The quaternary state of polymerized human hemoglobin regulates oxygenation of breast cancer solid tumors: A theoretical and experimental study

A major constraint in the treatment of cancer is inadequate oxygenation of the tumor mass, which can reduce chemotherapeutic efficacy. We hypothesize that polymerized human hemoglobin (PolyhHb) can be transfused into the systemic circulation to increase solid tumor oxygenation, and improve chemother...

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Published in:PloS one 2018-02, Vol.13 (2), p.e0191275-e0191275
Main Authors: Belcher, Donald A, Ju, Julia A, Baek, Jin Hyen, Yalamanoglu, Ayla, Buehler, Paul W, Gilkes, Daniele M, Palmer, Andre F
Format: Article
Language:English
Subjects:
Analysis
Biology and Life Sciences
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Care and treatment
Chemotherapy
Female
Finite Element Analysis
Hemoglobins
Hemoglobins - chemistry
Hemoglobins - metabolism
Humans
Medicine and Health Sciences
Models, Theoretical
Oxygen - metabolism
Physical Sciences
Polymerization
Protein Structure, Quaternary
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Viscosity
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Summary:A major constraint in the treatment of cancer is inadequate oxygenation of the tumor mass, which can reduce chemotherapeutic efficacy. We hypothesize that polymerized human hemoglobin (PolyhHb) can be transfused into the systemic circulation to increase solid tumor oxygenation, and improve chemotherapeutic outcomes. By locking PolyhHb in the relaxed (R) quaternary state, oxygen (O2) offloading at low O2 tensions (20 mm Hg) is facilitated with tense (T) state PolyhHb. Therefore, R-state PolyhHb may deliver significantly more O2 to hypoxic tissues. Biophysical parameters of T and R-state PolyhHb were used to populate a modified Krogh tissue cylinder model to assess O2 transport in a tumor. In general, we found that increasing the volume of transfused PolyhHb decreased the apparent viscosity of blood in the arteriole. In addition, we found that PolyhHb transfusion decreased the wall shear stress at large arteriole diameters (>20 μm), but increased wall shear stress for small arteriole diameters (
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0191275