Cancer-associated fibroblasts (CAFs) play critical roles in tumor progression and immunosuppression; however, their contribution to the functional classification and personalized treatment of gastric cancer remains poorly defined. This study aimed to identify effective therapeutic targets to facilitate individualized treatment strategies for patients with gastric cancer.

Prostate cancer is the second most common fatal cancer in men. Identifying new biological therapeutic targets is crucial to effectively improve the prognosis of prostate cancer patients. Ovarian tumor family deubiquitinase 4 (OTUD4) is a member of the ovarian tumor-associated protease domain (OTUDs) family. Although previous studies have shown that the expression and function of OTUD4 vary across different tumors, its role in prostate cancer remains unknown. The aim of this study is to explore new therapeutic targets and diagnostic markers for prostate cancer and investigate their mechanisms of action.

An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer (SCLC). The systematic review aimed to summarize the characteristics of ferroptosis from its pathogenetic role to translational therapeutic implications in SCLC.

A 15-month-old intact female rat was presented with worsening lethargy and dysorexia present for 1 wk and bruxism present for 3 d. The diet was fruits, vegetables, and granola. On presentation, the rat was mildly dehydrated and had marked incisor malocclusion with enamel hypoplasia. On oral examination, the left mandibular molars were not visible and the gum line was prominent. Black punctate enamel discoloration was observed multifocally on molars, but no mucosal lesions were observed. The incisors were trimmed and the rat was discharged with analgesics, supportive care, and dietary recommendations. The rat's condition continued to deteriorate and, 1 wk later, a left mandibular mass appeared that the owner perceived as painful. Computed tomography of the head showed lysis of the body of the left mandible, absence of left mandibular molar teeth, and abnormal soft-tissue attenuation in the left tympanic bulla. On the last visit (Day 31), purulent discharge was visible in the left external ear canal and along the left mandibular gingiva. Fine-needle aspiration and cytology of the mandibular mass suggested a keratinizing epithelial tumor of benign appearance. Euthanasia was elected, based on the poor prognosis. Histopathological examination revealed a well-differentiated oral squamous cell carcinoma of the left mandibular region with ipsilateral subacute purulent otitis media. Key clinical message: Squamous cell carcinoma should be included in the differential diagnosis of an infected, non-ulcerated oral mass in a rat.

Canine lymphoma is the most common hematopoietic malignancy, but the primary mediastinal form is rare. Progression from this form to systemic multicentric lymphoma has not been clearly documented in veterinary medicine, and optimal treatment strategies remain uncertain. This report describes a case of primary mediastinal T-cell lymphoma in a young dog that progressed to multicentric disease and was managed with chemotherapy and radiation therapy. A 2-year-old castrated male Shetland sheepdog was referred for evaluation of a cranial mediastinal mass detected on thoracic radiographs. On physical examination, bradycardia was noted, with all peripheral lymph nodes within normal limits. Laboratory abnormalities included severe hypercalcemia, elevated symmetric dimethylarginine, and the presence of large lymphocytes on blood smear. Cytology, polymerase chain reaction for antigen receptor rearrangements, and flow cytometry confirmed CD4+ T-cell mediastinal lymphoma. Initial treatment with the 25-week L-CHOP protocol achieved complete remission, but relapse occurred at Week 8, prompting radiation therapy to the mediastinal and submandibular masses. These lesions regressed but generalized peripheral lymphadenomegaly and a splenic honeycomb pattern developed, indicating progression to multicentric lymphoma. Based on ex vivo drug sensitivity testing, lomustine was initiated as rescue chemotherapy, achieving a second complete remission. Nevertheless, relapse occurred 38 d after the initial lomustine administration, and the dog ultimately died. Key clinical message: This case highlights the fact that progression from primary mediastinal to multicentric lymphoma may be associated with a poor prognosis in dogs. Radiation therapy demonstrated potential efficacy and warrants further investigation as a treatment option for canine mediastinal lymphoma.

The majority of locally advanced esophageal squamous cell carcinoma (ESCC) patients do not achieve a pathological complete response (NPCR) after neoadjuvant chemoimmunotherapy (NCIT), and their prognosis exhibits significant heterogeneity. This study aimed to establish a pathological subtyping system for NPCR patients to guide precision adjuvant therapy.

Natural killer (NK) cells, critical components of innate immunity, possess the ability to eliminate tumor cells without prior sensitization. In gliomas, particularly glioblastoma, the tumor microenvironment (TME) exerts potent immunosuppressive effects that impair NK cell function through MHC-I overexpression, secretion of TGF-β and IDO, and recruitment of myeloid-derived suppressor cells (MDSCs). Emerging evidence highlights the significance of NK cell infiltration, cytotoxicity, and ligand-receptor dynamics-such as NKG2D, KIRs, and CX3CR1+ subsets-in shaping prognosis and therapeutic responsiveness in glioma patients. Therapeutic strategies including activation of NK cells via chemotherapeutics (bortezomib, decitabine), blockade of inhibitory receptors (NKG2A, CD161), and combinatorial approaches with immune checkpoint inhibitors are under active investigation. Notably, chimeric antigen receptor (CAR)-engineered NK cells targeting EGFR, HER2, GD2, and CD133 show promise in preclinical glioma models due to their enhanced specificity and reduced toxicity compared to CAR-T cells. This review summarizes the multifaceted roles of NK cells in glioma immunity and highlights novel immunotherapeutic strategies to restore NK cell function and improve clinical outcomes.

Glioblastoma (GBM) remains the most prevalent and aggressive primary central nervous system (CNS) malignancy; however, the clinical efficacy of the preferred chemotherapeutic agent, Temozolomide (TMZ), is severely compromised by innate and acquired resistance. Sphingolipid metabolism acts as a pivotal regulator of GBM cell fate, and the imbalance of the "sphingolipid rheostat" is intimately linked to TMZ resistance. This provides potential targets for developing novel prognostic models to inform stratified treatment risk strategies, while offering a promising entry point for TMZ chemosensitization and stratified drug combinations.

Active surveillance for low-risk papillary thyroid carcinoma (PTC) is hampered by the lack of reliable biomarkers to distinguish indolent from progressive tumors. While our previous single-cell analysis identified tumor-infiltrating B cells as key determinants of indolent PTC, their clinical utility remains constrained by low abundance and peripheral undetectability. We therefore employed Mendelian randomization (MR) to investigate this causal relationship and assess the potential of peripheral B-cell profiling as a non-invasive strategy for distinguishing indolent PTC.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a complex tumor ecosystem that contributes to its progression. Deubiquitinases (DUBs) are vital regulators in cancer. However, the overall activity of DUBs and their role in driving PDAC progression within immune microenvironment remain largely unknown.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, with immunotherapy yielding <10% objective response rates (ORR) due to its profoundly immunosuppressive tumor microenvironment (TME). This review integrates preclinical and clinical evidence (2018-2026) to dissect how stromal desmoplasia, myeloid dominance, T-cell exclusion, and impaired antigen presentation converge to form an immune-privileged niche. Key resistance pathways, including cGAS-STING, Hedgehog, and NF-κB, are discussed alongside emerging strategies such as CAR-T cells, mRNA neoantigen vaccines, STING agonists, CD39/CD73 blockade, and cDC1-based vaccines. Despite incremental progress, durable responses remain rare, emphasizing that single-target interventions are insufficient. We propose a "3D+R" framework, De-desmoplasia, De-adenosine, De-novo antigen, and Rational sequencing, to guide multidimensional, biomarker-driven immunotherapy design. Approaches such as timed cDC1 vaccination, patient-tuned STING agonism, and metabolic checkpoint inhibition exemplify how PDAC's immune-desert phenotype may be reshaped toward an immune-reactive state. Conceptualizing PDAC as a dynamic immune ecosystem rather than a mutation-driven entity may ultimately transform sporadic responses into durable and predictable clinical benefit.

Pheochromocytomas (PCCs) are rare neuroendocrine tumors with limited treatment options once metastasized. Progress toward effective therapies has been hindered by their rarity, disease heterogeneity, and lack of representative preclinical models. Organoids are three-dimensional, self-renewing structures that recapitulate key features of their tissue of origin, providing valuable platforms for disease modeling, drug screening, and personalized medicine. This study aimed to establish and characterize patient-derived organoid cultures of PCCs.

Epithelioid hemangioendothelioma (EHE) of bone is a malignant vascular neoplasm with a very low global prevalence. Nonspecific clinical and histopathological findings make the diagnosis of this tumor very challenging. In this case, we reported a 23-year-old male presented with persistent right buttock pain for 9 months (VAS 2-3). No other clinical findings were found. On plain radiographs, a lytic lesion was found on the right iliac wing. MRI showed iso- hyperintense lesions on both T1- and T2-weighted sequences with hemorrhagic components. A CT guided core needle biopsy was performed for further evaluation. The patient underwent wide excision with adjuvant chemotherapy. At six months post-surgery, lymph node metastases was found on PET scan without any clinical symptoms. A comprehensive interdisciplinary evaluation is required to establish the diagnosis of EHE.

Chondrosarcoma is a malignant tumor originating from cartilage-producing cells. Although rare in the hand, it is the most common primary malignant bone tumor in this location. We present a case of high-grade chondrosarcoma of the first metacarpal bone in an 85-year-old female, who presented with pain and severe limitation of hand function. Imaging studies initially suggested a giant cell bone tumor, and a tru-cut biopsy did not confirm chondrosarcoma. During the preoperative period, the tumor enlarged from approximately 10x9 cm to 15x11 cm, ultimately necessitating amputation as the treatment of choice. Histopathological evaluation revealed grade 2-3 chondrosarcoma. According to the existing literature, a hand chondrosarcoma of this size has not been previously documented. Hand chondrosarcomas, unlike those in other regions, rarely metastasize; however, despite their low metastatic potential, they may still lead to substantial morbidity. When wide resection and amputation are performed, as in our case, the risk of local recurrence is significantly reduced.

Colorectal cancer (CRC) remains a major global health challenge, with current therapeutic options often limited by drug resistance and adverse effects. Small molecules provide distinct advantages, including oral bioavailability, cost-effectiveness, and the ability to target intracellular pathways critical for tumor progression. In this study, we designed and synthesized a new series of pyrazolone derivatives with varied substitution patterns using microwave-assisted methods and evaluated their antiproliferative activity against CRC cell lines (HCT-116 and WiDr). Among these, PL-13 emerged as a potent and selective candidate, exhibiting strong cytotoxicity toward cancer cells while sparing noncancerous CRL-1459 colon cells. Functional assays, including colony formation and wound healing, confirmed its ability to inhibit cell proliferation and migration. Western blot analyses demonstrated that PL-13 induces apoptosis via the intrinsic mitochondrial pathway, as evidenced by increased levels of cleaved caspase-9 and PARP, and modulates LC3A/B expression, suggesting involvement of autophagy. Kinome profiling revealed selective binding of PL-13 to FLT3, which was validated by an IC50 value of 8.2 μM. Molecular docking further supported these findings, showing favorable binding energy (-7.98 kcal/mol) compared to regorafenib (-7.13 kcal/mol). Collectively, these results highlight PL-13 as a promising lead compound for further optimization toward CRC therapy.

ObjectiveThis study aimed to investigate the clinical diagnostic performance of a combined classification model incorporating magnetic resonance imaging (T1WI-CE) habitat and human epididymis protein 4 (HE4) for differentiating borderline ovarian tumors (BOTs) from malignant epithelial ovarian tumors (MEOTs).MethodsA retrospective analysis was conducted on 127 patients with pathologically confirmed ovarian tumors, including 62 with BOTs and 65 with MEOTs, all of whom underwent preoperative magnetic resonance imaging examination. Twenty habitat features, including the original images, were extracted. T1WI-CE was used to extract 2395 radiomics features from two habitat subregions. Feature selection was performed using correlation analysis and least absolute shrinkage and selection operator regression.ResultsThe combined classification model had the highest area under the curve, 0.941 in the training group and 0.880 in the test group, thus outperforming the habitat area and clinical data classification model. The DeLong test demonstrated statistically significant differences between the combined classification model and the clinical classification model, with P values of 0.041 in the training group and 0.023 in the test group. Additionally, a statistically significant difference was observed in the DeLong test results between the cystic habitat subregion (H2) and the overall habitat region.ConclusionsThe combined classification model of habitat analysis and clinical data effectively improved the diagnostic efficacy of differentiating borderline from malignant ovarian tumors. The diagnostic efficacy of the habitat subregion (H1) dominated by solid components and the habitat overall region was superior to that of the habitat subregion dominated by cystic components.

Vascular tumours and malformations encompass infantile hemangiomas (IHs) and genetically driven vascular malformations with distinct natural histories and therapeutic vulnerabilities. The discovery that the non-selective beta-blocker propranolol induces rapid regression of proliferating IHs established the first widely adopted systemic pharmacologic therapy in vascular anomaly care and provided a clinical proof-of-concept that targeting lesion-specific endothelial biology can alter disease course. In parallel, recurrent somatic variants affecting PI3K/AKT/mTOR (e.g., PIK3CA, TEK/TIE2, AKT1) and RAS/MAPK (e.g., KRAS, NRAS) signalling have reframed many malformations as mosaic disorders amenable to targeted inhibition with agents such as sirolimus, alpelisib, AKT inhibitors and MEK inhibitors. This review synthesizes translational mechanisms, clinical evidence and safety considerations for beta-blockers and emerging targeted therapies, emphasizing lesion phenotype, timing of intervention and molecular stratification as determinants of response. We highlight current limitations, including toxicity, durability and pathway escape, and outline future directions for precision therapy and genotype-guided trial design in vascular anomalies.

The lncRNA NEAT1 is overexpressed in multiple myeloma (MM) plasma cells and plays a key role in MM pathogenesis. NEAT1 is involved in ceRNA network in several cancers; however, data in MM are virtually absent. This study identified a NEAT1-driven ceRNA network involving 96 miRNAs and 40 target genes, selected as concurrently downregulated in NEAT1-KD AMO1 cells and upregulated in NEAT1-overexpressing AMO1 cells (AMO1-OVX). The co-expression of NEAT1 and the targets was validated in MM patients (GSE116294, GSE13591, GSE6477, CoMMpass), and in NEAT1-KD NCI-H929, LP1, and KMS27 cell lines, showing for all targets a consistent downregulation, resembling that of NEAT1. The functional implication of the ceRNA network was explored by functional enrichment analyses of the 40 targets, identifying 78 significant gene sets, 17 of which were found significantly enriched by GSEA analysis in at least one experimental condition among NEAT1-KD LP1, NCI-H929, and KMS27 cells, AMO1-OVX cells, or the extreme quartiles of NEAT1 expression in the CoMMpass dataset. Noteworthy, the cell cycle gene set was validated in 5 out of 6 conditions tested, suggesting that in MM the impact of NEAT1 upregulation on the cell cycle, experimentally demonstrated in our earlier publications, may be attributable, at least partially, to ceRNA mechanisms.

Pheochromocytomas and Paragangliomas (PPGL) are rare neuroendocrine tumors with favorable prognosis, although a significant subset (20-25%) progress to metastasis, worsening patient prognosis. For metastatic cases, pharmacological interventions become essential, yet most tumors show poor response to treatment. While clinical trials are ongoing, there is no established treatment for metastatic PPGL. Like other neuroendocrine tumors, PPGL exhibit high membrane expression of somatostatin receptors, and despite Peptide Receptor Radionuclide Therapy, PRRT, strategies have successfully been implemented, trials with cold somatostatin analogs were abandoned prematurely due to inconsistent results. To investigate this issue and identify potential therapeutic tools, we widely profiled somatostatin receptors expression in PPGL and conducted a comprehensive functional screening on wild-type and SDHB knockdown PPGL cell lines of native and synthetic somatostatin analogs. Results revealed that pheochromocytomas and paragangliomas similarly display a predominant SSTR2 and SSTR1 expression regardless of molecular cluster. Treatment with somatostatin, cortistatin, octreotide or pasireotide did not exert clear antitumoral effects on model cell lines. Notably, the selective SST2 agonist BIM-23120 significantly reduced cell proliferation and induced apoptosis in an SST2-dependent manner, but only in SDHB knocked-down PPGL cells. Indeed, only SDHB KD cells showed stronger membrane-enriched SST2 and clear receptor internalization upon BIM-23120 treatment. Molecular analysis revealed a generalized dephosphorylation affecting key proliferation, growth and cell survival pathways in response to BIM-23120 (unlike when treating with octreotide). Altogether, our results provide novel information on the status of the somatostatin system in PPGL and identify new potential therapeutic tools selectively targeting somatostatin receptors on this refractory tumor.

This study investigated patients whose initial diagnosis was de novo Stage IV gastric cancer, a population with extremely poor prognosis and limited evidence regarding how longitudinal nutritional changes evolve over time in advanced disease. We examined the trajectories of hemoglobin (Hgb), body mass index (BMI), and the prognostic nutritional index (PNI) as well as descriptively explored differences in nutritional trajectories between survival-defined groups based on one-year survival.