Hemoglobin plays an important role in most vertebrates for gaseous exchange between the vascular system and tissue. It is responsible for carrying oxygen from the respiratory system to the body cells via blood circulation and also carrying the metabolic waste product carbon dioxide away from body cells to the respiratory system, where the carbon dioxide is exhaled. Since hemoglobin has this oxygen transport feature, it can be used as a potent oxygen supplier if it can be stabilized ex vivo and used in vivo.
Naturally-occurring hemoglobin is a tetramer which is generally stable when present within red blood cells. However, when naturally-occurring hemoglobin is removed from red blood cells, it becomes unstable in plasma and splits into two α-β dimers. Each of these dimers is approximately 32 kDa in molecular weight. These dimers may cause substantial renal injury when filtered through the kidneys and excreted. The breakdown of the tetramer linkage also negatively impacts the sustainability of the functional hemoglobin in circulation.
In order to solve the problem, recent developments in hemoglobin processing have incorporated various cross-linking techniques to create intramolecular bonds within the tetramer as well as intermolecular bonds between the tetramers to form polymeric hemoglobin.
Hypoxia is common in cancers. Hypoxia can lead to ionizing radiation and chemotherapy resistance by depriving tumor cells of the oxygen essential for the cytotoxic activities of these agents. Hypoxia may also reduce tumor sensitivity to radiation therapy and chemotherapy through one or more indirect mechanisms that include proteomic and genomic changes. Therefore, there is a need for improved cancer-treatment compositions, particularly, improved cancer-treatment compositions that enhance the efficacy of cytotoxic agents.
Although tumor metastasis causes about 90 percent of cancer deaths, the exact mechanism that allows cancer cells to spread from on part of the body to another is not well understood. So, the improved cancer-treatment compositions that prevent the cancer recurrence is important.
Many recent studies have shown that cancer stem cells (CSCs) play an important role in cancer and tumor development. Wang and Dick (2005) revisited the self-renewal and tumor cell proliferating potentials of leukemia stem cells found in tumor by the stochastic model and cancer stem cell model proposed earlier. According to the stochastic model, there is generally one class of tumor cells which are functionally homogeneous, and the genetic changes can lead to malignancy progression in all these tumor cells. In contrast, the cancer stem cell model proposes that a rare population of cells which have a distinct ability to consistently initiate tumor growth and are able to reproduce a hierarchy of functionally heterogeneous classes of cells may have different tumorigenic pathways compared with the majority of the cells in a tumor. The tumor-initiating cells proposed in the cancer stem cell model can be progressively identified and purified from the rest of the cells. These cells are called cancer stem cells (CSCs). Like leukemia stem cells, other cancers such as breast cancer appear to be driven by the rare population of tumor-initiating cells. Two phenotypes of cells have been identified in breast cancer where one minority phenotype is able to form mammary tumors while another phenotype is not. In brain cancer, two types of cells are found: CD 133+ cells possess differentiative, self-renewal, and tumor-initiating abilities in vivo whereas CD133− cells cannot. More and more evidences have been found to support that these cancer stem cells may be at the apex of all neoplastic systems, and thereby become a new target for cancer treatment. A review article (Mohyeldin et al., 2010) suggested that cancer stem cell niches have much lower oxygen tension. A hypoxic niche is found to be located further away from vasculature of a tumor and contains cancer stem cells which differentially respond to hypoxia with distinct HIF (Hypoxia-inducible factors) induction patterns, in particular HIF-2α. It becomes a new target in the signaling pathways that regulate cancer stem cell self-renewal, proliferation, and survival, and the inhibition of which will attenuate their tumor initiation potential.
Thus there is a need in the art for a composition that can provide high oxygen tension in cancer stem cells. Such a composition could be used to produce oxidative stress or shocks which leads to DNA damage and subsequent DNA damage induced apoptosis in the cancer stem cells.