It has been demonstrated that azole antifungal agents can significantly increase the plasma concentration of dasatinib. Therefore, it is recommended to reduce the dasatinib dose to 20 to 40 mg daily for patients receiving voriconazole. However, the safety of coadministering dasatinib and voriconazole remains unclear.

A 49-year-old woman with Philadelphia chromosome-positive acute lymphoblastic leukemia and invasive pulmonary aspergillosis reported dyspnea during therapy with reduced-dose dasatinib and standard-dose voriconazole.

Echocardiography revealed pleural effusion and a mean pulmonary arterial pressure of 40 mm Hg, suggesting pulmonary arterial hypertension.

Dasatinib was discontinued and flumatinib was initiated.

The patient's mean pulmonary arterial pressure was monitored and gradually normalized.

Despite recommendations to reduce the dasatinib dose to 20 to 40 mg daily for patients on voriconazole, the enhanced effect of dasatinib due to voriconazole coadministration may contribute to the development of pulmonary arterial hypertension. Regular echocardiography follow-up is essential for patients concurrently taking azole antifungal agents.

This study aims to investigate the mechanisms by which Huaier extract and autophagy-related factors influence biological functions such as survival and proliferation in cholangiocarcinoma cells. HUCCT1 and QBC939 cholangiocarcinoma cell lines were treated with varying concentrations of Huaier extract (0, 20, 40, and 100 mg/mL) for 24 hours. Cell viability and proliferation were assessed using CCK8 and EdU assays. Flow cytometry was employed to analyze cell cycle distribution and apoptosis. Transwell assays evaluated cell migration and invasion capabilities. Western blotting analyzed protein expression levels of P53, phosphorylated P53, AKT, phosphorylated AKT, ribosomal protein S6, Bcl-2, and Bax in control and high-dose Huaier-treated groups. To explore the role of autophagy in cholangiocarcinoma, gene expression datasets were retrieved from the Gene Expression Omnibus for differential expression analysis. Weighted gene co-expression network analysis identified key gene modules. Protein-protein interaction networks and functional enrichment analyses were conducted, with gene expression heatmaps generated. The comparative toxicogenomics database was used to associate core genes with diseases, while TargetScan predicted microRNAs regulating differentially expressed genes. In HUCCT1 cells, Huaier treatment reduced viability and proliferation in a dose-dependent manner and increased apoptosis. High-dose Huaier significantly decreased Bcl-2, RPS6, AKT, and phosphorylated AKT protein levels. Similarly, in QBC939 cells, Huaier reduced viability, proliferation, migration, and invasion, while promoting apoptosis. High-dose treatment notably decreased RPS6 expression and significantly increased P53 and phosphorylated P53 levels. Bioinformatics analysis identified 4248 differentially expressed genes in cholangiocarcinoma samples. Three core autophagy-related genes (BECN1, ATG7, and DRAM1) were pinpointed. These genes were enriched in autophagy processes, cytoplasmic functions, autophagosome membrane formation, the PI3K-Akt signaling pathway, and apoptosis, with elevated expression in tumor samples. Comparative toxicogenomics database analysis linked these core genes to cholangiocarcinoma, inflammation, necrosis, and proliferation. Huaier extract and autophagy factors Beclin 1, autophagy-related gene 7, and damage-regulated autophagy modulator 1 play significant roles in regulating the growth and proliferation of cholangiocarcinoma cells, highlighting potential therapeutic targets.

ATAD2, a member of the AAA + ATPase family and a known cancer/testicular antigen, has demonstrated oncogenic properties in various cancers. Despite its established role in cancer progression, a comprehensive pan-cancer analysis of its prognostic significance, therapeutic predictive potential, and immunological associations has not been conducted.

We performed a pan-cancer analysis of ATAD2 using data from The Cancer Genome Atlas (TCGA), assessing its expression profiles across different tumor types. We examined its correlations with survival prognosis, clinical outcomes, and cancer-associated signaling pathways. Additionally, we explored the relationship between ATAD2 expression and the tumor immune microenvironment, as well as its predictive value for responses to immunotherapy, targeted therapy, and chemotherapy.

ATAD2 was significantly upregulated in multiple tumor types, and its increased expression was associated with poor prognosis and adverse clinical outcomes. Further analysis revealed that ATAD2 expression was closely linked to cancer-related signaling pathways, tumor mutational burden, and microsatellite instability. Moreover, ATAD2 expression showed strong correlations with immune cell infiltration, immune-related gene expression, and responses to various treatment regimens, including immunotherapy, targeted therapy, and chemotherapy.

ATAD2 is a critical biomarker for poor prognosis and treatment response across a wide range of cancers. Its ability to predict therapeutic responses, particularly for immunotherapy, targeted therapy, and chemotherapy, underscores its clinical significance. Further experimental studies and clinical trials are needed to explore ATAD2's role in cancer progression and its involvement in therapeutic resistance mechanisms.

Ferroptosis, a type of programmed cell death dependent on iron, is characterized by lipid peroxidation of cellular membranes. However, the roles and underlying mechanisms of RNA-binding proteins (RBPs) in modulating ferroptosis in colorectal cancer (CRC) have not been fully explored. In this study, RNA sequencing (RNA-seq) analysis identified ILF3, an RBP, as a crucial regulator of ferroptosis in CRC cells. Our research demonstrated that ILF3 depletion suppressed CRC cell growth and increased sensitivity to ferroptosis. Combined analysis of RNA-seq data and amino acid metabolomics indicated a relationship between ILF3 and glutathione (GSH) synthesis. Further investigation confirmed that ILF3 knockdown reduced GSH synthesis by regulating SLC3A2-mediated cystine uptake. Mechanistically, ILF3 enhances SLC3A2 mRNA stability by interacting with its 3' UTR, leading to increased cystine uptake. Notably, our observations revealed a frequent increase in ILF3 levels in patients with CRC, which was associated with poor prognosis. The elevated ILF3 expression in CRC appears to be partly due to stimulation by tumor necrosis factor alpha (TNF-α) from the tumor inflammatory microenvironment. Additionally, TNF-α was found to decrease sensitivity to ferroptosis by promoting ILF3 expression. Co-immunoprecipitation and liquid chromatography-mass spectrometry assays revealed that the E3 ligase TRIM17 is involved in TNF-α-induced ILF3 upregulation. Specifically, TNF-α inhibited the interaction between ILF3 and TRIM17, thereby protecting ILF3 from ubiquitin-mediated degradation. This resulted in increased ILF3 levels that counteracted ferroptosis. In summary, our study underscores the oncogenic function of ILF3 in CRC and suggests that ILF3 knockdown may serve as a promising therapeutic approach for CRC.

A novel paclitaxel delivery system has the potential to avoid the side effects associated with Cremophor EL and thus enhance therapeutic efficacy. Here, we report the results of a preclinical and phase I clinical study investigating ZSYY001, a nanoparticle formulation of polymeric micellar paclitaxel (PM-paclitaxel).

In preclinical studies, A549, MDA-MB-231, and SKOV3 xenograft tumor models were developed. Various concentrations of ZSYY001 were administered, and tumor growth and body weight were measured. Sprague-Dawley (SD) rats and Beagle dogs were used to evaluate the toxicity. In the phase I study, a dose-escalation study using a 3 + 3 design was conducted in patients with solid tumors. The PM-paclitaxel dose was escalated from 175 mg/m² to 390 mg/m². PM-paclitaxel was intravenously administered over 3 h every 21 days without any premedication. This study was registered with number CTR20210347.

Preclinical studies showed that ZSYY001 significantly inhibited tumor growth without causing weight loss. In the phase I study, all patients were evaluable for toxicity and pharmacokinetic analysis, and 18 patients were evaluable for tumor response. Acute hypersensitivity reactions were not observed. Anemia and hair loss were the most common toxicities. Dose-limiting toxicity events were not observed at any dose levels. Dose escalation to 390 mg/m² did not identify a maximum-tolerated dose. There were two partial responses (11.11%) and seven cases of stable disease (38.89%) among the 18 patients, five of whom had prior exposure to paclitaxel chemotherapy. The paclitaxel area under the curve and peak paclitaxel concentration suggest that PM-paclitaxel does not exhibit linear pharmacokinetics.

ZSYY001 was safe and well tolerated without additional toxicity and exhibited desirable antitumor activity, making it a promising treatment.

CTR20210347.

Cancer stands as a significant global public health challenge, and cancer screening serves as a pivotal strategy for reducing its mortality. Presently, only a limited number of cancer types have appropriate screening methods available. Traditional single-cancer screening approaches are fraught with limitations, including invasiveness, low accuracy, and poor patient compliance. Multi-cancer early detection (MCED) leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA, cell-free RNA, proteins, and metabolites in blood and other bodily fluids. This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage, showcasing immense potential for improving existing cancer screening strategies. This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED, biomarker selection and detection technologies, the criteria for cancer type selection, research design and clinical utility evaluation, as well as implementation pathways. The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED, thereby facilitating the continuous optimization of cancer screening strategies.

To explore the effects of transcutaneous electrical acupoint stimulation (TEAS) at the bilateral acupoints Neiguan (PC6) and Jianshi (PC5) on heart rate variability (HRV) and inflammatory factors in frail elderly patients undergoing laparoscopic colorectal cancer surgery under general anesthesia.

A total of 78 frail elderly patients undergoing elective laparoscopic colorectal cancer surgery were randomized into the TEAS group (39 patients, with 2 patients dropping out) and the control group (39 patients, with 1 patient dropping out). In the TEAS group, TEAS was applied to the bilateral PC6 and PC5 from 30 min before anesthesia induction until the end of the surgery. The control group was connected to an electronic acupuncture instrument at the same acupoints but did not receive electrical stimulation. A short-term Holter electrocardiogram was used to collect HRV parameters in the frequency domain, including low-frequency power (LF), high-frequency power (HF), and the LF/HF ratio. Serum concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) were measured using ELISA. The Quality of Recovery-15 (Qor-15) score was recorded, along with adverse reactions such as postoperative nausea and vomiting (PONV), palpitations, chest tightness, and chest pain.

Compared with 1 d before surgery, LF and HF were significantly decreased (P<0.05), and the LF/HF ratio significantly increased (P<0.05) at 1, 2, and 3 d after surgery in the control group. In the TEAS group, both LF and the LF/HF ratio were significantly decreased (P<0.05) at 1, 2, and 3 d after surgery. Compared with the control group, LF and HF levels were significantly increased (P<0.05), and the LF/HF ratio was significantly decreased (P<0.05) in the TEAS group at 1, 2, and 3 d after surgery. Both groups exhibited increased levels of CRP and IL-6 at 1, 3, and 5 d after surgery compared to 1 d before surgery (P<0.05), with the TEAS group showing lower CRP and IL-6 levels than the control group (P<0.05). Compared to baseline before surgery, the Qor-15 scores of both groups were decreased at 1, 2, and 3 d after surgery (P<0.05), with the TEAS group showing significantly higher Qor-15 scores than those in the control group (P<0.05). The incidence of PONV, palpitations, chest tightness, and chest pain in the TEAS group was lower than that in the control group (P<0.05).

TEAS at the PC6 and PC5 can regulate autonomic nervous function, reduce the early postoperative sympathetic nerve excitation, maintain parasympathetic nerve tension, reduce inflammatory responses, improve the quality of postoperative recovery, and decrease the incidence of postoperative adverse reactions in frail elderly patients after laparoscopic colorectal cancer surgery.

Most breast cancers depend on hormone-stimulated estrogen receptor alpha (ER) activity and are sensitive to ER inhibition. Resistance can arise from activating mutations in the gene encoding ER (ESR1) or from reactivation of downstream targets. Newer ER antagonists occasionally show efficacy but are largely ineffective as single agents in the long term. Here, we show that ER translation is eIF4E/cap-independent yet sensitive to inhibitors of the translation initiation factor eIF4A. EIF4A inhibition reduces the expression of ER and cell cycle regulators such as cyclin D1. This leads to growth suppression in ligand-independent breast cancer models, including those driven by ER mutants and fusion proteins. Efficacy is enhanced by adding the ER degrader, fulvestrant. The combination further lowers ER expression and blocks tumor growth in vitro and in vivo. In an early clinical trial (NCT04092673), the eIF4A inhibitor zotatifin was combined with either fulvestrant or fulvestrant plus CDK4 inhibitor, abemaciclib, in patients with acquired resistance to these agents. Multiple clinical responses including a handful of durable regressions were observed, with little toxicity. Thus, eIF4A inhibition could be useful for treating ER+ breast cancer resistant to other modalities.

Colorectal cancer remains the second leading cause of cancer-related deaths worldwide, highlighting the urgent need for more effective therapies and a deeper understanding of its molecular basis. Drug repurposing has gained traction as a viable strategy to target dysregulated oncogenic pathways. Statins, commonly prescribed for lowering cholesterol, have recently shown potential anti-cancer effects. In this study, we explore how statin treatment influences lipid metabolism, gene expression, and proteomic profiles in colorectal cancer models. Our findings provide direct evidence that statins selectively modulate key components of the Wnt/β-catenin signaling pathway, a major driver of adenoma formation, including members of the special AT-rich sequence-binding (SATB) protein family. We show that statin treatment downregulates SATB1, a known promoter of tumorigenesis in the context of Wnt activation, while simultaneously upregulating SATB2, which plays an opposing role. This reciprocal regulation shifts cellular phenotypes between epithelial and mesenchymal states in 3D spheroid models. Together, these results highlight the therapeutic potential of statins in colorectal cancer and support their consideration in drug repurposing approaches.

The integration of multifunctional components into a single nanoplatform offers significant potential for personalized and minimally invasive therapeutic applications. Herein, we present a facile yet versatile strategy to engineer a near-infrared (NIR) pH- and light-responsive nanomaterial, demonstrating promising efficacy in glioblastoma combination therapy through multimodal synergistic mechanisms.

The FEID nanoplatform was engineered by co-assembling ICG, DOX, and Fe³⁺. Systematic characterization included physicochemical properties (TEM, DLS, UV-vis-NIR spectroscopy, zeta potential measurements, and XPS), photothermal conversion efficiency, Fenton reaction kinetics, PTT-enhanced CDT performance, laser-triggered drug release patterns, and NIR-responsive drug release and dual-modal imaging (fluorescence/MRI) capabilities. Intracellular DOX accumulation and ROS generation were confirmed by confocal laser scanning microscopy and flow cytometry in U87 glioma cells. Hemolysis assay, cytotoxicity profiling against normal 293T and RAW264.7 cells, and H&E staining were applied for biosafety assessment. The synergistic anti-glioblastoma efficacy was systematically evaluated through MTT assays, live/dead cell staining, and apoptosis detection via Annexin V/PI staining. The pharmacokinetic profiles and blood-brain barrier (BBB) permeability of the FEID were analyzed in vivo.

The FEID nanoplatform displayed uniform spherical morphology (78.2 nm average diameter). pH/NIR-triggered release of DOX (chemotherapy) and ICG (PTT), combined with GSH depletion and NIR irradiation, synergistically enhanced Fe²⁺-mediated CDT. This multimodal therapy demonstrated potent cytotoxicity against U87 glioblastoma cells (14.8% cell viability). Furthermore, ICG fluorescence recovery and MRI contrast enabled tumor imaging, while enhanced BBB permeability ensured effective drug delivery for in situ glioma treatment.

In summary, we developed a safe FEID anti-tumor nanoplatform through a simple self-assembly process. This platform demonstrates the potential for controlled drug release and efficient combination therapy.