title: Enhanced antitumor efficacy of a novel oncolytic adenovirus combined with temozolomide in the treatment of melanoma in vivo.
abstract: OBJECTIVE
  The aim of this study was to investigate the effect of Ki67-ZD55-IL-24 with temozolomide (TMZ) against melanoma in mice.
  
  
  METHODS
  Seventy-eight mice with subcutaneous injection of A375 cells (2 × 10(6)) into the right flank were randomized to receive phosphate buffered saline (PBS), Ki67-ZD55, Ki67-ZD55-IL-24, TMZ, TMZ + Ki67-ZD55, and TMZ + Ki67-ZD55-IL-24. Six mice were killed in each group 10 days after intervention for detecting IL-24 mRNA and protein expression. The remaining mice were monitored to draw the body weight change curve and tumor growth curve, and killed 30 days after intervention. Tumors were excised and weighted. The morphology of tumor tissues was determined by hematoxylin and eosin (HE) staining, and the apoptosis index and rate of apoptotic cells were determined by TUNEL assay and AnnexinV-FITC/PI double staining, respectively.
  
  
  RESULTS
  The Ki67-ZD55-IL-24-treated group generated much more reactive oxygen species than the untreated group. There was no significant difference in IL-24 expression between Ki67-ZD55-IL-24 and TMZ + Ki67-ZD55-IL-24 groups. Immunohistochemical analysis and Western blot revealed that both the Ki67-ZD55 and Ki67-ZD55-IL-24 could significantly reduce the expression of MGMT. Toxicity assessments demonstrated that mice in the three groups that received TMZ exhibited significant body weight loss following treatment. HE staining showed that TMZ + Ki67-ZD55-IL-24 group had much fewer karyokinesis in the tumors, compared with other groups. The apoptosis index of tumor tissues and the rate of apoptotic cells were significantly higher in TMZ + Ki67-ZD55-IL-24 group than in other groups (all P < 0.05).
  
  
  CONCLUSIONS
  These findings indicate this novel strategy holds promising potentials for treatment of malignant melanoma.
authors.affiliation: Department of Dermatology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, Jiangsu Province, China.
authors.forename: Guan
authors.initials: G
authors.lastname: Jiang
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Li
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Wei
authors.forename: Jun-Nian
authors.initials: JN
authors.lastname: Zheng
authors.forename: Yan-Qun
authors.initials: YQ
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005434:Flow Cytometry; D015316:Genetic Therapy; D006801:Humans; D007124:Immunoenzyme Techniques; D007378:Interleukins / Q000235:genetics*; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077204:Temozolomide; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D003606:Dacarbazine; D007378:Interleukins; D019394:Ki-67 Antigen; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins; D000099180:Interleukin-24; C528331:MGMT protein, mouse
references.citation: J Natl Cancer Inst. 2006 Mar 1;98(5):298-300
references.pmid: 16507823
references.citation: Med Oral Patol Oral Cir Bucal. 2013 Mar 01;18(2):e174-9
references.pmid: 23229269
references.citation: Cancer Lett. 2010 Aug 28;294(2):220-8
references.pmid: 20189296
references.citation: Nat Med. 2000 Aug;6(8):879-85
references.pmid: 10932224
references.citation: Hum Gene Ther. 2011 Apr;22(4):389-404
references.pmid: 20939692
references.citation: Tumour Biol. 2013 Apr;34(2):1263-71
references.pmid: 23430584
references.citation: Cancer Gene Ther. 2013 Jan;20(1):38-45
references.pmid: 23175244
references.citation: Cancer Gene Ther. 2006 Nov;13(11):1011-22
references.pmid: 16799468
references.citation: Oncoimmunology. 2013 Feb 1;2(2):e23288
references.pmid: 23525955
references.citation: Eur J Cancer. 2011 Jul;47(10):1476-83
references.pmid: 21600759
references.citation: J Invest Dermatol. 2004 Sep;123(3):583-8
references.pmid: 15304100
references.citation: NMR Biomed. 2013 Jan;26(1):98-105
references.pmid: 22745015
references.citation: J Gene Med. 2005 Oct;7(10):1356-66
references.pmid: 15945123
references.citation: CA Cancer J Clin. 2010 Sep-Oct;60(5):301-16
references.pmid: 20671054
references.citation: Gene Ther. 1999 Jun;6(6):1192-7
references.pmid: 10455425
references.citation: Mol Cancer Ther. 2008 Dec;7(12):3842-51
references.pmid: 19056673
references.citation: Hum Gene Ther. 2005 Jul;16(7):845-58
references.pmid: 16000066
references.citation: PLoS One. 2011;6(8):e24294
references.pmid: 21897876
references.citation: Nat Med. 2000 Oct;6(10):1134-9
references.pmid: 11017145
references.citation: Cell Res. 2006 Nov;16(11):879-86
references.pmid: 17102812
references.citation: Br J Cancer. 2011 Jun 7;104(12):1816-21
references.pmid: 21610711
references.citation: Curr Cancer Drug Targets. 2009 May;9(3):391-7
references.pmid: 19442058
references.citation: BMC Biotechnol. 2006 Aug 03;6:36
references.pmid: 16887042
references.citation: CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30
references.pmid: 16514137
references.citation: Oncol Lett. 2013 Nov;6(5):1289-1294
references.pmid: 24179510
references.citation: CA Cancer J Clin. 2013 Jan;63(1):11-30
references.pmid: 23335087
references.citation: Gene Ther. 2005 Mar;12(5):437-45
references.pmid: 15647767
references.citation: Int Immunopharmacol. 2004 May;4(5):649-67
references.pmid: 15120650
references.citation: PLoS One. 2011;6(11):e27934
references.pmid: 22140489