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Measuring Deformability and Red Cell Heterogeneity in Blood by Ektacytometry

Decreased red cell deformability is characteristic of several disorders. In some cases, the extent of defective deformability can predict severity of ...

National Institute Of Diabetes And Digestive And Kidney Diseases

Because 5-year survival rates for patients with metastatic melanoma remain below 25%, there is continued need for new therapeutic approaches. For some tumors, pharmacologic ascorbate treatment may have a beneficial antitumor effect and may work synergistically with standard chemotherapeutics. To investigate this possibility in melanoma, we examined the effect of pharmacologic ascorbate on B16-F10 cells. Murine models were employed to compare tumor size following treatment with ascorbate, and the chemotherapeutic agents dacarbazine or valproic acid, alone or in combination with ascorbate. Results indicated that nearly all melanoma cell lines were susceptible to ascorbate-mediated cytotoxicity. Compared to saline controls, pharmacologic ascorbate decreased tumor size in both C57BL/6 (P < 0.0001) and NOD-scid tumor bearing mice (P < 0.0001). Pharmacologic ascorbate was superior or equivalent to dacarbazine as an antitumor agent. Synergy was not apparent when ascorbate was combined with either dacarbazine or valproic acid; the latter combination may have additional toxicities. Pharmacologic ascorbate induced DNA damage in melanoma cells, as evidenced by increased phosphorylation of the histone variant, H2A.X. Differences were not evident in tumor samples from C57BL/6 mice treated with pharmacologic ascorbate compared to tumors from saline-treated controls. Together, these results suggest that pharmacologic ascorbate has a cytotoxic effect against melanoma that is largely independent of lymphocytic immune functions and that continued investigation of pharmacologic ascorbate in cancer treatment is warranted.

Antitumor effect of pharmacologic ascorbate in the B16 murine melanoma model.

Breaking down, starting up: can a vitamin C-enriched gelatin supplement before exercise increase collagen synthesis?

Despite historical controversy, pharmacologic ascorbate is emerging as promising cancer therapy via pro-oxidant chemistry. In this issue of Cancer Cell, Schoenfeld et al. describe how intracellular iron pools and reactive oxygen species drive pharmacologic ascorbate's selective toxicity to cancer cells in vitro, in mice, and in humans.

Data Triumph at C.

Decreased erythrocyte deformability, as measured by ektacytometry, may be associated with disease severity in sickle cell anemia (SCA). Heterogeneous populations of rigid and deformable cells in SCA blood result in distortions of diffraction pattern measurements that correlate with the concentration of hemoglobin S (HbS) and the percentage of irreversibly sickled cells. We hypothesize that red cell heterogeneity, as well as deformability, will also be influenced by the concentration of alternative hemoglobins such as fetal hemoglobin (HbF) and the adult variant, HbA2. To test this hypothesis, we investigate the relationship between diffraction pattern distortion, osmotic gradient ektacytometry parameters, and the hemoglobin composition of SCA blood. We observe a correlation between the extent of diffraction pattern distortions and percentage of HbF and HbA2. Osmotic gradient ektacytometry data indicate that minimum elongation in the hypotonic region is positively correlated with HbF, as is the osmolality at which it occurs. The osmolality at both minimum and maximum elongation is inversely correlated with HbS and HbA2. These data suggest that HbF may effectively improve surface-to-volume ratio and osmotic fragility in SCA erythrocytes. HbA2 may be relatively ineffective in improving these characteristics or cellular hydration at the levels found in this patient cohort.

Pierre-Christian Violet

Molecular and Clinical Nutrition Section,
Digestive Diseases Branch,
Molecular and Clinical Nutrition Section, Digestive Diseases Branch

National Institute Of Diabetes And Digestive And Kidney Diseases

Measuring Deformability and Red Cell Heterogeneity in Blood by Ektacytometry

Pierre-Christian Violet

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Molecular and Clinical Nutrition Section,Digestive Diseases Branch,Molecular and Clinical Nutrition Section, Digestive Diseases Branch

National Institute Of Diabetes And Digestive And Kidney Diseases

Measuring Deformability and Red Cell Heterogeneity in Blood by Ektacytometry

Molecular and Clinical Nutrition Section,
Digestive Diseases Branch,
Molecular and Clinical Nutrition Section, Digestive Diseases Branch