Tumor necrosis factor receptor-associated factor interacting protein (TRAIP) has emerged as a critical regulator of multiple oncogenic processes across various malignancies. However, its specific functional role and underlying mechanisms in breast cancer pathogenesis remain to be fully elucidated. Integrated bioinformatics analysis of TCGA and GTEx datasets was performed to assess TRAIP expression patterns. Complementary experimental validation was conducted using immunohistochemistry, qRT-PCR, and western blot in clinical specimens. Functional characterization of TRAIP in breast cancer cells was achieved through CCK-8 proliferation assays, colony formation analysis, transwell migration/invasion tests, wound healing experiments, and flow cytometric apoptosis detection. Mechanistic investigations employed co-immunoprecipitation and ubiquitination assays to delineate the TRAIP-PLSCR4 interaction, supplemented by rescue experiments to confirm functional interdependence. Consistent overexpression of TRAIP was observed in breast cancer tissues compared to normal controls. Genetic knockdown of TRAIP significantly attenuated malignant phenotypes, including: (1) reduction in cellular proliferation, (2) decrease in colony-forming capacity, (3) reduction in migratory/invasive potential, and (4) increase in apoptosis rates (Annexin V staining). Mechanistically, TRAIP functioned as an E3 ubiquitin ligase mediating proteasomal degradation of PLSCR4 through K48-linked polyubiquitination (co-IP validation). Notably, PLSCR4 silencing effectively rescued the tumor-suppressive effects of TRAIP knockdown. This study identifies a novel TRAIP/PLSCR4 regulatory axis in breast cancer pathogenesis, wherein TRAIP exerts its oncogenic function via ubiquitination-dependent degradation of tumor-suppressive PLSCR4. These findings position TRAIP as a promising therapeutic target for precision breast cancer interventions.

Helicobacter pylori (H. pylori) has been identified as a pathogenic factor in gastric cancer (GC). Building on our previous findings that VacA upregulates TRAF1, which in turn transcriptionally activates OASL, we explored the role of this TRAF1-OASL-PANoptosis axis in GC using clinical samples, cell lines, and mouse models. Functional assays (CCK-8, colony formation, migration, invasion, TUNEL) demonstrated that TRAF1 promotes GC cell proliferation, migration, and invasion via OASL, while suppressing apoptosis. RNA-seq revealed that upregulation of TRAF1 and OASL, combined with H. pylori infection in gastric epithelial cells, enriched pathways associated with PANoptosis. Rescue experiments showed that TRAF1 knockdown increased PANoptosis, and this increase was attenuated by the pan-caspase inhibitor Z-VAD-FMK, whereas subsequent OASL overexpression reversed the suppression of PANoptosis caused by TRAF1 knockdown, whereas LPS further induced PANoptosis. Both in vitro and in vivo models confirmed that H. pylori infection triggers PANoptosis. Co-Immunoprecipitation assays uncovered a protein interaction between OASL and the ZBP1-PANoptosome. Critically, under H. pylori infection conditions, OASL overexpression rescued the PANoptosis suppressed by TRAF1 knockdown in gastric epithelial cells. This study demonstrates that H. pylori infection induces PANoptosis, and defines a pathway wherein TRAF1 promotes PANoptosis by regulating OASL-mediated activation of the ZBP1-PANoptosome. Our findings reveal a novel, context-dependent duality of the TRAF1/OASL axis: it promotes PANoptosis, contributing to mucosal damage during the precancerous inflammatory stage, yet in established GC, this axis appears to suppress PANoptosis, facilitating tumor progression. These insights provide a theoretical foundation for targeting this pathway in treating H. pylori-associated gastritis-cancer progression.

Cancer-associated fibroblasts (CAFs) are central to the pancreatic ductal adenocarcinoma (PDAC) microenvironment, promoting tumor progression and therapeutic resistance. However, the expression landscape of CAF membrane proteins in PDAC remains poorly defined. We integrated scRNA-seq (n = 33; 87,949 cells), spatial transcriptomics (n = 2; 7,011 spots), and bulk RNA-seq (n = 7; 642 samples) to systematically identify PDAC-specific CAF membrane genes. A LASSO-based Cox model was developed to construct a prognostic signature, PaFMS, and evaluated through multi-cohort validation. Functional enrichment, immune infiltration, drug sensitivity, and immunotherapy response analyses were further conducted. Validation was performed using multiple database-driven analyses. We identified a PDAC-enriched myoCAF-c1 cluster closely associated with epithelial-mesenchymal transition (EMT) and angiogenesis. From this cluster, 33 candidate CAF membrane genes were defined, whose protein-protein interactions were predominantly linked to extracellular matrix organization and collagen remodeling, and spatially colocalized with myoCAF-c1 and EMT regions. An 11-gene prognostic signature, PaFMS that robustly stratified patients across six independent cohorts, achieving high predictive accuracy for overall survival. High-risk patients exhibited proliferative signaling activation, immune suppression, and reduced T/B-cell infiltration. PaFMS was associated with responses to 33 anticancer agents and predicted enhanced benefit from anti-PD-L1 immunotherapy in the low-risk group. Multi-cohort validation confirmed the expression specificity of PaFMS genes, including PLAU, TMEM158, and TRIM59. Together, these findings reveal that myoCAF-c1 promotes angiogenesis and tumor progression, and establish PaFMS as a robust CAF membrane-based prognostic model in PDAC with potential utility for precision prognosis and therapeutic decision-making. KEY MESSAGES: Integrated single-cell, spatial, and bulk RNA-seq analyses identified PDAC-specific CAF membrane genes. Discovered a PDAC-enriched myoCAF-c1 subtype linked to EMT and angiogenesis. Developed an 11-gene CAF membrane-based prognostic model (PaFMS) validated across six cohorts. PaFMS predicts patient survival, drug sensitivity, and immunotherapy response in PDAC.

Radioiodine therapy (RAIT) remains an essential tool in both treatment and restaging of pediatrics papillary thyroid carcinoma (PTC). Our aim was to describe the nuclear medicine management and outcomes of pediatric PTC patients over a 14-year period, within the context of their clinical and surgical characteristics, with particular emphasis on the role of radioiodine therapy in post-surgical treatment and disease restaging. A retrospective observational study was conducted at a reference Oncological Institute, including 35 pediatrics patients (< 18 years) diagnosed with PTC between 2010 and 2023. Demographic data, staging features, risk factors, surgical treatment, RAIT therapy, post-therapy scintigraphy, adverse effects, and follow-up outcomes were reviewed. Among the 35 patients (median age 15; 77% female), 54% had one or more risk factors, most frequently family history. Sixteen individuals presented low-risk disease, 12 had intermediate-risk characteristics, and 7 were classified as high-risk patients (according to ATA guidelines). Twenty-eight underwent total thyroidectomy (7 with lymphadenectomy), and the remaining received a hemithyroidectomy. Following thyroidectomy, twelve patients (all low-risk) were managed exclusively with clinical follow-up, without further directed treatment, while twenty-three patients received RAIT, with a mean activity of 3.5 GBq. Post-therapy imaging revealed previously undetected pulmonary metastases in 4 patients (17%), leading to disease upstaging. RAIT treatment resulted in complete remission in three of these cases. Adverse effects were mild and easily managed with symptomatic medication. After a mean follow-up of 9 years, no recurrences were reported, all patients were alive, and no long-term side effects were reported.

In this paper, we introduce and analyze a mechanical model for tumor growth that takes into account the life cycle of a tumor cell. The underlying process for tumor growth is the same as in classical mechanical models: the spatial expansion of the tumor is driven by the proliferation of the cells (mitosis) which is only limited by the pressure inside the tissue. The natural incompressibility of the cells, which leads to a movement of the cells away from regions of high pressure, is taken into account via a nonlinear Darcy's law. Compared to similar models studied recently, we include an additional variable, which represents the age of the cells. The various phases of the life of a cell (growth, mitosis and death) are then dependent on this age variable. We prove the existence of weak solutions and investigate their behavior numerically, focusing on the age distribution of the cells inside the tumor, the convergence to traveling wave solutions and the existence of a threshold for the death rate for expansion/regression of the tumor.

The global clinical trial landscape for multiple primary lung cancer (MPLC) exhibits a striking geographic anomaly. Through a systematic analysis of 8212 lung cancer registrations (2015-2024), we identified a cohort of 17 trials explicitly targeting MPLC. Analysis revealed an absolute geographic monopole: 100% of these trials were investigator-initiated in China, with a complete absence of active protocols in Western registries. We argue that this segregation is not accidental but driven by the "Asian phenotype",which is characterized by indolent, multifocal ground-glass nodules (GGNs), demands lung-sparing local strategies distinct from the systemic paradigms favored in the West. We urge the international community to transition from universal guidelines to phenotype-stratified management frameworks.

The tumor suppressor gene TP53 is the most frequently mutated gene in human cancers and has been a popular area of research in the field of oncology. The p53 protein, encoded by the TP53 gene, not only binds to many targeted genes but also regulates apoptosis, autophagy, cell cycle arrest, metabolism, senescence and the tumor immune microenvironment to suppress tumorigenesis. In recent years, an increasing number of new functions of p53 have been discovered, and p53-mediated tumor suppressor functions have been greatly expanded. Mutations in TP53 not only abolish its ability to suppress tumorigenesis but also confer carcinogenic properties to p53-mutant cells. Because of the prevalence of p53 dysfunction in various disease types, p53 has long been considered an attractive target for new anticancer drugs. However, drugs targeting p53 are still under investigation in early clinical trials and have not been approved for clinical use. This finding is consistent with the speculation that p53 is widely regarded as "undruggable." Surprisingly, several novel therapeutic approaches targeting p53, including MDM2/4 antagonists, compounds that target specific p53 mutants or restore the wild-type function of the mutated p53 protein, p53-based genetic therapies and p53-based tumor immunotherapy, have been developed in recent years. Here, we present a review of the structure, inactivation, and roles of p53 in diseases. In addition, this review discusses the efforts to target diseases associated with p53 dysfunction and the challenges encountered in the clinical development of these approaches.

Advanced ovarian cancer often presents with extensive pelvic and abdominal metastases, even malignant pleural effusion. Consequently, multivisceral resection has become the common surgical approach to achieve optimal resection of ovarian cancer. The present study aimed to evaluate postoperative complications and prognosis of multivisceral resection performed by the independent gynecologic oncologist team (GOT) or multidisciplinary team (MDT).

Desmoid tumors are fibroblast-derived rare soft tissue neoplasms with unclear borders that invade the surrounding structures. Despite the non-metastasizing nature, these tumors often relapse due to strong local aggressive behavior. The aim of this study was to analyze the demographic and clinical characteristics of patients with extraabdominal desmoid tumor, who underwent surgery between 2012 and 2022 and to determine the risk factors affecting recurrence.

The present study aimed to appraise the therapeutic outcomes of cystic lesion management and the diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in characterizing pelvic space-occupying lesions.

Esophagojejunal anastomotic leakage (EJAL) represents a severe postoperative complication following total or proximal gastrectomy. Treatment strategies include conservative management, endoscopic interventions, and surgery; however, comparative data remain limited. This study aimed to compare clinical outcomes of different strategies to identify the optimal approach based on anastomotic defect size.

Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicated Helicobacter pylori.

Patient-derived cells (PDCs) and patient-derived organoids (PDOs) are complementary preclinical models widely used in translational cancer research. However, their molecular and functional differences have not been systematically characterized. This study established and analyzed paired PDC and PDO models derived from the same gastric cancer ascites to delineate platform-dependent molecular and functional profiles.

Although gastric cancer (GC) exhibits significant genomic heterogeneity, the clinical implications of its immune microenvironment remain poorly understood.

We identified the risk factors for remnant gastric cancer (RGC) based on remnant gastric mucosal characteristics and gastritis morphology in patients undergoing distal gastrectomy.

Immune checkpoint inhibitor plus chemotherapy is the standard first-line treatment for advanced gastric cancer; however, predictive biomarkers for optimal patient selection remain unsatisfactory. This study was aimed at evaluating the predictive value of tumor mutational burden (TMB) and insertion/deletion (Indel) rate in patients with gastric cancer treated with nivolumab plus chemotherapy.

The gastrointestinal stromal tumor (GIST) is one of the most common mesenchymal tumors of the gastrointestinal tract. Between the 1990s and early 2000s, GIST was identified as a tumor characterized by KIT or PDGFRA mutations, resulting in imatinib being established as an effective targeted therapy. However, with advances in molecular diagnostics, approximately 10%-15% of GISTs have been reported to harbor alternative mutations, such as those in the succinate dehydrogenase subunit genes and BRAF, leading to the development of additional targeted therapies. GISTs exhibit a wide spectrum of clinical behaviors, ranging from indolent to highly aggressive, prompting the development of diverse risk classification systems. However, multiple systems remain in use, leading to inconsistent pathologic reports. Moreover, the mitotic counting method-a key factor in risk stratification-has become a major source of confusion among pathologists owing to the adoption of digital pathology and discrepancies between updated international guidelines and outdated reimbursement requirements. These inconsistencies have hindered pathologic reporting and communication between pathologists and clinicians. This review comprehensively overviews the historical background, molecular subtypes, and risk classification systems of GIST, focusing on evolving issues in mitotic rate evaluation and the application of risk classification systems in clinical practice.

Although the clinical importance of esophagogastric junction (EGJ) cancer is being increasingly recognized, its definition and treatment strategies vary considerably across regions. Recently, new concepts such as the gastroesophageal junction zone have been proposed for classification of EGJ cancer. Moreover, EGJ adenocarcinoma has been shown to possess a heterogeneous molecular profile consisting of both esophageal- and gastric-like phenotypes, indicating the need for EGJ-specific therapeutic strategies. Although international clinical practice guidelines for EGJ cancer have been published, substantial regional differences remain. This review aimed to summarize recent updates on the biological characteristics and management of EGJ cancers. Trials such as TIME and MIRO have demonstrated that minimally invasive surgery (MIS) reduces postoperative complications and improves the early postoperative quality of life. More recently, the MONET trial showed that MIS is not inferior to open esophagectomy in terms of long-term oncological outcomes, and the REVATE trial demonstrated the advantages of robot-assisted surgery over thoracoscopic approaches. Perioperative treatment strategies also differ across regions. Western guidelines recommend 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT)-based perioperative chemotherapy, as supported by the FLOT4 and ESOPEC trials, whereas Asian studies, such as RESOLVE and PRODIGY, have demonstrated the efficacy of docetaxel, oxaliplatin, and S-1 or S-1 plus oxaliplatin regimens. The application of immune checkpoint inhibitors is also evolving; although KEYNOTE-585 did not show a survival advantage, the MATTERHORN trial demonstrated that durvalumab plus FLOT significantly improved event-free survival, establishing a new emerging global standard. Future directions include redefining EGJ classification, implementing molecular-guided treatment selection, advancing organ-preserving strategies, and optimizing perioperative immunochemotherapy.

Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research.

The ideal timing for administering adjuvant chemotherapy following surgery for colon cancer remains a subject of debate, particularly regarding whether varying intervals should be recommended based on the presence of lymph-vascular invasion (LVI) in postoperative pathology. This study aims to evaluate the impact of the time-interval (TI) between surgery and chemotherapy on the tumor outcomes in patients with or without LVI.