Sonrotoclax (BGB-11417), a second-generation B-cell lymphoma-2 (BCL-2) inhibitor currently in clinical development, requires comprehensive verification of its biotransformation and disposition profiles in safety species.

The prognosis of metastatic or recurrent hepatocellular carcinoma (HCC) remains poor, and new treatment strategies are warranted. Despite promising preclinical results demonstrating that radiation primes the immune system and produces a synergistic antitumor response for long-term disease control, limited clinical data are available. Therefore, in this study, we investigated the efficacy and safety of combining radiotherapy with immune checkpoint inhibitors (ICIs) for patients with metastatic and recurrent HCC in a real-world setting.

Bone cancer remains a life-threatening malignancy predominantly affecting pediatric and adolescent populations, with tyrosine kinase inhibitors (TKIs) emerging as promising therapeutic agents; however, their clinical utility is limited by poor bioavailability, systemic toxicity, and inadequate tumor targeting. Recent advancements in nanocarrier-based delivery systems have significantly mitigated these limitations by enhancing targeted accumulation of TKIs at tumor sites, reducing off-target effects, and enabling controlled drug release. Various nanocarrier platforms, including liposomes, polymeric nanoparticles, micelles, dendrimers, metal- and metal oxide-based nanoparticles, carbon-based carriers, polymeric implants, and hydroxyapatite-based systems, have been systematically evaluated for their efficacy in delivering TKIs for bone cancer therapy. This review further examines the impact of nanoparticle size on cellular uptake and tumor penetration, with emphasis on liposomal and proteinaceous carriers (albumin-bound and transferrin-conjugated nanoparticles) that optimize tumor selectivity while minimizing systemic toxicity. Inorganic nanocarriers such as gold, silver, and metal oxides also demonstrate potential for multimodal therapeutic and diagnostic applications. Notwithstanding these advances, challenges including drug resistance, toxicity, and regulatory barriers remain, necessitating ongoing efforts to optimize nanocarrier formulations. This comprehensive review provides critical insights into the evolving landscape of nanotechnology-driven TKI delivery strategies aimed at enhancing therapeutic outcomes in bone cancer management.

To investigate the protective effect of ammonium trichloride tellurate (AS101) on doxorubicin induced ovarian function damage in rats.

The rising levels of environmental contamination and oxidative stress disorders have led to a growing demand for multifunctional nanomaterials that possess both biomedical and catalytic importance. CeO2 nanoparticles (NPs) were synthesized using a green solution combustion method involving Ficus carica F. extract, followed by an evaluation of their structural, biological, and photocatalytic properties. XRD confirmed a pure cubic fluorite phase (Fm-3m) with a crystallite size of 11.3 nm, which was also validated through Williamson-Hall and Rietveld refinements (χ2 = 1.9). FTIR spectroscopy revealed strong Ce-O vibrational modes at 955 cm-1, and a bandgap of 3.03 eV was determined through DRS. The SEM/TEM images displayed spherical, agglomerated particles with an average diameter of 13.5 nm. The BET analysis revealed a surface area of 30.081 m2/g, a pore radius of 1.374 nm, and a pore volume of 0.057 cm3/g, confirming the presence of microporosity. The analysis via XPS validated the existence of Ce, O, and C, revealing the coexistence of Ce3+/Ce4+ oxidation states alongside surface hydroxyl species. CeO2 NPs exhibited a dose-dependent redox activity that resulted in a reduction of cell viability to 48.82% at a concentration of 50 µM. H2O2 enhanced LDH release to 223.86%, whereas CeO2 NPs (1-7.5 µM) reduced it to 124.84%, demonstrating redox cycling antioxidant protection. Fluorescence imaging showed dose-dependent duality-antioxidant at low, pro-oxidant at high-consistent with mitochondrial damage and ATP depletion. Furthermore, CeO2 NPs demonstrated a remarkable 94.9% degradation of methylene blue under visible light, indicating their significant potential for both therapeutic and environmental applications.

The highly aggressive primary brain tumor, glioma, presents significant therapeutic challenges, particularly in its diffuse form, which remains resistant to curative treatment even after surgical intervention. Conventional approaches such as surgery, radiotherapy, and chemotherapy often fail to achieve satisfactory outcomes, underscoring the urgent need for more effective targeted therapies. In this study, we have developed novel AKT inhibitors-compounds 3260-0411, V012-5231, and V016-4965. These compounds demonstrate a substantial reduction in both AKT protein and mRNA levels in U251 and T98G glioma cells. Furthermore, our in vitro experiments reveal that these inhibitors effectively suppress AKT1 enzyme activity and induce apoptosis in glioma cells. Molecular dynamics simulations indicate that all three compounds exhibit excellent dynamic stability when bound to AKT; notably V016-4965 demonstrates the highest binding stability among them. Collectively, our findings suggest that compounds 3260-0411, V012-5231, and V016-4965 hold great promise as targeted therapies against AKT for treating glioma-a challenging malignancy with limited management options.

We report a case of a man in his early 70s referred for Grade 2 immune checkpoint inhibitor induced liver injury (ChILI) post nivolumab and ipilimumab for metastatic melanoma. Despite treatment with immunosuppression, the liver enzymes improved but failed to normalise completely. Liver biopsy performed 6 months after diagnosis identified a severe hepatitis with interface and perivenular necroinflammatory activity. Mycophenolate was up-titrated to 1 g twice daily and prednisone 40 mg daily was commenced. Once liver enzymes normalised immunosuppression was then gradually withdrawn, with no recurrent elevation of the liver enzymes. This case demonstrates that there can be an incongruency between liver enzymes an histopathology in ChILI. As in our patient, this can have significant implications in managemen. Furthermore, this case is unique as there are no other reported cases in the literature of chronic ChILI.

Plasma cell-free mRNA provides tissue-specific transcriptional profiling, precisely capturing cardiac damage and immune responses in immunotherapy-induced myocarditis.

Because of the lack of institutional standards, variation in practice for administering chemotherapy and biologics, including clinical trial infusions, was detected. This article describes a National Cancer Institute-designated cancer center's successful education and training of nurses on a new standard method for administering small-volume infusion using the circle priming technique.

Inosine, a bacterial metabolite and agonist of the adenosine A2A receptor, modulates antitumor immunity. However, its precise effects on immune checkpoint inhibitors remain unclear. This study aimed to evaluate the impact of inosine on the efficacy of anti-programmed cell death protein 1 (PD-1) therapy and explore strategies to counteract any potential inhibitory effects. In in vitro co-culture systems, inosine selectively suppressed cancer cell growth without impairing T-cell viability. In a murine subcutaneous tumor model, inosine treatment reduced tumor growth and was associated with elevated interferon-gamma levels in the tumor microenvironment, along with increased infiltration by tumor-infiltrating lymphocytes and enhanced splenic CD4⁺ and CD8⁺ T-cell frequencies. However, the combination of inosine with anti-PD-1 therapy attenuated the antitumor effect and increased cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) expression in splenic T cells compared to levels after anti-PD-1 monotherapy. To overcome this inhibitory effect, we tested whether adding an anti-CTLA-4 antibody could restore antitumor immunity. Notably, the combination of inosine with both anti-PD-1 and anti-CTLA-4 antibodies significantly enhanced antitumor efficacy. These findings suggest that inosine may synergize with dual ICI therapy and represent a promising adjunct to improve immunotherapeutic outcomes.

To investigate the 12-month effectiveness and safety of intravitreal faricimab (IVF) in patients with neovascular age-related macular degeneration (nAMD) resistant to previous anti-VEGF treatment.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with limited treatment options due to its desmoplastic and immunosuppressive tumor microenvironment (TME), which impedes drug delivery and limits T cell infiltration. Immune checkpoint blockade (ICB) has shown poor efficacy in PDAC, partly due to the desmoplastic stroma and low immunogenicity. Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) promotes both fibrosis and immune evasion, making it a compelling target for TME remodeling. Here, we develop a dual-action, programmable immunoprobiotic delivery system (EcN@Nbs-NP@API-1) that combines Pin1 inhibition with PD-L1 blockade to enhance immunotherapy. This system uses Escherichia coli Nissle 1917 (EcN) to selectively deliver nanoparticles encapsulating the Pin1 inhibitor API-1 to PDAC, enabling sustained release to degrade the fibrotic stroma and upregulate PD-L1 on tumor cells, promoting immune infiltration. Engineered EcN also produces anti-PD-L1 nanobodies in situ, synergizing with API-1 to boost CD8+ T cell-mediated immunity. In orthotopic PDAC mouse models, this strategy remodels the TME, enhances immune cell infiltration, and improves antitumor response while minimizing systemic toxicity. Moreover, it shows efficacy in other ECM-rich tumors, such as triple-negative breast cancer, highlighting its broader potential. This work presents a promising platform to overcome immunotherapy resistance in solid tumors.

Quinoline, isoxazole, and pyridothiazolopyrimidinone derivatives are novel compounds with significant biological activity, exhibiting anticancer properties and holding promising therapeutic applications.

This study aims to develop a receptor-dependent 4D-QSAR model to overcome key limitations of traditional QSAR, including its dependency on molecular alignment and poor performance with small datasets, by integrating ligand - target interaction information.

Melanoma is a type of aggressive cancer distinguished by its high propensity for recurrence, the development of metastases, and an unfavorable outlook for recovery. Treatment modalities for melanoma encompass surgery, immunotherapy, and targeted therapies. In recent decades, berberine has garnered attention for its significant anticancer properties across various cancer types. This review systematically examines the molecular mechanisms of berberine in melanoma, particularly its modulation of critical signaling pathways, including B-RAF/MEK/ERK, PI3K/AKT, and NF-κB, which are essential for regulating melanoma cell proliferation and promoting apoptosis. Furthermore, berberine activates AMP-activated protein kinase, leading to the inhibition of cyclooxygenase-2, thereby reducing melanoma cell migration and invasion through decreased inflammation and enhanced cellular energy regulation. It also induces mitochondrial dysfunction and oxidative stress, promoting apoptosis while simultaneously inhibiting epithelial-to-mesenchymal transition, a key process in metastasis. Additionally, berberine modulates the immune microenvironment through Toll-like receptors, cytokine networks, and the regulation of various immune cells, thereby enhancing its antitumor effects. Recent studies have shown that the therapeutic effect of berberine is enhanced when used in combination with other therapies, especially immune checkpoint inhibitors, to improve antitumor immune responses. These findings highlight the potential of berberine as a multi-targeted agent for the treatment of melanoma, providing an avenue for further clinical exploration and integration into therapeutic strategies.

This study aimed to investigate the anatomical and functional outcomes of branch retinal vein occlusion (BRVO) eyes treated with anti-vascular endothelial growth factor (anti-VEGF) injections using a novel one and stepped pro re nata protocol. This retrospective case series evaluated the electronic medical records from 22 BRVO patients who were treated with anti-VEGF agents under our novel "One and Stepped PRN" protocol at a single tertiary medical center between January 2016 and October 2022. Outcomes of interest included best-corrected visual acuity and central retinal thickness. Twenty-two treatment-naive BRVO eyes (14 males, 8 females) were included. The mean age was 65.82 ± 10.88 years. Average follow-up was 54.45 ± 7.65 weeks. 7 (31.81%) received mainly Ranibizumab, and 15 (68.18%) received mainly Aflibercept. The baseline average best corrected distance visual acuity was 45.86 ± 19.46 Early Treatment of Diabetic Retinopathy Study letters, and the baseline average central retinal thickness was 562.5 ± 164.02 μm. The mean number of injections received was 3.54 ± 1.74. Average best corrected distance visual acuity improvement was 23.91 ± 17.36 Early Treatment of Diabetic Retinopathy Study letters (P < .0001) and average central retinal thickness improvement was 245.55 ± 153.31 μm (P < .0001). Our results were comparable to the BRAVO and VIBRANT trials while comparatively using fewer anti-VEGF injections. In summary, our novel anti-VEGF protocol applied under real-world conditions achieved good anatomical and visual outcomes among treatment-naive BRVO eyes.

The advent of immune checkpoint inhibitors has introduced innovative therapeutic paradigms for the management of human epidermal growth factor receptor 2 (HER2)-negative advanced gastric or gastroesophageal junction cancer (GC/GEJC). However, the efficacy and safety of programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy versus chemotherapy alone in patients with HER2-negative advanced GC/GEJC remain contentious. The comparability among different subgroups is not fully understood, necessitating the identification of optimal patient demographics and the exploration of potential biomarkers.

However, this study has several limitations that must be acknowledged. First, the non-randomized allocation of treatment duration introduces potential selection bias, particularly as frailer patients were more likely to receive shorter therapeutic cycles, which may have confounded outcome assessments. Background: Although the standard 28-day venetoclax (VEN) regimen combined with azacitidine (AZA) improves outcomes in elderly patients with acute myeloid leukemia, emerging evidence suggests that shorter VEN cycles may maintain efficacy with enhanced safety. We retrospectively analyzed 90 treatment-naive elderly patients with acute myeloid leukemia receiving VEN + AZA (VA): 47 patients (14-day VEN) and 43 patients (28-day VEN). The outcomes included clinical remission rates, hematologic recovery, adverse events, and survival metrics. Both groups achieved comparable clinical remission rates (CRc: 57.4% vs 58.1%, P = .947). The 14-day cohort demonstrated significantly faster neutrophil recovery (median 12.5 vs 26 days, P < .01) and reduced febrile neutropenia (73.3% vs 90.9%, P < .05), with trends toward fewer grade ≥3 infections. At a median follow-up of 494 days, no significant differences in median overall survival (OS: 494 vs 578 days, HR = 1.17, 95%CI 0.64-2.14) or event-free survival (416 vs 454 days, HR = 1.09, 95%CI 0.61-1.96) were observed. A 14-day VA regimen showed antileukemic efficacy comparable to the 28-day protocol while mitigating myelosuppressive sequelae. This abbreviated approach may optimize tolerability in frail elderly patients who are ineligible for prolonged low-intensity chemotherapy. Prospective validation is warranted to refine risk-adapted dosing strategies.

Ferroptosis is a nonapoptotic form of cell death characterized by lethal membrane lipid peroxidation. This mechanism was first characterized in cancer cells well over a decade ago, and there is much enthusiasm for the concept that certain cancers may be treated by inducing ferroptosis. However, therapies that engage ferroptosis have yet to enter clinical testing. In this Review, we highlight the gap between our rapidly expanding knowledge of the ferroptosis mechanism and its translation into cancer therapies. We discuss the known challenges that may be slowing ferroptosis therapies from reaching the clinic.

Objective: To explore the application value of machine learning algorithms in constructing a predictive model for cardiovascular toxicity in breast cancer patients receiving anthracycline-based chemotherapy. Methods: This study was a retrospective cohort study. The female patients with breast cancer who received anthracyclines in the Affiliated Cancer Hospital of Xinjiang Medical University from January 2020 to December 2023 were enrolled. The endpoint event was abnormal electrocardiogram (ECG). According to whether the patients had ECG abnormalities during chemotherapy, they were divided into the ECG abnormal group and the ECG normal group. The dataset was divided into the training set and the test set at a ratio of 8∶2, and logistic regression, random forest, extreme gradient boosting (XGBoost), support vector machine (SVM) and multilayer perceptron (MLP) were used to construct a risk prediction model for cardiovascular toxicity in breast cancer patients, and the receiver operating characteristic curve, calibration curve and clinical decision curve were used to evaluate the model. Results: A total of 731 female patients with breast cancer, aged (51.6±9.4) years, were enrolled. The follow-up time was (130.3±37.1) days. There were 333 cases in the ECG abnormal group and 398 cases in the ECG normal group. Seven factors influencing cardiovascular toxicity were identified, including age, menstrual history, diabetes, combination therapy with trastuzumab, combination therapy with dexrazoxane, creatine kinase isoenzymes, and α-hydroxybutyrate dehydrogenase. In the training set, the area under the curve (AUC) for the logistic regression, random forest, XGBoost, SVM, and MLP models was 0.712, 0.863, 0.774, 0.813, and 0.733, respectively. In the test set, the AUC was 0.671, 0.778, 0.746, 0.771, and 0.705, respectively. Calibration curves and clinical decision curves showed that the random forest model performed the best. Conclusion: Models constructed with machine learning algorithms show promise in predicting cardiovascular toxicity in breast cancer patients receiving anthracycline-based chemotherapy, with the random forest prediction model performing the best.