Urokinase plasminogen activator receptor(uPAR) is implicated in tumor growth and metastasis due to its ability to activate latent growth factors, proteases, and different oncogenic signaling pathways upon binding to d...Urokinase plasminogen activator receptor(uPAR) is implicated in tumor growth and metastasis due to its ability to activate latent growth factors, proteases, and different oncogenic signaling pathways upon binding to different ligands. Elevated u PAR expression is correlated with the increased aggressiveness of cancer cells, which led to its credentialing as an attractive diagnostic and therapeutic target in advanced solid cancer. Here, we examine the antitumor effects of a humanized anti-u PAR antibody(huATN-658) alone and in combination with the approved bisphosphonate Zometa(Zoledronic acid) on skeletal lesion through a series of studies in vitro and in vivo. Treatment with huATN-658 or Zometa alone significantly decreased human MDA-MB-231 cell proliferation and invasion in vitro, effects which were more pronounced when huATN-658 was combined with Zometa. In vivo studies demonstrated that huATN-658 treatment significantly reduced MDA-MB-231 primary tumor growth compared with controls. In a model of breast tumor-induced bone disease, huATN-658 and Zometa were equally effective in reducing skeletal lesions. The skeletal lesions were significantly reduced in animals receiving the combination of huATN-658 + Zometa compared with monotherapy treatment. These effects were due to a significant decrease in osteoclastic activity and tumor cell proliferation in the combination treatment group. Transcriptome analysis revealed that combination treatment significantly changes the expression of genes from signaling pathways implicated in tumor progression and bone remodeling. Results from these studies provide a rationale for the continued development of huATN-658 as a monotherapy and in combination with currently approved agents such as Zometa in patients with metastatic breast cancer.展开更多
Background: The EDH occurs due to the accumulation of bleeding between the inner table of the skull and the outer layer of the dura mater. It is said to account for 1% - 3% of all head injured patients and 9% of those...Background: The EDH occurs due to the accumulation of bleeding between the inner table of the skull and the outer layer of the dura mater. It is said to account for 1% - 3% of all head injured patients and 9% of those who are comatose. The only life-saving treatment of choice is evacuation of EDH via craniotomy. Methods: This was a prospective observational study, where 40 patients were in follow-up for determining the outcomes of evacuation via craniotomy. Results: Majority of the patients were young and males. The main outcome of the evacuation was favorable (recovered), but certain unfavorable outcomes were also accounted like mortality. Conclusion: The pre-surgery clinical findings like consciousness of patient were an important indicator for EDH evacuation outcome. In most of the cases, the outcome was favorable with progressive recovery.展开更多
Background: A new method of immune-based therapies has been made and applied on multiple sclerosis patients in last decades. Some of these treatments have a high efficacy and reasonable side effects. In slowing diseas...Background: A new method of immune-based therapies has been made and applied on multiple sclerosis patients in last decades. Some of these treatments have a high efficacy and reasonable side effects. In slowing disease progression, present treatments have significant limitations, but often associated with significant adverse effects of immunosuppression, with having a bit low capability to counter the disability. Methods: This is a review meta-analysis of treatment of multiple sclerosis. Results: Thus a valuable aim for multiple sclerosis clinical research is to introduce more effective therapies. Conclusion: It is absolutely necessary to increase the individualized therapy planes development in respect to make better planes to disease-modifying treatments.展开更多
基金supported by grants from the Canadian Institutes for Health Research (PJT-156225) to SAR。
文摘Urokinase plasminogen activator receptor(uPAR) is implicated in tumor growth and metastasis due to its ability to activate latent growth factors, proteases, and different oncogenic signaling pathways upon binding to different ligands. Elevated u PAR expression is correlated with the increased aggressiveness of cancer cells, which led to its credentialing as an attractive diagnostic and therapeutic target in advanced solid cancer. Here, we examine the antitumor effects of a humanized anti-u PAR antibody(huATN-658) alone and in combination with the approved bisphosphonate Zometa(Zoledronic acid) on skeletal lesion through a series of studies in vitro and in vivo. Treatment with huATN-658 or Zometa alone significantly decreased human MDA-MB-231 cell proliferation and invasion in vitro, effects which were more pronounced when huATN-658 was combined with Zometa. In vivo studies demonstrated that huATN-658 treatment significantly reduced MDA-MB-231 primary tumor growth compared with controls. In a model of breast tumor-induced bone disease, huATN-658 and Zometa were equally effective in reducing skeletal lesions. The skeletal lesions were significantly reduced in animals receiving the combination of huATN-658 + Zometa compared with monotherapy treatment. These effects were due to a significant decrease in osteoclastic activity and tumor cell proliferation in the combination treatment group. Transcriptome analysis revealed that combination treatment significantly changes the expression of genes from signaling pathways implicated in tumor progression and bone remodeling. Results from these studies provide a rationale for the continued development of huATN-658 as a monotherapy and in combination with currently approved agents such as Zometa in patients with metastatic breast cancer.
文摘Background: The EDH occurs due to the accumulation of bleeding between the inner table of the skull and the outer layer of the dura mater. It is said to account for 1% - 3% of all head injured patients and 9% of those who are comatose. The only life-saving treatment of choice is evacuation of EDH via craniotomy. Methods: This was a prospective observational study, where 40 patients were in follow-up for determining the outcomes of evacuation via craniotomy. Results: Majority of the patients were young and males. The main outcome of the evacuation was favorable (recovered), but certain unfavorable outcomes were also accounted like mortality. Conclusion: The pre-surgery clinical findings like consciousness of patient were an important indicator for EDH evacuation outcome. In most of the cases, the outcome was favorable with progressive recovery.
文摘Background: A new method of immune-based therapies has been made and applied on multiple sclerosis patients in last decades. Some of these treatments have a high efficacy and reasonable side effects. In slowing disease progression, present treatments have significant limitations, but often associated with significant adverse effects of immunosuppression, with having a bit low capability to counter the disability. Methods: This is a review meta-analysis of treatment of multiple sclerosis. Results: Thus a valuable aim for multiple sclerosis clinical research is to introduce more effective therapies. Conclusion: It is absolutely necessary to increase the individualized therapy planes development in respect to make better planes to disease-modifying treatments.
