No abstract available

P2, N=60, Completed, Columbia University | Recruiting --> Completed

Ibandronate sodium demonstrates a protective effect on articular chondrocytes and exhibits the potential to decelerate the pathological progression of knee osteoarthritis (KOA) in rats. This mechanism is likely achieved through the inhibition of the TLRs/MyD88/NF-κB signaling pathway.

The radiolabeled complex exhibited a higher rate of cell incorporation to U2OS cells compared to Reduced/Hydrolyzed TcO -. The newly produced radiopharmaceutical is very promising according to the results of in vitro cell culture, HA binding, and quality studies, and will be a step forward for further studies in nuclear medicine for bone cancer diagnostics.

The ligands used were raloxifene, simvastatin, dexamethasone, risedronate, ibandronate, zoledronic acid, ascorbic acid, alendronate, and β-glycerophosphate, whereas the target proteins used were RET, fibroblast growth factor receptor 1, KIT, PDGFRA, VEGFR1, and VEGFR2. Most types of interactions were hydrophobically followed by hydrogen bonding. The current study suggests that raloxifene, simvastatin, and dexamethasone have the potential to act as multitarget inhibitors for osteosarcoma with the ability to induce bone remodeling.

In postmenopausal women with ER+ breast cancer, adjuvant ibandronate 50 mg once daily does not improve DFS and should not be recommended as part of standard treatment regimens.

Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities. The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. The NHS PREDICT tool provides estimates of the benefit of adjuvant bisphosphonate therapy and may aid in decision making. Factors influencing the decision to recommend adjuvant bisphosphonate use should include patients' risk of recurrence, risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy. When an adjuvant bisphosphonate is used to prevent breast cancer recurrence, the therapeutic options recommended by the Panel include oral clodronate, oral ibandronate, and intravenous zoledronic acid. The Panel supports starting bisphosphonate therapy early, consistent with the points outlined in the parent CCO-ASCO guideline; this is a consensus recommendation. The Panel does not recommend adjuvant denosumab to prevent breast cancer recurrence, because studies did not show a consistent reduction of breast cancer recurrence in any subset of those with early-stage breast cancer.Additional information can be found at www.asco.org/breast-cancer-guideline.

Our results suggest that moderate to high TGIF expression is a common feature of breast cancer cells and that this is not associated with bone metastases as first site of relapse. However, a reduced expression is linked to tumor progression, especially in HER2-negative breast cancer.

P3, N=6097, Completed, Southwest Oncology Group | Active, not recruiting --> Completed

It is upregulated upon treatment with zoledronate and this effect reduces invasion of breast cancer cells. In our recent work, we demonstrated that the syndecan-4 level was reduced after trastuzumab treatment. Similarly, syndecan-4 levels are also reduced after panitumumab treatment. Together, the data found suggest that syndecan-4 level is crucial for understanding the changes involving in malignant transformation, and also demonstrate that syndecan-4 emerges as an important target for cancer therapy and diagnosis.

Unlike most conventional CD4 αβ T cells, CD4 Vγ9Vδ2 T cells are potently cytotoxic and can kill cancer cells, which is here shown by the killing of cancer cell lines of different histological origins, including breast cancer, prostate cancer and melanoma cell lines, upon treatment with zoledronic acid. Notably, the killing capacity of CD4 Vγ9Vδ2 T cells correlates with co-expression of CD56.

Further, we designed a risk score with TGF-β1, TNF-α, and IFN-γ levels, which could prognosticate patients for PFS. In conclusion, serum cytokine level, such as TGF-β1, TNF-α, and IFN-γ, could be a potential prognostic biomarker for breast cancer patients with bone metastasis treated with ZA and taxane-based chemotherapy.

Finally, drug prediction analysis showed that zoledronic acid (ZA)-TNFRSF11B was the unique drug-gene relation in both two databases. Methylation-driven gene TNFRSF12A might participate in the development of GBM via response to the TNF biological process and TNF signaling pathway and significantly associated with prognosis. ZA that targets TNFRSF11B expression might be a potential effective drug for clinical treatment of GBM.

The maintenance treatment with IL2 and Zoledronate has a modest activity in myeloma patients after autologous bone marrow transplantation. 2013-001188-22.

Our study has shown that a combination of LTZ and ZLA enhanced apoptosis and inhibited growth of both breast cancer cell lines. This combination can be used to maintain bone integrity in women with breast cancer.

Addition of ZOL to neoadjuvant therapy did not significantly affect clinical outcomes in the overall study population but was associated with increased extra-skeletal recurrence and a trend towards worse survival in ER+/HER2- patients younger than age 45. These findings suggest caution when using zoledronic acid in young, premenopausal women with locally advanced breast cancer and warrant further investigation. Clinical Trial Registration Number NCT00242203, Date of Registration: 10/17/2005.

BP application leads to a systemic pro-inflammatory situation in vivo, independent of surgical trauma, as evidenced by the shift in macrophage polarization towards M1 in various somatic tissues. This provides a possible explanation for the clinically observed anti-tumor effect of bisphosphonates and might also contribute to pathogenesis of MRONJ.

He was treated with aggressive hydration, 4mg of zometa, 30mg of sensipar and two doses of 200mg calcitonin, with improvement in his calcium levels. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021.

Biological and histopathological techniques identified osteoclasts and macrophages as targets of zoledronic acid (ZA), a therapeutic agent that was detrimental for patients in the French OS2006 trial...Multiplex immunohistochemistry demonstrated remarkable bipotent CD68+/CD163+ macrophages, homogeneously distributed throughout OS regions, aside osteoclasts (CD68+/CD163-) mostly residing in osteolytic territories and osteoid-matrix-associated CD68-/CD163+ macrophages. We demonstrate that ZA not only acts on harmful osteoclasts but also on protective macrophages, and hypothesize that the bipotent CD68+/CD163+ macrophages might present novel therapeutic targets.

We determined risk factors for SREs in patients with bone metastasis from breast cancer.

All study feasibility endpoints were met in this trial comparing alternative schedules for adjuvant zoledronate. We will now seek funding for performing a larger efficacy trial.Trial registration: NCT03664687.

The TCRαβ and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL-2...Fas-L highly expressed cancer cells xenotrasplanted 2weeks ago were resistant to TCRαβ-CD8-γδ T cells injection. These results suggested that the apoptosis of Fas-positive TCRαβ-CD8-γδ T cells may be induced by a Fas-mediated signal after interacting with Fas-L-positive cancer cells.

After 5 sessions of irradiation with 20 Gy at the Th8-L1 level, combined Bev and PTX plus zoledronic acid was administered. After 3 balloon dilatations, her condition improved, and oral ingestion was possible. The esophageal stenosis might have been caused by the exacerbation of esophagitis because of the delayed wound healing effect of Bev in addition to radiation.

He needed a dose of zoledronic acid to control hypercalcemia with good results. Despite the unfavorable prognosis associated with the diagnosis of adult T-cell lymphoma / leukemia, treatment with Interferon alfa and zidovudine, when tolerated, can bring good results of disease-free survival, especially in the chronic form.

Faced with the diagnosis of AL amyloidosis, the patient underwent chemotherapy due to spinal infiltration greater than 10% of plasmocytes in bone marrow biopsy, having adopted Bortezomib, Cyclophosphamide and Dexamethasone, in addition to monthly zoledronic acid as a protocol...It is reinforced with the case that the diagnosis of amyloidosis in late stages already with cardiac dysfunction limits the treatment with worsening of the outcome. The characteristic skin lesions must be remembered in order to provide an early diagnosis.

After 4 months of treatment with a CTD regimen plus zoledronic acid, he achieved a VGPR according to the IMWG criteria...He received 1 year of Thalidomide as maintenance therapy...The disease relapsed 7 months after ASCT, during the maintenance therapy with Bortezomib...In addition, the absence of CD27 expression has been considered to be associated with disease progression. It is important to consider these phenotypic characteristics in order to better recognize and elucidate the pathophysiology of MPE in prospective studies.

Moreover, FST -hFc increased body weight in the face of tumor progression (14% increase vs. vehicle), and ActRIIA-mFc reduced the number of lung metastases when combined with bisphosphonate. The present study demonstrates a novel approach to treating osteosarcoma and encourages further investigation of inhibition of the activin receptor signaling pathway as an intervention against the disease.

Promising results are reported on the treatment of various malignancies with in vivo expansion of autologous γδ T cells using zoledronic acid (zol) and IL-2...In vitro real-time cytotoxicity analysis showed that expanded, previously cryopreserved, γδ T cells were effective in killing target cells. Our results demonstrate that large scale ex vivo expansion of donor-derived γδ T cells can be achieved with the use of CD3/CD137L/CD28/IL15RA quadruplet aAPC and zol/IL-2 for clinical application as promising antineoplastic immunotherapy.

Here we present the first reported case of hypercalcemia as a result of immune checkpoint inhibitors Case Description A 68-year old man with metastatic renal cell carcinoma underwent right nephrectomy followed by immunotherapy with ipilimumab and nivolumab...He received fluids, calcitonin and Zoledronic acid...Patient was started on prednisone 1mg/kg/d...Repeat 1,25 dihydroxy vitamin D and CRP levels were back to normal Discussion Hypercalcemia related to checkpoint inhibitors was previously described in setting of increased PTrP. Our patient had hypercalcemia directly related to immunotherapy likely through increased alpha hydroxylation.

However, the efficacy of targeting c-Met in bone metastatic disease, including in RCC, has not been proven. Therefore, further investigation is required focusing the particular role of HGF/c-Met pathway in bone microenvironment (BME) and how to effectively target this pathway in the context of bone metastatic disease.

AP-002 caused these inhibitory effects without causing osteoclast cell death, which was in contrast to zoledronic acid controls. AP-002 promotes osteogenesis in this therapeutic window, while blocking osteoclast development. We therefore conclude that AP-002 has potential as a new anti-bone resorption agent, with a mechanism of action different compared with other currently marketed anti-bone resorption agents.

Zoledronic acid successfully induced apoptosis and reduced various angiogenic cytokine production in hormone-refractory prostate cancer cell lines. Novel treatment protocols may be developed in the future with chemotherapeutic combinations for the treatment of prostate cancer.

Furthermore, in ovarian cancer patients, high PDGFA expression correlated with worse outcomes. Here, it is shown that the adrenergic regulation of macrophages and PDGFA might play a role in ovarian cancer progression.

Although autologous Vγ9Vδ2 T-cell therapy was well tolerated and may have an acceptable DCR, this trial did not meet its primary efficacy endpoint.

Our findings showed that γδ T-cell therapy has potent benefit in cancer treatment.

Although the results cannot provide a definitive conclusion, the current suggested that ZAK cell AIT in combination with chemotherapy is safe, feasible and may be a promising treatment option for patients with incurable gastric cancer. The GPS value at baseline may be a potential biomarker for chemo-immunotherapy.

ZA suppressed M2-like TAMs induced TC cell proliferation, stemness and metastasis through inhibiting M2-like TAMs polarization and Wnt/β-catenin pathway, which sheds light on the mechanisms of TC and provides avenues for the development of clinical therapy to TC.

P3, N=6097, Active, not recruiting, Southwest Oncology Group | Trial completion date: May 2020 --> Jan 2021