Polymerized human hemoglobin facilitated modulation of tumor oxygenation is dependent on tumor oxygenation status and oxygen affinity of the hemoglobin-based oxygen carrier
| Autor: | Pedro Cabrales, Andre F. Palmer, Donald A. Belcher, Alfredo Lucas |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer microenvironment Infusions Erythrocytes Skin Neoplasms Cancer therapy Polymers chemistry.chemical_element lcsh:Medicine Pharmacology Oxygen affinity Oxygen Article Polymerization 03 medical and health sciences Mice Hemoglobins 0302 clinical medicine Tumor Microenvironment Potency Skin cancer Animals Humans Tumor growth Computational analysis Infusions Intravenous lcsh:Science Melanoma Cancer Multidisciplinary Chemistry Microcirculation lcsh:R Hematology Blood flow Tumor Oxygenation Xenograft Model Antitumor Assays Cell Hypoxia Molecular Weight 030104 developmental biology 030220 oncology & carcinogenesis Cancer imaging Female lcsh:Q Hemoglobin Intravenous |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) Scientific reports, vol 10, iss 1 Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-68190-0 |
| Popis: | Administration of hemoglobin-based oxygen carriers (HBOCs) into the systemic circulation is a potential strategy to relieve solid tumor hypoxia in order to increase the effectiveness of chemotherapeutics. Previous computational analysis indicated that the oxygen (O2) status of the tumor and HBOC O2 affinity may play a role in increased O2 delivery to the tumor. However, no study has experimentally investigated how low- and high-affinity HBOCs would perform in normoxic and hypoxic tumors. In this study, we examined how the HBOC, polymerized human hemoglobin (PolyhHb), in the relaxed (R) or tense (T) quaternary state modulates O2 delivery to hypoxic (FME) and normoxic (LOX) human melanoma xenografts in a murine window chamber model. We examined microcirculatory fluid flow via video shearing optical microscopy, and O2 distributions via phosphorescence quenching microscopy. Additionally, we examined how weekly infusion of a 20% top-load dose of PolyhHb influences growth rate, vascularization, and regional blood flow in the FME and LOX tumor xenografts. Infusion of low-affinity T-state PolyhHb led to increased tissue oxygenation, decreased blood flow, decreased tumor growth, and decreased vascularization in hypoxic tumors. However, infusion of both T-state and R-state PolyhHbs led to worse outcomes in normoxic tumors. Of particular concern was the high-affinity R-state PolyhHb, which led to no improvement in hypoxic tumors and significantly worsened outcomes in normoxic tumors. Taken together, the results of this study indicate that the tumor O2 status is a primary determinant of the potency and outcomes of infused PolyhHb. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |