Although most patients with primary central nervous system lymphoma (PCNSL) respond to treatment with high-dose methotrexate-containing regimens, over 50% relapse and 15% is refractory to treatment. The prognosis of these patients is poor, and limited treatment options exist. This report describes two patients with PCNSL who both progressed after several lines of therapy and who obtained a rapid and complete response after treatment with the bispecific antibody glofitamab. Both tolerated the treatment well without signs of cytokine release syndrome or immune-effector cell-mediated neurotoxicity syndrome. The observed responses highlight that glofitamab is a promising therapeutic option for patients with R/R PCNSL.

Targeted delivery of protein therapeutics remains challenging for translating biologics into effective treatments. Here, we introduce a universal strategy leveraging elevated glycolysis, a hallmark of many pathological states, and its resulting extracellular acidification as a navigational cue. Therapeutic proteins are encapsulated within pH-responsive polymer shells that remain near-neutral at physiological pH but gradually gain positive charge under acidic conditions. This dynamic charge modulation allows nanocapsules to sense pH gradients between healthy and diseased tissues, directing them toward pathological sites. Unlike receptor-mediated targeting that operates over nanometer scales, this receptor-independent approach enables long-range targeting. In vivo models of cancer, chronic inflammation, and acute injury demonstrate selective accumulation of encapsulated proteins at diseased sites, enhancing therapeutic efficacy while reducing systemic toxicity. By transforming a ubiquitous metabolic signature into a directional driving force, this lactate acid gradient-mediated targeting (LaGET) platform offers a previously underexplored paradigm for targeted delivery of protein therapeutics.

Glioblastoma (GBM) remains one of the most lethal adult primary brain tumors, and neurosurgical decision-making increasingly depends on integrating imaging, molecular, perioperative, and post-treatment data. Artificial intelligence (AI) methods have been proposed for several clinically relevant GBM tasks, but the literature remains heterogeneous and difficult to translate into practice.

DEK::AFF2 fusion-associated nonkeratinizing squamous cell carcinoma is a recently recognized HPV-independent entity characterized by deceptively bland morphology and potential mimicry of benign or inflammatory lesions.

For thoracoscopic resection to be successful, accurate preoperative and intraoperative localization is necessary due to the growing detection of small, non-palpable lung nodules using low-dose CT scanning. Accurate localization is required rather than optional in robot-assisted thoracic surgery (RATS) since the total lack of tactile feedback makes it extremely difficult to identify deep, tiny, and subsolid nodules. With a focus on RATS-specific criteria, this study offers a modern, clinically focused framework for technique selection. This is a narrative review of the current literature. A structured literature search was conducted in PubMed, Embase, and Web of Science from January 2015 to May 2026, and 116 relevant articles were included for qualitative synthesis. We summarized the principles, clinical efficacy, complications, and RATS‑specific adaptability of CT-guided percutaneous, bronchoscopy-assisted, and intraoperative localization techniques. No quantitative meta-analysis or bias risk assessment was performed in this study. Nodule traits, patient considerations, and institutional resources should all be taken into consideration when choosing a technique. Although percutaneous techniques have a high success rate (88-100%), there is a risk of bleeding and pneumothorax (up to 40%). First-line options for RATS are indocyanine green (ICG) fluorescence marking and microcoil localization. ICG uses robotic near-infrared channels to achieve 100% intraoperative identification and R0 resection rates, while microcoils allow sublobar resection in 90.6% of patients with 100% R0 resection. Transbronchial approaches (virtual bronchoscopic navigation [VBN], electromagnetic navigation bronchoscopy [ENB]) eliminate external marker interference and greatly lower the incidence of pneumothorax (88% reduction, 3.3% vs. 28.3% for CT-guided transthoracic aspiration, P < 0.001). Electromagnetic interference is completely avoided in next-generation shape-sensing robotic bronchoscopy. Single-stage hybrid operating room methods are favored by workflow integration. Resource-stratified approaches are suggested: low-resource settings may employ VBN/VAL-MAP or percutaneous methylene blue; mid-resource centers benefit from ENB/VBN with ICG; high-resource centers may use single-stage cone-beam CT or robotic bronchoscopy. The best RATS-compatible selection is guided by the "three-zero" approach (zero external indicators, zero transport danger, and zero electromagnetic interference). Nodule traits, patient considerations, and institutional resources must all be considered when choosing a localization technique. Precise localization is required in RATS in order to maintain negative margins, lower conversion rates, and make up for tactile deficiencies. The best balance is frequently achieved using multimodal techniques. Further increases in pulmonary nodule localization accuracy, safety, and workflow efficiency are anticipated due to ongoing advancements in robotic bronchoscopy, hybrid operating rooms, and artificial intelligence.

Cervical cancer (CC) is a common malignancy. And long non-coding RNAs (lncRNAs) have been identified as pivotal molecular modulators in tumorigenesis, with particular relevance to cervical carcinoma pathogenesis.

Pulmonary nodules are commonly evaluated using the CT-guided transthoracic biopsy; however, it is highly dependent on operator skill and can be associated with extended procedure duration and increased radiation exposure. Although robotic-assisted systems are intended to enhance procedural precision, there is limited comparative evidence against conventional techniques. Accordingly, this systematic review and meta‑analysis was conducted to compare robotic-assisted biopsy with conventional CT-guided transthoracic biopsy. We systematically searched Scopus, Web of Science, PubMed, CNKI, and the Cochrane Library until February 2026. Both randomized trials and cohort studies comparing robotic and conventional (manual) CT-guided transthoracic needle biopsy in adults were included in this review. The outcomes included procedural efficiency, diagnostic performance, radiation exposure, and safety. Meta-analysis was conducted using RevMan 5.4.1, presenting MD, RR, or OR with 95% CIs. Heterogeneity and publication bias were assessed. Nine studies were included. Compared with conventional (manual) CT-guided biopsy, the robotic approach was associated with shorter procedure time (MD = -4.94, 95% CI [-9.56, -0.32], P = 0.04) and lower radiation exposure (DLP) (MD = -211.55, 95% CI [-305.07, -118.03], P < 0.00001). Additionally, the robotic approach reduced the number of needle adjustments required, pneumothorax incidence, and overall complication incidence (RR = 0.460, 95% CI [0.290, 0.720], P = 0.0008). A reduction in the number of CT scans was observed only in the sensitivity analysis. Technical success, diagnostic yield, pulmonary hemorrhage, and chest tube placement were similar between the robotic-assisted and conventional techniques. Robot-assisted CT-guided biopsy was associated with lower radiation exposure, reduced procedural complexity, and fewer complications while maintaining comparable technical success and diagnostic yield. However, these findings should be interpreted cautiously, given the limited number of included studies, substantial heterogeneity, and observational nature of much of the available evidence. Further large prospective studies are required to validate these findings.

Morin (2',3,4',5,7-pentahydroxyflavone) is a polyphenolic dietary flavonoid found naturally in foods and has demonstrated anticancer effects in multiple preclinical models. This narrative review presents a comprehensive pharmacological analysis of morin's capacity to modulate apoptosis and autophagy, which are convergent pathways of programmed cell death (PCD) in both solid and hematological malignancies. Morin has been reported to influence intracellular reactive oxygen species (ROS) levels and disrupt the mitochondrial membrane potential (ΔΨm), thereby affecting the AMPK-mTOR-ULK1-Beclin-1 autophagic pathway. This review synthesizes preclinical data obtained from in vitro cancer cell line models, in vivo xenograft and chemical-induced tumor systems, and hypothesis-generating in silico molecular docking and network pharmacology studies. The significant crosstalk between apoptosis and autophagy appears to involve the Bcl-2/Beclin-1 pathway, cleavage of autophagy-related proteins by caspases, and shared redox stress. Mechanistic interpretation should be used with caution, as several studies have used associative molecular end points, and the accumulation of LC3-II does not equate to complete autophagic flux. Novel nanoformulation-based drug delivery strategies, the potential of chemo-sensitization in drug-resistant tumor models, and available preclinical safety and toxicology data are examined in the context of the pharmacokinetic limitations of morin, such as poor oral bioavailability, low aqueous solubility, intestinal metabolism, P-glycoprotein efflux, and limited clinical pharmacokinetic validation. Pharmacological studies suggest that morin may be classified as a multi-target phytopharmacological agent. However, more rigorous studies are required for target validation, including autophagy flux assays, clinically relevant tumor models, and pharmacokinetic optimization, before it can be translated into a therapeutic application.

Urothelial carcinoma, the predominant form of bladder cancer, represents a global public health challenge due to its high rates of recurrence and progression. At the molecular level, microRNA-21 (miR-21) has been characterized as an "oncomir" because of its ability to negatively regulate tumor suppressor genes, thereby promoting tumor survival and progression. In this context, the CRISPR/Cas9 system has emerged as a precise genome-editing tool.

To assess the impact of individual anatomical components of the PADUA score on achieving composite surgical success metrics such as MIC and Trifecta in patients undergoing RAPN, and to identify subcomponents with independent predictive value for perioperative results. Data from 3,248 consecutive patients who underwent robotic nephron-sparing surgery at nine tertiary centers between 2010 and 2023 were retrospectively analyzed. Tumors were stratified into low/intermediate (PADUA 6-9) and high complexity (PADUA ≥ 10). Primary endpoints were MIC (negative margins, warm ischemia time < 20 min, and absence of severe postoperative complications (Clavien-Dindo grade ≥ III) and Trifecta (negative margins, ischemia time not exceeding 25 min, and an uncomplicated postoperative course). Associations between individual PADUA components and outcomes were assessed using uni- and multivariable logistic regression analyses. Among the 3,248 RAPN cases, low/intermediate-complexity tumors accounted for 72.3% (n = 2,348) and high-complexity tumors for 27.7% (n = 900). MIC was achieved in 92.2% vs. 86.3% and Trifecta in 83.5% vs. 77.0% of patients with low/intermediate versus high complexity (both p < 0.001). In multivariable analysis, tumor diameter remained the sole independent anatomical predictor of MIC (OR 0.98, 95% CI 0.97-0.99; p = 0.012). For Trifecta, tumor size (OR 0.98, 95% CI 0.98-0.99; p = 0.011) and collecting system involvement (OR 0.75, 95% CI 0.61-0.94; p = 0.014) were independently linked with outcome achievement. High-complexity tumors showed increased operative duration, extended ischemia exposure, and a more pronounced decline in postoperative renal function (all p < 0.001). RAPN remains a viable option for high-complexity renal tumors, despite increased surgical challenges. Tumor size and collecting system involvement were the primary independent predictors of perioperative composite success, which may help refine preoperative risk assessment alongside composite nephrometry scores.

Many clinical trials of metastatic non-small cell lung cancer (mNSCLC) include a composite endpoint of cough, chest pain and dyspnea to assess patient-reported symptomatic deterioration using time-to-confirmed deterioration (TTCD) analyses. We sought to determine the robustness of this composite, and whether composites involving other patient-relevant symptoms of mNSCLC are more sensitive to progression.

Pleomorphic xanthoastrocytomas (PXAs) are rare brain tumors frequently associated with tumor-related epilepsy. Few studies have analyzed epilepsy outcomes in relation to tumor characteristics, clinical features, or neurophysiologic findings in this patient population.

Head and neck squamous cell carcinoma (HNSCC) is a global malignancy characterised by extremely low survival rates, primarily contributed to by late diagnosis, tumour heterogeneity, and resistance to available therapies. Deciphering reliable biomarkers is crucial for early diagnosis, prognosis and personalized therapy. This review discusses the possibilities of clusterin (CLU) as an emerging biomarker in the field of HNSCC therapeutics by incorporating insights derived from preclinical, clinical and proteomic data.

This study investigates the inhibitory effect of astragaloside II (AGS-II) on colorectal cancer (CRC) progression and elucidates the underlying mechanism involving LGALS4. The effects of AGS-II on proliferation, migration, and apoptosis of CRC cells were assessed using cell counting kit-8, colony formation, scratch wound, and flow cytometry assays. Potential targets were screened through integrated bioinformatics analysis and validated via RT-qPCR and Western blot. Molecular docking and molecular dynamics simulation were performed to evaluate the direct interaction between AGS-II and LGALS4. Functional experiments were conducted using gene overexpression and RNA interference. An in vivo xenograft model was employed to assess therapeutic efficacy. AGS-II significantly inhibited CRC cell proliferation and migration while inducing apoptosis in a dose-dependent manner. Bioinformatics analysis and experimental validation identified LGALS4 as a key target of AGS-II, with its high expression correlating with favorable patient prognosis. Molecular docking revealed a favorable binding affinity (Vina score: -9.2 kcal/mol), and molecular dynamics simulation confirmed the stability of the AGS-II-LGALS4 complex over 100 ns. Functional assays demonstrated that LGALS4 overexpression suppressed malignant phenotypes, whereas LGALS4 knockdown reversed the antitumor effects of AGS-II. In vivo experiments confirmed that AGS-II inhibited tumor growth by upregulating LGALS4. AGS-II suppresses CRC progression by upregulating LGALS4 expression, providing a novel candidate target and therapeutic strategy for CRC.

The immunosuppressive tumor microenvironment (TME) serves as a central driver of bladder cancer (BCa) progression and prognosis. While its significance is widely acknowledged, the key cellular subsets that mediate this immunosuppressive state and their core regulatory genes remain incompletely understood. Key immunosuppressive cellular subsets and their signature genes were systematically identified using single-cell RNA sequencing (scRNA-seq) data from BCa samples. A prognostic risk model was then constructed via univariate and multivariate Cox regression analyses, based on bulk RNA-seq datasets and the identified signature genes. The role of SUSD2 was further validated in vitro using qRT-PCR, Western blot, immunofluorescence, proliferation, and invasion assays. Compared with adjacent normal tissues, BCa tissues showed significant enrichment of stromal cells (e.g., epithelial cells, fibroblasts). Among these stromal populations, the proportion of myofibroblast-like cancer-associated fibroblasts (myCAFs) was significantly increased in BCa tissues, and high myCAF infiltration was closely associated with poor patient prognosis. Pseudotime trajectory analysis confirmed that fibroblast differentiation in BCa shifts toward a terminal state (State 3), which is predominantly composed of myCAFs. A prognostic model established using myCAF-related signature genes (TMEM74B, ABCC9, FCMR, ALG9, SUSD2, and ETV7) exhibited stable predictive performance in both training and validation cohorts, with SUSD2 identified as a risk-related gene. In vitro experiments revealed that SUSD2 knockdown inhibited myCAF activation and extracellular matrix secretion, thereby attenuating its promotional effects on BCa cell proliferation and invasion. The TGF-β receptor inhibitor SB-431542could reverse the facilitative effects of SUSD2 overexpression on tumor cell proliferation and migration. Our findings identify myCAFs as a core regulatory cellular subset and SUSD2 as a key molecule within the immunosuppressive TME of BCa. Additionally, SUSD2 may trigger the activation of the TGF-β/Smad signaling cascade to induce myCAF activation, thereby accelerating BCa progression. These results provide novel potential targets and a theoretical basis for prognosis assessment and TME-targeted therapy in BCa.

The contribution of fatty acid oxidation (FAO) to colorectal cancer (CRC) progression has been recognized. However, the detailed mechanisms underlying FAO remain obscure. This study explored the influence of ring finger protein 14 (RNF14) on FAO and its related mechanisms in CRC. We found that RNF14 was up-regulated in CRC, which was positively associated with FAO level. High expression of RNF14 promoted FAO to facilitate growth of CRC cells in vitro and in vivo. Mechanistically, RNA binding motif protein 15 (RBM15)/YTH N6-methyladenosine RNA binding protein 1 (YTHDF1)-mediated N6-methyladenosine (m6A) modification enhanced RNF14 translation. RNF14 reduced TATA-box binding protein associated factor 1 (TAF1) protein stability via promoting its ubiquitination. Moreover, TAF1 bound to PTEN-induced kinase 1 (PINK1) promoter to trigger its transcription. RNF14 knockdown or TAF1 overexpression repressed FAO of CRC cells, which was overturned by TAF1 or PINK1 silencing, respectively. In conclusion, RBM15/YTHDF1-mediated m6A modification of RNF14 mRNA contributed to FAO enhancement via ubiquitination of TAF1 to transcriptionally inhibit PINK1, thus promoting CRC progression.

Sentinel node navigation surgery (SNNS) minimizes unnecessary lymphadenectomy and its associated complications while enhancing detection of lymph node micrometastases through ultrastaging. A 34-year-old nulligravid woman with a history of CIN2 was diagnosed with squamous cell carcinoma (4.5 mm width, 4 mm depth) with lymphovascular invasion after conization. Clinical stage was T1a2 (FIGO 2018). Modified-radical trachelectomy with SNNS was planned for fertility preservation. SPECT-CT identified bilateral obturator and left lower para-aortic sentinel nodes. Intraoperative frozen sections revealed a 1.1 mm micrometastasis in the left obturator node and a 2.5 mm macrometastasis in the left para-aortic node. The procedure was converted to modified-radical hysterectomy with bilateral adnexectomy and pelvic lymphadenectomy, followed by concurrent chemoradiotherapy including the para-aortic field. The patient remains disease-free at 10 months. Without SNNS, the para-aortic metastasis would have been undetected, resulting in inadequate radiation coverage. SNNS fundamentally changes therapeutic approaches by enabling accurate disease extent identification and individualized treatment.

Background: Gastric cancer (GC) is characterized by late-stage diagnosis and a lack of reliable non-invasive biomarkers. This study aims to investigate the plasma bile acid (BA) profile to enhance the understanding of GC metabolism and identify potential diagnostic and prognostic tools. Methods: In a case-control design, 62 GC patients (stages I III) and 70 matched controls were recruited. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), the concentrations of 48 metabolites in plasma were measured. Statistical analysis included univariate tests, principal component analysis, and linear discriminant analysis (LDA). Results: GC patients showed a significantly lower CA/CDCA ratio and alterations in secondary and conjugated bile acids, including TLCA, GLCA, TDCA, GDCA, and GUDCA, suggesting involvement of the gut liver microbiome axis. The ability to distinguish between groups was moderate (AUC = 0.731). Furthermore, BA levels were negatively correlated with tumor stage, tumor size, and systemic inflammatory markers (CRP, mGPS), while they were positively correlated with nutritional and hematological markers such as albumin and hemoglobin. Conclusions: Gastric cancer is associated with a distinct circulating BA profile that reflects not only tumor-related metabolic remodeling, but also systemic inflammation, nutritional status, and disease burden. The reduced CA/CDCA ratio and alterations in secondary and conjugated bile acids support the involvement of the gut-liver-microbiome axis in GC biology. Although BA profiling alone showed moderate diagnostic performance, its integration with conventional tumor markers, inflammatory indices, and clinico-pathological parameters may improve multimodal biomarker panels for noninvasive patient stratification, disease assessment, and future prognostic evaluation.

Triple-negative breast cancer (TNBC) remains one of the most lethal breast cancer subtypes, driven by early dissemination and resistance to therapy. Here, we reveal a macrophage-centered cytokine circuit that fuels TNBC metastasis and immune evasion. Tumor cells reprogram naïve macrophages into tumor-associated macrophages (TAMs) that secrete CCL3, CCL4, CXCL2, and IL-1β, collectively promoting epithelial-to-mesenchymal transition, migration, transendothelial invasion, and lung colonization. These TAMs, in turn, convert naïve CD4⁺ T cells into FOXP3⁺ Tregs, establishing a self-reinforcing immunosuppressive niche. Pharmacological inhibition of CCR5, CXCR2, and IL1R1 with maraviroc, navarixin, and anakinra, respectively, disrupted this cytokine axis, suppressing metastatic colonization in vivo. Our findings reveal that blocking cytokine receptor signaling disrupts the pro-metastatic crosstalk between macrophages and TNBC cells, offering a clinically actionable strategy to restrain metastasis and overcome therapy resistance in TNBC.

Research on amnesia has been fundamental in establishing the role of the human hippocampus in memory. Even though other structures within the hippocampal-diencephalic-cingulate network also play a role in episodic memory, studies of hippocampal amnesia often ignore the importance of changes in this broader network. In a large cohort of patients (n = 38) with hippocampal damage due to autoimmune limbic encephalitis, we previously found that amnesia was predominantly explained by resting-state functional abnormalities across this network. Here, we examined the integrity of individual diencephalic nuclei and white matter pathways, and its relationship with memory function. We found atrophy in the mammillary bodies, and the anterior, laterodorsal, pulvinar, and dorsomedial thalamic nuclei. Atrophy was often as pronounced as that in the hippocampal formation. Diencephalic volumes predicted memory over and above any hippocampal/subicular subfield volume estimate. White matter was compromised within and beyond this network. Fornix integrity was linked to diencephalic and hippocampal volumes, but not to recollection/recall. We strongly advise caution in employing the term "focal hippocampal damage" in cognitive neuroscience, and highlight the need to study the significance of plausibly knock-on effects in specific diencephalic nuclei and white matter tracts within broader circuits.