Search

The effect of rolling reduction and annealing process on the microstructure and corrosion behavior of Mg−9Li−1Zn (LZ91) alloy was investigated. The test alloy sheets were cold rolled with the reduction of 50% and 75%, respectively, and then were annealed at 200 °C for 1 h. The microstructure of test alloys was observed by OM and SEM while the phase composition was determined by XRD. The corrosion property was evaluated by electrochemical measurements and immersion tests. The results show that LZ91 alloy sheet consists of α-Mg, β-Li and precipitated Mg−Li−Zn compounds (MgLi2Zn and MgLiZn phases). Dynamic recrystallization grains appear in β-Li phase during annealing process, leading to grain refinement. The results indicate that the increasing rolling reduction and performing the annealing process can enhance the corrosion resistance of LZ91 alloy. The 75% cold-rolled and annealed LZ91 alloy shows the best corrosion resistance.

The as-cast Mg-6.5Li-xY-yZn alloys (Mg-6.5Li-0.8Y, Mg-6.5Li-0.8Y-0.3Zn and Mg-6.5Li-1.0Y-1.0Zn) were extruded at 553 K with an extrusion ratio of 25:1 and a constant extrusion speed of 1.6 mm/s. The microstructure and corrosion behavior of as-extruded Mg-6.5Li-xY-yZn alloys were studied by microstructure observation, weight loss test, hydrogen evolution test and electrochemical test in present work. The microstructure shows that the Mg-6.5Li-0.8Y alloy contains α-Mg, β-Li and Mg2Y phase, the Mg-6.5Li-0.8Y-0.3Zn alloy is composed of α-Mg, β-Li and X phase (Mg12ZnY, LPSO phase) and the Mg-6.5Li-1.0Y-1.0Zn alloy consists of α-Mg, β-Li and W phase (Mg3Zn3Y2). The corrosion results indicate that the combining addition of Y and Zn can improve the corrosion resistance of Mg-6.5Li alloys and Mg-6.5Li-0.8Y-0.3Zn alloy with LPSO phase possesses the best corrosion resistance. The surface microstructure of test alloys after immersed in 3.5 wt% NaCl solution for 48 h, showing that the Mg-6.5Li-0.8Y alloy has the most corrosion pits while the Mg-6.5Li-0.8Y-0.3Zn alloy has the least corrosion pits due to the minimal micro-galvanic formed on its surface.

Bisphosphonates (BPs), bone targeted drugs that disrupt osteoclast function, are routinely used to treat complications of bone metastasis. Studies in preclinical models of cancer have shown that BPs reduce skeletal tumor burden and increase survival. Similarly, we observed in the present study that administration of the Nitrogen-containing BP (N-BP), zoledronic acid (ZA) to osteolytic tumor-bearing Tax+ mice beginning at 6 months of age led to resolution of radiographic skeletal lesions. N-BPs inhibit farnesyl diphosphate (FPP) synthase, thereby inhibiting protein prenylation and causing cellular toxicity. We found that ZA decreased Tax+ tumor and B16 melanoma viability and caused the accumulation of unprenylated Rap1a proteins in vitro. However, it is presently unclear whether N-BPs exert anti-tumor effects in bone independent of inhibition of osteoclast (OC) function in vivo. Therefore, we evaluated the impact of treatment with ZA on B16 melanoma bone tumor burden in irradiated mice transplanted with splenic cells from src(-/-) mice, which have non-functioning OCs. OC-defective mice treated with ZA demonstrated a significant 88% decrease in tumor growth in bone compared to vehicle-treated OC-defective mice. These data support an osteoclast-independent role for N-BP therapy in bone metastasis.

Interferon-gamma (IFN-gamma) has been shown to enhance anti-tumor immunity and inhibit the formation of bone-resorbing osteoclasts. We evaluated the role of IFN-gamma in bone metastases, tumor-associated bone destruction, and hypercalcemia in human T cell lymphotrophic virus type 1-Tax transgenic mice. Compared with Tax(+)IFN-gamma(+/+) mice, Tax(+)IFN-gamma(-/-) mice developed increased osteolytic bone lesions and soft tissue tumors, as well as increased osteoclast formation and activity. In vivo administration of IFN-gamma to tumor-bearing Tax(+)IFN-gamma(-/-) mice prevented new tumor development and resulted in decreased bromodeoxyuridine uptake by established tumors. In vitro, IFN-gamma directly decreased the viability of Tax(+) tumor cells through inhibition of proliferation, suppression of ERK phosphorylation, and induction of apoptosis and caspase 3 cleavage. IFN-gamma also inhibited macrophage colonystimulating factor-mediated proliferation and survival of osteoclast progenitors in vitro. Administration of IFN-gamma to C57BL/6 mice decreased Tax(+) tumor growth and prevented tumor-associated bone loss and hypercalcemia. In contrast, IFN-gamma treatment failed to protect IFN-gammaR1(-/-) mice from Tax(+) tumor-induced skeletal complications, despite decreasing tumor growth. These data demonstrate that IFN-gamma suppressed tumor-induced bone loss and hypercalcemia in Tax(+) mice by inhibiting both Tax(+) tumor cell growth and host-induced osteolysis. These data suggest a protective role for IFN-gamma in patients with bone metastases and hypercalcemia of malignancy.