title: Combination of macrophage inflammatory protein 1 alpha with existing therapies to enhance the antitumor effects on murine hepatoma.
abstract: Existing therapies such as irradiation or sorafenib have limited success in the treatment of hepatocellular carcinoma (HCC) due to tumor recurrence and metastasis. Therefore, combination with other therapeutics is often considered. Macrophage inflammatory protein-1 alpha (MIP-1α) is a member of a family of chemoattractant cytokines that can induce the migration of monocytes, which in turn can play a role in fighting tumors. This study investigated whether intravenous injection of MIP-1α in conjunction with irradiation or sorafenib could enhance the antitumor effects on murine hepatoma. An HCa-I tumor was grown on the right thigh of each C3H/HeN mouse. Mice were then treated with 10 Gy of irradiation, sorafenib, or a combination of MIP-1α with either irradiation or sorafenib, and antitumor and antimetastatic effects were then investigated. To understand the mechanisms, changes in the level of immunological markers were also evaluated. Combination treatment of MIP-1α with irradiation or sorafenib resulted in a significant enhancement of antitumor effects, prevention of lung metastasis and increase in host survival. This was achieved by significantly increasing the levels of the immunological markers: Cluster Differentiation (CD) 8, CD107A and CD11C. We conclude that a combination treatment of MIP-1α with irradiation or sorafenib would be a useful strategy for management of hepatoma.
authors.affiliation: Department of Radiation Oncology, Yonsei University Medical College, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.
authors.forename: Keun-Yeong
authors.initials: KY
authors.lastname: Jeong
authors.affiliation: Department of Radiation Oncology, Yonsei University Medical College, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, Yonsei University Medical College, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Yonsei University Medical College, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea jsseong@yuhs.ac.
authors.forename: Jinsil
authors.initials: J
authors.lastname: Seong
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D054405:Chemokine CCL3 / Q000008:administration & dosage*; D059248:Chemoradiotherapy / Q000379:methods*; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D054405:Chemokine CCL3; D010671:Phenylurea Compounds; D011838:Radiation-Sensitizing Agents; D009536:Niacinamide; D000077157:Sorafenib
keywords: MIP-1α; hepatocellular carcinoma; irradiation; metastasis; sorafenib