Koichi Rikimaru

Evaluation of serum concentration of parathyroid hormone-related protein and its implication in hypercalcemia in squamous cell carcinoma of the head and neck

Hypercalcemia is a common and serious complication associated with squamous cell carcinoma (SCC) and is considered to be caused by a tumor-derived factor, parathyroid hormone-related protein (PTHrP). However, the correlation between serum levels of calcium and PTHrP and the kinetics of PTHrP in SCC of the head and neck is unknown, because the behavior of the circulating form of PTHrP in patients has not been determined. In the present study, the PTHrP concentrations in serum samples from 54 patients (37 with SCC and 17 with benign tumors) were measured by a recently developed radioimmunoassay directed toward the C-terminal region of PTHrP, and the laboratory data including those calcium levels in corresponding samples were reviewed retrospectively. Results showed hypercalcemia in four patients with advanced cancer and in whom elevation of the serum PTHrP concentration was observed simultaneously. The regression analysis also revealed the linear relationship of the calcium level to the PTHrP concentration, but not to the concentration of phosphorus or creatinine, suggesting that monitoring of serum PTHrP level is useful for prediction of hypercalcemia associated with head and neck cancer.

Simultaneous production of G- and M-CSF by an oral cancer cell line and the synergistic effects on associated leucocytosis

We established a novel cell line, TSU, from a oral cancer patient with marked leucocytosis. The culture supernatant of TSU cells promoted granulocytic colony formation by mouse bone marrow cells, indicating that TSU produced granulocyte-colony stimulating factor (G-CSF). The concentration of G-CSF was 2.45 micrograms/mg protein, measured by enzyme-linked immunosorbent assay (ELISA). The maximum number of colonies induced by TSU culture supernatant was more than that achieved with recombinant human G-CSF (rhG-CSF) and the size of the colonies induced by TSU supernatant was obviously larger than those achieved with rhG-CSF. The activity of TSU supernatant was completely inhibited by antihuman G-CSF and macrophage-colony stimulating factor (M-CSF) antibodies, but was only partially inhibited by antihuman G- or M-CSF antibody alone. These results indicate that not only G-CSF but also M-CSF, both of which could be produced by TSU cells, are involved in causing leucocytosis; the results suggest that the synergistic production of G- and M-CSF could play an important role in the leucocytosis associated with oral cancer.