their specificity, stability, and function. However, the regulatory mechanisms of FBXO21 degradation in human cancers remain largely elusive. In this study, we demonstrated that Neddylation-ROC1 E3 ligase regulates the protein level of FBXO21. Mechanistic studies revealed that Neddylation-ROC1 targeted FBXO21 for ubiquitination and degradation. Moreover, we found that FBXO21 depletion increased p53 protein stability by delaying its degradation, followed by increasing the transcriptional level of p21. Taken together, our findings reveal a previously unrecognized mechanism by which FBXO21 is regulated by Neddylation modification and regulates the p53-p21 signaling pathway.

This case report and literature review of previously published cases describe the rare complication of cerebral aspergillosis in paediatric neuro-oncology patients. A boy in early childhood with high-risk medulloblastoma developed recurrent episodes of febrile neutropenia, persistent headache and cerebrospinal fluid (CSF) pleocytosis following surgical resection and two courses of intensive chemotherapy. Despite broad-spectrum antibiotic therapy, the fever remained unresolved. He subsequently developed worsening headache along with ongoing CSF pleocytosis, raising suspicion of meningitis. Blood and cerebrospinal cultures were negative, and later, cerebral MRI revealed multiple ischaemic lesions and raised suspicion of large-vessel vasculitis with arterial occlusions. Regardless of adding methylprednisolone and amphotericin to the broad-spectrum antibiotic treatment, the boy developed hemiparesis, coma and seizures preceding death. Autopsy findings revealed cerebral aspergillosis and infiltration of inflammatory cells along the blood vessels.

Obstructive Sleep Apnoea (OSA) is a common, yet underdiagnosed disorder, with significant health implications. Continuous positive airway pressure (CPAP) remains the reference standard and first-line therapy. However, successful CPAP usage is influenced by factors such as access, cost, tolerance, patient education, early troubleshooting, and long-term adherence, all of which can be challenging and resource-demanding. Adding therapeutic options to the armamentarium is therefore welcome. There is a need for clinicians to be abreast of all the available therapeutic options for treatment of OSA.

We conducted an extensive literature review of the published studies that were conducted using non-CPAP pharmacotherapeutic modalities for OSA.

This narrative review summarises the current landscape of OSA pharmacotherapy, focusing on mechanisms of action, clinical trial evidence, and endotype-based selection strategies. Emerging therapies such as the atomoxetine-oxybutynin combination and topiramate show promise in reducing severity of OSA, and improving sleep quality. GLP-1 receptor agonists like liraglutide and tirzepatide offer benefits beyond reducing the severity of OSA. Other agents such as sulthiame, solriamfetol, and pitolisant have also demonstrated efficacy. Wake-promoting agents like modafinil and armodafinil target the commonest symptom of OSA, sleepiness.

This review provides a practical, endotype-aligned summary of pharmacologic options for the management of OSA.

Objective: To explore the clinical characteristics, efficacy and safety of different therapeutic regimens in patients with anti-MDA5 antibody positive dermatomyositis (anti-MDA5⁺DM) stratified by disease risk, and to analyze the influencing factors for prognosis. Methods: This was a retrospective cross-sectional study. Clinical data of 82 patients with anti-MDA5⁺DM admitted to the First Affiliated Hospital of Guangxi Medical University from January 2018 to June 2024 were retrospectively analyzed. All patients were stratified into low-risk group and intermediate-high-risk group based on the FLAIR model, a predictive model for mortality risk in amyopathic dermatomyositis combined with interstitial lung disease. Meanwhile, patients were divided into four groups according to treatment regimens: Regimen A: glucocorticoids combined with calcineurin inhibitors and cyclophosphamide; Regimen B: glucocorticoids combined with Janus kinase inhibitors with or without calcineurin inhibitors; Regimen C: glucocorticoids combined with calcineurin inhibitors; Regimen D: glucocorticoids combined with cyclophosphamide. The clinical manifestations, laboratory parameters, infection events and survival outcomes were compared among groups with different risk stratification and different treatment regimens. Multivariate logistic regression analysis was performed to identify clinical indicators independently associated with all-cause mortality. Results: Among the 82 patients with anti-MDA5⁺DM, 19 (23.2%) were males and 63 (76.8%) were females, with a median age of 50 years (range, 37-63 years). The incidence of cough was higher in the intermediate-high risk group [44 cases (74.6%)] than that in the low-risk group [10 cases (43.5%)] (χ²=7.12, P=0.008). The intermediate-high risk group also exhibited higher frequencies of expectoration [35 cases (59.3%) vs. 7 cases (30.4%), χ²=5.53, P=0.019], dyspnea [37 cases (62.7%) vs. 8 cases (34.8%), χ²=5.21, P=0.022] and fever [36 cases (61.0%) vs. 6 cases (26.1%), χ²=8.08, P=0.004]. Median serum ferritin level was 1 545.3 (936.8, 2 376.9) μg/L in the intermediate-high risk group versus 442.8 (138.9, 759.0) μg/L in the low-risk group (Z=-4.89, P<0.001). The intermediate-high risk group had significantly elevated median levels of lactate dehydrogenase [371.0 (302.0, 473.0) vs. 242.0 (208.0, 318.0) U/L, Z=-4.95, P<0.001], creatine kinase [87.0 (60.0, 254.0) vs. 45.0 (34.0, 113.0) U/L, Z=-2.83, P=0.005], carcinoembryonic antigen [6.8 (3.2, 12.5) vs. 3.8 (2.4, 6.0) μg/L, Z=-2.32, P=0.021], aspartate aminotransferase [74.0 (47.0, 133.0) vs. 45.0 (31.0, 55.0) U/L, Z=-3.44, P=0.001], C-reactive protein [7.6 (2.6, 16.3) vs. 2.4 (0.7, 5.0) mg/L, Z=-3.24, P=0.001] and erythrocyte sedimentation rate [42.0 (23.8, 63.5) vs. 23.0 (13.0, 34.0) mm/1 h, Z=-3.36, P=0.001].The prevalence of periorbital edematous erythema was significantly lower in the intermediate-high risk group [29 cases (49.2%)] compared with the low-risk group [17 cases (73.9%)] (χ²=4.12, P=0.042). The median immunoglobulin M level was markedly decreased in the intermediate-high risk group [1.2 (0.9, 1.6) g/L] relative to the low-risk group [1.7 (1.2, 2.8) g/L] (Z=-2.66, P=0.008).Complete follow-up data were obtained from 78 patients. The all-cause mortality rate (13.0% vs. 38.2%) and infection rate (6.7% vs. 57.1%) of the low-risk group were obviously lower than those of the intermediate-high-risk group. Within each risk stratum, there was no statistically significant difference in the incidence of severe infections among the four treatment regimens. Regimen A was associated with the highest survival rate among patients in the intermediate-high-risk group. Taking Regimen A as the reference, Regimens B, C and D were correlated with higher mortality risk, with corresponding OR values as follows: Regimen B OR=0.07 (95%CI 0.01-0.43, P=0.002), Regimen D OR=0.07 (95%CI 0.01-0.62, P=0.008), Regimen C OR=0.06 (95%CI 0.01-0.41, P=0.001).Multivariate logistic regression analysis revealed that rapidly progressive interstitial lung disease (RP-ILD) and dysphagia were independently correlated with mortality outcomes: RP-ILD (OR=24.95, 95%CI 1.47-422.55, P=0.026), dysphagia (OR=11.62, 95%CI 1.23-110.15, P=0.033). Positive anti-Ro52 antibody (OR=6.40, 95%CI 0.90-45.47, P=0.063) and elevated C-reactive protein (OR=1.04, 95%CI 0.99-1.10, P=0.091) showed a trend toward higher mortality risk. Conclusions: In patients with intermediate-high-risk anti-MDA5⁺DM, inflammatory biomarkers and clinical symptoms were positively associated with adverse mortality outcomes. RP-ILD and dysphagia were independently correlated with all-cause mortality. Among intermediate-high-risk patients, the regimen combining glucocorticoids, calcineurin inhibitors and cyclophosphamide was associated with higher survival probability, without an increased incidence of severe infections.