JBNB  Vol.3 No.2 , April 2012
Conjugation of Magnetite Nanoparticles with Melanogenesis Substrate, NPrCAP Provides Melanoma Targeted, in Situ Peptide Vaccine Immunotherapy through HSP Production by Chemo-Thermotherapy
ABSTRACT
In order to develop melanoma-targeted in situ peptide vaccine immunotherapy, magnetite nanoparticles were conjugated with a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP). Magnetite nanoparticles introduced thermotherapy which caused non-apoptotic cell death and generation of heat shock protein (HSP) upon exposure to alternating magnetic field (AMF). NPrCAP was expected to develop a melanoma-targeted therapeutic drug because of its selective incorporation into melanoma cells and production of highly reactive free radicals, that result in not only oxidative stress but also apoptotic cell death by reacting with tyrosinase.

Cite this paper
K. Jimbow, Y. Tamura, A. Yoneta, T. Kamiya, I. Ono, T. Yamashita, A. Ito, H. Honda, K. Wakamatsu, S. Ito, S. Nohara, E. Nakayama and T. Kobayashi, "Conjugation of Magnetite Nanoparticles with Melanogenesis Substrate, NPrCAP Provides Melanoma Targeted, in Situ Peptide Vaccine Immunotherapy through HSP Production by Chemo-Thermotherapy," Journal of Biomaterials and Nanobiotechnology, Vol. 3 No. 2, 2012, pp. 140-153. doi: 10.4236/jbnb.2012.32020.
References
[1]   C. M. Balch, A. C. Buzaid, S. J. Soong, M. B. Atkins, N. Cascinelli, D. G. Coit, I. D. Fleming, J. E. Gershenwald, A. Houghton Jr., J. M. Kirkwood, K. M. McMasters, M. F. Mihm, D. L. Morton, D. S. Reintgen, M. I. Ross, A. Sober, J. A. Thompson and J. F. Thompson, “Final Version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma,” Journal of Clinical Oncology, Vol. 19, No. 16, 2001, pp. 3635-3648.

[2]   A. Ito, M. Shinkai, H. Honda and T. Kobayashi, “Medical Application of Functionalized Magnetic Nanoparticles,” Journal of Bioscience and Bioengineering, Vol. 100, No. 1, 2005, pp. 1-11. doi:10.1263/jbb.100.1

[3]   N. Kawai, A. Ito, Y. Nakahara, M. Futakuchi, T. Shirai, H. Honda, T. Kobayashi and K. Kohri, “Anticancer Effect of Hyper-thermia on Prostate Cancer Mediated by Magnetite Cationic Liposomes and Immune-Response Induction in Transplanted Syngeneic Rats,” The Prostate, Vol. 64, No. 4, 2005, pp. 373-381. doi:10.1002/pros.20253

[4]   M. Yanase, M. Shinkai, H. Honda, T. Wakabayashi and J. Yoshida, T Kobayashi, “Antitumor Immunity Induction by Intracellular Hyperthermia Using Magnetite Cationic Liposomes,” Cancer Science, Vol. 89, No. 7, 1998, pp. 775-782. doi:10.1111/j.1349-7006.1998.tb03283.x

[5]   M. Shinkai, M. Yanase, H. Honda, T. Wakabayashi, J. Yoshida and T. Kobayashi, “Intracellular Hyperthermia for Cancer Using Magnetite Cationic Liposomes: In Vitro Study,” Cancer Science, Vol. 87, No. 11, 1996, pp. 1179-1183. doi:10.1111/j.1349-7006.1996.tb03129.x

[6]   A. Ménoret and R. Chandawarkar, “Heat-Shock Protein-Based Anticancer Immunotherapy: An Idea Whose Time Has Come,” Seminars in Oncology, Vol. 25, No. 6, 1998, pp. 654-660.

[7]   P. K. Srivastava, A. Ménoret, S. Basu, R. Binder and K. Quade, “Heat Shock Proteins Come of Age: Primitive Functions Acquired New Roles in an Adaptive World,” Immunity, Vol. 8, No. 6, 1998, pp. 657-665. doi:10.1016/S1074-7613(00)80570-1

[8]   Y. Tamura, N. Tsuboi, N. Sato and K. Kikuchi, “70 kDa Heat Shock Cognate Protein Is a Transformation-Associated Antigen and a Possible Target for the Host’s Anti-Tumor Immunity,” The Journal of Immunology, Vol. 151, No. 10, 1993, pp. 5516-5524.

[9]   Y. Tamura, P. Peng, K. Liu, M. Daou and P. K. Srivastava, “Immunotherapy of Tumors with Autologous Tumor-Derived Heat Shock Protein Preparations,” Science, Vol. 278, No. 5335, 1997, pp. 117-120. doi:10.1126/science.278.5335.117

[10]   Y. Tamura and N. Sato, “Heat Shock Proteins: Chaper- oning of Innate and Adaptive Immunities,” Japanese Journal of Hyperthermic Oncology, Vol. 19, No. 3, 2003, pp. 131-139.

[11]   P. K. Srivastava, “Immunotherapy for Human Cancer Using Heat Shock Protein-Peptide Complexes,” Current Oncology Reports, Vol. 7, No. 2, 2005, pp. 104-108. doi:10.1007/s11912-005-0035-8

[12]   Y. Tamura, S. Ta-kashima, J.M. Cho, W. Qi, K. Kamiguchi, T. Torigoe, S. Takahashi, I. Hirai, N. Sato and K. Kikuchi, “Inhibition of Natural Killer Cell Cytotoxicity by Cell Growth-Related Molecules,” Cancer Science, Vol. 87, No. 6, 1996, pp. 623-630. doi:10.1111/j.1349-7006.1996.tb00269.x

[13]   G. Ueda, Y. Tamura, I. Hirai, K. Kamiguchi, S. Ichimiya, T. Torigoe, H. Hiratsuka, H. Sunakawa and N. Sato, “Tumor-Derived Heat Shock Protein 70-Pulsed Dendritic Cells Elicit Tumor-Specific Cytotoxic T Lymphocytes (Ctls) and Tumor Immunity,” Cancer Science, Vol. 95, No. 1, 2004, pp. 248-253. doi:10.1111/j.1349-7006.2004.tb02211.x

[14]   A. Ito, H. Honda and T. Kobayashi, “Cancer Immunotherapy Based on Intracellular Hyperthermia Using Magnetite Nanoparticles: A Novel Concept of ‘Heat-Controlled Necrosis’ with Heat Shock Protein Expression,” Cancer Immunology, Immunotherapy, Vol. 55, No. 3, 2006, pp. 320-328. doi:10.1007/s00262-005-0049-y

[15]   H. Shi, T. Cao, J. E. Connolly, L. Monnet, L. Bennett, S. Chapel, C. Bagnis, P. Mannoni, J. Davoust, A. K. Palucka and J. Banchereau, “Hyperthermia Enhances CTL Cross-Priming,” The Journal of Immunology, Vol. 176, No. 4, 2006, pp. 2134-2141.

[16]   K. Jimbow, T. Iwashina, F. Alena, K. Yamada, J. Pankovich and T. Umemura, “Exploitation of Pigment Biosynthesis Pathway as a Selective Chemotherapeutic Approach for Malignant Melanoma,” Journal of Investigative Dermatology, Vol. 100, No. S2, 1993, pp. S231-S238.

[17]   F. Alena, T. Ishikawa, A. Gili and K. Jimbow, “Selective in Vivo Accumulation of N-acetyl-4-S-Cysteaminylphe- nol in B16F10 Murine Melanoma and Enhancement of Its in Vitro and in Vivo Antimelanoma Effect by Combina- tion of Buthionine Sulfoximine,” Cancer Research, Vol. 54, No. 10, 1994, pp. 2661-2666.

[18]   J. M. Pankovich and K. Jimbow, “Tyrosine Transport in a Human Melanoma Cell Line as a Basis for Selective Transport of Cytotoxic Analogues,” Biochemical Journal, Vol. 280, 1991, pp. 721-725.

[19]   K. Reszka and K. Jimbow, “Electron Do-nor and Accep- tor Properties of Melanin Pigments in the Skin,” In: J. Fuchs and L. Packer, Oxidative Stress in Dermatology, Marcel Dekker Inc., New York, 1993. pp. 287-320.

[20]   M. Tandon, P. D. Thomas, M. Shokravi, S. Singh, S. Samra, D. Chang and K. Jimbow, “Synthesis and Antitumour Effect of the Melanogenesis-Based Anti-Melanoma Agent N-Propionyl-4-S-Cysteaminylphenol,” Biochemical Pharmacology, Vol. 15, No. 12, 1998, pp. 2023- 2029. doi:10.1016/S0006-2952(98)00090-2

[21]   P. D. Thomas, H. Kishi, H. Cao, M. Ota, T. Yamashita, S. Singh and K. Jimbow, “Selective Incorporation and Specific Cytocidal Effect as the Cellular Basis for the Antimelanoma Action of Sulphur Containing Tyrosine Ana- logs,” Journal of Investigative Dermatology, Vol. 113, 1999, pp. 928-934. doi:10.1046/j.1523-1747.1999.00781.x

[22]   J. Dakour, M. Vinayagamoorthy, H. Chen, D. Luo, W. Dixon and K. Jimbow, “Identification of A cDNA for Ca2+-Binding Calnexin-Like Phosphoprotein (p90) on Melanosomes in Normal and Malignant Human Melano- cytes,” Experimental Cell Research, Vol. 209, No. 2, 1993, pp. 288-300. doi:10.1006/excr.1993.1313

[23]   K. Toyofuku, I. Wada, K. Hirosaki, J. S. Park, Y. Hori and K. Jimbow, “Involvement of Calnexin in Maturation of Tyrosinase as a Molecular Chaperone,” Journal of Biochemistry, Vol. 125, 1999, pp. 82-89.

[24]   K. Jimbow, P.F. Gomez, K. Toyofuku, D. Chang, S. Miura, H. Tsujiya and J.S. Park, “Biological Role of Tyrosinase Related Protein and Its Biosynthesis and Transport from TGN to Stage I Mela-nosome, Late Endosome, through Gene Transfection Study,” Pigment Cell Research, Vol. 10, No. 4, 1997, pp. 206-213. doi:10.1111/j.1600-0749.1997.tb00486.x

[25]   K. Jimbow, J. S. Park, F. Kato, K. Hirosaki, K. Toyofuku, C. Hua and T. Yamashita, “Assembly, Target Signal and Intracellular Transport of Tyrosinase Gene Family Protein in the Initial Stage of Melanosome Biogenesis,” Pigment Cell Research, Vol. 13, No. 4, 2000, pp. 222-229. doi:10.1034/j.1600-0749.2000.130403.x

[26]   K. Jimbow, C. Hua, P. F. Gomez, K. Hirosaki, K. Shinoda, T. G. Salopek, H. Matsusaka, H. Y. Jin and T. Yamashita, “Intracellular Vesicular Trafficking of Tyrosinase Gene Family Protein in Eu and Pheomelanosome Biogenesis,” Pigment Cell Research, Vol. 13, No. S8, 2000, pp. S110-S117. doi:10.1034/j.1600-0749.13.s8.20.x

[27]   T. Miura, K. Jimbow and S. Ito, “The in Vivo Antimelanoma Effect of 4-S-Cysteaminylphenol and Its N-Acetyl Derivative,” International Journal of Cancer, Vol. 46, No. 5, 1990, pp. 931-934. doi:10.1002/ijc.2910460530

[28]   M. Tandon, P. D. Thomas, M. Shokravi, S. Singh, S. Samra, D. Chang and K. Jimbow, “Synthesis and Anti- tumour Effect of the Melanogenesis-Based Antimela- noma Agent N-Propionyl-4-S-Cysteaminylphenol,” Bio- chemical Pharmacology, Vol. 55, No. 12, 1998, pp. 2023- 2029. doi:10.1016/S0006-2952(98)00090-2

[29]   S. Ito, T. Kato, K. Ishikawa, T. Kasuga and K. Jimbow, “Mechanism of Selective Toxicity of 4-S-Cysteinylphenol and 4-S-Cysteaminylphenol to Melanocytes,” Biochemical Pharmacology, Vol. 36, No. 12, 1987, pp. 2007-2011. doi:10.1016/0006-2952(87)90501-6

[30]   A. Gili, P. D. Thomas, M. Ota and K. Jimbow, “Comparison of in Vitro Cytotoxicity of N-Acetyl and N-Propionyl Derivatives of Phenolic Thioether Amines in Melanoma and Neuroblastoma Cells and the Relationship to Tyrosinase and Tyrosine Hydroxylase Enzyme Activity,” Melanoma Research, Vol. 10, No. 1, 2000, pp. 9-15.

[31]   B. Thiesen and A. Jordan, “Clinical Applications of Magnetic Nanoparticles for Hyperthermia,” International Journal of Hyperthermia, Vol. 24, No. 6, 2008, pp. 467-474.

[32]   M. Johannsen, U. Gneveckow, L. Eckelt, A. Feussner, N. Wald?fner, R. Scholz, S. Deger, P. Wust, S. A. Loening and A. Jordan, “Clinical Hyperthermia of Prostate Cancer Using Magnetic Nanoparticles: Presentation of a New Interstitial Technique,” International Journal of Hyperthermia, Vol. 21, No. 7, 2005, pp. 637-647.

[33]   A. Ito, M. Fujioka, T. Yoshida, K. Wa-kamatsu, S. Ito, T. Yamashita, K. Jimbow and H. Honda, “4-S-Cysteaminyl-phenol-Loaded Magnetite Cationic Liposomes for Combination Therapy of Hyperthermia with Chemotherapy against Malignant Melanoma,” Cancer Science, Vol. 98, No. 3, 2007, pp. 424-430. doi:10.1111/j.1349-7006.2006.00382.x

[34]   T. Takada, T. Yamashita, M. Sato, A. Sato, I. Ono, Y. Tamura, N. Sato, A. Miyamoto, A. Ito, H. Honda, K. Wakamatsu, S. Ito and K. Jimbow, “Growth Inhibition of Re-Challenge B16 Melanoma Transplant by Conjugates of Melanogenesis Substrate and Magnetite Nanoparticles as the Basis for Developing Melanoma-Targeted Chemo- Ther-mo-Immunotherapy,” Journal of Biomedicine and Bio-technology, 2009, Article ID: 457936. doi:10.1155/2009/457936

[35]   M. Sato, T. Yamashita, M. Ohkura, Y. Osai, A. Sato, T. Takada, H. Matsusaka, I. Ono, Y. Tamura, N. Sato, Y. Sasaki, A. Ito, H. Honda, K. Wakamatsu, S. Ito and K. Jimbow, “N-Propionyl-Cysteaminyl-Phenol-Magnetite Con- jugate (NPrCAP/M) Is a Nanoparticle for the Targeted Growth Suppression of Melanoma Cells,” Journal of Investigative Dermatology, Vol. 129, 2009, pp. 2233-2241. doi:10.1038/jid.2009.39

[36]   M. Suzuki, M. Shinkai, H. Honda and T. Kobayashi, “Anticancer Effect and Immune Induction by Hyperthermia of Malignant Melanoma Using Magnetite Cationic Liposomes,” Melanoma Re-search, Vol. 13, No. 2, 2003, pp. 129-135. doi:10.1097/00008390-200304000-00004

[37]   M. Ya-nase, M. Shinkai, H. Honda, T. Wakabayashi, J. Yoshida and T. Kobayashi, “Intracellular Hyperthermia for Cancer Using Magnetite Cationic Liposomes: An in Vivo Study,” Cancer Science, Vol. 89, No. 4, 1998, pp. 463-469. doi:10.1111/j.1349-7006.1998.tb00586.x

[38]   N. Kawai, A. Ito, Y. Nakahara, M. Futakuchi, T. Shirai, H. Honda, T. Kobayashi and K. Kohri, “Anticancer Effect of Hyper-thermia on Prostate Cancer Mediated by Magnetite Cationic Liposomes and Immunere-Sponse Induction in Transplanted Syngeneic Rats,” Prostate, Vol. 64, No. 4, 2005, pp. 373-381. doi:10.1002/pros.20253

[39]   A. Ito, M. Shinkai, H. Honda and T. Kobayashi, “Medical Application off Unctionalized Magnetic Nanoparticles,” Journal of Bioscience and Bioengineering, Vol. 100, No. 1, 2005, pp. 1-11. doi:10.1263/jbb.100.1

[40]   M. Yanase, M. Shinkai, H. Honda, T. Wakabayashi, J. Yoshida and T. Kobayashi, “Antitumor Immunity Induction by Intracellular Hyperthermia Using Magnetite Cationic Lipo-somes,” Cancer Science, Vol. 89, No. 7, 1998, pp. 775-782. doi:10.1111/j.1349-7006.1998.tb03283.x

[41]   A. Ito, M. Shinkai, H. Honda, T. Wakabayashi, J. Yo- shida and T. Kobayashi, “Augmentation of MHC Class I Antigen Presentation via Heat Shock Protein Expression by Hyperthermia,” Cancer Immunology, Immunotherapy, Vol. 50, No. 10, 2001, pp. 515-522. doi:10.1007/s00262-001-0233-7

[42]   A. Ito, T. Kobayashi and H. Honda, “A Mechanism of Antitumor Immunity Induced by Hyperthermia,” Japanese Journal of Hyper-thermic Oncology, Vol. 21, No. 1, 2005, pp. 1-19.

[43]   A. Ito and K. Takeshi, “Intracellular Hyper-thermia Using Magnetite Nanoparticles: A Novel Method for Hyper- thermia Clinical Applications,” Thermal Medicine, Vol. 24, No. 4, 2008, pp. 113-129. doi:10.3191/thermalmed.24.113

[44]   M. Shinkai, M. Yanase, H. Honda, T. Wakabayashi, J. Yoshida and T. Kobayashi, “Intracellular Hyperthermia for Cancer Using Magnetite Cationic Liposomes: In Vitro Study,” Cancer Science, Vol. 87, No. 11, 1996, pp. 1179-1183. doi:10.1111/j.1349-7006.1996.tb03129.x

[45]   R. Hergt, S. Dutz, R. Mueller and M. Zeisberger, “Magnetite Particle Hyperthermia: Nanoparticle Magnetism and Materials Development for Cancer Therapy,” Journal of Physics: Condensed Matter, Vol. 18, No. 38, 2006, pp. S2919-S2934. doi:10.1088/0953-8984/18/38/S26

[46]   A. Ito, M. Shinkai, H. Honda, K. Yoshikawa, S. Saga, T. Wakabayashi, J. Yoshida and T. Kobayashi, “Heat Shock Protein 70 Expression Induces Antitumor Immunity during Intracellular Hyperthermia Using Magnetite Nanopar- ticles,” Cancer Immunology, Immunotherapy, Vol. 52, No. 2, 2003, pp. 80-88.

[47]   A. Ito, F. Matsuoka, H. Honda and T. Kobayashi, “Antitumor Effects of Combined Therapy of Recombinant Heat Shock Protein 70 and Hyperthermia Using Magnetic Nanoparticles in an Experimental Subcutaneous Murine Melanoma,” Cancer Immunology, Immunotherapy, Vol. 53, No. 1, 2004, pp. 26-32. doi:10.1007/s00262-003-0416-5

[48]   A. Ito, H. Honda and T. Kobayashi, “Cancer Immuno- therapy Based on Intracellular Hyperthermia Using Magnetite Nanoparticles: A Novel Concept of ‘Heat Con- trolled Necrosis’ with Heat Shock Protein Expression,” Cancer Immunology, Immunotherapy, Vol. 55, No. 3, 2006, pp. 320-328.doi:10.1007/s00262-005-0049-y

[49]   P. Manini, A. Napolitano, W. Westerhof, P. A. Riley and M. d’Ischia, “A Reactive Ortho-Quinone Generated by Tyrosinase-Catalyzed Oxidation of the Skin Depigmenting Agent Monobenzone: Self-Coupling and Thiol-Con- jugation Reactions and Possible Implications for Melano-cyte Toxicity,” Chemical Research in Toxicology, Vol. 22, No. 8, 2009, pp. 1398-1405. doi:10.1021/tx900018q

[50]   A. Sato, Y. Tamura, N. Sato, T. Yamashita, T. Takada, M. Sato, Y. Osai, M. Okura, I. Ono, A. Ito, H. Honda, K. Wakamatsu, S. Ito and K. Jimbow, “Melanoma-Targeted Chemo-Thermo-Immuno (CTI)-Therapy Using N-Propionyl-4S-Cysteaminylphenol-Magnetite Nanoparticles Elicits CTL Response via Heat Shock Protein-Peptide Complex Release,” Cancer Science, Vol. 101, No. , 2010, pp. 1939-1946. doi:10.1111/j.1349-7006.2010.01623.x

[51]   K. Jimbow, H. Obata, M. A. Pathak and T. B. Fitzpatrick, “Mechanism of Depigmentation by Hydroquinone,” Journal of Investigative Dermatology, Vol. 62, 1974, pp. 436- 449. doi:10.1111/1523-1747.ep12701679

[52]   J. J. Nordlund, B. Forget, J. Kirkwood and A. B. Lerner, “Dermatitis Produced by Applications of Monobenzone in Patients with Active Vitiligo,” Archives of Dermatology, Vol. 121, No. 9, 1985, pp. 1141-1144. doi:10.1001/archderm.1985.01660090055013

[53]   R. E. Boissy and P. Manga, “On the Etiology of Contact/Occupational Vitiligo,” Pigment Cell Research, Vol. 17, No. 3, 2004, pp. 208-214. doi:10.1111/j.1600-0749.2004.00130.x

[54]   C. J. Cooksey, K. Jimbow, E. J. Land and P. A. Riley, “Reactivity of Orthoquinones Involved in Tyrosi-Nase-Dependent Cy-totoxicity: Differences between Alkylthio- and Al-koxy-Substituents,” Melanoma Research, Vol. 2, No. 5-6, 1992, pp. 283-293. doi:10.1097/00008390-199212000-00001

[55]   Y. Mi-namitsuji, K. Toyofuku, S. Sugiyama and K. Jimbow, “Sulphur Containing Tyrosinase Analogs Can Cause Se-lective Melanocytoxicity Involving Tyrosinase-Mediated Apoptosis,” Journal of Investigative Dermatology, Vol. 4, 1999, pp. S130-S136.

[56]   K. Jimbow, Y. Miyake, K. Homma, K. Yasuda, Y. Izumi, A. Tsutsumi and S. Ito, “Characterization of Melano- genesis and Morphogenesis of Melanosomes by Physicochemical Properties of Melanin and Melanosomes in Malignant Melanoma,” Cancer Research, Vol. 44, No. 3, 1984, pp. 1128-1134.

[57]   P. G. Parsons, F. Favier, M. McEwan, T. Takahashi, K. Jimbow and S. Ito, “Action of Cysteaminylphenols on Human Melanoma Cells in Vivo and in Vitro: 4-S-Cysteaminylphenol Binds Protein Disulphide Isomerise,” Melanoma Research, Vol. 1, No. 2, 1992, pp. 97-104. doi:10.1097/00008390-199106000-00004

[58]   V. Hari-haran, J. Klarquist, M.J. Reust, A. Koshoffer, M.D. McKee, R.E. Boissy and I.C. Le Poole, “Monobenzyl Ether of Hydroquinone and 4-Tertiary Butyl Phenol Activate Markedly Different Physiological Responses in Melanocytes: Relevance to Skin Depigmentation,” Journal of Investigative Dermatology, Vol. 130, 2010, pp. 211-220. doi:10.1038/jid.2009.214

[59]   J. G. van den Boorn, D. I. Picavet, P. F. van Swieten, H. A. van Veen, D. Konijnenberg, P. A. van Veelen, T. van Capel, E. C. Jong, E. A. Reits, J. W. Drijfhout, J. D. Bos, C. J. Melief and R. M. Luiten, “Skin-Depigmenting Agent Monoben-zone Induces Potent T-Cell Autoimmunity toward Pig-mented Cells by Tyrosinase Haptenation and Melanosome Autophagy,” Journal of Investigative Der- matology, Vol. 131, No. 6, 2011, pp. 1240-1251.

[60]   O. J. Finn, “Molecular Origins of Cancer,” New England Journal of Medicine, Vol. 358, 2008, pp. 2704-2711.

[61]   F. S. Hodi, F. Stephen, S. J. O’Day, D. F. McDermott, R. W. Weber, J. A. Sosman, J. B. Haanen, R. Gonzalez, C. Robert, D. Schadendorf, J. C. Hassel, W. Akerley, A. J. M. van den Eertwegh, J. Lutzky, P. Lorigan, J. M. Vaubel, G. P. Linette, D. Hogg, C. H. Ottensmeier, C. Lebbé, C. Peschel, I. Quirt, J. I. Clark, J. D. Wolchok, J. S. Weber, J. Tian, M. J. Yellin, G. M. Nichol, A. Hoos and W. J. Urba, “Improved Survival with Ipilimumab in Patients with Metastatic Melanoma,” New England Journal of Medicine, Vol

[62]   D. J. Schwartzentruber, D. H. Lawson, J. M. Richards, R. M. Conry, D. M. Miller, J. Treisman, F. Gailani, L. Riley, K. Conlon, B. Pockaj, K. L. Kendra, R. L. White, R. Gonzalez, T. M. Kuzel, B. Curti, P. D. Leming, E. D. Whitman, J. Bal-kissoon, D. S. Reintgen, H. Kaufman, F. M. Marincola, M. J. Merino, S. A. Rosenberg, P. Choyke, D. Vena and P. Hwu, “gp100 Peptide Vaccine and Inter- leukin-2 in Patients with Advanced Melanoma,” New England Journal of Medicine, Vol. 364, No. 22, 2011, pp. 2119-2127. doi:10.

[63]   C. Robert, L. Thomas, I. Bondarenko, S. O’Day, J. W. C. Garbe, C. Lebbe, J. F. Baurain, A. Testori, J. J. Grob, N. Davidson, J. Richards, M. Maio, A. Hauschild, W. H. Miller Jr., P. Gascon, M. Lotem, K. Harmankaya, R. Ibra- him, S. Francis, T. Chen, R. Humphrey, A. Hoos and J. D. Wolchok, “Ipilimumab Plus Dacarbazine for Previously Untreated Metastatic Melanoma,” New England Journal of Medicine, Vol. 364, No. 26, 2011, pp. 2517-2526. doi:10.1056/NEJMoa1104621

[64]   P. B. Chapman, A. Hauschild, C. Robert, J. B. Haanen, P. Ascierto, J. Larkin, R. Dummer, C. Garbe, A. Testori, M. Maio, D. Hogg, P. Lorigan, C. Lebbe, T. Jouary, D. Schadendorf, A. Ribas, S. J. O’Day, J. A. Sosman, J. M. Kirkwood, A. M. M. Eggermont, B. Dreno, K. Nolop, J. Li, B. Nelson, J. Hou, R. J. Lee, K. T. Flaherty and G. A. McArthur, “Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation,” New England Journal of Medicine, Vol. 364, No. 26, 2011, pp. 2507- 2516. doi:10.1056/NEJMoa110

[65]   K. Mise, N. Kan, T. Okino, M. Nakanishi, K. Satoh, Y. Teramura, S. Yamasaki, K. Ohgaki and T. Tobe, “Effect of Heat Treatment on Tumor Cells and Antitumor Effector Cells,” Cancer Research, Vol. 50, No. 19, 1990, pp. 6199-6202.

[66]   A. Ito, F. Matsuoka, H. Honda and T. Kobayashi, “Heat Shock Protein 70 Gene Therapy Combined with Hyperthermia Using Magnetic Nanoparticles,” Cancer Gene Therapy, Vol. 10, No. 12, 2003, pp. 918-925. doi:10.1038/sj.cgt.7700648

[67]   M. Yanase, M. Shinkai, H. Honda, T. Wakabayashi, J. Yoshida and T. Kobayashi, “Intracellular Hyperthermia for Cancer Using Magnetite Cationic Liposomes: An in Vivo Study,” Cancer Science, Vol. 89, No. 4, 1998, pp. 463-469. doi:10.1111/j.1349-7006.1998.tb00586.x

 
 
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