Bone is one of the most preferential metastatic target sites of breast cancer. Bone possesses unique biological microenvironments in which various growth factors are stored and continuously released through osteoclast...Bone is one of the most preferential metastatic target sites of breast cancer. Bone possesses unique biological microenvironments in which various growth factors are stored and continuously released through osteoclastic bone resorption, providing fertile soil for circulating breast cancer cells. Bone-disseminated breast cancer cells in turn produce osteotropic cytokines which modulate bone environments. Under the influences of breast cancer-produced cytokines, osteoblasts express elevated levels of Ligand for receptor activator of nuclear factor-κB(RANKL) and stimulate osteoclastogenesis via binding to the receptor receptor activator of nuclear factor-κB(RANK) and activating its downstream signaling pathways in hematopoietic osteoclast precursors, which causes further osteoclastic bone destruction. Establishment of crosstalk with bone microenvironments(so called vicious cycle) is an essential event for metastatic breast cancer cells to develop bone metastasis. RANKL and RANK play a central role in this crosstalk. Moreover, recent studies have demonstrated that RANKL and RANK are involved in tumorigenesis and distant metastasis independent of bone microenvironments. Pharmacological disruption of the RANKL/RANK interplay should be an effective therapeutic intervention for primary breast tumors and bone and non-bone metastasis. In this context, denosumab, which is neutralizing monoclonal antibody against RANKL, is a mechanismbased drug for the treatment of bone metastases and would be beneficial for breast cancer patients with bone metastases and potentially visceral organ metastases.展开更多
The development is described of an electromechanical bimorph actuator composed of ionic liquid gel sandwiched by electrochemically treated millimeter-long single-walled carbon nanotubes(SG-SWNT).Electrochemical doping...The development is described of an electromechanical bimorph actuator composed of ionic liquid gel sandwiched by electrochemically treated millimeter-long single-walled carbon nanotubes(SG-SWNT).Electrochemical doping of the SG-SWNT and electrochemical polymerization of polypyrrole on the surface of the SG-SWNT improved the performance of a previously reported actuator using non-treated SG-SWNTs.The conductivity of the SG-SWNT sheets treated at the anodic potential(doped)was found to be three times larger than that of the original film.The generated strain of the actuator prepared from the doped SG-SWNT sheets was increased compared to that prepared from non-doped sample.Moreover,the generated strain of the actuator from the doped SG-SWNT sheets swelled with ionic liquid(IL)was increased to twice that without ILs.The electropolymerization of pyrrole on the surface of the SG-SWNT sheet was carried out.The conductivity of the SG-SWNT was seven times larger after the electropolymerization.The generated strain of the SG-SWNT actuator prepared from the SG-SWNT sheets with electropolymerization was twice as large as that without the electropolymerization at low frequency.At higher frequency,both actuators provide almost the same performance.Both actuators exhibit mechanical resonance at about 100 Hz.展开更多
文摘Bone is one of the most preferential metastatic target sites of breast cancer. Bone possesses unique biological microenvironments in which various growth factors are stored and continuously released through osteoclastic bone resorption, providing fertile soil for circulating breast cancer cells. Bone-disseminated breast cancer cells in turn produce osteotropic cytokines which modulate bone environments. Under the influences of breast cancer-produced cytokines, osteoblasts express elevated levels of Ligand for receptor activator of nuclear factor-κB(RANKL) and stimulate osteoclastogenesis via binding to the receptor receptor activator of nuclear factor-κB(RANK) and activating its downstream signaling pathways in hematopoietic osteoclast precursors, which causes further osteoclastic bone destruction. Establishment of crosstalk with bone microenvironments(so called vicious cycle) is an essential event for metastatic breast cancer cells to develop bone metastasis. RANKL and RANK play a central role in this crosstalk. Moreover, recent studies have demonstrated that RANKL and RANK are involved in tumorigenesis and distant metastasis independent of bone microenvironments. Pharmacological disruption of the RANKL/RANK interplay should be an effective therapeutic intervention for primary breast tumors and bone and non-bone metastasis. In this context, denosumab, which is neutralizing monoclonal antibody against RANKL, is a mechanismbased drug for the treatment of bone metastases and would be beneficial for breast cancer patients with bone metastases and potentially visceral organ metastases.
文摘The development is described of an electromechanical bimorph actuator composed of ionic liquid gel sandwiched by electrochemically treated millimeter-long single-walled carbon nanotubes(SG-SWNT).Electrochemical doping of the SG-SWNT and electrochemical polymerization of polypyrrole on the surface of the SG-SWNT improved the performance of a previously reported actuator using non-treated SG-SWNTs.The conductivity of the SG-SWNT sheets treated at the anodic potential(doped)was found to be three times larger than that of the original film.The generated strain of the actuator prepared from the doped SG-SWNT sheets was increased compared to that prepared from non-doped sample.Moreover,the generated strain of the actuator from the doped SG-SWNT sheets swelled with ionic liquid(IL)was increased to twice that without ILs.The electropolymerization of pyrrole on the surface of the SG-SWNT sheet was carried out.The conductivity of the SG-SWNT was seven times larger after the electropolymerization.The generated strain of the SG-SWNT actuator prepared from the SG-SWNT sheets with electropolymerization was twice as large as that without the electropolymerization at low frequency.At higher frequency,both actuators provide almost the same performance.Both actuators exhibit mechanical resonance at about 100 Hz.
