BACKGROUND Hepatocellular carcinoma (HCC) is an aggressive malignancy. Peritoneal metastasis is uncommon but carries a poor prognosis. Diagnosis of HCC with peritoneal metastasis is particularly challenging when alpha-fetoprotein (AFP) levels are normal. This report highlights diagnostic difficulties and the critical role of histopathological confirmation in such atypical presentations. CASE REPORT A 65-year-old man with chronic hepatitis B and a history of lung adenocarcinoma, who had previously undergone radiofrequency ablation and partial hepatectomy for HCC (the primary tumor was histologically confirmed as moderately differentiated HCC with negative AFP immunostaining), presented with recurrent left lower abdominal pain. Laboratory tests showed normal serum AFP but elevated carbohydrate antigen 125 (CA125). Imaging revealed a solitary peritoneal mass without evidence of intrahepatic recurrence. The patient underwent surgical resection. Immunohistochemistry confirmed hepatocellular origin (hepatocyte paraffin 1-positive, arginase-1-positive) and excluded lung adenocarcinoma (thyroid transcription factor-1-negative, napsin A-negative). Importantly, AFP immunohistochemistry findings were negative in the metastatic tumor, consistent with the primary tumor. The Ki-67 proliferation index was 50%. Postoperative recovery was uneventful, and no recurrence was observed at the 3-month follow-up. CONCLUSIONS Normal AFP levels do not exclude recurrent or metastatic HCC. In patients with multiple primary malignancies, diagnosis of new lesions requires careful integration of clinical history, imaging findings, and histopathological evaluation. Surgery may offer both diagnostic and therapeutic value in selected patients, although its long-term benefit remains uncertain.

Extracellular vesicles (EVs/EV) are key mediators of intercellular communication and influence proliferation, migration, and metabolic reprogramming. In breast cancer, EVs released by malignant cells carry bioactive molecules capable of altering the behaviour of surrounding cells. However, it remains uncertain whether these vesicles can directly induce a more aggressive phenotype in benign mammary cells. Melatonin, known for its oncostatic properties, regulates proliferation, metabolism, and signalling pathways associated with tumour progression and may modulate EV-mediated intercellular communication. This study evaluated whether EVs derived from four breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-453 and HCC70), treated or not with melatonin, can modify the phenotype of benign MCF10A cells. EVs were isolated from conditioned media and co-cultured with benign cells. Assays of proliferation, viability, colony formation, migration, lactate production and immunofluorescence were performed to assess EV-mediated effects. EVs derived from malignant cells promoted a more aggressive phenotype in benign cells, as evidenced by increased proliferation, migration, and phenotypic remodelling. In contrast, EVs derived from melatonin-treated malignant cells were associated with reduced lactate production and attenuation of pro-tumoural features. Overall, these findings demonstrate that tumour-derived EVs can induce aggressive traits in benign mammary cells and suggest that melatonin exposure in donor cells modulates EV-mediated effects, attenuating their pro-tumoural influence.

Bladder cancer is the most common malignancy of the urinary tract and is often treated with radical cystectomy with lymph node dissection, followed by a thorough pathological evaluation of the dissected nodes. This is crucial for both accurate prognosis and successful treatment. However, histopathological lymph node examination is labor-intensive and time-consuming.

Skin cutaneous melanoma (SKCM) is a highly aggressive malignancy with a poor prognosis, necessitating the exploration of novel molecular mechanisms driving its progression. CircRNA, which have emerged as critical regulators in cancer biology, have been implicated in various tumorigenic processes. However, their specific roles in SKCM remain inadequately understood.

Brexucabtagene-autoleucel (brexu-cel) is an anti-CD19 chimeric antigen receptor T-cell (CAR-T) product approved for relapsed/refractory Mantle Cell Lymphoma (MCL) after two prior treatment lines, including Bruton tyrosine kinase inhibitors (BTKi). Patients with high-risk (hr) disease-defined by high-intermediate or high-risk MIPI-c, p53 overexpression, or TP53 alterations-have a poor prognosis, underscoring the need for improved first-line strategies. The European Mantle Cell Lymphoma Network therefore designed a phase II trial to investigate the incorporation of brexu-cel into first-line therapy for hr MCL.

Few studies have evaluated the impact of organ-specific tumor microenvironments (TMEs) on clinical outcomes in diffuse large B-cell lymphoma (DLBCL). This study investigated potential molecular markers, the immune cell composition within the TME, and their associations with clinical outcomes in patients with primary intestinal DLBCL (PI-DLBCL). We initially analyzed RNA expression in tumor cells from 19 patients with PI-DLBCL in the experimental cohort. Candidate biomarkers were then assessed in lymphoma tissue from a total of 48 patients in the same cohort, including the 19 with RNA-expression data, and validated in an independent cohort of 29 patients with PI-DLBCL. Associations between these markers and clinicopathological features, event-free survival (EFS), and overall survival (OS) in the two cohorts were analyzed. In the RNA expression panel, CCL5 expression was higher in patients with advanced-stage PI-DLBCL and was associated with inferior EFS and OS. Its principal receptor, CCR5, expressed in approximately one-third of patients, was associated with lower complete response rates to first-line immunochemotherapy: 50% in the experimental cohort and 10% in the validation cohort and correlated with the 7-year worse OS rate in both the experimental (49.8% versus 71.4%, p = 0.082) and validation (0% versus 76.2%, p < 0.001) cohorts. In both the experimental and validation cohorts, CCR5-positive tumors exhibited decreased CD86-positive (M1-like) and increased CD206-positive (M2-like) macrophage infiltration, consistent with an immunosuppressive TME. Multivariate analyses revealed that CCR5 expression was independently associated with worse EFS (p < 0.001) and OS (p = 0.004) in patients with PI-DLBCL (combined experimental and validation cohorts). CCR5 expression indicates a biologically aggressive subtype of PI-DLBCL with poor clinical outcomes and M2 macrophage-dominant immunosuppression.

Lysozyme-induced nephropathy (LyN) is a rare kidney complication associated with chronic myelomonocytic leukemia (CMML). This condition is characterized by distinctive pathological features, including granules within proximal tubular cells that stain positively with periodic acid-Schiff or lysozyme staining, and granular deposits identified as high-electron-density deposits under electron microscopy. Although CMML is the most common cause of LyN, previous reports have suggested that its occurrence may be associated with the myelodysplastic syndrome (MDS). This report describes cases of LyN in a patient with MDS and CMML. Although both the LyN cases, caused by either MDS or CMML, exhibited similar kidney pathological findings, there was a clinical difference in the occurrence of peripheral blood monocytosis. The MDS-induced LyN showed no persistent peripheral blood monocytosis and, when the bone marrow biopsy specimens were stained with lysozyme, numerous positive cells were observed. Thus, hematologic disorders wherein the bone marrow comprises lysozyme-producing cells may induce LyN, even without peripheral blood monocytosis.

According to the literature, in our country, the first choice for the reconstruction of extensive defects after the removal of locally advanced oral tumors is free flap reconstruction, which achieves the best functional outcome. We investigated whether the anterolateral thigh flap, which can be closed primarily at the donor site and is usually indicated for large or complex defects, can be adapted for thin defects, as well.

Daraxonrasib is an orally bioavailable RAS(ON) multi-selective tri-complex inhibitor of the oncogenic mutant and wild-type variants of N, H and KRAS. We previously reported encouraging efficacy in a phase 1/2 clinical trial evaluating daraxonrasib monotherapy at clinically active dose levels in patients with previously treated, RAS mutant metastatic pancreatic adenocarcinoma (PDAC), providing the basis for confirmatory evaluation in the randomized phase 3 RASolute 302 clinical trial. Here we report mechanisms of acquired resistance to daraxonrasib monotherapy observed through targeted sequencing of over 800 genes in paired pretreatment and end of treatment circulating tumor DNA samples from 44 patients in the phase 1/2 clinical trial. Treatment-emergent genomic alterations in the RAS signaling pathway were observed in more than half (26 of 44; 59%) of these patients, including, most notably, mutant KRAS amplifications in one-third (16 of 44; 36%), as well as alterations in receptor tyrosine kinase (RTK) (4 of 44; 9%), MAPK (11 of 44; 25%) and PI3K (4 of 44; 9%) pathways. Notably, no acquired secondary KRAS mutations were observed, distinct from resistance profiles of mutant-selective KRAS G12C(OFF) inhibitors. To corroborate these clinical findings, we found, or mechanistically established, concordant mechanisms of daraxonrasib resistance in human and murine preclinical models of PDAC, including mutant KRAS and MYC amplification and RTK upregulation, with these alterations guiding various combination therapy concepts. Notably, daraxonrasib combined with agents targeting DNA damage response, RTKs or the mutant-selective RAS(ON) G12D inhibitor zoldonrasib averted resistance in preclinical models. Collectively, these results show that most daraxonrasib genomic resistance mechanisms drive reactivation of RAS pathway signaling and guide potential combination strategies in PDAC for further investigation.

Advanced gastric cancer (AGC) poses substantial postoperative challenges that require effective self-management. Although expert patient programs (EPPs) and peer-support approaches have been used in other conditions, an operational program tailored to Chinese surgical patients with AGC has not been established. This study aimed to develop an evidence-informed, disease-adapted EPP focused on postoperative self-efficacy and self-management in this population.

To develop and qualify a physiologically based pharmacokinetic (PBPK) modeling strategy for mithramycin (MTM) and its analog, MTMSA-Trp, with the aim of projecting first-in-human plasma pharmacokinetics and supporting the translational development of MTMSA-Trp for Ewing sarcoma treatment.

Sorafenib remains a systemic treatment option for advanced hepatocellular carcinoma (HCC), but its clinical efficacy is limited by rapid development of adaptive cellular responses that promote cell survival and phenotypic plasticity. Store-operated calcium entry (SOCE) is a key regulator of intracellular calcium signaling and has been implicated in proliferation, apoptosis, migration, and epithelial-mesenchymal plasticity in cancer. This study investigated the association between SOCE and early adaptive responses to sorafenib in Huh7 HCC cells.

Breast cancer is the leading cause of cancer-related death in women worldwide. There is increasing interest in using detailed body composition parameters, such as skeletal muscle mass and adiposity, to better predict treatment response, toxicity, and survival in breast cancer patients receiving neoadjuvant chemotherapy (NAC). This study synthesised current literature on the effect of body composition in breast cancer patients undergoing NAC and identified gaps for future research.

Tumor-specific targeting remains a major obstacle for the development of precision cancer therapies. For several tumors and specifically glioblastoma (GBM), an aggressive brain tumor with poor prognosis, more effective treatments are urgently needed. Recombinant adeno-associated viruses (rAAVs), with their established clinical utility and mutational capsid plasticity, offer a promising platform for targeted delivery. We engineered and evaluated modified AAV capsids derived from the established AAV2 with HSPG-tropism knockdown and two less-characterized, tropism-reduced AAV9 variants. The epidermal growth factor receptor (EGFR), a tumor marker often overexpressed in GBM, was targeted by inserting an affibody (ZEGFR:1907). Also chlorotoxin (CLTX) was inserted, a peptide from scorpion venom reported to bind GBM. Transduction efficiencies were initially assessed with established cell lines (A431, HeLa, U251MG, MCF7). Affibody-displaying capsids exhibited EGFR-dependent transduction, with AAV9-affibody variants surpassing AAV9 wild-type. Several affibody-displaying capsids also transduced patient-derived GBM explants, as confirmed by fluorescence microscopy. These findings highlight the potential of retargeting AAV9 variants and the use of human surgical tissue samples for the initial evaluation of newly designed AAV capsids.

Despite major advances in nanomedicine, therapeutic efficacy remains constrained by unfavorable host responses that influence nanotherapeutic retention, biodistribution, and activity. Biological strategies capable of enhancing nanomedicine performance through modulation of host-response pathways, rather than additional nanoparticle engineering, remain largely unexplored. Herein, we investigated whether a microbial levan produced by Weissella paramesenteroides could potentiate the therapeutic activity of a PEGylated β-cyclodextrin-capped benzimidazole-curcumin nanocomplex (BMPE-Cur) in an Ehrlich ascites carcinoma (EAC)-induced hepatic tumor model. Pharmacokinetic, biochemical, histopathological, angiogenic, immunological, molecular, and computational analyses were performed to evaluate therapeutic efficacy and explore underlying mechanisms. The co-administration of levan increased hepatic BMPE accumulation by 2.3-fold and significantly enhanced the therapeutic efficacy of BMPE-Cur, improving survival to 95.45% compared with 60.66% mortality in untreated tumor-bearing mice. Combination therapy produced 86% inhibition of angiogenesis, markedly suppressed tumor-associated biomarkers, oxidative stress, inflammatory mediators, and immunosuppressive cell populations, and restored hepatic function. These effects were accompanied by reduced expression of components of the TLR2/MyD88/NF-κB pathway, including an 80.05% reduction in MyD88 and a 78.93% reduction in NF-κB, together with 6.59-fold and 7.45-fold increases in FXR and FGF15 expression, respectively. Molecular docking supported potential interactions of BMPE, curcumin, and levan-derived structural motifs with TLR2, while isobolographic analysis demonstrated predominantly synergistic interactions across multiple biological endpoints. These findings support the potential of microbial levan as a promising biological potentiator of nanotherapeutic efficacy, with concurrent enhancement of hepatic nanocomplex retention and coordinated immunometabolic remodeling. More broadly, microbial exopolysaccharides may represent a promising class of host-response modulators, supporting a therapeutic paradigm in which optimizing the biological environment may complement conventional nanocarrier engineering to improve the performance of cancer nanomedicine.

Diabetes Mellitus (DM) is a risk factor for multiple myeloma (MM), but the relationship between diabetic control and risk of progression to MM in patients with monoclonal gammopathy of undetermined significant (MGUS) is unclear. We conducted a retrospective cohort study of US Veterans diagnosed with MGUS from 10/1/1999-12/31/2023 with prior DM. MGUS and MM diagnoses were confirmed using published natural language processing-assisted models. The exposure was time-varying glycated hemoglobin (HbA1c) > 7% during the follow-up (time of MGUS to MM, death, or being censored on 4/15/2025, whichever occurred first). The outcome was time from MGUS to MM. The association was estimated by multivariable-adjusted hazard ratio (aHR) using a Fine-Gray subdistribution hazard model with death as a competing event, adjusted by inverse probability of treatment weighting (IPTW). Among 11,061 patients with DM, HbA1c > 7% was associated with increased progression risk (aHR 1.15; 95% confidence interval [CI] 1.01-1.32). This association was stronger in the subgroups of Type-2 DM (T2DM) with insulin use (n = 7070; aHR 1.46; 95% CI 1.19-1.78) and non-use (n = 3724; aHR 1.42; 95% CI 1.14-1.77) throughout follow-up. For patients with T2DM and MGUS, poorly controlled diabetes may be associated with progression risk to MM. Future studies are needed to confirm this relationship.

Transarterial chemoembolization (TACE) remains a cornerstone therapy for intermediate-to-advanced hepatocellular carcinoma (HCC); however, the optimal embolic platform remains uncertain. This multicenter, retrospective, real-world study (Clinical trial registration number: ChiCTR2500113198) conducted across China compared a novel temperature-sensitive liquid embolic agent, TempSLE-TACE (T-TACE), with conventional drug-eluting bead TACE (D-TACE) in 328 patients with Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC. Following inverse probability of treatment weighting (IPTW), T-TACE achieved significantly superior objective response rates (ORRs) compared with D-TACE according to both RECIST 1.1 criteria (54.11% vs. 27.78%, P < 0.001) and mRECIST criteria (73.56% vs. 54.93%, P = 0.002). T-TACE was additionally associated with significantly prolonged progression-free survival (median PFS: 12.0 vs. 9.0 months; HR = 0.67, P = 0.001) and overall survival (median OS, 24.0 vs. 15.0 months; HR = 0.49, P < 0.001). Moreover, T-TACE demonstrated a favorable safety profile, with lower incidences of hepatic and gastrointestinal toxicities, including any-grade alanine aminotransferase elevation and hyperbilirubinemia. Subgroup analyses further demonstrated consistent OS, PFS, and ORR benefits across major clinical subgroups, with effect sizes remaining significantly favorable in high-risk populations, including advanced portal vein tumor thrombosis type Vp4, baseline AFP > 1000 ng/mL, and PIVKA-II > 2000 mAU/mL. Exploratory histo-molecular and spatial transcriptomic analyses suggested that T-TACE may promote immune microenvironment remodeling through enhanced Th17-cell infiltration and CD8⁺ T-cell activation, whereas incomplete embolization after D-TACE was more frequently associated with residual intermediate-state tumor cells and an immunosuppressive microenvironment. Collectively, these findings provide preliminary evidence supporting T-TACE as a promising real-world therapeutic strategy for intermediate-to-advanced HCC.

Small mothers against decapentaplegic homologue 4 (SMAD4) plays an important role in transforming growth factor (TGF)-β signaling and is associated with various cancers. However, little is known about SMAD4 expression in oral squamous cell carcinoma (OSCC).

Incarceration of the gravid uterus is a rare obstetric complication causing serious maternal and fetal morbidity. This report describes the case of a 43-year-old gravida 3, para 0 woman with a giant uterine fibroid who was diagnosed with an incarcerated gravid uterus at 24 gestational weeks based on transvaginal ultrasonography and magnetic resonance imaging (MRI). The largest fibroid measured 15 cm in maximum diameter and was thought to limit uterine mobility; therefore, conservative management with a planned cesarean delivery was selected. Repeat MRI at 34 weeks unexpectedly demonstrated spontaneous reduction of the incarcerated uterus, with the cervix restored to its normal caudal position. Hence, delivery planning and surgical strategy were revised based on updated anatomical findings. Emergency cesarean delivery was successfully performed at 36 weeks, without recurrence of uterine incarceration. Continuous anatomical reassessment throughout pregnancy, including the third trimester, is essential for optimizing peripartum management and avoiding preventable complications.

Esophagectomy remains the standard of care for T1b esophageal cancer. Guidelines support the use of endoscopic resection (ER) including endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) in carefully selected patients. We compared patients with T1b esophageal cancer who underwent ER or esophagectomy. We searched MEDLINE, EMBASE and CENTRAL from inception to November 2025 for studies comparing esophagectomy and ER for patients with T1b esophageal cancer. We excluded studies if patients received neoadjuvant or adjuvant treatment. Outcomes were 5-year overall survival (OS) and cancer specific survival (CSS), recurrence, and mortality. Meta-analysis (with propensity-matched data when available) was performed, with a subgroup analysis of ESD versus esophagectomy. Ten retrospective studies were identified comprising 2491 patients who underwent ER (n = 890) or esophagectomy (n = 1601). Mean age was 65.7 years with 16.1% female. Six studies grouped EMR and ESD together, three reported ESD alone, one examined EMR only. OS and CSS were available in seven and four studies, respectively. There was no significant difference between esophagectomy and ER regarding 5-year OS (HR 1.26; 95% CI 1.00-1.60; P = 0.05), 5-year CSS (HR 0.65; 95% CI 0.20-2.17; P = 0.49), and 30-day mortality (HR 0.39; 95% CI 0.13-1.16; P = 0.09). Recurrence was 18.1% after esophagectomy and 17.7% after ER. Subgroup analysis showed no difference in OS or mortality. Risk of bias was high in five studies. Available retrospective comparative evidence suggests no clear difference between ER and esophagectomy for patients with T1b esophageal cancer. Randomized controlled trials are needed to reduce patient heterogeneity.