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.

Narcolepsy is a rare disorder of central hypersomnolence which is often under-recognised owing to a variable clinical phenotype. Narcolepsy type 1 (NT1) is caused by loss of hypothalamic hypocretin (orexin) secreting neurons, which function to maintain wakefulness. There is strong evidence that NT1 is an immune-mediated disorder associated with the class II human leucocyte antigen DQB1*06:02 allele. Immune checkpoint inhibitors have revolutionised the treatment of many cancers; however, through their mechanism of action, they are associated with immune-related adverse effects. We describe a complex case of NT1 following ipilimumab and nivolumab exposure for management of metastatic melanoma.

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.