However, conventional ex vivo expansion protocols using zoledronic acid (Zol) and IL-2 often lead to terminal differentiation and diminished effector function. In orthotopic tumor models, γδ2 T-Da cells enhanced tumor control, reduced TNBC metastasis, and prolonged survival of GBM-bearing mice. These results suggest that dasatinib improves γδ T cell yield and function, providing a practical and translatable strategy for optimizing γδ T cell-based adoptive therapy, particularly for solid tumors.Trial registration: Trial number: CMUH111-REC3-185.

P1/2, N=12, Active, not recruiting, Dextech Medical AB | Recruiting --> Active, not recruiting

The ATMP was manufactured and validated in a GMP facility and was obtained from leukapheresis stimulated with zoledronic acid and IL-2, afterward depleted of αβ T lymphocytes using the CliniMACS Prodigy...Furthermore, γδ T lymphocytes and NK cells were cytotoxic against myeloid leukemia or neuroblastoma cells. In conclusion, we implemented a novel ATMP to be shortly translated into clinical practice, which may be used in the post-transplant phase as efficacious immunotherapy in neuroblastoma and leukemic pediatric patients.

Simulated treatment of bone-adapted tumors with the bisphosphonate zoledronic acid stabilizes bone density but has limited or highly variable effects on tumor growth. These results suggest that OC inhibition alone may be insufficient to restrain tumor expansion once tumors have adapted to the bone microenvironment. Together, these findings support the hypothesis that tumor adaptation to the bone microenvironment governs dependence on bone-derived growth factors and response to OC-targeted therapy, underscoring the value of mechanistic modeling for elucidating tumor-bone interactions and guiding tumor-type-specific treatment strategies for TIBD.

In this study, we evaluated the impact of human serum on the expansion, phenotype, function, and transcriptomic landscape of Vγ9Vδ2 γδ T cells cultured with zoledronate and cytokines under serum-free versus serum-containing conditions...Furthermore, re-exposure to serum late in culture had minimal influence on γδ T cell functionality. These findings demonstrate the feasibility and advantages of serum-free expansion protocols for Vγ9Vδ2 γδ T cells, offering improved consistency, safety, and therapeutic potential.

However, there was no significant difference in Cy5.5 signal between Lip-Cy5.5-Aln and control in bone-forming C4-2B-BMP4 tumors, nor was localization greater in osteoblastic versus non-osteoblastic tumors. Overall, the alendronate-conjugated liposome showed enhanced musculoskeletal accumulation, but it does not seem to effectively target pathologic intratumor bone formation in metastatic prostate cancer.

Notably, zoledronate-expanded Vγ9Vδ2 γδ T-cell lines achieved cytotoxicity comparable to PHA-expanded αβ cells. Together, these in vitro data reveal subset-specific BLN responses and support the hypothesis that ex vivo-expanded Vγ9Vδ2 γδ T cells could complement BLN-mediated cytotoxicity, particularly under conditions of higher CD19 density and lower target burden. These findings provide a mechanistic framework for future testing of γδ T-cell/BLN combination strategies in patient-derived models and clinical studies.

Osteoporosis is common in postmenopausal women due to reduced estrogen levels and leads to weaker bones. Alendronate is widely prescribed to lower fracture risk, but it may interfere with bone healing after dental procedures such as tooth extraction. Using a rat model that mimics postmenopausal bone loss, this study examined how estrogen deficiency, alendronate treatment, and estrogen replacement together influence healing of the tooth socket, a process highly relevant to periodontal and oral surgical care. The results showed that estrogen deficiency alone already compromised bone repair, and this effect became more pronounced when alendronate was used. Estrogen replacement with estradiol valerate did not fully restore normal healing, but it reduced several harmful changes in bone structure and local inflammatory activity associated with alendronate. Importantly, no bone necrosis was observed under the conditions studied, although persistent disturbances in bone remodeling were evident. These findings help clarify how systemic bone conditions and osteoporosis treatments can influence periodontal wound healing and support more informed risk assessment and interdisciplinary planning when dental extractions are required in patients with osteoporosis.

In this study, we develop β-tricalcium phosphate (β-TCP) granules decorated with selenium (Se)-doped mesoporous silica nanoparticles (SeMIA@TCP), in which nanoparticles are functionalized with imine bonds for acidic pH-responsive detachment and alendronate for strong β-TCP binding...Furthermore, the released nanoparticles enhanced alkaline phosphatase (ALP) expression and mineralization in hMSCs, underscoring their osteogenic potential. Collectively, these results demonstrate the potential of tumor microenvironment-responsive Se-doped MSN-assembled TCP granules as a design platform for bifunctional scaffolds in bone cancer treatment.

Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11-ERLIN1 interaction and restoring cholesterol homeostasis. ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11-ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

P=N/A, N=0, Withdrawn, University Hospital, Rouen | N=72 --> 0 | Not yet recruiting --> Withdrawn

Pamidronate (APD), a nitrogen-containing bisphosphonate, has shown potential in managing osteolytic lesions by inhibiting osteoclast activity...Moreover, CHA exhibited excellent biocompatibility with no observed systemic toxicity. These results underscore the promise of CHA as a clinically translatable therapeutic strategy for the treatment of osteolytic bone metastases.