Angiosarcoma is a rare and aggressive malignancy with limited treatment options. This phase II, multicenter, open-label, single-arm study (AngioCheck) evaluated the efficacy and safety of nivolumab in patients with cutaneous angiosarcoma previously treated with taxane-based chemotherapy.

Drug efflux mediated by transporter proteins is one of the major mechanisms conferring multidrug resistance (MDR) to antimicrobial agents in bacteria and to chemotherapeutics in cancer cells. Therefore, the development or identification of efflux modulators represents a promising strategy to overcome the resistant phenotype. Various chemical compounds have been tested in experimental studies as reversal agents either in combination with antimicrobial or anticancer drugs and have shown sensitizing activity in resistant bacteria or cancer cell lines. Owing to the common resistance mechanisms exhibited by bacteria and cancer cells, the identification of chemical agents with dual reversal activity offers a strategy to simultaneously combat antibacterial and cancer multidrug resistance.

The dense extracellular matrix (ECM) of stroma-rich solid tumors acts as a significant barrier to effective chemotherapy by hindering drug penetration. In this study, a supramolecular hydrogel was successfully developed, enabling the codelivery and sequential release of hydrophilic and lipophilic drugs designed to target the ECM. The hydrogel is easy to prepare, has self-healing properties and excellent biocompatibility. Upon administration, the hydrogel first releases pirfenidone to inhibit collagen production, weakening the ECM, followed by the release of paclitaxel, which improves tumor penetration. The effectiveness of this sequential drug delivery system was validated in both oral squamous cell carcinoma and pancreatic cancer models, a classic example of a tumor with abundant ECM. In vitro experiments showed controlled sequential release profiles, whereas in vivo experiments using cell-derived and patient-derived xenograft models revealed that the hydrogel was more effective at tumor suppression compared to traditional methods. Single administration of the hydrogel led to long-term localized drug release, maintaining higher concentrations of chemotherapeutic agents in the tumor tissue and effectively reducing the tumor volume. This study provided a promising strategy to enhance chemotherapy in ECM-dense tumors, offering an efficient and minimally invasive method for localized, sustained-release cancer therapy.

This study reports the multifunctional potential of gold nanoparticles (AuNPs) biosynthesized by using Salvia splendens leaf extract (SSLE). The biosynthesized AuNPs were characterized by UV-Visible spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering, followed by the assessment of their anti-cancer, anti-oxidant, anti-inflammatory and anti-bacterial potentials. The biosynthesized SSLE-AuNPs showed a characteristic absorbance peak at 559 nm that corresponds to the surface plasmon resonance (SPR) band of the AuNPs. The zeta potential of SSLE-AuNPs was estimated to be ‒ 21 ± 1.9 mV, and TEM analysis confirmed the particles to be spherical with an average size of 94.8 ± 5.1 nm. The SSLE-AuNPs exhibited dose-dependent antioxidant activity, with IC50 values of 218.5 ± 4.2 µg/mL (DPPH) and 185.3 ± 3.7 µg/mL (ABTS), compared to ascorbic acid (32.1 ± 1.8 µg/mL and 28.6 ± 1.5 µg/mL, respectively. In addition, SSLE-AuNPs exerted potent anti-bacterial effect against Staphylococcus aureus (MIC50 68 ± 2.1 μg/mL) and Klebsiella pneumoniae (MIC50 82 ± 2.3 μg/mL), which was comparable to that of the standard antibacterial agent, tetracycline. Moreover, SSLE-AuNPs induced significant reduction in cellular viability of A549 cells at concentrations of 100, 200 and 400 μg/mL, respectively (p < 0.001). Such cytotoxic potential of SSLE-AuNPs was accompanied by considerable instigation of nuclear fragmentation and condensation, caspase activation, and ROS generation in A549 cells. Furthermore, in vitro studies highlighted the anti-inflammatory potential of SSLE-AuNPs on murine alveolar macrophages (J774A.1) via deflating inflammatory mediators such as the proinflammatory cytokines. To sum up, the present findings have substantiated the antioxidant, antibacterial, anticancer and antiphlogistic properties of SSLE-AuNPs, paving the way for subsequent investigations into green synthesized nano-formulations.

Patients with disseminated metastatic disease from breast cancer are likely to have liver involvement in >50% of cases at some point during disease progression. These patients have a poor prognosis; and, when treated with the standard of care systemic therapy they have a median survival of <9-months. Increasing survival in breast cancer patients will likely require the administration of better therapies that are specifically targeted to treat distant metastases. One approach to increasing treatment efficacy for breast cancer liver metastases is through the application locoregional therapies. Locoregional therapies are an appealing interventional approach for breast cancer patients with liver metastases since these tumor lesions are accessible via minimally invasive procedures that can be administered using either ultrasound or CT imaging. Current locoregional therapies to treat breast cancer liver metastases are non-specific and have not produced significant increases in survival. The goal of this study was to design and test a targeted locoregional therapeutic intervention for breast cancer liver metastases. The lead candidate, a fixed-dose small-molecule drug called MBC-005, was tested in vitro and then the efficacy was evaluated in a BALB/c mouse liver metastases model. A novel formulation of N-allyl noroxymorphone hydrochloride incorporated into an alginate-based gel overcomes many of the limitations associated with the administration of small-molecule drugs, which include solubility, off-target toxicity, and enzymatic degradation. In vitro results demonstrated that MBC-005 mediated its anti-tumorigenic effect through a p21-dependent mechanism via a novel molecular pathway, in which N-allyl noroxymorphone component of MBC-005 stimulated the opioid growth factor receptor to increase p21 expression. Intratumoral administration of MBC-005 increased survival 3.9-fold in mice and significantly decreased tumor volume 4-fold. While many cytotoxic therapies increase p21 expression as a response to DNA damage, MBC-005 increased p21 expression independent cytotoxic DNA damage. MBC-005 did not induce off-target toxicity; and, as such, would be amenable to multiple rounds of administration. Nevertheless, it is notable that the positive effects of MBC-005 treatment on increasing survival and decreasing tumor volume in mice was achieved using a single dose.

Despite advancements in treatment for B-cell non-Hodgkin lymphoma (B-NHL) in recent decades, many patients still relapse or are refractory to treatment, which represents a high unmet medical need. Novel CD20 × CD3 T-cell-engaging bispecific antibodies (bsAbs) have created a new paradigm for the treatment of B-NHL. Pivotal studies of four CD20 × CD3 bsAbs, mosunetuzumab, glofitamab, epcoritamab, and odronextamab, as monotherapy, have demonstrated robust responses with generally manageable safety profiles in patients with relapsed or refractory follicular lymphoma and diffuse large B-cell lymphoma after ≥ 2 lines of systemic therapy. These agents have presented unique challenges (e.g., cytokine release syndrome [CRS]), which have required different strategies to overcome. This review provides a comprehensive overview of the clinical development of these four CD20 × CD3 bsAbs that have been investigated for the treatment of B-NHL, with a specific focus on translational assessments to select starting doses in first-in-human studies, management of CRS, application of modeling and simulation approaches to aid dose escalation and optimization/selection, and strategies used in the design of phase I-III clinical trials. By highlighting learnings and experiences from these four bsAbs assessed, which have not been summarized collectively elsewhere, we aim to promote more efficient study design for novel bsAbs in B-NHL in the future.

Lung cancer is a leading cause of cancer deaths worldwide and new therapeutic approaches are needed. This study investigates the efficacy of a new zinc oxide-based nanomedicine in a mouse model of heterotopic lung cancer. C57BL/6 mouse model with Lewis lung carcinoma (LL2) cells was used. The mice were treated with different doses of nanodrug, cisplatin, or phosphate-buffered saline. Tumor growth, metastasis, markers for oxidative stress, and immune responses, in particular the infiltration of CD8+ T cells, were examined. The nanodrug significantly reduced tumor size, inhibited metastasis, and improved survival compared to the control group. Moreover, no significant toxic effect was observed in hematological, biochemical and histopathological analyses. Furthermore, the nanodrug altered the tumor microenvironment in favor of immune system activation by modulating the level of oxidative stress and increasing CD8+ cell infiltration. The results show that this new nanomedicine may be a candidate for an effective treatment for lung cancer.

Alleviating psychological distress in women with breast cancer undergoing treatment is a major worldwide issue. The growing use of new technologies in healthcare to support patients requires a more in-depth appraisal of the optimal methods for delivering these interventions. The present study aims to explore the clinical potential of a 360° video of local landscapes to reduce psychological distress of breast cancer patients receiving intravenous chemotherapy. We presented the same content in two different viewing conditions (immersive vs. non-immersive) in order to isolate the specific effect of immersive technology.

Cyanine dyes usually serve as good fluorescence probes but not as efficient photosensitizers owing to the spin-forbidden intersystem crossing process and short excited-state lifetime. Nevertheless, the structure-derived energy release from the excited state could enable dyes to function efficiently. In this work, we developed cyanine dimers (2o-Cy, 2m-Cy, and 2p-Cy) based on exciton coupling effects by connecting two Cy5.5 molecules at the N-indole site with nonconjugated ortho/meta/para-bis(bromomethyl)benzene linkers. These dimers exhibited significantly enhanced molar extinction coefficients (32-45 × 104 M cm-1) as well as satisfactory triplet excited-state quantum yields (32-44%) and lifetimes (10.6-11.9 μs), leading to a substantially enhanced reactive oxygen species production along with efficient antitumor activity under both normoxic and hypoxic conditions. Furthermore, 2p-Cy NPs ablated primary tumors, inhibited distant tumor growth, and prevented metastatic regrowth via photoinduced innate immune activation. This dimer-based strategy represents a powerful approach to develop high-performance photosensitive dyes for antitumor photodynamic immunotherapy.

Ovarian cancer (OC) is associated with poor prognosis and immune evasion through PD-L1 expression. While anti-PD-L1 therapies have shown limited efficacy, combination strategies may enhance therapeutic outcomes. This study explores the potential of metformin to modulate the immune microenvironment and improve the efficacy of PD-L1 inhibitors in OC. An immunocompetent C57BL/6 mouse model of OC was used to evaluate the effects of metformin and PD-L1 inhibitors on tumor progression, immune cell infiltration, and cytokine expression. Mice received daily metformin treatment for 2 weeks, with PD-L1 inhibitors administered twice weekly. Tumor growth was monitored via volume measurements, immune cell infiltration was assessed by flow cytometry, and cytokine levels (Granzyme B, IFN-γ) were quantified using ELISA. Metformin significantly reduced tumor growth, increased CD8+ T cell infiltration, upregulated RBMS3, and elevated Granzyme B and IFN-γ expression. Additionally, metformin downregulated PD-L1 expression, and its combination with PD-L1 inhibitors further enhanced CD8+ T cell activity. Silencing RBMS3 reversed these effects, underscoring its critical role in immune modulation. These findings suggest that metformin, in combination with PD-L1 inhibitors, may enhance antitumor immune responses and improve treatment outcomes in OC. Targeting RBMS3 could represent a novel therapeutic approach for overcoming immune evasion in OC.

Near infrared (NIR) aggregation-induced emission (AIE)-based luminogens are emerging as powerful materials with significant potential in cancer diagnosis, imaging, and therapy applications. Of precise note are the rapidly progressing areas in the field encompassing deep-tissue imaging, resistance to photobleaching, and biomedicine. Unlike traditional aggregation-caused quenching (ACQ) fluorophores, AIE materials with NIR emissive features can revolutionize the broad transdisciplinary areas of biomedicine, therapy, and healing, making them highly effective for real-time monitoring and healthcare purposes. In this study, we have synthesized a (E)-2-(2-(4'-(2,2-diphenylvinyl)-[1,1'-biphenyl]-4-yl)vinyl)-1,3,3-trimethyl-3H-indol-1-ium, named as 3T, and explored its antiproliferative potential on MCF-7 and MDA-MB-231 breast cancer cells. The 3T molecule exhibited strong near-infrared (NIR) emission ranging from 600 to 800 nm in a 99% water fraction (fw). In silico target prediction and molecular docking identified potential target proteins and assessed their binding interactions and affinities. Further, in vitro studies demonstrated efficient cellular internalization and dose-dependent reduction in cell viability. The IC50 values of 32.26 and 35.75 μM were observed in MCF-7 and MDA-MB-231 cells, respectively. The treatment of 3T generated 2.1- and 1.9-fold increases in reactive oxygen species (ROS) for MCF-7 and MDA-MB-231 cells, respectively, and induced a change in mitochondrial membrane potential, leading to apoptosis, as confirmed by flow cytometry studies. The treatment was also effective for tumor spheroids. Thus, NIR AIEgen 3T offered several distinct advantages such as strong antiproliferative ability, stability, and imaging, positioning it as a potential candidate for cancer therapeutic applications.

Small-molecule targeting of ribonucleic acid (RNA) is a new and promising therapeutic approach, but it requires the discovery of small compounds that can specifically target particular RNA structures. In this context, a comprehensive description of the photophysical interaction features of phenothiazinium dyes such as thionine (TH)/methylene blue (MB) with transfer ribonucleic acid (tRNA) is examined by spectrophotometric titration and molecular docking analysis. After binding with tRNA, TH/MB dyes displayed emission, and absorption characteristics were significantly changed. The observed tRNA-induced spectral alterations are attributed to energy transfer from guanine base pairs, likely resulting from an intercalative interaction mode proposed for tRNA. The negative free energy change value (ΔG = ~ - 27.5 kJ mol-1) of the TH/MB dye-tRNA systems suggests that the present binding interaction is highly favorable and spontaneous. The conformational alterations of the tRNA with both dyes were verified using circular dichroism analyses. Molecular docking test results indicated that TH/MB dye molecules bonded to the tRNA cavity in a specific pattern. The novelty of this study resides in a unique role for TH/MB dyes in tRNA dysfunction, expanding our understanding of how TH/MB dyes and their tRNA complexes were used in in vitro cytotoxic investigations of human lung cancer cells.

In our work, we focused on the development of nanostructured lipid carriers (NLCs) loaded with dexibuprofen (DXI) and their application for cancer therapy by proposing the binding of phospholipids with this non-steroidal anti-inflammatory drug (NSAID) to obtain new delivery systems.

Cisplatin (cis-diamminedichloroplatinum II, CDDP), a widely used chemotherapeutic agent, is clinically limited by nephrotoxicity. Rhein, an anthraquinone from Radix Rhein Et Rhizome, shows nephroprotective potential. This study investigated Rhein's protective effects and mechanisms in CDDP-induced acute kidney injury (AKI).

This study aimed to investigate the pharmacological mechanisms of Shugan Jianpi Formula (SGJPF) in treating TNBC using network pharmacology and molecular biology approaches.

Combination of multiple therapies is a common approach to treating patients with unresectable hepatocellular carcinoma (uHCC). The impact of immune checkpoint inhibitors (ICIs) on prognosis in uHCC patients treated with transarterial chemoembolization (TACE) and lenvatinib remains unclear.

Immune checkpoint inhibitors (ICIs) significantly improve survival in lung cancer patients. However, checkpoint inhibitor pneumonitis (CIP) remains a critical safety concern. This meta-analysis systematically evaluates demographic, clinical, and laboratory risk factors associated with CIP development to guide risk-stratified management.

The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, particularly in lung cancer. However, their use in patients with pre-existing autoimmune diseases (PADs) presents unique challenges. PADs, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and psoriasis, complicate the clinical management of lung cancer due to concerns about worsening autoimmune symptoms during ICI therapy. This review summarized the safety and efficacy of ICIs in lung cancer patients with PAD, focusing on the available clinical evidence, the optimal timing of ICI initiation, and the potential predictive biomarkers for immune-related adverse events (irAEs). Future prospective studies are needed to establish definitive guidelines for the use of ICIs in this population, with a focus on identifying patients at risk, managing ICI resumption after irAE and developing new medications with durable control of both cancer and PAD.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Many researchers have previously reported that natural compounds from plants or Chinese Traditional Herbs have a potential to treat NSCLC. But it has not been reported that phytol can treat NSCLC. In this research, we first exposed this effect on A549 cells and researched the mechanism.

Multimodal tumor therapy based on "all-in-one" nanoplatforms enhances therapeutic efficacy, simplifies the construction process, and improves material utilization. Elemental selenium was successfully supported on upconversion nanoparticles (UCNPs) to constitute the near-infrared (NIR) light-responsive UCNP@Se heterostructures for the first time. Under 980 nm irradiation, the UCNP@Se heterostructures could not only produce holes and superoxide radicals •O2- but also catalyze the generation of hydroxyl radicals •OH by highly elevated levels of H2O2 in tumor cells to kill the tumor cells. In addition to the superior photocatalytic performance, elemental selenium itself also exhibited inherent inhibition activity against tumor cells. On the basis of the binding of anthracycline anticancer drugs such as doxorubicin (DOX) to the supported elemental selenium through Cu2+ bridging coordination, the UCNP@Se-Cu-DOX drug delivery system was constructed. The introduction of Cu2+ not only improved the efficient loading of DOX but also achieved the "AND" logic-controlled release of DOX under the combined stimuli of low pH and overexpressed glutathione (GSH) in tumor cells. Moreover, the loaded Cu2+ reacted with the overexpressed GSH to generate the active species CuII-GSSG upon NIR light irradiation, which further promoted tumor cell apoptosis. The NIR light-responsive UCNP@Se-Cu-DOX drug delivery system achieved the combination tumor therapy of selenium therapy, photocatalytic therapy, and logic-gated chemotherapy and has great potential applications in tumor therapy.