In this study, we investigated the potential of the antihistamine ketotifen to remodel the TME and enhance intratumoral delivery and efficacy of liposomal therapeutics, PEGylated liposomal doxorubicin (Doxil), and a co-encapsulated alendronate-doxorubicin (PLAD) formulation. Random forest analysis identified tumor stiffness, IL-10, and TNF-α as the strongest predictors of therapeutic outcome. These findings demonstrate that microenvironmental modulation by repurposing ketotifen improves nanomedicine delivery and efficacy in PDAC.

Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, is widely used to treat osteoporosis and bone metastases. The antioxidant N-acetylcysteine (NAC) similarly reduced ZA-induced ROS and p-TBK1 levels and improved cell growth, although it had limited effects on p-PKB at 8 h. Importantly, delayed PDRN treatment following ZA exposure reversed ZA-induced cell growth inhibition and TBK1 activation in a dose- and time-dependent manner. In summary, these findings demonstrate that ZA suppresses HGF-1 cell growth through ROS production, TBK1 activation, and inhibition of PKB and STAT-3, whereas PDRN counteracts these effects primarily by suppressing TBK1 activation and oxidative stress.

We combine an innate cell-enriched product activated by interleukin-2 (IL-2) and zoledronic acid (ZA) (ICPIL2ZA) with low-dose radiotherapy (RT) and monoclonal antibodies (mAbs) to overcome this immunosuppressive TME...RT amplifies ICPIL2ZA effectiveness by inducing NKG2D ligands on tumor cells, facilitating immune infiltration that leads to tumor growth control and extends survival without apparent toxicity. These results suggest that ICPIL2ZA can overcome limitations of traditional therapies by augmenting antitumor capabilities of endogenous immune cells, highlighting a promising autologous strategy for PDAC and other immunologically "cold" tumors.

P1, N=4, Terminated, University of Calgary | N=56 --> 4 | Trial completion date: Dec 2024 --> Jul 2025 | Recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Jul 2025; Recruitment stopped due to funding shortage. The scope of the original study increased beyond what had been budgeted in the grant that funded it, and follow-up funding attempts were not successful.

Patients with abnormal renal function, BRCA1 mutations, or those at high risk of developing skeletal-related events may benefit from denosumab over zoledronic acid. During denosumab treatment in patients with renal dysfunction, attention should be paid to the occurrence of hypocalcemia.

The patient was started on a low phosphate diet, sevelamer, and acetazolamide and was instructed to avoid calcium and vitamin D supplements. Intravenous Zoledronic Acid was also given. The patient reported improvement in his symptoms in the follow-up visits.

LC-MS showed that 6-FM-treated CHO-K1 cells accumulated substantial MPP while risedronate, an inhibitor of farnesyl diphosphate synthase, primarily increased DMAPP/IPP...Both BTN2A1 + BTN3A3-transfected CHO-K1 cells and BTN3A1 knockout K562 cells could detect 6-FM, despite their absence of BTN3A1. Our findings provide evidence that MPP functions as a natural ligand of BTN3A3 and establish a foundation for elucidating biological functions of BTN3A3 complementary to the established BTN3A1 pathway.

Drug sensitivity analysis demonstrated a correlation between LGALS1 expression and the response to agents such as zoledronate and staurosporine. Immune- and lipid metabolism-related genes contribute to macrophage polarization and are closely linked to GBM prognosis. The identified gene signature provides prognostic value and potential therapeutic targets for immunometabolic modulation in GBM.

We specifically engineer these CAFs in situ to enhance antitumor immunity using an innovative nanodrug, IL-15 plasmid-loaded FAP-sensitive MgCa/z-Gly-Pro-pamidronate acid nanoparticles (PN/MCG NPs)...Furthermore, we also prove that FAP+ αSMA+ human mammary fibroblast cells (FAP+ αSMA+ HMFs) also can be engineered by PN/MCG NPs in vitro. Our findings demonstrate that in situ CAF engineering is a promising strategy to remodel the tumor microenvironment and enhance immunotherapy in TNBC.

Recent advances in γδ T cell-based immunotherapies, particularly in combination with agents such as zoledronate bisphosphonate that enhances tumor recognition, show promising preclinical results. However, obstacles such as the suppressive tumor microenvironment and immune evasion mechanisms remain significant. This chapter highlights the therapeutic potential of γδ T cells in prostate cancer and the need for further research to optimize these approaches.

Tumor suppression by anti-neu antibody is associated with MDSC reduction via inhibition of key MDSC-related factors. MDSCs may be a therapeutic target to enhance Herceptin efficacy in breast cancer.

P1, N=22, Recruiting, University of Wisconsin, Madison | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2026