IntroductionDysregulated epidermal growth factor receptor (EGFR) signaling is a key mechanism driving cancer progression and metastasis. Owing to its frequent overexpression in pancreatic cancer (PCa), EGFR has become a desirable molecular target for targeted therapies. XYZ-I-73 (N-(5-fluoro-2-oxo-1-(tetrahydrofuran-2-yl)-1,2-dihydropyrimidin-4-yl) dodecanamide), a structural analog of 5-fluorouracil (5-FU), has been previously synthesized and shown to exhibit cytotoxicity against PCa cells.MethodsXYZ-I-73 was entrapped in liposomes via thin-film hydration and subsequently conjugated to EGFR antibodies to produce an immunoliposome formulation- Ab-XYZ-I-73LnP (where 'Ab' denotes antibody-conjugated and 'LnP' denotes liposomal nanoparticle). In vitro efficacy was assessed by measuring cell viability and apoptosis in MiaPaCa-2 and PANC-1 cells, while pharmacokinetics and antitumor efficacy were determined in a cell line-derived xenograft (CDX) mouse model.ResultsAb-XYZ-I-73LnP exhibited a mean particle size of 143nm ± 2.3, PDI (0.37), and zeta potential -46.2 ± 1.3mV. In MiaPaCa-2 cells, Ab-XYZ-I-73LnP showed remarkably higher cytotoxicity than 5-FU in both 2D (IC₅₀ = 2.5 ± 0.9μM vs 13.2 ± 1.1μM) and 3D cultures (IC₅₀ = 8.1 ± 1.1μM vs 26.7 ± 1.1 μM). Similarly, in PANC-1 cells, Ab-XYZ-I-73LnP showed lower IC₅₀ values compared to 5-FU;2D (IC₅₀ = 2.9 ±1.1 μM vs 20.4±1.2 μM), 3D (IC₅₀ = 12.9 ± 0.6μΜ vs 37.1±0.9 μM). Pharmacokinetic analysis revealed a prolonged half-life for Ab-XYZ-I-73LnP compared with free 5-FU (t1/2 = 1.62 ± 0.03 h vs 0.49 ± 0.01 h, p < 0.001). There was about a 2-fold increase in the area under the curve (AUC) for Ab-XYZ-I-73LnP compared to 5-FU (AUC= 0.32 ± 0.04µg/(L*hr) vs 0.15 ± 0.02µg/(L*hr), p<0.01).ConclusionOverall, the study supports the formulation of an immunoliposome of modified 5-FU, which may significantly enhance drug bioavailability and therapeutic potential for the treatment of PCa.

The mechanisms underlying the interactions between disseminated tumor cells (DTCs) and their tissue microenvironment during metastatic colonization are currently poorly understood. We integrated multimodal single-cell and spatial profiling from liver cancer mouse models and human metastases to track the spatiotemporal dynamics of DTCs and their microenvironments from single-cell seeding to overt lung metastasis. We identified a residual population of quiescent Phgdh^high DTCs that survived initial innate immune clearance and became transiently enriched in micrometastases. These cells shaped an immune-scarce microenvironment through PHGDH-dependent, H3K27me3-mediated epigenetic silencing of chemokine transcription, thereby promoting metastatic expansion. Cx3cr1^high interstitial macrophages were also transiently enriched before DTC expansion, creating an immune-privileged niche for metastatic outgrowth by recruiting immunosuppressive cells. Inactivating the PHGDH-H3K27me3 axis in DTCs or depleting interstitial macrophages restored immune surveillance and inhibited metastatic colonization. These findings provide insights into the development of micrometastasis-targeting regimens.

Lymphangioleiomyomatosis (LAM) is a rare disease of unknown etiology that occurs almost exclusively in women, primarily of reproductive age. This disease is characterized by smooth muscle cell proliferation, most commonly in the lungs. However, cases of extrapulmonary LAM have been reported, such as in the lymph nodes of mediastinum, abdominal cavity, and retroperitoneum. The clinical manifestations of pelvic lymph node LAM are subtle manifesting as symptoms of compression due to a large tumor mass but more often diagnosed incidentally in lymph node specimens removed during gynecologic oncology surgeries. This article provides literature data and our own observation of lymph node LAM in a patient with metastatic endometrial cancer.

The paper presents a clinical case of appendiceal mucinous adenocarcinoma with invasion into the right ovary, imitating an ovarian tumor. The primary tumor was diagnosed only after a pathological evaluation of the surgical material with differential immunohistochemical assay after laparotomy and removal of the ovarian tumor and appendectomy. Difficulties in establishing an accurate diagnosis were caused by extensive invasion of the appendiceal tumor into the ovary. This disease requires increased oncological alertness and a clear algorithm for differential diagnosis of mucinous tumors of the appendix and ovary.

To determine the molecular genetic characteristics of the epithelial neoplasia of extrahepatic bile ducts (EHD) depending on the degree of epithelial dysplasia in order to identify mutations that facilitate their differential diagnosis.

The study included 44 EHD biopsies containing epithelial neoplasms and cholangiocarcinoma. All samples underwent massive parallel sequencing of DNA isolated from 10-μm-thick histological sections. Mutations of categories I-III of clinical significance were considered. Statistical analysis of the obtained data utilized a two-tailed Pearson χ² test with Holm's correction for multiple comparisons (p<0.045).

The most frequent mutations in epithelial neoplasia of the EHD were identified: MYC, KRAS, PIK3CA, CDKN2A, ERBB2, KIT 6, TP53 6, FBXW7, POLE and TERT. The highest proportion of mutations was in biliary intraepithelial neoplasia and cholangiocarcinoma. Among epithelial neoplasia and cholangiocarcinoma, mutations in KRAS, POLE and TERT differed significantly. KRAS (p<0.045) - BilIN LG and BilIN HG, IPNB HG and cholangiocarcinoma; POLE (p<0.045) - BilIN LG and cholangiocarcinoma; TERT (p<0.045) - BilIN LG and cholangiocarcinoma. Specificity and sensitivity indicators for KRAS were 28 and 50%; POLE - 35 and 100%; TERT - 100 and 100%.

Mutations have been identified that should be considered in the differential diagnosis of the degree of epithelial dysplasia and the types of epithelial neoplasia of the extrahepatic bile ducts.

To study the morphological patterns of immune-related cutaneous lesions (irCLs) that occur during antitumor immunotherapy in cancer patients.

The study included 48 patients with the following nosology: malignant neoplasms of the skin and soft tissues - 20 patients (41.7%), malignant neoplasms of the genitourinary system - 13 (27%), malignant neoplasms of the lungs and bronchi - 9 (18.8%), malignant neoplasms of the upper respiratory tract - 5 (10.4%), malignant neoplasms of the gastrointestinal tract - 1 (2.1%), with immune-mediated skin lesions during treatment with pembrolizumab - 25 (52.1%), nivolumab - 18 (37.5%), prolgolimab - 4 (8.3%), avelumab - 1 (2.1%).

Among the irCLs in the study cohort, lichenoid - 14 (29.2%) cases and psoriasiform - 11 cases (22.9%) were predominant, while other morphological variants were significantly less common. IrCL morphologically mimic classic dermatoses, but have distinctive features indicating their drug-induced, immune-related nature.

The study demonstrated that irCLs are clinically significant complications of PD-1/PD-L1 inhibitor therapy. Histological analysis confirmed their immunoinflammatory nature and revealed characteristic morphological changes, emphasizing the importance of routine skin biopsies for optimal patient management.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, driven by late-stage diagnosis, metastatic progression, and therapeutic resistance. Src homology region 2 domain-containing phosphatase 2 (SHP2) has emerged as a critical regulator of oncogenic signaling in gastric tumorigenesis, yet its therapeutic targeting remains underexplored. In this study, we evaluated the anti-cancer efficacy of NSC 57774, a novel SHP2 inhibitor, using integrated bioinformatics and functional assays in AGS gastric cancer cells. Analysis of The Cancer Genome Atlas (TCGA) and UALCAN datasets revealed marked upregulation of SHP2 and multiple receptor tyrosine kinases in gastric cancer tissues. NSC 57774 potently inhibited cell proliferation and migration, demonstrating selective cytotoxicity towards cancer cells over non-cancerous fibroblasts. Mechanistically, NSC 57774 disrupted key oncogenic pathways including MAPK/ERK, AKT and STAT3 in a concentration- and time-dependent manner, with higher doses achieving more sustained pathway suppression. NSC 57774 suppressed NF-κB inflammatory signaling at early timepoints and induced cleaved caspase-3 across all treatment groups at 72 hours, indicative of pro-apoptotic activity. A paradoxical late-phase increase in phospho-p38 was observed at 72 hours, consistent with a compensatory pro-apoptotic stress response. Comparative analysis revealed that NSC 57774 outperformed the commercial SHP2 inhibitor NSC 87877 and doxorubicin in reducing viability and migration of gastric cancer cells. Collectively, these findings position NSC 57774 as a promising candidate for targeted gastric cancer therapy, capable of disrupting multiple signaling pathways involved in tumor progression, metastasis, and inflammation, warranting further preclinical and clinical investigation.

Cardiothoracic involvement by obstetric and gynecologic pathologic conditions creates a broad spectrum of clinical and radiologic manifestations, ranging from mild to critical. The authors describe the unique and often unrecognized or unexpected imaging manifestations of obstetric and gynecologic conditions in the chest. Pregnant, peripartum, and postpartum patients experience varied disorders, including eclampsia/preeclampsia, pulmonary edema, pneumonia, aspiration, acute respiratory distress syndrome, thromboembolism, other forms of embolic disease, cardiomyopathy, and metastatic gestational trophoblastic disease. Appropriate methods of imaging pregnant patients are also discussed. Gynecologic malignancies develop characteristic patterns of thoracic involvement related to the pathways of tumor spread and underlying histopathologic tumor features. Laboratory biomarkers add diagnostic value to imaging interpretation in this setting. Benign forms of gynecologic disease manifest in the chest as Meigs syndrome, thoracic endometriosis syndrome, and intravascular or metastasizing leiomyomatosis. To facilitate accurate and timely radiologic diagnosis, the authors provide a comprehensive overview of cardiothoracic imaging findings associated with benign and malignant obstetric and gynecologic conditions. ^©RSNA, 2026 Supplemental material is available for this article.

Mirvetuximab soravtansine is an antibody-drug conjugate targeting folate receptor alpha (FRα), which is used in the treatment of platinum-resistant ovarian cancer. Its administration is associated with a distinct spectrum of ocular adverse events, representing a clinically relevant limitation of therapy. The most common manifestations include keratopathy, blurred vision, and dry eye symptoms. These effects are generally reversible and manageable upon appropriate ophthalmologic monitoring. This review summarizes the current knowledge regarding the mechanisms, clinical presentation, incidence, prevention, and management of mirvetuximab-associated ocular toxicity.

The treatment of non-small cell lung cancer (NSCLC) has challenges such as drug resistance and recurrence. Concurrently, the induction of apoptosis and ferroptosis is a promising therapeutic strategy. This study aimed to investigate whether the natural product, verbascoside, induces apoptosis and ferroptosis in NSCLC cells by targeting BCAT2.

Bioinformatic analysis was used to predict the potential targets of verbascosides. Stable cell lines with BCAT2 knockdown and overexpression were constructed. The effects of verbascoside on NSCLC were evaluated in vitro and using a mouse xenograft model.

Bioinformatics screening and molecular docking identified BCAT2 as a potential target of verbascoside, with a significantly stronger binding energy (-7.8 kcal/mol) than another candidate, PARP1. In vitro and in vivo experiments confirmed that BCAT2 knockdown significantly inhibited NSCLC cell viability, induced apoptosis and ferroptosis, and induced mitochondrial damage. Conversely, BCAT2 overexpression produced opposite effects. Verbascoside treatment inhibited BCAT2 expression in a concentration-dependent manner, recapitulating the apoptotic, ferroptotic, and mitochondrial damage phenotypes induced by BCAT2 knockdown; however, BCAT2 overexpression significantly reversed these effects of verbascoside. In an animal model, treatment with verbascoside significantly suppressed tumor growth and activated apoptosis and ferroptosis in tumor tissues by downregulating BCAT2.

Verbascoside can induce apoptosis and ferroptosis in NSCLC by directly targeting and inhibiting BCAT2, leading to mitochondrial dysfunction. This finding not only reveals BCAT2 as a novel target of verbascoside but also confirms its ability to induce apoptosis and ferroptosis in NSCLC cells.