Pancreatic cancer remains one of the most aggressive malignancies with limited therapeutic options and poor prognosis. Erlotinib (OSI-774), a small-molecule tyrosine kinase inhibitor (TKI), is clinically used in combination with gemcitabine, yet its efficacy is limited by modest improvements in overall survival (OS) and significant side effects. The aggregation of erlotinib in aqueous solutions further restricts its bioavailability. This study investigates the potential of Congo red (CR), a supramolecular carrier, to enhance the therapeutic impact of erlotinib against pancreatic cancer cells. Biophysical analyses using UV-visible spectroscopy (UV-Vis) and dynamic light scattering (DLS) confirmed the formation of stable CR-erlotinib co-aggregates with optimal molar ratio of 5:1. The effects of erlotinib alone and in combination with CR (CR:OSI-774) were evaluated on two pancreatic cancer cell lines (PANC-1 and BxPC-3). CR:OSI-774 complexes demonstrated significantly lower IC50 and IC90 values compared to erlotinib monotherapy, indicating enhanced anti-proliferative effects. While erlotinib induced apoptosis, CR:OSI-774 primarily triggered necrotic cell death. Importantly, both compounds significantly inhibited cancer cell migration and invasion, with CR:OSI-774 showing superior inhibition of invasive capacity. CR alone did not negatively affect cell viability or apoptosis/necrosis rates. Nanomechanical measurements using atomic force microscopy revealed an increase in cellular stiffness after treatment, particularly in cells exposed to the CR-erlotinib complex, suggesting changes in cytoskeletal organization associated with reduced motility. Furthermore, quantitative protein analysis using the Jess capillary electrophoresis system revealed a decrease in AKT phosphorylation without significant changes in total AKT levels, indicating effective modulation of EGFR signaling via supramolecular aggregation. These findings suggest that supramolecular aggregation with CR represents a promising strategy to enhance erlotinib efficacy in pancreatic cancer therapy while potentially reducing systemic toxicity. The approach opens new avenues for personalized medicine and targeted anti-cancer therapy.

Doxorubicin (DOX) is a commonly prescribed chemotherapeutic agent whose clinical application is limited by its toxicity to rapidly dividing organs, particularly the testes.This study explored the protective potential of ferulic acid-loaded niosomes (FA-NIO) against DOX-induced testicular dysfunction in rats and elucidated the underlying molecular mechanisms. Forty male rats were allocated into four groups: Group 1 was given saline, Group 2 was given DOX, Group 3 was given DOX + free FA, and Group 4 was given DOX + FA-NIO. Serum reproductive hormone levels, testicular oxidative stress indices, and the expression of genes and proteins relevant to NLRP3 inflammasome signaling, apoptosis (Bax and Bcl-2), and steroidogenesis (StAR, CYP11A1, and 3β-HSD) were assessed, along with histopathological changes in the testicular tissue. DOX administration significantly increased MDA (malondialdehyde) while suppressing antioxidant defences, accompanied by hormonal imbalance, severe histopathological damage, upregulation of Bax, NLRP3, and IL-1β, downregulation of Bcl-2, and inhibition of steroidogenic gene expression. On the other hand, these changes were partially mitigated in the DOX + free FA group. Notably, FA-NIO treatment reduced histopathological damage, normalised reproductive hormone levels, markedly increased steroidogenesis-related gene expression, suppressed apoptotic and inflammasome-related gene expression, and greatly restored antioxidant capacity. Compared with DOX + free FA, FA-NIO consistently demonstrated greater protective efficacy. In summary, FA-NIO targets oxidative stress-mediated apoptosis, attenuates NLRP3 inflammasome-related signaling, and restores steroidogenic function, thereby successfully attenuating DOX-induced testicular toxicity. These results suggest that FA-NIO may represent a promising nanotherapeutic strategy for attenuating chemotherapy-induced reproductive toxicity in a rat model.

The innovation of a therapeutic agent with dual anti-inflammatory, anticancer and reversing the dynamic of microtubules like colchicine was crucial. VEGFR2 inhibition has been established as a therapeutic approach for managing cancer, the colchicine site, situated on ß-tubulin and α-tubulin was also considered in cancer development, and metastasis. Moreover, uncontrolled inflammation predisposes to pleiotropic effects leading to cancer development and promoting all stages of tumorigenesis. A polymeric state of a novel one-dimensional palladium-based metal-organic framework (1D Pd-MOF), resulting from the coordination of pyrazine with palladium nuclei to achieve the more pronounced effect of polynuclear characteristics of palladium compared to mononuclear compounds, was designed, synthesized, and screened for its anticancer activity against the A549 lung cancer cell line, with comparison to normal cells. The characterization was performed using different techniques and supported by DFT investigations. The 1D Pd MOF exhibited a potent cytotoxic effect, with an IC50 value of 78.21 ± 0.41 µg/mL against the A549 lung cancer cell line, while showing minimal toxicity toward the normal WI-38 cell line. To investigate the inhibitory activity of the 1D Pd-MOF towards VEGFR2 kinase and to confirm itseffective molecular target, VEGFR2 kinase inhibition was evaluated. The results demonstrated promising VEGFR2 inhibitory activity with a moderate IC50 value of 0.658 ± 0.023 µg/mL, compared with an IC50 value of 0.079 ± 0.003 µg/mL for sorafenib, the reference drug. This activity was further supported by significant inhibition of VEGFR2 gene expression and protein levels compared with untreated control cells. Our results revealed that 1D Pd-MOF is a promising tubulin-interacting compound, as it binds to the colchicine-binding site on tubulin and competes with colchicine in vitro, with an IC50 value of 3.350 ± 0.21 µg/mL. These findings confirm tubulin as a molecular target of the 1D Pd-MOF and support its observed cytotoxic activity. Furthermore, the 1D Pd-MOF significantly upregulated the expression levels of BAX, P53, and caspase-3 genes, while downregulating CDK4, cyclin D1, and BCL2 genes relative to the control group, suggesting growth inhibition and induction of apoptosis in treated lung carcinoma cells. These findings confirm that the 1D Pd-MOF exerts a clear anticancer effect by triggering programmed cell death through apoptosis. In addition, treatment with the 1D Pd-MOF resulted in substantial accumulation of cells in the sub-G1 fraction, accompanied by a corresponding reduction in the G2/M phase, indicating that its cytotoxic efficacy is primarily mediated through apoptosis induction rather than cell cycle arrest at a specific checkpoint. The anti-inflammatory activity of the 1D Pd-MOF was established by its inhibition of nitric oxide (NO) production in LPS-stimulated RAW cells. Molecular docking studies showed good agreement with the experimental biological findings.

Nanotechnology provides innovative solutions to biomedical and agricultural challenges, and silver nanoparticles (AgNPs) are of particular interest due to their broad-spectrum bioactivity. This study aimed to green-synthesize AgNPs using Buddleja asiatica leaf extract, characterize the nanoparticles, and evaluate antibacterial, antioxidant, anticancer, and phytotoxic/phytostimulatory activities. AgNP formation was confirmed by UV-visible spectroscopy (SPR peak at 420 nm). XRD verified a crystalline face-centered cubic structure, while SEM showed predominantly near-spherical nanoparticles (10-22 nm). FTIR indicated plant-derived functional groups involved in stabilization. Biologically, BA-AgNPs exhibited strong antibacterial activity against a Gram-positive clinical isolate (Streptococcus sp.) and Gram-negative bacteria, with the largest inhibition zone of 14 ± 0.57 mm at 0.9 mg/mL. Antioxidant activity reached 88.12% DPPH scavenging at 100 ppm, compared with 80.90% for ascorbic acid under the same assay conditions. BA-AgNPs showed concentration-dependent cytotoxicity in RD cells, with cell death ranging from 87.00% at 100 mg/mL to 5.33% at 0.39062 mg/mL; however, IC50 is reported only as an estimated range of 6.25-12.5 mg/mL based on the concentration interval where cytotoxicity crossed 50%. In wheat, lower concentrations showed phytostimulatory trends, with the strongest response at 50 mg/L, while 1000 mg/L caused inhibitory effects. This is the first comprehensive report on B. asiatica-mediated AgNP synthesis and multifunctional bioactivity, highlighting BA-AgNPs as a sustainable nanomaterial for antimicrobial, antioxidant, anticancer, and agricultural applications, while emphasizing the need for future stability, mechanistic, and translational safety studies.

Currently, PARP inhibitors (PARPis) have been primarily utilized to treat ‌breast cancer susceptibility gene (BRCA)-mutated triple-negative breast cancer (TNBC), but their application scope is quite narrow. Recently, it has been discovered that suppression of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway sensitizes BRCA-proficient TNBC to PARPis. In the study, a new PARP inhibitor DA1, modulating PI3K/AKT/mTOR pathway, was designed and synthesized. DA1 showed good antiproliferative effects on BRCA-proficient TNBC cells MDA-MB-231, BT549 and MDA-MB-468, with IC50 values of 0.77 ± 0.03, 1.33 ± 0.01 and 0.28 ± 0.02 μM, respectively. Moreover, DA1 potently inhibited PARP-1 and PARP-2, with IC50 values of 2.5 ± 0.8 and 1.4 ± 0.5 nM respectively. Mechanistically, DA1 suppressed the PI3K/AKT/mTOR signaling pathway, increased DNA damage, caused cell cycle arrest in G2/M phase, and accelerated MDA-MB-231 apoptosis. Additionally, DA1 efficiently suppressed MDA-MB-231 cell migration and invasion. It also exhibited remarkable anti-tumor activity in an MDA-MB-231 cell-derived xenograft model at a dose of 20 mg/kg, with significantly superior therapeutic effects compared to Olaparib, Tan IIA or the combo. Overall, DA1 presents a promising lead compound used to treat BRCA-proficient TNBC.

To study the morphological patterns of immune-related cutaneous lesions (irCLs) that occur during antitumor immunotherapy in cancer patients.

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, driven by late-stage diagnosis, metastatic progression, and therapeutic resistance. Src homology region 2 domain-containing phosphatase 2 (SHP2) has emerged as a critical regulator of oncogenic signaling in gastric tumorigenesis, yet its therapeutic targeting remains underexplored. In this study, we evaluated the anti-cancer efficacy of NSC 57774, a novel SHP2 inhibitor, using integrated bioinformatics and functional assays in AGS gastric cancer cells. Analysis of The Cancer Genome Atlas (TCGA) and UALCAN datasets revealed marked upregulation of SHP2 and multiple receptor tyrosine kinases in gastric cancer tissues. NSC 57774 potently inhibited cell proliferation and migration, demonstrating selective cytotoxicity towards cancer cells over non-cancerous fibroblasts. Mechanistically, NSC 57774 disrupted key oncogenic pathways including MAPK/ERK, AKT and STAT3 in a concentration- and time-dependent manner, with higher doses achieving more sustained pathway suppression. NSC 57774 suppressed NF-κB inflammatory signaling at early timepoints and induced cleaved caspase-3 across all treatment groups at 72 hours, indicative of pro-apoptotic activity. A paradoxical late-phase increase in phospho-p38 was observed at 72 hours, consistent with a compensatory pro-apoptotic stress response. Comparative analysis revealed that NSC 57774 outperformed the commercial SHP2 inhibitor NSC 87877 and doxorubicin in reducing viability and migration of gastric cancer cells. Collectively, these findings position NSC 57774 as a promising candidate for targeted gastric cancer therapy, capable of disrupting multiple signaling pathways involved in tumor progression, metastasis, and inflammation, warranting further preclinical and clinical investigation.

Mirvetuximab soravtansine is an antibody-drug conjugate targeting folate receptor alpha (FRα), which is used in the treatment of platinum-resistant ovarian cancer. Its administration is associated with a distinct spectrum of ocular adverse events, representing a clinically relevant limitation of therapy. The most common manifestations include keratopathy, blurred vision, and dry eye symptoms. These effects are generally reversible and manageable upon appropriate ophthalmologic monitoring. This review summarizes the current knowledge regarding the mechanisms, clinical presentation, incidence, prevention, and management of mirvetuximab-associated ocular toxicity.

Monensin, a polyether ionophore widely used in veterinary medicine, has recently emerged as a multimodal anticancer candidate. This review provides a comprehensive overview of preclinical studies showing that monensin exerts selective cytotoxic and anti-progression effects across a wide range of malignancies. Its activity spans breast cancer to leukemia, reflecting both versatility and significant therapeutic potential. In breast cancer, monensin reduces proliferation, induces apoptosis, and enhances chemosensitivity, suggesting a role in combination therapies. In prostate cancer, it disrupts androgen receptor signaling, induces oxidative stress, and triggers mitochondria-dependent apoptosis. In pancreatic cancer, it suppresses EGFR signaling and promotes programmed cell death, while in ovarian and cervical cancers, it inhibits proliferation, migration, and invasion by modulating EGFR and MEK/ERK pathways and enhancing SUMOylation. In renal carcinoma, monensin induces cell-cycle arrest, autophagy, and apoptosis, whereas in bladder and squamous cell carcinoma, it interferes with EGFR-related signaling and lectin-mediated interactions. It selectively kills liver cancer cells through intracellular Na⁺ overload and mitochondrial damage, and in thyroid cancer, it disrupts cellular respiration and AMPK/mTOR signaling. In glioblastoma, it exhibits both anti-tumor and anti-angiogenic effects, while in hematologic malignancies such as leukemia and lymphoma, it induces apoptosis, cell-cycle arrest, and glycosylation alterations. Collectively, these findings highlight monensin as a highly promising, broad-spectrum anticancer candidate. Its multifaceted mechanisms of action and consistent efficacy across diverse tumor types provide a compelling rationale for continued preclinical evaluation and potential clinical translation. These insights position monensin as an innovative therapeutic avenue, offering new hope for the development of versatile and effective cancer treatments.

Conventional photosensitizers (PSs) are hindered by aggregation-caused quenching, limited tissue-penetration depth and off-target toxicity, which restricts their clinical translation for photodynamic therapy (PDT). To tackle these bottlenecks, we constructed an all-in-one nanotheranostic system named F127@546, where a donor-acceptor-type fluorophore (IR-546) with twisted intramolecular charge-transfer (TICT) characteristics is encapsulated within the amphiphilic polymer Pluronic F127. This rational design not only substantially improves biocompatibility but also induces a prominent emission red shift from 605 nm to 900 nm, with an emission tail extending above 1000 nm to realize high-resolution deep-tissue NIR-II imaging. Beyond its NIR-II imaging capability, F127@546 acts as an effective dual-mode photosensitizer upon 660 nm laser irradiation to concurrently produce type-I and type-II reactive oxygen species (ROS). The generated ROS dissipates mitochondrial membrane potential and further initiates melanoma cell apoptosis. In vivo experiments were performed via intratumoral injection of F127@546. We verified that its photodynamic therapy exerted a remarkable inhibitory effect on tumors, accompanied by negligible systemic toxicity. This study provides a generalizable blueprint for fabricating multifunctional nanoplatforms that combine deep tissue imaging and synergistic photodynamic therapy, advancing the development of precision-oriented anti-tumor treatment.

Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown limited efficacy in gastric cancer, primarily due to the rarity of inherent homologous recombination (HR) deficiency. The nuclear Arp2/3 complex was recently implicated in DNA double-strand break repair via HR. Here, we investigate whether pharmacological inhibition of Arp2/3 can induce a functional HR-deficient state to synergize with PARPi in gastric cancer cells.

Glioblastoma (GBM) frequently develops resistance to temozolomide (TMZ), limiting the effectiveness of standard therapy. Histone deacetylase (HDAC) inhibitors have emerged as potential chemosensitizers; however, the comparative performance of these inhibitors and the associated mechanistic impact remain incompletely characterized.

Cancer neuroscience has emerged as a field that explores the bidirectional interactions between tumors and the nervous system. From this perspective, we review the pharmacological and neurobiological effects of kinase inhibitors, which are widely used as anticancer therapeutics. Certain kinase inhibitors not only exert potent antitumor activity but also modulate neural function as a consequence of kinase inhibition. Representative examples include small molecules and therapeutic antibodies targeting the tropomyosin receptor kinase (Trk), rearranged during transfection (RET), vascular endothelial growth factor/ vascular endothelial growth factor receptor (VEGF/VEGFR), epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK) signaling pathways. These agents influence the nervous system through molecular mechanisms, examples of which include TrkA-mediated pain perception and growth differentiation factor 15/RET signaling-dependent appetite regulation. Elucidating these mechanistic intersections between oncogenic and neural signaling can broaden our understanding of tumor-nerve crosstalk.

A common cause of multidrug-resistant (MDR) cancer is imbalanced redox signaling, which reduces the effectiveness of chemotherapy and promotes regrowth of cancer cells. Amplification of thioredoxin reductase (TrxR) and activation of the Keap1-Nrf2-FOXO3 pathway may contribute to enhanced drug efflux, strengthens antioxidant defenses, and resistance to oxidative stress-induced apoptosis in certain tumors. Redox-based drug repurposing offers a promising strategy to overcome MDR by targeting these shortcomings. Repurposing drugs including metformin, auranofin, brusatol, and natural polyphenols increase reactive oxygen species (ROS) and make MDR cells more sensitive to chemotherapy via modulation and inhibiting Nrf2 or TrxR. Nanotechnology advancements and combination of repurposed drugs with anticancer drugs, ferroptosis inducers may improve tumor selectivity while lowering systemic toxicity. Preclinical experiments show effectiveness by suppressing antioxidant pathways, inhibiting efflux pump function, and delivering drugs in a redox-responsive manner. Next-generation tumor-selective delivery systems, adaptive clinical trial designs, and biomarker-driven patient classification based on TrxR expression or Keap1/Nrf2 mutations are the main areas of focus. Translation into clinical practice could be accelerated by combining specific redox profiling, nanocarrier technologies, and pharmacokinetics. For MDR cancer, redox-targeted drug repurposing is an effective, precision-based strategy for recovering chemosensitivity and enhancing treatment outcomes.

Acute myeloid leukemia (AML) remains a highly aggressive hematological malignancy with frequent relapse and limited therapeutic durability. Although venetoclax has provided an important therapeutic option for AML, suboptimal response and treatment resistance continue to restrict its clinical benefit. Here, we developed a venetoclax-loaded lipid nanomedicine, Vene-lipo, to enhance anti-leukemic efficacy. Vene-lipo displayed uniform nanoscale morphology, favorable colloidal stability, and good preliminary biosafety. Compared with free venetoclax, Vene-lipo more effectively suppressed AML cell growth and promoted ROS-associated DNA damage and apoptosis. In vivo, Vene-lipo reduced leukemic burden, alleviated leukemia-associated organ involvement, improved hematological abnormalities, and prolonged survival. These findings demonstrate that lipid nanomedicine-based delivery can potentiate the therapeutic activity of venetoclax and provide a promising strategy for AML treatment.

To assess the protective effects of live combined bifidobacterium, lactobacillus, enterococcus, and glutamine on diarrhea associated with chemotherapy and inflammatory markers in colorectal cancer patients (CCP). A retrospective analysis was conducted on the clinical data of patients with colorectal cancer who received chemotherapy at the People's Hospital of Pailin County, Chongqing from December 2022 to December 2024. There were 59 cases in the control group and 59 cases in the study group. The control group received treatment with triple live bifidobacterium, while the study group received combined treatment with glutamine in addition to the treatment of the control group. We compared levels of inflammatory markers, intestinal barrier functions, immune responses, and diarrhea incidence during chemotherapy. No significant pre-chemotherapy differences were noted in inflammatory or intestinal barrier markers (P > 0.05). Throughout the course of treatment, we observed a reduction in inflammatory markers in both groups (P < 0.05), with the experimental group showing more significant declines. Intestinal barrier functions degraded over time in both groups, with more significant reductions in the study group (P < 0.05). The therapy combining significantly mitigates inflammation, bolsters intestinal and immune functions, and alleviates diarrhea in CCP. Clinical Registration: The authors have nothing to report.

A subset of cancer patients receiving monoclonal antibody PD-1/PD-L1 inhibitors may develop immune checkpoint inhibitor (ICI)-related neurological complications, such as ICI-related myasthenia gravis(MG)-myositis overlap syndrome and ICI-related myocarditis. Standard management typically involves intravenous immunoglobulin (IVIG), plasma exchange (PE), and high-dose corticosteroids. The use of efgartigimod, a neonatal Fc receptor blocker, for the treatment of ICI-related MG-myositis overlap syndrome remains investigational, with only four relevant cases all representing overlap syndromes (MG with myositis, with or without myocarditis) - reported to date.

Immune checkpoint inhibitors (ICIs) can induce a broad spectrum of immune-related adverse events (irAEs), including rare fibroinflammatory autoimmune manifestations. IgG4-related disease (IgG4-RD) has only exceptionally been described following dual ICI therapy.

Immune checkpoint inhibitors (ICIs) activate antitumor immunity by targeting immune checkpoint molecules such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death receptor 1 (PD-1), and programmed death-ligand 1 (PD-L1). They have emerged as a key therapeutic modality for multiple malignancies. Nevertheless, excessive immune activation may trigger a spectrum of immune-related adverse events (irAEs). Though uncommon, uveitis is a sight-threatening irAEs that can result in permanent visual loss. The risk and prognostic outcomes of ICIs-associated uveitis remain poorly defined to date. Therefore, we performed this meta-analysis to systematically assess the correlation of ICIs therapy with uveitis risk and prognosis, with the goal of providing evidence-based recommendations for clinical identification and management of this ocular complication.

4-[4-(Bis(2-(nitrooxy)ethyl)amino)phenyl]butanoic acid (NPB), a phenylbutyrate-derived nitric oxide (NO) donor, has been developed as a potential anticancer agent for pancreatic cancer. In the present study, we investigated the cytotoxic effects of NPB under cellular stress conditions and examined its effects on autophagy-related pathways and hypoxia-inducible factor-1α (HIF-1α) signaling. NPB-induced cell death was enhanced under nutrient-deprived conditions in PANC-1 cells. In addition, NPB induced greater cell death under hypoxic conditions than under normoxic conditions in PANC-1 cells, whereas in BxPC-3 cells, NPB-induced cell death was slightly but significantly lower under hypoxic conditions than under normoxic conditions. Using GFP-LC3-RFP-LC3ΔG reporter cells, NPB suppressed starvation-induced autophagic flux. In pancreatic cancer cells, NPB decreased DAPGreen fluorescence, an indicator of autophagy-related vesicular activity, and increased propidium iodide-positive cells under hypoxic conditions. Western blot analysis showed that NPB induced the accumulation of p62 and LC3 under both normoxic and hypoxic conditions. Under hypoxic conditions, NPB also reduced HIF-1α expression. Under cobalt chloride (CoCl2)-induced HIF-1α-accumulating conditions, NPB and the NO donor NONOate suppressed HIF-1α expression, whereas OH-PB, a non-NO-releasing analog, showed little effect. Furthermore, the proteasome inhibitor MG132 restored HIF-1α accumulation in NPB-treated cells. Time-course analysis under CoCl2-treated conditions showed that NPB reduced HIF-1α expression concomitantly with p62 accumulation. These findings suggest that NPB induces pancreatic cancer cell death, particularly under nutrient-deprived and hypoxic conditions, accompanied by impairment of autophagy-related pathways and NO-dependent, proteasome-associated reduction of HIF-1α.