P2, N=30, Recruiting, University of California, Davis | Not yet recruiting --> Recruiting

P1, N=20, Recruiting, Children's Hospital Medical Center, Cincinnati

In conclusion, PBM modulated the response of SaOs-2 osteoblastic cells treated with ZA in a wavelength- and dose-dependent manner. PBM at 808 nm and 1 J stimulated cell metabolic activity and upregulated BCL-2 expression, suggesting a potential protective effect against ZA-induced cytotoxicity.

Ocriplasmin and pamidronate were identified as potential therapeutics. Our findings highlight the therapeutic relevance of these hub genes and identify them as potential drug targets and prognostic biomarkers in ovarian cancer.

Zoledronate upregulates TLR4 expression in neutrophils and keratinocytes and augments LPS-induced inflammation, suggesting a mechanism by which BPs exacerbate oral inflammatory responses. These findings provide new insight into the pathogenesis of BRONJ and suggest that targeting TLR4 signaling may be a potential strategy to mitigate BP-associated oral complications.

Suppressing bone remodeling with zoledronate or targeting macrophage-associated niche factors mitigated clonal development. Collectively, our study reveals a previously unrecognized inflammatory landscape shaped by local bone remodeling. The finding presents targetable mechanisms and warrants further studies on the use and precautions of bone-modulating management in clonal blood disorders.

To address this limitation, a multifunctional nanomedicine (PM-DPA/R848) was developed by loading the TLR7/8 agonist resiquimod (R848) into a nanocarrier composed of poly(L-methionine) (PM) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-poly(ethylene glycol)-alendronate (DSPE-PEG-ALN, DPA)...Moreover, DPA enhances intratumoral drug accumulation in vivo, and PM-DPA/R848 achieves a 77 % tumor suppression rate. Thus, PM-DPA/R848 acts as a precision nanoformulation that synergistically suppresses M2 macrophages and promotes M1 polarization, providing a promising strategy for osteosarcoma immunotherapy.

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.