Kohji Iida

Clinical significance of interleukin-1 receptor antagonist in patients with cervical carcinoma

OBJECTIVE Our purpose was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1ra), which is an endogenous inhibitor cytokine of IL-1, in patients with cervical carcinoma. METHODS Tissue IL-1ra expression and serum IL-1ra level were examined by enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry in normal controls and patients with cervical carcinoma. RESULTS Tissue IL-1ra protein level by ELISA was significantly higher in squamous cell carcinoma (n = 9) than in the normal cervix (n = 7) and adenocarcinoma (n = 3). Western blotting confirmed the main presence of intracellular IL-1ra type 1 in squamous cell carcinoma. Immunohistochemistry demonstrated significant IL-1ra expression only in tumor cells of squamous cell carcinoma. Elevation of serum IL-1ra level was found in patients with squamous cell carcinoma (n = 38) compared to normal women (n = 13), but not in patients with adenocarcinoma (n = 9). Although serum IL-1ra level did not correlate with clinical stage or any other tumor marker, high serum IL-1ra level was associated with pelvic lymph node metastasis and poor prognosis in patients with squamous cell carcinoma. On the other hand, these results were not obtained in patients with cervical adenocarcinoma. CONCLUSION IL-1ra may play important roles in local and general malignant behaviors in patients with cervical squamous cell carcinoma, and measurement of serum IL-1ra level may be useful in predicting patient survival.

Dihydropyrimidine dehydrogenase in normal and malignant endometrium: relationship with cell proliferation and thymidine phosphorylase.

Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine salvage enzyme responsible for degradation of thymine, which is produced from thymidine by thymidine phosphorylase (TP). Our purpose was to determine the relationship between DPD, cell proliferation and TP expression in human endometrium. We examined DPD gene expression using reverse transcription-polymerase chain reaction, DPD protein levels using enzyme-linked immunosorbent assay, and DPD protein localization using immunohistochemistry in 58 normal endometria and 28 endometrial cancers. DPD gene expression was then related to the proliferating cell nuclear antigen index and to TP gene expression. DPD gene expression, which was correlated with DPD protein level, was relatively stable throughout various menstrual phases but was significantly elevated in postmenopausal status. It was significantly lower in endometrial cancer than in normal endometrium. Localization analysis revealed that DPD protein was located primarily in epithelial cells, but was also present in stromal cells. DPD gene expression correlated inversely with the PCNA index. TP gene expression pattern contrasted with that of DPD in postmenopausal and malignant endometrium. A high ratio of TP to DPD gene expression was significantly more frequent in endometrial cancer than in normal endometrium in any menstrual phase. DPD may act cooperatively with TP to affect cell function by maintaining the pyrimidine nucleotide pool balance in normal and malignant endometrium.