Refractory and recurrent uterine fibroids present complex therapeutic challenges, particularly in patients who desire fertility preservation. Clinical management must balance multiple competing risks: preserving reproductive potential, preventing oestrogen-stimulated regrowth during assisted reproduction, and avoiding complications from repeated surgical interventions.

We report a challenging case of a woman with multiple recurrent refractory uterine fibroids and associated infertility. The patient underwent two prior open myomectomies followed by four sessions of high-intensity focused ultrasonography. Due to inadequate response, subsequent combination therapy included ultrasound-guided absolute ethanol injection into the residual perfused fibroid tissue and three months of gonadotropin-releasing hormone agonist administration. Pregnancy was ultimately achieved through in vitro fertilization embryo transfer.

Following the combined treatment approach, the patient successfully conceived and delivered a healthy newborn.

This case suggests that for patients with difficult-to-treat, recurrent uterine fibroids, a multimodal strategy combining serial high-intensity focused ultrasound procedures with adjuvant gonadotropin-releasing hormone agonist therapy may facilitate favorable reproductive outcomes. Although the evidence continues to evolve, this successful live birth offers clinical support for the use of this integrated approach in selected cases.

The role of a cancer genetic counselor includes communication about emotions, thoughts, and decision-making related to prophylactic surgery. No prior study has fully evaluated the preferences of young adults who are BRCA1, BRCA2 (BRCA1/2), or PALB2 positive and their communication preferences on discussing prophylactic surgery in a genetic counseling session. We addressed this through semi-structured interviews with 13 individuals who were assigned female sex at birth, aged 18-30 during the time of genetic counseling, had seen a genetic counselor in the past 7 years, and tested positive for a BRCA1/2 or PALB2 pathogenic or likely pathogenic variant. Coding by two researchers and reflexive thematic analysis by three researchers was conducted to explore preferences of this population. Five major themes were constructed in analysis: (1) care personalized for life stage and identity; (2) personal and community factors impacting decision-making; (3) communication about gene-positive medical management; (4) healthcare system concerns; and (5) preferences for genetic counselor post-test counseling and follow-up. Young adult participants discussed that life-stage considerations such as body image, sexuality, and childbearing were important factors in their emotions and decision-making around prophylactic surgery, differing from previous literature on older populations. Participants desired more follow-up, better support and education around practical and emotional considerations for prophylactic surgery, and acknowledgment of personal and community factors that impacted them. Genetic counselors can personalize each visit to the patient and their needs by extensively contracting and bringing up topics that may be relevant and adjusting based on their preferences and values.

<b>Introduction:</b> Although genetic mutations have been reported in salivary duct carcinoma (SDC), no scientifically validated targeted therapies are currently available. Moreover, cancer genomic profiling tests remain underutilized in clinical practice. These issues highlight the urgent need to elucidate the genomic landscape of SDC and its potential therapeutic relevance. <br><br><b>Aim:</b> This study aimed to characterize the mutational profile of recurrent and/or metastatic SDC. <br><br><b>Materials and methods:</b> Data were analyzed for 207 consecutive patients with SDC registered at the Japan National Cancer Center, Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 2019 and October 2025. Genetic mutations were determined by next-generation sequencing. Survival of patients was determined by the log-rank test and the Cox proportional hazards model. <br><br><b>Results:</b> The top 10 mutations in SDC were <i>TP53</i> (74.4%), <i>ERBB2</i> (52.2%), <i>NF1</i> (32.4%), <i>CDK12</i> (29.0%), <i>PIK3CA</i> (28.0%), <i>NOTCH3</i> (19.8%), <i>LTK</i> (18.4%), <i>CDKN2A</i> (18.4%), <i>BRCA2</i> (16.9%), <i>SPEN</i> (16.9%), with 17.1 7.2 (mean standard error of the mean [SEM]) mutations/individual. <i>TP53</i> mutations (p = 0.005707) were associated with a significantly worse prognosis, as determined by log-rank test. The hazard ratios for cases with this mutation was 2.6390 (95% CI, 1.2180-5.720, p = 0.0139) for <i>TP53</i>. <br><br><b>Conclusions:</b> This study delineated the mutational spectrum of recurrent and/or metastatic SDC. Even in advanced disease, prognostically relevant mutations were identified, emphasizing the clinical importance of cancer genomic profiling tests.

Leptomeningeal disease (LMD) or leptomeningeal metastases (LM) occurs when tumor cells invade the leptomeningeal and cerebrospinal fluid (CSF) space. Melanoma is the most common cancer causing LMD (M-LMD). Its biology and pathophysiology are very poorly understood. Research efforts are being made to explore the mechanisms underlying the immune landscape and antitumor response in LMD. The significant advances in immunocellular and targeted therapies in unresectable or metastatic melanoma in the last decade have not translated to patients with LMD and the prognosis for these patients remains dismal. While several reviews in LMD have provided an overview including challenges in diagnosis and treatment, herein we highlight evidence-based findings with a focus on immunocellular and radiation therapies, as well as the challenges that we need to overcome to help breach the existing gap in research and treatments in M-LMD. This could potentially guide additional research avenues and a better understanding of the needs and challenges of M-LMD to find novel therapies and improve patient survival.

Omics' technologies have enabled clinicians to gain previously unprecedented insights into the molecular complexity and clinical heterogeneity of triple-negative breast cancer (TNBC). Increasingly it is being realized that TNBC does not respond well to current targeted therapies. This study aims to explore the antiproliferative effects and cancer regulatory mechanisms which underlie the drug resistance and aggressiveness of TNBC cells. Cryptocaryone (CPC) derived from Cryptocarya concinna demonstrated antiproliferative responses to TNBC cells (HCC1937 and MDA-MB-231), while normal breast cells (H184B5F5/M10) exhibited low cytotoxicity. In an in vivo assessment, CPC effectively reduced tumor growth in the MDA-MB-231 xenografted mouse model without significantly affecting body weight. Mechanistically, CPC triggered apoptosis, as indicated by an increase in sub-G1 and annexin V, as well as activated caspase 3 and 8. CPC also induced substantial oxidative stress by generating reactive oxygen species, mitochondrial superoxide, and membrane depolarization. CPC also induced oxidative DNA damage, as evidenced by the presence of γH2AX and 8-hydroxy-2-deoxyguanosine, in TNBC cells. All these CPC-induced changes were more pronounced in TNBC cells than normal cells. JNK and p38 MAPK inhibitors attenuate CPC-induced antiproliferation in TNBC cells. CPC upregulates phosphorylated JNK and p38 in TNBC cells. N-acetylcysteine pretreatment confirmed that oxidative stress plays a vital role in enhancing the antiproliferation, apoptosis, and DNA damage in TNBC cells. Moreover, the CPC-upregulated apoptosis and caspase 3/8 activations in TNBC cells were inhibited by JNK and p38 inhibitors. The impact of ERK activation on antiproliferation and apoptosis was evident in MDA-MB-231 cells, but not in HCC1937 cells. In conclusion, CPC demonstrated antiproliferative effects on TNBC cells through apoptosis and DNA damage induced by oxidative stress and MAPK activation, while showing drug safety in normal cells and breast cancer mouse model.

Breast cancer is the most common cancer in females worldwide, and the incidence rate in China has been increasing in recent decades. The treatment of breast cancer with cyclophosphamide (CTX) is one of the cornerstones of combination chemotherapy. However, the mechanisms underlying the anti-tumor effect of CTX is not fully understood. CCK8 assay was employed to detect the IC50 value and viability of breast cancer cell lines (MCF-7 and 4T1). Cell morphology was observed. Tunel assay was carried out to determine cell apoptosis. The content of iron level (Fe²⁺), malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) was assessed to measure the ferroptosis level. Western blot measured the expression of ETNK1, and autophagy-related proteins (Beclin1 and LC3). The mechanism in vivo was verified in the nude mice model transplanted with MCF7 cells. CTX inhibited cell proliferation, promoted cell apoptosis and ferroptosis in vitro. Inhibition of autophagy could suppress CTX-induced ferroptosis. CTX treatment could increase ETNK1 expression. Downregulation of ETNK1 could reverse the impacts of CTX on cell survival, ferroptosis, and autophagy both in vitro and in vivo. CTX-induced iron death dependent on autophagy in breast cancer cells by promoting the expression of ETNK1.

Cancer stem cells (CSCs) represent a dynamic, therapy-refractory subpopulation that fuels tumor initiation, metastasis, and relapse through remarkable self-renewal capacity and phenotypic plasticity. Extensive evidence has established that hypoxia-inducible factors (HIFs), especially HIF-1α and HIF-2α, are key regulators of CSC behavior within the hypoxic tumor microenvironment (TME) across diverse malignancies, including breast cancer, glioblastoma, and colorectal carcinoma. Under hypoxic conditions, HIFs stabilization orchestrates stemness maintenance, epithelial-mesenchymal transition (EMT), immune evasion, and metabolic reprogramming. Concurrently, HIF activity upregulates efflux transporters and anti-apoptotic genes, thereby contributing to resistance against chemotherapy and radiotherapy. This review integrates recent advances in HIF-CSC crosstalk, with particular emphasis on interactions with core pluripotency networks (Oct4, Sox2, Nanog), therapy-induced CSC enrichment, and hypoxia-driven immune suppression. We further highlight current limitations and prospects of HIF-targeted strategies, including isoform-specific inhibitors and combination regimens. By addressing existing knowledge gaps, this work provides a comprehensive framework to guide the development of next-generation therapies aimed at durable CSC eradication and improved clinical outcomes in hypoxia-driven cancers.

Primary liver cancer (PLC), mainly hepatocellular carcinoma (HCC), remains a leading global cause of cancer mortality. Metabolic dysregulation is a hallmark of HCC progression. Sophoricoside (SOP), a flavonoid glycoside from Sophora japonica, exhibits anti-inflammatory and metabolic regulatory activities, yet its role in liver cancer is unclear. Here, we investigated the antitumor effects and underlying mechanisms of SOP in HCC. Huh7 and HepG2 cells were treated with increasing SOP concentrations to assess proliferation, migration, and invasion using CCK-8, colony formation, wound-healing, and Transwell assays. Transcriptomic profiling (RNA-seq) and pathway enrichment analyses were conducted, followed by RT-qPCR and Western blot validation. In vivo efficacy was evaluated in Huh7 xenografts (160 mg/kg, daily for 27 days). SOP inhibited proliferation in a dose-dependent manner (IC₅₀ ≈ 320 μM), reducing clonogenicity by ~65% (p < 0.01) and suppressing migration and invasion by 60%-70%. These effects correlated with decreased PCNA, Cyclin D1, and N-cadherin, and upregulated E-cadherin. RNA-seq revealed 1263 differentially expressed genes, with AMPK pathway activation and repression of G2M, E2F, and MYC signaling. SOP increased AMPK phosphorylation (Thr172; +2.5-fold at 300 μM) without affecting total AMPK. In vivo, SOP reduced tumor volume by ~60% and Ki67 expression while sustaining AMPK activation. Co-treatment with the AMPK inhibitor compound C abrogated these effects, confirming AMPK dependence. Collectively, SOP functions as a natural AMPK agonist that reprograms tumor metabolism and suppresses oncogenic signaling, highlighting its promise as a low-toxicity therapeutic candidate for liver cancer.

Although numerous biological properties of curcumin, a bioactive polyphenol from the rhizome of turmeric (Curcuma longa), have been documented, its poor bioavailability limits clinical application. Therefore, identifying new analogs with improved pharmacokinetics and pharmacological properties is essential. Given that curcumin and its related compounds are known to inhibit cancer cell progression and metastasis through nuclear factor-kappaB (NF-κB) signaling inhibition, we investigated 58 newly synthesized, structurally diverse monocarbonyl curcumin analogs. Their inhibitory effects on intrinsic NF-κB activity were assessed in breast cancer cells using the 4T1 cell line expressing a luciferase NF-κB reporter. Among the 58 monocarbonyl curcumin analogs, 3,5-bis(2-ethoxybenzylidene)piperidin-4-one (E145) exhibited potent inhibition of NF-κB activity in 4T1 breast cancer cells. Based on the structure-activity relationship analysis, the central heterocyclic monocarbonyl linker structure of E145 contributed to its increased potency in NF-κB inhibition.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. The identification of effective molecular targets is crucial for advancing precision medicine and prognostic strategies. This study aims to uncover key CRC biomarkers through integrative bioinformatics analyses, providing mechanistic insights for therapeutic development.

We analyzed three CRC datasets from the Gene Expression Omnibus (GEO) database. Expression quantitative trait loci (eQTL) analysis was performed to identify instrumental variables (IVs), which were subsequently used in Mendelian Randomization (MR) analysis with CRC Genome-Wide Association Study (GWAS) data. MR-associated genes were intersected with differentially expressed genes (DEGs) to screen disease-related key genes. Functional enrichment analyses were conducted using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Additionally, immune cell infiltration and gene-immune correlation analyses were performed. Finally, validation was performed using independent GEO, The Cancer Genome Atlas (TCGA) datasets, summary data-based Mendelian randomization (SMR) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in CRC cell lines.

A total of 776 upregulated and 981 downregulated DEGs were identified. Nine key genes were prioritized: ATP13A4, CD1C, METTL7A, SLC18A1, CREB5, CXCR1, GZMB, HECW2, and TEAD2, predominantly involved in cytokine receptor interaction pathways. CIBERSORT analysis revealed increased activated CD4+ memory T cells and M0 macrophages, alongside decreased plasma cells and natural killer (NK) cells in CRC. Key genes demonstrated significant correlation with immune cell subsets (e.g., neutrophils, mast cells), highlighting their role in CRC immunobiology. Validation via SMR and qRT-PCR assays demonstrated significant dysregulation of four target genes (CXCR1, HECW2, ATP13A4) (P < 0.05).

This study suggests that CXCR1, HECW2, and ATP13A4 may be involved in CRC development, providing a reference for targeted and immunotherapy research.