Mechanistically, we demonstrated that TMEM158 positively regulates ABCG2 expression, which consequently contributes to drug resistance. In summary, we identified cfRNA TMEM158 as a potential diagnostic biomarker for ovarian cancer and elucidated the critical involvement of TMEM158-ABCG2 signaling axis in the development of doxorubicin resistance.

To address this issue, we developed a supramolecular self-assembled codelivery nanoprodrug (DOX@C18Fc-Q[7] NPs) composed of ferrocene (Fc)-based supramolecular amphiphiles (C18Fc-Q[7]) and a nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) activator (doxorubicin, DOX)...Moreover, DOX induces cell death through apoptosis, providing a synergistic effect to further enhance the ferroptosis therapy. In vivo studies have demonstrated that this enhanced ferroptosis therapy effectively inhibits tumor growth and metastasis while maintaining good biosafety.

CASC9, as an oncogenic lncRNA, has a promotional effect on Dox resistance and PTC progression via miR-28-3p/BCL-2 axis and PI3K/AKT signaling pathway.

This system used carboxymethyl dextran (CMD) and Black Hole Quencher 3 (BHQ3) to encapsulate PTL and the cytotoxic drug doxorubicin (DOX) within a red blood cell membrane (RBCm), enhancing stability and biocompatibility while allowing gradual drug release under hypoxic conditions...This inhibitory effect is closely associated with the Hippo/YAP1/SOX9 pathway. This study highlights the effectiveness of the pH-responsive biomimetic nanoparticle system CMD-BHQ3-PTL/DOX@RBCm in delivering PTL to tumor sites, with SOX9 and its upstream Hippo/YAP1 pathway playing a critical role in the underlying mechanism.

MD consists of a core-layer structure, a manganese dioxide (MnO2) core, and a cross-linked layer with bovine serum albumin (BSA) and doxorubicin (DOX), with a specific ratio of DOX to manganese...Moreover, it induces distinct cytotoxicity in cancer cells through apoptosis and cGAS-STING activation, leading to increased calreticulin expression and enhanced DC phagocytosis. Consequently, it results in superior tumor suppression and prolonged survival with the high accumulation of MD in the tumor and no observed systemic toxicities, highlighting its potential as a therapeutic agent in cancer treatments.

In conclusion, following parameter optimization, LIPUS-MB was found to reduce the drug resistance of MDA-MB-231/DOX cells. The underlying mechanism may involve the downregulation of P-gp and ABCG2 proteins expression through the modulation of the JNK/c-Jun pathway by LIPUS-MB, thereby inhibiting cell proliferation activity and promoting apoptosis, and enhancing the in vivo anti-tumor effect of DOX, thus reversing multidrug resistance in triple-negative breast cancer.

Furthermore, treatment of OSCs with cisplatin (CIS) or doxorubicin (DOX) resulted in preserved mitochondrial morphological stability, which was not observed in non‑OSCs. These findings unveil a novel mechanism underlying chemoresistance in osteosarcoma and suggest that targeting DRP1 could be a promising therapeutic strategy to overcome chemoresistance in OSCs. This provided valuable insights for enhancing treatment outcomes among patients with osteosarcoma.

In this study, we developed a graphene-based lipid modulation nanoplatform (NSD) that carries SB-204990, a small molecule inhibitor specific for ATP citrate lyase (ACLY), and doxorubicin (DOX), a chemotherapeutic agent, and the trio enables synergistic treatment of OSCC with lipid starvation, chemotherapy, and photothermal therapy...The changes in tumor cell lipid levels and cell proliferation arrest induced by ACLY inhibition suggest that ACLY may be a promising target for lipid starvation therapy and resistance to chemoresistance, and its inhibitors are expected to become new anticancer drugs. The NSD nanocarrier system enables synergistic treatment with lipid starvation, chemotherapy, and photothermal therapy, which represents an innovative approach to combating tumors.

The tumor exhibits a poor response to conventional chemotherapy and has a poor prognosis; therefore, correct diagnosis is necessary. Moreover, new therapies such as EZH2 inhibitors and etoposide should be considered in cases where conventional chemotherapy is ineffective.

Amidst this context, the present investigation delineates the synergistic potentiation of doxorubicin (DOX)-a canonical chemotherapeutic-by Ursodeoxycholic acid (UDCA), a compound with a historical pedigree in hepatobiliary medicine, now repositioned within oncological pharmacotherapy due to its dichotomous cellular modulation-affording cytoprotection to non-malignant epithelia whilst eliciting apoptotic cascades in neoplastic counterparts. The implications of this research are twofold: firstly, it offers a compelling evidence base for the clinical reevaluation of UDCA in combinatory chemotherapeutic regimens; secondly, it posits a novel mechanistic insight into the modulation of chemotherapeutic efficacy and resistance. Collectively, these insights advocate for the expedited clinical translation of UDCA-DOX synergy, potentially heralding a paradigm shift in the management of NSCLC, thereby addressing a critical lacuna in contemporary oncological therapy.

The combination of mitoxantrone (MTX) and curcumin (Cur) optimized ICD properties in TC-1 tumor cells, as evidenced by increased release of "find me" signals, such as HMGB1 and ATP, and enhanced exposure of the "eat me" signal, CALR, compared to either MTX or Cur alone...Furthermore, the ICD cells in combination with E7-HBcAg VLPs or E7-Q11 nanofibers induced more intense effector cell responses to the antigen included in the nanovaccines, as well as a broad spectrum of antigens provided by tumor cells, and significantly suppressed the growth of established tumors compared with either ICD cells, VLPs, or nanofibers alone. In conclusion, the combination of ICD cells and nanosized antigens produced synergistic antitumor effects and elicited robust and comprehensive antitumor immunity, presenting an attractive strategy for developing personalized tumor vaccines.

In this chapter, we provide straightforward methodologies to isolate DCs from murine bone marrow (bone marrow-derived DCs, BMDCs), induce immunogenic apoptosis in murine MCA205 fibrosarcoma cells using ICD inducer mitoxantrone (MTX), co-cultivate BMDCs with the MTX-treated cancer cells, and to assess the activation and maturation status of BMDCs by flow cytometric-assisted quantification of co-stimulatory molecules (MHC II, CD86, CD80) expressed on the plasma membrane of BMDCs. With minor adjustments, the same protocol can be implemented to other cancer cell lines or to analyze the phenotypic status of non-professional APCs.

As mentioned above, there is no established treatment regime for esophageal NEC, and the benefits of conversion surgery are unknown. Our patient achieved long-term recurrence-free survival after radiation therapy, chemotherapy, and surgery for an esophageal NEC with left atrial invasion and multiple lymph node metastases. Conversion surgery for esophageal NECs that respond to chemotherapy may contribute to long-term survival.

Also, we utilized epirubicin-sensitive (parental) and rpirubicin-resistant (EPIR) breast cancer cell lines to explore the role of RHAMMM in breast cancer progression...In addition, the knockdown of RHAMM significantly altered the expression of N-cadherin and E-cadherin, leading to an epithelial phenotype. Aberrant RHAMM signaling were considered to cause chemoresistance related to cancer stemness and epithelial to mesenchymal transition, and increased cell proliferation and migration of both chemo-sensitive and chemo-resistant breast cancer cells.

No abstract available

RNA pull-down, RNA immunoprecipitation (RIP), and actinomycin D experiments were performed to investigate the relationships between SRSF9 and USP22...SRSF9 enhanced the malignant characteristics of OC through a positive feedback loop of SRSF9/USP22/ZEB1. This functional circuit may help in the development of novel therapeutic approaches for treating OC.

Loading the hydrogel with mitoxantrone (MTX) and metformin (MET) further enhances the therapeutic effect by combining chemotherapy with PD-L1 downregulation. Mechanistically, KFM promotes PD-L1 degradation via a ubiquitin-dependent pathway. This "carrier-free" delivery system expands the role of supramolecular hydrogels beyond passive carriers to active immunotherapeutic agents, offering a promising new strategy for cancer therapy.

DCM mice were established by induction with doxorubicin and then treated with melatonin...Furthermore, melatonin-treated DCM mice displayed lower serum and cardiac levels of IL-1β, IL-6, and TNF-α, as well as higher numbers of M2-type macrophages in cardiac tissue, indicating that melatonin treatment could decrease inflammatory responses and facilitate M2 macrophage polarization in DCM mice. Thus, melatonin treatment alleviated cardiac dysfunction and inflammatory responses by promoting M2 macrophage polarization in the DCM mouse model.

Subsequently, large numbers of electro-active monomers N-acryloxysuccinimide (NAS) were successfully grafted to the electrode surface via PET-RAFT reaction, which provided plenty of junction sites for doxorubicin-polycaprolactone (Dox-PCL) synthesized by ROP...Under optimized conditions, the biosensor has a wide linear detection range of 0.1 pM to 1 μM, with a detection limit of 86.9 fM. Attribute to its high sensitivity, specificity, reproducibility and stability, this biosensor possesses considerable potential in early diagnosis of disease and biomedical research.

TRAF6 mRNA stability was tested using actinomycin D treatment...Meanwhile, ELAVL1 knockdown relieved caerulein-induced AR42J cell injury and macrophage M1 polarization, while these effects were abolished by TRAF6 overexpression. TRAF6, stabilized by ELAVL1, promoted caerulein-induced AR42J cell injury and macrophage M1 polarization, suggesting that it might accelerate AP9 progression.

In this investigation, the treatment with solasodine and doxorubicin combination showed a notable increase in intracellular ROS generation in KBChR-8-5 cells...Additionally, the combination therapy increased the lipid peroxidation levels while simultaneously reducing the activities of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the levels of glutathione (GSH). These results demonstrated that solasodine disrupts redox balance, and overcomes drug resistance by downregulating P-gp via regulating Nrf2/Keap1 signaling pathway in MDR cancer cells.

The PPy microspheres provided a larger surface area for gold nanoparticle (Au NP), CA125 antibody and signal molecule adriamycin immobilization...Under optimal conditions, the immunosensor showed a wide linear response range of 10-100 U mL-1 with a detection limit of 2.4 μU mL-1 (at 3σ/N), and recovery was 98.1-101.2%, as evaluated using human serum samples. Furthermore, the immunosensor was applied to measure real serum samples, and the results obtained were in accordance with those of enzyme-linked immunosorbent assay (ELISA), indicating that the proposed immunosensor is an ideal platform for clinical diagnosis application.

P=N/A, N=112, Active, not recruiting, Jazz Pharmaceuticals | Recruiting --> Active, not recruiting

P2, N=40, Not yet recruiting, Case Comprehensive Cancer Center | Initiation date: Aug 2024 --> Mar 2025

P4, N=354, Completed, Huashan Hospital | Trial completion date: Nov 2023 --> Aug 2024 | Trial primary completion date: May 2023 --> Aug 2024 | Active, not recruiting --> Completed

P3, N=60, Completed, Federico II University

P=N/A, N=70, Not yet recruiting, Beijing Friendship Hospital Pinggu Campus,Capital Medical University; Beijing Friendship Hospital Pinggu Campus,Capital Medical University

P=N/A, N=5, Completed, Lishui Central Hospital; Lishui Central Hospital

P=N/A, N=114, Recruiting, Army Medical Center of PLA; Army Medical Center of PLA

P4, N=40, Not yet recruiting, General Hospital of Chinese People's Liberation Army Northern Theater Command; General Hospital of Chinese People's Liberation Army Northern Theater C

Simultaneously, the elevation of GSTP1 and JNK complex may reduce the expression of p-JNK and inhibit the activation of JNK pathway, which might inhibit cell apoptosis. In conclusion, our experiments suggested that upregulated SPAG6 might mitigate the pro-apoptotic effects of DNR through ROS/JNK MAPK axis in a GSTP1-dependent manner.

Here, we found that doxorubicin (DOX) induced an increase of labile Zn2+ in lung cancer cells, and these labile Zn2+ protected tumor cells against DOX cytotoxicity...Finally, the results unraveled that nanosized TPEN at low dose endowed DOX with the killing ability on resistant tumor cells. Taken together, our results demonstrate that chelating drug-induced labile Zn2+ by nanosized TPEN at low dose enhances lung cancer chemotherapy by inhibiting ABCB1, providing a feasible strategy to overcome chemoresistance in lung cancer.

The synthesized pyrazolo pyrimidine derivatives showed potential as lead compounds for further development due to their promising binding affinities and significant anticancer activity, particularly those with nitro and heterocyclic moieties.

This study demonstrated that simultaneous administration of CBD and DOX can increase antitumoral effect and reduce DOX cardiotoxicity. Nevertheless, CBD can induce cardiotoxicity as administrated alone.

There is considerable controversy over whether it should be managed as small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC). Therefore, in order to solve the problem of confusion in the selection of treatment regimens for CLCNEC, while also considering the therapeutic effects, this article summarizes and analyzes previous studies, fully seeks evidence, and boldly proposes new therapeutic insights: the etoposide-platinum (EP) regimen serves as the basis for adjuvant therapy; In addition, SCLC/NSCLC-CLCNEC can be distinguished based on presence of RB1 and TP53 co-mutation, and targeted therapy or NSCLC type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) can be used in combination or sequentially for NSCLC-CLCNEC.

P3, N=882, Recruiting, University of Ulm | Trial completion date: Mar 2024 --> Jun 2027 | Trial primary completion date: Mar 2024 --> Jun 2027

Recognising that the co-delivery of multiple drugs can enhance treatment efficacy while reducing systemic toxicity and drug resistance, three additional classes of nanoparticles were developed by adding doxorubicin and resveratrol to the chitosan-PLGA-miRNA-34a core...Cells were treated in both two-dimensional cultures and three-dimensional osteosarcoma spheroids, creating a biomimetic cellular model. Increased apoptotic activity and disruption of cellular functions were primarily observed with nanoparticles co-delivering miRNA-34a and drugs, particularly those functionalised with the LbL nanocoating, as confirmed by PCR analysis.

Importantly, systemic administration of NBA significantly enhances the chemo-immunotherapy of B16-F10 melanoma-bearing mice pretreated with doxorubicin by reversing the immunosuppressive tumor microenvironment. Furthermore, NBA carrying ovalbumin and B16-F10 cell lysates induces robust OVA-IgG antibody production and effectively inhibit tumor growth, respectively. The artificial nanobacteria hold great promise as a potent systemic immunoadjuvant for cancer immunotherapy.

Moreover, in a murine breast cancer model, the nanocascades of glucose oxidase and catalase inhibited tumor progression and enhanced the therapeutic efficacy of doxorubicin. The prolonged circulation and promoted reaction efficacy of these nanocascades underscore their substantial potential in enzyme replacement therapy and the treatment of various diseases.

These potent MDR1 inhibitors were found to enhance chemosensitivity to doxorubicin in MDR1-overexpressing cells...Furthermore, the total number of methoxy groups in the flavonol backbone was found to be a significant factor in determining the potency of MDR1 inhibition. These observations provide fundamental insights into the structure-activity relationship between flavonol derivatives and MDR1 inhibition, potentially aiding in overcoming drug resistance in cancer.

P3, N=90, Recruiting, GlaxoSmithKline | Not yet recruiting --> Recruiting

BL cells overexpressing miR-525-5p were treated with phorbol 12-myristate 13-acetate (PMA), and Hoechst 33258 staining and Calcein AM/EthD-I staining were used to analyze the changes in chemotherapy sensitivity of BL cells to doxorubicin (DOX)...PMA treatment reactivated the NF-κB pathway and reversed apoptosis mediated by miR-525-5p overexpression. These findings revealed that miR-525-5p acts as a tumor suppressor, targeting MyD88 to modulate proliferation, cell cycle progression, and apoptosis in BL cells by regulation of NF-κB signaling pathway.