Targeting protein kinase C in sarcoma

Biochimica et Biophysica Acta - Reviews on Cancer

Volumn 1846, Issue 2, 2014, Pages 547-559

  Martin Liberal, J ^a   Cameron, A J ^c   Claus, J ^d   Judson, I R ^a   Parker, P J ^d,e   Linch, M ^b  

^a ROYAL MARSDEN HOSPITAL   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^d IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

^e KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Kinases; Protein kinase C; Sarcoma; Therapeutics

Indexed keywords

ANTINEOPLASTIC AGENT; APRINOCARSEN; AUROTHIOMALATE; BYROSTATIN 1; CARBOPLATIN; CRT 0066854; DELCASERTIB; ENZASTAURIN; IMATINIB; MIDOSTAURIN; PACLITAXEL; PROTEIN KINASE C; PROTEIN KINASE C BETA; PROTEIN KINASE INHIBITOR; SOTRASTAURIN; TRANSCRIPTION FACTOR RUNX2; UNCLASSIFIED DRUG;

ACUTE GRANULOCYTIC LEUKEMIA; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; CANCER COMBINATION CHEMOTHERAPY; CANCER SURVIVAL; CELL POLARITY; CELL PROLIFERATION; CELL SURVIVAL; COLORECTAL CANCER; DRUG BIOAVAILABILITY; DRUG EFFICACY; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG TOLERABILITY; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; ENZYME STRUCTURE; EWING SARCOMA; GASTROINTESTINAL STROMAL TUMOR; GENE MUTATION; GLIOBLASTOMA; HUMAN; LARGE CELL LYMPHOMA; LYMPHOMA; MYELODYSPLASTIC SYNDROME; MYELOMA; NON SMALL CELL LUNG CANCER; NONHUMAN; OSTEOSARCOMA; OVARY CANCER; OVERALL SURVIVAL; PATHOGENESIS; PERITONEUM CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN TARGETING; PTCH GENE; REVIEW; RHABDOMYOSARCOMA; SYNOVIAL SARCOMA; THETA RHYTHM; TUMOR SUPPRESSOR GENE; UVEA MELANOMA; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; CLINICAL TRIAL (TOPIC); ENZYMOLOGY; PHYSIOLOGY; SARCOMA; SIGNAL TRANSDUCTION;

ANIMALS; CLINICAL TRIALS AS TOPIC; HUMANS; PROTEIN KINASE C; SARCOMA; SIGNAL TRANSDUCTION;

EID: 84908329558     PISSN: 0304419X     EISSN: 18792561     Source Type: Journal    
DOI: 10.1016/j.bbcan.2014.10.002     Document Type: Review

References (171)

1. Fletcher C.D.M. World Health Organization., International Agency for Research on Cancer, WHO classification of tumours of soft tissue and bone 2013, IARC Press, Lyon. 4th ed.
2. N.C.I.Network Bone and Soft Tissue Sarcomas UK Incidence and Survival: 1996 to 2010 2013.
3. Burningham Z., Hashibe M., Spector L., Schiffman J.D. The epidemiology of sarcoma. Clin. Sarcoma Res. 2012, 2:14.
4. Judson I., Verweij J., Gelderblom H., Hartmann J.T., Schoffski P., Blay J.Y., Kerst J.M., Sufliarsky J., Whelan J., Hohenberger P., Krarup-Hansen A., Alcindor T., Marreaud S., Litiere S., Hermans C., Fisher C., Hogendoorn P.C., Dei Tos A.P., van der Graaf W.T., O.for the European, T.Treatment of Cancer Soft, G.Bone Sarcoma Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014, 15:415-423.
5. Akimoto K., Mizuno K., Osada S., Hirai S., Tanuma S., Suzuki K., Ohno S. A new member of the third class in the protein kinase C family, PKC lambda, expressed dominantly in an undifferentiated mouse embryonal carcinoma cell line and also in many tissues and cells. J. Biol. Chem. 1994, 269:12677-12683.
6. Sanz L., Sanchez P., Lallena M.J., Diaz-Meco M.T., Moscat J. The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation. EMBO J. 1999, 18:3044-3053.
7. Durgan J., Kaji N., Jin D., Hall A. Par6B and atypical PKC regulate mitotic spindle orientation during epithelial morphogenesis. J. Biol. Chem. 2011, 286:12461-12474.
8. Regala R.P., Weems C., Jamieson L., Copland J.A., Thompson E.A., Fields A.P. Atypical protein kinase C iota plays a critical role in human lung cancer cell growth and tumorigenicity. J. Biol. Chem. 2005, 280:31109-31115.
9. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J. Biol. Chem. 1982, 257:7847-7851.
10. Roffey J., Rosse C., Linch M., Hibbert A., McDonald N.Q., Parker P.J. Protein kinase C intervention-the state of play. Curr. Opin. Cell Biol. 2009, 21:268-279.
11. Murray N.R., Kalari K.R., Fields A.P. Protein kinase C iota expression and oncogenic signaling mechanisms in cancer. J. Cell. Physiol. 2011, 226:879-887.
12. Valkov A., Sorbye S.W., Kilvaer T.K., Donnem T., Smeland E., Bremnes R.M., Busund L.T. The prognostic impact of TGF-beta1, fascin, NF-kappaB and PKC-zeta expression in soft tissue sarcomas. PLoS One 2011, 6:e17507.
13. Brown R.E., Boyle J.L. Mesenchymal chondrosarcoma: molecular characterization by a proteomic approach, with morphogenic and therapeutic implications. Ann. Clin. Lab. Sci. 2003, 33:131-141.
14. Chen H.T., Tsou H.K., Tsai C.H., Kuo C.C., Chiang Y.K., Chang C.H., Fong Y.C., Tang C.H. Thrombin enhanced migration and MMPs expression of human chondrosarcoma cells involves PAR receptor signaling pathway. J. Cell. Physiol. 2010, 223:737-745.
15. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 1984, 308:693-698.
16. 2+-activated and phospholipid-dependent protein kinase. Proc. Natl. Acad. Sci. U. S. A. 1986, 83:8535-8539.
17. Mellor H., Parker P.J. The extended protein kinase C superfamily. Biochem. J. 1998, 332(Pt 2):281-292.
18. Vincent S., Settleman J. The PRK2 kinase is a potential effector target of both Rho and Rac GTPases and regulates actin cytoskeletal organization. Mol. Cell. Biol. 1997, 17:2247-2256.
19. Flynn P., Mellor H., Palmer R., Panayotou G., Parker P.J. Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif. J. Biol. Chem. 1998, 273:2698-2705.
20. Mukai H. The structure and function of PKN, a protein kinase having a catalytic domain homologous to that of PKC. J. Biochem. 2003, 133:17-27.
21. Rosse C., Linch M., Kermorgant S., Cameron A.J., Boeckeler K., Parker P.J. PKC and the control of localized signal dynamics. Nat. Rev. Mol. Cell Biol. 2010, 11:103-112.
22. House C., Kemp B.E. Protein kinase C contains a pseudosubstrate prototope in its regulatory domain. Science 1987, 238:1726-1728.
23. Pears C.J., Kour G., House C., Kemp B.E., Parker P.J. Mutagenesis of the pseudosubstrate site of protein kinase C leads to activation. Eur. J. Biochem. 1990, 194:89-94.
24. Kitagawa M., Shibata H., Toshimori M., Mukai H., Ono Y. The role of the unique motifs in the amino-terminal region of PKN on its enzymatic activity. Biochem. Biophys. Res. Commun. 1996, 220:963-968.
25. Bauer A.F., Sonzogni S., Meyer L., Zeuzem S., Piiper A., Biondi R.M., Neimanis S. Regulation of protein kinase C-related protein kinase 2 (PRK2) by an intermolecular PRK2-PRK2 interaction mediated by Its N-terminal domain. J. Biol. Chem. 2012, 287:20590-20602.
26. Parekh D.B., Ziegler W., Parker P.J. Multiple pathways control protein kinase C phosphorylation. EMBO J. 2000, 19:496-503.
27. Le Good J.A., Ziegler W.H., Parekh D.B., Alessi D.R., Cohen P., Parker P.J. Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1. Science 1998, 281:2042-2045.
28. Parekh D., Ziegler W., Yonezawa K., Hara K., Parker P.J. Mammalian TOR controls one of two kinase pathways acting upon nPKCdelta and nPKCepsilon. J. Biol. Chem. 1999, 274:34758-34764.
29. Guertin D.A., Stevens D.M., Thoreen C.C., Burds A.A., Kalaany N.Y., Moffat J., Brown M., Fitzgerald K.J., Sabatini D.M. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKC alpha, but not S6K1. Dev. Cell 2006, 11:859-871.
30. Facchinetti V., Ouyang W., Wei H., Soto N., Lazorchak A., Gould C., Lowry C., Newton A.C., Mao Y., Miao R.Q., Sessa W.C., Qin J., Zhang P., Su B., Jacinto E. The mammalian target of rapamycin complex 2 controls folding and stability of Akt and protein kinase C. EMBO J. 2008, 27:1932-1943.
31. Ikenoue T., Inoki K., Yang Q., Zhou X., Guan K.L. Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling. EMBO J. 2008, 27:1919-1931.
32. Cameron A.J., Escribano C., Saurin A.T., Kostelecky B., Parker P.J. PKC maturation is promoted by nucleotide pocket occupation independently of intrinsic kinase activity. Nat. Struct. Mol. Biol. 2009, 16:624-630.
33. Cameron A.J. Occupational hazards: allosteric regulation of protein kinases through the nucleotide-binding pocket. Biochem. Soc. Trans. 2011, 39:472-476.
34. Cameron A.J., Parker P.J. Protein kinase C - a family of protein kinases, allosteric effectors or both?. Adv. Enzym. Regul. 2010, 50:169-177.
35. Stensman H., Raghunath A., Larsson C. Autophosphorylation suppresses whereas kinase inhibition augments the translocation of protein kinase C alpha in response to diacylglycerol. J. Biol. Chem. 2004, 279:40576-40583.
36. Cameron A.J., Procyk K.J., Leitges M., Parker P.J. PKC alpha protein but not kinase activity is critical for glioma cell proliferation and survival. Int. J. Cancer 2008, 123:769-779.
37. Vallentin A., Lo T.C., Joubert D. A single point mutation in the V3 region affects protein kinase C alpha targeting and accumulation at cell-cell contacts. Mol. Cell. Biol. 2001, 21:3351-3363.
38. Assert R., Kotter R., Schiemann U., Goretzki P., Pfeiffer A.F. Effects of the putatively oncogenic protein kinase C alpha D294G mutation on enzymatic activity and cell growth and its occurrence in human thyroid neoplasias. Horm. Metab. Res. 2002, 34:311-317.
39. Zhu Y., Dong Q., Tan B.J., Lim W.G., Zhou S., Duan W. The PKC alpha-D294G mutant found in pituitary and thyroid tumors fails to transduce extracellular signals. Cancer Res. 2005, 65:4520-4524.
40. Linch M., Sanz-Garcia M., Soriano E., Zhang Y., Riou P., Rosse C., Cameron A., Knowles P., Purkiss A., Kjaer S., McDonald N.Q., Parker P.J. A cancer-associated mutation in atypical protein kinase C iota occurs in a substrate-specific recruitment motif. Sci. Signal. 2013, 6:ra82.
41. Linch M., Sanz-Garcia M., Rosse C., Riou P., Peel N., Madsen C.D., Sahai E., Downward J., Khwaja A., Dillon C., Roffey J., Cameron A.J., Parker P.J. Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids. Carcinogenesis 2014, 35:396-406.
42. Gatta G., van der Zwan J.M., Casali P.G., Siesling S., Dei Tos A.P., Kunkler I., Otter R., Licitra L., Mallone S., Tavilla A., Trama A., Capocaccia R. Rare cancers are not so rare: the rare cancer burden in Europe. Eur. J. Cancer 2011, 47:2493-2511.
43. Corless C.L., Barnett C.M., Heinrich M.C. Gastrointestinal stromal tumours: origin and molecular oncology. Nat. Rev. Cancer 2011, 11:865-878.
44. Demetri G.D., von Mehren M., Blanke C.D., Van den Abbeele A.D., Eisenberg B., Roberts P.J., Heinrich M.C., Tuveson D.A., Singer S., Janicek M., Fletcher J.A., Silverman S.G., Silberman S.L., Capdeville R., Kiese B., Peng B., Dimitrijevic S., Druker B.J., Corless C., Fletcher C.D., Joensuu H. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N. Engl. J. Med. 2002, 347:472-480.
45. Linch M., Claus J., Benson C. Update on imatinib for gastrointestinal stromal tumors: duration of treatment. Onco Targets Ther. 2013, 6:1011-1023.
46. Blay P., Astudillo A., Buesa J.M., Campo E., Abad M., Garcia-Garcia J., Miquel R., Marco V., Sierra M., Losa R., Lacave A., Brana A., Balbin M., Freije J.M. Protein kinase C theta is highly expressed in gastrointestinal stromal tumors but not in other mesenchymal neoplasias. Clin. Cancer Res. 2004, 10:4089-4095.
47. Duensing A., Joseph N.E., Medeiros F., Smith F., Hornick J.L., Heinrich M.C., Corless C.L., Demetri G.D., Fletcher C.D., Fletcher J.A. Protein kinase C theta (PKC theta) expression and constitutive activation in gastrointestinal stromal tumors (GISTs). Cancer Res. 2004, 64:5127-5131.
48. Liu Y., Graham C., Li A., Fisher R.J., Shaw S. Phosphorylation of the protein kinase C-theta activation loop and hydrophobic motif regulates its kinase activity, but only activation loop phosphorylation is critical to in vivo nuclear-factor-kappaB induction. Biochem. J. 2002, 361:255-265.
49. Motegi A., Sakurai S., Nakayama H., Sano T., Oyama T., Nakajima T. PKC theta, a novel immunohistochemical marker for gastrointestinal stromal tumors (GIST), especially useful for identifying KIT-negative tumors. Pathol. Int. 2005, 55:106-112.
50. Kim K.M., Kang D.W., Moon W.S., Park J.B., Park C.K., Sohn J.H., Jeong J.S., Cho M.Y., Jin S.Y., Choi J.S., Kang D.Y. PKC theta expression in gastrointestinal stromal tumor. Mod. Pathol. 2006, 19:1480-1486.
51. Wong N.A., Shelley-Fraser G. Specificity of DOG1 (K9 clone) and protein kinase C theta (clone 27) as immunohistochemical markers of gastrointestinal stromal tumour. Histopathology 2010, 57:250-258.
52. Zhu M.J., Ou W.B., Fletcher C.D., Cohen P.S., Demetri G.D., Fletcher J.A. KIT oncoprotein interactions in gastrointestinal stromal tumors: therapeutic relevance. Oncogene 2007, 26:6386-6395.
53. Ou W.B., Zhu M.J., Demetri G.D., Fletcher C.D., Fletcher J.A. Protein kinase C-theta regulates KIT expression and proliferation in gastrointestinal stromal tumors. Oncogene 2008, 27:5624-5634.
54. Stahelin R.V., Kong K.F., Raha S., Tian W., Melowic H.R., Ward K.E., Murray D., Altman A., Cho W. Protein kinase ctheta c2 domain is a phosphotyrosine binding module that plays a key role in its activation. J. Biol. Chem. 2012, 287:30518-30528.
55. Sutcliffe E.L., Bunting K.L., He Y.Q., Li J., Phetsouphanh C., Seddiki N., Zafar A., Hindmarsh E.J., Parish C.R., Kelleher A.D., McInnes R.L., Taya T., Milburn P.J., Rao S. Chromatin-associated protein kinase C-theta regulates an inducible gene expression program and microRNAs in human T lymphocytes. Mol. Cell 2011, 41:704-719.
56. Ottaviani G., Jaffe N. The epidemiology of osteosarcoma. Cancer Treat. Res. 2009, 152:3-13.
57. Perego P., Casati G., Gambetta R.A., Soranzo C., Zunino F. Effect of modulation of protein kinase C activity on cisplatin cytotoxicity in cisplatin-resistant and cisplatin-sensitive human osteosarcoma cells. Cancer Lett. 1993, 72:53-58.
58. Fujita M., Sugama S., Nakai M., Takenouchi T., Wei J., Urano T., Inoue S., Hashimoto M. alpha-Synuclein stimulates differentiation of osteosarcoma cells: relevance to down-regulation of proteasome activity. J. Biol. Chem. 2007, 282:5736-5748.
59. Ren L., Hong S.H., Cassavaugh J., Osborne T., Chou A.J., Kim S.Y., Gorlick R., Hewitt S.M., Khanna C. The actin-cytoskeleton linker protein ezrin is regulated during osteosarcoma metastasis by PKC. Oncogene 2009, 28:792-802.
60. Kim H.J., Kim J.H., Bae S.C., Choi J.Y., Kim H.J., Ryoo H.M. The protein kinase C pathway plays a central role in the fibroblast growth factor-stimulated expression and transactivation activity of Runx2. J. Biol. Chem. 2003, 278:319-326.
61. Kim B.G., Kim H.J., Park H.J., Kim Y.J., Yoon W.J., Lee S.J., Ryoo H.M., Cho J.Y. Runx2 phosphorylation induced by fibroblast growth factor-2/protein kinase C pathways. Proteomics 2006, 6:1166-1174.
62. Levanon D., Negreanu V., Bernstein Y., Bar-Am I., Avivi L., Groner Y. AML1, AML2, and AML3, the human members of the runt domain gene-family: cDNA structure, expression, and chromosomal localization. Genomics 1994, 23:425-432.
63. Andela V.B., Siddiqui F., Groman A., Rosier R.N. An immunohistochemical analysis to evaluate an inverse correlation between Runx2/Cbfa1 and NF kappa B in human osteosarcoma. J. Clin. Pathol. 2005, 58:328-330.
64. Kurek K.C., Del Mare S., Salah Z., Abdeen S., Sadiq H., Lee S.H., Gaudio E., Zanesi N., Jones K.B., DeYoung B., Amir G., Gebhardt M., Warman M., Stein G.S., Stein J.L., Lian J.B., Aqeilan R.I. Frequent attenuation of the WWOX tumor suppressor in osteosarcoma is associated with increased tumorigenicity and aberrant RUNX2 expression. Cancer Res. 2010, 70:5577-5586.
65. Martin J.W., Zielenska M., Stein G.S., van Wijnen A.J., Squire J.A. The role of RUNX2 in osteosarcoma oncogenesis. Sarcoma 2011, 2011:282745.
66. Kobayashi E., Nakano H., Morimoto M., Tamaoki T. Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem. Biophys. Res. Commun. 1989, 159:548-553.
67. Soltoff S.P. Rottlerin: an inappropriate and ineffective inhibitor of PKCdelta. Trends Pharmacol. Sci. 2007, 28:453-458.
68. Hong S.H., Osborne T., Ren L., Briggs J., Mazcko C., Burkett S.S., Khanna C. Protein kinase C regulates ezrin-radixin-moesin phosphorylation in canine osteosarcoma cells. Vet. Comp. Oncol. 2011, 9:207-218.
69. Ng T., Parsons M., Hughes W.E., Monypenny J., Zicha D., Gautreau A., Arpin M., Gschmeissner S., Verveer P.J., Bastiaens P.I., Parker P.J. Ezrin is a downstream effector of trafficking PKC-integrin complexes involved in the control of cell motility. EMBO J. 2001, 20:2723-2741.
70. Zhang Y., Zhang L., Zhang G., Li S., Duan J., Cheng J., Ding G., Zhou C., Zhang J., Luo P., Cai D., Kuang L., Zhou Y., Tong L., Yu X., Zhang L., Xu L., Yu L., Shi X., Ke A. Osteosarcoma metastasis: prospective role of ezrin. Tumour Biol. 2014, 35:5055-5059.
71. Fievet B.T., Gautreau A., Roy C., Del Maestro L., Mangeat P., Louvard D., Arpin M. Phosphoinositide binding and phosphorylation act sequentially in the activation mechanism of ezrin. J. Cell Biol. 2004, 164:653-659.
72. Kawamoto T., Akisue T., Kishimoto K., Hara H., Imabori M., Fujimoto T., Kurosaka M., Hitora T., Kawaguchi Y., Yamamoto T. Inhibition of PKC alpha activation in human bone and soft tissue sarcoma cells by the selective PKC inhibitor PKC412. Anticancer Res. 2008, 28:825-832.
73. Ognjanovic S., Linabery A.M., Charbonneau B., Ross J.A. Trends in childhood rhabdomyosarcoma incidence and survival in the United States, 1975-2005. Cancer 2009, 115:4218-4226.
74. Barr F.G., Galili N., Holick J., Biegel J.A., Rovera G., Emanuel B.S. Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Nat. Genet. 1993, 3:113-117.
75. Missiaglia E., Williamson D., Chisholm J., Wirapati P., Pierron G., Petel F., Concordet J.P., Thway K., Oberlin O., Pritchard-Jones K., Delattre O., Delorenzi M., Shipley J. PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification. J. Clin. Oncol. 2012, 30:1670-1677.
76. Hanania N., Lezenes J.R., Castagna M. Tumorigenicity-associated expression of protein kinase C isoforms in rhabdomyosarcoma-derived cells. FEBS Lett. 1992, 303:15-18.
77. Cen L., Arnoczky K.J., Hsieh F.C., Lin H.J., Qualman S.J., Yu S., Xiang H., Lin J. Phosphorylation profiles of protein kinases in alveolar and embryonal rhabdomyosarcoma. Mod. Pathol. 2007, 20:936-946.
78. Kikuchi K., Soundararajan A., Zarzabal L.A., Weems C.R., Nelon L.D., Hampton S.T., Michalek J.E., Rubin B.P., Fields A.P., Keller C. Protein kinase C iota as a therapeutic target in alveolar rhabdomyosarcoma. Oncogene 2013, 32:286-295.
79. Atwood S.X., Li M., Lee A., Tang J.Y., Oro A.E. GLI activation by atypical protein kinase C iota/lambda regulates the growth of basal cell carcinomas. Nature 2013, 494:484-488.
80. Atwood S.X., Oro A.E. "Atypical" regulation of Hedgehog-dependent cancers. Cancer Cell 2014, 25:133-134.
81. Hahn H., Wojnowski L., Zimmer A.M., Hall J., Miller G., Zimmer A. Rhabdomyosarcomas and radiation hypersensitivity in a mouse model of Gorlin syndrome. Nat. Med. 1998, 4:619-622.
82. Cajaiba M.M., Bale A.E., Alvarez-Franco M., McNamara J., Reyes-Mugica M. Rhabdomyosarcoma, Wilms tumor, and deletion of the patched gene in Gorlin syndrome. Nat. Clin. Pract. Oncol. 2006, 3:575-580.
83. Gorlin R.J. Nevoid basal cell carcinoma (Gorlin) syndrome: unanswered issues. J. Lab. Clin. Med. 1999, 134:551-552.
84. Tostar U., Malm C.J., Meis-Kindblom J.M., Kindblom L.G., Toftgard R., Unden A.B. Deregulation of the Hedgehog signalling pathway: a possible role for the PTCH and SUFU genes in human rhabdomyoma and rhabdomyosarcoma development. J. Pathol. 2006, 208:17-25.
85. Bridge J.A., Liu J., Weibolt V., Baker K.S., Perry D., Kruger R., Qualman S., Barr F., Sorensen P., Triche T., Suijkerbuijk R. Novel genomic imbalances in embryonal rhabdomyosarcoma revealed by comparative genomic hybridization and fluorescence in situ hybridization: an intergroup rhabdomyosarcoma study. Genes Chromosomes Cancer 2000, 27:337-344.
86. Gurney J.G., Davis S., Severson R.K., Fang J.Y., Ross J.A., Robison L.L. Trends in cancer incidence among children in the U.S. Cancer 1996, 78:532-541.
87. Miser J.S., Krailo M.D., Tarbell N.J., Link M.P., Fryer C.J., Pritchard D.J., Gebhardt M.C., Dickman P.S., Perlman E.J., Meyers P.A., Donaldson S.S., Moore S., Rausen A.R., Vietti T.J., Grier H.E. Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide-a Children's Cancer Group and Pediatric Oncology Group study. J. Clin. Oncol. 2004, 22:2873-2876.
88. Delattre O., Zucman J., Plougastel B., Desmaze C., Melot T., Peter M., Kovar H., Joubert I., de Jong P., Rouleau G., et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 1992, 359:162-165.
89. Surdez D., Benetkiewicz M., Perrin V., Han Z.Y., Pierron G., Ballet S., Lamoureux F., Redini F., Decouvelaere A.V., Daudigeos-Dubus E., Geoerger B., de Pinieux G., Delattre O., Tirode F. Targeting the EWSR1-FLI1 oncogene-induced protein kinase PKC-beta abolishes ewing sarcoma growth. Cancer Res. 2012, 72:4494-4503.
90. Metzger E., Imhof A., Patel D., Kahl P., Hoffmeyer K., Friedrichs N., Muller J.M., Greschik H., Kirfel J., Ji S., Kunowska N., Beisenherz-Huss C., Gunther T., Buettner R., Schule R. Phosphorylation of histone H3T6 by PKCbeta(I) controls demethylation at histone H3K4. Nature 2010, 464:792-796.
91. Greer Y.E., Fields A.P., Brown A.M., Rubin J.S. Atypical protein kinase C iota is required for Wnt3a-dependent neurite outgrowth and binds to phosphorylated dishevelled2. J. Biol. Chem. 2013, 288:9438-9446.
92. Anastas J.N., Moon R.T. WNT signalling pathways as therapeutic targets in cancer. Nat. Rev. Cancer 2013, 13:11-26.
93. Endo Y., Rubin J.S. Wnt signaling and neurite outgrowth: insights and questions. Cancer Sci. 2007, 98:1311-1317.
94. Greer Y.E., Rubin J.S. Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a-dependent neurite outgrowth. J. Cell Biol. 2011, 192:993-1004.
95. Kadoch C., Crabtree G.R. Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma. Cell 2013, 153:71-85.
96. Chou Y.T., Lee C.C., Hsiao S.H., Lin S.E., Lin S.C., Chung C.H., Chung C.H., Kao Y.R., Wang Y.H., Chen C.T., Wei Y.H., Wu C.W. The emerging role of SOX2 in cell proliferation and survival and its crosstalk with oncogenic signaling in lung cancer. Stem Cells 2013, 31:2607-2619.
97. Justilien V., Walsh M.P., Ali S.A., Thompson E.A., Murray N.R., Fields A.P. The PRKCI and SOX2 oncogenes are coamplified and cooperate to activate Hedgehog signaling in lung squamous cell carcinoma. Cancer Cell 2014, 25:139-151.
98. Messerschmidt A., Macieira S., Velarde M., Badeker M., Benda C., Jestel A., Brandstetter H., Neuefeind T., Blaesse M. Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif. J. Mol. Biol. 2005, 352:918-931.
99. Leonard T.A., Rozycki B., Saidi L.F., Hummer G., Hurley J.H. Crystal structure and allosteric activation of protein kinase C beta II. Cell 2011, 144:55-66.
100. Xu Z.B., Chaudhary D., Olland S., Wolfrom S., Czerwinski R., Malakian K., Lin L., Stahl M.L., Joseph-McCarthy D., Benander C., Fitz L., Greco R., Somers W.S., Mosyak L. Catalytic domain crystal structure of protein kinase C-theta (PKC theta). J. Biol. Chem. 2004, 279:50401-50409.
101. Newton A.C. Protein kinase C: structure, function, and regulation. J. Biol. Chem. 1995, 270:28495-28498.
102. Cameron A.J., Linch M.D., Saurin A.T., Escribano C., Parker P.J. mTORC2 targets AGC kinases through Sin1-dependent recruitment. Biochem. J. 2011, 439:287-297.
103. Mochly-Rosen D., Khaner H., Lopez J. Identification of intracellular receptor proteins for activated protein kinase C. Proc. Natl. Acad. Sci. U. S. A. 1991, 88:3997-4000.
104. Ma C.X., Ellis M.J., Petroni G.R., Guo Z., Cai S.R., Ryan C.E., Craig Lockhart A., Naughton M.J., Pluard T.J., Brenin C.M., Picus J., Creekmore A.N., Mwandoro T., Yarde E.R., Reed J., Ebbert M., Bernard P.S., Watson M., Doyle L.A., Dancey J., Piwnica-Worms H., Fracasso P.M. A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer. Breast Cancer Res. Treat. 2013, 137:483-492.
105. Fischer T., Stone R.M., Deangelo D.J., Galinsky I., Estey E., Lanza C., Fox E., Ehninger G., Feldman E.J., Schiller G.J., Klimek V.M., Nimer S.D., Gilliland D.G., Dutreix C., Huntsman-Labed A., Virkus J., Giles F.J. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J. Clin. Oncol. 2010, 28:4339-4345.
106. Reichardt P., Pink D., Lindner T., Heinrich M.C., Cohen P.S., Wang Y., Yu R., Tsyrlova A., Dimitrijevic S., Blanke C. A phase I/II trial of the oral PKC-inhibitor PKC412 (PKC) in combination with imatinib mesylate (IM) in patients (pts) with gastrointestinal stromal tumor (GIST) refractory to IM. J. Clin. Oncol. 2005, 23.
107. Propper D.J., McDonald A.C., Man A., Thavasu P., Balkwill F., Braybrooke J.P., Caponigro F., Graf P., Dutreix C., Blackie R., Kaye S.B., Ganesan T.S., Talbot D.C., Harris A.L., Twelves C. Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C. J. Clin. Oncol. 2001, 19:1485-1492.
108. Millward M.J., House C., Bowtell D., Webster L., Olver I.N., Gore M., Copeman M., Lynch K., Yap A., Wang Y., Cohen P.S., Zalcberg J. The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study. Br. J. Cancer 2006, 95:829-834.
109. Carducci M.A., Musib L., Kies M.S., Pili R., Truong M., Brahmer J.R., Cole P., Sullivan R., Riddle J., Schmidt J., Enas N., Sinha V., Thornton D.E., Herbst R.S. Phase I dose escalation and pharmacokinetic study of enzastaurin, an oral protein kinase C beta inhibitor, in patients with advanced cancer. J. Clin. Oncol. 2006, 24:4092-4099.
110. Robertson M.J., Kahl B.S., Vose J.M., de Vos S., Laughlin M., Flynn P.J., Rowland K., Cruz J.C., Goldberg S.L., Musib L., Darstein C., Enas N., Kutok J.L., Aster J.C., Neuberg D., Savage K.J., LaCasce A., Thornton D., Slapak C.A., Shipp M.A. Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma. J. Clin. Oncol. 2007, 25:1741-1746.
111. Glimelius B., Lahn M., Gawande S., Cleverly A., Darstein C., Musib L., Liu Y., Spindler K.L., Frodin J.E., Berglund A., Bystrom P., Qvortrup C., Jakobsen A., Pfeiffer P. A window of opportunity phase II study of enzastaurin in chemonaive patients with asymptomatic metastatic colorectal cancer. Ann. Oncol. 2010, 21:1020-1026.
112. Usha L., Sill M.W., Darcy K.M., Benbrook D.M., Hurteau J.A., Michelin D.P., Mannel R.S., Hanjani P., De Geest K., Godwin A.K. A Gynecologic Oncology Group phase II trial of the protein kinase C-beta inhibitor, enzastaurin and evaluation of markers with potential predictive and prognostic value in persistent or recurrent epithelial ovarian and primary peritoneal malignancies. Gynecol. Oncol. 2011, 121:455-461.
113. Jourdan E., Leblond V., Maisonneuve H., Benhadji K.A., Hossain A.M., Nguyen T.S., Wooldridge J.E., Moreau P. A multicenter phase II study of single-agent enzastaurin in previously treated multiple myeloma. Leuk. Lymphoma 2014, 55:2013-2017.
114. Oh Y., Herbst R.S., Burris H., Cleverly A., Musib L., Lahn M., Bepler G. Enzastaurin, an oral serine/threonine kinase inhibitor, as second- or third-line therapy of non-small-cell lung cancer. J. Clin. Oncol. 2008, 26:1135-1141.
115. Vergote I.B., Chekerov R., Amant F., Harter P., Casado A., Emerich J., Bauknecht T., Mansouri K., Myrand S.P., Nguyen T.S., Shi P., Sehouli J. Randomized, phase II, placebo-controlled, double-blind study with and without enzastaurin in combination with paclitaxel and carboplatin as first-line treatment followed by maintenance treatment in advanced ovarian cancer. J. Clin. Oncol. 2013, 31:3127-3132.
116. Socinski M.A., Raju R.N., Stinchcombe T., Kocs D.M., Couch L.S., Barrera D., Rousey S.R., Choksi J.K., Jotte R., Patt D.A., Periman P.O., Schlossberg H.R., Weissman C.H., Wang Y., Asmar L., Pritchard S., Bromund J., Peng G., Treat J., Obasaju C.K. Randomized, phase II trial of pemetrexed and carboplatin with or without enzastaurin versus docetaxel and carboplatin as first-line treatment of patients with stage IIIB/IV non-small cell lung cancer. J. Thorac. Oncol. 2010, 5:1963-1969.
117. Wick W., Steinbach J.P., Platten M., Hartmann C., Wenz F., von Deimling A., Shei P., Moreau-Donnet V., Stoffregen C., Combs S.E. Enzastaurin before and concomitant with radiation therapy, followed by enzastaurin maintenance therapy, in patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation. Neuro-Oncology 2013, 15:1405-1412.
118. Plimack E.R., Tan T., Wong Y.N., von Mehren M.M., Malizzia L., Roethke S.K., Litwin S., Li T., Hudes G.R., Haas N.B. A phase I study of temsirolimus and Bryostatin-1 in patients with metastatic renal cell carcinoma and soft tissue sarcoma. Oncologist 2014, 19:354-355.
119. Ajani J.A., Jiang Y., Faust J., Chang B.B., Ho L., Yao J.C., Rousey S., Dakhil S., Cherny R.C., Craig C., Bleyer A. A multi-center phase II study of sequential paclitaxel and Bryostatin-1 (NSC 339555) in patients with untreated, advanced gastric or gastroesophageal junction adenocarcinoma. Investig. New Drugs 2006, 24:353-357.
120. Mansfield A.S., Fields A.P., Jatoi A., Qi Y., Adjei A.A., Erlichman C., Molina J.R. Phase I dose escalation study of the PKC iota inhibitor aurothiomalate for advanced non-small-cell lung cancer, ovarian cancer, and pancreatic cancer. Anti-Cancer Drugs 2013, 24:1079-1083.
121. Yuen A.R., Halsey J., Fisher G.A., Holmlund J.T., Geary R.S., Kwoh T.J., Dorr A., Sikic B.I. Phase I study of an antisense oligonucleotide to protein kinase C-alpha (ISIS 3521/CGP 64128A) in patients with cancer. Clin. Cancer Res. 1999, 5:3357-3363.
122. Advani R., Lum B.L., Fisher G.A., Halsey J., Geary R.S., Holmlund J.T., Kwoh T.J., Dorr F.A., Sikic B.I. A phase I trial of aprinocarsen (ISIS 3521/LY900003), an antisense inhibitor of protein kinase C-alpha administered as a 24-hour weekly infusion schedule in patients with advanced cancer. Investig. New Drugs 2005, 23:467-477.
123. Rao S., Watkins D., Cunningham D., Dunlop D., Johnson P., Selby P., Hancock B.W., Fegan C., Culligan D., Schey S., Morris T.C., Lissitchkov T., Oliver J.W., Holmlund J.T. Phase II study of ISIS 3521, an antisense oligodeoxynucleotide to protein kinase C alpha, in patients with previously treated low-grade non-Hodgkin's lymphoma. Ann. Oncol. 2004, 15:1413-1418.
124. Marshall J.L., Eisenberg S.G., Johnson M.D., Hanfelt J., Dorr F.A., El-Ashry D., Oberst M., Fuxman Y., Holmlund J., Malik S. A phase II trial of ISIS 3521 in patients with metastatic colorectal cancer. Clin. Colorectal Cancer 2004, 4:268-274.
125. Grossman S.A., Alavi J.B., Supko J.G., Carson K.A., Priet R., Dorr F.A., Grundy J.S., Holmlund J.T. Efficacy and toxicity of the antisense oligonucleotide aprinocarsen directed against protein kinase C-alpha delivered as a 21-day continuous intravenous infusion in patients with recurrent high-grade astrocytomas. Neuro-Oncology 2005, 7:32-40.
126. Advani R., Peethambaram P., Lum B.L., Fisher G.A., Hartmann L., Long H.J., Halsey J., Holmlund J.T., Dorr A., Sikic B.I. A phase II trial of aprinocarsen, an antisense oligonucleotide inhibitor of protein kinase C alpha, administered as a 21-day infusion to patients with advanced ovarian carcinoma. Cancer 2004, 100:321-326.
127. Yuen A., Halsey J., Fisher G., Advan i.R., Moore M., Saleh M., Riych P., Harker G., Ahmed C., Jones J., Polikoff W., Keiser T., Geary R., Kwoh T., Holmlund J., Dorr A., Sikic B.I. Phase I/II trial of ISIS 3521, an antisense inhibitor of protein kinase C α, with carboplatin and paclitaxel in non-small cell lung cancer. J. Clin. Oncol. 2001, 20.
128. Paz-Ares L., Douillard J.Y., Koralewski P., Manegold C., Smit E.F., Reyes J.M., Chang G.C., John W.J., Peterson P.M., Obasaju C.K., Lahn M., Gandara D.R. Phase III study of gemcitabine and cisplatin with or without aprinocarsen, a protein kinase C-alpha antisense oligonucleotide, in patients with advanced-stage non-small-cell lung cancer. J. Clin. Oncol. 2006, 24:1428-1434.
129. Schultheis B., Strumberg D., Santel A., Gebhardt F., Khan M., Keil O., Giese K., Kaufmann J. First-in-human phase I study of the liposomal RNAi therapeutic Atu027 in patients with advanced cancer. J. Clin. Oncol. 2013, 31.
130. Medina J.R. Selective 3-phosphoinositide-dependent kinase 1 (PDK1) inhibitors: dissecting the function and pharmacology of PDK1. J. Med. Chem. 2013, 56:2726-2737.
131. Hudes G., Carducci M., Tomczak P., Dutcher J., Figlin R., Kapoor A., Staroslawska E., Sosman J., McDermott D., Bodrogi I., Kovacevic Z., Lesovoy V., Schmidt-Wolf I.G., Barbarash O., Gokmen E., O'Toole T., Lustgarten S., Moore L., Motzer R.J., Global A.T. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N. Engl. J. Med. 2007, 356:2271-2281.
132. Baselga J., Campone M., Piccart M., Burris H.A., Rugo H.S., Sahmoud T., Noguchi S., Gnant M., Pritchard K.I., Lebrun F., Beck J.T., Ito Y., Yardley D., Deleu I., Perez A., Bachelot T., Vittori L., Xu Z., Mukhopadhyay P., Lebwohl D., Hortobagyi G.N. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N. Engl. J. Med. 2012, 366:520-529.
133. Demetri G.D., Chawla S.P., Ray-Coquard I., Le Cesne A., Staddon A.P., Milhem M.M., Penel N., Riedel R.F., Bui-Nguyen B., Cranmer L.D., Reichardt P., Bompas E., Alcindor T., Rushing D., Song Y., Lee R.M., Ebbinghaus S., Eid J.E., Loewy J.W., Haluska F.G., Dodion P.F., Blay J.Y. Results of an international randomized phase III trial of the mammalian target of rapamycin inhibitor ridaforolimus versus placebo to control metastatic sarcomas in patients after benefit from prior chemotherapy. J. Clin. Oncol. 2013, 31:2485-2492.
134. Debiec-Rychter M., Cools J., Dumez H., Sciot R., Stul M., Mentens N., Vranckx H., Wasag B., Prenen H., Roesel J., Hagemeijer A., Van Oosterom A., Marynen P. Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology 2005, 128:270-279.
135. Hanauske A.R., Oberschmidt O., Hanauske-Abel H., Lahn M.M., Eismann U. Antitumor activity of enzastaurin (LY317615.HCl) against human cancer cell lines and freshly explanted tumors investigated in in-vitro [corrected] soft-agar cloning experiments. Investig. New Drugs 2007, 25:205-210.
136. Liu Y., Su W., Thompson E.A., Leitges M., Murray N.R., Fields A.P. Protein kinase CbetaII regulates its own expression in rat intestinal epithelial cells and the colonic epithelium in vivo. J. Biol. Chem. 2004, 279:45556-45563.
137. Keyes K., Cox K., Treadway P., Mann L., Shih C., Faul M.M., Teicher B.A. An in vitro tumor model: analysis of angiogenic factor expression after chemotherapy. Cancer Res. 2002, 62:5597-5602.
138. Fine H.A., Kim L., Royce C. Results from phase II trial of enzastaurin (LY317615) in patients with recurrent high grade gliomas. J. Clin. Oncol. 2005, 23.
139. Stupp R., Mason W.P., van den Bent M.J., Weller M., Fisher B., Taphoorn M.J., Belanger K., Brandes A.A., Marosi C., Bogdahn U., Curschmann J., Janzer R.C., Ludwin S.K., Gorlia T., Allgeier A., Lacombe D., Cairncross J.G., Eisenhauer E., Mirimanoff R.O., R.European Organisation for, T.Treatment of Cancer Brain, G.Radiotherapy, G.National Cancer Institute of Canada Clinical Trials Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005, 352:987-996.
140. Wagner J., von Matt P., Sedrani R., Albert R., Cooke N., Ehrhardt C., Geiser M., Rummel G., Stark W., Strauss A., Cowan-Jacob S.W., Beerli C., Weckbecker G., Evenou J.P., Zenke G., Cottens S. Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes. J. Med. Chem. 2009, 52:6193-6196.
141. Wu X., Li J., Zhu M., Fletcher J.A., Hodi F.S. Protein kinase C inhibitor AEB071 targets ocular melanoma harboring GNAQ mutations via effects on the PKC/Erk1/2 and PKC/NF-kappaB pathways. Mol. Cancer Ther. 2012, 11:1905-1914.
142. Cerne J.Z., Hartig S.M., Hamilton M.P., Chew S.A., Mitsiades N., Poulaki V., McGuire S.E. Protein kinase C inhibitors sensitize GNAQ mutant uveal melanoma cells to ionizing radiation. Invest. Ophthalmol. Vis. Sci. 2014, 55:2130-2139.
143. Musi E., Ambrosini G., De Stanchina E., Schwartz G.K. The phosphoinositide 3-kinase alpha selective inhibitor, BYL719, enhances the effect of the protein kinase C inhibitor, AEB071, in GNAQ/GNA11 mutant uveal melanoma cells. Mol. Cancer Ther. 2014, 13:1044-1053.
144. Chen X., Wu Q., Tan L., Porter D., Jager M.J., Emery C., Bastian B.C. Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations. Oncogene 2014, 33:4724-4734.
145. Friman S., Arns W., Nashan B., Vincenti F., Banas B., Budde K., Cibrik D., Chan L., Klempnauer J., Mulgaonkar S., Nicholson M., Wahlberg J., Wissing K.M., Abrams K., Witte S., Woodle E.S. Sotrastaurin, a novel small molecule inhibiting protein-kinase C: randomized phase II study in renal transplant recipients. Am. J. Transplant. 2011, 11:1444-1455.
146. Budde K., Sommerer C., Becker T., Asderakis A., Pietruck F., Grinyo J.M., Rigotti P., Dantal J., Ng J., Barten M.J., Weber M. Sotrastaurin, a novel small molecule inhibiting protein kinase C: first clinical results in renal-transplant recipients. Am. J. Transplant. 2010, 10:571-581.
147. Tedesco-Silva H., Kho M.M., Hartmann A., Vitko S., Russ G., Rostaing L., Budde K., Campistol J.M., Eris J., Krishnan I., Gopalakrishnan U., Klupp J. Sotrastaurin in calcineurin inhibitor-free regimen using Everolimus in de novo kidney transplant recipients. Am. J. Transplant. 2013, 13:1757-1768.
148. Kjaer S., Linch M., Purkiss A., Kostelecky B., Knowles P.P., Rosse C., Riou P., Soudy C., Kaye S., Patel B., Soriano E., Murray-Rust J., Barton C., Dillon C., Roffey J., Parker P.J., McDonald N.Q. Adenosine-binding motif mimicry and cellular effects of a thieno[2,3-d]pyrimidine-based chemical inhibitor of atypical protein kinase C isoenzymes. Biochem. J. 2013, 451:329-342.
149. Soudy C., Stanway E., Patel B., Barton C., Barnard M., Pang L., Owen P., Turnbull A., Ruggeri B.A., Dorsey B.D., Ator M.A., Ott G.R., Linch M., Riou P., Parker P.J., Kjaer S., Dillon C., McDonald N.Q., Roffey J. Identification and Characterization of Small Molecule Thieno[3,2-d]pyrimidine Inhibitors of Protein Kinase C Iota (PKCι) AACR, LB-99 2014.
150. Linch M., Sanz-Garcia M., Rosse C., Riou P., Peel N., Madsen C.D., Sahai E., Downward J., Khwaja A., Dillon C., Roffey J., Cameron A.J., Parker P.J. Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids. Carcinogenesis 2014, 35:396-406.
151. Oda Y., Sakamoto A., Satio T., Kawauchi S., Iwamoto Y., Tsuneyoshi M. Molecular abnormalities of p53, MDM2, and H-ras in synovial sarcoma. Mod. Pathol. 2000, 13:994-1004.
152. Stratton M.R., Fisher C., Gusterson B.A., Cooper C.S. Detection of point mutations in N-ras and K-ras genes of human embryonal rhabdomyosarcomas using oligonucleotide probes and the polymerase chain reaction. Cancer Res. 1989, 49:6324-6327.
153. Bohle R.M., Brettreich S., Repp R., Borkhardt A., Kosmehl H., Altmannsberger H.M. Single somatic ras gene point mutation in soft tissue malignant fibrous histiocytomas. Am. J. Pathol. 1996, 148:731-738.
154. Pettit G.R., Fujii Y., Hasler J.A., Schmidt J.M. Isolation and characterization of palystatins A-D. J. Nat. Prod. 1982, 45:272-276.
155. Hahn H., Wicking C., Zaphiropoulous P.G., Gailani M.R., Shanley S., Chidambaram A., Vorechovsky I., Holmberg E., Unden A.B., Gillies S., Negus K., Smyth I., Pressman C., Leffell D.J., Gerrard B., Goldstein A.M., Dean M., Toftgard R., Chenevix-Trench G., Wainwright B., Bale A.E. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell 1996, 85:841-851.
156. Barr P.M., Lazarus H.M., Cooper B.W., Schluchter M.D., Panneerselvam A., Jacobberger J.W., Hsu J.W., Janakiraman N., Simic A., Dowlati A., Remick S.C. Phase II study of Bryostatin 1 and vincristine for aggressive non-Hodgkin lymphoma relapsing after an autologous stem cell transplant. Am. J. Hematol. 2009, 84:484-487.
157. Qvit N., Mochly-Rosen D. Highly specific modulators of protein kinase C localization: applications to heart failure. Drug Discov. Today Dis. Mech. 2010, 7:e87-e93.
158. Ikeno F., Inagaki K., Rezaee M., Mochly-Rosen D. Impaired perfusion after myocardial infarction is due to reperfusion-induced deltaPKC-mediated myocardial damage. Cardiovasc. Res. 2007, 73:699-709.
159. Lincoff A.M. Selective Inhibition of Delta Protein Kinase C to Reduce Infarct Size after Primary Percutaneous Intervention for Acute Myocardial Infarction: The PROTECTION-AMI Phase IIB Clinical Trial 2011, American College Cardiology - Late Breaking Clinical Trial.
160. Stallings-Mann M., Jamieson L., Regala R.P., Weems C., Murray N.R., Fields A.P. A novel small-molecule inhibitor of protein kinase C iota blocks transformed growth of non-small-cell lung cancer cells. Cancer Res. 2006, 66:1767-1774.
161. Messori L., Marcon G. Gold complexes as antitumor agents. Met. Ions Biol. Syst. 2004, 42:385-424.
162. Erdogan E., Lamark T., Stallings-Mann M., Lee J., Pellecchia M., Thompson E.A., Johansen T., Fields A.P. Aurothiomalate inhibits transformed growth by targeting the PB1 domain of protein kinase C iota. J. Biol. Chem. 2006, 281:28450-28459.
163. Regala R.P., Thompson E.A., Fields A.P. Atypical protein kinase C iota expression and aurothiomalate sensitivity in human lung cancer cells. Cancer Res. 2008, 68:5888-5895.
164. Song H.F., Tang Z.M., Yuan S.J., Zhu B.Z. Application of secondary structure prediction in antisense drug design targeting protein kinase C-alpha mRNA and QSAR analysis. Acta Pharmacol. Sin. 2000, 21:80-86.
165. Song H.F., Tang Z.M., Yuan S.J., Zhu B.Z., Liu X.W. Antisense candidates against protein kinase C-alpha designed based on phylogenesis and simulant structure of mRNA. Acta Pharmacol. Sin. 2003, 24:269-276.
166. Aleku M., Schulz P., Keil O., Santel A., Schaeper U., Dieckhoff B., Janke O., Endruschat J., Durieux B., Roder N., Loffler K., Lange C., Fechtner M., Mopert K., Fisch G., Dames S., Arnold W., Jochims K., Giese K., Wiedenmann B., Scholz A., Kaufmann J. Atu027, a liposomal small interfering RNA formulation targeting protein kinase N3, inhibits cancer progression. Cancer Res. 2008, 68:9788-9798.
167. Storey J.D., Tibshirani R. Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:9440-9445.
168. Nakayama R., Nemoto T., Takahashi H., Ohta T., Kawai A., Seki K., Yoshida T., Toyama Y., Ichikawa H., Hasegawa T. Gene expression analysis of soft tissue sarcomas: characterization and reclassification of malignant fibrous histiocytoma. Mod. Pathol. 2007, 20:749-759.
169. Subramanian S., West R.B., Marinelli R.J., Nielsen T.O., Rubin B.P., Goldblum J.R., Patel R.M., Zhu S., Montgomery K., Ng T.L., Corless C.L., Heinrich M.C., van de Rijn M. The gene expression profile of extraskeletal myxoid chondrosarcoma. J. Pathol. 2005, 206:433-444.
170. Detwiller K.Y., Fernando N.T., Segal N.H., Ryeom S.W., D'Amore P.A., Yoon S.S. Analysis of hypoxia-related gene expression in sarcomas and effect of hypoxia on RNA interference of vascular endothelial cell growth factor A. Cancer Res. 2005, 65:5881-5889.
171. Henderson S.R., Guiliano D., Presneau N., McLean S., Frow R., Vujovic S., Anderson J., Sebire N., Whelan J., Athanasou N., Flanagan A.M., Boshoff C. A molecular map of mesenchymal tumors. Genome Biol. 2005, 6:R76.