To investigate the effect of Interstitial photodynamic therapy (IPDT) on transplanted tumors of human lung adenocarcinoma A549 cells in nude mice. Twenty-four models of nude mice bearing A549 transplanted tumors were established, which were randomly and equally divided into four groups: the control group, the photosensitizer group, the laser group, and the IPDT group. Each group is treated according to the grouping principle. The tumor volume growth changes in each group were compared. The HE staining was performed to observe the pathomorphological changes of transplanted tumor cells in each group. The TUNEL assay was used to observe the apoptosis induced by IPDT. The qRT-PCR and western blot assays were used to detect the expression levels of Survivin, Caspase-3, Bax, Bcl-2, VEGF and HIF-1α genes in the transplanted tumor tissues. The results showed that the volume of the tumor volume in the IPDT group was noticeably smaller than that in the control, photosensitizer and laser groups, with statistically significant differences (P < 0.05). After HE staining of tumor tissues, there were various necrotic, disordered and foamy cells in the IPDT group. The cells in the other three groups were closely arranged with large hyperchromatic nuclei. The TUNEL assay revealed that more apoptotic cells with brown particles in the nucleus were found in the IPDT group. The results of qRT-PCR and western blot assays showed that compared with the other three groups, the expressions of Survivin, Bcl-2, VEGF, and HIF-1α in the IPDT group were decreased, while the expressions of Caspase-3 and Bax were increased. The differences were statistically significant (P < 0.05). IPDT could significantly inhibit the growth of A549 transplanted tumors in nude mice, which is possibly related to down-regulating the expression of apoptotic factors Survivin and Bcl-2 genes, up-regulating the expression of Caspase-3 and Caspase-9 genes, and down-regulating the expression of angiogenesis-related VEGF and HIF-1α genes.

There is limited evidence supporting the addition of everolimus to endocrine therapy in women with ER-positive/HER2-negative advanced breast cancer disease progression on CDK4/6 inhibitors. We aimed to assess the effectiveness and safety of everolimus in this setting.

EVERGREEN is a multicentre, international, retrospective quasi-experimental study of women with ER-positive/HER2-negative advanced breast cancer who started an immediate next line of endocrine therapy after progression on CDK4/6 inhibitors until 31/12/2022. We compared patients exposed to endocrine therapy plus everolimus in centres where this is the standard-of-care with those treated in centres where endocrine therapy alone is the standard-of-care. The primary endpoint was real-world progression-free survival (rwPFS). Secondary endpoints were time to everolimus failure, time to chemotherapy, and overall survival.

We included 207 women (everolimus n = 150, endocrine therapy alone n = 57), with a median follow-up of 31.8 months. Baseline characteristics were well balanced, except for a higher number of prior lines of therapy in the everolimus cohort. Median rwPFS was 5.0 for patients exposed to everolimus vs 4.3 months for endocrine therapy alone (adjusted hazard ratio 0.68, 95% confidence interval 0.47-0.99). Time to everolimus failure was 4.2 months. There were no statistically significant differences in time to chemotherapy or overall survival. The safety profile was consistent with previous reports.

The addition of everolimus to standard endocrine therapy resulted in a modest clinical benefit for patients with ER-positive/HER2-negative advanced breast cancer candidates for endocrine therapy after CDK4/6 inhibitors. This limited benefit and the toxicity profile warrants careful selection of patients with favourable risk-benefit profile.

Human fibrosarcoma is an aggressive soft tissue malignancy with limited targeted therapies, that prone to rapid metastasis and chemotherapy resistance. Targeting prooxidant pathways represents a promising clinical strategy for the control of fibrosarcoma.

This study evaluated the anti-cancer efficacy and underlying molecular mechanism of 4-chloro-7-Nitrobenzofurazan (NBD) in human fibrosarcoma HT-1080 cells.

Cell viability was determined by MTT assay in HT-1080 cells and normal lung fibroblast (IMR-90). Apoptotic populations and cell cycle progression were determined by flow cytometry using Annexin V-FITC/PI and propidium iodide (PI). Intracellular ROS levels were analyzed using DCFDA. Signaling pathways were assessed through p53/p21 luciferase reporter assay and Western blotting and validated using antioxidant control (Glutathione; GSH) and genetic control (p53 knockout HT-1080).

NBD selectively decreased HT-1080 cell viability (IC₅₀ - 1.83 µM) while sparing the IMR-90 cells (IC₅₀ - 34.02 µM). Flow cytometry analysis revealed concentration-dependent induction of late apoptosis and sub-G₀/G₁ phase DNA fragmentation. Mechanistically, NBD generated intracellular ROS and suppressed the catalase expression, disrupting the redox homeostasis. This oxidative stress induced a biphasic p21 response with potent p53 activation that shifted the cells from cytostatic arrest to apoptosis. Consequently, BCL-2 family proteins shifted toward the pro-apoptotic path, triggering executioner cleaved caspase-3 activation. ROS scavenging by GSH completely blocked p53 upregulation and caspase-3 cleavage, restoring cell viability. Furthermore, p53 KO completely diminished the NBD mediated caspase-3 activation and restored the cell survival.

NBD triggers selective apoptosis in HT-1080 cells via the ROS-induced p53 pathway, highlighting its potential as a redox-targeting therapeutic candidate.

[¹⁷⁷Lu]Lu-PSMA-617 was approved after the VISION trial demonstrated significant benefit in metastatic castration-resistant prostate cancer (mCRPC). This study evaluated outcomes of [¹⁷⁷Lu]Lu-PSMA-617 with or without concurrent Androgen Receptor Pathway Inhibitors (ARPI) in a real-world setting.

We retrospectively analyzed electronic health records of mCRPC patients treated with [¹⁷⁷Lu]Lu-PSMA-617 in routine clinical practice between June 2023 and August 2024. Primary endpoints were overall survival (OS) and PSA50 response; secondary endpoints included PSA-progression-free survival (PSA-PFS), radiographic PFS (rPFS), and percentage PSA change from baseline. Baseline characteristics were compared using Mann-Whitney U and chi-square tests. Survival outcomes were evaluated using Kaplan-Meier and Cox regression analyses.

Among 108 patients, 65 received [¹⁷⁷Lu]Lu-PSMA-617 monotherapy and 43 concurrent ARPI therapy. Baseline characteristics were generally well balanced, with slightly higher hemoglobin and a trend toward lower PSA in the ARPI group. No significant between-group differences were observed for median OS (12.7 vs. 13.5 months; p = 0.96), PSA50 response rate (51.2% vs. 52.3%; p = 0.91), PSA-PFS (6.3 vs. 6.2 months; p = 0.54), or median PSA change from baseline (-39.0% vs. -43.1%; p = 0.24). A non-significant trend in rPFS favored the ARPI group (10.6 vs. 9.8 months; p = 0.057). On multivariable Cox regression, concurrent ARPI use was not independently associated with OS (adjusted HR 1.29; p = 0.33).

In this real-world cohort of ARPI- and taxane-pretreated mCRPC patients, concurrent ARPI use during [¹⁷⁷Lu]Lu-PSMA-617 was not independently associated with improved clinical outcomes. These exploratory findings do not provide evidence to support routine continuation of ARPI beyond progression at the time of radioligand therapy initiation.

Purpose To develop a photoacoustic microscopy (PAM) method for classifying colorectal liver metastasis (CRLM) microvascular networks as angiogenesis-type or vessel co-option-type at different metastatic stages and to evaluate their responses to bevacizumab. Materials and Methods Seventy-two BALB/c nude mice received intrasplenic injections of HCT116-luc or HT29-luc cells to establish CRLM models. PAM was used to visualize CRLM vascular architecture, and its diagnostic accuracy was validated through histopathologic analysis. Intergroup differences in PAM parameters were assessed with one-way analysis of variance or independent-samples t tests. Results PAM differentiated angiogenesis-type from vessel-co-option-type CRLMs according to distinct vascular architectures: Angiogenesis-type CRLMs exhibited lower vessel density (15.66% ± 4.38 vs 31.44% ± 6.95; P < .001) and vessel junction density (1.19 × 10^-3 n/px² ± 0.52 vs 3.12 × 10^-3 n/px² ± 1.11; P = .001) and higher vessel diameter (31.45 µm ± 4.59 vs 13.68 µm ± 1.61; P < .001) and lacunarity (0.294 arbitrary units [au] ± 0.095 vs 0.148 au ± 0.059; P = .003) than vessel co-option-type CRLMs. These differences persisted throughout the 8-week progression period. A 33.3% reduction in vessel density at 3 weeks following bevacizumab treatment was observed in angiogenesis-type CRLMs (untreated, 15.66% ± 4.38 vs treated at 3 weeks, 10.44% ± 4.91; P = .047), with no evidence of a difference in vessel co-option-type CRLMs (untreated, 31.44% ± 6.95 vs treated at 3 weeks, 28.82% ± 3.56; P = .56). Conclusion PAM quantified microvascular signatures differentiating CRLM blood supply patterns and identified vessel co-option-type metastases as resistant to bevacizumab. Keywords: Angiogenesis, Bevacizumab, Colorectal Cancer, Histopathologic Growth Pattern, Liver Metastases, Photoacoustic Imaging, Photoacoustic Microscopy, Vessel Co-Option Supplemental material is available for this article. © RSNA, 2026 See also editorial by Wang and Chen in this issue.

Large cell calcifying Sertoli cell tumor (LCCSCT) is a rare testicular neoplasm, with only a small subset of clinically malignant tumors. We report a diagnostically challenging, clinically and histologically malignant LCCSCT in a 37-year-old man with a misleading initial presentation. The patient initially presented with testicular pain and swelling following trauma and was clinically diagnosed with epididymitis and hydrocele. Despite antibiotic therapy, symptoms progressed to include weight loss, night sweats, fever, diffuse pain, and lymphadenopathy. Computed tomography performed 2 months later demonstrated diffuse lymphadenopathy and enhancement of the right testicular tunica. Fine-needle aspiration and core biopsy of a left supraclavicular lymph node revealed a malignant neoplasm with S100 and SOX10 expression, raising concern for a neural crest-derived tumor. Next-generation sequencing identified a PRKAR1A mutation, further confounding the diagnosis. Extensive imaging failed to identify a primary tumor, and the patient showed no response to chemotherapy. Due to progressive disease and persistent testicular pain, a right orchiectomy was performed, revealing a hydrocele, thickened tunica, and an intratesticular mass. Histologic evaluation demonstrated malignant LCCSCT with cytologic atypia, necrosis, invasive growth, and metastatic disease. A focused literature review identified 22 previously reported clinically malignant LCCSCTs, highlighting variable clinical presentations, frequent S100 positivity, and overlapping immunohistochemical and molecular features that represent important diagnostic pitfalls. This case report emphasizes the need to consider metastatic LCCSCT in the differential diagnosis of metastatic S100/SOX10-positive tumors with PRKAR1A mutations, particularly when a testicular lesion is present or suspected.

Extensive evidence confirms the high effectiveness of human papillomavirus (HPV) vaccines in young girls; however, real-world data on vaccine effectiveness (VE) among women vaccinated at ages 18-45 remain limited, particularly in China, where HPV status at vaccination is often unknown. We conducted a population-based matched test-negative design study using linked cervical cancer screening and immunization records in Shenzhen, China. Cases positive for vaccine-type high-risk HPV (hrHPV) DNA were matched 1:1 with negative controls by age, screening date, household registration, and screening type. VE for at least one dose was estimated using conditional logistic regression and stratified by time since vaccination, vaccine valency, and age at vaccination. Among 7,060 matched pairs, overall VE increased significantly with time since vaccination: 6.4% (95% CI: -3.9% to 15.7%) at <1y, 17.9% (5.5% to 28.7%) at 1-<2y, and 40.2% (29.6% to 49.2%) at ≥2y. Among women vaccinated ≥2y earlier, VE against HPV16/18 was 48.4% (33.7% to 59.8%) for 2-/4-valent vaccines and 54.4% (26.5% to 71.7%) for the 9-valent vaccine. Significant protection at≥2y was observed across all age-at-vaccination groups: 45.7% (25.0% to 60.7%) for ages 18-26, 39.6% (23.5% to 52.4%) for ages 27-35, and 35.5% (12.6% to 52.4%) for ages 36-45. In conclusion, HPV vaccination confers moderate protection against vaccine-type hrHPV DNA positivity among Chinese women vaccinated at ages 18-45. However, as this outcome reflects a single-time-point surrogate virologic endpoint rather than persistent infection or clinical disease, adult women should continue regular cervical cancer screening.

Tumor-derived exosomes mediate intercellular communication in the tumor microenvironment. Epithelial ovarian cancer (EOC) cells secrete exosomes that may regulate bone marrow mesenchymal stem cells (BMSCs), but the underlying mechanisms remain unclear.

This study aimed to investigate whether EOC-derived exosomes regulate BMSCs through the Vascular Endothelial Growth Factor A(VEGF-A)/Mitogen-Activated Protein Kinase(MAPK)/Extracellular Signal-Regulated Kinase(ERK) signaling pathway and to determine the functional consequences of this interaction.

EOC-derived exosomes (EOC-Exos) were isolated by ultracentrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis and Western blot. BMSCs were identified by flow cytometry. BMSCs were divided into control, EOC-Exos and EOC-Exos + ERK inhibitor (U0126) groups. Cell cycle distribution was analyzed by flow cytometry. VEGF-A and MAPK/ERK expression were detected by immunofluorescence and Western blot. VEGF secretion was measured by enzyme-linked immunosorbent assay (ELISA) and VEGF mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR).

EOC-Exos exhibited a typical cup-shaped morphology, ranged from 30 to 150 nm in size and expressed CD9, CD63 and TSG101. BMSCs highly expressed CD90, CD73 and CD105, with low CD45 and CD34. EOC-Exos treatment significantly decreased the proportion of cells in G0/G1 phase (P=0.007) and increased that in S phase (P<0.001), indicating accelerated cell cycle progression. EOC-Exos time-dependently upregulated VEGF-A protein (P<0.05) and ERK phosphorylation (P<0.001). ERK inhibitor U0126 significantly attenuated EOC-Exos-induced VEGF upregulation (P<0.01), VEGF mRNA expression (P<0.01) and S phase increase (P<0.01).

EOC-derived exosomes activate the MAPK/ERK pathway in BMSCs, upregulating VEGF transcription and secretion and accelerating cell cycle progression. ERK inhibition reverses these effects, demonstrating the critical role of this pathway in tumor-stroma interactions.

Head and neck cancer patients undergoing concurrent chemoradiation treatment (CCRT) lose a significant amount of lean soft tissue mass (LSTM) reducing muscle strength and performance. Progressive resistance training (PRT) may mitigate this loss and improve muscle strength and performance. The purpose was to investigate the effects of PRT initiated at CCRT onset on LSTM, muscle strength, and functional performance compared with usual care.

Patients were randomized to 12 weeks of PRT (36 sessions) or usual care with no exercise (control group [CON]). At baseline, after 6 and 12 weeks, 6 and 12 months, Dual-Energy Absorptiometry evaluated total body mass (BM), LSTM, and fat mass (FM); 1 repetition maximum (1RM) chest press and leg press test assessed maximal muscle strength and functional performance (30 seconds chair-rise; 30 seconds arm curls; stair climb) was evaluated. Dietary intake was registered as were Quality of Life questionnaires European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ) C30 and QLQ H&N-35. A sample size of 72 patients (36 per group) was determined a priori with LSTM as the primary endpoint.

Fifty patients were included (required sample size was not met), 25 in each group. From baseline to 12 weeks, patients in the PRT group lost 8.6 ± 1.0 kg BM (10%), 3.4 ± 0.6 kg LSTM (6%), and 5.2 ± 0.8 kg FM (21%). This was not significantly different from the CON group losing 7.4 ± 1.0 kg BM (9%), 3.4 ± 0.6 kg LSTM (6%), and 4.0 ± 0.8 FM (17%). Likewise, 1RM decreased equally in both groups. Chair rise and arm curl performance improved significantly more in PRT compared with in CON (p < 0.05).

In this study PRT initiated at CCRT onset did not attenuate loss of LSTM or muscle strength. However, PRT did result in significantly increased functional performance.

Hepatocellular carcinoma (HCC) remains a major global health burden, characterized by limited therapeutic options and poor prognosis. The present study aimed to evaluate the anticancer potential of leonurine, a natural alkaloid derived from Leonurus japonicus, in HCC. Through an integrated approach of network pharmacology and experimental validation, the PI3K/AKT signaling pathway was identified as a key therapeutic target of leonurine. In vitro experiments demonstrated that leonurine dose‑dependently inhibited HCC cell proliferation, migration and invasion by suppressing PI3K/AKT activation and reversing epithelial‑mesenchymal transition (EMT). In vivo studies confirmed that leonurine significantly attenuated tumor growth and metastasis, with synergistic antitumor effects observed when combined with the PI3K inhibitor LY294002. Collectively, these findings highlight leonurine as a promising candidate for HCC treatment, exerting its efficacy through PI3K/AKT pathway modulation and EMT inhibition. Moreover, the results provide a solid foundation for future clinical investigations and the development of leonurine‑based combination therapies to improve HCC treatment outcomes.