Neoadjuvant immunotherapy has demonstrated satisfactory efficacy for high microsatellite instability/mismatch repair deficiency (dMMR/MSI-H) in locally advanced colorectal cancer (LACRC). This study aims to evaluate the safety and short-term efficacy of neoadjuvant immunotherapy for patients with LACRC.

This study aims to investigate the molecular mechanisms underlying germ cell tumors (GCTs), focusing specifically on seminomas and teratomas. By analyzing gene expression profiles and miRNA interactions, the goal is to identify key regulatory miRNAs and signaling pathways that differentiate these tumor types and could serve as important regulators for therapy development. Raw data for seminomas and teratomas were extracted from the GEO database, and gene hubs were identified using STRING and Gephi. Signaling pathways and functional annotations were analyzed using miRPathDB, while miRNA-gene interactions were explored via miRWalk. Hub miRNAs were filtered and confirmed using miRDB. This study highlights significant changes in gene expression diversity between tumor and normal gonadal tissues, providing insights into the molecular dynamics of seminomas and teratomas. Distinctions between seminomas and teratomas were identified, shifting the focus toward miRNAs to discover more precise and novel therapeutic approaches. The hub genes of seminomas and teratomas were identified separately. MiRNAs targeting these hub genes were also determined and confirmed. These miRNAs collectively influence essential oncogenic pathways-confirming hsa-miR-138-5p as a regulator of pathways such as Hippo signaling, transcriptional misregulation in cancer, and microRNA cancer signaling in seminomas, and hsa-miR-200b-3p as a regulator of p53 signaling, T cell receptor signaling, and pathways including PI3K/AKT, MAPK/ERK, and Wnt/β-catenin in teratomas-confirming their potential as promising candidates for subtype-specific therapeutic intervention. MiRNAs identified through bioinformatics analyses, and their predicted regulatory roles in key oncogenic pathways, represent potential therapeutic targets or regulators of biological processes. However, further experimental validation is needed to confirm these findings.

UDP-Gal-β-1,4 galactosyltransferase-V (GalT-V) is a member of a large family of galactosyltransferases whose function is to transfer galactose from the nucleotide sugar UDP-galactose to a glycosphingolipid glucosylceramide, to generate lactosylceramide (LacCer). It also causes the N and O glycosylation of proteins in the Trans Golgi area. LacCer is a bioactive lipid second messenger that activates an "oxidative stress pathway", leading to critical phenotypes, e.g., cell proliferation, migration angiogenesis, autophagy, and apoptosis. It also activates an "inflammatory pathway" that contributes to the progression of disease pathology. β-1,4-GalT-V gene expression is regulated by the binding of the transcription factor Sp-1, one of the most O-GlcNAcylated nuclear factors. This review elaborates the role of the Sp-1/GalT-V axis in disease phenotypes and therapeutic approaches targeting not only Sp-1 but also Notch-1, Wnt-1 frizzled, hedgehog, and β-catenin. Recent evidence suggests that β-1,4GalT-V may glycosylate Notch-1 and, thus, regulate a VEGF-independent angiogenic pathway, promoting glioma-like stem cell differentiation into endothelial cells, thus contributing to angiogenesis. These findings have significant implications for cancer and cardiovascular disease, as tumor vascularization often resumes aggressively following anti-VEGF therapy. Moreover, LacCer can induce angiogenesis independent of VEGF and its level are reported to be high in tumor tissues. Thus, targeting both VEGF-dependent and VEGF-independent pathways may offer novel therapeutic strategies. This review also presents an up-to-date therapeutic approach targeting the β-1,4-GalT-V interactome. In summary, the β-1,4-GalT-V interactome orchestrates a broad network of signaling pathways essential for maintaining cellular homeostasis. Conversely, its dysregulation can promote unchecked proliferation, angiogenesis, and inflammation, contributing to the initiation and progression of multiple diseases. Environmental factors and smoking can influence β-1,4-GalT-V expression and its interactome, whereas elevated β-1,4-GalT-V expression may serve as a diagnostic biomarker of colorectal cancer, inflammation-exacerbated by factors that may worsen pre-existing cancer malignancies, such as smoking and a Western diet-and atherosclerosis, amplifying disease progression. Increased β-1,4-GalT-V expression is frequently associated with tumor aggressiveness and chronic inflammation, underscoring its potential as both a biomarker and therapeutic target in colorectal and other β-1,4-GalT-V-driven cancers, as well as in cardiovascular and inflammatory diseases.

An oxysterol, 25-Hydroxycholesterol (25OHChol), is produced through cholesterol oxidation and is involved in various cellular processes, including apoptosis. However, the precise mechanisms underlying 25OHChol-induced apoptosis in neuroblastoma cells remain unclear. The aim of this study was to elucidate the detailed molecular mechanisms by which 25OHChol induces apoptosis in human neuroblastoma cells. This study explores the apoptotic effects of 25OHChol and the associated signaling pathways in BE(2)-C cells, a widely used human neuroblastoma cell model for neuronal differentiation and cancer research. To evaluate the cytotoxicity of 25OHChol, cell viability was assessed using the CCK-8 assay, which demonstrated a concentration-dependent decline, indicating a potential induction of cell death. Morphological changes characteristic of apoptosis, such as nuclear condensation and fragmentation, were confirmed via DAPI staining. Additionally, Annexin V/PI flow cytometry analysis revealed an increase in late apoptotic cell populations, further corroborating apoptosis induction. To investigate the molecular mechanisms, we analyzed the expression of Bcl-2 family proteins via Western blotting. The results showed an elevated Bax/Bcl-2 ratio, suggesting activation of the intrinsic mitochondrial apoptotic pathway. This was further supported by a reduction in mitochondrial membrane potential (MMP), as measured by flow cytometry. Increased caspase-9 and caspase-3/7 activity provided additional evidence for caspase-mediated apoptosis. Moreover, treatment with the pan-caspase inhibitor Z-VAD-FMK led to a dose-dependent increase in cell viability, confirming the essential role of caspases in 25OHChol-induced apoptosis. In conclusion, this study demonstrates that 25OHChol triggers apoptosis in BE(2)-C neuroblastoma cells through activation of the intrinsic mitochondrial apoptotic pathway. These findings provide new insights into the cytotoxic effects of 25OHChol and its potential role in neuroblastoma cell death.

Artificial intelligence (AI) and its machine learning and deep learning algorithms have shown promise in oncological practice. Spatial information analysis in the context of cancer is crucial for its diagnosis and treatment because it can provide an understanding of tumor-microenvironment interactions and reveal insights into response to treatment. AI tools can analyze spatial information at multiple scales, highlighting key disease, clinical, and genetic phenotypes that may reveal underlying mechanisms and molecular markers of response and resistance within the tumor and its microenvironment. By examining tumor interactions at macroscopic (diagnostic imaging) and microscopic (pathology slides and spatial biology) levels, AI can assist in making important diagnostic and prognostic decisions. In this review, we first present an overview of AI and the need for multiscale spatial information in oncology. Then, we examine growing AI applications in the analysis of such information, focusing on diagnostic imaging, digital pathology, and spatial molecular biology. We also discuss applications of large-scale foundation models and task-oriented agentic AI in these fields as emergent technologies. Then, we discuss current limitations for the clinical translation of AI into regular utilization in cancer care and discovery.

C-C motif chemokine receptor-like 2 (CCRL2) is an atypical chemokine receptor (ACKR) that binds chemerin with high affinity but lacks classical G protein-coupled signaling. Instead, it functions as a non-signaling presenter of chemerin to CMKLR1-expressing cells, modulating antitumor immunity. CCRL2 is highly expressed in the tumor microenvironment and various human cancers, and its expression has been linked to delayed tumor growth in mouse models, primarily through the chemerin/CMKLR1 axis. While CCRL2's role in immune surveillance is well established, its tumor cell-intrinsic functions remain less clear. Here, we investigated the impact of CCRL2 overexpression and knockout on tumor cell behavior in vitro. Although CCRL2 did not affect proliferation, migration, or clonogenicity in B16F0 melanoma and LLC cells, it significantly influenced spheroid morphology in B16F0 cells. Transcriptomic analysis revealed that CCRL2 modulates innate immune signaling pathways, including TLR4 and IFN-γ/STAT1, with context-dependent downstream effects. These findings suggest that CCRL2 shapes tumor architecture by rewiring inflammatory signaling networks in a cell-intrinsic manner. Further studies in other cancer types and cell models are needed to determine whether CCRL2's regulatory role is broadly conserved and to explore its potential as a therapeutic target in solid tumors.

Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial-mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria.

Ovarian cancer is a deadly gynecological malignancy that will affect about 21,000 women and result in almost 153,000 deaths in the United States in 2025. New clinical tools that facilitate early diagnosis and treatment of ovarian malignancies will significantly help reduce mortality and improve current long-term survival rates. We utilized a previously identified single-strand DNA aptamer RLA01 that binds and internalizes into target epithelial ovarian cancer cells to label PLGA-based nanoparticles and determine their ability to selectively target EOC cells and deliver payloads for cellular internalization. Nanoparticles labeled with RLA01 significantly enhanced cellular uptake 20-85% by receptor-mediated endocytosis into target EOC Caov-3 cells and inhibited cellular uptake in non-target HOSE 6-3 cells. Further, labeling of paclitaxel-loaded nanoparticles with RLA01 significantly decreased cell proliferation and induced apoptosis. A preliminary pilot study looking at the in vivo stability of aptamers demonstrated their ability to promote retention and honing of nanoparticles at tumors. These data demonstrate the effective combinatorial use of aptamer RLA01 and nanoparticle technologies for the direct targeting of tumor cell populations both in vitro and in vivo.

Colorectal cancer (CRC) is not only the third most common cancer worldwide, with 1.1 million new cases per year; it is also the second leading cause of cancer death. However, mortality has decreased since 2012 due to early detection programs and better therapeutic approaches. While many patients are diagnosed at an early stage, there is up to 50% relapse after optimal initial treatment. Therefore, it is crucial to explore the mechanism underlying the development of recurrences and metastasis. It is known that tumors release dormant cells that escape chemotherapy and nest in a target organ without proliferating. Under certain circumstances that are not yet entirely clear, they can be activated and metastasize. Therefore, the objective of this work is to explore the detailed mechanisms of dormancy, including early detection of recurrence and therapeutic approaches for the treatment of CRC. The specific objectives are to determine biomarkers that may be useful in identifying dormant cells to detect minimal residual disease (MRD) after surgery and predicting disease progression, as well as evaluating biomarkers that are susceptible to therapeutic intervention.

Magnetic resonance imaging (MRI) has a pivotal role in both pretreatment staging and post-treatment evaluation of rectal cancer. This study presents an innovative deep learning model, CAAFE-ResNet18*, based on the residual neural network ResNet18*. The model features an ingeniously designed feature extraction and complementation module (i.e., CAAFE), which leverages a multiscale dilated convolution parallel architecture combined with a channel attention mechanism (CAM) to achieve multilevel information fusion, spatial feature enhancement and channel feature optimisation. This enables in-depth exploration and augmentation of multilevel downsampled features, significantly improving feature representation capability and overall performance. Testing on rectal cancer MRI data demonstrates that the CAAFE-ResNet18* model significantly outperforms convolutional neural network (CNN) backbone networks and recent state-of-the-art (SOTA) models. This result indicates that the CAAFE model, by complementing and extracting MR images of patients with locally advanced rectal cancer (LARC) features at different scales from ResNet18*, may help to identify patients who will show complete response (CR) at the end of treatment and those who will not respond to therapy (NR) at an early stage of the treatment.

Achieving optimal surgical margins is critical in breast-conserving surgery (BCS) to reduce local recurrence (LR) and the need for re-excision. This meta-analysis evaluated the impact of intraoperative margin optimization strategies on key surgical and oncologic outcomes in patients who underwent BCS.

Acral melanoma (AM) is the predominant subtype of melanoma in Asians. Early detection and prevention can significantly improve patient outcomes; however, there is a lack of effective early biomarkers for predicting AM metastasis. Here, we employed single-cell and spatial transcriptomics analyses to investigate early microsatellite lesions of AM and identify biomarkers of invasiveness in these lesions. Our results characterize a highly immunosuppressive microenvironment and metabolic process shifts in early AM microsatellite lesions that promote the metastatic potential. The transcription factor SOX6 is overexpressed in microsatellite lesions and marks a population of highly invasive melanoma cells. The pro-invasive role of overexpressed SOX6 was validated in vivo and in vitro, including its ability to enhance tumor invasion by upregulating cellular glycolysis, disrupt fatty acid transport, and increase intracellular phosphatidylcholine content. This study suggests that SOX6-overexpressing melanoma cells are the main driver subpopulation promoting early invasion of AM and establishes SOX6 and fatty acid transport processes as biomarkers and potential therapeutic targets for early melanoma metastasis.

Pathologically, intrahepatic cholangiocarcinoma (ICC) is classified into small-duct (SD) type and large-duct (LD) type, each with distinct clinicopathological characteristics. The contrast-enhanced ultrasound (CEUS) features of the two ICC types remain insufficiently explored.

Nutritional risk assessment indices impact disease prognosis, yet their prognostic roles in preoperative digestive system tumor (DST) patients remain unclear.

Accurate delineation of Gross Tumor Volume (GTV) in lung cancer is critical for effective radiotherapy and surgical planning. However, segmentation of GTV in high-resolution CT images remains challenging, particularly when tumors are small or have indistinct boundaries.

Conversion immunochemotherapy may enable curative surgery in patients with initially unresectable locally advanced gastric cancer, but its response rate remains low. Little evidence has shown how to easily predict therapeutic efficacy from hematological biomarkers, apart from tissue biomarkers. This study aimed to identify predictive factors for treatment response from hematological biomarkers and propose strategies for non-responsive patients.

Clinical studies demonstrate that comorbidity between colorectal cancer (CRC) and depression is common, leading to a higher mortality risk among CRC patients. However, the mechanisms remain largely unexplored. The role of core brain regions in comorbidity of CRC and depression and whether modulating these regions can improve both depression-like symptoms and CRC progression have yet to be clarified. In this study, we establish a mouse (Mus musculus) model of CRC and observe that mice with orthotopic colorectal cancer (CRC mice) display depression-like behaviors. Through c-FOS mapping, network analysis, correlation analysis, and inverse tracing, we identify the anterior cingulate cortex (ACC) as a central node within the depression-related brain network in CRC mice. Notably, inhibiting ACC activity not only alleviates depression-like behaviors but also mitigates CRC-induced neuronal damage and reduces CRC tumor progression. These findings underscore the critical role of the ACC in comorbidity of CRC and depression and suggest that ACC-targeted interventions may hold therapeutic potential for CRC patients with comorbid depression.

Local treatment of pelvic Ewing Sarcoma (EWS) is czhallenging due to complex anatomy and potential complications. Local therapy may be deferred to maintain chemotherapy dose-intensity, but the impact of this delay on outcomes remains unclear.

Breast cancer has become one of the most common malignant tumors in women, and the incidence rate is increasing annually in men. This study focused on exploring the prognostic significance of the combined detection of serum ALP and LDH in patients with breast cancer. We enrolled 80 individuals with male breast cancer (MBC), female breast cancers (FBCs) were randomly matched via propensity score matching (PSM). In the MBC cohort, the optimal cutoff values for ALP and LDH were determined to be 114 U/L and 207 U/L, respectively, whereas in the FBC cohort, they were 68 U/L and 133 U/L, respectively. There was a difference in median survival between patient groups classified by the optimal cutoff values of ALP and LDH in the FBC cohort. However, in the FBC cohort, there was no significant correlation between the levels of ALP or LDH and patient prognosis. We developed a "joint score" system that incorporates the values of both ALP and LDH and separates MBCs into three groups. Survival was significantly different among the three groups. In the multivariate analysis, the "joint score" was identified as an independent prognostic factor for both disease-free survival(DFS) and overall survival (OS).

Gastric MALT lymphoma diagnosis relies on histopathological findings and immunoglobulin H gene (IgHr) rearrangement testing, which reflects monoclonal immunoglobulin proliferation. This study aimed to clarify the role of IgHr in the diagnosis, treatment prediction, and surveillance of gastric MALT lymphoma. Of the 152 suspected cases, 131 were definitively diagnosed using a combination of IgHr and pathology, with pathological findings considered the gold standard. Patients with discrepancies between IgHr and pathology underwent re-evaluation. The relationship between IgHr status, clinicopathological features, and treatment outcomes was analyzed. IgHr and histopathology were assessed over 2 years in 41 patients after pathological complete remission (pCR). IgHr positivity was 69.5% at initial biopsy and 90.8% after two biopsies. IgHr-positive cases had higher H. pylori infection rates and better CR rates post-eradication. Patients with IgHr positivity at pCR had higher recurrence rates (16.7%). IgHr positivity gradually declined among 37 non-recurrent cases (CR: 56.8%, 6 M: 45.9%, 1Y: 21.6%, 2Y: 10.8%), indicating a delay between pCR and IgH-negative conversion. Repeated biopsies may improve the accuracy of gastric MALT lymphoma diagnosis. IgHr-positive status at pCR may signal higher recurrence risk, underscoring the need for careful post-CR surveillance. Surveillance should account for potential delays in IgHr-negative conversion.