Computer-aided diagnosis systems for cutaneous lesions face significant challenges in achieving both high diagnostic accuracy and computational efficiency. Current deep learning approaches often require substantial computational resources while struggling to capture the complex morphological variations inherent in skin lesions across different scales. High-order Multi-scale Parallel Vision Mamba U-Net (HMP-MUNet), a novel deep learning framework that addresses these limitations through an innovative architectural design combining State-Space Models with advanced multi-scale processing capabilities. The approach described in this study integrates a hybrid U-Net framework that combines a high-order vision state-space module for global context modeling, a multi-scale dilated attention fusion network for hierarchical feature extraction across multiple receptive fields, and a parallel multi-depth flexible network for computational optimization. This architecture uses a modified U-shaped encoder-decoder with increased channel dimensions and advanced attention mechanisms to enhance feature learning. Comprehensive evaluation on benchmark datasets shows a Dice Similarity Coefficient of 95.85% on PH2 and 90.44% on ISIC2018. The model accomplishes this superior accuracy using only 7.61M parameters, representing a remarkable 72.2% reduction compared to existing Vision Mamba architectures while maintaining high segmentation accuracy. The lightweight design shows potential for deployment across various clinical settings and imaging modalities, pending clinical validation, from specialized dermatology centers to primary care facilities. HMP-MUNet provides an automated solution for skin lesion segmentation that improves diagnostic consistency and supports clinical workflows, with potential for further validation in clinical use. The integration of high-order modeling capabilities with practical deployment considerations offers a potential solution for improving skin cancer screening protocols and expanding healthcare accessibility in computer-aided diagnosis applications.

T cells are the primary cell subset involved in antitumor immunity. Their functions depend largely on the repertoire of surface receptors. This study investigates the association between the expression of CD28 and PD-1 molecules on peripheral blood T cells and prognosis in advanced breast cancer (BC) patients undergoing paclitaxel chemotherapy, along with their roles in anti-tumor immunity.

This study evaluated the combined predictive value of tumor Ki-67 expression status, peripheral blood neutrophil-to-lymphocyte ratio (NLR), and the CD4-positive/CD8-positive T-cell ratio for short-term response assessment in patients with non-small cell lung cancer receiving PD-1/PD-L1 inhibitor therapy. We retrospectively analyzed 102 consecutive patients treated at Binhaiwan Central Hospital between January 2021 and October 2023 who completed two treatment cycles. Responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1: 13 patients achieved complete response, 26 partial response, 54 stable disease, and 9 progressive disease. For analysis, we defined response as complete response plus partial response and non-response as stable disease plus progressive disease. Univariable screening identified candidate predictors associated with response status, which were entered into multivariable logistic regression adjusted for age, Eastern Cooperative Oncology Group performance status, and smoking history, identifying Ki-67 status, NLR, and the CD4-positive/CD8-positive ratio as independent predictors of short-term response classification. Receiver operating characteristic analysis supported improved discrimination for the combined biomarker model compared with single markers, highlighting a practical, minimally invasive approach for early response stratification in this clinical setting.

Glioma represents primary malignant tumors of the central nervous system with significant incidence and mortality. Tumor angiogenesis is the hallmark of glioma pathophysiology and is an important event in the tumor environment. The aberrant structure of tumor neovascularization serves dual roles: a nutrient supply source and a metastatic portal enabling tumor cell invasion into the bloodstream. Anti-angiogenesis therapy is a hot topic in the field of cancer. Most of the previous studies focus on the activating factors and inhibitory factors of tumor angiogenesis; however, this only clarifies tumor angiogenesis in a very limited range. Abnormal protein expression or post-translational modifications contribute to the abnormal morphology of blood vessels in glioma. This protocol used laser-capture microdissection (LCM) to isolate and purify an adequate amount of neovascular tissues from glioma tissues, which was used for isotope-labelled quantitative proteomics analysis to identify differentially expressed proteins in glioma neovascular tissues compared to controls. These data provide a crucial scientific basis for elucidating the pathological mechanisms of tumor angiogenesis, discovering anti-angiogenic therapeutic targets, and constructing tumor angiogenesis-based biomarkers.

Hypoxia-inducible factors 1 and 2 (HIF-1/2) function as master regulators of cancer progression by regulating angiogenesis, cancer stem cell specification, epithelial-mesenchymal transition, immune evasion, tissue invasion, and metastasis. We utilized computer-aided drug discovery and cell-based reporter assays to identify dual HIF-1/2 inhibitors, which bind directly to highly conserved domains of HIF-1α and HIF-2α, disrupt dimerization with HIF-1β, and trigger proteasomal degradation, thereby inhibiting HIF-1/2 transcriptional activity. These inhibitors and derivative compounds block growth and vascularization of breast, colorectal, head/neck, melanoma, and prostate tumors as monotherapy, and overcome resistance to anti-CTLA-4 or anti-PD-1 immunotherapy, with an aggregate complete response rate of over 50%, through reprogramming of the tumor immune cell microenvironment. Compared with the HIF-2-selective inhibitors belzutifan and PT2385, dual HIF-1/2 inhibitor 1.21S9N showed superior activity against breast and colorectal cancer models, respectively. PT2385 caused breathing abnormalities, whereas 1.21S9N did not. The drugs are orally bioavailable, and no safety concerns were identified even after extended or supratherapeutic dosing.

The optimal sequence of administering immune checkpoint inhibitors (ICIs) and chemotherapy in advanced esophageal cancer (EC) and gastric cancer (GC) remains to be established. Understanding how this sequencing affects overall survival (OS) is crucial for optimizing treatment strategies.

Colorectal liver metastases (CRLM) are a major cause of cancer-related deaths. Glucose transporter 1 (GLUT1) is a key mediator of glycolytic metabolism in malignant and immune cells; however, the prognostic relevance of compartment-specific GLUT1 patterns in CRLM remains undefined. We hypothesized that spatial GLUT1 expression at the tumor-liver interface may reflect clinically relevant microenvironmental biology.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. The epigenetic regulator EZH2 is a promising therapeutic target due to its role in tumor progression and therapy resistance. This study combined computational and experimental methods to repurpose FDA-approved drugs as EZH2 inhibitors. Virtual screening and molecular dynamics simulations identified acetyldigitoxin (ADT) as a potent EZH2 inhibitor, demonstrating superior binding affinity (-10.90 kcal/mol) and complex stability compared to the known inhibitor GSK126. ADT formed robust hydrogen bonds and hydrophobic interactions with key residues in the EZH2 binding site, supported by favorable binding free energy calculations (ΔGbinding = -34.73 kcal/mol). In vitro, ADT exhibited selective cytotoxicity against NSCLC A549 cells (IC₅₀ = 32.4 nM) versus normal bronchial epithelial cells (IC₅₀ = 190 nM). Treatment with ADT significantly reduced EZH2 expression and potently inhibited its histone methyltransferase activity, as directly evidenced by decreased global H3K27me3 levels. ADT induced G0/G1 cell cycle arrest and promoted apoptosis, accompanied by upregulation of pro-apoptotic genes (Bax, Caspase-3) and downregulation of anti-apoptotic (Bcl-2) and cell cycle (CyclinD1) genes. Our integrated findings position ADT as a repurposed drug candidate for targeting EZH2 in NSCLC, warranting further preclinical investigation including direct enzyme inhibition assays.

We have previously defined the constitutive photomorphogenic protein 1 (COP1) gene as a therapeutic target in hepatocellular carcinoma (HCC). A recent study demonstrated that COP1 induces non-alcoholic fatty liver disease (NAFLD), a precursor to HCC, in normal hepatocytes and that reducing COP1 expression significantly improves high-fat diet-induced hepatic steatosis. Thus, in this study, we investigated if the function of COP1 was associated with HCC metabolism and evolution. Silencing of COP1 expression by a target siRNA significantly suppressed long-term colony formation in Huh7, HepG2, Huh1, and PLC/PRF/5 HCC cell lines. RNA sequencing of COP1-silenced Huh7 and HepG2 cells revealed the same directional regulation of 24 (14 up- and 10 down-regulated) genes. Notable molecular alterations were upregulation of AKR1D1 and downregulation of TMEM65, which involves negative regulation of lipid metabolism and promotion of metastasis, respectively. Correlation analysis using GEPIA2 supported inverse relationship between COP1 and AKR1D1 expression and positive relationship between COP1 and TMEM65 expression in HCC clinical samples. Targeting of COP1 reduced fat accumulation and metastatic potential in both HCC parental cells and CD133+ liver cancer stem cells. Overexpression of COP1 reversed the phenotypic changes. Collectively, our findings indicate that the COP1 is functionally correlated with HCC lipid metabolism and stemness.

Interleukin-18 (IL-18) is a pro-inflammatory cytokine, and higher IL-18 expression in pancreatic tumors is associated with poor prognosis. Although 5-fluorouracil (5-FU) has been reported to induce the release of bioactive (mature/cleaved) IL-18 from the pancreatic cancer cell line Capan-2, the underlying mechanism remains unclear. Here, we investigated IL-18 activation in pancreatic cancer cells after 5-FU treatment under low-nutrient conditions that mimic key features of the tumor microenvironment, using a monoclonal antibody we generated that specifically recognizes cleaved, active IL-18. We detected the release of active IL-18 from both Capan-2 and MIA PaCa-2 cells after 5-FU treatment. Analysis of separated attached and detached cell fractions showed that IL-18 cleavage occurred predominantly in detached cells. We also clarified that caspase-8-but not caspase-1/4-was activated in detached cells and was required for IL-18 and GSDMD cleavage that is a hallmark of pyroptosis. Surprisingly, detached cells from only nutrient starvation showed the same phenomenon, and 5-FU contributed to increased pyroptotic cells. On the other hand, the release of active IL-18 was not observed with gemcitabine. These findings suggest that a low-nutrient tumor microenvironment and 5-FU therapy can promote caspase-8-dependent pyroptotic cell death with IL-18 activation, potentially contributing to chronic inflammation in pancreatic tumors.

We present a case of diffuse hemispheric glioma (DHG), H3 G34-mutant, NEC. Postoperative histological examination and DNA sequencing detected some features consistent with DHG, H3 G34-mutant; however, no canonical H3 alterations or ATRX variants were detected. The diagnosis could only be established based on the DNA methylation profiling result. In light of these distinctive molecular findings, we propose some insights into the current WHO diagnostic criteria for DHG H3-G34 and emphasise the value of comprehensive molecular diagnosis.

During the diagnosis and treatment of non-small cell lung cancer (NSCLC), detecting the risk of its recurrence in an early phase is still challenging. Recent studies have investigated the radiomics-based machine learning (ML) models for detecting the risk of recurrence in NSCLC. However, there is still insufficient systematic evidence to prove its efficiency.

Kinesin family member 23 (KIF23) is recognised as an important tumour promoter involved in the pathogenesis of various cancers. However, its role and underlying molecular mechanisms in regulating cervical cancer (CC) growth and primary chemoresistance remain to be fully elucidated.

Accurate prediction of pathological complete response (pCR) following neoadjuvant therapy (NAT) is critical for optimizing treatment in breast cancer. This study develops and validates an interpretable, cost-effective machine learning (ML) model integrating computed tomography (CT)-based body composition parameters with routine inflammatory and nutritional biomarkers to predict pCR.

Transthoracic echocardiography and global longitudinal strain are pivotal in evaluating myocardial structure and function in cardio-oncology patients, but there are limited reports of using global longitudinal strain to identify intracardiac masses. This case presents a patient with metastatic renal cell carcinoma and cardiac metastasis that was identified using global longitudinal strain on transthoracic echocardiography and subsequently confirmed by cardiac magnetic resonance imaging.

T cell-based immunotherapies have improved outcomes in lung adenocarcinoma (LUAD), yet many patients develop primary or acquired resistance. Tumor-intrinsic mechanisms that suppress CD8+ T cell function remain incompletely understood.

Pulmonary fibrosis (PF) significantly increases the risk of lung cancer (LC), but the mechanisms underlying this transition remain unclear. This overview positions macrophage heterogeneity as a central node within the PF-LC continuum. First, we describe important subpopulations of profibrotic and pro-tumor macrophages, including SPP1+, MERTK+, TREM2+, and MARCO+ cells, using high-resolution spatial and single-cell omics technologies. Next, we analyze the fundamental mechanisms that determine their function: the fibrotic microenvironment (e.g., extracellular matrix stiffness, hypoxia) induces profound metabolic reprogramming (e.g., Warburg effect, lipid peroxidation) and stabilizes epigenetic memory (e.g., DNA methylation, histone modifications), locking them into a pathogenic state. This reprogramming occurs through two main pathways: (1) metabolic reprogramming, characterized by aerobic glycolytic conversion and dysregulated lipid metabolism, which stimulates both pathogenic functions and suppression of T cell activity; (2) Epigenetic modifications, including stabilized alterations in DNA methylation, histone modifications, and superactivator patterns, which maintain cells in a tumor-promoting phenotype. As central nodes of communication, these macrophages interact pathologically with fibroblasts and epithelial cells through secreted factors and extracellular vesicles, forming self-reinforcing feedback loops that promote disease progression. We are studying the crucial role of new technologies, particularly multi-omic spatial models and high-precision organoids, in fostering mechanistic discoveries. These discoveries pave the way for new macrophage-focused therapeutic strategies, including the precise stratification of patients using biomarkers from liquid biopsies (such as soluble SPP1 and MARCO) and the development of targeted drug delivery systems for the selective modulation of macrophage function, thus establishing a new paradigm for therapeutic interventions in pulmonary fibrosis with concomitant lung cancer.

The efficacy of immune checkpoint inhibitors (ICI) combined with chemotherapy as a neoadjuvant/adjuvant therapy for locally advanced penile squamous-cell carcinoma (PSCC) remains unclear.

The molecular link between Hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) progression remains elusive. Here, we identify glutathione peroxidase 2 (GPX2) as a pivotal mediator of this process. Single-cell analysis of HBV-positive HCC reveals a distinct GPX2+ CSC population characterized by high MYC and CD44 expression. We demonstrate that GPX2 preserves stemness intrinsically by mitigating ROS-mediated c-MYC nuclear-cytoplasmic distribution, while extrinsically fostering immune evasion via the CCL26-CCR3 signaling axis. specifically, GPX2-derived CCL26 recruits and educates B cells towards an immunosuppressive LGALS1+ state, which predicts adverse patient outcomes. In vivo, GPX2 overexpression accelerates tumorigenesis, whereas targeting CCR3 with ALK4290 sensitizes tumors to anti-PD-1 checkpoint blockade. These findings delineate a dual mechanism whereby GPX2 couples oxidative stress regulation to immune modulation, positioning the GPX2-B cell axis as a promising therapeutic target for HBV-driven liver cancer.

At initial diagnosis, approximately 30% of renal cell carcinoma (RCC) patients have de novo metastasis. This study aims to develop and validate a diagnostic nomogram for predicting cancer metastasis in patients with initially diagnosed RCC.