Reference(s)
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Category: Musculoskeletal sarcomas


Cancer Type: Osteosarcoma

HGF/SF expression

Reference Number: 141
Fukuda, T. et al. Coexpression of HGF and c-Met/HGF receptor in human bone and soft tissue tumors. Pathol Int 48, 757-62 (1998).
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Reference Number: 820
Chattopadhyay N, MacLeod RJ, Tfelt-Hansen J, Brown EM. 1alpha,25(OH)2-vitamin D3 inhibits HGF synthesis and secretion from MG-63 human osteosarcoma cells. Am J Physiol Endocrinol Metab. 284, E219-27 (2003)
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Reference Number: 821
Fieten H, Spee B, Ijzer J, Kik MJ, Penning LC, Kirpensteijn J. Expression of hepatocyte growth factor and the proto-oncogenic receptor c-Met in canine osteosarcoma. Vet Pathol. 46, 869-77 (2009)
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Reference Number: 990
Tsubaki M, Yamazoe Y, Yanae M, Satou T, Itoh T, Kaneko J, Kidera Y, Moriyama K, Nishida S. Blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathways by statins reduces the expression of bFGF, HGF, and TGF-ß as angiogenic factors in mouse osteosarcoma. Cytokine. 54, 100-7 (2011)
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Reference Number: 1128
Zhang L, Wang Y, Wang L, Cao T, Hyuga S, Sato T, Wu Y, Yamagata S, Yamagata T. Ganglioside GD1a negatively regulates hepatocyte growth factor expression through caveolin-1 at the transcriptional level in murine osteosarcoma cells. Biochim Biophys Acta. 1810, 759-68 (2011)
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Reference Number: 1805
Husmann K, Ducommun P, Sabile AA, Pedersen EM, Born W, Fuchs B. Signal transduction and downregulation of C-MET in HGF stimulated low and highly metastatic human osteosarcoma cells. Biochem Biophys Res Commun. 464, 1222-7 (2015)
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Met expression

Reference Number: 138
Rong, S. et al. Met expression and sarcoma tumorigenicity. Cancer Res 53, 5355-60 (1993).
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Reference Number: 141
Fukuda, T. et al. Coexpression of HGF and c-Met/HGF receptor in human bone and soft tissue tumors. Pathol Int 48, 757-62 (1998).
PubMed link      E-mail link

Reference Number: 142
Arihiro, K. & Inai, K. Expression of CD31, Met/hepatocyte growth factor receptor and bone morphogenetic protein in bone metastasis of osteosarcoma. Pathol Int 51, 100-6 (2001).
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Reference Number: 143
Ferracini, R. et al. The Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit. Oncogene 10, 739-49 (1995).
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Reference Number: 144
Oda, Y., Naka, T., Takeshita, M., Iwamoto, Y. & Tsuneyoshi, M. Comparison of histological changes and changes in nm23 and c-MET expression between primary and metastatic sites in osteosarcoma: a clinicopathologic and immunohistochemical study. Hum Pathol 31, 709-16 (2000).
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Reference Number: 411
Patane S, Avnet S, Coltella N, Costa B, Sponza S, Olivero M, Vigna E, Naldini L, Baldini N, Ferracini R, Corso S, Giordano S, Comoglio PM, Di Renzo MF. MET overexpression turns human primary osteoblasts into osteosarcomas. Cancer Res. 66, 4750-7 (2006)
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Reference Number: 819
Coltella N, Manara MC, Cerisano V, Trusolino L, Di Renzo MF, Scotlandi K, Ferracini R. Role of the MET/HGF receptor in proliferation and invasive behavior of osteosarcoma. FASEB J. 17, 1162-4 (2003)
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Reference Number: 821
Fieten H, Spee B, Ijzer J, Kik MJ, Penning LC, Kirpensteijn J. Expression of hepatocyte growth factor and the proto-oncogenic receptor c-Met in canine osteosarcoma. Vet Pathol. 46, 869-77 (2009)
PubMed link      E-mail link

Reference Number: 1059
Hassan SE, Bekarev M, Kim MY, Lin J, Piperdi S, Gorlick R, Geller DS. Cell surface receptor expression patterns in osteosarcoma. Cancer. 118, 740-9 (2012)
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Reference Number: 1127
Sampson ER, Martin BA, Morris AE, Xie C, Schwarz EM, O'Keefe RJ, Rosier RN. The orally bioavailable met inhibitor PF-2341066 inhibits osteosarcoma growth and osteolysis/matrix production in a xenograft model. J Bone Miner Res. 26, 1283-94 (2011)
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Reference Number: 1198
Dani N, Olivero M, Mareschi K, van Duist MM, Miretti S, Cuvertino S, Patané S, Calogero R, Ferracini R, Scotlandi K, Fagioli F, Di Renzo MF. The MET oncogene transforms human primary bone-derived cells into osteosarcomas by targeting committed osteo-progenitors. J Bone Miner Res. 27, 1322-34 (2012)
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Reference Number: 1202
Yan K, Gao J, Yang T, Ma Q, Qiu X, Fan Q, Ma B. MicroRNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo. PLoS One. 7, e33778 (2012)
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Reference Number: 1411
Novello C1, Pazzaglia L, Cingolani C, Conti A, Quattrini I, Manara MC, Tognon M, Picci P, Benassi MS. miRNA expression profile in human osteosarcoma: role of miR-1 and miR-133b in proliferation and cell cycle control. Int J Oncol. 42, 667-75 (2013)
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Reference Number: 1663
Niu G, Li B, Sun J, Sun L. miR-454 is down-regulated in osteosarcomas and suppresses cell proliferation and invasion by directly targeting c-Met. Cell Prolif. 48, 348-55 (2015)
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Reference Number: 1767
Jiang C, Chen H, Shao L, Wang Q MicroRNA-1 functions as a potential tumor suppressor in osteosarcoma by targeting Med1 and Med31. Oncol Rep. 32, 1249-56 (2014)
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Reference Number: 1805
Husmann K, Ducommun P, Sabile AA, Pedersen EM, Born W, Fuchs B. Signal transduction and downregulation of C-MET in HGF stimulated low and highly metastatic human osteosarcoma cells. Biochem Biophys Res Commun. 464, 1222-7 (2015)
PubMed link      E-mail link

Poor Prognosis

Mutation of Met

Reference Number: 411
Patane S, Avnet S, Coltella N, Costa B, Sponza S, Olivero M, Vigna E, Naldini L, Baldini N, Ferracini R, Corso S, Giordano S, Comoglio PM, Di Renzo MF. MET overexpression turns human primary osteoblasts into osteosarcomas. Cancer Res. 66, 4750-7 (2006)
PubMed link      E-mail link

In vitro studies

Reference Number: 143
Ferracini, R. et al. The Met/HGF receptor is over-expressed in human osteosarcomas and is activated by either a paracrine or an autocrine circuit. Oncogene 10, 739-49 (1995).
PubMed link      E-mail link

Reference Number: 265
MacEwen EG, Kutzke J, Carew J, Pastor J, Schmidt JA, Tsan R, Thamm DH, Radinsky R. c-Met tyrosine kinase receptor expression and function in human and canine osteosarcoma cells. Clin Exp Metastasis 20:421-30 (2003).
PubMed link      E-mail link

Reference Number: 411
Patane S, Avnet S, Coltella N, Costa B, Sponza S, Olivero M, Vigna E, Naldini L, Baldini N, Ferracini R, Corso S, Giordano S, Comoglio PM, Di Renzo MF. MET overexpression turns human primary osteoblasts into osteosarcomas. Cancer Res. 66, 4750-7 (2006)
PubMed link      E-mail link

Reference Number: 819
Coltella N, Manara MC, Cerisano V, Trusolino L, Di Renzo MF, Scotlandi K, Ferracini R. Role of the MET/HGF receptor in proliferation and invasive behavior of osteosarcoma. FASEB J. 17, 1162-4 (2003)
PubMed link      E-mail link

Reference Number: 823
Cantiani L, Manara MC, Zucchini C, De Sanctis P, Zuntini M, Valvassori L, Serra M, Olivero M, Di Renzo MF, Colombo MP, Picci P, Scotlandi K. Caveolin-1 reduces osteosarcoma metastases by inhibiting c-Src activity and met signaling. Cancer Res. 67, 7675-85 (2007)
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Reference Number: 1502
McCleese JK, Bear MD, Kulp SK, Mazcko C, Khanna C, London CA. Met interacts with EGFR and Ron in canine osteosarcoma. Vet Comp Oncol. 11, 124-39 (2013)
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Animal models

Reference Number: 145
Ferracini, R. et al. MET oncogene aberrant expression in canine osteosarcoma. J Orthop Res 18, 253-6. (2000).
PubMed link      E-mail link

Reference Number: 821
Fieten H, Spee B, Ijzer J, Kik MJ, Penning LC, Kirpensteijn J. Expression of hepatocyte growth factor and the proto-oncogenic receptor c-Met in canine osteosarcoma. Vet Pathol. 46, 869-77 (2009)
PubMed link      E-mail link

Reference Number: 822
De Maria R, Miretti S, Iussich S, Olivero M, Morello E, Bertotti A, Christensen JG, Biolatti B, Levine RA, Buracco P, Di Renzo MF.
met oncogene activation qualifies spontaneous canine osteosarcoma as a suitable pre-clinical model of human osteosarcoma. J Pathol. 218, 399-408 (2009)

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Reference Number: 990
Tsubaki M, Yamazoe Y, Yanae M, Satou T, Itoh T, Kaneko J, Kidera Y, Moriyama K, Nishida S. Blockade of the Ras/MEK/ERK and Ras/PI3K/Akt pathways by statins reduces the expression of bFGF, HGF, and TGF-ß as angiogenic factors in mouse osteosarcoma. Cytokine. 54, 100-7 (2011)
PubMed link      E-mail link

Therapeutic Development

Reference Number: 411
Patane S, Avnet S, Coltella N, Costa B, Sponza S, Olivero M, Vigna E, Naldini L, Baldini N, Ferracini R, Corso S, Giordano S, Comoglio PM, Di Renzo MF. MET overexpression turns human primary osteoblasts into osteosarcomas. Cancer Res. 66, 4750-7 (2006)
PubMed link      E-mail link

Reference Number: 1112
McQueen P, Ghaffar S, Guo Y, Rubin EM, Zi X, Hoang BH. The Wnt signaling pathway: implications for therapy in osteosarcoma. Expert Rev Anticancer Ther. 11, 1223-32 (2011)
PubMed link      E-mail link

Reference Number: 1127
Sampson ER, Martin BA, Morris AE, Xie C, Schwarz EM, O'Keefe RJ, Rosier RN. The orally bioavailable met inhibitor PF-2341066 inhibits osteosarcoma growth and osteolysis/matrix production in a xenograft model. J Bone Miner Res. 26, 1283-94 (2011)
PubMed link      E-mail link

Reference Number: 1231
Wang K, Zhuang Y, Liu C, Li Y. Inhibition of c-Met activation sensitizes osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling. Arch Biochem Biophys. 526, 38-43 (2012)
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Reviews

Cancer Type: Synovial Sarcoma

HGF/SF expression

Reference Number: 146
Kuhnen, C., Tolnay, E., Steinau, H. U., Voss, B. & Muller, K. M. Expression of c-Met receptor and hepatocyte growth factor/scatter factor in synovial sarcoma and epithelioid sarcoma. Virchows Arch 432, 337-42 (1998).
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Reference Number: 147
Motoi, T. et al. Coexpression of hepatocyte growth factor and c-Met proto-oncogene product in synovial sarcoma. Pathol Int 48, 769-75 (1998).
PubMed link      E-mail link

Reference Number: 148
Oda, Y. et al. Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma. Hum Pathol 31, 185-92 (2000).
PubMed link      E-mail link

Met expression

Reference Number: 146
Kuhnen, C., Tolnay, E., Steinau, H. U., Voss, B. & Muller, K. M. Expression of c-Met receptor and hepatocyte growth factor/scatter factor in synovial sarcoma and epithelioid sarcoma. Virchows Arch 432, 337-42 (1998).
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Reference Number: 147
Motoi, T. et al. Coexpression of hepatocyte growth factor and c-Met proto-oncogene product in synovial sarcoma. Pathol Int 48, 769-75 (1998).
PubMed link      E-mail link

Reference Number: 148
Oda, Y. et al. Expression of hepatocyte growth factor (HGF)/scatter factor and its receptor c-MET correlates with poor prognosis in synovial sarcoma. Hum Pathol 31, 185-92 (2000).
PubMed link      E-mail link

Reference Number: 1517
Yasui H1, Naka N2, Imura Y3, Outani H3, Kaneko K3, Hamada K3, Sasagawa S4, Araki N5, Ueda T6, Itoh K4, Myoui A3, Yoshikawa H3. Tailored therapeutic strategies for synovial sarcoma: receptor tyrosine kinase pathway analyses predict sensitivity to the mTOR inhibitor RAD001. Cancer Lett. 347, 114-22 (2014)
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Poor Prognosis

Mutation of Met

In vitro studies

Reference Number: 498
Watanabe T, Tsuda M, Makino Y, Ichihara S, Sawa H, Minami A, Mochizuki N, Nagashima K, Tanaka S. Adaptor molecule Crk is required for sustained phosphorylation of Grb2-associated binder 1 and hepatocyte growth factor-induced cell motility of human synovial sarcoma cell lines. Mol Cancer Res. 4, 499-510 (2006)
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Animal models

Therapeutic Development

Reference Number: 1517
Yasui H1, Naka N2, Imura Y3, Outani H3, Kaneko K3, Hamada K3, Sasagawa S4, Araki N5, Ueda T6, Itoh K4, Myoui A3, Yoshikawa H3. Tailored therapeutic strategies for synovial sarcoma: receptor tyrosine kinase pathway analyses predict sensitivity to the mTOR inhibitor RAD001. Cancer Lett. 347, 114-22 (2014)
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Reviews

Cancer Type: Rhabdomyosarcoma

HGF/SF expression

Reference Number: 510
Rees H, Williamson D, Papanastasiou A, Jina N, Nabarro S, Shipley J, Anderson J. The MET receptor tyrosine kinase contributes to invasive tumour growth in rhabdomyosarcomas. Growth Factors. 24, 197-208 (2006)
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Reference Number: 531
Williamson D, Selfe J, Gordon T, Lu YJ, Pritchard-Jones K, Murai K, Jones P, Workman P, Shipley J. Role for amplification and expression of glypican-5 in rhabdomyosarcoma. Cancer Res. 67, 57-65 (2007)
PubMed link      E-mail link

Met expression

Reference Number: 149
Ginsberg, J. P., Davis, R. J., Bennicelli, J. L., Nauta, L. E. & Barr, F. G. Up-regulation of MET but not neural cell adhesion molecule expression by the PAX3-FKHR fusion protein in alveolar rhabdomyosarcoma. Cancer Res 58, 3542-6 (1998).
PubMed link      E-mail link

Reference Number: 510
Rees H, Williamson D, Papanastasiou A, Jina N, Nabarro S, Shipley J, Anderson J. The MET receptor tyrosine kinase contributes to invasive tumour growth in rhabdomyosarcomas. Growth Factors. 24, 197-208 (2006)
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Reference Number: 583
Lesko E, Gozdzik J, Kijowski J, Jenner B, Wiecha O, Majka M. HSP90 antagonist, geldanamycin, inhibits proliferation, induces apoptosis and blocks migration of rhabdomyosarcoma cells in vitro and seeding into bone marrow in vivo. Anticancer Drugs. 18, 1173-81 (2007)
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Reference Number: 653
Diomedi-Camassei F, McDowell HP, De Ioris MA, Uccini S, Altavista P, Raschellà G, Vitali R, Mannarino O, De Sio L, Cozzi DA, Donfrancesco A, Inserra A, Callea F, Dominici C. Clinical significance of CXC chemokine receptor-4 and c-Met in childhood rhabdomyosarcoma. Clin Cancer Res. 14, 4119-27, (2008)

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Reference Number: 818
Yan D, Dong Xda E, Chen X, Wang L, Lu C, Wang J, Qu J, Tu L. MicroRNA-1/206 targets c-Met and inhibits rhabdomyosarcoma development. J Biol Chem. 284, 29596-604 (2009)
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Reference Number: 1126
Hou J, Dong J, Sun L, Geng L, Wang J, Zheng J, Li Y, Bridge J, Hinrichs SH, Ding SJ. Inhibition of phosphorylated c-Met in rhabdomyosarcoma cell lines by a small molecule inhibitor SU11274. J Transl Med. 9, 64 (2011)
PubMed link      E-mail link

Reference Number: 1324
Miekus K, Lukasiewicz E, Jarocha D, Sekula M, Drabik G, Majka M. The decreased metastatic potential of rhabdomyosarcoma cells obtained through MET receptor downregulation and the induction of differentiation. Cell Death Dis. 4: e459 (2013)
PubMed link      E-mail link

Poor Prognosis

Reference Number: 572
Chen Y, Takita J, Mizuguchi M, Tanaka K, Ida K, Koh K, Igarashi T, Hanada R, Tanaka Y, Park MJ, Hayashi Y. Mutation and expression analyses of the MET and CDKN2A genes in rhabdomyosarcoma with emphasis on MET overexpression. Genes Chromosomes Cancer. 46, 348-58 (2007)
PubMed link      E-mail link

Mutation of Met

In vitro studies

Reference Number: 149
Ginsberg, J. P., Davis, R. J., Bennicelli, J. L., Nauta, L. E. & Barr, F. G. Up-regulation of MET but not neural cell adhesion molecule expression by the PAX3-FKHR fusion protein in alveolar rhabdomyosarcoma. Cancer Res 58, 3542-6 (1998).
PubMed link      E-mail link

Reference Number: 150
Epstein, J. A., Shapiro, D. N., Cheng, J., Lam, P. Y. & Maas, R. L. Pax3 modulates expression of the c-Met receptor during limb muscle development. Proc Natl Acad Sci U S A 93, 4213-8 (1996).
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Reference Number: 263
Jankowski K, Kucia M, Wysoczynski M, Reca R, Zhao D, Trzyna E, Trent J, Peiper S, Zembala M, Ratajczak J, Houghton P, Janowska-Wieczorek A, Ratajczak MZ. Both hepatocyte growth factor (HGF) and stromal-derived factor-1 regulate the metastatic behavior of human rhabdomyosarcoma cells, but only HGF enhances their resistance to radiochemotherapy. Cancer Res 63:7926-35 (2003).
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Reference Number: 410
Taulli R, Scuoppo C, Bersani F, Accornero P, Forni PE, Miretti S, Grinza A, Allegra P, Schmitt-Ney M, Crepaldi T, Ponzetto C. Validation of met as a therapeutic target in alveolar and embryonal rhabdomyosarcoma. Cancer Res. 66, 4742-9 (2006)
PubMed link      E-mail link

Reference Number: 531
Williamson D, Selfe J, Gordon T, Lu YJ, Pritchard-Jones K, Murai K, Jones P, Workman P, Shipley J. Role for amplification and expression of glypican-5 in rhabdomyosarcoma. Cancer Res. 67, 57-65 (2007)
PubMed link      E-mail link

Reference Number: 572
Chen Y, Takita J, Mizuguchi M, Tanaka K, Ida K, Koh K, Igarashi T, Hanada R, Tanaka Y, Park MJ, Hayashi Y. Mutation and expression analyses of the MET and CDKN2A genes in rhabdomyosarcoma with emphasis on MET overexpression. Genes Chromosomes Cancer. 46, 348-58 (2007)
PubMed link      E-mail link

Reference Number: 583
Lesko E, Gozdzik J, Kijowski J, Jenner B, Wiecha O, Majka M. HSP90 antagonist, geldanamycin, inhibits proliferation, induces apoptosis and blocks migration of rhabdomyosarcoma cells in vitro and seeding into bone marrow in vivo. Anticancer Drugs. 18, 1173-81 (2007)
PubMed link      E-mail link

Reference Number: 1324
Miekus K, Lukasiewicz E, Jarocha D, Sekula M, Drabik G, Majka M. The decreased metastatic potential of rhabdomyosarcoma cells obtained through MET receptor downregulation and the induction of differentiation. Cell Death Dis. 4: e459 (2013)
PubMed link      E-mail link

Animal models

Reference Number: 28
Takayama, H. et al. Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor. Proc Natl Acad Sci U S A 94, 701-6 (1997).
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Reference Number: 151
Sharp, R. et al. Synergism between INK4a/ARF inactivation and aberrant HGF/SF signaling in rhabdomyosarcomagenesis. Nat Med 8, 1276-80 (2002).
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Reference Number: 817
Lukasiewicz E, Miekus K, Kijowski J, Drabik G, Wilusz M, Bobis-Wozowicz S, Majka M. Inhibition of rhabdomyosarcoma's metastatic behavior through downregulation of MET receptor signaling. Folia Histochem Cytobiol. 47, 485-9 (2009)
PubMed link      E-mail link

Therapeutic Development

Reference Number: 583
Lesko E, Gozdzik J, Kijowski J, Jenner B, Wiecha O, Majka M. HSP90 antagonist, geldanamycin, inhibits proliferation, induces apoptosis and blocks migration of rhabdomyosarcoma cells in vitro and seeding into bone marrow in vivo. Anticancer Drugs. 18, 1173-81 (2007)
PubMed link      E-mail link

Reference Number: 1126
Hou J, Dong J, Sun L, Geng L, Wang J, Zheng J, Li Y, Bridge J, Hinrichs SH, Ding SJ. Inhibition of phosphorylated c-Met in rhabdomyosarcoma cell lines by a small molecule inhibitor SU11274. J Transl Med. 9, 64 (2011)
PubMed link      E-mail link

Reference Number: 1245
Chadalapaka G, Jutooru I, Sreevalsan S, Pathi S, Kim K, Chen C, Crose L, Linardic C, Safe S. Inhibition of rhabdomyosarcoma cell and tumor growth by targeting specificity protein (Sp) transcription factors. Int J Cancer. 132, 795-806 (2013)
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Reference Number: 1373
Houghton PJ, Kurmasheva RT, Kolb EA, Wu J, Gorlick R, Maris JM, Smith MA. Initial testing (Stage 1) of TAK-701, a humanized hepatocyte growth factor binding antibody, by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 61, 380-2 (2014)
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Reference Number: 1822
Ferguson M, Hingorani P, Gupta AA. Emerging molecular-targeted therapies in early-phase clinical trials and preclinical models. Am Soc Clin Oncol Educ Book. 420-4 (2013)
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Reviews