The chemical constituents of the ethyl acetate extract from Achyrocline satureioides were rapidly analyzed using ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS/MS) combined with the Global Natural Products Social Molecular Networking(GNPS) molecular network. The mass spectrometric characteristics of the phloroglucinol compounds were clarified. Guided by these features, systematic isolation was performed using ODS-C_(18), Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC). The structures were elucidated using modern spectroscopic techniques such as nuclear magnetic resonance(NMR) spectroscopy and high-resolution mass spectrometry(HR-MS). A total of 38 compounds were identified from the ethyl acetate fraction by mass spectrometry, including 23 flavonoids. Additionally, 18 compounds were isolated from this fraction. Among them, compound 1 was a new unsaturated fatty acid, and compounds 2, 3, and 7-10 were phloroglucinols. Compounds 2, 3, 7, and 8 were obtained from this plant for the first time. The in vitro anti-proliferative activities of compounds 2, 3, and 7-10 against the non-small cell lung cancer cell lines A549 and H1975 were evaluated using the CCK-8 assay. Compound 8 exhibited significant anti-lung cancer activity. This integrated approach using LC-MS/MS combined with GNPS enables efficient analysis of the chemical components in the ethyl acetate fraction of A. satureioides and facilitates the guided isolation of phloroglucinol compounds, thereby enriching the understanding of its material basis.

The incidence and mortality of malignant tumors remain persistently high, while current clinical chemotherapeutic agents are often limited by significant drug resistance and adverse reactions. Consequently, small-molecule compounds derived from traditional Chinese medicine(TCM) have emerged as a focus in anti-tumor research owing to their advantages of multi-targeting action and low toxicity. As the core active component of Glycyrrhiza uralensis, glycyrrhizic acid(GA) is an oleanane-type pentacyclic triterpenoid saponin, constituting 5%-11% of the total content of G. uralensis. Its anti-tumor activity has been validated across various tumor systems, with mechanisms of action encompassing key processes such as cell cycle arrest, induction of tumor cell apoptosis, inhibition of tumor angiogenesis, blockage of invasion and metastasis, regulation of the tumor immune microenvironment(TIME), and alleviation of chronic inflammation. In terms of its therapeutic value, the combination of glycyrrhizic acid with other agents, such as tanshinone Ⅱ_A(Chinese medicine) or cisplatin(conventional chemotherapy) can achieve enhanced efficacy, reduced toxicity, targeted delivery, and reversal of drug resistance. This positions GA as possessing dual values, functioning both as a therapeutic agent and as a drug delivery carrier. This review systematically summarized the anti-tumor pharmacological activities, mechanisms, combined medication potential, and safety profiles of GA. It elaborated on the network mechanism of core regulatory hubs, analyzed the limitations of current research, and proposed targeted strategies for clinical translation. This work aims to provide a reference for the transition of GA from fundamental research to clinical application, while also offering a paradigm for the development of anti-tumor small-molecule compounds from TCM.

Bufonis Venenum, the dried secretory product from the postauricular and cutaneous glands of Bufonidae, exerts antitumor activity primarily through bufadienolides. This review systematically summarizes the molecular mechanisms of key bufadienolides, including cinobufagin, bufalin, resibufogenin, bufotalin, arenobufagin, gamabufotalin, and cinobufotalin, in the treatment of malignant tumors over the past five years. Current evidence demonstrates that these compounds exert broad-spectrum antitumor effects through multi-target and multi-pathway modulation. In inhibiting tumor cell proliferation, these compounds primarily regulate signaling pathways such as mitogen-activated protein kinase(MAPK), phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT), and signal transducer and activator of transcription 3(STAT3). In inducing cell death, they eliminate malignant cells through multiple modalities including mitochondrion-mediated apoptosis, ferroptosis, and autophagy. In suppressing invasion and metastasis, they modulate epithelial-mesenchymal transition(EMT), matrix metalloproteinase(MMP) expression, and macrophage polarization within the tumor microenvironment. Furthermore, these compounds inhibit angiogenesis, enhance chemosensitivity, activate antitumor immune responses, and regulate epigenetic modifications. Combination therapy studies reveal that bufadienolides exhibit synergistic efficacy when being combined with clinical chemotherapeutic agents, and TCM preparations containing these compounds demonstrate antitumor properties through multi-target regulation. This review elucidates the antitumor molecular mechanisms of bufadienolides, aiming to provide a theoretical basis for further mechanism investigation and clinical translation.

Five undescribed nupharidines, namely amidonupumones A-C (1-3), amidonupumol A (4), and dinupharolutine (7), along with twelve known analogues (5, 6, 8-17) were isolated from Nuphar pumila. Their structures were elucidated by extensive spectroscopic data, ECD, NMR calculations, and X-ray diffraction. Among them, compounds 1-4 represent the first alkaloids containing an amide structure isolated from N. pumila. In vitro bioassays revealed that compounds 7 and 11 exhibited broad-spectrum cytotoxic activity at a concentration of 40 μM.

Melanoma remains one of the most aggressive forms of skin cancer, with limited therapeutic options and significant treatment-related toxicity. In this study, we evaluated the biological activity of a novel dibenzoylmethane derivative, IDPIP, focusing on its cytotoxic, anti-migratory, and pro-apoptotic effects in melanoma cells. IDPIP exhibited pronounced and selective cytotoxicity in murine and human melanoma cell lines, with significantly lower toxicity to non-tumor cells. Notably, IDPIP demonstrated greater potency and selectivity than a clinically used chemotherapeutic agent, with a selectivity index of 23.44, indicating a more favorable therapeutic window. Morphological and flow cytometric analyses revealed that IDPIP induces apoptosis in a dose-dependent manner (up to 90% mortality), involving activation of both intrinsic and extrinsic pathways, as evidenced by caspase-9 and caspase-8 activation assay, respectively. In addition to its cytotoxic effects, IDPIP impaired melanoma cell migration and invasion in vitro, as demonstrated by PMA-induced wound-healing and transwell assays. Treated cells exhibited morphological alterations consistent with reduced adhesion and cytoskeletal disruption. IDPIP treatment was also associated with the accumulation of autophagy-related vesicular structures in this process. Furthermore, using optical tweezers, we demonstrated that IDPIP is capable of interacting with the minor groove of double-stranded DNA. This interaction may contribute to cellular stress responses associated with apoptosis and impaired cell motility. In summary, IDPIP exhibits selective cytotoxicity, promotes apoptosis, and impairs melanoma cell migration in vitro, supporting its potential as a promising candidate for further investigation. Additional studies, including evaluation of DNA damage response pathways and in vivo models, will be necessary to fully elucidate its mechanism of action and therapeutic relevance.

Venetoclax, a selective BCL-2 inhibitor, demonstrates efficacy in acute leukemia (AL) but variable pharmacokinetics. Therapeutic drug monitoring (TDM) may provide valuable pharmacologic insights for optimizing venetoclax therapy. This study explored the factors influencing plasma venetoclax concentrations and their correlation with febrile neutropenia (FN), aiming to establish predictive thresholds.

This study presents a preliminary investigation into the antimicrobial, antibiofilm, and antiproliferative potential of Eremothecium coryli, an endophytic fungus isolated from the seeds of Basella alba L. The biological activities were evaluated using a crude extract-based screening study, employing the lyophilized cell-free supernatant (LCFS) of the fungal culture. Antibacterial and antibiofilm activities were assessed against selected multidrug-resistant bacterial pathogens, while antiproliferative activity was evaluated against breast cancer cell lines and a normal breast epithelial cell line. The LCFS demonstrated measurable antibacterial activity and significant biofilm-inhibition in a concentration-dependent manner. In cytotoxicity assays, selective growth inhibition of breast cancer cell lines was observed when compared with normal cells. Chemical profiling using Liquid Chromatography-Mass Spectrometry and Gas Chromatography-Mass Spectrometry enabled putative metabolite identification, revealing the presence of compounds previously reported to exhibit antimicrobial and anticancer activities. However, these identifications are tentative and based on spectral library matching. Overall, this preliminary investigation highlights the biological potential of E. coryli-derived metabolites. Further purification and validation are necessary to confirm compound identities, elucidate mechanisms of action, and assess in vivo relevance.

Immune checkpoint inhibitors-induced diabetes mellitus (ICI-DM) is a rare but potentially life-threatening endocrine immune-related adverse event, often characterized by abrupt onset of insulin deficiency and frequent presentation with diabetic ketoacidosis and difficulty with daily management with the available therapies. Lung cancer patients represent a substantial proportion of reported cases, reflecting the widespread use of PD-1/PD-L1 inhibitors in thoracic oncology. We report on the case of an elderly patient with metastatic lung adenocarcinoma treated with pembrolizumab who developed severe DM requiring permanent insulin therapy and leading to treatment discontinuation. The patient was subsequently followed over a prolonged period, during which oncological disease remained under sustained control despite immunotherapy interruption. We describe the clinical course, diagnostic workup, and multidisciplinary management, and review current guideline recommendations addressing acute metabolic management, diabetic treatment, and decision-making regarding continuation of immunotherapy. This case highlights the complexity of managing ICI-DM in real-world clinical practice. The current guidelines may help in broad terms. Although guidelines have been published, they remain cursory. Nevertheless, therapeutic decisions should ultimately be individualized through close multidisciplinary collaboration.

Parasite-derived molecules have emerged as a promising source of natural bioactive compounds with immunomodulatory and antitumor properties, attracting increasing attention in cancer research. Derived from both protozoan and helminth parasites, these molecules exhibit diverse biological activities that extend beyond parasite survival and represent a novel resource for cancer therapy. Accumulating evidence demonstrates that parasite-derived molecules suppress tumor progression through complementary immune-mediated and non-immune mechanisms, including activation of innate and adaptive antitumor immunity, remodeling of the tumor microenvironment, induction of apoptosis and autophagy, inhibition of angiogenesis and metastasis, and regulation of tumor metabolism. Recent preclinical studies have demonstrated encouraging therapeutic efficacy across multiple tumor models, including melanoma, lung cancer, colorectal cancer, breast cancer, hepatocellular carcinoma, and other malignancies. In addition to summarizing the major classes of parasite-derived molecules and their mechanisms of action, this review highlights recent advances in translational research, including combination therapeutic strategies, immunogenicity and safety, delivery system optimization, and manufacturing and regulatory considerations. Despite encouraging preclinical findings, substantial challenges remain before clinical translation can be achieved. By integrating current mechanistic evidence with emerging translational perspectives, this review provides a comprehensive overview of parasite-derived molecules as potential anticancer agents and offers insights to facilitate their future development and clinical application in cancer therapy.

Malignancy remains a major cause of late morbidity and mortality in kidney transplant recipients, largely due to chronic immunosuppression and impaired tumor immune surveillance. Mammalian target of rapamycin inhibitors have antiproliferative and antiangiogenic properties and are frequently used in recipients considered to be at increased oncologic risk. However, their protective effect against de novo malignancy is not absolute. Here, we report 2 cases of severe malignancies that developed in kidney transplant recipients after conversion from calcineurin inhibitors to sirolimus following polyomavirus-associated nephropathy. The first patient, a 55-year-old man, developed prostate adenocarcinoma 6 years after transplant and 4 years after conversion to sirolimus. The diagnosis was established during evaluation for severe anemia and graft dysfunction. The second patient, a 35-year-old woman, developed primary central nervous system posttransplant lymphoproliferative disorder 4 years after transplant and 2 years after conversion to sirolimus. Histopathologic examination confirmed an aggressive lymphoma without detectable Epstein-Barr virus infection. These cases illustrate that mammalian target of rapamycin inhibitor-based immunosuppression does not eliminate the risk of solid or hematologic malignancy. Cumulative immunosuppressive exposure, viral complications, and delayed conversion may contribute to persistent oncogenic risk. Careful long-term oncologic surveillance and individualized immunosuppressive management remain essential in kidney transplant recipients.

Clinical treatment of prostate cancer, particularly metastatic castration-resistant prostate cancer (mCRPC), mainly depends on targeting prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II (GCPII). Toward this, small molecule-drug conjugates (SMDCs), consisting of a PSMA-targeting ligand along with a chemotherapeutic, have emerged as an important targeted therapeutic tool. Herein, we have designed 39 ligands with varied targeting heads and linkers and have analyzed their efficacy in silico using molecular docking and molecular dynamics simulation. The best-docked compound was further synthesized, conjugated with doxorubicin via an acid-labile imine linkage to yield a novel PSMA-Dox conjugate. This conjugate was evaluated in vitro in PSMA-positive (LNCaP and C4-2 cells) and PSMA-negative (PC3 cells) to establish its selectivity toward PSMA, as well as to ascertain its selective cytotoxicity toward PSMA-positive cells. Further, cell cycle analysis confirmed the efficacy of the conjugate to induce apoptosis in PSMA-positive cancer cells. Thus, this study demonstrates a new SMDC which can serve as a template for creating new analogs with enhanced targeting and anticancer efficacy.

Triple-negative breast cancer (TNBC) displays pronounced molecular heterogeneity and metastatic propensity, which correlates with its poor clinical prognosis. Crucially, radiotherapy (RT) resistance serves as a pivotal contributor to treatment failure and disease advancement in TNBC. To address this challenge, we developed BWFP, which is achieved by loading WZB117 and FIN56 onto bismuth-based metal organic framework with radiosensitization effect and surface modifying pH-responsive DSPE-PEOz. Under the acidic tumor microenvironment, BWFP controllably releases its payload: WZB117 suppresses glucose uptake through GLUT1 downregulation, thereby limiting NADPH production and inducing cystine accumulation alongside cysteine depletion, which concurrently triggers disulfidptosis and relieves ferroptosis resistance. Meanwhile, the released ferroptosis inducer FIN56 further amplifies ferroptosis by degrading GPX4. In addition to this, BWFP enhances RT efficacy through radiosensitization effects, consequently intensifying DNA damage. In a word, BWFP demonstrates robust anti-tumor activity in TNBC models by concomitantly inducing disulfidptosis and ferroptosis with synergized radiosensitization.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with lung adenocarcinoma (LUAD) being its most prevalent histological subtype, which is plagued by severe drug resistance and dismal long-term survival. Current treatment approaches are often limited by drug resistance and metastasis. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, represents a promising novel therapeutic target to address these unmet clinical needs.

In recent years, immune-based therapies, particularly checkpoint inhibitors, have been developed to interfere with tumor immune escape. Among various molecular targets, the PD-1/PD-L1 axis represents a central mechanism of tumor-driven immune evasion and a major target for restoring T-cell-mediated anti-tumor activity. Several blocking monoclonal antibodies have been developed to restore antitumor immunity, and anti-PD-1/PD-L1 antibodies have transformed the treatment of solid tumors, including colorectal cancer (CRC). In the colon, the PD-1/PD-L1 axis plays a dual and context-dependent role. During the early stages of intestinal inflammation, such as in inflammatory bowel disease (IBD), PD-1/PD-L1 signaling contributes to immune tolerance and mucosal protection. However, persistent activation of this pathway may become detrimental during the colitis-to-cancer transition, promoting immune evasion and tumor progression. Immune checkpoint inhibitors, such as nivolumab and pembrolizumab, currently approved for specific subsets of CRC, exert their effects by blocking the interaction between PD-1 and PD-L1, thereby restoring antitumor immune responses. Their use, either as monotherapy or in combination regimens, has demonstrated promising efficacy in advanced and mismatch repair-deficient CRC. This review summarizes the biphasic role of PD-1/PD-L1 in IBD and CRC, with particular emphasis on the therapeutic application of PD-1/PD-L1 blockade in CRC. It highlights monoclonal antibody-based approaches and emerging combination strategies, and finally examines current clinical trial evidence, highlighting ongoing challenges, including primary and acquired resistance to anti-PD-1/PD-L1 therapies.

Actinomycins constitute a class of bioactive compounds known for their potent cytotoxic properties. Among them, actinomycin D, isolated in the 1940s from Streptomyces antibioticus, is the most extensively studied derivative. Structurally, actinomycins are characterized by a planar phenoxazinone chromophore flanked by two cyclic pentapeptides. They exert their biological effects primarily through DNA intercalation and transcription inhibition. Despite its remarkable bioactivity, the clinical application of actinomycin D is limited by significant adverse effects, including hepatotoxicity and restricted selectivity. These limitations underscore the need for structurally optimized analogs with improved therapeutic profiles and reduced toxicity. Over the decades, natural product discovery, precursor-directed biosynthesis, and synthetic modification have yielded more than 70 structurally distinct derivatives, incorporating variations in both the peptide rings and the chromophore core. These structural modifications have resulted in diverse antibacterial, antiviral, and cytotoxic activities. Thus, this review critically examines the historical development, chemical diversity, and in vitro and preclinical bioactivity of actinomycin derivatives, highlighting key structural modifications over time and discussing their implications for future drug development.

Photodynamic therapy (PDT) is a clinically approved therapeutic modality with great potential for the treatment of cancers due to its excellent spatiotemporal selectivity and noninvasivenes. A combination of light-controlled chemotherapy (PACT) and PDT in one molecule has the potential to overcome crucial drawbacks of both Pt-based chemotherapy and PDT via a synergetic effect. Herein, we report a Pt(IV)-BODIPY agent for dual light-controlled chemophotodynamic therapy, a Pt(IV) prodrug with a BODIPY orthogonal dimer in the axial position. The orthogonal arrangement of the fluorophores results in a long-lived, "heavy-atom-free" triplet state of the dimeric fluorophore. The high quantum yield of singlet oxygen for the dimer fluorophore and the Pt(IV) prodrug based on it was confirmed, and the formation of the triplet state was demonstrated by flash photolysis. The excellent photosensitive properties of the Pt(IV) prodrug on SK-BR-3 and MCF-7 tumor cells demonstrate photocontrolled toxicity and potential for the development of dual therapy conjugates.

Cervical cancer is the fourth most common cancer and the fourth leading cause of cancer‑related mortality among women worldwide. Tangeretin (TAN), a polymethoxylated flavonoid derived from citrus fruit peel, exhibits relatively high structural stability due to its methoxy groups and exerts anticancer effects in various malignancies, including lung, liver and breast cancer. However, to the best of our knowledge, the anticancer effects of TAN in cervical cancer remain insufficiently explored. The present study investigated the mechanisms underlying the anticancer effects of TAN on the CaSki cervical cancer cell line. Cell viability was evaluated using the EZ‑Cytox cell viability assay. The colony formation and cell cycle arrest assays demonstrated that TAN inhibited cell proliferation by inducing G1 phase arrest. The wound‑healing and Transwell migration assays demonstrated that TAN could reduce the migratory ability of CaSki cells, and the Annexin V/propidium iodide staining assay revealed that TAN increased the apoptotic cell population. Mitochondrial reactive oxygen species (ROS) were identified using MitoSOX™ staining and the mitochondrial membrane potential (MMP) was detected using JC‑1 staining. The findings of these assays suggested that TAN could increase mitochondrial ROS levels and decrease mitochondrial MMP in CaSki cells. Western blot analysis showed that TAN upregulated the protein expression levels of E‑cadherin and Bax. In addition, TAN restored the tumor suppressor protein p53. Collectively, these findings suggested that may exhibit anticancer activity in CaSki cells.

Advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinomas are characterized by an aggressive course and a very poor prognosis. Due to the limited benefit of immunotherapy in patients with HER2-negative tumors, new therapeutic targets are sought. Zolbetuximab is a chimeric monoclonal antibody targeting the CLDN18.2 protein, which is overexpressed in 50-80% of gastric cancers.

Rituximab and obinutuzumab share the CD20 target but are used across distinct B-cell non-Hodgkin lymphoma (B-NHL) subtypes, treatment backbones, and clinical eras. Their real-world adverse event (AE) reporting patterns remain incompletely characterized.

Adipose-derived stem cells (ADSCs) are widely used in regenerative medicine, but their functionality declines under chemotherapeutic stress. Doxorubicin (Dox) is an effective anticancer agent known to induce long-term toxicity in healthy tissues. Increasing evidence suggests that Dox promotes cellular dysfunction, including apoptosis, promotion of oxidative stress, and premature senescence. The SAPK/JNK signaling pathway is implicated in stress responses and may contribute to Dox-induced aging in stem cells. However, its role in ADSC senescence and functional decline remains unclear. This study evaluated the effects of Dox on ADSC viability and aging-associated processes, with a focus on SAPK/JNK signaling. ADSCs exposed to 0.1-100 μM Dox for 24 h showed reduced mitochondrial activity and ATP levels at clinically relevant doses (5 μM), along with disrupted cell cycle progression and cytoskeletal alterations. Dox induced both apoptosis and premature senescence and increased oxidative stress. These effects were accompanied by alterations in SAPK/JNK pathway expression. Overall, Dox promoted ADSC dysfunction, highlighting potential limitations in the therapeutic use of ADSCs during chemotherapy and emphasizing the need for protective strategies. Alterations in the SAPK/JNK signaling pathway were observed in response to Dox-induced stress, suggesting that this pathway may contribute to the cellular stress response. These findings suggest that the development of approaches to preserve ADSC function and mitigate Dox toxicity is critical for improving the safety and efficacy of regenerative medicine applications.