title: Influence of PEG-conjugated hemoglobin on tumor oxygenation and response to chemotherapy.
abstract: Hypoxic tumors are significantly more malignant, metastatic, radio- and chemoresistant. The use of artificial oxygen carriers represents a new approach to the problem of hypoxia. In the present study, female athymic BALB/c nude mice bearing the cervical carcinoma were untreated or treated with cisplatin to determine whether administration of artificial oxygen carrier (PEG-conjugated Hemoglobin, PEG-Hb) could improve the tumor oxygenation and enhance the anti-tumor efficacy of cisplatin. Pimonidazole staining was employed to detect tumor tissue oxygenation status. We found that the application of a higher dose (0.6 g/kg) PEG-Hb could significantly ameliorate the hypoxic condition in cervical carcinoma xenograft models. Co-administration of PEG-Hb (0.6 g/kg) with cisplatin produced significant tumor growth inhibition and pro-apoptotic and anti-proliferative effects as compared to cisplatin alone. These suggest the evaluated PEG-Hb in this experiment has positive effects on cisplatin or cisplatin-based chemotherapy, and further work to optimize its application is warranted.
authors.affiliation: Institute of Microcirculation, Peking Union Medical College & Chinese Academy of Medical Sciences, 5 Dong Dan San Tiao, Beijing, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Yu
authors.forename: Jianqun
authors.initials: J
authors.lastname: Han
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.forename: Peilin
authors.initials: P
authors.lastname: Cui
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Xiu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001802:Blood Substitutes / Q000008:administration & dosage* / Q000494:pharmacology; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D006454:Hemoglobins / Q000008:administration & dosage* / Q000494:pharmacology; D000860:Hypoxia / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009593:Nitroimidazoles; D010101:Oxygen Consumption / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D009593:Nitroimidazoles; C109960:PEG-hemoglobin; D011092:Polyethylene Glycols; C033815:pimonidazole; D002945:Cisplatin