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| 1 | uPAR antibody(huATN-658) and Zometa reduce breast cancer growth and skeletal lesions显示文摘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. | Niaz Mahmood Ani Arakelian Haseeb Ahmed Khan Imrana Tanvir Andrew P.Mazar Shafaat A.Rabbani | 2020 | Bone Research2020，8，2： | 3 |
| 2 | Investigation into wall wrinkling in deep drawing process of conical cups显示文摘 | SHAFAAT M A ABBASI M KETABCHI M | 2011 | Journal of Materials Processing Technology2011，211，11： | 1 |
| 3 | Minimum time on-line joint trajectory generator based on low order spline method for industrial manipulators 显示文摘 | Shafaat A B Bertrand T | 1999 | Robotics and Autonomous Systems1999，29，4： | 1 |
| 4 | Methylation and inhibition of expression of uPA by the RAS oncogene: divergence of growth control and invasion in treast cancer cells显示文摘 | Pouya Pakneshan Moshe Szyf Shafaat A Rabbani | 2005 | Carcinogenesis2005，26，3： | 1 |
| 5 | Eficlive extraction of cephalosporin C from whole fermentation broth of Acremonium ehry:sogenum utilizing aqueous two phase systems显示文摘 | Wajid A Malik F Shafaat S et at | 2012 | A(riean Journal of Biotechnology2012，11，31： | 1 |
| 6 | Overexpression of urokinase in breast cancer cells results in increased tumor invasion,growth, metastasis显示文摘 | Rosic HX Shafaat AR | 1996 | Int J Cancer1996，67，2： | 1 |
| 7 | Comparative Study of Internal Batch Mixer such as Cam, Banbury and Roller: Numerical Simulation and Experimental Verification 显示文摘 | Shafaat A S Rabeh H E Othman A | 2011 | Chemical Engineering Science2011，66，12： | 1 |
| 8 | Methylation and inhibition of expression of uPA by the RAS oncogene : divergence of growth control and invasion in breast cancer cells 显示文摘 | Pouya Pakneshan Moshe Szyf Shafaat A Rabbani | 2005 | Carcinogenesis2005，26，3： | 1 |
| 9 | Chronic lithium treatment protects the rat kidney against ischemia/reperfusion injury: The role of nitric oxide and cyclooxygenase pathways显示文摘 | Saman Shafaat Talab Hamed Emami Azadeh Elmi Behtash Ghazi Nezami Solmaz Assa Armin Farajzadeh Deroee Ali Daneshmand Seyed Mohammad Tavangar Ahmad Reza Dehpour | 2010 | European Journal of Pharmacology2010，，1： | 1 |
| 10 | Effect of different yield criteria on prediction of wrinkling initiation of intersti- tial-free galvanized steel sheet 显示文摘 | Shafaat M A Abbasi M Ketabchi M | 2011 | Materials & Design2011，32，6： | 1 |
| 11 | Cholestasis induced nephrotoxicity: The role of endogenous opioids显示文摘 | Armin Farajzadeh Deroee Behtash Ghazi Nezami Shahram Ejtemaei Mehr Rohollah Hosseini Amirali Hassanzadeh Salmasi Saman Shafaat Talab Issa Jahanzad Ahmad Reza Dehpour | 2010 | Life Sciences2010，，13： | 1 |
| 12 | Chronic Upregulation of the Endogenous Opioid System Impairs the Skin Flap Survival in Rats显示文摘 | Behtash Ghazi Nezami Saman Shafaat Talab Hamed Emami Solmaz Assa Mohammad Reza Rasouli Shahrzad Asadi Seyed Mohammad Tavangar Ahmad Reza Dehpour | 2009 | Annals of Plastic Surgery2009，，5： | 1 |
| 13 | Comparative Study of Internal Batch Mixer Such as Cam, Banbury and Roller: Numerical Simulation and Experimental Verification显示文摘 | Shafaat A S Rabeh H E Othraan A | 2011 | Chemical Engineering Science2011，66，12： | 1 |
| 14 | Methylation and inhibition of expression of uPA by the RAS oncogene:divergence of growth control and invasion in breast cancer cells显示文摘 | Pouya Pakneshan Moshe Szyf Shafaat A Rabbani | 2005 | Carcinogenesis2005，26，3： | 1 |
| 15 | Comparative Study of Internal Batch Mixer Such as Cam, Banbury and Roller : Numerical Simulation and Experimental Verification显示文摘 | Shafaat A S Rabeh H | 2011 | Chemical Engineering Science2011，66，12： | 1 |
| 16 | Investigation into wall wrinkling in deep drawing process of conical cups 显示文摘 | Mohammad Amin Shafaat Mahmoud Abbasi Mostafa Ketabchi | 2011 | Joumal of Materials Processing Technology2011，211，11： | 1 |
| 17 | An enhanced chemopreventive effect of methyl donor S-adenosylmethionine in combination with 25-hydroxyvitamin D in blocking mammary tumor growth and metastasis显示文摘Therapeutic targeting of metastatic breast cancer still remains a challenge as the tumor cells are highly heterogenous and exploit multiple pathways for their growth and metastatic spread that cannot always be targeted by a single-agent monotherapy regimen.Therefore,a rational approach through simultaneous targeting of several pathways may provide a better anti-cancer therapeutic effect We tested this hypothesis using a combination of two nutraceutical agents S-adenosylmethionine(SAM)and Vitamin D(Vit.D)prohormone[25-hydroxyvitamin D;/25(OH)D,]that are individually known to exert distinct changes in the expression of genes involved in tumor growth and metastasis.Our results show that both SAM and 25(OH)D monotherapy significantly reduced proliferation and clonogenic survival of a panel of breast cancer cell lines in vitro and inhibited tumor growth,lung metastasis,and breast tumor cell colonization to the skeleton in vivo.However,these effects were significantly more pronounced in the combination setting.RNA-Sequencing revealed that the transcriptomic footprint on key cancer-related signaling pathways is broader in the combination setting than any of the monotherapies.Furthermore,comparison of the differentially expressed genes from our transcriptome analyses with publicly available cancer-related dataset demonstrated that the combination treatment upregulates genes from immune-related pathways that are otherwise downregulated in bone metastasis in vivo.Since SAM and Vit.D are both approved nutraceuticals with known safety profiles,this combination treatment may serve as a novel strategy to reduce breast cancer-associated morbidity and mortality。 | Niaz Mahmood Ani Arakelian William J.Muller Moshe Szyf Shafaat A.Rabbani | 2020 | Bone Research2020，8，3： | 0 |
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